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12,100 | 26,687,844 | There was no evidence of a difference in terms of median survival time in the trial comparing GM-CSF and antibiotics . | BACKGROUND Febrile neutropenia ( FN ) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer , with a mortality rate of 2 % to 21 % .
The two main types of prophylactic regimens are granulocyte ( macrophage ) colony-stimulating factors ( G(M)-CSF ) and antibiotics , frequently quinolones or cotrimoxazole .
Current guidelines recommend the use of colony-stimulating factors when the risk of febrile neutropenia is above 20 % , but they do not mention the use of antibiotics .
However , both regimens have been shown to reduce the incidence of infections .
Since no systematic review has compared the two regimens , a systematic review was undertaken .
OBJECTIVES To compare the efficacy and safety of G(M)-CSF compared to antibiotics in cancer patients receiving myelotoxic chemotherapy . | Introduction Recombinant granulocyte colony-stimulating factor ( G-CSF ) may aid engraftment post high-dose chemo-/radiotherapy in patients with haematological malignancies undergoing allogeneic bone marrow transplantation ( BMT ) ; however , the effects of G-CSF on graft-versus-host disease ( GvHD ) , relapse , and survival are not well defined . Methods In this double-blind , r and omized , placebo-controlled , multicentre , phase 3 study , the effects of the G-CSF Filgrastim on neutrophil and platelet recovery , and on clinical outcomes were evaluated . Patients ( 12–55 years ) receiving an allogeneic BMT for a haematological malignancy were r and omized to receive Filgrastim 5 µg/kg or placebo . Study treatment was continued until patients achieved an absolute neutrophil count ( ANC ) ≥0.5 × 109/L , or until day 42 . Results Fifty-one patients ( Filgrastim , N = 25 ; placebo , N = 26 ) were evaluable . Patients treated with Filgrastim had significantly faster engraftment with ANC ≥0.5 × 109/L being achieved after a median ( range ) of 15.0 ( 1.0–22.0 ) days vs. 19.0 ( 15.0–28.0 ) days for placebo ( P < 0.0001 ) . The incidence of GvHD was comparable for both groups . During the limited follow-up ( 2 years ) , Filgrastim had no adverse effect on mortality and possibly reduced the rate of relapse Purpose Pegfilgrastim is a pegylated form of filgrastim , a recombinant protein of granulocyte colony-stimulating factor , that is used to reduce the risk of febrile neutropenia ( FN ) . Here , we report the results of a phase III trial of pegfilgrastim in breast cancer patients receiving docetaxel and cyclophosphamide ( TC ) chemotherapy . Methods We conducted a double-blind , placebo-controlled , r and omized trial to determine the efficacy of pegfilgrastim in reducing the risk of FN in early-stage breast cancer patients . A total of 351 women ( 177 in the pegfilgrastim group and 174 in the placebo group ) between 20 and 69 years of age with stage I – III invasive breast carcinoma who were to receive TC chemotherapy ( docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 every 3 weeks ) as either neoadjuvant or adjuvant therapy were enrolled ; 346 of these patients were treated with either pegfilgrastim ( n = 173 ) or placebo ( n = 173 ) . Results The incidence of FN was significantly lower in the pegfilgrastim group than in the placebo group ( 1.2 vs. 68.8 % , respectively ; P < 0.001 ) . In addition , patients in the pegfilgrastim group required less hospitalization and antibiotics for FN . Most adverse events were consistent with those expected for breast cancer subjects receiving TC chemotherapy . Conclusions Pegfilgrastim is safe and significantly reduces the incidence of FN in breast cancer patients Recombinant human granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) shortens the time to neutrophil recovery after intensive chemotherapy , but its role in the treatment of adults with acute lymphoblastic leukemia ( ALL ) is uncertain . We r and omly assigned 198 adults with untreated ALL ( median age , 35 years ; range , 16 to 83 ) to receive either placebo or G-CSF ( 5 microgram/kg/d ) subcutaneously , beginning 4 days after starting intensive remission induction chemotherapy and continuing until the neutrophil count was > /=1 , 000/microL for 2 days . The study assignment was unblinded as individual patients achieved a complete remission ( CR ) . Patients initially assigned to G-CSF then continued to receive G-CSF through 2 monthly courses of consolidation therapy . Patients assigned to placebo received no further study drug . The median time to recover neutrophils > /=1,000/microL during the remission induction course was 16 days ( interquartile range [ IQR ] , 15 to 18 days ) for the patients assigned to receive G-CSF and 22 days ( IQR , 19 to 29 days ) for the patients assigned to placebo ( P < .001 ) . Patients in the G-CSF group had significantly shorter duration s of neutropenia ( < 1 , 000/microL ) and thrombocytopenia ( < 50,000/microL ) and fewer days in the hospital ( median , 22 days v 28 days ; P = .02 ) compared with patients receiving placebo . The patients assigned to receive G-CSF had a higher CR rate and fewer deaths during remission induction than did those receiving placebo ( P = .04 by the chi-square test for trend ) . During Courses IIA and IIB of consolidation treatment , patients in the G-CSF group had significantly more rapid recovery of neutrophils > /=1,000/microL than did the control group by approximately 6 to 9 days . However , the patients in the G-CSF group did not complete the planned first 3 months of chemotherapy any more rapidly than did the patients in the placebo group . Overall toxicity was not lessened by the use of G-CSF . After a median follow-up of 4 . 7 years , there were no significant differences in either the disease-free survival ( P = .53 ) or the overall survival ( P = .25 ) for the patients assigned to G-CSF ( medians , 2.3 years and 2.4 years , respectively ) compared with those assigned to placebo ( medians , 1.7 and 1.8 years , respectively ) . Adults who received intensive chemotherapy for ALL benefited from G-CSF treatment , but its use did not markedly affect the ultimate outcome Patients with non-myeloid hematologic malignancies ( including Hodgkin 's and non-Hodgkin 's lymphomas , myeloma and acute lymphoid leukemia ) or solid tumors underwent cytoreductive conditioning regimens followed by either autologous bone marrow transplantation ( ABMT ) ( n = 343 ) or transplantation of peripheral blood stem cells ( PBSC ) with ( n = 44 ) or without bone marrow ( BM ) ( n = 16 ) . In a r and omized double-blind phase III multi-center trial , patients received either granulocyte-macrophage colony-stimulating factor ( GM-CSF , 10 micrograms/kg/day ) or placebo by daily i.v . infusion beginning 24 h after bone marrow infusion and continuing until the absolute neutrophil count ( ANC ) had recovered to > or = 1000/mm3 , or for a maximum of 30 days . Median time to neutrophil recovery was significantly shorter in the GM-CSF group ( 18 vs 27 days , P < 0.001 ) , and more GM-CSF patients had neutrophil recovery by day 30 ( 70 vs 48 % ) . Median duration of hospitalization was significantly shorter in the GM-CSF group ( 29 vs 32 days , P = 0.02 ) . GM-CSF significantly reduced the median time to neutrophil recovery in patients receiving bone marrow only ( 19 vs 27 days , P < 0.001 ) or PBSC with or without bone marrow ( 14 vs 21 days , P < 0.001 ) . The overall incidence of adverse events was comparable in the two groups , although more patients in the GM-CSF group discontinued treatment due to adverse events ( 17 vs 9 % , P < 0.001 ) . No difference was noted in infection incidence or time to platelet independence . GM-CSF had no negative impact on time to relapse or long-term survival . These data indicate the positive influence of GM-CSF on neutrophil recovery and hospital stay in patients receiving ABMT for a variety of clinical indications BACKGROUND Neutropenia is common in patients receiving myelotoxic chemotherapy . Pegfilgrastim , a sustained- duration filgrastim is a once-per-cycle therapy for prophylactic neutrophil support . PATIENTS AND METHODS Women , treated with four cycles of doxorubicin/docetaxel chemotherapy every 21 days , received pegfilgrastim or filgrastim 24 h after chemotherapy as a single subcutaneous injection per chemotherapy cycle ( pegfilgrastim 30 , 60 or 100 microg/kg ) or daily subcutaneous injections ( filgrastim 5 microg/kg/day ) . Safety , efficacy and pharmacokinetics were analyzed . RESULTS The incidence of grade 4 neutropenia in cycle 1 was 95 , 90 and 74 % , in patients who received pegfilgrastim 30 , 60 and 100 microg/kg , respectively , and 76 % in patients who received filgrastim . Mean duration of grade 4 neutropenia in cycle 1 was 2.7,2 and 1.3 days for doses of pegfilgrastim , and 1.6 days for filgrastim . The pharmacokinetics of pegfilgrastim were non-linear and dependent on both dose and neutrophil count . Pegfilgrastim serum concentration was sustained until the neutrophil nadir occurred then declined rapidly as neutrophils started to recover , consistent with a self-regulating neutrophil-mediated clearance mechanism . The safety profiles of pegfilgrastim and filgrastim were similar . CONCLUSIONS A single subcutaneous injection of pegfilgrastim 100 microg/kg provided neutrophil support and a safety profile comparable to daily subcutaneous injections of filgrastim during multiple chemotherapy cycles In order to evaluate the potential clinical and economic benefits of granulocyte colony-stimulating factor ( G-CSF , filgrastim ) following peripheral blood progenitor cells ( PBPC ) rescue after high-dose chemotherapy ( HDCT ) , 23 consecutive patients aged less than 60 years with poor-prognosis , high- grade non-Hodgkin 's lymphoma ( NHL ) were entered into a prospect i ve r and omized trial between May 1993 and September 1995 . Patients were r and omized to receive either PBPC alone ( n = 12 ) or PBPC+G-CSF ( n = 11 ) after HDCT with busulphan and cyclophosphamide . G-CSF ( 300 microg day[-1 ] ) was given from day + 5 until recovery of granulocyte count to greater than 1.0 x 10(9 ) l(-1 ) for 2 consecutive days . The mean time to achieve a granulocyte count > 0.5 x 10(9 ) l(-1 ) was significantly shorter in the G-CSF arm ( 9.7 vs 13.2 days ; P<0.0001 ) as was the median duration of hospital stay ( 12 vs 15 days ; P = 0.001 ) . In addition the recovery periods ( range 9 - 12 vs 11 - 17 days to achieve a count of 1.0 x 10(9 ) l[-1 ] ) and hospital stays ( range 11 - 14 vs 13 - 22 days ) were significantly less variable in patients receiving G-CSF in whom the values clustered around the median . There were no statistically significant differences between the study arms in terms of days of fever , documented episodes of bacteraemia , antimicrobial drug usage and platelet/red cell transfusion requirements . Taking into account the costs of total occupied-bed days , drugs , growth factor usage and haematological support , the mean expenditure per inpatient stay was pound sterling 6500 ( range pound sterling 5465-pound sterling 8101 ) in the G-CSF group compared with pound sterling 8316 ( range pound sterling 5953-pound sterling 15,801 ) in the group not receiving G-CSF , with an observed mean saving of 1816 per patient ( or 22 % of the total cost ) in the G-CSF group . This study suggests that after HDCT and PBPC rescue , the use of G-CSF leads to more rapid haematological recovery periods and is associated with a more predictable and shorter hospital stay . Furthermore , and despite the additional costs for G-CSF , these clinical benefits are not translated into increased health care expenditure BACKGROUND Immunological and clinical effects of post-transplant growth factor administration have not been well studied . This report describes the outcome and immune functions of a total of 50 HLA-matched related donor allogeneic blood stem-cell transplantation patients who received post-transplant G-CSF ( 10 microg/kg ) or placebo . METHODS Immune status , including number of lymphocyte subsets and their functions , and serum immunoglobulin levels and clinical status -- including GvHD , rate of relapse , event-free survival , and overall survival -- were determined in the patients enrolled in this study . RESULTS Twenty-eight patients survived 1 year after transplant , and 15 patients had available results to compare immune function by r and omization assignment . At 12 months post-transplant , immune parameters in G-CSF versus placebo groups showed no statistically significant differences in number of circulating lymphocyte subsets CD3 , CD4 , CD8 , CD19 and CD56 in the two groups . There was no significant ( NS ) difference in immunoglobulin IgG , IgA and IgM levels , NK or LAK cell-mediated cytotoxicity levels , and mitogen-induced proliferation between post-transplant G-CSF and placebo group . In addition , the analyses of immune parameters at earlier time-points on Days 28 , 100 , 180 , and 270 revealed that , except for LAK cytotoxicity at Day 100 , there was no differences between the two groups . Fourteen of 26 patients are alive in the G-CSF arm and nine of 24 in the placebo arm . Median follow-up of surviving patients is 43 months . Four year overall and event-free survival in the G-CSF and the placebo group were 53 % and 35 % ( NS ) , and 44 % and 36 % ( NS ) respectively . Bacterial or fungal infections were the cause of six of 12 deaths in the G-CSF arm ( all bacterial ) and of four of 15 deaths in the placebo arm ( two deaths from Aspergillus ) ( P=0.26 ) . Two patients relapsed in the G-CSF arm and three in the placebo arm . Four year cumulative incidences of relapse were 8 % versus 13 % in G-CSF versus placebo arms , respectively , ( NS ) . Chronic GvHD developed in 14 of 19 100-day survivors after G-CSF ( 11 extensive stage ) , and in 17 of 20 ( 14 extensive stage ) in the placebo arm . The 4-year cumulative incidence of chronic GvHD was 56 % [ 95 % confidence interval ( CI ) 24 - 88 % ] after G-CSF and 71 % ( 95 % CI 48 - 94 % ) after placebo ; this difference was not statistically significant ( log rank P=0.41 ) . CONCLUSION In summary , there were no significant immunological or alterations in clinical benefit of post-transplant G-CSF administration in T-replete allotransplant recipients Summary : A phase III , r and omized , double-blind , placebo-controlled , multi-center trial was conducted in order to compare the incidence of microbiologically defined infections occurring after high-dose chemotherapy ( HDT ) and ASCT in 98 patients given lenograstim ( Granocyte ® ) and 94 patients given placebo after transplantation . Hematopoietic recovery , the use of i.v . antibiotics , the numbers of red blood cell and platelet transfusions , the days spent in hospital , and the days on parenteral nutrition were also compared . The incidence of infections until neutrophil recovery was significantly less in patients who received lenograstim after HDT and ASCT as compared to patients who received placebo ( 66 of 98 vs 86 of 94 patients , P<0.001 ) . Lenograstim also significantly reduced the use of i.v . antibiotics ( P<0.001 ) and the median duration of i.v . antibiotic treatment ( 8 days vs 10 days , P=0.04 ) , improved neutrophil recovery ( absolute neutrophil count > 0.5 × 109/l : 11 days vs 15 days , P<0.001 ) and reduced the number of days spent in hospital ( 15 days vs 17 days , P<0.001 ) . The administration of lenograstim after HDT and ASCT significantly reduces the incidence of microbiologically defined infections until neutrophil recovery . It also leads to less use of antibiotics and earlier discharge from hospital PURPOSE The aim of this prospect i ve r and omized trial was to examine the efficacy and safety of filgrastim after high-dose chemotherapy and autologous bone marrow transplantation ( ABMT ) . PATIENTS AND METHODS Patients with poor-risk non-Hodgkin 's lymphoma or relapsed Hodgkin 's disease were treated in a r and omized , open-label trial to study the use of filgrastim as an adjunct to high-dose chemotherapy and ABMT . Of 43 assessable patients , 19 were r and omized to receive filgrastim by continuous subcutaneous infusion at a dose of 10 micrograms/kg/d , 10 to filgrastim 20 micrograms/kg/d , and 14 to a parallel control group that received no filgrastim after ABMT . RESULTS For all filgrastim-treated patients analyzed together , the median time to neutrophil recovery > or = 0.5 x 10(9)/L after the day of ABMT was significantly accelerated to 10 days compared with 18 days in control patients ( P = .0001 ) . The median number of platelet transfusions was identical in both groups . Clinical parameters , including the median number of days with fever ( 1 v 4 , P = .0418 ) and neutropenic fever ( 5 v 13.5 , P = .0001 ) were significantly shorter in the filgrastim than in the control group . The number of days on intravenous antibiotics and duration of hospitalization were also shorter in the treated groups ; however , the differences did not reach statistical significance . For patients treated with the two different dose levels of filgrastim , the neutrophil recovery and clinical results were similar . Filgrastim-associated toxicity appeared to be minimal , with five adverse events considered at least possibly related to filgrastim : two in the higher-dose group and three in the lower-dose group . All of these were rated moderate , except one case of severe bone pain that did not preclude continued filgrastim treatment at a lower dose . Survival and relapse-free survival were similar for control and filgrastim-treated patients . CONCLUSION Taken together , the results of this first r and omized study support the role of filgrastim given as an adjunct to ABMT in accelerating neutrophil recovery , as well as in reducing treatment-related morbidity and overall duration of the treatment procedure We have tested the benefit of prophylaxis by intravenous systemic vancomycin among 59 neutropenic patients in a r and omized trial . Vancomycin was delivered on day zero of chemotherapy until the resolution of neutropenia in the prophylactic group ( vanco+ ) . Empiric antibiotic therapy ( piperacillin , ofloxacine ) was identical for all patients . The number of days with fever > 38.5 degrees C was significantly higher in the control ( vanco- ) group than in the vanco+ group ( 7.4 vs. 3.7 , p < 0.02 ) . Zero gram-positive infections occurred in the vanco+ group versus 9 in the vanco- group ( p < 0.002 ) . The mean number of days of empiric antibiotic therapy was reduced in the vanco+ group ( 11.3 vs. 16.3 , p = 0.12 ) . However , no benefit was noted between the two groups with regard to mortality or the severity of the infections . The selection of resistant microorganisms after systemic treatment with vancomycin is of potential risk . Such a prophylactic antibiotic regimen does not seem to be justified Background / Aims : There exists few pediatric data on the safety and efficacy of prophylactic antibiotics during chemotherapy-induced agranulocytosis . Methods : We prospect ively studied the incidence of infection-related fever in 38 children , aged 2 - 16 years , with acute myeloid leukemia ( AML ) over 121 chemotherapy treatment cycles . A prophylactic group ( n = 18 ) was given either vancomycin/cefepime ( 400 mg/m2 , q12 h/50 mg/kg , q12 h ) or piperacillin/tazobactam ( 110 mg/kg , q12 h ) . Control patients ( n = 20 ) received no preventive antibiotics . Results : The prophylactic group ( 59 treatment cycles ) experienced fever less frequently than the control group ( 0.4 vs. 0.9 events ; p < 0.001 ) , had a longer interval between agranulocytosis and fever ( 6.4 vs. 3.8 days ; p = 0.007 ) , had a shorter duration of hospitalization ( 21.5 vs. 28.5 days ; p < 0.001 ) , and had a lower rate of lung infection ( 38.8 vs. 80.0 % ; p < 0.001 ) . One patient taking vancomycin experienced a skin rash and 3 patients taking piperacillin/tazobactam had diarrhea ; these side effects subsided after antibiotics were discontinued . Conclusions : In children with AML , prophylactic antibiotics during the period of chemotherapy-induced agranulocytosis can effectively reduce the incidence of infectious fever and can shorten the average length of hospital stay , improving treatment success and quality of life BACKGROUND A phase 2 trial was done to study effects of varying treatment schedule of Filgrastim ( r-metHuG-CSF ) on hematologic recovery following chemotherapy . PATIENTS AND METHODS Forty-six patients with extensive small-cell carcinoma of the lung were r and omized to receive one of three Filgrastim schedules following cyclophosphamide , doxorubicin , and etoposide ( CAE ) chemotherapy for up to six cycles of treatment . Chemotherapy was delivered on days 1 - 3 of each 21-day cycle with Filgrastim initiated at 5 micrograms/kg/day subcutaneously ( SC ) beginning on day 4 , day 6 , or day 8 and continuing until post-nadir neutrophil recovery . RESULTS During the first cycle of chemotherapy , the duration of neutropenia was similar for all three schedules ; however , the pattern of absolute neutrophil count ( ANC ) recovery differed . In subsequent cycles of treatment , an improvement in the severity of neutropenia occurred in patients on the day-4 and day-6 schedules compared with the first cycle of chemotherapy . By contrast , patients on the day-8 schedule continued to experience neutropenia similar to that seen in cycle one . Patients on the day-8 schedule also experienced a greater magnitude of grade IV thrombocytopenia in later cycles of treatment . CONCLUSION Timing of Filgrastim administration post-chemotherapy has profound effects on hematologic recovery . Delay of Filgrastim until day 8 was associated with suboptimal hematologic recovery compared with administration of Filgrastim on day 4 or day 6 . Initiation of Filgrastim on day 4 or day 6 showed a similar pattern of hematologic recovery . Beginning Filgrastim on day 6 is associated with a decrease in the total dose of Filgrastim administered The management of older patients with aggressive non-Hodgkin 's lymphoma presents a challenge to the physician . Age is a poor prognostic indicator , due to reduced ability to tolerate and maintain dose-intensive chemotherapy . Generally , older patients demonstrate a lower response rate , reduced survival and increased toxicity , although the majority of large r and omised trials exclude older patients . This r and omised trial was conducted in patients 60 years or over to compare CHOP ( cyclophosphamide 750 mg m−2 , doxorubicin 50 mg m−2 , vincristine 1.4 mg m−2 , prednisolone 100 mg ) with PMitCEBO ( mitoxantrone 7 mg m−2 , cyclophosphamide 300 mg m−2 , etoposide 150 mg m−2 , vincristine 1.4 mg m−2 , bleomycin 10 mg m−2 and prednisolone 50 mg ) . Due to the myelosuppressive nature of these regimens , patients were also r and omised to the addition of G-CSF . The formal results of this trial with long-term follow-up are now reported . Data were analysed to assess efficacy and toxicity . Overall response rate was 84 % in the CHOP arm and 83 % in the PMitCEBO arm , with overall response rates of 83 % for the use of G-CSF and 84 % for no G-CSF . At median 44 months follow-up , there was no significant difference in failure-free , progression-free or overall survival between the CHOP and PMitCEBO arms . At 3 years , the actuarial failure-free survival was 44 % in CHOP recipients and 42 % in PMitCEBO recipients and the 3-year actuarial overall survival was 46 % and 45 % respectively . There was no significant difference in the failure-free , progression-free or overall survival with the addition of G-CSF Abstract A prospect i ve , r and omized , double-blind , multicenter study in cancer patients receiving myelosuppressive chemotherapy was undertaken to evaluate and compare the tolerability of sargramostim ( yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor , RhuGM-CSF ) and filgrastim ( bacteria-derived recombinant human granulocyte colony-stimulating factor , RhuG-CSF ) in the prophylaxis or treatment of chemotherapy-induced neutropenia . In all , 137 evaluable patients received sargramostim ( 300 μg ; 193 mg/m2 ) or filgrastim ( 481 mg ; 7 mg/kg ) once daily by self-administered s.c . injection , usually beginning within 48 h after completion of chemotherapy . With the exception of a slightly higher incidence of grade 1 fever ( /38.1 ° C ) with sargramostim , there were no statistically significant differences in the incidence or severity of local or systemic adverse events possibly related to the growth factors . Although the study was not design ed to evaluate efficacy directly , there also were no statistically significant differences between treatment groups in total days of growth factor therapy , days of hospitalization , or days of i.v . antibiotic therapy during the treatment period . Both sargramostim and filgrastim were comparably well tolerated when given by s.c . injection in this group of patients , and no clinical ly significant differences between the growth factors were demonstrated PURPOSE A prospect i ve r and omized trial to determine if granulocyte colony-stimulating factor ( G-CSF ) could increase the received dose-intensity ( RDI ) of weekly chemotherapy in patients with small-cell lung cancer ( SCLC ) . PATIENTS AND METHODS Forty patients with SCLC with good prognostic features ( all patients with limited disease [ LD ] , and extensive-disease [ ED ] patients with Eastern Cooperative Oncology Group [ ECOG ] 0 or 1 and plasma alkaline phosphatase levels < 1.5 times the upper limit of normal ) were r and omized to receive weekly chemotherapy with or without G-CSF . G-CSF ( 5 micrograms/kg ) was self-administered subcutaneously on days when chemotherapy was not given . Chemotherapy consisted of cisplatin 50 mg/m2 intravenously ( IV ) on day 1 and etoposide 75 mg/m2 IV on days 1 and 2 alternating weekly with ifosfamide 2 g/m2 IV ( with mesna ) and doxorubicin 25 mg/m2 on day 1 , for a total of 12 courses . Dose modifications ( dose reductions and treatment delays ) were made according to defined hematologic criteria . RESULTS Dose reductions were made at some point during treatment in 12 of 17 patients in the control arm and in 11 of 23 patients in the G-CSF arm ( P = .20 ) . The proportion of patients experiencing dose reductions due to leukopenia was significantly higher in the control arm ( nine of 17 ) compared with the G-CSF arm ( four of 23 , P < .04 ) . Cycle delays due to leukopenia were similar in both arms of the study . The RDI was 82 % of projected in the control arm ( 95 % confidence interval [ CI ] , 79 % to 84 % ) and 84 % in patients receiving G-CSF ( 95 % CI , 82 % to 87 % ) ( P value not significant ) . CONCLUSION In this r and omized trial , G-CSF significantly decreased dose reductions due to neutropenia . However , administration of G-CSF did not decrease dose reductions or treatment delays to a level that would allow an increase in received dose-intensity . Nonhematologic toxicities such as increased creatinine concentration also prevented an increase in the RDI in the G-CSF arm A r and omized , double-blind , placebo-controlled trial was conducted in eight hematologic units to determine the efficacy and safety of oral enoxacin for infection prevention in adult patients with acute nonlymphocytic leukemia . One hundred nineteen patients undergoing remission induction or consolidation chemotherapy were enrolled ; 62 of them received enoxacin ( 400 mg orally every 12 h ) . Patients received antifungal prophylaxis with oral mycostatin ( 1,000,000 U four times daily ) or clotrimazole ( 1 troche five times daily ) . Analysis was performed on an intent-to-treat basis . There was no significant difference between groups in race , age , or type and stage of leukemia , but there were more males in the placebo group ( P = 0.073 [ Fisher 's exact test ] ) . Fewer enoxacin patients had gram-negative bacteremia ( 1 versus 14 [ P < 0.001 ] ) , gram-negative infection at any site ( 2 versus 19 [ P < 0.001 ] ) , or bacterial and /or fungal infection ( 17 versus 26 [ P = 0.056 ] ) . There was no significant difference in the number of patients with gram-positive infection at any site ( 12 versus 16 ) , gram-positive bacteremia ( 9 versus 10 ) , deep fungal infection ( 6 versus 2 ) , death ( 2 versus 3 ) , other antimicrobial therapy required ( 48 versus 48 ) , therapy with amphotericin B ( 15 versus 7 [ P = 0.105 ] ) , any adverse event ( 45 versus 36 ) , or any study drug-associated adverse events ( 13 versus 6 ) . Logistic regression confirmed ( odds ratios and 95 % confidence intervals are given in parentheses ) that enoxacin reduced the risk of gram-negative infection ( 0.07 ; 0.01 to 0.30 ) , especially gram-negative bacillary bacteremia ( 0.05 ; 0.01 to 0.37 ) , without altering the risk of gram-positive bacterial ( 0.63 ; 0.26 to 1.5 ) , deep fungal ( 2.57 ; 0.47 to 13.9 ) , or Clostridium difficile ( 1.16 ; 0.3 to 4.56 ) infection . The median time to the onset of fever of more than or equal 102.8 F ( 39.3 degree C ) was 32 days for the enoxacin group versus 15 days for patients receiving placebo ( P=0.0007 [ Wilcoxon test ] ) . In patients with acute nonlymphocytic leukemia , oral enoxacin prevents gram-negative infections , delays the onset of fever , does not alter the incidence of gram-positive or proven deep fungal infections , and is well tolerated 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 The European Lung Cancer Working Party ( ELCWP ) design ed a 3-arm phase III r and omised trial to determine the role of accelerated chemotherapy in extensive-disease ( ED ) small-cell lung cancer ( SCLC ) . Eligible patients were r and omised between the 3 following arms : ( A ) St and ard chemotherapy with 6 courses of EVI ( epirubicin 60 mg m–2 , vindesine 3 mg m–2 , ifosfamide 5 g m–2 ; all drugs given on day 1 repeated every three weeks . ( B ) Accelerated chemotherapy with EVI administered every 2 weeks and GM-CSF support . ( C ) Accelerated chemotherapy with EVI and oral antibiotics ( cotrimoxazole ) . Primary endpoint was survival . 233 eligible patients were r and omised . Chemotherapy could be significantly accelerated in arm B with increased absolute dose-intensity . Best response rates , in the population of evaluable patients , were , respectively for arm A , B and C , 59 % , 76 % and 70 % . The response rate was significantly higher in arm B in comparison to arm A ( P = 0.04 ) . There was , however , no survival difference with respective median duration and 2-year rate of 286 days and 5 % for arm A , 264 days and 6 % for arm B and 264 days and 6 % for arm C. Severe thrombopenia occurred more frequently in arm B but without an increased rate of bleeding . Non-severe infections were more frequent in arm B and severe infections were less frequent in arm C. Our trial failed to demonstrate , in ED-SCLC , a survival benefit of chemotherapy acceleration by using GM-CSF support . © 2001 Cancer Research Campaign OBJECTIVE To determine the clinical and economic effects of granulocyte macrophage colony-stimulating factor ( GM-CSF ) as adjunct therapy in relapsed or refractory Hodgkin disease . DESIGN A r and omized , double-blind , phase III clinical trial . SETTING A tertiary referral center . PATIENTS Twenty-four patients ( twelve of whom were controls ) treated with high-dose chemotherapy and autologous bone marrow transplantation . MAIN RESULTS The 12 patients treated with GM-CSF , when compared with placebo recipients , had shorter periods of neutropenia ( median duration of an absolute neutrophil count of less than 1000 cells/mm3 , 16 days compared with 27 days ; P = 0.02 ) , shorter periods of platelet-transfusion dependency ( median duration , 13.5 days compared with 21 days ; P = 0.03 ) , and shorter hospitalizations ( median hospital stay , 32 days compared with 40.5 days ; P = 0.004 ) . Other clinical outcomes , such as frequency and severity of toxicities , development of pneumonia or infection , in-hospital death , and response rate were similar in the two groups . Actuarial long-term disease-free survival was 64 % for patients treated with GM-CSF and 58 % for patients who received placebo after 32 months of follow-up ( P = 0.15 ) . The group treated with GM-CSF had lower total charges after infusion of autologous marrow than the placebo group ( median in-hospital charges , $ 39,800 compared with $ 62,500 ; P = 0.005 ) because of lower post-infusion charges for room and board , antibiotic therapy , transfusions , laboratory tests , and physical therapy visits . CONCLUSIONS Administration of GM-CSF was associated with acceleration of myeloid and platelet recovery and was cost effective in the treatment of patients with relapsed Hodgkin disease who received intensive chemotherapy This prospect i ve multicenter study examined whether simultaneous administration of granulocyte colony-stimulating factor ( G-CSF ; Filgrastim ) and induction chemotherapy for adult acute lymphoblastic leukemia ( ALL ) could prevent treatment-related neutropenia , infections , and result ing treatment delays . Seventy-six patients were r and omly assigned to receive either G-CSF ( n = 37 ) or no growth factor ( n = 39 ) in conjunction with a uniform chemotherapy consisting of cyclophosphamide , cytarabine , mercaptopurine , intrathecal methotrexate , and cranial irradiation . The median duration of neutropenia ( absolute neutrophil count < 1 x 10(9)/L ) during chemotherapy was 8 days in patients receiving C-CSF , compared with 12.5 days in the control group ( P < .002 ) . A similar reduction from 11.5 to 7 days was observed in patients with T-ALL receiving additional mediastinal irradiation ( P = .13 ) . Infections occurred in 43 % and 56 % of patients in the G-CSF and control arm , respectively ( P = .25 ) ; the incidence of nonviral infections was reduced by 50 % , from 32 episodes in the control arm to 16 episodes in the G-CSF arm . Prolonged interruptions of chemotherapy administration were less frequent , with delays of 2 weeks or more occurring in only 24 % of patients receiving G-CSF as opposed to 46 % in the control arm ( P = .01 ) . Accordingly , chemotherapy was completed significantly earlier with the use of G-CSF ( 39 v 44 days , P = .008 ) . With a median follow-up of 20 months , the probability of disease-free survival was 0.45 in the G-CSF group and 0.43 in the control group ( P = .34 ) . In conclusion , adult ALL patients appear to benefit by the simultaneous administration of G-CSF with induction chemotherapy because of a significant reduction in the duration of neutropenia , a trend to fewer infections , and a more rapid completion of chemotherapy Because of the recommendation to avoid the concomitant administration of growth factors and chemotherapy , there is only limited information on colony-stimulating factor ( CSF ) therapy in acute lymphoblastic leukemia ( ALL ) induction protocol s , in which cytotoxic drugs are administered in divided doses over a prolonged period of time , thus requiring a simultaneous administration of growth factors and chemotherapy . We conducted a prospect i ve , r and omized , controlled study to determine the safety and efficacy of granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) as an adjunct to phase I of induction chemotherapy for adult ALL . Patients ( n = 53 ) were r and omized to receive no growth factor or G-CSF ( 5 microg/kg/d subcutaneously ) starting on day 2 of chemotherapy consisting of daunorubicin ( 45 mg/m2 ) and vincristine ( 1.5 mg/m2 ) on days 1 , 8 , 15 , and 22 ; L-asparaginase ( 2500 U/m2 ) on days 1 through 14 ; and prednisone ( 60 mg/m2 ) on days 1 through 28 . A total of 25 patients in the G-CSF group and 26 patients in the control arm fulfilled the inclusion criteria of the study . G-CSF markedly ameliorated neutropenia because the median proportion of days with neutropenia less than 1,000/microL was 29 % in the G-CSF group as compared with 84 % in the control arm ( P < .00005 ) . The median time to reach absolute neutrophil counts ( ANC ) > or = 1,000/microL was 16 days in G-CSF patients and 26 days in controls ( P < .001 ) . More importantly , G-CSF significantly reduced the incidence of febrile neutropenia ( 12 % v 42 % in controls , P < .05 ) and documented infections ( 40 % v 77 % , P < .05 ) . No significant differences were found with regard to requirements for red blood cell transfusions and platelet concentrates . A total of 24 of 25 ( 96 % ) patients in the G-CSF group and 20 of 25 ( 80 % ) evaluable control patients had complete remission after phase I of induction therapy . We conclude that G-CSF can be safely administered as an adjunct to induction therapy of ALL and is clinical ly beneficial by ameliorating neutropenia and reducing infectious complications PURPOSE As bone marrow toxicity is the major limitation of the optimal administration of chemotherapy , we investigated whether recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) could prevent myelotoxicity or accelerate hematopoietic recovery after mechlorethamine , vincristine , procarbazine , and prednisone ( MOPP ) chemotherapy . PATIENTS AND METHODS Twenty-four previously untreated patients with Hodgkin 's disease were included in a phase I/II study in which st and ard MOPP chemotherapy was followed by 5 days of GM-CSF at every other cycle . Patients were entered sequentially to receive one of four dosc levels ( 2 , 4 , 8 , and 16 micrograms/kg of glycoprotein ; 1.4 , 2.8 , 5.5 , and 11.0 micrograms/kg of protein ) and were r and omly allocated to either 24-hour continuous intravenous ( IV ) infusion or twice daily subcutaneous ( SC ) injection of rhGM-CSF . RESULTS WBC counts ( mainly neutrophils , eosinophils , and monocytes ) were significantly higher in cycles with rhGM-CSF than in cycles with MOPP alone . The total number of days of leukopenia ( WBC count less than or equal to 2.0 x 10(9)/L ) and neutropenia ( absolute neutrophil count [ ANC ] less than or equal to 1.0 x 10(9)/L ) was reduced in cycles with rhGM-CSF from 6.3 to 0.8 days and from 5.4 to 1.0 days , respectively . All dose levels of rhGM-CSF were effective in increasing the ANC , but only at the dose levels of 8 and 16 micrograms/kg did this significantly affect the scheduling of chemotherapy . Mild and reversible adverse reactions included low- grade fever , chest/bone pain , myalgias , erythemia , headache , fatigue , and periorbital edema . CONCLUSIONS rhGM-CSF can be administered safely to patients with Hodgkin 's disease and results in improved hematologic recovery after MOPP . Full-dose chemotherapy can be administered on time , result ing in an increase in the overall tolerated dose of myelosuppressive drugs when compared with historical controls . SC administration proved to be at least as effective as continuous IV infusion and should be preferred A r and omised study was conducted in 62 patients with advanced breast cancer to assess whether granulocyte-macrophage colony-stimulating factor ( GM-CSF ) would yield an increase in the dose intensity of a st and ard-dose CEF regimen through an acceleration of chemotherapy administration . Patients received CEF ( cyclophosphamide 600 mg m-2 , epidoxorubicin 60 mg m-2 and fluorouracil 600 mg m-2 ) i.v . on day 1 or the same chemotherapy , plus GM-CSF 10 micrograms kg-1 s.c . starting from day 4 , repeated as soon as haematopoietic recovery from nadir occurred . Patients in the CEF + GM-CSF group received chemotherapy at a median interval of 16 days compared with 20 days in the control group . This led to a significant increase ( P = 0.02 ) in the dose intensity actually administered in the third , fourth and sixth cycles : + 28 % , + 25 % , + 20 % respectively . Non-haematological toxicity was mild . GM-CSF had to be reduced or suspended in 50 % of patients because of toxicity . Haematological toxicity , mainly cumulative anaemia and thrombocytopenia , was manageable . An increase in response rate for patients with measurable disease , of borderline statistical significance ( P = 0.088 , P for trend = 0.018 ) , from 42 % in the CEF group to 69 % in the CEF + GM-CSF group , was observed . This r and omised trial indicates that GM-CSF is useful for chemotherapy acceleration . Accelerated CEF + GM-CSF is a moderately dose-intensive regimen that can be administered in an outpatient clinic and is associated with a high objective response 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 a prospect i ve r and omized trial , 40 stage IV breast cancer patients undergoing intermediate high-dose chemotherapy ( cyclophosphamide , 5-fluorouracil plus epirubicin or methotrexate ) , received either recombinant human G-CSF ( rhG-CSF , group I ) or ciprofloxacin and amphotericin B ( CAB , group II ) for prevention of febrile leucopenia ( FL ) . In group I , seven of 18 patients developed FL ( after 10/108 courses ) ; in group II , seven of 22 patients ( 7/98 courses ) ( P = NS ) . Median hospitalization duration and costs were not different . RhG-CSF was 6.6 times more expensive per course than CAB . In conclusion , prophylactic CAB has similar efficacy to rhG-CSF in this setting , and is more cost-effective The aim of this study was to determine the usefulness of recombinant human granulocyte colony stimulating factor ( r-metHuG-CSF ) following conventional chemotherapy for small cell lung cancer . 130 previously untreated patients were r and omised to receive either r-metHuG-CSF ( 230 micrograms/m2 ) or placebo on days 4 - 17 following CDE ( cyclophosphamide , doxorubicin and etoposide ) chemotherapy . Over all cycles , 53 % of 64 patients on placebo and only 26 % of 65 patients on r-metHuG-CSF had at least one experience of neutropenia with fever defined as a neutrophil count less than 1.0 x 10(9)/l and a temperature > or = 38.2 degrees C ( P < 0.002 ) . It result ed in a reduction in the requirement for parenteral antibiotics from 58 % in placebo patients compared with 37 % in the r-metHuG-CSF group ( P < 0.02 ) , and a significant reduction in the incidence of infection-related hospitalisation . Chemotherapy doses were reduced by 15 % or more at least once in 61 % of the placebo group compared with 29 % in the r-metHuG-CSF group ( P < 0.001 ) . 47 % of the patients treated with placebo and 29 % of the patients treated with r-metHuG-CSF experienced at least one cycle with a delay of 2 days or more in the administration of chemotherapy ( P < 0.04 ) . r-metHuG-CSF was well tolerated . There were no significant differences between the two groups in terms of response or survival Shortening duration of chemotherapy-induced neutropenia may reduce risk of infection and aid subsequent chemotherapy delivery . Cycle 1 neutrophil recovery was evaluated in 59 elderly women with breast cancer receiving adjuvant FEC100 ( 5-fluorouracil 500 mg/m(2 ) , epirubicin 100mg/m(2 ) and cyclophosphamide 500 mg/m(2 ) ) and r and omized to pegfilgrastim primary prophylaxis ( PP ) from cycle 1 , or secondary prophylaxis ( SP , i.e. , subsequent to a neutropenic event [ no G-CSF in cycle 1 ] ) . In cycle 1 , grade 4 neutropenia occurred in 77 % ( PP ; N=30 ) and 72 % ( SP ; N=29 ) . Duration of grade 3 - 4 neutropenia was shorter with pegfilgrastim than without . Mean absolute neutrophil count ( ANC ) recovered above 1.0 x 10(9)/L by day 9 ( pegfilgrastim ) versus days 16 - 18 ( without ) . At last observation ( > or = day 14+/-2 ) , no PP patient had ANC < 1.0 x 10(9)/L versus approximately 25 % of those receiving no pegfilgrastim . In conclusion , cycle 1 pegfilgrastim improved recovery from severe neutropenia in elderly breast cancer patients receiving adjuvant FEC100 PURPOSE Early breast cancer is commonly treated with anthracyclines and taxanes . However , combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor ( G-CSF ) support . The highest incidence of febrile neutropenia ( FN ) and largest benefit of G-CSF during the first cycles of chemotherapy lead to questions about the effectiveness of continued use of G-CSF throughout later cycles of chemotherapy . PATIENTS AND METHODS In a multicenter study , patients with breast cancer who were considered fit enough to receive 3-weekly polychemotherapy , but also had > 20 % risk for FN , were r and omly assigned to primary G-CSF prophylaxis during the first two chemotherapy cycles only ( experimental arm ) or to primary G-CSF prophylaxis throughout all chemotherapy cycles ( st and ard arm ) . The noninferiority hypothesis was that the incidence of FN would be maximally 7.5 % higher in the experimental compared with the st and ard arm . RESULTS After inclusion of 167 eligible patients , the independent data monitoring committee advised premature study closure . Of 84 patients r and omly assigned to G-CSF throughout all chemotherapy cycles , eight ( 10 % ) experienced an episode of FN . In contrast , of 83 patients r and omly assigned to G-CSF during the first two cycles only , 30 ( 36 % ) had an FN episode ( 95 % CI , 0.13 to 0.54 ) , with a peak incidence of 24 % in the third cycle ( ie , first cycle without G-CSF prophylaxis ) . CONCLUSION In patients with early breast cancer at high risk for FN , continued use of primary G-CSF prophylaxis during all chemotherapy cycles is of clinical relevance and thus can not be ab and oned The effect of granulocyte colony-stimulating factor ( G-CSF ) on neutropenia , infection , and cytotoxic chemotherapy administration was studied in a r and omized trial in patients receiving intensive weekly chemotherapy for non-Hodgkin 's lymphoma ( NHL ) . Eighty patients ( aged 16 to 71 years ) with high- grade NHL ( Kiel ) of any stage were r and omized to receive VAPEC-B chemotherapy alone ( 39 patients ) or with G-CSF administered as a daily subcutaneous dose of 230 micrograms/m2 ( 41 patients ) . Prophylactic ketoconazole and cotrimoxazole were administered to all patients throughout treatment . The protocol specified identical dose modification and antibiotic treatment criteria bor both groups . Neutropenia ( absolute neutrophil count [ ANC ] less than 1.0 x 10(9)/L ) occurred in 15 of 41 ( 37 % ) of the G-CSF-treated patients and in 33 of 39 ( 85 % ) of the controls , giving a relative risk for control patients of 2.31 ( 95 % confidence interval [ CI ] , [ 1.51 , 3.54 ] ; P = .00001 ) . Fever ( greater than or equal to 37.5 degrees C ) with neutropenia ( ANC less than 1.0 x 10(9)/L ) occurred in 9 of 41 ( 22 % ) of the G-CSF group and in 17 of 39 ( 44 % ) of the controls ( relative risk for control , 2.26 ; 95 % CI [ 1.01 , 5.06 ] ; P = .04 ) . There were fewer treatment delays , with shorter duration ( P = .01 ) in patients receiving G-CSF . Chemotherapy doses were reduced in 4 of 41 ( 10 % ) of the G-CSF patients and 13 of 39 ( 33 % ) of the controls ( P = .01 ) . The dose intensity of cytotoxic chemotherapy was significantly increased in patients receiving G-CSF ( median of 95 % in G-CSF group compared with 83 % in control patients ) . Three vascular deaths occurred in the G-CSF group . Delays in the control group most commonly result ed from neutropenia ( 19 patients , compared with 2 patients in the G-CSF-treated group , P = .000007 ) . Severe mucositis was the major dose-limiting toxicity in G-CSF-treated patients , but did not occur more frequently than in controls ( 15 patients in each group ) . Overall , patients r and omized to receive G-CSF achieved a greater dose intensity than control patients , but this did not result in significant differences in drug toxicity ( other than neutropenia ) , intravenous antibiotic usage , or hospitalization between the two groups This is a double‐blind r and omized placebo‐controlled trial to evaluate the efficacy and safety of granulocyte‐macrophage colony‐stimulating‐factor ( GM‐CSF ) after dose‐intensive cyclophosphamide , etoposide , and cisplatin ( DICEP ) . Fifty‐six patients with lymphoma or breast carcinoma were r and omized to receive GM‐CSF 250 μg/m2 or placebo subcutaneously ( SC ) every 12 hr after each course of DICEP until recovery of absolute neutrophil count ( ANC ) of 1.5 × 109/L. Each patient was to receive three courses of DICEP . There were 28 patients in each group . The median duration of ANC below 0.5 × 109/L was 10 versus 12 days for Course 1 ( P = 0.010 ) , 10 versus 12 days for Courses 2 ( P = 0.248 ) , and 16.5 versus 15 days for Course 3 ( P = 0.126 ) ; platelet counts below 20 × 109/L was 4 versus 4 days for Course 1 ( P = 0.586 ) , 8.5 versus 7 days for Course 2 ( P = 0.013 ) , and 23.5 versus 10.5 days for Course 3 ( P = 0.104 ) ; hospitalization for patients readmitted with cytopenic fever were 4 versus 8 days for Course 1 ( P = 0.035 ) ; 7 versus 6 days for Course 2 ( P = 0.692 ) ; and 8 versus 12 days for Course 3 ( P = 0.884 ) in the GM‐CSF and placebo group , respectively . GM‐CSF significantly shortens the duration of neutropenia and readmission only during the first course of DICEP . There was a delay in platelet recovery and an increase in transfusion requirement during subsequent courses in the GM‐CSF group . The result caution s the routine use of lineage specific hematopoietic growth factors in supporting repeated cycles of dose‐intensive chemotherapy . © 1996 Wiley‐Liss , Background Febrile neutropenia ( FN ) remains a major dose-limiting complication among patients treated with chemotherapy . Haematopoietic colony stimulating factors ( G-CSF and GM-CSF ) made possible a significant improvement in the management of FN , both in the therapeutic and in the prophylactic approach . The use of antibiotic prophylaxis also permits a definite reduction of severe infections during neutropenia . Nevertheless , the possible role of these two interventions for secondary prevention of FN is still unclear . Patients and methods We conducted a prospect i ve r and omised trial by comparing the efficacy of granulocyte-colony stimulating factor ( G-CSF ) and the association of G-CSF with oral antibiotics in the secondary prevention of FN . We included in our study those patients who , after an episode of FN , continued to be treated with the same chemotherapy without reduction of dose intensity . They were r and omised into two groups : the first received G-CSF ( group G ; filgrastim , 5 µg/kg day ) , and the second was treated with an association of G-CSF and amoxicillin/clavulanate plus ciprofloxacin ( group G/ACC ) . Results Forty-eight patients were r and omised ( group G : n=23 and group G/ACC : n=25 ) . There was no recurrence of FN among the patients receiving G-CSF and only one episode in the combined therapy group ( p=1 ) . With regard to the side effects , there was no significant difference in the two groups . Conclusion The use of G-CSF for the secondary prevention of FN is extremely effective and allows the maintenance of chemotherapy dose intensity . Our study showed that the addition of antibiotics does not seem to be required Children with acute myelogenous leukemia ( AML ) have a high risk of infectious complications that might be reduced by prophylactic granulocyte colony-stimulating factor ( G-CSF ) . However , G-CSF could induce AML blast proliferation . The prospect i ve r and omized trial AML-BFM 98 investigated the impact of G-CSF on hematopoetic recovery and infectious complications ( primary endpoints ) and on outcome ( secondary endpoint ) in children ( aged 0 - 18 years ) with de novo AML . Patients with more than 5 % blasts in day-15 bone marrow or with FAB M3 were not included . Between 1998 and 2003 , 161 children with AML were r and omized to receive G-CSF after inductions 1 and 2 , whereas 156 patients were assigned to the control group . Time of neutropenia after inductions 1 and 2 was significantly shorter in the G-CSF group ( 23 vs 18 days and 16 vs 11 days ; P=.02 and = .001 , respectively ) . G-CSF did not decrease the incidence of febrile neutropenia ( 72 and 36 patients vs 78 and 37 patients , respectively ) , microbiologically documented infections ( 27 and 25 patients vs 36 and 19 patients , respectively ) and infection-associated mortality ( 5 vs 2 patients ) . Both groups had similar 5-year event-free survival ( EFS ; 59%+/-4 % vs 58%+/-4 % ) . Since G-CSF does not influence the risk of infectious complications or outcome in children undergoing therapy for AML , one can not advocate the routine use of G-CSF in this patient group PURPOSE To determine the effects of sargramostim ( recombinant human granulocyte-macrophage colony-stimulating factor [ rhu GM-CSF ] ) on the incidence , duration , and complications of myelosuppression after moderate-dose fluorouracil , doxorubicin , cyclophosphamide ( FAC ) adjuvant chemotherapy in patients with node-positive breast cancer . PATIENTS AND METHODS In this r and omized , double-blind , placebo-controlled study , 142 women with stage II and III breast cancer were to receive four 21-day cycles of chemotherapy that consisted of fluorouracil 600 mg/ m2 intravenously ( IV ) , doxorubicin 60 mg/m2 IV , and cyclophosphamide 750 mg/m2 IV on day 1 , followed by placebo or GM-CSF 250 micrograms/m2/d daily subcutaneously ( SC ) on days 3 through 15 . All patients received prophylactic ciprofloxacin by mouth when the absolute neutrophil count ( ANC ) was less than 1,000/microL. RESULTS Eighty-six percent of GM-CSF patients ( n = 62 ) and 96 % of placebo patients ( n = 69 ) completed four assessable cycles of treatment on study . Overall , the median duration of severe neutropenia ( ANC < 500/microL ) was 2.8 days with GM-CSF and 6.8 days with placebo ( P < .001 ) ; the duration of ANC less than 1,000/microL was 6.0 versus 9.1 days , respectively ( P < .001 ) . Hospitalizations for febrile neutropenia were uncommon in either group : GM-CSF , six ; placebo , eight . The only other difference in hematologic toxicity was grade 3/4 thrombocytopenia observed with greater frequency in GM-CSF patients than placebo patients in cycles 3 and 4 . GM-CSF increased mean the FAC dose-intensity among patients who completed two or more cycles ( P < .001 ) . GM-CSF was generally well tolerated and associated with more injection-site reactions , but less mucositis than placebo . There were no deaths on study . CONCLUSION GM-CSF significantly enhanced ANC recovery after FAC chemotherapy ; it decreased the incidence and duration of associated neutropenia and moderately increased the dose-intensity of adjuvant chemotherapy . Whether these effects will ultimately translate into improved long-term outcome remains to be determined PURPOSE To compare the efficacy and safety of ciprofloxacin ( CIP ) and trimethoprim/sulfamethoxazole ( TMS ) for the prevention of bacterial infections in patients who received bone marrow transplantation ( BMT ) for the treatment of solid and hematopoietic neoplasms . PATIENTS AND METHODS Adult in patients about to undergo BMT for lymphoma , leukemia , or solid tumors were enrolled onto a prospect i ve , r and omized , double-blinded , controlled trial that compared CIP ( 750 mg orally twice per day ) with TMS ( 160 mg trimethoprim and 800 mg sulfamethoxazole orally twice per day ) . Subjects were stratified before r and omization according to tumor and BMT type . Prophylaxis was begun within 96 hours of initiation of the BMT preparative regimen and continued until the onset of fever , signs or symptoms of infection , serious adverse effects , or recovery of the absolute granulocyte count ( AGC ) to > or = to 400/microL. RESULTS Seventy-five CIP recipients and 71 TMS recipients were assessable for efficacy . No difference was noted between the two groups in occurrence of fever during neutropenia , time to onset of first fever , or overall infection rates . Ten bacteremias occurred in CIP recipients versus six in TMS recipients ( P = .43 ) . Ten episodes of Clostridium difficile enterocolitis occurred in TMS recipients versus no episodes in CIP recipients ( P = .001 ) . Four infections caused by gram-negative bacilli , including one bacteremia , occurred in TMS recipients versus none in CIP recipients ( P = .06 ) . No differences were noted in the incidence of rash or organ toxicity . TMS recipients had longer duration s of granulocytopenia at AGC levels < or = to 500/microL and < or = to 100/microL than did CIP recipients ( P = .08 for both comparisons ) . Mean peak and trough serum levels of CIP decreased significantly between weeks 1 and 2 of prophylaxis . CONCLUSION CIP and TMS were equally safe and effective in the prevention of bacterial infections in BMT patients when the overall infection rate was used as the principal end point . TMS prophylaxis was associated with a higher incidence of C difficile enterocolitis and infections caused by gram-negative bacilli , as well as a trend toward prolongation of granulocytopenia The effect of a combination regimen using norfloxacin ( NFLX ) and amphotericin B ( AMPH-B ) for prevention of infections in patients with acute leukemia being treated by remission-induction chemotherapy in a r and omized , controlled trial was studied . One hundred and six consecutive , evaluable patients were r and omly assigned to receive orally 200 mg of norfloxacin two or four times daily and 200 mg of amphotericin B four times daily , or amphotericin B only . A smaller percentage of patients with bacteriologically-documented infections was observed in the study group compared with the control group ( 34.6 % vs 56.9 % ; P < 0.05 ) . The mean number of days that the patients received empirical antibiotic therapy was shorter in the study group ( 23 days vs 30 days ; P < 0.05 ) . The percentage of patients with a gram-negative bacterial infection ( 9.6 % vs 27.5 % ; P < 0.05 ) or a fungal infection ( 17.3 % vs 37.3 % ; P < 0.05 ) was decreased in the study group . This new combination antimicrobial regimen is safe and effective for prevention of gram-negative bacterial as well as fungal infections in patients with acute leukemia being treated with cytotoxic remission-induction chemotherapy Abstract : The present trial was design ed to test the effects of G‐CSF on the duration of the second phase of induction chemotherapy in children with newly diagnosed acute lymphoblastic leukemia ( ALL ) . A total of 32 patients were assigned r and omly to a group that received ( 14 patients ; group A ) or a group that did not receive ( 18 patients ; group B ) G‐CSF ( 10 g/kg/day subcutaneously and daily ) throughout of the second phase of induction therapy . One of 14 ( 7.1 % ) patients in group A and 2 of 18 ( 11.1 % ) patients in group B completed the course of chemotherapy within the planned time . The median length of this phase was 37 days ( range , 29 to 65 ; mean , 40 ; SD , 8.6 ) for patients in group A and 36 days ( range , from 29 to 55 ; mean , 38 ; SD , 7.4 ) for those in group B , and the difference was not statistically significant . The number of days during which patients had granulocyte counts of less than 2 × 109/l , the number of febrile episodes of unknown origin , the number of bacterial and fungal infections and the number of days of hospitalization did not differ in a statistically significant manner between the two groups . Our data suggest that G‐CSF supportive therapy may be unnecessary in children with neutropenia of short duration , for whom the risk of infection is low We studied the impact of CHOP chemotherapy on the quality of life ( QoL ) of elderly patients with aggressive non-Hodgkin 's lymphoma ( NHL ) . 132 patients aged 65 or older , who participated in a r and omized , multicenter trial , completed QoL question naires ( EuroQol-5D , EORTC QLQ-C30 and MFI-20 ) on 8 predefined time-points before , during and following treatment . At baseline , QoL was significantly better on almost all dimensions in patients with a lower compared to patients with a higher age-adjusted International Prognostic Index ( aaPI ) . During treatment , physical and role functioning and global QoL deteriorated and fatigue increased in the lower aaPI group , whereas QoL of the higher aaPI group remained stable . During follow-up , the QoL was significantly better for patients in complete response ( CR ) or partial remission ( PR ) than for patients with progression/relapse . Soon after completion of therapy , the QoL of the lower aaPI group returned to pretreatment levels or better , while patients with higher aaPI showed a significant improvement in QoL compared to baseline levels . The effect of CHOP on the quality of life of elderly patients could be used in counseling this group of patients This r and omized phase 2 study explored the feasibility of delivering four to six cycles of the dose-intensified regimen FEC-100 ( 5-fluorouracil , epirubicin , and cyclophosphamide ) to elderly patients with stage II-III breast cancer , using pegfilgrastim for neutrophil support . Sixty patients aged 65 - 77 years received single 6 mg doses of pegfilgrastim on day 2 of FEC-100 , either as primary prophylaxis ( all cycles : PP ) , or as secondary prophylaxis ( all cycles following a neutropenic event : SP ) . Neutropenic events ( a composite endpoint that included grade 3 neutropenia+fever , grade 4 neutropenia , infectious complication requiring systemic anti-infectives and chemotherapy dose delay/reduction ) occurred in 24/30 ( 80 % ) of the PP and 21/29 ( 72 % ) of the SP group in the first cycle . Most patients received all chemotherapy cycles at full dose on schedule ( 26/30 [ 87 % ] PP ; 20/29 [ 69 % ] SP ) . These data indicate that delivery of FEC-100 is feasible with pegfilgrastim support in elderly breast cancer patients BACKGROUND Adding irinotecan and /or oxaliplatin to every-2-week 5-fluorouracil (5-FU)/leucovorin ( LV ) prolongs survival in patients with colorectal cancer ( CRC ) but increases neutropenia frequency . Pegfilgrastim is indicated to decrease infection as manifested by febrile neutropenia ( FN ) in patients receiving chemotherapy at > 14-day intervals . This r and omized , placebo-controlled phase II study examined pegfilgrastim efficacy and safety in patients with CRC receiving every-2-week chemotherapy . PATIENTS AND METHODS Patients with CRC were r and omized 1:1 to pegfilgrastim 6 mg or placebo administered per-cycle on day 4 . R and omization was stratified by chemotherapy regimen ( patients received every-2-week FOLFOX4 [ 5-FU/LV/oxaliplatin ] , FOLFIRI [ 5-FU/LV/irinotecan ] , or FOIL [ 5-FU/LV/oxaliplatin/irinotecan ] at physician discretion ) . The primary endpoint was incidence of grade 3/4 neutropenia . Secondary endpoints included incidence of grade 3/4 FN and adverse events . After 4 cycles of study treatment , progression-free survival ( PFS ) and overall survival ( OS ) were followed for < or= 2 years in long-term follow-up . RESULTS Of 241 eligible patients analyzed , 118 were in the placebo and 123 in the pegfilgrastim group . In the treatment period , the odds ratio for grade 3/4 neutropenia for pegfilgrastim versus placebo was 0.19 ( 95 % CI , 0.10 - 0.37 ; P < .001 ) ; grade 3/4 FN incidence was also significantly lower in pegfilgrastim-treated patients ( 2 % ) compared with placebo-treated patients ( 8 % ; P = .04 ) . Pegfilgrastim was well tolerated , with leukocyte counts remaining stable during cycles 2 - 4 . In long-term follow-up , both treatment groups had similar PFS and OS . CONCLUSION Pegfilgrastim was well tolerated in patients with CRC receiving every-2-week chemotherapy and significantly reduced neutropenia and FN compared with placebo , though FN was uncommon in both treatment groups . Results suggest that pegfilgrastim administration is feasible in CRC patients receiving every-2-week chemotherapy This study evaluated the effect of glycosylated recombinant human granulocyte colony-stimulating factor ( rHuG-CSF ; lenograstim ) on neutrophil granulocyte counts and on cells of other haematopoietic lineages in 66 patients with solid cancer or lymphoma who received myelosuppressive chemotherapy . Beginning 1 day after completion of chemotherapy , patients received lenograstim ( at dosages of 0.5 , 2 , 5 or 10 micrograms/kg ) or vehicle subcutaneously once daily for 14 consecutive days . Compared with vehicle , lenograstim significantly accelerated neutrophil recovery after chemotherapy in a dose-dependent manner . Mean neutrophil counts recovered to > 1.0 x 10(9 ) cells/l by day 13 in the vehicle group compared with days 11 , 10 , 8 and 7 in the 0.5 , 2 , 5 and 10 micrograms/kg lenograstim groups , respectively . Doses of 0.5 and 2 micrograms/kg of lenograstim had a significant effect on the duration of neutropenia ( < 1.0 x 10(9 ) cells/l ) , the area under the absolute neutrophil count ( ANC ) curve and the time to ANC nadir . The dose of 5 micrograms/kg additionally decreased the total area of neutropenia and gave the narrowest range of values for all neutrophil parameters , while the 10 micrograms/kg dose brought no added benefit . A dose-response effect of lenograstim on time to neutrophil recovery was observed both for patients who received chemotherapy on a single day ( n = 35 ) and for those who received chemotherapy over several days ( n = 29 ) . Based on these findings , a dose of 5 micrograms/kg/day was chosen for further trials The rapid recovery of hematopoiesis after allogeneic blood stem cell transplantation has been attributed to the quality and quantity of hematopoietic progenitors in the blood stem cell grafts from filgrastim-stimulated donors . To determine whether further stimulation with filgrastim after transplantation would affect hematopoietic recovery , a prospect i ve , r and omized , controlled study was performed . Forty-two adult recipients of allogeneic blood stem cells from human leukocyte antigen-matched related donors were r and omized to receive 10 microg/kg per day filgrastim subcutaneously from day 1 through neutrophil recovery or no growth factor support after transplantation . There was no significant difference between the 2 groups in the number of CD34(+ ) cells infused ( median , 4.8 vs 4.3 x 10(6)/kg ) . Graft-versus-host ( GVHD ) disease prophylaxis consisted of tacrolimus and steroids for 9 patients and tacrolimus and minimethotrexate for 33 patients . The group receiving filgrastim had a shorter time to neutrophil levels greater than 0.5 x 10(9)/L ( day 12 vs day 15 , P = .002 ) and to neutrophil levels greater than 1.0 x 10(9)/L ( day 12 vs day 16 , P = .01 ) . The filgrastim group also had a trend for earlier discharge ( day 16 vs 20 , P = .05 ) . There was no significant difference between the groups in time to platelet recovery , number of transfusions , regimen-related toxicity , infection , incidence of GVHD , relapse , survival , or hospital charges . It can be concluded that the administration of filgrastim after allogeneic blood stem cell transplantation shortens the time to neutrophil recovery . ( Blood . 2001;97:3405 - 3410 PURPOSE To evaluate the clinical value of growth factors ( GFs ) with peripheral-blood stem cells ( PBSC ) collected following mobilization with GFs , we r and omized patients to receive or not to receive GFs following transplant . PATIENTS AND METHODS Thirty-seven patients were apheresed after receiving the combination of granulocyte colony-stimulating factor ( G-CSF ) with granulocyte-macrophage colony-stimulating factor ( GM-CSF ) at doses of 10 micrograms/kg/d and 5 micrograms/kg/d , respectively , for 6 days before apheresis and during a median of 4 days of collection s. One day after the infusion of autologous marrow and PBSC , patients were r and omly assigned to receive no GFs or a combination of G-CSF ( 7.5 micrograms/kg/d ) and GM-CSF ( 2.5 micrograms/kg/d ) , both as a 2-hour intravenous ( i.v . ) infusion twice per day until the neutrophil count was greater than 1,500/microL. RESULTS The median days to recovery to an absolute neutrophil count ( ANC ) of 100/microL ( 9 v 11.5 , P = .0005 ) , 500/microL ( 10 v 16 , P = .0004 ) , or 1,000/microL ( 12 v 21 , P = .0008 ) was shortened with the use of GFs , post-PBSC infusion . In addition , the duration of hospitalization was shorter ( 19 v 21 days , P = .0112 ) in the arm receiving GFs post-PBSC infusion . There was no significant difference between the two study arms in the duration of fever , documented septic episodes , or RBC or platelet transfusion requirements . CONCLUSION Despite faster neutrophil recovery and shortened duration of hospitalization with GFs administered after PBSC transplantation , the measured clinical variables of febrile days , septic episodes , and transfusion requirements were similar between the study arms . The use of GFs post-PBSC transfusion is associated with a modest clinical benefit 59 patients who had earlier developed an infection following antineoplastic chemotherapy were r and omised to receive either granulocyte colony-stimulating factor ( G-CSF ) alone or G-CSF+quinolone as prophylaxis during subsequent identical chemotherapy courses . 30 patients received 48 courses of G+CSF , while 29 patients received 44 courses of G-CSF+ofloxacin or ciprofloxacin . The overall infection rate was 23 % . Patients with WHO grade IV leukopenia at the onset of prophylactic treatment developed infection in 61 % of cases when on G-CSF , but only in 22 % when on G-CSF+quinolone ( P = 0.002 ) . Patients with initial leukopenia of grade WHO III-I had only a 11 % infection rate showing no significant difference between the treatment groups . The median duration of leukopenia < 1 x 10(9)/l was 4 days for patients receiving G-CSF alone and 3.5 days for those receiving additional quinolone . Patients developing infection had grade IV leukopenia for a median of 5 days . Both prophylactic treatments were well tolerated . We conclude that when prophylactic G-CSF is initiated at WHO grade IV leukopenia , addition of an oral quinolone reduces the risk of infection PURPOSE To determine whether granulocyte colony-stimulating factor ( G-CSF ; lenograstim ) decreases the incidence of febrile neutropenia after induction courses in treatment of childhood non-Hodgkin 's lymphoma ( NHL ) . PATIENTS AND METHODS Patients were r and omized to receive ( G-CSF+ ) or not receive ( G-CSF- ) prophylactic G-CSF , 5 microg/kg/d , from day 7 until an absolute neutrophil count > or = 500/microL was sustained over 48 hours , after two consecutive induction courses of cyclophosphamide 1.5 or 3 g/m(2 ) , vincristine 2 mg/m(2 ) , prednisone 60 mg/m(2)/d x 5 , doxorubicin 60 mg/m(2 ) , high-dose methotrexate 3 or 8 g/m(2 ) , and intrathecal injections ( COPAD[M ] ) on protocol s LMB89 , LMT89 , and HM91 of the French Society of Pediatric Oncology . RESULTS One hundred forty-eight patients were assessable , 75 G-CSF+ and 73 G-CSF- . Although duration of neutropenia less than 500/microL was 3 days shorter in G-CSF+ patients ( P = 10(-4 ) ) , incidence of febrile neutropenia ( 89 % v. 93 % in the first course , 88 % v. 88 % in the second course ) , duration s of hospitalization and antimicrobial therapy , percentages of infections , mucositis , and transfusions were not significantly different . Although the percentage of G-CSF+ patients commencing the following course on day 21 was significantly higher ( 84 % v 68 % after the first and 57 % v. 38 % after the second course ; P < .05 ) , the median delay between the two courses was only 1 day less in G-CSF+ patients ( median delay after first COPAD(M ) , 19 v. 20 days , P = .01 ; after second , 21 v. 22 days , P = not significant ) . Remission and survival rates were similar in both arms . CONCLUSION This study demonstrates that G-CSF did not decrease treatment-related morbidity , nor increase the dose-intensity in children undergoing COPAD(M ) induction chemotherapy for NHL Overall chemotherapeutic treatment results in pediatric acute lymphoblastic leukemia ( ALL ) are good , with event-free survival ( EFS ) rates over 70 % . However , for a subset of patients characterized by high-risk ( HR ) features the outcome is less favorable , with EFS rates below 50 % . Intensification of chemotherapy may improve the outcome for those patients , but increased toxicity , particularly myelosuppression , limits the escalation of dose intensity . Recombinant methionyl human granulocyte colony-stimulating factor ( r-metHuG-CSF ) is known to reduce myelosuppression after cancer chemotherapy in adults . The objective of this study was to examine the effect of r-metHuG-CSF on myelosuppression in HR pediatric ALL patients and on the overall response rate to chemotherapy . Patients with HR pediatric ALL were r and omized to receive nine alternating cycles of chemotherapy according to the German ALL-Berlin-Frankfurt-Münster 90 protocol either alone or followed by r-metHuG-CSF administered prophylactically at a dose of 5 microg/kg/d subcutaneously . In both groups , the planned interval between chemotherapy courses was a minimum of 21 days . We report here interim results of 34 patients . The incidence of febrile neutropenia ( absolute neutrophil count < 0.5 x 10(9)/L and oral temperature > or = 38.5 degrees C ) was 17 % in children receiving r-metHuG-CSF , as compared with 40 % in the control group ( P = .007 ) . In addition , the median total duration of febrile neutropenia was reduced from 20.3 to 6.2 days per patient ( P = .02 ) . Culture-confirmed infections occurred less frequently in the r-metHuG-CSF group ( 8 % v 15 % ; P = .04 ) , and the total duration of intravenous antibiotic use was significantly reduced from 32.2 days to 18.2 days per patient ( P = .02 ) . A tighter adherence to the planned treatment schedule was also facilitated by r-metHuG-CSF ( P = .007 ) . With a median follow-up of 3.3 years , the estimated EFS of 4 years is 41 % + /- 12 % . In conclusion , r-metHuG-CSF administered prophylactically in the interval between chemotherapy courses significantly reduced febrile neutropenia , culture-confirmed infections , and duration of intravenous antibiotic administration and allowed for tighter adherence to the treatment schedule BACKGROUND R and omized trials of colony-stimulating factors in febrile patients with neutropenia after chemotherapy have not consistently shown clinical benefit . Nevertheless , the use of colony-stimulating factors to treat patients with chemotherapy-induced neutropenia is widespread . METHODS We performed a r and omized , double-blind , placebo-controlled trial of granulocyte colony-stimulating factor ( G-CSF ) in afebrile out patients with severe chemotherapy-induced neutropenia . We measured the number of days of neutropenia , rate of hospitalization , number of days in the hospital , number of days the patient received parenteral antibiotics , and number of culture-positive infections . RESULTS We r and omly assigned 138 patients to receive G-CSF ( n=71 ) or placebo ( n=67 ) . The median time to an absolute neutrophil count of at least 500 per cubic millimeter was significantly shorter for patients who received G-CSF ( two days , vs. four days for the patients given placebo ) . However , there was no effect on the rate of hospitalization , number of days in the hospital , duration of treatment with parenteral antibiotics , or number of culture-positive infections . CONCLUSIONS Routine therapeutic application of G-CSF in afebrile patients with severe neutropenia can reduce the duration of neutropenia , but this does not appear to provide practical clinical benefit Purpose : To examine the effect of levofloxacin prophylaxis on infection rates during chemotherapy with docetaxel plus carboplatin in elderly patients with advanced non-small cell lung cancer . Methods : In a r and omized , double-blind , phase III study , patients ( ≥65 years ) with untreated , histologically/cytologically proven stage IIIB/IV non-small cell lung cancer received docetaxel ( 75 mg/m2 ) plus carboplatin ( area under the curve 6 ) on day 1 every 3 weeks , plus once-daily levofloxacin ( 500 mg orally ) or placebo on days 5 to 11 . The primary end point was the rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics . Secondary end points included overall infection rate , toxicity , overall survival , and progression-free survival . Results : In total , 187 patients were r and omized to levofloxacin ( n = 95 ) or placebo ( n = 92 ) . The rate of grade 3/4 infections or grade 1/2 infections treated with additional antibiotics ( intent-to-treat population ) was 27.5 % ( 95 % confidence interval , 19.3–39.0 % ) for levofloxacin versus 36.7 % ( 95 % confidence interval , 27.1–48.0 % ) for placebo . Median time to first infection was 67 days for levofloxacin versus 46 days for placebo . Grade 3/4 infections occurred in 8.8 % of patients in the levofloxacin group versus 26.7 % for placebo . There was one grade 5 infection in each group . Grade ≥3 toxicities ( levofloxacin versus placebo ) included leukopenia ( 63.2 versus 52.2 % ) , neutropenia ( 62.1 versus 51.1 % ) , dyspnea ( 12.6 versus 8.7 % ) , and pain ( 10.5 versus 9.8 % ) . There was no significant difference in overall survival or progression-free survival between groups . Conclusions : Levofloxacin prophylaxis reduces the rate of infection compared with placebo and is well tolerated in elderly patients receiving docetaxel plus carboplatin BACKGROUND The role of prophylactic antibacterial agents after chemotherapy remains controversial . METHODS We conducted a r and omized , double-blind , placebo-controlled trial in patients who were receiving cyclic chemotherapy for solid tumors or lymphoma and who were at risk for temporary , severe neutropenia ( fewer than 500 neutrophils per cubic millimeter ) . Patients were r and omly assigned to receive either 500 mg of levofloxacin once daily or matching placebo for seven days during the expected neutropenic period . The primary outcome was the incidence of clinical ly documented febrile episodes ( temperature of more than 38 degrees C ) attributed to infection . Secondary outcomes included the incidence of all probable infections , severe infections , and hospitalization but did not include a systematic evaluation of antibacterial resistance . RESULTS A total of 1565 patients underwent r and omization ( 784 to placebo and 781 to levofloxacin ) . The tumors included breast cancer ( 35.4 percent ) , lung cancer ( 22.5 percent ) , testicular cancer ( 14.4 percent ) , and lymphoma ( 12.8 percent ) . During the first cycle of chemotherapy , 3.5 percent of patients in the levofloxacin group had at least one febrile episode , as compared with 7.9 percent in the placebo group ( P<0.001 ) . During the entire chemotherapy course , 10.8 percent of patients in the levofloxacin group had at least one febrile episode , as compared with 15.2 percent of patients in the placebo group ( P=0.01 ) ; the respective rates of probable infection were 34.2 percent and 41.5 percent ( P=0.004 ) . Hospitalization was required for the treatment of infection in 15.7 percent of patients in the levofloxacin group and 21.6 percent of patients in the placebo group ( P=0.004 ) . The respective rate of severe infection was 1.0 percent and 2.0 percent ( P=0.15 ) , with four infection-related deaths in each group . An organism was isolated in 9.2 percent of probable infections . CONCLUSIONS Among patients receiving chemotherapy for solid tumors or lymphoma , the prophylactic use of levofloxacin reduces the incidence of fever , probable infection , and hospitalization BACKGROUND To determine whether the cost of prophylactic antibiotics during chemotherapy is offset by cost savings due to a decreased incidence of febrile leukopenia ( FL ) . PATIENTS AND METHODS Small-cell lung cancer ( SCLC ) patients were r and omised to st and ard or intensified chemotherapy with granulocyte colony-stimulating factor to assess the impact on survival ( n = 244 ) . In addition , patients were r and omised to prophylactic ciprofloxacin and roxithromycin or placebo to assess the impact on FL ( n = 161 ) . The economic evaluation examined the costs and effects of patients taking antibiotics versus placebo . Medical re source utilisation was documented prospect ively , including 33 patients from one centre in The Netherl and s ( NL ) and 49 patients from one centre in Germany ( GE ) . The evaluation takes the perspective of the health insurance systems and of the hospitals . Sensitivity analyses were performed . RESULTS In the main trial , prophylactic antibiotics reduced the incidence of FL , hospitalisation due to FL and use of therapeutic antibiotics by 50 % . In GE , the incidence of FL was not reduced by prophylaxis . This result ed in an average cost difference of only 35 Euros [ 95 % confidence interval ( CI ) (-)1.713 - 2.263 ] in favour of prophylaxis ( not significant ) . In NL , prophylaxis reduced the incidence of FL by nearly 50 % , comparable with the results of the main trial , result ing in a cost difference of 2706 Euros [ 95 % CI 810 - 5948 ] , demonstrating savings in favour of prophylactic antibiotics of nearly 45 % . Sensitivity analyses indicate that with an efficacy of prophylaxis of 50 % , and with expected costs of antibiotic prophylaxis of 500 Euros or less , cost savings will incur over a broad range of baseline risks for FL ; that is , a risk > 10 - 20 % for FL per cycle . CONCLUSIONS Giving oral prophylactic antibiotics to SCLC patients undergoing chemotherapy is the dominant strategy in both GE and NL , demonstrating both cost-savings and superior efficacy . The sensitivity analyses demonstrate that , due to the efficacy of prophylactic antibiotics and their low unit cost , cost savings will incur over a broad range of baseline risks for FL . We recommend the use of prophylactic antibiotics in patients at risk for FL during chemotherapy BACKGROUND Recombinant human granulocyte colony-stimulating factor PO1 CA-20180ilgrastim ) hastens the recovery from neutropenia after P30 CA-21765emotherapy , but its role in the management of childhood leukemia is unclear . METHODS We r and omly assigned 164 patients with acute lymphoblastic leukemia ( age range , 2 months to 17 years ) to receive placebo or G-CSF ( 10 microg per kilogram of body weight per day subcutaneously ) , beginning one day after the completion of remission-induction therapy and continuing until the neutrophil count was greater than or equal to 1000 per cubic millimeter for two days . The clinical and laboratory effects of this therapy were documented for 21 days . The area under the plasma G-CSF concentration-time curve was measured on days 1 and 7 in both groups . RESULTS Responses to the growth factor could be assessed in 148 patients ( 73 in the G-CSF group and 75 in the placebo group ) . G-CSF treatment did not significantly lower the rate of hospitalization for febrile neutropenia ( 58 percent in the G-CSF group vs. 68 percent in the placebo group ; relative risk , 0.85 ; 95 percent confidence interval , 0.59 to 1.16 ) , increase the likelihood of event-free survival at three years ( 83 percent in both groups ) , or decrease the number of severe infections ( five in the G-CSF group vs. six in the placebo group ) . Patients treated with G-CSF had shorter median hospital stays ( 6 days vs. 10 days , P=0.011 ) and fewer documented infections ( 12 vs. 27 , P=0.009 ) . The median total costs of supportive care were similar in the G-CSF and placebo groups ( $ 8,768 and $ 8,616 , respectively ) . Among patients who did not have febrile neutropenia during the first week of G-CSF or placebo injections , higher systemic exposure to the growth factor on day 7 was significantly related to a lower probability of subsequent hospitalization ( P=0.049 ) . CONCLUSIONS G-CSF treatment had some clinical benefit in children who received induction chemotherapy for acute lymphoblastic leukemia , but it did not reduce the rate of hospitalization for febrile neutropenia , prolong survival , or reduce the cost of supportive care Sixty-four untreated adult acute lymphoblastic leukemia ( ALL ) patients were r and omized to receive chemotherapy alone , n = 31 or chemotherapy and granulocyte colony stimulating factor ( G-CSF ) , n = 33 . During induction patients received G-CSF for 5 days between four weekly Epirubicin+Vcr administrations , starting 36 h after each application and finishing 48 h before the next one with the intention to possibly generate a cell cycle dependent protection of normal hematopoietic progenitors and to stimulate granulopoiesis . The complete remission ( CR ) rate equaled 94 % in the G-CSF group and 87 % in controls . Patients who received G-CSF , if compared to the controls , had shorter granulocytopenia during induction and consolidation , displayed a lower infection rate , completed the induction-consolidation quicker and stayed shorter in hospital during induction , p < 0.001 - 0.04 . Follow-up at 2 years revealed a rather higher probability of survival ( 59 vs. 27 % , p = 0.04 ) and a lower relapse rate ( 32 vs. 60 % ) in G-CSF arm than in controls . The beneficial influence of G-CSF administered in time-sequenced fashion on survival needs further confirmation Summary Three hundred and forty-two patients with hematological malignancies underwent allogeneic marrow transplantation from family donors and were allocated to receive 1 ) no specific infection prophylaxis in a conventional hospital room ( control , 100 patients ) , 2 ) prophylactic systemic antibiotics ( PSA ) in a conventional hospital room ( PSA group , 101 patients ) , 3 ) decontamination and isolation in a laminar air flow ( LAF ) room ( LAF group , 65 patients ) and 4 ) PSA in an LAF room ( LAF+PSA group , 76 patients ) . Patients were studied for bacterial and fungal complications from the day of admission and until engraftment . LAF isolation was discontinued before engraftment in 27 % ( LAF+PSA group ) to 32 % ( LAF group ) of isolated patients . PSA was not given according to protocol in 26 % ( LAF+PSA group ) to 27 % ( PSA group ) of patients on prophylactic antibiotics . Septicemia occurred in 41 % , 22 % , 25 % and 10 % of patients in the control , PSA , LAF and LAF + PSA group , respectively . The incidence of septicemia was significantly less in the LAF + PSA group than in the control and LAF group with the incidence of septicemia significantly higher in the control group than in any of the other three groups . No other risk factors analyzed in proportional hazards regression tests were associated with septicemia acquisition . It is concluded that effective infection prevention modalities significantly reduce infection morbidity in transplant patients . Since most granulocytopenic transplant patients not receiving PSA will receive empiric or therapeutic broad spectrum antibiotics , the use of PSA in or out of LAF isolation is recommended as an effective modality to reduce septicemia acquisition . ZusammenfassungBei 341 Patienten mit malignen hämatologischen Erkrankungen wurde eine allogene Knochenmarkstransplantation von Spendern aus der Familie durchgeführt . Die Patienten wurden den folgenden Studienarmen zugeordnet : 1 ) Keine spezifische Infektionsprophylaxe , Pflege in einem konventionellen Krankenzimmer ( Kontrollen , 100 Patienten ) ; 2 ) Systemische Antibiotikaprophylaxe ( PSA ) in konventionellem Krankenzimmer ( 101 Patienten ) ; 3 ) Dekontamination und Isolation in einem Laminar Air Flow(LAF)-Raum ( 65 Patienten ) und 4 ) PSA in einem LAF-Raum ( 76 Patienten ) . Vom Tag der Einweisung bis zur Transplantation wurden die Patienten auf Komplikationen durch bakterielle und Pilzinfektionen untersucht . Vor der Transplantation wurde die LAF-Isolation bei 27 % der LAF plus PSA-Gruppe und bei 32 % der LAF-Gruppe abgebrochen . Entsprechend Protokoll erhielten 26 % der LAF plus PSA und 27 % der PSA-Gruppe die Antibiotikaprophylaxe nicht . Septikämien traten bei 41 % der Patienten der Kontrollgruppe , 22 % der mit PSA in konventioneller Pflegeeinheit , bei 25 % der in LAF-Räumen beh and elten und bei 10 % der in LAF-Räumen gepflegten und zusätzlich mit PSA beh and elten Patienten auf . Die Septikämie-Inzidenz war unter LAF mit PSA signifikant geringer als in der Kontrollgruppe und der in LAF-Isolation gepflegten Patientengruppe ; zugleich war die Septikämie-Inzidenz in der Kontrollgruppe signifikant höher als in einer der drei and eren Gruppen . Die proportionale Risiko-Regressionsanalyse ergab keine zusätzlichen Risikofaktoren für das Auftreten einer Septikämie . Wirksame Maßnahmen zur Infektionsprophylaxe können folglich die Infektionsmorbidität bei Transplantatempfängern signifikant vermindern . Da die meisten granulozytopenischen Transplantatempfänger eine empirische oder gezielte Therapie mit Breitspektrumantibiotika erhalten , wird die PSA unabhängig von LAF-Isolation als effektive Maßnahme zur Verminderung der Septikämien empfohlen Granulocyte colony‐stimulating factor ( G‐CSF ) is widely used following myeloablative chemotherapy ( high‐dose therapy ; HDT ) and peripheral blood progenitor cell rescue ( PBPCR ) to reduce neutrophil engraftment time . The dose and duration required to gain maximum clinical and economic benefit has not been fully investigated . This double blind placebo‐controlled r and omised trial was performed to determine whether short course low‐dose or st and ard‐dose Lenograstim ( L ) would influence recovery of haematopoiesis following HDT and PBPCR . Sixty‐one patients were r and omised between May 1999 and November 2004 , to receive st and ard‐dose lenograstim ( 263 μg/d ) , low‐dose lenograstim ( 105 μg/d ) or placebo injections . These commenced on day + 5 following PBPCR and continued until neutrophil engraftment [ absolute neutrophil count ( ANC ) ] ≥ 0·5 × 109/l . Patients received st and ard supportive care until haemopoietic recovery . Both st and ard‐ and low‐dose lenograstim result ed in a significantly shorter median time to neutrophil recovery ( ANC ≥ 0·1 × 109/l:10·0 vs. 11·0 d , P = 0·025 ; ANC ≥ 0·5 × 109/l:11·0 vs. 14·0 d , P = 0·0002 ) compared with placebo . There was no significant difference in blood product support , antibiotic usage , documented infection , overall survival or relapse‐free survival between the groups . Short course low‐dose lenograstim is as effective as st and ard‐dose in reducing neutrophil engraftment time following HDT and PBPCR In order to assess the potential clinical benefit of filgrastim ( G-CSF ) after peripheral blood stem cell ( PBSC ) autotransplantation a r and omized study was begun in our center in July 1997 : 62 patients were involved ( 30 received filgrastim after PBSC infusion and 32 , the control group , received no cytokines ) . All were adults ( median 40 years , range 18–65 ) . Patients with one of three different pathologies were recruited : 28 had advanced breast carcinoma , 23 had lymphomas ( 12 Hodgkin ’s disease and 11 non-Hodgkin ’s lymphoma ) and 11 had de novo AML . All of them were transplanted using myeloablative chemotherapy conditioning regimens . G-CSF was administered subcutaneously from day + 5 in the treated group at a dose of 5 μg/kg body weight/day . The numbers of CD34 + and mononuclear ( MNC ) cells infused were similar in each group . Only minor differences regarding the use of G-CSF could be inferred from the analysis of the data . Faster granulocyte engraftment was evident in the treated group ( mean of 10 vs 12 days to achieve > 0.5 × 109/l granulocytes , P = 0.0008 ) , without differences in incidence and severity of infections , days of fever or duration of antibiotic treatment between groups . There was slightly slower platelet engraftment ( mean of 15 days in the group with G-CSF vs 12 days in the other group to achieve > 20 × 109/l platelets , P = NS ) in this series , but there were no differences in incidence and severity of haemorrhage or platelet transfusion support . Considering the economical costs , the median expenditure per inpatient stay was Eur5961 ( range Eur4386–Eur17186 ) in the G-CSF group compared with Eur5751 ( range Eur3676–Eur15640 ) in the control group ( P = 0.47 ) . From our data it could be concluded that for adult patients transplanted with PBSC there is no clear beneficial impact of post-infusion G-CSF administration Abstract This study compared two recombinant human ( rh ) hematopoietic growth factors in healthy volunteers for stem cell stimulation . Granulocyte colony-stimulating factor ( G-CSF , n=9 ) or granulocyte-macrophage colony-stimulating factor ( GM-CSF , n=8 ) was given subcutaneously for 5 days ( 5 μg/kg/day ) . Controls ( n=5 ) received no growth factor . Laboratory parameters and side effects were monitored for 8 days . Within 24 h , both cytokines led to a rapid increase of leukocytes , the majority of which were granulocytes . Compared with the controls ( n=5 ) , the increase on day 5 in the G-CSF/GM-CSF groups was 37-/10-fold ( CD34 + cells ) , 5.2-/2.4-fold ( leukocytes ) , 7.2-/3.0-fold ( granulocytes ) , 7.4-/4.4-fold ( monocytes ) , 1.7-/1.1-fold ( lymphocytes ) , 9.8-/2.7-fold ( basophils ) , 2.3-/9.6-fold ( eosinophils ) , and 1.9-/1.6-fold ( reticulocytes ) . The mobilization of myeloblasts , promyelocytes , myelocytes , and metamyelocytes coincided with the pronounced increase of CD34 + PBPC observed on day 4 . Serum levels of uric acid ( UA ) and lactic dehydrogenase ( LDH ) increased under G-CSF , and platelets decreased after G-CSF discontinuation . Rash at the injection site occurred in 50 % of the GM-CSF-treated volunteers . Seven volunteers in the GM-CSF group and six in the G-CSF cohort complained of flu-like symptoms , including musculoskeletal pain . We conclude that , in terms of tolerance and mobilization of CD34 + cells and leukocytes , G-CSF is superior to GM-CSF , but higher levels of UA and LDH and late decrease in platelets make monitoring of these parameters necessary Considerable morbidity , mortality , and economic costs result during remission induction therapy for elderly patients with acute myeloid leukemia ( AML ) . In this study , the economic costs of adjunct granulocyte colony stimulating factor ( G-CSF ) are estimated for AML patients > 55 years of age who received induction chemotherapy on a recently completed Southwest Oncology Group study ( SWOG ) . Clinical data were based on Phase III trial information from 207 AML patients who were r and omized to receive either placebo or G-CSF post-induction therapy . Analyses were conducted using a decision analytic model with the primary source of clinical event probabilities based on in-hospital care with or without an active infection requiring intravenous antibiotics . Estimates of average daily costs of care with and without an infection were imputed from a previously reported economic model of a similar population . When compared to AML patients who received placebo , patients who received G-CSF had significantly fewer days on intravenous antibiotics ( median 22 vs. 26 , p = 0.05 ) , whereas overall duration of hospitalization did not differ ( median 29 days ) . The median cost per day with an active infection that required intravenous antibiotics was estimated to be $ 1742 , whereas the median cost per day without an active infection was estimated to be $ 1467 . Overall , costs were $ 49,693 for the placebo group and $ 50,593 for the G-CSF patients . G-CSF during induction chemotherapy for elderly patients with AML had some clinical benefits , but it did not reduce the duration of hospitalization , prolong survival , or reduce the overall cost of supportive care . Whether the benefits of G-CSF therapy justify its use in individual patients with acute leukemia for the present remains a matter of clinical judgment Summary : This prospect i ve and r and omized study was conducted to evaluate clinical and economic consequences of using granulocyte colony-stimulating factor ( G-CSF ) following autologous peripheral blood progenitor cell ( PBPC ) transplantation in children . Between January 1999 and December 2003 , 117 patients underwent autologous PBPCT : 51 patients received G-CSF following PBPCT , while 66 patients did not receive G-CSF . Median time to absolute neutrophil count > 0.5 × 109/l was 10 days in the treatment group and 11 days in the control group ( P<0.009 ) . The median time to platelets > 20 × 109/l was 12 days in both groups ( P = NS ) . The median time to platelets > 50 × 109/l was 15 days in the G-CSF group and 14 days in the control group ( P<0.005 ) . In patients who received < 5 × 106/kg CD34 + cells , the median time to platelets > 20 × 109/l and > 50 × 109/l was similar with or without G-CSF ( 12 and 15 days , respectively ) . Platelet transfusion requirements were lower in the control group ( 2 vs 3 U in G-CSF group ) . There was a trend towards higher total costs with G-CSF : 8146.82 euros and 7873.34 euros with and without G-CSF , respectively ( P=0.1 ) . Our data suggest that there is no indication of the st and ard application of G-CSF in children following PBPC transplantation . The only possible indication is the group of patients with a lower yield of CD34 + cells One hundred and fifty‐seven patients undergoing high‐dose chemotherapy ( HDT ) and autologous stem‐cell transplantation ( ASCT ) for hematopoietic malignancies and solid tumors were r and omly assigned to receive ( Group A ) or not ( Group B ) prophylaxis with ciprofloxacin , orally , and vancomycin , intravenously . Prophylactic antibiotics were given from day 0 until resolution of neutropenia or the appearance of a febrile event . Furthermore , patients in both groups received once a day fluconazole , orally . The primary end‐point of our study was the incidence of neutropenic febrile episodes attributed to infection . One hundred and twelve ( 71.3 % ) patients developed neutropenic fever , 50 ( 56.2 % ) in Group A and 62 ( 91.2 % ) in Group B ( P < 0.001 ) with the majority ( 82 % ) of patients developing fever of unknown origin . Patients on prophylactic antibiotics had a significantly lower rate of bacteremias ( 5.6 % ) than did those r and omized to no prophylaxis ( 29.4 % ) ( P = 0.005 ) and , when developing neutropenic fever , they had a lower probability of response to first‐line empirical antibiotics ( P = 0.025 ) . Prophylactic administration of ciprofloxacin and vancomycin reduced the incidence of neutropenic fever in patients receiving HDT with ASCT , however , without affecting the total interval of hospitalization , time to engraftment , or all‐cause mortality . Therefore , our results do not support the use of antibiotic prophylaxis for patients undergoing HDT and ASCT . Am . J. Hematol . , 2010 . © 2010 Wiley‐Liss , G-CSF accelerates neutrophil recovery after autologous peripheral blood progenitor cell transplantation ( aPBPCT ) , although the optimal timing for its administration is currently unknown . In order to establish the role and the optimal timing of administration of G-CSF after immunoselected CD34 + aPBPCT , we analyzed the data from 21 consecutive patients affected by haematological malignancies . Patients were r and omized into three groups according to G-CSF administration after transplantation : day + 1 ( group B ) ; day + 7 ( group C ) or no G-CSF ( group A ) . Serum G-CSF level was evaluated until engraftment . The CD34 + cell dose reinfused was similar ( P = 0.48 ) . G-CSF significantly reduced time to recovery of PMN > 0.5 × 109/l ( 11 vs 14 vs 20.5 days ) ( P = 0.00046 ) ; > 1.0 × 109/l ( 12 vs 15 vs 22 ) ( P = 0.001 ) . No difference was observed in the number of days with PMN < 0.1 × 109/l ( 5.5 vs 7 vs 8 days ) . Platelet count > 50 × 109/l and > 100 × 109/l , reticulocytes > 1 % , length of hospitalization , non-prophylactic antibiotic therapy , fever , incidence of sepsis and transfusion support did not differ . Early or delayed G-CSF after immunoselected CD34 + aPBPCT significantly accelerated PMN recovery but did not reduce the amount of supportive treatment or the duration of hospitalization . Delaying the initiation of G-CSF did not reduce the length of treatment ( 11.5 vs 12 days ) . Early or delayed G-CSF administration result ed in G-CSF peak serum levels 7 (early)–12 (delayed)-fold greater than an endogenous response to neutropenia Blood stem cell transplantation ( BSCT ) results in rapid hematopoietic recovery in both the allogeneic and autologous transplant setting s. Because of the large numbers of progenitor cells in mobilized blood , the administration of growth factors after transplantation may not provide further acceleration of hematopoietic recovery . A r and omized , double-blind , placebo-controlled study was performed to determine the effects of filgrastim ( granulocyte colony-stimulating factor ; G-CSF ) administration on hematopoietic recovery after allogeneic BSCT . Fifty-four patients with hematologic malignancies undergoing a related , HLA-matched allogeneic BSCT were r and omly assigned to receive daily filgrastim at 10 microg/kg or placebo starting on the day of transplantation . A minimum of 3 x 10(6 ) CD34(+ ) cells/kg in the allograft was required for transplantation . All patients received a st and ard preparative regimen and a st and ard regimen for the prevention of graft-versus-host disease ( GVHD ) . The median time to achieve an absolute neutrophil count greater than 0.5 x 10(9)/L was 11 days ( range , 9 - 20 days ) for patients who received filgrastim compared with 15 days ( range , 10 - 22 days ) for patients who received placebo ( P = .0082 ) . The median time to achieve a platelet count greater than 20 x 10(9)/L was 13 days ( range , 8 - 35 days ) for patients who received filgrastim compared with 15.5 days ( range , 8 - 42 days ) for patients who received placebo ( P = .79 ) . There were no significant differences for red blood cell transfusion independence , the incidence of acute GVHD , or 100-day mortality between the groups . The administration of filgrastim appears to be a safe and effective supportive-care measure following allogeneic BSCT PURPOSE To determine whether the use of a recombinant human granulocyte colony-stimulating factor ( [ G-CSF ] lenogastrim ) can increase the chemotherapy dose-intensity ( CDI ) delivered during consolidation chemotherapy of childhood acute lymphoblastic leukemia ( ALL ) . PATIENTS AND METHODS Sixty-seven children with very high-risk ALL were r and omized ( slow early response to therapy , 55 patients ; translocation t(9;22 ) or t(4;11 ) , 12 patients ) . Consolidation consisted of six courses of chemotherapy ; the first , third , and fifth courses were a combination of high-dose cytarabine , etoposide , and dexamethasone ( R3 ) , whereas the second , fourth , and sixth courses included vincristine , prednisone , cyclophosphamide , doxorubicin , and methotrexate ( COPADM ) . G-CSF was given after each course , and the next scheduled course was started as soon as neutrophil count was > 1 x 10(9)/L and platelet count was > 100 x 10(9)/L. CDI was calculated using the interval from day 1 of the first course to hematologic recovery after the fifth course ( 100 % CDI = 105-day interval ) . RESULTS CDI was significantly increased in the G-CSF group compared with the non-G-CSF group ( mean + /- 95 % confidence interval , 105 + /- 5 % v 91 + /- 4 % ; P < .001 ) . This higher intensity was a result of shorter post-R3 intervals in the G-CSF group , whereas the post-COPADM intervals were not statistically reduced . After the R3 courses , the number of days with fever and intravenous antibiotics and duration of hospitalization were significantly decreased by G-CSF , whereas reductions observed after COPADM were not statistically significant . Duration of granulocytopenia was reduced in the G-CSF group , but thrombocytopenia was prolonged , and the number of platelet transfusions was increased . Finally , the 3-year probability of event-free survival was not different between the two groups . CONCLUSION G-CSF can increase CDI in high-risk childhood ALL . Its effects depend on the chemotherapy regimen given before G-CSF administration . In our study , a higher CDI did not improve disease control Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) was administered to 40 pediatric patients undergoing partially matched related , or closely matched unrelated , allogeneic marrow transplants . This trial was set up in a prospect i ve , r and omized , double-masked , placebo-controlled manner to establish if the administration of GM-CSF to such patients enhanced neutrophil recovery in this allogeneic transplant setting . The GM-CSF group had a significantly shorter time to neutrophil recovery to > 500 x 10(9 ) cells/L ( 15 days ) than the placebo group ( p = 0.0036 ) . In addition , the GM-CSF group had a significantly shorter neutrophil recovery time to > 1,000 x 10(9 ) cells/L ( 18 days ) than the placebo group ( p = 0.0053 ) . The primary objective of this study was met by showing that GM-CSF enhanced neutrophil recovery in this allogeneic setting . However , within the study group of patients , there was no effect of GM-CSF on the incidence or severity of graft-vs.-host disease ( GvHD ) , one of the secondary end-points of the study . With regard to the other secondary end-points , there was no effect of GM-CSF on marrow cellularity , duration of systemic antibiotics given for real infections or as prophylaxis to prevent infections , risk of significant infections ( as defined by systemic culture of virus , fungus , or bacteria ) , and duration or cost of hospitalization , platelet recovery , and nutritional support . With the secondary end-points , it will be necessary to study larger numbers of pediatric patients to identify differences that are small in this study group . In conclusion , GM-CSF can be safely administered to children with few , if any , significant side-effects . Additional work remains to facilitate earlier discharge of patients and decreased antibiotic usage , to offset the cost of using a neutrophil growth factor A study was carried out to compare the use of prophylactic imipenem administered at the onset of profound neutropenia ( immediate ) with therapeutic imipenem administered at the onset of neutropenic fever ( delayed ) in cancer patients treated with high-dose chemotherapy . A total of 65 patients who were scheduled to receive two cycles of high-dose cyclophosphamide , etoposide , cisplatin ( CEP ) chemotherapy were r and omized to receive imipenem either at presentation of neutropenia ( immediate imipenem arm , prophylactic arm ) or at commencement of neutropenic fever ( delayed imipenem arm , therapeutic arm ) . Treatment was crossed over when the second CEP chemotherapy cycle was received . Of the 65 patients , 41 received the two planned cycles and 24 received only the first . Compared with the delayed imipenem arm , the immediate imipenem arm was associated with lower fever incidence ( 86.3 % vs. 100 % , p=0.0142 ) and Gram-negative bacteria infection [ 4/51 ( 7.8 % ) vs. 14/55 ( 25.5 % ) , OR=0.24 , p = 0.031 ] . There were fewer episodes of pneumonia ( 2 % vs. 12.7 % ) , septic shock ( 0 % vs. 3.6 % ) and deaths from infection ( 0 % vs. 3.6 % ) , but these differences did not reach statistical significance . With regard to delayed imipenem , for every seven patients with immediate imipenem , one episode of febrile neutropenia was avoided ; for every six patients administered immediate imipenem , one case of Gram-negative infection was avoided ; and for every nine patients administered immediate imipenem , one episode of pneumonia was avoided . There were no differences in the incidence of Gram-positive infections nor in the length of hospitalization between the two treatment arms . In conclusion , compared to its conventional delayed use , immediate imipenem significantly reduces the frequency of febrile neutropenia and Gram-negative infections in patients with high-dose chemotherapy Gram-positive bacteria are the most commonly isolated organisms after bone marrow transplantation ( BMT ) and severe streptococcus septicemia has been reported . In order to evaluate the benefit of a gram-positive prophylaxis after BMT , we conducted a prospect i ve , r and omized trial of systemic vancomycin among 60 patients undergoing BMT for hematologic malignancies . Patients were r and omized to receive ( n = 30 ) or not receive ( n = 30 ) prophylactic vancomycin 15 mg/kg every 12 hours from day -2 until resolution of neutropenia or until the first episode of fever . All patients were treated in laminar air-flow rooms , received sterile diet , total gut decontamination , and had central venous catheters placed surgically . Vancomycin was found to be highly effective in preventing gram-positive infections that occurred in 11 of 30 patients in the control group versus zero of 30 in the vancomycin group ( P less than .002 ) . All gram-positive infections occurring in the control group were symptomatic ( nine septicemia and two local infections ) , and one patient with Streptococcus septicemia died with pneumonia . Thus , gram-positive prophylaxis was found to decrease infection morbidity after BMT . Moreover , the number of days with fever ( P less than .001 ) , and empiric antibiotic therapy ( P less than .01 ) was reduced without added toxicity or cost . This study confirmed the high prevalence of gram-positive infections after BMT and emphasized the clinical benefits of an adapted prophylaxis We evaluated the effect of norfloxacin , 400 mg given orally every 12 hours , on the prevention of bacterial infections in 68 adult patients who had acute leukemia throughout prolonged courses of granulocytopenia ( median , 32 days ) . Gram-negative infections were documented in 13 of the 33 patients receiving placebo , but only in 4 of the 35 patients receiving norfloxacin ; no effect on the frequency of gram-positive or fungal infections was noted . Norfloxacin administration result ed in the suppression of gastrointestinal tract colonization by aerobic bacteria without the development of norfloxacin resistance . Patients receiving norfloxacin developed first infectious fevers later than did those receiving placebo , had more rapid resolution of that fever after systemic antibiotic treatment , and spent less time febrile . Therefore , although no difference was seen in survival duration , we found that the prophylactic administration of oral norfloxacin led to decreases in overall morbidity and gram-negative infections , was well tolerated , and did not predispose to the development of multiply drug-resistant bacteria OBJECTIVES To explore the safety and effectiveness of the individually determined application granulocyte-colony stimulating factor ( G-CSF ) after autologous peripheral blood stem cell transplantation ( ASCT ) . METHODS The administration of G-CSF from day + 5 ( arm A ) was compared in a r and omised , controlled trial with delayed , individually determined administration ( G-CSF started when WBC > or= 0.5 x 10(9)/L and ANC > or= 0.1 x 10(9)/L or at day + 10 ; arm B ) , and with placebo ( arm C ) . RESULTS One hundred and six patients , median age 45 ( range 21 - 64 ) , all with malignant lymphoma treated with BEAM chemotherapy were analysed . A significant difference in the time to neutrophil engraftment and in the duration of neutropenia < 0.5 x 10(9)/L and < 1.0 x 10(9)/L was observed between the arms ( P = 0.04-<0.0001 ) with a 1-d prolongation of the median duration s in arm B in comparison with arm A but a 2 - 4-d prolongation in the placebo arm C in comparison with arm B. The median number and range of days to neutrophil engraftment > 0.5 x 10(9)/L after graft re-infusion was 10 ( 9 - 14 ) in arm A ; 11 ( 9 - 19 ) in arm B ; and 14 ( 10 - 30 ) in arm C ( P < 0.0001 ) . Engraftment of platelets to > 20 x 10(9)/L and > 50 x 10(9)/L was significantly delayed in the arms using G-CSF in comparison with placebo ( P = 0.04 - 0.002 ) without any increase in bleeding or in transfusion requirement . There was no difference in the incidence and duration of transplant-related complications and their treatment between the arms . CONCLUSIONS Our study has confirmed the safety of individually determined administration of G-CSF . The optimal timing of G-CSF application after ASCT in patients with good- quality grafts is shortly before expected spontaneous engraftment A prospect i ve study was carried out in 44 patients treated by intensive chemotherapy inducing a prolonged neutropenia ( granulocytes less than 0.5.10(9)/l ) . All the patients were isolated in protected rooms , received a pathogen-free diet and nonabsorbable oral antibiotics . After double-blind r and omization , 22 patients received 2 g of Ceftriaxone ( Cef ) in a daily infusion beginning on the first day of chemotherapy ; and 22 patients received 2 g of placebo ( P ) under the same conditions . Prophylaxis was continued until the neutropenia resolved ( granulocytes greater than 0.5.10(9)/l ) or until the onset of infectious symptoms . 19 patients in each group developed febrile episodes , occurring significantly later in the Cef group ( 16.6 days versus 10.6 days in the P group ) . No Cef-resistant organism was isolated . Finally , the time at which apyrexia was obtained after the beginning of curative antibiotherapy was the same in both groups . The routine intravenous administration of Cef in combination with nonabsorbable antibiotics is a useful approach in reducing the risk of infection in the neutropenic host PURPOSE Febrile neutropenia ( FN ) is a major complication of chemotherapy . Antibiotics as well as granulocyte colony-stimulating factor ( G-CSF ) are effective in preventing FN . This multicenter r and omized phase III trial determines whether the addition of G-CSF to antibiotic prophylaxis can further reduce the incidence of FN in patients with small-cell lung cancer ( SCLC ) at the risk of FN . PATIENTS AND METHODS Patients ( N = 175 ) were stratified for stage of disease , performance status , age , and prior chemotherapy treatment , and were r and omly assigned for treatment with cyclophosphamide , doxorubicin , and etoposide ( CDE ) , followed by prophylactic antibiotics alone ( ciprofloxacin and roxithromycin ) or by antibiotics in combination with G-CSF on days 4 to 13 . RESULTS In cycle 1 , 20 patients ( 24 % ) in the antibiotics group developed FN compared with nine patients ( 10 % ) in the antibiotics plus G-CSF group ( P = .01 ) . In cycles 2 to 5 , the incidences of FN were practically the same in both groups ( 17 % v 11 % ) . Only the treatment parameters ( odds ratio , 0.33 ; 95 % CI , 0.14 to 0.78 ) and age ( 1.067 per year ; 95 % CI , 1.013 to 1.0124 ) were related to the probability of FN in cycle 1 . CONCLUSION Primary G-CSF prophylaxis added to primary antibiotic prophylaxis is effective in reducing FN and infections in SCLC patients at the risk of FN with the first cycle of CDE chemotherapy . For patients with similar risk of FN , the combined use of prophylactic antibiotics plus G-CSF can be considered , specifically in the first cycle of chemotherapy BACKGROUND Despite the current widespread use of prophylactic G-CSF in children with solid tumours and leukaemia , its effectiveness has not been clearly demonstrated . This r and omised study evaluates the role of G-CSF given after a 5-day intensification block in children with acute lymphoblastic leukaemia ( ALL ) . PROCEDURE Forty-six children with ALL or T-Cell non-Hodgkins lymphoma ( NHL ) treated on MRC ALL 97 , UKALL XI or UKCCSG 9504 NHL protocol s were r and omised to receive granulocyte colony-stimulating factor following either the first or the second block of intensive chemotherapy in a cross-over study to determine if the prophylactic administration of G-CSF could reduce the rate of readmission to hospital for management of febrile neutropenia . RESULTS There was a statistically significant difference in the rate of hospital admission in the group receiving prophylaxis , with 34 of 46 being admitted , compared to 42 of 46 patients in the control arm ( 74 vs. 91 % ; P=0.0386 ) . There were no differences found in duration of hospital admission , haematological toxicity , neutrophil recovery or duration of supportive care between the two groups . There was no demonstrable cost benefit derived from the prophylactic administration of G-CSF . CONCLUSIONS This study shows that the prophylactic administration of G-CSF following intensification chemotherapy for childhood ALL and T-NHL produces a significant reduction in the rate of readmission to hospital for the management of febrile neutropenia PURPOSE To compare the efficacy and safety of recombinant human granulocyte colony-stimulating factor ( rHuG-CSF ) versus its inert vehicle in patients with unilateral nonmetastatic inflammatory breast cancer treated with fluorouracil , epirubicin , and cyclophosphamide high-dose ( FEC-HD ) neoadjuvant chemotherapy . PATIENTS AND METHODS One hundred twenty patients have been enrolled by nine French centers in this double-blind , parallel-group , vehicle-controlled study to compare at each cycle subcutaneous lenograstim ( 5 micrograms/kg/d ) with placebo given from day 6 to day 15 after the induction chemotherapy ( day 1 to day 4 , fluorouracil 750 mg/m2 continuous intravenous [ IV ] infusion ; day 2 to day 4 , epirubicin 35 mg/m2 and cyclophosphamide 400 mg/m2 both IV push ) . Four cycles were planned every 3 weeks before locoregional treatment . Patients with febrile neutropenia remained blinded for the subsequent cycles . RESULTS Lenograstim significantly reduced the duration of neutropenia at less than 0.5 x 10(9)/L and less than 1 x 10(9)/L to a median duration of 2 and 3 days , respectively , as compared with 5 and 7 days in the placebo group . This translated into a statistically significant reduced incidence of microbiologically documented infections , and a decreased need for rehospitalizations for infectious events and antibiotic use . Clinical objective tumor response rate observed after four cycles was 89.6 % and 93 % , respectively , in the placebo and treated groups . Mild transient bone and injection-site pain , myelemia , and hyperleukocytosis were the most frequently reported adverse events associated with lenograstim . CONCLUSION Lenograstim is safe and effective to reduce morbidity associated with FEC-HD neoadjuvant chemotherapy in inflammatory breast cancer . Response rate is not affected PURPOSE To reduce the incidence of febrile neutropenia during rapid COJEC ( cisplatin , vincristine , carboplatin , etoposide , and cyclophosphamide given in a rapid delivery schedule ) induction . In the High-Risk Neuroblastoma-1 ( HR-NBL1 ) trial , the International Society of Paediatric Oncology European Neuroblastoma Group ( SIOPEN ) r and omly assigned patients to primary prophylactic ( PP ) versus symptom-triggered granulocyte colony-stimulating factor ( GCSF ; filgrastim ) . PATIENTS AND METHODS From May 2002 to November 2005 , 239 patients in 16 countries were r and omly assigned to receive or not receive PPGCSF . There were 144 boys with a median age of 3.1 years ( range , 1 to 17 years ) of whom 217 had International Neuroblastoma Staging System ( INSS ) stage 4 and 22 had stage 2 or 3 MYCN-amplified disease . The prophylactic arm received a single daily dose of 5 microg/kg GCSF , starting after each of the eight COJEC chemotherapy cycles and stopping 24 hours before the next cycle . Chemotherapy was administered every 10 days regardless of hematologic recovery , provided that infection was controlled . RESULTS The PPGCSF arm had significantly fewer febrile neutropenic episodes ( P = .002 ) , days with fever ( P = .004 ) , hospital days ( P = .017 ) , and antibiotic days ( P = .001 ) . Reported Common Toxicity Criteria ( CTC ) grade d toxicity was also significantly reduced : infections per cycle ( P = .002 ) , fever ( P < .001 ) , severe leucopenia ( P < .001 ) , neutropenia ( P < .001 ) , mucositis ( P = .002 ) , nausea/vomiting ( P = .045 ) , and constipation ( P = .008 ) . Severe weight loss was reduced significantly by 50 % ( P = .013 ) . Protocol compliance with the rapid induction schedule was also significantly better in the PPGCSF arm shown by shorter time to completion ( P = .005 ) . PPGCSF did not adversely affect response rates or success of peripheral-blood stem-cell harvest . CONCLUSION Following these results , PPG-GSF was advised for all patients on rapid COJEC induction PURPOSE To explore the use of SD/01 ( a polyethylene glycol-conjugated filgrastim shown in pre clinical studies to have a prolonged half-life ) in patients with chemotherapy-induced neutropenia . PATIENTS AND METHODS Thirteen patients with non-small-cell lung cancer were r and omized to receive daily filgrastim ( 5 microg/kg/d ) or a single injection of SD/01 ( 30 , 100 , or 300 microg/kg ) 2 weeks before chemotherapy and again 24 hours after administration of carboplatin and paclitaxel . Pharmacodynamic , pharmacokinetic , and safety analyses were performed . RESULTS Peak serum concentrations of SD/01 and the duration of increased serum concentrations were dependent on the SD/01 dose . SD/01 concentrations remained increased longer in patients with chemotherapy-induced neutropenia . Prechemotherapy median absolute neutrophil counts ( ANCs ) in patients receiving SD/01 were increased in a dose-dependent fashion , with the duration of this effect also being dose dependent . After chemotherapy , median ANC nadirs were similar in the filgrastim cohort and the cohort receiving SD/01 30 microg/kg , with higher nadirs seen in the cohorts receiving SD/01 100 or 300 microg/kg . Dose-limiting toxicities were not noted . CD34(+ ) cells were mobilized in all cohorts . CONCLUSION A single dose of SD/01 increases the serum concentration of SD/01 for several days in a dose-dependent fashion and is not associated with significant toxicity . The effects of SD/01 on ANC and CD34(+ ) cell mobilization are comparable or greater than those achieved with daily filgrastim . The self-regulation of this molecule provides a potential therapeutic advantage in a variety of clinical setting s associated with neutropenia This study was design ed to test the hypothesis that administration of granulocyte colony-stimulating factor ( G-CSF ; filgrastim ) during induction chemotherapy with CHOP ( cyclophosphamide , vincristine , doxorubicin , prednisone ) or CNOP ( doxorubicin replaced with mitoxantrone ) in elderly patients with aggressive non-Hodgkin lymphoma ( NHL ) improves time to treatment failure ( TTF ) , complete remission ( CR ) rate , and overall survival ( OS ) . Furthermore , the efficacy of CHOP versus CNOP chemotherapy was compared . A total of 455 previously untreated patients older than 60 years with stages II to IV aggressive NHL were included in the analysis . Patients ( median age , 71 years ; range , 60 - 86 years ) were r and omized to receive CHOP ( doxorubicin 50 mg/m(2 ) ) or CNOP ( mitoxantrone 10 mg/m(2 ) ) with or without G-CSF ( 5 microg/kg from day 2 until day 10 - 14 of each cycle every 3 weeks ; 8 cycles ) . Forty-seven patients previously hospitalized for class I to II congestive heart failure were r and omized to receive CNOP with or without G-CSF ( not included in the CHOP versus CNOP analysis ) . The CR rates in the CHOP/CNOP plus G-CSF and CHOP/CNOP groups were the same , 52 % , and in the CHOP with or without G-CSF and CNOP with or without G-CSF groups , 60 % and 43 % ( P < .001 ) , respectively . No benefit of G-CSF in terms of TTF and OS could be shown ( P = .96 and P = .22 , respectively ) , whereas CHOP was superior to CNOP ( TTF/OS P < .001 ) . The incidences of severe granulocytopenia ( World Health Organization grade IV ) and granulocytopenic infections were higher in patients not receiving G-CSF . The cumulative proportion of patients receiving 90 % or more of allocated chemotherapy was higher ( P < .05 ) in patients receiving G-CSF . Concomitant G-CSF treatment did not improve CR rate , TTF , or OS . Patients receiving CHOP fared better than those given CNOP chemotherapy . The addition of G-CSF reduces the incidence of severe granulocytopenia and infections in elderly patients with aggressive NHL receiving CHOP or CNOP chemotherapy PURPOSE To assess the clinical and economic benefit of low-dose ( 50 microg/m2 ) filgrastim after peripheral blood stem-cell transplantation ( PBSCT ) in a r and omized , placebo-controlled double-blinded study . PATIENTS AND METHODS Thirty-eight patients with lymphoproliferative disorders were r and omized to receive low-dose filgrastim ( 19 patients ) or placebo ( 19 patients ) beginning on the first day after stem-cell reinfusion and continuing until absolute neutrophil count ( ANC ) was greater than 0.5 x 10(9)/L. All patients received greater than 2.5 x 10(6 ) CD34 + cells/kg , which was mobilized with chemotherapy and filgrastim 300 microg from the fifth day . An economic analysis was performed based on the outcome in the two groups . RESULTS Neutrophil engraftment was significantly more rapid in patients who received filgrastim with a median number of days until ANC was greater that 0.5 x 10(9)/L of 10 ( 9 to 13 ) versus 14 ( 9 to 19 ; P < .0001 ) . The time to reach an ANC greater than 1 x 109/L was 12 ( 9 to 14 ) versus 16 days ( 10 to 25 ; P < .0001 ) . The total number of patients who required intravenous antibiotic therapy was lower in the filgrastim-treated group ( 68 % ) compared with the placebo group ( 89 % ) ; also , the median number of days with fever and the duration of antibiotic therapy were shorter , although these differences did not reach statistical significance . However , although only three of 19 ( 16 % ) patients who received filgrastim required amphotericin , 11 of 19 ( 58 % ) who received placebo did require it , and amphotericin usage was significantly less in the filgrastim group ( P = .029 ) . Finally , in-patient stay was significantly shortened in those who received filgrastim from 16 ( 13 to 23 ) to 13 days ( 11 to 18 ; P = .0003 ) . CONCLUSION Low-dose filgrastim significantly reduces neutrophil engraftment time post-PBSCT and also reduces in-patient stay and costs , which makes it economically viable for patients who are undergoing high-dose chemotherapy Preliminary studies in allogeneic BMT suggest that recombinant human granulocyte-macrophage colony-stimulating factor ( rhGM-CSF ) is well tolerated . This is a prospect i ve , multicenter , r and omized , double-blind , placebo-controlled trial . Yeast-derived rhGM-CSF 250 micrograms/m2/day or placebo was administered by 4-hour i.v . infusion starting on the day of marrow infusion ( day 0 ) to day 20 . All patients received HLA-identical sibling marrow and cyclosporine and prednisone for GVHD prophylaxis . Fifty three patients received rhGM-CSF and 56 received placebo . Comparison of demographics revealed no differences . The time to achieve an absolute neutrophil count of > 0.5 x 10(9 ) cells/l was shortened in rhGM-CSF treated patients ( day 13 vs. 17 , P = 0.0001 ) . The incidences of grade III-IV mucositis and infection were significantly reduced ( P = 0.005 , P = 0.001 , respectively ) and duration of hospitalization was modestly shortened by 1 day ( P = 0.02 ) in rhGM-CSF treated patients . No differences in platelet recovery , erythrocyte recovery , incidence of veno-occlusive disease , GVHD severity , relapse or survival were observed . In conclusion , rhGM-CSF is well tolerated and reduces post-transplant morbidity in patients undergoing HLA-identical allogeneic BMT The complete remission ( CR ) rate after intensive chemotherapy for acute myelogenous leukemia ( AML ) remains low in elderly patients , mainly because of a higher infectious mortality rate related to neutropenia and an increased incidence of adverse prognostic factors . Granulocyte-macrophage colony-stimulating factor ( GM-CSF ) has been shown to potentially recruit leukemic blasts into cell cycle and improve cytotoxic effects when given during chemotherapy , and to shorten the duration of neutropenia when administered after chemotherapy . Two hundred forty patients aged 55 to 75 years who had newly diagnosed AML were r and omly assigned to receive placebo or Escherichia coli-derived GM-CSF ( 5 micrograms/kg/d by 6-hour intravenous infusion ) starting during induction chemotherapy on day 1 and continued through and after chemotherapy until recovery of neutrophils , or evidence of regrowth of leukemia , or up to day 28 . Induction chemotherapy consisted of idarubicin ( 8 mg/m2/d on days 1 to 5 ) and cytarabine ( 100 mg/m2/d on days 1 to 7 ) . The study drug was not administered subsequent to the induction course . Patients who achieved a CR received continuous maintenance therapy for 1 year with four quarterly reinduction courses ; in the 55- to 64-year age subgroup , patients were r and omly assigned to receive or not a consolidation course before maintenance therapy . The CR rate was similar in the GM-CSF and placebo groups ( 63 % and 60.5 % , respectively ; P = .79 ) . The mortality , rate of resistant disease , and rate of regrowth of leukemia were also similar in both groups . The time to neutrophil recovery was shorter in patients who received GM-CSF ( 24 v 29 days ; P = .0001 ) , but the incidence and characteristics of infectious events were not different . The 2-year disease-free survival ( DFS ) rate was significantly improved in the GM-CSF group ( 48 % v 21 % in the placebo group ; P = .003 ) . This effect was highly significant in the cohort of patients aged 55 to 64 , but only marginal in patients > /=65 years of age . There was a trend toward a longer overall survival ( OS ) in the GM-CSF group ( P = .082 ) . In summary , the administration of GM-CSF , concomitantly with chemotherapy and thereafter during induction course in AML , shortened the time to neutrophil recovery , but did not improve the CR rate in patients aged 55 to 75 . Nonetheless , DFS and OS were significantly prolonged in patients aged 55 to 64 treated with GM-CSF . These results are promising and further evaluation of myeloid growth factors in AML is warranted BACKGROUND Intensification chemotherapy improves the prognosis for children with acute lymphoblastic leukemia ( ALL ) , but results in considerable morbidity , primarily due to myelosuppression with result ant neutropenia . Recombinant granulocyte colony-stimulating factor ( G-CSF ) shortens neutropenia following intensive chemotherapy , but potential benefits in the therapy of ALL remain inadequately explored . Accordingly , a r and omized , crossover study was undertaken to clarify this issue . PROCEDURE Seventeen children with acute lymphoblastic leukemia or T-cell non-Hodgkin lymphoma and treated on st and ard protocol s were r and omized to receive G-CSF following either the first or second intensification blocks of chemotherapy . G-CSF was administered as a single daily subcutaneous injection of 5 mcg/kg from day 9 following the start of intensification therapy , and continued until the neutrophil count exceeded 0.5 x 10(9)/l for 3 days . Study endpoints were days of neutropenia ( neutrophils < 1 x 10(9)/l ) and severe neutropenia ( neutrophils < 0.5 x 10(9)/l ) , days in hospital , days of fever , and days on antibiotics . RESULTS There were significant reductions in the duration of neutropenia ( 95 % confidence interval 3.8 - 8 days , P = 0.0001 ) , severe neutropenia ( 95 % confidence interval 1.8 - 7.4 days , P = 0.002 ) , and days in hospital ( 95 % confidence interval 0.9 - 6.3 days , P = 0.01 ) for children receiving G-CSF . Overall , the duration of neutropenia was longer following the second block ( 95 % confidence interval 2.2 - 6.4 days , P = 0.0003 ) , but this difference was abolished by G-CSF , and children , receiving G-CSF after the second intensification were more likely to restart maintenance chemotherapy on schedule ( P = 0.05 ) . CONCLUSIONS G-CSF reduces the hematological toxicity of intensification chemotherapy and may allow improved compliance with treatment scheduling PURPOSE To investigate the effect of granulocyte colony-stimulating factor ( G-CSF ) on hematopoietic toxicities , supportive care requirements , time to complete intensive therapy , and event-free survival ( EFS ) and overall survival ( OS ) in children with high-risk acute lymphoblastic leukemia ( HR-ALL ) . PATIENTS AND METHODS A total of 287 children with HR-ALL were r and omly assigned to intensive chemotherapy regimens ( New York I [ NY I ] or NY II ) as part of the Children 's Cancer Group (CCG)-1901 protocol . The induction phases consisted of five drugs ( vincristine , prednisone , l-asparaginase , daunorubicin , and cyclophosphamide ) . Initial consolidation comprised six-agent chemotherapy combined with 18 Gy of total-brain irradiation . Patients were r and omly assigned to receive G-CSF ( 5 microg/kg/day ) during either induction or initial consolidation . A crossover study analysis was done on the 259 patients who completed both phases of therapy . RESULTS The mean time to neutrophil recovery ( > /= 0.5 x 109/L ) was reduced with G-CSF ( 16.7 v 19.1 days , P = .0003 ) ; however , patients who received G-CSF did not have significantly reduced episodes of febrile neutropenia ( 149 v 164 , P = .41 ) , positive blood cultures ( 57 v 61 , P = .66 ) , or serious infections ( 75 v 79 , P = .62 ) . Hospitalization ( 14.0 v 13.9 days , P = .87 ) and induction therapy completion times ( NY I , 30.3 v 31.3 days , P = .11 ; NY II , 33.4 v 32.3 days , P = .40 ) were not significantly altered . There were no differences in 6-year EFS ( P = .24 ) or OS ( P = .54 ) between patients receiving or not receiving G-CSF on CCG-1901 , NY I and NY II . CONCLUSION Children with high-risk ALL do not appear to benefit from prophylactic G-CSF Background Infection is still a frequent cause of morbidity and mortality in acute myelogenous leukemia ( AML ) patients receiving chemotherapy . Recently the main cause of infection has changed from gram-negative to gram-positive bacteria and the resistance to antibiotics has increased . This study aim ed to access the effectiveness of antimicrobial prophylaxis ( AP ) with orally absorbable antibiotics . Methods Ninety-five AML patients receiving chemotherapy at Catholic Hemopoietic Stem Cell Transplantation Center from March 1999 to July 1999 were r and omly divided into the AP group ( 250 mg ciprofloxacin twice a day , 150 mg roxithromycin twice a day , 50 mg fluconazole once a day ) and the control group for a prospect i ve analysis . Results The incidence of fever was 82.6 % in the AP group and 91.6 % in the control group ( p = 0 . 15 ) . Though classification and sites of infections showed no difference between the two groups , the catheter associated infection occurred more frequently in the AP group in significance . The time interval between initiation of chemotherapy and onset of fever , white blood cell ( WBC ) count at the onset of fever , duration of leukopenia ( WBC < 1,000/mm3 ) , duration of systemic antibiotic therapy , mortality due to infection and hospitalization period from the data starting chemotherapy showed no differences between the two groups . Infections due to gram negative bacteria decreased to 33.3 % in the AP group ( vs. 92 % in the control group ) , but infections due to gram positive bacteria increased to 66.7 % ( vs. 8 % in the control group ) . Gram negative bacteria showed 100 % resistance to ciprofloxacin in the AP group and gram-positive bacteria showed 90–100 % resistance to erythromycin , regardless of the presence of AP . Conclusion The AP could not reduce the occurrence of infection or infection associated death in AML patients receiving chemotherapy . On considering increased gram-positive infection and resistance to fluoroquinolone and macroiide , routine prescription of AP should be reconsidered . Further studies that assess the effectiveness of AP in other malignancies , aplastic anemia and bone marrow transplantation are required Purpose To determine whether granulocyte colony-stimulating factor ( G-CSF ) administered during acute myelogenous leukemia ( AML ) induction affects hematopoietic and nonhematopoietic toxicity , length and outcome of induction therapy , event-free survival , overall survival , and prognostic significance of the day 7 bone marrow . Patients and Methods In Children 's Cancer Group study 2891 , patients were given intensively timed induction with G-CSF ( n = 254 ) after accrual for the regimen without G-CSF ( n = 258 ) was met . Results Time to neutropenic recovery after induction courses 1 and 2 was significantly shorter for patients who received G-CSF . Times to platelet recovery were similar regardless of G-CSF use . Effects on incidence of grade s 3 and 4 toxicities , infections , or fatal infections were not observed . Use of G-CSF reduced the median length of induction by 9 days and hospital stay by 6 days . Induction remission rates , overall survival , and event-free survival were similar with and without G-CSF . Day 7 bone marrow was prognostic of better long-term outcome . Patients with hypercellular day 7 marrow who received G-CSF had a higher remission rate and event-free survival than patients who did not receive G-CSF . Conclusions The incidence of severe toxic event and infection , induction remission rate , overall survival , and event-free survival were comparable regardless of G-CSF use . Use of G-CSF decreased neutropenia duration , hospital stay , and length of induction . Patients with hypercellular day 7 bone marrow who received G-CSF had an induction remission rate and event-free survival superior to those of patients who did not receive G-CSF Aerobic gram negative bacterial infections occur commonly in patients with acute leukemia undergoing intensive chemotherapy-induced bone marrow aplasia , and often arise from the gastrointestinal ( GI ) tract . The value of oral prophylactic norfloxacin ( 400 mg every 12 hours ) in preventing bacterial infections was determined for 68 adults with acute leukemia by a prospect i ve , r and omized , double-blind , placebo-controlled trial . The efficacy of norfloxacin administered prophylactically throughout the course of intensive therapy and deep ( less than 100 mm/3 ) , prolonged ( median 32 day ) granulocytopenia against infections arising from the GI tract was demonstrated by its impact on the clinical manifestations of infection , microbiologically documented gram negative bacterial infections , overall antibiotic management , and GI colonization . Although there was no difference with respect to survival , norfloxacin decreased overall morbidity associated with gram-negative infections , was well tolerated , did not impinge on systemic antibacterial or antitumor therapy , and did not predispose to the development of bacteria resistant either to itself or to multiple other antibiotics . The advantages of norfloxacin relative to other oral agents used for GI prophylaxis and the potential beneficial effects of norfloxacin or overall medical cost are discussed . Oral norfloxacin achieves the goals of GI prophylaxis by effectively suppressing early infection arising from the GI tract and inhibiting GI colonization by multiply resistant pathogens that could give rise to late-onset infections during profound chemotherapy-induced bone marrow aplasia The objective of this study was to evaluate the efficacy of oral ciprofloxacin in preventing febrile morbidity superimposed on the neutropenia induced from a paclitaxel regimen in ovarian cancer patients . Eligible patients received paclitaxel at doses of 135 to 175 mg/m2 alone or in combination with a platinum agent . They were r and omized to either an observation ( control ) group or a ciprofloxacin prophylaxis group . Patients in the ciprofloxacin group received 500 mg ciprofloxacin orally twice a day once the absolute neutrophil count ( ANC ) was less than 500/mm3 and continued until the ANC was greater than 1000/mm3 . Ninety patients were enrolled between the control ( n = 45 ) and ciprofloxacin ( n = 45 ) groups . They received 371 cycles of a paclitaxel-based regimen with 177 and 194 cycles in the control and ciprofloxacin groups , respectively . Ciprofloxacin prophylaxis was prescribed for 138 ( 71 % ) of the cycles in the ciprofloxacin group and was given for a mean duration of 7.7 days per cycle . The groups were similar in disease status and risk factors for neutropenia . Fifteen patients in the control group developed febrile neutropenia versus 12 of those in the ciprofloxacin group ( P = 0.69 ) . The mean ANC and mean length of hospital stay for neutropenic fever were also similar between groups . There was a greater frequency of an ANC < 100 associated with those prophylaxed with ciprofloxacin ( P = 0.01 ) . Only 44 % of the febrile episodes were associated with a positive culture . Staphylococcus aureus was the most frequently reported organism isolated . Considering these results , it does not appear that febrile neutropenia is reduced by ciprofloxacin during grade IV neutropenia A r and omized , double-blind , multicenter study in 181 afebrile cancer patients with ANC levels < 500/microL receiving myelosuppressive chemotherapy was undertaken to compare sargramostim ( yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor , RhuGM-CSF ) and filgrastim ( bacteria-derived recombinant human granulocyte colony-stimulating factor , RhuG-CSF ) in the treatment of chemotherapy-induced myelosuppression . Patients received daily subcutaneous ( SC ) injections of either agent until ANC levels reached at least 1500/microL. There was no statistical difference between treatment groups in the mean number of days to reach an ANC of 500/microL , but the mean number of days to reach ANC levels of 1000/microL and 1500/microL was approximately one day less in patients receiving filgrastim . Fewer patients in the sargramostim arm were hospitalized , and they had a shorter mean length of hospitalization , mean duration of fever , and mean duration of i.v . antibiotic therapy compared with patients who received filgrastim . Both growth factors were well tolerated . No patient was readmitted to the hospital after growth factor was discontinued . Sargramostim and filgrastim have comparable efficacy and tolerability in the treatment of st and ard-dose chemotherapy-induced myelosuppression in community practice BACKGROUND The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention . METHODS We r and omly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia ( < 1000 neutrophils per cubic millimeter ) was expected to occur for more than seven days to receive either oral levofloxacin ( 500 mg daily ) or placebo from the start of chemotherapy until the resolution of neutropenia . Patients were stratified according to their underlying disease ( acute leukemia vs. solid tumor or lymphoma ) . RESULTS An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis , as compared with 85 percent of those receiving placebo ( 243 of 375 vs. 308 of 363 ; relative risk , 0.76 ; absolute difference in risk , -20 percent ; 95 percent confidence interval , -26 to -14 percent ; P=0.001 ) . The levofloxacin group had a lower rate of microbiologically documented infections ( absolute difference in risk , -17 percent ; 95 percent confidence interval , -24 to -10 percent ; P<0.001 ) , bacteremias ( difference in risk , -16 percent ; 95 percent confidence interval , -22 to -9 percent ; P<0.001 ) , and single-agent gram-negative bacteremias ( difference in risk , -7 percent ; 95 percent confidence interval , -10 to -2 percent ; P<0.01 ) than did the placebo group . Mortality and tolerability were similar in the two groups . The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma . CONCLUSIONS Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia . The long-term effect of this intervention on microbial resistance in the community is not known |
12,101 | 14,584,019 | Another trial showed that cold packs decreased knee edema .
REVIEW ER 'S CONCLUSIONS Ice massage compared to control had a statistically beneficial effect on ROM , function and knee strength .
Cold packs decreased swelling .
Hot packs had no beneficial effect on edema compared with placebo or cold application .
Ice packs did not effect pain significantly compared to control in patients with OA . | BACKGROUND Osteoarthritis is a degenerative joint disease that affects mostly the weight-bearing joints in the knees and hips .
As the affected joint degenerates pain and restriction of movement often occur .
Inflammation can also occur sometimes result ing in edema of the joint with OA .
Treatment focuses on decreasing pain and improving movement .
OBJECTIVES To determine the effectiveness of thermotherapy in the treatment of OA of the knee .
The outcomes of interest were relief of pain , reduction of edema , and improvement of flexion or range of motion ( ROM ) and function . | Therapeutic trials often attempt to “ blind ” patient and investigator to the true nature of treatments received , reducing the influences of conscious or subconscious prejudices . In drug trials , this is accomplished with placebo tablets , but blinding in trials of physical treatments is more problematic . This issue arose in a clinical trial of transcutaneous electrical nerve stimulation ( TENS ) for patients with chronic low back pain . Several study design features were incorporated to promote blinding : use of sham TENS units visually identical with real units , exclusion of potential subjects with previous TENS experience , avoidance of a crossover design and use of identical visit frequency , instructions and modifications in electrode placement . Subjects were asked not to discuss treatments with the clinicians who performed outcome assessment s. Both patients and clinicians were asked to guess actual treatment assignments at the trial 's end . Every patient in the true TENS group believed the unit was functioning properly , but the degree of certainty varied . In the sham TENS group , 84 % also believed they had functioning units , but their certainty was significantly less than in the active treatment group . Differences in patient perceptions did not affect compliance , as the two groups had similar dropout rates , appointment compliance , days of TENS use and daily duration of TENS use . Clinicians guessed treatments correctly 61 % of the time ( as opposed to 50 % expected by chance ) , again suggesting partial success in blinding . These efforts at blinding may partly explain the negative trial results for TENS efficacy . We conclude that complete blinding is difficult to achieve because of sensory difference in treatment and unintended communication between patient and examiner . Nonetheless , trials of physical treatments can achieve partial blinding with the techniques described here , and the success of blinding can be assessed with simple questions at study completion The purpose of this study was to compare the effectiveness of transcutaneous nerve stimulation ( TENS ) , electroacupuncture ( EA ) , and ice massage with placebo treatment for the treatment of pain . Subjects ( n = 100 ) diagnosed with osteoarthritis ( OA ) of the knee were treated with these modalities . The parameters for evaluating the effectiveness of treatment include pain at rest , stiffness , 50 foot walking time , quadriceps muscle strength , and knee flexion degree . The results showed ( a ) that all three methods could be effective in decreasing not only pain but also the objective parameters in a short period of time ; and ( b ) that the treatment results in TENS , EA and ice massage were superior to placebo OBJECTIVE To evaluate and compare the effects of locally applied heat and cold treatments on skin and intraarticular temperature in patients with arthritis . METHODS Thirty-nine patients with arthritis of the knee were divided at r and om into 4 treatment groups ( ice chips , nitrogen cold air , ligno-paraffin , and placebo short wave ) . A temperature probe was inserted into the knee joint cavity and another placed on the overlying skin , and changes in temperature over 3 hours were recorded for each treatment group . RESULTS The mean temperature of the surface of the skin dropped from 32.2 degrees C to 16.0 degrees C after application of ice chips and from 32.6 degrees C to 9.8 degrees C after application of nitrogen cold air ; the mean intraarticular temperature decreased from 35.5 degrees C to 29.1 degrees C and from 35.8 degrees C to 32.5 degrees C , respectively , after these treatments . Treatment with ligno-paraffin increased the surface temperature by 7.5 degrees C and the temperature in the joint cavity by 1.7 degrees C. No significant changes were observed with placebo short wave diathermy . CONCLUSION The traditional model , that intraarticular temperature is decreased by superficial heat and increased by superficial cold , must be discarded . In arthritis patients , intraarticular temperature is increased by superficial heat and decreased by superficial cold . This has clear consequences for treatment policy Three rehabilitation modalities relating to in-hospital postoperative care following unilateral total knee arthroplasty ( UTKA ) were studied regarding their effect on pain management and UTKA outcome : ( 1 ) continuous passive motion ( CPM ) ; ( 2 ) CPM with transcutaneous electrical nerve stimulation ( TENS ) ; and ( 3 ) CPM with continuous cooling pad ( CCP ) . Phase I : CPM . Twenty-two UTKA patients were r and omized into two postoperative care groups : ( 1 ) 12 with CPM ; and ( 2 ) 10 with no CPM . Total hospitalization pain medication consumption was significantly less for the CPM group ( P less than .05 ) . Phase II : CPM With TENS . Forty-eight UTKA patients were r and omized into three postoperative care groups : ( 1 ) 18 with an ipsilateral thigh TENS unit delivering sensory threshold stimulation ; ( 2 ) 18 with a subthreshold TENS unit ; and ( 3 ) 12 with no TENS unit . All groups used CPM . No significant difference was found regarding pain medication consumption . Phase III : CPM With CCP . Thirty consecutive UTKA patients were divided into two postoperative care groups : ( 1 ) 15 with a CCP unit ; and ( 2 ) 15 with no CCP unit . Both groups used CPM . No significant difference was found regarding total or intramuscular hospitalization pain medication consumption . However , oral hospitalization pain medication consumption was significantly less for the CCP group ( P less than .01 ) . This postoperative UTKA study demonstrates significantly decreased total in-hospital pain medication consumption when comparing CPM vs no CPM , significantly decreased oral in-hospital pain medication consumption when comparing CPM with CCP vs CPM without CCP , but no difference when comparing CPM with TENS vs CPM without TENS . ( ABSTRACT TRUNCATED AT 250 WORDS Assessing the quality of r and omized controlled trials ( RCTs ) is important and relatively new . Quality gives us an estimate of the likelihood that the results are a valid estimate of the truth . We present an annotated bibliography of scales and checklists developed to assess quality . Twenty-five scales and nine checklists have been developed to assess quality . The checklists are most useful in providing investigators with guidelines as to what information should be included in reporting RCTs . The scales give readers a quantitative index of the likelihood that the reported methodology and results are free of bias . There are several shortcomings with these scales . Future scale development is likely to be most beneficial if questions common to all trials are assessed , if the scale is easy to use , and if it is developed with sufficient rigor The role of local heat or cold therapy used in conjunction with exercise in the rehabilitation of total knee arthroplasty patients was investigated . Thirty-six osteoarthritic patients were analyzed . Parameters evaluated were range of motion , swelling about the knee , and pain . All patients received the total condylar knee prosthesis and began range of motion rehabilitation fourteen days after operation . Results showed that temperature alteration does not augment passive range of motion after total knee arthroplasty . It was also shown that cold application decreases swelling as compared with heat . Additionally , the application of cold partially alleviates the discomfort of the rehabilitation process in certain patients |
12,102 | 28,886,596 | Our results suggest that exposure to CO is not a consistently valid surrogate measure of exposure to PM2.5 . | BACKGROUND Household air pollution from solid fuel burning is a leading contributor to disease burden globally .
Fine particulate matter ( PM2.5 ) is thought to be responsible for many of these health impacts .
A co-pollutant , carbon monoxide ( CO ) has been widely used as a surrogate measure of PM2.5 in studies of household air pollution .
OBJECTIVE The goal was to evaluate the validity of exposure to CO as a surrogate of exposure to PM2.5 in studies of household air pollution and the consistency of the PM2.5-CO relationship across different study setting s and conditions . | Diarrhoea and respiratory infections remain the biggest killers of children under 5 years in developing countries . We conducted a 5-month household r and omised controlled trial among 566 households in rural Rw and a to assess uptake , compliance and impact on environmental exposures of a combined intervention delivering high-performance water filters and improved stoves for free . Compliance was measured monthly by self-report and spot-check observations . Semi-continuous 24-h PM2.5 monitoring of the cooking area was conducted in a r and om sub sample of 121 households to assess household air pollution , while sample s of drinking water from all households were collected monthly to assess the levels of thermotolerant coliforms . Adoption was generally high , with most householders reporting the filters as their primary source of drinking water and the intervention stoves as their primary cooking stove . However , some householders continued to drink untreated water and most continued to cook on traditional stoves . The intervention was associated with a 97.5 % reduction in mean faecal indicator bacteria ( Williams means 0.5 vs. 20.2 TTC/100 mL , p<0.001 ) and a median reduction of 48 % of 24-h PM2.5 concentrations in the cooking area ( p = 0.005 ) . Further studies to increase compliance should be undertaken to better inform large-scale interventions . Trial registration : Clinical trials.gov ; NCT01882777 ; http:// clinical trials.gov/ct2/ results ? term = NCT01882777 & Search = Background Acute lower respiratory infections ( ALRI ) are a leading cause of death among children . Low birthweight is prevalent in South Asia and associated with increased risks of mortality , and morbidity , high levels of indoor household air pollution caused by open burning of biomass fuels are common and associated with high rates of ALRI and low birthweight . Alternative stove design s that burn biomass fuel more efficiently have been proposed as one method for reducing these high exposures and lowering rates of these disorders . We design ed two r and omized trials to test this hypothesis . Methods / design We conducted a pair of community-based , r and omized trials of alternative cookstove installation in a rural district in southern Nepal . Phase one was a cluster r and omized , modified step-wedge design using an alternative biomass stove with a chimney . A pre-installation period of morbidity assessment and household environmental assessment was conducted for six months in all households . This was followed by a one year step-wedge phase with 12 monthly steps for clusters of households to receive the alternative stove . The timing of alternative stove introduction was r and omized . This step-wedge phase was followed in all households by another six month follow-up phase . Eligibility criteria for phase one included household informed consent , the presence of a married woman of reproductive age ( 15–30 yrs ) or a child < 36 months . Children were followed until 36 months of age or the end of the trial . Pregnancies were identified and followed until completion or end of the trial . Phase two was an individually r and omized trial of the same alternative biomass stove versus liquid propane gas stove in a subset of households that participated in phase one . Follow-up for phase two was 12 months following stove installation . Eligibility criteria included the same components as phase one except children were only enrolled for morbidity follow-up if they were less than 24 months . The primary outcomes included : incidence of ALRI in children and birthweight . Discussion We presented the design and methods of two r and omized trials of alternative cookstoves on rates of ALRI and birthweight . Trial registration Clinical trials.gov ( NCT00786877 , Nov. 5 , 2008 ) During the first r and omized intervention trial ( RESPIRE : R and omized Exposure Study of Pollution Indoors and Respiratory Effects ) in air pollution epidemiology , we pioneered application of passive carbon monoxide ( CO ) diffusion tubes to measure long-term personal exposures to woodsmoke . Here we report on the protocol s and validations of the method , trends in personal exposure for mothers and their young children , and the efficacy of the introduced improved chimney stove in reducing personal exposures and kitchen concentrations . Passive diffusion tubes originally developed for industrial hygiene applications were deployed on a quarterly basis to measure 48-hour integrated personal carbon monoxide exposures among 515 children 0 - 18 months of age and 532 mothers aged 15 - 55 years and area sample s in a sub sample of 77 kitchens , in households r and omized into control and intervention groups . Instrument comparisons among types of passive diffusion tubes and against a continuous electrochemical CO monitor indicated that tubes responded nonlinearly to CO , and regression calibration was used to reduce this bias . Before stove introduction , the baseline arithmetic ( geometric ) mean 48-h child ( n=270 ) , mother ( n=529 ) and kitchen ( n=65 ) levels were , respectively , 3.4 ( 2.8 ) , 3.4 ( 2.8 ) and 10.2 ( 8.4 ) p.p.m . The between-group analysis of the 3355 post-baseline measurements found CO levels to be significantly lower among the intervention group during the trial period : kitchen levels : −90 % ; mothers : −61 % ; and children : −52 % in geometric means . No significant deterioration in stove effect was observed over the 18 months of surveillance . The reliability of these findings is strengthened by the large sample size made feasible by these unobtrusive and inexpensive tubes , measurement error reduction through instrument calibration , and a r and omized , longitudinal study design . These results from the first r and omized trial of improved household energy technology in a developing country and demonstrate that a simple chimney stove can substantially reduce chronic exposures to harmful indoor air pollutants among women and infants Background : Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide ( CO ) , polycyclic aromatic hydrocarbons ( PAHs ) , and particulate matter . Objective : We compared CO exposures and urinary PAH biomarkers pre- and postintervention with an improved biomass stove , the Patsari stove . Methods : In a sub sample of 63 women participating in a r and omized controlled trial in central Mexico , we measured personal CO exposure for 8 hr during the day using continuous monitors and passive sample rs . In addition , first-morning urine sample s obtained the next day were analyzed for monohydroxylated PAH metabolites by gas chromatography/isotope dilution/high-resolution mass spectrometry . Exposure data were collected during the use of an open fire ( preintervention ) and after installation of the improved stove ( postintervention ) for 47 women , enabling paired comparisons . Results : Median pre- and postintervention values were 4 and 1 ppm for continuous personal CO and 3 and 1 ppm for passive sample r CO , respectively . Postintervention measurements indicated an average reduction of 42 % for hydroxylated metabolites of naphthalene , fluorene , phenanthrene , and pyrene on a whole-weight concentration basis ( micrograms per liter of urine ) , and a 34 % reduction on a creatinine-adjusted basis ( micrograms per gram of creatinine ) . Pre- and postintervention geometric mean values for 1-hydroxypyrene were 3.2 and 2.0 μg/g creatinine , respectively . Conclusion : Use of the Patsari stove significantly reduced CO and PAH exposures in women . However , levels of many PAH biomarkers remained higher than those reported among smokers Background : A growing body of evidence indicates a relationship between household indoor air pollution from cooking fires and adverse neonatal outcomes , such as low birth weight ( LBW ) , in re source -poor countries . Objective : We examined the effect of reduced wood smoke exposure in pregnancy on LBW of Guatemalan infants in RESPIRE ( R and omized Exposure Study of Pollution Indoors and Respiratory Effects ) . Methods : Pregnant women ( n = 266 ) either received a chimney stove ( intervention ) or continued to cook over an open fire ( control ) . Between October 2002 and December 2004 we weighed 174 eligible infants ( 69 to mothers who used a chimney stove and 105 to mothers who used an open fire during pregnancy ) within 48 hr of birth . Multivariate linear regression and adjusted odds ratios ( ORs ) were used to estimate differences in birth weight and LBW ( < 2,500 g ) associated with chimney-stove versus open-fire use during pregnancy . Results : Pregnant women using chimney stoves had a 39 % reduction in mean exposure to carbon monoxide compared with those using open fires . LBW prevalence was high at 22.4 % . On average , infants born to mothers who used a stove weighed 89 g more [ 95 % confidence interval ( CI ) , –27 to 204 g ] than infants whose mothers used open fires after adjusting for maternal height , diastolic blood pressure , gravidity , and season of birth . The adjusted OR for LBW was 0.74 ( 95 % CI , 0.33–1.66 ) among infants of stove users compared with open-fire users . Average birth weight was 296 g higher ( 95 % CI , 109–482 g ) in infants born during the cold season ( after harvest ) than in other infants ; this unanticipated finding may reflect the role of maternal nutrition on birth weight in an impoverished region . Conclusions : A chimney stove reduced wood smoke exposures and was associated with reduced LBW occurrence . Although not statistically significant , the estimated effect was consistent with previous studies Background Household air pollution exposure is a major health risk , but vali date d interventions remain elusive . Methods / Design The Ghana R and omized Air Pollution and Health Study ( GRAPHS ) is a cluster-r and omized trial that evaluates the efficacy of clean fuels ( liquefied petroleum gas , or LPG ) and efficient biomass cookstoves in the Brong-Ahafo region of central Ghana . We recruit pregnant women into LPG , efficient cookstove , and control arms and track birth weight and physician-assessed severe pneumonia incidence in the first year of life . A woman is eligible to participate if she is in the first or second trimester of pregnancy and carrying a live singleton fetus , if she is the primary cook , and if she does not smoke . We hypothesize that babies born to intervention mothers will weigh more and will have fewer cases of physician-assessed severe pneumonia in the first year of life . Additionally , an extensive personal air pollution exposure monitoring effort opens the way for exposure-response analyses , which we will present alongside intention-to-treat analyses . Major funding was provided by the National Institute of Environmental Health Sciences , The Thrasher Research Fund , and the Global Alliance for Clean Cookstoves . Discussion Household air pollution exposure is a major health risk that requires well-tested interventions . GRAPHS will provide important new evidence on the efficacy of both efficient biomass cookstoves and LPG , and will thus help inform health and energy policies in developing countries . Trial registration The trial was registered with clinical trials.gov on 13 April 2011 with the identifier NCT01335490 Background Exposure to biomass fuel smoke is one of the leading risk factors for disease burden worldwide . International campaigns are currently promoting the widespread adoption of improved cookstoves in re source -limited setting s , yet little is known about the cultural and social barriers to successful improved cookstove adoption and how these barriers affect environmental exposures and health outcomes . Design We plan to conduct a one-year crossover , feasibility intervention trial in three re source -limited setting s ( Kenya , Nepal and Peru ) . We will enroll 40 to 46 female primary cooks aged 20 to 49 years in each site ( total 120 to 138 ) . Methods At baseline , we will collect information on sociodemographic characteristics and cooking practice s , and measure respiratory health and blood pressure for all participating women . An initial observational period of four months while households use their traditional , open-fire design cookstoves will take place prior to r and omization . All participants will then be r and omized to receive one of two types of improved , ventilated cookstoves with a chimney : a commercially-constructed cookstove ( Envirofit G3300/G3355 ) or a locally-constructed cookstove . After four months of observation , participants will crossover and receive the other improved cookstove design and be followed for another four months . During each of the three four-month study periods , we will collect monthly information on self-reported respiratory symptoms , cooking practice s , compliance with cookstove use ( intervention periods only ) , and measure peak expiratory flow , forced expiratory volume at 1 second , exhaled carbon monoxide and blood pressure . We will also measure pulmonary function testing in the women participants and 24-hour kitchen particulate matter and carbon monoxide levels at least once per period . Discussion Findings from this study will help us better underst and the behavioral , biological , and environmental changes that occur with a cookstove intervention . If this trial indicates that reducing indoor air pollution is feasible and effective in re source -limited setting s like Peru , Kenya and Nepal , trials and programs to modify the open burning of biomass fuels by installation of low-cost ventilated cookstoves could significantly reduce the burden of illness and death worldwide . Trial registration Clinical Trials.gov Background More than two-fifths of the world ’s population uses solid fuels , mostly biomass , for cooking . The result ing biomass smoke exposure is a major cause of chronic obstructive pulmonary disease ( COPD ) among women in developing countries . Objective To assess whether lower woodsmoke exposure from use of a stove with a chimney , compared to open fires , is associated with lower markers of airway inflammation in young women . Design We carried out a cross-sectional analysis on a sub-cohort of participants enrolled in a r and omized controlled trial in rural Guatemala , RESPIRE . Participants We recruited 45 indigenous women at the end of the 18-month trial ; 19 women who had been using the chimney stove for 18–24 months and 26 women still using open fires . Measurements We obtained spirometry and induced sputum for cell counts , gene expression of IL-8 , TNF-α , MMP-9 and 12 , and protein concentrations of IL-8 , myeloperoxidase and fibronectin . Exhaled carbon monoxide ( CO ) and 48-hr personal CO tubes were measured to assess smoke exposure . Results MMP-9 gene expression was significantly lower in women using chimney stoves . Higher exhaled CO concentrations were significantly associated with higher gene expression of IL-8 , TNF-α , and MMP-9 . Higher 48-hr personal CO concentrations were associated with higher gene expression of IL-8 , TNF- α , MMP-9 and MMP-12 ; reaching statistical significance for MMP-9 and MMP-12 . Conclusions Compared to using an open wood fire for cooking , use of a chimney stove was associated with lower gene expression of MMP-9 , a potential mediator of airway remodeling . Among all participants , indoor biomass smoke exposure was associated with higher gene expression of multiple mediators of airway inflammation and remodeling ; these mechanisms may explain some of the observed association between prolonged biomass smoke exposure and COPD We report the results of the first prospect i ve , multicenter study of acute carbon monoxide ( CO ) poisoning in pregnancy . We collected and followed cases of CO poisoning occurring during pregnancy between December 1985 and March 1989 . The sources of CO were malfunctioning furnaces ( n = 16 ) , hot water heaters ( n = 7 ) , car fumes ( n = 6 ) , and methylene chloride inhalation ( n = 3 ) . Pregnancy outcome was adversely affected in 3 of 5 pregnancies with severe toxicity ; two stillbirths , and one cerebral palsy with tomographic findings consistent with ischemic damage . All adverse outcome occurred in cases treated with high flow oxygen , whereas the 2 cases of severe toxicity with normal outcomes followed hyperbaric oxygen therapy . All 31 babies exposed in utero to mild or moderate CO poisoning exhibited normal physical and neurobehavioral development . Severe maternal CO toxicity was associated with significantly more adverse fetal cases when compared to mild maternal toxicity ( P less than 0.001 ) . It is concluded that while severe CO poisoning poses serious short- and long-term fetal risk , mild accidental exposure is likely to result in normal fetal outcome . Because fetal accumulation of CO is higher and its elimination slower than in the maternal circulation , hyperbaric oxygen may decrease fetal hypoxia and improve outcome BACKGROUND Acute respiratory infections ( ARI ) are the leading cause of the global burden of disease and have been causally linked with exposure to pollutants from domestic biomass fuels in less-developed countries . We used longitudinal health data coupled with detailed monitoring of personal exposure from more than 2 years of field measurements in rural Kenya to estimate the exposure-response relation for particulates smaller than 10 mm in diameter ( PM(10 ) ) generated from biomass combustion . METHODS 55 r and omly-selected households ( including 93 infants and children , 229 individuals between 5 and 49 years of age , and 23 aged 50 or older ) in central Kenya were followed up for more than 2 years . Longitudinal data on ARI and acute lower respiratory infections ( ALRI ) were recorded at weekly clinical examinations . Exposure to PM(10 ) was monitored by measurement of PM(10 ) emission concentration and time-activity budgets . FINDINGS With the best estimate of the exposure-response relation , we found that ARI and ALRI are increasing concave functions of average daily exposure to PM(10 ) , with the rate of increase declining for exposures above about 1000 - 2000 mg/m(3 ) . After we had included high-intensity exposure episodes , sex was no longer a significant predictor of ARI and ALRI . INTERPRETATION The benefits of reduced exposure to PM(10 ) are larger for average exposure less than about 1000 - 2000 mg/m(3 ) . Our findings have important consequences for international public-health policies , energy and combustion research , and technology transfer efforts that affect more than 2 billion people worldwide Background : Epidemiology frequently relies on surrogates of long-term exposures , often either individual-level short-term measurements or group-level based on long-term characteristics of subjects and their environment . Whereas individual-level measures are often imprecise due to within-subject variability , group-level measures tend to be inaccurate due to residual between-subject variability within groups . Rather than choose between these error-prone estimates , we borrow strength from each by use of mixed-model prediction and we compare the predictive validity . Methods : We compared alternative measures of long-term exposure to carbon monoxide ( CO ) among children in the RESPIRE woodstove r and omized control trial during years 2003 and 2004 . The main study included 1932 repeated 48-hour-average personal CO measures among 509 children from 0–18 months of age . We used a validation study with additional CO measures among a r and om sub sample of 70 of the children to compare the predictive validity of individual-level estimates ( based on observed short-term exposures ) , group-level estimates ( based on stove type and other residential characteristics ) , and mixed-model predictions that combine these 2 sources of information . Results : The estimated error variance for mixed-model prediction was 63 % lower than the individual-level measure based on the exposure data and 58 % lower than the corresponding group-level measure . Conclusions : When both individual- and group-level estimates are available but imperfect , mixed-model prediction may provide substantially better measures of long-term exposure , potentially increasing the sensitivity of epidemiologic studies to underlying causal relations The goal of this study was to assess the impact of improved stoves , house ventilation , and child location on levels of indoor air pollution and child exposure in a rural Guatemalan population reliant on wood fuel . The study was a r and om sample of 204 households with children less than 18 months in a rural village in the western highl and s of Guatemala . Socio-economic and household information was obtained by interview and observation . Twenty-four hour carbon monoxide ( CO ) was used as the primary measure of kitchen pollution and child exposure in all homes , using Gastec diffusion tubes . Twenty-four hour kitchen PM3.5 was measured in a r and om sub- sample ( n=29 ) of kitchens with co-located CO tubes . Almost 50 % of the homes still used open fires , around 30 % used chimney stoves ( planchas ) mostly from a large donor-funded programme , and the remainder of homes used various combinations including bottled gas and open fires . The 24-h kitchen CO was lowest for homes with self-purchased planchas : mean ( 95 % CI ) CO of 3.09 ppm ( 1.87–4.30 ) vs. 12.4 ppm ( 10.2–14.5 ) for open fires . The same ranking was found for child CO exposure , but with proportionately smaller differentials ( P<0.0001 ) . The 24-h kitchen PM3.5 in the sub- sample showed similar differences ( n=24 , P<0.05 ) . The predicted child PM for all 203 children ( based on a regression model from the sub- sample ) was 375 μg/m3 ( 270–480 ) for self-purchased planchas and 536 μg/m3 ( 488–584 ) for open fires . Multivariate analysis showed that stove/fuel type was the most important determinant of kitchen CO , with some effect of kitchen volume and eaves . Stove/fuel type was also the key determinant of child CO , with some effect of child position during cooking . The improved stoves in this community have been effective in reducing indoor air pollution and child exposure , although both measures were still high by international st and ards . Large donor-funded stove programmes need to aim for wider acceptance and uptake by the local families . Better stove maintenance is also required UNLABELLED Indoor air pollution ( IAP ) from domestic biomass combustion is an important health risk factor , yet direct measurements of personal IAP exposure are scarce . We measured 24-h integrated gravimetric exposure to particles < 2.5 μm in aerodynamic diameter ( particulate matter , PM₂.₅ ) in 280 adult women and 240 children in rural Yunnan , China . We also measured indoor PM₂.₅ concentrations in a r and om sample of 44 kitchens . The geometric mean winter PM₂.₅ exposure among adult women was twice that of summer exposure [ 117 μg/m³ ( 95 % CI : 107 , 128 ) vs. 55 μg/m³ ( 95 % CI : 49 , 62 ) ] . Children 's geometric mean exposure in summer was 53 μg/m³ ( 95 % CI : 46 , 61 ) . Indoor PM₂.₅ concentrations were moderately correlated with women 's personal exposure ( r=0.58 ) , but not for children . Ventilation during cooking , cookstove maintenance , and kitchen structure were significant predictors of personal PM₂.₅ exposure among women primarily cooking with biomass . These findings can be used to develop exposure assessment models for future epidemiologic research and inform interventions and policies aim ed at reducing IAP exposure . PRACTICAL IMPLICATION S Our results suggest that reducing overall PM pollution exposure in this population may be best achieved by reducing winter exposure . Behavioral interventions such as increasing ventilation during cooking or encouraging stove cleaning and maintenance may help achieve these reductions BACKGROUND Almost half the world 's population is exposed to household air pollution from biomass and coal combustion . The acute effects of household air pollution on the cardiovascular system are poorly characterized . We conducted a panel study of rural Indian women to assess whether personal exposures to black carbon during cooking were associated with acute changes in blood pressure . METHODS We enrolled 45 women ( ages 25 - 66 years ) who cooked with biomass fuels . During cooking sessions in winter and summer , we simultaneously measured their personal real-time exposure to black carbon and conducted ambulatory blood pressure measurements every 10min . We recorded ambient temperature and participants ' activities while cooking . We assessed body mass index , socioeconomic status , and salt intake . Multivariate mixed effects regression models with r and om intercepts were used to estimate the associations between blood pressure and black carbon exposure , e.g. , average exposure in the minutes preceding blood pressure measurement , and average exposure over an entire cooking session . RESULTS Women 's geometric mean ( GM ) exposure to black carbon during cooking sessions was lower in winter ( GM : 40μg/m(3 ) ; 95 % CI : 30 , 53 ) than in summer ( GM : 56μg/m(3 ) ; 95 % CI : 42 , 76 ) . Interquartile range increases in black carbon were associated with changes in systolic blood pressure from -0.4 mm Hg ( 95 % CI : -2.3 , 1.5 ) to 1.9 mm Hg ( 95 % CI : -0.8 , 4.7 ) , with associations increasing in magnitude as black carbon values were assessed over greater time periods preceding blood pressure measurement . Interquartile range increases in black carbon were associated with small decreases in diastolic blood pressure from -0.9 mm Hg ( 95 % CI : -1.7 , -0.1 ) to -0.4 mm Hg ( 95 % CI : -1.6 , 0.8 ) . Associations of a similar magnitude were estimated for cooking session-averaged values . CONCLUSIONS We found some evidence of an association between exposure to black carbon and acute increases in systolic blood pressure in Indian women cooking with biomass fuels , which may have implication s for the development of cardiovascular diseases BACKGROUND Pneumonia causes more child deaths than does any other disease . Observational studies have indicated that smoke from household solid fuel is a significant risk factor that affects about half the world 's children . We investigated whether an intervention to lower indoor wood smoke emissions would reduce pneumonia in children . METHODS We undertook a parallel r and omised controlled trial in highl and Guatemala , in a population using open indoor wood fires for cooking . We r and omly assigned 534 households with a pregnant woman or young infant to receive a woodstove with chimney ( n=269 ) or to remain as controls using open woodfires ( n=265 ) , by concealed permuted blocks of ten homes . Fieldworkers visited homes every week until children were aged 18 months to record the child 's health status . Sick children with cough and fast breathing , or signs of severe illness were referred to study physicians , masked to intervention status , for clinical examination . The primary outcome was physician-diagnosed pneumonia , without use of a chest radiograph . Analysis was by intention to treat ( ITT ) . Infant 48-h carbon monoxide measurements were used for exposure-response analysis after adjustment for covariates . This trial is registered , number IS RCT N29007941 . FINDINGS During 29,125 child-weeks of surveillance of 265 intervention and 253 control children , there were 124 physician-diagnosed pneumonia cases in intervention households and 139 in control households ( rate ratio [ RR ] 0·84 , 95 % CI 0·63 - 1·13 ; p=0·257 ) . After multiple imputation , there were 149 cases in intervention households and 180 in controls ( 0·78 , 0·59 - 1·06 , p=0·095 ; reduction 22 % , 95 % CI -6 % to 41 % ) . ITT analysis was undertaken for secondary outcomes : all and severe fieldworker-assessed pneumonia ; severe ( hypoxaemic ) physician-diagnosed pneumonia ; and radiologically confirmed , RSV-negative , and RSV-positive pneumonia , both total and severe . We recorded significant reductions in the intervention group for three severe outcomes -fieldworker-assessed , physician-diagnosed , and RSV-negative pneumonia -- but not for others . We identified no adverse effects from the intervention . The chimney stove reduced exposure by 50 % on average ( from 2·2 to 1·1 ppm carbon monoxide ) , but exposure distributions for the two groups overlapped substantially . In exposure-response analysis , a 50 % exposure reduction was significantly associated with physician-diagnosed pneumonia ( RR 0·82 , 0·70 - 0·98 ) , the greater precision result ing from less exposure misclassification compared with use of stove type alone in ITT analysis . INTERPRETATION In a population heavily exposed to wood smoke from cooking , a reduction in exposure achieved with chimney stoves did not significantly reduce physician-diagnosed pneumonia for children younger than 18 months . The significant reduction of a third in severe pneumonia , however , if confirmed , could have important implication s for reduction of child mortality . The significant exposure-response associations contribute to causal inference and suggest that stove or fuel interventions producing lower average exposures than these chimney stoves might be needed to substantially reduce pneumonia in population s heavily exposed to biomass fuel air pollution . FUNDING US National Institute of Environmental Health Sciences and WHO Abstract A cross-sectional assessment of indoor air quality in Nepal and its health effects revealed that solid biomass fuels ( animal dung , crop residue , and wood ) were the main sources of indoor air pollution affecting health . The average smoke level ( PM10 ) in kitchens using biomass fuels was about three times higher than that in those using cleaner fuels . ( kerosene , LPG , and biogas ) . Respondents in 98 r and omly selected households included 168 who cooked daily meals , of whom 94 % were disadvantaged women . Biomass smoke caused significantly more respiratory disorders than did cleaner fuels Categorized data analysis demonstrated significant associations between biomass smoke pollution and respiratory sYmptoms such as cough ; phlegm ; breathlessness ; wheezing ; and chronic respiratory diseases such as COPD and asthma . The prevalences of respiratory illnesses and symptoms were considerably higher in those living in mud and brick houses compared with concrete houses . Prevalences were also higher in those living on hills and in rural areas compared with flatl and and urban areas |
12,103 | 20,064,907 | In terms of induction therapies , MMF did not increase complete remission or partial remission rates as compared with CYC .
However , the relative risks ( RRs ) of amenorrhea and leukopenia tended to be lower in the MMF group than in the CYC group .
Meta- analysis of MMF versus AZA as a maintenance therapy showed no difference between the two groups in terms of response rates or the risk of developing end-stage renal disease .
In conclusion , MMF was found to be as effective as CYC and tended to have a better safety profile as an induction therapy for LN than CYC | The aim of this study was to assess the efficacies and toxicities of immunosuppressive treatments for lupus nephritis ( LN ) versus cyclophosphamide ( CYC ) . | The presence of renal noninflammatory necrotizing vasculopathy ( NNV ) is often associated with a severe form of lupus nephritis ( LN ) , which is unresponsive to st and ard therapy . We conducted a 6-month r and omized , prospect i ve , open-label trial comparing mycophenolate mofetil ( MMF ) ( 1.5—2.0 g/day ) with monthly i.v . cyclophosphamide ( CTX ) ( 0.75—1.0 g/m2 ) as induction therapy for class IV LN with NNV . The primary and second end points were complete remission ( CR ) and partial remission ( PR ) , respectively . Of 20 patients recruited , nine were r and omly assigned to MMF and 11 to CTX . The baseline characteristics between groups were not significant . CR was achieved in four patients ( 44.4 % ) receiving MMF and in none of the patients receiving CTX ( P = 0.026 ) . PR was achieved in two patients ( 22.2 % ) in the MMF group and three patients ( 27.2 % ) in the CTX group . The total remission rate ( CR + PR ) in the MMF and CTX group was 66.6 and 27.2 % , respectively ( P = 0.17 ) . MMF was more effective than i.v . CTX in reducing proteinuria and haematuria . Adverse events were significantly less frequent with MMF than with CTX ( P = 0.028 ) . MMF was superior to i.v . CTX in inducing CR of LN with NNV and had a more favourable safety profile . Lupus ( 2007 ) 16 , 707—712 For the treatment of proliferative lupus nephritis , long-term cyclophosphamide ( CY ) regimens are efficacious , however , at the expense of substantial toxicity . In the last decade , sequential regimens of short-term CY induction followed by either mycophenolate mofetil ( MMF ) or azathioprine ( AZA ) maintenance have shown to be efficacious and safe reducing the long-term exposure to CY . In a maintenance study including predominantly Hispanics and African-Americans , the patients who received MMF and AZA maintenance had a higher cumulative probability of remaining free of the composite of death or chronic renal failure ( CRF ) compared to quarterly intravenous CY ( IVCY ) maintenance ( 89 % in MMF , 80 % , in AZA and 45 % in IVCY ) . Likewise , MMF and AZA maintenance were associated with significantly lower incidence of severe infections ( 2 % in each MMF or AZA , and 25 % in IVCY ) , sustained amenorrhea ( 6 % in MMF , 8 % in AZA , and 32 % in IVCY ) , and hospitalizations ( one hospital-days per patient-year in each MMF or AZA , and 10 in IVCY ) . In a European induction study including predominantly Caucasians , patients who received any of two sequential regimens , low dose versus high dose IVCY induction both followed by AZA maintenance , had a high cumulative probability of remaining free of treatment failure ( 84 % in low dose IVCY and 80 % in high dose IVCY ; treatment failure defined as a composite of free of corticosteroid resistant flare , nephrotic syndrome , doubling creatinine , and persistent elevated creatinine ) . Low dose IVCY and high dose IVCY induction were associated with low incidence of sustained amenorrhea ( 4 % in each group ) and severe infections ( 11 % in low dose and 22 % in high dose IVCY induction ) . Of interest , most of the severe infection episodes occurred while patients were receiving IVCY induction . Finally an Asian study demonstrated that patients with proliferative lupus nephritis could be effectively treated with short-term oral CY induction followed by AZA maintenance . The cumulative probability of complete remission was 76 % . The relapse rate was only 11 % . The incidence of permanent amenorrhea and infection were 8 % and 33 % , respectively . None of the Asian patients had an increase in serum creatinine level to double the baseline value . Maintenance therapies with MMF or AZA following short-term CY induction in a sequential regimen are efficacious and safe for the treatment of high-risk patients with proliferative lupus nephritis Recent studies have suggested that mycophenolate mofetil ( MMF ) may offer advantages over intravenous cyclophosphamide ( IVC ) for the treatment of lupus nephritis , but these therapies have not been compared in an international r and omized , controlled trial . Here , we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational , two-phase ( induction and maintenance ) study . We r and omly assigned 370 patients with classes III through V lupus nephritis to open-label MMF ( target dosage 3 g/d ) or IVC ( 0.5 to 1.0 g/m(2 ) in monthly pulses ) in a 24-wk induction study . Both groups received prednisone , tapered from a maximum starting dosage of 60 mg/d . The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine . Secondary end points included complete renal remission , systemic disease activity and damage , and safety . Overall , we did not detect a significantly different response rate between the two groups : 104 ( 56.2 % ) of 185 patients responded to MMF compared with 98 ( 53.0 % ) of 185 to IVC . Secondary end points were also similar between treatment groups . There were nine deaths in the MMF group and five in the IVC group . We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events , serious adverse events , or infections . Although most patients in both treatment groups experienced clinical improvement , the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis Patients with lupus membranous nephropathy ( LMN ) are at substantial long-term risk for morbidity and mortality associated with protracted nephrotic syndrome , including ESRD . The optimal treatment for this condition is controversial . Forty-two patients with LMN participated in a r and omized , controlled trial to compare adjunctive immunosuppressive drugs with prednisone alone . Adjunctive regimens included either cyclosporine ( CsA ) for 11 mo or alternate-month intravenous pulse cyclophosphamide ( IVCY ) for six doses ; the control group received alternate-day prednisone alone . Median proteinuria was 5.4 g/d ( range 2.7 to 15.4 g/d ) . We assessed the primary outcome , time to remission of proteinuria during the 12-mo protocol , by univariate survival analysis . At 1 yr , the cumulative probability of remission was 27 % with prednisone , 60 % with IVCY , and 83 % with CsA. Although both IVCY and CsA were more effective than prednisone in inducing remissions of proteinuria , relapse of nephrotic syndrome occurred significantly more often after completion of CsA than after IVCY . By multivariate survival analysis , treatment with prednisone and high- grade proteinuria ( > 5 g/d ) but not race or ethnicity were independently associated with a decreased probability of remission . Adverse effects during the 12-mo protocol included insulin-requiring diabetes ( one with prednisone and two with CsA ) , pneumonia ( one with prednisone and two with CsA ) , and localized herpes zoster ( two with IVCY ) . In conclusion , regimens containing CsA or IVCY are each more effective than prednisone alone in inducing remission of proteinuria among patients with LMN OBJECTIVE To compare the efficacy and side effects of intermittent pulse cyclophosphamide plus methylprednisolone with continuous oral cyclophosphamide plus prednisolone , followed by azathioprine , in patients with proliferative glomerulonephritis caused by systemic lupus erythematosus ( SLE ) . METHODS A multicentre r and omised controlled trial was conducted between June 1992 and May 1996 involving eight European centres . All patients satisfied the American College of Rheumatology criteria for SLE and had biopsy proven proliferative lupus nephritis . All received corticosteroids in addition to cytotoxic drugs , as defined in the protocol , for two years . The trial was terminated after four years as recruitment was disappointing . RESULTS 32 SLE patients with lupus nephritis were recruited : 16 were r and omised to intermittent pulse cyclophosphamide and 16 to continuous cyclophosphamide plus azathioprine . Mean duration of follow up was 3.7 years in the continuous group ( range 0 to 5.6 ) and 3.3 years in the pulse group ( range 0.25 to 6 ) . Three patients were excluded from the pulse therapy group as they were later found to have pure mesangial glomerulonephritis . Two patients in the continuous therapy group developed end stage renal failure requiring dialysis , but none in the intermittent pulse therapy ( p = 0.488 ; NS ) . There were similar numbers of side effects and withdrawals from treatment in both groups . There were three deaths : two in the intermittent pulse therapy group and one in the continuous therapy group . CONCLUSIONS There was no statistically significant difference in efficacy and side effects between the two regimens . Infectious complications occurred commonly , so careful monitoring is required during treatment BACKGROUND The aim of the present study was to evaluate the efficacy of mycophenolate mofetil in the induction therapy of proliferative lupus nephritis . METHODS Forty-four patients from eight centres with newly diagnosed lupus nephritis World Health Organization class III or IV were r and omly assigned to either mycophenolate mofetil ( MMF ) 2 g/day for 6 months or intravenous cyclophosphamide ( IVC ) 0.75 - 1 g/m(2 ) monthly for 6 months in addition to corticosteroids . RESULTS Remission occurred in 13 out of 25 patients ( 52 % ) in the IVC group and 11 out of 19 patients ( 58 % ) in the MMF group ( P = 0.70 ) . There were 12 % in the IVC group and 26 % in the MMF group that achieved complete remission ( P = 0.22 ) . Improvements in haemoglobin , the erythrocyte sedimentation rate , serum albumin , serum complement , proteinuria , urinary activity , renal function and the Systemic Lupus Erythematosus Disease Activity Index score were similar in both groups . Twenty-four follow-up renal biopsies at the end of therapy showed a significant reduction in the activity score in both groups . The chronicity index increased in both groups but was only significant in the IVC group . Adverse events were similar . Major infections occurred in three patients in each group . There was no difference in gastrointestinal side-effects . CONCLUSIONS MMF in combination with corticosteroids is an effective induction therapy for moderately severe proliferative lupus nephritis OBJECTIVE In the Euro-Lupus Nephritis Trial ( ELNT ) , 90 patients with lupus nephritis were r and omly assigned to a high-dose intravenous cyclophosphamide ( IV CYC ) regimen ( 6 monthly pulses and 2 quarterly pulses with escalating doses ) or a low-dose IV CYC regimen ( 6 pulses of 500 mg given at intervals of 2 weeks ) , each of which was followed by azathioprine ( AZA ) . After a median followup of 41 months , a difference in efficacy between the 2 regimens was not observed . The present analysis was undertaken to extend the followup and to identify prognostic factors . METHODS Renal function was prospect ively assessed quarterly in all 90 patients except 5 who were lost to followup . Survival curves were derived using the Kaplan-Meier method . RESULTS After a median followup of 73 months , there was no significant difference in the cumulative probability of end-stage renal disease or doubling of the serum creatinine level in patients who received the low-dose IV CYC regimen versus those who received the high-dose regimen . At long-term followup , 18 patients ( 8 receiving low-dose and 10 receiving high-dose treatment ) had developed permanent renal impairment and were classified as having poor long-term renal outcome . We demonstrated by multivariate analysis that early response to therapy at 6 months ( defined as a decrease in serum creatinine level and proteinuria < 1 g/24 hours ) was the best predictor of good long-term renal outcome . CONCLUSION Long-term followup of patients from the ELNT confirms that , in lupus nephritis , a remission-inducing regimen of low-dose IV CYC followed by AZA achieves clinical results comparable with those obtained with a high-dose regimen . Early response to therapy is predictive of good long-term renal outcome OBJECTIVE Glomerulonephritis is a severe manifestation of systemic lupus erythematosus ( SLE ) that is usually treated with an extended course of intravenous ( IV ) cyclophosphamide ( CYC ) . Given the side effects of this regimen , we evaluated the efficacy and the toxicity of a course of low-dose IV CYC prescribed as a remission-inducing treatment , followed by azathioprine ( AZA ) as a remission-maintaining treatment . METHODS In this multicenter , prospect i ve clinical trial ( the Euro-Lupus Nephritis Trial [ ELNT ] ) , we r and omly assigned 90 SLE patients with proliferative glomerulonephritis to a high-dose IV CYC regimen ( 6 monthly pulses and 2 quarterly pulses ; doses increased according to the white blood cell count nadir ) or a low-dose IV CYC regimen ( 6 fortnightly pulses at a fixed dose of 500 mg ) , each of which was followed by AZA . Intent-to-treat analyses were performed . RESULTS Followup continued for a median of 41.3 months in the low-dose group and 41 months in the high-dose group . Sixteen percent of those in the low-dose group and 20 % of those in the high-dose group experienced treatment failure ( not statistically significant by Kaplan-Meier analysis ) . Levels of serum creatinine , albumin , C3 , 24-hour urinary protein , and the disease activity scores significantly improved in both groups during the first year of followup . Renal remission was achieved in 71 % of the low-dose group and 54 % of the high-dose group ( not statistically significant ) . Renal flares were noted in 27 % of the low-dose group and 29 % of the high-dose group . Although episodes of severe infection were more than twice as frequent in the high-dose group , the difference was not statistically significant . CONCLUSION The data from the ELNT indicate that in European SLE patients with proliferative lupus nephritis , a remission-inducing regimen of low-dose IV CYC ( cumulative dose 3 gm ) followed by AZA achieves clinical results comparable to those obtained with a high-dose regimen Mycophenolate mofetil ( MMF ) and the sequential use of cyclophosphamide followed by azathioprine ( CTX-AZA ) demonstrate similar short-term efficacy in the treatment of diffuse proliferative lupus nephritis ( DPLN ) , but MMF is associated with less drug toxicity . Results from an extended long-term study , with median follow-up of 63 mo , that investigated the role of MMF as continuous induction-maintenance treatment for DPLN are presented . Thirty-three patients were r and omized to receive MMF , and 31 were r and omized to the CTX-AZA treatment arm , both in combination with prednisolone . More than 90 % in each group responded favorably ( complete or partial remission ) to induction treatment . Serum creatinine in both groups remained stable and comparable over time . Creatinine clearance increased significantly in the MMF group , but the between-group difference was insignificant . Improvements in serology and proteinuria were comparable between the two groups . A total of 6.3 % in the MMF group and 10.0 % of CTX-AZA-treated patients showed doubling of baseline creatinine during follow-up ( P = 0.667 ) . Both the relapse-free survival and the hazard ratio for relapse were similar between MMF- and CTX-AZA-treated patients ( 11 and nine patients relapsed , respectively ) and between those with MMF treatment for 12 or > /=24 mo . MMF treatment was associated with fewer infections and infections that required hospitalization ( P = 0.013 and 0.014 , respectively ) . Four patients in the CTX-AZA group but none in the MMF group reached the composite end point of end-stage renal failure or death ( P = 0.062 by survival analysis ) . It is concluded that MMF and prednisolone constitute an effective continuous induction-maintenance treatment for DPLN in Chinese patients Cyclophosphamide ( CYC ) has proven beneficial in preserving renal function in patients with lupus with diffuse proliferative glomerulonephritis ( DPGN ) . However , the optimal route of CYC administration is unknown because direct comparative studies are unavailable . In this open study , we compared the renal outcome of two historical cohorts of patients with diffuse proliferative lupus nephritis ( World Health Organization classes IVa and IVb ) treated with either intravenous ( IV ) pulse CYC ( group A ; n = 22 ) or sequential oral CYC followed by azathioprine ( AZA ; group B ; n = 21 ) and followed up prospect ively . Both groups of patients had similar clinical , biochemical , and renal parameters at baseline . At 24 months posttreatment , significant improvements in proteinuria , creatinine clearance , serum albumin level , and lupus serological results were evident in both groups . Compared with patients in group A , patients in group B had more complete or partial remission ( 90 % versus 73 % ) and less risk for treatment failure ( 5 % versus 14 % ) , renal flares ( 5 % versus 14 % ) , and doubling of creatinine levels ( 5 % versus 9 % ) , but the difference was not statistically significant . However , patients treated with oral immunosuppression had an insignificant increase in rates of herpes zoster infection ( 19 % versus 9 % ) and menstrual disturbance ( 50 % versus 29 % ) . We conclude that sequential oral immunosuppression with CYC and AZA tended to have better efficacy than IV pulse CYC in the treatment of lupus DPGN but was associated with more toxicities . Additional r and omized trials involving a larger cohort of patients with a longer period of observation are necessary OBJECTIVE To make an open label prospect i ve trial for comparing the therapeutic effects of mycophenolate mofetil ( MMF ) vs cyclophosphamide ( CYC ) pulse therapy on patients with diffuse proliferative lupus nephritis ( DPLN ) . METHODS Forty-six patients with biopsy proven active DPLN were enrolled in this study . Twenty-three patients were given MMF orally at a dosage of 1.0 - 1.5 g/d ( MMF Group ) . Another 23 cases received conventional intermittent CYC pulse therapy ( CYC Group ) . Supplemental steroid treatment was offered in the same manner to both groups . The age , sex distribution and severity of renal damage were matched in two groups . Therapeutic effects were evaluated at the end of six-month treatment . Fifteen patients in the MMF Group and 12 patients in the CYC Group had repeated renal biopsy at that time . RESULTS MMF therapy was more effective in reducing proteinuria and hematuria . A 50 % reduction of urinary protein and urinary red blood cell excretion from baseline value in 69.6 % and 91.3 % patients in the MMF Group , while only 47.8 % and 65.2 % in the CYC Group . MMF was more effective in inhibiting autoantibody production ( especially anti-dsDNA antibody ) and in decreasing serum cryoglobulin levels . Pathologically , the MMF group showed more markedly reduction in glomerular immune deposits with less glomerular necrosis , and less microthrombi , less crescent formation and vascular changes in the repeated renal biopsy as compared with the CYC group . Adverse reactions related to the treatment included gastrointestinal symptoms 26.1 % and 43.5 % in the MMF and CYC Groups respectively , infection 17.4 % in the MMF group and 30.4 % in the CYC group . CONCLUSION MMF was more effective in controlling the clinical activity of DPLN and renal vascular lesions as compared with CYC pulse therapy in a 6 month follow-up study We evaluated renal function in 107 patients with active lupus nephritis who participated in long-term r and omized therapeutic trials ( median follow-up , seven years ) . For patients taking oral prednisone alone , the probability of renal failure began to increase substantially after five years of observation . Renal function was better preserved in patients who received various cytotoxic-drug therapies , but the difference was statistically significant only for intravenous cyclophosphamide plus low-dose prednisone as compared with high-dose prednisone alone ( P = 0.027 ) . The advantage of treatment with intravenous cyclophosphamide over oral prednisone alone was particularly apparent in the high-risk subgroup of patients who had chronic histologic changes on renal biopsy at study entry . Patients treated with intravenous cyclophosphamide have not experienced hemorrhagic cystitis , cancer , or a disproportionate number of major infections . We conclude that , as compared with high-dose oral prednisone alone , treatment of lupus glomerulonephritis with intravenous cyclophosphamide reduces the risk of end-stage renal failure with few serious complications Introduction Lupus nephritis ( LN ) is a severe manifestation of systemic lupus erythematosus ( SLE ) that is usually treated with an extended course of intravenous ( IV ) cyclophosphamide ( CYC ) . Given the side effects of this regimen , we evaluated the short-term efficacy and toxicity of a course of low-dose remission-inducing IV CYC followed by azathioprine ( AZA ) in a prospect i ve controlled study among Egyptian patients with severe LN . Patients and methods In this single center , prospect i ve clinical trial , we assigned 46 SLE patients with diffuse proliferative glomerulonephritis to either a high-dose ( a maximum of 1 g/dose ) of IV CYC ( HD-CYC ) for six monthly pulses followed by two quarterly pulses or a fixed low-dose ( 500 mg/dose ) of IV CYC ( LD-CYC ) for six fortnightly pulses with a cumulative dose of 3 g. Each regimen was followed by AZA.The objective To compare between efficacy , potential toxicity and outcome of parenteral LD-CYC versus HD-CYC therapy for severe LN . Results Twenty patients ( 2 male and 18 female ) received fortnightly fixed LD-CYC while 26 ( 5 male and 21 female ) received monthly HD-CYC therapy . At the end of the study ( 1 year after starting therapy ) , there was no difference either in patients ’ or in renal survival in both groups . Significant improvement of disease activity ( SLE disease activity index ) as well as rise of serum albumin was noticed with both regimens . Renal relapse was observed in 11.5 % of HD-CYC patients and in none of the LD-CYC therapy patients . Treatment failure was seen in 5 % and 3.4 % ( P = NS ) of LD-CYC and HD-CYC patients , respectively . Infection ( pneumonia and cellulitis ) occurred in five patients in the LD-CYC group and four patients of HD-CYC ; again this difference was not statistically significant . Conclusion A remission-inducing regimen of LD-CYC ( cumulative dose 3 g ) followed by AZA for SLE patients with proliferative LN achieves clinical results comparable to those obtained with HD-CYC without serious infection in both regimens Until recently , intravenous cyclophosphamide pulses with oral corticosteroids were regarded st and ard therapy for proliferative lupus nephritis ( LN ) . Azathioprine , a less toxic alternative , was never proven to be inferior . In the first Dutch lupus nephritis study ( enrollment between 1995 and 2001 ) , we r and omized 87 proliferative LN patients to either cyclophosphamide pulses ( 750 mg/m(2 ) , 13 pulses in 2 years ) combined with oral prednisone ( CY ) or to azathioprine ( 2 mg/kg/day in 2 years ) combined with intravenous pulses of methylprednisolone ( 3 x 3 pulses of 1000 mg ) and oral prednisone ( AZA ) . After a median follow-up of 5.7 years ( interquartile range 4.1 - 7.2 years ) , doubling of serum creatinine was more frequent in the AZA group , although not statistically significant ( relative risk ( RR ) : 4.1 , with 95 % confidence interval ( 95 % CI ) : 0.8 - 20.4 ) . Relapses occurred more often in the AZA group ( RR : 8.8 , 95 % CI : 1.5 - 31.8 ) . Creatinine and proteinuria at last visit did not differ between the two treatment arms . Moreover , 88.4 % of the patients in the AZA arm were still free of cyclophosphamide treatment . During the first 2 years , the frequency of remission was not different , but infections , especially herpes zoster virus infections ( HZV ) were more frequent in the AZA group . Parameters for ovarian function did not differ between the two groups . In conclusion , in this open-label r and omized controlled trial , cyclophosphamide was superior to azathioprine with regard to renal relapses and HZV . At last follow-up , there were no differences in serum creatinine or proteinuria between the two groups . However , since our study lacked sufficient power , longer follow-up is needed to reveal putative differences |
12,104 | 23,979,926 | Very low quality evidence determined that pulsed electromagnetic field therapy ( PEMF ) and repetitive magnetic stimulation ( rMS ) were more effective than placebo , while transcutaneous electrical nerve stimulation ( TENS ) showed inconsistent results .Very low quality evidence determined that PEMF , rMS and TENS were more effective than placebo .
We can not make any definite statements on the efficacy and clinical usefulness of electrotherapy modalities for neck pain .
Current evidence for PEMF , rMS , and TENS shows that these modalities might be more effective than placebo .
Galvanic current , iontophoresis , EMS , and a static magnetic field did not reduce pain or disability . | BACKGROUND Neck pain is common , disabling and costly .
The effectiveness of electrotherapy as a physiotherapeutic option remains unclear .
This is an up date of a Cochrane review first published in 2005 and previously up date d in 2009 .
OBJECTIVES This systematic review assessed the short , intermediate and long-term effects of electrotherapy on pain , function , disability , patient satisfaction , global perceived effect , and quality of life in adults with neck pain with and without radiculopathy or cervicogenic headache . | BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review Study Design . A question naire was mailed to 3000 r and omly selected 35‐45‐year‐old individuals in three communities in central Sweden . Objectives . To study the 1‐year prevalence of spinal pain and its ramifications in the form of pain , function , sick leave , and health care use . Summary of Background Data . Previous research ers have used a variety of definitions and population s , but primarily have investigated the occurrence of pain . Comprehensive data are needed concerning health care use , the degree of the pain problem , functional disturbances , and sick leave . Method . Participants in the study completed a question naire regarding spinal pain during the past year including the degree of their experienced pain , functional impairment , lost work days , and health care use . Results . A total of 2305 people ( 78.5 % ) responded to the question naire . Nonrespondents had similar characteristics but a slightly lower 1‐year prevalence rate than did respondents . For respondents , the prevalence of spinal pain during the past year was 66.3 % , with women having a slightly higher prevalence than men . Approximately 25 % of the respondents indicated that they had a substantial problem based on ratings of pain , functional impairment , and sick leave . Work absenteeism reported to the Public Social Insurance Office involved 19 % of those with pain , but an additional 15 % indicated unreported absenteeism . On average , those with pain visited health care providers three times during the past year , but a small number of those who experienced pain consumed large amounts of health care and illness benefits . An important gender difference was shown , such that when pain was at its worst , men took sick leave , whereas women sought health care . Conclusions . Taken together , these data indicate that spinal pain is common among 35‐45‐year‐old men and ‐ women , and that it is related to marked problems for approximately one fourth of those who experience pain . Gender differences exist in the pattern of sick leave and health care use , and a small proportion of those with pain consume very large amounts of the re sources . Consequently , there is a need for early , effective , preventive treatments Background Current evidence on electrotherapies for the management of chronic neck pain is either lacking or conflicting . New therapeutic devices being introduced to the market should be investigated for their effectiveness and efficacy . The ENAR ® ( Electro Neuro Adaptive Regulator ) therapy device combines Western biofeedback with Eastern energy medicine . Methods A small , preliminary r and omised and controlled single-blinded trial was conducted on 24 participants ( ten males , 14 females ) between the ages of 18 to 50 years ( median age of 40.5 ) Consent was obtained and participants were r and omly allocated to one of three groups – ENAR , Transcutaneous Electrical Nerve Stimulation ( TENS ) , or control therapy – to test the hypothesis that ENAR therapy would result in superior pain reduction/disability and improvements in neck function compared with TENS or control intervention . The treatment regimen included twelve 15-minute treatment sessions over a six week period , followed by two assessment periods . Visual Analogue Scale ( VAS ) pain scores , Neck Disability Index ( NDI ) scores , Patient Specific Functional Scale ( PSFS ) scores and Short Form 36v1 ( SF-36 ) quality of life scores reported by participants were collected at each of the assessment s points throughout the trial ( 0 , 6 , 12 , 18 and 24 weeks ) . Results Eligible participants ( n = 30 ) were recruited and attended clinic visits for 6 months from the time of r and omisation . Final trial sample ( n = 24 ) comprised 9 within the ENAR group , 7 within the TENS group and 8 within the control group . With an overall study power of 0.92 , the ENAR group showed a decrease in mean pain score from measurement at time zero ( 5.0 ± 0.79 95%CI ) to the first follow-up measurement at six weeks ( 1.4 ± 0.83 95%CI ) . Improvement was maintained until week 24 ( 1.75 ± 0.9 95%CI ) . The TENS and control groups showed consistent pain levels throughout the trial ( 3.4 ± 0.96 95%CI and 4.1 ± 0.9 95%CI respectively ) . Wald analysis for pain intensity was significant for the ENAR group ( p = 0.01 ) . Six month NDI scores showed the disability level of the ENAR group ( 11.3 ± 4.5 95%CI ) was approximately half that of either the TENS ( 22.9 ± 4.8 95%CI ) or the control ( 29.4 ± 4.5 95%CI ) groups . NDI analysis using the Wald method , indicated significant reductions in disability only for the ENAR group ( p = 0.022 ) . PSFS results also demonstrated significantly better performance of ENAR ( p = 0.001 ) compared to both alternative interventions . Differential means analysis of the SF-36 results favoured ENAR for all of the subscales . Six of the initial 30 participants discontinued the trial protocol . Conclusion ENAR therapy participants reported a significant reduction in the intensity of neck pain ( VAS ) and disability ( NDI ) , as well as a significant increased function ( PSFS ) and overall quality of life ( SF-36 ) than TENS or control intervention participants . Due to the modest sample size and restricted cohort characteristics , future larger and more comprehensive trials are required to better evaluate the potential efficacy of the ENAR device in a more widely distributed sample population .Trial Registration This study has been registered with the Australian Clinical Trials Registry ( ACTR ) : ACTRN012606000438550 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 Successful treatment of torticollis with electromyographic ( EMG ) biofeedback has been reported in a number of single case and single group studies . The present investigation represents the first controlled outcome study . Twelve torticollis patients were r and omly assigned to EMG biofeedback or relaxation training and grade d neck exercises ( RGP ) . The procedure involved three sessions of baseline assessment , 15 sessions of EMG BF or RGP , 6 sessions of EMG BF or RGP plus home-management , 6 sessions of home-management alone , and follow-up 3 months after the end of treatment . A variety of outcome measures were used including physiological ( EMG from the two sternocleidomastoid muscles , skin conductance level ) , behavioral ( angle of head deviation , range of movement of the head ) , and self-report ( depression , functional disability , body concept ) , therapist and “ significant other ” reports and independent observer assessment of videos . In both groups , neck muscle activity was reduced from pre- to posttreatment . This reduction was greater in the EMG biofeedback group . There was evidence of feedback-specific neck muscle relaxation in the EMG biofeedback group . Therefore , the outcome was not due to nonspecific factors and could be attributed to feedback-specific effects . Changes in skin conductance level showed that neck muscle relaxation was not simply mediated by a general reduction of “ arousal . ” Significant improvements of extent of head deviation , and range of movement of the head , as well as reductions of depression were present , which were not different in the two groups . At the end of treatment , no patient was asymptomatic . Any therapeutic benefit was generally maintained at follow-up . The results and the procedural simplicity of RGP make the issue of cost-efficacy of EMG biofeedback a pertinent one . Further controlled outcome studies of EMG biofeedback treatment of torticollis with larger sample s are required Abstract The aim of this study was to evaluate the short , medium and long – term effects of peripheral repetitive magnetic stimulation ( rMS ) on myofascial pain compared with transcutaneous electrical nerve stimulation (TENS).Fifty – three subjects with myofascial trigger points ( TPs ) at the level of the superior trapezius muscle were allocated r and omly to three groups . The first group ( n = 17 ) was treated with rMS , the second ( n = 18 ) with TENS and the third ( n = 18 ) received a placebo treatment . Each treatment consisted of ten daily 20–minute sessions . Patients were evaluated before and immediately following treatment , and at one and three months after the end of treatment . Outcome measures were : the “ neck pain and disability visual analogue scale ” ( NPDVAS ) , an algometric evaluation of pain , an evaluation of the TP characteristics , and the range of cervical bending and rotation contralateral to the affected trapezius muscle . At the end of treatment , the rMS group showed a significant improvement in the NPDVAS , algometry , TP characteristics , and cervical contralateral rotation . This improvement also persisted at one and three months post – therapy . After treatment , the TENS group showed significant improvement in the same outcome measures except for algometry . At the one month follow – up visit , this improvement had returned to non significant levels in all outcome measures with the exception of NPDVAS.No significant effect of TENS was seen at the three – month follow – up visit . The placebo group showed no significant improvement in any measure . Our results strongly suggest that at medium and longer term intervals peripheral rMS may be more effective than TENS for the treatment of myofascial pain This study investigated effectiveness of manual therapy ( MT ) with transcutaneous electrical nerve stimulation ( TENS ) to reduce pain intensity in patients with mechanical neck disorder ( MND ) . A r and omized multi-centered controlled clinical trial was performed in 12 Primary Care Physiotherapy Units in Madrid Region . Ninety patients were included with diagnoses of subacute or chronic MND without neurological damage , 47 patients received MT and 43 TENS . The primary outcome was pain intensity measured in millimeters using the Visual Analogue Scale ( VAS ) . Also disability , quality of life , adverse effects and sociodemographic and prognosis variables were measured . Three evaluations were performed ( before , when the procedure finished and six months after ) . Seventy-one patients ( 79 % ) completed the follow-up measurement at six months . In more than half of the treated patients the procedure had a clinical ly relevant " short term " result after having ended the intervention , when either MT or TENS was used . The success rate decreased to one-third of the patients 6 months after the intervention . No differences can be found in the reduction of pain , in the decrease of disability nor in the quality of life between both therapies . Both analyzed physiotherapy techniques produce a short-term pain reduction that is clinical ly relevant OBJECTIVES To compare the efficacy of combined transcutaneous acupoint electrical stimulation ( TAES ) and electromagnetic millimeter wave ( EMMW ) therapy as an add-on treatment for pain relief and physical functional activity enhancement among adults with sub-acute non-specific spinal pain in either the low back or neck . DESIGN A non-blinded study with data obtained before , immediate , one week and three months after intervention . SETTING The Telehealth Clinic and Community Centre , Hong Kong . PARTICIPANTS Forty-seven subjects with either sub-acute neck or low back pain . INTERVENTION Subjects were r and omly allocated to either an intervention group ( n=23 ) or a control group ( n=24 ) . These groups were then divided into subgroups according to the site of their spinal pain-neck or back . The intervention group had eight treatments over a three-week period of TAES and EMMW . OUTCOME MEASURES Changes from baseline to the end of treatment were assessed at intervals of one week and three months on either neck or low back pain intensity [ by Visual Analogue Scale ( VAS ) ] ; stiffness level ; stress level ; neck or low back lateral flexion and forward flexion in cm , and interference with daily activities . RESULTS The baseline VAS scores for the intervention and control groups were 5.34 and 5.18 out of 10 , respectively ( P value=0.77 ) . At the one week and three month assessment s , there were no significant differences between the groups-VAS ( P value=0.09 and 0.27 , respectively ) . A further subgroup of chronic pain sufferers ( n=31 ) was identified and these had significantly reduced pain intensity at the one week assessment ( P value=0.04 ) but this was not sustained at post three months after treatment ( P value=0.15 ) . Improvements in stiffness level , stress level , and functional disability level in the intervention group were not significant . CONCLUSIONS Our study shows that there was a reduction in pain intensity , stress and stiffness level immediately after the eight sessions of treatment ( TAES and EMMW ) , though the effect is not sustained after a week . No pain relief was found with the neck pain subgroup . However , the reduction in subjective average pain intensity among the chronic pain subgroup was sustained at the post one week assessment for the intervention group but not at the post three month assessment OBJECTIVE To examine the efficacy of transcranial electrical stimulation a non-invasive method of reducing pain . DESIGN A r and omized , double-blind , placebo-controlled trial . SUBJECTS A total of 119 patients with chronic pain . METHODS Patients were treated with either transcranial electrical stimulation or an active placebo device . Short- and long-term follow-ups were evaluated for treatment efficacy with 4 ordinal scale variables : visual analogue scale ( pain level ) , SLEEP ( how often does pain disturb sleep ) , FREQ ( frequency of pain ) and MED ( frequency of use of medications to relieve pain ) . RESULTS Pain level decreased significantly in the transcranial electrical stimulation-treated group compared with the active-placebo group 3 weeks after the end of treatment ( p = 0.0017 between groups ) . Other parameters did not demonstrate significant differences . Three months after the end of treatment this effect was maintained and other treatment parameters showed similar improvements . CONCLUSION Transcranial electrical stimulation is an effective non-invasive method for pain relief . The active placebo device has a powerful effect on reported pain , which diminishes in the long-term . The involvement of possible neural mechanisms is discussed OBJECTIVE To assess the antalgic activity of thermomagnetic b and ages and belts in cervical and lumbar pain syndrome ( respectively CPS and LPS ) , compared with non-magnetic devices ( placebo ) . PATIENTS AND METHODS It was a double-blind study on two groups of 30 patients suffering from chronic back pain ( 15 cervical and 15 lumbar in each group ) . Patients had to stop any previous analgesic or antiinflammatory drug treatment at least 8 days prior to entering the study . Each subject included in the study had to wear the b and age/belt for 8 hours a day for 14 consecutive days . Before the start , every subject underwent an initial assessment of his/her current pain level and functional status through the use of two visual analogue scales ( pain and functional status ) and one verbal scale ( pain ) . After the end of the study , a final assessment was made using the same tools . RESULTS 93 and 97 % ( respectively in the CPS and LPS group ) were the percentages of patients in the actively-treated arm who showed an improvement both in pain level and in functional status . This improvement was statistically significant vs. the correspondent placebo-treated groups ( respectively , 20 and 23 % in the CPS and in the LPS ) . No adverse events associated to treatment were signalled . CONCLUSIONS The use of thermomagnetic b and ages and belts ( which are , virtually in all cases , free of contraindications ) allows us a more rational and easy management of the patient suffering from chronic back pain & NA ; Chronic neck pain is highly prevalent . To determine the efficacy and safety of acupuncture , in comparison with transcutaneous nerve stimulation‐placebo ( TENS‐placebo ) in the treatment of chronic uncomplicated neck pain , a single blind prospect i ve study was design ed , to be carried out at a Primary Healthcare Centre , with r and om assignment to two parallel groups and with evaluation and analysis by independent evaluators . A r and om assignment was made from 123 patients of the 149 initially recruited . These patients had been diagnosed with uncomplicated neck pain and experienced neck motion‐related pain intensity equal to or exceeding 30 on a visual analogue scale ( VAS ) from 0 to 100 mm . The treatment with acupuncture was compared with TENS‐placebo , applied over 5 sessions in three weeks . The primary endpoint was the change in maximum pain intensity related to motion of the neck , one week after the final treatment . Sensitivity was analysed per protocol ( PP ) and variant analyses were by intention to treat ( ITT ) . Adjustment was made for confounders by multiple linear regression , including baseline values and rescue therapy . By ITT analysis , the change in the pain‐VAS variable was greater among the experimental group ( 28.1 ( 95 % CI 21.4–34.7 ) ) . The improvements in quality of life ( physical aspect ) , active neck mobility and reduced rescue medication were clinical ly and statistically significant . In the treatment of the intensity of chronic neck pain , acupuncture is more effective than the placebo treatment and presents a safety profile making it suitable for routine use in clinical practice OBJECTIVE To compare the effects of manipulation treatment and transcutaneous electrical nerve stimulation ( TENS ) on patients with cervicogenic headache . METHODS Seventy patients with cervicogenic headache were r and omly allocated to receive manipulation treatment and TENS treatment , which were given every other day respectively for total 40 days . The headache degree ( numeric rating scale , NRS ) , frequency , lasting time and the range of motion ( ROM ) of the cervical spine 2 weeks before treatment and 4 weeks after treatment , were compared . RESULTS Before treatment , there were no significant differences in the headache NRS scores , frequency , lasting time and the ROM scores between the two groups ( P>0.05 ) . After treatment , the headache NRS score , frequency , lasting time in the manipulation group decreased significantly ( P<0.01 ) , while in the TENS group just the headache NRS score decreased significantly ( P<0.05 ) . The ROM scores in both groups showed no significant changes ( P>0.05 ) . The response rate of manipulation treatment is 94.5 % , significantly higher than 64.5 % of TENS treatment ( P<0.05 ) . CONCLUSION The manipulation treatment is an effective method for patients with cervicogenic headache AIM Myofascial pain syndrome ( MPS ) is a frequent cause of chronic muscoloskeletal pain . Transcutaneous electrical nerve stimulation ( TENS ) is one of the most frequently employed treatments in MPS . The aim of this study is to compare the short and medium-term effects of frequency modulated neural stimulation ( FREMS ) to those of TENS in MPS . METHODS Forty subjects with upper trapezius MPS were r and omly allocated to 1 of 2 groups , treated with either FREMS ( n=19 ) or TENS ( n=21 ) . Each treatment consisted in 10 sessions lasting 20 min each . Patients were evaluated before treatment , at 1 week , and at 1 and 3 months after the end of treatment . Clinical evaluation included parameters for measurement of pain levels using the neck pain and disability visual analogue scale ( NPDVAS ) and algometry , evaluation of myofascial trigger point characteristics and measurement of the range of cervical movement ( range of motion , ROM ) . RESULTS The FREMS group showed a significant improvement in the NPDVAS , algometry , in myofascial trigger point characteristics , and in the ROM ( homolateral rotation , controlateral rotation , bending and extension ) after the end of treatment and at 1 and 3 months follow-up evaluation . The TENS group showed significant improvement in the same outcome measures except for algometry and cervical extension , but these improvements were maintained only at the 1 month follow-up evaluation . However , were not observed statistically significant differences between FREMS of TENS in many of outcome measures . CONCLUSIONS Both FREMS and TENS have positive short-term effects on MPS . But , medium-term effects were achieved only with FREMS The purpose of this study was to evaluate the effect of electromagnetic field therapy ( PEMF ) on pain , range of motion ( ROM ) and functional status in patients with cervical osteoarthritis ( COA ) . Thirty-four patients with COA were included in a r and omized , double-blind study . PEMF was administrated to the whole body using a mat 1.8 × 0.6 m in size . During the treatment , the patients lay on the mat for 30 min per session , twice a day for 3 weeks . Pain levels in the PEMF group decreased significantly after therapy ( p<0.001 ) , but no change was observed in the placebo group . The active ROM , paravertebral muscle spasm and neck pain and disability scale ( NPDS ) scores improved significantly after PEMF therapy ( p<0.001 ) but no change was observed in the sham group . The results of this study are promising , in that PEMF treatment may offer a potential therapeutic adjunct to current COA therapies in the future OBJECTIVE To determine the efficacy of neck stabilization exercises in the management of neck pain . PATIENTS AND METHODS Sixty patients with neck pain were r and omized to 3 groups , as follows : group 1 - -physical therapy agents including transcutaneous electrical nerve stimulation , continuous ultrasound and infra-red irradiation ; group 2 - -physical therapy agents + isometric and stretching exercises ; and group 3 - -physical therapy agents + neck stabilization exercises . The exercises were performed as a home training programme following a 3-week supervised group exercise . The patients were evaluated with a visual analogue scale , by intake of paracetamol , Neck Disability Index , Beck Depression Scale and range of motion in the 3 planes at baseline and at months 1 , 3 , 6 , 9 and 12 . RESULTS Compared with baseline , all groups showed a significant decrease in visual analogue scale scores during the first 6 months . However , this improvement was maintained only in group 3 at 9 and 12 months , with a significant difference among the groups ( p<0.05 ) . During the study , the improvement in disability was marked in group 3 with respect to Neck Disability Index , Beck Depression Scale and range of motion in the frontal plane ( p<0.05 ) . CONCLUSION This study demonstrates the superiority of the neck stabilization exercises , with some advantages in the pain and disability outcomes , compared with isometric and stretching exercises in combination with physical therapy agents for the management of neck pain CURRENT magnetic coil stimulators can efficiently activate neural structures without deep electrode placement and the local discomfort associated with transcutaneous electrical stimulation used in pain control . We tested the possibility of reducing pain in patients with localized musculoskeletal processes by applying repetitive magnetic stimulation on the tender body region . Thirty patients were r and omized to receive 40 min of real or sham magnetic stimulation . After a single session , real magnetic stimulation significantly exceeded the sham effect : a 101-point pain score decreased by 59 % in the treated group and 14 % in sham-treated patients ( z = −3.26 , p = 0.001 ) . The pain relief attained regularly persisted for several days . Results indicate that powerful magnetic coil stimulation can efficiently reduce pain originating from localized musculoskeletal injuries Thirty patients with acute cervical pain were r and omized into 3 groups and treated with neck collar , transcutaneous nerve stimulation , or manual therapy . The improvement was rapid in all groups , but the restoration of the cervical mobility was significantly more rapid in the transcutaneous nerve stimulation group . Some of the patients with manual therapy treatment had remarkably quick symptom reduction , although this was not significantly better than the collar alone . It is concluded that transcutaneous nerve stimulation is a valuable pain reducer and gives a more rapid restoration of cervical mobility in acute cervical pain 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 OBJECTIVE The purpose of this study was to investigate the immediate effect of electric point stimulation in treating latent upper trapezius trigger points compared to placebo . DESIGN Double blind r and omised placebo-controlled trial . SETTING Anglo-European College of Chiropractic . PARTICIPANTS Sixty participants with latent upper trapezius trigger points . INTERVENTIONS Electric point stimulator type of TENS , or detuned ( inactive ) electric point stimulator type of TENS . MAIN OUTCOME MEASURES The three outcome measures were pressure pain threshold at the trigger point , a numerical rating scale for pain elicited over the trigger point , and lateral cervical flexion to the side opposite the trigger point . RESULTS On the outcome of pressure pain threshold the electric point stimulator group had a mean change of 0.49 ( 0.99 ) kg/cm(2 ) , while the placebo group had a mean change of 0.45 ( 0.98 ) kg/cm(2 ) ( t = 0.16 , df = 58 , p = 0.88 ) . For change in pain over the trigger point , the electric point stimulator group had a mean decrease of 0.93 ( 0.87 ) points , while the placebo group had a mean decrease of 0.23 ( 0.97 ) points ( t = 0.70 , df = 58 , p = 0.005 ) . On the outcome of change in lateral cervical flexion the electric point stimulator group had a mean increase of 2.87 ( 4.55 ) degrees , while the placebo group had a mean increase of 1.99 ( 2.49 ) degrees ( t = 0.92 , df = 58 , p = 0.36 ) . CONCLUSION Electric point stimulator type of TENS is superior to placebo only in reduction of pain for treating latent upper trapezius trigger points Back pain and the whiplash syndrome are very common diseases involving tremendous costs and extensive medical effort . A quick and effective reduction of symptoms , especially pain , is required . In two prospect i ve r and omized studies , patients with either lumbar radiculopathy in the segments L5/S1 or the whiplash syndrome were investigated . Inclusion criteria were as follows : either clinical ly verified painful lumbar radiculopathy in the segments L5/S1 and a Laségue 's sign of 30 degrees ( or more ) , or typical signs of the whiplash syndrome such as painful restriction of rotation and flexion/extension . Exclusion criteria were prolapsed intervertebral discs , systemic neurological diseases , epilepsy , and pregnancy . A total of 100 patients with lumbar radiculopathy and 92 with the whiplash syndrome were selected and entered in the study following a 1:1 ratio . Both groups ( magnetic field treatment and controls ) received st and ard medication consisting of diclofenac and tizanidine , while the magnetic field was only applied in group 1 , twice a day , for a period of two weeks . In patients suffering from radiculopathy , the average time until pain relief and painless walking was 8.2 + /- 0.5 days in the magnetic field group , and 11.7 + /- 0.5 days in controls p < 0.04 ) . In patients with the whiplash syndrome , pain was measured on a ten-point scale . Pain in the head was on average 4.6 before and 2.1 after treatment in those receiving magnetic field treatment , and 4.2/3.5 in controls . Neck pain was on average 6.3/1.9 as opposed to 5.3/4.6 , and pain in the shoulder/arm was 2.4/0.8 as opposed to 2.8/2.2 ( p < 0.03 for all regions ) . Hence , magnetic fields appear to have a considerable and statistically significant potential for reducing pain in cases of lumbar radiculopathy and the whiplash syndrome Thirty patients suffering from painful syndromes of the spine were admitted to a r and omized controlled clinical trial . They were divided into two groups and treated either with transcutaneous electrical nerve stimulation ( TENS ) , one application every other day , for 20 days or with TENS and an ointment containing etofenamate 10 % gel , 3 - 5 cm daily on the day of TENS therapy , and the same dose twice daily on the other days . The associated therapy achieved , when compared with TENS alone , a statistically significant better outcome . Furthermore a marked improvement of symptoms was observed in a shorter period of time . Therapy was well tolerated and in only four cases mild , self-limiting , skin reactions were observed . On the basis of these results the use of etofenamate and TENS could represent a viable alternative to systemic nonsteroidal antiinflammatory drug therapy PURPOSE To describe and explore the relationships between pain , emotional state and coping strategies in patients with chronic radicular neck pain before and after surgery or conservative treatments . METHODS We r and omize 81 conseutive patients with cervical radicular pain and nerve root compression , verified by MRI , to either surgical decompression with fusion or physiotherapy or neck collar . Emotional state was both measured with Mood Adjective Check List . Hospital Anxiety and Depression Scale and with a Coping Strategies Question naire . Pain was measured with VAS and function with Disability Index Rating . Measurements were made before treatment , and follow ups after 3 and 12 months post treatment . RESULTS We found generally a low emotional state with anxiety , depression and sleep-disturbances not only connected to pain . Pain improved faster in the surgery group but after one year no differences were seen . Surgery and physiotherapy improved function with heavy work compared to collar after 3 months . Many patients used active coping before treatment , but after treatment more passive coping strategies were found . CONCLUSION We recommend a multidisciplinary rehabilitation with cognitive behavioural therapy and psychological interventions OBJECTIVES This study compared the relative effectiveness of cervical spine manipulation and mobilization for neck pain . METHODS Neck-pain patients were r and omized to the following conditions : manipulation with or without heat , manipulation with or without electrical muscle stimulation , mobilization with or without heat , and mobilization with or without electrical muscle stimulation . RESULTS Of 960 eligible patients , 336 enrolled in the study . Mean reductions in pain and disability were similar in the manipulation and mobilization groups through 6 months . CONCLUSIONS Cervical spine manipulation and mobilization yield comparable clinical outcomes This prospect i ve , r and omised study compares the efficacy of surgery , physiotherapy and cervical collar with respect to pain , motor weakness and sensory loss in 81 patients with long-lasting cervical radiculopathy corresponding to a nerve root that was significantly compressed by spondylotic encroachment , with or without an additional bulging disk , as verified by MRI or CT-myelography . Pain intensity was registered on a visual analogue scale ( VAS ) , muscle strength was measured by a h and -held dynamometer , Vigorometer and pinchometer . Sensory loss and paraesthesia were recorded . The measurements were performed before treatment ( control 1 ) , 4 months after the start of treatment ( control 2 ) and after a further 12 months ( control 3 ) . A healthy control group was used for comparison and to test the reliability of the muscle-strength measurements . The study found that before start of treatment the groups were uniform with respect to pain , motor weakness and sensory loss . At control 2 the surgery group reported less pain , less sensory loss and had better muscle strength , measured as the ratio of the affected side to the non-affected side , compared to the two conservative treatment groups . After a further year ( control 3 ) , there were no differences in pain intensity , sensory loss or paraesthesia between the groups . An improvement in muscle strengths , measured as the ratio of the affected to the non-affected side , was seen in the surgery group compared to the physiotherapy group in wrist extension , elbow extension , shoulder abduction and internal rotation , but there were no differences in the ratios between the collar group and the other treatment groups . With respect to absolute muscle strength of the affected sides , there were no differences at control 1 . At control 2 , the surgery group performed somewhat better than the two other groups but at control 3 there were no differences between the groups . We conclude that pain intensity , muscle weakness and sensory loss can be expected to improve within a few months after surgery , while slow improvement with conservative treatments and recurrent symptoms in the surgery group make the 1-year results about equal The st and ard treatment of acute whiplash injuries ( soft collar and analgesia ) is frequently unsuccessful . Pulsed electromagnetic therapy PEMT ( as pulsed 27 MHz ) has been shown to have pro-healing and anti-inflammatory effects . This study examines the effect of PEMT on the acute whiplash syndrome . One half of the 40 patients entering the study received active PEMT collars : the other half facsimile ( placebo ) . All patients were given instructions to wear the collar for eight hours a day at home and advised to mobilise their necks . At 2 and 4 weeks the actively treated group had significantly improved ( p less than 0.05 ) in terms of pain ( visual analogue scale ) . By chance movement scores for the PEMT group were significantly worse at entry to the study than the control group ( p less than 0.05 ) . At 12 weeks they had become significantly better ( p less than 0.05 ) . PEMT as described is safe for domiciliary use and this study suggests that PEMT has a beneficial effect in the management of the acute whiplash injury OBJECTIVE To evaluate short- and medium-term effects of peripheral repetitive magnetic stimulation ( rMS ) on myofascial pain . METHODS Eighteen patients who presented with myofascial trigger points ( TPs ) at the level of the superior trapezius were separated into two groups according to a restricted r and omization scheme . Group 1 ( n=9 ) underwent treatment with rMS that consisted of a total of 10 sessions , each lasting 20min , in which 4000 magnetic stimuli were administered in 5s trains at 20Hz at the TP . Group 2 ( n=9 ) received a placebo treatment that consisted of the application of a non-functioning ultrasound therapy device to the TP . Patients were evaluated before treatment , at the end of treatment , and again 1 week and 1 month after the conclusion of the treatment . Clinical evaluation included parameters for measuring pain levels ( VAS , NPDVAS and algometry ) , the myofascial TP characteristics and the range of cervical movement ( ROM ) . RESULTS The rMS group showed a significant improvement in VAS , NPDVAS , algometry , as well as in the characteristics of the TP after conclusion of treatment . Improvements in the ROM were also present in rotation and controlateral bending . This improvement persisted after 1 month . On the other h and , the placebo group did not show any significant improvement in the tests considered . CONCLUSIONS The results of this study show that peripheral rMS may have positive short- and medium-term therapeutic effects on myofascial pain OBJECTIVE To describe the satisfaction and expectations of the patients with neck pain with relation to the physical therapy received and to analyse the relationship between the patient 's characteristics and his degree of satisfaction and expectation . DESIGN This study is performed in the setting of a r and om clinical trial . PARTICIPANTS Subjects between 18 and 60 years of age with subacute mechanical neck disorders . MAIN VARIABLES Patient 's expectations and satisfaction with the received treatment ( scale similar to Likert 's Scale ) . OTHER VARIABLES : Pain intensity , episodes of previous neck pain , depression and anxiety symptoms ( Goldberg Scale ) , age and gender , physical disability , general state of health , duration of the present episode of neck pain , regular exercise and regular consumption of medicines . RESULTS AND CONCLUSIONS A total of 90 patients were studied . The mean age was 40.1 years and 88.9 % were female . Thirteen per cent of the subjects expected partial relief , 60 % expected good recovery and 27 % expected complete recovery . Those patients who have not suffered previous episodes of neck pain and those who have a higher score on the Goldberg Scale have a higher expectation of recovering after the treatment . About patients ' satisfaction after the intervention , 2 % totally unsatisfied , 1 % very unsatisfied , 2 % somewhat unsatisfied , 2 % indifferent , 17 % somewhat satisfied , 42 % very satisfied and 30 % totally satisfied . Those patients who experienced a greater decrease in pain were more satisfied . It would be interesting to study in depth the measurement of patients ' satisfaction with the received physical therapy and to extend it to other pathologies 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 . A r and omized trial was conducted in which patients with back and neck pain , visiting a general practitioner , were allocated to chiropractic or physiotherapy . Objectives . To compare outcome and costs of chiropractic and physiotherapy as primary treatment for patients with back and neck pain , with special reference to subgroups , recurrence rate , and additional health care use at follow‐up evaluation 12 months after treatment . Summary of Background Data . Earlier studies on the effect of spinal manipulation have shown inconsistent results . Mostly they include only short‐term follow‐up periods , and few cost‐effectiveness analyses have been made . Methods . A group of 323 patients aged 18‐60 years who had no contraindications to manipulation and who had not been treated within the previous month were included . Outcome measures were changes in Oswestry scores , pain intensity , and general health ; recurrence rate ; and direct and indirect costs . Results . No differences were detected in health improvement , costs , or recurrence rate between the two groups . According to Oswestry score , chiropractic was more favorable for patients with a current pain episode of less than 1 week ( 5 % ) and physiotherapy for patients with a current pain episode of greater than 1 month ( 6.8 % ) . Nearly 60 % of the patients reported two or more recurrences . More patients in the chiropractic group ( 59 % ) than in the physiotherapy group ( 41 % ) sought additional health care . Costs varied considerably among individuals and subgroups ; the direct costs were lower for physiotherapy in a few subgroups . Conclusions . Effectiveness and costs of chiropractic or physiotherapy as primary treatment were similar for the total population , but some differences were seen according to subgroups . Back problems often recurred , and additional health care was common . Implication s of the result are that treatment policy and clinical decision models must consider subgroups and that the problem often is recurrent . Models must be implemented and tested Study Design . This prospect i ve , r and omized study compares the efficacy of surgical and conservative treatments in patients with long-lasting cervical radicular pain . Objectives . To compare the effects of surgery , physiotherapy , and a cervical collar . Summary of Background Data . There are no previous controlled outcome studies that have compared surgical treatment with nonsurgical treatment of patients with cervical radicular pain . Methods . The study group comprised 81 patients with cervicobrachial pain of at least 3 months ' duration , in whom the distribution of the arm pain corresponded to a nerve root that was significantly compressed by spondylotic encroachment with or without an additional bulging disc , as verified by magnetic resonance imaging or computed tomographic myelography . The patients were r and omly allocated to surgery ( Cloward technique ) , individually adapted physiotherapy , or a cervical collar . The therapeutic effects were evaluated with respect to pain intensity by the visual analogue scale , function by the Sickness Impact Profile , and mood by the Mood Adjective Check List . The measurements were performed before treatment ( control 1 ) , shortly after treatment ( control 2 ) , and after a further 12 months ( control 3 ) . Results . At control 1 , the groups were uniform . At control 2 , the surgery group reported less pain ( visual analogue scale ) and , like the physiotherapy group , better function ( Sickness Impact Profile ) than the collar group . At control 3 , there was no difference in visual analogue scale , Sickness Impact Profile , and Mood Adjective Check List measurements among the groups . Conclusions . In the treatment of patients with long-lasting cervical radicular pain , it appears that a cervical collar , physiotherapy , or surgery are equally effective in the long term This study is design ed to investigate the immediate effectiveness of electrotherapy on myofascial trigger points of upper trapezius muscle . Sixty patients ( 25 males and 35 females ) who had myofascial trigger points in one side of the upper trapezius muscles were studied . The involved upper trapezius muscles were treated with three different methods according to a r and om assignment : group A muscles ( n = 18 ) were given placebo treatment ( control group ) ; group B muscles ( n = 20 ) were treated with electrical nerve stimulation ( ENS ) therapy ; and group C muscles ( n = 22 ) were given electrical muscle stimulation ( EMS ) therapy . The effectiveness of treatment was assessed by conducting three measurements on each muscle before and immediately after treatment : subjective pain intensity [ ( PI ) with a visual analog scale ] , pressure pain threshold [ ( PT ) with algometry ] , and range of motion [ ( ROM ) with a goniometer ] of upper trapezius muscle ( lateral bending of cervical spine to the opposite side ) . When the effectiveness of treatment was compared with that of the placebo group ( group A ) , there was significant improvement in PI and PT in group B ( P < 0.01 ) but not in group C ( P > 0.05 ) . The improvement of ROM was significantly more in group C ( P < 0.01 ) as compared with that in group A or group B. When each group was divided into two additional subgroups based on the initial PI , it was found that ENS could reduce PI and increase PT significantly ( P < 0.05 ) , but did not significantly ( P > 0.05 ) improve ROM , as compared with the placebo group for both subgroups . EMS could significantly ( P < 0.05 ) improve ROM , but not PT , better than the placebo groups , for either subgroup . It could reduce PI significantly more ( P < 0.05 ) than placebo controls only for the subgroup with mild to moderate pain , but not with severe pain . For pain relief , ENS was significantly better ( P < 0.05 ) than EMS ; but for the improvement of ROM , EMS was significantly better ( P < 0.05 ) than ENS . It is concluded that ENS is more effective for immediate relief of myofascial trigger point pain than EMS , and EMS has a better effect on immediate release of muscle tightness than ENS One-half of the students taking part in a double-blind study received a microamperage electrical stimulation of trigger points in the neck and shoulder region with the Electro-Acuscope 80 . All the subjects were evaluated by digital palpatory physical examination for the presence of trigger points before each of their treatments . Results indicate that the subjects who received treatment had a higher change of trigger-point indicators compared to those receiving the placebo treatment . A two-tailed t-test indicated significant results ( P less than 0.001 ) . It appears that microamperage electrical stimulation is effective in the treatment of trigger points Gabis L , Shklar B , Geva D : Immediate influence of transcranial electrostimulation on pain and & bgr;-endorphin blood levels : An active placebo-controlled study . Am J Phys Med Rehabil 2003;82:81–85 . Background Stimulation of the antinociceptive system by noninvasive electrical current from electrodes placed on the head is a renewed method of pain relief . Methods We conducted a r and omized , double-blind , placebo-controlled study on 20 chronic back pain patients . They were treated with either transcranial electrostimulation ( TCES ) or an active placebo device . Pain level and serum & bgr;-endorphin levels were measured before and after treatment . Results & bgr;-Endorphin level increased in seven of the ten patients from the treatment group and did not change in eight of ten patients from control group ( P = 0.057 between groups ) . Pain level decreased in eight treated patients and seven control patients ( significant decrease for each group , no significant difference between groups ) . Conclusions Transcranial electrostimulation is a nonpharmacologic method of pain relief accompanied or mediated by & bgr;-endorphin release . The comparable degree of the initial clinical response emphasizes the powerful placebo effect on reported pain not mediated by endorphin release . This preliminary study shows that noninvasive electrical stimulation is a safe treatment with a positive effect on & bgr;-endorphin blood levels Our aim was to examine the effects of a seated thoracic spine distraction thrust manipulation included in an electrotherapy/thermal program on pain , disability , and cervical range of motion in patients with acute neck pain . This r and omized controlled trial included 45 patients ( 20 males , 25 females ) between 23 and 44 years of age presenting with acute neck pain . Patients were r and omly divided into 2 groups : an experimental group which received a thoracic manipulation , and a control group which did not receive the manipulative procedure . Both groups received an electrotherapy program consisting of 6 sessions of TENS ( frequency 100Hz ; 20min ) , superficial thermo-therapy ( 15min ) and soft tissue massage . The experimental group also received a thoracic manipulation once a week for 3 consecutive weeks . Outcome measures included neck pain ( numerical pain rate scale ; NPRS ) , level of disability ( Northwick Park Neck Pain Question naire ; NPQ ) and neck mobility . These outcomes were assessed at baseline and 1 week after discharge . A 2-way repeated- measures ANOVA with group as between-subject variable and time as within-subject variable was used . Patients receiving thoracic manipulation experienced greater reductions in both neck pain , with between-group difference of 2.3 ( 95 % CI 2 - 2.7 ) points on a 11-NPRS , and perceived disability with between-group differences 8.5 ( 95 % CI 7.2 - 9.8 ) points . Further , patients receiving thoracic manipulation experienced greater increases in all cervical motions with between-group differences of 10.6 degrees ( 95 % CI 8.8 - 12.5 degrees ) for flexion ; 9.9 degrees ( 95 % CI 8.1 - 11.7 degrees ) for extension ; 9.5 degrees ( 95 % CI 7.6 - 11.4 degrees ) for right lateral-flexion ; 8 degrees ( 95 % CI 6.2 - 9.8 degrees ) for left lateral-flexion ; 9.6 degrees ( 95 % CI 7.7 - 11.6 degrees ) for right rotation ; and 8.4 degrees ( 95 % CI 6.5 - 10.3 degrees ) for left rotation . We found that the inclusion of a thoracic manipulation into an electrotherapy/thermal program was effective in reducing neck pain and disability , and in increasing active cervical mobility in patients with acute neck pain OBJECTIVE To investigate the immediate effect of physical therapeutic modalities on myofascial pain in the upper trapezius muscle . DESIGN R and omized controlled trial . SETTING Institutional practice . PATIENTS One hundred nineteen subjects with palpably active myofascial trigger points ( MTrPs ) . INTERVENTION Stage 1 evaluated the immediate effect of ischemic compression , including 2 treatment pressures ( P1 , pain threshold ; P2 , averaged pain threshold and tolerance ) and 3 duration s ( T1 , 30s ; T2 , 60s ; T3 , 90s ) . Stage 2 evaluated 6 therapeutics combinations , including groups B1 ( hot pack plus active range of motion [ ROM ] ) , B2 ( B1 plus ischemic compression ) , B3 ( B2 plus transcutaneous electric nerve stimulation [ TENS ] ) , B4 ( B1 plus stretch with spray ) , B5 ( B4 plus TENS ) , and B6 ( B1 plus interferential current and myofascial release ) . MAIN OUTCOME MEASURES The indexes of changes in pain threshold ( IThC ) , pain tolerance ( IToC ) , visual analog scale ( IVC ) , and ROM ( IRC ) were evaluated for treatment effect . RESULTS In stage 1 , the IThC , IToC , IVC , and IRC were significantly improved in the groups P1T3 , P2T2 , and P2T3 compared with the P1T1 and P1T2 treatments ( P<.05 ) . In stage 2 , groups B3 , B5 , and B6 showed significant improvement in IThC , ItoC , and IVC compared with the B1 group ; groups B4 , B5 , and B6 showed significant improvement in IRC compared with group B1 ( P<.05 ) . CONCLUSIONS Ischemic compression therapy provides alternative treatments using either low pressure ( pain threshold ) and a long duration ( 90s ) or high pressure ( the average of pain threshold and pain tolerance ) and short duration ( 30s ) for immediate pain relief and MTrP sensitivity suppression . Results suggest that therapeutic combinations such as hot pack plus active ROM and stretch with spray , hot pack plus active ROM and stretch with spray as well as TENS , and hot pack plus active ROM and interferential current as well as myofascial release technique , are most effective for easing MTrP pain and increasing cervical ROM BACKGROUND Many patients with chronic whiplash-associated disorders have reduced neuromuscular control of the neck and head . It has been proposed that a new sling exercise therapy may promote neuromuscular control of the neck . OBJECTIVES To compare the effects of traditional physiotherapy vs traditional physiotherapy combined with a new sling exercise therapy on discomfort and function in patients with chronic whiplash-associated disorders who have unsettled compensation cl aims ; and to investigate possible additional effects of guided , long-term home training . DESIGN A r and omized multi-centre trial with 4 parallel groups . METHODS A total of 214 patients were assigned r and omly to 4 treatment groups , and received either traditional physiotherapy with or without home training , or new sling exercise therapy with or without home training . Outcome measures were pain , disability , psychological distress , sick leave and physical tests . RESULTS A total of 171 patients ( 80 % ) completed the study . There were no important statistical or clinical differences between the groups after 4 months of treatment . There was a small statistically significant effect at 12-month follow-up in both groups with home training regarding pain during rest ( p = 0.05 ) and reported fatigue in the final week ( p = 0.02 ) . CONCLUSION No statistically significant differences were found between the traditional physiotherapy group and the new sling exercise group , with or without home training . Since the groups were not compared with a control group without treatment , we can not conclude that the studied treatments are effective for patients with whiplash-associated disorder , only that they did not differ in our study Abstract The present paper describes the effect of high frequency , low frequency and placebo TENS on acute oro‐facial pain in 62 patients , attending to an emergency clinic for dental surgery ; they had all suffered pain for 1–4 days . The patients were r and omly assigned to one of three groups receiving either high frequency ( 100 Hz ) , low frequency ( 2 Hz ) or placebo TENS . In the two groups receiving TENS ( 42 patients ) 16 patients reported a reduction in pain intensity exceeding 50 % ; out of these 16 patients , 4 patients reported complete relief of pain . In the placebo group ( 20 patients ) 2 patients reported a pain reduction of more than 50 % ; out of these 2 patients , none reported a complete pain relief . Mechanical vibratory stimulation augmented the pain reduction obtained by TENS in 5 out of 10 patients UNLABELLED We report the results of a cost-effectiveness evaluation of pulsed electromagnetic field ( PEMF ) therapy and spa therapy ( ST ) versus usual care ( control ) for chronic neck pain . MATERIAL S AND METHODS Inclusion criteria were age 18 to 80 years with pain in the neck area of more than 3 months ' duration and no contraindications for PEMF therapy and ST . R and omization to the ST ( n=25 ) and PEMF groups ( n=26 ) was blinded , as was collection of data . Non-included subjects ( n=29 ) underwent usual care . The trial respected the Helsinki declaration , and informed consent was obtained from subjects . The analysis was intent to treat ; the main outcome measure was increase in health dimension scores on the MOS SF-36 in terms of increase in French health care costs from 6 months preceding to 6 months after the start of the study . RESULTS The increase in health care costs was less for the PEMF group ( + 68 euro+/-539 [ 95 % confidence interval ( CI ) ] : -145.0 + 281 ) than the ST and control groups . The increase tended to be less , but not significantly , for the ST group ( + 373+/-938 euro [ 95 % CI , -14.0 + 76.0 ] ) than for controls ( + 618+/-2715 euro [ 95 % CI , -434.0 + 167.0 ] ) . The gain of one physical MOS SF-36 unit during one year cost 3400 euro [ 95 % CI , -6759 + 13 100 ] for the PEMF group , 29,000 euro [ 95 % CI , -1093 + 59 375 ] for the ST group and 95076 euro [ 95 % CI , -66 769 + 256 923 ] for the control group , but the differences were not significant . COMMENTARY These results suggest a potential cost-effectiveness for ST and particularly PEMF as compared to usual care in chronic cervical pain . Our results perhaps lack significance probably because of lack of statistical power and do not distinguish costs related or not to chronic cervical pain In order to assess the long-term efficacy of a multi-modal rehabilitation approach on whiplash injury , 60 patients were recruited within two months after neck injury . They were r and omly allocated either to an experimental multimodal treatment ( A ) consisting of postural training , manual technique and psychological support or to a control treatment ( B ) , using physical agents only , such as electrical and sonic modalities . Pain level , range of movement , self-rating scale of treatment efficacy and return-to-work delay were evaluated before and at the end of treatment , and later , 30 and 180 days after r and omisation . The benefit obtained with treatment " A " was greater and longer lasting than that experienced using " B " , despite the fact that the same benefit was obtained in joint mobility in the two groups . Patients undergoing the experimental treatment returned to their usual occupations sooner than the controls . The results seem to confirm the hypothesis of a multifactorial involvement as a possible mechanism for the late whiplash syndrome Objective : To investigate the effect of transcutaneous electrical nerve stimulation ( TENS ) on acupuncture points and neck exercise in chronic neck pain patients . Design : A r and omized clinical trial . Setting : Hospital-based practice . Subjects : Two hundred and eighteen patients with chronic neck pain . Interventions : Subjects were r and omized into three groups , receiving either ( 1 ) TENS over the acupuncture points plus infrared irradiation ( TENS group ) ; ( 2 ) exercise training plus infrared irradiation ( exercise group ) ; or ( 3 ) infrared irradiation alone ( control ) ; twice a week for six weeks . Outcome measures : The values of verbal numeric pain scale , Northwick Park Neck Pain Question naire , and isometric neck muscle strength were assessed before , at the end of the six-week treatment , and at the six-month follow-up . Results : Results demonstrated that after the six-week treatment , significant improvement in the verbal numerical pain scale was found only in the TENS group ( 0.60±2.54 , p=0.027 ) and the exercise group ( 1.57±2.67 , p<0.001 ) . Though significant reduction in Northwick Park Neck Pain Question naire score was found in all three groups , post-hoc tests showed that both the TENS and the exercise group produced better improvement ( 0.38±0.60 % and 0.39±0.62 % respectively ) than the control group ( 0.23±0.63 % ) . Significant improvement ( p = < 0.001 to 0.03 ) in neck muscle strength was observed in all three groups , however , the improvement in the control group was not clinical ly significant and it could not be maintained at the six-month follow-up . Conclusions : After the six-week treatment , patients in the TENS and exercise group had a better and clinical ly relevant improvement in disability , isometric neck muscle strength , and pain . All the improvements in the intervention groups were maintained at the six-month follow-up |
12,105 | 30,097,022 | Conclusion Women ’s education interventions may improve the number of women seeking birth at a health care facility , but the evidence is of low quality . | Background This is a systematic review on the effectiveness of community interventions in improving maternal health care outcomes in South Asia . | Background Pakistan has high maternal mortality , particularly in the rural areas . The delay in decision making to seek medical care during obstetric emergencies remains a significant factor in maternal mortality . Methods We present results from an experimental study in rural Pakistan . Village clusters were r and omly assigned to intervention and control arms ( 16 clusters each ) . In the intervention clusters , women were provided information on safe motherhood through pictorial booklets and audiocassettes ; traditional birth attendants were trained in clean delivery and recognition of obstetric and newborn complications ; and emergency transportation systems were set up . In eight of the 16 intervention clusters , husb and s also received specially design ed education material s on safe motherhood and family planning . Pre- and post-intervention surveys on selected maternal and neonatal health indicators were conducted in all 32 clusters . A district-wide survey was conducted two years after project completion to measure any residual impact of the interventions . Results Pregnant women in intervention clusters received prenatal care and prophylactic iron therapy more frequently than pregnant women in control clusters . Providing safe motherhood education to husb and s result ed in further improvement of some indicators . There was a small but significant increase in percent of hospital deliveries but no impact on the use of skilled birth attendants . Perinatal mortality reduced significantly in clusters where only wives received information and education in safe motherhood . The survey to assess residual impact showed similar results . Conclusions We conclude that providing safe motherhood education increased the probability of pregnant women having prenatal care and utilization of health services for obstetric complications Objectives : Community-based maternal and newborn intervention packages have been shown to reduce neonatal mortality in re source -constrained setting s. This analysis uses data from a large community-based cluster-r and omized trial to assess the impact of a community-based package on cause-specific neonatal mortality and draws programmatic and policy implication s. In addition , the study shows that cause-specific mortality estimates vary substantially based on the hierarchy used in assigning cause of death , which also has important implication s for program planning . Therefore , underst and ing the methods of assigning causes of deaths is important , as is the development of new method ologies that account for multiple causes of death . The objective of this study was to estimate the effect of two service delivery strategies ( home care and community care ) for a community-based package of maternal and neonatal health interventions on cause-specific neonatal mortality rates in a rural district of Bangladesh . Study design : Within the general community of the Sylhet district in rural northeast Bangladesh . Pregnancy histories were collected from a sample of women in the study area during the year preceding the study ( 2002 ) and from all women who reported a pregnancy outcome during the intervention in years 2004 to 2005 . All families that reported a neonatal death during these time periods were asked to complete a verbal autopsy interview . Expert algorithms with two different hierarchies were used to assign causes of neonatal death , varying in placement of the preterm/low birth weight category within the hierarchy ( either third or last ) . The main outcome measure was cause-specific neonatal mortality . Result : Deaths because of serious infections in the home-care arm declined from 13.6 deaths per 1000 live births during the baseline period to 7.2 during the intervention period according to the first hierarchy ( preterm placed third ) and from 23.6 to 10.6 according to the second hierarchy ( preterm placed last ) . Conclusion : This study confirms the high burden of neonatal deaths because of infection in low re source rural setting s like Bangladesh , where most births occur at home in the absence of skilled birth attendance and care seeking for newborn illnesses is low . The study demonstrates that a package of community-based neonatal health interventions , focusing primarily on infection prevention and management , can substantially reduce infection-related neonatal mortality Background To evaluate a delivery strategy for newborn interventions in rural Bangladesh . Methods A cluster-r and omized controlled trial was conducted in Mirzapur , Bangladesh . Twelve unions were r and omized to intervention or comparison arm . All women of reproductive age were eligible to participate . In the intervention arm , community health workers identified pregnant women ; made two antenatal home visits to promote birth and newborn care preparedness ; made four postnatal home visits to negotiate preventive care practice s and to assess newborns for illness ; and referred sick neonates to a hospital and facilitated compliance . Primary outcome measures were antenatal and immediate newborn care behaviours , knowledge of danger signs , care seeking for neonatal complications , and neonatal mortality . Findings A total of 4616 and 5241 live births were recorded from 9987 and 11153 participants in the intervention and comparison arm , respectively . High coverage of antenatal ( 91 % visited twice ) and postnatal ( 69 % visited on days 0 or 1 ) home visitations was achieved . Indicators of care practice s and knowledge of maternal and neonatal danger signs improved . Adjusted mortality hazard ratio in the intervention arm , compared to the comparison arm , was 1.02 ( 95 % CI : 0.80–1.30 ) at baseline and 0.87 ( 95 % CI : 0.68–1.12 ) at endline . Primary causes of death were birth asphyxia ( 49 % ) and prematurity ( 26 % ) . No adverse events associated with interventions were reported . Conclusion Lack of evidence for mortality impact despite high program coverage and quality assurance of implementation , and improvements in targeted newborn care practice s suggests the intervention did not adequately address risk factors for mortality . The level and cause-structure of neonatal mortality in the local population must be considered in developing interventions . Programs must ensure skilled care during childbirth , including management of birth asphyxia and prematurity , and curative postnatal care during the first two days of life , in addition to essential newborn care and infection prevention and management . Trial Registration Clinical trials.gov BACKGROUND Neonatal deaths in developing countries make the largest contribution to global mortality in children younger than 5 years . 90 % of deliveries in the poorest quintile of households happen at home . We postulated that a community-based participatory intervention could significantly reduce neonatal mortality rates . METHODS We pair-matched 42 geopolitical clusters in Makwanpur district , Nepal , selected 12 pairs r and omly , and r and omly assigned one of each pair to intervention or control . In each intervention cluster ( average population 7000 ) , a female facilitator convened nine women 's group meetings every month . The facilitator supported groups through an action-learning cycle in which they identified local perinatal problems and formulated strategies to address them . We monitored birth outcomes in a cohort of 28?931 women , of whom 8 % joined the groups . The primary outcome was neonatal mortality rate . Other outcomes included stillbirths and maternal deaths , uptake of antenatal and delivery services , home care practice s , infant morbidity , and health-care seeking . Analysis was by intention to treat . The study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N31137309 . FINDINGS From 2001 to 2003 , the neonatal mortality rate was 26.2 per 1000 ( 76 deaths per 2899 livebirths ) in intervention clusters compared with 36.9 per 1000 ( 119 deaths per 3226 livebirths ) in controls ( adjusted odds ratio 0.70 [ 95 % CI 0.53 - 0.94 ] ) . Stillbirth rates were similar in both groups . The maternal mortality ratio was 69 per 100000 ( two deaths per 2899 livebirths ) in intervention clusters compared with 341 per 100000 ( 11 deaths per 3226 livebirths ) in control clusters ( 0.22 [ 0.05 - 0.90 ] ) . Women in intervention clusters were more likely to have antenatal care , institutional delivery , trained birth attendance , and hygienic care than were controls . INTERPRETATION Birth outcomes in a poor rural population improved greatly through a low cost , potentially sustainable and scalable , participatory intervention with women 's groups BACKGROUND Two recent trials have shown that women 's groups can reduce neonatal mortality in poor communities . We assessed the effectiveness of a scaled-up development programme with women 's groups to address maternal and neonatal care in three rural districts of Bangladesh . METHODS 18 clusters ( with a mean population of 27 953 [ SD 5953 ] ) in three districts were r and omly assigned to either intervention or control ( nine clusters each ) by use of stratified r and omisation . For each district , cluster names were written on pieces of paper , which were folded and placed in a bottle . The first three cluster names drawn from the bottle were allocated to the intervention group and the remaining three to control . All clusters received health services strengthening and basic training of traditional birth attendants . In intervention clusters , a facilitator convened 18 groups every month to support participatory action and learning for women , and to develop and implement strategies to address maternal and neonatal health problems . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study period ( Feb 1 , 2005 , to Dec 31 , 2007 ) . Neither study investigators nor participants were masked to treatment assignment . In a population of 229 195 people ( intervention clusters only ) , 162 women 's groups provided coverage of one group per 1414 population . The primary outcome was neonatal mortality rate ( NMR ) . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N54792066 . FINDINGS We monitored outcomes for 36 113 births ( intervention clusters , n=17 514 ; control clusters , n=18 599 ) in a population of 503 163 over 3 years . From 2005 to 2007 , there were 570 neonatal deaths in the intervention clusters and 656 in the control clusters . Cluster-level mean NMR ( adjusted for stratification and clustering ) was 33.9 deaths per 1000 livebirths in the intervention clusters compared with 36.5 per 1000 in the control clusters ( risk ratio 0.93 , 95 % CI 0.80 - 1.09 ) . INTERPRETATION For participatory women 's groups to have a significant effect on neonatal mortality in rural Bangladesh , detailed attention to programme design and context ual factors , enhanced population coverage , and increased enrolment of newly pregnant women might be needed . FUNDING Women and Children First , the UK Big Lottery Fund , Saving Newborn Lives , and the UK Department for International Development IMPORTANCE Community-based interventions can reduce neonatal mortality when health systems are weak . Population coverage of target groups may be an important determinant of their effect on behavior and mortality . A women 's group trial at coverage of 1 group per 1414 population in rural Bangladesh showed no effect on neonatal mortality , despite a similar intervention having a significant effect on neonatal and maternal death in comparable setting s. OBJECTIVE To assess the effect of a participatory women 's group intervention with higher population coverage on neonatal mortality in Bangladesh . DESIGN A cluster r and omized controlled trial in 9 intervention and 9 control clusters . SETTING Rural Bangladesh . PARTICIPANTS Women permanently residing in 18 unions in 3 districts and accounting for 19 301 births during the final 24 months of the intervention . INTERVENTIONS Women 's groups at a coverage of 1 per 309 population that proceed through a participatory learning and action cycle in which they prioritize issues that affected maternal and neonatal health and design and implement strategies to address these issues . MAIN OUTCOMES AND MEASURES Neonatal mortality rate . RESULTS Analysis included 19 301 births during the final 24 months of the intervention . More than one-third of newly pregnant women joined the groups . The neonatal mortality rate was significantly lower in the intervention arm ( 21.3 neonatal deaths per 1000 live births vs 30.1 per 1000 in control areas ) , a reduction in neonatal mortality of 38 % ( risk ratio , 0.62 [ 95 % CI , 0.43 - 0.89 ] ) when adjusted for socioeconomic factors . The cost-effectiveness was US $ 220 to $ 393 per year of life lost averted . Cause-specific mortality rates suggest reduced deaths due to infections and those associated with prematurity/low birth weight . Improvements were seen in hygienic home delivery practice s , newborn thermal care , and breastfeeding practice s. CONCLUSIONS AND RELEVANCE Women 's group community mobilization , delivered at adequate population coverage , is a highly cost-effective approach to improve newborn survival and health behavior indicators in rural Bangladesh . TRIAL REGISTRATION is rct n.org Identifier : IS RCT N01805825 Background Public health interventions are increasingly evaluated using cluster-r and omised trials in which groups rather than individuals are allocated r and omly to treatment and control arms . Outcomes for individuals within the same cluster are often more correlated than outcomes for individuals in different clusters . This needs to be taken into account in sample size estimations for planned trials , but most estimates of intracluster correlation for perinatal health outcomes come from hospital-based studies and may therefore not reflect outcomes in the community . In this study we report estimates for perinatal health outcomes from community-based trials to help research ers plan future evaluations . Methods We estimated the intracluster correlation and the coefficient of variation for a range of outcomes using data from five community-based cluster r and omised controlled trials in three low-income countries : India , Bangladesh and Malawi . We also performed a simulation exercise to investigate the impact of cluster size and number of clusters on the reliability of estimates of the coefficient of variation for rare outcomes . Results Estimates of intracluster correlation for mortality outcomes were lower than those for process outcomes , with narrower confidence intervals throughout for trials with larger numbers of clusters . Estimates of intracluster correlation for maternal mortality were particularly variable with large confidence intervals . Stratified r and omisation had the effect of reducing estimates of intracluster correlation . The simulation exercise showed that estimates of intracluster correlation are much less reliable for rare outcomes such as maternal mortality . The size of the cluster had a greater impact than the number of clusters on the reliability of estimates for rare outcomes . Conclusions The breadth of intracluster correlation estimates reported here in terms of outcomes and context s will help research ers plan future community-based public health interventions around maternal and newborn health . Our study confirms previous work finding that estimates of intracluster correlation are associated with the prevalence of the outcome of interest , the nature of the outcome of interest ( mortality or behavioural ) and the size and number of clusters . Estimates of intracluster correlation for maternal mortality need to be treated with caution and a range of estimates should be used in planning future trials BACKGROUND Newborn deaths account for 57 % of deaths in children younger than 5 years in Pakistan . Although a large programme of trained lady health workers ( LHWs ) exists , the effectiveness of this training on newborn outcomes has not been studied . We aim ed to evaluate the effectiveness of a community-based intervention package , principally delivered through LHWs working with traditional birth attendants and community health committees , for reduction of perinatal and neonatal mortality in a rural district of Pakistan . METHODS We undertook a cluster r and omised trial between February , 2006 , and March , 2008 , in Hala and Matiari subdistricts , Pakistan . Catchment areas of primary care facilities and all affiliated LHWs were used to define clusters , which were allocated to intervention and control groups by restricted , stratified r and omisation . The intervention package delivered by LHWs through group sessions consisted of promotion of antenatal care and maternal health education , use of clean delivery kits , facility births , immediate newborn care , identification of danger signs , and promotion of careseeking ; control clusters received routine care . Independent data collectors undertook quarterly household surveillance to capture data for births , deaths , and household practice s related to maternal and newborn care . Data collectors were masked to cluster allocation ; those analysing data were not . The primary outcome was perinatal and all-cause neonatal mortality . Analysis was by intention to treat . This trial is registered , IS RCT N16247511 . FINDINGS 16 clusters were assigned to intervention ( 23,353 households , 12,391 total births ) and control groups ( 23,768 households , 11,443 total births ) . LHWs in the intervention clusters were able to undertake 4428 ( 63 % ) of 7084 planned group sessions , but were only able to visit 2943 neonates ( 24 % ) of a total 12,028 livebirths in their catchment villages . Stillbirths were reduced in intervention clusters ( 39·1 stillbirths per 1000 total births ) compared with control ( 48·7 per 1000 ; risk ratio [ RR ] 0·79 , 95 % CI 0·68 - 0·92 ; p=0·006 ) . The neonatal mortality rate was 43·0 deaths per 1000 livebirths in intervention clusters compared with 49·1 per 1000 in control groups ( RR 0·85 , 0·76 - 0·96 ; p=0·02 ) . INTERPRETATION Our results support the scale-up of preventive and promotive maternal and newborn interventions through community health workers and emphasise the need for attention to issues of programme management and coverage for such initiatives to achieve maximum potential . FUNDING WHO ; Saving Newborn Lives Program of Save the Children USA , funded by the Bill & Melinda Gates Foundation BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) Background Neonatal mortality rates are high in rural Nepal where more than 90 % of deliveries are in the home . Evidence suggests that death rates can be reduced by interventions at community level . We describe an intervention which aim ed to harness the power of community planning and decision making to improve maternal and newborn care in rural Nepal . Methods The development of 111 women 's groups in a population of 86 704 in Makwanpur district , Nepal is described . The groups , facilitated by local women , were the intervention component of a r and omized controlled trial to reduce perinatal and neonatal mortality rates . Through participant observation and analysis of reports , we describe the implementation of this intervention : the community entry process , the facilitation of monthly meetings through a participatory action cycle of problem identification , community planning , and implementation and evaluation of strategies to tackle the identified problems . Results In response to the needs of the group , participatory health education was added to the intervention and the women 's groups developed varied strategies to tackle problems of maternal and newborn care : establishing mother and child health funds , producing clean home delivery kits and operating stretcher schemes . Close linkages with community leaders and community health workers improved strategy implementation . There were also indications of positive effects on group members and health services , and most groups remained active after 30 months . Conclusion A large scale and potentially sustainable participatory intervention with women 's groups , which focused on pregnancy , childbirth and the newborn period , result ed in innovative strategies identified by local communities to tackle perinatal care problems Background Skilled attendance at delivery is an important indicator in monitoring progress towards Millennium Development Goal 5 to reduce the maternal mortality ratio by three quarters between 1990 and 2015 . In addition to professional attention , it is important that mothers deliver their babies in an appropriate setting , where life saving equipment and hygienic conditions can also help reduce the risk of complications that may cause death or illness to mother and child . Over the past decade interest has grown in examining influences on care-seeking behavior and this study investigates the determinants of place of delivery in rural India , with a particular focus on assessing the relative importance of community access and economic status . Methods A descriptive analysis of trends in place of delivery using data from two national representative sample surveys in 1992 and 1998 is followed by a two-level ( child/mother and community ) r and om-effects logistical regression model using the second survey to investigate the determinants . Results In this investigation of institutional care seeking for child birth in rural India , economic status emerges as a more crucial determinant than access . Economic status is also the strongest influence on the choice between a private-for-profit or public facility amongst institutional births . Conclusion Greater availability of obstetric services will not alone solve the problem of low institutional delivery rates . This is particularly true for the use of private-for-profit institutions , in which the distance to services does not have a significant adjusted effect . In the light of these findings a focus on increasing dem and for existing services seems the most rational action . In particular , financial constraints need to be addressed , and results support current trials of dem and side financing in India A total of 121 maternal deaths , identified through multiple- source surveillance in 400 villages in Maharashtra , were prospect ively enrolled during 1993 - 95 in a population -based case-control study , which compared deaths with the survivors of similar pregnancy complications . The cases took significantly longer to seek care and to make the first health contact after the decision to seek care was taken . They also travelled significantly greater distances through a greater number of health facilities before appropriate treatment was started . Multivariate analysis showed the negative effect of excessive referrals and the protective effect of the following : residing in and not away from the village ; presence of a resident nurse in the village ; having an educated husb and and a trained attendant at delivery ; and being at the woman 's parents ' home at the time of illness . Other significant findings showed that deaths due to domestic violence were the second-largest cause of deaths in pregnancy , that more than two-thirds of maternal deaths were underreported in official records , and that liveborn infants of maternal deaths had a markedly higher risk of dying in the first year of life . This study points to the need for information-education-communication ( IEC ) efforts to increase family ( especially male ) preparedness for emergencies , de central ized obstetric management with effective triage , and a restructuring of the referral system The role of involving prospect i ve fathers in the care of pregnant women attending the Mother Craft Clinic of the Malavani Health Center in Bombay , India was evaluated . Beginning in October 1982 , pregnant women attending the Clinic were requested to ask their hus and s to meet the resident medical officer of the center who was available on the premises of the Center on all days and evenings including the holidays . 1 of the medico-social workers explained to the women the reason and the need for their husb and s coming and meeting the doctor at the Center . The outcome of the maternal health care program for the 270 women whose husb and s were invited and came ( Group 1 ) was compared with the outcome of the same program , under the same roof , for 405 women whose husb and s could not be invited ( Group 2 ) . The husb and s who attended the center were educated individually and in groups about their role in nutrition and health of their wives during pregnancy and their responsibility in subsequent child rearing . The physiology of pregnancy , complications of pregnancy , and the possible ways and means of preventing the complications were explained in detail . The husb and s were also told to encourage their wives to attend the antenatal clinic of the center as often as possible . There was no difference in the socioeconomic , educational , cultural , and religious background of the 2 groups of women who were similar in parity distribution . The main difference between the 2 groups was a significantly lower perinatal mortality in Group 1 . Only 60 of the 405 Group 2 women were considered eligible for postpartum sterilization ( para 3 and higher ) . In contrast , 41 of the 270 Group 1 women were considered eligible for postpartum sterilization and 110 women accepted . The excess of those who accepted over those who were eligible came form the lower paras . This effort confirms that the involvement of prospect i ve fathers is possible and pays good dividends even in an uneducated and low socioeconomic connumity such as that in Malavani The persistence of high perinatal and neonatal mortality rates in many developing countries make efforts to improve perinatal care in the home and at local health facilities important public health concerns . We describe a study which aims to evaluate a community-level participatory intervention in rural Nepal . The effectiveness of community-based action research interventions with mothers and other key members of the community in improving perinatal health outcomes is being examined using a cluster r and omized , controlled trial covering a population of 28,000 married women of reproductive age . The unit of r and omization was the village development committee ( VDC ) : 12 VDCs receive the intervention while 12 serve as controls . The key elements of the intervention are the activities of female facilitators , each of whom works in one VDC facilitating the activities of women 's groups in addressing problems in pregnancy , childbirth and the newborn period . Each group moves through a participatory planning cycle of assessment , sharing experiences , planning , action and re assessment , with the aim of improving essential maternal and newborn care . Outcomes assessed are neonatal and perinatal mortality rates , changes in patterns of home care , health care seeking and referral . The study also aims to generate programmatic information on the process of implementation in communities BACKGROUND Mobile text messaging is a potentially powerful tool for behaviour change because it is widely available , inexpensive , and instant . AIMS To evaluate whether mobile Text Messaging Service is a feasible mode of raising knowledge regarding maternal and child health ( MCH ) and to explore issues related to mobile text messages as a mode of health education . METHOD A community-based intervention study was conducted from January to June 2013 in six r and omly selected villages of Vellore district , Tamil Nadu . A multi-stage sampling technique was followed : 120 individuals from 120 households ( 30 clusters in six villages ) were contacted . Data was collected using a pretested question naire by house-to-house visits in three phases : 1 ) baseline assessment of aptitude towards text messages ; 2 ) intervention : sending MCH-related text messages ; and 3 ) end-line assessment to evaluate the increase in knowledge level . Qualitative data regarding mobile text messages as a mode of health education was explored . Quantitative data was analysed using SPSS version 17.0 and qualitative data by Anthropac software . RESULTS Of the individuals surveyed , 69.17 per cent and 52.5 per cent were " able to read " and " type and send " text messages , respectively . Seventy per cent of individuals were willing to receive health information via text messages , and 98.33 per cent believed text messages could effectively spread health messages . A significant increase in knowledge was observed following text messages . Male gender and subjects ' ability to read text messages were significantly associated . Factors related to mobile phone use include minimum economic burden , easy availability , portability , and ease of use . Factors related to mobile text messages as a mode of health message delivery include direct receipt of information , mass reach , the absence of regional language font in many h and sets , and illiterate individuals being unable to read messages . CONCLUSION In rural areas , mobile text messages have the potential to deliver health messages regarding MCH Objectives . We evaluated the effectiveness of the Sure Start project , which was implemented in 7 districts of Uttar Pradesh , India , to improve maternal and newborn health . Methods . Interventions were implemented at 2 r and omly assigned levels of intensity . Forty percent of the areas received a more intense intervention , including community-level meetings with expectant mothers . A baseline survey consisted of 12 000 women who completed pregnancy in 2007 ; a follow-up survey was conducted for women in 2010 in the same villages . Our quantitative analyses provide an account of the project 's impact . Results . We observed significant health improvements in both intervention areas over time ; in the more intensive intervention areas , we found greater improvements in care-seeking and healthy behaviors . The more intensive intervention areas did not experience a significantly greater decline in neonatal mortality . Conclusions . This study demonstrates that community-based efforts , especially mothers ' group meetings design ed to increase care-seeking and healthy behaviors , are effective and can be implemented at large scale Pregnancy and the events surrounding it are generally viewed as feminine issues exclusively for women . In sub-Saharan Africa , believing that pregnancy and the events that follow are guided by nature , a lot of superstition is attributed in the event of complications , which result in poor maternal outcomes . Maternal mortality remains a public health challenge worldwide , and Nigeria has one of the highest levels of maternal mortality in the world ( 545 per 100,000 live births ) . The involvement of men in ensuring and enhancing maternal health was a great idea hatched at the Cairo conference in 1994 , but since then , not much has been done in practical terms in most of the developing world . This study is aim ed at assessing the level of male involvement in their spouses ’ reproductive health events before pregnancy , during pregnancy , delivery and peuperium . A descriptive cross-sectional study design in which question naires were incorporated with an in-depth interview was used and a multistage sampling technique was used to select respondents . After house numbering , a total of 400 houses were selected from a cluster of four quarters in Patani Town . Participants were systematic ally sample d from each household using r and om number table . Results from data collected on the study indicated that ( 61.1 % ) of men were aware of maternal health issues and the level of education was shown to have significant relationship ( χ² = 5.139 , df = 3 , p = 0.162 ) with the knowledge of maternal health issues . Though the level of male involvement in safe motherhood was shown to be of good proportion , strategies to create awareness on male support for their parous spouses should be given a broader frontier , both in clinics , household and community levels . Men should be more involved than before , as they have a priceless role to play towards a significant improvement in maternal health . The Government , development partners and NGOs at all levels should be committed with a strong political will in this regard BACKGROUND A quarter of the world 's neonatal deaths and 15 % of maternal deaths happen in India . Few community-based strategies to improve maternal and newborn health have been tested through the country 's government-approved Accredited Social Health Activists ( ASHAs ) . We aim ed to test the effect of participatory women 's groups facilitated by ASHAs on birth outcomes , including neonatal mortality . METHODS In this cluster-r and omised controlled trial of a community intervention to improve maternal and newborn health , we r and omly assigned ( 1:1 ) geographical clusters in rural Jharkh and and Odisha , eastern India to intervention ( participatory women 's groups ) or control ( no women 's groups ) . Study participants were women of reproductive age ( 15 - 49 years ) who gave birth between Sept 1 , 2009 , and Dec 31 , 2012 . In the intervention group , ASHAs supported women 's groups through a participatory learning and action meeting cycle . Groups discussed and prioritised maternal and newborn health problems , identified strategies to address them , implemented the strategies , and assessed their progress . We identified births , stillbirths , and neonatal deaths , and interviewed mothers 6 weeks after delivery . The primary outcome was neonatal mortality over a 2 year follow up . Analyses were by intention to treat . This trial is registered with IS RCT N , number IS RCT N31567106 . FINDINGS Between September , 2009 , and December , 2012 , we r and omly assigned 30 clusters ( estimated population 156 519 ) to intervention ( 15 clusters , estimated population n=82 702 ) or control ( 15 clusters , n=73 817 ) . During the follow-up period ( Jan 1 , 2011 , to Dec 31 , 2012 ) , we identified 3700 births in the intervention group and 3519 in the control group . One intervention cluster was lost to follow up . The neonatal mortality rate during this period was 30 per 1000 livebirths in the intervention group and 44 per 1000 livebirths in the control group ( odds ratio [ OR ] 0.69 , 95 % CI 0·53 - 0·89 ) . INTERPRETATION ASHAs can successfully reduce neonatal mortality through participatory meetings with women 's groups . This is a scalable community-based approach to improving neonatal survival in rural , underserved areas of India . FUNDING Big Lottery Fund ( UK ) |
12,106 | 30,113,550 | However , these effects did not always persist in the long-term .
Conclusions : These findings suggest that multisensory stimulation could be an effective intervention for managing NPS in older adults with major NCD in a mild to severe stage , particularly for managing behavioral symptoms such as agitation .
This research provides an indication of the likely effect of the multisensory stimulation on NPS such as agitation and anxiety , as well on cognitive status | Objective : The objective of the review was to synthesize the effectiveness of multisensory stimulation in managing neuropsychiatric symptoms ( NPS ) in older adults with major neurocognitive disorder ( NCD ) .
Introduction : Major neurocognitive disorder is characterized by changes in specific cognitive domains with a progressive deterioration in cognitive ability and capacity for independent living .
Most older adults with this condition have one or more concomitant symptoms known as NPS .
Evidence shows that nonpharmacological therapies have been effective in controlling these symptoms , with multisensory stimulation attracting further investigation . | OBJECTIVES To investigate the effectiveness of snoezelen , integrated in 24-hour daily care , on the behavior and mood of demented nursing home residents . DESIGN Quasiexperimental pre- and posttest design . SETTING Twelve psychogeriatric wards of six nursing homes , spread over different parts of the Netherl and s. PARTICIPANTS One hundred twenty-five patients with moderate to severe dementia and care dependency were included in the pretest and 128 in the posttest ; 61 were completers ( included in both pre- and posttest ) . INTERVENTION Experimental subjects received an individual 24-hour snoezel program , based on family history taking and stimulus preference screening . Caregivers were trained , and ( organizational ) adaptations were made to fulfill the conditions for resident-oriented snoezel care . The control group received usual nursing home care . MEASUREMENTS Observations were made on the wards using subscales of the Dutch Behavior Observation Scale for Psychogeriatric In patients , the Dutch version of the Cohen-Mansfield Agitation Inventory , and the Cornell Scale for Depression in Dementia . Independent assessors observed video recordings of morning care and rated residents ' behavior and mood using INTERACT and FACE , respectively . RESULTS Residents receiving snoezel care demonstrated a significant treatment effect with respect to their level of apathetic behavior , loss of decorum , rebellious behavior , aggressive behavior , and depression . During morning care , the experimental subjects showed significant changes in well-being ( mood , happiness , enjoyment , sadness ) and adaptive behavior ( responding to speaking , relating to caregiver , normal-length sentences ) . CONCLUSION Snoezel care particularly seems to have a positive effect on disturbing and withdrawn behavior . The results suggest that a 24-hour integrated snoezel program has a generalizing effect on the mood and behavior of demented residents Long-term effects of multisensory stimulation were assessed using a “ Snoezelen ” room on older residents with dementia . Thirty patients were r and omly assigned to 3 groups : multisensory stimulation environment ( MSSE ) group , individualized activities ( activity ) group , and control group . The MSSE and activity groups participated in two 30-minute weekly individualized intervention sessions over 16 weeks . Pre- , mid- , posttrial , and 8-week follow-up behavior , mood , cognitive , and functional impairment in basic activities of daily living were registered . Items included in the physically nonaggressive behavior factor improved significantly in post- versus pretrial in the MSSE group compared to the activity group , with no significant differences between MSSE and control groups . The MSSE and activity groups demonstrated behavior improvements and higher scores on the Cohen-Mansfield agitation inventory , verbal agitated behavior factor , and Neuropsychiatric Inventory – Nursing Home , with no significant differences between groups . The MSSE could have long-term positive effects on such neuropsychiatric symptoms in older people with dementia OBJECTIVES Dementia is the disease most frequently leading to admission in long-term care institutions , primarily because persons with this disease exhibit several behavioral problems . The objective of this study was to measure the efficacy of the sensory integration program developed by Ross and Burdick in improving the functioning of persons with dementia . METHOD Forty subjects with dementia ( 28 women , 12 men , mean age of 78.4 years ) in three different institutional setting s in Quebec City , Canada , were r and omly assigned to the study ( n = 22 ) or control ( n = 18 ) group . Subjects in the study group participated in three 45-min sessions of a sensory integration program per week for 10 weeks . Outcomes were measured using the Revised Memory and Behavior Problems Checklist and the Psychogeriatric Scale of Basic Activities of Daily Living . RESULTS The sensory integration program had no significant effect on the behaviors of the study group . CONCLUSION Before this type of program is labeled inefficacious , other studies are necessary to determine whether modifying the frequency of sessions , the number of subjects , and the measuring instruments would lead to similar results BACKGROUND Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia , but although some studies have found it to be helpful , most are small and uncontrolled . METHODS This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards . The participants were 38 patients with moderate or severe Alzheimer 's disease ( AD ) assigned r and omly to a music therapy group and a control group . RESULTS The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer 's Disease Rating Scale ( BEHAVE-AD ) . There was also a significant reduction in the sum of scores of activity disturbances , aggressiveness and anxiety . Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly . Four weeks later the effects had mostly disappeared . CONCLUSIONS Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD . This is in line with the results of some non-controlled studies on music therapy in dementia BACKGROUND Over recent years multi-sensory stimulation ( MSS ) has become an increasingly popular approach to care and is used in several centres throughout Europe . This popularity could be explained by the limited alternatives available to staff and a widely held belief that MSS is a friendly and highly humane approach . A r and omized controlled trial was therefore essential to evaluate the effectiveness and extent of the benefits of MSS . AIM To assess whether MSS is more effective in changing the behaviour , mood and cognition of older adults with dementia than a control of activity ( playing card games , looking at photographs , doing quizzes , etc . ) . METHODS A total of 136 patients from three countries [ United Kingdom ( UK ) , the Netherl and s and Sweden ] were r and omized to MSS or activity groups . Patients participated in eight 30-minute sessions over 4 weeks . Ratings of behaviour and mood were taken before , during and after sessions to investigate immediate effects . Pre- , mid- , post-trial and follow-up assessment s were taken to investigate any generalization of effects to cognition and behaviour and mood at home/on the ward or at the day hospital . RESULTS There were limited short-term improvements for both the MSS and activity groups immediately after sessions , and limited short-term improvements between the groups during sessions . There were no significant differences between the groups when assessing change in behaviour , mood or cognition at home/on the ward or at the day hospital . In the UK , however , behaviour at the day hospital for both groups remained stable during the trial but deteriorated once the sessions had stopped , and active/disturbed behaviour at home improved but likewise deteriorated once sessions had stopped . CONCLUSIONS Overall , MSS was found to be no more effective than an activity in changing the behaviour , mood or cognition of patients with dementia in the short- or long-term This study investigates the effects of emotion‐oriented care on the behavior of elderly people with cognitive impairment and behavioral problems . This approach is mainly based on the validation approach , but also uses insights from other approaches like reminiscence and sensory stimulation OBJECTIVES To test the effects of an intervention that helps families manage distressing behaviors in family members with dementia . DESIGN Two-group r and omized trial . SETTING In home . PARTICIPANTS Two hundred seventy-two caregivers and people with dementia . INTERVENTION Up to 11 home and telephone contacts over 16 weeks by health professionals who identified potential triggers of patient behaviors , including communication and environmental factors and patient undiagnosed medical conditions ( by obtaining blood and urine sample s ) and trained caregivers in strategies to modify triggers and reduce their upset . Between 16 and 24 weeks , three telephone contacts reinforced strategy use . MEASUREMENTS Primary outcomes were frequency of targeted problem behavior and caregiver upset with and confidence managing it at 16 weeks . Secondary outcomes were caregiver well-being and management skills at 16 and 24 weeks and caregiver perceived benefits . Prevalence of medical conditions for intervention patients were also examined . RESULTS At 16 weeks , 67.5 % of intervention caregivers reported improvement in targeted problem behavior , compared with 45.8 % of caregivers in a no-treatment control group ( P=.002 ) , and reduced upset with ( P=.03 ) and enhanced confidence managing ( P=.01 ) the behavior . Additionally , intervention caregivers reported less upset with all problem behaviors ( P=.001 ) , less negative communication ( P=.02 ) , less burden ( P=.05 ) , and better well-being ( P=.001 ) than controls . Fewer intervention caregivers had depressive symptoms ( 53.0 % ) than control group caregivers ( 67.8 % , P=.02 ) . Similar caregiver outcomes occurred at 24 weeks . Intervention caregivers perceived more study benefits ( P<.05 ) , including ability to keep family members home , than controls . Blood and urine sample s of intervention patients with dementia showed that 40 ( 34.1 % ) had undiagnosed illnesses requiring physician follow-up . CONCLUSION Targeting behaviors up setting to caregivers and modifying potential triggers improves symptomatology in people with dementia and caregiver well-being and skills The purpose of this pilot study was to explore the feasibility and effectiveness of using multisensory environments ( MSE ) in the home of people with dementia . A qualitative research design was used , which included semi-structured interviews and self-rated caregiver observation checklists . Field notes and audio recorded interviews were transcribed for data analysis . Data were reduced and coded for theme identification . Positive and negative effects of the use of MSE in the home on the behaviors of the person with dementia , caregiver burden , and family interpersonal relationships were revealed . Overall , MSE was discovered to promote a relaxing and calm environment in the home , which helped the person with dementia attend more to their immediate surroundings , and to improve family interactions . Although the majority of caregivers reported they enjoyed the MSE , they acknowledged their disappointment in the MSE as not providing more caregiver respite The objective of this study was to compare the effects of a multisensory stimulation environment ( MSSE ) and individualized music sessions on agitation , emotional and cognitive status , and dementia severity in a sample of institutionalized patients with severe dementia . Twenty-two participants with a diagnosis of severe or very severe dementia were r and omly assigned to two groups : MSSE and individualized music sessions . Both groups participated in two 30-min weekly sessions over 16 weeks . Outcomes were agitation ( Cohen-Mansfield Agitation Inventory , CMAI ) , mood ( Cornell Scale for Depression in Dementia , CSDD ) , anxiety ( Rating Anxiety in Dementia , RAID ) , cognitive function ( Severe Mini-Mental State Examination , SMMSE ) , and the overall severity of dementia ( Bedford Alzheimer Nursing Severity Scale , BANS-S ) . They were assessed at baseline ( pre-trial ) , in the middle ( mid-trial ) , at the end of the intervention ( post-trial ) , and 8 weeks after the intervention ( follow-up ) . Patients in the MSSE group showed significant improvement in their RAID and BANS-S scores compared with the individualized music group post- versus pre-trial . With regard to agitation , there was improvement during the intervention in both the MSSE and individualized music groups in the CMAI total score after 16 weeks of intervention , with no significant differences between the groups . The results suggest that MSSE could have better effects on anxiety symptoms and dementia severity in comparison with individualized music sessions in elderly patients with severe dementia OBJECTIVES To investigate the effects of lavender olfactory stimulation intervention on fall incidence in elderly nursing home residents . DESIGN R and omized placebo-controlled trial . SETTING Three r and omly selected nursing homes in northern Japan . PARTICIPANTS One hundred and forty-five nursing home residents aged 65 and older . INTERVENTION Participants were r and omly assigned to the lavender ( n = 73 ) or placebo group ( n = 72 ) for a 360-day study period . The lavender group received continuous olfactory stimulation from a lavender patch . The placebo group received an unscented patch . MEASUREMENT The primary outcome measure was resident falls . Other measurements taken at baseline and 12 months included functional ability ( assessed using the Barthel Index ) , cognitive function ( Mini-Mental State Examination ( MMSE ) ) , and behavioral and psychological problems associated with dementia ( Cohen-Mansfield Agitation Inventory ( CMAI ) ) . RESULTS There were fewer fallers in the lavender group ( n = 26 ) than in the placebo group ( n = 36 ) ( hazard ratio (HR)=0.57 , 95 % confidence interval ( CI ) = 0.34 - 0.95 ) and a lower incidence rate in the lavender group ( 1.04 per person-year ) than in the placebo group ( 1.40 per person-year ) ( incidence rate ratio = 0.51 , 95 % CI = 0.30 - 0.88 ) . The lavender group also had a significant decrease in CMAI score ( P = .04 ) from baseline to follow-up in a per protocol analysis . CONCLUSION Lavender olfactory stimulation may reduce falls and agitation in elderly nursing home residents ; further research is necessary to confirm these findings Objective : To investigate whether behavioural , motor and physiological responses of individuals with Huntington 's disease ( HD ) to a controlled multisensory environment ( MSE ) are effective as a therapeutic ( sustained effects ) or leisure ( immediate effects ) activity . Design : Pilot study – a r and omized , controlled , two-group design . Setting : Specialist residential unit for people with mid-late stage HD . Subjects : Twelve patients with HD ( one subject from each group dropped out during the study after week 8 due to medical complications ) . Interventions : Patients attended eight , 30-minute sessions over a four-week period , of multisensory stimulation ( MSE , treatment group ) or relaxation activities ( control group ) . Main outcome measures : Between-group comparisons for changes between assessment sessions for two behavioural assessment s : Rehabilitation Evaluation – Hall and Baker ( REHAB ) , Behaviour and Mood Disturbance Scale ( BMD ) ; a motor assessment : the dyskinesia section of the St Hans Rating Scale ( SHRS ) ; physiological measures : blood pressure , heart rate and respiratory rate . Secondary measures during intervention sessions included behavioural assessment using the Interact . Results : There were no significant differences found between the groups for any main outcome measures made between sessions . The MSE group showed some positive effects within-sessions , with the Interact showing significant between-group differences in immediate effects on mood ( p = 0.028 ) . There was also a significantly different change over time for within-session changes in stimulation levels ( p = 0.0002 ) and mood ( p = 0.0001 ) between the groups . No physiological effects were observed in relation to sessions in either group . Two MSE subjects underwent changes in medication during the study period A r and omized , controlled , single-blinded , between group study of 24 participants with moderate to severe dementia was conducted on a geriatric psychiatric unit . All participants received pharmacological therapy , occupational therapy , structured hospital environment , and were r and omized to receive multi sensory behavior therapy ( MSBT ) or a structured activity session . Greater independence in activities of daily living ( ADLs ) was observed for the group treated with MSBT and st and ard psychiatric inpatient care on the Katz Index of Activities of Daily Living ( KI-ADL ; P = 0.05 ) than st and ard psychiatric inpatient care alone . The combination treatment of MSBT and st and ard psychiatric care also reduced agitation and apathy greater than st and ard psychiatric inpatient care alone as measured with the Pittsburgh Agitation Scale and the Scale for the Assessment of Negative Symptoms in Alzheimer 's Disease ( P = 0.05 ) . Multiple regression analysis predicted that within the multi-sensory group , activities of daily living ( KI-ADL ) increased as apathy and agitation reduced ( R2 = 0.42 ; p = 0.03 ) . These data suggest that utilizing MSBT with st and ard psychiatric inpatient care may reduce apathy and agitation and additionally improve activities of daily living in hospitalized people with moderate to severe dementia more than st and ard care alone Objective : To investigate the influence of multisensory stimulations in a Snoezelen room on the balance of individuals with dementia . Design : R and omized controlled trial . Setting : Canadian long-term care home . Participants : Twenty-four residents ( average age 86 years ) , in a long-term care home diagnosed with dementia , were assigned r and omly to intervention and control groups . Nineteen participants completed the study . Interventions : Nine intervention group participants completed 30-minute Snoezelen room sessions twice a week for six weeks . Sessions were guided by participants ’ preferences for stimulation . Interactions with tactile , visual and proprioceptive sensations were encouraged . Ten control group participants received an equal amount of volunteer visits . Main outcome measures : The Functional Reach Test , the eyes-open Sharpened Romberg and the Timed Up and Go Test with and without dual task , assessed static and dynamic balance at baseline and after the intervention . Falls frequencies were recorded six weeks before , during and after intervention . A journal was kept of observations in Snoezelen room . Results : Split-plot MANOVA analyses revealed no significant effects of unstructured Snoezelen room sessions on participants ’ balance . There were no multivariate effects of time ( F(4,14 ) = 1.13 , P = 0.38 ) or group ( F(4,14 ) = 0.63 , P = 0.65 ) . Group membership did not alter falls frequency . However , observations of participants ’ interactions with elements of the Snoezelen room , such as imagery-induced head and eye movements , vibrating sensations and kicking activities , captured events that can be used to create specific multisensory balance-enhancing stimulations . Conclusions : Although the null hypothesis was not rejected , further investigation of a potential to influence balance in individuals with dementia through Snoezelen room intervention in long-term care homes is warranted Agitation is not only a frequent and disturbing behavior for many patients with dementia , but it also troubles their caregivers and families . Many serious problems and side effects are associated with the use of medications to treat agitation ; therefore , alternative approaches to treating agitation must be assessed . The current article presents results from a quality improvement pilot project that examined the usefulness of a specially design ed , multisensory room intervention for geriatric psychiatric in patients with mild to moderate agitation . Thirty-two visits to the sensory room were made by 13 in patients with dementia . A significant decrease occurred in the Pittsburgh Agitation Scale ( PAS ) total scores over time from pre-room to post-room intervention , as well as 1-hour post-room intervention ( F = 95.3 , p < 0.001 ) . Significant effects were found for all PAS subscales ( i.e. , aberrant vocalizations , motor agitation , and resistance to care ) , with the exception of the aggression subscale . The multisensory room intervention was effective in decreasing some symptoms of agitation in the geriatric psychiatric patient , thus contributing to positive patient , family , and nursing outcomes OBJECTIVES To investigate short-term effects of Multi-Sensory Stimulation ( MSS ) on behaviour , mood and cognition of older adults with dementia , the generalization of effects to day hospital and home environments and the endurance of any effects over time . DESIGN A r and omized controlled trial comparing MSS with a credible control of one-to-one activities . METHODS Fifty patients with diagnoses of moderate to severe dementia were r and omized to either MSS or Activity groups . Patients participated in eight 30-minute sessions over a 4-week period . Ratings of behaviour and mood were taken before , during and after sessions to investigate immediate effects . Pre , mid , post-trial , and follow-up assessment s were taken to investigate any generalization of effects on cognition , behaviour at the day hospital and behaviour and mood at home and endurance of effects once sessions had ceased . RESULTS Immediately after MSS and Activity sessions patients talked more spontaneously , related better to others , did more from their own initiative , were less bored/inactive , and were more happy , active or alert . Both groups were more attentive to their environment than before , with a significantly greater improvement from the MSS group . At the day hospital , patients in the Activity group improved on their ' speech skills ' ( amount of speech ; initiation of speech ) , whereas the MSS group remained unchanged during the trial . The MSS group showed a significant improvement in mood and behaviour at home compared to the Activity group whose behaviour deteriorated . No longer-term benefits were shown ; indeed , behaviour declined sharply during the month follow-up period . CONCLUSIONS Both MSS and Activity sessions appear to be effective and appropriate therapies for people with dementia Background : Dementia in the elderly is a common , debilitating condition . Residents in long-term care facilities present with a number of challenging behaviors . Pharmacological management is not always helpful . Alternative approaches are needed . Methods : Multisensory stimulation ( MSS ) was developed to address sensory stimulation imbalance . In this pilot 24-week single-blinded , r and omized controlled study , the authors examined the effect of MSS when given for 12 weeks in either 1 or 3 sessions per week with a control group . Results : There is a trend for better outcomes as measured by daily observation scales ( DOS ) or Clinical Global Impression-Improvement ( CGI-I ) with the increase of sessions of treatment per week . This became statistically significant at weeks 8 ( DOS ) and 12 ( CGI ) . This difference continued for 12 additional weeks after treatment ended . Conclusions : MSS may be a useful addition to the care of elderly patients with dementia . A larger double-blind r and omized control study is required The objective of this study was to compare the effect of multisensory stimulation environment ( MSSE ) and one-to-one activity sessions in the symptomatology of elderly individuals with severe dementia . Thirty-two participants were r and omly assigned to the following 3 groups : MSSE , activity , and control group . The MSSE and activity groups participated in two 30-minute weekly sessions over 16 weeks . Pre- , mid- , and posttrial ; 8-week follow-up behavior ; mood ; cognitive status ; and dementia severity were registered . Patients in the MSSE group demonstrated a significant improvement in the Neuropsychiatric Inventory and Bedford Alzheimer Nursing Severity Scale scores compared with the activity group . Both MSSE and activity groups showed an improvement during the intervention in the Cohen-Mansfield Agitation Inventory aggressive behavior factor and total score , with no significant differences between groups . The MSSE may have better effects on neuropsychiatric symptoms and dementia severity in comparison with one-to-one activity sessions in patients with severe dementia OBJECTIVE To investigate the feasibility and effectiveness of Sonas , a group intervention involving multisensory stimulation , reminiscence , and light physical activity . METHODS A total of 39 participants with moderate to severe dementia were r and omized to receive either 14 sessions of Sonas or treatment as usual . Measures such as quality of life ( QoL ) , communication , depression , anxiety , and behavioral disturbance were administered at baseline and follow-up . RESULTS No statistically significant results were found . However , participant attendance to sessions was good ( mean = 12.4 sessions of 14 offered ) . CONCLUSIONS Sonas sessions did not lead to improvements in QoL and behavioral and psychological symptoms of dementia |
12,107 | 30,999,928 | This meta- analysis suggests that SCT may contribute to the improvement of LVEF , as well as the reduction of the NYHA class , CCS grade , and LVESV .
In addition , SCT does not affect mortality | Stem cell transplantation ( SCT ) has become a promising way to treat ischemic heart failure ( IHF ) .
We performed a large-scale meta- analysis of r and omized clinical trials to investigate the efficacy and safety of SCT in IHF patients . | Background —This study evaluated the hypothesis that transendocardial injections of autologous mononuclear bone marrow cells in patients with end-stage ischemic heart disease could safely promote neovascularization and improve perfusion and myocardial contractility . Methods and Results —Twenty-one patients were enrolled in this prospect i ve , nonr and omized , open-label study ( first 14 patients , treatment ; last 7 patients , control ) . Baseline evaluations included complete clinical and laboratory evaluations , exercise stress ( ramp treadmill ) , 2D Doppler echocardiogram , single-photon emission computed tomography perfusion scan , and 24-hour Holter monitoring . Bone marrow mononuclear cells were harvested , isolated , washed , and resuspended in saline for injection by NOGA catheter ( 15 injections of 0.2 cc ) . Electromechanical mapping was used to identify viable myocardium ( unipolar voltage ≥6.9 mV ) for treatment . Treated and control patients underwent 2-month noninvasive follow-up , and treated patients alone underwent a 4-month invasive follow-up according to st and ard protocol s and with the same procedures used as at baseline . Patient population demographics and exercise test variables did not differ significantly between the treatment and control groups ; only serum creatinine and brain natriuretic peptide levels varied in laboratory evaluations at follow-up , being relatively higher in control patients . At 2 months , there was a significant reduction in total reversible defect and improvement in global left ventricular function within the treatment group and between the treatment and control groups ( P = 0.02 ) on quantitative single-photon emission computed tomography analysis . At 4 months , there was improvement in ejection fraction from a baseline of 20 % to 29 % ( P = 0.003 ) and a reduction in end-systolic volume ( P = 0.03 ) in the treated patients . Electromechanical mapping revealed significant mechanical improvement of the injected segments ( P < 0.0005 ) at 4 months after treatment . Conclusions —Thus , the present study demonstrates the relative safety of intramyocardial injections of bone marrow – derived stem cells in humans with severe heart failure and the potential for improving myocardial blood flow with associated enhancement of regional and global left ventricular function AIMS Despite accumulated evidence that intracoronary bone marrow cell ( BMC ) therapy may be beneficial in acute myocardial infa rct ion , there are only limited data available on the effectiveness of BMC 's in chronic heart failure . The aim of this study was to quantitatively investigate ventricular haemodynamics , geometry , and contractility as well as the long-term clinical outcome of BMC treated patients with reduced left ventricular ejection fraction ( LVEF ) due to chronic ischaemic cardiomyopathy . METHODS AND RESULTS Patients with chronic heart failure ( n = 391 LVEF < or=35 % ) due to ischaemic cardiomyopathy were enrolled in the present study . Of these , 191 patients ( mean NYHA class 3.22 ) underwent intracoronary BMC therapy . The control group ( mean NYHA class 3.06 ) consisted of 200 patients with comparable LVEF . Assessment s of haemodynamics at rest and exercise , quantitative ventriculography , spiroergometry , 24 h Holter ECG , late potentials , and heart rate variability were analysed . Over 3 months to 5 years after intracoronary BMC therapy there was a significant improvement in haemodynamics ( e.g. LVEF , cardiac index ) , exercise capacity , oxygen uptake , and LV contractility . Importantly , there was a significant decrease in long-term mortality in the BMC treated patients compared with the control group . CONCLUSION Intracoronary BMC therapy improves ventricular performance , quality of life and survival in patients with heart failure . These effects were present when BMC were administered in addition to st and ard therapeutic regimes . No side effects were observed OBJECTIVES This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure . BACKGROUND In pre- clinical heart failure models , cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling . METHODS The C-CURE ( Cardiopoietic stem Cell therapy in heart failURE ) trial , a prospect i ve , multicenter , r and omized trial , was conducted in patients with heart failure of ischemic origin who received st and ard of care or st and ard of care plus lineage-specified stem cells . In the cell therapy arm , bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail . Derived cardiopoietic stem cells , meeting release criteria under Good Manufacturing Practice , were delivered by endomyocardial injections guided by left ventricular electromechanical mapping . Data acquisition and analysis were performed in blinded fashion . The primary endpoint was feasibility/safety at 2-year follow-up . Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy . RESULTS Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75 % and delivery without complications in 100 % of cases . There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy . Left ventricular ejection fraction was improved by cell therapy ( from 27.5 ± 1.0 % to 34.5 ± 1.1 % ) versus st and ard of care alone ( from 27.8 ± 2.0 % to 28.0 ± 1.8 % , p < 0.0001 ) and was associated with a reduction in left ventricular end-systolic volume ( -24.8 ± 3.0 ml vs. -8.8 ± 3.9 ml , p < 0.001 ) . Cell therapy also improved the 6-min walk distance ( + 62 ± 18 m vs. -15 ± 20 m , p < 0.01 ) and provided a superior composite clinical score encompassing cardiac parameters in t and em with New York Heart Association functional class , quality of life , physical performance , hospitalization , and event-free survival . CONCLUSIONS The C-CURE trial implements the paradigm of lineage guidance in cell therapy . Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure , meriting definitive clinical evaluation . ( C-Cure Clinical Trial ; NCT00810238 ) BACKGROUND Autologous adult stem cell transplantation has been touted as the latest tool in regenerative medical therapy . Its potential for use in cardiovascular disease has only recently been recognized . A r and omized study was conducted with a novel epicardial technique to deploy stem cells as an adjuvant to conventional revascularization therapy in patients with congestive heart failure . METHODS After institutional review board and government approval , adult autologous stem cell transplantation ( CD34 + ) was performed in patients with ischemic cardiomyopathy and an ejection fraction of less than 35 % who were scheduled for primary off-pump coronary artery bypass grafting . Preoperatively , the patients underwent echocardiography , stress thallium imaging single photon emission computed tomography , and cardiac catheterization to identify ischemic regions of the heart and to guide in the selection of stem cell injection sites . The patients were prospect ively r and omized before the operative therapy was performed . Patient follow-up was 1 , 3 , and 6 months with echocardiography , single photon emission computed tomography , and angiography . RESULTS There were 20 patients enrolled in the study . Ten patients had successful subepicardial transplantation of autologous stem cells into ischemic myocardium . The other 10 patients , the control group , only had off-pump coronary artery bypass grafting . There were 8 male and 2 female subjects in each group . The median number of grafts performed was 1 in both groups . On angiographic follow-up , all grafts were patent at 6 months . The ejection fractions of the off-pump coronary artery bypass grafting group versus the off-pump coronary artery bypass grafting plus stem cell transplantation group were as follows : preoperative , 30.7 % + /- 2.5 % versus 29.4 % + /- 3.6 % ; 1 month , 36.4 % + /- 2.6 % versus 42.1 % + /- 3.5 % ; 3 months , 36.5 % + /- 3.0 % versus 45.5 % + /- 2.2 % ; and 6 months , 37.2 % + /- 3.4 % versus 46.1 % + /- 1.9 % ( P < .001 ) . There were no perioperative arrhythmias or neurologic or ischemic myocardial events in either group . CONCLUSIONS Autologous stem cell transplantation led to significant improvement in cardiac function in patients undergoing off-pump coronary artery bypass grafting for ischemic cardiomyopathy . Further investigation is required to quantify the optimal timing and specific cellular effects of the therapy OBJECTIVES The graft of stem cells to treat ischemic cardiomyopathy is popular in many clinical trials . The aim of this study was to evaluate the effectiveness of isolated coronary artery bypass graft combined with bone marrow mononuclear cells ( BMMNC ) delivered through graft vessels to improve left ventricular function of patients with previous myocardial infa rct ion and chronic heart failure using echocardiography . METHODS Forty-two patients with previous myocardial infa rct ion and chronic heart failure were r and omly allocated to one of the two groups : CABG only ( 18 in CABG group ) , or CABG with BMMNC transplantation ( 24 in CABG + BMMNC group ) . Echocardiographic parameters of systolic function were measured on B-mode imaging , tissue Doppler imaging ( TDI ) , two-dimensional ( 2D ) strain imaging , and 8 parameters were measured totally . Echocardiographic parameters of diastolic function were measured on pulsed-wave Doppler imaging , TDI , and 2D strain rate imaging ; 17 parameters were measured totally . RESULTS Postoperative left ventricular ejection fraction ( LVEF ) versus preoperative LVEF were 49.083 ± 1.914 % versus 36.042 ± 1.185 % ( P < 0.05 ) in CABG + BMMMNC group and 41.389 ± 2.210 % versus 34.667 ± 1.369 % ( P < 0.05 ) in CABG group , global longitudinal strain were -12.542 ± 0.512 % versus -7.083 ± 0.583 % ( P < 0.05 ) in CABG + BMMMNC group and -9.278 ± 0.591 % versus -7.000 ± 0.673 % ( P < 0.05 ) in CABG group , mLsr1 were -0.108 ± 0.018/sec versus -0.039 ± 0.017/sec ( P < 0.05 ) in CABG+BMMMNC group and -0.048 ± 0.021/sec versus 0.004 ± 0.020/sec ( P < 0.05 ) in CABG group , mLsr2 were -0.055 ± 0.013/sec versus -0.009 ± 0.015/sec ( P < 0.05 ) in CABG + BMMMNC group and 0.004 ± 0.015/sec versus 0.024 ± 0.017/sec ( P < 0.05 ) in CABG group , and Aa1 were 7.303 ± 0.479 cm/sec versus 5.131 ± 0.381 cm/sec ( P < 0.05 ) in CABG + BMMMNC group and 7.908 ± 0.553 cm/sec versus 6.764 ± 0.440 cm/sec ( P < 0.05 ) in CABG group . Parameters above were significantly improved postoperatively in both groups . The degree of the improvement was significantly different between the two groups with the CABG + BMMNC group improved more versus the group of CABG only ( P < 0.05 ) . CONCLUSIONS The improvement of left ventricular function in CABG + BMMNC group is better than CABG group . 2D strain and strain rate imaging is a more sensitive tool to evaluate left ventricular function OBJECTIVES This study aim ed at examining the efficacy of bone marrow mononuclear cell ( BMMNC ) delivery through graft vessel for patients with a previous myocardial infa rct ion ( MI ) and chronic heart failure during coronary artery bypass graft ( CABG ) . BACKGROUND Little evidence exists supporting the practice of BMMNC delivery through graft vessel for patients with a previous MI and chronic heart failure during CABG . METHODS From November 2006 to June 2009 , a r and omized , placebo-controlled trial was conducted to test the efficacy and safety of CABG for multivessel coronary artery disease combined with autologous BMMNCs in patients with congestive heart failure due to severe ischemic cardiomyopathy . Sixty-five patients were recruited , and 60 patients remained in the final trial and were r and omized to a CABG + BMMNC group ( n = 31 ) and a placebo-control group ( i.e. , CABG-only group , n = 29 ) . All patients discharged received a 6-month follow-up . Changes in left ventricular ejection fraction from baseline to 6-month follow-up , as examined by magnetic resonance imaging , were of primary interest . RESULTS The overall baseline age was 59.5 ± 9.2 years , and 6.7 % were women . After a 6-month follow-up , compared with the placebo-control group , the CABG + BMMNC group had significant changes in left ventricular ejection fraction ( p = 0.029 ) , left ventricular end-systolic volume index ( p = 0.017 ) , and wall motion index score ( p = 0.011 ) . Also , the changes in the distance on the 6-min walking test as well as B-type natriuretic peptide were significantly greater in the CABG + BMMNC group than in the control group . CONCLUSIONS In summary , patients with a previous MI and chronic heart failure could potentially benefit from isolated CABG ( i.e. , those who received CABG only ) combined with BMMNCs delivered through a graft vessel . ( Stem Cell Therapy to Improve Myocardial Function in Patients Undergoing Coronary Artery Bypass Grafting [ CABG ] ; NCT00395811 ) Background — Phase I clinical studies have demonstrated the feasibility of implanting autologous skeletal myoblasts in postinfa rct ion scars . However , they have failed to determine whether this procedure was functionally effective and arrhythmogenic . Methods and Results — This multicenter , r and omized , placebo-controlled , double-blind study included patients with left ventricular ( LV ) dysfunction ( ejection fraction ≤35 % ) , myocardial infa rct ion , and indication for coronary surgery . Each patient received either cells grown from a skeletal muscle biopsy or a placebo solution injected in and around the scar . All patients received an implantable cardioverter-defibrillator . The primary efficacy end points were the 6-month changes in global and regional LV function assessed by echocardiography . The safety end points comprised a composite index of major cardiac adverse events and ventricular arrhythmias . Ninety-seven patients received myoblasts ( 400 or 800 million ; n=33 and n=34 , respectively ) or the placebo ( n=30 ) . Myoblast transfer did not improve regional or global LV function beyond that seen in control patients . The absolute change in ejection fraction ( median [ interquartile range ] ) between 6 months and baseline was 4.4 % ( 0.2 ; 7.3 ) , 3.4 % ( −0.3 ; 12.4 ) , and 5.2 % ( −4.4 ; 11.0 ) in the placebo , low-dose , and high-dose groups , respectively ( P=0.95 ) . However , the high-dose cell group demonstrated a significant decrease in LV volumes compared with the placebo group . Despite a higher number of arrhythmic events in the myoblast-treated patients , the 6-month rates of major cardiac adverse events and of ventricular arrhythmias did not differ significantly between the pooled treatment and placebo groups . Conclusions — Myoblast injections combined with coronary surgery in patients with depressed LV function failed to improve echocardiographic heart function . The increased number of early postoperative arrhythmic events after myoblast transplantation , as well as the capability of high-dose injections to revert LV remodeling , warrants further investigation 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 Intramyocardial transplantation of autologous bone marrow mononuclear cells ( BMMC ) is believed to be a promising method for the treatment of patients with chronic ischemic heart disease . The aim of this study was to evaluate long-term results of intramyocardial bone marrow cell transplantation in patients with severe ischemic heart failure . One hundred nine patients with chronic myocardial infa rct ion and end-stage chronic heart failure were r and omized into two groups : 55 patients received intramyocardial BMMC injection and 54 received optimal medical therapy . The NOGA system ( Biosense-Webster ) was used to administer 41 ± 16 × 106 BMMC into the border zone of myocardial infa rct ion . None of the patients developed periprocedural complications following BMMC injections . The injections led to improvement of CCS class ( 3.1 ± 0.4 to 1.6 ± 0.6 after 6 months and 1.6 ± 0.4 after 12 months ; p = 0.001 ) and NYHA functional class ( 3.3 ± 0.2 to 2.3 ± 0.2 after 6 months and 2.5 ± 0.1 after 12 months ; p = 0.006 ) . Left ventricular ejection fraction increased significantly in the BMMC group ( 27.8 ± 3.4 % vs 32.3 ± 4.1 % ; p = 0.04 ) while it tended to decrease in the control group ( 26.8 ± 3.8 % to 25.2 ± 4.1 % ; p = 0.61 ) . Summed rest score improved in the BMMC group after 12 months ( 30.2 ± 5.6 to 27.8 ± 5.1 ; p = 0.032 ) . The improvement of stress score was more noticeable ( 34.5 ± 5.4 to 28.1 ± 5.2 ; p = 0.016 ) . Neither stress nor rest score changed in patients numbers on medical therapy . In BMMC group 6 ( 10.9 % ) patients died at 12-month follow-up compared with 21 ( 38.9 % ) in control group ( log-rank test , p = 0.0007 ) . Intramyocardial bone marrow cell transplantation to patients with ischemic heart failure is safe and improved survival , clinical symptoms , and has beneficial effect on LV RATIONALE Allogeneic mesenchymal precursor cells ( MPCs ) have been effective in large animal models of ischemic and nonischemic heart failure ( HF ) . OBJECTIVE To evaluate the feasibility and safety of 3 doses ( 25 , 75 , or 150 million cells ) of immunoselected allogeneic MPCs in chronic HF patients in a phase 2 trial . METHODS AND RESULTS We sequentially allocated 60 patients to a dosing cohort ( 20 per dose group ) and r and omized them to transendocardial MPC injections ( n=15 ) or mock procedures ( n=5 ) . The primary objective was safety , including antibody testing . Secondary efficacy end points included major adverse cardiac events ( MACE ; cardiac death , myocardial infa rct ion , or revascularization ) , left ventricular imaging , and other clinical -event surrogates . Safety and MACE were evaluated for up to 3 years . MPC injections were feasible and safe . Adverse events were similar across groups . No clinical ly symptomatic immune responses were noted . MACE was seen in 15 patients : 10 of 45 ( 22 % ) MPC-treated and 5 of 15 ( 33 % ) control patients . We found no differences between MPC-treated and control patients in survival probability , MACE-free probability , and all-cause mortality . We conducted a post hoc analysis of HF-related MACE ( HF hospitalization , successfully resuscitated cardiac death , or cardiac death ) and events were significantly reduced in the 150 million MPC group ( 0/15 ) versus control ( 5/15 ; 33 % ) , 25 million MPC group ( 3/15 ; 20 % ) , and 75 million MPC group ( 6/15 ; 40 % ) ; the 150 million MPC group differed significantly from all groups according to Kaplan-Meier statistics > 3 years ( P=0.025 for 150 million MPC group versus control ) . CONCLUSIONS Transendocardial injections of allogeneic MPCs were feasible and safe in chronic HF patients . High-dose allogeneic MPCs may provide benefits in this population BACKGROUND Ixmyelocel-T is an exp and ed , multicellular therapy produced from a patient 's own bone marrow by selectively exp and ing two key types of bone marrow mononuclear cells : CD90 + mesenchymal stem cells and CD45 + CD14 + auto-fluorescent+ activated macrophages . Early phase clinical trials suggest that intramyocardial delivery of ixmyelocel-T might improve clinical , functional , symptomatic , and quality -of-life outcomes in patients with heart failure due to ischaemic dilated cardiomyopathy . We aim ed to assess the safety and efficacy of catheter-based transendocardial injection of ixmyelocel-T cell therapy in patients with heart failure and reduced ejection fractions . METHODS In this r and omised , double-blind , placebo-controlled phase 2B trial ( ixCELL-DCM ) , patients from 31 sites in North America with New York Heart Association class III or IV symptomatic heart failure due to ischaemic dilated cardiomyopathy , who had left ventricular ejection fraction 35 % or less , an automatic implantable cardioverter defibrillator , and who were ineligible for revascularisation procedures were r and omly assigned ( 1:1 ) to receive ixmyelocel-T or placebo at the time of bone marrow aspiration and followed for 12 months . R and omisation was done through an interactive ( voice/web ) response system . The pharmacist , treating physician , and coordinator at each site were unblinded , but the the follow-up team was completely blinded . The primary endpoint was a composite of all-cause death , cardiovascular admission to hospital , and unplanned clinic visits to treat acute decompensated heart failure based on the blinded adjudication of an independent clinical endpoint committee . Primary efficacy endpoint analyses and safety analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT01670981 . FINDINGS Between April 2 , 2013 , and Jan 28 , 2015 , 126 participants were r and omly assigned to receive either ixmyelocel-T ( n=66 ) or placebo ( n=60 ) . 114 ( 90 % ) patients comprised the modified intention-to-treat population and 109 ( 87 % ) patients were included in the per- protocol primary efficacy analysis ( 58 in the ixmyelocel-T group and 51 in the placebo group ) . The primary efficacy endpoint was observed in 47 patients : 50 events in 25 ( 49 % ) of 51 patients in the placebo group and 38 events in 22 ( 38 % ) of 58 patients in the ixmyelocel-T group , which represents a 37 % reduction in cardiac events compared with placebo ( risk ratio 0·63 [ 95 % CI 0·42 - 0·97 ] ; p=0·0344 ) . 41 ( 75 % ) of 51 participants in the placebo group had serious adverse events versus 31 ( 53 % ) of 58 in the ixmyelocel-T group ( p=0·0197 ) . INTERPRETATION To the best of our knowledge , ixCELL-DCM is the largest cell therapy study done in patients with heart failure so far . The transendocardial delivery of ixmyelocel-T in patients with heart failure and reduced ejection fraction due to ischaemic dilated cardiomyopathy result ed in a significant reduction in adjudicated clinical cardiac events compared with placebo leading to improved patient outcomes . FUNDING Vericel Corporation BACKGROUND Autologous bone marrow mononuclear cell ( ABMMNC ) therapy has shown promise in patients with heart failure ( HF ) . Cell function analysis may be important in interpreting trial results . METHODS In this prospect i ve study , we evaluated the safety and efficacy of the transendocardial delivery of ABMMNCs in no-option patients with chronic HF . Efficacy was assessed by maximal myocardial oxygen consumption , single photon emission computed tomography , 2-dimensional echocardiography , and quality -of-life assessment ( Minnesota Living with Heart Failure and Short Form 36 ) . We also characterized patients ' bone marrow cells by flow cytometry , colony-forming unit , and proliferative assays . RESULTS Cell-treated ( n = 20 ) and control patients ( n = 10 ) were similar at baseline . The procedure was safe ; adverse events were similar in both groups . Canadian Cardiovascular Society angina score improved significantly ( P = .001 ) in cell-treated patients , but function was not affected . Quality -of-life scores improved significantly at 6 months ( P = .009 Minnesota Living with Heart Failure and P = .002 physical component of Short Form 36 ) over baseline in cell-treated but not control patients . Single photon emission computed tomography data suggested a trend toward improved perfusion in cell-treated patients . The proportion of fixed defects significantly increased in control ( P = .02 ) but not in treated patients ( P = .16 ) . Function of patients ' bone marrow mononuclear cells was severely impaired . Stratifying cell results by age showed that younger patients ( ≤60 years ) had significantly more mesenchymal progenitor cells ( colony-forming unit fibroblasts ) than patients > 60 years ( 20.16 ± 14.6 vs 10.92 ± 7.8 , P = .04 ) . Furthermore , cell-treated younger patients had significantly improved maximal myocardial oxygen consumption ( 15 ± 5.8 , 18.6 ± 2.7 , and 17 ± 3.7 mL/kg per minute at baseline , 3 months , and 6 months , respectively ) compared with similarly aged control patients ( 14.3 ± 2.5 , 13.7 ± 3.7 , and 14.6 ± 4.7 mL/kg per minute , P = .04 ) . CONCLUSIONS ABMMNC therapy is safe and improves symptoms , quality of life , and possibly perfusion in patients with chronic HF AIM This study presents an interim safety and feasibility analysis of the REGENERATE-IHD r and omized controlled trial , which is examining the safety and efficacy of three different delivery routes of bone marrow-derived stem cells ( BMSCs ) in patients with ischemic heart failure . METHODS & RESULTS The first 58 patients recruited to the REGENERATE-IHD study are included in this interim analysis ( pilot ) . Symptomatic patients with ischemic heart failure were r and omized to receive subcutaneous granulocyte colony-stimulating factor or saline injections only ; or subcutaneous granulocyte colony-stimulating factor injections followed by intracoronary or intramyocardial injections of BMSCs or serum ( control ) . No significant differences were found in terms of safety and feasibility between the different delivery routes , with no significant difference in procedural complications or major adverse cardiac events . There was a signal towards improved heart failure symptoms in the patients treated with intramyocardial injection of mobilized BMSCs . CONCLUSION Peripheral mobilization of BMSCs with or without subsequent direct myocardial delivery appears safe and feasible in patients with chronic ischemic heart failure BACKGROUND The optimal type of stem cell for use in patients with ischemic heart disease has not been determined . A primitive population of bone marrow-derived hematopoietic cells has been isolated by the presence of the enzyme aldehyde dehydrogenase and comprises a multilineage mix of stem and progenitor cells . Aldehyde dehydrogenase-bright ( ALDH(br ) ) cells have shown promise in promoting angiogenesis and providing perfusion benefits in pre clinical ischemia studies . We hypothesize that ALDH(br ) cells may be beneficial in treating ischemic heart disease and thus conducted the first r and omized , controlled , double-blind study to assess the safety of the transendocardial injection of autologous ALDH(br ) cells isolated from the bone marrow in patients with advanced ischemic heart failure . METHODS Aldehyde dehydrogenase-bright cells were isolated from patients ' bone marrow on the basis of the expression of a functional ( aldehyde dehydrogenase ) marker . We enrolled 20 patients ( treatment , n = 10 ; control , n = 10 ) . Safety ( primary end point ) and efficacy ( secondary end point ) were assessed at 6 months . RESULTS No major adverse cardiovascular or cerebrovascular events occurred in ALDH(br)-treated patients in the periprocedural period ( up to 1 month ) ; electromechanical mapping-related ventricular tachycardia ( n = 2 ) and fibrillation ( n = 1 ) occurred in control patients . Aldehyde dehydrogenase-bright-treated patients showed a significant decrease in left ventricular end-systolic volume at 6 months ( P = .04 ) and a trend toward improved maximal oxygen consumption . The single photon emission computed tomography delta analysis showed a trend toward significant improvement in reversibility in cell-treated patients ( P = .053 ) . CONCLUSIONS We provide preliminary evidence that treatment with the novel cell population , ALDH(br ) cells , is safe and may provide perfusion and functional benefits in patients with chronic myocardial ischemia BACKGROUND Mononuclear bone marrow cell ( MN- BMC ) transplantation has great clinical potential to promote myocardiogenesis and angiogenesis . This r and omized study was design ed to assess the feasibility and safety of MN- BMC transplantation during coronary artery bypass grafting ( CABG ) in patients with ischemic heart failure . METHODS Thirty-six patients were prospect ively enrolled and r and omized to a MN- BMC group ( n = 18 ) and a control group ( n = 18 ) . A mean number of 6.59 x 10(8 ) + /- 5.12 x 10(8 ) MN- BMC were injected into the infa rct ed and marginal areas during CABG in the MN- BMC group . The patients in the control group underwent CABG alone . All patients were followed up to 6 months . RESULTS There was one death in the MN- BMC group and no death in the control group . Two patients developed ventricular arrhythmia in the MN- BMC group . Compared with baseline and the control group , therapeutic effects of MN- BMC transplantation were observed over time . Heart function ( New York Heart Association ) was significantly improved and angina pectoris was alleviated in the MN- BMC group . Left ventricular ejection fraction in the MN- BMC group was greater than the control group . The thickness and motion velocity of the infa rct ed wall were significantly increased in the MN- BMC group . More pronounced perfusion improvements of ischemic regions and LV were observed in the MN- BMC group . There was one late death in the MN- BMC group . No procedure-related complications occurred . CONCLUSIONS MN- BMC transplantation improves cardiac function and regional perfusion in ischemic heart failure patients during CABG . A large cohort with long-term follow-up is needed to further evaluate the safety of MN- BMC transplantation AIMS Regenerative treatment with mesenchymal stromal cells ( MSCs ) has been promising in patients with ischaemic heart failure but needs confirmation in larger r and omized trials . We aim ed to study effects of intra-myocardial autologous bone marrow-derived MSC treatment in patients with severe ischaemic heart failure . METHODS AND RESULTS The MSC-HF trial is a r and omized , double-blind , placebo-controlled trial . Patients were r and omized 2 : 1 to intra-myocardial injections of MSC or placebo , respectively . The primary endpoint was change in left ventricular end-systolic volume ( LVESV ) , measured by magnetic resonance imaging or computed tomography at 6 months follow-up . Sixty patients aged 30 - 80 years with severe ischaemic heart failure , New York Heart Association ( NYHA ) classes II-III , left ventricular ejection fraction ( LVEF ) < 45 % and no further treatment options were r and omized . Fifty-five patients completed the 6-month follow-up ( 37 MSCs vs. 18 placebo ) . At 6 months , LVESV was reduced in the MSC group : -7.6 ( 95 % CI -11.8 to -3.4 ) mL ( P = 0.001 ) , and increased in the placebo group : 5.4 ( 95 % CI -0.4 to 11.2 ) mL ( P = 0.07 ) . The difference between groups was 13.0 ( 95 % CI 5.9 - 20.1 ) mL ( P = 0.001 ) . Compared with placebo , there were also significant improvements in LVEF of 6.2 % ( P<0.0001 ) , stroke volume of 18.4 mL ( P < 0.0001 ) , and myocardial mass of 5.7 g ( P = 0.001 ) . No differences were found in NYHA class , 6-min walking test and Kansas City cardiomyopathy question naire . No side effects were identified . CONCLUSION Intra-myocardial injections of autologous culture exp and ed MSCs were safe and improved myocardial function in patients with severe ischaemic heart failure . STUDY REGISTRATION NUMBER NCT00644410 ( Clinical Trials.gov ) OBJECTIVES The aim of this study was to test safety and feasibility of myoblast transplantation with the Biosense-NOGA ( Diamond Bar , California ) 3-dimensional-guided endomyocardial delivery system . BACKGROUND Previous Phase-1 trials showed feasibility of epicardial injection of myoblasts . However , catheter-based delivery has several advantages : it can be applied on high-risk patients , the procedure can be repeated , and it is associated with less morbidity and mortality . METHODS Twenty-three subjects , with previous myocardial infa rct ion and heart failure , New York Heart Association ( NYHA ) functional class II to IV , were enrolled , 11 control and 12 treatment subjects . To assess safety , physical exam , electrocardiogram , continuous rhythm monitoring , quality of life assessment s , and heart function were evaluated at baseline and follow-up until 1 year . RESULTS There was favorable safety : no difference between groups in arrhythmias , and no deaths . Treated subjects showed sustained improvements in NYHA and Minnesota Living with Heart Failure Question naire ( MLHFQ ) compared with control subjects ( NYHA , -1.0 point in treatment vs. + 0.3 point in control group , p < 0.0004 ; MLHFQ , -14 point in treatment vs. + 1 point in the control group , p = 0.004 ) . Blinded core laboratory echocardiography evaluations showed sustained reductions in the treatment versus control in end diastolic diameter ( -0.03 cm vs. + 0.05 cm , p = 0.07 ) and end systolic diameter ( -0.05 cm vs. + 0.1 cm , p = 0.07 ) . Finally , NOGA voltage mapping demonstrated improved voltage measurements ( + 1.0 mV , p = 0.008 ) . CONCLUSIONS This trial of myoblast transplantation via catheter into heart failure patients demonstrated safety and feasibility . Treated patients showed improvement in NYHA , MLHFQ , ventricular viability , and evidence of reverse ventricular remodeling . These data demonstrate positive safety outcomes and warrant initiation of larger phase 2 , double-blind , placebo-controlled clinical trials UNLABELLED Cell therapy is an evolving option for patients with end-stage heart failure and ongoing symptoms despite optimal medical therapy . Our goal was to evaluate retro grade bone marrow cell delivery in patients with either ischemic heart failure ( IHF ) or nonischemic heart failure ( NIHF ) . This was a prospect i ve r and omized , multicenter , open-label study of the safety and feasibility of bone marrow aspirate concentrate ( BMAC ) infused retro grade into the coronary sinus . Sixty patients were stratified by IHF and NIHF and r and omized to receive either BMAC infusion or control ( st and ard heart failure care ) in a 4:1 ratio . Accordingly , 24 subjects were r and omized to the ischemic BMAC group and 6 to the ischemic control group . Similarly , 24 subjects were r and omized to the nonischemic BMAC group and 6 to the nonischemic control group . All 60 patients were successfully enrolled in the study . The treatment groups received BMAC infusion without complications . The left ventricular ejection fraction in the patients receiving BMAC demonstrated significant improvement compared with baseline , from 25.1 % at screening to 31.1 % at 12 months ( p=.007 ) in the NIHF group and from 26.3 % to 31.1 % in the IHF group ( p=.035 ) . The end-systolic diameter decreased significantly in the nonischemic BMAC group from 55.6 to 50.9 mm ( p=.020 ) . Retro grade BMAC delivery is safe . All patients receiving BMAC experienced improvements in left ventricular ejection fraction , but only those with NIHF showed improvements in left ventricular end-systolic diameter and B-type natriuretic peptide . These results provide the basis for a larger clinical trial in HF patients . SIGNIFICANCE This work is the first prospect i ve r and omized clinical trial using high-dose cell therapy delivered via a retro grade coronary sinus infusion in patients with heart failure . This was a multinational , multicenter study , and it is novel , translatable , and scalable . On the basis of this trial and the safety of retro grade coronary sinus infusion , there are three other trials under way using this route of delivery |
12,108 | 19,588,427 | Adverse events were uncommon , and not significantly different from placebo .
AUTHORS ' CONCLUSIONS Flurbiprofen at doses of 50 mg and 100 mg is an effective analgesic in moderate to severe acute postoperative pain .
The NNT for at least 50 % pain relief is similar to that of commonly used NSAIDs such as ibuprofen and naproxen at usual doses .
Use of rescue medication indicates a duration of action exceeding 6 hours | BACKGROUND Flurbiprofen is a non-selective non-steroidal anti-inflammatory drug ( NSAID ) , related to ibuprofen and naproxen , used to treat acute and chronic painful conditions .
There is no systematic review of its use in acute postoperative pain .
OBJECTIVES To assess efficacy , duration of action , and associated adverse events of single dose oral flurbiprofen in acute postoperative pain in adults . | Following the demonstration that increased prostagl and in F2 alpha production causes pain similar to dysmenorrhea , and the finding that prostagl and in synthetase inhibitors are capable of relieving menstrual pain , the early theory of uterine ischemia has once again gained support as the most likely explanation for this condition . In a double-blind , placebo-controlled , crossover study , 30 of 43 women with moderate to severe dysmenorrhea who completed the trial preferred flurbiprofen ( Ansaid , Upjohn ) , a potent new analgesic/anti-inflammatory agent ( 50 mg four times daily ) , to aspirin ( 650 mg four times daily ) and placebo . Flurbiprofen was also rated superior to aspirin and placebo in the degree of pain relief . An algorithm for the diagnosis and treatment of 90 percent of women with primary dysmenorrhea is presented The purpose of the present investigation was to compare the analgesic efficacy of flurbiprofen , a nonsteroidal anti-inflammatory drug , which is a phenyl propionic acid derivative , with acetaminophen and placebo in 63 adult out patients with moderate to severe dental pain following periodontal surgery . After surgery was completed under local anesthesia , the patients received under double-blind conditions an envelope containing four tablets of either flurbiprofen 100 mg , acetaminophen 500 mg , or placebo and they were instructed to take one tablet every 6 hours when postoperative pain reached moderate to severe intensity . To determine analgesic efficacy and patients recorded pain intensity on a scale of 0 to 3 . Patients were allowed to remedicate after 1 hour if pain was not reduced . Flurbiprofen was shown to possess an adequate analgesic effect superior to either placebo ( P less than 0.005 ) or acetaminophen ( P less than 0.01 ) in the parameters studied . Our results seem to further support earlier data obtained with the drug in dental patients with postoperative pain after the surgical removal of impacted third molars ; therefore , it is concluded that flurbiprofen used as directed is a new alternative for the proper treatment of pain following periodontal surgery 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 & NA ; There is uncertainty over whether the patient group in which acute pain studies are conducted ( pain model ) has any influence on the estimate of analgesic efficacy . Data from four recently up date d systematic review s of aspirin 600/650 mg , paracetamol 600/650 mg , paracetamol 1000 mg and ibuprofen 400 mg were used to investigate the influence of pain model . Area under the pain relief versus time curve equivalent to at least 50 % maximum pain relief over 6 h was used as the outcome measure . Event rates with treatment and placebo , and relative benefit ( RB ) and number needed to treat ( NNT ) were used as outputs from the meta‐analyses . The event rate with placebo was systematic ally statistically lower for dental than postsurgical pain for all four treatments . Event rates with analgesics , RB and NNT were infrequently different between the pain models . Systematic difference in the estimate of analgesic efficacy between dental and postsurgical pain models remains unproven , and , on balance , no major difference is likely Flurbiprofen ( Ansaid , Upjohn ) , a potent new analgesic and anti-inflammatory agent , was compared with phenylbutazone in 90 patients with ankylosing spondylitis . In this double-blind , r and omized , 26-week study , a total daily dose of 200 mg of flurbiprofen , administered three times daily , was as effective as 300 mg of phenylbutazone in controlling the pain and other symptoms of ankylosing spondylitis . In some patients , symptoms were adequately controlled by 150 mg of flurbiprofen per day , administered twice daily . There were no statistically significant differences between flurbiprofen and phenylbutazone in the investigators ' and patients ' assessment s of improvement at all key follow-up periods . In addition , there were no consistently significant differences between drugs in the efficacy pain scales and quantitative measurements studied . Flurbiprofen was well tolerated in doses of up to 300 mg per day , and no clinical ly significant laboratory abnormalities were detected . Flurbiprofen appears to be an excellent alternative to phenylbutazone in the management of patients with ankylosing spondylitis 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 This single-dose , double-blind , r and omized , placebo-controlled study compared the efficacy of 50 mg of oral flurbiprofen ( Ansaid , Upjohn ) , 10 mg of intramuscular morphine sulfate , and placebo in 92 patients with moderate to severe postoperative gynecologic pain . According to pain intensity , pain relief , and pain intensity difference scores , the morphine-treated patients experienced significantly more pain reduction than the other patients by the first hour after treatment . The flurbiprofen group obtained the same level of significant pain relief as the morphine group by two hours after dosing , but relief persisted longer than in the morphine-treated patients . Evaluation of other efficacy variables revealed similar levels of significant pain reduction in both the flurbiprofen and morphine groups compared with the placebo group . Flurbiprofen was well tolerated and led to fewer side effects than either morphine or placebo & 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 The analgesic efficacy of flurbiprofen 25 mg and 50 mg compared with aspirin 650 mg and placebo ( lactose ) was evaluated . Subjects were 164 dental out patients undergoing the surgical removal of impacted teeth . Each subject received a single dose of study medication and was evaluated hourly for six hours . Aspirin was superior to placebo in all measures of analgesic efficacy , and both dosages of flurbiprofen were superior to aspirin In a series of three studies involving dental out patients undergoing removal of impacted third molars , preoperative and postoperative administration of flurbiprofen ( Ansaid , Upjohn ) led to superior pain relief when compared with acetaminophen alone or in combination with oxycodone . Patient preference and global evaluations clearly favored flurbiprofen . Side effects were mild and generally more common in patients receiving the opiate/mild analgesic combination . In two additional studies , flurbiprofen and etidocaine , a long-acting local anesthetic , also result ed in significantly less postoperative pain than a combination of acetaminophen/oxycodone and lidocaine ; 67 percent of patients in the flurbiprofen plus etidocaine group reported no or only slight pain during the entire observation period . The greater analgesic efficacy of flurbiprofen appears to represent a genuine therapeutic advantage , since it is not achieved at the expense of greater side effects Pain , swelling , loss of function , and hyperthermia are acute postoperative sequelae of inflammation due to tissue injury during surgical procedures . Pharmacologic strategies for minimizing the clinical manifestations of surgical trauma are often directed toward blocking the formation or inhibiting the effects of the biochemical mediators of acute inflammation . This study compared two nonsteroidal anti-inflammatory drugs ( NSAIDs ) , flurbiprofen and ibuprofen , with a prototype glucocorticoid , methylprednisolone , in two replicate placebo-controlled studies for suppression of inflammation due to the surgical removal of impacted third molars . The results indicate that NSAIDs produce greater initial analgesia than do steroids , whereas steroids result in greater suppression of swelling and less loss of function . Examination of the pooled data from the two studies indicates that NSAID pretreatment results in a modest suppression of swelling in comparison with placebo . These data suggest that the acute analgesic effects of NSAIDs in the oral surgery model are due to suppression of a nociceptive process , presumably prostagl and in formation , rather than a generalized anti-inflammatory effect The purpose of this double-blind , r and omized , parallel , multiple-dose study was to compare the efficacy and safety of flurbiprofen with acetaminophen with codeine phosphate in the 96-hr postoperative period following foot surgery . Analysis of mean pain intensity and mean pain relief for the patients not requiring rescue medication did not reveal any significant differences between treatment groups . There were also no significant differences between treatment groups with respect to patient and investigator global evaluations of therapy . The incidence of termination of the study because of side effects was higher for the acetaminophen with codeine group This single-dose , double-blind , r and omized , placebo-controlled study assessed the efficacy and safety of 50 mg of flurbiprofen ( Ansaid , Upjohn ) in the relief of postoperative pain following cesarean section , as well as vaginal or abdominal hysterectomies . Results show that both 50 mg of oral flurbiprofen and 10 mg of intramuscular morphine sulfate were significantly superior to placebo in 161 patients with respect to pain intensity after medication , pain relief scores , need for additional analgesia , and overall clinical evaluation of pain relief . By two hours after treatment , there were no significant differences between morphine sulfate and flurbiprofen in terms of pain intensity or degree of pain relief . According to investigators ' global evaluations of efficacy , both active treatments were statistically superior to placebo . The only adverse reaction occurred in the morphine treatment group . Flurbiprofen administered orally for the relief of moderate to severe pain following major gynecologic surgery appears to be equal to morphine sulfate and superior to placebo in efficacy and safety . Unlike morphine , flurbiprofen is a nonparenteral , uncontrolled substance , and thus patient acceptance is improved while nursing time is decreased & NA ; Post‐operative pain and inflammation are frequently managed with non‐steroidal anti‐inflammatory drugs ( NSAIDs ) . Despite the prevalence of their use , however , relatively little is known about in vivo tissue concentrations of inflammatory mediators at the site of tissue injury and their modulation by NSAIDs . This study compares the effect of oral administration of the NSAID flurbiprofen , to placebo , on tissue levels of immunoreactive prostagl and in E2 ( iPGE2 ) , leukotriene B4 ( iLTB4 ) , and (S)‐flurbiprofen within the surgical wound using implanted microdialysis probes in the dental impaction pain model . Twenty‐four healthy patients in need of extraction of partial to complete bony m and ibular third molars were recruited for this r and omized , double‐blind , placebo‐controlled study . Following pre‐operative administration of N2O/O2 , midazolam i.v . , and regional block anesthesia with 3 % mepivacaine , each patient underwent surgical removal of their impacted third molars . Immediately following completion of the surgery , two semi‐permeable microdialysis probes ( 3 kDa molecular weight cut‐off ) were implanted into each m and ibular surgical site . Patients were taken to a recovery room and microdialysis sample s and patient pain reports ( visual analog scale , VAS ) were collected at 30 min intervals for 4 h. Patients r and omly received either flurbiprofen ( 200 mg orally ) or placebo at the onset of post‐operative pain . Dialysate sample s were collected , frozen , and later assayed for iPGE2 , iLTB4 , and (S)‐flurbiprofen levels . Results of this study show that flurbiprofen decreased post‐operative pain by approximately 70 % compared to placebo‐treated patients ( P<0.001 ) . During the 4 h post‐operative timecourse of this study , flurbiprofen treatment significantly reduced peak tissue levels of iPGE2 ( 9.2±2.6 vs. 0.4±0.15 nM ; P<0.001 ) , without having a significant effect on peak tissue levels of iLTB4 ( 2.5±1.4 vs. 1.49±0.86 nM ) compared to placebo treatment . Levels of (S)‐flurbiprofen significantly increased within the surgical wound exceeding therapeutic levels by 60 min after administration . Flurbiprofen is able to significantly suppress the local production of iPGE2 and provide significant analgesic efficacy without altering iLTB4 tissue levels in this model of acute post‐operative inflammatory pain . These data indicate that NSAIDs selectively alter eicosanoid levels within surgical wound and evoke analgesia at time points coincident with elevated wound levels of the drug . The combined use of microdialysis probes in awake patients who provide simultaneous pain reports may offer insight into peripheral mechanisms of inflammatory mediator release and pain PURPOSE The analgesic efficacy of 50 and 100 mg flurbiprofen was compared with acetaminophen 650 mg , acetaminophen 650 mg plus codeine 60 mg , and placebo . PATIENTS AND METHODS Subjects undergoing the surgical removal of impacted third molars were r and omly administered one of the five treatments after the onset of moderate to severe postoperative pain . Pain intensity , pain relief , and side effects were evaluated for 6 hours after drug administration . RESULTS Both doses of flurbiprofen result ed in significant analgesia in comparison with placebo , acetaminophen , and acetaminophen plus codeine as measured by pain intensity difference , pain relief , and global evaluation . The greatest incidence of side effects occurred in the group receiving acetaminophen plus codeine , and the fewest side effects were reported by subjects administered flurbiprofen . CONCLUSION The results of this study indicate that flurbiprofen is more effective and causes fewer effects than acetaminophen and codeine when used for post-operative dental pain , in ambulatory patients This single-dose , double-blind , r and omized , placebo-controlled study evaluated the analgesic efficacy of both 25 and 50 mg of flurbiprofen ( Ansaid , Upjohn ) compared with 650 mg of aspirin and placebo in 164 patients who had undergone dental impaction surgery . Using the highly sensitive dental pain model , flurbiprofen appears to be an effective , peripherally acting analgesic with a rapid onset of activity . In the current study , it was superior to aspirin in terms of peak effect and duration of action . Although flurbiprofen is much more potent than ibuprofen , its side-effect profile did not differ markedly from that of ibuprofen in this single-dose study & 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 The analgesic effect of flurbiprofen , aspirin and placebo in the treatment of primary dysmenorrhoea was compared in 41 patients using a double blind triple crossover study . No statistically significant differences were found between any pair of treatments and the control for pain relief . Thirty patients had assessment s for all three treatment months , 11 preferred flurbiprofen , 9 preferred placebo , 6 preferred aspirin and 4 had no preference between any of the treatments . Side effects were reported by 14 of the 41 patients : 3 during the control month , 6 during the flurbiprofen month , 4 during the aspirin month and 7 during the placebo month In a single-dose , parallel group , r and omized block treatment allocation study , the relative analgesic efficacy of flurbiprofen , a nonsteroidal antiinflammatory drug , was compared to acetaminophen 650 mg with codeine 60 mg , zomepirac sodium 100 mg , and placebo . A total of 226 post-surgical dental patients ( 146 females and 80 males ) participated in the study . Flurbiprofen in 50 mg and 100 mg dosages demonstrated effective analgesic activity with the 100 mg dosage being at least as effective as the acetaminophen/codeine combination . The results of this study support previous work on flurbiprofen Twenty-five patients suffering from primary dysmenorrhoea took part in a double-blind crossover study which demonstrated flurbiprofen ( 100 mg three times a day ) to be significantly more effective than paracetamol ( 1 g three times a day ) in providing pain relief on Days 1 and 2 , and on the worst day of pain . Flurbiprofen also appeared to reduce the incidence of secondary symptoms of nausea and feeling faint , and menstrual blood loss . The study was also analyzed as if a parallel group study and showed flurbiprofen to be significantly more effective than paracetamol One hundred sixty-four out patients with postoperative pain after the removal of impacted third molars were r and omly assigned on a double-blind basis , to receive oral doses of flurbiprofen 25 , 50 , or 100 mg ; aspirin 600 mg ; or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 8 hours after medicating . Estimates of sum of pain differences ( SPID ) , peak pain intensity difference ( PID ) , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . All active medications were significantly superior to placebo . Analgesia was similar for flurbiprofen 25 mg and aspirin 600 mg . Flurbiprofen 50 and 100 mg were significantly superior to aspirin for every measure of analgesia except peak PID . There was a significant dose-response regression between flurbiprofen 25 mg and both of the higher dosages . Flurbiprofen 50 and 100 mg did not differ significantly , suggesting a plateau in flurbiprofen 's analgesia . The analgesic effect of flurbiprofen was significant by hour 1 and persisted for 8 hours . The frequency of adverse effects was similar for the active medications Our purpose was to evaluate the analgesic efficacy and safety of single oral doses of flurbiprofen 25 , 50 and 100 mg , aspirin 600 mg , and placebo in the relief of moderate to severe post-episiotomy pain . One hundred and fifty-two evaluable patients completed a r and omized , double-blind , stratified , parallel groups study . They were observed over a six hour period by one nurse-observer . Based upon each of the summary efficacy measures SPID , TOTAL and PEAK % and most of the hourly direct measures of pain intensity and pain relief , each of the four active treatments were statistically superior to placebo . Flurbiprofen 25 mg appeared to be slightly less effective than aspirin 600 mg , but the differences were not statistically significant . Flurbiprofen 50 and 100 mg were quite similar and were significantly more effective than aspirin 600 mg and flurbiprofen 25 mg . There were no observed or reported adverse effects In a four week double-blind crossover study , flurbiprofen 200 mg daily was compared with naproxen 750 mg daily in the management of 30 patients with ankylosing spondylitis . Both treatments were found to be very effective in alleviating pain and stiffness . No significant difference in efficacy was discernible between the two drugs . Side-effects were more frequent with flurbiprofen . A small , but significant , increase in renal excretion of beta-n-acetyl glucosaminidase occurred during treatment with both naproxen and flurbiprofen . Although previous surveys have not shown evidence of renal damage , further surveillance of renal function in patients receiving long term treatment with these preparations to exclude possible renal impairment would be prudent 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 In this r and omized , double-blind study , 57 patients with ankylosing spondylitis were evaluated after 26 weeks of treatment with either flurbiprofen ( Ansaid , Upjohn ) or indomethacin . Flurbiprofen administered four times a day in a total daily dose of 200 mg was effective in controlling the pain and associated symptoms of ankylosing spondylitis . Pain was adequately controlled in some patients following a total daily dose of 100 mg of flurbiprofen administered twice a day . Flurbiprofen was as effective as indomethacin in most key efficacy measurements analyzed . The drug was well tolerated in doses of up to 300 mg per day , and no clinical ly significant laboratory abnormalities were detected . Flurbiprofen is an excellent treatment for the control of pain and inflammation in patients with ankylosing spondylitis Nonsteroidal anti-inflammatory drugs produce their analgesic and adverse effects through interaction with cyclooxygenase in a variety of tissues . The authors evaluated the therapeutic potential of administering a sustained-release formulation of flurbiprofen into a surgical wound following oral surgery to produce analgesia at the site of injury while minimizing exposure to potential targets for toxicity . Subjects ( N = 98 ) received 1 of 8 treatments : flurbiprofen in a microparticle formulation in doses of 3.125 mg , 6.25 mg , 12.5 mg , 25 mg , or 50 mg ; PO flurbiprofen 25 mg or 50 mg ; or placebo . The flurbiprofen microparticle formulation or matching placebo was placed into the extraction sites at the end of surgery ( removal of 2 lower impacted third molars ) . The sum of the pain visual analog scale over the 6-hour observation period demonstrated significantly less pain ( P < .05 ) for flurbiprofen microparticle in comparison with placebo . Fewer subjects remedicated in the flurbiprofen microparticle drug groups , primarily for the 12.5-mg and higher doses . The incidence of adverse effects and local complications did not differ across groups . These data suggest that direct administration of flurbiprofen in a microparticle formulation at a site of tissue injury delays the onset and lowers the intensity of postoperative pain at lower doses than usually administered orally The analgesic efficacy of a single 50-mg preoperative dose of flurbiprofen was compared with ACC-30 ( aspirin 375 mg , codeine 30 mg , caffeine 30 mg ) and a placebo . Forty patients scheduled for the surgical removal of impacted maxillary third molars were enrolled in a double-blind , r and omized study . Using a within-subject design we compared the analgesic efficacy of ( 1 ) preoperative flurbiprofen 50 mg with placebo in 20 patients , and ( 2 ) preoperative ACC-30 with placebo in 20 other patients . Using a between-group design , we then compared the analgesic efficacy of ( 3 ) each drug given preoperatively and postoperatively , and ( 4 ) each drug given postoperatively only . Patients rated 2 pain dimensions , intensity and unpleasantness , hourly for 8 hours after the presurgical dose . The results of this study indicate that better analgesia was obtained when flurbiprofen was given preoperatively compared to only after surgery . Conversely , preoperative administration of ACC-30 did not demonstrate any significant influence on postsurgical analgesia . When comparing the 2 drugs , flurbiprofen proved to be superior in providing pain relief only when it was given prior to surgery . There was no difference between them when given only after surgery . Side effects were moderate and not significantly different between patients receiving flurbiprofen and those receiving ACC-30 The ideal anti-inflammatory agent for use in third molar surgery should control pain , reduce swelling and trismus , and have no unwanted side effects . This investigation evaluated and compared the efficacy of corticosteroids , nonsteroidal anti-inflammatory agents , and placebo for reduction of the acute postoperative inflammatory response and its undesirable sequelae in patients undergoing the surgical removal of impacted third molars . Corticosteroids appeared to have maximal effect in controlling edema but had minimal analgesic effects . Nonsteroidal anti-inflammatory agents appear to be effective analgesics . A combination of these agents may be necessary to control the sequelae of oral surgical procedures most effectively Eighty-eight out patients with postoperative pain after the surgical removal of impacted third molars were r and omly assigned , on a double-blind basis , to receive a single , oral dose of flurbiprofen 100 mg , acetaminophen 600 mg , a combination of acetaminophen 600 mg with codeine 60 mg , or placebo . Using a self-rating record , subjects rated their pain and its relief hourly for 12 hours after medicating . Estimates of sum of pain intensity differences , peak pain intensity differences , total relief , peak relief , and hours of 50 % relief were derived from these subjective reports . Flurbiprofen and the acetaminophen-codeine combination were significantly superior to placebo for every measure of total and peak analgesia and significantly superior to acetaminophen alone for most measures of efficacy . Based on the 12-hour data , acetaminophen alone did not differ significantly from placebo ; however , it was superior to placebo for measures of total effect based on the 4-hour data . Flurbiprofen was significantly superior to the acetaminophen codeine combination with respect to the number of hours until remedication . All medications had manifested an effect by hour 1 ; analgesia persisted for 12 hours for flurbiprofen , 6 hours for acetaminophen-codeine , and 3 hours for acetaminophen alone . The frequency of adverse effects was similar for the active medications The relative analgesic efficacy and safety of single oral doses of 50 and 100 mg of flurbiprofen ( Ansaid , Upjohn ) were compared with 100 mg of zomepirac sodium , 650 mg of acetaminophen plus 60 mg of codeine , 650 mg of acetaminophen alone , and placebo in a r and omized , double-blind , parallel-group study . A total of 182 patients entered the study with moderate pain from a third molar extraction and were evaluated for six hours . For many efficacy variables , all active treatments were significantly ( p less than or equal to 0.05 ) more effective than placebo . The two doses of flurbiprofen gave approximately similar results , suggesting a plateau effect above 50 mg . With the exception of relief at one hour , there were no significant differences between zomepirac and either dose of flurbiprofen . However , the mean response with zomepirac was greater than with either 50 or 100 mg of flurbiprofen during the first four hours and lower during the last two hours . The analgesic effects of acetaminophen alone were not significantly different from acetaminophen in combination with codeine . At the first hour , acetaminophen plus codeine led to significantly better pain relief than did 100 mg of flurbiprofen . After the first hour , flurbiprofen result ed in greater mean scores than acetaminophen alone or acetaminophen plus codeine , and these differences were significant at the fifth and sixth hours . Five patients had adverse reactions while receiving acetaminophen , acetaminophen plus codeine , or placebo . There were no adverse effects with flurbiprofen or zomepirac |
12,109 | 23,949,842 | The initial treatment of people with advanced NSCLC is palliative , and carboplatin can be a treatment option .
It has a similar effect on survival but a different toxicity profile when compared with cisplatin . | BACKGROUND An estimated 220,000 new cases of non-small cell lung cancer ( NSCLC ) and 160,000 deaths are expected to occur in the US in 2013 , representing about 28 % of cancer-related mortality .
Approximately 75 % of these people will have locally advanced or metastatic disease and will be treated in a palliative setting .
Platinum-based combination chemotherapy has benefits in terms of survival and symptom control when compared with best supportive care .
OBJECTIVES To assess the efficacy and safety of carboplatin-based chemotherapy when compared with cisplatin-based chemotherapy , both in combination with a third-generation drug , in people with advanced NSCLC .
To compare quality of life in people with advanced NSCLC receiving chemotherapy with cisplatin and carboplatin combined with a third-generation drug . | The frequent need to obtain an estimate of renal function in cancer patients , not least for targeting carboplatin dose , has led to a number of approaches to estimate glomerular filtration rate ( GFR ) . This study aim ed to develop a simple and reliable method to estimate GFR using readily-available patient characteristics . Data from 62 patients with estimates of 51Cr-EDTA clearance were analysed to determine the most appropriate formula relating this method of measuring GFR to patient characteristics . The population pharmacokinetics of 51Cr-EDTA were analysed using NONMEM to evaluate the influence of each covariate . The formulae derived were then vali date d using a further 38 patients and compared with those obtained using existing formulae 51Cr-EDTA clearance ( GFR ) was positively related to Dubois surface area , negatively related to age , and inversely related to serum creatinine ( SCr ) . Females had lower 51Cr-EDTA clearance than males . The enzymatic method of SCr assay gave more reliable results than the Jaffe colorimetric method . A measure of creatine kinase significantly improved the estimation of GFR . The new formula produced estimates of GFR which were less biased ( Mean Prediction Error = –3 % ) and more precise ( Mean Absolute Prediction Error = 12 % ) than Cockcroft and Gault ( –8 % and 16 % ) or Jelliffe ( –15 % and 19 % ) estimates . The formulae developed here can be used to provide reliable estimates of GFR , particularly in regard to targeted dosing of carboplatin . © 2001 Cancer Research BACKGROUND Assessment of the change in tumour burden is an important feature of the clinical evaluation of cancer therapeutics : both tumour shrinkage ( objective response ) and disease progression are useful endpoints in clinical trials . Since RECIST was published in 2000 , many investigators , cooperative groups , industry and government authorities have adopted these criteria in the assessment of treatment outcomes . However , a number of questions and issues have arisen which have led to the development of a revised RECIST guideline ( version 1.1 ) . Evidence for changes , summarised in separate papers in this special issue , has come from assessment of a large data warehouse ( > 6500 patients ) , simulation studies and literature review s. HIGHLIGHTS OF REVISED RECIST 1.1 : Major changes include : Number of lesions to be assessed : based on evidence from numerous trial data bases merged into a data warehouse for analysis purpose s , the number of lesions required to assess tumour burden for response determination has been reduced from a maximum of 10 to a maximum of five total ( and from five to two per organ , maximum ) . Assessment of pathological lymph nodes is now incorporated : nodes with a short axis of 15 mm are considered measurable and assessable as target lesions . The short axis measurement should be included in the sum of lesions in calculation of tumour response . Nodes that shrink to < 10 mm short axis are considered normal . Confirmation of response is required for trials with response primary endpoint but is no longer required in r and omised studies since the control arm serves as appropriate means of interpretation of data . Disease progression is clarified in several aspects : in addition to the previous definition of progression in target disease of 20 % increase in sum , a 5 mm absolute increase is now required as well to guard against over calling PD when the total sum is very small . Furthermore , there is guidance offered on what constitutes ' unequivocal progression ' of non-measurable/non-target disease , a source of confusion in the original RECIST guideline . Finally , a section on detection of new lesions , including the interpretation of FDG-PET scan assessment is included . Imaging guidance : the revised RECIST includes a new imaging appendix with up date d recommendations on the optimal anatomical assessment of lesions . FUTURE WORK A key question considered by the RECIST Working Group in developing RECIST 1.1 was whether it was appropriate to move from anatomic unidimensional assessment of tumour burden to either volumetric anatomical assessment or to functional assessment with PET or MRI . It was concluded that , at present , there is not sufficient st and ardisation or evidence to ab and on anatomical assessment of tumour burden . The only exception to this is in the use of FDG-PET imaging as an adjunct to determination of progression . As is detailed in the final paper in this special issue , the use of these promising newer approaches requires appropriate clinical validation studies BACKGROUND To compare the efficacy and toxicity of paclitaxel-carboplatin ( TAX-CBP ) and paclitaxel-cisplatin ( TAX-DDP ) chemotherapy protocol s for advanced non-small cell lung cancer . METHODS One hundred and twenty-six patients with non-small cell lung cancer were r and omized into TAX-DDP and TAX-CBP groups . TAX-CBP group : TAX 175 mg/m² and CBP 350 mg/m² , d1 iv ; TAX-DDP group : TAX 175 mg/m² and DDP 100 mg/m² d1 iv . The therapy was repeated every 28 days . The response rate was assessed after three treatments . RESULTS TAX-CBP group : response rate ( RR ) was 36 % ( 22/61 ) , 1-year survival rate was 34.1 % . TAX-DDP group : RR was 33.9 % (21/62),1-year survival rate was 33.1 % . There was no significant difference of RR and 1-year survival rate between TAX-CBP and TAX-DDP group ( P>0.05 ) . The median survival time of TAX-CBP group ( 11.2 months ) was significant higher than that of TAX-DDP group ( 9 months ) ( P<0.05 ) . The major toxicity associated with paclitaxel included alpecia , myelosuppression , gastrointestinal reaction and myalgia or arthralgia . The thrombocytopenia in TAX-CBP group was more severe than that in TAX-DDP group ( P<0.05 ) . The Gastrointestinal and myalgia or arthralgia in TAX-DDP group were more severe than those in TAX-CBP group ( P<0.05 ) . CONCLUSIONS TAX-CBP and TAX-DDP chemotherapy may be used as first choice protocol in the chemotherapy of non-small cell lung cancer In controlled clinical trials there are usually several prognostic factors known or thought to influence the patient 's ability to respond to treatment . Therefore , the method of sequential treatment assignment needs to be design ed so that treatment balance is simultaneously achieved across all such patients factor . Traditional methods of restricted r and omization such as " permuted blocks within strata " prove inadequate once the number of strata , or combinations of factor levels , approaches the sample size . A new general procedure for treatment assignment is described which concentrates on minimizing imbalance in the distributions of treatment numbers within the levels of each individual prognostic factor . The improved treatment balance obtained by this approach is explored using simulation for a simple model of a clinical trial . Further discussion centers on the selection , predictability and practicability of such a procedure Background : Bevacizumab , the anti-vascular endothelial growth factor agent , provides clinical benefit when combined with platinum-based chemotherapy in first-line advanced non-small-cell lung cancer . We report the final overall survival ( OS ) analysis from the phase III AVAiL trial . Patients and methods : Patients ( n = 1043 ) received cisplatin 80 mg/m2 and gemcitabine 1250 mg/m2 for up to six cycles plus bevacizumab 7.5 mg/kg ( n = 345 ) , bevacizumab 15 mg/kg ( n = 351 ) or placebo ( n = 347 ) every 3 weeks until progression . Primary end point was progression-free survival ( PFS ) ; OS was a secondary end point . Results : Significant PFS prolongation with bevacizumab compared with placebo was maintained with longer follow-up { hazard ratio ( HR ) [ 95 % confidence interval ( CI ) ] 0.75 ( 0.64–0.87 ) , P = 0.0003 and 0.85 ( 0.73–1.00 ) , P = 0.0456 } for the 7.5 and 15 mg/kg groups , respectively . Median OS was > 13 months in all treatment groups ; nevertheless , OS was not significantly increased with bevacizumab [ HR ( 95 % CI ) 0.93 ( 0.78–1.11 ) , P = 0.420 and 1.03 ( 0.86–1.23 ) , P = 0.761 ] for the 7.5 and 15 mg/kg groups , respectively , versus placebo . Most patients ( ∼62 % ) received multiple lines of post study treatment . Up date d safety results are consistent with those previously reported . Conclusions : Final analysis of AVAiL confirms the efficacy of bevacizumab when combined with cisplatin – gemcitabine . The PFS benefit did not translate into a significant OS benefit , possibly due to high use of efficacious second-line therapies BACKGROUND Bevacizumab , a monoclonal antibody against vascular endothelial growth factor , has been shown to benefit patients with a variety of cancers . METHODS Between July 2001 and April 2004 , the Eastern Cooperative Oncology Group ( ECOG ) conducted a r and omized study in which 878 patients with recurrent or advanced non-small-cell lung cancer ( stage IIIB or IV ) were assigned to chemotherapy with paclitaxel and carboplatin alone ( 444 ) or paclitaxel and carboplatin plus bevacizumab ( 434 ) . Chemotherapy was administered every 3 weeks for six cycles , and bevacizumab was administered every 3 weeks until disease progression was evident or toxic effects were intolerable . Patients with squamous-cell tumors , brain metastases , clinical ly significant hemoptysis , or inadequate organ function or performance status ( ECOG performance status , > 1 ) were excluded . The primary end point was overall survival . RESULTS The median survival was 12.3 months in the group assigned to chemotherapy plus bevacizumab , as compared with 10.3 months in the chemotherapy-alone group ( hazard ratio for death , 0.79 ; P=0.003 ) . The median progression-free survival in the two groups was 6.2 and 4.5 months , respectively ( hazard ratio for disease progression , 0.66 ; P<0.001 ) , with corresponding response rates of 35 % and 15 % ( P<0.001 ) . Rates of clinical ly significant bleeding were 4.4 % and 0.7 % , respectively ( P<0.001 ) . There were 15 treatment-related deaths in the chemotherapy-plus-bevacizumab group , including 5 from pulmonary hemorrhage . CONCLUSIONS The addition of bevacizumab to paclitaxel plus carboplatin in the treatment of selected patients with non-small-cell lung cancer has a significant survival benefit with the risk of increased treatment-related deaths . ( Clinical Trials.gov number , NCT00021060 . BACKGROUND In advanced not selected NSCLC chemotherapy achieved an advantage of approximately 1 - 2 months on median survival versus best supportive care . Chemotherapy seems to improve symptoms control , even if r and omised studies with quality of life as first endpoint are lacking and often chemotherapy toxicity compromises the frail cost/benefit ratio . The aim of the present study is to evaluate the impact on QoL , substituting cisplatin , a pivot drug in NSCLC therapy , with carboplatin , an analogue with an improved toxicity profile . The combination of cisplatin with Mitomycin and Vinblastine was one of the most frequently used in the palliative setting at the time of design of our study . METHODS Patients were r and omized to receive MVP regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Cisplatin 100 mg/m2 d1 ) or MVC regimen ( Mitomycin-C 8 mg/m2 d1 , Vinblastine 4 mg/m2 d 1 - 8 , Carboplatin 300 mg/m2 d1 ) every 3 weeks . The QoL was evaluated by the Spitzer QL-Index and by the EORTC QLQ-C30+LC 13 question naires before chemotherapy , after one cycle , after three cycles , and then every 6 weeks in the first 6 months and every 3 months thenafter . RESULTS From September 1994 to July 1997 , 153 consecutive patients were r and omized to MVP ( 75 patients ) or MVC arm ( 78 patients ) . Despite difficulties in carrying out and analysing QoL items in such patients , the global QoL evaluated by the Spitzer 's question naire suggested an advantage for MVC regimen ( P=0.05 ) and a significant difference was observed in global health subdomain ( P=0.04 ) . The disease-related symptoms improved with time , and the benefits lasted for the entire treatment period . When evaluated with the EORTC question naire there was significantly less nausea and vomiting ( P=0.0001 ) , appetite loss ( P=0.01 ) , insomnia ( P=0.03 ) , constipation ( P=0.01 ) and peripheral neuropathy ( P=0.01 ) in favour of MVC , and a trend for less hair loss ( P=0.05 ) . The advantage lasted for all the duration of chemotherapy . No differences were observed in global quality of life subdomain ( P=0.40 ) between the two regimen . QoL was the first endpoint and the statistical power was inadequate to assess other parameters . However , we reported a response rate of 43.1 and 38.6 % , respectively , in MVP and MVC arm ( P=0.59 ) and a median survival of 10.2 and 7.2 months , respectively , for cisplatin and carboplatin arm ( P=0.39 ) . CONCLUSIONS The carboplatin containing regimen ( MVC ) has a significant better toxicity profile than the cisplatin containing ( MVP ) regimen as proven both by the EORTC question naires and by the WHO toxicity data reported by physicians . No significant differences in terms of response rate , time to progression and overall survival were observed between the two regimen . The two chemotherapy regimen showed a similar effectiveness in symptom palliation when evaluated with C30 addendum of EORTC QOL question naire . With the Spitzer 's question naires a trend towards an improved quality of life index was observed during treatment with the carboplatin combination in comparison to the cisplatin combination . This difference , however , was not observed when the global quality of life was evaluated with the EORTC patients compiled question naires . A carboplatin containing regimen with better toxicity profile and a similar potentiality for symptoms control offers an option in comparison to similar cisplatin containing combinations in the palliative treatment of advanced NSCLC The purpose of this article is to provide up date d recommendations for the treatment of patients with stage IV non-small-cell lung cancer . A literature search identified relevant r and omized trials published since 2002 . The scope of the guideline was narrowed to chemotherapy and biologic therapy . An Up date Committee review ed the literature and made up date d recommendations . One hundred sixty-two publications met the inclusion criteria . Recommendations were based on treatment strategies that improve overall survival . Treatments that improve only progression-free survival prompted scrutiny of toxicity and quality of life . For first-line therapy in patients with performance status of 0 or 1 , a platinum-based two-drug combination of cytotoxic drugs is recommended . Nonplatinum cytotoxic doublets are acceptable for patients with contraindications to platinum therapy . For patients with performance status of 2 , a single cytotoxic drug is sufficient . Stop first-line cytotoxic chemotherapy at disease progression or after four cycles in patients who are not responding to treatment . Stop two-drug cytotoxic chemotherapy at six cycles even in patients who are responding to therapy . The first-line use of gefitinib may be recommended for patients with known epidermal growth factor receptor ( EGFR ) mutation ; for negative or unknown EGFR mutation status , cytotoxic chemotherapy is preferred . Bevacizumab is recommended with carboplatin-paclitaxel , except for patients with certain clinical characteristics . Cetuximab is recommended with cisplatin-vinorelbine for patients with EGFR-positive tumors by immunohistochemistry . Docetaxel , erlotinib , gefitinib , or pemetrexed is recommended as second-line therapy . Erlotinib is recommended as third-line therapy for patients who have not received prior erlotinib or gefitinib . Data are insufficient to recommend the routine third-line use of cytotoxic drugs . Data are insufficient to recommend routine use of molecular markers to select chemotherapy BACKGROUND To observe the efficacy and toxicity of gemcitabine plus carboplatin ( GCarb ) versus gemcitabine plus cisplatin ( GCis ) in the treatment of advanced non-small cell lung cancer ( NSCLC ) . METHODS Forty patients with histologically confirmed NSCLC were r and omized to enter the study . GCarb group : Gemcitabine 1 000 mg/m² IV on day 1,8 ; carboplatin AUC 4 - 6 IV on day 1 . GCis group : Gemcitabine 1 000 mg/m² IV on day 1,8 ; cisplatin 30 - 40 mg/m² IV on day 1 - 3 . RESULTS The response rate was 65 % and 60 % for GCarb group and GCis group respectively ( P > 0.5 ) . Toxicities included myelosuppression , digestive reaction , alopecia and rash . Digestive toxicity in GCarb group was less than that in GCis group ( P < 0.05 ) . CONCLUSIONS Both GCarb and GCis regimes can be used as first-line protocol in the chemotherapy of non small cell lung cancer Paclitaxel plus carboplatin ( CAR ) or cisplatin ( CIS ) has shown activity in the treatment of advanced non-small cell lung cancer ( NSCLC ) . Our aim was to determine whether paclitaxel plus platinum is an appropriate regimen for chemo-naïve NSCLC in patients aged 70 years or older . Patients were r and omized into paclitaxel plus CAR or paclitaxel plus CIS treatment arms . Treatment consisted of paclitaxel 160 mg/m2 and carboplatin at AUC = 6 ( predicted using measured clearances and the Calvert formula ) IV infusion on day 1 every 3 weeks , or paclitaxel 160 mg/m2 and cisplatin 60 mg/m2 IV on day 1 every 3 weeks . In total , 81 patients were enrolled from September 2000 to February 2005 , including 40 who received CAR treatment and 41 who received CIS treatment . In all , 152 cycles of CAR ( median , four cycles per patient ) and 172 cycles of CIS ( median , four cycles per patient ) were given . Each arm had one complete response and 15 partial responses to the treatment , with overall response rates of 40 % and 39 % , respectively . Myelosuppression was mild in both arms , and there was no statistical difference between the two arms . Alopecia ( P < 0.001 ) , peripheral neuropathy ( P = 0.017 ) , and fatigue ( P < 0.001 ) were more severe in the CIS treatment arm than in the CAR treatment arm . Median time to disease progression was 6.6 months in the CAR arm and 6.9 months in the CIS arm . Median survival time was 10.3 months in the CAR arm and 10.5 months in the CIS arm . In conclusion , paclitaxel plus CAR or CIS treatment is feasible in elderly patients and has similar activity . However , paclitaxel plus CAR had less non-hematological toxicity than paclitaxel plus CIS PURPOSE This r and omized , multicenter , phase III trial was conducted to compare the tolerability of gemcitabine plus cisplatin ( GP ) vs. gemcitabine plus carboplatin ( GC ) in chemonaive patients with stage IIIb and IV non-small cell lung carcinoma ( NSCLC ) . Secondary objectives were to evaluate response , duration of response , time to progressive disease ( TTPD ) , and survival . PATIENTS AND METHODS Eligible patients were required to have stage IIIb or IV NSCLC , no previous chemotherapy , Karnofsky performance status of at least 70 , bidimensionally measurable disease , and age 18 - 75 years . R and omized patients in both arms were given gemcitabine 1200 mg/m(2 ) on days 1 and 8 , followed on day 1 by cisplatin 80 mg/m(2 ) ( GP ) or carboplatin AUC=5 ( GC ) . Treatment cycles were repeated every 21 days for a maximum of six cycles , or until disease progression or unacceptable toxicity occurred . RESULTS Enrolled patients in both arms , 87 in GP and 89 in GC , were well balanced for demographics and disease characteristics . Dose intensity was 93.8 and 92.7 % for gemcitabine in GP/GC arms , respectively ; 97.7 % for cisplatin and 99.9 % for carboplatin . Patients with at least one grade 3/4 toxicity excluding nausea , vomiting or alopecia , were 44 % in GP arm and 54 % in GC arm . The only significantly different toxicities were , nausea and vomiting in GP and thrombocytopenia in GC group . The overall response rates , median TTPD , response duration and survival were , 41/29 % , 5.87/4.75 months , 7.48/5.15 months , and 8.75/7.97 months for GP and GC arms , respectively . CONCLUSION GP and GC are effective and feasible regimens for advanced NSCLC , and are comparable in efficacy and toxicity . GC may offer acceptable option to patients with advanced NSCLC , especially those who are unable to receive cisplatin PURPOSE To investigate whether docetaxel plus platinum regimens improve survival and affect quality of life ( QoL ) in advanced non-small-cell lung cancer ( NSCLC ) compared with vinorelbine plus cisplatin as first-line chemotherapy . PATIENTS AND METHODS Patients ( n = 1,218 ) with stage IIIB to IV NSCLC were r and omly assigned to receive docetaxel 75 mg/m2 and cisplatin 75 mg/m2 every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin area under the curve of 6 mg/mL * min every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/wk and cisplatin 100 mg/m2 every 4 weeks ( VC ) . RESULTS Patients treated with DC had a median survival of 11.3 v 10.1 months for VC-treated patients ( P = .044 ; hazard ratio , 1.183 [ 97.2 % confidence interval , 0.989 to 1.416 ] ) . The 2-year survival rate was 21 % for DC-treated patients and 14 % for VC-treated patients . Overall response rate was 31.6 % for DC-treated patients v 24.5 % for VC-treated patients ( P = .029 ) . Median survival ( 9.4 v 9.9 months [ for VC ] ; P = .657 ; hazard ratio , 1.048 [ 97.2 confidence interval , 0.877 to 1.253 ] ) and response ( 23.9 % ) with DCb were similar to those results for VC . Neutropenia , thrombocytopenia , infection , and febrile neutropenia were similar with all three regimens . Grade 3 to 4 anemia , nausea , and vomiting were more common ( P < .01 ) with VC than with DC or DCb . Patients treated with either docetaxel regimen had consistently improved QoL compared with VC-treated patients , who experienced deterioration in QoL. CONCLUSION DC result ed in a more favorable overall response and survival rate than VC . Both DC and DCb were better tolerated and provided patients with consistently improved QoL compared with VC . These findings demonstrate that a docetaxel plus platinum combination is an effective treatment option with a favorable therapeutic index for first-line treatment of advanced or metastatic NSCLC BACKGROUND Patients with advanced non-small cell lung cancer ( NSCLC ) do not have curative treatment options ; therefore , treatments should prolong survival and improve quality of life ( QoL ) . We compared the effect on QoL of two docetaxel-platinum regimens with vinorelbine-cisplatin . METHODS QoL was assessed by the Lung Cancer Symptom Scale ( LCSS ) and the general EuroQol five-dimensional question naire ( EQ-5D ) in 926 chemotherapy-naïve patients with stages IIIB to IV NSCLC . Patients were r and omly assigned to receive : docetaxel 75 mg/m2 plus cisplatin 75 mg/m2 , every 3 weeks ( DC ) ; docetaxel 75 mg/m2 and carboplatin 6 mg/ml min , every 3 weeks ( DCb ) ; or vinorelbine 25 mg/m2/week plus cisplatin 100 mg/m2 , every 4 weeks ( VC ) . RESULTS Overall , patients treated with either docetaxel-containing regimen had better QoL than VC-treated patients ( LCSS global item " QoL today " : P=0.064 for DC and P=0.016 for DCb versus VC ; EQ-5D global item " health state today " : P=0.016 for DC and P<0.001 for DCb versus VC ) . DC-treated patients experienced improved pain relief compared with VC ( P=0.033 ) , whereas pain relief with DCb and VC was similar . Patients treated with either docetaxel regimen had more favorable changes in performance status ( P=0.065 for DC and P<0.001 for DCb versus VC ) and mean weight loss ( 0.06 kg , gain of 0.08 kg , and 2.27 kg for DC , DCb , and VC , respectively ; P<0.001 for both DC versus VC and DCb versus VC ) . CONCLUSION The TAX 326 study shows that docetaxel-platinum regimens relieve symptoms and improve QoL in patients with advanced NSCLC . DCb and DC were superior to VC in all QoL outcomes assessed except for the difference between DC and VC in LCSS " QoL today " , which was not significant Eastern Cooperative Oncology Group ( ECOG ) Study E1594 compared paclitaxel and cisplatin with three newer chemotherapy doublets in the treatment of patients with advanced nonsmall cell lung carcinoma ( NSCLC ) . The accrual of patients with an ECOG performance status ( PS ) of 2 was discontinued due to a perceived rate of unacceptable toxicity BACKGROUND The combination of paclitaxel with cisplatin or carboplatin has significant activity in non-small-cell lung cancer ( NSCLC ) . This phase III study of chemotherapy-naïve advanced NSCLC patients was design ed to assess whether response rate in patients receiving a paclitaxel/carboplatin combination was similar to that in patients receiving a paclitaxel/cisplatin combination . Paclitaxel was given at a dose of 200 mg/m(2 ) ( 3-h intravenous infusion ) followed by either carboplatin at an AUC of 6 or cisplatin at a dose of 80 mg/m(2 ) , all repeated every 3 weeks . Survival , toxicity and quality of life were also compared . PATIENTS AND METHODS Patients were r and omised to receive one of the two combinations , stratified according to centre , performance status , disease stage and histology . The primary analyses of response rate and survival were carried out on response-evaluable patients . Survival was also analysed for all r and omised patients . Toxicity analyses were carried out on all treated patients . RESULTS A total of 618 patients were r and omised . The two treatment arms were well balanced with regard to gender ( 83 % male ) , age ( median 58 years ) , performance status ( 83 % ECOG 0 - 1 ) , stage ( 68 % IV , 32 % IIIB ) and histology ( 38 % squamous cell carcinoma ) . In the paclitaxel/carboplatin arm , 306 patients received a total of 1311 courses ( median four courses , range 1 - 10 courses ) while in the paclitaxel/cisplatin arm , 302 patients received a total of 1321 courses ( median four courses , range 1 - 10 courses ) . In only 76 % of courses , carboplatin was administered as planned at an AUC of 6 , while in 96 % of courses , cisplatin was given at the planned dose of 80 mg/m(2 ) . The response rate was 25 % ( 70 of 279 ) in the paclitaxel/carboplatin arm and 28 % ( 80 of 284 ) in the paclitaxel/cisplatin arm ( P = 0.45 ) . Responses were review ed by an independent radiological committee . For all r and omised patients , median survival was 8.5 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm [ hazard ratio 1.20 , 90 % confidence interval ( CI ) 1.03 - 1.40 ] ; the 1-year survival rates were 33 % and 38 % , respectively . On the same data set , a survival up date after 22 months of additional follow-up yielded a median survival of 8.2 months in the paclitaxel/carboplatin arm and 9.8 months in the paclitaxel/cisplatin arm ( hazard ratio 1.22 , 90 % CI 1.06 - 1.40 ; P = 0.019 ) ; the 2-year survival rates were 9 % and 15 % , respectively . Excluding neutropenia and thrombocytopenia , which were more frequent in the paclitaxel/carboplatin arm , and nausea/vomiting and nephrotoxicity , which were more frequent in the paclitaxel/cisplatin arm , the rate of severe toxicities was generally low and comparable between the two arms . Overall quality of life ( EORTC QLQ-C30 and LC-13 ) was also similar between the two arms . CONCLUSIONS This is the first trial comparing carboplatin and cisplatin in the treatment of advanced NSCLC . Although paclitaxel/carboplatin yielded a similar response rate , the significantly longer median survival obtained with paclitaxel/cisplatin indicates that cisplatin-based chemotherapy should be the first treatment option BACKGROUND We conducted a phase II r and omized study to assess the efficacy , with response as the primary endpoint , and the toxicity of gemcitabine/cisplatin ( GP ) and gemcitabine/carboplatin ( GC ) in patients with advanced non-small cell lung cancer ( NSCLC ) . METHODS Patients were r and omized to GP ( gemcitabine 1200 mg/m(2 ) , days 1 and 8 plus cisplatin 80 mg/m(2 ) day 2 ) or GC ( gemcitabine 1200 mg/m(2 ) , days 1 and 8 plus carboplatin AUC=5 day 2 ) . Cycles were repeated every 3 weeks . RESULTS Sixty-two patients were r and omized to GP and 58 to GC . A total of 533 cycles were delivered ( 264 GP , 269 GC ) , with a median of four cycles/patient . The objective response rate was 41.9 % ( 95 % C.I. , 29.6 - 54.2 % ) for GP and 31.0 % ( 95 % C.I. , 18.2 - 42.8 % ) for GC ( P=0.29 ) . No significant differences between arms were observed in median survival ( 10.4 months GP , 10.8 months GC ) and median time to progression ( 5.4 months GP , 5.1 months GC ) . Both regimens were very well tolerated with no statistical differences between arms in grade 3/4 toxicities . When all toxicity grade s were combined , emesis , neuropathy and renal toxicity occurred more frequently on the GP arm ( P<0.005 ) . CONCLUSIONS GC arm did not provide a significant difference in response rate compared with GP arm , with better overall tolerability . Carboplatin could be a valid alternative to cisplatin in the palliative setting PURPOSE Cisplatin plus gemcitabine is a st and ard regimen for first-line treatment of advanced non-small-cell lung cancer ( NSCLC ) . Phase II studies of pemetrexed plus platinum compounds have also shown activity in this setting . PATIENTS AND METHODS This noninferiority , phase III , r and omized study compared the overall survival between treatment arms using a fixed margin method ( hazard ratio [ HR ] < 1.176 ) in 1,725 chemotherapy-naive patients with stage IIIB or IV NSCLC and an Eastern Cooperative Oncology Group performance status of 0 to 1 . Patients received cisplatin 75 mg/m(2 ) on day 1 and gemcitabine 1,250 mg/m(2 ) on days 1 and 8 ( n = 863 ) or cisplatin 75 mg/m(2 ) and pemetrexed 500 mg/m(2 ) on day 1 ( n = 862 ) every 3 weeks for up to six cycles . RESULTS Overall survival for cisplatin/pemetrexed was noninferior to cisplatin/gemcitabine ( median survival , 10.3 v 10.3 months , respectively ; HR = 0.94 ; 95 % CI , 0.84 to 1.05 ) . Overall survival was statistically superior for cisplatin/pemetrexed versus cisplatin/gemcitabine in patients with adenocarcinoma ( n = 847 ; 12.6 v 10.9 months , respectively ) and large-cell carcinoma histology ( n = 153 ; 10.4 v 6.7 months , respectively ) . In contrast , in patients with squamous cell histology , there was a significant improvement in survival with cisplatin/gemcitabine versus cisplatin/pemetrexed ( n = 473 ; 10.8 v 9.4 months , respectively ) . For cisplatin/pemetrexed , rates of grade 3 or 4 neutropenia , anemia , and thrombocytopenia ( P < or= .001 ) ; febrile neutropenia ( P = .002 ) ; and alopecia ( P < .001 ) were significantly lower , whereas grade 3 or 4 nausea ( P = .004 ) was more common . CONCLUSION In advanced NSCLC , cisplatin/pemetrexed provides similar efficacy with better tolerability and more convenient administration than cisplatin/gemcitabine . This is the first prospect i ve phase III study in NSCLC to show survival differences based on histologic type |
12,110 | 28,933,513 | Compared with control intervention , transcutaneous electrical nerve stimulation supplementation intervention was found to significantly reduce pain and morphine requirement over a period of 24 h and to promote functional recovery in patients who have undergone total knee arthroplasty | INTRODUCTION Transcutaneous electrical nerve stimulation is a possible adjunctive therapy to pharmacological treatment for controlling pain after total knee arthroplasty .
However , the results are controversial .
A systematic review and meta- analysis was conducted to explore the effect of transcutaneous electrical nerve stimulation on patients with total knee arthroplasty . | Transcutaneous electrical nerve stimulation ( TENS ) has been used to treat chronic pain syndromes and has been reported to be of some utility in the treatment of postsurgical pain . A r and omized , blinded , placebo-controlled trial was design ed to evaluate the utility of TENS after total knee arthroplasty . Patients were r and omly enrolled into patient-controlled anesthesia ( PCA ) alone , PCA plus TENS , or PCA plus sham TENS . The cumulative dose of morphine by PCA for each group was used as the end-point of the study . There was no significant reduction in the requirement for patient-controlled analgesia with or without TENS . We conclude that there is no utility for TENS in the postoperative management of pain after knee arthroplasty Abstract The influence of transcutaneous electrical stimulation ( TES ) and psychological factors in determining the intensity of acute postoperative pain was examined in a prospect i ve , double‐blind controlled trial completed by 30 patients having elective surgery . Psychometric tests were administered prior to surgery . Postoperative pain was assessed by cumulative morphine requirement ( M48 ) administered intramuscularly , and the mean score of a visual analogue scale of pain ( VAS ) , in the first 48 h following surgery . M48 was significantly correlated with the VAS score ( r = 0.62 , P < 0.001 ) , and with the psychometric test scores for trait‐anxiety ( r = 0.70 , P < 0.001 ) and neuroticism ( r = 0.67 , P < 0.001 ) . Though patients treated with TES required 25 % less morphine than those treated with placebo , the difference was not significant using monovariate analysis and applying unpaired two‐tailed Student 's t‐test ( P > 0.2 ) . When the contribution of neuroticism to the variance of M48 was adjusted using multiple regression analysis , the effect of TES became significant at the 0.05 level . Covariance analysis showed that TES contributed some 19 % to the explained variance of M48 while neuroticism contributed about 80 % , and there was no interaction between these two factors . These findings allow a degree of prediction of the individual patient 's postoperative pain and narcotic requirement , and point to a strong correlation between postoperative pain perception and personality Background Transcutaneous electrical nerve stimulation ( TENS ) is an effective adjunctive therapy for postoperative pain ; however , effects of different frequencies of stimulation have not been systematic ally investigated . Laparoscopic sterilization ( LS ) causes significant pain in the early postoperative period and requires substantial postoperative medication . Therefore , we studied the effects of TENS on postoperative pain after LS through placement of Yoon fallopian rings in a prospect i ve , r and omized , double-blinded , and placebo-controlled study . Methods Sixty-four patients undergoing LS for uterine tube ligation were r and omly allocated to receive either active TENS or placebo TENS . Postoperative pain was evaluated using a st and ard 11-point numeric rating scale and the McGill Pain Question naire (MPQ)-pain rating index and number of words chosen . Both high frequency ( 100 Hz ) and low frequency ( 4 Hz ) TENS , at strong , but comfortable sensory intensity , were applied for 20 minutes through 4 electrodes placed around the surgical incision immediately after surgery . Pain was assessed before and after application of TENS when patients were at postanesthesia care unit ( PACU ) . Results Both high and low frequency TENS significantly decreased postoperative pain intensity when compared with before administration of TENS using the numeric rating scale ( P=0.001 ) , pain rating index ( P=0.001 ) , and number of words chosen ( P=0.001 ) compared with placebo TENS ( P=0.001 ) . TENS in combination with st and ard pharmacologic analgesic treatment was efficacious for postoperative pain relief after LS . Conclusions We recommend regular use of multimodal therapy with TENS and analgesic drugs after LS with placement of Yoon rings Background and Objectives Continuous-infusion femoral nerve block ( FNB ) improves analgesia and rehabilitation after total knee replacement . In this study , we investigated the efficacy of single-injection FNB to achieve similar results . Methods A total of 30 patients were prospect ively and r and omly assigned to receive 40-mL injections of either 0.25 % bupivacaine ( group B ) or saline ( group S ) after total knee replacement . Blinded observers evaluated the patients for postoperative pain , morphine consumption , ambulating distances , and maximal knee flexion ; pain was scored on the visual analog scale ( VAS ) . Results Compared with group S patients , group B patients had significantly lower VAS pain scores ( P < .01 in the postoperative anesthesia care unit , P < .05 on the day after surgery ) ; group B patients also showed significantly lower total morphine use ( P < .05 ) and a lower incidence of morphine-related side effects . Significantly more group B than group S patients could ambulate on the day after surgery ( 93 % v 46 % , P < .05 ) , and mean ambulatory distance was significantly better for group B than group S patients at discharge ( 166 ± 37 v 117 ± 24 feet , P < .01 ) . Knee flexion was significantly better for group B than group S patients on the second day after surgery ( 70 ° v 60 ° , P < .01 ) , but the between-group difference was no longer statistically significant at discharge . Mean length of acute hospitalization was significantly shorter for group B ( 3 days ; range , 3 to 5 days ) than group S patients ( 4 days ; range , 3 to 6 days , P < .05 ) . Conclusions Single-injection FNB provided effective analgesia , facilitated early ambulation , and reduced the length of acute hospitalization in patients undergoing total knee replacement OBJECTIVE To investigate the possible effect of electric muscle stimulation ( EMS ) of the vastus medialis on the walking speed , Hospital for Special Surgery ( HSS ) knee score , and Physiological Cost Index ( PCI ) of patients during rehabilitation after total knee arthroplasty ( TKA ) . DESIGN Prospect i ve , r and omized controlled trial . SETTING Various departments at a district general hospital in the United Kingdom . PARTICIPANTS Thirty patients with unilateral osteoarthritis of the knee admitted for elective TKA were r and omly assigned to 1 of 2 groups ( 15 per group ) : control and treatment . Both groups received st and ard physical therapy . The treatment group also received EMS of the vastus medialis . INTERVENTION EMS ( 40Hz , 300micros ) of the vastus medialis muscle for 4 hours a day , starting on postoperative day 2 , over the first 6 postoperative weeks . MAIN OUTCOME MEASURES Changes in walking speed , HSS knee score , and effort of walking as measured by the PCI . RESULTS A statistically significant increase in walking speed was observed in the treatment group in relation to the control group at both 6 weeks ( P=.0002 ) and 12 weeks ( P<.0001 ) postoperatively . No statistically significant difference was observed in relation to the PCI or the HSS knee score variables . CONCLUSIONS Application of EMS after TKA result ed in a statistically significant improvement in patients ' walking speed . There was also a carry-over effect after the discontinuation of treatment BACKGROUND Transcutaneous electrical nerve stimulation ( TENS ) is regarded as an effective treatment for various types of pain . However , no r and omized controlled trial has investigated TENS on acupoints for postoperative analgesia in elderly patients . This study aim to investigate whether TENS on acupoints has any favorable effect on complementary analgesia after total hip arthroplasty ( THA ) for elderly patients compared with a sham control treatment . METHODS Sixty-eight elderly patients requiring THA surgery were enrolled and r and omly allocated to one of two groups . Group Acu received true TENS on acupoints ( bilateral P6 , L14 ; ST36 , GB31 ipsilateral to the surgery site ) and Group Sham received sham treatment . All patients received patient-controlled analgesia for two days postoperatively . Analgesia was assessed by postoperative fentanyl requirement and pain intensity using a visual analogue scale ( VAS-10 cm ) . The incidence of analgesia-related side effects , optional medication use and effects of patients ' blinding were recorded . RESULTS Fentanyl consumption in Group Acu was lower than that in Group Sham at 24 h ( mean ± SD ; 360±117 vs. 572±132 μg ; P<0.001 ) and 48 h ( 712±184 vs. 1022±197 μg ; P<0.001 ) after surgery . Postoperative pain intensity measured by VAS was similar in both groups . The incidence of opioid-related side effects and rescue medication for postoperative analgesia was significantly higher in Group Sham than in Group Acu . Differences between the groups regarding the effects of patients ' blinding were not significant . CONCLUSION TENS on specific acupoints is an effective and complementary approach to reduce postoperative analgesic requirement in elderly patients after THA OBJECTIVE To study the effects of transcutaneous electrical nerve stimulation on multimodal analgesia after total knee arthroplasty . METHODS Sixty patients diagnosed as knee osteoarthritis and suffered unilateral total knee arthroplasty in the department of orthopedics , Zhejiang Traditional Chinese Medicine Hospital from March 2009 to May 2012 were r and omly divided into control group and test group , 30 cases in each group . All the patients received celecoxib preoperatively , knee periarticular injection with the drug mixture intraoperatively , and celecoxib and morphine sulfate controlled-release tablets postoperatively . The patients in the test group were also treated with transcutaneous electrical nerve stimulation each day after operation . All the patients started doing functional exercises at 24 h after operation . Postoperative visual analogue scales(VAS ) , passive and active range of motion of knee joint , and complications were recorded . RESULTS The VAS scores of test group during postoperative 24 h to 1 week were 3.39 + /- 0.69 , 2.79 + /- 0.51 , 2.16 + /- 0.52 , and 1.07 + /- 0.57 separately , which were lower than 3.80 + /- 0.86 , 3.22 + /- 0.58 , 2.53 + /- 0.54 and 1.38 + /- 0.52 in the control group . The passive and active range of knee joint motion in the test group during postoperative 24 h to 2 weeks were ( 30.67 + /- 3.65 ) degrees , ( 39.17 + /- 3.96 ) degrees , ( 47.83 + /- 4.86 ) degrees , ( 93.67 + /- 7.30 ) degrees , ( 107.67 + /- 7.51 ) degrees and ( 29.83 + /- 5.33 ) degrees , ( 78.33 + /- 8.24 ) degrees , ( 95.17 + /- 5.94 ) degrees respectively , which were higher than ( 28.67 + /- 3.92 ) degrees , ( 36.83 + /- 4.25 ) degrees , ( 45.17 + /- 5.17 ) degrees , ( 89.83 + /- 7.25 ) degrees , ( 103.17 + /- 7.37 ) degrees and ( 24.17 + /- 10.26 ) degrees , ( 73.83 + /- 9.07 ) degrees , ( 91.33 + /- 7.42 ) degrees in the control group . In the test group , 19 patients had ring-shaped haemostasis impression to some extent in the skin of knee joint to different degree , and 5 patients had blister formation . CONCLUSION It is meaningful to apply transcutaneous electrical nerve stimulation for treating multimodal analgesia after total knee arthroplasty , which can not only relieve patients ' postoperative pain , and also promote the rehabilitation of knee function as far as possible OBJECTIVE Evaluate TENS effectiveness as a complementary treatment of chronic pelvic pain and deep dyspareunia in women with deep endometriosis . STUDY DESIGN This r and omized controlled trial was performed in a tertiary health care center , including twenty-two women with deep endometriosis undergoing hormone therapy with persistent pelvic pain and /or deep dyspareunia . This study was registered in the Brazilian Record of Clinical Trials ( ReBEC ) , under n RBR-3rndh6 . TENS application for 8 weeks followed a r and omized allocation into two groups : Group 1 - acupuncture-like TENS ( Frequency : 8Hz , pulse duration : 250μs ) - VIF ( n=11 ) and Group 2 - self-applied TENS ( Frequency : 85Hz , pulse duration : 75μs ) ( n=11 ) . The intensity applied was " strong , but comfortable " . We evaluated patients before and after treatment by the use of the Visual Analogue Scale , Deep Dyspareunia Scale and Endometriosis Quality of Life Question naire . We used the Wilcoxon and Mann-Whitney tests to compare before and after treatment conditions . RESULTS Despite the use of hormone therapy for 1.65±2.08 years , the 22 women with deep endometriosis sustained pelvic pain complaints ( VAS=5.95±2.13 and 2.45±2.42 , p<.001 ) and /or deep dyspareunia ( DDS=2.29±0.46 and 1.20±1.01 , p=.001 ) . We observed significant improvement for chronic pelvic pain , deep dyspareunia and quality of life by the use of TENS . Both application types of TENS were effective for improving the evaluated types of pain . CONCLUSIONS Both re sources ( acupuncture-like TENS and self-applied TENS ) demonstrated effectiveness as a complementary treatment of pelvic pain and deep dyspareunia , improving quality of life in women with deep endometriosis regardless of the device used for treatment |
12,111 | 25,278,038 | Survival of the control arm has frequently been underestimated in recent EOC RP3 trials .
Underestimating the outcome of the control arm may result in trials being underpowered to demonstrate the absolute benefit they were design ed to show | BACKGROUND The anticipated clinical outcome of the st and ard/control arm is an important parameter in the design of r and omized phase 3 ( RP3 ) trials to properly calculate sample size , power , and study duration .
Changing patterns of care or variation in the study population enrolled may lead to a deviation from the initially anticipated outcome .
The authors hypothesized that recent changes in patterns of care in epithelial ovarian cancer ( EOC ) have led to challenges in correctly estimating the outcome of control groups . | BACKGROUND Angiogenesis plays a role in the biology of ovarian cancer . We examined the effect of bevacizumab , the vascular endothelial growth factor inhibitor , on survival in women with this disease . METHODS We r and omly assigned women with ovarian cancer to carboplatin ( area under the curve , 5 or 6 ) and paclitaxel ( 175 mg per square meter of body-surface area ) , given every 3 weeks for 6 cycles , or to this regimen plus bevacizumab ( 7.5 mg per kilogram of body weight ) , given concurrently every 3 weeks for 5 or 6 cycles and continued for 12 additional cycles or until progression of disease . Outcome measures included progression-free survival , first analyzed per protocol and then up date d , and interim overall survival . RESULTS A total of 1528 women from 11 countries were r and omly assigned to one of the two treatment regimens . Their median age was 57 years ; 90 % had epithelial ovarian cancer , 69 % had a serous histologic type , 9 % had high-risk early-stage disease , 30 % were at high risk for progression , and 70 % had stage IIIC or IV ovarian cancer . Progression-free survival ( restricted mean ) at 36 months was 20.3 months with st and ard therapy , as compared with 21.8 months with st and ard therapy plus bevacizumab ( hazard ratio for progression or death with bevacizumab added , 0.81 ; 95 % confidence interval , 0.70 to 0.94 ; P=0.004 by the log-rank test ) . Nonproportional hazards were detected ( i.e. , the treatment effect was not consistent over time on the hazard function scale ) ( P<0.001 ) , with a maximum effect at 12 months , coinciding with the end of planned bevacizumab treatment and diminishing by 24 months . Bevacizumab was associated with more toxic effects ( most often hypertension of grade 2 or higher ) ( 18 % , vs. 2 % with chemotherapy alone ) . In the up date d analyses , progression-free survival ( restricted mean ) at 42 months was 22.4 months without bevacizumab versus 24.1 months with bevacizumab ( P=0.04 by log-rank test ) ; in patients at high risk for progression , the benefit was greater with bevacizumab than without it , with progression-free survival ( restricted mean ) at 42 months of 14.5 months with st and ard therapy alone and 18.1 months with bevacizumab added , with respective median overall survival of 28.8 and 36.6 months . CONCLUSIONS Bevacizumab improved progression-free survival in women with ovarian cancer . The benefits with respect to both progression-free and overall survival were greater among those at high risk for disease progression . ( Funded by Roche and others ; ICON7 Controlled-Trials.com number , IS RCT N91273375 . ) Investigators should properly calculate sample sizes before the start of their r and omised trials and adequately describe the details in their published report . In these a-priori calculations , determining the effect size to detect -- eg , event rates in treatment and control groups -- reflects inherently subjective clinical judgments . Furthermore , these judgments greatly affect sample size calculations . We question the br and ing of trials as unethical on the basis of an imprecise sample size calculation process . So-called underpowered trials might be acceptable if investigators use method ological rigor to eliminate bias , properly report to avoid misinterpretation , and always publish results to avert publication bias . Some shift of emphasis from a fixation on sample size to a focus on method ological quality would yield more trials with less bias . Unbiased trials with imprecise results trump no results at all . Clinicians and patients deserve guidance now PURPOSE The objective of this study was to compare the efficacy and safety of trabectedin plus pegylated liposomal doxorubicin ( PLD ) with that of PLD alone in women with recurrent ovarian cancer after failure of first-line , platinum-based chemotherapy . PATIENTS AND METHODS Women > or = 18 years , stratified by performance status ( 0 to 1 v 2 ) and platinum sensitivity , were r and omly assigned to receive an intravenous infusion of PLD 30 mg/m(2 ) followed by a 3-hour infusion of trabectedin 1.1 mg/m(2 ) every 3 weeks or PLD 50 mg/m(2 ) every 4 weeks . The primary end point was progression-free survival ( PFS ) by independent radiology assessment . RESULTS Patients ( N = 672 ) were r and omly assigned to trabectedin/PLD ( n = 337 ) or PLD ( n = 335 ) . Median PFS was 7.3 months with trabectedin/PLD v 5.8 months with PLD ( hazard ratio , 0.79 ; 95 % CI , 0.65 to 0.96 ; P = .0190 ) . For platinum-sensitive patients , median PFS was 9.2 months v 7.5 months , respectively ( hazard ratio , 0.73 ; 95 % CI , 0.56 to 0.95 ; P = .0170 ) . Overall response rate ( ORR ) was 27.6 % for trabectedin/PLD v 18.8 % for PLD ( P = .0080 ) ; for platinum-sensitive patients , it was 35.3 % v 22.6 % ( P = .0042 ) , respectively . ORR , PFS , and overall survival among platinum-resistant patients were not statistically different . Neutropenia was more common with trabectedin/PLD . Grade 3 to 4 transaminase elevations were also more common with the combination but were transient and noncumulative . H and -foot syndrome and mucositis were less frequent with trabectedin/PLD than with PLD alone . CONCLUSION When combined with PLD , trabectedin improves PFS and ORR over PLD alone with acceptable tolerance in the second-line treatment of recurrent ovarian cancer PURPOSE To compare the safety and efficacy of carboplatin and paclitaxel administered with or without the multidrug resistance modulator valspodar ( PSC 833 ) in untreated patients with advanced ovarian or primary peritoneal cancer . PATIENTS AND METHODS Seven hundred sixty-two patients with stage IV or suboptimally debulked stage III ovarian or primary peritoneal cancer were r and omly assigned to receive either valspodar 5 mg/kg every 6 hours for 12 doses , paclitaxel 80 mg/m(2 ) , and carboplatin area under the curve ( AUC ) 6 ( PC-PSC ; n = 381 ) or paclitaxel 175 mg/m(2 ) and carboplatin AUC 6 ( PC ; n = 381 ) . Time to disease progression ( TTP ) was the primary end point . Secondary end points were overall survival time ( OS ) , response rate ( RR ) , safety , and tolerability . RESULTS With a median follow-up of 736 days ( range , 1 to 2,280 days ) , the median TTP was 13.2 and 13.5 months in the PC-PSC and PC groups , respectively ( P = .67 ) ; the median OS was 32 and 28.9 months , respectively ( P = .94 ) . The overall RR was higher in the PC group ( 41.5 % v 33.6 % ; P = .02 ) . Central and peripheral nervous system and GI toxicities were more common in the PC-PSC group . Ataxia occurred in 53.5 % and 3.2 % of PC-PSC- and PC-treated patients , respectively . Febrile neutropenia occurred more frequently in the PC-PSC group . More PC-PSC-treated patients discontinued therapy because of adverse events ( AEs ) , experienced serious AEs , and required paclitaxel dose reductions . CONCLUSION The addition of valspodar to PC did not improve TTP or OS and was more toxic compared with PC in untreated patients with advanced ovarian or primary peritoneal cancer LBA1 Background : BEV , a humanized anti-VEGF monoclonal antibody , has demonstrated single-agent activity in patients with recurrent EOC , or PPC . The therapeutic impact of concurrent ± maintenance BEV with st and ard chemotherapy ( CT ) was evaluated in an international , double-blind , placebo-controlled phase III trial . METHODS Eligible patients had newly diagnosed , previously untreated EOC , PPC or FTC following abdominal surgery for staging and maximal effort at tumor debulking ; stage III ( macroscopic residual disease ) or stage IV disease . The r and omly allocated regimens were ( 1 ) CT ( IV paclitaxel 175 mg/m2 + carboplatin AUC 6 cycles 1 - 6 ) + placebo cycles (C)2 - 22 ( R1 ) ( 2 ) CT + concurrent BEV ( 15 mg/kg ) C2 - 6 + placebo C7 - 22 ( R2 ) ( 3 ) CT + concurrent BEV C2 - 6 + maintenance BEV C7 - 22 ( R3 ) Infusions were administered d1 of a 21d cycle . The primary endpoint is progression-free survival ( PFS ) ( radiographic , CA125 , clinical criteria or death ) ; secondary endpoints include overall survival , safety , and QoL. RESULTS 1,873 patients , median age 60 , were enrolled from 9/05 - 6/09 . Stage III optimally debulked ( 34 % ) , stage III sub-optimally debulked ( 40 % ) , and stage IV ( 26 % ) patients were similarly distributed in each treatment group . Grade 3 - 4 hypertension was reported in 1.6 % ( R1 ) , 5.4 % ( R2 ) , and 10.0 % ( R3 ) . Grade ≥ 3 GI perforation , hemorrhage or fistula occurred in 0.8 % ( R1 ) , 2.6 % ( R2 ) and 2.3 % ( R3 ) . Relative to R1 , the hazard of first progression or death for R2 was 0.908 ( 95 % CI : 0.795 - 1.04 , p=0.16 ) and for R3 was 0.717 ( 95 % CI : 0.625 - 0.824 , p<0.0001 ) . CONCLUSIONS This study demonstrates that front-line treatment of EOC , PPC , and FTC patients with CT plus concurrent and maintenance BEV prolongs PFS . This is the first anti-angiogenic agent to demonstrate benefit in this population . [ Table : see text ] PURPOSE To determine the side effects and feasibility of cisplatin and carboplatin each in combination with paclitaxel as front-line therapy in advanced epithelial ovarian cancer . PATIENTS AND METHODS Patients were r and omly allocated to receive paclitaxel 175 mg/m(2 ) intravenously as a 3-hour infusion followed by either cisplatin 75 mg/m(2 ) or carboplatin ( area under the plasma concentration-time curve of 5 ) , both on day 1 . The schedule was repeated every 3 weeks for at least six cycles . Women allocated to paclitaxel-cisplatin were admitted to the hospital , whereas the carboplatin regimen was administered to out patients . RESULTS A total of 208 eligible patients were r and omized . Both regimens could be delivered in an optimal dose and without significant delay . Paclitaxel-carboplatin produced significantly less nausea and vomiting ( P : < .01 ) and less peripheral neurotoxicity ( P : = .04 ) but more granulocytopenia and thrombocytopenia ( P : < .01 ) . The overall response rate in 132 patients with measurable disease was 64 % ( 84 of 132 patients ) , and in patients with elevated CA 125 levels at start , it was 74 % ( 132 of 178 patients ) . With a median follow-up time of 37 months , the median progression-free survival time of all patients was 16 months and the median overall survival time was 31 months . The small number of patients entered onto the study caused wide confidence intervals ( CIs ) around the hazards ratio for progression-free survival of paclitaxel-carboplatin compared with paclitaxel-cisplatin ( hazards ratio , 1.07 ; 95 % CI , 0.78 to 1.48 ) and did not allow conclusions about efficacy . CONCLUSION Paclitaxel-carboplatin is a feasible regimen for out patients with ovarian cancer and has a better toxicity profile than paclitaxel-cisplatin PURPOSE To analyze the effect of different doses of paclitaxel with fixed doses of carboplatin in the treatment of ovarian cancer . PATIENTS AND METHODS Patients with histologically confirmed epithelial ovarian cancer , International Federation of Gynecology and Obstetrics stages IIB to IV , were eligible for this r and omized , multicenter study . Women were r and omly assigned to treatment with ( 1 ) carboplatin at the dose ( in milligrams ) corresponding to the following formula : target area under the free carboplatin plasma concentration versus time curve ( AUC ) = 6 x ( glomerular filtration rate + 25 ) mg/m(2 ) ( AUC6 ) plus paclitaxel 175 mg/m(2 ) for six cycles every 21 days or ( 2 ) carboplatin AUC6 plus paclitaxel 225 mg/m(2 ) for six cycles every 21 days . A total of 502 women entered the study . RESULTS Pathologic complete response was documented in 132 patients ( 63.8 % ) in the 175 mg/m(2 ) group and in 127 cases ( 55.7 % ) in the 225 mg/m(2 ) group ( chi(2 ) P = .090 ) . The 4-year progression-free survival rate was 41.5 % ( SE = 3.5 ) in the 175-mg group and 39.2 % ( SE = 3.5 ) in the 225-mg group . The corresponding 4-year survival rates were 46.2 % ( based on 115 deaths ) and 47.3 % ( based on 113 deaths ) , respectively . CONCLUSION This r and omized trial suggests that paclitaxel 175 mg/m(2 ) plus carboplatin AUC6 is the schedule with a more favorable profile than paclitaxel 225 mg/m(2 ) plus carboplatin AUC6 BACKGROUND Topotecan has single-agent activity in recurrent ovarian cancer . It was evaluated in a novel combination compared with st and ard frontline therapy . METHODS Women aged 75 years or younger with newly diagnosed stage IIB or greater ovarian cancer , Eastern Cooperative Oncology Group Performance Status of 1 or less , were stratified by type of primary surgery and residual disease , treatment center , and age ; then r and omly assigned to one of the two 21-day intravenous regimens . Patients in arm 1 ( n = 409 ) were administered four cycles of cisplatin 50 mg/m(2 ) on day 1 and topotecan 0.75 mg/m(2 ) on days 1 - 5 , then four cycles of paclitaxel 175 mg/m(2 ) over 3 hours on day 1 followed by carboplatin ( area under the curve = 5 ) on day 1 . Patients in arm 2 ( n = 410 ) were given paclitaxel plus carboplatin as in arm 1 for eight cycles . We compared progression-free survival ( PFS ) , overall survival , and cancer antigen-125 normalization rates in the two treatment arms . A stratified log-rank test was used to assess the primary endpoint , PFS . All statistical tests were two-sided . RESULTS A total of 819 patients were r and omly assigned . At baseline , the median age of the patients was 57 years ( range = 28 - 78 ) ; 81 % had received debulking surgery , and of these , 55 % had less than 1 cm residual disease ; 66 % of patients were stage III and 388 ( 47.4 % ) patients had measurable disease . After a median follow-up of 43 months , 650 patients had disease progression or died without documented progression and 406 had died . Patients in arm 1 had more hematological toxicity and hospitalizations than patients in arm 2 ; PFS was 14.6 months in arm 1 vs 16.2 months in arm 2 ( hazard ratio = 1.10 , 95 % confidence interval = 0.94 to 1.28 , P = .25 ) . Among patients with elevated baseline cancer antigen-125 , fewer in arm 1 than in arm 2 had levels return to normal by 3 months after r and om assignment ( 51.6 % vs 63.3 % , P = .007 ) CONCLUSIONS Topotecan and cisplatin , followed by carboplatin and paclitaxel , were more toxic than carboplatin and paclitaxel alone , but without improved efficacy . Carboplatin plus paclitaxel remains the st and ard of care for advanced epithelial ovarian cancer BACKGROUND Serum CA125 concentration often rises several months before clinical or symptomatic relapse in women with ovarian cancer . In the MRC OV05/EORTC 55955 collaborative trial , we aim ed to establish the benefits of early treatment on the basis of increased CA125 concentrations compared with delayed treatment on the basis of clinical recurrence . METHODS Women with ovarian cancer in complete remission after first-line platinum-based chemotherapy and a normal CA125 concentration were registered for this r and omised controlled trial . Clinical examination and CA125 measurement were done every 3 months . Patients and investigators were masked to CA125 results , which were monitored by coordinating centres . If CA125 concentration exceeded twice the upper limit of normal , patients were r and omly assigned ( 1:1 ) by minimisation to early or delayed chemotherapy . Patients and clinical sites were informed of allocation to early treatment , and treatment was started as soon as possible within 28 days of the increased CA125 measurement . Patients assigned to delayed treatment continued masked CA125 measurements , with treatment commencing at clinical or symptomatic relapse . All patients were treated according to st and ard local practice . The primary outcome was overall survival . Analysis was by intention to treat . This study is registered , IS RCT N87786644 . FINDINGS 1442 patients were registered for the trial , of whom 529 were r and omly assigned to treatment groups and were included in our analysis ( 265 early , 264 delayed ) . With a median follow-up of 56·9 months ( IQR 37·4 - 81·8 ) from r and omisation and 370 deaths ( 186 early , 184 delayed ) , there was no evidence of a difference in overall survival between early and delayed treatment ( HR 0·98 , 95 % CI 0·80 - 1·20 , p=0·85 ) . Median survival from r and omisation was 25·7 months ( 95 % CI 23·0 - 27·9 ) for patients on early treatment and 27·1 months ( 22·8 - 30·9 ) for those on delayed treatment . INTERPRETATION Our findings showed no evidence of a survival benefit with early treatment of relapse on the basis of a raised CA125 concentration alone , and therefore the value of routine measurement of CA125 in the follow-up of patients with ovarian cancer who attain a complete response after first-line treatment is not proven . FUNDING UK Medical Research Council and the European Organisation for Research and Treatment of Cancer PURPOSE We aim ed at investigating the efficacy , tolerability , and quality of life ( QOL ) of gemcitabine ( GEM ) compared with pegylated liposomal doxorubicin ( PLD ) in the salvage treatment of recurrent ovarian cancer . PATIENTS AND METHODS A phase III r and omized multicenter trial was planned to compare GEM ( 1,000 mg/m(2 ) on days 1 , 8 , and 15 every 28 days ) with PLD ( 40 mg/m(2 ) every 28 days ) in ovarian cancer patients who experienced treatment failure with only one platinum/paclitaxel regimen and who experienced recurrence or progression within 12 months after completion of primary treatment . RESULTS One hundred fifty-three patients were r and omly assigned to PLD ( n = 76 ) or GEM ( n = 77 ) . Treatment arms were well balanced for clinicopathologic characteristics . Grade 3 or 4 neutropenia was more frequent in GEM-treated patients versus PLD-treated patients ( P = .007 ) . Grade 3 or 4 palmar-plantar erythrodysesthesia was documented in a higher proportion of PLD patients ( 6 % ) versus GEM patients ( 0 % ; P = .061 ) . The overall response rate was 16 % in the PLD arm compared with 29 % in the GEM arm ( P = .056 ) . No statistically significant difference in time to progression ( TTP ) curves according to treatment allocation was documented ( P = .411 ) . However , a trend for more favorable overall survival was documented in the PLD arm compared with the GEM arm , although the P value was of borderline statistical significance ( P = .048 ) . Statistically significantly higher global QOL scores were found in PLD-treated patients at the first and second postbaseline QOL assessment s. CONCLUSION GEM does not provide an advantage compared with PLD in terms of TTP in ovarian cancer patients who experience recurrence within 12 months after primary treatment but should be considered in the spectrum of drugs to be possibly used in the salvage setting A r and omised phase III trial was conducted to assess the role of interferon-alpha ( INFα ) 2a as maintenance therapy following surgery and /or chemotherapy in patients with epithelial ovarian carcinoma . Patients were r and omised following initial surgery/chemotherapy to interferon-alpha 2a as 4.5 mega-units subcutaneously 3 days per week or to no further treatment . A total of 300 patients were r and omised within the study between February 1990 and July 1997 . No benefit for interferon maintenance was seen in terms of either overall or clinical event-free survival . We conclude that INF-α is not effective as a maintenance therapy in the management of women with ovarian cancer . The need for novel therapeutics or strategies to prevent the almost inevitable relapse of patients despite increasingly effective surgery and chemotherapy remains BACKGROUND The majority of patients with ovarian cancer are not cured by first-line treatment . Until now , no study could demonstrate any substantial benefit when exposing ovarian cancer patients to second-line chemotherapy . However , most treatment regimens induce toxicity , thus negatively influencing the quality of rather limited life spans . Here we evaluate whether a second-line chemotherapy can offer any benefit compared with a less toxic hormonal treatment . PATIENTS AND METHODS Patients with ovarian cancer progressing during platinum-paclitaxel containing first-line therapy or experiencing relapse within 6 months were eligible . Patients were stratified for response to primary treatment ( progression versus no change/response ) , and measurable versus non-measurable disease . Treatment consisted of either treosulfan 7 g/m5 infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or intramuscularly . Both regimens were repeated every 4 weeks . RESULTS This study began in late 1996 , and after 2.5 years accrual an interim analysis was performed when several investigators reported their concern about a suspected lack of efficacy . Following this analysis the recruitment was stopped early and the 78 patients already enrolled were followed up . The majority of patients received treatment until progressive disease was diagnosed or death occurred . Treatment delay was observed rarely and dose reduction was performed only in the treosulfan arm in 5 % of 150 courses . Overall , both treatment arms were well tolerated . No objective responses were observed . The median survival time was 36 and 30 weeks in the treosulfan and leuprorelin arms , respectively . Overall survival did not differ between patients with relapse 3 - 6 months after first-line chemotherapy compared with patients with progressive disease within 3 months . CONCLUSIONS The selected patient population represents a subgroup with extremely poor prognosis . Accordingly , results were not impressive . Both treatment arms showed favourable toxicity data , but failed to show remarkable activity , thus adding only limited evidence to the issue of whether patients with refractory ovarian cancer might benefit from second-line chemotherapy . Even stratified analysis did not identify any subgroup of patients in whom the administration of second-line chemotherapy could demonstrate a clinical ly relevant survival benefit OBJECTIVE Because debate continues over the role of combination , platinum-based chemotherapy for platinum-sensitive ( PS ) , recurrent ovarian cancer ( OC ) , we compared overall survival ( OS ) , progression-free survival ( PFS ) , confirmed complete response rate and time to treatment failure in this population . METHODS Patients with recurrent stage III or IV OC , a progression-free and platinum-free interval of 6 - 24 months after first-line platinum-based chemotherapy and up to 12 courses of a non-platinum containing consolidation treatment were eligible . Patients were r and omized to i.v . pegylated liposomal doxorubicin ( PLD ) ( 30 mg/m2 ) plus i.v . carboplatin ( AUC=5 mg/mL min ) once every 4 weeks ( PLD arm ) or i.v . carboplatin alone ( AUC=5 mg/mL min ) once every 4 weeks . RESULTS The PLD arm enrolled 31 patients and the carboplatin alone arm 30 for a total of 61 patients out of 900 planned . Response rates were 67 % for the PLD arm and 32 % for the carboplatin only arm ( Fisher 's exact p=0.02 ) . The estimated median PFS was 12 and 8 months for PLD versus carboplatin alone . The estimated median OS on the PLD arm was 26 months and 18 months on the carboplatin only arm ( p=0.02 ) . Twenty-six percent of the patients on the PLD arm reported grade 4 toxicities , all hematological in nature . CONCLUSION This study was closed early because of slow patient accrual . The response rate , median PFS and OS results are intriguing . These data suggest that there may be an advantage to the PLD plus carboplatin combination treatment in patients with PS , recurrent OC . The regimen should be further tested A prospect i ve r and omized study was conducted in women with suboptimal ( > 3 cm residual ) Stage III , Stage IV , and recurrent ovarian adenocarcinoma to determine if combination chemotherapy is more effective than melphalan alone in achieving remission and improving survival . Of 233 evaluable patients with measurable disease , there were 64 treated with melphalan alone , of whom 20 % achieved a clinical complete response and 17 % , a partial response . Of the 97 patients receiving melphalan plus hexamethylmelamine , 28 % achieved complete response compared with 32 % of 72 patients given Adriamycin plus cyclophosphamide . The partial response rates for the combinations were 24 % and 17 % , respectively . The effect of these treatments was assessed in an additional 136 evaluable patients without measurable disease by progression‐free interval and duration of survival . After statistically adjusting for distribution of cell type and grade , the clinical complete response rate for Adriamycin and cyclophosphamide ( 32 % ) in measurable cases was significantly higher ( P = 0.04 ) than for melphalan alone . However , this combination did not improve median survival ( 12.3 , 13.5 , and 14.2 months , respectively , for M , M + H , and A + C ) . None of the other parameters showed a statistically significant advantage for combination chemotherapy , but the combinations caused more hematologic and gastrointestinal toxicity BACKGROUND Paclitaxel and carboplatin given every 3 weeks is st and ard treatment for advanced ovarian carcinoma . Attempts to improve patient survival by including other drugs have yielded disappointing results . We compared a conventional regimen of paclitaxel and carboplatin with a dose-dense weekly regimen in women with advanced ovarian cancer . METHODS Patients with stage II to IV epithelial ovarian cancer , fallopian tube cancer , or primary peritoneal cancer were eligible for enrolment in this phase 3 , open-label , r and omised controlled trial at 85 centres in Japan . Patients were r and omly assigned by computer-generated r and omisation sequence to receive six cycles of either paclitaxel ( 180 mg/m(2 ) ; 3-h intravenous infusion ) plus carboplatin ( area under the curve [ AUC ] 6 mg/mL per min ) , given on day 1 of a 21-day cycle ( conventional regimen ; n=320 ) , or dose-dense paclitaxel ( 80 mg/m(2 ) ; 1-h intravenous infusion ) given on days 1 , 8 , and 15 plus carboplatin given on day 1 of a 21-day cycle ( dose-dense regimen ; n=317 ) . The primary endpoint was progression-free survival . Analysis was by intention to treat ( ITT ) . This trial is registered with Clinical Trials.gov , number NCT00226915 . FINDINGS 631 of the 637 enrolled patients were eligible for treatment and were included in the ITT population ( dose-dense regimen , n=312 ; conventional regimen , n=319 ) . Median progression-free survival was longer in the dose-dense treatment group ( 28.0 months , 95 % CI 22.3 - 35.4 ) than in the conventional treatment group ( 17.2 months , 15.7 - 21.1 ; hazard ratio [ HR ] 0.71 ; 95 % CI 0.58 - 0.88 ; p=0.0015 ) . Overall survival at 3 years was higher in the dose-dense regimen group ( 72.1 % ) than in the conventional treatment group ( 65.1 % ; HR 0.75 , 0.57 - 0.98 ; p=0.03 ) . 165 patients assigned to the dose-dense regimen and 117 assigned to the conventional regimen discontinued treatment early . Reasons for participant dropout were balanced between the groups , apart from withdrawal because of toxicity , which was higher in the dose-dense regimen group than in the conventional regimen group ( n=113 vs n=69 ) . The most common adverse event was neutropenia ( dose-dense regimen , 286 [ 92 % ] of 312 ; conventional regimen , 276 [ 88 % ] of 314 ) . The frequency of grade 3 and 4 anaemia was higher in the dose-dense treatment group ( 214 [ 69 % ] ) than in the conventional treatment group ( 137 [ 44 % ] ; p<0.0001 ) . The frequencies of other toxic effects were similar between groups . INTERPRETATION Dose-dense weekly paclitaxel plus carboplatin improved survival compared with the conventional regimen and represents a new treatment option in women with advanced epithelial ovarian cancer . FUNDING Bristol-Myers Squibb OBJECTIVE BAY 12 - 9566 ( tanomastat ) is a biphenyl matrix metalloprotease inhibitor ( MMPI ) with antiangiogenic and antimetastatic properties in vivo . The objective of the study was to determine whether the addition of BAY 12 - 9566 after optimal response to chemotherapy could improve time to progression ( TTP ) . PATIENTS AND METHODS Patients enrolled in the study had received 6 - 9 cycles of platinum/paclitaxel containing chemotherapy for stage III or IV ovarian carcinoma , with a response of no evidence of disease , or complete or partial response with residual disease < 2 cm . Patients were then r and omized to BAY 12 - 9566 800 mg p.o . b.i.d . or placebo . The primary endpoint was progression-free survival ( PFS ) ; secondary endpoints were quality of life , toxicity , changes in CA 125 levels , response , and overall survival ( OS ) . The total planned sample size was 730 . RESULTS The study was closed after 243 patients had been r and omized because of Bayer 's decision to close all ongoing trials due to negative results from other phase III trials in pancreatic and small cell lung cancer . The final analysis was performed in August 2000 after the requisite number of events for the first planned interim analysis had occurred ; 54 % of patients had progressed and 18 % had died . PATIENT CHARACTERISTICS performance status was ECOG 0/1/2 in 65/33/2 % ; median age 57 years ; 79 % of patients were FIGO stage III ; 41 % were optimally debulked ; 76 % had serous histology , and 67 % had > or = grade 3 histology . Toxicity was generally grade 1 or 2 in severity , with the most common ( BAY 12 - 9566 vs. placebo ) being nausea ( 26 % vs. 13 % ) , fatigue ( 24 % vs. 12 % ) , diarrhea ( 14 % vs. 10 % ) , rash ( 12 % vs. 7 % ) , grade 3/4 thrombocytopenia ( 3 % vs. 1 % ) , and grade 3/4 anemia ( 5 % vs. 1 % ) . Median time to progression ( TTP ) was 10.4 months ( 8.5 - 11.5 ) for BAY 12 - 9566 and 9.2 months ( 7.2 - 13.9 ) for placebo ( P = 0.67 ) . Median overall survival ( OS ) was 13.9 months ( 12.9-infinity ) for BAY 12 - 9566 and 11.9 months ( 10.5 - 16.5 ) for placebo ( P = 0.53 ) . CONCLUSION We conclude that BAY 12 - 9566 was generally well tolerated and at the time of the final analysis , there was no evidence of an impact of BAY 12 - 9566 on PFS or OS OBJECTIVE The objective of this prospect i ve r and omized phase III trial was to compare paclitaxel plus carboplatin ( PC ) versus topotecan plus carboplatin and paclitaxel ( TPC ) in women with suboptimal stage III ( residual tumour > 1 cm ) or stage IV ovarian cancer to evaluate the survival rate and toxicities . METHODS Eligible for the study were patients aged at least 18 years old with histological/cytological diagnosis of FIGO stages III ( residual tumour ≥1 cm after primary surgery)--IV epithelial ovarian cancer . Patients were r and omized to iv PC on day 1 , every 21 days or iv topotecan daily for three days and PC on day 3 , every 21 days . RESULTS The intention to treat population was made of 326 patients in total , 170 in the PC group and 156 in the TPC group . The life table estimates of survival probabilities at one , three and five years were , respectively , 0.94 ( 95 % CI : 0.88 - 0.97 ) , 0.53 ( 95 % CI : 0.44 - 0.62 ) and 0.32 ( 95%CI : 0.23 - 0.42 ) in the PC group , and 0.92 ( 95 % CI : 0.86 - 0.95 ) , 0.52 ( 95 % CI : 0.42 - 0.61 ) , and 0.32(95%CI : 0.22 - 0.43 ) in the TPC group ( log-rank test at 5 years : ns ) . The results of the survival analysis based on Cox regression model showed no statistically significant differences between groups ( p-value : ns ) . The number of subjects with at least one event with possible relationship to study medication was 151 ( 88.8 % ) in the PC group and 139 ( 89.1 % ) in the TPC group ( p = ns ) . In the PC group , 79 patients ( 23.6 % ) experienced at least one Adverse Event ( AE ) grade d as severe and 16 patients ( 4.8 % ) at least one life-threatening AE , whilst in the TPC group , the number of patients who presented at least one severe or life-threatening AE was 86 ( 24 % ) and 37 ( 10.3 % ) , respectively . CONCLUSION The results of the present study show that the addition of topotecan to a st and ard paclitaxel/carboplatin regimen in the treatment of advanced epithelial ovarian cancer did not result in significant advantages in terms of survival rate . A slightly worse toxicity profile for TPC was observed PURPOSE Topotecan is an active second-line treatment for advanced ovarian cancer . Its efficacy as consolidation treatment after first-line st and ard chemotherapy is unknown . PATIENTS AND METHODS To investigate whether topotecan ( 1.5 mg/m(2 ) on days 1 through 5 , four cycles , every 3 weeks ) prolonged progression-free survival ( PFS ) for patients responding to st and ard carboplatin ( area under the curve 5 ) and paclitaxel ( 175 mg/m(2 ) administered as a 3-hour infusion in six cycles ; CP ) , a multicenter phase III study was performed with an 80 % power to detect a 50 % prolongation of median PFS . Patients were registered at diagnosis and r and omized after the end of CP . RESULTS Two hundred seventy-three patients were r and omly assigned ( topotecan , n = 137 ; observation , n = 136 ) , with a median age of 56 years . Stage at diagnosis was advanced in three fourths of patients ( stage III in 65 % of patients ; stage IV in 10 % ) ; after primary surgery , 46 % had no residual disease and 20 % were optimally debulked . After CP , 87 % reached a clinical complete response , and 13 % achieved a partial response . Neutropenia ( grade 3/4 in 58 % of the patients ) and thrombocytopenia ( grade 3 in 21 % ; grade 4 in 3 % ) were the most frequent toxicities attributed to topotecan . There was no statistically significant difference in PFS between the arms ( P = .83 ; log-rank test ) : median PFS was 18.2 months in the topotecan arm and 28.4 in the control arm . Hazard ratio of progression for patients receiving topotecan was 1.18 ( 95 % CI , 0.86 to 1.63 ) after adjustment for residual disease , interval debulking surgery , and response to CP . CONCLUSION The present analysis indicates that consolidation with topotecan does not improve PFS for patients with advanced ovarian cancer who respond to initial chemotherapy with carboplatin and paclitaxel PURPOSE Although ovarian cancer is one of the most chemotherapy-sensitive solid tumors , cure after radical surgery and chemotherapy is uncommon . A r and omized trial comparing high-dose sequential chemotherapy with peripheral blood stem cell ( PBSC ) support with platinum-based combination chemotherapy was conducted to investigate whether dose-intensification improves outcome . PATIENTS AND METHODS One hundred forty-nine patients with untreated ovarian cancer were r and omly assigned after debulking surgery to receive st and ard combination chemotherapy or sequential high-dose ( HD ) treatment with two cycles of cyclophosphamide and paclitaxel followed by three cycles of HD carboplatin and paclitaxel with PBSC support . HD melphalan was added to the final cycle . The median age was 50 years ( range , 20 to 65 years ) and International Federation of Gynecology and Obstetrics stage was IIb/IIc in 4 % , III in 78 % , and IV in 17 % . RESULTS Seventy-six percent of patients received all five cycles in the HD arm and the main toxicities were neuro-/ototoxicity , gastrointestinal toxicity , and infection and one death from hemorrhagic shock . After a median follow-up of 38 months , the progression-free survival was 20.5 months in the st and ard arm and 29.6 months in the HD arm ( hazard ratio [ HR ] , 0.84 ; 95 % CI , 0.56 to 1.26 ; P , .40 ) . Median overall survival ( OS ) was 62.8 months in the st and ard arm and 54.4 months in the HD arm ( HR , 1.17 ; 95 % CI , 0.71 to 1.94 ; P , .54 ) . CONCLUSION This is the first r and omized trial comparing sequential HD versus st and ard dose chemotherapy in first-line treatment of patients with advanced ovarian cancer . We observed no statistically significant difference in progression-free survival or OS and conclude that HD chemotherapy does not appear to be superior to conventional dose chemotherapy BACKGROUND Whether progression-free survival ( PFS ) or overall survival ( OS ) is the more appropriate endpoint in clinical trials of metastatic cancer is controversial . In some disease and treatment setting s , an improvement in PFS does not result in an improved OS . METHODS We partitioned OS into two parts and expressed it as the sum of PFS and survival postprogression ( SPP ) . We simulated r and omized clinical trials with two arms that had respective medians for PFS of 6 and 9 months . We assumed no treatment difference in median SPP . We found the probability of a statistically significant benefit in OS for various median SPP and observed P values for PFS . We compared the sample sizes required for PFS vs OS for various median SPP . We compare our results with the literature regarding surrogacy of PFS for OS by use of the correlation between hazard ratios for PFS and OS . All statistical tests were two-sided . RESULTS For a trial with observed P value for improvement in PFS of .001 , there was a greater than 90 % probability for statistical significance in OS if median SPP was 2 months but less than 20 % if median SPP was 24 months . For a trial requiring 280 patients to detect a 3-month difference in PFS , 350 and 2440 patients , respectively , were required to have the same power for detecting a real difference in OS that is carried over from the 3-month benefit in PFS when the median SPP was 2 and 24 months . CONCLUSIONS Addressing SPP is important in underst and ing treatment effects . For clinical trials with a PFS benefit , lack of statistical significance in OS does not imply lack of improvement in OS , especially for diseases with long median SPP . Although there may be no treatment effect on SPP , its variability so dilutes the OS comparison that statistical significance is likely lost . OS is a reasonable primary endpoint when median SPP is short but is too high a bar when median SPP is long , such as longer than 12 months A r and omized clinical trial was conducted in women with bulky ( suboptimal ) Stage III and Stage IV ovarian carcinoma , using doxorubicin ( Adriamycin ) and cyclophosphamide with or without cisplatin . There were 440 evaluable cases , of which 227 had measurable disease . One hundred twenty of these latter patients were treated with cyclophosphamide and doxorubicin ( CA ) , while 107 received cyclophosphamide , doxorubicin and cisplatin ( CAP ) . The clinical complete response ( CR ) rate for CA was 26 % ( 31/120 ) compared with 51 % ( 55/107 ) for CAP ( P = < 0.0001 ) . Of 23 CRs receiving CA who had a second‐look laparotomy , only four were negative ; of 39 CRs receiving CAP and a second‐look , 13 were negative ( not statistically significant ) . The response duration for patients with measurable disease ( median 14.6 versus 8.8 months ) , progression‐free interval for all patients ( 13.1 versus 7.7 months ) , and survival for patients with measurable disease ( 19.7 versus 15.7 months ) showed a statistically significant advantage for CAP ; however , there was no difference in survival of patients with nonmeasurable disease . Toxicity was more severe with CAP but was tolerable . Thus , the addition of cisplatin improves the chemotherapy of advanced ovarian carcinoma OBJECTIVE Provide long-term follow-up data for women treated in a r and omized multicenter study of pegylated liposomal doxorubicin compared with topotecan . METHODS Patients with epithelial ovarian cancer that recurred after or failed to respond to first-line platinum-based chemotherapy were r and omized to receive pegylated liposomal doxorubicin 50 mg/m(2 ) every 28 days ( n = 239 ) or topotecan 1.5 mg/m(2 ) per day for 5 days every 21 days ( n = 235 ) . Patients were stratified prospect ively based on response to initial platinum-based chemotherapy as well as the presence or absence of bulky disease . Most patients had been previously treated with platinum and taxanes ( 74 % in the pegylated liposomal doxorubicin group and 72 % in the topotecan group ) . Survival data are mature : 87 % of patients have died ( n = 413 ) . RESULTS There was an 18 % reduction in the risk of death for patients treated with pegylated liposomal doxorubicin ( median survival 62.7 weeks for pegylated liposomal doxorubicin and 59.7 weeks for topotecan-treated patients ; HR = 1.216 ; 95 % confidence interval ( CI ) 1.000 - 1.478 ; P = 0.050 ) . The hazard ratio for all r and omized subjects ( includes those r and omized , but never treated ; n = 481 ) was 1.23 ( median survival 63.6 weeks for pegylated liposomal doxorubicin and 57.0 weeks for topotecan-treated patients ; 95 % CI 1.01 - 1.50 ; P = 0.038 ) . For patients with platinum-sensitive disease , there was a 30 % reduction in the risk of death for the pegylated liposomal doxorubicin-treated group ( median survival 107.9 weeks for pegylated liposomal doxorubicin and 70.1 weeks for topotecan-treated patients ; HR = 1.432 ; 95 % CI 1.066 - 1.923 ; P = 0.017 ) . In patients with platinum-refractory disease , survival was similar between treatment groups . CONCLUSION Long-term follow-up demonstrates that treatment with pegylated liposomal doxorubicin significantly prolongs survival compared with topotecan in patients with recurrent and refractory epithelial ovarian cancer . The survival benefit is pronounced in patients with platinum-sensitive disease PURPOSE This study was undertaken to assess if prolonged paclitaxel administration in combination with cisplatin improves overall survival ( OS ) in epithelial ovarian cancer ( EOC ) . PATIENTS AND METHODS Eligible patients with suboptimal stage III or IV EOC , fallopian tube , or primary peritoneal cancer were r and omly allocated to receive six cycles of cisplatin 75 mg/m2 and either paclitaxel 135 mg/m2 during 24 hours ( arm 1 ) or paclitaxel 120 mg/m2 during 96 hours ( arm 2 ) . RESULTS Planned accrual was 324 patients ; 293 were enrolled before the study was closed as a result of a scheduled interim futility analysis . There were 13 ineligible patients ; thus , 140 patients in each arm were assessable . In arm 1 , 80 % of patients completed all six cycles compared with 83 % of patients in arm 2 . Grade 4 granulocytopenia was more common in arm 1 ( 79 % v 54 % ; P < .001 ) whereas grade 3 or worse anemia was more severe in arm 2 ( 6 % v 18 % ; P < .003 ) . The median progression-free survival was 1.03 years for arm 1 versus 1.05 years for arm 2 . The median OS was 2.49 and 2.54 years for arms 1 and 2 , respectively . There have been 237 reported deaths . The relative death rate was approximately 12 % greater in arm 2 ( hazard ratio , 1.12 ; 95 % CI , 0.860 to 1.45 ) . CONCLUSION Patients with advanced EOC have a relatively poor prognosis . The results of treatment with cisplatin and paclitaxel are not significantly improved by prolonging the paclitaxel infusion from 24 to 96 hours BACKGROUND Chemotherapy with a platinum agent and a taxane ( paclitaxel ) is considered the st and ard of care for treatment of ovarian carcinoma . We compared the combination of docetaxel-carboplatin with the combination of paclitaxel-carboplatin as first-line chemotherapy for stage Ic-IV epithelial ovarian or primary peritoneal cancer . METHODS We r and omly assigned 1077 patients to receive docetaxel at 75 mg/m2 of body surface area ( 1-hour intravenous infusion ) or paclitaxel at 175 mg/m2 ( 3-hour intravenous infusion ) . Both treatments then were followed by carboplatin to an area under the plasma concentration-time curve of 5 . The treatments were repeated every 3 weeks for six cycles ; in responding patients , an additional three cycles of single-agent carboplatin was permitted . Survival curves were calculated by the Kaplan-Meier method , and hazard ratios were estimated with the Cox proportional hazards model . All statistical tests were two-sided . RESULTS After a median follow-up of 23 months , both groups had similar progression-free survival ( medians of 15.0 months for docetaxel-carboplatin and 14.8 months for paclitaxel-carboplatin ; hazard ratio [ HR ] docetaxel-paclitaxel = 0.97 , 95 % confidence interval [ CI ] = 0.83 to 1.13 ; P = .707 ) , overall survival rates at 2 years ( 64.2 % and 68.9 % , respectively ; HR = 1.13 , 95 % CI = 0.92 to 1.39 ; P = .238 ) , and objective tumor ( 58.7 % and 59.5 % , respectively ; difference between docetaxel and paclitaxel = -0.8 % , 95 % CI = -8.6 % to 7.1 % ; P = .868 ) and CA-125 ( 75.8 % and 76.8 % , respectively ; difference docetaxel-paclitaxel = -1.0 % , 95 % CI = -7.2 % to 5.1 % ; P = .794 ) response rates . However , docetaxel-carboplatin was associated with substantially less overall and grade 2 or higher neurotoxicity than paclitaxel-carboplatin ( grade > or = 2 neurosensory toxicity in 11 % versus 30 % , difference = 19 % , 95 % CI = 15 % to 24 % ; P<.001 ; grade > or = 2 neuromotor toxicity in 3 % versus 7 % , difference = 4 % , 95 % CI = 1 % to 7 % ; P<.001 ) . Treatment with docetaxel-carboplatin was associated with statistically significantly more grade 3 - 4 neutropenia ( 94 % versus 84 % , difference = 11 % , 95 % CI = 7 % to 14 % ; P<.001 ) and neutropenic complications than treatment with paclitaxel-carboplatin , although myelosuppression did not influence dose delivery or patient safety . Global quality of life was similar in both arms , but substantive differences in many symptom scores favored docetaxel . CONCLUSIONS Docetaxel-carboplatin appears to be similar to paclitaxel-carboplatin in terms of progression-free survival and response , although longer follow-up is required for a definitive statement on survival . Thus , docetaxel-carboplatin represents an alternative first-line chemotherapy regimen for patients with newly diagnosed ovarian cancer BACKGROUND The combination of carboplatin and paclitaxel is the st and ard of care for the treatment of ovarian cancer , yet rates of recurrence and death remain high . We performed a prospect i ve r and omized phase III study to examine whether sequential administration of topotecan can improve the efficacy of carboplatin and paclitaxel in first-line treatment of advanced epithelial ovarian cancer . METHODS A total of 1308 patients with previously untreated ovarian cancer ( International Federation of Gynecology and Obstetrics stages IIB-IV ) were r and omly assigned to receive six cycles of paclitaxel and carboplatin followed by either four cycles of topotecan ( TC-Top ; 658 patients ) or surveillance ( TC ; 650 patients ) on a 3-week per cycle schedule . The primary endpoint was overall survival , and secondary endpoints were progression-free survival , response rate , toxicity , and quality of life . Time-to-event data were analyzed using the Kaplan-Meier method , and a stratified log-rank test was used to compare distributions between treatment groups . Hazard ratios ( HRs ) with 95 % confidence intervals ( CIs ) were estimated using a Cox proportional hazards model . Categorical data were compared using a stratified Cochran-Mantel-Haenszel test . All statistical tests were two-sided . RESULTS Median progression-free survival was 18.2 months in the TC-Top arm versus 18.5 months in the TC arm ( stratum-adjusted HR = 0.97 [ 95 % CI = 0.85 to 1.10 ] ; P = .688 ) . Median overall survival was 43.1 months for the TC-Top arm versus 44.5 months for the TC arm ( stratum-adjusted HR = 1.01 [ 95 % CI = 0.86 to 1.18 ] ; P = .885 ) . At 3 years , overall survival in both arms was 57 % ( 58.5 % in the TC arm and 55.7 % in the TC-Top arm ) . Compared with patients in the TC arm , patients in the TC-Top arm had more grade 3 - 4 hematologic toxic effects ( requiring more supportive care ) and more grade 3 - 4 infections ( 5.1 % versus 2.7 % ; P = .034 ) but did not have a statistically significant increase in febrile neutropenia ( 3.3 % versus 3.1 % ; P = .80 ) . Among patients who had measurable disease ( TC , n = 147 ; TC-Top , n = 145 ) , overall ( i.e. , complete or partial ) response was 69.0 % ( 95 % CI = 61.4 % to 76.5 % ) in the TC-Top arm and 76.2 % ( 95 % CI = 69.3 % to 83.1 % ) in the TC arm ( P = .166 ) . CONCLUSIONS The sequential addition of topotecan to carboplatin-paclitaxel did not result in superior overall response or progression-free or overall survival . Therefore , this regimen is not recommended as st and ard of care treatment for ovarian cancer OBJECTIVE Effective therapies with a low rate of side effects are warranted in the 2nd-line setting in ovarian cancer . Both topotecan and the alkylating agent treosulfan have demonstrated efficacy in this patient group and are broadly used in Germany . Therefore , we started a prospect ively r and omized phase III trial comparing these two drugs in early recurrent ovarian cancer . METHODS Patients having relapsed after platinum-taxane therapy were r and omized to receive either topotecan or treosulfan . Stratification depended on platinum sensitivity ( stratum 1 : up to 6 months after primary chemotherapy , stratum 2 : 6 to 12 months ) . RESULTS A total of 274 patients were treated either with topotecan ( 136 patients ) or treosulfan ( 138 ) . Hematologic toxicity was significantly more frequent with topotecan but without severe clinical consequences . Non hematologic toxicity was similar in both study arms . Overall survival was significantly longer with topotecan ( p=0.0023 ) , with a median of 55.0 weeks versus 41.0 weeks as well as progression-free survival ( p=0.0020 ) with a median of 23.1 weeks versus 12.7 weeks . Similar results were found for stratum 2 subgroup . Overall response rate was 27.5 % for topotecan and 16.0 % for treosulfan ( p=0.0307 ) . In stratum 1 progression-free survival was 18.1 weeks for topotecan and 9.4 weeks for treosulfan ( p=0.0476 ) , but there was no difference in overall survival in this prognostic poor subgroup . CONCLUSIONS This r and omized phase III trial could detect superiority of topotecan versus treosulfan in patients with recurrent disease after platinum-paclitaxel combination therapy . Our experience indicates that optimization of systemic treatment could improve outcome even in this poor prognostic subgroup of patients with relapsed ovarian cancer RATIONALE Canfosfamide HCl ( CAN ) is a glutathione analogue prodrug that is activated by glutathione S-transferase P1 - 1 and induces apoptosis . CAN is synergistic in vitro with carboplatin , paclitaxel and anthracyclines . METHODS Patients with platinum-refractory or -resistant ovarian cancer ( OC ) who had progressed on second-line therapy with pegylated liposomal doxorubicin ( PLD ) or topotecan ( TOPO ) , were r and omised between CAN 1000 mg/m(2 ) IV q 3 weeks or to either PLD 50mg/m(2 ) IV q 4 weeks or TOPO 1.5mg/m(2 ) IV d1 - 5 q 3 weeks . RESULTS About 461 patients were r and omised after stratification for ECOG performance status , prior therapy , and bulky ( > 5 cm ) disease . Groups were well balanced . In the control arm 58 % and 42 % were treated with PLD and TOPO , respectively . CAN was well tolerated with the most common grade 3 - 4 toxicities of 5 % anaemia , 4 % neutropaenia ( no febrile neutropaenia ) , 4 % thrombocytopaenia , and 7 % vomiting . Progression-free survival ( PFS ) and overall survival ( OS ) were significantly higher in the control arm ( p<0.001 and p<0.01 , respectively ) . In a subgroup analysis PFS and OS tended to be higher with PLD than with TOPO . CONCLUSION CAN was well tolerated . This is the first r and omised study showing an increased OS with third-line therapy . This might have important consequences for other recurrent OC trials First-line intravenous chemotherapy ( CT ) following debulking surgery is associated with prolonged survival , in particular in patients who achieve a pathological complete remission ( pCR ) at second-look surgery but in whom a high rate of relapses still occurs . Between 1988 and 1997 , 153 patients in pCR following platinum-based intravenous CT were r and omized between four courses of intraperitoneal cisplatin ( P ) ( 90 mg/m2 every 3 weeks ) or observation . Overall survival ( OS ) was the primary endpoint , while progression-free survival ( PFS ) was a secondary endpoint . This intent-to-treat analysis includes 16 patients who were not eligible and 17 patients who had protocol violations . The two groups were well balanced in terms of age ( median = 55 years ) , performance status ( 78 % P.S. O ) , FIGO stage ( 96 % stage III ) , histology ( serous in 66 % ) , grade ( 2 or 3 in 80 % ) , and residuum before intravenous CT ( > 1 cm in 40 % ) . Intraperitoneal CT was delivered mainly through intraperitoneal catheters ( Port-a-Cath 61 % and Tenckhoff 25 % ) . Side effects of intraperitoneal cisplatin included vomiting [ ≥ grade 2 ( 82 % ) ] , rise in serum creatinine [ ≥ grade 2 ( 14 % ) ] , abdominal pain [ grade 1–2 ( 38 % ) ] , and neurotoxicity [ grade 2–3 (15%)].After a median follow-up of 8 years , 80 patients ( 52 % ) have progressed with no difference in the pattern of relapse between the two groups and 75 patients ( 49 % ) have died ; the respective hazard ratios for PFS and OS with 95 % CI are 0.89 ( 0.59–1.33 ) and 0.82 ( 0.52–1.29 ) . These results are suggestive of a treatment benefit but do not support a change in clinical practice . Other r and omized clinical trials of intraperitoneal CT are review ed and briefly discussed PURPOSE Despite the progress that has been achieved , long-term survival rates in patients with advanced ovarian cancer are still disappointing . One attempt to improve results could be the addition of non-cross-resistant drugs to platinum-paclitaxel combination regimens . Anthracyclines were among the c and i date s for incorporation as a third drug into first-line regimens . PATIENTS AND METHODS We performed a prospect ively r and omized phase III study comparing carboplatin-paclitaxel ( TC ; area under the curve 5/175 mg/m2 , respectively ) with epirubicin 60 mg/m2 added to the same combination ( TEC ) in previously untreated patients with advanced epithelial ovarian cancer . All drugs were administered intravenously on day 1 of a 3-week schedule for a planned minimum of six courses . RESULTS Between November 1997 and February 2000 , 1,282 patients were r and omly assigned to receive either TC ( 635 patients ) or TEC ( 647 patients ) , respectively . Grade 3/4 hematologic and some nonhematologic toxicities ( nausea/emesis , mucositis , and infections ) occurred significantly more frequently in the TEC arm . Accordingly , quality -of-life analysis showed inferiority of TEC versus TC . Median progression-free survival time was 18.4 months for the TEC arm and 17.9 months for the TC arm ( hazard ratio [ HR ] , 0.95 ; 95 % CI , 0.83 to 1.07 ; P = .3342 ) . Median overall survival time was 45.8 months for the TEC arm and 41.0 months for the TC arm ( HR , 0.93 ; 95 % CI , 0.81 to 1.08 ; P = .3652 ) . Similar nonsignificant differences were observed when strata were analyzed separately . CONCLUSION Addition of epirubicin to TC did not improve survival or time to treatment failure in patients with advanced epithelial ovarian cancer ; therefore , it can not be recommended for clinical use in this population OBJECTIVE Despite the improvement in progression-free and overall survival in patients with advanced ovarian cancer associated with platinum-taxane chemotherapy , strategies are needed to prevent the greater than 70 % recurrence rate . METHOD The Southwest Oncology Group ( SWOG ) initiated a phase III intergroup trial of alpha-interferon ( IFNalpha-26 , Schering-Plough , Kenilworth , NJ ) in weekly doses of 50 x 10(6 ) IU ( for 6 doses ) versus observation only in patients with no pathological evidence of residual disease at second-look surgery in 1988 . RESULTS Patient accrual was extremely slow and the trial was permanently closed in 1999 by the SWOG Data and Safety Monitoring Committee with 74 registered patients . Of these patients , 70 were evaluable for progression-free and overall survival . There was no significant difference between the two study arms in relation to median progression-free survival ( P = 0.56 ) . The median survival duration associated with intraperitoneal alpha-interferon had not been reached versus 87 months on the observation arm . In general , intraperitoneal alpha-interferon was well tolerated . There were no treatment-related deaths or grade 4 adverse events . Although no efficacy conclusions can be drawn from this prematurely closed trial , it should be noted that 57 % of the patients on the observation arm recurred and all died , whereas 63 % recurred and only 43 % died on the intraperitoneal alpha-interferon arm . CONCLUSION Although this was a negative study , there should continue to be interest in the use of biological therapy to improve survival of patients in complete remission following primary chemotherapy The role of high-dose chemotherapy ( HDCT ) in epithelial ovarian cancer ( EOC ) remains controversial . This study was initiated to compare the efficacy and tolerability of HDCT as a consolidation approach in women with chemosensitive advanced EOC ( FIGO stages IIC – IV ) . Patients who had achieved their first clinical complete remission after six cycles of conventional paclitaxel and carboplatin combination chemotherapy were r and omly assigned to receive or not high-dose melphalan . The primary objective was to compare time to disease progression ( TTP ) . A total of 80 patients were enrolled onto the trial . Patients who were r and omized to receive HDCT were initially treated with cyclophosphamide 4 g/m2 for PBPC mobilization . HDCT consisted of melphalan 200 mg/m2 . Of the 37 patients who were allocated to HDCT , 11 ( 29.7 % ) did not receive melphalan either due to patient refusal ( n=5 ) or due to failure of PBPC mobilization ( n=6 ) . In an intent-to-treat analysis , there were no significant differences between the two arms in TTP ( P=0.059 ) as well as in overall survival ( OS ) ( P=0.38 ) The management of older and unfit women with advanced ovarian cancer requires post-operative chemotherapy but many of these patients are not suitable for high-dose cisplatin-based regimes . Carboplatin has been an easier alternative and can be given in the ambulatory setting . Historical data suggests that oral alkylating agents to be just effective with similar efficacy . In this study we have compared platinum-based carboplatin to the alkylating agent treosulfan in a population unfit to receive high-dose cisplatin . The trial r and omised patients to either intravenous carboplatin or treosulfan as single agent . The trial was stopped prematurely after the interim analysis showed improved survival and response rates in the carboplatin arm . We conclude that carboplatin is a safe and effective drug in a population that is unfit for high-dose cisplatin . Treosulfan showed limited activity but may be considered along with other oral drugs in limited circumstances . With the exception of myelosuppression , toxicity was mild in both arms . Carboplatin remains the gold st and ard in this older and less fit group of patients PURPOSE To assess whether six courses of paclitaxel are effective as consolidation treatment in patients with advanced epithelial ovarian cancer who are in complete response after first-line paclitaxel/platinum-based chemotherapy . PATIENTS AND METHODS Patients with stages IIb to IV disease in clinical or pathologic complete response after six courses of paclitaxel/platinum-based chemotherapy were r and omly allocated to either observation ( ie , control ) or six courses of paclitaxel 175 mg/m(2 ) every 3 weeks ( ie , maintenance ) . RESULTS Two hundred patients were r and omly assigned from March 1999 to July 2006 . Because of the low accrual rate , an unplanned interim analysis of futility according to the Bayesian approach was performed . Grade 2 or greater motor neurotoxicity and sensory neurotoxicity were reported in 11.3 % and 28.0 % of the paclitaxel-arm patients , respectively . After a median follow-up of 43.5 months , 107 patients ( 53 % ) had experienced relapse , and 48 patients ( 24 % ) had died . Two-year progression-free survival rates were 54 % ( 95 % CI , 43 % to 64 % ) and 59 % ( 95 % CI , 49 % to 69 % ; P = not significant ) in the control and maintenance arms , respectively . Corresponding 2-year overall survival rates were 90 % ( 95 % CI , 84 % to 97 % ) and 87 % ( 95 % CI , 80 % to 94 % ; P = not significant ) , respectively . The Cox model showed that residual disease after initial surgery ( macroscopic v no macroscopic residuum ; hazard ratio [ HR ] , 1.91 ; 95%CI , 1.21 to 3.03 ) and stage ( IIIc to IV v others ; HR , 3.10 ; 95 % CI , 1.13 to 8.48 ) were independent prognostic factors for progression-free survival , whereas the treatment arm ( maintenance v control ) had no prognostic relevance . CONCLUSION A consolidation treatment with six cycles of paclitaxel does not prolong progression-free survival or overall survival in patients in complete response after first-line paclitaxel/platinum-based regimens BACKGROUND Previously , we have shown that the combination of cyclophosphamide , doxorubicin , and cisplatin ( CAP ) and single-agent carboplatin produce similar survival and progression-free survival rates in women with ovarian cancer . Subsequently , paclitaxel combined with platinum has become a widely accepted treatment for the disease . We aim ed to compare the safety and efficacy of paclitaxel plus carboplatin with a control of either CAP or carboplatin alone . METHODS Between February , 1995 , and October , 1998 , we enrolled 2074 patients from 130 centres in eight countries . Women were r and omly assigned paclitaxel plus carboplatin or control , the control ( CAP or single-agent carboplatin ) being chosen by the patient and clinician before r and omisation . The primary outcome measure was overall survival . Secondary outcomes were progression-free survival and toxicity . Analysis was by intention to treat . FINDINGS With a median follow-up of 51 months , 1265 patients had died , and survival curves showed no evidence of a difference in overall survival between paclitaxel plus carboplatin and control ( hazard ratio 0.98 , 95 % CI 0.87 - 1.10 , p=0.74 ) . The median overall survival was 36.1 months on paclitaxel plus carboplatin and 35.4 months on control ( difference 0.7 months , 95 % CI -3.6 to 4.7 ) . 1538 patients had progressive disease or died , and again , Kaplan-Meier curves showed no evidence of a difference between the groups ( hazard ratio 0.93 , 95 % CI 0.84 - 1.03 , p=0.16 ) . Median progression-free survival was 17.3 months on paclitaxel plus carboplatin and 16.1 months on control ( difference 1.2 months , 95 % CI -0.5 to 2.8 ) . Paclitaxel plus carboplatin caused more alopecia , fever , and sensory neuropathy than carboplatin alone , and more sensory neuropathy than CAP . CAP was associated with more fever than paclitaxel plus carboplatin . INTERPRETATION Single-agent carboplatin and CAP are as effective as paclitaxel plus carboplatin as first-line treatment for women requiring chemotherapy for ovarian cancer . The favourable toxicity profile of single-agent carboplatin suggests that this drug is a reasonable option as first-line chemo therapy for ovarian cancer OBJECTIVES Interferon gamma ( IFN-gamma ) is a pleiotropic cytokine with antiproliferative , immunostimulatory , and chemosensitization properties . This trial was design ed to evaluate IFN-gamma 1b plus carboplatin and paclitaxel in treatment-naive ovarian cancer ( OC ) and primary peritoneal carcinoma ( PPC ) patients . METHODS Eligible patients were r and omized to 6 cycles of carboplatin/paclitaxel every 3 weeks or the same in combination with IFN-gamma 1b ( 100 microg 3x/wk subcutaneously ) . The primary endpoint was overall survival ( OS ) time ( target hazard ratio (HR)=0.77 ) . Secondary endpoints included progression-free survival ( target HR=0.7 ) , based on blinded review of serial imaging scans , physical exams , and CA-125 levels . RESULTS 847 patients were enrolled ( OC 774 , PPC 73 ) in Europe ( n=539 ) and North/South America ( n=308 ) from January 29 , 2002 to March 31 , 2004 and stratified according to : optimal debulking ( n=271 ) versus suboptimal debulking with plans for interval debulking ( PID ) ( n=238 ) or no PID ( n=338 ) . The study stopped early following a protocol -defined second interim analysis which revealed significantly shorter OS time in patients receiving IFN-gamma 1b plus chemotherapy compared to chemotherapy alone ( 1138 days vs. not estimable , HR=1.45 , 95 % CI=1.15 - 1.83 ) . At the time of the analysis , 169 of 426 ( 39.7 % ) patients in the IFN-gamma 1b plus chemotherapy group had died compared to 128 of 421 ( 30.4 % ) in the chemotherapy alone group . Serious adverse events were more common in the IFN-gamma 1b plus chemotherapy group ( 48.5 % vs. 35.4 % ) , primarily due to a higher incidence of serious hematological toxicities ( 34.5 % vs. 22.7 % ) . CONCLUSIONS Treatment with IFN-gamma 1b in combination with carboplatin/paclitaxel does not have a role in the first-line treatment of advanced ovarian cancer PURPOSE Most patients with advanced ovarian cancer develop recurrent disease . For those patients who recur at least 6 months after initial therapy , paclitaxel platinum has shown a modest survival advantage over platinum without paclitaxel ; however , many patients develop clinical ly relevant neurotoxicity , frequently result ing in treatment discontinuation . Thus , an alternative regimen without significant neurotoxicity was evaluated by comparing gemcitabine plus carboplatin with single-agent carboplatin in platinum-sensitive recurrent ovarian cancer patients . METHODS Patients with platinum-sensitive recurrent ovarian cancer were r and omly assigned to receive either gemcitabine plus carboplatin or carboplatin alone , every 21 days . The primary objective was to compare progression-free survival ( PFS ) . RESULTS Three hundred fifty-six patients ( 178 gemcitabine plus carboplatin ; 178 carboplatin ) were r and omly assigned . Patients received a median of six cycles in both arms . With a median follow-up of 17 months , median PFS was 8.6 months ( 95 % CI , 7.9 to 9.7 months ) for gemcitabine plus carboplatin and 5.8 months ( 95 % CI , 5.2 to 7.1 months ) for carboplatin . The hazard ration ( HR ) for PFS was 0.72 ( 95 % CI , 0.58 to 0.90 ; P = .0031 ) . Response rate was 47.2 % ( 95 % CI , 39.9 % to 54.5 % ) for gemcitabine plus carboplatin and 30.9 % ( 95 % CI , 24.1 % to 37.7 % ) for carboplatin ( P = .0016 ) . The HR for overall survival was 0.96 ( 95 % CI , 0.75 to1.23 ; P = .7349 ) . While myelosuppression was significantly more common in the combination , sequelae such as febrile neutropenia or infections were uncommon . No statistically significant differences in quality of life scores between arms were noted . CONCLUSION Gemcitabine plus carboplatin significantly improves PFS and response rate without worsening quality of life for patients with platinum-sensitive recurrent ovarian cancer PURPOSE To determine if incorporation of an additional cytotoxic agent improves overall survival ( OS ) and progression-free survival ( PFS ) for women with advanced-stage epithelial ovarian carcinoma ( EOC ) and primary peritoneal carcinoma who receive carboplatin and paclitaxel . PATIENTS AND METHODS Women with stages III to IV disease were stratified by coordinating center , maximal diameter of residual tumor , and intent for interval cytoreduction and were then r and omly assigned among five arms that incorporated gemcitabine , methoxypolyethylene glycosylated liposomal doxorubicin , or topotecan compared with carboplatin and paclitaxel . The primary end point was OS and was determined by pairwise comparison to the reference arm , with a 90 % chance of detecting a true hazard ratio of 1.33 that limited type I error to 5 % ( two-tail ) for the four comparisons . RESULTS Accrual exceeded 1,200 patients per year . An event-triggered interim analysis occurred after 272 events on the reference arm , and the study closed with 4,312 women enrolled . Arms were well balanced for demographic and prognostic factors , and 79 % of patients completed eight cycles of therapy . There were no improvements in either PFS or OS associated with any experimental regimen . Survival analyses of groups defined by size of residual disease also failed to show experimental benefit in any subgroup . CONCLUSION Compared with st and ard paclitaxel and carboplatin , addition of a third cytotoxic agent provided no benefit in PFS or OS after optimal or suboptimal cytoreduction . Dual-stage , multiarm , phase III trials can efficiently evaluate multiple experimental regimens against a single reference arm . The development of new interventions beyond surgery and conventional platinum-based chemotherapy is required to additionally improve outcomes for women with advanced EOC |
12,112 | 19,411,076 | Our meta- analysis demonstrated a trend towards decreased mortality with EM after AMI . | OBJECTIVE To determine the impact of early mobilisation ( EM ) on total mortality and non-fatal re-infa rct ion after acute myocardial infa rct ion ( AMI ) . | Background —Myocardial ischemia and infa rct ion impair baroreflex sensitivity ( BRS ) , which when depressed is predictive of future cardiac events after myocardial infa rct ion ( MI ) . The main objective of this study was to determine whether exercise training improves BRS in patients with coronary artery disease . Methods and Results —Ninety-seven male patients with and without a previous MI were recruited after myocardial revascularization surgery and r and omized into trained ( TR ) or untrained ( UTR ) groups . TR patients underwent a residential exercise program at 85 % of maximum heart rate ( HRmax ) consisting of 2 daily sessions 6 times a week for 2 weeks . Eighty-six patients ( 45 TR and 41 UTR ) completed the study . BRS was assessed at baseline and at the end of the protocol by the spontaneous baroreflex method . The st and ard deviation of mean R-R interval ( RRSD ) was also assessed as a measure of heart rate variability . At baseline , there were no significant differences between TR and UTR patients in any variable . In TR patients , BRS increased from 3.0±0.3 to 5.3±0.7 ms/mm Hg ( P < 0.001 ) , RRSD from 18.7±1.4 to 23.6±1.6 ms ( P < 0.01 ) , and R-R interval from 792.0±15.5 to 851.3±20.5 ms ( P < 0.001 ) . No significant changes occurred in UTR patients . Increases in BRS and RRSD were significant in patients either with or without a previous MI . Conclusions —Exercise training increases BRS and heart rate variability in patients with coronary artery disease . Improved cardiac autonomic function might add to the other benefits of exercise training in secondary prevention of ischemic heart disease In a multicentre trial 742 patients in 13 hospitals in Wales were r and omly allocated on the fifth day after uncomplicated myocardial infa rct ion to be mobilised on the fifth or the tenth day . The trial shows no difference in first year mortality , nor in morbidity assessed after a median period of 13 months . Follow-up after one year suggests an unexplained lower mortality during the second and third years in the late mobilisation group Abstract The effects of early mobilization after uncomplicated myocardial infa rct ion were investigated in a strictly r and omized controlled study conducted during a period of transition in the therapeutic practice of the Cantonal Hospital in Geneva , Switzerl and . One hundred fifty-four patients under age 70 who were hospitalized for acute myocardial infa rct ion and who had no complications on day 1 or day 2 were r and omly assigned to two treatment groups . In the early mobilization group , patients were treated by a physical therapist with a progressive activity program beginning on day 2 or 3 after infa rct ion . In the control group , patients underwent the traditional hospital regimen of strict bed rest for 3 or more weeks . The mean duration of hospitalization was 21.3 days for treated patients and 32.8 days for the control group . The follow-up period ranged from 6 to 20 ( average 11.2 ) months . There were no statistically significant differences between the two groups with regard to hospital or follow-up mortality , rate of reinfa rct ion , arrhythmias , heart failure , angina pectoris or ventricular aneurysm , or results of an exercise test . There was significantly greater disability in the control than in the treated group on follow-up examination . This controlled trial , based on a rigid experimental design , provides important confirmation of the benefits of early mobilization observed in uncontrolled programs in recent years Background —The predictive value of heart rate variability ( HRV ) in chronic heart failure ( CHF ) has never been tested in a comprehensive multivariate model using short-term laboratory recordings design ed to avoid the confounding effects of respiration and behavioral factors . Methods and Results —A multivariate survival model for the identification of sudden ( presumably arrhythmic ) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF ( age 52±9 years , left ventricular ejection fraction 24±7 % , New York Heart Association class 2.3±0.7 ; the derivation sample ) . Time- and frequency-domain HRV parameters obtained from an 8′ recording of ECG at baseline and during controlled breathing ( 12 to 15 breaths/min ) were challenged against clinical and functional parameters . This model was then vali date d in 242 consecutive patients referred between 1996 and 2001 ( validation sample ) . In the derivation sample , sudden death was independently predicted by a model that included low-frequency power ( LFP ) of HRV during controlled breathing ≤13 ms2 and left ventricular end-diastolic diameter ≥77 mm ( relative risk [ RR ] 3.7 , 95 % CI 1.5 to 9.3 , and RR 2.6 , 95 % CI 1.0 to 6.3 , respectively ) . The derivation model was also a significant predictor in the validation sample ( P = 0.04 ) . In the validation sample , LFP ≤11 ms2 during controlled breathing and ≥83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death ( RR 3.0 , 95 % CI 1.2 to 7.6 , and RR 3.7 , 95 % CI 1.5 to 9.0 , respectively ) . Conclusions —Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables . These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator A total of 189 patients with uncomplicated myocardial infa rct ion were selected at r and om for early or late mobilization and discharge from hospital . Patients were admitted to the study after 48 hours in a coronary care unit if they were free of pain and showed no evidence of heart failure or significant dysrhythmia . R and omization was achieved by monthly cross-over of the three medical wards to which the patients were discharged . One group of patients was mobilized immediately and discharged home after a total of nine days in hospital , and the second group was mobilized on the ninth day and discharged on the 16th day . Out-patient assessment was carried out six weeks after admission . No significant differences were observed between the groups in terms of mortality or morbidity , as reflected by the incidence of recurrent chest pain or myocardial infa rct ion , heart failure , dysrhythmia , or venous thromboembolism detected either clinical ly or by 125I-labelled fibrinogen scanning CONTEXT Trials comparing primary percutaneous coronary intervention ( PCI ) and thrombolytic therapy for treatment of acute myocardial infa rct ion ( MI ) suggest primary PCI is the superior therapy , although they differ with respect to the durability of benefit . Because PCI is often limited to hospitals that have on-site cardiac surgery programs , most acute MI patients do not have access to this therapy . OBJECTIVE To determine whether treatment of acute MI with primary PCI is superior to thrombolytic therapy at hospitals without on-site cardiac surgery and , if so , whether superiority is durable . DESIGN The Atlantic Cardiovascular Patient Outcomes Research Team ( C-PORT ) trial , a prospect i ve , r and omized trial conducted from July 1996 through December 1999 . SETTING Eleven community hospitals in Massachusetts and Maryl and without on-site cardiac surgery or extant PCI programs . PATIENTS Four hundred fifty-one thrombolytic-eligible patients with acute MI of less than 12 hours ' duration associated with ST-segment elevation on electrocardiogram . INTERVENTIONS After a formal primary PCI development program was completed at all sites , patients were r and omly assigned to receive primary PCI ( n = 225 ) or accelerated tissue plasminogen activator ( bolus dose of 15 mg and an infusion of 0.75 mg/kg for 30 minutes followed by 0.5 mg/kg for 60 minutes ; n = 226 ) . After initiation of assigned treatment , all care was determined by treating physicians . MAIN OUTCOME MEASURES Six-month composite incidence of death , recurrent MI , and stroke ; median hospital length of stay . RESULTS The incidence of the composite end point was reduced in the primary PCI group at 6 weeks ( 10.7 % vs 17.7 % ; P = .03 ) and 6 months ( 12.4 % vs 19.9 % ; P = .03 ) after index MI . Six-month rates for individual outcomes were 6.2 % vs 7.1 % for death ( P = .72 ) , 5.3 % vs 10.6 % for recurrent MI ( P = .04 ) , and 2.2 % vs 4.0 % for stroke ( P = .28 ) for primary PCI vs thrombolytic therapy , respectively . Median length of stay was also reduced in the primary PCI group ( 4.5 vs 6.0 days ; P = .02 ) . CONCLUSIONS Compared with thrombolytic therapy , treatment of patients with primary PCI at hospitals without on-site cardiac surgery is associated with better clinical outcomes for 6 months after index MI and a shorter hospital stay BACKGROUND In patients with ST-segment elevated myocardial infa rct ion ( STEMI ) , early post-thrombolysis routine angioplasty has been discouraged because of its association with high incidence of events . The GRACIA-1 trial was design ed to reassess the benefits of an early post-thrombolysis interventional approach in the era of stents and new antiplatelet agents . METHODS 500 patients with thrombolysed STEMI ( with recombinant tissue plasminogen activator ) were r and omly assigned to angiography and intervention if indicated within 24 h of thrombolysis , or to an ischaemia-guided conservative approach . The primary endpoint was the combined rate of death , reinfa rct ion , or revascularisation at 12 months . Analysis was by intention to treat . FINDINGS Invasive treatment included stenting of the culprit artery in 80 % ( 199 of 248 ) patients , bypass surgery in six ( 2 % ) , non-culprit artery stenting in three , and no intervention in 40 ( 16 % ) . Predischarge revascularisation was needed in 51 of 252 patients in the conservative group . By comparison with patients receiving conservative treatment , by 1 year , patients in the invasive group had lower frequency of primary endpoint ( 23 [ 9 % ] vs 51 [ 21 % ] , risk ratio 0.44 [ 95 % CI 0.28 - 0.70 ] , p=0.0008 ) , and they tended to have reduced rate of death or reinfa rct ion ( 7 % vs 12 % , 0.59 [ 0.33 - 1.05 ] , p=0.07 ) . Index time in hospital was shorter in the invasive group , with no differences in major bleeding or vascular complications . At 30 days both groups had a similar incidence of cardiac events . In-hospital incidence of revascularisation induced by spontaneous recurrence of ischaemia was higher in patients in the conservative group than in those in the invasive group . INTERPRETATION In patients with STEMI , early post-thrombolysis catheterisation and appropriate intervention is safe and might be preferable to a conservative strategy since it reduces the need for unplanned in-hospital revascularisation , and improves 1-year clinical outcome To determine the effects of early ambulation on peripheral venous thrombosis in the coronary care unit , 29 patients with acute myocardial infa rct ion had daily 125I-fibrinogen point counting of both legs using a st and ard portable technique in the first 3 to 7 days after admission . Twenty-one patients underwent early ambulation during the initial 3 days , while 8 remained at complete bed rest for 5 days . Only 2 of 21 early ambulated patients had positive fibrinogen point counts , in contrast to 5 of 8 nonambulated patients ( P less than 0.01 ) . With heart failure , only 2 of 9 ambulated patients had positive point counts , compared with 4 of 5 nonambulated patients ( P less than 0.05 ) . In 16 patients undergoing venography , point counts were confirmed in 6 positive and 10 negative findings . These results show that the high frequency of peripheral venous thrombosis in immobilized acute myocardial infa rct ion patients , particularly those with heart failure , can be effectively reduced by early ambulation Early mobilisation after acute myocardial infa rct ion is said to increase the risk of ventricular aneurysm and -rupture , reinfa rct ion , sudden death , and heart failure . In order to evaluate these possible negative effects , we run a prospect i ve and controlled study : 2 X 100 consecutive patients with acute myocardial infa rct ion were mobilized conventionally ( A ) and according to an early mobilisation programme ( B ) respectively-the two groups were comparable according to age , sex , CHD-history , infa rct ion transmural/non transmural and coronary prognostic index ( Norris ) . There was a significant reduction in the average hospital stay from 31.4 days in group A to 25.8 in group B. The patients were followed up for 32 ( A ) and 46 days ( B ) respectively . In the early mobilized group we found no increased risk for heart failure , reinfa rct ion , or sudden death . On the other side , early mobilisation has many psychological , oeconomic and social advantages for patients and hospital A prospect i ve , controlled , r and omized study was done to compare the effect of early and late ambulation in hospitalized patients with acute myocardial infa rct ion . All patients surviving longer than the first five days were studied ; 64 patients were mobilized on day six and discharged on day 12 , and 65 were mobilized on day 13 and discharged on day 19 . Follow-up observation lasted from six to 52 weeks . Of patients without complications until day six , eight out of 32 in the early and 16 of 35 in the late groups manifested complications during the follow-up period ( p smaller than 0.05 ) . Of those who had complications before day six , seven of 32 and 26 of 30 still had or acquired new complications until last seen ( p small than 0.0001 ) . The number of serious complications in the two groups was eight and 24 respectively ( p smaller than 0.001 ) . We conclude that early ambulation is beneficial irrespective of complications on admission BACKGROUND In Western countries , the length of hospital stay after acute myocardial infa rct ion ( AMI ) has decreased dramatically during the past 3 decades and is now approximately 1 week . However , epidemiological data concerning the length of hospital stay , its predictors and trends based on a large-scale sample are still limited in Japan . METHODS AND RESULTS The study group comprised 4,113 surviving AMI patients who were enrolled in the Osaka Acute Coronary Insufficiency Study from April 1998 to March 2003 . The mean length of hospital stay was 31.2 days . Clinical factors ( patient characteristics , severity of infa rct ion , therapy , and in-hospital complications ) only explained 26 % of the variation in hospital stay . The mean hospital stay was significantly longer in 1998 than in 2002 . In 2002 , occupational status and admission to a high-volume hospital were independent predictors of a shorter hospital stay , but this association was not observed in 1998 . CONCLUSIONS The hospital stay is still extremely long in Japan and clinical factors do not provide an explanation . The findings of the present study suggest that the hospital stay could be reduced in some patients with AMI , but r and omized studies are needed to examine the feasibility of early discharge Prolonged bed rest after myocardial infa rct ion is thought to result in deconditioning , manifested by increased heart-rate and blood-pressure responses to exercise and decreased functional capacity . We studied the effects of early , supervised exercises in preventing deconditioning after acute myocardial infa rct ion . Eighty-four patients were r and omized to a control group and 174 to an exercise group . Enrollment in the exercise program occurred an average of 4.5 days after admission ( range , one to nine ) . Discharge from the hospital occurred an average of 10.3 days after admission in the control group and 10.4 days in the exercise group . Most patients had a low-level treadmill test on the day before hospital discharge . There were no differences between the two groups in the clinical , hemodynamic , or electrocardiographic responses to the treadmill test . Incidences of complications and deaths ( one death in each group ) during hospitalization were not significantly different in the two groups , although six patients ( 3 per cent , all in the exercise group ) required cardiac surgery -- four because of recurrent chest pain and two because of rupture of heart muscle . Thus , we were unable to demonstrate any significant beneficial or deleterious effects of an early , in-hospital exercise program Signs of sympathetic hyperactivity and low parasympathetic activity have been found during the acute and recovery phases of myocardial infa rct ion and have been associated with an increased risk of cardiac mortality . Beneficial effects of physical training have been recently reported in post-myocardial infa rct ion patients . We tested the hypothesis that physical training would be effective in improving the autonomic balance by study ing 22 patients with a first and recent myocardial infa rct ion who were r and omly assigned to enter or not enter a 4-week in-hospital physical training program . Spectral indices of heart rate variability were analyzed at rest and during 70 degrees head-up tilt before and after the index training , not training period . As expected , physical training induced a significant increase in exercise duration ( 13.7 + /- 0.8 vs 17.1 + /- 0.1 min , p less than 0.001 ) and in the anaerobic threshold ( 9.5 + /- 0.7 vs 12.0 + /- 1.0 min , p less than 0.02 ) in trained patients , while no changes were observed in the untrained group . At entry , in both groups , spectral profile of heart rate variability was characterized by a predominant LF component and a smaller HF component with no further modification after head-up tilt . After 4 weeks , in resting conditions , no significant changes in spectral components were observed in both trained and untrained patients . After physical training , head-up tilt produced significant modifications in spectral profile with an increase in the LF component ( 84 + /- 3 vs 69 + /- 5 nu , p less than 0.01 ) and a decrease in the HF component ( 7 + /- 1 vs 19 + /- 4 nu , p less than 0.05 ) in trained patients , while no changes were observed in the untrained patients . Our data suggest that in postmyocardial infa rct ion patients , 4 weeks of physical training may induce an improvement in the autonomic balance with a restoration toward normal in the reflex activity of the system Type 2 diabetes is a strong risk factor for coronary heart disease and sudden cardiac death . It is associated with reduced baroreflex sensitivity ( BRS ) and heart rate variability ( HRV ) , which are indicators of increased risk for mortality and morbidity in various patient population s. This study was design ed to assess the effects of exercise training on BRS , HRV , and hemodynamics in patients with type 2 diabetes . Subjects ( 50 men , mean age 53.3 + /- 5.1 years ) with type 2 diabetes were r and omized into either a control group , in which they received conventional treatment only , or an exercise group , in which they received conventional treatment together with heart rate-controlled endurance training twice a week and supervised muscle strength training twice a week for 12 months . Measurements taken at baseline and follow-up included VO(2max ) , st and ard time and frequency domain measures of HRV during 24-h recording , and BRS by the phenylephrine method . Cardiac index , systemic vascular resistance index , stroke index , and pulse wave velocity were measured by whole-body impedance cardiography . Significant improvements in VO(2max ) ( exercise group : + 2.3 ml x kg(-1 ) x min(-1 ) ; P < 0.005 vs. control group ) , muscle strength , and glycemic control ( exercise group : HbA(1c ) -0.9 % ; P < 0.001 vs. control group ) were observed in the exercise group . BRS increased in the exercise group , from 6.8 to 8.6 ms/mmHg , and decreased in the control group , from 7.5 to 6.4 ms/mmHg ( 95 % CI for the difference between 0.05 and 4.36 ms/mmHg ; P < 0.05 ) . No significant changes in the time or frequency domain measures of HRV or in systemic hemodynamics were observed . We concluded that exercise training improves BRS sensitivity in type 2 diabetes subjects in addition to increasing the exercise capacity and muscle strength and improving glucose control . These beneficial effects in reflectory autonomic regulation and glucose control caused by exercise may be associated with improved prognosis of type 2 diabetes patients R and omized clinical trials of cardiac rehabilitation following myocardial infa rct ion have typically demonstrated a lower mortality in treated patients , but with a statistically significant reduction in only one trial . To overcome the problem of not being able to detect small but clinical ly important benefits in mortality in r and omized clinical trials of exercise and risk factor rehabilitation after myocardial infa rct ion with small numbers of patients , we carried out a meta- analysis on the combined results of ten r and omized clinical trials that included 4347 patients ( control , 2145 patients ; rehabilitation , 2202 patients ) . The pooled odds ratios of 0.76 ( 95 % confidence intervals , 0.63 to 0.92 ) for all-cause death and of 0.75 ( 95 % confidence intervals , 0.62 to 0.93 ) for cardiovascular death were significantly lower in the rehabilitation group than in the control group , with no significant difference for nonfatal recurrent myocardial infa rct ion . These results suggest that , for appropriately selected patients , comprehensive cardiac rehabilitation has a beneficial effect on mortality but not on nonfatal recurrent myocardial infa rct ion Abstract In this trial of early mobilisation and discharge patients with uncomplicated myocardial infa rct ion were all given 7 days of bed rest , followed by mobilisation on day 8 and discharge on day 15 ( 95 patients , group E ) or mobilisation on day 21 and discharge on day 28 ( 104 patients , group L ) . On admission patients in the two groups were well matched . Patients were encouraged to return to work 1 month after discharge . Follow-up was done via outpatient clinics , and the results were analysed at 8 months after discharge . Group E fared no worse than group L in respect of mortality , complication-rates , ventricular aneurysm ( on X-ray ) , or return to work Despite the current practice of early mobilization and early hospital discharge after uncomplicated acute myocardial infa rct ion ( AMI ) , physicians are reluctant to permit normal physical and social activity for several weeks after the AMI " to allow the heart to heal . " This study tested whether it was possible to identify a low risk group of patients on day 3 after AMI , and whether vigorous early mobilization from days 4 through 7 affected left ventricular function and volumes ( studied by gated blood pool scan on days 4 and 14 ) . There was 1 death in 3 months in 45 patients with uncomplicated AMI suitable for r and omization to activity ( group A ) compared with 11 deaths in 55 patients unsuitable for rapid early mobilization ( group B ) ( p less than 0.01 ) . Early vigorous mobilization in 24 of the group A patients compared with sedentary care in 20 did not affect change in ejection fraction , end-diastolic volume , end systolic-volume , stroke volume , heart rate or cardiac output between days 4 and 14 . A very low risk group suitable for early vigorous mobilization can be defined on day 3 after AMI ; further , vigorous early mobilization does not affect left ventricular function or volumes . Early return to physical , social and occupational activity after uncomplicated AMI should result in marked reduction in direct and indirect costs of AMI |
12,113 | 28,156,805 | Conclusions The findings suggest that CE models can lead to improved health and health behaviours among disadvantaged population s if design ed properly and implemented through effective community consultation and participation . | Background Although community engagement ( CE ) is widely used in health promotion , components of CE models associated with improved health are poorly understood . | Underserved minority population s in the US Affiliated Pacific Isl and s ( USAPI ) , Hawaii , and Alaska display disproportionate rates of childhood obesity . The region ’s unique circumstance should be taken into account when design ing obesity prevention interventions . The purpose of this paper is to ( a ) , describe the community engagement process ( CEP ) used by the Children ’s Healthy Living ( CHL ) Program for remote underserved minority population s in the USAPI , Hawaii , and Alaska ( b ) report community-identified priorities for an environmental intervention addressing early childhood ( ages 2–8 years ) obesity , and ( c ) share lessons learned in the CEP . Four communities in each of five CHL jurisdictions ( Alaska , American Samoa , Commonwealth of the Northern Mariana Isl and s , Guam , Hawai‘i ) were selected to participate in the community-r and omized matched-pair trial . Over 900 community members including parents , teachers , and community leaders participated in the CEP over a 14 month period . The CEP was used to identify environmental intervention priorities to address six behavioral outcomes : increasing fruit/vegetable consumption , water intake , physical activity and sleep ; and decreasing screen time and intake of sugar sweetened beverages . Community members were engaged through Local Advisory Committees , key informant interviews and participatory community meetings . Community-identified priorities centered on policy development ; role modeling ; enhancing access to healthy food , clean water , and physical activity venues ; and healthy living education . Through the CEP , CHL identified culturally appropriate priorities for intervention that were also consistent with the literature on effective obesity prevention practice s. Results of the CEP will guide the CHL intervention design and implementation . The CHL CEP may serve as a model for other underserved minority isl and population Background We report the main results , among adults , of a cluster-r and omised-trial of Well London , a community-engagement programme promoting healthy eating , physical activity and mental well-being in deprived neighbourhoods . The hypothesis was that benefits would be neighbourhood-wide , and not restricted to intervention participants . The trial was part of a multicomponent process/ outcome evaluation which included non-experimental components ( self-reported behaviour change amongst participants , case studies and evaluations of individual projects ) which suggested health , well-being and social benefits to participants . Methods Twenty matched pairs of neighbourhoods in London were r and omised to intervention/control condition . Primary outcomes ( five portions fruit/vegetables/day ; 5 × 30 m of moderate intensity physical activity/week , abnormal General Health Question naire (GHQ)-12 score and Warwick – Edinburgh Mental Well-being Scale ( WEMWBS ) score ) were measured by postintervention question naire survey , among 3986 adults in a r and om sample of households across neighbourhoods . Results There was no evidence of impact on primary outcomes : healthy eating ( relative risk [ RR ] 1.04 , 95 % CI 0.93 to 1.17 ) ; physical activity ( RR:1.01 , 95 % CI 0.88 to 1.16 ) ; abnormal GHQ12 ( RR:1.15 , 95 % CI 0.84 to 1.61 ) ; WEMWBS ( mean difference [ MD ] : −1.52 , 95 % CI −3.93 to 0.88 ) . There was evidence of impact on some secondary outcomes : reducing unhealthy eating-score ( MD : −0.14 , 95 % CI −0.02 to 0.27 ) and increased perception that people in the neighbourhood pulled together ( RR : 1.92 , 95 % CI 1.12 to 3.29 ) . Conclusions The trial findings do not provide evidence supporting the conclusion of non-experimental components of the evaluation that intervention improved health behaviours , well-being and social outcomes . Low participation rates and population churn likely compromised any impact of the intervention . Imprecise estimation of outcomes and sampling bias may also have influenced findings . There is a need for greater investment in refining such programmes before implementation ; new methods to underst and , longitudinally different pathways residents take through such interventions and their outcomes , and new theories of change that apply to each pathway Objective : To evaluate the effectiveness of a lay delivered intervention to reduce Latino children ’s exposure to environmental tobacco smoke ( ETS ) . The a priori hypothesis was that children living in households that were in the intervention group would have lower exposure over time than measurement only controls . Design : A two group , r and omised control trial was conducted . Setting : Areas of San Diego county with a large Latino population . Participants : 143 Latino parent – child pairs . Intervention : Trained bicultural and bilingual Latina lay community health advisors , or promotoras , conducted problem solving aim ed at lowering the target child ’s exposure to ETS in the household . Six home and telephone sessions were delivered by the promotoras over a four month period . Main outcome measures : Outcome measures were collected at baseline , immediately post-intervention , three months post-intervention , and 12 months post-intervention . Four outcomes were considered : ( 1 ) parent ’s paper- and -pencil reports of the child ’s past month exposure ; ( 2 ) hair sample s from the child analysed for past month nicotine ; ( 3 ) hair sample s from the child analysed for past month cotinine ; and ( 4 ) per cent confirmed reducers . Results : There were no significant condition-by-time interactions , the term indicative of a differential intervention effect . Significant or near significant time main effects were seen for children ’s hair cotinine , per cent confirmed reducers , and , in particular , parent reports of exposure . Conclusions : Applying a lay promotora model to deliver the behavioural problem solving intervention unfortunately was not effective . A likely explanation relates to the difficulty of delivering a relatively complex intervention by lay women untrained in behaviour change theory and research methods Background Cardiovascular disease remains the leading killer of women in most developed areas of the world . Rates of physical inactivity and poor nutrition , which are two of the most important modifiable risk factors for cardiovascular disease in women , are substantial . This study sought to examine the effectiveness of a community-based lifestyle-modification program on increasing women 's physical activity in a r and omized trial guided by community-based participatory research ( CBPR ) methods . Methods A total of 335 healthy , 25–64 years old women who had been selected by a multiple-stage stratified cluster r and om sampling method in Bushehr Port/I.R. Iran , were r and omized into control and intervention groups . The intervention group completed an 8-week lifestyle modification program for increasing their physical activity , based on a revised form of Choose to Move program ; an American Heart Association Physical Activity Program for Women . Audio-taped activity instructions with music and practical usage of the educational package were given to the intervention group in weekly home-visits by 53 volunteers from local non-governmental and community-based organizations . Results Among the participants , the percentage who reported being active ( at lease 30 minutes of moderate intensity physical activity for at least 5 days a week , or at least 20 minutes of vigorous physical activity for at least three days a week ) increased from 3 % and 2.7 % at baseline to 13.4 % and 3 % ( p < 0.0001 ) at the ending of the program in the intervention and control groups , respectively . The participants in the intervention group reported more minutes of physical activity per week ( mean = 139.81 , SE = 23.35 ) than women in the control group ( mean = 40.14 , SE = 12.65 ) at week 8 ( p < 0.0001 ) . The intervention group subjects exhibited a significantly greater decrease in systolic blood pressure ( -10.0 mmHg ) than the control group women ( + 2.0 . mmHg ) . The mean ranks for posttest healthy heart knowledge in the intervention and control groups were 198.91 and 135.77 , respectively ( P < 0.0001 ) . Conclusion An intervention based on CBPR methods can be effective for the short-term adoption of physical activity behavior among women . The development of participatory process to support the adequate delivery of lifestyle-modification programs is feasible and an effective healthcare delivery strategy for cardiovascular community health promotion . Trial Registration This study tested the effects of an exercise and diet modification training program for weight loss among Latinas . Forty four obese women were assigned to an experimental training group ( n = 22 ) or a control ( n = 22 ) , at r and om . One session per week for eight weeks included instruction for diet modification and walking for exercise , and all women were led in 20 min of walking during each session . Instruction was provided by a bi-cultural Spanish-speaking physician . Statistically significant ( P < 0.05 ) decreases , relative to controls , were obtained for Body Mass Index , waist to hip ratio , and serum cholesterol . Significant increases were obtained for fitness , exercise rate and frequency , and diet/exercise knowledge . Results suggest that the training was effective for decreasing obesity and increasing fitness among Low SES , Mexican-American women . Implication s for weight control and disease prevention among under-served population s are discussed Introduction The high prevalence of cardiovascular disease ( CVD ) in the Hispanic population of the United States , together with low rates of health insurance coverage , suggest a potential cardiovascular health crisis . The objective of Project HEART ( Health Education Awareness Research Team ) was to promote behavior changes to decrease CVD risk factors in a high-risk Hispanic border population . Methods Project HEART took place from 2005 through 2008 as a r and omized community trial with a community-based participatory research framework using promotores de salud ( community health workers ) . A total of 328 participants with at least 1 CVD risk factor were selected by r and omizing 10 US Census tracts in El Paso , Texas , to either the experimental or the control group . The experimental group ( n = 192 ) was assigned to a series of 8 health classes using the Su Corazón , Su Vida curriculum . After 2 months of educational sessions , the group was followed for 2 months . The control group ( n = 136 ) was given basic educational material s at baseline , and no other intervention was used . Main outcomes of interest included changes in health behaviors and clinical measures . Results Participants in the experimental group showed more awareness of CVD risk factors , more confidence in the control of these factors , and improved dietary habits ( ie , lower salt and cholesterol intake , better weight-control practice s ) compared with the control group . Total cholesterol was 3 % lower in the experimental than in the control participants , and non – high-density lipoprotein cholesterol and low-density lipoprotein cholesterol were both 5 % lower . Conclusion The HEART trial suggests that community health education using promotores de salud is a viable strategy for CVD risk reduction in a Hispanic border community BACKGROUND Community mobilisation through participatory women 's groups might improve birth outcomes in poor rural communities . We therefore assessed this approach in a largely tribal and rural population in three districts in eastern India . METHODS From 36 clusters in Jharkh and and Orissa , with an estimated population of 228 186 , we assigned 18 clusters to intervention or control using stratified r and omisation . Women were eligible to participate if they were aged 15 - 49 years , residing in the project area , and had given birth during the study . In intervention clusters , a facilitator convened 13 groups every month to support participatory action and learning for women , and facilitated the development and implementation of strategies to address maternal and newborn health problems . The primary outcomes were reductions in neonatal mortality rate ( NMR ) and maternal depression scores . Analysis was by intention to treat . This trial is registered as an International St and ard R and omised Controlled Trial , number IS RCT N21817853 . FINDINGS After baseline surveillance of 4692 births , we monitored outcomes for 19 030 births during 3 years ( 2005 - 08 ) . NMRs per 1000 were 55.6 , 37.1 , and 36.3 during the first , second , and third years , respectively , in intervention clusters , and 53.4 , 59.6 , and 64.3 , respectively , in control clusters . NMR was 32 % lower in intervention clusters adjusted for clustering , stratification , and baseline differences ( odds ratio 0.68 , 95 % CI 0.59 - 0.78 ) during the 3 years , and 45 % lower in years 2 and 3 ( 0.55 , 0.46 - 0.66 ) . Although we did not note a significant effect on maternal depression overall , reduction in moderate depression was 57 % in year 3 ( 0.43 , 0.23 - 0.80 ) . INTERPRETATION This intervention could be used with or as a potential alternative to health-worker-led interventions , and presents new opportunities for policy makers to improve maternal and newborn health outcomes in poor population s. FUNDING Health Foundation , UK Department for International Development , Wellcome Trust , and the Big Lottery Fund ( UK ) ABSTRACT BACKGROUND Depression contributes to disability and there are ethnic/racial disparities in access and outcomes of care . Quality improvement ( QI ) programs for depression in primary care improve outcomes relative to usual care , but health , social and other community-based service sectors also support clients in under-re source d communities . Little is known about effects on client outcomes of strategies to implement depression QI across diverse sectors . OBJECTIVE To compare the effectiveness of Community Engagement and Planning ( CEP ) and Re sources for Services ( RS ) to implement depression QI on clients ’ mental health-related quality of life ( HRQL ) and services use . DESIGN Matched programs from health , social and other service sectors were r and omized to community engagement and planning ( promoting inter-agency collaboration ) or re sources for services ( individual program technical assistance plus outreach ) to implement depression QI toolkits in Hollywood-Metro and South Los Angeles . PARTICIPANTS From 93 r and omized programs , 4,440 clients were screened and of 1,322 depressed by the 8-item Patient Health Question naire ( PHQ-8 ) and providing contact information , 1,246 enrolled and 1,018 in 90 programs completed baseline or 6-month follow-up . MEASURES Self-reported mental HRQL and probable depression ( primary ) , physical activity , employment , homelessness risk factors ( secondary ) and services use . RESULTS CEP was more effective than RS at improving mental HRQL , increasing physical activity and reducing homelessness risk factors , rate of behavioral health hospitalization and medication visits among specialty care users ( i.e. psychiatrists , mental health providers ) while increasing depression visits among users of primary care/public health for depression and users of faith-based and park programs ( each p < 0.05 ) . Employment , use of antidepressants , and total contacts were not significantly affected ( each p > 0.05 ) . CONCLUSION Community engagement to build a collaborative approach to implementing depression QI across diverse programs was more effective than re sources for services for individual programs in improving mental HRQL , physical activity and homelessness risk factors , and shifted utilization away from hospitalizations and specialty medication visits toward primary care and other sectors , offering an exp and ed health-home model to address multiple disparities for depressed safety-net clients We investigated whether barriers to onsite parental involvement in the Bienestar Health Program Parent Component could be identified and whether participation rates could be increased by addressing these barriers . All nonparticipating parents of fourth- grade students of San Antonio Independent School District from 4 schools , which were selected r and omly from 20 intervention schools in Bienestar , were invited to take part in this study . A total of 47 of 223 ( 21 % ) parents engaged in one of four focus groups offered . Parents identified barriers to their involvement in Bienestar that fit into five descriptive categories : ( a ) low value , ( b ) high cost , ( c ) competing family dem and s , ( d ) concerns about the program design , and ( e ) social role norms . The Bienestar Parent Component was then modified according to the focus group findings , which result ed in a marked increase in parental involvement from 17 % to 37 % overall . These findings suggest that even when parents are involved in the initial design of parent-friendly and culturally sensitive programs , as was the case for Bienestar , maximizing parental involvement may require additional assessment , identification , and remediation of barriers INTRODUCTION This article describes the development of a community-based participatory research ( CBPR ) process conducted in the context of a r and omized community health education trial utilizing community health workers ( CHWs ) . OBJECTIVES To present lessons learned from the utilization of CBPR methodology in a cardiovascular disease ( CVD ) prevention trial among Mexican American adults in a U.S.-Mexico border community and to disseminate the baseline results associated with risk factors for CVD and their associated demographic and psychosocial characteristics . METHODS Participants were 328 Hispanic adults ages 30 - 75 with at least one risk factor for CVD ( overweight , smoking , high cholesterol , diabetic or hypertensive ) , who were recruited through approaching households in r and omly selected census tracts within a specified zip code area . RESULTS CBPR methods were applied during the different stages of the research enterprise to support the development and implementation of the intervention trial aim at reducing cardiovascular risk factors for Mexican American adults . Data from baseline were used as an important component of dialogue with the community . DISCUSSION CBPR proved to be a good learning process for all partners involved . The risk profile of the participants demonstrated the " epidemic " nature of CVD morbidity conditions associated with Mexican origin population s living in a U.S.-Mexico border community . The CBPR dialogue was instrumental as a process to help disseminate to the community the need for projects like the one described in this article This article describes the evaluation of a community-based participatory research ( CBPR ) community health worker ( CHW ) intervention to improve children 's asthma-related health by reducing household environmental triggers for asthma . After r and omization to an intervention or control group , 298 households in Detroit , Michigan , with a child , aged 7 to 11 , with persistent asthma symptoms participated . The intervention was effective in increasing some of the measures of lung function ( daily nadir Forced Expiratory Volume at one second [ p = .03 ] and daily nadir Peak Flow [ p = .02 ] ) , reducing the frequency of two symptoms ( “ cough that wo n't go away , ” “ coughing with exercise ” ) , reducing the proportion of children requiring unscheduled medical visits and reporting inadequate use of asthma controller medication , reducing caregiver report of depressive symptoms , reducing concentrations of dog allergen in the dust , and increasing some behaviors related to reducing indoor environmental triggers . The results suggest a CHW environmental intervention can improve children 's asthma-related health , although the pathway for improvement is complex BACKGROUND Physical inactivity is an important health risk factor that could be addressed at the community level . PURPOSE The goal of the study was to determine whether using a community-based participatory approach with park directors and park advisory boards ( PABs ) could increase physical activity in local parks . Whether involving PABs would be more effective than working with park directors alone was also tested . DESIGN An RCT intervention from October 2007 to April 2012 was used , with partial blinding of observers to the condition . All data were analyzed in 2012 . SETTING / PARTICIPANTS Of 183 eligible parks in the City of Los Angeles , 50 neighborhood park/recreation centers serving diverse population s participated . Parks were r and omized to three study arms : ( 1 ) park-director intervention ( PD-only ) ; ( 2 ) PAB intervention ( PAB/PD ) ; and ( 3 ) a control arm . Physical activity in each park was systematic ally observed , and park users and residents living within 1 mile of the park were interviewed . INTERVENTION(S ) The intervention included assessing park use , obtaining feedback from park users and community residents , training on outreach and marketing , and giving each intervention park $ 4000 to increase park-based physical activity . The PAB/PD arm required participation and concurrence on all purchases by the PAB . MAIN OUTCOME MEASURE(S ) Change in the number of park users and change in the level of park-based physical activity , expressed as MET-hours . RESULTS Relative to control parks where physical activity declined , in both the PD-only and PAB/PD parks , physical activity increased , generating an estimated average of 600 more visits/week/park , and 1830 more MET-hours of physical activity/week/park . Both residents and park users in the intervention arms in the intervention arms reported increased frequency of exercise . No differences were noted between the PD-only and PAB/PD study arms . CONCLUSIONS Providing park directors and PABs with training on outreach and marketing , feedback on park users , and modest funds increased the amount of physical activity observed in parks A center-based program was design ed and implemented to promote aerobic physical activity among healthy Black-American families with children in the fifth through seventh grade s. Ninety-four Black-American families were actively recruited and r and omly as signed to an experimental or control group . Families in the experimental group were encouraged to participate in a program with the following features : one education and two fitness sessions per week for 14 weeks ; educational sessions that included individual counseling , small group education , aerobic activity , and snack components ; located in a convenient building cherished by the community ; aerobic activity sessions in a fitness center outfitted and staffed according to modern characteristics ; a variety of incentives including free transportation and babysitting and reminders to promote attendance . Per cent participation was low , with about 20 % participating in the desired fitness center sessions by the end of the program . As a result of low participation , no differences were detected beween experimental and control groups on indicators of cardiovascular fitness . In postprogram interviews , conflicts with work and school events were the most commonly reported reasons for nonattendance . We concluded that because of difficulties in at tendance , center-based programs appear to have limited value as the sole modality for intervention in public health programs for promoting physical activity among healthy OBJECTIVES : The objective of this study was to evaluate a 12-session home/community-based health promotion/obesity prevention program ( Challenge ! ) on changes in BMI status , body composition , physical activity , and diet . METHODS : A total of 235 black adolescents ( aged 11–16 years ; 38 % overweight/obese ) were recruited from low-income urban communities . Baseline measures included weight , height , body composition , physical activity ( PA ) , and diet . PA was measured by 7-day play-equivalent physical activity ( ≥1800 activity counts per minute ) . Participants were r and omly assigned to health promotion/obesity prevention that is anchored in social cognitive theory and motivational interviewing and was delivered by college-aged black mentors or to control . Postintervention ( 11 months ) and delayed follow-up ( 24 months ) evaluations were conducted . Longitudinal analyses used multilevel models with r and om intercepts and generalized estimating equations , controlling for baseline age/gender . Stratified analyses examined baseline BMI category . RESULTS : Retention was 76 % over 2 years ; overweight/obese status declined 5 % among intervention adolescents and increased 11 % among control adolescents . Among overweight/obese youth , the intervention reduced total percentage of body fat and fat mass and increased fat-free mass at delayed follow-up and increased play-equivalent physical activity at postintervention but not at delayed follow-up . Intervention adolescents declined significantly more in snack/dessert consumption than control adolescents at both follow-up evaluations . CONCLUSIONS : At postintervention , there were intervention effects on diet and PA but not BMI category or body composition . At delayed follow-up , dietary changes were sustained and the intervention prevented an increase in BMI category . Body composition was improved for overweight/obese youth . Changes in body composition follow changes in diet and PA and may not be detected immediately after intervention Context Obesity is a major public health problem in North America , particularly in Aboriginal people . Objective To determine if a household-based lifestyle intervention is effective at reducing energy intake and increasing physical activity among Aboriginal families after 6 months . Design , Participants , and InterventionR and omized , open trial of 57 Aboriginal households recruited between May 2004 and April 2005 from the Six Nations Reserve in Ohsweken , Canada . Aboriginal Health Counsellors made regular home visits to assist families in setting dietary and physical activity goals . Additional interventions included provision of filtered water , a physical activity program for children , and educational events about healthy lifestyles . Results 57 households involving 174 individuals were r and omized to intervention or usual care . Intervention households decreased consumption of fats , oils and sweets compared to usual care households ( -4.9 servings per day vs. -3 servings/day , p=0.006 ) , and this was associated with a reduction in trans fatty acids ( -0.2 vs. + 0.6 grams/day , p=0.02 ) . Water consumption increased ( + 0.3 vs. -0.1 servings/day , p<0.04 ) and soda pop consumption decreased ( -0.3 vs. -0.1 servings/day , p=0.02 ) in intervention households compared to usual care . A trend toward increased knowledge about healthy dietary practice s in children , increased leisure-time activity and decreased sedentary behaviours was observed , although these differences were not statistically significant . Conclusion A household-based intervention is associated with some positive changes in dietary practice s and activity patterns . A larger and longer-term intervention which addresses both individual change and structural barriers in the community is needed . Résumé Context eL’obésité est un problème de santé publique majeur en Amérique du Nord , particulièrement chez les Autochtones . ObjectifDéterminer si une intervention de modification du mode de vie centrée sur les ménages parvient à réduire l’apport énergétique et à accroître l’activité physique dans des familles autochtones au bout de six mois . Méthode , participants et interventionEssai ouvert aléatoire auprès de 57 ménages autochtones recrutés entre mai 2004 et avril 2005 dans la réserve des Six-Nations à Ohsweken ( Ontario ) , au Canada . Des conseillers en santé autochtone ont fait des visites à domicile périodiques pour aider les familles à se fixer des objectifs de saine alimentation et d’activité physique . D’autres mesures ont aussi été instaurées : on a fourni de l’eau filtrée aux ménages , offert un programme d’activité physique aux enfants et organisé des activités de sensibilisation aux modes de vie sains . RésultatsLes 57 ménages ( 174 personnes ) ont été répartis aléatoirement en deux groupes , l’un recevant les mesures d’intervention et l’autre , les soins habituels . Les ménages recevant les mesures d’intervention ont diminué leur consommation de matières grasses , d’huile et de sucreries par rapport aux ménages recevant les soins habituels ( -4,9 portions/jour contre -3 portions/jour , p=0,006 ) , et cette diminution était associée à une baisse de la consommation d’acides gras trans ( -0,2 contre + 0,6 g/jour , p=0,02 ) . Par ailleurs , leur consommation d’eau a augmenté ( + 0,3 contre -0,1 portion/jour , p<0,04 ) , et leur consommation de boissons gazeuses a diminué ( -0,3 contre -0,1 portion/jour , p=0,02 ) . Nous avons aussi observé une amélioration des connaissances des enfants sur la saine alimentation , une augmentation de l’activité pendant les temps libres et une diminution des comportements sédentaires , mais ces changements n’étaient pas significatifs . Conclusion Une intervention centrée sur les ménages est associée à certains changements positifs dans l’alimentation et l’activité physique . Il faudrait élargir et prolonger l’initiative , en tenant compte à la fois des changements individuels et des obstacles structurels dans la communauté Despite multidisciplinary efforts to control the nation 's obesity epidemic , obesity has persisted as one of the U.S. 's top public health problems , particularly among African Americans . Innovative approaches to address obesity that are sensitive to the unique issues of African Americans are needed . Thus , a faith-based weight-loss intervention using a community-based participatory research approach was developed , implemented , and evaluated with a rural African American faith community . A two-group , quasi-experimental , delayed intervention design was used , with church as the unit of assignment ( treatment n = 2 , control n = 2 ) and individual as the unit of observation ( treatment n = 36 , control n = 37 ) . Weekly small groups led by trained community members met for 8 weeks and emphasized healthy nutrition , physical activity , and faith 's connection with health . The mean weight loss of the treatment group was 3.60 ± 0.64 lbs . compared to the 0.59 ± 0.59-lb loss of the control group BACKGROUND Neonatal mortality accounts for a high proportion of deaths in children under the age of 5 years in Bangladesh . Therefore the project for advancing the health of newborns and mothers ( Projahnmo ) implemented a community-based intervention package through government and non-government organisation infrastructures to reduce neonatal mortality . METHODS In Sylhet district , 24 clusters ( with a population of about 20 000 each ) were r and omly assigned in equal numbers to one of two intervention arms or to the comparison arm . Because of the study design , masking was not feasible . All married women of reproductive age ( 15 - 49 years ) were eligible to participate . In the home-care arm , female community health workers ( one per 4000 population ) identified pregnant women , made two antenatal home visits to promote birth and newborn-care preparedness , made postnatal home visits to assess newborns on the first , third , and seventh days of birth , and referred or treated sick neonates . In the community-care arm , birth and newborn-care preparedness and careseeking from qualified providers were promoted solely through group sessions held by female and male community mobilisers . The primary outcome was reduction in neonatal mortality . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number 00198705 . FINDINGS The number of clusters per arm was eight . The number of participants was 36059 , 40159 , and 37598 in the home-care , community-care , and comparison arms , respectively , with 14 769 , 16 325 , and 15 350 livebirths , respectively . In the last 6 months of the 30-month intervention , neonatal mortality rates were 29.2 per 1000 , 45.2 per 1000 , and 43.5 per 1000 in the home-care , community-care , and comparison arms , respectively . Neonatal mortality was reduced in the home-care arm by 34 % ( adjusted relative risk 0.66 ; 95 % CI 0.47 - 0.93 ) during the last 6 months versus that in the comparison arm . No mortality reduction was noted in the community-care arm ( 0.95 ; 0.69 - 1.31 ) . INTERPRETATION A home-care strategy to promote an integrated package of preventive and curative newborn care is effective in reducing neonatal mortality in communities with a weak health system , low health-care use , and high neonatal mortality OBJECTIVE To evaluate a culturally appropriate intervention to increase activity in overweight Mexican American women . METHODS Participants were r and omly assigned to a physical activity program or wait-list control . RESULTS Treated participants were not more active than controls at 6 or 12 months . In addition , we found no significant differences in the proportion of individuals who met an objective criterion for physical activity from baseline to 6 months in the treatment or control groups . CONCLUSION The intervention did not increase physical activity in this population . Differences in baseline activity and contamination of the control group may partially account for the outcome This report presents the process and summative evaluation results from a community-based diabetes prevention and control project implemented in response to the increasing prevalence and impact of non-insulin-dependent diabetes mellitus ( NIDDM ) in the Canadian Aboriginal population . The 24-month project targeted the registered Indian population in British Columbia 's rural Okanagan region . A participatory approach was used to plan strategies by which diabetes could be addressed in ways acceptable and meaningful to the intervention community . The strategies emphasised a combination of changing behaviours and changing environments . The project was quasi-experimental . A single intervention community was matched to two comparison communities . Workers in the intervention community conducted interviews of individuals with or at risk for diabetes during a seven-month pre-intervention phase ( n = 59 ) . Qualitative analyses were conducted to yield strategies for intervention . Implementation began in the eighth month of the project . Trend measurements of diabetes risk factors were obtained for ' high-risk ' cohorts ( persons with or at familial risk for NIDDM ) ( n = 105 ) . Cohorts were tracked over a 16-month intervention phase , with measurements at baseline , the midpoint and completion of the study . Cross-sectional population surveys of diabetes risk factors were conducted at baseline and the end of the intervention phase ( n = 295 ) . Surveys of community systems were conducted three times . The project yielded few changes in quantifiable outcomes . Activation of the intervention community was insufficient to enable individual and collective change through dissemination of quality interventions for diabetes prevention and control . Theory and previous research were not sufficiently integrated with information from pre-intervention interviews . Interacting with these limitations were the short planning and intervention phases , just 8 and 16 months , respectively . The level of penetration of the interventions mounted was too limited to be effective . Attention to process is warranted and to the feasibility of achieving effects within 24 months A r and omized controlled intervention tested the effectiveness of a community health worker ( CHW ) program in increasing compliance with annual preventive exams among uninsured Hispanic women living in a rural U.S.-Mexico border area . During 1999 - 2000 , household surveys were administered to women aged 40 and older . Uninsured women not receiving routine comprehensive preventive care were invited to participate in a free comprehensive clinical exam . Participants in the initial exam were eligible to participate in the CHW ( promotora ) intervention . Women were r and omized to one of two intervention arms . One arm received a post-card reminder for an annual preventive exam , the other a postcard reminder and follow-up visit by a promotora . Receiving the promotora intervention was associated with a 35 % increase in rescreening over the postcard-only reminder ( risk ratio [ RR ] = 1.35 , 95 % confidence interval 0.95 - 1.92 ) . Using promotoras to increase compliance with routine screening exams is an effective strategy for reaching this female population BACKGROUND The Arizona Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) project used provider counseling , health education , and community health workers ( CHWs ) to target chronic disease risk factors in uninsured , primarily Hispanic women over age 50 . METHODS Participants were recruited from two Tucson clinics participating in the National Breast and Cervical Cancer Early Detection Program ( NBCCEDP ) . Women were r and omly assigned into one of three intervention groups : ( 1 ) provider counseling , ( 2 ) provider counseling and health education , or ( 3 ) provider counseling , health education , and CHW support . At baseline and 12 months ( 1998 - 2000 ) , participants were measured for height , weight , waist and hip circumference , and blood pressure . Blood tests were conducted to check blood glucose , cholesterol , and triglyceride levels . At each time point , participants also completed 24-hour dietary recalls and question naires focusing on their physical activity levels . RESULTS A total of 217 women participated in baseline and 12-month follow-up . Three fourths were Hispanic . All three intervention groups showed an increase in self-reported weekly minutes of moderate-to-vigorous physical activity , with no significant differences between the groups . Significantly more women who received the comprehensive intervention of provider counseling , health education , and CHW support progressed to eating five fruits and vegetables per day , compared with participants who received only provider counseling or provider counseling plus health education . CONCLUSIONS All three interventions increased moderate-to-vigorous physical activity but not fruit and vegetable consumption . The intervention group with provider counseling , health education , and CHW support significantly increased the number of women meeting national recommendations for fruit and vegetable consumption OBJECTIVE To evaluate whether a community engagement and service-strengthening intervention raised awareness of family planning ( FP ) and early pregnancy bleeding ( EPB ) , and increased FP and postabortion care ( PAC ) use . METHODS The intervention was carried out in 3 communities in Kenya over 18months ; 3 additional communities served as the comparison group . A pre-post , contemporaneously controlled , quasi-experimental evaluation was conducted independently from the intervention . RESULTS Baseline characteristics were similar . Awareness of FP methods increased ( P≤0.001 ) in the intervention group . The incidence of reported EPB ( before 5months of pregnancy ) in the comparison group was 13.3 % at baseline and 6.0 % at endline ( P=0.02 ) ; 79 % at baseline and 100 % at endline sought care ( P>0.05 ) . In the intervention group , recognition and reporting of EPB increased from 9.8 % to 13.1 % ( P>0.05 ) ; 65 % sought PAC at baseline and 80 % at endline ( P=0.11 ) . The relative increase in EPB reports after the intervention was over 3 times greater in the intervention group ( P≤0.01 ) . CONCLUSION The intervention raised FP and EPB awareness but not FP and PAC services use . As fewer comparison group respondents reported experiencing EPB , the PAC impact of the intervention is unclear . Mechanisms to improve EPB reporting are needed to avoid this reporting bias BACKGROUND The Well-Integrated Screening and Evaluation for Women Across the Nation ( WISEWOMAN ) program in California ( Heart of the Family ) implements lifestyle interventions to improve health behaviors while reducing cardiovascular disease ( CVD ) risk factors among low income , uninsured , or underinsured Hispanic women aged 40 - 64 who participate in the Cancer Detection Programs : Every Woman Counts ( CDP : EWC ) . This study reports the first-year results of the California WISEWOMAN program . METHODS Heart of the Family is a within-site r and omized controlled study with an enhanced intervention group ( EIG ) and a usual care group ( UCG ) . The study was conducted between January 2006 and June 2007 at four community health centers in Los Angeles and San Diego counties . Lifestyle counseling focusing on health behaviors was provided by bilingual , bicultural ( Spanish and English ) community health workers . The study examines two outcome measures : changes in health behaviors ; and changes in the CVD risk profile , as measured by the 10-year probability of having a coronary heart disease ( CHD ) event . RESULTS Women in the EIG group ( n = 433 ) , compared to those in the UCG group ( n = 436 ) , experienced more improvements in health behaviors , both eating habits and physical activity . The improvement in the 10-year CHD risk was greater for EIG than UCG women . Multiple regression results indicate that this improvement was significantly greater when the women 's CHD risk levels were in the upper quartile at baseline . CONCLUSIONS Compared with UCG women , women in the EIG were more likely to improve their health behaviors . The CVD risk profile , as measured by the 10-year CHD risk , improved in women with the highest baseline risk |
12,114 | 23,440,131 | AND RELEVANCE Diagnostic tests for symptoms with a low risk of serious illness do little to reassure patients , decrease their anxiety , or resolve their symptoms , although the tests may reduce further primary care visits . | IMPORTANCE Diagnostic tests are often ordered by physicians in patients with a low pretest probability of disease to rule out conditions and reassure the patient .
OBJECTIVE To study the effect of diagnostic tests on worry about illness , anxiety , symptom persistence , and subsequent use of health care re sources in patients with a low pretest probability of serious illness . | Laboratory tests are purported to affect patients even if they have no diagnostic values . We tested this hypothesis by measuring clinical outcomes of 176 patients thought clinical ly to have nonspecific chest pain . They were r and omly allocated either to have a routine electrocardiogram and serum creatine phosphokinase tests ( test group ) or to have all diagnostic tests withheld ( no-test group ) . Fewer patients in the tests group ( 20 % ) reported short-term disability after the index visit than patients in the no-test group ( 46 % ) ( p = 0.001 ) . Logistic discriminant analysis confirmed that the use of diagnostic tests was an independent predictor of recovery . Patients in the test group felt that care was " better than usual " more often ( 57 % ) than patients in the no-test group ( 31 % ) ( p = 0.001 ) . After the index visit , the two groups were equally worried about serious disease and equally sparing in their use of other medial care for chest pain Objective To investigate whether providing information about normal findings before a diagnostic test improves patients ' reassurance and reduces anxiety about symptoms . Design R and omised controlled trial . Setting Outpatient cardiology clinic . Participants 92 patients with chest pain referred for a diagnostic exercise stress test . Intervention Before undergoing testing patients were r and omised to receive st and ard information ( n=28 ; control group ) , a pamphlet explaining the function of the test and the meaning of normal test results ( n=30 ; pamphlet group ) , or the pamphlet and a brief discussion about the meaning of normal test results ( n=34 ; discussion group ) . Main outcome measures The primary outcome was patients ' reported reassurance on a 5 item scale immediately after the test and at one month . Secondary outcomes were the proportion of patients still with chest pain and still taking cardiac drugs at one month . Results The mean levels of reassurance after testing and feedback from the doctor were significantly higher in the discussion group ( 42.0 , 95 % confidence interval 39.7 to 44.2 ) than in the pamphlet ( 39.2 , 36.1 to 42.3 ) and control groups ( 35.8 , 31.6 to 39.9 ) . This difference was maintained at one month . The proportion of patients still reporting chest pain at one month decreased significantly in the discussion group ( to 17 % ) and pamphlet group ( to 28 % ) but not in the control group ( to 36 % ) . A trend was for fewer patients in the discussion group to be taking cardiac drugs at one month . Conclusion Providing patients with information about normal test results before testing can improve rates of reassurance and reduce the likelihood of future reports of chest pain . Trial registration Current Controlled Trials IS RCT N87589121 Objectives : Aims were to investigate ( a ) whether neuroimaging in patients with chronic daily headache reassures patients or fails to reassure them and /or worsens outcome , impacting on service use , costs , health anxieties , and symptoms , and ( b ) whether this reassurance process occurs differentially in patients with different levels of psychological morbidity . Methods : Design : r and omised controlled trial ; setting : headache clinic in secondary care , South London ; participants : 150 patients fulfilling criteria for chronic daily headache , stratified using the Hospital Anxiety and Depression Scale ( HADS ) ; intervention : treatment as usual or the offer of an MRI brain scan ; main outcome measures : use of services , costs , and health anxiety . Results : Seventy six patients were r and omised to the offer of a brain scan and 74 patients to treatment as usual . One hundred and thirty seven ( 91 % ) primary care case notes were examined at 1 year , 103 ( 69 % ) patients completed question naires at 3 months and 96 ( 64 % ) at 1 year . Sixty six ( 44 % ) patients were HADS positive ( scored > 11 on either subscale ) . Patients offered a scan were less worried about a serious cause of the headaches at 3 months ( p = 0.004 ) , but this was not maintained at 1 year ; other health anxiety measures did not differ by scan status . However , at 1 year HADS positive patients offered a scan cost significantly less , by £ 465 ( 95 % confidence interval ( CI ) : −£1028 to −£104 ) , than such patients not offered a scan , due to lower utilisation of medical re sources . Conclusions : Neuroimaging significantly reduces costs for patients with high levels of psychiatric morbidity , possibly by changing subsequent referral patterns of the general practitioner Abstract Objective : To determine the cost effectiveness of a strategy of near patient Helicobacter pylori testing and endoscopy for managing dyspepsia . Design : R and omised controlled trial . Setting : 31 UK primary care centres . Participants : 478 patients under 50 years old presenting with dyspepsia of longer than four weeks duration . Interventions : Near patient testing for H pylori and open access endoscopy for patients with positive results . Control patients received acid suppressing drugs or specialist referral at general practitioner 's discretion . Main outcome measures : Cost effectiveness based on improvement in symptoms and use of re sources at 12 months ; quality of life . Results : 40 % of the study group tested positive for H pylori . 45 % of study patients had endoscopy compared with 25 % of controls . More peptic ulcers were diagnosed in the study group ( 7.4 % v 2.1 % , P=0.011 ) . Paired comparison of symptom scores and quality of life showed that all patients improved over time with no difference between study and control groups . No significant differences were observed in rates of prescribing , consultation , or referral . Costs were higher in the study group ( £ 367.85 v £ 253.16 per patient ) . Conclusions : The test and endoscopy strategy increases endoscopy rates over usual practice in primary care . The additional cost is not offset by benefits in symptom relief or quality of life . What is already known on this topic Patients younger than 50 without H pylori infection are unlikely to have treatable disease detected at endoscopy Such patients can be managed by acid suppression and reassurance alone Test and endoscopy ( referral of patients testing positive for H pyloriin primary care ) has been recommended as a way to reduce endoscopic workload What this paper adds Applying a test and endoscopy strategy increased the endoscopy referral rate from 25 % to 40 % The strategy produced no significant differences in symptoms or quality of life compared with usual management The increased costs of this strategy can not be Objectives To determine whether providing an information sheet to patients with acute chest pain reduces anxiety , improves health related quality of life , improves satisfaction with care , or alters subsequent symptoms or actions . Design Single centre , non-blinded , r and omised controlled trial . Setting Chest pain unit of an emergency department . Participants 700 consecutive patients with acute chest pain and no clear diagnosis at initial presentation . Interventions After a diagnostic assessment patients were r and omised to receive either st and ard verbal advice or verbal advice followed by an information sheet . Main outcome measures The primary outcome was anxiety ( hospital anxiety and depression scale ) . Secondary outcomes were depression ( hospital anxiety and depression scale ) , health related quality of life ( SF-36 ) , patient satisfaction , presentation with further chest pain within one month , lifestyle change ( smoking cessation , diet , exercise ) , further information sought from other sources , and planned healthcare seeeking behaviour in response to further pain . Results 494 of 700 ( 70.6 % ) patients responded . Compared with those receiving st and ard verbal advice those receiving advice and an information sheet had lower mean hospital anxiety and depression scale scores for anxiety ( 7.61 v 8.63 , difference 1.02 , 95 % confidence interval 0.20 to 1.84 ) and depression ( 4.14 v 5.28 , difference 1.14 , 0.41 to 1.86 ) and higher scores for mental health and perception of general health on the SF-36 . The information sheet had no significant effect on satisfaction with care , subsequent symptoms , lifestyle change , information seeking , or planned actions in the event of further pain . Conclusions Provision of an information sheet to patients with acute chest pain can reduce anxiety and depression and improve mental health and perception of general health but does not alter satisfaction with care or other outcomes . Trial registration Current Controlled Trials IS RCT N85248020 BACKGROUND Lumbar spine radiography has limited use in diagnosing the cause of acute low back pain . Consensus-based guidelines recommend that lumbar spine x-rays are not used routinely . However there have been no studies of the effect of referral for radiography at first presentation with low back pain in primary care . AIM To compare short and long-term physical , social , and psychiatric outcomes for patients with low back pain who are referred or not referred for lumbar spine x-ray at first presentation in general practice . DESIGN OF STUDY A r and omised unblinded controlled trial with an observational arm to enable comparisons to be made with patients not recruited to the trial . SETTING Ninety-four general practice s in south London and the South Thames region . METHOD Patients consulting their general practitioner ( GP ) with low back pain at first presentation were recruited to a r and omised controlled trial ( RCT ) or to an observational group . Patients in the trial were r and omly allocated to immediate referral for x-ray or to no referral . All patients were asked to complete question naires initially , and then at six weeks and one year after recruitment . RESULTS Six hundred and fifty-nine patients were recruited over 26 months : 153 to the r and omised trial and 506 to the observational arm . In the RCT referral for x-ray had no effect on physical functioning , pain or disability , but was associated with a small improvement in psychological wellbeing at six weeks and one year . These findings were supported by the observational study in which there were no differences between the groups in physical outcomes after adjusting for length of episode at presentation ; however , those referred for x-ray had lower depression scores . CONCLUSIONS Referral for lumbar spine radiography for first presentation of low back pain in primary care is not associated with improved physical functioning , pain or disability . The possibility of minor psychological improvement should be balanced against the high radiation dose involved PURPOSE To establish whether early use of magnetic resonance ( MR ) imaging or computed tomography ( CT ) influences treatment and outcome of patients with low back pain ( LBP ) and whether it is cost-effective . MATERIAL S AND METHODS In a multicenter r and omized study , two imaging policies for LBP were compared in 782 participants with symptomatic lumbar spine disorders who were referred to orthopedists or neurosurgeons . Participants were r and omly allocated to early ( 393 participants ; mean age , 43.9 years ; range , 16 - 82 years ) or delayed selective ( 389 participants ; mean age , 42.8 years ; range , 14 - 82 years ) imaging groups . Delayed selective imaging referred to imaging restricted to patients in whom a clear clinical need subsequently developed . Main outcome measures were Aberdeen Low Back Pain ( ALBP ) score , Short Form 36 ( SF-36 ) score ( for multidimensional health status ) , EuroQol ( EQ-5D ) score ( for quality -adjusted life-year [ QALY ] estimates ) , and healthcare re source use at 8 and 24 months after r and omization . Data were evaluated with analysis of covariance , ordinal logistic regression analysis , and chi(2 ) and Mann-Whitney tests . RESULTS Both groups showed improvement in ALBP score , but this was greater in the early group ( adjusted mean difference between groups , -3.05 points [ 95 % CI : -5.16 , -0.95 ; P = .005 ] and -3.62 points [ 95 % CI : -5.92 , -1.32 ; P = .002 ] at 8 and 24 months , respectively ) . Scores for SF-36 ( bodily pain domain ) and EQ-5D were also significantly better at 24 months . Clinical treatment was similar in both groups . Differences in total costs reflected cost of imaging . Imaging provided an adjusted mean additional QALY of 0.041 during 24 months at a mean incremental cost per QALY of $ 2,124 . CONCLUSION Early use of imaging does not appear to affect treatment overall . Decisions about the use of imaging depend on judgments concerning whether the small observed improvement in outcome justifies additional cost CONTEXT Somatoform disorders are an important determinant of medical care utilization , but their independent effect on utilization is difficult to determine because somatizing patients frequently have psychiatric and medical comorbidity . OBJECTIVES To assess the extent of the overlap of somatization with other psychiatric disorders ; to compare the medical utilization of somatizing and nonsomatizing patients ; and to determine the independent contribution of somatization alone to utilization . DESIGN Patients were surveyed with self-report question naires assessing somatization and psychiatric disorder . Medical care utilization was obtained from automated encounter data for the year preceding the index visit . Medical morbidity was indexed with a computerized medical record audit . SETTING Two hospital-affiliated primary care practice s. PARTICIPANTS Consecutive adults making scheduled visits to their primary care physicians on r and omly chosen days . In all , 2668 question naires were distributed , and 1914 ( 71.7 % ) were returned . Of these , 1546 ( 80.8 % ) contained complete data and met eligibility criteria . MAIN OUTCOME MEASURES Medical care utilization and costs within our hospital system in the preceding 12 months . RESULTS Two hundred ninety-nine patients ( 20.5 % ) received a provisional diagnosis of somatization ; 42.3 % of these patients had no comorbid depressive or anxiety disorder . Somatizing patients , when compared with nonsomatizing patients , had more primary care visits ( mean [ SE ] , 4.90 [ 0.32 ] vs 3.43 [ 0.11 ] ; P<.001 ) ; more specialty visits ( mean [ SE ] , 8.13 [ 0.55 ] vs 4.90 [ 0.21 ] ; P<.001 ) ; more emergency department visits ( mean [ SE ] , 1.29 [ 0.15 ] vs 0.52 [ 0.036 ] ; P<.001 ) ; more hospital admissions ( mean [ SE ] , 0.32 [ 0.051 ] vs 0.13 [ 0.014 ] ; P<.001 ) ; higher inpatient costs ( mean [ SE ] , USD 3146 [ USD 380 ] vs USD 991 [ USD 193 ] ; P<.001 ) ; and higher outpatient costs ( mean [ SE ] , USD 3208 [ USD 180 ] vs USD 1771 [ USD 91 ] ; P<.001 ) . When these results were adjusted for the presence of comorbid anxiety and depressive disorders , major medical morbidity , and sociodemographic characteristics , patients with somatoform disorder still had more primary care visits ( P = .04 ) , more specialist visits ( P = .002 ) , more emergency department visits ( P<.001 ) , more hospital admissions ( P<.001 ) , more ambulatory procedures ( P<.001 ) , higher inpatient costs ( P<.001 ) , and higher outpatient costs ( P<.001 ) . When these findings are extrapolated to the national level , an estimated USD 256 billion a year in medical care costs are attributable to the incremental effect of somatization alone . CONCLUSIONS Patients with somatization had approximately twice the outpatient and inpatient medical care utilization and twice the annual medical care costs of nonsomatizing patients . Adjusting the findings for the presence of psychiatric and medical comorbidity had relatively little effect on this association OBJECTIVES Palpitations can generate feelings of anxiety and decrease quality of life ( QoL ) due to fear of a cardiac abnormality . Continuous event recorders ( CERs ) have proven to be successful in diagnosing causes of palpitations but may affect patient QoL and anxiety . The aim is to determine anxiety and health-related (HR)-QoL and evaluate the burden of carrying a CER in general practice population s. STUDY DESIGN AND SETTING Patients ( n=244 ) participated in a r and omized trial . One group ( n=127 ) carried a CER during 4 weeks . One hundred and seventeen patients formed the usual care ( UC ) group . State-Trait Anxiety Inventory ( STAI ) and the Short Form-36 ( SF-36 ) were administered at study inclusion , after 1 , 6 months . RESULTS At baseline , patients reported greater anxiety and lower QoL than healthy population s. The CER group had three times more cardiac diagnoses than the UC group . No differences were found between CER group and UC group at 6 weeks . At 6 months , the UC group showed QoL improvement and less anxiety compared to the CER group . Type of diagnosis had influence , but did not fully explain these differences . CONCLUSION A CER does not negatively influence anxiety or QoL. Better outcomes in the UC group might be attributed to less cardiac diagnosis and more emphasis on psychological well-being BACKGROUND A policy of withholding endoscopy in Helicobacter pylori sero-negative dyspeptic patients without sinister symptoms saves up to 36 % of endoscopies . However , it is unclear whether the net cost of applying this policy outweighs that of conventional management . AIM To determine the direct ( healthcare ) and indirect ( productivity ) costs of applying a strategy of endoscopy versus no endoscopy in H. pylori sero-negative young dyspeptics in the UK . METHOD The direct and indirect incremental costs for both strategies were calculated amongst 154 H. pylori seronegative subjects r and omized to have an endoscopy or no endoscopy before subsequent management by their general practitioners . The cost per patient of each strategy was calculated using reference values in our clinical setting and sensitivity analysis was used to test different scenarios . RESULTS The total direct cost rose for the endoscopy group ( mean Pound Sterling 103 , 95 % CI 78 to 127 ) but did not change for the non-endoscopy group ( mean Pound Sterling 6 , 95 % CI -32 to 44 ) . On average , direct ( healthcare ) costs for patients in the endoscopy group rose by Pound Sterling 96 ( 95 % CI 51 to 142 ) more than those for non-endoscopy patients . Indirect ( productivity ) cost fell for the non-endoscopy group ( mean -Pound Sterling 40 , 95 % CI -220 to 140 ) compared to a rise for the endoscopy group ( mean Pound Sterling 180 , 95 % CI -60 to 420 ) ( difference not significant ) . The total cost ( including direct and indirect costs ) fell for the non-endoscopy group ( mean -Pound Sterling 34 , 95 % CI -228 to 160 ) but rose for the endoscopy group ( mean Pound Sterling 283 , 95 % CI 32 to 533)--an incremental cost of Pound Sterling 317 ( 95 % CI 0 to 634 ) . For all assumptions in the sensitivity analysis , the mean cost in the endoscopy group was at least Pound Sterling 200 higher than in the non-endoscopy group . CONCLUSIONS It is less expensive to manage H. pylori-negative dyspeptic patients aged under 45 without sinister symptoms by withholding endoscopy The aim was to evaluate the outcomes associated with four initial management strategies in new patients presenting to primary care physicians with dyspepsia . Patients with new symptoms ( no alarm features ) were r and omised to empirical therapy ( n = 11 ) , Helicobacter pylori ( HP ) serology ( n = 8) , HP breath testing ( n = 11 ) or oesophagogastroduodenoscopy ( n = 13 ) . Dyspepsia and health-related quality of life were assessed using st and ardised question naires at entry , 6 and 24 weeks post-trial enrollment . Outcomes were assessed by structured telephone interview every 6 weeks . In the initial HP testing arms , 21 % were positive ; 27 % in the oesophagogastroduodenoscopy arm had inflammatory changes without ulcers at baseline . The majority ( 67 % ) received over the counter medication after initial management . Symptom-free status was similarly common in all groups ( p = 0.49 ) ; only 20 % pursued further evaluation . Total billed charges were higher in the oesophagogastroduodenoscopy group ( US 2077 dollars ) vs. empirical therapy ( US 512 dollars ) , despite excluding the charge for initial oesophagogastroduodenoscopy , but overall , no effects on total medical charges were detected ( p = 0.10 ) . Regardless of initial management , most patients remained symptomatic , yet did not return for health care visits or undergo endoscopies . The cost of upfront endoscopy may not be the best choice for patients presenting with new dyspepsia OBJECTIVES : Whether patients with typical gastroesophageal reflux disease ( GERD ) symptoms and without alarm features should be treated empirically or undergo endoscopy first is a debated issue . In this study , our aim was to assess the efficacy , and to compare the direct costs and impact on health-related quality of life ( HRQL ) , of two treatment strategies ( empirical vs endoscopy-oriented treatment ) in a large population of patients with GERD . METHODS : In total , 612 patients were r and omized to either empirical treatment with esomeprazole 40 mg once daily ( od ) ( group 1 , N = 309 ) or endoscopy and treatment according to endoscopic findings ( group 2 , N = 303 , esomeprazole 40 mg od in patients with reflux esophagitis and esomeprazole 20 mg od in patients without esophagitis ) for 4 wk , followed by esomeprazole 20 mg od maintenance treatment in both groups . Direct costs and HRQL were analyzed in both treatment arms . RESULTS : At the end of the acute treatment phase ( week 4 ) , 267 patients in group 1 ( 86.4 % ) and 265 patients in group 2 ( 87.5 % ) were considered responders to treatment ( intention-to-treat analysis , P = 0.878 ) . Empirical treatment proved to be cost-effective by saving 38.72 euros per treated patient . At the end of the maintenance phase ( week 24 ) , a similar proportion of patients responded to treatment in the two groups ( 71.8 % vs 68.3 % , P = 0.389 ) . HRQL improved from baseline to week 24 in both groups ( difference between study groups not significant ) . CONCLUSIONS : In patients with GERD , empirical treatment with esomeprazole proved to be cost-effective compared with endoscopy-oriented treatment , and did not negatively affect patient HRQL . These results should be taken into account in the management of GERD patients in clinical practice BACKGROUND Because palpitations and light headedness often occur paroxysmally these complaints are difficult to diagnose . The hazards for a GP are too many diagnostic interventions for worried well and too few diagnostics for potentially life threatening complaints . OBJECTIVES Patient-activated memo event recorders have proved to be successful in diagnosing episodes of cardiac arrythmias in secondary care . We tested the diagnostic yield of these devices in general practice . METHODS A r and omized clinical trial in general practice . Consecutive patients with complaints of palpitations or light-headedness were r and omized to either usual care or usual care plus event-recorder . The main outcome was the difference in explained episodes . Secondary outcomes were the differences in the number and character of cardiac diagnoses and the feasibility of the event-recorder . RESULTS There were fewer patients without a diagnosis in the intervention group ( 17 % vs 38 % ; RR = 0.5 , 95 % CI 0.3 to 0.7 ) and more patients with a cardiac diagnosis ( 67 % vs. 27 % : RR 2.5 , CI 1.8 to 3,5 ) . More relevant cardiac arrhythmias were detected ( 22 % vs 7 % ) with event recording than with usual care ( RR 3.2 , 95 % CI 1.5 to 6.8 ) . CONCLUSION Patient-activated loop recorders are feasible and effective diagnostic tools in patients with palpitations or light-headedness in primary care . More research into patient characteristics and selection criteria is needed to fine-tune the use of these devices in primary care BACKGROUND Dyspepsia can be managed by initial endoscopy and treatment based on endoscopic findings , or by empirical prescribing . We aim ed to determine the cost effectiveness of initial endoscopy compared with usual management in patients with dyspepsia over age 50 years presenting to their primary care physician . METHODS 422 patients were recruited and r and omly assigned to initial endoscopy or usual management . Primary outcomes were effect of treatment on dyspepsia symptoms and cost effectiveness . Secondary outcomes were quality of life and patient satisfaction . Total costs were calculated from individual patient 's use of re sources with unit costs applied from national data . Statistical analysis of uncertainty on incremental cost-effectiveness ratio ( ICER ) was done along with a sensitivity analysis on unit costs with cost-effectiveness acceptability curves . FINDINGS In the 12 months following recruitment , 213 ( 84 % ) patients had an endoscopy compared with 75 ( 41 % ) controls . Initial endoscopy result ed in a significant improvement in symptom score ( p=0.03 ) , and quality of life pain dimension ( p=0.03 ) , and a 48 % reduction in the use of proton pump inhibitors ( p=0.005 ) . The ICER was Pound Sterling1728 ( UK Pound Sterling ) per patient symptom-free at 12 months . The ICER was very sensitive to the cost of endoscopy , and could be reduced to Pound Sterling165 if the unit cost of this procedure fell from Pound Sterling246 to Pound Sterling100 . INTERPRETATION Initial endoscopy in dyspeptic patients over age 50 might be a cost-effective intervention The recommended strategy for management of dyspepsia is empirical treatment with an H2-blocking drug , followed by endoscopy if the symptoms do not respond or recur . We compared two strategies for the management of dyspepsia -- treatment based on the results of prompt endoscopy ( group 1 ) and empirical H2-blocker treatment with diagnostic endoscopy only in cases of therapeutic failure or symptomatic relapse within 1 year ( group 2 ) . Eligible patients had symptoms severe enough to justify empirical H2-blocker therapy . Symptoms , drug consumption , and sick-leave days were assessed through monthly diaries . Patients with non-organic dyspepsia diagnosed by endoscopy did not receive ulcer drugs . Of 414 patients r and omised , 373 completed 1-year follow-up . Organic disease was found at endoscopy in 68 ( 33 % ) of 208 group-1 patients ( ulcer in 45 ) . Endoscopy was done in 136 ( 66 % ) of 206 group-2 patients . Case selection for endoscopy was not improved by the empirical treatment strategy , since the diagnostic profile was the same as in group 1 and 40 % of the expected ulcer cases remained undiagnosed . After 1 year there were no differences in symptoms or quality of life measures . The empirical treatment strategy in dyspepsia was associated with higher costs , due mainly to a higher number of sick-leave days and cost of ulcer drug use . Prompt endoscopy is a cost-effective strategy in dyspeptic patients with symptoms severe enough to justify the current practice of empirical H2-blocker treatment Background It is unclear whether endoscopy influences the management of Helicobacter pylori negative dyspepsia . Aim To determine whether endoscopy alters health-care re source utilization , quality of life and symptom outcome in H. pylori seronegative dyspeptic patients aged under 45 years ; and to determine which factors predict outcome of symptoms . Method One hundred and fifty-four H. pylori seronegative subjects were r and omized to have an endoscopy or no endoscopy before subsequent management by their GPs . Assessment was carried out at 6 months and supplementary information obtained at 12 months . Results There was no significant difference between the two groups for progression of dyspeptic symptoms ( better , same and worse ) at 6 months ( 47 % , 46 % , 7 % vs 43 % , 52 % , 5 % ) , and at 12 months ( 55 % , 34 % , 11 % vs 57 % , 28 % , 15 % ) . Prescriptions were lower in both groups at 6 and 12 months than on entry into the study , independent of endoscopy . Endoscopy did not influence quality of life , visits to GPs and days lost from work . Prognostic factors for symptom resolution at 6 months were lower severity of initial symptoms , non-smoking , non-Caucasians , less anxious patients and those not on acid suppressants . Conclusions H. pylori negative dyspeptic patients aged under 45 years without sinister symptoms could be managed without the need of an endoscopy OBJECTIVES To test the hypotheses that : ( 1 ) Lumbar spine radiography in primary care patients with low back pain is not associated with improved patient outcomes , including pain , disability , health status , sickness absence , reassurance , and patient satisfaction or belief in the value of radiography . ( 2 ) Lumbar spine radiography in primary care patients with low back pain is not associated with changes in patient management , including medication use , and the use of primary and secondary care services , physical therapies and complementary therapies . ( 3 ) Participants choosing their treatment group ( i.e. radiography or no radiography ) do not have better outcomes than those r and omised to a treatment group . ( 4 ) Lumbar spine radiography is not cost-effective compared with usual care without lumbar spine radiography . DESIGN A r and omised unblinded controlled trial . SETTING Seventy-three general practice s in Nottingham , North Nottinghamshire , Southern Derbyshire , North Lincolnshire and North Leicestershire . Fifty-two practice s recruited participants to the trial . SUBJECTS R and omised arm : 421 participants with low back pain , with median duration of 10 weeks . Patient preference arm : 55 participants with low back pain , with median duration of 11 weeks . INTERVENTION Lumbar spine radiography and usual care versus usual care without radiography . MAIN OUTCOME MEASURES Rol and adaptation of the Sickness Impact Profile , visual analogue pain scale , health status scale , EuroQol , use of primary and secondary care services , and physical and complementary therapies , sickness absence , medication use , patient satisfaction , reassurance and belief in value of radiography at 3 and 9 months post-r and omisation . RESULTS Participants r and omised to receive an X-ray were more likely to report low back pain at 3 months ( odds ratio ( OR ) = 1.56 ; 95 % confidence interval ( CI ) , 1.02 to 2.40 ) and had a lower overall health status score ( p = 0.02 ) . There were no differences in health or functional status at 9 months . A higher proportion of participants consulted the general practitioner ( GP ) in the 3 months following an X-ray ( OR = 2.72 ; 95 % CI , 1.80 to 4.10 ) . There were no differences in use of any other services , medication use or sickness absence at 3 or 9 months . No serious spinal pathology was identified in either group . The commonest X-ray reports were of discovertebral degeneration and normal findings . Many patients did not perceive their information needs were met within the consultation . Satisfaction with care was greater in the group receiving radiography at 9 months . Participants r and omised to receive an X-ray were not less worried , or more reassured about serious disease causing their low back pain . Satisfaction was associated with meeting participants ' information needs and reduced belief in the necessity for investigations for low back pain , including X-rays and blood tests . In both groups , at 3 and 9 months 80 % of participants would choose to have an X-ray if the choice was available . Participants in the patient preference group achieved marginally better outcomes than those r and omised to a treatment group , but the clinical significance of these differences is unclear . Lumbar spine radiography was associated with a net economic loss at 3 and 9 months . CONCLUSIONS Lumbar spine radiography in primary care patients with low back pain of at least 6 weeks duration is not associated with improved functioning , severity of pain or overall health status , and is associated with an increase in GP workload . Participants receiving X-rays are more satisfied with their care , but are not less worried or more reassured about serious disease causing their low back pain . CONCLUSIONS - RECOMMENDATIONS FOR FURTHER RESEARCH : Further work is required to develop and test an educational package that educates patients and GPs about the utility of radiography and provides strategies for identifying and meeting the information needs of patients , and the needs of patients and GPs to be reassured about missing serious disease . Guidelines on the management of low back pain in primary care should be consistent about not recommending lumbar spine radiography in patients with low back pain in the absence of red flags for serious spinal pathology , even if the pain has persisted for at least 6 weeks Objective This study is design ed to investigate the role of written information , and the value of its timing , provided to Emergency Department ( ED ) patients regarding cardiac enzyme tests ( CET ) , on their personal concerns about their health status and their discussion s with the emergency physicians as to their normal health status post-test . Material s and methods This is a prospect i ve r and omized controlled study . All consecutive patients used for this study were admitted to the university-based ED within the 6-month study period with the presenting chief complaint of atypical chest pain , which was considered as the presumptive diagnosis . CET was ordered to rule out acute coronary syndromes , and these patients were enrolled into the study groups . Results The study sample included 523 patients whose CET were ordered and who were therefore eligible for the study . Three groups were similar in terms of persuasion and anxiety scores . Groups , which were informed about the test by leaflet had lower anxiety and persuasion scores . The lowest anxiety scores were found especially in the group in which the information was given before CET was drawn ( P<0.001 ) . The effects of monitoring on patients and providing information with a leaflet were found significant on reassurance scores ( P=0.006 , P<0.001 ) . Reassurance scores of the patients on whom at least one of the procedures , for example , monitoring , more than one electrocardiogram and chest radiograph , had been carried out , showed significant difference compared with those on whom neither of these procedures had been done during the ED observation ( P=0.001 ) . Conclusion Written information provided to patients undergoing cardiac tests in ED population was found effective on anxiety and persuasion scores BACKGROUND It is unclear whether normal endoscopy results in patients investigated for dyspepsia has therapeutic value . Therefore the aim of this study was to evaluate the effect of the endoscopy on quality of life and dyspeptic symptoms . METHODS One hundred ninety-six symptomatic patients ( 85 men and 111 women , mean age 42.9 years ) , who were receiving no treatment , were investigated before and 1 week after endoscopy with the use of a battery of vali date d question naires . RESULTS Before endoscopy the health-related quality of life was compromised in comparison with a normal population , but 1 week after a negative endoscopy it is increased to a level which was close to the normal range despite no major change in symptoms . Physical activity and sleep scores improved significantly after endoscopy . CONCLUSION The present results suggest that a negative endoscopy improves quality of life in the short-term in patients with dyspepsia , even though symptoms may persist |
12,115 | 25,431,843 | No evidence of differences was found between tissue adhesives and tapes for minimising dehiscence , infection , patients ' assessment of cosmetic appearance , patient satisfaction or surgeon satisfaction .
There appeared to be little difference in outcome for different types of tissue adhesives .
One study that compared high viscosity with low viscosity adhesives found that high viscosity adhesives were less time-consuming to use than low viscosity tissue adhesives , but the time difference was small .
Sutures are significantly better than tissue adhesives for minimising dehiscence .
In some cases tissue adhesives may be quicker to apply than sutures . | BACKGROUND Sutures ( stitches ) , staples and adhesive tapes have been used for many years as methods of wound closure , but tissue adhesives have entered clinical practice more recently .
Closure of wounds with sutures enables the closure to be meticulous , but the sutures may show tissue reactivity and can require removal .
Tissue adhesives offer the advantages of an absence of risk of needlestick injury and no requirement to remove sutures later .
Initially , tissue adhesives were used primarily in emergency room setting s , but this review looks at the use of tissue adhesives in the operating room/theatre where surgeons are using them increasingly for the closure of surgical skin incisions .
OBJECTIVES To determine the effects of various tissue adhesives compared with conventional skin closure techniques for the closure of surgical wounds . | BACKGROUND While a variety of epidermal wound closure techniques are utilized , there are few evidence based studies comparing techniques in head-to-head studies . OBJECTIVE To compare the aesthetic outcomes and wound healing properties of 2 epidermal closure mechanisms : 2-octylethylcyanoacrylate adhesive and rapid absorbing gut suture in skin closures . METHODS A total of 8 patients were enrolled in this r and omized right-left comparative trial . Patients were r and omized for epidermal closure with one half of their wounds ( chest [ n=6 ] and upper extremities [ n=2 ] ) with tissue adhesive and the contralateral with rapid absorbing gut suture . RESULTS Three months following wound closure , overall cosmetic outcome was slightly greater on the half closed with rapid absorbing gut suture ( mean=3.56 ) relative to the tissue adhesive ( mean=3.19 , P=.05 ) . For dyspigmentation , the half of the scar treated with the suture had a better outcome ( mean=3.50 ) relative to tissue adhesive ( mean=2.75 ) ( P<.05 ) . All other variables ( i.e. , scar thickness , wound approximation , patient outcome , and preference ) were highly equivalent . CONCLUSION Both rapid absorbing gut suture and tissue adhesive appear to be highly efficacious techniques for epidermal closure . It appears that tissue adhesive may not be as effective in achieving optimal cosmesis for defects after Mohs micrographic surgery on the trunk and extremities in follow-up at 3 months Traditional skin sutures ( TSS ) and metal skin clips ( SC ) are the most common devices utilized for closure of surgical incisions . They are safe and effective , although they require instruments to apply them , are time consuming and , above all , create an extra staff and cost burden for removal of sutures/staples . The ideal incision closure should be simple , effective , safe , rapid , inexpensive , painless , cosmetic and bactericidal . The present study was design ed to determine the safety and efficacy of N-butyl octyl cyanoacrylate ( NCA ) tissue adhesive , a liquid b and age surgical product , for wound closure in brain surgery . Our prospect i ve r and omized controlled study compared NCA with traditional methods for wound closure in brain surgery . Over a 6-month period , 40 patients who underwent a supratentorial elective craniotomy were enrolled and r and omly allocated into two groups . The 20 participants in group A were treated using a new NCA tissue adhesive while the 20 participants in group B were treated using either nylon monofilament , TSS or SC . In the post-operative period and during follow-up , two different nurses ( the second nurse was blinded to the closure method used ) recorded details regarding wound aspects , complications and patient satisfaction using a modified version of the Holl and er Wound Score Scale . We found no difference in the cosmetic outcome of the two groups , or in wound complications rate , but the patient satisfaction score was higher in group A ( 9.4 vs. 7.1 ; p<0.005 ) . The mean application time of the tissue adhesive was significantly faster than that of the st and ard suture ( 115s vs. 300s ; p<0.001 ) ; in the skin clips subgroup it was 105s . Our study suggests that the new NCA tissue adhesive is a safe , effective and reliable skin closure for neurosurgical procedures in the supratentorial region ; it also achieves optimal cosmetic results , is less time consuming to use and has greater patient satisfaction . However , further studies with a larger number of patients are necessary to corroborate these results OBJECTIVE To compare the surgical efficacy and wound-healing characteristics of the tissue adhesive octyl-2-cyanoacrylate ( approved by the Food and Drug Administration ) with traditional suture closure in upper blepharoplasty . METHODS Prospect i ve , r and omized , blinded study comparing cosmetic and functional outcome and time efficiency . Twenty subjects underwent upper eyelid blepharoplasty . Each patient had a control side and an experimental side determined r and omly . One eyelid incision was closed with octyl-2-cyanoacrylate ( Dermabond ; Ethicon Inc , Somerville , NJ ) tissue glue , and the other with 6.0 suture ( polypropylene or fast-absorbing gut ) . Comparisons were performed for the time for closure by each method , wound healing , and patient satisfaction . Macrophotographs of the wounds at 1 , 2 , and 4 weeks after surgery were grade d by 5 observers blinded to the closure method , using a 10-point scale and a modified Holl and er wound evaluation scale . RESULTS No statistically significant difference was found between the quality of octyl-2-cyanoacrylate closure and suture closure at 1 month . There were no differences in wound complications , duration of healing , inflammation , or final incision appearance . By 2 weeks , the sides were indistinguishable in 15 ( 75 % ) of the patients . Time for closure averaged 7 minutes with suture and 8 minutes with glue . CONCLUSIONS Octyl-2-cyanoacrylate glue is an excellent alternative to suture closure , producing equivalent quality of closure at all time points and no difference in appearance . This adhesive was sufficient to withst and the forces of closure in upper eyelid blepharoplasty without dehiscence in the absence of sutures BACKGROUND Topical 2-octylcyanoacrylate tissue adhesive is an alternative to traditional devices for closing short surgical incisions . METHODS An open-label , r and omized study compared a new high-viscosity formulation of 2-octylcyanoacrylate with commercially available devices , including low-viscosity 2-octylcyanoacrylate , for epidermal closure of incisions > or = 4 cm requiring subcutaneous and /or deep-dermal suturing . RESULTS Of patients with 1 to 3 wounds , 106 were treated with high-viscosity 2-octylcyanoacrylate and 103 with commercially available devices . The day-10 rates of healing by wound were 96 % and 97 % for study versus control treatment and 97 % and 95 % for new and old 2-octylcyanoacrylate formulations versus other controls , respectively . Day-10 infection rates by wound were 4 of 145 versus 7 of 131 for study versus control treatment and 6 of 207 and 5 of 69 for new and old 2-octylcyanoacrylate versus other controls , respectively . CONCLUSIONS The new tissue adhesive formulation provides epidermal wound closure equivalent to commercially available devices with a trend to decreased incidence of wound infection STUDY OBJECTIVE To compare the 1-year cosmetic outcome of wounds treated with octylcyanoacrylate tissue adhesive and monofilament sutures and to correlate the early , 3-month , and 1-year cosmetic outcomes . METHODS We prospect ively r and omized 136 cases of traumatic laceration to repair with octylcyanoacrylate tissue adhesive or 5 - 0 or smaller monofilament suture . A wound score was assigned by a research nurse , and vali date d by a second nurse blinded to the treatment , at 5 to 10 days after injury ( early ) , 3 months , and 1 year . St and ardized photographs were taken at 3 months and 1 year and shown to a cosmetic surgeon blinded to the method of closure , who rated the wounds on a vali date d cosmesis scale . RESULTS We were able to examine 77 lacerations at 1 year for follow-up . No differences were found in the demographic or clinical characteristics between groups . Likewise , at 1 year no difference was found in the optimal wound scores ( 73 % versus 68 % , P = .60 ) or in visual analog scale cosmesis scores ( 69 versus 69 mm , P = .95 ) for octylcyanoacrylate and sutures , respectively . Agreement was poor between early and 3-month wound scores ( kappa=.34 ; 95 % confidence interval [CI],.10 to.58 ) but a strong association existed between 3-month and 1-year wound scores ( kappa=.71 ; 95 % CI,.52 to.90 ) . We noted a moderate correlation between 3-month and 1-year results on the visual analog cosmesis scale ( intraclass correlation,.48 ; 95 % CI , .30 to.63 ) . CONCLUSION One year after wound repair , no difference is noted in the cosmetic outcomes of traumatic lacerations treated with octylcyanoacrylate tissue adhesive and sutures . The assessment of wounds 3 months after injury and wound repair provides a good measure of long-term cosmetic outcome BACKGROUND Wound closure devices include sutures , tissue adhesives , adhesive strips , and staples . Recent studies suggest no differences between various tissue adhesives and sutures for dehiscence , infection , and satisfaction when assessed by patients or surgeons . To date , no studies have investigated ClozeX ( Clozex Medical LLC , Wellesley , MA , USA ) , a novel adhesive strip , for closure of surgical incisions . OBJECTIVE To compare surgical wounds repaired with ClozeX versus suture . METHODS A prospect i ve , r and omized study was conducted , in which 15 patients with surgical incisions were allocated to closure with ClozeX on half of the wound and monofilament suture on the other half . Physician satisfaction with blinded assessment , patient satisfaction , complication rates , and closure times were recorded . RESULTS Application with ClozeX was faster than with suture ( p=.007 ) . There were no complications in either group . Sixty-nine percent of the patients gave ClozeX a higher satisfaction score ( p=.02 ) . More physicians were satisfied with the ClozeX half than with the suture half ( p=.007 ) . CONCLUSIONS This pilot study demonstrates ClozeX to be a safe and effective closure device . The cosmetic outcome seems to be at least as good as simple running suture . Physicians and patients were generally more satisfied with ClozeX. No difference was found in the rate of dehiscence or infection between the groups A r and om study for management of wound by cyanoacrylate glue in 213 patients , irrespective of age and sex with different types of wounds was carried out over a period of 4 years ( 1996 - 2000 ) . In this series both dean surgical wounds and infected accidental wounds were included . Most of the patients recovered uneventfully , except 5 , who showed wound gap . Reapplication of glue was done on them and 3 had similar wound union but 2 patients ( 0.94 % ) required surgical suture Background Topical 2-octylcyanoacrylate tissue ( OCA ) adhesive has been used as an alternative to close wounds with a comparable cosmetic outcome . The use of 2-OCA in the closure of abdominal laparotomy wounds has not been thoroughly evaluated . Our aim was to compare 2-OCA with conventional skin stapling devices in colorectal surgery . Methods A prospect i ve r and omised study was conducted in which 74 consecutive patients above the age of 21 undergoing open elective colectomies for benign or malignant indications were allocated to skin closure with 2-OCA or skin staples . Cosmetic outcome as assessed with the Holl and er Cosmesis Scale with a single assessor , complication rates , and patient satisfaction were recorded at discharge ( 4–10POD ) 2 weeks after discharge and then at 3 months . Results Of the 74 patients , 38 were r and omised to skin staples and 36 to 2-OCA . There was no significant difference in cosmetic outcomes between the two groups as assessed with a visual analogue scale or the Holl and er Cosmesis Scale but showed a trend to better cosmetic outcomes in the 2-OCA group . Patient satisfaction scores were higher but did not reach statistical significance . The time taken to close a wound with 2-OCA was significantly longer than with skin staples . There was no statistical difference in rates of wound infection . Conclusion 2-OCA is a safe and effective means of skin closure in patients undergoing elective colectomies with a good and at least equivalent outcome to traditional methods of closure PURPOSE In this study , we compared the skin adhesive 2-octylcyanoacrylate to subcuticular suture for closure of pediatric inguinal hernia incisions to determine if skin adhesive improves wound cosmesis , shortens skin closure time , and lowers operative costs . METHODS We prospect ively r and omized 134 children undergoing inguinal herniorrhaphy at our institution to have skin closure with either skin adhesive ( n = 64 ) or subcuticular closure ( n = 70 ) . Data collected included age , sex , weight , type of operation , total operative time , and skin closure time . Digital photographs of healing incisions were taken at the 6-week postoperative visit . The operating surgeon assessed cosmetic outcome of incisions using a previously vali date d visual analog scale , as well as an ordinate scale . A blinded assessment of cosmetic outcome was then performed by an independent surgeon comparing these photographs to the visual analog scale . Operating room time and re source use ( ie , costs ) relative to the skin closure were assessed . Comparisons between groups were done using Student 's t tests and chi(2 ) tests . RESULTS Children enrolled in the study had a mean + /- SE age of 3.7 + /- 0.3 years and weighed 16 + /- 0.8 kg . Patients were predominantly male ( 82 % ) . Patients underwent 1 of 3 types of open hernia repair as follows : unilateral herniorrhaphy without peritoneoscopy ( n = 41 ; 31 % ) , unilateral herniorrhaphy with peritoneoscopy ( n = 55 ; 41 % ) , and bilateral herniorrhaphy ( n = 38 ; 28 % ) . Skin closure time was significantly shorter in the skin adhesive group ( adhesive = 1.4 + /- 0.8 minutes vs suture = 2.4 + /- 1.1 minutes ; P = .001 ) . Mean wound cosmesis scores based on the visual analog scale were similar between groups ( adhesive = 78 + /- 21 ; suture=78 + /- 18 ; P = .50 ) . Material costs related to herniorrhaphy were higher for skin adhesive ( adhesive = $ 22.63 vs suture = $ 11.70 ; P < .001 ) , whereas operating room time costs for adhesive skin closure were lower ( adhesive = $ 9.33 + /- 5.33 vs suture = $ 16.00 + /- 7.33 ; P < .001 ) . Except for a 7 % incidence of erythema in both groups , there were no complications encountered . CONCLUSIONS There is no difference in cosmetic outcome between skin adhesive and suture closure in pediatric inguinal herniorrhaphy . Material costs are increased because of the high cost of adhesive relative to suture . This is partially offset , however , by the cost savings from reduction in operating room time Abstract .Tissue adhesives have gained favour for quicker and painless closure of lacerations . To compare the tissue adhesive 2-octylcyanoacrylate with our current st and ard subcuticular suture for closure of surgical incisions in children , looking at outcome measures of time efficiency , cosmesis , and wound complications , a prospect i ve , r and omised , controlled trial was conducted at our institution 's ambulatory surgery centre . All healthy patients undergoing unilateral or bilateral herniotomies were recruited prospect ively with informed consent and r and omly allocated to suture or glue . The exclusion criteria were neonates or children with allergy to tissue glue . Time of wound closure was measured from the subcutaneous layer to application of the dressing . An independent , blinded observer assessed cosmesis at 2 to 3 weeks using a vali date d wound scale ranging from worst ( 0 ) to best ( 6 ) . Parent satisfaction with wound appearance was recorded on a 100-mm visual analogue scale ( VAS ) . A total of 59 patients were recruited into the study with 26 in the glue group and 33 in the suture group . There was no difference in mean time of closure ( glue 181 ± 62 s vs suture 161 ± 45 s , P = 0.18 ) . Two patients in each group had a suboptimal Holl and er wound score of 5 ( 7.7 % glue , 6.1 % suture ) . There was also no difference in parent satisfaction ( VAS : glue 78 ± 19 mm vs suture 81 ± 15 mm , P = 0.68 ) . No patient reported any rash , wound infection , or dehiscence . Tissue glue is easy to use with no complications and has equivalent cosmetic results , but is not faster than a subcuticular suture Objective : The aim of this study was to evaluate the efficiency of two local hemostatic agents administered with apreoperative dose of replacement therapy in patients with bleeding disorders undergoing oral surgery . Material and Methods : The study included 21 patients that were r and omly divided into 3 groups . Patients in Group1 ( n = 7 ) received preoperative replacement therapy and postoperative fibrin sealant applied to the surgical site . Patients in Group 2 ( n = 7 ) received preoperative replacement therapy and postoperative tissue adhesive applied to the surgicalsite . Patients in Group 3 ( n = 7 ) were given replacement therapy pre- and postoperatively . Results : Postoperative bleeding was not observed in 17 of the 21 patients , including 5 in Group 1 ( 71.42 % ) , 6 in Group2 ( 85.71 % ) , and 6 in Group 3 ( 85.71 % ) . Hemorrhagic complications occurred in only 4 of the 21 patients . Conclusion : The use of fibrin sealant and tissue adhesive was beneficial , as they reduced the level of factor concentratesused for replacement therapy and result ed in rapid hemostasis at the surgical site , facilitating the ability to performserial surgical procedures concurrently BACKGROUND 4 methods are used in pediatric laparoscopic surgery to close trocar wounds . While tissue adhesives or adhesive strips have been shown to produce fewer wound complications and a better cosmetic result compared to trans- or only subcutaneous sutures , the choice of technique is still often based on the surgeon 's personal experience . Thus , the objective of this trial was to assess the impact of tissue adhesives ( Dermabond ™ ) compared to adhesive strips ( Steri-Strip ™ ) on potential complications of wound healing , wound pain , cosmetic outcome , and patient satisfaction after laparoscopic appendectomy in children . METHODS 49 patients undergoing laparoscopic appendectomy were enrolled in this prospect i ve r and omized trial . In every patient , two 5-mm and one 10-mm port-site incision was closed either with Dermabond ™ or Steri-Strip ™ after placing subcuticular absorbable sutures ( 4 - 0 Vicryl ™ ) . Postoperative complications , pain , and patient satisfaction with scars were evaluated at follow-up on day 10 and day 90 after the operation using a question naire and a visual analogue scale ( VAS ) . Photographs of scars taken on day 90 were evaluated on a VAS by 2 pediatric surgeons blinded to the closure method used . RESULTS According to the surgeons ' evaluation of the cosmetic outcome , a significant difference between the 2 groups with regard to the cosmetic score was found on day 90 of follow-up , favoring Steri-Strip ™ wound closure ( p < 0.05 ) . On day 10 and 90 there were no statistical differences between the 2 methods as regards the result of patient evaluations ( p > 0.05 ) . Only one wound infection ( 4 % ) was observed in the Steri-Strip ™ group ( n = 25 ) on day 10 . At follow-up on day 90 two patients ( 9.1 % ) in the Dermabond ™ group and one ( 4.8 % ) in the Steri-strip ™ group complained of wound pain ( p = 0.52 ) . CONCLUSIONS Both tissue adhesives and adhesive strips are excellent " no needle " alternatives for the closure of laparoscopic port-site incisions in children . As regards cosmetic outcome , Steri-Strip ™ wound closure seems to be the most suitable and is also the less expensive technique We undertook a r and omised controlled trial to compare the outcomes of skin adhesive and staples for skin closure in total hip replacement . The primary outcome was the cosmetic appearance of the scar at three months using a surgeon-rated visual analogue scale . In all , 90 patients were r and omised to skin closure using either skin adhesive ( n = 45 ) or staples ( n = 45 ) . Data on demographics , surgical details , infection and oozing were collected during the in-patient stay . Further data on complications , patient satisfaction and evaluation of cosmesis were collected at three-month follow-up , and a photograph of the scar was taken . An orthopaedic and a plastic surgeon independently evaluated the cosmetic appearance of the scars from the photographs . No significant difference was found between groups in the cosmetic appearance of scars at three months ( p = 0.172 ) , the occurrence of complications ( p = 0.3 ) , or patient satisfaction ( p = 0.42 ) . Staples were quicker and easier to use than skin adhesive and also less expensive . Skin adhesive and surgical staples are both effective skin closure methods in total hip replacement STUDY OBJECTIVE To compare the tissue adhesive Histoacryl Blue with suturing in the repair of pediatric facial lacerations . DESIGN Prospect i ve , r and omized controlled trial . SETTING Emergency department of a pediatric teaching hospital . PARTICIPANTS Eighty-one children presenting with clean facial lacerations less than 4 cm in length and 0.5 cm in width . INTERVENTIONS Patients were allocated r and omly to have their lacerations repaired with sutures or Histoacryl Blue . RESULTS The two groups were similar for demographic and clinical characteristics . Photographs taken at three months were rated by two plastic surgeons blinded to the method of closure . There was no difference between groups for appearance scores on a visual analog scale ( 60.5 mm for Histoacryl Blue versus 57.2 mm for suture , P = .45 ) or on a categorical scale ( Histoacryl Blue versus sutures : unacceptable , 11 % versus 13 % ; acceptable , 59 % versus 71 % ; excellent , 30 % versus 16 % ; P = .76 ) . Measures of observer agreement produced Pearson correlations of .72 and .94 on the visual analog scale and kappa coefficients of .46 and .73 on the categorical scale . Histoacryl Blue was assessed as less painful on a visual analog scale ( 24.7 versus 43.7 mm , P < .01 ) and faster ( 7.9 versus 15.6 minutes , P < .001 ) . CONCLUSION Histoacryl Blue is a faster and less painful method of facial laceration repair that has cosmetic results similar to the use of sutures AIMS Wound healing is a major determent in the post-surgical course of patients ( pts ) after pacemaker ( PM ) and implantable cardioverter defibrillator ( ICD ) implantation . Insufficient closure may lead to serious complications with pocket infections leading to the device 's explantation as the worst case scenario . In addition to the different types of suture and suture clips , a novel topical skin adhesive containing 2-octyl-cyanoacrylate is commercially available . METHODS AND RESULTS Over a period of 18 months , we prospect ively assigned all cases of PM , ICD , and loop recorder implants either to skin adhesive ( Group 1 ) or to absorbable intracutaneous polydioxanon suture ( Group 2 ) . Data were analysed with respect to operation time , wound infections , and healing disorders . One hundred and eighty-three pts were r and omized into Group 1 [ 71 PMs , 60 ICD , 15 cardiac resynchronization therapy ( CRT ) , 11 loop recorders , and 26 generator replacements ] . One hundred and eighty-five pts were assigned to Group 2 ( 62 PMs , 70 ICD , 30 CRT , 7 loop recorders , and 16 generator replacements ) . There were no differences regarding sex , diabetes , renal insufficiency , corticosteroid therapy , oral anticoagulants , and acetylsalicylic asa/clopidogrel ( P = n.s . ) . For the significantly higher amount of CRT devices ( P < 0.05 ) in Group 2 , the procedure times are given for surgeries except CRT . It was 49.1 ± 27.7 min for Group 1 and 53.4 ± 31.9 min for Group 2 ( P = n.s . ) . Adverse events as insufficient closure , major and minor bleeding , pocket haematoma , erythema , incrustation , dehiscence , keloid , and explantation due to infection occurred significantly more often in the adhesive group ( P = 0.02 ) . The greatest impact on this result had early adverse events as insufficient closure , wound incrustation , and inflammation ( 9.3 vs. 6.0 % ; P = 0.02 ) . We did not find any difference in long-term adverse events , infections in particular ( 2.7 vs. 1.6 % ; P = 0.47 ) . CONCLUSION This study shows no benefit using skin adhesive in comparison to absorbable intracutaneous suture regarding surgery times for the implantation of cardiac rhythm devices . The rate of early adverse events after wound closure is higher after skin adhesive but no difference in long-term adverse events occurred OBJECTIVE Bleeding and wound infection are the most common complications of circumcision . Cyanoacrylate tissue glue has been cl aim ed to have the advantage of being haemostatic , bacteriostatic and easy to use . The purpose of this study is to assess the feasibility of using the tissue glue in approximation of circumcision wound in children . METHODOLOGY A prospect i ve r and omized trial was carried out on 86 boys consecutively admitted into the Duchess of Kent Children 's Hospital , Hong Kong . The results of wound approximation with cyanoacrylate tissue glue and suturing with interrupted 4/0 plain catgut were compared . The operations were carried out by the same surgeon using identical technique except for the wound approximation . The wound was assessed 1 day , 2 days , 3 days , 1 week and 1 month postoperatively . RESULTS There was no statistically significant difference between the two groups in the rates of wound inflammation , infection , bleeding , dehiscence and cosmetic appearance , but the duration of operation was longer using tissue glue ( 19.8 min vs 16.5 min , P = 0.002 ) . CONCLUSIONS We conclude that tissue glue approximation of circumcision wounds in children is a feasible alternative , but it offers no extra advantage when compared to suturing 2-Octylcyanoacrylate tissue adhesive ( Dermabond , Ethicon , Inc , Somerville , NJ ) is being used successfully for closure of minor lacerations . To date , however , there have been no studies evaluating its use in the operating room for surgical incisions . We conducted a prospect i ve r and omized trial to compare the closure of inguinal herniorrhaphy incisions using 2-octylcyanoacrylate tissue adhesive ( Dermabond ) with closures using 4 - 0 Monocryl ( Ethicon , Inc ) in a running subcuticular closure . A total of 46 incisions were r and omized at the time of closure . Of these incisions 24 were r and omized to Dermabond closure ( TA ) and 22 were r and omized to subcuticular closure ( SC ) . Performance measures included : time for closure , wound complications , and cosmesis . Cosmesis was evaluated by blinded evaluation of photographs of the incisions taken 4 weeks after surgery . Closure times for the TA group were faster than in the SC group ( mean of 155 vs 286 seconds ; P < 0.001 ) . Wound complications were higher in the TA group ( P = 0.045 ) . Cosmesis was also felt to be better in the SC group with a score of 4.2 versus 3.88 , but this did not reach statistical significance . Although the use of Dermabond did result in faster wound cultures it also result ed in an increase in wound complications . The difference in mean cosmetic score for each group was not statistically significant but trended toward better scores in the SC group . Based on these findings we do not feel Dermabond is an acceptable alternative to subcuticular suture closure in inguinal herniorrhaphy incisions STUDY OBJECTIVE More than 11 million patients with traumatic wounds are seen annually in emergency departments . We developed and vali date d a data registry for traumatic wounds treated in the ED . DESIGN Prospect i ve , consecutive patient enrollment with a validation cohort of a convenience sample of 100 patients . SETTING University-affiliated hospital ED . PARTICIPANTS For all patients with traumatic wounds requiring sutures , wound registry data sheets were completed at the time of initial visit using a closed- question format . Data recorded included demographic characteristics , time from injury to evaluation , pertinent medical history , wound characteristics , type of anesthesia , details of wound-cleansing methods , details of wound closure , and postoperative care . We devised a follow-up tool to evaluate for the presence of infection and short-term cosmetic appearance . Interphysician reliability was assessed for wound description , presence of infection , and cosmetic appearance by use of the kappa statistic . RESULTS A wound registry data collection instrument that takes less than 1 minute to complete and enables the collection of most wound management techniques used by emergency physicians was found to have substantial interobserver concordance for wound description ( kappa range , .55 to .97 ) , wound infection ( kappa = 1.0 ) and overall cosmetic appearance ( kappa = .61 ) . CONCLUSION The wound registry is a reliable data collection instrument that is easy to use . It may be useful as a continuous quality -improvement tool or for st and ardization of wound surveillance and treatment data to facilitate future prospect i ve studies in wound management Objective . Surgical repair of perineal lesions after delivery is frequently associated with pain and discomfort , interfering with the normal activities of the puerperium . The aim of this study was to compare perineal skin repair after episiotomy with adhesive glue versus a subcuticular suture , regarding the incidence of pain and wound complications . Study design . R and omized clinical trial . Setting . Tertiary care university hospital . Material and methods . One hundred women having mediolateral episiotomy at vaginal delivery were enrolled . They were r and omized to receive skin adhesive ( n = 53 ) or subcuticular suture ( n = 47 ) for closure of perineal skin . The main outcome measure was self‐evaluated pain in the 30 days following delivery . Secondary outcome measures were technical difficulties reported with the procedure , duration of surgical repair , wound complications observed at 42–68 hours post‐partum and re‐initiation of sexual activity by 30 days post‐partum . Results . No significant differences were observed between the two groups in incidence of technical difficulties and failed procedures , pain during the procedure , wound complications at hospital discharge , self‐evaluated measures of pain at 7 and 30 days or re‐initiation of sexual activity by 30 days post‐partum . The skin adhesive group had a significantly shorter mean duration of the procedure ( four minutes less ) . Conclusion . Perineal skin closure using adhesive glue is faster than subcuticular suture , and associated with a similar incidence of complications and pain in the first 30 days Four wound closure techniques for total knee arthroplasty were compared in a prospect i ve , r and omized , controlled , institutional review board-approved study with 75 subjects . The study compared tissue adhesives , stapling , and suturing with respect to procedure time and cost , together with functional and clinical outcome . Total knee arthroplasty closure time ( capsule to cutaneous ) favored staples at 26 s/cm , followed by adhesives ( 45 and 37 s/cm for 2-octyl and n-butyl-2 , respectively ) and , finally , subcuticular suturing at 54 s/cm ( P < .0007 ) . Reduced procedure time translated into intraoperative cost reduction where closure cost per centimeter was $ 70 , $ 62 , $ 57 , and $ 75 for 2-octyl , n-butyl-2 , staples , and sutures , respectively . No significant differences in infection , dehiscence , cosmesis , general health ( SF-12v2 ( Quality Metric Inc. , Lincoln , RI ) ) , and functional and clinical assessment s ( range of motion , Knee Society knee score , and pain ) were observed We carried out a blinded prospect i ve r and omised controlled trial comparing 2-octylcyanoacrylate ( OCA ) , subcuticular suture ( monocryl ) and skin staples for skin closure following total hip and total knee arthroplasty . We included 102 hip replacements and 85 of the knee . OCA was associated with less wound discharge in the first 24 hours for both the hip and the knee . However , with total knee replacement there was a trend for a more prolonged wound discharge with OCA . With total hip replacement there was no significant difference between the groups for either early or late complications . Closure of the wound with skin staples was significantly faster than with OCA or suture . There was no significant difference in the length of stay in hospital , Holl and er wound evaluation score ( cosmesis ) or patient satisfaction between the groups at six weeks for either hips or knees . We consider that skin staples are the skin closure of choice for both hip and knee replacements Fifty patients underwent a variety of h and operations and were r and omized for wound closure either with tissue adhesive ( Indermil ) or sutures . The two treatment groups had similar demographic characteristics and similar outcomes at the 2 and 6 week postoperative assessment s which were performed by a design ated tissue viability nurse blinded to the method of closure . Five minor wound dehiscences occurred : three in the adhesive group and two in the suture group . No infection occurred in either group . In conclusion , the study demonstrates tissue adhesive is as effective as suture in this type of h and surgery Current surgical management of deep partial-thickness and full-thickness burn wounds involves early excision and grafting . Blood loss during these procedures can be profound , thus prompting the use of topical hemostatic agents to control and minimize hemorrhage during grafting . The primary endpoint of this multicenter trial was to evaluate the efficacy of fibrin sealant as a topical hemostatic agent during skin grafting . The secondary endpoint was to obtain data to support the existing safety profile of a human fibrin sealant ( FS ) in participating patients as indicated by the type , severity , and frequency of any adverse events within the 24-hour postoperative period . A multicenter prospect i ve , open label , Phase III multicenter , r and omized , comparative clinical trial evaluated the use of fibrin sealant in burn patients undergoing skin graft procedures . Each patient served as his or her own control in this r and omized , unblinded study of the effect on time to hemostasis in donor sites treated with the investigational FS product . At operation , 1 contiguous donor skin harvest site was bisected into 2 equal halves , 1 of which was then r and omly selected and treated with fibrin sealant . At the end of the fibrin sealant application , the time to hemostasis in each of the donor site halves was identified by the operating surgeon and recorded by the research coordinator . The use of any other topical hemostatic agents was prohibited . A significant difference ( P < .001 ) was demonstrated in the mean time to hemostasis between the fibrin sealant treated donor sites when compared painwise to the control sites . The significant difference was consistent across the 6 participating study centers . There were no adverse events associated with the use of fibrin sealant . The investigational FS product was shown to be efficacious , because it significantly decreases the time to hemostasis at the donor skin harvest site in patients undergoing skin grafting and was noted not to cause any adverse reactions The aim of this study was to compare the efficacy of n-butyl-cyanoacrylate tissue adhesive ( Liquib and ) with nonabsorbable monofilament sutures for laparoscopic port site closure . Adult patients having elective laparoscopic procedures were r and omly allocated to wound closure with sutures or tissue adhesive . End points included skin closure time , wound dressing requirements , wound complications , and cosmesis , assessed at discharge , 4 to 6 weeks and 3 months . Seventy-eight patients r and omized to receive sutures and 76 to receive tissue adhesive were eligible for final analysis . Mean closure time was significantly longer for sutures ( 220 vs. 125 s , P<0.001 ) . Fewer dressings were required in the tissue adhesive group immediately postoperatively ( 21 % vs. 97 % , P<0.001 ) and at discharge ( 24 % vs. 82 % , P<0.001 ) . There were no significant differences in wound complications or in cosmesis at either 4 to 6 weeks or at 3 months . Tissue adhesive for laparoscopic port site closure offers potential savings with respect to time and has comparable wound complication rates and cosmetic outcomes when compared with nonabsorbable monofilament sutures Cosmetic outcome of the columellar incision closure in external rhinoplasty patients has been a subject of discussion . This study was conducted to assess whether tissue adhesives provide an alternative option for sutureless closure of columellar skin incisions for cases utilizing open technique rhinoplastic surgery . One hundred and one patients undergoing external rhinoplasty were r and omized to either topical application of butylcyanoacrylate or polypropylene sutures for columellar skin closure . The majority of tension on the wound edges was taken up using 5 - 0 chromic catgut . Cosmetic outcomes were evaluated by two otolaryngologists independently using visual analogue and Holl and er wound evaluation scales in a blinded manner . There was no statistically significant difference in cosmesis between the surgeons ' evaluation scores for either type or repair of the columellar incision . Since the tissue adhesive forms its own protective barrier , post-operative care is simplified . Closure with adhesives eliminates the need for post-operative suture removal requiring an extra visit that should lead to more efficient use of physician and patient time . Butylcyanoacrylate performs cosmetically as well as st and ard suture closure of columellar skin incision used for external rhinoplasty OBJECTIVE To assess the effectiveness of a new tissue adhesive for laceration closure . DESIGN A prospect i ve , r and omized controlled trial . SETTING An adult teaching hospital . PARTICIPANTS One hundred thirty patients with 136 lacerations who consented to enrollment during a 5-month period . The lacerations included all eligible nonmucosal facial lacerations , as well as selected extremity and torso lacerations ( not on h and s , feet , or joints ) . One hundred six lacerations were available for early follow-up , and 98 were available for 3-month evaluation . INTERVENTIONS Lacerations were r and omly allocated to have skin closure with octylcyanoacrylate adhesive or monofilament suture . MAIN OUTCOME MEASURE A 3-month photograph of the wound was assigned a cosmesis score on a previously vali date d 100-mm visual analog cosmesis scale by a plastic surgeon who was unaware of the method of wound closure . RESULTS There were no differences in the mean visual analog cosmesis scores ( 67 mm for octylcyanoacrylate vs 68 mm for sutures ; P=.65 ) . Similarly , there was no difference in the percentage of early ( 80 % vs 82 % ; P=.80 ) or late ( 72 % vs 75 % ; P=.74 ) optimal wound evaluation scores . The tissue adhesive was a faster method of wound repair ( 3.6 vs 12.4 minutes ; P<.001 ) as well as being less painful ( visual analog pain scores , 7.2 vs 18.0 mm ; P<.001 ) . CONCLUSIONS Octylcyanoacrylate tissue adhesive effectively closes selected lacerations . This relatively painless and fast method of wound repair can replace the need for suturing several million lacerations each year Acrylate glues used in a childrens ' day care unit to close small surgical wounds were compared . In 157 children , aged 12 weeks to 3.7 years , either Histoacryl or Dermabond was used ( respectively , H : Ethicon Inc. , Johnson & Johnson , NJ or D : Dermabond , Braun Surgical Gmbh , Melsungen , Germany ) . Operations were for inguinal hernia ( 110 cases ) , hydrocele ( 25 ) , undescended testis ( 16 ) , umbilical hernia ( 13 ) and funiculocele ( 3 ) . 1 week after surgery the wounds were evaluated in terms of integrity of closure , redness or infection , need for antibiotics , wound granuloma , and parental satisfaction with instructions and actual method of wound caring . 3 months after surgery the wound/scar was reexamined . The margins of the wounds were separated partially or completely in 8 of 85 in group H ( 9.4 % ) while in the D group , 2 wounds ( 2.4 % ) had partially opened ( p < 0.05 ) . There were no differences between the glues with regard to wound infection or cosmetic results . Parental satisfaction was higher with D ( 96 % ) than H ( 82 % ) but the difference was not statistically significant . It is convenient to use glue to close operative wounds in children after ambulatory surgery . The use of D significantly reduced wound ruptures compared to H. Long-term cosmetic results were similar Octyl-2-cyanoacrylate is a long carbon chain cyanoacrylate derivative that is stronger and more pliable than its shorter chain derivatives . One hundred and eleven patients underwent elective surgical procedures by the same surgeon using either octyl-2-cyanoacrylate or sutures for skin closure at the University of Illinois at Chicago . Most patients underwent excision of benign skin lesions with a mean wound size of 112 mm3 . Patients were r and omized into either control ( vertical mattress suture closure ) or test groups ( closure with octyl-2-cyanoacrylate ) . Surgical judgment was used to determine which wounds in each group required application of subcutaneous sutures to relieve tension and aid in skin edge eversion . Generally , full-thickness ( through dermis ) wounds larger than 1 cm3 required the use of subcutaneous sutures . The time required to close the epidermis with suture ( mean , 3 minutes and 47 seconds ) was about four times that of octyl-2-cyanoacrylate ( mean , 55 seconds ) . Wounds were evaluated at 5 to 7 days for infection , wound dehiscence , or tissue reaction , and at 90 days using the modified Holl and er wound evaluation scale . At 1 year , photographs of the wounds were evaluated by two facial plastic surgeons that grade d the cosmetic outcome using a previously vali date d visual analog scale . There were no instances of wound dehiscence , hematoma , or infection in either group . Results of wound evaluation at 90 days determined by the modified Holl and er scal revealed equivalent cosmetic results in both groups . Results of the visual analog scale ratings showed scores of 21.7 + /- 16.3 for the 49 patients treated with octyl-2-cyanoacrylate and 29.2 + /- 17.7 for the 51 control patients treated with sutures . The lower visual analog scale score represented a superior cosmetic outcome at 1 year with the octyl-2-cyanoacrylate as compared with sutures . This difference is statistically significant at p = 0.03 . Additionally , patient satisfaction was very high in the group treated with octyl-2-cyanoacrylate INTRODUCTION Cosmetic acceptability of scar and neck mobility are important outcomes after collar line incision for neck surgery . This r and omised , controlled trial compares these parameters in closures using tissue glue ( Dermabond , Ethicon , UK ) and skin staples . PATIENTS AND METHODS Patients requiring a collar line incision were r and omised to receiving tissue glue or staples for skin closure . Time for closure to be completed was recorded . Mobility of the neck was assessed using a visual analogue scale at 48 h and 1 week after surgery . At 6 weeks , cosmetic appearance was assessed using a linear 1 - 10 visual analogue scale by the patient , surgeon and an independent blinded assessor . Results were compared using appropriate statistical tests . RESULTS Glued ( n = 14 ) and stapled ( n = 15 ) closures were performed for hemithyroidectomy ( n = 8 versus 6 ) , sub-total thyroidectomy ( n = 2 versus 4 ) , total thyroidectomy ( n = 1 versus 4 ) and parathyroidectomy ( n = 3 versus 1 ) . Closure with tissue glue took significantly longer than with staples ( mean , 95 versus 28 s ; P < 0.001 ) . Neck mobility scores were comparable at 48 h and 1 week ( mean , 4.8 versus 4.4 ; P = 0.552 : and 2.7 versus 2.6 ; P = 0.886 ) . Cosmetic appearance at 6 weeks was comparable when patient ( mean , 1.7 versus 1.8 ; P = 0.898 ) , surgeon ( mean , 2.6 versus 2.3 ; P = 0.633 ) and independent assessment ( mean , 1.4 versus 1.9 ; P = 0.365 ) was performed . CONCLUSIONS The use of glued skin closure may increase the duration of surgery but acceptable neck mobility and wound cosmesis can be achieved by the more rapid application of stapled skin closure in cervicotomy incisions STUDY OBJECTIVE To compare LiquiB and Surgical S ( LB ) ( Advanced Medical Solutions Ltd , Plymouth , UK ) with High Viscosity Dermabond ( DB ) ( Ethicon Inc. , Kirkl and , Scotl and ) for the closure of laparoscopic wounds . DESIGN Prospect i ve , multicenter , r and omized , controlled trial ( Canadian Task Force classification I ) . SETTING Multiple district hospitals . PARTICIPANTS A total of 433 subjects were enrolled between 2006 and 2009 at 4 investigational sites . INTERVENTIONS In this study , LB , an octyl/butyl cyanoacrylate blend , and DB , an octyl-based cyanoacrylate , were compared for topical skin closure of laparoscopic port sites ( www . clinical trials.gov ; study identifier NCT00762905 ) . MAIN RESULTS High dermal apposition and cosmesis scores result ed from the use of both adhesives along with low rates of wound dehiscence and suspected infections . Masked evaluators and patients favored DB in the healing of the incisions ( 98.3 % DB vs 93.9 % LB , p < .05 ) and ( 97.2 % DB vs 89.4 % LB , p < .05 ) . However , there was no difference in the overall satisfaction of the appearance of the wounds . LB was found to be significantly ( p < .05 ) faster ( LB = 32.1 seconds ; DB , 50.3 seconds ) and easier to use than DB , and surgical users were significantly more satisfied with using LB for wound closure . CONCLUSION The results of this trial show the efficacy of LB for the closure of topical skin incisions ; LB was significantly faster , easier to use , and result ed in greater user satisfaction compared with DB OBJECTIVE To compare 2-octyl cyanoacrylate ( Dermabond ) with conventional suturing for closure of laparoscopic cholecystectomy ( LC ) wounds in a prospect i ve r and omized controlled trial . SUBJECTS Twenty-five consecutive patients underwent LC at a teaching hospital in the United Kingdom . Patients were r and omly allocated to have skin closed with 2-octyl cyanoacrylate or absorbable suture . METHODS Fifty-one wounds underwent skin closure with absorbable subcuticular suture ( 3/0 polydiaxanone ) and 48 wounds were closed with tissue adhesive . The time to close the wounds , including the placement of dressings , was recorded . At 6 to 8 weeks , the incisions were evaluated with the Holl and er wound evaluation scale ( HWES ) . Using a visual analogue scale ( VAS ) , the wounds were also rated by a plastic surgeon who was blinded to the method of closure . RESULTS The wounds were closed significantly faster in the Dermabond group ( mean 165 seconds versus 356 seconds , P = 0.03 ) . There were no differences in the percentage of wounds achieving optimal scores on the HWES ( suture 64.7 % versus tissue adhesive 60.4 % , P = 0.42 ) nor on the mean VAS ( suture 62 mm versus tissue adhesive 59 mm , P = 0.45 ) . CONCLUSION The tissue adhesive 2-octyl cyanoacrylate is a safe and fast method for closure of LC wounds , with cosmetic results comparable to suturing BACKGROUND The use of medical adhesives for topical wound closure is gaining in popularity over conventional wound closure material s such as sutures and staples . Adhesives provide advantages in both wound closure and patient management with good cosmetic outcome and surgeon and patient satisfaction reported . OBJECTIVE To compare the use of two currently marketed medical adhesives ; LiquiB and ® Flow Control and High Viscosity Dermabond ™ for the topical closure of surgical incisions . METHODS In a prospect i ve blinded manner , subjects were r and omly assigned LiquiB and ® or DermabondTM for topical closure of a surgical incision . Variables compared included ease of use , time taken to close wound , subject and surgeon satisfaction with device and wound closure , cosmetic outcome at 90 days , and complication rates . RESULTS Use of both devices result ed in effective wound closure with similar high levels of cosmesis subject and surgeon satisfaction , with only minor complications reported . There was no statistically significant difference between the devices for all the parameters studied , with the exception that the Liquib and device was found to significantly reduce the amount of time required for closure . CONCLUSION As the two devices appear substantially equivalent in terms of key surgeon and patient variables , product cost should be the primary determinant in selection of the tissue glue device BACKGROUND The purpose of this study is to determine whether closure of laparoscopic port-site incisions using octylcyanoacrylate ( OCA ) is feasible , whether it is faster than traditional subcuticular suturing , whether the number and length of incisions impact on closure time , and to determine wound morbidity and patient satisfaction outcomes . STUDY DESIGN A prospect i ve r and omized trial was performed on adult patients scheduled for elective laparoscopic surgery in three surgical specialties at a tertiary referral center . Patients were r and omized to have closure of laparoscopic port sites using either OCA or sutures . Patients were followed up 2 to 3 weeks postoperatively . At 2 months patients were mailed a question naire regarding their satisfaction with the method of closure and the appearance of their scars . RESULTS A total of 175 incisions in 50 patients were closed with OCA , and 142 incisions in 42 patients were closed with subcuticular sutures . Time to close was significantly faster for OCA ( median 2.5 minutes versus 6 minutes , p < 0.001 ) . OCA was faster than traditional subcuticular suturing for cases involving three or more port sites ( median 2.5 minutes versus 6 minutes , p < 0.001 ) , and for cases with total length of incisions > 4 cm ( median 2.6 minutes versus 7 minutes , p < 0.001 ) . OCA and subcuticular suturing groups did not differ significantly on patient acceptance or assessment of scars . CONCLUSIONS Closure of laparoscopic port-site incisions is feasible with OCA . Closure with OCA requires significantly less operative time than subcuticular suturing , particularly in cases when three or more port sites are used or when total incision length is greater than 4 cm . OCA appears to have equivalent adverse wound outcomes and patient acceptance rates as subcuticular suturing BACKGROUND Dermabond ( Ethicon UK , Edinburgh , United Kingdom ) is a topical skin adhesive used for surgical wound closure , with purported advantages over conventional sutures on cosmetic outcomes , cost benefits , and operative times . This study compared results of skin closure using Dermabond and subcuticular sutures after coronary artery bypass grafting ( CABG ) . METHODS The study prospect ively enrolled and r and omized 106 patients who underwent CABG . The groups received closure with Dermabond skin glue or subcuticular sutures ( n = 53 each ) after saphenous vein harvesting using the bridging technique . Wound closure time for the two methods was recorded . Cosmetic appearance was assessed using the Holl and er , the Vancouver , and the visual analog scale . Patient satisfaction was recorded before discharge and at week 6 . RESULTS There were no significant differences in the total operative time between the two groups ( p = 0.43 ) . Closure time was significantly shorter in the Dermabond group ( p = 0.017 ) . Patients in the Dermabond group also reported superior cosmetic outcome at weeks 1 ( p < 0.001 ) and 6 ( p = 0.001 ) and improved patient satisfaction ( p < 0.001 ) . CONCLUSIONS Dermabond has demonstrated superiority over traditional subcuticular skin sutures in terms of closure time , cosmetic appearance , and patient satisfaction . This technique provides a novel method of wound closure after CABG OBJECTIVE To determine the effectiveness of a tissue adhesive , Histoacryl Blue ( HAB ) , for laceration repair in children . DESIGN Prospect i ve , r and omized clinical trial . SETTING A tertiary care pediatric emergency center at Egleston Children 's Hospital . PARTICIPANTS Children who presented for laceration repair between October 1994 and February 1995 were prospect ively evaluated . Patients less than 1 or greater than 18 years of age , those with lacerations greater than 5 cm , and those with lacerations located on the eyelids , ears , nose , lips , h and s , feet , joints , or perineum were excluded . INTERVENTIONS Following consent and routine wound management , including subcutaneous closure when deemed necessary , patients were r and omized to receive skin sutures or HAB for cutaneous closure . METHODS Length of time required for laceration repair was recorded . Parental perception of the pain experienced by their child was assessed using a visual analogue scale . Photographic documentation of scar appearance at the 2-month follow-up visit was evaluated by plastic surgeons using a visual analogue scale . RESULTS Sixty-one children were enrolled : HAB group ( N = 30 ) , suture group ( N = 31 ) . No differences occurred between groups in laceration length , depth , location , or patient demographics . Length of time required for repair was decreased ( median , HAB 7 minutes vs suture 17.0 minutes ) and parental assessment of their child 's pain was significantly less in the HAB group . Parents were more likely to recommend HAB over suturing to other parents or guardians . Cosmetic outcome in the HAB group was assessed to be as good as , or better than , the cosmetic outcome in the suture group as evaluated by two plastic surgeons . CONCLUSION The use of HAB for laceration repair is an acceptable alternative to conventional suturing with a comparable cosmetic outcome . Advantages include less pain to the child , no need for suture removal , and more efficient use of physician time . Parents were also more likely to recommend HAB over suturing for laceration repair BACKGROUND The patient 's view of the outcome after phlebectomy is mainly dependent on the cosmetic result . OBJECTIVE To compare 5 - 0 monofilament sutures with tapes and tissue adhesive for wound closure after varicose vein surgery . METHODS Seventy-nine patients undergoing varicose vein surgery were prospect ively r and omized in three groups ( tissue adhesive , sutures , tape ) for skin closure and compared . The follow-up 1 year postoperatively was done by a senior dermatologist who was blinded in the method of skin closure . RESULTS The cosmetic outcome showed little advantage for the suture group . Taping the incisions is faster than suturing them but without significance ; closure with tissue adhesive takes nearly the double of time . The closure for one incision with tissue adhesive is 40 times more expensive than with tapes and 14 times more expensive than with sutures . CONCLUSION This study failed to demonstrate an advantage of tissue adhesive and tapes over monofilament sutures for skin closure after phlebectomy Objective : Closure of skin incision of minimally invasive thyroidectomy with tissue adhesive is compared with surgical staples for 1 ) cosmetic appearance , 2 ) patient pain score , and 3 ) patient satisfaction score . Study Design : Prospect i ve single-blinded r and omized study . Subjects and Methods : Seventy-two patients undergoing minimally invasive thyroid surgery using video-assisted thyroidectomy ( VAT ) and minimal incision thyroidectomy ( MIT ) techniques were r and omized for skin closure into two groups , one using staples and the other using tissue adhesive . Patients evaluated their pain on the first and tenth postoperative days . Scars were assessed using the Manchester scar assessment tool , and patients completed a satisfaction assessment form . Results : Sixty out of the 72 patients were followed up for three months postoperatively . Assessment of wound cosmesis revealed no statistical difference ; however , there was a statistical difference in ability to shower and overall satisfaction in the tissue adhesive group ( P = 0.017 ) . Conclusion : Tissue adhesive is an excellent alternative for skin incision closure , having the added advantage of ability to shower on the same day , avoidance of the anxiety associated with staple removal , and no General Practitioner ( GP ) visit required for wound care . The use of tissue adhesive achieves higher patient satisfaction levels and enhances the perception of minimally invasive thyroid surgery ( MITS ) techniques among patients and surgeons alike A method for preparing concentrated fibrinogen for use in autologous fibrin adhesive is described . The adhesive was used in seven patients with eight chronic leg ulcers . The ulcers were divided into two equal sections , and the adhesive was used to seal split-thickness skin grafts in one section , while no adhesive was used to seal the grafts in the other section of the ulcer . The strength of adhesion was measured 3 1/2 minutes after transplantation of a 1-cm2 test split-thickness skin graft . In the sealed grafts , the breaking strength varied from 12 to 26 gm . In the unsealed transplants , the strength was less than 5 gm . The take of the meshed split-thickness skin grafts was equal in the sealed and the unsealed areas , varying from 90 to 100 percent . Biopsies taken on day 7 showed a splitting between graft and recipient bed in half the unsealed grafts ; none of the sealed grafts showed splitting , indicating a more stable graft in the sealed areas . Biopsies taken on day 21 showed no difference between sealed and unsealed grafts OBJECTIVE To compare the tissue adhesive octylcyanoacrylate with subcuticular suture for the closure of head and neck incisions . DESIGN A prospect i ve comparison with a blinded assessment of cosmetic outcome . SUBJECTS Fifty consecutive patients undergoing head and neck procedures at two University of Ottawa teaching hospitals . METHODS Twenty-six patients underwent skin closure with monofilament suture and 24 were closed with tissue adhesive . At 4 to 6 weeks the incisions were evaluated with a vali date d wound scale . Photographs of the incisions were rated using a visual analogue scale by two facial-plastic otolaryngologists who were blinded to the method of skin closure . RESULTS The adhesive provided faster skin closure ( 29.7 seconds vs 289.0 seconds , p < .0001 ) , and there were no differences in complications between the two groups . The primary outcome measure was the cosmetic appearance of the incision at 4 to 6 weeks . Although the adhesive group scored higher on both cosmesis scales , the visual analogue scale ( octylcyanoacrylate 58.7 mm vs suture 53.2 mm ) and the wound evaluation scale ( 57 % vs 50 % optimal wound scores ) , there were no statistical or clinical ly significant differences on either scale . The two facial-plastic otolaryngologists had good intraobserver and interobserver agreement when rating the cosmetic outcomes ( 0.87 and 0.71 respectively ) . CONCLUSIONS Octylcyanoacrylate was found to be an effective method of skin closure in clean head and neck incisions . The practical advantages of tissue adhesives are review ed Two different st and ard incisions were used to compare the healing of wounds closed with normal " atraumatic " surgical technique and with a tissue adhesive . Healing was recorded by serial photography . It was found that wounds , which were not under tension postoperatively , the result ing scar was cosmetically better when tissue adhesive was used compared with conventional methods of suture BACKGROUND Surgical site infections ( SSI ) are the most common nosocomial infection in surgical patients , accounting for 38 % of all such infections , and are a significant source of postoperative morbidity result ing in increased hospital length of stay and increased cost . During 1986 - 1996 the Center for Disease Control and Prevention 's National Nosocomial Infections Surveillance system reported 15,523 SSI following 593,344 operations ( 2.6 % ) . Previous studies have documented patient characteristics associated with an increased risk of SSI , including diabetes , tobacco or steroid use , obesity , malnutrition , and perioperative blood transfusion . In this study we sought to reevaluate risk factors for SSI in a large cohort of noncardiac surgical patients . METHODS Prospect i ve data ( NSQIP ) were collected on 5031 noncardiac surgical patients at the Veteran 's Administration Maryl and Healthcare System from 1995 to 2000 . All preoperative risk factors were evaluated as independent predictors of surgical site infection . RESULTS The mean age of the study cohort was 61 plus minus 13 . SSI occurred in 162 patients , comprising 3.2 % of the study cohort . Gram-positive organisms were the most common bacterial etiology . Multiple logistic regression analysis documented that diabetes ( insulin- and non-insulin-dependent ) , low postoperative hematocrit , weight loss ( within 6 months ) , and ascites were significantly associated with increased SSI . Tobacco use , steroid use , and chronic obstructive pulmonary disease ( COPD ) were not predictors for SSI . CONCLUSION This study confirms that diabetes and malnutrition ( defined as significant weight loss 6 months prior to surgery ) are significant preoperative risk factors for SSI . Postoperative anemia is a significant risk factor for SSI . In contrast to prior analyses , this study has documented that tobacco use , steroid use , and COPD are not independent predictors of SSI . Future SSI studies should target early preoperative intervention and optimization of patients with diabetes and malnutrition BACKGROUND High-viscosity 2-octyl cyanoacrylate ( HVOCA ) is a rapidly polymerizing liquid topical adhesive indicated for epidermal approximation of superficial lacerations and surgical wounds . Use of HVOCA in repair of facial wounds after Mohs micrographic surgery ( MMS ) has not been reported . OBJECTIVE To compare aesthetic outcome of HVOCA versus sutured epidermal closure of linearly repaired facial wounds following MMS . METHODS Patients undergoing MMS for facial tumors with postoperative wounds > 3 cm appropriate for linear closure were recruited . After placement of dermal sutures , half the wound was r and omly selected for closure with HVOCA and the other half was closed with 5 - 0 polypropylene suture . RESULTS Fourteen patients ( 13 men and 1 woman ; mean age , 72±8.8 years ; range , 52–81 years ) with basal cell or squamous cell carcinoma of the face ( n=12 ) or neck ( n=2 ) were enrolled . The mean wound length was 4.9±1.9 cm ( range , 3.1–10 cm ) . No postoperative complications , including bleeding , infection , or dehiscence , occurred . Using photographs obtained 3 months postoperatively , five dermatologists ( including two Mohs surgeons ) blinded to the intervention rated cosmesis using a visual analog scale from 1 ( worst ) to 10 ( best ) . The mean ratings for HVOCA half ( 6.64±1.55 ) versus sutured half ( 6.77±1.88 ) were not significantly different ( p=.35 ) . Paired comparisons of rater preferences similarly showed no cosmetic differences . All 14 patients preferred OCA for ease of postoperative care . CONCLUSION HVOCA tissue adhesive is cosmetically equivalent to epidermal sutures in the linear repair of facial wounds following MMS . This technique represents an additional option for Mohs surgeons BACKGROUND Surgeons have become increasingly interested in replacing conventional sutures by means of adhesive bonds for the closure of skin wounds . There are several advantages to the use of adhesive bonds compared with the conventional sutures . METHODS Between January and August 2001 , all the wounds in children after groin surgery were closed with an adhesive , N-butylcyanoacrylate ( Indermil , Locite Corp , ' s-Hertogenbosch , The Netherl and s ) , or with a suture , polyglactin 5 - 0 ( Vicryl ) , intracutaneously . Fifty Inguinal wounds were treated with Indermil and 50 with Vicryl . Wounds were evaluated for hematoma , infection , dehiscence , or formation of granuloma . A scale from 1 to 10 expressed the cosmesis by patient and surgeon . RESULTS The most remarkable difference in wound healing was dehiscence of the wound in 26 % of cases in the adhesive group and no dehiscence in the suture group . The cosmesis of the wounds was marked with an 8.6 in the suture group and in the adhesive group with a 6.8 . CONCLUSIONS Wound dehiscence was seen significantly more frequent in the patients in whom the wound was closed with N-butylcyanoacrylate . The cosmesis of wounds closed with tissue glue was significantly lower then the cosmesis after suturing . Therefore , the authors advise , on the basis of this prospect i ve r and omized trial , that surgical wounds in children should be closed with a intracutaneous absorbable suture Several methods for skin closure are used , i.e. sutures , adhesive papertape and tissue adhesives . Little is known about the efficacy of these techniques in laparoscopic surgery . This study was performed to analyse the efficacy of octylcyanoacrylate , a new tissue adhesive , adhesive papertape and poliglecaprone for wound closure in laparoscopy BACKGROUND Most lacerations and surgical incisions are closed with sutures or staples . Octylcyanoacrylate tissue adhesive ( OCA ) was recently approved for use in the United States . We compared the cosmetic appearance of lacerations and incisions repaired with OCA versus st and ard wound closure methods ( SWC ) . METHODS A multicenter r and omized clinical trial including patients with simple lacerations or surgical incisions was conducted at 10 clinical sites . Patients were r and omly assigned to treatment with OCA or SWC . Follow-up was performed at 1 week and at 3 months to determine infection rates and cosmetic outcome . RESULTS Eight hundred fourteen patients with 924 wounds ( 383 traumatic lacerations , 235 excisions of skin lesions or scar revisions , 208 minimally invasive surgeries , and 98 general surgical procedures ) were enrolled . Groups were similar in baseline characteristics . Wound closure with OCA was faster than with SWC ( 2.9 vs 5.2 minutes , P < .001 ) . At 1 week infection rates were similar ( OCA , 2.1 % vs SWC , 0.7 % ; P = .09 ) and fewer OCA wounds were erythematous ( 18 % vs 36 % , P < .001 ) . There were no differences in wound dehiscence rates ( OCA , 1.6 % vs SWC , 0.9 % ; P = .35 ) . At 3 months there was no difference in the percent of wounds with optimal appearance ( OCA , 82 % vs SWC , 83 % ; P = .67 ) . CONCLUSIONS Repair of traumatic lacerations and surgical incisions with OCA is faster than with SWC , and cosmetic outcome is similar at 3 months To develop an appearance scale that will allow the objective and scientific comparison of the cosmetic results of healed lacerations , 33 photographs of healed lacerations and incisions with variable cosmetic results were shown to four plastic surgeons . These plastic surgeons were asked to independently rate the photographs on two separate occasions using two scales , a Visual Analogue Scale and a Categorical Scale . Interobserver and intraobserver agreement were determined for each scale . Comparison of the scales with each other was done to assess consistency . The Visual Analogue Scale showed good interobserver agreement with an Intraclass Correlation Coefficient of 0.75 . Intraobserver agreement was also high across the four observers with Pearson correlation coefficients ranging from 0.73 to 0.87 . The agreement of the categorical scale was also good with a kappa coefficient for interobserver agreement of 0.53 . The kappa coefficient for intraobserver agreement ranged from 0.48 to 0.72 . Because the visual analogue scale and categorical scale showed good interobserver and intraobserver agreement , both may be considered good measurement tools in the comparison of alternate methods of laceration care BACKGROUND Although upper eyelid blepharoplasty is a common procedure , subtleties in surgical technique can affect cosmetic outcomes . Suture material s commonly used include polypropylene , monofilament nylon , fast‐absorbing gut , and ethylcyanoacrylate ( ECA ) tissue adhesive . OBJECTIVE To assess upper lid blepharoplasty scars in participants whose incision had been closed with 6‐0 polypropylene sutures , 6‐0 fast‐absorbing gut sutures , or ECA . MATERIAL S AND METHODS A r and omized , split‐eyelid , single‐blind , prospect i ve study of the short‐ ( 1 month ) and intermediate‐term ( 3 months ) efficacy of polypropylene , fast‐absorbing gut , and ECA on 36 consecutive upper lid blepharoplasties . Participants and a blinded physician evaluator evaluated cosmetic outcome 1 and 3 months after the procedure . RESULTS Three subgroups tested were ECA versus fast‐absorbing gut , ECA versus polypropylene , and fast‐absorbing gut versus polypropylene . At 1 month , ECA was superior to fast‐absorbing gut ( p=.03 ) and had a marginally better outcome than polypropylene ( p=.25 ) , and polypropylene had an equivalent outcome to fast‐absorbing gut ( p=.46 ) . At 3‐month follow‐up , ECA remained superior to fast‐absorbing gut ( p=.03 ) . CONCLUSION Although sutured epidermal closure and tissue adhesive are highly efficacious for upper eyelid blepharoplasty , physicians and participants felt that cosmesis with ECA was superior to that with fast‐absorbing gut . The authors have indicated no significant interest with commercial supporters |
12,116 | 30,854,568 | CONCLUSION Denosumab can be used both as a first-line agent and an alternative to bisphosphonate in the treatment of postmenopausal osteoporosis .
There is currently insufficient data to show that denosumab is not inferior to bisphosphonates in fracture prevention | INTRODUCTION Osteoporosis is the main cause of fractures among women after menopause .
This study aim ed to evaluate the efficacy and safety of denosumab compared to bisphosphonates in treating postmenopausal osteoporosis . | Context : Denosumab 60 mg sc injection every 6 months for 36 months was well tolerated and effective in reducing the incidence of vertebral , nonvertebral , and hip fracture in predominantly Caucasian postmenopausal women with osteoporosis . Objective : The objective of this phase 3 fracture study was to examine the antifracture efficacy and safety of denosumab 60 mg in Japanese women and men with osteoporosis compared with placebo . Design and Setting : A r and omized , double-blind , placebo-controlled trial with an open-label active comparator as a referential arm was conducted . Patients : Subjects were 1262 Japanese patients with osteoporosis aged 50 years or older , who had one to four prevalent vertebral fractures . Intervention : Subjects were r and omly assigned to receive denosumab 60 mg sc every 6 months ( n = 500 ) , placebo for denosumab ( n = 511 ) , or oral alendronate 35 mg weekly ( n = 251 ) . All subjects received daily supplements of calcium and vitamin D. Main Outcome Measure : The primary endpoint was the 24-month incidence of new or worsening vertebral fracture for denosumab vs placebo . Results : Denosumab significantly reduced the risk of new or worsening vertebral fracture by 65.7 % , with incidences of 3.6 % in denosumab and 10.3 % in placebo at 24 months ( hazard ratio 0.343 ; 95 % confidence interval 0.194–0.606 , P = .0001 ) . No apparent difference in adverse events was found between denosumab and placebo during the first 24 months of the study . Conclusion : These results provide evidence of the efficacy and safety of denosumab 60 mg sc every 6 months in Japanese subjects with osteoporosis CONTEXT Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB lig and , a mediator of osteoclastogenesis and osteoclast survival . OBJECTIVE This study evaluated the ability of denosumab to increase bone mineral density ( BMD ) and decrease bone turnover markers ( BTMs ) in early and later postmenopausal women with low BMD . DESIGN AND SETTING This 2-yr r and omized , double-blind , placebo-controlled study was conducted in North America . PARTICIPANTS Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5 . INTERVENTIONS SUBJECTS were r and omly assigned to receive denosumab sc , 60 mg every 6 months , or placebo . R and omization was stratified by time since onset of menopause ( < or = 5 yr or > 5 yr ) . MAIN OUTCOME MEASURES The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months . Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography ; percent change in BMD by dual-energy x-ray absorptiometry for the total hip , one-third radius , and total body ; hip structural analysis ; percent change in BTMs ; and safety . RESULTS Denosumab significantly increased lumbar spine BMD , compared with placebo at 24 months ( 6.5 vs. -0.6 % ; P<0.0001 ) with similar results for both strata . Denosumab also produced significant increases in BMD at the total hip , one-third radius , and total body ( P < 0.0001 vs. placebo ) ; increased distal radius volumetric BMD ( P < 0.01 ) ; improved hip structural analysis parameters ; and significantly suppressed serum C-telopeptide , tartrate-resistant acid phosphatase-5b , and intact N-terminal propeptide of type 1 procollagen . The overall incidence of adverse events was similar between both study groups . CONCLUSIONS Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women CONTEXT For many patients , adhering to postmenopausal osteoporosis treatment is a challenge . Higher treatment satisfaction is associated with greater persistence with these therapies , which is associated with better outcomes . OBJECTIVE This study aim ed to evaluate the change in treatment satisfaction in postmenopausal women who were suboptimally adherent to daily or weekly oral bisphosphonates and who transitioned to denosumab vs a monthly oral bisphosphonate . DESIGN AND SETTING Pooled data of out patients from two international , multicenter , r and omized , open-label studies were analyzed . PATIENTS Postmenopausal women ( n = 1703 ) age 55 years or greater with low bone mineral density who were suboptimally adherent with prior oral bisphosphonate therapy , as assessed by the Osteoporosis-Specific Morisky Medication Adherence Scale , were included in the study . INTERVENTIONS Patients received denosumab , a fully human monoclonal antibody to receptor activator of nuclear factor-kappa B lig and , 60 mg s.c . every 6 months vs the oral bisphosphonates ib and ronate or risedronate , 150 mg once monthly for 12 months . MAIN OUTCOME MEASURES Change in treatment satisfaction scores from baseline to months 6 and 12 were measured using the Treatment Satisfaction Question naire for Medication ( TSQM ) . The TSQM is a vali date d tool that measures perception of four domains of treatment satisfaction : effectiveness , side effects , convenience , and global satisfaction . RESULTS Patients in both treatment groups showed improvement from baseline for all four TSQM domains at 6 and 12 months . However , the denosumab group had significantly ( all P < .001 ) greater improvements among all four TSQM domains at 6 and 12 months compared with the oral bisphosphonate group . CONCLUSIONS Women with low adherence to oral bisphosphonates reported greater treatment satisfaction when transitioned to denosumab vs switching to a monthly oral bisphosphonate INTRODUCTION Denosumab is a fully human monoclonal antibody that inhibits receptor activator of nuclear factor-kappa B lig and ( RANKL ) , an essential mediator of osteoclast formation , function , and survival that has been shown to decrease bone turnover and increase bone mineral density ( BMD ) in treated patients . We assessed the long-term efficacy and safety of denosumab , and the effects of discontinuing and restarting denosumab treatment in postmenopausal women with low bone mass . METHODS Postmenopausal women with a lumbar spine T-score of -1.8 to -4.0 or proximal femur T-score of -1.8 to -3.5 were r and omized to denosumab every 3 months ( Q3 M ; 6 , 14 , or 30 mg ) or every 6 months ( Q6 M ; 14 , 60 , 100 , or 210 mg ) ; placebo ; or open-label oral alendronate weekly . After 24 months , patients receiving denosumab either continued treatment at 60 mg Q6 M for an additional 24 months , discontinued therapy , or discontinued treatment for 12 months then re-initiated denosumab ( 60 mg Q6 M ) for 12 months . The placebo cohort was maintained . Alendronate-treated patients discontinued alendronate and were followed . Changes in BMD and bone turnover markers ( BTM ) as well as safety outcomes were evaluated . RESULTS Overall , 262/412 ( 64 % ) patients completed 48 months of study . Continuous , long-term denosumab treatment increased BMD at the lumbar spine ( 9.4 % to 11.8 % ) and total hip ( 4.0 % to 6.1 % ) . BTM were consistently suppressed over 48 months . Discontinuation of denosumab was associated with a BMD decrease of 6.6 % at the lumbar spine and 5.3 % at the total hip within the first 12 months of treatment discontinuation . Retreatment with denosumab increased lumbar spine BMD by 9.0 % from original baseline values . Levels of BTM increased upon discontinuation and decreased with retreatment . Adverse event rates were similar among treatment groups . CONCLUSIONS In postmenopausal women with low BMD , long-term denosumab treatment led to gains in BMD and reduction of BTM throughout the course of the study . The effects on bone turnover were fully reversible with discontinuation and restored with subsequent retreatment OBJECTIVE : To compare the efficacy and safety of denosumab to ib and ronate in postmenopausal women with low bone mineral density ( BMD ) previously treated with a bisphosphonate . METHODS : In a r and omized , open-label study , postmenopausal women received 60 mg denosumab subcutaneously every 6 months ( n=417 ) or 150 mg ib and ronate orally every month ( n=416 ) for 12 months . End points included percentage change from baseline in total hip , femoral neck , and lumbar spine BMD at month 12 and percentage change from baseline in serum C-telopeptide at months 1 and 6 in a sub study . RESULTS : At month 12 , significantly greater BMD gains from baseline were observed with denosumab compared with ib and ronate at the total hip ( 2.3 % compared with 1.1 % ) , femoral neck ( 1.7 % compared with 0.7 % ) , and lumbar spine ( 4.1 % compared with 2.0 % ; treatment difference P<.001 at all sites ) . At month 1 , median change in serum C-telopeptide from baseline was −81.1 % with denosumab and –35.0 % with ib and ronate ( P<.001 ) ; the treatment difference remained significant at month 6 ( P<.001 ) . Adverse events occurred in 245 ( 59.6 % ) denosumab-treated women and 230 ( 56.1 % ) ib and ronate-treated women ( P=.635 ) . The incidence of serious adverse events was 9.5 % for denosumab-treated women and 5.4 % for ib and ronate-treated women ( P=.046 ) . No clustering of events in any organ system accounted for the preponderance of these reports . The incidence rates of serious adverse events involving infection and malignancy were similar between treatment groups . CONCLUSION : In postmenopausal women previously treated with a bisphosphonate and low BMD , denosumab treatment result ed in greater BMD increases than ib and ronate at all measured sites . No new safety risks with denosumab treatment were identified . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00936897 . LEVEL OF EVIDENCE : BACKGROUND Receptor activator of nuclear factor-kappaB lig and ( RANKL ) is essential for osteoclast differentiation , activation , and survival . The fully human monoclonal antibody denosumab ( formerly known as AMG 162 ) binds RANKL with high affinity and specificity and inhibits RANKL action . METHODS The efficacy and safety of subcutaneously administered denosumab were evaluated over a period of 12 months in 412 postmenopausal women with low bone mineral density ( T score of -1.8 to -4.0 at the lumbar spine or -1.8 to -3.5 at the proximal femur ) . Subjects were r and omly assigned to receive denosumab either every three months ( at a dose of 6 , 14 , or 30 mg ) or every six months ( at a dose of 14 , 60 , 100 , or 210 mg ) , open-label oral alendronate once weekly ( at a dose of 70 mg ) , or placebo . The primary end point was the percentage change from baseline in bone mineral density at the lumbar spine at 12 months . Changes in bone turnover were assessed by measurement of serum and urine telopeptides and bone-specific alkaline phosphatase . RESULTS Denosumab treatment for 12 months result ed in an increase in bone mineral density at the lumbar spine of 3.0 to 6.7 percent ( as compared with an increase of 4.6 percent with alendronate and a loss of 0.8 percent with placebo ) , at the total hip of 1.9 to 3.6 percent ( as compared with an increase of 2.1 percent with alendronate and a loss of 0.6 percent with placebo ) , and at the distal third of the radius of 0.4 to 1.3 percent ( as compared with decreases of 0.5 percent with alendronate and 2.0 percent with placebo ) . Near-maximal reductions in mean levels of serum C-telopeptide from baseline were evident three days after the administration of denosumab . The duration of the suppression of bone turnover appeared to be dose-dependent . CONCLUSIONS In postmenopausal women with low bone mass , denosumab increased bone mineral density and decreased bone resorption . These preliminary data suggest that denosumab might be an effective treatment for osteoporosis . ( Clinical Trials.gov number , NCT00043186 . ) The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause . Denosumab suppresses remodeling more than alendronate , leading to greater gains in areal bone mineral density ( aBMD ) . These greater gains may reflect differing effects of each drug on bone microarchitecture and strength . In a phase 2 double-blind pilot study , 247 postmenopausal women were r and omized to denosumab ( 60 mg subcutaneous 6 monthly ) , alendronate ( 70 mg oral weekly ) , or placebo for 12 months . All received daily calcium and vitamin D. Morphologic changes were assessed using high-resolution peripheral quantitative computed tomography ( HR-pQCT ) at the distal radius and distal tibia and QCT at the distal radius . Denosumab decreased serum C-telopeptide more rapidly and markedly than alendronate . In the placebo arm , total , cortical , and trabecular BMD and cortical thickness decreased ( -2.1 % to -0.8 % ) at the distal radius after 12 months . Alendronate prevented the decline ( -0.6 % to 2.4 % , p = .051 to < .001 versus placebo ) , whereas denosumab prevented the decline or improved these variables ( 0.3 % to 3.4 % , p < .001 versus placebo ) . Changes in total and cortical BMD were greater with denosumab than with alendronate ( p < or = .024 ) . Similar changes in these parameters were observed at the tibia . The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups ( p < .001 ) . Adverse events did not differ by group . These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab Patients treated with bisphosphonates for osteoporosis may discontinue or require a switch to other therapies . Denosumab binds to RANKL and is a potent inhibitor of bone resorption that has been shown to increase bone mineral density ( BMD ) and decrease fracture risk in postmenopausal women with osteoporosis . This was a multicenter , international , r and omized , double-blind , double-dummy study in 504 postmenopausal women > or = 55 years of age with a BMD T-score of -2.0 or less and -4.0 or more who had been receiving alendronate therapy for at least 6 months . Subjects received open-label br and ed alendronate 70 mg once weekly for 1 month and then were r and omly assigned to either continued weekly alendronate therapy or subcutaneous denosumab 60 mg every 6 months and were followed for 12 months . Changes in BMD and biochemical markers of bone turnover were evaluated . In subjects transitioning to denosumab , total hip BMD increased by 1.90 % at month 12 compared with a 1.05 % increase in subjects continuing on alendronate ( p < .0001 ) . Significantly greater BMD gains with denosumab compared with alendronate also were achieved at 12 months at the lumbar spine , femoral neck , and 1/3 radius ( all p < .0125 ) . Median serum CTX levels remained near baseline in the alendronate group and were significantly decreased versus alendronate ( p < .0001 ) at all time points with denosumab . Adverse events and serious adverse events were balanced between groups . No clinical hypocalcemic adverse events were reported . Transition to denosumab produced greater increases in BMD at all measured skeletal sites and a greater reduction in bone turnover than did continued alendronate with a similar safety profile in both groups UNLABELLED Denosumab is a monoclonal antibody to RANKL . In this r and omized , placebo-controlled study of 412 postmenopausal women with low BMD , subcutaneous denosumab given every 3 or 6 mo was well tolerated , increased BMD , and decreased bone resorption markers for up to 24 mo . Continued study of denosumab is warranted in the treatment of low BMD in postmenopausal women . INTRODUCTION Denosumab is a fully human monoclonal antibody that inhibits RANKL , a key mediator of osteoclastogenesis and bone remodeling . This prespecified exploratory analysis evaluated the efficacy and safety of denosumab through 24 mo in the treatment of postmenopausal women with low BMD . MATERIAL S AND METHODS Four hundred twelve postmenopausal women with lumbar spine BMD T-scores of -1.8 to -4.0 or femoral neck/total hip T-scores of -1.8 to -3.5 were r and omly assigned to receive double-blind , subcutaneous injections of placebo ; denosumab 6 , 14 , or 30 mg every 3 mo ; denosumab 14 , 60 , 100 , or 210 mg every 6 mo ; or open-label oral alendronate 70 mg once weekly . Outcome measures included BMD at the lumbar spine , total hip , distal one-third radius , and total body ; bone turnover markers ; and safety . RESULTS Denosumab increased BMD at all measured skeletal sites and decreased concentrations of bone turnover markers compared with placebo at 24 mo . At the lumbar spine , BMD increases with denosumab ranged from 4.13 % to 8.89 % . BMD changes with denosumab 30 mg every 3 mo and > or = 60 mg every 6 mo were similar to , or in some cases greater than , with alendronate . The incidence of adverse events was similar in the placebo , denosumab , and alendronate treatment groups . Exposure-adjusted adverse events over 2 yr of treatment were similar to those reported during the first year of treatment . CONCLUSIONS In these postmenopausal women with low BMD , treatment with denosumab for 2 yr was associated with sustained increases in BMD and reductions in bone resorption markers compared with placebo Objective This study aims to evaluate patient perceptions of subcutaneous denosumab or oral alendronate in postmenopausal women with or at risk for osteoporosis and how these perceptions influence adherence . Methods Postmenopausal women with low bone mass were r and omized to denosumab 60 mg every 6 months for 1 year ( treatment period 1 [ TP1 ] ) followed by alendronate 70 mg once weekly for 1 year ( treatment period 2 [ TP2 ] ) , or vice versa . Beliefs about Medicines Question naire data were collected at baseline and at 6 , 12 , 18 , and 24 months ; a necessity-concerns differential ( NCD ) was calculated for each time point . Logistic regression analyses were performed to evaluate the influences of baseline characteristics on nonadherence . Results Participants included 250 women ( alendronate/denosumab , n = 124 ; denosumab/alendronate , n = 126 ) . During TP1 , the NCD at month 6 was higher with denosumab than with alendronate ( P = 0.0076 ) . In TP2 , the NCD was higher for women switched to denosumab than for women switched to alendronate at 6 months ( P = 0.0126 ) and 12 months ( P = 0.4605 ) . Denosumab was preferred to alendronate regardless of treatment sequence ( P < 0.0001 ) . Covariate analysis revealed that higher TP2 baseline necessity scores were associated with lower odds of nonadherence ( P = 0.0055 ) , whereas higher concerns about medication scores were associated with higher odds of nonadherence ( P = 0.0247 ) . Higher NCD scores were also associated with lower odds of nonadherence ( P = 0.0015 ) . Conclusions Participants preferred denosumab to alendronate while on treatment and had more positive perceptions of denosumab than alendronate . These perceptions were associated with better adherence Denosumab has been shown to reduce new vertebral , nonvertebral , and hip fractures in postmenopausal women with osteoporosis . In subjects who were treatment-naïve or previously treated with alendronate , denosumab was associated with greater gains in bone mineral density ( BMD ) and decreases in bone turnover markers when compared with alendronate-treated subjects . This trial was design ed to compare the efficacy and safety of denosumab with risedronate over 12 months in postmenopausal women who transitioned from daily or weekly alendronate treatment and were considered to be suboptimally adherent to therapy . In this r and omized , open-label study , postmenopausal women aged ≥55 years received denosumab 60 mg subcutaneously every 6 months or risedronate 150 mg orally every month for 12 months . Endpoints included percentage change from baseline in total hip BMD ( primary endpoint ) , femoral neck , and lumbar spine BMD at month 12 , and percentage change from baseline in sCTX-1 at months 1 and 6 . Safety was also assessed . A total of 870 subjects were r and omized ( 435 , risedronate ; 435 , denosumab ) who had a mean ( SD ) age of 67.7 ( 6.9 ) years , mean ( SD ) BMD T-scores of -1.6 ( 0.9 ) , -1.9 ( 0.7 ) , and -2.2 ( 1.2 ) at the total hip , femoral neck , and lumbar spine , respectively , and median sCTX-1 of 0.3 ng/mL at baseline . At month 12 , denosumab significantly increased BMD compared with risedronate at the total hip ( 2.0 % vs 0.5 % ) , femoral neck ( 1.4 % vs 0 % ) , and lumbar spine ( 3.4 % vs 1.1 % ; p<0.0001 at all sites ) . Denosumab significantly decreased sCTX-1 compared with risedronate at month 1 ( median change from baseline of -78 % vs -17 % ; p<0.0001 ) and month 6 ( -61 % vs -23 % ; p<0.0001 ) . Overall and serious adverse events were similar between groups . In postmenopausal women who were suboptimally adherent to alendronate therapy , transitioning to denosumab was well tolerated and more effective than risedronate in increasing BMD and reducing bone turnover Vertebral fractures and trabecular bone loss are hallmarks of osteoporosis . However , 80 % of fractures are non-vertebral and 70 % of all bone loss is cortical and is produced by intracortical remodeling . The result ing cortical porosity increases bone fragility exponentially . Denosumab , a fully human anti-RANKL antibody , reduces the rate of bone remodeling more than alendronate . The aim of this study was to quantify the effects of denosumab and alendronate on cortical and trabecular bone . Postmenopausal women , mean age 61years ( range 50 to 70 ) , were r and omized double blind to placebo ( n=82 ) , alendronate 70 mg weekly ( n=82 ) , or denosumab 60 mg every 6months ( n=83 ) for 12months . Porosity of the compact-appearing cortex ( CC ) , outer and inner cortical transitional zones ( OTZ , ITZ ) , and trabecular bone volume/total volume ( BV/TV ) of distal radius were quantified in vivo from high-resolution peripheral quantitative computed tomography scans . Denosumab reduced remodeling more rapidly and completely than alendronate , reduced porosity of the three cortical regions at 6months , more so by 12months relative to baseline and controls , and 1.5- to 2-fold more so than alendronate . The respective changes at 12months were [ mean ( 95 % CI ) ] ; CC : -1.26 % ( -1.61 , -0.91 ) versus -0.48 % ( -0.96 , 0.00 ) , p=0.012 ; OTZ : -1.97 % ( -2.37 , -1.56 ) versus -0.81 % ( -1.45 , -0.17 ) , p=0.003 ; and ITZ : -1.17 % ( -1.38 , -0.97 ) versus -0.78 % ( -1.04 , -0.52 ) , p=0.021 . Alendronate reduced porosity of the three cortical regions at 6months relative to baseline and controls but further decreased porosity of only the ITZ at 12months . By 12months , CC porosity was no different than baseline or controls , OTZ porosity was reduced only relative to baseline , not controls , while ITZ porosity was reduced relative to baseline and 6months , but not controls . Each treatment increased trabecular BV/TV volume similarly : 0.25 % ( 0.19 , 0.30 ) versus 0.19 % ( 0.13 , 0.30 ) , p=0.208 . The greater reduction in cortical porosity by denosumab may be due to greater inhibition of intracortical remodeling . Head to head studies are needed to determine whether differences in porosity result in differing fracture outcomes |
12,117 | 30,909,318 | In relation to many other outcomes , including our second primary outcome of clinical disease severity in the medium term , the quality of evidence was very low , so we were unable to determine whether CT was associated with any meaningful gains .
The quality of evidence in relation to many other outcomes at end of treatment and in the medium term was too low for us to determine whether CT was associated with any gains , but we are moderately confident that CT did not lead to any gains in mood , behavioural and psychological symptoms , or capacity to perform activities of daily living .
AUTHORS ' CONCLUSIONS Relative to a control intervention , but not to a variety of alternative treatments , CT is probably associated with small to moderate positive effects on global cognition and verbal semantic fluency at end of treatment , and these benefits appear to be maintained in the medium term . | BACKGROUND Cognitive impairment , a defining feature of dementia , plays an important role in the compromised functional independence that characterises the condition .
Cognitive training ( CT ) is an approach that uses guided practice on structured tasks with the direct aim of improving or maintaining cognitive abilities .
OBJECTIVES • To assess effects of CT on cognitive and non-cognitive outcomes for people with mild to moderate dementia and their caregivers.• To compare effects of CT with those of other non-pharmacological interventions , including cognitive stimulation or rehabilitation , for people with mild to moderate dementia and their caregivers.• To identify and explore factors related to intervention and trial design that may be associated with the efficacy of CT for people with mild to moderate dementia and their caregivers . | Background : Cognitive decline leads to disability and increased health care expenditures . Methods : Effectiveness of an intervention to stimulate multiple cognitive domains was determined using a format combining traditional and computer-based activities ( Integrated Cognitive Stimulation and Training Program ) , 45 minutes a day , 2 days a week , for 6 weeks . Nonimpaired , mildly , and moderately-impaired participants > age 65 ( n = 32 ) were r and omly allocated into a control or experimental group . Using a repeated measures design participants were tested again postintervention and at 8 weeks follow-up . Results : Statistically significant improvement on Dementia Rating Scale scores occurred for mildly and moderately impaired treatment participants ( n = 15 ) . Statistical significance was demonstrated on subscales of the WMS-III : Logical Memory I and Logical Memory II . Conclusion : Blending computer-based with traditional cognitive stimulation activities shows promise in preserving cognitive function in elders . Future studies to explore efficacy in larger , more diverse sample s are needed Background Errorless learning ( EL ) is a method for optimizing learning , which uses feed-forward instructions in order to prevent people from making mistakes during the learning process . The majority of previous studies on EL taught patients with dementia artificial tasks of little or no relevance for their daily lives . Furthermore , only a few controlled studies on EL have so far been performed and just a h and ful of studies have examined the long-term effects of EL . Tasks were not always trained in the patients ’ natural or home environment , limiting the external validity of these studies . This multicenter parallel r and omized controlled trial examines the effects of EL compared with trial and error learning ( TEL ) on the performance of activities of daily living in persons with Alzheimer ’s or mixed-type dementia living at home . Methods Patients received nine 1-hour task training sessions over eight weeks using EL or TEL . Task performance was measured using video observations at week 16 . Secondary outcome measures were task performance measured at week 26 , satisfaction with treatment , need for assistance , challenging behavior , adverse events , re source utilization and treatment costs . Results A total of 161 participants were r and omized , of whom 71 completed the EL and 74 the TEL arm at week 11 . Sixty-nine EL patients and 71 TEL patients were assessed at the 16-week follow-up ( the primary measurement endpoint ) . Intention-to-treat analysis showed a significantly improved task performance in both groups . No significant differences between the treatment groups were found for primary or secondary outcomes . Conclusions Structured relearning improved the performance of activities of daily living . Improvements were maintained for 6 months . EL had no additional effect over TEL.Trial registration German Register of Clinical Trials DRKS00003117 . Registered 31 May 2011 [ Purpose ] The purpose of this study was to investigate the effect of cognitive rehabilitation including tasks of cognitive training on performance of everyday activities in elderly people with early-stage Alzheimer ’s disease . [ Subjects and Methods ] Forty-three elderly people ( 15 men , 28 women ) with a diagnosis of Alzheimer ’s disease who had a Mini-Mental State Examination ( MMSE ) score of 18 or above were r and omly assigned to two groups : the cognitive rehabilitation group ( experimental ) and control group . This study used a r and omized controlled trial design . Cognitive rehabilitation is consisted of 8 sessions , each lasting 60 minutes ( individual 30 min , group 30 min ) . The eight weekly individual sessions of cognitive rehabilitation were performed consisting of an individualized intervention focusing on a personally meaningful goal . The eight weekly group sessions involved practicing time- and -place orientation , matching faces and names , and learning memory and sustaining attention . [ Results ] Significant improvements were observed in rating of occupation performance and satisfaction , Quality of Life in Alzheimer ’s Disease ( QOL-AD ) , and the orientation subscale of the MMSE in the experimental group , whereas participants in the control group did not show any significant difference in any tests between before and after the intervention . [ Conclusion ] Cognitive rehabilitation including tasks of cognitive training is an effective intervention for improving performance and satisfaction with respect to activities of daily living and specific cognitive functions BACKGROUND Increasing evidence demonstrates the efficacy of cognitive stimulation ( CS ) in individuals with dementia . However , conducting studies in nursing homes engenders specific challenges that have limited the data gathered on this topic so far . OBJECTIVE The aim of this r and omized controlled trial was to investigate the effects of CS on cognition , quality of life ( QoL ) , behavioral symptoms , and activities of daily life in persons with dementia living in nursing homes . We further aim ed to identify predictors of the intervention 's benefits . METHODS Seventy-one persons with mild to moderate dementia were r and omly allocated to the experimental group ( EG ; n = 36 ) that visited a CS program twice weekly for eight weeks or to the control group ( CG ; n = 35 ) that was receiving usual care . Neuropsychological tests were conducted before and after the intervention period and at six-week follow-up . RESULTS There were no significant interaction effects Time × Group for the outcome measures . However , regression analysis revealed that a low cognitive baseline level predicted cognitive improvements . Furthermore , a low baseline level of QoL predicted a QoL benefit . For both findings , depression was a significant moderator , meaning that persons with fewer depressive symptoms had a higher probability of showing improvements . CONCLUSION This study provides data on profiles of patients who are most likely to profit from CS intervention in nursing-home setting s and demonstrates that treatment of depression is of the utmost relevance for a positive outcome of CS . Living conditions will have to be considered more thoroughly in future research The purpose of this study was to examine the beneficial effects of a new cognitive intervention program design ed for the care and prevention of dementia , namely Learning Therapy . The training program used systematized basic problems in arithmetic and Japanese language as training tasks . In study 1 , 16 individuals in the experimental group and 16 in the control group were recruited from a nursing home . In both groups , all individuals were clinical ly diagnosed with senile dementia of the Alzheimer type . In study 2 , we performed a single-blind , r and omized controlled trial in our cognitive intervention program of 124 community-dwelling seniors . In both studies , the daily training program using reading and arithmetic tasks was carried out approximately 5 days a week , for 15 to 20 minutes a day in the intervention groups . Neuropsychological measures were determined simultaneously in the groups both prior to and after six months of the intervention . The results of our investigations indicate that our cognitive intervention using reading and arithmetic problems demonstrated a transfer effect and they provide convincing evidence that cognitive training maintains and improves the cognitive functions of dementia patients and healthy seniors OBJECTIVE This study evaluates the efficacy at 12 months of a computer-based cognitive training ( CBCT ) program , adjunctive to traditional cognitive training ( TCT ) , on the basis of pen- and -paper exercises . METHODS Sixty patients with multi-domain mild cognitive impairment and mild Alzheimer 's disease who were already receiving cognitive training , recruited from a day hospital , were assigned into two groups following a simple r and omization procedure ( computerized r and om numbers ) : ( i ) a group that received CBCT during 3 months and TCT ( CBCT + TCT ) , n = 37 , and ( ii ) a group that received only TCT , n = 23 . Patients were assessed at baseline and after 3 and 12 months of treatment by a neuropsychologist blinded to group assignment , with a neuropsychological battery ( primary outcomes ) and measures of decision making , memory complaints , and emotional disturbances . RESULTS With the use of repeated- measures analyses of covariance , the CBCT + TCT group showed less anxiety symptoms ( F = 5.13 , p = 0.03 , d = 1.12 ) and less disadvantageous choices ( F = 4.70 , p = 0.04 , d = 0.89 ) in decision making than the TCT group at 12 months . No significant improvement or worsening was observed in the other measures examined . However , positive effect sizes favoring the CBCT + TCT group were observed in all variables . CONCLUSIONS The addition of a CBCT program was effective in anxiety and decision making but had no significant effects on outcomes in basic cognitive functions in patients who were already receiving cognitive training , possibly due to a ceiling effect . Future studies should compare the efficacy of CBCT with TCT in naïve patients Background Interventions that improve cognitive function in Alzheimer 's disease are urgently required . Aims To assess whether a novel cognitive training paradigm based on ‘ chunking ’ improves working memory and general cognitive function , and is associated with reorganisation of functional activity in prefrontal and parietal cortices ( trial registration : IS RCT N43007027 ) . Method Thirty patients with mild Alzheimer 's disease were r and omly allocated to receive 18 sessions of 30 min of either adaptive chunking training or an active control intervention over approximately 8 weeks . Pre- and post-intervention functional magnetic resonance imaging ( fMRI ) scans were also conducted . Results Adaptive chunking training led to significant improvements in verbal working memory and untrained clinical measures of general cognitive function . Further , fMRI revealed a bilateral reduction in task-related lateral prefrontal and parietal cortex activation in the training group compared with controls . Conclusions Chunking-based cognitive training is a simple and potentially scalable intervention to improve cognitive function in early Alzheimer 's disease We developed and evaluated the effect of Multimodal Cognitive Enhancement Therapy ( MCET ) consisting of cognitive training , cognitive stimulations , reality orientation , physical therapy , reminiscence therapy , and music therapy in combination in older people with mild cognitive impairment ( MCI ) or mild dementia . This study was a multi-center , double-blind , r and omized , placebo-controlled , two-period cross-over study ( two 8-week treatment phases separated by a 4-week wash-out period ) . Sixty-four participants with MCI or dementia whose Clinical Dementia Rating was 0.5 or 1 were r and omized to the MCET group or the mock-therapy ( placebo ) group . Outcomes were measured at baseline , week 9 , and week 21 . Fifty-five patients completed the study . Mini-Mental State Examination ( effect size = 0.47 , p = 0.013 ) and Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( effect size = 0.35 , p = 0.045 ) scores were significantly improved in the MCET compared with mock-therapy group . Revised Memory and Behavior Problems Checklist frequency ( effect size = 0.38 , p = 0.046 ) and self-rated Quality of Life - Alzheimer 's Disease ( effect size = 0.39 , p = 0.047 ) scores were significantly improved in the MCET compared with mock-therapy . MCET improved cognition , behavior , and quality of life in people with MCI or mild dementia more effectively than conventional cognitive enhancing activities did BACKGROUND Cognitive Rehabilitation for Alzheimer 's disease ( AD ) is an integrative multimodal intervention . It aims to maintain autonomy and quality of life by enhancing the patients ' abilities to compensate for decreased cognitive functioning . OBJECTIVE We evaluated the feasibility of a group-based Cognitive Rehabilitation approach in mild AD dementia and assessed its effect on activities of daily living ( ADL ) . METHODS We included 16 patients with AD dementia in a controlled partial-r and omized design . We adapted the manual-guided Cognitive Rehabilitation program ( CORDIAL ) to a group setting . Over the course of three months , one group received the Cognitive Rehabilitation intervention ( n = 8) , while the other group received a st and ardized Cognitive Training as an active control condition ( n = 8) . ADL-competence was measured as primary outcome . The secondary outcome parameters included cognitive abilities related to daily living , functional cognitive state , and non-cognitive domains , e.g. , quality of life . For each scale , we assessed the interaction effect ' intervention by time ' , i.e. , from pre-to post-intervention . RESULTS We found no significant interaction effect of intervention by time on the primary outcome ADL-competence . The interaction effect was significant for quality of life ( Cohen 's d : -1.43 ) , showing an increase in the intervention group compared with the control group . CONCLUSIONS Our study demonstrates the feasibility of a group-based Cognitive Rehabilitation program for patients with mild AD dementia . The Cognitive Rehabilitation showed no significant effect on ADL , possibly reflecting a lack of transfer between the therapy setting and real life . However , the group setting enhanced communication skills and coping mechanisms . Effects on ADL may not have reached statistical significance due to a limited sample size . Furthermore , future studies might use an extended duration of the intervention and integrate caregivers to a greater extent to increase transfer to activities of daily living Background : Cognitive rehabilitation ( CR ) is a cognitive intervention for patients with Alzheimer ’s disease ( AD ) that aims to maintain everyday competences . The analysis of functional connectivity ( FC ) in resting-state functional MRI has been used to investigate the effects of cognitive interventions . Objectives : We evaluated the effect of CR on the default mode network FC in a group of patients with mild AD , compared to an active control group . Methods : We performed a three-month interventional study including 16 patients with a diagnosis of AD . The intervention group ( IG ) consisted of eight patients , performing twelve sessions of CR . The active control group ( CG ) performed a st and ardized cognitive training . We used a seed region placed in the posterior cingulate cortex ( PCC ) for FC analysis , comparing scans acquired before and after the intervention . Effects were thresholded at a significance of p < 0.001 ( uncorrected ) and a minimal cluster size of 50 voxels . Results : The interaction of group by time showed a higher increase of PCC connectivity in IG compared to CG in the bilateral cerebellar cortex . CG revealed widespread , smaller clusters of higher FC increase compared with IG . Across all participants , an increase in quality of life was associated with connectivity increase over time in the bilateral precuneus . Conclusions : CR showed an effect on the FC of the DMN in the IG . These effects need further study in larger sample s to confirm if FC analysis may suit as a surrogate marker for the effect of cognitive interventions in AD Mindfulness interventions have been beneficial for healthy adults and individuals experiencing a stressful medical or mental health diagnosis . The purpose s of the current study were to : ( a ) determine feasibility of mindfulness for older adults in long-term residential setting s , and ( b ) examine differences in outcomes between a mindfulness and cognitive activity . The current study is the first mindfulness study to include individuals in moderate and severe stages of dementia , and included 36 individuals with a range of cognitive abilities . A crossover design was used , and the intervention was feasible for continued practice by individuals with cognitive impairment . Statistically significant short-term changes in agitation , discomfort , anger , and anxiety were found . Nighttime sleep did not improve , but participants slept less during the day . Long-term changes in outcomes were not found . Mindfulness may be useful in decreasing emotional reactivity and improving well-being of older adults in long-term care . TARGETS Individuals with multiple chronic conditions , including cognitive impairment . INTERVENTION DESCRIPTION The Present in the Now ( PIN ) intervention is a mindfulness intervention with three components : attentional skill exercises , body awareness activities , and compassion meditation . MECHANISMS OF ACTION Mindfulness acts to decrease emotional reactivity through cognitive and affective mechanisms of action and neural activation of the cingulate cortex , amygdala , and hippocampus . OUTCOMES Agitation , affect , stress , sleep , discomfort , and communication of need . [ Res Gerontol Nurs . 2018 ; 11(3):137 - 150 . ] Aims : This study aim ed to investigate the effect of 6-month physical exercise with a multicomponent cognitive program ( MCP ) on the cognitive function of older adults with moderate to severe Alzheimer 's disease ( AD ) . Methods : We included 33 participants with AD in a 6-month r and omized controlled trial . The intervention group participated in physical exercise and received a MCP . The control group received only the MCP . Before and after the intervention , cognitive outcomes were assessed using the Alzheimer 's Disease Assessment Scale-Cognitive Subscale ( ADAS-cog ) , Mini-Mental State Examination , and the Clock Drawing Test . Physical performance was evaluated by exercise time , the number of pedal rotation , total load , grip strength , and the Berg Balance Scale ( BBS ) . Results : In all cognitive measures , there were no significant improvements between the two groups after 6 months in the baseline value-adjusted primary analysis . However , the ADAS-cog score was significantly lower between the two groups in secondary analysis adjusted for baseline value , age , sex , and education years . All physical outcomes were significantly higher in the intervention group except for total load compared with baseline measurements . Conclusion : This study indicates that it is possible to improve cognitive function in older adults with moderate to severe AD through 6-month physical exercise with a multicomponent cognitive intervention BACKGROUND Cognitive training ( CT ) is a non-pharmacological intervention based on a set of tasks that reflect specific cognitive functions . CT is aim ed at improving cognition in patients with cognitive impairment , though no definitive conclusions have yet been drawn on its efficacy in Alzheimer 's disease ( AD ) . OBJECTIVE To assess the effectiveness of a CT program design ed to improve cognition in AD patients . METHOD This is a r and omized , controlled , single-blind , longitudinal trial with a no-treatment control condition in mild-to-moderate AD . Treated patients received in-group CT twice a week for six months , whereas controls did not . CT consisted of tasks ranging from paper- and -pencil to verbal-learning exercises . Participants ' cognitive levels were assessed at baseline , post-intervention and 6 months later by means of a complete neuropsychological test battery . Repeated measures ANOVA was used to analyze the effect of time on the outcome measures , as well as to compare treated and untreated patients over time , with demographic data considered as covariates . RESULTS Of the 140 patients enrolled , 45 in the treated group and 85 controls concluded the study . The CT significantly improved treated subjects ' cognitive functions immediately after the CT . Six months later , some test scores remained stable when compared with those obtained at baseline . The control group performed significantly worse than the treated group at each time-point , displaying a progressive cognitive decline over time . CONCLUSION Our results suggest that CT may improve cognitive functions in patients with AD and may help to temporarily slow their cognitive decline Background Currently available pharmacological and non-pharmacological treatments have shown only modest effects in slowing the progression of dementia . Our objective was to assess the impact of a long-term non-pharmacological group intervention on cognitive function in dementia patients and on their ability to carry out activities of daily living compared to a control group receiving the usual care . Methods A r and omized , controlled , single-blind longitudinal trial was conducted with 98 patients ( follow-up : n = 61 ) with primary degenerative dementia in five nursing homes in Bavaria , Germany . The highly st and ardized intervention consisted of motor stimulation , practice in activities of daily living , and cognitive stimulation ( acronym MAKS ) . It was conducted in groups of ten patients led by two therapists for 2 hours , 6 days a week for 12 months . Control patients received treatment as usual . Cognitive function was assessed using the cognitive subscale of the Alzheimer 's Disease Assessment Scale ( ADAS-Cog ) , and the ability to carry out activities of daily living using the Erlangen Test of Activities of Daily Living ( E-ADL test ) at baseline and after 12 months . Results Of the 553 individuals screened , 119 ( 21.5 % ) were eligible and 98 ( 17.7 % ) were ultimately included in the study . At 12 months , the results of the per protocol analysis ( n = 61 ) showed that cognitive function and the ability to carry out activities of daily living had remained stable in the intervention group but had decreased in the control patients ( ADAS-Cog : adjusted mean difference : -7.7 , 95 % CI -14.0 to -1.4 , P = 0.018 , Cohen 's d = 0.45 ; E-ADL test : adjusted mean difference : 3.6 , 95 % CI 0.7 to 6.4 , P = 0.015 , Cohen 's d = 0.50 ) . The effect sizes for the intervention were greater in the subgroup of patients ( n = 50 ) with mild to moderate disease ( ADAS-Cog : Cohen 's d = 0.67 ; E-ADL test : Cohen 's d = 0.69 ) . Conclusions A highly st and ardized , non-pharmacological , multicomponent group intervention conducted in a nursing-home setting was able to postpone a decline in cognitive function in dementia patients and in their ability to carry out activities of daily living for at least 12 months . Trial Registration http://www.is rct n.com Identifier : IS RCT Background and Purpose Repetitive transcranial magnetic stimulation ( rTMS ) has been examined as a potential treatment for many neurological disorders . High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory . This study explored the effect of rTMS combined with cognitive training ( rTMS-COG ) on patients with Alzheimer 's disease ( AD ) . Methods A prospect i ve , r and omized , double-blind , placebo-controlled study was performed with 27 AD patients ( 18 and 8 in the treatment and sham groups , respectively , and 1 drop-out ) . The participants were categorized into mild [ Mini-Mental State Examination ( MMSE ) score=21 - 26 ] and moderate ( MMSE score=18 - 20 ) AD groups . The rTMS protocol s were configured for six cortical areas ( both dorsolateral prefrontal and parietal somatosensory associated cortices and Broca 's and Wernicke 's areas ; 10 Hz , 90 - 110 % intensity , and 5 days/week for 6 weeks ) . Neuropsychological assessment s were performed using the AD Assessment Scale-cognitive subscale ( ADAS-cog ) , Clinical Global Impression of Change ( CGIC ) , and MMSE before , immediately after , and 6 weeks after the end of rTMS-COG treatment . Results Data from 26 AD patients were analyzed in this study . There was no significant interactive effect of time between the groups . The ADAS-cog score in the treatment group was significantly improved compared to the sham group ( 4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment , respectively ) . The MMSE and CGIC scores were also improved in the treatment group . Based on subgroup analysis , the effect of rTMS-COG was superior for the mild group compared to the total patients , especially in the domains of memory and language . Conclusions The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors , particularly during the mild stage of AD . The effect of rTMS-COG was remarkable in the memory and language domains , which are severely affected by AD Background Hyperphagia increases eating-associated risks for people with dementia and distress for caregivers . The purpose of this study was to compare the long-term effectiveness of spaced retrieval ( SR ) training and SR training combined with Montessori activities ( SR + M ) for improving hyperphagic behaviors of special care unit residents with dementia . Methods The study enrolled patients with dementia suffering from hyperphagia resident in eight institutions and used a cluster-r and omized single-blind design , with 46 participants in the SR group , 49 in the SR + M group , and 45 participants in the control group . For these three groups , trained research assistants collected baseline data on hyperphagic behavior , pica , changes in eating habits , short meal frequency , and distress to caregivers . The SR and SR + M groups underwent memory training over a 6-week training period ( 30 sessions ) , and a generalized estimating equation was used to compare data of all the three groups of subjects obtained immediately after the training period and at follow-ups 1 month , 3 months , and 6 months later . Results Results showed that the hyperphagic and pica behaviors of both the SR and SR + M groups were significantly improved ( P<0.001 ) and that the effect lasted for 3 months after training . The improvement of fast eating was significantly superior in the SR + M group than in the SR group . The improvement in distress to caregivers in both intervention groups lasted only until the posttest . Improvement in changes in eating habits of the two groups was not significantly different from that of the control group . Conclusion SR and SR + M training programs can improve hyperphagic behavior of patients with dementia . The SR + M training program is particularly beneficial for the improvement of rapid eating . Caregivers can choose a suitable memory training program according to the eating problems of their residents Background Recent research suggests that a combination of both pharmacological and psychosocial treatments targeting cognitive functions improves cognition in patients with Alzheimer ’s disease ( AD ) . The present study evaluated the effectiveness of a 1-year cognitive training ( CT ) by comparing the cognitive performance of 16 patients with AD treated with CT and cholinesterase inhibitors ( ChEIs ) ( experimental group ) with the performance of 16 patients treated with a non-specific cognitive treatment and ChEIs ( control group ) . Methods This study was a single-blind r and omized controlled trial . The patients in the experimental group received pharmacological treatment and repeated cycles of CT for 1 year , whereas the control group received pharmacological treatment and repeated cycles of non-specific cognitive exercises . The patients in the two groups were administered a variety of neuropsychological tests measuring several cognitive functions ( i.e. memory , language , reasoning , executive function , working memory and apraxia ) , activities of daily living , and depression . Results After 1 year of training , the experimental group scored significantly higher on the Mini Mental State Examination , the Milan Overall Dementia Assessment battery and in other five neuropsychological tests , compared to the control group . Conclusions Present results suggest that repeated cycles of CT in patients with AD treated with ChEIs are associated with benefits in several areas of cognitive function This controlled r and omized single-blind study evaluated the effects of cognitive training ( CT ) , compared to active music therapy ( AMT ) and neuroeducation ( NE ) , on initiative in patients with mild to moderate Alzheimer ’s disease ( AD ) . Secondarily , we explored the effects of CT on episodic memory , mood , and social relationships . Thirty-nine AD patients were r and omly assigned to CT , AMT , or NE . Each treatment lasted 3 months . Before , at the end , and 3 months after treatment , neuropsychological tests and self-rated scales assessed initiative , episodic memory , depression , anxiety , and social relationships . At the end of the CT , initiative significantly improved , whereas , at the end of AMT and NE , it was unchanged . Episodic memory showed no changes at the end of CT or AMT and a worsening after NE . The rates of the patients with clinical ly significant improvement of initiative were greater after CT ( about 62 % ) than after AMT ( about 8 % ) or NE ( none ) . At the 3-month follow-up , initiative and episodic memory declined in all patients . Mood and social relationships improved in the three groups , with greater changes after AMT or NE . In patients with mild to moderate AD , CT can improve initiative and stabilize memory , while the non-cognitive treatments can ameliorate the psychosocial aspects . The combining of CT and non-cognitive treatments may have useful clinical implication A growing body of evidence suggests that people with Alzheimer 's Disease ( AD ) show compromised spatial abilities . In addition , there exists from the earliest stages of AD a specific impairment in “ mental frame syncing , ” which is the ability to synchronize an allocentric viewpoint-independent representation ( including object-to-object information ) with an egocentric one by computing the bearing of each relevant “ object ” in the environment in relation to the stored heading in space ( i.e. , information about our viewpoint contained in the allocentric viewpoint-dependent representation ) . The main objective of this development-of-concept trial was to evaluate the efficacy of a novel VR-based training protocol focused on the enhancement of the “ mental frame syncing ” of the different spatial representations in subjects with AD . We recruited 20 individuals with AD who were r and omly assigned to either “ VR-based training ” or “ Control Group . ” Moreover , eight cognitively healthy elderly individuals were recruited to participate in the VR-based training in order to have a different comparison group . Based on a neuropsychological assessment , our results indicated a significant improvement in long-term spatial memory after the VR-based training for patients with AD ; this means that transference of improvements from the VR-based training to more general aspects of spatial cognition was observed . Interestingly , there was also a significant effect of VR-based training on executive functioning for cognitively healthy elderly individuals . In sum , VR could be considered as an advanced embodied tool suitable for treating spatial recall impairments Several data suggest that physical activity and cognitive stimulation have a positive effect on the quality of life ( QoL ) of people with Alzheimer ’s disease ( AD ) , slowing the decline due to the disease . A pilot project was undertaken to assess the effect of cognitive stimulation , physical activity , and socialization on patients with AD and their informal caregiver ’s QoL and mood . Fourteen patients with AD were r and omly divided into active treatment group and control group . At the end of treatment , a significant improvement in apathy , anxiety , depression , and QoL in the active treatment group was found . Considering caregivers , those of the active treatment group exhibited a significant improvement in their mood and in their perception of patients ’ QoL. This study provides evidence that a combined approach based on cognitive stimulation , physical activity , and socialization is a feasible tool to improve mood and QoL in patients with AD and their caregivers Background There has been longst and ing interesting in cognitive training for older adults with cognitive impairment . In this study , we will investigate the effects of working memory training , and explore augmentation strategies that could possibly consoli date the effects in older adults with mild neurocognitive disorder . Transcranial direct current stimulation ( tDCS ) has been demonstrated to affect the neuronal excitability and reported to enhance memory performance . As tDCS may also modulate cognitive function through changes in neuroplastic response , it would be adopted as an augmentation strategy for working memory training in the present study . Methods / Design This is a 4-week intervention double-blind r and omized controlled trial ( RCT ) of tDCS . Chinese older adults ( aged 60 to 90 years ) with mild neurocognitive disorder due to Alzheimer ’s disease ( DSM-5 criteria ) would be r and omized into a 4-week intervention of either tDCS-working memory ( DCS-WM ) , tDCS-control cognitive training ( DCS-CC ) , and sham tDCS-working memory ( WM-CD ) groups . The primary outcome would be working memory test – the n-back task performance and the Chinese version of the Alzheimer ’s Disease Assessment Scale – Cognitive Subscale ( ADAS-Cog ) . Secondary outcomes would be test performance of specific cognitive domains and mood . Intention-to-treat analysis would be carried out . Changes of efficacy indicators with time and intervention would be tested with mixed effect models . Discussion This study adopts the theory of neuroplasticity to evaluate the potential cognitive benefits of non-invasive electrical brain stimulation , working memory training and dual stimulation in older adults at risk of cognitive decline . It would also examine the tolerability , program adherence and adverse effects of this novel intervention . Information would be helpful for further research of dementia prevention studies .Trial registration ChiCTR-TRC-14005036 Date of registration : 31 July 2014 Background and Purpose The objective of this study was to determine the benefits of cognitive training in patients with amnestic mild cognitive impairment ( aMCI ) and those with early Alzheimer 's disease ( AD ) . Methods Eleven patients with aMCI and nine with early AD ( stage 4 on the Global Deterioration Scale ) participated in this study . Six participants with aMCI and six with AD were allocated to the cognitive training group , while five participants with aMCI and three with AD were allocated to a wait-list control group . Multicomponent cognitive training was administered in 18 weekly , individual sessions . Outcome measures were undertaken at baseline , and at 2 weeks and 3 months of follow-up . Results In the trained MCI group , there were significant improvements in the delayed-recall scores on the Seoul Verbal Learning Test at both the 2-week and 3-month follow-ups compared with baseline ( baseline , 1.6±1.5 ; 2 weeks , 4.4±1.5 , p=0.04 ; 3 months , 4.6±2.3 , p=0.04 ) . The phonemic fluency scores ( 1.0±0.8 vs. 5.0±1.8 , p=0.07 ) and Korean Mini-Mental State Examination scores ( 18.8±0.5 vs. 23.8±2.2 , p=0.07 ) also showed a tendency toward improvement at the 2-week follow-up compared to baseline in the trained AD group . Conclusions This study provides evidence of the effectiveness of cognitive training in aMCI and early AD . The efficacy of cognitive training programs remains to be verified in studies with larger sample s and a r and omized design The efficacy of a cognitive intervention consisting of training in face-name associations , spaced retrieval , and cognitive stimulation was tested in a sample of 37 patients ( 16 men , 21 women ) with probable Alzheimer disease ( AD ) . Patients with AD were r and omly assigned to receive either the cognitive intervention or a mock ( placebo ) intervention for 5 weeks . The placebo group then crossed over to receive the intervention . During the intervention , AD patients showed significant improvement in recall of personal information , face-name recall , and performance on the Verbal Series Attention Test . Improvement did not generalize to additional neuropsychologic measures of dementia severity , verbal memory , visual memory , word generation , or motor speed , or to caregiver-assessed patient quality of life . Results suggest that although face-name training , spaced retrieval , and cognitive stimulation may produce small gains in learning personal information and on a measure of attention , improvement does not generalize to overall neuropsychologic functioning or patient quality of life Background Preliminary evidence suggests that goal -oriented cognitive rehabilitation ( CR ) may be a clinical ly effective intervention for people with early-stage Alzheimer ’s disease , vascular or mixed dementia and their carers . This study aims to establish whether CR is a clinical ly effective and cost-effective intervention for people with early-stage dementia and their carers . Methods / design In this multi-centre , single-blind r and omised controlled trial , 480 people with early-stage dementia , each with a carer , will be r and omised to receive either treatment as usual or cognitive rehabilitation ( 10 therapy sessions over 3 months , followed by 4 maintenance sessions over 6 months ) . We will compare the effectiveness of cognitive rehabilitation with that of treatment as usual with regard to improving self-reported and carer-rated goal performance in areas identified as causing concern by people with early-stage dementia ; improving quality of life , self-efficacy , mood and cognition of people with early-stage dementia ; and reducing stress levels and ameliorating quality of life for carers of participants with early-stage dementia . The incremental cost-effectiveness of goal -oriented cognitive rehabilitation compared to treatment as usual will also be examined . Discussion If the study confirms the benefits and cost-effectiveness of cognitive rehabilitation , it will be important to examine how the goal -oriented cognitive rehabilitation approach can most effectively be integrated into routine health-care provision . Our aim is to provide training and develop material s to support the implementation of this approach following trial completion . Trial registration Current Controlled Trials IS RCT This study evaluated the efficacy of two different group procedures of non-pharmacological treatment in mild-to-moderate Alzheimer 's disease ( AD ) . Thirty-two patients entered the study and were divided in groups of four subjects . We compared recreational activities ( ‘ global ’ stimulation ) with a combination of procedural memory training on activities of daily living and neuropsychological rehabilitation of ‘ residual ’ functions ( ‘ cognitive-specific ’ ) . All patients and caregivers were ensured psychological support . Both group treatments were delivered for six weeks . Multidimensional efficacy assessment of functional , behavioural and neuropsychological aspects was performed . Patients receiving ‘ global ’ stimulation showed a substantial reduction in behavioural disturbances ( Neuropsychiatric Inventory [ NPI ] : frequency p = 0.034 ; severity p = 0.012 ) ; Revised Memory Behaviour Problems Checklist ( frequency p = 0.008 ; reaction p = 0.027 ) , and better performance in the Functional Living Skills Assessment ( FLSA ) , a st and ardized direct measure of performance in everyday life ( p = 0.021 ) and Verbal Fluency for Letters ( p = 0.000 ) . Patients receiving ‘ cognitive-specific ’ treatment improved only on the scale evaluating functional competence in daily living ( Nurses ’ Observation Scale for Geriatric Patients [ NOSGER ] p = 0.018 ) . At follow-up ( six months later ) , compared with baseline , patients following the ‘ global ’ stimulation treatment showed an improvement at caregiver distress on NPI ( p = 0.04 ) . No other significant difference was detected . Our results support the contention that a ‘ global ’ treatment can lead to a significant improvement in AD patients , both for behavioural and functional aspects . The ‘ cognitive-specific ’ treatment we used in this research did not show better efficacy In a r and omised controlled trial , we investigated whether a cognitive training based on rhythm – music and music improvisation exercises had positive effects on executive functions in older participants Background / Aims : This study explores the effective outcomes of a structured cognitive stimulation treatment to improve cognition and behavioral symptoms in people with dementia ( PWDs ) , using a r and omized controlled clinical trial . Methods : Thirty PWDs were divided into three groups : experimental ( treated with cognitive stimulation ) , placebo ( treated with occupational therapy ) , and control ( continuing with the usual activities of the nursing home ) . Assessment , at baseline and after a period of 8 weeks , was performed using the Clinical Dementia Rating Scale , activities of daily living , Mini-Mental State Examination , Esame Neuropsicologico Breve 2 , Geriatric Depression Scale and Behavioral Pathology in Alzheimer 's Disease Scale . Results : Only the experimental group improved its performance in cognitive tests ( p < 0.05 ) and showed a significant decrease in behavioral symptoms ( p < 0.01 ) after the treatment . Conclusions : The results suggest that a cognitive stimulation treatment for PWDs would improve not only their cognition , but also behavioral symptoms We studied changes in apathy among 77 community-dwelling older persons with mild memory loss in a r and omized clinical trial comparing two nonpharmacological interventions over four weeks . The study used a pre-post design with r and omization by site to avoid contamination and diffusion of effect . Interventions were offered twice weekly after baseline evaluations were completed . The treatment group received classroom style mentally stimulating activities ( MSAs ) while the control group received a structured early-stage social support ( SS ) group . The results showed that the MSA group had significantly lower levels of apathy ( P < .001 ) and significantly lower symptoms of depression ( P < .001 ) . While both groups improved on quality of life , the MSA group was significantly better ( P = .02 ) than the SS group . Executive function was not significantly different for the two groups at four weeks , but general cognition improved for the MSA group and declined slightly for the SS group which produced a significant posttest difference ( P < .001 ) . Recruitment and retention of SS group members was difficult in this project , especially in senior center locations , while this was not the case for the MSA group . The examination of the data at this four-week time point shows promising results that the MSA intervention may provide a much needed method of reducing apathy and depressive symptoms , while motivating participation and increasing quality of life There is enormous interest in design ing training methods for reducing cognitive decline in healthy older adults . Because it is impaired with aging , multitasking has often been targeted and has been shown to be malleable with appropriate training . Investigating the effects of cognitive training on functional brain activation might provide critical indication regarding the mechanisms that underlie those positive effects , as well as provide models for selecting appropriate training methods . The few studies that have looked at brain correlates of cognitive training indicate a variable pattern and location of brain changes - a result that might relate to differences in training formats . The goal of this study was to measure the neural substrates as a function of whether divided attentional training programs induced the use of alternative processes or whether it relied on repeated practice . Forty-eight older adults were r and omly allocated to one of three training programs . In the SINGLE REPEATED training , participants practice d an alphanumeric equation and a visual detection task , each under focused attention . In the DIVIDED FIXED training , participants practice d combining verification and detection by divided attention , with equal attention allocated to both tasks . In the DIVIDED VARIABLE training , participants completed the task by divided attention , but were taught to vary the attentional priority allocated to each task . Brain activation was measured with fMRI pre- and post-training while completing each task individually and the two tasks combined . The three training programs result ed in markedly different brain changes . Practice on individual tasks in the SINGLE REPEATED training result ed in reduced brain activation whereas DIVIDED VARIABLE training result ed in a larger recruitment of the right superior and middle frontal gyrus , a region that has been involved in multitasking . The type of training is a critical factor in determining the pattern of brain activation OBJECTIVE : To evaluate the effects of a multidisciplinary rehabilitation program on cognition , quality of life , and neuropsychiatric symptoms in patients with mild Alzheimer 's disease . METHOD : The present study was a single-blind , controlled study that was conducted at a university-based day-hospital memory facility . The study included 25 Alzheimer 's patients and their caregivers and involved a 12-week stimulation and psychoeducational program . The comparison group consisted of 16 Alzheimer 's patients in waiting lists for future intervention . INTERVENTION : Group sessions were provided by a multiprofessional team and included memory training , computer-assisted cognitive stimulation , expressive activities ( painting , verbal expression , writing ) , physiotherapy , and physical training . Treatment was administered twice a week during 6.5-h gatherings . MEASUREMENTS : The assessment battery comprised the following tests : Mini-Mental State Examination , Short Cognitive Test , Quality of Life in Alzheimer 's disease , Neuropsychiatric Inventory , and Geriatric Depression Scale . Test scores were evaluated at baseline and the end of the study by raters who were blinded to the group assignments . RESULTS : Measurements of global cognitive function and performance on attention tasks indicated that patients in the experimental group remained stable , whereas controls displayed mild but significant worsening . The intervention was associated with reduced depression symptoms for patients and caregivers and decreased neuropsychiatric symptoms in Alzheimer 's subjects . The treatment was also beneficial for the patients ' quality of life . CONCLUSION : This multimodal rehabilitation program was associated with cognitive stability and significant improvements in the quality of life for Alzheimer 's patients . We also observed a significant decrease in depressive symptoms and caregiver burden . These results support the notion that structured nonpharmacological interventions can yield adjunct and clinical ly relevant benefits in dementia treatment OBJECTIVE The authors evaluated the efficacy of a new cognitive rehabilitation program on memory and functional performance of mildly impaired Alzheimer disease ( AD ) patients receiving a cholinesterase inhibitor . METHODS Twenty-five participants in the Cognitive Rehabilitation ( CR ) condition participated in two 45-minute sessions twice per week for 24 total sessions . CR training included face-name association tasks , object recall training , functional tasks ( e.g. , making change , paying bills ) , orientation to time and place , visuo-motor speed of processing , and the use of a memory notebook . Nineteen participants in the Mental Stimulation ( MS ) condition had equivalent therapist contact and number of sessions , which consisted of interactive computer games involving memory , concentration , and problem-solving skills . RESULTS Compared with the MS condition , participants in CR demonstrated improved performance on tasks that were similar to those used in training . Gains in recall of face-name associations , orientation , cognitive processing speed , and specific functional tasks were present post-intervention and at a 3-month follow-up . CONCLUSION A systematic program of cognitive rehabilitation can result in maintained improvement in performance on specific cognitive and functional tasks in mildly impaired AD patients Background Improving the situation in older adults with cognitive decline and evidence of cognitive rehabilitation is considered crucial in long-term care of the elderly . The objective of this study was to implement a computerized errorless learning-based memory training program ( CELP ) for persons with early Alzheimer ’s disease , and to compare the training outcomes of a CELP group with those of a therapist-led errorless learning program ( TELP ) group and a waiting-list control group . Methods A r and omized controlled trial with a single-blind research design was used in the study . Chinese patients with early Alzheimer ’s disease screened by the Clinical Dementia Rating ( score of 1 ) were recruited . The subjects were r and omly assigned to CELP ( n = 6 ) , TELP ( n = 6 ) , and waiting-list control ( n = 7 ) groups . Evaluation of subjects before and after testing , and at three-month follow-up was achieved using primary outcomes on the Chinese Mini-Mental State Examination , Chinese Dementia Rating Scale , Hong Kong List Learning Test , and the Brief Assessment of Prospect i ve Memory-Short Form . Secondary outcomes were the Modified Barthel Index , Hong Kong Lawton Instrumental Activities of Daily Living Scale , and Geriatric Depression Scale-Short Form . The data were analyzed using Friedman ’s test for time effect and the Kruskal-Wallis test for treatment effect . Results Positive treatment effects on cognition were found in two errorless learning-based memory groups ( ie , computer-assisted and therapist-led ) . Remarkable changes were shown in cognitive function for subjects receiving CELP and emotional/daily functions in those receiving TELP . Conclusion Positive changes in the cognitive function of Chinese patients with early Alzheimer ’s disease were initially found after errorless training through CELP . Further enhancement of the training program is recommended Abstract Cognitive decline and dementia represent very important public health problems that impact the ability to maintain social function and independent living . The aim of this study was to investigate the effects of a nonpharmacological intervention consisting of comprehensive cognitive training in elderly people having one of three different cognitive statuses . In all , 321 elderly people with a diagnoses of mild – moderate Alzheimer 's disease ( AD ) , with mild cognitive impairment ( MCI ) and without cognitive decline were r and omly assigned to two groups : experimental group ( EG , who underwent intervention ) and control group ( CG ) , according to a prospect i ve r and omized intervention study . In the three groups , immediately after the end of the intervention , we observed a significant effect on some cognitive and noncognitive outcomes in the EGs . At the end of the intervention , we found an intermediate intervention effect on the Alzheimer 's Disease Assessment Scale ( ADAS ) score of subjects with AD , as well as on functional status , as measured by using the Instrumental Activities of Daily Living scale . A significant intervention effect was also observed on enhancement of auditory verbal short-term memory and subjective memory complaints of subjects with MCI . The group of subjects without cognitive decline obtained a significant intervention effect on subjective complaints outcomes . The obtained results demonstrated that participation in the intervention could improve performance with respect to specific cognitive functions and psychological statuses . The role of healthy lifestyle programs , such as the use of comprehensive interventions , has been shown to be efficient for enhancing memory and other abilities in aged individuals with and without cognitive decline This r and omized study evaluated the combined effect of a cognitive-communication program plus an acetylcholinesterase inhibitor ( donepezil ; donepezil-plus-stimulation group ; n = 26 ) , as compared with donepezil alone ( donepezil-only group ; n = 28 ) in 54 patients with mild to moderate Alzheimer 's disease ( AD ; Mini-Mental Status Examination score of 12- 28 ) ranging in age from 54 to 91 years . It was hypothesized that cognitive-communication stimulation in combination with donepezil would positively affect the following : ( a ) relevance of discourse , ( b ) performance of functional abilities , ( c ) emotional symptoms , ( d ) quality of life , and ( e ) overall global function , as measured by caregiver and participant report and st and ardized measures . Cognitive-communication , neuropsychiatric , functional performance , and quality of life evaluations were conducted at baseline and Month 4 , the month after the 2-month active stimulation period . Follow-up evaluations were performed at Months 8 and 12 . The stimulation program consisted of 12 hr of intervention over an 8-week period and involved participant-led discussion s requiring homework , interactive sessions about AD , and discussion s using salient life stories . Additive effects of active stimulation with donepezil were examined in 2 ways : ( 1 ) comparing mean group performance over time and ( 2 ) evaluating change scores from baseline . A Group x Time interaction was found for the donepezil-plus-stimulation group in the emotional symptoms of apathy and irritability as compared with the donepezil-only group . Evaluation of change scores from baseline to 12 months revealed a positive effect for the donepezil-plus-stimulation group on discourse and functional abilities with a trend on apathy , irritability , and patient-reported quality of life . In sum , the research revealed benefits to the donepezil-plus-stimulation group in the areas of discourse abilities , functional abilities , emotional symptoms , and overall global performance . This study adds to growing evidence that active cognitive stimulation may slow the rate of verbal and functional decline and decrease negative emotional symptoms in AD when combined with acetylcholinesterase inhibitors , indicating a need to advance research in the area of cognitive treatments . The fact that AD is a progressive brain disease should not preclude ameliorative treatment Dementia is an increasing challenge for health care and social system in developed countries . Interventions with a cognitive focus , also using assistive technology , are leading to promising results in improving cognitive and behavior symptoms in individuals with dementia . Aim of our study was to evaluate the combined effects of the st and ard cognitive training in addition to web-based rehabilitation in dementia people living in a nursing home . We have studied twenty dementia people ( 10 females and 10 males ) with a mild to moderate cognitive decline ( MMSE 25 ± 3.4 ) associated to moderate behavioral alterations , and mainly due to vascular causes . These patients were r and omly assigned to one of two groups ( experimental or st and ard treatment — namely the control group ) . All participants in the experimental group completed the specific training , consisting of 24 sessions of web-based cognitive training , for 8 weeks , in addition to st and ard rehabilitation . Each participant was evaluated by a skilled neuropsychologist before and after each treatment . The experimental group had a statistically significant change of the Geriatric Depression Scale ( p = 0.03 ) , Constructive Apraxia ( p < 0.001 ) , Matrices Attentive ( p = 0.01 ) , and Mini Mental State Examination ( p = 0.04 ) . Web-based cognitive rehabilitation can be useful in improving cognitive performance , besides psychological well-being , in demented individuals living in home care To evaluate nonpharmacologic interventions , caregivers ( 65 women , 38 men ) and their dementia-diagnosed spouses ( patients ) were r and omized to one of four treatment programs ( cognitive stimulation , dyadic counseling , dual supportive seminar , and early-stage day care ) or to a wait-list control group . Assessment s occurred initially and at postintervention ( 3 months ) . Patients were evaluated on memory , verbal fluency , and problem-solving ability , and caregivers were assessed on marital interaction , emotional status , and physical health , along with stress , coping , and social support . Caregivers also completed a program evaluation . Repeated measures procedures showed that patients in the cognitive stimulation group demonstrated more improvement over time in cognitive outcomes , and caregivers decreased in depressive symptoms . Early-stage day-care and dual supportive seminar group caregivers reported a decrease in hostility and a decrease in use of negative coping strategies , respectively . Although qualitatively derived benefits differed across groups , similarities in program content reduced the potential for quantitative differentiation among the groups The purpose of this study was to assess the effects of semantic stimulation of Alzheimer 's patients on semantic memory comparatively to psychological support . We conducted semantic training with two target categories ( musical instruments and human actions ) , because these concepts were massively failed in previous data collected in Alzheimer 's disease . Ten patients ( 57 - 78 year old , MMSE scores from 17 to 26 ) were divided in an experimental and a control group where patients received psychological support instead of semantic cognitive training . Semantic abilities were significantly improved in patients from the experimental group , but only after semantic stimulation involving examples from musical instrument category . However , further analysis failed to show an item-specific improvement , suggesting that our results could be explained by a general increase of semantic retrieval . Results could also be explained by some motivational effect caused by more attractive material . Implication s for future research and clinical applications are discussed OBJECTIVES To test the effects of the Psychomotor Activation Programme ( PAP ) on the behaviour and cognition of demented elderly people . DESIGN R and omized controlled trial with an experimental group and a control group . Post-test after 6 months . SETTING Group care projects for demented elderly people living in 11 different homes for the elderly in The Netherl and s. PARTICIPANTS One hundred and thirty-four subjects entered the study ( 72 in the experimental group and 62 in the control group ) , 42 of whom dropped out ( 27 in the experimental group and 15 in the control group ) . MEASUREMENTS Individual behaviour and group behaviour were scored using two Dutch scales ( BIP and SIPO respectively ) developed and vali date d for use in psychogeriatric population s. Cognition was measured with the short and the long versions of the Cognitive Screening Test ( CST-14 and CST-20 ) . Disability was measured with the Barthel Index . Medicine use , falls , other accidents and life events were registered . RESULTS The PAP had a beneficial effect on cognition ( CST-14 , F = 2.63 , p < or = 0.05 , effect size 0.4 ) ( CST-20 , F = 3.77 , p < or = 0.05 , effect size 0.5 ) and increased positive group behaviour in participants with relatively mild cognitive problems ( SIPO , F = 4.46 p < or = 0.05 ) . CONCLUSIONS The PAP stabilizes cognitive performance and has some beneficial effects on behaviour . Positive findings were supported by a simultaneously conducted process evaluation BACKGROUND An active cognitive lifestyle is linked to diminished dementia risk , but the underlying mechanisms are poorly understood . Potential mechanisms include disease modification , neuroprotection , and compensation . Prospect i ve , population -based brain series provide the rare opportunity to test the plausibility of these mechanisms in humans . METHODS Participants came from the United Kingdom Medical Research Council Cognitive Function and Ageing Study , comprising 13,004 individuals aged over 65 years and followed for 14 years . In study 1 , a Cognitive Lifestyle Score ( CLS ) was computed on all Cognitive Function and Ageing Study subjects to define low , middle , and high groups . By August 2004 , 329 individuals with CLS data had come to autopsy and underwent Consortium to Establish a Registry of Alzheimer 's Disease assessment . Study 2 involved more detailed quantitative histology in the hippocampus and Brodmann area 9 in 72 clinical ly matched individuals with high and low CLS . RESULTS CLS groups did not differ on several Alzheimer disease neuropathologic measures ; however , high CLS men had less cerebrovascular disease after accounting for vascular risk factors , and women had greater brain weight . No group differences were evident in hippocampal neuronal density . In Brodmann area 9 , cognitively active individuals had significantly greater neuronal density , as well as correlated increases in cortical thickness . CONCLUSIONS An active cognitive lifestyle was associated with protection from cerebrovascular disease in men , but there was no evidence for Alzheimer disease modification or hippocampal neuroprotection . Men and women both exhibited neurotrophic changes in the prefrontal lobe linked to cognitive lifestyle , consistent with a compensatory process . Lifespan complex cognitive activity may therefore protect against dementia through multiple biological pathways Objective : To examine the efficacy of cognitive speed of processing training ( SOPT ) among individuals with Parkinson disease ( PD ) . Moderators of SOPT were also examined . Methods : Eighty-seven adults , 40 years of age or older , with a diagnosis of idiopathic PD in Hoehn & Yahr stages 1–3 and on a stable medication regimen were r and omized to either 20 hours of self-administered SOPT ( using InSight software ) or a no-contact control condition . Participants were assessed at baseline and after 3 months of training ( or an equivalent delay ) . The primary outcome measure was useful field of view test ( UFOV ) performance , and secondary outcomes included cognitive self-perceptions and depressive symptoms . Results : Results indicated that participants r and omized to SOPT experienced significantly greater improvements on UFOV performance relative to controls , Wilks λ = 0.938 , F 1,72 = 4.79 , p = 0.032 , partial η2 = 0.062 . Findings indicated no significant effect of training on secondary outcomes , Wilks λ = 0.987 , F2,70 < 1 , p = 0.637 , partial η2 = 0.013 . Conclusions : Patients with mild to moderate stage PD can self-administer SOPT and improve their cognitive speed of processing , as indexed by UFOV ( a robust predictor of driving performance in aging and PD ) . Further research should establish if persons with PD experience longitudinal benefits of such training and if improvements translate to benefits in functional activities such as driving . Classification of evidence : This study provides Class III evidence that SOPT improves UFOV performance among persons in the mild to moderate stages of PD Recent studies have shown that patients with Alzheimer 's disease ( AD ) and its possible prodromal stage mild cognitive impairment benefit from cognitive interventions . Few studies so far have used an active control condition and determined effects in different stages of disease . We evaluated a newly developed 6-month group-based multicomponent cognitive intervention in a r and omized controlled pilot study on subjects with amnestic mild cognitive impairment ( aMCI ) and mild AD patients . Forty-three subjects with aMCI and mild AD were recruited . Primary outcome measures were change in global cognitive function as determined by the Alzheimer 's Disease Assessment Scale-cognitive subscale ( ADAS-cog ) and the Mini Mental Status Examination ( MMSE ) . Secondary outcomes were specific cognitive and psychopathological ratings . Thirty-nine patients were r and omized to intervention groups ( IGs : 12 aMCI , 8 AD ) and active control groups ( CGs : 12 aMCI , 7 AD ) . At the end of the study , we found significant improvements in the IG(MCI ) compared to the CG(MCI ) in the ADAS-cog ( p = 0.02 ) and for the secondary endpoint Montgomery Asberg Depression Rating Scale ( MADRS ) ( p < 0.01 ) Effects on the MMSE score showed a non-significant trend ( p = 0.07 ) . In AD patients , we found no significant effect of intervention on the primary outcome measures . In conclusion , these results suggest that participation in a 6-month cognitive intervention can improve cognitive and non-cognitive functions in aMCI subjects . In contrast , AD patients showed no significant benefit from intervention . The findings in this small sample support the use of the intervention in larger scales studies with an extended follow-up period to determine long-term effects BACKGROUND Memory complaints and decline in cognitive function are common in the elderly . Cognitive intervention has been shown to be beneficial in Alzheimer 's disease ( AD ) . However , few community-based cognitive intervention programs are available in Hong Kong . The aim of this project is to examine and compare the feasibility , acceptability , and clinical outcome of a cognitive intervention program for older patients with mild cognitive impairment and mild dementia using telemedicine versus a conventional face-to-face method . METHODS Community-dwelling older subjects with mild dementia or mild cognitive impairments were recruited from a community center . A total of 12 sessions of assessment and cognitive intervention were conducted via videoconferencing or by face-to-face method . Assessment included : Cantonese version of Mini Mental State Examination ( C-MMSE ) , Cantonese version of Rivermead Behavioural Memory test ( C-RBMT ) and Hierarchic Dementia Scale ( HDS ) . RESULTS Twenty-two clients were recruited . There was significant and comparable cognitive improvement in clients in both treatment arms . The videoconference arm was highly accepted by the clients and the community center . Overall compliance rate of participants was above 95 % . CONCLUSIONS Telemedicine was a feasible , effective and acceptable means in providing cognitive assessment and intervention to older persons with mild cognitive deficits . Promoting such a program to other community setting s would further enhance the accessibility of dementia service to the community The main goal of this study was to evaluate the impact of a cognitive rehabilitation programme on 12 behavioural and psychological symptoms of dementia ( BPSD ) in patients with mild to moderate Alzheimer 's disease ( AD ) . This six-month single-blind block-r and omised cross-over controlled study was conducted with 15 mild to moderate AD participants and their caregivers . All participants received a four-week home-based cognitive rehabilitation programme to learn/re-learn an instrumental activity of daily living . They were assessed up until three months following the end of the intervention . The Neuropsychiatric Inventory ( NPI-12 ) was employed to evaluate patients ' BPSD at seven assessment points during the course of the study . A general linear mixed model analysis performed on the NPI data revealed that aberrant motor behaviours ( AMB ) increased significantly more in the treatment condition than in the control condition . In addition , both groups registered a significant reduction of delusional symptoms during the second half of the study . Employing a multi-symptom approach to assess participants ' BPSD , this cross-over r and omised controlled study showed that an individualised cognitive rehabilitation intervention was generally well-tolerated by mild to moderate AD patients . Future cognitive rehabilitation studies conducted with this population should pay attention to AMB symptom changes The efficacy of a memory-training program to improve word-list recall and recognition was evaluated in 34 patients with probable Alzheimer 's disease ( AD ) . The patients , who were all taking donepezil throughout the 6-week intervention , were r and omly assigned to a cognitive intervention group or a control group . The Control group received didactic presentations but no formal memory training . Patients were assessed on neuropsychological tests before the 6-week training program , immediately after the training , and 8 weeks after completion of the training . Caregivers , who were blind to group assignment , completed activities of daily living ( ADLs ) and everyday memory question naires at all three timepoints . No significant main effects of group ( training vs. control ) or time were observed on any outcome measures , nor were any significant interactions found . In terms of " process " measures during the 6-week training program , the patients demonstrated modest improvement on recall and recognition of test material presented during the training sessions . These results suggest that although modest gains in learning and memory may be evident in AD patients who are taught specific strategies , the benefits do not generalize to other measures of neuropsychological functioning after a brief intervention In an interdisciplinary project on maintaining and supporting independent living in old age , ( a ) competence training , ( b ) memory training and ( c ) psychomotor training as well as ( d ) combined competence and psychomotor training and ( e ) combined memory and psychomotor training was performed with n = 309 elderly of 75 to 89 years of age for 9 months . Regardless of treatment conditions , an age-related decline of health and subjective well-being was found 1 year after the end of the training . The specific training measures each led to highly significant specific improvements of the trained functions . A favorable influence of competence training on everyday coping and hence on active strategies for staying independent as well as of memory training on all cognitive functions and especially on memory performance was found . While global psychomotor performance was not significantly improved , effects of psychomotor training on specific functions were detected . In addition , the combined psychomotor and memory training led to an improvement of psychomotor performance and to a reduction of symptoms of dementia , even though neither psychomotor training alone nor memory training alone result ed in such effects . Neurophysiological changes leading to a provision of reserve-capacity of CNS-performance are among other effects assumed as an explanation OBJECTIVES To evaluate the effect of cognitive training on cognition and health-related quality of life ( HRQoL ) in community-dwelling persons with dementia . DESIGN Single-blind r and omized controlled trial with 3- and 9-month follow-up . SETTING Adult day care centers in Helsinki , Finl and . PARTICIPANTS Older individuals with mild to moderate dementia living at home and attending adult day care twice a week ( N = 147 ; mean age 83 , 72 % female , 63 % at mild stage of dementia ) . INTERVENTION A systematic 12-week training program focused on subskills of executive function : attention , working memory , cognitive flexibility , and planning . The intervention group ( n = 76 ) underwent cognitive training twice a week for 45 minutes , and the control group ( n = 71 ) attended day care as usual . MEASUREMENTS Primary outcomes were the Alzheimer 's Disease Assessment Scale-Cognitive subscale ( ADAS-Cog ) for global cognition and the 15-dimensional instrument ( 15D ) for HRQoL. The outcomes were measured at baseline and 3 and 9 months . RESULTS Both groups deteriorated in global cognition and HRQoL during follow-up , and there were no differences between the two groups in change on the ADAS-Cog ( P = .43 ) or 15D ( P = .61 ) over time ( adjusted for age and sex ) . At 3 months , changes were 0.8 ( 95 % confidence interval ( CI ) = -0.2 - 1.8 ) for the intervention group and 1.7 ( 95 % CI = 0.6 - 2.7 ) for the control group on the ADAS-Cog and -0.040 ( 95 % CI = -0.058 to -0.021 ) for the intervention group and -0.037 ( 95 % CI = -0.056 to -0.018 ) for the control group on the 15D . CONCLUSION Systematic cognitive training had no effect on global cognition or HRQoL in community-living persons with mild to moderate dementia Background . The growing social emergency represented by Alzheimer ’s disease ( AD ) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies . Objective . We introduced a novel nonpharmacological approach for people with AD ( PWA ) named Multidimensional Stimulation group Therapy ( MST ) to improve PWA condition in different disease domains : cognition , behavior , and motor functioning . Methods . Enrolling 60 PWA in a mild to moderate stage of the disease , we evaluated the efficacy of MST with a r and omized-controlled study . Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging ( fMRI ) data were considered as outcome measures . Results . The following significant intervention-related changes were observed : reduction in Neuropsychiatric Inventory scale score , improvement in language and memory subscales of Alzheimer ’s Disease Assessment Scale – Cognitive subscale , and increased fMRI activations in temporal brain areas , right insular cortex , and thalamus . Conclusions . Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning Awareness of difficulties may have an important impact on functioning and response to intervention in early-stage Alzheimer ’s disease ( AD ) . Clinical reports and retrospective studies suggest an association , but this has not previously been tested in a prospect i ve study . Using a new measure of awareness , the Memory Awareness Rating Scale ( MARS ) , which was design ed to take account of method ological limitations identified in a review of previous studies , the present study explored the relationship between awareness of difficulties and outcome of a cognitive rehabilitation ( CR ) intervention in 12 participants with a diagnosis of early-stage Alzheimer ’s disease . The relationship between awareness and mood , behaviour and executive function was also assessed . The results provide the first demonstration in a prospect i ve study that higher levels of awareness are related to better CR outcomes . Awareness was associated with depression and reported behaviour problems , but not with performance on tests of executive function . These results suggest that variations in level of awareness in early-stage AD are influenced by psychological factors , and that explanatory models need to take these factors into account . Awareness of difficulties may serve as a useful predictor of the likely effectiveness of CR , and this may assist clinicians in selecting appropriate interventions for individuals with early-stage AD This pilot study examined the effect of computerized neuropsychological rehabilitation ( NR ) on cognitively impaired veterans ' behavior while in treatment for polysubstance abuse . A group of 10 veterans participated in a 10-session adjunctive program of NR . This group was rated for length of stay in treatment and behavioral change and participation in treatment . Comparisons were made with a group of nine veterans who were in the st and ard substance abuse treatment with no adjunctive NR . Mild to moderate neuropsychological impairments were present in both groups in the areas of immediate and delayed memory , prospect i ve memory , problem solving , and visual scanning and tracking . Relative to controls , the group that participated in NR was found to remain in treatment significantly longer and rated as having a better overall attitude in the general treatment program . These data suggest that NR may have positive treatment implication s in patients with mild to moderate neuropsychological impairment INTRODUCTION Alzheimer 's disease ( AD ) presents with significant neuropsychological deficits . Cognitive training in AD has recently started to demonstrate its efficacy . In this study , we implemented computerized cognitive training of a large group of early-stage AD patients , to identify its effects at a neuropsychological level and to investigate whether they were stable after 6 months . METHOD Overall , 80 AD patients were r and omized in two groups . Patients in the experimental group used a structured rehabilitative software three times a week for 12 consecutive weeks aim ed at training memory , attention , executive function and language skills , whereas patients in the control group underwent a control intervention . RESULTS A Repeated Measures General Linear Model considering groups ' performance at the three assessment points ( before training , after training and at the 6-month follow-up ) showed a significant interaction effect for : digit span forward ( F(2,74 ) = 2.785 , p = 0.03 ) and backward ( F(2,74 ) = 3.183 , p = 0.02 ) , two-syllable words test ( F(2,74 ) = 3.491 , p = 0.004 ) , Rivermead Behavioural Memory Test immediate ( F(2,74 ) = 2.877 , p = 0.03 ) and delayed ( F(2,74 ) = 3.783 , p = 0.003 ) , Token test ( F(2,74 ) = 4.783 , p = 0.001 ) , and Brixton test ( F(2,74 ) = 8.783 , p < 0.001 ) . For all of them , experimental group performed better than controls . CONCLUSIONS Patients in the experimental group showed a significant improvement in various neuropsychological domains , and their achievements were stable after 6 months . This study suggests an useful computerized training in AD , and should prompt further investigations about the generalizability of patients ' acquired skills to more ecologically oriented tasks OBJECTIVES The purpose of this study was to examine the beneficial effects on cognitive function by a cognitive intervention program design ed for dementia care called Learning Therapy in Japan and SAIDO Learning in the United States ( hereinafter " SAIDO Learning , " as appropriate ) . SAIDO Learning is a working memory training program that uses systematized basic problems in arithmetic and language , including reading aloud , as well as writing . DESIGN , SETTING , PARTICIPANTS , AND INTERVENTION Twenty-three nursing home residents with dementia were assigned as an intervention group , and another 24 people with dementia at another nursing home were assigned as a control group . Both nursing homes were operated by the same organization , and residents of both nursing homes received essentially the same nursing care . Thirteen and 6 subjects of the intervention and control groups , respectively , were clinical ly diagnosed as Alzheimer disease ( AD ) . RESULTS After the 6-month intervention , the participants with AD of the intervention group showed statistically significant improvement in cognitive function , as measured by the Mini-Mental State Examination ( MMSE ) compared with the control participants . In addition , post hoc analysis revealed that the Frontal Assessment Battery at Bedside ( FAB ) scores of the intervention group tended to improve after 6-month intervention . Based on MDS scores , improvements in total mood severity scores also were observed , but only in the intervention group of the participants with AD . CONCLUSION These results suggest that SAIDO Learning is an effective cognitive intervention and is useful for dementia care . An additional outcome of this intervention , which has not yet been evaluated in detail , appears to be that it promotes greater positive engagement of a diversity of nursing home staff in the residents ' individual progress and care needs Objective : The purpose of this study was to analyze the effect of a neuropsychological rehabilitation ( NR ) program on patients with Alzheimer ’s disease ( AD ) . Methods : The sample was composed of 16 elderly out patients who participated in an open trial with rivastigmine ( 6 to 12 mg/day ) for 4 months and were r and omized to 3 different groups : 1 . group NR ( N = 5 ) , 2 . individualized NR ( N = 6 ) and 3 . NR at home under supervision of a relative or caregiver ( N = 5 ) . All 3 groups fulfilled the same NR protocol consisting of a once a week session . Just before and after the 22 week period of rehabilitation , all patients were evaluated using psychiatric and functional scales , and neuropsychological tests by interviewers that did not participate in the cognitive training . Results : The intervention did not produce any statistically significant change , but small gains were observed on some cognition tests , activities of daily living ( ADL ) , and psychiatric symptoms in groups 1 and 2 . Conclusion : Group NR is recommended for reducing psychiatric symptoms , and individualized NR for improving ADL . NR at home either has no associated benefits , or the training sessions were not appropriately conducted by the caregiver . However , additional research with larger sample s is necessary to confirm these observations A cognitive remediation intervention was tested for its effect on functional outcomes of older care recipients with the diagnosis of dementia of the Alzbeimer 's type . The 78 community-dwelling care recipients were assessed on cognitive and behavioral functioning and r and omly assigned to one of three conditions . Care recipients were expected to benefit most from active cognitive stimulation training as compared to placebo ( passive ) activity or wait-list control conditions . Following each weekly instruction session , the intervention was executed in the home by the family caregiver . Care recipients in the experimental group improved in cognitive and behavioral performance with treatment , but returned to former level of functioning by the 9th month . In contrast , the control group declined , while the placebo group remained static on these variables . These findings support the viability of remediation interventions in dementia despite the trajectory of cognitive decline This study investigated the effect of cognitive training aim ed at improving shifting ability on Parkinson 's disease ( PD ) patients ' performance of prospect i ve memory ( PM ) tasks . Using a double-blind protocol , 17 PD patients were r and omly assigned to two experimental arms . In the first arm ( n=9 ) shifting training was administered , and in the second ( placebo ) arm ( n=8 ) , language and respiratory exercises . Both treatments consisted of 12 sessions executed over 4 weeks . PM and shifting measures ( i.e. , Trail Making Test and Alternate Fluency Test ) were administered at T0 ( before treatment ) and T1 ( immediately after treatment ) . A mixed analysis of variance was applied to the data . To evaluate the effects of treatment , the key effect was the interaction between Group ( experimental vs. placebo ) and Time of Assessment ( T0 vs. T1 ) . This interaction was significant for the accuracy indices of the PM procedure ( p<.05 ) and for the performance parameters of the shifting tasks ( p ≤.05 ) . Tukey 's HSD tests showed that in all cases passing from T0 to T1 performance significantly improved in the experimental group ( in all cases p ≤.02 ) but remained unchanged in the placebo group ( all p consistently>.10 ) . The performance change passing from T0 to T1 on the Alternate Fluency test and the PM procedure was significantly correlated ( p<.05 ) . Results show that the cognitive training significantly improved PD patients ' event-based PM performance and suggest that their poor PM functioning might be related to reduced shifting abilities Called dotage in Korea , dementia is primarily characterized by cognitive impairments . Secondary manifestations include mental-emotional problems , including depression . This study was design ed to examine the effects of an integrated dementia intervention for Korean older adults . The intervention is composed of cognitive stimulation training , exercise , music , art , and horticultural therapy . Participants included 38 older adults with mild dementia . Twenty were assigned to the experimental group and 18 to the control group . Participants in the experimental group attended 18 program sessions . Significant differences were found postintervention between the two groups in measures of cognitive function , depression levels , and mental-emotional health . The findings indicate that this integrated dementia intervention can be applied to help older adults with mild dementia Sundowning syndrome ( SDS ) in patients with Alzheimer 's disease ( AD ) is characterized by the intensification of behavioral disorders at sunset . Despite SDS etiology being unclear , a strong relationship between high cortisol levels and SDS has been reported . Aerobic exercise ( AE ) and cognitive training ( CT ) can reduce cortisol levels . However , whether SDS would benefit from AE and CT is still unknown . Therefore , the aim of this study was to investigate whether AE and CT treatments are effective in reducing SDS via downregulation of cortisol levels . The possible additive effects of combined AE+CT were also assessed . Eighty AD patients were r and omly assigned to AE ( n = 20 ) , CT ( n = 20 ) , AE+CT ( n = 20 ) , and st and ard therapy ( no treatment , NT ; n = 20 ) . Treatments were administered for 3 months , 5 days/week , 1 hour before sunset . Before and after treatments , salivary cortisol levels were sample d at 7 , 11 , 15 , at sunset , and 20 ( time of day ) . Blind assessment of behavioral disorders ( neuropsychiatric inventory , NPI ) and agitation ( agitated behavior scale , ABS ) were also performed . After interventions , cortisol levels were reduced in AE and AE+CT by ∼26 % . In the same groups , NPI and ABS decreased by ∼50 % . By contrast , cortisol and behavioral disorders were similar to baseline in CT and NT . Changes in NPI and ABS were significantly correlated with the reduction in cortisol levels . AE or AE+CT effects on SDS and cortisol levels and the lack of effect of CT alone indicate the effectiveness of an exercise-based treatment on SDS , suggesting a possible hypothalamic-pituitary-adrenal axis dysregulation underpinning SDS Background : The Sound Training for Attention and Memory in Dementia ( STAM-Dem ) is a manualized music-based protocol design ed to be used in the rehabilitation of cognitive functions in elderly patients with dementia ( PWD ) . Method : This was a multicenter , single-blind , r and omized , and controlled trial that involved 51 PWD . The objective was to test the STAM-Dem efficacy . Patients in the experimental group followed the STAM-Dem for 2 weekly sessions of 45 minutes for 12 weeks ( in addition to st and ard care ) . Those in the control group continued with the normal “ st and ard care ” provided . Results : In the experimental group , the instruments immediate prose memory test ( MPI ) , deferred prose memory test ( MPD ) , attentional matrices , activities of daily living , Music Therapy Activity Scale ( SVAM ) and Geriatric Music Therapy Profile ( GMP ) increase significantly from pre to post-test ( P < .05 ) . Conclusion : The protocol is feasible and data suggest that there was an effect on attentino ( matrices ) and prose memory skills ( MPI and MPD ) . The effect size reveals a general improvement in the results of the experimental group Accurate clinical staging of dementia in older subjects has not previously been achieved despite the use of such methods as psychometric testing , behavioural rating , and various combinations of simpler psychometric and behavioural evaluations . The Clinical Dementia Rating ( CRD ) , a global rating device , was developed for a prospect i ve study of mild senile dementia -- Alzheimer type ( SDAT ) . Reliability , validity , and correlational data are discussed . The CRD was found to distinguish unambiguously among older subjects with a wide range of cognitive function , from healthy to severely impaired Background . Memory decline is a prevalent aspect of aging but may also be the first sign of cognitive pathology . Virtual reality ( VR ) using immersion and interaction may provide new approaches to the treatment of memory deficits in elderly individuals . Objective . The authors implemented a VR training intervention to try to lessen cognitive decline and improve memory functions . Methods . The authors r and omly assigned 36 elderly residents of a rest care facility ( median age 80 years ) who were impaired on the Verbal Story Recall Test either to the experimental group ( EG ) or the control group ( CG ) . The EG underwent 6 months of VR memory training ( VRMT ) that involved auditory stimulation and VR experiences in path finding . The initial training phase lasted 3 months ( 3 auditory and 3 VR sessions every 2 weeks ) , and there was a booster training phase during the following 3 months ( 1 auditory and 1 VR session per week ) . The CG underwent equivalent face-to-face training sessions using music therapy . Both groups participated in social and creative and assisted-mobility activities . Neuropsychological and functional evaluations were performed at baseline , after the initial training phase , and after the booster training phase . Results .The EG showed significant improvements in memory tests , especially in long-term recall with an effect size of 0.7 and in several other aspects of cognition . In contrast , the CG showed progressive decline . Conclusions . The authors suggest that VRMT may improve memory function in elderly adults by enhancing focused attention Forty patients with probable Alzheimer 's disease ( AD ) were selected from a pool of 80 patients and assigned to 4 groups . Each received either social support , cognitive training only , or cognitive training in combination with pyritinol or phosphatidylserine . Treatment duration was 6 months . Before and after treatment the patients underwent neuropsychological testing as well as measurement of the regional cerebral metabolic rate for glucose using positron emission tomography ( PET ) and 2[18F]-fluoro-2-deoxy-D-glucose ( FDG ) . Before treatment , the groups were comparable in respect to resting and activated glucose pattern achieved by a visual recognition task . They did not differ in scores of a neuropsychological test battery . After the treatment period the group with cognitive training + phosphatidylserine showed a significant glucose enhancement during the stimulation tasks in various brain regions , and an improvement in cognitive functioning compared to the other groups . The group with cognitive training + pyritinol had better stimulation effect as that of the social support group indicating that a combination of cognitive training + pharmacological intervention was superior than that of cognitive training alone Objective : To evaluate the efficacy of a cognitive-motor program in patients with early Alzheimer disease ( AD ) who are treated with a cholinesterase inhibitor ( ChEI ) . Methods : Patients with mild cognitive impairment ( MCI ) ( 12 ) , mild AD ( 48 ) , and moderate AD ( 24 ) ( Global Deterioration Scale stages 3 , 4 , and 5 ) were r and omized to receive psychosocial support plus cognitive-motor intervention ( experimental group ) or psychosocial support alone ( control group ) . Cognitive-motor intervention ( CMI ) consisted of a 1-year structured program of 103 sessions of cognitive exercises , plus social and psychomotor activities . The primary efficacy measure was the cognitive subscale of the AD Assessment Scale ( ADAS-cog ) . Secondary efficacy measures were the Mini-Mental State Examination , the Functional Activities Question naire , and the Geriatric Depression Scale . Evaluations were conducted at 1 , 3 , 6 , and 12 months by blinded evaluators . Results : Patients in the CMI group maintained cognitive status at month 6 , whereas patients in the control group had significantly declined at that time . Cognitive response was higher in the patients with fewer years of formal education . In addition , more patients in the experimental group maintained or improved their affective status at month 12 ( experimental group , 75 % ; control group , 47 % ; p = 0.017 ) . Conclusions : A long-term CMI in ChEI-treated early Alzheimer disease patients produced additional mood and cognitive benefits Objectives : Our purpose was to evaluate the adequacy of a stress adaptation framework for guiding intervention research on caregivers and patients coping with Alzheimer ’s disease , and to test the effect of a cognitive stimulation intervention as an interactive outcome . Methods : Using a repeated measures design , 87 caregiverpatient dyads were r and omized to one of three conditions : active cognitive stimulation , passive stimulation , or control . Assessment s occurred at preintervention , postintervention ( 3 months ) , and 9 months . Results : The LISREL model was entirely satisfactory by the chi-square goodness-of-fit criteria . However , the coefficients associated with the paths between the mediating concepts and the dyadic interaction differed significantly at 3 months and 9 months . The intervention group caregivers were shown to be more satisfied with their interaction with the impaired member . Discussion : The improvement in caregiver satisfactionwas attributed to an attenuation of the behavioral stressor effects through increased use of a problem-focused coping strategy , namely , positive re appraisal of the stressful situation Cognitive research on the plasticity of fluid intelligence has demonstrated that older adults benefit markedly from guided practice in cognitive skills and problem-solving strategies . We examined to what degree older adults are capable by themselves of achieving similar practice gains , focusing on the fluid ability of figural relations . A sample of 72 healthy older adults was assigned r and omly to three conditions : control , tutor-guided training , self-guided training . Training time and training material s were held constant for the two training conditions . Posttraining performances were analyzed using a transfer of training paradigm in terms of three indicators : correct responses , accuracy , and level of item difficulty . The training programs were effective and produced a significant but narrow b and of within-ability transfer . However , there was no difference between the two training groups . Older adults were shown to be capable of producing gains by themselves that were comparable to those obtained following tutor-guided training in the nature of test-relevant cognitive skills Unawareness of deficit has been shown to affect the outcome of targeted cognitive intervention programmes applied to patients with Alzheimer ’ disease ( AD ) , but the effects on multimodal therapeutic approaches have not yet been explored . This research investigated the efficacy of the Multi-Intervention Programme ( MIP ) approach on improving cognitive , functional , affective , and behavioural symptoms in people with mild AD . In addition , we examined whether the presence of unawareness influences the MIP outcomes . Sixty-one mild stage AD patients were r and omly assigned to either an experimental group which carried out an MIP individually ( 48 sessions , 16 weeks duration ) , combining diverse cognitive tasks , training in daily life and recreational activities , or a waiting list group which did not receive any treatment for the same time period . The efficacy of MIP ( vs. waiting list ) was tested using various st and ardised neuropsychological , functional , and behavioural outcome measures . Planned analyses were carried out to determine the effect of unawareness versus awareness on such outcomes . The results showed that patients overall benefited from the MIP in terms of both cognitive and non-cognitive symptoms . AD patients with awareness of deficits showed positive effects on all outcome measures in comparison with the waiting list group , while AD patients with unawareness showed improvements in non-cognitive symptoms only . In conclusion , the presence of unawareness reduces the cognitive and functional effects of MIP in patients with mild AD BACKGROUND Although non-drug interventions are widely used in patients with Alzheimer 's disease , few large scale r and omized trials involving a long-term intervention and several cognitive-oriented approaches have been carried out . ETNA3 trial compares the effect of cognitive training , reminiscence therapy , and an individualized cognitive rehabilitation program in Alzheimer 's disease to usual care . METHODS This is a multicenter ( 40 French clinical sites ) r and omized , parallel-group trial , with a two-year follow-up comparing groups receiving st and ardized programs of cognitive training ( group sessions ) , reminiscence therapy ( group sessions ) , individualized cognitive rehabilitation program ( individual sessions ) , and usual care ( reference group ) . Six hundred fifty-three out patients with Alzheimer 's disease were recruited . The primary efficacy outcome was the rate of survival without moderately severe to severe dementia at two years . Secondary outcomes were cognitive impairment , functional disability , behavioral disturbance , apathy , quality of life , depression , caregiver 's burden , and re source utilization . RESULTS No impact on the primary efficacy measure was evidence d. For the two group interventions ( i.e. cognitive training and reminiscence ) , none of the secondary outcomes differed from usual care . The larger effect was seen with individualized cognitive rehabilitation in which significantly lower functional disability and a six-month delay in institutionalization at two years were evidence d. CONCLUSIONS These findings challenge current management practice s of Alzheimer 's patients . While cognitive-oriented group therapies have gained popularity , this trial does not show improvement for the patients . The individualized cognitive rehabilitation intervention provided clinical ly significant results . Individual interventions should be considered to delay institutionalization in Alzheimer 's disease Theories supporting the existence of a use-dependent neuroplasticity in the older brain were used to guide this pilot study . A repeated- measures r and omized design was used to test the effectiveness of a multimodal ( Taiji exercises , cognitive-behavioral therapies , support group ) intervention on cognitive functioning , physical functioning , and behavioral outcomes in persons with dementia . The treatment group ( n = 24 persons with dementia ) participated in a 40-week intervention , with outcomes assessed at 20 and 40 weeks to assess optimal treatment length . Control group subjects ( n = 19 persons with dementia ) received attention-control educational programs . At 20 weeks , differences between groups were found for mental ability and self-esteem , with gains in balance being evident . Also , stability in depression and physical health were evident at 20 and 40 weeks for treatment group subjects . Continued improvement in outcomes was not observed at 40 weeks . However , findings support further testing of the intervention along with potential for achieving positive outcomes in early-stage dementia Although some studies point to cognitive stimulation as a beneficial therapy for older adults with cognitive impairments , this area of research and practice is still lacking dissemination and is underrepresented in many countries . Moreover , the comparative effects of different intervention duration s remain to be established and , besides cognitive effects , pragmatic parameters , such as cost-effectiveness and experiential relevance to participants , are seldom explored . In this work , we present a r and omized controlled wait-list trial evaluating 2 different intervention duration s ( st and ard = 17 vs brief = 11 sessions ) of a cognitive stimulation program developed for older adults with cognitive impairments with or without dementia . 20 participants were r and omly assigned to the st and ard duration intervention program ( 17 sessions , 1.5 months ) or to a wait-list group . At postintervention of the st and ard intervention group , the wait-list group crossed over to receive the brief intervention program ( 11 sessions , 1 month ) . Changes in neuropsychological , functionality , quality of life , and caregiver outcomes were evaluated . Experience during intervention and costs and feasibility were also evaluated . The current cognitive stimulation programs ( ie , st and ard and brief ) showed high values of experiential relevance for both intervention duration s. High adherence , completion rates , and reasonable costs were found for both formats . Further studies are needed to definitively establish the potential efficacy , optimal duration , cost-effectiveness , and experiential relevance for participants of cognitive intervention approaches Background . Episodic memory and semantic abilities deteriorate early in Alzheimer disease ( AD ) . Since the cognitive system includes interconnected and reciprocally influenced neuronal networks , the authors hypothesized that stimulation of lexical – semantic abilities may benefit semantically structured episodic memory . Objective . To investigate the effects of lexical – semantic stimulation ( LSS ) on verbal communication and episodic memory in early AD . Methods . Forty AD participants were r and omized to LSS or unstructured cognitive stimulation ( UCS ) as control condition . Treatments lasted 3 months , 2 sections a week . The primary outcome measures were the Mini-Mental State Examination ( MMSE ) , Boston Naming Test ( BNT ) , Verbal Naming Test ( VNT ) , Phonemic and Semantic Fluency , Story Recall , and Rey Auditory Verbal Learning ( RAVL ) . Secondary outcome measures were neuropsychological tests assessing cognitive functions not stimulated by the intervention , such as attention , executive functions , and visual – spatial abilities , and the instrumental activities of daily living scale . A 6-month follow-up assessment was administered to the LSS group . Results . LSS treatment yielded significant improvements of the MMSE , BNT , VNT , Brief Story Recall , and RAVL delayed recall mean scores . Among secondary outcome measures , only working memory and the speed of a task assessing executive functions ( Stroop test ) improved after LSS . Unstructured cognitive stimulation intervention did not improve any cognitive domain . Six months after LSS discontinuation , the MMSE mean score remains significantly higher than the baseline value . Conclusion . LSS treatment may improve episodic memory in AD patients and may be regarded as a clinical option to counteract the cognitive decline typical of the disease BACKGROUND Given the increasing prevalence of dementia , any intervention that can effectively slow the deterioration of cognitive function is of great importance . OBJECTIVE This study investigated the efficacy of a human-computer interaction-based comprehensive cognitive training program in cognitively impaired elderly individuals living in a nursing home . METHODS All subjects , who were aged ≥70 years and had cognitive impairment , were r and omly allocated to an intervention group ( n = 19 ) or a control group ( n = 14 ) . The intervention group received human-computer interaction-based comprehensive cognitive training for 24 weeks . Neuropsychological examinations were conducted before and after this period . The intervention group was subdivided into two groups according to the scores of global cortical atrophy ( GCA ) to evaluate the impact of training effectiveness on GCA . RESULTS After 24 weeks , neither group showed a significant change compared with baseline cognitive examinations . However , there was a tendency for greater improvement in memory , language , and visuospatial abilities for the intervention group as compared with controls . Patients with mild cognitive impairment showed improvements in language and visuospatial capacity , while patients with dementia showed improvements in attention/orientation , memory , language , and fluency . However , none of these findings were statistically significant . The results for the intervention subgroups showed that visuospatial ability improvement was significantly greater among those with a global cortical atrophy score of ≤15 ( p < 0.05 ) . CONCLUSION Human-computer interaction-based comprehensive training may improve cognitive functions among cognitively impaired elderly individuals . The training effect was most prominent among those with milder cerebral atrophy BACKGROUND The Canary Isl and s longitudinal study on non-pharmacological treatments showed the overall effectiveness of mindfulness in Alzheimer 's disease ( AD ) . However , no specific data on the maintenance of cognitive capacities were presented . OBJECTIVE To determine whether the practice of mindfulness modifies the course of cognitive impairment in AD . METHODS DESIGN Longitudinal , non-inferiority and equivalence , r and omized clinical trial , repeated- measures design , with three experimental groups and one control group . PARTICIPANTS Patients with AD who voluntarily attended the Lidia García Foundation ( n = 502 ) . Only those who were treated with donepezil and MMSE ≥18 were included ( n = 120 ) . INTERVENTION Over a two-year period , each group carried out three weekly sessions of stimulation based on mindfulness , cognitive stimulation therapy , and progressive muscle relaxation . MEASURES Cognitive assessment CAMDEX-R ( MMSE and CAMCOG ) . STATISTICAL ANALYSIS Repeated- measures ANOVA ( p < 0.05 ) and the effect size Cohen 's d were performed . RESULTS The mindfulness group showed significant scores compared with the control and muscle relaxation groups ( p < 0.05 ) , while mindfulness and cognitive stimulation therapy were equivalent ( p≥0.05 ) . Group cognitive stimulation evolved better than the control ( p < 0.05 ) group but not better than the muscle relaxation group ( p≥0.05 ) . The effect size compared over two years was large for the mindfulness group ( p≥0.80 ) , moderate for the relaxation group ( p≥0.50 ) , and low for the cognitive stimulation group ( p≥0.20 ) . CONCLUSION The practice of mindfulness maintained cognitive function over a period of two years . This longitudinal study suggests that mindfulness can be used as a non-pharmacological treatment to slow cognitive impairment in AD BACKGROUND Computerized Cognitive Training ( CCT ) has been shown to improve cognitive function in older adults with mild cognitive impairment ( MCI ) or mood-related neuropsychiatric symptoms ( MrNPS ) , but many questions remain unresolved . OBJECTIVE To evaluate the extent to which CCT benefits older adults with both MCI and MrNPS , and its effects on meta-cognitive and non-cognitive outcomes , as well as establish whether adapting difficulty levels and tailoring to individuals ' profile is superior to generic training . METHODS Older adults with MCI ( n = 9 ) , MrNPS ( n = 11 ) , or both ( MCI+ , n = 25 ) were r and omized into a home-based individually-tailored and adaptive CCT ( n = 21 ) or an active control condition ( AC ; n = 23 ) in a double-blind design . Interventions lasted 8 - 12 weeks and outcomes were assessed after the intervention , and at a 3-month follow-up . RESULTS Participants in both conditions reported greater satisfaction with their everyday memory following intervention and at follow-up . However , participants in the CCT condition showed greater improvement on composite measures of memory , learning , and global cognition at follow-up . Participants with MrNPS in the CCT condition were also found to have improved mood at 3-month follow-up and reported using fewer memory strategies at the post-intervention and follow-up assessment s. There was no evidence that participants with MCI+ were disadvantaged relative to the other diagnostic conditions . Finally , informant-rated caregiver burden declined at follow-up assessment in the CCT condition relative to the AC condition . CONCLUSIONS Home-based CCT with adaptive difficulty and personal tailoring appears superior to more generic CCT in relation to both cognitive and non-cognitive outcomes . Mechanisms of treatment effect and future directions are discussed This pilot study examines whether learning without errors is advantageous compared to trial- and -error learning in people with dementia using a procedural task and a r and omized case-control design . A sample of 60 people was recruited , consisting of 20 patients with severe dementia , 20 patients with mild-to-moderate dementia and 20 participants without dementia . The participants had to acquire a novel procedural problem-solving task with the help of cues ( errorless learning ) or with cues only given in case an error was made ( trial- and -error learning ) . The number of steps completed without assistance immediately after errorless or trial- and -error learning and after a delay of 1 - 3 days was recorded . Overall performance was better after errorless learning compared to trial- and -error learning ( p=0.012 ) , with effect sizes being largest in the mild-to-moderate dementia group after delayed testing ( d=1.61 ) . The effects of errorless learning were larger after delayed testing . We conclude that errorless learning of a procedural task results in a better performance than learning with errors . This study is the first to use a controlled group design to show such a benefit in patients with dementia . These findings can be extended to the acquisition of tasks that are relevant for everyday-life functioning , having important implication s for dementia care Background : Many studies have suggested that cognitive training can result in cognitive gains in healthy older adults . We investigated whether personalized computerized cognitive training provides greater benefits than those obtained by playing conventional computer games . Methods : This was a r and omized double-blind interventional study . Self-referred healthy older adults ( n = 155 , 68 ± 7 years old ) were assigned to either a personalized , computerized cognitive training or to a computer games group . Cognitive performance was assessed at baseline and after 3 months by a neuropsychological assessment battery . Differences in cognitive performance scores between and within groups were evaluated using mixed effects models in 2 approaches : adherence only ( AO ; n = 121 ) and intention to treat ( ITT ; n = 155 ) . Results : Both groups improved in cognitive performance . The improvement in the personalized cognitive training group was significant ( p < 0.03 , AO and ITT approaches ) in all 8 cognitive domains . However , in the computer games group it was significant ( p < 0.05 ) in only 4 ( AO ) or 6 domains ( ITT ) . In the AO analysis , personalized cognitive training was significantly more effective than playing games in improving visuospatial working memory ( p = 0.0001 ) , visuospatial learning ( p = 0.0012 ) and focused attention ( p = 0.0019 ) . Conclusions : Personalized , computerized cognitive training appears to be more effective than computer games in improving cognitive performance in healthy older adults . Further studies are needed to evaluate the ecological validity of these findings |
12,118 | 31,666,272 | We found evidence that this group of affected trial reports distorted the evidence base .
Correction of these distortions is slow , uncoordinated and inconsistent . | OBJECTIVE Analyses of the impact of a body of clinical trial reports subject to research misconduct have been few .
Our objective was to examine the impact on clinical ly relevant research of a group of research ers ' trial reports ( ' affected trial reports ' ) affected by research misconduct , and whether identification of misconduct invoked a re appraisal . | OBJECTIVES A high prevalence of hip and other fractures in elderly patients with Parkinson ’s disease has been linked to reduced bone mass arising from a defect of renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) . Treatment with 1α-hydroxyvitamin D3 ( 1α(OH)D3 ; an active form of vitamin D ) was evaluated for maintaining bone mass and reducing the incidence of hip and other non-vertebral fractures in patients with Parkinson ’s disease . METHODS In a double blind , r and omised trial , 86 elderly patients with Parkinson ’s disease ( mean Hoehn and Yahr stage , 3 ; mean age 70.6 years ) were r and omised to receive either 1 μg 1α(OH)D3 daily ( treatment group , n=43 ) or a placebo ( n=43 ) for 18 months . Bone mineral densities in the second metacarpals were determined by computed radiographic densitometry . Serum bone turnover indices were measured serially , and incidence of non-vertebral fractures was recorded . RESULTS Bone mineral densities decreased 1.2 % in the treatment group compared with 6.7 % in the placebo group during 18 months ( p<0.0001 ) . At baseline in both groups , the serum concentration of 1 , 25-[OH]2D was reduced . Parathyroid hormone was abnormally increased in 15 patients ( 17 % ) and correlated negatively with serum 25-hydroxyvitamin D , indicating compensatory hyperparathyroidism . Eight patients sustained fractures ( six at the hip and two at other sites ) in the placebo group , and one hip fracture occurred among treated patients ( odds ratio 9.8 ; p=0.0028 ) . CONCLUSION By increasing serum 1 , 25-[OH]2D concentrations , treatment with 1α(OH)D3 can reduce the risk of hip and other non-vertebral fractures in osteoporotic elderly patients with Parkinson ’s disease by slowing the loss of bone mineral densities Objectives : To assess the effectiveness of a multivitamin ( MV ) tablet on nutritional status , quantitative heel ultrasound ( QUS ) , mobility , muscle strength and falls . The design comprised two groups matched on mobility levels , r and omized to receive a daily MV or placebo ( P ) tablet for 6 months . The setting was an Australian residential care facility . Subjects : A total of 92 aged care residents . Serum micronutrients , body weight , QUS , rate of falls , h and grip strength , and the timed up and go test were assessed at baseline and 6 months . Results : A total of 49 participants consumed a MV and 43 , a matched P for 6 months . There was a greater increase in the MV vs P group for serum 25(OH)D ( mean difference±st and ard error , 33.4±2.6 nmol l−1 ) , folate ( 13.4±2.8 nmol l−1 ) , and vitamin B12 ( 178.0±40.3 pmol l−1 ) ( all P<0.001 ) . Adequate 25(OH)D concentrations ( ⩾50 nmol l−1 ) were found among 77 % of participants in the MV group vs 10 % taking P ( P<0.001 ) . Adjusting for baseline levels , the increase in QUS was greater in the MV vs P group ( 3.0±2.0 dB MHz−1 vs −2.9±2.1 dB MHz−1 , respectively , P=0.041 ) . There was a trend towards a 63 % lower mean number of falls in the MV vs P group ( 0.3±0.1 falls vs 0.8±0.3 falls , P=0.078 ) . Conclusions : MV supplementation raised serum vitamin B12 and folate concentrations and increased serum 25(OH)D , which was accompanied by an apparent positive effect on bone density . We also found a trend towards a reduction in falls and this could contribute to a reduction in fractures The National Institutes of Health 's consensus conference ( 1 ) defined osteoporosis as a skeletal disorder characterized by compromised bone strength predisposing to an increased risk for fracture . Bone strength reflects the integration of two main features : bone density and bone quality .Bone quality refers to architecture , turnover , damage accumulation ( e.g. , microfractures ) , and mineralization . Although osteoporosis can affect any bone , the hip , spine , and wrist are most likely to be affected . Osteoporosis affects an estimated 44 million Americans or 55 % of people 50 years of age or older . Another 34 million Americans are estimated to have low bone mass , meaning that they are at an increased risk for osteoporosis . Osteoporosis can be diagnosed by the occurrence of fragility fracture . In patients without fragility fracture , osteoporosis is often diagnosed by low bone density . Dual x-ray absorptiometry ( DXA ) is the current gold st and ard test for diagnosing osteoporosis in people without an osteoporotic fracture . Dual x-ray absorptiometry results are scored as st and ard deviations ( SDs ) from a young healthy norm ( usually female ) and reported as T-scores . For example , a T-score of 2 indicates a bone mineral density that is 2 SDs below the comparative norm . The international reference st and ard for the description of osteoporosis in postmenopausal women and in men age 50 years or older is a femoral neck bone mineral density of 2.5 SD or more below the young female adult mean ( 2 ) . Low bone density , as measured by DXA , is an imperfect predictor of fracture risk , identifying fewer than half the people who go on to have an osteoporotic fracture . Screening guidelines for women are well established ( 3 ) , and the American College of Physicians ( ACP ) recently published guidelines on screening for men ( 4 ) . This guideline presents the available evidence on various pharmacologic treatments to prevent fractures in men and women with low bone density or osteoporosis . Medications used to treat osteoporosis may affect different parts of the skeletal system differently , and efficacy for vertebral fractures does not necessarily imply efficacy for nonvertebral fractures . The target audience for this guideline is all clinicians and the target patient population is all adult men and women with low bone density or osteoporosis . These recommendations are based on the systematic evidence review by MacLean and colleagues ( 5 ) and the Agency for Healthcare Research and Quality sponsored Southern California Evidence -Based Practice Center evidence report ( 6 ) . The drugs currently approved for prevention of osteoporosis include alendronate , ib and ronate , risedronate , zoledronic acid , estrogen , and raloxifene . The drugs currently approved for treatment of osteoporosis include alendronate , ib and ronate , risedronate , calcitonin , teriparatide , zoledronic acid ( in postmenopausal women ) , and raloxifene . Testosterone , pamidronate , and etidronate are not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Methods The literature search done by MacLean and colleagues for the systematic review ( 5 ) included studies from MEDLINE ( 1966 to December 2006 ) , the ACP Journal Club data base , the Cochrane Central Register of Controlled Trials ( no date limits ) , the Cochrane Data base of Systematic Review s ( no date limits ) , Web sites of the United Kingdom National Institute of Health and Clinical Excellence ( no date limits ) , and the United Kingdom Health Technology Assessment Program ( January 1998 to December 2006 ) . The review ers limited their search to English- language publications and human studies . They derived evidence for comparative benefits of various treatments exclusively from r and omized , controlled trials , whereas they included evidence from other types of studies for short- and long-term harms . Two physicians independently abstract ed data about study population s , interventions , follow-up , and outcome ascertainment by using a structured form . For each group within a r and omized trial , a statistician extracted the sample size and number of persons reporting fractures . Two review ers , under the supervision of the statistician , independently abstract ed information about adverse events . The statistician or the principal investigator resolved disagreements . This guideline is based on an evaluation of 76 r and omized , controlled trials , 4 of which were identified in the up date d search , and 24 meta-analyses that were included in the efficacy analyses . The analyses of adverse events included 491 articles , representing 417 r and omized trials , 25 other controlled clinical trials , 11 open-label trials , 31 large observational studies , and 9 case reports of osteonecrosis among bisphosphonate users . MacLean and colleagues ' background article ( 5 ) includes details about the methods used for the systematic evidence review . The ACP rates the evidence and recommendations by using the Grading of Recommendations , Assessment , Development , and Evaluation ( GRADE ) system with minor modifications ( Table 1 ) . In addition , the evidence review ers used predefined criteria to assess the quality of systematic review s and r and omized trials , based on internal and external validity assessment s detailed in the Quality of Reporting of Meta-Analyses ( QUOROM ) statement ( 7 ) . Table 1 . The American College of Physicians ' Guideline Grading System The objective of this guideline is to synthesize the evidence for the following questions : What are the comparative benefits in fracture reduction among and also within the following treatments for low bone density : bisphosphonates , specifically alendronate , risedronate , etidronate , ib and ronate , pamidronate , and zoledronic acid ; calcitonin ; estrogen for women ; teriparatide ; selective estrogen receptor modulators ( SERMs ) , specifically raloxifene and tamoxifen ; testosterone for men ; vitamins and minerals , specifically vitamin D and calcium ; and the combination of calcium plus vitamin D ? How does fracture reduction result ing from treatments vary among individuals with different risks for fracture as determined by bone mineral density ( borderline , low , or severe ) , previous fractures ( prevention vs. treatment ) , age , sex , glucocorticoid use , and other factors ( such as community-dwelling vs. institutionalized or vitamin Ddeficient vs. not ) ? What are the short- and long-term harms ( adverse effects ) of these therapies , and do these vary by specific sub population s ? Comparative Benefits of Drugs versus Placebo in Fracture Reduction Evidence from 24 meta-analyses ( 830 ) and 35 additional r and omized trials published after the meta-analyses ( 3165 ) described the effect of 9 of the 14 agents ( alendronate , etidronate , risedronate , calcitonin , estrogen , teriparatide , raloxifene , calcium , and vitamin D ) on fracture incidence . For 4 agents ( ib and ronate , pamidronate , zoledronic acid , and tamoxifen ) , the review ers found no meta-analyses and instead gathered the evidence from 14 r and omized trials ( 6679 ) . No studies were found that reported fracture rates for testosterone . Three r and omized trials ( 35 , 80 , 81 ) and 1 meta- analysis ( 82 ) evaluated the combination of calcium plus vitamin D on fractures . Bisphosphonates Good- quality evidence showed that alendronate , etidronate , ib and ronate , and risedronate prevent vertebral fractures . In addition , evidence from good- quality studies demonstrated that both alendronate and risedronate prevent nonvertebral and hip fractures . Two large r and omized trials showed that zoledronic acid prevents vertebral and nonvertebral fractures in high-risk population s and reduces the risk for hip fracture ( 67 , 74 ) . Ib and ronate has not been shown to reduce nonvertebral fractures ( 68 ) . Of the 6 fairly small trials that looked at vertebral fractures , 1 demonstrated a statistically significant reduction in fractures with pamidronate relative to placebo ( 0.14 [ 95 % CI , 0.03 to 0.72 ] ) ( 73 ) . However , after these data were pooled , the pooled risk estimate for fractures for pamidronate relative to placebo was not significant ( 0.52 [ CI , 0.21 to 1.24 ] ) ( 6 ) . Calcitonin Fair- quality evidence shows that calcitonin reduces vertebral fractures ( 83 , 84 ) . Good- quality evidence indicates that calcitonin does not reduce nonvertebral fractures ( 13 , 16 ) . Estrogen Good- quality evidence shows that estrogen reduces the incidence of vertebral ( 29 , 85 ) , nonvertebral ( 86 ) , and hip fractures ( 85 ) . Teriparatide Good- quality evidence shows that teriparatide prevents vertebral fractures . The evidence related to teriparatide preventing nonvertebral fractures is mixed ; 1 large r and omized trial showed a reduction in nonvertebral fractures ( 34 ) but 2 small trials did not ( 87 , 88 ) . SERMs Good- quality evidence shows that raloxifene prevents vertebral fractures , but that tamoxifen has no effect on vertebral fractures ( 8991 ) . In addition , both raloxifene and tamoxifen had no effect on hip fractures ( 91 ) . Tamoxifen is not approved by the U.S. Food and Drug Administration for the treatment or prevention of osteoporosis . Testosterone No studies reported fracture rates for testosterone . Calcium and Vitamin D In the studies evaluated by MacLean and colleagues ( 5 ) , the evidence for the effect of calcium alone on reduction of fractures is complex . Most studies of pharmacologic agents for osteoporosis include calcium and vitamin D as part of the treatment regimen . Evidence from 1 meta- analysis ( 27 ) and several r and omized trials ( 35 , 48 , 51 , 92 ) showed no significant difference between calcium and placebo in preventing vertebral , nonvertebral , and hip fractures in postmenopausal women . However , nonadherence to therapy may influence this result , and 1 trial with a prespecified analysis of adherent patients found a reduction in fracture risk ( 48 ) . A recent meta- analysis ( 82 ) concluded that the relative risk ( RR ) for fracture with calcium alone was 0.90 ( CI , 0.80 to 1.00 ) , but it did not include a modestly large trial with negative results ( 35 ) . MacLean and colleagues ( 5 ) BACKGROUND In recent prospect i ve studies , higher homocysteine concentrations were shown to be a risk factor for osteoporotic fractures in older persons . Supplements containing folate and vitamins B-12 and B-6 lower homocysteine concentrations . OBJECTIVE The objective of the study was to determine in healthy older persons whether lowering homocysteine with B vitamins affects plasma biomarkers of bone turnover . DESIGN Healthy older persons ( n = 276 ; aged > or=65 y ) were r and omly assigned to receive either a daily supplement containing folate ( 1 mg ) , vitamin B-12 ( 500 microg ) , and vitamin B-6 ( 10 mg ) or a placebo for 2 y. Of these participants , we selected 135 with baseline homocysteine concentrations > 15.0 micromol/L , and we measured serum bone-specific alkaline phosphatase , a marker of bone formation , and bone-derived collagen fragments , a marker of bone resorption , at baseline and 2 y later . RESULTS At 2 y , plasma homocysteine concentrations were 5.2 mumol/L ( 95 % CI : 3.9 , 6.6 micromol/L ; P < 0.001 ) lower in the vitamin than in the placebo group . No significant differences were found in either serum bone-specific alkaline phosphatase ( -0.3 microg/L ; 95 % CI : -2.8 , 2.1 microg/L ; P = 0.79 ) or bone-derived collagen fragments ( -0.0 microg/L ; 95 % CI : -0.1 , 0.1 microg/L ; P = 0.76 ) between the vitamin and placebo groups , respectively , with 2 y of supplementation . CONCLUSION Supplementation with folate and vitamins B-6 and B-12 lowered plasma homocysteine but had no beneficial effect on bone turnover at the end of 2 y , as assessed by biomarkers of bone formation and resorption BACKGROUND Elevated plasma homocysteine concentrations are a risk factor for osteoporotic fractures . Lowering homocysteine with combined vitamin B-12 and folic acid supplementation may reduce fracture risk . OBJECTIVE This study [ B-vitamins for the PRevention Of Osteoporotic Fractures ( B-PROOF ) ] aim ed to determine whether vitamin B-12 and folic acid supplementation reduces osteoporotic fracture incidence in hyperhomocysteinemic elderly individuals . DESIGN This was a double-blind , r and omized , placebo-controlled trial in 2919 participants aged ≥65 y with elevated homocysteine concentrations ( 12 - 50 μmol/L ) . Participants were assigned to receive daily 500 μg vitamin B-12 plus 400 μg folic acid or placebo supplementation for 2 y. Both intervention and placebo tablets also contained 600 IU vitamin D3 . The primary endpoint was time to first osteoporotic fracture . Exploratory prespecified subgroup analyses were performed in men and women and in individuals younger than and older than age 80 y. Data were analyzed according to intention-to-treat and per- protocol principles . RESULTS Osteoporotic fractures occurred in 61 persons ( 4.2 % ) in the intervention group and 75 persons ( 5.1 % ) in the placebo group . Osteoporotic fracture risk was not significantly different between groups in the intention-to-treat analyses ( HR : 0.84 ; 95 % CI : 0.58 , 1.21 ) or per- protocol analyses ( HR : 0.81 ; 95 % CI : 0.54 , 1.21 ) . For persons aged > 80 y , in per- protocol analyses , osteoporotic fracture risk was lower in the intervention group than in the placebo group ( HR : 0.27 ; 95 % CI : 0.10 , 0.74 ) . The total number of adverse events ( including mortality ) did not differ between groups . However , 63 and 42 participants in the intervention and placebo groups , respectively , reported incident cancer ( HR : 1.56 ; 95 % CI : 1.04 , 2.31 ) . CONCLUSIONS These data show that combined vitamin B-12 and folic acid supplementation had no effect on osteoporotic fracture incidence in this elderly population . Exploratory subgroup analyses suggest a beneficial effect on osteoporotic fracture prevention in compliant persons aged > 80 y. However , treatment was also associated with increased incidence of cancer , although the study was not design ed for assessing cancer outcomes . Therefore , vitamin B-12 plus folic acid supplementation can not be recommended at present for fracture prevention in elderly people . The B-PROOF study was registered with the Netherl and s Trial Register ( trialregister.nl ) as NTR1333 and at clinical trials.gov as NCT00696414 Incidence of a fracture , particularly in the hip joint , is high in elderly women with Parkinson 's disease ( PD ) , and this is due to the immobilization-induced bone resorption and vitamin D deficiency with reduced bone mineral density ( BMD ) . The objective of this study was to address the possibility that treatment with alendronate and vitamin D2 may reduce the incidence of hip fractures in elderly women with PD . PD patients were r and omly assigned to daily treatment with 5 mg alendronate ( n = 144 ) or a placebo combined with 1,000 IU of vitamin D2 ( n = 144 ) and followed for 2 years . Incidence of hip fractures in the two patient groups during the 2-year follow-up period was studied . At baseline , both groups of patients had low BMD with high levels of serum-ionized calcium and urinary deoxypyridinoline ( D-Pyr ) . Hip fractures occurred in 14 patients in the placebo group and 4 in the alendronate group . The relative risk for hip fractures in the alendronate group as compared with the placebo group was 0.29 ( 95 % CI , 0.10 - 0.85 ) . The number of hip fracture per 1,000 patient-years was 14 and 49 for the alendronate and placebo groups , respectively . In the alendronate group , serum calcium and urinary D-Pyr levels decreased significantly during the follow-up period , while the levels in the placebo group were increased . BMD increased by 3.1 % in the alendronate group and decreased by 2.8 % in the placebo group ( P < 0.01 ) . Treatment with alendronate and vitamin D2 increases BMD in elderly women with PD and leads to the prevention of hip fractures Background Incidence of a fracture , particularly in the hip joint , is high in Parkinson 's disease ( PD ) , owing to the immobilisation-induced bone resorption and vitamin D deficiency with reduced bone mineral density ( BMD ) . The authors previously demonstrated the lowered incidence of hip fractures in PD by daily administration of risedronate and vitamin D. Methods This r and omised , double-blind , placebo-controlled study was conducted to determine the efficacy of 17.5 mg once-weekly risedronate in the prevention of hip fracture in women with PD . Patients were r and omly assigned to 17.5 mg risedronate once a week ( n=136 ) or a placebo ( n=136 ) combined with daily 1000 IU of ergocalciferol . Incidence of hip fractures was compared between the two groups during the 2-year follow-up . Results Hip fractures occurred in 15 patients in the placebo group and 3 patients in the risedronate group . The RR for hip fractures in the risedronate group as compared with the placebo group was 0.20 ( 95 % CI 0.06 to 0.66 ) . In the risedronate group , serum calcium levels decreased during the follow-up , while the levels in the placebo group increased . BMD increased by 3.4 % in the risedronate group and decreased by 3.2 % in the placebo group ( p<0.01 ) . Conclusions Treatment with once-weekly risedronate and ergocalciferol prevents hip fractures in older women with PD BACKGROUND There is a high incidence of hip fractures in patients after hemiplegic stroke . Bone mineral density is decreased on the hemiplegic side in patients after stroke , correlating with the immobilization-induced bone resorption , the degree of paralysis , and hypovitaminosis D. The purpose of this study is to evaluate the effectiveness of risedronate sodium , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in men 65 years or older after stroke . METHODS We conducted an 18-month r and omized double-blind trial . Of 280 male patients 65 years or older who were poststroke , 140 received a daily dose of 2.5 mg risedronate sodium and the other 140 received placebo . Incidence of hip fractures in the 2 groups was compared . RESULTS Ten patients sustained hip fractures in the placebo group , and 2 hip fractures occurred in the risedronate group . The relative risk of a hip fracture was 0.19 ( 95 % confidence interval , 0.04 - 0.89 ) . The number of patients needing the treatment was 16 ( 95 % confidence interval , 9 - 32 ) . Bone mineral density increased by 2.5 % in the risedronate group and decreased by 3.5 % in the placebo group ( P<.001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 58.7 % in the risedronate group and by 37.2 % in the placebo group . CONCLUSION Treatment with risedronate increases bone mineral density and reduces hip fractures in elderly men who are poststroke March 2013 • Volume 116 • Number 3 Copyright © 2013 International Anesthesia Research Society . DOI : 10.1213/ANE.0b013e31827ab7d8 Between 1999 and 2001 , Kranke et al. 1–3 published 3 articles highlighting concerns with data from the numerous studies published by Dr. Yoshitaka Fujii on postoperative nausea and vomiting ( PONV ) management . Approximately 10 years later , Toho University Faculty of Medicine started to investigate the credibility of 9 publications by Dr. Fujii and announced in March 2012 that 8 of those studies lacked appropriate ethics committee approval . The Japanese Society of Anesthesiologists ( JSA ) subsequently set up a special investigation committee to assess the allegations of scientific fraud . The committee investigated 212 articles and concluded that 172 studies were fabricated and 3 were not . For 37 articles , the JSA stated that the evidence was inconclusive as to whether or not the studies were fabricated . Based on fabrication of at least 172 studies , this likely represents the largest fraud in the history of anesthesia literature . The purpose of this editorial is to provide an overview of the scope of Dr. Fujii ’s publications relating to PONV , and the extent to which our knowledge and management of PONV have been affected by removing these data from the literature . Of the 249 articles published by Fujii , 122 dealt with PONV . Of these , 110 articles were r and omized controlled trials ( RCTs ) , and the remaining 12 articles were review s. Of the 110 PONV RCTs , all but 1 were determined to be fabricated by the JSA investigation . The sole study not found to be fabricated was among those with no evidence to prove whether it was fabricated . There are several common themes in Dr. Fujii ’s publications . Many of his studies were repeated in different patient population s using the same drugs or combination of drugs , and reporting very similar results . Using a meta-analytic approach , Carlisle4 demonstrated that there was almost no heterogeneity among the majority of outcomes in the studies published by Fujii ( I2 = 0 ) . The I2 test assesses the degree of heterogeneity among included studies . It can be interpreted as the percentage of the total variability in a set of effect sizes due to true heterogeneity , that is , between- studies variability . When testing similar drugs in different patient population s , some degree of heterogeneity is expected . For instance , among RCTs comparing granisetron versus metoclopramide , the I2 was 0 % in Fujii ’s studies for all the end points tested ( nausea , vomiting , nausea or vomiting , and need for rescue antiemetics ) compared with I2 ranging from 5 % to 51 % for studies by all other authors .4 The main focus of Dr. Fujii ’s fabricated publications has been granisetron , which was allegedly investigated in 70 of his published RCTs . This included single-dose studies , dose-finding studies , and comparisons with other antiemetics mainly ramosetron , droperidol , and metoclopramide , as well as comparisons of the combination of granisetron with dexamethasone or droperidol versus single agents . In Dr. Fujii ’s articles , granisetron was reported to be more effective than all those other antiemetics with the exception of ramosetron , which was more effective than granisetron from 24 to 48 hours after surgery , but had similar effectiveness from 0 to 24 hours.5 In his dose-ranging studies , the minimum effective dose for PONV prophylaxis was 40 μg/ kg in adults6 and children7 when given IV , 2 mg in adults8 and 40 μg/kg in children9 when given orally , and 20 μg/kg for the treatment of PONV in adults.10 In 2001 , Kranke et al.3 performed a meta- analysis on granisetron for PONV prophylaxis and found that Fujii ’s results differed from those reported by other centers . Specifically , pooled results from Fujii ’s studies suggested that low-dose granisetron ( ≤20 μg/kg ) was ineffective for PONV prophylaxis and only high doses ( > 20 μg/kg ) were effective . This was in contrast to pooled results from other centers where there was no difference in effectiveness between low-dose and high-dose granisetron . Furthermore , pooled results from the Fujii studies suggested much higher effectiveness of high-dose granisetron compared with other centers . More recent studies by other investigators have confirmed that granisetron doses as low as 0.1 mg/kg are effective for PONV prophylaxis in adults.11 In his meta- analysis comparing the results of the studies by Fujii with other authors , Carlisle4 reported that granisetron was 1.3 to 1.5 times more effective in RCTs by Fujii than by other authors . Similar to other literature , Fujii From the Department of Anesthesiology , Duke University Medical Center , Durham , North Carolina BACKGROUND There is a high incidence of hip fractures in patients with Parkinson disease ( PD ) . Bone mineral density ( BMD ) is decreased in patients with PD , correlating with the immobilization-induced bone resorption and hypovitaminosis D with compensatory hyperparathyroidism . OBJECTIVE To evaluate the effectiveness of risedronate , an inhibitor of bone resorption , on osteoporosis and the risk of hip fractures in elderly men with PD . METHODS This was a 2-year , r and omized , double-blind , placebo-controlled trial . In a prospect i ve study of patients with PD , 121 patients received a daily dose of 2.5 mg risedronate and vitamin D2 1,000 IU for 2 years , and the remaining 121 received placebo and vitamin D2 1,000 IU . Incidence of hip fractures was compared between the two groups . RESULTS Nine patients sustained hip fractures in the placebo group , and three hip fractures occurred in the risedronate group . The relative risk of a hip fracture in the risedronate group vs the placebo group was 0.33 ( 95 % CI , 0.09 to 1.20 ) . BMD increased by 2.2 % in the risedronate group and decreased by 2.9 % in the placebo group ( p < 0.0001 ) . Urinary deoxypyridinoline , a bone resorption marker , decreased by 46.7 % in the risedronate group and by 33.0 % in the placebo group . CONCLUSION Treatment with risedronate and vitamin D2 increases bone mineral density in elderly men with Parkinson disease and reduces the risk of hip fractures Low vitamin K status is associated with low BMD and increased fracture risk . Additionally , a specific menaquinone , menatetrenone ( MK4 ) , may reduce fracture risk . However , whether vitamin K plays a role in the skeletal health of North American women remains unclear . Moreover , various K vitamers ( e.g. , phylloquinone and MK4 ) may have differing skeletal effects . The objective of this study was to evaluate the impact of phylloquinone or MK4 treatment on markers of skeletal turnover and BMD in nonosteoporotic , postmenopausal , North American women . In this double-blind , placebo-controlled study , 381 postmenopausal women received phylloquinone ( 1 mg daily ) , MK4 ( 45 mg daily ) , or placebo for 12 mo . All participants received daily calcium and vitamin D(3 ) supplementation . Serum bone-specific alkaline phosphatase ( BSALP ) and n-telopeptide of type 1 collagen ( NTX ) were measured at baseline and 1 , 3 , 6 , and 12 mo . Lumbar spine and proximal femur BMD and proximal femur geometry were measured by DXA at baseline and 6 and 12 mo . At baseline , the three treatment groups did not differ in demographics or study endpoints . Compliance with calcium , phylloquinone , and MK4 treatment was 93 % , 93 % , and 87 % , respectively . Phylloquinone and MK4 treatment reduced serum undercarboxylated osteocalcin but did not alter BSALP or NTX . No effect of phylloquinone or MK4 on lumbar spine or proximal femur BMD or proximal femur geometric parameters was observed . This study does not support a role for vitamin K supplementation in osteoporosis prevention among healthy , postmenopausal , North American women receiving calcium and vitamin D supplementation OBJECTIVES To assess the effect of between-meal weekly risedronate and daily calcium 630 mg and vitamin D 400 IU on bone turnover markers . DESIGN R and omized , double-blind , placebo-controlled trial . SETTING Skilled nursing home ( NH ) . PARTICIPANTS Sixty skilled-NH residents ( 46 men , 14 women ) , mean age+/-st and ard deviation of 76+/-6 , were r and omized to receive risedronate 30 mg ( n=31 ) or matching placebo ( n=29 ) once weekly for 12 weeks . All received 315 mg calcium with 200 IU vitamin D twice daily . MEASUREMENTS Bone-specific alkaline phosphatase ( BSAP ) , N-telopeptide of type 1 collagen ( NTx ) , 25-hydroxyvitamin D ( 25OHD ) , and parathyroid hormone were measured at baseline and 6 and 12 weeks . RESULTS Risedronate reduced BSAP significantly more than placebo ( P<.05 ) at 6 weeks but not at 12 weeks ; no treatment effect on serum NTx was observed . Defining hypovitaminosis D as a serum 25OHD concentration below 32 ng/mL , 50 of 53 ( 94 % ) study participants were low at baseline ( mean 25OHD 19 ng/mL ) . Vitamin D levels remained insufficient in 74 % of participants after 12 weeks . CONCLUSION In this NH population , weekly risedronate administered using a between-meal dosing schedule reduced serum BSAP at 6 weeks of treatment ; this effect was not observed at 12 weeks . The overall lack of change in bone turnover markers suggests that this risedronate dose and schedule would not be expected to increase bone density or reduce fracture risk in this population . Hypovitaminosis D was common and not reliably corrected by 400 IU of vitamin D daily . Despite an extremely high osteoporotic fracture risk in NH residents , additional study is required to determine under which conditions pharmacological treatment is efficacious in this population and define approaches that assure vitamin D repletion A r and omized , placebo-controlled trial was performed to determine the effect of a vitamin D analog ( 1-alpha-hydroxyvitamin D(2 ) [ 1-alpha D(2 ) ] ) on the bone mineral density ( BMD ) in patients with chronic spinal cord injury ( SCI ) . Forty subjects with chronic complete motor SCI were enrolled . The mean plus or minus st and ard deviation age and duration of injury were 42 plus or minus 12 yr and 11 plus or minus 10 yr , respectively . Either 4 micrograms 1-alpha D(2 ) ( n = 19 ) or placebo ( n = 21 ) was administered daily for 24 mo . Metabolic markers of bone resorption and formation were obtained . Regional lower-limb dual-energy x-ray absorptiometry was performed at baseline and at 6 , 12 , 18 , and 24 mo . Leg BMD and percent change from baseline significantly increased at 6 ( percent change only ) , 12 , 18 , and 24 mo in the treatment group , but not in the placebo group . Urinary N-telopeptide , a marker of bone resorption , was significantly reduced during treatment with 1-alpha D(2 ) , but markers of bone formation were not changed Background Homocysteine has been postulated as a novel , potentially reversible risk factor for osteoporosis and related fractures . We evaluated whether homocysteine-lowering therapy with B-vitamins in patients with symptomatic cerebrovascular disease reduced the incidence of osteoporotic fractures . Methods VITAmins To Prevent Stroke ( VITATOPS ) was a prospect i ve r and omised double-blind placebo-controlled trial in which 8,164 patients with recent ( within 7 months ) stroke or transient ischemic attack were r and omly allocated to double-blind treatment with one tablet daily of either placebo ( n = 4,075 ) or B-vitamins ( folic acid 2 mg , vitamin B6 25 mg , vitamin B12 500 μg ; n = 4,089 ) . Patients were review ed every six months . Any osteoporotic fracture and osteoporotic hip fractures were secondary outcome events , and were review ed by a masked adjudication committee . Analysis was by intention to treat . Logistic regression was used to identify independent predictors of fracture . Results Participants had a mean age of 62.6 years ( SD 12.5 years ) and 64 % were male , 42 % of Western European descent and 75 % were functionally independent ( Oxford H and icap Scale of two or less ) . After a median duration of 2.8 years therapy and 3.4 years follow-up , there was no significant difference in the incidence of any osteoporotic fracture between participants assigned B-vitamins ( 67 [ 1.64 % ] ) and placebo ( 78 [ 1.91 % ] ; risk ratio [ RR ] 0.86 , 95 % confidence interval [ CI ] 0.62 - 1.18 ) or the incidence of hip fractures ( 34 [ 0.83 % ] B-vitamins vs. 36 [ 0.88 % ] placebo ; RR 0.94 , 95 % CI 0.59 - 1.5 ) . There was no significant impact of B-vitamin therapy on time to first fracture . Baseline homocysteine levels did not predict any osteoporotic fracture ( p = 0.43 ) . Independent predictors of any osteoporotic fracture were female sex , age > 64 years , Western European ethnicity and use of anti-osteoporosis medication at r and omization ( all p < 0.01 ) . Conclusions Once daily treatment with B-vitamins had no effect on incidence of osteoporotic fractures during a median of 3.4 years follow-up in patients with cerebrovascular disease . A modest effect of B-vitamin therapy is not excluded due to the low numbers of fracture outcome events . Trial registration Clinical trials.gov number : NCT00097669 and is rct n.org number : IS RCT N74743444 OBJECTIVE To compare two micronutrient ( vitamins and minerals ) formulas ( Berocca ™ and CNE ™ ) and assess their impact on emotions and stress related to the 6.3 earthquake on February 22(nd ) 2011 in Christchurch , New Zeal and . METHODS 91 adults experiencing heightened anxiety or stress 2 - 3 months following the earthquake were r and omized to Berocca ™ , CNE ™ low dose ( CNE4 ) , or CNE ™ high dose ( CNE8 ) , for 28 days and monitored weekly via on-line question naires and followed 1 month post-trial . A nonr and omized control group ( n = 25 ) completed question naires at baseline and 4 weeks . RESULTS All treatment groups experienced significant declines in psychological symptoms ( p < .001 ) . CNE ™ groups experienced greater reduction in intrusive thoughts as compared with Berocca ™ ( p = .05 ) , with no group differences on other measures of psychological symptoms . However , CNE8 group reported greater improvement in mood , anxiety , and energy ( p < .05 ) with twice as many reporting being " much " to " very much " improved and five times more likely to continue taking CNE ™ post-trial than Berocca ™ group . Treated participants had better outcomes on most measures over 4 weeks as compared to controls . CONCLUSIONS This study supports micronutrients as an inexpensive and practical treatment for acute stress following a natural disaster with a slight advantage to higher doses ACTRN 12611000460909 BACKGROUND The proportion of European elderly is expected to increase to 30 % in 2060 . Combining dietary components may modulate many processes involved in ageing . So , it is likely that a healthful diet approach might have greater favourable impact on age-related decline than individual dietary components . This paper describes the design of a healthful diet intervention on inflammageing and its consequences in the elderly . METHODS The NU-AGE study is a parallel r and omized one-year trial in 1250 apparently healthy , independently living European participants aged 65 - 80 years . Participants are r and omised into either the diet group or control group . Participants in the diet group received dietary advice aim ed at meeting the nutritional requirements of the ageing population . Special attention was paid to nutrients that may be inadequate or limiting in diets of elderly , such as vitamin D , vitamin B12 , and calcium . C-reactive protein is measured as primary outcome . DISCUSSION The NU-AGE study is the first dietary intervention investigating the effect of a healthful diet providing targeted nutritional recommendations for optimal health and quality of life in apparently healthy European elderly . Results of this intervention will provide evidence on the effect of a healthful diet on the prevention of age related decline Significant reduction in bone mineral density ( BMD ) occurs in patients with Parkinson 's disease ( PD ) , correlating with immobilization and with vitamin D deficiency , and increasing the risk of hip fracture , especially in elderly women . As a biological indicator of compromised vitamin K status , an increased serum concentration of undercarboxylated osteocalcin ( Oc ) has been associated with reduced BMD in the hip and an increased risk of fracture in otherwise healthy elderly women . We evaluated treatment with vitamin K(2 ) ( menatetrenone ; MK-4 ) in maintaining BMD and reducing the incidence of nonvertebral fractures in elderly female patients with PD . In a r and om and prospect i ve study of PD patients , 60 received 45 mg of MK-4 daily for 12 months , and the remaining 60 ( untreated group ) did not . At baseline , patients of both groups showed vitamin D and K(1 ) deficiencies , high serum levels of ionized calcium , and glutaminic residue ( Glu ) Oc , and low levels of parathyroid hormone ( PTH ) and 1,25-dihydroxyvitamin D [ 1,25-(OH)(2)D ] , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1,25-(OH)(2)D and compensatory PTH secretion . BMD in the second metacarpals increased by 0.9 % in the treated group and decreased by 4.3 % in the untreated group ( p < 0.0001 ) . Vitamin K(2 ) level increased by 259.8 % in the treated group . Correspondingly , significant decreases in Glu Oc and calcium were observed in the treated group , in association with an increase in both PTH and 1,25-(OH)(2)D. Ten patients sustained fractures ( eight at the hip and two at other sites ) in the untreated group , and one hip fracture occurred among treated patients ( p = 0.0082 ; odds ratio = 11.5 ) . The treatment with MK-4 can increase the BMD of vitamin D- and K-deficient bone by increasing vitamin K concentration , and it can also decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1,25-(OH)(2)D concentration BACKGROUND A high incidence of fractures , particularly of the hip , represents an important problem in patients with Alzheimer disease ( AD ) , who are prone to falls and have osteoporosis . We previously found that deficiency of 25-hydroxyvitamin D and compensatory hyperparathyroidism cause reduced bone mineral density in female patients with AD . We address the possibility that treatment with risedronate sodium and ergocalciferol plus calcium supplementation may reduce the incidence of nonvertebral fractures in elderly women with AD . METHODS A total of 500 elderly women with AD were r and omly assigned to daily treatment with 2.5 mg of risedronate sodium or a placebo , combined with 1000 IU of ergocalciferol and 1200 mg of elementary calcium , and followed up for 18 months . RESULTS At baseline , patients of both groups showed 25-hydroxyvitamin D deficiency with compensatory hyperparathyroidism . During the study period , bone mineral density in the risedronate group increased by 4.1 % and decreased by 0.9 % in the control group . Vertebral fractures occurred in 29 patients ( 24 hip fractures ) in the control group and 8 patients ( 5 hip fractures ) in the risedronate group . The relative risk in the risedronate group compared with the control group was 0.28 ( 95 % confidence interval , 0.13 - 0.59 ) . CONCLUSIONS Elderly patients with AD hypovitaminosis D are at increased risk for hip fracture . Treatment with risedronate and ergocalciferol may be safe and effective in reducing the risk of a fracture in elderly patients with AD CONTEXT Stroke increases the risk of subsequent hip fracture by 2 to 4 times . Hyperhomocysteinemia is a risk factor for both ischemic stroke and osteoporotic fractures in elderly men and women . Treatment with folate and mecobalamin ( vitamin B12 ) may improve hyperhomocysteinemia . OBJECTIVE To investigate whether treatment with folate and vitamin B12 reduces the incidence of hip fractures in patients with hemiplegia following stroke . DESIGN , SETTING , AND PATIENTS A double-blind , r and omized controlled study of 628 consecutive patients aged 65 years or older with residual hemiplegia at least 1 year following first ischemic stroke , who were recruited from a single Japanese hospital from April 1 , 2000 , to May 31 , 2001 . Patients were assigned to daily oral treatment with 5 mg of folate and 1500 microg of mecobalamin , or double placebo ; 559 completed the 2-year follow-up . MAIN OUTCOME MEASURE Incidence of hip fractures in the 2 patient groups during the 2-year follow-up . RESULTS At baseline , patients in both groups had high levels of plasma homocysteine and low levels of serum cobalamin and serum folate . After 2 years , plasma homocysteine levels decreased by 38 % in the treatment group and increased by 31 % in the placebo group ( P<.001 ) . The number of hip fractures per 1000 patient-years was 10 and 43 for the treatment and placebo groups , respectively ( P<.001 ) . The adjusted relative risk , absolute risk reduction , and the number needed to treat for hip fractures in the treatment vs placebo groups were 0.20 ( 95 % confidence interval [ CI ] , 0.08 - 0.50 ) , 7.1 % ( 95 % CI , 3.6%-10.8 % ) , and 14 ( 95 % CI , 9 - 28 ) , respectively . No significant adverse effects were reported . CONCLUSION In this Japanese population with a high baseline fracture risk , combined treatment with folate and vitamin B12 is safe and effective in reducing the risk of a hip fracture in elderly patients following stroke The effect of vitamin K2 ( menatetrenone ) on bone turnover was investigated in postmenopausal patients with osteoporosis . A 6-month open-label , r and omized prospect i ve study was conducted in 109 patients . The control group ( n = 53 ) received calcium aspartate ( 133.8 mg of elemental calcium daily ) , while the menatetrenone group ( n = 56 ) received 45 mg of menatetrenone daily for 6 months . Serum and urinary levels of bone turnover markers were monitored . The serum level of undercarboxylated osteocalcin ( uc-OC ) was significantly lower ( P < 0.001 ) in the menatetrenone group than in the control group ( at 1 month ) , while there was a higher level of osteocalcin containing gamma-carboxylated glutamic acid ( Gla-OC ) in the menatetrenone group than the control group ( P = 0.018 ) . Significant differences of uc-OC and Gla-OC between the two groups were observed from 1 month onward . In addition , a higher level of intact osteocalcin was found in the menatetrenone group compared with the control group after 6 months ( P = 0.006 ) . Assessment of bone resorption markers showed that menatetrenone therapy was associated with significantly higher urinary N-telopeptide of type I collagen ( NTX ) excretion compared with the control group after 6 months , while there was no significant difference of urinary deoxypyridinoline excretion between the two groups . In conclusion , one month of menatetrenone therapy enhanced the secretion and gamma-carboxylation of osteocalcin , while urinary NTX excretion was increased after 6 months of treatment . Further investigations are required to determine whether the effects of menatetrenone on bone turnover are associated with fracture prevention Purpose Serum level of under-carboxylated osteocalcin ( ucOC ) is considered a sensitive measure of vitamin K status , and ucOC levels are associated with bone mineral density ( BMD ) and fracture risk in elderly persons . The aim of this study was to assess the relationship between ucOC and BMD in early menopausal women . Methods The data reported here come from the enrolment in a double-blinded placebo-controlled r and omized trial comprising 334 healthy Norwegian women between 50 and 60 years , 1–5 years after menopause , not using warfarin or medication known to affect bone metabolism . Total hip , femoral neck , lumbar spine , and total body BMD and serum level of ucOC and total osteocalcin were measured , and information of lifestyle was collected through question naires . The association between ucOC and BMD at all measurement sites was assessed by multiple regression analyses adjusting for possible confounding variables . Results The absolute serum level of ucOC was significantly and negatively associated with BMD at all measurements sites , both in univariate analyses ( p < 0.01 ) and in multivariate analyses adjusting for years since menopause , smoking status and weight ( p < 0.01 ) . However , serum ucOC , expressed as percentage of the total osteocalcin level , was not associated with BMD at any site . Conclusions Achievement of adequate vitamin K nutritional intake is important , but ucOC expressed as percentage of total osteocalcin levels as reflection of vitamin K status does not seem to play a central role in determining BMD levels in early menopausal women Abstract Background : Hyperhomocysteinemia is a new risk factor for osteoporosis . This study analyzed the effect of a homocysteine (HCY)-lowering treatment in osteoporotic individuals . Methods : Osteoporotic subjects ( n=47 , 55–82 years ) were treated with either a combination of 2.5 mg folate , 0.5 mg vitamin B12 and 25 mg vitamin B6 or placebo . Bone mineral density ( BMD ) at lumbar spine and hip was measured at baseline and after 1 year . Urinary desoxypyridinoline cross-links ( DPD ) and plasma levels of tartrate resistant acid phosphatase ( TRAP ) , C-terminal cross-links of collagen I ( CTx ) , pro-collagen type I N-terminal peptide ( PINP ) and osteocalcin ( OC ) were measured after 0 , 4 , 8 and 12 months . Results : B-vitamin supplementation significantly reduced HCY ( 0 vs. 12 months : 13.6±4.8 vs. 8.9±2.4 μmol/L ) . Placebo treatment had no effect on HCY ( 0 vs. 12 months : 12.0±3.4 vs. 12.7±3.9μmol/L ) . BMD , TRAP , CTx , OC and PINP did not change throughout the study in both groups . Vitamin treatment decreased urinary DPD by –13 % ( p<0.01 ) after 8 and 12 months . In a sub-group analysis of hyperhomocysteinemic subjects ( HCY>15 μmol/L , n=8 ) , B-vitamin treatment tended to increase BMD at the lumbar spine , with a t-score from –2.7 to –1.7 , and to decrease OC and PINP by approximately 50 % . Conclusions : B-vitamin supplementation had no consistent effects on bone turnover or BMD . However , the situation may be different in patients with hyperhomocysteinemia . Clin Chem Lab Med 2007;45:1785–92 BACKGROUND AND PURPOSE It has been demonstrated that bone mass was significantly reduced on the hemiplegic side of stroke patients , which might increase their risk of hip fracture . We evaluated the efficacy of 1 alpha-hydroxyvitamin D3 [ 1 alpha (OH)D3 ] and supplemental elemental calcium in maintaining bone mass and decreasing the incidence of hip fractures after hemiplegic stroke . METHODS In a r and omized study , 64 patients with hemiplegia after stroke with a mean duration of illness of 4.8 years received either 1 microgram 1 alpha (OH)D3 daily ( treatment group , n = 30 ) or an inactive placebo ( placebo group , n = 34 ) for 6 months and were observed for this duration . Both groups received 300 mg of elemental calcium daily . The bone mineral density ( BMD ) and metacarpal index ( MCI ) in the second metacarpals were determined by computed x-ray densitometry . The incidence of hip fractures in these patients was recorded . RESULTS BMD on the hemiplegic side decreased by 2.4 % in the treatment group and 8.9 % in the placebo group ( P = .0021 ) , while BMD on the intact side increased by 3.5 % and decreased by 6.3 % in the treated and placebo groups , respectively ( P = .0177 ) . In the treatment group , the difference in BMD between hemiplegic and nonhemiplegic sides decreased significantly compared with that before r and omization . This difference increased in the placebo group . We observed a similar improvement in MCI in the treatment group but not in the placebo group . Four patients in the placebo group suffered a hip fracture compared with none in the treatment group ( P = .0362 ) . CONCLUSIONS Treatment with 1 alpha (OH)D3 and supplemental elemental calcium can reduce the risk of hip fractures and can prevent further decreases in BMD and MCI on the hemiplegic side of patients with a long-st and ing stroke . Treatment also may improve these indices on the intact side Significant reduction in bone mineral density ( BMD ) occurs in stroke patients on the hemiplegic and contralateral sides , correlating with the degree of paralysis and vitamin D and K deficiency due to malnutrition , and increasing the risk of hip fracture . We evaluated the efficacy of vitamin K2 ( menatetrenone : menaquinone-4 ; MK-4 ) in maintaining BMD by comparing serum biochemical indices of bone metabolism between treated and untreated patients . In a r and om and prospect i ve study , of 108 hemiplegic patients following stroke , 54 received 45 mg menatetrenone daily ( MK-4 group , n = 54 ) for 12 months , and the remaining 54 ( untreatment group ) did not . Nine patients excluded from the study . The BMD in the second metacarpals and serum indices of bone metabolism were determined . BMD on the hemiplegic side increased by 4.3 % in the MK-4 group and decreased by 4.7 % in the untreated group ( p < 0.0001 ) , while BMD on the intact side decreased by 0.9 % in the MK-4 group and by 2.7 % in the untreated group ( p < 0.0001 ) . At baseline , patients of both groups showed vitamin D and K1 deficiencies , high serum levels of ionized calcium , pyridinoline cross-linked carboxyterminal telopeptide of type I collagen ( ICTP ) , and low levels of parathyroid hormones ( PTH ) and bone Gla proteins ( BGP ) , indicating that immobilization-induced hypercalcemia inhibits renal synthesis of 1 , 25-dihydroxyvitamin D ( 1 , 25-[OH]2D ) and compensatory PTH secretion . Both vitamins K1 and K2 increased by 97.6 % and 666.9 % , respectively , in the MK-4 group . Correspondingly , a significant increase in BGP and decreases in both ICTP and calcium were observed in the MK-4 group , in association with a simultaneous increase in both PTH and 1 , 25-[OH]2D . One patient in the untreated group suffered from a hip fracture , compared with none in the MK-4 group . The treatment with MK-4 can increase the BMD of disused and vitamin D- and K-deficient hemiplegic bone by increasing the vitamin K concentration , and it also can decrease calcium levels through inhibition of bone resorption , result ing in an increase in 1 , 25-[OH]2D concentration PURPOSE Calcium has been shown to have positive effects on bone mineral density in postmenopausal women . However , these effects are small , it is unknown whether they are sustained with long-term use , they have not been shown with intention-to-treat analyses , and the evidence for fracture prevention with calcium monotherapy is inconsistent . METHODS A r and omized controlled trial of calcium ( 1 g/day as the citrate ) in 1471 healthy postmenopausal women ( aged 74+/-4 years ) was performed to assess the effects on bone density and fracture incidence over 5 years . RESULTS Follow-up was complete in 90 % of subjects , and average medication compliance was 55 % to 58 % . Calcium had a significant beneficial effect on bone density ( intention-to-treat analysis ) , with between-groups differences at 5 years of 1.8 % ( spine ) , 1.6 % ( total hip ) , and 1.2 % ( total body ) . Effects were greater in a per- protocol analysis ( 5-year differences of 2.3 % , 2.8 % , and 1.8 % , respectively ) . A total of 425 fractures occurred in 281 women . Hazard ratios , based on time to first fracture , were 0.90 ( 95 % confidence interval [ CI ] , 0.71 - 1.16 ) for any symptomatic fracture , 0.72 ( 95 % CI , 0.44 - 1.18 ) for vertebral , 3.55 ( 95 % CI , 1.31 - 9.63 ) for hip , and 0.65 ( 95 % CI , 0.41 - 1.04 ) for forearm fracture . Per- protocol analysis found respective hazard ratios of 0.86 ( 95 % CI , 0.64 - 1.17 ) , 0.62 ( 95 % CI , 0.33 - 1.16 ) , 3.24 ( 95 % CI , 0.65 - 16.1 ) , and 0.45 ( 95 % CI , 0.24 - 0.87 ) . Height loss was reduced by calcium in the per- protocol population ( P=.03 ) . Serum alkaline phosphatase and procollagen type-I N-terminal propeptide were lower in the calcium group at 5 years , but constipation was more common . CONCLUSIONS Calcium results in a sustained reduction in bone loss and turnover , but its effect on fracture remains uncertain . Poor long-term compliance limits its effectiveness Objectives To assess the impact of retraction on the citation of r and omized controlled trials . Methods We used an interrupted time-series with matched controls . PubMed , CINHAL , Google and the Retraction Watch Data base were search ed . We identified retracted publications reporting the results of r and omized controlled trials involving human participants with two years of available data before and after retraction . We obtained monthly citation counts across all articles for the 24 months before and after retraction , from Web of Science . We used a Poisson segmented regression to detect changes in the level and trend of citation following retraction . We also undertook a matched control analysis of unretracted r and omized controlled trials and a sensitivity analysis to account for cases of large-scale , well-advertised fraud . Results We identified 387 retracted r and omized controlled trial reports , of which 218 ( 56.3 % ) were included in the interrupted time-series analysis . A reduction of 22.9 % ( 95 % CI 4.0 % to 38.2 % , p = 0.02 ) was observed in the number of citations in the month after retraction , and a further reduction of 1.9 % ( 95 % CI 0.4 % to 3.5 % , p = 0.02 ) per month in the following 24 months , relative to the expected trend . There was no evidence of a statistically significant reduction among the matched controls . Authors with a large number of retractions saw a 48.2 % reduction at the time of retraction ( 95 % CI 17.7 % to 67.3 % , p = 0.01 ) . Other cases had a more gradual reduction with no change at the time of retraction and a 1.8 % reduction per month in the following 24 months ( 95 % CI 0.2 % to 3.4 % , p = 0.03 ) . Conclusions Retractions of r and omized controlled trial reports can be effective in reducing citations . Other factors , such as the scale of the retractions and media attention , may play a role in the effectiveness of the reduction CONTEXT Vitamin K has been implicated in bone health , primarily in observational studies . However , little is known about the role of phylloquinone supplementation on prevention of bone loss in men and women . OBJECTIVE The objective of this study was to determine the effect of 3-yr phylloquinone supplementation on change in bone mineral density ( BMD ) of the femoral neck bone in older men and women who were calcium and vitamin D replete . DESIGN , PARTICIPANTS , AND INTERVENTION In this 3-yr , double-blind , controlled trial , 452 men and women ( 60 - 80 yr ) were r and omized equally to receive a multivitamin that contained either 500 mug/d or no phylloquinone plus a daily calcium ( 600 mg elemental calcium ) and vitamin D ( 400 IU ) supplement . MAIN OUTCOME MEASURES Measurements of the femoral neck , spine ( L2-L4 ) , and total-body BMD , bone turnover , and vitamins K and D status were measured every 6 - 12 months . Intent-to-treat analysis was used to compare change in measures in 401 participants who completed the trial . RESULTS There were no differences in changes in BMD measurements at any of the anatomical sites measured between the two groups . The group that received the phylloquinone supplement had significantly higher phylloquinone and significantly lower percent undercarboxylated osteocalcin concentrations compared with the group that did not receive phylloquinone . No other biochemical measures differed between the two groups . CONCLUSIONS Phylloquinone supplementation in a dose attainable in the diet does not confer any additional benefit for bone health at the spine or hip when taken with recommended amounts of calcium and vitamin Description This guideline up date s the 2008 American College of Physicians ( ACP ) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women . This guideline is endorsed by the American Academy of Family Physicians . Methods The ACP Clinical Guidelines Committee based these recommendations on a systematic review of r and omized controlled trials ; systematic review s ; large observational studies ( for adverse events ) ; and case reports ( for rare events ) that were published between 2 January 2005 and 3 June 2011 . The review was up date d to July 2016 by using a machine-learning method , and a limited up date to October 2016 was done . Clinical outcomes evaluated were fractures and adverse events . This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density , including pharmaceutical prescriptions , calcium , vitamin D , and estrogen . Evidence was grade d according to the GRADE ( Grading of Recommendations Assessment , Development and Evaluation ) system . Target Audience and Patient Population The target audience for this guideline includes all clinicians . The target patient population includes men and women with low bone density and osteoporosis . Recommendation 1 ACP recommends that clinicians offer pharmacologic treatment with alendronate , risedronate , zoledronic acid , or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis . ( Grade : strong recommendation ; high- quality evidence ) . Recommendation 2 ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 3 ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinical ly recognized osteoporosis . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 4 ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women . ( Grade : weak recommendation ; low- quality evidence ) . Recommendation 5 ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women . ( Grade : strong recommendation ; moderate- quality evidence ) . Recommendation 6 ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences , fracture risk profile , and benefits , harms , and costs of medications . ( Grade : weak recommendation ; low- quality evidence ) |
12,119 | 28,429,459 | In people with acute stroke , GTN reduces blood pressure , increases heart rate and headache , but does not alter clinical outcome ( all based on high- quality evidence ) | BACKGROUND Nitric oxide ( NO ) has multiple effects that may be beneficial in acute stroke , including lowering blood pressure , and promoting reperfusion and cytoprotection .
Some forms of nitric oxide synthase inhibition ( NOS-I ) may also be beneficial .
However , high concentrations of NO are likely to be toxic to brain tissue .
This is an up date of a Cochrane review first published in 1998 , and last up date d in 2002 .
OBJECTIVES To assess the safety and efficacy of NO donors , L-arginine , and NOS-I in people with acute stroke . | Background and Purpose — Among patients with acute stroke , high blood pressure is often associated with poor outcome , although the reason is unclear . We analyzed data from the International Stroke Trial ( IST ) to explore the relationship between systolic blood pressure ( SBP ) , subsequent clinical events over the next 2 weeks , and functional outcome at 6 months in patients with acute stroke . Methods — We included in the analysis 17 398 patients from IST with confirmed ischemic stroke . A single measurement of SBP was made immediately before r and omization . Clinical events within 14 days of r and omization were recorded : recurrent ischemic stroke , symptomatic intracranial hemorrhage , death result ing from presumed cerebral edema , fatal coronary heart disease , and death . Survival and dependency were assessed at 6 months . Outcomes were adjusted for age , sex , clinical stroke syndrome , time to r and omization , consciousness level , atrial fibrillation , and treatment allocation ( aspirin , unfractionated heparin , both , or neither ) . Results — A U-shaped relationship was found between baseline SBP and both early death and late death or dependency : early death increased by 17.9 % for every 10 mm Hg below 150 mm Hg ( P < 0.0001 ) and by 3.8 % for every 10 mm Hg above 150 mm Hg ( P = 0.016 ) . The rate of recurrent ischemic stroke within 14 days increased by 4.2 % for every 10–mm Hg increase in SBP ( P = 0.023 ) ; this association was present in both fatal and nonfatal recurrence . Death result ing from presumed cerebral edema was independently associated with high SBP ( P = 0.004 ) . No relationship between symptomatic intracranial hemorrhage and SBP was seen . Low SBP was associated with a severe clinical stroke ( total anterior circulation syndrome ) and an excess of deaths from coronary heart disease ( P = 0.002 ) . Conclusions — Both high blood pressure and low blood pressure were independent prognostic factors for poor outcome , relationships that appear to be mediated in part by increased rates of early recurrence and death result ing from presumed cerebral edema in patients with high blood pressure and increased coronary heart disease events in those with low blood pressure . The occurrence of symptomatic intracranial hemorrhage within 14 days was independent of SBP Background and Purpose — The practicalities of doing ambulance-based trials where paramedics perform all aspects of a clinical trial involving patients with ultra-acute stroke have not been assessed . Methods — We performed a r and omized controlled trial with screening , consent , r and omization , and treatment performed by paramedics prior to hospitalization . Patients with probable ultra-acute stroke ( < 4 hours ) and systolic blood pressure ( SBP ) > 140 mm Hg were r and omized to transdermal glyceryl trinitrate ( GTN ; 5 mg/24 hours ) or none ( blinding under gauze dressing ) for 7 days with the first dose given by paramedics . The primary outcome was SBP at 2 hours . Results — Of a planned 80 patients , 41 ( 25 GTN , 16 no GTN ) were enrolled > 22 months with median age [ interquartile range ] 79 [ 16 ] years ; men 22 ( 54 % ) ; SBP 168 [ 46 ] ; final diagnosis : stroke 33 ( 80 % ) and transient ischemic attack 3 ( 7 % ) . Time to r and omization was 55 [ 75 ] minutes . After treatment with GTN versus no GTN , SBP at 2 hours was 153 [ 31 ] versus 174 [ 27 ] mm Hg , respectively , with difference −18 [ 30 ] mm Hg ( P=0.030 ) . GTN improved functional outcome with a shift in the modified Rankin Scale by 1 [ 3 ] point ( P=0.040 ) . The rates of death , 4 ( 16 % ) versus 6 ( 38 % ; P=0.15 ) , and serious adverse events , 14 ( 56 % ) versus 10 ( 63 % ; P=0.75 ) , did not differ between GTN and no GTN . Conclusions — Paramedics can successfully enroll patients with ultra-acute stroke into an ambulance-based trial . GTN reduces SBP at 2 hours and seems to be safe in ultra-acute stroke . A larger trial is needed to assess whether GTN improves functional outcome . Clinical Trial Registration — URL : http://www.controlled-trials.com/IS RCT N66434824/66434824 . Unique identifier : 66434824 Summary Background High blood pressure is associated with poor outcome after stroke . Whether blood pressure should be lowered early after stroke , and whether to continue or temporarily withdraw existing antihypertensive drugs , is not known . We assessed outcomes after stroke in patients given drugs to lower their blood pressure . Methods In our multicentre , partial-factorial trial , we r and omly assigned patients admitted to hospital with an acute ischaemic or haemorrhagic stroke and raised systolic blood pressure ( systolic 140–220 mm Hg ) to 7 days of transdermal glyceryl trinitrate ( 5 mg per day ) , started within 48 h of stroke onset , or to no glyceryl trinitrate ( control group ) . A subset of patients who were taking antihypertensive drugs before their stroke were also r and omly assigned to continue or stop taking these drugs . The primary outcome was function , assessed with the modified Rankin Scale at 90 days by observers masked to treatment assignment . This study is registered , number IS RCT N99414122 . Findings Between July 20 , 2001 , and Oct 14 , 2013 , we enrolled 4011 patients . Mean blood pressure was 167 ( SD 19 ) mm Hg/90 ( 13 ) mm Hg at baseline ( median 26 h [ 16–37 ] after stroke onset ) , and was significantly reduced on day 1 in 2000 patients allocated to glyceryl trinitrate compared with 2011 controls ( difference −7·0 [ 95 % CI −8·5 to −5·6 ] mm Hg/–3·5 [ –4·4 to −2·6 ] mm Hg ; both p<0·0001 ) , and on day 7 in 1053 patients allocated to continue antihypertensive drugs compared with 1044 patients r and omised to stop them ( difference −9·5 [ 95 % CI −11·8 to −7·2 ] mm Hg/–5·0 [ –6·4 to −3·7 ] mm Hg ; both p<0·0001 ) . Functional outcome at day 90 did not differ in either treatment comparison — the adjusted common odds ratio ( OR ) for worse outcome with glyceryl trinitrate versus no glyceryl trinitrate was 1·01 ( 95 % CI 0·91–1·13 ; p=0·83 ) , and with continue versus stop antihypertensive drugs OR was 1·05 ( 0·90–1·22 ; p=0·55 ) . Interpretation In patients with acute stroke and high blood pressure , transdermal glyceryl trinitrate lowered blood pressure and had acceptable safety but did not improve functional outcome . We show no evidence to support continuing prestroke antihypertensive drugs in patients in the first few days after acute stroke . Funding UK Medical Research Council BACKGROUND Whether rapid lowering of elevated blood pressure would improve the outcome in patients with intracerebral hemorrhage is not known . METHODS We r and omly assigned 2839 patients who had had a spontaneous intracerebral hemorrhage within the previous 6 hours and who had elevated systolic blood pressure to receive intensive treatment to lower their blood pressure ( with a target systolic level of < 140 mm Hg within 1 hour ) or guideline -recommended treatment ( with a target systolic level of < 180 mm Hg ) with the use of agents of the physician 's choosing . The primary outcome was death or major disability , which was defined as a score of 3 to 6 on the modified Rankin scale ( in which a score of 0 indicates no symptoms , a score of 5 indicates severe disability , and a score of 6 indicates death ) at 90 days . A prespecified ordinal analysis of the modified Rankin score was also performed . The rate of serious adverse events was compared between the two groups . RESULTS Among the 2794 participants for whom the primary outcome could be determined , 719 of 1382 participants ( 52.0 % ) receiving intensive treatment , as compared with 785 of 1412 ( 55.6 % ) receiving guideline -recommended treatment , had a primary outcome event ( odds ratio with intensive treatment , 0.87 ; 95 % confidence interval [ CI ] , 0.75 to 1.01 ; P=0.06 ) . The ordinal analysis showed significantly lower modified Rankin scores with intensive treatment ( odds ratio for greater disability , 0.87 ; 95 % CI , 0.77 to 1.00 ; P=0.04 ) . Mortality was 11.9 % in the group receiving intensive treatment and 12.0 % in the group receiving guideline -recommended treatment . Nonfatal serious adverse events occurred in 23.3 % and 23.6 % of the patients in the two groups , respectively . CONCLUSIONS In patients with intracerebral hemorrhage , intensive lowering of blood pressure did not result in a significant reduction in the rate of the primary outcome of death or severe disability . An ordinal analysis of modified Rankin scores indicated improved functional outcomes with intensive lowering of blood pressure . ( Funded by the National Health and Medical Research Council of Australia ; INTERACT2 Clinical Trials.gov number , NCT00716079 . ) High blood pressure is common during the acute phase of stroke and is associated with a poor outcome . However , the management of high blood pressure remains unclear . The ‘ Efficacy of Nitric Oxide in Stroke ’ trial tested whether transdermal glyceryl trinitrate , a nitric oxide donor that lowers blood pressure , is safe and effective in improving outcome after acute stroke . Efficacy of Nitric Oxide in Stroke is an international multicenter , prospect i ve , r and omized , single-blind , blinded endpoint trial , with funding from the UK Medical Research Council . Patients with acute ischemic stroke or intracerebral hemorrhage and systolic blood pressure 140–220 mmHg were r and omized to glyceryl trinitrate or no glyceryl trinitrate and , where relevant , to continue or stop prestroke antihypertensive therapy . The primary outcome is shift in modified Rankin Scale at three-months . Patients or relatives gave written informed ( proxy ) consent , and all sites had research ethics approval . Analyses will be done by intention to treat . This paper and attachment describe the trial 's statistical analysis plan , developed prior to unblinding of date . The statistical analysis plan contains design and methods for analyses , and unpopulated tables and figures for the two primary publications and some secondary publications . The data base will be locked in late February 2014 in preparation for presentation of the results in May 2014 . The data from the trial will improve the precision of the estimates of the overall treatment effects ( efficacy and safety ) of results from completed trials of blood pressure management in acute stroke , and provide the first large-scale r and omized evidence on transdermal glyceryl trinitrate , and of continuing ( vs. stopping ) prestroke antihypertensive medications , in acute stroke RATIONALE The management of perioperative period for patients with spontaneous intracerebral hemorrhage affects the prognosis . Elevated blood pressure is common in the patients with spontaneous intracerebral hemorrhage and related to a poor outcome . However , study on antihypertensive treatment for surgical patients with spontaneous intracerebral hemorrhage is insufficient . AIMS To determine if the intensive antihypertensive treatment improves the prognosis compared with the conservative antihypertensive treatment followed guidelines in perioperative period for patients with spontaneous intracerebral hemorrhage . DESIGN PATICH is a prospect i ve , parallel , r and omized , assessor-blinded trial . Two hundred eligible patients will be assigned to the intensive group and conservative group r and omly . Patients allocated to the intensive group will receive an intensive antihypertensive treatment aim ing to achieve a target systolic blood pressure of between 120 mmHg and 140 mmHg while the patients in the conservative group will receive conservative antihypertensive treatment as recommended by guidelines for 7 days . Operation will be conducted by well-trained surgeons and the best medical treatment will be given in all patients . Patients will be followed up at 7 days , 30 days , and 90 days . STUDY OUTCOMES Primary outcome of this study is the rate of rehemorrhage in 7 days after surgery . Secondary outcomes include death and dependency at 90 days incidence of ischemic stroke , separate rate of death and dependency at 90 days , health related quality of life ( HRQoL ) at 90 days , incidence of other vascular events , and days of hospitalization . Dependency is defined by a score of 3 - 5 based on the modified Rankin Scale ( mRS ) High blood pressure in acute stroke is common and appears to be associated with a poor outcome . Lowering blood pressure might therefore improve outcome , provided that cerebral perfusion is not compromised . We assessed the effects of glyceryl trinitrate ( GTN ) on cerebral and systemic hemodynamic measures in acute stroke . Ninety patients with acute ischemic or hemorrhagic stroke were r and omized within 72 hours of ictus to transdermal GTN given daily for 10 days ( either 5 mg , 5 mg for 4 days then 10 mg , or 10 mg ) or control . Twenty-four hour blood pressure monitoring , middle cerebral artery blood velocity , cardiac output , augmentation index , and plasma nitric oxide levels were each measured at baseline and then on days 1 , 4 , 5 , and 10 . The primary outcome was blood pressure on day 1 . We found that GTN lowered mean peripheral arterial blood pressure on day 1 by 5.3 % to 6.7 % in a dose dependent manner as compared with control ( mean , SD ) : control , 108.8 ( 15.1 ) mmHg ; 5 mg , 102.5 ( 13.9 ) mmHg ; 5/10 mg , 103.4 ( 14.9 ) mmHg ; 10 mg , 101.5 ( 12.6 ) mmHg ; ( P = .005 ) . Increasing the dose from 5 to 10 mg on day 5 result ed in an overall reduction in blood pressure of 11.4 % as compared with leaving the dose at 5 mg ( P = .006 ) . GTN reduced peripheral pulse pressure , central aortic blood pressure , pulse pressure , and augmentation index on day 1 . Middle cerebral artery blood velocity and pulsatility index in the affected hemisphere , cardiac output , systemic peripheral resistance , and plasma nitric oxide levels were not altered by GTN . Treatment with GTN was associated with headache : control 0 ( 0 % ) , GTN 9 ( 15 % ) ( P = .027 ) ; no negative effect on end-of-treatment death or deterioration , or 3 month death or dependency was discernable . GTN reduced peripheral blood pressure in a dose-dependent fashion in patients with acute stroke at day 1 and also reduced central blood pressure and augmentation index . In contrast , GTN did not alter middle cerebral artery blood velocity or pulsatility index in the affected hemispheres , suggesting that cerebral blood flow did not change . A trial assessing the effect of lowering blood pressure with GTN on safety and functional outcome in patients with acute stroke is now warranted Background . Time from acute stroke to enrolment in clinical trials needs to be reduced to improve the chances of finding effective treatments . No completed r and omised controlled trials of ambulance-based treatment for acute stroke have been reported in the UK , and the practicalities of recruiting , consenting , and treating patients are unknown . Methods . RIGHT is an ambulance based , single-blind , r and omised controlled trial with blinded- outcome assessment . The trial will assess feasibility of using ambulance services to deliver ultra-acute stroke treatments ; a secondary aim is to assess the effect of glyceryl trinitrate ( GTN ) on haemodynamic variables and functional outcomes . Initial consent , r and omisation , and treatment are performed by paramedics prior to hospitalisation . Patients with ultra-acute stroke ( ≤4 hours of onset ) are r and omised to transdermal GTN ( 5 mg/24 hours ) or gauze dressing daily for 7 days . The primary outcome is systolic blood pressure at 2 hours . Secondary outcomes include feasibility , haemodynamics , dependency , and other functional outcomes . A nested qualitative study is included . Trial Status . The trial has all relevant ethics and regulatory approvals and recruitment started on February 15 , 2010 . The trial stopped recruitment in December 2011 after 41 patients were recruited . Trial Registration . The trial registration number is IS RCT N66434824 and EudraCT number is 2007 - 004766 - 40 High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Lowering BP might improve outcome if it did not adversely affect cerebral blood flow ( CBF ) or cerebral perfusion pressure . We investigated the effect of glyceryl trinitrate ( [ GTN ] an NO donor ) on quantitative CBF , BP , and cerebral perfusion pressure in patients with recent stroke . Eighteen patients with recent ( < 5 days ) ischemic ( n=16 ) or hemorrhagic ( n=2 ) stroke were r and omly assigned ( 2:1 ) to transdermal GTN ( 5 mg ) or control . CBF ( global , hemispheric , arterial territory , and lesion , using xenon computed tomography ) and BP ( peripheral and central ) were measured before and 1 hour after treatment with GTN . The effects of GTN on CBF and BP were adjusted for baseline measurements ( ANCOVA ) . GTN lowered peripheral systolic BP by ( mean ) 23 mm Hg ( 95 % CI , 2 to 45 ; P=0.03 ) and central systolic BP by 22 mm Hg ( 95 % CI , 0 to 44 ; P=0.048 ) . In contrast , GTN did not alter CBF ( mL/min per 100 g ) : global −1.2 ( 95 % CI , −6.5 to 4.2 ; P=0.66 ) and ipsilateral hemisphere −1.4 ( 95 % CI , −7.6 to 4.9 ; P=0.65 ) or area of stroke oligemia , penumbra , or core ( as defined by critical CBF limits ) . Contralateral CBF did not change : hemisphere 0 ( 95 % CI , −7 to 6 ; P=0.96 ) . GTN did not alter cerebral perfusion pressure or zero-filling pressure . Significant reductions in BP after transdermal GTN are not associated with changes in CBF or cerebral perfusion pressure or cerebral steal in patients with recent stroke . Trials need to assess the effect of lowering BP on functional outcome STUDY OBJECTIVE Optimal practice s for recruiting , consenting , and r and omizing patients , and delivering treatment in out-of-hospital ultra-acute stroke trials , remain unclear . We aim to identify key barriers and facilitators relevant to the design and conduct of ambulance-based stroke trials and to formulate preliminary recommendations for the design of future trials . METHODS Using semistructured interviews , we investigated the experiences and challenges faced by paramedics who took part in a r and omized controlled trial in suspected ultra-acute stroke , the Rapid Intervention With Glyceryl Trinitrate in Hypertensive Stroke Trial ( RIGHT ) , in which recruitment , consent , r and omization , assessment , and treatment were delivered by paramedics before hospitalization . RESULTS We purposively selected a diversity sample of 14 of the 78 paramedics who participated in RIGHT . We identified 13 themes ( 7 facilitators and 6 barriers to out-of-hospital stroke research ) . A simple stroke diagnostic tool , use of proxy consent on behalf of patients , and straightforward trial processes were identified as the main facilitators . Recruitment became easier with each new r and omization attempt . Key barriers reported were informed consent in the emergency setting , lack of institutional support for research , learning curve and rarity ( each paramedic treats only a few eligible patients ) , and difficulty in attending training sessions . Interviewed paramedics were motivated to participate in research . CONCLUSION Ultra-acute stroke research in the out-of-hospital environment is feasible , but important barriers need to be addressed . Proxy consent by paramedics addresses some of the difficulties with the consent process in the out-of-hospital setting INTRODUCTION The National Institutes of Health Stroke Scale ( NIHSS ) and Sc and inavian Stroke Scale ( SSS ) are both vali date d measures of neurologic impairment and have been used in many acute stroke trials . Methods for interconverting SSS and NIHSS are needed . METHODS Conversion equations were developed using linear regression ( both unadjusted , and adjusted for age and sex ) using a r and om 50 % of the data at both baseline and 90 days . The remaining 50 % of data were used to test the accuracy of the models produced . RESULTS Data from 5 acute stroke trials ( 2004 patients ) were included . Fitted models at baseline were NIHSS = 25.68 - 0.43 * SSS ( R(2 ) = 0.57 , prediction error [ PE ] -0.2 , P = .20 ) , and SSS = 50.37 - 1.63 * NIHSS ( R(2 ) = 0.59 , PE 0.2 , P = .35 ) . The 90-day models were NIHSS = 22.99 - 0.39 * SSS ( R(2 ) = 0.82 , PE -0.3 , P = .001 ) , and SSS = 56.68 - 2.20 * NIHSS ( R(2 ) = 0.80 , PE -0.4 , P = .08 ) . Adjustment did not material ly improve the R(2 ) values . CONCLUSION Total scores for NIHSS and SSS may be interconverted with good precision ; the mathematic conversion equations may prove useful in clinical practice and in comparison of data from observational studies and r and omized trials High blood pressure ( BP ) is common in acute stroke and is independently associated with a poor outcome . Many patients with acute stroke are taking antihypertensive medications . To test the safety and efficacy of 7 days of transdermal glyceryl trinitrate ( GTN , 5 mg/day ) vs. no GTN in patients with acute stroke ; patients taking antihypertensive therapy immediately before their stroke are also r and omised to continue vs. stop this temporarily . ENOS is a prospect i ve international multicentre single-blind r and omised-controlled trial in 5000 patients with acute ( < 48 h of onset ) ischaemic or haemorrhagic stroke . The primary outcome is combined death and dependency ( modified Rankin scale > 2 ) at 90 days measured by blinded central telephone follow-up . Secondary outcomes include : BP over the 7 days of treatment ; death , impairment ( Sc and inavian stroke scale ) , recurrence , and neuroimaging at 7 days ; discharge disposition , disability ( Barthel index ) , cognition ( mini-mental status examination ) and quality of life ( EuroQoL ) . The sample size will allow an absolute difference in death/dependency of 5 % to be detected with 90 % power at 5 % significance for GTN versus no GTN . R and omisation and data collection are performed over a secure Internet site with real-time data validation . Neuroimaging and serious adverse events are adjudicated blinded to treatment BACKGROUND Malignant infa rct ion of the middle cerebral artery ( MCA ) is associated with an 80 % mortality rate . Non-r and omised studies have suggested that decompressive surgery reduces this mortality without increasing the number of severely disabled survivors . To obtain sufficient data as soon as possible to reliably estimate the effects of decompressive surgery , results from three European r and omised controlled trials ( DECIMAL , DESTINY , HAMLET ) were pooled . The trials were ongoing when the pooled analysis was planned . METHODS Individual data for patients aged between 18 years and 60 years , with space-occupying MCA infa rct ion , included in one of the three trials , and treated within 48 h after stroke onset were pooled for analysis . The protocol was design ed prospect ively when the trials were still recruiting patients and outcomes were defined without knowledge of the results of the individual trials . The primary outcome measure was the score on the modified Rankin scale ( mRS ) at 1 year dichotomised between favourable ( 0 - 4 ) and unfavourable ( 5 and death ) outcome . Secondary outcome measures included case fatality rate at 1 year and a dichotomisation of the mRS between 0 - 3 and 4 to death . Data analysis was done by an independent data monitoring committee . FINDINGS 93 patients were included in the pooled analysis . More patients in the decompressive-surgery group than in the control group had an mRS < or=4 ( 75%vs 24 % ; pooled absolute risk reduction 51 % [ 95 % CI 34 - 69 ] ) , an mRS < or=3 ( 43%vs 21 % ; 23 % [ 5 - 41 ] ) , and survived ( 78%vs 29 % ; 50 % [ 33 - 67 ] ) , indicating numbers needed to treat of two for survival with mRS < or=4 , four for survival with mRS < or=3 , and two for survival irrespective of functional outcome . The effect of surgery was highly consistent across the three trials . INTERPRETATION In patients with malignant MCA infa rct ion , decompressive surgery undertaken within 48 h of stroke onset reduces mortality and increases the number of patients with a favourable functional outcome . The decision to perform decompressive surgery should , however , be made on an individual basis in every patient The ACCESS ( Acute C and esartan Cilexetil Therapy in Stroke Survivors ) study found that administration of c and esartan in the acute phase of stroke confers a long-term benefit in patients who have sustained acute ischemic stroke . This treatment did not significantly reduce blood pressure ( BP ) during the acute phase , however . We assessed the short-term safety of reducing BP with renin-angiotensin system blockade in hypertensive patients who sustained acute ischemic stroke . Our r and omized study compared the effects of 14 days of oral c and esartan ( 4 mg/day ) , perindopril ( 4 mg/day ) , or conventional therapy ( topical nitrate only when systolic BP ( SBP ) was ≥220 mm Hg or diastolic BP ( DBP ) was ≥120 mm Hg ) administered to hypertensive patients within 72 hours of the onset of minor ischemic stroke . We assessed neurologic symptoms using the National Institutes of Health Stroke Scale and the modified Rankin Scale within 72 hours of stroke onset before and after drug therapy . A total of 40 patients completed the protocol . Therapy with c and esartan and perindopril reduced SBP/DBP values by 23/11 mm Hg ( SBP , P<.01 ; DBP , P=.07 ) and 14/0 mm Hg ( SBP , P=.07 ) , respectively , compared with conventional treatment . Neurologic symptoms worsened in 2 patients who received perindopril , which has no statistical significance , despite the BP reduction in patients given c and esartan or perindopril . Our findings indicate that low doses of c and esartan or perindopril safely reduce SBP in hypertensive patients with acute ischemic stroke OBJECTIVE The calcium channel blocker nicardipine ( NC ) is effective for acute control of hypertension . However , efficacy and safety in neurosurgical patients have not been evaluated . We sought to compare NC with the most commonly used agent , sodium nitroprusside ( SNP ) , in patients with subarachnoid or intracerebral hemorrhage . METHODS We performed a prospect i ve r and omized comparison of the safety and efficacy of NC and SNP in patients with subarachnoid or intracerebral hemorrhage . We assessed the number of dose adjustments per patient day , proportion of time within set blood pressure parameters , use of additional medications for blood pressure control , clinical outcome , and drug-related complications . RESULTS Two hundred patients were screened and 163 patients were r and omized , including 89 in the SNP group and 74 in the NC group . In 107 patients , intravenous blood pressure control was started ; 60 of these patients received SNP and 47 received NC . When analyzed by intent to treat , patients r and omized to NC had fewer dose adjustments per day : 5.7 versus 8.8 in the nitroprusside group ( P = 0.0012 , Wilcoxon rank-sum test ) . There were fewer additional medications per day to maintain blood pressure control in the NC group : 1.4 versus 1.9 for SNP ( P = 0.043 , Wilcoxon rank-sum test ) . Blood pressure control was similar ( NC , 66 % of the time within parameters ; SNP , 69 % ) . " As-treated " analysis maintained the apparent advantage of NC . CONCLUSION When used for control of hypertension in patients with subarachnoid or intracerebral hemorrhage , NC and SNP were both safe and effective , but patients on an NC drip required fewer dose adjustments and fewer additional medications Background A poor outcome after stroke is associated independently with high blood pressure during the acute phase ; however , relationships with other haemodynamic measures [ heart rate ( HR ) , pulse pressure ( PP ) , rate – pressure product ( RPP ) ] remain less clear . Methods The Tinzaparin in Acute Ischaemic Stroke Trial is a r and omised , controlled trial assessing the safety and efficacy of tinzaparin versus aspirin in 1484 patients with acute ischaemic stroke . Systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and HR measurements taken immediately prior to r and omization were averaged , and the mid-blood pressure ( MBP ) , PP , mean arterial pressure ( MAP ) , pulse pressure index , and RPP were calculated . The relationship between these haemodynamic measures and functional outcome ( death or dependency , modified Rankin Scale > 2 ) and early recurrent stroke , were studied with adjustment for baseline prognostic factors and treatment group . Odds ratios ( OR ) and 95 % confidence intervals ( CI ) refer to a change in haemodynamic measure by 10 points . Results A poor functional outcome was associated with SBP ( adjusted OR ; 1.11 ; 95 % CI , 1.03–1.21 ) , HR ( adjusted OR ; 1.15 ; 95 % CI , 1.00–1.31 ) , MBP ( adjusted OR ; 1.15 , 95 % CI , 1.03–1.29 ) , PP ( adjusted OR ; 1.14 ; 95 % CI , 1.02–1.26 ) , MAP ( adjusted OR ; 1.15 ; 95 % CI , 1.02–1.31 ) and RPP ( adjusted OR ; 1.01 ; 95 % CI , 1.00–1.02 ) . Early recurrent stroke was associated with SBP , DBP , MBP and MAP . Conclusions A poor outcome is independently associated with elevations in blood pressure , HR and their derived haemodynamic variables , including PP and the RPP . Agents that modify these measures may improve functional outcome after stroke Background and Purpose : Hypertension is a common medical complication in acute stroke and is associated with a poor outcome . However , no large trials have assessed the effect of lowering blood pressure ( BP ) on outcome , and it remains unclear how BP should be managed in acute stroke . We assessed , in a double-blind r and omised controlled trial , whether the nitric oxide ( NO ) donor glyceryl trinitrate ( GTN , a known systemic and cerebral vasodilator ) , would lower BP and alter platelet function . Methods : Thirty-seven patients with recent ( < 5 days ) ischaemic or haemorrhagic stroke were r and omised by minimisation to 12 days of daily treatment with transdermal GTN or matching placebo patches . Twenty-four-hour ambulatory BP was measured before and during GTN treatment at days 0 , 1 and 8 . Platelet aggregation and expression of adhesion molecules were assessed at the same time points . Functional outcome ( Rankin scale ) and case fatality were assessed at 3 months . Analysis was by intention-to-treat . Results : GTN significantly lowered BP by 13.0/5.2 mm Hg at day 1 and 9.3/5.0 mm Hg at day 8 . The lesser reduction at day 8 than day 1 suggests that tolerance to GTN was developing . Non-significant falls of 0.9/0.6 and 3.8/0.0 mm Hg occurred at days 1 and 8 , respectively , in the placebo group . GTN had no effect on heart rate , or platelet aggregation or expression of platelet adhesion molecules , including glycoproteins Ia , Ib , IIIa and P-selectin . Additionally , GTN did not alter case fatality or dependency , although the study was not powered for these outcomes . Conclusions : Transdermal GTN , an NO donor , lowered BP by 5–8 % , a clinical ly significant and relevant , but not excessive , degree in patients with acute stroke . However , GTN had no effect on platelet aggregation or expression of adhesion molecules . Since NO donors increase cerebral blood flow in patients with acute ischaemic stroke , GTN may be an appropriate drug for testing the effect of lowering BP on functional outcome Acute ischaemic stroke is characterised by reductions in local cerebral blood flow ( CBF ) and activation of circulating platelets and leucocytes . Nitric oxide is a vasodilator and can inhibit these circulating cells . The aim of this study was to assess the effect of nitric oxide on platelet function and regional CBF in patients with acute ischaemic stroke . Sodium nitroprusside ( SNP ) , a spontaneous nitric oxide donor , was administered at a dose which caused a 10 mm Hg fall in mean arterial blood pressure ( MABP ) in a pathophysiological study to 22 patients with acute ischaemic stroke and 12 matched control subjects . Platelet function ( whole blood aggregation and flow cytometry ) was assessed before and during SNP administration . Changes in regional CBF were measured using single photon emission computerised tomography ( SPECT ) scanning . SNP significantly reduced platelet aggregation in both the patient and control subject groups . Equally , the expression of platelet adhesion molecules P-selectin ( CD62 ) and glycoprotein ( GP ) GP IIIa ( CD61 ) were significantly reduced in both groups . GP Ia ( CDw49b ) expression was significantly attenuated in the patient but not in the control group . Four patients underwent SPECT scanning and improvements in local CBF corresponding to the penumbral area of the clinical stroke site were seen in 3 of these patients . A total of 24 regions of asymmetrical perfusion were examined , pre-SNP ( median ( SQR ) ) , 0.68 ( 0.14 ) vs. peri-SNP 0.78 ( 0.17 ) , 2p = 0.065 . SNP , given at a dose which reduced MABP by 10 mm Hg , significantly inhibited platelet aggregation and adhesion molecule expression . Improved regional CBF was seen in some patients . SNP is a c and i date therapeutic agent for patients with acute ischaemic stroke and warrants further study |
12,120 | 25,211,400 | In addition , one study comparing sertraline with nortriptyline ( a tricyclic antidepressant ) found no difference in effectiveness ( 109 participants ) .Side effects were experienced by a substantial proportion of women , but there was no evidence of a meaningful difference in the number of adverse effects between treatment arms in any study .
Pooled estimates for response and remission found that SSRIs were significantly more effective than placebo for women with postnatal depression .
There is also inadequate evidence on whether the benefits of antidepressants persist beyond eight weeks or whether they have short- or long-term adverse effects on breastfeeding infants . | BACKGROUND Postnatal depression is a common disorder that can have adverse short- and long-term effects on maternal morbidity , the new infant and the family as a whole .
Treatment is often largely by social support and psychological interventions .
It is not known whether antidepressants are an effective and safe choice for treatment of this disorder .
This review was undertaken to evaluate the effectiveness of different antidepressants and to compare their effectiveness with other forms of treatment , placebo or treatment as usual .
It is an up date of a review first published in 2001 .
OBJECTIVES To assess the effectiveness of antidepressant drugs in comparison with any other treatment ( psychological , psychosocial or pharmacological ) , placebo or treatment as usual for postnatal depression . | BACKGROUND Women who have suffered from one episode of postpartum-onset major depression ( PPMD ) experience increased risk for recurrence in the year following another birth . METHODS Non-depressed women ( N=51 ) who had at least one past episode of PPMD were recruited during pregnancy . After birth , subjects were assessed prospect ively each week for 20 weeks with the Hamilton Rating Scale for Depression and Research Diagnostic Criteria for recurrence of major depression . Evaluations were carried out at 24 , 36 , and 52 weeks to assess for episodes beyond 20 weeks postpartum . RESULTS The data revealed a clustering of cases , with five of the 21 recurrences ( 24 % ) occurring in the first 2 weeks . Thirteen of the 21 recurrences ( 67 % ) and 19/21 recurrences ( 90 % ) occurred in the first 20 and 28 weeks following birth , respectively . LIMITATIONS Although it is unusual for studies of this type to be prospect i ve , the sample size is relatively small . CONCLUSIONS The 1-year recurrence rate was 21/51 or 41 % , with a clustering of cases near delivery . All recurrences except two occurred by 28 weeks postpartum 1 Abstract 1.1 Background Suicide is a leading cause of perinatal maternal deaths in industrialised countries but there has been little research to investigate prevalence or correlates of postpartum suicidality . The Edinburgh Postnatal Depression Scale is widely used in primary and maternity services to screen for perinatal depressive disorders , and includes a question on suicidal ideation ( question 10 ) . We aim ed to investigate the prevalence , persistence and correlates of suicidal thoughts in postpartum women in the context of a r and omised controlled trial of treatments for postnatal depression.1.2 Methods Women in primary care were sent postal question naires at 6 weeks postpartum to screen for postnatal depression before recruitment into an RCT . The Edinburgh Postnatal Depression Scale ( EPDS ) was used to screen for postnatal depression and in those with high levels of symptoms , a home visit with a st and ardised psychiatric interview was carried out using the Clinical Interview Schedule-Revised version ( CIS-R ) . Other socio-demographic and clinical variables were measured , including functioning ( SF12 ) and quality of the marital relationship ( GRIMS ) . Women who entered the trial were followed up for 18 weeks.1.3 Results 9 % of 4,150 women who completed the EPDS question relating to suicidal ideation reported some suicidal ideation ( including hardly ever ) ; 4 % reported that the thought of harming themselves had occurred to them sometimes or quite often . In women who entered the r and omised trial and completed the EPDS question relating to suicidal ideation ( n = 253 ) , suicidal ideation was associated with younger age , higher parity and higher levels of depressive symptoms in the multivariate analysis . Endorsement of ' yes , quite often ' to question 10 on the EPDS was associated with affirming at least two CIS-R items on suicidality . We found no association between suicidal ideation and SF-12 physical or mental health or the EPDS total score at 18 weeks.1.4 Conclusions Healthcare professionals using the EPDS should be aware of the significant suicidality that is likely to be present in women endorsing ' yes , quite often ' to question 10 of the EPDS . However , suicidal ideation does not appear to predict poor outcomes in women being treated for postnatal depression . Trial registration Current Controlled Trials IS RCT N16479417 BACKGROUND : Postnatal depression is a common disorder , which can have profound short and long term effects on maternal morbidity , the new infant and the family as a whole . Social factors appear to be particularly important in the aetiology and prognosis of postnatal depression and treatment is often largely social support and psychological interventions . It is not known whether antidepressants are an effective and safe choice for treatment of this disorder . OBJECTIVES : To evaluate the effectiveness of different antidepressant drugs and compare their effectiveness with other forms of treatment . To assess any adverse effects of antidepressants in the mother or the nursing baby . SEARCH STRATEGY : The registers of clinical trials maintained and up date d by the Cochrane Depression , Anxiety and Neurosis Group and the Cochrane Pregnancy and Childbirth Group were search ed . Other data bases ( outlined below ) were also search ed and contacts were made with pharmaceutical companies and experts in the field . SELECTION CRITERIA : All trials were considered in which women with depression in the first six months postpartum were r and omised to receive antidepressants alone or in combination with another treatment , or to receive any other treatment including placebo . DATA COLLECTION AND ANALYSIS : Data was extracted independently from the trial reports by the review ers . Missing information was requested from investigators wherever possible . Data was sought to allow an " intention to treat " analysis . MAIN RESULTS : Only one trial could be included in this review , leaving most of the objectives of the review unfulfilled . Appleby et al ( 1997 ) reported that Fluoxetine was significantly more effective than placebo and , after an initial session of counselling , as effective as a full course of cognitive-behavioural counselling in the treatment of postnatal depression . There was no interaction between medication and counselling . REVIEW ER 'S CONCLUSIONS : Women with postnatal depression can be effectively treated with fluoxetine , which is as effective as a course of cognitive-behavioural counselling in the short-term . However , more trials with a longer follow-up period are needed to compare different antidepressants in the treatment of postnatal depression , and to compare antidepressant treatment with psychosocial interventions . This is an area that has been neglected despite the large public health impact described above OBJECTIVE The efficacy of antidepressants in the treatment of mild-to-moderate postpartum depression and the possible advantage of the combination of an antidepressant and psychotherapy have not been adequately studied . We hypothesized that psychotherapy and concurrent antidepressant treatment would be more effective than psychotherapy alone in the treatment of postpartum depression . METHOD Women diagnosed with mild-to-moderate severity postpartum depression according to DSM-IV-TR criteria were enrolled in an 8-week , r and omized , double-blind , placebo-controlled study . Participants received 12 sessions of focused brief dynamic psychotherapy ( BDP ) concurrently with 8-week sertraline or placebo treatment , followed by a 4-week open phase . Primary outcomes were depression scores measured by the Montgomery-Asberg Depression Rating Scale ( MADRS ) and remission rates . The study was conducted in a referral center from May 2008 to September 2010 . RESULTS Forty of 42 women r and omized into the study entered the intent-to-treat analysis . A significant time effect for the MADRS was observed ( F4,35 = 21.3 , P < .0001 ) ; however , no time-by-group effect was found for any outcome measure . Response rates were 70 % and 55 % for the drug and placebo groups , respectively , and remission rates were 65 % and 50 % , respectively , with no significant difference between groups . CONCLUSION While both treatment groups improved significantly , the results of the present study did not demonstrate a significant benefit for sertraline over placebo as an add-on treatment to focused BDP in mild-to-moderate postpartum depression . Because of the study 's small sample , the results can not be viewed as definitive , and a much larger study is needed to confirm these results . Furthermore , the promising potential of focused BDP as an intervention in this population should be studied under controlled conditions . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01028482 Difficulties in mother – child interaction are commonly observed in the context of postnatal depression . These difficulties may result in part from the negative cognitive bias present in depression , which may in turn lead to biased negative perceptions of the infant : in particular , these biases encompass the negative appraisal of facial expressions . Given the important role of early mother – child interactions in child development it is vital to investigate potential interventions that might be beneficial in ameliorating the negative cognitive bias . This study aim ed to examine the effects of two different antidepressants ( reboxetine and citalopram ) on the appraisal of infant facial expressions of emotion using a faces rating task , and on attention to infant emotion using an attentional probe . Thirty-nine volunteers were r and omly assigned to a double-blind 7-day intervention with either placebo , citalopram or reboxetine . There were significant positive effects on the appraisal of facial expressions ; participants assigned to the placebo group rated positive faces less positively than those either in the citalopram or in the reboxetine groups . However , there was no evidence that these drugs had an effect on attentional vigilance . If antidepressants are able to help a mother to perceive her infant ’s facial expressions as more positive , this may lead to more positive interactions , thereby potentially mitigating the negative effects of depression on infant development . These findings should be treated with caution until replicated in larger and clinical sample Background In the UK , 8–15 % of women suffer from postnatal depression with long term consequences for maternal mood and child development . Current guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . Previous literature suggests that women are reluctant to disclose symptoms of postnatal depression . This study aim ed to explore general practitioners ' ( GPs ) , health visitors ' and women 's views on the disclosure of symptoms which may indicate postnatal depression in primary care . Methods In-depth interviews with GPs , health visitors and women who were participating in a r and omised controlled trial of anti-depressants versus health visitor delivered non-directive counselling for the treatment of postnatal depression . Interviews were audio-taped and fully transcribed . Thematic analysis with an iterative approach was used , allowing the views of practitioners and patients to be explored and then compared . Results Nineteen GPs , 14 health visitors and 28 women were interviewed . A number of common themes were identified across all three data sets : underst and ing and negotiating the diagnosis of postnatal depression , hindering and facilitating disclosure , and the system of care . Both women and health professionals described postnatal depression in psychosocial terms : an adjustment reaction to change in life circumstances and the reality of motherhood not meeting personal expectations . Women described making a conscious decision about whether or not to disclose their feelings to their GP or health visitor . Health professionals described strategies used to hinder disclosure and described a reluctance to make a diagnosis of postnatal depression , as they had few personal re sources to manage women with postnatal depression themselves , and no services to which to refer women for further treatment . Conclusion To improve disclosure of symptoms in primary care , there should be a move away from question ing why health professionals do not make the diagnosis of depression and in response suggesting that education and training will improve skills and thus improve detection of depression . Improving the detection and management of postnatal depression in primary care requires recognition of the context in which women consult , and system changes that ensure health professionals work in an environment that can facilitate disclosure and that the necessary re sources for management are available . Trail Registration IS RCT N BACKGROUND The optimum way to improve the recognition and treatment of postnatal depression in developing countries is uncertain . We compared the effectiveness of a multicomponent intervention with usual care to treat postnatal depression in low-income mothers in primary -care clinics in Santiago , Chile . METHODS 230 mothers with major depression attending postnatal clinics were r and omly allocated to either a multicomponent intervention ( n=114 ) or usual care ( n=116 ) . The multicomponent intervention involved a psychoeducational group , treatment adherence support , and pharmacotherapy if needed . Usual care included all services normally available in the clinics , including antidepressant drugs , brief psychotherapeutic interventions , medical consultations , or external referral for specialty treatment . The primary outcome measure was the Edinburgh postnatal depression scale ( EPDS ) score at 3 and 6 months after r and omisation . Analysis was by intention to treat . This study is registered with Clinical Trials.gov , number NCT00518830 . FINDINGS 208 ( 90 % ) of women r and omly assigned to treatment groups completed assessment s. The crude mean EPDS score was lower for the multicomponent intervention group than for the usual care group at 3 months ( 8.5 [ 95 % CI 7.2 - 9.7 ] vs 12.8 [ 11.3 - 14.1 ] ) . Although these differences between groups decreased by 6 months , EPDS score remained better in multicomponent intervention group than in usual care group ( 10.9 [ 9.6 - 12.2 ] vs 12.5 [ 11.1 - 13.8 ] ) . The adjusted difference in mean EPDS between the two groups at 3 months was -4.5 ( 95 % CI -6.3 to -2.7 ; p<0.0001 ) . The decrease in the number of women taking antidepressants after 3 months was greater in the intervention group than in the usual care group ( multicomponent intervention from 60/101 [ 59 % ; 95 % CI 49 - 69 % ] to 38/106 [ 36 % ; 27 - 46 % ] ; usual care from 18/108 [ 17 % ; 10 - 25 % ] to 11/102 [ 11 % ; 6 - 19 % ] ) . INTERPRETATION Our findings suggest that low-income mothers with depression and who have newly born children could be effectively helped , even in low-income setting s , through multicomponent interventions . Further refinements to this intervention are needed to ensure treatment compliance after the acute phase Rationale Postpartum depression ( PMD ) occurs in roughly 10 % of postpartum women and negatively impacts the mother and her offspring , but there are few placebo-controlled studies of antidepressant treatment in this population . Objective The objective was this study is to compare the selective serotonin reuptake inhibitor ( SSRI ) sertraline to placebo for treating PMD . Methods This was a single-center , 6-week , r and omized double-blind placebo-controlled trial of sertraline with a 1-week placebo lead-in . The participants ( n = 38 ) were women with depression onset within 3 months of delivery ; a subset ( n = 27 ) met strict DSM-IV criteria for PMD ( onset within 4 weeks of delivery ) . The participants were prescribed sertraline 50 mg or placebo daily to a maximum of 200 mg/day . Primary outcome variables were the Hamilton Depression Rating Scale ( HAM-D ) and Clinical Global Impressions ( CGI ) scores , which were used to determine the rates of response and remission . Results Sertraline produced a significantly greater response rate ( 59 % ) than placebo ( 26 % ) and a more than twofold increased remission rate ( 53 % vs. 21 % ) . Mixed models did not reveal significant group by time effects , although in the subset of women who met the DSM-IV criteria , there was a statistically significant group by time effect for the HAM-D , Hamilton Anxiety Rating Scale ( HAM-A ) , and CGI . Conclusions Women with PMD are more likely to have a remission of their depression with sertraline treatment , a finding that is more pronounced in women who have onset of depression within 4 weeks of childbirth . These data support the continued use of 4 weeks for the DSM-5 postpartum onset specifier for major depressive disorder OBJECTIVE The primary aim of this article is to describe sexual concerns in postpartum women with DSM-IV diagnoses of major depressive disorder ( MDD ) before and during treatment with antidepressants in an 8-week double-blind r and omized trial . METHOD Seventy women aged 19 - 42 years participated and were r and omly assigned to either the tricyclic antidepressant nortriptyline ( N = 38 ) or the serotonin selective reuptake inhibitor sertraline ( N = 32 ) . Women completed the Arizona Sexual Experience Scale to evaluate sexual concerns at enrollment and weekly during the trial . The outcome measure for depression , Hamilton Rating Scale for Depression , was completed in clinical interviews at the same time points . Comparisons of demographic and other characteristics of women were completed with t tests for continuous measures and with chi-squared or Fisher exact statistics for categorical measures . Mixed-effects regressions were used to test for significance of the main effects of depression symptom scores , drug assignment , weeks treated with medication , and the interactions of these variables . Data were collected from April 1997 to April 2002 . RESULTS At entry into the r and omized trial , 73 % ( N = 51 ) of the women reported problems in 3 or more areas of sexual concern compared to 37 % ( N = 26 ) at week 8 . There were no significant differences at study entry in women r and omly assigned to nortriptyline compared to those r and omly assigned to sertraline in summary scores of sexual function nor in specific sexual concerns at any time point . At week 8 , women whose MDD remitted were more likely to report fewer ( < 3 ) sexual concerns than women whose MDD did not remit ( 76 % vs. 24 % , p = .006 ) , independent of drug assignment . CONCLUSIONS In postpartum women , sexual concerns are primarily affected by remission of depression rather than side effects of either a tricyclic or serotonergic antidepressant OBJECTIVE Approximately 6 % to 8 % of postpartum women suffer from major depressive disorder ( MDD ) , but only a few controlled trials have investigated the efficacy of pharmacologic treatments . The current study determined the relative efficacy of paroxetine compared to placebo in the treatment of acute postpartum MDD . METHOD This was an 8-week , multicenter , parallel , placebo-controlled trial of paroxetine for treatment of postpartum depression . Subjects were eligible if they had an onset of DSM-IV MDD after , but within 3 months of , delivery and had a minimum score of 16 on the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) at intake . Seventy women were r and omly assigned to either immediate-release paroxetine or matching placebo , and 31 completed the trial . Subjects were reassessed with the HAM-D-17 , the Inventory of Depressive Symptomatology-Self-Report ( IDS-SR ) form and the Clinical Global Impressions ( CGI ) scales . The study was conducted between 1997 and 2004 . RESULTS Both groups improved over time and did not differ significantly on the HAM-D-17 or IDS-SR at follow-up . However , greater improvement in overall mean + /- SD clinical severity was found for the paroxetine ( Clinical Global Impressions-Severity of Illness [ CGI-S ] score = 1.8 + /- 1.4 ) compared with the control group ( CGI-S score = 3.1 + /- 1.4 ; p = .05 ) . The paroxetine group also had a significantly higher rate of remission , compared to the placebo group ( 37 % vs. 15 % , odds ratio = 3.5 , 95 % CI = 1.1 to 11.5 ) . The rate of adverse effects did not differ significantly between groups . CONCLUSION Study results were limited by lower than expected enrollment and higher than anticipated attrition . Nonetheless , paroxetine treatment was associated with a significantly higher rate of remission among women with postpartum onset of MDD The primary purpose of this pilot study was to compare improvement of symptoms and role functioning in women with postpartum depression after 8 weeks of treatment with antidepressants . The study was a secondary data analysis from the preliminary data of a double blind , r and omized clinical trial . The participants ( n=61 ) were primarily Caucasian and slightly over half were married , first time mothers , and middle- to upper-middle-class . At intake , most participants were moderately to severely ill . At week one and week eight of the study , measures of symptoms and functioning were only moderately correlated . After 8 weeks of antidepressant treatment , symptoms and most measures of functional status improved ; however , improvement in one dimension did not imply improvement in the other . Recommendations are given for clinical practice and further research in this area BACKGROUND In the UK , 8 - 15 % of women suffer from postnatal depression , with long-term consequences for maternal mood and child development . Previous literature suggests that health visitors struggle with their conflicting roles with respect to mother and infant . Current policy is redirecting the emphasis and organisation of health visitor work , but guidelines state that health visitors and GPs should continue to have a major role in the detection and management of postnatal depression . AIM To explore the views of GPs and health visitors on the diagnosis and management of postnatal depression . DESIGN OF STUDY A qualitative study nested within a multicentre r and omised controlled trial . SETTING Nine primary care trusts in Bristol , Manchester , and London . METHOD In-depth interviews with GPs and health visitors from primary care trusts participating in a r and omised controlled trial of antidepressants versus health visitor-delivered non-directive counselling . Interviews were audiotaped and fully transcribed . Thematic analysis with an iterative approach was used to develop conceptual categories from the transcripts . RESULTS Nineteen GPs and 14 health visitors were interviewed . GPs and health visitors described their work in making and negotiating the diagnosis of postnatal depression , the value of a long-term relationship with the woman , and how labelling affects management of women with postnatal depression . Responders described how they viewed others ' roles in the management of postnatal depression , and how national policy and local organisational changes had an impact on patient care , so that no one health professional was assuming overall responsibility for the care of women with postnatal depression . CONCLUSION Ongoing organisational changes within primary care , such as the implementation of corporate working by health visitors , affect care provided to women after birth , which in turn has an impact on the diagnosis and management of postnatal depression OBJECTIVES To evaluate clinical effectiveness at 4 weeks of antidepressant therapy for mothers with postnatal depression ( PND ) compared with general supportive care ; to compare outcome at 18 weeks of those r and omised to antidepressant therapy with those r and omised to listening visits as the first intervention ( both groups were to be allowed to receive the alternative intervention after 4 weeks if the woman or her doctor so decided ) ; and to assess acceptability of antidepressants and listening visits to users and health professionals . DESIGN A pragmatic two-arm individually r and omised controlled trial . SETTING Participants were recruited from 77 general practice s : 21 in Bristol , 21 in south London and 35 in Manchester . PARTICIPANTS A total of 254 women who fulfilled International Classification of Diseases version 10 criteria for major depression in the first 6 postnatal months were recruited and r and omised . INTERVENTIONS Women were r and omised to receive either an antidepressant , usually a selective serotonin reuptake inhibitor prescribed by their general practitioner ( GP ) , or non-directive counselling ( listening visits ) from a specially trained research health visitor ( HV ) . The trial was design ed to compare antidepressants with general supportive care for the first 4 weeks , after which women allocated to listening visits commenced their sessions . It allowed for women to receive the alternative intervention if they had not responded to their allocated intervention or wished to change to , or add in , the alternative intervention at any time after 4 weeks . MAIN OUTCOME MEASURES The duration of the trial was 18 weeks . Primary outcome , measured at 4 weeks and 18 weeks post r and omisation , was the proportion of women improved on the Edinburgh Postnatal Depression Scale ( EPDS ) , that is scoring < 13 . Secondary outcomes were the EPDS measured as a continuous variable at 4 and 18 weeks , and scores on various other question naires . RESULTS At 4 weeks , women were more than twice as likely to have improved if they had been r and omised to antidepressants compared with listening visits , which started after the 4-week follow-up , i.e. after 4 weeks of general supportive care [ primary intention-to-treat ( ITT ) , 45 % versus 20 % ; odds ratio ( OR ) 3.4 , 95 % confidence interval ( CI ) 1.8 to 6.5 , p < 0.001 ] . Explanatory analyses emphasised these findings . At 18 weeks , ITT analysis revealed that the proportion of women improving was 11 % greater in the antidepressant group , but logistic regression analysis showed no clear benefit for one group over the other [ 62 % versus 51 % , OR 1.5 ( 95 % CI 0.8 to 2.6 ) , p = 0.19 ] . Overall , there was a difference between the groups in favour of the antidepressant group of about 25 percentage points at 4 weeks , which reduced at 18 weeks . No statistical support existed for a benefit of antidepressants at 18 weeks , but 95 % CIs could not rule out a clinical ly important benefit . It was difficult for GPs not to prescribe antidepressants to women r and omised to listening visits after the initial 4 weeks , so many women received both interventions in both groups by 18 weeks and consequently power was reduced . Qualitative interviews with women revealed a preference for listening visits but an acceptance that antidepressants might be necessary . They wished to be reassured that their GP and HV were offering continuity of care focusing on their particular set of circumstances . Interviews with GPs and HVs revealed lack of collaboration in managing care for women with PND ; neither professional group was willing to assume responsibility . CONCLUSIONS At 4 weeks , antidepressants were significantly superior to general supportive care . Trial design meant that by 18 weeks many of the women initially r and omised to listening visits were also receiving antidepressants , and more vice versa . The lack of evidence for differences at 18 weeks is likely to reflect a combination of reduced power and the considerable degree of switching across the two interventions . Qualitative study revealed that women found both antidepressants and listening visits effective depending on their circumstances and preferences . The trial indicates that early treatment with antidepressants leads to clinical benefit for women with PND BACKGROUND AND OBJECTIVE Clinicians often find it difficult to differentiate between subobtimal adherence and nonresponse to medical treatment if a patient 's clinical condition does not improve . This study aim ed to evaluate an adherence self-report tool to assess adherence to blood pressure lowering medication . STUDY DESIGN AND SETTING Participants were 245 patients with uncontrolled hypertension from 21 general practice s taking part in a r and omized trial . Prior to r and omization , participants were asked to indicate which of six descriptions ( adherence levels ) would most closely describe their medication taking and were given electronic medication monitors for 30 days . We used multivariable regression analysis to compare the adherence self-report tool with electronic monitoring . RESULTS There was strong evidence that a drop in one adherence level from level 1 ( highest level ) to level 2 and from level 2 to level 3 - 6 ( six being the lowest ) combined was associated with a decrease in timing compliance of approximately 5 % ( test for trend : P = 0.0004 ) . CONCLUSION Adherence assessed by a brief self-report tool was associated with timing compliance obtained through electronic monitoring in patients taking blood pressure lowering medication . Further research is required to investigate the validity of this tool in patients with lower adherence levels and in a nontrial population The aim of this prospect i ve study was to examine the etiology of post-traumatic stress symptoms following childbirth within a transactional framework of stress . Participants were women ( N = 1,499 ) from the Akershus Birth Cohort . These women were followed from pregnancy to 8 weeks postpartum . We modeled predisposing factors ( e.g. , fear of childbirth ) and precipitating factors ( subjective and objective birth experiences ) as predictors of post-traumatic stress symptoms . Post-traumatic stress symptoms were measured by means of the Impact of Event Scale , objective birth experiences by means of birth journals , and subjective birth experiences by means of three questions . A structural equation model showed that subjective birth experiences had the highest association with post-traumatic stress symptoms . Moreover , they mediated the effect of predisposing factors and objective birth experiences . The results suggest that women ’s subjective birth experiences are the most important factor in the development of post-traumatic stress symptoms following childbirth BACKGROUND Antidepressants are frequently prescribed by GPs for postnatal depression ( PND ) . Patients , however , may be reluctant to take medication and have concerns that result in poor treatment adherence . Few studies have explored women 's views and experiences of antidepressants as a treatment for PND . GPs need to underst and women 's views and experiences if they are to address their concerns and improve treatment adherence . OBJECTIVE To explore women 's views and experiences of antidepressants as a treatment for PND . METHODS In-depth interviews with 27 women in three UK cities who had been diagnosed with PND and taken part in a r and omized controlled trial . During the trial , participants could receive antidepressants and /or non-directive counselling . Data were analysed thematically . RESULTS Most participants stated that they had held negative views towards antidepressants at the time of r and omization . Some participants reported that , over the course of their illness , through time and contact with others , including health professionals , their views towards antidepressants had changed and that they had gone on to take medication . Most interviewees who had taken antidepressants reported benefits , although some remained concerned about taking medication . CONCLUSION Women 's views of antidepressants can change in response to their treatment options and experiences , the views of friends and relatives and their contact with health professionals . GPs should assess women 's concerns about antidepressants prior to prescribing them for PND and should provide regular follow-up for women on medication . This should lead to greater treatment adherence and thus earlier resolution of symptoms AIMS The ability to mother her infant is reduced in a woman with postpartum depression ( PPD ) . Although antidepressant treatment effectively improves depressive symptoms , various domains of functioning , for example , work and relationships , do not universally improve with treatment . In this pilot study , we investigated whether maternal role functioning improved with antidepressant treatment in women with PPD . METHODS The pilot study was an exploratory analysis of a larger study . A subset of women ( n = 27 ) from a r and omized clinical trial ( double-blind , 8-week trial of nortriptyline compared with sertraline ) completed three outcome measures of maternal role functioning : gratification in the maternal role , the Infant Care Survey ( ICS ) , and videotapes of maternal-infant interaction . The tapes were analyzed using the Child and Caregiver Mutual Regulation Coding Scale and Noldus Behavioral Coding Software . RESULTS The two antidepressants were equally efficacious in decreasing depressive symptoms and improving overall functioning and gratification in the maternal role . Differences between times 1 and 2 in the mother-infant interactions were related to time ( increasing age of the infant ) and not assignment of antidepressant or remission of depression . CONCLUSIONS Effective treatment with two antidepressants improves gratification in the maternal role but not self-efficacy or maternal-infant interaction in women with PPD . Results of the study can help women and their healthcare providers to weigh the benefits of short-term antidepressant treatment in the postpartum period . Future studies should consider outcomes related to a longer duration of treatment BACKGROUND Approximately 10 % to 16 % of women experience a major depressive episode after childbirth . A significant proportion of these women also suffer from comorbid anxiety disorders . The purpose of this study was to evaluate whether the addition of cognitive-behavioral therapy ( CBT ) to st and ard antidepressant therapy offers additional benefits in the treatment of post-partum depression with comorbid anxiety disorders . METHOD Thirty-five women referred to a tertiary care hospital outpatient program with a DSM-IV diagnosis of postpartum depression with comorbid anxiety disorder were r and omly assigned to 1 of 2 treatment groups-paroxetine-only monotherapy group ( N = 16 ) or paroxetine plus 12 sessions of CBT combination therapy group ( N = 19)-for a 12-week trial . Progress was monitored by a psychiatrist blinded to treatment group , using the Hamilton Rating Scale for Depression , Hamilton Rating Scale for Anxiety , Yale-Brown Obsessive Compulsive Scale , Clinical Global Impressions scale , and Edinburgh Postnatal Depression Scale . Data were analyzed using 2-tailed statistical tests at an alpha level of.05 . The study was conducted from April 1 , 2002 , to June 30 , 2003 . RESULTS Both treatment groups showed a highly significant improvement ( p < .01 ) in mood and anxiety symptoms . Groups did not differ significantly in week of recovery , dose of paroxetine at remission , or measures of depression , anxiety , and obsessive-compulsive symptoms at outcome . CONCLUSION Antidepressant monotherapy and combination therapy with antidepressants and CBT were both efficacious in reducing depression and anxiety symptoms . However , in this sample of acutely depressed/anxious postpartum women , there were no additional benefits from combining the 2 treatment modalities . Further research into the efficacy of combination therapy in the treatment of moderate-to-severe depression with comorbid disorders in postpartum women is recommended BACKGROUND Few intervention studies of postnatal depression ( PND ) have evaluated accompanying changes in parenting , in spite of mounting evidence that exposure to chronic depression is detrimental to infant development . This study examined maternal attitudes and adjustment over the first postnatal year within a treatment trial . The aim was to examine whether maternal adjustment improved with earlier remission , and with combined medical and psychological treatment . METHODS As part of a multicentre pragmatic r and omised controlled trial of treatment for PND , mothers completed a measure of maternal adjustment and attitudes and the Edinburgh Postnatal Depression Scale at an initial home visit ( week 0 ) and three follow-ups ( weeks 4 , 18 and 44 ) . RESULTS Maternal attitudes and adjustment improved with PND remission ; earlier remission conferred no additional benefit by 44-week follow-up . In line with previous studies , no particular treatment modality ( antidepressant or health-visitor delivered non-directive counselling ) , or combination of treatments , was more effective for improving adjustment to parenthood . However , the earlier start of antidepressant treatment provided a short-term advantage for improving attitudes and reducing perceived stress . LIMITATIONS As a result of the study 's pragmatic trial design , there was high treatment non-compliance and no ' pure ' control group . More depressed mothers may have been less likely to complete the maternal adjustment and attitudes measure . CONCLUSIONS Effective treatment of PND is important not only for the mother 's wellbeing but also for healthy adjustment to parenthood . Provision of treatment choice and early antidepressant treatment are suggested for optimising maternal attitudes and adjustment OBJECTIVE To evaluate the efficacy of a controlled psycho-educational group ( PEG ) intervention for postnatal depression , compared with Routine Primary Care ( RPC ) . DESIGN AND METHOD The participants were 45 women scoring above 12 on the Edinburgh Postnatal Depression Scale who were allocated to the study conditions using block r and omization procedures . Short- and long-term changes in mood and psychosocial measures were assessed . RESULTS Compared with RPC , the PEG significantly reduced the level of depressive symptoms , but had no impact on psychosocial outcome . CONCLUSION A brief PEG is an effective form of treatment for women with low post-partum mood BACKGROUND Although maternal perinatal mental illnesses commonly present to and are primarily treated in general practice , few population -based estimates of this burden exist , and the most affected socioeconomic groups of pregnant women remain unclear . AIM To provide estimates of maternal depression , anxiety and serious mental illness ( SMI ) in UK general practice and quantify impacts of socioeconomic deprivation . DESIGN AND SETTING Cross-sectional analysis of prospect ively recorded general practice records from a UK-wide data base . METHOD A pregnancy ending in live birth was r and omly selected for every woman of childbearing age , 1994 - 2009 . Prevalence and diagnostic overlap of mental illnesses were calculated using a combination of medical diagnoses and psychotropic drug prescriptions . Socioeconomic deprivation was assessed using multivariate logistic regression , adjusting for calendar period and pregnancy history . RESULTS Among 116 457 women , 5.1 % presented with antenatal depression and 13.3 % with postnatal depression . Equivalent figures for anxiety were 2.6 % and 3.7 % and for SMI 1/1000 and 2/1000 women . Socioeconomic deprivation increased the risk of all mental illnesses , although this was more marked in older women . Those age 35 - 45 years in the most deprived group had 2.63 times the odds of antenatal depression ( 95 % confidence interval [ CI ] = 2.22 to 3.13 ) compared with the least deprived ; in women aged 15 - 25 years the increased odds associated with deprivation was more modest ( odds ratio = 1.35 , 95 % CI = 1.07 to 1.70 ) . Similar patterns were found for anxiety and SMI . CONCLUSION Strong socioeconomic inequalities in perinatal mental illness persist with increasing maternal age . Targeting detection and effective interventions to high-risk women may reduce inequity and avoid substantial psychiatric morbidity Abstract : Symptom reduction and improvement in functioning in women with postpartum major depression treated with a tricyclic antidepressant versus a serotonin reuptake inhibitor were compared . The design was a double-blind , 8-week comparative trial of nortriptyline ( NTP ) versus sertraline ( SERT ) with a 16-week continuation phase . Women aged 18 to 45 years with postpartum major depression and a 17-item Hamilton Rating Scale for Depression score of 18 or more were eligible . Subjects were r and omized to NTP or SERT and treated with a fixed-dosing strategy . Of 420 women interviewed , 109 eligible women received medication , and 95 provided follow-up data . The proportion of women who responded and remitted did not differ between drugs at 4 , 8 , or 24 weeks . Times to response and remission also did not differ . Psychosocial functioning improved similarly in both drug-treated groups of mothers . The total side effect burden of each drug was similar , although side effect profiles differed between agents . No clinical or demographic variables differentiated responders by drug . Women who were responders and remitters at week 8 could be identified earlier if they were treated with SERT than with NTP . Breast-fed infant serum levels were near or below the level of quantifiability for both agents |
12,121 | 25,524,944 | Low TS protein expression is a favorable predictive factor for better OS/PFS in NSCLC patients treated with TS-targeted drugs . | BACKGROUND It remains controversial whether thymidylate synthase ( TS ) protein expression is associated with survival for patients with non-small cell lung cancer ( NSCLC ) .
OBJECTIVE To evaluate prognostic and predictive significance of tumor TS protein level in NSCLC . | PURPOSE We assessed the prognostic importance of the level of thymidylate synthase ( TS ) expression in patients with primary rectal cancer and whether , for Dukes ' B and C cancer patients , the benefit of chemotherapy was associated with TS expression . PATIENTS AND METHODS The level of TS expression in the primary rectal cancers of 294 of 801 patients enrolled on protocol R-01 of the National Surgical Adjuvant Breast and Bowel Project ( NSABP ) was immunohistochemically assessed with the monoclonal antibody TS 106 . RESULTS Forty-nine percent of patients whose tumors had low TS levels ( n = 91 ) were disease free at 5 years compared with 27 % of patients with high levels of TS ( n = 203 ; P < .01 ) . Moreover , 60 % of patients with low TS levels were alive after 5 years compared with 40 % of patients with high TS levels ( P < .01 ) . The level of TS protein was significantly associated with Dukes ' stage ( P < .01 ) ; patients with a more advanced Dukes ' stage had a significantly higher level of TS . The level of TS expression remained prognostic for both disease-free survival ( P < .01 ) and survival ( P < .05 ) independent of Dukes ' stage and other pathologic characteristics evaluated . Thirty-eight percent and 54 % of patients with high TS levels ( n = 71 ) were disease free and alive , respectively , after 5 years when treated with chemotherapy , compared with 17 % and 31 % , respectively , of similar patients when treated with surgery alone ( n = 64 ) ( P < .01 ) . No difference was noted in disease-free survival ( P = .46 ) or survival ( P = .43 ) in patients with low TS levels . CONCLUSION The expression of TS is an important independent prognosticator of disease-free survival and survival in patients with rectal cancer . Adjuvant fluorouracil (5-FU)-based chemotherapy demonstrated significant improvement in disease-free and overall survival for patients with high TS levels . Prospect i ve studies measuring TS levels will be needed to underst and further the role of TS as a prognosticator of survival and chemotherapeutic benefit We performed a clinical study to identify biological markers useful for the treatment of resectable non-small-cell lung cancers ( NSCLCs ) . In all , 173 patients were studied . By immunohistochemistry , we evaluated the Ki-67 proliferation index , tumour vascularity , thymidylate synthase ( TS ) , vascular endothelial growth factor (VEGF)-A , VEGF-C , and E (epithelial)-cadherin . Concerning the survival of NSCLC patients , tumour vascularity ( P<0.01 ) , VEGF-A status ( P=0.03 ) , VEGF-C status ( P=0.03 ) , and E-cadherin status ( P=0.03 ) were significant prognostic factors in patients with stage I NSCLCs . The Ki-67 proliferation index ( P=0.02 ) and TS status ( P<0.01 ) were significant prognostic factors in patients with stage II – III NSCLCs . In patients with stage II – III NSCLCs , furthermore , the survival of UFT ( a combination of tegafur and uracil)-treated patients with TS-negative tumours was significantly better than those of any other patients . Biological markers associated with tumour angiogenesis or metastasis are useful for the detection of aggressive tumours among early-stage NSCLCs . Postoperative chemotherapy might be necessary in such tumours even in stage I. In contrast , tumour proliferation rate and TS status are useful markers for identifying less aggressive tumours in locally advanced NSCLCs . Thymidylate synthase expression is also a useful marker to evaluate responsiveness of UFT-based chemotherapy for these tumours Purpose : This phase II trial of pemetrexed explored potential correlations between treatment outcome ( antitumor activity ) and molecular target expression . Experimental Design : Chemonaïve patients with advanced breast cancer received up to three cycles of pemetrexed 500 mg/m2 ( 10-minute i.v . infusion ) on day 1 of a 21-day cycle , with folic acid and vitamin B12 supplementation . Tumors were surgically removed after the last cycle of pemetrexed as clinical ly indicated . Biopsies were taken at baseline , 24 hours after infusion in cycle 1 , and after cycle 3 . Results : Sixty-one women ( median age , 46 years ; range , 32 - 72 years ) were treated and were evaluable for response . Objective response rate was 31 % . Simple logistic regression suggested a potential relationship between mRNA expression of thymidylate synthase ( TS ) and pemetrexed response ( P = 0.103 ) . Based on threshold analysis , patients with “ low ” baseline TS ( ≤71 ) were more likely to respond to pemetrexed than patients with “ high ” baseline TS ( > 71 ) . Expression of baseline dihydrofolate reductase and glycinamide ribonucleotide formyl transferase tended to be higher in responders but this association was not significant ( P > 0.311 ) . TS expression increased significantly between baseline and biopsy 2 ( P = 0.004 ) and dropped to near baseline levels at biopsy 3 . Conversely , dihydrofolate reductase and glycinamide ribonucleotide formyl transferase decreased after pemetrexed chemotherapy . Conclusions : Our results suggest a potential association between “ low ” pretreatment TS expression levels and response to pemetrexed chemotherapy . Future trials examining expression levels of other genes important to the folate pathway and /or breast cancer may identify a more robust multigene profile that can better predict response to this novel antifolate The purpose of this study was to define the prognostic value of a group of molecular tumor markers in a well-staged population of patients treated with trimodality therapy for esophageal cancer . The original pretreatment paraffin-embedded endoscopic esophageal tumor biopsy material was obtained from 118 patients treated with concurrent cisplatin + 5-fluorouracil ( 5-FU ) + 45 Gy radiation followed by resection from 1986 until 1997 at the Duke University Comprehensive Cancer Center . Three markers of possible platinum chemotherapy association [ metallothionein ( MT ) , glutathione S-transferase-pi ( GST-pi ) , P-glycoprotein ( P-gp or multidrug resistance ) ] and one marker of possible 5-FU association [ thymidylate synthase ( TS ) ] were measured using immunohistochemistry . The median cancer-free survival was 25.0 months , with a significantly improved survival for the 38 patients who had a complete response ( P < 0.001 ) . High-level expression of GST-pi , P-gp , and TS were associated with a decreased survival . MT was not significant in this population . Multivariate analysis identified high-level expression in two of the platinum markers ( GST-pi and P-gp ) and the 5-FU marker TS as independent predictors of early recurrence and death . In conclusion , this investigation measured three possible markers associated with platinum and one possible marker associated with 5-FU in a cohort of esophageal cancer patients . Independent prognostic significance was observed , which suggests that it may be possible to predict which patients may benefit most from trimodality therapy . These data need to be reproduced in a prospect i ve investigation Introduction : In retrospective analyses of patients with nonsquamous non – small-cell lung cancer treated with pemetrexed , low thymidylate synthase ( TS ) expression is associated with better clinical outcomes . This phase II study explored this association prospect ively at the protein and mRNA-expression level . Methods : Treatment-naive patients with nonsquamous non – small-cell lung cancer ( stage IIIB/IV ) had four cycles of first-line chemotherapy with pemetrexed/cisplatin . Nonprogressing patients continued on pemetrexed maintenance until progression or maximum tolerability . TS expression ( nucleus/cytoplasm/total ) was assessed in diagnostic tissue sample s by immunohistochemistry ( IHC ; H-scores ) , and quantitative reverse-transcriptase polymerase chain reaction . Cox regression was used to assess the association between H-scores and progression-free/overall survival ( PFS/OS ) distribution estimated by the Kaplan – Meier method . Maximal & khgr;2 analysis identified optimal cutpoints between low TS- and high TS-expression groups , yielding maximal associations with PFS/OS . Results : The study enrolled 70 patients ; of these 43 ( 61.4 % ) started maintenance treatment . In 60 patients with valid H-scores , median ( m ) PFS was 5.5 ( 95 % confidence interval [ CI ] , 3.9–6.9 ) months , mOS was 9.6 ( 95 % CI , 7.3–15.7 ) months . Higher nuclear TS expression was significantly associated with shorter PFS and OS ( primary analysis IHC , PFS : p < 0.0001 ; hazard ratio per 1-unit increase : 1.015 ; 95%CI , 1.008–1.021 ) . At the optimal cutpoint of nuclear H-score ( 70 ) , mPFS in the low TS- versus high TS-expression groups was 7.1 ( 5.7–8.3 ) versus 2.6 ( 1.3–4.1 ) months ( p = 0.0015 ; hazard ratio = 0.28 ; 95%CI , 0.16–0.52 ; n = 40/20 ) . Trends were similar for cytoplasm H-scores , quantitative reverse-transcriptase polymerase chain reaction and other clinical endpoints ( OS , response , and disease control ) . Conclusions : The primary endpoint was met ; low TS expression was associated with longer PFS . Further r and omized studies are needed to explore nuclear TS IHC expression as a potential biomarker of clinical outcomes for pemetrexed treatment in larger patient cohorts Introduction : This study is to evaluate whether thymidylate synthase ( TS ) or thyroid transcription factor 1 ( TTF1 ) protein expression can predict clinical outcomes for pemetrexed-based chemotherapy in patients with nonsquamous non-small cell lung cancer ( NSCLC ) . Methods : Two hundred eighty-five consecutive patients with nonsquamous NSCLC treated with pemetrexed-based chemotherapy were immunohistochemically analyzed for the expressions of TS and TTF1 . Results : TS and TTF1 expression were successfully analyzed in 193 and 284 cases , respectively . Tumors with TS-negativity or TTF1-positivity were more frequent in patients who were female , younger , had adenocarcinoma , or had never smoked . Higher response rates for pemetrexed-based chemotherapy were associated with TS-negativity ( 33.7 % versus 14.1 % , p = 0.002 ) and TTF1-positivity ( 28.1 % versus 9.8 % , p < 0.001 ) . In univariate analysis , progression-free survival for pemetrexed-based chemotherapy was significantly longer in groups with adenocarcinoma ( 2.9 versus 1.4 months , p = 0.001 ) , TS-negativity ( 4.1 versus 2.0 months , p = 0.001 ) , and TTF1-positivity ( 3.8 versus 1.3 months , p < 0.001 ) . In multivariate analysis , TS-negativity ( hazard ratio [ HR ] = 0.70 ; 95 % confidence interval [ CI ] , 0.51–0.97 ) and TTF1-positivity ( HR = 0.51 ; 95 % CI , 0.35–0.73 ) were associated with longer progression-free survival . Patients with TTF1-positive tumors also had significantly longer overall survival times than patients with TTF1-negative tumors ( 25.4 versus 14.2 months , HR = 0.55 ; 95 % CI , 0.39–0.77 ) . Conclusions : Low TS or high TTF1 protein expression was significantly associated with better clinical outcomes in nonsquamous NSCLC patients who were treated with pemetrexed-based chemotherapy . The predictive role of TS or TTF1 expression should be further vali date d in a prospect i ve r and omized study BACKGROUND UFT ( tegafur + uracil ) has been reported to be effective as an adjuvant in postoperative chemotherapy for non-small cell lung cancer ( NSCLC ) in a r and omized prospect i ve study . Thymidylate synthase ( TS ) and dihydropyrimidine dehydrogenase ( DPD ) expression were investigated in resected tumors and the relationship between their expression and clinical factors in NSCLC patients was examined . PATIENTS AND METHODS Fifty-four NSCLC patients had undergone complete surgical resection and lymph node dissection , and had been administered UFT post-surgery . The TS and DPD expression in the tumor tissues was evaluated by immunohistochemical staining . The relationship between TS and /or DPD expression and clinicopathological factors was examined . RESULTS There were 38 TS-negative and 16 TS-positive cases , and 22 DPD-negative and 32 DPD-positive cases . There was no significant difference between the patients with TS or DPD and those without TS or DPD in age , gender , histological type or p-stage . The 5-year survival rates of patients positive and negative for TS were 50.0 and 89.5 % , while 10-year survival rates were 23.3 and 79.7 % , respectively ( p<0.001 ) . The 5-year survival rates of TS-positive and TS-negative patients in p-stage I were 54.6 and 95.5 % , while 10-year survival rates were 22.7 and 95.5 % , respectively ( p<0.001 ) . There was no significant difference between DPD-positive and DPD-negative patients in prognosis . CONCLUSION The oral administration of UFT after surgery might improve the survival of NSCLC patients when TS levels in tumor tissues are low . Immunohistochemical evaluation of TS and DPD expression may be useful for predicting the efficacy of UFT after complete resection in NSCLC PURPOSE We tested the hypothesis that polymerase chain reaction ( PCR ) quantitation of the enzyme thymidylate synthase ( TS ) within a primary adenocarcinoma of the stomach , has an inverse relationship to response and survival for patients who receive fluorouracil (5FU)-based chemotherapy . PATIENTS AND METHODS Before systemic chemotherapy , the genetic expression of TS ( TSmRNA level ) was determined using a PCR method . Gene expression was calculated by determining the ratio between the amount of radiolabeled PCR product with the linear amplification range of the TS gene and the beta-actin gene . Chemotherapy consisted of two cycles of protracted infusion ( PI ) 5FU 200 mg/m2/d administered for 3 weeks with leucovorin 20 mg/m2/w . Cisplatin 100 mg/m2 was administered on day 1 . RESULTS Sixty-five patients with primary gastric cancer had a median TS mRNA level of 4.6 x 10(-3 ) ( range , 0.9 to 20.1 x 10(-3 ) ) . Thirty-five percent of patients had measurable responses in their primary tumors . The mean gastric cancer TSmRNA level in responding and resistant patients is statistically significant ( P < .001 ) . The median survival time was 43 + months for treated patients with TSmRNA levels less than the median and 6 months for those with TS m-RNA levels greater than the median ( P = .003 ) . CONCLUSION The genetic expression of TS ( TSmRNA level ) influences response to 5FU-based chemotherapy and survival for a cohort of patients with primary gastric cancer . Confirmation of these data could lead to therapeutic decisions based on specific molecular properties within a tumor Human non-small cell lung carcinomas of previously untreated patients were analyzed for expression of thymidylate synthase ( TS ) using immunohistochemistry . Of the 94 tumors , 67 were positive for TS and 27 negative . A significant correlation between the expression of TS and the resistance to doxorubicin was found ( p < 0.0001 ) . Eighty-four percent of the TS-positive tumors were resistant to doxorubicin , whereas of the 27 TS-negative tumors only 44 percent were resistant . A group of patients ( n = 13 ) were treated with combination chemotherapy including 5-fluorouracil , doxorubicin and cisplatinum . Seven of the 8 tumors which were TS-positive were clinical ly progressive , whereas 4 of 5 tumors which were TS-negative showed clinical remission after chemotherapy ( p < 0.05 ; Fisher exact test ) . The patients whose tumors were TS negative lived significantly longer than those with TS-positive tumors . The median survival times were 185 weeks for patients with TS-negative and 41 weeks for patients with TS-positive tumors ( p < 0.05 ; log-rank-test ) . Thus the expression of TS is a strong prognostic factor for resistance of tumors , clinical course and survival of patients with non-small cell lung carcinomas Background : Pemetrexed has emerged as one of the most active agents for the treatment of patients with advanced non-small cell lung cancer ( NSCLC ) . We conducted a phase II study to assess the efficacy and feasibility of integrating pemetrexed in a concurrent therapy plan for patients with stage III NSCLC . Methods : Patients with stage III NSCLC with performance status 0 to 1 , adequate organ function including pulmonary function , and V20 less than 40 % were eligible . Patients were treated with cisplatin 75 mg/m2 ( first five patients 60 mg/m2 ) and pemetrexed 500 mg/m2 every 21 days for three cycles with chest radiotherapy to 66 Gy . Patients then received three cycles of docetaxel 75 mg/m2 every 21 days . Tumors were analyzed for Excision Repair Cross Complementation Group 1 and thymidylate synthase . Results : Patient characteristics ( N = 28 ) were median age , 60 ; males , 68 % ; stage IIIB , 64 % ; and squamous cell , 43 % . Twenty-four patients ( 86 % ) completed all three cycles of cisplatin/pemetrexed . Of the 24 patients eligible for docetaxel , 21 ( 87 % ) received it . Grade 3/4 toxicities were neutropenia ( 39 % ) , febrile neutropenia ( 14 % ) , esophagitis ( 14 % ) , and pneumonitis ( 4 % ) . Median survival was 34 months , and 1-year survival was 66 % . Survival was not significantly different in squamous and other histology patients . Tumor analysis in 16 patients showed that moderate/strong expression of thymidylate synthase was significantly associated with progression-free survival and overall survival . Conclusion : Integrating pemetrexed in a concurrent therapy regimen for patients with stage III NSCLC is feasible and was associated with a median survival of 34 months |
12,122 | 24,660,187 | Staged and simultaneous augmentation procedures in the anterior maxilla are both associated with high implant success and survival rates .
The level of evidence , however , is better for the staged approach than for the simultaneous one | PURPOSE To systematic ally review clinical studies examining the survival and success rates of implants in horizontal ridge augmentation , either prior to or in conjunction with implant placement in the anterior maxilla . | This study describes a new surgical technique for harvesting intra-membranous bone from the m and ibular symphyseal region and using it as an inlay graft . The surgical technique of turning a complex-shaped defect into a defect of defined size by contour preparation and insertion of an appropriate inlay graft was used in 31 patients . At 4 months , 15 patients ( 48 % ) showed negligible graft resorption of 0.33 mm . At 5 - 8 months the resorption rate in the remaining 16 patients was around 1.22 mm . All in all , a significant positive correlation was found between bone resorption and time ( r = 0.574 ; P < 0.001 ) . All patients received an implant after the fixation screw was removed . A conservative interpretation of the results suggests that , on account of the flush fit and the early revascularization of the graft , implants may and should , in fact , be inserted earlier in order to prevent graft resorption OBJECTIVES To evaluate healing of marginal defects in immediate transmucosal implants grafted with anorganic bovine bone , and to assess mucosal and radiographic outcomes 3 - 4 years following restoration . MATERIAL AND METHODS Thirty immediate transmucosal implants in maxillary anterior extraction sites of 30 patients r and omly received BioOss ( N=10 ; BG ) , BioOss and resorbable collagen membrane ( N=10 ; BG+M ) or no graft ( N=10 ; control ) . RESULTS Vertical defect height ( VDH ) reductions of 81.2+/-5 % , 70.5+/-17.4 % and 68.2+/-16.6 % , and horizontal defect depth ( HDD ) reductions of 71.7+/-34.3 % , 81.7+/-33.7 % and 55+/-28.4 % were observed for BG , BG+M and control groups , respectively , with no significant inter-group differences . Horizontal resorption was significantly greater in control group ( 48.3+/-9.5 % ) when compared with BG ( 15.8+/-16.9 % ) and BG+M ( 20+/-21.9 % ) groups ( P=0.000 ) . Ten sites ( 33.3 % ) exhibited recession of the mucosa after 6 months ; eight ( 26.7 % ) had an unsatisfactory esthetic result post-restoration due to recession . Mucosal recession was significantly associated ( P=0.032 ) with buccally positioned implants ( HDD 1.1+/-0.3 mm ) when compared with lingually positioned implants ( HDD 2.3+/-0.6 mm ) . In 19 patients followed for a mean of 4.0+/-0.7 years , marginal mucosa and bone levels remained stable following restoration . CONCLUSION BioOss significantly reduced horizontal resorption of buccal bone . There is a risk of mucosal recession and adverse soft tissue esthetics with immediate implant placement . However , this risk may be reduced by avoiding a buccal position of the implant in the extraction socket Two techniques of ridge augmentation using onlay bone graft alone or associated with a non-resorbable membrane have been previously described . This prospect i ve , r and omized study compared these two techniques at 6 months , in terms of bone gain , resorption and quality obtained at edentulous sites . Osseous measurements were taken using stents , callipers and CT-scans . Membrane exposure occurred at one site , 4 weeks after placement . Endosseous implants were successfully placed at all grafted sites . The mean graft thickness for all subjects was 4.7 mm ( range : 2.3 - 6.2 mm ) . Overall mean resorption was 1.5 mm ( range : 0 - 4.6 mm ) whereas overall mean width gain was 3.2 mm ( range : 0.8 - 6.2 mm ) . Six months following surgery , the membrane group experienced significantly less bone resorption than the graft alone group ( P<0.01 ) . Width augmentation did not differ significantly between the two groups . In conclusion , combining a membrane with an onlay graft demonstrates less bone resorption with a minimal risk of complications . Longer follow-up is needed to confirm the benefits of using a non-resorbable membrane BACKGROUND Early implant placement is one of the treatment options after tooth extraction . Implant surgery is performed after a healing period of 4 to 8 weeks and combined with a simultaneous contour augmentation using the guided bone regeneration technique to rebuild stable esthetic facial hard- and soft-tissue contours . METHODS In this prospect i ve study , 20 patients were treated with an implant-born single crown and followed for 3 years . Clinical , radiologic , and esthetic parameters were recorded to assess treatment outcomes . RESULTS At the 3-year examination , all 20 implants were successfully integrated , demonstrating ankylotic stability and healthy peri-implant soft tissues as documented by st and ard clinical parameters . Esthetic outcomes were assessed by the pink esthetic score ( PES ) and white esthetic score ( WES ) and confirmed pleasing results overall . WES values were slightly superior to PES values . Periapical radiographs showed minimal crestal bone loss around used bone-level implants with a mean bone loss of 0.18 mm at 3 years . Only two implants revealed bone loss between 0.5 and 1.0 mm . One of these implants had minor mucosal recession < 1.0 mm . CONCLUSIONS This prospect i ve study evaluates the concept of early implant placement and demonstrated successful tissue integration for all 20 implants and stable bone-crest levels around implant-abutment interfaces according to the platform-switching concept . The midterm 3-year follow-up revealed pleasing esthetic outcomes and stable facial soft tissues . The risk of mucosal recession was low , with only one patient showing minor recession of the facial mucosa . These encouraging results need to be confirmed with a 5-year follow-up examination Bone grafting may be required prior to implant placement , at the time of implant placement , or subsequent to it . The aim of this study was to compare the healing of onlay block grafts when deproteinized bovine bone coverage was used with the healing of the grafts without such coverage . The purpose was a clinical evaluation of deproteinized bovine bone 's ability to reduce grafted bone resorption . The results indicated that bovine bone can be placed over grafted areas , taking advantage of its osteoconductive properties and compensating for the natural bone resorption caused by remodeling OBJECTIVES Autologous bone augmentation to rebuild compromised alveolar ridge contour prior to implant placement allows for favorable three-dimensional implant positioning to achieve optimum implant esthetics . The aim of the present study was to evaluate peri-implant soft tissue conditions around single-tooth implants following bone grafts in the esthetic zone of the maxilla . MATERIAL S AND METHODS Sixty patients underwent autologous bone augmentation of deficient maxillary sites prior to placement of 85 implants in the esthetic zone . In case of multiple implants per patient , one implant was r and omly selected . Objective evaluation of 60 single-tooth implants was performed using the Pink-Esthetic-Score ( PES ) and Papilla Index ( PI ) and supplemented by subjective patient evaluation , as well as clinical and radiologic examination . RESULTS Objective ratings of implant esthetics were satisfactory ( median PES : 11 , median PI : 2 ) and significantly correlated with high patient satisfaction ( mean VAS score : 80 % ) . Both esthetic indices demonstrated respectable levels of inter- as well as intra-observer agreement . Poor implant esthetics ( low PES and PI ratings ) were significantly associated with increased anatomic crown height , while no influence of horizontal implant-tooth distance could be found . CONCLUSIONS The present investigation indicates that favorable esthetic results may be achieved in the augmented anterior maxilla . However , bony reconstruction of compromised alveolar ridges does not guarantee optimum implant esthetics The purpose of this study was to evaluate the feasibility of using a bioactive alloplast and a physical barrier to augment localized alveolar ridge defects for the subsequent placement of dental implants . Twelve systemically healthy patients ( aged 29 to 55 years ) with inadequate dental alveolar ridge widths were selected for study . All patients completed initial therapy , which included scaling , root planing , and oral hygiene instruction . All ridge defects were augmented with a bioactive glass alloplast and a titanium-reinforced e-PTFE barrier . Vertical ( height ) and horizontal ( width ) hard tissue measurements were taken the day of ridge augmentation surgery ( baseline ) and at the 6-month reentry surgery . The change in ridge width varied from a loss of 1 mm to a gain of 4.5 mm , with a mean gain of 1.1 mm ( P < .03 ) . Eight of the 12 sites gained 1 mm or less . The difference in mean ridge width gain between maxillary and m and ibular sites was not statistically significant ( P > .08 ) . Mean ridge width gain was 1.1 mm for both maxillary and m and ibular sites . There was a loss in bone height of 0.3 mm from baseline . Four implants in four patients could not be placed because of inadequate ridge width augmentation . Histologic examination of the grafted sites revealed connective tissue encapsulation of most residual graft particles . In this study , bioactive glass particulate and an e-PTFE barrier did not consistently augment localized ridge defects for dental implant placement The aim of this study was to evaluate the efficacy of allogeneic block grafts impregnated with autologous bone marrow in horizontal ridge augmentation therapy . Ten patients with severe ridge volume deficiency in the anterior maxilla were treated with horizontal ridge augmentation . The patients were r and omized into two groups : Five patients , using two allogeneic block grafts , were in the control group , and five patients , using two allogeneic block grafts impregnated with autologous bone marrow , were in the test group . Hematologists collected 4 mL of bone marrow from the iliac crest of the patients in the test group immediately prior to the surgeries . The blocks were fixed using titanium screws to obtain rigid fixation and to st and ardize the reference points for measurement purpose s. CT scans were obtained both preoperatively and six months postoperatively to allow evaluation of horizontal bone gain . After a healing period of six months , the sites were reopened and the screws were removed . Before implant placement , bone cores were harvested and prepared for histologic and histomorphometric evaluation . Tomographic and histomorphometric measurements were recorded . The test group demonstrated better tomographic results ( P < 0.05 ) in augmenting alveolar thickness , with a mean value of 4.60 ± 1.43 mm ( 118.23 ± 56.93 % ) , while the control group had bone gain of 2.15 ± 0.47 mm ( 49.91 ± 20.24 % ) . Despite the different results in alveolar thickness gained between groups , all sites received dental implants . The histomorphometric analysis also showed better results ( P < 0.05 ) in the amount of vital mineralized bone in the test group as compared to the control group . The findings of this study suggest that an autologous bone marrow aspirate can increase the regenerative potential of corticocancellous allogeneic bone grafts A classification of the edentulous jaws has been developed based on a r and omised cross-sectional study from a sample of 300 dried skulls . It was noted that whilst the shape of the basalar process of the m and ible and maxilla remains relatively stable , changes in shape of the alveolar process is highly significant in both the vertical and horizontal axes . In general , the changes of shape of the alveolar process follows a predictable pattern . Such a classification serves to simplify description of the residual ridge and thereby assist communication between clinicians ; aid selection of the appropriate surgical prosthodontic technique ; offer an objective baseline from which to evaluate and compare different treatment methods ; and help in deciding on interceptive techniques to preserve the alveolar process . An awareness of the pattern of resorption that takes place in various parts of the edentulous jaws , enables clinicians to anticipate and avert future problems BACKGROUND Various causes of facial bone loss around dental implants are reported in the literature ; however , reports on the influence of residual facial bone thickness on the facial bone response ( loss or gain ) have not been published . This study measured changes in vertical dimension of facial bone between implant insertion and uncovering and compared these changes to facial bone thickness for more than 3,000 hydroxyapatite (HA)-coated and non-HA-coated root-form dental implants . METHODS Subjects were predominantly white males , 18 to 80 + years of age ( mean 62.9 years ) , who were patients at 30 Department of Veterans Affairs Medical Centers and two university dental clinics . Alveolar ridges ranged from normal to resorbed with intact basal bone . Following preparation of the osteotomy site , direct measurements with calipers were made of the residual facial bone thickness , approximately 0.5 mm below the crest of the bone . The distance from the top of the implants to the crest of the facial bone was also measured using periodontal probes . Implants were uncovered between 3 to 4 months in the m and ible and 6 to 8 months in the maxilla after insertion . Facial bone response was the difference between the height of facial bone at Stage 1 ( insertion ) and Stage 2 ( uncovering ) . RESULTS The mean facial bone thickness after osteotomies were made was 1.7 + /- 1.13 mm . When a mean facial bone thickness of 1.8 + /- 1.41 mm or larger remained after site preparation , bone apposition was more likely to occur . The mean facial bone response for 2,685 implants was -0.7 + /- 1.70 mm . For implants integrated at uncovering , the mean bone response was -0.7 + /- 1.69 mm , and -2.8 + /- 1.57 mm for implants mobile at uncovering . Bone quality -4 had the least facial bone response , -0.5 + /- 2.11 mm . Bone responses were similar for both HA-coated and non-HA-coated implants . CONCLUSIONS Significantly greater amounts of facial bone loss were associated with implants that failed to integrate . As the bone thickness approached 1.8 to 2 mm , bone loss decreased significantly and some evidence of bone gain was seen . There was no statistically or clinical ly significant difference in bone response between HA-coated and non-HA-coated implants OBJECTIVES To assess in a r and omized- clinical trial the influence of three augmentation techniques ( chinbone with or without a Bio-Gide membrane and Bio-Oss with a Bio-Gide membrane ) on the clinical and radiographic characteristics of hard and soft tissues around implants and adjacent teeth in the reconstructed maxillary anterior region , up to 1 year after functional loading . MATERIAL S AND METHODS Ninety-three patients requesting single-tooth replacement and presenting with a horizontal ( bucco-palatinal ) bone deficiency were included . After augmentation , 93 ITI-Esthetic(Plus ) implants were placed . Clinical variables , st and ardized photographs and radiographs were analysed to assess the impact on the levels of the marginal gingiva ( MGL ) and marginal bone ( MBL ) around implants and adjacent teeth , viz at pre-augmentation , pre-implantation ( TPI ) and 1 ( T(1 ) ) and 12 ( T(12 ) ) months after final crown placement . RESULTS Implant survival was 97.8 % . No significant differences were observed in the treatment outcomes of the three augmentation modalities . Combining the three modalities , a slight but significant increase in the implants approximal pocket depth was found between T(1 ) and T(12 ) . Approximal bone loss at the implant between T(1 ) and T(12 ) was 0.14 + /- 0.76 mm ( mesial ) and 0.14 + /- 0.47 mm ( distal ) ; the approximal MGL slightly increased ( mesial : 0.24 + /- 0.46 mm , distal : 0.25 + /- 0.66 mm ) , and the buccal MGL decreased ( 0.11 + /- 0.61 mm ) . Bone loss at the adjacent teeth , although minor , was significant between TPI and T(1 ) . No correlations were observed in changes of MBL and MGL . CONCLUSIONS None of the three applied augmentation technique procedures influenced the characteristics of the MGL and MBL or the implant survival of single-tooth replacements . Peri-implant hard and soft tissues were very stable in the first year after loading The aim of this study was to analyse the clinical outcome of two different surgical methods for the reconstruction of narrow edentulous ridges before implant installation : guided bone regeneration with e-PTFE membranes and autologous bone chips or grafting of autologous bone blocks without e-PTFE membranes . Thirty partially edentulous patients , presenting insufficient bone width ( less than 4 mm ) in the edentulous sites for installation of screw-type titanium implants , were selected and assigned to two different treatment modalities . Fifteen patients ( group 1 ) were treated by means of guided bone regeneration with e-PTFE membranes supported by stainless steel screws and autologous bone chips taken from intraoral sites . Fifteen patients ( group 2 ) were treated by means of autologous bone blocks taken from intraoral or extraoral sites ( anterior iliac crest and calvaria ) and stabilized with titanium microscrews . Six to 8 months later , during re-entry for implant insertion , the gain of ridge width obtained was measured . In group 1 the average amount of bone gain was 2.7 mm , whereas in group 2 the value was 4.0 mm . Five to 6 months after implant placement prosthetic rehabilitation was started . The mean follow-up after prosthetic load has been 22.4 months . Success rates of implants according to Albrektsson criteria has been 93.3 % in group 1 , and 90.9 % in group 2 . Although a statistical comparison between the two treatment modalities may not be feasible , due to the bias result ing from the choice of treatment by the clinician and from the differences in donor sites and defect extension , some considerations can be made : 1 ) both methods are a reliable means for the correction of narrow edentulous ridges ; 2 ) both techniques necessitate overcorrection of the defect because of interposition of connective tissue beneath the membrane in the first group and bone resorption in the second one ; 3 ) the use of semipermeable barriers increases the costs of the surgical procedure , as compared to bone grafting without membranes ; 4 ) guided bone regeneration presents a higher risk of infection because of wound dehiscence and membrane exposure . Therefore , in case of wide edentulous areas , reconstruction of narrow ridges should be performed with bone blocks without membranes OBJECTIVES the aim of the present study was to evaluate the dimensional changes of peri-implant tissues obtained by implant placement , bone and soft tissue augmentation , prosthetic reconstruction and 1 year of function using a new , non-invasive method for volumetric measurements . MATERIAL S AND METHODS in 16 patients , the missing central or lateral maxillary incisor was reconstructed with an implant-supported single crown . Impressions were taken before ( t1 ) , after implant placement with guided bone regeneration using DBBM and a PTFE membrane ( t2 ) , after soft tissue augmentation ( t3 ) , immediately after crown placement ( t4 ) and 1 year later ( t5 ) . The cast models were optically scanned and digitally superimposed allowing qualitative and quantitative analysis of alterations of the labial peri-implant tissue contour . In addition , the crown length and papilla height were measured at crown placement ( t4 ) and after 1 year ( t5 ) . RESULTS fifteen patients were available for recall after 1 year . During therapy , a mean gain in distance in the labial direction of 1.27 ± 0.67 mm was observed after the surgical procedures . One year after crown insertion , a mean loss of 0.04 ± 0.31 mm in the labial direction was recorded . During the same period , the crown length increased by a mean of 0.22 ± 0.57 mm and the papilla height by 0.07 ± 0.61 mm . The degree and pattern of tissue change following crown insertion were highly variable between individuals , irrespective of the amount and quality of previously augmented tissues . CONCLUSIONS the clinical procedures were effective in augmenting peri-implant tissue volume that remained stable to a high degree within 1 year after crown insertion . Large inter-individual variations regarding the tissue alterations were observed |
12,123 | 31,892,984 | Conclusions : Significant correlations were revealed among prostatitis , BPH and PCa .
Prostatitis or BPH could lead to escalating risks of PCa .
Meanwhile , people with a history of prostatitis might be more vulnerable to BPH | Background : No consensus has been reached on the definite associations among prostatitis , benign prostatic hyperplasia ( BPH ) and prostate cancer ( PCa ) .
Hence , this meta- analysis was conducted to explore their triadic relation by summarizing epidemiological evidence . | A case-control study was conducted within Group Health Cooperative of Puget Sound to evaluate the relation between prior vasectomy and the risk of prostate cancer . Cases consisted of 175 men newly diagnosed with histologically confirmed prostate cancer during 1989 - 1991 . A total of 258 controls , matched to cases on birth year and membership status , were r and omly selected from the general membership of the plan . Information was collected from mailed question naires and medical records on medical history , including prior vasectomy , anthropometric measures , family history of prostate cancer , personal habits , and medical care utilization , and demographic factors . Conditional logistic regression analyses showed that the odds ratio for prostate cancer associated with vasectomy was 0.86 ( 95 % confidence interval 0.57 - 1.32 ) after adjustment for confounders . The odds ratio estimate did not differ substantially by age at vasectomy or time since vasectomy . However , the odds ratio estimate for prostate cancer associated with vasectomy tended to be increased among men who had a father or brother with prostate cancer . Nevertheless , the increased risk may be related to detection bias or differential participation rates due to both vasectomy status and a family history of prostate cancer . These results suggest no overall association between vasectomy and prostate cancer OBJECTIVES CP/CPPS is a commonly observed distress in male patients . Because of its little-known etiology , no effective therapy has been developed which has promising outcomes . Therefore , there is a need to develop a valid model which can mimic the etiology of CP/CPPS . MATERIAL S AND METHODS Fifty male C57BL/6 mice were r and omly and averagely divided into 5 groups of 10 mice each . The control group was injected with 0.9 % NaCl solution . Aluminum hydroxide and T2 groups were injected with aluminum hydroxide adjuvant and T2 peptide . T2 plus complete Freund adjuvant ( CFA ) with aluminum hydroxide group was injected with a mixture of T2 , CFA and aluminum hydroxide adjuvant . At the same time , CFA group was injected with complete Freund adjuvant . Hematoxylin-eosin stain and immunohistochemistry were used to investigate inflammatory lesion and expression of IL-β1 . Furthermore , TNF-α and CRP protein levels were evaluated by using commercially available ELISA kits . The ANOVA test was used to compare the statistical differences among groups . RESULTS Prostates from a mixture of T2 plus CFA with aluminum hydroxide immunized mice showed elevated lesions and high level of inflammatory cells infiltration compared to the other groups . In addition , the levels of TNF-α , IL-β1 , and CRP were also higher in the T2 plus CFA with aluminum hydroxide group as compared to the other groups . CONCLUSION Our results showed that T2 with CFA plus aluminum hydroxide adjuvant injection could successfully induce CP/CPPS in mice . This autoimmune novel model provides a useful , economic , safer , and easy tool for exploring the etiology and pathophysiology of CP/CPPS which will improve the therapeutic outcomes PURPOSE Black men are diagnosed with prostate cancer more often than white men , present with more advanced disease and have worse stage specific survival . Given the high risk of incidence and mortality in this population , determining potentially modifiable factors is important . Recent studies have suggested a link between chronic inflammation and development of prostate cancer . In concurrence , population based studies of white men have revealed an increased risk of prostate cancer with history of sexually transmitted diseases and prostatitis . MATERIAL S AND METHODS We explored the chronic inflammation hypothesis of prostate cancer development among black men by examining sexual activity , sexually transmitted diseases and prostatitis in a population based study of 129 patients and 703 controls 40 to 79 years old . RESULTS After adjusting for age , income , cigarette smoking , and history of digital rectal examination and prostate specific antigen tests in the last 5 years , we observed that a history of gonorrhea infection and prostatitis increased the odds of prostate cancer 1.78-fold ( 95 % CI 1.13 , 2.79 ) and 4.93-fold ( 95 % CI 2.79 , 8.74 ) , respectively . Men reporting 25 or more sexual partners were 2.80 ( 95 % CI 1.29 , 6.09 ) times more likely to be diagnosed with cancer compared to men with 5 or fewer partners . CONCLUSIONS Our findings support the significance of prior sexual practice s , exposure to sexually transmitted microbial agents and history of prostatic infection in the natural history of prostate cancer in black men . Additional prospect i ve research incorporating serological markers of infectious agents or predictive markers of chronic inflammation should serve to eluci date the possible causal pathway of recurring or persistent infection in the etiology of prostate cancer in black men Background Prostatitis and sexually transmitted diseases ( STDs ) have been positively associated with prostate cancer in previous case-control studies . However , results from recent prospect i ve studies have been inconclusive . Method ogy/Principal Findings We investigated the association between prostatitis , STDs , and prostate cancer among African American , Asian American , Latino , and White participants of the California Men 's Health Study . Our analysis included 68,675 men , who completed a detailed baseline question naire in 2002–2003 . We identified 1,658 incident prostate cancer cases during the follow-up period to June 30 , 2006 . Cox proportional hazards models were used to estimate relative risks and 95 % confidence intervals . Overall , men having a history of prostatitis had an increased risk of prostate cancer than men with no history ( RR = 1.30 ; 95 % CI : 1.10–1.54 ) . Longer duration of prostatitis symptoms was also associated with an increased risk of prostate cancer ( P trend = 0.003 ) . In addition , among men screened for prostate cancer ( 1 or 2 PSA tests ) , a non-significant positive association was observed between prostatitis and prostate cancer ( RR = 1.10 ; 95 % CI : 0.75–1.63 ) . STDs were not associated with overall prostate cancer risk . In racial/ethnic stratified analysis , Latinos reporting any STDs had an increased risk of disease than those with no STDs ( RR = 1.43 ; 95 % CI : 1.07–1.91 ) . Interestingly , foreign-born Latinos displayed a larger risk associated with STDs ( RR = 1.87 ; 95 % CI : 1.16–3.02 ) than U.S. born Latinos ( RR = 1.15 ; 95 % CI : 0.76–3.02 ) . Conclusion In summary , results from this prospect i ve study suggest that prostatitis and STDs may be involved in prostate cancer susceptibility . While we can not rule out the possible influence of incidental detection , future studies are warranted to further investigate the role of infectious agents related to prostatitis and STDs in prostate cancer development Background : The incidence of prostate cancer is much lower in Asian men than in Western men . This study investigated whether prostate cancer is associated with prostatitis , benign prostatic hyperplasia ( BPH ) , and other medical conditions in the low-incidence population . Methods : From the cl aims data obtained from the universal National Health Insurance of Taiwan , we identified 1184 patients with prostate cancer diagnosed from 1997 to 2008 . Controls comprised 4736 men r and omly selected from a cancer-free population . Both groups were 50 years of age or above . Medical histories between the two groups were compared . Results : Multivariate logistic regression analysis showed that prostatitis and BPH had stronger association with prostate cancer than the other medical conditions tested . Compared with men without prostatitis and BPH , a higher odds ratio ( OR ) for prostate cancer was associated with BPH ( 26.2 , 95 % confidence interval ( CI ) 20.8–33.0 ) than with prostatitis ( 10.5 , 95 % CI=3.36–32.7 ) . Men with both conditions had an OR of 49.2 ( 95 % CI=34.7–69.9 ) . Conclusion : Men with prostate cancer have strong association with prostatitis and /or BPH . Prostatitis interacts with BPH , result ing in higher estimated relative risk of prostate cancer in men suffering from both conditions AIMS Interstitial cystitis/bladder pain syndrome ( IC/BPS ) is a prevalent disorder that may contribute to bladder cancer ( BC ) . This cohort study set out to investigate the association between IC/BPS and BC by using a population -based data set . METHODS The data for this study were source d from the Taiwan National Health Insurance program . The case cohort comprised 7,562 patients with IC/BPS , and 22,686 r and omly selected subjects were used as a comparison cohort . A Cox proportional hazards regression model ( stratified by age group , geographic location , urbanization level , and the index year ) was constructed to estimate the risk of subsequent BC following a diagnosis of IC/BPS . We also ran the analysis utilizing an alternative comparison cohort composed of patients with urinary incontinence ( UI ) . RESULTS In the study sample of 30,248 patients , 96 patients ( 0.32 % ) received a diagnosis of BC during the 3-year follow-up period ; 48 ( 0.63 % of patients with IC/BPS ) were from the study cohort ; and 48 ( 0.21 % of patients without IC/BPS ) were from the comparison cohort . The incidence rate of BC was 2.12 ( 95 % CI : 1.58 - 2.78 ) per 1,000 person-years in patients with IC/BPS and 0.70 ( 95 % CI : 0.52 - 0.92 ) per 1,000 person-years in comparison patients . Cox proportional analysis revealed that the adjusted HR for BC during the 3-year follow-up period for patients with IC/BPS was 2.95 ( 95 % CI : 1.97 - 4.41 ) that of comparison subjects . When performing the analysis with the alternative UI comparison cohort , the adjusted HR for BC was 1.96 ( 95 % CI : 1.14 - 3.39 ) . CONCLUSIONS This investigation detected a novel association between BC and prior IC/BPS A population -based case-control study of prostate cancer was performed in King County , Washington , in White men and Black men aged 40 - 64 years , between 1993 and 1996 . Incident prostate cancer cases ( n = 753 ) were identified from the Seattle-Puget Sound Surveillance , Epidemiology , and End Results ( SEER ) cancer registry . Controls ( n = 703 ) were identified through r and om digit dialing and were frequency matched to cases on age . Sexual behavior , medical history , and other potential prostate cancer risk factors were ascertained through an in-person interview . There was no relation between sexual orientation and prostate cancer , although the number of men who had sex with men was small . Risk estimates increased directly with the lifetime number of female sexual partners ( trend p < 0.001 ) but not with male partners ( trend p = 0.62 ) . Risk also increased with decreasing age at first intercourse , but this effect disappeared after adjusting for the number of female partners . Prior infection with gonorrhea was positively associated with risk ( odds ratio = 1.50 ; 95 % confidence interval : 1.0 , 2.2 ) , but no effect was seen among men with other sexually transmitted diseases . No relation between lifetime frequency of sexual intercourse and risk of prostate cancer was apparent . These findings are consistent with previous studies that support an infectious etiology for prostate cancer OBJECTIVES To determine the risk factors for the self-reported history of prostatitis and to determine whether a self-reported history of prostatitis is related to the diagnosis of prostate cancer . METHODS R and om digit dialing was used to select a group of controls aged 40 to 64 years without prostate cancer matched by age with a group of patients with prostate cancer in a study on the epidemiology of prostate cancer . Controls were divided into those who reported a diagnosis of prostatitis ( cases ) and those who denied ever having had prostatitis ( controls ) . We adjusted for the time from a prostatitis diagnosis to the in-person interview . We also compared the number of men with a prostatitis diagnosis to the number of men diagnosed and not diagnosed with prostate cancer . RESULTS Of the 645 control men without a history of prostate cancer , 58 ( 9.0 % ) reported a diagnosis of prostatitis . The men with prostatitis had a mean age of 39.5 years at diagnosis . The urinary symptoms among prostatitis cases and controls was similar . Prostatitis cases more frequently reported urinary ( P < or = 0.05 ) or urethral infections ( P < or = 0.01 ) before diagnosis . Men with prostatitis were more likely to have procedures aim ed at diagnosing both prostatic and other diseases . Men with prostate cancer reported a diagnosis of prostatitis more often than the noncancer controls ( 13.6 % versus 9.0 % ) . After controlling for the number of prostate-specific antigen tests this difference disappeared . CONCLUSIONS Nine percent of a r and omly selected group of middle-aged men reported they had been diagnosed with prostatitis . The prevalence of a prostatitis diagnosis is similar in men with and without prostate cancer Background : Sexually transmissible infections ( STI ) have been variably associated with increased risks of prostate cancer , largely in case-control studies . Methods : In the Prostate , Lung , Colorectal , and Ovarian Cancer Screening Trial , we examined risk of prostate cancer in relation to serum antibodies to Chlamydia trachomatis , human papillomavirus-16 and -18 , herpes simplex virus-2 , cytomegalovirus , and human herpesvirus-8 in 868 cases ( 765 Whites and 103 Blacks ) and 1,283 controls matched by race , age , time since initial screening , and year of blood draw ; all blood sample s were collected at least 1 year before prostate cancer diagnosis , except for 43 Black cases . We also assessed risk associated with self-reported history of syphilis and gonorrhea . Results : Prevalences of the 7 STIs among controls were weakly correlated , and all were more frequent among Blacks than Whites , except for human herpesvirus-8 . Among Whites , prostate cancer risk was not significantly associated with the individual infections or with their number ( Ptrend = 0.1 ) ; however , men with one or more STI had slightly higher risk ( odds ratio , 1.3 ; 95 % confidence interval , 1.0 - 1.6 ) . Among Blacks , excess risk was associated with IgA antibody to C. trachomatis ( odds ratio , 2.1 ; 95 % confidence interval , 1.2 - 3.6 ) . Conclusion : This large prospect i ve study of prostate cancer shows no consistent association with specific STIs and a borderline association with any versus none . Whether a shared response or correlated infection not directly measured underlies the weak association requires further study . ( Cancer Epidemiol Biomarkers Prev 2008;17(9):2374–81 Objectives Prostate cancer has few known risk factors . As part of a population -based case – control study conducted in four health maintenance organizations , the authors examined the associations between fatal prostate cancer and several medical and behavioral characteristics . Methods Cases were 768 health plan members who died of prostate adenocarcinoma during the period 1997–2001 . We r and omly selected controls ( 929 ) from the health plan membership and matched them to cases on health plan , age , race , and pattern of health plan membership . We examined medical records to obtain information on potential risk factors during the 10 years before the date on which prostate cancer was first suspected ; the same reference date was used for the matched controls . Results Anthropometric characteristics , as well as personal histories of benign prostatic hypertrophy , transurethral prostatectomy , cancer , diabetes , prostatitis , hypertension , and vasectomy were largely similar for cases and controls . Men who died from prostate cancer were more likely than controls to have been cigarette smokers according to the most recent smoking notation before the reference date ( odds ratio 1.5 , 95 % confidence interval 1.1–2.0 ) . Conclusions The observed increase in risk associated with recent cigarette smoking is consistent with the findings of several other studies . However , in contrast with some reports , we observed no connection between fatal prostate cancer and some prior health conditions or measures of body size Alcohol consumption and cigarette smoking have been suggested as possible causes of prostate cancer . We therefore examined this relation in a cohort of 43,432 men who were members of a prepaid health plan in northern California ( United States ) and who had received a health examination in the period from 1979 through 1985 . Detailed information on demographic variables , alcohol consumption , smoking habits , medical complaints and conditions , occupation , and surgery ( including vasectomy ) was assessed . Symptoms of prostatism and a history of sexually transmitted diseases were abstract ed from the medical records of all prostate cancer patients and of a matched sub sample of r and omly selected control-subjects . Alcohol consumption was associated with no elevated prostate cancer risk for the 238 men in our study in whom prostate cancer developed , but smoking one or more packs of cigarettes per day was associated with an adjusted relative risk ( RR ) of 1.9 ( 95 percent confidence interval [CI]=1.2–3.1 ) . Prostate cancer risk for Black men was 2.2 ( CI=1.6–3.1 ) when compared with that for White men , and education level was associated positively in an increasing trend ( P<0.02 ) up to an RR of 1.4 ( CI=0.9–2.1 ) among men with postgraduate education . Symptoms of prostate hypertrophy were not associated with elevated risk of prostate cancer if they occurred two or more years before the diagnosis . The finding that smoking increased the risk of prostate cancer confirms the observations of others but needs cautious interpretation because we were unable to adjust for the potential confounding effect of dietary and hormonal factors AIM To examine the diagnosis and treatment of chronic prostatitis by means of a nationwide postal survey of practicing urologists in 2004 . METHODS A r and om sample of 850 Korean urologists from the Korean Urological Association Registry of Physicians were asked to complete a question naire that explored practicing characteristics , attitudes and diagnostic and treatment strategies in the management of chronic prostatitis . RESULTS Of the 850 question naires sent , 302 were returned ( response rate 35.5 % ) and 275 were induced in the final analysis . More than 50 % believed in a multifactorial etiology for chronic prostatitis and 52 % considered chronic abacterial prostatitis to be bacterial in nature . For routine diagnostic assessment , the most commonly used tests were reported to be urinalysis ( 95.3 % ) , analysis of expressed prostatic secretions ( 89.5 % ) and digital rectal examination ( 81.1 % ) . Only a few urologists use specific lower urinary tract cultures . Symptom assessment according to the National Institute of Health-Chronic Prostatitis Symptom Index was less frequently used ( 12.7 % ) . First choices for therapy included antibiotics ( 96.4 % ) , alpha-blockers ( 71.6 % ) and sitz baths ( 70.5 % ) . If unsuccessful , urologists frequently continued to prescribe a second course of either alpha-blockers ( 69.5 % ) or antibiotics ( 57.8 % ) . CONCLUSION These data provide a picture of current practice regarding the management of chronic prostatitis in Korea . The diagnostic and treatment practice s for prostatitis do not follow st and ard textbook algorithms . Further studies are needed to eluci date the etiology and pathogenesis of chronic prostatitis and to establish guidelines for its diagnosis and treatment PURPOSE We used a national data base to explore the epidemiology of physician visits for genitourinary symptoms or a diagnosis of prostatitis . MATERIAL S AND METHODS We analyzed 58,955 visits by men 18 years old or older to office based physicians of all specialties , as included in the National Ambulatory Medical Care Surveys from 1990 to 1994 . Physicians selected by r and om sampling completed visit forms that included information on patient reasons for visits and physician diagnoses . RESULTS From 1990 to 1994 , 5 % of all ambulatory visits by men 18 years old or older included genitourinary symptoms as a reason for the visit . In almost 2 million visits annually prostatitis was listed as a diagnosis , including 0.7 million by men 18 to 50 years old and 0.9 million by those older than 50 years . Of the prostatitis visits 46 and 47 % were to urologists and primary care physicians , respectively . A prostatitis diagnosis was assigned at 8 and 1 % of all urologist and primary care physician visits , respectively . The odds of a prostatitis diagnosis were 13-fold greater at visits to urologists compared with visits to primary care physicians , and approximately 2-fold greater in the south than in the northeast . Surprisingly , compared with men 66 years old or older , prostatitis was more commonly diagnosed in men 36 to 65 than men 18 to 35 years old . When a prostatitis diagnosis was given , antimicrobial use was likely to be reported 45 % of the time for men with and 27 % for those without genitourinary symptoms . Visits to primary care physicians were more often associated with antimicrobial use than visits to urologists . CONCLUSIONS Genitourinary symptoms are a frequent reason for office visits by younger and older men , and prostatitis is a common diagnosis . Despite a report that less than 10 % of prostatitis cases are bacterial , a much higher proportion of men in whom prostatitis is diagnosed receive antimicrobials The Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial r and omized men to usual care or annual prostate-specific antigen ( PSA ) screening for 6 yr and digital rectal examination for 4 yr . This trial found no difference between the intervention and usual care arms of the study in the primary end point of prostate cancer (PCa)-specific mortality . The PLCO trial results have had a major impact on health policy and the rate of PSA screening in the United States . We analyzed the 13-yr screening and outcomes data from the 151 participants who died of PCa in the screening arm of the trial to better underst and how r and omization to screening failed to prevent PCa death in these men . We found that of these men , 81 ( 53.6 % ) either were never screened as part of the trial or had an initial positive screen . Only 17 ( 11.3 % ) of those who died reached year 6 of the trial with a PSA < 4.0 ng/ml . The men who died in the screening arm were also older at study entry than the average PLCO participant ( 66 vs 62 yr ; p < 0.001 ) . Our analysis should inform the interpretation of the PLCO trial and provide insight into future trial design Background : Although previous case-control studies have observed positive associations among gonorrhea , syphilis , clinical prostatitis , and prostate cancer , many may have been susceptible to recall and interviewer biases due to their retrospective design s. Therefore , to investigate these associations without concerns of recall and interviewer biases , we conducted a large , prospect i ve investigation in the Health Professionals Follow-up Study . Methods : In 1992 , participants were asked to report their histories of gonorrhea , syphilis , and clinical prostatitis by mailed question naire . Prostate cancer diagnoses were ascertained by self-report on the 1994 and each subsequent biennial follow-up question naire and confirmed by medical record review . Results : Of the 36,033 participants in this analysis , 2,263 were diagnosed with prostate cancer between the date of return of the 1992 question naire and 2002 . No association was observed between gonorrhea [ adjusted relative risk ( RR ) , 1.04 ; 95 % confidence interval ( 95 % CI ) , 0.79 - 1.36 ] or syphilis ( RR , 1.06 ; 95 % CI , 0.44 - 2.59 ) and prostate cancer . Overall null results were also observed between clinical prostatitis and prostate cancer ( RR , 1.08 ; 95 % CI , 0.96 - 1.20 ) , although a significant positive association was observed among younger men ( < 59 years ) screened for prostate cancer ( RR , 1.49 ; 95 % CI , 1.08 - 2.06 ; Pinteraction = 0.006 ) . Conclusions : Gonorrhea and syphilis do not seem to be risk factors for prostate cancer in this cohort of men with a lower burden of sexually transmitted infections . Clinical prostatitis is also unlikely to be a risk factor , although possible roles for prostatitis in younger men and asymptomatic prostatic infection and inflammation can not be ruled out . ( Cancer Epidemiol Biomarkers Prev 2006;5(11):2160–6 Abstract Prospect i ve and retrospective epidemiological studies have been conducted to study the relation between benign prostatic hyperplasia ( B.P.H. ) and prostate cancer . In the prospect i ve study , 296 B.P.H. cases and 299 age-matched controls were traced until death or Dec. 31 , 1972 . The age-adjusted death-rate from prostate cancer was 3·7 times higher in the B.P.H. group than in the controls . For the retrospective study , hospital records of 290 prostate-cancer cases and 290 age-matched controls were compared . Matched-pair analysis of the antecedent hospital admissions revealed a relative risk of 5·1 for prostate cancer in patients seen earlier for benign prostatic enlargement . These findings suggest the need for a controlled clinical trial of prostatectomy as a preventive measure for prostatic cancer in symptom-free B.P.H. patients who have additional epidemiological characteristics associated with a high risk for prostate cancer OBJECTIVES To describe the prevalence and correlates of self-reported history of prostatitis in terms of lower urinary tract symptoms and associated dissatisfaction in community-dwelling older men . METHODS We performed a cross-sectional analysis from a prospect i ve cohort study of 5821 men aged 65 years and older recruited from six clinical centers . RESULTS Overall , 1439 men ( 25 % ) self-reported a history of prostatitis . Men with a history of prostatitis were more likely to self-report a history of prostate cancer ( 26 % versus 7 % ; P < 0.0001 ) and a history of benign prostatic hyperplasia ( 83 % versus 38 % ; P < 0.0001 ) within a lifetime compared with men without a history of prostatitis . Men with a history of prostatitis also had a greater mean American Urological Association symptom score ( mean + /- SD , 10.1 + /- 7.1 versus 7.7 + /- 5.9 ; P < 0.0001 ) than men without a history of prostatitis . Also , a greater percentage of men with a history of prostatitis reported being dissatisfied with their present urinary condition than did men without a history of prostatitis ( 21 % versus 11 % ; P < 0.0001 ) . We found positive associations for a history of prostatitis with a history of benign prostatic hyperplasia ( odds ratio 8.0 , 95 % confidence interval 6.8 to 9.5 ) , a history of prostate cancer ( odds ratio 5.4 , 95 % confidence interval 4.4 to 6.6 ) , and dissatisfaction with current urinary condition ( odds ratio 1.2 , 95 % confidence interval 1.01 to 1.5 ) . CONCLUSIONS A self-reported history of prostatitis is common in older men and was associated with self-reported prostate cancer and benign prostatic hyperplasia and increased severity of lower urinary tract symptoms and associated dissatisfaction . Because of the potential detection bias , recall bias , and the cross-sectional nature of the study , limiting causal inference , the associations among these urologic conditions require additional study This study aims to explore the association between fruit and vegetable intake , high fat , body mass index ( BMI ) score , physical activity , and the occurrence of prostate cancer among Jordanian men . A case-control study was conducted in three large referral hospitals . The sample included 165 prostate cancer patients in the case group and 177 healthy participants in the control group . The results showed that smoking ( odds ratio [ OR ] = 0.32 ; 95 % confidence interval [ CI ] = [ 0.18 , 0.57 ] ) , a history of prostate infection ( OR = 0.21 ; 95 % CI = [ 0.11 , 0.38 ] ) , high-fat intake ( OR = 0.44 ; 95 % CI = [ 0.23 , 0.85 ] ) , and increased mean of BMI ( OR = 1.08 ; 95 % CI = [ 1.02 , 1.13 ] ) increased the likelihood of developing prostate cancer . Healthy diet and giving up smoking are recommended , as they may contribute to a reduction in the incidence of prostate cancer . More r and omized clinical trials in this area are needed to strengthen the available evidence and reduce the effects of confounding variables Red wine contains polyphenol antioxidants that inhibit prostate cancer development in animal studies . We investigated the effect of red wine intake on the risk of prostate cancer using data prospect ively collected in the California Men 's Health Study ( CMHS ) . CMHS is a multiethnic cohort of 84,170 men aged 45–69 years who were members of the Kaiser Permanente Southern and Northern California Health Plans . Information on demographic and lifestyle factors was collected using mailed question naires between 2002 and 2003 . We used Cox models to estimate the effect of red wine on prostate cancer risk , adjusting for potential confounders . A total of 1,340 incident prostate cancer cases identified from Surveillance , Epidemiology and End Result ‐affiliated cancer registries were included in the analyses . We did not find a clear association between red wine intake and risk of prostate cancer . Hazard ratio ( HR ) estimates for consuming < 1 drink/week , ≥1 drink/week but < 1 drink/day and ≥1 drink/day were 0.89 , 95 % confidence interval ( 0.74–1.07 ) , 0.99 ( 0.83–1.17 ) and 0.88 ( 0.70–1.12 ) , respectively . Further , we observed no linear dose response . The lack of association for red wine intake was consistently observed when we restricted the analyses to those with and without a history of PSA screening . In addition , we also did not observe any association with prostate cancer for beer , white wine , liquor or combined alcoholic beverage intake ( HR for combined alcoholic beverage intake of ≥5 drinks/day = 1.16 ( 0.83–1.63 ) . Neither red wine nor total alcohol consumption were associated with prostate cancer risk in this population of moderate drinkers |
12,124 | 32,233,626 | The results of meta- analysis indicate that breathing exercises can improve pressure generated by the lower oesophageal sphincter ( LES ) , and a statistically significant difference was observed .
The possible mechanism behind this is the enhancement of the anti-regurgitation barrier [ especially crural diaphragm ( CD ) tension ] .
CONCLUSIONS To some extent , breathing exercises can relieve the symptoms of patients with GERD | BACKGROUND Breathing exercises can improve the symptoms of patients with gastroesophageal reflux disease ( GERD ) , but their specific effect and function are disputed .
To evaluate and conduct a meta- analysis on the effect of breathing exercises on patients with GERD . | Background & Aims In patients with gastroesophageal reflux disease ( GERD ) and excessive belching , most belches are supragastric , and can induce reflux episodes and worsen GERD . Supragastric belching ( SGB ) might be reduced with diaphragmatic breathing exercises . We investigated whether diaphragmatic breathing therapy is effective in reducing belching and proton pump inhibitor (PPI)‐refractory gastroesophageal reflux symptoms . Methods We performed a prospect i ve study of 36 consecutive patients with GERD refractory to PPI therapy and a belching visual analogue scale ( VAS ) score of 6 or more , seen at a gastroenterology clinic at a tertiary hospital in Singapore from April 2015 through October 2016 . Patients underwent high‐resolution manometry and 24‐hour pH‐impedance studies while they were off PPIs . Fifteen patients were placed on a st and ardized diaphragmatic breathing exercise protocol ( treatment group ) and completed question naires at baseline , after diaphragmatic breathing therapy , and 4 months after the therapy ended . Twenty‐one patients were placed on a waitlist ( control subjects ) , completed the same question naires with an additional question naire after their waitlist period , and eventually received diaphragmatic breathing therapy . The primary outcome was reduction in belching VAS by 50 % or more after treatment . Secondary outcomes included GERD symptoms ( evaluated using the reflux disease question naire ) and quality of life ( QoL ) scores , determined from the Reflux‐Qual Short Form and EuroQoL‐VAS . Results Nine of the 15 patients in the treatment group ( 60 % ) and none of the 21 control subjects achieved the primary outcome ( P < .001 ) . In the treatment group , the mean belching VAS score decreased from 7.1 ± 1.5 at baseline to 3.5 ± 2.0 after diaphragmatic breathing therapy ; in the control group , the mean VAS score was 7.6 ± 1.1 at baseline and 7.4 ± 1.3 after the waitlist period . Eighty percent of patients in the treatment group significantly reduced belching frequency compared with 19 % in control subjects ( P = .001 ) . Treatment significantly reduced symptoms of GERD ( the mean reflux disease question naire score decreased by 12.2 in the treatment group and 3.1 in the control group ; P = .01 ) . The treatment significantly increased QoL scores ( the mean Reflux‐Qual Short Form score increased by 15.4 in the treatment group and 5.2 in the control group ; P = .04 ) and mean EuroQoL‐VAS scores ( 15.7 increase in treatment group and 2.4 decrease in the control group ) . These changes were sustained at 4 months after treatment . In the end , 20 of the 36 patients who received diaphragmatic breathing therapy ( 55.6 % ) , all with excessive SGB , achieved the primary outcome . Conclusions In a prospect i ve study , we found a st and ardized protocol for diaphragmatic breathing to reduce belching and PPI‐refractory gastroesophageal reflux symptoms , and increase QoL in patients with PPI‐refractory GERD with belching — especially those with excessive SGB OBJECTIVES : The lower esophageal sphincter ( LES ) , surrounded by diaphragmatic muscle , prevents gastroesophageal reflux . When these structures become incompetent , gastric contents may cause gastroesophageal reflux disease ( GERD ) . For treatment , lifestyle interventions are always recommended . We hypothesized that by actively training the crura of the diaphragm as part of the LES using breathing training exercises , GERD can be positively influenced . METHODS : A prospect i ve r and omized controlled study was performed . Patients with non-erosive GERD or healed esophagitis without large hernia and /or previous surgery were included . Patients were r and omized and allocated either to active breathing training program or to a control group . Quality of life ( QoL ) , pH-metry , and on-dem and proton pump inhibitor ( PPI ) usage were assessed at baseline and after 4 weeks of training . For long-term follow-up , all patients were invited to continue active breathing training and were further assessed regarding QoL and PPI usage after 9 months . Paired and unpaired t-test was used for statistical analysis . RESULTS : Nineteen patients with non-erosive GERD or healed esophagitis were r and omized into two groups ( 10 training group and 9 control group ) . There was no difference in baseline patient characteristics between the groups and all patients finished the study . There was a significant decrease in time with a pH<4.0 in the training group ( 9.1±1.3 vs. 4.7±0.9 % ; P<0.05 ) , but there was no change in the control group . QoL scores improved significantly in the training group ( 13.4±1.98 before and 10.8±1.86 after training ; P<0.01 ) , but no changes in QoL were seen in the control group . At long-term follow-up at 9 months , patients who continued breathing exercise ( 11/19 ) showed a significant decrease in QoL scores and PPI usage ( 15.1±2.2 vs. 9.7±1.6 ; 98±34 vs. 25±12 mg/week , respectively ; P<0.05 ) , whereas patients who did not train had no long-term effect . CONCLUSIONS : We show that actively training the diaphragm by breathing exercise can improve GERD as assessed by pH-metry , QoL scores and PPI usage . This non-pharmacological lifestyle intervention could help to reduce the disease burden of GERD The crural diaphragm ( CD ) is an essential component of the esophagogastric junction ( EGJ ) , and inspiratory exercises may modify its function . This study 's goal is to verify if inspiratory muscle training ( IMT ) improves EGJ motility and gastroesophageal reflux ( GER ) . Twelve GER disease [ GERD ; 7 males , 20 - 47 yr , 9 esophagitis , and 3 nonerosive reflex disease ( NERD ) ] and 7 healthy volunteers ( 3 males , 20 - 41 yr ) performed esophageal pH monitoring , manometry , and heart rate variability ( HRV ) studies . A 6-cm sleeve catheter measured average EGJ pressure during resting , peak inspiratory EGJ pressures during sinus arrhythmia maneuver ( SAM ) and inhalations under 17- , 35- , and 70-cmH2O loads ( TH maneuvers ) , and along 1 h after a meal . GERD patients entered a 5-days-a-week IMT program . One author scored heartburn and regurgitation before and after IMT . IMT increased average EGJ pressure ( 19.7 ± 2.4 vs. 29.5 ± 2.1 mmHg ; P < 0.001 ) and inspiratory EGJ pressure during SAM ( 89.6 ± 7.6 vs. 125.6 ± 13.3 mmHg ; P = 0.001 ) and during TH maneuvers . The EGJ-pressure gain across 35- and 70-cmH2O loads was lower for GERD volunteers . The number and cumulative duration of the transient lower esophageal sphincter relaxations decreased after IMT . Proximal progression of GER decreased after IMT but not the distal acid exposure . Low-frequency power increased after IMT and the higher its increment the lower the increment of supine acid exposure . IMT decreased heartburn and regurgitation scores . In conclusion , IMT improved EGJ pressure , reduced GER proximal progression , and reduced GERD symptoms . Some GERD patients have a CD failure , and IMT may prove beneficial as a GERD add-on treatment The treatment of gastroesophageal reflux disease may be clinical or surgical . The clinical consists basically of the use of drugs ; however , there are new techniques to complement this treatment , osteopathic intervention in the diaphragmatic muscle is one these . The objective of the study is to compare pressure values in the examination of esophageal manometry of the lower esophageal sphincter ( LES ) before and immediately after osteopathic intervention in the diaphragm muscle . Thirty-eight patients with gastroesophageal reflux disease - 16 su bmi tted to sham technique and 22 su bmi tted osteopathic technique - were r and omly selected . The average respiratory pressure ( ARP ) and the maximum expiratory pressure ( MEP ) of the LES were measured by manometry before and after osteopathic technique at the point of highest pressure . Statistical analysis was performed using the Student 's t-test and Mann-Whitney , and magnitude of the technique proposed was measured using the Cohen 's index . Statistically significant difference in the osteopathic technique was found in three out of four in relation to the group of patients who performed the sham technique for the following measures of LES pressure : ARP with P= 0.027 . The MEP had no statistical difference ( P= 0.146 ) . The values of Cohen d for the same measures were : ARP with d= 0.80 and MEP d= 0.52 . Osteopathic manipulative technique produces a positive increment in the LES region soon after its performance |
12,125 | 23,057,701 | The results from network meta- analysis showed that most active treatment options had significantly better treatment outcome than placebo | AIM Dentin hypersensitivity , caused by the exposure and patency of dentinal tubules , can affect patients ' quality of life .
The aim of this study was to undertake a systematic review and a network meta- analysis , comparing the effectiveness in resolving dentin hypersensitivity among different in-office desensitizing treatments . | The aim of this study was to evaluate the efficacy of two desensitizing agents in the reduction of dentin hypersensitivity in a r and omized , double-blind , split-mouth clinical trial . Seventy-seven teeth from 13 patients that presented some degree of sensitivity to probing and /or air stimulation were treated with one of the following desensitizing agents : Oxa-Gel ( G1 ) , Sensi Kill ( G2 ) and placebo gel ( G3 - control ) . According to paired t-test , all treatments , even the placebo gel , were capable of reducing sensitivity scores for both stimuli . Analysis of data by ANOVA and Tukey 's test ( ? = 0.05 ) showed that the sensitivity scores were significantly lower only for Sensi Kill in comparison to the other products ( Oxa-Gel and placebo ) , when air stimulus was applied . It may be concluded that treatment with Sensi Kill presented a slightly better performance in reducing dentin hypersensitivity when compared to the other desensitizing agent INTRODUCTION Various methods and material s are used in the treatment of dentin hypersensitivity . The aim of this r and omized prospect i ve controlled clinical trial was to evaluate and compare the desensitizing effects of the neodymium-doped yttrium aluminium garnet ( Nd : YAG ) laser and fluoride varnish by considering the degree of pre- and posttreatment pain , discomfort , and functional complications . METHODS Twenty patients with clinical ly diagnosed cervical dentin hypersensitive teeth were included and r and omly allocated to either the application of fluoride varnish ( group fluoride ) or Nd : YAG laser ( 100 mJ , 20 Hz ; group Nd : YAG ) . The assessment of pain and discomfort was performed by a visual analog scale after an air blast at baseline , immediately after treatment , and at patient visits on weeks 1 , 2 , 3 , and 4 . RESULTS Laser treatment result ed in significant improvements of discomfort immediately after treatment and after 1 week . At the 2- , 3- , and 4-week examination , the discomfort in group fluoride decreased up to nearly 75 % to 85 % of baseline scores , whereas the effect of the laser stayed nearly unchanged . The visual analog scale scores for pain at 4 weeks examination were significantly lower in the fluoride group compared with those in the laser group ( p < 0.05 ) . CONCLUSIONS Nd : YAG laser is a suitable tool for the immediately successful reduction of dentinal hypersensitivity and has better patient satisfaction and shorter treatment time OBJECTIVE Dentin hypersensitivity , or what patients may describe as " sensitive teeth , " is defined as a short , sharp pain arising from exposed dentin in response to thermal , evaporative , tactile , electrical , osmotic or chemical stimuli . It is widely accepted that dentin hypersensitivity is an uncomfortable condition that also affects function and quality of life . This study determines the differences in efficiency of three desensitizing products when compared with a placebo . METHODS A r and omized controlled clinical trial was conducted to compare three different professional dentin desensitizer agents in 52 patients . The age and sex of the patients was recorded . Gluma Desensitizer ( Heraeus Kulzer ) , UltraEZ ( Ultradent Products , Inc ) and Duraphat ( Colgate Oral Pharmaceuticals , Inc , New York , NY , USA ) were used as desensitizer agents and distilled water was used as the placebo . The baseline measurement of the dentin hypersensitivity was made by using a visual analog scale ( VAS ) . Twenty-four hours and seven days after application of the desensitizer agents and placebo , a new VAS analysis was conducted for patients ' sensitivity level . The desensitizer agents were compared in terms of mean values , and ANOVA was used for testing differences among the groups ( p<0.05 ) . RESULTS The results showed that the mean pain scores of the placebo group were significantly higher than that of the study groups ( p<0.05 ) . The VAS analysis revealed a significant decrease in dentin hypersensitivity over time with the use of agents ( p<0.05 ) . No statistically significant difference was found among the three desensitizing agents ( p>0.05 ) . CONCLUSIONS These three desensitizing agents , which contain different active ingredients , were effective in relieving dentin hypersensitivity . However , no superiority was found in dentin sensitivity relief among the agents OBJECTIVE The advent of dental lasers has raised another possible treatment option for dentine hypersensitivity ( DH ) and has become a research interest in the last decades . The aim of this r and omized , controlled , double-blind , split mouth , clinical study was to evaluate and compare the desensitizing effects of erbium , chromium-doped : yttrium , sc and ium , gallium and garnet ( Er , Cr : YSGG ) to galium-aluminium-arsenide ( GaAlAs ) laser on DH . METHODS Fifty-one patients participated in this study for a total of 174 teeth . DH was assessed for all groups with a visual analog scale . For each patient , the teeth were r and omized to three groups . In the diode laser group , sensitive teeth were irradiated with the GaAlAs laser at 8.5J/cm(2 ) energy density . In the Er , Cr : YSGG laser group , sensitive teeth were irradiated with Er , Cr : YSGG laser in the hard tissue mode using a none-contact probe at an energy level of 0.25W and repetition rate of 20Hz , 0 % water and 10 % air . In the control group no treatment was performed . Treatment time was 60s for GaAlAs laser and 30s for Er , Cr : YSGG laser . RESULTS When compared with the control group and baseline data , in both laser groups , laser irradiation provided a desensitizing effect immediately after treatment and this effect was maintained throughout the study ( p<0.05 ) . No significant differences between Er , Cr : YSGG and GaAlAs laser groups were found at any follow-up examination ( p>0.05 ) . CONCLUSION Based on these findings , it may be concluded that both Er , Cr : YSGG and GaAlAs lasers were effective in the treatment of DH following a single application UNLABELLED The dentin hypersensitivity is a painful condition rather prevalent in the general population . There are several ways of treatment for such condition , including the low intensity lasers . The proposal of this study was to verify the effectiveness of the Gallium-Aluminum-Arsenide diode laser in the treatment of this painful condition , using a placebo as control . MATERIAL S AND METHODS Thirty-two patients were selected , 22 females and 10 males , with ages ranging from 20 to 52 years old . The 32 patients were r and omly distributed into two groups , treated and control ; the sample consisted of 68 teeth , 35 in the treated group and 33 in the control group . The treated group was exposed to six laser applications with intervals from 48 to 72 hours , and the control group received , as placebo , applications of a curing light . RESULTS A significant reduction was observed in the pain condition between the initial phase and after six laser applications ; however , such reduction could also be observed for the control group exposed to the placebo . CONCLUSION Therapy with the low intensity Gallium-Aluminum-Arsenide laser - AsGaAl induces a statistically significant reduction in the painful condition after each application and between the beginning and end of treatment , although there was no statistically significant difference between the treated group ( laser ) and the control group ( placebo ) at the end of treatment and after the mediate evaluation results ( after 6 weeks ) , this way impairing the real measurement of laser effectiveness and placebo effect OBJECTIVES The purpose of this study was to evaluate and compare clinical ly the efficacy of desensitizer toothpaste alone and in combination with the diode laser in the management of dentin hypersensitivity ( DH ) , as well as both the immediate and late therapeutic effects on teeth with gingival recessions . MATERIAL S AND METHODS In total , 52 teeth diagnosed with DH in 13 ( seven women , six men , aged 16 - 48 years ) healthy adult patients were included in this study , and teeth were r and omly divided equally into two groups : the test group , which received treatment with desensitizer toothpaste and GaAlAs ( diode ) laser , and the control group , treated with desensitizer toothpaste . DH was assessed by means of an air stimulus , and a visual analogue scale ( VAS ) was used to measure DH . The selected teeth in the test group received laser therapy for three sessions . Teeth subjected to diode-laser treatment were irradiated at 100 mW for 25 sec at 808 nm , with continuous-emission , noncontact mode , perpendicular to the surface , with scanning movements on the region of exposed root surfaces . RESULTS Significant reduction of DH occurred at all times measured during the three treatment sessions in the test group . When compared with the means of the responses in the three treatment sessions of the two groups , the test group showed a higher degree of desensitization in teeth with gingival recession than did the control group ( p < 0.001 ) . The immediate and late therapeutic effects of the diode laser were more evident compared with those of desensitizer toothpaste . CONCLUSIONS Within the limitations of the present study , a significant effect of combined desensitizer toothpaste and diode laser therapy occurs in the treatment of desensitization of teeth with gingival recession . Desensitizer toothpaste appears to have the therapeutic potential to alleviate DH . Conversely , diode laser can be used to reduce DH This double-blind split-mouth trial with 16 adult patients investigated the ability of a dentine bonding agent ( DBA ) to reduce cervical dentine sensitivity . Following stimulation of pairs of teeth by conventional tactile and air blast stimuli , together with controlled evaporative and cold fluid stimuli , sensitivity was recorded using tactile threshold , visual-analogue scale ( VAS ) and short-form McGill pain question naire ( SFMPQ ) , prior to and 1 week following treatment with DBA . Prior to assessment , subjects recorded their perceived overall sensitivity using VAS and SFMPQ . Application of each stimulus was separated by 10 min . Sensitivity was recorded by a clinician blinded to the treatment status of each tooth . The control tooth was treated by applying DBA to coronal enamel . Dietary information was collected after the post-treatment assessment . There was a significant ( p<0.05 ) improvement in tactile threshold and air flow and air blast VAS scores , together with reductions in sensitivity to evaporative stimuli when assessed by SFMPQ . Treatment response was not influenced by the subjects ' age , gender , diet , use of fluoride-containing or silica-based toothpastes or fluoride mouthwashes , or a history of previous sensitivity treatment . It is concluded that topical application of DBA is an effective way to reduce cervical dentine sensitivity This study compares two commercially-available products for treating dentine sensitivity , Duraphat , a fluoride varnish , and SuperSeal , an oxalate preparation . 48 patients with dentine sensitivity were recruited . Sensitivity was assessed by visual analogue scales ( VAS ) to record pain following stimulation of exposed dentine surfaces by tactile stimulus ( sharp probe at 60 g force ) , thermal stimulus ( ethyl chloride ) and evaporative stimulus ( air drying ) . Patients were r and omised to treatment with either Duraphat or SuperSeal . After 4 weeks , sensitivity assessment s were repeated . Both treatments result ed in statistically significant reductions in VAS scores for all stimuli ( P<0.05 ) . However , analysis of covariance failed to identify statistically significant differences in the magnitude of reductions in sensitivity achieved by each of the products ( P>0.05 ) . The treatments had similar efficacy and both can be considered effective therapies for treating dentine sensitivity The aim of this clinical trial was to investigate the effects of topical applications of Gluma 3 Primer or Gluma 2000 conditioning solutions on hypersensitive erosion/abrasion lesions . Thirty-four patients were included in the trial with at least two teeth each presenting severe sensitivity . From a total of 116 teeth , 40 were treated with Gluma 3 Primer , 42 with Gluma 2000 Conditioner and 34 served as the control . Sensitivity was recorded as response to tactile and cold air stimuli prior to treatment as baseline , immediately after the topical application of the agents , after 1 week , 1 month and 6 months . Both Gluma groups showed a highly significant reduction in sensitivity between baseline and postoperative pain scores ( P < 0.05 ) and between the postoperative and the 1-week responses ( P < 0.05 ) . The sensitivity scores were not different between 1 week and 6 months . In the control group , no pain reduction was registered between baseline and up to 1-month recall . After 6 months , however , the sensitivity was spontaneously slightly reduced . At the end of the 6-month observation time , 29 Gluma and 31 Gluma 2000 treated teeth no longer showed dentin sensitivity OBJECTIVE The aim of the present study was to evaluate and compare the efficacy of CO(2 ) and Er : YAG lasers alone and in combination with topical sodium fluoride ( NaF ) in the management of dentine hypersensitivity . MATERIAL S AND METHODS A group of 50 patients presenting with a total of 420 hypersensitive teeth were r and omly allocated into five groups . Group 1 was treated with 2 % NaF , groups 2 and 3 were lased by a CO(2 ) ( 1 W , continuous wave mode , for 10 sec ) or Er : YAG ( 30 Hz , 60 mJ for 10 sec , without water/air spray ) laser , and groups 4 and 5 received NaF plus the CO(2 ) and the Er : YAG laser , respectively . The scanning speed of the laser was 0.8 mm/sec . The degree of thermal sensitivity was determined with an evaporative stimulus consisting of a 1-sec air blast at a distance of 2 mm from each site tested . Quantification of the degree of discomfort was determined according to a four-point pain scale before treatment and 1 wk , 1 mo , and 6 mo after treatment . RESULTS All treatment forms result ed in significant improvement of discomfort . At 1 wk , 1 mo , and 6 mo , cold air blast scores were significantly reduced compared to baseline scores , except for the NaF group . In the NaF group , there was a statistically significant increase in mean degree of discomfort at 6 mo compared with 1 wk ( p + /- 0.01 ) and 1 mo ( p + /- 0.001 ) . Comparison of the other treatment regimens revealed that cold air blast scores were significantly lower for the other four treatments than for NaF gel alone ( p + /- 0.001 ) . No superiority was found for desensitization among the CO(2 ) , Er : YAG , CO(2 ) + NaF , and Er : YAG + NaF groups . CONCLUSIONS We concluded that both the CO(2 ) and Er : YAG lasers have promising potential for the treatment of dentine hypersensitivity . Lasers in combination with NaF gel appear to show better efficacy compared to either treatment modality alone OBJECTIVE To compare the clinical efficacy of the GaAlAs laser and dentin bonding agent in treating dentin hypersensitivity . METHODS One hundred and forty teeth from 70 patients diagnosed with dentin hypersensitivity , were divided into two groups : In group I , teeth were irradiated with 30 mW GaAlAs laser for 1 min and in group II , teeth were applied with dentin bonding agent . Sensitivity was assessed by tactile and thermal tests , measured with the criteria proposed by Uchida at baseline and after treatment ; immediately , at 15 and at 30 days . RESULTS The reduction of dentin hypersensitivity was observed in both treatments using the GaAlAs laser and dentin bonding agent . However , a greater reduction was observed over time up to day 15 and no significant change was observed between days 15 and 30 . Statistically significant differences in the level of dentin hypersensitivity between bonding agent and the GaAlAs laser were found at each observation period ( p < 0.05 ) . CONCLUSION The GaAlAs laser had less desensitizing efficacy compared with dentin bonding agent . However , the desensitizing effect of the GaAlAs laser still could be considered an effective therapy for treating dentin hypersensitivity Clinical trials on dentine hypersensitivity have been numerous and protocol s varied . To date there is little consensus as to the conduct of studies on this poorly-understood yet common and painful dental condition . A committee of interested persons from academia and industry was convened to discuss the subject of clinical trials on dentine hypersensitivity and a consensus report is presented . A double-blind r and omized parallel groups design is recommended , although cross-over design s may be used for the preliminary screening of agents . Subjects may have multiple sites scored . Sample size will be determined by estimating the variability in the study population , the effect to be detected and the power of the statistical test to be used . Subject selection is based on a clinical diagnosis of dentine hypersensitivity , excluding those with conflicting characteristics such as currently-active medical or dental therapy . The vestibular surfaces of incisors , cuspids and bicuspids are preferred as sites to be tested . A range of sensitivity levels should be included . Tactile , cold and evaporative air stimuli should be applied . Negative and benchmark controls should be incorporated . Most trials should last 8 weeks . Sensitivity may be assessed either in terms of the stimulus intensity required to evoke pain or the subjective evaluation of pain produced by a stimulus using a visual analog or other appropriate scale . The subject 's overall assessment may be determined by question naire . Outcomes should be expressed in terms of clinical ly significant changes in symptoms . Follow-up evaluation is required to determine the persistence of changes . At least 2 independent trials should be conducted before a product receives approval PURPOSE To evaluate the effectiveness of a dentin bonding agent containing HEMA compared to a resin emulsion in the reduction of cervical dentin hypersensitivity ( CDH ) . MATERIAL S AND METHODS The study was a r and omized-within-subject , double blind design . Twenty patients who were suffering from CDH from at least two teeth ( canines and /or premolars ) were enrolled . The subjective perceptions of pain in response to tactile , air blasts and cold ethyl chloride stimuli were evaluated using a visual analog scale ( VAS ) at baseline and 10 minutes , 1 week and 4 weeks after the treatments . Scotchbond 1 ( a dentin bonding agent similar to Single Bond in the USA ) and MS Coat ( a resin emulsion ) , both applied according to the manufacturers ' directions , were selected for the study . RESULTS Multiple regression ANOVA for repeated measures showed that both treatments significantly reduced the CDS with respect the baseline values after just 10 minutes . There were no significant differences between the ability of the two treatments to reduce CDH for each of the three evaluation stimuli or for subjective evaluation OBJECTIVE The aim of this clinical study was to evaluate and compare the desensitizing effects of a gallium?aluminum?arsenide ( GaAlAs ) laser and sodium fluoride ( NaF ) varnish on dentine hypersensitivity ( DH ) in periodontal maintenance patients . BACKGROUND DATA The use of lasers opens a new dimension in the treatment of DH . METHODS Forty-eight patients with 244 teeth affected by DH were included in the trial . To be included in the study , the subjects had to have 4 or more hypersensitive teeth at different quadrants . Selected teeth were r and omly assigned to a GaAlAs laser group , placebo laser group , NaF varnish group , or a placebo NaF varnish group . Laser therapy was performed at 8.5?J/cm(2 ) energy density . In the placebo laser group , the same laser without laser emission was used . In the NaF varnish group , the varnish was painted at the cervical region of the teeth . In the placebo NaF varnish group , the same treatment procedures were performed with a saline solution . DH was assessed with a visual analog scale ( VAS ) ; immediately , at 1 week , and at 1 , 3 , and 6 months after treatments . Intra-group time-dependent data were analyzed by Friedman 's test , and Wilcoxon 's rank sum test was used to evaluate the differences within groups . RESULTS GaAlAs laser and NaF varnish treatments result ed in a significant reduction in the VAS scores immediately after treatments that were maintained throughout the study when compared to the baseline and placebo treatments . In the NaF group , there was a significant increase in the VAS scores at 3 and 6 months compared to at 1 week and 1 month . The placebo treatments showed no significant changes in VAS scores throughout the study period . CONCLUSIONS Within the limits of the study , GaAlAs laser irradiation was effective in the treatment of DH , and it is a more comfortable and faster procedure than traditional DH treatment OBJECTIVES This study evaluated the immediate and 3 month clinical effects of a low-level gallium-aluminum-arsenide ( GaAlAs ) laser and a 3 % potassium oxalate gel for the treatment of dentinal hypersensitivity . MATERIAL S AND METHODS A total of 164 teeth from 30 patients with clinical diagnoses of dentinal hypersensitivity were selected for this r and omized , placebo-controlled , double-blind clinical study . The teeth were r and omized to three groups : GaAlAs laser , oxalate gel , and placebo gel . The treatment sessions were performed at 7 d intervals for four consecutive weeks . The degree of sensitivity in response to an air blast and tactile stimuli was assessed according to a visual analogue scale at baseline , immediately after the fourth application , and then 3 months after the fourth application . The reductions in dentinal hypersensitivity from baseline at the two follow-up assessment s were evaluated as the main outcome . RESULTS In both the active and control groups , there were statistically significant reductions in dentinal hypersensitivity immediately after and 3 months after the treatments , when compared with the hypersensitivity at baseline . No significant differences among the three groups could be detected in their efficacy at either the immediate or 3 month evaluations irrespective of the stimulus . CONCLUSIONS The treatments under study were effective for reducing dentinal hypersensitivity , and longer observational periods could enhance the ability of studies to detect differences between active and placebo groups Abstract The purpose of this double-blind study was to evaluate the effectiveness of a commercially available fluoride lacquer ( Bifluorid 12 ) containing CaF2 ( 6 % ) and NaF ( 6 % ) in reducing dentine hypersensitivity . A fluoride lacquer containing only NaF ( 6 % ) served as a control . Twenty-five adult patients complaining about at least two hypersensitive teeth participated in this study . In each patient and at each appointment , one tooth was treated with Bi-fluorid 12 , while the other was treated with the control substance . Sensitivity levels were determined before and after the application of each lacquer at baseline as well as at 1 , 2 and 3 weeks after the start of study . The final evaluation of hypersensitivity was performed at 4 weeks , and follow-ups were undertaken at 6 and 12 months . A reproducible air blast stimulus and a visual analogue scale were used for evaluation . Results demonstrated a distinct reduction of hypersensitivity after 1 , 2 and 3 weeks in the Bi-fluorid 12 group . Initially , no obvious effects could be observed in the control group . However , a clear alleviation could be observed after 2 and 3 weeks with the control . After 4 weeks , the overall sensitivity scores were comparably low , without any significant differences between the two fluoride lacquers . In both groups , the effects of treatment were seen over the 12-month observation period . Bifluorid 12 was considered at least comparable to the control . It is concluded from this study that Bifluorid 12 is effective in the initial reduction of dentine hypersensitivity . The combination of CaF2/NaF can be recommended for clinical use The aim of this study was to evaluate low-level laser therapy in cervical dentin hypersensitivity . A r and omized controlled clinical trial was conducted with a total of 64 teeth . Dentin desensitizer and diode laser were applied on the cervical dentin surfaces . Distilled water and placebo laser was used as the placebo groups . The irradiance used was 4 J/cm2 per treatment site . The baseline measurement of hypersensitivity was made by using visual analog scale ( VAS ) . Twenty-four hours and 7 days after the application of desensitizer , diode laser and placebo groups , a new VAS analysis was conducted for the patients ’ sensitivity level . The mean pain scores of placebo groups were significantly higher than the desensitizer ’s and diode laser ’s mean scores ( ANOVA , p < 0.05 ) . The VAS analysis revealed a significant decrease in dentin hypersensitivity in 7 days with the use of the desensitizer and low-level laser therapy and no statistically significant difference was observed between these two treatments ( p > 0.05 ) . Although low-level laser and glutaraldehyde containing desensitizer present distinct modes of action , experimental agents caused a significant reduction of dentin hypersensitivity without showing secondary effects , not irritating the pulp or causing pain , not discoloring or staining the teeth , and not irritating the soft tissues at least for a period of 1 week with no drawbacks regarding h and ling and /or ease of application . Low-level laser therapy and desensitizer application had displayed similar effectiveness in reducing moderate dentin hypersensitivity BACKGROUND , AIMS Promising results using Nd : YAG laser against dentin hypersensitivity have been reported . The aim of this double-blind , controlled , split-mouth design ed clinical trial was to assess the effect of a single Nd : YAG laser application on alleviating hypersensitivity . METHODS / RESULTS Seventeen subjects participated in the study . Each of them had two teeth treated ; one with the laser activated and one with nonactivated ( placebo ) , for 2 min The assessment of pain was performed by a VAS , after an air blast at baseline immediately after treatment , at 1 week , 4 weeks and 16 weeks . Mean values of VAS for test and control teeth were compared by paired t-test ( alpha = 0.05 ) . The results showed mean baseline VAS values of 6.59 ( + /- 1.65 ) and 6.14(+/- 1.95 ) for test and control teeth , respectively . Immediately after treatment , these values decreased to 4.09(+/- 2.28 ) and 3.89(+/- 2.11 ) , respectively . After 1 week , 4 weeks and 16 weeks the mean values for test and control teeth were 3.85 + /- 2.36 , 4.03 + /- 1.95 , 3.60 + /- 2.66 , and 4.44 + /- 2.56 , 3.41 + /- 2.30 , 3.42 + /- 2.30 , respectively . There were no statistically significant differences between test and control at any time . However , both groups improved significantly ( P < 0.05 ) from baseline to immediately after application , and at 1 week , 4 weeks and 16 weeks , respectively . The changes that occurred between immediately after application and 1 week , 4 weeks and 16 weeks , respectively , were not statistically significant . CONCLUSION It is concluded that the effect of treatment of hypersensitive teeth with Nd : YAG laser is not different from placebo . The observed effects seem to last for at least 16 weeks Many treatments for dentine hypersensitivity are formulated to directly or indirectly occlude the open dentinal tubules associated with the condition . Combining solutions of calcium chloride and potassium phosphate can result in the precipitation of amorphous calcium phosphate . Such a system applied to exposed dentine could occlude dentinal tubules and reduce sensitivity . The aims of this study using a placebo control were to assess the therapeutic value of amorphous calcium phosphate in dentine hypersensitivity and provide further information on the apparently natural improvement in the condition frequently observed in clinical trials . 38 subjects with dentine hypersensitivity affecting 1 tooth in each left and right sides of the jaws were recruited into this split mouth , r and omised , double-blind study . At baseline , sensitivity was scored by the subjects on a 0 - 10 visual apologue scale after tactile , cool and cold water and evaporative stimulation of the test teeth . Active and control , water , solutions were then applied by a 2nd clinician . After 24 h , subjects returned for rescoring . On days 7 and 14 , subjects were again rescored and the treatments reapplied . Further follow-up appointments for rescoring were on days 21 , 28 , 56 and 84 . Plaque scores also were recorded from test teeth at each visit . Overall sensitivity decreased considerably and to a similar degree in test and control teeth with no consistent significant treatment difference . Plaque scores also decreased through the study period . It is concluded that either the amorphous calcium phosphate was without therapeutic effect or the activity was masked by the placebo response in the control teeth PURPOSE To compare the effectiveness of an agent that promotes deposition of amorphous calcium phosphate ( Quell Desensitizer ) to a commonly used product , sodium fluoride solution ( Nupro Neutral ) , in the reduction of root sensitivity after periodontal therapy , in a prospect i ve , convenient sample , double-blind clinical trial . METHODS Thirty patients were enrolled and treated , result ing in 40 teeth treated with the test product and 40 teeth treated with the control product . The clinical parameters tested at baseline and in the follow-up visits ( 1 , 2 , and 4 weeks after treatment ) were the following : plaque index , gingival index , gingival recession , and response to mechanical and cold stimulation with airblast and ice . Patients were also asked to report the grade of pain response on a Visual Analogue Scale ( VAS ) on the same schedule as the clinical parameters . RESULTS Plaque index and gingival index were not significantly different between test and control groups throughout the study . Most recession was observed on midbuccal surfaces . Buccal surfaces evoked higher pain response compared to lingual surfaces . It was concluded that both control and test treatments reduced root sensitivity response reported with mechanical or cold stimulation . No statistically significant differences were observed when the data of both groups were compared by a Student 's t-test at the 0.05 level of significance Previous in vitro permeability and scanning electron microscopic ( SEM ) studies have demonstrated the effectiveness of the oxalate ion in dentine permeability reduction and effective tubule occlusion . The aim of this r and omized double-blind , split mouth 4-week clinical study , therefore was to determine whether a 1-min application of ferric oxalate ( Sensodyne Sealant ) on exposed root dentine was effective in reducing dentine hypersensitivity ( DH ) . Thirteen subjects [ 8F:5 M , mean age 46.2 ( s.d . 4.15 ) years ] completed the study . The subjective response was evaluated by tactile , thermal and evaporative methods of assessment . Data were collected at baseline and post-application at + 5 min and 4 weeks . Analysis was based on paired t-test ( P=0.05 ) and Wilcoxon-Mann-Whitney tests . No statistically significant differences were noted between ferric oxalate and placebo preparations at + 5 min and 4 weeks for any of the test stimuli . There was , however , a clear trend towards immediate reduction ( + 5 min ) in DH reverting back to baseline values at 4 weeks with the exception of the Biomat Thermal Probe mean values , which maintained the reductions in DH compared with placebo . The results of the present study demonstrated that a 1-min application of ferric oxalate is both rapid and effective in reducing DH although its long-term effectiveness still needs to be determined A comparative double blind study testing low level laser therapy ( Gallium/Aluminium/Arsenide laser [ GaAlAs ] ) against placebo was carried out in the management of dentinal tooth hypersensitivity . Subjects demonstrating dentinal hypersensitivity and complying with strict selection criteria were r and omly assigned to an active and placebo group . Low level laser therapy was applied for one minute to both the apex and cervical area of the tooth ; and reapplied at one week , two-week and eight-week intervals . Dentinal hypersensitivity was rated at each visit . There were 28 subjects in the placebo group and 22 and 21 subjects , respectively , in the tactile sensitivity and thermal sensitivity groups . Comparisons between the groups were conducted using independent groups t-test . In both the tactile and thermal sensitivity groups differences between the active and placebo groups were significant from the first week and increased further in the second and eighth weeks . The mean value of thermal sensitivity decreased 67 per cent ( p < 0.001 ) compared with placebo ( 17 per cent ) and tactile sensitivity decreased 65 per cent ( p = .002 ) compared with placebo ( 21 per cent ) at eight weeks . Results demonstrate that the GaAlAs laser is an effective method for the treatment of both thermal and tactile dentinal hypersensitivity . There were no reported adverse reactions or instances of oral irritation OBJECTIVES The null-hypothesis tested was ; there is no difference in effectiveness between a new low-viscosity glass ionomer and a resin-based glutaraldehyde containing primer in treating hypersensitive teeth after 2 years . METHODS Using a split-mouth design , hypersensitive teeth in 14 adult patients were r and omly assigned to 2 treatment groups . Hypersensitive tooth surfaces were covered with a low-viscosity glass ionomer ( Fuji VII ) and a resin-based glutaraldehyde containing primer ( Gluma Desensitizer ) . The discomfort interval scale ( DIS ) ranging from 0 to 4 was used to test the level of hypersensitivity before and after treatment , and at 3 months using compressed air blown for 2 s , and at 1 and 25.2 months using a telephone interview . Differences between and within the treatment groups were tested using the sign rank test . RESULTS Evaluations in the gluma group were discontinued after 3 months . The mean DIS score for hypersensitive teeth in the glass ionomer group was statistically significantly lower than that in the gluma group , immediately after application ( p=0.0005 ) , after 1 month ( p=0.02 ) and after 3 months ( p=0.003 ) . After 3 months , 11/14 of the hypersensitive teeth in the glass ionomer group and 2/14 in the gluma group were free of sensitivity . The mean DIS score for hypersensitive teeth in the glass ionomer group remained low after 19.2 months ( 0.25 : S.E.=0.13 ) and 25.2 months ( 0.22 : S.E.=0.15 ) . CONCLUSIONS The null-hypothesis was rejected . The low-viscosity glass ionomer ( Fuji VII ) is more effective in treating hypersensitive teeth than Gluma Desensitizer after 3 months . The positive treatment effect of the glass ionomer continued until 25.2 months BACKGROUND AND AIM Several dentifrices have shown to be effective in reducing dentine hypersensitivity ( DH ) , but more effective products are needed . The aim of the study was to evaluate the desensitizing efficacy of a new dentifrice based on zinc-carbonate hydroxyapatite ( CHA ) nanocrystals . METHODS AND MATERIAL S Using a double-blind , r and omized design , the new dentifrice was compared with potassium nitrate/fluoride dentifrice ( active control ) . The participant 's DH was evaluated at baseline and after 4 and 8 weeks using airblast ( primary outcome ) , tactile , cold water and subjective tests ( secondary outcomes ) . RESULTS The final sample consisted of 70 subjects with baseline DH ; 36 received the new dentifrice and 34 the control one . Both dentifrices were largely effective ; the percentage of score reduction from baseline to 8 weeks was greater than 28 % for all tests ( and greater than 55 % for the cold water test ) in both groups . As compared with controls , experimental subjects had a significantly greater improvement in the airblast test score ( mean percentage of reduction of 46.0%versus 29.4 % in controls ) and the subjective test score ( 47.5%versus 28.1 % , respectively ) , with both differences already being significant after 4 weeks . In contrast , there was no significant difference between groups for either the tactile or cold water tests at any time point and with any outcome . CONCLUSIONS This study documented that the new dentifrice containing zinc-CHA nanocrystals significantly reduced dentinal hypersensitivity after 4 and 8 weeks , supporting its utility in clinical practice PURPOSE To compare the clinical effect over 3 months of two commercially available desensitizing agents on the level of discomfort of patients with complaints of dentin sensitivity . MATERIAL S AND METHODS An oxalate-containing pre-polymerized resin suspension ( Pain-Free ) , a 0.7 % fluoride solution ( DentinBloc ) , and a distilled water placebo were compared in a clinical setting . Ten volunteer patients exhibiting three or more teeth that were sensitive to touch and to a stream of forced air were enrolled in the study ( 52 teeth total ) . Each patient 's level of sensitivity to tactile stimuli and to a forced air stream was recorded using a visual analog scale ( VAS ) . The tactile stimulus was a metal probe rubbed across the exposed dentin with a constant pressure of 40 grams . A 1-second blast of air from a dental unit air syringe was used to generate the air stream . The desensitizing agents were applied according to manufacturers ' guidelines . Sensitivity measurements were recorded at baseline , immediately after treatment , at 1 week , 1 month , and at 3 months . VAS pain scores were analyzed using a repeated measures ANOVA ( alpha = 0.05 ) . RESULTS The pre-polymerized resin suspension ( Pain-Free ) , the fluoride-containing solution ( DentinBloc ) , and the placebo all decreased dentin sensitivity . No significant difference was found among the desensitizing agents at any time period ( P > 0.05 ) PURPOSE Dentine hypersensitivity is one of the most frequently recorded complaints of dental discomfort . Current evidence implicates patent dentinal tubules in hypersensitive dentine , and it follows that one effective way to reduce dentine sensitivity is to occlude the dentinal tubules . The purpose of this study was to compare the efficacy of two different desensitising agents , Cervitec varnish and Gluma varnish . MATERIAL S AND METHODS Two hundred fifty patients self-reporting dentine hypersensitivity completed the paired split mouth r and omised , subject-blind study . Each participant had a minimum of two sensitive teeth in at least two different quadrants and displaying a response of ≥3 cm to an evaporative stimulus . The hypersensitivity levels were measured with a tactile stimulus ( scratchometer ) , thermal stimulus ( cold water test ) , and an evaporative stimulus ( air blast test ) using a visual analogue scale . The teeth were evaluated immediately after treatment , and at 4 and 12 weeks after application of the chlorhexidine-containing varnish Cervitec and the glutaraldehyde-containing varnish , Gluma Desensitizer . RESULTS Statistical analysis indicated that both the desensitising varnishes were effective in alleviating dentine hypersensitivity at all time intervals compared to baseline . There was a highly statistically significantly greater reduction in dentine hypersensitivity to evaporative stimulus , cold stimulus , and tactile stimulus after application of Cervitec than after Gluma Desensitizer ( P < 0.001 ) . CONCLUSION Both the varnishes have a therapeutic potential to alleviate dentine hypersensitivity at all time intervals compared to baseline . However , Cervitec varnish is more efficacious in reducing dentine hypersensitivity than Gluma varnish at both 4 weeks and 12 weeks post-treatment BACKGROUND To evaluate the immediate efficacy in the reduction of dentine hypersensitivity ( DH ) when applying an 810 nm diode laser ( DL ) , and a 10 % potassium nitrate bioadhesive gel ( NK10 % ) . MATERIAL AND METHODS Forty-five consecutive periodontal maintenance patients of both sexes , with a DH > or= 2 on the verbal rating scale ( VRS ) in one or more teeth , were r and omly allocated into three equal groups : 15 patients received DL and placebo gel ; 15 patients were tested with a placebo laser and NK10 % ; and the remaining 15 received a placebo laser and placebo gel . The DH was evaluated at the start of the study , 15 and 30 min . after the laser application , and on days 2 , 4 , 7 , 14 , 30 and 60 by a blind examiner . RESULTS After 15 min . , observations showed a reduction in DH after an evaporative stimulus ( ES ) of 36.9 % ( 0.86 ) , three times greater than that of the control group ( 0.23 ) ( p=0.008 ) . After 14 days , this effect was even greater [ DL 71.7 % (1.67)/NK10 % 36.3 % (1.73)/control 28.1 % ( 0.73 ) ; p=0.004 ] , and lasted until day 60 [ 65.7 % (1.53)/30.4 % (0.73)/25.8 % ( 0.67 ) ; p=0.01 ] . CONCLUSIONS The DL and NK10 % gel were proven effective in the treatment of DH . A significantly greater immediate response was observed with DL AIM To evaluate the effectiveness of four topical desensitizing agents in providing short-term relief of dentin hypersensitivity . METHODS AND MATERIAL S One hundred sixteen hypersensitive teeth with a positive response to intraoral testing for dentin hypersensitivity were included in this study . The four desensitizing agents tested were Duraphat , 2 % fluoride iontophoresis , copal varnish ( CV ) , and Gluma Comfort Bond Plus Desensitizer . Following a specific regimen r and omly determined desensitizing agents were applied in an alternating order when patients presented in a clinical setting with a complaint of hypersensitive teeth . A visual analogue scale was used to determine the degrees of hypersensitivity at three points in time . The first being just before the treatment to establish a baseline , then at 24 hours post-treatment , and the last at seven days post-treatment . Differences in the mean pain scores ( MPS ) between the baseline and post-treatment evaluation periods were used to determine the reduction in dentin hypersensitivity . RESULTS At baseline the MPS for teeth treated with CV was 5.34 ( SD : 2.39 ) , Duraphat was 4.66 ( SD : 1.82 ) , Gluma was 6.03 ( SD : 2.37 ) , and iontophoresis was 5.76 ( SD : 1.37 ) . At 24 hours post-treatment the MPS for CV was 2.1 ( SD : 0.95 ) , Duraphat was 1.38 ( SD;1.86 ) , Gluma was 0.79 ( SD;1.45 ) , and iontophoresis was 1.62 ( SD1.97 ) . The reduction in dentin hypersensitivity at 24 hours ( difference between baseline MPS and 24 hour MPS ) was 5.28 for Gluma , 4.14 for iontophoresis , 3.28 for Duraphat , and 3.24 for CV which were all statistically significant ( p<0.05 ) . At seven days , the MPS for CV was 1.55 ( SD : 1.44 ) , Duraphat was 1.0 ( SD;1.89 ) , Gluma was 0.10 ( SD;0.44 ) , and iontophoresis was 0.3 ( SD;0.98 ) . Reduction of hypersensitivity between 24 hours and one week was 1.32 for iontophoresis , 0.69 for Gluma , 0.55 for CV , and 0.38 for Duraphat . Only the reductions for iontophoresis and Gluma were statistically significant at seven days ( p<0.05 ) . CONCLUSIONS All agents caused a statistically significant reduction in dentin hypersensitivity within 24 hours of treatment . Gluma performed best at 24 hours while iontophoresis appeared to have an edge at seven days . Long-term studies are needed to determine why this difference exists . Dentin hypersensitivity presents as an emergency condition requiring an effective means of providing immediate relief in the clinician 's treatment armamentarium The aim of this study was to evaluate the effect of an ozone delivery system ( HealOzone ; KaVo , Biberach , Germany ) in reducing dentin hypersensitivity . An 8-week , 3-visit , triple-blinded , r and omized controlled clinical trial with 2 HealOzone machines ( ozone/air ) involving 44 subjects was conducted . The pain in response to tactile stimulus or desiccation was assessed by using a 100-mm visual analogue scale . Also , the global subjects ' perception of sensitivity was assessed at each visit by using the visual analogue scale . No subjects reported an increase in pain or any adverse effect . All subjects reported a clinical ly significant reduction of pain at each follow-up relative to baseline ; however , the difference between the study groups was not statistically significant . The effect of treatment of hypersensitive teeth with ozone reduces the pain sensation , but this effect can not be distinguished from the placebo treatment . There was a large placebo effect that narrowed the range over which to detect treatment differences The purpose of this r and omized , clinical , double-blind short-term trial was to evaluate the efficacy of a new lacquer containing a new component ( phosphonic acid methacrylate ) design ed for treating dentine hypersensitivity . Eighty-eight patients participated in this study . At the first visit one tooth was treated with the lacquer ( 1 ) , while another tooth was treated with a placebo ( 2 ) . Sensitivity levels were determined before treatment as well as after one week . An air blast stimulus and a visual analogue scale were used for evaluation . At baseline , the mean hypersensitivity score of group 1 ( 53.2+/-26.3 ) was comparable to the mean hypersensitivity score of the teeth in group 2 ( 53.3+/-24.4 ) . After one week , a significant reduction of the mean hypersensitivity scores ( p < 0.001 ; t-test ) was revealed in group 1 ( 25.8 + /-26.6 ) as well as in group 2 ( 26.4+/-25.3 ) . The difference between the two treatment groups was not significant ( p = 0.7 ) . There is either no difference between the two treatment modalities or the placebo response and /or the time effect was so strong that the treatment efficacy of the new lacquer was hidden by these effects BACKGROUND This subject-blind r and omized clinical trial tested the efficacy of a new 5 percent sodium fluoride varnish ( AllSolutions Fluoride Varnish , Dentsply Professional , York , Pa. ) for treatment of cervical dentin hypersensitivity . The authors also compared the test varnish with a control fluoride varnish ( Duraphat , Colgate Oral Pharmaceuticals , New York City ) . METHODS The study involved application of the test or control varnish to 19 subjects ( 59 teeth ) with tooth sensitivity . The authors applied each product once to each tooth , following manufacturers ' instructions . They used a visual analog scale ( VAS ) to assess subjects ' responses to compressed air and ice stimuli at six weeks before baseline , at baseline and at two , eight and 24 weeks after treatment . RESULTS Mean VAS scores for teeth receiving the test varnish dropped from 34.9 ( air ) and 68.0 ( ice ) at baseline to 26.3 ( air ) and 54.7 ( ice ) at two weeks after treatment . Mean scores at 24 weeks were 20.6 ( air ) and 34.8 ( ice ) , representing statistically significant differences from baseline values . For the control varnish , mean VAS scores dropped from 36.9 ( air ) and 64.2 ( ice ) at baseline to 32.9 ( air ) and 47.2 ( ice ) at two weeks , and to 20.8 ( air ) and 40.3 ( ice ) at 24 weeks . The authors analyzed the data for statistical significance , accounting for clustering of teeth within subjects . CONCLUSION AND CLINICAL IMPLICATION S The test varnish was effective in reducing cervical dentin hypersensitivity . However , the efficacy was not significantly different from that of the control varnish In a well-controlled , double-blind , parallel study design using burnishing with 33 % sodium fluoride paste and " sham " burnishing with a placebo paste , both a cold air stimulus method and an electrical stimulus method can discriminate between levels of dentinal hypersensitivity . Correlation between the scores obtained by the methods was significant . The electrical stimulus method discriminated between the sodium fluoride and placebo effects to a greater degree than did the cold air method . Use of these methods should broaden the scientific foundation and rationale for evaluating the condition of dentinal hypersensitivity and the agents design ed for treatment of persons with this condition OBJECTIVE Compare clinical effectiveness of sodium bicarbonate and bioactive glass powders used for dental prophylaxis . METHODS 25 patients were allocated to either good or poor oral hygiene subgroups ( n=50 ) . Using a double-blind , split-mouth model , all patients underwent prophylaxis treatment on m and ibular teeth ; maxillary teeth were untreated controls . Bioactive glass ( Sylc , OSspray Ltd. , UK ) and sodium bicarbonate ( Prophy Jet , Dentsply , UK ) were applied r and omly to opposite sides of each mouth . Sensitivity to cold air/ethyl chloride , dental shade change and procedural comfort were measured . All parameters were recorded immediately pre- and post-treatment and at 10-day recall . RESULTS Bioactive glass air-polishing , in both subgroups , reported a 44 % ( 0.80+/-0.10 , p<0.05 ) decrease in dental sensitivity , against controls , immediately after application , and a 42 % ( 0.85+/-0.05 , p<0.05 ) decrease at 10-day recall when stimulated with cold air . Ethyl chloride stimulation showed a 10 % ( 3.05+/-0.17 , p<0.05 ) and 22 % ( 2.64+/-0.33 , p<0.05 ) reduction in sensitivity immediately post-op and at 10-day recall . Application of sodium bicarbonate powders increased sensitivity , 17 % ( 1.76+/-0.3 , p<0.05 ) , at 10 days when stimulated with cold air . Both powders showed variation between subgroups in colour change , bioactive glass powder 1 and 4 shades whiter , sodium bicarbonate 1 and 2 shades whiter in good and poor oral hygiene groups , respectively . Patients in both subgroups reported a 46 % ( 7.9+/-1.4 , p<0.05 ) increase in comfort of procedure with the bioactive glass over that when using sodium bicarbonate . CONCLUSIONS Bioactive glass air-polishing was more clinical ly and statistically effective at desensitising both good and poor oral hygiene groups , and removing stain in the poor oral hygiene patient subgroup . Bioactive glass also provided better overall patient comfort during the procedure AIM A r and omised clinical trial was design ed to compare the immediate efficacy ( 48 - 96 h ) of two treatments with bioadhesive gels with different concentrations of potassium nitrate ( NK 5 % versus NK 10 % ) on dentine hypersensitivity ( DH ) . We evaluated DH by means of the use of the evaporative stimulus ( ES ) , as the main outcome , using a placebo control group as reference . PATIENTS AND METHODS Forty-five consecutive patients who , after stimulation with a blast of air , had at least one tooth with DH > or = 2 according to the verbal ratings scale ( VRS ) scale were selected . They were r and omly treated with a bioadhesive gel with 5 % NK , 10 % NK or a placebo gel without NK . The DH was evaluated at baseline , days 2 , 4 , 7 and 14 by an examiner blind to the procedure . The response to the ES with a blast of air , to the tactile stimulation with a probe and the subjective evaluation of the patient measured on the VRS scale were recorded . Statistical analysis was made using the Kruskal-Wallis test . RESULTS A greater reduction of DH after ES was observed after 48 h of treatment in the NK10 % group ( 35.8 % ) compared to the NK5 % group and placebo group ( 11.8 % and 13.4 % , respectively ) . This difference increased significantly at 96 h ( p=0.003 ) . No significant differences were observed for the other variables . These preliminary results may support the usefulness of an NK 10 % gel to reduce the DH after stimulation with a blast of air during the first 4 days of its appearance Dentine hypersensitivity ( DH ) is a painful condition and is a clinical challenge due to the different treatment strategies available . High-intensity lasers have been studied as a possible option . The aim of this r and omized , controlled , double-blind clinical study was to evaluate the effects of Er : YAG and Er , Cr : YSGG lasers on DH . The study group comprised 28 subjects who met the inclusion criteria . A visual analogue scale was used to quantify sensitivity before treatment as baseline , immediately before and immediately after treatment , and 1 week and 1 month after treatment . Teeth were assigned to four groups : group 1 control ( no treatment ) , group 2 Er : YAG laser treatment ( 2 Hz/32.4 mJ/5.9 J/cm2 ) , group 3 Er , Cr : YSGG laser treatment ( 0.25 W/4.4 J/cm2 ) , and group 4 Er , Cr : YSGG laser treatment ( 0.50 W/ 8.9 J/cm2 ) . Data were collected and su bmi tted to statistical analysis for both evaporative ( air ) and mechanical ( probe ) stimulation . For both the air and probe stimulation no differences were observed between the pretreatment sensitivities . With the evaporative stimulus , the pain level immediately after treatment was reduced ; however , after this the values remained stable . Irradiation with the Er : YAG laser was associated with the lowest level of pain . With the mechanical stimulus , group 4 showed the most pronounced decrease in pain immediately after treatment ; however , by the end of the study , pain levels had increased . Groups 1 , 2 and 3 showed a reduction in pain that was significantly different from that in group 4 after the 4 weeks of clinical follow up . Based on the results and within the limits of this study , it can be concluded that none of the laser treatments studied was capable of completely eliminating pain , but the Er : YAG and Er , Cr : YSGG lasers are suitable for the treatment of DH This study investigated the use of iontophoresis in altering the sensitivity level of teeth that displayed thermal and tactile hypersensitivity . A total of 95 teeth were treated with an iontophoresis instrument . Forty-eight of these teeth were treated with a placebo of deionized water , and 47 were treated with a 2 % sodium fluoride solution . Two of the 47 teeth receiving sodium fluoride had identical pretreatment and posttreatment sensitivity ratings , while 40 teeth ( 85.1 % ) demonstrated a reduction in sensitivity . Twenty-nine of the 48 teeth receiving the placebo demonstrated no change in sensitivity . All teeth receiving the placebo were re-treated with sodium fluoride . Forty-seven ( 97.9 % ) responded with reduced levels of sensitivity The aim of this prospect i ve clinical pilot study was to evaluate the pain alleviation effectiveness of two desensitizing agents ( VivaSens and Seal&Protect ) on 30 patients suffering from cervical dentine sensitivity ( CDS ) over a six month period . Analysis of possible differences in pain alleviation effect between the agents and over time was performed . Further , the experienced pain was registered in a question naire regarding to what extent the treatment improved oral health/life quality among the patients . The patients ( 23 female , 7 male ) were r and omly divided into two groups . Each group was treated with one of the two desensitizing agents . Sensitivity measurements were recorded before treatment ( baseline ) and after treatment at time points of one week and six months . The patients were asked to rate the sensitivity experienced in the area during air stimulation by marking on a Visual Analogue Scale ( VAS ) . At six months , 27 patients ( 90 % ) had completed the clinical trial . The results showed that a significant reduction of CDS was achieved by using VivaSens or Seal&Protect after both one week and six months . However , there were no differences found on treatment effects between the two desensitizing agents . The results from the question naire showed that the patients experienced improved oral health/life quality when comparing the status before and after treatment ( 0.000 < or = p < or = 0.0021 ) and there were no statistically significant difference in treatment effects between the products . In conclusion , both desensitizing agents were effective in relieving cervical dentin hypersensitivity during the time course of the study as evaluated both by air stimulation and a question naire related to oral health/ quality of life status AIM The aim of the present study was to evaluate and compare the desensitizing effects of an Er : YAG laser ( KEY II(R ) , KaVo , Germany ) and Dentin Protector ( Vivadent , Germany ) on cervically exposed hypersensitive dentine . METHOD A group of 30 patients showing a total of 104 contralateral pairs of hypersensitive and caries-free teeth was selected and r and omly allocated in a split-mouth design to either ( 1 ) Er : YAG laser ( 80 mJ/pulse , 3 Hz ) , or ( 2 ) the application of Dentin Protector ( polyurethane-isocyanate 22.5 % ; methylenechloride 77.5 % ) whereat one pair served as an untreated control in each patient . The degree of sensitivity to a thermal stimulus was determined qualitatively with an evaporative stimulus defined as a 3-s air blast at a distance of 2 mm from each site to be tested . A qualitative registration of the degree of discomfort was determined according to an arbitrary pain scale in 4 degrees . Recordings were assessed before treatment , immediately after , 1 week , 2 and 6 months after treatment by 1 blinded examiner . RESULTS Both treatment forms result ed in significant improvements of discomfort immediately after and 1 week post treatment . After 2 months , the discomfort in the Dentin Protector(R ) group increased up to 65 % of the baseline score and even up to 90 % after 6 months , whereas the effect of the laser remained at the same level that was achieved immediately after treatment . The differences immediately after , 1 week , 2 and 6 months post treatment between both groups were statistically high significant ( p < or = 0.001 ; respectively ) . Compared to the untreated control group , both treatment forms result ed in a significant reduction of discomfort at each follow-up examination . CONCLUSION It was concluded that desensitizing of hypersensitive dentine with an Er : YAG laser is effective and the maintenance of the positive result was more prolonged than with Dentin Protector & NA ; After a pilot study had indicated that the topical application of guanethidine might be of value in the treatment of tooth dentine hypersensitivity , a double‐blind study was undertaken to investigate whether guanethidine was more effective than a distilled water control in alleviating dentinal pain . In 39 adult subjects , who had complained of dentine hypersensitivity , a 1 sec blast of air from a dental 3‐in‐1 syringe was directed onto sensitive root dentine at an angle of 90 ° from a distance of 1 cm . The severity of the result ing pain was indicated by the subject on a 10 cm visual analogue scale ( VAS ) . One droplet of either 1 % guanethidine monosulphate ( Ismelin , Ciba‐Geigy ) or distilled water , allocated at r and om , was applied to the dentine for 1 min . The tooth was re‐tested with the st and ardised air blast and a second VAS was marked by the subject . In total , 19 patients received guanethidine and 20 received water . VAS scores before treatment in the 2 groups treated with either guanethidine or water ( means : 6.5 ± 2.2 and 6.0 ± 2.5 , respectively ) were not significantly different ( Mann‐Whitney , P = 0.48 ) whereas the VAS scores in the 2 groups after treatment with guanethidine or water ( means : 2.7 ± 2.4 and 4.8 ± 2.9 , respectively ) were significantly different ( Mann‐Whitney , P < 0.02 ) . It was concluded that guanethidine reduced dentinal hypersensitivity more effectively than distilled water . Within‐group comparison of the pre‐ and post‐treatment VAS scores , using the Wilcoxon matched‐pairs test , showed that distilled water had also produced a significant improvement ( P < 0.01 ) , probably attesting the operation of a placebo effect ; the improvement produced by guanethidine reached a greater level of significance ( P < 0.001 ) . This beneficial analgesic action of guanethidine may offer a novel , simple method of relieving the discomforts of dental conservation and restoration and lead to a better underst and ing of the hitherto obscure aetiology of dentinal pain The aim of this study was to evaluate in vivo the use of low-level galium-aluminium-arsenide ( GaAlAs ) ( BDP 600 ) laser and sodium fluoride varnish ( Duraphat ) in the treatment of cervical dentine hypersensitivity . Twelve patients , with at least two sensitive teeth were selected . A total of 60 teeth were included in the trial . Prior to desensitizing treatment , dentine hypersensitivity was assessed by a thermal stimulus and patients ' response to the examination was considered to be a control . The GaAlAs laser ( 15 mW , 4 J/cm2 ) was irradiated on contact mode and fluoride varnish was applied at cervical region . The efficiency of the treatments was assessed at three examination periods : immediately after first application , 15 and 30 days after the first application . The degree of sensitivity was determined following predefined criteria . Data were su bmi tted to analysis and no statistically significant difference was observed between fluoride varnish and laser . Considering the treatments separately , there was no significant difference for the fluoride varnish at the three examination periods , and for laser therapy , significant difference ( P < 0.05 ) was found solely between the values obtained before the treatment and 30 days after the first application . It may be concluded that both treatments may be effective in decreasing cervical dentinal hypersensitivity . Moreover , the low-level GaAlAs laser showed improved results for treating teeth with higher degree of sensitivity PURPOSE To determine the efficacy of an in-office desensitizing paste containing 8 % arginine and calcium carbonate relative to that of a commercially-available pumice prophylaxis paste in reducing dentin hypersensitivity instantly after a single application following a dental scaling procedure and to establish the duration of sensitivity relief over a period of 4 weeks and 12 weeks . METHODS This was a single-center , parallel group , double-blind , stratified clinical study conducted in San Francisco , California , USA . Qualifying adult male and female subjects who presented two hypersensitive teeth with a tactile hypersensitivity score ( Yeaple Probe ) between 10 - 50 grams of force and an air blast hypersensitivity score of 2 or 3 ( Schiff Cold Air Sensitivity Scale ) were stratified according to their baseline hypersensitivity scores and r and omly assigned within strata to one of two treatment groups : ( 1 ) A Test Paste , a desensitizing paste containing 8 % arginine and calcium carbonate ( Colgate-Palmolive Co ) ; and ( 2 ) A Control Paste , Nupro pumice prophylaxis paste ( Dentsply Professional ) . Subjects received a professionally-administered scaling procedure , after which they were re-examined for tactile and air blast dentin hypersensitivity ( Post-Scaling Examinations ) . The assigned pastes were then applied as the final step to the professional dental cleaning procedure . Tactile and air blast dentin hypersensitivity examinations were again performed immediately after paste application . Subjects were provided with a commercially-available non-desensitizing dentifrice containing 0.243 % sodium fluoride ( Crest Cavity Protection , Procter & Gamble Co. ) and an adult soft-bristled toothbrush and were instructed to brush their teeth for 1 minute , twice daily at home using only the toothbrush and dentifrice provided , for the next 12 weeks . Subjects returned to the testing facility 4 and 12 weeks after the single application of Test or Control paste , having refrained from all oral hygiene procedures and chewing gum for 8 hours and from eating and drinking for 4 hours , prior to each follow-up visit . Assessment s of tactile and air blast hypersensitivity , and examinations of oral soft and hard tissue were repeated at these 4- and 12-week examinations . RESULTS 68 subjects completed the 12-week study . No statistically significant differences from baseline scores were indicated at the Post-Scaling Examinations for either the Test Paste or Control Paste groups . Immediately following product application and 4 weeks after product application , subjects assigned to the Test Paste group exhibited statistically significant improvements from baseline with respect to baseline-adjusted mean air blast ( 44.1 % and 45.9 % respectively ) and mean tactile hypersensitivity scores ( 156.2 % and 170.3 % respectively ) . At the same time points , subjects assigned to the Control Paste group exhibited statistically significant improvements from baseline with respect to baseline-adjusted mean air blast ( 15.1 % and 8.9 % respectively ) and mean tactile hypersensitivity scores ( 43.1 % and 8.3 % respectively ) . Immediately following application of the assigned paste and 4 weeks later , the Test Paste group demonstrated statistically significant reductions in dentin hypersensitivity with respect to baseline-adjusted mean air blast ( 34.1 % and 40.6 % respectively ) and mean tactile hypersensitivity scores ( 79.0 % and 149.6 % respectively ) , compared to the Control Paste group . No statistically significant differences were exhibited between paste groups at the Post-Scaling and 12-week examinations with respect to mean tactile and baseline-adjusted mean air blast hypersensitivity scores OBJECTIVES In two clinical trials of 8 weeks duration , the ability of a new dentifrice , containing potassium nitrate , stannous fluoride and sodium fluoride to reduce dentine hypersensitivity was compared with either a non-desensitising fluoride dentifrice or a commercially available desensitising dentifrice ( Sensodyne F ) to reduce dentine hypersensitivity . METHOD In both studies , the participants had to have at least two sensitive root surfaces . Subjects were stratified by baseline tactile and air blast sensitivity scores and the number of sensitive teeth and r and omly allocated to 2 balanced groups . In the first study ( N=81 ) the new dentifrice was compared with a fluoride dentifrice and in the second study ( N=105 ) with Sensodyne F. Participants were requested to brush with their assigned dentifrice twice a day for one minute . At 4 and 8 weeks the sensitive teeth were again examined and their tactile and air blast sensitivity scores recorded . RESULTS In study 1 , the group using the new dentifrice tolerated greater pressure after 4 ( 34.9 g ) and 8 weeks ( 38.4 g ) than the group using the fluoride dentifrice ( 22.9 g and 19.0 g , respectively ) . These differences were statistically significant ( p<0.001 ) . At 4 and 8 weeks , the mean air blast scores for the group using the new dentifrice ( 1.39 and 0.83 ) were lower than for the group using fluoride dentifrice ( 1.78 and 1.76 ) and were significantly different at 8 weeks ( p<0.001 ) . In study 2 the group using the new dentifrice tolerated greater pressure after 4 ( 40.5 g ) and 8 weeks ( 43.7 g ) than the group using Sensodyne F ( 27.8 g and 33.2 g , respectively ) . These differences were statistically significant ( p<0.001 ) . At 4 and 8 weeks , the mean air blast scores for the group using the new dentifrice ( 1.10 and 0.67 ) were significantly lower than the group using Sensodyne F ( 1.90 and 1.57 ) ( p<0.001 ) . CONCLUSIONS These studies demonstrate that the new dentifrice , containing potassium nitrate , stannous fluoride and sodium fluoride is significantly better at reducing dentine hypersensitivity than both the dentifrice containing sodium fluoride and the one containing potassium chloride , triclosan and sodium fluoride ( Sensodyne F ) BACKGROUND Dentin hypersensitivity is a common clinical condition and age-old complaint , presenting problems to both the patient and the dentist . Besides causing discomfort , the condition may deter a person from establishing or maintaining adequate oral hygiene procedures , further complicating oral health . The failure to practice satisfactory plaque control has well-established consequences on gingival and periodontal health . Thus , a cycle of sensitive teeth leading to reduced plaque control , more periodontal disease , and more recession may be established . METHODS The hypersensitive teeth were identified by the patient and verified by the light stroke of a dental explorer along the cervical area of all teeth present . Subjects fulfilling the inclusion and exclusion criteria were evaluated using tactile , 1-second air blast , and cold water stimuli , and the subject 's response was recorded on the verbal rating scale . A total of 425 teeth from 50 patients included in this study were r and omly divided into two groups : group 1 , who received 2 % sodium fluoride-iontophoresis ( NaF ) and group 2 , who received an aqueous solution of hydroxy-ethyl-methacrylate and glutaraldehyde ( HEMA-G ) . The teeth were evaluated immediately after treatment and at 2 weeks , 1 month , and 3 months . In case of failure at the 2-week interval , the affected tooth was retreated with the same drug as before and evaluated further . RESULTS The results were statistically analyzed , and it was found that group 1 treatment was more effective than group 2 at 1- and 3-month intervals . There was a comparatively greater recurrence of hypersensitivity in group 2 . A comparable number of teeth required repeat dosage in both groups . Teeth which required repeat dosage had greater mean discomfort scores at baseline for all three tests than the teeth which did not require a repeat dose . CONCLUSIONS Both agents showed significant reduction in sensitivity at all time intervals compared to baseline ; however , NaF had a comparatively greater effect than HEMA-G at both the 1- and 3-month intervals ; an almost equal number of teeth in both groups required repeat doses . Teeth with a higher initial sensitivity score required a repeat dose . Both agents were found to be equally effective immediately after application ; the 2 % NaF was comparatively better than HEMA-G in providing long-term relief PURPOSE To evaluate the clinical efficacy in reducing dentin hypersensitivity of a professional desensitizing paste containing 8 % arginine and calcium carbonate relative to that of a commercially-available pumice prophylaxis paste when applied pre-procedurally to a professional dental cleaning ( dental prophylaxis ) . METHODS This was a single-center , parallel group , double-blind , stratified clinical study , conducted in Langhorne , Pennsylvania . Adult male and female subjects who presented a tactile hypersensitivity score ( Yeaple Probe ) between 10 and 50 grams of force and an air blast hypersensitivity score of 2 or 3 ( Schiff Cold Air Sensitivity Scale ) were stratified according to their baseline hypersensitivity scores and r and omly assigned within strata to one of two treatment groups . The two treatment groups were : ( 1 ) a Test paste , a desensitizing paste containing 8 % arginine and calcium carbonate ( Colgate-Palmolive Co. ) ; and ( 2 ) a Control paste , Nupro pumice prophylaxis paste ( Dentsply Professional ) . Subjects had their assigned paste applied immediately before receiving a professional dental cleaning procedure . After the completion of the dental cleaning procedure , tactile and air blast dentin hypersensitivity examinations were again performed following the same methodology employed for the baseline hypersensitivity examinations . RESULTS 45 subjects completed the study . At the final hypersensitivity examinations , conducted immediately after the completion of the dental cleaning procedure , subjects assigned to the test group exhibited statistically significant improvements from baseline with respect to baseline-adjusted mean tactile ( 132.1 % ) and air blast hypersensitivity scores ( 48.6 % ) . Additionally , subjects assigned to the control group exhibited a statistically significant hypersensitivity improvement from baseline with respect to baseline-adjusted mean air blast hypersensitivity scores ( 13.9 % ) . The hypersensitivity improvement from baseline indicated for the control group for mean tactile hypersensitivity scores ( 21.7 % ) was not statistically significant . At the final hypersensitivity examinations , statistically significant differences were indicated between the test group and the control group with respect to baseline-adjusted mean tactile ( 110.0 % ) and air blast hypersensitivity scores ( 41.9 % ) Tooth sensitivity is a common clinical problem . This multi-center r and omized clinical trial assessed the effectiveness and safety of topical diammine silver fluoride . From two sites ( Lima and Cusco , Peru ) , 126 adults with at least one tooth sensitive to compressed air were r and omly assigned to either the experimental treatment or sterile water , and pain was assessed by means of a 100-mm visual analogue scale at 24 hours and 7 days . The diammine silver fluoride reduced pain at 7 days at both sites . At the Lima site , the average change in pain scores between baseline and day 7 for the silver fluoride group was -35.8 ( SD = 27.7 ) mm vs. 0.4 ( SD = 16.2 ) mm for the control group ( P < 0.001 ) . In Cusco , the average change in pain scores for the silver fluoride group was −23.4 ( SD = 21.0 ) mm and -5.5 ( 18.1 ) mm for the control group ( P = 0.002 ) . No tissue ulceration , white changes , or argyria was observed . A small number of participants in the silver fluoride group experienced a mild but transient increase in erythema in the gingiva near the tooth . No changes were observed in the Gingival Index . We concluded that diammine silver fluoride is a clinical ly effective and safe tooth desensitizer |
12,126 | 24,034,489 | From these observational studies , the summary estimates suggest that oseltamivir may reduce mortality , hospitalisation and duration of symptoms compared with no treatment .
Inhaled zanamivir may also reduce symptom duration and hospitalisations , but patients may experience more complications compared with no treatment .
Earlier treatment with antivirals is generally associated with better outcomes than later treatment . | Despite the use of antivirals to treat patients with severe influenza , questions remain with respect to effects and safety . | OBJECTIVE To compare the effectiveness of zanamivir with oseltamivir for influenza A and B. METHODS 1113 patients with influenza A or B were enrolled in the 2006 - 2007 influenza season . The duration of fever ( temperature , > or=37.5 degrees C ) and the percentage of patients afebrile at 24 and 48 h after the first dose of zanamivir or oseltamivir were calculated . Virus persistence after zanamivir therapy was also evaluated . RESULTS There were marginally significant differences between the duration of fever after the first dose of zanamivir ( 31.8+/-18.4h ) and oseltamivir ( 35.5+/-23.9h ) for influenza A ( p<0.05 ) . The duration of fever after starting zanamivir therapy ( 35.8+/-22.4h ) was significantly shorter than that of oseltamivir ( 52.7+/-31.3h ) for influenza B ( p<0.001 ) . There were no significant differences between influenza A and B in the percentage of patients afebrile at 24 or 48 h after the first inhalation of zanamivir . The reisolation rate after zanamivir therapy showed marginally significant differences between influenza A and B ( < 0.05 ) . By multiple regression analysis , therapy ( zanamivir or oseltamivir ) was the major determinant affecting the duration of fever for influenza B. CONCLUSION Zanamivir therapy is more effective than oseltamivir for the treatment of influenza B infection Background —Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes . Oseltamivir , a treatment for influenza , has been shown to decrease the severity of an influenza episode , but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease . Methods and Results —Electronic healthcare service and pharmacy records for 37 482 TRICARE beneficiaries , aged 18 and older , with a coded history of cardiovascular ( CV ) disease and a subsequent diagnosis of influenza from October 1 , 2003 , through September 30 , 2007 , were examined . Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis . The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5 % and 21.2 % , respectively ( P<0.005 ) . Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes . After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model , a statistically significant protective effect was associated with oseltamivir treatment ( odds ratio , 0.417 ; 95 % CI , 0.349 to 0.498 ) . Conclusions —Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease . These findings merit confirmation in further prospect i ve and controlled studies . Meanwhile , in patients with CV disease , strict adherence with current practice guidelines for prevention and treatment of influenza is recommended Background The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza . Methods A prospect i ve , observational cohort study was conducted over 24 months ( 2007–2008 ) in two acute , general hospitals . Consecutive , hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established ( based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol ) . Outcomes studied included in-hospital death , length of stay and duration of oxygen therapy . Factors affecting outcomes were analysed using multivariate Cox proportional hazards models . Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates . Results 754 patients were studied ( influenza A , n=539 ; > 75 % H3N2 ) . Their mean age was 70±18 years ; co-morbidities and serious complications were common ( 61–77 % ) . Supplemental oxygen and ventilatory support was required in 401 ( 53.2 % ) and 41 ( 5.4 % ) patients , respectively . 39 ( 5.2 % ) patients died ; pneumonia , respiratory failure and sepsis were the causes . 395 ( 52 % ) patients received antiviral ( oseltamivir ) treatment . Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results . The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients , respectively ; among those with co-morbidities , it was 5.62 and 11.64 per 1000 patient-days , respectively . In multivariate analysis , antiviral use was associated with reduced risk of death ( adjusted HR ( aHR ) 0.27 ( 95 % CI 0.13 to 0.55 ) ; p<0.001 ) . Improved survival was observed with treatment started within 4 days from onset . Earlier hospital discharge ( aHR 1.28 ( 95 % CI 1.04 to 1.57 ) ; p=0.019 ) and faster discontinuation of oxygen therapy ( aHR 1.30 ( 95 % CI 1.01 to 1.69 ) ; p=0.043 ) was associated with early treatment within 2 days . Few ( n=15 ) H1N1 isolates in this cohort had the H275Y mutation . Conclusions Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes Oseltamivir has been used for treatment of influenza A and B infections , but recent reports documented that it was less active against the latter . We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan . Among 1,848 patients screened , 299 influenza A and 209 influenza B patients were administered oseltamivir ( treated groups ) , and 28 influenza A and 66 influenza B patients were assigned as non-treated groups . The duration of fever , defined as period when patients had the maximum temperature higher than 37.5 degrees C in three-time measurements in a day after the clinic visit , was evaluated among the four groups . In uni-variate analysis , the duration of fever was shorter for treated group than non-treated for influenza A ( 1.8 + /- 0.9 days vs 2.6 + /- 1.3 days , p < 0.01 ) , but it was not significant for influenza B ( 2.4 + /- 1.3 days vs 2.8 + /- 1.2 days , p = 0.9 ) . The fever duration was longer in treated influenza B than A patients ( p < 0.01 ) . Multi-variate analysis indicated younger age ( < 6 years old ) and higher body temperature at the clinic visit prolonged the duration of fever . Adjusted average duration of fever indicated that oseltamivir was effective for both types , but more effective on influenza A , and the benefit increased for younger children . Our data provide evidence that oseltamivir is beneficial for influenza infections , but the effectiveness is differed by type and age BACKGROUND To compare the effectiveness of oseltamivir for treatment of influenza A and influenza B , we conducted a prospect i ve , multicenter study of the 2003 - 2004 and 2004 - 2005 influenza seasons . The study included 3351 patients in whom influenza had been diagnosed by use of an antigen detection test kit . METHODS Oseltamivir was administered to 1818 patients with influenza A and 1485 patients with influenza B. No anti-influenza drugs were administered to 21 patients with influenza A or to 27 patients with influenza B. Patients receiving oseltamivir therapy were divided into 4 groups according to the time between the onset of fever ( temperature , > or = 37.5 degrees C ) and administration of the first dose of oseltamivir ( 0 - 12 h , 13 - 24 h , 25 - 36 h , and 37 - 48 h ) . The patients were also divided into 4 subgroups on the basis of age ( 0 - 6 years , 7 - 15 years , 16 - 64 years , and > 64 years ) . Virus isolation was performed after completion of oseltamivir therapy for 44 patients with influenza A and 31 patients with influenza B. RESULTS The duration of fever was significantly shorter for patients with influenza A and B who were treated with oseltamivir than for patients who were not treated with an anti-influenza drug ( P<.001 for both ) . The time until the patient became afebrile after the initial administration of oseltamivir and the duration of fever were significantly longer for patients with influenza B than for patients with influenza A for the 0 - 12 h , 13 - 24 h , 25 - 36 h , and 37 - 48 h groups ( P<.001 ) and for all age groups ( P<.001 ) . After 4 - 6 days of oseltamivir therapy , the influenza B virus reisolation rate ( 51.6 % ) was significantly higher than the influenza A virus reisolation rate ( 15.9 % ) ( P<.001 ) . CONCLUSION Oseltamivir is less effective for influenza B than for influenza A with regard to duration of fever and virus persistence , irrespective of patient age or the timing of administration of the first dose Summary : Respiratory viruses ( RVs ) frequently cause severe respiratory disease in bone marrrow transplant ( BMT ) recipients . To evaluate the frequency of RV , nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection ( URI ) . Direct immunofluorescence assay was performed for respiratory syncytial virus ( RSV ) , influenza ( Flu ) A and B , adenovirus and parainfluenza ( Paraflu ) virus . Patients with RSV pneumonia or with upper RSV infection , but considered at high risk for developing RSV pneumonia received aerosolized ribavirin . Oseltamivir was given to patients with influenza . A total of 179 patients had 392 episodes of URI . In all , 68 ( 38 % ) tested positive : RSV was detected in 18 patients ( 26.4 % ) , Flu B in 17 ( 25 % ) , Flu A in 11 ( 16.2 % ) and Paraflu in 7 ( 10.3 % ) . A total of 14 patients ( 20.6 % ) had multiple RV infections or coinfection . RSV pneumonia developed in 55.5 % of the patients with RSV-URI . One of the 15 patients ( 6.6 % ) with RSV pneumonia died . Influenza pneumonia was diagnosed in three patients ( 7.3 % ) . RSV and influenza infections peaked in fall – winter and winter – spring months , respectively . We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia . The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in r and omized trials Abstract Background The goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza Methods This was a 1-year prospect i ve , observational study involving consecutive adults hospitalized with influenza . Nasal and throat swabs were collected at presentation , then daily until 1 week after symptom onset . Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed . Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models Results One hundred forty-seven in patients with influenza A ( H3N2 ) infection were studied ( mean age ± st and ard deviation , 72±16 years ) . Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched out patients ( control subjects ) . Patients with major comorbidities had high viral RNA concentration even when presenting > 2 days after symptom onset ( mean ± st and ard deviation , 5.06±1.85 vs 3.62±2.13 log10 copies/mL ; P=.005 ; β , + 0.86 [ 95 % confidence interval , + 0.03 to + 1.68 ] ) . Viral RNA concentration demonstrated a nonlinear decrease with time ; 26 % of oseltamivir-treated and 57 % of untreated patients had RNA detected at 1 week after symptom onset . Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration ( mean β [ st and ard error ] , −1.19 [ 0.43 ] and −0.68 [ 0.33 ] log10 copies/mL for patients treated on day 1 and days 2–3 , respectively ; P<.05 ) and viral RNA clearance at 1 week ( odds ratio , 0.10 [ 95 % confidence interval , 0.03–0.35 ] and 0.30 [ 0.10–0.90 ] for patients treated on day 1–2 and day 3–4 , respectively ) . Conversely , major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance . Viral RNA clearance was associated with a shorter hospital stay ( 7.0 vs 13.5 days ; P=.001 ) Conclusion Patients hospitalized with severe influenza have more active and prolonged viral replication . Weakened host defenses slow viral clearance , whereas antivirals started within the first 4 days of illness enhance viral BACKGROUND We conducted a prospect i ve cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario , Canada . METHODS Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study . Demographic and medical data were collected by patient and physician interview and chart review . The main outcome evaluated was death within 15 days after symptom onset . RESULTS Data were available for 512 of 541 eligible patients . There were 185 children ( < 15 years of age ) , none of whom died and none of whom were treated with antiviral drugs . The median age of the 327 adults was 77 years ( range , 15 - 98 years ) , 166 ( 51 % ) were male , 245 ( 75 % ) had a chronic underlying illness , and 216 ( 71 % ) had been vaccinated against influenza . Of the 327 adult patients , 184 ( 59 % ) presented to the emergency department within 48 h after symptom onset , 52 ( 16 % ) required intensive care unit admission , and 27 ( 8.3 % ) died within 15 days after symptom onset . Most patients ( 292 patients ; 89 % ) received antibacterial therapy ; 106 ( 32 % ) were prescribed antiviral drugs . Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality ( odds ratio , 0.21 ; 95 % confidence interval , 0.06 - 0.80 ; n=100 , 260 ) . There was no apparent impact of antiviral therapy on length of stay in survivors . CONCLUSIONS There is a significant burden of illness attributable to influenza in this highly vaccinated population . Treatment with antiviral drugs was associated with a significant reduction in mortality From January 2001 to July 2002 , we investigated the duration of fever , the duration of hospitalization , the frequency of antipyretic use , and other clinical symptoms of 162 in patients with influenza A virus infection , and compared them with oseltamivir-treated , amantadine-treated , and untreated groups . The duration of fever and the duration of hospitalization treated were significantly shortened in the oseltamivir-treated group than in the amantadine-treated group and untreated group . There was no difference in the duration of fever between patients treated by oseltamivir at 2 mg/kg/day and those at 4 mg/kg/day . The frequency of antipyretic use was lower in the oseltamivir-treated group than in the other group . No difference was observed in the duration of fever and the frequency of antipyretic use between patients treated by oseltamivir with antibiotics and those by oseltamivir alone . The complications such as vomiting , abdominal pain , irritability were observed in 9 % of patients treated by oseltamivir . But those symptoms were not serious , and the rate of complications in the oseltamivir-treated group was lower than that in untreated group . In conclusion , oseltamivir is safe and effective in the treatment of influenza virus infection in children , and it may reduce the amount of antibiotics and antipyretic use BACKGROUND To evaluate the effectiveness of oseltamivir and amantadine for the treatment of influenza with respect to various clinical factors , a prospect i ve multicenter study of the influenza season of 2002 - 2003 was done with 2163 patients whose condition was diagnosed by an antigen-detection test kit . METHODS Oseltamivir was administered to 803 patients with influenza A ( A+Os group ) and 684 patients with influenza B ( B+Os group ) . Amantadine was administered to 676 patients with influenza A ( A+Am group ) . RESULTS For each group , the duration of fever ( i.e. , body temperature , > or = 37.5 degrees C ) was significantly shorter in patients who received the drug within 12 h after the onset of symptoms than in patients who received the drug > 12 h after the onset . For all 3 groups , the duration of fever was shorter in patients with a highest temperature < 39 degrees C than in patients with temperatures > or = 39 degrees C. The duration of fever was significantly longer for the B+Os group than for the A+Os group . Multiple regression analysis found that the type of influenza , the highest body temperature , and the time between the onset of symptoms and the start of treatment are independent factor that influence the duration of fever . CONCLUSIONS Early administration increases the benefit of anti-influenza drugs -- not only the benefit of oseltamivir treatment for influenza A , but also the benefit of amantadine treatment for influenza A and oseltamivir treatment for influenza B. Oseltamivir may be less effective as a treatment for influenza B than for influenza A. A highest body temperature of > or = 39 degrees C was an indicator of a longer duration of fever |
12,127 | 28,438,211 | Meta-analyses showed significant improvement in general health , mental health , physical function and environment domains of quality of life among intervention groups .
Conclusions Although the available evidence suggests that existing social and behavioral interventions can improve some quality of life domains , the quality of evidence was insufficient to support the notion that these interventions can improve the overall quality of life of HIV infected people receiving ART . | Background Improvement in quality of life is crucial for HIV infected people .
Social and behavioral interventions have been implemented in different context s to improve the quality of life among HIV infected people .
This review appraises the evidence for available interventions that focused on quality of life of HIV infected people receiving antiretroviral therapy ( ART ) . | To determine whether MBSR groups would help gay men living with HIV improve psychosocial functioning and increase mindfulness compared to treatment-as-usual ( TAU ) . Methods : 117 participants were r and omized 2:1 to MBSR or TAU . No new psychosocial or psychopharmacological interventions were initiated within 2 months of baseline . St and ardized question naires were administered pre- , postintervention and at 6 months . An intent-to-treat analysis found significant benefits of MBSR : at post-intervention and 6 months follow up , MBSR participants had significantly lower avoidance in IES and higher positive affect compared to controls . MBSR participants developed more mindfulness as measured by the Toronto Mindfulness Scale ( TMS ) including both TMS subscales , curiosity and decentering , at 8-week and 6 months . For the sample as a whole , increase in mindfulness was significantly correlated with reduction in avoidance , higher positive affect and improvement in depression at 6 months . MBSR has specific and clinical ly meaningful effects in this population Background : AIDS-related bereavement is a severe life stressor that may be particularly distressing to persons themselves infected with HIV . Increasing evidence suggests that psychological health is associated with disease progression , HIV-related symptoms , and mortality . Purpose : This study assessed change in health-related quality of life among HIV+ persons following a group intervention for coping with AIDS-related loss . Methods : The sample included 235 HIV+ men and women of diverse ethnicities and sexual orientations who had experienced an AIDS-related loss within the previous 2 years . Participants were r and omly assigned to a 12-week cognitive-behavioral bereavement coping group intervention or offered individual psychotherapy upon request . Quality of life was assessed at baseline and 2 weeks after the intervention . Results : Participants in the group intervention demonstrated improvements in general health-related and HIV-specific quality of life , while those in the comparison remained the same or deteriorated . Effect sizes indicated that the majority of change occurred in women . Conclusion : This bereavement group aim ed at improving coping with grief also had a positive impact on health-related quality of life among HIV+ men and women , and suggests that cognitive-behavioral interventions may have a broad impact on both emotional and physical health AIMS AND OBJECTIVES This study aim ed to examine the effects of nurse-delivered home visits combined with telephone intervention on medication adherence , and quality of life in HIV-infected heroin users . BACKGROUND Drug use is consistently reported as a risk factor for medication non-adherence in HIV-infected people . DESIGN An experimental , pretests and post-tests , design was used : baseline and at eight months . METHODS A sample of 116 participants was recruited from three antiretroviral treatment sites , and 98 participants completed the study . They were r and omly assigned to two groups : 58 in the experimental group and 58 in the control group . The experimental group received nurse-delivered home visits combined with telephone intervention over eight months , while the control group only received routine care . The question naire of Community Programs for Clinical Research on AIDS ( CPCRA ) Antiretroviral Medication Self-Report was used to assess levels of adherence , while quality of life and depression were evaluated using Chinese versions of World Health Organization Quality of Life Instrument-Abbreviated version ( WHOQOL-BREF ) and Self-rating Depression Scale , respectively . Data were obtained at baseline and eight months . RESULTS At the end of eight months , participants in the experimental group were more likely to report taking 100 % of pills ( Fisher 's exact = 14.3 , p = 0.0001 ) and taking pills on time ( Fisher 's exact = 18.64 , p = 0.0001 ) than those in the control group . There were significant effects of intervention in physical ( F = 10.47 , p = 0.002 ) , psychological ( F = 9.41 , p = 0.003 ) , social ( F = 4.09 , p = 0.046 ) and environmental ( F = 4.80 , p = 0.031 ) domains of WHOQOL and depression ( F = 5.58 , p = 0.02 ) . CONCLUSIONS Home visits and telephone calls are effective in promoting adherence to antiretroviral treatment and in improving the participants ' quality of life and depressive symptoms in HIV-infected heroin users . RELEVANCE TO CLINICAL PRACTICE It is important for nurses to recognise the issues of non-adherence to antiretroviral treatment in heroin users . Besides st and ard care , nurses should consider conducting home visits and telephone calls to ensure better health outcome of antiretroviral treatment in this population OBJECTIVE We tested the effects of a 10-week group-based cognitive-behavioral stress management/expressive-supportive therapy intervention ( CBSM+ ) and a time-matched individual psychoeducational condition for 330 women with AIDS reporting moderate to poor baseline quality of life ( QOL ) . The goal of this study was to examine treatment effects on total QOL and 11 QOL domains from baseline to post-intervention follow-up . METHODS Participants were assessed at baseline , r and omized to a treatment condition ( individual psychoeducation condition n=180 , group-based CBSM+ condition n=150 ) , participated in the intervention for 10 weeks and assessed again within 4 weeks following the intervention . QOL was measured using the Medical Outcomes Study -HIV-30 . RESULTS QOL scores increased over the course of both interventions for the total QOL score and three QOL domains : cognitive functioning , health distress and overall health perceptions . While women in the CBSM+ group condition showed a significant improvement in mental health QOL from pre- to post-intervention , women in the individual condition did not change . No changes were observed for energy/fatigue , health transition , single-item overall QOL , pain , physical well-being , role functioning or social functioning in either condition . CONCLUSION Results suggest that group-based CBSM+ and individual psychoeducational interventions are effective at improving certain aspects of QOL and that group-based CBSM+ may be particularly effective at increasing QOL related to mental health in this population of women with AIDS CONTEXT Proper adherence is essential to obtain the desired results of antiretroviral therapy ; thus , new interventional strategies for this purpose must be sought . OBJECTIVE Comparison of 2 interventions , one conducted by a health professional and the other by a peer ( patient on antiretroviral therapy ) , to improve adherence to antiretroviral therapy . DESIGN AND SETTING In 2003 , a r and omized , concurrent , follow-up study was conducted at 3 hospitals . PARTICIPANTS Patients were recruited consecutively at infectious disease visits scheduled to monitor their disease from May to September 2003 . A sealed envelope was used to assign patients to each intervention group . A previous phase was conducted to unify data collection , and the intervention consisted of 4 visits at weeks 0 , 8 , 16 , and 24 . RESULTS Among the 240 patients included , 198 completed follow-up , and in 11 of these , treatment was interrupted at the doctor 's decision . At baseline , 46.8 % were classified as adherent . Multilevel analysis showed that as the visits progressed , the probability of adhering to treatment increased ( OR 1.23 ; P<.01 ) . Although differences were not significant , the group treated by a peer showed better results than the group treated by a health professional ( OR 1.60 ; P=0.25 ) . A lower probability of antiretroviral adherence was observed in patients receiving a drug combination including a protease inhibitor ( OR 0.27 ; P<0.01 ) and in those with psychological distress ( OR 0.44 ; P=0.03 ) . Patients with a higher score on the physical quality of life index ( OR 1.05 ; P<0.01 ) presented a higher probability of adherence . CONCLUSIONS The psychoeducational intervention studied is viable and effective for improving antiretroviral adherence . When the intervention is conducted by a peer the results are at least as good as those obtained by a health professional , and this implies cost-saving for the health system CONTEXT In order for patients to benefit from a multidisciplinary treatment approach , diverse providers must communicate on patient care . OBJECTIVE We sought to examine the effect of information exchange across multidisciplinary human immunodeficiency virus ( HIV ) care providers on patient health outcomes . DESIGN R and omized controlled trial , r and omized at the patient level . SETTING Six infectious disease clinics paired with 9 ancillary care setting s ( eg , HIV case management ) . PARTICIPANTS Two hundred fifty-four patients with HIV receiving care at the infectious disease clinics . INTERVENTION Health information was exchanged for 2 years per patient between medical and ancillary care providers using electronic health records and printouts inserted into charts . Medical care providers gave ancillary care providers HIV viral loads , CD4 values , current medications , and appointment attendance . Ancillary care providers gave medical providers the information on medication adherence and major changes ( eg , loss of housing ) . MAIN OUTCOME MEASURES We abstract ed from medical records HIV viral loads , CD4 counts , and antiretroviral medication prescriptions before and during the intervention . From 0- , 12- , and 24-month patient surveys , we assessed hospitalizations , emergency department use , and health-related quality of life measured by the Medical Outcomes Study Short Form-36 ( SF-36 ) . RESULTS No statistically significant differences between cases and controls were found across time for the following : proportion with suppressed viral load , changes in viral load or CD4 values , patients being prescribed antiretroviral medication , hospitalizations , emergency department visits , or any scale of the SF-36 . Trends were mixed but leaned toward better health for control participants . CONCLUSIONS The exchange of this specific set of information between HIV medical and ancillary care providers was neutral on a variety of patient health outcomes Objective Our objective was to examine the effects of exercise training ( EXS ) on quality of life ( QoL ) in highly active antiretroviral therapy (HAART)-treated HIV-positive ( HIV+ ) subjects with body fat redistribution ( BFR ) in Rw and a. Methods The effects of a r and omised controlled trial of EXS on QoL were measured using World Health Organisation Quality of Life (WHOQOL)-BREF in HIV+ subjects with BFR r and omised to EXS ( n = 50 ; BFR + EXS ) or no exercise training ( n = 50 ; BFR + noEXS ) . Results At 6 months , scores on the psychological [ 1.3 ( 0.3 ) vs. 0.5 ( 0.1 ) ; P < 0.0001 ] , independence [ 0.6 ( 0.1 ) vs. 0.0 ( 0.0 ) ; P < 0.0001 ] , social relationships [ 0.6 ( 0.2 ) vs. 0.0 ( 0.0 ) ; P < 0.0001 ] and HIV HAART-specific QoL domains [ 1.4 ( 0.2 ) vs. −0.1 ( 0.2 ) ; P < 0.0001 ] improved more in BFR + EXS than BFR + noEXS group , respectively . Self-esteem [ 1.3 ( 0.8 ) vs. 0.1 ( 0.6 ) ; P < 0.001 ] , body image [ 1.5 ( 0.6 ) vs. 0.0 ( 0.5 ) ; P < 0.001 ] and emotional stress [ 1.6 ( 0.7 ) vs. 0.2 ( 0.5 ) ; P < 0.001 ] improved more in the BFR + EXS group than BFR + noEXS group , respectively . Psychological [ 1.5 ( 0.2 ) vs. 1.1 ( 0.3 ) ; P < 0.0001 ] , social relationship [ 0.8 ( 0.2 ) vs. 0.4 ( 0.2 ) ; P < 0.0001 ] , and HIV HAART-specific well-being [ 1.8 ( 0.2 ) vs. 1.0 ( 0.0 ) ; P < 0.0001 ] improved more in BFR + EXS female than male subjects . Conclusions Exercise training improved several components of QoL in HAART-treated HIV+ African subjects with BFR . Exercise training is an inexpensive and efficacious strategy for improving QoL in HIV+ African subjects , which may improve HAART adherence and treatment initiatives in re source -limited areas of sub-Saharan Africa OBJECTIVES We examined findings from a r and omized controlled intervention trial design ed to improve the quality of life of people living with HIV in Thail and . METHODS A total of 507 people living with HIV were recruited from 4 district hospitals in northern and northeastern Thail and and were r and omized to an intervention group ( n = 260 ) or a st and ard care group ( n = 247 ) . Computer-assisted personal interviews were administered at baseline and at 6 and 12 months . RESULTS At baseline , the characteristics of participants in the intervention and st and ard care conditions were comparable . The mixed-effects models used to assess the impact of the intervention revealed significant improvements in general health ( B = 2.51 ; P = .001 ) and mental health ( B = 1.57 ; P = .02 ) among participants in the intervention condition over 12 months and declines among those in the st and ard care condition . CONCLUSIONS Our results demonstrate that a behavioral intervention was successful in improving the quality of life of people living with HIV . Such interventions must be performed in a systematic , collaborative manner to ensure their cultural relevance , sustainability , and overall success We examined the efficacy of a psycho-spiritual intervention of mantram repetition -- a word or phrase with spiritual associations repeated silently throughout the day -- on psychological distress ( intrusive thoughts , stress , anxiety , anger , depression ) , quality of life enjoyment and satisfaction , and existential spiritual well-being in HIV-infected adults . Using a 2-group by 4-time repeated measures design , 93 participants were r and omly assigned to mantram ( n = 46 ) or attention control group ( n = 47 ) . Over time , the mantram group improved significantly more than the control group in reducing trait-anger and increasing spiritual faith and spiritual connectedness . Actual mantram practice measured by wrist counters was inversely associated with non-HIV related intrusive thoughts and positively associated with quality of life , total existential spiritual well-being , meaning/peace , and spiritual faith . Intent-to-treat findings suggest that a mantram group intervention and actual mantram practice each make unique contributions for managing psychological distress and enhancing existential spiritual well-being in adults living with HIV/AIDS QUESTION What is the effect of a six-month , supervised , aerobic and resistance exercise program on self-efficacy in men living with human immunodeficiency virus ( HIV ) ? DESIGN R and omised , controlled trial . PARTICIPANTS 40 ( 5 dropouts ) men living with HIV , aged 18 years or older . INTERVENTION The experimental group participated in a twice-weekly supervised aerobic and resistance exercise program for six months and the control group participated in a twice-weekly unsupervised walking program and attended a monthly group forum . OUTCOME MEASURES The primary outcome measure was self-efficacy using the General Self-Efficacy Scale . Secondary outcome measures were cardiovascular fitness using the Kasch Pulse Recovery test , and health-related quality of life using the Medical Outcomes Study HIV Health Survey . Measures were taken by an assessor blinded to group allocation . RESULTS By six months , the experimental group had improved their self-efficacy by 6.8 points ( 95 % CI 3.9 to 9.7 , p < 0.001 ) and improved their cardiovascular fitness by reducing their heart rate by 20.2 bpm ( 95 % CI -25.8 to -14.6 , p < 0.001 ) more than the control group . Health-related quality of life improved in only two out of the eleven dimensions : the experimental group improved their overall health by 20.8 points ( 95 % CI 2.0 to 39.7 , p = 0.03 ) and their cognitive function by 14 points ( 95 % CI 0.7 to 27.3 , p = 0.04 ) more than the control group . CONCLUSION The findings of this study add to the known benefits of exercise for the HIV-infected population Stress is implicated in the pathogenesis and progression of HIV . The Transcendental Meditation ( TM ) is a behavioral stress reduction program that incorporates mind – body approach , and has demonstrated effectiveness in improving outcomes via stress reduction . We evaluated the feasibility of implementing TM and its effects on outcomes in persons with HIV . In this community-based single blinded Phase-I , r and omized controlled trial , outcomes ( psychological and physiological stress , immune activation , generic and HIV-specific health-related quality of life , depression and quality of well-being ) were assessed at baseline and at six months , and were compared using parametric and nonparametric tests . Twenty-two persons with HIV were equally r and omized to TM intervention or healthy eating ( HE ) education control group . Retention was 100 % in TM group and 91 % in HE control group . The TM group exhibited significant improvement in vitality . Significant between group differences were observed for generic and HIV-specific health-related quality of life . Small sample size may possibly limit the ability to observe significant differences in some outcomes . TM stress reduction intervention in community dwelling adults with HIV is viable and can enhance health-related quality of life . Further research with large sample and longer follow-up is needed to vali date our results Background Among people living with HIV ( PLHIV ) on antiretroviral therapy ( ART ) , it is important to determine how quality of life ( QOL ) may be improved and HIV-related stigma can be lessened over time . This study assessed the effect of peer support on QOL and internal stigma during the first year after initiating ART among a cohort of PLHIV in north-eastern Vietnam . Methods A sub- sample study of a r and omised controlled trial was implemented between October 2008 and November 2010 in Quang Ninh , Vietnam . In the intervention group , participants ( n = 119 ) received adherence support from trained peer supporters who visited participants ’ houses biweekly during the first two months , thereafter weekly . In the control group , participants ( n = 109 ) were treated according to st and ard guidelines , including adherence counselling , monthly health check and drug refills . Basic demographics were measured at baseline . QOL and internal stigma were measured using a Vietnamese version of the WHOQOL-HIVBREF and Internal AIDS-related Stigma Scale instruments at baseline and 12 months . T-tests were used to detect the differences between mean values , multilevel linear regressions to determine factors influencing QOL . Results Overall , QOL improved significantly in the intervention group compared to the control group . Among participants initiating ART at clinical stages 3 and 4 , education at high school level or above and having experiences of a family member dying from HIV were also associated with higher reported QOL . Among participants at clinical stage 1 and 2 , there was no significant effect of peer support , whereas having children was associated with an increased QOL . Viral hepatitis was associated with a decreased QOL in both groups . Lower perceived stigma correlated significantly but weakly with improved QOL , however , there was no significant relation to peer support . Conclusion The peer support intervention improved QOL after 12 months among ART patients presenting at clinical stages 3 and 4 at baseline , but it had no impact on QOL among ART patients enrolled at clinical stages 1 and 2 . The intervention did not have an effect on Internal AIDS-related stigma . To improve QOL for PLHIV on ART , measures to support adherence should be context ualized in accordance with individual clinical and social needs A pretest-posttest , repeated- measures design was used to evaluate the effects of two stress management interventions on a battery of outcomes derived from a psychoneuroimmunological ( PNI ) framework . The effects of cognitive-behavioral relaxation training groups ( CBSM ) and social support groups ( SSG ) were compared with a WAIT-listed control group on the outcomes of psychosocial functioning , quality of life , neuroendocrine mediation , and somatic health . Participants were 148 individuals ( 119 men , 29 women ) , diagnosed with HIV disease ; 112 ( 76 % ) completing the study groups . Using analysis of covariance , the CBSM group was found to have significantly higher postintervention emotional well-being and total quality -of-life scores than did either the SSG or WAIT groups . SSG participants had significantly lower social/family well-being scores immediately postintervention and lower social support scores after 6 months . The findings point to a pressing need for further , well-controlled research with these common intervention modalities CONTEXT Advances in antiretroviral therapy ( ART ) for HIV offer life-extending benefit ; however , the side effects associated with ART use negatively impact quality of life and medication adherence among people living with HIV . OBJECTIVES This study tested the efficacy of Mindfulness-Based Stress Reduction ( MBSR ) for reducing ART symptoms and bother/distress related to ART side effects . Secondary aims were to test the impact of MBSR on medication adherence and psychological functioning . METHODS Seventy-six people living with HIV who were actively taking ART and reported distress from ART-related side effects were r and omly assigned to an MBSR program or a wait-list control ( WLC ) st and ard care condition . We measured side effects , ART adherence , perceived stress , depression , positive and negative affect , and mindfulness at three time points : baseline , three-month follow-up , and six-month follow-up . Side effects and related distress were assessed separately from other symptoms . RESULTS Compared with a WLC , participants in the MBSR condition experienced a reduction in the frequency of symptoms attributable to ARTs at three months post-intervention ( mean difference=0.33 ; 95 % confidence interval [CI]=0.01 , 0.66 ; t(132)=2.04 , P=0.044 ) and six months post-intervention ( mean difference=0.38 ; 95 % CI=0.05 , 0.71 ; t(132)=2.27 , P=0.025 ) . MBSR participants also experienced a reduction in distress associated with those symptoms at three months post-intervention ( mean difference=0.47 ; 95 % CI=0.003 , 0.94 ; t(132)=1.99 , P=0.048 ) compared with the WLC condition . CONCLUSION MBSR is a promising approach for reducing HIV treatment-related side effects Patients ' knowledge of their HIV condition and its treatment , which has been recognized as a factor that influences adherence to antiretroviral therapy , can be improved through educational programs . This prospect i ve , r and omized , controlled trial compared an experimental group that participated in an educational program and a control group with st and ard care . The study evaluated the impact of an educational intervention on adherence to antiretroviral therapy , patients ' knowledge , quality of life , and therapeutic response in patients treated with highly active antiretroviral therapy . Three hundred twenty-six patients were analyzed at inclusion . A higher level of adherence was associated with patients who were older , had higher incomes , and did not smoke . CD4 cell count and plasma viral load were correlated with adherence at entry . The educational intervention had an impact on adherence and knowledge in the experimental group at 6 months , which was maintained at 12 and 18 months . A delayed increase in adherence was observed in the control group at 12 months . No significant impact on quality of life was observed over time . The patients ' health status improved in 56 % of the experimental group subjects and 50 % of the control subjects . However , no significant impact was shown on CD4 cell count and plasma viral load . This study shows that an educational intervention improves adherence to antiretroviral regimens and health status and suggests that it should be initiated early in therapy Patients on highly active antiretroviral therapy ( HAART ) spend less time on vigorous activities due to lower aerobic capacity with functional limitations that can be attributed to a detraining effect , result ing in a poor quality of life ( QoL ) . The overall aims of rehabilitation are to restore , to maintain , and to enhance the QoL and this detraining effect could possibly be reversed by a rehabilitation program . This r and omized controlled prospect i ve longitudinal descriptive study evaluated the impact of a rehabilitation program of moderate-intensity cycling and treadmill walking exercises with a home program on the QoL for individuals on HAART . Fifty-two participants with baseline QoL values formed the experimental and control groups with a 3-month pretest and posttest using the short-form health survey ( SF-36 ) question naire . No adverse effects from exercises were experienced , and 20 ( 77 % ) of the experimental and 16 ( 62 % ) of the controls completed the program . A significantly higher number of women dropped out ( P<0.04 ) , with four ( 15 % ) from the experimental group and six ( 23 % ) from the control group . There were significant improvements in all QoL domains ( P<0.05 ) for the experimental group compared with the control group , with the physical component summary ( P<0.018 ) and mental component summary ( P<0.021 ) scores being significantly higher after rehabilitation . Sick leave decreased from a mean of 7 days to 3 for the experimental group and 5 for the control group . These results indicate that a rehabilitation program of moderate-intensity exercises with a home program significantly improved the QoL for individuals on HAART . Further research with a comprehensive rehabilitation program and a larger sample is recommended This 6-month r and omized controlled trial evaluated the impact on quality of life ( QOL ) of a medication reminder device for patients with HIV . Patients were eligible if they had taken three or fewer highly active antiretroviral therapy ( HAART ) regimens or were treatment naïve . The intervention group received the Disease Management Assistance System ( DMAS ) , a prompting device that verbally reminds patients at medication times and electronically records doses , and a monthly 30 minute adherence educational session . Controls received education only . QOL was measured at baseline and 6 months using the Centers for Epidemiologic Studies Depression Scale ( CES-D ) , Instrumental Activities of Daily Living ( IADLs ) , and the Medical Outcomes Study HIV Health Survey ( MOS-HIV ) . At baseline , 62 patients completed surveys ( 31 control , 31 DMAS ) ; at month 6 , 48 patients completed surveys ( 23 control , 25 DMAS ) . At month 6 , controls had improved QOL scores for CES-D , IADLs , physical health , general health , pain , QOL , and role functioning , while participants in the DMAS arm had some deterioration in QOL scores . These differences persisted after controlling for demographics , baseline CD4 , and adherence . DMAS was associated with improved adherence but decreased QOL This intervention sought to improve overall quality of life and health behavior in women living with human immunodeficiency virus ( HIV ) . We contrasted the effect of a group cognitive behavioral stress management expressive supportive therapy ( CBSM+ ) intervention plus a healthier lifestyles ( HL ) component with an individual educational/informational format plus HL on HIV-medication adherence . Women , n = 237 , predominantly African-American and Latina , living with HIV were recruited from Miami , New York and New Jersey and r and omized to group or individual conditions ( ten weekly sessions ) plus group or individual HL , i.e. , four conditions . Women reported relatively high levels of adherence at baseline . Participants in any of the group conditions increased self-reported adherence and emotion-focused coping skills in comparison with individual participation . This study suggests that group interventions may be an important adjunct in increasing medication adherence for HIV positive women Background Human immunodeficiency virus ( HIV ) infection has become a serious health problem for low-income African American women in their childbearing years . Interventions that help them cope with feelings about having HIV and increase their underst and ing of HIV as a chronic disease in which self-care practice s , regular health visits , and medications can improve the quality of life can lead to better health outcomes . Objective This study aim ed to determine the efficacy of an HIV self-care symptom management intervention for emotional distress and perceptions of health among low-income African American mothers with HIV . Method Women caregivers of young children were r and omly assigned to self-care symptom management intervention or usual care . The intervention , based on a conceptual model related to HIV in African American women , involved six home visits by registered nurses . A baseline pretest and two posttests were conducted with the mothers in both groups . Emotional distress was assessed as depressive symptoms , affective state , stigma , and worry about HIV . Health , self-reported by the mothers , included the number of infections and aspects of health-related quality of life ( i.e. , perception of health , physical function , energy , health distress , and role function ) . Results Regarding emotional distress , the mothers in the experimental group reported fewer feelings of stigma than the mothers in the control group . Outcome assessment s of health indicated that the mothers in the experimental group reported higher physical function scores than the control mothers . Within group analysis over time showed a reduction in negative affective state ( depression/dejection and tension/anxiety ) and stigma as well as infections in the intervention group mothers , whereas a decline in physical and role function was found in the control group . Conclusions The HIV symptom management intervention has potential as a case management or clinical intervention model for use by public health nurses visiting the home or by advanced practice nurses who see HIV-infected women in primary care or specialty clinics Objective : To determine the effects of cognitive – behavioral stress management ( CBSM ) training on clinical and psychosocial markers in HIV-infected persons . Methods : A r and omized controlled trial in four HIV outpatient clinics of 104 HIV-infected persons taking combination antiretroviral therapy ( cART ) , measuring HIV-1 surrogate markers , adherence to therapy and well-being 12 months after 12 group sessions of 2 h CBSM training . Results : Intent-to-treat analyses showed no effects on HIV-1 surrogate markers in the CBSM group compared with the control group : HIV-1 RNA < 50 copies/ml in 81.1 % [ 95 % confidence interval ( CI ) , 68.0–90.6 ] and 74.5 % ( 95 % CI , 60.4–85.7 ) , respectively ( P = 0.34 ) , and mean CD4 cell change from baseline of 53.0 cells/μl ( 95 % CI , 4.1–101.8 ) and 15.5 cells/μl ( 95 % CI , −34.3 to 65.4 ) , respectively ( P = 0.29 ) . Self-reported adherence to therapy did not differ between groups at baseline ( P = 0.53 ) or at 12 month 's post-intervention ( P = 0.47 ) . Significant benefits of CBSM over no intervention were observed in mean change of quality of life scores : physical health 2.9 ( 95 % CI , 0.7–5.1 ) and −0.2 ( 95 % CI , −2.1 to 1.8 ) , respectively ( P = 0.05 ) ; mental health 4.8 ( 95 % CI , 1.8–7.3 ) and −0.5 ( 95 % CI , −3.3 to 2.2 ) ( P = 0.02 ) ; anxiety −2.1 ( 95 % CI , −3.6 to −1.0 ) and 0.3 ( 95 % CI , −0.7 to 1.4 ) , respectively ( P = 0.002 ) ; and depression −2.1 ( 95 % CI , −3.2 to −0.9 ) and 0.02 ( 95 % CI , −1.0 to 1.1 ) , respectively ( P = 0.001 ) . Alleviation of depression and anxiety symptoms were most pronounced among participants with high psychological distress at baseline . Conclusion : CBSM training of HIV-infected persons taking on cART does not improve clinical outcome but has lasting effects on quality of life and psychological well-being Forty-six Chinese patients with symptomatic human immunodeficiency virus ( HIV ) participated in a comparative study assessing the effectiveness of cognitive-behavioral group therapy ( CBT ) and peer support/counseling group therapy ( PSC ) in relation to improving mood and quality of life and decreasing uncertainty in illness as compared to a group receiving routine treatment with no formal psychosocial intervention . The CBT group consisted of 10 subjects , the PSC group of 10 subjects , and the comparison group of 26 subjects . There was a 24 % attrition rate . The intervention groups received 12 weekly sessions of therapy over 3 months . Assessment of mood states was carried out before r and omization ( baseline data ) , immediately postintervention ( 3-month time point ) and followed-up 3 months later ( 6-month time point ) . Assessment of quality of life and uncertainty in illness was carried out before r and omization and at the 6-month follow-up time point . Results indicated that the mood of the participants in the CBT group improved in terms of anger , tension-anxiety , depression , confusion , and overall mood . The quality of life in this group was significantly improved compared to the other two groups , as was uncertainty in illness . In the PSC group a worsening of psychologic functioning was observed immediately postintervention , but this picture dramatically improved at the follow-up assessment with improvements of up to 34 % . Quality of life also improved over time in this group by almost 5 % , but results did not reach statistical significance . This study demonstrated that psychologic interventions could decrease psychologic distress and improve quality of life in symptomatic HIV patients , indicating their use should be incorporated in the management of care of people living with HIV/AIDS 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 Abstract Objective . To test the impact of participation in a peer-based intervention for symptom management for women living with HIV infection on selected outcome measures including , symptom intensity , medication adherence , viral control , and quality of life . Design . R and omized clinical trial . Methods . Participants were recruited using a convenient , consecutive sampling method . Those participants r and omized to the experimental condition attended seven , peer-led sessions over seven weeks . Participants r and omized to the control condition received a copy of HIV Symptom Management Strategies : A Manual for People Living with HIV/AIDS . Participants completed four surveys assessing change over time in the aforementioned outcome variables . Results . Eighty-nine HIV-infected women followed over 14 weeks and there were no differences between the two groups on baseline demographic variables . Mixed-effects regression indicated no significant difference between groups across time in total symptom intensity score and medication adherence . There was a significant difference between groups across time for two of the nine quality of life scales – HIV Mastery ( χ 2=25.08 ; p<0.005 ) and Disclosure Worries ( χ 2=24.67 ; p<0.005 ) . Conclusions . In urban-dwelling women living with HIV/AIDS , results suggest that a peer-based symptom management intervention may not decrease symptom intensity or increase medication adherence . There is positive evidence that suggests that the intervention may increase some important aspects of quality of life . However , further research is warranted to eluci date the effect of peer-based interventions in achieving positive self-management outcomes Abstract Depressive symptoms are highly prevalent , underdiagnosed , and undertreated in people living with HIV/AIDS ( PLWH ) , and are associated with poorer health outcomes . This r and omized controlled trial examined the effects of the HIV/AIDS Symptom Management Manual self-care symptom management strategies compared with a nutrition manual on depressive symptoms in an international sample of PLWH . The sample consisted of a sub-group ( N=222 ) of participants in a larger study symptom management study who reported depressive symptoms . Depressive symptoms of the intervention ( n=124 ) and control ( n=98 ) groups were compared over three months : baseline , one-month , and two-months . Use and effectiveness of specific strategies were examined . Depressive symptom frequency at baseline varied significantly by country ( χ 2 12.9 ; p=0.04 ) . Within the intervention group there were significant differences across time in depressive symptom frequency [ F(2 , 207 ) = 3.27 , p=0.05 ] , intensity [ F(2 , 91 ) = 4.6 , p=0.01 ] , and impact [ F(2 , 252 ) = 2.92 , p= 0.05 ) , and these were significantly lower at one month but not at two months , suggesting that self-care strategies are effective in reducing depressive symptoms , however effects may be short term . Most used and most effective self-care strategies were distraction techniques and prayer . This study suggests that people living with HIV can be taught and will employ self-care strategies for management of depressive symptoms and that these strategies are effective in reducing these symptoms . Self-care strategies are noninvasive , have no side-effects , and can be readily taught as an adjunct to other forms of treatment . Studies are needed to identify the most effective self-care strategies and quantify optimum dose and frequency of use as a basis for evidence -based practice OBJECTIVE People living with HIV infection are at increased risk for developing cardiovascular disease ( CVD ) . Safe and effective interventions for lowering CVD risk in HIV infection are high priorities . We conducted a prospect i ve , r and omized , controlled study to evaluate whether a yoga lifestyle intervention improves CVD risk factors , virological or immunological status , or quality of life ( QOL ) in HIV-infected adults relative to st and ard of care treatment in a matched control group . METHODS Sixty HIV-infected adults with mild-moderate CVD risk were assigned to 20 weeks of supervised yoga practice or st and ard of care treatment . Baseline and week 20 measures were : 2-h oral glucose tolerance test with insulin monitoring , body composition , fasting serum lipid/lipoprotein profile , resting blood pressures , CD4 T-cell count and plasma HIV RNA , and the Medical Outcomes Study Short Form (SF)-36 health-related QOL inventory . RESULTS Resting systolic and diastolic blood pressures improved more ( P=0.04 ) in the yoga group ( -5 + /- 2 and -3 + /- 1 mmHg , respectively ) than in the st and ard of care group ( + 1 + /- 2 and + 2 + /- 2 mmHg , respectively ) . However , there was no greater reduction in body weight , fat mass or proatherogenic lipids , or improvements in glucose tolerance or overall QOL after yoga . Immune and virological status was not adversely affected . CONCLUSION Among traditional lifestyle modifications , yoga is a low-cost , simple to administer , nonpharmacological , popular behavioural intervention that can lower blood pressure in pre-hypertensive HIV-infected adults with mild-moderate CVD risk factors |
12,128 | 18,186,076 | In the overall meta- analysis we found no evidence of association between genetic variation at the 5-HTTLPR locus and OCD .
In the stratified meta-analyses , we demonstrated a significant association between the l-allele and OCD in family-based association studies and in studies involving children and Caucasians .
Our meta- analysis suggests the possibility that the l-allele may be associated with OCD in specific OCD subgroups such as childhood-onset OCD and in Caucasians .
Further meta-analyses based on individual patient data would be helpful in determining whether age of OCD onset , gender and the presence of comorbid illness ( e.g. , tics ) moderates the relationship between 5-HTTLPR and OCD | null | null |
12,129 | 22,336,869 | Relief of headache-associated symptoms , including nausea , photophobia , and phonophobia , was greater with sumatriptan than with placebo , and use of rescue medication was lower with sumatriptan than placebo .
For the most part , adverse events were transient and mild and were more common with sumatriptan than placebo .
Subcutaneous sumatriptan is effective as an abortive treatment for acute migraine attacks , quickly relieving pain , nausea , photophobia , phonophobia , and functional disability , but is associated with increased adverse events | BACKGROUND Migraine is a highly disabling condition for the individual and also has wide-reaching implication s for society , healthcare services , and the economy .
Sumatriptan is an abortive medication for migraine attacks , belonging to the triptan family .
Subcutaneous administration may be preferable to oral for individuals experiencing nausea and /or vomiting OBJECTIVES To determine the efficacy and tolerability of subcutaneous sumatriptan compared to placebo and other active interventions in the treatment of acute migraine attacks in adults . | Summary Two double-blind , r and omized , placebo-controlled multicentre studies were carried out to assess the efficacy and tolerability of subcutaneous ( s. c. ) injections of 1 - 3 mg and 1 - 8 mg sumatriptan , respectively , in the acute treatment of migraine . Data are presented from a total of 519 patients . In both studies , the primary endpoint of efficacy was a reduction in headache severity from severe or moderate to mild or no headache . All doses of sumatriptan were significantly more effective than placebo in relieving symptoms , and the response appeared to be dose-related ; an effective response to treatment was achieved within 30 min in 73 % of patients treated with 6 mg sumatriptan and 80 % of patients treated with 8 mg sumatriptan s. c. , compared with 22 % for placebo . Sumatriptan was well tolerated and the majority of adverse events were mild and transient . The most frequent complaint was irritation and pain at the site of injection . No changes in laboratory values were noted and ECG readings were unaltered by treatment . On the basis of these results , the 6 mg subcutaneous dose has been selected for further evaluation in large-scale studies BACKGROUND Sumatriptan is effective for the treatment of acute migraine . However , headache may recur in about 30 % of patients within 24 hours of successful treatment . OBJECTIVE To evaluate the efficacy of oral sumatriptan , 100 mg , in the treatment of headache recurring within 24 hours of achieving headache resolution with subcutaneous sumatriptan , 6 mg . STUDY DESIGN Subcutaneous sumatriptan was administered for up to 12 migraine attacks in a r and omized , double-blind , parallel-group study . Patients whose headache was completely resolved 90 minutes after subcutaneous dosing received either oral sumatriptan or placebo at the onset of recurrent headache . Patients whose headache was not completely resolved were offered rescue medication , including sumatriptan . Patients rated headache severity for 24 hours . SETTING Fifteen US outpatient clinics . MAIN OUTCOME MEASURE Percentage of patients with relief of recurrent headache and adverse events . RESULTS Approximately 90 % of patients achieved relief of headache ( severe or moderate headache reduced to mild or no headache ) by 90 minutes after unblinded subcutaneous administration of sumatriptan . Efficacy rates were at least 80 % regardless of whether the headache fulfilled the International Headache Society criteria for migraine . About 64 % of patients achieved complete relief . Oral sumatriptan , 100 mg , relieved moderate or severe recurrent headache within 4 hours in up to 81 % of patients . Oral sumatriptan administered as rescue medication to patients not headache-free did not relieve persistent headache . The incidence , pattern , and severity of adverse events after combined subcutaneous and oral administration of sumatriptan were similar to those after subcutaneous administration alone . CONCLUSIONS Oral sumatriptan was consistently effective in the treatment of headache recurrence 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 Objective : To evaluate the efficacy and safety of sumatriptan , a 5-HTa receptor agonist , in patients with menstruationassociated migraine . Methods : Two double-blind , placebo-controlled , singleattack parallel group studies of subcutaneous sumatriptan were conducted for the acute treatment of migraine . A retrospective analysis of 1104 patients produced 157 women who were treated for a menstruation-associated migraine ( defined as a migraine beginning between 1 day before and 4 days after the onset of menstrual flow ) and 512 women treated for nonmenstrual migraine . We excluded 435 other patients who were either male ( 123 ) , women with hysterectomies ( 260 ) , or women with missing data ( 52 ) . Patients with moderate or severe pain were treated with 6 mg subcutaneous sumatriptan or placebo . One hour after treatment , response rates of headache severity and associated symptoms were measured . Menstruation-associated migraine patients were compared to female patients with nonmenstrual migraine . Migraine recurrence was analyzed retrospectively for 24 hours . Results : At 1 hour , 80 % of the sumatriptan-treated menstrual-migraine patients had pain relief ( reduction of severe or moderate pain to mild or no pain ) , compared to 19 % of the placebo patients ( P < .001 ) . Sumatriptan also treated nausea and photophobia more effectively in menstrual-migraine patients than did placebo . Response rates for pain and associated symptoms were similar between patients with menstruation-associated and nonmenstrual migraines . Adverse effects were also similar between the groups . Conclusion : Sumatriptan was as effective and well tolerated for menstruation-associated migraine as it was for nonmenstrual migraine The results of the very first large-scale placebo-controlled dose-response trial with the novel selective 5-hydroxytryptamine1-like ( 5HT 1-like ) receptor agonist sumatriptan are presented . We studied the efficacy and tolerability of subcutaneous injections of 1 mg , 2 mg and 3 mg of sumatriptan in alleviating migraine attacks in a double-blind , placebo-controlled , parallel-group , multicentre clinical trial . Six-hundred and ninety patients were r and omized and 685 received study medication . At 30 min , reduction of headache severity to mild or none ( primary efficacy endpoint ) was achieved in 22 % ( 95 % CI : 15 - 28 % ) of placebo-treated patients and in 39 % ( CI : 31 - 46 % ) of patients treated with 1 mg sumatriptan , 44 % ( CI : 36 - 51 % ) treated with 2 mg sumatriptan and 55 % ( CI : 48 - 63 % ) treated with 3 mg sumatriptan . Differences from placebo were 17 % ( CI : 8 - 27 % ) for 1 mg sumatriptan , 22 % ( CI : 13 - 32 % ) for 2 mg sumatriptan and 34 % ( CI : 24 - 44 % ) for 3 mg sumatriptan ( p < 0.001 for all three comparisons ) . Other migraine symptoms were also more effectively treated by sumatriptan than by placebo . Subsequently , an open-label 3 mg dose subcutaneous sumatriptan was given to partial or non-responders . Thirty minutes after this open dose the response rate to sumatriptan had improved to between 70 and 80 % . Adverse events after sumatriptan were minor and short-lived . We conclude that subcutaneous sumatriptan is well tolerated in doses up to 3 + 3 mg and may rapidly abort migraine attacks This double-blind , placebo-controlled , multicenter , crossover study investigated the efficacy and tolerability of sumatriptan administered for up to three separate migraine attacks . One hundred twenty adults received sumatriptan ( SC , 6 mg ; three attacks ) and placebo ( one attack ) . Patients completed question naires assessing the impact of migraine on their lives and the performance of sumatriptan relative to their usual acute therapies . Sumatriptan statistically outperformed placebo on all efficacy measures , including pain severity ; presence/absence of nausea , vomiting , phonophobia , and photophobia ; rescue medication use ; and clinical disability . Efficacy was consistently maintained with repeated administration . For all attacks , pain relief 90 minutes postdose occurred in 86 % to 90 % of sumatriptan-treated patients , compared with 9 % to 38 % of placebo-treated patients . Sumatriptan was well tolerated , and the frequency and severity of adverse events did not change with repeated administration . Patients ' perceptions of sumatriptan were consistent with clinical data demonstrating the drug 's high degree of efficacy and tolerability OBJECTIVE To evaluate the impact of sumatriptan succinate injection compared with placebo on productivity loss during a migraine attack in the workplace . DESIGN R and omized , double-blind , placebo-controlled , parallel-group clinical trial . SETTING Fifteen clinical centers in the United States . PATIENTS One hundred thirty-five patients 18 years and older diagnosed as having migraine according to International Headache Society criteria . INTERVENTIONS Patients self-administered sumatriptan injection ( 6 mg ) or matching placebo to treat a moderate or severe migraine occurring within the first 4 hours of a minimum 8-hour work shift . MAIN OUTCOME MEASURES Mean productivity loss 2 hours after dosing and across the work shift ; percentages of patients returning to normal work performance within 2 hours after dosing and across the work shift ; percentages of patients experiencing headache relief ( reduction of moderate or severe predose pain to mild or no pain ) 1 and 2 hours after dosing . RESULTS Mean productivity loss was significantly ( P < or = .002 ) lower in the sumatriptan group compared with the placebo group both during the 2-hour postdose period ( sumatriptan , 39 minutes ; placebo , 54 minutes ) and across the work shift ( sumatriptan , 86 minutes ; placebo , 168 minutes ) . Significantly ( P<.001 ) greater percentages of patients in the sumatriptan group compared with the placebo group returned to normal work performance by 2 hours after dosing ( sumatriptan , 52 % ; placebo , 9 % ) and across the work shift ( sumatriptan , 66 % ; placebo , 18 % ) . Significantly ( P < or = .001 ) greater percentages of patients in the sumatriptan group compared with the placebo group experienced headache relief 1 hour after dosing ( sumatriptan , 69 % ; placebo , 18 % ) and 2 hours after dosing ( sumatriptan , 79 % ; placebo , 32 % ) . CONCLUSION Sumatriptan reduced migraine-associated productivity loss during a minimum 8-hour work shift by approximately 50 % compared with placebo and alleviated headache in more than three fourths of patients We compared the efficacy and safety of subcutaneous ( SC ) sumatriptan ( 6 mg ) with that of dihydroergotamine ( DHE ) nasal spray ( 1 mg plus optional 1 mg ) in the acute treatment of migraine . Two hundred sixty-six adult migraineurs ( International Headache Society criteria ) completed a multicenter , double-blind , double-dummy , cross-over study . Patients took SC sumatriptan for one attack and DHE nasal spray for the other in r and om order . Data from both treatment periods show that at all time points from 15 minutes , SC sumatriptan was significantly better than DHE nasal spray at providing both headache relief ( moderate/severe headache improving to mild/none ) and resolution of headache . Similarly , SC sumatriptan was superior to DHE nasal spray for the other efficacy end points assessed in the study . Patients reported that both treatments were well tolerated . Adverse events were reported by 43 % of patients taking SC sumatriptan and 22 % of patients taking DHE nasal spray . These were usually mild and transient . We conclude that subcutaneous sumatriptan has a faster onset of action than DHE nasal spray and provides greater relief of acute migraine symptoms . NEUROLOGY 1996;47 : 361 - OBJECTIVES : To investigate the efficacy of a second subcutaneous dose of 6 mg sumatriptan in the treatment of recurrence of headache after successful treatment of a migraine attack with an initial 6 mg dose . METHODS : In a prospect i ve , r and omised , placebo controlled , double blind , parallel group study , 803 patients were treated for one to three migraine attacks with severe or moderate headache with a subcutaneous injection of 6 mg sumatriptan . Any subsequent recurrence of migraine headache was treated with a r and omised second injection of sumatriptan or placebo . Recurrence was defined as a headache of moderate or severe intensity occurring 1 - 24 hours after the initial dose in a patient whose headache had been relieved by sumatriptan ( reduction of headache severity from severe or moderate to mild or none after one hour ) . RESULTS : Headache recurrence was reported by 10%-15 % of patients . At each attack , 6 mg sumatriptan given subcutaneously was significantly ( P < 0.0005 ) more effective than placebo at relieving recurrent headache after one hour ( 84%-93 % v 31%-50 % of patients ) ; 76%-83 % of patients reported headache relief one hour after the initial dose of sumatriptan . Sumatriptan was generally well tolerated . CONCLUSIONS : Up to 15 % of patients with migraine experience significant recurrence of headache after successful treatment with subcutaneous sumatriptan , and this recurrence is effectively treated by a further dose of subcutaneous sumatriptan OBJECTIVES To investigate whether acupuncture is superior to placebo and equivalent to sumatriptan for the early treatment of an acute migraine attack . DESIGN R and omized , partly double-blind ( sumatriptan versus placebo ) trial . SETTING Two hospitals in Germany ( one specialized in traditional Chinese medicine and one in the treatment of headache ) . SUBJECTS A total of 179 migraineurs experiencing the first symptoms of a developing migraine attack . INTERVENTIONS Traditional Chinese acupuncture , sumatriptan ( 6 mg subcutaneously ) or placebo injection . MAIN OUTCOME MEASURE Number of patients in whom a full migraine attack ( defined as severe migraine headache ) within 48 h was prevented . In patients who developed a migraine attack in spite of early treatment , acupuncture and sumatriptan were applied a second time , whilst patients initially r and omized to placebo received sumatriptan . RESULTS A full migraine attack was prevented in 21 of 60 ( 35 % ) patients receiving acupuncture , 21 of 58 ( 36 % ) patients receiving sumatriptan and 11 of 61 ( 18 % ) patients receiving placebo ( relative risk of having a full attack 0.79 ( 95 % CI , 0.64 - 0.99 ) for acupuncture versus placebo , and 0.78 ( 95 % CI , 0.62 - 0.98 ) for sumatriptan versus placebo ) . Response to the second intervention in patients who developed a full attack was better with sumatriptan ( 17/31 patients who received sumatriptan twice and 37/46 patients who had had placebo first ) than with acupuncture ( 4/31 ) . The number of patients reporting side-effects was 14 in the acupuncture group , 23 in the sumatriptan group and 10 in the placebo group . CONCLUSIONS In this trial acupuncture and sumatriptan were more effective than a placebo injection in the early treatment of an acute migraine attack . When an attack could not be prevented , sumatriptan was more effective than acupuncture at relieving headache Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included . The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo and the alternative medication for the second attack ( cross-over ) . When sumatriptan was compared to placebo , significantly more of the 209 evaluable patients reported headache relief at one hour ( 56 % v 8 % , p < 0.001 ) and two hours ( 62 % v 15 % , p < 0.001 ) after the first injection . Resolution of nausea , photophobia and phonophobia was significantly more common in patients on sumatriptan than on placebo ( p < 0.001 for all comparisons ) . The adverse events were usually transient and of mild or moderate severity , although , three patients withdrew due to adverse events . Ninety-five percent of patients evaluated by a neurological research fellow met the International Headache Society 's criteria for migraine . In general practice , sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine SYNOPSIS Objective . To evaluate the therapeutic response to sumatriptan in the acute migraine attack . Material and methods . Two hundred and thirty migraineurs diagnosed by their general practitioners in accordance with their usual practice were included in the study . The patients treated two migraine attacks at home by subcutaneous injection of sumatriptan or placebo for the first attack and the alternative medication , i.e. placebo or sumatriptan , for the second attack ( crossover ) . Following treatment , a neurology resident interviewed and examined the patients , Results . When sumatriptan was compared to placebo , significantly more of the 209 evaluable patients reported headache relief at I h ( 56 % vs 8 % , p < 0.001 ) and 2 h ( 62 % vs 15 % , p < 0.001 ) after the first injection . Resolution of nausea , photophobia , and phonophobia was significantly more common in patients on sumatriptan than in those on placebo ( p < 0.001 for all comparisons ) . The adverse events were usually transient and of mild or moderate severity ; however , three patients withdrew due to adverse events . Ninety-five percent of patients evaluated by a neurology resident met the IHS criteria for migraine . Conclusion . In general practice , sumatriptan taken subcutaneously using an autoinjector at home was an effective and well tolerated acute treatment for migraine OBJECTIVE To evaluate the efficacy and tolerability of sumatriptan , 50-mg and 100-mg tablets , compared with placebo for treatment of migraine at the first sign of pain . PATIENTS AND METHODS Two identical multicenter r and omized , double-blind , placebo-controlled , single-attack studies were conducted from May through November 2000 in adults ( aged 18 - 65 years ) . Patients treated migraine at the first sign of pain , while pain was mild , but not more than 2 hours after onset with oral sumatriptan , 50 mg or 100 mg , or matching placebo . The primary end point was pain-free relief at 2 hours after treatment with 50 mg of sumatriptan compared with placebo . RESULTS There were 354 patients in study 1 and 337 patients in study 2 . Significantly more patients treated with sumatriptan , 50 mg and 100 mg , were completely free from pain 2 and 4 hours after treatment vs patients treated with placebo ( at 2 hours , 50 % and 57 % vs 29 % ; at 4 hours , 61 % and 68 % vs 30 % ; for both , P < .001 ) . Also , significantly more patients treated with sumatriptan , 50 mg and 100 mg , were migraine-free ( no pain or associated symptoms ) vs those treated with placebo at 2 and 4 hours after treatment ( at 2 hours , 43 % and 49 % vs 24 % ; at 4 hours , 54 % and 63 % vs 28 % ; for both , P < .001 ) . The incidence of overall adverse events was low with the 50- and 100-mg dose of sumatriptan ( placebo , 7 % ; sumatriptan at 50 mg , 14 % ; sumatriptan at 100 mg , 16 % ) . CONCLUSIONS Treatment of migraine at the first sign of pain with sumatriptan , 50-mg and 100-mg tablets , provides superior pain-free relief at 2 and 4 hours after treatment compared with placebo . Results of these studies suggest that sumatriptan at 100 mg may be more efficacious than at 50 mg when used in the early treatment paradigm . Because these studies were not powered to detect statistical differences between active doses , studies to investigate this finding are warranted OBJECTIVE The aim of this study was to assess the efficacy and tolerability of sumatriptan injection in the treatment of morning migraine . METHODS In 2 multicenter ( 20 sites for study 1 and 25 sites for study 2 ) , r and omized , double-blind , controlled , parallel-group studies , male and female patients aged 18 to 65 years with migraine meeting International Headache Society criteria received SC sumatriptan succinate injection 6 mg or inactive vehicle ( control ) for the outpatient treatment of a single morning migraine , defined as migraine with moderate or severe pain on awakening . The primary end point was the percentage of patients who achieved pain-free relief ( moderate or severe pain reduced to no pain ) at 2 hours after treatment . Tolerability was assessed using spontaneous reporting or noted by a clinician during the studies , assessed at the return visit . RESULTS The efficacy analysis included , in the succinate group , 145 patients in study 1 , 148 in study 2 ; control , 152 in study 1 , 139 in study 2 . The mean ( SD ) ages in the sumatriptan group were 40.2 ( 9.7 ) and 38.8 ( 10.1 ) years in studies 1 and 2 , respectively ; control , 41.4 ( 10.4 ) and 39.3 ( 9.7 ) years . The majority of patients in the 2 studies were female ( sumatriptan , 84 % and 93 % in studies 1 and 2 , respectively ; control , 82 % and 81 % ) and white ( sumatriptan , 83 % and 81 % ; control , 78 % and 89 % ) . Two hours after treatment , 48 % and 57 % of patients treated with sumatriptan injection compared with 18 % and 19 % of control patients reported pain-free relief in studies 1 and 2 , respectively ( both , P < 0.001 ) . Two hours after treatment , 72 % and 77 % of patients treated with sumatriptan injection reported headache relief ( moderate or severe pain reduced to mild or no pain ) compared with 32 % and 41 % of control patients ( both , P < 0.001 ) . Onset of efficacy versus control ( the first time point with statistical significance of pain relief ) was observed beginning 10 minutes postdose ( P < 0.05 sumatriptan injection vs placebo across pooled studies ) . Mean time to efficacy in the sumatriptan group was 10 minutes ( P < 0.05 vs controls ) . The most commonly reported adverse events were nausea ( sumatriptan , 6 % and 4 % ; control , 2 % and 2 % ) and injection-site reaction ( ie , burning or stinging at the injection site ) ( sumatriptan , 5 % and 5 % ; control , 2 % and 1 % ) . Injection-site reaction was also the only adverse event considered treatment related and reported in > or = 5 % of all patients . CONCLUSION The results of these 2 r and omized , double-blind , controlled studies suggest that sumatriptan injection was effective and well tolerated in the acute treatment of morning migraine in these adults SYNOPSIS INTRODUCTION AND MATERIAL In the Hospital Clínico Quirúrgico Hermanos Almeijeiras a r and omized double blind clinical trial was carried out involving 52 patients who presented with painful migraine crises with or without prodromes . A group of 27 patients were given 6 mg of sumatriptan subcutaneously . Another group of 25 patients were given 1 mg of dihydroergotamine intramuscularly . It was seen that both drugs relieved the migrainous pain . However , sumatriptan did so in a greater percentage of patients . RESULTS AND CONCLUSIONS There was earlier , and also more complete , relief of pain in those patients receiving sumatriptan . With regard to side-effects of sumatriptan were pain at the back of the site of injection , sensation of pressure at the back of the neck , facial flushing and asthenia BACKGROUND Although various classes of medication are used to treat acute migraine in the emergency department ( ED ) , no treatment offers complete pain relief without side effects or recurrence of headache . Consequently , even though several antiemetic medications as well as SQ sumatriptan have demonstrated efficacy and tolerability for the ED treatment of migraine , there remains a need for more effective parenteral therapies . Open-label studies suggest that the combination of trimethobenzamide and diphenhydramine ( TMB/DPH ) may provide effective relief in a high proportion of migraineurs . OBJECTIVE To test the hypothesis that ED patients with acute migraine , given intramuscular TMB/DPH , would have a larger reduction in their pain scores than patients given SQ sumatriptan . METHODS This was an ED-based , r and omized , double-blind , " double-dummy " clinical trial comparing 2 parenteral treatments for acute migraine headaches . Subjects received a combination of TMB 200 mg and DPH 25 mg as a single intramuscular injection or 6 mg of SQ sumatriptan . Pain scores , disability scores , associated symptoms , and adverse effects were assessed for 2 hours in the ED and by telephone 24 hours after medication administration . The primary outcome was the between-group difference in reduction of pain intensity as measured by a vali date d numerical rating scale 2 hours after medication administration . This study was design ed to detect superiority of TMB/DPH ; therefore , a 1-tailed t-test was used . An interim analysis was planned to terminate the trial if predetermined endpoints in the primary outcome variable were reached . RESULTS The trial was stopped by the data monitoring committee after 40 subjects were enrolled because a substantial benefit in the primary outcome was found favoring sumatriptan . Baseline pain scores were comparable between the 2 groups . By 2 hours , sumatriptan subjects had improved by a mean of 6.1 and the TMB/DPH subjects had improved by a mean of 4.4 ( 95 % CI for difference of 1.7 : -0.1 to 3.4 ) . By 24 hours after medication administration , sumatriptan subjects had a mean improvement from baseline of 4.9 as compared to 5.3 for TMB ( 95 % CI for difference of -0.4 : -2.4 to 1.6 ) . The need for rescue medication was comparable between the groups . No serious or frequent adverse effects were noted in either group . CONCLUSIONS SQ sumatriptan is probably superior to TMB/DPH for treating the pain of acute migraine at 2 hours . However , TMB/DPH was well-tolerated , efficacious , and relieved pain comparably to sumatriptan at 24 hours . TMB/DPH might have a role in select population s in which sumatriptan is contraindicated or likely to be ineffective The efficacy of subcutaneous injection of sumatriptan in the acute treatment of migraine was assessed in a double-blind , r and omized , placebo-controlled cross-over study of 27 migraine patients . In addition , the patients were asked to give information about their well-being and subjective symptoms by means of a self-administered st and ardized question naire . A total of 22 migraine sufferers received a subcutaneous ( sc ) injection of 8 mg of sumatriptan and 24 received placebo . Of these patients , 19 received both treatments and thus completed the study . The primary efficacy end-point was a reduction in headache severity from severe or moderate to mild or no headache at 30 , 60 , 90 and 120 min . An effective response to treatment was achieved within 30 min in 63 % and within 60 min in 84 % of patients when treated with 8 mg sumatriptan sc , compared with 11 % for placebo ( p < 0.001 ) . Sumatriptan also provided significant relief from nausea and photophobia as compared with placebo . The proportion of patients that needed rescue medication after 120 min was significantly lower ( p < 0.001 ) with active treatment when compared with placebo . Sumatriptan was well tolerated and the majority of adverse events were mild and transient . The most frequent symptoms were those of malaise/fatigue or numbness . No changes in blood pressure or ECG readings were observed during the treatment . Compared with placebo , subcutaneous 8 mg sumatriptan also caused a substantial improvement in general well-being as revealed by the Minor Symptoms Evaluation Profile-acute ( MSEP-acute ) question naire . It is concluded that subcutaneous injection of sumatriptan is an effective , rapid-acting , and well-tolerated acute treatment for migraine attacks Although triptans have been proven effective for acute treatment of migraine , reserving them for moderate or severe pain may produce suboptimal pain relief and higher rates of recurrence . Recent evidence indicates that early intervention at the onset of pain improves outcomes . Post hoc analysis of a long-term , open-label European study of almotriptan 12.5 mg found that the percentage of attacks rendered pain-free at 2 hours was significantly greater when patients treated mild pain ( 84 % ) than when the intervention occurred during moderate or severe pain ( 53 % ) . A similar pattern emerged with respect to the consistency of pain relief , with a significant advantage for early intervention ( 88 % versus 56 % , respectively ) . A difference in favor of early intervention was also seen with respect to recurrence , need for rescue medication , and adverse events . The recurrence rate was significantly lower in patients treating mild pain ( 28 % ) than in those delaying treatment until the pain became moderate or severe ( 33 % ) , which suggests that achieving pain freedom results in less recurrence . These results were generally replicated in post hoc analysis of a subgroup of patients from a r and omized , placebo-controlled trial ( the Spectrum Study ) of oral sumatriptan 50 mg in migraineurs . This analysis demonstrated that with early intervention , pain was less likely to intensify , fewer attacks required redosing , more attacks remained pain-free 24 hours postdose , and normal function returned more quickly . In sum , early intervention with triptans can improve outcomes , avoiding much of the pain and disability associated with treating moderate or severe attacks OBJECTIVE Compare adult migraineurs ' health related quality of life to adults in the general U.S. population reporting no chronic conditions , and to sample s of patients with other chronic conditions . METHODS Subjects ( n = 845 ) were surveyed 2 - 6 months after participation in a placebo-controlled clinical trial and asked to complete a question naire including the SF-36 Health Survey , a migraine severity measurement scale and demographics . Results were adjusted for severity of illness and comorbidities . Scores were compared with responses to the same survey by the U.S. sample and by patients with other chronic conditions . RESULTS Response rate was 67 % . After adjustment for comorbid conditions , SF-36 scale scores were significantly ( P 0.001 ) lower in migraineurs , relative to age and sex-adjusted norms for the U.S. sample with no chronic conditions . Some health dimensions were more affected by migraine than other chronic conditions , while other dimensions were less affected by migraine . Measures of bodily pain , role disability due to physical health and social functioning discriminated best between migraineurs , the U.S. sample , and patients with other chronic conditions . Patients reporting moderate , severe and very severe migraines scored significantly ( P < or = 0.001 ) lower on five of the eight SF-36 scales than the U.S. sample . CONCLUSIONS Migraine has a unique , significant quality of life burden Naratriptan is a novel , potent agonist at the 5HT1B/1D receptor . A total of 335 migraine patients were treated in this r and omized , double-blind , placebo-controlled , dose-ranging , in-clinic study , to evaluate the efficacy , safety and tolerability of five doses of subcutaneous ( sc ) naratriptan ( 0.5 , 1 , 2.5 , 5 or 10 mg ) in comparison with sc sumatriptan ( 6 mg ) and placebo in the acute treatment of a moderate/severe migraine attack . Headache relief [ reduction of headache severity from moderate or severe ( grade 2/3 ) to mild or none ( grade 1/0 ) ] at 1 and 2 h after each dose , was reported by a statistically significantly higher proportion of patients for all doses of sc naratriptan and sc sumatriptan ( 6 mg ) than for placebo . The percentages of patients with headache relief at 2 h post-dose were : naratriptan ( 0.5 mg ) 65 % , ( 1 mg ) 75 % , ( 2.5 mg ) 83 % , ( 5 mg ) 94 % and ( 10 mg ) 91 % ; sumatriptan ( 6 mg ) 89 % ; placebo 41 % , ( P < 0.005 ) . The earliest report of a statistically significant difference compared with placebo for the times assessed was with sc naratriptan ( 10 mg ) at 10 min post-dose ( P = 0.023 ) . The percentages of patients reporting adverse events were dose-related ; sc naratriptan ( 0.5 mg ) 33 % , ( 1 mg ) 29 % , ( 2.5 mg ) 43 % , ( 5 mg ) 59 % and ( 10 mg ) 71 % ; sc sumatriptan 53 % ; placebo 22 % . There were no clinical ly significant changes in electrocardiogram ( ECG ) , vital signs or laboratory parameters . Systemic exposure increased proportionally to the dose , the absorption of sc naratriptan was rapid ( tmax = 10 min ) and the half-life was 5 h. In conclusion , sc naratriptan was an effective and well-tolerated acute treatment for migraine . Copyright 1998 Lippincott Williams & STUDY OBJECTIVE To assess the efficacy of SC sumatriptan injection versus placebo in the treatment of acute migraine in ED patients and that of open-label 100 mg sumatriptan PO tablets for recurrent migraine . DESIGN R and omized , double-blind , placebo-controlled , multi-center trial . SETTING Twelve EDs in the United States . PARTICIPANTS Adult patients presenting to the ED from September 1992 through April 1993 with a diagnosis of migraine as determined by International Headache Society criteria . Patients were r and omized to receive 6 mg sumatriptan SC or placebo . Patients were monitored for improvement in headache severity using a four-point scale and for time to meaningful relief using a stopwatch . The time to discharge from the ED was recorded . An open-label 100 mg sumatriptan PO tablet was given to all patients on discharge from the ED for use at home if the headache recurred within 24 hours . RESULTS One hundred thirty-six patients were enrolled . Seventy-five percent of patients treated with sumatriptan achieved meaningful relief compared with 35 % treated with placebo ( P < .001 ) . The median time to meaningful relief was 34 minutes in the group that received sumatriptan . Seventy percent of patients in the sumatriptan group versus 35 % in the placebo group reported mild or no pain at discharge ( P < .001 ) . Migraine-associated symptoms such as nausea , photophobia , and phonophobia were significantly reduced in the sumatriptan group ( P < .005 ) . The median time to discharge from the ED was shorter for the sumatriptan group than for the placebo group ( 60 versus 96 minutes , respectively ; P = .001 ) . At baseline , 15 % of patients in the sumatriptan group and 19 % of patients in the placebo group reported mild or no clinical disability . At the time of discharge , patients with mild or no disability increased to 75 % in the sumatriptan group compared with 44 % in the placebo group ( P = .001 ) . Fifty-seven of 92 patients ( 62 % ) with mild or no pain at discharge took open-label oral sumatriptan for headache recurrence , and 37 ( 65 % ) experienced meaningful relief within 2 hours . Median time to meaningful relief after oral sumatriptan was 65 minutes . CONCLUSION Sumatriptan ( 6 mg SC ) is effective in treating acute migraine in the ED . Oral sumatriptan ( 100 mg ) is effective in treating headache recurrence within 24 hours This study explored the association between headache response and return to functioning , and identified migraine-associated symptoms related to functional status and acceptability of migraine treatment as reported by patients . Data from migraineurs enrolled in the active arms of a r and omized , double-blind , parallel group , placebo-controlled , clinical trial were analysed . The relationships between headache response and functional response , and clinical factors and treatment acceptability were assessed using X 2 tests of proportions and logistic regressions . A greater proportion of patients with headache response at 0.5 h were functioning at 0.5 , 1 and 2 h compared with patients who did not attain a headache response at 0.5 h ( P < 0.0001 ) . These patients also were more likely to find their treatment acceptable ( P < 0.05 ) . The results suggest a direct temporal relationship among the key determinants of migraine resolution . Rapid headache response is associated with faster return to functioning ; rapid headache and functional responses are significant attributes of treatment acceptability BACKGROUND Migraine headaches result in significant patient suffering and high costs to managed care organizations and employers . Studies that evaluate patient outcomes and the financial consequences of migraine treatment are important from a clinical and an economic perspective . METHODS This prospect i ve , observational study assessed the outcomes of migraineurs in a mixed model staff/ independent practice association managed care organization for patients previously diagnosed as having migraine who received their first prescription for sumatriptan . Data collected included medical as well as pharmacy cl aims and patient surveys to measure changes in satisfaction , health-related quality of life , workplace productivity , and nonworkplace activity after sumatriptan therapy was initiated . RESULTS A total of 178 patients completed the study . Results showed significant decreases in the mean number of migraine-related physician office visits , emergency department visits , and medical procedures in the 6 months after sumatriptan therapy compared with the 6 months before sumatriptan was used ( P<.05 ) . Four of the health-related quality -of-life dimensions and the physical component summary score measured by the SF-36 ( which is a valid , reliable general health status instrument ) showed significant improvements at 6 months compared with patients ' scores before use of sumatriptan ( P<.05 ) . Health-related quality of life measured by the disease-specific instrument MSQ ( Migraine-Specific Quality of Life Question naire-Version 1.0 , 1992 Glaxo Wellcome Inc , Research Triangle Park , NC ) showed significant improvement at 3 and at 6 months compared with baseline scores ( P<.05 ) . There were also improvements in patient satisfaction and significant reductions in time lost from workplace productivity and nonworkplace activity . CONCLUSION In the 6 months after sumatriptan therapy was initiated , health care re source use and time lost from workplace productivity and nonworkplace activity were reduced , while health-related quality of life and patient satisfaction scores improved for the managed care migraineurs enrolled in this study OBJECTIVE To determine the effect of sumatriptan on migraine-related workplace productivity loss . PATIENTS AND METHODS In this r and omized , double-blind , placebo-controlled , parallel-group trial , adult migraineurs self-injected 6 mg of sumatriptan or matching placebo to treat a moderate or severe migraine within the first 4 hours of a minimum of an 8-hour work shift . Outcome measures included productivity loss and number of patients returning to normal work performance 2 hours after injection and across the work shift , time to return to normal work performance , and time to headache relief . RESULTS A total of 206 patients underwent screening , 140 ( safety population ) of whom returned for clinic treatment . Of these 140 patients , 119 received migraine treatment in the workplace ( intent-to-treat population ) , 116 of whom comprised the study population . Of these 116 patients , 76 self-administered sumatriptan , and 40 self-administered placebo . Sumatriptan treatment tended to reduce median productivity loss 2 hours after injection compared with placebo ( 25.2 vs 29.9 minutes , respectively ; P = .14 ) . Significant reductions in productivity loss were obtained across the work shift after sumatriptan treatment compared with placebo ( 36.8 vs 72.6 minutes , respectively ; P = .001 ) . Significantly more sumatriptan-treated patients vs placebo-treated patients experienced shorter return to normal work performance at 2 hours ( 53/76 [ 70 % ] vs 12/40 [ 30 % ] , respectively ) and across the work shift ( 64/76 [ 84 % ] vs 23/40 [ 58 % ] , respectively ; P < .001 ) . Significantly more sumatriptan-treated patients experienced headache relief 1 hour after injection compared with placebo-treated patients ( 48/76 [ 63 % ] vs 13/40 [ 33 % ] , respectively ; P = .004 ) . CONCLUSION Across an 8-hour work shift , sumatriptan was superior to placebo in reducing productivity loss due to migraine OBJECTIVE To evaluate efficacy and tolerability of subcutaneous sumatriptan 6 mg versus placebo for acute migraine between ethnic groups . BACKGROUND Patients in previous sumatriptan studies have been predominantly Caucasian and the effects of sumatriptan between different ethnic groups are unknown . METHODS This was a multicenter , 3-phase , 12-attack study . Phases I and III ( inclinic ) were r and omized , double-blind , placebo-controlled , crossover design s. Phase II ( outpatient ) was a single-blind design . Sumatriptan was compared to placebo across 2 groups ( non-Caucasian and Caucasian ) and individual ethnic subgroups ( black , Hispanic , and others ) . Headache response , pain-free response , associated symptoms , and clinical disability were assessed . Tolerability assessment s included the incidence of adverse events , physical examinations , vital signs , electrocardiograms , and clinical laboratory data . RESULTS Two hundred patients treated at least one migraine attack ( 150 non-Caucasians : 46 blacks , 68 Hispanics , 36 others ) . Two hours postdose , significantly more inclinic sumatriptan-treated patients reported headache response ( non-Caucasians , 81 % versus 37 % placebo ; Caucasians , 87 % versus 19 % placebo ; P<.001 ) and mild or no clinical disability , compared with placebo ( non-Caucasians , 87 % versus 50 % placebo ; Caucasians , 90 % versus 38 % placebo ; P<.001 ) . Blacks ( 80 % ) , Hispanics ( 83 % ) , and others ( 74 % ) reported similar patterns of headache response at 2 hours . Similar results were reported during the outpatient phase . The incidence of adverse events following sumatriptan during the inclinic phase was similar between ethnic groups ( non-Caucasian , 75 % ; Caucasian , 79 % ) and higher than placebo ( non-Caucasian , 51 % ; Caucasian , 31 % ) . Overall , adverse events in the outpatient phase of the study were lower than in the inclinic phase . CONCLUSION Sumatriptan injection is effective and well tolerated in non-Caucasians and Caucasians for the treatment of acute migraine attacks . Only minor differences in efficacy or tolerability were observed between blacks , Hispanics , and others This double-blind , placebo-controlled , parallel-group , multicentre , multinational , phase-III trial was design ed to assess the efficacy and safety of a single subcutaneous injection of placebo , 2 doses of alniditan ( 1.4 mg and 1.8 mg ) and 6 mg of sumatriptan in subjects with acute migraine . A total of 114 investigators from 13 different countries screened 2021 subjects . In total 924 patients were treated with placebo ( 157 ) , alniditan 1.4 mg ( 309 ) , alniditan 1.8 mg ( 141 ) and sumatriptan 6 mg ( 317 ) . The lower number of subjects in the alniditan 1.8 mg group is due to the termination of this trial arm after the incidence of a serious adverse event and a subsequent protocol amendment . The number of subjects who were pain free at 2 h ( primary endpoint ) was : 22 ( 14.1 % ) with placebo , 174 ( 56.3 % ) with alniditan 1.4 mg , 87 ( 61.7 % ) with alnditan 1.8 mg and 209 ( 65.9 % ) with sumatriptan 6 mg . Alniditan 1.4 mg was significantly better ( P < 0.001 ) than placebo and sumatriptan was significantly better ( P = 0.015 ) than alniditan 1.4 mg . The number of responders ( reduction of headache severity from moderate or severe headache before treatment to mild or absent at 2 h ) , was 59 ( 37.8 % ) on placebo , 250 ( 80.9 % ) on alniditan 1.4 mg , 120 ( 85.1 % ) on alniditan 1.8 mg , and 276 ( 87.1 % ) on sumatriptan . Response was significantly higher ( P < 0.001 ) with alniditan 1.4 mg than with placebo , and significantly lower ( P = 0.036 ) with alniditan 1.4 mg than with sumatriptan . Recurrence rates were : 22 ( 37.3 % ) with placebo , 87 ( 34.8 % ) with alniditan 1.4 mg , 35 ( 29.2 % ) with alniditan 1.8 mg and 108 ( 39.1 % ) with sumatriptan . Adverse events occurred in 577/924 ( 62.4 % ) subjects , i.e. in 62/157 ( 39.5 % ) with placebo , 214/309 ( 69.3 % ) with alniditan 1.4 mg , 91/141 ( 64.5 % ) with alniditan 1.8 mg and 210/317 ( 66.2 % ) with sumatriptan 6 mg . Sumatriptan was significantly better than alniditan 1.4 mg for pain free at 2 h. The difference , however , was small and clinical ly not important . For alniditan , a dose-dependent adverse event relationship was seen . The safety profile of alniditan 1.4 mg was similar to that of sumatriptan & 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 Glutamatergic hyperactivity is implicated migraine pathogenesis . Also , LY293558 , an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate ( KA ) receptor antagonist , is effective in pre clinical models of migraine . We therefore tested LY293558 in acute migraine . We conducted a r and omized , triple-blind , parallel-group , double-dummy , multicentre trial of 1.2 mg/kg intravenous ( IV ) LY293558 , 6 mg subcutaneous ( SC ) sumatriptan , or placebo in the treatment of acute migraine . The primary efficacy variable was the headache response rate , i.e. headache score improvement from moderate/severe at baseline to mild/none at 2 h. Of 45 enrolled patients , 44 patients ( 20M:24F ; mean age ± SD = 40 ± 9 years ) completed the study . Response rates were 69 % for LY293558 ( P = 0.017 vs. placebo ) , 86 % for sumatriptan ( P < 0.01 vs. placebo ) and 25 % for placebo . LY293558 and sumatriptan were superior to placebo ( P < 0.01 for all comparisons ) on all other measures of improvement in pain and migraine associated symptoms . Fifteen percent of patients who took LY293558 reported adverse events ( AEs ) ( n = 2 ; one mild , one severe ) . Fifty-three percent of patients who took sumatriptan ( n = 8 ; seven mild , one moderate ) and 31 % of those who received placebo reported AEs ( n = 5 ; four mild , one severe ) . The efficacy and safety results of LY293558 in this small migraine proof of concept trial , together with supportive pre clinical data , provide evidence for a potential role of nonvasoactive AMPA/KA antagonists in treating migraine . Larger trials are needed to further test the hypothesis Sumatriptan succinate , a 5-HT1D receptor agonist , constricts human cranial arteries . Two parallel-group trials for treatment of acute migraines were conducted in the United States . Adult patients were r and omized and given either 6 mg of sumatriptan succinate subcutaneously ( n = 734 ) or placebo ( n = 370 ) . At 1 hour , sumatriptan was significantly more effective than placebo in reducing moderate or severe headache pain to mild or no pain ( 70 % vs 22 % ) , in completely relieving headaches ( 49 % vs 9 % ) , and in improving clinical disability ( 76 % vs 34 % ) . Sumatriptan also reduced nausea and photophobia significantly better than placebo . Patients with residual migraines received another injection ; those who had originally received sumatriptan received either a second active injection ( n = 187 ) or placebo ( n = 178 ) , while those who had received placebo received a second placebo injection ( n = 335 ) . Statistical evidence for benefit of second sumatriptan injection is absent . Adverse events associated with sumatriptan were tingling , dizziness , warm-hot sensations , and injection-site reactions . Sumatriptan is effective and well tolerated in patients with acute migraine Sumatriptan , a specific serotonin1-like receptor agonist , was studied in the acute treatment of migraine . Two hundred forty-two adult migraineurs participated in a r and omized , double-blind study in which one dose of 1 , 2 , 3 , 4 , 6 , or 8 mg of subcutaneous sumatriptan succinate was evaluated in sequential ascending fashion . At each dose level , a placebo group was included . Efficacy was defined as reduction of moderate or severe pain to mild or no pain , without the use of rescue medication . Headache relief rates showed an approximate dose-response relationship and at 1 hour were as follows : placebo , 24 % ; 1 mg , 43 % ; 2 mg , 57 % ; 3 mg , 57 % ; 4 mg , 50 % ; 6 mg , 73 % ; and 8 mg , 80 % . Relief of nausea and improvement in clinical disability were also approximately dose related . Adverse events were dose related ; the most common types were injection site reactions and tingling . The 6-mg dose was as effective as the 8-mg dose but was associated with fewer adverse effects and so is optimal The efficacy and tolerability of subcutaneous ( SC ) sumatriptan administered with the IMITREX ( sumatriptan succinate ) STATdose System , which circumvents the need for patients or health care professionals to h and le a syringe , were evaluated in two r and omized , double-masked , parallel-group , placebo-controlled , multicenter studies . In the clinic , 158 adults with migraine diagnosed according to International Headache Society criteria received SC sumatriptan ( 6 mg ) or placebo delivered with the IMITREX STATdose System for treatment of a migraine attack . By 120 minutes after SC dosing , 73 % and 79 % of sumatriptan-treated patients , compared with 28 % and 37 % of placebo-treated patients in studies 1 and 2 , respectively , experienced headache relief ( a statistically significant difference ) . Clinical disability scores 120 minutes after dosing showed that 75 % and 85 % of sumatriptan-treated patients , compared with 30 % and 42 % of placebo-treated patients , were normal or only mildly impaired ( a statistically significant difference ) . Similar efficacy rates were observed for nausea , phonophobia , and photophobia . No serious or unusual adverse events occurred , and no clinical ly relevant abnormalities in laboratory test values were reported . Based on these results , we concluded that SC sumatriptan ( 6 mg ) administered using the IMITREX STATdose System is effective for the treatment of migraine . The efficacy and tolerability profiles of SC sumatriptan administered with this device are similar to those reported for SC sumatriptan administered with a conventional syringe OBJECTIVE The aim of this study was to evaluate the efficacy and tolerability of a single 4-mg dose of sumatriptan SC for the acute treatment of adult patients experiencing a migraine attack with moderate to severe pain . METHODS In this r and omized , double-blind , placebo-controlled study , subjects included men and women aged 18 to 60 years who had migraine with or without aura , as defined by the 1988 International Headache Society criteria . Subjects received either sumatriptan 4 mg SC or placebo SC for a migraine attack with headache pain of moderate to severe intensity . The primary efficacy measurement was pain relief at 2 hours . Secondary efficacy measures included the severity of headache pain at 10 , 20 , 30 , 40 , 50 , 60 , and 90 minutes postadministration . Clinical assessment s of pain severity and adverse events were made by way of question ing and observation of subjects and were completed at 10 , 20 , 30 , 40 , 50 , 60 , 90 , and 120 minutes postadministration . RESULTS Five hundred seventy-seven subjects ( 87 % female and 94 % white ) participated in this study . Three hundred eighty-four received sumatriptan and 193 received placebo . At 120 minutes postadministration , sumatriptan 4 mg SC was associated with greater proportions of patients who experienced pain relief ( 70 % vs 22 % ; P<0.001 ) or were pain free ( 50 % vs 11 % ; P<0.001 ) . In addition , there were statistically significant differences between sumatriptan 4 mg SC and placebo for multiple secondary end points , including pain relief as early as 10 minutes postadministration ( 11 % vs 6 % ; P=0.039 ) , pain-free status as early as 30 minutes postadministration ( 10 % vs 3 % ; P<0.001 ) , nausea as early as 30 minutes postadministration ( 39 % vs 49 % ; P=0.021 ) , and photophobia as early as 10 minutes postadministration ( 80 % vs 87 % ; P=0.046 ) . The most common adverse events in the sumatriptan 4-mg SC and placebo groups , respectively , were injection-site reactions ( 43 % and 15 % ) , tingling ( 12 % and 3 % ) , dizziness or vertigo ( 10 % and 5 % ) , and warm or hot sensation ( 8 % and 2 % ) . Treatment groups were not statistically compared for adverse events . CONCLUSIONS Sumatriptan 4 mg SC was effective for the acute treatment of migraine attacks and was generally well tolerated in these patients OBJECTIVES To evaluate the efficacy of self-administered subcutaneous sumatriptan in the acute treatment of early-morning migraine attacks . DESIGN A double-blind , r and omized , placebo-controlled , cross-over study . SETTING Thirteen neurology centres in France . SUBJECTS Patients of either sex , 18 - 65 years old , with two to six attacks of migraine ( according to the International Headache Society ( IHS ) criteria , with or without aura ) per month , of which at least two had to be early-morning migraine attacks . One-hundred- and -one patients were included , 96 being evaluable for the first attack and 81 for the cross-over design . INTERVENTIONS Two migraine attacks ( grade 2/3 ) were treated with sumatriptan ( 6 mg ) or placebo , with an optional second injection 1 - 24 h later . Main outcome measures . The primary end-point was headache relief : reduction in headache severity from grade 2/3 ( moderate/severe ) to grade 1/0 ( mild/none ) 2 h after treatment . RESULTS Sumatriptan was superior to placebo for headache relief ( 32 [ 78 % ] vs. 11 [ 28 % ] at the first attack ; 29 [ 73 % ] vs. 8 [ 20 % ] at the second ; P < 0.001 ) . Because of a significant carry-over effect for some of the secondary end-points , a parallel-group analysis of the first attack was performed , which confirmed a significantly higher efficacy of sumatriptan for all end-points : pain-free rate ( 22 [ 46 % ] vs. 7 [ 15 % ] ; P = 0.001 ) and use of a second injection ( 26 [ 53 % ] vs. 38 [ 81 % ] ; P = 0.004 ) . Sumatriptan was preferred by 74 % of patients vs. 17 % for placebo , and 9 % expressed no preference ( P < 0.0001 ) . After complete relief , headache reappeared in 8/23 ( 35 % ) patients with sumatriptan and 3/7 ( 43 % ) with placebo . Adverse events were significantly more frequent with sumatriptan but they were minor and transient . CONCLUSION Subcutaneous sumatriptan auto-injection is an effective and well-tolerated acute treatment of early-morning migraine attacks allowing earlier return to normal activity A novel self-injector for the administration of subcutaneous sumatriptan in the treatment of migraine attacks was tested in 138 patients recruited by family physicians in Denmark ; 108 patients completed the initial double-blind , crossover part of the study . Sumatriptan 6 mg s.c . was significantly better than placebo at 30 , 60 , 90 and 120 min after injection in relieving moderate or severe headache to mild or none as well as relieving any headache to none . At 60 min after injection , the treatment response rate was 61 % for sumatriptan and 6 % for placebo . During the following open-phase trial of four attacks treated with sumatriptan , treatment response rates were 68–74 % . During the total of 538 attacks treated , 12 attempts at using the self-injector failed . In the double-blind and open phases , 81 % and 90 % of patients respectively found the device easy or very easy to use . Adverse effects were benign and short-lasting , but led seven patients to discontinue the study . In conclusion , subcutaneous sumatriptan administered with a novel self-injector is an effective treatment for migraine compared to placebo in patients treated by their family physician Objective : To compare the efficacy of 20 mg of IV metoclopramide , given up to four times over 2 hours as needed for persistent headache , with 6 mg of subcutaneous sumatriptan for the emergency department treatment of migraine headaches . Methods : This was a r and omized , double-blind , clinical trial with two intervention arms . The primary endpoint was change in pain intensity as measured by an 11-point pain scale at 2 hours . Secondary endpoints included change in pain intensity at 24 hours and rates of pain-free headache relief at 2 and 24 hours . Results : Two hundred two patients were screened , and 78 of 91 eligible patients were r and omized . The two groups had comparable pain scores at baseline . By 2 hours , the change in pain intensity for the metoclopramide group was 7.2 compared with 6.3 for the sumatriptan group ( 95 % CI for difference : −0.2 to 2.2 ) . When compared at 24 hours , the metoclopramide group had improved by 6.1 compared with baseline and the sumatriptan group had improved by 5.0 ( 95 % CI for difference : −0.6 to 2.8 ) . At 2 hours , pain-free rates were 59 % in the metoclopramide arm and 35 % in the sumatriptan arm ( 95 % CI for difference of 24 % : 2 to 46 % ) . The most common side effects at both time points were weakness , dizziness , and drowsiness , which were distributed evenly between the two groups . There were no reports of chest pain within the first 2 hours . The incidence of restlessness , stiffness , and abnormal movements was distributed equally between the two groups . Conclusions : When compared at 2 and 24 hours , aggressive ( 20 mg dosed up to four times ) IV metoclopramide and 6 mg of subcutaneous sumatriptan relieved migraine headache pain comparably . Some secondary endpoints suggest that metoclopramide may be the preferable therapy for migraines presenting to the emergency department AIM To assess the effectiveness of subcutaneous sumatriptan ( 4 mg ) in the acute treatment of migraine . METHODS A r and omised , double-blind , placebo controlled study was conducted in four New Zeal and centres . On developing an acute attack of migraine , patients attended a centre where they were given either sumatriptan 4 mg or placebo by subcutaneous injection . Headache severity and clinical disability were measured over a 2 hour period . RESULTS Fifty-one patients , aged 19 - 58 years with common or classical migraine were treated . Twenty-eight patients received 4 mg sumatriptan and 23 patients received placebo . Pretreatment headache severity was grade d moderate in 76 % and severe in 24 % . Thirty-two percent of patients were sufficiently disabled to require bed rest and a further 48 % had severe impairment of working ability . Sumatriptan was significantly more effective than placebo in relieving or reducing headache severity after 30 minutes . Sixty-four percent improved on sumatriptan compared to 27 % on placebo . Functional disability , nausea , vomiting and photophobia were also greatly reduced . Adverse effects occurred in 17 % of patients receiving placebo , and 82 % receiving sumatriptan , the commonest being injection site reactions . CONCLUSION Subcutaneous sumatriptan 4 mg is an effective and well-tolerated acute treatment in adult patients with moderate to severe common or classical migraine . The efficacy rate of 64 % is lower than that found in recent controlled studies using a higher dose The efficacy and safety of sumatriptan , a selective 5-HT1-like receptor agonist , were studied in a r and omized , double-blind , placebo-controlled , parallel-group , multicentre , multinational clinical trial of 235 patients suffering a moderate to severe migraine attack . Patients were r and omized to treat a single migraine attack at home with 6 mg sumatriptan or placebo using an auto-injector . If the migraine had not improved at 1 h , patients had the option of taking a second identical injection . The primary measure of treatment efficacy was based on a comparison of the number of patients in the two treatment groups who had a reduction in headache severity from severe or moderate to mild or none at 1 and 2 h. At 1 h , 77 % of patients treating with 6 mg sumatriptan compared to 26 % treating with placebo ( p less than 0.001 ) had mild headache or none . At 2 h , the response rates for all patients had risen to 83 and 30 % , respectively . Of those patients requiring a second dose at 1 h , improvement to mild or no headache at 2 h was achieved in 61 % of patients receiving sumatriptan compared to 15 % of those receiving placebo . Other migraine symptoms were more effectively treated by sumatriptan and patients were able to return to work or normal activities earlier . Migraine recurrence within 48 h was a feature of 46 % of attacks treated by patients with either treatment . Adverse events were more frequent using sumatriptan but were minor and transient . ( ABSTRACT TRUNCATED AT 250 WORDS BACKGROUND The headache in migraine attacks may be caused by dilatation of certain cranial arteries or arteriovenous anastomoses , by neurogenic dural plasma extravasation , or by both of these mechanisms . Sumatriptan , a novel selective agonist of 5-hydroxytryptamine-like receptors , blocks these phenomena . We investigated its efficacy in migraine . METHODS We studied 639 patients with migraine attacks in a r and omized , double-blind , placebo-controlled , parallel-group clinical trial . We assessed the effect of subcutaneous injections of 6 or 8 mg of sumatriptan or placebo on the severity of headache and associated migrane symptoms 30 , 60 , and 120 minutes after treatment . Patients who were not free of pain after 60 minutes subsequently received placebo if they had initially received placebo or 8 mg of sumatriptan , and 6 mg of sumatriptan or placebo if they had initially received 6 mg of sumatriptan . RESULTS After 60 minutes , the severity of headache was decreased in 72 percent ( 95 percent confidence interval , 68 to 76 percent ) of the 422 patients given 6 mg of sumatriptan , 79 percent ( 95 percent confidence interval , 71 to 87 percent ) of the 109 patients given 8 mg of sumatriptan , and 25 percent ( 95 percent confidence interval , 17 to 33 percent ) of the 105 patients given placebo ( data on 3 patients could not be evaluated ) . As compared with the placebo group , 47 percent ( 95 percent confidence interval , 38 to 57 percent ) more patients who had received 6 mg of sumatriptan and 54 percent ( 95 percent confidence interval , 43 to 65 percent ) more patients who had received 8 mg of sumatriptan had a decrease in the severity of headache ( P less than 0.001 for both comparisons ) . After 120 minutes , 86 to 92 percent of the 511 patients treated with sumatriptan ( 202 assigned to 6 mg plus placebo , 203 to 6 mg plus 6 mg , and 106 to 8 mg plus placebo ) had improvement in the severity of headache , as compared with only 37 percent of the 104 patients who received placebo once or twice ( P less than 0.001 for all comparisons ) . Twenty-one patients were excluded from the analysis because of missing data ( 19 ) or protocol violations ( 2 ) . The response rates did not differ significantly among the sumatriptan regimens . Adverse events were minor and transient in all groups . CONCLUSIONS We conclude that a single 6-mg dose of sumatriptan given subcutaneously is a highly effective , rapid-acting , and well-tolerated treatment for migrane attacks . The administration of a second dose 60 minutes later to patients not responding well to an initial dose affords little additional benefit |
12,130 | 25,048,608 | There is increasing evidence that for many techniques , short-term maternal outcomes are equivalent . | BACKGROUND Caesarean section is a common operation .
Techniques vary depending on both the clinical situation and the preferences of the operator .
OBJECTIVES To compare the effects of 1 ) different types of uterine incision , 2 ) methods of performing the uterine incision , 3 ) suture material s and technique of uterine closure ( including single versus double layer closure of the uterine incision ) on maternal health , infant health , and healthcare re source use .
AUTHORS ' CONCLUSIONS Caesarean section is a common procedure performed on women worldwide . | BACKGROUND Variations exist in the surgical techniques used for caesarean section and many have not been rigorously assessed in r and omised controlled trials . We aim ed to assess whether any surgical techniques were associated with improved outcomes for women and babies . METHODS CORONIS was a pragmatic international 2 × 2 × 2 × 2 × 2 non-regular fractional , factorial , unmasked , r and omised controlled trial that examined five elements of the caesarean section technique in intervention pairs . CORONIS was undertaken at 19 sites in Argentina , Chile , Ghana , India , Kenya , Pakistan , and Sudan . Each site was assigned to three of the five intervention pairs : blunt versus sharp abdominal entry ; exteriorisation of the uterus for repair versus intra-abdominal repair ; single-layer versus double-layer closure of the uterus ; closure versus non-closure of the peritoneum ( pelvic and parietal ) ; and chromic catgut versus polyglactin-910 for uterine repair . Pregnant women were eligible if they were to undergo their first or second caesarean section through a planned transverse abdominal incision . Women were r and omly assigned by a secure web-based number allocation system to one intervention from each of the three assigned pairs . All investigators , surgeons , and participants were unmasked to treatment allocation . The primary outcome was the composite of death , maternal infectious morbidity , further operative procedures , or blood transfusion ( > 1 unit ) up to the 6-week follow-up visit . Women were analysed in the groups into which they were allocated . The CORONIS Trial is registered with Current Controlled Trials : IS RCT N31089967 . FINDINGS Between May 20 , 2007 , and Dec 31 , 2010 , 15 935 women were recruited . There were no statistically significant differences within any of the intervention pairs for the primary outcome : blunt versus sharp entry risk ratio 1·03 ( 95 % CI 0·91 - 1·17 ) , exterior versus intra-abdominal repair 0·96 ( 0·84 - 1·08 ) , single-layer versus double-layer closure 0·96 ( 0·85 - 1·08 ) , closure versus non-closure 1·06 ( 0·94 - 1·20 ) , and chromic catgut versus polyglactin-910 0·90 ( 0·78 - 1·04 ) . 144 serious adverse events were reported , of which 26 were possibly related to the intervention . Most of the reported serious adverse events were known complications of surgery or complications of the reasons for the caesarean section . INTERPRETATION These findings suggest that any of these surgical techniques is acceptable . However , longer-term follow-up is needed to assess whether the absence of evidence of short-term effects will translate into an absence of long-term effects . FUNDING UK Medical Research Council and WHO OBJECTIVE A new technical variant of caesarean section was described a few years ago , which is characterised by blunt surgical preparation and simplified seam technique . A prospect i ve investigation compared the differences in the surgery and postoperative process as well as the rate of complications between this Misgav Ladach method and the conventional technique of Sectio . The individual postoperative well-being of the women was recorded by visual analog scales . - PATIENTS AND METHODS Women , whom realize the including criteria s ( first caesarean section , > /= 32 . week of pregnancy , one baby ) , were examined in this study over one year : 105 patients operated with the Misgav Ladach method and 67 conventionally operated patients . The patients were r and omized in a function of the first letter of the surname ( A-K : Misgav-Ladach method ; L-Z : classical technique ) . - RESULTS The surgical time from the cut to the seam was significantly shorter ( 29.8 vs. 49.3 min ; p < 0,001 ) in the Misgav Ladach group . There were no differences between the two methods in the rate of postoperative complications . The febrile morbidity was equivalent in both groups ( 7.6 % vs. 9 % ) , likewise the frequency of postoperative hematomas ( 3.8 % vs. 3 % ) . The postoperative period with consumption of analgetics was significantly longer in the group of conventionally operated patients ( 1.9 d vs. 2.4 d ; p < 0.01 ) . The postoperative presentness was estimated significantly better ( p < 0,.01 ) by the patients of the Misgav ladach group - probably caused by the significantly earlier mobilization ( p < 0.05 ) . - CONCLUSION The surgical technique described by Misgav and Ladach allows a safe execution of the caesarean section and represents an alternative to the conventional method . The duration of operation ( cut-seam-time ) was significantly shorter . The technique of less traumatising of tissue caused a significantly earlier mobilisation and a significantly shorter requirement of analgetics . The women estimated her postoperative physical condition as better 125 caesarean sections were performed at the Department of Obstetrics and Gynecology , Allgemeines Krankenhaus Celle , during the last 6 months of 1991 . The caesarean section rate was 13.4 % ( 930 deliveries in that period).--For closure of the uterotomy a two-layer suture was applied ( 62 patients ) as well as a one-layer suture , the modified Sarafoff suture ( 63 patients ) . Both techniques were used alternatively . We compared intraoperative and postoperative courses of the two groups of patients in a prospect i ve study . Between the 8th and 10th day after surgery an ultrasonic examination of the scar was performed . The data in both groups did not show any significant difference , except that the scar in the one-layer group was thinner .-- So , our results did not support an advantage of the one-layer suture as compared to the two-layer technique Aim . To compare Pfannenstiel-Kerr ( PKM ) and Misgav-Ladach ( MLM ) methods in terms of operation-related features and neonatal outcome in primary cesarean deliveries . Methods . A total of 180 pregnant women r and omized into PKM ( n = 90 ) or MLM ( n = 90 ) groups were included in this study . Primary outcome measures were total operative and extraction times , Apgar score , blood loss , wound complications , and the suture use . Secondary outcome measures were wound seroma and infection incidence , time of bowel restitution , and the perceived pain . Results . Total operation and extraction times were significantly shorter and less suture material was used in the MLM group than the PKM group ( p < 0.001 ) . Initially , higher scores obtained for 6 h-VAS in the MLM group ( p < 0.05 ) were normalized after 24 h of the operation . PKM and MLM were similar in terms of preoperative and postoperative levels of hemoglobin and hematocrit , wound complication , bowel restitution , fever , seroma , infection , wound dehiscence and the need for transfusion , antibiotic , and analgesics . Conclusion . The operation-related morbidity of the MLM and PKM for primary C/S seem to be comparable ; however , the MLM seems to be superior in terms of operation time and the amount of suture usage but inferior in pain scores in the early postoperative period OBJECTIVE To compare the effect of different suturing techniques in repeat caesarean section in terms of scar thickness , blood loss , operative time and scar dehiscence at the time of next caesarean section . STUDY DESIGN A r and omized double blinded trial . PLACE AND DURATION OF STUDY Obstetrics and Gynaecology Department of Bahawal Victoria Hospital , Bahawalpur , from June 2005 to June 2010 . METHODOLOGY Ninety patients undergoing repeat caesarean section were included and r and omly assigned to one of the three groups . Group A underwent one layer closure ; Group B underwent two layer closure while Group C underwent modified two layer closure of the uterine incision . Ultrasonographic evaluation of the scar thickness was performed at 6 weeks post operatively and longer follow-up was done in next caesarean for scar dehiscence . Frequency percentages were obtained and compared using chi-square test with significance at p < 0.05 . RESULTS In only 2 ( 6.6 % ) of modified two layer closure cases , it was necessary to use additional haemostatic sutures , compared with 16 ( 53 % ) of one layer closure group , and 10 ( 33 % ) of the two layer closure group . At 6 weeks , the mean car thickness in group C ( 17.08 + 1.635 mm ) was significantly greater ( p < 0.001 ) as compared to group A ( 13.19 + 1.32 mm ) and group B ( 14.58 + 1.18 mm ) . At long-term follow-up , only 1 ( 6 % ) case from group C showed the " uterine window " at the time of repeat caesarean section as compared to 3 ( 23 % ) in group A and 2 ( 14 % ) in group B. CONCLUSION Scar thickness was significantly increased with modified two layer closure when compared with traditional one and two layer closure of lower transverse uterine incision at the time of repeat caesarean section Design CORONIS is a pragmatic multicentre fractional factorial r and omised controlled trial and is being conducted in sites in Argentina , Chile , Ghana , India , Kenya , Pakistan and Sudan [ 1 ] . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out using a 2 balanced incomplete block factorial design . Each woman is allocated THREE of the five pairs of interventions using a bespoke secure webbased r and omisation system ( with 24/7 automated backup telephone system ) hosted by the NPEU Clinical Trials Unit . The 5 pairs of interventions are : i. Blunt versus sharp abdominal entry ii . Exteriorisation of the uterus for repair versus intraabdominal repair iii . Single versus double layer closure of the uterus iv . Closure versus non-closure of the peritoneum ( pelvic and parietal ) v. Chromic catgut versus Polyglactin-910 for uterine repair Primary outcome : death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures or blood transfusion . Sample size required : 15,000 women in total ; minimum 9,000 women per comparison pair In recent years Stark and colleagues ( 1 , 2 ) proposed the application to the cesarean section of a number of new surgical techniques adopted from various sources : the differences with respect to the traditional procedures were the Joel-Cohen methods for opening the abdomen , suturing the uterus in one layer , and non-closure of the visceral and parietal peritoneal layers . They demonstrated that this cesarean section procedure is safe , fast and has a low risk of postoperative complications in the mothers ( 2 ) and therefore this technique has been adopted in many centers . Nevertheless , the possible consequences of these changes on the short-term outcome of the newborn have never been evaluated . Cesarean section and maternal anesthesia are risk factors for the respiratory distress syndrome , transient tachypnea and respiratory depression in the newborn infants ( 3 ) and , therefore , we wanted to evaluate if a cesarean section technique presumably faster than the traditional procedure could improve the short-term outcome of the newborns Background Caesarean section is one of the most commonly performed operations on women throughout the world . Rates have increased in recent years – about 20–25 % in many developed countries . Rates in other parts of the world vary widely . A variety of surgical techniques for all elements of the caesarean section operation are in use . Many have not yet been rigorously evaluated in r and omised controlled trials , and it is not known whether any are associated with better outcomes for women and babies . Because huge numbers of women undergo caesarean section , even small differences in post-operative morbidity rates between techniques could translate into improved health for substantial numbers of women , and significant cost savings . Design CORONIS is a multicentre , fractional , factorial r and omised controlled trial and will be conducted in centres in Argentina , Ghana , India , Kenya , Pakistan and Sudan . Women are eligible if they are undergoing their first or second caesarean section through a transverse abdominal incision . Five comparisons will be carried out in one trial , using a 2 × 2 × 2 × 2 × 2 fractional factorial design . This design has rarely been used , but is appropriate for the evaluation of several procedures which will be used together in clinical practice . The interventions are : • Blunt versus sharp abdominal entry • Exteriorisation of the uterus for repair versus intra-abdominal repair • Single versus double layer closure of the uterus • Closure versus non-closure of the peritoneum ( pelvic and parietal ) • Chromic catgut versus Polyglactin-910 for uterine repair The primary outcome is death or maternal infectious morbidity ( one or more of the following : antibiotic use for maternal febrile morbidity during postnatal hospital stay , antibiotic use for endometritis , wound infection or peritonitis ) or further operative procedures ; or blood transfusion . The sample size required is 15,000 women in total ; at least 7,586 women in each comparison . Discussion Improvements in health from optimising caesarean section techniques are likely to be more significant in developing countries , because the rates of postoperative morbidity in these countries tend to be higher . More women could therefore benefit from improvements in techniques . Trial registration The CORONIS Trial is registered in the Current Controlled Trials registry . ISCRTN31089967 OBJECTIVE The aim of the study was to evaluate the outcome of two different methods of cesarean section . To determine whether the Misgav-Ladach caesarean technique can offer benefits when compared with conventional Pfannenstiel caesarean section technique . STUDY DESIGN This study describes operative details and the postoperative course of 110 patients who underwent caesarean section in May 2000 to December 2000 in Department of Gynecology and Obstetrics in Regional Hospital in Slupsk , Pol and . METHOD One group ( 50 women ) was operated with the Misgav-Ladach method for caesarean section and the other group ( 60 women ) with Pfannenstiel method . RESULTS Operating time was significantly different between the two methods , with an average of 20.2 minutes with the Misgav-Ladach method and 47.3 minutes with the Pfannenstiel method ( p < 0.001 ) . Time of child delivery was with average 1.1 minutes with the Misgav-Ladach method and 3.8 minutes with the Pfannenstiel method ( p < 0.001 ) . The amount of blood loss different significantly , with 336 ml and 483 ml respectively ( p < 0.001 ) . No significant difference was found in Apgar scores . No difference was found in overall postoperative complications , wound infection , febrile illness , febrile morbidity , wound dehiscence affected by the new technique . Significantly less suture material was used during Misgav-Ladach caesarean section compared to Pfannenstiel technique ( p < 0.001 ) . CONCLUSION The Misgav-Ladach method of caesarean section has advantages over the Pfannenstiel technique by being significantly quicker to perform , with the reduced amounts of bleeding and suture material . The women were satisfied with the appearance of their scars . In this study no negative effects of the new operation technique were discovered BACKGROUND The cesarean section was design ed to extract to the neoborn , when the childbirth becomes difficult by the natural routes . The institutional obstetrical work dem and s long surgical time and high raw material s ; therefore , simpler procedures must be implemented . OBJECTIVE To compare traditional cesarean section vs Misgav-Ladach technique to assess surgical time , and hospital stay and costs . PATIENTS AND METHODS Forty-eight pregnant patients at term with obstetrical indication for cesarean delivery were r and omized in two groups : 24 were su bmi tted to traditional cesarean and 24 to Misgav-Ladach technique . The outcomes included surgical time , bleeding , amount of sutures employed , pain intensity and some others adverse effects . RESULTS The surgical time with Misgav-Ladach technique was shorter compared with traditional cesarean section , bleeding was consistently lesser and pain was also low . None adverse effects were registered in both groups . CONCLUSION Although short follow-up showed significant operative time reduction and less bleeding , longer follow-up should be desirable in order to confirm no abdominal adhesions OBJECTIVE To compare the Pfannenstiel incision with transverse muscle‐cutting Maylard incision in women who had cesarean delivery . METHODS Patients were assigned r and omly to a Pfannenstiel or Maylard incision . Postoperative ttreatment was similar for each group . Surgical characteristics , complications , postoperative pain ( visual analog scale , analgesic use ) , and related quality of life ( 1‐ and 3‐month self‐administered question naires ) were analyzed . Abdominal wall muscle recovery was compared objective ly by dynamometer . RESULTS Fifty‐four women had a Pfannenstiel incision and 43 had the Maylard incision . There were no differences in intraoperative characteristics , postoperative morbidity , or pain . Women 's responses to the Nottingham Health Profile question naire at 1 and 3 months postoperatively and clinical and isokinetic testing for abdominal wall strength were similar between the two groups . CONCLUSION Transecting the rectus muscle was no more deleterious than the Pfannenstiel incision . There was no difference in objective ly measured abdominal wall strength Objective The purpose of this study was to determine whether the method used to exp and the uterine incision ( sharp vs. blunt ) for cesarean section ( CS ) affects maternal blood loss . Method A prospect i ve study conducted on 200 nulliparous who underwent lower segment transverse CS divided into two groups . One hundred women were assigned to have blunt expansion of the uterine incision by fingers of the surgeon , and 100 women to have sharp expansion using b and age scissors . Finally , a comparison of two groups was made regarding blood loss , change in hematocrit , uterine tears and blood transfusion . P < 0.05 was considered significant . Results Maternal blood loss and postoperative hematocrit drop were significantly higher in sharp group ( 375 ± 95 cm3 in blunt vs. 443 ± 86 in sharp , P = 0.001 and 2.4 ± 2.6 in blunt vs. 4.1 ± 2.6 in sharp , P = 0.001 , respectively ) . There was no significant difference in the extension of uterine incision . Conclusions Our findings support that blunt expansion of uterine incision during lower segment cesarean is safer and easier than sharp expansion OBJECTIVE Both blunt and sharp expansion of the initial incision at transverse cervical cesarean birth have advocates , on the basis of theoretic concerns . We sought to study the incidence of complications , including unintended extension , associated with each of these methods by comparison by means of a prospect i ve , r and omized study . STUDY DESIGN Women scheduled to undergo nonemergency cesarean birth were assigned to blunt and sharp expansion groups . Other than expansion of the incision , st and ard technique was used throughout surgery . Data , including length and number of unintended extensions , vessel laceration , and length of surgery , were recorded immediately . RESULTS The blunt ( n = 139 ) and sharp ( n = 147 ) expansion groups were similar with regard to indication and duration of labor . No difference in the incidence of unintended extension , postoperative endometritis , duration of surgery , or estimated blood loss was noted . The frequency of unintended extension ( 1.4 % , 15.5 % , and 35.0 % for no labor and first and second stages , respectively ) correlated with the stage of labor . CONCLUSION Blunt and sharp expansions of the uterine incision are equivalent in ease and safety OBJECTIVE The aim of the study was to evaluate the outcome of two different methods of cesarean section ( CS ) . DESIGN The study was design ed as a prospect i ve , r and omized , controlled trial . SETTING All CS were performed at the University Hospital in Uppsala , Sweden . POPULATION Fifty women admitted to hospital for a first elective CS were consecutively included in the study . They were r and omly allocated to two groups . METHODS One group was operated on by the Misgav Ladach method for CS and the other group by the Pfannenstiel method . All operations were performed by the same surgeon . MAIN OUTCOME MEASURES Duration of operation , amount of bleeding , analgesics required , scar appearance and length of hospitalization . RESULTS Operating time was significantly different between the two methods , with an average of 12.5 minutes with the Misgav Ladach method and 26 minutes with the Pfannenstiel method ( p<0.001 ) . The amount of blood loss differed significantly , with 448 ml and 608 ml respectively ( p=0.017 ) . Significantly less analgesic injections and tablets ( p=0.004 ) were needed after the Misgav Ladach method . CONCLUSION The Misgav Ladach method of CS has advantages over the Pfannenstiel method by being significantly quicker to perform , with a reduced amount of bleeding and diminished postoperative pain . The women were satisfied with the appearance of their scars . In this study no negative effects of the new operation technique were discovered AIM A common anatomical consequence of low-segment cesarean section is the presence of a pouch on the anterior uterine wall that can be detected by sonography or hysteroscopy . Different suturing techniques have been compared ( single vs double layer ) and showed no substantial differences . This prospect i ve longitudinal study was aim ed at evaluating the outcome of the cesarean scar , comparing two different types of single-layer sutures by transvaginal ultrasound and hysteroscopy . MATERIAL AND METHODS The study sample consisted of two groups of 30 singleton primiparae at term who delivered by elective low segment cesarean section . In the first group , uterine closure was done with locked continuous single-layer sutures and in the second group , with single-layer interrupted sutures . Patients were assessed by transvaginal ultrasound and hysteroscopy , between the 6th and the 12th month after delivery , and again at the 24th month . Ultrasound measurements were made of the pouch area , if present . RESULTS A bell-shaped uterine wall defect was seen at ultrasound in 36 ( 85.71 % ) of 42 patients who completed the follow up at the 24th month . It was larger in the group of patients with closure by continuous sutures ( 6.2 [ 2.1 - 14.7 ] mm2 ) as compared to interrupted sutures ( 4.6 [ 1.9 - 8.2 ] mm2 , P = 0.03 ) . Hysteroscopy confirmed the presence of the wall defect in all 36 cases , but different hysteroscopic outcomes were observed . CONCLUSION Locked continuous sutures seem to cause a larger defect as compared to interrupted sutures , probably due to a greater ischemic effect exerted on the uterine tissue To determine if blunt or sharp expansion of the uterus at caesarean delivery is associated with increased maternal peripartum haemorrhage as estimated by the drop in hematocrit . Prospect i ve r and omised intention to treat clinical trial of women undergoing elective or urgent caesarean delivery at at least 36 weeks gestation . Two study groups were formed ; after an initial hysterotomy which consisted in a transverse uterine incision of the lower segment , in the blunt group , the surgeon 's indexes exp and ed the initial incision bilaterally and cephalad ; in the sharp group , expansion of the initial incision was made using scissors . The primary outcome measure was the mean drop in hematocrit and p < 0.05 was considered significant . Three hundred women were r and omised : 153 to the sharp group and 147 to the blunt group . The demographic and clinical characteristics of the two population s were similar . There were no statistically significant differences between the groups in estimated blood loss as assessed by the mean drop in hematocrit ( % ) ( respectively 1.71 + /- 3.18 versus blunt group 1.91 + /- 3.28 p = 0.58 non significant ) . Our findings support that sharp or blunt expansion of hysterotomy during caesarean section equally affect blood loss as estimated by drop in hematocrit INTRODUCTION Caesarean delivery remains the most common intraperitoneal surgical procedure in obstetric and gynaecologic practice . Since time immemorial there have been countless efforts to improve the technique of caesarean section . One such innovative breakthrough technique is the Misgav Ladach method of caesarean of section . The objective of this trial was to compare the intraoperative and short-term postoperative outcomes between the conventional and the Misgav-Ladach technique for caesarean section . MATERIAL S AND METHOD The r and omized prospect i ve comparative study was carried out in the department of Obstetrics and Gynaecology , B.P Koirala Institute of Health Sciences , Dharan Nepal . Four hundred patients were r and omized to either Misgav Ladach or the Conventional method of caesarean section . Only term pregnancies with singleton foetuses ' were included whereas pregnancies with previous caesarean section were excluded from the study . The study period was from September 2001 to September 2004 . RESULT There was not much difference in the demographic variables between the two groups . The age of the patients ranged between 18 - 40 years . The mean age of patients in Misgav Ladach and conventional group was 24.5 and 23.6 years respectively . Foetal distress was the commonest indication for caesarean section followed by non progress of labour . The mean incision to delivery interval , operating time and blood loss in the Misgav Ladach group was 1 minute 30 seconds , 16 minutes and 35 0ml as compared to 3 minutes , 28 minutes and 600 ml in the conventional group respectively . 3.5%of patients in the Misgav Ladach group showed febrile morbidity as compared to 7 % in the conventional group . 19 % from conventional group and only 4%from Misgav Ladach group required added analgesia . Almost equal number of patients ( 10 - 12 ) in each group experienced significant headache.).0.1%in the Misgav group and 5 % in the Conventional group required post operative blood transfusion . Four patients from the conventional group had their wound gaped . The number of neonates requiring intensive care was sixteen ( 8 % ) in the conventional group and 3 ( 1.5 % ) in the Misgav group.6.5 % from conventional group and 2 % from Misgav Ladach group required maternal intensive care admissions . CONCLUSION Misgav-Ladach technique has been be associated with shorter operative time , quicker recovery , and lesser need for postoperative medications , when compared with traditional caesarean section . It has also been shown to be more cost-effective . A further advantage of the technique may be the shorter time taken for the delivery of the child Although stapling techniques have gained wide acceptance in general surgery , they are still not commonly used in obstetrics . U.S. Surgical Corporation has introduced a stapling device suitable for use in cesarean sections . The copolymer staples ( a blend of polylactic and polyglycolic acids ) maintain their tensile strength until healing occurs and absorb without producing granulation tissue . The benefits include minimal trauma to tissue and reduced operating time , blood loss and postoperative morbidity . From July 1988 to February 1989 , all patients undergoing low transverse cervical cesarean sections were r and omized to either group 1 with the uterine incision performed in a routine manner or group 2 with the uterine incision cut and stapled using the Stapler . The preoperative management , intraoperative technique and postoperative surveillance were similar for both groups . The uterine incision was assessed by pelvic sonography during the postpartum period . Statistical analysis was performed using Fisher 's exact test and chi-square analysis . Both groups were comparable for age , race , parity , gestational age and primary diagnosis . The length of the operative procedure was significantly shorter ( p less than 0.05 ) in the stapled group . These patients also had a statistically significantly decreased incidence of uterine incisions and lacerations . All other parameters were not significantly different in the two groups . The stapled uterine incisions were visible by ultrasonography in more patients in the stapled group throughout the postpartum period than in the sutured group . Thus , stapling of the uterine incision was an acceptable alternative to traditional suturing techniques and it was possible to visualize clearly these incisions during the postpartum period OBJECTIVE The purpose of this study was to compare 2 methods of expansion of the uterine incision at the time of cesarean delivery . STUDY DESIGN Women who underwent a low-segment transverse cesarean delivery were assigned r and omly to have the blunt expansion of the uterine incision by the physician separating the fingers either in a transversal direction or in a cephalad-caudad direction . The primary outcome measure was the incidence of unintended extensions . RESULTS The transversal ( n = 406 ) and cephalad-caudad ( n = 405 ) expansion groups were similar with regard to patient characteristics , indication to surgery , type of anesthesia , and proportion of emergency procedures . No difference in the need for transfusions ( 0.7 % vs 0.7 % ; P = 1.0 ) or estimated blood loss ( 440 + /- 341 vs 398 + /- 242 mL ; P = .09 ) was noted . The incidence of unintended extension ( 7.4 % vs 3.7 % ; P = .03 ) and blood loss of > 1500 mL ( 2.0 % vs 0.2 % ; P = .04 ) was significantly higher in the transversal expansion group , compared with the cephalad-caudad group . Transversal expansion was an independent contributor to unintended extension and blood loss of > 1500 mL. CONCLUSION Because it is associated with less risk of unintended extension and excessive blood loss , expansion of the uterine incision with a cephalad-caudad traction should be preferred to transversal expansion when a cesarean delivery is performed Objective To determine whether the method used to exp and the uterine incision for caesarean delivery affects the incidence of intra‐operative haemorrhage Objective To investigate whether a series of changes in the current caesarean section operative routine , based on new knowledge , would be beneficial Cesarean section ( CS ) is the commonest major operation carried out in many low income countries . A new technique for CS , called the Misgav Ladach procedure , was evaluated in a r and omized trial in Nazareth Hospital ( Kiambu District , Kenya ) . A total of 160 patients were assigned to the Misgav Ladach procedure ( n=80 ) or to the traditional CS as performed in most rural hospitals in low income countries ( n=80 ) . The two groups were analyzed by operating time , presence of infection and febrile morbidity , grade of postoperative pain , starting of fluid and solid alimentation , and development of incisional hernia and hypertrophic scar . The operating time of the Misgav Ladach procedure was significantly shorter . 20.4 ( SD 6.1 ) minutes versus 30.4 ( SD 6.1 ) minutes ( p < 0.001 ) . A total of 5 wound infections ( 6.2 % ) were seen with the Misgav Ladach procedure versus 16 ( 20.0 % ) in the control group ( p=0.01 ) . The number of analgesic doses required during the postoperative period were significantly less in the Misgav Ladach group : 1.3 ( SD 0.6 ) versus 1.9 ( SD 0.7 ) ampuls of pethidine ( p<0.001 ) and 15.1 ( SD 2.0 ) versus 16.4 ( SD 1.8 ) tablets of ibuprofen ( p<0.001 ) . Incisional pain was significantly less in the Misgav Ladach group : Visual Analogue Scale score 3.0 ( SD 1.5 ) versus 4.9 ( SD 2.0),p<0.01 . The patients in the Misgav Ladach group began drinking fluids voluntarily [ 19.1 ( SD 4.5 ) hours versus 20.6 ( SD 4.0 ) hours;p=0.01 ] and eating solid food [ 41.2 ( SD 9.3 ) hours versus 46.1 ( SD 9.0 ) hours;p<0.01 ] significantly before than those in the control group . At the 6-week follow-up , the presence of hypertrophic scar was significantly associated with the traditional procedure ( 2.1 % vs. 48.8%;p<0.001 ) . We conclude that the Misgav Ladach operation should become the st and ard method for performing CS in low income countries , particularly in rural hospitals . RésuméLa césarienne ( CS ) est l’intervention majeure la plus fréquemment réalisée dans beaucoup de paysà basse économie . Pour évaluer une nouvelle technique de césarienne , appelé le procédé de « Misgav Ladach » , dans une étude r and omiséeà l’hôpital Nazareth Hospital ( Kiambu District , Kenya ) , 160 patientes ont été allouées soit au procédé de « Misgav Ladach » ( n=80 ) soità la césarienne traditionnelle CS ( n=80 ) , comme réalisée dans la plus gr and e majorité des hôpitaux ruraux dans les paysà revenu peu élevé . On a analysé la durée de l’opération , la présence d’infection et la morbidité hyperthermique , le degré de la douleur postopératoire , le début de l’alimentation liquidienne et solide , le développement d’une éventration , et la survenue d’une cicatrice hypertrophique . La durée opératoire pour le procédé de « Misgav Ladach » a été significativement plus courte ( 20.4 ( SD=6.1 ) versus 30.4 ( SD=6.1 ) minutes ( p<0.001 ) ) . On a noté cinq cas d’infection pariétale ( 6,2 % ) dans la technique de Misgav Ladach comparésà 16 cas ( 20.0 % ) dans le groupe contrôle ( p=0.01 ) . Les patientes dans le groupe Misgav Ladach ont eu besoin de moins de doses d’analgésiques dans la période postopératoire : 1.3 ( SD=0.6 ) versus 1.9 ( SD=0.7 ) ampoules de Péthidine ( p<0.001 ) et 15.1 ( SD=2.0 ) versus 16.4 ( SD=1.8 ) compresses d’ibuprofène ( p<0.001 ) . La douleur au niveau de la cicatrice était significativement moindre dans le groupe « Misgav Ladach » avec un scoreà l’échelle visuelle analogue de 3,0 ( SD=1.5 ) versus 4,9 ( SD=2.0 ) , p<0.01 . De plus , les patients dans le groupe « Misgav Ladach » ont commencéà boire des liquides ( 19.1 , SD=4.5 , versus 20.6 , SD=4.0 heures , p=0.01 ) et a mangé des aliments solides ( 41.2 , SD=9.3 , versus 46.1 , SD=9.0 heures , p<0.01 ) plus tôt que celles du group de contrôle . A six semaines , il y avait plus de femmes qui avaient une cicatrice hypertrophique dans le groupe de césarienne classique ( 2.1 % versus 48.8 % , p<0.001 ) . Nous concluons que le procédé de « Misgav Ladach » devrait être la méthode de référence pour césarienne dans les paysà revenue bas , surtout dans les hôpitaux ruraux . ResumenLa operación de cesárea ( CS ) es la intervención más frecuente en paises subdesarrollados . Con objeto evaluar una nueva técnica de CS , denominada Misgaw Ladach , se efectuó un estudio r and omizado en el Hospital de Nazareth ( distrito de Kiambu , Kenya ) . Se recopilaron 160 pacientes en las que se realizó la técnica de Misgaw Ladach ( n=80 ) o la CS convencional , como se realiza en la mayoria de los hospitales rurales en los paises en vias de desarrollo ( n=80 ) . Ambos grupos se analizaron para valorar el tiempo operatorio , la infección y la morbilidad febril , el grado de dolor postoperatorio , el momento en que se comenzó la ingesta liquida y sólida , el desarrollo de eventraciones y de cicatrización queloidea . El tiempo operatorio con la técnica de Misgaw Ladach es significativamente más cortö 20.4 ( SD=6.1 ) vs 30.4 ( SD=6.1 ) minutos ( p<0.001 ) . Con la técnica de Misgaw Ladach se observaron 5 infecciones de la herida operatoria ( 6.2 % ) frente a 16 ( 20 % ) en el grupo control ( p=0.01 ) . El número de dosis analgésicas requeridas por las operadas con la técnica de Misgaw Ladach fue significativamente menor : 1.3 ( SD=0.6 ) vs 1.9 ( SD=0.7 ) ampollas de petidina ( p<0.001 ) y 15.1 ( SD=2.0 ) vs 16.4 ( SD=1.8 ) apósitos de Ibuprofen ( p<0.001 ) . El dolor de la herida operatoria fue significativamente menor con la técnica de Misgaw Ladach : En la escala analógica visual alcanzó un grado de 3.0 ( SD=1.5 ) vs 4.9 ( SD=2.0 ) , ( p<0.01 ) . Además , las pacientes operadas con la técnica de Misgaw Ladach empezaron voluntariamente a beber ( 19.1 , SD=4.5 vs 20.6 SD=4.0 horas , p=0.01 ) y a ingerir alimentos sólidos ( 41.2 SD=9.3 vs 46.1 SD=9.0 horas , p<0.01 ) , mucho antes que las del grupo control . Tras un seguimiento de 6 semanas se observaron cicatrices queloideas en el 2.1 % de las intervenciones realizadas con la técnica de Misgaw Ladach frente a un 48.8 % de las operadas de cesárea con la técnica tradicional ( p<0.001 ) . Concluimos senãl and o que la técnica de Misgaw Ladach CS debe convertirse en el método estándar para la realización de una cesárea en pueblos económicamente débiles y , especialmente en los hospitales rurales Blood loss during Caesarean section is mainly due to the hysterotomy . A new technique to reduce this blood loss has been evaluated in a prospect i ve controlled clinical trial in 89 patients . The operation technique was st and ardized according to Joel-Cohen . In the control group ( n = 45 ) the low transversal incision was enlarged by scissors in an upward swing , in the staple group ( n = 44 ) the incision was enlarged by introducing the poly CS 57 instrument with absorbable staples . A double row of staples sealed blood vessels and secured the three uterine layers just before the instrument 's blade cut the uterine wall . The two groups were comparable as to the indications for the CS , first or repeat CS , primary or secondary CS , maternal age and parity . The duration of the operation , postoperative complications and hospital stay was equal . However , the blood loss in the ' staple ' group was significantly less than in the control group . The conclusions are that this new technique reduced blood loss during Caesarean section , and moreover , it appeared to be extremely useful in patients with varicose veins in the lower uterine segment or placenta praevia This r and omized controlled trial compares the use of the Auto Suture Poly CS 57 disposable surgical stapler ( n = 98 ) with st and ard hysterectomy ( n = 102 ) in low transverse cesarean sections . Subjective assessment of blood loss by the surgeon result ed in lower mean ( + /- SEM ) total blood loss estimates in the stapled group ( 492 + /- 24 ml ) than in the nonstapled group ( 579 + /- 38 ml ) ( p = 0.05 ) . However , surgeon 's estimation of blood loss as a result of the hysterotomy and blood loss estimated by the hemoglobin deficit measured on the second postoperative day did not significantly differ between the two groups . The use of the stapling device tended to lengthen the total operating time , which averaged 42.5 minutes in the group with the staples and 39.2 minutes in the group with the st and ard hysterotomy ( p = 0.05 ) . The risk of febrile morbidity , the frequency of endometritis , and the length of hospitalization were similar in the two groups . Our results do not support the routine use of the Auto Suture Poly CS 57 disposable surgical stapler in low transverse cesarean sections OBJECTIVE To compare an innovative cesarean section based on Joel-Cohen incision with the traditional Pfannenstiel technique in terms of operative data and post-operative recovery . METHOD Out of 158 r and omized patients , 83 patients underwent the innovative cesarean section ( Joel-Cohen incision , one-layer locked uterine suture , no peritoneization ) and 75 the traditional operative approach ( Pfannenstiel incision , double layer closure of the uterus , visceral and parietal peritoneization ) . Operative data and post-operative morbidity were compared ; sample size was calculated to detect a 13 % difference in the occurrence of post-operative fever with a statistical power of 80 % . RESULT Post-operative fever was not different in the two groups . Total operating time was shorter with the innovative technique : 31.6 + /-1.38 min vs. 44.4+/-1.44 ( P=0.0001 ) and fewer sutures were used : 3.6+/-0.13 vs. 6+/-0.13 ( P=0.001 ) . Patients operated by the new technique began moving sooner and intestinal function restarted earlier . CONCLUSION The proposed technique made for shorter operating times and faster recovery but no decrease in puerperal morbidity OBJECTIVE : To survey the uterine scar thickness by ultrasonography in women r and omly assigned to one- or two-layer hysterotomy closure after primary cesarean delivery . METHODS : This was a r and omized , blinded trial of uterine scar closure with ultrasonographic follow-up . Thirty consecutive patients undergoing primary cesarean delivery were enrolled and r and omly assigned to one- or two-layer closure of the hysterotomy . Ultrasound surveillance of the uterine scar thickness was performed at baseline ( before surgery ) and 48 hours , 2 weeks , and 6 weeks post partum . RESULTS : Patient compliance with the postpartum surveillance protocol was 90 % , and the uterine scar was visualized in 99 % of attempted ultrasonographic examinations . There were no differences between groups at baseline or at any of the follow-up evaluations . An initial 5- to 6-fold increase in uterine scar thickness was observed , followed by a gradual decrease with the 6-week measurements still thicker than baseline . Repeated measures analysis of variance showed significant variation across time points starting either at baseline ( P<.001 ) or at 48 hour postoperatively ( P<.001 ) , but this variation did not depend on closure type ( P=.79 for all visits and P=.81 beginning with 48-hour postoperative time point ) . CONCLUSION : The process of uterine scar remodeling can be successfully monitored by ultrasonography . Uterine scar thickness diminishes progressively after both one- or two-layer closure but does not vary with mode of hysterotomy closure . The uterine scar thickness remains increased even at 6 weeks post partum , suggesting that the process of uterine scar remodeling extends beyond the traditional postpartum period . CLINCAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00224250 LEVEL OF EVIDENCE : Objective To determine whether a low transverse cesarean closure method in one or two layers affects subsequent pregnancy outcome . Methods In a prospect i ve trial reported previously , 906 women were assigned r and omly to either one- or two-layer uterine closure . One hundred sixty-four women had a subsequent pregnancy and delivery ( 18 weeks ' gestation or longer ) at our institution . Maternal and neonatal outcomes were ascertained by medical chart review and compared between the one- and two-layer closure groups . Results Of the 164 subsequent deliveries , 83 had previous closure in one layer , whereas 81 had involved a two-layer closure . The demographic characteristics of these two groups were similar . Nineteen women ( 12 % ) underwent elective repeat cesareans without labor , and the remaining 145 experienced labor . Length of labor , mode of delivery , duration of hospital stay , gestation at delivery , and the incidences of uterine scar dehiscence , chorioamnionitis , postpartum metritis , hemorrhage , transfusion , and abnormal placentation did not differ significantly between the groups . Selected neonatal outcomes , including Apgar scores , cord pH , birth weight , and perinatal death , were similar between groups as well . Conclusions These findings suggest that the type of low transverse cesarean closure does not significantly affect the outcome of the next pregnancy OBJECTIVE Closure of a low transverse cesarean incision with one layer of suture results in less operating time , better hemostasis , and less infectious morbidity than a two-layer closure . STUDY DESIGN At our institution 906 women were r and omized to closure of a low transverse cesarean incision with either one continuous layer of a locking No. 1 chromic suture and a CTX needle ( n = 457 ) or two continuous layers of No. 1 chromic suture with the first layer locked ( n = 449 ) . The Student t test , chi 2 test of proportion , and Wilcoxon rank sum test were used to compare groups of patients . RESULTS A one-layer closure required less operative time , 43.8 versus 47.5 minutes ( p = 0.0003 ) . Fewer additional uterine hemostatic sutures were required in 369 women in whom either the one- ( n = 179 ) or the two-layer ( n = 190 ) closure did not achieve hemostasis ( p = 0.046 ) . Endometritis was similar in both groups , 83 ( 22 % ) in the one-layer group versus 65 ( 18 % ) in the two-layer group ( p = 0.17 ) . In no outcome assessment was the two-layer closure superior to the one-layer closure . CONCLUSION We recommend a one-layer closure when its use is anatomically feasible PURPOSE OF INVESTIGATION To compare advantages and disadvantages of exteriorized and in situ repair techniques of uterine incision during cesarean section . METHODS A total of 338 patients delivered by cesarean section were included in the study . Patients were r and omized according to the location of uterine incision repair ; the uterus was exteriorized ( n = 171 ) or not ( in situ repair group ) ( n = 167 ) during cesarean section . Two groups were compared in terms of blood loss , operation time , temperature patterns , analgesic dosage , length of hospital stay , incidence of nausea and vomiting . RESULTS There was no significant difference in postoperative analgesic dosage , temperature patterns , drops in hemoglobin or hematocrit levels and in the incidence of postoperative nausea and vomiting between the two groups . Operation time and length of hospital stay were significantly shorter in the in situ repair group , when it was compared to those of which the uterus was exteriorized ( 30.64 + /- 8.65 vs 33.02 + /- 9.54 min . , p = 0.011 and 2.23 + /- 0.49 vs 2.45 + /- 0.94 days , p = 0.045 ) . CONCLUSIONS Exteriorized and in situ repair of uterine incisions have similar effects on blood loss , temperature patterns , postoperative analgesic dosage and the incidence of postoperative nausea and vomiting . Although both methods of uterine incision repair are valid options during surgery , cesarean sections took less time and length of hospital stay was shorter when uterine incision was repaired in situ The objective of this study was to examine the feasibility of a modified technique of cesarean section in which the uterine incision is sutured in one layer and the visceral and parietal peritoneum are left open . Two hundred patients undergoing a low segment cesarean section were prospect ively r and omized ( according to the patients ' identity numbers ) into two groups . The first group had st and ard cesarean section including a continuous double layer closure of uterine incision in addition to closure of visceral and parietal peritoneum . The second group underwent the modified procedure as described above . The modified technique compared to the st and ard technique , result ed in shorter operative time ( 32 + /- 11 versus 44 + /- 16 min , P < 0.0001 ) and a reduced need for postoperative sedation ( P < 0.004 ) . The operative procedure was shown , by multiple regression analysis , to be the significant factor that determined its length . Postoperative morbidity was similar in the two groups . The modified technique of cesarean section reduces operative time and postoperative narcotic requirement , and has no adverse affect on postoperative recovery . A double-layer closure of low uterine incision , re-approximation of bladder flap , and closure of parietal peritoneum , as in the st and ard technique , do not seem to be essential steps of cesarean section . Larger studies are needed to ensure the safety of one-layer uterine closure in future deliveries BACKGROUND In order to minimize intra operative blood loss during caesarean section , two techniques of expansion of uterine incision ( sharp versus blunt ) while performing lower segment transverse caesareans deliveries and their effect upon intraoperative blood loss were studied . Moreover , each method was also compared for its inadvertent extension of uterine incision laterally or into the broad ligament , into the cervix or vagina . METHOD A quasi-experimental study with convenient sampling , involving two groups of women who underwent lower transverse segment Cesarean section . Both groups were studied for their demographic characteristics and clinical data . St and ard surgical techniques were used in both groups except the expansion of uterine incision , either by sharp or blunt methods . Finally a comparison of two groups was made regarding blood loss , change in haematocrit , blood transfusion and uterine tears . The study was conducted at Combined Military Hospital Rawalpindi during May 2002 to April 2003 . RESULTS No significant difference was found between the two groups regarding their demographic characteristics and clinical data . Intraoperative blood loss and post-operative hematocrit drop were more significant in the patient group in which a blunt uterine incision was made . Besides , more patients in this group received blood transfusions . Unintended extension of uterine ( tears ) was also significantly higher in this group . CONCLUSION Sharp expansion of uterine incision during low segment caesarean section is safer and precise based on these results Objective To determine whether the Misgav Ladach caesarean section technique can offer benefits compared with conventional caesarean section technique in the prevailing conditions of a busy African tertiary centre OBJECTIVE To compare the rates of intraoperative and postoperative complications of uterine repair when performed in situ or extra-abdominally following cesarean delivery . METHODS In this prospect i ve r and omized study 4925 women who underwent cesarean delivery were r and omly assigned to in situ ( n = 2462 ) or extra-abdominal ( n = 2463 ) uterine repair ( group 1 and group 2 , respectively ) . The study compares drop in hemoglobin concentration ( as a measure of intraoperative blood loss ) . It also compares operating time , time to return of bowel sound , and duration of hospitalization as well as rates of uterine atony , blood transfusion , intraoperative complications , additional use postoperative analgesics , endometritis , and wound infection . RESULTS Uterine atony developed in 96 women ( 3.8 % ) in group 1 and 226 women ( 9.1 % ) in group 2 ( P = 0.001 ) . Moreover , the operating time and the time to return of bowel sound were shorter and the rates of both additional use of postoperative analgesics and wound infection were lower in group 1 ( P = 0.001 , P = 0.002 , P = 0.001 , and P = 0.003 , respectively ) . CONCLUSION Fewer cases of uterine atony , a shorter operating time , a faster return of bowel function , a lesser need for postoperative analgesics , and lower rates of additional use of postoperative analgesics and wound infections suggest that in-situ uterine repair ought to be preferred to extra-abdominal uterine repair following cesarean delivery |
12,131 | 27,362,526 | Adherence was higher for technology-based interventions than traditional interventions independent of study site , level of supervision , and delivery mode .
Discussion : This systematic review provides evidence that technology offers a well-accepted method to provide older adults with engaging exercise opportunities , and adherence rates remain high in both supervised and unsupervised setting s at least throughout the first 12 weeks of intervention .
The higher adherence rates to technology-based interventions can be largely explained by the high reported levels of enjoyment when using these programs .
However , the small sample sizes , short follow-up periods , inclusion of mostly healthy older people , and problems related to the methods used to report exercise adherence limit the generalizability of our findings .
Conclusion : This systematic review indicates that technology-based exercise interventions have good adherence and may provide a sustainable means of promoting physical activity and preventing falls in older people . | Background and Purpose : Exercise participation and adherence in older people is often low .
The integration of technology-based exercise programs may have a positive effect on adherence as they can overcome perceived barriers to exercise .
Previous systematic review s have shown preliminary evidence that technology-based exercise programs can improve physical functioning .
However , there is currently no in-depth description and discussion of the potential this technology offers to improve exercise adherence in older people .
This review examines the literature regarding older adults ' acceptability and adherence to technology-based exercise interventions . | Background Stepping impairments are associated with physical and cognitive decline in older adults and increased fall risk . Exercise interventions can reduce fall risk , but adherence is often low . A new exergame involving step training may provide an enjoyable exercise alternative for preventing falls in older people . Purpose To assess the feasibility and safety of unsupervised , home-based step pad training and determine the effectiveness of this intervention on stepping performance and associated fall risk in older people . Design Single-blinded two-arm r and omized controlled trial comparing step pad training with control ( no-intervention ) . Setting / Participants Thirty-seven older adults residing in independent-living units of a retirement village in Sydney , Australia . Intervention Intervention group ( IG ) participants were provided with a computerized step pad system connected to their TVs and played a step game as often as they liked ( with a recommended dose of 2–3 sessions per week for 15–20 minutes each ) for eight weeks . In addition , IG participants were asked to complete a choice stepping reaction time ( CSRT ) task once each week . Main Outcome Measures CSRT , the Physiological Profile Assessment ( PPA ) , neuropsychological and functional mobility measures were assessed at baseline and eight week follow-up . Results Thirty-two participants completed the study ( 86.5 % ) . IG participants played a median 2.75 sessions/week and no adverse events were reported . Compared to the control group , the IG significantly improved their CSRT ( F31,1 = 18.203 , p<.001 ) , PPA composite scores ( F31,1 = 12.706 , p = 0.001 ) , as well as the postural sway ( F31,1 = 4.226 , p = 0.049 ) and contrast sensitivity ( F31,1 = 4.415 , p = 0.044 ) PPA sub-component scores . In addition , the IG improved significantly in their dual-task ability as assessed by a timed up and go test/verbal fluency task ( F31,1 = 4.226 , p = 0.049 ) . Conclusions Step pad training can be safely undertaken at home to improve physical and cognitive parameters of fall risk in older people without major cognitive and physical impairments . Trial Registration Australian New Zeal and Clinical Trials Registry ACTRN12611001081909 Purpose Interactive cognitive-motor training ( ICMT ) requires individuals to perform both gross motor movements and complex information processing . This study investigated the effectiveness of ICMT on cognitive functions associated with falls in older adults . Methods A single-blinded r and omized controlled trial was conducted in community-dwelling older adults ( N = 90 , mean age 81.5±7 ) without major cognitive impairment . Participants in the intervention group ( IG ) played four stepping games that required them to divide attention , inhibit irrelevant stimuli , switch between tasks , rotate objects and make rapid decisions . The recommended minimum dose was three 20-minute sessions per week over a period of 16 weeks unsupervised at home . Participants in the control group ( CG ) received an evidence -based brochure on fall prevention . Measures of processing speed , attention/executive function ( EF ) , visuo-spatial ability , concerns about falling and depression were assessed before and after the intervention . Results Eighty-one participants ( 90 % ) attended re- assessment . There were no improvements with respect to the Stroop Stepping Test ( primary outcome ) in the intervention group . Compared to the CG , the IG improved significantly in measures of processing speed , visuo-spatial ability and concern about falling . Significant interactions were observed for measures of EF and divided attention , indicating group differences varied for different levels of the covariate with larger improvements in IG participants with poorer baseline performance . The interaction for depression showed no change for the IG but an increase in the CG for those with low depressive symptoms at baseline . Additionally , low and high-adherer groups differed in their baseline performance and responded differently to the intervention . Compared to high adherers , low adherers improved more in processing speed and visual scanning while high-adherers improved more in tasks related to EF . Conclusions This study shows that unsupervised stepping ICMT led to improvements in specific cognitive functions associated with falls in older people . Low adherers improved in less complex functions while high-adherers improved in EF . Trial Registration Australian New Zeal and Clinical Trials Registry Background Reaction time , coordination , and cognition performance typically diminish in older adults , which may lead to gait impairments , falls , and injuries . Regular strength – balance exercises are highly recommended to reduce this problem and to improve health , well-being , and independence in old age . However , many older people face a lack of motivation in addition to other strong barriers to exercise . We developed ActiveLifestyle , an information technology (IT)-based system for active and healthy aging aim ing at improving balance and strength . ActiveLifestyle is a training app that runs on a tablet and assists , monitors , and motivates older people to follow personalized training plans autonomously at home . Objective The objectives were to ( 1 ) investigate which IT-mediated motivation strategies increase adherence to physical exercise training plans in older people , ( 2 ) assess the impact of ActiveLifestyle on physical activity behavior change , and ( 3 ) demonstrate the effectiveness of the ActiveLifestyle training to improve gait speed . Methods A total of 44 older adults followed personalized , 12-week strength and balance training plans . All participants performed the exercises autonomously at home . Question naires were used to assess the technological familiarity and stage of behavior change , as well as the effectiveness of the motivation instruments adopted by ActiveLifestyle . Adherence to the exercise plan was evaluated using performance data collected by the app and through information given by the participants during the study . Pretests and posttests were performed to evaluate gait speed of the participants before and after the study . Results Participants were 75 years ( SD 6 ) , predominantly female ( 64 % ) , held a trade or professional diploma ( 54 % ) , and their past profession was in a sitting position ( 43 % ) . Of the 44 participants who enrolled , 33 ( 75 % ) completed the study . The app proved to assist and motivate independently living and healthy older adults to autonomously perform strength – balance exercises ( median 6 on a 7-point Likert scale ) . Social motivation strategies proved more effective than individual strategies to stimulate the participants to comply with the training plan , as well as to change their behavior permanently toward a more physically active lifestyle . The exercises were effective to improve preferred and fast gait speed . Conclusions ActiveLifestyle assisted and motivated independently living and healthy older people to autonomously perform strength – balance exercises over 12 weeks and had low dropout rates . The social motivation strategies were more effective to stimulate the participants to comply with the training plan and remain on the intervention . The adoption of assistive technology devices for physical intervention tends to motivate and retain older people exercising for longer periods of time Background Computer-based interventions have demonstrated consistent positive effects on various physical abilities in older adults . This study aims to compare two training groups that achieve similar amounts of strength and balance exercise where one group receives an intervention that includes additional dance video gaming . The aim is to investigate the different effects of the training programs on physical and psychological parameters in older adults . Methods Thirty-one participants ( mean age ± SD : 86.2 ± 4.6 years ) , residents of two Swiss hostels for the aged , were r and omly assigned to either the dance group ( n = 15 ) or the control group ( n = 16 ) . The dance group absolved a twelve-week cognitive-motor exercise program twice weekly that comprised progressive strength and balance training supplemented with additional dance video gaming . The control group performed only the strength and balance exercises during this period . Outcome measures were foot placement accuracy , gait performance under single and dual task conditions , and falls efficacy . Results After the intervention between-group comparison revealed significant differences for gait velocity ( U = 26 , P = .041 , r = .45 ) and for single support time ( U = 24 , P = .029 , r = .48 ) during the fast walking dual task condition in favor of the dance group . No significant between-group differences were observed either in the foot placement accuracy test or in falls efficacy . Conclusions There was a significant interaction in favor of the dance video game group for improvements in step time . Significant improved fast walking performance under dual task conditions ( velocity , double support time , step length ) was observed for the dance video game group only . These findings suggest that in older adults a cognitive-motor intervention may result in more improved gait under dual task conditions in comparison to a traditional strength and balance exercise program . Trial registration This trial has been registered under IS RCT N05350123 ( http://www.controlled-trials.com OBJECTIVE This study investigated the effect of playing Nintendo ( ® ) " Wii Fit ™ Plus " ( Nintendo of America , Inc. , Redmond , WA ) on body balance and physical activity of nursing home residents . SUBJECTS AND METHODS In a nonr and omized controlled trial within a nursing home , two intervention groups ( both n=8 ) were exposed to the same treatment and compared with a control group ( n=13 ) . Intervention Group 1 consisted of elderly individuals with regular Nintendo " Wii Fit " experience for at least 1 year . Elderly persons who were novices to the Nintendo " Wii Fit ( Plus ) " participated in intervention Group 2 . Control participants had no experience with the Nintendo " Wii Fit ( Plus ) " and did not participate in the Nintendo " Wii Fit Plus " sessions . Outcome measurements were taken at baseline and after the intervention , using the Berg Balance Scale and the LASA Physical Activity Question naire . Participants of both intervention groups played the Nintendo " Wii Fit Plus " for 10 minutes twice a week during 12 weeks . RESULTS Although balance improved for all three groups , there was no effect of playing " Wii Fit Plus " ( P=0.89 ) . On physical activity , the intervention did have a positive effect ( P=0.005 ) ; physical activity levels increased with a median of 54.3 ( interquartile range , 63.1 ) minutes/day for intervention Group 1 and a median of 60.7 ( interquartile range , 56.8 ) minutes/day for intervention Group 2 . CONCLUSIONS This study showed an effect of Nintendo " Wii Fit Plus " gaming on physical activity of nursing home residents , but not on their balance . The effect of physical activity should be consoli date d in a r and omized controlled trial in a broader population Abstract Background Falls and fall-related injuries are a serious public health issue . Exercise programs can effectively reduce fall risk in older people . The iStoppFalls project developed an Information and Communication Technology-based system to deliver an unsupervised exercise program in older people ’s homes . The primary aims of the iStoppFalls r and omized controlled trial were to assess the feasibility ( exercise adherence , acceptability and safety ) of the intervention program and its effectiveness on common fall risk factors . Methods A total of 153 community-dwelling people aged 65 + years took part in this international , multicentre , r and omized controlled trial . Intervention group participants conducted the exercise program for 16 weeks , with a recommended duration of 120 min/week for balance exergames and 60 min/week for strength exercises . All intervention and control participants received educational material including advice on a healthy lifestyle and fall prevention . Assessment s included physical and cognitive tests , and question naires for health , fear of falling , number of falls , quality of life and psychosocial outcomes . Results The median total exercise duration was 11.7 h ( IQR = 22.0 ) over the 16-week intervention period . There were no adverse events . Physiological fall risk ( Physiological Profile Assessment , PPA ) reduced significantly more in the intervention group compared to the control group ( F1,127 = 4.54 , p = 0.035 ) . There was a significant three-way interaction for fall risk assessed by the PPA between the high-adherence ( > 90 min/week ; n = 18 , 25.4 % ) , low-adherence ( < 90 min/week ; n = 53 , 74.6 % ) and control group ( F2,125 = 3.12 , n = 75 , p = 0.044 ) . Post hoc analysis revealed a significantly larger effect in favour of the high-adherence group compared to the control group for fall risk ( p = 0.031 ) , postural sway ( p = 0.046 ) , stepping reaction time ( p = 0.041 ) , executive functioning ( p = 0.044 ) , and quality of life ( p for trend = 0.052 ) . Conclusions The iStoppFalls exercise program reduced physiological fall risk in the study sample . Additional subgroup analyses revealed that intervention participants with better adherence also improved in postural sway , stepping reaction , and executive function . Trial registration Australian New Zeal and Clinical Trials Registry Trial ID : ACTRN12614000096651 International St and ard R and omised Controlled Trial Number : IS RCT Background This r and omized controlled pilot study aim ed to explore whether a cognitive-motor exercise program that combines traditional physical exercise with dance video gaming can improve the voluntary stepping responses of older adults under attention dem and ing dual task conditions . Methods Elderly subjects received twice weekly cognitive-motor exercise that included progressive strength and balance training supplemented by dance video gaming for 12 weeks ( intervention group ) . The control group received no specific intervention . Voluntary step execution under single and dual task conditions was recorded at baseline and post intervention ( Week 12 ) . Results After intervention between-group comparison revealed significant differences for initiation time of forward steps under dual task conditions ( U = 9 , P = 0.034 , r = 0.55 ) and backward steps under dual task conditions ( U = 10 , P = 0.045 , r = 0.52 ) in favor of the intervention group , showing altered stepping levels in the intervention group compared to the control group . Conclusion A cognitive-motor intervention based on strength and balance exercises with additional dance video gaming is able to improve voluntary step execution under both single and dual task conditions in older adults Poor balance is considered a challenging risk factor for falls in older adults . Therefore , innovative interventions for balance improvement in this population are greatly needed . The aim of this study was to evaluate the effect of a new virtual-reality system ( the Balance Rehabilitation Unit [ BRU ] ) on balance , falls , and fear of falling in a population of community-dwelling older subjects with a known history of falls . In this study , 60 community-dwelling older subjects were recruited after being diagnosed with poor balance at the Falls and Fractures Clinic , Nepean Hospital ( Penrith , NSW , Australia ) . Subjects were r and omly assigned to either the BRU-training or control groups . Both groups received the usual falls prevention care . The BRU-training group attended balance training ( two sessions/week for 6 weeks ) using an established protocol . Change in balance parameters was assessed in the BRU-training group at the end of their 6-week training program . Both groups were assessed 9 months after their initial assessment ( month 0 ) . Adherence to the BRU-training program was 97 % . Balance parameters were significantly improved in the BRU-training group ( P < 0.01 ) . This effect was also associated with a significant reduction in falls and lower levels of fear of falling ( P < 0.01 ) . Some components of balance that were improved by BRU training showed a decline after 9 months post-training . In conclusion , BRU training is an effective and well-accepted intervention to improve balance , increase confidence , and prevent falls in the elderly Background and purpose Numerous interventions have been proposed to improve balance in older adults with varying degrees of success . A novel approach may be to use an off-the-shelf video game system utilizing real-time force feedback to train older adults . The purpose of this study is to investigate the feasibility of using Nintendo ’s Wii Fit for training to improve clinical measures of balance in older adults and to retain the improvements after a period of time . Methods Twelve healthy older adults ( aged > 70 years ) were r and omly divided into two groups . The experimental group completed training using Nintendo ’s Wii Fit game three times a week for 3 weeks while the control group continued with normal activities . Four clinical measures of balance were assessed before training , 1 week after training , and 1 month after training : Berg Balance Scale ( BBS ) , Fullerton Advanced Balance ( FAB ) scale , Functional Reach ( FR ) , and Timed Up and Go ( TUG ) . Friedman two-way analysis of variance by ranks was conducted on the control and experimental group to determine if training using the Wii Balance Board with Wii Fit had an influence on clinical measures of balance . Results Nine older adults completed the study ( experimental group n = 4 , control group n = 5 ) . The experimental group significantly increased their BBS after training while the control group did not . There was no significant change for either group with FAB , FR , and TUG . Conclusion Balance training with Nintendo ’s Wii Fit may be a novel way for older adults to improve balance as measured by the BBS Clinicians are increasingly using evidence from high- quality clinical research to guide clinical decision making . Recent articles in this journal have examined research evidence to assist in clinical decisions as diverse as the prescription of running shoes,1 exercise therapy in the treatment of chronic disease2 and the use of protective equipment to prevent concussion.3 The most valid information about the effectiveness of healthcare interventions is provided by r and omised controlled trials and systematic review s of r and omised controlled trials.4 The Physiotherapy Evidence Data base ( PEDro ; http://www.pedro.org.au ) provides easy access to r and omised controlled trials and systematic review s of physiotherapy interventions . PEDro also includes links to evidence -based clinical practice guidelines . October 2009 marked the 10th anniversary of the launch of PEDro . PEDro is freely available on the internet . The data base indexes citation details , author abstract s and , where available , links to full text for r and omised controlled trials , systematic review s and practice guidelines in physiotherapy . Although the PEDro data base is design ed primarily for health professionals , a subsite , called Physiotherapy Choices ( http://www.physiotherapychoices.org.au ) , provides information in lay terms directly to consumers of physiotherapy services . As of August 2009 , more than 15 000 records ( 12 408 trials , 2060 review s and 603 guidelines ) have been indexed on PEDro . Each record is coded according to the subdiscipline(s ) of physiotherapy it addresses . PEDro now includes 615 r and omised controlled trials and 102 Objective : To compare the effectiveness of three protocol s ( Adapted Physical Activities , Wii Fit ® , Adapted Physical Activities + Wii Fit ® ) on the balance of independent senior subjects . Design : Case comparison study . Setting s : Healthy elderly subjects living in independent community dwellings . Subjects : Thirty-six subjects , average age 75.09 ± 10.26 years , took part in this study , and were r and omly assigned to one of the four experimental groups : G1 followed an Adapted Physical Activities training programme , while the second group ( G2 ) participated in Wii Fit ® training and the third one ( G3 ) combined both methods . There was no training for the fourth group ( G4 ) . All subjects trained once a week ( 1 hour ) for 20 weeks and were assessed before and after treatment . Main measures : The Tinetti test , unipedal tests and the Wii Fit ® tests . Results : After training , the scores in the Tinetti test decreased significantly ( P < 0.05 ) for G1 , G2 and G3 respectively in static conditions and for G1 and G3 in dynamic conditions . After training , the performance in the unipedal tests decreased significantly ( P < 0.05 ) for G1 and G3 . The position of the centre of gravity was modified significantly ( P < 0.05 ) for G2 and G3 . Conclusion : After 20 training sessions , G1 ( Adapted Physical Activities ) , G2 ( Wii Fit ® ) and G3 ( Adapted Physical Activities and Wii Fit ® ) improved their balance . In addition , G1 and G3 increased their dynamic balance . The findings suggest that Adapted Physical Activities training limits the decline in sensorial functions in the elderly Purpose : To examine the effectiveness of a novel intervention aim ed at decreasing indices related to frailty through systematic , Progressive Functional Rehabilitation ( PFR ) . Methods : Pre‐frail volunteers were recruited to participate in a 15 week exercise intervention or control group . Those who met study criteria and consented were r and omized into one of three groups : control , seated exercise , or Wii ® ‐fit . Test measures were completed before and after the 15 week intervention period on all participants . Measures included : Senior Fitness Test , Body Weight , Balance Efficacy Scale , CHAMPS , Late‐Life Function and Disability Index , MOS SF‐36 . Attendance was also recorded . Results : There were improvements on several of the measures included in the Senior Fitness Test including chair st and s , arm curls , step 2 , six minute walk , sit and reach , and the timed up and go . A few participants did lose weight . All of the differences reflected improved physical functional status in the seated exercise or Wii‐fit groups compared with the control group . Discussion : Increased physical activity was beneficial for all who participated . There were improvements in physical performance scores on several of the measures on the senior fitness test in both the seated exercise and Wii‐fit groups . Participants in the Wii‐fit group also showed improvement in their reported caloric expenditure and balance confidence . Conclusion : This pilot study suggests a rehabilitation effect that was similar to the effect of community based senior fitness classes . A home video game console system with weight vest could be an effective alternative for pre‐frail senior adults to group exercise classes BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . BACKGROUND physical therapy interventions that increase functional strength and balance have been shown to reduce falls in older adults . AIM this study compared a virtual reality group ( VRG ) and a control group ( CG ) . DESIGN r and omised controlled 6-week intervention with pre- and post-test evaluations . SETTING outpatient geriatric orthopaedic and balance physical therapy clinic . POPULATION forty participants were r and omised into two groups . METHOD the VRG received three different Nintendo ® Wii FIT balance interventions three times per week for 6 weeks and the CG received no intervention . RESULTS compared with the CG , post-intervention measurements showed significant improvements for the VRG in the 8-foot Up & Go test [ median decrease of 1.0 versus -0.2 s , ( P=0.038 ) and the Activities-specific Balance Confidence Scale ( 6.9 versus 1.3 % ) ( P=0.038 ) ] . CONCLUSION virtual reality gaming provides clinicians with a useful tool for improving dynamic balance and balance confidence in older adults BACKGROUND Physical training to increase muscle strength and balance is considered useful for prevention of falls in older people . AIM This study compares conventional balance training with visual computer feedback training . DESIGN This was a r and omized controlled 12-week intervention trial with pre- and post-training evaluations . SETTING Out- patients referred to a geriatric falls and balance clinic . POPULATION Thirty-five patients were r and omized into two training groups . METHODS Both groups received progressive resistance muscle strength training and physical fitness training . Additionally , one group received traditional balance training and the other group received computer feedback balance training . Strength , physical endurance , balance and falls efficacy scale scoring were assessed before and after end of training . RESULTS Twenty-seven patients ( 77 % ) were available for the evaluation ; mean compliance was 71 % . In the combined group , significant mean improvement was observed in knee extension ( 19 % ) , ankle dorsiflexion ( 16 % ) , sitting to st and ing ( 16 % ) , and in the six-minute walk test ( 8 % ) . In the traditional balance training group , the static balance in the Modified Clinical Test of Sensory Interaction and Balance st and ing on a foam mat with closed eyes showed a significant increase ( 80 % ) . No increase occurred in the computer balance training group . However , the computer feed-back training group showed a marked improvement that was up to 400 % in the training specific performance . CONCLUSION Elderly frail patients were able to increase muscle strength and physical endurance . A limited improvement was seen in the static balance tests . The computer feedback group showed a remarkable increase in training specific performance . Clinical Rehabilitation Impact Background Due to the many problems associated with reduced balance and mobility , providing an effective and engaging rehabilitation regimen is essential to progress recovery from impairments and to help prevent further degradation of motor skills . Objectives The purpose of this study was to examine the feasibility and benefits of physical therapy based on a task-oriented approach delivered via an engaging , interactive video game paradigm . The intervention focused on performing targeted dynamic tasks , which included reactive balance controls and environmental interaction . Design This study was a r and omized controlled trial . Setting The study was conducted in a geriatric day hospital . Participants Thirty community-dwelling and ambulatory older adults attending the day hospital for treatment of balance and mobility limitations participated in the study . Interventions Participants were r and omly assigned to either a control group or an experimental group . The control group received the typical rehabilitation program consisting of strengthening and balance exercises provided at the day hospital . The experimental group received a program of dynamic balance exercises coupled with video game play , using a center-of-pressure position signal as the computer mouse . The tasks were performed while st and ing on a fixed floor surface , with progression to a compliant sponge pad . Each group received 16 sessions , scheduled 2 per week , with each session lasting 45 minutes . Measurements Data for the following measures were obtained before and after treatment : Berg Balance Scale , Timed “ Up & Go ” Test , Activities-specific Balance Confidence Scale , modified Clinical Test of Sensory Interaction and Balance , and spatiotemporal gait variables assessed in an instrumented carpet system test . Results Findings demonstrated significant improvements in posttreatment balance performance scores for both groups , and change scores were significantly greater in the experimental group compared with the control group . No significant treatment effect was observed in either group for the Timed “ Up & Go ” Test or spatiotemporal gait variables . Limitations The sample size was small , and there were group differences at baseline in some performance measures . Conclusion Dynamic balance exercises on fixed and compliant sponge surfaces were feasibly coupled to interactive game-based exercise . This coupling , in turn , result ed in a greater improvement in dynamic st and ing balance control compared with the typical exercise program . However , there was no transfer of effect to gait function |
12,132 | 19,212,898 | These reported principally that altering lower limb joint orientation or the addition of a co-contraction does not preferentially enhance VMO activity over VL . | Debate exists as to whether the vastus medialis oblique ( VMO ) can be activated to a greater degree than the vastus lateralis to produce preferential strengthening .
This systematic review aims to determine whether preferential activation of VMO can be achieved by altering lower limb joint orientation or muscular co-contraction . | The purpose of this study was to compare the effect of an open-stance cycling protocol ( OSCP ) with the traditional cycling foot position ( TCFP ) for preferential vastus medialis oblique ( VMO ) muscle activation , measured by surface electromyography ( SEMG ) , and preferential VMO activation as defined by achieving significantly increased VMO/VL ( vastus lateralis muscle ) ratio values . Forty subjects of both sexes participated , 18 symptomatic with patellofemoral pain and 22 control subjects ; ages ranged from 18 to 60 years ( mean 5 28.7 ± 8 years ) . The OSCP and TCFP were ridden in r and omized order while SEMG recordings were taken of the VMO and VL muscles , collecting the mean of peak amplitudes to calculate VMO/VL ratio values . The SEMG readings were taken 4 times per testing session with r and omized resistance and a consistent cycling cadence of 85 rpm . The OSCP displayed preferential VMO activation for all subject groups ( F = 40.47 , p = 0.0001 ) , and this study revealed a protocol that effectively treats patellofemoral pain Strengthening of the vastus medialis oblique ( VMO ) has been advocated as a treatment for patellofemoral pain syndrome ( PFPS ) , as weakness of this component of the quadriceps is postulated to contribute to malalignment of the patella . This study investigated the surface electromyographic activity ( EMG ) of the VMO relative to the vastus lateralis ( VL ) during five isometric exercises in eight PFPS female subjects and 19 controls . The area under the EMG curve of each muscle was normalized to the EMG area acquired while subjects performed a submaximal isometric contraction ( 50 % of maximum voluntary contraction ) , and the " normalized " outcome measure was expressed as a proportion ( VMO : VL ) . A two-factor repeated measures analysis of variance indicated no differences in the VMO : VL proportion between the control group and PFPS participants across the five exercises ( p > .05 ) . The VMO : VL proportions for medial tibial rotation and knee extension combined and knee extension alone were significantly greater than for the other three exercises ( p < 0.005 ) . Hip adduction or the combination of hip adduction and knee extension did not result in greater recruitment of the VMO compared with the VL A prospect i ve study of 20 normal subjects was undertaken to determine the effect of three ankle positions ( active dorsiflexion , active plantar flexion , natural or rest position ) on comfort and facilitation of quadriceps contraction in isometric strengthening in a supine position with the hip and knee fully extended . Surface EMG activity was found to be greatest for the vastus lateralis followed by the vastus medialis and least for the rectus femoris . Equal facilitation was apparent with either active ankle dorsiflexion or plantar flexion . Both were superior to the natural ( rest ) position . In situations where isometric quadriceps exercises are required , the authors recommend either active ankle dorsiflexion or plantar flexion to facilitate quadriceps strengthening . The choice between the two positions should be based on patient comfort OBJECTIVE The purpose of this study was to investigate the effect of hip adduction on the activity of the Vastus Medialis Obliquus ( VMO ) and Vastus Lateralis Longus ( VLL ) muscles during semisquat exercises . METHODS Twenty female subjects , divided into two groups comprising healthy and patellofemoral pain syndrome ( PFPS ) subjects ( ten volunteers for each group ) , performed three double-leg semisquat exercise trials with maximum hip adduction isometric contraction ( DLSS-HA ) and three double-leg semisquat exercise trials without hip adduction ( DLSS ) . The normalized electromyographic muscle data were analysed using Repeated Measure ANOVA ( p < or=0.05 ) . RESULTS The electrical activity of both VMO and VLL muscles was significantly greater during DLSS-HA exercise than during DLSS ( p=0.0002 ) for both groups . Additionally , an independent Repeated Measure ANOVA revealed that the electric activity of the VLL muscle was significantly greater ( p=0.0149 ) than that of the VMO muscle during DLSS exercises only for the PFPS group . However , no differences were found during DLSS-HA exercises . CONCLUSIONS Although there was no preferential VMO muscle activation , the association of hip adduction with squat exercise promoted a greater balance between the medial and lateral portions of the quadriceps femoris muscle and could be indicated for the conservatory treatment of PFPS patients . The association of isometric hip adduction with isometric semisquat exercises produced a more overall quadriceps activity and could be indicated for clinical rehabilitation or muscle strengthening programs Lam PL , Ng GYF : Activation of the quadriceps muscle during semisquatting with different hip and knee positions in patients with anterior knee pain . Am J Phys Med Rehabil 2001;80:804–808 . Objective We measured the surface electromyographic activities of vastus medialis obliquus and vastus lateralis in 16 subjects with patellofemoral joint pain syndrome . Design Each subject performed bilateral static knee extension exercises at 60 % of his or her maximal voluntary effort under different combinations of hip rotation ( 30 degrees of medial rotation , neutral , 45 degrees of lateral rotation ) and knee flexion ( 20 and 40 degrees ) in a st and ing position . The ratio of surface-integrated electromyographic signals of vastus medialis obliquus over vastus lateralis was calculated for each of the six conditions . Because of significant interaction of hip rotation and knee flexion in the two-way analysis of variance , data were analyzed separately with paired t tests for the effect of knee positions and one-way repeated measures analysis of variance for hip positions . Results At 20 degrees of knee flexion , there was no significant difference among the three hip positions , whereas at 40 degrees of knee flexion , medial rotation of the hip result ed in significantly higher vastus medialis obliquus over vastus lateralis activity ratio than lateral rotation ( P < 0.05 ) . Conclusions There was relatively more activation of vastus medialis obliquus than vastus lateralis at 40 degrees of semisquat with the hip medially rotated by 30 degrees . This finding has clinical implication s for training the vastus medialis obliquus in patients with patellofemoral joint pain syndrome The purpose of this study was to determine whether various positions of the lower extremity affect the muscle activity of the vastus medialis obliquus ( VMO ) differently during both open and closed kinetic chain exercise conditions among patients with patellofemoral pain syndrome ( PFPS ) . Patients who presented with symptoms consistent with PFPS completed a series of open kinetic chain and closed kinetic chain exercises in which VMO activity was measured and compared . Statistical analysis revealed that there is less than a 0.001 % ( open kinetic chain ) or 0.005 % ( closed kinetic chain ) chance that all positions activate the VMO equally . In open kinetic exercise , maximum VMO activity was achieved with terminal knee extension with medial tibial rotation . During closed kinetic exercises , squats with external rotation were preferred for maximum VMO activation . Therefore , our results highlight the importance of including both the open and closed kinetic chain exercises into rehabilitation programs for patients with PFPS Nondriving intersegmental knee moment components ( i.e. , varus/valgus and internal/external axial moments ) are thought to be primarily responsible for the etiology of overuse knee injuries such as patellofermoral pain syndrome in cycling because of their relationship to muscular imbalances . However the relationship between these moments and muscle activity has not been studied . Thus the four primary objectives of this study were to test whether manipulating the inversion/eversion foot angle alters the varus/valgus knee moment ( Objective 1 ) and axial knee moment ( Objective 2 ) and to determine whether activation patterns of the vastus medialis oblique ( VMO ) , vastus lateralis ( VL ) , and tensor fascia latae ( TFL ) were affected by changes in the varus/valgus ( Objective 3 ) and axial knee moments ( Objective 4 ) . To fulfill these objectives , pedal loads and lower limb kinematic data were collected from 15 subjects who pedaled with five r and omly assigned inversion/eversion angles : 10 deg and 5 deg everted and inverted and 0 deg ( neutral ) . A previously described mathematical model was used to compute the nondriving intersegmental knee moments throughout the crank cycle . The excitations of the VMO , VL , and TFL muscles were measured with surface electromyography and the muscle activations were computed . On average , the 10-deg everted position decreased the peak varus moment by 55 % and decreased the peak internal axial moment by 53 % during the power stroke ( crank cycle region where the knee moment is extensor ) . A correlation analysis revealed that the VMO/VL activation ratio increased significantly and the TFL activation decreased significantly as the varus moment decreased . For both the VMO/VL activation ratio and the TFL activation , a path analysis indicated that the varus/valgus moment was highly correlated to the axial moment but that the correlation between muscle activation and the varus moment was due primarily to the varus/valgus knee moment rather than the axial knee moment . The conclusion from these results is that everting the foot may be beneficial towards either preventing or ameliorating patellofemoral pain syndrome in cycling PURPOSE To investigate the effect of physical therapy treatment on the timing of electromyographic ( EMG ) activity of the vasti in individuals with patellofemoral pain syndrome ( PFPS ) . METHODS Sixty-five ( 42 female , 23 male ) participants aged 40 yr or less ( 29.2 + /- 7.8 yr ) diagnosed with PFPS . Participants were r and omly allocated into physical therapy treatment ( McConnell-based ) or placebo groups . Treatment programs were st and ardized and consisted of six-treatment sessions over 6 wk . Vastus medialis oblique ( VMO ) and vastus lateralis ( VL ) EMG activity was recorded with surface electrodes during a stair-stepping task and onsets of EMG activity were measured pre- and post-treatment . RESULTS Before treatment , the EMG onset of VL occurred before that of VMO in both participant groups . After physical therapy intervention , there was a reduction in symptoms , and this improvement was associated with a significant change in the time of onset of VMO EMG compared with that of VL in both phases of the stair-stepping task . After physical therapy treatment , the onset of VMO preceded VL in the eccentric phase and occurred at the same time in the concentric phase of the stair-stepping task . There was no change in time of EMG onset in the placebo group . CONCLUSION This study demonstrates that a " McConnell"-based physical therapy treatment regime for PFPS alters the motor control of VMO relative to VL in a functional task and this is associated with a positive clinical outcome The clinical application of EMG requires that the recorded signal is representative of the muscle of interest and is not contaminated with signals from adjacent muscles . Some authors report that surface EMG is not suitable for obtaining information on a single muscle but rather reflects muscle group function [ J. Perry , C.S. Easterday , D.J. Antonelli , Surface versus intramuscular electrodes for electromyography of superficial and deep muscles . Physical Therapy 61 ( 1981 ) 7 - 15 ] . Other authors report however , that surface EMG is adequate to determine individual muscle function , once guidelines pertaining to data acquisition are followed [ D.A. Winter , A.J. Fuglev and , S.E. Archer . Cross-talk in surface electromyography : theoretical and practical estimates . Journal of Electromyography and Kinesiology 4 ( 1994 ) 15 - 26 ] . The aim of this study was to determine whether surface EMG was suitable for monitoring rectus femoris ( RF ) activity during static contractions . Five healthy subjects , having given written informed consent , participated in this trial . Surface and fine wire EMG from the rectus femoris and the vastus lateralis ( VL ) muscles were recorded simultaneously during a protocol of static contractions consisting of knee extensions and hip flexions . Ratios were used to quantify the relationship between the surface EMG amplitude value and the fine wire EMG amplitude value for the same contraction . The results showed that hip flexion contractions elicited RF activation only and that knee extension contractions elicited fine wire activity in VL only . When the relationship between RF surface and RF fine wire electrodes was compared for hip flexion and knee extension contractions , it was observed that for all subjects , there was a tendency for increased RF surface activity in the absence of RF fine wire activity during knee extensions . It was concluded that the activity recorded by the RF surface electrode arrangement during knee extension consisted of EMG from the vastii , i.e. , cross-talk and that vastus intermedius was the most likely origin of the erroneous signal . Therefore it is concluded that for accurate EMG information from RF , fine wire electrodes are necessary during a range of static contractions PURPOSE This study aim ed to examine whether a physical therapy intervention , design ed to reduce pain and improve the neuromotor control result ed in greater improvements in stance-phase knee flexion during stair ambulation in individuals with patellofemoral pain . The relationship between changes in stance-phase knee flexion and changes in pain , disability , and onset timing of individual vasti activity was also examined . METHODS Forty participants aged 40 yr or younger diagnosed with patellofemoral pain were r and omly allocated to a physical therapy ( N = 21 ) or placebo ( N = 19 ) treatment group . Stance-phase knee flexion was measured in two dimensions using a PEAK movement analysis system during stair ambulation . Individuals were divided into those with improvements in onset of vastus medialis obliquus ( VMO ) activity relative to that of the vastus lateralis ( VL ) of more or less than 10 ms . RESULTS Groups were similar at baseline . After the 6-wk intervention , individuals in the physical therapy group had significantly greater changes in knee flexion at heel strike ( mean difference 4 degrees , 95 % CI = 2 - 7 degrees ) and peak stance-phase knee flexion ( mean difference 9 degrees , 95 % CI = 5 - 12 degrees ) than those in the placebo group . No differences were noted during stair ascent . Individuals with greater change in the onset timing of the vasti had greater improvements in stance-phase knee flexion . Changes in usual pain in the week before testing and change in the vasti onset timing were independent predictors of change in stance-phase knee flexion during stair descent , together accounting for 27 - 40 % of the variability in knee motion . CONCLUSIONS Physical therapy intervention result ed in significantly greater changes in knee joint motion than a placebo treatment , and these changes in knee motion were partly related to changes in pain and changes in onset timing of the vasti Little research is available on the muscle activity patterns of the lower extremity muscles during dynamic closed chain squatting activities . The purpose of this study was to examine the effect of lower extremity position during an Olympic squat on the muscle activity patterns of the vastus medialis , vastus lateralis , semimembranosus/semitendinosus , and biceps femoris . Twenty-five healthy , untrained subjects , 18 - 35 years old , were r and omly assigned initial squatting positions of either self-selected neutral or 30 degrees of lower extremity turn-out from the self-selected neutral position . Surface electromyography and motion analysis data were collected simultaneously in 10 degrees intervals and analyzed from 10 - 60 degrees of knee flexion in both the ascending and descending phases of the squat . A four-way analysis of variance indicated that the main effect of lower extremity position and the interaction of extremity position and knee joint angles were not found to cause significant changes in muscle activity patterns . Significant changes in muscle activity did occur with changes in knee flexion angles in the vastus medialis and vastus lateralis but not in the semimembranosus/semitendinosus or biceps femoris OBJECTIVE To determine the effects of a weight-bearing rehabilitation program on quadriceps and gluteus medius electromyographic activity , pain , and function in subjects diagnosed with patellofemoral pain syndrome ( PFPS ) . DESIGN Pretest and posttest 6-week intervention study . SETTING Musculoskeletal research laboratory . PARTICIPANTS Fourteen subjects diagnosed with PFPS and 14 healthy control subjects volunteered to participate in this study . No subjects withdrew from the study because of adverse effects . INTERVENTION Subjects diagnosed with PFPS participated in a 6-week rehabilitation program . The rehabilitation program consisted of weight-bearing exercises that focused on strengthening the quadriceps and hip abductor musculature . MAIN OUTCOME MEASURES Electromyographic onsets of the vastus medialis oblique ( VMO ) and vastus lateralis and onset and duration of the gluteus medius were collected during a stair-stepping task that was performed during the pretest and posttest . A visual analog scale ( VAS ) and Functional Index Question naire ( FIQ ) were administered at pretest and posttest and each week of the intervention . RESULTS Vastus lateralis and VMO onset timing differences ( vastus lateralis electromyographic onset minus VMO electromyographic onset ) and VAS and FIQ scores significantly improved for patients diagnosed with PFPS . Vastus lateralis and VMO onset timing in the PFPS group were significantly different from those in the control group at baseline and were not significantly different from the control group after the intervention . We did not find differences in gluteus medius onsets or duration of activity . CONCLUSIONS Subjects diagnosed with PFPS responded favorably and quickly to a therapeutic exercise program that incorporated quadriceps and hip musculature strengthening . The efficacy of the therapeutic exercise program used in this study should be further investigated in a larger subject population BACKGROUND Recent studies have shown excellent clinical results using eccentric squat training on a 25 degrees decline board to treat patellar tendinopathy . It remains unknown why therapeutic management of patellar tendinopathy using decline eccentric squats offer superior clinical efficacy compared to st and ard horizontal eccentric squats . This study aim ed to compare electromyography activity , patellar tendon strain and joint angle kinematics during st and ard and decline eccentric squats . METHODS Thirteen subjects performed unilateral eccentric squats on flat- and a 25 degrees decline surface . During the squats , electromyography activity was obtained in eight representative muscles . Also , ankle , knee and hip joint goniometry was obtained . Additionally , patellar tendon strain was measured in vivo using ultrasonography as subjects maintained a unilateral isometric 90 degrees knee angle squat position on either flat or 25 degrees decline surface . FINDINGS Patellar tendon strain was significantly greater ( P<0.05 ) during the squat position on the decline surface compared to the st and ard surface . The stop angles of the ankle and hip joints were significantly smaller during the decline compared to the st and ard squats ( P<0.001 , P<0.05 ) . Normalized mean electromyography amplitudes of the knee extensor muscles were significantly greater during the decline compared to the st and ard squats ( P<0.05 ) . Hamstring and calf muscle mean electromyography did not differ , respectively , between st and ard and decline squats . INTERPRETATION The use of a 25 degrees decline board increases the load and the strain of the patellar tendon during unilateral eccentric squats . This finding likely explains previous reports of superior clinical efficacy of decline eccentric squats in the rehabilitative management of patellar tendinopathy |
12,133 | 24,385,461 | Use of a control intervention did not moderate effect size in any of the analyses .
There was no consistent evidence of publication bias across different analyses .
Cognitive-behavioural therapy has a therapeutic effect on schizophrenic symptoms in the ' small ' range . | BACKGROUND Cognitive-behavioural therapy ( CBT ) is considered to be effective for the symptoms of schizophrenia .
However , this view is based mainly on meta- analysis , whose findings can be influenced by failure to consider sources of bias .
AIMS To conduct a systematic review and meta- analysis of the effectiveness of CBT for schizophrenic symptoms that includes an examination of potential sources of bias . | BACKGROUND Persistent drug-resistant psychotic symptoms are a pervasive problem in the treatment of schizophrenia . AIMS To evaluate the durability of the treatment effects of cognitive-behavioural therapy for chronic schizophrenia one year after treatment termination . METHOD A comparison of clinical outcomes was made at one-year follow-up from a r and omised trial of cognitive-behavioural therapy , supportive counselling and routine care alone in the treatment of chronic schizophrenia . RESULTS Seventy out of the 72 patients ( 97 % ) who completed treatment were assessed at follow-up . There were significant differences between the three groups when positive and negative symptoms were analysed by means of ANCOVAs . Between-group comparisons indicated significant differences between cognitive-behavioural therapy and routine care at follow-up for positive symptoms . There was a trend towards significance for both cognitive-behavioural therapy and supportive counselling to be superior to routine care alone on negative symptoms . CONCLUSIONS At 12-month follow-up the significant advantage of cognitive-behavioural therapy compared to routine care alone remained BACKGROUND Comm and hallucinations are a distressing and high-risk group of symptoms that have long been recognised but little understood , with few effective treatments . In line with our recent research , we propose that the development of an effective cognitive therapy for comm and hallucinations ( CTCH ) would be enhanced by applying insights from social rank theory . AIMS We tested the efficacy of CTCH in reducing beliefs about the power of voices and thereby compliance , in a single-blind , r and omised controlled trial . METHOD A total of 38 patients with comm and hallucinations , with which they had recently complied with serious consequences , were allocated r and omly to CTCH or treatment as usual and followed up at 6 months and 12 months . RESULTS Large and significant reductions in compliance behaviour were obtained favouring the cognitive therapy group ( effect size 1.1 ) . Improvements were also observed in the CTCH but not the control group in degree of conviction in the power and superiority of the voices and the need to comply , and in levels of distress and depression . No change in voice topography ( frequency , loudness , content ) was observed . The differences were maintained at 12 months ' follow-up . CONCLUSIONS The results support the efficacy of cognitive therapy for CTCH Comm and hallucinations represent a special problem for the clinical management of psychosis . While compliance with both non-harmful and harmful comm and s can be problematic , sometimes in the extreme , active efforts to resist comm and s may also contribute to their malignancy . Previous research suggests Cognitive Behaviour Therapy ( CBT ) to be a useful treatment for reducing compliance with harmful comm and hallucinations . The purpose of this trial was to evaluate whether CBT augmented with acceptance-based strategies from Acceptance and Commitment Therapy could more broadly reduce the negative impact of comm and hallucinations . Forty-three participants with problematic comm and hallucinations were r and omized to receive 15 sessions of the intervention " TORCH " ( Treatment of Resistant Comm and Hallucinations ) or the control , Befriending , then followed up for 6 months . A sub- sample of 17 participants was r and omized to a waitlist control before being allocated to TORCH or Befriending . Participants engaged equally well with both treatments . Despite TORCH participants subjectively reporting greater improvement in comm and hallucinations compared to Befriending participants , the study found no significant group differences in primary and secondary outcome measures based on blinded assessment data . Within-group analyses and comparisons between the combined treatments and waitlist suggested , however , that both treatments were beneficial with a differential pattern of outcomes observed across the two conditions OBJECTIVE Patients with first-episode psychosis are responsive to acute-phase treatments , but relapse rates are high . This study aim ed to evaluate the effectiveness of a psychosocial treatment design ed to prevent the second episode of psychosis compared with st and ardized early psychosis care . METHOD In a r and omized controlled trial , conducted at the Early Psychosis Prevention and Intervention Centre and Barwon Health , Australia , a multimodal individual and family cognitive-behavioral therapy for relapse prevention was compared with st and ardized case management within a specialist early psychosis service . Patients aged 15 to 25 years with a first episode of a DSM-IV psychotic disorder were recruited between November 2003 and May 2005 . The main outcome measures were the number of relapses and time to first relapse . RESULTS Forty-one first-episode psychosis patients were r and omly assigned to the relapse prevention therapy ( RPT ) and 40 to st and ardized case management . At the 7-month follow up , the relapse rate was significantly lower in the therapy condition compared to treatment as usual ( p = .042 ) and time to relapse was significantly longer for the RPT condition ( p = .03 ) . The number needed to treat was 6 over 7 months . CONCLUSIONS Interim findings suggest that RPT provided within a specialist early psychosis program was effective in reducing relapse in early psychosis when compared with st and ardized early psychosis case management . TRIAL REGISTRATION www.anzctr.org.au Identifier : ACTRN12605000514606 BACKGROUND There is increasing evidence that cognitive-behavioural therapy can be an effective intervention for patients experiencing drug-refractory positive symptoms of schizophrenia . AIMS To investigate the effects of cognitive-behavioural therapy on in- patients with treatment-refractory psychotic symptoms . METHOD Manualised therapy was compared with supportive counselling in a r and omised controlled study . Both interventions were delivered by experienced psychologists over 16 sessions of treatment . Therapy fidelity was assessed by two independent raters . Participants underwent masked assessment at baseline , after treatment and at 6 months ' follow-up . Main outcome measures were the Positive and Negative Syndrome Scale and the Psychotic Symptoms Rating Scale . The analysis was by intention to treat . RESULTS Participants receiving cognitive cognitive-behavioural therapy had improved with regard to auditory hallucinations and illness insight at the post-treatment assessment , but these findings were not maintained at follow-up . CONCLUSIONS Cognitive-behavioural therapy showed modest short-term benefits over supportive counselling for treatment-refractory positive symptoms of schizophrenia BACKGROUND Family intervention reduces relapse rates in psychosis . Cognitive-behavioural therapy ( CBT ) improves positive symptoms but effects on relapse rates are not established . AIMS To test the effectiveness of CBT and family intervention in reducing relapse , and in improving symptoms and functioning in patients who had recently relapsed with non-affective psychosis . METHOD A multicentre r and omised controlled trial ( IS RCT N83557988 ) with two pathways : those without carers were allocated to treatment as usual or CBT plus treatment as usual , those with carers to treatment as usual , CBT plus treatment as usual or family intervention plus treatment as usual . The CBT and family intervention were focused on relapse prevention for 20 sessions over 9 months . RESULTS A total of 301 patients and 83 carers participated . Primary outcome data were available on 96 % of the total sample . The CBT and family intervention had no effects on rates of remission and relapse or on days in hospital at 12 or 24 months . For secondary outcomes , CBT showed a beneficial effect on depression at 24 months and there were no effects for family intervention . In people with carers , CBT significantly improved delusional distress and social functioning . Therapy did not change key psychological processes . CONCLUSIONS Generic CBT for psychosis is not indicated for routine relapse prevention in people recovering from a recent relapse of psychosis and should currently be reserved for those with distressing medication-unresponsive positive symptoms . Any CBT targeted at this acute population requires development . The lack of effect of family intervention on relapse may be attributable to the low overall relapse rate in those with carers UNLABELLED Cognitive behavioural therapy ( CBT ) is recommended in treatment guidelines for psychotic symptoms ( NICE , 2009 ) but clients from some minority groups have been shown to have higher dropout rates and poorer outcomes . A recent qualitative study in ethnic minority groups concluded that CBT would be acceptable and may be more effective if it was culturally adapted to meet their needs ( Rathod et al. , 2010 ) . AIM This study assessed the effectiveness of a culturally adapted CBT for psychosis ( CaCBTp ) in Black British , African Caribbean/Black African and South Asian Muslim participants . METHOD A r and omised controlled trial was conducted in two centres in the UK ( n=35 ) in participants with a diagnosis of a disorder from the schizophrenia group . Assessment s were conducted at three time points : baseline , post-therapy and at 6 months follow-up , using the Comprehensive Psychopathological Rating Scale ( CPRS ) and Insight Scale . Outcomes on specific subscales of CPRS were also evaluated . Participants in the treatment arm completed the Patient Experience Question naire ( PEQ ) to measure satisfaction with therapy . Assessors blind to r and omisation and treatment allocation conducted administration of outcome measures . In total , n=33 participants were r and omly allocated to CaCBTp arm ( n=16 ) and treatment as usual ( TAU ) arm ( n=17 ) after ( n=2 ) participants were excluded . CaCBTp participants were offered 16 sessions of CaCBTp with trained therapists and the TAU arm continued with their st and ard treatment . RESULTS Analysis was based on the principles of intention to treat ( ITT ) . This was further supplemented with secondary sensitivity analyses . Post-treatment , the intervention group showed statistically significant reductions in symptomatology on overall CPRS scores , CaCBTp Mean (SD)=16.23 ( 10.77 ) , TAU=18.60 ( 14.84 ) ; p=0.047,with a difference in change of 11.31 ( 95 % CI:0 . 14 to 22.49 ) ; Schizophrenia change : CaCBTp=3.46 ( 3.37 ) ; TAU=4.78 ( 5.33 ) diff 4.62 ( 95 % CI : 0.68 to 9.17 ) ; p=0.047 and positive symptoms ( delusions ; p=0.035 , and hallucinations ; p=0.056 ) . At 6 months follow-up , MADRAS change=5.6 ( 95 % CI : 2.92 to 7.60 ) ; p<0.001 . Adjustment was made for age , gender and antipsychotic medication . Overall satisfaction was significantly correlated with the number of sessions attended ( r=0.563 ; p=0.003 ) . CONCLUSION Participants in the CaCBTp group achieved statistically significant results post-treatment compared to those in the TAU group with some gains maintained at follow-up . High levels of satisfaction with the CaCBTp were reported Objective : The objective of this study was to investigate the efficacy of group-based cognitive-behavioural therapy ( CBT ) for social anxiety in schizophrenia . Method : Patients with schizophrenia ( 20 ) with comorbid social anxiety were r and omly assigned to the group-based CBT or wait-list control condition . Pre- , post- and 6-week follow-up ratings included measures of social anxiety and avoidance , mood and quality of life . Results : The intervention group improved on all outcome measures and the control group showed no change in symptomatology . Conclusions : Group-based CBT is effective in treating social anxiety in schizophrenia Background : Recent research indicates that cognitive-behaviour therapy ( CBT ) can be effective in ameliorating persistent positive symptoms in chronic psychotic patients . The effectiveness of CBT in acute and recent-onset psychosis has been little explored , although a recent pilot study indicated that CBT could significantly improve recovery in acutely psychotic in patients . Method : Short-term individual CBT was compared to supportive counselling/psychoeducation ( SC ) as an adjunct to st and ard inpatient hospital care and medication in 21 in patients experiencing a recent-onset acute schizophrenic episode . Results : Both groups showed significant reductions in Brief Psychiatric Rating Scale ( BPRS ) scores following treatment , although there were no group differences . Time to discharge did not differ significantly between the groups , although there was a greater variance for the SC patients . Two-year follow-up showed no significant differences between the groups , although the number of patients who relapsed , the number of relapses and the time to recurrence of psychotic symptoms was lower in the CBT group than the SC group . Interestingly , the time to readmission was shorter in the CBT group . Conclusions : CBT and SC are acceptable treatments for recent-onset acutely psychotic in patients . A larger r and omised controlled trial over multiple hospital sites is warranted Emerging models of cognitive-behavioral treatment ( CBT ) offer promising new intervention strategies in the psychotherapy of schizophrenia . These models , however , have not been integrated into community support programs and evaluated in comparison to st and ard community treatments . This study examined differences in outcomes of clients who received long-term day treatment program services ( DTP ) compared to clients who received individual CBT that was included as part of their DTP treatment . Twenty-four clients were r and omly assigned to DTP treatment or CBT/DTP treatment . Data on st and ardized measures of psychosocial functioning , symptomatology and rehospitalizations were collected over the course of three years of treatment . Analysis of variance with repeated measures was conducted to evaluate the effects of type of treatment ( CBT/DTP and DTP ) and time ( dependent variable scores taken at the end of treatment years one , two and three ) on the three outcome variables . Results indicate significant improvement for the CBT/DTP group compared to the DTP group in the patterns of change over time for psychosocial functioning and symptomology . In addition to this significant group/time interaction the time factor was also significant for both variables . For rehospitalizations the time factor was significant and the group/time factor was nonsignificant . Implication s for service delivery to persons with schizophrenia and suggestions for future research are discussed Low self esteem in individuals with a psychotic disorder is common and may be related to poorer clinical outcomes . However , there has been little research on devising treatment methods to improve self-esteem either generally or in psychotic patients in particular . The aims of this study were to evaluate the efficacy of a simple cognitive behavioural intervention to improve self esteem in psychotic patients who scored poorly on a self-esteem measure . This pilot study was a r and omised control trial with a convenience sample of chronic psychotic in patients . The cognitive behavioural self-esteem intervention , as an adjunct to treatment as usual ( TAU ) , was compared to TAU alone in patients with psychosis . The individual self-esteem intervention as described by Tarrier ( The use of coping strategies and self-regulation in the treatment of psychosis . ( 2001 ) ) consisted of working with participants to elicit positive self-attributes and then identify specific behavioural examples to provide evidence of this attribute . Emphasis was given to any consequential change in the patient 's belief that they had the attribute . The results indicated that this cognitive behavioural treatment for self-esteem used as an adjunct treatment in psychosis , result ed in clinical benefits in terms of increased self-esteem , decreased psychotic symptomatology and improved social functioning . These benefits were largely maintained at 3-month follow-up BACKGROUND The aim of the current study was to assess whether patients with a DSM-IV diagnosis of schizophrenia and experiencing persistent positive and negative symptoms improve with the addition of cognitive-behavioural therapy to enriched st and ard treatment . METHODS A controlled study was completed with 42 patients r and omized to either cognitive-behavioural therapy plus enriched treatment-as-usual ( CBT-ETAU ) ( n = 24 ) or enriched treatment-as-usual only ( ETAU ) ( n = 18 ) . Enriched treatment-as-usual comprised comprehensive treatment within specialised schizophrenia treatment services . Cognitive-behavioural therapy was conducted on an individual basis for 6 months ( 20 sessions ) . Clinical assessment s were done at pretreatment , posttreatment and at 6-month follow-up by raters blind to group allocation . RESULTS Significant clinical effects were observed for positive , negative and overall symptom severity for patients treated in CBT-ETAU , although there were no statistically significant differences between the treatment groups at posttreatment . The most pronounced effect of CBT-ETAU in comparison to ETAU in this study was in the reduction of negative symptoms at follow-up . CONCLUSION These results show promise for the impact of CBT on negative symptoms when explicitly targeted in treatment BACKGROUND The feasibility and preliminary efficacy of a novel cognitive behavioral treatment for decreasing psychotic symptoms and improving social functioning was evaluated in a pilot study . This represents the first treatment outcome study of CBT for psychosis with a manualized , active comparison condition . METHODS Thirty out patients with schizophrenia or schizoaffective disorder , depressed type with residual psychotic symptoms were r and omly assigned to either 16 weekly sessions of functional cognitive behavioral therapy ( fCBT ) or psychoeducation ( PE ) with assessment s conducted at baseline and post-treatment by blind evaluators . RESULTS Attrition was only 7 % and did not differ between fCBT and PE , indicating good tolerability of both treatments . For this sample with persistent symptoms , between groups effects were not significantly different , but within group effect sizes indicated greater treatment benefit for fCBT on positive symptoms , particularly for the PSYRATS voices subscale . CONCLUSION The results suggest that fCBT is well tolerated and holds promise for reducing persistent positive symptoms BACKGROUND Little evidence exists for the effects of psychological treatment on voices even though it is clear that CBT does affect delusions and symptoms overall . This study tested whether a group based on cognitive behavioural principles could produce beneficial effects on hallucinations . AIM To test the effectiveness of group CBT on social functioning and severity of hallucinations . METHOD Participants were included if they had a diagnosis of schizophrenia and experienced distressing auditory hallucinations ( rated on the PANSS ) . They were r and omly allocated to group CBT ( N = 45 ) or a control group who received treatment as usual ( N = 40 ) . The two main outcomes were social functioning as measured by the Social Behaviour Schedule and the severity of hallucinations as measured by the total score on the Hallucinations Scale of PSYRATS . Assessment s were carried out at baseline , 10 weeks ( post therapy ) and 36 weeks ( six months following therapy ) . RESULTS Mixed r and om effects models revealed significant improvement in social functioning ( effect size 0.63 six months after the end of therapy ) . There was no general effect of group CBT on the severity of hallucinations . However , there was a large cluster effect of therapy group on the severity of hallucinations such that they were reduced in some but not all of the therapy groups . Improvement in hallucinations was associated with receiving therapy early in the trial and having very experienced therapists ( extensive CBT training which included expert supervision for a series of individual cases for at least a year following initial training ) . CONCLUSION Group CBT does improve social functioning but unless therapy is provided by experienced CBT therapists hallucinations are not reduced Objective : This r and om‐controlled study evaluated benefits derived from continued integrated biomedical and psychosocial treatment for recent‐onset schizophrenia There are few evaluated psychological interventions or theoretical approaches which are specifically aim ed at reducing problems related to adjustment and adaptation following a first episode of psychosis . The present study tests the efficacy of a form of CBT ( Cognitive Recovery Intervention ; CRI ) in reducing trauma , depression and low self esteem following a first episode of psychosis , in a single-blind r and omised controlled trial . A total of 66 patients who had recently experienced a first episode of psychosis were r and omly assigned to CRI or treatment as usual ( TAU ) and followed up at 6 and 12 months . People receiving CRI tended to have lower levels of post-intervention trauma symptoms and demonstrated greater improvement than those receiving TAU alone . This was especially the case at 6 months for those with high pre-treatment levels of trauma . There was , however , no advantage for the CRI group with regards to reduced depression or improved self esteem . In conclusion , CRI appears to be an effective intervention to help young people adapt to the traumatic aspects of a first episode of psychosis although further evaluation in a larger study is warranted BACKGROUND This study reports on a preliminary evaluation of a cognitive behavioural intervention to improve social recovery among young people in the early stages of psychosis showing persistent signs of poor social functioning and unemployment . The study was a single-blind r and omized controlled trial ( RCT ) with two arms , 35 participants receiving cognitive behaviour therapy ( CBT ) plus treatment as usual ( TAU ) , and 42 participants receiving TAU alone . Participants were assessed at baseline and post-treatment . METHOD Seventy-seven participants were recruited from secondary mental health teams after presenting with a history of unemployment and poor social outcome . The cognitive behavioural intervention was delivered over a 9-month period with a mean of 12 sessions . The primary outcomes were weekly hours spent in constructive economic and structured activity . A range of secondary and tertiary outcomes were also assessed . RESULTS Intention-to-treat analysis on the combined affective and non-affective psychosis sample showed no significant impact of treatment on primary or secondary outcomes . However , analysis of interactions by diagnostic subgroup was significant for secondary symptomatic outcomes on the Positive and Negative Syndrome Scale ( PANSS ) [ F(1 , 69)=3.99 , p=0.05 ] . Subsequent exploratory analyses within diagnostic subgroups revealed clinical ly important and significant improvements in weekly hours in constructive and structured activity and PANSS scores among people with non-affective psychosis . CONCLUSIONS The primary study comparison provided no clear evidence for the benefit of CBT in a combined sample of patients . However , planned analyses with diagnostic subgroups showed important benefits for CBT among people with non-affective psychosis who have social recovery problems . These promising results need to be independently replicated in a larger , multi-centre RCT Here we report the results of a pilot study investigating the relative and combined effects of a 12 week course of clozapine and CBT in first-episode psychosis patients with prominent ongoing positive symptoms following their initial treatment . Patients from our early psychosis service who met the inclusion criteria ( n = 48 ) were r and omized to one of four treatment groups : clozapine , clozapine plus CBT , thioridazine , or thioridazine plus CBT . The degree of psychopathology and functionality of all participants was measured at baseline then again at 6 , 12 and 24 weeks , and the treatment outcomes for each group determined by statistical analysis . A substantial proportion ( 52 % ) of those treated with clozapine achieved symptomatic remission , as compared to 35 % of those who were treated with thioridazine . Overall , those who received clozapine responded more rapidly to treatment than those receiving the alternative treatments . Interestingly , during the early treatment phase CBT appeared to reduce the intensity of both positive and negative symptoms and thus the time taken to respond to treatment , as well having as a stabilizing effect over time Cognitive behavior therapy ( CBT ) has been demonstrated in a number of r and omized controlled trials to be efficacious as an adjunctive treatment for psychotic disorders . Emerging evidence suggests the usefulness of CBT interventions that incorporate acceptance/mindfulness-based approaches for this population . The current study extended previous research by Bach and Hayes ( 2002 . The use of Acceptance and Commitment Therapy to prevent the rehospitalization of psychotic patients : A r and omized controlled trial . Journal of Consulting and Clinical Psychology , 70 , 1129 - 1139 ) using Acceptance and Commitment Therapy ( ACT ) in the treatment of psychosis . Psychiatric in patients with psychotic symptoms were r and omly assigned to enhanced treatment as usual ( ETAU ) or ETAU plus individual sessions of ACT . At discharge from the hospital , results suggested short-term advantages in the ACT group in affective symptoms , overall improvement , social impairment , and distress associated with hallucinations . In addition , more participants in the ACT condition reached clinical ly significant symptom improvement at discharge . Although 4-month rehospitalization rates were lower in the ACT group , these differences did not reach statistical significance . Decreases in the believability of hallucinations during treatment were observed only in the ACT condition , and change in believability was strongly associated with change in distress after controlling for change in the frequency of hallucinations . Results are interpreted as largely consistent with the findings of Bach and Hayes and warrant further investigations with larger sample BACKGROUND The paper describes a r and omized controlled trial of targeting cognitive behavioural therapy ( CBT ) during prodromal or early signs of relapse in schizophrenia . We hypothesized that CBT would result in reduced admission and relapse , reduced positive and negative symptoms , and improved social functioning . METHOD A total of 144 participants with schizophrenia or a related disorder were r and omized to receive either treatment as usual ( TAU ) ( N = 72 ) or CBT+TAU ( N = 72 ) . Participants were prospect ively followed up between entry and 12 months . RESULTS At 12 months , 11 ( 15.3 % ) participants in the CBT group were admitted to hospital compared to 19 ( 26.4 % ) of the TAU group ( hazard ratio = 0.53 , P = 0.10 , 95 % CI 0.25 , 1.10 ) . A total of 13 ( 18.1 % ) participants in CBT relapsed compared to 25 ( 34.7 % ) in TAU ( hazard ratio = 0.47 , P < 0O05 , 95 % CI 0.24 , 0.92 ) . In addition , the CBT group showed significantly greater improvement in positive symptoms , negative symptoms , global psychopathology , performance of independent functions and prosocial activities . CONCLUSIONS The study provides evidence for the feasibility and effectiveness for targeting CBT on the appearance of early signs of relapse in schizophrenia . The results are discussed in context of the study 's method ological limitations There has been little research examining group cognitive-behavioral therapy ( CBT ) for schizophrenia , especially compared to an active control treatment . The purpose of this study was to investigate the effectiveness of group CBT for auditory hallucinations compared to an enhanced supportive therapy ( ST ) . Sixty five participants with schizophrenia spectrum disorders and persistent hallucinations were r and omly assigned to group CBT or enhanced group ST . Primary outcomes focused on beliefs about voices and global auditory hallucinations severity . Secondary outcomes included psychotic symptoms , self-esteem , social functioning , insight , depression , and hospitalization . Controlling for baseline levels , these outcomes were evaluated across post-treatment , 3 month and 12 month follow-ups . Participants who received enhanced ST were less likely to both resist voices and to rate them as less malevolent through 12-month follow-up relative to participants who received CBT . Group CBT was associated with lower general and total symptom scores on the PANSS through 12-month-followup relative to participants who received enhanced ST . Outcomes improved through 12-month follow-up in both therapy groups , with enhanced ST having more specific impact on auditory hallucinations , and CBT impacting general psychotic symptoms CONTEXT Low-functioning patients with chronic schizophrenia have high direct treatment costs and indirect costs incurred due to lost employment and productivity and have a low quality of life ; antipsychotic medications and psychosocial interventions have shown limited efficacy to promote improved functional outcomes . OBJECTIVE To determine the efficacy of an 18-month recovery-oriented cognitive therapy program to improve psychosocial functioning and negative symptoms ( avolition-apathy , anhedonia-asociality ) in low-functioning patients with schizophrenia . Design , Setting , and PARTICIPANTS A single-center , 18-month , r and omized , single-blind , parallel group trial enrolled 60 low-functioning , neurocognitively impaired patients with schizophrenia ( mean age , 38.4 years ; 33.3 % female ; 65.0 % African American ) . INTERVENTIONS Cognitive therapy plus st and ard treatment vs st and ard treatment alone . MAIN OUTCOME MEASURES The primary outcome measure was the Global Assessment Scale score at 18 months after r and omization . The secondary outcomes were scores on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms at 18 months after r and omization . RESULTS Patients treated with cognitive therapy showed a clinical ly significant mean improvement in global functioning from baseline to 18 months that was greater than the improvement seen with st and ard treatment ( within-group Cohen d , 1.36 vs 0.06 , respectively ; adjusted mean [ SE ] , 58.3 [ 3.30 ] vs 47.9 [ 3.60 ] , respectively ; P = .03 ; between-group d = 0.56 ) . Patients receiving cognitive therapy as compared with those receiving st and ard treatment also showed a greater mean reduction in avolition-apathy ( adjusted mean [ SE ] , 1.66 [ 0.31 ] vs 2.81 [ 0.34 ] , respectively ; P = .01 ; between-group d = -0.66 ) and positive symptoms ( hallucinations , delusions , disorganization ) ( adjusted mean [ SE ] , 9.4 [ 3.3 ] vs 18.2 [ 3.8 ] , respectively ; P = .04 ; between-group d = -0.46 ) at 18 months . Age was controlled in the analyses , and there were no meaningful group differences in baseline antipsychotic medications ( class or dosage ) or in medication changes during the course of the trial . CONCLUSION Cognitive therapy can be successful in promoting clinical ly meaningful improvements in functional outcome , motivation , and positive symptoms in low-functioning patients with significant cognitive impairment . Trial Registration clinical trials.gov Identifier : NCT00350883 CONTEXT Antipsychotic drugs are limited in their ability to improve the overall outcome of schizophrenia . Adding psychosocial treatment may produce greater improvement in functional outcome than does medication treatment alone . OBJECTIVE To evaluate the effectiveness of antipsychotic medication alone vs combined with psychosocial intervention on outcomes of early-stage schizophrenia . DESIGN R and omized controlled trial . SETTING Ten clinical sites in China . PARTICIPANTS Clinical sample of 1268 patients with early-stage schizophrenia treated from January 1 , 2005 , through October 31 , 2007 . Intervention Patients were r and omly assigned to receive antipsychotic medication treatment only or antipsychotic medication plus 12 months of psychosocial intervention consisting of psychoeducation , family intervention , skills training , and cognitive behavior therapy administered during 48 group sessions . MAIN OUTCOME MEASURES The rate of treatment discontinuation or change due to any cause , relapse or remission , and assessment s of insight , treatment adherence , quality of life , and social functioning . RESULTS The rates of treatment discontinuation or change due to any cause were 32.8 % in the combined treatment group and 46.8 % in the medication-alone group . Comparisons with medication treatment alone showed lower risk of any-cause discontinuation with combined treatment ( hazard ratio , 0.62 ; 95 % confidence interval , 0.52 - 0.74 ; P < .001 ) and lower risk of relapse with combined treatment ( 0.57 ; 0.44 - 0.74 ; P < .001 ) . The combined treatment group exhibited greater improvement in insight ( P < .001 ) , social functioning ( P = .002 ) , activities of daily living ( P < .001 ) , and 4 domains of quality of life as measured by the Medical Outcomes Study 36-Item Short Form Health Survey ( all P < or = .02 ) . Furthermore , a significantly higher proportion of patients receiving combined treatment obtained employment or accessed education ( P = .001 ) . CONCLUSION Compared with those receiving medication only , patients with early-stage schizophrenia receiving medication and psychosocial intervention have a lower rate of treatment discontinuation or change , a lower risk of relapse , and improved insight , quality of life , and social functioning . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00654576 BACKGROUND The application of cognitive therapy ( CT ) to psychosis is currently being developed in the UK . This paper reports a trial of CT in acute psychosis with the objective of hastening the resolution of positive symptoms and reducing residual symptoms . METHOD Of 117 patients with acute non-affective psychosis , 69 satisfied inclusion criteria and 40 proceeded to stratified r and omisation . The experimental intervention involving individual and group CT was compared with a group receiving matched hours of therapist input providing structured activities and informal support ; routine pharmacotherapy was provided by clinicians blind to group allocation . Patients were monitored weekly using self-report and mental state assessment s during admission and over the subsequent nine months . RESULTS Both groups showed a decline in positive symptoms but this was more marked in the CT group ( P < 0.001 ) . At 9 months 5 % of the CT group , v.56 % of the control group , showed moderate or severe residual symptoms . CONCLUSION CT appears to be a potent adjunct to pharmacotherapy and st and ard care for acute psychosis . Issues concerning internal and external validity of the study and opportunities for further research are discussed BACKGROUND The provision of early intervention services for people with psychosis is UK government policy , although evidence for benefit of such services is sparse . AIMS To evaluate the effects of a service providing specialised care for early psychosis ( the Lambeth Early Onset Team ) on clinical and social outcomes , and on service user satisfaction . METHOD One hundred and forty-four people with psychosis , presenting to mental health services for the first or second time ( if previously failed to engage in treatment ) , were r and omly allocated to care by the early onset team or to st and ard care . Information was obtained on symptoms , treatment adherence , social and vocational functioning , satisfaction and quality of life . Relapse and rehospitalisation data have been reported separately . RESULTS Outcomes for the participants treated by the early onset team were significantly better at 18 months for aspects of social and vocational functioning , satisfaction , quality of life and medication adherence . Symptom improvement did not significantly differ between the groups . CONCLUSIONS The provision of specialised care for early psychosis can achieve better outcomes . The study therefore provides support for current policy Improvements in psychopathology , subjective burden , and coping with voices after hallucination focused integrative treatment ( HIT ) were studied in chronic schizophrenic patients with persistent ( > 10 years ) , drug-refractory auditory hallucinations . In a r and omized controlled trial , routine care was compared with HIT pre- and posttreatment at a 9-month interval . Independent raters used semistructured interviews to assess burden , symptoms , and coping . Within-group improvements in both burden and psychopathology were most significant in the experimental group ( p < 0.05 ) after treatment . HIT patients showed change in applied coping strategies , but it did not reach statistical significance . Type and ( change in ) number of coping strategies did not seem related to outcome . The results suggest that HIT is a cost-effective practice that positively affects mental state in general , subjective burden , quality of life , and social functioning Objective : Although the efficacy of cognitive‐behavioural therapy ( CBT ) in schizophrenia has been established in a number of studies , no information is available on the differential efficacy of CBT in comparison with patient psychoeduction ( PE ) PURPOSE Studies show that focused intervention attenuates depreciatory hallucinations . DESIGN AND METHODS A repeated measures design was used in this r and omized controlled trial to determine the significance of any sustained abatement in the hallucinations of 65 persons suffering from schizophrenia . FINDINGS Participants exposed to usual care supplemented with cognitive nursing intervention reported less severe hallucinations 1 year following treatment than did participants exposed to usual care only . They were 13.7 times more likely to maintain a 3-point drop in their hallucination scores . PRACTICE IMPLICATION S It appears that the hallucinations of 1 in every 2.7 persons with schizophrenia will abate significantly with cognitive intervention Background : Young people with early psychosis are at particularly high risk of suicide . However , there is evidence that early intervention can reduce this risk . Despite these advances , first episode psychosis patients attending these new services still remain at risk . To address this concern , a program called LifeSPAN was established within the Early Psychosis Prevention and Intervention Centre ( EPPIC ) . The program developed and evaluated a number of suicide prevention strategies within EPPIC and included a cognitively oriented therapy ( LifeSPAN therapy ) for acutely suicidal patients with psychosis . We describe the development of these interventions in this paper . Method : Clinical audit and surveys provided an indication of the prevalence of suicidality among first episode psychosis patients attending EPPIC . Second , staff focus groups and surveys identified gaps in service provision for suicidal young people attending the service . Third , a suicide risk monitoring system was introduced to identify those at highest risk . Finally , patients so identified were referred to and offered LifeSPAN therapy whose effectiveness was evaluated in a r and omised controlled trial . Results : Fifty-six suicidal patients with first episode psychosis were r and omly assigned to st and ard clinical care or st and ard care plus LifeSPAN therapy . Forty-two patients completed the intervention . Clinical ratings and measures of suicidality and risk were assessed before , immediately after the intervention , and 6 months later . Benefits were noted in the treatment group on indirect measures of suicidality , e.g. , hopelessness . The treatment group showed a greater average improvement ( though not significant ) on a measure of suicide ideation . Conclusions : Early intervention in psychosis for young people reduces the risk of suicide . Augmenting early intervention with a suicide preventative therapy may further reduce this risk BACKGROUND Research evidence supports the efficacy of cognitive-behavioral therapy in the treatment of drug-refractory positive symptoms of schizophrenia . Although the cumulative evidence is strong , early controlled trials showed method ological limitations . METHODS A r and omized controlled design was used to compare the efficacy of manualized cognitive-behavioral therapy developed particularly for schizophrenia with that of a nonspecific befriending control intervention . Both interventions were delivered by 2 experienced nurses who received regular supervision . Patients were assessed by blind raters at baseline , after treatment ( lasting up to 9 months ) , and at a 9-month follow-up evaluation . Patients continued to receive routine care throughout the study . An assessor blind to the patients ' treatment groups rated the technical quality of audiotaped sessions chosen at r and om . Analysis was by intention to treat . RESULTS Ninety patients received a mean of 19 individual treatment sessions over 9 months , with no significant between-group differences in treatment duration . Both interventions result ed in significant reductions in positive and negative symptoms and depression . At the 9-month follow-up evaluation , patients who had received cognitive therapy continued to improve , while those in the befriending group did not . These results were not attributable to changes in prescribed medication . CONCLUSION Cognitive-behavioral therapy is effective in treating negative as well as positive symptoms in schizophrenia resistant to st and ard antipsychotic drugs , with its efficacy sustained over 9 months of follow-up OBJECTIVES To determine whether Cognitive Behavioral Social Skills Training ( CBSST ) is an effective psychosocial intervention to improve functioning in older consumers with schizophrenia , and whether defeatist performance attitudes are associated with change in functioning in CBSST . DESIGN An 18-month , single-blind , r and omized controlled trial . SETTING Outpatient clinic at a university-affiliated Veterans Affairs hospital . PARTICIPANTS Veteran and non-veteran consumers with schizophrenia or schizoaffective disorder ( N = 79 ) age 45 - 78 . INTERVENTIONS CBSST was a 36-session , weekly group therapy that combined cognitive behavior therapy with social skills training and problem-solving training to improve functioning . The comparison intervention , goal -focused supportive contact ( GFSC ) , was supportive group therapy focused on achieving functioning goals . MEASUREMENTS Blind raters assessed functioning ( primary outcome : Independent Living Skills Survey ) , CBSST skill mastery , positive and negative symptoms , depression , anxiety , defeatist attitudes , self-esteem , and life satisfaction . RESULTS Functioning trajectories over time were significantly more positive in CBSST than in GFSC , especially for participants with more severe defeatist performance attitudes . Greater improvement in defeatist attitudes was also associated with better functioning in CBSST , but not GFSC . Both treatments showed comparable significant improvements in amotivation , depression , anxiety , positive self-esteem , and life satisfaction . CONCLUSIONS CBSST is an effective treatment to improve functioning in older consumers with schizophrenia , and both CBSST and other supportive goal -focused interventions can reduce symptom distress , increase motivation and self-esteem , and improve life satisfaction . Participants with more severe defeatist performance attitudes may benefit most from cognitive behavioral interventions that target functioning . TRIAL REGISTRY Clinical Trials . Gov # NCT00237796 ( http:// clinical trials . gov/show/NCT00237796 ) BACKGROUND Recent review s of r and omized controlled trials have concluded that cognitive behaviour therapy ( CBT ) is effective , as an addition to st and ard care , in the treatment of people suffering from schizophrenia . Most of the trials have been conducted with stabilized out- patients . The aim of this trial was to evaluate the effectiveness of CBT for in- patients suffering acute psychotic episodes , when delivered under conditions representative of current clinical practice . METHOD Consecutive admissions meeting criteria were recruited . After screening , 43 were assigned at r and om to a treatment-as-usual ( TAU ) control group and 47 were assigned to TAU plus CBT . At baseline , 6 months and 12 months , patients were rated on symptoms and social functioning . CBT ( maximum 25 sessions ) began immediately after baseline assessment . RESULTS The CBT group gained greater benefit than the TAU group on symptoms and social functioning . A larger proportion of the CBT group ( 60 % ) than the TAU group ( 40 % ) showed reliable and clinical ly important change , and none of them ( v. 17 % ) showed reliable deterioration compared with baseline . CONCLUSIONS CBT for patients suffering acute psychotic episodes can produce significant benefits when provided under clinical ly representative conditions Abstract . Background : Despite considerable interest in early intervention in psychosis , the evidence base for its effectiveness is sparse . We aim ed to evaluate a new service in South London , UK , Croydon Outreach and Assertive Support Team ( COAST ) using a r and omised controlled trial ( RCT ) during its first year . Method : Referrals were taken from local adult community mental health teams of those with documented first service contact in the last 5 years and a diagnosis of any functional psychosis . Those who consented ( N = 59 ) were r and omised to COAST or treatment as usual ( TAU ) . COAST offered a range of interventions , including optimum atypical medication , psychological interventions ( individual cognitive behavioural therapy and family intervention if appropriate ) and a range of vocational and welfare help according to need . Whole team training was used to be able to offer these kinds of interventions . Results : Outcomes were evaluated at baseline , 6 months and 9 months on a range of st and ardised clinical and social measures . Overall both COAST and TAU clients improved over time , but there were no significant improvements for COAST clients ; a lack of significant results in the time x treatment interaction . There was a trend for COAST carers ’ quality of life to increase . Bed days were also less in COAST , but not significantly so . Conclusions : The lack of clearly demonstrated improvements for COAST is consistent with the published literature so far . The fact that both groups improved in symptoms and functioning over the year suggests that while access to early intervention is helpful , community adult mental health teams should aim to offer high quality input at any stage of psychosis in order to meet client and carer needs BACKGROUND Cognitive-behavioural therapy ( CBT ) improves persistent psychotic symptoms . AIMS To test the effectiveness of added CBT in accelerating remission from acute psychotic symptoms in early schizophrenia . METHOD A 5-week CBT programme plus routine care was compared with supportive counselling plus routine care and routine care alone in a multi-centre trial r and omising 315 people with DSM-IV schizophrenia and related disorders in their first ( 83 % ) or second acute admission . Outcome assessment s were blinded . RESULTS Linear regression over 70 days showed predicted trends towards faster improvement in the CBT group . Uncorrected univariate comparisons showed significant benefits at 4 but not 6 weeks for CBT v. routine care alone on Positive and Negative Syndrome Scale total and positive sub-scale scores and delusion score and benefits v. supportive counselling for auditory hallucinations score . CONCLUSIONS CBT shows transient advantages over routine care alone or supportive counselling in speeding remission from acute symptoms in early schizophrenia BACKGROUND Recent research progress showing the benefits of cognitive therapy in schizophrenia leaves the general psychiatrist unsure whether to attempt to use such techniques . AIMS To test whether cognitive-behavioural techniques are beneficial in the management of patients with schizophrenia in general psychiatric practice . METHOD A r and omised controlled study comparing the use of cognitive-behavioural techniques and befriending in schizophrenia . RESULTS Significant improvement in symptoms occurred in the group treated with cognitive-behavioural techniques but not in the befriending group . During the 6-month follow-up period the cognitive-behavioural group tended to have shorter periods in hospital . CONCLUSIONS General psychiatrists could help their patients with schizophrenia by using cognitive-behavioural techniques . Such techniques are well within the capability of general psychiatrists , but their application would involve more of the consultant 's time spent in direct contact with patients with psychoses BACKGROUND Aggression and violence are serious problems in schizophrenia . Cognitive-behavioural therapy ( CBT ) has been shown to be an effective treatment for psychosis although there have been no studies to date evaluating the impact of CBT for people with psychosis and a history of violence . AIMS To investigate the effectiveness of CBT on violence , anger , psychosis and risk outcomes with people who had a diagnosis of schizophrenia and a history of violence . METHOD This was a single-blind r and omised controlled trial of CBT v. social activity therapy ( SAT ) with a primary outcome of violence and secondary outcomes of anger , symptoms , functioning and risk . Outcomes were evaluated by masked assessors at 6 and 12 months ( trial registration : NRR NO50087441 ) . RESULTS Significant benefits were shown for CBT compared with control over the intervention and follow-up period on violence , delusions and risk management . CONCLUSIONS Cognitive-behavioural therapy targeted at psychosis and anger may be an effective treatment for reducing the occurrence of violence and further investigation of its benefits is warranted OBJECTIVE The number of older patients with chronic schizophrenia is increasing . There is a need for empirically vali date d psychotherapy interventions for these patients . Cognitive behavioral social skills training teaches cognitive and behavioral coping techniques , social functioning skills , problem solving , and compensatory aids for neurocognitive impairments . The authors compared treatment as usual with the combination of treatment as usual plus cognitive behavioral social skills training . METHOD The r and omized , controlled trial included 76 middle-aged and older out patients with chronic schizophrenia , who were assigned to either treatment as usual or combined treatment . Cognitive behavioral social skills training was administered over 24 weekly group sessions . Blind raters assessed social functioning , psychotic and depressive symptoms , cognitive insight , and skill mastery . RESULTS After treatment , the patients receiving combined treatment performed social functioning activities significantly more frequently than the patients in treatment as usual , although general skill at social functioning activities did not differ significantly . Patients receiving cognitive behavioral social skills training achieved significantly greater cognitive insight , indicating more objectivity in reappraising psychotic symptoms , and demonstrated greater skill mastery . The overall group effect was not significant for symptoms , but the greater increase in cognitive insight with combined treatment was significantly correlated with greater reduction in positive symptoms . CONCLUSIONS With cognitive behavioral social skills training , middle-aged and older out patients with chronic schizophrenia learned coping skills , evaluated anomalous experiences with more objectivity ( achieved greater cognitive insight ) , and improved social functioning . Additional research is needed to determine whether cognitive insight mediates psychotic symptom change in cognitive behavior therapy for psychosis BACKGROUND Evidence for the efficacy of cognitive-behavioural therapy for schizophrenia is promising but evidence for clinical effectiveness is limited . AIMS To test the effectiveness of cognitive-behavioural therapy delivered by clinical nurse specialists in routine practice . METHOD Of 274 referrals , 66 were allocated r and omly to 9 months of treatment as usual ( TAU ) , cognitive-behavioural therapy plus TAU ( CBT ) or supportive psychotherapy plus TAU ( SPT ) and followed up for 3 months . RESULTS Treatment effects were modest but the CBT condition gave significantly greater improvement in overall symptom severity than the SPT or TAU conditions combined ( F (1,53)=4.14 ; P=0.05 ) . Both the CBT and SPT conditions combined gave significantly greater improvement in severity of delusions than did the TAU condition ( F (1,53)=4.83 ; P=0.03 ) . Clinical ly significant improvements were achieved by 7/21 in the CBT condition ( 33 % ) , 3/19 in the SPT condition ( 16 % ) and 2/17 in the TAU condition ( 12 % ) . CONCLUSIONS Cognitive-behavioural therapy delivered by clinical nurse specialists is a helpful adjunct to routine care for some people with chronic psychosis A rehabilitative coping skills module employing problem solving and cognitive behavioral therapy and an experimental repeated-measure design was tested on 55 r and omly selected persons severely h and icapped by schizophrenia , most of whom had lived almost half of their lives in psychiatric wards . Unlike the control group of 44 comparable schizophrenics , the experimental group exhibited a significant decrease in delusions and increase in self-esteem , and maintained hygiene levels BACKGROUND A series of small , mainly uncontrolled , studies have suggested that techniques adapted from cognitive-behavioural therapy ( CBT ) for depression can improve outcome in psychosis , but no large r and omised controlled trial of intensive treatment for medication-resistant symptoms of psychosis has previously been published . METHOD Sixty participants who each had at least one positive and distressing symptom of psychosis that was medication-resistant were r and omly allocated between a CBT and st and ard care condition ( n = 28 ) and a st and ard care only control condition ( n = 32 ) . Therapy was individualised , and lasted for nine months . Multiple assessment s of outcome were used . RESULTS Over nine months , improvement was significant only in the treatment group , who showed a 25 % reduction on the BPRS . No other clinical , symptomatic or functioning measure changed significantly . Participants had a low drop-out rate from therapy ( 11 % ) , and expressed high levels of satisfaction with treatment ( 80 % ) . Fifty per cent of the CBT group were treatment responders ( one person became worse ) , compared with 31 % of the control group ( three people became worse and another committed suicide ) . CONCLUSIONS CBT for psychosis can improve overall symptomatology . The findings provide evidence that even a refractory group of clients with a long history of psychosis can engage in talking about psychotic symptoms and their meaning , and this can improve outcome Cognitive Remediation Therapy ( CRT ) is a novel rehabilitation approach design ed to improve neurocognitive abilities such as attention , memory and executive functioning . The aim of the present study is to evaluate the effect of CRT on neurocognition , and secondarily on symptomatology and psychosocial functioning . Cognitive Behavioural Therapy ( CBT ) was used as a control condition because it aims to improve emotional problems and positive symptoms , focusing on modification of maladaptive beliefs and schemas , but neurocognition is not targeted . A total of 40 chronic patients with DSM-IV schizophrenia disorder were r and omly assigned for 4 months to one of two treatment groups : CRT or CBT . Repeated assessment s were conducted before and after the treatments and at the end of a follow-up period of 6 months . Additionally , a method to establish reliable change was calculated from a separate sample of 20 schizophrenic patients who were under st and ard medication without any kind of psychological treatment . Results showed that CRT produced an overall improvement on neurocognition ( Mean effect size=0.5 ) , particularly in verbal and nonverbal memory , and executive function . CBT showed the expected treatment effect on general psychopathology ( anxiety and depression ) but produced only a slight non-specific improvement in neurocognition ( Working Memory ) . Furthermore , patients receiving CRT showed improvement in social functioning , demonstrating that cognitive improvements are clinical ly meaningful . These gains were still present at the 6 month follow-up OBJECTIVE This study determined whether adding cognitive-behavioral therapy to treatment for out patients with schizophrenia would be more effective than the use of second-generation antipsychotics alone . Thirty-three patients were r and omly assigned to receive either second-generation antipsychotics alone ( N=18 ) or second-generation antipsychotics plus cognitive-behavioral therapy ( N=15 ) . METHODS All patients received pharmacotherapy from a single provider and in a predetermined st and ard manner . Psychopathology ratings were done at baseline , at the end of treatment ( 12 weeks ) and three months after completion of treatment ( 24 weeks ) . RESULTS Twenty-five ( 76 % ) patients completed baseline and 12-week evaluations , and 17 ( 68 % ) patients who finished treatment also completed evaluations at 24 weeks . At the end of treatment persons in the second-generation antipsychotics plus cognitive-behavioral therapy group were rated as having less severe delusions than patients in the group receiving second-generation antipsychotics only , and this difference was maintained three months after treatment ended . CONCLUSIONS Adding cognitive-behavioral therapy may help with reducing the severity of delusions among patients with schizophrenia BACKGROUND Little evidence exists to indicate whether community psychiatric nurses can achieve the results reported by expert cognitive-behavioural therapists in patients with schizophrenia . AIMS To assess the effectiveness and safety of a brief cognitive-behavioural therapy ( CBT ) intervention in a representative community sample of patients with schizophrenia in secondary care setting s. METHOD A pragmatic r and omised trial was performed involving 422 patients and carers to compare a brief CBT intervention against treatment as usual . RESULTS Patients who received CBT ( n=257 ) improved in overall symptomatology ( P=0.015 ; number needed to treat [NNT]=13 ) , insight ( P<0.001 ; NNT=10 ) and depression ( P=0.003 ; NNT=9 ) compared with the control group ( n=165 ) . Insight was clinical ly significantly improved ( risk ratio=1.15 , 95 % CI 1.01 - 1.31 ) . There was no increase in suicidal ideation . CONCLUSIONS Community psychiatric nurses can safely and effectively deliver a brief CBT intervention to patients with schizophrenia and their carers Clinical studies on cognitive behavioral therapy ( CBT ) that include schizophrenia patients primarily on the basis of negative symptoms are uncommon . However , those studies are necessary to assess the efficacy of CBT on negative symptoms . This article first gives an overview of CBT on negative symptoms and discusses the method ological problems of selecting an adequate control group . Furthermore , the article describes a clinical study ( the TONES- Study , IS RCT N 25455020 ) , which aims to investigate whether CBT is specifically efficacious for the reduction of negative symptoms . This multicenter r and omized clinical trial comparing CBT with cognitive remediation ( CR ) for control of nonspecific effects is depicted in detail . In our trial , schizophrenia patients ( n = 198 ) participated in manualized individual outpatient treatments . Primary outcome is the negative syndrome assessed with the positive and negative syndrome scale , analyzed with multilevel linear mixed models . Patients in both groups moderately improved regarding the primary endpoint . However , against expectation , there was no difference between the groups after treatment in the intention to treat as well as in the per- protocol analysis . In conclusion , psychotherapeutic intervention may be useful for the reduction of negative symptoms . However , there is no indication for specific effects of CBT compared with CR This is the second of two papers that present a small , r and omized control trial of cognitive behavioural therapy ( CBT ) within a group setting for the treatment of auditory hallucinations . In the previous paper , a method was described for an eight-session CBT group . Assessment s were undertaken measuring control , power , frequency , and symptoms of distress and anxiety on commencement and on completion of the group . This second paper details the experience of the group and reports on the outcomes of the assessment measures . The study concludes that group CBT was helpful in the treatment of auditory hallucinations This study aim ed at determining the effectiveness of group cognitive behavior therapy ( CBT ) for recent onset psychosis in comparison with a recognized intervention for individuals with severe mental illness – social skills training . One hundred twenty-nine participants took part in a single-blind r and omized controlled trial with repeated measures ( baseline , 3 months , and 9 months ) . Participants were r and omized to 1 of 3 conditions : group CBT , group social skills training for symptom management , or a wait-list control group . Both interventions were delivered by mental health staff with minimal training . Both treatments result ed in improvements on positive and negative symptoms compared with the wait-list control group , with the CBT group having significant effects over time on overall symptoms , and post-treatment effects on self-esteem , and active coping skills compared with the wait-list control group and lower drop-out rates than the skills training group . Therapist fidelity was adequate for both treatment conditions . Group CBT for psychosis is a promising intervention for individuals with recent onset of psychosis and their mental health professionals The experience of psychosis can lead to depression , anxiety and fear . Acceptance and Commitment Therapy ( ACT ) facilitates individuals to accept difficult mental experiences and behave in ways that are consistent with personally held values . This study was a single ( rater ) blind pilot r and omised controlled trial of ACT for emotional dysfunction following psychosis . Twenty-seven participants with psychosis were r and omised to either : ten sessions of ACT plus treatment as usual ( TAU ) or TAU alone . The Hospital Anxiety and Depression Scale , Positive and Negative Syndrome Scale , Acceptance and Action Question naire , Kentucky Inventory of Mindfulness Skills and Working Alliance Inventory were used . Individuals were assessed at baseline and 3 months post-baseline . The individuals r and omised to receive ACT found the intervention acceptable . A significantly greater proportion of the ACT group changed from being depressed at time of entry into the study to not being depressed at follow-up . The ACT group showed a significantly greater increase in mindfulness skills and reduction in negative symptoms . Results indicated that individuals r and omised to ACT had significantly fewer crisis contacts over the study . Changes in mindfulness skills correlated positively with changes in depression . ACT appears to offer promise in reducing negative symptoms , depression and crisis contacts in psychosis OBJECTIVE R and omized controlled trials have attested the efficacy of cognitive behavioral therapy ( CBT ) in reducing psychotic symptoms . Now , studies are needed to investigate its effectiveness in routine clinical practice setting s. METHOD Eighty patients with schizophrenia spectrum disorders who were seeking outpatient treatment were r and omized to a specialized cognitive behavioral intervention for psychosis ( CBTp ; n = 40 ) or a wait list ( n = 40 ) . The CBTp group was assessed at baseline , posttreatment , and 1-year follow-up . The wait list group was assessed at baseline , after a 4-month waiting period , at posttreatment , and after 1 year . The primary outcome measure was the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS The CBTp group showed significant improvement over the wait list group for the total PANSS score at posttreatment-postwaiting . CBTp was also superior to the wait list group in regard to the secondary outcomes positive symptoms , general psychopathology , depression , and functioning , but not in regard to negative symptoms . The number of dropouts during the treatment phases was low ( 11.3 % ) . Participants perceived the treatment as helpful ( 98 % ) and considered themselves improved ( 92 % ) . Significant pre- and posttreatment effect sizes varied between 0.77 for general psychopathology and 0.38 for delusional conviction . The positive effects of treatment could be maintained at 1-year follow-up , although the number of patients who had deteriorated was higher than at post assessment . CONCLUSIONS Large proportions of patients in clinical practice setting s benefit from CBTp . The efficacy of CBTp can be generalized to clinical practice despite the differences in patients , therapists , and deliverance |
12,134 | 18,318,597 | These findings support the hypothesis that alcohol intake has a marked effect on blood pressure and the risk of hypertension | BACKGROUND Alcohol has been reported to be a common and modifiable risk factor for hypertension .
However , observational studies are subject to confounding by other behavioural and sociodemographic factors , while clinical trials are difficult to implement and have limited follow-up time .
Mendelian r and omization can provide robust evidence on the nature of this association by use of a common polymorphism in aldehyde dehydrogenase 2 ( ALDH2 ) as a surrogate for measuring alcohol consumption .
ALDH2 encodes a major enzyme involved in alcohol metabolism .
Individuals homozygous for the null variant ( * 2 * 2 ) experience adverse symptoms when drinking alcohol and consequently drink considerably less alcohol than wild-type homozygotes ( * 1 * 1 ) or heterozygotes .
We hypothesise that this polymorphism may influence the risk of hypertension by affecting alcohol drinking behaviour . | Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading , despite our best efforts to improve the design and analysis of studies . Mendelian r and omization-the r and om assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures . The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies . Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian r and omization and are described . The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study , that polymorphisms may have several phenotypic effects associated with disease , the lack of suitable polymorphisms for study ing modifiable exposures of interest , and canalization-the buffering of the effects of genetic variation during development . Nevertheless , Mendelian r and omization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to underst and ing and preventing the adverse effects on human health of modifiable exposures BACKGROUND Epidemiologic studies have shown alcohol consumption to be inversely as well as positively related to body weight and body fat . Metabolic studies have shown an increase in energy intake as well as compensation after alcohol consumption . OBJECTIVE Our objective was to assess the effects on energy intake of an apéritif compared with those of a water appetizer and 3 fruit juice appetizers . DESIGN Fifty-two men and women aged 20 - 45 y with a body mass index ( in kg/m2 ) between 20 and 32 were r and omly given 1 MJ ( 340 mL ) alcohol ( wine or beer ) , fat ( cream fruit juice ) , protein ( protein fruit juice ) , carbohydrate ( grape juice ) , or water , or no preload 30 min before an ad libitum lunch consumed from the universal eating monitor . RESULTS Energy intake ( 3.5+/-0.3 MJ compared with 2.7+/-0.2 MJ , P < 0.001 ) and eating rate were higher ( 44+/-3 g/min compared with 38+/-3 g/min , P < 0.01 ) , meal duration was longer ( 14 min compared with 12.0 min , P < 0.01 ) , satiation started to increase later ( 3.5 min compared with 1.5 min , P < 0.01 ) , and eating was prolonged after maximum satiation ( 2.5 min compared with 0.6 min , P < 0.01 ) after an apéritif than after a fat , protein , or carbohydrate appetizer , . Twenty-four-hour energy intake was higher on a day that an apéritif was consumed than after water or no preload . CONCLUSION Twenty-four-hour energy intake was elevated with a 1-MJ apéritif but not with a 1-MJ liquid carbohydrate , fat , or protein appetizer The vasodilation that follows acute alcohol intake is hard to conciliate with the high prevalence of hypertension detected in those persons who consume regular amounts of alcohol . In this experiment we examined early and late hemodynamic effects of acute administration of water and of 15 g , 30 g , and 60 g of alcohol in 40 normal men , aged 19 to 30 years , using 24-h ambulatory blood pressure monitoring ( ABPM ) . Mean systolic and diastolic blood pressures were each approximately 4 mm Hg lower during the period immediately after ingestion of 60 g ( v 0 g ) of ethanol , and were 7 and 4 mm Hg higher , respectively , at night . The day minus night differences displayed a dose-response curve both for systolic ( P < .001 ) and diastolic blood pressure ( P = .045 ) . Three subjects in the 60-g group had more than 50 % of nightly blood pressure loads in the hypertensive range against none in the remaining groups ( P < .01 ) . In conclusion , our findings suggest that acute alcohol intake elicits a biphasic hemodynamic response , causing , first , vasodilatation and , later , a pressor effect . The higher prevalence of hypertension in alcohol abusers seen in epidemiological surveys may be , in part , a result of measurements done in the period of transiently increased blood pressure during ethanol washout Objective —Nitrates are used widely in clinical practice . However , the mechanism underlying the bioactivation of nitrates to release NO remains unclear . Recent animal data suggest that mitochondrial aldehyde dehydrogenase ( ALDH2 ) plays a central role in nitrate bioactivation , but its role in humans is not known . We investigated the role of ALDH2 in the vascular effects of nitroglycerin ( NTG ) in humans in vivo . Methods and Results —Forearm blood flow ( FBF ) responses to intra-arterial infusions of NTG , sodium nitroprusside ( SNP ) , and verapamil were measured in 12 healthy volunteers before and after ALDH2 inhibition by disulfiram . All drugs caused a dose-dependent vasodilatation . However , only the response to NTG was significantly reduced after disulfiram therapy ( 33 % reduction in area under the curve [ AUC ] ; P=0.002 ) . Separately , 11 subjects of East Asian origin , with the loss-of-function glu504lys mutation in the ALDH2 gene , received intra-arterial NTG , SNP , and verapamil . Only the FBF response to NTG was lower in the volunteers with the glu504lys mutation compared with East Asian and non-Asian wild-type control subjects ( 40 % reduction in AUC ; P=0.02 ) . Conclusions —The findings suggest that ALDH2 is involved in the bioactivation of NTG in humans in vivo but accounts for less than half of the total bioactivation . This may be of clinical importance in patients with mutations in the ALDH2 gene and in those taking drugs that inhibit ALDH2 Abstract Deficiencies in mitochondrial low-Km aldehyde dehydrogenase ( ALDH2 ) activity , and consequently high blood acetaldehyde levels , have been suggested to relate to various diseases in Japanese , including esophageal cancer . In the present study , 200 men aged 35 - 59 years r and omly selected from an occupational population were analyzed for the association of ALDH2 genotypes and cytochrome P450 - 2E1 ( CYP2E1 ) genotypes with the urinary excretion of acetaldehyde ( which is bound to some chemicals in the urine ) and with common alcohol-related health consequences . Urinary acetaldehyde excretion was increased , reflecting increased alcohol consumption even in this moderate alcohol-consuming population . Neither the ALDH2 nor the CYP2E1 genotypes showed significant influence on the elevation of urinary acetaldehyde excretion . Neither these genotypes nor urinary acetaldehyde concentration significantly affected blood pressure , serum aspartate aminotransferase and gamma-glutamyl transferase activities , or serum HDL-cholesterol and lipid peroxide concentrations . It was concluded that acetaldehyde accumulates in moderate alcohol consumers irrespective of ALDH2 and CYP2E1 genotype , and that the implication s of these genotypes and acetaldehyde accumulation in terms of common alcohol-related health consequences were obscure . The results also suggest that the carcinogenicity of acetaldehyde on esophageal mucosa depends greatly upon repeated exposure to high blood acetaldehyde , even through transient rather than chronic exposure Among older people , the detection and control of hypertension is particularly important to reduce cardiovascular disease risk . This cross-sectional survey aim ed to describe the detection , treatment and control of hypertension in older British adults . A total of 3059 women and 3007 men aged 60–79 years were r and omly selected from general practice age/sex registers in 24 British towns and examined from 1998 to 2001 . Of these , 52.6 % women and 47.9 % men had at least one indicator of hypertension ( high blood pressure on examination , or taking antihypertensive medication or recalled a doctor diagnosis of high blood pressure ) . Among women , 50 % of those with any indication of hypertension were on treatment and 29 % were well controlled , and among men 45 % were on treatment and 16 % were well controlled . With the exception of alcohol use in men ( adjusted odds ratio 0.67 ( 0.46 , 0.98 ) ) , socioeconomic factors , area of residence and behavioural risk factors were not associated with good control among those with hypertension in either sex . Of those on treatment , 20.7 % of women and 28 % of men were on two classes of antihypertensive medication and 3.5 and 4.9 % , respectively , were on three or more classes of antihypertensive medication . Among those with a doctor diagnosis of hypertension and taking antihypertensive medication , the proportion with well controlled blood pressure did not differ between those on more than one antihypertensive and those on just one in either sex . We conclude that targets of good control are rarely met in older individuals , who would benefit from the associated reduction in cardiovascular disease risk OBJECTIVE Alcohol consumption may play a role in the development of obesity but the relationship between alcohol and weight is still unclear . The aim of our study was to assess the cross-sectional association of intakes of total alcohol and of specific alcoholic beverages ( wine , beer and spirits ) with waist-to-hip ratio ( WHR ) and body mass index ( BMI ) in a large sample of adults from all over France . DESIGN Cross-sectional . SETTING Participants were free-living healthy volunteers of the SU.VI.MAX study ( an intervention study on the effects of antioxidant supplementation on chronic diseases ) . SUBJECTS For 1481 women aged 35 - 60 years and 1210 men aged 45 - 60 years , intakes of total alcohol and specific alcoholic beverages were assessed by six 24-hour dietary records . BMI and WHR were measured during a clinical examination the year after . RESULTS A J-shaped relationship was found between total alcohol consumption and WHR in both sexes and between total alcohol consumption and BMI in men only ( P<0.05 ) . The same relationships were observed with wine ( P<0.05 ) ; men and women consuming less than 100 g day(-1 ) had a lower BMI ( men only ) and WHR than non-drinkers or those consuming more . Spirits consumption was positively associated with BMI ( linear regression coefficient beta=0.21 , 95 % confidence interval ( CI ) : 0.09 - 0.34 and beta=0.22 , 95 % CI : 0.06 - 0.39 for men and women , respectively ) and WHR ( beta=0.003 , 95 % CI : 0.001 - 0.005 and beta=0.003 , 95%CI : 0.0002 - 0.006 ) in both sexes in a linear fashion . No relationship between beer consumption and BMI or WHR was found . CONCLUSION If confirmed in longitudinal studies , our results indicate that consumption of alcoholic beverages may be a risk factor for obesity BACKGROUND Extract of globe artichoke ( Cynara scolymus ) is promoted as a possible preventive or cure for alcohol-induced hangover symptoms . However , few rigorous clinical trials have assessed the effects of artichoke extract , and none has examined the effects in relation to hangovers . We undertook this study to test whether artichoke extract is effective in preventing the signs and symptoms of alcohol-induced hangover . METHODS We recruited healthy adult volunteers between 18 and 65 years of age to participate in a r and omized double-blind crossover trial . Participants received either 3 capsules of commercially available st and ardized artichoke extract or indistinguishable , inert placebo capsules immediately before and after alcohol exposure . After a 1-week washout period the volunteers received the opposite treatment . Participants predefined the type and amount of alcoholic beverage that would give them a hangover and ate the same meal before commencing alcohol consumption on the 2 study days . The primary outcome measure was the difference in hangover severity scores between the artichoke extract and placebo interventions . Secondary outcome measures were differences between the interventions in scores using a mood profile question naire and cognitive performance tests administered 1 hour before and 10 hours after alcohol exposure . RESULTS Fifteen volunteers participated in the study . The mean number ( and st and ard deviation ) of alcohol units ( each unit being 7.9 g , or 10 mL , of ethanol ) consumed during treatment with artichoke extract and placebo was 10.7 ( 3.1 ) and 10.5 ( 2.4 ) respectively , equivalent to 1.2 ( 0.3 ) and 1.2 ( 0.2 ) g of alcohol per kilogram body weight . The volume of nonalcoholic drink consumed and the duration of sleep were similar during the artichoke extract and placebo interventions . None of the outcome measures differed significantly between interventions . Adverse events were rare and were mild and transient . INTERPRETATION Our results suggest that artichoke extract is not effective in preventing the signs and symptoms of alcohol-induced hangover . Larger studies are required to confirm these findings Blood pressure , heart rate and responses to a range of autonomic reflex tests were studied in 10 normotensive male volunteers following 7 days of regular alcohol consumption ( 0.8 g/kg per day ) or 7 days of abstaining from alcohol in a crossed , r and om order , open study . Systolic and diastolic pressures were significantly higher following alcohol intake than the alcohol-free control period ( mean rise of 3.0 mmHg systolic and 3.1 mmHg diastolic , P less than 0.05 and P less than 0.01 , respectively ) . Regular alcohol consumption attenuated the rise in blood pressure during isometric exercise and h and immersion in ice water , but did not affect blood pressure or heart rate responses to bicycle exercise . Resting , supine plasma noradrenaline levels , increases in noradrenaline levels during sympathetic activation and vagal reflexes ( st and ing to lying test , diving reflex and Valsalva manoeuvre ) did not differ significantly between the alcohol and control phases of the study . These findings support previous evidence that regular alcohol consumption decreases adrenoceptor mediated cardiovascular reactivity . However , the relationship between this effect and the rise in blood pressure that follows regular , moderate alcohol consumption remains unclear Context Heavy alcohol consumption may increase risk for hypertension , but does it increase risk for cardiovascular disease ? Contributions In this 16-year prospect i ve study , 11711 male health professionals with hypertension reported their average alcohol consumption every 4 years . Compared with men who abstained from alcohol , men who consumed 10 to 14 g/d ( about 1 drink per day ) , 15 to 29 g/d , 30 to 49 g/d , and more than 49 g/d of alcohol had decreased risk for myocardial infa rct ion . Alcohol intake seemed unrelated to total death or death due to cardiovascular disease . Caution s Alcohol intake and hypertension were self-reported . Few outcomes limited ability to determine precise relationships between alcohol and stroke . The Editors Hypertension is a major public health burden in the United States . In 1999 , 65 million adults had the condition , an approximately 30 % increase from 1991 ( 1 ) . Hypertension is associated with a doubled risk for cardiovascular disease ( CVD ) and may account for 30 % of events associated with CVD ( 2 ) . Moderate alcohol consumption is inversely associated with CVD and total death ( 3 , 4 ) . However , intake of more than 30 grams of alcohol ( that is , more than 2 drinks ) per day is associated with an increased risk for hypertension ( 5 , 6 ) . Guidelines for alcohol consumption among patients with hypertension range from a limit of 2 to 3 drinks per day to complete abstention from alcohol ( 79 ) . These contradictory recommendations may reflect the paucity of information on the relation between alcohol consumption and risk for CVD among patients with hypertension . To our knowledge , only 3 studies have addressed the relationship of alcohol intake and death due to CVD among patients with hypertension ( 1012 ) . Although the studies reported lower numbers of death due to CVD with moderate alcohol consumption , none assessed specific incidence of MI . Of importance , the studies were limited to alcohol consumption assessed after diagnosis of hypertension and were unable to account for changes of alcohol consumption after the diagnosis . To address these issues , we investigated whether alcohol consumption is inversely associated with CVD and death among 11711 men with hypertension participating in the Health Professionals Follow-Up Study ( HPFS ) , a prospect i ve cohort of male health professionals in the United States . Methods The HPFS enrolled 51529 male dentists , veterinarians , optometrists , pharmacists , osteopathic physicians , and podiatrists from the United States who were 40 to 75 years of age and who returned a mailed question naire about diet and medical history in 1986 . Follow-up question naires were sent biennially to up date information on exposures and newly diagnosed illnesses . Hypertensive status was determined from the biennial question naires . In 1986 , participants were asked if they had ever been diagnosed with hypertension and , if so , when . On subsequent question naires , participants reported whether they had been diagnosed with hypertension in the past 2 years and , if so , the year of diagnosis . For this analysis , we included 9016 men with hypertension whose condition was diagnosed during follow-up ( that is , men with incident hypertension ) and 2695 men with hypertension at baseline whose condition was diagnosed between 1975 and 1986 and who reported not changing their alcohol consumption during that time ( that is , men with prevalent hypertension ) . From the full cohort of 51529 men , we excluded 4397 who reported a baseline history of cardiovascular disease , stroke , or cancer ( other than nonmelanoma skin cancer ) ; 81 with hypertension diagnosed after a CVD event ; 1653 who had missing or implausible nutritional information at baseline ( including missing alcohol consumption,70 missing food items , or estimated daily energy intake 800 or 4200 kcal [ only 438 of these participants were actually hypertensive ] ) ; 271 with missing information for smoking , physical activity , or body mass index ( BMI ) ; and 95 whose initial question naire had other technical problems . We also excluded 6548 men at baseline because we could not determine their drinking history , because hypertension was diagnosed before 1975 , or because they reported substantially changing their alcohol consumption within 10 years before enrollment . Of the remaining men , we identified 11711 patients with hypertension at baseline or during follow-up who were eligible for analysis . Although our sample size was set by the size of the original HPFS cohort assembled in 1986 , a sample size calculation showed that 1700 participants in the abstaining and moderate-drinking categories would detect a relative risk of 0.6 , as observed by Malinski and colleagues ( 10 ) , with 80 % power and accepting a false-positive rate of 0.05 . We assessed alcohol consumption by using a 131-item semiquantitative food-frequency question naire with separate items for beer , white wine , red wine , and liquor . We specified st and ard portions as a glass , bottle , or can of beer ; a 4-ounce glass of wine ; and a shot of liquor . For each beverage , participants were asked how often on average over the past year they consumed that amount . We calculated ethanol intake by multiplying the frequency of consumption of each beverage by the alcohol content of the specified portion size ( 12.8 g for beer , 11.0 g for wine , and 14.0 g for liquor ) and summing across beverages ( 13 ) . This process was repeated for the years 1990 , 1994 , and 1998 , with an added item about light beer in 1994 . In 1986 , men also reported the number of days per week that they typically drank any form of alcohol . We examined associations between alcohol consumption estimated by using the food-frequency question naire with consumption estimated by using 2 one-week dietary records collected approximately 6 months apart from 136 participants residing in eastern Massachusetts ( 14 , 15 ) . The Spearman correlation coefficient between these 2 measures was 0.86 . Estimated mean alcohol intake was 12.8 grams per day using dietary records and 12.5 grams per day using the food-frequency question naire , with no evidence of systematic bias . The correlation coefficient for drinking frequency between our question naire and diet records was 0.79 . Outcomes and Measurements Our primary end points were incident nonfatal MI and fatal coronary heart disease or stroke . Myocardial infa rct ion and stroke were first identified by self-reports on biennial question naires and then confirmed by medical records with World Health Organization or National Survey of Stroke criteria ( 16 ) . Fatal MI and stroke were confirmed by medical records or autopsy reports . All end points were confirmed by a physician blinded to exposure status . Approximately 80 % of participants had MI that was considered definite ; the remaining patients had MI that was considered probable and were excluded as end points in sensitivity analyses . Further details of the confirmation of end points are published elsewhere ( 17 , 18 ) . Other end points were total death ; death due to CVD ; and death augmented by alcohol intake , including cirrhosis , alcohol-related types of cancer , accidents and other external causes , cancer of the colon and rectum , pneumonia , and hemorrhagic stroke according to Thun and colleagues ( 19 ) . Covariate information was derived from biennial question naires . Nutritional information was derived from food-frequency question naires . Participants self-reported cardiovascular risk factors ( self-report of physician-diagnosed diabetes and hypercholesterolemia , cigarette smoking , physical activity , and weight ) every 2 years . Aspirin use included use of aspirin and aspirin-containing products at least twice weekly . Regular use of lipid-lowering therapy and several categories of antihypertensive medication ( for example , diuretics , -blockers , calcium-channel blockers , and -blockers ) was also recorded biennially . Nutritional variables , anthropomorphic measures , aspirin use , and self-reported CVD risk factors have been vali date d ( 2025 ) . We calculated person-years of follow-up from the date of return of the 1986 question naire ( for men with hypertension at baseline ) or date of diagnosis of hypertension ( for incident cases of hypertension ) to the date of the first CVD event , the date of death , or 31 January 2002 . We used Cox proportional hazards models with time-varying covariates to estimate hazard ratios for categories of alcohol intake relative to abstainers ( 26 ) . We simultaneously controlled for age ; smoking ( never , former , 1 to 14 cigarettes per day , 15 to 24 cigarettes per day , and 25 cigarettes per day ) ; BMI ( in quintiles ) ; diabetes ; hypercholesterolemia ; parental history of MI ; aspirin use ; lipid-lowering therapy ; 5 categories of leisure-time physical activity ; quintiles of energy intake ; and quintiles of energy-adjusted intake of saturated fat , trans fatty acids , folate , vitamin E , magnesium , sodium , potassium , -3 fatty acids , and dietary fiber . Alcohol consumption and dietary variables were up date d every 4 years ; other potential confounders were up date d every 2 years . We stopped updating participants alcohol use if they developed cancer ( other than nonmelanoma skin cancer ) for all analyses . In secondary analyses for coronary heart disease outcomes , we censored participants when they developed cancer . To examine possible confounding by sociodemographic status , we adjusted for marital and employment status ( full-time , part-time , or retired ) , profession , and ethnicity in the multivariate model . We conducted tests of linear trend across categories of increasing alcohol consumption by treating the midpoints of consumption in categories as a continuous variable . The possibility of a nonlinear relation between alcohol consumption and risk for MI was examined with restricted cubic splines ( 27 ) and tested with the likelihood ratio test , comparing models with only the linear term to models with linear and cubic spline terms . None of the nonlinear models provided a statistically significantly better model-fit than |
12,135 | 29,615,442 | The cost-effectiveness evidence for CVD and DM interventions in South Asia is growing , but most evidence is from India and limited to decision modelled outcomes . | OBJECTIVES More than 80 % of cardiovascular diseases ( CVD ) and diabetes mellitus ( DM ) burden now lies in low and middle-income countries .
Hence , there is an urgent need to identify and implement the most cost-effective interventions , particularly in the re source -constraint South Asian setting s. Thus , we aim ed to systematic ally review the cost-effectiveness of individual-level , group-level and population -level interventions to control CVD and DM in South Asia . | Background — Evidence on economically efficient strategies to lower blood pressure ( BP ) from low- and middle-income countries remains scarce . The Control of Blood Pressure and Risk Attenuation ( COBRA ) trial r and omized 1341 hypertensive subjects in 12 r and omly selected communities in Karachi , Pakistan , to 3 intervention programs : ( 1 ) combined home health education ( HHE ) plus trained general practitioner ( GP ) ; ( 2 ) HHE only ; and ( 3 ) trained GP only . The comparator was no intervention ( or usual care ) . The reduction in BP was most pronounced in the combined group . The present study examined the cost-effectiveness of these strategies . Methods and Results — Total costs were assessed at baseline and 2 years to estimate incremental cost-effectiveness ratios based on ( 1 ) intervention cost ; ( 2 ) cost of physician consultation , medications , diagnostics , changes in lifestyle , and productivity loss ; and ( 3 ) change in systolic BP . Precision of the incremental cost-effectiveness ratio estimates was assessed by 1000 bootstrapping replications . Bayesian probabilistic sensitivity analysis was also performed . The annual costs per participant associated with the combined HHE plus trained GP , HHE alone , and trained GP alone were $ 3.99 , $ 3.34 , and $ 0.65 , respectively . HHE plus trained GP was the most cost-effective intervention , with an incremental cost-effectiveness ratio of $ 23 ( 95 confidence interval , 6–99 ) per mm Hg reduction in systolic BP compared with usual care , and remained so in 97.7 of 1000 bootstrapped replications . Conclusions — The combined intervention of HHE plus trained GP is potentially affordable and more cost-effective for BP control than usual care or either strategy alone in some communities in Pakistan , and possibly other countries in Indochina with similar healthcare infrastructure . Clinical Trial Registration — http://www . clinical trials.gov . Unique identifier : NCT00327574 Objective : To estimate and compare the cost-effectiveness and safety of nebivolol with sustained-release metoprolol in reducing blood pressure by 1 mm of Hg per day in hypertensive patients . Material s and Methods : This was a prospect i ve , r and omized , open label , observational analysis of cost-effectiveness , in a question naire-based fashion to compare the cost of nebivolol ( 2.5 mg , 5 mg , 10 mg ) and sustained released metoprolol succinate ( 25 mg , 50 mg , 100 mg ) in hypertensive patients using either of the two drugs . A total of 60 newly detected drug naïve hypertensive patients were considered for the comparison , of which 30 patients were prescribed nebivolol and the other 30 were prescribed metoprolol succinate as per the recommended dosage . Based on the data , statistical analysis was carried out using GraphPad Prism 5 and MS Excel Spreadsheet 2007 . Result : The cost of reducing 1 mm of Hg blood pressure per day with nebivolol was 0.60 , 0.70 , and 1.06 INR , whereas that of metoprolol succinate was 0.93 , 1.18 , and 1.25 INR at their respective equivalent doses , hence significantly lower with the nebivolol group as compared to the metoprolol group ( P < 0.05 ) . Conclusion : This pharmacoeconomic analysis shows that nebivolol is more cost-effective as compared to metoprolol when the cost per reduction in blood pressure per day is considered . This may affect the patients economically during their long-term use of these molecules for the treatment of hypertension Introduction While a number of strategies are being implemented to control cardiovascular diseases ( CVDs ) and type 2 diabetes mellitus ( T2DM ) , the cost-effectiveness of these in the South Asian context has not been systematic ally evaluated . We aim to systematic ally review the economic ( cost-effectiveness ) evidence available on the individual- , group- and population -level interventions for control of CVD and T2DM in South Asia . Methods and analysis This review will consider all relevant economic evaluations , either conducted alongside r and omised controlled trials or based on decision modelling estimates . These studies must include participants at risk of developing CVD/T2DM or with established disease in one or more of the South Asian countries ( India , Bangladesh , Pakistan , Sri Lanka , Nepal , Maldives , Bhutan and Afghanistan ) . We will identify relevant papers by systematic ally search ing all major data bases and registries . Selected articles will be screened by two independent research ers . Method ological quality of the studies will be assessed using a modified Drummond and a Phillips checklist . Cochrane guidelines will be followed for bias assessment in the effectiveness studies . Results Results will be presented in line with the PRISMA ( Preferred Reporting Items for Systematic review and Meta- analysis ) checklist , and overall quality of evidence will be presented as per the GRADE ( Grade s of Recommendation , Assessment , Development and Evaluation ) approach . Ethics and dissemination The study has received ethics approval from the All India Institute of Medical Sciences , New Delhi , India . The results of this review will provide policy-relevant recommendations for the uptake of cost-effectiveness evidence in prioritising decisions on essential chronic disease care packages for South Asia . Study registration number PROSPERO CRD42013006479 Background Like a growing number of rapidly developing countries , India has begun to develop a system for large-scale community-based screening for diabetes . We sought to identify the implication s of using alternative screening instruments to detect people with undiagnosed type 2 diabetes among diverse population s across India . Methods and Findings We developed and vali date d a microsimulation model that incorporated data from 58 studies from across the country into a nationally representative sample of Indians aged 25–65 y old . We estimated the diagnostic and health system implication s of three major survey-based screening instruments and r and om glucometer-based screening . Of the 567 million Indians eligible for screening , depending on which of four screening approaches is utilized , between 158 and 306 million would be expected to screen as “ high risk ” for type 2 diabetes , and be referred for confirmatory testing . Between 26 million and 37 million of these people would be expected to meet international diagnostic criteria for diabetes , but between 126 million and 273 million would be “ false positives . ” The ratio of false positives to true positives varied from 3.9 ( when using r and om glucose screening ) to 8.2 ( when using a survey-based screening instrument ) in our model . The cost per case found would be expected to be from US$ 5.28 ( when using r and om glucose screening ) to US$ 17.06 ( when using a survey-based screening instrument ) , presenting a total cost of between US$ 169 and US$ 567 million . The major limitation of our analysis is its dependence on published cohort studies that are unlikely fully to capture the poorest and most rural areas of the country . Because these areas are thought to have the lowest diabetes prevalence , this may result in overestimation of the efficacy and health benefits of screening . Conclusions Large-scale community-based screening is anticipated to produce a large number of false-positive results , particularly if using currently available survey-based screening instruments . Re source allocators should consider the health system burden of screening and confirmatory testing when instituting large-scale community-based screening for diabetes Abstract Aims : The aim of this analysis was to assess the cost-effectiveness of switching from biphasic human insulin 30 ( BHI ) , insulin glargine ( IGlar ) , or neutral protamine Hagedorn ( NPH ) insulin ( all ± oral glucose-lowering drugs [ OGLDs ] ) to biphasic insulin aspart 30 ( BIAsp 30 ) in people with type 2 diabetes in India , Indonesia , and Saudi Arabia . Methods : The IMS CORE Diabetes Model was used to determine the clinical outcome , costs , and cost-effectiveness of switching from treatment with BHI , IGlar , or NPH to BIAsp 30 over a 30-year time horizon . A 1-year analysis was also performed based on quality -of-life data and treatment costs . Incremental cost-effectiveness ratios ( ICERs ) were expressed as a fraction of gross domestic product ( GDP ) per capita , and cost-effectiveness was defined as ICER < 3-times GDP per capita . Results : Switching treatment from BHI , IGlar , or NPH to BIAsp 30 was associated with an increase in life expectancy of > 0.7 years , reduction in all diabetes-related complications , and was considered as cost-effective or highly cost-effective in India , Indonesia , and Saudi Arabia ( BHI to BIAsp 30 , 0.26 in India , 1.25 in Indonesia , 0.01 in Saudi Arabia ; IGlar to BIAsp 30 , −0.68 in India , −0.21 in Saudi Arabia ; NPH to BIAsp 30 , 0.15 in India , −0.07 in Saudi Arabia ; GDP per head per annum/ quality -adjusted life-year ) . Cost-effectiveness was maintained in the 1-year analyses . Conclusions : Switching from treatment with BHI , IGlar , or NPH to BIAsp 30 ( all ± OGLDs ) was found to be cost-effective in India , Indonesia , and Saudi Arabia , both in the long and short term OBJECTIVE Intervention strategies are available for reducing the high global burden of hazardous alcohol use as a risk factor for disease , but little is known about their potential costs and effects at a population level . This study set out to estimate these costs and effects . METHOD Analyses were carried out for 12 epidemiological World Health Organization subregions of the world . A population model was used to estimate the impact of evidence -based personal and nonpersonal interventions --including brief physician advice , taxation , roadside r and om breath testing , restricted sales access and advertising bans . Costs were measured in international dollars ( I$ ) ; population -level intervention effects were gauged in terms of disability-adjusted life years ( DALYs ) averted . Average and incremental cost-effectiveness ratios ( CERs ) were computed . RESULTS The most costly interventions to implement are brief advice in primary care and roadside breath testing of drivers . In population s with a high prevalence of heavy drinkers ( more than 5 % , such as Europe and North America ) , the most effective and cost-effective intervention was taxation ( more than 500 DALYs averted per 1 million population ; CER < I$500 per DALY averted ) . In population s with a lower prevalence of heavy drinking , however , taxation is estimated to be less cost effective overall than other , more targeted strategies , such as brief physician advice , roadside breath testing and advertising bans . CONCLUSIONS The most efficient public health response to the burden of alcohol use depends on the prevalence of hazardous alcohol use , which is related to overall per capita consumption . Population -wide measures , such as taxation , are expected to represent the most cost-effective response in population s with moderate or high levels of drinking , whereas more targeted strategies are indicated in population s with lower rates of hazardous alcohol use OBJECTIVES Mathematical modeling is used widely in economic evaluations of pharmaceuticals and other health-care technologies . Users of models in government and the private sector need to be able to evaluate the quality of models according to scientific criteria of good practice . This report describes the consensus of a task force convened to provide modelers with guidelines for conducting and reporting modeling studies . METHODS The task force was appointed with the advice and consent of the Board of Directors of ISPOR . Members were experienced developers or users of models , worked in academia and industry , and came from several countries in North America and Europe . The task force met on three occasions , conducted frequent correspondence and exchanges of drafts by electronic mail , and solicited comments on three drafts from a core group of external review ers and more broadly from the membership of ISPOR . RESULTS Criteria for assessing the quality of models fell into three areas : model structure , data used as inputs to models , and model validation . Several major themes cut across these areas . Models and their results should be represented as aids to decision making , not as statements of scientific fact ; therefore , it is inappropriate to dem and that models be vali date d prospect ively before use . However , model assumptions regarding causal structure and parameter estimates should be continually assessed against data , and models should be revised accordingly . Structural assumptions and parameter estimates should be reported clearly and explicitly , and opportunities for users to appreciate the conditional relationship between inputs and outputs should be provided through sensitivity analyses . CONCLUSIONS Model-based evaluations are a valuable re source for health-care decision makers . It is the responsibility of model developers to conduct modeling studies according to the best practicable st and ards of quality and to communicate results with adequate disclosure of assumptions and with the caveat that conclusions are conditional upon the assumptions and data on which the model is built Background R and omized control trials from the developed world report that clinical decision support systems ( DSS ) could provide an effective means to improve the management of hypertension ( HTN ) . However , evidence from developing countries in this regard is rather limited , and there is a need to assess the impact of a clinical DSS on managing HTN in primary health care center ( PHC ) setting s. Methods and Results We performed a cluster r and omized trial to test the effectiveness and cost‐effectiveness of a clinical DSS among Indian adult hypertensive patients ( between 35 and 64 years of age ) , wherein 16 PHC clusters from a district of Telangana state , India , were r and omized to receive either a DSS or a chart‐based support ( CBS ) system . Each intervention arm had 8 PHC clusters , with a mean of 102 hypertensive patients per cluster ( n=845 in DSS and 783 in CBS groups ) . Mean change in systolic blood pressure ( SBP ) from baseline to 12 months was the primary endpoint . The mean difference in SBP change from baseline between the DSS and CBS at the 12th month of follow‐up , adjusted for age , sex , height , waist , body mass index , alcohol consumption , vegetable intake , pickle intake , and baseline differences in blood pressure , was −6.59 mm Hg ( 95 % confidence interval : −12.18 to −1.42 ; P=0.021 ) . The cost‐effective ratio for CBS and DSS groups was $ 96.01 and $ 36.57 per mm of SBP reduction , respectively . Conclusion Clinical DSS are effective and cost‐effective in the management of HTN in re source ‐constrained PHC setting s. Clinical Trial Registration URL : http://www.ctri.nic.in . Unique identifier : CTRI/2012/03/002476 Background We performed a prospect i ve , r and omized trial comparing percutaneous balloon commissurotomy with surgical closed commissurotomy in 40 patients with severe rheumatic mitral stenosis . Methods and Results Data were analyzed by investigators who were masked to treatment assignment or phase of study . Patients r and omized to balloon ( n = 20 ) or surgical ( n = 20 ) commissurotomy had severe mitral stenosis without significant baseline differences ( left atrial pressure , 26.1±4.2 versus 27.6 + 6.2 mm Hg ; mitral valve gradient , 18.0±4.2 versus 19.7±6.3 mm Hg ; mitral valve area , 1.0±0.2 versus 1.0±0.4 cm2 , respectively ) . At 1-week follow-up after balloon commissurotomy , pulmonary wedge pressure was 14.3 ± 7.2 mm Hg ; mitral valve gradient was 9.6 ± 5.1 mm Hg ; and mitral valve area was 1.6±0.6 cm2 ( all p < 0.0001 ) . At 1-week follow-up after surgical closed commissurotomy , wedge pressure was 13.7 ± 5.4 mm Hg ; mitral valve gradient was 9.4±4.2 mm Hg ( both p < 0.0001 ) ; and mitral valve area was 1.6±0.7 cm2 ( p < 0.003 ) . At 8-month follow-up , improvement occurred in both groups : Mitral valve area was 1.6±0.6 cm2 in the balloon commissurotomy group ( p < 0.002 ) and was 1.8±0.6 cm2 in the surgical closed commissurotomy group ( p < 0.0001 ) . There was no difference between the groups at 1-week or 8-month follow-up ( all p>0.4 ) . One case of severe mitral regurgitation occurred in each group ; complications were otherwise related to transseptal catheterization . There was no death , stroke , or myocardial infa rct ion . Cost analysis revealed that balloon commissurotomy may substantially exceed the cost of surgical commissurotomy in developing countries , whereas it may represent a significant savings in industrialized nations . Conclusions We conclude that percutaneous balloon commissurotomy and surgical closed commissurotomy result in comparable hemodynamic improvement that is sustained through 8 months of follow-up Abstract Objective : To determine whether tight control of blood pressure prevents macrovascular and microvascular complications in patients with type 2 diabetes . Design : R and omised controlled trial comparing tight control of blood pressure aim ing at a blood pressure of < 150/85 mm Hg ( with the use of an angiotensin converting enzyme inhibitor captopril or a β blocker atenolol as main treatment ) with less tight control aim ing at a blood pressure of < 180/105 mm Hg . Setting : 20 hospital based clinics in Engl and , Scotl and , and Northern Irel and . Subjects : 1148 hypertensive patients with type 2 diabetes ( mean age 56 , mean blood pressure at entry 160/94 mm Hg ) ; 758 patients were allocated to tight control of blood pressure and 390 patients to less tight control with a median follow up of 8.4 years . Main outcome measures : Predefined clinical end points , fatal and non-fatal , related to diabetes , deaths related to diabetes , and all cause mortality . Surrogate measures of microvascular disease included urinary albumin excretion and retinal photography . Results : Mean blood pressure during follow up was significantly reduced in the group assigned tight blood pressure control ( 144/82 mm Hg ) compared with the group assigned to less tight control ( 154/87 mm Hg ) ( P<0.0001 ) . Reductions in risk in the group assigned to tight control compared with that assigned to less tight control were 24 % in diabetes related end points ( 95 % confidence interval 8 % to 38 % ) ( P=0.0046 ) , 32 % in deaths related to diabetes ( 6 % to 51 % ) ( P=0.019 ) , 44 % in strokes ( 11 % to 65 % ) ( P=0.013 ) , and 37 % in microvascular end points ( 11 % to 56 % ) ( P=0.0092 ) , predominantly owing to a reduced risk of retinal photocoagulation . There was a non-significant reduction in all cause mortality . After nine years of follow up the group assigned to tight blood pressure control also had a 34 % reduction in risk in the proportion of patients with deterioration of retinopathy by two steps ( 99 % confidence interval 11 % to 50 % ) ( P=0.0004 ) and a 47 % reduced risk ( 7 % to 70 % ) ( P=0.004 ) of deterioration in visual acuity by three lines of the early treatment of diabetic retinopathy study ( ETDRS ) chart . After nine years of follow up 29 % of patients in the group assigned to tight control required three or more treatments to lower blood pressure to achieve target blood pressures . Conclusion : Tight blood pressure control in patients with hypertension and type 2 diabetes achieves a clinical ly important reduction in the risk of deaths related to diabetes , complications related to diabetes , progression of diabetic retinopathy , and deterioration in visual acuity OBJECTIVE To compare the efficacy , safety , cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients . PATIENTS AND METHODS Ninety-three patients with unstable angina were r and omized to receive either unfractionated heparin ( UFH ) or enoxaparin in an open design clinical trial with blinded end point evaluation . The effects of the heparins on platelet aggregation were also compared . RESULTS The composite end point of myocardial infa rct ion , cardiac death , recurrent angina and need for intervention was observed in 62 % of patients treated with UFH and in 37 % of patients treated with enoxaparin ( RR 1.7 , 95 % CI 0.75 to 3.71 , p = 0.04 ) . There was no difference in the frequency or severity of adverse events . A cost-effectiveness analysis showed both the heparins to be similar . Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin . CONCLUSIONS Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety . No difference in costs was detected in this study . The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH BACKGROUND Comparative data for efficacy and safety between various low-molecular-weight heparins ( LMWHs ) in patients with unstable angina is not available . The present study was conducted to compare the efficacy , safety , cost-effectiveness and effects on plasminogen activator inhibitor-1 ( PAI-1 ) levels of three LMWHs -- enoxaparin , nadroparin and dalteparin . METHODS The study was a prospect i ve , r and omized , comparative , open with blinded endpoints ( PROBE design ) assessment with a 30-day follow-up . The primary endpoint of efficacy was a composite of cardiovascular death , myocardial infa rct ion , recurrent angina and need for intervention . Cost-effectiveness was calculated by calculating the incremental cost-effectiveness ratio . Plasma PAI-1 levels were estimated by ELISA . RESULTS A total of 150 patients were available for intention-to-treat analysis . There was no significant difference at 30 days in the primary endpoint or in any of the individual components in the three groups . The secondary endpoint of silent ischemia was also not significantly different . Adverse events were similar in the three groups . The PAI-1 levels were not significantly different in the three groups . The total cost of treatment in the three groups was similar . CONCLUSION Any of the three LMWHs evaluated in this study were similar with respect to efficacy , safety , PAI-1 levels and cost-effectiveness OBJECTIVE —In the Indian Diabetes Prevention Programme ( IDPP ) , a 3-year r and omized , controlled trial , lifestyle modification ( LSM ) and metformin helped to prevent type 2 diabetes in subjects with impaired glucose tolerance ( IGT ) . The direct medical costs and cost-effectiveness of the interventions relative to the control group are reported here . RESEARCH DESIGN AND METHODS —Relative effectiveness and costs of interventions ( LSM , metformin , and LSM and metformin ) in the IDPP were estimated from the health care system perspective . Costs of intervention considered were only the direct medical costs . Direct nonmedical , indirect , and research costs were excluded . The cost-effectiveness of interventions was measured as the amount spent to prevent one case of diabetes within the 3-year trial period . RESULTS —The direct medical cost to identify one subject with IGT was Indian rupees ( INR ) 5,278 ( $ 117 ) . Direct medical costs of interventions over the 3-year trial period were INR 2,739 ( $ 61 ) per subject in the control group , INR 10,136 ( $ 225 ) with LSM , INR 9,881 ( $ 220 ) with metformin , and INR 12,144 ( $ 270 ) with LSM and metformin . The number of individuals needed to treat to prevent a case of diabetes was 6.4 with LSM , 6.9 with metformin , and 6.5 with LSM and metformin . Cost-effectiveness to prevent one case of diabetes with LSM was INR 47,341 ( $ 1,052 ) , with metformin INR 49,280 ( $ 1,095 ) , and with LSM and metformin INR 61,133 ( $ 1,359 ) . CONCLUSIONS —Both LSM and metformin were cost-effective interventions for preventing diabetes among high risk-individuals in India and perhaps may be useful in other developing countries as well . The long-term cost-effectiveness of the interventions needs to be assessed BACKGROUND Endovascular coil treatment is being used increasingly as an alternative to clipping for some ruptured intracranial aneurysms . The relative benefits of these 2 approaches have yet to be fully established . The aim of this study was to compare the clinical outcome , re source consumption , and cost-effectiveness of endovascular treatment vs surgical clipping in a developing country . METHODS The study population consisted of 55 patients with aneurysmal subarachnoid hemorrhage ( SAH ) identified prospect ively from January 2004 to June 2007 . Of the 55 patients with ruptured intracranial aneurysms , 31 underwent surgical clipping , whereas 24 were treated via interventional coils . Clinical outcome at 6 months , using the modified Rankin Scale , and cost of treatment related to all aspects of the inpatient stay were evaluated in both groups . RESULTS The average age of the patients in the endovascular group was 38 years , whereas in the surgical group , it was 45 years . Most patients ( 43 ) were found to be in grade s ( 1 and 2 ) . Of these patients , 18 received coils and 25 were clipped . The remaining 12 patients were of poor grade s ( 3 and 4 ) , of which 6 had coiling and 6 underwent clipping . Most the patients ( 46/55 ) had anterior circulation aneurysms , and the rest of the patients ( 9/55 ) had posterior circulation aneurysms . The clinical outcome was similar in comparison ( good in 81 % for clipping and 83 % for coiling ) . The average total cost for patients undergoing endovascular treatment of the aneurysms was $ 5080 , whereas the average total cost of surgical clipping was $ 3127 . CONCLUSION Patients with aneurysmal SAH whom we judged to require coiling had higher charges than patients who could be treated by clipping . The benefits of apparent decrease in length of stay in the endovascular group were offset by higher procedure price and cost of consumables . There was no significant difference in clinical outcome at 6 months . We have proposed a risk scoring system to give guidelines regarding the choice of treatment considering size of aneurysm and re source allocation BACKGROUND The risk of type 2 diabetes mellitus is increased in people who have low birth weights and who subsequently become obese as adults . Whether their obesity originates in childhood and , if so , at what age are unknown . Underst and ing the origin of obesity may be especially important in developing countries , where type 2 diabetes is rapidly increasing yet public health messages still focus on reducing childhood " undernutrition . " METHODS We evaluated glucose tolerance and plasma insulin concentrations in 1492 men and women 26 to 32 years of age who had been measured at birth and at intervals of three to six months throughout infancy , childhood , and adolescence in a prospect i ve , population -based study . RESULTS The prevalence of impaired glucose tolerance was 10.8 percent , and that of diabetes was 4.4 percent . Subjects with impaired glucose tolerance or diabetes typically had a low body-mass index up to the age of two years , followed by an early adiposity rebound ( the age after infancy when body mass starts to rise ) and an accelerated increase in body-mass index until adulthood . However , despite an increase in body-mass index between the ages of 2 and 12 years , none of these subjects were obese at the age of 12 years . The odds ratio for disease associated with an increase in the body-mass index of 1 SD from 2 to 12 years of age was 1.36 ( 95 percent confidence interval , 1.18 to 1.57 ; P<0.001 ) . CONCLUSIONS There is an association between thinness in infancy and the presence of impaired glucose tolerance or diabetes in young adulthood . Crossing into higher categories of body-mass index after the age of two years is also associated with these disorders |
12,136 | 19,079,865 | Curvilinear associations were found in some analyses , with lower nutrient intakes at both extremes of sugar intake ; however , factors such as dieting and under-reporting may confound the associations observed .
Mean intakes of most micronutrients were above the RDA or reference nutrient intake except among very high consumers of sugars .
The available evidence does not allow for firm conclusions on an optimal level of added sugars intake for micronutrient adequacy and the trends that exist may have little biological significance except for a few nutrients ( for example , Fe ) .
It is established that energy intake is the prime predictor of micronutrient adequacy . | Guidelines for sugars intake range from a population mean of less than 10 % energy from free sugars , to a maximum for individuals of 25 % energy from added sugars .
The aim of the present review was to examine the evidence for micronutrient dilution by sugars and evaluate its nutritional significance . | OBJECTIVE To investigate food and nutrient intakes in 3-year-old children . SUBJECTS Eight hundred and sixty-three children resident in South West Engl and ( 69 % of those invited at this age ) , a r and omly selected sub- sample of the Avon Longitudinal Study of Pregnancy and Childhood ( ALSPAC ) . METHODS Diet was assessed using a 3-day descriptive food record . Food and nutrient intakes were compared with intakes at 18 months in the same children , with intakes in the British National Diet and Nutrition Survey ( NDNS ) of pre-school children , and with dietary reference values ( DRVs ) . RESULTS Intakes of energy and most nutrients had increased between 18 and 43 months . The macronutrient content of the diet had also changed , the percentage of energy from starch rose from 21 to 23 % and from non-milk extrinsic ( NME ) sugar from 12 to 16 % , while the polyunsaturated to saturated fat ratio increased from 0.26 to 0.33 . When compared with the NDNS , intakes of energy and all nutrients were higher with the exception of NME sugar . Energy intakes were below the estimated average requirements . Mean intakes of iron and vitamin D were below the Reference Nutrient Intake . Fewer children were eating beef at 43 months than at 18 months . Total daily meat consumption was lower than in the NDNS . The proportion of children consuming any vegetables dropped between 18 and 43 months , although fruit eating remained constant . CONCLUSIONS The diets of 3-year-olds in this study were adequate in most nutrients . Our results suggest that energy requirements of pre-school children in the 1990s are less than the DRV . Nutrient and food intakes changed between 18 and 43 months . Children were eating less meat than their counterparts in the NDNS OBJECTIVE To investigate the long-term effects of changes in dietary carbohydrate/fat ratio and simple vs complex carbohydrates . DESIGN R and omized controlled multicentre trial ( CARMEN ) , in which subjects were allocated for 6 months either to a seasonal control group ( no intervention ) or to one of three experimental groups : a control diet group ( dietary intervention typical of the average national intake ) ; a low-fat high simple carbohydrate group ; or a low-fat high complex carbohydrate group . SUBJECTS Three hundred and ninety eight moderately obese adults . MEASUREMENTS The change in body weight was the primary outcome ; changes in body composition and blood lipids were secondary outcomes . RESULTS Body weight loss in the low-fat high simple carbohydrate and low-fat high complex carbohydrate groups was 0.9 kg ( P < 0.05 ) and 1.8 kg ( P < 0.001 ) , while the control diet and seasonal control groups gained weight ( 0.8 and 0.1 kg , NS ) . Fat mass changed by -1.3 kg ( P < 0.01 ) , -1.8 kg ( P < 0.001 ) and + 0.6 kg ( NS ) in the low-fat high simple carbohydrate , low-fat high complex carbohydrate and control diet groups , respectively . Changes in blood lipids did not differ significantly between the dietary treatment groups . CONCLUSION Our findings suggest that reduction of fat intake results in a modest but significant reduction in body weight and body fatness . The concomitant increase in either simple or complex carbohydrates did not indicate significant differences in weight change . No adverse effects on blood lipids were observed . These findings underline the importance of this dietary change and its potential impact on the public health implication s of obesity Objective : To investigate whether subjects consuming a fat-reduced , high-simple carbohydrate diet ( SCHO ) are at greater risk of micronutrient inadequacy than subjects consuming a fat-reduced , high-complex carbohydrate ( CCHO ) or a normal-fat diet ( control , CD ) . Design : A 6-month r and omised controlled dietary intervention trial with a parallel design . Methods : In total , 46 overweight ( BMI : 24.4–36.3 kg/m2 ) subjects ( 19 males , 27 females ) aged 21–54 y consumed one of three ad libitum diets : SCHO , CCHO , or CD . Nutrient intake was assessed by a 7-day weighed food record . Results : Self-reported energy intake did not differ between diet groups . The lowest intake of vitamin B12 was found in the SCHO group vs CCHO ( P=0.025 ) and vs. CD ( P=0.012 ) . In men , zinc intake was lower on the SCHO diet compared to the CD diet ( P=0.018 ) . The recommendations for zinc and vitamin B12 were , however , met by all the diet groups . No other diet differences were observed . Intake of several micronutrients were insufficient in all three diet groups , although in most cases comparable to average Danish intakes . Conclusion : Zinc intake in men and vitamin B12 intake in the combined gender groups were lower on a fat-reduced , simple carbohydrate-rich diet compared to a habitual , normal-fat diet , but not below recommended levels . Sponsorship : The EU-FAIR program ( PL 95 - 809 ) , the Sugar Bureau , the European Sugar Industries , the Danish Medical Research Council , and the Danish Research and Development Programme for Food Technology BACKGROUND Nutritional intake by military personnel is typically inadequate during field exercises , potentially compromising health and performance . HYPOTHESIS Drinking a supplemental carbohydrate ( CHO ) beverage will increase total caloric intake and maintain nutritional status during military training in the desert . METHODS A total of 63 volunteers were r and omly assigned to one of two groups to receive either a CHO or placebo beverage with military rations during an 11-d desert field exercise . Fluid intake was ad libitum and adequate rations were provided . Blood sample s were collected twice to assess nutritional status , and nutrient intake was determined with consumption data . Mood state was examined by question naire . RESULTS Energy intake was significantly higher in the CHO group ( 3050 kcal x d(-1 ) vs. 2631 kcal x d(-1 ) ) , with additional CHO from the beverage providing energy with some compensation by reduced fat and protein intake . Intakes of energy , folacin , calcium , magnesium , iron , and zinc in both groups were inadequate , with intakes significantly lower ( p<0.05 ) for calcium , magnesium , and zinc in the CHO beverage group . Blood parameters of nutritional status remained within normal ranges with no differences between groups , but significant decreases were seen in pre-albumin . No changes in mood were seen during the training , nor after exposure to desert conditions . CONCLUSIONS The operational ration supplemented with a CHO beverage significantly increases CHO and energy intakes compared with st and ard rations and maintains nutritional status for short exercises . Fortification with micronutrients most at risk for deficient intake from foods may be needed for longer deployments OBJECTIVE To measure mineral intakes and the contribution of different food groups to mineral intakes in adults aged 18 - 64 years in Irel and . Intakes are reported for Ca , Mg , P , Fe , Cu and Zn . The adequacy of mineral intakes in the population and the risk of occurrence of excessive intakes are also assessed . DESIGN Food consumption was estimated using a 7-day food diary for a representative sample ( n=1379 ; 662 men , 717 women ) of 18 - 64-year-old adults in the Republic of Irel and and Northern Irel and selected r and omly from the electoral register . Mineral intakes ( Ca , Mg , P , Fe , Cu and Zn ) were estimated using tables of food composition . RESULTS Mean nutrient density of intakes was higher for women than men for Ca and Fe and increased with age for all minerals , except Ca for men and Fe for women . Meat and meat products were the major contributor to mean daily intakes of Zn ( 38 % ) , P ( 23 % ) , Fe ( 18 % ) , Cu ( 15 % ) and Mg ( 13 % ) ; dairy products ( milk , yoghurt and cheese ) to Ca ( 44 % ) , P ( 22 % ) , Zn ( 14 % ) and Mg ( 11 % ) ; bread and rolls to Fe ( 21 % ) , Cu ( 18 % ) , Ca and Mg ( 17 % ) , Zn ( 13 % ) and P ( 12 % ) ; potatoes and potato products to Cu ( 16 % ) , Mg ( 14 % ) and Fe ( 10 % ) ; and breakfast cereals to Fe ( 13 % ) . In women of all ages nutritional supplements contributed 7.6 % , 4.4 % , 3.6 % and 2.2 % of mean daily intake of Fe , Zn , Cu and Ca , respectively , while in men of all ages , nutritional supplements contributed 2.7 % , 2.3 % , 1.7 % and 0.6 % , respectively , to mean daily intakes of Fe , Zn , Cu and Ca . Adequacy of minerals intakes in population groups was assessed using the average requirement ( AR ) as a cut-off value . A significant prevalence of intakes below the AR was observed for Ca , Fe , Cu and Zn but not P. A higher proportion of women than men had intakes below the AR for all minerals . Almost 50 % of 18 - 50-year-old females had intakes below the AR for Fe , while 23 % , 23 % and 15 % of women of all ages had intakes below the AR for Ca , Cu and Zn , respectively . For men of all ages , 11 % , 8 % and 13 % had intakes below the AR for Ca , Cu and Zn , respectively . There appears to be little risk of excessive intake of Ca , Mg , P , Cu or Zn in any age/sex category . However , 2.9 % of women of all ages had intakes above the tolerable upper intake level for Fe ( 45 mg ) due to supplement use . CONCLUSION Almost 50 % of women aged 18 - 50 years had Fe intakes below the AR and relatively high proportions of women of all ages had intakes below the AR for Ca , Cu and Zn . With the possible exception of iron intake from supplements in women , there appears to be little risk of excessive intake of minerals in the adult population . Meat and meat products , dairy products ( milk , cheese and yoghurt ) , bread and rolls , potatoes and potato products and breakfast cereals are important sources of minerals ; nutritional supplements make only a small contribution to mineral intakes in the population as a whole but may contribute significantly to intakes among supplement users OBJECTIVES : To compare the response by overweight individuals , counselled in a work environment , to energy-reduced diets in which the amount of sucrose-containing foods is varied . DESIGN : Two energy-reduced diets were design ed as a weight-reducing programme . A low-sugar diet ( LSD ) providing 5 % of its energy from sucrose and a sugar-containing diet ( SCD ) providing 10 % of its energy from sucrose incorporated as sweet foods were devised . Both diets were constructed to contain about 33 % of the energy from fat . The diets , design ed to provide a deficit of 2.51 MJ/day ( 600 kcal/day ) per individual , were r and omly allocated to subjects in an 8 week parallel design study .SUBJECTS : Ninety-five subjects were recruited from a large service industry if they were more than 7 kg ( 1 stone ) in weight above body mass index ( BMI ) 25 kg/m2 . Sixty-eight subjects completed the programme . MEASUREMENTS : Fortnightly body weight measurements were taken using calibrated scales ; BMI at baseline and week 8 ; and nutrient intake using 2 day food record diaries at baseline and weeks 2 , 4 and 8 . RESULTS : Weight loss over the 8 weeks was 2.2 kg ( LSD ) and 3.0 kg ( SCD ) . BMI changed from 29.2 on the LSD and 30.1 kg/m2 SCD at baseline to 28.2 and 28.8 kg/m2 at week 8 respectively . The actual prescribed commercially added sucrose intakes were 5 % energy ( LSD ) or 10 % energy ( SCD ) . Reported percentage energy from fat was significantly lower on the SCD ( and would seem to support the theory of an inverse relationship between fat and sugar ) than on the LSD , where there was seen to be no significant reduction . There was no evidence of micronutrient dilution that could be directly attributed to the sucrose content of the diets . CONCLUSION : These results provide no justification for the exclusion of added sucrose in weight-reducing diets |
12,137 | 28,249,848 | In multivariable analysis , fewer authors were associated with selection bias ( allocation concealment ) , performance bias and attrition bias , and earlier year of publication and funding source not reported or disclosed were associated with selection bias ( sequence generation ) .
Studies published in non-English language were associated with reporting bias .
Studies evaluating CHM often fail to meet expected method ological criteria , and high- quality evidence is lacking | OBJECTIVES We appraised the method ological and reporting quality of r and omised controlled clinical trials ( RCTs ) evaluating the efficacy and safety of Chinese herbal medicine ( CHM ) in patients with rheumatoid arthritis ( RA ) . | Objective To investigate the effects of Qingre Huoxue Decoction 清热活血方 , clearing heat and promoting blood flow ; QRHXD ) , on the radiographic progression in patients with rheumatoid arthritis ( RA ) by X-ray imaging . Methods Eighty-six patients with active RA diagnosed as damp-heat and blood stasis syndrome were r and omized into a QRHXD group and a QRHXD plus methotrexate ( MTX ) group , with 43 cases in each group . After one-year of treatment , 21 cases in each group ( 42 in total ) were evaluated . Radiographs of h and s were obtained at the baseline and after 12 months of treatment . Images were evaluated by investigators blinded to chronology and clinical data , and assessed according to the Sharp/Van der Heijde methods . Results High intrareader agreements were reached ( mean intraobserver intraclass coefficients : 0.95 ) . No significant change in any imaging parameters of joint destruction was observed at 12 months in either group ; and the differences between the two groups were not significant ( P>0.05 ) . The mean of the changing score in the QRHXD group was 3.5±4.1 , and 2.4±3.5 in the QRHXD+MTX group , while the baseline radiographic score of patients in the QRHXD group was relatively higher ( 18.9±19.1 vs. 14.0±14.0 ) . The mean rates of the changing scores of the two groups were similar ( 0.24±0.28 vs. 0.25±0.44 , P=0.40 ) . The severity of progression in the two groups was also similar ( P=0.46 ) , 7 cases without radiographic progression in the QRHXD group and 8 in the QRHXD+MTX group , 3 cases with obvious radiographic progression in the QRHXD group and 1 in the QRHXD+MTX group . Conclusion Radiographic progression of RA patients in both groups is similar , indicating that the QRHXD Decoction has a potential role in preventing bone destruction BACKGROUND SKI306X , which consists of biologically active ingredients from Clematis m and sburica , Tricbosantbes kirilowii , and Prunella vulgaris , was developed and tested in pre clinical trials in Korea . Those studies found that SKI306X was associated with an anti-inflammatory and analgesic effect , and that it can delay the destruction of cartilage in rheumatoid arthritis ( RA ) . OBJECTIVE The aim of this study was to compare the pain relief and tolerability of SKI306X and celecoxib in patients with RA . METHODS This study was a 6-week , multicenter , r and omized , double-blind , double-dummy , Phase III , noninferiority clinical trial . Eligible patients were aged 18 to 80 years , had a history of RA with a disease duration of > or =3 months , and were functional American College of Rheumatology ( ACR ) class I , II , or III before entry . After a washout period of 2 weeks , patients were r and omized to SKI306X 200 mg TID or celecoxib 200 mg BID for 6 weeks . The primary end point was a change in patient assessment of pain intensity using a visual analog scale ( VAS ) . The secondary end points were a 20 % improvement in response rate as defined by the ACR ( ACR20 ) and the frequency of rescue medication use . Results after 3 and 6 weeks of treatment were compared with baseline and between treatment groups , and all patients were assessed for adverse events ( AEs ) , clinical laboratory data , and vital signs . AEs were identified based on spontaneous reports by patients during interviews conducted by the investigators and the study coordinator . RESULTS Two hundred twenty-two Korean patients from 7 medical centers were assessed and 183 were enrolled and r and omized to 1 of 2 treatment groups . Ninety-one patients ( 10 male , 81 female ; mean [ SD ] age , 52.13 [ 12.64 ] years ; mean [ SD ] duration of RA , 9.08 [ 10.23 ] years ; no. [ % ] of ACR class I , II , and III , 13 [ 14.29 ] , 44 [ 48.35 ] and 34 [ 37.36 ] patients , respectively ) received SKI306X 200 mg TID and 92 patients ( 10 male , 82 female ; mean [ SD ] age , 51.78 [ 10.94 ] years ; mean [ SD ] duration of RA , 8.78 [ 7.78 ] years ; no. [ % ] of ACR class I , II , and III , 14 [ 15.22 ] , 44 [ 47.83 ] , and 34 [ 36.96 ] patients , respectively ) received celecoxib 200 mg BID . An analysis of the change in reported pain intensity as determined by VAS ( mm ) score between baseline and week 3 ( mean [ SD ] , 13.64 [ 16.62 ] vs 14.45 [ 15.89 ] ) , and between baseline and week 6 ( 18.4 [ 20.8 ] vs 17.9 [ 19.1 ] , respectively ) suggested that SKI306X was not inferior to celecoxib . The number of patients who achieved ACR20 response rate was not significantly different between the SKI306X group and the celecoxib group at week 3 ( 16/87 [ 18.4 % ] vs 24/87 [ 27.6 % ] , respectively ) and at week 6 ( 29/87 [ 33.3 % ] vs 29/87 [ 33.3 % ] ) . The frequency of rescue medication use was not significantly different between the SKI306X group and celecoxib group at week 3 ( 54/87 [ 62.1 % ] vs 47/87 [ 54.0 % ] , respectively ) or week 6 ( 57/87 [ 65.5 % ] vs 49/87 [ 56.3 % ] ) . Drug-related AEs were reported by 27 ( 29.7 % ) patients in the SKI306X group and 22 ( 23.9 % ) patients in the celecoxib group . The most frequent drug-related AEs were epigastric pain ( 9/91 [ 9.9 % ] ) in the SKI306X group and glutamyltranferase elevation ( 4/92 [ 4.3 % ] ) in the celecoxib group . No significant between-group differences were observed in the prevalence of drug-related clinical - or laboratory-determined AEs . CONCLUSION The results of this study suggest that SKI306X was generally well tolerated and not inferior to celecoxib in regard to pain relief in these Korean patients with RA Rheumatoid arthritis ( RA ) is the most common chronic inflammatory disease with unknown causes and unknown cures in Western medicine . This double-blinded study aim ed to investigate the efficacy and safety of a widely used traditional Chinese medicine ( Paeoniflorin ( PAE ) plus cervus and cucumis polypeptide injection ( CCPI ) using disease-modifying antirheumatic drugs ( DMARD ) as a control ( methotrexate ( MTX ) plus leflunomide ( LEF ) ) . Patients were r and omly assigned to one of the three groups : PAE + CCPI , MTX + LEF , and MTX + LEF + CCPI . The primary end point was the American College of Rheumatology 20 % improvement response criteria ( ACR20 ) . The secondary end point was that of adverse effect frequencies and the speed of onset action . Our results showed that more patients in the CCPI-containing groups responded to the ACR20 during early treatment . After six months , ACR20 showed no significant difference among the three treatments . The maximum improvement in the two DMARD groups was significantly higher than that in the PAE + CCPI group ( p < 0.01 ) . CCPI made the onset action of the DMARD therapy 4.6 times faster . PAE + CCPI had significantly lower adverse event incidences than the two DMARD groups . These results indicate that PAE + CCPI appear to be a more acceptable alternative to DMARDs when patients can not use DMARDs . CCPI appears to be a beneficial add-on to DMARDs that makes the onset of action faster , especially when patients need to relieve RA symptoms as soon as possible . Although not as effective as DMARDs , PAE appears to be a safer option to substitute DMARDs for long-term RA treatment when DMARD toxicity is an issue OBJECTIVE To observe the therapeutic effect of Yangxue Tongluo Recipe ( YTR ) combined with immunosuppressive agents in the treatment of rheumatoid arthritis ( RA ) . METHODS Totally 88 RA patients were r and omly assigned to the treatment group [ 47 cases , YTR combined Methotrexate ( MTX ) + Leflunomide ( LEF ) treatment ] and the control group ( 41 cases , MTX + LEF therapy ) . All patients received 12-week treatment . Clinical symptoms and signs , laboratory tests [ erythrocyte sedimentation rate ( ESR ) , rheumatoid factor ( RF ) , and C reactive protein ( CRP ) ] , and adverse reactions were observed before and after treatment . RESULTS The total effective rate was 91.5 % ( 43/47 cases ) in the treatment group , and the total effective rate was 75.6 % ( 31/41 cases ) in the control group . There was statistical difference between the two groups ( P < 0.05 ) . The morning stiffness , the rest pain , the number of tender joints , the number of swollen joints , tender joint index , swollen joint index , ESR , RF , and CRP were significantly improved in the two groups after treatment ( P < 0.01 ) . Besides , clinical symptoms and signs , ESR , RF , and CRP were more improved in the treatment group after treatment , when compared with those in the control group ( P < 0.05 ) . Gastrointestinal discomfort was the main adverse reaction in the two groups , but the occurrence was lower in the treatment group than in the control group ( P > 0.05 ) . CONCLUSIONS The clinical efficacy of YTR combined MTX + LEF in the treatment of RA was better than using Western medicine alone . It was more safe with less adverse reactions OBJECTIVE To observe the clinical efficacy and safety of Simiao Xiaobi Decoction ( SXD ) in treating active rheumatoid arthritis ( RA ) of humid pyretic toxic Bi-Zheng ( HPTB ) syndrome type . METHODS One hundred and twenty RA patients were r and omly assigned to 2 groups , 60 in the treatment group receiving SXD , and 60 in the control group receiving methotrexate , all were treated for 12 weeks . Clinical efficacy in patients was evaluated , referring to the criteria recommended by European League Against Rheumatoism ( EULAR ) , in terms of effective rate , main symptoms , signs , scoring on symptom/sign by Chinese medicine scale and DAS28 , physical and chemical indices , long-term outcome of patients and the average therapeutic effect initiating time . Meantime , the adverse reaction was recorded . RESULTS The study was completed in 103 patients , 52 in the treated group and 51 in the control group . According to a per- protocol analysis , the effective rate was better in the treatment group than in the control group with marked difference in terms of Chinese and Western medicine respectively ( 92.3 % vs 70.6 % and 86.5 % vs 62.7 % , P<0.05 ) . Superiorities in the treatment group were also seen in the improvements of main symptoms and signs , symptom/sign scores , DAS28 scores , and long-term outcome . Moreover , the average therapeutic effect initiating time was shorter ( 5.31 + /- 0.36 weeks vs 8.28 + /- 0.45 weeks ) , while the incidence of adverse reaction was less in the treatment group than in the control group ( 6.7 % vs 43.3 % , P<0.05 ) . CONCLUSION SXD can improve the joint symptoms and general condition of RA patients of HPTB type with shorter initiating time and less adverse reaction OBJECTIVE To examine the efficacy of popular Chinese herbs used in a traditional Chinese medicine ( TCM ) combination of Ganoderma lucidum and San Miao San ( SMS ) , with purported diverse health benefits including antioxidant properties in rheumatoid arthritis ( RA ) . METHODS We r and omly assigned 32 patients with active RA , despite disease-modifying antirheumatic drugs , to TCM and 33 to placebo in addition to their current medications for 24 weeks . The TCM group received G lucidum ( 4 gm ) and SMS ( 2.4 gm ) daily . The primary outcome was the number of patients achieving American College of Rheumatology ( ACR ) 20 % response and secondary outcomes included changes in the ACR components , plasma levels , and ex vivo-induced cytokines and chemokines and oxidative stress markers . RESULTS Eighty-nine percent completed the 24-week study . Fifteen percent in the TCM group compared with 9.1 % in the placebo group achieved ACR20 ( P > 0.05 ) . Pain score and patient 's global score improved significantly only in the TCM group . The percentage , absolute counts , and CD4+/CD8+/natural killer/B lymphocytes ratio were unchanged between groups . CD3 , CD4 , and CD8 lymphocyte counts and markers of inflammation including plasma interleukin-18 ( IL-18 ) , interferon-gamma (IFNgamma)-inducible protein 10 , monocyte chemoattractant protein 1 , monokine induced by IFNgamma , and RANTES were unchanged . However , in an ex vivo experiment , the percentage change of IL-18 was significantly lower in the TCM group . Thirteen patients reported 22 episodes ( 14 in placebo group and 8 in TCM group ) of mild adverse effects . CONCLUSION G lucidum and San Miao San may have analgesic effects for patients with active RA , and were generally safe and well tolerated . However , no significant antioxidant , antiinflammatory , or immunomodulating effects could be demonstrated OBJECTIVE To vali date the European League Against Rheumatism ( EULAR ) , the American College of Rheumatology ( ACR ) , and the World Health Organization (WHO)/International League Against Rheumatism ( ILAR ) response criteria for rheumatoid arthritis ( RA ) . METHODS EULAR response criteria were developed combining change from baseline and level of disease activity attained during follow up . In a trial comparing hydroxychloroquine and sulfasalazine , we studied construct ( radiographic progression ) , criterion ( functional capacity ) , and discriminant validity . RESULTS EULAR response criteria had good construct , criterion , and discriminant validity , ACR and WHO/ILAR criteria showed only good criterion validity . CONCLUSION EULAR response criteria showed better construct and discriminant validity than did the ACR and the WHO/ILAR response criteria for RA Ninety-six patients with rheumatoid arthritis(RA ) on active phase were divided into BZX-treated group(BZXG ) and methotrexate-treated group(MTXG ) . The results showed that after 1-month treatment , symptoms and signs , such as joint tenderness , arthralgia , arthroncus , of patients in BZXG improved notably(P < 0.01 or P < 0.05 ) , while those of patients in MTXG did not improve , there was significant difference between these two groups(P < 0.01 or P < 0.05 ) . After 3-month treatment , these symptoms and signs improved in both groups(P < 0.01 or P < 0.05 ) , but BZX had a better effect than MTX . ESR , CRP , RF , C3 , IgG , IgA and IgM decreased significantly in both groups after treatment(P < 0.01 or P < 0.05 ) , ESR , CRP in BZXG decreased more and faster than those in MTXG . In BZXG the obviously efficient rat was 70 % , the total efficacy rate was 94 % , while in MTXG was 52 % and 87 % respectively . It is indicated that BZX can improve symptoms and signs of patients with RA , has better and faster effects on acute phase reaction than MTX ; and it has anti-immunologic effects similar to MTX , and has no obvious side effect The predictive roles of symptom combination traditionally evaluated in traditional Chinese medicine ( TCM ) in the treatment of rheumatoid arthritis ( RA ) were explored . Three hundred and ninety six patients were r and omly divided into 197 subjects receiving Western medicine therapy ( WM ) and 199 subjects receiving TCM therapy ( TCM ) . A complete physical examination and 18 clinical manifestations typically assessed in TCM were recorded before the r and omization . The ACR responses were used for efficacy evaluation . ACR20 and 50 responses with WM treatment were higher than in the TCM group . The 18 symptoms in RA could be clustered into 4 symptom combinations with factor analysis , which represent joint symptoms , cold pattern , deficiency pattern and hot pattern in TCM respectively . TCM would be more effective in patients with weak-symptom combination 3 ( deficiency pattern in TCM ) , and WM would be more effective in patients with symptom combination 2 ( cold pattern in TCM ) . Symptom combinations judged with TCM may have influence on the efficacy of therapy in the treatment of RA Introduction Use of complementary and alternative medicine ( CAM ) for chronic conditions has increased in recent years . There is little information , however , on CAM use among adults with clinic-confirmed diagnoses , including arthritis , who are treated by primary care physicians . Methods To assess the frequency and types of CAM therapy used by Hispanic and non-Hispanic white women and men with osteoarthritis , rheumatoid arthritis , or fibromyalgia , we used stratified r and om selection to identify 612 participants aged 18–84 years and seen in university-based primary care clinics . Respondents completed an interviewer-administered survey in English or Spanish . Results Nearly half ( 44.6 % ) of the study population was of Hispanic ethnicity , 71.4 % were women , and 65.0 % had annual incomes of less than $ 25,000 . Most ( 90.2 % ) had ever used CAM for arthritis , and 69.2 % were using CAM at the time of the interview . Current use was highest for oral supplements ( mainly glucosamine and chondroitin ) ( 34.1 % ) , mind-body therapies ( 29.0 % ) , and herbal topical ointments ( 25.1 % ) . Fewer participants made current use of vitamins and minerals ( 16.6 % ) , herbs taken orally ( 13.6 % ) , a CAM therapist ( 12.7 % ) , CAM movement therapies ( 10.6 % ) , special diets ( 10.1 % ) , or copper jewelry or magnets ( 9.2 % ) . Those with fibromyalgia currently used an average of 3.9 CAM therapies versus 2.4 for those with rheumatoid arthritis and 2.1 for those with osteoarthritis . Current CAM use was significantly associated with being female , being under 55 years of age , and having some college education . Conclusion Hispanic and non-Hispanic white arthritis patients used CAM to supplement conventional treatments . Health care providers should be aware of the high use of CAM and incorporate questions about its use into routine assessment s and treatment planning OBJECTIVE To observe the influence of Xinfengcapsule ( XFC ) on abarticular pathologic changes ( APCs ) and other indices of patients with rheumatoid arthritis ( RA ) and explore the mechanism of action of XFC in improving such changes . METHODS Three-hundred RA patients were divided r and omly into a treatment group ( n = 150 ) and control group ( n = 150 ) . A normal control ( NC ) group ( n = 90 ) was also created . Changes in cardiac function , pulmonary function , anemia indices and platelet parameters of RA patients were measured . Curative effects of the two groups were compared , and comparison carried out with the NC group . RESULTS In 300 RA patients , late diastolic peak flow velocity ( A peak ) was much higher ( P < 0.01 ) and early diastolic peak flow velocity ( E peak ) , E/A , and left ventricular fraction shortening much lower(P < 0.01 ) than those in the NC group . Vital capacity ( VC ) , forced vital capacity in one second , forced vitalcapacity ( FVC ) , maximal voluntary ventilation ( MVV ) , maximal expiratory flow in 50 % of VC ( FEF50 ) and FEF75 were lowered remarkably ( P < 0.05 or P < 0.01 ) . Platelet count ( PLT ) , plateletcrit ( PCT ) and mean platelet volume ( MPV ) increased markedly ( P < 0.05 or P < 0.01 ) , and hemoglobin ( Hb ) level decreased significantly ( P < 0.05 ) . After XFC treatment , the A peak and PLT and PCT were much lower ( P < 0.05 ) , and E/A and the number of red blood cells as well as Hb level were much higher ( P < 0.05 ) , as were FVC , MVV and FEF50 ( P < 0.05 or P < 0.01 ) , in the treatment group than those in the NC group . Total score of pain and swelling in joints , uric-acid level and high-sensitivity C-reactive protein level were much lower , and superoxide dismutase level as well as the number of CD4 + CD25 + regulation T cells ( Treg ) and CD4 + CD25 + CD127- Treg were much higher ( P < 0.05 or P < 0.01 ) in the treatment group than those in the NC group . CONCLUSION RA patients with pathologic changes in joints also suffer from lower cardiac and pulmonary functions and from parameters of anemia and platelet factors . XFC can improve the symptoms of RA patients , ameliorate their cardiac and pulmonary functions and reduce the parameters of anemia and platelet factors . XFC lowers the immune inflammatory reaction to improve APCs in RA patients Context In Chinese medicine , extracts of Tripterygium wilfordii Hook F ( TwHF , known as lei gong teng or thunder god vine ) are used to treat autoimmune and inflammatory conditions . Small clinical trials suggest that TwHF may benefit patients with rheumatoid arthritis . Contribution This trial compared TwHF extract with sulfasalazine in 121 patients with active rheumatoid arthritis who could continue oral prednisone and nonsteroidal anti-inflammatory drugs but not disease-modifying antirheumatic drugs . Among patients who continued treatment for 24 weeks , achievement of 20 % improvement in American College of Rheumatology criteria was greater with TwHF than with sulfasalazine . Adverse event rates were similar . Caution Only 62 % and 41 % of patients continued TwHF and sulfasalazine treatment , respectively , and provided 24 weeks of data . The Editors Rheumatoid arthritis is characterized by chronic inflammation of the joint lining ( synovial membrane ) ( 1 ) , which causes pain and swelling of diarthrodial joints . Over time , uncontrolled disease results in progressive joint damage , disability , and increased mortality ( 2 ) . The evolving underst and ing of the immune mechanisms that perpetuate the inflammatory response has led to effective targeted therapies , including inhibitors of inflammatory cytokines ( tumor necrosis factor , interleukin-1 , and interleukin-6 ) , modulators of activation of CD4 + T cells and dendritic cells , and agents that deplete B cells ( 3 , 4 ) . Despite the clinical efficacy of these therapies , many patients have no clinical ly meaningful response or discontinue treatment because of adverse events . Furthermore , the limited availability of effective biologics in developing countries , the need for parenteral administration of the biologics , and the relatively high cost all restrict access to these therapies in many patients with rheumatoid arthritis around the world ( 5 ) . In traditional Chinese medicine , extracts of the roots of the medicinal vine Tripterygium wilfordii Hook F ( TwHF ) ( known in China as lei gong teng or thunder god vine ) have shown therapeutic promise in treating autoimmune and inflammatory conditions as well as cancer ( 68 ) . More recently , different extracts of TwHF have been used in Chinese allopathic medicine for the treatment of autoimmune and inflammatory diseases , and small controlled trials reported good responses with TwHF extracts in patients with cadaveric kidney transplants ( 9 , 10 ) and Crohn disease ( 11 ) . Of the approximately 380 metabolites isolated from the plant , 95 % are terpenoids ( 12 , 13 ) . Three diterpenoidstriptolide , tripdiolide , and triptonide (13)are the most abundant and account for the immunosuppressive and anti-inflammatory effects observed with the root extracts in both in vitro and in vivo studies ( 6 ) . In 2 previous single-center trials of patients with rheumatoid arthritis , the extract was st and ardized by the content of triptolide and tripdiolide ( 14 ) . This made it possible to use optimal doses identified in an open-label trial ( 15 ) for the design of a subsequent small placebo-controlled study ( 16 ) . Although the number of patients was small , the apparent clinical impact and experimental results indicating potent inhibition of the expression of proinflammatory genes both in vitro and in vivo in animal models ( 1721 ) provided the rationale for our multicenter , double-blind , active comparator trial of a st and ardized TwHF extract in patients with active rheumatoid arthritis . Methods Design Overview This r and omized , controlled , 24-week study was conducted between March 2004 and October 2005 . All participants provided written informed consent to enter the trial , and the institutional review boards at the participating sites approved the protocol . All investigators and outcome assessors were blinded to group assignment of the patients . Our objective was to determine whether therapy with TwHF extract , 180 mg/d , was statistically significantly better than therapy with sulfasalazine , 2 g/d , over 24 weeks in patients with rheumatoid arthritis by using st and ard outcome measures . Setting and Participants Our study was conducted at 11 U.S. centers : 2 academic centers ( National Institutes of Health , Bethesda , Maryl and , and University of Texas , Dallas , Texas ) and 9 rheumatology subspecialty clinics ( 1 each in Dallas and Austin , Texas ; Tampa and Fort Lauderdale , Florida ; Arlington , Virginia ; Duncanville , Pennsylvania ; Wheaton and Greenbelt , Maryl and ; and Lansing , Michigan ) . Eligible patients had to be at least 18 years of age and have established rheumatoid arthritis , defined by the American College of Rheumatology ( ACR ) classification criteria ( 22 ) as rheumatoid arthritis lasting longer than 6 months . Eligible patients had active disease , defined as 6 or more painful and swollen joints , a visual analogue scale score for pain of at least 3 ( on a scale of 1 to 10 , with 1 being mild ) , and a C-reactive protein ( CRP ) level of 57.14 nmol/L or greater ( 0.6 mg/dL ) or an erythrocyte sedimentation rate ( ESR ) greater than 25 mm/h . Patients who were taking any disease-modifying antirheumatic drug at screening underwent a 28-day washout period . The use of oral prednisone , at stable doses up to 7.5 mg/d , and nonsteroidal anti-inflammatory drugs were allowed as long as the dose was not changed for 28 days before r and omization and the patient agreed to continue to take the medication during the study . Table 1 lists baseline patient characteristics . Table 1 . Patient Characteristics at Baseline R and omization and Interventions We used a computer-generated , pseudo-r and om code ( with r and om , permuted blocks ) to assign patients to treatment groups across all centers . We assigned eligible patients at a 1:1 ratio to receive either TwHF extract , 180 mg/d , or sulfasalazine , 2 g/d . In the event of gastrointestinal intolerance , the protocol allowed for temporary dose reduction of 50 % . As described elsewhere ( 15 , 16 ) , the triptolide and tripdiolide content of the ethanol and ethylacetate extract ( measured by high-performance liquid chromatography [ 22 ] ) was used to st and ardize the drug preparation for this study . On the basis of data on in vitro activity and in vivo toxicity , 30 mg of TwHF extract were formulated per capsule . Our study was conducted under the U.S Food and Drug Administrationapproved Investigational New Drug application 39191 . Outcomes and Measurements Patients were evaluated clinical ly and by laboratory measures at baseline , 2 weeks , and every 4 weeks for a total of 24 weeks . A rheumatologist or trained staff member masked to treatment allocation assessed the patients . Serum or plasma specimens were obtained from the patients at baseline , 4 weeks , and 24 weeks and stored at 80C until analysis . Radiographs of h and s and feet were obtained at baseline and 24 weeks or at study discontinuation . The primary end point was a 20 % improvement at 24 weeks , as defined by ACR criteria ( ACR 20 ) ( 23 ) . To meet criteria , a patient must have 20 % or greater improvement in both tender and swollen joints ( 68 tender and 66 swollen joints were assessed ) and 20 % or greater improvement in 3 or more of the following : the physician 's or patient 's assessment of global health status , the patient 's assessment of pain on a visual analogue scale , the patient 's assessment of function ( using a modified version of the Health Assessment Question naire [ HAQ ] ) , and the serum CRP level . Secondary end points included the efficacy of TwHF in achieving ACR 50 and ACR 70 responses at 24 weeks , the improvement in the European League Against Rheumatism Disease Activity Score 28 ( DAS 28 ) measure , and a change in the Sharpvan der Heijde score of the h and and foot radiographs ( 24 ) . Radiographs were obtained at baseline and at the end of the study and were scored by 2 independent readers who were blinded to the r and omization schedule and the radiograph sequence . Drug adherence was assessed by using a daily diary and by pill counts . Body weight , blood pressure , and serum glucose level were measured at each visit . Laboratory assessment s included ESR ( Westergren method ) ; high-sensitivity CRP with normal levels up to 38.1 nmol/L ( 0.4 mg/dL ) , which was analyzed in a central laboratory ; and interleukin-6 levels , which were measured at baseline , 4 weeks , and 24 weeks by using high-sensitivity enzyme-linked immunosorbent assay ( R&D Systems , Minneapolis , Minnesota ) . Rheumatoid factor was measured by immunonephelometry with a BNII analyzer ( Siemens Medical Solutions Diagnostics , Newark , Delaware ) , cortisol and adrenocorticotropic hormone levels by immunochemiluminescence methods with an Immulite 2500 ( Siemens Medical Solutions Diagnostics , Los Angeles , California ) , and plasma lipids by Synchron LX-20 automated analyzers ( Beckman Coulter , Brea , California ) . Safety assessment s consisted of all patients marking adverse events in their drug diaries , which were review ed on each visit . Vital signs and safety laboratory measures , including a complete blood count and a chemistry profile ( electrolyte and liver and kidney function tests ) , were recorded at each visit . Adverse events were grade d by severity according to the National Cancer Institute Common Toxicity Criteria guidelines . An electrocardiogram ( ECG ) was obtained from all patients at baseline , 2 weeks , and the end of study . After 24 weeks , no follow-up was conducted . Statistical Analysis We design ed our study to detect differences in the primary end point with greater than 90 % power at a 2-sided level of significance of 0.05 . To properly account for missing end point data due to dropouts , we used mixed-effects analyses to predict each patient 's ACR response at the end of study visit and to properly account for uncertainty in that prediction . The response was categorized according to the ACR 20 , ACR 50 , and ACR 70 criteria . In a similar manner , we compared changes in DAS 28 from baseline visit between treatment groups . We modeled the treatment group , visit number ( 2 r and om-effect terms for visit number and visit Objectives To evaluate the risk of bias tool , introduced by the Cochrane Collaboration for assessing the internal validity of r and omised trials , for inter-rater agreement , concurrent validity compared with the Jadad scale and Schulz approach to allocation concealment , and the relation between risk of bias and effect estimates . Design Cross sectional study . Study sample 163 trials in children . Main outcome measures Inter-rater agreement between review ers assessing trials using the risk of bias tool ( weighted κ ) , time to apply the risk of bias tool compared with other approaches to quality assessment ( paired t test ) , degree of correlation for overall risk compared with overall quality scores ( Kendall ’s τ statistic ) , and magnitude of effect estimates for studies classified as being at high , unclear , or low risk of bias ( metaregression ) . Results Inter-rater agreement on individual domains of the risk of bias tool ranged from slight ( κ=0.13 ) to substantial ( κ=0.74 ) . The mean time to complete the risk of bias tool was significantly longer than for the Jadad scale and Schulz approach , individually or combined ( 8.8 minutes ( SD 2.2 ) per study v 2.0 ( SD 0.8 ) , P<0.001 ) . There was low correlation between risk of bias overall compared with the Jadad scores ( P=0.395 ) and Schulz approach ( P=0.064 ) . Effect sizes differed between studies assessed as being at high or unclear risk of bias ( 0.52 ) compared with those at low risk ( 0.23 ) . Conclusions Inter-rater agreement varied across domains of the risk of bias tool . Generally , agreement was poorer for those items that required more judgment . There was low correlation between assessment s of overall risk of bias and two common approaches to quality assessment : the Jadad scale and Schulz approach to allocation concealment . Overall risk of bias as assessed by the risk of bias tool differentiated effect estimates , with more conservative estimates for studies at low risk OBJECTIVE To evaluate the clinical efficacy and safety of bushen quhan zhiwang decoction ( BQZD ) combined methotrexate ( MTX ) in treating rheumatoid arthritis ( RA ) . METHODS A prospect i ve , r and omized controlled study was carried out . RA patients of Shen deficiency and cold invading syndrome in the treatment group ( 120 cases ) were treated with BQZD and MTX ( 10 mg/week ) , while those in the control group ( 120 cases ) were treated with MTX ( 10 mg/week ) alone . The therapeutic course for all was 24 weeks . The efficacy and safety indices were evaluated at the baseline and 24 weeks after treatment , including clinical signs and symptoms , condition assessment , Health Assessment Question naire ( HAQ ) , disease activity index 28 ( DAS28 ) , laboratory parameters of erythrocyte sedimentation rate ( ESR ) and C-reactive protein ( CRP ) , safety indicators , and Chinese medical syndrome integrals . RESULTS The total effective rate was 80 . 0 % in the treatment group , better than that of the control group ( 66.7 % ) , showing statistical difference ( P < 0.01 ) . In the two groups significant improvement of clinical signs and symptoms , ESR , CRP , visual analogue scale ( VAS ) by both physicians and patients , HAQ , DAS28 , and Chinese medical syndrome integrals after treatment were shown ( P < 0.01 ) . Better effects were obtained in the treatment group in lessening tender joint numbers and swollen joint numbers , VAS by both physicians and patients , DAS28 , and Chinese medical syndrome integrals ( P < 0.05 ) . Besides , adverse reactions occurred less in the treatment group than in the control group ( P < 0.05 ) . CONCLUSIONS BQZD had roles in relieving symptoms , improving joint functions , signs , ESR , and CRP . It was an effective herb for RA patients of Shen deficiency and cold invading syndrome . It could enhance the efficacy and reduce adverse reactions of MTX through synergistic effects with MTX OBJECTIVE To observe the clinical effect of Wenhua Juanbi Recipe ( WJR ) in treating rheumatoid arthritis ( RA ) , its effects in reducing the dosage of Western medicine used and stabilizing condition of disease , as well as its influences on peripheral blood levels of tumor necrosis factor alpha ( TNF-alpha ) , interleukin 1beta ( IL-1beta ) and anti-cyclic citrullinated peptide antibody ( anti-CCP ) , for the sake of exploring its preliminary acting mechanism . METHODS One hundred patients with RA were r and omly assigned to 2 groups , the control group and the treated group , 50 in each group . All were treated with oral administration of methotrexate ( MTX,7.5 mg per week ) , sulfasalazine ( 0.5 g , tid ) and meloxicam ( Mobic , 7.5 mg , bid ) , but to the treated group WJR was given additionally . The therapeutic course for both groups was 3 months . Clinical effect , changes of symptoms and physical signs , dosages of western medicines used , and laboratory indices in 2 groups after treatment were observed , and cases of relapse 3 months after treatment were figured out . RESULTS The total effective rate in the treated group was higher than that in the control group ( 88.0 % vs 76.0 % , P<0.05 ) . The improvements in scores of symptoms and signs [ joint pain ( 0.61 + /- 0.59 ) , swelling ( 1.49 + /- 1.20 ) , tenderness ( 0.90 + /- 0.69 ) , movement ( 0.68 + /- 0.62 ) , griping strength ( 68.56 + /- 6.50 ) mm Hg , morning stiff time ( 23.26 + /- 9.26 ) min ] , and in levels of laboratory indices ( TNF-alpha , IL-1beta , anti-CCP , RF , ESR , CRP , PLT and Ig ) in the treated group after treatment were significantly superior to those in the control group ( P<0.05 or P<0.01 ) . The dosages of MTX [ ( 82.11 + /- 11.35 ) mg vs ( 94.75 + /- 10.23 ) mg ] and meloxicam [ ( 108.85 + /- 16.13 ) mg vs ( 189.63 + /- 18.44 ) mg ] used , and the relapse rate in the treated group were lower significantly ( P<0.05 , P<0.01 ) than those in the control group respectively . CONCLUSIONS Effect of combined therapy of WJR and Western medicines is superior to that of using Western medicines alone in treating RA ; WJR can reduce the dosages of Western medicines used and the relapse rate , as well as stabilize the condition of illness . It has the effects of immune regulating and anti-inflammatory reaction . Its mechanism for treating RA is possibly the inhibition on cytokines of TNF-alpha and IL-1beta OBJECTIVE The observe the clinical effect of leflunomide ( LEF ) and total glucosides of Paeony ( TGP ) on rheumatoid arthritis ( RA ) and their influences on laboratory findings . METHODS Eighty patients with RA were r and omly divided into 2 groups , 40 in each group : the treated group treated with TGP and leflunomide , and the control group treated with LEF alone , the therapeutic course for both groups was 12 weeks . Clinical effect after treatment , changes of symptoms and physical signs before and after treatment were observed and the relative laboratory indexes were detected as well . RESULTS The total effective rate in the treated group was higher than that in the control group ( 97.5 % vs 85.0 % , P < 0.05 ) . The clinical and laboratory indexes in the treated group were improved significantly after treatment ( P < 0.05 , P < 0.01 ) , with the improvement superior to those in the control group ( P < 0.05 , P < 0.01 ) respectively . There was no significant difference in adverse reaction between the two groups . CONCLUSION Combined application of TGP and LEF is superior to using of LEF alone in treating RA , owing to its quicker initiating action and less adverse reaction OBJECTIVE To investigate the efficacy and mechanism of Fengshikang ( FSK ) in treating rheumatoid arthritis ( RA ) . METHODS Thirty-eight patients with RA of damp-heat block syndrome type in Chinese medicine ( CM ) , were r and omized into two groups . They all received glucocorticoid therapy for 1 month , but FSK was administered to the 20 patients in the CM group in addition , while to the 18 in the WM group , MTX was given . Besides , a normal control group with 20 healthy subjects was set up . Blood levels of RA related indices were measured and compared . RESULTS After treatment , the levels of rheumatoid factor ( RF ) and C-reactive protein ( CRP ) were significantly reduced in both groups ( P<0.05 ) , but the reduction was more significant in the CM group ( P<0.05 ) . No significant change was found in the level of ESR after treatment and showed no significant difference between groups ( P>0.05 ) . Both hGRalpha mRNA and hGRbeta mRNA expressions were significantly higher in the patients than in the normal controls ( P<0.01 ) , they were lowered after treatment in the CM group ( P<0.01 ) , but significant reduction could only be found in level of hGRbeta mRNA in the control group ( P<0.01 ) . CONCLUSION FSK combined with glucocorticoid can effectively control the inflammatory reaction , decrease the level of hGRalpha and hGRbeta expressions and enhance the clinical efficacy in treating RA OBJECTIVE To observe the clinical efficacy and safety of Corydalis composite ( CDC ) combined with methotrexate ( MTX ) in treating rheumatoid arthritis ( RA ) . METHODS Seventy-six RA patients were r and omly assigned to 2 groups , 37 in the treated group received the combined therapy , and the 39 received MTX treatment alone , all were treated for 12 weeks . Efficacy of treatment was evaluated adopting the st and ard of American College of Rheumatology ( ACR ) , taking ACR20 as the chief criterion ; ACR50 , ACR70 as well as the clinical indexes and items in Health Account Question naire ( HAQ ) as the auxiliary criteria , including joint swelling index , joint tenderness index , holding power , morning stiffness time , resting pain , erythrocyte sedimentation rate ( ESR ) , C-reactive protein . And the adverse reaction was recorded at the same time . RESULTS After being treated for 4 , 8 and 12 weeks , the ACR20 response rate reached 35.14 % , 59.46 % and 70.27 % respectively in patients of the treated group , while that in the control group was 17.95 % , 35.90 % and 46.15 % respectively , significant difference between groups was shown in the outcome of week 8 and 12 ( P < 0.05 ) . ACR50 and ACR70 improving rate at all the time points of observation were increased in the treated group , with the ACR50 improving rate at week 12 higher than that in the control group ( 43.24 % vs. 20.51 % , P < 0.05 ) . As compared with the control group , the improvements in all the auxiliary criteria were more significant in the treated group ( P < 0.05 ) . The incidence of adverse reaction was less in the treated group than in the control group ( 32.43 % vs. 56.41 % , P < 0.05 ) , particularly in term of the damage on liver ( 0 vs. 10.26 % , P < 0.05 ) . CONCLUSION CDC combined with MTX is more effective than MTX alone in treating active RA with less adverse reaction OBJECTIVE To observe the clinical efficacy on analgesia and detumescence of Cheezheng Qingpeng ointment in the treatment of rheumatoid arthritis . METHODS From December 2004 to May 2006 , 78 patients were divided into the treatment group and the control group r and omly using PROC PLAN from SAS software . There were 40 patients in the treatment group , 30 patients were male and 10 patients were female , with an average age of ( 48.2+/-9.7 ) years , who were treated with Cheezheng Qingpeng ointment external treatment . Thirty-eight patients were in the control group , 30 patients were male and 8 patients were female , with an average age of ( 47.7+/-13.7 ) years , and were treated with Diclofenac diethylamine emugel . All the patients were treated for 2 weeks . The metacarpophalangeal joint with most severe pain and swelling was observed . The indexes including joint pain , tenderness , swelling , joint motion and morning stiffness were detected and the VAS scores were compared between the two groups . RESULTS All the patients completed the trial , 35 patients in the treatment group and 33 patients in the control group . At the end of 2 weeks , 1 patient in the treatment group obtained an excellent result , 27 good and 7 bad ; in the control group , 2 patients got an excellent result , 20 good and 11 bad . There were no statistically difference of therapeutic effects between the two groups . At the 1st week after treatment , the joint swelling score of the treatment group was ( 4.0+/-1.4 ) , which was lower than the ( 5.5+/-1.9 ) in the control group . CONCLUSION There is no obvious difference of therapeutic effects between Cheezheng Qingpeng ointment and diclofenac diethylamine emugel for the treatment of rheumatoid arthritis , but the relieving of swelling of Cheezheng Qingpeng ointment is better than that of Diclofenac Diethylamine Emugel OBJECTIVE To study the therapeutic effect and possible mechanism of total panax notoginseng saponins ( PNS ) for treatment of rheumatoid arthritis ( RA ) , and to observe its safety and influence on RA immune related inner environment . METHODS Eighty-four patients were r and omly assigned to two groups . All were treated with the routine therapy with diclofenac sodium , Leflunomide and prednisone , but for the 43 patients in the treatment group PNS was given additionally . The therapeutic course was 28 days for both groups . Clinical efficacy and change of indexes including platelet counts , immnuoglobulins ( IgG , IgA , IgM ) , complement (C)3 , rheumatoid factor ( RF ) , C-reactive protein ( CRP ) , ceruloplasmin ( CER ) , haptoglobin ( HPT ) , and alpha1-acid glycoprotein ( AAG ) were observed . RESULTS Significant improvement of clinical symptoms , including the joint swelling index , joint tenderness index , joint pain index , time of morning stiffness and VAS revealed in both groups after treatment , and the effect in the treatment group was better ( P<0.05 or P<0.01 ) . PLT , CER , AAG , HPT , CRP , IgG , IgA , IgM , C3 and RF were lowered in both groups ( P<0.01 ) , but the lowering in PLT , CER , AAG and CRP in the treatment group was more significant than that in the control group respectively ( P < 0.05 or P < 0.01 ) . CONCLUSION PNS can significantly improve the condition of patients , enhance the therapeutic effect in treating RA , through regulating the disordered immunity and improving the effect of anti-inflammatory and analgesia In a prospect i ve study of up to 3 years ' duration of 113 patients with early rheumatoid arthritis a disease activity score ( DAS ) was developed based on the clinical judgment of 6 rheumatologists . The patients were divided in groups with high and low disease activity according to explicit rules . By various statistical methods , including discriminant analysis and multiple regression analysis , a DAS could be defined . This DAS is a continuous measure consisting of the variables Ritchie articular index , number of swollen joints , erythrocyte sedimentation rate and general health measured on a visual analog scale Abstract This study is design ed to compare the efficacy and safety of traditional Chinese medicine ( TCM ) with western medicine ( WM ) in the management of rheumatoid arthritis ( RA ) . This is a 24-week , r and omized , multicenter , single-blind study comparing TCM with WM ( as used in China ) carried out between June 2002 and December 2004 in nine research centers in China , involving 489 patients . Patients were r and omized to receive TCM ( n = 247 ) , MTX and SSZ ( n = 242 ) . MTX was started at a dose of 5 mg to a final dose of 7.5–15 mg weekly . The maintenance dose was 2.5–7.5 mg weekly . The starting dose of SSZ was 0.25 g bid , increasing by 0.25 g a day once a week to a final dose of 0.5–1 g qid . The maintenance dose was 0.5 g tid to qid . Primary end point was the proportion of patients with response according to the American College of Rheumatology 20 % improvement criteria ( ACR20 ) at weeks 24 . At 24 weeks , ACR20 responses were 53.0 % in TCM group and 66.5 % in WM group , ( P < 0.001 ) at 24 weeks . ACR 50 responses were 31.6 % of TCM group and 42.6 % in WM group , ( P = 0.01 ) . ACR70 responses were 12.6 % in TCM group and 17.4 % in WM group , ( P = 0.14 ) . Side effects were observed more frequently in WM group . In this study , ACR20 , ACR50 responses at 24 weeks were significantly better in the WM treated group , by intention to treat ( ITT ) and per protocol analysis . The ACR 70 response showed no significant difference between the two groups . TCM , while effective in treating RA , appears to be less effective than WM in controlling symptoms , but TCM is associated with fewer side effects The study is to observe the therapeutic effects of qingluo tongbi granules ( QTG ) in patients with rheumatoid arthritis ( RA ) and the changes of immune indexes . In this series there are 63 patients with RA of the type of yin-deficiency and heat in collaterals treated with QTG as the treated group and 55 patients of the same type treated with Tripterygium glycosides as the control group . As a result , in the treated group , the curative rate is 9.52 % and markedly effective rate 38.10 % , with a total effective rate of 90.48 % , while the corresponding rates in the control group are 0 , 20.00 % and 83.64 % , respectively . The curative effect in the treated group is better than that in the control group ( P<0.05 ) . Besides , no obvious adverse reactions are found in the treated group . Therefore it is concluded that as a new medicinal preparation QTG is safe and effective in the treatment of RA BACKGROUND In China , patients with rheumatoid arthritis ( RA ) are often treated with traditional Chinese herbal medicine . There are certain advantages of traditional Chinese medicine therapy in treatment of RA . OBJECTIVE To assess the efficacy and adverse reaction of Shenshi Qianghuo Dihuang Decoction ( SQDD ) , a compound traditional Chinese herbal medicine , in treatment of RA . DESIGN , SETTING , PARTICIPANTS AND INTERVENTIONS This was a 24-week prospect i ve , r and omized , controlled trial . Ninety RA patients meeting inclusion criteria from Shanghai Municipal Hospital of Traditional Chinese Medicine were r and omly assigned to receive SQDD or methotrexate ( MTX ) with 45 cases in each group . The patients in SQDD group were orally administered with SQDD twice daily , and the patients in MTX control group were treated by oral administration of 15 mg MTX once a week . All the RA patients were treated for 24 weeks . MAIN OUTCOME MEASURES The primary outcome was the number of patients achieving the American College of Rheumatology 20 % response . Clinical and laboratory parameters including tender joint count and swollen joint count , patient 's global assessment and physician 's global assessment ( using a 0 - 10 cm visual analogue scale ) , duration of morning stiffness , plasma C-reactive protein ( CRP ) level , erythrocyte sedimentation rate ( ESR ) and value of anti-cyclic citrullinated peptide ( CCP ) antibody were assessed . RESULTS After 24-week treatment , the response rates in SQDD group and MTX group were 62.53 % ( 24/41 ) and 67.5 % ( 28/40 ) respectively , and there was no statistical difference between the two groups ( P>0.05 ) . The patient 's global assessment and physician 's global assessment , morning stiffness , grip strength , tender joint count , swollen joint count and the levels of ESR , CRP and anti-CCP antibody in SQDD and MTX groups were improved significantly as compared with those before treatment , and there were no significant differences between the two groups . The efficacy of MTX in improving rest pain and joint tenderness was better than that of SQDD ( P<0.05 ) . The incidence rate of adverse reactions in SQDD group was 9.75%(4/41 ) , significantly lower than 32.5 % ( 13/40 ) in MTX group ( P<0.05 ) . CONCLUSION SQDD has a therapeutic effect on RA , and the adverse reactions are less than MTX CONTEXT Recent reports highlight gaps between guidelines -based treatment recommendations and evidence from clinical trials that supports those recommendations . Strengthened reporting requirements for studies registered with Clinical Trials.gov enable a comprehensive evaluation of the national trials portfolio . OBJECTIVE To examine fundamental characteristics of interventional clinical trials registered in the Clinical Trials.gov data base . METHODS A data set comprising 96,346 clinical studies from Clinical Trials.gov was downloaded on September 27 , 2010 , and entered into a relational data base to analyze aggregate data . Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular , mental health , and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States . MAIN OUTCOME MEASURES Characteristics of registered clinical trials as reported data elements in the trial registry ; how those characteristics have changed over time ; differences in characteristics as a function of clinical specialty ; and factors associated with use of r and omization , blinding , and data monitoring committees ( DMCs ) . RESULTS The number of registered interventional clinical trials increased from 28,881 ( October 2004-September 2007 ) to 40,970 ( October 2007-September 2010 ) , and the number of missing data elements has generally declined . Most interventional trials registered between 2007 and 2010 were small , with 62 % enrolling 100 or fewer participants . Many clinical trials were single-center ( 66 % ; 24,788/37,520 ) and funded by organizations other than industry or the National Institutes of Health ( NIH ) ( 47 % ; 17,592/37,520 ) . Heterogeneity in the reported methods by clinical specialty ; sponsor type ; and the reported use of DMCs , r and omization , and blinding was evident . For example , reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials ( adjusted odds ratio [ OR ] , 0.11 ; 95 % CI , 0.09 - 0.14 ) , earlier-phase vs phase 3 trials ( adjusted OR , 0.83 ; 95 % CI , 0.76 - 0.91 ) , and mental health trials vs those in the other 2 specialties . In similar comparisons , r and omization and blinding were less frequently reported in earlier-phase , oncology , and device trials . CONCLUSION Clinical trials registered in Clinical Trials.gov are dominated by small trials and contain significant heterogeneity in method ological approaches , including reported use of r and omization , blinding , and DMCs OBJECTIVE To assess the therapeutic efficacy and safety of Kunxian Capsule ( KXC ) in treatment of rheumatoid arthritis ( RA ) . METHODS R and omized positive parallel controlled and multi-center open test method was adopted . 240 RA patients of mild/moderate degree were r and omly assigned to three groups equally , i.e. , KXC group ( who took KXC ) , the methotrexate ( MTX ) group ( who took MTX ) , and the KXC + MTX group ( who took KXC and MTX simultaneously ) , respectively . The therapeutic course for them all was 12 weeks . The effect of the treatment was assessed in items of DAS28 , ACR20 , and ACR50 ; number of joints with pain and swelling ; VAS score of pain , tiredness , and general condition ; time of morning stiffness ; bilateral grip strength ; HAQ score , as well as blood levels of erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , rheumatoid factor ( RF ) , anti-CCP antibody , and platelet count . RESULTS By the end of the 4th week , the improvement of ACR20 , ACR50 , DAS28 efficacy judgment , and DAS28 score in the KXC + MTX group were much better than those in the other two groups , with statistical difference ( P<0.05 ) . The total effective rate was 88 . 6 % and the markedly effective rate was 51.8 % in the KXC + MTX group at the 12 th week . The Improvement was more obviously shown in all groups after treatment ( all P<0.05 ) . Better effects in reducing VAS scores of pain and tiredness were shown in the KXC group and the KXC + MTX group . The effects of KXC + MTX were superior to the other two groups in terms of swollen joint numbers , pain joints , grip strength ( assessed by research er ) , as well as VAS score of general condition and HAQ score ( assessed by both patients and research er , P<0.05 ) . But the differences among groups in improving morning stiffness and the incidence rate of adverse events were in- significant . CONCLUSIONS KXC could relieve symptoms , improve joint functions , physical signs , and laboratory indices of RA patients with less adverse reaction . It was synergistic with MTX OBJECTIVE To investigate the therapeutic effects of Sanwushaoxie decoction on alternations of serum cytokines in patients with rheumatoid arthritis ( RA ) . METHOD Sixty-three ( 63 ) RA patients were selected and r and omly divided into 2 groups , with the treatment group administered with Sanwushaoxie decoction , one prescription , 2 times a day , while patients in the control group were given Common Threewingnut Root polyglycoside 20 mg a time , 3 times a day . The treatment was lasted for 60 days . Serum concentrations of IL-6 , TNF-alpha , IL-4 , IL-10 were observed during the treatment . RESULT The clinical effecacy and the experimental indexes were significantly improved in the treatment group than those did in the control group ( P < 0.01 , P < 0.05 ) . There were significant differences of serum levels of 4 cytokines within the treatment group before and after the treatment ( P < 0.01 , P < 0.05 ) . The serum levels of IL-4 , IL-10 were significantly increased in treatment group compared with those did in the control group ( P < 0.01 ) . CONCLUSION Sanwushaoxie decoction is an effective agent in regulating cytokines , improving symptoms and experimental indexes in patients with RA OBJECTIVE To observe the effect and adverse reaction of small doses Tripterygium wilfordii polyglycoside ( TWP ) combined with methotrexate ( MT ) in treating rheumatoid arthritis ( RA ) . METHODS Seventy RA patients were r and omly divided into two groups , the control group ( 35 patients ) and the TWP combined MT Group ( TWPM group ) . Both of them were continued to use the non-steroidal anti-inflammatory drugs . The control group took MT 15 mg orally , once every week ; the TWPM group took TWP 10 mg orally , 3 times a day , and MT 7.5 mg orally once every week . The clinical effect and adverse reaction after treatment were evaluated . RESULTS The markedly effective rate in the control group and the TWPM group was 28.6 % and 34.3 % respectively , with no significant difference ( P > 0.05 ) . Data of symptoms and signs , erythrocyte sedimentation rate ( ESR ) , rheumatoid factor ( RF ) were determined respectively with significant difference ( P < 0.01 ) . The rate of adverse reaction was 20 cases-times in the control group and 8 cases-times in the TWPM group . CONCLUSION MT combined small doses of TWP in treating RA has better effect and less adverse reactions than un-combined MT OBJECTIVE To study the clinical efficacy of Suogudan Granule ( SGDG ) in the treatment of rheumatoid arthritis ( RA ) . METHODS Ninety patients with RA were r and omly divided into the treated group and the control group . The treated group was administered orally with SGDG 6 g each time , thrice a day , while the control group with the combined therapy of Fenbid Capsules 0.3 g each time , twice a day and Tripterygium tablet 20 mg each time , thrice a day . The treatment course for both groups was 6 weeks . The changes of clinical symptoms and signs , and laboratory indices such as erythrocyte sedimentation rate ( ESR ) , rheumatoid factor ( RF ) , antistreptolysin O ( ASO ) , routine examination of blood and urine , liver and kidney function , etc . before and after treatment were observed . RESULTS ( 1 ) The total effective rate in the treated group ( 88.0 % ) was obviously higher than that in the control group ( 67.5 % ) with significant difference ( P < 0.05 ) . ( 2 ) The improvement in arthralgia , joint swelling , time of morning stiffness , 15-meter walking , analgesia initiation and persistence in the treated group was better than that in the control group ( P < 0.05 , P < 0.01 ) , but there was no obvious difference in improvement of joint tenderness , range of joint motion , grip strength , and initiating detumescence time ( P > 0.05 ) . ( 3 ) The improvement in ESR and RF in the treated group was better than that in the control group with significant difference ( P < 0.05 ) . The negative-conversion rate of ASO in the treated group was also higher than that in the control group ( P < 0.01 ) . ( 4 ) No evident abnormality in blood , urine , liver or kidney function was found in either group . CONCLUSION SGDG is effective and safe for the treatment of RA OBJECTIVE To observe the effect of strengthening Pi and activating blood circulation therapy ( SPAB ) on serum levels of adrenocorticotrophic hormone ( ACTH ) and vascular endothelial growth factor ( VEGF ) in rheumatoid arthritis ( RA ) patients . METHODS Seventy RA patients were r and omly assigned to 3 groups . The 30 in the Chinese medicine ( CM ) group were treated with SPAB ; the 20 in the Western medicine ( WM ) group were treated with indomethacin and methopterin ; and the 20 in the CM-WM group were treated with the combination of the therapy in the above two groups , and the course of treatment was 3 months for all . Serum levels of ACTH and VEGF were determined before and after treatment . RESULTS The total effective rate in the CM group was 80.0 % , WM group 85.0 % and CM-WM group 95.0 % , the last one showed the best efficacy ( P<0.05 ) . Serum level of ACTH increased and level of VEGF decreased after treatment in all groups ( P<0.05 or P<0.01 ) , but the increment/decrement in the CM-WM group was higher than that in the other two groups ( P<0.01 ) , while comparison between that in the CW group and WM group showed insignificant difference . CONCLUSION SPAB therapy has the effect in alleviating the condition of RA , similar to that of Western medicine , it can increase the serum level of ACTH and decrease the serum level of VEGF remarkably in RA patients OBJECTIVE To examine the safety and efficacy of an extract of Tripterygium wilfordii Hook F ( TWHF ) in the treatment of patients with rheumatoid arthritis ( RA ) . METHODS An ethanol/ethyl acetate extract from the roots of TWHF was prepared and used in a prospect i ve , double-blind , placebo-controlled study in patients with longst and ing RA in whom conventional therapy had failed . Patients were r and omly assigned to receive either placebo or low-dose ( 180 mg/day ) or high-dose ( 360 mg/day ) extract for 20 weeks , followed by an open-label extension period . Clinical responses were defined as 20 % improvement in disease activity according to the American College of Rheumatology criteria . Side effects were actively queried and recorded at each visit . RESULTS A total of 35 patients were enrolled in the trial ; 21 patients completed the 20-week study . One patient from each group withdrew because of side effects . Twelve , 10 , and 10 patients in the placebo , low-dose , and high-dose groups , respectively , completed at least 4 weeks of treatment . Of these patients , 8 and 4 in the high-dose and low-dose groups , but none in the placebo group , met criteria for clinical response . Four , 4 , and 7 patients in the placebo , low-dose , and high-dose groups , respectively , were enrolled in the open-label extension ; of these , 2 , 4 , and 5 patients , respectively , met criteria for clinical response . The most common side effect was diarrhea , which caused 1 patient in the high-dose group to withdraw from the trial . No patients withdrew because of adverse events during the open-label extension . CONCLUSION The ethanol/ethyl acetate extract of TWHF shows therapeutic benefit in patients with treatment-refractory RA . At therapeutic dosages , the TWHF extract was well tolerated by most patients in this study OBJECTIVE To search for a therapeutic program for increasing the therapeutic effect of western medicine on rheumatoid arthritis ( RA ) . METHODS Ninety-six cases of RA were r and omly assigned to a treatment group and a control group , 48 cases in each group . The treatment group were treated with heat electroacupuncture instrument with Chinese herb iontophoresis , combined with Meloxicam , Salazosulfamide , and Methotrexate . The control group with simple the western medicine . After treatment of a month , changes of the morning stiff duration , grasp strength , number of tenderness joints , tenderness index , joint rest pain , number of swelling joints , swelling index , assessment of the patient and doctor , and blood rheumatism factor ( RF ) , C-response protein ( CRP ) , erythrocyte sedimentation rate ( ESR ) , the white blood cell ( WBC ) and platelet counts ( PLT ) were investigated . RESULTS The effective rate was 79.2 % in the treatment group and 52.1 % in the control group , the treatment group being significantly better than the control group ( P < 0.01 ) . After treatment of one month , morning stiff duration , average grasp strength of the both h and s , tenderness of joint and swelling of joints significantly improved ( P < 0.01 ) , with the treatment group being superior to the control group ( P < 0.01 ) . After treatment , blood RF , CRP , ESR , WBC and PLT decreased in the two groups ( P < 0.01 ) , and the decreases of blood CRP , ESR , PLT in the treatment group were more significantly as compared with the control group ( P < 0.01 ) . CONCLUSION The therapeutic effect of heat needle combined with herb iontophoresis and western medicine is superior to simple medicine for treatment of rheumatoid arthritis OBJECTIVE To observe the clinical effects of Biqi Capsule ( BQC ) combined with methotrexate ( MTX ) for treatment of rheumatoid arthritis ( RA ) , and to study an effective protocol of RA treated by integrative medicine . METHODS One hundred and thirty-eight patients with RA were r and omly assigned to Group I ( 44 cases , treated by BQC ) , Group II ( 46 cases , treated by MTX ) , and Group III ( 48 cases , treated by BQC combined with MTX ) . The therapeutic course for each group was 12 weeks . The degree of joint pain , the tender joint number , the tender joint index , the swollen joint number , the swollen joint index , the two-h and grip , the morning stiffness time , and related laboratory indices were observed in each group before and after treatment . The adverse reactions were recorded . RESULTS Compared with before treatment , there was statistical difference in the degree of joint pain , the tender joint number , the tender joint index , the swollen joint number , the swollen joint index , the two-h and grip , the morning stiffness time , erythrocyte sedimentation rate ( ESR ) , C-reactive protein ( CRP ) , and rheumatoid factor ( RF ) in the 3 groups ( P < 0.05 , P < 0.01 ) . Besides , better results were obtained in Group III ( P < 0.01 ) . As for the inter-group therapeutic efficacy , better results were obtained in Group III ( P < 0.01 ) . The gastrointestinal discomfort was the only adverse reaction in the 3 groups . No treatment was given due to its milder symptoms without any effects on the treatment . CONCLUSIONS BQC showed favorable effects on treating RA with no obvious adverse reaction . BQC combined with MTX showed better clinical efficacy than use of BQC or MTX alone . It could reduce the adverse reactions of MTX . BQC combined with MTX could reduce the toxic reactions and enhance the therapeutic effects , indicating it was an effective treatment program for RA 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 OBJECTIVE To observe the curative effect of Xinfeng Capsule ( XC ) in treatment of rheumatoid arthritis ( RA ) . METHODS Recruited were 80 active RA patients , who were r and omly assigned to the normal control group and the treatment group , 40 in each group . All patients received the same routine anti-rheumatic treatment : Methotrexate 10 mg per week ; Diclofenac 50 mg when pain was obvious , twice daily . Patients in the treatment group took XC 3 tablets each time , thrice daily . All treatment lasted for 12 consecutive weeks . Serum iron ( SI ) , serum ferritin ( SF ) , transferrin ( TRF ) ; and RA disease activity index ( DAS-28 ) were detected in all patients . RESULTS XC could improve HAQ , DAS-28 , hypersensitive C reactive protein ( hs-CRP ) , prostagl and ins A ( PGA ) , erythrocyte sedimentation rate ( ESR ) , number of swelling joints , number of tender joints , and morning stiffness time in acute RA patients , showing statistical difference when compared with those of the control group ( P < 0.01 , P < 0.05 ) . Compared with the control group , SI , SF , DAS-28 , and TRF significantly decreased in the treatment group ( P < 0.05 ) . CONCLUSION XC could improve DAS-28 , and SI reserve in patients with active RA , and lower DAS-28 related indicators OBJECTIVE To observe the clinical efficacy of methotrexate ( MTX ) combined with total glucosides of Peony ( TGP ) on rheumatoid arthritis ( RA ) . METHODS Sixty-one RA patients were divided into 2 groups , 30 patients in the MTX group were only administered orally with MTX , while 31 patients in the combined treated group were treated with MTX plus TGP , the therapeutic course for both groups was 3 months . RESULTS The total effective rate was 90 % , 94 % , 100 % in the MTX plus TGP group , and 87 % , 90 % , 94 % in the MTX group at 4 , 8 and 12 weeks after treatment respectively , comparison of the therapeutic effect between the two groups showed insignificant difference ( P > 0.05 ) . The erythrocyte sedimentation rate ( ESR ) and the level of C-reactive protein were significantly decreased in both groups , but the decrement in the MTX plus TGP group was more than those in the MTX group . CONCLUSION MTX plus TGP treatment is characterized by quick initiating , with stable clinical efficacy , few side effects and high compliance , it is more suitable for aged RA patients Objectives To compare the efficacy and safety of Tripterygium wilfordii Hook F ( TwHF ) with methotrexate ( MTX ) in the treatment of active rheumatoid arthritis ( RA ) . Methods Design : a multicentre , open-label , r and omised controlled trial . All patients were assessed by trained investigators who were unaware of the therapeutic regimen . Intervention : 207 patients with active RA were r and omly allocated ( 1:1:1 ) to treatment with MTX 12.5 mg once a week , or TwHF 20 mg three times a day , or the two in combination . At week 12 , if reduction of the 28-joint count Disease Activity Score ( DAS28 ) was < 30 % in the monotherapy groups , the patient was switched to MTX+TwHF . The primary efficacy point was the proportion of patients achieving an American College of Rheumatology ( ACR ) 50 response at week 24 . Results 174/207 ( 84.1 % ) patients completed 24 weeks of the trial . In an intention-to-treat analysis , the proportion of patients reaching the ACR50 response criteria was 46.4 % ( 32/69 ) , 55.1 % ( 38/69 ) and 76.8 % ( 53/69 ) , respectively , in the MTX , TwHF and MTX+TwHF groups ( TwHF vs MTX monotherapy , p=0.014 ; MTX+TwHF vs MTX monotherapy , p<0.001 ) . Similar statistically significant patterns at week 24 were found for ACR20 , ACR70 , clinical Disease Activity Index good responses , EULAR good response , remission rate and low disease activity rate . Significant improvement in the Health Assessment Question naire and 36-item Short-Form Health Survey question naire scores from baseline to week 24 was seen in each treatment arm ( p<0.05 ) , though no significant difference was found among the treatment arms ( p>0.05 ) . The result of per- protocol analysis agreed with that seen in the intention-to-treat analysis . Seven , three and five women in the TwHF , MTX and combination groups , respectively , developed irregular menstruation ( TwHF vs MTX monotherapy , p=0.216 ) . Conclusions TwHF monotherapy was not inferior to , and MTX+TwHF was better than , MTX monotherapy in controlling disease activity in patients with active RA . Trial registration number NCT01613079 R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly OBJECTIVE To observe the effectiveness and safety of a therapy combining disease with syndrome on rheumatoid arthritis . METHODS Eighty patients with rheumatoid arthritis belonging to syndrome of damp-heat obstruction were r and omly divided into a treatment group and a control group according to stratified blocked r and omization method . Forty cases in the control group orally took Loxoprofen Sodium Tablet and Leifumite Tablet and the other 40 cases in the treatment group orally took a Chinese medicine for 12 weeks as a course of treatment . ACR therapeutic effect was used as the st and ard for evaluating the total therapeutic effect . RESULTS After 12 weeks of treatment , there was a statistical difference ( P < 0.01 ) in the improvement of VAS score , morning stiffness time , number of swelling joints , index of swelling joints , number of joints with tenderness , index of joints with tenderness , average grip strength of both h and s , DSA28 score , HAQ , patient 's assessment , physician 's assessment , ESR , CRP and RF in both groups . The improvement of morning stiffness time , number of swelling joints , index of swelling joints , grip strength , HAQ and patient 's assessment in the treatment group was much better than that in the control groups with statistical difference ( P < 0.05 ) . ACR20 , ACR50 and ACR70 was 27.5 % ( 11/40 ) , 37.5 % ( 15/40 ) and 22.5 % ( 9/40 ) respectively in the treatment group and 40 % ( 16/40 ) , 27.5 % ( 11/42 ) and 10.0 % ( 4/40 ) respectively in the control group with statistical difference ( P < 0.05 ) in the superiority of the treatment group over the control group . The incidence of adverse reaction in the control group was higher than that in the treatment group ( P < 0.05 ) . CONCLUSION Definite therapeutic effect and high safety can be achieved in using the therapy combining disease with syndrome to treat rheumatoid arthritis belonging to syndrome of damp-heat obstruction To verify the therapeutic effects of the method of softening and lubricating the joints , and calming the endogenous wind in case of rheumatoid arthritis ( RA ) with the syndrome of channel blockage due to yin deficiency , 60 RA patients with the syndrome of channel blockage due to yin deficiency were r and omly divided into a treatment group ( 40 cases ) and a control group ( 20 cases ) and treated respectively by the above method for the former and with Zheng Qing Feng Tong Ning Tablets ( [ symbol : see text ] ) for the latter . The result turned out to be that the effect in the treatment group was very satisfying . The treatment group obtained a better result in the accumulated points of syndrome and RA , morning rigidity of the joints , grip strength , 20 m walking time and erythrocyte sedimentation rate ( ESR ) ( P < 0.01 or P < 0.05 ) . The above indicates that channel blockage due to yin deficiency is an important pathogenesis of RA , and calming the endogenous wind is a method of choice for treating RA 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 ) OBJECTIVE To investigate the therapeutic effect of Lugua polypeptide on active rheumatoid arthritis ( RA ) . METHODS Fifty patients with active RA were selected for the study and were r and omly divided into study group and control group . Patients in study group were treated with Lugua polypeptide intravenously at a dose of 16 mg per day and those in control group were given Celecoxib 200 mg twice a day for successive 2 weeks . Two groups were given the same basic treatment . Tenderness and swelling of joints , morning stiffness , erythrocyte sedimentation rate , C-reactive protein , rheumatoid factor and so on were recorded before and after treatment . RESULTS The above index on joints in study group was significantly improved compared with that in control group and the level before treament . No apparent side effects were observed . CONCLUSION Lugua polypeptide is effective and safe on active RA . It is a promising agent in the treatment of RA OBJECTIVE To formulate a comprehensive treatment program for rheumatoid arthritis arthralgia by clinical observing the efficacy of Xiaoyan Zhitong Paste ( XZP ) . METHODS Adopted was stratified , block r and omized , double-blinded , placebo parallel controlled method . Subjects were assigned to the treatment group and the placebo group . Those in the treatment group were treated by external application of XZP , one to two pastes each time , covering the painful area , exchange once per 24 h , with one-day interval during a 7-day consecutive medication , two 7-days of treatment consisting of one therapeutic course . XZP placebos were applied for those in the placebo group in the same medication way . Joint pain and VAS were taken as main indices for observing the clinical efficacy of XZP . RESULTS The improvement of the analgesic effect and the Chinese medical syndrome efficacy of XZP were superior to that of the placebo . CONCLUSION XZP showed obvious effect in treating rheumatoid arthritis arthralgia with no obvious adverse reaction Combination use of methotrexate ( MTX ) and leflunomide ( LEF ) has been proved effective in the treatment of active rheumatoid arthritis ( RA ) . However , previous trials have documented that both are associated with increased incidence of liver toxicity . As active compounds extracted from the roots of the traditional Chinese herb Paeonia lactiflora Pall , total glucosides of paeony ( TGP ) have been shown to have anti-inflammatory , hepatoprotective and immuno-regulatory activities , without evident toxicity or side effects . In this 24-week , open label , r and omized multicenter clinical trial , we investigated the efficacy of TGP and the protective effect on hepatotoxicity in the combination treatment with LEF and MTX for patients with active RA . A total of 204 patients with active RA ( DAS28>3.2 ) recruited from 3 regional referral centers were enrolled and received MTX and LEF combination therapy ( MTX 10 mg/week plus LEF 20 mg/day ) with or without TGP for up to 24 weeks by r and omization . Hepatotoxicity was defined as an increase of at least 1.5-fold the upper limits of normal ( ULN ) of alanine aminotransferase ( ALT ) or aspartate aminotransferase ( AST ) . Significantly less frequent hepatotoxicity was observed in patients with TGP than those without ( 9.5 % vs 34.8 % , p < 0.001 ) at 12 weeks . The proportion of patients whose ALT or AST levels were > 1.5 to ≤2 times and > 2 to ≤3 times the ULN were lower in TGP group than the control ( 1.9 % vs 10.1 % , 2.9 % vs 12.4 % , p < 0.05 respectively ) . More patients in the TGP group achieved a European League Against Rheumatism ( EULAR ) good response or moderate response at 12 weeks , although there is no statistical significance . Similar results were observed at 24 weeks . Our preliminary study demonstrates the hepatoprotective and additive role of TGP in combination with MTX and LEF in the treatment of active RA Based on detailed explanation of the herbal CONSORT statement , and the consideration of the character of traditional Chinese drugs , to discuss the st and ardization of reporting traditional Chinese drug trials . The st and ards of reporting traditional Chinese drug trials are not consoli date d yet . In the year 2006 , Reporting R and omized , Controlled Trials of Herbal Interventions : An Elaborated CONSORT Statement was developed by the CONSORT group and published . This herbal CONSORT statement includes 5 parts , and totally 22 items , in which the items of participant criteria , intervention , control setting and outcomes , et al. are elaborated to be adaptable to herbal intervention trials . This herbal CONSORT statement has provided valuable basis for the development of st and ards of reporting traditional Chinese drug trials , though it is not completely adaptive to be the reporting st and ards in consideration of the background theory and the animal drugs and mineral drugs that traditional Chinese drugs contain . The proper reporting st and ards of traditional Chinese drug trials should take the different types of drugs and the different purpose s of trials into consideration . The trial reports of drugs that must be applied under the instruction of traditional Chinese medicine ( TCM ) theory should report participant criteria that include TCM syndrome differentiation and other important characters of TCM interventions OBJECTIVE To explore the therapeutic efficacy of external application of Compound Tripterygium wilfordii ( CTW ) for treating rheumatoid arthritis ( RA ) on the basis of treatment by integrative medicine . METHODS Totally 67 active RA patients of damp-heat stagnation syndrome were r and omly assigned to the external application group ( 35 cases ) and the placebo group ( 32 cases ) . The reaction st and ard by American College of Rheumatology and Disease Activity Score ( DAS ) were taken as the indices for therapeutic assessment . A r and omized controlled , single blind clinical trial was performed for 4 weeks , with a 3-month follow-up . The statistical analyses were performed using intention to treat analysis set ( ITT ) . RESULTS After treatment the rate of reaching ACR20 was 34.3 % and 12.5 % in the external application group and the placebo group respectively . The mean for the average drop of DAS28 ratings was 1.07 in the external application group and 0.40 in the placebo group , showing statistical difference ( P < 0.05 , P < 0.01 ) . As for the safety , there was no effect on the menstruation in the external application group . Only mild skin allergy occurred in 2 cases of the external application group , but they were alleviated after drug withdrawal . CONCLUSIONS External application of CTW could control the condition of RA and reduce the disease activity of RA . It had better safety OBJECTIVE To observe the clinical efficacy of Compound Xiatianwu tablets in the treatment of active rheumatoid arthritis . METHOD One hundred and eighty cases with active rheumatoid arthritis were r and omly divided into the control group ( 60 cases ) with leflunomide , sulfasalazine , and celecoxib ; the treatment group ( 120 cases ) given compound Xiatianwu tablets on the basis of the control group , 2 tablets each time , 3 times/day , with the course of treatment of 3 month . Patients of the two groups were observed for clinical symptoms , erythrocyte sedimentation rate , C-reactive protein , rheumatoid factor , and immunoglobulin changes before and after the treatment . RESULT The treatment group showed an overall efficiency of 94 . 2 % , the Xiatianwu group showed an overall efficiency of 80 . 0 % , while the control group showed an overall efficiency of 81.7 % . The difference among the three groups was statistically significant ( P < 0 . 05 or P < 0 . 01 ) , indicating that the treatment group was superior to the Xiatianwu group , while the Xiatianwu group was superior to the control group . CONCLUSION Compound Xiatianwu tablets has remarkable effect in the treatment of active rheumatoid arthritis OBJECTIVE To observe the short-term clinical efficacy of compound Xiatianwu combined with methotrexate ( MTX ) in treating rheumatoid arthritis . METHOD One hundred and four patients with rheumatoid arthritis were r and omly divided into two groups : 64 cases in the combined treatment group who was treated with compound Xiatianwu combined with MTX , and the remaining 40 cases in the control group which was only treated with MTX . The changes in ACR20 , ACR50 , ACR70 and laboratory indexes including anti-cyclic citrulline polypeptide , rheumatoid factor , erythrocyte sedimentation rate , high sensitivity creative protein were compared before and after treatment . Adverse reactions in the two groups were observed as well . RESULT After being treated for 3 months , the ACR20 improvement rate reached 59.4 % in the combined treatment group , higher than 35 % in the control group , with significant statistical difference ( P < 0.05 ) ; The ACR50 improvement rate reached 32 . 8 % the treated group , also higher than 17.5 % in the control group , with significant statistical difference ( P < 0.05 ) . After treatment for three months , both groups showed remarkable improvement in anti-cyclic citrulline polypeptide , rheumatoid factor , erythrocyte sedimentation rate and high sensitivity creative protein compared with that before treatment , demonstrating statistical significance ( P < 0 . 05 ) . The combined treatment group displayed more significant improvement in erythrocyte sedimentation rate and high sensitivity creative protein as well as much less adverse reactions than the MTX group . CONCLUSION Compound Xiatianwu combined with MTX can effectively improve clinical symptoms of RA patients and laboratory indexes , and shows higher medication safety OBJECTIVE To investigate the toxicity attenuation and efficacy potentiation effect of liquorice on treatment of rheumatoid arthritis ( RA ) with Tripterygium wilfordii ( TW ) . METHODS One hundred and twenty RA patients were r and omly assigned to two groups : the treated group treated with compound decoctum of TW and liquorice and the control group with TW ployglycosidium tablets both based on routine treatment . The therapeutic effect and adverse reaction were observed after 2 months of treatment . RESULTS The total efficacy rate was 89.8 % in the treated group and 79.6 % in the control group with insignificant difference between the two groups ; the effect was better in the treated group than that of the control group in decreasing the swollen joint index and increasing the average grip strength of both h and s ( P < 0.05 ) ; the total incidence of adverse reaction was obviously lower in the treated group than that of the control ( P < 0.01 ) . CONCLUSION Liquorice has toxicity attenuation and efficacy potentiation effect on treatment of RA with TW OBJECTIVE To observe the effect of Fengshi No. 1 ( FS1 ) in treating patients with active stage of rheumatoid arthritis ( RA ) . METHODS Patients with RA were r and omly divided into two groups , the 40 patients in the treated group were treated with combined therapy of methotrexate ( MTX ) , sulfasalazine ( SSZ ) and FS1 , and the 20 in the control groups were treated with MTX and SSZ alone . RESULTS In the treated group , the total effective rate was 97.5 % , the clinical controlled and markedly effective rate 95.0 % and the occurrence rate of side-toxic reaction 10.0 % , as compared with those in the control group , 60.0 % , 20.0 % and 45.0 % respectively , the difference was significant ( chi 2 = 11.91 , 32.23 and 7.67 respectively , all P < 0.01 ) . The effect in the treated group was superior to that in the control group in abating joint swelling and pain , improving function of joint , reducing immune indices and ameliorating iconographic features ( P < 0.01 or P < 0.05 ) . CONCLUSION FS1 not only has the effects of anti-inflammation , analgesis , regulating immune reaction , but also could retard the occurring of bone destruction , reduce the toxic-side effects of MTX and SSZ Objective To investigate the change of T-lymphocyte subsets in peripheral blood of rheumatoid arthritis ( RA ) patients and analyze the effects of Fuzheng Qubi Decoction ( FZQBD ) on T-cell subsets . Methods Thirty RA patients were r and omly divided into two groups , and treated with FZQBD or western medicine combination therapy respectively for one month , the percentage of peripheral CD3 + , CD4 + , CD8 + as well as the serum IgG and IgA levels were determined . Results The percentage of peripheral CD4 + , CD4 + /CD8 + ratio , IgG and IgA levels increased significantly ( p < 0.001 ) in RA patients before treatment . After 1 month of FZQBD treatment , the CD4 + /CD8 + ratio decreased obviously < 0.05 ) . Conclusion Abnormal cellular immunity exists in RA patients , FZQBD could adjust the abnormal T-lymphocyte subsets to normalize it OBJECTIVE To study the indication and clinical efficacy of Biqi capsule ( BC ) in treating patients with rheumatoid arthritis ( RA ) . METHODS One hundred and forty-two RA patients were r and omly divided into the BC treated group and the control group treated with nimesulide tablet ( NT ) . There were 36 patients with dampness-heat blockage syndrome type and 35 patients with Qi deficiency and blood stasis syndrome type in each group . The treatment course lasted for 8 weeks . RESULTS The total effective rate in the BC group was 66.2 % ( 47 cases ) , while that in the control group was 60.6 % ( 43 cases ) . The total effective rate in the patients with Qi deficiency and blood stasis syndrome type in the BC group was 91.4 % , superior to that with dampness-heat blockage type ( 41.7 % ) . Only one patient showed mild adverse reaction in the BC group . CONCLUSION BC is a kind of safe and effective herble medicine for treatment of RA , especially for those of Qi deficiency and blood stasis syndrome type |
12,138 | 28,542,317 | Multi-component strategies involving both upstream and downstream interventions , generally achieved the biggest reductions in salt consumption across an entire population , most notably 4g/day in Finl and and Japan , 3g/day in Turkey and 1.3g/day recently in the UK .
Worksite interventions achieved an increase in intake ( + 0.5g/day ) , however , with a very wide range .
Comprehensive strategies involving multiple components ( reformulation , food labelling and media campaigns ) and " upstream " population -wide policies such as m and atory reformulation generally appear to achieve larger reductions in population -wide salt consumption than " downstream " , individually focussed interventions . | BACKGROUND Non-communicable disease ( NCD ) prevention strategies now prioritise four major risk factors : food , tobacco , alcohol and physical activity .
Dietary salt intake remains much higher than recommended , increasing blood pressure , cardiovascular disease and stomach cancer .
Substantial reductions in salt intake are therefore urgently needed .
However , the debate continues about the most effective approaches .
To inform future prevention programmes , we systematic ally review ed the evidence on the effectiveness of possible salt reduction interventions .
We further compared " downstream , agentic " approaches targeting individuals with " upstream , structural " policy-based population strategies . | OBJECTIVE To examine whether a worksite nutrition programme using a low-fat vegan diet could significantly improve nutritional intake . DESIGN At two corporate sites of the Government Employees Insurance Company , employees who were either overweight ( BMI > or = 25 kg/m2 ) and /or had type 2 diabetes participated in a 22-week worksite-based dietary intervention study . SETTING At the intervention site , participants were asked to follow a low-fat vegan diet and participate in weekly group meetings that included instruction and group support ( intervention group ) . At the control site , participants received no instruction ( control group ) . At weeks 0 and 22 , participants completed 3 d dietary records to assess energy and nutrient intake . SUBJECTS A total of 109 participants ( sixty-five intervention and forty-four control ) . RESULTS In the intervention group , reported intake of total fat , trans fat , saturated fat and cholesterol decreased significantly ( P < or = 0.001 ) , as did energy and protein ( P = 0.01 ) , and vitamin B12 ( P = 0.002 ) , compared with the control group . Intake ( exclusive of any use of nutritional supplements ) of carbohydrate , fibre , vitamin C , magnesium and potassium increased significantly ( P < or = 0.0001 ) , as did that for beta-carotene ( P = 0.0004 ) , total vitamin A activity ( P = 0.004 ) , vitamin K ( P = 0.01 ) and sodium ( P = 0.04 ) in the intervention group , compared with the control group . CONCLUSIONS The present study suggests that a worksite vegan nutrition programme increases intakes of protective nutrients , such as fibre , folate and vitamin C , and decreases intakes of total fat , saturated fat and cholesterol BACKGROUND The beneficial effects of potassium-enriched salt on blood pressure have been reported in a few short-term trials . The long-term effects of potassium-enriched salt on cardiovascular mortality have not been carefully studied . OBJECTIVE The objective was to examine the effects of potassium-enriched salt on cardiovascular disease ( CVD ) mortality and medical expenditures in elderly veterans . DESIGN Five kitchens of a veteran retirement home were r and omized into 2 groups ( experimental or control ) and veterans assigned to those kitchens were given either potassium-enriched salt ( experimental group ) or regular salt ( control group ) for approximately 31 mo . Information on death , health insurance cl aims , and date s that veterans moved in or out of the home was gathered . RESULTS Altogether , 1981 veterans , 768 in the experimental [ x ( + /-SD ) age : 74.8 + /- 7.1 y ] and 1213 in the control ( age : 74.9 + /- 6.7 y ) groups , were included in the analysis . The experimental group had better CVD survivorship than did the control group . The incidence of CVD-related deaths was 13.1 per 1000 persons ( 27 deaths in 2057 person-years ) and 20.5 per 1000 ( 66 deaths in 3218 person-years ) for the experimental and control groups , respectively . A significant reduction in CVD mortality ( age-adjusted hazard ratio : 0.59 ; 95 % CI : 0.37 , 0.95 ) was observed in the experimental group . Persons in the experimental group lived 0.3 - 0.90 y longer and spent significantly less ( approximately US Dollars 426/y ) in inpatient care for CVD than did the control group , after control for age and previous hospitalization expenditures . CONCLUSIONS This study showed a long-term beneficial effect on CVD mortality and medical expenditure associated with a switch from regular salt to potassium-enriched salt in a group of elderly veterans . The effect was likely due to a major increase in potassium and a moderate reduction in sodium intakes BACKGROUND Sodium intake is high in people with type 2 diabetes ( T2DM ) . The aim of this study was to investigate whether urinary sodium excretion can be reduced by educating people with T2DM to read food labels and choose low sodium products . METHOD In a 3 month r and omised controlled trial , 78 men ( n=49 ) and women ( n=29 ) with T2DM were recruited from a Diabetes Centre at a University teaching hospital . The intervention group was educated in a single session to use the nutrition information panel on food labels to choose products which complied with the Food St and ards Australia New Zeal and ( FSANZ ) guideline of < 120 mg sodium/100 g food . The control group continued on their usual diet . The primary outcome measure was 24h urinary sodium excretion which was performed at baseline and 3 months . Data was analysed using repeated measures analysis of variance , independent sample s t-test and Pearson 's correlations . RESULTS At 3 months mean urinary sodium excretion was unchanged in the intervention ( 174±13 mmol/24 h and 175±13 mmol/24 h ) and control group ( 167±15mmol/24h and 161±13 mmol/24 h ) , and there was no between group difference ( p>0.05 ) . CONCLUSION Sodium excretion was not reduced following the label reading education provided to this group of people with T2DM The aim of this study is to examine sodium intake and dietary sodium sources of 1‐5‐y‐old children in a prospect i ve , r and omized long‐term coronary heart disease prevention trial , focused on dietary fat modification . Counselling included no advice about reducing salt in the children 's diets . Food consumption of 100 intervention children and 100 control children was recorded for 3 consecutive days at the age of 13 mo and for 4 consecutive days at the ages of 3 and 5 y. Sodium intakes were calculated using the Micro Nutrica program . Children 's mean daily sodium ( NaCl ) consumption ( intervention and control children combined ) was 1600 ± 527 mg ( 4.0 ± 1.3 g ) , 1900 ± 504 mg ( 4.8 ± 1.3 g ) and 2200 ± 531 mg ( 5.5 ± 1.3 g ) at the ages of 13 mo and 3 and 5 y , respectively . The intervention children consumed as much or slightly more sodium than the control children at all ages studied . Half the sodium consumption was derived from added salt in commercially prepared or homemade foods . Milk , meat products , bread and cereals were other important sodium sources Objectives To assess geographic and socioeconomic gradients in sodium and potassium intake in Italy . Setting Cross-sectional survey in Italy . Participants 3857 men and women , aged 39–79 years , r and omly sample d in 20 regions ( as part of a National cardiovascular survey of 8714 men and women ) . Primary outcome measures Participants ’ dietary sodium and potassium intakes were measured by 24 h urinary sodium and potassium excretions . 2 indicators measured socioeconomic status : education and occupation . Bayesian geoadditive models were used to assess spatial and socioeconomic patterns of sodium and potassium intakes accounting for sociodemographic , anthropometric and behavioural confounders . Results There was a significant north-south pattern of sodium excretion in Italy . Participants living in southern Italy ( eg , Calabria , Basilicata and Puglia > 180 mmol/24 h ) had a significantly higher sodium excretion than elsewhere ( eg , Val d'Aosta and Trentino-Alto Adige < 140 mmol/24 h ; p<0.001 ) . There was a linear association between occupation and sodium excretion ( p<0.001 ) . When compared with occupation I ( top managerial ) , occupations III and IV had a 6.5 % higher sodium excretion ( coefficients : 0.054 ( 90 % credible levels 0.014 , 0.093 ) and 0.064 ( 0.024 , 0.104 ) , respectively ) . A similar relationship was found between educational attainment and sodium excretion ( p<0.0001 ) . When compared with those with a university degree , participants with primary and junior school education had a 5.9 % higher urinary sodium ( coefficients : 0.074 ( 0.031 , 0.116 ) and 0.038 ( 0.001 , 0.075 ) , respectively ) . The socioeconomic gradient explained the spatial variation . Potassium excretion was higher in central regions and in some southern regions . Those in occupation V ( low-skill workers ) showed a 3 % lower potassium excretion compared with those in occupation I. However , the socioeconomic gradient only partially explained the spatial variation . Conclusions Salt intake in Italy is significantly higher in less advantaged social groups . This gradient is independent of confounders and explains the geographical variation Background In Africa hypertension is common and stroke is increasing . Detection , treatment and control of high blood pressure ( BP ) is limited . BP can be lowered by reducing salt intake . In Africa salt is added to the food by the consumer , as processed food is rare . A population -wide approach with programmes based on health education and promotion is thus possible . Methods We carried out a community-based cluster r and omised trial of health promotion in 1,013 participants from 12 villages ( 628 women , 481 rural dwellers ) ; mean age 55 years to reduce salt intake and BP . Average BP was 125/74 mmHg and urinary sodium ( UNa ) 101 mmol/day . A health promotion intervention was provided over 6 months to all villages . Assessment s were made at 3 and 6 months . Primary end-points were urinary sodium excretion and BP levels . Results There was a significant positive relationship between salt intake and both systolic ( 2.17 mmHg [ 95 % CI 0.44 to 3.91 ] per 50 mmol of UNa per day , p < 0.001 ) and diastolic BP ( 1.10 mmHg [ 0.08 to 1.94 ] , p < 0.001 ) at baseline . At six months the intervention group showed a reduction in systolic ( 2.54 mmHg [ -1.45 to 6.54 ] ) and diastolic ( 3.95 mmHg [ 0.78 to 7.11 ] , p = 0.015 ) BP when compared to control . There was no significant change in UNa . Smaller villages showed greater reductions in UNa than larger villages ( p = 0.042 ) . Irrespective of r and omisation , there was a consistent and significant relationship between change in UNa and change in systolic BP , when adjusted for confounders . A difference in 24-hour UNa of 50 mmol was associated with a lower systolic BP of 2.12 mmHg ( 1.03 to 3.21 ) at 3 months and 1.34 mmHg ( 0.08 to 2.60 ) at 6 months ( both p < 0.001 ) . Conclusion In West Africa the lower the salt intake , the lower the BP . It would appear that a reduction in the average salt intake in the whole community may lead to a small but significant reduction in population systolic BP Objectives To determine the relationship between the reduction in salt intake that occurred in Engl and , and blood pressure ( BP ) , as well as mortality from stroke and ischaemic heart disease ( IHD ) . Design Analysis of the data from the Health Survey for Engl and . Setting and participants Engl and , 2003 N=9183 , 2006 N=8762 , 2008 N=8974 and 2011 N=4753 , aged ≥16 years . Outcomes BP , stroke and IHD mortality . Results From 2003 to 2011 , there was a decrease in mortality from stroke by 42 % ( p<0.001 ) and IHD by 40 % ( p<0.001 ) . In parallel , there was a fall in BP of 3.0±0.33/1.4±0.20 mm Hg ( p<0.001/p<0.001 ) , a decrease of 0.4±0.02 mmol/L ( p<0.001 ) in cholesterol , a reduction in smoking prevalence from 19 % to 14 % ( p<0.001 ) , an increase in fruit and vegetable consumption ( 0.2±0.05 portion/day , p<0.001 ) and an increase in body mass index ( BMI ; 0.5±0.09 kg/m2 , p<0.001 ) . Salt intake , as measured by 24 h urinary sodium , decreased by 1.4 g/day ( p<0.01 ) . It is likely that all of these factors ( with the exception of BMI ) , along with improvements in the treatments of BP , cholesterol and cardiovascular disease , contributed to the falls in stroke and IHD mortality . In individuals who were not on antihypertensive medication , there was a fall in BP of 2.7±0.34/1.1±0.23 mm Hg ( p<0.001/p<0.001 ) after adjusting for age , sex , ethnic group , education , household income , alcohol consumption , fruit and vegetable intake and BMI . Although salt intake was not measured in these participants , the fact that the average salt intake in a r and om sample of the population fell by 15 % during the same period suggests that the falls in BP would be largely attributable to the reduction in salt intake rather than antihypertensive medications . Conclusions The reduction in salt intake is likely to be an important contributor to the falls in BP from 2003 to 2011 in Engl and . As a result , it would have contributed substantially to the decreases in stroke and IHD mortality Background The adoption and maintenance of healthy behaviours is essential in the primary prevention of chronic non-communicable diseases . This study evaluated the effectiveness of a minimal intervention on multiple lifestyle factors such as diet , physical activity , smoking and alcohol , delivered through general practice , using computer-tailored feedback . Methods Adult patients visiting 21 general practitioners in Brisbane , Australia , were surveyed about ten health behaviours that are risk factors for chronic , non-communicable diseases . Those who completed the self-administered baseline question naire entered a r and omised controlled trial , with the intervention group receiving computer-tailored printed advice , targeting those health behaviours for which respondents were not meeting current recommendations . The primary outcome was change in summary lifestyle score ( Prudence Score ) and individual health behaviours at three months . A repeated measures analysis compared change in these outcomes in intervention and control groups after adjusting for age and education . Results 2306 patients were r and omised into the trial . 1711 ( 76 % ) returned the follow-up question naire at 3 months . The Prudence Score ( 10 items ) in the intervention group at baseline was 5.88 , improving to 6.25 at 3 months ( improvement = 0.37 ) , compared with 5.84 to 5.96 ( improvement = 0.12 ) in the control group ( F = 13.3 , p = 0.01 ) . The intervention group showed improvement in meeting recommendations for all individual health behaviours compared with the control group . However , these differences were significant only for fish intake ( OR 1.37 , 95 % CI 1.11 - 1.68 ) , salt intake ( OR 1.19 , 95 % CI 1.05 - 1.38 ) , and type of spread used ( OR 1.28 , 95 % CI 1.06 - 1.51 ) . Conclusion A minimal intervention using computer-tailored feedback to address multiple lifestyle behaviours can facilitate change and improve unhealthy behaviours . Although individual behaviour changes were modest , when implemented on a large scale through general practice , this intervention appears to be an effective and practical tool for population -wide primary prevention . Trial Registration The Australian New Zeal and Clinical Trials Registry : In Finl and since the 1980s , coronary heart disease mortality has declined more than might be predicted by risk factor reductions alone . The aim of this study was to assess how much of the decline could be attributed to improved treatments and risk factor reductions . The authors used the cell-based IMPACT mortality model to synthesize effectiveness of treatments and risk factor reductions with data on treatments administered to patients and trends in cardiovascular risk factors in the population . Cardiovascular risk factors were measured in r and om sample s of patients in 1982 ( n=8,501 ) and 1997 ( n=4,500 ) . Mortality and treatment data were obtained from the National Causes of Death Register , Hospital Discharge Register , social insurance data , and medical records . Estimated and observed changes in coronary heart disease mortality were used as main outcome measures . Between 1982 and 1997 , coronary heart disease mortality rates declined by 63 % , with 373 fewer deaths in 1997 than expected from baseline mortality rates in 1982 . Improved treatments explained approximately 23 % of the mortality reduction , and risk factors explained some 53 - 72 % of the reduction . These findings highlight the value of a comprehensive strategy that promotes primary prevention programs and actively supports secondary prevention . It also emphasizes the importance of maximizing population coverage of effective treatments Objective . The authors tested the impact on cardiovascular risk profiles of African American women ages 40 years and older after one year of participation in one of three church-based nutrition and physical activity strategies : a st and ard behavioral group intervention , the st and ard intervention supplemented with spiritual strategies , or self-help strategies . Methods . Women were screened at baseline and after one year of participation . The authors analyzed intention-to-treat within group and between groups using a generalized estimating equations adjustment for intra-church clustering . Because spiritual strategies were added to the st and ard intervention by participants themselves , the results from both active groups were similar and , thus , combined for comparisons with the self-help group . Results . A total of 529 women from 16 churches enrolled . Intervention participants exhibited significant improvements in body weight ( −1.1 lbs ) , waist circumference ( −0.66 inches ) , systolic blood pressure ( −1.6 mmHg ) , dietary energy ( −117 kcal ) , dietary total fat ( −8 g ) , and sodium intake ( −145 mg ) . The self-help group did not . In the active intervention group , women in the top decile for weight loss at one year had even larger , clinical ly meaningful changes in risk outcomes ( −19.8 lbs ) . Conclusions . Intervention participants achieved clinical ly important improvements in cardiovascular disease risk profiles one year after program initiation , which did not occur in the self-help group . Church-based interventions can significantly benefit the cardiovascular health of African American women Objective : This study determined the behavioral and clinical impact of a worksite chronic disease prevention program . Methods : Working adults participated in r and omized clinical trial of an intensive lifestyle intervention . Nutrition and physical activity behavior and several chronic disease risk factors were assessed at baseline , 6 weeks , and 6 months . Results : Cognitive underst and ing of the requirements for a healthy lifestyle increased at the end of the program . Program participants significantly improved their cognitive underst and ing of good nutrition and physical activity and had significantly better nutrition and physical activity behavior at both 6 weeks and 6 months . Participants had significantly lower body fat , blood pressure , and cholesterol . Conclusions : This worksite chronic disease prevention program can significantly increase health knowledge , can improve nutrition and physical activity , and can improve many employee health risks in the short term Objective : High sodium intake increases the risk of cardiovascular diseases and may also be associated with higher rates of stomach cancer , asthma disorders and infections . In Finl and , cross-sectional population surveys to monitor cardiovascular risk factors have been carried out since the 1970s . The main aim of this paper is to present trends in urinary sodium and potassium excretion from 1979 to 2002 . Design : Cross-sectional population surveys on cardiovascular risk factors . Setting : Surveys were carried out in Finl and in 1979 , 1982 , 1987 and 2002 in four geographical areas : North Karelia , the Kuopio area , Southwestern Finl and and the Helsinki area . Subjects : For each survey a r and om sample stratified by age and sex was drawn from the population register . In this analysis , participants of urine collection sub sample s aged 25–64 years ( n=4648 ) were included . Interventions : A 24-h urinary collection was carried out in sub sample s ( n=2218–2487 ) in connection with population risk factor surveys . Urinary sodium and potassium concentrations were analyzed in the same laboratory throughout , using a flame photometer in 1979 , 1982 and 1987 and an ion-selective electrode in 2002 . Results : Between 1979 and 2002 urinary sodium excretion in Finl and decreased from over 220 to less than 170 mmol/day among men and from nearly 180 to less than 130 mmol/day among women . Although potassium excretion decreased somewhat as well , the decrease in sodium – potassium molar ratio was also significant . Conclusions : The 24-h urinary sodium excretion in Finl and has decreased significantly during the last 20 years . However , excretion levels are still considerably higher than recommendations . A further decrease in sodium intake remains a goal for the Finnish food industry and consumers . Sponsorship : All surveys were funded by the National Public Health Institute in Finl and There is still a need of support for nonpharmacologic treatment of uncomplicated , mild-to-moderate essential hypertension . We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity . Middle-aged , otherwise healthy men with never-treated essential hypertension ( n = 95 ) were r and omized to an intervention group , a blood pressure control group , and a time control group . The intervention group was advised to use less sodium chloride in their diet , and if necessary , less saturated fat and decrease body weight . They attended regular clinic visits as did the blood pressure control group . After 1 year , the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion ( P < .001 ) and a decrease in body weight of 2.7 + /- 0.5 kg ( P < .001 ) . Both supine and st and ing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups ( P < .001 ) . Arterial plasma epinephrine , measured in all 40-year-old subjects ( n = 30 ) , decreased in parallel in all three groups ( P < .05 ) , indicating some habituation to the invasive procedure and clinic visits . However , the decrease in norepinephrine was significant ( P < .001 ) only in the intervention group ; it correlated with the weight loss ( r = 0.76 , P < .05 ) and was significantly higher ( P < .05 ) than in both control groups . These results suggest that broad dietary advice ( ie , low intake of sodium chloride , saturated fat and energy ) , implemented by a nutritionist , may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated , mild-to-moderate essential hypertension BACKGROUND High salt and nitrate intake are considered as risk factors for stomach cancer , but little is known about possible interactions . This ecological study examines the respective importance of both factors for stomach cancer mortality at the population level using data obtained under st and ardized conditions and with biochemical analyses performed in the same laboratories . METHODS R and omly selected 24-hour urine sample s from 39 population s , sample d from 24 countries ( N = 5756 people for sodium , 3303 for nitrate ) were obtained from the INTERSALT study . Median sodium and nitrate levels were age- and sex-st and ardized between ages 20 - 49 years and averaged per country . Ecological correlation-regression analyses were done in relation to national stomach cancer mortality rates . RESULTS The Pearson correlation of stomach cancer mortality with sodium for the 24 countries was : 0.70 in men and 0.74 in women ( both P < 0.001 ) and with nitrate : 0.63 ( P = 0.001 ) in men and ( P < 0.005 ) in women . In multiple regression of stomach cancer mortality , using sodium and nitrate as independent variables the adjusted R2 was 0.61 in men and 0.54 in women ( both P < 0.001 ) . Addition of the interaction term ( sodium x nitrate ) to the previous model increased the adjusted R2 to 0.77 in men , and to 0.63 in women . The analysis of this model showed that the importance of nitrate as risk factor for stomach cancer mortality increased markedly with higher sodium levels . However , the relationship of stomach cancer mortality with sodium was always stronger than with nitrate . CONCLUSIONS Salt intake , measured as 24-hour urine sodium excretion , is likely the rate-limiting factor of stomach cancer mortality at the population level OBJECTIVE Evaluation of a dietary Na reduction trial in a community setting . DESIGN Community-based r and omized trial . Ten-week nutrition intervention activities focused on lifestyle modification to decrease dietary Na intake , under the supervision of a registered dietitian . Twenty-four hour urine specimens were collected at baseline and follow-up visits to determine 24 h urinary Na excretion . SETTING The University of Pittsburgh Center for Healthy Aging , Key to Life Nutrition Program . SUBJECTS Hypertensive adults at least 65 years of age . RESULTS Mean age of participants was 75 years . Twenty-four hour mean urinary Na excretion at baseline was 3174 mg/d . This reduced to 2944 mg/d ( P = 0.30 ) and 2875 mg/d ( P < or= 0.03 ) at 6- and 12-month follow-ups , respectively . In a sub- sample ( urine volume of > or=1000 ml , baseline to 12 months ) , mean urinary Na excretion decreased from 3220 mg/d to 2875 mg/d ( P < or= 0.02 ) . CONCLUSIONS Significant reductions in mean 24 h urinary Na were reported , but results fell short of the recommended guidelines of 1500 mg/d for at-risk individuals . Our results reiterate the difficulty in implementing these guidelines in community-based programmes . More aggressive public health efforts , food industry support and health policy changes are needed to decrease Na levels in older adults to the recommended guidelines Objective To assess whether dietary intervention in free-living healthy subjects is effective in improving blood pressure levels . Design Open r and omised , controlled trial . Setting Free-living healthy subjects in two rural villages in north-eastern Japan . Participants Five hundred and fifty healthy volunteers aged 40–69 years . Interventions Tailored dietary education to encourage a decrease in sodium intake and an increase in the intake of vitamin C and carotene , and of fruit and vegetables . Main outcome measures Blood pressure , dietary intake and urinary excretion of sodium , dietary carotene and vitamin C , and fruit and vegetable intake data were collected at 1 year after the start of the intervention . Results During the first year , changes differed significantly between the intervention and control groups for dietary ( P = 0.002 ) and urinary excretion ( P < 0.001 ) of sodium and dietary vitamin C and carotene ( P = 0.003 ) . Systolic blood pressure decreased from 127.9 to 125.2 mmHg ( 2.7 mmHg decrease ; 95 % confidence interval , −4.6 to −0.8 ) in the intervention group , whereas it increased from 128.0 to 128.5 mmHg ( 0.5 increase ; −1.3 to 2.3 ) in the control group . This change was statistically significant ( P = 0.007 ) . In contrast , the change in diastolic blood pressure did not significantly differ between the groups . In hypertensive subjects , a significant difference in systolic blood pressure reduction was seen between the groups ( P = 0.032 ) . Conclusion Moderate-intensity dietary counseling in free-living healthy subjects achieved significant dietary changes , which result ed in a significant decrease in systolic blood pressure OBJECTIVE To compare , in adolescents , two models of front-of-pack Guideline Daily Amounts ( GDA ) labels in terms of ( i ) friendliness and acceptance and ( ii ) the ability to choose a diet that closely follows the nutritional recommendations . DESIGN A r and omized cross-over study was design ed to compare two simplified front-of-pack GDA nutrition labels . SETTING A Spanish secondary school . SUBJECTS Eighty-one healthy adolescents aged between 14 and 16 years were recruited . Participants were r and omly exposed to two experimental non-real food-choice conditions using multiple-traffic-light or monochrome nutritional labels . Participants had to choose options from a closed menu for 5 d on the basis of the experimental front-of-pack labelling . For each meal , three food options with different nutritional compositions were given to the participants . The contents of total energy and fat , saturated fat , sugar and salt of the chosen options were calculated . RESULTS There were no significant differences in baseline sociodemographic and anthropometric characteristics between participants regardless of the experimental condition in which they started . There were no carry-over effects between the experimental sequences . It was observed that when participants used the multiple-traffic-light GDA system they chose significantly less total energy ( mean -123·1 ( sd 211·0 ) kJ ( -29·4 ( sd 50·4 ) kcal ) , P < 0·001 ) , sugar ( -4·5 ( sd 4·6 ) g , P < 0·001 ) , fat ( -2·1 ( sd 4·5 ) g , P = 0·006 ) , saturated fat ( -1·0 ( sd 1·9 ) g , P = 0·002 ) and salt ( -0·4 ( sd 0·5 ) g , P < 0·001 ) than when they used the monochrome GDA system . CONCLUSIONS Compared with the monochrome GDA front-of-pack nutritional label , the multiple-traffic-light system helped adolescents to differentiate between healthier and less healthy food , theoretically making it possible for them to choose a diet closer to dietary recommendations |
12,139 | 11,856,775 | There was no effect of L-carnitine on triglycerides , total cholesterol , or any of its fractions .
In conclusion , L-carnitine can not be recommended for treating the dyslipidemia of maintenance hemodialysis patients .
By contrast , this review suggests a promising effect of L-carnitine on anemia management . | There are many causes for carnitine depletion during maintenance hemodialysis .
Supplementation with L-carnitine in animals has been associated with improvement in some abnormalities also present in chronic renal failure .
However , it is still controversial whether restoring plasma or tissue carnitine will correct clinical or biologic symptoms observed in maintenance hemodialysis .
A systematic review is here performed to determine the effects of L-carnitine in maintenance hemodialysis patients . | Since carnitine deficiency has been reported in some patients undergoing maintenance hemodialysis , we studied the effects of intravenous infusion of L-carnitine or placebo at the end of each dialysis treatment . The trial , which lasted seven months ( one month baseline , 6 months treatment ) was multicenter , double blind , placebo controlled , and r and omized . Eighty-two long-term hemodialysis patients , who were given either carnitine ( N = 38 ) or placebo ( N = 44 ) , completed this study . In each group , clinical and biochemical parameters during treatment were compared with baseline values . Intra-dialytic hypotension and muscle cramps were reduced only in the carnitine treated group , while improvement in post-dialysis asthenia was noticed in both carnitine and placebo groups . Maximal oxygen consumption , measured during a progressive work exercise test , improved significantly in the carnitine group ( 111 + /- 50 ml/min . P less than 0.03 ) and was unchanged in the placebo group . L-carnitine treatment was associated with a significant drop in pre-dialysis concentrations of serum urea nitrogen , creatinine and phosphorus ( means + /- SEM , 101 + /- 4.5 to 84 + /- 3.9 , 16.7 + /- 0.67 to 14.7 + /- 0.64 , and 6.4 + /- 0.3 to 5.5 + /- 0.4 mg/dl , respectively , P less than 0.004 ) . No significant changes in any of these variables were noticed in the placebo group . Mid-arm circumference and triceps skinfold thickness were measured in 11 carnitine and 13 placebo treated patients . Calculated mid-arm muscle area increased in the carnitine patients ( 41.37 + /- 2.68 to 45.6 + /- 2.82 cm2 , P = 0.05 ) and remained unchanged in the placebo patients . ( ABSTRACT TRUNCATED AT 250 WORDS It has been reported that treatment with L-carnitine at a daily dose of 3 g orally may cause a rise in platelet aggregation and serum triglyceride concentration in hemodialyzed patients . The present double-blind cross-over study has been performed to evaluate the influence of L-carnitine when compared with placebo on platelet aggregation and plasma concentrations of various factors involved in platelet activation . In addition , the concentration of triglycerides , cholesterol and HDL-cholesterol has been evaluated . 18 uremic patients on maintenance hemodialysis for at least 1 year were r and omly allocated either to a control group receiving placebo or to a group treated with L-carnitine . Statistical analysis performed by means of ANOVA did not show any significant change in the serum concentration of cholesterol , HDL-cholesterol and triglycerides . Furthermore , platelet aggregation tests ( performed with adenosine 5'-diphosphate , epinephrine , thrombin and collagen ) and plasma beta-thromboglobulin concentration did not show any statistically significant difference . In addition , the plasma concentration of several coagulation markers , such as factor VIIIc , antithrombin III , alpha 2-antiplasmin , and fibrinopeptide A , did not show any significant variation . The results suggest that under our experimental conditions L-carnitine neither increases the risk of thromboembolism nor alters the serum lipid content in uremic patients on chronic hemodialysis Hypertriglyceridemia is often present in chronically uremic patients treated with maintenance hemodialysis and has been considered a risk factor in the accelerated development of atheroma . Muscle carnitine content is low in hemodialyzed patients . This abnormality may help to explain the myopathy and cardiomyopathy often observed in these subjects . In addition , carnitine might play a role in the hypertriglyceridemia in renal failure . Carnitine , which is necessary for fatty acid oxidation , has been recently reported to lower serum triglycerides in patients with type IV hyperlipoproteinemia . Carnitine was administered intravenously three times weekly at the end of hemodialysis in eight patients . Carnitine was given in 0.5 g doses for 8 weeks and then in 1.0 g doses for 6 additional weeks . There was a significant decrease in serum triglycerides at the end of treatment . In contrast , serum lipids in eight hemodialysis patients receiving placebo did not change significantly . Carnitine administration does not cause any side effect except some euphoria . These results suggest that carnitine may be effective in the treatment of hypertriglyceridemia in dialysis patients A group of 14 uremic patients on intermittent hemodialysis was admitted to a cross-over double-blind trial in order to evaluate serum and muscle carnitine levels before and after 60 days of L-carnitine oral ( 2 g/day ) treatment . The morphology of muscle fragments was studied by light and electron microscopy . Symptoms ( asthenia , cramps ) occurring during hemodialysis were also recorded . After L-carnitine treatment the blood and muscle levels of the metabolite increased simultaneously to reduced asthenia and cramps . Morphological examination of the muscle of 13 of 14 patients did not reveal any pre- or posttreatment pathological alterations . The presence of nemaline rods was morphologically diagnosed in only one case and was no longer observed at the second biopsy at 2 months of L-carnitine treatment Left ventricular function was non-invasively studied in 28 r and omly selected haemodialysis patients before and after administration of L-carnitine , 2 g i.v . three times per week or saline in a double blind design ed study over a six-week period . Cardiac function variables showed no relationship to muscle ( vastus lateralis ) and plasma carnitine concentrations . No apparent deficiency in muscle carnitine was found , whereas total plasma carnitine was lower in female patients than in female controls , p less than 0.002 . The echocardiographic left ventricular end-diastolic diameter was initially increased in about one third and the ejection fraction was depressed in about one fifth of the patients . An increased A : H ratio was found in 15 % . Systolic time intervals were deranged in 30 % of the patients . After carnitine administration , marked increases of muscle and plasma carnitine levels were found , p less than 0.01 , but no effects were recorded in any of the cardiac tests . Muscle carnitine increased from 14.6 mmol/kg dry weight to a median of 23.7 mmol/kg . We found no support for the hypothesis that carnitine depletion is responsible for cardiac dysfunction in haemodialysis patients Previous studies have reported conflicting results of carnitine supplementation on plasma lipids in patients with chronic renal failure . We therefore performed a four center , double-blind placebo controlled trial to evaluate the effects of post-hemodialysis intravenous injection of L-carnitine in ESRD patients on maintenance hemodialysis . Thirty-eight patients received up to six months of L-carnitine infusions ( 20 mg/kg ) post-dialysis and 44 patients received placebo infusions . In both groups of patients , baseline pre-dialysis plasma and red blood cell total carnitine levels were normal , but pre-dialysis plasma-free carnitine concentrations and free/total ratios were subnormal , and plasma acyl levels were elevated . Post-dialysis plasma free and total carnitine concentrations were also subnormal . Plasma and red blood cell total carnitine levels rose eightfold in carnitine recipients , but were unchanged from baseline in those receiving placebo . There were no significant changes observed in plasma triglycerides , HDL-cholesterol or other lipoprotein parameters in either the carnitine or placebo treated groups . We conclude that carnitine metabolism is altered in uremia . Furthermore , in a r and omly-selected hemodialysis population , L-carnitine injection at the dose of 20 mg/kg results in significant increases in blood ( and perhaps tissue ) carnitine levels , but this is not associated with any major effects on lipid profiles End-stage renal disease affects every aspect of a patient 's life , including perception of health and quality of life . It is likely that a hemodialysis patient 's perceptions of health-related quality of life directly influence compliance with medical , nursing , and nutritional prescriptions . Because L-carnitine supplementation is known to enhance muscle strength and energy in hemodialysis patients , we hypothesized that L-carnitine supplementation would enhance a hemodialysis patient 's perception of health-related quality of life . To test this hypothesis , 1 g L-carnitine or placebo was administered orally to 101 patients immediately before and after every hemodialysis treatment for 6 months . To assess health-related quality of life from the patient 's perspective , the Medical Outcomes Study Short Form 36 instrument was administered before the study and at 1.5-month intervals for the duration of the study . In addition , a 10-item question naire design ed to assess common intradialytic symptoms was administered at the end of each dialysis treatment . Other parameters analyzed included Kt/V(urea ) and level of nutrition . In the 6-month group , oral L-carnitine supplementation had an early positive effect on general health ( P < 0.02 ) and physical function ( P < 0.03 ) , but the perceived effect was not sustained throughout the 6 months of the study . In the 3-month group , L-carnitine supplementation improved vitality ( P < 0.02 ) and general health ( P < 0.01 ) . There was no association between Kt/V(urea ) and perceived health-related quality of life . Serum albumin concentration was directly correlated to how patients perceived the quality of their lives Carnitine supplementation in hemodialyzed patients was studied in a double-blinded , r and omized , controlled trial in order to eluci date the effect of intravenous carnitine on renal anemia in patients treated with recombinant human erythropoietin ( rHuEPO ) . Twenty stable hemodialysis ( HD ) patients received intravenous L-carnitine after each dialysis session in a dosage of 5 ( N = 15 ) and 25 ( N = 5 ) mg/kg , respectively , together with intravenous iron saccharate ( 20 mg/HD session ) for four months and without iron for a further four months . Twenty patients received placebo instead of carnitine with an identical iron regimen . After a run-in phase of six months with a stable rHuEPO requirement , the rHuEPO dose was adjusted monthly when necessary to maintain target hemoglobin levels . At study entry ( T0 ) , plasma and red blood cell carnitine levels did not correlate significantly with the rHuEPO requirement . However , plasma free and total carnitine levels showed a significant negative correlation with erythrocyte survival time at T0 . After four months of coadministration of intravenous iron and L-carnitine ( T4 ) , the rHuEPO requirement decreased in 8 of 19 evaluable HD patients . In these responders , the weekly rHuEPO dose was decreased significantly by 36.9+/-23.3 % ( 183.7+/-131.7 at T0 vs. 126.6+/-127.9 U/kg/week at T4 , P < 0.001 ) . The rHuEPO requirement , however , was unchanged when all carnitine-treated patients were compared between T0 and T4 ( T0 : 172.0+/-118.0 vs. T4 : 152.3+/-118.8 U/kg/week , P = 0.07 , NS ) , but the erythropoietin resistance index decreased significantly in this group ( T0 : 16.0+/-11.0 vs. T4 : 13.6+/-10.5 U/kg/week/g of hemoglobin , P < 0.02 ) . The erythrocyte survival time was measured in five HD patients treated with iron and carnitine at T0 and T4 . Two out of these patients were carnitine responders and showed an increase of erythrocyte survival time of 15 and 20 % , respectively . After the withdrawal of iron supplementation , the rHuEPO requirement increased comparably in both L-carnitine- and placebo-treated patients during four more months . According to our data , L-carnitine , in addition to iron supplementation , may have an effect on erythropoietin resistance and erythrocyte survival time in HD patients . More than half of our patients , however , showed no benefit . Further studies to identify those HD patients who might have a benefit of carnitine supplementation , as well as studies concerning the optimal dosage , duration , and way of administration of carnitine supplementation and its mechanism of action , are required In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies To demonstrate whether L-carnitine treatment could further improve the anemia in dialyzed patients under recombinant human erythropoietin ( r-HuEPO ) therapy , leading to a reduction in r-HuEPO requirements , L-carnitine ( 1 g intravenously after every dialysis session ) was administered for 6 months to a group of 13 patients ; the results were compared with data from a placebo control group ( N = 11 ) . Globular osmotic fragility and endogenous EPO secretion were also evaluated . L-Carnitine treatment promoted a 38.1 % reduction in r-HuEPO requirements in the active group ( 102.2 + /- 52.6 U/kg/wk v 63.3 + /- 37.8 U/kg/wk ; P < 0.02 ) , with globular osmotic fragility and endogenous EPO levels remaining unchanged and thus not accounting for carnitine effect on anemia . In the active group , seven patients decreased r-HuEPO needs ( responders ) , while six did not ( nonresponders ) . Compared with nonresponders , responders showed higher mean values at time 0 for r-HuEPO requirements and endogenous plasma EPO levels , although not statistically significant . It is concluded that L-carnitine deficiency might promote EPO resistance in dialyzed patients , which is corrected by L-carnitine supplementation , ultimately reducing r-HuEPO requirements Uremic patients undergoing chronic hemodialysis demonstrate a secondary systemic carnitine deficiency . We studied the effect of carnitine replacement with high doses ( L-carnitine , 3 g/day ) similar to those used in the treatment of primary systemic carnitine deficiency . 10 uremic patients on hemodialysis were r and omly selected into a control group ( 4 patients ) treated by placebo and a treatment group ( 6 patients ) treated by L-carnitine . Plasma lipoprotein concentration and composition as well as platelet aggregation were studied before and after treatment . Following carnitine administration , a paradoxical rise in plasma triglyceride concentration from 180 + /- 66 to 219 + /- 88 mg% ( p less than 0.05 ) was noted . No other significant changes in lipoprotein concentration and composition or in plasma apoprotein A-I and B concentration were observed . Carnitine treatment caused a significant rise in platelet aggregation induced by epinephrine , ADP , and thrombin . These findings suggest a harmful effect of L-carnitine replacement therapy when given in high doses , causing aggravation of uremic hypertriglyceridemia and increased platelet aggregation in patients predisposed to thromboembolic phenomena |
12,140 | 21,520,288 | Most positive effects were found in caregivers of people with a diagnosis of ' dementia not otherwise specified ' and in the subgroup of female caregivers .
Examples of outcomes were decreased depression and improved self-efficacy .
CONCLUSIONS This study gives a first overview of successful psychosocial interventions in subgroups of caregivers of people with dementia . | OBJECTIVE Insight into the characteristics of caregivers for whom psychosocial interventions are effective is important for care practice .
Until now no systematic review s were conducted into the effectiveness of psychosocial interventions for caregiver subgroups .
METHODS To gain insight into this relationship between caregiver subgroups and intervention outcomes , a first review study was done .
This study review s the personal characteristics of caregivers of people with dementia for whom psychosocial interventions were effective . | OBJECTIVE To determine the effectiveness of community based occupational therapy on daily functioning of patients with dementia and the sense of competence of their care givers . DESIGN Single blind r and omised controlled trial . Assessors were blinded for treatment allocation . SETTING Memory clinic and day clinic of a geriatrics department and participants ' homes . PARTICIPANTS 135 patients aged > or = 65 with mild to moderate dementia living in the community and their primary care givers . INTERVENTIONS 10 sessions of occupational therapy over five weeks , including cognitive and behavioural interventions , to train patients in the use of aids to compensate for cognitive decline and care givers in coping behaviours and supervision . MAIN OUTCOME MEASURES Patients ' daily functioning assessed with the assessment of motor and process skills ( AMPS ) and the performance scale of the interview of deterioration in daily activities in dementia ( IDDD ) . Care giver burden assessed with the sense of competence question naire ( SCQ ) . Participants were evaluated at baseline , six weeks , and three months . RESULTS Scores improved significantly relative to baseline in patients and care givers in the intervention group compared with the controls ( differences were 1.5 ( 95 % confidence interval 1.3 to 1.7 ) for the process scale ; -11.7 ( -13.6 to -9.7 ) for the performance scale ; and ( 11.0 ; 9.2 to 12.8 ) for the competence scale ) . This improvement was still significant at three months . The number needed to treat to reach a clinical ly relevant improvement in motor and process skills score was 1.3 ( 1.2 to 1.4 ) at six weeks . Effect sizes were 2.5 , 2.3 , and 1.2 , respectively , at six weeks and 2.7 , 2.4 , and 0.8 , respectively , at 12 weeks . CONCLUSIONS Occupational therapy improved patients ' daily functioning and reduced the burden on the care giver , despite the patients ' limited learning ability . Effects were still present at 12 weeks , which justifies implementation of this intervention . TRIAL REGISTRATION Clinical Trials NCT00295152 [ Clinical Trials.gov ] Spouse-caregivers of Alzheimer 's disease patients were r and omly assigned to either a treatment group ( individual and family counseling , support group participation , and ad hoc consultation ) or a control group ( only routine support ) . In the first year after intake , the treatment group had less than half as many nursing home placements as the control group . This suggests that a comprehensive counseling program can reduce the socioeconomic impact of Alzheimer 's disease . Nursing home placement also was affected by the patient 's need for assistance with activities of daily living , patient income , and the age of the patients and caregivers CONTEXT Optimal treatment to postpone functional decline in patients with dementia is not established . OBJECTIVE To test a nonpharmacologic intervention realigning environmental dem and s with patient capabilities . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve 2-group r and omized trial ( Care of Persons with Dementia in their Environments [ COPE ] ) involving patients with dementia and family caregivers ( community-living dyads ) recruited from March 2006 through June 2008 in Pennsylvania . INTERVENTIONS Up to 12 home or telephone contacts over 4 months by health professionals who assessed patient capabilities and deficits ; obtained blood and urine sample s ; and trained families in home safety , simplifying tasks , and stress reduction . Control group caregivers received 3 telephone calls and educational material s. MAIN OUTCOME MEASURES Functional dependence , quality of life , frequency of agitated behaviors , and engagement for patients and well-being , confidence using activities , and perceived benefits for caregivers at 4 months . RESULTS Of 284 dyads screened , 270 ( 95 % ) were eligible and 237 ( 88 % ) r and omized . Data were collected from 209 dyads ( 88 % ) at 4 months and 173 ( 73 % ) at 9 months . At 4 months , compared with controls , COPE patients had less functional dependence ( adjusted mean difference , 0.24 ; 95 % CI , 0.03 - 0.44 ; P = .02 ; Cohen d = 0.21 ) and less dependence in instrumental activities of daily living ( adjusted mean difference , 0.32 ; 95 % CI , 0.09 - 0.55 ; P = .007 ; Cohen d = 0.43 ) , measured by a 15-item scale modeled after the Functional Independence Measure ; COPE patients also had improved engagement ( adjusted mean difference , 0.12 ; 95 % CI , 0.07 - 0.22 ; P = .03 ; Cohen d = 0.26 ) , measured by a 5-item scale . COPE caregivers improved in their well-being ( adjusted mean difference in Perceived Change Index , 0.22 ; 95 % CI , 0.08 - 0.36 ; P = .002 ; Cohen d = 0.30 ) and confidence using activities ( adjusted mean difference , 0.81 ; 95 % CI , 0.30 - 1.32 ; P = .002 ; Cohen d = 0.54 ) , measured by a 5-item scale . By 4 months , 64 COPE dyads ( 62.7 % ) vs 48 control group dyads ( 44.9 % ) eliminated 1 or more caregiver-identified problems ( chi(2/1 ) = 6.72 , P = . 01 ) . CONCLUSION Among community-living dyads , a nonpharmacologic biobehavioral environmental intervention compared with control result ed in better outcomes for COPE dyads at 4 months . Although no group differences were observed at 9 months for patients , COPE caregivers perceived greater benefits . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00259454 The goal of this study was to evaluate a community-based psychoeducational-nursing intervention design ed to teach home caregivers to manage behavioral problems of persons with Alzheimer 's disease and related dementias ( ADRD ) using the Progressively Lowered Stress Threshold ( PLST ) model , and to compare this intervention with routine information and referrals for case management , community-based services , and support groups . Previous caregiver studies have overwhelmingly pointed to the adverse effects of caregiving on the caregivers ' physical and mental health , and high prevalence rates of depression among caregivers of persons with ADRD have consistently been reported . Therefore , a primary aim was to evaluate the impact of the intervention on caregivers ' affective responses , especially depression . Data from both the Profile of Moods States and the Geriatric Depression Rating Scale support the effectiveness of this intervention in decreasing depression among caregivers who received the experimental training . Additional analysis of factors associated with caregiver depression are also reported . The pivotal role of psychiatric nurses in the assessment and treatment of depression among caregivers of persons with ADRD is discussed Seven caregivers of a home-dwelling spouse with Alzheimer 's disease were trained during 12 weekly home visits to implement behavior management programs including written cuing procedures in response to repetitive verbalizations . Data from 7 trained caregivers and 7 matched control caregivers who only tracked repetitive behavior were compared . Results revealed that trained caregivers were successful at decreasing patient repetitions using written cues . Patients of control subjects showed no systematic changes in behavioral disturbances due to behavior tracking . In addition , intervention effects lasted for 16 weeks or longer and several caregivers reported applying the cuing intervention to other , nontargeted behaviors . Trained caregivers ' perceptions of their efficacy in managing difficult patient behavior improved significantly at the 3-month follow-up assessment when program staff were no longer visiting them weekly Although the literature is replete with studies examining the psychological concomitants and interventions for Alzheimer 's disease ( AD ) family caregivers , a surprisingly small amount of research exists on anxiety . Given prevalence rates suggesting that anxiety significantly impacts one in three family caregivers , brief group cognitive-behavioral therapy ( CBT ) interventions may offer assistance . To assess CBT 's effectiveness , 38 anxious AD family caregivers were recruited and r and omly assigned to a nine-week group CBT intervention or to a waitlist control . Caregivers r and omized to CBT demonstrated less anxiety on self-report and clinician-administered question naires than waitlist group participants at posttreatment and six-week follow-up assessment s. A sub sample of caregivers also demonstrated improved sleep , as assessed through actigraph measurements . Additional study is recommended with diverse anxious family caregiving groups to further investigate the effectiveness of brief CBT group interventions PURPOSE This study examines the short-term impact of two theoretically based psychoeducational small group interventions with distressed caregivers , and it also examines the role of specific moderator and mediator variables on caregiver outcomes . DESIGN AND METHODS Female participants ( N = 169 ) aged 50 and older who were caring for a community-dwelling relative with a dementing illness were r and omly assigned to one of three treatment interventions : anger management , depression management , or a wait-list control group . These interventions took place over a 3- to 4-month period . The primary outcomes examined were anger or hostile mood , depressed mood , frequency of use of positive and negative coping strategies , and perceived caregiving self-efficacy . RESULTS Significant main effects in the expected direction were found for changes in most of these measures . Participants in both anger management and depression management groups had significant reductions in their levels of anger or hostility and depression from Time 1 to Time 2 in comparison to participants in the wait-list control group . Use of positive cognitive coping strategies increased in the anger management group only . Self-efficacy significantly increased for participants in both intervention groups , and it was also demonstrated to function as a mediator of intervention effects . Pretreatment levels of depressive symptoms and anger expression style ( Anger Expression-Out ) moderated the relative effects of the two interventions on mood and coping . IMPLICATION S These data are consistent with a growing body of evidence supporting the effectiveness of skills training , in small groups , to improve both the affective states and the type of coping strategies used by caregivers . In addition , this study underscores the need to evaluate key pretreatment variables in order to determine which form of treatment may be more compatible with caregiver characteristics and thus more likely to be beneficial to individuals 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 PURPOSE We determine the main outcome effects of a 12-month computer-mediated automated interactive voice response ( IVR ) intervention design ed to assist family caregivers managing persons with disruptive behaviors related to Alzheimer 's disease ( AD ) . DESIGN AND METHODS We conducted a r and omized controlled study of 100 caregivers , 51 in the usual care control group and 49 in the technology intervention group , who received yearlong access to an IVR-mediated system . The system provided caregiver stress monitoring and counseling information , personal voice-mail linkage to AD experts , a voice-mail telephone support group , and a distraction call for care recipients . We conducted analyses by using a repeated measures approach for longitudinal data and an intention-to-treat analytic approach . Outcomes included the caregiver 's appraisal of the bothersome nature of caregiving , anxiety , depression , and mastery at baseline , 6 , 12 , and 18 months . RESULTS There was a significant intervention effect as hypothesized for participants with lower mastery at baseline on all three outcomes : bother ( p = .04 ) , anxiety ( p = .01 ) , and depression ( p = .007 ) . Additionally , wives exhibited a significant intervention effect in the reduction of the bothersome nature of caregiving ( p = .02 ) . IMPLICATION S Wives who exhibited low mastery and high anxiety benefited the most from the automated telecare intervention . Findings suggest that , to optimize outcome effects , similar interventions should be tailored to match the users ' characteristics and preferences BACKGROUND The study objective was to determine the health and quality -of-life effects of moderate-intensity exercise among older women family caregivers . METHODS This 12-month r and omized controlled trial involved a volunteer sample of 100 women aged 49 to 82 years who were sedentary , free of cardiovascular disease , and caring for a relative with dementia . Participants were r and omized to 12 months of home-based , telephone-supervised , moderate-intensity exercise training or to an attention-control ( nutrition education ) program . Exercise consisted of four 30- to 40-minute endurance exercise sessions ( brisk walking ) prescribed per week at 60 % to 75 % of heart rate reserve based on peak treadmill exercise heart rate . Main outcomes were stress-induced cardiovascular reactivity levels , rated sleep quality , and reported psychological distress . RESULTS Compared with nutrition participants ( NU ) , exercise participants ( EX ) showed significant improvements in the following : total energy expenditure ( baseline and post-test means [ SD ] for EX = 1.4 [ 1.9 ] and 2.2 [ 2.2 ] kcal/kg/day ; for NU = 1.2 [ 1.7 ] and 1.2 [ 1.6 ] kcal/kg/day ; p < .02 ) ; stress-induced blood pressure reactivity ( baseline and post-test systolic blood pressure reactivity values for EX = 21.6 [ 12.3 ] and 12.4 [ 11.2 ] mm Hg ; for NU = 17.9 [ 10.2 ] and 17.7 [ 13.8 ] mm Hg ; p < .024 ) ; and sleep quality ( p < .05 ) . NU showed significant improvements in percentages of total calories from fats and saturated fats relative to EX ( p values < .01 ) . Both groups reported improvements in psychological distress . Conclusions . Family caregivers can benefit from initiating a regular moderate-intensity exercise program in terms of reductions in stress-induced cardiovascular reactivity and improvements in rated sleep quality PURPOSE The majority of persons with Alzheimer 's disease ( AD ) are cared for at home by a family member such as a spouse or daughter . Caregiving places enormous dem and s on these caregivers , and the negative consequences associated with caregiving are well documented . This paper reports results from the Miami site of the REACH ( Re sources for Enhancing Alzheimer 's Caregiver Health ) program that examined the efficacy of a family therapy and technology-based intervention in reducing depressive symptoms ( according to the Center for Epidemiological Studies Depression scale ) among family caregivers of AD patients at 6 months and 18 months follow-up . DESIGN AND METHODS There were 225 White American and Cuban American caregivers that were r and omized into a structural ecosystems therapy , structural ecosystems therapy + computer-telephone integrated system , or minimal support control condition . RESULTS Caregivers in the combined family therapy and technology intervention experienced a significant reduction in depressive symptoms at 6 months . The 18-month follow-up data indicated that the intervention was particularly beneficial for Cuban American husb and and daughter caregivers . IMPLICATION S The results indicate that information technology has a promising role in alleviating distress and depression among groups of AD caregivers . The data also demonstrate that interventions have differential impacts according to ethnic group and the caregiver-patient relationship 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 OBJECTIVES Family caregiving is an integral part of the care system for persons with dementing disorders , such as Alzheimer 's disease . This study tested role-training intervention as a way to help family caregivers appreciate and assume a more clinical belief set about caregiving and thereby ameliorate the adverse outcomes associated with caregiving . DESIGN Training effectiveness was tested in a trial in which family care receiver dyads were r and omly assigned to training beginning immediately or were placed in a wait-list control group and assigned to receive training in 5 to 6 months , following completion of data collection . SETTING A community-based 14-hour training program provided in seven weekly 2-hour sessions . The training program curriculum was built on a stress and coping theory base . Recruitment and r and omization were ongoing . Programs were begun every 2 months over a two and one half-year period for a total of 16 programs . PARTICIPANTS Community health and social service agencies referred primary caregivers and at least one other family member of community-dwelling persons with dementia to participate . MEASUREMENTS Data reported in this paper were gathered from each participating family at entry to the study and 5 months later . St and ard measures of beliefs about caregiving , burden , depression , and reaction to care receiver behavior were administered to caregivers . A st and ard measure of mental status was administered to the person with dementia and st and ardized instruments were used to gather information from caregivers concerning care receivers ' behavior and abilities to perform activities of daily living ( ADLs ) . RESULTS Data were analyzed from 94 caregiver/care receiver dyads with complete sets of data . Treatment and control caregivers and care receivers were similar at baseline , and care receivers in both groups declined similarly over the 5-month period . Significant within-group improvements occurred with treatment group caregivers on measures of beliefs about caregiving ( P = .044 ) and reaction to behavior ( P = .001 ) . When outcomes were compared , treatment group caregivers were significantly different ( in the expected direction ) from those in the control group on measures of the stress mediator , beliefs ( P = .025 ) , and key outcomes , response to behavior ( P = .019 ) , depression ( P = .040 ) , and burden ( P = .051 ) . There was a significant positive association between the strengthened mediator , the caregivers ' having less-emotionally enmeshed beliefs about caregiving roles and responsibilities , and the outcome , namely improvements in burden ( P = .019 ) and depression ( P = .007 ) . CONCLUSION A caregiver training intervention focused on the work of caregiving and targeted at knowledge , skills , and beliefs benefits caregivers in important outcome dimensions . The results suggest the benefits of providing information , linkage , and role coaching to dementia family caregivers 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 To investigate the effectiveness of a home‐based caregiver training program for caregivers of elders with dementia and behavioral problems |
12,141 | 25,909,234 | Topical diquafosol seems to be a safe therapeutic option for the treatment of dry eye .
However , the topical administration of diquafosol seems to be beneficial in improving the integrity of the epithelial cell layer of the ocular surface and mucin secretion in patients with dry eyes . | PURPOSE To evaluate the efficacy and safety of topical diquafosol ophthalmic solution for treatment of dry eye . | PURPOSE Dry eye syndrome ( DES ) is believed to be one of the most common ocular problems in the United States ( US ) , particularly among older women . However , there are few studies describing the magnitude of the problem in women and how this may vary with demographic characteristics . DESIGN Cross-sectional prevalence survey . METHODS STUDY POPULATION we surveyed 39,876 US women participating in the Women 's Health Study about a history of diagnosed DES and dry eye symptoms . MAIN OUTCOME MEASURE we defined DES as the presence of clinical ly diagnosed DES or severe symptoms ( both dryness and irritation constantly or often ) . We calculated the age-specific prevalence of DES and adjusted the overall prevalence to the age distribution of women in the US population . We used logistic regression to examine associations between DES and other demographic factors . RESULTS The prevalence of DES increased with age , from 5.7 % among women < 50 years old to 9.8 % among women aged > or = 75 years old . The age-adjusted prevalence of DES was 7.8 % , or 3.23 million women aged > or = 50 in the US . Compared with Whites , Hispanic ( odds ratio [ OR ] = 1.81 , confidence interval [ CI ] = 1.18 - 2.80 ) and Asian ( OR = 1.77 , CI = 1.17 - 2.69 ) women were more likely to report severe symptoms , but not clinical ly diagnosed DES . There were no significant differences by income ( P([trend ] ) = .78 ) , but more educated women were less likely to have DES ( P([trend ] ) = .03 ) . Women from the South had the highest prevalence of DES , though the magnitude of geographic differences was modest . CONCLUSIONS Dry eye syndrome leading to a clinical diagnosis or severe symptoms is prevalent , affecting over 3.2 million American women middle-aged and older . Although the condition is more prevalent among older women , it also affects many women in their 40s and 50s . Further research is needed to better underst and DES and its impact on public health and quality of life PURPOSE To examine whether low-dose aspirin ( 325 mg on alternate days ) reduces the risk of age-related cataract and subtypes . This report extends previous findings , including both subtypes and additional newly identified incident cases since the earlier report . METHODS All 20,979 participants in the Physicians ' Health Study , a r and omized trial of aspirin and beta-carotene among U.S. male physicians age 40 - 84 in 1982 , who did not report cataract at baseline were included . Average follow-up was five years . The main outcome measure was incident , age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse , based on self-report confirmed by medical record review . RESULTS 501 age-related cataracts were diagnosed during follow-up , including 416 with nuclear sclerosis and 212 with a posterior subcapsular component ; 318 cataracts progressed to surgical extraction . Overall , there were 245 cataracts in the aspirin group and 256 in the placebo group ( relative risk [ RR ] , 0.94 ; 95 % confidence interval [ CI ] , 0.79 to 1.13 ; P = 0.52 ) . Cataract extraction s were 19 % less frequent in the aspirin than in the placebo group ( RR , 0.81 ; 95 % CI , 0.65 to 1.01 ; P = 0.06 ) . In subgroup analyses of subtypes , aspirin takers had a lower risk of posterior subcapsular cataract ( RR , 0.74 ; 95 % CI , 0.57 to 0.98 ; P = 0.03 ) but not nuclear sclerosis ( RR , 0.96 ; 95 % CI , 0.79 to 1.16 ; P = 0.65 ) cataract . CONCLUSIONS Overall , these r and omized trial data tend to exclude a large benefit of five years of low-dose aspirin therapy on cataract development and extraction . The data are compatible with a modest benefit on cataract extraction for this duration of aspirin therapy . Subgroup analyses raise the possibility of a modest , but potentially important , protective effect of aspirin on posterior subcapsular cataract , a particularly disabling subtype Purpose To assess the additive effect of diquafosol tetrasodium on sodium hyaluronate monotherapy in patients with dry eye syndrome . Methods This study evaluated 64 eyes of 32 patients ( age : 62.6±12.8 years ( mean±SD ) ) in whom treatment with 0.1 % sodium hyaluronate was insufficiently responsive . The eyes were r and omly assigned to one of the two regimens in each patient : topical administration of sodium hyaluronate and diquafosol tetrasodium in one eye , and that of sodium hyaluronate in the other . Before treatment , and 2 and 4 weeks after treatment , we determined tear volume , tear film break-up time ( BUT ) , fluorescein and rose bengal vital staining scores , subjective symptoms , and adverse events . Results We found a significant improvement in BUT ( P=0.049 , Dunnett test ) , fluorescein and rose bengal staining scores ( P=0.02 ) , and in subjective symptoms ( P=0.004 for dry eye sensation , P=0.02 for pain , and P=0.02 for foreign body sensation ) 4 weeks after treatment in the diquafosol eyes . On the other h and , we found no significant change in these parameters after treatment in the control eyes . Conclusions In dry eyes , where sodium hyaluronate monotherapy was insufficient , diquafosol tetrasodium was effective in improving objective and subjective symptoms , suggesting its viability as an option for the additive treatment of such eyes Purpose : The aim of this study was to evaluate the treatment effect of diquafosol 3 % with preservative-free sodium hyaluronate 0.1 % eye drops in dry eye syndrome . Methods : In total , 150 patients with dry eye syndrome were divided r and omly into 3 groups . Group 1 ( 50 patients ) was treated 4 times daily with preserved sodium hyaluronate 0.1 % , group 2 ( 50 patients ) was treated 4 times daily with diquafosol 3 % , and group 3 ( 50 patients ) was treated 4 times daily with diquafosol 3 % and preservative-free sodium hyaluronate 0.1 % eye drops for 3 months . Ocular surface disease index ( OSDI ) score , tear film break-up time , Schirmer I test , corneal fluorescein staining , and impression cytology were evaluated . Results : There were significant improvements in the OSDI score , tear film break-up time , Schirmer I score , fluorescein and Rose Bengal staining , goblet cell density , and impression cytological findings in groups 2 and 3 compared with those for group 1 in patients with dry eye syndrome at 1 , 2 , and 3 months ( P < 0.05 ) . There were statistically significant improvements in the OSDI score ( −8.48 ± 0.97 , −5.69 ± 0.78 ; P = 0.02 ) , fluorescein ( −1.43 ± 0.21 , −1.02 ± 0.18 ; P = 0.03 ) , and Rose Bengal staining ( −1.12 ± 0.26 , −0.75 ± 0.12 ; P = 0.03 ) , goblet cell density ( 89.65 ± 14.39 , 70.36 ± 16.75 ; P = 0.03 ) , and impression cytological findings ( −0.53 ± 0.12 , −0.34 ± 0.90 ; P = 0.01 ) in group 3 compared with those in group 2 at 3 months . Conclusions : Treatment with diquafosol 3 % with preservative-free sodium hyaluronate 0.1 % was more effective than diquafosol 3 % monotherapy or treatment with preserved sodium hyaluronate 0.1 % in dry eye syndrome . Preservative-free sodium hyaluronate 0.1 % eye drops can increase the effect of diquafosol 3 % in dry eye syndrome Activation of P2Y2 receptors in various tissues results in secretion of ions , fluid and mucin . In situ hybridization experiments on fresh primate tissue confirm the presence of mRNA coding for the gene expression of the P2Y2 receptor in the conjunctiva and the meibomian gl and . Topical ocular administration of nucleotides causes increased chloride and mucin secretion , as well as fluid transport . These pharmacologic findings lead to the hypothesis that P2Y2 receptor agonists may have therapeutic efficacy in diseases of impaired ocular hydration Purpose : To investigate the effects of diquafosol sodium ( DQS ) eye drops , a purinergic P2Y2 receptor agonist , on tear film stability in patients with unstable tear film ( UTF ) . Methods : Two prospect i ve studies were conducted . One was an exploratory nonr and omized trial on 39 eyes with dry eye symptoms and short tear film break-up time ( BUT ) , but without epithelial damage . Changes in symptoms , BUT , Schirmer value , and ocular surface fluorescein staining ( FS ) scores were studied for 3 months . The other was a r and omized clinical trial of DQS and artificial tears ( AT ) in 17 eyes with short BUT . Eyes with decreased Schirmer values ( ⩽5 mm ) were excluded . Changes in symptoms , BUT , FS scores , and tear film stability using continuous corneal topographic analysis were studied for 4 weeks . Results : In the exploratory study , while Schirmer values were not significantly increased , significant improvements in symptoms and BUT were noted at both 1 and 3 months . In the r and omized clinical trial , significant improvements in symptoms were noted in the DQS group , but not in the AT group , at 2 weeks . BUT was significantly prolonged in the DQS group at 4 weeks but not in the AT group . No significant changes were noted in FS scores or tear film stability . Conclusions : DQS improved subjective symptoms and prolonged BUT in eyes with UTF not associated with low tear secretion and ocular surface epithelial damage . Because many patients who have UTF are refractory to conventional treatments , DQS may offer benefits in the treatment of dry eyes |
12,142 | 27,820,416 | The authors of this review recommend full consideration be given to the sample size and study setting prior to implementation of the review recommendations in order to determine applicability to varied clinical setting s. The results section highlights sample size issues for each included study .With this limited evidence , no single intervention was identified that offers a dramatic effect in terms of treating pain and or trauma in breast-feeding women .
However , there is potential for some benefits for reducing pain and increasing comfort and thereby maximising breast-feeding duration .
CONCLUSIONS In terms of prevention , warm water compresses are recommended for the prevention of nipple pain , and simply keeping the nipples clean and dry is recommended for the prevention of cracked nipples .
In terms of treatment , warm water compresses are recommended for the reduction of nipple pain , and expressed breast-milk reduces the duration of cracked nipples .
Hydrogel dressings were associated with a high incidence of infections and their use can not be recommended . | OBJECTIVE The objective of this systematic review was to present the best available evidence related to the management of nipple pain , post childbirth in breast-feeding women .
The specific objective of the review was to determine the effectiveness of interventions used by and for breast-feeding women to prevent and /or reduce nipple pain and trauma .
RESULTS There is a plethora of research that evaluates the effectiveness of the many interventions used to prevent or treat nipple pain and or trauma for breast-feeding women . | BACKGROUND Sore nipples in breast-feeding mothers are a common cause of premature weaning , and are difficult to treat owing to recurrent trauma and exposure to the infant 's oral flora . OBJECTIVE To compare the safety and efficacy of a hydrogel moist wound dressing ( Elasto-gel , Southwest Technologies Inc , Baltimore , Md ) with the use of breast shells and lanolin cream in the treatment of maternal sore nipples associated with breast-feeding . DESIGN R and omized controlled trial comparing the above treatments for sore nipples . Patients were seen for a maximum of 3 follow-up visits within 10 days , or until the resolution of symptoms . SETTING The Maternal-Infant Lactation Center at the Mercy Hospital of Pittsburgh , Pittsburgh , Pa , a tertiary care teaching hospital in inner-city Pittsburgh . PATIENTS A referred sample of 42 breast-feeding women who presented to the Maternal-Infant Lactation Center for the treatment of sore nipples . All patients with breast infection or chronic unrelated pain conditions were excluded from the study . INTERVENTION After informed consent , patients were r and omized to receive either a hydrogel wound dressing or breast shells and lanolin . All patients underwent a history , physical examination of the infant and the mother 's breasts , assessment of breast-feeding technique , and breast-feeding instruction . MAIN OUTCOME MEASURES The degree of pain on self-report question naires and the change in scores for physical examination , breast-feeding technique , and pain behaviors during breast-feeding . RESULTS Although both treatments , in association with instruction in breast-feeding technique , were effective , greater improvement was seen in the group using breast shells and lanolin . This reached statistical significance for physician-rated healing ( P<.01 ) and self-reported pain ( P<.05 ) . There were significantly more infections in the dressing group ( P<.05 ) , which result ed in early discontinuation of the study . CONCLUSIONS Prevention of sore nipples by teaching proper technique on the initiation of breast-feeding should be instituted . For those cases in which sore nipples do develop , breast shells and lanolin in association with instruction in breast-feeding technique are more effective than moist wound dressings . Lanolin and shells should remain first-line therapy BACKGROUND Nipple soreness is one reason why breastfeeding women wean their infants . This study examined the effectiveness of three topical agents -- USP-modified lanolin , warm water compresses , and expressed breast milk with air drying -- in alleviating nipple pain , and if early predictors of breastfeeding at six weeks could be determined . METHODS One hundred seventy-seven breastfeeding , primiparous women were r and omly assigned to one of four groups . All women received education about breastfeeding technique . Numeric rating scales were used to discriminate levels of pain intensity , pain affect , and strength of sucking on day 1 . Participants were interviewed by telephone on postpartum days 4 , 7 , and 14 , and during week 6 using the same scales . RESULTS No significant differences were found among groups for pain intensity , pain affect , or duration of breastfeeding . Results of a logistic regression indicated that older mothers and those who were exclusively breastfeeding ( no supplemental feeding ) were most likely to be breastfeeding six weeks postpartum . Raw scores supported the use of warm compresses . CONCLUSION Further investigation is required into ways of supporting young mothers and how caregivers provide support to breastfeeding mothers in the early weeks after childbirth OBJECTIVE To evaluate effectiveness of water versus tea bag compresses in treatment of sore nipples during breastfeeding . DESIGN Prospect i ve , r and omized trial . SETTING Mother-infant care wards in a tertiary care teaching hospital . PARTICIPANTS Sixty-five primiparae with sore nipples who were breastfeeding after a vaginal delivery at 37 or more weeks gestation , who were 36 hours or less postpartum , and had combined mother-infant care . INTERVENTIONS Participants were assigned r and omly to one of six treatment groups with one of three regimens ( tea bag compress , water compress , or no compress ) r and omly assigned to right or left sides . Participants applied the treatments at least four times a day , from Days 1 to 5 postpartum . MAIN OUTCOME MEASURE Reduction of nipple pain . RESULTS Tea bag and water compresses were more effective than no treatment , with no statistically significant difference between the two types of compresses . CONCLUSION Warm water or tea bag compresses are an inexpensive , equally effective treatment for sore nipples during the early postpartum period OBJECTIVE To examine various comfort measures and evaluate their effects in alleviating nipple soreness . DESIGN Prospect ively r and omized , experimental study . SETTING Postpartum unit of a community teaching hospital . PATIENTS Seventy-three primiparous , postpartum , breastfeeding women . INTERVENTIONS Subjects were r and omly assigned to four groups , with all women receiving instruction about breastfeeding and using one of the following treatments : warm moist tea bag compress , warm water compress , expressed milk massaged into the nipple and areola and air dried , instruction only ( control group ) . The subjects completed a question naire each morning for 7 days regarding nipple soreness . MAIN OUTCOME MEASURE Effect of treatments on postpartum nipple pain . RESULTS Subjects in the warm water compress group demonstrated significantly less pain on Day 3 than did the tea or breast milk group . CONCLUSIONS Anticipatory guidance by obstetric nurses may assist breastfeeding women in treating their pain nonpharmacologically This study was design ed to evaluate whether maintenance of a moist environment on the nipple skin during the first week of breast-feeding would improve damaged nipple skin condition , as indicated by the presence of eschar , erythema , and fissures , and reduce pain . Fifty White women applied a polyethylene film dressing with a perimeter adhesive system to a r and omly determined nipple . The dressing was present at all times except during feeding . Subjects were assessed every 48 hours ( four times ) over 7 days . Serial photographic slides were obtained and assessed for skin characteristics . Nipple pain was self-rated with a verbal descriptor scale . Use of an occlusive film dressing on nipple skin during the first week of breast-feeding appeared to have limited influence on improvement in damaged skin condition . Summary scores indicated significant reduction in the amount of eschar on the surface of the nipple . There were no differences in erythema intensity or fissure severity . Use of a dressing significantly reduced nipple pain during the study period Sore and cracked nipples are common and may represent an obstacle to successful breastfeeding . In Italy , it is customary for health professionals to prescribe some type of ointment to prevent or treat sore and cracked nipples . The efficacy of these ointments is insufficiently documented . The incidence of sore and cracked nipples was compared between mothers given routine nipple care , including an ointment ( control group ) , and mothers instructed to avoid the use of nipple creams and other products ( intervention group ) . Breastfeeding duration was also compared between the two groups . Eligible mothers were r and omly assigned , after informed consent , to one of the two groups . No difference was found between the control ( n=96 ) and the intervention group ( n=123 ) in the incidence of sore and cracked nipples and in breastfeeding duration . However , several factors were associated with sore nipples and with breastfeeding duration . The use of a pacifier and of a feeding bottle in the hospital were both associated with sore nipples at discharge ( p=0.02 and p=0.03 , respectively ) . Full breastfeeding up to 4 months postpartum was significantly associated with the following early practice s : breastfeeding on dem and , rooming-in at least 20 hours/day , non-use of formula and pacifier , no test-weighing at each breastfeed . The incidence of sore and cracked nipples and the duration of breastfeeding were not influenced by the use of a nipple ointment . Other interventions , such as providing the mother with guidance and support on positioning and latching , and modifications of hospital practice s may be more effective in reducing nipple problems OBJECTIVE To assess whether an antenatal teaching session on position and attachment of the baby on the breast had an effect on postnatal nipple pain , nipple trauma and breast feeding duration . The study was planned as a pilot study to allow an adequate sample size to be calculated for a larger study . DESIGN An observer blind experimental design was used . Women were r and omly assigned to either the experimental group teaching session or the control group . SETTING One public hospital in Western Australia . PARTICIPANTS 70 primiparae who intended to breast feed their baby were recruited from the antenatal clinic of the study hospital at 36 weeks ' gestation . INTERVENTION Antenatal group sessions on position and attachment of the baby on the breast were conducted by a lactation consultant . MEASUREMENTS AND FINDINGS During the first four postnatal days , position and attachment was measured by LATCH ( Latch on , Audible swallow , Type of nipple , Comfort and Help ) ( Jensen et al 1994 ) , nipple pain was measured by the Visual Analogue Scale ( VAS ) and nipple trauma was measured by the Nipple Trauma Index ( NTI ) . The analysis of variance ( ANOVA ) results indicated that the women in the experimental group were better able to attach the baby on the breast and had significantly less nipple pain and trauma than the control group . At six weeks postnatally , 31 of the 35 women in the experimental group were breast feeding compared to 10 of the 35 in the control group . CONCLUSIONS AND IMPLICATION S These initial findings suggest that midwives can make the best use of decreasing re sources by using practical ' h and s on ' antenatal group teaching as an effective strategy to increase breast feeding rates BACKGROUND Although lactation experts suggest that a correct positioning and attachment technique reduces breastfeeding problems and enhances long-term breastfeeding , evidence from r and omized trials is lacking . The objective of this study was to evaluate the effect of postpartum positioning and attachment education on breastfeeding outcomes in first-time mothers . METHOD A r and omized trial was performed in a public hospital in Adelaide , South Australia , where 160 first-time mothers were r and omly allocated to receive either structured one-to-one education ( experimental group ) or usual postpartum care ( control group ) within 24 hours of birth . The primary outcome was breastfeeding at 6 weeks and 3 and 6 months postpartum ; other outcomes were nipple pain and trauma in hospital and at 6 weeks and 3 and 6 months , and satisfaction with breastfeeding . RESULTS No significant differences occurred in breastfeeding rates between the groups at each endpoint , although a trend in the direction of lower rates was seen at each endpoint in the experimental group . This group reported less nipple pain on days 2 ( p = 0.004 ) and 3 ( p = 0.04 ) , but this was not sustained on follow-up . No differences were observed in nipple trauma in hospital or in self-reported nipple pain and /or trauma at the three endpoints . Experimental group women were less satisfied with breastfeeding at 3 and 6 months postpartum when using a one-item measure ; however , a multiple-item measure showed no significant differences at the three endpoints . CONCLUSIONS The intervention did not increase breastfeeding duration at any assessment time or demonstrate any differences between the groups on secondary outcomes . The trend toward lower breastfeeding rates in the experimental group suggests a need for a larger trial to evaluate whether or nor postpartum positioning and attachment education may negatively affect breastfeeding |
12,143 | 16,537,739 | This systematic review indicates that endogenous sex hormones may differentially modulate glycemic status and risk of type 2 diabetes in men and women .
High testosterone levels are associated with higher risk of type 2 diabetes in women but with lower risk in men ; the inverse association of SHBG with risk was stronger in women than in men | CONTEXT Inconsistent data suggest that endogenous sex hormones may have a role in sex-dependent etiologies of type 2 diabetes , such that hyper and rogenism may increase risk in women while decreasing risk in men .
OBJECTIVE To systematic ally assess studies evaluating the association of plasma levels of testosterone , sex hormone-binding globulin ( SHBG ) , and estradiol with risk of type 2 diabetes . | Testosterone has immune-modulating properties , and current in vitro evidence suggests that testosterone may suppress the expression of the proinflammatory cytokines TNFalpha , IL-1beta , and IL-6 and potentiate the expression of the antiinflammatory cytokine IL-10 . We report a r and omized , single-blind , placebo-controlled , crossover study of testosterone replacement ( Sustanon 100 ) vs. placebo in 27 men ( age , 62 + /- 9 yr ) with symptomatic and rogen deficiency ( total testosterone , 4.4 + /- 1.2 nmol/liter ; bioavailable testosterone , 2.4 + /- 1.1 nmol/liter ) . Compared with placebo , testosterone induced reductions in TNFalpha ( -3.1 + /- 8.3 vs. 1.3 + /- 5.2 pg/ml ; P = 0.01 ) and IL-1beta ( -0.14 + /- 0.32 vs. 0.18 + /- 0.55 pg/ml ; P = 0.08 ) and an increase in IL-10 ( 0.33 + /- 1.8 vs. -1.1 + /- 3.0 pg/ml ; P = 0.01 ) ; the reductions of TNFalpha and IL-1beta were positively correlated ( r(S ) = 0.588 ; P = 0.003 ) . In addition , a significant reduction in total cholesterol was recorded with testosterone therapy ( -0.25 + /- 0.4 vs. -0.004 + /- 0.4 mmol/liter ; P = 0.04 ) . In conclusion , testosterone replacement shifts the cytokine balance to a state of reduced inflammation and lowers total cholesterol . Twenty of these men had established coronary disease , and because total cholesterol is a cardiovascular risk factor , and proinflammatory cytokines mediate the development and complications associated with atheromatous plaque , these properties may have particular relevance in men with overt vascular disease We conducted a prospect i ve , nested , case-control study of inflammatory markers as predictors of type 2 diabetes among 32,826 women who provided blood sample s in 1989 through 1990 in the Nurses ' Health Study . Among women free of diabetes , cardiovascular disease , or cancer at baseline , 737 had developed diabetes by 2000 . Control women ( n = 785 ) were selected matched on age , fasting status , race , and BMI for cases in the top BMI decile . Baseline levels of tumor necrosis factor (TNF)-alpha receptor 2 , interleukin (IL)-6 , and C-reactive protein ( CRP ) were significantly higher among case than control subjects ( all P < /= 0.001 ) . After adjusting for BMI and other lifestyle factors , all three biomarkers significantly predicted diabetes risk ; the odds ratios ( ORs ) comparing extreme quintiles were 1.64 ( 95 % CI 1.10 - 2.45 ) for TNF-alphaR2 , 1.91 ( 1.27 - 2.86 ) for IL-6 , and 4.36 ( 2.80 - 6.80 ) for CRP ( P for trend < 0.001 for all biomarkers ) . In a multivariate model simultaneously including the three biomarkers , only CRP levels were significantly associated with risk of diabetes ( OR comparing extreme quintiles of CRP = 3.99 , P for trend < 0.001 ) . These data support the role of inflammation in the pathogenesis of type 2 diabetes . Elevated CRP levels are a strong independent predictor of type 2 diabetes and may mediate associations of TNF-alphaR2 and IL-6 with type 2 diabetes Serum and rogen levels decline with aging in normal males , such that a significant number of men over 60 yr of age will have a mean serum total testosterone ( T ) level near the low end of the normal adult range . It is not known whether lower T levels in older men have an effect on and rogen-responsive organ systems , such as muscle , bone , bone marrow , and prostate , nor are there data to evaluate the relative benefits and risks of T supplementation in older men . We assessed the physiological and biochemical effects of T therapy in 13 healthy men , 57 - 76 yr old , who had low or borderline low serum T levels ( < or = 13.9 nmol/L ) . Intramuscular testosterone enanthate ( TE ; 100 mg weekly ) and placebo injections were given for 3 months each . Before treatment and at the end of both 3-month treatment regimens , lean body mass , body fat , biochemical parameters of bone turnover , hematological parameters , lipoprotein profiles , and prostate parameters [ such as prostate-specific antigen ( PSA ) ] were evaluated . Serum T levels rose in all subjects with TE treatment , such that the lowest level of T during a week 's period was 19.7 + /- 0.7 nmol/L ( mean + /- SE ) . After 3 months of TE treatment , lean body mass was significantly increased , and urinary hydroxyproline excretion was significantly depressed . With TE treatment , there was a significant increase in hematocrit , a decline in total cholesterol and low density lipoprotein cholesterol , and a sustained increase in serum PSA levels . Placebo treatment led to no significant changes in any of these parameters . We conclude that short term ( 3 months ) TE supplementation to healthy older men who have serum T levels near or below the lower limit of normal for young adult men results in an increase in lean body mass and possibly a decline in bone resorption , as assessed by urinary hydroxyproline excretion , with some effect on serum lipoproteins , hematological parameters , and PSA . The sustained stimulation of PSA and the increase in hematocrit that occur with physiological TE supplementation suggest that older men should be screened carefully and followed periodically throughout T therapy We recently described a connection between and rogens and ghrelin in women affected by the polycystic ovary syndrome . To further investigate the interaction between sex steroids and ghrelin , we investigated circulating ghrelin levels in a group of hypogonadal men before and after therapeutic intervention aim ing at normalization low testosterone ( T ) concentrations . Seven hypogonadal men were compared with nine overweight/moderately obese men matched for body mass index and body fat distribution parameters , as well as with 10 normal weight controls . Total and free T and plasma ghrelin levels were significantly lower in the hypogonadal men than in the control groups . Hypogonadal men also had a significantly higher insulin resistance state . Ghrelin levels were positively correlated with both total and free T concentrations . A significant correlation was also found between ghrelin and the anthropometric parameters and the insulin resistance indexes . However , in a multiple regression analysis in which a correction for all covariants was performed , only the relationship with total and free T persisted . After the 6-month replacement T therapy , ghrelin levels of hypogonadal patients increased and did not differ significantly in comparison with both control groups . The positive correlation between ghrelin and and rogens still persisted after T replacement therapy , after adjusting for confounding variables . These data further indicate that sex hormones modulate circulating ghrelin concentrations in humans . This may be consistent with the concept that ghrelin may exert a relevant role in the endocrine network connecting the control of the reproductive system with the regulation of energy balance We evaluated the association of hemostatic factors with insulin resistance in relation to reproductive hormones including FSH , estradiol , testosterone , and SHBG . SHBG was used to calculate the free estradiol index and free and rogen index . We studied 3,200 women , aged 42 - 52 yr , in the Study of Women 's Health Across the Nation , a prospect i ve multiethnic study of the menopausal transition . We measured the hemostatic factors , fibrinogen , factor VIIc , tissue plasminogen activator ( t-PA ) , and plasminogen activator inhibitor type 1 ( PAI-1 ) , as well as glucose and insulin to calculate insulin resistance . After adjustment for body mass index , site , and ethnicity , SHBG was correlated with PAI-1 ( partial r = -0.30 ) and t-PA ( partial r = -0.12 ) . Although testosterone was associated with t-PA ( partial r = 0.13 ) and PAI-1 ( partial r = 0.07 ) , free and rogen index was strongly correlated with t-PA ( partial r = 0.18 ) and PAI-1 ( partial r = 0.26 ) . SHBG modified the association of hemostatic factors with insulin resistance . Women with greater insulin resistance had lower SHBG and higher PAI-1 . Estrogen measures were not associated with insulin resistance . The influence of sex hormones on hemostatic factors and insulin resistance is poorly understood . SHBG , which influences the amount of bioavailable hormone , significantly modified the association of PAI-1 and t-PA with insulin resistance . The longitudinal Study of Women 's Health Across the Nation will help us discern whether this interaction contributes to heart disease and diabetes among postmenopausal women CONTEXT GnRH agonists markedly increase fat mass in men with prostate cancer , but little is known about the effects of treatment on insulin sensitivity . OBJECTIVE The objective of the study was to assess the effects of short-term GnRH agonist treatment on insulin sensitivity . DESIGN This was a prospect i ve 12-wk study . SETTING The study was conducted at a general clinical research center . PATIENTS OR OTHER PARTICIPANTS We studied 25 men with locally advanced or recurrent prostate cancer , no radiographic evidence of metastases , no history of diabetes mellitus , and no evidence of diabetes mellitus at baseline visit . INTERVENTION Leuprolide depot and bicalutamide were used in the study . MAIN OUTCOME MEASURES Oral glucose tolerance tests and body composition assessment by dual-energy x-ray absorptiometry were performed at baseline and wk 12 . The primary study outcome was change in insulin sensitivity index . RESULTS Mean ( + /- se ) percentage fat body mass increased by 4.3 + /- 1.3 % from baseline to wk 12 ( P = 0.002 ) . Insulin sensitivity index decreased by 12.9 + /- 7.6 % ( P = 0.02 ) . Insulin sensitivity by homeostatic model assessment decreased by 12.8 + /- 5.9 % ( P = 0.02 ) . Fasting plasma insulin levels increased by 25.9 + /- 9.3 % ( P = 0.04 ) . Mean glycosylated hemoglobin also increased significantly ( P < 0.001 ) . CONCLUSIONS Short-term treatment with leuprolide and bicalutamide significantly increased fat mass and decreased insulin sensitivity in men with prostate cancer . These observations suggest that GnRH agonists may increase the risk of diabetes mellitus and cardiovascular disease in older men Mathematical methods exist to determine the fractions of sex hormones bound to albumin , bound to sex hormone binding globulin ( SHBG ) , or unbound , using total hormone concentration and SHBG concentration . We used data from eight prospect i ve studies of postmenopausal women to assess the validity of these estimates for fractions of estradiol ( E2 ) and to investigate the impact of using calculated values in breast cancer relative risk ( RR ) models . Comparisons were made between measured and calculated concentrations of free and non-SHBG-bound E2 in four studies . Relationships between the hormone fractions were investigated and a sensitivity analysis of the calculation performed . Breast cancer RRs were estimated using conditional logistic regression by quintiles of free E2 . There is a high correlation ( r > 0.91 ) between calculated and measured values of both free and non-SHBG-bound E2 . The calculation is highly sensitive to total hormone concentration but is relatively insensitive to SHBG concentration . In studies with both measured and calculated values , the RRs of breast cancer by quintile of free E2 were almost identical for both estimates ; using calculated values in all possible studies the RR in the highest compared with the lowest quintile of free E2 was 2.29 ( 95 % confidence interval , 1.65 - 3.19 ) . The mathematical method used to calculate fractions of E2 is valid , and RR analyses using calculated values produce similar results to those using measured values . This suggests that for epidemiological studies , it is only necessary to measure total E2 concentration and SHBG concentration , with hormone fractions being obtained by calculation , producing savings in cost , time , and serum The objective of this study was to assess the effects of oral testosterone supplementation therapy on glucose homeostasis , obesity and sexual function in middle-aged men with type 2 diabetes and mild and rogen deficiency . Forty-eight middle-aged men , with type 2 diabetes , ( visceral ) obesity and symptoms of and rogen deficiency , were included in this open-label study . Twenty-four subjects received testosterone undecanoate ( TU ; 120 mg daily , for 3 months ) ; 24 subjects received no treatment . Body composition was analyzed by bio-impedance . Parameters of metabolic control were determined . Symptoms of and rogen deficiency and erectile dysfunction were scored by self-administered question naires . TU had a positive effect on ( visceral ) obesity : statistically significant reduction in body weight ( 2.66 % ) , waist-hip ratio ( -3.96 % ) and body fat ( -5.65 % ) ; negligible changes were found in the control group . TU significantly improved metabolic control : decrease in blood glucose values and mean glycated hemoglobin ( HbA1c ) ( from 10.4 to 8.6 % ) . TU treatment significantly improved symptoms of and rogen deficiency ( including erectile dysfunction ) , with virtually no change in the control group . There were no adverse effects on blood pressure or hematological , biochemical and lipid parameters , and no adverse events . Oral TU treatment of type 2 diabetic men with and rogen deficiency improves glucose homeostasis and body composition ( decrease in visceral obesity ) , and improves symptoms of and rogen deficiency ( including erectile dysfunction ) . In these men , the benefit of testosterone supplementation therapy exceeds the correction of symptoms of and rogen deficiency and also includes glucose homeostasis and metabolic control OBJECTIVE The objective was to examine prospect ively the association between low testosterone and sex hormone-binding globulin ( SHBG ) levels and the subsequent development of type 2 diabetes in men . RESEARCH DESIGN AND METHODS Analyses were conducted on the cohort of the Massachusetts Male Aging Study , a population -based r and om sample of men aged 40 - 70 . Of the 1,709 men enrolled in 1987 - 1989 ( T1 ) , 1,156 were followed up 7 - 10 years later ( T2 ) . Testosterone and SHBG levels at T1 were used to predict new cases of diabetes between T1 and T2 . RESULTS After controlling for potential confounders , diabetes at follow-up was predicted jointly and independently by lower baseline levels of free testosterone and SHBG . The odds ratio for future diabetes was 1.58 for a decrease of 1SD in free testosterone ( 4 ng/dl ) and 1.89 for a 1SD decrease in SHBG ( 16 nmol/l ) , both significant at P < 0.02 . CONCLUSIONS Our prospect i ve findings are consistent with previous , mainly cross-sectional reports , suggesting that low levels of testosterone and SHBG play some role in the development of insulin resistance and subsequent type 2 diabetes In a previous study we were the first to describe a negative correlation between circulating ghrelin concentrations and and rogen levels in human plasma , suggesting an interaction between ghrelin and the endocrine regulation of reproductive physiology . We now investigated a potential direct regulatory influence of circulating and rogens on plasma ghrelin levels . Fourteen obese women with polycystic ovary syndrome ( PCOS ) on a hypocaloric diet were r and omly assigned to treatment groups ( open-labeled design ) , receiving either placebo ( no.= 7 ) or the anti and rogen flutamide ( no.=7 ) for 6 months . Anthropometry , visceral ( VAT ) and subcutaneous ( SAT ) adipose tissue ( quantified by computerized tomography ) , plasma hormone levels , insulin sensitivity indexes ( Quantitative Insulin-Sensitivity Check Index-QUICKI ) and Homeostatic Model Assessment applied to the oral glucose tolerance test ( HOMAOGTT ) were evaluated at baseline and at the end of the study . Body weight decreased and insulin resistance indexes improved in both groups . A tendency toward a greater loss of VAT was observed in the flutamide group . Only in the flutamide group was a significant reduction of and rogens levels observed . Plasma ghrelin levels significantly increased following treatment with flutamide , while ghrelin remained unchanged in the placebo group . We observed a negative correlation between changes of ghrelin levels and changes of and rogen plasma concentration in the flutamide-treated group . In the same group a positive correlation was found between plasma ghrelin changes and insulin sensitivity as expressed by HOMAOGTT . Analysis in a multiple regression model , however , showed that plasma ghrelin changes were mainly due to changes of and rogen levels rather than improved insulin sensitivity . We , therefore , conclude that and rogens are independent modulators of circulating ghrelin concentrations The route of estrogen replacement therapy has a major impact on the growth hormone (GH)/insulin-like growth factor-I ( IGF-I ) axis . Estrogen administration by the oral , but not the transdermal route , reduces IGF-I and increases GH levels in postmenopausal women . To investigate whether these perturbations have metabolic consequences , we compared the effects of 24 wk each of oral ( Premarin 1.25 mg ) and transdermal ( Estraderm 100TTS ) estrogen on energy metabolism and body composition in 18 postmenopausal women in an open-label r and omized crossover study . Energy expenditure , lipid oxidation ( lipid(ox ) ) , and carbohydrate oxidation ( CHOox ) were measured by indirect calorimetry in the fasted and fed state before and after 2 and 6 mon treatment . Lean body mass , fat mass , and total body bone mineral density were measured by dual X-ray absorptiometry before and after 6 mon treatment . Mean ( + /-SE ) Luteinizing hormone levels fell to comparable levels during oral and transdermal estrogen , and bone mineral density was significantly increased by both treatments . Mean IGF-I was significantly lower during oral estrogen ( 77+/-7 versus 97+/-7 microg/liter , P < 0.05 ) treatment . Lipid(ox ) 30 - 60 min after a st and ardized meal was significantly lower ( 36+/-5 versus 54+/-5 mg/min , P < 0.01 ) and CHOox higher ( 147+/-13 versus 109+/-12 mg/min , P < 0.05 ) with oral compared with transdermal estrogen . Oral estrogen result ed in a 1.2+/-0.5 kg ( P < 0.05 ) increase in fat mass and a 1.2+/-0.4 kg ( P < 0.01 ) decrease in lean mass compared with transdermal estrogen . Lean body mass ( 0.4+/-0.2 kg ) and fat mass ( 0 . 1+/-0.4 kg ) did not change significantly during transdermal estrogen . In summary , when compared with the transdermal route , oral estrogen reduces lipid(ox ) , increases fat mass , and reduces lean body mass . The route of estrogen therapy confers distinct and divergent effects on substrate oxidation and body composition . The suppression of lipidox during oral estrogen therapy may increase fat mass although the fall in IGF-I may lead to a loss of lean body mass . The route-dependent changes in body composition observed during estrogen replacement therapy may have important implication s for postmenopausal health Most studies of sex hormones and insulin resistance ( IR ) have focused on and rogens ; few have examined the association of endogenous estrogens and IR . We determined the cross-sectional association of endogenous levels of total and bioavailable testosterone and estradiol and SHBG with IR among 845 healthy , postmenopausal women aged 45 - 65 yr . Women were within 10 yr of menopause and not using hormone replacement therapy . Total adiposity was estimated by body mass index , visceral adiposity by waist to hip ratio ( WHR ) , and IR by the homeostasis model assessment . We defined homeostasis model assessment -IR as the highest quartile ( cutpoint , 2.1 ) of the distribution in this cohort . In logistic regression analyses , the odds for IR were significant and increased in a dose-response fashion across each quartile of total estradiol , bioavailable estradiol , and bioavailable testosterone ( all P < 0.001 for linear trend ) . These associations remained significant after adjusting for WHR ; adjusted odds ratios were 4.0 , 6.1 , and 2.7 for total estradiol , bioavailable estradiol , and bioavailable testosterone , respectively , comparing the highest to the lowest quartile ( all P < 0.001 ) . Adjusting for body mass index and WHR together eliminated the linear association of IR with total estradiol and bioavailable testosterone , but the association with bioavailable estradiol remained ( adjusted odds ratio , 2.7 ; P < 0.001 , comparing the highest to the lowest quartile ) . IR was not associated with total testosterone before or after adjusting for adiposity . Lower SHBG levels were associated with higher odds of IR , independent of adiposity . These results suggest that estrogen may be equally or more important than testosterone in the pathway to IR in healthy , young postmenopausal women , with differences not entirely explained by body size Central adiposity , sometimes described as male pattern fat distribution , is adversely related to cardiovascular risk and mortality independent of other measures of obesity . In a cohort of 511 men aged 30 to 79 years in 1972 to 1974 , levels of and rostenedione , testosterone , and sex hormone-binding globulin measured at baseline were inversely related to subsequent central adiposity , estimated 12 years later using the waist-hip circumference ratio . The observed differences in waist-hip ratio between top and bottom tertiles of these hormones and sex hormone-binding globulin were similar to mean waist-hip ratio differences between men with stroke or ischemic heart disease and those without in another prospect i ve study . These findings , consistent with studies suggesting that testosterone seems to mobilize the abdominal depot on males , suggest that " male pattern " fat distribution may be a misleading description for central adiposity , at least , in men . Degree of maleness as indicated by total and rogen levels is , in fact , negatively associated with central adiposity . However , the role of sex hormone-binding globulin in regulating and rogenic activity warrants further investigation A sub clinical inflammatory reaction has been shown to precede the onset of type 2 ( non-insulin-dependent ) diabetes . We therefore examined prospect ively the effects of the central inflammatory cytokines interleukin (IL)-1beta , IL-6 , and tumor necrosis factor-alpha ( TNF-alpha ) on the development of type 2 diabetes . We design ed a nested case-control study within the prospect i ve population -based European Prospect i ve Investigation into Cancer and Nutrition (EPIC)-Potsdam study including 27,548 individuals . Case subjects were defined to be those who were free of type 2 diabetes at baseline and subsequently developed type 2 diabetes during a 2.3-year follow-up period . A total of 192 cases of incident type 2 diabetes were identified and matched with 384 non-disease-developing control subjects . IL-6 and TNF-alpha levels were found to be elevated in participants with incident type 2 diabetes , whereas IL-1beta plasma levels did not differ between the groups . Analysis of single cytokines revealed IL-6 as an independent predictor of type 2 diabetes after adjustment for age , sex , BMI , waist-to-hip ratio ( WHR ) , sports , smoking status , educational attainment , alcohol consumption , and HbA(1c ) ( 4th vs. the 1st quartile : odds ratio [ OR ] 2.6 , 95 % CI 1.2 - 5.5 ) . The association between TNF-alpha and future type 2 diabetes was no longer significant after adjustment for BMI or WHR . Interestingly , combined analysis of the cytokines revealed a significant interaction between IL-1beta and IL-6 . In the fully adjusted model , participants with detectable levels of IL-1beta and elevated levels of IL-6 had an independently increased risk to develop type 2 diabetes ( 3.3 , 1.7 - 6.8 ) , whereas individuals with increased concentrations of IL-6 but undetectable levels of IL-1beta had no significantly increased risk , both compared with the low-level reference group . These results were confirmed in an analysis including only individuals with HbA(1c ) < 5.8 % at baseline . Our data suggest that the pattern of circulating inflammatory cytokines modifies the risk for type 2 diabetes . In particular , a combined elevation of IL-1beta and IL-6 , rather than the isolated elevation of IL-6 alone , independently increases the risk of type 2 diabetes . These data strongly support the hypothesis that a sub clinical inflammatory reaction has a role in the pathogenesis of type 2 diabetes OBJECTIVE To determine the prospect i ve association between endogenous sex hormones and the development of type 2 diabetes in older men and women . RESEARCH DESIGN AND METHODS A st and ardized medical history was obtained , an oral glucose tolerance test was performed , and plasma sample s for sex hormones and covariates were collected from ambulatory , community-dwelling men and women at baseline from 1984 to 1987 . Approximately 8 years later ( 1992 - 1996 ) , another medical history was obtained , an oral glucose tolerance test was performed , fasting and 2-h insulin levels were measured , and the homeostasis model assessment for insulin resistance ( HOMA-IR ) was evaluated . This report is based on the 294 men and 233 women , aged 55 - 89 years , who completed both visits and who did not have diabetes as determined by history or glucose tolerance test at baseline , as well as women who were postmenopausal and not taking replacement estrogen . RESULTS In age-adjusted correlation analyses , total testosterone was inversely and significantly related to subsequent levels of fasting and postchallenge glucose and insulin in men , whereas bioavailable testosterone and bioavailable estradiol were positively and significantly related to fasting and postchallenge glucose and insulin in women ( all P < 0.05 ) . There was similar significant association with insulin resistance ( HOMA-IR ) in unadjusted and multiply adjusted analyses ( P < 0.05 ) . There were 26 men and 17 women with new ( incident ) diabetes . The odds for new diabetes were 2.7 ( 95 % CI 1.1 - 6.6 ) for men in the lowest quartile of total testosterone and 2.9 ( 1.1 - 8.4 ) for women in the highest quartile of bioavailable testosterone . CONCLUSIONS Low testosterone levels in men and high testosterone levels in women predict insulin resistance and incident type 2 diabetes in older adults This open-label nonr and omized study evaluated the effect of intramuscular testosterone enanthate administration on body composition , protein dynamics , and serum hormone concentrations in seven healthy hypogonadal adults 19 to 47 years old . The subjects had been previously treated with and rogen replacement therapy ( testosterone or gonadotropins ) but underwent a 12-week washout period off all and rogenic therapy prior to study . During the 10-week treatment period , testosterone enanthate ( 100 mg IM ) was administered weekly in the Clinical Research Center . Subjects were instructed to refrain from moderate to heavy exercise for 4 weeks before study and during the treatment period . All were instructed to consume a st and ardized daily diet of 36 kcal/kg/d and 1.5 g/ kg/d protein and 100 % of the recommended dietary allowance for vitamins . Study endpoints were determined before and after testosterone therapy . The primary outcome measure was fat-free mass determined by underwater weighing . Body composition ( fat-free m Abdominal fat distribution is influenced by and rogen levels in both men and women . The purpose of this study was to assess the effects on fat distribution of administering n and rolone decanoate ( ND ; an anabolic steroid with weak and rogenic activity ) or spironolactone ( SP ; an anti and rogen ) in obese postmenopausal women . The design was a r and omized , placebo-controlled , 9-month trial with simultaneous calorie restriction for weight loss . Women in all three groups lost comparable amounts of weight , but the ND-treated women gained lean mass relative to the other two groups ( P < 0.0005 ) and lost more body fat than women in the SP group ( P < 0.01 ) . The resting metabolic rate also increased slightly in the ND group . ND treatment produced a gain in visceral fat , as determined by computed tomography scan , and a relatively greater loss of sc abdominal fat . SP-treated women lost significantly less sc fat than the other two groups . Serum cholesterol decreased in the placebo group , but increased slightly in the other two groups ( significant for SP vs. placebo , P < 0.05 ) . High density lipoprotein cholesterol decreased significantly in the ND-treated women . There were no significant changes in fasting glucose or insulin sensitivity . We conclude that administration of exogenous and rogens modulates body composition in obese postmenopausal women and independently affects visceral and sc abdominal fat BACKGROUND Athletes often take and rogenic steroids in an attempt to increase their strength . The efficacy of these substances for this purpose is unsubstantiated , however . METHODS We r and omly assigned 43 normal men to one of four groups : placebo with no exercise ; testosterone with no exercise ; placebo plus exercise ; and testosterone plus exercise . The men received injections of 600 mg of testosterone enanthate or placebo weekly for 10 weeks . The men in the exercise groups performed st and ardized weight-lifting exercises three times weekly . Before and after the treatment period , fat-free mass was determined by underwater weighing , muscle size was measured by magnetic resonance imaging , and the strength of the arms and legs was assessed by bench-press and squatting exercises , respectively . RESULTS Among the men in the no-exercise groups , those given testosterone had greater increases than those given placebo in muscle size in their arms ( mean [ + /-SE ] change in triceps area , 424 + /- 104 vs. -81 + /- 109 square millimeters ; P < 0.05 ) and legs ( change in quadriceps area , 607 + /- 123 vs. -131 + /- 111 square millimeters ; P < 0.05 ) and greater increases in strength in the bench-press ( 9 + /- 4 vs. -1 + /- 1 kg , P < 0.05 ) and squatting exercises ( 16 + /- 4 vs. 3 + /- 1 kg , P < 0.05 ) . The men assigned to testosterone and exercise had greater increases in fat-free mass ( 6.1 + /- 0.6 kg ) and muscle size ( triceps area , 501 + /- 104 square millimeters ; quadriceps area , 1174 + /- 91 square millimeters ) than those assigned to either no-exercise group , and greater increases in muscle strength ( bench-press strength , 22 + /- 2 kg ; squatting-exercise capacity , 38 + /- 4 kg ) than either no-exercise group . Neither mood nor behavior was altered in any group . CONCLUSIONS Supraphysiologic doses of testosterone , especially when combined with strength training , increase fat-free mass and muscle size and strength in normal men And rogen deficiency in women is increasingly recognized as a new clinical syndrome and has raised our awareness of the importance of accurate and well-vali date d measurements of serum free testosterone ( T ) concentrations in women . Therefore , we compared serum free T levels measured by equilibrium dialysis to those measured by a direct RIA ( analog method ) and to those calculated from the law of mass action ( requires the measurement of total T and SHBG ) . We also calculated the free and rogen index , 100 x T/SHBG , as a simple index known to correlate with free T. Subjects were 147 women with variable and rogen and estrogen statuses . All were studied three times in 1 month and included women 1 ) with regular menses ( estrogen positive , T positive ) , 2 ) more than 50 yr old and not receiving estrogen ( estrogen negative , T positive ) , 3 ) receiving estrogen ( estrogen positive , T negative ) , and 4 ) with severe and rogen deficiency secondary to hypopituitarism ( estrogen negative , T negative ) . Calculated values for free T using the laws of mass action correlated well with those obtained from equilibrium dialysis ( r = 0.99 ; P < 0.0001 ) . However , the agreement depended strongly on the specific assays used for total T and SHBG . In contrast , the direct RIA method had unacceptably high systematic bias and r and om variability and did not correlate as well with equilibrium dialysis values ( r = 0.81 ; P < 0.0001 ) . In addition , the lower limit of detection was higher for the direct RIA than for equilibrium dialysis or calculated free T. Free and rogen index correlates well with free T by equilibrium dialysis ( r = 0.93 ; P < 0.0001 ) , but is a unitless number without reference to the physical reality of free T. We conclude that the mass action equation and equilibrium dialysis are the preferred methods for use in diagnosing and rogen deficiency in women Testosterone ( T ) therapy for hypogonadal men should correct the clinical abnormalities of T deficiency , including improvement of sexual function , increase in muscle mass and strength , and decrease in fat mass , with minimal adverse effects . We have shown that administration of a new transdermal T gel formulation to hypogonadal men provided dose proportional increases in serum T levels to the normal adult male range . We now report the effects of 180 days of treatment with this 1 % T gel preparation ( 50 or 100 mg/day , contained in 5 or 10 g gel , respectively ) compared to those of a permeation-enhanced T patch ( 5 mg/day ) on defined efficacy parameters in 227 hypogonadal men . In the T gel groups , the T dose was adjusted up or down to 75 mg/day ( contained in 7.5 g gel ) on day 90 if serum T concentrations were below or above the normal male range . No dose adjustment was made with the T patch group . Sexual function and mood changes were monitored by question naire , body composition was determined by dual energy x-ray absorptiometry , and muscle strength was measured by the one repetitive maximum technique on bench and leg press exercises . Sexual function and mood improved maximally on day 30 of treatment , without differences across groups , and showed no further improvement with continuation of treatment . Mean muscle strength in the leg press exercise increased by 11 to 13 kg in all treatment groups by 90 days and did not improve further at 180 days of treatment . Moderate increases were also observed in arm/chest muscle strength . At 90 days of treatment , lean body mass increased more in the 100 mg/day T gel group ( 2.74 + /- 0.28 kg ; P = 0.0002 ) than in the 50 mg/day T gel ( 1.28 + /- 0.32 kg ) and T patch groups ( 1.20 + /- 0.26 kg ) . Fat mass and percent fat were not significantly decreased in the T patch group , but showed decreases in the T gel groups ( 50 mg/day , -0.90 + /- 0.32 kg ; 100 mg/day , - 1.05 + /- 0.22 kg ) . The increase in lean mass and the decrease in fat mass were correlated with the changes in average serum T levels attained after transdermal T replacement . These beneficial effects of T replacement were accompanied by the anticipated increases in hematocrit and hemoglobin but without significant changes in the lipid profile . The increase in mean serum prostate-specific antigen levels ( within the normal range ) was correlated with serum levels of T. The greatest increases were noted in the 100 mg/day T gel group . Skin irritation was reported in 5.5 % of subjects treated with T gel and in 66 % of subjects in the permeation-enhanced T patch group . We conclude that T gel replacement improved sexual function and mood , increased lean mass and muscle strength ( principally in the legs ) , and decreased fat mass in hypogonadal men with less skin irritation and discontinuation compared with the recommended dose of the permeation-enhanced T patch OBJECTIVE Accumulating evidence suggests that hyper and rogenemia may be a risk factor for coronary heart disease ( CHD ) in women . The present study was carried out to test the hypothesis that hyper and rogenemia is associated with type 2 diabetes in women and thus may contribute to the increased risk of CHD in women with type 2 diabetes . RESEARCH DESIGN AND METHODS Sex hormones , sex hormone-binding globulin ( SHBG ) , and risk factors for CHD were measured in 20 postmenopausal women with type 2 diabetes and in 29 control subjects . All of the diabetic and control subjects were Hispanic women aged > 55 years who were not taking hormone replacement therapy lipid-lowering drugs , or insulin and who were otherwise r and omly chosen from a cohort of stroke-free subjects from the Northern Manhattan Stroke Study RESULTS Mean age , BMI , total cholesterol , LDL cholesterol , HDL cholesterol , triglycerides , blood pressure , and smoking were not significantly different between cases and control subjects , but waist-to-hip ratio ( WHR ) was significantly higher in the diabetic subjects ( P = 0.01 ) . The mean levels of free testosterone ( FT ) ( P = 0.01 ) , dehydroepi and rosterone sulfate ( P<0.04 ) , and estradiol ( P = 0.01 ) ( controlled for WHR ) were significantly higher in the diabetic subjects ; with the statistical outliers removed , the testosterone ( P = 0.05 ) and and rostenedione ( P = 0.002 ) levels ( controlled for WHR ) were also significantly higher in the diabetic subjects . The mean levels of estrone , cortisol , and SHBG were not significantly different . The results were similar in the 10 diabetic subjects treated with diet only Significant positive correlations ( controlled for age and BMI ) were observed between FT or testosterone and cholesterol , LDL cholesterol , and blood pressure . CONCLUSIONS Postmenopausal Hispanic women with type 2 diabetes had both hyper and rogenemia and hyperestrogenemia , and testosterone or FT correlated positively with risk factors for CHD . Hyper and rogenemia may be a link between diabetes and CHD in women OBJECTIVE : To examine the association between baseline testosterone levels and changes in visceral adiposity in Japanese-American men . DESIGN : Prospect i ve observational study .SUBJECTS : Second-generation Japanese-American males enrolled in a community-based population study . MEASUREMENTS : At baseline , 110 men received a 75 g oral glucose tolerance test ( OGTT ) , and an assessment of body mass index ( BMI ) ; visceral adiposity measured as intra-abdominal fat area ( IAF ) using computed tomography ( CT ) ; fasting insulin and C-peptide levels ; and total testosterone levels . IAF was re-measured after 7.5 y. Subcutaneous fat areas were also measured by CT in the abdomen , thorax and thigh . The total fat ( TF ) was calculated as the sum of IAF and total subcutanous fat areas ( SCF ) . RESULTS : After 7.5 y , IAF increased by a mean of 8.0 cm2 ( 95 % CI : 0.8 , 15.3 ) . Baseline total testosterone was significantly correlated with change in IAF ( r=−0.26 , P=0.006 ) , but not to any appreciable degree with change in BMI , TF , or SCF . In a linear regression model with change in IAF as the dependent variable , baseline testosterone was significantly related to this outcome while adjusting for baseline IAF , SCF , BMI , age , diabetes mellitus status ( OGTT by the WHO diagnostic criteria ) and fasting C-peptide ( regression coefficient for baseline testosterone [ nmol/l;[equals;−107.13 , P=0.003 ) . CONCLUSIONS : In this Japanese-American male cohort , lower baseline total testosterone independently predicts an increase in IAF . This would suggest that by predisposing to an increase in visceral adiposity , low levels of testosterone may increase the risk of type 2 diabetes mellitus An association between sex hormone-binding globulin ( SHBG ) and insulin resistance expressed by the homeostasis model ( HOMA-R ) , and the significance of both variables as risk factors for the development of type 2 diabetes were investigated in 483 Japanese-American subjects . The serum SHBG level was significantly higher in women ( 68.7 nmol/l ) than in men ( 45.1 nmol/l ) . This difference was also significant independently of age , body mass index ( BMI ) , waist to hip ratio ( WHR ) , and HOMA-R. When multiple regression analysis was performed after adjustment for age and BMI , SHBG was not correlated with HOMA-R in men . In women , SHBG was not significantly correlated with HOMA-R after adjustment for age , BMI , and WHR . In a 3-year prospect i ve analysis , HOMA-R was significantly higher in converters to type 2 diabetes than non-converters in both men and women which was independent of age , BMI and WHR . However , after adjusting these variables , SHBG was not a significant risk factor either in men or women . These results indicate that SHBG might be related to insulin resistance secondarily via BMI and /or WHR in both men and women among Japanese-Americans . HOMA-R is a useful index for both men and women as a risk factor of type 2 diabetes when only fasting blood sample s can be obtained OBJECTIVES Previous studies have suggested that abnormal levels of cortisol and testosterone might increase the risk of serious somatic diseases . To test this hypothesis , we conducted a 5-year follow-up study in middle-aged men . METHODS A population -based cohort study conducted in 1995 amongst 141 Swedish men born in 1944 , in whom a clinical examination supplemented by medical history aim ed to disclose the presence of cardiovascular disease ( CVD ) ( myocardial infa rct ion , angina pectoris , stroke ) , type 2 diabetes and hypertension were performed at baseline and at follow-up in the year 2000 . In addition , salivary cortisol levels were measured repeatedly over the day . Serum testosterone concentrations were also determined . Using the baseline data , an algorithm was constructed , which classified the secretion pattern of cortisol and testosterone from each individual as being normal or abnormal . RESULTS By the end of follow-up , men with an abnormal hormone secretion pattern ( n = 73 ) had elevated mean arterial pressure ( P = 0.003 ) , fasting insulin ( P = 0.009 ) and insulin : glucose ratio ( P = 0.005 ) compared with men with a normal secretion pattern ( n = 68 ) . Body mass index , waist circumference , and waist : hip ratio were significantly elevated in both groups . However , the 5-year incidence of CVD , type 2 diabetes , and hypertension were significantly higher ( P < 0.001 ) in men with an abnormal neuroendocrine secretory pattern compared to men with a normal pattern . CONCLUSIONS These data suggest that an abnormal neuroendocrine secretory pattern is prospect ively associated with an increased incidence of cardiovascular-related events and type 2 diabetes The results of recent studies suggest that a relative hypogonadism in men is associated with several established risk factors for prevalent diseases . Therefore , we determined total and free testosterone , luteinizing hormone ( LH ) , and sex-hormone binding globulin ( SHBG ) in a cohort of r and omly selected men ( n = 659 ) at 67 years of age . These data were analyzed cross-sectionally in relation to blood glucose and serum insulin , which were measured while fasting and after an oral glucose tolerance test , in addition to plasma lipids and blood pressure . The data were also analyzed in relation to impaired glucose tolerance ( IGT ) and diabetes , which were discovered at examination or earlier diagnosis . Risk factors for the development of diabetes up to 80 years of age were analyzed with univariate and multivariate statistics . Total and free testosterone and SHBG concentrations correlated negatively with glucose and insulin values ; total testosterone and SHBG , with triglycerides ; and SHBG , with blood pressure ( from P < 0.05 to P < 0.01 ) . Men with IGT or newly diagnosed diabetes had higher BMI values ( 26.2 ± 0.31 and 27.0 ± 0.59 [ mean ± SE ] , respectively ) and waist circumference ( 99.0 ± 1.03 and 100.5 ± 1.57 ) than nondiabetic men ( BMI , 25.1 ± 0.14 ; waist circumference , 95.4 ± 0.47 ; P < 0.05 ) , indicating abdominal obesity . Such men and men with previously diagnosed diabetes had , in general , lower total and free testosterone and SHBG levels , while those for LH were not different . In multivariate analyses that included BMI , waist-to-hip ratio , total and free testosterone , and SHBG , the remaining independent predictors for the development of diabetes were low total testosterone ( P = 0.015 ) and , on the borderline , low SHBG ( P = 0.053 ) . In relation to nondiabetic men , the risk ratio for mortality , myocardial infa rct ion , and stroke increased gradually and significantly from 1.18 to 1.68 , from 1.51 to 1.78 , and from 1.72 to 2.46 in men with IGT , newly diagnosed diabetes , and previously known diabetes , respectively . It was concluded that low testosterone and SHBG concentrations in elderly men are associated with established risk factors for diabetes and in established diabetes . Moreover , low testosterone levels independently predict the risk of developing diabetes . In different degrees of expression , the diabetic state predicts strongly ( and gradually mortality from ) myocardial infa rct ion and stroke . It has been suggested that a relative hypogonadism might be a primary event , because other studies have shown that testosterone deficiency is followed by insulin resistance , which is ameliorated by testosterone substitution . The data suggest that the relative hypogonadism involved might be of both central and peripheral origin Summary Plasma insulin is a risk factor for diabetes mellitus and cardiovascular disease in men . We investigated the association between plasma testosterone and plasma insulin in an occupational sample of 1292 healthy adult men . Total plasma testosterone decreased with each decade of age and insulin increased with each decade of age . In these cross-sectional data , this significant grade d inverse association between testosterone and insulin was independent of age . The association was reduced but not explained by the addition of obesity and subscapular skinfold to the model . Adjustment for alcohol consumption , cigarette smoking and plasma glucose did not material ly alter the association . These results are the reverse of the positive association of and rogens with insulin in women and suggest alternative possible explanations for the effect of hyperinsulinaemia on cardiovascular disease risk . Prospect i ve studies will be necessary to determine the direction and causal nature of this association The effects of testosterone treatment of abdominally obese men have been assessed by evaluating the following parameters : The metabolic activity of different adipose tissue regions in vivo ( using lipid label as a tracer ) and in vitro ( measuring lipoprotein lipase ( LPL ) activity ) , the total and visceral adipose tissue mass , insulin sensitivity , fasting blood glucose , blood lipids , and blood pressure as well as prostate volume . Middle-aged men with abdominal obesity were treated with transdermal administration of testosterone ( T ) , dihydrotestosterone ( DHT ) or placebo ( P ) during 9 months . The study was double-blind . Treatment with T was followed by an inhibited uptake of lipid label in adipose tissue triglycerides , a decreased LPL-activity and an increased turn-over rate of lipid label in the abdominal adipose tissue region in comparisons with the DHT and P groups . These effects on adipose tissue metabolism were not detected in the femoral adipose tissue region in any of the groups . T treatment was also followed by a specific decrease of visceral fat mass ( measured by CT-scan ) , by increased insulin sensitivity ( measured with the euglycemic glucose clamp ) , by a decrease in fasting blood glucose , plasma cholesterol and triglycerides as well as a decrease in diastolic blood pressure . In the DHT group an increased visceral mass was detected . No other changes in these variables were found in the DHT and P groups . There were no detectable changes in prostate volume ( measured by ultra-sound ) , prostate specific antigen concentration , genito-urinary history or urinary flow measurements in any of the groups . It is suggested that T substitution to a selected group of men results in general metabolic and circulatory improvements . The prostate area needs further careful attention Studies on regional differences of adipose tissue metabolism have mainly been performed in vitro . To allow measurements of lipid uptake in vivo in man , radioactive label from [9,10 - 3H]oleic acid in 80 g orally administered milk fat was measured after 4 h in abdominal and femoral sc adipose tissues in 28 middle-aged , abdominally obese men . Radioactivity was measured in adipose tissue triglycerides extracted from needle biopsies . Lipoprotein lipase ( LPL ) activity was also measured . Uptake of label in triglycerides and LPL activity were higher ( 20 % and 15 % , respectively ; P < 0.05 ) in the abdominal compared to the femoral adipose tissue region . The men were then r and omly assigned to three groups , receiving testosterone ( T ) , dihydrotestosterone , or placebo , for 9 months . After 2 months of treatment , the procedure of administration of label was repeated , this time using [U-14C]oleic acid as a marker . Measurements of radioactive label was then performed after 4 h and monthly up to 7 months . Supplementation with T was followed by an inhibited uptake of label in triglycerides ( 34 % ; P < 0.05 ) , lower LPL activity ( 48 % ; P < 0.05 ) , and a shorter t1/2 ( 30 % ; P < 0.05 ) in the abdominal adipose tissue region compared with the dihydrotestosterone and placebo groups . No significant effect of T on triglyceride uptake , LPL activity , or t1/2 was found in sc femoral adipose tissue . It was concluded that the turnover rate of depot triglycerides is more rapid in abdominal compared to femoral sc adipose tissue in men . Furthermore , T supplementation inhibits triglyceride uptake and LPL activity and causes a more rapid turnover of triglycerides only in the sc abdominal adipose tissue region . These results demonstrate the marked effects of T on adipose tissue metabolism in vivo and suggest that T is an important regulator of the proportion of depot fat mass in central and peripheral adipose tissue in men As men age , serum testosterone concentrations decrease , the percentage of body mass that is fat increases , the percentage of lean body mass decreases , and muscle strength decreases . Because these changes are similar to those that occur in hypogonadal men , we hypothesized that increasing the serum testosterone concentration of men over 65 yr of age to that in young men would decrease their fat mass , increase their lean mass , and increase their muscle strength . We r and omized 108 men over 65 yr of age to wear either a testosterone patch or a placebo patch in a double blind study for 36 months . We measured body composition by dual energy x-ray absorptiometry and muscle strength by dynamometer before and during treatment . Ninety-six men completed the entire 36-month protocol . Fat mass decreased ( -3.0+/-0.5 kg ) in the testosterone-treated men during the 36 months of treatment , which was significantly different ( P = 0.001 ) from the decrease ( -0.7+/-0.5 kg ) in the placebo-treated men . Lean mass increased ( 1.9+/-0.3 kg ) in the testosterone-treated men , which was significantly different ( P < 0.001 ) from that ( 0.2+/-0.2 kg ) in the placebo-treated men . The decrease in fat mass in the testosterone-treated men was principally in the arms ( -0.7+/-0.1 kg ; P < 0.001 compared to the placebo group ) and legs ( -1.1+/-0.2 kg ; P < 0.001 ) , and the increase in lean mass was principally in the trunk ( 1.9+/-0.3 kg ; P < 0.001 ) . The change in strength of knee extension and flexion at 60 degrees and 180 degrees angular velocity during treatment , however , was not significantly different between the two groups . We conclude that increasing the serum testosterone concentrations of normal men over 65 yr of age to the midnormal range for young men decreased fat mass , principally in the arms and legs , and increased lean mass , principally in the trunk , but did not increase the strength of knee extension and flexion , as measured by dynamometer P oral estrogen therapy exerts beneficial effects on serum lipids,1 providing one of the mechanisms used to explain the decreased cardiovascular risk associated with hormone replacement therapy ( HRT ) in observational studies ( e.g. , in the Nurses ’ Health Study 2 ) . However , recent r and omized clinical trials using estrogen – progestin combinations3–5 have changed the picture , and oral HRT is no longer recommended for cardiovascular prevention . The results of the estrogen arm of the Womens ’ Health Initiative study 4 are pending ; the jury is still out on the possible benefits of estrogen alone . Irrespective of the cardiovascular effects , HRT will continue to be used for the control of postmenopausal symptoms and questions of safety will persist . Oral and transdermal HRT result in quantitatively and qualitatively different lipid and other metabolic effects result ing from hepatic first-pass metabolism during oral therapy,6 as well as from different quantities of estrogen introduced into the body by the 2 routes of administration . The aim of the present investigation was to compare the effects of oral and transdermal HRT on serum lipids , glucose , and insulin as well as the novel cardiovascular risk factor serum highly sensitive C-reactive protein ( hs-CRP7 ) in healthy postmenopausal women . • • • Healthy postmenopausal white women were recruited for the study and all gave informed consent to participate in the study . The local ethics committee approved the study . The women were r and omly assigned to receive either oral or transdermal HRT . Details of the study procedures have been published earlier.8,9 For the present analysis , we included 64 participants for whom serum lipid and hs-CRP values at baseline and after 6 months were available . Thirtytwo women received transdermal estrogen and sequential progestin therapy in the form of 2 weeks of estradiol ( 50 g/day ) followed by 2 weeks of estradiol ( 50 g/day)/norethisterone acetate ( NETA , 0.25 mg/ day ) ( Estracomb ; Novartis Pharma AG , Basel , Switzerl and ) . Patches were changed twice a week . Another 32 women received continuous peroral estradiol ( 2 mg/day ) for the first 12 days , combined with cyclic peroral NETA ( 1 mg/day ) for the next 10 days , followed by estradiol ( 1 mg/day ) for 6 days ( Trisekvens ; Novo Nordisk , Copenhagen , Denmark ) . Both treatments led to similar increases in plasma estradiol levels.9 They also reduced climacteric symptoms and caused regular withdrawal bleeding,9 confirming compliance with the treatments . Blood sample s were obtained with venipuncture after an overnight fast at baseline and after 6 months ’ treatment during the last days of estradiol NETA intake . Plasma glucose , insulin , and serum lipids including total cholesterol , high-density lipoprotein ( HDL ) cholesterol , triglycerides , and lipoprotein(a ) ( Lp[a ] ) were measured with st and ard methods . Low-density lipoprotein ( LDL ) cholesterol was calculated according to Friedewald ’s formula . Serum hs-CRP was measured as described earlier.10 Statistical analyses were performed with NCSS statistical program ( www.ncss.com ; Number Cruncher Statistical Systems , Kaysville , Utah ) using descriptive statistics , correlation analysis , analysis of covariance , and stepwise multivariate analysis . Because of the skewed distribution of serum triglycerides , Lp(a ) , and hs-CRP , logarithmic transformation of values was used where appropriate . In some of the analyses , only hs-CRP values 10 mg/L were included to exclude the effect of possible intervening infection . Nonparametric tests were used for statistical comparisons between groups . A p value 0.05 was considered statistically significant . Except for smoking and serum HDL-3 cholesterol , the groups were well balanced at baseline ( Table 1 ) . At baseline , hs-CRP correlated positively with body mass index ( r 0.34 , p 0.007 ) and plasma insulin ( r 0.36 , p 0.004 ) , but not with any other variables . hs-CRP did not differ significantly between smokers ( n 20 ) and nonsmokers ( n 44 ) ( 1.27 1.22 vs 1.28 1.19 mg/L [ mean SD ] ; p 0.36 ) . Effects of the 2 treatments on serum lipids and hs-CRP during 6 months are listed in Table 2 . In the analyses adjusted for age , smoking , body mass index , and baseline log-transformed hs-CRP as covariates , oral HRT was significantly associated with an hs-CRP increase ( p 0.02 ) . In the analysis of covariance , with baseline log-transformed hs-CRP as covariate and a single hs-CRP value 10 mg/L excluded , oral HRT was associated with a greater log-transformed hs-CRP increase during 6 months of therapy than transdermal HRT ( 0.20 0.05 vs 0.06 0.05 [ mean SE ] ; p 0.03 ) . We also investigated factors related to hs-CRP change ( log-transformed , the single outlier excluded ) From the Departments of Medicine and Gynecology and Obstetrics , University of Helsinki , Helsinki , Finl and . This study was supported by grants from the Finnish Academy of Science and from the Research Council of Novartis Pharma , Helsinki , Finl and . Novartis also supplied the study medications . Dr. Str and berg is supported by Grant 48613 from the Academy of Finl and , Helsinki , Finl and . Dr. Str and berg ’s address is : Department of Medicine , Geriatric Clinic , University of Helsinki , PO Box 340 , FIN-00029 HUS , Finl and . E-mail : timo.str and [email protected] . Manuscript received February 6 , 2003 ; revised manuscript received and accepted April 7 , 2003 Background : Low serum testosterone is associated with several cardiovascular risk factors including dyslipidaemia , adverse clotting profiles , obesity , and insulin resistance . Testosterone has been reported to improve symptoms of angina and delay time to ischaemic threshold in unselected men with coronary disease . Objective : This r and omised single blind placebo controlled crossover study compared testosterone replacement therapy ( Sustanon 100 ) with placebo in 10 men with ischaemic heart disease and hypogonadism . Results : Baseline total testosterone and bioavailable testosterone were respectively 4.2 ( 0.5 ) nmol/l and 1.7 ( 0.4 ) nmol/l . After a month of testosterone , delta value analysis between testosterone and placebo phase showed that mean ( SD ) trough testosterone concentrations increased significantly by 4.8 ( 6.6 ) nmol/l ( total testosterone ) ( p = 0.05 ) and 3.8 ( 4.5 ) nmol/l ( bioavailable testosterone ) ( p = 0.025 ) , time to 1 mm ST segment depression assessed by Bruce protocol exercise treadmill testing increased by 74 ( 54 ) seconds ( p = 0.002 ) , and mood scores assessed with vali date d question naires all improved . Compared with placebo , testosterone therapy was also associated with a significant reduction of total cholesterol and serum tumour necrosis factor α with delta values of −0.41 ( 0.54 ) mmol/l ( p = 0.04 ) and −1.8 ( 2.4 ) pg/ml ( p = 0.05 ) respectively . Conclusion : Testosterone replacement therapy in hypogonadal men delays time to ischaemia , improves mood , and is associated with potentially beneficial reductions of total cholesterol and serum tumour necrosis factor α In this study , we vali date d measurements of free testosterone ( fT ) and free estradiol ( fE(2 ) ) concentrations calculated from total serum concentrations of testosterone ( T ) , estradiol ( E(2 ) ) , and sex hormone-binding globulin ( SHBG ) , measured by direct , commercial radioimmunoassays , by comparison with reference measurements obtained by dialysis plus an in-house radioimmunoassay after extraction and chromatographic purification . The study was conducted in serum sample s from 19 postmenopausal women who were part of an ongoing prospect i ve cohort study . We also performed sensitivity analyses to examine the robustness of the theoretical calculations . Sensitivity analyses showed that in this population , competitive binding of dihydrotestosterone and total T could be ignored in the calculation of fE(2 ) , and competitive binding by dihydrotestosterone does not need to be taken into account for calculation of fT. Furthermore , variations in albumin and SHBG concentrations had negligible effects on fT and fE(2 ) calculations . Values of fT and fE(2 ) , calculated from total T and E(2 ) concentrations obtained by the same in-house radioimmunoassay used for the dialysis method , correlated highly with the measurements by dialysis ( Pearson 's coefficients of correlation above 0.97 ) . When calculating fT and fE(2 ) using total T and total E(2 ) concentrations obtained by different direct radioimmunoassays , almost all kits gave good correlations with the reference method for fT ( Pearson 's r > 0.83 ) , but only a few gave good correlations for fE(2 ) ( Diagnostic System Laboratories and DiaSorin ; r > 0.80 ) . The direct radioimmunoassays giving the best correlation for fT and fE(2 ) with the dialysis method were those that best measured total concentrations of T and E(2 ) . Furthermore , mean values of fT and fE(2 ) corresponded well to mean values by the reference method if SHBG measurements were also well calibrated . We conclude that in postmenopausal women , theoretical calculations are valid for the determination of fT and fE(2 ) concentrations and can give reliable estimation of cancer risk in epidemiological studies when the total concentrations of T , E(2 ) , and SHBG are measured accurately Treatment of hypogonadal men with testosterone has been shown to ameliorate the effects of testosterone deficiency on bone , muscle , erythropoiesis , and the prostate . Most previous studies , however , have employed somewhat pharmacological doses of testosterone esters , which could result in exaggerated effects , and /or have been of relatively short duration or employed previously treated men , which could result in dampened effects . The goal of this study was to determine the magnitude and time course of the effects of physiological testosterone replacement for 3 yr on bone density , muscle mass and strength , erythropoiesis , prostate volume , energy , sexual function , and lipids in previously untreated hypogonadal men . We selected 18 men who were hypogonadal ( mean serum testosterone + /- SD , 78 + /- 77 ng/dL ; 2.7 + /- 2.7 nmol/L ) due to organic disease and had never previously been treated for hypogonadism . We treated them with testosterone transdermally for 3 yr . Sixteen men completed 12 months of the protocol , and 14 men completed 36 months . The mean serum testosterone concentration reached the normal range by 3 months of treatment and remained there for the duration of treatment . Bone mineral density of the lumbar spine ( L2-L4 ) increased by 7.7 + /- 7.6 % ( P < 0.001 ) , and that of the femoral trochanter increased by 4.0 + /- 5.4 % ( P = 0.02 ) ; both reached maximum values by 24 months . Fat-free mass increased 3.1 kg ( P = 0.004 ) , and fat-free mass of the arms and legs individually increased , principally within the first 6 months . The decrease in fat mass was not statistically significant . Strength of knee flexion and extension did not change . Hematocrit increased dramatically , from mildly anemic ( 38.0 + /- 3.0 % ) to midnormal ( 43.1 + /- 4.0 % ; P = 0.002 ) within 3 months , and remained at that level for the duration of treatment . Prostate volume also increased dramatically , from subnormal ( 12.0 + /- 6.0 mL ) before treatment to normal ( 22.4 + /- 8.4 mL ; P = 0.004 ) , principally during the first 6 months . Self-reported sense of energy ( 49 + /- 19 % to 66 + /- 24 % ; P = 0.01 ) and sexual function ( 24 + /- 20 % to 66 + /- 24 % ; P < 0.001 ) also increased , principally within the first 3 months . Lipids did not change . We conclude from this study that replacing testosterone in hypogonadal men increases bone mineral density of the spine and hip , fat-free mass , prostate volume , erythropoiesis , energy , and sexual function . The full effect of testosterone on bone mineral density took 24 months , but the full effects on the other tissues took only 3 - 6 months . These results provide the basis for monitoring the magnitude and the time course of the effects of testosterone replacement in hypogonadal men OBJECTIVE To examine the impact of a 12-week walking program on body composition and risk factors for cardiovascular disease in women with type 2 diabetes and in normoglycemic women with first-degree diabetic relatives . RESEARCH DESIGN AND METHODS There were 11 postmenopausal women with type 2 diabetes and 20 normoglycemic women of similar age and BMI who were asked to walk 1 h per day on 5 days each week for 12 weeks . Fitness ( estimated VO2max ) was assessed with a 1.6-km walking test ; body composition was measured by dual-energy X-ray absorptiometry ; and sex hormone , metabolic , and lipid concentrations were measured in serum . RESULTS After 12 weeks , estimated VO2max improved in both groups ( P < 0.005 ) . In the diabetic women , BMI and fat content of the upper body and and roid waist region decreased ( P < 0.05 ) . Concentrations of fasting blood glucose ( P < 0.05 ) HbAlc ( P < 0.05 ) , total cholesterol ( P < 0.005 ) , and LDL cholesterol ( P < 0.05 ) decreased , while HDL cholesterol and sex hormones were unchanged . In contrast , normoglycemic women failed to lose body fat after 12 weeks of exercise in a walking program . However , their HbAlc , total cholesterol , LDL cholesterol , sex hormone-binding globulin , and total testosterone concentrations decreased ( P < 0.05 ) . On pooling the data and including diabetes as a categorical grouping variable , stepwise multiple regression analysis indicated that the change in central ized body fat , but not the change in VO2max , was related to change in fasting blood glucose . CONCLUSIONS Twelve weeks of walking increased the fitness of diabetic and normoglycemic women . Improvement of fasting blood glucose was related to the loss of central ized body fat rather than to improved fitness Serum sex-hormone-binding globulin ( SHBG ) and corticosteroid-binding globulin ( CBG ) concentrations were evaluated as risk factors for the development of non-insulin-dependent diabetes mellitus ( NIDDM ) , myocardial infa rct ion , stroke , and premature death in a prospect i ve study of 1462 r and omly selected women , aged 38–60 yr , over 12 yr of observation . In multivariate analysis , taking only age into consideration as a confounding factor , low initial concentration of SHBG was significantly correlated to the incidence of NIDDM and stroke , and high initial concentration of CBG was correlated to the incidence of NIDDM . There were also significant correlations between SHBG and CBG concentrations on one h and and possible risk factors for the end points studied , such as serum triglycerides , serum cholesterol , fasting blood glucose , body mass , body mass index , waist/hip ratio , smoking habits , and systolic blood pressure , on the other . When these possible confounders , in addition to age , were taken into consideration in multivariate analyses , only the inverse significant correlation between SHBG and NIDDM remained . The increased incidence of diabetes was confined to the lowest quintile of SHBG values , where it was 5-fold higher than in the remaining group . This incidence was further increased to 8- and 11-fold in the lowest 10 and 5 % of the values , respectively . We conclude that SHBG is a uniquely strong independent risk factor for the development of NIDDM in women And rogen therapy may precipitate obstructive sleep apnea in men . Despite increasing and rogen use in older men , few studies have examined sleep and breathing . R and omized , double-blind , placebo-controlled studies examining effects of testosterone simultaneously on sleep , breathing , and function in older men are not available . Seventeen community-dwelling healthy men over the age of 60 yr were r and omized to receive three injections of i m testosterone esters at weekly intervals ( 500 mg , 250 mg , and 250 mg ) or matching oil-based placebo and then crossed over to the other treatment after 8 wk of washout . Polysomnography , anthropometry , and physical , mental , and metabolic function were assessed at baseline and after each treatment period . Testosterone treatment reduced total time slept ( approximately 1 h ) , increased the duration of hypoxemia ( approximately 5 min/night ) , and disrupted breathing during sleep ( total and non-rapid eye movement respiratory disturbance indices both increased by approximately seven events per hour ) ( all P < 0.05 ) . Despite expected effects on body composition ( increase in total and lean mass , reduction in fat mass , P < 0.05 , bioimpedance method ) , upper airway dimensions did not change ( acoustic reflectometry ) . Driving ability ( computer simulation ) , physical activity ( accelerometry , Physical Activity Scale in the Elderly ) , quality of life ( SF36 , Functional Outcomes of Sleep Question naire ) , mood ( Profile of Mood States Question naire ) , sleepiness ( Epworth , Stanford scales ) , and insulin resistance ( homeostasis model ) also were not changed by treatment . Short-term administration of high-dose testosterone shortens sleep and worsens sleep apnea in older men but did not alter physical , mental , or metabolic function . These changes did not appear to be due to upper airway narrowing . Further study of longer-term lower-dose and rogen therapy on sleep and breathing is needed to evaluate its safety in older men CONTEXT Previous studies of testosterone supplementation in HIV-infected men failed to demonstrate improvement in muscle strength . The effects of resistance exercise combined with testosterone supplementation in HIV-infected men are unknown . OBJECTIVE To determine the effects of testosterone replacement with and without resistance exercise on muscle strength and body composition in HIV-infected men with low testosterone levels and weight loss . DESIGN AND SETTING Placebo-controlled , double-blind , r and omized clinical trial conducted from September 1995 to July 1998 at a general clinical research center . PARTICIPANTS Sixty-one HIV-infected men aged 18 to 50 years with serum testosterone levels of less than 12.1 nmol/L ( 349 ng/dL ) and weight loss of 5 % or more in the previous 6 months , 49 of whom completed the study . INTERVENTIONS Participants were r and omly assigned to 1 of 4 groups : placebo , no exercise ( n = 14 ) ; testosterone enanthate ( 100 mg/wk intramuscularly ) , no exercise ( n = 17 ) ; placebo and exercise ( n = 15 ) ; or testosterone and exercise ( n = 15 ) . Treatment duration was 16 weeks . MAIN OUTCOME MEASURES Changes in muscle strength , body weight , thigh muscle volume , and lean body mass compared among the 4 treatment groups . RESULTS Body weight increased significantly by 2.6 kg ( P<.001 ) in men receiving testosterone alone and by 2.2 kg ( P = .02 ) in men who exercised alone but did not change in men receiving placebo alone ( -0.5 kg ; P = .55 ) or testosterone and exercise ( 0.7 kg ; P = .08 ) . Men treated with testosterone alone , exercise alone , or both experienced significant increases in maximum voluntary muscle strength in leg press ( range , 22%-30 % ) , leg curls ( range , 18%-36 % ) , bench press ( range , 19%-33 % ) , and latissimus pulls ( range , 17%-33 % ) . Gains in strength in all exercise categories were greater in men assigned to the testosterone-exercise group or to the exercise-alone group than in those assigned to the placebo-alone group . There was a greater increase in thigh muscle volume in men receiving testosterone alone ( mean change , 40 cm3 ; P<.001 vs zero change ) or exercise alone ( 62 cm3 ; P = .003 ) than in men receiving placebo alone ( 5 cm3 ; P = .70 ) . Average lean body mass increased by 2.3 kg ( P = .004 ) and 2.6 kg ( P<.001 ) , respectively , in men who received testosterone alone or testosterone and exercise but did not change in men receiving placebo alone ( 0.9 kg ; P = .21 ) . Hemoglobin levels increased in men receiving testosterone but not in those receiving placebo . CONCLUSION Our data suggest that testosterone and resistance exercise promote gains in body weight , muscle mass , muscle strength , and lean body mass in HIV-infected men with weight loss and low testosterone levels . Testosterone and exercise together did not produce greater gains than either intervention alone The endocrine-metabolic hallmarks of polycystic ovary syndrome are hyperinsulinism , hyper and rogenism , dyslipidemia , and anovulation . We hypothesized that dyslipidemia and anovulation in nonobese women with polycystic ovary syndrome are essentially secondary to the concerted effects of hyper and rogenism and insulin resistance . We tested this hypothesis by comparing the efficacy of anti- and rogen ( flutamide ) or insulin-sensitizing ( metformin ) monotherapy to that of combined therapy in normalizing the endocrine-metabolic and anovulatory status of nonobese , young women with hyperinsulinemic hyper and rogenism . Thirty-one young women ( mean age , 18.7 yr ; body mass index , 21.9 kg/m(2 ) ; hirsutism score , 16 ; monthly ovulation rate monitored by weekly serum progesterone , 10 % ) were r and omly assigned to receive once daily flutamide ( 250 mg ; n = 10 ) , metformin ( 1275 mg ; n = 8) , or combined flutamide- metformin therapy ( n = 13 ) for 9 months . At baseline , there were no endocrine-metabolic differences among treatment groups . Compared with monotherapy , combined flutamide-metformin therapy result ed in greater improvements in insulin sensitivity , in testosterone , and rostenedione , dehydroepi and rosterone sulfate , and triglyceride levels , and in low-density lipoprotein/high-density lipoprotein-cholesterol ratio ( all P < 0.005 ) . Monthly ovulation rates increased after 9 months to 75 and 92 % , respectively , with metformin alone or with combined therapy , but were unimproved with flutamide alone . All treatments were well tolerated . In conclusion , combined anti- and rogen and insulin-sensitizing treatment in young , nonobese women with hyperinsulinemic hyper and rogenism had additive benefits on insulin sensitivity , hyper and rogenemia , and dyslipidemia . The data from this small study suggest that dyslipidemia is secondary to excess and rogen action in concert with the hyperinsulinemia associated with insulin resistance . In contrast , anovulation seems to be mainly attributable to insulin resistance and hyperinsulinemia We compared the effects of oral estradiol ( 2 mg ) , transdermal estradiol ( 50 microg ) , and placebo on measures of coagulation , fibrinolysis , inflammation and serum lipids and lipoproteins in 27 postmenopausal women at baseline and after 2 and 12 weeks of treatment . Oral and transdermal estradiol induced similar increases in serum free estradiol concentrations . Oral therapy increased the plasma concentrations of factor VII antigen ( FVIIag ) and activated factor VII ( FVIIa ) , and the plasma concentration of the prothrombin activation marker prothrombin fragment 1 + 2 ( F1 + 2 ) . Oral but not transdermal estradiol therapy significantly lowered plasma plasminogen activator inhibitor-1 ( PAI-1 ) antigen and tissue-type plasminogen activator ( tPA ) antigen concentrations and PAI-1 activity , and increased D-dimer concentrations , suggesting increased fibrinolysis . The concentration of soluble E-selectin decreased and serum C-reactive protein ( CRP ) increased significantly in the oral but not in the transdermal or placebo groups . In the oral but not in the transdermal or placebo estradiol groups low-density-lipoprotein ( LDL ) cholesterol , apolipoprotein B and lipoprotein ( a ) concentrations decreased while high-density-lipoprotein ( HDL ) cholesterol , apolipoprotein AI and apolipoprotein All concentrations increased significantly . LDL particle size remained unchanged . In summary , oral estradiol increased markers of fibrinolytic activity , decreased serum soluble E-selectin levels and induced potentially antiatherogenic changes in lipids and lipoproteins . In contrast to these beneficial effects , oral estradiol changed markers of coagulation towards hypercoagulability , and increased serum CRP concentrations . Transdermal estradiol or placebo had no effects on any of these parameters . These data demonstrate that oral estradiol does not have uniformly beneficial effects on cardiovascular risk markers and that the oral route of estradiol administration rather than the circulating free estradiol concentration is critical for any changes to be observed Simultaneous measurements of serum estradiol , testosterone , cortisol , prolactin , total cholesterol ( TC ) , high density lipoprotein cholesterol ( HDLC ) , low density lipoprotein cholesterol ( LDLC ) and triglycerides in Thai men and postmenopausal women aged over 50 years were carried out in four groups of subjects : healthy controls , and patients with essential hypertension , non-insulin dependent diabetes mellitus ( NIDDM ) , and coronary heart disease . Hypertriglyceridemia and hypercholesterolemia were found more often in patients with essential hypertension than in patients with other diseases . Low levels of HDLC with high TC/HDLC and LDLC/HDLC ratios occurred more frequently in coronary heart disease patients . Hypertensive men had the highest plasma estradiol levels while men with coronary heart disease had the least testosterone levels compared with men with the other two diseases . Decreased testosterone and /or increased estradiol may have an adverse effect on lipid profiles in elderly men . However , neither the sex hormones , cortisol , nor prolactin , appeared to have any influence on serum lipids and lipoproteins in elderly women . These findings in the Thai population are consistent with those previously reported in other population |
12,144 | 31,431,975 | A matrix presentation of costs mapped with outcomes indicated increasing costs with either no difference or improvements in clinical effectiveness . | Objective The aim was to appraise and synthesize studies evaluating the clinical and cost effectiveness of conservative interventions for chronic lower extremity musculoskeletal ( MSK ) conditions and describe their characteristics , including the type of economic evaluation , primary outcomes and which conditions .
Conclusion Economic evaluations have been conducted largely for exercise-based interventions for MSK conditions of the hip and knee . | Background Arthroscopic partial meniscectomy ( APM ) is extensively used to relieve pain in patients with symptomatic meniscal tear ( MT ) and knee osteoarthritis ( OA ) . Recent studies have failed to show the superiority of APM compared to other treatments . We aim to examine whether existing evidence is sufficient to reject use of APM as a cost-effective treatment for MT+OA . Methods We built a patient-level microsimulation using Monte Carlo methods and evaluated three strategies : Physical therapy ( ‘ PT ’ ) alone ; PT followed by APM if subjects continued to experience pain ( ‘ Delayed APM ’ ) ; and ‘ Immediate APM ’ . Our subject population was US adults with symptomatic MT and knee OA over a 10 year time horizon . We assessed treatment outcomes using societal costs , quality -adjusted life years ( QALYs ) , and calculated incremental cost-effectiveness ratios ( ICERs ) , incorporating productivity costs as a sensitivity analysis . We also conducted a value-of-information analysis using probabilistic sensitivity analyses . Results Calculated ICERs were estimated to be $ 12,900/QALY for Delayed APM as compared to PT and $ 103,200/QALY for Immediate APM as compared to Delayed APM . In sensitivity analyses , inclusion of time costs made Delayed APM cost-saving as compared to PT . Improving efficacy of Delayed APM led to higher incremental costs and lower incremental effectiveness of Immediate APM in comparison to Delayed APM . Probabilistic sensitivity analyses indicated that PT had 3.0 % probability of being cost-effective at a willingness-to-pay ( WTP ) threshold of $ 50,000/QALY . Delayed APM was cost effective 57.7 % of the time at WTP = $ 50,000/QALY and 50.2 % at WTP = $ 100,000/QALY . The probability of Immediate APM being cost-effective did not exceed 50 % unless WTP exceeded $ 103,000/QALY . Conclusions We conclude that current cost-effectiveness evidence does not support unqualified rejection of either Immediate or Delayed APM for the treatment of MT+OA . The amount to which society would be willing to pay for additional information on treatment outcomes greatly exceeds the cost of conducting another r and omized controlled trial on APM For many years , the National Institute for Health and Care Excellence ( NICE ) has recommended use of the EQ-5D-3L ( 3L ) [ 1 ] and its value set for the UK [ 2 ] . Since 2011 , an exp and ed-level instrument , the EQ-5D-5L ( 5L ) , has been available [ 3 ] and value sets now exist to support its use , including a value set for Engl and [ 4 , 5 ] . This poses a challenge for NICE . Should it recommend the 5L rather than the 3L ? This is neither a trivial nor merely academic matter : the choice of whether to use the 5L ( and English value set ) or the 3L ( and UK value set ) is likely to impact estimates of quality -adjusted life-years ( QALYs ) and incremental cost-effectiveness ratios ( ICERs ) . The size and direction of that impact will depend on the disease and the nature of the health problems . In general , where technologies improve self-reported health , estimates of QALY gains will often be smaller with the 5L [ 6 ] . In contrast , where technologies extend the length of life , estimates of QALY gains will be higher ( to varying degrees ) : each year of additional life is assigned a higher utility . The ultimate impact on health technology assessment ( HTA ) will depend on whether the differences between the 3L and 5L push ICERs from one side of the cost-effectiveness threshold to the other . Given the implication s for NICE ’s technology appraisal process , and other decisions informed by EQ-5D data , the Department of Health for Engl and has called for an independent validation of the 5L value set , given its relevance to policy [ 7 ] . In 2017 , NICE released a ‘ position statement ’ [ 8 ] stating that : The 3L value set continues to be used for reference-case analyses . Where 5L data have been collected , reference-case analyses should calculate utilities by mapping the 5L descriptive system data onto the 3L value set , using the van Hout et al. [ 9 ] mapping function . NICE supports sponsors of prospect i ve clinical studies continuing to use the 5L to collect data on quality of life . A further position statement is planned for August 2018 , to be informed by evidence from various studies underway . These include studies commissioned by the English Department of Health to investigate the implication s for past NICE technology appraisal s had the 5L been used , and to collect 3L and 5L data in parallel to further improve functions for mapping from one to the other . Other studies , funded by the EuroQol Group , are also underway , investigating various aspects of the relationship between the 3L and 5L across disease areas . The 3L and its UK value set has occupied a special place in NICE ’s technology appraisal process since its inception , therefore any transition will inevitably pose challenges ; for example , reconciling potential inconsistencies between past and future decisions . Given that evidence will continue to be su bmi tted using both the 3L and 5L for years to come , if both value sets are able to be used , there is a risk of inconsistency between decisions being made in the future . HTA in other countries may also face similar issues . Given the difficulties with any transition away from the 3L , is there a case for NICE to adopt the 5L as its preferred instrument ? Papers in this issue of Pharmacoeconomics , which are cited in this commentary , address that question by investigating comparative performance of the 3L and 5L BACKGROUND Acupuncture is widely used by patients with chronic pain although there is little evidence of its effectiveness . We investigated the efficacy of acupuncture compared with minimal acupuncture and with no acupuncture in patients with osteoarthritis of the knee . METHODS Patients with chronic osteoarthritis of the knee ( Kellgren grade < or = 2 ) were r and omly assigned to acupuncture ( n=150 ) , minimal acupuncture ( superficial needling at non-acupuncture points ; n=76 ) , or a waiting list control ( n=74 ) . Specialised physicians , in 28 outpatient centres , administered acupuncture and minimal acupuncture in 12 sessions over 8 weeks . Patients completed st and ard question naires at baseline and after 8 weeks , 26 weeks , and 52 weeks . The primary outcome was the Western Ontario and McMaster Universities Osteoarthritis ( WOMAC ) index at the end of week 8 ( adjusted for baseline score ) . All main analyses were by intention to treat . RESULTS 294 patients were enrolled from March 6 , 2002 , to January 17 , 2003 ; eight patients were lost to follow-up after r and omisation , but were included in the final analysis . The mean baseline-adjusted WOMAC index at week 8 was 26.9 ( SE 1.4 ) in the acupuncture group , 35.8 ( 1.9 ) in the minimal acupuncture group , and 49.6 ( 2.0 ) in the waiting list group ( treatment difference acupuncture vs minimal acupuncture -8.8 , [ 95 % CI -13.5 to -4.2 ] , p=0.0002 ; acupuncture vs waiting list -22.7 [ -27.5 to -17.9 ] , p<0.0001 ) . After 52 weeks the difference between the acupuncture and minimal acupuncture groups was no longer significant ( p=0.08 ) . INTERPRETATION After 8 weeks of treatment , pain and joint function are improved more with acupuncture than with minimal acupuncture or no acupuncture in patients with osteoarthritis of the knee . However , this benefit decreases over time OBJECTIVE The Arthritis , Diet , and Activity Promotion Trial ( ADAPT ) was a r and omized , single-blind clinical trial lasting 18 months that was design ed to determine whether long-term exercise and dietary weight loss are more effective , either separately or in combination , than usual care in improving physical function , pain , and mobility in older overweight and obese adults with knee osteoarthritis ( OA ) . METHODS Three hundred sixteen community-dwelling overweight and obese adults ages 60 years and older , with a body mass index of > or = 28 kg/m(2 ) , knee pain , radiographic evidence of knee OA , and self-reported physical disability , were r and omized into healthy lifestyle ( control ) , diet only , exercise only , and diet plus exercise groups . The primary outcome was self-reported physical function as measured with the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . Secondary outcomes included weight loss , 6-minute walk distance , stair-climb time , WOMAC pain and stiffness scores , and joint space width . RESULTS Of the 316 r and omized participants , 252 ( 80 % ) completed the study . Adherence was as follows : for healthy lifestyle , 73 % ; for diet only , 72 % ; for exercise only , 60 % ; and for diet plus exercise , 64 % . In the diet plus exercise group , significant improvements in self-reported physical function ( P < 0.05 ) , 6-minute walk distance ( P < 0.05 ) , stair-climb time ( P < 0.05 ) , and knee pain ( P < 0.05 ) relative to the healthy lifestyle group were observed . In the exercise group , a significant improvement in the 6-minute walk distance ( P < 0.05 ) was observed . The diet-only group was not significantly different from the healthy lifestyle group for any of the functional or mobility measures . The weight-loss groups lost significantly ( P < 0.05 ) more body weight ( for diet , 4.9 % ; for diet plus exercise , 5.7 % ) than did the healthy lifestyle group ( 1.2 % ) . Finally , changes in joint space width were not different between the groups . CONCLUSION The combination of modest weight loss plus moderate exercise provides better overall improvements in self-reported measures of function and pain and in performance measures of mobility in older overweight and obese adults with knee OA compared with either intervention alone Background Few population -based studies have examined the prevalence of foot pain in the general community . The aims of this study were therefore to determine the prevalence , correlates and impact of foot pain in a population -based sample of people aged 18 years and over living in the northwest region of Adelaide , South Australia . Methods The North West Adelaide Health Study is a representative longitudinal cohort study of n = 4,060 people r and omly selected and recruited by telephone interview . The second stage of data collection on this cohort was undertaken between mid 2004 and early 2006 . In this phase , information regarding the prevalence of musculoskeletal conditions was included . Overall , n = 3,206 participants returned to the clinic during the second visit , and as part of the assessment were asked to report whether they had pain , aching or stiffness on most days in either of their feet . Data were also collected on body mass index ( BMI ) ; major medical conditions ; other joint symptoms and health-related quality of life ( the Medical Outcomes Study Short Form 36 [ SF-36 ] ) . Results Overall , 17.4 % ( 95 % confidence interval 16.2 – 18.8 ) of participants indicated that they had foot pain , aching or stiffness in either of their feet . Females , those aged 50 years and over , classified as obese and who reported knee , hip and back pain were all significantly more likely to report foot pain . Respondents with foot pain scored lower on all domains of the SF-36 after adjustment for age , sex and BMI . Conclusion Foot pain affects nearly one in five of people in the community , is associated with increased age , female sex , obesity and pain in other body regions , and has a significant detrimental impact on health-related quality of life OBJECTIVE To evaluate the clinical effectiveness of manual physiotherapy and /or exercise physiotherapy in addition to usual care for patients with osteoarthritis ( OA ) of the hip or knee . DESIGN In this 2 × 2 factorial r and omized controlled trial , 206 adults ( mean age 66 years ) who met the American College of Rheumatology criteria for hip or knee OA were r and omly allocated to receive manual physiotherapy ( n = 54 ) , multi-modal exercise physiotherapy ( n = 51 ) , combined exercise and manual physiotherapy ( n = 50 ) , or no trial physiotherapy ( n = 51 ) . The primary outcome was change in the Western Ontario and McMaster osteoarthritis index ( WOMAC ) after 1 year . Secondary outcomes included physical performance tests . Outcome assessors were blinded to group allocation . RESULTS Of 206 participants recruited , 193 ( 93.2 % ) were retained at follow-up . Mean ( SD ) baseline WOMAC score was 100.8 ( 53.8 ) on a scale of 0 - 240 . Intention to treat analysis showed adjusted reductions in WOMAC scores at 1 year compared with the usual care group of 28.5 ( 95 % confidence interval ( CI ) 9.2 - 47.8 ) for usual care plus manual therapy , 16.4 ( -3.2 to 35.9 ) for usual care plus exercise therapy , and 14.5 ( -5.2 to 34.1 ) for usual care plus combined exercise therapy and manual therapy . There was an antagonistic interaction between exercise therapy and manual therapy ( P = 0.027 ) . Physical performance test outcomes favoured the exercise therapy group . CONCLUSIONS Manual physiotherapy provided benefits over usual care , that were sustained to 1 year . Exercise physiotherapy also provided physical performance benefits over usual care . There was no added benefit from a combination of the two therapies . TRIAL REGISTRATION NUMBER Australian New Zeal and Clinical Trials Registry ACTRN12608000130369 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 PURPOSE The purpose of this study was to compare the cost-effectiveness of dietary and exercise interventions in overweight or obese elderly patients with knee osteoarthritis ( OA ) enrolled in the Arthritis , Diet , and Physical Activity Promotion Trial ( ADAPT ) . METHODS ADAPT was a single-blinded , controlled trial of 316 adults with knee OA , r and omized to one of four groups : Healthy Lifestyle Control group , Diet group , Exercise group , or Exercise and Diet group . A cost analysis was performed from a payer perspective , incorporating those costs and benefits that would be realized by a managed care organization interested in maintaining the health and satisfaction of its enrollees while reducing unnecessary utilization of health care services . RESULTS The Diet intervention was most cost-effective for reducing weight , at $ 35 for each percentage point reduction in baseline body weight . The Exercise intervention was most cost-effective for improving mobility , costing $ 10 for each percentage point improvement in a 6-min walking distance and $ 9 for each percentage point improvement in the timed stair climbing task . The Exercise and Diet intervention was most cost-effective for improving self-reported function and symptoms of arthritis , costing $ 24 for each percentage point improvement in subjective function , $ 20 for each percentage point improvement in self-reported pain , and $ 56 for each percentage point improvement in self-reported stiffness . CONCLUSIONS The Exercise and Diet intervention consistently yielded the greatest improvements in weight , physical performance , and symptoms of knee OA . However , it was also the most expensive and was the most cost-effective approach only for the subjective outcomes of knee OA ( self-reported function , pain , and stiffness ) . Perceived function and symptoms of knee OA are likely to be stronger drivers of downstream health service utilization than weight , or objective performance measures and may be the most cost-effective in the long term Background The delivery of acupuncture alongside mainstream interventions and the cost-effectiveness of “ alternative ” treatments remain areas of controversy . Objective The aim of this study was to assess the cost-utility of adding acupuncture to a course of advice and exercise delivered by UK National Health Service ( NHS ) physical therapists to people with osteoarthritis of the knee . Design A cost-utility analysis was performed alongside a r and omized controlled trial . Methods A total of 352 adults ( aged 50 years or older ) were r and omly assigned to receive 1 of 3 interventions . The primary analysis focused on participants receiving advice and exercise ( AE ) or advice and exercise plus true acupuncture ( AE+TA ) . A secondary analysis considered participants receiving advice and exercise plus nonpenetrating acupuncture ( AE+NPA ) . The main outcome measures were quality -adjusted life years ( QALYs ) , measured by the EQ-5D , and UK NHS costs . Results were expressed as the incremental cost per QALY gained over 12 months . Sensitivity analyses included a broader cost perspective to incorporate private out-of-pocket costs . Results NHS costs were higher for AE+TA ( £ 314 [ British pounds sterling ] ) than for AE alone ( £ 229 ) , and the difference in mean QALYs favored AE+TA ( mean difference=0.022 ) . The base-case cost per QALY gained was £ 3,889 ; this value was associated with a 77 % probability that AE+TA would be more cost-effective than AE at a threshold of £ 20,000 per QALY . Cost-utility data for AE+NPA provided cost-effectiveness estimates similar to those for AE+TA . Limitations As with all trial-based economic evaluations , caution should be exercised when generalizing results beyond the study perspectives . Conclusions A package of AE+TA delivered by NHS physical therapists provided a cost-effective use of health care re sources despite an associated increase in costs . However , the economic benefits could not be attributed to the penetrating nature of conventional acupuncture ; therefore , further research regarding the mechanisms of acupuncture is needed . An analysis of alternative cost perspectives suggested that the results are generalizable to other health care setting The objective of this prospect i ve parallel r and omized single-blind study was to assess that a cycle of mud-bath therapy ( MBT ) provides any benefits over usual treatment in patients with bilateral knee osteoarthritis ( OA ) . Patients with symptomatic primary bilateral knee OA , according to ACR criteria , were included in the study and r and omized to one of two groups : one group received a cycle of MBT at spa center of Chianciano Terme ( Italy ) in addition to the usual treatment , and one group continued their regular care routine alone . Clinical assessment s were performed 7 days before enrollment ( screening visit ) , at the time of enrollment ( basal time ) , after 2 weeks , and after 3 , 6 , 9 , and 12 months after the beginning of the study . All assessment s were conducted by two research ers blinded to treatment allocation . The primary efficacy outcomes were the global pain score evaluated by Visual Analog Scale ( VAS ) and the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) subscore for physical function ( W-TPFS ) . Of the 235 patients screened , 103 met the inclusion criteria : 53 patients were included in the MBT group and 50 in the control group . In the group of patients treated with MBT , we observed a statistically significant ( p < 0.001 ) reduction of VAS and W-TPFS score at the end of the treatment ; this improvement was significant ( p < 0.05 ) also at 3 months of follow-up . The control group did not show significant differences between baseline time and all other times . The differences between one group were significant for both primary parameters already from the 15th day and persisted up to the 9th month . This beneficial effect was confirmed by the significant reduction of symptomatic drug consumption . Tolerability of MBT seemed to be good , with light and transitory side effects . Our results confirm that a cycle of MBT added to usual treatment provides a beneficial effect on the painful symptoms and functional capacities in patients with knee OA that lasts over time . Mud-bath therapy can represent a useful backup to pharmacologic treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments OBJECTIVE To assess the cost effectiveness of a 2-year home exercise program for the treatment of knee pain . METHODS A total of 759 adults aged > or = 45 years were r and omized to receive exercise therapy , monthly telephone contact , exercise therapy and telephone contact , or no intervention . Efficacy was measured using self-reported knee pain at 2 years . Costs to both the National Health Service and to the patient were included . RESULTS Exercise therapy was associated with higher costs and better effectiveness . Direct costs for the interventions were pound 112 for the exercise program and pound 61 for the monthly telephone support . Participants allocated to receive exercise therapy were significantly more likely to incur higher medical costs than those in the no-exercise groups ( mean difference pound 225 ; 95 % confidence interval pound 218 , pound 232 ; P < 0.001 ) . CONCLUSION Exercise therapy is associated with improvements in knee pain , but the cost of delivering the exercise program is unlikely to be offset by any reduction in medical re source use To assess quality of life ( QoL ) , costs , and cost-effectiveness of acupuncture treatment plus routine care versus routine care alone in osteoarthritis patients , a r and omised , controlled trial was conducted in 255 general practice s in Germany . Four hundred and eighty-nine patients with chronic pain due to osteoarthritis of the knee or hip were included to evaluated QoL and costs at baseline and after 3 months using health insurance funds data and st and ardized question naires . Patients receiving acupuncture had an improved QoL associated with significantly higher costs over the 3 months treatment period compared to routine care alone ( mean cost-difference : € 469.50 [ 95%CI € 135.80–€803.19 ] ) . This increase in costs was primarily due to the costs of acupuncture . The overall ICER was € 17,845 per QALY gained . The degree of cost-effectiveness was influenced by gender , with female patients achieving a better cost-effectiveness ratio than men . In conclusion , acupuncture was a cost-effective treatment strategy in patients with chronic osteoarthritis pain OBJECTIVES The aim of the study was to determine the effectiveness of new , individually fitted sports shoes against overuse injuries to the lower limb among newspaper carriers . METHODS Patients ( N = 176 ) with lower-limb overuse injuries were r and omly assigned to use new , individually adjusted footwear with good shock absorbing properties ( test group = 86 ) or the subjects ' own , used footwear ( control group = 90 ) . The main outcome measurements were lower-limb pain intensity during walking , as rated on a visual analogue scale ( 0 - 100 ) , number of painful days , subjective assessment of global improvement , foot fatigue , number of hyperkeratotic skin lesions and diagnosed overuse injuries , and costs of foot care as compared between the treatment groups . RESULTS At the 6-month follow-up there was a difference in favor of the test group with respect to lower-limb pain intensity and number of painful days , when compared with the control group . At 1 year , 53 % and 33 % of the test and control groups , respectively , thought they were better than at the time of the baseline examination ( number needed to treat being 5 between the test and control groups ) . The test subjects had less foot fatigue and fewer hyperkeratotic skin lesions . There was no difference in the number of diagnosed overuse injuries between the groups . During the year of follow-up , the all-inclusive mean costs of foot care were USD 70 and USD 158 in the test and control groups , respectively . CONCLUSIONS Individually adjusted shock-absorbing shoes offer slight health benefits for lower-limb overuse injuries . Proper shoes may decrease the need to use health care re sources Background The need for cost effectiveness analyses in r and omized controlled trials that compare treatment options is increasing . The selection of the optimal utility measure is important , and a central question is whether the two most commonly used indexes - the EuroQuol 5D ( EQ5D ) and the Short Form 6D ( SF6D ) – can be used interchangeably . The aim of the present study was to compare change scores of the EQ5D and SF6D utility indexes in terms of some important measurement properties . The psychometric properties of the two utility indexes were compared to a disease-specific instrument , the Oswestry Disability Index ( ODI ) , in the setting of a r and omized controlled trial for degenerative disc disease . Methods In a r and omized controlled multicentre trial , 172 patients who had experienced low back pain for an average of 6 years were r and omized to either treatment with an intensive back rehabilitation program or surgery to insert disc prostheses . Patients filled out the ODI , EQ5D , and SF-36 at baseline and two-year follow up . The utility indexes was compared with respect to measurement error , structural validity , criterion validity , responsiveness , and interpretability according to the COSMIN taxonomy . Results At follow up , 113 patients had change score values for all three instruments . The SF6D had better similarity with the disease-specific instrument ( ODI ) regarding sensitivity , specificity , and responsiveness . Measurement error was lower for the SF6D ( 0.056 ) compared to the EQ5D ( 0.155 ) . The minimal important change score value was 0.031 for SF6D and 0.173 for EQ5D . The minimal detectable change score value at a 95 % confidence level were 0.157 for SF6D and 0.429 for EQ5D , and the difference in mean change score values ( SD ) between them was 0.23 ( 0.29 ) and so exceeded the clinical significant change score value for both instruments . Analysis of psychometric properties indicated that the indexes are unidimensional when considered separately , but that they do not exactly measure the same underlying construct . Conclusions This study indicates that the difference in important measurement properties between EQ5D and SF6D is too large to consider them interchangeable . Since the similarity with the “ gold st and ard ” ( the disease-specific instrument ) was quite different , this could indicate that the choice of index should be determined by the diagnosis Objective To assess the cost effectiveness of a self management programme plus education booklet for arthritis in primary care . Design Cost effectiveness and cost utility analysis from health and social care and societal perspectives alongside a r and omised controlled trial . Setting 74 general practice s in the United Kingdom . Participants 812 patients aged 50 or more with osteoarthritis of the hips or knees , or both , and pain or disability , or both . Interventions R and omisation to either six sessions of an arthritis self management programme plus an education booklet ( intervention group ) or the education booklet alone ( st and ard care control group ) . Main outcome measures Total health and social care costs and total societal costs at 12 months ; cost effectiveness ( incremental cost effectiveness ratios and cost effectiveness acceptability curves ) on basis of quality of life ( SF-36 , primary outcome measure ) , EuroQol visual analogue scale , and quality adjusted life years ( QALYs ) . Results At 12 months health and social care costs in the intervention group were £ 101 higher ( 95 % confidence interval £ 3 to £ 176 ) than those in the control group because the additional costs of the arthritis self management programme did not seem to be fully offset by savings elsewhere . There were no significant differences in societal costs ( which were up to 13 times the size of health and social care costs ) or any of the outcomes . From the health and social care perspective the intervention was dominated by the control on the basis of QALYs ( which were non-significantly lower in the intervention group ) and had incremental cost effectiveness ratios between £ 279 and £ 13 473 for the other outcomes . From the societal perspective the intervention seemed superior to the control owing to non-significantly lower costs and non-significantly better outcomes on all measures except QALYs . Probabilities of the arthritis self management programme ’s cost effectiveness ranged between 12 % and 97 % ( for thresholds ranging £ 0 to £ 1000 ) based on one point improvements in SF-36 outcomes , but the clinical significance of this is debatable . Probabilities of cost effectiveness on the basis of the visual analogue scale and QALYs were low . Conclusions Cost effectiveness of an arthritis self management programme is not suggested on the basis of current National Institute for Health and Clinical Excellence cost perspectives and QALY thresholds . The probability of cost effectiveness is greater when broader costs and other quality of life outcomes are considered . These results suggest that the cost effectiveness of the Department of Health ’s expert patients programme can not be assumed across all clinical conditions and that further rigorous evaluations for other conditions may be needed . Trial registration Current Controlled Trials IS RCT N79115352 Abstract Objectives : To determine whether a home based exercise programme can improve outcomes in patients with knee pain . Design : Pragmatic , factorial r and omised controlled trial of two years ' duration . Setting : Two general practice s in Nottingham . Participants : 786 men and women aged—45 years with self reported knee pain . Interventions : Participants were r and omised to four groups to receive exercise therapy , monthly telephone contact , exercise therapy plus telephone contact , or no intervention . Patients in the no intervention and combined exercise and telephone groups were r and omised to receive or not receive a placebo health food tablet . Main outcome measures : Primary outcome was self reported score for knee pain on the Western Ontario and McMaster universities ( WOMAC ) osteoarthritis index at two years . Secondary outcomes included knee specific physical function and stiffness ( scored on WOMAC index ) , general physical function ( scored on SF-36 question naire ) , psychological outlook ( scored on hospital anxiety and depression scale ) , and isometric muscle strength . Results : 600 ( 76.3 % ) participants completed the study . At 24 months , highly significant reductions in knee pain were apparent for the pooled exercise groups compared with the non-exercise groups ( mean difference -0.82 , 95 % confidence interval -1.3 to -0.3 ) . Similar improvements were observed at 6 , 12 , and 18 months . Regular telephone contact alone did not reduce pain . The reduction in pain was greater the closer patients adhered to the exercise plan . Conclusions : A simple home based exercise programme can significantly reduce knee pain . The lack of improvement in patients who received only telephone contact suggests that improvements are not just due to psychosocial effects because of contact with the therapist Objective Chronic knee pain is a major cause of disability and health care expenditure , but there are concerns about efficacy , cost , and side effects associated with usual primary care . Conservative rehabilitation may offer a safe , effective , affordable alternative . We compared the effectiveness of a rehabilitation program integrating exercise , self-management , and active coping strategies ( Enabling Self-management and Coping with Arthritic Knee Pain through Exercise [ ESCAPE-knee pain ] ) with usual primary care in improving functioning in persons with chronic knee pain . Methods We conducted a single-blind , pragmatic , cluster r and omized controlled trial . Participants age ≥50 years , reporting knee pain for > 6 months , were recruited from 54 inner-city primary care practice s. Primary care practice s were r and omized to continued usual primary care ( i.e. , whatever intervention a participant 's primary care physician deemed appropriate ) , usual primary care plus the rehabilitation program delivered to individual participants , or usual primary care plus the rehabilitation program delivered to groups of 8 participants . The primary outcome was self-reported functioning ( Western Ontario and McMaster Universities Osteoarthritis Index physical functioning [ WOMAC-func ] ) 6 months after completing rehabilitation . Results A total of 418 participants were recruited ; 76 ( 18 % ) withdrew , only 5 ( 1 % ) due to adverse events . Rehabilitated participants had better functioning than participants continuing usual primary care ( −3.33 difference in WOMAC-func score ; 95 % confidence interval [ 95 % CI ] −5.88 , −0.78 ; P = 0.01 ) . Improvements were similar whether participants received individual rehabilitation ( −3.53 ; 95 % CI −6.52 , −0.55 ) or group rehabilitation ( −3.16 ; 95 % CI −6.55 , −0.12 ) . Conclusion ESCAPE-knee pain provides a safe , relatively brief intervention for chronic knee pain that is equally effective whether delivered to individuals or groups of participants OBJECTIVE To determine the effectiveness of a behavioral grade d activity program ( BGA ) compared with usual care ( UC ; exercise therapy and advice ) according to the Dutch guidelines for physiotherapy in patients with osteoarthritis ( OA ) of the hip and /or knee . The BGA intervention is intended to increase activity in the long term and consists of an exercise program with booster sessions , using operant treatment principles . METHODS We conducted a cluster r and omized trial involving 200 patients with hip and /or knee OA . Primary outcome measures were pain ( visual analog scale [ VAS ] and Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] ) , physical function ( WOMAC ) , and patient global assessment , assessed at weeks 0 , 13 , 39 , and 65 . Secondary outcome measures comprised tiredness ( VAS ) , patient-oriented physical function ( McMaster Toronto Arthritis Patient Preference Disability Question naire [ MACTAR ] ) , 5-meter walking time , muscle strength , and range of motion . Data were analyzed according to intent-to-treat principle . RESULTS Both treatments showed short-term and long-term beneficial within-group effects . The mean differences between the 2 groups for pain and functional status were not statistically significant . Significant differences in favor of BGA were found for the MACTAR functional scale and 5-meter walking test at week 65 . CONCLUSION Because both interventions result ed in beneficial long-term effects , the superiority of BGA over UC has not been demonstrated . Therefore , BGA seems to be an acceptable method to treat patients with hip and /or knee OA , with equivalent results compared with UC This paper presents the rationale and design features of the MeTeOR Trial ( Meniscal Tear in Osteoarthritis Research ; Clinical Trials.gov NCT00597012 ) . MeTeOR is an NIH-funded seven-center prospect i ve r and omized controlled trial ( RCT ) design ed to establish the efficacy of arthroscopic partial meniscectomy combined with a st and ardized physical therapy program as compared with a st and ardized physical therapy program alone in patients with a symptomatic meniscal tear in the setting of mild to moderate knee osteoarthritic change ( OA ) . The design and execution of a trial that compares surgery with a nonoperative treatment strategy presents distinctive challenges . The goal of this paper is to provide the clinical rationale for MeTeOR and to highlight salient design features , with particular attention to those that present clinical and method ologic challenges OBJECTIVES To determine the efficacy of community water-based therapy for the management of lower limb osteoarthritis ( OA ) in older patients . DESIGN A pre-experimental matched-control study was used to estimate efficacy of water-based exercise treatment , to check design assumptions and delivery processes . The main study was a r and omised controlled trial of the effectiveness of water-based exercise ( treatment ) compared with usual care ( control ) in older patients with hip and /or knee OA . The latter was accompanied by an economic evaluation comparing societal costs and consequences of the two treatments . SETTING Water exercise was delivered in public swimming pools in the UK . Physical function assessment s were carried out in established laboratory setting s. PARTICIPANTS 106 patients ( 93 women , 13 men ) over the age of 60 years with confirmed hip and /or knee OA took part in the preliminary study . A similar , but larger , group of 312 patients ( 196 women , 116 men ) took part in the main study , r and omised into control ( 159 ) and water exercise ( 153 ) groups . INTERVENTIONS Control group patients received usual care with quarterly semi-structured telephone interview follow-up only . The intervention in the main study lasted for 1 year , with a further follow-up period of 6 months . MAIN OUTCOME MEASURES Pain score on the Western Ontario and McMaster Universities OA index ( WOMAC ) . Additional outcome measures were included to evaluate effects on quality of life , cost-effectiveness and physical function measurements . RESULTS Short-term efficacy of water exercise in the management of lower limb OA was confirmed , with effect sizes ranging from 0.44 [ 95 % confidence interval ( CI ) 0.03 to 0.85 ] on WOMAC pain to 0.76 ( 95 % CI 0.33 to 1.17 ) on WOMAC physical function . Of 153 patients r and omised to treatment , 82 ( 53.5 % ) were estimated to have complied satisfactorily with their treatment at the 1-year point . This had declined to 28 ( 18 % ) by the end of the 6-month follow-up period , during which support for the intervention had been removed and those wishing to continue exercise had to pay their own costs for maintaining their exercise treatment . High levels of co-morbidity were recorded in both groups . Nearly two thirds of all patients had a significant other illness in addition to their OA . Fifty-four control and 53 exercise patients had hospital inpatient episodes during the study period . Water exercise remained effective in the main study but overall effect size was small , on WOMAC pain at 1 year , a reduction of about 10 % in group mean pain score . This had declined , and was non-significant , at 18 months . Mean cost difference estimates showed a saving in the water exercise group of pound123 - -175 per patient per annum and incremental cost-effectiveness ratios ranged from pound3838 to pound5951 per quality -adjusted life-year ( QALY ) . Net reduction in pain was achieved at a net saving of pound135 - -175 per patient per annum and the ceiling valuation of pound580 - -740 per unit of WOMAC pain reduction was favourably low . CONCLUSIONS Group-based exercise in water over 1 year can produce significant reduction in pain and improvement in physical function in older adults with lower limb OA , and may be a useful adjunct in the management of hip and /or knee OA . The water-exercise programme produced a favourable cost -- benefit outcome , using reduction in WOMAC pain as the measure of benefit . Further research is suggested into other similar public health interventions . Investigation is also needed into how general practice can best be supported to facilitate access to participants for research trials in healthcare , as well as an examination of the infrastructure and workforce capacities for physical activity delivery and the potential extent to which healthcare may be supported in this way . More detailed research is required to develop a better underst and ing of the types of exercise that will work for the different biomechanical subtypes of knee and hip OA and investigation is needed on access and environmental issues for physical activity programmes for older people , from both a provider and a participant perspective , the societal costs of the different approaches to the management of OA and longer term trends in outcome measures ( costs and effects ) OBJECTIVE To determine the effects of structured exercise programs on self-reported disability in older adults with knee osteoarthritis . SETTING AND DESIGN A r and omized , single-blind clinical trial lasting 18 months conducted at 2 academic medical centers . PARTICIPANTS A total of 439 community-dwelling adults , aged 60 years or older , with radiographically evident knee osteoarthritis , pain , and self-reported physical disability . INTERVENTIONS An aerobic exercise program , a resistance exercise program , and a health education program . MAIN OUTCOME MEASURES The primary outcome was self-reported disability score ( range , 1 - 5 ) . The secondary outcomes were knee pain score ( range , 1 - 6 ) , performance measures of physical function , x-ray score , aerobic capacity , and knee muscle strength . RESULTS A total of 365 ( 83 % ) participants completed the trial . Overall compliance with the exercise prescription was 68 % in the aerobic training group and 70 % in the resistance training group . Postr and omization , participants in the aerobic exercise group had a 10 % lower adjusted mean ( + /- SE ) score on the physical disability question naire ( 1.71 + /- 0.03 vs 1.90 + /- 0.04 units ; P<.001 ) , a 12 % lower score on the knee pain question naire ( 2.1 + /- 0.05 vs 2.4 + /- 0.05 units ; P=.001 ) , and performed better ( mean [ + /- SE ] ) on the 6-minute walk test ( 1507 + /- 16 vs 1349 + /- 16 ft ; P<.001 ) , mean ( + /-SE ) time to climb and descend stairs ( 12.7 + /- 0.4 vs 13.9 + /- 0.4 seconds ; P=.05 ) , time to lift and carry 10 pounds ( 9.1 + /- 0.2 vs 10.0 + /- 0.1 seconds ; P<.001 ) , and mean ( + /-SE ) time to get in and out of a car ( 8.7 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P<.001 ) than the health education group . The resistance exercise group had an 8 % lower score on the physical disability question naire ( 1.74 + /- 0.04 vs 1.90 + /- 0.03 units ; P=.003 ) , 8 % lower pain score ( 2.2 + /- 0.06 vs 2.4 + /- 0.05 units ; P=.02 ) , greater distance on the 6-minute walk ( 1406 + /- 17 vs 1349 + /- 16 ft ; P=.02 ) , faster times on the lifting and carrying task ( 9.3 + /- 0.1 vs 10.0 + /- 0.16 seconds ; P=.001 ) , and the car task ( 9.0 + /- 0.3 vs 10.6 + /- 0.3 seconds ; P=.003 ) than the health education group . There were no differences in x-ray scores between either exercise group and the health education group . CONCLUSIONS Older disabled persons with osteoarthritis of the knee had modest improvements in measures of disability , physical performance , and pain from participating in either an aerobic or a resistance exercise program . These data suggest that exercise should be prescribed as part of the treatment for knee osteoarthritis Objective To determine whether dietary intervention or knee strengthening exercise , or both , can reduce knee pain and improve knee function in overweight and obese adults in the community . Design Pragmatic factorial r and omised controlled trial . Setting Five general practice s in Nottingham . Participants 389 men and women aged 45 and over with a body mass index ( BMI ) of ≥28.0 and self reported knee pain . Interventions Participants were r and omised to dietary intervention plus quadriceps strengthening exercises ; dietary intervention alone ; quadriceps strengthening exercises alone ; advice leaflet only ( control group ) . Dietary intervention consisted of individualised healthy eating advice that would reduce normal intake by 2.5 MJ ( 600 kcal ) a day . Interventions were delivered at home visits over a two year period . Main outcome measures The primary outcome was severity of knee pain scored with the Western Ontario McMaster ( WOMAC ) osteoarthritis index at 6 , 12 , and 24 months . Secondary outcomes ( all at 24 months ) included WOMAC knee physical function and stiffness scores and selected domains on the SF-36 and the hospital anxiety and depression index . Results 289 ( 74 % ) participants completed the trial . There was a significant reduction in knee pain in the knee exercise groups compared with those in the non-exercise groups at 24 months ( percentage risk difference 11.61 , 95 % confidence interval 1.81 % to 21.41 % ) . The absolute effect size ( 0.25 ) was moderate . The number needed to treat to benefit from a ≥30 % improvement in knee pain at 24 months was 9 ( 5 to 55 ) . In those r and omised to knee exercise improvement in function was evident at 24 months ( mean difference −3.64 , −6.01 to −1.27 ) . The mean difference in weight loss at 24 months in the dietary intervention group compared with no dietary intervention was 2.95 kg ( 1.44 to 4.46 ) ; for exercise versus no exercise the difference was 0.43 kg ( −0.82 to 1.68 ) . This difference in weight loss was not associated with improvement in knee pain or function but was associated with a reduction in depression ( absolute effect size 0.19 ) . Conclusions A home based , self managed programme of simple knee strengthening exercises over a two year period can significantly reduce knee pain and improve knee function in overweight and obese people with knee pain . A moderate sustained weight loss is achievable with dietary intervention and is associated with reduced depression but is without apparent influence on pain or function . Trial registration Current Controlled Trials IS RCT N 93206785 OBJECTIVE To determine the extent to which the cost of an effective self-care intervention for primary care patients with knee osteoarthritis ( OA ) was offset by savings result ing from reduced utilization of ambulatory medical services . METHODS In an attention-controlled clinical trial , 211 patients with knee OA from the general medicine clinic of a municipal hospital were assigned arbitrarily to conditions of self-care education ( group E ) or attention control ( group AC ) . Group E ( n = 105 ) received individualized instruction and followup emphasizing nonpharmacologic management of joint pain . Group AC ( n = 106 ) received a st and ard public education presentation and attention-controlling followup . A comprehensive clinical data base provided data concerning utilization and cost of health services during the following year . RESULTS Only 25 subjects ( 12 % ) were lost to followup . The 94 subjects remaining in group E made 528 primary care visits during the year following intervention , compared with 616 visits by the 92 patients remaining in group AC ( median visits 5 versus 6 , respectively ; P < 0.05 ) . Fewer visits translated directly into reduced clinic costs in group E , relative to controls ( median costs [ 1996 dollars ] $ 229 versus $ 305 , respectively ; P < 0.05 ) . However , self-care education had no significant effects on utilization and costs of outpatient pharmacy , laboratory , or radiology services over the ensuing year . The cost per patient to deliver the self-care intervention was estimated to be $ 58.70 . CONCLUSION Eighty percent of the cost of delivering effective self-care education to the knee OA patients in this study was offset within 1 year by the reduced frequency and costs of primary care visits . For > 50 % of patients receiving the intervention , the savings associated with fewer primary care visits exceeded the cost of self-care education INTRODUCTION Soft tissue injuries of the leg , ankle , or foot are common and often treated by exercise . The purpose of this study was to determine the effectiveness of exercise for the management of soft tissue injuries of the leg , ankle , or foot . METHODS A systematic review of the literature was conducted . We search ed five data bases from 1990 to 2015 . Relevant articles were critically appraised using Scottish Intercollegiate Guidelines Network ( SIGN ) criteria . The evidence from studies with low risk of bias was synthesized using the best- evidence synthesis methodology . RESULTS We screened 7946 articles . We critically appraised ten r and omized trials and six had a low risk of bias . The evidence suggests that for recent lateral ankle sprain : 1 ) rehabilitation exercises initiated immediately post-injury are as effective as a similar program initiated one week post-injury ; and 2 ) supervised progressive exercise plus education/advice and home exercise lead to similar outcomes as education/advice and home exercise . Eccentric exercises may be more effective than an AirHeel brace but less effective than acupuncture for Achilles tendinopathy of more than two months duration . Finally , for plantar heel pain , static stretching of the calf muscles and sham ultrasound lead to similar outcomes , while static plantar fascia stretching provides short-term benefits compared to shockwave therapy . CONCLUSIONS We found little evidence to support the use of early or supervised exercise interventions for lateral ankle sprains . Eccentric exercises may provide short-term benefits over a brace for persistent Achilles tendinopathy and plantar fascia stretching provides short-term benefits for plantar heel pain This study evaluated the clinical effectiveness and cost-effectiveness of two different types of foot orthoses used to treat plantar heel pain . Forty-eight patients were r and omly assigned to receive either a functional or an accommodative orthosis . General ( EuroQol ) and specific ( Foot Health Status Question naire ) health-status measures were used . Data were also collected using economic question naires relating to National Health Service costs for podiatry , other health-service costs , and patient costs . Data were measured at baseline and at 4- and 8-week intervals . Thirty-five patients completed the study . The results demonstrated a significant decrease in foot pain and a significant increase in foot function with the functional foot orthoses over the 8-week trial . The accommodative foot orthoses demonstrated a significant reduction in foot pain only at 4 weeks . The cost-effectiveness analysis demonstrated that functional orthoses , although initially more expensive , result in a better quality of life . Use of functional orthoses result ed in an increased cost of pound 17.99 ( 32.74 dollars ) per patient , leading to an incremental cost per quality -adjusted life year of pound 1,650 ( 3,003 dollars ) for functional orthoses OBJECTIVE To evaluate a concise program of self-care education delivered by an arthritis nurse specialist as an adjunct to primary care for inner-city patients with knee osteoarthritis ( OA ) . METHODS An attention-controlled clinical trial ; 211 inner-city patients with knee OA were assigned arbitrarily to education ( E ) or attention-control ( AC ) conditions . Group E received an individualized 30 - 60-minute educational intervention that emphasized nonpharmacologic management of joint pain , preservation of function by problem-solving , and practice of principles of joint protection . Brief telephone contacts 1 week and 4 weeks later monitored and reinforced new self-care activities . Group AC viewed a 20-minute st and ardized public education presentation on arthritis and received followup telephone calls ( only to encourage continued participation in the study ) . Outcomes included the Health Assessment Question naire ( HAQ ) Disability and Discomfort Scales , 10-cm visual analog scales measuring knee pain at rest and while walking , and the Quality of Well-Being ( QWB ) scale . Assessment s were made at baseline and at 4-month intervals for 1 year . RESULTS A total of 165 subjects ( 78 % ) completed all assessment s. After control for baseline status , group E had significantly lower scores for disability and resting knee pain throughout the year of postintervention followup ( P < 0.05 for both ) . Effects were somewhat discordant . By 12 months , functional benefits had begun to wane , while the effect on resting knee pain had grown . The overall effects of education on walking knee pain , overall joint pain ( by HAQ ) , and general health status ( by QWB ) were not significant . CONCLUSION Self-care education for inner-city patients with knee OA , delivered as an adjunct to primary care , was found to result in notable preservation of function and control of resting knee pain . The magnitude of the observed effects compares well with those of more labor-intensive and time-consuming intervention models . However , more sustained preservation of function and consistent effects on pain may require prolonged , more proactive followup , either by the patient educator or by a trained clinical assistant dedicated to the task of supporting self-care by patients with knee OA Objective To estimate the cost effectiveness of four different lifestyle interventions for knee pain . Design Cost utility analysis of r and omised controlled trial . Setting Five general practice s in the United Kingdom . Participants 389 adults aged ≥45 with self reported knee pain and body mass index ( BMI ) ≥28 . Interventions Dietary intervention plus quadriceps strengthening exercises , dietary intervention , quadriceps strengthening exercises , and leaflet provision . Participants received home visits over a two year period . Main outcome measure Incremental cost per quality adjusted life year ( QALY ) gained over two years from a health service perspective . Results Advice leaflet was associated with a mean change in cost of −£31 , and a mean QALY gain of 0.085 . Both strengthening exercises and dietary intervention were more effective ( 0.090 and 0.133 mean QALY gain , respectively ) but were not cost effective . Dietary intervention plus strengthening exercises had a mean cost of £ 647 and a mean QALY gain of 0.147 and was estimated to have an incremental cost of £ 10 469 per QALY gain ( relative to leaflet provision ) , and a 23.1 % probability of being cost effective at a £ 20 000/QALY threshold . Conclusion Dietary intervention plus strengthening exercises was estimated to be cost effective for individuals with knee pain , but with a large level of uncertainty . Trial registration IS RCT N93206785 Abstract Objective To evaluate clinical effectiveness of a self management programme for arthritis in patients in primary care with osteoarthritis . Design R and omised controlled trial . Setting 74 general practice s in the United Kingdom . Participants 812 patients aged 50 and over with osteoarthritis of hips or knees ( or both ) and pain or disability ( or both ) . Intervention Participants were r and omised to six sessions of self management of arthritis and an education booklet ( intervention group ) or the education booklet alone ( control group ) . Main outcome measures Primary outcome was quality of life , as assessed by the short form health survey ( SF-36 ) . Several other physical and psychosocial secondary outcomes were assessed . Data were collected at baseline , four months , and 12 months . Results Response rates were 80 % and 76 % at four and 12 months . The two groups showed significant differences at 12 months on the anxiety subscore of the hospital anxiety and depression scale ( mean difference −0.62 , 95 % confidence interval −1.08 to −0.16 ) , arthritis self efficacy scale for pain ( 0.98 , 0.07 to 1.89 ) , and self efficacy for other aspects of management ( 1.58 , 0.25 to 2.90 ) . Results were similar for intention to treat and per protocol analyses . No significant difference was seen in number of visits to the general practitioner at 12 months . Conclusions The self management of arthritis programme reduced anxiety and improved participants ' perceived self efficacy to manage symptoms , but it had no significant effect on pain , physical functioning , or contact with primary care . Trial registration Current Controlled Trials IS RCT N79115352 [ controlled-trials.com ] OBJECTIVE To investigate the effectiveness of acupuncture in addition to routine care , compared with routine care alone , in the treatment of patients with chronic pain due to osteoarthritis ( OA ) of the knee or hip . METHODS In a r and omized , controlled trial , patients with chronic pain due to OA of the knee or hip were r and omly allocated to undergo up to 15 sessions of acupuncture in a 3-month period or to a control group receiving no acupuncture . Another group of patients who did not consent to r and omization underwent acupuncture treatment . All patients were allowed to receive usual medical care in addition to the study treatment . Clinical OA severity ( Western Ontario and McMaster Universities Osteoarthritis Index [ WOMAC ] ) and health-related quality of life ( Short Form 36 ) were assessed at baseline and after 3 months and 6 months . RESULTS Of 3,633 patients ( mean + /- SD age 61.8 + /- 10.8 years ; 61 % female ) , 357 were r and omized to the acupuncture group and 355 to the control group , and 2,921 were included in the nonr and omized acupuncture group . At 3 months , the WOMAC had improved by a mean + /- SEM of 17.6 + /- 1.0 in the acupuncture group and 0.9 + /- 1.0 in the control group ( 3-month scores 30.5 + /- 1.0 and 47.3 + /- 1.0 , respectively [ difference in improvement 16.7 + /- 1.4 ; P < 0.001 ] ) . Similarly , quality of life improvements were more pronounced in the acupuncture group versus the control group ( P < 0.001 ) . Treatment success was maintained through 6 months . The changes in outcome in nonr and omized patients were comparable with those in r and omized patients who received acupuncture . CONCLUSION These results indicate that acupuncture plus routine care is associated with marked clinical improvement in patients with chronic OA-associated pain of the knee or hip Objective : To evaluate whether exercise treatment based on behavioural grade d activity comprising booster sessions is a cost-effective treatment for patients with osteoarthritis of the hip and /or knee compared with usual care . Methods : An economic evaluation from a societal perspective was carried out alongside a r and omised trial involving 200 patients with osteoarthritis of the hip and /or knee . Outcome measures were pain , physical functioning , self-perceived change and quality of life , assessed at baseline , 13 , 39 and 65 weeks . Costs were measured using cost diaries for the entire follow-up period of 65 weeks . Cost and effect differences were estimated using multilevel analysis . Uncertainty around the cost-effectiveness ratios was estimated by bootstrapping and graphically represented on cost-effectiveness planes . Results : 97 patients received behavioural grade d activity , and 103 patients received usual care . At 65 weeks , no differences were found between the two groups in improvement with respect to baseline on any of the outcome measures . The mean ( 95 % confidence interval ) difference in total costs between the groups was −€773 ( −€2360 to € 772)—that is , behavioural grade d activity result ed in less cost but this difference was non-significant . As effect differences were small , a large incremental cost-effectiveness ratio of € 51 385 per quality adjusted life year was found for grade d activity versus usual care . Conclusions : This study provides no evidence that behavioural grade d activity is either more effective or less costly than usual care . Yielding similar results to usual care , behavioural grade d activity seems an acceptable method for treating patients with osteoarthritis of the hip and /or knee PURPOSE The purpose of this study was to determine , in a r and omized clinical trial of 439 individuals with knee osteoarthritis , the incremental cost-effectiveness of aerobic versus weight resistance training , compared with an education control intervention . METHODS Cost estimates of the intervention were based upon the cost of purchasing from the community similar services to provide exercise or health education . Effect at 18 months was measured using several variables , including : self-reported disability score , 6-min walking distance , stair climb , lifting and carrying task , car task , and measures of pain frequency and pain intensity on ambulation and transfer . RESULTS The total cost of the educational intervention was $ 343.98 per participant . The aerobic exercise intervention cost $ 323.55 per participant , and the resistance training intervention cost $ 325.20 per participant . On all but two of the outcome variables , the incremental savings per incremental effect for the resistance exercise group was greater than for the aerobic exercise group . CONCLUSION The data obtained from this study suggest that , compared with an education control , resistance training for seniors with knee osteoarthritis is more economically efficient than aerobic exercise in improving physical function . However , the magnitude of the difference in efficiency between the two approaches is small Objective To investigate the benefit of adding acupuncture to a course of advice and exercise delivered by physiotherapists for pain reduction in patients with osteoarthritis of the knee . Design Multicentre , r and omised controlled trial . Setting 37 physiotherapy centres accepting primary care patients referred from general practitioners in the Midl and s , United Kingdom . Participants 352 adults aged 50 or more with a clinical diagnosis of knee osteoarthritis . Interventions Advice and exercise ( n=116 ) , advice and exercise plus true acupuncture ( n=117 ) , and advice and exercise plus non-penetrating acupuncture ( n=119 ) . Main outcome measures The primary outcome was change in scores on the Western Ontario and McMaster Universities osteoarthritis index pain subscale at six months . Secondary outcomes included function , pain intensity , and unpleasantness of pain at two weeks , six weeks , six months , and 12 months . Results Follow-up rate at six months was 94 % . The mean ( SD ) baseline pain score was 9.2 ( 3.8 ) . At six months mean reductions in pain were 2.28 ( 3.8 ) for advice and exercise , 2.32 ( 3.6 ) for advice and exercise plus true acupuncture , and 2.53 ( 4.2 ) for advice and exercise plus non-penetrating acupuncture . Mean differences in change scores between advice and exercise alone and each acupuncture group were 0.08 ( 95 % confidence interval −1.0 to 0.9 ) for advice and exercise plus true acupuncture and 0.25 ( −0.8 to 1.3 ) for advice and exercise plus non-penetrating acupuncture . Similar non-significant differences were seen at other follow-up points . Compared with advice and exercise alone there were small , statistically significant improvements in pain intensity and unpleasantness at two and six weeks for true acupuncture and at all follow-up points for non-penetrating acupuncture . Conclusion The addition of acupuncture to a course of advice and exercise for osteoarthritis of the knee delivered by physiotherapists provided no additional improvement in pain scores . Small benefits in pain intensity and unpleasantness were observed in both acupuncture groups , making it unlikely that this was due to acupuncture needling effects . Trial registration Current Controlled Trials IS RCT N88597683 BACKGROUND Chronic knee pain is a major cause of disability in the elderly . Management guidelines recommend exercise and self-management interventions as effective treatments . The authors previously described a rehabilitation programme integrating exercise and self-management [ Enabling Self-management and Coping with Arthritic knee Pain through Exercise ( ESCAPE-knee pain ) ] that produced short-term improvements in pain and physical function , but sustaining these improvements is difficult . Moreover , the programme is untried in clinical environments , where it would ultimately be delivered . OBJECTIVES To establish the feasibility of ESCAPE-knee pain and compare its clinical effectiveness and costs with outpatient physiotherapy . DESIGN Pragmatic , r and omised controlled trial . SETTING Outpatient physiotherapy department and community centre . PARTICIPANTS Sixty-four people with chronic knee pain . INTERVENTIONS Outpatient physiotherapy compared with ESCAPE-knee pain . OUTCOMES The primary outcome was physical function assessed using the Western Ontario and McMaster Universities Osteoarthritis Index . Secondary outcomes included pain , objective functional performance , anxiety , depression , exercise-related health beliefs and healthcare utilisation . All outcomes were assessed at baseline and 12 months after completing the interventions ( primary endpoint ) . ANCOVA investigated between-group differences . RESULTS Both groups demonstrated similar improvements in clinical outcomes . Outpatient physiotherapy cost pound 130 per person and the healthcare utilisation costs of participants over 1 year were pound 583 . The ESCAPE-knee pain programme cost pound 64 per person and the healthcare utilisation costs of participants over 1 year were pound 320 . CONCLUSIONS ESCAPE-knee pain can be delivered as a community-based integrated rehabilitation programme for people with chronic knee pain . Both ESCAPE-knee pain and outpatient physiotherapy produced sustained physical and psychosocial benefits , but ESCAPE-knee pain cost less and was more cost-effective BACKGROUND Whether arthroscopic partial meniscectomy for symptomatic patients with a meniscal tear and knee osteoarthritis results in better functional outcomes than nonoperative therapy is uncertain . METHODS We conducted a multicenter , r and omized , controlled trial involving symptomatic patients 45 years of age or older with a meniscal tear and evidence of mild-to-moderate osteoarthritis on imaging . We r and omly assigned 351 patients to surgery and postoperative physical therapy or to a st and ardized physical-therapy regimen ( with the option to cross over to surgery at the discretion of the patient and surgeon ) . The patients were evaluated at 6 and 12 months . The primary outcome was the difference between the groups with respect to the change in the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) physical-function score ( ranging from 0 to 100 , with higher scores indicating more severe symptoms ) 6 months after r and omization . RESULTS In the intention-to-treat analysis , the mean improvement in the WOMAC score after 6 months was 20.9 points ( 95 % confidence interval [ CI ] , 17.9 to 23.9 ) in the surgical group and 18.5 ( 95 % CI , 15.6 to 21.5 ) in the physical-therapy group ( mean difference , 2.4 points ; 95 % CI , -1.8 to 6.5 ) . At 6 months , 51 active participants in the study who were assigned to physical therapy alone ( 30 % ) had undergone surgery , and 9 patients assigned to surgery ( 6 % ) had not undergone surgery . The results at 12 months were similar to those at 6 months . The frequency of adverse events did not differ significantly between the groups . CONCLUSIONS In the intention-to-treat analysis , we did not find significant differences between the study groups in functional improvement 6 months after r and omization ; however , 30 % of the patients who were assigned to physical therapy alone underwent surgery within 6 months . ( Funded by the National Institute of Arthritis and Musculoskeletal and Skin Diseases ; METEOR Clinical Trials.gov number , NCT00597012 . ) OBJECTIVE To evaluate the cost effectiveness of manual physiotherapy , exercise physiotherapy , and a combination of these therapies for patients with osteoarthritis of the hip or knee . METHODS 206 Adults who met the American College of Rheumatology criteria for hip or knee osteoarthritis were included in an economic evaluation from the perspectives of the New Zeal and health system and society alongside a r and omized controlled trial . Re source use was collected using the Osteoarthritis Costs and Consequences Question naire . Quality -adjusted life years ( QALYs ) were calculated using the Short Form 6D . Willingness-to-pay threshold values were based on one to three times New Zeal and 's gross domestic product ( GDP ) per capita of NZ$ 29,149 ( in 2009 ) . RESULTS All three treatment programmes result ed in incremental QALY gains relative to usual care . From the perspective of the New Zeal and health system , exercise therapy was the only treatment to result in an incremental cost utility ratio under one time GDP per capita at NZ$ 26,400 ( -$34,081 to $ 103,899 ) . From the societal perspective manual therapy was cost saving relative to usual care for most scenarios studied . Exercise therapy result ed in incremental cost utility ratios regarded as cost effective but was not cost saving . For most scenarios combined therapy was not as cost effective as the two therapies alone . CONCLUSIONS In this study , exercise therapy and manual therapy were more cost effective than usual care at policy relevant values of willingness-to-pay from both the perspective of the health system and society . Trial registration number Australian New Zeal and Clinical Trials Registry ACTRN12608000130369 Objective : To evaluate the short- and long-term effectiveness of exercise training in relation to pain , function and direct costs to health care systems attributable to hip osteoarthritis . Design : Prospect i ve , two-year r and omized controlled trial . Setting : An outpatient primary health care setting . Subjects : One hundred and twenty men and women aged from 55 to 80 , with radiologically diagnosed hip osteoarthritis with associated clinical symptoms . Interventions : The combined exercise and general practitioner ( GP ) care group received 12 supervised ( once per week ) exercise sessions at the baseline and four additional booster sessions one year later . Both groups received st and ard GP care . Main measures : The WOMAC Osteoarthritis Index , physical functioning score of R AND -36 ( SF-36 ) , the use and health care system costs of doctor visits and physiotherapy associated with hip osteoarthritis , number of total hip replacements , the use of analgesic and non-steroidal anti-inflammatory drugs ( NSAIDs ) , performance-based outcome scores and body mass index ( BMI ) . Results : There were no differences between the groups with respect to WOMAC hip pain , physical functioning score of R AND -36 , performance-based outcome scores or BMI . The effect of the exercise intervention on WOMAC function was statistically significant at 6 months ( mean = −7.5 ; 95 % confidence interval ( CI ) −13.9 to −1.0 ; P = 0.02 ) and 18 months ( mean = −7.9 ; 95 % CI −15.3 to −0.4 ; P = 0.04 ) . There were no statistically significant differences in the total health care system costs between the groups . Conclusion : The mostly home-based exercise training programme provided in this study did not result in reduced hip pain over the two-year follow-up period |
12,145 | 31,173,119 | Conclusions and Relevance Communication interventions are associated with patient decisions regarding do-not-resuscitate code status and better patient knowledge and may thus improve code status discussion | Importance Whether specific communication interventions to discuss code status alter patient decisions regarding do-not-resuscitate code status and knowledge about cardiopulmonary resuscitation ( CPR ) remains unclear .
Objective To conduct a systematic review and meta- analysis regarding the association of communication interventions with patient decisions and knowledge about CPR . | ABSTRACT BACKGROUND Decisions about cardiopulmonary resuscitation ( CPR ) and intubation are a core part of advance care planning , particularly for seriously ill hospitalized patients . However , these discussion s are often avoided . OBJECTIVES We aim ed to examine the impact of a video decision tool for CPR and intubation on patients ’ choices , knowledge , medical orders , and discussion s with providers . DESIGN This was a prospect i ve r and omized trial conducted between 9 March 2011 and 1 June 2013 on the internal medicine services at two hospitals in Boston . PARTICIPANTS One hundred and fifty seriously ill hospitalized patients over the age of 60 with an advanced illness and a prognosis of 1 year or less were included . Mean age was 76 and 51 % were women . INTERVENTIONThree-minute video describing CPR and intubation plus verbal communication of participants ’ preferences to their physicians ( intervention ) ( N = 75 ) or control arm ( usual care ) ( N = 75).MAIN MEASURES The primary outcome was participants ’ preferences for CPR and intubation ( immediately after viewing the video in the intervention arm ) . Secondary outcomes included : orders to withhold CPR/intubation , documented discussion s with providers during hospitalization , and participants ’ knowledge of CPR/ intubation ( five-item test , range 0–5 , higher scores indicate greater knowledge ) . RESULTS Intervention participants ( vs. controls ) were more likely not to want CPR ( 64 % vs. 32 % , p < 0.0001 ) and intubation ( 72 % vs. 43 % , p < 0.0001 ) . Intervention participants ( vs. controls ) were also more likely to have orders to withhold CPR ( 57 % vs. 19 % , p < 0.0001 ) and intubation ( 64 % vs.19 % , p < 0.0001 ) by hospital discharge , documented discussion s about their preferences ( 81 % vs. 43 % , p < 0.0001 ) , and higher mean knowledge scores ( 4.11 vs. 2.45 ; p < 0.0001 ) . CONCLUSIONS Seriously ill patients who viewed a video about CPR and intubation were more likely not to want these treatments , be better informed about their options , have orders to forgo CPR/ intubation , and discuss preferences with providers . Trial registration : Clinical trials.gov NCT01325519 Registry Name : A prospect i ve r and omized trial using video images in advance care planning in seriously ill hospitalized patients Background Previous studies have demonstrated that video of and scripted information about cardiopulmonary resuscitation ( CPR ) can be deployed during clinician – patient end-of-life discussion s. Few studies , however , examine whether video adds to verbal information-sharing . We hypothesized that video augments script-only decision-making . Methods Patients aged > 65 years admitted to hospital wards were r and omized to receive evidence -based information ( “ script ” ) vs. script plus video of simulated CPR and intubation . Patients ’ decisions registered in the hospital record , by hospital discharge were compared for the two groups . Results Fifty script-only intervention patients averaging 77.7 years were compared to 50 script+video patients with a mean age of 74.7 years . Eleven of 50 ( 22 % ) in each group declined CPR ; and an additional three ( script ) vs. four ( script+video ) refused intubation for respiratory failure . There were no differences in sex , self-reported health trajectory , functional limitations , length of stay , or mortality associated with decisions . Conclusion The rate at which verbally informed hospitalized elders opted out of resuscitation was not impacted by adding a video depiction of CPR BACKGROUND : Patient preferences regarding cardiopulmonary resuscitation ( CPR ) are important , especially during hospitalization when a patient 's health is changing . Yet many patients are not adequately informed or involved in the decision‐making process . OBJECTIVES : We examined the effect of an informational video about CPR on hospitalized patients ' code status choices . DESIGN : This was a prospect i ve , r and omized trial conducted at the Minneapolis Veterans Affairs Health Care System in Minnesota . PARTICIPANTS : We enrolled 119 patients , hospitalized on the general medicine service , and at least 65 years old . The majority were men ( 97 % ) with a mean age of 75 . INTERVENTION : A video described code status choices : full code ( CPR and intubation if required ) , do not resuscitate ( DNR ) , and do not resuscitate/do not intubate ( DNR/DNI ) . Participants were r and omized to watch the video ( n = 59 ) or usual care ( n = 60 ) . MEASUREMENTS : The primary outcome was participants ' code status preferences . Secondary outcomes included a question naire design ed to evaluate participants ' trust in their healthcare team and knowledge and perceptions about CPR . RESULTS : Participants who viewed the video were less likely to choose full code ( 37 % ) compared to participants in the usual care group ( 71 % ) and more likely to choose DNR/DNI ( 56 % in the video group vs. 17 % in the control group ) ( P < 0.00001 ) . We did not see a difference in trust in their healthcare team or knowledge and perceptions about CPR as assessed by our question naire . CONCLUSIONS : Hospitalized patients who watched a video about CPR and code status choices were less likely to choose full code and more likely to choose DNR/DNI PURPOSE Decision making regarding cardiopulmonary resuscitation ( CPR ) is challenging . This study examined the effect of a video decision support tool on CPR preferences among patients with advanced cancer . PATIENTS AND METHODS We performed a r and omized controlled trial of 150 patients with advanced cancer from four oncology centers . Participants in the control arm ( n = 80 ) listened to a verbal narrative describing CPR and the likelihood of successful resuscitation . Participants in the intervention arm ( n = 70 ) listened to the identical narrative and viewed a 3-minute video depicting a patient on a ventilator and CPR being performed on a simulated patient . The primary outcome was participants ' preference for or against CPR measured immediately after exposure to either modality . Secondary outcomes were participants ' knowledge of CPR ( score range of 0 to 4 , with higher score indicating more knowledge ) and comfort with video . RESULTS The mean age of participants was 62 years ( st and ard deviation , 11 years ) ; 49 % were women , 44 % were African American or Latino , and 47 % had lung or colon cancer . After the verbal narrative , in the control arm , 38 participants ( 48 % ) wanted CPR , 41 ( 51 % ) wanted no CPR , and one ( 1 % ) was uncertain . In contrast , in the intervention arm , 14 participants ( 20 % ) wanted CPR , 55 ( 79 % ) wanted no CPR , and 1 ( 1 % ) was uncertain ( unadjusted odds ratio , 3.5 ; 95 % CI , 1.7 to 7.2 ; P < .001 ) . Mean knowledge scores were higher in the intervention arm than in the control arm ( 3.3 ± 1.0 v 2.6 ± 1.3 , respectively ; P < .001 ) , and 65 participants ( 93 % ) in the intervention arm were comfortable watching the video . CONCLUSION Participants with advanced cancer who viewed a video of CPR were less likely to opt for CPR than those who listened to a verbal narrative Objective : To determine the relationship of electrocardiographic rhythm during cardiac arrest with survival outcomes . Design : Prospect i ve , observational study . Setting : Total of 411 hospitals in the National Registry of Cardiopulmonary Resuscitation . Patients : Total of 51,919 adult patients with pulseless cardiac arrests from April 1999 to July 2005 . Measurements and Main Results : Registry data collected included first documented rhythm , patient demographics , pre-event data , event data , and survival and neurologic outcome data . Of 51,919 indexed cardiac arrests , first documented pulseless rhythm was ventricular tachycardia ( VT ) in 3810 ( 7 % ) , ventricular fibrillation ( VF ) in 8718 ( 17 % ) , pulseless electrical activity ( PEA ) in 19,262 ( 37 % ) and asystole 20,129 ( 39 % ) . Subsequent VT/VF ( that is , VT or VF occurring during resuscitation for PEA or asystole ) occurred in 5154 ( 27 % ) , with first documented rhythm of PEA and 4988 ( 25 % ) with asystole . Survival to hospital discharge rate was not different between those with first documented VF and VT ( 37 % each , adjusted odds ratio [ OR ] ) 1.08 ; 95 % confidence interval [ CI ] 0.95–1.23 ) . Survival to hospital discharge was slightly more likely after PEA than asystole ( 12 % vs. 11 % , adjusted OR 1.1 ; 95 % CI 1.00–1.18 ) , Survival to discharge was substantially more likely after first documented VT/VF than PEA/asystole ( adjusted OR 1.68 ; 95 % CI 1.55–1.82 ) . Survival to discharge was also more likely after PEA/asystole without subsequent VT/VF compared with PEA/asystole with subsequent VT/VF ( 14 % vs. 7 % for PEA without vs. with subsequent VT/VF ; 12 % vs. 8 % for asystole without vs. with subsequent VT/VF ; adjusted OR 1.60 ; 95 % CI , 1.44–1.80 ) . Conclusions : Survival to hospital discharge was substantially more likely when the first documented rhythm was shockable rather than nonshockable , and slightly more likely after PEA than asystole . Survival to hospital discharge was less likely following PEA/asystole with subsequent VT/VF compared to PEA/asystole without subsequent VT/VF 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 PURPOSE To determine whether the use of a goals -of-care video to supplement a verbal description can improve end-of-life decision making for patients with cancer . METHODS Fifty participants with malignant glioma were r and omly assigned to either a verbal narrative of goals -of-care options at the end of life ( control ) , or a video after the same verbal narrative ( intervention ) in this r and omized controlled trial . The video depicts three levels of medical care : life-prolonging care ( cardiopulmonary resuscitation [ CPR ] , ventilation ) , basic care ( hospitalization , no CPR ) , and comfort care ( symptom relief ) . The primary study outcome was participants ' preferences for end-of-life care . The secondary outcome was participants ' uncertainty regarding decision making ( score range , 3 to 15 ; higher score indicating less uncertainty ) . Participants ' comfort level with the video was also measured . RESULTS Fifty participants were r and omly assigned to either the verbal narrative ( n = 27 ) or video ( n = 23 ) . After the verbal description , 25.9 % of participants preferred life-prolonging care , 51.9 % basic care , and 22.2 % comfort care . In the video arm , no participants preferred life-prolonging care , 4.4 % preferred basic care , 91.3 % preferred comfort care , and 4.4 % were uncertain ( P < .0001 ) . The mean uncertainty score was higher in the video group than in the verbal group ( 13.7 v 11.5 , respectively ; P < .002 ) . In the intervention arm , 82.6 % of participants reported being very comfortable watching the video . CONCLUSION Compared with participants who only heard a verbal description , participants who viewed a goals -of-care video were more likely to prefer comfort care and avoid CPR , and were more certain of their end-of-life decision making . Participants reported feeling comfortable watching the video BACKGROUND Cardiopulmonary resuscitation ( CPR ) is an important advance directive ( AD ) topic in patients with progressive cancer ; however such discussion s are challenging . OBJECTIVE This study investigates whether video educational information about CPR engenders broader advance care planning ( ACP ) discourse . METHODS Patients with progressive pancreas or hepatobiliary cancer were r and omized to an educational CPR video or a similar CPR narrative . The primary end-point was the difference in ACP documentation one month posttest between arms . Secondary end-points included study impressions ; pre- and post-intervention knowledge of and preferences for CPR and mechanical ventilation ; and longitudinal patient outcomes . RESULTS Fifty-six subjects were consented and analyzed . Rates of ACP documentation ( either formal ADs or documented discussion s ) were 40 % in the video arm ( 12/30 ) compared to 15 % in the narrative arm ( 4/26 ) , OR=3.6 [ 95 % CI : 0.9 - 18.0 ] , p=0.07 . Post-intervention knowledge was higher in both arms . Posttest , preferences for CPR had changed in the video arm but not in the narrative arm . Preferences regarding mechanical ventilation did not change in either arm . The majority of subjects in both arms reported the information as helpful and comfortable to discuss , and they recommended it to others . More deaths occurred in the video arm compared to the narrative arm , and more subjects died in hospice setting s in the video arm . CONCLUSIONS This pilot r and omized trial addressing downstream ACP effects of video versus narrative decision tools demonstrated a trend towards more ACP documentation in video subjects . This trend , as well as other video effects , is the subject of ongoing study Objective : To determine if a video depicting cardiopulmonary resuscitation and resuscitation preference options would improve knowledge and decision making among patients and surrogates in the ICU . Design : R and omized , unblinded trial . Setting : Single medical ICU . Patients : Patients and surrogate decision makers in the ICU . Interventions : The usual care group received a st and ard pamphlet about cardiopulmonary resuscitation and cardiopulmonary resuscitation preference options plus routine code status discussion s with clinicians . The video group received usual care plus an 8-minute video that depicted cardiopulmonary resuscitation , showed a simulated hospital code , and explained resuscitation preference options . Measurements and Main Results : One hundred three patients and surrogates were r and omized to usual care . One hundred five patients and surrogates were r and omized to video plus usual care . Median total knowledge scores ( 0–15 points possible for correct answers ) in the video group were 13 compared with 10 in the usual care group , p value of less than 0.0001 . Video group participants had higher rates of underst and ing the purpose of cardiopulmonary resuscitation and resuscitation options and terminology and could correctly name components of cardiopulmonary resuscitation . No statistically significant differences in documented resuscitation preferences following the interventions were found between the two groups , although the trial was underpowered to detect such differences . A majority of participants felt that the video was helpful in cardiopulmonary resuscitation decision making ( 98 % ) and would recommend the video to others ( 99 % ) . Conclusions : A video depicting cardiopulmonary resuscitation and explaining resuscitation preference options was associated with improved knowledge of in-hospital cardiopulmonary resuscitation options and cardiopulmonary resuscitation terminology among patients and surrogate decision makers in the ICU , compared with receiving a pamphlet on cardiopulmonary resuscitation . Patients and surrogates found the video helpful in decision making and would recommend the video to others OBJECTIVE : To describe how medical residents discuss do-not-resuscitate ( DNR ) orders with patients . DESIGN : Prospect i ve observational study . SETTING : Inpatient medical wards of one university tertiary care center , one urban city public hospital , and one Veterans Affairs medical center . PARTICIPANTS : Thirty-one medical residents self-selected 31 of their English-speaking , competent patients , with whom they had DNR discussion s. MEASUREMENTS : Three independent observers rated audiotaped discussion s about DNR orders between the medical residents and their patients . Ratings assessed whether the physicians met st and ard criteria for requesting informed consent ( e.g. , disclosed the nature , benefits , risks , and outcomes ) , addressed the patients ’ values , and attended to the patients ’ emotional concerns . MAIN RESULTS : The physicians often did not provide essential information about cardiopulmonary resuscitation ( CPR ) . While all the physicians mentioned mechanical ventilation , only 55 % mentioned chest compressions and 32 % mentioned intensive care . Only 13 % of the physicians mentioned the patient ’s likelihood of survival after CPR , and no physician used a numerical estimate . The discussion s lasted a median of 10 minutes and were dominated in speaking time by the physicians . The physicians initiated discussion s about the patients ’ personal values and goals of care in 10 % of the cases , and missed opportunities to do so . CONCLUSIONS : Medical ethicists , professional societies , and the public recommend more frequent discussion s about DNR orders . Even when housestaff discuss resuscitation with patients , they may not be accomplishing the goal of increasing patient autonomy . Research and education must focus on improving the quality , as well as the quantity , of these discussion Objective : Predicting outcomes for critically ill patients is an important aspect of discussion s with families in the intensive care unit . Our objective was to evaluate clinical intensive care unit survival predictions and their consequences for mechanically ventilated patients . Design : Prospect i ve cohort study . Setting : Fifteen tertiary care centers . Patients : Consecutive mechanically ventilated patients ≥18 yrs of age with expected intensive care unit stay ≥72 hrs . Interventions : We recorded baseline characteristics at intensive care unit admission . Daily we measured multiple organ dysfunction score ( MODS ) , use of advanced life support , patient preferences for life support , and intensivist and bedside intensive care unit nurse estimated probability of intensive care unit survival . Measurements and Main Results : The 851 patients were aged 61.2 ( ±17.6 , mean ± SD ) yrs with an Acute Physiology and Chronic Health Evaluation ( APACHE ) II score of 21.7 ( ±8.6 ) . Three hundred and four patients ( 35.7 % ) died in the intensive care unit , and 341 ( 40.1 % ) were assessed by a physician at least once to have a < 10 % intensive care unit survival probability . Independent predictors of intensive care unit mortality were baseline APACHE II score ( hazard ratio , 1.16 ; 95 % confidence interval , 1.08–1.24 , for a 5-point increase ) and daily factors such as MODS ( hazard ratio , 2.50 ; 95 % confidence interval , 2.06–3.04 , for a 5-point increase ) , use of inotropes or vasopressors ( hazard ratio , 2.14 ; 95 % confidence interval , 1.66–2.77 ) , dialysis ( hazard ratio , 0.51 ; 95 % confidence interval , 0.35–0.75 ) , patient preference to limit life support ( hazard ratio , 10.22 ; 95 % confidence interval , 7.38–14.16 ) , and physician but not nurse prediction of < 10 % survival . The impact of physician estimates of < 10 % intensive care unit survival was greater for patients without vs. those with preferences to limit life support ( p < .001 ) and for patients with less vs. more severe organ dysfunction ( p < .001 ) . Mechanical ventilation , inotropes or vasopressors , and dialysis were withdrawn more often when physicians predicted < 10 % probability of intensive care unit survival ( all p s < .001 ) . Conclusions : Physician estimates of intensive care unit survival < 10 % are associated with subsequent life support limitation and more powerfully predict intensive care unit mortality than illness severity , evolving or resolving organ dysfunction , and use of inotropes or vasopressors OBJECTIVE To determine the impact of a video on preferences for the primary goal of care . DESIGN , SUBJECTS , AND INTERVENTION Consecutive subjects 65 years of age or older ( n=101 ) admitted to two skilled nursing facilities ( SNFs ) were r and omized to a verbal narrative ( control ) or a video ( intervention ) describing goals -of-care options . Options included : life-prolonging ( i.e. , cardiopulmonary resuscitation ) , limited ( i.e. , hospitalization but no cardiopulmonary resuscitation ) , or comfort care ( i.e. , symptom relief ) . MAIN MEASURES Primary outcome was patients ' preferences for comfort versus other options . Concordance of preferences with documentation in the medical record was also examined . RESULTS Fifty-one subjects were r and omized to the verbal arm and 50 to the video arm . In the verbal arm , preferences were : comfort , n=29 ( 57 % ) ; limited , n=4 ( 8 % ) ; life-prolonging , n=17 ( 33 % ) ; and uncertain , n=1 ( 2 % ) . In the video arm , preferences were : comfort , n=40 ( 80 % ) ; limited , n=4 ( 8 % ) ; and life-prolonging , n=6 ( 12 % ) . R and omization to the video was associated with greater likelihood of opting for comfort ( unadjusted rate ratio , 1.4 ; 95 % confidence interval [ CI ] , 1.1 - 1.9 , p=0.02 ) . Among subjects in the verbal arm who chose comfort , 29 % had a do-not-resuscitate ( DNR ) order ( κ statistic 0.18 ; 95 % CI-0.02 to 0.37 ) ; 33 % of subjects in the video arm choosing comfort had a DNR order ( κ statistic 0.06 ; 95 % CI-0.09 to 0.22 ) . CONCLUSION Subjects admitted to SNFs who viewed a video were more likely than those exposed to a verbal narrative to opt for comfort . Concordance between a preference for comfort and a DNR order was low . These findings suggest a need to improve ascertainment of patients ' preferences . TRIAL REGISTRATION Clinical trials.gov Identifier : NCT01233973 BACKGROUND No national policy requires health care providers to discuss with hospitalized patients whether the latter would want cardiopulmonary resuscitation ( CPR ) or mechanical ventilation ( MV ) in the event of cardiopulmonary failure . OBJECTIVE To determine whether hospitalized patients are willing to discuss end-of-life issues and choose whether to receive CPR and MV . DESIGN Prospect i ve r and omized trial . PARTICIPANTS 297 patients admitted to the medicine service of a 350-bed community teaching hospital . INTERVENTION Patients were r and omized to receive routine care or a scripted intervention , delivered by research physicians , that included detailed information about CPR , MV , and advance directives . MEASUREMENTS Number of patients who welcomed the scripted intervention , number who chose to receive or reject CPR/MV , and number of advance directives created during hospitalization . RESULTS Of the 297 patients studied , 136 were in the intervention group and 161 were in the control group . Baseline characteristics and severity of illness were similar in the 2 groups . Of the 136 patients in the intervention group , 133 ( 98 % ) willingly discussed CPR and mechanical ventilation , and 112 ( 82 % ) found the information useful . One hundred and twenty-five ( 92 % ) clarified their preferences regarding CPR and MV after receiving the intervention ; of the 48 patients who were initially documented as wanting CPR/MV , 3 requested no CPR/MV after the intervention . Of the 87 patients in the intervention group who had no documentation of code status on admission , 5 asked for no CPR/MV . Of the 161 patients in the control group , 55 had documentation of their code status on admission . Of the 106 patients without documentation , 6 were later documented to receive no CPR/MV . Thirteen of the 102 patients who had no advance directive on admission created one after the intervention , whereas only 1 of the 128 patients in the control group did so ( P < .001 ) . CONCLUSIONS Patients are willing to discuss and give informed consent for CPR and mechanical ventilation early in hospitalization . Only a minority drafted advance directives during hospitalization . Larger studies that include patients at other centers are required to determine whether these findings are reproducible and whether this approach is clinical ly feasible OBJECTIVE : To assess the effects of a multimedia educational intervention about advance directives ( ADs ) and cardiopulmonary resuscitation ( CPR ) on the knowledge , attitude and activity toward ADs and life-sustaining treatments of elderly veterans . DESIGN : Prospect i ve r and omized controlled , single blind study of educational interventions . SETTING : General medicine clinic of a university-affiliated Veterans Affairs Medical Center ( VAMC ) . PARTICIPANTS : One hundred seventeen Veterans , 70 years of age or older , deemed able to make medical care decisions . INTERVENTION : The control group ( n=55 ) received a h and out about ADs in use at the VAMC . The experimental group ( n=62 ) received the same h and out , with an additional h and out describing procedural aspects and outcomes of CPR , and they watched a videotape about ADs . MEASUREMENTS AND MAIN RESULTS : Patients ’ attitudes and actions toward ADs , CPR and life-sustaining treatments were recorded before the intervention , after it , and 2 to 4 weeks after the intervention through self-administered question naires . Only 27.8 % of subjects stated that they knew what an AD is in the preintervention question naire . This proportion improved in both the experimental and control ( 87.2 % experimental , 52.5 % control ) subject groups , but stated knowledge of what an AD is was higher in the experimental group ( odds ratio = 6.18 , p<.001 ) and this effect , although diminished , persisted in the follow-up question naire ( OR=3.92 , p=.003 ) . Prior to any intervention , 15 % of subjects correctly estimated the likelihood of survival after CPR . This improved after the intervention in the experimental group ( OR=4.27 , p=.004 ) , but did not persist at follow-up . In the postintervention question naire , few subjects in either group stated that they discussed CPR or ADs with their physician on that day ( OR=0.97 , p = NS ) . CONCLUSION : We developed a convenient means of educating elderly male patients regarding CPR and advance directives that improved short-term knowledge but did not stimulate advance care planning OBJECTIVES To compare patient preferences for end-of-life care with care received at the end of life . DESIGN A r and omized controlled trial was conducted with individuals with congestive heart failure or end-stage renal disease and their surrogates who were r and omized to receive patient-centered advance care planning ( PC-ACP ) or usual care . SETTING Two centers in Wisconsin with associated clinics and dialysis units . PARTICIPANTS Of the 313 individuals and their surrogates who completed entry data , 110 died . INTERVENTION During PC-ACP , the trained facilitator assessed individual and surrogate underst and ing of and experiences with the illness , provided information about disease-specific treatment options and their benefits and burden , assisted in documentation of treatment preferences , and assisted the surrogates in underst and ing the patient 's preferences and the surrogate 's role . MEASUREMENTS Preferences were documented and compared with care received at the end of life according to surrogate interviews or medical charts . RESULTS Patients ( 74 % ) frequently continued to make their own decisions about care to the end . The experimental group had fewer ( 1/62 ) cases in which patients ' wishes about cardiopulmonary resuscitation were not met than in the control group ( 6/48 ) but not significantly so . Significantly more experimental patients withdrew from dialysis than controls . CONCLUSION Patients and their surrogates were generally willing to discuss preferences with a trained facilitator . Most patients received the care they desired at end of life or altered their preferences to be in accord with the care they could receive . A larger sample with surrogate decision-makers is needed to detect significant differences PURPOSE This study tested the efficacy of an intervention on end-of-life decision making for patients with advanced cancer . PATIENTS AND METHODS One hundred twenty patients with metastatic cancer who were no longer being treated with curative intent ( and 87 caregivers ) were r and omly assigned to the intervention ( n = 55 ) or treatment as usual ( n = 65 ) . Primary outcome measures were the proportion of patients with do-not-resuscitate ( DNR ) orders , timing of DNR orders , and place of death . Secondary outcome measures were completed at study enrollment , 3 weeks later , and 3 months later , including patients ' knowledge , mood , and caregiver burden . RESULTS High , but equivalent , rates of DNR orders were observed in both groups . In per- protocol analyses , DNR orders were placed earlier for patients who received the intervention ( median , 27 v 12.5 days ; 95 % CI , 1.1 to 5.9 ; P = .03 ) and they were more likely to avoid a hospital death ( 19 % v 50 % ( 95 % CI , 11 % to 50 % ; P = .004 ) . Differences between the groups over time were evident for estimates of cardiopulmonary rehabilitation ( CPR ) success rates ( P = .01 ) but not knowledge of CPR ( P = .2 ) . There was no evidence that the intervention result ed in more anxious or depressive symptoms . Caregivers experienced less burden in terms of disruption to schedule if the patient received the intervention ( P = .05 ) . CONCLUSION An intervention , consisting of an informational pamphlet and discussion , was associated with earlier placement of DNR orders relative to death and less likelihood of death in hospital . There was no negative impact of the intervention on secondary outcomes , although the sample may have been too small to detect differences Professional societies , citizens ' groups , legislators , and the courts all advocate the use of advance directives to ensure that physicians respect the wishes of patients with regard to treatment at the end of life [ 1 - 5 ] . Physicians are encouraged to discuss these issues in the outpatient setting while patients are healthy and competent . Despite enthusiasm for the use of advance directives , research raises doubts about the ability of advance directives to influence care [ 6 - 12 ] . To underst and why these documents do not work as intended , investigators have examined many facets of the advance directive process , such as the form of the document used , the durability of directives , and the ways in which directives are interpreted [ 6 , 8 , 13 , 14 ] . However , the quality of communication between physicians and patients that leads to the creation of a written directive remains largely an unexplored black box . Studies of advance directive discussion s suggest that physicians do not provide patients with adequate information [ 15 , 16 ] . However , these studies used role playing or st and ardized patients rather than actual patientphysician encounters or lacked generalizability , typically study ing housestaff conversations with in patients about do-not-resuscitate orders [ 16 - 20 ] . We sought to learn how attending physicians in outpatient practice s discuss advance directives with their patients and to observe how closely these discussion s adhere to the informed consent model described in the literature . Methods Participants All primary care internists at five practice sites in Durham , North Carolina , and Pittsburgh , Pennsylvania , were eligible for the study ; only the study investigators were excluded . The sites were two university-based general medicine practice s , two Veterans Affairs general medicine practice s , and one university-based geriatrics practice . Patients were eligible for the study if they were at least 65 years of age or had a serious medical illness ( including cancer ; previous cardiac arrest ; HIV infection ; renal insufficiency [ creatinine concentration > 3 mg/dL ( 250 mol/L ) or long-term dialysis ] ; and chronic obstructive pulmonary disease , congestive heart failure , or cirrhosis severe enough to cause two hospitalizations in the past year ) that made discussion of advance directives relevant . They had to speak English , had to be judged competent by their physician to make medical decisions , and had to have not previously discussed advance directives with their physician . We studied one patient per physician . After physicians indicated a convenient clinic session , we r and omly selected an eligible patient with whom the physician would discuss advance directives in whatever way you think is appropriate for this patient . If physicians felt that such a discussion was inappropriate for that patient , they were asked , in order , about the next eligible patient until a patient was chosen . If no eligible patients were available , we selected another clinic session and repeated the process . We called eligible patients before their visit and requested their consent to participate in a study to learn how doctors communicate with their patients when making decisions about future medical treatments . Data Collection We audiotaped the selected encounters from 1 April 1994 and 30 October 1994 . Physicians completed a self-administered survey that asked about their background and attitudes toward advance directives . We obtained demographic and attitudinal data from patients in face-to-face interviews . The protocol was approved by institutional review boards at the Duke University , Durham Veterans Affairs , and University of Pittsburgh medical centers . Data Analysis Code Book Development All audiotapes were transcribed and coded . We developed the code book through an iterative process [ 21 ] . First , we created general coding categories for all pertinent topics identified in the literature [ 4 , 18 , 22 - 25 ] . Although no clear consensus exists about the ideal content of these discussion s , experts generally recommend a model that reflects the established st and ards of informed consent [ 26 , 27 ] . After explaining the rationale for advance directives , physicians should describe the nature of potential procedures and the risks , benefits , and likely outcomes of and alternatives to these treatments . They should learn whether patients desire treatments under specific scenarios [ 23 , 28 ] . Others also advise physicians to attend to patients ' values and to identify surrogate decision makers [ 16 , 22 , 29 ] . All agree that these discussion s should be conducted in an empathic manner , with sensitivity to patients ' emotional needs [ 16 - 18 , 25 ] . Because this model is not empirically derived , it is only a best approximation for judging discussion quality ; it is not a gold st and ard . On the basis of the model , we coded the ways in which physicians accomplished the following tasks : introducing the topic , describing advance directives , giving rationale s for advance directives , describing pertinent forms , discussing scenarios and treatments , providing medical information , eliciting patient values , and identifying surrogate decision makers . We also developed codes to evaluate the quality of the overall communication process . For each general content area , we formulated a list of specific codes ( Table 1 ) . Table 1 . Major Coding Categories for Discussion s about Advance Directives and Sample s of Specific Codes Next , the research team read the study transcripts to ensure that the coding system captured all relevant issues . Coding categories were adjusted as necessary . After developing a draft of the code book , the research team coded a subset of transcripts to identify problems and formulate coding rules . The final code book contained 70 items spanning 11 topic areas ( Appendix ) . A copy of the complete coding instrument is available from the authors on request . Reliability of the Code Book Two raters independently coded all transcripts . The raters applied as many codes as necessary to the content of each speaker 's turn , which was defined as a segment of uninterrupted speech . scores , used to measure interrater reliability , were greater than 0.40 for 58 of the 70 codes , indicating moderate or better agreement . No codes with scores less than 0.40 were used , with one exception . The code for dire scenario had a score of 0.39 , was present in 91 % of cases , and represented a central concept that emerged repeatedly in qualitative analysis . Disagreements in coding were resolved by consensus between the two coders . Disagreements remained in 11 % of cases and were resolved by the entire research team . The following statement illustrates a case in which the team initially disagreed about whether the scenario was truly dire but , after discussion , decided to apply the code . OK , what if you became ill , for example with something like a stroke . You were in the hospital and you were in a coma , all right . There was very little chance of you ever coming out of that coma . In other words , you could breathe and your heart was still beating , but you could n't really think about things . Statistical Analysis We entered the coded transcripts into the Unix Text Analyzer data base ( University of Pittsburgh Center for Medical Ethics ) , which facilitates indexing and retrieval and is capable of quantitative assessment s of qualitative text ( such as frequency counts on codes ) [ 30 ] . We calculated frequencies for each of the codes and used the chi-square and t-tests to identify variables associated with presence or absence of specific codes . We used st and ard qualitative methods to analyze communication approaches and relevant sections of coded text [ 21 ] . Results Participants Sixty physicians in five practice sites were eligible , and 56 agreed to participate ( 93 % ) ( Table 2 ) . The median age of the physicians was 37 years ( range , 28 to 63 years ) ; 56 % were men , and 93 % were white . They spent a median of 18 hours per week in direct patient care ( range , 2 to 50 hours per week ) and had practice d medicine for a median of 10 years ( range , 3 to 38 years ) . Ninety-five percent of physicians stated that they felt comfortable talking to patients about advance directives , but 61 % rarely discussed advance directives in the outpatient setting . Table 2 . Characteristics of Physicians and Patients Eighty-nine patients were eligible for the study . In 8 cases , physicians refused the discussion because they felt that the patient was emotionally unstable or had had too few previous visits . Fifty-six of the 81 recruited patients ( 69 % ) agreed to participate . Their median age was 72 years ( range , 58 to 88 years ) ; 68 % were men , 84 % were white , and 66 % had less than a 12th- grade education . Twenty-five percent of patients rated their overall health as very good or excellent , 27 % rated it as good , and 48 % rated it as fair or poor . The patients had known their physicians for a median of 1.2 years ( range , 1 month to 12 years ) . The median chance that patients would survive for 5 years , according to their physicians , was 72 % ( range , 9 % to 97 % ) . Participants and persons who refused did not differ significantly in any measured variables , except that more participants were Catholic . Communication Process The median advance directive discussion lasted 5.6 minutes ( range , 0.9 to 15.0 minutes ) . Physicians spoke for a median of 3.9 minutes ( range , 0.6 to 10.9 minutes ) , and patients spoke for the remaining 1.7 minutes ( range , 0.3 to 9.6 minutes ) . When introducing the topic , 93 % of physicians stated why they were discussing advance directives , although 20 % attributed the discussion only to a research project . Usually , the conversation ended without any specific follow-up plan . Forty-three percent of physicians mentioned the possibility of future conversations , 55 % discussed advance directive forms , and 25 % asked patients whether they had questions . Only 16 % of physicians told patients that they could change their mind . In general , physicians were unlikely to attend to Objectives There is wide variability in the discussion of code status by residents among hospitalized patients . The primary objective of this study was to determine the effect of a scripted code status explanation on patient underst and ing of choices pertaining to code status and end-of-life care . Methods This was a single center , r and omized trial in a teaching hospital . Patients were r and omized to a control ( question naire alone ) or intervention arm ( st and ardized explanation+ question naire ) . A composite score was generated based on patient responses to assess comprehension . Results The composite score was 5.27 in the intervention compared to 4.93 in the control arm ( p=0.066 ) . The score was lower in older patients ( p<0.001 ) , patients with multiple comorbidities ( p≤0.001 ) , KATZ score < 6 ( p=0.008 ) , and those living in an assisted living/nursing home ( p=0.005 ) . There were significant differences in patient underst and ing of the ability to receive chest compressions , intravenous fluids , and tube feeds by code status . Conclusion The scripted code status explanation did not significantly impact the composite score . Age , comorbidities , performance status , and type of residence demonstrated a significant association with patient underst and ing of code status choices . Practice implication s St and ardized discussion of code status and training in communication of end-of-life care merit further research Objective Effective communication of simple , clear information to families of intensive care unit ( ICU ) patients is a vital component of quality care . The purpose of this study was to identify factors associated with poor comprehension by family members of the status of ICU patients . Design Prospect i ve study . Setting University-affiliated medical intensive care unit . Patients and Methods A total of 102 patients admitted to an ICU for > 2 days . InterventionThe representatives of 76 patients who were visited by at least one person during their ICU stay were interviewed . Results Mean patient age was 54 ± 17 yrs and mean Simplified Acute Physiology Score II at admission was 40 ± 20 . The representative was the spouse in 47 cases ( 62 % ) . Among representatives , 25 ( 33 % ) were of foreign descent and 12 ( 16 % ) did not speak French . Mean duration of the first meeting with a physician was 10 ± 6 mins . In 34 cases ( 54 % ) , the representative failed to comprehend the diagnosis , prognosis , or treatment of the patient . Factors associated with poor comprehension by representatives included patient-related , family-related , and physician- related factors . Patient-related factors included age < 50 yrs ( p = .03 ) , unemployment ( p = .01 ) , referral from a hematology or oncology ward ( p = .006 ) , admission for acute respiratory failure ( p = .005 ) or coma ( p = .01 ) , and a relatively favorable prognosis ( p = .04 ) . Family-related factors were foreign descent ( p = .007 ) , no knowledge of French ( p = .03 ) , representative not the spouse ( p = .03 ) , and no healthcare professional in the family ( p = .01 ) . Physician-related factors were first meeting with representative < 10 mins ( p = .03 ) and failure to give the representative an information brochure ( p = .02 ) . Moreover , after the first meeting , caregivers accurately predicted poor comprehension by representatives ( p = .03 ) . Conclusions Patient information is frequently not communicated effectively to family members by ICU physicians . Physicians should strive to identify patients and families who require special attention and to determine how their personal style of interrelating with family members may impair communication |
12,146 | 23,728,643 | For women it remains uncertain whether sildenafil is more effective than placebo .
Data from three studies in men and women of bupropion 150 mg twice daily indicate a benefit over placebo on rating scale scores ( SMD 1.60 , 95 % CI 1.40 to 1.81 ) , but response rates in two studies of bupropion 150 mg once daily demonstrated no statistically significant difference in effect ( RR 0.62 , 95 % CI 0.09 to 4.41).Other augmentation strategies failed to demonstrate significant improvements in sexual dysfunction compared with placebo .
For men with antidepressant-induced erectile dysfunction , the addition of sildenafil or tadalafil appears to be an effective strategy .
For women with antidepressant-induced sexual dysfunction the addition of bupropion at higher doses appears to be the most promising approach studied so far | BACKGROUND Sexual dysfunction ( including altered sexual desire , orgasmic and ejaculatory dysfunction , erectile and other problems ) is a relatively common side effect of antidepressant medication .
These sexual side effects may compromise a person 's lifestyle and result in a lack of compliance with the prescribed antidepressant to the detriment of the person 's mental health .
A wide range of management strategies are possible to address this problem , including behavioural , psychological and pharmacological approaches .
To determine the effectiveness of management strategies for sexual dysfunction caused by antidepressants.2 .
To determine the adverse effects and acceptability of the different management strategies . | A triple-blind ( investigator , patient , statistician ) , r and omized , placebo-controlled , trial of Ginkgo biloba 240 mg daily was carried out . Following a 1-week control , it was given to 24 patients with sexual impairment due to antidepressant drugs . Efficacy analysis was carried out on eight males and five females on placebo and six males and five females on Ginkgo , completing the full 12 weeks of treatment . Not included were three subjects who dropped out after 6 weeks . A vali date d , sex (gender)-orientated question naire was recorded at - 1 , 0 , 1 , 3 , 6 , 9 and 12 weeks , and a non-blind follow-up for a further 6-weeks on Ginkgo . Hamilton anxiety and depression ratings were made at 0 , 6 and 12 weeks and simple global assessment s of alertness and memory . There were some spectacular individual responses in both groups , but no statistically significant differences , and no differences in side-effects Fifty partial and non-responders ( Clinical Global Impression-Sexual Function ( CGI-SF ) score>2 ) , out of 76 men who completed a 6-week , double-blind , placebo-controlled trial of sildenafil treatment for serotonergic antidepressant – associated sexual dysfunction , were eligible for an additional 6-week trial of open-label sildenafil ( 50 mg adjustable to 100 mg ) under the same protocol , with blind maintained to initial assignment . Participation ( double-blind and open-label ) required major depressive disorder in remission ( MDD-R ) and continuing antidepressant medication . Forty-three entered open-label study : 16/17 initially r and omized to sildenafil ( sildenafil/sildenafil ) and 27/33 initially r and omized to placebo ( placebo/sildenafil ) . Thirty-five of 43 ( 81 % ) achieved full response ( CGI-SF⩽2 ) : placebo/sildenafil 23/27 ( 85 % ) ; sildenafil/sildenafil 12/16 ( 75 % ) ; P<0.0001 for changes and P=0.4 between groups . Secondary measures of erectile function and overall satisfaction improved in both groups ( P<0.03 ) . Hamilton Depression Rating Scale scores improved ( placebo/sildenafil ; P⩽0.05 ) or remained stable ( sildenafil/sildenafil ) . In men with MDD-R who maintained antidepressant adherence , 81 % of double-blind partial and non-responders treated with open-label sildenafil responded fully BACKGROUND Sexual side effects are among the common reasons patients discontinue selective serotonin reuptake inhibitors ( SSRIs ) . While many antidotes have been proposed , few have been subjected to double-blind trials . Some evidence has suggested that bupropion may be an effective antidote for SSRI-induced sexual dysfunction . In this double-blind trial , the efficacy of a st and ard dose of bupropion sustained release ( SR ) is evaluated in the treatment of SSRI-induced sexual dysfunction . METHOD Patients with a history of SSRI-induced sexual side effects were r and omly assigned to adjunctive treatment with either bupropion SR 150 mg daily or placebo for 6 weeks . Assessment s of sexual function and interest included the Arizona Sexual Experiences Scale ( ASEX ) , Brief Index of Sexual Functioning , and a 10-point visual analogue scale . Efficacy was defined as a 50 % improvement on the ASEX at the end of 6 weeks . Data were collected from January 1999 to March 2001 . RESULTS Forty-one patients entered the study and completed the 6-week trial . No significant differences were seen between placebo and bupropion SR on the ASEX or on any measure of sexual functioning at the end of the trial . CONCLUSION A fixed dose of 150 mg/day of bupropion SR taken in the morning does not appear to be effective in the treatment of SSRI-induced sexual dysfunction . Additional trials will be required to define what role , if any , bupropion might have in the treatment of SSRI-induced sexual side effects Rationale Saffron ( Crocus sativus L. ) has shown aphrodisiac effects in some animal and human studies . Objectives To assess the efficacy and tolerability of saffron in fluoxetine-related sexual dysfunction . Methods This was a 4-week r and omized double-blind placebo-controlled study . Thirty-six married male patients with major depressive disorder whose depressive symptoms had been stabilized on fluoxetine and had subjective complaints of sexual impairment entered the study . The patients were r and omly assigned to saffron ( 15 mg twice per day ) or placebo for 4 weeks . International Index of Erectile Function scale was used to assess sexual function at baseline and weeks 2 and 4 . Results Thirty patients finished the study . Baseline characteristics as well as baseline and final depressive symptoms scores were similar between the two groups . Effect of time × treatment interaction on the total score was significant [ Greenhouse – Geisser-corrected , F ( 1.444 , 40.434 ) = 6.154 , P = 0.009 ] . By week 4 , saffron result ed in significantly greater improvement in erectile function ( P < 0.001 ) and intercourse satisfaction domains ( P = 0.001 ) , and total scores ( P < 0.001 ) than the placebo group . Effect of saffron did not differ significantly from that of placebo in orgasmic function ( P = 0.095 ) , overall satisfaction ( P = 0.334 ) , and sexual desire ( P = 0.517 ) domains scores . Nine patients ( 60 % ) in the saffron group and one patient ( 7 % ) in the placebo group achieved normal erectile function ( score > 25 on erectile function domain ) at the end of the study ( P value of Fisher ’s exact test = 0.005 ) . Frequency of side effects were similar between the two groups . Conclusions Saffron is a tolerable and efficacious treatment for fluoxetine-related erectile dysfunction Erectile dysfunction ( ED ) and depression are highly prevalent and frequently comorbid . Sildenafil effectively treats ED in men with depression and in men taking antidepressants . We evaluated the efficacy of sildenafil in men with depression in remission and ED . Patients with a history of ED when major depressive disorder ( MDD ) was diagnosed , which persisted after MDD was treated to remission , were r and omized to 12 weeks of treatment with sildenafil ( 50 mg , flexible ) or placebo . Efficacy was assessed using intercourse success rates , a global efficacy question ( Has treatment improved your erections ? ) , the International Index of Erectile Function ( IIEF ) and Life Satisfaction Checklist ( LSC ) . By week 12 , intercourse success rates were significantly higher among sildenafil- ( 74 % ) compared to placebo-treated patients ( 29 % ; P=0.0001 ) . About 83 % and 34 % of sildenafil- and placebo-treated patients , respectively , reported improved erections ( odds ratio=9.4 , P=0.0001 ) . IIEF scores in the sildenafil group ( n=83 ) were significantly improved compared to those in the placebo group ( n=85 ; P < 0.0001 ) . LSC sexual life item improved significantly among sildenafil- versus placebo-treated patients . The most frequently reported adverse events were transient and mild-to-moderate . Sildenafil is an effective and well-tolerated treatment for ED in patients with a history of ED at the time of MDD diagnosis , and which persisted after the MDD was treated to remission BACKGROUND The efficacy , tolerability , and effects on sexual function and satisfaction of nefazodone and sertraline were compared in a multicenter , r and omized , double-blind , parallel-group study in out patients with major depression . METHOD One hundred sixty patients , 18 years of age or older , who met DSM-III-R criteria for single or recurrent nonpsychotic major depressive episodes were r and omly assigned to 6 weeks of treatment with either nefazodone ( 100 - 600 mg/day ) or sertraline ( 50 - 200 mg/day ) . Symptoms were assessed before and during treatment using the 17-item Hamilton Rating Scale for Depression ( HAM-D-17 ) , Clinical Global Impressions ( CGI ) Improvement scale , the CGI Severity of Illness scale , and a sexual function question naire . RESULTS Of 143 patients evaluable for efficacy , 72 received sertraline and 71 received nefazodone . The mean modal daily dose at endpoint was 148 mg for sertraline and 456 mg for nefazodone . Analysis of efficacy measures ( HAM-D-17 and CGI ) showed consistent and comparable improvement in symptoms of depression for both treatment groups . Sertraline had negative effects on sexual function and satisfaction in both men and women , and nefazodone had no adverse effect on sexual well-being . Safety assessment s based on adverse events , vital sign measurements , electrocardiographs , physical examinations , and clinical laboratory tests revealed no serious adverse events or organ toxicity associated with nefazodone or sertraline administration . CONCLUSION Nefazodone and sertraline are well tolerated , and there was no statistically significant difference in their antidepressant activity . Sertraline treatment has negative effects on sexual function and performance in both sexes , while nefazodone has none . These findings may have clinical implication s when choosing antidepressant therapy CONTEXT Antidepressant-associated sexual dysfunction is a common adverse effect that frequently results in premature medication treatment discontinuation and for which no treatment has demonstrated efficacy in women . OBJECTIVE To evaluate the efficacy of sildenafil for sexual dysfunction associated with selective and nonselective serotonin reuptake inhibitors ( SRIs ) in women . DESIGN , SETTING , AND PARTICIPANTS An 8-week prospect i ve , parallel-group , r and omized , double-blind , placebo-controlled clinical trial conducted between September 1 , 2003 , and January 1 , 2007 , at 7 US research centers that included 98 previously sexually functioning , premenopausal women ( mean [ SD ] age 37.1 [ 6 ] years ) whose major depression was remitted by SRIs but who were also experiencing sexual dysfunction . INTERVENTION Forty-nine patients were r and omly assigned to take sildenafil or placebo at a flexible dose starting at 50 mg adjustable to 100 mg before sexual activity . MAIN OUTCOME MEASURES The primary outcome measure was the mean difference in change from baseline to study end ( ie , lower ordinal score ) on the Clinical Global Impression sexual function scale . Secondary measures included the Female Sexual Function Question naire , the Arizona Sexual Experience scale-female version , the University of New Mexico Sexual Function Inventory-female version , a sexual activity event log , and the Hamilton Depression Rating scale . Hormone levels were also assessed . RESULTS In an intention-to-treat analysis , women treated with sildenafil had a mean Clinical Global Impression-sexual function score of 1.9 ( 95 % confidence interval [ CI ] , 1.6 - 2.3 ) compared with those taking placebo ( 1.1 ; 95 % CI , 0.8 - 1.5 ) , with a mean end point difference of 0.8 ( 95 % CI , 0.6 - 1.0 ; P = .001 ) . Assigning baseline values carried forward to the 22 % of patients who prematurely discontinued result ed in a mean end point in the sexual function score of 1.5 ( 95 % CI , 1.1 - 1.9 ) among women taking sildenafil compared with 0.9 ( 95 % CI , 0.6 - 1.3 ) among women taking placebo with a mean end point difference of 0.6 ( 95 % CI , 0.3 - 0.8 ; P = .03 ) . Baseline endocrine levels were within normal limits and did not differ between groups . The mean ( SD ) Hamilton scores for depression remained consistent with remission in both groups ( 4.0 [ 3.6 ] ; P = .90 ) . Headache , flushing , and dyspepsia were reported frequently during treatment , but no patients withdrew because of serious adverse effects . CONCLUSION In this study population , sildenafil treatment of sexual dysfunction in women taking SRIs was associated with a reduction in adverse sexual effects . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00375297 To evaluate the possible influence of buspirone on sexual dysfunction in depressed patients treated with a selective serotonin reuptake inhibitor ( SSRI ) , we analyzed data from a placebo-controlled trial design ed to explore the efficacy of buspirone as add-on treatment for patients not responding to an SSRI alone . At baseline , all patients met the criteria for a major depressive episode according to DSM-IV and had received citalopram or paroxetine during a minimum of 4 weeks without responding to the treatment . Buspirone ( flexible dosage , 20 - 60 mg/day ) or placebo was added to the SSRI for 4 weeks ; the mean daily dose of buspirone at endpoint was 48.5 mg ( SD = 1.0 ) . Sexual dysfunction was evaluated using a structured interview . Before starting medication with buspirone or placebo , 40 % ( 47 of 117 ) reported at least one kind of sexual dysfunction ( decreased libido , ejaculatory dysfunction , orgasmic dysfunction ) . During the 4 weeks of treatment , approximately 58 % of subjects treated with buspirone reported an improvement with respect to sexual function ; in the placebo group , the response rate was 30 % . The difference between placebo and active drug treatment was more pronounced in women than in men . The response was obvious during the first week , with no further improvement during the course of the study . It is suggested that the effect of buspirone on sexual dysfunction is a result of a reversal of SSRI-induced sexual side effects rather than of an antidepressant effect of the drug PURPOSE To investigate whether bethanecol chloride may be an alternative for the clinical management of clomipramine-induced orgasmic dysfunction , reported to occur in up to 96 % of male users . METHODS In this study , 12 fully remitted panic disorder patients , complaining of severe clomipramine-induced ejaculatory delay , were r and omly assigned to either bethanecol chloride tablets ( 20 mg , as needed ) or placebo in a r and omized , double-blind , placebo-controlled , two-period crossover study . A visual analog scale was used to assess severity of the orgasmic dysfunction . RESULTS A clear improvement was observed in the active treatment period . No placebo or carry-over effects were observed . CONCLUSION These findings suggest that bethanecol chloride given 45 minutes before sexual intercourse may be useful for clomipramine-induced orgasmic dysfunction in males Ginkgo biloba extract ( GBE ) facilitates blood flow , influences nitric oxide systems , and has a relaxant effect on smooth muscle tissue . These processes are important to the sexual response in women and , hence , it is feasible that GBE may have a therapeutic effect . The present study was the first to provide an empirical examination of the effects of both short- and long-term GBE administration on subjective and physiological ( vaginal photoplethysmography ) measures of sexual function in women with Sexual Arousal Disorder . A single dose of 300 mg GBE had a small but significant facilitatory effect on physiological , but not subjective , sexual arousal compared to placebo in 99 sexually dysfunctional women . The long-term effects of GBE on sexual function were assessed in 68 sexually dysfunctional women who were r and omly assigned to 8 weeks treatment of either ( 1 ) GBE ( 300 mg/daily ) , ( 2 ) placebo , ( 3 ) sex therapy which focused on training women to attend to genital sensations , or ( 4 ) sex therapy plus GBE . When combined with sex therapy , but not alone , long-term GBE treatment significantly increased sexual desire and contentment beyond placebo . Sex therapy alone significantly enhanced orgasm function compared with placebo . Long-term GBE administration did not significantly enhance arousal responses beyond placebo . It was concluded that ( 1 ) neither short- or long-term administration of GBE alone substantially impacts sexual function in women , ( 2 ) a substantial placebo effect on sexual function exists in women with sexual concerns , and ( 3 ) teaching women to focus on genital sensations during sex enhances certain aspects of women ’s sexual functioning A double-blind parallel-group comparison study of moclobemide versus doxepin in 237 patients with major depression confirmed that moclobemide was equal in efficacy and better tolerated than doxepin . It was less sedating and caused fewer anticholinergic adverse events as measured by the UKU side-effect rating scale . Unexpectedly , moclobemide therapy more often than doxepin result ed in increased sexual desire . An exploratory analysis of UKU-measured symptoms of impaired sexual function prior to commencement of the study revealed that moclobemide more often than doxepin led to an improvement of reduced libido and impaired erection , ejaculation and orgasm . This finding is compatible with the assumption that there is a greater likelihood that the anticholinergic reuptake inhibitor doxepin has a higher risk of impairing sexual function than the non-anticholinergic RIMA moclobemide . A single case report of moclobemide-induced sexual hyperarousal supports the alternative assumption that moclobemide has a specific sexually stimulative effect in depression OBJECTIVE Few controlled trials of pharmacologic intervention in women with antidepressant-associated sexual dysfunction have been reported , and there is uncertainty about the usefulness of putative treatments and the assessment method ologies . The authors evaluated the efficacy of buspirone and amantadine in the treatment of sexual dysfunction associated with fluoxetine administration . METHOD Women who had been successfully treated with fluoxetine for at least 8 weeks and who had reported a deterioration in sexual function not present before the initiation of fluoxetine entered a 4-week assessment period . After assessment they were r and omly assigned to an 8-week treatment trial with buspirone ( N=19 ) , amantadine ( N=18 ) , or placebo ( N=20 ) . Outcomes were assessed by using a patient-rated daily diary and a clinician-rated structured interview . RESULTS While the amantadine-treated women did report significantly greater improvements in energy levels than women in the placebo group , all treatment groups experienced improvement in overall sexual function as well as in most individual measures . There were no statistically significant differences among the three groups . CONCLUSIONS Neither buspirone nor amantadine was more effective than placebo in ameliorating antidepressant-associated sexual dysfunction . All groups experienced marked nonspecific improvement during treatment , which suggests the importance of placebo-controlled trials for this condition The results of a r and omized clinical trial can be reported using relative and /or absolute estimators of treatment effect . These various measures convey different information , and the choice can influence the physician 's appreciation of the size of treatment effect and , subsequently , treatment decisions . We compare the estimators with respect to the clinical ly relevant information conveyed to physicians , and identify which clinical questions can and can not be answered directly by each . We also identify opportunities for misinterpretation when one estimator is substituted for another , or when an estimator is mislabeled . Clinical ly important questions are addressed most directly by reporting both relative and absolute effects using relative risk and its complement , relative risk reduction , and risk difference and its reciprocal , number needed to treat . This is true of estimates of treatment effect derived from a single trial and also from meta- analysis of a group of trials . Because the control group 's risk affects the numerical value of the odds ratio , the odds ratio can not substitute for the risk ratio in conveying clinical ly important information to physicians . This is especially important when large treatment effects are shown in trials carried out in population s at high baseline risk BACKGROUND Several different classes of antidepressants have been associated with sexual adverse effects . This double-blind , r and omized trial compared the effects of nefazodone and sertraline on reemergence of sexual dysfunction in depressed patients who had experienced sexual dysfunction as a result of sertraline treatment . Depressive symptoms were also monitored . METHOD One hundred five patients with DSM-III-R major depressive episode who were experiencing sexual dysfunction attributable to sertraline ( 100 mg/day ) were screened for entry . Eligible patients entered a 1-week washout period that was followed by a 7- to 10-day single-blind placebo phase . Patients without symptoms of sexual dysfunction at the end of the single-blind placebo phase were r and omly assigned to receive double-blind treatment with either nefazodone ( 400 mg/day ) or sertraline ( 100 mg/day ) for 8 weeks . RESULTS Nearly 3 times more sertraline-treated patients ( 76 % ; 25/33 ) experienced reemergence of sexual dysfunction ( ejaculatory and /or orgasmic difficulty ) than did nefazodone-treated patients ( 26 % ; 10/39 ) ( p < .001 ) . In addition , patients treated with nefazodone were more satisfied with their sexual functioning than were patients treated with sertraline . Both treatment groups demonstrated a similar and sustained improvement in depressive symptoms . Both drugs were well tolerated , and the overall incidence of adverse reactions was similar for both treatment groups ; however , 9 sertraline-treated patients ( 26 % ) discontinued because of adverse events compared with 5 nefazodone-treated patients ( 12 % ) . Of the patients discontinuing therapy for adverse events , 5 of the sertraline-treated patients did so because of sexual dysfunction reported as an adverse event , whereas only 1 of the nefazodone-treated patients discontinued therapy secondary to sexual dysfunction . CONCLUSION In this sample of patients with major depression who had recovered from sexual dysfunction induced by treatment with sertraline , nefazodone treatment result ed in significantly less reemergence of sexual dysfunction than did renewed treatment with sertraline and provided continued antidepressant activity & NA ; Antidepressant induced sexual dysfunction is a common adverse event that is particularly evident with serotonergic antidepressants . There is a paucity of clinical trial evidence on the treatment of this problem . While there is some evidence of involvement of the serotonin ( 5‐HT2 ) receptor subtype in this phenomenon , other serotonergic receptor systems are not well studied . In this trial , 35 patients on maintenance therapy with a variety of serotonergic antidepressants , who reported antidepressant induced sexual dysfunction , were enrolled . Patients were given both granisetron 1 mg , and sumatriptan 100 mg , in a crossover design , to be used 1 h before intercourse . Sexual dysfunction was measured using the Feiger scale . There was a high dropout rate in the trial , reflecting both embarrassment with the pharmacological treatment of sexual dysfunction and difficulties with planning and timing the medication . Nevertheless , there was a significant effect of granisetron in this study , with scores decreasing from 23.7 ( SD 2.52 ) to 16.0 ( SD 6.42 ) on the Feiger scale ( n = 14 , P = 0.001 , Wilcoxon sign rank test ) . Sumatriptan failed to show a significant change from baseline at the 0.01 level of significance . While the small sample size , high dropout rates and open label design are limitations to this study , it suggests efficacy of the granisetron in antidepressant induced sexual dysfunction and the role of the 5‐HT3 receptor in this phenomenon BACKGROUND Case reports and open studies have reported beneficial therapeutic effects of adding buspirone to a selective serotonin reuptake inhibitor ( SSRI ) in the management of treatment-refractory depression . This is the first placebo-controlled study to evaluate the efficacy and safety of this combination . METHOD One hundred nineteen patients ( 82 women , 37 men ) who fulfilled criteria for a major depressive episode according to DSM-IV and who had failed to respond to a minimum of 4 weeks ( mean = 211 days ) of treatment with citalopram or paroxetine were r and omly assigned to 4 weeks of treatment with an SSRI plus buspirone ( N = 58 ) or an SSRI plus placebo ( N = 61 ) . In addition , 97 patients participated in an optional open-label post study treatment phase with the SSRI plus buspirone for 2 weeks . The primary outcome measure was the score on the Clinical Global Impressions-Improvement ( CGI-I ) scale . RESULTS A total of 50.9 % of patients in the buspirone group and 46.7 % in the placebo group responded after 4 weeks of treatment . The difference in response rate was not statistically significant . No statistically significant differences were found in the frequency of adverse events . At the follow-up of the open SSRI plus buspirone treatment , 69.4 % of patients had responded . CONCLUSION Adding buspirone to an SSRI is a safe and well-tolerated drug regimen . This study failed to demonstrate any difference in efficacy between buspirone or placebo augmentation of an SSRI . It could be argued , however , that the study was inconclusive due to the unusually high placebo response BACKGROUND Sexual side effects are a common and bothersome reaction to selective serotonin reuptake inhibitors ( SSRIs ) , frequently leading to cessation of treatment . Mirtazapine , an alpha2-adrenoceptor and serotonin-2/3 receptor antagonist , appears to cause few sexual problems . METHOD Nineteen patients ( 12 women and 7 men ) , with SSRI-induced sexual dysfunction who were in remission from major depressive disorder ( total Hamilton Rating Scale for Depression [ HAM-D ] score < or = 10 ) , were switched to open-label mirtazapine for up to 6 weeks . Mirtazapine was titrated from 7.5 mg to 45 mg daily , as tolerated . Sexual functioning was measured weekly with the Arizona Sexual Experiences Scale ( ASEX ) , and depression was measured weekly with the HAM-D. RESULTS Eleven patients ( 58 % ) had a return of normal sexual functioning ( mean + /- SD ASEX score = 12+/-3 ) , and another 2 ( 11 % ) reported significant improvement in sexual functioning ( mean ASEX score reduced from 24+/-1 to 20+/-0 ) . All nineteen patients maintained their antidepressant response ( HAM-D score after 6 weeks of mirtazapine = 6+/-3 ) . The most commonly reported side effects ( using moderate/severe rating on a symptom checklist ) were initial sedation ( N = 3 ) , irritability ( N = 6 ) , and muscle soreness and stiffness ( N = 3 ) . Weight gain of 10 to 20 lb ( 4.5 - 9 kg ) was seen in 3 patients ( 2 women and 1 man ) . CONCLUSION Mirtazapine is an effective antidepressant for many patients experiencing SSRI-induced sexual dysfunction OBJECTIVES To develop Patient and Partner versions of a psychometrically sound question naire , the EDITS ( Erectile Dysfunction Inventory of Treatment Satisfaction ) , to assess satisfaction with medical treatments for erectile dysfunction . METHODS Treatment satisfaction differs from treatment efficacy as it focuses on a person 's subjective evaluation of treatment received . Twenty-nine items representing the domain of treatment satisfaction for men and 20 representing partner satisfaction were generated . Two independent sample s of 28 and 29 couples completed all items at two points in time . Spearman rank-order correlations were derived to assess test-retest reliability and couple coefficients of validity . Internal consistency coefficients were calculated for both Patient and Partner versions and a content validity panel was used to analyze content validity . RESULTS Only items that met all the following criteria were selected to comprise the final question naires : ( a ) range of response four or more out of five ; ( b ) test-retest reliability greater than 0.70 ; ( c ) ratings by at least 70 % of the content validity panel as belonging in and being important for the domain ; and ( d ) significant correlation between the subjects ' and partners ' responses . Eleven patient items met criteria and formed the Patient EDITS ; five partner items met criteria and formed the Partner EDITS . Scores on the two inventories were normally distributed with internal consistencies of 0.90 and 0.76 , respectively . Test-retest reliability for the Patient EDITS was 0.98 ; for the Partner EDITS , it was 0.83 . CONCLUSIONS Reliability and validity were well established , enabling the EDITSs to be used to assess satisfaction with treatment modalities for erectile dysfunction and to explore the impact of patient and partner satisfaction on treatment continuation OBJECTIVE Saffron ( Crocus sativus L. ) has shown beneficial aphrodisiac effects in some animal and human studies . The aim of the present study was to assess the safety and efficacy of saffron on selective serotonin reuptake inhibitor-induced sexual dysfunction in women . METHODS This was a r and omized double-blind placebo-controlled study . Thirty-eight women with major depression who were stabilized on fluoxetine 40 mg/day for a minimum of 6 weeks and had experienced subjective feeling of sexual dysfunction entered the study . The patients were r and omly assigned to saffron ( 30 mg/daily ) or placebo for 4 weeks . Measurement was performed at baseline , week 2 , and week 4 using the Female Sexual Function Index ( FSFI ) . Side effects were systematic ally recorded . RESULTS Thirty-four women had at least one post-baseline measurement and completed the study . Two-factor repeated measure analysis of variance showed significant effect of time × treatment interaction [ Greenhouse-Geisser 's corrected : F(1.580 , 50.567 ) = 5.366 , p = 0.012 ] and treatment for FSFI total score [ F(1 , 32 ) = 4.243 , p = 0.048 ] . At the end of the fourth week , patients in the saffron group had experienced significantly more improvement in total FSFI ( p < 0.001 ) , arousal ( p = 0.028 ) , lubrication ( p = 0.035 ) , and pain ( p = 0.016 ) domains of FSFI but not in desire ( p = 0.196 ) , satisfaction ( p = 0.206 ) , and orgasm ( p = 0.354 ) domains . Frequency of side effects was similar between the two groups . CONCLUSIONS It seems saffron may safely and effectively improve some of the fluoxetine-induced sexual problems including arousal , lubrication , and pain A significant number of patients undergoing treatment with selective serotonin reuptake inhibitors ( SSRIs ) report sexual dysfunction . SSRI-induced sexual dysfunction adversely affects quality of life and patient adherence to and compliance with treatment regimens . This trial examined the efficacy and safety of adjunctive bupropion in the treatment of SSRI-induced female sexual dysfunction . Sexual function was assessed by using the sexual function domains of the Female Sexual Function Index ( primary efficacy outcome measure ) and the Clinical Global Impression Scale adapted for sexual function ( secondary efficacy outcome measure ) . End point treatment satisfaction was assessed using a Visual Analog Scale . A total of 218 women ( 25–45 years old ) with SSRI-induced sexual dysfunction were r and omized to receive 12 weeks of double-blind fixed dosed treatment with bupropion sustained release 150 mg b.i.d . ( n = 109 ) or placebo ( n = 109 ) . The mean ( SD ) for Female Sexual Function Index total score was higher in the bupropion sustained release group ( 25.9 ( 5.12 ) , 95 % confidence interval ( CI ) 22.2–29.4 ) than in the placebo group ( 17.2 ( 4.9 ) , 95 % CI 15.8–20.1 ) ( p = 0.001 ) . Mean ( SD ) Clinical Global Impression Scale score for the bupropion group ( 2.4 ( 0.6 ) , 95 % CI 2.0–3.6 ) was significantly lower than that for the placebo group ( 4.2 ( 0.8 ) , 95 % CI 3.4–5.4 ) ( p = 0.001 ) . At the end of the trial the mean ( SD ) scores for desire ( 4.1 ( 0.7 ) , 95 % CI 3.5–4.8 ) ( p = 0.001 ) , arousal ( 4.4 ( 0.6 ) , 95 % CI 3.7–4.8 ) ( p = 0.01 ) , lubrication ( 4.4 ( 0.4 ) , 95 % CI 3.3–4.8 ) ( p = 0.001 ) , orgasm ( 4.4 ( 0.5 ) , 95 % CI 3.7–4.7 ) ( p = 0.001 ) , and satisfaction ( 4.2 ( 0.7 ) , 95 % CI 3.4–4.8 ) ( p = 0.001 ) were significantly higher in the bupropion group . The highest improvement was observed in sexual desire , followed by lubrication . Compared with baseline , desire and lubrication domains increased by 86.4 % ( 95 % CI 64.9–102.2 % , p = 0.001 ) and 69.2 % ( 95 % CI 44.7–82.6 % , p = 0.001 ) in the bupropion group . Adjunctive treatment with bupropion sustained release during a 12-week period significantly improved key aspects of sexual function in women with SSRI-induced sexual dysfunction OBJECTIVE To evaluate the efficacy of short-term treatment with sildenafil citrate in men with serotonin reuptake inhibitor (SRI)-associated erectile dysfunction ( ED ) . METHOD Men ( aged > or=18 years ) with major depressive disorder ( MDD ; DSM-IV criteria ) in remission and taking SRIs who experienced SRI-associated ED were enrolled in this multicenter , 6-week , r and omized , flexible-dose , double-blind , placebo-controlled trial . The primary study measures were questions 3 ( Q3 : frequency of penetration ) and 4 ( Q4 : frequency of maintained erections after penetration ) of the International Index of Erectile Function ( IIEF ) question naire . Secondary study measures were all other questions and domains of the IIEF , the Erectile Dysfunction Index of Treatment Satisfaction ( EDITS ) , a global efficacy question naire ( GEQ ) , and a patient-maintained event log of sexual activity . RESULTS Patients receiving sildenafil ( N=71 ) versus placebo ( N=71 ) reported significantly higher mean+/-SE scores on Q3 ( 3.9+/-0.2 vs. 3.1+/-0.2 , p=.003 ) and Q4 ( 3.7+/-0.2 vs. 2.8+/-0.2 , p<.001 ) of the IIEF and significantly higher scores on all domains of the IIEF . Patients receiving sildenafil also reported significantly improved scores on all questions of the EDITS question naire ( p<.02 ) and the GEQ ( p<.0001 ) and an increased number of successful sexual intercourse attempts per week ( p<.0001 ) compared with patients receiving placebo . All patients remained in MDD remission ( score < or=10 on the Hamilton Rating Scale for Depression ) . Adverse events in patients taking sildenafil ( vs. placebo ) were headache ( 9 % vs. 9 % ) , dyspepsia ( 9 % vs. 1 % ) , anxiety ( 6 % vs. 4 % ) , and abnormal vision ( 3 % vs. 0 % ) . CONCLUSIONS Short-term ( 6-week ) administration of sildenafil was well tolerated and significantly improved erectile function and overall sexual satisfaction in men with ED associated with SRI therapy for MDD . Sildenafil may be successfully used to treat SRI-associated ED without interruption of antidepressant therapy BACKGROUND Sexual side effects are commonly associated with serotonin reuptake inhibitor ( SRI ) therapy . The mechanism underlying SRI-induced sexual dysfunction has been hypothesized to be mediated by direct serotonergic effects . Evidence from open-label reports suggests that cyproheptadine , nefazodone , mirtazapine , and mianserin , which block one or more serotonin receptors , may reverse sexual side effects . The current study was a prospect i ve , r and omized , crossover trial comparing granisetron , a serotonin-3 antagonist , with placebo in out patients who developed sexual dysfunction during SRI treatment . METHOD Thirty-one out patients who were currently experiencing sexual dysfunction associated with SRIs were r and omly assigned to double-blind treatment with granisetron ( 1 - 1.5 mg ) or placebo for use 1 to 2 hours prior to sexual activity . Patients rated sexual symptoms after each trial using the Sexual Side Effect Scale ( SSES ) . After 4 trials of the medication , patients crossed over to the other treatment for 4 more trials . RESULTS Twenty patients received at least 1 dose of placebo and granisetron . Analysis by repeated- measures analysis of variance showed no significant effects of granisetron relative to placebo . Significant improvement between baseline and treatment-phase SSES scores was observed for both granisetron ( p = .0004 ) and placebo ( p = .0081 ) . The study medication was generally well tolerated . CONCLUSION The results of this study do not support the efficacy of granisetron ( 1 - 2 mg ) in the treatment of SRI-associated sexual side effects . A significant placebo response may be associated with the treatment of SRI-induced sexual dysfunction OBJECTIVE This study was an evaluation of whether sildenafil citrate is effective for the treatment of erectile dysfunction in men taking concomitant serotonin-reuptake-inhibiting antidepressants . METHOD A retrospective sub analysis of combined data from 10 phase II/III double-blind , placebo-controlled , fixed- and flexible-dose trials ( 12 - 26 weeks ) identified a group of men with erectile dysfunction receiving 5 to 200 mg/day of sildenafil ( N=65 ) or placebo ( N=33 ) and concomitant serotonin-reuptake-inhibiting antidepressants . Efficacy was measured by responses to questions from the International Index of Erectile Function on ability to achieve erection , ability to maintain erection , ejaculation frequency , orgasm frequency , and sexual desire . RESULTS Patients with erectile dysfunction receiving sildenafil and concomitant serotonergic antidepressants had significantly greater improvements in ability to achieve and maintain an erection , frequency of ejaculation , and orgasm frequency than did patients receiving placebo , without increased sexual desire . CONCLUSIONS Sildenafil significantly improved erectile dysfunction in patients taking concomitant serotonergic antidepressants There are limited data to indicate effective treatment strategies for antidepressant-related sexual dysfunction , in particular for patients with treatment-resistant major depression . We subanalyzed our published data whether augmentation with methylpheni date extended release ( OROS MPH ) improved sexual dysfunction associated with antidepressants in patients with treatment-resistant major depression . The primary efficacy measure was the change in Arizona Sexual Experiences Survey ( ASEX ) from baseline to end of treatment in an intent-to-treat analysis with last observation carried forward approach . There were no significant differences between the 2 groups in terms of changes in ASEX scores over time ( F1,35 = 1.14 ; P = 0.32 ) , although the numerical decrease in ASEX score was greater in OROS MPH ( mean change , −4.5 ; 20.1 % decrease ) than in the placebo group ( mean change , −0.6 ; 2.6 % decrease ) . Augmentation with OROS MPH showed no statistically significant benefit in antidepressant-related sexual dysfunction , although addition of OROS MPH to antidepressants did not worsen preexisting sexual dysfunction . Adequately powered controlled trials are needed to fully evaluate the efficacy of OROS MPH in this area We sought to determine whether maca , a Peruvian plant , is effective for selective‐serotonin reuptake inhibitor (SSRI)‐induced sexual dysfunction . We conducted a double‐blind , r and omized , parallel group dose‐finding pilot study comparing a low‐dose ( 1.5 g/day ) to a high‐dose ( 3.0 g/day ) maca regimen in 20 remitted depressed out patients ( mean age 36 ± 13 years ; 17 women ) with SSRI‐induced sexual dysfunction . The Arizona Sexual Experience Scale ( ASEX ) and the Massachusetts General Hospital Sexual Function Question naire ( MGH‐SFQ ) were used to measure sexual dysfunction . Ten subjects completed the study , and 16 subjects ( 9 on 3.0 g/day ; 7 on 1.5 g/day ) were eligible for intent‐to‐treat ( ITT ) analyses on the basis of having had at least one postbaseline visit . ITT subjects on 3.0 g/day maca had a significant improvement in ASEX ( from 22.8 ± 3.8 to 16.9 ± 6.2 ; z = −2.20 , P= 0.028 ) and in MGH‐SFQ scores ( from 24.1 ± 1.9 to 17.0 ± 5.7 ; z = −2.39 , P= 0.017 ) , but subjects on 1.5 g/day maca did not . Libido improved significantly ( P < 0.05 ) for the ITT and completer groups based on ASEX item # 1 , but not by dosing groups . Maca was well tolerated . Maca root may alleviate SSRI‐induced sexual dysfunction , and there may be a dose‐related effect . Maca may also have a beneficial effect on libido BACKGROUND Many agents have been proposed as potential treatments for SSRI-associated sexual dysfunction , but few placebo-controlled trials have been reported . METHOD After a 1-month baseline evaluation , pre-menopausal women with moderate to severe sexual dysfunction associated with the institution of fluoxetine therapy were r and omized to augmentation therapy with placebo ( N=39 ) , mirtazapine ( N=36 ) , yohimbine ( N=35 ) or olanzapine ( N=38 ) for a 6-week period . Outcomes were measured using a daily diary , a biweekly self-report assessment , and a computer assisted structured interview . RESULTS At baseline , orgasm was most severely impaired . After 6 weeks , there was statistically significant improvement on most measures for the overall group of patients , however there were few differences between treatment groups . Isolated treatment differences were observed for the patient self-report of overall sexual function ( olanzapine superior to placebo ) and the structured interview sexual satisfaction item ( mirtazapine inferior to placebo ) . CONCLUSION No drug assessed was consistently associated with differences from placebo . The results of the study do not support uncontrolled reports of efficacy for these agents in premenopausal women OBJECTIVES To evaluate the efficacy and safety of tadalafil in men with treatment-emergent sexual dysfunction due to serotonin reuptake inhibitors . METHODS The present prospect i ve , double-blind , 12-week study , r and omized in a 1:1 ratio to tadalafil 20 mg or placebo taken on dem and , included 50 men . The efficacy measures were the changes in total and domain scores of the International Index of Erectile Function question naire , Sexual Encounter Profile diary questions 2 - 6 , and the Global Assessment questions ( GAQs ) 1 and 2 . The safety analyses included the evaluation of adverse events , vital signs , serum chemistry results , and electrocardiography findings . RESULTS For the patients who took tadalafil 20 mg , the net median score change from baseline to the endpoint compared with placebo was 26 for the 15-item International Index of Erectile Function ; 10 , 4 , 4 , 3 , and 3 for the erectile function , intercourse satisfaction , overall satisfaction , orgasmic function , and sexual desire domains ; and 3 and 5 points for " yes " responses to the Sexual Encounter Profile 2 and Sexual Encounter Profile 3 questions , respectively . All comparisons between tadalafil and placebo were significant ( P < .001 ) . At the endpoint , 92 % of the tadalafil group responded affirmatively to both GAQs 1 and 2 compared with 8 % of the placebo group ( P < .001 , for each ) . In the safety measures , no clinical ly significant changes attributable to tadalafil use were found . CONCLUSIONS Tadalafil 20-mg treatment significantly improved sexual function in patients who were taking serotonin reuptake inhibitors for depression , with mild to moderate , well-tolerable adverse events BACKGROUND Sexual dysfunction is a known side effect of antidepressant treatment ( ADT ) , affecting up to 58 - 73 % of those who receive ADT , potentially affecting antidepressant adherence . Consequently , it is vital to develop novel treatments that target antidepressant-induced sexual dysfunction . METHODS We examined whether adjunctive S-adenosyl-l-methionine ( SAMe ) is associated with greater improvement in sexual functioning than adjunctive placebo by measuring changes in sexual functioning using the Massachusetts General Hospital-Sexual Functioning Question naire ( MGH-SFQ ) during a 6-week , single-center , r and omized , double-blind trial of SAMe augmentation for SSRI/SNRI- nonresponders . RESULTS Controlling for the degree of arousal dysfunction at baseline as well as the degree of change in HDRS-17 scale scores during the course of the study , men treated with adjunctive SAMe demonstrated significantly lower arousal dysfunction at endpoint than those treated with adjunctive placebo . In addition , controlling for the degree of erectile dysfunction at baseline as well as the degree of change in HDRS-17 scale scores , men treated with adjunctive SAMe demonstrated significantly lower erectile dysfunction at endpoint than those treated with adjunctive placebo . CONCLUSIONS In the present study , we have observed that adjunctive SAMe can have positive benefit on male arousal and erectile dysfunction , independent of improvement in depressive symptoms . These findings are preliminary , and warrant replication . CLINICAL TRIALS.GOV IDENTIFIER : NCT00093847 ; titled ' Optimizing the Effectiveness of Selective Serotonin Reuptake Inhibitors ( SSRIs ) in Treatment-Resistant Depression ' , accessible at : http:// clinical trials.gov/ct2/show/NCT00093847 OBJECTIVE The incidence of sexual dysfunction due to antidepressant drugs reported in pre-marketing clinical efficacy trials is often several times lower than in subsequent clinical experiences and independent reports . Although it is commonly believed that the reason for this discrepancy is that the nonleading questions employed in conventional clinical trials underestimate sexual dysfunction while the direct question ing used in independent trials provides more accurate data , few studies have actually compared these 2 methods . METHOD In this study , 119 patients with a DSM-IV-defined major depressive episode ( 82 women and 37 men ) who had been treated with but not responded to a selective serotonin reuptake inhibitor ( SSRI ; either citalopram or paroxetine ) were assessed regarding sexual functioning by means of open-ended questions and direct question ing at baseline ( after SSRI treatment only ) and after 4 weeks of SSRI treatment plus buspirone or placebo . RESULTS More patients reported sexual dysfunction in response to direct question ing ( 41 % ) as compared with spontaneous report ( 6 % ) ( p < .001 ) . Sexual dysfunction correlated with the duration of the depressive episode , but not with age , dose of SSRI , plasma level of SSRI , duration of SSRI treatment , or any measurement of depression . No statistically significant differences regarding the incidence of sexual dysfunction were found between the citalopram and the paroxetine groups . CONCLUSION Open-ended questions are an insufficient tool to estimate sexual dysfunction , and premarketing clinical trials should therefore include basic explicit assessment s. The failure to find a correlation between treatment duration and sexual dysfunction adds to the notion that sexual side effects due to SSRIs do not abate over time OBJECTIVE This study reports the results of a placebo-controlled , double-blind comparison of bupropion sustained release ( SR ) as an antidote for sexual dysfunction versus placebo in 42 patients with selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction . Exploratory analyses of the association of testosterone and sexual functioning in women in the study were also performed . METHOD Patients with DSM-IV major depression who experienced a therapeutic response to any SSRI and were experiencing medication-induced global or phase-specific sexual dysfunction , as measured by the Changes in Sexual Functioning Question naire ( CSFQ ) , were r and omly assigned to receive either bupropion SR 150 mg b.i.d . or placebo for 4 weeks in addition to the SSRI . Total testosterone levels were assessed at baseline and week 4 . RESULTS The difference in global sexual functioning , based on the total CSFQ score , was not statistically significant between the 2 groups at week 4 , nor were differences in orgasm , desire/ interest as measured by sexual thoughts , or self-reported arousal . There was a statistically significant difference between the 2 groups at week 4 in desire as measured by self-report feelings of desire and frequency of sexual activity . Desire/ frequency showed a significantly greater improvement among those patients receiving bupropion SR compared with placebo ( Wilk 's F = 5.47 , df = 1 , p = .024 ) . Frequency was significantly correlated to total testosterone level at baseline ( r = 0.36 , p = .027 ) and at week 4 ( r = 0.41 , p = .025 ) . CONCLUSIONS Bupropion SR , as an effective antidote to SSRI-induced sexual dysfunction , produced an increase in desire to engage in sexual activity and frequency of engaging in sexual activity compared with placebo . A larger study is needed to further investigate this finding Exogenous testosterone therapy has psychotropic effects and has been proposed as an antidepressant augmentation strategy for depressed men . We sought to assess the antidepressant effects of testosterone augmentation of a serotonergic antidepressant in depressed , hypogonadal men . For this study , we recruited 100 medically healthy adult men with major depressive disorder showing partial response or no response to an adequate serotonergic antidepressant trial during the current episode and a screening total testosterone level of 350 ng/dL or lower . We r and omized these men to receive testosterone gel or placebo gel in addition to their existing antidepressant regimen . The primary outcome measure was the Hamilton Depression Rating Scale ( HDRS ) score . Secondary measures included the Montgomery-Asberg Depression Rating Scale , the Clinical Global Impression Scale , and the Quality of Life Scale . Our primary analysis , using a mixed effects linear regression model to compare rate of change of scores between groups on the outcome measures , failed to show a significant difference between groups ( mean [ 95 % confidence interval ] 6-week change in HDRS for testosterone vs placebo , −0.4 [ −2.6 to 1.8 ] ) . However , in one exploratory analysis of treatment responders , we found a possible trend in favor of testosterone on the HDRS . Our findings , combined with the conflicting data from earlier smaller studies , suggest that testosterone is not generally effective for depressed men . The possibility remains that testosterone might benefit a particular subgroup of depressed men , but if so , the characteristics of this subgroup would still need to be established Sexual dysfunction , a frequently reported side effect of many antidepressants , may result in patient dissatisfaction and noncompliance with treatment regimens . This paper describes the results of the first placebo-controlled comparison of the efficacy , safety , and effects on sexual functioning of sustained-release bupropion ( bupropion SR ) and the selective serotonin reuptake inhibitor sertraline . This r and omized , double-masked , double-dummy , parallel-group , multicenter trial enrolled 360 patients with moderate-to-severe recurrent major depression . Patients were treated with bupropion SR 150 to 400 mg/d , sertraline 50 to 200 mg/d , or placebo for up to 8 weeks . Patients ' depression and sexual functioning were assessed at weekly or biweekly clinic visits ; safety was assessed by regular monitoring of adverse events , vital signs , and body weight . Treatment groups were similar at baseline in terms of age , sex , and race , and most patients had a diagnosis of moderate uncomplicated depression . Patients treated with bupropion SR or sertraline showed similar improvements on all efficacy measures ; both active treatments were superior to placebo in improving scores on all rating scales for depression at various time points . Significantly more patients treated with sertraline experienced orgasmic dysfunction throughout the study than did patients treated with bupropion SR or placebo ( P < 0.001 ) . Headache was the most frequently reported adverse event in all 3 treatment groups and occurred with similar frequency in each group ( 30 % to 40 % ) . Nausea ( 31 % ) , diarrhea ( 26 % ) , insomnia ( 18 % ) , and somnolence ( 17 % ) occurred in significantly more patients in the sertraline group than in the bupropion SR group ( 18 % , 7 % , 13 % , and 3 % , respectively ) and the placebo group ( 10 % , 11 % , 4 % , and 6 % , respectively ) . Dry mouth occurred more frequently with bupropion SR ( 19 % ) than with sertraline ( 14 % ) or placebo ( 12 % ) , although the differences were not significant . Changes in vital signs were similar in all groups . Similar ( small , but not statistically significant ) decreases in mean body weight were seen in both the bupropion SR ( -1.06 kg ) and sertraline ( -0.79 kg ) groups , whereas the placebo group experienced a minor increase ( 0.21 kg ) . Although bupropion SR and sertraline were similarly well tolerated and effective in the treatment of depression , sertraline treatment was more often associated with sexual dysfunction and certain other adverse events compared with bupropion SR and placebo . Therefore , bupropion SR may be an appropriate choice as an antidepressant for the treatment of sexually active patients & NA ; Sexual side‐effects due to antidepressant treatment are an important consideration when selecting a treatment regimen and can influence patient compliance . Sexual function during treatment with the selective noradrenaline reuptake inhibitor reboxetine , the selective serotonin reuptake inhibitor ( SSRI ) fluoxetine and placebo has been assessed in a multicentre , r and omized , 8‐week , double‐blind study of 450 patients diagnosed with major depressive disorder . Sexual function was measured by the Rush Sexual Inventory completed by male and female patients and administered at baseline , week 4 and week 8 . The results indicate that reboxetine was similar to placebo and superior to fluoxetine in its effect on overall sexual function . There was a greater degree of sexual satisfaction in the reboxetine group compared to fluoxetine ( P = 0.02 ) . The percentage of female patients able to achieve orgasm increased during the study period for women who received reboxetine and placebo , but decreased for those who received fluoxetine . These results suggest that reboxetine may be of particular benefit for patients at risk for sexual dysfunction with SSRIs CONTEXT Sexual dysfunction is a common adverse effect of antidepressants that frequently results in treatment noncompliance . OBJECTIVE To assess the efficacy of sildenafil citrate in men with sexual dysfunction associated with the use of selective and nonselective serotonin reuptake inhibitor ( SRI ) antidepressants . DESIGN , SETTING , AND PATIENTS Prospect i ve , parallel-group , r and omized , double-blind , placebo-controlled trial conducted between November 1 , 2000 , and January 1 , 2001 , at 3 US university medical centers among 90 male out patients ( mean [ SD ] age , 45 [ 8 ] years ) with major depression in remission and sexual dysfunction associated with SRI antidepressant treatment . INTERVENTION Patients were r and omly assigned to take sildenafil ( n = 45 ) or placebo ( n = 45 ) at a flexible dose starting at 50 mg and adjustable to 100 mg before sexual activity for 6 weeks . MAIN OUTCOME MEASURES The primary outcome measure was score on the Clinical Global Impression-Sexual Function ( CGI-SF ) ; secondary measures were scores on the International Index of Erectile Function , Arizona Sexual Experience Scale , Massachusetts General Hospital-Sexual Functioning Question naire , and Hamilton Rating Scale for Depression ( HAM-D ) . RESULTS Among the 90 r and omized patients , 93 % ( 83/89 ) of patients treated per protocol took at least 1 dose of study drug and 85 % ( 76/89 ) completed week 6 end-point assessment s with last observation carried forward analyses . At a CGI-SF score of 2 or lower , 54.5 % ( 24/44 ) of sildenafil compared with 4.4 % ( 2/45 ) of placebo patients were much or very much improved ( P<.001 ) . Erectile function , arousal , ejaculation , orgasm , and overall satisfaction domain measures improved significantly in sildenafil compared with placebo patients . Mean depression scores remained consistent with remission ( HAM-D score < or = 10 ) in both groups for the study duration . CONCLUSION In our study , sildenafil effectively improved erectile function and other aspects of sexual function in men with sexual dysfunction associated with the use of SRI antidepressants . These improvements may allow patients to maintain adherence with effective antidepressant treatment To evaluate the effect of mirtazapine augmentation in patients with sexual dysfunction induced by current selective serotonin reuptake inhibitor ( SSRI ) treatment The aim of this study was to examine the effect of Ginkgo biloba on antidepressant-induced sexual dysfunction . The Ginkgo biloba ( n=19 ) and the placebo groups ( n=18 ) were divided ; each to be administered with Ginkgo biloba and placebo respectively for 2 months by means of a r and omized placebo-controlled , double-blind study . The results of this 2 month trial were : ( 1 ) there was no statistical significant difference from the placebo at weeks 2 , 4 and 8 after medication ; ( 2 ) in comparison with baseline , both the Ginkgo biloba group and the placebo group showed improvement in some part of the sexual function , which is suggestive of the importance of the placebo effect in assessing sexual function . This study did not replicate a prior positive finding supporting the use of Ginkgo biloba for antidepressant , especially SSRI , induced sexual dysfunction Sexual dysfunction is a relatively common side-effect of antidepressants , occurring in approximately one-half of patients , and is associated with significant distress and treatment non-compliance . Dopaminergic agents have been reported to be helpful for the treatment of antidepressant-induced sexual dysfunction and , in this report , we examined the efficacy of the dopamine agonist ropinirole for this indication . Thirteen patients ( three women , 10 men ) , aged 42.6 ± 7.7 years , who reported sexual dysfunction on a stable dose of antidepressant , were treated openly with ropinirole initiated at 0.25 mg/day and titrated up to 2–4 mg/day over 4 weeks , as tolerated . Ten of the 13 took ropinirole for at least 4 weeks , one discontinued due to an adverse event and two because of lack of response . Sexual dysfunction , as assessed by the Arizona Sexual Experience Scale scores , was reduced from 18.8 ± 3.6 to 13.8 ± 4.3 after 4 weeks on ropinirole at a mean dose of 2.1 mg/day . Overall , seven of 13 patients ( 54 % ) were rated as responders on the Clinical Global Impression of Improvement Scale . The addition of ropinirole may represent a potentially useful treatment strategy for antidepressant-induced sexual dysfunction Sexual dysfunction is common during acute and continuation treatment of depressed patients with selective serotonin ( 5-hydroxytryptamine , 5-HT ) re-uptake inhibitors ( ssRIs ) , but there is no consensus on clinical management . Compounds with 5-HT1A agonist properties have been proposed as adjuvant agents in patients continuing with ssRIs . R and omized double-blind placebo-controlled parallel-group fixed-dose 4-week treatment study . Previously depressed male or female patients in symptomatic remission receiving stable doses of fluoxetine or paroxetine but experiencing treatment-emergent sexual dysfunction were r and omised to double-blind treatment with placebo or VML-670 ( a 5-HT1A and 5-HT1D agonist ) . sexual dysfunction was assessed by the Arizona sexual Experiences scale ( ASEX ) . Two-hundred and eighty-eight patients ( 204 women , 84 men ; mean age 44.2 years ) received VML-670 ( n = 149 ; 107 women , 42 men ) or placebo ( n = 139 ; 97 women , 42 men ) . In the intention-to-treat , last-observation carried forward analysis ( n = 282 ) , proportionately more patients became free of sexual dysfunction with VML-670 ( 34.3 % versus 27.9 % with placebo ) but this difference was not statistically significant . Male patients treated with VML-670 showed a significantly greater ( p = 0.01 ) improvement in ability to achieve and maintain penile erection ( a secondary outcome measure ) . A similar proportion of patients reported on-treatment , treatment-emergent adverse events with VML-670 ( 71.1 % ) and placebo ( 68.3 % ) , and a similar proportion experienced at least one treatment-related adverse event ( 36.9 % versus 35.3 % ) . Double-blind treatment with VML-670 offered no significant advantage over placebo on the primary outcome measure in the overall sample . Further studies may be warranted in larger groups of male patients with sexual dysfunction Testosterone replacement is the most effective treatment for sexual dysfunction in hypogonadal men . Comorbid depression and antidepressant side effects may reduce its influence . The authors conducted a 6-week , double-blind , placebo-controlled clinical trial of testosterone gel versus placebo gel in men with major depressive disorder who were currently taking a serotonergic antidepressant and exhibited low or low-normal testosterone level . A total of 100 men were enrolled at 2 study sites ( Boston , Massachusetts , USA , and Tel Aviv , Israel ) . The effects of testosterone augmentation on sexual functioning were determined using domain scores on the International Index of Erectile Function ( IIEF ) . Complete pre- and posttrial IIEF data were available for 63 subjects . Men r and omized to testosterone ( n = 31 ) and placebo ( n = 32 ) were similar in age , baseline testosterone levels , and baseline IIEF scores . At study termination , men r and omized to placebo showed virtually no change from baseline in mean ( 95 % CI ) IIEF score ( −0.7 [ −6.5 , 5.2 ] ) , whereas those receiving testosterone exhibited a substantial increase ( 15.8 [ 8.5 , 23.1 ] ) . The estimated mean difference between groups was 16.8 [ 7.5 , 26.1 ] ; p = .001 by linear regression with adjustment for age and study site . There were also significant between-group differences in each of the 5 IIEF subscales , as well as on the single question involving ejaculatory ability ( p ≤ .03 in all cases ) . Effect sizes in these comparisons remained little changed , and generally remained statistically significant , when we further adjusted for change in depression scores on the Montgomery Asberg Depression Rating Scale . It is notable that the subgroup of men with the highest baseline testosterone levels showed virtually the same improvement as those with lower levels , suggesting that the observed improvement was unlikely to be due simply to correction of hypogonadism alone . In depressed men with low or low-normal testosterone levels who continued to take serotonergic antidepressants , treatment with exogenous testosterone was associated with a significant improvement in sexual function , particularly including ejaculatory ability OBJECTIVE The authors compared low-dose sustained-release bupropion with placebo for sexual dysfunction induced by selective serotonin reuptake inhibitors ( SSRIs ) . METHOD Thirty adults who had received SSRIs for at least 6 weeks , who were euthymic , and who had sexual dysfunction as determined by a total score greater than 19 out of a possible 30 on the Arizona Sexual Experience Scale were r and omly assigned to receive either 150 mg/day of sustained-release bupropion or placebo at 6:00 p.m. for 3 weeks . RESULTS There were no significant differences between the sustained-release bupropion and placebo groups as measured by change in Arizona Sexual Experiences Scale or Hamilton Depression Rating Scale scores or side effects . CONCLUSIONS Future studies should compare higher doses of bupropion for treating sexual dysfunction and should include a greater number of subjects The objective of this study was to determine whether ephedrine , an alpha- and beta-adrenergic agonist previously shown to enhance genital blood flow in women , has beneficial effects in reversing antidepressant-induced sexual dysfunction . Nineteen sexually dysfunctional women receiving either fluoxetine , sertraline , or paroxetine participated in an eight-week , double-blind , placebo-controlled , cross-over study of the effects of ephedrine ( 50 mg ) on self-report measures of sexual desire , arousal , orgasm , and sexual satisfaction . Although there were significant improvements relative to baseline in sexual desire and orgasm intensity/pleasure on 50 mg ephedrine 1-hr prior to sexual activity , significant improvements in these measures , as well as in sexual arousal and orgasmic ability also were noted with placebo . These findings highlight the importance of conducting placebo-controlled trials for this condition |
12,147 | 28,559,865 | Music intervention had a medium overall effect on agitation in dementia , suggesting robust clinical relevance .
While the moderate number of studies does not allow for further differentiation between sub-types of music intervention , the sub-group comparisons indicated promising pathways for future systematic review s. This meta- analysis is the first systematic and quantitative overview supporting clinical ly and statistically robust effects of music intervention on agitation in dementia . | Agitation is a common problem in patients suffering from dementia and encompasses a variety of behaviors such as repetitive acts , restlessness , w and ering , and aggressive behaviors .
Agitation reduces the probability of positive social interaction and increases the psychological and organizational burden .
While medical interventions are common , there is need for complementary or alternative methods .
Music intervention has been brought forward as a promising method to reduce agitation in dementia .
While interventions , target groups and research design s differ , there has so far not been a systematic overview assessing the effect of music intervention for agitation in patients with dementia . | Background : Individuals with dementia often experience poor quality of life ( QOL ) due to behavioral and psychological symptoms of dementia ( BPSD ) . Music therapy can reduce BPSD , but most studies have focused on patients with mild to moderate dementia . We hypothesized that music intervention would have beneficial effects compared with a no-music control condition , and that interactive music intervention would have stronger effects than passive music intervention . Methods : Thirty-nine individuals with severe Alzheimer 's disease were r and omly and blindly assigned to two music intervention groups ( passive or interactive ) and a no-music Control group . Music intervention involved individualized music . Short-term effects were evaluated via emotional response and stress levels measured with the autonomic nerve index and the Faces Scale . Long-term effects were evaluated by BPSD changes using the Behavioral Pathology in Alzheimer 's Disease ( BEHAVE-AD ) Rating Scale . Results : Passive and interactive music interventions caused short-term parasympathetic dominance . Interactive intervention caused the greatest improvement in emotional state . Greater long-term reduction in BPSD was observed following interactive intervention , compared with passive music intervention and a no-music control condition . Conclusion : Music intervention can reduce stress in individuals with severe dementia , with interactive interventions exhibiting the strongest beneficial effects . Since interactive music intervention can restore residual cognitive and emotional function , this approach may be useful for aiding severe dementia patients ’ relationships with others and improving QOL . The registration number of the trial and the name of the trial registry are UMIN000008801 and “ Examination of Effective Nursing Intervention for Music Therapy for Severe Dementia Elderly Person ” respectively Background / Aims : Numerous studies have indicated the value of music therapy in the management of patients with Alzheimer ’s disease . A recent pilot study demonstrated the feasibility and usefulness of a new music therapy technique . The aim of this controlled , r and omised study was to assess the effects of this new music therapy technique on anxiety and depression in patients with mild to moderate Alzheimer-type dementia . Methods : This was a single-centre , comparative , controlled , r and omised study , with blinded assessment of its results . The duration of follow-up was 24 weeks . The treated group ( n = 15 ) participated in weekly sessions of individual , receptive music therapy . The musical style of the session was chosen by the patient . The vali date d ‘ U ’ technique was employed . The control group ( n = 15 ) participated under the same conditions in reading sessions . The principal endpoint , measured at weeks 1 , 4 , 8 , 16 and 24 , was the level of anxiety ( Hamilton Scale ) . Changes in the depression score ( Geriatric Depression Scale ) were also analyzed as a secondary endpoint . Results : Significant improvements in anxiety ( p < 0.01 ) and depression ( p < 0.01 ) were observed in the music therapy group as from week 4 and until week 16 . The effect of music therapy was sustained for up to 8 weeks after the discontinuation of sessions between weeks 16 and 24 ( p < 0.01 ) . Conclusion : These results confirm the valuable effect of music therapy on anxiety and depression in patients with mild to moderate Alzheimer ’s disease . This new music therapy technique is simple to implement and can easily be integrated in a multidisciplinary programme for the management of Alzheimer ’s disease BACKGROUND Music therapy is a potential non-pharmacological treatment for the behavioral and psychological symptoms of dementia , but although some studies have found it to be helpful , most are small and uncontrolled . METHODS This case-control study was carried out by qualified music therapists in two nursing homes and two psychogeriatric wards . The participants were 38 patients with moderate or severe Alzheimer 's disease ( AD ) assigned r and omly to a music therapy group and a control group . RESULTS The study showed a significant reduction in activity disturbances in the music therapy group during a 6-week period measured with the Behavior Pathology in Alzheimer 's Disease Rating Scale ( BEHAVE-AD ) . There was also a significant reduction in the sum of scores of activity disturbances , aggressiveness and anxiety . Other symptoms rated by subscales of the BEHAVE-AD did not decrease significantly . Four weeks later the effects had mostly disappeared . CONCLUSIONS Music therapy is a safe and effective method for treating agitation and anxiety in moderately severe and severe AD . This is in line with the results of some non-controlled studies on music therapy in dementia Objectives : Agitation in nursing home residents with dementia leads to increase in psychotropic medication , decrease in quality of life , and to patient distress and caregiver burden . Music therapy has previously been found effective in treatment of agitation in dementia care but studies have been method ologically insufficient . The aim of this study was to examine the effect of individual music therapy on agitation in persons with moderate/severe dementia living in nursing homes , and to explore its effect on psychotropic medication and quality of life . Method : In a crossover trial , 42 participants with dementia were r and omized to a sequence of six weeks of individual music therapy and six weeks of st and ard care . Outcome measures included agitation , quality of life and medication . Results : Agitation disruptiveness increased during st and ard care and decreased during music therapy . The difference at −6.77 ( 95 % CI ( confidence interval ) : −12.71 , −0.83 ) was significant ( p = 0.027 ) , with a medium effect size ( 0.50 ) . The prescription of psychotropic medication increased significantly more often during st and ard care than during music therapy ( p = 0.02 ) . Conclusion : This study shows that six weeks of music therapy reduces agitation disruptiveness and prevents medication increases in people with dementia . The positive trends in relation to agitation frequency and quality of life call for further research with a larger sample Background Agitated behavior is a widespread problem that adversely affects the health of nursing home residents and increases the cost of their care . Objective To examine whether modifying environmental stimuli by the use of calming music and h and massage affects agitated behavior in persons with dementia . Method A four group , repeated measures experimental design was used to test the effect of a 10-minute exposure to either calming music , h and massage , or calming music and h and massage simultaneously , or no intervention ( control ) on the frequency and type of agitated behaviors in nursing home residents with dementia ( N = 68 ) . A modified version of the Cohen-Mansfield Agitation Inventory was used to record agitated behaviors . Results Each of the experimental interventions reduced agitation more than no intervention . The benefit was sustained and increased up to one hour following the intervention ( F = 6.47 , p < .01 ) . The increase in benefit over time was similar for each intervention group . When types of agitated behaviors were examined separately , none of the interventions significantly reduced physically aggressive behaviors ( F = 1.93 , p = .09 ) , while physically nonaggressive behaviors decreased during each of the interventions ( F = 3.78 , p < 01 ) . No additive benefit result ed from simultaneous exposure to calming music and h and massage . At one hour following any intervention , verbally agitated behavior decreased more than no intervention . Conclusion Calming music and h and massage alter the immediate environment of agitated nursing home residents to a calm structured surrounding , off setting disturbing stimuli , but no additive benefit was found by combining interventions simultaneously We undertook a r and omised controlled trial to assess whether a music therapy ( MT ) scheme of administration , including three working cycles of one month spaced out by one month of no treatment , is effective to reduce behavioural disturbances in severely demented patients . Sixty persons with severe dementia ( 30 in the experimental and 30 in the control group ) were enrolled . Baseline multidimensional assessment included demographics , Mini Mental State Examination ( MMSE ) , Barthel Index and Neuropsychiatry Inventory ( NPI ) for all patients . All the patients of the experimental and control groups received st and ard care ( educational and entertainment activities ) . In addition , the experimental group received three cycles of 12 active MT sessions each , three times a week . Each 30-min session included a group of three patients . Every cycle of treatment was followed by one month of wash-out . At the end of this study , MT treatment result ed to be more effective than st and ard care to reduce behavioural disorders . We observed a significant reduction over time in the NPI global scores in both groups ( F 7,357 = 9.06 , p < 0.001 ) and a significant difference between groups ( F 1,51 = 4.84 , p < 0.05 ) due to a higher reduction of behavioural disturbances in the experimental group at the end of the treatment ( Cohen 's d = 0.63 ) . The analysis of single NPI items shows that delusions , agitation and apathy significantly improved in the experimental , but not in the control group . This study suggests the effectiveness of MT approach with working cycles in reducing behavioural disorders of severely demented patients Background Music therapy ( MT ) has been proposed as valid approach for behavioral and psychologic symptoms ( BPSD ) of dementia . However , studies demonstrating the effectiveness of this approach are lacking . Objective To assess MT effectiveness in reducing BPSD in subjects with dementia . Method Fifty-nine persons with dementia were enrolled in this study . All of them underwent a multidimensional assessment including Mini Mental State Examination , Barthel Index and Neuropsychiatry Inventory at enrolment and after 8 , 16 , and 20 weeks . Subjects were r and omly assigned to experimental ( n=30 ) or control ( n=29 ) group . The MT sessions were evaluated with st and ardized criteria . The experimental group received 30 MT sessions ( 16 wk of treatment ) , whereas the control group received educational support or entertainment activities . Results NPI total score significantly decreased in the experimental group at 8th , 16th , and 20th weeks ( interaction time × group : F3 , 165=5.06 , P=0.002 ) . Specific BPSD ( ie , delusions , agitation , anxiety , apathy , irritability , aberrant motor activity , and night-time disturbances ) significantly improved . The empathetic relationship and the patients ' active participation in the MT approach , also improved in the experimental group . Conclusions The study shows that MT is effective to reduce BPSD in patients with moderate-severe dementia BACKGROUND Agitated behaviours are identified by caregivers as the most challenging in dementia care . Alternative approaches reducing occurrence of agitated behaviours and the need for chemical or physical restraints become valuable for institutionalized elders with dementia . OBJECTIVE AND SETTING This study was to evaluate the effects of group music with movement intervention on occurrence of agitated behaviours of institutionalized elders with dementia in Taiwan . METHODS A r and omized controlled trial was used . Thirty-six institutionalized elders with dementia completed the study , with 18 in the experimental group receiving group music with movement intervention twice a week for 4 weeks and 18 in the control group receiving usual care without intervention . Modified Cohen-Mansfield Agitation Inventory was used to assess agitated behaviours at baseline , weeks 2 and 4 . RESULTS Agitated behaviours were significantly reduced in the experimental group following 4 weeks of group music with movement intervention compared to that of the control group ( p<0.001 ) . CONCLUSIONS Group music with movement intervention can be beneficial in managing agitated behaviours of those with dementia and should be incorporated into care routines in residential facilities OBJECTIVE This experimental study aim ed to evaluate the effects of a group music intervention on anxiety and agitation of institutionalized older adults with dementia . METHODS A total of 60 participants were r and omly assigned to an experimental or a control group . The experimental group received a 30-min music intervention using percussion instruments with familiar music in a group setting in mid afternoon twice weekly for 6 weeks , whereas the control group received usual care with no music intervention . The Rating of Anxiety in Dementia scale was used to assess anxiety , and Cohen-Mansfield Agitation Inventory was used to assess agitation at baseline , week 4 and week 6 . RESULTS Repeated measures analysis of covariance indicated that older adults who received a group music intervention had a significantly lower anxiety score than those in the control group while controlling for pre-test score and cognitive level ( F = 8.98 , p = 0.004 ) . However , the reduction of agitation between two groups was not significantly different . CONCLUSIONS Anxiety and agitation are common in older adults with dementia and have been reported by caregivers as challenging care problems . An innovative group music intervention using percussion instruments with familiar music as a cost-effective approach has the potential to reduce anxiety and improve psychological well-being of those with dementia In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies The purpose of this study was to examine the effects of recorded , preferred music in decreasing occurrences of aggressive behavior among individuals with Alzheimer 's type dementia during bathing episodes . Eighteen older adults , age 55 to 95 , with severe levels of cognitive impairment , participated in the study . They were r and omly scheduled for observation during bath time under either a control ( no music ) condition or an experimental condition in which recorded selection s of preferred music were played via audiotape recorder during the bathing episode . Following a 2-week ( 10 episode ) observation period , conditions were reversed . A total of 20 observations were recorded for each individual . Results indicated that during the music condition , decreases occurred in 12 of 15 identified aggressive behaviors . Decreases were significant ( p < 0.05 ) for the total number of observed behaviors and for hitting behaviors . During the music condition , caregivers frequently reported improved affect and a general increase in cooperation with the bathing task . The implication s of these findings for improving the overall quality of care for severely cognitively impaired older adults are discussed OBJECTIVES To assess the effects of active music therapy ( MT ) and individualized listening to music ( LtM ) on behavioral and psychological symptoms of dementia ( BPSDs ) in persons with dementia ( PWDs ) . DESIGN R and omized controlled trial . SETTING Nine Italian institutions . PARTICIPANTS Persons with moderate to severe dementia and BPSDs ( N = 120 ) were r and omized to one of three treatments . INTERVENTIONS All groups received st and ard care ( SC ) , and two groups attended 20 individualized MT or LtM sessions , twice a week , in addition to SC . MEASUREMENTS The Neuropsychiatric Inventory ( NPI ) , Cornell Scale for Depression in Dementia ( CSDD ) , and Cornell-Brown Scale for Quality of Life in Dementia ( CBS-QoL ) were administered before treatment , after treatment , and at follow-up to evaluate behavioral and psychological outcomes . A specific coding scheme ( Music Therapy Check List-Dementia ) was used to evaluate the MT process . RESULTS Behavioral assessment did not show significant differences between groups . All groups showed a reduction over time in NPI global score ( P ≤ .001 ) , CSDD ( P = .001 ) , and CBS-QoL ( P = .01 ) . The NPI global score fell 28 % in the MT group , 12 % in the LtM group , and 21 % in the SC group at the end of treatment . An exploratory post hoc analysis showed similar within-group improvements for the NPI Delusion , Anxiety , and Disinhibition subscales . In the MT group , communication and relationships between the music therapists and PWDs showed a positive albeit nonsignificant trend during treatment . CONCLUSION The addition of MT or LtM to st and ard care did not have a significant effect on BPSDs in PWDs . Further studies on the effects of the integration of st and ard care with different types of music interventions on BPSD in PWD are warranted Limited information is available regarding the incidence , nature , and treatment of behavioral problems in Alzheimer 's disease ( AD ) . A chart review of 57 out patients with a diagnosis of AD was conducted to examine these issues . Thirty-three ( 58 % ) patients had significant behavioral symptomatology ( most commonly delusions , nonspecific agitation , and diurnal rhythm disturbances ) . Twenty-seven were treated with thioridazine ( 10 - 250 mg/day ) , 15 ( 55.6 % ) of whom were judged to have a positive response ( mean maximum dose = 55 mg/day ) . Information regarding the characteristic phenomenology of the behavioral symptoms studied was used to design a clinical rating instrument for AD patients , the Behavioral Pathology in Alzheimer 's Disease Rating Scale ( BEHAVE-AD ) , which should be useful in prospect i ve studies of behavioral symptoms as well as in pharmacologic trials |
12,148 | 27,783,051 | Despite insufficient evidence to draw a conclusion , our results suggest that use of NPIs as adjunctive treatments , specifically non-exercise interventions , may affect positively serum or plasma BDNF in patients with schizophrenia | Several studies have investigated the relationship between non-pharmacological interventions ( NPIs ) and peripheral brain-derived neurotrophic factor ( BDNF ) in schizophrenia patients .
We conducted a systematic review and meta- analysis to review the efficacy of NPIs on peripheral serum and plasma BDNF in subjects with schizophrenia ( including schizoaffective disorder ) . | Publication bias , sometimes known as the " file-drawer problem " or " funnel-plot asymmetry , " is common in empirical research . The authors review the implication s of publication bias for quantitative research synthesis ( meta- analysis ) and describe existing techniques for detecting and correcting it . A new approach is proposed that is suitable for application to meta-analytic data sets that are too small for the application of existing methods . The model estimates parameters relevant to fixed-effects , mixed-effects or r and om-effects meta- analysis contingent on a hypothetical pattern of bias that is fixed independently of the data . The authors illustrate this approach for sensitivity analysis using 3 data sets adapted from a commonly cited reference work on research synthesis ( H. M. Cooper & L. V. Hedges , 1994 ) Impairments of attention and memory are evident in early psychosis , and are associated with functional disability . In a group of stable , medicated women patients , we aim ed to determine whether participating in aerobic exercise or yoga improved cognitive impairments and clinical symptoms . A total of 140 female patients were recruited , and 124 received the allocated intervention in a r and omized controlled study of 12 weeks of yoga or aerobic exercise compared with a waitlist group . The primary outcomes were cognitive functions including memory and attention . Secondary outcome measures were the severity of psychotic and depressive symptoms , and hippocampal volume . Data from 124 patients were included in the final analysis based on the intention-to-treat principle . Both yoga and aerobic exercise groups demonstrated significant improvements in working memory ( P<0.01 ) with moderate to large effect sizes compared with the waitlist control group . The yoga group showed additional benefits in verbal acquisition ( P<0.01 ) and attention ( P=0.01 ) . Both types of exercise improved overall and depressive symptoms ( all P⩽0.01 ) after 12 weeks . Small increases in hippocampal volume were observed in the aerobic exercise group compared with waitlist ( P=0.01 ) . Both types of exercise improved working memory in early psychosis patients , with yoga having a larger effect on verbal acquisition and attention than aerobic exercise . The application of yoga and aerobic exercise as adjunctive treatments for early psychosis merits serious consideration . This study was supported by the Small Research Funding of the University of Hong Kong ( 201007176229 ) , and RGC funding ( C00240/762412 ) by the Authority of Research , Hong Kong IMPORTANCE More effective treatments are needed for negative symptoms of schizophrenia , which are typically chronic , disabling , and costly . Negative symptoms have previously been associated with reduced blood folate levels , especially among patients with low-functioning variants in genes that regulate folate metabolism , suggesting the potential utility of folate supplementation . OBJECTIVES To determine whether folic acid plus vitamin B12 supplementation reduces negative symptoms of schizophrenia and whether functional variants in folate-related genes influence treatment response . DESIGN Parallel-group , r and omized , double-blind , placebo-controlled clinical trial of 16 weeks of treatment with 2 mg of folic acid and 400 μg of vitamin B12 . SETTING Three community mental health centers affiliated with academic medical centers in the United States . PARTICIPANTS Out patients with chronic schizophrenia who were psychiatrically stable but displayed persistent symptoms despite antipsychotic treatment . Eligible patients were 18 to 68 years old , were treated with an antipsychotic agent for 6 months or more at a stable dose for 6 weeks or more , and scored 60 or more on the Positive and Negative Syndrome Scale . INTERVENTION One hundred forty subjects were r and omized to receive daily oral folic acid plus vitamin B12 or placebo . MAIN OUTCOME MEASURES Change in negative symptoms ( Scale for the Assessment of Negative Symptoms [ SANS ] ) , as well as positive and total symptoms ( Positive and Negative Syndrome Scale ) . RESULTS Folate plus vitamin B12 improved negative symptoms significantly compared with placebo ( group difference , -0.33 change in SANS score per week ; 95 % CI , -0.62 to -0.05 ) when genotype was taken into account but not when genotype was excluded . An interaction of the 484C > T variant of FOLH1 ( rs202676 ) with treatment was observed ( P = .02 ) , where only patients homozygous for the 484 T allele demonstrated significantly greater benefit with active treatment ( -0.59 change in SANS score per week ; 95 % CI , -0.99 to -0.18 ) . In parallel , we observed an inverse relationship between red blood cell folate concentration at baseline and 484C allele load ( P = .03 ) , which persisted until 8 weeks of treatment . Change in positive and total symptoms did not differ between treatment groups . CONCLUSIONS Folate plus vitamin B12 supplementation can improve negative symptoms of schizophrenia , but treatment response is influenced by genetic variation in folate absorption . These findings support a personalized medicine approach for the treatment of negative symptoms . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00611806 Varenicline , alpha4beta2 nicotinic acetylcholine receptor ( nAChR ) partial agonist , is a new class of medications for treating nicotine dependence . As an alpha4beta2 nAChR partial agonist , varenicline serves to reduce nicotine withdrawal symptoms , while high-affinity binding of the agonist mitigates the reinforcing effects of smoking . In the present study , we compared serum brain-derived neurotrophic factor ( BDNF ) levels of nicotine dependence and nonsmokers , and we investigated changes in serum BDNF levels after 8 weeks of treatment with varenicline . Patients met the DSM-IV criteria for nicotine dependence . Both the Fagerström test for nicotine dependence ( FTND ) and the Tobacco Dependence Screener ( TDS ) were used . Serum BDNF levels and breath carbon monoxide ( CO ) levels were measured before and 8 weeks after varenicline treatment . Fourteen of 16 subjects ( 87.5 % ) stopped smoking within 12 weeks of varenicline treatment . Thirteen healthy nonsmokers who never had previously smoked were r and omly selected as a control group . Serum BDNF levels of patients before treatment ( 4.8 + /- 3.8 ng/ml ) were significantly lower than those in the control group ( 12.4 + /- 6.13 ng/ml ) . Serum BDNF levels had not increased from baseline ( 4.8 + /- 3.8 ng/ml ) to 8 weeks after varenicline treatment ( 3.0 + /- 1.1 ng/ml ) of patients . These results suggest that smoking might decrease serum BDNF levels and that treatment with varenicline for 8 weeks , combined with 12 weeks of not smoking , does not increase serum BDNF levels in smokers OBJECTIVE To examine the effects of Hatha yoga therapy on resilience , brain-derived neurotrophic factor ( BDNF ) levels , and salivary alpha amylase ( SAA ) activity in patients with schizophrenia-spectrum disorders . DESIGN AND PARTICIPANTS Single-blinded , r and omized controlled study in which out patients with schizophrenia or related psychotic disorders ( according to International Classification of Diseases , 10th Revision ) were r and omly assigned to a yoga or a control group . SETTING November 2012-April 2013 at Yamanashi Prefectural Kita Hospital , Japan . INTERVENTIONS In the yoga group , patients received weekly 1-hour Hatha yoga sessions , in addition to regular treatment , for 8 weeks . Those in the control group underwent regular treatment , which included a daycare rehabilitation program . OUTCOME MEASURES Assessment s included the 25-item Resilience Scale ( RS ) , Positive and Negative Syndrome Scale ( PANSS ) , plasma and salivary BDNF level , and SAA activity . RESULTS Fifty patients participated ( 25 in each group ; mean age±st and ard deviation , 50.9±11.3 years ; mean duration of illness , 25.0±10.3 years ; mean total PANSS score , 78.2±17.3 ) . No significant differences in changes in any variable from baseline to week 8 were found between the two groups ( changes in the yoga group versus the control group : RS score , -1.6±19.9 versus 0.3±17.2 ; PANSS score , 0.5±12.0 versus 5.0±15.6 ; plasma BDNF , 41.6±377.0 pg/dl versus 73.4±346.0 pg/dl ; SAA , -26.2±72.6 kU/l versus -13.8±68.0 kU/l , respectively ) . CONCLUSIONS Adjunct yoga therapy showed no positive changes in resilience level or stress markers . Duration and intensity of yoga sessions and the focus on patients with chronic illness may explain the negative observations in light of past positive evidence regarding yoga therapy 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 Objectives : l-Theanine ( & ggr;-glutamylethylamide ) augmentation to antipsychotic therapy ameliorates positive , activation , and anxiety symptoms in schizophrenia and schizoaffective disorder patients . This study examines the association between circulating levels of neurochemical indicators and the beneficial clinical effects of l-theanine augmentation . Methods : Serum levels of neurochemical indicators such as brain-derived neurotrophic factor ( BDNF ) , dehydroepi and rosterone ( DHEA ) , its sulfate ( DHEAS ) , cortisol , cholesterol , and insulin were monitored in 40 schizophrenia and schizoaffective disorder patients during an 8-week , double-blind , r and omized , placebo-controlled trial with l-theanine ( 400 mg/d ) . Multiple regression analysis was applied for search ing association between improvement in symptom scores and changes in circulating levels of neurochemical indicators for an 8-week trial . Results : Regression models among l-theanine-treated patients indicate that circulating levels of BDNF and cortisol-to-DHEAS*100 molar ratio were significantly associated with the beneficial clinical effects of l-theanine augmentation . Variability of serum BDNF levels accounted for 26.2 % of the total variance in reduction of dysphoric mood and 38.2 % in anxiety scores . In addition , the changes in cortisol-to-DHEAS*100 molar ratio accounted for 30 % to 34 % of the variance in activation factor and dysphoric mood scores and for 15.9 % in anxiety scores . Regression models among placebo-treated patients did not reach significant level . Conclusions : These preliminary results indicate that circulating BDNF and cortisol-to-DHEAS*100 molar ratio may be involved in the beneficial clinical effects of l-theanine as augmentation of antipsychotic therapy in schizophrenia and schizoaffective disorder patients There is evidence that major psychiatric discords such as schizophrenia ( SZ ) and bipolar disorder ( BD ) are associated with dysregulation of synaptic plasticity with downstream alterations of neurotrophins . Brain-derived neurotrophic factor ( BDNF ) is the most widely distributed neurotrophin in the central nervous system ( CNS ) , and performs many biological functions such as promoting the survival , differentiation , and plasticity of neurons . Variants in the BDNF gene increase the risk of SZ and bipolar disorder . Chronic administration of drugs used to treat SZ and BD , such as lithium , valproate , quetiapine , clozapine , and olanzapine , increases BDNF expression in rat brain . To examine serum BDNF , three groups of chronically medicated DSM-IV SZ patients , on treatment with clozapine ( n=27 ) , typical ( n=14 ) , and other atypical antipsychotics ( n=19 ) , 30 euthymic BD patients , and 26 healthy control had 5 ml blood sample s collected by venipuncture . Serum BDNF levels were significantly higher in SZ patients ( p<0.001 ) when compared to either controls or euthymic BD patients . Increased BDNF in SZ patients might be related to the course of illness or to treatment variables . Prospect i ve studies are warranted Some pre clinical and postmortem studies suggest that the effects of atypical antipsychotics could be mediated by brain-derived neurotrophic factor ( BDNF ) . Olanzapine is an atypical antipsychotic with shown efficacy in psychosis treatment . The aim of this study was to compare plasma BDNF levels at baseline and after 1 year of olanzapine treatment in 18 drug-naive patients who experienced a first psychotic episode with those of 18 healthy control participants matched by age , sex , and socioeconomic level . Plasma BDNF levels were measured in patients at the index episode and at 1 , 6 , and 12 months of follow-up using an enzyme-linked immunosorbent assay . Symptoms and functioning of patients and controls were assessed with the Positive and Negative Symptom Scale and Global Assessment of Function Scale . BDNF levels of patients at onset were significantly lower than controls but increased toward control values during olanzapine treatment . There was a significant positive correlation between BDNF levels and functioning ( Global Assessment of Function Scale ) . BDNF levels were also negatively correlated with positive symptoms , but not with negative symptoms or general psychopathology . Results suggest that olanzapine can offset the low BDNF levels at the onset of first psychotic episodes , and improving psychotic symptoms . The increase in BDNF levels may be its mechanism of action in improving positive symptoms Introduction : Brain-derived neurotrophic factor ( BDNF ) is not only involved in the development , differentiation , and survival of dopaminergic neurons ; it also regulates fast neurotransmission and neuronal activity . Methods : In this study , 22 patients with acute schizophrenia and 22 age-matched healthy volunteers were recruited , and BDNF serum concentrations were measured in unmedicated patients and after 2 weeks and 4 weeks of medication . Results : Brain-derived neurotrophic factor serum levels of unmedicated schizophrenic patients ( n = 22 ; 4.38 ± 2.1 ng/mL ) were significantly decreased compared to the age-matched healthy volunteers ( n = 44 , df = 42 , P = 0.029 ) . In a mixed-model repeated- measures analysis of variance , a significant BDNF increase has been found during treatment ( & khgr;2 = 2.91 ; df = 1 ; P < 0.0001 ) . The percental change of BDNF ( increase , 173 % ± 110 ) correlated negatively with the percental change of PANSS score ( decrease : 75 % ± 22 ; n = 18 ; r = −0.554 ; P = 0.032 ) . Conclusions : Our study replicates studies showing that unmedicated patients with schizophrenia have decreased serum BDNF levels compared with healthy controls . Brain-derived neurotrophic factor increase during treatment seems to parallel positive and negative symptom improvement OBJECTIVE To examine the effectiveness of group mindfulness-based intervention ( MBI ) in patients diagnosed with severe mental illness . The primary outcome was health-related psychological quality of life . Secondary measures were environmental , social and physical health related quality of life , frequency and intensity of psychotic symptoms and daily-life mindfulness . METHOD Forty-four patients from a public community rehabilitation center for people with severe mental illness were recruited , and r and omly allocated to Integrated Rehabilitation Treatment ( IRT ) or IRT plus MBI . Measures included PANSS interview , WHOQOL-BREF , and Mindfulness Attention Awareness Scale . MBI comprised 26 one-hour weekly sessions . Intention-to-treat analysis was used . RESULTS One patient did not complete IRT+MBI and two did not complete IRT . At baseline there were no statistical group differences in demographic characteristics or primary and secondary outcomes . At post-treatment interaction between treatment and time in health-related psychological quality of life was statistically significant , and simple effect analysis showed significant differences for between and within subject factor in favor of MBI . Interaction was also significant in PANSS negative symptoms , simple effects showed a statistical trend in within subject factor . Time factor was significant in environmental and physical quality of life . CONCLUSIONS Data suggest mindfulness added to IRT may enhance psychological quality of life in people with severe mental illness from a public community center . Results also suggest that mindfulness may impact frequency and intensity of negative symptoms Background : Schizophrenia is a highly disabling illness . Previous studies have shown yoga to be a feasible add-on therapy in schizophrenia . Aims : The current study aim ed to test the efficacy of yoga as an add-on treatment in out patients with schizophrenia . Setting s and Design : The study done at a tertiary psychiatry center used a single blind r and omized controlled design with active control and waitlist groups . Material s and Methods : Consenting patients with schizophrenia were r and omized into yoga , exercise , or waitlist group . They continued to receive pharmacological therapy that was unchanged during the study . Patients in the yoga or exercise group were offered supervised daily procedures for one month . All patients were assessed by a blind rater at the start of the intervention and at the end of 4 months . Results : Kendall tau , a nonparametric statistical test , showed that significantly more patients in the yoga group improved in Positive and Negative Syndrome Scale ( PANSS ) negative and total PANSS scores as well as social functioning scores compared with the exercise and waitlist group . Odds ratio analysis showed that the likelihood of improvement in yoga group in terms of negative symptoms was about five times greater than either the exercise or waitlist groups . Conclusion : In schizophrenia patients with several years of illness and on stabilized pharmacological therapy , one-month training followed by three months of home practice s of yoga as an add-on treatment offered significant advantage over exercise or treatment as usual . Yoga holds promise as a complementary intervention in the management of schizophrenia Support for prospect i ve registration of protocol s for systematic review s has been gathering momentum . The PRISMA statement , a guideline for reporting systematic review s and meta-analyses of studies that evaluate health-care interventions , advocates registration . Well-conducted systematic review s are accepted as the best- quality evidence to inform policy and practice , and the dramatic upward trend in the number of systematic review s published annually ( fi gure ) is set to continue . However , there is currently no single facility for identifying this type of research in advance of the appearance of the results of the review . There is concern about and evidence of publication and selective outcome -reporting biases associated with systematic review s. An open registry of review s captured at the protocol stage would facilitate good practice in systematic review s by providing transparency of the review process and outcomes . Discrepancies between the methods of the published review and those planned in the registered protocol could be more readily identifi ed . Registration might also encourage full publication of the review ’s fi ndings and transparency in changes to methods that could bias fi ndings . In both the prevention and revelation of potential bias , registration should improve quality and increase confi dence that policy or practice informed by the fi ndings of systematic review s are indeed drawing on best- quality evidence . A registry of protocol s of systematic review s could assist those planning new review s and updating existing ones . Easy access to information about ongoing review s should help to optimise the use of fi nite re sources by enabling funding and commissioning agencies to avoid unnecessary duplication and encourage collaboration . A comprehensive registry could also create opportunities for method ological and other research , both within and across disciplines . Existing access to systematic - review protocol s is limited to the outputs of individual organisations , such as the Cochrane and Campbell Collaborations and the Joanna Briggs Institute . The National Public Health Service for Wales is piloting an All Wales Systematic Review s Register , but , up to now , there has been no central ised comprehensive registry of systematic - review protocol s. We are developing an international facility to register the details of ongoing systematic review s in health and social care . Our registry is being established with the existing platform and infrastructure that supports the Data base of Abstract s of Review s of Eff ects ( DARE ) , the NHS Economic Evaluations Data base ( NHS EED ) and the Health Technology Assessment ( HTA ) data base produced by the Centre for Review s and Dissemination . The initial scope of the registry will be limited to systematic review s of the eff ectiveness of health interventions . However , the longterm aim is for the registry to include details of all ongoing systematic review s with a health-related outcome in the broadest sense . Ultimately , inclusion will encompass systematic review s of health-care interventions , and review s of the social determinants of health , of service delivery , and of risk factors and genetic associations . Our web-based registry will off er free public access , be electronically search able , and open to all prospect i ve registrants . Registration will require the provision of a minimum data set , the completeness of which will be checked automatically before registration . After acceptance , the registry ’s entry and protocol for the review , if available , will be loaded on the data base as a permanent entry and a unique identifi cation number issued . An audit trail for any amendments to the information will be available within the record . Links to result ing publications will be added . These provisions ensure that the registry will match the relevant criteria required of clinical trials registries Brain-derived neurotrophic factor ( BDNF ) has been suggested to be involved in the etiology of schizophrenia . There is a line of evidence that disruption of neurotrophins could play a role in the etiology of schizophrenia , and antipsychotics show their effect by altering levels of neurotrophins . The aim of this study was to evaluate the effect of antipsychotics on serum BDNF levels and their relationship with the symptoms in patients with schizophrenia . Twenty-two schizophrenia patients were enrolled in the study . The control group consisted of 22 age- and sex-matched physically and mentally healthy volunteers ( 7 male , 15 female ) . Serum BDNF levels and the positive and negative syndrome scale ( PANSS ) scores were recorded at baseline and after 6 weeks of treatment . Serum BDNF levels were also recorded in the control group . Schizophrenia patients who failed to meet 30 % improvement in PANSS score were excluded from the study . The baseline serum BDNF levels of schizophrenia patients were lower than those of controls ( t = 4.56 ; df = 21 ; p < 0.001 ) . There was no correlation between serum BDNF levels and PANSS scores in patients with schizophrenia ( p > 0.05 ) . Although PANSS ( for positive symptoms p < 0.001 , for negative symptoms p < 0.001 ) and general psychopathology ( t = 20.9 ; df = 22 ; p < 0.001 ) scores improved significantly after 6 weeks of antipsychotic treatment ; there was no change in BDNF levels in patients ' serum ( p > 0.05 ) . Our results support the view that BDNF would be associated with schizophrenia . However , we could not conclude that treatment with antipsychotics alters serum BDNF levels in patients with schizophrenia BACKGROUND Brain-derived neurotrophic factor ( BDNF ) plays a critical role in neurodevelopment and plasticity ; decreased BDNF functioning may contribute to the pathogenesis of schizophrenia . However , BDNF levels are not static ; in animal experiments , brain BDNF increases during spatial learning , and in clinical depression , successful antidepressant treatment raises serum BDNF . We asked : would neuroplasticity-based cognitive training in schizophrenia result in increased serum BDNF ? METHODS Fifty-six schizophrenia out patients and 16 matched healthy comparison subjects were assessed on baseline cognitive performance and serum BDNF . Schizophrenia subjects were r and omly assigned to either 50 hours ( 10 weeks ) of computerized auditory training or a computer game control condition , followed by re assessment of cognition and serum BDNF . RESULTS At baseline , schizophrenia participants had significantly lower-than-normal serum BDNF . Schizophrenia subjects who engaged in computerized cognitive training design ed to improve auditory processing showed significant cognitive gains and a significant increase in serum BDNF compared with subjects who played computer games . This increase was evident after 2 weeks of training , and after 10 weeks in the active condition , subjects " normalized " their mean serum BDNF levels , whereas the control group showed no change . In the active condition , change in BDNF was significantly associated with improved quality of life . CONCLUSIONS Serum BDNF levels are significantly increased in clinical ly stable , chronically ill schizophrenia subjects after neuroplasticity-based cognitive training , but not after computer games . Serum BDNF levels may serve as a peripheral biomarker for the effects of intensive cognitive training and may provide a useful tool for the evaluation of cognitive enhancement methods in schizophrenia Individuals with schizophrenia display substantial neurocognitive deficits for which available treatments offer only limited benefits . Yet , findings from studies of animals , clinical and non clinical population s have linked neurocognitive improvements to increases in aerobic fitness ( AF ) via aerobic exercise training ( AE ) . Such improvements have been attributed to up-regulation of brain-derived neurotrophic factor ( BDNF ) . However , the impact of AE on neurocognition , and the putative role of BDNF , have not been investigated in schizophrenia . Employing a proof-of-concept , single-blind , r and omized clinical trial design , 33 individuals with schizophrenia were r and omized to receive st and ard psychiatric treatment ( n = 17 ; " treatment as usual " ; TAU ) or attend a 12-week AE program ( n = 16 ) utilizing active-play video games ( Xbox 360 Kinect ) and traditional AE equipment . Participants completed assessment s of AF ( indexed by VO2 peak ml/kg/min ) , neurocognition ( MATRICS Consensus Cognitive Battery ) , and serum-BDNF before and after and 12-week period . Twenty-six participants ( 79 % ) completed the study . At follow-up , the AE participants improved their AF by 18.0 % vs a -0.5 % decline in the TAU group ( P = .002 ) and improved their neurocognition by 15.1 % vs -2.0 % decline in the TAU group ( P = .031 ) . Hierarchical multiple regression analyses indicated that enhancement in AF and increases in BDNF predicted 25.4 % and 14.6 % of the neurocognitive improvement variance , respectively . The results indicate AE is effective in enhancing neurocognitive functioning in people with schizophrenia and provide preliminary support for the impact of AE-related BDNF up-regulation on neurocognition in this population . Poor AF represents a modifiable risk factor for neurocognitive dysfunction in schizophrenia for which AE training offer a safe , nonstigmatizing , and side-effect-free intervention Short-term clinical trials of omega-3 polyunsaturated fatty acids ( n-3 PUFA ) as add-on therapy in patients with schizophrenia revealed mixed results . The majority of these studies used an 8- to 12-week intervention based on ethyl-eicosapentaenoic acid . A r and omized placebo-controlled trial was design ed to compare the efficacy of 26-week intervention , composed of either 2.2 g/day of n-3 PUFA , or olive oil placebo , with regard to symptom severity in first-episode schizophrenia patients . Seventy-one patients ( aged 16 - 35 ) were enrolled in the study and r and omly assigned to the study arms . The primary outcome measure of the clinical evaluation was schizophrenia symptom severity change measured by the Positive and Negative Syndrome Scale ( PANSS ) . Mixed models repeated measures analysis revealed significant differences between the study arms regarding total PANSS score change favouring n-3 PUFA ( p = 0.016 ; effect size ( ES ) = 0.29 ) . A fifty-percent improvement in symptom severity was achieved significantly more frequently in the n-3 PUFA group than in the placebo group ( 69.4 vs 40.0 % ; p = 0.017 ) . N-3 PUFA intervention was also associated with an improvement in general psychopathology , measured by means of PANSS ( p = 0.009 ; ES = 0.32 ) , depressive symptoms ( p = 0.006 ; ES = 0.34 ) , the level of functioning ( p = 0.01 ; ES = 0.31 ) and clinical global impression ( p = 0.046 ; ES = 0.29 ) . The findings suggest that 6-month intervention with n-3 PUFA may be a valuable add-on therapy able to decrease the intensity of symptoms and improve the level of functioning in first-episode schizophrenia patients |
12,149 | 29,351,510 | In conclusion , in adults with SAPS , scapular focused interventions can improve short-term shoulder pain and function | The relationship between subacromial pain syndrome ( SAPS ) and altered scapular movement has been previously reported .
The purpose of this review was to determine the effect of interventions that focus on addressing scapular components to improve shoulder pain , function , shoulder range of motion ( ROM ) , and muscle strength in adults with SAPS . | The aim of this study was to compare the recruitment patterns and latencies of the scapular muscles , as well as the isokinetic performance of the shoulder rotators in 10 subjects with unilateral impingement syndrome who comprised the impingement group ( IG ) with a control group ( CG ) of 10 asymptomatic subjects . The recruitment patterns and latencies were evaluated by electromyographic activity during arm elevation in the scapular plane . Isokinetic work ratios of the shoulder rotator muscles were used to analyze muscular performance . A 2 x 2 ANOVA detected that muscular performance and recruitment patterns were similar for both groups and sides . However , the ANOVA revealed a significant side and group interaction , indicating that the scapular muscle latencies of the affected shoulder was greater than that of the nonaffected side only for the IG ( p < .001 ) . These findings indicated that subjects with light to moderate impingement syndrome showed late recruitment of the scapular muscles during arm elevation . However , muscular performance of the shoulder rotator muscles was not affected BACKGROUND AND PURPOSE Exercise therapy is a commonly used conservative therapy for long-term subacromial pain . However , there is no consensus regarding what type of exercises and dosage is most effective . The aim of this study was to compare the effect of two exercise programmes : 1 ) high-dosage ( HD ) medical exercise therapy versus 2 ) low-dosage ( LD ) exercise therapy programme for subjects with long-term subacromial pain . METHODS This study used a r and omized , controlled clinical trial with an intention-to-treat analysis . Sixty-one subjects were r and omly assigned by concealment either to an HD medical exercise therapy group ( n = 31 ) or to an LD exercise therapy group ( n = 30 ) . Pain ( visual analogue scale [ VAS ] ) and function ( Shoulder Rating Question naire [ SRQ ] ) were measured at inclusion , at end of treatment and at 6 and 12 months follow-up . RESULTS There were no differences between groups at inclusion ( baseline ) regarding any variables . During the three months treatment period , five subjects ( 8 % ) dropped out , and another seven ( 11 % ) dropped out at one-year follow-up . At the end of treatment , both pain and function had improved significantly in favour of the HD therapy , between-group differences in VAS were -2.7 ( -3.9 to 0.9 ) , and for activity limitations , the between-group differences in the SRQ increased by 24.5 points ( 14.5 - 35.7 ) . The differences between groups were both statistically and clinical ly significant at 6 and 12 months follow-up . CONCLUSION In subjects with long-term subacromial pain syndrome , HD medical exercise therapy is superior to a conventional LD exercise programme . For clinicians to obtain similar positive results with HD medical exercise therapy , factors such as good communication skills , constant close personal supervision during exercise treatment and having from three to five subjects in a group setting are important Background : Dysfunction in the kinetic chain caused by poor scapula stabilization can contribute to shoulder injuries and Shoulder Impingement Syndrome ( SIS ) . The purpose of this study was to compare the effectiveness of two treatment approaches scapular stabilization based exercise therapy and physical therapy in patients with SIS . Methods : The study is a r and omized clinical trial in which 68 patients with SIS were r and omly assigned in two groups of exercise therapy ( ET ) and physical therapy ( PT ) and received 18 sessions of treatment . Pain , shoulders ' range of abduction and external rotation , shoulder protraction , scapular rotation and symmetry as well as postural assessment and Pectoralis minor length were evaluated pre and post intervention . The paired- sample t test and the independent sample t test were applied respectively to determine the differences in each group and between two groups . Results : Our findings indicated significant differences in abduction and external rotation range , improvement of forward shoulder translation and increase in the flexibility of the involved shoulder between the two groups ( respectively ; p=0.024 , p=0.001 , p<0/0001 , p<0/0001 ) . No significant difference was detected in pain reduction between the groups ( p=0.576 ) . Protraction of the shoulder ( p<0.0001 ) , forward head posture ( p<0/0001 ) and mid thoracic curvature ( p<0.0001 ) revealed a significant improvement in the ET group . Apparent changes occurred in scapular rotation and symmetry in both groups but no significant differences were observed between the two groups ( respectively ; p=0.183 , p=0.578 ) . Conclusion : The scapular stabilization based exercise intervention was successful in increasing shoulder range , decreasing forward head and shoulder postures and Pectoralis minor flexibility Abstract Scapula taping is a commonly used adjunctive treatment for shoulder im- pingement pathology . However , this intervention has not previously been subject to formal investigation . A pilot single-blind r and omized controlled trial was conducted to evaluate facilitatory taping as an adjunct to routine physiotherapy management . Twenty-two sub- jects with unilateral shoulder impingement symptoms were r and omized into a taping with routine physiotherapy or a routine physiotherapy only group . The intervention group had scapula taping applied three times per week for the first two weeks of their treatment . All subjects were assessed at baseline , then at 2 and 6 weeks after the commencement of treat- ment . Pain and functional ability were assessed using the Shoulder Pain and Disability In- dex , range of shoulder elevation , and self-reported pain on elevation . At 2 weeks , the taping group demonstrated a strong trend toward reduced pain both on self-reported activity ( SPADI pain subscale mean for taping 27.0 versus 41.5 for control ) and pain during mea- sured abduction ( mean VAS 22.8 for taped , 46.8 for control ) , statistical power being limited by small sample size . No similar trend was evident in the SPADI disability subscale . The magnitude of the differences was reduced at 6-week follow-up . This study provides prelimi- nary evidence for a short-term role for scapula taping as an adjunct to routine physiother- apy in the management of shoulder impingement symptoms but also highlights the need for consideration on a case basis relating to risk factors for skin reaction Background Painful shoulders pose a substantial socioeconomic burden . A prospect i ve cost-of-illness study was performed to assess the costs associated with healthcare use and loss of productivity in patients with shoulder pain in primary health care in Sweden . Methods The study was performed in western Sweden , in a region with 24 000 inhabitants . Data were collected during six months from electronic patient records at three primary healthcare centres in two municipalities . All patients between 20 and 64 years of age who presented with shoulder pain to a general practitioner or a physiotherapist were included . Diagnostic codes were used for selection , and the cases were manually controlled . The cost for sick leave was calculated according to the human capital approach . Sensitivity analysis was used to explore uncertainty in various factors used in the model . Results 204 ( 103 women ) patients , mean age 48 ( SD 11 ) years , were registered . Half of the cases were closed within six weeks , whereas 32 patients ( 16 % ) remained in the system for more than six months . A fifth of the patients were responsible for 91 % of the total costs , and for 44 % of the healthcare costs . The mean healthcare cost per patient was € 326 ( SD 389 ) during six months . Physiotherapy treatments accounted for 60 % . The costs for sick leave contributed to 84 % of the total costs . The mean annual total cost was € 4139 per patient . Estimated costs for secondary care increased the total costs by one third . Conclusions The model applied in this study provides valuable information that can be used in cost evaluations . Costs for secondary care and particularly for sick leave have a major influence on total costs and interventions that can reduce long periods of sick leave are warranted PURPOSE This study aim ed to investigate the effect of elastic taping on kinematics , muscle activity and strength of the scapular region in baseball players with shoulder impingement . SCOPE Seventeen baseball players with shoulder impingement were recruited from three amateur baseball teams . All subjects received both the elastic taping ( Kinesio Tex ) and the placebo taping ( 3 M Micropore tape ) over the lower trapezius muscle . We measured the 3-dimensional scapular motion , electromyographic ( EMG ) activities of the upper and lower trapezius , and the serratus anterior muscles during arm elevation . Strength of the lower trapezius was tested prior to and after each taping application . The results of the analyses of variance ( ANOVA ) with repeated measures showed that the elastic taping significantly increased the scapular posterior tilt at 30 degrees and 60 degrees during arm raising and increased the lower trapezius muscle activity in the 60 - 30 degrees arm lowering phase ( p<0.05 ) in comparison to the placebo taping . CONCLUSIONS The elastic taping result ed in positive changes in scapular motion and muscle performance . The results supported its use as a treatment aid in managing shoulder impingement problems The purpose of this clinical trial is to compare the effectiveness of a scapular-focused treatment with a control therapy in patients with shoulder impingement syndrome . Therefore , a r and omized clinical trial with a blinded assessor was used in 22 patients with shoulder impingement syndrome . The primary outcome measures included self-reported shoulder disability and pain . Next , patients were evaluated regarding scapular positioning and shoulder muscle strength . The scapular-focused treatment included stretching and scapular motor control training . The control therapy included stretching , muscle friction , and eccentric rotator cuff training . Main outcome measures were the shoulder disability question naire , diagnostic tests for shoulder impingement syndrome , clinical tests for scapular positioning , shoulder pain ( visual analog scale ; VAS ) , and muscle strength . A large clinical ly important treatment effect in favor of scapular motor control training was found in self-reported disability ( Cohen ’s d = 0.93 , p = 0.025 ) , and a moderate to large clinical ly important improvement in pain during the Neer test , Hawkins test , and empty can test ( Cohen ’s d 0.76 , 1.04 , and 0.92 , respectively ) . In addition , the experimental group demonstrated a moderate ( Cohen ’s d = 0.67 ) improvement in self-experienced pain at rest ( VAS ) , whereas the control group did not change . The effects were maintained at three months follow-up Shoulder tendon injuries are frequently seen in the presence of abnormal scapular motion , termed scapular dyskinesis . The cause and effect relationship between scapular dyskinesis and shoulder injury has not been directly defined . We developed and used an animal model to examine the initiation and progression of pathological changes in the rotator cuff and biceps tendon . Sixty male Sprague-Dawley rats were r and omized into two groups : nerve transection ( to induce scapular dyskinesis , SD ) or sham nerve transection ( control ) . The animals were euthanized 4 and 8 weeks after surgery . Shoulder function and passive joint mechanics were evaluated over time . Tendon mechanical , histological , organizational , and compositional properties were evaluated at both time points . Gross observation demonstrated alterations in scapular motion , consistent with scapular " winging . " Shoulder function , passive internal range of motion , and tendon mechanical properties were significantly altered . Histology results , consistent with tendon pathology ( rounded cell shape and increased cell density ) , were observed , and protein expression of collagen III and decorin was altered . This study presents a new model of scapular dyskinesis that can rigorously evaluate cause and effect relationships in a controlled manner . Our results identify scapular dyskinesis as a causative mechanical mechanism for shoulder tendon pathology A systematic review of the literature was performed to evaluate the role of exercise in treating rotator cuff impingement and to synthesize a st and ard evidence -based rehabilitation protocol . Eleven r and omized , controlled trials ( level 1 and 2 ) evaluating the effect of exercise in the treatment of impingement were identified . Data regarding demographics , methodology , and outcomes of pain , range of motion , strength , and function were recorded . Individual components of each rehabilitation program were catalogued . Effectiveness was determined by statistical and clinical significance . Although many articles had method ologic concerns , the data demonstrate that exercise has statistically and clinical ly significant effects on pain reduction and improving function , but not on range of motion or strength . Manual therapy augments the effects of exercise , yet supervised exercise was not different than home exercise programs . Information regarding specific components of the exercise programs was synthesized into a gold st and ard rehabilitation protocol for future studies on the nonoperative treatment of rotator cuff impingement OBJECTIVE The study investigated the effectiveness of stretching , strengthening exercises , and the scapular stabilization exercises on the pain , shoulder range of motion ( ROM ) , muscle strength , joint position sense ( JPS ) , scapular dyskinesis and quality of life ( OL ) in the patients with subacromial impingement syndrome ( SIS ) . METHODS 27 women and 13 men , mean age 51 ( 24 - 71 ) years old , were included in this study . All the patients were separated into 2 groups according to simple r and om table . Stretching and strengthening exercises were given to the group I ( n=20 ) and scapular stabilization exercises were added to the group II ( n=20 ) . The pain severity , shoulder ROM , muscle strength , JPS , lateral scapular slide test ( LSST ) , Western Ontario Rotator Cuff ( WORC ) Index were evaluated before and after treatment . Patients completed a 6-week rehabilitation program , three times a week . RESULTS The results showed that all measurements improved statistically in both groups after treatment ( p < 0.05 ) . And the improvements in the muscle strength , JPS and scapular dyskinesia were significantly different in group II ( p < 0.05 ) . CONCLUSION It is suggested that in the treatment of SIS ; scapular stabilization exercises , given with stretching and strengthening exercises , can be more effective in increasing the muscle strength , developing the JPS and decreasing the scapular dyskinesis BACKGROUND Multiple factors have been associated with the presence of a subacromial pain syndrome ( SPS ) , including deficits in performance of scapular and glenohumeral muscles . Such deficits can lead to inadequate kinematics and decreased acromiohumeral distance ( AHD ) . Exercises that aim at correcting these deficits , such as movement training , were suggested to improve symptoms and functional limitations . To date , few studies have assessed outcomes following an intervention focused on movement training . OBJECTIVES Evaluate the effects of a rehabilitation program based on movement training on symptoms , functional limitations and AHD in individuals with SPS . DESIGN Prospect i ve single group pre-post design . METHODS Twenty-five participants with SPS ( SPS group ) participated in a 6-week program . Twenty asymptomatic volunteers were recruited for normative AHD values ( control group ) . Outcomes of both groups were evaluated at baseline and 6 weeks , i.e. immediately following intervention for the SPS group . Changes in symptoms and functional limitations for SPS group were assessed using the Western Ontario Rotator Cuff ( WORC ) index and Disability of the Arm Shoulder and H and ( DASH ) question naire . Changes in AHD for both groups were assessed using ultrasonographic measures . RESULTS Following the rehabilitation program , the scores on WORC and DASH were significantly improved ( p < 0.001 ) . AHD increased significantly in the SPS group ( p = 0.019 ) , especially in a subgroup with initial deficits ( p < 0.001 ) . CONCLUSION The rehabilitation program yielded improvements in symptoms and functional limitations in participants with SPS . Moreover , it led to an increase of the AHD -- thus potentially decreasing subacromial compression , particularly in participants with an initially smaller AHD . The trial was registered at Clinical Trials.gov : identifier -- NCT02395770 OBJECTIVE To assess pain , function , quality of life , and muscle strength in patients with shoulder impingement syndrome who participated in muscle strengthening exercises . METHODS A total of 60 patients diagnosed with shoulder impingement syndrome were selected from the clinics of the Federal University of São Paulo and r and omly distributed into experimental and control groups . Patients were evaluated regarding pain , function , quality of life , muscle strength , and the number of antiinflammatory drugs and analgesics taken . Patients then participated in the progressive resistance training program for the musculature of the shoulder , which was held twice a week for 2 months , while the control group remained on a waiting list . RESULTS Sixty patients were r and omly allocated to the experimental group ( 21 women and 9 men , mean age 56.3 years ) and control group ( 25 women and 5 men , mean age 54.8 years ) . Patients from the experimental group showed an improvement from 4.2 cm to 2.4 cm on a 10-cm visual analog scale ( P < 0.001 ) regarding pain at rest and from 7.4 cm to 5.2 cm ( P < 0.001 ) regarding pain during movement . Function went from 44.0 to 33.2 ( P < 0.007 ) using the Disabilities of the Arm , Shoulder , and H and assessment and domains from the Short Form 36 . There was a statistically significant difference in improvement in pain and function between patients in the experimental group and those in the control group ( P < 0.05 ) . CONCLUSION The progressive resistance training program for the musculature of the shoulder in patients with shoulder impingement syndrome was effective in reducing pain and improving function and quality of life OBJECTIVE The aim of this study was to evaluate the initial effects of scapular mobilization ( SM ) on shoulder range of motion ( ROM ) , scapular upward rotation , pain , and function . DESIGN Pretest-posttest for 3 groups ( SM , sham , and control ) . SETTING A double-blinded , r and omized , placebo-controlled trial was conducted to evaluate the initial effect of the SM at a sports physiotherapy clinic . PARTICIPANTS 39 subjects ( 22 women , 17 men ; mean age 54.30 + /- 14.16 y , age range 20 - 77 y ) . INTERVENTIONS A visual analog scale , ROM , scapular upward rotation , and function were assessed before and just after SM . SM ( n = 13 ) consisted of the application of superoinferior gliding , rotations , and distraction to the scapula . The sham ( n = 13 ) condition replicated the treatment condition except for the h and positioning . The control group ( n = 13 ) did not undergo any physiotherapy and rehabilitation program . MAIN OUTCOME MEASURES Pain severity was assessed with a visual analog scale . Scapular upward rotation was measured with a baseline digital inclinometer . Constant Shoulder Score ( CSS ) was used to measure shoulder function . RESULTS After SM , we found significant improvements for shoulder ROM , scapular upward rotation , and CSS between pretreatment and posttreatment compared with the sham and control groups . In the sham group , shoulder-ROM values increased or decreased for the shoulder and scapular upward rotation was not changed . Pain , ROM , and physical function of the shoulder were not significantly different in the sham group than in controls ( P > .05 ) . CONCLUSIONS SM may be a useful manual therapy technique to apply to participants with a painful limitation of the shoulder . SM increases ROM and decreases pain intensity Background Altered muscle activity in the scapular muscles is commonly believed to be a factor contributing to shoulder impingement syndrome . However , one important measure of the muscular coordination in the scapular muscles , the timing of the temporal recruitment pattern , is undetermined . Purpose To evaluate the timing of trapezius muscle activity in response to an unexpected arm movement in athletes with impingement and in normal control subjects . Study Design Prospect i ve cohort study . Methods Muscle latency times were measured in all three parts of the trapezius muscle and in the middle deltoid muscle of 39 “ overh and athletes ” with shoulder impingement and compared with that of 30 overh and athletes with no impingement during a sudden downward falling movement of the arm . Results There were significant differences in the relative muscle latency times between the impingement and the control group subjects . Those with impingement showed a delay in muscle activation of the middle and lower trapezius muscle . Conclusion The results of this study indicate that overh and athletes with impingement symptoms show abnormal muscle recruitment timing in the trapezius muscle . The findings support the theory that impingement of the shoulder may be related to delayed onset of contraction in the middle and lower parts of the trapezius muscle OBJECTIVE To determine the effects of scapular mobilization on function , pain , range of motion , and satisfaction in patients with subacromial impingement syndrome ( SAIS ) . DESIGN R and omized , double-blind , placebo-controlled clinical trial . SETTING University hospital clinics in Turkey . PARTICIPANTS 66 participants ( mean ± SD age 52.06 ± 3.71 y ) with SAIS . INTERVENTIONS Participants were r and omized into 3 groups : scapular mobilization , sham scapular mobilization , and supervised exercise . Before the interventions transcutaneous electrical stimulation and hot pack were applied to all groups . Total intervention duration for all groups was 3 wk with a total of 9 treatment sessions . MAIN OUTCOME MEASURES Shoulder function and pain intensity were primary outcome measures ; range of motion and participant satisfaction were secondary outcome measures . Shoulder function was assessed with the short form of the Disabilities of the Arm , Shoulder and H and Question naire ( DASH ) . A visual analog scale was used to evaluate pain severity . Active range of motion was measured with a universal goniometer . A 7-point Likert scale was used to evaluate satisfaction . Outcome measurements were performed at baseline , before visits 5 and 10 , 4 wk after visit 9 , and 8 wk after visit 9 . RESULTS There was no group difference for DASH score ( P = .75 ) , pain at rest ( P = .41 ) , pain with activity ( P = .45 ) , pain at night ( P = .74 ) , and shoulder flexion ( P = .65 ) , external rotation ( P = .63 ) , and internal rotation ( P = .19 ) . There was a significant increase in shoulder motion and function and a significant decrease in pain across time when all groups were combined ( P < .001 ) . The level of satisfaction was not significantly different for any of the questions about participant satisfaction between all groups ( P > .05 ) . CONCLUSION There was not a significant advantage of scapular mobilization for shoulder function , pain , range of motion , and satisfaction compared with sham or supervised-exercise groups in patients with SAIS A shoulder pain and disability index ( SPADI ) was developed to measure the pain and disability associated with shoulder pathology . The SPADI is a self-administered index consisting of 13 items divided into two subscales : pain and disability . Thirty-seven male patients with shoulder pain were used in a study to examine the measurement characteristics of the SPADI . Test-retest reliability of the SPADI total and subscale scores ranged from 0.6377 to 0.6552 . Internal consistency ranged from 0.8604 to 0.9507 . SPADI total and subscale scores were highly negatively correlated with shoulder range of motion ( ROM ) supporting the criterion validity of the index . Principal components factor analysis with and without varimax rotation supported the construct validity of the total SPADI and its subscales . High negative correlations between changes in SPADI scores and changes in shoulder ROM indicated the SPADI detected changes in clinical status over short time intervals . The SPADI should prove useful for both clinical and research purpose OBJECTIVE Evidence for effective management of shoulder impingement is limited . The present study aim ed to quantify the clinical , neurophysiological , and biomechanical effects of a scapular motor control retraining for young individuals with shoulder impingement signs . METHOD Sixteen adults with shoulder impingement signs ( mean age 22 ± 1.6 years ) underwent the intervention and 16 healthy participants ( 24.8 ± 3.1years ) provided reference data . Shoulder function and pain were assessed using the Shoulder Pain and Disability Index ( SPADI ) and other question naires . Electromyography ( EMG ) and 3-dimensional motion analysis was used to record muscle activation and kinematic data during arm elevation to 90 ° and lowering in 3 planes . Patients were assessed pre and post a 10-week motor control based intervention , utilizing scapular orientation retraining . RESULTS Pre-intervention , patients reported pain and reduced function compared to the healthy participants ( SPADI in patients 20 ± 9.2 ; healthy 0 ± 0 ) . Post-intervention , the SPADI scores reduced significantly ( P < .001 ) by a mean of 10 points ( ±4 ) . EMG showed delayed onset and early termination of serratus anterior and lower trapezius muscle activity pre-intervention , which improved significantly post-intervention ( P < .05 ) . Pre-intervention , patients exhibited on average 4.6 - 7.4 ° less posterior tilt , which was significantly lower in 2 arm elevation planes ( P < .05 ) than healthy participants . Post-intervention , upward rotation and posterior tilt increased significantly ( P < .05 ) during 2 arm movements , approaching the healthy values . CONCLUSION A 10-week motor control intervention for shoulder impingement increased function and reduced pain . Recovery mechanisms were indicated by changes in muscle recruitment and scapular kinematics . The efficacy of the intervention requires further examined in a r and omized control trial BACKGROUND Rotator cuff tears are common conditions that often require surgical repair to improve function and to relieve pain . Unfortunately , repair failure remains a common problem after rotator cuff repair surgery . Several factors may contribute to repair failure , including age , tear size , and time from injury . However , the mechanical mechanisms result ing in repair failure are not well understood , making clinical management difficult . Specifically , altered scapular motion ( termed scapular dyskinesis ) may be one important and modifiable factor contributing to the risk of repair failure . Therefore , the objective of this study was to determine the effect of scapular dyskinesis on supraspinatus tendon healing after repair . METHODS A rat model of scapular dyskinesis was used . Seventy adult male Sprague-Dawley rats ( 400 - 450 g ) were r and omized into 2 groups : nerve transection of the accessory and long thoracic nerves ( SD ) or sham nerve transection ( Sham control ) . After this procedure , all rats underwent unilateral detachment and repair of the supraspinatus tendon . All rats were sacrificed at 2 , 4 , and 8 weeks after surgery . Shoulder function , passive joint mechanics , and tendon properties ( mechanical , histologic , organizational , and compositional ) were evaluated . RESULTS Scapular dyskinesis alters joint function and may lead to compromised supraspinatus tendon properties . Specifically , diminished mechanical properties , altered histology , and decreased tendon organization were observed for some parameters . CONCLUSION This study identifies scapular dyskinesis as one underlying mechanism leading to compromise of supraspinatus healing after repair . Identifying modifiable factors that lead to compromised tendon healing will help improve clinical outcomes after repair Background Many bibliographic data bases index research studies evaluating the effects of health care interventions . One study has concluded that the Physiotherapy Evidence Data base ( PEDro ) has the most complete indexing of reports of r and omized controlled trials of physical therapy interventions , but the design of that study may have exaggerated estimates of the completeness of indexing by PEDro . Objective The purpose of this study was to compare the completeness of indexing of reports of r and omized controlled trials of physical therapy interventions by 8 bibliographic data bases . Design This study was an audit of bibliographic data bases . Methods Prespecified criteria were used to identify 400 reports of r and omized controlled trials from the reference lists of systematic review s published in 2008 that evaluated physical therapy interventions . Eight data bases ( AMED , CENTRAL , CINAHL , EMBASE , Hooked on Evidence , PEDro , PsycINFO , and PubMed ) were search ed for each trial report . The proportion of the 400 trial reports indexed by each data base was calculated . Results The proportions of the 400 trial reports indexed by the data bases were as follows : CENTRAL , 95 % ; PEDro , 92 % ; PubMed , 89 % ; EMBASE , 88 % ; CINAHL , 53 % ; AMED , 50 % ; Hooked on Evidence , 45 % ; and PsycINFO , 6 % . Almost all of the trial reports ( 99 % ) were found in at least 1 data base , and 88 % were indexed by 4 or more data bases . Four trial reports were uniquely indexed by a single data base only ( 2 in CENTRAL and 1 each in PEDro and PubMed ) . Limitations The results are only applicable to search ing for English- language published reports of r and omized controlled trials evaluating physical therapy interventions . Conclusions The 4 most comprehensive data bases of trial reports evaluating physical therapy interventions were CENTRAL , PEDro , PubMed , and EMBASE . Clinicians seeking quick answers to clinical questions could search any of these data bases knowing that all are reasonably comprehensive . PEDro , unlike the other 3 most complete data bases , is specific to physical therapy , so studies not relevant to physical therapy are less likely to be retrieved . Research ers could use CENTRAL , PEDro , PubMed , and EMBASE in combination to conduct exhaustive search es for r and omized trials in physical therapy |
12,150 | 24,998,542 | Education intervention reduced the pain of cancer patients .
Therefore , patient education could be considered to be an effective method of cancer pain management . | BACKGROUND Many cancer patients experience poor pain control due to various factors , including misconceptions regarding the use of opioid analgesics .
For management of cancer pain , interventions involving education of both patients and physicians have been attempted .
OBJECTIVES This review aim ed to assess the current evidence of the benefits of education for the management of cancer pain . | 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 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 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 PURPOSE / OBJECTIVES To assess the effect of an educational homecare program on pain relief in patients with advanced cancer . DESIGN Quasi-experimental ( pretest post-test , nonequivalent group ) . SETTING Four community-based primary care centers providing social and healthcare services in the Quebec City region of Canada . SAMPLE 80 homecare patients with advanced cancer who were free of cognitive impairment , who presented with pain or were taking analgesics to relieve pain , and who had a life expectancy of six weeks or longer . METHODS The educational intervention included information regarding pain assessment and monitoring using a daily pain diary and the provision of specific recommendations in case of loss of pain control . Pain intensity data were collected prior to the intervention , and re assessment s were made two and four weeks later . Data on beliefs were collected at baseline and two weeks . All data were collected by personal interviews . MAIN RESEARCH VARIABLES Patients beliefs about the use of opioids ; average and maximum pain intensities . FINDINGS Patients beliefs regarding the use of opioids were modified successfully following the educational intervention . Average pain was unaffected in the control group and was reduced significantly in patients who received the educational program . The reduction remained after controlling for patients initial beliefs . Maximum pain decreased significantly over time in both the experimental and control groups . CONCLUSIONS An educational intervention can be effective in improving the monitoring and relief of pain in patients with cancer living at home . IMPLICATION S FOR NURSING Homecare nurses can be trained to effectively administer the educational program during their regular homecare visits 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 AIM OF THE STUDY To investigate the role of district nurses in the care of cancer patients with chronic pain at home , as well as the effects of a Pain Education Programme for patients and their district nurses . The Pain Education Programme consisted of a tailored multi- method approach in which they were educated about pain , instructed how to report pain , and how to contact health care providers . BACKGROUND No educational programs for patients in pain have been studied in out patients nor integrated with the home care provided . DESIGN AND METHODS One hundred and four patients and their 115 district nurses were enrolled in a prospect i ve , longitudinal , r and omized controlled study . The primary outcome of interest was type of care provided by district nurses , satisfaction with the pain treatment , and agreement in estimating patients ' pain intensity . RESULTS Results showed that continuity of care was poor as only 36 % of the district nurses were informed about patients ' pain by hospital nurses . Pain was rarely the reason for referring the patient to district nursing after discharge . Although pain control was not a main reason for district nurses to visit a patient , pain was a subject for discussion in 76 % of visits . Besides discussing the pain problem with patients , district nurses provided only a few pain-relieving interventions . District nurses r and omized to the intervention group significantly better estimated patients ' pain intensity , and were more satisfied about patients ' pain treatment , but no differences were found in their assessment of patients ' pain relief . CONCLUSIONS These findings suggest a significant but moderate effect of the Pain Education Programme , with district nurses only playing a minor role in the treatment of cancer pain CONTEXT In Korea , many health care professionals have shown increased concern about the management of cancer pain . Five years after a pain management guideline was distributed to Korean physicians , the Korean Society of Hospice and Palliative Care evaluated the change in cancer pain management . The period evaluated was between 2001 and 2006 . METHODS We did a prospect i ve , cross-sectional cancer pain survey on the change of the pain prevalence and pain intensity , its impact on daily activities and the adequacy of pain management between 2001 and 2006 . RESULTS Overall , 7565 patients were enrolled from 72 cancer hospitals in the 2001 cancer pain survey and 7245 patients were enrolled from 63 cancer hospitals in the 2006 cancer pain survey . The overall prevalence of cancer pain and the percentage of patients reporting a negative pain management index were significantly decreased in the 2006 cancer pain survey compared with the 2001 cancer pain survey ( 44.9 % vs. 52.1 % , P<0.0001 and 41.6 % vs. 45.0 % , respectively , P=0.0005 ) . However , in 2006 , physicians did not prescribe analgesics to 25.8 % of the patients with severe pain and they did not adjust the prescribed analgesics properly in 47.4 % of the patients with severe pain . CONCLUSION Some improvement in cancer pain management was noted during the five years between 2001 and 2006 . However , all of the physicians who care for cancer patients should pay more attention to cancer pain management , and an educational program for cancer pain management should be distributed to all of the physicians who care for cancer patients OBJECTIVES To develop and vali date a new risk-of-bias tool for nonr and omized studies ( NRSs ) . STUDY DESIGN AND SETTING We developed the Risk of Bias Assessment Tool for Nonr and omized Studies ( RoBANS ) . A validation process with 39 NRSs examined the reliability ( interrater agreement ) , validity ( the degree of correlation between the overall assessment s of RoBANS and Method ological Index for Nonr and omized Studies [ MINORS ] , obtained by plotting the overall risk of bias relative to effect size and funding source ) , face validity with eight experts , and completion time for the RoBANS approach . RESULTS RoBANS contains six domains : the selection of participants , confounding variables , the measurement of exposure , the blinding of the outcome assessment s , incomplete outcome data , and selective outcome reporting . The interrater agreement of the RoBANS tool except the measurement of exposure and selective outcome reporting domains ranged from fair to substantial . There was a moderate correlation between the overall risks of bias determined using RoBANS and MINORS . The observed differences in effect sizes and funding sources among the assessed studies were not correlated with the overall risk of bias in these studies . The mean time required to complete RoBANS was approximately 10 min . The external experts who were interviewed evaluated RoBANS as a " fair " assessment tool . CONCLUSIONS RoBANS shows moderate reliability , promising feasibility , and validity . The further refinement of this tool and larger validation studies are required & 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 The purpose of this pilot study was to explore the effectiveness of a pain education program to overcome patient-related barriers in managing cancer pain for Taiwanese home care patients with cancer . The pain education program was developed based on previous studies of Taiwanese patient-related barriers to cancer pain management . The Barriers Question naire – Taiwan form , the Brief Pain Inventory , the Medication Adherence Question naire , and a demographic question naire were used for data collection . The sample consisted of 18 patients in the experimental group and 19 patients in the control group . Descriptive statistics , t tests , and paired t tests were used to analyze the data . Results of this study revealed that patients who received the pain educational program had significantly greater reduction in Barriers Question naire – Taiwan form scores and more improvement in medication adherence compared with patients who did not participate in the program . When compared to pretest scores , patients scores after receiving the pain education intervention showed significant improvement on the Barriers Question naire – Taiwan form , medication adherence , pain intensity , and pain interference . The results of this study support the effectiveness of the pain education program on overcoming the barriers to cancer pain management for Taiwanese home care patients with cancer 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 This preliminary study tested the efficacy of a partner-guided cancer pain management protocol for patients who are at the end of life . Seventy-eight advanced cancer patients meeting criteria for hospice eligibility and their partners were r and omly assigned to a partner-guided pain management training intervention , or usual care control condition . The partner-guided pain management training protocol was a three-session intervention conducted in patients ' homes that integrated educational information about cancer pain with systematic training of patients and partners in cognitive and behavioral pain coping skills . Data analyses revealed that the partner-guided pain management protocol produced significant increases in partners ' ratings of their self-efficacy for helping the patient control pain and self-efficacy for controlling other symptoms . Partners receiving this training also showed a trend to report improvements in their levels of caregiver strain . Overall , the results of this preliminary study suggest that a partner-guided pain management protocol may have benefits in the context of cancer pain at the end of life . Given the significance of pain at the end of life , future research in this area appears warranted Concerns about reporting pain and using analgesics ultimately can contribute to poor pain management for many individuals . A nursing intervention to address these " patient-related barriers " was developed based on Johnson 's self-regulation theory . The purpose of this pilot study was to determine whether provision of individually tailored sensory and coping information about analgesic side effects and specific information to counter misconceptions would enhance pain management in a sample of 43 women with gynecologic cancers . It was hypothesized that at 1-month post-test and 2-month follow-up , those subjects r and omized to the information condition would ( a ) have lower barriers scores ; ( b ) use more adequate analgesic medication ; ( c ) have lower analgesic side effect scores ; ( d ) have lower pain intensity scores ; and ( e ) experience less pain interference with life and better overall quality of life compared to those in the care-as-usual control group . There was no main effect for group on any of the dependent variables . Rather , all women reported a decrease in barriers between baseline and 2-month follow-up ( p<.05 ) ; all subjects experienced a decrease in pain interference with life scores between baseline and 1-month post-test ( p<.05 ) ; and there was a significant shift of women from unacceptable pain management at baseline to acceptable pain management at 1-month post-test ( p<.05 ) . In addition , the majority of women reported that the intervention contained novel and useful information that helped them to feel more comfortable taking pain medication , to be less concerned about addiction , and helped them talk more openly about pain with a doctor or nurse |
12,151 | 16,207,320 | Use of any oral opioid produced higher rates of adverse events than did placebo .
Because most trials were short , less than four weeks , and because few titrated the dose , these results have limited applicability to longer-term use of opioids in clinical practice . | Adverse events of opioids may restrict their use in non-cancer pain .
Analysis of the incidence of common adverse events in trials conducted in non-cancer pain has usually been limited to opioids used to treat severe pain according to the WHO three-step ladder . | 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 CONTEXT R and omized trials with adequate sample size offer an opportunity to assess the safety of new medications in a controlled setting ; however , generalizable data on drug safety reporting are sparse . OBJECTIVE To scrutinize the completeness of safety reporting in r and omized trials . DESIGN , SETTING , AND PATIENTS Survey of safety reporting in 192 r and omized drug trials 7 diverse topics with sample sizes of at least 100 patients and at least 50 patients in a study arm ( N = 130074 patients ) . Trial reports were identified from comprehensive meta-analyses in 7 medical areas . MAIN OUTCOME MEASURES Adequate reporting of specific adverse effects and frequency and reasons for withdrawals due to toxic effects ; article space allocated to safety reporting and predictors of such reporting . RESULTS Severity of clinical adverse effects and laboratory-determined toxicity was adequately defined in only 39 % and 29 % of trial reports , respectively . Only 46 % of trials stated the frequency of specific reasons for discontinuation of study treatment due to toxicity . For these 3 parameters , there was significant heterogeneity in rates of adequate reporting across topics ( P = .003 , P<.001 , and P = .02 , respectively ) . Overall , the median space allocated to safety results was 0.3 page . A similar amount of space was devoted to contributor names and affiliations ( P = .16 ) . On average , the percentage of space devoted to safety in the results section was 9.3 % larger in trials involving dose comparisons than in those that did not ( P<.001 ) and 3.8 % smaller in trials reporting statistically significant results for efficacy outcomes ( P = .047 ) . CONCLUSIONS The quality and quantity of safety reporting vary across medical areas , study design s , and setting s but they are largely inadequate . Current st and ards for safety reporting in r and omized trials should be revised to address this inadequacy We assessed the quality of assessment and reporting of adverse effects in r and omized , double-blind clinical trials of single-dose acetaminophen or ibuprofen compared with placebo in moderate to severe postoperative pain . Reports were identified by systematic search ing of a number of bibliographic data bases ( e.g. , MEDLINE ) . Information on adverse effect assessment , severity and reporting , patient withdrawals , and anesthetic used was extracted . Compliance with former guidelines for adverse effect reporting was noted . Fifty-two studies were included ; two made no mention of adverse effects . No method of assessment was given in 19 studies . Twenty trials failed to report the type of anesthetic used , eight made no mention of patient withdrawals , and nine did not state the severity of reported adverse effects . Only two studies described the method of assessment of adverse effect severity . When all adverse effect data were pooled , significantly more adverse effects were reported with active treatment than with placebo . For individual adverse effects , there was no difference between active ( acetaminophen 1000 mg or ibuprofen 400 mg ) and placebo ; the exception was significantly more somnolence/drowsiness with ibuprofen 400 mg . Ninety percent of trials reporting somnolence/drowsiness with ibuprofen 400 mg were in dental pain . All studies published after 1994 complied with former guidelines for adverse effect reporting . Different methods of assessing adverse effects produce different reported incidence : patient diaries yielded significantly more adverse effects than other forms of assessment . We recommend guidelines for reporting adverse effect information in clinical trials There is controversy about whether the lack of response of some chronic pain to opioid treatment is absolute or relative . It is widely believed that nociceptive pain is responsive to opioids whereas neuropathic pain tends not to be . We have used a method of patient-controlled analgesia ( PCA ) with simultaneous nurse-observer measurement of analgesia , mood , and adverse effects to address these issues . Ten patients with chronic pain were given morphine at two concentrations ( 10 and 30 mg/ml ) by PCA in two separate sessions in a double-blind r and omised crossover study . Before the study a clinical judgment was made as to whether each pain was nociceptive or neuropathic . Seven patients showed good analgesic responses ( more than 70 mm pain relief on a visual-analogue scale ) of pain at rest , two patients poor responses ( less than 30 mm pain relief ) , and one a moderate response with both concentrations ( 30 - 70 mm pain relief ) . The response to morphine was consistent ( greater and faster relief with the higher concentration ) in nine patients . Two patients had pain on movement that responded moderately to low-concentration morphine and well to the higher concentration . All patients with pains judged to be nociceptive showed good analgesic responses compared with half of those with neuropathic pain . There was no evidence that analgesic responses in patients with neuropathic pain were due to changes in mood . This PCA method is a quick and efficient tool to determine the consistency of the analgesic response . Such consistency can guide the clinician as to whether continued or higher-dose opioid treatment will produce good analgesia . An inconsistent response points to the use of other pain-relieving strategies & NA ; The aim of the present study has been to assess the responsiveness of various types of chronic pain to opioids given i.v . and tested against placebo in a double‐blind , r and omized fashion . Pain classified as primary nociceptive was effectively alleviated ( P > 0.001 ) while neuropathic deafferentation pain was not significantly influenced by morphine or equivalent doses of other opioids . Also ‘ idiopathic ’ pain , defined as chronic pain with no or little demonstrable pathology , failed to respond . The results were not related to whether the patients were regular users of narcotic analgesics or not . The outcome of our double‐blind opioid test has proved useful to justify a continued , or discontinued , use of narcotic medication in individual patients . It may also support the indication and choice of invasive stimulation procedures ( spinal cord or brain ) . The results of the study illustrate the misconception of chronic pain as an entity and highlight the importance of recognizing different neurobiological mechanisms and differences in responsiveness to analgesic drugs as well as to non‐pharmacological modes of treatment . The opioid test has thus become a valuable tool in pain analysis and helpful as a guide for further treatment & 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 Healthy university students and hospital staff taking no medications were surveyed by question naire to obtain data on the occurrence of many symptoms often listed as side effects of drugs |
12,152 | 21,915,699 | Conclusions Preservation of the spleen and pancreas during extended lymphadenectomy for gastric cancer decreases complications with no clear evidence of improvement or detriment to overall survival | Background The overall prognosis and survival of patients with advanced gastric cancer are generally poor .
Extended lymphadenectomy is recommended for patients with advanced gastric cancer ; however , splenectomy and distal pancreatectomy performed with an extended lymph node dissection may be associated with increased morbidity and mortality . | The role of the spleen in tumor immunology is still controversial in that it can either enhance or suppress the antitumor immune response depending on the tumor-bearing host . To clarify this biphasic effect of the spleen , a clinical evaluation of splenectomy in conjunction with immunotherapy and the host immune status was performed in gastric cancer patients . The effect of splenectomy and immunotherapy in 253 gastric cancer patients enrolled in a prospect i ve r and omized trial ( SIP ) was analyzed using the Cox ’s proportional hazards model in terms of the covariate interaction of the preoperative immunosuppressive acidic protein ( IAP ) level . In patients with high IAP levels ( > 580 μg/ml ) with predicted negative antitumor immune reactions splenectomy improved the prognosis . In patients with lower IAP values , conversely , the preservation of the spleen and immunotherapy demonstrated a significant benefit to survival . The spleen was shown to have a biphasic activity in terms of its antitumor immune response depending on the IAP level of the patient . The effect of immunotherapy is significantly influenced by the activity of spleen cells . The preoperative IAP level is therefore considered to be a possible indicator for the effectiveness of splenectomy and immunotherapy in curatively resected gastric cancer patients The following treatments show promise but are as yet to be established as st and ard . They should be prospect ively evaluated in appropriate clinical research setting s. Patient consent for investigational treatments should be sought and the rationale behind them given ( Refer to the Sect . 6 ‘ ‘ Commentary on investigational treatments ’ ’ for details ) . The following constitute investigational treatments : – Endoscopic submucosal dissection under exp and ed criteria – Laparoscopic gastrectomy – Local tumor resection – Neoadjuvant chemotherapy – Adjuvant chemotherapy using agents other than S-1 – Neoadjuvant chemoradiotherapy – Adjuvant chemoradiotherapy – Debulking surgery To compare the outcomes after D1 gastrectomy with those after modified D2 gastrectomy ( preserving pancreas and spleen ) performed by specialist surgeons for gastric cancer in a large UK NHS Trust . In all , 118 consecutive patients with gastric adenocarcinoma were referred by postcode , to undergo either a D1 gastrectomy ( North Gwent ( RJ ) , n=36 , median age 76 years , 21 m ) or a modified D2 gastrectomy ( South Gwent ( WL ) , n=82 , 70 years , 57 m ) . Operative mortality in the two groups of patients was similar ( D1 8.3 % vs D2 7.3 % , χ2 0.286 , DF 1 , P=0.593 ) . Overall cumulative survival at 5 years was 32 % after D1 gastrectomy compared to 59 % after D2 gastrectomy ( χ2 4.25 , DF 1 , P=0.0392 ) . In patients with stage III cancers , survival was 8 % after D1 , compared with 33 % after D2 gastrectomy ( χ2 6.43 , DF 1 , P=0.0112 ) . In a multivariate analysis , T stage ( hazard ratio 2.339 , 95 % CI 1.683–2.995 , P=0.01 ) , N stage ( hazard ratio 4.026 , 95 % CI 3.536–4.516 , P=0.0001 ) and the extent of lymphadenectomy ( hazard ratio 0.258 , 95 % CI –0.426–0.942 , P=0.0001 ) were independently associated with duration s of survival . In conclusion , modified D2 gastrectomy can improve survival four-fold for patients with stage III gastric cancer , without significantly increasing morbidity and mortality when compared with a D1 gastrectomy BACKGROUND In Japan the surgical approach to treatment of potentially curable gastric cancer , including extended lymphadenectomy , seems in retrospective surveys to give better results than the less radical procedures favoured in Western countries . There has , however , been no evidence from r and omised trials that extended lymphadenectomy ( D2 gastric resection ) confers a survival advantage . This question was addressed in a trial involving thirty-two surgeons in Europe . METHODS In a prospect i ve r and omised controlled trial , D1 resection ( level 1 lymphadenectomy ) was compared with D2 resection ( levels 1 and 2 lymphadenectomy ) . Central r and omisation ( 200 patients in each arm ) followed a staging laparotomy . FINDINGS The D2 group had greater postoperative hospital mortality ( 13 % vs 6.5 % ; p=0.04 [ 95 % Cl 9 - 18 % for D2 , 4 - 11 % for D1 ] and higher overall postoperative morbidity ( 46 % vs 28 % ; p<0.001 ) ; their postoperative stay was also longer . The excess postoperative morbidity and mortality in the D2 group was accounted for by distal pancreaticosplenectomy and splenectomy . In the whole group ( 400 patients ) , survival beyond three years was 30 % in patients whose gastrectomy included en-bloc pancreatico-splenic resection versus 50 % in the remainder . INTERPRETATION D2 gastric resections are followed by higher morbidity and mortality than D1 resections . These disadvantages are consequent upon additional pancreatectomies and distal splenectomies , and in long-term follow-up the higher mortality when the pancreas and spleen are resected may prove to nullify any survival benefit from D2 procedures BACKGROUND / AIMS This study was conducted to clarify the impact of pancreaticosplenectomy on the prognosis of patients with gastric carcinoma . METHODOLOGY Two hundred and seventy-two patients who underwent total gastrectomy with distal pancreatectomy and splenectomy were retrospectively review ed . RESULTS Lymph node metastases at the splenic hilum ( # 10 ) and along the splenic artery ( # 11 ) occurred in 12.4 % and 19.2 % of cases , respectively . The 5-year survival rate of those without metastasis at # 10 was 62.8 % . Once nodal metastasis occurred , the prognosis became very poor ; only 18.2 % in those with a single positive node and 15.4 % of those with two or more positive nodes at this location survived 5 years . Similar trends in survival were observed with respect to nodes at # 11 . When stratified by nodal status as currently determined by microscopic examination , pancreaticosplenectomy saved 4.5 % of patients with positive nodes , but was insufficient in 17.3 % of cases and was not necessary in the 78.2 % of cases who were node negative at these locations . CONCLUSIONS The data indicate that pancreaticosplenectomy can save some patients with positive nodes in these regions ; however , the small survival benefit does not provide a basis for the general application of this highly morbid procedure . To further evaluate these results in a r and omized study , selection of a subset of patients who are likely to have metastasis is the key BACKGROUND Complete surgical ( R0 ) resection remains the only potentially curative intervention for patients with localised gastric cancer . To achieve a curative resection , patients may require complex operations with resection of contiguous organs . The aim of this study was to assess how the extent of surgical resection influenced morbidity , mortality and survival in an aged non-selected population with significant comorbid disease . PATIENTS AND METHODS Data were extracted from the Scottish Audit of Gastric and Oesophageal Cancer ( SAGOC ) , a prospect i ve population -based audit of all oesophageal and gastric cancers in Scotl and between 1997 and 1999 with a minimum of 1-year follow-up . RESULTS A total of 646 patients underwent surgical exploration for gastric cancer . A significantly higher incidence of chest infections ( 18.5 vs 11 % , p < 0.05 ) and anastomotic leaks ( 14.3 vs 2.2 % , p < 0.05 ) were associated with total gastrectomy ( n=168 ) when compared to distal gastrectomy ( n=272 ) resections . A 9.2 % mortality rate and a 60 % 1-year survival were associated with gastric resection alone . Removal of the spleen ( n=131 ) , pancreas ( n=30 ) or liver resection ( n=5 ) was associated with a significantly higher mortality rates , 18.3 , 23.3 and 40 % , respectively ( p < 0.05 ) , and significantly lower 1-year survival rates , 50.9 , 39.1 and 20 % , respectively ( p < 0.05 ) . CONCLUSIONS The risk of more extensive resection is not balanced by improved survival in this population based series . Extending gastric resection to involve contiguous organs should be confined to highly selected cases Extended lymphadenectomy for gastric carcinoma has been associated with high mortality and morbidity rates in several multicentre r and omized trials BACKGROUND Historical data and recent studies show that st and ardised extended ( D2 ) lymphadenectomy leads to better results than st and ardised limited ( D1 ) lymphadenectomy . Based on these findings , the Dutch D1D2 trial , a nationwide prospect ively r and omised clinical trial , was undertaken to compare D2 with D1 lymphadenectomy in patients with resectable primary adenocarcinoma of the stomach . The aim of the study was to assess the effect of D2 compared with D1 surgery on disease recurrence and survival in patients treated with curative intent . METHODS Between August , 1989 , and July , 1993 , patients were entered and r and omised at 80 participating hospitals by means of a telephone call to the central data centre of the trial . The sequence of r and omisation was in blocks of six with stratification for the participating centre . Eligibility criteria were a histologically proven adenocarcinoma of the stomach without evidence of distance metastasis , age younger than 85 years , and adequate physical condition for D1 or D2 lymphadenectomy . Patients were excluded if they had previous or coexisting cancer or had undergone gastrectomy for benign tumours . Strict quality control measures for pathological assessment were implemented and monitored . Analyses were by intention to treat . This study is registered with the NCI trial register , as DUT-KWF-CKVO-8905 , EU-90003 . FINDINGS A total of 1078 patients were entered in the study , of whom 996 were eligible . 711 patients underwent the r and omly assigned treatment with curative intent ( 380 in the D1 group and 331 in the D2 group ) and 285 had palliative treatment . Data were collected prospect ively and all patients were followed up for a median time of 15.2 years ( range 6.9 - 17.9 years ) . Analyses were done for the 711 patients treated with curative intent and were according to the allocated treatment group . Of the 711 patients , 174 ( 25 % ) were alive , all but one without recurrence . Overall 15-year survival was 21 % ( 82 patients ) for the D1 group and 29 % ( 92 patients ) for the D2 group ( p=0.34 ) . Gastric-cancer-related death rate was significantly higher in the D1 group ( 48 % , 182 patients ) compared with the D2 group ( 37 % , 123 patients ) , whereas death due to other diseases was similar in both groups . Local recurrence was 22 % ( 82 patients ) in the D1 group versus 12 % ( 40 patients ) in D2 , and regional recurrence was 19 % ( 73 patients ) in D1 versus 13 % ( 43 patients ) in D2 . Patients who had the D2 procedure had a significantly higher operative mortality rate than those who had D1 ( n=32 [ 10 % ] vs n=15 [ 4 % ] ; 95 % CI for the difference 2 - 9 ; p=0.004 ) , higher complication rate ( n=142 [ 43 % ] vs n=94 [ 25 % ] ; 11 - 25 ; p<0.0001 ) , and higher reoperation rate ( n=59 [ 18 % ] vs n=30 [ 8 % ] ; 5 - 15 ; p=0.00016 ) . INTERPRETATION After a median follow-up of 15 years , D2 lymphadenectomy is associated with lower locoregional recurrence and gastric-cancer-related death rates than D1 surgery . The D2 procedure was also associated with significantly higher postoperative mortality , morbidity , and reoperation rates . Because a safer , spleen-preserving D2 resection technique is currently available in high-volume centres , D2 lymphadenectomy is the recommended surgical approach for patients with resectable ( curable ) gastric cancer . FUNDING Dutch Health Insurance Funds Council and The Netherl and s Cancer Foundation BACKGROUND Resection of the spleen en bloc with the stomach for gastric cancer is still widely performed for a curative resection ( R0 ) , but the presence of the spleen may have a favorable effect on recurrence control and survival . The hypothesis that the spleen suppresses tumor growth from minimal residual disease in the critical early postsurgical period and reduces the risk of recurrent disease was tested . PATIENTS AND METHODS Patients were included who underwent gastrectomy , with or without splenectomy , for gastric adenocarcinoma . St and ardized , strongly-defined criteria were used to accurately stratify patients , who had an extended ( D2 ) lymph node dissection , into the curative and non-curative resection groups . Limited , D1 resection confounds appropriate R-stratification and thus D1 patients were excluded . Prospect ively-defined primary endpoints were early ( within two years ) and overall recurrence and death from any cause and secondary endpoints were postsurgical risks ( morbidity , mortality ) and metastases to the splenic hilum nodes . RESULTS Overall survival for the total population studied ( n = 202 ) was better for preservation-versus-resection of the spleen among R0 patients ( p = 0.0001 ) , but not for those with non-curative resection ( p = 0.42 ) . For the R0 D2 group of patients , preservation ( n = 59 ) over resection ( n = 67 ) of the spleen , there was no significant difference in in-hospital postoperative morbidity or mortality ( 3.4 % vs. 0 % ) . At a median follow-up of 112 months , significantly the preservation of the spleen , lowered the risks of early recurrence ( HR , 0.33 ; 95 % CI , 0.16 to 0.69 ; p = 0.003 ) and death from any cause ( p = 0.009 ) after adjustment analysis . Since at baseline there was a significant imbalance of tumor stage in favor of the spleen-preservation group , we conducted a stage-stratified subgroup analysis . This treatment effect remained consistent in the subgroup analyses according to nodal and serosal status , while in multivariate analysis preservation of the spleen was an independent predictor of outcome . An overestimation of the risk for residual disease in the splenic hilum nodes in the case of spleen preservation was obtained in 94 % of splenectomized patients . CONCLUSION Our findings indicate that preservation of the spleen may be associated with a reduced risk of early and overall recurrence translated into a better survival in patients receiving curative surgery for gastric cancer . A large r and omized trial is needed to confirm this finding . Indications for splenectomy are few , being limited to those patients with advanced proximal cancers Background : In Japan , the tail and body of the pancreas are generally removed for dissection of lymph nodes along the splenic artery . A new pancreas-preserving method was developed to decrease the postoperative complications due to pancreatic resection . Patients and Methods : Between 1981 and 1989 , 110 patients were registered in a r and omized controlled trial , which included total gastrectomy plus dissection of lymph node along the splenic artery , either with ( 55 patients : Group A ) or without ( 55 : Group B ) pancreas tail resection . In Group B , the splenic artery and spleen were removed and the pancreas was preserved . There were no significant differences between the two groups in terms of sex , age , location , microscopic classification , or disease stage . The postoperative complications and survival rates were compared between the two groups . Results : The average number of dissected nodes along the splenic artery was 4.6 and 4.1 for Groups A and B , respectively . The amounts of blood loss during the operation were 994 ml and 904 ml for groups A and B , respectively . Anastomosis failure and /or pancreatic fistula occurred in nine patients in Group A ( 16 % ) and seven in Group B ( 13 % ) . One year after the operation , a glucose tolerance test showed diabetes in 6 % and impaired glucose tolerance in 33 % of patients in group A , while these findings were normal in group B. The 5-year survival rates were 80 % and 76.7 % for groups A and B , respectively . Conclusions : The pancreas-preserving method described here was superior to the more common pancreas resecting method with regard to surgical risk and postoperative glucose tolerance BACKGROUND Classic surgical treatment of upper third gastric carcinoma is based on an extended total gastrectomy , including splenectomy . The purpose of this study was to perform a prospect i ve r and omized clinical trial comparing the early and late results of total gastrectomy ( TG ) versus total gastrectomy plus splenectomy ( TGS ) . METHODS One hundred eighty-seven patients with gastric carcinoma were included . In all patients a D2 total gastrectomy was performed . During surgery they were r and omized to 1 of 2 operative options . They were monitored to their death or to 5 years later if they were alive . RESULTS Operative mortality was similar after both operations ( 3 % after TG and 4 % after TGS ) . Septic complications after surgery were higher after TGS compared with TG ( P < .04 ) . Five-year survival rates were not statistically different between groups or in subset analysis according to stage of disease . CONCLUSIONS On the basis of the results of the present prospect i ve r and omized trial , splenectomy is not necessary in early stages of disease . A low operative mortality rate ( less than 3 % ) must be achieved to obtain good long-term results A r and omized controlled trial has started in Japan to evaluate the role of splenectomy in the surgical management of gastric cancer . Patients with T2 or deeper carcinoma in the proximal third of the stomach are intra-operatively r and omized to either splenectomy or spleen preservation . Tumors invading the greater curvature of the stomach or those with apparent nodal involvement in the splenic hilum are excluded . Surgeons in 29 specialized institutions will recruit 500 patients . Endpoints are overall survival , operative morbidity , operative time and blood loss Background The survival of patients with advanced gastric cancer after D2 dissection is still poor . Asian surgeons have proposed a more radical lymph node dissection , design ated as D4 dissection , where paraaortic lymph nodes are removed in combination with D2 dissection . To evaluate the survival benefit of D4 dissection , a multi-institutional r and omized trial of D2 vs D4 gastrectomy was conducted . Methods Patients enrolled in the study had potentially curable gastric adenocarcinoma at an advanced stage . Patients were r and omized to undergo either D2 or D4 gastrectomy . Results Two hundred and ninety-three patients were registered and 269 patients were eligible ; 135 patients were allocated to the D2 group and 134 to the D4 group . Five-year survival was 52.6 % after D2 surgery and 55.0 % after D4 gastrectomy . There was no significant difference in survival between the D2 and D4 groups ( χ2 = 0.064 ; P = 0.801 ) . Hospital deaths occurred in 1 patients ( 0.7 % ) in the D2 group and 5 in the D4 group D4 gastrectomy is a more risky surgery than D2 dissection . Seven patients ( 5.2 % ) in the D2 and 15 ( 11.2 % ) in the D4 group died of causes other than gastric cancer recurrence . Sixty-three patients ( 46.7 % ) in the D2 group and 52 ( 38.8 % ) in the D4 group had disease recurrence . Conclusion Prophylactic D4 dissection is not recommended for patients with potentially curable advanced gastric cancer For patients with gastric cancer deemed curable the only treatment option is surgery , but there is disagreement about whether accompanying lymph-node dissection should be limited to the perigastric nodes ( D1 ) or should extend to regional lymph nodes outside the perigastric area ( D2 ) . We carried out a multicentre r and omised comparison of D1 and D2 dissection . 1078 patients were r and omised ( 539 to each group ) . 26 allocated D1 and 56 allocated D2 were found not to satisfy eligibility criteria ( histologically confirmed adenocarcinoma of the stomach without clinical evidence of distant metastasis ) . Each of the remainder was attended by one of eleven supervising surgeons who decided whether curative resection was possible and , if so , assisted with the allocated procedure . Among the 711 patients ( 380 D1 , 331 D2 ) judged to have curable lesions , D2 patients had a higher operative mortality rate than D1 patients ( 10 vs 4 % , p = 0.004 ) and experienced more complications ( 43 vs 25 % , p < 0.001 ) . They also needed longer postoperative hospital stays ( median 25 [ range 7 - 277 ] vs 18 [ 7 - 143 ] days , p < 0.001 ) . Morbidity and mortality differences persisted in almost all subgroup analyses . While we await survival results , D2 dissection should not be used as st and ard treatment for western patients Total gastrectomy with pancreaticosplenectomy for gastric cancer has been proposed for facilitating lymph node dissection or for resection of direct tumor invasion to the pancreas , especially for T4 lesions . Its effectiveness in improving patient survival is still controversial , and higher morbidity and mortality with this procedure have been reported in several series . Such risks to patient survival were not observed in the Japanese series . Based on a prospect i ve gastric cancer data base maintained from 1987 to 1999 in our institution , the morbidity and mortality were analyzed in our series of pancreaticosplenectomies . A total of 1,278 patients with gastric cancer received gastrectomy in our surgical unit . Of these , 127 patients underwent curative total gastrectomy with pancreaticosplenectomy in order to facilitate lymph node dissection or removal of direct tumor invasion . Operative time , postoperative hospital stay , postoperative complications , and surgical mortality were analyzed . Compared to another 201 total gastrectomies , longer mean operative time ( 7.91±2.16 hours vs. 6.67±2.01 , p<0.001 ) and postoperative hospital stay ( median , 24.5 days vs. 17 , p<0.001 ) for combined organ resection ( pancreaticosplenectomy ) were shown in this series . The major complication rate , including intraabdominal abscess , anastomotic leak , postoperative bleeding , pancreatitis/fistula , chylous leak , and general complications causing unstable vital signs ( 26.8 % vs. 11.9 % , p=0.001 ) , but not the mortality rate ( 6.3 % vs. 4.8 % , p=0.608 ) , was also shown to be higher in pancreaticosplenectomy patients . The most frequent fatal complication was intraabdominal abscess . However , more than 50 % of complications occurred in the first 40 pancreaticosplenectomies ( 1987–1991 ) ; after adequate accumulation of experience , the total complication rate ( 57.5 % vs. 35.6 % , p=0.021 ) , major complication rate ( 40 % vs. 20.7 % , p=0.022 ) , and mortality rate ( 17.5 % vs. 1.1 % , p=0.001 ) improved significantly in the remaining 87 patients ( 1991–1999 ) . We therefore conclude that total gastrectomy with pancreaticosplenectomy can be performed by experienced surgeons with acceptable risk of morbidity and mortality . RésuméLa gastrectomie totale avec splénopancréatectomie pour cancer gastrique a été proposée pour faciliter la lymphadénectomie ou pour Texérèse des lésions envahissant le pancréas , surtout en cas de lésion T4 . Si son efficience dans l’amélioration de la survie est toujours sous discussion , on a rapporté , au contraire des séries japonaises , une plus forte morbidité et mortalité , voire même une survie moindre , avec ce procédé . Basé sur une banque de données constituée prospect ivement sur le cancer gastrique entre 1987 et 1999 , la morbidité et la mortalité de la splénopancréatectomie ont été analysées chez 1278 patients gastrectomisés pour cancer gastrique . Parmi eux , 127 patients ont eu une gastrectomie totale à visée curatrice associée à une splénopancréatectomie soit pour faciliter la lymphadénectomie soit en raison d’un envahissement pancréatique . Le temps opératoire , la durée de séjour hospitalier postopératoire , les complications postopératoires et la mortalité chirurgicale ont été analysés . Comparés à 201 autres gastrectomie totales , on a observé un temps opératoire moyen ( 7.91±2.16 heures vs. 6.67±2.01 , p<0.001 ) et une durée de séjour postopératoire ( médiane , 24.5 jours vs. 17 , p<0.001 ) plus longs en cas de résection combinée ( splénopancréatectomie ) . On a observé che les patients ayant eu une splénopancréatectomie , un taux de complication majeure plus élevé y compris pour les absès intra-abdominaux , les fuites anastomotiques , l’hémorragie postopératoire , la pancréatite/fistule , les fuites chyleuses et d’autres complications responsables d’instabilité des signes vitaux ( 26.8 % vs. 11.9 % , p=0.001 ) , mais pas du taux de mortalité ( 6.3 % vs. 4.8 % , p=0.608 ) . La complication fatale la plus fréquente a été l’absès intra-abdominal . Cependant , plus de 50 % des complications se sont révélées pendant les 40 premières interventions ( 1987–1991 ) . Après une certaine expérience , ona noté une amélioration dans le taux de complications globales ( 57.5 % vs. 35.6 % , p=0.021 ) , de complications majeures ( 40 % vs. 20.7 % , p=0.022 ) et de mortalité ( 17.5 % vs. 1.1 % , p=0.001 ) chez les 87 patients suivants ( 1991- ) . Ainsi la gatrectomie totale avec splénopancréatectomie peut être réalisée avec une morbidité et une mortalité acceptables lorsqu’il agit de chirurgiens expérimentés . ResumenSe pensó que , para facilitar la disección y extirpación de las adenopatías linfáticas o incluso resecar la parte tumoral que invade el páncreas , podría realizarse , junto con la gastrectomía total , una esplenopancreatectornía , sobre todo en los cánceres gástricos T-4 , Dado que esta teoría no ha demostrado todavía su eficacia por lo que al incremento de la supervivencia se refiere y que en diversos trabajos cursa con alta mortalidad y morbilidad , ( no observada sin embargo , en las publicaciones japonesas ) , tan drástico proceder sigue siendo polémico . Se analiza nuestra experiencia basada en un estudio prospect ivo realizado entre 1987 a 1999 sobre la morbilidad y mortalidad registrada en resecciones totales gástricas , completadas o no con esplenopancreatectornía , en pacientes con cáncer gástrico . En total 1,278 pacientes fueron gastrectomizados en nuestro Servicio por cáncer de estómago . De todos ellos 127 fueron sometidos , con fines curativos , a una gastrectomía total con esplenopancreatectornía para conseguir una mayor radicalidad tanto en la resección ganglionar como en la infiltración tumoral pancreática . Analizamos : la duración de la operación , estancia hospitalaria , complicaciones postoperatorias y mortalidad ; compar and o este tratamiento radical , con 201 gastrectomies totales constatamos que : la duración de la intervención ( 7.91±2.16 vs 6.67±2.01 horas , p<0.001 ) y la estancia hospitalaria media ( 24.5 días vs 17 , p<0.001 ) fueron estadísticamente significativas . Igualmente observamos un porcentaje major de complicaciones tales como : absceso intraabdominal , dehiscencia anastomótica , hemorragia postoperatoria , pancreatitis o fístula pancreática , derrame quiloso y complicaciones generales determinantes de inestabilidad de los signos vitales ( 26.8 % vs 11.9 % , p=0.001 ) . Sin embargo , la mortalidad no fue significativamente diferente entre ambas intervenciones ( 6.3 % vs 4.8 % , p=0.608 ) . Cu and o la gastrectomía total se completa con una esplenopancreatectornía , la complicación más frecuente y de fatal evolución fue el absceso intraabdominal . Sin embargo , más del 50 % de estas complicaciones se registraron durante las 40 primeras esplenopancreatectomías ( 1987–1991 ) ; tras adquirir una experiencia adecuada en la 87 intervencionas restantes ( 1991- ) el número total de complicaciones disminuyó ( 57.5 % vs 35.6 % , p=0.021 ) ; las complicaciones graves fueron menores ( 40 % vs 20.7 % , p=0.022 ) así como la mortalidad ( 17.5 % vs 1.1 % , p=0.001 ) . Por tanto , la gastrectomía total asociada a una esplenopancreatectornía puede realizarse , por cirujanos experimentados , con una aceptable morbi-mortalidad BACKGROUND The disadvantages of D2 gastrectomy have been mostly related to splenopancreatectomy . Unlike two large European trials , we have recently showed the safety of D2 dissection with pancreas preservation in a one-arm phase I-II trial . This new r and omised trial was set up to compare post-operative morbidity and mortality and survival after D1 and D2 gastrectomy among the same experienced centres that participated into the previous trial . METHODS In a prospect i ve multicenter r and omised trial , D1 gastrectomy was compared to D2 gastrectomy . Central r and omisation was performed following a staging laparotomy in 162 patients with potentially curable gastric cancer . FINDINGS Of 162 patients r and omised , 76 were allocated to D1 and 86 to D2 gastrectomy . The two groups were comparable for age , sex , site , TNM stage of tumours , and type of resection performed . The overall post-operative morbidity rate was 13.6 % . Complications developed in 10.5 % of patients after D1 and in 16.3 % of patients after D2 gastrectomy . This difference was not statistically significant ( p<0.29 ) . Reoperation rate was 3.4 % after D2 and 2.6 % after D1 resection . Post-operative mortality rate was 0.6 % ( one death ) ; it was 1.3 % after D1 and 0 % after D2 gastrectomy . INTERPRETATION Our preliminary data confirm that in very experienced centres morbidity and mortality after extended gastrectomy can be as low as those showed by Japanese authors . They also suggest that D2 gastrectomies with pancreas preservation are not followed by significantly higher morbidity and mortality than D1 resections A r and omized comparison of D1 ( level 1 lymphadenectomy ) and D3 ( levels 1 , 2 and 3 lymphadenectomy ) dissection was performed to evaluate morbidity and effects on survival from gastric cancer BACKGROUND / AIMS The role of splenectomy in the surgical management of gastric carcinoma is controversial and there is no consensus of opinion regarding the therapeutic value of splenectomy . The aim of this study was to search for possible metastasis to lymph nodes in the splenic hilum or along the splenic artery to avoid unnecessary splenectomy and to determine its indication . METHODOLOGY The clinical records of 204 patients who underwent total gastrectomy combined with splenectomy for gastric carcinomas involving the proximal part of the stomach were analyzed . RESULTS The incidence of nodal involvement to the splenic hilum and /or along the splenic artery was 49 ( 24.0 % ) of 204 gastric carcinomas involving the proximal part of the stomach that underwent combined gastrectomy and splenectomy . The characteristics of gastric carcinoma with metastasis to these nodes included a larger tumor , deeper penetration ( T3 , 4 tumors ) , a number of lymph node metastasis , and infiltrative type . In T2 cases , all the tumors with cancerous involvement to these nodes showed intraoperative gross serosal change ) . When the tumor size was less than 40 mm , nodal metastatic rate to the splenic hilum and /or along the splenic artery was very low . CONCLUSIONS In conclusion , splenectomy should be conducted in T2 cases with gross serosal change and T3 , 4 cases . With regard to tumor size , in the cases with a tumor whose size was less than 40 mm , it is possible to preserve the spleen in most cases . In the near future , splenectomy should be clarified precisely by r and omized trials in advanced gastric carcinoma Splenectomy is often performed in patients who undergo total gastrectomy for cancer of the upper stomach . Although splenectomy facilitates lymph node dissection of the splenic hilum and recent reports advocate spleen preservation , the role of the spleen is not fully eluci date d in gastric cancer treatment . This prospect i ve r and omized study was performed to evaluate the role of the spleen in immunological function in gastric cancer patients who underwent total gastrectomy and received postoperative immunochemotherapy . Forty-five patients with gastric cancer were r and omly allocated to four groups : 1 . splenectomy without immunotherapy ( OK-432 administration ) , 2 . splenectomy with immunotherapy , 3 . spleen preservation without immunotherapy , 4 . spleen preservation with immunotherapy . Postoperative immunological function of these patients was compared among the four groups . NK cell activity of the peripheral blood lymphocytes ( PBL ) in spleen-preserved patients who received immunotherapy was significantly higher for 24 weeks after surgery than that of the splenectomized patients with and without OK-432 administration . IL-2 production of PBL in spleen-preserved patients with immunotherapy was significantly higher between 4 and 24 weeks after surgery compared with that of the splenectomized patients without immunotherapy . The results suggest that spleen preservation might be beneficial in patients with less advanced gastric cancer who receive postoperative immunochemotherapy after total gastrectomy Summary Controversy still exists on the optimal surgical resection for potentially curable gastric cancer . Much better long-term survival has been reported in retrospective/non-r and omized studies with D2 resections that involve a radical extended regional lymphadenectomy than with the st and ard D1 resections . In this paper we report the long-term survival of patients entered into a r and omized study , with follow-up to death or 3 years in 96 % of patients and a median follow-up of 6.5 years . In this prospect i ve trial D1 resection ( removal of regional perigastric nodes ) was compared with D2 resection ( extended lymphadenectomy to include level 1 and 2 regional nodes ) . Central r and omization followed a staging laparotomy . Out of 737 patients with histologically proven gastric adenocarcinoma registered , 337 patients were ineligible by staging laparotomy because of advanced disease and 400 were r and omized . The 5-year survival rates were 35 % for D1 resection and 33 % for D2 resection ( difference –2 % , 95 % CI = –12%–8 % ) . There was no difference in the overall 5-year survival between the two arms ( HR = 1.10 , 95 % CI 0.87–1.39 , where HR > 1 implies a survival benefit to D1 surgery ) . Survival based on death from gastric cancer as the event was similar in the D1 and D2 groups ( HR = 1.05 , 95 % CI 0.79–1.39 ) as was recurrence-free survival ( HR = 1.03 , 95 % CI 0.82–1.29 ) . In a multivariate analysis , clinical stages II and III , old age , male sex and removal of spleen and pancreas were independently associated with poor survival . These findings indicate that the classical Japanese D2 resection offers no survival advantage over D1 surgery . However , the possibility that D2 resection without pancreatico-splenectomy may be better than st and ard D1 resection can not be dismissed by the results of this trial BACKGROUND The aim of this study was to investigate the effects of D2 lymphadenectomy with spleen preservation on surgical outcomes in locally advanced proximal gastric cancer . METHODS Between January 2000 and December 2004 , a total of 366 patients who underwent curative total gastrectomy were studied retrospectively from a prospect ively design ed data base . RESULTS The spleen-preservation group experienced shorter operation times , a lower incidence of perioperative transfusion , and shorter postoperative hospital stays . Perioperative transfusion and splenectomy were independent risk factors for morbidity . There was no significant difference between the two groups in recurrence or cumulative survival rate when adjusted according to cancer stage . Multivariate analysis showed that tumor size , serosal invasion , and nodal metastasis were independent prognostic factors , while splenectomy was not . The cumulative survival rate in pN0-status patients was significantly higher in the spleen-preservation group , while there was no significant difference in the survival of pN1- or pN2-status patients between the two groups . CONCLUSIONS Splenectomy for lymph node dissection in proximal gastric cancer patients obviously showed poor short-surgical outcomes , but it did not affect long-term outcomes in terms of recurrence and overall survival rate . Therefore , spleen-preserving lymphadenectomy is a feasible method for radical surgery in locally advanced proximal gastric cancer |
12,153 | 28,556,176 | Lixisenatide was well tolerated , demonstrating rates of symptomatic hypoglycemia of 0.8 - 42.9 % and a very low rate of severe hypoglycemia ( < 1.5 % ) as well as no increased risk of cardiovascular events .
The most common adverse events were gastrointestinal in nature , mainly transient nausea and vomiting of mild-to-moderate severity .
Lixisenatide effectively lowers HbA1c levels in patients with T2D through a mechanism of action complementary to that of agents that mainly target FPG , with the additional benefit of weight loss . | Lixisenatide , a short-acting glucagon-like peptide-1 receptor agonist ( GLP-1 RA ) , has been available in Europe since 2013 and was recently approved in the United States for the treatment of type 2 diabetes ( T2D ) as an adjunct to diet and exercise .
The objective of this systematic review is to describe the pharmacology , pharmacokinetics , safety , and efficacy of lixisenatide in patients with T2D . | AIMS To evaluate the impact of β-cell function on the efficacy of lixisenatide , a once-daily pr and ial glucagon-like peptide-1 receptor agonist , in patients with type 2 diabetes ( T2D ) . MATERIAL S AND METHODS In this post hoc analysis , patients from the Phase 3 Get Goal -M and Get Goal -S clinical trials r and omized to lixisenatide 20μg once daily were stratified into quartiles by baseline β-cell function , as measured by the secretory units of islet in transplantation ( SUIT ) index . RESULTS Patients ( N=437 ) were distributed evenly among SUIT index quartiles 1 to 4 ( lowest to highest β-cell function ) . Clinical outcomes improved from baseline across all SUIT quartiles ; mean changes at week 24 were : glycated hemoglobin ( HbA1c ; % [ mmol/mol ] ) , -0.99 ( -10.8 ) , -0.87 ( -9.5 ) , -0.86 ( -9.4 ) , -0.83 ( -9.1 ) ; and postpr and ial plasma glucose ( PPG ; mmol/L ) , -7.9 , -5.6 , -5.5 , -4.3 ( overall effect P<0.0001 ) . Furthermore , postpr and ial glucagon was reduced in all SUIT quartiles , while insulinogenic index improved only in patients with higher baseline SUIT ( overall effect P=0.0286 ) . No severe symptomatic hypoglycemic events were reported . CONCLUSIONS Lixisenatide treatment result ed in reductions in HbA1c and PPG levels across all SUIT quartiles . This suggests that non-insulin-related actions of lixisenatide contribute to improved glycemic control in T2D AIMS To compare the efficacy and safety of once-daily pr and ial lixisenatide with placebo in type 2 diabetes mellitus ( T2DM ) insufficiently controlled by pioglitazone ± metformin . METHODS This r and omized , double-blind study included a 24-week main treatment period and a ≥52-week variable extension period . Patients were r and omized 2 : 1 to receive lixisenatide 20 µg once daily or placebo . The primary endpoint was change in glycated haemoglobin ( HbA1c ) at week 24 . RESULTS In total , 484 patients were r and omized : 323 to lixisenatide ; 161 to placebo . After 24 weeks , lixisenatide once daily significantly improved HbA1c ( -0.56 % vs. placebo ; p < 0.0001 ) and increased the proportion of patients achieving HbA1c < 7 % compared with placebo ( 52.3 % vs. 26.4 % , respectively ; p < 0.0001 ) and significantly improved fasting plasma glucose ( -0.84 mmol/l vs. placebo ; p < 0.0001 ) . There was a small decrease in body weight with lixisenatide once daily and a small increase with placebo , with no statistically significant difference between the two groups . Overall , lixisenatide once daily was well tolerated , with a similar proportion of treatment-emergent adverse events ( TEAEs ) and serious TEAEs between groups ( lixisenatide : 72.4 % and 2.5 % ; placebo : 72.7 % and 1.9 % ) . Symptomatic hypoglycaemia rates were also relatively low in both groups ( lixisenatide 3.4 % and placebo 1.2 % ) , with no severe episodes . Lixisenatide continued to be efficacious and well tolerated during the variable extension period . CONCLUSIONS Lixisenatide once daily significantly improved glycaemic control with a low risk of hypoglycaemia , and was well tolerated over 24 weeks and during the long-term , double-blind extension period in patients with T2DM insufficiently controlled on pioglitazone ± metformin OBJECTIVE To examine the efficacy and safety of lixisenatide ( 20 μg once daily , administered before the morning or evening meal ) as add-on therapy in patients with type 2 diabetes insufficiently controlled with metformin alone . RESEARCH DESIGN AND METHODS This was a 24-week , r and omized , double-blind , placebo-controlled study in 680 patients with inadequately controlled type 2 diabetes ( HbA1c 7–10 % [ 53−86 mmol/mol ] ) . Patients were r and omized to lixisenatide morning ( n = 255 ) , lixisenatide evening ( n = 255 ) , placebo morning ( n = 85 ) , or placebo evening ( n = 85 ) injections . RESULTS Lixisenatide morning injection significantly reduced mean HbA1c versus combined placebo ( mean change −0.9 % [ 9.8 mmol/mol ] vs. −0.4 % [ 4.4 mmol/mol ] ; least squares [ LS ] mean difference vs. placebo −0.5 % [ 5.5 mmol/mol ] , P < 0.0001 ) . HbA1c was significantly reduced by lixisenatide evening injection ( mean change –0.8 % [ 8.7 mmol/mol ] vs. –0.4 % [ 4.4 mmol/mol ] ; LS mean difference –0.4 % [ 4.4 mmol/mol ] , P < 0.0001 ) . Lixisenatide morning injection significantly reduced 2-h postpr and ial glucose versus morning placebo ( mean change −5.9 vs. −1.4 mmol/L ; LS mean difference −4.5 mmol/L , P < 0.0001 ) . LS mean difference in fasting plasma glucose was significant in both morning ( –0.9 mmol/L , P < 0.0001 ) and evening ( –0.6 mmol/L , P = 0.0046 ) groups versus placebo . Mean body weight decreased to a similar extent in all groups . Rates of adverse events were 69.4 % in both lixisenatide groups and 60.0 % in the placebo group . Rates for nausea and vomiting were 22.7 and 9.4 % for lixisenatide morning and 21.2 and 13.3 % for lixisenatide evening versus 7.6 and 2.9 % for placebo , respectively . Symptomatic hypoglycemia occurred in 6 , 13 , and 1 patient for lixisenatide morning , evening , and placebo , respectively , with no severe episodes . CONCLUSIONS In patients with type 2 diabetes inadequately controlled on metformin , lixisenatide 20 μg once daily administered in the morning or evening significantly improved glycemic control , with a pronounced postpr and ial effect , and was well tolerated Aim Assess the pharmacodynamics of lixisenatide once daily ( QD ) versus liraglutide QD in type 2 diabetes insufficiently controlled on metformin . Methods In this 28-day , r and omized , open-label , parallel-group , multicentre study ( NCT01175473 ) , patients ( mean HbA1c 7.3 % ) received subcutaneous lixisenatide QD ( 10 µg weeks 1–2 , then 20 µg ; n = 77 ) or liraglutide QD ( 0.6 mg week 1 , 1.2 mg week 2 , then 1.8 mg ; n = 71 ) 30 min before breakfast . Primary endpoint was change in postpr and ial plasma glucose ( PPG ) exposure from baseline to day 28 during a breakfast test meal . Results Lixisenatide reduced PPG significantly more than liraglutide [ mean change in AUC0:30–4:30h : −12.6 vs. −4.0 h·mmol/L , respectively ; p < 0.0001 ( 0:30 h = start of meal ) ] . Change in maximum PPG excursion was −3.9 mmol/l vs. −1.4 mmol/l , respectively ( p < 0.0001 ) . More lixisenatide-treated patients achieved 2-h PPG < 7.8 mmol/l ( 69 % vs. 29 % ) . Changes in fasting plasma glucose were greater with liraglutide ( −0.3 vs. −1.3 mmol/l , p < 0.0001 ) . Lixisenatide provided greater decreases in postpr and ial glucagon ( p < 0.05 ) , insulin ( p < 0.0001 ) and C-peptide ( p < 0.0001 ) . Mean HbA1c decreased in both treatment groups ( from 7.2 % to 6.9 % with lixisenatide vs. 7.4 % to 6.9 % with liraglutide ) as did body weight ( −1.6 kg vs. −2.4 kg , respectively ) . Overall incidence of adverse events was lower with lixisenatide ( 55 % ) versus liraglutide ( 65 % ) , with no serious events or hypoglycaemia reported . Conclusions Once daily prebreakfast lixisenatide provided a significantly greater reduction in PPG ( AUC ) during a morning test meal versus prebreakfast liraglutide . Lixisenatide provided significant decreases in postpr and ial insulin , C-peptide ( vs. an increase with liraglutide ) and glucagon , and better gastrointestinal tolerability than liraglutide OBJECTIVE When oral therapy for type 2 diabetes is ineffective , adding basal insulin improves glycemic control . However , when glycated hemoglobin ( HbA1c ) remains elevated because of postpr and ial hyperglycemia , the next therapeutic step is controversial . We examined the efficacy and safety of lixisenatide in patients with HbA1c still elevated after initiation of insulin glargine . RESEARCH DESIGN AND METHODS This double-blind , parallel-group trial enrolled patients with HbA1c 7–10 % despite oral therapy . Insulin glargine was added and systematic ally titrated during a 12-week run-in , after which c and i date s with fasting glucose ≤7.8 mmol/L and HbA1c 7–9 % were r and omized to lixisenatide 20 µg or placebo for 24 weeks while insulin titration continued . The primary end point was HbA1c change after r and omization . RESULTS The r and omized population ( n = 446 ) had mean diabetes duration of 9.2 years , BMI 31.8 kg/m2 , and daily glargine dosage of 44 units . HbA1c had decreased during run-in from 8.6 to 7.6 % ; adding lixisenatide further reduced HbA1c by 0.71 vs. 0.40 % with placebo ( least squares mean difference , –0.32 % ; 95 % CI , –0.46 to –0.17 ; P < 0.0001 ) . More participants attained HbA1c < 7 % with lixisenatide ( 56 vs. 39 % ; P < 0.0001 ) . Lixisenatide reduced plasma glucose 2 h after a st and ardized breakfast ( difference vs. placebo –3.2 mmol/L ; P < 0.0001 ) and had a favorable effect on body weight ( difference vs. placebo –0.89 kg ; P = 0.0012 ) . Nausea , vomiting , and symptomatic hypoglycemia < 3.3 mmol/L were more common with lixisenatide . CONCLUSIONS Adding lixisenatide to insulin glargine improved overall and postpr and ial hyperglycemia and deserves consideration as an alternative to pr and ial insulin for patients not reaching HbA1c goals with recently initiated basal insulin Aims To assess the efficacy and safety of once-daily lixisenatide versus placebo in Asian patients with type 2 diabetes insufficiently controlled on basal insulin ± sulfonylurea . Methods In this 24-week , r and omized , double-blind , placebo-controlled , parallel-group , multicentre study , participants ( mean baseline HbA1c 8.53 % ) from Japan , Republic of Korea , Taiwan and the Philippines received lixisenatide ( n = 154 ) or placebo ( n = 157 ) in a stepwise dose increase to 20 µg once daily . The primary endpoint was HbA1c change from baseline to week 24 . Results Once-daily lixisenatide significantly improved HbA1c versus placebo ( LS mean difference vs. placebo = −0.88 % [ 95%CI= −1.116 , −0.650 ] ; p < 0.0001 ) , and allowed more patients to achieve HbA1c < 7.0 % ( 35.6 vs. 5.2 % ) and ≤6.5 % ( 17.8 vs. 1.3 % ) . Lixisenatide also significantly improved 2-h postpr and ial plasma glucose and glucose excursion , average 7-point self-monitored blood glucose and fasting plasma glucose . Lixisenatide was well tolerated ; 86 % of patients on lixisenatide completed the study versus 92 % on placebo . Ten ( 6.5 % ) lixisenatide and 9 ( 5.7 % ) placebo patients experienced serious adverse events . More lixisenatide patients [ 14 ( 9.1 % ) ] discontinued for adverse events versus placebo [ 5 ( 3.2 % ) ] , mainly with gastrointestinal causes . Nausea and vomiting were reported in 39.6 and 18.2 % of patients on lixisenatide versus 4.5 and 1.9 % on placebo . Symptomatic hypoglycaemia was more frequent with lixisenatide ( 42.9 % ) versus placebo ( 23.6 % ) , but was similar between groups ( 32.6 vs. 28.3 % , respectively ) , in those not receiving sulfonylureas . No severe hypoglycaemia was reported . Conclusions In an Asian type 2 diabetes population insufficiently controlled by basal insulin ± sulfonylurea , once-daily lixisenatide significantly improved glycaemic control , with a pronounced postpr and ial effect , and was well tolerated Aims / Introduction This was a sub analysis of Japanese patients included in the glucagon-like peptide-1 receptor agonist AVE0010 in patients with type 2 diabetes mellitus for glycemic control and safety evaluation ( Get Goal -S ) study – a 24-week , r and omized , placebo-controlled study of lixisenatide in patients with type 2 diabetes mellitus inadequately controlled by sulfonylurea with or without metformin . Material s and Methods In Get Goal -S , 127 Japanese patients received the once-daily pr and ial glucagon-like peptide-1 receptor agonist lixisenatide 20 μg/day or a matching placebo . The primary outcome was change in glycated hemoglobin . Results At week 24 , lixisenatide significantly reduced mean glycated hemoglobin ( least squares mean difference vs the placebo −1.1 % [ 12 mmol/mol , P < 0.0001 ] ) , and significantly more lixisenatide patients reached glycated hemoglobin targets of < 7 % ( 53 mmol/mol ) and ≤6.5 % ( 48 mmol/mol ) vs the placebo . Lixisenatide produced statistically significant reductions in 2-h postpr and ial plasma glucose ( least squares mean difference vs the placebo −8.51 mmol/L , P < 0.0001 ) and glucose excursion vs the placebo , and significantly reduced fasting plasma glucose ( least squares mean difference vs the placebo −0.65 mmol/L , P = 0.0454 ) . Bodyweight decreased with both lixisenatide and the placebo ( least squares mean change −1.12 kg for lixisenatide , −1.02 kg for placebo ) . The overall incidence of adverse events was similar for lixisenatide and the placebo ( 84.2 and 82.4 % , respectively ) , the most frequent being gastrointestinal disorders ( 52.6 % for lixisenatide vs 29.4 % for placebo ) . The incidence of symptomatic hypoglycemia was higher with lixisenatide vs the placebo ( 17.1 and 9.8 % , respectively ) , with no cases of severe symptomatic hypoglycemia in either group . Conclusions In the Japanese sub population of the Get Goal -S study , lixisenatide produced a significant and clinical ly relevant improvement in glycated hemoglobin , with a pronounced improvement in postpr and ial plasma glucose , and a good safety and tolerability profile AIMS This 76-week , open-label , parallel-group study assessed the long-term safety of once-daily lixisenatide monotherapy in Japanese patients with type 2 diabetes mellitus . METHODS Patients were r and omized to receive lixisenatide in a 2-step or a 1-step dose-increase regimen . The primary objective was to assess the safety of lixisenatide at week 24 by a descriptive comparison of the 2- and 1-step groups . RESULTS As expected with treatment with a glucagon-like peptide-1 agonist , nausea was the most common treatment-emergent adverse event ( 2-step group : n=12/33 [ 36.4 % ] vs 1-step group : n=18/36 [ 50.0 % ] up to week 24 ) . In total , 5/33 patients ( 15.2 % ; 2-step group ) and 2/36 patients ( 5.6 % ; 1-step group ) prematurely discontinued treatment up to week 24 , mainly due to adverse events . Serious treatment-emergent adverse events occurred in 2/33 patients ( 6.1 % ; 2-step group ) versus 0/36 patients ( 0 % ; 1-step group ) up to week 24 . Symptomatic hypoglycemia occurred in 2/33 patients ( 6.1 % ; 2-step group ) versus 1/36 patients ( 2.8 % ; 1-step group ) up to week 24 , with no severe events reported . Glycated hemoglobin , fasting plasma glucose , and body weight were reduced from baseline at weeks 24 and 76 . CONCLUSION In Japanese patients with type 2 diabetes mellitus , once-daily lixisenatide monotherapy was well tolerated , with less nausea with the 2-step regimen OBJECTIVE To compare the efficacy and safety of liraglutide versus lixisenatide as add-on to metformin in patients with type 2 diabetes not achieving adequate glycemic control on metformin alone . RESEARCH DESIGN AND METHODS In this 26-week , r and omized , parallel-group , open-label trial , 404 patients were r and omized 1:1 to liraglutide 1.8 mg or lixisenatide 20 µg as add-on to metformin . Liraglutide was administered once daily at any time of the day . Lixisenatide was administered once daily within 1 h prior to the morning or evening meal . RESULTS At week 26 , liraglutide reduced HbA1c ( primary end point ) more than lixisenatide ( estimated treatment difference −0.62 % [ 95 % CI −0.8 ; −0.4 ] ; P < 0.0001 ) , with more patients reaching HbA1c < 7 % ( 53 mmol/mol ) and ≤6.5 % ( 48 mmol/mol ) versus lixisenatide ( 74.2 % and 54.6 % for liraglutide vs. 45.5 % and 26.2 % for lixisenatide ; P < 0.0001 for both ) . Liraglutide reduced fasting plasma glucose more than lixisenatide ( estimated treatment difference −1.15 mmol/L [ 95 % CI −1.5 ; −0.8 ] ; P < 0.0001 ) . Liraglutide provided greater reduction in mean 9-point self-measured plasma glucose ( P < 0.0001 ) . However , postpr and ial glucose increments were smaller with lixisenatide for the meal directly after injection compared with liraglutide ( P < 0.05 ) , with no differences between treatments across all meals . Both drugs promoted similar body weight decrease ( −4.3 kg for liraglutide , −3.7 kg for lixisenatide ; P = 0.23 ) . The most common adverse events in both groups were gastrointestinal disorders . Greater increases in pulse , lipase , and amylase were observed with liraglutide . Hypoglycemic episodes were rare and similar between the two treatments . CONCLUSIONS At the dose levels studied , liraglutide was more effective than lixisenatide as add-on to metformin in improving glycemic control . Body weight reductions were similar . Both treatments were well tolerated , with low risk of hypoglycemia and similar gastrointestinal adverse event profiles OBJECTIVE This mechanistic trial compared the pharmacodynamics and safety of lixisenatide and liraglutide in combination with optimized insulin glargine with/without metformin in type 2 diabetes ( T2D ) . RESEARCH DESIGN AND METHODS This was a multicenter , r and omized , open-label , three-arm trial comparing lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg once daily for 8 weeks in combination with insulin glargine after optimized titration . The primary end point was change from baseline to week 8 in incremental area under the postpr and ial plasma glucose curve for 4 h after a st and ardized solid breakfast ( AUC PPG0030–0430 h ) . Changes from baseline in gastric emptying , 24-h plasma glucose profile , HbA1c , fasting plasma glucose ( FPG ) , 24-h ambulatory heart rate and blood pressure , amylase and lipase levels , and adverse events ( AEs ) were also assessed . RESULTS In total , 142 patients were r and omized and treated . Lixisenatide 20 µg achieved greater reductions of AUC PPG0030−0430 h compared with liraglutide ( marginal mean [ 95 % one-sided CI ] treatment difference , −6.0 [ −7.8 ] h ⋅ mmol/L [ −108.3 ( −140.0 ) h ⋅ mg/dL ] vs. liraglutide 1.2 mg and −4.6 [ −6.3 ] h ⋅ mmol/L [ −83.0 ( −114.2 ) h ⋅ mg/dL ] vs. liraglutide 1.8 mg ; P < 0.001 for both ) , and gastric emptying was delayed to a greater extent than with liraglutide 1.2 and 1.8 mg ( P < 0.001 for treatment comparisons ) . FPG was unchanged in all treatment arms . At week 8 , mean ± SD HbA1c was 6.2 ± 0.4 % ( 44 ± 5 mmol/mol ) , 6.1 ± 0.3 % ( 44 ± 4 mmol/mol ) , and 6.1 ± 0.3 % ( 44 ± 4 mmol/mol ) for lixisenatide 20 µg and liraglutide 1.2 and 1.8 mg , respectively . At week 8 , both liraglutide doses increased marginal mean ± SE 24-h heart rate from baseline by 9 ± 1 bpm vs. 3 ± 1 bpm with lixisenatide ( P < 0.001 ) . Occurrence of symptomatic hypoglycemia was higher with lixisenatide ; gastrointestinal AEs were more common with liraglutide . Lipase levels were significantly increased from baseline with liraglutide 1.2 and 1.8 mg ( marginal mean ± SE increase 21 ± 7 IU/L for both ; P < 0.05 ) . CONCLUSIONS Lixisenatide and liraglutide improved glycemic control in optimized insulin glargine-treated T2D albeit with contrasting mechanisms of action and differing safety profiles OBJECTIVE To assess efficacy and safety of lixisenatide monotherapy in type 2 diabetes . RESEARCH DESIGN AND METHODS R and omized , double-blind , 12-week study of 361 patients not on glucose-lowering therapy ( HbA1c 7–10 % ) allocated to one of four once-daily subcutaneous dose increase regimens : lixisenatide 2-step ( 10 μg for 1 week , 15 μg for 1 week , and then 20 μg ; n = 120 ) , lixisenatide 1-step ( 10 μg for 2 weeks and then 20 μg ; n = 119 ) , placebo 2-step ( n = 61 ) , or placebo 1-step ( n = 61 ) ( placebo groups were combined for analyses ) . Primary end point was HbA1c change from baseline to week 12 . RESULTS Once-daily lixisenatide significantly improved HbA1c ( mean baseline 8.0 % ) in both groups ( least squares mean change vs. placebo : −0.54 % for 2-step , −0.66 % for 1-step ; P < 0.0001 ) . Significantly more lixisenatide patients achieved HbA1c < 7.0 % ( 52.2 % 2-step , 46.5 % 1-step ) and ≤6.5 % ( 31.9 % 2-step , 25.4 % 1-step ) versus placebo ( 26.8 % and 12.5 % , respectively ; P < 0.01 ) . Lixisenatide led to marked significant improvements of 2-h postpr and ial glucose levels and blood glucose excursions measured during a st and ardized breakfast test . A significant decrease in fasting plasma glucose was observed in both lixisenatide groups versus placebo . Mean decreases in body weight ( ∼2 kg ) were observed in all groups . The most common adverse events were gastrointestinal — nausea was the most frequent ( lixisenatide 23 % overall , placebo 4.1 % ) . Symptomatic hypoglycemia occurred in 1.7 % of lixisenatide and 1.6 % of placebo patients , with no severe episodes . Safety/tolerability was similar for the two dose regimens . CONCLUSIONS Once-daily lixisenatide monotherapy significantly improved glycemic control with a pronounced postpr and ial effect ( 75 % reduction in glucose excursion ) and was safe and well tolerated in type 2 diabetes Abstract Aims /hypothesisThe central nervous system ( CNS ) is a major player in the regulation of food intake . The gut hormone glucagon-like peptide-1 ( GLP-1 ) has been proposed to have an important role in this regulation by relaying information about nutritional status to the CNS . We hypothesised that endogenous GLP-1 has effects on CNS reward and satiety circuits . Methods This was a r and omised , crossover , placebo-controlled intervention study , performed in a university medical centre in the Netherl and s. We included patients with type 2 diabetes and healthy lean control subjects . Individuals were eligible if they were 40–65 years . Inclusion criteria for the healthy lean individuals included a BMI < 25 kg/m2 and normoglycaemia . Inclusion criteria for the patients with type 2 diabetes included BMI > 26 kg/m2 , HbA1c levels between 42 and 69 mmol/mol ( 6.0–8.5 % ) and treatment for diabetes with only oral glucose-lowering agents . We assessed CNS activation , defined as blood oxygen level dependent ( BOLD ) signal , in response to food pictures in obese patients with type 2 diabetes ( n = 20 ) and healthy lean individuals ( n = 20 ) using functional magnetic resonance imaging ( fMRI ) . fMRI was performed in the fasted state and after meal intake on two occasions , once during infusion of the GLP-1 receptor antagonist exendin 9 - 39 , which was administered to block actions of endogenous GLP-1 , and on the other occasion during saline ( placebo ) infusion . Participants were blinded for the type of infusion . The order of infusion was determined by block r and omisation . The primary outcome was the difference in BOLD signal , i.e. in CNS activation , in predefined regions in the CNS in response to viewing food pictures . Results All patients were included in the analyses . Patients with type 2 diabetes showed increased CNS activation in CNS areas involved in the regulation of feeding ( insula , amygdala and orbitofrontal cortex ) in response to food pictures compared with lean individuals ( p ≤ 0.04 ) . Meal intake reduced activation in the insula in response to food pictures in both groups ( p ≤ 0.05 ) , but this was more pronounced in patients with type 2 diabetes . Blocking actions of endogenous GLP-1 significantly prevented meal-induced reductions in bilateral insula activation in response to food pictures in patients with type 2 diabetes ( p ≤ 0.03 ) . Conclusions /interpretationOur findings support the hypothesis that endogenous GLP-1 is involved in postpr and ial satiating effects in the CNS of obese patients with type 2 diabetes . Trial registration : Clinical Trials.gov NCT 01363609 Funding The study was funded in part by a grant from Novo Nordisk Aims To evaluate the dose – response relationship of lixisenatide ( AVE0010 ) , a glucagon-like peptide-1 ( GLP-1 ) receptor agonist , in metformin-treated patients with Type 2 diabetes . Methods R and omized , double-blind , placebo-controlled , parallel-group , 13 week study of 542 patients with Type 2 diabetes inadequately controlled [ glycated haemoglobin ( HbA1c ) ≥ 7.0 and < 9.0 % ( ≥ 53 and < 75 mmol/mol ) ] on metformin ( ≥ 1000 mg/day ) treated with subcutaneous lixisenatide doses of 5 , 10 , 20 or 30 μg once daily or twice daily or placebo . The primary end-point was change in HbA1c from baseline to 13 weeks in the intent-to-treat population . Results Lixisenatide significantly improved mean HbA1c from a baseline of 7.55 % ( 59.0 mmol/mol ) ; respective mean reductions for 5 , 10 , 20 and 30 μg doses were 0.47 , 0.50 , 0.69 and 0.76 % ( 5.1 , 5.5 , 7.5 and 8.3 mmol/mol ) , on once-daily and 0.65 , 0.78 , 0.75 and 0.87 % ( 7.1 , 8.5 , 8.2 and 9.5 mmol/mol ) on twice-daily administrations vs. 0.18 % ( 2.0 mmol/mol ) with placebo ( all P < 0.01 vs. placebo ) . Target HbA1c < 7.0 % ( 53 mmol/mol ) at study end was achieved in 68 % of patients receiving 20 and 30 μg once-daily lixisenatide vs. 32 % receiving placebo ( P < 0.0001 ) . Dose-dependent improvements were observed for fasting , postpr and ial and average self-monitored seven-point blood glucose levels . Weight changes ranged from −2.0 to −3.9 kg with lixisenatide vs. −1.9 kg with placebo . The most frequent adverse event was mild-to-moderate nausea . Conclusions Lixisenatide significantly improved glycaemic control in mildly hyperglycaemic patients with Type 2 diabetes on metformin . Dose – response relationships were seen for once- and twice-daily regimens , with similar efficacy levels , with a 20 μg once-daily dose of lixisenatide demonstrating the best efficacy-to-tolerability ratio . This new , once-daily GLP-1 receptor agonist shows promise in the management of Type 2 diabetes to be defined further by ongoing long-term studies Liraglutide is a glucagon-like peptide-1 ( GLP-1 ) analog developed for type 2 diabetes . Long-term liraglutide exposure in rodents was associated with thyroid C-cell hyperplasia and tumors . Here , we report data supporting a GLP-1 receptor-mediated mechanism for these changes in rodents . The GLP-1 receptor was localized to rodent C-cells . GLP-1 receptor agonists stimulated calcitonin release , up-regulation of calcitonin gene expression , and subsequently C-cell hyperplasia in rats and , to a lesser extent , in mice . In contrast , humans and /or cynomolgus monkeys had low GLP-1 receptor expression in thyroid C-cells , and GLP-1 receptor agonists did not activate adenylate cyclase or generate calcitonin release in primates . Moreover , 20 months of liraglutide treatment ( at > 60 times human exposure levels ) did not lead to C-cell hyperplasia in monkeys . Mean calcitonin levels in patients exposed to liraglutide for 2 yr remained at the lower end of the normal range , and there was no difference in the proportion of patients with calcitonin levels increasing above the clinical ly relevant cutoff level of 20 pg/ml . Our findings delineate important species-specific differences in GLP-1 receptor expression and action in the thyroid . Nevertheless , the long-term consequences of sustained GLP-1 receptor activation in the human thyroid remain unknown and merit further investigation OBJECTIVE To provide evidence -based options on how to intensify basal insulin , we explored head-to-head pr and ial interventions in overweight patients with type 2 diabetes inadequately controlled on basal insulin glargine with or without 1–3 oral antidiabetic agents ( OADs ) . RESEARCH DESIGN AND METHODS Patients were r and omized to lixisenatide once daily or insulin glulisine given once or thrice daily , added to glargine , with or without metformin , if HbA1c remained ≥7 to ≤9 % ( ≥53 to ≤75 mmol/mol ) after 12 weeks of glargine optimization with OADs other than metformin stopped at the start of optimization . Co primary end points at 26 weeks were 1 ) noninferiority ( 95 % CI upper bound < 0.4 % [ < 4.4 mmol/mol ] ) in HbA1c reduction with lixisenatide versus glulisine once daily , and either 2a ) noninferiority in HbA1c reduction for lixisenatide versus glulisine thrice daily or 2b ) superiority in body weight change for lixisenatide versus glulisine thrice daily . Fasting and postpr and ial plasma glucose , composite efficacy/safety end points , and adverse events were also assessed . RESULTS Baseline characteristics were similar between arms ( n = 298 , diabetes and basal insulin duration of 12.2 and 3.2 years , respectively ; BMI 32.2 kg/m2 ) . HbA1c improved from 8.5 % to 7.9 % ( 69 to 63 mmol/mol ) with glargine optimization and further to 7.2 % , 7.2 % , and 7.0 % ( 55 , 55 , and 53 mmol/mol ) with lixisenatide and glulisine once daily and thrice daily , respectively ; all co primary end points were met . Symptomatic hypoglycemia and body weight were lower in lixisenatide versus glulisine patients . More gastrointestinal events occurred with lixisenatide . CONCLUSIONS Short-acting glucagon-like peptide-1 receptor agonists as add-on to basal insulin may become a preferred treatment intensification option , attaining meaningful glycemic targets with fewer hypoglycemic events without weight gain versus basal-plus or basal-bolus in uncontrolled basal insulin-treated type 2 diabetes AIMS To assess efficacy and safety of lixisenatide once-daily versus placebo in type 2 diabetes mellitus ( T2DM ) patients inadequately controlled on sulfonylurea ( SU ) ± metformin . METHODS In this r and omized , double-blind , two-arm , parallel-group , multicenter study , patients received lixisenatide 20 μg once-daily or placebo for 24 weeks in a stepwise dose increase on top of SUs ± metformin . Primary outcome was change in HbA1c from baseline to Week 24 . RESULTS Lixisenatide provided a significant reduction in HbA1c at Week 24 versus placebo ( LS mean : -0.85 % vs. -0.10 % ; p<0.0001 ) and more patients achieved HbA1c < 7.0 % ( 36.4 % vs. 13.5 % ; p<0.0001 ) . Lixisenatide significantly lowered FPG and body weight versus placebo . In breakfast meal test patients , lixisenatide reduced 2-hour PPG versus placebo ( LS mean : -111.48 vs. -3.80 mg/dL [ -6.19 vs. -0.21 mmol/L ] ; p<0.0001 ) and glucose excursion ( -94.11 vs. + 6.24 mg/dL [ -5.22 vs. + 0.35 mmol/L ] ) , and reduced 2-hour glucagon , insulin , proinsulin , and C-peptide . The percentage of AEs was 68.3 % for lixisenatide and 61.1 % for placebo ; and for SAEs : 3.5 % versus 5.6 % , respectively . Lixisenatide did not significantly increase symptomatic hypoglycemia versus placebo ( 15.3 % vs. 12.3 % , respectively ) ; one severe episode of hypoglycemia was reported with lixisenatide . CONCLUSIONS Once-daily lixisenatide significantly improved glycemic control , with a pronounced postpr and ial effect , without significant increase in symptomatic/severe hypoglycemia risk and with weight loss over 24 weeks Background : Glucagon-like peptide-1 ( GLP-1 ) receptor agonists are a relatively recent addition to the treatment options for type 2 diabetes mellitus ( T2DM ) and are administered using prefilled pen devices . Method : In this open-label task and interview-based pilot study , 3 GLP-1 receptor agonist pen devices — exenatide ( Byetta ® , Bristol-Myers Squibb/AstraZeneca ) , liraglutide ( Victoza ® , Novo Nordisk ) , and lixisenatide ( Lyxumia ® , Sanofi-Aventis)—were comparatively assessed in a r and omized order in 30 participants with T2DM for ease of use , using a series of key performance measures ( time taken to complete a series of tasks , number of user errors [ successful performance ] , and user satisfaction rating ) . Linear and logistic regression analysis was conducted for the lixisenatide and liraglutide pens versus the exenatide pen . Participants ’ mean age was 60 years ; 27 % and 20 % of the participants had visual impairments and reduced manual dexterity , respectively . Results : Tasks were completed faster ( P < .001 ) and with higher successful performance ( P = .001 ) with the lixisenatide pen than with the exenatide pen , whereas the liraglutide pen was not statistically significant versus the exenatide pen on these parameters . Overall , user satisfaction was statistically higher for the lixisenatide and liraglutide pens versus the exenatide pen ( P < .001 for both ) . Conclusions : Lixisenatide and liraglutide pens are associated with higher user satisfaction compared with the exenatide pen . In addition , the lixisenatide pen is faster and results in fewer errors than its comparator ( exenatide ) . The lixisenatide pen may therefore be a suitable choice for patients with T2DM , including older and pen device-naïve patients , and those with visual impairments and reduced manual dexterity The PDY6797 study evaluated efficacy , safety and pharmacodynamics of lixisenatide in Japanese and Caucasian patients with type 2 diabetes mellitus ( T2DM ) insufficiently controlled with sulphonylureas with/without metformin BACKGROUND Cardiovascular morbidity and mortality are higher among patients with type 2 diabetes , particularly those with concomitant cardiovascular diseases , than in most other population s. We assessed the effects of lixisenatide , a glucagon-like peptide 1-receptor agonist , on cardiovascular outcomes in patients with type 2 diabetes who had had a recent acute coronary event . METHODS We r and omly assigned patients with type 2 diabetes who had had a myocardial infa rct ion or who had been hospitalized for unstable angina within the previous 180 days to receive lixisenatide or placebo in addition to locally determined st and ards of care . The trial was design ed with adequate statistical power to assess whether lixisenatide was noninferior as well as superior to placebo , as defined by an upper boundary of the 95 % confidence interval for the hazard ratio of less than 1.3 and 1.0 , respectively , for the primary composite end point of cardiovascular death , myocardial infa rct ion , stroke , or hospitalization for unstable angina . RESULTS The 6068 patients who underwent r and omization were followed for a median of 25 months . A primary end-point event occurred in 406 patients ( 13.4 % ) in the lixisenatide group and in 399 ( 13.2 % ) in the placebo group ( hazard ratio , 1.02 ; 95 % confidence interval [ CI ] , 0.89 to 1.17 ) , which showed the noninferiority of lixisenatide to placebo ( P<0.001 ) but did not show superiority ( P=0.81 ) . There were no significant between-group differences in the rate of hospitalization for heart failure ( hazard ratio in the lixisenatide group , 0.96 ; 95 % CI , 0.75 to 1.23 ) or the rate of death ( hazard ratio , 0.94 ; 95 % CI , 0.78 to 1.13 ) . Lixisenatide was not associated with a higher rate of serious adverse events or severe hypoglycemia , pancreatitis , pancreatic neoplasms , or allergic reactions than was placebo . CONCLUSIONS In patients with type 2 diabetes and a recent acute coronary syndrome , the addition of lixisenatide to usual care did not significantly alter the rate of major cardiovascular events or other serious adverse events . ( Funded by Sanofi ; ELIXA Clinical Trials.gov number , NCT01147250 . ) BACKGROUND This study assessed the efficacy and safety of the once-daily glucagon-like peptide-1 receptor agonist , lixisenatide , in Asian patients with type 2 diabetes mellitus inadequately controlled on metformin ± sulfonylurea . METHODS In this 24-week , double-blind , placebo-controlled , multinational study , patients were r and omized to lixisenatide 20 µg once daily or placebo . The primary endpoint was absolute change in glycated haemoglobin ( HbA1c ) from baseline to week 24 . RESULTS A total of 391 patients were r and omized . Lixisenatide significantly reduced HbA1c levels compared with placebo ( LS mean difference : -0.36 % , p = 0.0004 ) . A significantly higher proportion of lixisenatide-treated patients achieved HbA1c targets of < 7 % ( p = 0.003 ) and ≤6.5 % ( p = 0.001 ) versus placebo . Lixisenatide was associated with a statistically significant reduction in 2-h postpr and ial plasma glucose after a st and ardized breakfast versus placebo ( LS mean difference : -4.28 mmol/L , p < 0.0001 ) and a significant reduction in fasting plasma glucose ( p = 0.0109 ) . There was no difference in weight loss versus placebo , with a modest reduction in body weight reported for both groups ( lixisenatide : -1.50 kg , placebo : -1.24 kg ; p = 0.296 ) . The incidence of treatment-emergent adverse events ( TEAEs ) was 64.3 % with lixisenatide versus 47.4 % with placebo , with serious TEAEs reported in 1.5 % versus 2.1 % of patients , respectively . The most common TEAE in the lixisenatide group was nausea ( 16.3 % vs 2.6 % with placebo ) . The incidence of symptomatic hypoglycaemia was 5.6 % with lixisenatide treatment and 2.6 % with placebo ( p = 0.1321 ) , with no severe symptomatic hypoglycaemia events reported . CONCLUSIONS In Asian patients with type 2 diabetes mellitus insufficiently controlled on metformin ± sulfonylurea , lixisenatide significantly improved glycaemic control and was well tolerated during the 24-week study Abstract Background Lixisenatide is a once‐daily , pr and ial , short‐acting glucagon‐like peptide‐1 receptor agonist . Its main antidiabetic effect is to delay gastric emptying to control postpr and ial plasma glucose excursions . The dose – response relationship of the integrated insulinotropic and gastrostatic response to lixisenatide in healthy volunteers after a st and ardized liquid meal was investigated . Methods Twenty healthy subjects received acetaminophen 1000 mg with a st and ardized liquid meal 60 min after a single subcutaneous injection of placebo or lixisenatide 2.5 , 5 , 10 or 20 µg in r and omized order separated by a 2‐ to 7‐day washout . Acetaminophen pharmacokinetics served as a surrogate to assess rate of gastric emptying . Postpr and ial plasma glucose , insulin , C‐peptide and glucagon were assessed for 5 h after the meal test , and lixisenatide pharmacokinetics were determined for 6 h. Results After lixisenatide administration and prior to the st and ardized meal , insulin and C‐peptide transiently increased , while fasting plasma glucose decreased in a dose‐dependent manner . After the meal , postpr and ial plasma glucose , insulin and C‐peptide were dose proportionally reduced with lixisenatide versus placebo for up to 6 h. Compared with placebo , glucagon levels were transiently lower after any lixisenatide dose , with more sustained reductions after the meal and no apparent dose‐related trends . Acetaminophen absorption was significantly reduced and delayed compared with placebo for lixisenatide doses ≥5 µg and demonstrated dose‐dependent slowing of gastric emptying . Lixisenatide displayed near dose‐proportional exposure , with gastrointestinal events increasing with dose . Conclusions Lixisenatide reduced fasting plasma glucose via stimulation of glucose‐dependent insulin release and controlled postpr and ial plasma glucose by delaying gastric emptying , demonstrating it to be a valuable option for overall glycaemic control . Copyright © 2015 John Wiley & Sons , AIMS The aim of this study is to explore whether administration timing affects glycaemic control by lixisenatide once-daily in type 2 diabetes mellitus ( T2DM ) . METHODS A phase IIIb , open-label , 1:1 r and omized , active-controlled , 24-week multicentre study of T2DM patients inadequately controlled on metformin was conducted . Patients were administered lixisenatide before breakfast or the main meal . The primary endpoint was change from baseline at week 24 in glycated haemoglobin ( HbA1c ) . Other endpoints : changes in body weight , fasting plasma glucose ( FPG ) , 7-point self-monitored plasma glucose ( SMPG ) and Diabetes Treatment Satisfaction Question naire status ( DTSQs ) score . Adverse events ( AEs ) were monitored . RESULTS Mean change in HbA1c from baseline at week 24 was -0.65 % ( -7.1mmol/mol ; main meal ) and -0.74 % ( -8.1mmol/mol ; breakfast ) . Mean changes in FPG , body weight and DTSQs score were comparable between groups . The mean change in body weight ( kg ) was -2.60 ( main meal ) and -2.80 ( breakfast group ) . The 7-point SMPG profiles showed greatest reductions in postpr and ial glucose after the meal at which lixisenatide was administered , with a residual effect seen on the subsequent meal . AE rates were similar between groups , including gastrointestinal AEs . CONCLUSIONS Lixisenatide before the main meal was noninferior to lixisenatide before breakfast in patients insufficiently controlled on metformin . Lixisenatide treatment allows flexibility in administration timing Incretin hormone analogs such as glucagon-like peptide-1 ( GLP-1 ) receptor agonists have emerged as promising new options for the treatment of type 2 diabetes mellitus ( T2DM ) , targeting several of its pathophysiological traits , including reduced insulin sensitivity , inadequate insulin secretion , and loss of β-cell mass ( BCM ) . This article describes the semi-mechanistic modeling of lixisenatide dose-response over time using fasting plasma glucose ( FPG ) , fasting serum insulin ( FSI ) and glycated hemoglobin ( HbA1c ) data from two Phase II and four Phase III clinical trials , for a total of 2470 T2DM patients . Previously published models for FPG , FSI , and BCM as well as HbA1c were adapted and exp and ed to describe the available data . The model incorporated aspects describing disease progression , st and ard-of-care , FPG-dependent and -independent HbA1c synthesis , and covariate effects of body size , race , and sex . The final model described lixisenatide effects on β-cell responsiveness , insulin sensitivity and FPG-independent HbA1c synthesis , was able to describe the observed FPG , FSI , and HbA1c data accurately , and was successful in predicting data from an unseen Phase III clinical study OBJECTIVE Counterregulatory responses are critical to prevent hypoglycemia in subjects with type 2 diabetes . This is particularly important in insulin-treated patients . This study explored the effect of the glucagon-like peptide 1 receptor agonist lixisenatide on the hormonal counterregulatory responses to insulin-induced hypoglycemia when added to basal insulin therapy in subjects with type 2 diabetes . RESEARCH DESIGN AND METHODS The study was a single-center , double-blind , r and omized , placebo-controlled crossover study involving 18 subjects with type 2 diabetes ( 11 males ) with a mean age of 55 years , diabetes duration of 12 years , HbA1c level of 7.7 % , fasting blood glucose ( FBG ) concentration of 9.7 mmol/L , and a BMI of 33 kg/m2 , who were treated with basal insulin ( mean duration 7 years , daily dose 39 units/day ) and metformin ( mean daily dose 2.1 g ) . Subjects received treatment with lixisenatide or placebo for 6 weeks in r and om order , with a 4-week washout period in between . After 6 weeks of treatment , subjects underwent a two-step hyperinsulinemic hypoglycemic clamp at 3.5 and 2.8 mmol/L. RESULTS After 6 weeks of treatment , HbA1c and FBG levels were lower after lixisenatide therapy than after placebo therapy . At the hypoglycemic level of 3.5 mmol/L , glucagon and epinephrine levels were significantly lower during lixisenatide treatment than during placebo treatment , whereas at 2.8 mmol/L glucagon and epinephrine levels did not differ between the subjects . Cortisol , pancreatic polypeptide , and norepinephrine levels did not differ significantly between the treatments . CONCLUSIONS Glucagon and epinephrine levels are reduced by lixisenatide at a concentration of 3.5 mmol/L , but their counterregulatory responses to deep hypoglycemia at a concentration of 2.8 mmol/L are sustained during treatment with lixisenatide in combination with basal insulin |
12,154 | 28,848,456 | RESULTS Deficits in BD-I compared to healthy controls ( HC ) were in executive function , attention span and verbal memory .
Deficits in TLE compared to HC were in executive function and memory .
In the pre- to post-surgical comparisons , verbal memory in left temporal lobe ( LTL ) and , less consistently , visuospatial memory in right temporal lobe ( RTL ) epilepsy declined following surgery .
TLE studies typically examined a narrow range of known temporal lobe-mediated neuropsychological functions , particularly verbal and visuospatial memory .
CONCLUSION Both disorders exhibit deficits in executive function and verbal memory suggestive of both frontal and temporal lobe involvement .
However , deficits in TLE are measured pre- to post-surgery and not controlled at baseline pre-surgery . | BACKGROUND Bipolar disorder ( BD ) and temporal lobe epilepsy ( TLE ) overlap in domains including epidemiology , treatment response , shared neurotransmitter involvement and temporal lobe pathology .
Comparison of cognitive function in both disorders may indicate temporal lobe mediated processes relevant to BD .
This systematic review examines neuropsychological test profiles in euthymic bipolar disorder type I ( BD-I ) and pre-surgical TLE and compares experimental design s used . | The objective was to carry out a pilot study exploring memory outcome in patients with temporal lobe epilepsy ( TLE ) and low- grade tumour . A prospect i ve study using a competence-related memory assessment was carried out in the Laboratory of Neuropsychology , Epilepsy Center and Neurosurgical Department of the “ C. Besta ” National Neurological Institute in 24 TLE patients undergoing surgical resection for left ( n=12 ) or right ( n=12 ) low- grade tumours and 36 healthy subjects . Patients underwent mesial or lateral temporal lobe lesionectomy . Neuropsychological tests exploring verbal and visual short-term memory , learning , delayed recall and ability to control interference in memory were applied . Before and after surgery , significant verbal impairment was present in left TLE patients compared to controls and right TLE patients , and visual deficits were present in both groups compared to controls . After surgery , there was no significant decrease in mean verbal or visual memory scores related to the operated side . Some memory abilities subserved by the contralateral temporal lobe improved . Postoperative memory scores were related to preoperative scores , side of operation , age and education . In patients with TLE and low- grade tumour , temporal lobe surgery does not necessarily induce memory deficits . Improvement of memory abilities subserved by the unoperated temporal lobe may be expected BACKGROUND Although manic episodes reportedly contribute to cognitive deficits in bipolar I disorder , the contribution of depressive episodes is poorly research ed . AIMS We investigated the impact of depressive episodes on cognitive function early in the course of bipolar I disorder . METHOD A total of 68 patients and 38 controls from the Systematic Treatment Optimization Programme for Early Mania ( STOP-EM ) first-episode mania programme were examined . We conducted ( a ) a cross-sectional analysis of the impact of prior depressive episodes on baseline cognitive function and ( b ) a prospect i ve analysis assessing the contribution of depression recurrence within 1 year following a first episode of mania on cognitive functioning . RESULTS The cross-sectional analysis showed no significant differences between patients with past depressive episodes compared with those without , on overall or individual domains of cognitive function ( all P>0.09 ) . The prospect i ve analysis failed to reveal a significant group × time interaction for cognitive decline from baseline to 1 year ( P = 0.99 ) in patients with a recurrence of depressive episodes compared with those with no recurrence . However , impaired verbal memory at baseline was associated with a depression recurrence within 1 year . CONCLUSIONS Although deficits in all domains of cognitive function are seen in patients early in the course of bipolar disorder , depressive episodes do not confer additional burden on cognitive function . However , poorer verbal memory may serve as a marker for increased susceptibility to depression recurrence early in the course of illness Volumetric MRI studies based on manual labeling of selected anatomical structures have provided in vivo evidence that brain abnormalities associated with temporal lobe epilepsy ( TLE ) extend beyond the hippocampus . Voxel-based morphometry ( VBM ) is a fully automated image analysis technique allowing identification of regional differences in gray matter ( GM ) and white matter ( WM ) between groups of subjects without a prior region of interest . The purpose of this study was to determine whole-brain GM and WM changes in TLE and to investigate the relationship between these abnormalities and clinical parameters . We studied 85 patients with pharmacologically intractable TLE and unilateral hippocampal atrophy and 47 age- and sex-matched healthy control subjects . The seizure focus was right sided in 40 patients and left sided in 45 . Student 's t test statistical maps of differences between patients ' and controls ' GM and WM concentrations were obtained using a general linear model . A further regression against duration of epilepsy , age of onset , presence of febrile convulsions , and secondary generalized seizures was performed with the TLE population . Voxel-based morphometry revealed that GM pathology in TLE extends beyond the hippocampus involving other limbic areas such as the cingulum and the thalamus , as well as extralimbic areas , particularly the frontal lobe . White matter reduction was found only ipsilateral to the seizure focus , including the temporopolar , entorhinal , and perirhinal areas . This pattern of structural changes is suggestive of disconnection involving preferentially frontolimbic pathways in patients with pharmacologically intractable TLE PURPOSE We previously showed a reduction in the volume of the entorhinal cortex ( EC ) ipsilateral to the seizure focus in patients with intractable temporal lobe epilepsy ( TLE ) . The purpose of this study was to examine the specificity of EC atrophy in epilepsy . METHODS We performed volumetric measurement of the EC on high-resolution magnetic resonance imaging ( MRI ) in patients with TLE ( n = 70 ) , extratemporal lobe epilepsy ( ETE ; n = 18 ) , and idiopathic generalized epilepsy ( IGE ; n = 20 ) . EC volumes of epilepsy patients were compared with those of 48 age- and sex-matched normal controls . Within the TLE group , 63 patients were selected prospect ively with hippocampal atrophy ipsilateral to the seizure focus . The remaining seven patients were chosen retrospectively based on normal volumetric MRI of the hippocampus and amygdale , as well as normal histopathologic examination of the resected tissue . RESULTS Compared with normal controls , EC volume was smaller ipsilateral but not contralateral to the seizure focus in patients with TLE ( p < 0.001 ) . No difference in the EC volumes ipsilateral and contralateral to the seizure focus was seen in patients with ETE and IGE compared with normal controls . The individual analysis showed that the EC was atrophic in 73 % of TLE patients with hippocampal atrophy . Three of the seven TLE patients with normal volumetric MRI of the hippocampus and amygdala and normal histopathologic examination had EC atrophy ipsilateral to the seizure focus . In no patient with ETE or IGE was the EC found to be atrophic . CONCLUSIONS EC atrophy ipsilateral to the seizure focus appears to be specific to mesial temporal lobe structural damage associated with TLE OBJECTIVE The goal of the work described here was to evaluate relationships among resection volume , seizure outcome , and cognitive morbidity after temporal lobectomy for intractable epilepsy . METHODS Thirty patients with mesial temporal sclerosis were evaluated pre- and postoperatively with the Wechsler Adult Intelligence Scale III , Wechsler Memory Scale III , and three-dimensional coronal spoiled gradient recall acquisition MRI . Preoperative whole-brain volumes were calculated with Statistical Parametric Mapping . Resection volume was calculated by manual tracing . Systat was used for statistical analysis . RESULTS All resections included the temporal tip , at least 1 cm of the superior temporal gyrus , and 3 to 5 cm of the middle and inferior temporal gyri . Left were significantly smaller than right temporal resections . Seizure-free patients had significantly larger resections . Immediate verbal memory was significantly worse after left temporal lobectomy . Surgical outcome and resection volume did not affect postoperative neuropsychological results . CONCLUSIONS Dominant temporal lobe resections are associated with immediate verbal memory deficits . Larger resection volume was associated with improved seizure control but not worse cognitive outcome Objective : To assess naming and recognition of faces of familiar famous people in patients with epilepsy before and after anterior temporal lobectomy ( ATL ) . Methods : Color photographs of famous people were presented for naming and description to 63 patients with temporal lobe epilepsy ( TLE ) either before or after ATL and to 10 healthy age- and education-matched controls . Results : Spontaneous naming of photographed famous people was impaired in all patient groups , but was most abnormal in patients who had undergone left ATL . When allowed to demonstrate knowledge of the famous faces through verbal descriptions , rather than naming , patients with left TLE , left ATL , and right TLE improved to normal levels , but patients with right ATL were still impaired , suggesting a new deficit in identifying famous faces . Naming of famous people was related to naming of other common objects , verbal memory , and perceptual discrimination of faces . Recognition of the identity of pictured famous people was more related to visuospatial perception and memory . Conclusions : Lesions in anterior regions of the right temporal lobe impair recognition of the identities of familiar faces , as well as the learning of new faces . Lesions in the left temporal lobe , especially in anterior regions , disrupt access to the names of known people , but do not affect recognition of the identities of famous faces . Results are consistent with the hypothesized role of lateralized anterior temporal lobe structures in facial recognition and naming of unique entities Two hundred and ninety epilepsy surgery patients completed the Hospital Anxiety and Depression Scale and were assessed on a list learning task preoperatively and 1 year postoperatively . Deterioration and improvement in verbal memory were determined using reliable change indices ( RCIs ) at 80 and 90 % confidence limits . Almost one third of patients ( 27 % ) experienced a deterioration in verbal learning . The number of left temporal lobectomy patients who had deteriorated outnumbered the right temporal lobectomy patients by 2:1 . Significant improvements in verbal learning were seen in 21 % of the right temporal lobectomy group and 10 % of the left temporal lobectomy group . Patients who were seizure-free postoperatively were not more likely to experience a postoperative deterioration or improvement in memory than those who continued to experience seizures . No significant relationships were found between subjective ratings of postoperative memory function and objective indices of change . Reliable , objective indices of postoperative deterioration in memory function may bear little relation to the patient 's subjective experience . This should be considered when statistical predictions are used as the basis of preoperative counseling We studied the effects on verbal and nonverbal memory of anterior temporal lobe ( ATL ) surgery for epilepsy in 91 patients ( 46 men , 45 women ) , all of whom had left-hemisphere dominance for speech . Patients were divided into four groups according to sex and laterality of the excision . The memory tasks were administered shortly before surgery , 6 months postoperatively , and at a 2-year follow-up . Test scores were su bmi tted to repeated- measures analyses of variance . We found that men treated with left temporal resection declined significantly in long-delay verbal memory after surgery , whereas no clear pre- to postoperative sex differences were found with respect to other verbal memory scores . Only the results on long-delay verbal memory confirm previous findings , showing a greater vulnerability of verbal memory to left ATL surgery in men than in women . Women with left temporal excisions obtained particularly poor scores on a long-delay nonverbal memory test preoperatively , but improved their performance on this test significantly after surgery . The seemingly gradual improvement during the 2-year follow-up suggests a plastic process A number of studies have shown visuospatial memory deficits following anterior temporal lobectomy ( ATL ) in the right , nondominant temporal lobe ( RATL ) . The current study examines 26 patients with intractable temporal lobe epilepsy who underwent ATL in either the right ( RATL , n = 16 ) or left temporal lobe ( LATL , n = 10 ) on two tests of facial memory abilities , the Wechsler Memory Scale-III ( WMS-III ) Faces subtest and the Graduate Hospital Facial Memory Test ( FMT ) . Repeated measures ANOVA on the FMT indicated a significant main effect of side of surgery . The RATL group performed significantly below the LATL group overall . Both groups showed a slight , but non-significant , improvement in performance from pre- to postsurgery on the FMT immediate memory , likely due to practice effects . Repeated measures ANOVA on the WMS-III Faces subtest revealed a significant interaction of group ( RATL vs. LATL ) by delay ( immediate vs. delayed ) . Overall , the LATL group showed an improvement in recognition scores from immediate to delayed memory , whereas the RATL group performed similarly at both immediate and delayed testing . No effects of surgery were noted on the WMS-III . Following initial data analysis the WMS-III Faces I and II data were re-scored using the scoring suggested by Holdnack and Delis ( 2003 ) , earlier in this issue . Repeated measures ANOVA revealed a trend toward significance in the three-way interaction of group ( RATL vs. LATL ) × time of testing ( pre- versus postop ) × delay ( immediate vs. delayed memory ) . On the Faces I subtest , both the RATL and LATL groups showed a decline from preoperative to postoperative testing . However , on Faces II the LATL group showed an increase in performance from preoperative to postoperative testing , while the RALT group showed a decline in performance from preoperative to postoperative testing . While the FMT appears to be superior to the WMS-III Faces subtest in identifying deficits in facial memory prior to and following RATL , the application of the scoring methodology presented by Holdnack and Delis earlier in this issue does serve to increase the clinical utility of the WMS-III Faces subtest in this population The relationship between preoperative ability levels and postoperative changes in cognitive function was examined among 23 left ( LTL ) and 19 right ( RTL ) temporal lobectomy patients using a battery of memory , language , and visuospatial tasks administered approximately 3 months before surgery and at 6 months follow-up . Higher preoperative performances on the memory and language measures were associated with larger decrements in postsurgical scores among the LTL patients . The RTL group showed no consistent relationship between preoperative ability levels and subsequent postsurgical cognitive changes . Based on the present data , we constructed baserate tables for the Wechsler Memory Scale-Revised indicating the likelihood of measurable gains or losses in memory as a function of presurgical ability level for patients undergoing LTL . While tentative , these data provide a useful and practical guide for counseling prospect i ve epilepsy patients of the attendant cognitive risks of LTL The authors examined the neural and cognitive bases for sex differences in verbal memory in 57 patients who underwent left anterior temporal lobectomy ( ATL ) for the treatment of intractable seizures . On the California Verbal Learning Test ( D. C. Delis , J. H. Kramer , E. Kaplan , & B. A. Ober , 1987 ) , women recalled more words than men both before and after surgery , regardless of the extent of hippocampal damage . Extent of hippocampal sclerosis was related to memory loss in both men and women . Women 's superiority in verbal memory appears to result in part from their use of an efficient encoding strategy . Women were more likely than men to use semantic clustering both before and after ATL , and sex differences in word recall were attenuated after scores were adjusted for semantic clustering . There was no effect of ATL on semantic clustering . Taken together , these results suggest that sex differences in verbal memory are not due to differences in the integrity of the left hippocampus Previous research has shown that the degree of verbal memory decline following left anterior temporal lobectomy ( ATL ) is inversely related to the extent of neuronal dropout in resected left hippocampus . The goal of this investigation was to clarify further the nature of the free recall impairment and to determine the relative contribution of verbal retrieval and encoding processes . Seventy-six patients who underwent left ( n = 46 ) or right ( n = 30 ) ATL were classified according to the presence or absence of hippocampal sclerosis and pre- to postoperative changes in free recall , cued recall and recognition memory for verbal material were examined . Surgically induced free recall impairments were selectively associated with resection of nonsclerotic left hippocampus and represented a 29 - 35 % decline in verbal learning ability . These free recall deficits were due to postoperative impairment in verbal encoding efficiency , not retrieval difficulties . Assessment of false positive recognition errors indicated that resection of nonsclerotic left hippocampus selectively impaired the ability to encode stimulus uniqueness within correct semantic fields . The clinical and theoretical significance of these results are discussed This study represents the first prospect i ve controlled investigation of preoperative versus postoperative ( 6 months ) language function in patients who underwent partial resection of the dominant ( n = 15 ) or nondominant ( n = 14 ) anterior temporal lobe for treatment of medically refractory epilepsy . Language dominance was confirmed by in tracarotid sodium amytal test . Thirteen of the 15 patients undergoing anterior temporal lobectomy of the dominant hemisphere were operated on under local anesthesia in order to map language and memory functions intraoperatively . Using a st and ardized language /aphasia battery , we found a significant trend of worse preoperative language function in patients with dominant hemisphere temporal lobe foci in comparison to patients with nondominant foci . Following anterior temporal lobectomy , neither group showed any significant losses in language function , whereas the dominant hemisphere temporal lobe group showed significant improvement in receptive language comprehension and associative verbal fluency PURPOSE To assess outcomes of language , verbal memory , cognitive efficiency and mental flexibility , mood , and quality of life ( QOL ) in a prospect i ve , multicenter pilot study of Gamma Knife radiosurgery ( RS ) for mesial temporal lobe epilepsy ( MTLE ) . METHODS RS , r and omized to 20 Gy or 24 Gy comprising 5.5 - 7.5 ml at the 50 % isodose volume , was performed on mesial temporal structures of patients with unilateral MTLE . Neuropsychological evaluations were performed at preoperative baseline , and mean change scores were described at 12 and 24 months postoperatively . QOL data were also available at 36 months . KEY FINDINGS Thirty patients were treated and 26 were available for the final 24-month neuropsychological evaluation . Language ( Boston Naming Test ) , verbal memory ( California Verbal Learning Test and Logical Memory subtest of the Wechsler Memory Scale-Revised ) , cognitive efficiency and mental flexibility ( Trail Making Test ) , and mood ( Beck Depression Inventory ) did not differ from baseline . QOL scores improved at 24 and 36 months , with those patients attaining seizure remission by month 24s accounting for the majority of the improvement . SIGNIFICANCE The serial changes in cognitive outcomes , mood , and QOL are unremarkable following RS for MTLE . RS may provide an alternative to open surgery , especially in those patients at risk of cognitive impairment or who desire a noninvasive alternative to open surgery |
12,155 | 17,416,718 | Interventions were multifaceted with the majority demonstrating significant improvements in clinical outcomes , behavioral outcomes , and diabetes-related knowledge .
Culturally competent interventions have the potential to improve outcomes in Hispanic adults with type 2 diabetes .
However , improvements were modest and attrition was moderate to high in many studies . | Culturally competent interventions have been developed to improve outcomes for Hispanic adults with type 2 diabetes .
The purpose of this systematic review is to synthesize the research on culturally competent interventions for this vulnerable population . | OBJECTIVES We sought to determine the effects of a community-based , culturally tailored diabetes lifestyle intervention on risk factors for diabetes complications among African Americans and Latinos with type 2 diabetes . METHODS One hundred fifty-one African American and Latino adults with diabetes were recruited from 3 health care systems in Detroit , Michigan , to participate in the Racial and Ethnic Approaches to Community Health ( REACH ) Detroit Partnership diabetes lifestyle intervention . The curriculum , delivered by trained community residents , was aim ed at improving dietary , physical activity , and diabetes self-care behaviors . Baseline and postintervention levels of diabetes-specific quality -of-life , diet , physical activity , self-care knowledge and behaviors , and hemoglobin A1C were assessed . RESULTS There were statistically significant improvements in postintervention dietary knowledge and behaviors and physical activity knowledge . A statistically significant improvement in A1C level was achieved among REACH Detroit program participants ( P<.0001 ) compared with a group of patients with diabetes in the same health care system in which no significant changes were observed ( P=.160 ) . CONCLUSIONS A culturally tailored diabetes lifestyle intervention delivered by trained community residents produced significant improvement in dietary and diabetes self-care related knowledge and behaviors as well as important metabolic improvements Background : The prevalence of type 2 diabetes and diabetesrelated morbidity and mortality is higher among low-income Hispanics when compared to that of Whites . However , little is known about how to effectively promote self-management in this population . Purpose : The objectives were first to determine the feasibility of conducting a r and omized clinical trial of an innovative self-management intervention to improve metabolic control in low-income Spanish-speaking individuals with type 2 diabetes and second to obtain preliminary data of possible intervention effects . Methods : Participants for this pilot study were recruited from a community health center , an elder program , and a community-wide data base developed by the community health center , in collaboration with other agencies serving the community , by surveying households in the entire community . Participants were r and omly assigned to an intervention ( n = 15 ) or a control ( n = 10 ) condition . Assessment s were conducted at baseline and at 3 months and 6 months postr and omization . The intervention consisted of 10 group sessions that targeted diabetes knowledge , attitudes , and self-management skills through culturally specific and literacysensitive strategies . The intervention used a cognitivebehavioral theoretical framework . Results : Recruitment rates at the community health center , elder program , and community registry were 48 % , 69 % , and 8 % , respectively . Completion rates for baseline , 3-month , and 6-month assessment s were 100 % , 92 % , and 92 % , respectively . Each intervention participant attended an average of 7.8 out of 10 sessions , and as a group the participants showed high adherence to intervention activities ( 93 % turned in daily logs , and 80 % self-monitored glucose levels at least daily ) . There was an overall Group × Time interaction ( p = .02 ) indicating group differences in glycosylated hemoglobin over time . The estimated glycosylated hemoglobin decrease at 3 months for the intervention group was −0.8 % ( 95 % confidence intervals = −1.1 % , −0.5 % ) compared with the change in the control group ( p = .02 ) . At 6 months , the decrease in the intervention group remained significant , −0.85 % ( 95 % confidence intervals = −1.2 , −0.5 ) , and the decrease was still significantly different from that of the controls ( p = .005 ) . There was a trend toward increased physical activity in the intervention group as compared to that of the control group ( p = .11 ) and some evidence ( nonsignificant ) of an increase in blood glucose self-monitoring in the intervention participants but not the control participants . Adjusting for baseline depressive scores , we oberved a significant difference in depressive symptoms between intervention participants and control participants at the 3-month assessment ( p = .02 ) . Conclusions : Low-income Spanish-speaking Hispanics are receptive to participate in diabetes-related research . This study shows that the pilot-tested diabetes self-management program is promising and warrants the conduct of a r and omized clinical trial Purpose The purpose of this study was to evaluate the community-based Chronic Disease Self-management Program ( CDSMP ) and the Spanish- language version ( Tom and o Control de Su Salud ) programs as delivered in setting s along the Texas/New Mexico/Mexico border . The programs had proven effective in r and omized trials , and the authors wished to determine if they would be as effective when administered by others to different population s. Methods The El Paso Diabetes Association administered the CDSMP and Tom and o to 445 persons with chronic illness ( two thirds with diabetes ) in Texas , New Mexico , and Mexico . Four-month and 1-year outcomes were compared to baseline using t tests of change scores . Regression models were used to test whether baseline demographics and self-efficacy were associated with positive outcomes of the programs . Results Participants showed improvements in health behaviors , health status , and self-efficacy at both 4 month and 1 year . Baseline self-efficacy and 4-month change in self-efficacy were significantly associated with improved 1- year outcomes . Conclusions The CDSMP and Tom and o are effective when used in setting s other than that of the original study for population s other than those for which they were initially developed PURPOSE Few culturally competent health programs have been design ed for Mexican Americans , a group that bears a disproportionate burden of Type 2 diabetes . In Starr County , a Texas-Mexico border community , investigators design ed and tested a culturally competent intervention aim ed at improving the health of this target population . The purpose of this article is to describe the development process of this diabetes education and support group intervention . METHODS The development stages were ( 1 ) community assessment , ( 2 ) intervention design , ( 3 ) selection or development of outcomes , ( 4 ) pilot testing , and ( 5 ) a r and omized clinical investigation . RESULTS Focus group participants identified knowledge deficits regarding diabetes and self-management strategies , and suggested characteristics of an effective intervention for Mexican Americans . Outcome measures included metabolic control indicators , a newly developed knowledge instrument , and an existing health belief instrument . Preliminary analyses indicated that the intervention was successful in significantly improving metabolic control in the target population . CONCLUSIONS Developing successful diabetes interventions for minority groups requires a number of stages , careful planning , assessment of cultural characteristics of the target population , and a systematic approach to implementation OBJECTIVE The objective of this study was to compare two diabetes self-management interventions design ed for Mexican Americans : " extended " ( 24 h of education , 28 h of support groups ) and " compressed " ( 16 h of education , 6 h of support groups ) . Both interventions were culturally competent regarding language , diet , social emphasis , family participation , and incorporating cultural beliefs . RESEARCH DESIGN AND METHODS We recruited 216 persons between 35 and 70 years of age diagnosed with type 2 diabetes > /=1 year . Intervention groups of eight participants and eight support persons were r and omly assigned to the compressed or extended conditions . The interventions differed in total number of contact hours over the year-long intervention period , with the major difference being the number of support group sessions held . The same information provided in the educational sessions of the extended intervention was compressed into fewer sessions , thus providing more information during each group meeting . RESULTS The interventions were not statistically different in reducing HbA(1c ) ; however , both were effective . A " dosage effect " of attendance was detected with the largest HbA(1c ) reductions achieved by those who attended more of the extended intervention . For individuals who attended > /=50 % of the intervention , baseline to 12-month HbA(1c ) change was -0.6 percentage points for the compressed group and -1.7 percentage points for the extended group . CONCLUSIONS Both culturally competent diabetes self-management education interventions were effective in promoting improved metabolic control and diabetes knowledge . A dosage effect was evident ; attending more sessions result ed in greater improvements in metabolic control OBJECTIVE To determine the effects of a culturally competent diabetes self-management intervention in Mexican Americans with type 2 diabetes . RESEARCH DESIGN AND METHODS A prospect i ve , r and omized , repeated measures study was conducted on the Texas-Mexico border in Starr County . A total of 256 r and omly selected individuals with type 2 diabetes between 35 and 70 years of age , diagnosed with type 2 diabetes after 35 years of age , and accompanied by a family member or friend were included . The intervention consisted of 52 contact hours over 12 months and was provided by bilingual Mexican American nurses , dietitians , and community workers . The intervention involved 3 months of weekly instructional sessions on nutrition , self-monitoring of blood glucose , exercise , and other self-care topics and 6 months of biweekly support group sessions to promote behavior changes . The approach was culturally competent in terms of language , diet , social emphasis , family participation , and incorporation of cultural health beliefs . Outcomes included indicators of metabolic control ( HbA(1c ) and fasting blood glucose ) , diabetes knowledge , and diabetes-related health beliefs . RESULTS Experimental groups showed significantly lower levels of HbA(1c ) and fasting blood glucose at 6 and 12 months and higher diabetes knowledge scores . At 6 months , the mean HbA(1c ) of the experimental subjects was 1.4 % below the mean of the control group ; however , the mean level of the experimental subjects was still high ( > 10 % ) . CONCLUSIONS This study confirms the effectiveness of culturally competent diabetes self-management education on improving health outcomes of Mexican Americans , particularly for those individuals with HbA(1c ) levels > 10 % BACKGROUND Type 2 diabetes affects approximately 8 percent of adults in the United States . Some risk factors -- elevated plasma glucose concentrations in the fasting state and after an oral glucose load , overweight , and a sedentary lifestyle -- are potentially reversible . We hypothesized that modifying these factors with a lifestyle-intervention program or the administration of metformin would prevent or delay the development of diabetes . METHODS We r and omly assigned 3234 nondiabetic persons with elevated fasting and post-load plasma glucose concentrations to placebo , metformin ( 850 mg twice daily ) , or a lifestyle-modification program with the goals of at least a 7 percent weight loss and at least 150 minutes of physical activity per week . The mean age of the participants was 51 years , and the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) was 34.0 ; 68 percent were women , and 45 percent were members of minority groups . RESULTS The average follow-up was 2.8 years . The incidence of diabetes was 11.0 , 7.8 , and 4.8 cases per 100 person-years in the placebo , metformin , and lifestyle groups , respectively . The lifestyle intervention reduced the incidence by 58 percent ( 95 percent confidence interval , 48 to 66 percent ) and metformin by 31 percent ( 95 percent confidence interval , 17 to 43 percent ) , as compared with placebo ; the lifestyle intervention was significantly more effective than metformin . To prevent one case of diabetes during a period of three years , 6.9 persons would have to participate in the lifestyle-intervention program , and 13.9 would have to receive metformin . CONCLUSIONS Lifestyle changes and treatment with metformin both reduced the incidence of diabetes in persons at high risk . The lifestyle intervention was more effective than metformin Background In light of health disparities and the growing prevalence of chronic disease , there is a need for community-based interventions that improve health behaviors and health status . These interventions should be based on existing theory . Objective This study aim ed to evaluate the health and utilization outcomes of a 6-week community-based program for Spanish speakers with heart disease , lung disease , or type 2 diabetes . Method The treatment participants in this study ( n = 327 ) took a 6-week peer-led program . At 4 months , they were compared with r and omized wait-list control subjects ( n = 224 ) using analyses of covariance . The outcomes for all the treatment participants were assessed at 1 year , as compared with baseline scores ( n = 271 ) using t-tests . Results At 4 months , the participants , as compared with usual-care control subjects , demonstrated improved health status , health behavior , and self-efficacy , as well as fewer emergency room visits ( p < .05 ) . At 1 year , the improvements were maintained and remained significantly different from baseline condition . Conclusions This community-based program has the potential to improve the lives of Hispanics with chronic illness while reducing emergency room use OBJECTIVE To improve clinical diabetes care , patient knowledge , and treatment satisfaction and to reduce health-adverse culture-based beliefs in underserved and underinsured population s with diabetes . RESEARCH DESIGN AND METHODS A total of 153 high-risk patients with diabetes recruited from six community clinic sites in San Diego County , California were enrolled in a nurse case management ( NCM ) and peer education/empowerment group . Baseline and 1-year levels of HbA(1c ) , lipid parameters , systolic and diastolic blood pressure , knowledge of diabetes , culture-based beliefs in ineffective remedies , and treatment satisfaction were prospect ively measured . The NCM and peer education/empowerment group was compared with 76 individuals in a matched control group ( CG ) derived from patients referred but not enrolled in Project Dulce . RESULTS After 1 year in Project Dulce , the NCM and peer education/empowerment group had significant improvements in HbA(1c ) ( 12.0 - 8.3 % , P < 0.0001 ) , total cholesterol ( 5.82 - 4.86 mmol/l , P < 0.0001 ) , LDL cholesterol ( 3.39 - 2.79 mmol/l , P < 0.0001 ) , and diastolic blood pressure ( 80 - 76 mmHg , P < 0.009 ) , which were significantly better than in the CG , in which no significant changes were noted . Accepted American Diabetes Association st and ards of diabetes care , knowledge of diabetes ( P = 0.024 ) , treatment satisfaction ( P = 0.001 ) , and culture-based beliefs ( P = 0.001 ) were also improved . CONCLUSIONS A novel , culturally appropriate , community-based , nurse case management/peer education diabetes care model leads to significant improvement in clinical diabetes care , self-awareness , and underst and ing of diabetes in underinsured population Two objectives were established for this study : 1 ) to assess the impact of a culturally specific , intensive diabetes education program on dietary patterns , and 2 ) to assess nutrient consumption relative to the Recommended Dietary Allowances . The study population consisted of elderly Mexican Americans with diabetes living in Harlingen and Brownsville , Texas . The experimental group ( n=78 ) participated in an intense , 2-hour nutrition education session , while the control group ( n=74 ) did not . The education session was conducted for groups of eight subjects via videotapes and interactive discussion . All groups experienced significant weight loss except the women in the experimental group . After the education program , however , the experimental women had increased the percentage of calories consumed daily from carbohydrate . Mean calcium consumption was substantially less than the RDA in all groups , and inadequate amounts of ascorbic acid and vitamin A often were consumed . Intensive , frequent , long-term follow-up appears essential for more sustained results OBJECTIVE To examine the effects of patient choice between two education curriculums that emphasized either the st and ard or nutritional management of type 2 diabetes on class attendance and other outcomes among a mostly Hispanic patient population . RESEARCH DESIGN AND METHODS A total of 596 patients with type 2 diabetes were r and omly assigned to either a choice or no choice condition . Patients in the choice condition were allowed to choose their curriculum , while patients in the no choice condition were r and omly assigned to one of the two curriculums . Outcomes were assessed at baseline and at a 6-month follow-up . RESULTS When given a choice , patients chose the nutrition curriculum almost four times more frequently than the st and ard curriculum . Contrary to our hypothesis , however , patients who had a choice did not significantly increase their attendance rates or demonstrate improvements in other diabetes outcomes compared with patients who were r and omly assigned to the two curriculums . Patients in the nutrition curriculum had significantly lower serum cholesterol at a 6-month follow-up , whereas patients in the st and ard curriculum had significant improvements in glycemic control . Of the r and omized patients , 30 % never attended any classes ; the most frequently cited reasons for nonattendance were socioeconomic . Hispanic patients , however , were just as likely as non-Hispanic patients to attend classes and participate at the follow-up . Patients who attended all five classes of either curriculum significantly increased their diabetes knowledge , gained less weight , and reported improved physical functioning compared with patients who did not attend any classes . CONCLUSIONS Although providing patients with a choice in curriculums at the introductory level did not improve outcomes , differential improvements were noted between patients who attended curriculums with different content emphasis . We suggest that diabetes education programs should provide the opportunity for long-term , repetitive contacts to exp and on the modest gains achieved at the introductory level , as well as provide more options to match individual needs and interests and to address socioeconomic barriers to participation The purpose of this article was to characterize the origins of the United States Hispanic population and discuss the implication s of these origins in the context of diabetes risk . Particular attention was focused on the genetic origins of the three major U.S. Hispanic groups , i.e. , Mexican Americans , Puerto Ricans , and Cubans . The U.S. Census figures provided basic demographic information . Genetic marker data for ancestral population s were taken from a review of the literature and compendia . Genetic marker data for the Puerto Rican and Cuban population s were extracted from the literature . Genetic markers determined on ∼ 1000 r and omly selected Mexican Americans from Starr County , Texas , were taken as representative of the Mexican-American population . The Hispanic population is the second largest and fastest growing minority in the U.S. Estimates of the Hispanic population in 1988 indicated some 19.4 million residents , of whom 62 % were classified as Mexican , 13 % as Puerto Rican , and the remaining 25 % as Cubans and others . Various lines of evidence can be used to characterize the Hispanic population and its origins . These include ethnohistory , self- assessment of ancestry , surname distributions , speech and cultural characteristics , quantitative traits , and genetic structure . Genetic data were used to estimate the contribution of putative ancestral population s to the contemporary gene pool . For Mexican Americans , 31 % of the contemporary gene pool is estimated to be Native American derived , whereas 61 and 8 % are Spanish and African derived , respectively . In Puerto Rico , the percentage of contributions of Spanish , Native American , and African admixture to the population are 45 , 18 , and 37 % , respectively . For Cuba , the parallel estimates are 62 , 18 , and 20 % . The high frequency of Native American-derived genes in the contemporary Hispanic population predict a higher frequency of non-insulin-dependent diabetes mellitus ( NIDDM ) under the assumption that genes are important in NIDDM etiology . Our results are consistent with the finding of the significant role of genes in determining risk OBJECTIVE To determine the effect of a bicultural community health worker ( CHW ) on completion of diabetes education in an inner-city Hispanic patient population and to evaluate the impact of completion of the education program on patient knowledge , self-care behaviors , and glycemic control . RESEARCH DESIGN AND METHODS Patients were r and omized into CHW intervention and non-CHW intervention groups . All patients received individualized , comprehensive diabetes education from a certified diabetes nurse educator after baseline demographic information , diabetes knowledge , diabetes self-care practice s , and glycohemoglobin levels were assessed . Rates of education program completion were determined . Diabetes knowledge , self-care practice s , and glycohemoglobin levels were reassessed at program completion and at a later postprogram follow-up medical appointment and compared to baseline . Logistic regression analysis and the Mantel-Haenszel χ2 statistic were used to determine the effect of the CHW assignment on program completion . Analyses of covariance were performed with end-of-treatment behavior scores , knowledge scores , and glycohemoglobin levels as outcome variables , controlling for baseline values and testing for the effect of CHW assignment . RESULTS Of 64 patients enrolled in the study , 40 ( 63 % ) completed and 24 ( 37 % ) dropped out before completing the diabetes education program . Of the patients having CHW intervention , 80 % completed the education program , compared with 47 % of patients without CHW intervention ( P = 0.01 ) . “ Dropouts ” were younger ( age 47.5 ± 12.5 years [ mean ± SD ] ) compared with patients who completed the program ( 55.9 ± 9.9 years ) ( P = 0.004 ) . Dropout status showed no significant relationship to educational level achieved or literacy level . For the program “ completers , ” knowledge levels and selected self-care practice s significantly improved , and glycohemoglobin levels improved from a baseline level of 11.7 % to 9.9 % at program completion ( P = 0.004 ) and 9.5 % at the postprogram follow-up ( P < 0.001 ) . The effect of the CHW assignment on program completion , controlling for financial status and language spoken , was extremely robust ( P = 0.007 ) . The effect of the CHW on knowledge , self-care behavior , or glycohemoglobin outcome variables was not statistically significant . CONCLUSIONS These findings suggest that intervention with a bicultural CHW improved rates of completion of a diabetes education program in an inner-city Hispanic patient population irrespective of literacy or educational levels attained . Our data further suggests that completion of individualized diabetes educational strategies leads to improved patient knowledge , self-care behaviors , and glycemic control |
12,156 | 30,131,714 | Combining training of muscle strength and cardiorespiratory fitness within a training cycle could increase athletic performance more than single-mode training .
However , the physiological effects produced by each training modality could also interfere with each other , improving athletic performance less than single-mode training .
In conclusion , CT is more effective than single-mode ET or ST in improving selected measures of physical fitness and athletic performance in youth .
Specifically , CT compared with ET improved athletic performance in children and particularly adolescents .
Finally , CT was more effective than ST in improving muscle power in youth | Because anthropometric , physiological , and biomechanical differences between young and adult athletes can affect the responses to exercise training , young athletes might respond differently to concurrent training ( CT ) compared with adults .
Thus , the aim of the present systematic review with meta- analysis was to determine the effects of concurrent strength and endurance training on selected physical fitness components and athletic performance in youth . | Abstract Makhlouf , I , Castagna , C , Manzi , V , Laurencelle , L , Behm , DG , and Chaouachi , A. Effect of sequencing strength and endurance training in young male soccer players . J Strength Cond Res 30(3 ) : 841–850 , 2016—This study examined the effects of strength and endurance training sequence ( strength before or after endurance ) on relevant fitness variables in youth soccer players . Fifty-seven young elite-level male field soccer players ( 13.7 ± 0.5 years ; 164 ± 8.3 cm ; 53.5 ± 8.6 kg ; body fat ; 15.6 ± 3.9 % ) were r and omly assigned to a control ( n = 14 , CG ) and 3 experimental training groups ( twice a week for 12 weeks ) strength before ( SE , n = 15 ) , after ( ES , n = 14 ) or on alternate days ( ASE , n = 14 ) with endurance training . A significant ( p = 0.001 ) intervention main effect was detected . There were only trivial training sequence differences ( ES vs. SE ) for all variables ( p > 0.05 ) . The CG showed large squat 1 repetition maximum ( 1RM ) and medium sprint , change of direction ability , and jump improvements . ASE demonstrated a trivial difference in endurance performance with ES and SE ( p > 0.05 ) . Large to medium greater improvements for SE and ES were reported compared with ASE for sprinting over 10 and 30 m ( p < 0.02 ) . The SE squat 1RM was higher than in ASE ( moderate , p < 0.02 ) . Postintervention differences between ES and SE with CG fitness variables were small to medium ( p ⩽ 0.05 ) except for a large SE advantage with the Yo-Yo intermittent recovery test ( p < 0.001 , large ) . This study showed no effect of intrasession training sequence on soccer fitness-relevant variables . However , combining strength and endurance within a single training session provided superior results vs. training on alternate days . Concurrent training may be considered as an effective and safe training method for the development of the prospect i ve soccer player Abstract Amaro , NM , Marinho , DA , Marques , MC , Batalha , N , and Morouço , PG . Effects of dry-l and strength and conditioning programs in age group swimmers . J Strength Cond Res 31(9 ) : 2447–2454 , 2017—Even though dry-l and S&C training is a common practice in the context of swimming , there are countless uncertainties over its effects in performance of age group swimmers . The objective was to investigate the effects of dry-l and S&C programs in swimming performance of age group swimmers . A total of 21 male competitive swimmers ( 12.7 ± 0.7 years ) were r and omly assigned to the Control group ( n = 7 ) and experimental groups GR1 and GR2 ( n = 7 for each group ) . Control group performed a 10-week training period of swim training alone , GR1 followed a 6-week dry-l and S&C program based on sets and repetitions plus a 4-week swim training program alone and GR2 followed a 6-week dry-l and S&C program focused on explosiveness , plus a 4-week program of swim training alone . Results for the dry-l and tests showed a time effect between week 0 and week 6 for vertical jump ( p < 0.01 ) in both experimental groups , and for the GR2 ball throwing ( p < 0.01 ) , with moderate to strong effect sizes . The time × group analyses showed that for performance in 50 m , differences were significant , with the GR2 presenting higher improvements than their counterparts ( F = 4.156 ; p = 0.007 ; = 0.316 ) at week 10 . Concluding , the results suggest that 6 weeks of a complementary dry-l and S&C training may lead to improvements in dry-l and strength . Furthermore , a 4-week adaptation period was m and atory to achieve beneficial transfer for aquatic performance . Additional benefits may occur if coaches plan the dry-l and S&C training focusing on explosiveness Purpose To compare the effects of strength training versus ski-ergometer training on double-poling gross efficiency ( GE ) , maximal speed ( Vmax ) , peak oxygen uptake ( $ $ \dot{V}{\text{O } } _ { { 2 { \text{peak}}}}$$V˙O2peak ) for elite male and female junior cross-country skiers . Methods Thirty-three elite junior cross-country skiers completed a 6-week training-intervention period with two additional 40-min training sessions per week . The participants were matched in pairs and within each pair r and omly assigned to either a strength-training group ( STR ) or a ski-ergometer-training group ( ERG ) . Before and after the intervention , the participants completed three treadmill roller-skiing tests to determine GE , Vmax , and $ $ \dot{V}{\text{O } } _ { { 2 { \text{peak}}}}$$V˙O2peak . Mixed between-within subjects analysis of variance ( ANOVA ) was conducted to evaluate differences between and within groups . Paired sample s t tests were used as post hoc tests to investigate within-group differences . Results Both groups improved their Vmax and $ $ \dot{V}{\text{O } } _ { { 2 { \text{peak}}}}$$V˙O2peak expressed absolutely ( all P < 0.01 ) . For the gender-specific sub-groups , it was found that the female skiers in both groups improved both Vmax and $ $ \dot{V}{\text{O } } _ { { 2 { \text{peak}}}}$$V˙O2peak expressed absolutely ( all P < 0.05 ) , whereas the only within-group differences found for the men were improvements of Vmax in the STR group . No between-group differences were found for any of the investigated variables . Conclusions Physiological and performance-related variables of importance for skiers were improved for both training regimes . The results demonstrate that the female skiers ’ physiological adaptations to training , in general , were greater than those of the men . The magnitude of the physiological adaptations was similar for both training regimes Age-related processes in the neuromuscular and the somatosensory system are responsible for decreases in maximal and explosive force production capacity and deficits in postural control . Thus , the objectives of this study were to investigate the effects of resistance training on strength performance and on postural control in seniors . Forty healthy seniors ( 67+/-1 yrs ) participated in this study . Subjects were r and omly assigned to a resistance training ( n=20 ) and a control group ( n=20 ) . Resistance training for the lower extremities lasted for 13 weeks at 80 % of the one repetition maximum . Pre and post tests included the measurement of maximal isometric leg extension force with special emphasis on the early part of the force-time-curve and the assessment of static ( functional reach test ) and dynamic ( t and em walk test , platform perturbation ) postural control . Resistance training result ed in an enhanced strength performance with increases in explosive force exceeding those in maximal strength . Improved performances in the functional reach and in the t and em walk test were observed . Resistance training did not have an effect on the compensation of platform perturbations . Increases in strength performance can primarily be explained by an improved neural drive of the agonist muscles . The inconsistent effect of resistance training on postural control may be explained by heterogeneity of testing methodology or by the incapability of isolated resistance training to improve postural control Abstract .Previous research has reported that plyometric training improves running economy ( RE ) and ultimately distance-running performance , although the exact mechanism by which this occurs remains unclear . This study examined whether changes in running performance result ing from plyometric training were related to alterations in lower leg musculotendinous stiffness ( MTS ) . Seventeen male runners were pre- and post-tested for lower leg MTS , maximum isometric force , rate of force development , 5-bound distance test ( 5BT ) , counter movement jump ( CMJ ) height , RE , V˙O2max , lactate threshold ( Thla ) , and 3-km time . Subjects were r and omly split into an experimental ( E ) group which completed 6 weeks of plyometric training in conjunction with their normal running training , and a control ( C ) group which trained as normal . Following the training period , the E group significantly improved 3-km performance ( 2.7 % ) and RE at each of the tested velocities , while no changes in V˙O2max or Thla were recorded . CMJ height , 5BT , and MTS also increased significantly . No significant changes were observed in any measures for the C group . The results clearly demonstrated that a 6-week plyometric programme led to improvements in 3-km running performance . It is postulated that the increase in MTS result ed in improved RE . We speculate that the improved RE led to changes in 3-km running performance , as there were no corresponding alterations in V˙O2max or Thla Underlying mechanisms of prepubescent strength gains following resistance training are speculative . The purpose of this investigation was to determine the effects of 8 wk of resistance training on muscular strength , integrated EMG amplitude ( IEMG ) , and arm anthropometrics of prepubescent youth . Sixteen subjects ( 8 males , 8 females ) were r and omly assigned to trained or control groups . All subjects ( mean age = 10.3 yr ) were of prepubertal status according to the criteria of Tanner . The trained group performed three sets ( 7 - 11 repetitions ) of bicep curls with dumbbells three times per week for 8 wk . Pre- and posttraining measurements included isotonic and isokinetic strength of the elbow flexors , arm anthropometrics , and IEMG of the biceps brachii . Planned comparisons for a 2 x 2 ( group by test ) ANOVA model were used for data analysis . Significant isotonic ( 22.6 % ) and isokinetic ( 27.8 % ) strength gains were observed in the trained group without corresponding changes in arm circumference or skinfolds . The IEMG amplitude increased 16.8 % ( P < 0.05 ) . The control group did not demonstrate any significant changes in the parameters measured . Early gains in muscular strength result ing from resistance training prepubescent children may be attributed to increased muscle activation PURPOSE Heavy-resistance training and plyometric training offer distinct physiological and neuromuscular adaptations that could enhance running economy and , consequently , distance-running performance . To date , no studies have examined the effect of combining the two modes of training on running economy or performance . METHODS Fifty collegiate male and female cross-country runners performed a 5-km time trial and a series of laboratory-based tests to determine aerobic , anthropometric , biomechanical , and neuromuscular characteristics . Thereafter , each athlete participated in a season of six to eight collegiate cross-country races for 13 wk . After the first 4 wk , athletes were r and omly assigned to either heavy-resistance or plyometric plus heavy-resistance training . Five days after completing their final competition , runners repeated the same set of laboratory tests . We also estimated the effects of the intervention on competition performance throughout the season using athletes of other teams as controls . RESULTS Heavy-resistance training produced small-moderate improvements in peak speed , running economy , and neuromuscular characteristics relative to plyometric resistance training , whereas changes in biomechanical measures favored plyometric resistance training . Men made less gains than women in most tests . Both treatments had possibly harmful effects on competition times in men ( mean = 0.5 % ; 90 % confidence interval = ±1.2 % ) , but there may have been benefit for some individuals . Both treatments were likely beneficial for all women ( -1.2 % ; ±1.3 % ) , but heavy-resistance training was possibly better than plyometric resistance training . CONCLUSIONS The changes in laboratory-based parameters related to distance-running performance were consistent with the changes in competition times for women but only partly for men . Our data indicate that women should include heavy-resistance training in their programs , but men should be cautious about using it in season until more research establishes whether certain men are positive or negative responders OBJECTIVES To compare the impact of short term training with resistance plus plyometric training ( RT+P ) or electromyostimulation plus plyometric training ( EMS+P ) on explosive force production in elite volleyball players . DESIGN Sixteen elite volleyball players of the first German division participated in a training study . METHODS The participants were r and omly assigned to either the RT+P training group ( n=8 ) or the EMS+P training group ( n=8 ) . Both groups participated in a 5-week lower extremity exercise program . Pre and post tests included squat jumps ( SJ ) , countermovement jumps ( CMJ ) , and drop jumps ( DJ ) on a force plate . The three-step reach height ( RH ) was assessed using a custom-made vertec apparatus . Fifteen m straight and lateral sprint ( S15s and S15l ) were assessed using photoelectric cells with interims at 5 m and 10 m. RESULTS RT+P training result ed in significant improvements in SJ ( + 2.3 % ) and RH ( + 0.4 % ) performance . The EMS+P training group showed significant increases in performance of CMJ ( + 3.8 % ) , DJ ( + 6.4 % ) , RH ( + 1.6 % ) , S15l ( -3.8 % ) and after 5 m and 10 m of the S15s ( -2.6 % ; -0.5 % ) . The comparison of training-induced changes between the two intervention groups revealed significant differences for the SJ ( p=0.023 ) in favor of RT+P and for the S15s after 5 m ( p=0.006 ) in favor of EMS+P. CONCLUSIONS The results indicate that RT+P training is effective in promoting jump performances and EMS+P training increases jump , speed and agility performances of elite volleyball players PURPOSE To quantify the effects of a 12-wk isolated core-training program on 50-m front-crawl swim time and measures of core musculature functionally relevant to swimming . METHODS Twenty national-level junior swimmers ( 10 male and 10 female , 16±1 y , 171±5 cm , 63±4 kg ) participated in the study . Group allocation ( intervention [ n=10 ] , control [ n=10 ] ) was based on 2 preexisting swim-training groups who were part of the same swimming club but trained in different groups . The intervention group completed the core training , incorporating exercises targeting the lumbopelvic complex and upper region extending to the scapula , 3 times/wk for 12 wk . While the training was performed in addition to the normal pool-based swimming program , the control group maintained their usual pool-based swimming program . The authors made probabilistic magnitude-based inferences about the effect of the core training on 50-m swim time and functionally relevant measures of core function . RESULTS Compared with the control group , the core-training intervention group had a possibly large beneficial effect on 50-m swim time ( -2.0 % ; 90 % confidence interval -3.8 to -0.2 % ) . Moreover , it showed small to moderate improvements on a timed prone-bridge test ( 9.0 % ; 2.1 - 16.4 % ) and asymmetric straight-arm pull-down test ( 23.1 % ; 13.7 - 33.4 % ) , and there were moderate to large increases in peak EMG activity of core musculature during isolated tests of maximal voluntary contraction . CONCLUSION This is the first study to demonstrate a clear beneficial effect of isolated core training on 50-m front-crawl swim performance Background : Deficits in static and particularly dynamic postural control and force production have frequently been associated with an increased risk of falling in older adults . Objective : The objectives of this study were to investigate the effects of salsa dancing on measures of static/dynamic postural control and leg extensor power in seniors . Methods : Twenty-eight healthy older adults were r and omly assigned to an intervention group ( INT , n = 14 , age 71.6 ± 5.3 years ) to conduct an 8-week progressive salsa dancing programme or a control group ( CON , n = 14 , age 68.9 ± 4.7 years ) . Static postural control was measured during one-legged stance on a balance platform and dynamic postural control was obtained while walking on an instrumented walkway . Leg extensor power was assessed during a countermovement jump on a force plate . Results : Programme compliance was excellent with participants of the INT group completing 92.5 % of the dancing sessions . A tendency towards an improvement in the selected measures of static postural control was observed in the INT group as compared to the CON group . Significant group × test interactions were found for stride velocity , length and time . Post hoc analyses revealed significant increases in stride velocity and length , and concomitant decreases in stride time . However , salsa dancing did not have significant effects on various measures of gait variability and leg extensor power . Conclusion : Salsa proved to be a safe and feasible exercise programme for older adults accompanied with a high adherence rate . Age-related deficits in measures of static and particularly dynamic postural control can be mitigated by salsa dancing in older adults . High physical activity and fitness/mobility levels of our participants could be responsible for the nonsignificant findings in gait variability and leg extensor power Purpose Strength training activities have consistently been shown to improve running economy ( RE ) and neuromuscular characteristics , such as force-producing ability and maximal speed , in adult distance runners . However , the effects on adolescent ( < 18 yr ) runners remains elusive . This r and omized control trial aim ed to examine the effect of strength training on several important physiological and neuromuscular qualities associated with distance running performance . Methods Participants ( n = 25 , 13 female , 17.2 ± 1.2 yr ) were paired according to their sex and RE and r and omly assigned to a 10-wk strength training group ( STG ) or a control group who continued their regular training . The STG performed twice weekly sessions of plyometric , sprint , and resistance training in addition to their normal running . Outcome measures included body mass , maximal oxygen uptake ( V˙O2max ) , speed at V˙O2max , RE ( quantified as energy cost ) , speed at fixed blood lactate concentrations , 20-m sprint , and maximal voluntary contraction during an isometric quarter-squat . Results Eighteen participants ( STG : n = 9 , 16.1 ± 1.1 yr ; control group : n = 9 , 17.6 ± 1.2 yr ) completed the study . The STG displayed small improvements ( 3.2%–3.7 % ; effect size ( ES ) , 0.31–0.51 ) in RE that were inferred as “ possibly beneficial ” for an average of three submaximal speeds . Trivial or small changes were observed for body composition variables , V˙O2max and speed at V˙O2max ; however , the training period provided likely benefits to speed at fixed blood lactate concentrations in both groups . Strength training elicited a very likely benefit and a possible benefit to sprint time ( ES , 0.32 ) and maximal voluntary contraction ( ES , 0.86 ) , respectively . Conclusions Ten weeks of strength training added to the program of a postpubertal distance runner was highly likely to improve maximal speed and enhances RE by a small extent , without deleterious effects on body composition or other aerobic parameters BACKGROUND AND PURPOSE Assessment of the quality of r and omized controlled trials ( RCTs ) is common practice in systematic review s. However , the reliability of data obtained with most quality assessment scales has not been established . This report describes 2 studies design ed to investigate the reliability of data obtained with the Physiotherapy Evidence Data base ( PEDro ) scale developed to rate the quality of RCTs evaluating physical therapist interventions . METHOD In the first study , 11 raters independently rated 25 RCTs r and omly selected from the PEDro data base . In the second study , 2 raters rated 120 RCTs r and omly selected from the PEDro data base , and disagreements were resolved by a third rater ; this generated a set of individual rater and consensus ratings . The process was repeated by independent raters to create a second set of individual and consensus ratings . Reliability of ratings of PEDro scale items was calculated using multirater kappas , and reliability of the total ( summed ) score was calculated using intraclass correlation coefficients ( ICC [ 1,1 ] ) . RESULTS The kappa value for each of the 11 items ranged from.36 to.80 for individual assessors and from.50 to.79 for consensus ratings generated by groups of 2 or 3 raters . The ICC for the total score was.56 ( 95 % confidence interval=.47-.65 ) for ratings by individuals , and the ICC for consensus ratings was.68 ( 95 % confidence interval=.57-.76 ) . DISCUSSION AND CONCLUSION The reliability of ratings of PEDro scale items varied from " fair " to " substantial , " and the reliability of the total PEDro score was " fair " to " good . Potdevin , FJ , Alberty , ME , Chevutschi , A , Pelayo , P , and Sidney , MC . Effects of a 6-week plyometric training program on performances in pubescent swimmers . J Strength Cond Res 25(X ) : 000 - 000 , 2010-This study examined in pubescent swimmers the effects on front crawl performances of a 6-week plyometric training ( PT ) in addition to the habitual swimming program . Swimmers were assigned to a control group ( n = 11 , age : 14.1 ± 0.2 years ; GCONT ) and a combined swimming and plyometric group ( n = 12 , age : 14.3 ± 0.2 years ; GSP ) , both groups swimming 5.5 h·wk−1 during a 6-week preseason training block . In the GSP , PT consisted of long , lateral high and depth jumps before swimming training 2 times per week . Pre and posttests were performed by jump tests ( squat jump [ SJ ] , countermovement jump [ CMJ ] ) and swim tests : a gliding task , 400- and 50-m front crawl with a diving start ( V400 and V50 , m·s−1 ) , and 2 tests with a water start without push-off on the wall ( 25 m in front crawl and 25 m only with kicks ) . Results showed improvement only for GSP for jump tests ( Δ = 4.67 ± 3.49 cm ; Δ = 3.24 ± 3.17 cm ; for CMJ and SJ , respectively ; p < 0.05 ) and front crawl tests ( Δ = 0.04 ± 0.04 m·s−1 ; Δ = 0.04 ± 0.05 m·s−1 ; for V50 and V400 , respectively ; p < 0.05 ) . Significant correlations were found for GSP between improvements in SJ and V50 ( R = 0.73 , p < 0.05 ) . Results suggested a positive effect of PT on specific swimming tasks such as dive or turn but not in kicking propulsion . Because of the practical setup of the PT and the relevancy of successful starts and turns in swimming performances , it is strongly suggested to incorporate PT in pubescent swimmers ' training and control it by jump performances Sunde , A , Støren , Ø , Bjerkaas , M , Larsen , MH , Hoff , J , and Helgerud , J. Maximal strength training improves cycling economy in competitive cyclists . J Strength Cond Res 24(8 ) : 2157 - 2165 , 2010-The purpose of the present study was to investigate the effect of maximal strength training on cycling economy ( CE ) at 70 % of maximal oxygen consumption ( & OV0312;o2max ) , work efficiency in cycling at 70 % & OV0312;o2max , and time to exhaustion at maximal aerobic power . Responses in 1 repetition maximum ( 1RM ) and rate of force development ( RFD ) in half-squats , & OV0312;o2max , CE , work efficiency , and time to exhaustion at maximal aerobic power were examined . Sixteen competitive road cyclists ( 12 men and 4 women ) were r and omly assigned into either an intervention or a control group . Thirteen ( 10 men and 3 women ) cyclists completed the study . The intervention group ( 7 men and 1 woman ) performed half-squats , 4 sets of 4 repetitions maximum , 3 times per week for 8 weeks , as a supplement to their normal endurance training . The control group continued their normal endurance training during the same period . The intervention manifested significant ( p < 0.05 ) improvements in 1RM ( 14.2 % ) , RFD ( 16.7 % ) , CE ( 4.8 % ) , work efficiency ( 4.7 % ) , and time to exhaustion at pre-intervention maximal aerobic power ( 17.2 % ) . No changes were found in & OV0312;o2max or body weight . The control group exhibited an improvement in work efficiency ( 1.4 % ) , but this improvement was significantly ( p < 0.05 ) smaller than that in the intervention group . No changes from pre- to postvalues in any of the other parameters were apparent in the control group . In conclusion , maximal strength training for 8 weeks improved CE and efficiency and increased time to exhaustion at maximal aerobic power among competitive road cyclists , without change in maximal oxygen uptake , cadence , or body weight . Based on the results from the present study , we advise cyclists to include maximal strength training in their training programs This study was undertaken to compare the effects of dry-l and strength training with a combined in-water resisted- and assisted-sprint program in swimmer athletes . Twenty-one swimmers from regional to national level participated in this study . They were r and omly assigned to 3 groups : the strength ( S ) group that was involved in a dry-l and strength training program where barbells were used , the resisted- and assisted-sprint ( RAS ) group that got involved in a specific water training program where elastic tubes were used to generate resistance and assistance while swimming , and the control ( C ) group which was involved in an aerobic cycling program . During 12 weeks , the athletes performed 6 training sessions per week on separate days . All of them combined the same aerobic dominant work for their basic training in swimming and running with their specific training . Athletes were evaluated 3 times : before the training program started , after 6 weeks of training , and at the end of the training program . The outcome values were the strength of the elbow flexors and extensors evaluated using an isokinetic dynamometer , and the speed , stroke rate , stroke length , and stroke depth observed during a 50-meter sprint . No changes were observed after 6 weeks of training . At the end of the training period , we observed significant increases in swimming velocity , and strength of elbow flexors and extensors both in the S and RAS groups . However , stroke depth decreased both in the S and RAS groups . Stroke rate increased in the RAS but not in the S group . However , no significant differences in the swimming performances between the S and RAS groups were observed . No significant changes occurred in C. Altogether , programs combining swimming with dry-l and strength or with in-water resisted- and assisted-sprint exercises led to a similar gain in sprint performance and are more efficient than traditional swimming training methods alone |
12,157 | 25,740,673 | There were no significant different between bicarbonate- and lactate-buffered solutions for mortality , serum bicarbonate levels , serum creatinine , serum base excess , serum pH , carbon dioxide partial pressure , central venous pressure and serum electrolytes .
Patients treated with bicarbonate-buffered solutions may experience fewer cardiovascular events , lower serum lactate levels , higher mean arterial pressure and less hypotensive events .
With the exception of mortality , we were not able to assess the main primary outcomes of this review - length of time in ICU , total length of hospital stay and relapse | BACKGROUND Acute kidney injury ( AKI ) is a severe loss of kidney function that results in patients ' inability to appropriately excrete nitrogenous wastes and creatinine .
Continuous haemodiafiltration ( HDF ) or haemofiltration ( HF ) are commonly used renal replacement therapies for people with AKI .
Buffered dialysates and solutions used in HDF or HF have varying effects on acid-base physiology and several electrolytes .
The benefits and harms of bicarbonate- versus lactate-buffered HDF or HF solutions for treating patients with AKI remain unclear .
OBJECTIVES To assess the benefits and harms of bicarbonate- versus lactate-buffered solutions for HDF or HF for treating people with AKI . | CONTEXT Although acute renal failure ( ARF ) is believed to be common in the setting of critical illness and is associated with a high risk of death , little is known about its epidemiology and outcome or how these vary in different regions of the world . OBJECTIVES To determine the period prevalence of ARF in intensive care unit ( ICU ) patients in multiple countries ; to characterize differences in etiology , illness severity , and clinical practice ; and to determine the impact of these differences on patient outcomes . DESIGN , SETTING , AND PATIENTS Prospect i ve observational study of ICU patients who either were treated with renal replacement therapy ( RRT ) or fulfilled at least 1 of the predefined criteria for ARF from September 2000 to December 2001 at 54 hospitals in 23 countries . MAIN OUTCOME MEASURES Occurrence of ARF , factors contributing to etiology , illness severity , treatment , need for renal support after hospital discharge , and hospital mortality . RESULTS Of 29 269 critically ill patients admitted during the study period , 1738 ( 5.7 % ; 95 % confidence interval [ CI ] , 5.5%-6.0 % ) had ARF during their ICU stay , including 1260 who were treated with RRT . The most common contributing factor to ARF was septic shock ( 47.5 % ; 95 % CI , 45.2%-49.5 % ) . Approximately 30 % of patients had preadmission renal dysfunction . Overall hospital mortality was 60.3 % ( 95 % CI , 58.0%-62.6 % ) . Dialysis dependence at hospital discharge was 13.8 % ( 95 % CI , 11.2%-16.3 % ) for survivors . Independent risk factors for hospital mortality included use of vasopressors ( odds ratio [ OR ] , 1.95 ; 95 % CI , 1.50 - 2.55 ; P<.001 ) , mechanical ventilation ( OR , 2.11 ; 95 % CI , 1.58 - 2.82 ; P<.001 ) , septic shock ( OR , 1.36 ; 95 % CI , 1.03 - 1.79 ; P = .03 ) , cardiogenic shock ( OR , 1.41 ; 95 % CI , 1.05 - 1.90 ; P = .02 ) , and hepatorenal syndrome ( OR , 1.87 ; 95 % CI , 1.07 - 3.28 ; P = .03 ) . CONCLUSION In this multinational study , the period prevalence of ARF requiring RRT in the ICU was between 5 % and 6 % and was associated with a high hospital mortality rate Objective To evaluate the effect of high-volume hemofiltration ( HVHF ) with lactate-buffered replacement fluids on acid-base balance . Design R and omized crossover study . Setting Intensive Care Unit of Tertiary Medical Center Participants Ten patients with septic shock and acute renal failure . Interventions R and om allocation to 8 h of isovolemic high-volume hemofiltration ( ultrafiltration rate : 6 l/h ) or 8 h of isovolemic continuous venovenous hemofiltration ( ultrafiltration rate : 1 l/h ) with lactate-buffered replacement fluid with subsequent crossover . Measurements and results We measured blood gases , electrolytes , albumin , and lactate concentrations and completed quantitative biophysical analysis of acid-base balance changes . Before high-volume hemofiltration , patients had a slight metabolic alkalosis [ pH : 7.42 ; base excess ( BE ) 2.4 mEq/l ] despite hyperlactatemia ( lactate : 2.51 mmol/l ) . After 2 h of high-volume hemofiltration , the mean lactate concentration increased to 7.30 mmol/l ( p=0.0001 ) . However , a decrease in chloride , strong ion difference effective , and strong ion gap ( SIG ) compensated for the effect of iatrogenic hyperlactatemia so that the pH only decreased to 7.39 ( p=0.05 ) and the BE to −0.15 ( p=0.001 ) . After 6 h , despite persistent hyperlactatemia ( 7 mmol/l ) , the pH had returned to 7.42 and the BE to 2.45 mEq/l . These changes remained essentially stable at 8 h. Similar but less intense changes occurred during continuous venovenous hemofiltration . Conclusions HVHF with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia . However , such hyperlactatemia only has a mild and transient acidifying effect . A decrease in chloride and strong ion difference effective and the removal of unmeasured anions all rapidly compensate for this effect BACKGROUND Acute renal failure is a serious complication in critically ill patients and frequently requires renal replacement therapy , which alters trace element and vitamin metabolism . OBJECTIVE The objective was to study trace element balances during continuous renal replacement therapy ( CRRT ) in intensive care patients . DESIGN In a prospect i ve r and omized crossover trial , patients with acute renal failure received CRRT with either sodium bicarbonate ( Bic ) or sodium lactate ( Lac ) as a buffering agent over 2 consecutive 24-h periods . Copper , selenium , zinc , and thiamine were measured with highly sensitive analytic methods in plasma , replacement solutions , and effluent during 8-h periods . Balances were calculated as the difference between fluids administered and effluent losses and were compared with the recommended intakes ( RI ) from parenteral nutrition . RESULTS Nineteen sessions were conducted in 11 patients aged 65 + /- 10 y. Baseline plasma concentrations of copper were normal , whereas those of selenium and zinc were below reference ranges ; glutathione peroxidase was in the lower range of normal . The replacement solutions contained no detectable copper , 0.01 micromol Se/L ( Bic and Lac ) , and 1.42 ( Bic ) and 0.85 ( Lac ) micromol Zn/L. Micronutrients were detectable in all effluents , and losses were stable in each patient ; no significant differences were found between the Bic and Lac groups . The 24-h balances were negative for selenium ( -0.97 micromol , or 2 times the daily RI ) , copper ( -6.54 micromol , or 0.3 times the daily RI ) , and thiamine ( -4.12 mg , or 1.5 times the RI ) and modestly positive for zinc ( 20.7 micromol , or 0.2 times the RI ) . CONCLUSIONS CRRT results in significant losses and negative balances of selenium , copper , and thiamine , which contribute to low plasma concentrations . Prolonged CRRT is likely to result in selenium and thiamine depletion despite supplementation at recommended amounts UNLABELLED Clinical experience with two physiologic bicarbonate/lactate peritoneal dialysis solutions in automated peritoneal dialysis . BACKGROUND Patients on automated peritoneal dialysis ( APD ) usually receive larger volumes of dialysis solution and more frequent , shorter exchanges than patients on continuous ambulatory peritoneal dialysis ( CAPD ) , and therefore are likely to derive greater benefit from more physiologic solutions . METHODS Peritoneal dialysis solutions containing 25 mmol/L bicarbonate and either 10 or 15 mmol/L lactate were compared with st and ard lactate solutions ( 35 or 40 mmol/L ) in two prospect i ve , open-label studies of patients on APD . Each study included a 2-week baseline period ( lactate solution ) , a 6-week treatment period ( bicarbonate/lactate solution ) , and a 2-week follow-up period ( same lactate solution as baseline ) . Biochemical analyses and assessment s of vital signs and safety parameters were conducted at baseline , every 2 weeks during treatment , and at the end of the follow-up period . A product use question naire was administered in one study at the end of treatment . RESULTS A statistically significant rise in plasma bicarbonate ( approximately 2 mmol/L ) occurred when patients switched from a lactate solution to the bicarbonate/lactate solution with equimolar buffer concentration ( P < 0.001 for each solution ) . Plasma bicarbonate decreased by 1.16 mmol/L after a switch from lactate 40 mmol/L to bicarbonate/lactate 35 mmol/L ( P < 0.001 ) . When patients switched to bicarbonate/lactate 35 , the majority of individual venous plasma bicarbonate values were in the normal range . A switch from a lower calcium ( 1.25 mmol/ L ) lactate solution to a higher calcium ( 1.75 mmol/L ) lactate/bicarbonate solution result ed in a statistically significant rise in serum calcium ( 0.06 mmol/L , P < 0.018 ) . The product use question naire revealed improvements in symptoms , including reduced pain on infusion . CONCLUSION Bicarbonate/lactate solutions may be used safely and effectively in patients on APD . The availability of 2 formulations with different buffer and calcium content provides flexibility for the control of acidosis as well as calcium balance Objective We evaluated the variable Kt/V , which has become established in the therapy of end-stage renal disease in acute renal failure , to assess the influence of the filtration volume of continuous venovenous hemofiltration on Kt/V. We measured the variables of acid-base balance and uremia control . Design Prospect i ve interventional pilot study . Setting Medical intensive care unit of a university hospital . Patients Fifty-six patients with acute renal failure and continuous venovenous hemofiltration treatment . Interventions The patients were consecutively treated with a filtration volume of either 1 L/hr ( group 1 ) or 1.5 L/hr ( group 2 ) . Measurements and Main Results Patients with a filtration volume of 1.5 L/hr achieved a Kt/V of 0.8 per day , which was significantly higher than in the patient group treated with 1 L/hr ( 0.53 , p < .05 ) . The filtration volume of 1.5 L/hr led to a markedly better control of blood urea nitrogen concentrations , 69.3 ± 6.6 mg/dL vs. 52.1 ± 5.2 ( p < .05 ) , and to a much quicker and longer lasting compensation of acidosis . Both groups had acidotic pH at the beginning of therapy ( group 1 , 7.29 ± 0.02 ; group 2 , 7.29 ± 0.02 , nonsignificant ) . In group 2 , a significantly higher pH value than in group 1 was measured after 24 hrs of continuous venovenous hemofiltration ( p < .001 ; 7.39 ± 0.02 vs. 7.31 ± 0.02 ) . The pH values in group 1 did not normalize until after 4 days . The filtration volume of 1.5 L/hr led to a quicker increase in bicarbonate concentrations after 24 hrs of therapy ( group 1 , 2.8 ± 3.2 mmol/L ; group 2 , 6.5 ± 3.1 mmol/L , p < .001 ) . Conclusions The st and ardized urea clearance Kt/V is a valuable tool in the treatment of acute renal failure . Higher Kt/V levels were associated with a better control of uremia and acid-base balance . However , there were no differences in the clinical course , patient survival , percentage of patients with or without renal failure who were transferred from the intensive care unit , or Acute Physiology and Chronic Health Evaluation III scores The characteristics of acetate-free biofiltration ( AFB ) are now well documented in patients with chronic renal failure : hemodynamic tolerance , correction of acid-base imbalance , buffer-free dialysate ( without acetate ) and absence of backfiltration . This hemodialysis technique can be beneficial to patients with acute renal failure ( ARF ) . In our intensive care unit , we prospect ively studied 29 patients with isolated ARF or ARF associated with failure of other organs . All eligible patients were r and omly assigned to undergo dialysis with bicarbonate hemodialysis ( BH ) or with ( AFB ) . All used the same high flux biocompatible dialysis membranes . Effectiveness and hemodynamic tolerance of hemodialysis sessions and evolution of patients were analyzed . Correction of metabolic disorders , although better in the AFB group was not statistically different from that in the BH group . Re-equilibration of acid-base balance was also similar , with or without mechanical ventilation . Heparin consumption was significantly higher in the AFB group , with no effect on haemorrhagic complications . Analysis of hypo- and hypertensive episodes , defined as arterial pressure ( AP ) variations 20 % greater than initial pressure , showed no difference in terms of number or degree of AP variation . However , weight loss and the rate of ultrafiltration led to a higher hypotensive risk in the BH group ( p < 0.05 ) . Finally , the clinical course and prognosis was similar in both groups . In summary , AFB may be considered as effective a hemodialysis technique as BH in patients with ARF . Weight loss was better tolerated in the AFB group and can be a favorable factor considering the deleterious effect of overhydration in patients admitted to an intensive care unit . This study invites a comparison of longer dialysis session of AFB therapy and continuous hemodiafiltration Objective To compare the hemodynamic response of ICU patients with acute renal failure of a 24-h continuous arteriovenous hemofiltration ( CAVH ) and that of patients with a 4-h intermittent hemodialysis ( HD ) . Design Cross-over r and omized clinical trial . The two periods to be compared were a 24-h CAVH and the 24-h encompassing a 4-h HD . These two periods were separated by a 24-h wash-out period . Setting Ten bed medicosurgical ICU of a tertiary care center in Paris , France . Patients Inclusion criterion was the requirement of replacement therapy for acute renal failure in patients already su bmi tted to mechanical ventilation . Interventions CAVH was performed with Ringers ' lactate used for restitution and infused before the hemofilter . The ultrafiltrate output was maintained at around 15 ml/min . HD was performed with a bicarbonate-buffered dialysate . Mean outcome measures Mean arterial pressure ( MAP ) , use of adrenergic drugs , and change in body weight during each period . Results Twenty-seven consecutive patients were included , 15 CAVH-HD and 12HD-CAVH . CAVH and HD allowed the same metabolic efficacy . No hemodynamic parameter ( MAP , amount of adrenergic drugs , change in body weight ) differed between the two methods . Conclusions CAVH is equivalent to HD in terms of MAP and the use of vasopressive drugs and fluids . Establishing the superiority of CAVH would require carefully controlled studies assessing either outcome or changes in tissue oxygenation There are very limited data on overall epidemiology of ARF . It is crucial to know the incidence , etiology and clinical feature of ARF to promote prevention strategies and to implement adequate re sources for the management of this entity . During a nine month period , a collaborative prospect i ve protocol with 98 variables was developed to assess all ARF episodes encountered in the 13 tertiary-care hospitals in Madrid , Spain ( covering 4.2 million people of over 14 years of age ) . ARF was considered when a sudden rise in serum creatinine concentration ( SCr ) to more than 177 mumol/liter was found in patients with normal renal function , or when the sudden rise ( 50 % or more ) was observed in patients with previous mild-to-moderate chronic renal failure ( SCr < 264 mumol/liter ) . Of the 748 cases of ARF studied , 665 episodes presented in inhabitants from the Madrid area . This gives an overall incidence of ARF of 209 cases per million population ( p.m.p . ; 95 % CJ 195 to 223 ) . The incidence of acute tubular necrosis ( ATN ) was 88 cases p.m.p . ( 95 % CI 79 to 97 ) , prerenal ARF 46 p.m.p ( 95 % CI 40 to 52 ) , acute-onset chronic ARF 29 p.m.p . ( 95 % CI 24 to 34 ) , and obstructive ARF 23 p.m.p . ( 95 % CI 19 to 27 ) . The mean age was 63 + /- 17 years . The most frequent causes of ARF were ATN ( 45 % ) , prerenal ( 21 % ) , acute-onset chronic renal failure ( 12.7 % ) and obstructive ARF ( 10 % ) . Renal function was normal at admission in 48 % of patients who later developed ARF . Mortality ( 45 % ) was much higher than that of the other patients admitted ( 5.4 % , P < 0.001 ) . This real outcome correlated extremely well with the expected outcome calculated through out the severity index of ARF ( SI ) 0.433 + /- 0.246 ( mean + /- SD ) . In 187 cases , mortality was attributed to underlying disease , thus corrected mortality due to ARF was 26.7 % . Dialysis was required in 36 % of patients , and was associated with a significantly higher SI of ARF ( 0.57 + /- 0.23 vs. 0.35 + /- 0.19 , P < 0.001 ) and mortality ( 65.9 vs. 33.2 % , P < 0.001 ) . Mortality in patients hemodialyzed with biocompatible synthetic membranes ( N = 50 ) was similar to that observed with cellulosic ones ( N = 84 ; 66 % vs. 59.5 % , NS ) . Mortality was higher in patients with coma , assisted respiration , hypotension , jaundice ( all P < 0.001 ) and oliguria ( P < 0.02 ) . This study gives , for the first time , the incidence of all forms of ARF in a developed country . ARF is iatrogenically induced at a high rate by modern medicine . Prevention strategies , particularly in the perioperative period , are needed to decrease its impact Objective To evaluate , quantify and compare the effects of continuous veno-venous hemofiltration ( CVVH ) with lactate or bicarbonate-buffered replacement fluids on acid-base balance . Design R and omized double crossover study . Setting Intensive Care Unit of Tertiary Medical Center . Participants Eight patients with severe acute renal failure . Interventions R and om allocation to either 2 hours of isovolemic lactate-buffered ( treatment A ) CVVH or 2 hours of bicarbonate-buffered ( treatment B ) CVVH with cross over and with same procedure repeated the following day ( double cross over ) . Measurements and Results Timed collection s of arterial blood and ultrafiltrate ( UF ) , measurement of blood and UF gases and lactate concentrations and calculation of buffer-base mass balance . At baseline , both groups of patients had a similar , slight metabolic alkalosis ( pH : 7.45 vs. 7.45 ; BE 3.9 mEq/L for treatment A and 4.0 for treatment B ) and a serum bicarbonate of 28.1 mmol/L for treatment A vs. 28.3 mmol/L for treatment B ; all NS . This alkalosis was present despite slight hyperlactatemia in both groups ( A : 2.4 mmol/L vs. B 2.8 mmol/L ; NS ) . Within 60 minutes of treatment , however , treatment A led to a significantly higher lactate concentration ( 3.9 vs 2.5 mmol/L ; p=0.0011 ) , a significantly lower BE ( 2.3 vs 4.1 mEq/L ; p=0.0019 ) and a significantly lower bicarbonate concentration ( 26.7 vs. 28.3 mmol/L ; p=0.0038 ) in the presence of an unchanged PaCO2 . These differences persisted during the study period . The UF of patients receiving treatment A contained more lactate ( 10.2 vs 2.9 mmol/L ; p<0.0001 ) and less bicarbonate ( 25.6 vs. 30.8 mmol/L ; p<0.0001 ) than treatment B result ing in a mean buffer-base balance of + 20.4 mEq/h compared to −2.6 mEq/h for treatment B ; p<0.0001 ) . Conclusions CVVH with lactate-buffered replacement fluids induces iatrogenic hyperlactatemia . Such hyperlactatemia is associated with an acidifying effect despite a positive buffer-base balance Background and aims Continuous veno – venous haemofiltration ( CVVH ) is an established treatment for acute renal failure ( ARF ) . Recently , extended intermittent dialytic techniques have been proposed for the treatment of ARF . The aim of this study was to compare these two approaches . Setting Intensive care unit of tertiary hospital . SubjectsSixteen critically ill patients with ARF . Design R and omised controlled trial . InterventionWe r and omised sixteen patients to three consecutive days of treatment with either CVVH ( 8) or extended daily dialysis with filtration ( EDDf ) ( 8) and compared small-solute , electrolyte and acid – base control . Results There was no significant difference between the two therapies for urea or creatinine levels over 3 days . Of 80 electrolyte measurements taken before treatment , 19 were abnormal . All values were corrected as a result of treatment , except for one patient in the CVVH group who developed hypophosphataemia ( 0.54 mmol/l ) at 72 h. After 3 days of treatment , there was a mild but persistent metabolic acidosis in the EDDf group compared to the CVVH group ( median bicarbonate : 20 mmol/l vs. 29 mmol/l : p = 0.039 ; median base deficit : –4 mEq/l vs. –2.1 mEq/l , p = 0.033 ) . Conclusions CVVH and EDDf as prescribed achieved similar control of urea , creatinine and electrolytes . Acidosis was better controlled with CVVH PURPOSE The purpose of this review is to characterize the nephrotoxicity noted in newly diagnosed patients under 21 years of age after treatment with ifosfamide-containing chemotherapy regimens and local irradiation for localized gross residual rhabdomyosarcoma or undifferentiated sarcoma . PATIENTS AND METHODS From 1987 to 1991 , 194 previously untreated patients received vincristine and ifosfamide plus dactinomycin or etoposide for 1 - 2 years . Ifosfamide was given at 1.8 g/m2/day for 5 days with sodium mercaptoethane sulfonate , or 9 g/m2 of ifosfamide per course . The three-drug regimen was repeated every 3 - 4 weeks . RESULTS Twenty-eight patients ( 14 % ) developed renal toxicity : 19 had renal tubular dysfunction ( RTD ) characterized by low serum phosphate ( < or = 3 mg/dl ) or bicarbonate ( < 20 or = mEq/L ) levels , five had decreased glomerular function ( DGF ) , and four had both RTD and DGF . When nine or more courses of ifosfamide ( > 72 g/m2 ) were given , children < 3 years of age had a higher incidence of RTD than did children > or = 3 years of age ( 34 % versus 6 % ; p < 0.001 ) . A similar age difference was observed even when eight or fewer courses ( < or = 72 g/m2 ) were given ( p = 0.03 ) . A matched case-control comparison showed that renal abnormalities at diagnosis , chiefly hydronephrosis , also increased the risk of renal tubular injury by ifosfamide by a factor of 13 ( p < 0.001 ) . Patients with DGF tended to be older than those with RTD , and all but one received > 72 g/m2 of ifosfamide . CONCLUSIONS Patients who are < 3 years of age who receive more than eight courses ( > 72 g/m2 ) of ifosfamide and who have a preexisting renal abnormality have an increased risk of RTD and DGF . The renal function of patients being considered for ifosfamide treatment must be carefully monitored . Ifosfamide should be avoided in patients with renal abnormalities at diagnosis unless the potential benefit clearly exceeds the risk of further renal impairment Objective : To compare the effect of lactate vs. bicarbonate‐buffered replacement fluids on electrolyte mass balance during isovolemic continuous veno‐venous hemofiltration ( CVVH ) . Design : R and omized controlled study with double cross over . Setting : Intensive care unit of a tertiary university hospital . Patients and participants : Eight patients with acute renal failure ( ARF ) . Interventions : Isovolemic CVVH ( 2L/hr of replacement fluid ) was performed in r and om order with either bicarbonate or lactate‐buffered replacement fluid delivered pre‐filter . Measurements and Results : Sodium , potassium , chloride , magnesium , and phosphate , were measured in each sample . There was a mass gain of sodium , which was similar under both conditions ( bicarbonate : 23.3 ± 4.9 mmol/hr , lactate : 22.7 ± 3.5 mmol/hr ) . Mass chloride gains occurred with bicarbonate‐buffered replacement fluid only ( 12.8 ± 5.3 mmol/hr ) , while there was an overall net loss of chloride with lactate fluids ( − 2.5 ± 5.2 mmol/hr ) , result ing in a significant difference in chloride mass balance ( p < 0.0001 ) . Magnesium mass balance was negative with bicarbonate buffer only ( − 0.6 ± 0.2 mmol/hr ) and also differed significantly from that obtained with lactate fluids ( − 0.1 ± 0.2 mmol/hr , p < 0.0001 ) . Phosphate losses ( bicarbonate : − 1.7 ± 0.7 mmol/hr , lactate : − 1.7 ± 0.5 mmol/hr ) were equivalent with both buffers . Potassium mass balance was neutral . Conclusions : Mass balance during isovolemic CVVH is significantly affected by the type of replacement fluid administered pre‐filter . Isovolemic CVVH is not isonatremic and the use of bicarbonate‐buffered fluid results in a significant accumulation of chloride and a loss of magnesium The efficacy of vigorous dialysis in the management of acute renal failure remains controversial . In order to examine the beneficial role of vigorous dialysis , a prospect i ve study was carried out in 34 patients paired by acute renal failure etiology and treated with sufficient dialysis to maintain predialysis blood urea nitrogen and serum creatinine below either 60 and 5 mg/dl ( intensive ) or 100 and 9 mg/dl , respectively ( non-intensive ) . Serum creatinine was at least 8 mg/dl in all patients prior to r and om assignment to intensive or non-intensive dialysis . Mean predialysis blood urea nitrogen and serum creatinine , respectively , were 60 + /- 23 and 5.3 + /- 1.5 mg/dl in the intensively dialyzed group and 101 + /- 18 and 9.1 + /- 1.4 mg/dl in the non-intensively dialyzed group ( both p less than .001 ) . Predialysis serum bicarbonate and blood pH were lower and serum phosphate higher in the non-intensively dialyzed patients . Daily weight changes , increases in blood urea nitrogen , protein and calorie intakes were similar . While hemorrhagic episodes tended to be more frequent in non-intensively dialyzed patients , overall complication rates were not different between the two groups . Mortality rates , which were 58.8 % in the intensive and 47.1 % in the non-intensive groups , also were not different . On the other h and , urine output prior to dialysis did influence survival . It is concluded that , within the limits of the study , there is no advantage to intensive dialysis in the management of acute renal failure Objective : To determine the impact of different hemofiltration ( HF ) replacement fluids on the acid-base status and cardiovascular hemodynamics in patients with acute renal failure ( ARF ) and continuous veno-venous hemofiltration (CVVH).¶ Design : Prospect i ve , cohort study .¶ Setting : Intensive Care Unit of the Heinrich Heine University Hospital , Düsseldorf , Germany.¶Subject and methods : One hundred and thirty-two critically ill patients with acute renal failure and continuous veno-venous HF were studied . Fifty-two patients were subjected to lactate-based ( group 1 ) , and 32 to acetate-based hemofiltration ( group 2)while 48 ( group 3 ) were treated with bicarbonate-based buffer hemofiltration fluid . Fifty-seven had a septic , and 75 a cardiovascular , origin of the ARF . Creatinine , blood urea nitrogen ( BUN ) , serum bicarbonate , arterial pH , lactate and Apache II scores were noted daily.¶Main results : The mean CVVH duration was 9.8 ± 8.1 days , mortality was 65 % . No difference was present between the groups under investigation with regard to the main clinical parameters . Lactate- and bicarbonate-based hemofiltration led to significantly higher serum bicarbonate and arterial pH values as compared to the acetate-based hemofiltration . Serum bicarbonate values at 48 h after the initiation of CVVH treatment were 25.7 ± 3.8 mmol/l ( p < 0.001 ) in group 1 , 20.6 ± 3.1 mmol/l in group 2 and 23.3 ± 3.9 mmol/l ( p < 0.001 ) in group 3 . While a lack of increase in serum bicarbonate and arterial pH was correlated to poor prognosis in lactate- and bicarbonate-based hemofiltration , no such observation was made in acetate-based hemofiltration . Cardiovascular hemodynamics were superior in patients treated with lactate- and bicarbonate-based buffer solution as compared to those treated with acetate-based buffer solution.¶ Conclusions : The degree of correction of acidosis during hemofiltration was determined by patient outcome in patients treated with lactate- and bicarbonate-based buffer solutions , but not in patients receiving acetate-buffered solution . Bicarbonate and lactate-based buffer solutions were found to be superior to acetate-based replacement fluid Abstract . Objective : To evaluate whether high volume haemofiltration improves haemodynamics and affects serum cytokine and complement concentrations in human septic shock . Design and setting : R and omized cross-over clinical trial in a tertiary intensive care unit . Patients : Eleven patients with septic shock and multi-organ failure . Interventions : Patients were assigned to either 8 h of high-volume haemofiltration ( HVHF ; 6 l/h ) or 8 h of st and ard continuous veno-venous haemofiltration ( CVVH ; 1 l/h ) in r and om order . Measurements and main results : We measured changes in haemodynamic variables , dose of norepinephrine required to maintain a mean arterial pressure greater than 70 mmHg and plasma concentrations of complement anaphylatoxins and several cytokines . An 8-h period of HVHF was associated with a greater reduction in norepinephrine requirements than a similar period of CVVH ( median reduction : 10.5 vs. 1.0 µg/min ; p=0.01 ; median percentage reduction : 68 vs. 7 % ; p=0.02 ) . Both therapies were associated with a temporary reduction ( p<0.01 ) in the plasma concentration of C3a , C5a , and interleukin 10 within 2 h of initiation . HVHF was associated with a greater reduction in the area under the curve for C3a and C5a ( p<0.01 ) . The concentration of the measured soluble mediators in the ultrafiltrate was negligible . Conclusions : HVHF decreases vasopressor requirements in human septic shock and affects anaphylatoxin levels differently than st and ard Aims To assess the safety and efficacy of two different commercial citrate containing pre-filter replacement fluids during continuous veno-venous hemofiltration ( CVVH ) in patients with frequent filter clotting . Setting : Four intensive care units . Patients : Sixty-three critically ill patients with acute renal failure ( ARF ) . Design : Prospect i ve observational study . Methods We used a commercial citrate fluid ( citrate : 11 mmol/L - fluid A ) as predilution replacement for CVVH . We then changed to a new commercial citrate fluid ( citrate : 14 mmol/L-fluid B ) as replacement fluid and performed statistical comparisons . Replacement fluid rate was fixed at 2,000 ml/hour . Results Filter life was 12.2 hour with fluid A compared with 17.1 hour with fluid B on average ( p=0.0001 ) . Mean post filter ionized calcium concentration was 0.52 mmol/L with fluid A compared with 0.40 mmol/L with fluid B ( P&0.0001 ) . Citrate intolerance led to cessation of treatment in one patient with fluid A and one patient with fluid B. Overall ionized calcium levels were higher ( A : 1.18 vs B : 1.13 mmol/L ; P&0.0001 ) and bicarbonate was lower ( A : 22.4 vs B : 24.5 mmol/L ; P&0.0001 ) during treatment with fluid A. Alkalemia was seen in 10 patients treated with fluid A and 16 patients treated with fluid B ( NS ) . Conclusions We have developed a simple approach to regional citrate anticoagulation for CVVH using a commercial citrate-containing fluid as replacement fluid . Increasing citrate concentration from 11 to 14 mmol/L increased filter life while maintaining relative safety and simplicity Acute renal failure usually occurs during hospitalization , but may also be present on admission to the hospital . To define the causes and outcomes of community-acquired acute renal failure , we undertook a prospect i ve study of patients admitted to the hospital with acute elevations in serum creatinine concentrations . Over a 17-month period , all admission serum creatinine determinations were screened for patients with values greater than 177 mumol/L ( 2 mg/dL ) . These values were compared with baseline creatinines to select patients with an acute elevation in serum creatinine occurring outside the hospital . One hundred patients were entered into the study , with an overall incidence of 1 % of hospital admissions . Seventy percent of the patients had prerenal azotemia , 11 % had intrinsic acute renal failure , 17 % had obstruction , and 2 % could not be classified . Mean peak serum creatinine ( 318 + /- 18 mumol/L [ 3.6 + /- 0.2 mg/dL ] ) and mortality ( 7 % ) was lowest in the group with prerenal azotemia . In this group , volume contraction due to vomiting , decreased fluid intake , diarrhea , fever , glucosuria , or diuretics was the most common underlying cause . The group with intrinsic acute renal failure had the most severe renal failure and the highest mortality ( 55 % ) . Although ischemic acute tubular necrosis is the most common cause of hospital-acquired intrinsic acute renal failure , this etiology was seen in only one patient . Drug-induced nephrotoxicity and infection-related causes were the most common underlying etiologies of intrinsic acute renal failure . Obstructive renal failure had a mortality of 24 % and was most commonly due to benign prostatic hypertrophy . ( ABSTRACT TRUNCATED AT 250 WORDS Haemodialysis ( HD ) and peritoneal dialysis ( PD ) remains the cornerstone of management of patients with renal failure in developing countries as renal transplantation is just developing in most . Although both HD and PD are cost intensive , specific advantages and disadvantages have been identified with either of them . Comparative assessment of their effectiveness , benefits and cost will assist in providing a rational basis for preference of one or the other especially in third world countries where renal replacement therapy remains unaffordable and therefore relatively inaccessible to majority of patients . We therefore conducted this prospect i ve r and omised study to compare the effectiveness , benefits , cost and complications of acute or intermittent PD ( IPD ) and HD using locally manufactured PD fluids . Two groups of twenty patients with renal failure matched for age and clinical diagnosis were managed with IPD and HD and the effectiveness , costs and complications of both modalities compared . We found that both were comparably effective in the control of uraemia with significant reductions in the serum urea , creatinine and potassium from 29.2 + /- 7.2 mmol/L , 1693.7 + /- 580.5micromol/L and 4.8 + /- 1.2 mmol/L to 13.2 + /- 4.6 mmol/L , 796.0 + /- 458.0micromol/ L and 3.3 + /- 0.6 mmol/L respectively for IPD ( P<0.05 ) and 34.4 + /- 9.0mmol/L , 1536.0 + /- 832.5 micromol/L and 4.8 + /- 1.3 mmoV L to 14.6 + /- 7.5 mmol/L , 830.0 + /- 570.7 micromol/L and 3.9 + /- 0.8 mmol/L respectively for HD ( P<0.05 ) . In addition , there were significant improvements in serum bicarbonate in both groups . There was no significant difference in percentage reduction in serum urea , creatinine and serum potassium in both groups ( P>0.05 ) . However , HD managed patients required more blood transfusion ( P<0.05 ) . There were also comparably significant reductiohs in systolic , diastolic and mean arterial blood pressures in both groups ( P<0.05 ) . The costs of dialysis as well as the total cost of hospitalization were found to be significantly lower in patients managed with IPD ( P<0.05 ) . The commonest complication observed in patients managed with IPD was peritonitis while in patients managed with HD it was dialysis-induced hypotension . The clinical outcome was equally good in all the ARF patients as all of them recovered irrespective of the treatment modality ; CRF patients did not fare as well with 37.5 % mortality observed . We conclude that IPD and HD are effective renal replacement therapies with the former being significantly cheaper . IPD should be encouraged in our patients with ARF or acute exacerbation of chronic renal failure OBJECTIVE To compare acid-base balance , lactate concentration and haemodynamic parameters during continuous veno-venous haemodialysis ( CVVHD ) using bicarbonate or a lactate buffered dialysate . METHODS DESIGN prospect i ve r and omized cross-over design ; SETTING Multicentre combined adult surgical and medical intensive care units . Patients ; 26 critically ill patients starting CVVHD for acute renal failure . INTERVENTIONS Each patient to receive 48 h of bicarbonate dialysate and 48 h of lactate dialysate with the order of the 48 h block r and omized at trial entry . RESULTS The serum bicarbonate increased from baseline in both the lactate and bicarbonate groups over the first 48 h of treatment ( 16.3+/-1.53 to 22.2+/-1.41 mmol/l and 18.9+/-2.02 to 22.2+/-1.18 mmol/l , respectively ) and continued to rise towards normal over the next 48 h after cross-over to the other dialysate . The H+ and pCO2 only trended higher in the lactate group . Unlike the acid base parameters , serum lactate levels varied depending on the dialysate composition . The patients initially r and omized to the lactate dialysate had higher serum lactate levels and these tended to increase further after 48 h of dialysis from 2.4+/-0.8 to 2.6+/-0.4 mmol/l . However , in the following 48 h the lactate levels fell to 1.8+/-0.6 ( P = 0.039 ) while patients were being treated with the bicarbonate dialysate . Similar results were seen in the patients initially r and omized to the bicarbonate dialysate . Serum lactate remained stable over the first 48h ( 1.4+/-0.2 to 1.5+/-0.1 mmol/l ) but after cross-over to the lactate dialysate increased to 3.1+/-0.7 mmol/l ( P = 0.051 ) . Overall , lactate levels were significantly higher during dialysis with lactate buffered solution than bicarbonate buffered solution ( 2.92+/-0.45 vs. 1.61+/-0.25 mmol/l P = 0.01 ) . Mean arterial pressure trended higher during bicarbonate dialysis but did not reach statistical significance ( lactate vs. bicarbonate ; 71.1+/-3.1 vs. 81.3+/-5.8 mm Hg ) . Subgroup analysis of the patients with abnormal liver indices or increased lactate levels at initiation of dialysis ( n = 15 ) revealed only a trend toward better bicarbonate control ( lactate vs. bicarbonate ; 22.00+/-1.73 vs. 22.86+/-1.09 , P = 0.2 ) . However , in this group with hepatic insufficiency elevations in serum lactate were even greater during lactate compared to the bicarbonate dialysis ( 3.39+/-0.68 vs. 1.78+/-0.42 P = 0.036 ) . Patients who had elevations of lactate during lactate dialysis had a high mortality ( 6 of 7 ) . These patients had an even greater disparity in lactate levels ( 4.3+/-1.4 vs. 1.3 + /-0.3 ) and blood pressure ( 68.0+/- 7.7 vs. 87.2+/-17.1 ) between lactate and bicarbonate dialysis . Due to small patient numbers these comparisons did not achieve statistical significance . CONCLUSION During continuous veno venous haemodialysis a bicarbonate buffered dialysis solution provided equal acid-base control but maintained more normal lactate levels than a lactate buffered dialysis solution BACKGROUND Although cytokines play a pivotal role in the inflammatory responses that mediate the severity of acute renal failure ( ARF ) , the importance of pro- and anti-inflammatory cytokine gene promoter polymorphisms has been unexplored . METHODS We prospect ively evaluated the relationship of single nucleotide polymorphism in the promoter region of tumor necrosis factor alpha ( TNF-alpha ) and interleukin-10 ( IL-10 ) to mortality in 61 patients with ARF requiring intermittent hemodialysis . Cytokine genotyping was performed on leukocytes using PCR techniques . Cox proportional-hazards regression analysis was used to explore these relationships . RESULTS The mean ( + /-SD ) APACHE II score was 24 + /- 7 , MOF score 2 + /- 1 , and 64 % had sepsis . The TNF-alpha high producer genotype ( -308 A-allele carrier ) was associated with a higher risk of death after adjustment for the APACHE II score ( HR=2.5 ; P=0.04 ) , and the IL-10 intermediate/high producer genotype ( -1082 G-allele carrier ) was associated with a lower risk of death after adjustment for the MOF score ( HR=0.36 ; P=0.03 ) . Considering combinations of genotypes , the TNF-alpha high and IL-10 low producer genotype combination was associated with a approximately 6-fold increased risk of death compared to the TNF-alpha-low and IL-10 intermediate/high producer genotype combination , after adjustment for either APACHE II ( P=0.004 ) , MOF score ( P=0.004 ) or sepsis ( P=0.006 ) . CONCLUSIONS TNF-alpha and IL-10 gene polymorphisms are related to the risk of death among patients with ARF who require dialysis . Larger studies are needed to confirm these relationships Bicarbonate dialysate is cl aim ed to be superior to acetate for both chronic and acute hemodialysis . We compared acetate and bicarbonate dialysates in 30 acute renal failure patients during 120 dialyses . 4 patients were diabetic and 2 had liver failure . Patients were dialyzed alternating acetate and bicarbonate dialysate in a double-blind cross-over manner ; each patient was his own control . BUN , creatinine , Na+ , K+ , osmolality , delta osmolality , % ultrafiltration , arterial blood gases , pre , post and lowest dialysis mean arterial blood pressure , dialysis with hypotensive episodes and symptoms of hypotension were recorded . The measurements obtained for each patient during dialyses with acetate and bicarbonate were compared . There was no difference in predialysis chemistries , osmolality or osmolality fall , no change in mean arterial blood pressure or hypotensive episodes and symptoms and ultrafiltration . PCO2 and pH were slightly lower for the acetate group at the 2nd h but not at the end of dialysis . 4 patients had serum acetate determinations , all metabolized acetate normally . These findings contradict recent suggestions that severely ill patients should not be dialyzed against acetate . Since acetate is technically much easier to use and has no clinical drawbacks , it does not need to be replaced with bicarbonate in acute patients . Other factors must be more important than acetate in generating hypotension during acute dialysis BACKGROUND Bicarbonate-buffered replacement fluid ( RF-bic ) in continuous venovenous hemofiltration ( CVVH ) may be superior to lactate-buffered replacement fluid ( RF-lac ) in acute renal failure . In an open , r and omized , multicenter study , we investigated the effects of RF-bic and RF-lac on cardiovascular outcome in patients requiring CVVH following acute renal failure . METHODS One hundred seventeen patients between the age of 18 and 80 years were r and omized to CVVH either with RF-bic ( N = 61 ) or RF-lac ( N = 56 ) . Patients were treated with CVVH for five days or until either renal function was restored or the patient was removed from the study . Data were analyzed on day 5 or according to the " last observation carried forward " ( LOCF ) option . Adverse events were classified according to the WHO-Adverse Reaction Terminology system . RESULTS Blood lactate levels were significantly lower and blood bicarbonate levels were significantly higher in patients treated with RF-bic than in those treated with RF-lac ( lactate , 17.4 + /- 8.5 vs. 28.7 + /- 10.4 mg/dL , P < 0.05 ; bicarbonate , 23.7 + /- 0.4 vs. 21.8 + /- 0.5 mmol/L , P < 0 . 01 ) . The number of hypotensive crises was lower in RF-bic-treated patients than in RF-lac-treated patients ( RF-bic 14 out of 61 patients , RF-lac in 29 out of 56 patients ; 0.26 + /- 0.09 vs. 0.60 + /- 0.31 episodes per 24 h , P < 0.05 ) . Nine out of 61 patients ( 15 % ) treated with RF-bic and 21 out of 56 patients ( 38 % ) treated with RF-lac developed cardiovascular events during CVVH therapy ( P < 0 . 01 ) . A multiple regression analysis showed that the occurrence of cardiovascular events was dependent on replacement fluid and previous cardiovascular disease and not on age or blood pressure . Patients with cardiac failure died less frequently in the group treated with RF-bic ( 7 out of 24 , 29 % ) than in the group treated with RF-lac ( 12 out of 21 , 57 % , P = 0.058 ) . In patients with septic shock , lethality was comparable in both groups ( RF-bic , 10 out of 27 , 37 % ; RF-lac , 7 out of 20 , 35 % , P = NS ) . CONCLUSIONS The results show that the administration of RF-bic solution was superior in normalizing acidosis of patients without the risk of alkalosis . The data also suggest that the use of RF-bic during CVVH reduces cardiovascular events in critically ill patients with acute renal failure , particularly those with previous cardiovascular disease or heart failure Overwhelming evidence shows the quality of reporting of r and omised controlled trials ( RCTs ) is not optimal . Without transparent reporting , readers can not judge the reliability and validity of trial findings nor extract information for systematic review s. Recent method ological analyses indicate that inadequate reporting and design are associated with biased estimates of treatment effects . Such systematic error is seriously damaging to RCTs , which are considered the gold st and ard for evaluating interventions because of their ability to minimise or avoid bias . A group of scientists and editors developed the CONSORT ( Consoli date d St and ards of Reporting Trials ) statement to improve the quality of reporting of RCTs . It was first published in 1996 and up date d in 2001 . The statement consists of a checklist and flow diagram that authors can use for reporting an RCT . Many leading medical journals and major international editorial groups have endorsed the CONSORT statement . The statement facilitates critical appraisal and interpretation of RCTs . During the 2001 CONSORT revision , it became clear that explanation and elaboration of the principles underlying the CONSORT statement would help investigators and others to write or appraise trial reports . A CONSORT explanation and elaboration article was published in 2001 alongside the 2001 version of the CONSORT statement . After an expert meeting in January 2007 , the CONSORT statement has been further revised and is published as the CONSORT 2010 Statement . This up date improves the wording and clarity of the previous checklist and incorporates recommendations related to topics that have only recently received recognition , such as selective outcome reporting bias . This explanatory and elaboration document-intended to enhance the use , underst and ing , and dissemination of the CONSORT statement-has also been extensively revised . It presents the meaning and rationale for each new and up date d checklist item providing examples of good reporting and , where possible , references to relevant empirical studies . Several examples of flow diagrams are included . The CONSORT 2010 Statement , this revised explanatory and elaboration document , and the associated website ( www.consort-statement.org ) should be helpful re sources to improve reporting of r and omised trials |
12,158 | 27,206,947 | This study demonstrates differential changes in OxPL-apoB and Lp(a ) with various lipid-lowering approaches .
These changes in OxPL-apoB and Lp(a ) may provide insights into the results and interpretation of recent cardiovascular disease outcomes trials | BACKGROUND Oxidized phospholipids ( OxPL ) on apolipoprotein B-100 ( OxPL-apoB ) reflect the biological activity of lipoprotein(a ) ( Lp[a ] ) and predict cardiovascular disease events .
However , studies with statins and low-fat diets show increases in OxPL-apoB and Lp(a ) . | CONTEXT High levels of lipoprotein(a ) are associated with increased risk of myocardial infa rct ion ( MI ) . OBJECTIVE To assess whether genetic data are consistent with this association being causal . DESIGN , SETTING , AND PARTICIPANTS Three studies of white individuals from Copenhagen , Denmark , were used : the Copenhagen City Heart Study ( CCHS ) , a prospect i ve general population study with 16 years of follow-up ( 1991 - 2007 , n = 8637 , 599 MI events ) ; the Copenhagen General Population Study ( CGPS ) , a cross-sectional general population study ( 2003 - 2006 , n = 29 388 , 994 MI events ) ; and the Copenhagen Ischemic Heart Disease Study ( CIHDS ) , a case-control study ( 1991 - 2004 , n = 2461 , 1231 MI events ) . MAIN OUTCOME MEASURES Plasma lipoprotein(a ) levels , lipoprotein(a ) kringle IV type 2 ( KIV-2 ) size polymorphism genotype , and MIs recorded from 1976 through July 2007 for all participants . RESULTS In the CCHS , multivariable-adjusted hazard ratios ( HRs ) for MI for elevated lipoprotein(a ) levels were 1.2 ( 95 % confidence interval [ CI ] , 0.9 - 1.6 ; events/10,000 person-years , 59 ) for levels between the 22nd and 66th percentile , 1.6 ( 95 % CI , 1.1 - 2.2 ; events/10,000 person-years , 75 ) for the 67th to 89th percentile , 1.9 ( 95 % CI , 1.2 - 3.0 ; events/10,000 person-years , 84 ) for the 90th to 95th percentile , and 2.6 ( 95 % CI , 1.6 - 4.1 ; events/10,000 person-years , 108 ) for levels greater than the 95th percentile , respectively , vs levels less than the 22nd percentile ( events/10,000 person-years , 55 ) ( trend P < .001 ) . Numbers of KIV-2 repeats ( sum of repeats on both alleles ) ranged from 6 to 99 and on analysis of variance explained 21 % and 27 % of all variation in plasma lipoprotein(a ) levels in the CCHS and CGPS , respectively . Mean lipoprotein(a ) levels were 56 , 31 , 20 , and 15 mg/dL for the first , second , third , and fourth quartiles of KIV-2 repeats in the CCHS , respectively ( trend P < .001 ) ; corresponding values in the CGPS were 60 , 34 , 22 , and 19 mg/dL ( trend P < .001 ) . In the CCHS , multivariable-adjusted HRs for MI were 1.5 ( 95 % CI , 1.2 - 1.9 ; events/10,000 person-years , 75 ) , 1.3 ( 95 % CI , 1.0 - 1.6 ; events/10,000 person-years , 66 ) , and 1.1 ( 95 % CI , 0.9 - 1.4 ; events/10,000 person-years , 57 ) for individuals in the first , second , and third quartiles , respectively , as compared with individuals in the fourth quartile of KIV-2 repeats ( events/10,000 person-years , 51 ) ( trend P < .001 ) . Corresponding odds ratios were 1.3 ( 95 % CI , 1.1 - 1.5 ) , 1.1 ( 95 % CI , 0.9 - 1.3 ) , and 0.9 ( 95 % CI , 0.8 - 1.1 ) in the CGPS ( trend P = .005 ) , and 1.4 ( 95 % CI , 1.1 - 1.7 ) , 1.2 ( 95 % CI , 1.0 - 1.6 ) , and 1.3 ( 95 % CI , 1.0 - 1.6 ) in the CIHDS ( trend P = .01 ) . Genetically elevated lipoprotein(a ) was associated with an HR of 1.22 ( 95 % CI , 1.09 - 1.37 ) per doubling of lipoprotein(a ) level on instrumental variable analysis , while the corresponding value for plasma lipoprotein(a ) levels on Cox regression was 1.08 ( 95 % CI , 1.03 - 1.12 ) . CONCLUSION These data are consistent with a causal association between elevated lipoprotein(a ) levels and increased risk of MI Background —Oxidized phospholipids ( OxPL ) circulate on apolipoprotein B-100 particles ( OxPL/apoB ) , and primarily on Lp(a ) lipoprotein ( a ) [ Lp(a ) ] . The relationship of OxPL/apoB levels to future cardiovascular events is not known . Methods and Results —The Bruneck study is a prospect i ve population -based survey of 40- to 79-year-old men and women recruited in 1990 . Plasma levels of OxPL/apoB and lipoprotein ( a ) [ Lp(a ) ] were measured in 765 subjects in 1995 and incident cardiovascular disease ( CVD ) , defined as cardiovascular death , myocardial infa rct ion , stroke , and transient ischemic attack , was assessed from 1995 to 2005 . During the follow-up period , 82 subjects developed CVD . In multivariable analysis , which included traditional risk factors , high sensitivity C-reactive protein ( hsCRP ) , and lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) activity , subjects in the highest tertile of OxPL/apoB had a significantly higher risk of cardiovascular events than those in the lowest tertile ( hazard ratio[95 % CI ] 2.4[1.3 to 4.3 ] , P=0.004 ) . The strength of the association between OxPL/apoB and CVD risk was amplified with increasing Lp-PLA2 activity ( P=0.018 for interaction ) . Moreover , OxPL/apoB levels predicted future cardiovascular events beyond the information provided by the Framingham Risk Score ( FRS ) . The effects of OxPL/apoB and Lp(a ) were not independent of each other but they were independent of all other measured risk factors . Conclusions —This study demonstrates that OxPL/apoB levels predict 10-year CVD event rates independently of traditional risk factors , hsCRP , and FRS . Increasing Lp-PLA2 activity further amplifies the risk of CVD mediated by BACKGROUND Oxidized phospholipids on apolipoprotein B-100 ( OxPL-apoB ) is a biomarker of increased risk for major adverse cardiovascular events ( MACE ) in community cohorts , but its role in patients with stable coronary heart disease ( CHD ) is unknown . OBJECTIVES This study sought to examine the relationship between these oxidative biomarkers and cardiovascular outcomes in patients with established CHD . METHODS In a r and om sample from the TNT ( Treating to New Targets ) trial , OxPL-apoB levels were measured in 1,503 patients at r and omization ( after an 8-week run-in period taking atorvastatin 10 mg ) and 1 year after being r and omized to atorvastatin 10 or 80 mg . We examined the association between baseline levels of OxPL-apoB and MACE , defined as death from CHD , nonfatal myocardial infa rct ion , resuscitation after cardiac arrest , and fatal/nonfatal stroke , as well as the effect of statin therapy on OxPL-apoB levels and MACE . RESULTS Patients with events ( n = 156 ) had higher r and omization levels of OxPL-apoB than those without events ( p = 0.025 ) . For the overall cohort , r and omization levels of OxPL-apoB predicted subsequent MACE ( hazard ratio [ HR ] : 1.21 ; 95 % confidence interval : 1.04 to 1.41 ; p = 0.018 ) per doubling and tertile 3 versus tertile 1 ( hazard ratio : 1.69 ; 95 % confidence interval [ CI ] : 1.14 to 2.49 ; p = 0.01 ) after multivariate adjustment for age , sex , body mass index , among others , and treatment assignment . In the atorvastatin 10-mg group , tertile 3 was associated with a higher risk of MACE compared to the first tertile ( HR : 2.08 ; 95 % CI : 1.20 to 3.61 ; p = 0.01 ) but this was not significant in the atorvastatin 80-mg group ( HR : 1.40 ; 95 % CI : 0.80 to 2.46 ; p = 0.24 ) . CONCLUSIONS Elevated OxPL-apoB levels predict secondary MACE in patients with stable CHD , a risk that is mitigated by atorvastatin 80 mg . ( A Study to Determine the Degree of Additional Reduction in CV Risk in Lowering LDL Below Minimum Target Levels [ TNT ] ; NCT00327691 ) OBJECTIVES The aim of this study was to determine the effects of pravastatin and atorvastatin on markers of oxidative stress in plasma . BACKGROUND Hydroxymethylglutaryl coenzyme A reductase inhibitors reduce low-density lipoprotein cholesterol ( LDL-C ) and cardiovascular risk , but their effects on circulating biomarkers of oxidative stress are not well-defined . METHODS Hypercholesterolemic subjects ( n = 120 , ages 21 to 80 years with LDL-C 130 to 220 mg/dl ) were r and omized in a double-blind , parallel design to pravastatin 40 mg/day ( prava40 ) , atorvastatin 10 mg/day ( atorva10 ) , atorvastatin 80 mg/day ( atorva80 ) , or placebo . At baseline and 16 weeks , urinary isoprostanes ( 8 , 12-iso-iPF(2 alpha)-VI isoform ) , plasma lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , Mercodia oxidized LDL ( OxLDL ) with antibody 4E6 , oxidized phospholipids/apolipoprotein B-100 particle ( OxPL/apoB ) with antibody E06 , immunoglobulin (Ig)G/IgM autoantibodies to malondialdehyde (MDA)-LDL , and apolipoprotein B (apoB)-immune complexes ( IC ) were measured . RESULTS After 16 weeks , there were no significant changes in urinary 8 , 12-iso-iPF(2 alpha)-VI . The Lp-PLA2 and OxLDL were reduced in statin-treated groups , but after adjusting for apoB , only prava40 led to a reduction in Lp-PLA2 ( -15 % , p = 0.008 ) and atorva10 to a decrease in OxLDL ( -12.9 % , p = 0.01 ) . The OxPL/apoB increased 25.8 % ( p < 0.01 ) with prava40 and 20.2 % ( p < 0.05 ) with atorva80 . There were no changes in MDA-LDL autoantibodies , but significant decreases in IC were noted . CONCLUSIONS This study suggests that statin therapy results in variable effects on oxidative stress markers in hypercholesterolemic subjects . Future outcome studies should collectively assess various oxidative markers to define clinical utility BACKGROUND Lipoprotein(a ) ( Lp[a ] ) is a risk factor for cardiovascular disease and calcific aortic valve stenosis . No effective therapies to lower plasma Lp(a ) concentrations exist . We have assessed the safety , pharmacokinetics , and pharmacodynamics of ISIS-APO(a)Rx , a second-generation antisense drug design ed to reduce the synthesis of apolipoprotein(a ) ( apo[a ] ) in the liver . METHODS In this r and omised , double-blind , placebo-controlled , phase 1 study at the PAREXEL Clinical Pharmacology Research Unit ( Harrow , Middlesex , UK ) , we screened for healthy adults aged 18 - 65 years , with a body-mass index less than 32·0 kg/m(2 ) , and Lp(a ) concentration of 25 nmol/L ( 100 mg/L ) or more . Via a r and omisation technique , we r and omly assigned participants to receive a single subcutaneous injection of ISIS-APO(a)Rx ( 50 mg , 100 mg , 200 mg , or 400 mg ) or placebo ( 3:1 ) in the single-dose part of the study or to receive six subcutaneous injections of ISIS-APO(a)Rx ( 100 mg , 200 mg , or 300 mg , for a total dose exposure of 600 mg , 1200 mg , or 1800 mg ) or placebo ( 4:1 ) during a 4 week period in the multi-dose part of the study . Participants , investigators , and study staff were masked to the treatment assignment , except for the pharmacist who prepared the ISIS-APO(a)Rx or placebo . The primary efficacy endpoint was the percentage change from baseline in Lp(a ) concentration at 30 days in the single-dose cohorts and at 36 days for the multi-dose cohorts . Safety and tolerability was assessed 1 week after last dose and included determination of the incidence , severity , and dose relation of adverse events and changes in laboratory variables , including lipid panel , routine haematology , blood chemistry , urinalysis , coagulation , and complement variables . Other assessment s included vital signs , a physical examination , and 12-lead electrocardiograph . This trial is registered with European Clinical Trials Data base , number 2012 - 004909 - 27 . FINDINGS Between Feb 27 , 2013 , and July 15 , 2013 , 47 ( 23 % ) of 206 screened volunteers were r and omly assigned to receive ISIS-APO(a)Rx as a single-dose or multi-dose of ascending concentrations or placebo . In the single-dose study , we assigned three participants to receive 50 mg ISIS-APO(a)Rx , three participants to receive 100 mg ISIS-APO(a)Rx , three participants to receive 200 mg ISIS-APO(a)Rx , three participants to receive 400 mg ISIS-APO(a)Rx , and four participants to receive placebo . All 16 participants completed treatment and follow-up and were included in the pharmacodynamics , pharmacokinetics , and safety analyses . For the multi-dose study , we assigned eight participants to receive six doses of 100 mg ISIS-APO(a)Rx , nine participants to receive six doses of 200 mg ISIS-APO(a)Rx , eight participants to receive six doses of 300 mg ISIS-APO(a)Rx , and six participants to receive six doses of placebo . Whereas single doses of ISIS-APO(a)Rx ( 50 - 400 mg ) did not decrease Lp(a ) concentrations at day 30 , six doses of ISIS-APO(a)Rx ( 100 - 300 mg ) result ed in dose-dependent , mean percentage decreases in plasma Lp(a ) concentration of 39·6 % from baseline in the 100 mg group ( p=0·005 ) , 59·0 % in the 200 mg group ( p=0·001 ) , and 77·8 % in the 300 mg group ( p=0·001 ) . Similar reductions were observed in the amount of oxidized phospholipids associated with apolipoprotein B-100 and apolipoprotein(a ) . Mild injection site reactions were the most common adverse events . INTERPRETATION ISIS-APO(a)Rx results in potent , dose-dependent , selective reductions of plasma Lp(a ) . The safety and tolerability support continued clinical development of ISIS-APO(a)Rx as a potential therapeutic drug to reduce the risk of cardiovascular disease and calcific aortic valve stenosis in patients with elevated Lp(a ) concentration . FUNDING Isis Pharmaceuticals BACKGROUND Anacetrapib is a cholesteryl ester transfer protein inhibitor that raises high-density lipoprotein ( HDL ) cholesterol and reduces low-density lipoprotein ( LDL ) cholesterol . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to assess the efficacy and safety profile of anacetrapib in patients with coronary heart disease or at high risk for coronary heart disease . Eligible patients who were taking a statin and who had an LDL cholesterol level that was consistent with that recommended in guidelines were assigned to receive 100 mg of anacetrapib or placebo daily for 18 months . The primary end points were the percent change from baseline in LDL cholesterol at 24 weeks ( HDL cholesterol level was a secondary end point ) and the safety and side-effect profile of anacetrapib through 76 weeks . Cardiovascular events and deaths were prospect ively adjudicated . RESULTS A total of 1623 patients underwent r and omization . By 24 weeks , the LDL cholesterol level had been reduced from 81 mg per deciliter ( 2.1 mmol per liter ) to 45 mg per deciliter ( 1.2 mmol per liter ) in the anacetrapib group , as compared with a reduction from 82 mg per deciliter ( 2.1 mmol per liter ) to 77 mg per deciliter ( 2.0 mmol per liter ) in the placebo group (P<0.001)--a 39.8 % reduction with anacetrapib beyond that seen with placebo . In addition , the HDL cholesterol level increased from 41 mg per deciliter ( 1.0 mmol per liter ) to 101 mg per deciliter ( 2.6 mmol per liter ) in the anacetrapib group , as compared with an increase from 40 mg per deciliter ( 1.0 mmol per liter ) to 46 mg per deciliter ( 1.2 mmol per liter ) in the placebo group (P<0.001)--a 138.1 % increase with anacetrapib beyond that seen with placebo . Through 76 weeks , no changes were noted in blood pressure or electrolyte or aldosterone levels with anacetrapib as compared with placebo . Prespecified adjudicated cardiovascular events occurred in 16 patients treated with anacetrapib ( 2.0 % ) and 21 patients receiving placebo ( 2.6 % ) ( P = 0.40 ) . The prespecified Bayesian analysis indicated that this event distribution provided a predictive probability ( confidence ) of 94 % that anacetrapib would not be associated with a 25 % increase in cardiovascular events , as seen with torcetrapib . CONCLUSIONS Treatment with anacetrapib had robust effects on LDL and HDL cholesterol , had an acceptable side-effect profile , and , within the limits of the power of this study , did not result in the adverse cardiovascular effects observed with torcetrapib . ( Funded by Merck Research Laboratories ; Clinical Trials.gov number , NCT00685776 . ) Background —Oxidized phospholipids ( OxPL ) are present within atherosclerotic plaques and bound by lipoprotein ( a ) [ Lp(a ) ] in plasma . This study evaluated the impact of atorvastatin on oxidized LDL ( OxLDL ) in patients with acute coronary syndromes ( ACS ) . Methods and Results —OxLDL-E06 ( OxPL content on apolipoprotein B-100 [ apoB ] detected by antibody E06 ) , apoB-100 immune complexes ( apoB-IC ) , OxLDL autoantibodies , and Lp(a ) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo . The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle ( OxPL/apoB , IC/apoB ) and as total levels on all apoB-100 particles ( total apoB-OxPL and total apoB-IC [ eg , OxPL/apoB or IC/apoB × apoB-100 levels ] ) . Compared with baseline values , atorvastatin reduced apoB-100 ( −33 % ) , total apoB-OxPL ( −29.7 % ) , total apoB-IC IgG ( −29.5 % ) , and IgM ( −25.7 % ) ( P<0.0001 for all ) , whereas no change or an increase was observed with placebo . When normalized per apoB-100 , compared with placebo , atorvastatin increased OxPL/apoB ( 9.5 % versus −3.9 % , P<0.0001 ) and Lp(a ) ( 8.8 % versus −0.7 % , ( P<0.0001 ) . A strong correlation was noted between OxPL/apoB and Lp(a ) ( R=0.85 , P<0.0001 ) , consistent with previous data that Lp(a ) binds OxPL . Conclusions —After atorvastatin treatment , total OxPL on all apoB-100 particles was decreased . However , there was enrichment of OxPL on a smaller pool of apoB-100 particles , in parallel with similar increases in Lp(a ) , suggesting binding by Lp(a ) . These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL , which may contribute to a reduction in ischemic events after ACS OBJECTIVES This study evaluated the safety and lipid-altering efficacy of ezetimibe/simvastatin ( E/S ) coadministered with extended-release niacin ( N ) in patients with type IIa or IIb hyperlipidemia . BACKGROUND Current guidelines recommend consideration of combination drug therapy to achieve optimal low-density lipoprotein cholesterol ( LDL-C ) lowering and broader lipid-altering effects when treating hypercholesterolemic patients at high risk for atherosclerotic cardiovascular events . METHODS In this 24-week multicenter , r and omized , double-blind study , 1,220 type IIa or IIb hyperlipidemic patients were r and omized to treatment with E/S ( 10/20 mg/day ) + N ( titrated to 2 g/day ) , or N ( titrated to 2 g/day ) , or E/S ( 10/20 mg/day ) . Changes from baseline in LDL-C ( primary ) and other secondary variables were assessed in the completers and modified intent-to-treat population s. RESULTS Coadministered E/S with N result ed in significantly greater reductions in LDL-C , non-high-density lipoprotein cholesterol , triglycerides , apolipoprotein B , and lipid/lipoprotein ratios , compared with either agent alone ( p < 0.001 ) . The combination increased levels of apolipoprotein A-I and high-density lipoprotein cholesterol significantly more than E/S ( p < 0.001 ) , and reduced high-sensitivity C-reactive protein levels significantly more than N ( p = 0.005 ) . A significantly greater percentage of patients discontinued the study in the N ( 25.0 % ) and N + E/S ( 23.3 % ) groups , compared with E/S ( 9.6 % , p < 0.001 ) because of clinical adverse experiences ( primarily flushing ) . Incidences of other clinical and laboratory adverse experiences ( liver- , muscle- , and gastrointestinal-related ) were similar for all groups . CONCLUSIONS Combination treatment with E/S plus N showed superior lipid-altering efficacy compared with N or E/S in type IIa or IIb hyperlipidemia patients and was generally well tolerated aside from N-associated flushing . This combination offers an effective , broad , lipid-altering therapy with improvements in lipid effects beyond LDL-C in these patients . ( To Evaluate Ezetimibe/Simvastatin and Niacin [ Extended Release Tablet ] in Patients With High Cholesterol OBJECTIVES This study was conducted to test the hypothesis that plasma markers of oxidized low-density lipoprotein ( OxLDL ) reflect acute coronary syndromes ( ACS ) . BACKGROUND Oxidized LDL contributes to the pathogenesis of atherosclerosis , but its role in ACS is not established . METHODS Serial plasma sample s were prospect ively obtained from patients with an acute myocardial infa rct ion ( MI ) ( n = 8) , unstable angina ( UA ) ( n = 15 ) , stable coronary artery disease ( CAD ) ( n = 17 ) , angiographically normal coronary arteries ( n = 8) , and from healthy subjects ( n = 18 ) , at entry into the study , hospital discharge ( MI group only ) , and at 30 , 120 , and 210 days . Chemiluminescent enzyme-linked immunosorbent assay was used to quantitate plasma levels of : 1 ) immunoglobulin (Ig)M and IgG OxLDL autoantibody titers ( presented as a mean OxLDL autoantibody titer by averaging the results of four distinct epitopes ) ; 2 ) LDL-autoantibody immune complexes ( LDL-IC ) ; and 3 ) minimally OxLDL measured by antibody E06 ( OxLDL-E06 ) , as determined by the content of oxidized phospholipids ( OxPL ) per apolipoprotein B-100 . RESULTS Baseline OxLDL IgG autoantibody levels were higher in the MI group ( p < 0.0001 ) . At 30-day follow-up , the mean IgM OxLDL titers increased by 48 % ( p < 0.001 ) and 20 % ( p < 0.001 ) , and IgM LDL-IC increased by 60 % ( p < 0.01 ) and 26 % ( p < 0.01 ) in the MI and UA groups , respectively . The OxLDL-E06 levels increased by 54 % ( p < 0.01 ) in the MI group at hospital discharge and by 36 % at 30 days . No significant changes in any OxLDL markers were noted in the other groups . The OxLDL-E06 levels strongly paralleled the acute rise in lipoprotein(a ) , or Lp(a ) , in the MI group , suggesting that toxic OxPL are preferentially bound to Lp(a ) . Oxidized LDL-E06 also correlated extremely well with Lp(a ) in the entire cohort of patients ( r = 0.91 , p < 0.0001 ) . CONCLUSIONS Circulating OxLDL-specific markers strongly reflect the presence of ACS , implying immune awareness to newly exposed oxidation-specific epitopes and possible release of OxLDL in the circulation . The OxLDL-E06 measurements provide novel insights into plaque rupture and the potential atherogenicity of Lp(a ) OBJECTIVES Previous studies demonstrated that aged garlic extract reduces multiple cardiovascular risk factors . This study was design ed to assess whether aged garlic extract therapy with supplements ( AGE+S ) favorably affects inflammatory and oxidation biomarkers , vascular function and progression of atherosclerosis as compared to placebo . METHODS In this placebo-controlled , double-blind , r and omized trial ( conducted 2005 - 2007 ) , 65 intermediate risk patients ( age 60+/-9 years , 79 % male ) were treated with a placebo capsule or a capsule containing aged garlic extract ( 250 mg ) plus Vitamin B12 ( 100 microg ) , folic acid ( 300 microg ) , Vitamin B6 ( 12.5 mg ) and l-arginine ( 100 mg ) given daily for a 1 year . All patients underwent coronary artery calcium scanning ( CAC ) , temperature rebound ( TR ) as an index of vascular reactivity using Digital Thermal Monitoring ( DTM ) , and measurement of lipid profile , autoantibodies to malondialdehyde (MDA)-LDL , apoB-immune complexes , oxidized phospholipids ( OxPL ) on apolipoprotein B-100 ( OxPL/apoB ) , lipoprotein ( a ) [ Lp ( a ) ] , C-reactive protein ( CRP ) , homocysteine were measured at baseline and 12 months . CAC progression was defined as an increase in CAC>15 % per year and an increase in TR above baseline was considered a favorable response . RESULTS At 1 year , CAC progression was significantly lower and TR significantly higher in the AGE+S compared to the placebo group after adjustment of cardiovascular risk factors ( p<0.05 ) . Total cholesterol , LDL-C , homocysteine , IgG and IgM autoantibodies to MDA-LDL and apoB-immune complexes were decreased , whereas HDL , OxPL/apoB , and Lp ( a ) were significantly increased in AGE+S to placebo . CONCLUSION AGE+S is associated with a favorable improvement in oxidative biomarkers , vascular function , and reduced progression of atherosclerosis BACKGROUND In patients with established cardiovascular disease , residual cardiovascular risk persists despite the achievement of target low-density lipoprotein ( LDL ) cholesterol levels with statin therapy . It is unclear whether extended-release niacin added to simvastatin to raise low levels of high-density lipoprotein ( HDL ) cholesterol is superior to simvastatin alone in reducing such residual risk . METHODS We r and omly assigned eligible patients to receive extended-release niacin , 1500 to 2000 mg per day , or matching placebo . All patients received simvastatin , 40 to 80 mg per day , plus ezetimibe , 10 mg per day , if needed , to maintain an LDL cholesterol level of 40 to 80 mg per deciliter ( 1.03 to 2.07 mmol per liter ) . The primary end point was the first event of the composite of death from coronary heart disease , nonfatal myocardial infa rct ion , ischemic stroke , hospitalization for an acute coronary syndrome , or symptom-driven coronary or cerebral revascularization . RESULTS A total of 3414 patients were r and omly assigned to receive niacin ( 1718 ) or placebo ( 1696 ) . The trial was stopped after a mean follow-up period of 3 years owing to a lack of efficacy . At 2 years , niacin therapy had significantly increased the median HDL cholesterol level from 35 mg per deciliter ( 0.91 mmol per liter ) to 42 mg per deciliter ( 1.08 mmol per liter ) , lowered the triglyceride level from 164 mg per deciliter ( 1.85 mmol per liter ) to 122 mg per deciliter ( 1.38 mmol per liter ) , and lowered the LDL cholesterol level from 74 mg per deciliter ( 1.91 mmol per liter ) to 62 mg per deciliter ( 1.60 mmol per liter ) . The primary end point occurred in 282 patients in the niacin group ( 16.4 % ) and in 274 patients in the placebo group ( 16.2 % ) ( hazard ratio , 1.02 ; 95 % confidence interval , 0.87 to 1.21 ; P=0.79 by the log-rank test ) . CONCLUSIONS Among patients with atherosclerotic cardiovascular disease and LDL cholesterol levels of less than 70 mg per deciliter ( 1.81 mmol per liter ) , there was no incremental clinical benefit from the addition of niacin to statin therapy during a 36-month follow-up period , despite significant improvements in HDL cholesterol and triglyceride levels . ( Funded by the National Heart , Lung , and Blood Institute and Abbott Laboratories ; AIM -HIGH Clinical Trials.gov number , NCT00120289 . ) OBJECTIVE The effects of potent statins on oxidized lipoprotein biomarkers are not well defined . METHODS AND RESULTS The VISION ( Value of oxIdant lipid lowering effect by Statin InterventiON in hypercholesterolemia ) Trial r and omized patients with hypercholesterolemia to 12-week administration of pitavastatin 2 mg/day ( n = 21 ) or atorvastatin 10 mg/day ( n = 21 ) and a variety of lipoprotein oxidative biomarkers were measured . Between-group analysis did not reveal any differences except in the ratio of malondialdehyde (MDA)-LDL over apolipoprotein B-100 ( MDA-LDL/apoB ) in pitavastatin vs. atorvastatin group ( -13 % vs. -0.7 % , p = 0.04 ) . Within-group changes from baseline to 12-week revealed significant increases in OxPL/apoB and reductions in small-dense LDL , MDA-LDL , and lipoprotein-associated phospholipase A(2 ) measured on circulating apoB particles ( Lp-PLA(2)/apoB ) in both groups and significant reductions in OxPL/apoAI in the atorvastatin group . CONCLUSIONS The VISION study describes the first comparison on lipoprotein oxidation biomarkers between pitavastatin and atorvastatin and suggests diverse effects on lipoprotein oxidation markers in patients with hypercholesterolemia Lipoprotein ( a ) [ Lp(a ) ] is a highly atherogenic lipid particle . Although earlier reports suggested that Lp(a ) levels are mostly determined by genetic factors , several recent studies have revealed that Lp(a ) induction is also caused by chronic inflammation . Therefore , we aim ed to examine whether cytokine blockade by monoclonal antibodies may inhibit Lp(a ) metabolism . We found that interleukin 6 ( IL-6 ) blockade by tocilizumab ( TCZ ) reduced Lp(a ) while TNF-α-inhibition by adalimumab in humans had no effect . The specificity of IL-6 in regulating Lp(a ) was further demonstrated by serological measurements of human subjects ( n = 1,153 ) revealing that Lp(a ) levels are increased in individuals with elevated serum IL-6 . Transcriptomic analysis of human liver biopsies ( n = 57 ) revealed typical IL-6 response genes being correlated with the LPA gene expression in vivo . On a molecular level , we found that TCZ inhibited IL-6-induced LPA mRNA and protein expression in human hepatocytes . Furthermore , examination of IL-6-responsive signal transducer and activator of transcription 3 binding sites within the LPA promoter by reporter gene assays , promoter deletion experiments , and electrophoretic mobility shift assay analysis showed that the Lp(a)-lowering effect of TCZ is specifically mediated via a responsive element at −46 to −40 . Therefore , IL-6 blockade might be a potential therapeutic option to treat elevated Lp(a ) serum concentrations in humans and might be a noninvasive alternative to lipid apheresis in the future OBJECTIVES The purpose of this work was to determine the predictive value of oxidized phospholipids ( OxPLs ) present on apolipoprotein B-100 particles ( apoB ) in carotid and femoral atherosclerosis . BACKGROUND The OxPLs are pro-inflammatory and pro-atherogenic and may be detected using the antibody E06 ( OxPL/apoB ) . METHODS The Bruneck study is a prospect i ve population -based survey of 40- to 79-year-old men and women initiated in 1990 . Plasma levels of OxPL/apoB and lipoprotein ( a ) [ Lp(a ) ] were measured in 765 of 826 ( 92.6 % ) and 671 of 684 ( 98.1 % ) subjects alive in 1995 and 2000 , respectively , and correlated with ultrasound measures of carotid and femoral atherosclerosis . RESULTS The distribution of the OxPL/apoB levels was skewed to lower levels and nearly identical to Lp(a ) levels . The OxPL/apoB and Lp(a ) levels were highly correlated ( r = 0.87 , p < 0.001 ) , and displayed long-term stability and lacked correlations with most cardiovascular risk factors and lifestyle variables . The number of apolipoprotein ( a ) kringle IV-2 repeats was inversely related to Lp(a ) mass ( r = -0.48 , p < 0.001 ) and OxPL/apoB levels ( r = -0.46 , p < 0.001 ) . In multivariable analysis , OxPL/apoB levels were strongly and significantly associated with the presence , extent , and development ( 1995 to 2000 ) of carotid and femoral atherosclerosis and predicted the presence of symptomatic cardiovascular disease . Both OxPL/apoB and Lp(a ) levels showed similar associations with atherosclerosis severity and progression , suggesting a common biological influence on atherogenesis . CONCLUSIONS This study suggests that pro-inflammatory oxidized phospholipids , present primarily on Lp(a ) , are significant predictors of the presence and extent of carotid and femoral atherosclerosis , development of new lesions , and increased risk of cardiovascular events . The OxPL biomarkers may provide valuable insights into diagnosing and monitoring cardiovascular disease The safety and efficacy of combination ezetimibe/simvastatin ( E/S ) plus extended-release niacin was assessed in 942 patients with type IIa/IIb hyperlipidemia for 64 weeks in a r and omized , double-blind study . Patients received E/S ( 10/20 mg ) plus niacin ( to 2 g ) or E/S ( 10/20 mg ) for 64 weeks , or niacin ( to 2 g ) for 24 weeks and then E/S ( 10/20 mg ) plus niacin ( 2 g ) or E/S ( 10/20 mg ) for an additional 40 weeks . The primary end point , the safety of E/S plus niacin , included prespecified adverse events ( ie , liver , muscle , discontinuations due to flushing , gallbladder-related , cholecystectomy , fasting glucose changes , new-onset diabetes ) . The secondary end points included the percentage of change from baseline in high-density lipoprotein ( HDL ) cholesterol , triglycerides , non-HDL cholesterol , and low-density lipoprotein cholesterol , other lipids , lipoprotein ratios and high-sensitivity C-reactive protein . The anticipated niacin-associated flushing led to a greater rate of study discontinuations with the E/S plus niacin regimen than with E/S alone ( 0.7 % , p < 0.001 ) . The rate of liver and muscle adverse events was low ( < 1 % ) in both groups . Four patients had gallbladder-related adverse events ; 1 patient in the E/S and 1 in the E/S plus niacin group underwent cholecystectomy . The occurrence of new-onset diabetes was 3.1 % for the E/S and 4.9 % for the E/S plus niacin group . The fasting glucose levels increased to greater than baseline during the first 12 weeks ( E/S , 3.2 mg/dl ; E/S plus niacin , 7.7 mg/dl ) and gradually decreased to pretreatment levels by 64 weeks in both groups . E/S plus niacin significantly improved HDL cholesterol , triglycerides , non-HDL cholesterol , low-density lipoprotein cholesterol , apolipoprotein B and A-I , and lipoprotein ratios compared with E/S ( p < or=0.004 ) . The changes in high-sensitivity C-reactive protein were comparable for both groups . In conclusion , the combination of E/S plus niacin was generally well tolerated , aside from niacin-associated flushing , and was significantly superior to E/S alone in improving several lipoprotein parameters during a 64-week trial in patients with hyperlipidemia . E/S plus niacin provided a broad , lipid-altering therapeutic option for these patients , even in the presence of diabetes with glucose monitoring Low-fat diets have been shown to increase plasma concentrations of lipoprotein(a ) [ Lp(a ) ] , a preferential lipoprotein carrier of oxidized phospholipids ( OxPLs ) in plasma , as well as small dense LDL particles . We sought to determine whether increases in plasma Lp(a ) induced by a low-fat high-carbohydrate ( LFHC ) diet are related to changes in OxPL and LDL subclasses . We studied 63 healthy subjects after 4 weeks of consuming , in r and om order , a high-fat low-carbohydrate ( HFLC ) diet and a LFHC diet . Plasma concentrations of Lp(a ) ( P < 0.01 ) , OxPL/apolipoprotein (apo)B ( P < 0.005 ) , and OxPL-apo(a ) ( P < 0.05 ) were significantly higher on the LFHC diet compared with the HFLC diet whereas LDL peak particle size was significantly smaller ( P < 0.0001 ) . Diet-induced changes in Lp(a ) were strongly correlated with changes in OxPL/apoB ( P < 0.0001 ) . The increases in plasma Lp(a ) levels after the LFHC diet were also correlated with decreases in medium LDL particles ( P < 0.01 ) and increases in very small LDL particles ( P < 0.05 ) . These results demonstrate that induction of increased levels of Lp(a ) by an LFHC diet is associated with increases in OxPLs and with changes in LDL subclass distribution that may reflect altered metabolism of Lp(a ) particles OBJECTIVES To assess the role of oxidized phospholipids ( OxPLs ) in children with familial hypercholesterolemia ( FH ) and the effect of pravastatin . BACKGROUND Oxidized phospholipids are a major component of oxidized low-density lipoprotein ( OxLDL ) and are bound to lipoprotein ( a ) [ Lp(a ) ] . The significance of OxPL markers in children is unknown . METHODS Children with FH were r and omized to placebo ( n = 88 ) or pravastatin ( n = 90 ) after instruction on American Heart Association step II diet . Unaffected siblings ( n = 78 ) served as controls . The OxPL content on apolipoprotein B-100 ( apoB ) detected by antibody E06 ( OxPL/apoB ratio ) , immunoglobulin (Ig)G and IgM immune complexes per apoB ( IC/apoB ) and on all apoB particles ( total apoB-IC = IC/apoB multiplied by plasma apoB levels ) , autoantibodies to malondialdehyde (MDA)-low-density lipoprotein ( LDL ) , Lp(a ) , and apoB levels were measured at baseline and after two years of treatment . RESULTS Compared with unaffected siblings , children with FH had significantly lower levels of OxPL/apoB but higher levels of IgG and IgM total apoB-IC and IgM MDA-LDL autoantibodies . From baseline to two-year follow-up , compared with placebo pravastatin treatment result ed in a greater mean percentage change in apoB ( -18.7 % vs. 0.3 % ; p = 0.001 ) , total IgG apoB-IC ( -31.9 % vs. -12.2 % ; p < 0.001 ) , and total IgM apoB-IC ( -25.5 % vs. 13.2 % ; p = 0.001 ) . Interestingly , pravastatin also result ed in higher OxPL/apoB ( 48.7 % vs. 29.3 % ; p = 0.028 ) and Lp(a ) levels ( 21.9 % vs. 10.7 % ; p = 0.044 ) . CONCLUSIONS Compared with unaffected siblings , children with FH are characterized by elevated levels of apoB-IC and IgM MDA-LDL autoantibodies . Compared with placebo , pravastatin led to a greater reduction in apoB-IC but also to a greater increase in OxPL/apoB and Lp(a ) , which may represent a novel mechanism of mobilization and clearance of OxPL The relation between oxidative stress and coronary artery calcium ( CAC ) progression is currently not well described . The present study evaluated the relation among the biomarkers of oxidative stress , vascular dysfunction , and CAC . Sixty asymptomatic subjects participated in a r and omized trial evaluating the effect of aged garlic extract plus supplement versus placebo and underwent measurement of CAC . The postcuff deflation temperature-rebound index of vascular function was assessed using a reactive hyperemia procedure . The content of oxidized phospholipids ( OxPL ) on apolipoprotein B-100 ( apoB ) particles detected by antibody E06 ( OxPL/apoB ) , lipoprotein(a ) , IgG and IgM autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes were measured at baseline and after 12 months of treatment . CAC progression was defined as an annual increase in CAC > 15 % . Vascular dysfunction was defined according to the tertiles of temperature-rebound at 1 year of follow-up . From baseline to 12 months , a strong inverse correlation was noted between an increase in CAC scores and increases in temperature-rebound ( r(2 ) = -0.90 ) , OxPL/apoB ( r(2 ) = -0.85 ) , and lipoprotein(a ) ( r(2 ) = -0.81 ) levels ( p < 0.0001 for all ) . The improvement in temperature-rebound correlated positively with the increases in OxPL/apoB ( r(2 ) = 0.81 , p = 0.0008 ) and lipoprotein(a ) ( r(2 ) = 0.79 , p = 0.0001 ) but inversely with autoantibodies to malondialdehyde-low-density lipoprotein and apoB-immune complexes . The greatest CAC progression was noted with the lowest tertiles of increases in temperature-rebound , OxPL/apoB and lipoprotein(a ) and the highest tertiles of increases in IgG and IgM malondialdehyde-low-density lipoprotein . In conclusion , the present results have documented a strong relation among markers of oxidative stress , vascular dysfunction , and progression of coronary atherosclerosis . Increases in OxPL/apoB and lipoprotein(a ) correlated strongly with increases in vascular function and predicted a lack of progression of CAC OBJECTIVES This study sought to assess whether oxidation-specific biomarkers are associated with an increased risk of coronary artery disease ( CAD ) events . BACKGROUND The relationship of a panel of oxidative biomarkers and lipoprotein(a ) [ Lp(a ) ] to CAD risk is not fully determined . METHODS A prospect i ve case-control study nested in the EPIC ( European Prospect i ve Investigation of Cancer)-Norfolk cohort of 45- to 79-year-old apparently healthy men and women followed for approximately 6 years was design ed . Cases consisted of participants in whom fatal or nonfatal CAD developed , matched by sex , age , and enrollment time with controls without CAD . Baseline levels of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a ) were measured in 763 cases and 1,397 controls . Their relationship to secretory phospholipase A(2 ) type IIA mass and activity , myeloperoxidase mass , and lipoprotein-associated phospholipase A(2 ) activity and association with CAD events were determined . RESULTS After adjusting for age , smoking , diabetes , low- and high-density lipoprotein cholesterol , and systolic blood pressure , the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles and Lp(a ) were associated with a significantly higher risk of CAD events ( odds ratios : 1.67 and 1.64 , respectively ; p < 0.001 ) compared with the lowest tertiles . The odds ratio of CAD events associated with the highest tertiles of oxidized phospholipids on apolipoprotein B-100 particles or Lp(a ) was significantly potentiated ( approximately doubled ) by the highest tertiles of secretory phospholipase A(2 ) activity and mass but less so for myeloperoxidase and lipoprotein-associated phospholipase A(2 ) activity . The odds ratios for fatal CAD were higher than for the combined end point . After taking into account the Framingham Risk Score , c-index values progressively increased when oxidative biomarkers were added to the model . CONCLUSIONS This EPIC-Norfolk study links pathophysiologically related oxidation-specific biomarkers and Lp(a ) with CAD events . Oxidation-specific biomarkers provide cumulative predictive value when added to traditional cardiovascular risk factors OBJECTIVES The goal of this study was to examine the prospect i ve association between oxidation-specific biomarkers , primarily oxidized phospholipids ( OxPL ) on apolipoprotein B-100-containing lipoproteins ( OxPL/apoB ) and lipoprotein ( a ) [ Lp(a ) ] , and risk of peripheral artery disease ( PAD ) . We examined , as secondary analyses , indirect measures of oxidized lipoproteins , including autoantibodies to malondialdehyde-modified low-density lipoprotein ( MDA-LDL ) and apolipoprotein B-100 immune complexes ( ApoB-IC ) . BACKGROUND Biomarkers to predict the development of PAD are lacking . OxPL circulate in plasma , are transported by Lp(a ) , and deposit in the vascular wall and induce local inflammation . METHODS The study population included 2 parallel nested case-control studies of 143 men within the Health Professionals Follow-up Study ( 1994 to 2008 ) and 144 women within the Nurses ' Health Study ( 1990 to 2010 ) with incident confirmed cases of clinical ly significant PAD , matched 1:3 to control subjects . RESULTS Levels of OxPL/apoB were positively associated with risk of PAD in men and women : pooled relative risk : 1.37 , 95 % confidence interval : 1.19 to 1.58 for each 1-SD increase after adjusting age , smoking , fasting status , month of blood draw , lipids , body mass index , and other cardiovascular disease risk factors . Lp(a ) was similarly associated with risk of PAD ( pooled adjusted relative risk : 1.36 ; 95 % confidence interval : 1.18 to 1.57 for each 1-SD increase ) . Autoantibodies to MDA-LDL and ApoB-IC were not consistently associated with risk of PAD . CONCLUSIONS OxPL/apoB were positively associated with risk of PAD in men and women . The major lipoprotein carrier of OxPL , Lp(a ) , was also associated with risk of PAD , reinforcing the key role of OxPL in the pathophysiology of atherosclerosis mediated by Lp(a ) BACKGROUND Elevated lipoprotein(a ) ( Lp[a ] ) is associated with aortic stenosis ( AS ) . Oxidized phospholipids ( OxPL ) are key mediators of calcification in valvular cells and are carried by Lp(a ) . OBJECTIVES This study sought to determine whether Lp(a ) and OxPL are associated with hemodynamic progression of AS and AS-related events . METHODS OxPL on apolipoprotein B-100 ( OxPL-apoB ) , which reflects the biological activity of Lp(a ) , and Lp(a ) levels were measured in 220 patients with mild-to-moderate AS . The primary endpoint was the progression rate of AS , measured by the annualized increase in peak aortic jet velocity in m/s/year by Doppler echocardiography ; the secondary endpoint was need for aortic valve replacement and cardiac death during 3.5 ± 1.2 years of follow-up . RESULTS AS progression was faster in patients in the top tertiles of Lp(a ) ( peak aortic jet velocity : + 0.26 ± 0.26 vs. + 0.17 ± 0.21 m/s/year ; p = 0.005 ) and OxPL-apoB ( + 0.26 ± 0.26 m/s/year vs. + 0.17 ± 0.21 m/s/year ; p = 0.01 ) . After multivariable adjustment , elevated Lp(a ) or OxPL-apoB levels remained independent predictors of faster AS progression . After adjustment for age , sex , and baseline AS severity , patients in the top tertile of Lp(a ) or OxPL-apoB had increased risk of aortic valve replacement and cardiac death . CONCLUSIONS Elevated Lp(a ) and OxPL-apoB levels are associated with faster AS progression and need for aortic valve replacement . These findings support the hypothesis that Lp(a ) mediates AS progression through its associated OxPL and provide a rationale for r and omized trials of Lp(a)-lowering and OxPL-apoB-lowering therapies in AS . ( Aortic Stenosis Progression Observation : Measuring Effects of Rosuvastatin [ ASTRONOMER ] ; NCT00800800 ) |
12,159 | 21,466,578 | Flaws of nursing documentation were identified and the effects of study interventions on its quality . | AIMS This paper reports a review that identified and synthesized nursing documentation audit studies , with a focus on exploring audit approaches , identifying audit instruments and describing the quality status of nursing documentation .
INTRODUCTION Quality nursing documentation promotes effective communication between caregivers , which facilitates continuity and individuality of care . | PURPOSE Evaluate the effectiveness of body mass index ( BMI ) tables placed in exam rooms as an intervention to encourage providers to calculate and record BMI scores in patients ' medical records . DESIGN In a prospect i ve cohort design , medical record data for 276 adult patients at a federally funded community health center in New Engl and were examined from August 2000 to August 2002 following the intervention . METHODS Prominent , multicolored , laminated BMI tables were posted in the exam rooms of one of the study site 's three primary health care teams . Medical record data collected included documentation of BMI calculation in medical records , documentation of an obesity diagnosis , and inclusion of heights and current weights . Frequency distributions were calculated ; chi-square tests were used to identify associations . FINDINGS In contrast to the comparison teams , patients on the intervention team were more likely to have BMI recorded in the medical record . A statistically significant increase in the diagnosis of obesity was observed throughout the health center after the intervention . CONCLUSIONS Posting BMI tables in exam rooms contributed to increased BMI documentation in patients ' medical records Nursing documentation is an important part of clinical documentation . However , documentation of the nursing process is frequently lacking quality . There are high expectations that computer support in nursing documentation will help improve documentation quality . This study aim ed to examine whether the introduction of a computer based nursing documentation system can improve documentation quality . A prospect i ve intervention study was conducted on 4 wards of the University Medical Center Heidelberg over a period of 18 months . Two wards in the Psychiatric University Medical Center Heidelberg were involved in the research study , as well as a dermatological and a pediatric ward . The results of the study show a significant improvement of documentation quantity and quality on three of the four wards . Positive aspects include completeness of documentation on the nursing process , formal aspects and subjective quality improvement by the nurses . Negative aspects were mainly associated with the contents of the care plans The accuracy of patient records in Swedish nursing homes : congruence of record content and nurses ' and patients ' descriptions . Data from patient records will increasingly be used for care planning , quality assessment , research , health planning and allocation of re sources . Knowledge about the accuracy of such secondary data , however , is limited and only a few studies have been conducted on the accuracy of nursing recording . The aim of this study was to analyse the concordance between the nursing documentation in nursing homes and descriptions of some specific problems of nurses and patients . Comparisons were made between wards where nurses had received training in structured recording based on the nursing process ( study group ) and wards where no intervention had taken place ( reference group ) . Data were collected from the patient records of r and omly selected nursing home residents ( n=85 ) . The methods used were audits of patient records and structured interviews with residents and nurses . The study revealed considerable deficiencies in the accuracy of the patient records when the records were compared with the reports from nurses and residents . The overall agreement between the interview data from nurses and from the patient records was low . Concordance was better in the study group as compared with the reference group in which the recorded data were structured only following chronological order . The study unequivocally demonstrates that there are major limitations in using records as a data source for the evaluation , planning and development of care PURPOSE To evaluate the impact of the quality of nursing diagnoses , interventions , and outcomes in an acute care hospital following the implementation of an educational program . METHOD In a pretest-posttest experimental design study , nurses from 12 wards of a Swiss hospital received an educational intervention -- an introductory class and consecutive classes , using a case discussion method --to implement nursing diagnoses , interventions , and outcomes . Two sets of 36 r and omly selected nursing records were evaluated before and after implementation . The quality of documented nursing diagnoses , interventions , and nursing-sensitive patient outcomes was assessed by 29 Likert-type items with a 0 - 4 scale instrument , called Quality of Nursing Diagnoses , Interventions , and Outcomes ( Q-DIO ) and tested using t-tests . FINDINGS Significant enhancements in the quality of documented nursing diagnoses , interventions , and outcomes were found following the implementation of a planned educational program . CONCLUSIONS The implementation of N AND A , NIC , and NOC ( NNN ) nursing diagnoses , interventions , and outcomes led to higher quality of nursing diagnosis documentation , etiology-specific nursing interventions , and nursing-sensitive patient outcomes . IMPLICATION S FOR NURSING PRACTICE Educational measures support nurses to improve documentation of diagnoses , interventions , and outcomes . The Q-DIO is a useful audit tool A two-month r and omized , controlled trial based on 60 patients has been performed on a ward of the Department of Psychiatry at Heidelberg University Medical Center , Germany , to investigate the influence of computer-based nursing documentation on time investment for documentation , quality of documentation and user acceptance . Time measurements , question naires , documentation analysis and interviews were used to compare patients documented with the computer-based system ( PIK group ) with the control group ( patients documented with the paper-based system ) . The results showed the advantages and disadvantages of computer-based nursing documentation . Time needed for nursing care planning was lower in the PIK group . Some formal aspects of quality were considerably better in the PIK group . On the other h and , time required for documentation of tasks and for report writing was greater in the PIK group . User acceptance increased significantly during the study . The interviews indicated a positive influence of PIK on the cooperation between nurses and physicians The purpose of this study undertaken in an acute care hospital was to evaluate sensitivity and specificity of the documentation of nurse-reported delirium symptoms in medical charts . This is a descriptive study based on the clinical assessment s of a study nurse and nursing notes in the medical charts of 226 delirious older patients newly admitted to an acute care hospital . The results of this prospect i ve validation study indicated that documentation of delirium symptoms is poor . Disorientation , agitation and altered level of consciousness were the three symptoms yielding a higher level of sensitivity , but even so said symptoms were reported in less than a third of the medical charts . Univariate analysis suggested that higher comorbidity level , more severe symptoms of delirium and the use of physical restraints were associated with more valid documentation of delirium symptoms in medical charts . Lastly , this study corroborates results of previous studies , indicating that documentation of delirium symptoms in medical charts can be improved . Future study should target improving nurse documentation of delirium symptoms in medical charts The purpose of this study was to determine how use of a st and ardized nomenclature for nursing diagnosis and intervention statements on the computerized nursing care plan in a long-term care ( LTC ) facility would affect patient outcomes , as well as organizational processes and outcomes . An experimental design was used to compare the effects of two methods of documentation : Computer care plan and paper care plan . Twenty participants ( 10 in each group ) were r and omly assigned to either group . No statistically significant differences were found by group for demographic data . Repeated measures ANOVA was computed for each of the study variables with type of care plan , written or computerized , as the independent variable . There were no statistically significant differences between participants , group ( care plan ) , within subjects ( across time ) , or interaction ( group and time ) effects for the dependent variables : Level of care , activities of daily living , perception of pain , cognitive abilities , number of medications , number of bowel medications , number of constipation episodes , weight , percent of meals eaten , and incidence of alteration in skin integrity . There were significantly more nursing interventions and activities on the computerized care plan , although this care plan took longer to develop at each of the three time periods . Results from this study suggest that use of a computerized plan of care increases the number of documented nursing activities and interventions , but further research is warranted to determine if this potential advantage can be translated into improved patient and organizational outcomes in the long-term care setting PURPOSE To describe pilot testing of Quality of Diagnoses , Interventions and Outcomes ( Q-DIO ) , an instrument to measure quality of nursing documentation . DESIGN Instrument testing was performed using a r and om , stratified sample of 60 nursing documentations representing hospital nursing with and without implementation of st and ardized nursing language ( 30 for both strata ) in a Swiss General Acute Hospital . METHODS Internal consistency and intrarater and interrater reliabilities were tested . Through item analyses , the grade s of difficulty and the discrimination validity of items were evaluated . FINDINGS Internal consistency of nursing diagnoses as process produced Cronbach 's alpha .83 ; nursing diagnoses as product .98 ; nursing interventions .90 ; and nursing-sensitive patient outcomes .99 . With Kappas of .95 , the intrarater and interrater reliabilities were good . Criteria for the grade s of difficulty of items and discrimination validity were well met . The results of this study suggest that Q-DIO is a reliable instrument to measure the documentation quality of nursing diagnoses , interventions , and outcomes . Further testing of Q-DIO in other setting s is recommended AIM This paper is a report of a study to investigate the effect of guided clinical reasoning . This method was chosen as a follow-up educational measure ( refresher ) after initial implementation of st and ardized language . BACKGROUND Research has demonstrated nurses ' need for education in diagnostic reasoning to state and document accurate nursing diagnoses , and to choose effective nursing interventions to attain favourable patient outcomes . METHODS In a cluster r and omized controlled experimental study , nurses from three wards received guided clinical reasoning , an interactive learning method . Three wards , receiving classic case discussion s , functioned as control group . Data were collected in 2004 - 2005 . The quality of 225 r and omly selected nursing records , containing 444 documented nursing diagnoses , corresponding interventions and outcomes was evaluated by applying 18 Likert-type items with a 0 - 4 scale of the instrument Quality of Nursing Diagnoses , Interventions and Outcomes . The effect of guided clinical reasoning was tested against classic case discussion s using T-tests and mixed effects model analyses . FINDINGS The mean scores for nursing diagnoses , interventions and outcomes increased significantly in the intervention group . Guided clinical reasoning led to higher quality of nursing diagnosis documentation ; to aetiology-specific interventions and to enhanced nursing-sensitive patient outcomes . In the control group , the quality was unchanged . CONCLUSION Guided clinical reasoning supported nurses ' abilities to state accurate nursing diagnoses , to select effective nursing interventions and to reach and document favourable patient outcomes . The results support the use of the North American Nursing Diagnosis Association , Nursing Interventions Classification and Nursing Outcomes Classification classifications and demonstrate implication s for the electronic nursing documentation The purpose of this analysis was to evaluate documentation of practice provided by a multidisciplinary team of nurses , physicians , and pharmacists who participated in an educational program on postoperative pain management . Chart audit of 787 patient charts at 6 sites revealed documentation of pain histories in approximately 75 % of the charts , most often in the surgeon 's history and physical examination . Examination of multiple assessment items indicated that the experimental group , relative to the control group , experienced an increase of more than 10 % in the documentation of pain intensity , pain quality , pain duration , numeric rating scale used , pain behavior , factors that increase pain , vital signs , sedation level , cognitive status , social interaction , and mood from before the program to 6 months after the program . Across all sites , documentation of assessment , treatment , and treatment outcome data was infrequent and inconsistent . Calculation of documentation of 4 items that constituted a focused assessment of postoperative pain on the surgical floor revealed a significant program effect for assessment of pain quality and pain intensity . A postprogram survey of participants in the educational program revealed an increase in discussion of postoperative pain management with other practitioners and an increase in use of a 0 to 10 scale to rate pain . More documentation of patient pain history , clinical problems , treatment , and follow-up action is needed to improve practice and research AIM AND OBJECTIVES The aim of this paper is to present a study describing nurses ' adherence to the VIPS model by evaluating the quality of nursing assessment , and the quantity of completed nursing care plans . BACKGROUND Numerous efforts have been made over the years to improve nursing documentation in Denmark . Hospitals have traditionally based nurses ' charting on a rudimentary version of the nursing process and on Virginia Henderson 's theory of human needs . In 2002 - 2004 the Copenhagen University Hospital , Rigshospitalet , introduced the Swedish VIPS model for nursing documentation . VIPS is an acronym for well being , integrity , prevention and safety , all of which are seen as major goals for nursing care . The model organizes nursing data according to a system of keywords , which facilitates storage and retrieval of data . DESIGN AND METHODS The design in this part of the study was retrospective , wherein 50 journals from each of the departments of cardiology , neurology , oncology and urology were audited annually for three years using the Cat-ch-Ing instrument ( n=600 ) . All nursing journals were r and omly selected by including the first 50 journals at each site given a specific date . RESULTS The nursing documentation significantly improved during the course of the study . After the second year the participants used the keywords appropriately and correctly according to the VIPS model . Application of primary nursing increased during the study . Initial , ongoing and discharge patient status improved . The nurses ' familiarity with nursing diagnoses , goals and interventions increased . CONCLUSIONS The structured implementation programme significantly improved nursing documentation , and the simultaneous training of the entire nursing staff shows promise . The VIPS model has prepared the nurses for more complex computerized taxonomies and classification systems in the future by improving the nurses ' analytical skills . Relevance to clinical practice . New strategies for improving nursing documentation have been demonstrated AIM The aim was to implement and evaluate a st and ardised nursing record , using patients with leg ulcer as an example , regarding the content of the nursing record and district nurses ' experiences of documentation . METHOD This was a prospect i ve , stratified and r and omised intervention study , with one intervention group and one control group . A st and ardised nursing wound care record was design ed and implemented in the electronic patient record in the intervention group for a period of 3 months . Pre- and post-intervention audits of nursing records [ n=102 and n=92 , respectively ] were carried out and 126 district nurses answered question naires pre-intervention and 83 post-intervention . RESULT The st and ardised nursing wound care record led to more informative , comprehensive and knowledge-intensive documentation according to the audit and district nurses ' opinions . Furthermore , the district nurses ' self-reported knowledge of nursing documentation increased in the intervention group . When the st and ardised nursing wound care record was not used , the documentation was mostly incomplete with a lack of nursing relevance . There were no differences in the district nurses ' experiences of documentation in general between the two groups . CONCLUSION Using the st and ardised nursing wound care record improved nursing documentation meeting legal dem and s , which should increase the safety of patient . There was however a discrepancy between the nurses stated knowledge and how they carried out the documentation . Regular in-service training together with use of evidence based st and ardised nursing records , as a link to clinical reasoning about nursing care , could be ways effecting change PURPOSE To investigate the effects on the quality of nursing diagnostic statements in patient records after education in the nursing process and implementation of new forms for recording . METHODS Quasi-experimental design . R and omly selected patient records review ed before and after intervention from one experimental unit ( n = 70 ) and three control units ( n = 70 ) . A scale with 14 characteristics pertaining to nursing diagnoses was developed and used together with the instrument ( CAT-CH-ING ) for record review . FINDINGS Quality of nursing diagnostic statements improved in the experimental unit , whereas no improvement was found in the control units . Serious flaws in the use of the etiology component were found . CONCLUSION . Nurses must be more concerned with the accuracy and quality of the nursing diagnoses and the etiology component needs to be given special attention . PRACTICE IMPLICATION S Education of RNs in nursing diagnostic statements and peer review using st and ardized evaluation instruments can be means to further enhance RNs ' documentation practice PURPOSE To assess documentation of client data collected at an academic nursing clinic using the Wilson and Cleary Health Related Quality of Life ( HRQOL ) conceptual model as a framework . DATA SOURCES A chart audit of 100 r and omly selected active client records was conducted . CONCLUSIONS Although several significant HRQOL variables were documented , data regarding general health perception and quality of life were not present . The HRQOL conceptual model provided an appropriate structure for evaluating the documentation . Further effort must be made to include key HRQOL dimensions in the clinic 's documentation system . IMPLICATION S FOR PRACTICE Documenting the quality of care provided in nursing clinics is essential in order for other professionals and the public to recognize nursing professionals as accountable and credible . This project formed the basis for a computerized outcomes -based client record system The aims of the study were to investigate , on a daily basis : ( i ) the development and progress of pressure ulcers , ( ii ) the documented nursing interventions for prevention and treatment of pressure ulcers , and ( iii ) when nursing interventions regarding prevention and treatment of pressure ulcers were documented , in relation to patient risk status and the development of pressure ulcers . The study design was prospect i ve , comparative and descriptive . A total of 55 patients with hip fracture were included . To facilitate the nurse 's assessment , a ' pressure ulcer card ' was developed , consisting of the Modified Norton Scale ( MNS ) and descriptions of the four stages of pressure ulcers . The incidence of pressure ulcers was 55 % . The mean rank of the lowest MNS score was significantly lower for patients who developed pressure ulcers than for patients without pressure ulcers . The majority of the pressure ulcers occurred between admission to the ward and the fourth day after surgery . Documented interventions regarding prevention and treatment were : repositioning , overlays , cushions , use of lotion and observation . The mean number of interventions per patient was 2.2 for patients who developed pressure ulcers during their hospital stay . The comprehensiveness and quality of the nursing record was unsatisfactory , and only three nursing records reached the level required by Swedish law . Preventive interventions such as repositioning were documented when the pressure ulcer had already occurred . The lack of nursing documentation regarding prevention and treatment of pressure ulcers may indicate that nurses did not identify pressure ulcers as a prioritized nursing problem for this patient group . The Modified Norton Scale could be a valuable tool for nurses , both identifying the patient at risk and acting as a guide for nursing interventions . The study was approved by the ethics committee of the Faculty of Medicine at Uppsala University |
12,160 | 18,436,889 | Using MRI it has been demonstrated that in patients with acute perfusion diffusion mismatch within 24 hours of stroke onset , acute hyperglycemia correlates with reduced salvage of mismatch tissue from infa rct ion , greater final infa rct size , and worse functional outcome .4 As a consequence , not only has a causal relationship between hyperglycemia and poor outcome been assumed , but also a benefical treatment effect from control of | Marc Fisher MD Kennedy Lees MD Section Editors : Current acute therapies for ischemic stroke are limited .
Only a small proportion of stroke patients are eligible to receive fibrinolytic therapy ; clinical trials of neuroprotectant drugs have yielded disappointing results , and other potential interventions are at very early stages of development .
Against this background , coordinated stroke unit care is , however , of proven benefit ; reduced mortality , institutionalization and dependency .
Clinical trials demonstrating the benefit of stroke unit care have recognized the potential but unproven benefits that may be realized through rigorous physiological monitoring and intervention to correct derangements in the acute phase .
This review will discuss the complex relationship between hyperglycemia and stroke , with particular emphasis on the role of glycemic control in the acute stroke patient . | Summary We investigated the effect of mild hypothermia ( 32–34 ° C ) , mannitol and insulin – induced hypoglycaemia on the ischaemic infa rct volume on permanent middle cerebral artery occlusion with bilateral carotid artery ligation in rats . Temporalis muscle temperature as an indicator of brain temperature was monitored throughout the experiment in all rats , which were r and omly divided into seven groups . During ischaemia , control rats received intravenous saline in a normothermic condition ; treated rats had hypothermia and intravenous saline , hypothermia and mannitol , normothermia and mannitol , normothermia and insulin , normothermia , insulin and glucose , and hypothermia and insulin applied . After the experiment , the animals were killed , and brain sections were stained with haematoxylin and eosin . Images of infa rct areas were determined using a camera attached to the microscope , and analysed by image analysis software . The total volume of infa rct ed tissue , right hemispheric volume , and the percentage of infa rct ion were determined at the end of the image analysis investigation . The infa rct volume on the control group was found to be 128.16±6.67 mm3 . Infa rct volumes in hypothermic groups were significantly smaller than those of the control group ( p<0.05 ) . There were no significant differences between infa rct volumes in the hypothermic groups . However , we found that hypothermia plus mannitol have the greatest neuro-protective effect . In normothermic rats , the infa rct volume decreased proportionally but not statistically ( p>0.05 ) whether mannitol or insulin was given . Our results also demonstrate that pre- , and post-ischaemic serum glucose concentrations influence the volume of infa rct ion . Rats that had had pre-ischaemic high serum glucose concentrations had a higher volume of infa rct than the hypothermic rats ( p<0.05 ) , while rats with post-ischaemic low serum glucose concentrations had a lower volume of infa rct than the control rats BACKGROUND AND PURPOSE Hyperglycemia at the time of ischemic stroke is associated with increased mortality and morbidity . Animal studies suggest that infa rct expansion may be responsible . The influence of persisting hyperglycemia after stroke has not previously been examined . We measured the blood glucose profile after acute ischemic stroke and correlated it with infa rct volume changes using T2- and diffusion-weighted MRI . METHODS We recruited 25 subjects within 24 hours of ischemic stroke symptoms . Continuous glucose monitoring was performed with a glucose monitoring device ( CGMS ) , and 4-hour capillary glucose levels ( BGL ) were measured for 72 hours after admission . MRI and clinical assessment s were performed at acute ( median , 15 hours ) , subacute ( median , 5 days ) , and outcome ( median , 85 days ) time points . RESULTS Mean CGMS glucose and mean BGL glucose correlated with infa rct volume change between acute and subacute diffusion-weighted MRI ( r > or=0.60 , P<0.01 ) , acute and outcome MRI ( r=0.56 , P=0.01 ) , outcome National Institutes of Health Stroke Scale ( NIHSS ; r > or=0.53 , P<0.02 ) , and outcome modified Rankin Scale ( mRS ; r > or=0.53 , P=0.02 ) . Acute and final infa rct volume change and outcome NIHSS and mRS were significantly higher in patients with mean CGMS or mean BGL glucose > or=7 mmol/L. Multiple regression analysis indicated that both mean CGMS and BGL glucose levels > or=7 mmol/L were independently associated with increased final infa rct volume change . CONCLUSIONS Persistent hyperglycemia on serial glucose monitoring is an independent determinant of infa rct expansion and is associated with worse functional outcome . There is an urgent need to study normalization of blood glucose after stroke OBJECTIVES We tested how insulin-glucose infusion followed by multidose insulin treatment in diabetic patients with acute myocardial infa rct ion affected mortality during the subsequent 12 months of follow-up . BACKGROUND Despite significant improvements in acute coronary care , diabetic patients with acute myocardial infa rct ion still have a high mortality rate . METHODS A total of 620 patients were studied : 306 r and omized to treatment with insulin-glucose infusion followed by multidose subcutaneous insulin for > or = 3 months and 314 to conventional therapy . RESULTS The two groups were well matched for baseline characteristics . Blood glucose decreased from 15.4 + /- 4.1 to 9.6 + /- 3.3 mmol/liter ( mean + /- SD ) in the infusion group during the 1st 24 h , and from 15.7 + /- 4.2 to 11.7 + /- 4.1 among control patients ( p < 0.0001 ) . After 1 year 57 subjects ( 18.6 % ) in the infusion group and 82 ( 26.1 % ) in the control group had died ( relative mortality reduction 29 % , p = 0.027 ) . The mortality reduction was particularly evident in patients who had a low cardiovascular risk profile and no previous insulin treatment ( 3-month mortality rate 6.5 % in the infusion group vs. 13.5 % in the control group [ relative reduction 52 % , p = 0.046 ] ; 1-year mortality rate 8.6 % in the infusion group vs. 18.0 % in the control group [ relative reduction 52 % , p = 0.020 ] ) . CONCLUSIONS Insulin-glucose infusion followed by a multidose insulin regimen improved long-term prognosis in diabetic patients with acute myocardial infa rct ion Background —The clinical benefits of insulin previously observed in acute ST-segment – elevation myocardial infa rct ion ( STEMI ) may be partially explained by an anti-inflammatory effect . We assessed this potential effect of insulin in STEMI patients treated with fibrinolytics . Methods and Results —Thirty-two patients receiving reteplase were r and omly assigned infusions of either insulin at 2.5 U/h , dextrose , and potassium ( GIK ) or normal saline and potassium ( C ) for 48 hours . Plasma concentrations of high-sensitivity C-reactive protein ( CRP ) , serum amyloid A ( SAA ) , plasminogen activator inhibitor-1 ( PAI-1 ) , creatine kinase ( CK ) , and CK-MB were measured at baseline and sequentially for 48 hours . Total p47phox protein in mononuclear cells was measured in a subgroup of 13 subjects . Baseline CRP and SAA were significantly increased ( 2- to 4-fold ) at 24 and 48 hours in each group ( P < 0.01 ) . However , in the insulin group , there was a significant ( P < 0.05 ) attenuation of the absolute rise in concentration of CRP and SAA from baseline . The absolute increase of CRP and SAA was reduced by 40 % ( CRP ) and 50 % ( SAA ) at 24 hours and at 48 hours compared with the control group . The absolute increase in PAI-1 from baseline and the percentage increase in p47phox over 48 hours were significantly ( P < 0.05 ) lower in the insulin-treated group . CK-MB peaked earlier and tended to be lower in insulin-treated subjects , especially in patients with inferior MI . Conclusions —Insulin has an anti-inflammatory and profibrinolytic effect in patients with acute MI . These effects may contribute to the clinical benefits of insulin in STEMI Objective : To analyze the frequency , clinical characteristics , and predictors of symptomatic intracerebral hemorrhage ( ICH ) after intraarterial ( IA ) thrombolysis with recombinant pro-urokinase ( r-proUK ) in acute ischemic stroke . Method : The authors conducted an exploratory analysis of symptomatic ICH from a r and omized , controlled clinical trial of IA thrombolysis with r-proUK for patients with angiographically documented occlusion of the middle cerebral artery within 6 hours from stroke onset . Patients ( n = 180 ) were r and omized in a ratio of 2:1 to either 9 mg IA r-proUK over 120 minutes plus IV fixed-dose heparin or IV fixed-dose heparin alone . As opposed to intention to treat , this analysis was based on “ treatment received ” and includes 110 patients given r-proUK and 64 who did not receive any thrombolytic agent . The remaining six patients received out-of- protocol urokinase and were excluded from analysis . The authors analyzed central ly adjudicated ICH with associated neurologic deterioration ( increase in NIH Stroke Scale [ NIHSS ] score of ≥4 points ) within 36 hours of treatment initiation . Results : Symptomatic ICH occurred in 12 of 110 patients ( 10.9 % ) treated with r-proUK and in two of 64 ( 3.1 % ) receiving heparin alone . ICH symptoms in r-proUK – treated patients occurred at a mean of 10.2 ± 7.4 hours after the start of treatment . Mortality after symptomatic ICH was 83 % ( 10/12 patients ) . Only blood glucose was significantly associated with symptomatic ICH in r-proUK – treated patients based on univariate analyses of 24 variables : patients with baseline glucose > 200 mg/dL experienced a 36 % risk of symptomatic ICH compared with 9 % for those with ≤200 mg/dL ( p = 0.022 ; relative risk , 4.2 ; 95 % CI , 1.04 to 11.7 ) . Conclusions : Symptomatic ICH after IA thrombolysis with r-proUK for acute ischemic stroke occurs early after treatment and has high mortality . The risk of symptomatic ICH may be increased in patients with a blood glucose > 200 mg/dL at stroke onset Eleven Type 2 diabetic subjects ( 10 male 1 female : age 56.2 + /- 9.7 ( SD ) yr ) were treated in r and om order either with insulin or with sulphonylureas for 8 weeks each , without attempting to alter glycaemic control between the two treatment periods . Insulin treatment was associated with suppression of endogenous insulin secretion ( fasting C-peptide levels -35.0 + /- 24.2 % ; p = 0.006 ) , and of intact proinsulin ( -43.1 + /- 36.8 % ; p = 0.03 ) and 32,33 split proinsulin -20.1 + /- 27.0 % ; p = 0.03 ) . Activity of plasminogen activator inhibitor ( PAI-1 ) , a fast acting inhibitor of fibrinolysis , decreased significantly ( -14.3 % + /- 27.5 % ; p = 0.02 ) but no changes occurred in concentration of lipoproteins or apoproteins between therapies . Changes in concentrations of 32,33 split and intact proinsulin were closely and significantly related ( rs = 0.83 ; p < 0.001 ) to each other but not with changes in concentrations of C-peptide ( intact proinsulin rs = -0.41 ; p = 0.11 ) and 32,33 split proinsulin rs = -0.27 ; ( p = 0.21 ) . Percentage changes in intact proinsulin concentrations were positively correlated with those in PAI-1 ( rs = 0.51 ; p = 0.05 ) . There was , however a paradoxical negative relationship between changes in C-peptide concentrations and those of PAI-1 ( rs = -0.73 ; p = 0.006 ) . These preliminary observations suggest that insulin treatment in Type 2 diabetic subjects without any changes in glycaemic control is associated with a reduced activity of PAI-1 , but is without effect on any other cardiovascular risk factors . Concentrations of insulin precursor molecules may play a role in determining fibrinolytic activity CONTEXT Glucose-insulin-potassium ( GIK ) infusion is a widely applicable , low-cost therapy that has been postulated to improve mortality in patients with acute ST-segment elevation myocardial infa rct ion ( STEMI ) . Given the potential global importance of GIK infusion , a large , adequately powered r and omized trial is required to determine the effect of GIK on mortality in patients with STEMI . OBJECTIVE To determine the effect of high-dose GIK infusion on mortality in patients with STEMI . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial conducted in 470 centers worldwide among 20,201 patients with STEMI who presented within 12 hours of symptom onset . The mean age of patients was 58.6 years , and evidence -based therapies were commonly used . INTERVENTION Patients were r and omly assigned to receive GIK intravenous infusion for 24 hours plus usual care ( n = 10,091 ) or to receive usual care alone ( controls ; n = 10,110 ) . MAIN OUTCOME MEASURES Mortality , cardiac arrest , cardiogenic shock , and reinfa rct ion at 30 days after r and omization . RESULTS At 30 days , 976 control patients ( 9.7 % ) and 1004 GIK infusion patients ( 10.0 % ) died ( hazard ratio [ HR ] , 1.03 ; 95 % confidence interval [ CI ] , 0.95 - 1.13 ; P = .45 ) . There were no significant differences in the rates of cardiac arrest ( 1.5 % [ 151/10 107 ] in control and 1.4 % [ 139/10,088 ] in GIK infusion ; HR , 0.93 ; 95 % CI , 0.74 - 1.17 ; P = .51 ) , cardiogenic shock ( 6.3 % [ 640/10 107 ] vs 6.6 % [ 667/10 088 ] ; HR , 1.05 ; 95 % CI , 0.94 - 1.17 ; P = .38 ) , or reinfa rct ion ( 2.4 % [ 246/10,107 ] vs 2.3 % [ 236/10,088 ] ; HR , 0.98 ; 95 % CI , 0.82 - 1.17 ; P = .81 ) . The rates of heart failure at 7 days after r and omization were also similar between the groups ( 16.9 % [ 1711/10,107 ] vs 17.1 % [ 1721/10,088 ] ; HR , 1.01 ; 95 % CI , 0.95 - 1.08 ; P = .72 ) . The lack of benefit of GIK infusion on mortality was consistent in prespecified subgroups , including in those with and without diabetes , in those presenting with and without heart failure , in those presenting early and later after symptom onset , and in those receiving and not receiving reperfusion therapy ( thrombolysis or primary percutaneous coronary intervention ) . CONCLUSION In this large , international r and omized trial , high-dose GIK infusion had a neutral effect on mortality , cardiac arrest , and cardiogenic shock in patients with acute STEMI BACKGROUND diabetes mellitus not only increases the risk of ischaemic stroke two- to four-fold but also adversely inXuences prognosis . The prevalence of recognised diabetes mellitus in acute stroke patients is between 8 and 20 % , but between 6 and 42 % of patients may have undiagnosed diabetes mellitus before presentation . Post-stroke hyperglycaemia is frequent and of limited diagnostic value and the oral glucose tolerance test assumes that the patient is clinical ly stable and eating normally . There is a need for a simple and reliable method to predict new diabetes mellitus in acute stroke patients . OBJECTIVES to determine the prevalence of unrecognised diabetes mellitus and impaired glucose tolerance on hospital admission and 12 weeks later in acute stroke patients with post-stroke hyperglycaemia > or = 6.1 mmol/l . To measure the accuracy of hyperglycaemia and elevated glycosylated haemoglobin concentration in predicting the presence of unrecognised diabetes mellitus at 12 weeks . DESIGN acute ( < 24 hours ) stroke patients ( cerebral infa rct ion and primary intracerebral haemorrhage ) with admission hyperglycaemia between 6.0 and 17 mmol/l and without a previous history of insulin-treated diabetes mellitus who were r and omised into the Glucose Insulin in Stroke Trial between October 1997 and May 1999 were studied . The Glucose Insulin in Stroke Trial is a r and omised controlled trial investigating the benefits of maintaining euglycaemia in acute stroke patients with mild to moderate hyperglycaemia . At 12 weeks , survivors underwent a 75 g oral glucose tolerance test . The positive predictive value and negative predictive value of admission plasma glucose > or = 6.1 mmol/l and elevated glycosylated haemoglobin concentration in predicting the presence of diabetes mellitus were used to estimate the prevalence of unrecognised diabetes mellitus in a consecutive series of 582 acute stroke admissions . RESULTS 582 consecutive acute stroke patients were assessed for eligibility for the Glucose Insulin Stroke Trial , of whom 83 ( 14 % ) had recognised diabetes mellitus . One hundred and forty-two patients were r and omised and 62 underwent a 3-month oral glucose tolerance test , of whom 26 ( 42 % ) had normal glucose tolerance , 23 ( 37 % ) had impaired glucose tolerance and 13 ( 21 % ) had diabetes mellitus . Admission plasma glucose > or = 6.1 mmol/l and glycosylated haemoglobin > or = 6.2 % predicted the presence of previously unrecognised diabetes mellitus at 12 weeks with a positive predictive value of 80 % and negative predictive value of 96 % . The estimated prevalence of unrecognised diabetes mellitus in the total series of acute stroke admissions was 16 - 24 % . CONCLUSIONS one-third of all acute stroke patients may have diabetes mellitus . For patients presenting with post-stroke hyperglycaemia , impaired glucose tolerance or diabetes mellitus is present in two-thirds of survivors at 12 weeks . Admission plasma glucose > or = 6.1 mmol/l combined with glycosylated haemoglobin > or = 6.2 % are good predictors of the presence of diabetes mellitus following stroke Intensive insulin therapy ( IIT ) improves the outcome of prolonged critically ill patients , but concerns remain regarding potential harm and the optimal blood glucose level . These questions were addressed using the pooled data set of two r and omized controlled trials . Independent of parenteral glucose load , IIT reduced mortality from 23.6 to 20.4 % in the intention-to-treat group ( n = 2,748 ; P = 0.04 ) and from 37.9 to 30.1 % among long stayers ( n = 1,389 ; P = 0.002 ) , with no difference among short stayers ( 8.9 vs. 10.4 % ; n = 1,359 ; P = 0.4 ) . Compared with blood glucose of 110–150 mg/dl , mortality was higher with blood glucose > 150 mg/dl ( odds ratio 1.38 [ 95 % CI 1.10–1.75 ] ; P = 0.007 ) and lower with < 110 mg/dl ( 0.77 [ 0.61–0.96 ] ; P = 0.02 ) . Only patients with diabetes ( n = 407 ) showed no survival benefit of IIT . Prevention of kidney injury and critical illness polyneuropathy required blood glucose strictly < 110 mg/day , but this level carried the highest risk of hypoglycemia . Within 24 h of hypoglycemia , three patients in the conventional and one in the IIT group died ( P = 0.0004 ) without difference in hospital mortality . No new neurological problems occurred in survivors who experienced hypoglycemia in intensive care units ( ICUs ) . We conclude that IIT reduces mortality of all medical/surgical ICU patients , except those with a prior history of diabetes , and does not cause harm . A blood glucose target < 110 mg/day was most effective but also carried the highest risk of hypoglycemia Animal experiments employing controlled degrees of cerebral ischemia have demonstrated that elevated blood-brain glucose concentrations greatly enhance the extent and degree of subsequent brain damage . The question of whether or not a similar relationship applies in man was examined by retrospectively segregating patients admitted with the diagnosis of ischemic stroke into diabetic ( n = 35 ) and nondiabetic ( n = 72 ) groups . A separate nondiabetic population with ischemic stroke was prospect ively analyzed by dividing patients into those with an admission blood glucose level above ( n = 14 ) or below ( n = 17 ) 120 mg/dl . The neurologic status at discharge was used to stratify outcome as good , fair , or poor in the retrospective study . The ability or inability to return to work was used to separate good and poor outcomes in the prospect i ve study . Neurologic outcome in diabetic patients with stroke was significantly worse ( p less than 0.05 ) than in nondiabetic patients , and the diabetic patients had a greater ( p less than 0.05 ) number of stroke-related deaths . In the prospect i ve study , neurologic outcome also was worse with high blood sugar levels , only 43 percent of the patients with blood glucose values above 120 mg/dl returned to work , whereas 76 percent of those with lower blood sugar values regained employment ( p = 0.061 ) Objective : To study the relation between acute blood glucose level and outcome from ischemic stroke . Background : Hyperglycemia may augment acute ischemic brain injury and increase the risk of hemorrhagic transformation of the infa rct . Methods : The authors analyzed the relation between admission blood glucose level ( within 24 hours from ischemic stroke onset ) and clinical outcome in 1,259 patients enrolled in the Trial of ORG 10172 in Acute Stroke Treatment (TOAST)—a placebo-controlled , r and omized , double-blind trial to test the efficacy of a low-molecular weight heparinoid in acute ischemic stroke . Very favorable outcome was defined as a Glasgow Outcome Scale score of 1 and a modified Barthel index of 19 or 20 . Neurologic improvement at 3 months was defined as a decrease by ≥4 points on the NIH Stroke Scale compared with baseline or a final score of 0 . Hemorrhagic transformation of infa rct was assessed within 10 days after onset of stroke with repeat cerebral CT . Stroke subtype as lacunar or nonlacunar ( atherothromboembolic , cardioembolic , and other or undetermined etiology ) was classified by one investigator after completion of stroke evaluation according to study protocol . Results : In all strokes combined ( p = 0.03 ) and in nonlacunar strokes ( p = 0.02 ) , higher admission blood glucose levels were associated with worse outcome at 3 months according to multivariate logistic regression analysis adjusted for stroke severity , diabetes mellitus , and other vascular risks . In lacunar strokes , the relationship between acute blood glucose level and outcome was related to treatment . In the placebo group , higher admission blood glucose levels were associated with better outcome at 3 months . However , in the active drug group , as the glucose level increased from 50 to 150 mg/dL , the probability of a very favorable outcome decreased sharply and remained relatively unchanged as the glucose level increased further ( p = 0.002 , for overall effect of glucose on outcome ) . Acute blood glucose level was not associated with symptomatic hemorrhagic transformation of infa rcts or with neurologic improvement at 3 months . Conclusions : During acute ischemic stroke hyperglycemia may worsen the clinical outcome in nonlacunar stroke , but not in lacunar stroke , and is not associated with an increased risk of hemorrhagic transformation of the infa rct A primary defect in the vascular action of insulin may be a key intermediate mechanism that links endothelial dysfunction with reduced insulin-mediated cellular glucose uptake in metabolic and cardiovascular disorders . The present study was design ed to characterize more fully the relations between insulin action and endothelial function in male patients with essential hypertension ( H , n=9 ) or type 2 diabetes ( D , n=9 ) along with healthy control subjects ( C ) matched for age , body mass index , and lipid profile . They attended for measurement of whole-body insulin sensitivity ( MCR ) by the hyperinsulinemic clamp technique ( day 1 ) and forearm vasoreactivity in response to intra-arterial infusions of insulin/glucose ( day 2 ) and N(G)-monomethyl-L-arginine ( L-NMMA ) and norepinephrine ( day 3 ) by bilateral venous-occlusion plethysmography . Results expressed as mean+/-SE MCR ( mL/kg per minute ) were 7.22+/-0 . 99 ( C ) , 6.32+/-0.78 ( H ) , and 5.06+/-0.53 ( D ) . Insulin/glucose-mediated vasodilation ( IGMV ) was 17.1+/-5.6 % ( C ) , 17 . 2+/-5.5 % ( H ) , and 12.3+/-6.4 % ( D ) . L-NMMA vasoconstriction ( LNV ) was 37.9+/-5.1 % ( C ) , 37.5+/-2.3 % ( H ) , and 33.6+/-2.8 % ( D ) . There were no significant differences among groups for these parameters . Pooled correlation analyses revealed associations between MCR and IGMV ( r=0 . 46 , P<0.05 ) , MCR and LNV ( r=0.44 , P<0.05 ) , and IGMV and LNV ( r=0.52 , P<0.01 ) . This study supports functional coupling between insulin action ( both metabolic and vascular ) and basal endothelial nitric oxide production in humans Background : Hyperglycaemia on presentation with acute ischaemic stroke ( AIS ) is associated with poor outcome , but intervention is unproven . We investigated the safety and tolerability of one method of glycaemic control . Methods : Patients within 24 h of AIS and plasma glucose 8–20 mmol/l were r and omised to receive either rigorous glycaemic control ( RC ) or st and ard management ( SM ) for 48 h. RC comprised i.v . insulin at a variable rate adjusted for target glucose concentration of 5–8 mmol/l , and intravenous crystalloid . The SM group received intravenous crystalloid alone in an open-label design . Results : Thirteen patients were r and omised to RC and 12 to SM ( age 75 ± 6.2 years ; 40 % male ; 20 % lacunar stroke ; time to treatment 8 ± 6.1 h ; plasma glucose 10.6 ± 0.9 mmol/l ; known diabetes 52 % ; NIHSS 8 , range 2–28 ) . The glucose concentration-time curve was reduced in the RC group ( AUC 324 ± 15 versus 385 ± 28 h·mmol/l , p = 0.04 ) . By 48 h , plasma glucose in both groups was 6.8 ± 1.1 and 7.5 ± 1.3 mmol/l respectively , but mean hourly insulin requirements in the RC group had dropped from 3.25 ± 0.32 units to 1.25 ± 0.5 units ( p < 0.01 ) . One transient episode of hypoglycaemic symptoms occurred in the RC group . Conclusion : Glycaemic control with sliding scale insulin for 48 h is feasible and well-tolerated after AIS . Treatment after 48 h may be unnecessary BACKGROUND Intensive insulin therapy reduces morbidity and mortality in patients in surgical intensive care units ( ICUs ) , but its role in patients in medical ICUs is unknown . METHODS In a prospect i ve , r and omized , controlled study of adult patients admitted to our medical ICU , we studied patients who were considered to need intensive care for at least three days . On admission , patients were r and omly assigned to strict normalization of blood glucose levels ( 80 to 110 mg per deciliter [ 4.4 to 6.1 mmol per liter ] ) with the use of insulin infusion or to conventional therapy ( insulin administered when the blood glucose level exceeded 215 mg per deciliter [ 12 mmol per liter ] , with the infusion tapered when the level fell below 180 mg per deciliter [ 10 mmol per liter ] ) . There was a history of diabetes in 16.9 percent of the patients . RESULTS In the intention-to-treat analysis of 1200 patients , intensive insulin therapy reduced blood glucose levels but did not significantly reduce in-hospital mortality ( 40.0 percent in the conventional-treatment group vs. 37.3 percent in the intensive-treatment group , P=0.33 ) . However , morbidity was significantly reduced by the prevention of newly acquired kidney injury , accelerated weaning from mechanical ventilation , and accelerated discharge from the ICU and the hospital . Although length of stay in the ICU could not be predicted on admission , among 433 patients who stayed in the ICU for less than three days , mortality was greater among those receiving intensive insulin therapy . In contrast , among 767 patients who stayed in the ICU for three or more days , in-hospital mortality in the 386 who received intensive insulin therapy was reduced from 52.5 to 43.0 percent ( P=0.009 ) and morbidity was also reduced . CONCLUSIONS Intensive insulin therapy significantly reduced morbidity but not mortality among all patients in the medical ICU . Although the risk of subsequent death and disease was reduced in patients treated for three or more days , these patients could not be identified before therapy . Further studies are needed to confirm these preliminary data . ( Clinical Trials.gov number , NCT00115479 . Objective : To investigate the effectiveness of maintaining blood glucose levels below 6.1 mmol/L with insulin as prevention of secondary injury to the central and peripheral nervous systems of intensive care patients . Methods : The authors studied the effect of intensive insulin therapy on critical illness polyneuropathy ( CIPNP ) , assessed by weekly EMG screening , and its impact on mechanical ventilation dependency , as a prospect ively planned sub analysis of a large r and omized , controlled trial of 1,548 intensive care patients . In the 63 patients admitted with isolated brain injury , the authors studied the impact of insulin therapy on intracranial pressure , diabetes insipidus , seizures , and long-term rehabilitation at 6 and 12 months follow-up . Results : Intensive insulin therapy reduced ventilation dependency ( p = 0.0007 ; Mantel – Cox log rank test ) and the risk of CIPNP ( p < 0.0001 ) . The risk of CIPNP among the 405 long-stay ( ≥7 days in intensive care unit ) patients was lowered by 49 % ( p < 0.0001 ) . Of all metabolic and clinical effects of insulin therapy , and corrected for known risk factors , the level of glycemic control independently explained this benefit ( OR for CIPNP 1.26 [ 1.09 to 1.46 ] per mmol blood glucose , p = 0.002 ) . In turn , prevention of CIPNP explained the ability of intensive insulin therapy to reduce the risk of prolonged mechanical ventilation ( OR 3.75 [ 1.49 to 9.39 ] , p = 0.005 ) . In isolated brain injury patients , intensive insulin therapy reduced mean ( p = 0.003 ) and maximal ( p < 0.0001 ) intracranial pressure while identical cerebral perfusion pressures were obtained with eightfold less vasopressors ( p = 0.01 ) . Seizures ( p < 0.0001 ) and diabetes insipidus ( p = 0.06 ) occurred less frequently . At 12 months follow-up , more brain-injured survivors in the intensive insulin group were able to care for most of their own needs ( p = 0.05 ) . Conclusions : Preventing even moderate hyperglycemia with insulin during intensive care protected the central and peripheral nervous systems , with clinical consequences such as shortening of intensive care dependency and possibly better long-term rehabilitation Background Recent studies have reported that dexamethasone worsens neuronal injury after brain ischemia . This effect is assumed to be secondary to drug‐induced hyperglycemia . The current study used a rat model to test the hypotheses that insulin treatment of dexamethasone‐induced hyperglycemia would result in a postischemic neurologic outcome that is : ( 1 ) better than that of hyperglycemic , dexamethasone‐treated subjects ; and ( 2 ) better than , or equal to , that of saline‐treated control subjects . Methods Twenty‐four halothane‐anesthetized ( 1.0 % inspired ) rats were r and omly assigned to one of three treatment groups ( N = 8 in each group ) : ( 1 ) normoglycemic , placebo‐treated rats ( group P ) received an intravenous saline infusion ; ( 2 ) hyperglycemic , dexamethasone‐treated rats ( group D ) received 2 mg/kg intraperitoneal dexamethasone at 2 days , 1 day , and 3 h before ischemia plus an intravenous saline infusion ; and ( 3 ) normoglycemic , dexamethasone‐ and insulin‐treated rats ( group DI ) received the same treatment as group D , plus an intravenous insulin infusion shortly before ischemia . Blood gases and acid‐base status were maintained within normal physiologic ranges . Pericranial and rectal temperatures were maintained at normothermia . Forebrain ischemia of 10 min duration was produced using an established model . Neurologic function was assessed by a blinded observer at 24 and 48 h postischemia . Brain histopathology was assessed at the time of ischemia‐related death or after the examination at 48 h. All 24 rats were included in the analysis of neurologic function ; however , only 21 rats that survived for greater or equal to 24 h postischemia were included in the histologic analysis . Results Rats were well matched for systemic physiologic variables , with the exception of glucose concentrations . Plasma glucose concentration immediately before ischemia was as follows : group P = 129+/‐8 mg/dl ( mean+/‐SD ) , group D = 344+/‐29 mg/dl , and group DI = 123+/‐17 mg/dl . At 48 h postischemia , groups P and DI were minimally injured and had similar functional scores . In contrast , all group D rats died of cerebral ischemia . Histologic injury was significantly worse in group D than in either group P or DI , but did not differ significantly between groups P and DI . When all groups were combined , there was a significant correlation between neurologic function and total histopathology score ranks . Conclusions In the current study , dexamethasone administration before brain ischemia result ed in a worsening of postischemic outcome that was related to drug‐induced hyperglycemia . Restoration of normoglycemia , using insulin , result ed in a functional outcome similar to that in group P , and an attenuation of dexamethasone‐associated histologic injury Controversy exists whether acute hyperglycemia is causally associated with worse stroke outcome or simply reflects a more severe stroke . In reversible ischemia models , hyperglycemia is associated with lactic acidosis and conversion of penumbral tissue to infa rct ion . However , the relationship between hyperglycemia , lactic acidosis , and stroke outcome has not been explored in humans . Sixty‐three acute stroke patients were prospect ively evaluated with serial diffusion‐weighted and perfusion‐weighted magnetic resonance imaging and acute blood glucose measurements . Patients with hypoperfused at‐risk tissue were identified by acute perfusion‐diffusion lesion mismatch . As a sub study , acute and subacute magnetic resonance spectroscopy was performed in the 33 most recent patients to assess the relationship between acute blood glucose and lactate production in the ischemic region . In 40 of 63 patients with acute perfusion‐diffusion mismatch , acute hyperglycemia was correlated with reduced salvage of mismatch tissue from infa rct ion , greater final infa rct size , and worse functional outcome . These correlations were independent of baseline stroke severity , lesion size , and diabetic status . Furthermore , higher acute blood glucose in patients with perfusion‐diffusion mismatch was associated with greater acute‐subacute lactate production , which , in turn , was independently associated with reduced salvage of mismatch tissue . In contrast , acute blood glucose levels in nonmismatch patients did not independently correlate with outcome measures , nor was there any acute‐subacute increase in lactate in this group . Acute hyperglycemia increases brain lactate production and facilitates conversion of hypoperfused at‐risk tissue into infa rct ion , which may adversely affect stroke outcome . These findings support the need for r and omized controlled trials of aggressive glycemic control in acute stroke Background Hyperglycemia at the time of acute ischemic stroke has been linked to worse outcome in both human and animal studies . Objective To describe the prevalence and severity of hyperglycemia on hospital admission among acute ischemic stroke patients , to examine the independent relationship of admission hyperglycemia to all-cause mortality , and to document the inpatient management of hyperglycemia . Methods Patients hospitalized with acute ischemic stroke at one hospital from July 1993 to June 1998 ( n = 656 ) were identified . Demographic data , diagnoses , and blood glucose ( BG ) values were retrieved from the electronic medical record system . Admission stroke severity , fingerstick BG results , and new diabetes diagnoses were obtained by chart review . Hyperglycemia was defined as admitting r and om serum BG ≥ 130 mg/dL. Hazard ratios ( HR ) for 30-day , 1-year , and 6-year mortality were calculated using multivariable Cox regression models . Results Hyperglycemia at admission to hospital was present in 40 % of patients with acute stroke . Patients with hyperglycemia were more often women and more likely to have prior diagnoses of diabetes and heart failure . Almost all of these patients remained hyperglycemic during their hospital stay ( mean BG = 206 mg/dL ) , and 43 % received no inpatient hypoglycemic drugs . Hyperglycemic patients had longer hospital stay ( 7 vs 6 days , p = 0.015 ) and higher inpatient hospital charges ( $ 6,611 vs $ 5,262 , p < 0.001 ) . Hyperglycemia independently increased the risk for death at 30 days ( HR 1.87 , p ≤ 0.01 ) , 1 year ( HR 1.75 , p ≤ 0.01 ) , and 6 years after stroke ( HR 1.41 , p ≤ 0.01 ) . Conclusions Admitting hyperglycemia was common among patients with acute ischemic stroke and was associated with increased short- and long-term mortality and with increased inpatient charges . Inpatient blood glucose management was suboptimal in this hospital . A trial of intensive treatment of hyperglycemia should be considered In a prospect i ve study of 109 patients admitted to hospital with a provisional diagnosis of acute stroke , 87 were found to have acute hemiplegic stroke lasting more than 24 hours , and did not have any other co-existing life-threatening disorder . In 81 of these patients , blood glucose and glycosylated haemoglobin ( HbA1 ) were measured at the time of admission . Thirteen of these 81 patients ( 16 % ) were hyperglycaemic -- in 5 cases , normal HbA1 was found in conjunction with hyperglycaemia suggesting that this represented a ' stress ' response . There was no significant difference in age or in blood glucose level between those who died as a result of stroke and those who survived . However , hyperglycaemia with normal HbA1 was demonstrated in 4 of 26 patients who died compared to only one of 55 survivors ( P less than 0.02 ) , and all 3 patients with blood glucose greater than 10 mmol/l in conjunction with normal HbA1 died as a result of stroke . Biochemical evidence of ' stress ' hyperglycaemia in patients with acute stroke suggests a poor prognosis In a prospect i ve study of 86 patients with acute stroke , blood glucose and HbA1 were estimated within 72 h of onset . The prevalence of previously diagnosed diabetes mellitus was 8 % whereas 28 % could be assumed to have had unrecognized hyperglycaemia preceeding the acute event as identified by a stable HbA1 raised more than two SD above the mean reference value . Complete functional recovery of the limbs within 4 weeks of the stroke was confined to those patients with a normal admission blood glucose . None of the patients with a raised admission blood glucose regained full functional recovery within 4 weeks . Cumulative mortality at 4 weeks was significantly raised in patients with an elevated blood glucose value irrespective of their HbA1 values ( p less than 0.05 ) . The prevalence of unrecognized hyperglycaemia as a risk factor for acute stroke is greater than previously reported in the UK and admission blood glucose concentration is of greatest importance in predicting early mortality and morbidity OBJECTIVE To investigate the hypothesis that a submaximal insulin dose reverses the net muscle catabolism associated with severe burns , and to determine its effects on amino acid kinetics . SUMMARY BACKGROUND DATA The authors previously showed that a maximal dose of insulin administered to patients with severe burns promoted skeletal muscle glucose uptake and net protein synthesis . However , this treatment was associated with caloric overload result ing from the large quantities of exogenous glucose required to maintain euglycemia , and hypoglycemia was a potential problem . METHODS Thirteen patients were studied after severe burn injury ( > 60 % total body surface area ) . Patients were r and omly treated by st and ard care ( n = 5 ) or with exogenous insulin ( n = 8) . Data were derived from an arteriovenous model with primed-continuous infusions of stable isotopes and biopsies of the vastus lateralis muscle . RESULTS Net amino acid balance was significantly improved with insulin treatment . Skeletal muscle protein synthesis was significantly greater in the group receiving insulin , whereas muscle protein breakdown was not different between the groups . This submaximal dose of insulin did not affect glucose or amino acid uptake or require a greater caloric intake to avoid hypoglycemia . CONCLUSIONS Submaximal insulin can promote muscle anabolism without eliciting a hypoglycemic response Although hyperglycemia can be a nonspecific response to stress , tight glycemic control during acute myocardial infa rct ion1 and in postoperative ventilated patients 2 has been shown to significantly reduce mortality . Animal3 and human4 - 6 ⇓ ⇓ studies suggest that hyperglycemia also augments acute cerebral ischemia , and clinical efficacy of tight glycemic control during acute cerebral infa rct ion is being investigated.7 Good glycemic control during acute cerebral infa rct ion in nondiabetic patients appears feasible and safe , but this has not been reported in patients with diabetes mellitus.7 Our Institutional Review Board approved this study , and all subjects signed a valid informed consent . We prospect ively administered an IV insulin protocol initiated within 12 hours after onset of cerebral infa rct ion to 24 consecutive patients with admission hyperglycemia ( 9.4 to 22.2 mmol/L or 170 to 400 mg/dL ) . Nurses supervised closely by the principal investigator administered the insulin protocol in an open-label fashion . We modified our insulin protocol after each three to seven treated subjects to improve glycemic control and minimize hypoglycemia while keeping the protocol practical . We adjusted the insulin The aim of the present prospect i ve study was to investigate whether hyperglycemia influences the clinical outcome or the infa rct size after intravenous thrombolysis of focal cerebral ischemia . A consecutive series of hyperglycemic ( n = 14 ) and normoglycemic patients ( n = 17 ) with acute focal cerebral ischemia ( <3 h ) in the middle cerebral artery ( MCA ) territory received rtPA ( 0.9 mg/kg body weight ) intravenously . Clinical outcome was measured using the NIH Stroke Score on admission and was followed up until day 28 . Infa rct volume was measured by diffusion-weighted MR imaging on admission , on days 3 and 7 . There was a significantly better neurological outcome on day 28 in the normoglycemic patients than in the hyperglycemic group ( NIH SS 4.0 versus 7.4 ; p < 0.05 ) . The infa rct ion volume increased significantly in the hyperglycemic patients Δ = 39.9 ± 17.4 % compared to normoglycemic patients Δ = 27.1 ± 14.1 % ( p < 0.05 ) . The present study suggests that hyperglycemia in patients with a focal MCA ischemia can cause a worse clinical outcome despite recanalization of the occluded vessel by thrombolysis therapy . This correlates with a markedly larger increase of the infa rct ion volume in the hyperglycemic group . These results may be explained by an accentuated lactate accumulation and pH decrease by elevated energy levels which can not be compensated by restoration of blood flow alone |
12,161 | 23,897,364 | Improvements in cardiovascular risk profile with largevolume liposuction : A pilot study .
Klein S , Fontana L , Young VL , et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease .
D ’ And rea F , Grella R , Rizzo MR , et al. Changing the metabolic profile by large-volume liposuction : A clinical study conducted with 123 obese women .
Aesthetic Plast Surg .
Giugliano G , Nicoletti G , Grella E , et al. Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women .
Br J Plast Surg .
Swanson E. Photographic measurements in 301 cases of liposuction and abdominoplasty reveal fat reduction without redistribution .
Mohammed BS , Cohen S , Reeds D , Young VL , Klein S. Long-term effects of large-volume liposuction on metabolic risk factors for coronary heart disease .
Rinomhota AS , Bulugahapitiya DU , French SJ , Caddy CM , Griffiths RW , Ross RJ .
Women gain weight and fat mass despite lipectomy at abdominoplasty and breast reduction .
Cintra W , Modolin M , Faintuch J , Gemperli R , Ferreira MC .
C-reactive protein decrease after postbariatric abdominoplasty . | Weight reduction following abdominoplasty : A retrospective case review pilot study .
Sexually dimorphic responses to fat loss after caloric restriction or surgical lipectomy .
Busetto L , Bassetto F , Zocchi M , et al. The effects of the surgical removal of subcutaneous adipose tissue on energy expenditure and adipocytokine concentrations in obese women .
Montoya T , Monereo S , Olivar J , Iglesias P , Díaz P. Effects of orlistat on visceral fat after liposuction .
Benatti F , Solis M , Artioli G , et al. Liposuction induces a compensatory increase of visceral fat which is effectively counteracted by physical activity : A r and omized trial . | OBJECTIVES In animal models , fat removal results in compensatory weight gain . No study has reported measurement of weight following lipectomy in humans . We have examined changes in weight in patients who underwent lipectomy . METHODS In a retrospective analysis , 16 patients who had abdominoplasty and 17 patients who underwent bilateral breast reduction were compared with 16 patients who had carpal tunnel syndrome release . Following this , a prospect i ve study was carried out on 7 subjects awaiting abdominoplasty and 12 subjects awaiting bilateral breast reduction surgery . RESULTS In the retrospective study , all three patient groups gained weight following surgery . The abdominoplasty group was heavier before surgery and showed greatest weight gain but there was no statistically significant difference in weight gain between the groups . In the prospect i ve study , the abdominoplasty group had a mean fat removal of 1.77 kg and breast reduction group had a mean of 3.22 kg . Eighteen months following surgery the abdominoplasty group showed a significant mean increase in body weight ( mean increase : 4.82 kg ) and body mass index ( BMI ) ( mean increase : 1.66 kg/m(2 ) ) . In the bilateral breast reduction group , there was a non-significant mean gain in weight ( mean increase : 0.67 kg ) and BMI ( mean increase : 0.21 kg/m(2 ) ) . CONCLUSIONS Patients undergoing lipectomy during abdominoplasty and bilateral breast reduction will gain weight in the long term . This weight gain probably reflects the expected gain in weight without surgery as a similar finding is observed in patients who have undergone surgery without lipectomy . These results highlight the limitation of lipectomy as a weight control measure Background : There are no published studies of liposuction or abdominoplasty in a large number of patients using measurements of body dimensions . In the absence of rigorous data , some investigators have proposed that fat returns after liposuction . Methods : A prospect i ve study was undertaken among predominantly nonobese consecutive patients undergoing 301 liposuction and abdominoplasty procedures meeting the study criteria ( inclusion rate , 70.7 percent ) . Lower body dimensions were measured using st and ardized photographs taken before and at least 3 months after surgery . Upper body measurements were compared between women who underwent simultaneous cosmetic breast surgery ( n = 67 ) and a group of women who had breast surgery alone ( n = 78 ) to investigate the possibility of fat redistribution . Results : The average weight change was a loss of 2.2 lbs after lower body liposuction ( p < 0.01 ) and 4.6 lbs when combined with abdominoplasty ( p < 0.001 ) . Liposuction significantly reduced abdominal , thigh , knee , and arm width ( p < 0.001 ) . Midabdominal and hip width were more effectively reduced by lipoabdominoplasty than liposuction alone ( p < 0.001 ) . There was no difference in upper body measurements when comparing patients who had simultaneous liposuction and /or abdominoplasty with patients who had cosmetic breast surgery alone . Measurements in patients with at least 1 year of follow-up ( n = 46 ) showed no evidence of fat reaccumulation . Conclusions : Both liposuction and abdominoplasty are valid techniques for long-term fat reduction and improvement of body proportions . There is no evidence of fat regrowth . CLINICAL QUESTION /LEVEL OF EVIDENCE : Therapeutic , III Background Aim ing to clarify the mechanism of weight loss after the restrictive bariatric procedure of sleeve gastrectomy ( LSG ) , the volumes and pressures of the stomach , of the removed part , and of the remaining sleeve were measured in 20 morbidly obese patients . Methods The technique used consisted of occlusion of the pylorus with a laparoscopic clamp and of the gastroesophageal junction with a special orogastric tube connected to a manometer . Instillation of methylene-blue-colored saline via the tube was continued until the intraluminal pressure increased sharply , or the inflated stomach reached 2,000 cc . After recording of measurements , LSG was performed . Results Mean volume of the entire stomach was 1,553 cc ( 600–2,000 cc ) and that of the sleeve 129 cc ( 90–220 cc ) , i.e. , 10 % ( 4–17 % ) and that of the removed stomach was 795 cc ( 400–1,500 cc ) . The mean basal intragastric pressure of the whole stomach after insufflations of the abdominal cavity with CO2 to 15 mmHg was 19 mmHg ( 11–26 mmHg ) ; after occlusion and filling with saline it was 34 mmHg ( 21–45 mmHg ) . In the sleeved stomach , mean basal pressure was similar 18 mmHg ( 6–28 mmHg ) ; when filled with saline , pressure rose to 43 mmHg ( 32–58 mmHg ) . The removed stomach had a mean pressure of 26 mmHg ( 12–47 mmHg ) . There were no postoperative complications and no mortality . Conclusions The notably higher pressure in the sleeve , reflecting its markedly lesser distensibility compared to that of the whole stomach and of the removed fundus , indicates that this may be an important element in the mechanism of weight loss CONTEXT Liposuction is suggested to result in long-term body fat regain that could lead to increased cardiometabolic risk . We hypothesized that physical activity could prevent this effect . OBJECTIVE Our objective was to investigate the effects of liposuction on body fat distribution and cardiometabolic risk factors in women who were either exercise trained or not after surgery . DESIGN , SETTING , AND PARTICIPANTS Thirty-six healthy normal-weight women participated in this 6-month r and omized controlled trial at the University of Sao Paulo , Sao Paulo , Brazil . INTERVENTIONS Patients underwent a small-volume abdominal liposuction . Two months after surgery , the subjects were r and omly allocated into two groups : trained ( TR , n = 18 , 4-month exercise program ) and nontrained ( NT , n = 18 ) . MAIN OUTCOME MEASURES Body fat distribution ( assessed by computed tomography ) was assessed before the intervention ( PRE ) and 2 months ( POST2 ) , and 6 months ( POST6 ) after surgery . Secondary outcome measures included body composition , metabolic parameters and dietary intake , assessed at PRE , POST2 , and POST6 , and total energy expenditure , physical capacity , and sc adipocyte size and lipid metabolism-related gene expression , assessed at PRE and POST6 . RESULTS Liposuction was effective in reducing sc abdominal fat ( PRE vs. POST2 , P = 0.0001 ) . Despite the sustained sc abdominal fat decrement at POST6 ( P = 0.0001 ) , the NT group showed a significant 10 % increase in visceral fat from PRE to POST6 ( P = 0.04 ; effect size = -0.72 ) and decreased energy expenditure ( P = 0.01 ; effect size = 0.95 ) when compared with TR . Dietary intake , adipocyte size , and gene expression were unchanged over time . CONCLUSION Abdominal liposuction does not induce regrowth of fat , but it does trigger a compensatory increase of visceral fat , which is effectively counteracted by physical activity In a prospect i ve study , indices of glucose homeostasis , lipid profile , and systemic inflammation were monitored after an aesthetic abdominoplasty , aim ing to scrutinize the possible metabolic benefits for abdominal fat removal . Premenopausal females with substantial weight loss ( N = 40 ) undergoing circumferential abdominoplasty ( index group , n = 20 ) or augmentation mammoplasty with mastopexy ( controls , n = 20 ) were recruited . All of them originally underwent Roux-en-Y gastric bypass . Variables included BMI , white blood cell count , C-reactive protein , hemoglobin , total cholesterol and fractions , triglycerides , glucose , and HbA1c . Follow-up reached 20.3 ± 13.6 months for index cases and 29.5 ± 17.4 months for controls . The metabolic and inflammatory indices improved after the bariatric surgery . Subsequent monitoring indicated a stable body weight and biochemical profile in both groups . The exceptions were HDL cholesterol and C-reactive protein , which respectively increased and diminished after the abdominoplasty , consistent with an inflammatory and metabolic advantage for this operation . This is the first long-term study in a weight-stable population to point out such a pattern after abdominoplasty OBJECTIVE To analyze the effects of the surgical removal of subcutaneous adipose tissue by ultrasound-assisted megalipoplasty ( UAM ) on energy expenditure and adipocytokine concentrations in obese women . METHODS Fifteen premenopausal obese women with BMI 37.5+/-6.3 kg/m(2 ) ( range : 30.7 - 53.6 kg/m(2 ) ) underwent UAM . Body composition ( by DEXA ) , resting metabolic rate ( REE ) by indirect calorimetry , insulin resistance ( by the HOMA method ) , leptin , C-reactive protein , interleukin-6 , resistin and adiponectin were measured before and 1 , 3 , 28 and 180 days after the procedure . RESULTS UAM significantly reduced fat mass at day 3 , without further changes in the following days . REE increased at day 3 after UAM , returned to baseline levels at day 28 and significantly declined at day 180 . Leptin levels transiently increased after UAM and then declined according to fat mass reduction . C-reactive protein , interleukin-6 and resistin levels acutely increased after UAM and then returned to the baseline levels . Adiponectin levels acutely declined after the procedure and then stabilized to a plasma level slightly lower than at baseline . Insulin resistance deteriorated in the acute post-operative phase and then improved . CONCLUSION The surgical removal of subcutaneous fat was associated to an acute inflammatory reaction with high REE and insulin-resistance . Later on , the metabolic effects of fat mass removal appeared , with a reduction of leptin levels and REE and an improvement of insulin resistance |
12,162 | 19,588,359 | Although positive results were reported for some communities , there was no consistent relationship between being a WHO design ated Safe Community and subsequent changes in observed injury rates .
While the frequency of injury in some study communities did reduce following their design ation as a WHO Safe Community , there remains insufficient evidence from which to draw definitive conclusions regarding the effectiveness of the model . | BACKGROUND The World Health Organization ( WHO ) ' safe communities ' approach to injury prevention has been embraced around the world as a model for co-ordinating community efforts to enhance safety and reduce injury .
Approximately 150 communities throughout the world have formal ' Safe Communities ' design ation .
It is of public health interest to determine to what degree the model is successful , and whether it reduces injury rates .
This Cochrane Review is an up date of a previous published version . | Objective —To evaluate the Latrobe Valley Better Health Injury Prevention Program , a regional community based intervention in south east Victoria , Australia . Method —The evaluation design was quasiexperimental including pre-intervention and post-intervention observations in a predominately town dwelling population of approximately 76 000 . There was no comparison community . Process measures included key informant interviews . Impact evaluation utilised self reported changes in injury risk and protective factors , gathered by a r and om household telephone survey . Outcome evaluation was based on five years of emergency department injury surveillance data for the Latrobe Valley . Results —The program built strategic partnerships , increasing the emphasis on local safety . Activities were implemented in the targeted areas of home , sport , and playground injuries . Some 47 000 educational contacts were made with the community and at least 6000 re source items distributed . There were significant increases in home safety knowledge . Some changes in the areas of playground and sport safety were achieved after partnership development with relevant agencies . Poisson regression models showed significant decreases in the presentation rate for all home injury and for the more severe home injuries . Conclusion —This study clearly demonstrates the difficulty of conducting robust evaluation in the absence of readily available and reliable data and adequate budgets . The Latrobe Valley Better Health Program activities contributed to structural , environmental , and organisational changes that have the potential to reduce injury . The extent of this contribution beyond that made by the statewide injury prevention strategy is not able to be determined In a quasi-experimental study , hospital-treated traffic accident injuries were recorded prospect ively for 7 1/2 years in the two Norwegian cities , Harstad and Trondheim . In Harstad the recorded data were used actively in analysis , planning , and implementation of a community-based injury prevention program . Trondheim was the nonequivalent control city . The intervention was divided into three periods , each of 30 months duration . Preventive efforts were implemented to some extent in period 1 , increasingly in period 2 and period 3 . Traffic safety was promoted in an extensive community program based on the Ottawa charter for health promotion . A 26.6 % overall reduction of traffic injury rates was found in Harstad from period 1 to period 3 ( p < 0.01 ) , whereas a corresponding significant increase was found in the comparison city . Analysis of data from other sources were not conclusive in supporting the Trondheim data as showing the national trend . Alternative explanations for the injury rate reduction in Harstad were assessed by means of other available relevant data . The exact mechanisms that brought about the reduction of injury rates were hard to eluci date because so many intervention elements were implemented at the same time . It is concluded that at least some of the reduction was due to behavioural and structural changes brought about by health promotion . Important factors for the effect of and participation in the prevention program were local relevance and continuous feedback of accident injury data OBJECTIVE --To describe the epidemiology of sports injuries occurring in a community during 8 years and to evaluate the outcome of an intervention implemented against injuries occurring in downhill skiing . METHODS --Hospital treated sports injuries occurring in Harstad , Norway ( population 22 600 ) were recorded prospect ively during an 8 year period . A prevention programme targeting downhill skiing injuries was evaluated . RESULTS --2234 sports injuries accounted for 17.2 % of recorded unintentional injuries . Two out of three injuries occurred in team sports . Soccer accounted for 44.8 % of all sports injuries . Downhill skiing injuries had higher mean score on the abbreviated injury scale than all other sports analysed combined ( P < 0.01 ) . Postintervention injury rates for downhill skiing were reduced by 15 % when adjusting for exposure ( P = 0.24 ) . Further observations are needed for assessing the effectiveness of the downhill skiing safety programme . CONCLUSIONS --Strategies for future sports injury prevention include community involvement , particularly sports organisations . Local data analysis seems to justify some priorities , for example , promotion of helmet use in downhill skiing for young adolescents and prevention of lower limb fractures in male soccer players 15 + years old . Prospect i ve hospital recording of injuries provides a tool for the design and outcome evaluation of sports injury intervention research OBJECTIVE To test the feasibility of a hospital-based injury recording for accident analysis and outcome evaluation of bicyclist and pedestrian injury prevention . DESIGN Prospect i ve injury recording lasting 7 1/2 years , using a quasi-experimental design . SETTING The population of Harstad ( 22,000 ) . INTERVENTION Injury data were evaluated in an injury prevention group and used in planning a community-based intervention . Promotion of bicyclist helmet use and pedestrian safe behaviour was implemented by activating public and voluntary organizations and media . A traffic safety pamphlet containing local traffic injury data was distributed . Changes were made in the physical traffic environment . MAIN OUTCOME MEASURES Injury rates for bicyclists and pedestrians . RESULTS In 275 bicyclists upper extremity and head injuries were predominant 70 % were below 16 years . In 137 pedestrians lower extremity injury was most frequent and children below 10 years had the highest injury rates . Significant injury rate reductions were observed after intervention for child bicyclists and pedestrians . CONCLUSION A hospital-based injury recording is feasible for bicyclists and pedestrian accident analysis , planning injury prevention , and outcome evaluation of the programme . This study indicates that a significant injury rate reduction in children may have been the result of the intervention The objective in this study was to calculate costs and benefits caused by a safe community injury prevention programme in Motala , Sweden . The study design was a quasi-experimental evaluation involving an intervention population and a non-r and om control population . All injuries were recorded before and after an intervention programme . The presented calculations show that costs of injuries in a societal perspective decreased from 116 million Swedish Crowns ( SEK ) to 96 million SEK , while the cost for the intervention was estimated at approximately 10 million SEK . Thus , the safe community injury prevention programme in Motala should be judged as cost-effective BACKGROUND Although social ine quality in health has been an argument for community-based injury prevention programmes , intervention outcomes with regard to differences in social st and ing have not been analysed . The objective of this study was to investigate rates of injuries treated in health-care among members of households at different levels of labour market integration before and after the implementation of a WHO Safe Community programme . METHODS A quasi-experimental design was used with pre- and post-implementation data collection covering the total population s < 65 years of age during one year in the programme implementation municipality ( population 41 000 ) and in a control municipality ( population 26 000 ) . Changes in injury rates were studied using prospect i ve registration of all acute care episodes with regard to social st and ing in both areas during the study periods . RESULTS Male members of households categorized as not vocationally active displayed the highest pre-intervention injury rates . Also after the intervention , males in households classified as not vocationally active displayed notably elevated injury rates in both the control and study areas . Households in the study area in which the significant member was employed showed a post-intervention decrease in injury rate among both men ( P < 0.001 ) and women ( P < 0.01 ) . No statistically significant change was observed in households in which the significant member was self-employed or not vocationally active . In the control area , only an aggregate-level decrease ( P < 0.05 ) among members of households in which the significant member was employed was observed . CONCLUSIONS The study displayed areas for improvement in the civic network-based WHO Safe Community model . Even though members of non-vocationally active households , in particular men , were at higher pre-intervention injury risk , they were not affected by the interventions . This fact has to be addressed when planning future community-based injury prevention programmes STUDY OBJECTIVE : To describe a community based programme to prevent fractures result ing from falls and evaluate the outcome in terms of changes in fracture rates and short term hospital care costs . DESIGN : Prospect i ve intervention study . SETTING : The Norwegian municipalities of Harstad ( intervention ) and Trondheim ( reference ) from 1 July 1985 to 30 June 1993 . PARTICIPANTS : The person-years of the study were estimated from yearly census data on people aged 65 years and over . There were 22970 person years in Harstad and 158911 in Trondheim . MEASUREMENTS AND MAIN RESULTS : The variables were selected and coded according to the Nordic system and the data were collected as part of a national injury surveillance system . The first three years of the study provided baseline data , while the last five years involved community based interventions -eg , the removal of environmental hazards in homes and promotion of the use of safe footwear outdoors in winter . Rates of fracture from falls did not decline in nursing homes but decreased 26.3 % in private homes ( p < 0.01 ) . In 65 - 79 year olds , there was a 48.7 % reduction in fall-fracture rates for men in traffic areas in winter ( p < 0.05 ) . The data from the reference city , Trondheim , suggested a significant rise in fractures caused by falls . There was a 16.7 % reduction in hospital admission rates of fall-fracture patients from private homes , indicating a substantial saving in short term hospital costs . The observed fall-fracture rate reductions in private homes and traffic areas suggest that major parts of the interventions were effective . CONCLUSION : Fall-fracture prophylaxis in the aged is possible in a community based setting that utilises high quality , local injury data STUDY OBJECTIVE To do a complete survey of hospital-treated fractures in the aged ( 65 + years old ) and to report the characteristics and distribution of all fractures occurring within this defined population . DESIGN Prospect i ve injury recording study . SETTING The Norwegian municipality of Harstad ( population 23,000 ) during eight years from 1 July 1985 . PARTICIPANTS The person years of the study estimated from yearly census data , were 22,970 . MEASUREMENTS AND MAIN RESULTS The variables were selected and coded according to the Nordic system and the data were collected as part of a national injury surveillance system . Of 753 recorded fractures , nine out of ten were caused by falls . 50.6 % of fractures occurred in private homes , 24.4 % in traffic areas ( traffic accidents excluded ) , 13.3 % in nursing homes . Adjusting for exposure , fracture rates ( per 1000 person years ) were 70.0 in nursing homes , 17.7 in private homes , and 8.5 in traffic areas in winter ( traffic accidents excluded ) . The fracture risk in traffic areas increased fivefold in months with snow . CONCLUSION Nine out of ten fractures in the aged were caused by falls . Although the fracture risk for the elderly living in a nursing home was four times as high as those living in private homes , the volume of fractures occurring in private homes and traffic areas make them a prime target for interventions . Continuous prospect i ve hospital recording of fractures in a community of aged is feasible and provides a tool for targeting interventions and evaluating the outcome of a community fall-fracture prevention programme Objective —To evaluate a community based programme for evidence based prevention of injuries during physical exercise . Design —Quasi-experimental evaluation using an intervention population and a non-r and om control population . Participants — Study municipality ( population 41 000 ) and control municipality ( population 26 000 ) in Sweden . Main outcome measures —Morbidity rate for sports related injuries treated in the health care system ; severity classification according to the abbreviated injury scale ( AIS ) . Results —The total morbidity rate for sports related injuries in the study area decreased by 14 % from 21 to 18 injuries per 1000 population years ( odds ratio 0.87 ; 95 % confidence interval ( CI ) 0.79 to 0.96 ) . No tendency towards a decrease was observed in people over 40 . The rate of moderately severe injury ( AIS 2 ) decreased to almost half ( odds ratio 0.58 ; 95 % CI 0.50 to 0.68 ) , whereas the rate of minor injuries ( AIS 1 ) increased ( odds ratio 1.22 ; 95 % CI 1.06 to 1.40 ) . The risk of severe injuries ( AIS 3–6 ) remained constant . The rate of total sports injury in the control area did not change ( odds ratio 0.93 ; 95 % CI 0.81 to 1.07 ) , and the trends in the study and control areas were not statistically significantly different . Conclusion —An evidence based prevention programme based on local safety rules and educational programmes can reduce the burden of injuries related to physical exercise in a community . Future studies need to look at adjusting the programme to benefit all age groups Preventing children 's thermal injuries requires changes to both the home environment and the behaviour of family members . Two pilot studies were undertaken of a school-based programme that taught children aged 7 - 11 years about burns and scalds hazards , and encouraged changes to the home environment and family practice s through a take-home exercise . Both studies took place at ethnically diverse schools from low/middle-income areas of Waitakere City , New Zeal and . Study 1 involved 55 children who received the programme , and Study 2 involved 64 children who received the programme and 71 children from a control school . The children 's ability to identify the burns and scalds hazards illustrated in a series of pictures was measured before and after the programme . Children who received the programme showed considerable improvement in hazard identification at the post-test , while children at the control school showed minimal improvement . The take-home exercise was completed by 85 % of the children and their families in Study 1 , and 61 % of the participants from the intervention school in Study 2 . In both studies families reported positive safety changes as a result of the programme . The programme appeared equally effective with all the ethnic groups involved . Future development of the programme is discussed |
12,163 | 28,521,798 | Overall , RDTs were performed safely and effectively by community health workers provided they receive proper training .
Analogous information was largely absent for formal health care workers .
Tests were generally accurate across context s , except for in drug shops where lower specificities were observed .
Conclusions Malaria RDTs are generally used well , though compliance with test results is variable – especially in the formal health care sector . | Background The World Health Organization recommends parasitological confirmation of malaria prior to treatment .
Malaria rapid diagnostic tests ( RDTs ) represent one diagnostic method that is used in a variety of context s to overcome limitations of other diagnostic techniques .
Malaria RDTs increase the availability and feasibility of accurate diagnosis and may result in improved quality of care .
Though RDTs are used in a variety of context s , no studies have compared how well or effectively RDTs are used across these context s. This review assesses the diagnostic use of RDTs in four different context s : health facilities , the community , drug shops and schools .
If low adherence rates are extrapolated , thous and s of patients may be incorrectly diagnosed and receive inappropriate treatment result ing in a low quality of care and unnecessary drug use . | OBJECTIVE To examine the extent to which district health teams could reduce the burden of malaria , a continuing major cause of mortality and morbidity , in a situation where severe re source constraints existed and integrated care was provided . METHODS Antimalarial drugs were prepackaged into unit doses in an attempt to improve compliance with full courses of chemotherapy . FINDINGS Compliance improved by approximately 20 % in both adults and children . There were 50 % reductions in cost to patients , waiting time at dispensaries and drug wastage at facilities . The intervention , which tended to improve both case and drug management at facilities , was well accepted by health staff and did not involve them in additional working time . CONCLUSION The prepackaging of antimalarials at the district level offers the prospect of improved compliance and a reduction in the spread of resistance Abstract Objective To compare the impact of malaria rapid diagnostic tests ( mRDTs ) , used by community health workers ( CHWs ) , on the proportion of children < 5 years of age receiving appropriately targeted treatment with artemisinin‐based combination therapy ( ACT ) , vs. presumptive treatment . Methods Cluster‐r and omized trials were conducted in two contrasting areas of moderate‐to‐high and low malaria transmission in rural Ug and a. Each trial examined the effectiveness of mRDTs in the management of malaria and targeting of ACTs by CHWs comparing two diagnostic approaches : ( i ) presumptive clinical diagnosis of malaria [ control arm ] and ( ii ) confirmatory diagnosis with mRDTs followed by ACT treatment for positive patients [ intervention arm ] , with village as the unit of r and omisation . Treatment decisions by CHWs were vali date d by microscopy on a reference blood slide collected at the time of consultation , to compare the proportion of children < 5 years receiving appropriately targeted ACT treatment , defined as patients with microscopically‐confirmed presence of parasites in a peripheral blood smear receiving artemether‐lumefantrine or rectal artesunate , and patients with no malaria parasites not given ACT . Results In the moderate‐to‐high transmission area , ACT treatment was appropriately targeted in 79.3 % ( 520/656 ) of children seen by CHWs using mRDTs to diagnose malaria , vs. 30.8 % ( 215/699 ) of children seen by CHWs using presumptive diagnosis ( P < 0.001 ) . In the low transmission area , 90.1 % ( 363/403 ) children seen by CHWs using mRDTs received appropriately targeted ACT treatment vs. 7.8 % ( 64/817 ) seen by CHWs using presumptive diagnosis ( P < 0.001 ) . Low mRDT sensitivity in children with low‐density parasitaemia ( < 200 parasites/μl ) was identified as a potential concern . Conclusion When equipped with mRDTs , ACT treatments delivered by CHWs are more accurately targeted to children with malaria parasites . mRDT use could play an important role in reducing overdiagnosis of malaria and improving fever case management within iCCM , in both moderate‐to‐high and low transmission areas . Nonetheless , missed treatments due to the low sensitivity of current mRDTs in patients with low parasite density are a concern . For community‐based treatment in areas of low transmission and /or non‐immune population s , presumptive treatment of all fevers as malaria may be advisable , until more sensitive diagnostic assays , suitable for routine use by CHWs in remote setting s , become available Background It is important that community-based health insurance ( CBHI ) schemes are design ed in such a way as to ensure the relevance of the benefit packages to potential clients . Hence , this paper provides an underst and ing of the preferred benefit packages by different economic status groups as well as urban and rural dwellers for CBHI in Southeast Nigeria . Methods The study took place in rural , urban and semi-urban communities of south-east Nigeria . A question naire was used to collect information from 3070 r and omly picked household heads . Focus group discussion s were used to collect qualitative data . Data was examined for links between preferences for benefit packages with SES and geographic residence of the respondents . Results Respondents in the rural areas and in the lower SES preferred a comprehensive benefit package which includes all inpatient , outpatient and emergencies services , while those in urban areas as well as those in the higher SES group showed a preference for benefit packages which will cover only basic disease control interventions . Conclusion Equity concerns in preferences for services to be offered by the CBHI scheme should be addressed for CBHI to succeed in different context Background The increasing investment in malaria rapid diagnostic tests ( RDTs ) to differentiate malarial and non-malarial fevers , and an awareness of the need to improve case management of non-malarial fever , indicates an urgent need for high quality evidence on how best to improve prescribers ’ practice s. Methods A three-arm stratified cluster-r and omised trial was conducted in 36 primary healthcare facilities from September 2010 to March 2012 within two rural districts in northeast Tanzania where malaria transmission has been declining . Interventions were guided by formative mixed- methods research and were introduced in phases . Prescribing staff from all facilities received st and ard Ministry of Health RDT training . Prescribers from facilities in the health worker ( HW ) and health worker-patient ( HWP ) arms further participated in small interactive peer-group training sessions with the HWP additionally receiving clinic posters and patient leaflets . Performance feedback and motivational mobile-phone text messaging ( SMS ) were added to the HW and HWP arms in later phases . The primary outcome was the proportion of patients with a non-severe , non-malarial illness incorrectly prescribed a ( recommended ) antimalarial . Secondary outcomes investigated RDT uptake , adherence to results , and antibiotic prescribing . Results St and ard RDT training reduced pre-trial levels of antimalarial prescribing , which was sustained throughout the trial . Both interventions significantly lowered incorrect prescribing of recommended antimalarials from 8 % ( 749/8,942 ) in the st and ard training arm to 2 % ( 250/10,118 ) in the HW arm ( adjusted RD ( aRD ) 4 % ; 95 % confidence interval ( CI ) 1 % to 6 % ; P = 0.008 ) and 2 % ( 184/10,163 ) in the HWP arm ( aRD 4 % ; 95 % CI 1 % to 6 % ; P = 0.005 ) . Small group training and SMS were incrementally effective . There was also a significant reduction in the prescribing of antimalarials to RDT-negatives but no effect on RDT-positives receiving an ACT . Antibiotic prescribing was significantly lower in the HWP arm but had increased in all arms compared with pre-trial levels . Conclusions Small group training with SMS was associated with an incremental and sustained improvement in prescriber adherence to RDT results and reducing over-prescribing of antimalarials to close to zero . These interventions may become increasingly important to cope with the wider range of diagnostic and treatment options for patients with acute febrile illness in Africa . Trial registration Clinical Trials.gov ( # NCT01292707 ) 29 January 2011 Background Malaria is a major cause of paediatric morbidity and mortality . As no clinical features clearly differentiate malaria from other febrile illnesses , and malaria diagnosis is challenged by often lacking laboratory equipment and expertise , overdiagnosis and overtreatment is common . Methods Children admitted with fever at the general paediatric wards at Muhimbili National Hospital ( MNH ) , Dar es Salaam , Tanzania from January to June 2009 were recruited consecutively and prospect ively . Demographic and clinical features were registered . Routine thick blood smear microscopy at MNH was compared to results of subsequent thin blood smear microscopy , and rapid diagnostics tests ( RDTs ) . Genus-specific PCR of Plasmodium mitochondrial DNA was performed on DNA extracted from whole blood and species-specific PCR was done on positive sample s. Results Among 304 included children , 62.6 % had received anti-malarials during the last four weeks prior to admission and 65.1 % during the hospital stay . Routine thick blood smears , research blood smears , PCR and RDT detected malaria in 13.2 % , 6.6 % , 25.0 % and 13.5 % , respectively . Positive routine microscopy was confirmed in only 43 % ( 17/40 ) , 45 % ( 18/40 ) and 53 % ( 21/40 ) , by research microscopy , RDTs and PCR , respectively . Eighteen percent ( 56/304 ) had positive PCR but negative research microscopy . Reported low parasitaemia on routine microscopy was associated with negative research blood slide and PCR . RDT-positive cases were associated with signs of severe malaria . Palmar pallor , low haemoglobin and low platelet count were significantly associated with positive PCR , research microscopy and RDT . Conclusions The true morbidity attributable to malaria in the study population remains uncertain due to the discrepancies in results among the diagnostic methods . The current routine microscopy appears to result in overdiagnosis of malaria and , consequently , overuse of anti-malarials . Conversely , children with a false positive malaria diagnosis may die because they do not receive treatment for the true cause of their illness . RDTs appear to have the potential to improve routine diagnostics , but the clinical implication of the many RDT-negative , PCR-positive sample s needs to be eluci date Background Artemisinin-based combination therapy ( ACT ) is the first-line malaria treatment throughout most of the malaria-endemic world . Data on ACT availability , price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality -assured ACT supply . This paper presents supply side data from ACTwatch outlet surveys in Benin , the Democratic Republic of Congo ( DRC ) , Madagascar , Nigeria , Ug and a and Zambia . Methods Between March 2009 and June 2010 , nationally representative surveys of outlets providing anti-malarials to consumers were conducted . A census of all outlets with the potential to provide anti-malarials was conducted in clusters sample d r and omly . Results 28,263 outlets were censused , 51,158 anti-malarials were audited , and 9,118 providers interviewed . The proportion of public health facilities with at least one first-line quality -assured ACT in stock ranged between 43 % and 85 % . Among private sector outlets stocking at least one anti-malarial , non-artemisinin therapies , such as chloroquine and sulphadoxine-pyrimethamine , were widely available ( > 95 % of outlets ) as compared to first-line quality -assured ACT ( < 25 % ) . In the public/not-for-profit sector , first-line quality -assured ACT was available for free in all countries except Benin and the DRC ( US$ 1.29 [ Inter Quartile Range ( IQR ) : $ 1.29-$1.29 ] and $ 0.52[IQR : $ 0.00-$1.29 ] per adult equivalent dose respectively ) . In the private sector , first-line quality -assured ACT was 5 - 24 times more expensive than non-artemisinin therapies . The exception was Madagascar where , due to national social marketing of subsidized ACT , the price of first-line quality -assured ACT ( $ 0.14 [ IQR : $ 0.10 , $ 0.57 ] ) was significantly lower than the most popular treatment ( chloroquine , $ 0.36 [ IQR : $ 0.36 , $ 0.36 ] ) . Quality -assured ACT accounted for less than 25 % of total anti-malarial volumes ; private-sector quality -assured ACT volumes represented less than 6 % of the total market share . Most anti-malarials were distributed through the private sector , but often comprised non-artemisinin therapies , and in the DRC and Nigeria , oral artemisinin monotherapies . Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector . Conclusions These st and ardized , nationally representative results demonstrate the typically low availability , low market share and high prices of ACT , in the private sector where most anti-malarials are accessed , with some exceptions . The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries . The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria Background Early diagnosis and prompt , effective treatment of uncomplicated malaria is critical to prevent severe disease , death and malaria transmission . We assessed the impact of rapid malaria diagnostic tests ( RDTs ) by community health workers ( CHWs ) on provision of artemisinin-based combination therapy ( ACT ) and health outcome in fever patients . Methodology /Principal Findings Twenty-two CHWs from five villages in Kibaha District , a high-malaria transmission area in Coast Region , Tanzania , were trained to manage uncomplicated malaria using RDT aided diagnosis or clinical diagnosis ( CD ) only . Each CHW was r and omly assigned to use either RDT or CD the first week and thereafter alternating weekly . Primary outcome was provision of ACT and main secondary outcomes were referral rates and health status by days 3 and 7 . The CHWs enrolled 2930 fever patients during five months of whom 1988 ( 67.8 % ) presented within 24 hours of fever onset . ACT was provided to 775 of 1457 ( 53.2 % ) patients during RDT weeks and to 1422 of 1473 ( 96.5 % ) patients during CD weeks ( Odds Ratio ( OR ) 0.039 , 95 % CI 0.029–0.053 ) . The CHWs adhered to the RDT results in 1411 of 1457 ( 96.8 % , 95 % CI 95.8–97.6 ) patients . More patients were referred on inclusion day during RDT weeks ( 10.0 % ) compared to CD weeks ( 1.6 % ) . Referral during days 1–7 and perceived non-recovery on days 3 and 7 were also more common after RDT aided diagnosis . However , no fatal or severe malaria occurred among 682 patients in the RDT group who were not treated with ACT , supporting the safety of withholding ACT to RDT negative patients . Conclusions / Significance RDTs in the h and s of CHWs may safely improve early and well-targeted ACT treatment in malaria patients at community level in Africa . Trial registration Clinical Trials.gov Abstract Objective To evaluate the impact – on diagnosis and treatment of malaria – of introducing rapid diagnostic tests to drug shops in eastern Ug and a. Methods Overall , 2193 households in 79 study villages with at least one licensed drug shop were enrolled and monitored for 12 months . After 3 months of monitoring , drug shop vendors in 67 villages r and omly selected for the intervention were offered training in the use of malaria rapid diagnostic tests and – if trained – offered access to such tests at a subsidized price . The remaining 12 study villages served as controls . A difference-in-differences regression model was used to estimate the impact of the intervention . Findings Vendors from 92 drug shops successfully completed training and 50 actively stocked and performed the rapid tests . Over 9 months , trained vendors did an average of 146 tests per shop . Households reported 22 697 episodes of febrile illness . The availability of rapid tests at local drug shops significantly increased the probability of any febrile illness being tested for malaria by 23.15 % ( P = 0.015 ) and being treated with an antimalarial drug by 8.84 % ( P = 0.056 ) . The probability that artemisinin combination therapy was bought increased by a statistically insignificant 5.48 % ( P = 0.574 ) . Conclusion In our study area , testing for malaria was increased by training drug shop vendors in the use of rapid tests and providing them access to such tests at a subsidized price . Additional interventions may be needed to achieve a higher coverage of testing and a higher rate of appropriate responses to test results Background Since drug shops play an important role in treatment of fever , introducing rapid diagnostic tests ( RDTs ) for malaria at drug shops may have the potential of targeting anti-malarial drugs to those with malaria parasites and improve rational drug use . As part of a cluster r and omized trial to examine impact on appropriate treatment of malaria in drug shops in Ug and a and adherence to current malaria treatment policy guidelines , a survey was conducted to estimate baseline prevalence of , and factors associated with , appropriate treatment of malaria to enable effective design and implementation of the cluster r and omized trial . Methods A survey was conducted within 20 geographical clusters of drug shops from May to September 2010 in Mukono district , central Ug and a. A cluster was defined as a parish representing a cluster of drug shops . Data was collected using two structured question naires : a provider question naire to capture data on drug shops ( n=65 ) including provider characteristics , knowledge on treatment of malaria , previous training received , type of drugs stocked , reported drug sales , and record keeping practice s ; and a patient question naire to capture data from febrile patients ( n=540 ) exiting drug shops on presenting symptoms , the consultation process , treatment received , and malaria diagnoses . Malaria diagnosis made by drug shop vendors were confirmed by the study team through microscopy examination of a blood slide to ascertain whether appropriate treatment was received . Results Among febrile patients seen at drug shops , 35 % had a positive RDT result and 27 % had a positive blood slide . Many patients ( 55 % ) had previously sought care from another drug shop prior to this consultation . Three quarters ( 73 % ) of all febrile patients seen at drug shops received an anti-malarial , of whom 39 % received an ACT and 33 % received quinine . The rest received another non-artemisinin monotherapy . Only one third ( 32 % ) of patients with a positive blood slide had received treatment with Coartem ® while 34 % of those with a negative blood slide had not received an anti-malarial . Overall appropriate treatment was 34 ( 95 % CI : 28 – 40 ) with substantial between-cluster variation , ranging from 1 % to 55 % . Conclusion In this setting , the proportion of malaria patients receiving appropriate ACT treatment at drug shops was low . This was due to the practice of presumptive treatment , inadequate training on malaria management and lack of knowledge that Coartem ® was the recommended first-line treatment for malaria . There is urgent need for interventions to improve treatment of malaria at these outlets Objective To compare rapid diagnostic tests ( RDTs ) for malaria with routine microscopy in guiding treatment decisions for febrile patients . Design R and omised trial . Setting Outpatient departments in northeast Tanzania at varying levels of malaria transmission . Participants 2416 patients for whom a malaria test was requested . Intervention Staff received training on rapid diagnostic tests ; patients sent for malaria tests were r and omised to rapid diagnostic test or routine microscopy Main outcome measure Proportion of patients with a negative test prescribed an antimalarial drug . Results Of 7589 outpatient consultations , 2425 ( 32 % ) had a malaria test requested . Of 1204 patients r and omised to microscopy , 1030 ( 86 % ) tested negative for malaria ; 523 ( 51 % ) of these were treated with an antimalarial drug . Of 1193 patients r and omised to rapid diagnostic test , 1005 ( 84 % ) tested negative ; 540 ( 54 % ) of these were treated for malaria ( odds ratio 1.13 , 95 % confidence interval 0.95 to 1.34 ; P=0.18 ) . Children aged under 5 with negative rapid diagnostic tests were more likely to be prescribed an antimalarial drug than were those with negative slides ( P=0.003 ) . Patients with a negative test by any method were more likely to be prescribed an antibiotic ( odds ratio 6.42 , 4.72 to 8.75 ; P<0.001 ) . More than 90 % of prescriptions for antimalarial drugs in low-moderate transmission setting s were for patients for whom a test requested by a clinician was negative for malaria . Conclusions Although many cases of malaria are missed outside the formal sector , within it malaria is massively over-diagnosed . This threatens the sustainability of deployment of artemisinin combination treatment , and treatable bacterial diseases are likely to be missed . Use of rapid diagnostic tests , with basic training for clinical staff , did not in itself lead to any reduction in over-treatment for malaria . Interventions to improve clinicians ' management of febrile illness are essential but will not be easy . Trial registration Clinical trials NCT00146796 Abstract Objective To study the diagnosis and outcomes in people admitted to hospital with a diagnosis of severe malaria in areas with differing intensities of malaria transmission . Design Prospect i ve observational study of children and adults over the course a year . Setting 10 hospitals in north east Tanzania . Participants 17 313 patients were admitted to hospital ; of these 4474 ( 2851 children aged under 5 years ) fulfilled criteria for severe disease . Main outcome measure Details of the treatment given and outcome . Altitudes of residence ( a proxy for transmission intensity ) measured with a global positioning system . Results Blood film microscopy showed that 2062 ( 46.1 % ) of people treated for malaria had Plasmodium falciparum ( slide positive ) . The proportion of slide positive cases fell with increasing age and increasing altitude of residence . Among 1086 patients aged ≥ 5 years who lived above 600 metres , only 338 ( 31.1 % ) were slide positive , while in children < 5 years living in areas of intense transmission ( < 600 metres ) most ( 958/1392 , 68.8 % ) were slide positive . Among 2375 people who were slide negative , 1571 ( 66.1 % ) were not treated with antibiotics and of those , 120 ( 7.6 % ) died . The case fatality in slide negative patients was higher ( 292/2412 , 12.1 % ) than for slide positive patients ( 142/2062 , 6.9 % ) ( P < 0.001 ) . Respiratory distress and altered consciousness were the strongest predictors of mortality in slide positive and slide negative patients and in adults as well as children . Conclusions In Tanzania , malaria is commonly overdiagnosed in people presenting with severe febrile illness , especially in those living in areas with low to moderate transmission and in adults . This is associated with a failure to treat alternative causes of severe infection . Diagnosis needs to be improved and syndromic treatment considered . Routine hospital data may overestimate mortality from malaria by over twofold Background In Ug and a , parasite-based diagnosis is recommended for every patient suspected to have malaria before prescribing anti-malarials . However , the majority of patients are still treated presumptively especially in low-level health units . The feasibility of implementing parasite-based diagnosis for uncomplicated malaria in rural health centres ( HCs ) was investigated with a view to recommending measures for scaling up the policy . Methods Thirty HCs were r and omized to implement parasite-based diagnosis based on rapid diagnostic tests [ RDTs ] ( n = 10 ) , blood microscopy ( n = 10 ) and presumptive diagnosis ( control arm ) ( n = 10 ) . Feasibility was assessed by comparing the proportion of patients who received parasite-based diagnosis ; with a positive malaria parasite-based diagnosis who received artemether-lumefantrine ( AL ) ; with a negative malaria parasite-based diagnosis who received AL ; and patient waiting time . Clinical trials.gov : NCT00565071 . Results 102 , 087 out patients were enrolled . Patients were more likely to be tested in the RDT 44 , 565 ( 96.6 % ) than in microscopy arm 19 , 545 ( 60.9 % ) [ RR : 1.59 ] . RDTs reduced patient waiting time compared to microscopy and were more convenient to health workers and patients . Majority 23 , 804 ( 99.7 % ) in presumptive arm were prescribed AL . All ( 100 % ) of patients who tested positive for malaria in RDT and microscopy arms were prescribed anti-malarials . Parasitological-based diagnosis significantly reduced AL prescription in RDT arm [ RR : 0.62 ] and microscopy arm [ RR : 0.72 ] compared to presumptive treatment . Among patients not tested in the two intervention arms , 12 , 044 ( 96.1 % ) in microscopy and 965 ( 61.6 % ) in RDT arm were treated with AL [ RR : 1.56 ] . Overall 10 , 558 ( 29.4 % ) with negative results [ 5 , 110 ( 23.4 % ) in RDT and 5 , 448 ( 39.0 % ) in microscopy arms ] were prescribed AL . Conclusion It was more feasible to implement parasite-based diagnosis for malaria using RDT than with microscopy . A high proportion of patients with negative malaria results are still prescribed anti-malarials . There is need to increase access to parasite-based diagnosis where microscopy is used . In order to fully harness the benefits of parasitological confirmation of malaria , it is necessary to reduce the prescription of anti-malarials in negative patients Background Inappropriate treatment of malaria is widely reported particularly in areas where there is poor access to health facilities and self-treatment of fevers with anti-malarial drugs bought in shops is the most common form of care-seeking . The main objective of the study was to examine the impact of introducing rapid diagnostic tests for malaria ( mRDTs ) in registered drug shops in Ug and a , with the aim to increase appropriate treatment of malaria with artemisinin-based combination therapy ( ACT ) in patients seeking treatment for fever in drug shops . Methods A cluster-r and omized trial of introducing mRDTs in registered drug shops was implemented in 20 geographical clusters of drug shops in Mukono district , central Ug and a. Ten clusters were r and omly allocated to the intervention ( diagnostic confirmation of malaria by mRDT followed by ACT ) and ten clusters to the control arm ( presumptive treatment of fevers with ACT ) . Treatment decisions by providers were vali date d by microscopy on a reference blood slide collected at the time of consultation . The primary outcome was the proportion of febrile patients receiving appropriate treatment with ACT defined as : malaria patients with microscopically-confirmed presence of parasites in a peripheral blood smear receiving ACT or rectal artesunate , and patients with no malaria parasites not given ACT . Findings A total of 15,517 eligible patients ( 8672 intervention and 6845 control ) received treatment for fever between January-December 2011 . The proportion of febrile patients who received appropriate ACT treatment was 72·9 % versus 33·7 % in the control arm ; a difference of 36·1 % ( 95 % CI : 21·3 – 50·9 ) , p<0·001 . The majority of patients with fever in the intervention arm accepted to purchase an mRDT ( 97·8 % ) , of whom 58·5 % tested mRDT-positive . Drug shop vendors adhered to the mRDT results , reducing over-treatment of malaria by 72·6 % ( 95 % CI : 46·7– 98·4 ) , p<0·001 ) compared to drug shop vendors using presumptive diagnosis ( control arm ) . Conclusion Diagnostic testing with mRDTs compared to presumptive treatment of fevers implemented in registered drug shops substantially improved appropriate treatment of malaria with ACT . Trial Registration Clinical Trials.gov NCT01194557 Background Early diagnosis , as well as prompt and effective treatment of uncomplicated malaria , are essential components of the anti-malaria strategy in Madagascar to prevent severe malaria , reduce mortality and limit malaria transmission . The purpose of this study was to assess the performance of the malaria rapid diagnostic tests ( RDTs ) used by community health workers ( CHWs ) by comparing RDT results with two reference methods ( microscopy and Polymerase Chain Reaction , PCR ) . Methods Eight CHWs in two districts , each with a different level of endemic malaria transmission , were trained to use RDTs in the management of febrile children under five years of age . RDTs were performed by CHWs in all febrile children who consulted for fever . In parallel , retrospective parasitological diagnoses were made by microscopy and PCR . The results of these different diagnostic methods were analysed to evaluate the diagnostic performance of the RDTs administered by the CHWs . The stability of the RDTs stored by CHWs was also evaluated . Results Among 190 febrile children with suspected malaria who visited CHWs between February 2009 and February 2010 , 89.5 % were found to be positive for malaria parasites by PCR , 51.6 % were positive by microscopy and 55.8 % were positive by RDT . The performance accuracy of the RDTs used by CHWs in terms of sensitivity , specificity , positive and negative predictive values was greater than 85 % . Concordance between microscopy and RDT , estimated by the Kappa value was 0.83 ( 95 % CI : 0.75 - 0.91 ) . RDTs stored by CHWs for 24 months were capable of detecting Plasmodium falciparum in blood at a level of 200 parasites/μl . Conclusion Introduction of easy-to-use diagnostic tools , such as RDTs , at the community level appears to be an effective strategy for improving febrile patient management and for reducing excessive use of anti-malarial drugs OBJECTIVES To assess if the clinical outcome of patients treated after performing a Rapid Diagnostic Test for malaria ( RDT ) is at least equivalent to that of controls ( treated presumptively without test ) and to determine the impact of the introduction of a malaria RDT on clinical decisions . METHODS R and omized , multi-centre , open clinical trial in two arms in 2006 at the end of the dry and of the rainy season in 10 peripheral health centres in Burkina Faso : one arm with use of RDT before treatment decision , one arm managed clinical ly . Primary endpoint : persistence of fever at day 4 . Secondary endpoints : frequency of malaria treatment and of antibiotic treatment . RESULTS A total of 852 febrile patients were recruited in the dry season and 1317 febrile patients in the rainy season , and r and omized either to be su bmi tted to RDT ( P_RTD ) or to be managed presumptively ( P_CLIN ) . In both seasons , no significant difference was found between the two r and omized groups in the frequency of antimalarial treatment , nor of antibiotic prescription . In the dry season , 80.8 % and 79.8 % of patients with a negative RDT were nevertheless diagnosed and treated for malaria , and so were 85.0 % and 82.6 % negative patients in the rainy season . In the rainy season only , both diagnosis and treatment of other conditions were significantly less frequent in RDT positive vs. negative patients ( 48.3 % vs. 61.4 % and 46.2 % vs. 59.9 % , P = 0.00 and 0.00 , respectively ) . CONCLUSION Our study was inconclusive on RDT safety ( clinical outcome in the two r and omized groups ) , because of an exceedingly and unexpectedly low compliance with the negative test result . Further research is needed on best strategies to promote adherence and on the safety of a test based strategy compared with the current , presumptive treatment strategy Background Accurate and practical malaria diagnostics , such as immunochromatographic rapid diagnostic tests ( RDTs ) , have the potential to avert unnecessary treatments and save lives . Volunteer community health workers ( CHWs ) represent a potentially valuable human re source for exp and ing this technology to where it is most needed , remote rural communities in sub-Saharan Africa with limited health facilities and personnel . This study reports on a training programme for CHWs to incorporate RDTs into their management strategy for febrile children in the Democratic Republic of Congo , a tropical African setting ravaged by human conflict . Methods Prospect i ve cohort study , satisfaction question naire and decision analysis . Results Twelve CHWs were trained to safely and accurately perform and interpret RDTs , then successfully implemented rapid diagnostic testing in their remote community in a cohort of 357 febrile children . CHWs were uniformly positive in evaluating RDTs for their utility and ease of use . However , high malaria prevalence in this cohort ( 93 % by RDTs , 88 % by light microscopy ) limited the cost-effectiveness of RDTs compared to presumptive treatment of all febrile children , as evidence d by findings from a simplified decision analysis . Conclusions CHWs can safely and effectively use RDTs in their management of febrile children ; however , cost-effectiveness of RDTs is limited in zones of high malaria prevalence Abstract Objectives : To assess the quality and safety of having community health workers ( CHWs ) in rural Zambia use rapid diagnostic tests ( RDTs ) and provide integrated management of malaria and pneumonia . Design / methods : In the context of a cluster-r and omized controlled trial of two models for community-based management of malaria and /or non-severe pneumonia in children under 5 years old , CHWs in the intervention arm were trained to use RDTs , follow a simple algorithm for classification and treat malaria with artemether – lumefantrine ( AL ) and pneumonia with amoxicillin . CHW records were review ed to assess the ability of the CHWs to appropriately classify and treat malaria and pneumonia , and account for supplies . Patients were also followed up to assess treatment safety . Results : During the 12-month study , the CHWs evaluated 1017 children with fever and /or fast/difficult breathing and performed 975 RDTs . Malaria and /or pneumonia were appropriately classified 94–100 % of the time . Treatment based on disease classification was correct in 94–100 % of episodes . Supply management was excellent with over 98 % of RDTs , amoxicillin , and AL properly accounted for . The use of RDTs , amoxicillin , and AL was associated with few minor adverse events . Most febrile children ( 90 % ) with negative RDT results recovered after being treated with an antipyretic alone . Conclusions : Volunteer CHWs in rural Zambia are capable of providing integrated management of malaria and pneumonia to children safely and at high quality Background Malaria is a major public health problem in Ug and a and the current policy recommends introduction of rapid diagnostic tests for malaria ( RDTs ) to facilitate effective case management . However , provision of RDTs in drug shops potentially raises a new set of issues , such as adherence to RDTs results , management of severe illnesses , referral of patients , and relationship with caretakers . The main objective of the study was to examine the impact of introducing RDTs in registered drug shops in Ug and a and document lessons and policy implication s for future scale-up of malaria control in the private health sector . Methods A cluster-r and omized trial introducing RDTs into registered drug shops was implemented in central Ug and a from October 2010 to July 2012 . An evaluation was undertaken to assess the impact and the processes involved with the introduction of RDTs into drug shops , the lessons learned and policy implication s. Results Introducing RDTs into drug shops was feasible . To scale-up this intervention however , drug shop practice s need to be regulated since the registration process was not clear , supervision was inadequate and record keeping was poor . Although initially it was anticipated that introducing a new practice of record keeping would be cumbersome , but at evaluation this was not found to be a constraint . This presents an important lesson for introducing health management information system into drug shops . Involving stakeholders , especially the district health team , in the design was important for ownership and sustainability . The involvement of village health teams in community sensitization to the new malaria treatment and diagnosis policy was a success and this strategy is recommended for future interventions . Conclusion Introducing RDTs into drug shops was feasible and it increased appropriate treatment of malaria with artemisinin-based combination therapy . It is anticipated that the lessons presented will help better implementation of similar interventions in the private sector Background Parasitological confirmation of malaria is now recommended in all febrile patients by the World Health Organization ( WHO ) to reduce inappropriate use of anti-malarial drugs . Widespread implementation of rapid diagnostic tests ( RDTs ) is regarded as an effective strategy to achieve this goal . However , the quality of diagnosis provided by RDTs in remote rural dispensaries and health centres is not ideal . Feasible RDT quality control programmes in these setting s are challenging . Collection of information regarding diagnostic events is also very deficient in low-re source countries . Methods A prospect i ve cohort of consecutive patients aged more than one year from both genders , seeking routine care for febrile episodes at dispensaries located in the Bagamoyo district of Tanzania , were enrolled into the study after signing an informed consent form . Blood sample s were taken for thick blood smear ( TBS ) microscopic examination and malaria RDT ( SD Bioline Malaria Antigen Pf/Pan ™ ( SD RDT ) ) . RDT results were interpreted by both visual interpretation and Deki Reader ™ device . Results of visual interpretation were used for case management purpose s. Microscopy was considered the “ gold st and ard test ” to assess the sensitivity and specificity of the Deki Reader interpretation and to compare it to visual interpretation . Results In total , 1,346 febrile subjects were included in the final analysis . The SD RDT , when used in conjunction with the Deki Reader and upon visual interpretation , had sensitivities of 95.3 % ( 95 % CI , 90.6 - 97.7 ) and 94.7 % ( 95 % CI , 89.8–97.3 ) respectively , and specificities of 94.6 % ( 95 % CI , 93.5–96.1 ) and 95.6 % ( 95 % CI , 94.2–96.6 ) , respectively to gold st and ard . There was a high percentage of overall agreement between the two methods of interpretation . Conclusion The sensitivity and specificity of the Deki Reader in interpretation of SD RDTs were comparable to previous reports and showed high agreement to visual interpretation ( > 98 % ) . The results of the study reflect the situation in real practice and show good performance characteristics of Deki Reader on interpreting malaria RDTs in the h and s of local laboratory technicians . They also suggest that a system like this could provide great benefits to the health care system . Further studies to look at ease of use by community health workers , and cost benefit of the system are warranted Background The intermittent screening and treatment ( IST ) of school children for malaria is one possible intervention strategy that could help reduce the burden of malaria among school children . Future implementation of IST will not only depend on its efficacy and cost-effectiveness but also on its acceptability to parents of the children who receive IST , as well as those responsible for its delivery . This study was conducted alongside a cluster-r and omized trial to investigate local perceptions of school-based IST among parents and other stakeholders on the Kenyan south coast . Methods Six out of the 51 schools receiving the IST intervention were purposively sample d , based on the prevalence of Plasmodium infection , to participate in the qualitative study . Twenty-two focus group discussion s and 17 in-depth interviews were conducted with parents and other key stakeholders involved in the implementation of school health programmes in the district . Data analysis was guided by the framework analysis method . Results High knowledge of the burden of clinical malaria on school children , the perceived benefits of preventing clinical disease through IST and previous positive experiences and interactions with other school health programmes facilitated the acceptability of IST . However , lack of underst and ing of the consequences of asymptomatic parasitaemia for apparently healthy school children could potentially contribute to non-adherence to treatment , and use of alternative anti-malarial drugs with simpler regimens was generally preferred . The general consensus of stakeholders was that health workers were best placed to undertake the screening and provide treatment , and although teachers ’ involvement in the programme is critical , most participants were opposed to teachers taking finger-prick blood sample s from children . There was also a strong dem and for the distribution of mosquito nets to augment IST . ConclusionS chool-based malaria control through IST was acceptable to most parents and other stakeholders , but careful consideration of the various roles of teachers , community health workers , and health workers , and the use of anti-malarial drugs with simpler regimens are critical to its future implementation Objective To examine the impact of providing rapid diagnostic tests for malaria on fever management in private drug retail shops where most poor rural people with fever present , with the aim of reducing current massive overdiagnosis and overtreatment of malaria . Design Cluster r and omized trial of 24 clusters of shops . Setting Dangme West , a poor rural district of Ghana . Participants Shops and their clients , both adults and children . Interventions Providing rapid diagnostic tests with realistic training . Main outcome measures The primary outcome was the proportion of clients testing negative for malaria by a double-read research blood slide who received an artemisinin combination therapy or other antimalarial . Secondary outcomes were use of antibiotics and antipyretics , and safety . Results Of 4603 clients , 3424 ( 74.4 % ) tested negative by double-read research slides . The proportion of slide-negative clients who received any antimalarial was 590/1854 ( 32 % ) in the intervention arm and 1378/1570 ( 88 % ) in the control arm ( adjusted risk ratio 0.41 ( 95 % CI 0.29 to 0.58 ) , P<0.0001 ) . Treatment was in high agreement with rapid diagnostic test result . Of those who were slide-positive , 690/787 ( 87.8 % ) in the intervention arm and 347/392 ( 88.5 % ) in the control arm received an artemisinin combination therapy ( adjusted risk ratio 0.96 ( 0.84 to 1.09 ) ) . There was no evidence of antibiotics being substituted for antimalarials . Overall , 1954/2641 ( 74 % ) clients in the intervention arm and 539/1962 ( 27 % ) in the control arm received appropriate treatment ( adjusted risk ratio 2.39 ( 1.69 to 3.39 ) , P<0.0001 ) . No safety concerns were identified . Conclusions Most patients with fever in Africa present to the private sector . In this trial , providing rapid diagnostic tests for malaria in the private drug retail sector significantly reduced dispensing of antimalarials to patients without malaria , did not reduce prescribing of antimalarials to true malaria cases , and appeared safe . Rapid diagnostic tests should be considered for the informal private drug retail sector . Registration Clinical trials.gov Rapid diagnostic tests ( RDTs ) were developed as an alternative to microscopy for malaria diagnosis . The RDTs detect malaria parasite antigen(s ) in whole blood with high sensitivity and specificity . We assessed health worker malaria treatment practice s after the introduction of RDTs in peripheral health facilities without microscopy . From December 2007 to October 2008 , we introduced histidine-rich protein II (HRP-2)-based ParaHIT RDTs for routine use in 12 health facilities in Rufiji District , Tanzania . Health workers received training on how to perform RDTs for patients 5 years of age or older with fever or suspected malaria . Children < 5 years of age were to be treated empirically per national guidelines . Among the 30,195 patients seen at these 12 health facilities , 10,737 ( 35.6 % ) were tested with an RDT for malaria . 88.3 % ( 9,405/10,648 ) of tested patients reported fever or history of fever and 2.7 % ( 289/10,677 ) of all tested individuals were children < 5 years of age . The RDT results were recorded for 10,650 patients ( 99.2 % ) . Among the 5,488 ( 51.5 % ) RDT-positive patients , 5,256 ( 98.6 % ) were treated with an appropriate first-line antimalarial per national guidelines ( artemether-lumefantrine or quinine ) . Among the 5,162 RDT-negative patients , only 205 ( 4.0 % ) were treated with an antimalarial . Other reported treatments included antibiotics and antipyretics . Implementation of RDTs in rural health facilities result ed in high adherence to national treatment guidelines . Patients testing negative by RDT were rarely treated with antimalarials . Unapproved antimalarials were seldom used . Health workers continued to follow guidelines for the empiric treatment of febrile children Malaria and pneumonia are leading causes of childhood mortality . Home Management of fever as Malaria ( HMM ) enables presumptive treatment with antimalarial drugs but excludes pneumonia . We aim ed to evaluate the impact of adding an antibiotic , amoxicillin ( AMX ) to an antimalarial , artesunate amodiaquine ( AAQ+AMX ) for treating fever among children 2–59 months of age within the HMM strategy on all-cause mortality . In a stepped-wedge cluster-r and omized , open trial , children 2–59 months of age with fever treated with AAQ or AAQ+AMX within HMM were compared with st and ard care . Mortality reduced significantly by 30 % ( rate ratio [ RR ] = 0.70 , 95 % confidence interval [ CI ] = 0.53– 0.92 , P = 0.011 ) in AAQ clusters and by 44 % ( RR = 0.56 , 95 % CI = 0.41–0.76 , P = 0.011 ) in AAQ+AMX clusters compared with control clusters . The 21 % mortality reduction between AAQ and AAQ+AMX ( RR = 0.79 , 95 % CI = 0.56 –1.12 , P = 0.195 ) was however not statistically significant . Community fever management with antimalarials significantly reduces under-five mortality . Given the lower mortality trend , adding an antibiotic is more beneficial Background Access to prompt and effective treatment is a cornerstone of the current malaria control strategy . Delays in starting appropriate treatment is a major contributor to malaria mortality . WHO recommends home management of malaria using artemisininbased combination therapy ( ACT ) and Rapid Diagnostic tests ( RDTs ) as one of the strategies for improving access to prompt and efective malaria case management . Methods A prospect i ve evaluation of the effectiveness of using community health workers ( CHWs ) as delivery points for ACT and RDTs in the home management of malaria in two districts in Zambia . Results CHWs were able to manage malaria fevers by correctly interpreting RDT results and appropriately prescribing antimalarials . All severe malaria cases and febrile non-malaria fevers were referred to a health facility for further management . There were variations in malaria prevalence between the two districts and among the villages in each district . 100 % and 99.4 % of the patients with a negative RDT result were not prescribed an antimalarial in the two districts respectively . No cases progressed to severe malaria and no deaths were recorded during the study period . Community perceptions were positive . Conclusion CHWs are effective delivery points for prompt and effective malaria case management at community level . Adherence to test results is the best ever reported in Zambia . Further areas of implementation research are discussed Shortly after Kenya introduced artemether-lumefantrine ( AL ) for first-line treatment of uncomplicated malaria , we conducted a pre-post cluster r and omized controlled trial to assess the effect of providing malaria rapid diagnostic tests ( RDTs ) on recommended treatment ( patients with malaria prescribed AL ) and overtreatment ( patients without malaria prescribed AL ) in out patients > /= 5 years old . Sixty health facilities were r and omized to receive either RDTs plus training , guidelines , and supervision ( TGS ) or TGS alone . Of 1,540 patients included in the analysis , 7 % had uncomplicated malaria . The provision of RDTs coupled with TGS emphasizing AL use only after laboratory confirmation of malaria reduced recommended treatment by 63%-points ( P = 0.04 ) , because diagnostic test use did not change ( -2%-points ) , but health workers significantly reduced presumptive treatment with AL for patients with a clinical diagnosis of malaria who did not undergo testing ( -36%-points ; P = 0.03 ) . Health workers generally adhered to RDT results when prescribing AL : 88 % of RDT-positive and 9 % of RDT-negative patients were treated with AL , respectively . Overtreatment was low in both arms and was not significantly reduced by the provision of RDTs ( -12%-points , P = 0.30 ) . RDTs could potentially improve malaria case management , but we urgently need to develop more effective strategies for implementing guidelines before large scale implementation Malaria is a major cause of morbidity and mortality among children under five in sub-Saharan Africa . Prompt diagnosis and adequate treatment of acute clinical episodes are essential to reduce morbidity and prevent complications and mortality . In many countries , chloroquine syrup is the mainstay of malaria treatment for children under five . Not only is syrup more expensive than tablets , adherence to the prescribed dose at home is a problem because mothers use wrongly sized measuring devices or have difficulty with the instructions . We investigated the impact of introducing pre-packed tablets for children on adherence to treatment and compared the total cost of the tablets with that of syrup . Children aged 0 - -5 years diagnosed with malaria at the clinic over a 6-week period received either pre-packed tablets or syrup by r and om assignment . The principal caregivers were interviewed at home on day 4 after attending the clinic . Of the 155 caregivers given pre-packed tablets , 91 % ( n=141 ) adhered to the recommended dosage , while only 42 % ( n=61 ) of 144 who were provided syrup did . Only 20 % of caregivers who received syrup used an accurate 5 ml measure . The cost of treatment with tablets was about one-quarter that of syrup and 62 % ( n=96 ) of caregivers preferred tablets . Pre-packed chloroquine tablets are a viable alternative to syrup BACKGROUND The scale-up of malaria rapid diagnostic tests ( RDTs ) is intended to improve case management of fever and targeting of artemisinin-based combination therapy . Habitual presumptive treatment has hampered these intentions , suggesting a need for strategies to support behaviour change . We aim ed to assess the introduction of RDTs when packaged with basic or enhanced clinician training interventions in Cameroon . METHODS We did a three-arm , stratified , cluster-r and omised trial at 46 public and mission health facilities at two study sites in Cameroon to compare three approaches to malaria diagnosis . Facilities were r and omly assigned by a computer program in a 9:19:19 ratio to current practice with microscopy ( widely available , used as a control group ) ; RDTs with a basic ( 1 day ) clinician training intervention ; or RDTs with an enhanced ( 3 days ) clinician training intervention . Patients ( or their carers ) and fieldworkers who administered surveys to obtain outcome data were masked to study group assignment . The primary outcome was the proportion of patients treated in accordance with WHO malaria treatment guidelines , which is a composite indicator of whether patients were tested for malaria and given appropriate treatment consistent with the test result . All analyses were by intention to treat . This study is registered at Clinical Trials.gov , number NCT01350752 . FINDINGS The study took place between June 7 and Dec 14 , 2011 . The analysis included 681 patients from nine facilities in the control group , 1632 patients from 18 facilities in the basic-training group , and 1669 from 19 facilities in the enhanced-training group . The proportion of patients treated in accordance with malaria guidelines did not improve with either intervention ; the adjusted risk ratio ( RR ) for basic training compared with control was 1·04 ( 95 % CI 0·53 - 2·07 ; p=0·90 ) , and for enhanced training compared with control was 1·17 ( 0·61 - 2·25 ; p=0·62 ) . Inappropriate use of antimalarial drugs after a negative test was reduced from 84 % ( 201/239 ) in the control group to 52 % ( 413/796 ) in the basic-training group ( unadjusted RR 0·63 , 0·28 - 1·43 ; p=0·25 ) and to 31 % ( 232/759 ) in the enhanced-training group ( 0·29 , 0·11 - 0·77 ; p=0·02 ) . INTERPRETATION Enhanced clinician training , design ed to translate knowledge into prescribing practice and improve quality of care , has the potential to halve overtreatment in public and mission health facilities in Cameroon . Basic training is unlikely to be sufficient to support the behaviour change required for the introduction of RDTs Background Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African setting s. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas . Diagnosis may be facilitated by malaria rapid diagnostic tests ( RDTs ) . In this study , the impact of a government policy change , comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals , was assessed by describing diagnostic behaviour and treatment decision-making in febrile out patients < 10 years of age in three hospitals in the Kagera and Mwanza Region in northern Tanzania . Methods Prospect i ve data from Biharamulo and Rubya Design ated District Hospital ( DDH ) were collected before and after policy change , in Sumve DDH no new policy was implemented . Diagnosis of malaria was confirmed by RDT ; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees . Results Prior to policy change , there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour . After policy change , there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics . The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1 % ( 244/274 ) to 38.7 % ( 46/119 ) in Biharamulo and from 76.9 % ( 190/247 ) to 10.0 % ( 48/479 ) in Rubya after policy change . Conclusion This study shows that an official policy change , where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour . The current findings are promising for improving treatment policy in Tanzanian hospitals |
12,164 | 27,182,986 | RESULTS A majority of the research supports the view that physical fitness , single bouts of PA , and PA interventions benefit children 's cognitive functioning .
Evidence indicates that PA has a relationship to areas of the brain that support complex cognitive processes during laboratory tasks .
The present systematic review found evidence to suggest that there are positive associations among PA , fitness , cognition , and academic achievement .
Regardless , the literature suggests no indication that increases in PA negatively affect cognition or academic achievement and PA is important for growth and development and general health .
Therefore , the evidence category rating is B. The literature suggests that PA and PE have a neutral effect on academic achievement . | BACKGROUND The relationship among physical activity ( PA ) , fitness , cognitive function , and academic achievement in children is receiving considerable attention .
The utility of PA to improve cognition and academic achievement is promising but uncertain ; thus , this position st and will provide clarity from the available science .
OBJECTIVE The purpose of this study was to answer the following questions : 1 ) among children age 5 - 13 yr , do PA and physical fitness influence cognition , learning , brain structure , and brain function ?
2 ) Among children age 5 - 13 yr , do PA , physical education ( PE ) , and sports programs influence st and ardized achievement test performance and concentration/attention ? | Background R and omized controlled trials ( RCT ) are required to test relationships between physical activity and cognition in children , but these must be informed by exploratory studies . This study aim ed to inform future RCT by : conducting practical utility and reliability studies to identify appropriate cognitive outcome measures ; piloting an RCT of a 10 week physical education ( PE ) intervention which involved 2 hours per week of aerobically intense PE compared to 2 hours of st and ard PE ( control ) . Methods 64 healthy children ( mean age 6.2 yrs SD 0.3 ; 33 boys ) recruited from 6 primary schools . Outcome measures were the Cambridge Neuropsychological Test Battery ( CANTAB ) , the Attention Network Test ( ANT ) , the Cognitive Assessment System ( CAS ) and the short form of the Connor 's Parent Rating Scale ( CPRS : S ) . Physical activity was measured habitually and during PE sessions using the Actigraph accelerometer . Results Test- retest intraclass correlations from CANTAB Spatial Span ( r 0.51 ) and Spatial Working Memory Errors ( 0.59 ) and ANT Reaction Time ( 0.37 ) and ANT Accuracy ( 0.60 ) were significant , but low . Physical activity was significantly higher during intervention vs. control PE sessions ( p < 0.0001 ) . There were no significant differences between intervention and control group changes in CAS scores . Differences between intervention and control groups favoring the intervention were observed for CANTAB Spatial Span , CANTAB Spatial Working Memory Errors , and ANT Accuracy . Conclusions The present study has identified practical and age-appropriate cognitive and behavioral outcome measures for future RCT , and identified that schools are willing to increase PE time . Trial registration numberIS RCT N70853932 ( http://www.controlled-trials.com Research supports the positive effects of exercise on cognitive performance by children . However , a limited number of studies have explored the effects specifically on memory . The purpose of this study was to compare the effects of an acute bout of exercise on learning , short-term memory , and long-term memory in a sample of children . Children were r and omly assigned to an exercise condition or to a no-treatment control condition and then performed repeated trials on an auditory verbal learning task . In the exercise condition , participants performed the PACER task , an aerobic fitness assessment , in their physical education class before performing the memory task . In the control condition , participants performed the memory task at the beginning of their physical education class . Results showed that participants in the exercise condition demonstrated significantly better learning of the word lists and significantly better recall of the words after a brief delay . There were not significant differences in recognition of the words after an approximately 24-hr delay . These results provide evidence in a school setting that an acute bout of exercise provides benefits for verbal learning and long-term memory . Future research should be design ed to identify the extent to which these findings translate to academic measures It is widely accepted that aerobic exercise enhances hippocampal plasticity . Often , this plasticity co-occurs with gains in hippocampal-dependent memory . Cross-sectional work investigating this relationship in preadolescent children has found behavioral differences in higher versus lower aerobically fit participants for tasks measuring relational memory , which is known to be critically tied to hippocampal structure and function . The present study tested whether similar differences would arise in a clinical intervention setting where a group of preadolescent children were r and omly assigned to a 9-month after school aerobic exercise intervention versus a wait-list control group . Performance measures included eye-movements as a measure of memory , based on recent work linking eye-movement indices of relational memory to the hippocampus . Results indicated that only children in the intervention increased their aerobic fitness . Compared to the control group , those who entered the aerobic exercise program displayed eye-movement patterns indicative of superior memory for face-scene relations , with no differences observed in memory for individual faces . The results of this intervention study provide clear support for the proposed linkage among the hippocampus , relational memory , and aerobic fitness , as well as illustrating the sensitivity of eye-movement measures as a means of assessing memory AIM to investigate whether increased physical exercise during the school day influenced subsequent cognitive performance in the classroom . METHOD a r and omized , crossover- design trial ( two weeks in duration ) was conducted in six mainstream primary schools ( 1224 children aged 8 - 11y ) . No data on sex was available . Children received a teacher-directed , classroom-based programme of physical exercise , delivered approximately 30 minutes after lunch for 15 minutes during one week and no exercise programme during the other ( order counterbalanced across participants ) . At the end of each school day , they completed one of five psychometric tests ( paced serial addition , size ordering , listening span , digit-span backwards , and digit-symbol encoding ) , so that each test was delivered once after exercise and once after no exercise . RESULTS general linear modelling analysis demonstrated a significant interaction between intervention and counterbalance group ( p<0.001 ) , showing that exercise benefitted cognitive performance . Post-hoc analysis revealed that benefits occurred in participants who received the exercise intervention in the second but not the first week of the experiment and were also moderated by type of test and age group . INTERPRETATION physical exercise benefits cognitive performance within the classroom . The degree of benefit depends on the context of testing and participants ' characteristics . This has implication s for the role that is attributed to physical exercise within the school curriculum The appropriateness of recess in the elementary program continues to be question ed although generally it is believed to be useful by elementary principals despite a dearth of supportive data . This study was a developmental study of the effects of physical activity on concentration . Comparison of passive and directed physical education activities on the concentration of second- , third- , and fourth- grade children was made . The Woodcock-Johnson Test of Concentration showed better performance by the fourth grade rs and within Grade 4 in favor of the physical activity group . A structured physical activity or a classroom activity immediately prior to a concentration task was not detrimental to children in Grade s 2 and 3 . Fourth- grade children performed significantly better on a test of concentration after engaging in a physical activity Abstract This study tested the association between aerobic fitness and executive function and the impact of enhanced , cognitively challenging physical activity on executive function in overweight and lean children . Seventy children aged 9–10 years were assigned to either a 6-month enhanced physical education programme including cognitively dem and ing ( open skill ) activities or curricular physical education only . Pre- and post-intervention tests assessed aerobic capacity ( Leger test ) and two components of executive function : inhibition and working memory updating ( r and om number generation task ) . Indices of inhibition and memory updating were compared in higher- and lower-fit children and intervention effects were evaluated as a function of physical activity programme ( enhanced vs. curricular ) and weight status ( lean vs. overweight ) . Results showed better inhibition in higher- than lower-fit children , extending the existing evidence of the association between aerobic fitness and executive function to new aspects of children ’s inhibitory ability . Overweight children had more pronounced pre- to post-intervention improvements in inhibition than lean children only if involved in enhanced physical education . Such intervention effects were not mediated by aerobic fitness gains . Therefore , the cognitive and social interaction challenges inherent in open skill tasks , even though embedded in a low-dose physical activity programme , may represent an effective means to promote cognitive efficiency , especially in overweight children BACKGROUND The present study examined whether aerobic fitness training of older humans can increase brain volume in regions associated with age-related decline in both brain structure and cognition . METHODS Fifty-nine healthy but sedentary community-dwelling volunteers , aged 60 - 79 years , participated in the 6-month r and omized clinical trial . Half of the older adults served in the aerobic training group , the other half of the older adults participated in the toning and stretching control group . Twenty young adults served as controls for the magnetic resonance imaging ( MRI ) , and did not participate in the exercise intervention . High spatial resolution estimates of gray and white matter volume , derived from 3D spoiled gradient recalled acquisition MRI images , were collected before and after the 6-month fitness intervention . Estimates of maximal oxygen uptake ( VO2 ) were also obtained . RESULTS Significant increases in brain volume , in both gray and white matter regions , were found as a function of fitness training for the older adults who participated in the aerobic fitness training but not for the older adults who participated in the stretching and toning ( nonaerobic ) control group . As predicted , no significant changes in either gray or white matter volume were detected for our younger participants . CONCLUSIONS These results suggest that cardiovascular fitness is associated with the sparing of brain tissue in aging humans . Furthermore , these results suggest a strong biological basis for the role of aerobic fitness in maintaining and enhancing central nervous system health and cognitive functioning in older adults OBJECTIVE : To assess the effect of a physical activity ( PA ) intervention on brain and behavioral indices of executive control in preadolescent children . METHODS : Two hundred twenty-one children ( 7–9 years ) were r and omly assigned to a 9-month afterschool PA program or a wait-list control . In addition to changes in fitness ( maximal oxygen consumption ) , electrical activity in the brain ( P3-ERP ) and behavioral measures ( accuracy , reaction time ) of executive control were collected by using tasks that modulated attentional inhibition and cognitive flexibility . RESULTS : Fitness improved more among intervention participants from pretest to posttest compared with the wait-list control ( 1.3 mL/kg per minute , 95 % confidence interval [ CI ] : 0.3 to 2.4 ; d = 0.34 for group difference in pre-to-post change score ) . Intervention participants exhibited greater improvements from pretest to posttest in inhibition ( 3.2 % , 95 % CI : 0.0 to 6.5 ; d = 0.27 ) and cognitive flexibility ( 4.8 % , 95 % CI : 1.1 to 8.4 ; d = 0.35 for group difference in pre-to-post change score ) compared with control . Only the intervention group increased attentional re sources from pretest to posttest during tasks requiring increased inhibition ( 1.4 µV , 95 % CI : 0.3 to 2.6 ; d = 0.34 ) and cognitive flexibility ( 1.5 µV , 95 % CI : 0.6 to 2.5 ; d = 0.43 ) . Finally , improvements in brain function on the inhibition task ( r = 0.22 ) and performance on the flexibility task correlated with intervention attendance ( r = 0.24 ) . CONCLUSIONS : The intervention enhanced cognitive performance and brain function during tasks requiring greater executive control . These findings demonstrate a causal effect of a PA program on executive control , and provide support for PA for improving childhood cognition and brain health PURPOSE This study was conducted to determine the effect of physical education class enrollment and physical activity on academic achievement in middle school children . METHODS Participants were 214 sixth- grade students r and omly assigned to physical education during either first or second semesters . Moderate and vigorous physical activity ( MVPA ) ( number of 30-min time blocks ) outside of school was assessed using the 3-d physical activity recall ( 3DPAR ) . The 3DPAR time blocks were converted to ordinal data with scores of 1 ( no activity ) , 2 ( some activity ) , or 3 ( activity meeting Healthy People 2010 guidelines ) . Academic achievement was assessed using grade s from four core academic classes and st and ardized test scores ( Terra Nova percentiles ) . RESULTS Grade s were similar regardless of whether students were enrolled in physical education during first or second semesters . Physical education classes averaged only 19 min of MVPA . Students who either performed some or met Healthy People 2010 guidelines for vigorous activity had significantly higher grade s ( P < 0.05 ) than students who performed no vigorous activity in both semesters . Moderate physical activity did not affect grade s. St and ardized test scores were not significantly related to physical education class enrollment or physical activity levels . CONCLUSION Although academic achievement was not significantly related to physical education enrollment , higher grade s were associated with vigorous physical activity , particularly activity meeting recommended Healthy People 2010 levels This individual differences study examined the separability of three often postulated executive functions-mental set shifting ( " Shifting " ) , information updating and monitoring ( " Updating " ) , and inhibition of prepotent responses ("Inhibition")- and their roles in complex " frontal lobe " or " executive " tasks . One hundred thirty-seven college students performed a set of relatively simple experimental tasks that are considered to predominantly tap each target executive function as well as a set of frequently used executive tasks : the Wisconsin Card Sorting Test ( WCST ) , Tower of Hanoi ( TOH ) , r and om number generation ( RNG ) , operation span , and dual tasking . Confirmatory factor analysis indicated that the three target executive functions are moderately correlated with one another , but are clearly separable . Moreover , structural equation modeling suggested that the three functions contribute differentially to performance on complex executive tasks . Specifically , WCST performance was related most strongly to Shifting , TOH to Inhibition , RNG to Inhibition and Updating , and operation span to Updating . Dual task performance was not related to any of the three target functions . These results suggest that it is important to recognize both the unity and diversity of executive functions and that latent variable analysis is a useful approach to study ing the organization and roles of executive functions Children with low aerobic fitness have altered brain function compared to higher-fit children . This study examined the effect of an 8-month exercise intervention on resting state synchrony . Twenty-two sedentary , overweight ( body mass index ≥85th percentile ) children 8 - 11 years old were r and omly assigned to one of two after-school programs : aerobic exercise ( n=13 ) or sedentary attention control ( n=9 ) . Before and after the 8-month programs , all subjects participated in resting state functional magnetic resonance imaging scans . Independent components analysis identified several networks , with four chosen for between-group analysis : salience , default mode , cognitive control , and motor networks . The default mode , cognitive control , and motor networks showed more spatial refinement over time in the exercise group compared to controls . The motor network showed increased synchrony in the exercise group with the right medial frontal gyrus compared to controls . Exercise behavior may enhance brain development in children PURPOSE To examine the impact of integrating physical activity with elementary curricula on fluid intelligence and academic achievement . METHODS A r and om sample of 3rd grade teachers integrated physical activity into their core curricula approximately 30 minutes a day , 3 days a week from January 2008 to April 2008 . Noninvasive fluid intelligence cognitive measures were used along with State-m and ated academic achievement tests . RESULTS Experimental Group children averaged close to 1200 pedometer steps per integration day , thus averaging 3600 steps per week . Children in the Experimental Group performed significantly better on the SPM Fluid Intelligence Test . Children in the Experimental Group also performed significantly better on the Social Studies State m and ated academic achievement test . Experimental Group children also received higher scores on the English/ Language Arts , Math and Science achievements tests , but were not statistically significant compared with Control Group children . Children classified in Fitnessgram 's Healthy Fitness Zone for BMI earned lower scores on many of the SPM Fluid Intelligence components . DISCUSSION This investigation provides evidence that movement can influence fluid intelligence and should be considered to promote cognitive development of elementary-age children . Equally compelling were the differences in SPM Fluid Intelligence Test scores for children who were distinguished by Fitnessgram 's BMI cut points The aim of the present study was to examine the combined effects of breakfast glycaemic index ( GI ) and a mid-morning bout of exercise on adolescents ' cognitive function . Participants were r and omly allocated to a high or low GI breakfast group in a mixed research design , where each participant completed two experimental trials ( exercise and resting ) . Forty-two adolescents ( 12.4±0.5 years old ) , undertook a bout of exercise ( ten repeats of level one of the multi-stage fitness test ; exercise trial ) or continued to rest ( resting trial ) following consumption of either a high or low GI breakfast . A battery of cognitive function tests ( visual search test , Stroop test and Sternberg paradigm ) was completed 30 min before and 45 min following the exercise . Average heart rate during exercise was 170±15 beats·min(-1 ) . On the complex level of the Stroop test , response times improved across the morning following the low GI breakfast on both the exercise and resting trials , though the improvement was greatest on the exercise trial . However , response times only improved on the resting trial following the high GI breakfast ( p=0.012 ) . On the 5 letter level of the Sternberg paradigm , response times improved across the morning following the low GI breakfast ( regardless of exercise ) and only on the exercise trial following the high GI breakfast ( p=0.019 ) . The findings of the present study suggest that the combined effects of breakfast GI and exercise in adolescents depend upon the component of cognitive function examined . A low GI breakfast and mid-morning bout of exercise were individually beneficial for response times on the Sternberg paradigm , whereas they conferred additional benefits for response times on the Stroop test In childhood , excess adiposity and low fitness are linked to poor academic performance , lower cognitive function , and differences in brain structure . Identifying ways to mitigate obesity-related alterations is of current clinical importance . This study examined the effects of an 8-month exercise intervention on the uncinate fasciculus , a white matter fiber tract connecting frontal and temporal lobes . Participants consisted of 18 unfit , overweight 8- to 11-year-old children ( 94 % Black ) who were r and omly assigned to either an aerobic exercise ( n = 10 ) or a sedentary control group ( n = 8) . Before and after the intervention , all subjects participated in a diffusion tensor MRI scan . Tractography was conducted to isolate the uncinate fasciculus . The exercise group showed improved white matter integrity as compared to the control group . These findings are consistent with an emerging literature suggesting beneficial effects of exercise on white matter integrity OBJECTIVE This experiment tested the hypothesis that exercise would improve executive function . DESIGN Sedentary , overweight 7- to 11-year-old children ( N = 171 , 56 % girls , 61 % Black , M ± SD age = 9.3 ± 1.0 years , body mass index [ BMI ] = 26 ± 4.6 kg/m² , BMI z-score = 2.1 ± 0.4 ) were r and omized to 13 ± 1.6 weeks of an exercise program ( 20 or 40 min/day ) , or a control condition . MAIN OUTCOME MEASURES Blinded , st and ardized psychological evaluations ( Cognitive Assessment System and Woodcock-Johnson Tests of Achievement III ) assessed cognition and academic achievement . Functional MRI measured brain activity during executive function tasks . RESULTS Intent to treat analysis revealed dose-response benefits of exercise on executive function and mathematics achievement . Preliminary evidence of increased bilateral prefrontal cortex activity and reduced bilateral posterior parietal cortex activity attributable to exercise was also observed . CONCLUSION Consistent with results obtained in older adults , a specific improvement on executive function and brain activation changes attributable to exercise were observed . The cognitive and achievement results add evidence of dose-response and extend experimental evidence into childhood . This study provides information on an educational outcome . Besides its importance for maintaining weight and reducing health risks during a childhood obesity epidemic , physical activity may prove to be a simple , important method of enhancing aspects of children 's mental functioning that are central to cognitive development . This information may persuade educators to implement vigorous physical activity 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 The present study examined the effects of a 9-month r and omized control physical activity intervention aim ed at improving cardiorespiratory fitness on changes in working memory performance in preadolescent children relative to a waitlist control group . Participants performed a modified Sternberg task , which manipulated working memory dem and s based on encoding set sizes , while task performance and the contingent negative variation ( CNV ) event-related brain potential were measured . Analyses revealed that the physical activity intervention led to increases in cardiorespiratory fitness and improved Sternberg task performance . Further , the beneficial effects of the physical activity intervention were greater for a task condition requiring greater working memory dem and s. In addition , the intervention group exhibited larger initial CNV at the frontal electrode site , relative to the waitlist group at post-test ; an effect not observed during the pre-test . These results indicate that increases in cardiorespiratory fitness are associated with improvements in the cognitive control of working memory in preadolescent children Aerobic fitness is associated with white matter integrity ( WMI ) in adults as measured by diffusion tensor imaging ( DTI ) . This study examined the effect of an 8-month exercise intervention on WMI in children . Participants were 18 sedentary , overweight ( BMI ≥85th percentile ) 8- to 11-year-old children ( 94 % Black ) , r and omly assigned to either an aerobic exercise ( n = 10 ) or sedentary attention control group ( n = 8) . Each group was offered an instructor-led after-school program every school day for approximately 8 months . Before and after the program , all subjects participated in DTI scans . Tractography was conducted to isolate the superior longitudinal fasciculus and investigate whether the exercise intervention affected WMI in this region . There was no group by time interaction for WMI in the superior longitudinal fasciculus . There was a group by time by attendance interaction , however , such that higher attendance at the exercise intervention , but not the control intervention , was associated with increased WMI . Heart rate and the total dose of exercise correlated with WMI changes in the exercise group . In the overall sample , increased WMI was associated with improved scores on a measure of attention and improved teacher ratings of executive function . This study indicates that participating in an exercise intervention improves WMI in children as compared to a sedentary after-school program PURPOSE This study evaluated the effects of a classroom-based physical activity program on children 's in-school physical activity levels and on-task behavior during academic instruction . METHODS Physical activity of 243 students was assessed during school hours . Intervention-group students ( N = 135 ) received a classroom-based program ( i.e. , Energizers ) . The control group ( N = 108 ) did not receive Energizers . On-task behavior during academic instruction time was observed for 62 third- grade ( N = 37 ) and fourth- grade students ( N = 25 ) before and after Energizers activities . An independent groups t-test compared in-school physical activity levels between intervention and control classes . A multiple-baseline across-classrooms design was used to evaluate the effectiveness of the Energizers on on-task behavior . Additionally , a two-way ( time [ pre- vs postobservation ] x period [ baseline vs intervention ] ) repeated- measures analysis of variance compared on-task behavior between observation periods . Magnitudes of mean differences were evaluated with Cohen 's delta ( ES ) . RESULTS Students in the intervention group took significantly ( P < 0.05 ) more in-school steps ( 5587 + /- 1633 ) than control-group students ( 4805 + /- 1543 ) , and the size of this difference was moderate ( ES = 0.49 ) . The intervention was effective in improving on-task behavior ; after the Energizers were systematic ally implemented , on-task behavior systematic ally improved . The improvement in on-task behavior of 8 % between the pre-Energizers and post-Energizers observations was statistically significant ( P < 0.017 ) , and the difference was moderate ( ES = 0.60 ) . Likewise , the least on-task students improved on-task behavior by 20 % after Energizers activities . This improvement was statistically significant ( P < 0.001 ) and meaningful ( ES = 2.20 ) . CONCLUSION A classroom-based physical activity program was effective for increasing daily in-school physical activity and improving on-task behavior during academic instruction BACKGROUND This study examined associations of fitness and fatness with cognitive processes , academic achievement , and behavior , independent of demographic factors , at the baseline of an exercise trial . METHODS Overweight , sedentary but otherwise healthy 7 - 11 year olds ( N=170 ) participated in a study of health , cognition and achievement in the Augusta , GA area from 2003 - 2006 . Children underwent evaluations of fatness and fitness , psychological assessment s of cognition and academic achievement , and behavior ratings by parents and teachers . Partial correlations examined associations of fitness and fatness with cognitive and achievement scores and behavior ratings , controlling for demographic factors . RESULTS Fitness was associated with better cognition , achievement and behavior , and fatness with worse scores . Specifically , executive function , mathematics and reading achievement , and parent ratings of child behavior were related to fitness and fatness . Teacher ratings were related to fitness . CONCLUSION These results extend prior studies by providing reliable , st and ardized measures of cognitive processes , achievement , and behavior in relation to detailed measures of fitness and fatness . However , cross-sectional associations do not necessarily indicate that improving one factor , such as fatness or fitness , will result in improvements in factors that were associated with it . Thus , r and omized clinical trials are necessary to determine the effects of interventions OBJECTIVE Children who are less fit reportedly have lower performance on tests of cognitive control and differences in brain function . This study examined the effect of an exercise intervention on brain function during two cognitive control tasks in overweight children . DESIGN AND METHODS Participants included 43 unfit , overweight ( BMI ≥ 85th percentile ) children 8- to 11-years old ( 91 % Black ) , who were r and omly divided into either an aerobic exercise ( n = 24 ) or attention control group ( n = 19 ) . Each group was offered a separate instructor-led after-school program every school day for 8 months . Before and after the program , all children performed two cognitive control tasks during functional magnetic resonance imaging ( fMRI ) : antisaccade and flanker . RESULTS Compared to the control group , the exercise group decreased activation in several regions supporting antisaccade performance , including pre central gyrus and posterior parietal cortex , and increased activation in several regions supporting flanker performance , including anterior cingulate and superior frontal gyrus . CONCLUSIONS Exercise may differentially impact these two task conditions , or the paradigms in which cognitive control tasks were presented may be sensitive to distinct types of brain activation that show different effects of exercise . In sum , exercise appears to alter efficiency or flexible modulation of neural circuitry supporting cognitive control in overweight children BACKGROUND Physical Activity Across the Curriculum ( PAAC ) was a three-year cluster r and omized controlled trial to promote physical activity and diminish increases in overweight and obesity in elementary school children . METHODS Twenty-four elementary schools were cluster r and omized to the Physical Activity Across the Curriculum intervention or served as control . All children in grade s two and three were followed to grade s four and five . Physical Activity Across the Curriculum promoted 90 min/wk of moderate to vigorous intensity physically active academic lessons delivered by classroom teachers . Body Mass Index was the primary outcome , daily Physical activity and academic achievement were secondary outcomes . RESULTS The three-year change in Body Mass Index for Physical Activity Across the Curriculum was 2.0+/-1.9 and control 1.9+/-1.9 , respectively ( NS ) . However , change in Body Mass Index from baseline to 3 years was significantly influenced by exposure to Physical Activity Across the Curriculum . Schools with > or = 75 min of Physical Activity Across the Curriculum/wk showed significantly less increase in Body Mass Index at 3 years compared to schools that had < 75 min of Physical Activity Across the Curriculum ( 1.8+/-1.8 vs. 2.4+/-2.0 , p=0.02 ) . Physical Activity Across the Curriculum schools had significantly greater changes in daily Physical activity and academic achievement scores . CONCLUSIONS The Physical Activity Across the Curriculum approach may promote daily Physical activity and academic achievement in elementary school children . Additionally , 75 min of Physical Activity Across the Curriculum activities may attenuate increases in Body Mass Index The effects of a 2-year health-related school physical education program on st and ardized academic achievement scores was assessed in 759 children who completed Metropolitan Achievement Tests before and after the program . Schools were r and omly assigned to condition : ( a ) Specialists taught the Sports , Play , and Active Recreation for Kids curriculum ; ( b ) classroom teachers were trained to implement the curriculum ; and ( c ) controls continued their usual programs . The Trained Teacher condition was superior to Control on Language , Reading , and Basic Battery . The Specialist condition was superior to Control on Reading , but inferior on Language . Despite devoting twice as many minutes per week to physical education as Controls , the health-related physical education program did not interfere with academic achievement . Health-related physical education may have favorable effects on students ' academic achievement 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 PURPOSE The purpose of this study was twofold : 1 ) to evaluate the effectiveness of a school-based physical activity intervention , Action Schools ! BC ( AS ! BC ) , for maintaining academic performance in a multiethnic group of elementary children , and 2 ) to determine whether boys and girls ' academic performance changed similarly after participation in AS ! BC . METHODS This was a 16-month cluster r and omized controlled trial . Ten schools were r and omized to intervention ( INT ) or usual practice ( UP ) . One INT school administered the wrong final test , and one UP school grade d their own test , so both were excluded . Thus , eight schools ( six INT , two UP ) were included in the final analysis . Children ( 143 boys , 144 girls ) in grade s 4 and 5 were recruited for the study . We used the Canadian Achievement Test ( CAT-3 ) to evaluate academic performance ( TotScore ) . Weekly teacher activity logs determined amounts of physical activity delivered by teachers to students . Physical activity was determined with the Physical Activity Question naire for Children ( PAQ-C ) . Independent t-tests compared descriptive variables between groups and between boys and girls . We used a mixed linear model to evaluate differences in TotScore at follow-up between groups and between girls and boys . RESULTS Physical activity delivered by teachers to children in INT schools was increased by 47 min x wk(-1 ) ( 139 + /- 62 vs 92 + /- 45 , P < 0.001 ) . Participants attending UP schools had significantly higher baseline TotScores than those attending INT schools . Despite this , there was no significant difference in TotScore between groups at follow-up and between boys and girls at baseline and follow-up . CONCLUSION The AS ! BC model is an attractive and feasible intervention to increase physical activity for students while maintaining levels of academic performance OBJECT Increased importance on academic achievement has result ed in many school districts focusing on improved academic performance leading to reductions in physical education time . The purpose was to examine the effects of 45 minutes of daily physical education on the cognitive ability , fitness performance and body composition of African American elementary and middle school youth . METHODS Participants completing the informed consent in grade s 2nd to 8th were included in the study . A pre/posttest design was used with repeated measures analysis of variance . Experimental and control school participants were pretested on the cognitive measures ( ie , Fluid Intelligence and Perceptual Speed ) and Fitnessgram ® physical fitness test items ( eg , aerobic capacity , muscular strength and muscular endurance , body composition ) in September 2009 and posttested in May 2010 . RESULTS Experimental elementary and middle school participants observed significantly greater improvements compared with control elementary and middle school participants on 7 of 16 fitness and body composition measures and on 8 of 26 cognitive measures . These fitness , body composition , and cognitive improvement differences were more noticeable among elementary and middle school females . CONCLUSIONS Providing 45 minutes of daily physical education can perhaps increase cognitive ability while increasing fitness and decreasing the prevalence of overweight and obese youth The intent of this investigation was to examine the potential influence of varying duration s of physical exertion at different times of the day on immediate mathematical performance by 120 sixth- grade boys and girls . Subjects were assigned to two control and two treatment groups ( Solomon Four-group Design ) , with treated subjects administered physical exertion ( paced walking at controlled moderate intensity ) for duration s of 20 , 30 , and 40 min . at three different times of the school day [ 8:30 a.m. , 11:50 a.m. ( before lunch ) , 2:20 p.m. ] over 3 weeks . After each exertion session , subjects were immediately administered a 90-sec . mathematical computation test . Analysis indicated no significant differences in mathematical performance at any duration in the morning , but scores were significantly higher at 11:50 a.m. and 2:20 p.m. at 30- and 40-min . duration s in comparison to the 20-min . duration . There were no differences by gender of subject BACKGROUND There is a paucity of research investigating the effects of innovative physical activity programs on physical health and academic performance in the Latino population . PURPOSE To examine the impact of Dance Dance Revolution [DDR]-based exercise on Latino children 's physical fitness and academic achievement . DESIGN A repeated- measures crossover design was used . In Year 1 , Grade -4 students were assigned to the intervention group and offered 30 minutes of exercise ( DDR , aerobic dance ) three times per week . Grade -3 and Grade -5 students made up the comparison group and were offered no structured exercise at school . In Year 2 , the Grade -4 students were again assigned to the intervention , whereas Grade -5 and Grade -6 students were in the comparison group . SETTING / PARTICIPANTS Assessment s were conducted with 208 Latino school children . MAIN OUTCOME MEASURES The baseline measures included time to complete a 1-mile run , BMI , and reading and math scores . Data were collected again 9 months later . Overall , data were collected in 2009 - 2011 and analyzed in 2012 . RESULTS Data yielded significant differences between the intervention and comparison groups in differences in 1-mile run and math scores in Year 1 and Year 2 . The results also revealed net differences in the intervention versus comparison group scores on the 1-mile run for Grade 3 ( p<0.01 ) . Additionally , children 's yearly pre-test and post-test BMI group changes differed ( χ(2)((2 ) ) = 6.6 , p<0.05 ) only for the first year of intervention . CONCLUSIONS The DDR-based exercise intervention improved children 's cardiorespiratory endurance and math scores over time . Professionals should consider integrating exergaming at schools to achieve the goals of promoting a physically active lifestyle and enhancing academic success among Latino children The study tested the effect of aerobic exercise training on executive function in overweight children . Ninety-four sedentary , overweight but otherwise healthy children ( mean age = 9.2 years , body mass index 85th percentile ) were r and omized to a low-dose ( 20 min/day exercise ) , high-dose ( 40 min/day exercise ) , or control condition . Exercise sessions met 5 days/week for 15 weeks . The Cognitive Assessment System ( CAS ) , a st and ardized test of cognitive processes , was administered individually before and following intervention . Analysis of covariance on posttest scores revealed effects on executive function . Group differences emerged for the CAS Planning scale ( p = .03 ) . Planning scores for the high-dose group were significantly greater than those of the control group . Exercise may prove to be a simple , yet important , method of enhancing aspects of children 's mental functioning that are central to cognitive and social development OBJECTIVE The objective of this study was to assess the effect of yoga , compared to physical activity on the cognitive performance in 7 - 9 year-old schoolchildren from a socioeconomic disadvantaged background . DESIGN Two hundred ( 200 ) schoolchildren from Bangalore , India , after baseline assessment of cognitive functioning were r and omly allocated to either a yoga or a physical-activity group . Cognitive functions ( attention and concentration , visuo-spatial abilities , verbal ability , and abstract thinking ) were assessed using an Indian adaptation of the Wechsler Intelligence Scale for Children at baseline , after 3 months of intervention , and later at a 3-month follow-up . RESULTS Of the 200 subjects , 193 were assessed at 3 months after the study , and then 180 were assessed at the 3-month follow-up . There were no significant differences in cognitive performance between the two study groups ( yoga versus physical activity ) at postintervention , after controlling for grade levels . Improvement in the mean scores of cognitive tests following intervention varied from 0.5 ( Arithmetic ) to 1.4 ( Coding ) for the yoga group and 0.7 ( Arithmetic ) to 1.6 ( Vocabulary ) in the physical-activity group . CONCLUSIONS Yoga was as effective as physical activity in improving cognitive performance in 7 - 9 year old schoolchildren . Further studies are needed to examine the dose-response relationship between yoga and cognitive performance The amount of time allocated to physical activity in schools is declining . Time-efficient physical activity solutions that demonstrate their impact on academic achievement-related outcomes are needed to prioritize physical activity within the school curricula . " FUNtervals " are 4-min , high-intensity interval activities that use whole-body actions to complement a storyline . The purpose of this study was to ( i ) explore whether FUNtervals can improve selective attention , an executive function posited to be essential for learning and academic success ; and ( ii ) examine whether this relationship is predicted by students ' classroom off-task behaviour . Seven grade 3 - 5 classes ( n = 88 ) were exposed to a single-group , repeated cross-over design where each student 's selective attention was compared between no-activity and FUNtervals days . In week 1 , students were familiarized with the d2 test of attention and FUNterval activities , and baseline off-task behaviour was observed . In both weeks 2 and 3 students completed the d2 test of attention following either a FUNterval break or a no-activity break . The order of these breaks was r and omized and counterbalanced between weeks . Neither motor nor passive off-task behaviour predicted changes in selective attention following FUNtervals ; however , a weak relationship was observed for verbal off-task behaviour and improvements in d2 test performance . More importantly , students made fewer errors during the d2 test following FUNtervals . In supporting the priority of physical activity inclusion within schools , FUNtervals , a time efficient and easily implemented physical activity break , can improve selective attention in 9- to 11-year olds |
12,165 | 25,060,160 | Conclusion This systematic review demonstrates inconsistencies in describing educational interventions for EBP in r and omised and non-r and omised trials . | Abstract Background The aim of this systematic review was to identify which information is included when reporting educational interventions used to facilitate foundational skills and knowledge of evidence -based practice ( EBP ) training for health professionals .
This systematic review comprised the first stage in the three stage development process for a reporting guideline for educational interventions for EBP .
Methods The review question was ‘ What information has been reported when describing educational interventions targeting foundational evidence -based practice knowledge and skills ? ’ | Abstract OBJECTIVE : To determine if a simple educational intervention can increase resident physician literature search activity . DESIGN : R and omized controlled trial . SETTING : University hospital-based internal medicine training program . PATIENTS / PARTICIPANTS : Forty-eight medical residents rotating on the general internal medicine service . INTERVENTIONS : One-hour didactic session , the use of well-built clinical question cards , and practical sessions in clinical question building . MEASUREMENTS AND MAIN RESULTS : Objective data from the library information system that included the number of log-ons to MEDLINE , search ing volume , abstract s viewed , full-text articles viewed , and time spent search ing . Median search activity as measured per person per week ( control vs intervention ) : number of log-ons to MEDLINE ( 2.1 vs 4.4 , P<.001 ) ; total number of search sets ( 24.0 vs 74.2 , P<.001 ) ; abstract s viewed ( 5.8 vs 17.7 , P=.001 ) ; articles viewed ( 1.0 vs 2.6 , P=.005 ) ; and hours spent search ing ( 0.8 vs 2.4 , P<.001 ) . CONCLUSIONS : A simple educational intervention can markedly increase resident search ing activity Background Supporting 21st century health care and the practice of evidence -based medicine ( EBM ) requires ubiquitous access to clinical information and to knowledge-based re sources to answer clinical questions . Many questions go unanswered , however , due to lack of skills in formulating questions , crafting effective search strategies , and accessing data bases to identify best levels of evidence . Methods This r and omized trial was design ed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system . Two of the search interfaces utilized a specific framework called PICO , which was design ed to focus clinical questions and to prompt for publication type or type of question asked . The third interface was the st and ard PubMed interface readily available on the Web . Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US . Thirty-one subjects were r and omized to one of the three interfaces , given 3 clinical questions , and asked to search PubMed for a set of relevant articles that would provide an answer for each question . The success of the search results was determined by a precision score , which compared the number of relevant or gold st and ard articles retrieved in a result set to the total number of articles retrieved in that set . Results Participants using the PICO templates ( Protocol A or Protocol B ) had higher precision scores for each question than the participants who used Protocol C , the st and ard PubMed Web interface . ( Question 1 : A = 35 % , B = 28 % , C = 20 % ; Question 2 : A = 5 % , B = 6 % , C = 4 % ; Question 3 : A = 1 % , B = 0 % , C = 0 % ) 95 % confidence intervals were calculated for the precision for each question using a lower boundary of zero . However , the 95 % confidence limits were overlapping , suggesting no statistical difference between the groups . Conclusion Due to the small number of search es for each arm , this pilot study could not demonstrate a statistically significant difference between the search protocol s. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results PURPOSE The study assesses potential for improving residents ' evidence -based medicine search ing skills in MEDLINE through real-time librarian instruction . SUBJECTS Ten residents on a rotation in a neonatal intensive care unit participated . METHODOLOGY Residents were r and omized into an instruction and a non-instruction group . Residents generated questions from rounds and search ed MEDLINE for answers . Data were collected through observation , search strategy analysis , and surveys . Librarians observed search es and collected data on questions , search ing skills , search problems , and the test group 's instruction topics . Participants performed st and ardized search es before , after , and six-months after intervention and were scored using a search strategy analysis tool ( 1 representing highest score and 5 representing lowest score ) . Residents completed pre- and post-intervention surveys to measure opinions about MEDLINE and search satisfaction . RESULTS Post-intervention , the test group formulated better questions , used limits more effectively , and reported greater confidence in using MEDLINE . The control group expressed less satisfaction with retrieval and demonstrated more errors when limiting . The test and control groups had the following average search scores respectively : 3.0 and 3.5 ( pre-intervention ) , 3.3 and 3.4 ( post-intervention ) , and 2.0 and 3.8 ( six-month post-intervention ) . CONCLUSION Data suggest that measurable learning outcomes were achieved . Residents receiving instruction improved and retained search ing skills six-months after intervention Background Previous studies have shown that Norwegian public health physicians do not systematic ally and explicitly use scientific evidence in their practice . They work in an environment that does not encourage the integration of this information in decision-making . In this study we investigate whether a theoretically grounded tailored intervention to diffuse evidence -based public health practice increases the physicians ' use of research information . Methods 148 self-selected public health physicians were r and omised to an intervention group ( n = 73 ) and a control group ( n = 75 ) . The intervention group received a multifaceted intervention while the control group received a letter declaring that they had access to library services . Baseline assessment s before the intervention and post-testing immediately at the end of a 1.5-year intervention period were conducted . The intervention was theoretically based and consisted of a workshop in evidence -based public health , a newsletter , access to a specially design ed information service , to relevant data bases , and to an electronic discussion list . The main outcome measure was behaviour as measured by the use of research in different documents . Results The intervention did not demonstrate any evidence of effects on the objective behaviour outcomes . We found , however , a statistical significant difference between the two groups for both knowledge scores : Mean difference of 0.4 ( 95 % CI : 0.2–0.6 ) in the score for knowledge about EBM-re sources and mean difference of 0.2 ( 95 % CI : 0.0–0.3 ) in the score for conceptual knowledge of importance for critical appraisal . There were no statistical significant differences in attitude- , self-efficacy- , decision-to-adopt- or job-satisfaction scales . There were no significant differences in Cochrane library search ing after controlling for baseline values and characteristics . Conclusion Though demonstrating effect on knowledge the study failed to provide support for the hypothesis that a theory-based multifaceted intervention targeted at identified barriers will change professional behaviour OBJECTIVE : To evaluate an educational intervention in evidence -based ethics ( emphasizing clinical knowledge , epidemiologic skills , and recognition of ethical issues ) administered to house staff before rotating through our neonatal intensive care unit . STUDY DESIGN : A controlled trial of 64 pediatric house staff assigned to alternating control and intervention rotations . Question naires were administered at the end of the rotation . RESULTS : Some benefits of the intervention were observed . However , a large percentage of intervention and control house staff substantially overestimated ( > 1.25 correct value ) predischarge mortality ( 23 % vs. 55 % of house staff ; p<0.02 ) , mortality or major morbidity ( 74 % vs. 46 % of house staff ; p=0.04 ) , and cerebral palsy rates ( 70 % vs. 87 % ; p=0.12 ) . Neither group cited many method ological criteria for evaluating follow-up studies ( 3.3 vs. 2.4 criteria ; p=0.05 ) or ethical issues considered in treatment recommendations for extremely premature infants ( 3.1 vs. 2.8 issues ; p=0.35 ) . CONCLUSION : Improved house staff training in evidence -based ethics is needed Objective An intervention existing of an evidence -based medicine ( EBM ) course in combination with case method learning sessions ( CMLSs ) was design ed to enhance the professional performance , self-efficacy and job satisfaction of occupational physicians . Methods A cluster r and omized controlled trial was set up and data were collected through question naires at baseline ( T0 ) , directly after the intervention ( T1 ) and 7 months after baseline ( T2 ) . The data of the intervention group [ T0 ( n = 49 ) , T1 ( n = 31 ) , T2 ( n = 29 ) ] and control group [ T0 ( n = 49 ) , T1 ( n = 28 ) , T2 ( n = 28 ) ] were analysed in mixed model analyses . Mean scores of the perceived value of the CMLS were calculated in the intervention group . Results The overall effect of the intervention over time comparing the intervention with the control group was statistically significant for professional performance ( p < 0.001 ) . Job satisfaction and self-efficacy changes were small and not statistically significant between the groups . The perceived value of the CMLS to gain new insights and to improve the quality of their performance increased with the number of sessions followed . Conclusion An EBM course in combination with case method learning sessions is perceived as valuable and offers evidence to enhance the professional performance of occupational physicians . However , it does not seem to influence their self-efficacy and job satisfaction Background To evaluate the educational effects of a clinical ly integrated e-learning course for teaching basic evidence -based medicine ( EBM ) among postgraduates compared to a traditional lecture-based course of equivalent content . Methods We conducted a cluster r and omised controlled trial in the Netherl and s and the UK involving postgraduate trainees in six obstetrics and gynaecology departments . Outcomes ( knowledge gain and change in attitude towards EBM ) were compared between the clinical ly integrated e-learning course ( intervention ) and the traditional lecture based course ( control ) . We measured change from pre- to post-intervention scores using a vali date d question naire assessing knowledge ( primary outcome ) and attitudes ( secondary outcome ) . Results There were six clusters involving teaching of 61 postgraduate trainees ( 28 in the intervention and 33 in the control group ) . The intervention group achieved slightly higher scores for knowledge gain compared to the control , but these results were not statistically significant ( difference in knowledge gain : 3.5 points , 95 % CI -2.7 to 9.8 , p = 0.27 ) . The attitudinal changes were similar for both groups . Conclusion A clinical ly integrated e-learning course was at least as effective as a traditional lecture based course and was well accepted . Being less costly than traditional teaching and allowing for more independent learning through material s that can be easily up date d , there is a place for incorporating e-learning into postgraduate EBM curricula that offer on-the-job training for just-in-time learning . Trial registration Trial registration number : ACTRN12609000022268 Summary Aim To evaluate the educational effectiveness of a clinical ly integrated e-learning course for teaching basic evidence -based medicine ( EBM ) among postgraduate medical trainees compared to a traditional lecture-based course of equivalent content . Methods We conducted a cluster r and omized controlled trial to compare a clinical ly integrated e-learning EBM course ( intervention ) to a lecture-based course ( control ) among postgraduate trainees at foundation or internship level in seven teaching hospitals in the UK West Midl and s region . Knowledge gain among participants was measured with a vali date d instrument using multiple choice questions . Change in knowledge was compared between groups taking into account the cluster design and adjusted for covariates at baseline using generalized estimating equations ( GEE ) model . Results There were seven clusters involving teaching of 237 trainees ( 122 in the intervention and 115 in the control group ) . The total number of postgraduate trainees who completed the course was 88 in the intervention group and 72 in the control group . After adjusting for baseline knowledge , there was no difference in the amount of improvement in knowledge of EBM between the two groups . The adjusted post course difference between the intervention group and the control group was only 0.1 scoring points ( 95 % CI −1.2–1.4 ) . Conclusion An e-learning course in EBM was as effective in improving knowledge as a st and ard lecture-based course . The benefits of an e-learning approach need to be considered when planning EBM curricula as it allows st and ardization of teaching material s and is a potential cost-effective alternative to st and ard lecture-based teaching Abstract Objective : To evaluate the READER model for critical reading by comparing it with a free appraisal , and to explore what factors influence different components of the model . Design : A r and omised controlled trial in which two groups of general practitioners assessed three papers from the general practice section of the BMJ . Setting : Northern Irel and . Subjects : 243 general practitioners . Main outcome measures : Scores given using the READER model ( Relevance , Education , Applicability , Discrimination , overall Evaluation ) and scores given using a free appraisal for scientific quality and an overall total . Results : The hierarchical order for the three papers was different for the two groups , according to the total scores . Participants using the READER method ( intervention group ) gave a significantly lower total score ( P⩽0.01 ) and a lower score for the scientific quality ( P⩽0.0001 ) for all three papers . Overall more than one in five ( 22 % ) , and more men than women , read more than 5 articles a month ( P⩽0.05 ) . Those who were trainers tended to read more articles ( P⩽0.05 ) , and no trainers admitted to reading none . Overall , 58 % ( 135/234 ) ( 68 % ( 76/112 ) of the intervention group ) believed that taking part in the exercise would encourage them to be more critical of published articles in the future ( P⩽0.01 ) . Conclusion : Participants using the READER model gave a consistently lower overall score and applied a more appropriate appraisal to the methodology of the studies . The method was both accurate and repeatable . No intrinsic factors influenced the scores , so the model is appropriate for use by all general practitioners regardless of their seniority , location , teaching or training experience , and the number of articles they read regularly BACKGROUND Evidence -based medicine requires new skills of physicians , including literature search ing . OBJECTIVE To determine which literature retrieving method is most effective for GPs : the printed Index Medicus ; Medline through Grateful Med ; or Medline on CD-ROM . METHODS The design was a r and omized comparative study . In a continuing medical education course , three groups of health care professionals ( 87 GPs and 16 other health care professionals ) used one of the literature retrieval methods to retrieve citations on four search topics related to general practice . For the analysis in pairs , we used the search results of the 75 participants who completed all four assignments . As outcome measures , we used precision , recall and an overall search quality score ; we also had a post-course question naire on personal characteristics , experience with computers , h and ling medical literature and satisfaction with course instruction and search results . RESULTS The recall and overall search quality scores in the Index Medicus groups ( n = 32 ) were higher ( P = < 0.001 ) than those in the CD-ROM groups ( n = 31 ) . In addition , the search quality scores in the Grateful Med groups ( n = 12 ) were higher ( P < 0.003 ) than those in the CD-ROM groups . There were no differences in precision . CONCLUSION In the period 1994 - 1997 , the printed Index Medicus was the most effective literature retrieval method for GPs . For inexperienced GPs , there is a need for training in electronic literature retrieval methods 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 OBJECTIVE To determine if a preceptor and individualized feedback improves the performance of physicians in search ing MEDLINE in clinical setting s. DESIGN R and omized controlled trial with 2 to 10 months follow-up . SETTING A 300-bed teaching hospital . PARTICIPANTS All 392 physicians and physicians-in-training from 6 major clinical departments were invited to participate if they made patient-care decisions during the study period ; 79.4 % agreed . INTERVENTIONS All participants were given 2 hours of basic training , then r and omized to a control group ( no further intervention ) or an intervention group in which each person chose a clinical preceptor experienced in MEDLINE search ing and received individualized feedback from a study librarian on each of their 1st 10 search es . MAIN OUTCOME MEASURES The number and proportion of relevant and irrelevant references retrieved for 1st , 4th , and 8th search es of participants were compared with independent librarian search es on the same topics . RESULTS Intervention group members did not search more often than controls ( 5.9 search es per month versus 4.7 , respectively ; P = 0.26 ) and there were no significant differences in the quality of search es . Rather , search performance for both groups improved , with the average number of relevant references retrieved per search increasing from 4.5 to 7.4 ( P < 0.01 ) . The librarian retrieved more relevant citations than participants for the 1st search ( P = 0.001 ) but not for the 4th ( P = 0.60 ) or 8th ( P = 0.76 ) search es . CONCLUSIONS A program of assigning preceptors and providing feedback on individual search es did not enhance the quantity or quality of search es . Soon after a basic introduction to search ing , however , clinicians in both groups improved their search performance Introduction Critical appraisal skills are believed to play a central role in an evidence -based approach to health practice . The aim of this study was to evaluate the effectiveness and costs of a critical appraisal skills educational intervention aim ed at health care professionals . Methods This prospect i ve controlled trial r and omized 145 self-selected general practitioners , hospital physicians , professions allied to medicine , and healthcare managers/administrators from the South West of Engl and to a half-day critical appraisal skills training workshop ( based on the model of problem-based small group learning ) or waiting list control . The following outcomes were assessed at 6-months follow up : knowledge of the principles necessary for appraising evidence ; attitudes towards the use of evidence about healthcare ; evidence seeking behaviour ; perceived confidence in appraising evidence ; and ability to critically appraise a systematic review article . Results At follow up overall knowledge score [ mean difference : 2.6 ( 95 % CI : 0.6 to 4.6 ) ] and ability to appraise the results of a systematic review [ mean difference : 1.2 ( 95 % CI : 0.01 to 2.4 ) ] were higher in the critical skills training group compared to control . No statistical significant differences in overall attitude towards evidence , evidence seeking behaviour , perceived confidence , and other areas of critical appraisal skills ability ( methodology or generalizability ) were observed between groups . Taking into account the workshop provision costs and costs of participants time and expenses of participants , the average cost of providing the critical appraisal workshops was approximately £ 250 per person . Conclusions The findings of this study challenge the policy of funding ' one-off ' educational interventions aim ed at enhancing the evidence -based practice of health care professionals . Future evaluations of evidence -based practice interventions need to take in account this trial 's negative findings and method ological difficulties Background Evidence -based medicine ( EBM ) has been widely integrated into residency curricula , although results of r and omized controlled trials and long term outcomes of EBM educational interventions are lacking . We sought to determine if an EBM workshop improved internal medicine residents ' EBM knowledge and skills and use of secondary evidence re sources . Methods This r and omized controlled trial included 48 internal medicine residents at an academic medical center . Twenty-three residents were r and omized to attend a 4-hour interactive workshop in their PGY-2 year . All residents completed a 25-item EBM knowledge and skills test and a self-reported survey of literature search ing and re source usage in their PGY-1 , PGY-2 , and PGY-3 years . Results There was no difference in mean EBM test scores between the workshop and control groups at PGY-2 or PGY-3 . However , mean EBM test scores significantly increased over time for both groups in PGY-2 and PGY-3 . Literature search es , and re source usage also increased significantly in both groups after the PGY-1 year . Conclusions We were unable to detect a difference in EBM knowledge between residents who did and did not participate in our workshop . Significant improvement over time in EBM scores , however , suggests EBM skills were learned during residency . Future rigorous studies should determine the best methods for improving residents ' EBM skills as well as their ability to apply evidence during clinical practice Background As the overall evidence for the effectiveness of teaching of evidence based medicine ( EBM ) is not strong , and the impact of cultural and societal influences on teaching method is poorly understood , we undertook a r and omised-controlled trial to test the effectiveness and learning satisfaction with two different EBM teaching methods ( usual teaching vs. problem based learning ( PBL ) ) for undergraduate medical students . Methods A mixed methods study that included a r and omised-controlled crossover trial with two intervention arms ( usual teaching and PBL ) and a nested qualitative study with focus groups to explore student perceptions of learning and to assess the effectiveness and utility of the two teaching methods .All 129 second-year medical students at the University of Hong Kong in 2007.The main outcomes measures were attitudes towards EBM ; personal application and current use of EBM ; EBM knowledge ; future use of EBM . Results PBL was less effective at imparting knowledge than usual teaching consisting of a lecture followed by a group tutorial . After usual teaching students showed improvement in scores for ' attitudes towards EBM ' , ' personal application and current use of EBM ' and ' EBM knowledge , which were not evident after PBL . In contrast to the usual teaching , students found PBL difficult as they lacked the statistical knowledge necessary to support discussion , failed to underst and core concepts , and lost direction . Conclusion The evidence presented here would suggest that the teaching of EBM within an Asian environment should adopt a format that facilitates both the acquisition of knowledge and encourages enquiry Background Prior educational interventions to increase seeking evidence by medical students have been unsuccessful . Methods We report two quasir and omized controlled trials to increase seeking of medical evidence by third-year medical students . In the first trial ( 1997–1998 ) , we placed computers in clinical locations and taught their use in a 6-hour course . Based on negative results , we created SUM Search ( TM ) , an Internet site that automates search ing for medical evidence by simultaneous meta- search ing of MEDLINE and other sites . In the second trial ( 1999–2000 ) , we taught SUM Search 's use in a 5½-hour course . Both courses were taught during the medicine clerkship . For each trial , we surveyed the entire third-year class at 6 months , after half of the students had taken the course ( intervention group ) . The students who had not received the intervention were the control group . We measured self-report of search frequency and satisfaction with search quality and speed . Results The proportion of all students who reported search ing at least weekly for medical evidence significantly increased from 19 % ( 1997–1998 ) to 42 % ( 1999–2000 ) . The proportion of all students who were satisfied with their search results increased significantly between study years . However , in neither study year did the interventions increase search ing or satisfaction with results . Satisfaction with the speed of search ing was 27 % in 1999–2000 . This did not increase between studies years and was not changed by the interventions . Conclusion None of our interventions affected search ing habits . Even with automated search ing , students report low satisfaction with search speed . We are concerned that students using current strategies for seeking medical evidence will be less likely to seek and appraise original studies when they enter medical practice and have less time Background The specificity of clinical questions is gauged by explicit descriptions of four dimensions : subjects , interventions , comparators and outcomes of interest . This study determined whether adding simple instructions and examples on clinical question formulation would increase the specificity of the su bmi tted question compared to using a st and ard form without instructions and examples . Methods A r and omised controlled trial was conducted in an evidence - search and appraisal service . New participants were invited to reformulate clinical queries . The Control Group was given no instructions . The Intervention Group was given a brief explanation of proper formulation , written instructions , and diagrammatic examples . The primary outcome was the change in the proportion of reformulated questions that described each the dimensions of specificity . Results Fifty-two subjects agreed to participate in the trial of which 13 were lost to follow-up . The remaining 17 Intervention Group and 22 Control Group participants were analysed . Baseline characteristics were comparable . Overall , 20 % of initially su bmi tted questions from both groups were properly specified ( defined as an explicit statement describing all dimensions of specificity ) . On follow-up , 7/14 questions previously rated as mis-specified in the Intervention Group had all dimensions described at follow-up ( p = 0.008 ) while the Control Group did not show any changes from baseline . Participants in the Intervention Group were also more likely to explicitly describe patients ( p = 0.028 ) , comparisons ( p = 0.014 ) , and outcomes ( p = 0.008 ) . Conclusions This trial demonstrated the positive impact of specific instructions on the proportion of properly-specified clinical queries . The evaluation of the long-term impact of such changes is an area of continued research Objective : To teach internal medicine residents key principles of clinical epidemiology that are necessary to read critically the medical literature . Design : Two-phase , non-r and omized , controlled educational trial . Setting : University-based training program for residents ( PGY-l-PGY-3 ) in internal medicine . Participants : All 83 residents participated in the trial . Seventy residents completed a test in clinical epidemiology at the end of Phases I and II . Interventions : Residents were assigned to one of eight ambulatory care clinics for half a day each week . A literature -based curriculum in critical appraisal was the subject of a weekly pre-clinic conference for four clinics ( Group A ) . The other four clinics ( Group B ) had a weekly conference on topics in ambulatory care medicine . At the end of Phase I , both groups were given a test of basic knowledge of clinical epidemiology . The curriculum was then modified with the addition of written questions to emphasize important educational points and to stimulate resident participation . The modified curriculum became the subject of the preclinic conference for Group B , while Group A changed to topics in ambulatory medicine . At the end of Phase II both groups were again tested on basic knowledge of clinical epidemiology . Results : Group B performed significantly better on the second test than on the first , 68.5 % vs. 63.3 % ( p=0.034 ) , while Group A did not improve ( 64.5 % vs. 65.9 % ) . The differences in test scores for Test II minus Test I were+5.17 % in Group B and −1.44 % in Group A ( p=0.019 ) . Twenty-one percent of Group B residents vs. 5 % of Group A residents improved their scores by 18 % or more . Conclusions : The residency period is a difficult but important time to teach critical appraisal skills . Educational gains may be small and need to be critically evaluated to stimulate the development of more effective educational programs A double-blind r and omised controlled trial was conducted on a group of Hong Kong hospital clinicians . The objective was to test if a three-hour educational workshop ( with supervised h and s-on practice ) is more effective ( than no training ) to improve clinical question formulation , information-seeking skills , knowledge , attitudes , and search outcomes . The design was a post-test-only control group ; recruitment by stratified r and omization ( by profession ) , blocked at 800 . End-user training was more effective than no training in improving clinical question formulation , in raising awareness , knowledge , confidence and use of data bases , but had made no impact on preference for secondary data bases . It changed the attitude of clinicians to become more positive towards the use of electronic information services ( EIS ) . Participants had higher search performance and outcomes ( satisfaction with information obtained ( NNT = 3 ) , EIS satisfaction ( NNT = 3 ) and success in problem solving ( NNT = 4 ) ) . The workshop improved knowledge and skills in evidence -based search ing , but this effect gradually eroded with time . Search logs confirmed that follow-up is required if effects are to be sustained . Longer effects on search behaviours appear to be positive . A r and omised controlled trial is valuable in identifying cause- and -effect relations and to quantify the magnitude of the effects for management decision-making 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 Purpose . To measure the impact of a resident focused evidence -based medicine ( EBM ) educational intervention on EBM knowledge of residents and students , to assess its feasibility , and to evaluate residents ’ attitudes regarding this rotation . Method . In 2002 , based on the EBM user and EBM practitioner model , the authors design ed the EBM elective rotation and conducted a controlled trial of its implementation in the internal medicine residency program in three teaching hospitals affiliated with the University at Buffalo , New York . The intervention group ( one hospital , 17 medical students and residents ) received a multifaceted intervention . In the control group ( two hospitals , 23 medical students and residents ) , there was no curriculum change . The effectiveness in a pre- and posttest was assessed using the English version of the Berlin Question naire . A survey of all internal medicine residents ( n = 119 ) was conducted to evaluate their attitudes toward the EBM elective rotation . Results . In the intervention group , knowledge improved slightly , but not significantly ( .71 on a scale ranging from 0–15 on the Berlin question naire , p = .3 ) . The mean score in the control group decreased significantly ( 1.65 , p = .005 ) . The difference in change scores between the two groups was significant even after adjustment for covariates ( 2.52 , p = .006 ) . Residents ( response rate 83 % ) had positive attitudes regarding the rotation . Conclusion . An EBM elective rotation was successfully integrated into a residency program . This multifaceted educational approach with an “ on-the-ward ” EBM resident , may improve the EBM knowledge and skills of targeted students and residents Objective : Does MEDLINE use , when added to more traditional sources of information , improve the accuracy of medical students ' clinical decisions when compared to those obtained using traditional sources only ? Design : R and omized control trial . Setting : McMaster University Faculty of Medicine , Undergraduate Program . Participants : The entire class of 101 medical students , class of 1998 . Overall response rate on 9items was 56 % ( 510/909 ) , with 35 % ( 35/101 ) completing all 9 items . Intervention : All participants were r and omized on each of the nine clincal scenarios for which the student could choose to apply , or refrain from applying , a proferred intervention . When r and omized to the control arm , the student used traditional sources of information for decision-making . When r and omized to the experimental arm , the student used MEDLINE search ing in addition to more traditional sources of information , for decision-making . Main Outcome Measures : Prior to , and subsequent to the information search , the students indicated their comfort in using the proffered intervention on a seven point Likert scale . Results : Analyzed with one-way ANOVA , the mean rating post- search of the control non- MEDLINE arm was2.94 ( SD = 1.80 ) ( where 1 = correct , 7 = incorrect ) and of the experimental MEDLINE arm was 2.71 ( SD = 1.81 ) , ( F(1,522 ) = 2.03 , p = 0.15 n.s ) . The mean change of the control arm was 0.97 ( SD = 2.04 ) and of the experimental arm was 1.008 ( SD = 1.92 ) , ( F(1,511 ) = 0.04,p = 0.84n.s . ) . Conclusions : The addition of MEDLINE to more traditional answer-seeking behaviors by medical students does not translate into a beneficial impact on clinical decision-making RATIONALE The concept of evidence -based practice ( EBP ) encourages health care professionals to provide the most effective health care , and to be accountable for the interventions they provide . Little work has been undertaken to examine how practically allied health professionals ' encompass EBP and how they perceptive and underst and the concept of EBP . The use of opinion leaders to disseminate new evidence into practice , and thereby encourage the behaviour of health care professionals has been proposed . AIMS The aims of this study were to investigate physiotherapists ' attitudes towards EBP and to examine change in their attitudes following an education package , which utilized local opinion leaders . METHOD Thirty musculoskeletal physiotherapists from a Community Trust in North Staffordshire were cluster r and omized by location of work to two groups . The intervention group received an evidence -based programme on aspects of EBP including literature search ing and critical appraisal . The attention control group received a st and ard in-service training package on the management of common knee pathologies . The physiotherapists ' attitudes towards EBP were measured at baseline ( before r and omization ) and at 3 and 6 months follow-up . RESULTS Physiotherapists reported that they primarily relied on ' courses ' and ' in-service training ' for informing their clinical practice . Most agreed that clinical practice should be based on the best available evidence and that they would change their clinical practice if evidence suggested they should do so . However , many of the physiotherapists reported difficulty in reading journals and could not identify opinion leaders in key areas . In terms of clinical practice , literature , journals and research were ascribed low priority throughout . Differences in attitudes between the intervention and control groups were observed in relation to management support for EBP at 3 and 6 months follow-up . CONCLUSIONS In this study , physiotherapists appeared to be in favour of the idea of EBP , yet they remained reluctant to change their practice . Opinion leaders were not easily identifiable by physiotherapists , suggesting that this method alone may not be an effective method of changing attitudes in clinical practice . The process of changing attitudes in the clinical environment is a complex issue worthy of further research Objective : To determine whether an interactive seminar could affect medical student knowledge of research design , basic critical appraisal skills , and attitudes toward and clinical use of the medical literature . Design : Controlled , nonr and omized clinical trial Participants : Third-year clinical clerks ( n=146 ) during their core medicine clerkship . Interventions : Two 90 minute interactive seminars . Measurements and main results : Pre- and post question naires were used to assess knowledge and attitudes regarding the use of the medical literature among 65 study and 81 control students . Blinded review of write-ups assessed actual use of the medical literature . Overall , 80 % of the students subscribed to one or more journals and reported reading three or more journal articles per month . After the intervention , the study students were more likely than the control students to consider : 1 ) study design important in article selection and 2 ) use of medical literature critical to patient care decisions . Knowledge scores were significantly improved in the study group ( p=0.0001 ) . The intervention yielded no increase in the actual use of medical literature in patient write-ups over that encouraged by usual clerkship goals . 51 % of the study and 48 % of the control students cited literature at baseline , and 53 % of all the students did so after the intervention . Of these citations , 50 % were for journal articles and the remainder were for textbooks . The students infrequently mentioned the quality of the cited literature . Conclusions : An interactive seminar design ed to introduce medical students to critical appraisal improved student knowledge and attitudes but did not increase the actual use of literature in patient writeups BACKGROUND Evidence Based Review s in Surgery ( EBRS ) is an Internet journal club that is effective in teaching critical appraisal skills to practicing surgeons . The objective of this r and omized controlled trial was to determine whether teaching critical appraisal skills to surgical residents through the Internet is as effective as a moderated in-person journal club . STUDY DESIGN Twelve general surgery programs were cluster-r and omized to an Internet group ( 6 programs ; 227 residents ; 23 to 47 residents/program ) or a moderated journal club ( 6 programs , 216 residents , 21 to 72 residents/program ) . Each EBRS package includes a clinical and method ological article plus clinical and method ological review s. Residents in the Internet group were required to complete 8 EBRS packages online plus participate in an online discussion group . Residents in the moderated group were required to attend 8 journal clubs moderated by a faculty member . All residents completed a vali date d test assessing expertise in critical appraisal . RESULTS In the Internet group , only 18 % of residents completed at least 1 EBRS package compared with 96 % in the moderated group . One hundred and thirty ( 57.8 % ) residents in the Internet group completed the test compared with 157 ( 72.7 % ) in the moderated group . The residents in the moderated group scored considerably better on the critical appraisal test , with a mean score of 42.1 compared with 37.4 in the Internet group ( p = 0.05 ) , with a moderate effect size of 0.6 SD . CONCLUSIONS A moderated journal club is considerably better in teaching critical appraisal skills to surgical residents . This is likely because of the low participation in the Internet journal club OBJECTIVES To measure the effectiveness of an educational intervention design ed to teach residents four essential evidence -based medicine ( EBM ) skills : question formulation , literature search ing , underst and ing quantitative outcomes , and critical appraisal . DESIGN Firm-based , controlled trial . SETTING Urban public hospital . PARTICIPANTS Fifty-five first-year internal medicine residents : 18 in the experimental group and 37 in the control group . INTERVENTION An EBM course , taught 2 hours per week for 7 consecutive weeks by senior faculty and chief residents focusing on the four essential EBM skills . MEASUREMENTS AND MAIN RESULTS The main outcome measure was performance on an EBM skills test that was administered four times over 11 months : at baseline and at three time points postcourse . Postcourse test 1 assessed the effectiveness of the intervention in the experimental group ( primary outcome ] ; postcourse test 2 assessed the control group after it crossed over to receive the intervention ; and postcourse test 3 assessed durability . Baseline EBM skills were similar in the two groups . After receiving the EBM course , the experimental group achieved significantly higher postcourse test scores ( adjusted mean difference , 21 % ; 95 % confidence interval , 13 % to 28 % ; P < .001 ) . Postcourse improvements were noted in three of the four EBM skill domains ( formulating questions , search ing , and quantitative underst and ing [ P < .005 for all ] , but not in critical appraisal skills [ P = .4 ] ) . After crossing over to receive the educational intervention , the control group achieved similar improvements . Both groups sustained these improvements over 6 to 9 months of follow-up . CONCLUSIONS A brief structured educational intervention produced substantial and durable improvements in residents ' cognitive and technical EBM skills BACKGROUND The effectiveness of interventions for developing critical appraisal skills in practicing physicians has not been studied , despite the documented importance of reading the literature in caring for patients and in continuing professional development . The objective of this study was to evaluate whether an Internet-based intervention would lead to enhanced critical appraisal skills in practicing surgeons . METHODS General surgeons who agreed to participate were r and omized into 2 groups . The intervention was a curriculum in critical appraisal skills that included a clinical and method ologic article , a listserve discussion , and clinical and method ologic critiques . The control group received only the clinical articles . The primary outcome measure was a previously vali date d 2-hour test of critical appraisal . RESULTS Of the 55 surgeons who completed the examination , subjects in the intervention group performed better on the test of critical appraisal skills than those in the control group ( mean score : intervention group , 58 % + /- 8 vs control group , 50 % + /- 8) , with a large effect size of 1.06 st and ard deviation units ( t+3.92 , P < .0001 ) . Training conditions accounted for 22 % of the variance in total scores . CONCLUSIONS A multifaceted , Internet-based intervention result ed in improved critical appraisal skills of practicing general surgeons Purpose Many educational programs seek to develop skills in evidence -based medicine ( EBM ) . The authors examined the efficacy of teaching the EBM skill of efficiently search ing the research literature . They compared students who received brief training in EBM search ing skills with those who did not , and assessed the quality of literature search ing one month after that training . Method The authors used a nonr and omized control group study design to quantify the impact of a single , brief ( two-hour ) instructional intervention on EBM-based techniques for search ing Medline for evidence related to a clinical problem provided to the students . Ninety-two fourth-year medical students ( 34 intervention , 58 control ) at the University of Michigan participated in a four-week EBM elective between 2001 and 2003 . The authors conducted a preintervention assessment of search ing skills , followed by a repeat assessment one month after the intervention . Search quality was judged by medical librarians using a structured clinical scenario and scoring algorithm . Results Data for 30 intervention and 40 control students could be analyzed . Intervention students had fewer search errors and correspondingly higher quality search es than did control students . The educational intervention accounted for approximately 8 % of the variance in both of these outcomes . The most common search errors were a lack of Medical Subject Headings ( MeSH ) explosion , missing MeSH terms , lack of appropriate limits , failure to search for best evidence , and inappropriate combination of all search concepts . Conclusions This study provides evidence that a single , brief training session can have a marked beneficial effect on the quality of subsequent , short-term EBM literature search ing performance outcomes RATIONALE , AIMS AND OBJECTIVES Traditional continuing medical education programmes that offer passive learning have been shown to be poorly effective at changing doctors ' clinical behaviour . A multifaceted evidence -based medicine ( EBM ) intervention was conducted at the largest health maintenance organization ( HMO ) in Israel , attempting to facilitate a change in doctors ' attitudes , knowledge and clinical behaviour . No study thus far has examined the association between the teaching of EBM principles and doctors ' clinical behaviour . This study evaluated the intervention programme through a controlled trial and before and after study . The objective of the evaluation is binary : first , to examine the impact of an educational intervention on family doctors ' test ordering performance and drug utilization by their patients ; and second , to assess the impact of the intervention on attitudes towards evidence -based practice and knowledge . METHODS Controlled trial and before and after study . Primary care clinics comprising similar patient characteristics were r and omly allocated to the experimental or to the control group . Doctors in the experimental group participated in an EBM educational intervention , while the control group did not take part in the intervention . Clinicians ' test ordering performance and their patients ' drug utilization were derived from the HMO 's data base before intervention , after workshops and after intervention . Participants in the controlled trial consisted of 75 doctors and their 106 349 patients . The before and after study evaluated intervention doctors ' ( n = 70 ) EBM attitudes and knowledge through a vali date d question naire before and after workshops . RESULTS EBM workshops enhanced intervention doctors ' EBM knowledge scores from 22.4/100 before workshops to 40.8/100 after workshops ( P = 0.000 ) . Doctors improved their ability to formulate clinical questions while enhancing their search strategy using Medline . In a linear regression model , two covariates , specialization ( B = 12.59 ; P = 0.001 ) and habitually reading medical journals ( B = 6.45 ; P = 0.052 ) , best explained the variance in doctors ' EBM knowledge scores , while controlling for pre-intervention scores ( R(2 ) = 0.569 ; P = 0.000 ) . Results from the controlled trial indicated that no statistically significant differences were found between intervention and control doctors ' test ordering performances , and their patients ' drug utilization . CONCLUSIONS The results of the study suggest that the intervention positively influenced attitudes and knowledge ; however , no statistically significant impact was found on doctors ' test ordering performance and on their patients ' drug utilization . The intervention 's inability to change doctors ' clinical behaviour might be remedied by improving future interventions through adding additional facets to the educational intervention , such as social marketing techniques and personal feedback . A longer and more extensive intervention might be more effective but is extremely difficult to execute as we found in this study . Future larger-scale interventions must incorporate the intervention into the routines of the organization , thus minimizing barriers towards EBM implementation BACKGROUND Considerable barriers still prevent paediatricians from successfully using information retrieval technology . OBJECTIVES To verify whether the assistance of biomedical librarians significantly improves the outcomes of search es performed by paediatricians in biomedical data bases using real-life clinical scenarios . METHODS In a controlled trial at a paediatric teaching hospital , nine residents and interns were r and omly allocated to an assisted search group and nine to a non-assisted ( control ) group . Each participant search ed PubMed and other online sources , performing pre-determined tasks including the formulation of a clinical question , retrieval and selection of bibliographic records . In the assisted group , participants were supported by a librarian with ≥5 years of experience . The primary outcome was the success of search sessions , scored against a specific assessment tool . RESULTS The median score of the assisted group was 73.6 points interquartile range ( IQR = 13.4 ) vs. 50.4 ( IQR = 17.1 ) of the control group . The difference between median values in the results was 23.2 points ( 95 % CI 4.8 - 33.2 ) , in favour of the assisted group ( P-value , Mann-Whitney U test : 0.013 ) . CONCLUSIONS The study has found quantitative evidence of a significant difference in search performance between paediatric residents or interns assisted by a librarian and those search ing the literature alone Background To practice Evidence -Based Medicine ( EBM ) , physicians must quickly retrieve evidence to inform medical decisions . Internal Medicine ( IM ) residents receive little formal education in electronic data base search ing , and have identified poor search ing skills as a barrier to practicing EBM . Objective To design and implement a data base search ing tutorial for IM residents on inpatient rotations and to evaluate its impact on residents ’ skill and comfort search ing MEDLINE and filtered EBM re sources . Design R and omized controlled trial . Residents r and omized to the search ing tutorial met for up to 6 1-hour small group sessions to search for answers to questions about current hospitalized patients . Participants Second- and 3rd-year IM residents . Measurements Residents in both groups completed an Objective Structured Search ing Evaluation ( OSSE ) , search ing for primary evidence to answer 5 clinical questions . OSSE outcomes were the number of successful search es , search times , and techniques utilized . Participants also completed self- assessment surveys measuring frequency and comfort using EBM data bases . Results During the OSSE , residents who participated in the intervention utilized more search ing techniques overall ( p < .01 ) and used PubMed ’s Clinical Queries more often ( p < .001 ) than control residents . Search ing “ success ” and time per completed search did not differ between groups . Compared with controls , intervention residents reported greater comfort using MEDLINE ( p < .05 ) and the Cochrane Library ( p < .05 ) on post-intervention surveys . The groups did not differ in comfort using ACP Journal Club , or in self-reported frequency of use of any data bases . Conclusions An inpatient EBM search ing tutorial improved search ing techniques of IM residents and result ed in increased comfort with MEDLINE and the Cochrane Library , but did not impact overall search ing success Over the past decade , on-line data bases have become increasingly popular among health care professionals . As a group , these ' end-users ' report utilizing data bases to keep abreast of medical progress , to conduct research and to address specific patient care issues . Throughout the literature , medical professionals ( ' content experts ' ) have proved to be less effective search ers than librarians ( ' search experts ' ) . The potential implication s of this discrepancy are worrysome . For any given clinical scenario , for example , published reports may reach contradictory conclusions . A poorly skilled search er may not retrieve enough articles to appreciate this fact . Optimizing search ing skills is therefore a worthwhile goal . As a first step , many medical schools introduce students to on-line data bases , most notably MEDLINE . Residency is an ideal time to continue this training . A recognized obstacle to provide residents with formal MEDLINE instruction is time constraint . We therefore conducted this study to ascertain the impact an individual 1-hour tutorial session would have on MEDLINE utilization among obstetrics and gynecology residents training at an academic medical centre . Outcome measures included MEDLINE search frequency , duration , recall , precision and search er satisfaction . Search recall measures the search er 's ability to retrieve articles deemed relevant to the question at h and . Search precision gauges the search ers ' ability to eliminate irrelevant articles . Although the sessions were well received , we were unable to demonstrate an improvement in the outcome measures analysed . Further research is therefore indicated so that cost-effective educational strategies can be recommended for wide-scale use R and omized , controlled trials ( RCTs ) of herbal interventions often inadequately describe important aspects of their methods ( 1 - 4 ) . Although the quality of reporting of these trials may be improving with time , many still lack important information , particularly about the composition of the herbal intervention ( 4 , 5 ) . Crude herbal drugs are natural products and their chemical composition varies depending on several factors , such as geographic source of the plant material , climate in which it was grown , and time of harvest . Commercially available herbal medicinal products also vary in their content and concentration of chemical constituents from batch to batch and when products containing the same herbal ingredient are compared among manufacturers ( 6 - 14 ) . Even when herbal products are st and ardized for content of known active or marker compounds to achieve more consistent pharmaceutical quality , there is variation in the concentrations of other constituents . These variations can result in differences in pharmacologic activity in vitro ( 15 ) and in bioavailability in humans ( 16 ) . Mindful of these issues , we elaborated on the 22-item checklist of the Consoli date d St and ards of Reporting Trials ( CONSORT ) statement ( 17 ) to help authors and editors improve reporting of RCTs of herbal interventions . Methods We developed these reporting recommendations in 3 phases that included premeeting item generation , a consensus meeting , and postmeeting feedback . The individuals who participated are listed in the Appendix . To generate items , 1 investigator conducted telephone interviews of 16 participants with expertise in the method and reporting of RCTs ( 5 participants ) , pharmacognosy ( 4 participants ) , herbal medicinal products ( 5 participants ) , medical statistics ( 1 participant ) , and herbal product manufacturing ( 1 participant ) . The investigator asked participants to suggest revisions to existing CONSORT checklist items and also to additional items required for reporting trials of herbal interventions . He asked participants to nominate revisions or new items on the basis of empirical evidence that not reporting the item would bias estimates of treatment effect . When no empirical evidence was available , commonsense reasoning was acceptable . After completing all telephone calls , the investigator thematically grouped items and circulated them by e-mail to each participant for review . Fourteen participants attended the consensus meeting . The meeting began with a review of the premeeting checklist item suggestions . We emphasized minimizing item elaborations and additions and basing elaborations on evidence whenever possible . Each item suggestion was presented and followed by debate for its inclusion , deletion , or modification . This process was repeated until all items were review ed and a consensus emerged . After the consensus meeting , we circulated a draft summary report to all participants to ensure that it accurately represented decisions made during the consensus meeting . We then circulated the report to the wider CONSORT Group for input and revised it on the basis of their suggestions . Ethical approval was obtained from The University of Toronto Health Sciences Ethics Review Committee on 23 January 2004 . Financial support for the consensus meeting was provided by the Canadian Institutes of Health Research . The funding body had no role in the design , conduct , or analysis of this study and did not influence the decision to su bmi t the manuscript for publication . All research ers are independent of the funders . Results The group did not recommend any new CONSORT checklist items or modifications in the CONSORT flow diagram . We did , however , elaborate on 9 of the 22 CONSORT checklist items to enhance their relevance to trials of herbal interventions ( Table , Figure ; Appendix Table ) , including minor recommendations for 8 items ( item 1 [ title and abstract ] , item 2 [ background ] , item 3 [ participants ] , item 6 [ outcomes ] , item 15 [ baseline data ] , item 20 [ interpretation ] , item 21 [ generalizability ] , and item 22 [ overall evidence ] ) and detailed recommendations for 1 item ( item 4 [ interventions ] ) . Table . Proposed Elaboration of CONSORT Checklist Item 4 for Reporting R and omized , Controlled Trials of Herbal Medicine Interventions Figure . The high-pressure liquid chromatography chemical fingerprint for the extract of Ginkgo biloba L Appendix Table . Proposed Elaborations of CONSORT Items for R and omized , Controlled Trials of Herbal Medicine Interventions The Table shows the detailed recommendations for item 4 and an example of good reporting related to each recommendation . These recommendations begin with the words where applicable to indicate that all information suggested may not be applicable to every type of herbal medicine intervention . For example , an herbal medicinal product comprising crude herbal material ( for example , leaves and stems ) simply prepared as a tea or decoction does not require description of the type and concentration of solvent used and the ratio of herbal drug to extract ( item 4B.3 ) . Also , not every herbal medicine intervention will have a finished product or extract name or manufacturer ( item 4A.2 ) , but instead may be made by the investigators specifically for the study . In such circumstances , all methods used in preparing and formulating the product must be reported . Similarly , item 4F is not required for herbal interventions when the practitioner is not a part of the intervention . With these exceptions , we recommend that all information shown in the Table be reported for all herbal interventions . Discussion We developed recommendations to be used in conjunction with the existing CONSORT checklist when reporting RCTs of herbal interventions . In particular , we thought it imperative that reports of RCTs provide clear and complete descriptions of the herbal intervention . We think that our recommendations might also be relevant for reporting herbal interventions in other research design s , whether pre clinical ( for example , in vivo or in vitro ) or clinical ( for example , N of 1 trials ) , and refer interested readers to a detailed explanatory document that further describes each of our recommendations and provides additional examples of good reporting ( 22 ) . We hope that authors find our recommendations instructive and that journals will endorse their use and modify their instructions to authors accordingly Medical students taking a course in epidemiology for clinical practice were taught by either lectures , small group seminars or self-learning packages . Examination performances were no different for the three groups , but self-perceived mastery of learning objectives , and satisfaction with the course were higher for students who received self-learning packages . Sixty per cent of self instruction students found the teaching method was successful compared with 37 % of the seminar students and only 19 % who received lectures . A combination of self-instructional package and seminar would seem to hold most promise for a workable and effective course PURPOSE To test whether an academic detailing intervention would improve journal reading among residents . METHOD In 1995 - 96 , the authors conducted a r and omized controlled trial at two family medicine residencies in Missouri . Fifty-nine family practice residents were r and omized into two groups identical in baseline characteristics ; 29 received individual 15-minute educational presentations , based on academic detailing , that emphasized careful selection of medical journal articles for reading . The authors measured the percentage of important journal articles of which the residents were aware , the percentage of those they had read ( either abstract only or the whole article ) , and the percentage of correctly answered knowledge questions . RESULTS Despite r and omization , the residents in the control group indicated on the pretest that they were more likely than were the residents in the intervention group to be aware of and to have read abstract s from selected articles . However , when comparing pretest with posttest results , the intervention group recalled 18.2 % ( 95 % CI , 2.0 , 34.0 ) more articles and correctly answered 16.6 % ( 95 % CI 3.0 , 29.9 ) more knowledge questions than did the control group . CONCLUSION A brief intervention increased residents ' recall of important articles and knowledge of those articles ' conclusions OBJECTIVES To compare 2 educational programmes for teaching evidence -based medicine ( EBM ) . DESIGN Prospect i ve r and omised controlled trial accompanied by a qualitative evaluation . SETTING University of Oslo , Norway , 2002 - 03 . PARTICIPANTS A total of 175 students entered the study . All tenth semester medical students from 3 semesters were eligible for inclusion if they completed baseline assessment and consent forms and either attended teaching on the first day of the semester or gave reasons for their absence on the first day in advance . Interventions One intervention was based on computer-assisted , self-directed learning ( self-directed intervention ) , whilst the other was organised as workshops based on social learning theory ( directed intervention ) . Both educational interventions consisted of 5 half-day sessions . MAIN OUTCOME MEASURES The primary outcomes were knowledge about EBM and skills in critical appraisal . A secondary outcome measured attitudes to EBM . Outcomes were compared on an intention-to-treat basis using a stratified Wilcoxon rank-sum test . RESULTS There were no differences in outcomes for the 2 study groups in terms of EBM knowledge ( mean deviation 0.0 [ 95 % confidence interval - 1.0 , 1.0 ] , P = 0.8 ) , critical appraisal skills ( MD 0.1 [ 95 % CI - 0.9 , 1.1 ] , P = 0.5 ) , or attitudes to EBM ( MD - 0.3 [ 95 % CI - 1.4 , 0.8 ] , P = 0.5 ) . Follow-up rates were 96 % , 97 % and 63 % , respectively . CONCLUSIONS This trial and its accompanying qualitative evaluation suggest that self-directed , computer-assisted learning may be an alternative format for teaching EBM . However , further research is needed to confirm this and investigate alternative educational models BACKGROUND Critical reading is an important skill for those trying to practice evidence -based medicine . There are a number of recognized structures for critical reading , including the READER model . These methods should be subjected to high- quality studies . OBJECTIVES We aim ed to evaluate the READER method in a practical teaching setting using the highest quality research methodology . METHODS We carried out a modified r and omized controlled trial . Two groups of GP trainers were invited to appraise critically the two articles using either the READER acronym or a semi-structured free appraisal . RESULTS Of 99 participants in the workshop , 92 completed the study . One-third of participants ( 33.7 % ) read more than five articles per month and those who had been in practice the longest read fewer articles ( P<0.05 ) . Both groups attributed the lowest score to paper 2 . The median total scores were higher using the READER method , although only significant for paper 2 ( P<0.05 ) . The median score attributed to the methodology was lower using the READER method than the free appraisal , although this difference was only significant for paper 1 ( P<0.05 ) . Overall , 51 % ( 70 % of the READER group ) believed that taking part in the exercise would encourage them to be more critical of published articles in the future . CONCLUSION Those using the READER method attributed a higher total score , but were more critical of the methodology than those using a free appraisal . Participants found the study useful and believed that it would be of help in future critical appraisal . The study raises interesting questions about the relative importance to GPs of method ological rigour compared with other factors when evaluating research papers Background Evidence -based medicine ( EBM ) is widely taught in residency , but evidence for effectiveness of EBM teaching on changing residents ’ behavior is limited . Objective To investigate the impact of an EBM curriculum on residents ’ use of evidence -based re sources in a simulated clinical experience . Design / Participants Fifty medicine residents r and omized to an EBM teaching or control group . Measurements A vali date d test of EBM knowledge ( Fresno test ) was administered before and after intervention . Post intervention , residents twice completed a Web-based , multiple-choice instrument ( 15 items ) comprised of clinical vignettes , first without then with access to electronic re sources . Use of electronic re sources was tracked using ProxyPlus software . Within group pre – post differences and between group post-test differences were examined . Results There was more improvement in EBM knowledge ( 100-point scale ) for the intervention group compared to the control group ( mean score increase 22 vs. 12 , p = 0.012 ) . In the simulated clinical experience , the most commonly accessed re sources were Ovid ( 71 % of residents accessed ) and InfoPOEMs ( 62 % ) for the EBM group and Upto Date ( 67 % ) and MDConsult ( 58 % ) for the control group . Residents in the EBM group were more likely to use evidence -based re sources than the control group . Performance on clinical vignettes was similar between the groups both at baseline ( p = 0.19 ) and with access to information re sources ( p = 0.89 ) . Conclusions EBM teaching improved EBM knowledge and increased use of evidence -based re sources by residents , but did not improve performance on Web-based clinical vignettes . Future studies will need to examine impact of EBM teaching on clinical outcomes Purpose To investigate whether teaching an evidence -based medicine ( EBM ) curriculum increased the knowledge and use of EBM principles in residents ' continuity clinics . Method In 1999 , the authors performed a needs assessment with residents and faculty of Cascades East Family Practice Residency in Oregon and constructed a ten-session EBM workshop series that was introduced into the curriculum in 2000 . Resident – preceptor interactions during outpatient continuity clinic were tape-recorded prior to and six months following introduction of the curriculum . A 50-item , multiple-choice examination was administered before and after the workshop series . Residents at another FP residency at the same university served as a control group . The same assessment s were applied to the experimental and control groups . The tape recordings were analyzed for interactions that contained key EBM phrases or words . Results Pre-intervention multiple-choice test results were similar ( control mean 56 % , experimental 53 % , p > .22 NS ) . Post-intervention test scores for the experimental group were significantly improved ( mean 72 % , p < .001 ) . There was no significant improvement in test results among members of the control group ( p > .05 NS ) . In the recorded resident – preceptor interactions , a marked increase in the use of EBM terms indicated awareness and /or use of EBM in the experimental group . In 1,165 minutes recorded prior to the workshops , EBM terms were used in a total of ten events . In 735 minutes recorded after the workshops , EBM terms were recorded in 67 events . A reduced number of EBM terms were recorded in the control group . Conclusion Administering a structured EBM curriculum increased residents ' knowledge and use of EBM constructs during patient care Music-based interventions are used to address a variety of problems experienced by individuals across the developmental lifespan ( infants to elderly adults ) . In order to improve the transparency and specificity of reporting music-based interventions , a set of specific reporting guidelines is recommended . Recommendations pertain to seven different components of music-based interventions , including theory , content , delivery schedule , interventionist , treatment fidelity , setting , and unit of delivery . Recommendations are intended to support Consoli date d St and ards for Reporting Trials ( CONSORT ) and Transparent Reporting of Evaluations with Non-r and omized Design s ( TREND ) statements for transparent reporting of interventions while taking into account the variety , complexity , and uniqueness of music-based interventions To adopt an evidence -based approach to education there is a need for research -based evidence to support its effectiveness . This study investigated the impact of evidence -based education on the knowledge and attitude of nursing students . In this quasi-experimental study , all nursing students ( n = 41 ) study ing the courses of musculoskeletal and gastrointestinal systems were chosen and assigned r and omly to intervention and control groups . The groups were taught through an evidence -based or traditional approach . Students ' knowledge and attitude were then evaluated . Data were gathered by three knowledge and two attitude question naires with multiple choice and Likert scales and then analyzed . It was shown that there was a significant difference between the average scores for attitude of the groups , but there was no statistically significant difference between the average scores of knowledge . The results suggest the evidence -based approach might be used as a complementary approach to nursing education . It was not only as effective as the usual method but also led to the acquisition of particular skills by students . The results can be used to formulate programs to design and implement evidence -based nursing education Background : Assessing in undergraduate medical education the educational effectiveness of a short computer-based session , integrating a lecturer 's video with a st and ardized structure , for evidence based medicine ( EBM ) teaching , compared to a lecture-based teaching session of similar structure and duration . Method : A concealed , r and omized controlled trial of computer based session versus lecture of equal duration ( 40 minutes ) and identical content in EBM and systematic review s. The study was based at the Medical School , University of Birmingham , UK involving one hundred and seventynine year one medical students . The main outcome measures were change from pre to post-intervention score measured using a vali date d question naire assessing knowledge ( primary outcome ) and attitudes ( secondary outcome ) . Results : Participants ’ improvement in knowledge in the computer based group was equivalent to the lecture based group ( gain in score : 0.8 [ S.D = 3.2 ] versus 1.3 [ S.D = 2.4 ] ; p = 0.24 ) . Attitudinal gains were similar in both groups . Conclusion : Computer based teaching and typical lecture sessions have similar educational gains We carried out a controlled trial of teaching the critical appraisal of clinical literature among final-year clinical clerks . Tutors at two of four teaching hospitals were offered a short course in the critical appraisal of clinical articles that describe diagnostic tests and treatments and were assisted in identifying and appraising specialty-specific articles that described those diagnostic tests and treatments that clinical clerks were sure to encounter during their clerkship tutorials . Tutors and clerks at the other two hospitals received no special intervention and served as controls . Experimental and control clinical clerks completed pretests and posttests of their ability to take and defend a st and on whether to apply specific diagnostic tests and treatments in specific clinical situations . Experimental clerks demonstrated both statistically and " clinical ly " significant increases in their critical appraisal skills , improving 37 % on the diagnostic test exercise and 8 % on the treatment exercise ; control students ' scores deteriorated for both 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 |
12,166 | 29,729,003 | This contributes to an appropriately tailored exercise regimen for every CVD risk patient | Whereas exercise training is key in the management of patients with cardiovascular disease ( CVD ) risk ( obesity , diabetes , dyslipidaemia , hypertension ) , clinicians experience difficulties in how to optimally prescribe exercise in patients with different CVD risk factors .
Therefore , a consensus statement for state-of-the-art exercise prescription in patients with combinations of CVD risk factors as integrated into a digital training and decision support system ( the EXercise Prescription in Everyday practice & Rehabilitative Training ( EXPERT ) tool ) needed to be established .
In this paper , state-of-the-art exercise prescription to patients with combinations of CVD risk factors is formulated , and it is shown how the EXPERT tool may assist clinicians . | Overweight and obesity affects more than 66 % of the adult population and is associated with a variety of chronic diseases . Weight reduction reduces health risks associated with chronic diseases and is therefore encouraged by major health agencies . Guidelines of the National Heart , Lung , and Blood Institute ( NHLBI ) encourage a 10 % reduction in weight , although considerable literature indicates reduction in health risk with 3 % to 5 % reduction in weight . Physical activity ( PA ) is recommended as a component of weight management for prevention of weight gain , for weight loss , and for prevention of weight regain after weight loss . In 2001 , the American College of Sports Medicine ( ACSM ) published a Position St and that recommended a minimum of 150 min wk(-1 ) of moderate-intensity PA for overweight and obese adults to improve health ; however , 200 - 300 min wk(-1 ) was recommended for long-term weight loss . More recent evidence has supported this recommendation and has indicated more PA may be necessary to prevent weight regain after weight loss . To this end , we have reexamined the evidence from 1999 to determine whether there is a level at which PA is effective for prevention of weight gain , for weight loss , and prevention of weight regain . Evidence supports moderate-intensity PA between 150 and 250 min wk(-1 ) to be effective to prevent weight gain . Moderate-intensity PA between 150 and 250 min wk(-1 ) will provide only modest weight loss . Greater amounts of PA ( > 250 min wk(-1 ) ) have been associated with clinical ly significant weight loss . Moderate-intensity PA between 150 and 250 min wk(-1 ) will improve weight loss in studies that use moderate diet restriction but not severe diet restriction . Cross-sectional and prospect i ve studies indicate that after weight loss , weight maintenance is improved with PA > 250 min wk(-1 ) . However , no evidence from well- design ed r and omized controlled trials exists to judge the effectiveness of PA for prevention of weight regain after weight loss . Resistance training does not enhance weight loss but may increase fat-free mass and increase loss of fat mass and is associated with reductions in health risk . Existing evidence indicates that endurance PA or resistance training without weight loss improves health risk . There is inadequate evidence to determine whether PA prevents or attenuates detrimental changes in chronic disease risk during weight gain OBJECTIVE To compare the response of blood glucose levels to intermittent high-intensity exercise ( IHE ) and moderate-intensity exercise ( MOD ) in individuals with type 1 diabetes . RESEARCH DESIGN AND METHODS Seven healthy individuals with type 1 diabetes were tested on two separate occasions , during which either a 30-min MOD or IHE protocol was performed . MOD consisted of continuous exercise at 40 % Vo(2peak ) , while the IHE protocol involved a combination of continuous exercise at 40 % Vo(2peak ) interspersed with 4-s sprints performed every 2 min to simulate the activity patterns of team sports . RESULTS Both exercise protocol s result ed in a decline in blood glucose levels . However , the decline was greater with MOD ( -4.4 + /- 1.2 mmol/l ) compared with IHE ( -2.9 + /- 0.8 mmol/l ; P < 0.05 ) , despite the performance of a greater amount of total work with IHE ( P < 0.05 ) . During 60 min of recovery from exercise , glucose levels remained higher in IHE compared with MOD ( P < 0.05 ) . Furthermore , glucose levels remained stable during recovery from IHE , while they continued to decrease after MOD ( P < 0.05 ) . The stabilization of blood glucose levels with IHE was associated with elevated levels of lactate , catecholamines , and growth hormone during early recovery from exercise ( P < 0.05 ) . There were no differences in free insulin , glucagon , cortisol , or free fatty acids between MOD and IHE . CONCLUSIONS The decline in blood glucose levels is less with IHE compared with MOD during both exercise and recovery in individuals with type 1 diabetes Exercise is an effective intervention for treating hypertension and arterial stiffness , but little is known about which exercise modality is the most effective in reducing arterial stiffness and blood pressure in hypertensive subjects . Our purpose was to evaluate the effect of continuous vs. interval exercise training on arterial stiffness and blood pressure in hypertensive patients . Sixty-five patients with hypertension were r and omized to 16 weeks of continuous exercise training ( n=26 ) , interval training ( n=26 ) or a sedentary routine ( n=13 ) . The training was conducted in two 40-min sessions a week . Assessment of arterial stiffness by carotid – femoral pulse wave velocity ( PWV ) measurement and 24-h ambulatory blood pressure monitoring ( ABPM ) were performed before and after the 16 weeks of training . At the end of the study , ABPM blood pressure had declined significantly only in the subjects with higher basal values and was independent of training modality . PWV had declined significantly only after interval training from 9.44±0.91 to 8.90±0.96 m s−1 , P=0.009 ( continuous from 10.15±1.66 to 9.98±1.81 m s−1 , P = ns ; control from 10.23±1.82 to 10.53±1.97 m s−1 , P = ns ) . Continuous and interval exercise training were beneficial for blood pressure control , but only interval training reduced arterial stiffness in treated hypertensive subjects Aims : Exercise is recommended as prevention , management , and control of all stages of hypertension . There are still controversies about the optimal training dose , frequency , and intensity . We aim ed to study the effect of aerobic interval training on blood pressure and myocardial function in hypertensive patients . Methods and results : A total of 88 patients ( 52.0 ± 7.8 years , 39 women ) with essential hypertension were r and omized to aerobic interval training ( AIT ) ( > 90 % of maximal heart rate , correlates to 85–90 % of VO2max ) , isocaloric moderate intensity continuous training ( MIT ) ( ∼70 % of maximal heart rate , 60 % of VO2max ) , or a control group . Exercise was performed on a treadmill , three times per week for 12 weeks . Ambulatory 24-hour blood pressure ( ABP ) was the primary endpoint . Secondary endpoints included maximal oxygen uptake ( VO2max ) , mean heart rate/24 hour , flow mediated dilatation ( FMD ) , total peripheral resistance ( TPR ) , and myocardial systolic and diastolic function by echocardiography . Systolic ABP was reduced by 12 mmHg ( p < 0.001 ) in AIT and 4.5 mmHg ( p = 0.05 ) in MIT . Diastolic ABP was reduced by 8 mmHg ( p < 0.001 ) in AIT and 3.5 mmHg ( p = 0.02 ) in MIT . VO2max improved by 15 % ( p < 0.001 ) in AIT and 5 % ( p < 0.01 ) in MIT . Systolic myocardial function improved in both exercise groups , diastolic function in the AIT group only . TPR reduction and increased FMD were only observed in the AIT group . Conclusions : This study indicates that the blood pressure reducing effect of exercise in essential hypertension is intensity dependent . Aerobic interval training is an effective method to lower blood pressure and improve other cardiovascular risk factors Background Although disease-specific exercise guidelines for cardiovascular disease ( CVD ) are widely available , it remains uncertain whether these different exercise guidelines are integrated properly for patients with different CVDs . The aim of this study was to assess the inter-clinician variance in exercise prescription for patients with various CVDs and to compare these prescriptions with recommendations from the EXercise Prescription in Everyday practice and Rehabilitative Training ( EXPERT ) tool , a digital decision support system for integrated state-of-the-art exercise prescription in CVD . Design The study was a prospect i ve observational survey . Methods Fifty-three CV rehabilitation clinicians from nine European countries were asked to prescribe exercise intensity ( based on percentage of peak heart rate ( HRpeak ) ) , frequency , session duration , programme duration and exercise type ( endurance or strength training ) for the same five patients . Exercise prescriptions were compared between clinicians , and relationships with clinician characteristics were studied . In addition , these exercise prescriptions were compared with recommendations from the EXPERT tool . Results A large inter-clinician variance was found for prescribed exercise intensity ( median ( interquartile range ( IQR ) ) : 83 ( 13 ) % of HRpeak ) , frequency ( median ( IQR ) : 4 ( 2 ) days/week ) , session duration ( median ( IQR ) : 45 ( 18 ) min/session ) , programme duration ( median ( IQR ) : 12 ( 18 ) weeks ) , total exercise volume ( median ( IQR ) : 1215 ( 1961 ) peak-effort training hours ) and prescription of strength training exercises ( prescribed in 78 % of all cases ) . Moreover , clinicians ’ exercise prescriptions were significantly different from those of the EXPERT tool ( p < 0.001 ) . Conclusions This study reveals significant inter-clinician variance in exercise prescription for patients with different CVDs and disagreement with an integrated state-of-the-art system for exercise prescription , justifying the need for st and ardization efforts regarding integrated exercise prescription in CV rehabilitation PURPOSE This study was design ed to investigate whether , in a dose-response manner , there would be greater health benefits in a group of postmenopausal women completing 45 minute- vs. 30 minutes of moderate intensity ( 50 % maximal oxygen uptake reserve , VO2R ) exercise 5 days . wk(-1 ) . METHODS Apparently healthy but sedentary postmenopausal women ( n = 33 ) were r and omized to a nonexercise control group , a 30-minute exercise duration group , or a 45-minute exercise duration group . Exercise training was performed 5 days . wk(-1 ) for 12 weeks at 50 % VO2R . Participants were instructed to not change their usual diet throughout the study . RESULTS Twenty-six women completed the study . After 12 weeks , VO2max increased significantly ( p < 0.05 ) in both 30-minute ( 0.20 + /- 0.21 L . min(-1 ) ) and 45-minute ( 0.41 + /- 0.10 L . min(-1 ) ) groups . Repeated measures ANOVA identified a significant interaction between exercise duration and VO2max values ( F = 4.72 , p < 0.05 ) , indicating that VO2max responded differently to 30-minute and 45-minute exercise duration s. Trend analysis showed that body mass , body composition , waist circumference , and high-density lipoprotein cholesterol ( HDL-C ) changed favorably ( p < 0.05 ) across control , 30-minute , and 45-minute groups . CONCLUSIONS Although most health organizations agree that 150 min . wk(-1 ) of physical activity will reduce the risk of all-cause and cardiovascular mortality , few r and omized , controlled studies have examined whether completing more physical activity than the recommended amount will yield additional benefits . Findings from the present study suggest that there is a dose-response relationship between exercise duration and numerous health outcomes in postmenopausal women , including cardiorespiratory fitness , body mass , body composition , waist circumference , and Summary No objective evidence has been presented to support the beneficial effect of physical training on glycaemic control in Type 1 ( insulin-dependent ) diabetic patients trained two to three times a week for several months . In the present study we examined the possibility that a daily exercise programme would be more suitable for improving glycaemic control . Thirteen patients completed a 5-month study ; 6 were r and omized to exercise training ( 20 min daily bicycle exercise ) and 7 served as non-exercising controls . The training result ed in an 8 % increase in maximal oxygen uptake ( p < 0.05 ) . No change in glycaemic control occurred during the study period in either group . In addition , serum lipid and lipoprotein levels were followed . Total cholesterol decreased during the study period irrespective of training . No effect was noted on the levels of LDL , VLDL , HDL and HDL2 cholesterol . A significant training effect was obtained in the HDL3 subfraction ( −10%,p < 0.05 ) . Total triglycerides were unchanged , but a decrease in the level of LDL triglycerides was observed with training ( −12%,p < 0.01 ) . It is concluded that , in female Type 1 diabetic patients , daily physical training for several months does not improve glycaemic control and results only in minor changes in serum lipoprotein profiles Background Impaired glucose tolerance ( IGT ) is associated with endothelial dysfunction and upregulation of inflammatory markers , which is potentially reversible by adequate treatment . It was our aim to compare the impact of exercise training with that of rosiglitazone on endothelial function and inflammatory markers in patients with IGT and coronary artery disease ( CAD ) . Methods Patients with IGT and CAD were r and omly assigned to either exercise training ( n = 13 ) , rosiglitazone ( 8 mg ; n = 11 ) , or a control group ( n = 10 ) . During the first week , exercise training consisted of 6 × 15 min/d followed by three weeks of 30 min/d submaximal ergometer exercise . In addition , group exercise training of 1 h was performed twice per week . Results After 4 weeks , triglycerides and uric acid were significantly lower in the exercise group whereas fasting glucose , HbA1c , low-density lipoprotein-cholesterol , high-density lipoprotein-cholesterol , C-reactive protein , fibrinogen , and body mass index did not differ between groups . In the exercise group , exercise capacity ( 123 ± 33 vs. 144 ± 31 W ; P = 0.006 ) and endothelium-dependent , flow-mediated vasodilatation ( P < 0.01 ) increased significantly , whereas in the rosiglitazone group and in the control group ( P = n.s . ) no changes were seen . Conclusion In patients with IGT and CAD , 4 weeks of exercise training exert significant and superior improvement of endothelium-dependent vasodilatation as compared with rosiglitazone therapy or usual care . This finding should be seen as an even further encouragement to recommend and , where available , prescribe exercise training to our patients . Eur J Cardiovasc Prev Rehabil 15:473 - 478 © 2008 The European Society of The goal of this study was to evaluate a program of resistance weight training on cardiovascular risk factors , blood glucose management , and overallstrength in diabetic subjects . A r and omized crossover design was performed on eight male type I ( insulin-dependent ) diabetic subjects ( mean ± SD age 31 ± 3.5 yr , height 176 ± 5.6 cm , body wt 80 ± 15 kg , duration of diabetes 12.3 ± 9.8 yr , and insulin dose 24 U NPH/day and 21 U regular/day ) . The program consisted of heavy-resistance weight training 3 days/wk for 10 wk , concentrating on the strengthening of major muscle groups through progressive resistance . Blood tests included total cholesterol , triglycerides , very-low-density lipoprotein and high-densitylipoprotein cholesterol , and HbA1c . These tests were repeated atthree time points during the program . Field-strength testing was performed before and after training . An improvement was seen in the squat ( 93.6 % increase , P < 0.0001 ) and bench press ( 58 % increase , P < 0.005 ) . HbA1c and triglyceride levels showed no change during the resting portion ofthe experiment but showed a significant change with the training program : HbA1c 6.9 ± 1 . 4 vs. 5.8 ± 0.9 % ( P = 0.05 ) and triglyceride 5.044 ± 1.06 vs. 4.628 ± 0.88 mM ( P = 0.01 ) . Self-monitored glucose ( taken pre- and postexercise ) showed a decrease from 7.85 ± 3.13 to 7.05 ± 2.91 mM ( P = 0.0001 ) . Very-low-density lipoprotein cholesterol and triglycerides did not change after training . Analysis of variance showed no significant differences over time from the three time points with regard to reductions in cardiovascular risk factors or HbA1c . Heavy-resistance strength training may be associated with a decrease inglycosylated hemoglobin and cholesterol in type I diabetic men after training , in addition to increasing overall strength OBJECTIVE To study the impact of physical activity on glycemic control and plasma lipids [ HDL cholesterol ( HDL-C ) , HDL-C subfractions , triglycerides , lipoprotein(a ) ] , blood pressure , weight , and abdominal fat and to determine the necessary short-term adaptations in diabetes management during intensive endurance training in patients with IDDM . RESEARCH DESIGN AND METHODS Well-controlled subjects with IDDM ( n = 20 ; HbA1c = 7.6 % ) engaged in a regular exercise program over a period of 3 months involving endurance sports such as biking , long-distance running , or hiking . Subjects were instructed to exercise at least 135 min per week . If baseline activity exceeded this level , subjects were to increase further their physical activity as much as possible and record the type and time of such activity . RESULTS During the 3-month intervention , physical activity increased from 195 ± 176 to 356 ± 164 min ( mean ± SD ) per week ( P < 0.001 ) . Physical fitness as assessed by VO2max increased from 2,914 ± 924 to 3,092 ± 905 ml/min ( P < 0.001 ) , and insulin sensitivity increased significantly ( steady-state plasma glucose [ SSPG ] decreased from 10.5 ± 4.8 to 7.0 ± 3.3 mmol/l ; P < 0.01 ) . Subsequently , LDL cholesterol decreased by 14 % ( P < 0.05 ) , and HDL and HDL3-C subfraction increased by 10 ( P < 0.05 ) and 16 % ( P < 0.05 ) , respectively . Systolic and diastolic blood pressure decreased significantly from 127 ± 9 to 124 ± 8 ( P < 0.05 ) and from 80 ± 5 to 77 ± 5 mmHg ( P < 0.01 ) , respectively . Resting heart rate decreased from 63 ± 6 to 59 ± 7 bpm ( P < 0.01 ) . Waist-to-hip circumference ratio decreased from 0.882 ± 0.055 to 0.858 ± 0.053 ( P < 0.001 ) , body weight decreased from 70.7 ± 10.4 to 68.7 ± 10.2 kg ( P = 0.003 ) , with a consequent decrease in body fat from 21.9 ± 8.2 to 18.0 ± 6.3 % ( P < 0.001 ) and an increase in lean body mass from 54.9 ± 12.2 to 56.8 ± 11.0 kg . These effects occurred independently of glycemic control . The overall frequency of severe hypoglycemic episodes was reduced from 0.14 to 0.10 per patient-year during the study period . CONCLUSIONS This study shows that increasing physical activity is safe and does not result in more hypoglycemic episodes and that there is a linear dose-response between increased physical activity and loss of abdominal fat and a decrease in blood pressure and lipid-related cardiovascular risk factors , with a preferential increase in the HDL3-C subfraction Summary Aim Our Working Group on Out-Patient Cardiac Rehabilitation ( AGAKAR ) has previously published guidelines , which were endorsed by the Austrian Society of Cardiology . It was the aim of this study to assess the short-term ( phase II ) and long-term ( phase III ) effects of these guidelines by use of a nationwide registry . Methods All Austrian out-patient rehabilitation facilities entered data into a data base of all consecutive patients who completed phase II ( 4–6 weeks ) and /or III ( 6–12 months ) rehabilitation between 1.1.2009–30.11.2011 . Results Data of 1432 phase II and 1390 phase III patients were assessed . Despite the wide spectrum of cardiac diseases patients ’ exercise capacity improved during phase II by 20 ( − 193 to 240 ) watts ; 91.0 % reached a systolic blood pressure < 140 mmHg ; 68.1 % an LDL < 100 mg/dl ; 69.8 % triglycerides < 150 mg/dl , and 66.2 % of male patients had a waist circumference < 102 cm . During phase III improvement in cardiovascular risk factors , quality of life , anxiety , and depression were further improved in an increasing number of patients . Conclusions Our data demonstrate beneficial short- and long-term effects of the Austrian model of out-patient cardiac rehabilitation and provide support for comprehensive long-term rehabilitation programs . Furthermore , our model might be helpful for those who are at the verge of initiating or modifying their programs . It is also hoped that these data will motivate colleagues to refer their patients to out-patient cardiac rehabilitation facilities and that our results may stimulate insurance companies to grant further and comprehensive contracts to provide access for all suitable patients .ZusammenfassungZielEs war Ziel dieser Studie , die Wirksamkeit der ambulanten kardiologischen Rehabilitation Phase II und III nach dem Modell der Arbeitsgemeinschaft für ambulante kardiologische Rehabilitation ( AGAKAR ) , folgend den Guidelines der Österreichischen Kardiologischen Gesellschaft ( ÖKG ) , zu untersuchen . Method ikAlle Ambulatorien , die Vertragspartner der Österreichischen Sozialversicherungen sind , gaben die Date n aller Patienten , die zwischen 1.1.2009–30.11.2011 eine ambulante kardiologische Rehabilitation der Phase II und III abschlossen , prospektiv in eine Web-basierte Date nbank ein . ErgebnisseEs gelangten für die Phase II 1432 und für die Phase III 1390 Date nsätze zur Auswertung . Während der Phase II verbesserten sich die Patienten um 20 ( -193 - 240 ) Watt , erreichten 91,0 % einen systolischen Blutdruck von < 140 mmHg , 66,1 % ein LDL < 100 mg/dl , 69,8 % Triglyceride < 150 mg/dl und bei den Männern 66,2 % einen Bauchumfang < 102 cm . Am Ende der Phase III wurden die Zielwerte von einem noch größeren Teil der Patienten erreicht , wobei die Ergebnisse dann am besten waren , wenn der Phase III eine ambulante anstelle einer stationären Phase II vorausging . Auch nahmen Depression i m Laufe der Phase II und III ab und verbesserte sich die Lebensqualität . SchlussfolgerungenDiese Date n beweisen die Wirksamkeit und Nachhaltigkeit der ambulanten kardiologischen Rehabilitation der Phase II und III nach dem Modell der AGAKAR und folgend den Guidelines der ÖKG , wobei die Phase III nicht nur nach einer ambulanten , sondern auch nach einer stationären Phase II nachhaltige Wirkung zeigte . Diese Ergebnisse sollten dazu Anlass geben , diese Evidenz-basierte und Leitlinien-konforme ambulante Rehabilitation lückenlos , flächendeckend , berufsbegleitend und wohnortnah anzubieten und nicht mehr nur auf wenige Zentren zu beschränken Aims /hypothesisWe investigated whether a 10-s maximal sprint effort performed immediately prior to moderate-intensity exercise provides another means to counter the rapid fall in glycaemia associated with moderate-intensity exercise in individuals with type 1 diabetes . Material s and methods Seven complication-free type 1 diabetic males ( 21.6 ± 3.6 years ; mean±SD ) with HbA1c levels of 7.4 ± 0.7 % injected their normal morning insulin dose and ate their usual breakfast . When post-meal glycaemia fell to ∼11 mmol/l , participants were asked to perform a 10-s all-out sprint ( sprint trial ) or to rest ( control trial ) immediately before cycling at 40 % of peak rate of oxygen consumption for 20 min , with both trials conducted in a r and om counterbalanced order . Results Sprinting did not affect the rapid fall in glycaemia during the subsequent bout of moderate-intensity exercise ( 2.9 ± 0.4 mmol/l in 20 min ; p = 0.00 ; mean±SE ) . However , during the following 45 min of recovery , glycaemia in the control trial decreased by 1.23 ± 0.60 mmol/l ( p = 0.04 ) while remaining stable in the sprint trial , subsequently decreasing in this latter trial at a rate similar to that in the control trial . The large increase in noradrenaline ( norepinephrine ) ( p = 0.005 ) and lactate levels ( p = 0.0005 ) may have contributed to the early post-exercise stabilisation of glycaemia in the sprint trial . During recovery , adrenaline ( epinephrine ) and NEFA levels increased marginally in the sprint trial , but other counter-regulatory hormones did not change significantly ( p < 0.05 ) . Conclusions /interpretationA 10-s sprint performed immediately prior to moderate-intensity exercise prevents glycaemia from falling during early recovery from moderate-intensity exercise in individuals with type 1 diabetes The Scottish Intercollegiate Guidelines Network ( SIGN ) develops evidence based clinical guidelines for the NHS in Scotl and . The key elements of the methodology are ( a ) that guidelines are developed by multidisciplinary groups ; ( b ) they are based on a systematic review of the scientific evidence ; and ( c ) recommendations are explicitly linked to the supporting evidence and grade d according to the strength of that evidence . Until recently , the system for grading guideline recommendations was based on the work of the US Agency for Healthcare Research and Quality ( formerly the Agency for Health Care Policy and Research ) . 1 2 However , experience over more than five years of guideline development led to a growing awareness of this system 's weaknesses . Firstly , the grading system was design ed largely for application to questions of effectiveness , where r and omised controlled trials are accepted as the most robust study design with the least risk of bias in the results . However , in many areas of medical practice r and omised trials may not be practical or ethical to undertake ; and for many questions other types of study design may provide the best evidence . Secondly , guideline development groups often fail to take adequate account of the method ological quality of individual studies and the overall picture presented by a body of evidence rather than individual studies or they fail to apply sufficient judgment to the overall strength of the evidence base and its applicability to the target population of the guideline . Thirdly , guideline users are often not clear about the implication s of the grading system . They misinterpret the grade of recommendation as relating to its importance , rather than to the strength of the supporting evidence , and may therefore fail to give due weight to low grade recommendations . # # # # Summary points A revised system of determining levels of evidence and grade s The aim of this r and omized , single-blinded cross-over study was to investigate the response of interleukin-6 ( IL-6 ) during moderate aerobic exercise in stable euglycaemia and hyperglycaemia in seven male patients with type 1 diabetes mellitus . IL-6 increased significantly over the entire study period in euglycaemia , but not in hyperglycaemia OBJECTIVE Exercise is a cornerstone of diabetes therapy in type 1 diabetes mellitus ( DMT1 ) patients . The type of exercise is important in determining the propensity to hypoglycemia . We assessed , by continuous glucose monitoring ( CGM ) , the glucose profiles during and in the following 20h after a session of two different types of exercise . RESEARCH DESIGN AND METHODS Eight male volunteers with well-controlled DMT1 were studied . They underwent 30min of both intermittent high-intensity exercise ( IHE ) and moderate-intensity exercise ( MOD ) in r and om order . Expired air was recorded during exercise , while metabolic and hormonal determinations were performed before and for 120 min after exercises . The CGM system and activity monitor were applied for the subsequent 20h . RESULTS Blood glucose level declined during both type of exercise . At 150 min following the start of exercise , plasma glucose content was slightly higher after IHE . No changes were observed in plasma insulin concentration . A significant increase of norepinephrine concentration was noticed during IHE . Between midnight and 6:00 a.m. the glucose levels were significantly lower after IHE than those observed after MOD ( area under the curve , 23.3 ± 3 vs. 16 ± 3 mg/dL/420 min [ P = 0.04 ] ; mean glycemia at 3 a.m. , 225 ± 31 vs. 147 ± 17 mg/dL [ P<0.05 ] ) . The number of hypoglycemic episodes after IHE was higher than that observed after MOD ( seven vs. two [ P<0.05 ] ) . CONCLUSIONS We demonstrate that ( 1 ) CGM is a useful approach in DMT1 patients who undergo an exercise program and ( 2 ) IHE is associated with delayed nocturnal hypoglycemia Objective It is not well known which exercise intensity is needed to obtain blood pressure reductions in response to endurance training . We therefore compared the effect of training at lower and higher intensity on blood pressure , and , in addition on other cardiovascular risk factors , in at least 55-year-old sedentary men and women . Methods We used a r and omized crossover design comprising three 10-week periods . In the first and third periods , participants exercised at , respectively , lower and higher intensity ( 33 and 66 % of heart rate reserve ) in r and om order , with a sedentary period in between . Training programmes were identical except for intensity and were performed three times , 1 h per week . Thirty-nine ( 18 men ) out of 48 r and omized participants completed the study ; age averaged 59 years . Results The change of aerobic power from baseline to the end of each period was more pronounced ( P < 0.05 ) with higher intensity ( + 3.70 ml/kg min ; P < 0.001 ) than with lower intensity training ( + 2.31 ml/kg min ; P < 0.001 ) . Systolic blood pressures at rest and during submaximal exercise were reduced with both intensities ( P < 0.01 ) , whereas diastolic office blood pressure was significantly reduced after higher intensity only ( P < 0.01 ) . There were no significant differences in blood pressure reduction between intensities . Ambulatory blood pressure remained unchanged after training . Only higher intensity training reduced weight ( −1.09 kg ; P < 0.001 ) , body fat ( −0.85 % ; P < 0.001 ) , plasma triglycerides ( −0.17 mmol/l ; P < 0.05 ) and oxidized low-density lipoprotein ( −5.92 U/l ; P < 0.01 ) . Conclusion Higher and lower intensity training reduces systolic office and exercise blood pressure to a similar extent , but does not alter ambulatory blood pressure ; only higher intensity training favourably affects anthropometric characteristics and blood lipids |
12,167 | 27,569,830 | The contribution of parental involvement on intervention effectiveness remains unclear . | INTRODUCTION Interventions targeting children 's dietary behavior often include strategies that target parents as implementation agents of change , though parent involvement on intervention effectiveness is unclear .
The present study systematic ally assessed ( 1 ) reporting of reach , effectiveness , adoption , implementation and maintenance ( RE- AIM ) of child dietary intervention studies with parents as change agents and ( 2 ) evaluated within these studies the comparative effectiveness of interventions with and without a parent component . | OBJECTIVE The objective was to compare targeting increased eating of healthy foods vs. reducing intake of high energy-dense foods within the context of a family-based behavioral weight control program . METHODS AND PROCEDURES Forty-one 8 - 12 year-old children > 85th BMI percentile were r and omly assigned to a 24-month family-based behavioral treatment that targeted increasing fruits and vegetables and low-fat dairy vs. reducing intake of high energy-dense foods . RESULTS Children in the increase healthy food group showed greater reduction in z BMI compared to children in the reduce high energy-dense food group at 12- ( -0.30 z BMI units vs. -0.15 z BMI units , P = 0.01 ) and 24- ( -0.36 z BMI units vs -0.13 z BMI units , P = 0.04 ) month follow-up . Parents in the increase healthy food group showed greater reductions in concern about child weight ( P = 0.007 ) , and these changes were associated with child z BMI change ( P = 0.008 ) . Children in the reduce high energy-dense group showed larger sustained reductions in high energy-dense foods ( P < 0.05 ) . Baseline levels of high energy-dense foods ( P < 0.05 ) , parent food restraint ( P = 0.01 ) , parent concern over parent weight ( P = 0.01 ) and parent acceptance of the child ( P < 0.05 ) moderated child z BMI change , with greater sustained reductions in z BMI for children in the increase healthy food group for each measure . Parent z BMI change followed the same pattern as child changes , and parent and child z BMI changes were correlated ( P < 0.001 ) . DISCUSSION Focusing on healthy food choices within an energy restricted diet may be useful in family-based weight control programs OBJECTIVE The study presents the immediate post-intervention results of Kids and Adults Now - Defeat Obesity ! , a r and omized controlled trial to enhance healthy lifestyle behaviors in mother-preschooler ( 2 - 5 years old ) dyads in North Carolina ( 2007 - 2011 ) . The outcomes include change from baseline in the child 's diet , physical activity and weight , and in the mother 's parenting behaviors , diet , physical activity , and weight . METHOD The intervention targeted parenting through maternal emotion regulation , home environment , feeding practice s , and modeling of healthy behaviors . 400 mother-child dyads were r and omized . RESULTS Mothers in the intervention arm , compared to the control arm , reduced instrumental feeding ( -0.24 vs. 0.01 , p<0.001 ) and TV snacks ( -.069 vs. -0.24 , p=0.001 ) . There were also improvements in emotional feeding ( p=0.03 ) , mother 's sugary beverage ( p=0.03 ) and fruit/vegetable ( p=0.04 ) intake , and dinners eaten in front of TV ( p=0.01 ) ; these differences were not significant after adjustment for multiple comparisons . CONCLUSION KAN-DO , design ed to maximize the capacity of mothers as agents of change , improved several channels of maternal influence . There were no group differences in the primary outcomes , but differences were observed in the parenting and maternal outcomes and there were trends toward improvement in the preschoolers ' diets . Long-term follow-up will address whether these short-term trends ultimately improve weight status PURPOSE To examine the feasibility and efficacy of a theory-driven and family-based program delivered online to promote healthy lifestyles and weights in Chinese American adolescents . METHODS A r and omized controlled study of a web-based intervention was developed and conducted in 54 Chinese American adolescents ( ages , 12 - 15 years ) and their families . Data on anthropometry , blood pressure , dietary intake , physical activity , and knowledge and self-efficacy regarding physical activity and nutrition were collected at baseline and 2 , 6 , and 8 months after the baseline assessment . Data were analyzed using linear mixed modeling . RESULTS The intervention result ed in significant decreases in waist-to-hip ratio and diastolic blood pressure and increases in vegetable and fruit intake , level of physical activity , and knowledge about physical activity and nutrition . CONCLUSION This web-based behavior program for Chinese American adolescents and their families seems feasible and effective in the short-term . Long-term effects remain to be determined . This type of program can be adapted for other minority ethnic groups who are at high-risk for overweight and obesity and have limited access to programs that promote healthy lifestyles This Scientific Statement addresses Parents and Adult Caregivers ( PACs ) as ‘ agents of change ’ for obese children . Evidence is review ed to support the notion that PACs can leverage behavior change and reduce positive energy balance in obese youth , and research opportunities for the field are discussed . The Statement has three specific aims : First , the core behavior change strategies for PACs as used in family-based treatment programs are review ed . These strategies reduce childhood overweight compared to no treatment or nutrition education alone , although their limited potency is recognized . Second , the strength of evidence is evaluated for the hypothesis that greater parental ‘ involvement ’ in treatment is associated with greater reductions in child overweight . Drawing upon r and omized clinical trials that varied the degree/nature of parental involvement , and observational analyses that assessed parental adherence to behavioral strategies , we report limited and inconsistent support . For example , only 17 % of the intervention studies reported differential improvements in child overweight as function of parental involvement after treatment . On the other h and , greater parental adherence predicted better child weight outcomes after 2 and 5 years in certain studies . Third , research gaps identified throughout this review process are delineated and new opportunities for the field are proposed . For example , the assessment of refined parenting phenotypes , cultural tailoring of interventions , examination of family relationships , and incorporating new technologies in treatment represent topics needing further study . A conceptual model is proposed to guide research on underst and ing the determinants of parental feeding and physical-activity parenting practice s. The Statement strives to innovate the scope and potency of PAC treatments for childhood obesity BACKGROUND Childhood obesity is a major public health problem in the United States , particularly among American Indian communities . OBJECTIVE The objective was to evaluate the effectiveness of a school-based , multicomponent intervention for reducing percentage body fat in American Indian schoolchildren . DESIGN This study was a r and omized , controlled , school-based trial involving 1704 children in 41 schools and was conducted over 3 consecutive years , from 3rd to 5th grade s , in schools serving American Indian communities in Arizona , New Mexico , and South Dakota . The intervention had 4 components : 1 ) change in dietary intake , 2 ) increase in physical activity , 3 ) a classroom curriculum focused on healthy eating and lifestyle , and 4 ) a family-involvement program . The main outcome was percentage body fat ; other outcomes included dietary intake , physical activity , and knowledge , attitudes , and behaviors . RESULTS The intervention result ed in no significant reduction in percentage body fat . However , a significant reduction in the percentage of energy from fat was observed in the intervention schools . Total energy intake ( by 24-h dietary recall ) was significantly reduced in the intervention schools but energy intake ( by direct observation ) was not . Motion sensor data showed similar activity levels in both the intervention and control schools . Several components of knowledge , attitudes , and behaviors were also positively and significantly changed by the intervention . CONCLUSIONS These results document the feasibility of implementing a multicomponent program for obesity prevention in elementary schools serving American Indian communities . The program produced significant positive changes in fat intake and in food- and health-related knowledge and behaviors . More intense or longer interventions may be needed to significantly reduce adiposity in this population This study tested the impact of a multicomponent intervention entitled " Partners of all Ages Reading About Diet and Exercise " ( PARADE ) a child-focused energy balance intervention incorporated into mentoring programs . We used a group r and omized nested cohort design r and omizing mentoring program sites ( n = 119 ) and children ( N = 782 ; females = 49 % ; African American = 37 % ; mean ( s.d . ) age = 8.5 ( 1.5 ) years ) to intervention or usual care conditions . PARADE mentors delivered eight lesson plans addressing key concepts related to diet and activity ; eight child-focused computer-tailored storybooks with messages targeting that child 's diet and activity patterns and eight parent action support newsletters . When compared to the control group , PARADE children were more knowledgeable of diet and activity guidelines ( P < 0.01 ) , challenged themselves more to eat five fruits and vegetables ( FV ) ( P < 0.01 ) and be active 1 h daily ( P < 0.01 ) , and to ask for FV for snack ( P = 0.015 ) . Calories from high fat foods decreased in overweight/obese children , but not for normal weight children ( P = 0.059 ) . There were no significant differences in fruit and vegetable intake , total calories , percent time being active , or BMI z-score . The combination of one-to-one mentoring , child-focused computer based tailoring , and parent support may impact important behavioral change precursors in environments over which the child has control , especially among normal weight children . Further , work is needed to evaluate the impact of family-focused multicomponent interventions , including computer-tailored approaches , directed toward both the parent and the child Background The family food environment is an important influence in the development of children ’s dietary habits . Research suggests that influences of current dietary behaviour and behaviour change may differ . The aims of this paper were to : ( 1 ) investigate the association between the food environment at baseline and change in children ’s saturated fat intake ; and ( 2 ) to explore whether a change in the food environment was associated with a change in children ’s saturated fat intake . MethodS econdary analysis of a 12 week cluster r and omised controlled trial in 133 4 - 13 year old children . Families were r and omly allocated to parental education regarding changing to reduced-fat dairy foods or a comparison non-dietary behaviour . The interventions were family focused . Parents received education from a dietitian in 3x30minute sessions to facilitate behaviour change . Parents completed a comprehensive question naire capturing three domains of the food environment – Parent knowledge and attitudes ; shaping practice s ; and behaviours and role modelling . Children ’s dietary intake was assessed via multiple 24-hour recalls at baseline and week 12 . Changes in the family food environment and primary outcome ( saturated fat ) were calculated . Hierarchical linear regression models were performed to explore the association between baseline and change in food environment constructs and change in saturated fat intake . St and ardised Beta are presented ( p<0.05 ) . Results After adjustments for child and family demographics , higher levels of perceived food availability ( β=-0.2 ) at baseline was associated with greater reduction in saturated fat intake , where as higher perceived responsibility ( β=0.2 ) , restriction ( β=0.3 ) and pressure to eat ( β=0.3 ) were associated with lesser change in saturated fat . An increase in nutrition knowledge ( β=-0.2 ) , perceived responsibility ( β=-0.3 ) and restriction ( β=-0.3 ) from baseline to week 12 were associated with greater reduction in saturated fat intake . Conclusions The present study was one of the first to quantify changes in the family food environment , and identify a number of factors which were associated with a positive dietary change . Because interventions focus on behaviour change , the findings may provide specific targets for intervention strategies in the future . Trial registration Australia New Zeal and Clinical Trials Registry ACTRN12609000453280 OBJECTIVE The High 5 for Preschool Kids ( H5-KIDS ) program tested the effectiveness of a home based intervention to teach parents how to ensure a positive fruit-vegetable ( FV ) environment for their preschool child , and to examine whether changes in parent behavior were associated with improvements in child intake . METHODS A group r and omized nested cohort design was conducted ( 2001 to 2006 ) in rural , southeast Missouri with 1306 parents and their children participating in Parents As Teachers , a national parent education program . RESULTS When compared to control parents , H5-KIDS parents reported an increase in FV servings ( MN=0.20 , p=0.05 ) , knowledge and availability of FV within the home ( p=0.01 ) , and decreased their use of noncoercive feeding practice s ( p=0.02 ) . Among preschoolers , FV servings increased in normal weight ( MN=0.35 , p=0.02 ) but not overweight children ( MN=-0.10 , p=0.48 ) , relative to controls . The parent 's change in FV servings was a significant predictor of child 's change in FV in the H5-KIDS group ( p=0.001 ) . CONCLUSION H5-KIDS suggests the need for , and promise of , early home intervention for childhood obesity prevention . It demonstrates the importance of participatory approaches in developing externally valid interventions , with the potential for dissemination across national parent education programs as a means for improving the intake of parents and young children OBJECTIVE To test the hypothesis that family dietary coaching would improve nutritional intakes and weight control in free-living ( noninstitutionalized ) children and parents . DESIGN R and omized controlled trial . SETTING Fifty-four elementary schools in Paris , France . PARTICIPANTS One thous and thirteen children ( mean age , 7.7 years ) and 1013 parents ( mean age , 40.5 years ) . INTERVENTION Families were r and omly assigned to group A ( advised to reduce fat and to increase complex carbohydrate intake ) , group B ( advised to reduce both fat and sugar and to increase complex carbohydrate intake ) , or a control group ( given no advice ) . Groups A and B received monthly phone counseling and Internet-based monitoring for 8 months . OUTCOME MEASURES Changes in nutritional intake , body mass index ( calculated as weight in kilograms divided by height in meters squared ) , fat mass , physical activity , blood indicators , and quality of life . RESULTS Compared with controls , participants in the intervention groups achieved their nutritional targets for fat intake and to a smaller extent for sugar and complex carbohydrate intake , leading to a decrease in energy intake ( children , P < .001 ; parents , P = .02 ) . Mean changes in body mass index were similar among children ( group A , + 0.05 , 95 % confidence interval [ CI ] , - 0.06 to 0.16 ; group B , + 0.10 , 95 % CI , - 0.03 to 0.23 ; control group , + 0.13 , 95 % CI , 0.04 - 0.22 ; P = .45 ) , but differed in parents ( group A , + 0.13 , 95 % CI , - 0.01 to 0.27 ; group B , - 0.02 , 95 % CI , - 0.14 to 0.11 ; control group , + 0.24 , 95 % CI , 0.13 - 0.34 ; P = .001 ) , with a significant difference between group B and the control group ( P = .01 ) . CONCLUSIONS Family dietary coaching improves nutritional intake in free-living children and parents , with beneficial effects on weight control in parents . Trial Registration clinical trials.gov Identifier : NCT00456911 BACKGROUND This study evaluated the effects of a school-based dietary intervention program to increase fruit and vegetable consumption among fourth- grade rs . METHODS Twenty-eight elementary schools were r and omized to an immediate intervention condition or to a delayed intervention control condition . Measures of diet and psychosocial variables were collected at base line and 1 and 2 years post-baseline . The intervention included classroom , parent , and cafeteria components . RESULTS Mean daily consumption of fruit and vegetables was higher for the intervention children compared with controls at Follow-up 1 ( X(t ) = 3.96 , X(c ) = 2.28 ) and at Follow-up 2 ( X(t ) = 3.20 , X(c ) = 2.21 ) . Macro- and micronutrient changes favoring the intervention children were also observed at both Follow-up 1 and Follow-up 2 . Mean daily consumption of fruit and vegetables was higher for intervention parents compared with controls at Follow-up 1 ( X(t ) = 4.23,X(c ) = 3.94 ) but not at Follow-up 2 . CONCLUSIONS Strong effects were found for the High 5 intervention on fruit and vegetable consumption , on macro- and micro-nutrients , and on psychosocial variables . Future work is needed to enhance the intervention effects on parents ' consumption and to test the effectiveness of the intervention when delivered by classroom teachers Objective To investigate the effectiveness of a school based intervention to increase physical activity , reduce sedentary behaviour , and increase fruit and vegetable consumption in children . Design Cluster r and omised controlled trial . Setting 60 primary schools in the south west of Engl and . Participants Primary school children who were in school year 4 ( age 8 - 9 years ) at recruitment and baseline assessment , in year 5 during the intervention , and at the end of year 5 ( age 9 - 10 ) at follow-up assessment . Intervention The Active for Life Year 5 ( AFLY5 ) intervention consisted of teacher training , provision of lesson and child-parent interactive homework plans , all material s required for lessons and homework , and written material s for school newsletters and parents . The intervention was delivered when children were in school year 5 ( age 9 - 10 years ) . Schools allocated to control received st and ard teaching . Main outcome measures The pre-specified primary outcomes were accelerometer assessed minutes of moderate to vigorous physical activity per day , accelerometer assessed minutes of sedentary behaviour per day , and reported daily consumption of servings of fruit and vegetables . Results 60 schools with more than 2221 children were recruited ; valid data were available for fruit and vegetable consumption for 2121 children , for accelerometer assessed physical activity and sedentary behaviour for 1252 children , and for secondary outcomes for between 1825 and 2212 children for the main analyses . None of the three primary outcomes differed between children in schools allocated to the AFLY5 intervention and those allocated to the control group . The difference in means comparing the intervention group with the control group was –1.35 ( 95 % confidence interval –5.29 to 2.59 ) minutes per day for moderate to vigorous physical activity , –0.11 ( –9.71 to 9.49 ) minutes per day for sedentary behaviour , and 0.08 ( –0.12 to 0.28 ) servings per day for fruit and vegetable consumption . The intervention was effective for three out of nine of the secondary outcomes after multiple testing was taken into account : self reported time spent in screen viewing at the weekend ( –21 ( –37 to –4 ) minutes per day ) , self reported servings of snacks per day ( –0.22 ( –0.38 to –0.05 ) ) , and servings of high energy drinks per day ( –0.26 ( –0.43 to –0.10 ) ) were all reduced . Results from a series of sensitivity analyses testing different assumptions about missing data and from per protocol analyses produced similar results . Conclusion The findings suggest that the AFLY5 school based intervention is not effective at increasing levels of physical activity , decreasing sedentary behaviour , and increasing fruit and vegetable consumption in primary school children . Change in these activities may require more intensive behavioural interventions with children or upstream interventions at the family and societal level , as well as at the school environment level . These findings have relevance for research ers , policy makers , public health practitioners , and doctors who are involved in health promotion , policy making , and commissioning services . Trial registration Current Controlled Trials IS RCT N50133740 OBJECTIVE The goal of this study was to evaluate the effect of a parent-focused behavioral intervention on parent and child eating changes and on percentage of overweight changes in families that contain at least one obese parent and a non-obese child . RESEARCH METHODS AND PROCEDURES Families with obese parents and non-obese children were r and omized to groups in which parents were provided a comprehensive behavioral weight-control program and were encouraged to increase fruit and vegetable intake or decrease intake of high-fat/high-sugar foods . Child material s targeted the same dietary changes as their parents without caloric restriction . RESULTS Changes over 1 year showed that treatment influenced targeted parent and child fruit and vegetable intake and high-fat/high-sugar intake , with the Increase Fruit and Vegetable group also decreasing their consumption of high-fat/high-sugar foods . Parents in the increased fruit and vegetable group showed significantly greater decreases in percentage of overweight than parents in the decreased high-fat/high-sugar group . DISCUSSION These results suggest that focusing on increasing intake of healthy foods may be a useful approach for nutritional change in obese parents and their children Background The Active For Life Year 5 ( AFLY5 ) r and omised controlled trial protocol was published in this journal in 2011 . It provided a summary analysis plan . This publication is an up date of that protocol and provides a detailed analysis plan . Up date This up date provides a detailed analysis plan of the effectiveness and cost-effectiveness of the AFLY5 intervention . The plan includes details of how variables will be quality control checked and the criteria used to define derived variables . Details of four key analyses are provided : ( a ) effectiveness analysis 1 ( the effect of the AFLY5 intervention on primary and secondary outcomes at the end of the school year in which the intervention is delivered ) ; ( b ) mediation analyses ( secondary analyses examining the extent to which any effects of the intervention are mediated via self-efficacy , parental support and knowledge , through which the intervention is theoretically believed to act ) ; ( c ) effectiveness analysis 2 ( the effect of the AFLY5 intervention on primary and secondary outcomes 12 months after the end of the intervention ) and ( d ) cost effectiveness analysis ( the cost-effectiveness of the AFLY5 intervention ) . The details include how the intention to treat and per- protocol analyses were defined and planned sensitivity analyses for dealing with missing data . A set of dummy tables are provided in Additional file 1 . Discussion This detailed analysis plan was written prior to any analyst having access to any data and was approved by the AFLY5 Trial Steering Committee . Its publication will ensure that analyses are in accordance with an a priori plan related to the trial objectives and not driven by knowledge of the data .Trial registration IS RCT Background Low levels of physical activity , high levels of sedentary behaviour and low levels of fruit and vegetable consumption are common in children and are associated with adverse health outcomes . The aim of this paper is to describe the protocol for a cluster r and omised controlled trial ( RCT ) design ed to evaluate a school-based intervention that aims to increase levels of physical activity , decrease sedentary behaviour and increase consumption of fruit and vegetables in school children . Methods / design The Active for Life Year 5 ( AFLY5 ) study is a school-based , cluster RCT that targets school children in Year 5 ( age 9 - 10 years ) . All state junior/ primary schools in the area covered by Bristol City and North Somerset Council are invited to participate ; special schools are excluded . Eligible schools are r and omised to one of two arms : intervention arm ( receive the intervention 2011 - 2012 ) and control arm ( receive the intervention after the final follow-up assessment , 2013 - 2014 ) . The primary outcomes of the trial are levels of accelerometer assessed physical activity and sedentary behaviour and question naire assessed fruit and vegetable consumption . A number of secondary outcomes will also be measured , including body mass index , waist circumference and overweight/obesity . Outcomes will be assessed at baseline ( prior to intervention when the children are in Year 4 ) , at the end of intervention ' immediate follow-up ' and ' 12 months long-term ' follow-up . We will use r and om effects linear and logistic regression models to compare outcomes by r and omised arm . The economic evaluation from a societal perspective will take the form of a cost consequence analysis . Data from focus groups and interviews with pupils , parents and teachers will be used to increase underst and ing of how the intervention has any effect and is integrated into normal school activity . Discussion The results of the trial will provide information about the public health effectiveness of a school-based intervention aim ed at improving levels of physical activity , sedentary behaviour and diet in children . Trial registration IS RCT BACKGROUND Dairy foods are nutrient rich but also a source of saturated fat in the diets of children . OBJECTIVE We assessed effects on dietary intakes and health outcomes of changing dairy foods consumed by children from regular- to reduced-fat varieties . DESIGN This study was a 24-wk cluster r and omized controlled trial in 93 families with 4 - 13-y-olds who were r and omly allocated to parental education regarding changing to reduced-fat dairy foods ( n = 76 children ) or reducing screen time ( n = 69 children ) . Study outcomes , which were measured at weeks 0 , 12 ( end of the intervention ) , and 24 , included saturated fat , energy , and nutrient intakes ; pentadecanoic acid and blood lipid concentrations ; body mass index z score ; and waist circumference . Multilevel analyses were used with adjustment for child- and family-level covariates . RESULTS There were no group differences in overall dairy intakes ( -45 g dairy ; 95 % CI : -141 , 51 g dairy ; P = 0.356 ) . Saturated fat intakes were 3.3 percentage points lower ( P < 0.0001 ) in the intervention group at week 24 than in the comparison group . Pentadecanoic acid concentrations were lower at week 12 ( 0.03 % ; P = 0.012 ) but not at week 24 . LDL-cholesterol concentrations were not different at week 12 , but LDL-cholesterol concentration was 0.15 mmol/L lower in the intervention group at week 24 than in the comparison group ( P = 0.037 ) . There were no significant group differences in total energy or adiposity measures . Regular-fat dairy foods decreased from 88 % to 14 % of dairy intake in the intervention group . Calcium , magnesium , and carbohydrate ( percentage of energy ) intakes were higher in the intervention group than in the comparison group ; retinol intakes were lower in the intervention group than in the comparison group ; and overall vitamin A intakes were similar between groups . CONCLUSION Advice to parents to change to reduced-fat products was effective in reducing children 's saturated fat intakes but did not alter energy intakes or measures of adiposity . This trial was registered in the Australia New Zeal and Clinical Trials Registry as ACTRN12609000453280 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 OBJECTIVES A r and omized school based trial sought to increase fruit and vegetable consumption among children using a multicomponent approach . METHODS The intervention , conducted in 20 elementary schools in St. Paul , targeted a multiethnic group of children who were in the fourth grade in spring 1995 and the fifth grade in fall 1995 . The intervention consisted of behavioral curricula in classrooms , parental involvement , school food service changes , and industry support and involvement . Lunchroom observations and 24-hour food recalls measured food consumption . Parent telephone surveys and a health behavior question naire measured psychosocial factors . RESULTS The intervention increased lunchtime fruit consumption and combined fruit and vegetable consumption , lunchtime vegetable consumption among girls , and daily fruit consumption as well as the proportion of total daily calories attributable to fruits and vegetables . CONCLUSIONS Multicomponent school-based programs can increase fruit and vegetable consumption among children . Greater involvement of parents and more attention to increasing vegetable consumption , especially among boys , remain challenges in future intervention research OBJECTIVE To evaluate the impact of a school-based diabetes mellitus prevention program on low-income fourth- grade Mexican American children . DESIGN A r and omized controlled trial with 13 intervention and 14 control schools . SETTING Elementary schools in inner-city neighborhoods in San Antonio , Tex . PARTICIPANTS Eighty percent of participants were Mexican American and 94 % were from economically disadvantaged households . Baseline and follow-up measures were collected from 1419 ( 713 intervention and 706 control ) and 1221 ( 619 intervention and 602 control ) fourth- grade children , respectively . INTERVENTION The Bienestar Health Program consists of a health class and physical education curriculum , a family program , a school cafeteria program , and an after-school health club . The objectives are to decrease dietary saturated fat intake , increase dietary fiber intake , and increase physical activity . MAIN OUTCOME MEASURES The primary end point was fasting capillary glucose level , and the secondary end points were percentage of body fat , physical fitness level , dietary fiber intake , and dietary saturated fat intake . Fasting capillary glucose level , bioelectric impedance , modified Harvard step test , three 24-hour dietary recalls , weight , and height were collected at baseline and 8 months later . RESULTS Children in the intervention arm attended an average of 32 Bienestar sessions . Mean fasting capillary glucose levels decreased in intervention schools and increased in control schools after adjusting for covariates ( -2.24 mg/dL [ 0.12 mmol/L ] ; 95 % confidence interval , -6.53 to 2.05 [ -0.36 to 0.11 mmol/L ] ; P = .03 ) . Fitness scores ( P = .04 ) and dietary fiber intake ( P = .009 ) significantly increased in intervention children and decreased in control children . Percentage of body fat ( P = .56 ) and dietary saturated fat intake ( P = .52 ) did not differ significantly between intervention and control children . CONCLUSION This intervention showed some positive results , but additional research is needed to examine long-term benefits , translation , and cost-effectiveness Background Consumption of non-core foods in childhood is associated with excessive weight gain in childhood . Parents play a vital role in establishing healthy diet behaviours in young children . The aim of this study was to assess the effectiveness of a telephone-based intervention in reducing child consumption of non-core foods , and to examine parent and home food environment mediators of change in child consumption . Methods The ‘ Healthy Habits ’ trial utilised a clustered r and omised controlled design . Setting / participants Parents were recruited from 30 preschools ( N = 394 participants , mean age 35.2±5.6 years ) . Parents r and omized to the intervention group received four telephone contacts and print material s. Parents allocated to the control condition receive generic print material s only . Non-core food consumption was assessed using a vali date d child dietary question naire at baseline , 2 and 6 months post recruitment in 2010 . Results The intervention was effective in reducing child consumption of non-core foods at 2 months ( intention to treat analysis : z=-2.83 , p<.01 ) , however this effect was not maintained at 6 months . Structural equation modelling using 2 month data indicated that child access to non-core foods in the home and child feeding strategies mediated the effect of the intervention . Conclusion The telephone-based intervention shows promise in improving short term dietary behaviour in preschool age children , however further development is needed to sustain the effect in the long-term . Trial registration Australian Clinical Trials Registry : BACKGROUND . The prevalence and seriousness of childhood obesity has prompted calls for broad public health solutions that reach beyond clinic setting s. Schools are ideal setting s for population -based interventions to address obesity . OBJECTIVE . The purpose of this work was to examine the effects of a multicomponent , School Nutrition Policy Initiative on the prevention of overweight ( 85.0th to 94.9th percentile ) and obesity ( > 95.0th percentile ) among children in grade s 4 through 6 over a 2-year period . METHODS . Participants were 1349 students in grade s 4 through 6 from 10 schools in a US city in the Mid-Atlantic region with ≥50 % of students eligible for free or reduced-price meals . Schools were matched on school size and type of food service and r and omly assigned to intervention or control . Students were assessed at baseline and again after 2 years . The School Nutrition Policy Initiative included the following components : school self- assessment , nutrition education , nutrition policy , social marketing , and parent outreach . RESULTS . The incidences of overweight and obesity after 2 years were primary outcomes . The prevalence and remission of overweight and obesity , BMI z score , total energy and fat intake , fruit and vegetable consumption , body dissatisfaction , and hours of activity and inactivity were secondary outcomes . The intervention result ed in a 50 % reduction in the incidence of overweight . Significantly fewer children in the intervention schools ( 7.5 % ) than in the control schools ( 14.9 % ) became overweight after 2 years . The prevalence of overweight was lower in the intervention schools . No differences were observed in the incidence or prevalence of obesity or in the remission of overweight or obesity at 2 years . CONCLUSION . A multicomponent school-based intervention can be effective in preventing the development of overweight among children in grade s 4 through 6 in urban public schools with a high proportion of children eligible for free and reduced-priced school meals OBJECTIVE To evaluate the effects of a 2-year middle school physical activity and healthy food intervention , including an environmental and computer-tailored component on BMI and BMI z-score in boys and girls . RESEARCH METHODS AND PROCEDURES A r and om sample of 15 schools with seventh and eighth grade rs was r and omly assigned to three conditions : an intervention with parental support group , an intervention-alone group , and a control group . Weight and height were measured at the beginning and end of each school year to assess BMI and BMI z-score . A physical activity and healthy food program was implemented over 2 school years . RESULTS In girls , BMI and BMI z-score increased significantly less in the intervention with parental support group compared with the control group ( p < 0.05 ) or the intervention-alone group ( p = 0.05 ) . In boys , no significant positive intervention effects were found . DISCUSSION This was the first study evaluating the effectiveness of an intervention combining environmental changes with personal computer-tailored feedback on BMI and BMI z-score in middle school children . After 2 school years , BMI and BMI z-score changed in a more positive direction in girls as a result of the intervention with parental support OBJECTIVE To assess the short-term ( 15-d ) and long-term ( 12-month ) effects of a school-based health and nutrition education intervention on diet , nutrition intake and BMI . DESIGN The 12-week teacher-implemented intervention in combination with seminars organized for parents was aim ed at improving children 's diet and nutrition knowledge . The intervention took place between September 2007 and January 2008 . The participants were r and omized to two study groups , the intervention group ( IG ) and control group ( CG ) , and were examined prior to the intervention on a variety of health knowledge , dietary , behavioural and anthropometric indices . The same measurements were collected 15 d and 1 year after the intervention . SETTING All high schools in Vyronas , a densely populated district of Athens , Greece . SUBJECTS The sample consisted of 191 students aged 12 - 13 years . RESULTS Twelve months after the intervention , the programme was effective in reducing various indices in the IG compared with baseline findings ( BMI : 23.3 ( sd 2.8 ) v. 24.0 ( sd 3.1 ) kg/m2 , P < 0.001 ; daily energy intake : 8112.4 ( sd 1412.4 ) v. 8503.3 ( sd 1419.3 ) kJ/d , P < 0.001 ; total fat intake : 31.3 ( sd 4.4 ) v. 35.4 ( sd 4.7 ) % of daily energy , P < 0.001 ) . Except for BMI , decreases in the aforementioned indices were also observed 15 d after the intervention . In addition , students of the IG reduced their weekly consumption of red meat and non-home-made meals and increased their frequency of fruit and breakfast cereal consumption . CONCLUSIONS The beneficial effects of this nutrition education intervention among adolescents may highlight the potential of such programmes in the prevention of obesity A five-year intervention study of the effectiveness of the " Know Your Body " program in reducing coronary heart disease risk factors among black students in the District of Columbia , who were in grade s 4 - 6 at baseline , was begun in 1983 . Nine schools were stratified on socioeconomic status and r and omly assigned to control and intervention groups . The " Know Your Body " curriculum focuses on nutrition , fitness , and the prevention of cigarette smoking . At baseline , 1,234 students were eligible for the screening in which the following target risk factors were measured : systolic and diastolic blood pressures , ponderosity index , triceps skinfold thickness , postexercise pulse recovery rate , serum total and high density lipoprotein ( HDL ) cholesterol , and serum thiocyanate . After two years of intervention , results indicated that the program may have had a favorable impact on the following risk factors : systolic and diastolic pressures , HDL cholesterol , ratio of total to HDL cholesterol , fitness ( postexercise pulse recovery rate ) , and smoking . Significant net changes in the favorable direction also were found for health knowledge and attitude toward smoking . Blood pressure reduction was associated with decreased ponderosity and improved fitness , and increased HDL cholesterol was associated with decreased ponderosity . These results are consistent with other evaluations of the " Know Your Body " program , suggesting that the program may be effective in reducing chronic disease risk in diverse school population BACKGROUND Physical inactivity is a risk behavior for cardiovascular and other diseases . Schools can promote public health objectives by increasing physical activity among youth . METHODS The Child and Adolescent Trial for Cardiovascular Health ( CATCH ) was a multicenter , r and omized trial to test the effectiveness of a cardiovascular health promotion program in 96 public schools in four states . A major component of CATCH was an innovative , health-related physical education ( P+ ) program . For 2.5 years , r and omly assigned schools received a st and ardized PE intervention , including curriculum , staff development , and follow-up . RESULTS Systematic analysis of 2,096 PE lessons indicated students engaged in more moderate-to-vigorous physical activity ( MVPA ) in intervention than in control schools ( P = 0.002 ) . MVPA during lessons in intervention schools increased from 37.4 % at baseline to 51.9 % , thereby meeting the established Year 2000 objective of 50 % . Intervention children reported 12 more min of daily vigorous physical activity ( P = 0.003 ) and ran 18.6 yards more than control children on a 9-min run test of fitness ( P = 0.21 ) . CONCLUSIONS The implementation of a st and ardized curriculum and staff development program increased children 's MVPA in existing school PE classes in four geographic and ethnically diverse communities . CATCH PE provides a tested model for improving physical education in American schools OBJECTIVE Hip-Hop to Health Jr. was a diet/physical activity intervention design ed to reduce gains in BMI ( kilograms per meter squared ) in preschool minority children . RESEARCH METHODS AND PROCEDURES Twelve predominantly Latino Head Start centers participated in a group-r and omized trial conducted between Fall 2001 and Winter 2003 . Six centers were r and omized to a culturally proficient 14-week ( three times weekly ) diet/physical activity intervention . Parents participated by completing weekly homework assignments . The children in the other six centers received a general health intervention that did not address either diet or physical activity . The primary outcome was change in BMI , and secondary outcomes were changes in dietary intake and physical activity . Measures were collected at baseline , post-intervention , and at Years 1 and 2 follow-up . RESULTS There were no significant differences between intervention and control schools in either primary or secondary outcomes at post-intervention , Year 1 , or Year 2 follow-ups . DISCUSSION When Hip-Hop to Health Jr. was conducted in predominantly black Head Start centers , it was effective in reducing subsequent increases in BMI in preschool children . In contrast , when the program was conducted in Latino centers , it was not effective . Although the intervention did not prevent excessive weight gain in Latino children , it was very well received . Future interventions with this population may require further cultural tailoring and a more robust parent intervention OBJECTIVE This study evaluated whether a nutrition-education program in child-care centers improved children 's at-home daily consumption of fruits and vegetables , at-home use of low-fat/fat-free milk , and other at-home dietary behaviors . MATERIAL S AND METHODS Twenty-four child-care centers serving low-income families were matched by region , type , and size , and then r and omly assigned to either an intervention or control condition . In the 12 intervention centers , registered dietitian nutritionists provided nutrition education to children and parents separately during a 6- to 10-week period . They also held two training sessions for center staff , to educate them on healthy eating and physical activity policies at the centers , and distributed weekly parent newsletters that included activities and recipes . Parents ( n=1,143 ) completed a mail or telephone survey at baseline and follow-up to report information on their child 's fruit , vegetable , and milk consumption and other dietary behaviors at home . This study used general and generalized linear mixed models to evaluate program impacts , while accounting for the clustering of children within centers . This study included child age , child sex , household size , respondent race/ethnicity , respondent age , and respondent sex as covariates . RESULTS The program had a substantial impact on children 's at-home daily consumption of vegetables and use of low-fat/fat-free milk . This study also found a significant increase in the frequency of child-initiated vegetable snacking , which might have contributed to the significant increase in vegetable consumption . The program did not have a significant impact on fruit consumption or parental offerings of fruits and vegetables , child-initiated fruit snacking , or child fruit consumption . CONCLUSIONS This intervention in child-care setting s that emphasized children , parents , and teachers significantly increased at-home vegetable and low-fat/fat-free milk consumption among low-income preschoolers The effectiveness of a family-based cardiovascular disease risk reduction intervention was evaluated in two ethnic groups . Participants were 206 healthy , volunteer low-to-middle-income Mexican-American and non-Hispanic white ( Anglo-American ) families ( 623 individuals ) , each with a fifth or a sixth- grade child . Families were recruited through elementary schools . Half of the families were r and omized to a year-long educational intervention design ed to decrease the whole family 's intake of high salt , high fat foods , and to increase their regular physical activity . Eighty-nine percent of the enrolled families were measured at the 24-month follow-up . Both Mexican- and Anglo-American families in the experimental groups gained significantly more knowledge of the skills required to change dietary and exercise habits than did those in the control groups . Experimental families in both ethnic groups reported improved eating habits on a food frequency index . Anglo families reported lower total fat and sodium intake . There were no significant group differences in reported physical activity or in tested cardiovascular fitness levels . Significant differences for Anglo-American experimental vs. control adult subjects were found for LDL cholesterol . Significant intervention-control differences ranging from 2.2 to 3.4 mmHg systolic and /or diastolic blood pressure were found in all subgroups . Direct observation of diet and physical activity behaviors in a structured environment suggested generalization of behavior changes . There was evidence that behavior change persisted one year beyond the completion of the intervention program . It is concluded that involvement of families utilizing school based re sources is feasible and effective . Future studies should focus on the most cost-effective methods of family involvement , and the potential for additive effects when family strategies are combined with other school health education programs A theory-based multicomponent intervention ( Gimme 5 ) was design ed and implemented to impact fourth- and fifth- grade children ’s fruit , juice , and vegetable ( FJV ) consumption and related psychosocial variables . Gimme 5 was a r and omized controlled intervention trial with school ( n = 16 elementary ) as unit of r and om assignment and analysis . Participants included the cohort of students who were in the third grade in the winter of 1994 and students who joined them in the fourth and fifth grade s. The intervention included a curriculum , newsletters , videotapes , and point-of-purchase education . Evaluation included 7-day food records and psychosocial measures from students , telephone interviews with parents , and observational assessment s. Favorable results were observed for consumption of FJV combined , FJV consumed at weekday lunch , eating FJV self-efficacy , social norms , asking behaviors , and knowledge . A theory-based school nutrition education program can help change children ’s FJV consumption and impact factors at home that predispose to FJV consumption , but changes were small , and their persistence is unknown BACKGROUND Programs to improve cardiovascular health in schoolchildren need careful scientific evaluation . METHOD In a r and omized controlled trial of nutrition and fitness programs over a period of about 9 months , 1,147 10- to 12-year-olds from 30 schools were allocated to one of five health programs : fitness , fitness + school nutrition , school-based nutrition , school + home nutrition , home-based nutrition , or a control group . Nutrient intake , fitness , anthropometry , blood pressure , and blood cholesterol were measured before and after intervention . RESULTS Fitness increased and diastolic blood pressure and triceps skinfolds decreased significantly for girls in the fitness groups . Baseline consumption of sugar , fat , and fiber was outside national guidelines ; blood cholesterol exceeded recommendations in one-third of children . In girls , fat intake decreased significantly in the two home nutrition groups and fiber intake increased in the school + home nutrition and fitness groups . Boys in the fitness , fitness + school nutrition , and school + home nutrition group reduced sugar intake . Change in sugar intake correlated negatively with change in fat intake in both boys and girls . CONCLUSIONS Teacher-implemented health packages are feasible with minimal training but programs should differ between boys and girls . Fitness programs were more successful than nutrition education particularly in girls . Clearer nutrition messages should prevent reciprocal changes in sugar and fat . For girls , the 3 mm Hg reduction of diastolic blood pressure , less obesity , and increased fitness could translate into a substantial reduction in cardiovascular risk in adult life OBJECTIVE Many adolescents do not meet national guidelines for participation in regular moderate or vigorous physical activity ( PA ) ; limitations on sedentary behaviors ; or dietary intake of fruits and vegetables , fiber , or total dietary fat . This study evaluated a health care-based intervention to improve these behaviors . DESIGN R and omized controlled trial . SETTING Primary care with follow-up at home . PARTICIPANTS Eight hundred seventy-eight adolescent girls and boys aged 11 to 15 years . INTERVENTIONS Two experimental conditions : ( 1 ) Primary care , office-based , computer-assisted diet and PA assessment and stage-based goal setting followed by brief health care provider counseling and 12 months of monthly mail and telephone counseling and ( 2 ) a comparison condition addressing sun exposure protection . MAIN OUTCOME MEASURES Minutes per week of moderate plus vigorous PA measured by self-report and accelerometer ; self-report of days per week of PA and sedentary behaviors ; and percentage of energy from fat and servings per day of fruits and vegetables measured by three 24-hour diet recalls . Body mass index ( calculated as weight in kilograms divided by the square of height in meters ) was a secondary outcome . RESULTS Compared with adolescents in the sun protection condition , girls and boys in the diet and PA intervention significantly reduced sedentary behaviors ( intervention vs control change , 4.3 to 3.4 h/d vs 4.2 to 4.4 h/d for girls , respectively [ P = .001 ] ; 4.2 to 3.2 h/d vs 4.2 to 4.3 h/d for boys , respectively [ P = .001 ] ) . Boys reported more active days per week ( intervention vs control change : 4.1 to 4.4 d/wk vs 3.8 to 3.8 d/w , respectively [ P = .01 ] ) , and the number of servings of fruits and vegetables for girls approached significance ( intervention vs control change , 3.5 to 4.2 servings/d vs 3.5 to 3.9 servings/d , respectively [ P = .07 ] ) . No intervention effects were seen with percentage of calories from fat or minutes of PA per week . Percentage of adolescents meeting recommended health guidelines was significantly improved for girls for consumption of saturated fat ( intervention vs control change , 23.4 % to 41.0 % vs 18.5 % to 31 % , respectively [ relative risk , 1.33 ; 95 % confidence interval , 1.01 - 1.68 ] ) and for boys ' participation in d/wk of PA ( intervention vs control change , 45.3 % to 55.4 % vs 41.9 % to 38.0 % , respectively [ relative risk , 1.47 ; 95 % confidence interval , 1.19 - 1.75 ] ) . No between-group differences were seen in body mass index . CONCLUSIONS Improvements in some diet , PA , and sedentary behaviors in adolescents can be enabled through the use of a 1-year , integrated intervention using the computer , health provider counseling , mail , and telephone . The amount of intervention received may contribute to its efficacy BACKGROUND Prevention of childhood obesity is a public health priority . Parents influence a child 's weight by modeling healthy behaviors , controlling food availability and activity opportunities , and appropriate feeding practice s. Thus interventions should target education and behavioral change in the parent , and positive , mutually reinforcing behaviors within the family . METHODS This paper presents the design , rationale and baseline characteristics of Kids and Adults Now ! - Defeat Obesity ( KAN-DO ) , a r and omized controlled behavioral intervention trial targeting weight maintenance in children of healthy weight , and weight reduction in overweight children . 400 children aged 2 - 5 and their overweight or obese mothers in the Triangle and Triad regions of North Carolina are r and omized equally to control or the KAN-DO intervention , consisting of mailed family kits encouraging healthy lifestyle change . Eight ( monthly ) kits are supported by motivational counseling calls and a single group session . Mothers are targeted during a hypothesized " teachable moment " for health behavior change ( the birth of a new baby ) , and intervention content addresses : parenting skills ( ( e.g. , emotional regulation , authoritative parenting ) , healthy eating , and physical activity . RESULTS The 400 mother-child dyads r and omized to trial are 75 % white and 22 % black ; 19 % have a household income of $ 30,000 or below . At baseline , 15 % of children are overweight ( 85th-95th percentile for body mass index ) and 9 % are obese ( ≥ 95th percentile ) . CONCLUSION This intervention addresses childhood obesity prevention by using a family-based , synergistic approach , targeting at-risk children and their mothers during key transitional periods , and enhancing maternal self-regulation and responsive parenting as a foundation for health behavior change BACKGROUND This study tests the feasibility of an innovative school-based program for obesity prevention among adolescent girls . New Moves was implemented as a multicomponent , girls-only , high-school physical education class . METHODS Six schools were equally r and omized into intervention and control conditions . Data were collected at baseline , postintervention , and 8-month follow-up to assess program impact on physical activity , eating patterns , self-perceptions , and body mass index ( BMI ) among 89 girls in the intervention and 112 girls in the control conditions . Program evaluation also included interviews with school staff , parent surveys , and participant interviews and process evaluation surveys . RESULTS The feasibility of implementing New Moves was high , as indicated by strong satisfaction among participants , parents , and school staff , and by program sustainability . Participants perceived a positive program impact on their physical activity , eating patterns , and self-image . Girls in the intervention significantly progressed in their stage of behavioral change for physical activity from baseline to follow-up . However , for the majority of outcome variables , differences between intervention and control schools at postintervention and follow-up were not statistically significant . CONCLUSIONS New Moves was well received and fills a needed niche within school physical education programs . An exp and ed intervention and evaluation is needed to enhance and assess long-term program effectiveness OBJECTIVES To assess the impact of a culturally proficient dietary/physical activity intervention on changes in body mass index ( BMI ) ( kg/m 2 ) . STUDY DESIGN R and omized controlled trial ( Hip-Hop to Health Jr. ) conducted between September 1999 and June 2002 in 12 Head Start preschool programs in Chicago , Illinois . RESULTS Intervention children had significantly smaller increases in BMI compared with control children at 1-year follow-up , 0.06 vs 0.59 kg/m 2 ; difference -0.53 kg/m 2 ( 95 % CI -0.91 to -0.14 ) , P = .01 ; and at 2-year follow-up , 0.54 vs 1.08 kg/m 2 ; difference -0.54 kg/m 2 ( 95 % CI -0.98 to -0.10 ) , P = .02 , with adjustment for baseline age and BMI . The only significant difference between intervention and control children in food intake/physical activity was the Year 1 difference in percent of calories from saturated fat , 11.6 % vs 12.8 % ( P = .002 ) . CONCLUSIONS Hip-Hop to Health Jr. was effective in reducing subsequent increases in BMI in preschool children . This represents a promising approach to prevention of overweight among minority children in the preschool years Cardiovascular disease ( CVD ) is the number one cause of death in the United States . Obesity is highly related to CVD risk , especially in African American women . This study explored the efficacy of a culturally specific obesity prevention program . Design ed for low-income , inner-city African American girls and their mothers , the program addressed the importance of eating a low-fat , low-cholesterol diet and increasing activity . Mother-daughter dyads were r and omly assigned to a 12-week treatment or an attention placebo group . Participants were assessed at pre- and posttreatment on dietary intake , including daily fat intake , daily saturated fat intake , percentage of daily calories from fat , and daily cholesterol intake . Results showed significant differences between the treatment and control mothers for daily saturated fat intake and percentage of calories from fat . Differences among treatment and control groups were also noted for the daughters on percentage of daily calories from fat . Implication s of the findings for developing culturally specific health risk reduction programs are discussed The aim of the present study was to evaluate the effects of a middle school physical activity and healthy eating intervention , including an environmental and computer-tailored component , and to investigate the effects of parental involvement . A r and om sample of 15 schools with seventh and eight grade rs was r and omly assigned to one of three conditions : ( i ) intervention with parental involvement , ( ii ) intervention alone and ( iii ) control group . In 10 schools , an intervention , combining environmental changes with computer-tailored feedback , was implemented over 2 school years . In five intervention schools , increased parental support was added . Physical activity was measured with question naires in the total sample and with accelerometers in a sub- sample of children . Fat intake , fruit , water and soft drink consumption were measured using food-frequency question naires . Results showed significant positive intervention effects on physical activity in both genders and on fat intake in girls . Parental involvement did not increase intervention effects . It can be concluded that physical activity and eating behaviours of middle school children can be improved by school-based strategies combining environmental and personal interventions . The use of personalized computer-tailored interventions seems to be a promising tool for targeting adolescents but needs to be further explored BACKGROUND Weight-related problems are prevalent in adolescent girls . PURPOSE To evaluate New Moves , a school-based program aim ed at preventing weight-related problems in adolescent girls . DESIGN School-based group-r and omized controlled design . SETTING / PARTICIPANTS 356 girls ( mean age=15.8±1.2 years ) from six intervention and six control high schools . More than 75 % of the girls were racial/ethnic minorities and 46 % were overweight or obese . Data were collected in 2007 - 2009 and analyzed in 2009 - 2010 . INTERVENTION An all-girls physical education class , supplemented with nutrition and self-empowerment components , individual sessions using motivational interviewing , lunch meetings , and parent outreach . MAIN OUTCOME MEASURES Percentage body fat , BMI , physical activity , sedentary activity , dietary intake , eating patterns , unhealthy weight control behaviors , and body/self-image . RESULTS New Moves did not lead to significant changes in the girls ' percentage body fat or BMI but improvements were seen for sedentary activity , eating patterns , unhealthy weight control behaviors , and body/self-image . For example , in comparison to control girls , at 9-month follow-up , intervention girls decreased their sedentary behaviors by approximately one 30-minute block a day ( p=0.050 ) ; girls increased their portion control behaviors ( p=0.014 ) ; the percentage of girls using unhealthy weight control behaviors decreased by 13.7 % ( p=0.021 ) ; and improvements were seen in body image ( p=0.045 ) and self-worth ( p=0.031 ) . Additionally , intervention girls reported more support by friends , teachers , and families for healthy eating and physical activity . CONCLUSIONS New Moves provides a model for addressing the broad spectrum of weight-related problems among adolescent girls . Further work is needed to enhance the effectiveness of interventions to improve weight status of youth Abstract The study investigated the effect of a school-based healthy lifestyles intervention on physical activity and dietary variables . In total 378 children ( 177 intervention , 201 control ; age 9.75 ± 0.82 years ( mean ± s ) ) took part in the 7-month intervention comprising : preparation for and participation in 3 highlight events ( a dance festival , a walking event and a running event ) ; an interactive website for pupils , teachers and parents ; and vacation activity planners . Primary outcome measures were objective ly measured physical activity ( pedometers and accelerometers ) , endurance fitness and dietary variables . Multi-level modelling was employed for data analysis . The increase in physical activity was greater in the intervention group than the control group ( steps : 1049 vs 632 daily steps each month ; moderate to vigorous physical activity ( MVPA ) total : 4.6 min · day−1 · month−1 vs 1.3 min · day−1 · month−1 ; MVPA bouts : 5.4 min · day−1 · month−1 vs 2.6 min · day−1 · month−1 ; all P < 0.05 ) . The increase in multi-stage fitness test distance was greater for intervention participants ( 46 vs 29 m · month−1 of intervention , group × month interaction , P < 0.05 ) . There were no differences between groups in dietary variables , body composition , knowledge of healthy lifestyles or psychological variables . Thus an intervention centred around highlight events and including relatively few additional re sources can impact positively on the objective ly measured physical activity of children |
12,168 | 20,172,461 | There was insufficient evidence to draw conclusions about emotional and moral competence and ASRH .
Helping adolescents to achieve cognitive , social , and behavioral competence may reduce the likelihood of sexual activity and teen pregnancy , and increase contraceptive use . | To examine the association between " competence " and adolescent sexual and reproductive health ( ASRH ) outcomes .
Competence refers to the development of skills to perform tasks successfully in four areas including social and behavioral , cognitive , emotional , and moral competence . | Theories and empirical studies of adolescent sexual behavior have identified the contributions of personal attributes and social experiences ; however , it is rare that models have clarified developmental pathways to adolescent sexual behavior that include ( 1 ) factors assessed prior to and early in adolescence and ( 2 ) dyadic experiences in adolescence that provide the opportunity for sexual behavior ( i.e. , dating ) . Using data from a prospect i ve study , structural equation modeling was used to test a model predicting adolescent sexual behavior at age 19 , denoted by the number of lifetime sexual partners . Predictors examined were sociability and impulsivity assessed at 30 months of age , physical characteristics and experiences with peers measured at age 12–13 , the age of first romantic relationship , and frequency of alcohol use at age 16 . The pathway to greater sexual involvement was marked by some desired personal attributes ( e.g. , sociability ) and peer experiences ( e.g. , higher quality friendships ) . These associations were mediated , however , by earlier initiation of romantic relationships and more frequent use of alcohol in middle adolescence . Earlier initiation of romantic relationships and more frequent alcohol use were predicted by greater sociability and less impulsivity in childhood , higher quality friendships and greater peer acceptance in early adolescence , and a more mature appearance and physical attractiveness ( among females ) at age 13 . The findings imply a complex pathway that leads to a greater accumulation of sexual partners by age 19 . This pathway begins in childhood and includes individual qualities , peer acceptance , romantic relationships , and alcohol use CONTEXT Despite the recent declines in rates of teenage pregnancy , relatively little is known about the few programs that have been successful in reducing adolescent pregnancy . METHODS Six agencies in New York City each r and omly assigned 100 disadvantaged 13 - 15-year-olds to their usual youth program or to the intervention being tested -- the Children 's Aid Society-Carrera program , a year-round afterschool program with a comprehensive youth development orientation . Both program and control youth were followed for three years . Multivariate regression analyses assessed the effects of program participation on the odds of current sexual activity , use of a condom along with a hormonal contraceptive , pregnancy and access to good health care . RESULTS Seventy-nine percent of participants remained in the program for three full years . Female program participants had significantly lower odds than controls of being sexually active ( odds ratio , 0.5 ) and of having experienced a pregnancy ( 0.3 ) . They had significantly elevated odds of having used a condom and a hormonal method at last coitus ( 2.4 ) . However , participation in the program created no significant impact on males ' sexual and reproductive behavior outcomes . Nonetheless , program participants of both genders had elevated odds of having received good primary health care ( 2.0 - 2.1 ) . CONCLUSIONS This program is one of only four whose evaluation has successfully documented declines in teenage pregnancy using a r and om-assignment design . Better outcomes among males may be achieved if programs reach them even earlier than their teenage years OBJECTIVE To examine the long-term effects of the full Seattle Social Development Project intervention on sexual behavior and associated outcomes assessed at age 21 years . DESIGN Nonr and omized controlled trial with long-term follow-up . SETTING Public elementary schools serving children from high-crime areas in Seattle , Wash. PARTICIPANTS Ninety-three percent of the fifth- grade students enrolled in either the full-intervention or control group were successfully interviewed at age 21 years ( n = 144 [ full intervention ] and n = 205 [ control ] ) . INTERVENTIONS In-service teacher training , parenting classes , and social competence training for children . MAIN OUTCOME MEASURES Self-report measures of all outcomes . RESULTS The full-intervention group reported significantly fewer sexual partners and experienced a marginally reduced risk for initiating intercourse by age 21 years as compared with the control group . Among females , treatment group status was associated with a significantly reduced likelihood of both becoming pregnant and experiencing a birth by age 21 years . Among single individuals , a significantly increased probability of condom use during last intercourse was predicted by full-intervention group membership ; a significant ethnic group x intervention group interaction indicated that after controlling for socioeconomic status , single African Americans were especially responsive to the intervention in terms of this outcome . Finally , a significant treatment x ethnic group interaction indicated that among African Americans , being in the full-intervention group predicted a reduced probability of contracting a sexually transmitted disease by age 21 years . CONCLUSION A theory-based social development program that promotes academic success , social competence , and bonding to school during the elementary grade s can prevent risky sexual practice s and adverse health consequences in early adulthood Background Spanish-dominant Latino youth represent a growing yet underserved segment of the U.S. population , especially in terms of protection from sexually transmitted HIV infection . There is evidence to suggest that this subgroup engages in both risk and protective behaviors that may be different from the behaviors of English-dominant Latino youth . Objective To examine theoretical predictors ( attitude , subjective norm , behavioral beliefs , normative beliefs , control beliefs ) of sexual intercourse and condom use with a sample of Spanish-dominant Latino youth . Methods Participants in this study were part of a larger r and omized controlled intervention design ed to reduce the risk of sexually transmitted HIV among Latino youth . This article is based on preintervention data from 141 Spanish-speaking Latino adolescents ( 77 girls and 64 boys ) who completed a Spanish version of the question naire . Results Multiple regression analyses showed significant effects of attitudes , perceived partner approval , self-pride , and parental pride on intentions to engage in sexual intercourse . Attitudes , intentions to engage in sex in the next 3 months , self-pride , parental pride , goals , and partner approval predicted sexual intercourse in the preceding 3 months . Attitudes , subjective norms , self-efficacy , partner and parental approval , and impulse control beliefs were significant predictors of intentions to use condoms . Conclusions This study represents initial efforts to address the needs of Spanish-dominant Latino youth . The identification of salient beliefs that may predict sexual risk and protective behavior are relevant to the design of culturally and linguistically effective interventions OBJECTIVE African-American adolescents living in high-risk inner-city environments have been disproportionately affected by the epidemics of human immunodeficiency virus ( HIV ) and other sexually transmitted diseases . Underst and ing the factors that influence the use of condoms by adolescents is critical for developing effective behavioral interventions . The present study examined the demographic , psychosocial , and behavioral correlates of condom use among African-American adolescents residing in public housing developments in an HIV epicenter ( San Francisco ) and prospect ively evaluated the stability of these significant cross-sectional variables to predict consistent condom use . DESIGN A prospect i ve study . SETTING Two public housing developments in San Francisco . PARTICIPANTS African-American adolescents and young adults between 12 and 21 years of age were recruited though street outreach and completed a theoretically derived research interview assessing HIV-related knowledge , attitudes , and behaviors . After a 6-month period , adolescents completed a follow-up interview similar to the baseline measure . Among adolescents reporting sexual activity in the 6 months before completing the baseline interview ( n = 116 ) , logistic regression analysis evaluated the influence of demographic , psychosocial , and behavioral factors on consistent condom use . RESULTS Adolescents who had high assertive self-efficacy to dem and condom use ( adjusted odds ratio [ OR ] , 11 ) , perceived peer norms as supporting condom use ( OR , 4.2 ) , had greater impulse control ( OR , 3.7 ) , were male ( OR , 4.7 ) , and were younger ( OR , 2.9 ) were more likely to report consistent condom use . Frequency of sexual intercourse was inversely related to condom use ; adolescents with higher numbers of sexual episodes were less likely to use condoms consistently . Prospect i ve analyses identified the baseline level of condom use as the best predictor of condom use at the 6-month follow-up . Adolescents who were consistent condom users at baseline were 7.4 times as likely to be consistent condom users during the follow-up period . Of those adolescents changing their frequency of condom use during the follow-up interval , significantly more engaged in risky behavior ; 33.3 % changed from consistent to inconsistent condom use , whereas 20.6 % changed from inconsistent to consistent use ( OR , 1.6 ) . CONCLUSIONS The findings suggest that HIV prevention programs need to be implemented early , before high-risk behaviors are established and may be more difficult to modify To estimate trends and determinants of sexual initiation and contraceptive use among adolescent women in Northeast Brazil , multivariate logistic hazard models are used that draw on data from three Demographic and Health Surveys conducted there between 1986 and 1996 . Educational attainment is among the variables found to be associated most consistently with differential risk of engaging in first intercourse during adolescence , including premarital intercourse , and of contraceptive use during sexual initiation . Greater frequency of attending religious services and greater exposure to television are also associated with lower rates of sexual initiation and higher use of contraceptives . Seemingly diminishing returns of education on delayed sexual activity may help explain , in part , observed increases in the absolute level of adolescent sexual experience across survey periods , however . Multilevel modeling techniques pointing to the existence of cluster-level r and om variances underline the need for further research into community influences on individual sexual activity 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 OBJECTIVES We sought to test the efficacy of an intervention that was design ed to promote social inclusion and commitment to education , in reducing among students health risk behaviors and improving emotional well-being . METHODS The design was a cluster-r and omized trial in 25 secondary schools in Victoria , Australia . The subjects were 8th- grade students ( aged 13 to 14 y ) in 1997 ( n=2545 ) and subsequent 8th- grade students in 1999 ( n=2586 ) and 2001 ( n=2463 ) . The main outcomes were recent substance use , antisocial behavior , initiation of sexual intercourse , and depressive symptoms . RESULTS At 4-year follow-up , the prevalence of marked health risk behaviors was approximately 20 % in schools in the comparison group and 15 % in schools in the intervention group , an overall reduction of 25 % . In ordinal logistic regression models a protective effect of intervention was found for a composite measure of health risk behaviors in unadjusted models ( odds ratio [OR]= 0.69 ; 95 % confidence interval [CI]= 0.50 , 0.95 ) and adjusted models ( OR= 0.71 ; CI = 0.52 , 0.97 ) for potential confounders . There was no evidence of a reduction in depressive symptoms . CONCLUSION The study provides support for prevention strategies in schools that move beyond health education to promoting positive social environments Condom promotion strategies for adolescents typically include provision of STD/HIV-associated knowledge , fostering favorable attitudes toward condom use , promoting positive peer norms regarding condom use , improving condom-related communication skills and self-efficacy , and overcoming barriers to condom use . The purpose of this study was to identify which of these constructs were prospect ively associated with condom use among a high-risk sample of African American adolescent females reporting sexual activity with a steady male partner . Adolescents , 14–18 years old , were recruited from schools and health clinics . Adolescents completed an in-depth survey and interview at baseline and again 6 months later . Analyses were limited to adolescents with steady partners who reported sexual activity between the baseline and 6-month follow-up assessment periods ( N = 179 ) . At baseline , five-scale measures and a single-item measure were used to assess predictive constructs . At follow-up , adolescents were asked about their frequency of condom use over various periods of recall . Multivariate models were created to control for the confounding influence of pregnancy status . The findings were remarkably distinct . The evidence strongly supported the predictive role of perceived barriers toward condom use and peer norms . The measure of sexual communication achieved significance for two of the six assessed outcomes . Alternatively , measures of attitudes toward condom use , condom negotiation self-efficacy , and knowledge about STD/HIV-prevention were consistently nonsignificant . The findings suggest that to improve effectiveness of individual-level STD/HIV prevention programs , design ed for this population , program emphasis should be on reducing barriers to condom use , teaching partner communication skills , and fostering positive peer norms relevant to condom use Predictive effects of school experiences were studied over a 7-year interval in a r and om community sample of 452 adolescents , 12 through 18 years of age . Outcomes examined included dropping out of school , adolescent pregnancy , engaging in criminal activities , criminal conviction , antisocial personality disorder , and alcohol abuse . Logistic regression showed academic achievement , academic aspirations , and leaming-focused school setting s to be related to a decline in deviant outcomes independent of the effects of disadvantaged socioeconomic background , low intelligence , childhood conduct problems , and having deviant friends during adolescence . Associations between school conflict and later deviancy were mediated by deviant peer relationships in adolescence and other school characteristics . Prior research reporting continuity of childhood conduct problems and the influence of adolescent affiliations with deviant peers on negative outcomes was supported . Implication sfor using the school context in riskfactor research and the practical applications of such research for intervention are discussed A six-month prospect i ve study examined consistency of condom use for disease prevention among 308 adolescent women who had received a prescription for oral contraceptives at a family planning clinic . Only 16 percent used condoms consistently over a six-month period , yet 30 percent were considered at high risk for sexually transmitted diseases ( STDs ) because of multiple , sequential or concurrent relationships with male partners . The type of relationship in which the adolescents were involved did not predict consistency of condom use . Consistent condom use was associated with having asked a partner to use a condom , perceiving partner support for condom use , having less frequent sexual intercourse and using oral contraceptives inconsistently . The findings suggest that family planning providers need to more strongly emphasize to adolescents the importance of consistent condom use to protect against STD infection A developmental framework emphasizing the combined impact of correlated constraints within and without the individual was applied to a prospect i ve longitudinal study of early parenthood . The purpose was to use a person-approach to the analysis of longitudinal data to clarify risk for early parenthood and to generate hypotheses about potentially useful intervention strategies . Respondents were 475 youth who were assessed annually from seventh grade through the end of high school and , again , at ages 20 and 24 . The risk patterns associated with parenthood were the same for both sexes . Individuals with a middle-school configuration of low socioeconomic status , high aggression , low academic skills , low popularity , and prior grade failure were most likely to become parents by early adulthood . Risk for early parenthood increased substantially for respondents who dropped out of school early , regardless of their initial risk status Longitudinal data from a representative sample of 1,978 Black and White adolescents were used to examine the role of personality in multiple risk or problem behaviors . Results indicate that covariation among diverse behaviors ( educational underachievement , delinquent behavior , substance use , sexual behavior ) can be adequately modeled by a single higher order factor , and that impulsivity and avoidance coping serve as generalized risk factors for involvement in these behaviors . Whereas none of the personality variables examined explained change in problem behaviors once established , avoidance coping prospect ively predicted involvement among a subgroup of adolescents with little or no prior involvement . Results suggest that dysfunctional styles of regulating emotions and emotionally driven behaviors are core features of risky or problem behaviors during adolescence |
12,169 | 27,091,337 | In pooled analysis endovascular treatment , including thrombectomy , was associated with a higher proportion of patients experiencing good ( modified Rankin scale scores ≤2 ) and excellent ( scores ≤1 ) outcomes 90 days after stroke , without differences in mortality or rates for symptomatic intracranial haemorrhage , compared with patients r and omised to medical care alone , including intravenous rt-PA .
The more recent studies ( seven r and omised controlled trials , published or presented in 2015 ) proved better suited to evaluate the effect of adjunctive intra-arterial mechanical thrombectomy on its index disease owing to more accurate patient selection , intravenous rt-PA being administered at a higher rate and earlier , and the use of more efficient thrombectomy devices .
Moderate to high quality evidence suggests that compared with medical care alone in a selected group of patients endovascular thrombectomy as add-on to intravenous thrombolysis performed within six to eight hours after large vessel ischaemic stroke in the anterior circulation provides beneficial functional outcomes , without increased detrimental effects . | OBJECTIVES To evaluate the efficacy and safety of endovascular treatment , particularly adjunctive intra-arterial mechanical thrombectomy , in patients with ischaemic stroke . | BACKGROUND In patients with ischemic stroke , endovascular treatment results in a higher rate of recanalization of the affected cerebral artery than systemic intravenous thrombolytic therapy . However , comparison of the clinical efficacy of the two approaches is needed . METHODS We r and omly assigned 362 patients with acute ischemic stroke , within 4.5 hours after onset , to endovascular therapy ( intraarterial thrombolysis with recombinant tissue plasminogen activator [ t-PA ] , mechanical clot disruption or retrieval , or a combination of these approaches ) or intravenous t-PA . Treatments were to be given as soon as possible after r and omization . The primary outcome was survival free of disability ( defined as a modified Rankin score of 0 or 1 on a scale of 0 to 6 , with 0 indicating no symptoms , 1 no clinical ly significant disability despite symptoms , and 6 death ) at 3 months . RESULTS A total of 181 patients were assigned to receive endovascular therapy , and 181 intravenous t-PA . The median time from stroke onset to the start of treatment was 3.75 hours for endovascular therapy and 2.75 hours for intravenous t-PA ( P<0.001 ) . At 3 months , 55 patients in the endovascular-therapy group ( 30.4 % ) and 63 in the intravenous t-PA group ( 34.8 % ) were alive without disability ( odds ratio adjusted for age , sex , stroke severity , and atrial fibrillation status at baseline , 0.71 ; 95 % confidence interval , 0.44 to 1.14 ; P=0.16 ) . Fatal or nonfatal symptomatic intracranial hemorrhage within 7 days occurred in 6 % of the patients in each group , and there were no significant differences between groups in the rates of other serious adverse events or the case fatality rate . CONCLUSIONS The results of this trial in patients with acute ischemic stroke indicate that endovascular therapy is not superior to st and ard treatment with intravenous t-PA . ( Funded by the Italian Medicines Agency , Clinical Trials.gov number , NCT00640367 . ) Background Endovascular or intra-arterial treatment ( IAT ) increases the likelihood of recanalization in patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion . However , a beneficial effect of IAT on functional recovery in patients with acute ischemic stroke remains unproven . The aim of this study is to assess the effect of IAT on functional outcome in patients with acute ischemic stroke . Additionally , we aim to assess the safety of IAT , and the effect on recanalization of different mechanical treatment modalities . Methods / design A multicenter r and omized clinical trial with blinded outcome assessment . The active comparison is IAT versus no IAT . IAT may consist of intra-arterial thrombolysis with alteplase or urokinase , mechanical treatment or both . Mechanical treatment refers to retraction , aspiration , sonolysis , or use of a retrievable stent ( stent-retriever ) . Patients with a relevant intracranial proximal arterial occlusion of the anterior circulation , who can be treated within 6 hours after stroke onset , are eligible . Treatment effect will be estimated with ordinal logistic regression ( shift analysis ) ; 500 patients will be included in the trial for a power of 80 % to detect a shift leading to a decrease in dependency in 10 % of treated patients . The primary outcome is the score on the modified Rankin scale at 90 days . Secondary outcomes are the National Institutes of Health stroke scale score at 24 hours , vessel patency at 24 hours , infa rct size on day 5 , and the occurrence of major bleeding during the first 5 days . Discussion If IAT leads to a 10 % absolute reduction in poor outcome after stroke , careful implementation of the intervention could save approximately 1 % of all new stroke cases from death or disability annually . Trial registration NTR1804 ( 7 May 2009)/IS RCT N10888758 ( 24 July 2012 ) BACKGROUND Trials of endovascular therapy for ischemic stroke have produced variable results . We conducted this study to test whether more advanced imaging selection , recently developed devices , and earlier intervention improve outcomes . METHODS We r and omly assigned patients with ischemic stroke who were receiving 0.9 mg of alteplase per kilogram of body weight less than 4.5 hours after the onset of ischemic stroke either to undergo endovascular thrombectomy with the Solitaire FR ( Flow Restoration ) stent retriever or to continue receiving alteplase alone . All the patients had occlusion of the internal carotid or middle cerebral artery and evidence of salvageable brain tissue and ischemic core of less than 70 ml on computed tomographic ( CT ) perfusion imaging . The co primary outcomes were reperfusion at 24 hours and early neurologic improvement ( ≥8-point reduction on the National Institutes of Health Stroke Scale or a score of 0 or 1 at day 3 ) . Secondary outcomes included the functional score on the modified Rankin scale at 90 days . RESULTS The trial was stopped early because of efficacy after 70 patients had undergone r and omization ( 35 patients in each group ) . The percentage of ischemic territory that had undergone reperfusion at 24 hours was greater in the endovascular-therapy group than in the alteplase-only group ( median , 100 % vs. 37 % ; P<0.001 ) . Endovascular therapy , initiated at a median of 210 minutes after the onset of stroke , increased early neurologic improvement at 3 days ( 80 % vs. 37 % , P=0.002 ) and improved the functional outcome at 90 days , with more patients achieving functional independence ( score of 0 to 2 on the modified Rankin scale , 71 % vs. 40 % ; P=0.01 ) . There were no significant differences in rates of death or symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with ischemic stroke with a proximal cerebral arterial occlusion and salvageable tissue on CT perfusion imaging , early thrombectomy with the Solitaire FR stent retriever , as compared with alteplase alone , improved reperfusion , early neurologic recovery , and functional outcome . ( Funded by the Australian National Health and Medical Research Council and others ; EXTEND-IA Clinical Trials.gov number , NCT01492725 , and Australian New Zeal and Clinical Trials Registry number , ACTRN12611000969965 . ) Rationale Multimodal imaging has the potential to identify acute ischaemic stroke patients most likely to benefit from late recanalization therapies . Aims The general aim of the Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy Trial is to investigate whether multimodal imaging can identify patients who will benefit substantially from mechanical embolectomy for the treatment of acute ischaemic stroke up to eight-hours from symptom onset . Design Mechanical Retrieval and Recanalization of Stroke Clots Using Embolectomy is a r and omized , controlled , blinded- outcome clinical trial . Population studied Acute ischaemic stroke patients with large vessel intracranial internal carotid artery or middle cerebral artery M1 or M2 occlusion enrolled within eight-hours of symptom onset are eligible . The study sample size is 120 patients . Study intervention Patients are r and omized to endovascular embolectomy employing the Merci Retriever ( Concentric Medical , Mountain View , CA ) or the Penumbra System ( Penumbra , Alameda , CA ) vs. st and ard medical care , with r and omization stratified by penumbral pattern . Outcomes The primary aim of the trial is to test the hypothesis that the presence of substantial ischaemic penumbral tissue visualized on multimodal imaging ( magnetic resonance imaging or computed tomography ) predicts patients most likely to respond to mechanical embolectomy for treatment of acute ischaemic stroke due to a large vessel , intracranial occlusion up to eight-hours from symptom onset . This hypothesis will be tested by analysing whether pretreatment imaging pattern has a significant interaction with treatment as a determinant of functional outcome based on the distribution of scores on the modified Rankin Scale measure of global disability assessed 90 days poststroke . Nested hypotheses test for ( 1 ) treatment efficacy in patients with a penumbral pattern pretreatment , and ( 2 ) absence of treatment benefit ( equivalency ) in patients without a penumbral pattern pretreatment . An additional aim will only be tested if the primary hypothesis of an interaction is negative : that patients treated with mechanical embolectomy have improved functional outcome vs. st and ard medical management ESCAPE is a prospect i ve , multicenter , r and omized clinical trial that will enroll subjects with the following main inclusion criteria : less than 12 h from symptom onset , age > 18 , baseline NIHSS > 5 , ASPECTS score of > 5 and CTA evidence of carotid T/L or M1 segment MCA occlusion , and at least moderate collaterals by CTA . The trial will determine if endovascular treatment will result in higher rates of favorable outcome compared with st and ard medical therapy alone . Patient population s that are eligible include those receiving IV tPA , tPA ineligible and unwitnessed onset or wake up strokes with 12 h of last seen normal . The primary end-point , based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days assessed using a proportional odds model . The projected maximum sample size is 500 subjects . R and omization is stratified under a minimization process using age , gender , baseline NIHSS , baseline ASPECTS ( 8–10 vs. 6–7 ) , IV tPA treatment and occlusion location ( ICA vs. MCA ) as covariates . The study will have one formal interim analysis after 300 subjects have been accrued . Secondary end-points at 90 days include the following : mRS 0–1 ; mRS 0–2 ; Barthel 95–100 , EuroQOL and a cognitive battery . Safety outcomes are symptomatic ICH , major bleeding , contrast nephropathy , total radiation dose , malignant MCA infa rct ion , hemicraniectomy and mortality at 90 days BACKGROUND We aim ed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population -based stroke reperfusion registry . METHODS During a 2-year period at four centers in Catalonia , Spain , we r and omly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy ( including intravenous alteplase when eligible ) and endovascular therapy with the Solitaire stent retriever ( thrombectomy group ) or medical therapy alone ( control group ) . All patients had confirmed proximal anterior circulation occlusion and the absence of a large infa rct on neuroimaging . In all study patients , the use of alteplase either did not achieve revascularization or was contraindicated . The primary outcome was the severity of global disability at 90 days , as measured on the modified Rankin scale ( ranging from 0 [ no symptoms ] to 6 [ death ] ) . Although the maximum planned sample size was 690 , enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials . RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale ( adjusted odds ratio for improvement of 1 point , 1.7 ; 95 % confidence interval [ CI ] , 1.05 to 2.8 ) and led to higher rates of functional independence ( a score of 0 to 2 ) at 90 days ( 43.7 % vs. 28.2 % ; adjusted odds ratio , 2.1 ; 95 % CI , 1.1 to 4.0 ) . At 90 days , the rates of symptomatic intracranial hemorrhage were 1.9 % in both the thrombectomy group and the control group ( P=1.00 ) , and rates of death were 18.4 % and 15.5 % , respectively ( P=0.60 ) . Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals . CONCLUSIONS Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset , stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence . ( Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others ; REVASCAT Clinical Trials.gov number , NCT01692379 . ) BACKGROUND Among patients with acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , less than 40 % regain functional independence when treated with intravenous tissue plasminogen activator ( t-PA ) alone . Thrombectomy with the use of a stent retriever , in addition to intravenous t-PA , increases reperfusion rates and may improve long-term functional outcome . METHODS We r and omly assigned eligible patients with stroke who were receiving or had received intravenous t-PA to continue with t-PA alone ( control group ) or to undergo endovascular thrombectomy with the use of a stent retriever within 6 hours after symptom onset ( intervention group ) . Patients had confirmed occlusions in the proximal anterior intracranial circulation and an absence of large ischemic-core lesions . The primary outcome was the severity of global disability at 90 days , as assessed by means of the modified Rankin scale ( with scores ranging from 0 [ no symptoms ] to 6 [ death ] ) . RESULTS The study was stopped early because of efficacy . At 39 centers , 196 patients underwent r and omization ( 98 patients in each group ) . In the intervention group , the median time from qualifying imaging to groin puncture was 57 minutes , and the rate of substantial reperfusion at the end of the procedure was 88 % . Thrombectomy with the stent retriever plus intravenous t-PA reduced disability at 90 days over the entire range of scores on the modified Rankin scale ( P<0.001 ) . The rate of functional independence ( modified Rankin scale score , 0 to 2 ) was higher in the intervention group than in the control group ( 60 % vs. 35 % , P<0.001 ) . There were no significant between-group differences in 90-day mortality ( 9 % vs. 12 % , P=0.50 ) or symptomatic intracranial hemorrhage ( 0 % vs. 3 % , P=0.12 ) . CONCLUSIONS In patients receiving intravenous t-PA for acute ischemic stroke due to occlusions in the proximal anterior intracranial circulation , thrombectomy with a stent retriever within 6 hours after onset improved functional outcomes at 90 days . ( Funded by Covidien ; SWIFT PRIME Clinical Trials.gov number , NCT01657461 . ) BACKGROUND Among patients with a proximal vessel occlusion in the anterior circulation , 60 to 80 % of patients die within 90 days after stroke onset or do not regain functional independence despite alteplase treatment . We evaluated rapid endovascular treatment in addition to st and ard care in patients with acute ischemic stroke with a small infa rct core , a proximal intracranial arterial occlusion , and moderate-to-good collateral circulation . METHODS We r and omly assigned participants to receive st and ard care ( control group ) or st and ard care plus endovascular treatment with the use of available thrombectomy devices ( intervention group ) . Patients with a proximal intracranial occlusion in the anterior circulation were included up to 12 hours after symptom onset . Patients with a large infa rct core or poor collateral circulation on computed tomography ( CT ) and CT angiography were excluded . Workflow times were measured against predetermined targets . The primary outcome was the score on the modified Rankin scale ( range , 0 [ no symptoms ] to 6 [ death ] ) at 90 days . A proportional odds model was used to calculate the common odds ratio as a measure of the likelihood that the intervention would lead to lower scores on the modified Rankin scale than would control care ( shift analysis ) . RESULTS The trial was stopped early because of efficacy . At 22 centers worldwide , 316 participants were enrolled , of whom 238 received intravenous alteplase ( 120 in the intervention group and 118 in the control group ) . In the intervention group , the median time from study CT of the head to first reperfusion was 84 minutes . The rate of functional independence ( 90-day modified Rankin score of 0 to 2 ) was increased with the intervention ( 53.0 % , vs. 29.3 % in the control group ; P<0.001 ) . The primary outcome favored the intervention ( common odds ratio , 2.6 ; 95 % confidence interval , 1.7 to 3.8 ; P<0.001 ) , and the intervention was associated with reduced mortality ( 10.4 % , vs. 19.0 % in the control group ; P=0.04 ) . Symptomatic intracerebral hemorrhage occurred in 3.6 % of participants in intervention group and 2.7 % of participants in control group ( P=0.75 ) . CONCLUSIONS Among patients with acute ischemic stroke with a proximal vessel occlusion , a small infa rct core , and moderate-to-good collateral circulation , rapid endovascular treatment improved functional outcomes and reduced mortality . ( Funded by Covidien and others ; ESCAPE Clinical Trials.gov number , NCT01778335 . ) BACKGROUND In patients with acute ischemic stroke caused by a proximal intracranial arterial occlusion , intraarterial treatment is highly effective for emergency revascularization . However , proof of a beneficial effect on functional outcome is lacking . METHODS We r and omly assigned eligible patients to either intraarterial treatment plus usual care or usual care alone . Eligible patients had a proximal arterial occlusion in the anterior cerebral circulation that was confirmed on vessel imaging and that could be treated intraarterially within 6 hours after symptom onset . The primary outcome was the modified Rankin scale score at 90 days ; this categorical scale measures functional outcome , with scores ranging from 0 ( no symptoms ) to 6 ( death ) . The treatment effect was estimated with ordinal logistic regression as a common odds ratio , adjusted for prespecified prognostic factors . The adjusted common odds ratio measured the likelihood that intraarterial treatment would lead to lower modified Rankin scores , as compared with usual care alone ( shift analysis ) . RESULTS We enrolled 500 patients at 16 medical centers in The Netherl and s ( 233 assigned to intraarterial treatment and 267 to usual care alone ) . The mean age was 65 years ( range , 23 to 96 ) , and 445 patients ( 89.0 % ) were treated with intravenous alteplase before r and omization . Retrievable stents were used in 190 of the 233 patients ( 81.5 % ) assigned to intraarterial treatment . The adjusted common odds ratio was 1.67 ( 95 % confidence interval [ CI ] , 1.21 to 2.30 ) . There was an absolute difference of 13.5 percentage points ( 95 % CI , 5.9 to 21.2 ) in the rate of functional independence ( modified Rankin score , 0 to 2 ) in favor of the intervention ( 32.6 % vs. 19.1 % ) . There were no significant differences in mortality or the occurrence of symptomatic intracerebral hemorrhage . CONCLUSIONS In patients with acute ischemic stroke caused by a proximal intracranial occlusion of the anterior circulation , intraarterial treatment administered within 6 hours after stroke onset was effective and safe . ( Funded by the Dutch Heart Foundation and others ; MR CLEAN Netherl and s Trial Registry number , NTR1804 , and Current Controlled Trials number , IS RCT N10888758 . ) BACKGROUND The aim of the Safe Implementation of Thrombolysis in Stroke-Monitoring Study ( SITS-MOST ) was to assess the safety and efficacy of intravenous alteplase as thrombolytic therapy within the first 3 h of onset of acute ischaemic stroke . Under European Union regulations , SITS-MOST was required to assess the safety profile of alteplase in clinical practice by comparison with results in r and omised controlled trials . METHODS 6483 patients were recruited from 285 centres ( 50 % with little previous experience in stroke thrombolysis ) in 14 countries between 2002 and 2006 for this prospect i ve , open , monitored , observational study . Primary outcomes were symptomatic ( a deterioration in National Institutes of Health stroke scale score of > or=4 ) intracerebral haemorrhage type 2 within 24 h and mortality at 3 months . We compared mortality , the proportion of patients with symptomatic intracerebral haemorrhage as per the Cochrane definition , and functional outcome at 3 months with relevant pooled results from r and omised controlled trials . FINDINGS Baseline characteristics of patients in SITS-MOST were much the same as those in the pooled r and omised controlled trials . At 24 h , the proportion of patients with symptomatic intracerebral haemorrhage ( per the SITS-MOST protocol ) was 1.7 % ( 107/6444 ; 95 % CI 1.4 - 2.0 ) ; at 7 days , the proportion with the same condition as per the Cochrane definition was 7.3 % ( 468/6438 ; 6.7 - 7.9 ) compared with 8.6 % ( 40/465 ; 6.3 - 11.6 ) in the pooled r and omised controlled trials . The mortality rate at 3 months in SITS-MOST was 11.3 % ( 701/6218 ; 10.5 - 12.1 ) compared with 17.3 % ( 83/479 ; 14.1 - 21.1 ) in the pooled r and omised controlled trials . INTERPRETATION These data confirm that intravenous alteplase is safe and effective in routine clinical use when used within 3 h of stroke onset , even by centres with little previous experience of thrombolytic therapy for acute stroke . The findings should encourage wider use of thrombolytic therapy for suitable patients treated in stroke centres BACKGROUND Whether brain imaging can identify patients who are most likely to benefit from therapies for acute ischemic stroke and whether endovascular thrombectomy improves clinical outcomes in such patients remains unclear . METHODS In this study , we r and omly assigned patients within 8 hours after the onset of large-vessel , anterior-circulation strokes to undergo mechanical embolectomy ( Merci Retriever or Penumbra System ) or receive st and ard care . All patients underwent pretreatment computed tomography or magnetic resonance imaging of the brain . R and omization was stratified according to whether the patient had a favorable penumbral pattern ( substantial salvageable tissue and small infa rct core ) or a nonpenumbral pattern ( large core or small or absent penumbra ) . We assessed outcomes using the 90-day modified Rankin scale , ranging from 0 ( no symptoms ) to 6 ( dead ) . RESULTS Among 118 eligible patients , the mean age was 65.5 years , the mean time to enrollment was 5.5 hours , and 58 % had a favorable penumbral pattern . Revascularization in the embolectomy group was achieved in 67 % of the patients . Ninety-day mortality was 21 % , and the rate of symptomatic intracranial hemorrhage was 4 % ; neither rate differed across groups . Among all patients , mean scores on the modified Rankin scale did not differ between embolectomy and st and ard care ( 3.9 vs. 3.9 , P=0.99 ) . Embolectomy was not superior to st and ard care in patients with either a favorable penumbral pattern ( mean score , 3.9 vs. 3.4 ; P=0.23 ) or a nonpenumbral pattern ( mean score , 4.0 vs. 4.4 ; P=0.32 ) . In the primary analysis of scores on the 90-day modified Rankin scale , there was no interaction between the pretreatment imaging pattern and treatment assignment ( P=0.14 ) . CONCLUSIONS A favorable penumbral pattern on neuroimaging did not identify patients who would differentially benefit from endovascular therapy for acute ischemic stroke , nor was embolectomy shown to be superior to st and ard care . ( Funded by the National Institute of Neurological Disorders and Stroke ; MR RESCUE Clinical Trials.gov number , NCT00389467 . ) Rationale Early reperfusion in patients experiencing acute ischemic stroke is critical , especially for patients with large vessel occlusion who have poor prognosis without revascularization . Solitaire ™ stent retriever devices have been shown to immediately restore vascular perfusion safely , rapidly , and effectively in acute ischemic stroke patients with large vessel occlusions . Aim The aim of the study was to demonstrate that , among patients with large vessel , anterior circulation occlusion who have received intravenous tissue plasminogen activator , treatment with Solitaire revascularization devices reduces degree of disability 3 months post stroke . Design The study is a global multicenter , two-arm , prospect i ve , r and omized , open , blinded end-point trial comparing functional outcomes in acute ischemic stroke patients who are treated with either intravenous tissue plasminogen activator alone or intravenous tissue plasminogen activator in combination with the Solitaire device . Up to 833 patients will be enrolled . Procedures Patients who have received intravenous tissue plasminogen activator are r and omized to either continue with intravenous tissue plasminogen activator alone or additionally proceed to neurothrombectomy using the Solitaire device within six-hours of symptom onset . Study Outcomes The primary end-point is 90-day global disability , assessed with the modified Rankin Scale ( mRS ) . Secondary outcomes include mortality at 90 days , functional independence ( mRS ≤ 2 ) at 90 days , change in National Institutes of Health Stroke Scale at 27 h , reperfusion at 27 h , and thrombolysis in cerebral infa rct ion 2b/3 flow at the end of the procedure . Analysis Statistical analysis will be conducted using simultaneous success criteria on the overall distribution of modified Rankin Scale ( Rankin shift ) and proportions of subjects achieving functional independence ( mRS 0–2 ) Rationale Reperfusion in ischemic stroke can be pursued by either systemic intravenous thrombolysis or endovascular treatment . However , systemic intravenous thrombolysis with alteplase within 4·5 h of symptom onset in selected patients is the only medication of proven efficacy . No r and omized-controlled trials have so far compared the two modalities . To explore this , after a pilot phase , we started the SYNTHESIS Expansion trial . Aims To determine whether endovascular treatment ( i.e. , intra-arterial thrombolysis with alteplase – if necessary , associated to or substituted by mechanical clot disruption and /or retrieval ) compared with systemic intravenous thrombolysis with alteplase , administered according to European labelling , increases the proportion of independent survivors at three-months . Design SYNTHESIS Expansion is an open-label , multicenter r and omized-controlled trial , with blinded follow-up . Eligibility applies to ; patients with symptomatic ischemic stroke , seen within 4·5 h of onset ; being able to initiate intravenous alteplase immediately , and endovascular treatment as soon as possible ( not later than six-hours of stroke onset ) . The study is pragmatically based on the ‘ uncertainty principle ’ between endovascular treatment and systemic intravenous thrombolysis for patients eligible for intravenous alteplase . There are no prespecified clinical or instrumental criteria to further select a patient , although investigators are left free to use them . Enrollment will be completed with 350 r and omized patients . Primary analysis is on an intent-to-treat basis . Study outcomes Primary : modified Rankin scale score of 0 or 1 at three-months . Secondary : neurological deficit seven-days after thrombolysis and the safety of the procedure on the basis of events reported within seven-days following thrombolysis – symptomatic cerebral hemorrhage , fatal and nonfatal stroke , death from any cause , neurological deterioration BACKGROUND The Solitaire Flow Restoration Device is a novel , self-exp and ing stent retriever design ed to yield rapid flow restoration in acute cerebral ischaemia . We compared the efficacy and safety of Solitaire with the st and ard , predicate mechanical thrombectomy device , the Merci Retrieval System . METHODS In this r and omised , parallel-group , non-inferiority trial , we enrolled patients from 18 sites ( 17 in the USA and one in France ) . Patients were eligible for inclusion if they had acute ischaemic stroke with moderate to severe neurological deficits and were treatable by thrombectomy within 8 h of stroke symptom onset . We used a computer-generated r and omisation sequence to r and omly allocate patients to receive thrombectomy treatment with either Solitaire or Merci ( 1:1 ; block sizes of four and stratified by centre and stroke severity ) . The primary endpoint was Thrombolysis In Myocardial Ischemia ( TIMI ) scale 2 or 3 flow in all treatable vessels without symptomatic intracranial haemorrhage , after up to three passes of the assigned device , as assessed by an independent core laboratory , which was masked to study assignment . Primary analysis was done by intention to treat . A prespecified efficacy stopping rule triggered an early halt to the trial . The study is registered with Clinical Trials.gov , number NCT 01054560 . RESULTS Between February , 2010 , and February , 2011 , we r and omly allocated 58 patients to the Solitaire group and 55 patients to the Merci group . The primary efficacy outcome was achieved more often in the Solitaire group than it was in the Merci group ( 61%vs 24 % ; difference 37 % [ 95 % CI 19 - 53 ] , odds ratio [ OR ] 4·87 [ 95 % CI 2·14 - 11·10 ] ; p(non-inferiority)<0·0001 , p(superiority)=0·0001 ) . More patients had good 3-month neurological outcome with Solitaire than with Merci ( 58%vs 33 % ; difference 25 % [ 6 - 43 ] , OR 2·78 [ 1·25 - 6·22 ] ; p(non-inferiority)=0·0001 , p(superiority)=0·02 ) . 90-day mortality was lower in the Solitaire group than it was in the Merci group ( 17 vs 38 ; difference -21 % [ -39 to -3 ] , OR 0·34 [ 0·14 - 0·81 ] ; p(non-inferiority)=0·0001 , p(superiority)=0·02 ) . INTERPRETATION The Solitaire Flow Restoration Device achieved substantially better angiographic , safety , and clinical outcomes than did the Merci Retrieval System . The Solitaire device might be a future treatment of choice for endovascular recanalisation in acute ischaemic stroke . FUNDING Covidien/ev3 R and omized clinical trials are design ed with stopping boundaries to guide data monitoring committees with their decision making concerning ongoing trials . In particular , when extremely positive results are seen and a boundary is crossed , the data monitoring committee may recommend releasing the results earlier to the public than at the definitive final analysis time specified in the protocol . For trials that are still accruing , this also means stopping accrual . Because the information about treatment efficacy is more limited in an early analysis than in a final analysis , questions have been raised about the appropriateness of incorporating early stopping for positive results in trial design s. In particular , there are concerns that treatment effects seen early may not be real or may be overly optimistic . To examine this issue , we collected information about treatment efficacy on National Cancer Institute Cooperative Group trials that were stopped early for positive results ( information both at the time the trial was stopped/released and at times of further follow-up ) . Twenty-seven such trials were located . For 17 of 18 of these trials with sufficient follow-up information , the treatment effect was similar or only slightly smaller at last follow-up compared with the stopping/release time . We critically evaluate reasons why one might be concerned about early stopping for positive results . We conclude that for trials with well- design ed interim monitoring plans , the ability to stop early for positive results is an important component of the trial design , allowing the public to benefit as soon as possible from the study conclusions A novel design for intervention studies is presented , the so called PROBE study ( Prospect i ve R and omized Open , Blinded End-point ) . This design is compared to the classical double-blind design . Among the advantages of the PROBE design are lower cost and greater similarity to st and ard clinical practice , which should make the results more easily applicable in routine medical care . Since end-points are evaluated by a blinded end-point committee it is obvious that there should be no difference between the two types of trials in this regard REVASCAT is a prospect i ve , multicenter , r and omized trial seeking to establish whether subjects meeting following main inclusion criteria : age 18–80 , baseline National Institutes of Health Stroke Scale ≥6 , evidence of intracranial internal carotid artery or proximal ( M1 segment ) middle cerebral artery occlusion , Alberta Stroke Program Early Computed Tomography score of > 7 on non-contrast CT or > 6 on diffusion-weighted magnetic resonance imaging , ineligible for or with persistent occlusion after intravenous alteplase and procedure start within 8 hours from symptom onset , have higher rates of favorable outcome when treated with the SolitaireTM FR embolectomy device compared to st and ard medical therapy alone The primary end-point , based on intention-to-treat criteria is the distribution of modified Rankin Scale scores at 90 days . Projected sample size is 690 patients . Estimated common odds ratio is 1•615 . R and omization is performed under a minimization process using age , baseline NIHSS , therapeutic window , occlusion location and investigational center . The study follows a sequential analysis ( triangular model ) with the first approach to test efficacy at 174 patients and subsequent analyses ( if necessary ) at 346 , 518 , and 690 subjects . Secondary end-points are infa rct volume evaluated on CT at 24 h , dramatic early favorable response , defined as NIHSS of 0–2 or NIHSS improvement ≥8 points at 24 h and successful recanalization in the Solitaire arm according to the thrombolysis in cerebral infa rct ion ( TICI ) classification defined as TICI 2b or 3 . Safety variables are mortality at 90 days , symptomatic intracranial haemorrhage rates at 24 hours and procedure related complications Rationale The Interventional Management of Stroke ( IMS ) I and II pilot trials demonstrated that the combined intravenous ( i.v . ) and intraarterial ( i.a . ) approach to recanalization may be more effective than st and ard i.v . rt-PA ( Activase ® ) alone for moderate-to-large National Institutes of Health Stroke Scale ( NIHSS ≥ 10 ) strokes , and with a similar safety profile . Aims The primary objective of this NIH-funded , Phase III , r and omized , multicenter , open-label clinical trial is to determine whether a combined i.v./i.a . approach to recanalization is superior to st and ard i.v . rt-PA alone when initiated within 3 h of acute ischemic stroke onset . The IMS III trial will develop and maintain a network of interventional centers to test the safety , feasibility , and potential efficacy of new FDA -approved catheter devices as part of a combined i.v./i.a . approach to recanalization as the IMS III study progresses . A secondary objective of the IMS III trial is to determine the cost-effectiveness of the combined i.v./i.a . approach as compared with st and ard i.v . rt-PA . Trial enrollment began in July of 2006 . Design A projected 900 subjects with moderate-to-large ( NIHSS ≥ 10 ) ischemic strokes between ages 18 and 80 will be enrolled over the next 5 years at 40-plus centers in the United States and Canada . Patients must have i.v . treatment initiated within 3 h of stroke onset in both arms . Subjects will be r and omized in a 2 : 1 ratio with more subjects enrolled in the combined i.v./i.a . group . The i.v . rt-PA alone group will receive the st and ard full dose [ 0·9 mg/kg , 90 mg maximum ( 10 % as bolus ) ] of rt-PA intravenously over an hour . The combined i.v./i.a . group will receive a lower dose of i.v . rt-PA ( ~0·6 mg/kg , 60 mg maximum ) over 40 min , followed by immediate angiography . If a treatable thrombus is not demonstrated , no i.a . therapy will be administered . If an appropriate thrombus is identified , treatment will continue with either the Concentric Merci ® thrombus-removal device , infusion of rt-PA and delivery of low-intensity ultrasound at the site of the occlusion via the EKOS ® Micro-Infusion Catheter , or infusion of rt-PA via a st and ard microcatheter . If i.a . rt-Pa therapy is the chosen strategy , a maximum of 22 mg of i.a . rt-PA may be given . The choice of i.a . strategy will be made by the treating neurointerventionalist . The i.a . treatment must begin within 5 h and be completed within 7 h of stroke onset . Study outcomes The primary outcome measure is a favorable clinical outcome , defined as a modified Rankin Scale Score of 0–2 at 3 months . The primary safety measure is mortality at 3 months and symptomatic ICH within the 24 h of r and omization BACKGROUND Endovascular therapy is increasingly used after the administration of intravenous tissue plasminogen activator ( t-PA ) for patients with moderate-to-severe acute ischemic stroke , but whether a combined approach is more effective than intravenous t-PA alone is uncertain . METHODS We r and omly assigned eligible patients who had received intravenous t-PA within 3 hours after symptom onset to receive additional endovascular therapy or intravenous t-PA alone , in a 2:1 ratio . The primary outcome measure was a modified Rankin scale score of 2 or less ( indicating functional independence ) at 90 days ( scores range from 0 to 6 , with higher scores indicating greater disability ) . RESULTS The study was stopped early because of futility after 656 participants had undergone r and omization ( 434 patients to endovascular therapy and 222 to intravenous t-PA alone ) . The proportion of participants with a modified Rankin score of 2 or less at 90 days did not differ significantly according to treatment ( 40.8 % with endovascular therapy and 38.7 % with intravenous t-PA ; absolute adjusted difference , 1.5 percentage points ; 95 % confidence interval [ CI ] , -6.1 to 9.1 , with adjustment for the National Institutes of Health Stroke Scale [ NIHSS ] score [ 8 - 19 , indicating moderately severe stroke , or ≥20 , indicating severe stroke ] ) , nor were there significant differences for the predefined subgroups of patients with an NIHSS score of 20 or higher ( 6.8 percentage points ; 95 % CI , -4.4 to 18.1 ) and those with a score of 19 or lower ( -1.0 percentage point ; 95 % CI , -10.8 to 8.8 ) . Findings in the endovascular-therapy and intravenous t-PA groups were similar for mortality at 90 days ( 19.1 % and 21.6 % , respectively ; P=0.52 ) and the proportion of patients with symptomatic intracerebral hemorrhage within 30 hours after initiation of t-PA ( 6.2 % and 5.9 % , respectively ; P=0.83 ) . CONCLUSIONS The trial showed similar safety outcomes and no significant difference in functional independence with endovascular therapy after intravenous t-PA , as compared with intravenous t-PA alone . ( Funded by the National Institutes of Health and others ; Clinical Trials.gov number , NCT00359424 . ) Background and Hypothesis Thrombolysis with tissue plasminogen activator is proven to reduce disability when given within 4.5 h of ischemic stroke onset . However , tissue plasminogen activator only succeeds in recanalizing large vessel arterial occlusion in a minority of patients . We hypothesized that anterior circulation ischemic stroke patients , selected with ‘ dual target ’ vessel occlusion and evidence of salvageable brain using computed tomography or magnetic resonance imaging ‘ mismatch ’ within 4.5 h of onset , would have improved reperfusion and early neurological improvement when treated with intra-arterial clot retrieval after intravenous tissue plasminogen activator compared with intravenous tissue plasminogen activator alone . Study Design EXTEND-IA is an investigator-initiated , phase II , multicenter prospect i ve , r and omized , open-label , blinded-endpoint study . Ischemic stroke patients receiving st and ard 0.9 mg/kg intravenous tissue plasminogen activator within 4.5 h of stroke onset who have good prestroke functional status ( modified Rankin Scale < 2 , no upper age limit ) will undergo multimodal computed tomography or magnetic resonance imaging . Patients who also meet dual target imaging criteria : vessel occlusion ( internal carotid or middle cerebral artery ) and mismatch ( perfusion lesion : ischemic core mismatch ratio > 1.2 , absolute mismatch > 10 ml , ischemic core volume < 70 ml ) will be r and omized to either clot retrieval with the Solitaire FR device after full dose intravenous tissue plasminogen activator , or tissue plasminogen activator alone . Study Outcomes The co primary outcome measure will be reperfusion at 24 h and favorable clinical response ( reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0–1 ) at day 3 . Secondary outcomes include modified Rankin Scale at day 90 , death , and symptomatic intracranial hemorrhage BACKGROUND The IMS III trial did not show a clinical benefit of endovascular treatment compared with intravenous alteplase ( recombinant tissue plasminogen activator ) alone for moderate or severe ischaemic strokes . Late reperfusion of tissue that was no longer salvageable could be one explanation , as suggested by previous exploratory studies that showed an association between time to reperfusion and good clinical outcome . We sought to vali date this association in a preplanned analysis of data from the IMS III trial . METHODS We used data for patients with complete proximal arterial occlusions in the anterior circulation who received endovascular treatment and achieved angiographic reperfusion ( score on Thrombolysis in Cerebral Infa rct ion scale of grade 2 - 3 ) during the endovascular procedure ( within 7 h of symptom onset ) . We used logistic regression to model good clinical outcome ( defined as a modified Rankin Scale score of 0 - 2 at 3 months ) as a function of the time to reperfusion . We prespecified variables to be considered for adjustment , including age , baseline National Institutes of Health Stroke Scale score , sex , and baseline blood glucose concentration . FINDINGS Of 240 patients who were otherwise eligible for inclusion in our analysis , 182 ( 76 % ) achieved angiographic reperfusion . Mean time from symptom onset to reperfusion ( ie , procedure end ) was 325 min ( SD 52 ) . Increased time to reperfusion was associated with a decreased likelihood of good clinical outcome ( unadjusted relative risk for every 30-min delay 0·85 [ 95 % CI 0·77 - 0·94 ] ; adjusted relative risk 0·88 [ 0·80 - 0·98 ] ) . INTERPRETATION Delays in time to angiographic reperfusion lead to a decreased likelihood of good clinical outcome in patients after moderate to severe stroke . Rapid reperfusion could be crucial for the success of future acute endovascular trials . FUNDING US National Institutes of Health and National Institute of Neurological Disorders and Stroke Background — Meaningful delays occurred in the Interventional Management of Stroke ( IMS ) III trial . Analysis of the work flow will identify factors contributing to the in-hospital delays . Methods and Results — In the endovascular arm of the IMS III trial , the following time intervals were calculated : stroke onset to emergency department arrival ; emergency department to computed tomography ( CT ) ; CT to intravenous tissue plasminogen activator start ; intravenous tissue plasminogen activator start to r and omization ; r and omization to groin puncture ; groin puncture to thrombus identification ; thrombus identification to start of endovascular therapy ; and start of endovascular therapy to reperfusion . The effects of enrollment time , CT angiography use , interhospital transfers , and intubation on work flow were evaluated . Delays occurred notably in the time intervals from intravenous tissue plasminogen activator initiation to groin puncture ( median 84 minutes ) and start of endovascular therapy to reperfusion ( median 85 minutes ) . The CT to groin puncture time was significantly shorter during working hours than after . Times from emergency department to reperfusion and groin puncture to reperfusion decreased over the trial period . Patients with CT angiography had shorter emergency department to reperfusion and onset to reperfusion times . Transfer of patients result ed in a longer onset to reperfusion time compared with those treated in the same center . Age , sex , National Institutes of Health Stroke Scale score , and intubation did not affect delays . Conclusions — Important delays were identified before reperfusion in the IMS III trial . Delays decreased as the trial progressed . Use of CT angiography and endovascular treatment in the same center were associated with time savings . These data may help in optimizing work flow in current and future endovascular trials . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00359424 |
12,170 | 25,773,054 | Individual analyses of these studies did not show significant differences between the leukotriene inhibitors group and the control group in symptom-free days and incidence of recurrent wheezing .
The current evidence does not allow definitive conclusions to be made about the effects of leukotriene inhibitors on length of hospital stay and clinical severity score in infants and young children with bronchiolitis . | BACKGROUND Bronchiolitis is an acute inflammatory illness of the bronchioles common among infants and young children .
It is often caused by the respiratory syncytial virus ( RSV ) .
Management of bronchiolitis varies between clinicians , reflecting the lack of evidence for a specific treatment approach .
The leukotriene pathway has been reported to be involved in the pathogenesis of bronchiolitis .
Leukotriene inhibitors such as montelukast have been used in infants and young children with bronchiolitis .
However , the results from limited r and omised controlled trials ( RCTs ) are controversial and necessitate a thorough evaluation of their efficacy for bronchiolitis in infants and young children .
OBJECTIVES To assess the efficacy and safety of leukotriene inhibitors for bronchiolitis in infants and young children . | Summary Background Leukotriene B4 ( LTB4 ) recruits and activates neutrophils . Accordingly , this leukotriene is involved in innate defense actions . Objective To examine if nasal LTB4 can produce neutrophil activity and to explore whether or not LTB4 can condition neutrophils to exert virucidal effects in vitro and in vivo . Methods 1 . Twenty-three healthy subjects received nasal LTB4 in a r and omized and sham-controlled design . Symptoms were scored and nasal lavages carried out . Myeloperoxidase ( MPO ) and α-defensins were monitored as indices of neutrophil activity . IL-8 , eosinophil cationic protein ( ECP ) and α2-macroglobulin were measured as indices of pro-inflammatory cytokine production , eosinophil activity , and plasma exudation . 2 . Supernatants from neutrophils activated by LTB4 in vitro were assayed for virucidal activity against respiratory viruses . 3 . In 38 healthy individuals , nasal inoculation with human rhinovirus-16 ( HRV-16 ) was performed . In a preliminary study , intervention with LTB4 was given in a r and omized and controlled design . Symptoms , virus replication , and antibody-titres were monitored . Results 1 . LTB4 produced statistically significant increases in MPO and α-defensins , whereas IL-8 , ECP , and α2-macroglobulin were unaffected . 2 . The supernatants efficiently killed human coronavirus , respiratory syncytial virus , and influenza B virus . 3 . HRV-16 replication was lower in subjects receiving LTB4 , but this difference failed to reach statistical significance . Common cold symptoms and incidence of seroconversion were unaffected . Conclusion Nasal LTB4 induces a selective recruitment/activation of neutrophils . LTB4 can condition neutrophils to exert virucidal effects in vitro and may reduce virus replication in vivo . We suggest that the condition induced by LTB4 reflects an enhanced state of innate defense BACKGROUND . Cysteinyl leukotrienes are implicated in the inflammation of bronchiolitis . Recently , a specific cysteinyl leukotriene receptor antagonist , montelukast ( Singulair [ MSD , Haarlem , Netherl and s ] ) , has been approved for infants in granule sachets . OBJECTIVE . Our goal was to evaluate the effect of montelukast on clinical progress and on cytokines in acute bronchiolitis . METHODS . This was a r and omized , placebo-controlled , double-blind , parallel-group study in 2 medical centers . Fifty-three infants ( mean age : 3.8 ± 3.5 months ) with a first episode of acute bronchiolitis were r and omly assigned to receive either 4-mg montelukast sachets or placebo , every day , from hospital admission until discharge . The primary outcome was length of stay , and secondary outcomes included clinical severity score ( maximum of 12 ) and changes in type 1 and 2 cytokine levels ( including interleukin4/IFN-γ ratio as a surrogate for the T-helper 2/T-helper 1 ratio ) in nasal lavage . RESULTS . Both groups were comparable at baseline , and cytokine levels correlated positively with disease severity . There were neither differences in length of stay ( 4.63 ± 1.88 [ placebo group ] vs 4.65 ± 1.97 days [ montelukast group ] ) nor in clinical severity score and cytokine levels between the 2 groups . No differences in interleukin 4/IFN-γ ratio between the 2 groups were seen . There was a slight tendency for infants in the montelukast group to recover more slowly than those in the placebo group ( clinical severity score at discharge : 6.1 ± 2.4 vs 4.8 ± 2.2 , respectively ) . CONCLUSIONS . Montelukast did not improve the clinical course in acute bronchiolitis . No significant effect of montelukast on the T-helper 2/T-helper 1 cytokine ratio when given in the early acute phase could be demonstrated Background : Controlled clinical trials on the effects of leukotriene antagonists on asthma‐like symptoms , bronchial hyperresponsiveness and airway inflammation have not been performed in elite athletes Effective treatment of respiratory symptoms , airway inflammation and impairment of lung function is the goal of any asthma therapy . Although montelukast has been shown to be a possible add-on therapy for anti-inflammatory treatment in older children , its efficacy in infants and young children is not well known . The aim of this study was to investigate its effect in infants and young children with early childhood asthma . In a prospect i ve r and omised double-blind placebo-controlled study , 24 young children ( 10–26 months ) with wheeze , allergy and a positive family history of asthma consistent with the diagnosis of early childhood asthma were r and omised to receive montelukast 4 mg or placebo . The forced expiratory volume in 0.5 seconds ( FEV0.5 ) was measured using the raised volume rapid thoracic compression technique , and fractional exhaled nitric oxide ( FeNO ) and symptom scores were determined . No change was noted in FEV0.5 , FeNO or symptom score in the placebo group following the treatment period . In contrast , significant improvements in mean±sd FEV0.5 ( 189.0±37.8 and 214.4±44.9 mL before and after treatment , respectively ) , FeNO ( 29.8±10.0 and 19.0±8.5 ppb ) and median symptom score ( 5.5 and 1.5 ) were noted following treatment with montelukast . In conclusion , montelukast has a positive effect on lung function , airway inflammation and symptom scores in very young children with early childhood asthma RATIONALE A pilot study ( Bisgaard H ; Study Group on Montelukast and Respiratory Syncytial Virus . A r and omized trial of montelukast in respiratory syncytial virus postbronchiolitis . Am J Respir Crit Care Med 2003;167:379 - 383 ) reported the efficacy of montelukast in post-respiratory syncytial virus ( RSV ) bronchiolitic respiratory symptoms . OBJECTIVES To evaluate the efficacy and safety of montelukast , 4 and 8 mg , in treating recurrent respiratory symptoms of post-RSV bronchiolitis in children in a large , multicenter study . METHODS This was a double-blind study of 3- to 24-month-old children who had been hospitalized for a first or second episode of physician-diagnosed RSV bronchiolitis and who tested positive for RSV . Patients ( n = 979 ) were r and omized to placebo or to montelukast at 4 or 8 mg/day for 4 weeks ( period I ) and 20 weeks ( period II ) . The primary end point was percentage symptom-free days ( % SFD ; day with no daytime cough , wheeze , and shortness of breath , and no nighttime cough ) . MEASUREMENTS AND MAIN RESULTS No significant differences were seen between montelukast and placebo in % SFD over period I : mean + /- SD for placebo and for montelukast at 4 and 8 mg were 37.0 + /- 30.7 , 38.6 + /- 30.4 , and 38.5 + /- 29.9 , respectively . Least-squares mean differences ( 95 % confidence interval ) between montelukast ( 4 mg ) and placebo and between montelukast ( 8 mg ) and placebo were 1.9 % ( -2.9 , 6.7 ) and 1.6 % ( -3.2 , 6.5 ) , respectively . Secondary end points were similar across treatments . Both doses were generally well tolerated . During the first two treatment weeks , average % SFD was approximately 29 % . In post hoc analyses of patients ( n = 523 ) with persistent symptoms ( % SFD < or = 30 % over Weeks 1 - 2 ) , differences in % SFD were seen between montelukast and placebo over Weeks 3 - 24 : difference were 5.7 ( 0.0 , 11.3 ) for montelukast ( 4 mg ) minus placebo and 5.9 ( 0.1 , 11.7 ) for montelukast ( 8 mg ) minus placebo . CONCLUSIONS In this study , montelukast did not improve respiratory symptoms of post-RSV bronchiolitis in children Our aim was to investigate the effectiveness of montelukast in recurrently wheezy infants . We r and omised 113 , 6–24-month-old children with recurrent wheezing to receive either placebo or montelukast daily for an 8-week period . The primary end-point was symptom-free days . The secondary aims were to evaluate the effect of montelukast on rescue medication , on lung function , airway responsiveness and exhaled nitric oxide fraction ( FeNO ) . Clinical response and FeNO were determined , the functional residual capacity ( FRC ) and specific airway conductance ( sGaw ) were measured using an infant whole-body plethysmograph , the maximal flow at functional residual capacity ( V′max , FRC ) was recorded using the squeeze technique and airway responsiveness was evaluated by performing a dosimetric methacholine challenge test . There was no significant difference in changes in weekly symptom-free days between the montelukast and the placebo group ( 3.1–3.7 days versus 2.7–3.1 days , p = 0.965 ) . No significant differences were detected in the secondary end-points , i.e. use of rescue medication , FRC , sGaw , V′max , FRC , FeNO or airway responsiveness between groups . Montelukast therapy did not influence the number of symptom-free days , use of rescue medication , lung function , airway responsiveness or airway inflammation in recurrently wheezy , very young children BACKGROUND Acute wheezing illnesses in preschoolers require better management strategies to reduce morbidity . OBJECTIVES We sought to examine the effectiveness of episodic use of an inhaled corticosteroid and a leukotriene receptor antagonist in preschoolers with intermittent wheezing . METHODS In a r and omized , double-blind , placebo-controlled 12-month trial , 238 children aged 12 to 59 months with moderate-to-severe intermittent wheezing received 7 days of either budesonide inhalation suspension ( 1 mg twice daily ) , montelukast ( 4 mg daily ) , or placebo in addition to albuterol with each identified respiratory tract illness ( RTI ) . Proportion of episode-free days ( EFDs ) during the 12-month trial was the primary outcome . RESULTS The 3 treatment groups did not differ in proportions of EFDs , with adjusted mean EFDs of 76 % ( 95 % CI , 70 % to 81 % ) for budesonide , 73 % ( 95 % CI , 66 % to 79 % ) for montelukast , and 74 % ( 95 % CI , 65 % to 81 % ) for conventional therapy ( P = .66 ) . The 3 groups did not differ in oral corticosteroid use , health care use , quality of life , or linear growth . However , during RTIs , budesonide and montelukast therapy led to modest reductions in trouble breathing ( 38 % [ P = .003 ] and 37 % [ P = .003 ] , respectively ) and interference with activity scores ( 32 % [ P = .01 ] and 40 % [ P = .001 ] , respectively ) that were most evident in those with positive asthma predictive indices . CONCLUSIONS In preschool children with moderate-to-severe intermittent wheezing , episodic use of either budesonide or montelukast early in RTIs , when added to albuterol , did not increase the proportion of EFDs or decrease oral corticosteroid use over a 12-month period . However , indicators of severity of acute illnesses were reduced , particularly in children with positive asthma predictive indices BACKGROUND : Infections with viruses causing upper respiratory tract infection ( URI ) are associated with increased leukotriene levels in the upper airways . Montelukast , a selective leukotriene-receptor antagonist , is an effective treatment of asthma and allergic rhinitis . OBJECTIVE : To determine whether prophylactic treatment with montelukast reduces the incidence and severity of URI in children . METHODS : A r and omized , double-blind , placebo-controlled study was performed in 3 primary care pediatric ambulatory clinics in Israel . Healthy children aged 1 to 5 years were r and omly assigned in a 1:1 ratio to receive 12-week treatment with 4 mg oral montelukast or look-alike placebo . Patients were excluded if they had a previous history of reactive airway disease . A study coordinator contacted the parents by phone once a week to obtain information regarding the occurrence of acute respiratory episodes . The parents received a diary card to record any acute symptoms of URI . The primary outcome measure was the number of URI episodes . RESULTS : Three hundred children were recruited and r and omly assigned into montelukast ( n = 153 ) or placebo ( n = 147 ) groups . One hundred thirty-one ( 85.6 % ) of the children treated with montelukast and 129 ( 87.7 % ) of the children treated with placebo completed 12 weeks of treatment . The number of weeks in which URI was reported was 30.4 % in children treated with montelukast and 30.7 % in children treated with placebo . There was no significant difference in any of the secondary variables between the groups . CONCLUSIONS : In preschool-aged children , 12-week treatment with montelukast , compared with placebo , did not reduce the incidence of URI Infants often develop reactive airway disease after respiratory syncytial virus ( RSV ) bronchiolitis . Cysteinyl-leukotrienes ( cys-LT ) are released during RSV infection and may contribute to the inflammation . We hypothesized that a cys-LT receptor antagonist would ameliorate reactive airway disease subsequent to RSV bronchiolitis . One hundred and thirty infants who were 3 to 36 months old , hospitalized with acute RSV bronchiolitis , were r and omized into a double-blind , parallel comparison of 5-mg montelukast chewable tablets or matching placebo given for 28 days starting within 7 days of symptom debut . Infants with a suspected history of asthma were excluded . One hundred sixteen infants provided diary card data for the treatment period . Median age was 9 months . Infants on montelukast were free of any symptoms on 22 % of the days and nights compared with 4 % of the days and nights in infants on placebo ( p = 0.015 ) . Daytime cough was significantly reduced on active treatment ( p = 0.04 ) . Exacerbations were significantly delayed from montelukast compared with placebo ( p < 0.05 ) . In conclusion , cys-LT antagonist treatment reduces lung symptoms subsequent to RSV bronchiolitis Asthma is a common and chronic inflammatory condition of the airways whose cause is not completely understood . Although many classes of drugs are used for management of asthma , the response is variable due to multifactor reasons . This study was design ed to evaluate the outcome of using ketotifen or montelukast sodium in Iraqi asthmatic patients . Single blinded r and omized clinical trial was utilized , in which 100 asthmatic patients were recruited from Al-Karama hospital and r and omized into two groups ; 1st group ( 50 patients , treated with ketotifen for 4 weeks ) and 2nd group ( 50 patients treated with montelukast sodium for 4 weeks ) . Asthma symptom score and wheezing were recorded at the beginning ( first visit ) and at the end of the study ( after one month ) . Pulmonary function tests ( PFTs ) were performed by spirometry , and the patients ' use of asthma drugs and their symptoms were evaluated at each visit . The result showed that asthma symptom , chest wheezing , and PFT values were significantly improved in the two groups at the end of the study compared to first visit ( p < 0.05 ) . All symptoms were significantly lower and PFT values were higher in the 2nd group compared to 1st group ( p < 0.05 ) . In conclusion , both ketotifen and montelukast sodium showed significant changes in asthma symptoms and PFT after one month of treatment , but the changes were more significant with montelukast group ( 2nd group ) compared with ketotifen group ( 1st group ) and this indicate that montelukast was more effective than ketotifen in treatment of asthmatic patients OBJECTIVE To investigate the effect of montelukast on eosinophil degranulation and recurrent wheezing episodes in post-respiratory syncytial virus ( RSV ) bronchiolitis . STUDY DESIGN Two hundred infants ( age , 6 - 24 months ) who were hospitalized with their first episode of acute RSV bronchiolitis were r and omized in a double-blind , placebo-controlled , parallel comparison of 4-mg montelukast granules ( RSV-MONT group ) or matching placebo ( RSV-PLC group ) administered for 3 months . Serum eosinophil-derived neurotoxin ( EDN ) levels were measured ( primary outcome ) , and recurrent wheezing was documented ( secondary outcome ) for 12 months . Comparisons were made with control subjects ( control group , n = 50 ) . RESULTS At the end of the 3-month treatment period , the RSV-PLC group ( n = 71 ) exhibited significantly elevated EDN levels ( P < .0001 ) , and the RSV-MONT group ( n = 79 ) showed significantly decreased EDN levels ( P < .01 ) when compared with the initial levels . As a result , EDN levels in the 2 RSV groups significantly differed at this point ( P < .0001 ) and remained different for the entire 12-month follow-up period . Cumulative recurrent wheezing episodes at 12 months were significantly lower in the RSV-MONT group ( P = .039 ) . CONCLUSION Montelukast treatment reduces eosinophil degranulation and is associated with a decrease in recurrent wheezing episodes in post-RSV bronchiolitis Acute respiratory syncytial virus (RSV)-induced bronchiolitis is often associated with continuing respiratory symptoms following hospitalization . To date , there is no vali date d objective measure to evaluate symptoms of RSV-induced bronchiolitis . We report on the reliability , validity , and responsiveness of the bronchiolitis caregiver diary ( BCD ) of symptoms and healthcare utilization associated with postacute RSV . The BCD measures four symptoms ( daytime cough , wheeze , trouble breathing , and nighttime cough ) , healthcare utilization , and rescue medication for worsening of lung symptoms . Data from the 4-week treatment period of the reported prospect i ve , placebo-controlled trial of montelukast for treatment of postacute RSV were used to assess reliability ( internal consistency and test-retest ) , construct validity ( cross-sectional and longitudinal correlations ) , discriminant validity ( known-groups analyses ) , and responsiveness . The primary outcome of this study was the percentage of symptom-free days ( SFD ) . The secondary outcome was a composite symptom score ( CSS ; average of daytime cough , wheezing , and trouble breathing ) . Cronbach 's alpha of 0.85 indicated that the four symptoms were internally consistent , supporting a unidimensional scale structure . Test-retest reliabilities for the percentage of SFD and CSS were above the recommended cut point of 0.70 . Cross-sectional and longitudinal correlations were sizeable and statistically significant , demonstrating construct validity . Hypothesized known-group differences were statistically significant in the appropriate direction . Responsiveness analyses indicated moderate effect sizes for percentage of SFD . In conclusion , the BCD provides a valid , reliable , and responsive tool for the assessment of symptoms of postacute RSV-induced bronchiolitis , capable of measuring moderate effect sizes , and demonstrating responsiveness to therapy RATIONALE Beneficial effects of anti-inflammatory therapy such as fluticasone propionate ( FP ) and montelukast ( Mk ) have been demonstrated in preschool children with asthma . However , comparative studies are lacking in this age group . Therefore , we conducted a study to evaluate and compare the effect of FP and Mk in preschool children with asthma-like symptoms . METHODS In this multicenter , r and omized , placebo-controlled , double-blind , double-dummy trial , children aged 2 - 6 years with asthma-like symptoms were included . In total , 63 children were r and omly allocated to receive FP ( 25 ) , Mk ( 18 ) or placebo ( 20 ) for 3 months . The primary outcome was the daily symptom score ( wheeze , cough , shortness of breath ) as recorded by caregivers in a symptom diary card . Secondary endpoints were rescue medication free days , blood eosinophils and lung function ( interrupter technique and forced oscillation technique ( FOT ) ) . RESULTS During the 3 months study period , symptoms improved in all 3 groups , with a statistically significant difference between FP and placebo in favor of the FP group ( p=0.021 ) . A significant reduction in circulating eosinophils after 3 months of treatment was found in the Mk group only ( p=0.008 ) , which was significantly different from the change found in the placebo group ( p=0.045 ) . With the exception of frequency dependence ( measured by FOT ) , which showed a difference between FP and Mk after 3 months of treatment in favor of the FP group ( p=0.048 ) , no differences in lung function within or between groups were found . CONCLUSIONS In spite of a lack of power , our results suggest that FP has a beneficial effect on symptoms and Mk on blood eosinophil level as compared to placebo . Except for a difference in one lung function parameter after 3 months between FP and Mk in favor of the FP group , this study revealed no differences between FP and Mk BACKGROUND AND OBJECTIVE Exercise-induced wheeze ( EIW ) is common . Several treatment options exist . Patients with low fraction of exhaled nitric oxide ( F(E)NO ) are unlikely to be steroid-responsive and might benefit from non-steroidal therapies . We assessed : the efficacy of cromoglycate , formoterol and montelukast in patients with EIW and low F(E)NO ( < 35 ppb ) in a r and omized cross-over trial , and the efficacy of inhaled corticosteroid in a high F(E)NO ( > 35 ppb ) group . METHODS Patients had EIW and airway hyperresponsiveness ( AHR ) to mannitol and /or exercise . Those with low F(E)NO ( n = 19 ) received cromoglycate ( 20 mg inh . bd + before challenge tests ) , formoterol ( 12 microg inh . bd + before challenge tests ) and montelukast ( 10 mg p.o . od ) , each for 2 weeks . Those with high F(E)NO ( n = 20 ) took inhaled fluticasone ( 500 microg ) daily for 4 weeks . Primary end-points were : 50 % reduction in maximum FEV(1 ) % fall ( clinical protection ) and decrease in AHR to mannitol . RESULTS In patients with low F(E)NO , cromoglycate , formoterol and montelukast significantly decreased AHR to mannitol in 63 % , 61 % and 47 % of patients , respectively . In this group , the magnitude of exercise-induced bronchoconstriction ( EIB ) was significantly reduced with montelukast and formoterol ; between-treatment differences were not significant . Of 6/19 with low F(E)NO and EIB , protection occurred in 67 % ( cromoglycate ) , 83 % ( formoterol ) and 50 % ( montelukast ) , respectively . In the high F(E)NO group , AHR to mannitol and EIB decreased significantly with fluticasone ( P < 0.001 , P = 0.005 , respectively ) , and protection occurred in 7/8 ( 88 % ) with EIB . CONCLUSIONS In patients with EIW and low F(E)NO , the number of ' responders ' to cromoglycate , formoterol and montelukast was similar . In a high F(E)NO population the response to inhaled corticosteroid was highly significant and comparable to previous studies This study was design ed to evaluate the effect of once-daily montelukast therapy on the clinical progress and the cytokine profile of patients with acute viral bronchiolitis . A r and omized , double-blind , placebo-controlled trial included 85 patients ( mean age , 3.5 + /- 2.35 months ) , clinical ly diagnosed as first-episode acute bronchiolitis in addition to 10 healthy controls of matched age and sex . Patients were r and omly assigned to receive either montelukast ( 4-mg sachets ; n = 47 ) or placebo ( n = 38 ) daily from the time of admission until discharge . The primary outcome measure was the length of hospital stay ( LOS ) , and clinical severity scores ( CSs ) and changes in plasma levels of interferon gamma and interleukin-4 were secondary outcomes . LOS for the montelukast group was found to be significantly lower than that of the placebo group ( p < 0.05 ) . This effect was also found at nonsignificant levels among patients with a positive family history of asthma or allergy . Moreover , cases receiving montelukast showed lower CSs all through the hospital stay that were significant in the first 24 hours ( p < 0.05 ) . Montelukast is probably of benefit as an episodic modifier in infants with acute viral bronchiolitis AIM The simplification of the management of asthma in the different clinical phases of this common chronic inflammatory disorder is the main goal of therapy . Pycnogenol ® , a st and ardized extract of French maritime pine bark , inhibits expression of 5-lipoxygenase and consequently decreases leukotriene levels in asthmatic patients . Pycnogenol ® anti-inflammatory activities may be supportive when taken in addition to inhalation corticosteroid ( ICS ) , putatively allowing for a reduction in dosage and frequency of ICS administration . METHODS This study evaluated the efficacy of Pycnogenol ® during a period of six months for improving allergic ( mite in house dust ) asthma management in patients with stable , controlled conditions . Pycnogenol ® was used at a daily dosage of 100 mg , distributed as 50 mg in the morning at 9 am and again in the evening at 9 pm ) . An individual patient 's asthma condition was grade d in five steps based on the daily dosage of inhaled fluticasone propionate with step 1 indicating 0 µg and step 5 the maximum dose of 500 µg ICS twice daily . RESULTS A total 76 patients were enrolled for this study . The group taking Pycnogenol ® in addition to ICS and the group taking only ICS were comparable for age , gender and clinical characteristics including FEV1 . The analysis of therapeutic ranking steps showed that 55 % of patients taking Pycnogenol ® improved as judged by passing to a lower ICS dose step . In comparison , only 6 % of patients depending exclusively on ICS progressed to a lower ( ICS dose ) therapeutic step . No deterioration ( passage to a higher ICS therapeutic step ) was observed in the Pycnogenol ® group , whereas in 18.8 % of patients depending exclusively on corticosteroids a deterioration requiring a higher dosage step was observed . The passage to different therapeutic steps was statistical significant between groups ( P<0.05 ) . Drop-outs were associated entirely to irregularities in follow-up and not due to medical reasons . No serious adverse events were observed in both groups and tolerability of Pycnogenol ® was very good . The levels of asthma control in the 6 interventional months as compared to the same period in the previous year were compared . In the Pycnogenol ® group , night-awakenings were less frequent , the number of days with PEF<80 % were decreased , days with asthma score > 1 were lower , requirement for salbutamol and additional asthma medication less frequent , and consultation of general practitioner and specialist required less commonly . All these parameters were statistical significantly improved in Pycnogenol ® + ICS group versus the ICS control group where no considerable changes were observed . Various common signs and symptoms were evaluated by visual analog scale , ( dry ) cough , severity of chest symptoms , wheezing , dyspnea and daytime symptoms . In the ICS-only group values did not improve while they did improve significantly in the ICS + Pycnogenol ® group ( P<0.05 vs. ICS only group ) . A decrease by 15.2 % of the specific IgE titer was found in the Pycnogenol ® + ICS group , whereas the titer increased by 13.4 % in the ICS-only group , while IgG1 and IgG4 remained unchanged in both groups . CONCLUSION Pycnogenol ® administration was effective for better control of signs and symptoms of allergic asthma and reduced the need for medication |
12,171 | 19,299,793 | The paramedian as opposed to midline needle approach and smaller epidural needle or catheter gauges do not reduce the risk of epidural vein cannulation .
CONCLUSION : The risk of intravascular placement of a lumbar epidural catheter in pregnancy may be reduced with the lateral patient position , fluid predistension , a single orifice catheter , a wire-embedded polyurethane epidural catheter and limiting the depth of catheter insertion to 6 cm or less . | BACKGROUND : In this systematic review , we evaluated the evidence for seven strategies which have been proposed to minimize the incidence of epidural vein cannulation during lumbar epidural catheter placement in pregnant women . | The position of lumbar epidural catheters was confirmed by radiography in 71 patients . Catheters were advanced by 5 cm cephalad in the lumbar epidural space by paramedian approach ( Group P : n = 28 ) or median one ( Group M : n = 43 ) and contrast media was injected through the catheters . If the contrast media was present in the paravertebral regions , the catheter was considered to be in the abnormal position . The incidence of the abnormal position of the catheters was higher in group M than in group P significantly . To advance an epidural catheter longer into the lumbar epidural space , paramedian approach may be superior to median one Epidural catheter insertion may be associated with blood vessel trauma or nerve root irritation . The purpose of this study was to assess whether the injection of small amounts of fluid through the Tuohy needle prior to catheter insertion reduced the incidence of these and other minor complications . Two hundred patients in labour , requesting epidural analgesia , were r and omly assigned to one of three groups : Group I —the catheter was inserted without previous injection of fluid ; Group II —3 ml , 1.5 per cent lidocaine hydrochloride was injected through the needle prior to catheter insertion ; Group III —3 ml , saline was injected prior to catheter insertion . There were no differences among the groups in the incidence of blood vessel trauma or paraesthesiae . We conclude that there is no advantage in injecting of fluid routinely into the epidural space prior to catheter insertion . RésuméUn cathéter qui pénètre dans l’espace épidural peut irriter une racine nerveuse ou transpercer un vaisseau . Nous avons essayé de diminuer l’incidence de ces complications en injectant du liquide dans l’aiguille de Tuohy avant d’y introduire le cathéter . Nous avons r and omisé en trois groupes , 200 c and i date s à l’analgésie épidurale pendant le travail . Dans le groupe I , nous insérions le cathéter sans injection préalable alors que dans les groupes II et III , nous injections respectivement 3 ml de lidocaïne à 1,5 pour cent et 3 ml de soluté physiologique avant de passer le cathéter . Nous n’avons pu démontrer quelque différence que ce soit entre les groupes quant à l’incidence de traumatisme vasculaire ou de paresthésie . Il ne semble donc pas y avoir d’avantage à injecter de liquide dans l’espace épidural avant d’y introduire un cathéter The extent of epidural anaesthesia and pattern of spread of contrast medium , using different injection techniques , has not been well documented . Therefore , in this prospect i ve , r and omized , double-blind study , the extent of anaesthesia and pattern of spread of contrast medium following an epidural bolus injection , via either a Tuohy needle or an epidural catheter , were compared . The study had two parts . In the first , 59 of 79 patients scheduled for a lower extremity operation under epidural anaesthesia were r and omly allocated to one of the two groups . Anaesthesia was achieved with an epidural injection of 10 to 15 ml ( including a 3 ml test dose ) of 0.75 % ropivacaine and fentanyl 25 μg via either a Tuohy needle ( Group N , n=31 ) or a catheter ( Group C , n=28 ) . The level of sensory anaesthesia was recorded . In the second part , the remaining 20 patients were r and omized to initially receive 5 ml of contrast medium via either a Tuohy needle ( Group NE , n=10 ) or a catheter ( Group CE , n=10 ) . The extent of spread was recorded radiologically . Unilateral or missed blocks and additional dose requirement were absent in Groups N and C. No differences were found in the extent of sensory anaesthesia or the spread of contrast medium . Twenty per cent of catheter tips lay outside the lateral margins of the vertebral bodies . We found that an epidural bolus injection , via either a Tuohy needle or a catheter , made no difference in regard to spread of local anaesthetic or contrast medium in the epidural space The effects of injecting normal saline 4 ml through the epidural needle before catheter passage on ease of catheterisation and incidence of certain complications were investigated in 189 non-obstetric patients . The use of saline had no effect on ease of catheterisation , with 84.2 % of Group S patients ( saline , n = 95 ) and 88.3 % of Group C patients ( control , n = 94 ) having the difficulty of passing the catheter rated as " easy " ( P = 0.31 ) . The incidence of complications was not affected by the use of saline . Paraesthesia occurred in 27.4 % of Group S patients compared with 16.0 % of Group C patients ( P = 0.08 ) . Epidural venous cannulation occurred in 6.3 % of Group S patients versus 11.7 % of Group C patients ( P = 0.30 ) . We conclude that the use of 5 ml of normal saline prior to catheter threading provides no significant benefit in improving the ease of catheterisation or decreasing the incidence of catheter complications A system has been constructed to evaluate the design , implementation , and analysis of r and omized control trials ( RCT ) . The degree of quadruple blinding ( the r and omization process , the physicians and patients as to therapy , and the physicians as to ongoing results ) is considered to be the most important aspect of any trial . The analytic techniques are scored with the same emphasis as is placed on the control of bias in the planning and implementation of the studies . Description of the patient and treatment material s and the measurement of various controls of quality have less weight . An index of quality of a RCT is proposed with its pros and cons . If published papers were to approximate these principles , there would be a marked improvement in the quality of r and omized control trials . Finally , a reasonable st and ard design and conduct of trials will facilitate the interpretation of those with conflicting results and help in making valid combinations of undersized trials Although epidural anaesthesia and analgesia are widely used in obstetrics , there are no large contemporary prospect i ve series detailing associated complications . Prospect i ve data was collected on all obstetric epidural blocks performed for labour and delivery in a single institution between July 1989 and August 1994 . A data entry sheet was compiled and entered onto a computer data base . Confidence intervals for proportions were calculated using st and ard methods . Information from 10 995 epidural blocks was analysed . Epidural analgesia in labour was the primary indication in 7648 , and anaesthesia for caesarean section in 3311 . Minor complications included failed or ab and oned insertion ( incidence 0.5 % ) , reinsertion of the epidural catheter ( 5 % ) , and inadequate anaesthesia ( 1.7 % ) or analgesia ( 0.9 % ) . Three percent were associated with venous puncture and 0.6 % with accidental dural puncture . Maternal mortality was zero . Unexpectedly high blocks occurred on eight occasions ( 0.07 % ) , two requiring intubation and ventilation . Three women ( 0.06 % ) experienced mild respiratory depression after postoperative epidural opioid . There was no major local anaesthetic toxicity or neurological deficit . The incidence of potentially life-threatening morbidity was thus 0.02 % although in both cases outcome was good . The only persisting complication was neurological , an apparent epidural catheter-induced traumatic mononeuropathy BACKGROUND The technique of epidural volume extension ( EVE ) involves the injection of saline into the extradural space immediately following the intrathecal injection , as part of a combined spinal-epidural ( CSE ) anaesthetic . One of the suggested benefits of EVE is a reduction in local anaesthetic required . The aim of this study was to test this hypothesis by comparing the median effective doses ( ED50 ) of hyperbaric bupivacaine with fentanyl 25 microg with and without EVE for Caesarean section . METHODS Sixty women were r and omized to receive either CSE anaesthesia with EVE ( EVE group ) or no EVE ( NEVE group ) . Using a double-blinded , up-down sequential technique , varying doses of bupivacaine with fentanyl 25 microg were administered . ED50 was estimated from up-down reversals and probit regression . RESULTS The ED50 for bupivacaine was similar and not significantly different in the two groups ( 5.1 mg in the EVE and 6.1 mg in the NEVE group ; difference 1.0 mg , 95 % CI -0.12 to 2.2 , P=0.08 ) . CONCLUSIONS This study illustrates that whilst low doses of intrathecal bupivacaine can be effectively used for Caesarean section , at such doses EVE does not appear to offer reliable or clinical ly relevant reductions in dosing with intrathecal bupivacaine Background This study prospect ively evaluated the ability of aspiration to detect intravascular placement of multiple‐orifice epidural catheters . Methods Multiple‐orifice , 20‐gauge epidural catheters were inserted in 1,029 laboring women . Catheters were observed and aspirated for blood or cerebrospinal fluid before they were tested with 2 ml local anesthetic . If the results of this test were negative ( no spinal anesthesia ) , the authors induced and maintained labor analgesia with a dilute local anesthetic and opioid solution . Patients with bilateral sensory change and effective labor analgesia had a “ positive ” epidural catheter . Women with unilateral block , inadequate analgesia despite some sensory change or those who delivered before being adequately assessed had “ equivocal ” catheters . Patients with neither analgesia nor sensory change had “ negative ” catheters . Results Aspiration and observation identified 60 intravenously placed catheters . Six catheters , which were placed initially in a blood vessel , were withdrawn until aspiration was negative , and then the anesthetic was infused . Four of these catheters were positive and two were still positioned intravascularly . Two other catheters may have been intravenously placed despite negative results of aspiration . The incidence of false‐negative results of aspiration was 0 to 2 of 1,085 ( upper limit of 95 % CI , 0.2 % to 0.4 % ) . No patient showed any signs or symptoms of local anesthetic toxicity . Conclusions Under the conditions of this study , which include using multiple‐orifice catheters and dilute solutions of local anesthetic and opioid , aspiration and incremental drug injection alone safeguard against the risks of intravenously positioned local anesthetics . These results should not be extrapolated to other clinical setting s without further study STUDY OBJECTIVE To compare a multiport , firm-tipped , close-ended , epidural catheter ( Portex catheter ) with a uniport , open-ended , soft-tipped , wire-reinforced catheter ( Arrow catheter ) in obstetric patients . STUDY DESIGN Prospect i ve data collection for intradepartmental quality assurance . SETTING Obstetric unit in a tertiary care maternity hospital . PATIENTS 2612 patients requesting labor analgesia . INTERVENTIONS The Arrow catheter was used in 1,352 women and the Portex catheter in 1,260 women . MEASUREMENTS AND MAIN RESULTS The incidence of unsatisfactory block were 3.3 % and 4.4 % with the Arrow and Portex catheters , respectively ( p = 0.2 ) . The catheter perforated the dura matter in 0.4 % of cases with both catheters . The incidence of epidural venipuncture was 1.1 % with the Arrow catheter and 5.7 % with the Portex catheter ( p = 0.0001 ) . Paresthesias occurred in 6 % of cases with the Arrow catheter and 11 . 2 % of cases with the Portex catheter ( p = 0.0001 ) . Epidural catheter reinsertion was required in fewer patients in the Arrow group than in the Portex group ( 4.8 % vs. 7.1 % ; p = 0.01 ) . CONCLUSIONS In obstetric patients , the softer uniport Arrow catheter produces paresthesias and venipunctures less frequently than the firm multiport Portex catheter Purpose To examine the effects of the volume of saline and the concentration of local anesthetic on the quality of anesthetic level . Methods One hundred and fifty two patients received thoracic epidural anesthesia were allocated into two groups ; mepivacaine 1 % ( 75 patients ) and 1.5 % ( 77 patients ) . Each group was r and omly divided into three sub-groups depending on epidural saline volumes of 1 ml , 5 ml , or 10 ml . Fifteen minutes after the injection of 10 ml mepivacaine , the dermatome levels of hypesthesia to cold and pinprick were determined by an individual blinded to the saline volume . Results The number of spinal segments with hypesthesia to cold in the three subgroups in the mepivacaine 1 % group were 12.5 [ 6–20 ] , 13 [ 8.5–20.5 ] and 12.5 [ 6.5–22 ] , respectively ( median [ range ] ) . The segments in the mepivacaine 1.5 % group were 12 [ 7–18.5 ] , 14 [ 8.5–19 ] * and 15 [ 6–23 ] * , respectively ( * P < 0.05vs 1 -ml group ) . The number of spinal segments with hypesthesia for pinprick in the three subgroups in the 1 % mepivacaine group were 10.5 [ 2–22 ] , 10.5 [ 4–17 ] and 11 [ 4–19 ] , respectively . The segments in the mepivacaine 1.5 % group were 12 [ 7.5–16 ] , 12 [ 7.5–17 ] and 11.5 [ 5–22.5 ] , respectively . Saline volume did not alter the anesthetic level of the mepivacaine 1 % , although it did affect the anesthetic spread of the mepivacaine 1.5 % . In both groups , a differential nerve block was elicited in the 5 ml and 10 ml saline subgroups . Conclusion When a large volume of saline is administered prior to local anesthetic , more differential blockade and a greater extent of anesthesia may be elicited . RésuméObjectifExaminer les effets du volume de solution salée et de la concentration d’anesthésique local sur la qualité de l’anesthésie . MéthodeCent cinquante-deux patients qui ont reçu une anesthésie péridurale thoracique ont été répartis en deux groupes : mépivacaïne 1 % ( 75 patients ) et 1,5 % ( 77 patients ) . Chaque groupe a été divisé au hasard en trois sous-groupes selon les volumes de solution salée péridurale administrée , 1 , 5 ou 10 ml . Quinze minutes après l’injection de 10 ml de mépivacaïne , le niveau du dermatome touché d’hypoesthésie au froid et à la piqûre a été déterminé par une personne ignorant le volume de solution salée donné . RésultatsLe nombre de segments médullaires atteints d’hypoesthésie au froid a été , dans les trois sous-groupes qui ont reçu la mépivacaïne 1 % , de 12,5 [ 6–20 ] , 13 [ 8,5–20,5 ] et de 12,5 [ 6,5–22 ] , respectivement ( médiane [ étendue ] ) . Dans le groupe qui a reçu la mépivacaïne 1,5 % , les segments ont été : 12 [ 7–18,5 ] , 14 [ 8,5–19 ] * et 15 [ 6–23 ] * , respectivement ( * P < 0,05vs le groupe 1 ml ) . Le nombre de segments atteints d’hypoesthésie à la piqûre a été , dans les trois sous-groupes de mépivacaïne 1 % , de 10,5 [ 2–22 ] , 10,5 [ 4–17 ] et 11 [ 4–19 ] , respectivement . Les segments du groupe de mépivacaïne 1,5 % ont été de 12 [ 7,5–16 ] , 12 [ 7,5–17 ] et de 11,5 [ 5–22,5 ] , respectivement . Le volume de solution salée n’a pas changé le niveau anesthésique de la mépivacaïne 1 % , mais il a eu un effet sur l’étendue anesthésique de mépivacaïne 1,5 % . Dans les deux groupes , un blocage nerveux différentiel a été provoqué dans les sous-groupes de patients qui ont reçu 5 et 10 ml de solution salée . Conclusion Lorsqu’on administre un gr and volume de solution salée avant l’anesthésique local , on peut obtenir davantage de blocage différentiel et une plus gr and e étendue de l’anesthésie Forty-nine patients , scheduled for transurethral resection of the prostate or a bladder neoplasm on 50 occasions , were studied . The patients were r and omly allocated to one of the two methods of puncture , midline or paramedian . Technical difficulties and the occurrence of complications were recorded . The extent of sensory and motor blockade was also compared . The paramedian approach was associated with a lower frequency of technical problems compared to the midline approach . Statistically significant differences were demonstrated between the two techniques for the following factors : repeated attempts at needle insertion ; difficulty in identification of the epidural space ; resistance to introduction of the catheter ; resistance to injection through the epidural catheter ; and the production of paraesthesiae ( nine patients in the midline group compared to only one patient in the paramedian group , p less than 0.01 ) . The catheter entered a vessel at first in two patients in each group . No significant differences were demonstrated between the groups in the extent of sensory and motor blockade . The study supports the view that the paramedian approach has technical advantages over the midline approach for lumbar epidural analgesia with catheter technique Background The spread of epidural analgesia is facilitated by pregnancy . Changes in the epidural structure during pregnancy may affect the spread of analgesia in pregnant women . To investigate the changes in the epidural space produced by pregnancy , the authors performed epiduroscopy in pregnant women . Methods Using a flexible fiberscope , the authors evaluated the epidural space in 73 women undergoing lumbar epidural anesthesia . Patients were classified into three groups : a nonpregnant group ( n = 21 ) , a first trimester pregnant group ( 8–13 weeks , n = 23 ) , and a third-trimester pregnant group ( 27–39 weeks , n = 29 ) . A 17-gauge Tuohy needle was inserted using the paramedian technique and the loss-of-resistance method with 5 ml air . The epiduroscope was introduced into the lumbar epidural space via the Tuohy needle and was advanced approximately 10 cm in a cephalad direction from the needle tip within the epidural space . The differences in the epidural space among the three groups then was evaluated . Results The epiduroscopy showed that the epidural pneumatic space , after injection of a given amount of air , was narrower and the density of the vascular network greater in the third-trimester group than in the other two groups . The amount of engorged blood vessels was greater in the third and first trimester groups than in the nonpregnant group . The amount of bleeding at the needle tip and the amount of fatty and fibrous connective tissue did not differ among the three groups . Conclusions Epidural blood vessels become engorged in the first trimester ; the density of the vascular networks increase in the third trimester . These changes in the epidural space during pregnancy may affect the spread of epidural analgesia in pregnant women The stiffness on bending of 7 types of epidural catheters was measured with the help of a cantilever beam . 1415 patients scheduled for lithotripsy , requiring epidural anesthesia , were selected and r and omly assigned to receive one of the catheters . The patients were divided into 2 groups according to the resistance to insertion . The incidence of intravenous insertion , subarachnoid location and paresthesia during catheter insertion were assessed . The position of epidural catheters was studied radiographically in 1276 of 1415 patients . There were no significant difference among 7 types of epidural catheters as far as the incidence of intravenous insertion , subarachnoid insertion or straight lying of catheter in epidural space were concerned . When the catheter was hard or pushed against the resistance to insertion , the incidence of paresthesia increased . When the catheter was hard and pushed against the resistance to insertion , transforaminal escape increased . A soft catheter should be chosen to minimize the incidence of paresthesia or transforaminal escape Two techniques of injection for epidural anaesthesia for Caesarean sections were studied . Forty-five patients were r and omly divided into two groups . Patients in Group I received 20 ml of lidocaine two per cent with epinephrine via the needle at a rate of 5 ml.30 sec-1 after a 3 ml test dose . Patients in Group II received the same dose of the same solution in increments of 5 ml injected through a catheter after a 3 ml test-dose . Each increment was injected in one minute with a delay of two minutes between injections . Top-up doses were given in both groups to obtain a T4 sensory level . There was no difference between the two groups in the quality of sensory block before delivery . However , the quality was significantly better in Group II after delivery ( P = 0.02 ) . The incidence of hypotension was 52.2 per cent in Group I and 13.6 per cent in Group II ( P = 0.014 ) . There was no significant difference in maternal and umbilical venous lidocaine concentrations . We conclude that injection in fractional doses is a safer and more efficient technique for epidural anaesthesia for Caesarean section Fifty women in labour were allocated r and omly to receive either air or saline to assist in the identification of the extradural space by the loss of resistance technique . A study volume of 4 ml of air or saline was used before 0.5 % bupivacaine 8 ml and the spread of analgesia was followed for 30 min . The first segment blocked , time of onset , number of blocked segments and height of block were comparable in the two groups . At 30 min , there were eight patients with an unblocked segment in the air group , compared with two in the saline group ( P less than 0.01 ) . All unblocked segments were blocked subsequently by further doses of bupivacaine . We conclude that air is more likely than saline to produce unblocked segments in the initiation of extradural analgesia in labour Thirty-five patients kept in a sitting position for 5 min after a st and ard extradural injection in labour were compared with 54 patients maintained in the left lateral position throughout . The mean upper limit of analgesia was unchanged . A significant shift of the mean lower limit occurred in the sitting patients ( P = 0.05 , two-tailed ) , but contrary to classical teaching this was in a cephalad direction . Successful sacral blockade ( analgesia at S234 ) and asymmetry of blockade occurred in a similar proportion of each group . It was concluded that the sitting position conferred no clinical advantage to patients receiving extradural analgesia in labour Background and Objectives Controversy exists over the choice of the ideal epidural catheter for obstetric use , particularly whether the catheter should have a single terminal hole or three lateral eyes . Methods A r and omized single-blind study of 200 obstetric patients undergoing epidural block for analgesia in labor or for cesarean delivery was undertaken , using either a catheter with a terminal hole or three lateral eyes . The extent and quality of the block was recorded , as well as the presence of any complications . Results The study was ab and oned after 102 patients had been assessed , as the incidence of unsatisfactory blocks with terminal eye catheters was found to be unacceptably high ( 32 % ) , when compared with the lateral eye catheters ( 12 % ) ( P < .05 ) . Four of the terminal eye catheters ( 8 % ) had to be resited compared with one of the lateral eye catheters ( 2 % ) . One case of intravascular injection ( 2 % ) occurred through a terminal eye catheter , despite repeated negative attempts at aspiration . Conclusions The use of terminal eye epidural catheters in our obstetric patients has led to an unacceptably high incidence of both unsatisfactory blocks and catheter replacement . Lateral eye catheters produced better results in our circumstances Purpose To compare the incidence of complications during placement of Arrow ( FlexTip Plus ™ ) and Concord/Portex ™ epidural catheters in parturients receiving continuous epidural analgesia . Methods Two hundred parturients requesting continuous epidural analgesia were prospect ively and r and omly assigned to receive either the Arrow ( FlexTip Plus ™ ) or the Portex epidural catheter . The incidences of paresthesiae , inadvertent venous cannulation and inability to thread the catheter into the epidural space were recorded . Results A total of 222 attempts at epidural placement occurred in the parturients enrolled . The Arrow catheter displayed a lower incidence of paresthesiae ( 3/112vs 39/110,P < 0.0001 ) and venous cannulation ( 0/112vs 11/110,P = 0.0007 ) than did the Portex catheter . The Portex catheter demonstrated a tendency towards increased inability to be advanced into the epidural space ( 5/110vs 0/112,P = 0.057 ) in comparison to the Arrow catheter . When a Portex catheter would not advance into the epidural space ( n = 5 ) , an Arrow catheter was threaded successfully in all five cases without the need to reposition the Tuohy needle . Conclusion Compared with a less flexible catheter , the Arrow decreases the incidence of transient paresthesiae and inadvertent venous cannulation , while improving the ability to thread the catheter into the epidural space . Intravascular injection , transarachnoid migration , and the rare occurrence of epidural haematoma may be further reduced with the use of flexible , soft-tip catheters . RésuméObjectifÉvaluer l’incidence des complications durant l ’ introduction de deux cathéters périduraux , le FlexTip Plus ® d’Arrow et le cathéter de Concord/Portex ® , chez des parturientes nécessitant une analgésie épidurale . MéthodesDeux cents parturientes dem and ant une analgésie péridurale ont été assignées aléatoirement et de façon prospect i ve à deux groupes quant au cathéter utilisé , le FlexTip Plus ® d’Arrow ou le cathéter Portex . On a colligé l’incidence des paresthésies , des canulations veineuses accidentelles et des incapacités à monter le cathéter dans l’espace . RésultatsUn total de 222 essais d ’ introduction de cathéter ont été réalisés chez les parturientes de l’étude . Le cathéter Arrow a présenté une incidence plus faible de paresthésies ( 3/112 vs 39/110,P < 0,0001 ) , de canulations veineuses ( 0/112vs 11/110,P = 0,0007 ) ainsi que d’incapacité à monter le cathéter ( 0/112 vs 5/110,P = 0,057 ) que le cathéter Portex . En outre , dans les cinq cas ou le cathéter Portex n’a pas voulu monter dans l’espace , le cathéter Arrow a été introduit avec succès sans besoin de repositionner l’aiguille de Tuohy . Conclusion Par comparaison avec un cathéter moins flexible , le cathéter d’Arrow diminue l’incidence de paresthésies transitoires et de canulations veineuses accidentelles , tout en améliorant la capacité de monter le cathéter dans l’espace péridural . L’injection intravasculaire , la migration sous arachnoïdienne et la survenue très rare d’un hématome épidural pourraient voir leur incidence encore réduite par l’utilisation de cathéters souples à bout mousse Positioning for placement of an epidural catheter can be quite painful for patients with lower limb injuries . We r and omly allocated 50 patients scheduled for surgery after lower limb injuries for placement of a lumbar epidural catheter in the sitting position with the back in the neutral unflexed position by either the midline or paramedian approach . If the approach failed after two attempts , patients were placed in a flexed-spine position , and the procedure was attempted again . Technical difficulties and complications were recorded . In 17 patients in the midline group , and 1 patient in the paramedian group , it was not possible to insert the needle initially , and a flexed-spine position was required ( P < 0.05 ) . The incidences of resistance to catheter insertion ( eight versus one ) , paresthesia ( seven versus zero ) , and appearance of blood in the catheter ( six versus zero ) were significantly more frequent in the midline compared with the paramedian approach . The midline group also experienced more discomfort than the paramedian group . We conclude that , with the patient sitting with an unflexed spine , it is usually possible to insert an epidural catheter with the paramedian approach Background Although it is generally accepted that inserting epidural catheters 3–4 cm into the epidural space minimizes complications , no prospect i ve r and omized examination of epidural catheter insertion length has been published . Methods Eight hundred healthy parturients requesting epidural analgesia were r and omized to have open‐tip epidural catheters inserted 2 , 4 , 6 , or 8 cm within the epidural space . The incidences of intravenous cannulation , unilateral sensory analgesia , and subsequent catheter dislodgment were recorded . Catheter insertions that result ed in intravenous cannulation or unilateral analgesia were incrementally withdrawn and retested with additional local anesthetic to determine the effectiveness of epidural catheter manipulation . Results Epidural catheters inserted 8 cm within the epidural space were more likely to result in intravenous cannulation . Epidural catheters inserted 2 cm within the epidural space were less likely to result in unilateral sensory analgesia but were more likely to become dislodged . Twenty‐three percent of epidural catheters inserted > 2 cm within the epidural space required manipulation . Epidural catheters inserted 2 or 4 cm required replacement more often than epidural catheters inserted 6 or 8 cm . Ninety‐one percent and 50 % of epidural catheters that result ed in unilateral sensory analgesia and intravenous cannulation , respectively , provided analgesia for labor and delivery after incremental withdrawal . Conclusions Epidural catheters should be inserted either 2 cm when rapid labor is anticipated or 6 cm when prolonged labor or cesarean delivery is likely . Additionally , epidural catheters that result in intravenous cannulation or unilateral sensory analgesia can be manipulated effectively to provide analgesia for labor and delivery Purpose : The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic . The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization performed in three different body positions . — Methods : The study was conducted in 900 ( three groups of 300 ) obstetric patients undergoing continuous epidural analgesia during their labour and who were r and omly allocated to three groups . Epidural catheterization was performed with patients in the sitting , lateral recumbent horizontal , or lateral recumbent head-down position . Results : There was a lower incidence of vessel cannulation when this procedure was performed in the lateral recumbent head-down position ( 2 % ) than in the lateral recumbent horizontal ( 6 % ) and in the sitting position ( 10.7 % ) . Conclusion : Adoption of the lateral recumbent head-down position for the performance of lumbar epidural blockade , in labour at term , reduces the incidence of lumbar epidural venous puncture . RésuméObjectif : La canulation accidentelle et passée inaperçue d’une veine péridurale représente une complication potentiellement dangereuse de l’anesthésie épidurale . La présente étude évalue l’incidence de ponction vasculaire reliée au cathétérisme péridural réalisé selon trois positions corporelles différentes . Méthode : L’étude a été menée auprès de 900 patientes en obstétrique , trois groupes de 300 réparties au hasard , qui recevaient une analgésie épidurale pendant le travail . La mise en place d’un cathéter péridural a été réalisée en position assise , allongée sur le côté ou allongée sur le côté et tête vers le bas . Résultats : L’incidence de ponction vasculaire est plus faible , 2 % , en position allongée avec la tête vers le bas , puis de 6 % en position allongée sur le côté et de 10,7 % en position assise . Conclusion : Pendant le travail dans le cas d’une grossesse à terme , l’adoption de la position allongée sur le côté et tête vers le bas , pour l’administration d’un bloc épidural , réduit l’incidence de ponction veineuse The effect of lateral positioning and the volume of drug injected on the spread of epidural anaesthesia was assessed in 131 healthy parturients . Epidural injection for anaesthesia was done at the L3 - 4 interspace and a catheter was inserted into the epidural space after injection of the drug . The patients were r and omly assigned to four groups . The doses used were 12 ml of bupivacaine 0.25 per cent and 6 ml of bupivacaine 0.5 per cent . Patients were kept in the lateral position in which the block was done ( Groups I and III ) or turned to the opposite side after completion of the epidural injection ( Groups II and IV ) . Sensory levels and maternal assessment of pain relief were determined fifteen to twenty minutes after injection . All assessment s were done by a trained observer who did not know to what group the patient had been allocated . Maintenance of the lateral position after induction of epidural anaesthesia is compatible with satisfactory analgesia for labour . Twelve ml bupivacaine 0.25 per cent provides better analgesia than 6 ml bupivacaine 0.5 per cent although the same mass is injected . The quality of analgesia is improved by turning the patients to the contralateral side after injection of 12 ml bupivacaine 0.25 per cent Seventy patients ( ASA I , ASA II ) , scheduled for a surgical intervention under epidural or combined spinal-epidural anaesthesia , were r and omly allocated to one of two groups . The epidural space was identified by loss of resistance using air , followed by injection in Group A ( 35 patients ) of 10 ml of physiological saline directed cephallad and in Group B ( 35 patients ) by no injection . Thereafter an anaesthetist , different to the one who placed the Tuohy in the epidural space , advanced a catheter up to 10 cm into the epidural space . At each cm of advance the resistance was judged . No significant difference in resistance was found between the groups . The authors conclude that the injection of 10 ml of physiological saline into the epidural space does not facilitate the advancement of an epidural catheter Summary Eighty‐seven pregnant mothers undergoing elective Caesarean section were r and omly allocated either to the full left lateral position ( n = 45 ) or to the supine position with 12 ° left lateral tilt ( n = 42 ) after a combined spinal – epidural ( CSE ) in the sitting position and an initial 2 min in the full right lateral position . Fewer mothers were hypotensive while in the study position [ 29 ( 64 % ) in lateral group vs. 38 ( 90 % ) in the tilted supine group ; p = 0.03 ] . Mothers in the lateral group tended to become hypotensive after turning them back to the tilted supine position immediately before surgery ; hence the number of mothers who were hypotensive from the insertion of the CSE until delivery were similar [ 36 ( 80 % ) vs. 38 ( 90 % ) ] . Mothers in the lateral group needed a lower dose of ephedrine to treat their hypotension while in their study position { median ( interquartile range [ range ] ) 6 ( 0–12 [ 0–36 ] ) mg vs. 12 ( 6–18 [ 0–36 ] ) mg , respectively ; p = 0.04 } but ephedrine requirements were similar overall { 12 ( 6–12 [ 0–36 ] ) mg vs. 12 ( 6–18 [ 0–36 ] ) mg } , respectively . The full left lateral position reduces the incidence of early hypotension compared with the tilted supine position with tilt , and makes it easier to treat Background Multiport epidural catheters are popular ; however , the reliability of the air test has not been evaluated with this catheter design . The authors determined the effectiveness of aspirating for blood and the air test in detecting intravascular multiorifice epidural catheters . Methods Three hundred women in labor underwent placement of a blunt-tip , three-hole , 20-gauge , lumbar epidural catheter . If there were no signs of spinal anesthesia , 3 ml lidocaine or bupivacaine was injected and the patient was observed for signs of spinal anesthesia . If there were no signs of spinal anesthesia , the authors injected 1 ml air through the epidural catheter while listening to the maternal precordium using a Doppler fetal heart rate monitor . Catheters through which blood was aspirated were air-tested and replaced . Patients with air – test-positive , blood – aspiration-negative catheters received 100 mg lidocaine through the catheter and were question ed about toxicity symptoms . The authors injected bupivacaine – fentanyl through aspiration-negative , air – test-negative catheters and recorded the sensory analgesic level 20 min later . Results The authors aspirated cerebrospinal fluid through one catheter and documented intravascular placement in 11 catheters . Results of the air test and blood aspiration were positive for eight catheters . Blood could not be aspirated from one air – test-positive catheter ; perioral numbness developed in the patient after lidocaine injection . Blood was freely aspirated from two air – test-negative catheters . In the remaining 288 catheters , bupivacaine – fentanyl injection produced epidural analgesia in 279 patients and no effect in 9 patients . Conclusions The authors obtained false-negative results with both catheter aspiration and the air test . Fractionating the local anesthetic dose is important when using multiorifice epidural catheters Purpose To determine if injecting 10 mL saline before epidural catheter threading ( pre-cannulation epidural fluid injection ) can decrease the incidence ofiv epidural catheter placement during combined spinal-epidural ( CSE ) labour analgesia . Methods One hundred healthy women requesting CSE labour analgesia with either fentanyl 20 μg or sufentanil 10 μg were prospect ively r and omized to receive either no epidural injection ( dry group , n = 50 ) or epidural 10 mL saline injection ( saline group , n = 50 ) before epidural catheter placement . A nylon multiport catheter was then threaded 3–5 cm into the epidural space and the needle was removed . We diagnosediv catheter placement if blood was freely aspirated , if the mother became tachycardic after injection of epinephrine 15 μg , or if intracardiac air was heard ( using ultrasound ) after injection of air 1.5 mL. Results Intravenous epidural catheter placement occurred in one saline and ten dry group patients ( P < 0.01 ) . No complications of excessive cephalad intrathecal opioid spread ( i.e. , difficulty swallowing , hypoxemia , or respiratory arrest ) occurred . Conclusions Injecting 10 mL or saline through the epidural needle after intrathecal opioid injection and before threading the catheter significantly decreased accidental venous catheter placement without any apparent increase in complications from excessive cephalad intrathecal opioid spread . RésuméObjectifVérifier si l’injection de 10 mL de solution saline avant d’enfiler le cathéter péridural ( injection de liquide pré-insertion ) peut réduire l’incidence de canulation iv du cathéter péridural pendant l’analgésie rachidienne péridurale combinée ( RPC ) pour le travail . MéthodeCent femmes en bonne santé voulant une analgésie RPC , soit avec 20 μg de fentanyl , soit 10 μg de sufentanil , ont été réparties prospect ivement au hasard . Il n’y a pas eu d’injection péridurale dans le groupe témoin ( n = 50 ) mais l’injection péridurale de 10 mL de solution saline dans le groupe salin ( n = 50 ) avant la mise en place du cathéter péridural . Un cathéter de nylon à ouvertures multiples a été ensuite poussé de 3–5 cm à l’intérieur de l’espace péridural et l’aiguille a été retirée . Laspiration libre de sang , la tachycardie de la mère suivant l’injection de 15 μg d’épinéphrine ou la présence d’air intracardiaque , décelée par ultrasons après l’injection de 1,5 mL d’air , indiquaient la canulation iv du cathéter . RésultatsLa canulation intraveineuse du cathéter péridurai est survenue chez une patiente du groupe salin et dix patientes témoins ( P < 0,01 ) . Aucune complication causée par la diffusion marquée de l’opioïde intrathécal en direction céphalique ( comme la déglutition difficile , l’hypoxémie ou l’arrêt respiratoire ) n’a été notée . Conclusion L’injection , par l’aiguille péridurale , de 10 mL de solution saline après l’injection intrathécale d’opioïde et avant l’insertion du cathéter a fait diminuer significativement la canulation place veineuse accidentelle du cathéter , sans augmentation apparente de complications causées par la diffusion marquée d’opioïde intrathécal en direction céphalique OBJECTIVE To determine whether two vs 10 mL of saline injected into the epidural space affects the subsequent spread and quality of epidural analgesia in parturients . DESIGN R and omized , double-blinded , placebo-controlled study . SETTING Delivery room . PATIENTS 105 ASA physical status I and II parturients requesting epidural analgesia . INTERVENTIONS After identification of the epidural space by the loss-of-resistance technique using normal saline , two mL of saline was then injected into the epidural space in the 2-mL group ( n = 53 ) and 10 mL in the 10-mL group ( n = 52 ) . Five minutes after the test dose , patients received 10 mL of bupivacaine ( 0.1 % ) with fentanyl two microg mL(-1 ) . MEASUREMENTS 25 minutes after the initial bolus of bupivacaine and fentanyl , spread of block , subsequent pain relief , and influence of the volume of the injected saline on the ease of epidural catheter insertion and on the incidence of blood vessel trauma and paresthesia were evaluated . RESULTS The total number of dermatomes blocked for cold and pinprick sensation in the 10-mL group was significantly more than in the 2-mL group ( 19 [ 6 - 29 ] vs 15 [ 4 - 27 ] for cold sensation , P = 0.000 ; and 15 [ 3 - 29 ] vs 11.5 [ 3 - 26 ] for pinprick sensation , P = 0.001 ) . However , the visual analog pain scale and need for supplemental analgesia were similar between the two groups . The epidural catheter was easily inserted in 94.2 % of the 2-mL group and 100 % of the 10-mL group . The incidence of blood vessel trauma was low and the incidence of paresthesia was high without any significant difference between the two groups . CONCLUSIONS 10 mL saline was associated with a higher total number of dermatomes blocked for both cold and pinprick sensation than the two mL saline . However , the pain relief was adequate in both groups , and two mL saline was as effective as the 10 mL in the ease of catheter insertion and prevention of intravascular cannulation The ideal technique for identifying the epidural space remains unclear . Five-hundred-forty-seven women in labor who requested epidural analgesia were r and omly allocated to three groups according to the technique by which the epidural space was identified : 1 ) loss-of-resistance with air ( air ; n = 180 ) , 2 ) loss-of-resistance with lidocaine ( lidocaine ; n = 185 ) , and 3 ) loss-of-resistance with both air and lidocaine ( air-plus-lidocaine ; n = 182 ) . We assessed ease of epidural catheter insertion , characteristics of the blockade , quality of analgesia , and complications . The inability to thread the epidural catheter occurred in 16 % of the air , 4 % of the lidocaine , and 3 % of the air-plus-lidocaine patients ( P < 0.001 ) . More patients from the air group had unblocked segments ( 6.6 % versus 3.2 % and 2.2 % , respectively ; P < 0.02 ) . The incidence of accidental dural puncture was greater in the air group ( 1.7 % versus 0 % in the other two groups ; P < 0.02 ) . Pain scores , time to onset of analgesia , upper sensory level , motor blockade , and the incidence of hypotension , transient neurological deficits , postpartum urinary retention , and postdural puncture headache were comparable . Identification of the epidural space with air was more difficult and caused more dural punctures than with lidocaine or air plus lidocaine . Additionally , sequential use of air and lidocaine had no advantage over lidocaine alone The purpose of this study was to compare two epidural catheters — the Portex ® epidural catheter and Vas-Cath ® catheter . One hundred and fifty patients in labour who received epidural anaesthesia were selected and either one or the other catheter was used , based on r and om assignment . Ease of insertion , maintenance and removal of the catheter were assessed , as was the incidence of blood return and paraesthesiae during epidural catheter insertion . There were no significant differences between the catheters as far as insertion , maintenance and removal were concerned . However , the incidence of paresthesiae was 44 per cent with the Porlex ® and 24 per cent with Vas-Cath ® catheters ( p < 0.008 ) . The incidence of blood vessel trauma was 12 per cent with the Portex ® and 6.7 per cent with the Vas-Cath ® catheter ( p = NS ) . Choice of epidural catheter is a factor to be considered in minimizing the incidence of blood vessel trauma or paresthesiae . RésuméLe but de cette étude était de comparer deux cathéters périduraux — le Portex et le Vas-Cath . On a installé de façon aléatoire ľun ou ľautre des cathéters chez 150 patientes en travail qui recevaient une anesthésie péridurale , On a évalué la facilité ďinsertion , le maintien et le retrait du cathéter ainsi que ľincidence du retour sanguin et de la paresthésie durant ľinsertion du cathéter péridural . Aucune différence significative n’existait entre les cathéters quant à ľinsertion , le maintien et le retrait . Cependant , ľincidence de paresthésie était de 44 pour cent avec le Portex et de 24 pour cent avec le Vas-Cath ( p < 0.008 ) . Ľincidence de traumatisme au vaisseau sanguin était de 12 pour cent avec le Portex et de 6.7 pour cent avec le Vas-Cath ( p = NS ) . Le choix du cathéter péridural est un facteur à considérer afin de minimiser ľincidence de traumatisme vasculaire et de paresthésie Adverse fetal heart rate ( FHR ) changes suggestive of fetal hypoxia are seen in patients with normal term pregnancies after initiation of epidural block for labour analgesia . It was our hypothesis that , in some parturients , these changes were a consequence of concealed aortocaval compression result ing in decreased uterine blood flow . We expected that the full lateral position compared with the wedged supine position would provide more effective prophylaxis against aortocaval compression . To test our hypothesis we studied the role of maternal positioning on FHR changes during onset of epidural analgesia for labour . Eighty-eight ASA Class I or II term parturients were r and omized into two groups : those to be nursed in the wedged supine position and those to be nursed in the full lateral position during induction of an epidural block . External FHR monitoring was employed to assess the fetal response to initiation of labour epidural analgesia . Epidural catheters were sited with the parturients in the sitting position and the patients then assumed the study position . After a negative test dose , a st and ardized regimen of bupivacaine 0.25 % was employed to provide labour analgesia . The quality and efficacy of the block were assessed using VAS pain scores , motor block scores and sensory levels . The results demonstrated that there was no difference in the quality of analgesia provided nor in the incidence of asymmetric blocks . There was no difference in the observed incidence of FHR changes occurring during the initiation of the epidural block . ( ABSTRACT TRUNCATED AT 250 WORDS Purpose To examine the effect of modifying the interval between administration of saline used during the loss of resistance ( LOR ) method and local anesthetic on epidural anesthetic level and its quality . Methods Seventy-three patients who received thoracic epidural anesthesia were r and omly allocated into three groups ; the 2 , 5 and 10 min groups , according to the interval between the administration of saline and 8 ml mepivacaine 1.5 % . Fifteen minutes after the mepivacaine injection , the dermatome level of hypesthesia was determined by an individual blinded to the interval . Results When the saline-anesthetic interval was prolonged , the hypesthetic levels for coldness and pinprick were decreased . The number of spinal segments with hypesthesia for coldness were 15 [ 12–20 ] # , 12.5 [ 10.5–22.5 ] # # and 10.5 [ 6.5–15.5 ] # # # in the 2 , 5 and 10 min groups , respectively ( median [ range ] , # P < 0.05vs the 5 min group , # # P < 0.05vs the 10 min group , # # # P < 0.05vs the 2 min group ) . The number of spinal segments with hypesthesia for pinprick were 13.5 [ 11–18 ] # , 11 [ 7.5–20.5 ] # # and 10 [ 5.5–13 ] # # # in the 2 , 5 and 10 min groups , respectively . There were differences in all groups between the number of segments with hypesthesia for coldness and pinprick elicited . Conclusion The interval between the administration of saline and local anesthetic alters the anesthetic level and quality of epidural analgesia . RésuméObjectifExaminer l’effet de la modification de l’intervalle entre l’administration de solution salée et d’anesthésique local sur le niveau anesthésique péridural et ses caractéristiques , lorsqu’on utilise la méthode de perte de résistance (PDR).MéthodeSoixante-treize patients qui ont reçu une anesthésie péridurale thoracique ont été répartis au hasard en trois groupes de 2 , 5 et 10 min , selon l’intervalle entre l’administration de la solution salée et de 8 ml de mépivacaïne à 1,5 % . Quinze minutes après l’injection de mépivacaïne , le niveau du dermatome atteint d’hypoesthésie a été déterminé par une personne qui ne connaissait pas la durée de l’intervalle . RésultatsQu and l’intervalle solution salée-anesthésique était prolongé , les niveaux hypoesthésiques des sensations de froid et de piqûre ont été abaissés . Le nombre de segments médullaires qui présentaient de l’hypoesthésie au froid ont été de 15 [ 12–20 ] # , 12,5 [ 10,5–22,5 ] # # et de 10,5 [ 6,5–15,5 ] # # # dans les groupes de 2 , 5 et 10 min , respectivement , ( médiane [ étendue ] , # P < 0,05vs le groupe de 5 min , # # P < 0,05 vs le groupe de 10 min , # # # P < 0,05 vs le groupe de 2 min ) . Le nombre de segments médullaires atteints d’hypoesthésie à la piqûre ont été de 13,5 [ 11–18 ] # , 11 [ 7,5–20,5 ] # # et de 10 [ 5,5 - 13 ] # # # dans les groupes de 2 , 5 et 10 min , respectivement . Il y a eu des différences entre tous les groupes quant au nombre de segments atteints d’hypoesthésie provoquée au froid et à la piqûre . Conclusion L’intervalle entre l’administration d’une solution salée et d’un anesthésique local modifie le niveau anesthésique et la qualité de l’analgésie péridurale We evaluated the radiopacity and usefulness of the two radiopaque epidural catheters , one by Portex CO . Ltd. , and the other Flex Tip Plus with a stainless coil by Arrow Japan Co. Ltd. The Portex catheter ( Group A ) or the Arrow catheter ( Group B ) was inserted through a single epidural space from Th7 to Th12 in 20 patients each . The two plain chest X-rays , one for the lung and the other for the catheter , were taken in all patients after surgery . We compared the two groups and examined whether the identification of the catheter was possible or not in the two kinds of X-rays , whether the catheter had gone straight or not , and whether the insertion of the catheter had been easy or difficult . The course of the catheter was identified easily in 1 case of Group A and 4 cases of Group B but was not identified at all in 10 cases of Group A and 8 cases of Group B. There were no differences between the two groups in the number of patients in whom the catheter was easily inserted , identified , or placed straight . Therefore , the usefulness of the two catheters in terms of insertion and identification of its course was not different One hundred women were r and omly allocated to the left lateral , Oxford or sitting position for induction of combined spinal‐epidural anaesthesia for Caesarean section using 2.5 ml hyperbaric bupivacaine 0.5 % and 10 μg fentanyl . Women in the left lateral were then turned to the right lateral position ; women in the Oxford position were turned to the same position on their opposite side ; and women in the sitting group were turned to the supine left tilt position . Women remained in these positions until ready for surgery , which was conducted in the supine position with a wedge placed under the right hip . Ephedrine requirements before re‐positioning for surgery were less in the sitting position than in the other two positions : median ( IQR [ range ] ) doses for the lateral , Oxford and sitting groups were 21 ( 12–30 [ 6–48 ] ) , 18 ( 7.5–24 [ 6–48 ] ) and 12 ( 6–21 [ 6–42 ] ) mg , respectively ; p = 0.04 . Sensory block to touch sensation at the T5 dermatomal level was most quickly achieved in the lateral position with median ( IQR [ range ] ) block onset times for the lateral , Oxford and sitting groups of 9 ( 6–13 [ 4–30 ] ) , 15.5 ( 9–22 [ 4–34 ] ) and 14 ( 9–18[6–36 ] ) min , respectively ; p = 0.004 . In the Oxford position , more epidural catheters required dosing to achieve a sensory block of T5 before surgery : the number of patients ( proportion ) bolused in the lateral , Oxford and sitting groups was 1 ( 3 % ) , 7 ( 22 % ) and 1 ( 3 % ) , respectively ; p = 0.01 . We did not demonstrate any advantage in using the Oxford position for combined spinal‐epidural anaesthesia for elective Caesarean section Combined spinal-epidural anesthesia ( CSE ) is a popular technique for cesarean delivery . Regional blocks in obstetrics are often performed with the parturient in the sitting position because the midline may be recognized more easily than in the lateral decubitus position . When conventional spinal anesthesia is performed in the sitting position , the patient is placed supine immediately after drug injection . In contrast , when CSE is performed with the woman sitting , there is a delay in assuming the supine position because of epidural catheter placement , which may affect the incidence of hypotension . Healthy women , at term of pregnancy , about to undergo an elective cesarean section under CSE , were r and omly assigned to the sitting or lateral recumbent position for initiation of the block . All parturients were given 1000 mL of lactated Ringer 's solution in the 15 min preceding induction and an additional 300 - 500 mL while the actual block was being performed . On completion of the CSE , they were turned to the supine position with left uterine displacement . A second anesthesiologist , blinded to the woman 's position during CSE , evaluated the sensory level of anesthesia , maternal heart rate , blood pressure , oxygen saturation , need for ephedrine , and occurrence of nausea and vomiting . Results are expressed as mean + /- SD . Twelve women were studied in the sitting group and 10 were studied in the lateral recumbent group . The severity and duration of hypotension were greater in those parturients who had CSE induced in the sitting ( 47 % + /- 7 % and 6 + /- 3 min , respectively ) compared with the lateral recumbent position ( 32 % + /- 14 % and 3 + /- 2 min , respectively ) . Women in the sitting group also required twice as much ephedrine ( 38 + /- 18 mg ) to correct hypotension compared with the other group ( 17 + /- 12 mg ) . In conclusion , the severity and duration of hypotension were greater when CSE was induced in the sitting compared with the lateral decubitus position . Implication s : We studied the induction of combined spinal-epidural anesthesia ( CSE ) in the sitting versus lateral recumbent positions in healthy women undergoing a scheduled cesarean delivery . The severity and duration of hypotension were greater when CSE was induced in the sitting position . Thus , the position used for induction of CSE should be among the factors considered when there is greater maternal or fetal risk from hypotension . ( Anesth Analg 1998;87:614 - 8 This study examined whether air or saline , used for the loss-of-resistance ( LOR ) technique , result ed in a difference in pain relief or adverse events for laboring parturients . Previous studies had mixed findings regarding the onset of analgesia and subsequent pain relief . Research questions were as follows : Is there difference in analgesic onset for patients receiving air vs saline during the LOR technique ? Do women receiving the air method for LOR experience any difference in the quality of pain relief from that of women receiving saline ? Is there any difference in the incidence of analgesic distribution or segmental pain relief in women receiving the air vs the saline method ? Is there any difference in the incidence of adverse effects in women receiving air vs saline during the LOR technique ? This was an experimental , prospect i ve study with 50 women . Subjects were r and omized to receive air or saline . The visual analogue scale was used to measure pain . A dermatome level recorded the spread of analgesia . No significant differences were found between groups for onset or quality of analgesia . There was a significant increase in the number of subjects who experienced segmental blocks after receiving air during the LOR technique We prospect ively studied the incidence of concealed aortocaval compression in parturients at term during identification of the extradural space . Forty ASA I or II parturients , at term and in active labour , who requested extradural analgesia were r and omly allocated to one of two groups . Parturients in the first group ( n = 22 ) were positioned in the left lateral decubitus position and those in the second group ( n = 18 ) were in the sitting position . Cardiac output ( CO ) was recorded at one-minute intervals for five minutes before extradural catheter placement ( supine position with a 15 ° wedge under the right side ) , and during and thereafter for five minutes ( in the supine wedged position ) , using the BoMED NCCOM3-R7 thoracic electrical bioimpedance ( TEB ) monitor . The average of five COTEB recordings before positioning the patient were compared with the average of five COTEB measurements during and after extradural space identification . A change of > 25 % COTEB was considered beyond machine variability . Upper limb arterial pressure was recorded at one-minute intervals . In the left lateral decubitus position , 17 of 22 patients demonstrated a > 25 % reduction in COTEB compared with five of 18 patients in the sitting position ( X2,P < 0.01 ) . The percentage change in COTEB in the lateral decubitus position ( −29.8 % , 95 % CI −17 % to −44 % ) was greater than the sitting position ( −9.8 % , 95 % CI + 36 % to −32 % ) ( P < 0.01 ) . A decreased incidence of aortocaval compression during identification of the extradural space was demonstrated in the sitting position when compared with the left lateral decubitus position . RésuméDe façon prospect i ve , nous avons recherché l’incidence de la compression de l’aorte abdominale et de la veine cave inférieure chez de parturientes à terme pendant le repérage de l’espace péridural . Quarante patientes ASA I ou II à terme ou en travail qui désiraient une anesthésie péridurale ont été distribuées au hasard à un de deux groupes . Le parturientes du premier groupe ( n = 22 ) ont été positionnées en décubitus latéral gauche et celles du deuxième groupe ( n = 18 ) en position assise . Le débit cardiaque ( DC ) fut enregistré à la minute pendant cinq minutes avant la mise en place du catheter péridural ( décubitus dorsal avec un coin soulevant le côté droite de 15 ° ) , pendant et après pour cinq minutes ( toujours en décubitus avec surélévation ) avec un moniteur de bioimpédance thoracique électrique Bomed CCOM3- R7 ( moniteur TEB ) . La moyenne de cinq mesures du DCTEB avant le positionnement de la patiente a été comparée avec la moyenne de cinq mesures enregistrées pendant et après le repérage de l’espace épidural . On a considéré qu’un changement de plus de 25 % du DCTEB dépassait la variabilité de l’appareil . La pression artérielle a été mesurée au membre supérieur à chaque minute . En décubitus latéral , 17 des 22 patientes ont montré une baisse > 25 % de DCTEB en comparaison avec 5 de 18 patientes en position assise ( X2,P < 0,01 ) . Le pourcentage de changement de DCTEB en décubitus latéral ( - 29,8 95 % CI −17 % à −44 % ) est plus gr and qu’en position assise ( - 9,8 , 95 % CI + 36 % à −32 % ) ( P < 0,01 ) . On a donc constaté une baisse de l’incidence de la compression de l’aorte abdominale et de la veine cave inférieure pendant la repérage de l’espace péridural en position assise comparativement au décubitus latéral gauche Background and objective : The purpose of this study was to compare the characteristics of epidural catheter insertion via the midline or the paramedian approach with regard to ease of catheter insertion , incidence of paraesthesias and efficacy of epidural block . In addition to the type of approach , the prognostic value of Patients characteristics variables with regard to the incidence of paraesthesias was assessed . Methods : Thirty patients scheduled for surgery under epidural anaesthesia were r and omly assigned to one of two groups of 15 patients each . Epidural anaesthesia was performed via a midline or paramedian approach using loss of resistance to saline . Variables measured were : time needed to identify the epidural space , time needed for and ease of epidural catheter insertion and the incidence of paraesthesias . After completion of these observations , epidural anaesthesia was established with 150 mg ropivacaine 1 % . Efficacy of the epidural block was assessed by the need for intraoperative analgesics and by the patient on a three‐point scale ( good/fair/poor ) . Results : Quality of sensory blockade was adequate in both groups . Catheter insertion was significantly faster using the paramedian approach . The difference between the two approaches with regard to the incidence of paraesthesias was not significant , however , there was a trend towards more paraesthesias in the midline group . In the multivariate analysis , type of approach was an independent significant predictor of paraesthesias and we found a trend towards a higher incidence of paraesthesias in female patients . Conclusions : Catheter insertion was faster in the paramedian group and we found a trend towards a higher incidence of paraesthesias with the midline approach Epidural catheter placement offers flexibility in block management . However , during epidural catheter insertion , complications such as paresthesia and venous and subarachnoid cannulation may occur , and suboptimal catheter placement can affect the quality of anesthesia . We performed this prospect i ve , r and omized , double-blind study to assess the effect of a single-injection dose of local anesthetic ( 20 mL of 2 % lidocaine ) through the epidural needle as a priming solution into the epidural space before catheter insertion . We r and omized 240 patients into 2 equal groups and measured the quality of anesthesia and the incidence of complications . In the needle group ( n = 100 ) , catheters were inserted after injection of a full dose of local anesthetic through the needle . In the catheter group ( n = 98 ) , the catheters were inserted immediately after identification of the epidural space . Local anesthetic was then injected via the catheter . We noted the occurrence of paresthesia , inability to advance the catheter , or IV or subarachnoid catheter placement . Sensory and motor block were assessed 20 min after the injection of local anesthetic . Surgery was initiated when adequate sensory loss was confirmed . In the catheter group , the incidence of paresthesia during catheter placement was 31.6 % compared with 11 % in the needle group ( P = 0.00038 ) . IV catheterization occurred in 8.2 % versus 2 % of patients in the catheter and needle groups , respectively ( P = 0.048 ) . More patients in the needle group had excellent surgical conditions than the catheter group ( 89.6 % versus 72.9 ; P < 0.003 ) . We conclude that giving a single-injection dose via the epidural needle before catheter placement improves the quality of epidural anesthesia and reduces catheter-related complications Background and Objectives Identification of the epidural space is often performed using the loss-of-resistance technique ( LOR ) , commonly with air or saline . The effect of air or saline on the quality of labor epidural analgesia has not been adequately studied . Methods Women who requested labor epidural analgesia were r and omly assigned to 1 of 2 groups depending on the syringe contents used for the LOR technique and injected into the epidural space . In the air group ( n = 80 ) the anesthesiologist used 2 mL of air , and in the saline group ( n = 80 ) the anesthesiologist used 2 mL of 0.9 % saline . After LOR was obtained , a multiorifice epidural catheter was threaded 5 cm into the epidural space and 13 mL of bupivacaine 0.25 % was administered in divided doses . The success of the epidural block was determined by asking the patient if she required additional medication 15 minutes later . The occurrence of paresthesias and intravascular or subarachnoid catheters was noted . Results In the air group , 36 % of patients requested additional pain medication , and in the saline group 19 % requested additional medication ( P = .022 ) . We were not able to find a statistically significant difference between groups in the incidence of paresthesias ( 42 % air v 51 % saline ) , intravascular catheters ( 5 % air v 8 % saline ) , or subarachnoid catheters ( 0 in both groups ) . Conclusions Using 0.9 % saline for the LOR technique is associated with better analgesia as compared with air for labor analgesia , and this advantage should be considered when selecting the syringe contents for the LOR technique This study was undertaken to analyze the effect of posture on the spread of hyperbaric bupivacaine in pregnant women using a combined spinal extradural technique , and to assess the quality of analgesia provided by 10 mg bupivacaine when using this technique . Fifty parturients undergoing elective Caesarean section under regional anaesthesia were r and omly allocated to receive 2.0 ml hyperbaric bupivacaine 0.5 % in either the sitting or left lateral position . Spinal injection was performed with a 27 gauge , 120 mm long spinal needle using a single space combined spinal extradural technique . The onset time to analgesia at T4 , and grade 3 motor block was on average 7.7 min and 6.9 min respectively in the lateral group , compared with 10.8 min ( P < 0.05 ) and 9.4 min ( P < 0.05 ) in the sitting group . Nine women in the sitting group and one woman ( P < 0.05 ) in the lateral group required epidural supplementation . Hypotension occurred in 48 % of the parturients in the lateral group and in 13 % ( P < 0.05 ) of the parturients in the sitting group . Nausea was noted in 61 % of the parturients in the lateral group and in 22 % ( P < 0.05 ) of the parturients in the sitting group . There was no difference between the two groups in neonatal outcome . Overall , the position of the patient during induction of spinal anaesthesia does influence the rate of onset of analgesia and motor blockade . Injection of 10 mg hyperbaric bupivacaine in the sitting position would not provide adequate analgesia for Caesarean section when using a single space combined spinal extradural technique . RésuméCette étude vise à évaluer : 1 ) l’effet de la position sur la dispersion , chez la parturiente , de la bupivacaine pendant une technique combinant la rachianesthésie à l’épidurale , 2 ) la qualité de l’anesthésie produite par bupivacaine 10 mg avec cette technique . Cinquante parturientes programmées pour césarienne sont réparties au hasard pour recevoir de la bupivacaine hyperbare 0.5 % 2.0 ml en position latérale gauche ( groupe latéral ) ou assise ( groupe assis ) . L’injection rachidienne est réalisée avec une aiguille 27 G de 120 mm de longueur insérée dans l’espace choisi pour la technique combinée rachi- épidurale . La vitesse d’installation jusqu’à l’analgésie au niveau T4 , et le bloc moteur de grade 3 sont en moyenne de 7.7 min et 6.9 min respectivement dans le groupe latéral , comparativement à 10.8 ( P < 0.05 ) et 9.4 min dans le groupe assis ( P < 0.05 ) . Neuf patientes du groupe assis et une seule ( P < 0.05 ) du groupe latéral ont besoin d’un supplément épidural . De l’hypotension survient dans 48 % du groupe latéral et dans 13 % du groupe assis ( P < 0.05 ) . On retrouve de la nausée dans 61 % du groupe latéral et dans 22 % du groupe assis ( P < 0.05 ) . L’état du nouveau- né est identique dans les deux groupes . En général , la position de la parturiente pendant l’induction de la rachianesthésie a une influence sur la rapidité d’installation de l’analgésie et du bloc moteur . L’injection de bupivacaïne hyperbare 10 mg en position assise ne produit pas une analgésie satisfaisante pour la césarienne qu and on utilise la technique combinée rachi-épidurale administrée dans le même espace BACKGROUND Anesthetically , epidural neural blockade is widely used in the fields of surgery and obstetrics as well as in diagnosis and management of acute and chronic pain . However , inadvertent epidural venous puncture might be a serious problem , or even life-threatening particularly when drug is erronaneously injected and prompt diagnosis is not made correct and treatment is not instituted . Although many anesthesiologists suggested that injection of fluid into the epidural space before catheter insertion could prevent an epidural venous puncture , some others did not agree to it . This study aim ed a assess the effect of injection of different volumes of saline into the epidural space before catheter insertion on the incidence of epidural venous puncture . METHODS Three hundred ASA I or II patients receiving Extracorporeal Shock Wave Lithotripsy ( ESWL ) were r and omly divided into three groups : group A ( no saline ) , group B ( 5 ml of saline ) and group C ( 10 ml of saline ) . After the injection of different volume of saline into the epidural space , an epidural catheter was inserted into the epidural space via a Touhy needle . The incidence of epidural venous puncture in each group was compared . RESULTS The incidence of epidural venous puncture in group A and B was 14 % and 11 % , respectively . However , the incidence in group C ( 1 % ) was significantly lower than the other two groups . CONCLUSIONS Our results suggest that injection of 10 ml saline into the epidural space before catheter insertion could significantly diminish the incidence of epidural venous puncture RésuméObjectifL’effet de la position sur la distribution de l’anesthésie épidurale et sur le délai d’installation n’ont pas été bien documentés . La présente étude est entreprise pour évaluer l’effet de la position de Trendelenburg modifiée sur la distribution de l’anesthésie épidurale pendant la césarienne . MéthodesSept cent trente-neuf parturientes ont reçu une anesthésie épidurale pour une césarienne élective ou urgente . Divisées en deux groupes , dans une étude r and omisée et contrôlée , toutes les patientes ont reçu 20 mL de lidocaïne à 2 % administrée avec une aiguille épidurale 19 G , la technique st and ard dans notre établissement . Le premier groupe a été placé en position de Trendelenburg à 15 ° , la tête élevée à 10 ° et le deuxième en position horizontale . Le délai d’installation et le niveau de l’anesthésie , les signes vitaux de la mère , l’indice d’Apgar ont été évalués dans les deux groupes . RésultatsLa pression artérielle , la fréquence cardiaque , la saturation du sang artériel en oxygène , et l’indice d’Apgar n’ont pas présenté de différence significative intergroupe selon les positions de Trendelenburg modifiée ou horizontale . Les résultats montrent des différences significatives de délai d’installation ( environ quatre minutes plus rapide dans le groupe en position de Trendelenburg modifiée ) ( P < 0,001 ) et d’atteinte d’un bloc sensoriel au niveau T5 entre les groupes dans les positions Trendelenburg modifiée et horizontale ( 97,5 % contre 42,8 % respectivement ) . Conclusion Cette étude démontre que la position de Trendelenburg modifiée a un effet significatif sur l’étendue de l’anesthésie épidurale et qu’elle peut être utilisée sans risque chez les parturientes à terme , c and i date s à la césarienne urgente ou élective . Abstract Purpose The effect of position on the spread and the onset time of epidural anesthesia has not been well documented . This study was undertaken to assess the effect of modified Trendelenburg position on the spread of epidural anesthesia for Cesarean section . Methods Seven hundred thirty-nine parturients underwent epidural anesthesia for elective or emergent Cesarean section . Patients were divided into two groups in a r and omized-controlled study . All patients received 20 mL of 2 % lidocaine injected through a 19 G epidural needle , a st and ard technique in our institution . During induction of epidural anesthesia , the first group was placed in 15 Trendelenburg with 10 head-up position and the second in the horizontal position . The onset time and the level of anesthesia , patients ’ vital signs , and Apgar score were recorded in both groups . Results There were no significant differences in vital signs , oxygen saturation and Apgar score between the two groups . The results show significant differences in the time of onset ( on average four minutes faster in the modified Trendelenburg position group ) ( P < 0.001 ) , and in achieving T5 level sensory blockade ( 97.5 % vs 42.8 % ) between the modified Trendelenburg and horizontally positioned pregnant women . Conclusion This study demonstrates that the modified Trendelenburg position has a significant effect on the spread and the onset time of single shot epidural anesthesia , and can be used safely in term parturients for emergency or elective Cesarean section Complications can occur during epidural placement for women in labor . As many as 23 % of epidural anesthetics may not provide satisfactory analgesia . The cause of this may be technical . This study was undertaken to determine the optimal distance that a multiorifice catheter should be threaded into the epidural space to maximize analgesia and minimize complications . One hundred women in labor were enrolled in this prospect i ve , r and omized , and double-blind study . Patients were r and omly assigned to have the epidural catheter threaded 3 , 5 , or 7 cm into the epidural space . After placement of the catheter and administration of a test dose with 3 mL of 0.25 % bupivacaine , an additional 10 mL of 0.25 % bupivacaine was administered in two divided doses . Fifteen minutes later , the adequacy of the analgesia was assessed by a blinded observer . We found that catheter insertion to a depth of 7 cm was associated with the highest rate of insertion complications while insertion to a depth of 5 cm was associated with the highest incidence of satisfactory analgesia . For women in labor who require continuous lumbar epidural anesthesia , we recommend threading a multiorifice epidural catheter 5 cm into the epidural space . ( Anesth Analg 1995;81:301 - 4 This study was undertaken to investigate the outcome of epidural catheter insertion in the sitting or lateral position in mothers during labour . An initial prospect i ve r and omised study period ( 144 patients ) suggested that the sitting position offered some superiority over the lateral in terms of technical ease of insertion . It was concluded , by minimising the subjective aspects in a follow‐up , prospect i ve nonr and omised study period ( 152 patients ) , that the determining factor lies in the skill and experience of the anaesthetist . There was no significant difference in complication rates or maternal discomfort between the two positions in either study period Purpose The unintentional and unrecognized cannulation of an extradural vein is a potentially serious complication of an epidural anesthetic . The present study was undertaken to assess the incidence of blood vessel puncture related to epidural catheterization in three different body positions , in a cohort of morbidly obese parturients , following the completion of a similar study published in 2001 from which such parturients were excluded . Methods The study was conducted in 450 ( three groups of 150 ) morbidly obese , obstetric patients undergoing continuous epidural analgesia during labour . Epidural catheterization was performed on patients r and omized to the sitting , lateral recumbent horizontal , or lateral recumbent head-down position . Results There was a lower incidence of vessel cannulation when this procedure was performed in the lateral recumbent head-down position [ 1.3 % ; body mass index ( BMI ): 37.0 ] than in the lateral recumbent horizontal [ 12.9 % ; BMI : 38.0 ] and in the sitting position [ 12.0 % ; BMI : 38.0 ] . The incidence of accidental subarachnoid puncture was 2 % , 1.3 % and 2 % respectively , in these same positions . Conclusion Adoption of the lateral recumbent head-down position for the performance of lumbar epidural blockade , in labour at term , reduces the incidence of lumbar epidural venous puncture in these obese parturients . RésuméObjectifLa canulation accidentelle et inaperçue d’une veine extradurale est une complication grave possible de l’anesthésie épidurale . Nous avons voulu évaluer l’incidence de ponction vasculaire reliée à la cathétérisation épidurale selon trois différentes positions du corps de parturientes avec obésité morbide , pour donner suite à une étude similaire publiée en 2001 et de laquelle ces parturientes avaient été exclues . MéthodeL’étude a été menée chez 450 ( trois groupes de 150 ) patientes d’obstétriques très obèses devant subir une analgésie épidurale continue pendant le travail obstétrical . La cathétérisation a été réalisée chez les patientes r and omisées pour adopter la position assise , décubitus latéral ou Trendelenburg latéral . RésultatsL’incidence de canulation vasculaire était plus faible en position de Trendelenburg latéral [ 1,3 % ; indice de masse corporelle ( IMC ) : 37,0 ] qu’en décubitus latéral [ 12,9 % ; IMC : 38,0 ] ou en position assise [ 12,0 % ; IMC : 38,0 ] . L’incidence de ponction sousarachnoïdienne était de 2 % , 1,3 % et 2 % respectivement , dans ces mêmes positions . Conclusion L’adoption de la position de Trendelenburg latéral pour réaliser le bloc épidural lombaire , au terme du travail , réduit l’incidence de ponction veineuse épidurale lombaire chez ces patientes obèses We compared midline approach with paramedian approach for combined spinal-epidural anesthesia ( CSEA ) by needle through needle technique . Seventy patients undergoing elective gynecological surgery received CSEA with a 27 G Whitacre spinal needle , which protrudes 12 mm beyond the tip of the Tuohy needle . The successful subarachnoid puncture with first attempt was noted in 33 patients ( 94 % ) of midline group ( M group ) , in 31 patients ( 89 % ) of paramedian group ( P group ) . At the subarachnoid puncture , skin to epidural space distance ( 43.2 mm vs 53.4 mm ) and protrusion length of spinal needle ( 5.5 mm vs 8 mm ) were significantly longer in the P group than in the M group . Abdominal radiography revealed the flexion of epidural catheter in 19 patients ( 54 % ) of M group and in 2 patients ( 6 % ) of P group . The choice of midline or paramedian approach for CSEA did not affect the success rate of the subarachnoid puncture , but paramedian approach required longer protrusion length of the spinal needle than midline approach . To raise the success rate of subarachnoid puncture by paramedian approach , a long protruded spinal needle is recommended The clinical usefulness of Combined Spinal-Epidural ( CSE ) needles , Portex Spinal/Epidural set ( P needles ) and Hakko Disposable Needles set type H ( H needles ) was compared on 30 patients undergoing elective orthopedic lower limb surgeries . Although the calibers of the epidural needles were a little different , both needles were introduced quite easily in the epidural space . The spinal needles were inserted successfully to the subarachnoid space in 27 out of 30 cases by the P needles and 23 out of 30 cases by the H needles . The average trial times for successful insertion of the spinal needles were 1.3 and 2.6 by the P needles and the H needles , respectively . this was statistically significant ( P < 0.05 ) . Adequate spinal anesthesia was established in 26 patients ( 87 % ) and 19 patients ( 63 % ) by the P needles and the H needles , respectively . One case of the accidental location of the epidural catheter in the subarachnoid space was observed in each group . As the CSE device , the P needles were more sophisticatedly design ed for easier insertion to the subarachnoid space than the H needles Background and Objectives Epidural injection has been known to enhance spinal anesthesia in combined spinal and epidural ( CSE ) anesthesia . Saline and local anesthetics have been reported to have a volume effect , elevating sensory level when supplementing a volume into the epidural space . We evaluated the effects of epidural injection when using the CSE technique for cesarean delivery . Methods Sixty-six parturients were allocated r and omly into group C ( control , n = 21 ) , S ( saline , n = 21 ) , or B ( bupivacaine , n = 24 ) : epidural injections of 10 mL saline and 0.25 % bupivacaine were given in groups S and B , respectively , 10 minutes after they received 8 mg of 0.5 % hyperbaric bupivacaine intrathecally , and no injection was given in group C. The sensory level at 10 minutes , the maximal level and the time to reach it , and degree of motor block and muscle relaxation were compared . We also investigated intraoperative side effects and postoperative findings in the postanesthesia care unit . Results Epidural injection raised the sensory level significantly in groups S and B , but the maximal height of sensory block and degree of muscle relaxation did not differ among the groups . Fewer patients complained of intraoperative pain in group B than in the other groups ( P < .001 ) . Conclusions We could not achieve satisfactory surgical analgesia with 8 mg of hyperbaric bupivacaine injected into the subarachnoid space using the needle-through-needle technique in cesarean deliveries . An epidural saline injection elevated the sensory level , which did not improve the spinal block , whereas an epidural injection of 10 mL of 0.25 % bupivacaine enhanced the spinal block and sustained the block postoperatively During placement of needles for combined spinal-epidural anesthesia ( CSEA ) , patients may experience pain , pressure , paresthesia , or discomfort during skin and deeper injection of local anesthetic , needle impingement on periosteum , dural puncture by the spinal needle , and insertion of the epidural catheter . We investigated the incidence of perception of and spontaneous verbal and motor responses to insertion of a spinal needle through the dura mater and pia mater and the effect of injecting lidocaine into the epidural space through the epidural needle before inserting the spinal needle through the meninges . Forty-three patients presenting for elective cesarean delivery under CSEA were studied . After localization of the epidural space using loss of resistance to air using a 17-gauge Tuohy needle , either 3 mL preservative free normal saline or 3 mL lidocaine 2 % plus epinephrine 1:200,000 was injected through the Tuohy needle . “ Needle through needle ” dural puncture was performed 1 min later using a 27-gauge Whitacre pencil-point needle . At the moment of dural puncture , 2 ( 9 % ) parturients given lidocaine and 17 ( 81 % ) parturients given saline ( P < 0.005 ) responded to dural puncture by spontaneously moving ( 33 % ) , spontaneously vocalizing ( 62 % ) , or , in response to direct question ing , by acknowledging ( 76 % ) having perceived sensation during thecal penetration . This study reveals that dural puncture by a Whitacre 27-gauge pencil-point needle inserted through a Tuohy epidural needle sited using loss of resistance to air causes involuntary movement , spontaneous vocalization , or is perceived by the majority of patients presenting for cesarean delivery under CSEA and that lidocaine injected into the epidural space before dural puncture largely eliminates these responses and sensations A group of 685 obstetric patients were r and omly allocated to have their epidural block performed using either a 16-gauge or an 18-gauge Tuohy needle . Bleeding was noted from needle or catheter trauma in 18 % of patients and it proved impossible to insert the catheter in 3 % . The majority of mothers experienced little discomfort during the procedure but 2 % found insertion to be very uncomfortable . There was no significant difference in the complication rate , ease of use , or patient discomfort between the 18- or 16-gauge needles . Epidural analgesia , although safe , is not without hazard . It may be difficult to perform and may , rarely , cause considerable discomfort It is generally believed that bolus injections of local anesthetic through an epidural needle produce a more rapid onset of blockade , but at the expense of an increased incidence and severity of hypotension , whereas intermittent injections through a catheter take longer to achieve adequate anesthesia but with a lower risk of hypotension . The present study investigated two commonly used needle and catheter epidural injection techniques for differences in speed of onset of surgical anesthesia and incidence and severity of hypotension . Term parturients scheduled for elective cesarean section were r and omized into two groups to receive epidural anesthesia with intermittent injection either through the epidural needle ( n = 44 ) or via a previously placed catheter ( n = 44 ) . The incidence and severity of hypotension was similar in the two groups . No significant difference was found for the time to onset of surgical anesthesia . In the absence of benefits of needle injection , incremental catheter administration of local anesthetic with its multiple safety advantages is the technique of choice for induction of epidural anesthesia for cesarean section Maternal position during induction of intrathecal anaesthesia for caesarean section influences block height and haemodynamic stability . In a r and omised study of 90 women presenting for elective caesarean section using combined spinal-epidural anaesthesia , three positions were compared -- the Oxford position ( group O ) , the right lateral to supine wedged ( group R ) and the sitting to supine wedged ( group S ) . Hyperbaric bupivacaine 12.5 mg with fentanyl 12.5 microg was injected intrathecally using a needle-through-needle CSE technique . Intravenous ephedrine 6 mg was given every minute that systolic blood pressure fell below 80 % of baseline . Time required for block height to reach T5 as assessed by light touch , was similar in the three groups . There were no significant differences in blood pressure although ephedrine requirements were less in group R. There were no significant differences in the incidence of maternal nausea and vomiting or in neonatal outcome as assessed by Apgar scores and umbilical cord blood gas analysis . Although the study failed to show any significant differences in block height between the groups , no women in group O had a block above T2 compared with three in group R and three in group Single , end-holed and multi-orifice extradural catheters were compared in terms of efficacy and complications when used for infusion of 0.1 % bupivacaine during labour . In this study of 364 patients there was no difference in unilateral block after an initial bolus dose ( 18 ( 11.5 % ) for single , end-holed and 16 ( 10.9 % ) for multi-orifice catheters ) . Unilateral block recurred with seven ( 4.0 % ) single , end-holed and with eight ( 4.8 % ) multi-orifice catheters . Unilateral blocks , arising for the first time during infusion of local anaesthetic , occurred significantly more frequently when single , end-holed catheters were used ( 29 ( 16.4 % ) ) compared with multi-orifice catheters ( 14 ( 8.4 % ) ) ( P < 0.05 ) An epidural injection of physiological saline solution after spinal anesthesia may produce a higher level of analgesia than spinal anesthesia alone because of a volume effect . The purpose of this study was to clarify the volume effect caused by epidural injection of saline after spinal anesthesia . Twenty patients undergoing combined spinal and epidural anesthesia for elective surgery whose analgesic levels did not reach the surgical regions 10 min after spinal anesthesia at the L4 - 5 interspace were r and omly assigned to two groups . The control group ( n = 10 ) received no epidural saline injection . The saline group ( n = 10 ) received 10 mL of saline through an epidural catheter at the L2 - 3 or L3 - 4 interspace 10 min after spinal anesthesia . In the saline group , the levels of analgesia 15 and 20 min after spinal anesthesia were significantly higher than those in the control group ( P < 0.05 ) . Next , we examined the volume effect of epidural injection of saline with myelography using two adult volunteers . In both volunteers , the upper level of the contrast medium , which was injected in the lumbar subarachnoid space , began to increase concurrently with lumbar epidural injection of saline , reaching from L3 to L1 and from L2 to T12 . The diameter of the subarachnoid space diminished to less than 25 % after injection of saline . We conclude that lumbar epidural injection of saline increases the analgesic level 10 min after spinal anesthesia , probably because of a volume effect . Implication s : In this study , using surgical patients and volunteers , we determined that a lumbar epidural injection of physiological saline solution 10 min after spinal anesthesia produces a higher analgesic level than spinal anesthesia alone because of a volume effect . ( Anesth Analg 1997;85:1097 - 100 STUDY OBJECTIVE To test the hypothesis that slow administration of local anesthetic into the epidural space by gravity flow reduces the incidence of signs and symptoms of unintended injection . DESIGN Prospect i ve , r and omized study . SETTING Teaching hospital . PATIENTS 600 ASA physical status l and II parturients scheduled for labor and delivery or elective cesarean section . INTERVENTIONS After identification of the epidural space with pulsations of an air-fluid column , parturients for vaginal delivery ( n = 380 ) were r and omized to receive a test dose of 3 ml 3 % 2-chloroprocaine with epinephrine 20 micrograms , two doses of 7 ml bupivacaine 0.03 % with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow ( Group 1 ) given over 30 seconds or by bolus injection ( Group 2 ) given over 5 seconds through the epidural needle ; parturients for Cesarean delivery ( n = 220 ) were r and omized to receive a test dose and two doses of 6 ml lidocaine 2 % with sufentanil 1 microgram/ml and epinephrine 2 micrograms/ml by either gravity flow or by bolus injection through the epidural needle . Changes in maternal heart rate ( HR ) and blood pressure , signs of intravascular injection , and adverse effects of epidural bupivacaine-sufentanil were recorded after each dose . MEASUREMENTS AND MAIN RESULTS Gravity flow administration ( Group 1 ) was associated with a smaller increase in mean maternal HR ( p < 0.001 ) , less hypotension ( p < 0.01 ) , sedation ( p < 0.01 ) , nausea ( p = 0.01 ) , and segmental spread ( p < 0.0001 ) than were corresponding doses given by traditional bolus injection ( Group 1 ) for vaginal or Cesarean deliveries . The incidence of systemic toxicity was zero of 300 ( 0 % ) with gravity flow and 4 of 300 ( 1.3 % ) by bolus injection , p = 0.12 , Fisher 's exact test . No patient in either group had an accidental intrathecal injection . CONCLUSION Gravity flow administration of local anesthetic-opioid solution during epidural block for obstetrics was associated with fewer signs of systemic drug absorption and cardiovascular perturbations than was the traditional bolus injection . This study supports the current opinion that slow administration of local anesthetic during epidural block contributes to fewer adverse events Increased attention has been directed at the quality of r and omized controlled trials ( RCTs ) and how they are being reported . We examined leading anesthesiology journals to identify if there were specific areas for improvement in the design and analysis of published clinical studies . All RCTs that appeared between January 2000 and December 2000 in leading anesthesiology journals ( Anesthesiology , Anesthesia & Analgesia , Anaesthesia , and Canadian Journal of Anaesthesia ) were retrieved by a MEDLINE search . We used a previously vali date d assessment tool , including 14 items associated with study quality , to determine a quality score for each article . The overall mean weighted quality score was 44 % ± 16 % . Overall average scores were relatively high for appropriate controls ( 77 % ± 7 % ) and discussion s of side effects ( 67 % ± 6 % ) . Scores were very low for r and omization blinding ( 5 % ± 2 % ) , blinding observers to results ( 1 % ± 1 % ) , and post-beta estimates ( 16 % ± 13 % ) . Important pretreatment clinical predictors were absent in 32 % of all studies . Significant improvement in the reporting and conduct of RCTs is required and should focus on r and omization methodology , the blinding of investigators , and sample size estimates . Repeat assessment s of the literature may improve the adoption of guidelines for the improvement of the quality of r and omized controlled trials Using continuous cardiotocography , the effect of maternal position on fetal heart rate ( FHR ) was studied during extradural analgesia ( EA ) with either 50 or 100 mg of etidocaine without adrenaline for labour and vaginal delivery . Of 70 healthy parturients , 39 were supine and 40 were in the lateral position . FHR was normal in all patients during the control period before EA , and remained normal during EA in 53 . Transient abnormal patterns occurred in 26 patients , 22 ( 56 % ) in the supine group and four ( 10 % ) in the lateral group , a significant difference ( P less than 0.001 ) . The decrease in arterial pressure ( AP ) did not differ between the groups , but the frequency of abnormal FHR associated with a small or moderate decrease in AP ( 30 % or less ) was greater in the supine ( 51 % ) than in the lateral group ( 3 % ) STUDY OBJECTIVE To investigate whether a change from a single-orifice to multi-orifice catheter could reduce the incidence of inadequate epidural blocks requiring replacement of the epidural catheter in obstetric patients . STUDY DESIGN Prospect i ve before-after cohort study . SETTING Obstetric unit at a university hospital . PATIENTS 872 patients requesting epidural analgesia for vaginal delivery or cesarean section . INTERVENTIONS Patients received epidural analgesia via single-orifice ( n = 433 ) or multi-orifice ( n = 439 ) epidural catheters , depending on the month of the trial . MEASUREMENTS AND MAIN RESULTS Patient characteristics , obstetric procedure , anesthesiologist characteristics , and details of epidural placement did not differ significantly between the groups . The overall replacement rate was 14.3 % in the single-orifice group versus 9.3 % in the multi-orifice group ( p = 0.032 ) . There were no difference in the frequency of replacement for subarachnoid placement or migration , immediate intravascular placement , vascular migration , or absence of any block . Significantly fewer catheters were replaced in the multi-orifice group for inadequate analgesia , defined as unblocked segments or unilateral block ( 6.4 % vs. 2.8 % , p = 0.018 ) . Paresthesias were less common in the multi-orifice group ( 22.4 % vs. 31.5 % , p = 0.003 ) . There were no unrecognized subarachnoid or vascular catheter placements in either group . CONCLUSIONS The multi-orifice design offers significant advantages over the single-orifice type for obstetricepidural analgesia Extradural anaesthesia was induced in 64 patients in either the sitting or the lateral position , for elective Caesarean section with either 0.5 % plain bupivacaine or 2 % lignocaine with adrenaline 1 in 200,000 . Onset was significantly shorter and a significantly greater number of patients were ready for surgery within 35 min following injection of lignocaine in the lateral position . Hypotension ( defined as a 25 % or greater reduction in arterial pressure ) occurred in 36 % of patients . Significantly more patients who had received the first injection of local anaesthetic agent in the sitting position required ephedrine to correct maternal hypotension . Most frequently , hypotension coincided with transfer of patients to theatre and thus was associated with movement of the patient in the presence of extensive sympathetic block Background and objective : Epidural vein cannulation has long been recognized as a problem in parturients due to distension of epidural veins . Epidural vein engorgement is maximal when the pregnant woman is in the supine position and minimal in the lateral position . Following an initial observation of an apparently high incidence of epidural vein cannulation in the sitting position , a r and omized trial was conducted to document whether such an association existed . Methods : A total of 209 term parturients were r and omized to either the sitting or lateral position ( 107 left lateral , 102 sitting ) . Epidural catheter placement was achieved using a loss of resistance to air technique with an 18‐G Tuohy needle . A data sheet was completed for each patient recording patient position , patient characteristics data , stage in labour and the incidence of epidural vein cannulation . Poor labour analgesia was defined as a visual analogue scale ( VAS ) > 40 mm on a 0‐100 mm pain intensity VAS . Results : The risk of epidural vein cannulation was significantly higher in the sitting group ( 16 of 102 = 15.7 % ) compared with the lateral position group ( 4 of 107 = 3.7 % ) , P = 0.011 . There was a significant association between epidural vein cannulation and poor analgesia ( P = 0.006 ) . These two variables remained independently significant on multiple regression analysis ( position , P = 0.009 ; analgesia , P = 0.006 ) . Conclusions : We conclude that there is a direct correlation between the incidence of epidural vein cannulation and patient posture during epidural catheter insertion in parturients A r and omised , single-blind study was conducted on 802 parturient women who required epidural analgesia , to compare open-end ( single hole ) with closed-end ( three lateral holes ) epidural catheters . The complication rate after catheter insertion was not statistically different between the two groups , but the number of unsatisfactory blocks was significantly higher in the open-end group ( p less than 0.001 ) . The closed-end catheters were easier and less painful to place , but gave a higher incidence of bloody taps . The open-end catheters caused sensory blockade to be more frequently unilateral and more frequently missed sensory segments . This result ed in a significantly higher number of open-end catheters that required replacement ( p less than 0.001 ) . Open-end catheters despite their theoretical advantages in the detection of intravenous and subarachnoid placement caused an unacceptably high incidence of unsatisfactory sensory blockade OBJECTIVES To determine the relationship between the quality of articles and whether they were published in a supplement or in the parent journal . DATA SOURCES AND STUDY SELECTION All r and omized control trials of drug therapies in adults published in the American Journal of Cardiology , the American Journal of Medicine and the American Heart Journal from January 1990 and obtained in November 1992 by means of a MEDLINE search . A total of 318 abstract s appeared to meet our inclusion criteria , and these articles were obtained and review ed in further detail . An additional 76 were excluded . DATA EXTRACTION Three review ers who were " blinded " and thus unaware of supplement status independently assessed the quality of each of the remaining 242 articles according to a st and ard quality scoring system . DATA SYNTHESIS Overall , 67 ( 27.7 % ) of the articles were published in journal supplements . Article quality scores ranged from 4.2 % to 87.5 % , with a mean ( + /- SD ) score of 37.2 % + /- 13.1 % . Quality scores were lower in articles published in journal supplements than in those published in the parent journal ( t[240 ] = 2.61 , P = .01 ) . The mean quality score for articles published in journal supplements was 33.6 % + /- 12.8 % compared with a score of 38.5 % + /- 13.1 % for articles published in the parent journal . Supplement articles included in their final analysis a smaller proportion of the patients initially r and omized ( t[75 ] = 2.8 , P = .007 ) . CONCLUSION Our findings suggest that r and omized control trials published in journal supplements are generally of inferior quality compared with articles published in the parent journal . The review process surrounding the publication of journal supplements should be consistent with that of the parent journal Adverse events associated with single-holed and multi-holed extradural catheters were compared in obstetric practice . Two hundred and forty-five patients were given an extradural block using a single-holed catheter and 229 received a block via a multi-holed catheter . There was no difference in the incidence of major side effects . Flow of fluid under gravity in the catheter was restricted significantly more often in the single-holed catheters . Blood was found significantly more often in the multi-holed catheters OBJECTIVE This study was design ed to determine the relationship between maternal position and the incidence of prolonged decelerations after epidural bupivacaine or intrathecal sufentanil analgesia for labor . STUDY DESIGN Laboring , healthy , term parturient women , with reassuring fetal heart rate tracings , requesting either epidural ( n = 145 ) or intrathecal ( n = 160 ) analgesia were r and omly assigned to lie either supine with measured 30-degree left uterine displacement ( n = 136 ) or in the left lateral decubitus position ( n = 145 ) . Patients received either intrathecal sufentanil , 10 microg , or epidural 0.25 % bupivacaine , 13 mL. An obstetrician , unaware of patient position or type of anesthesia , examined the fetal heart rate tracings . RESULTS No demographic differences were noted among the groups . Prolonged decelerations occurred with equal frequency after epidural bupivacaine and intrathecal sufentanil ( 3.9 % ) . Prolonged decelerations were not related to maternal position . No emergency cesarean deliveries were performed as a result of prolonged decelerations . Prolonged decelerations correlated with the frequency of contractions before induction of analgesia ( P < .05 ) . Fewer fetal heart rate accelerations were noted after intrathecal sufentanil than after epidural bupivacaine ( P < .005 ) . More ephedrine was used after epidural bupivacaine ( P < .001 ) . Patients who received epidural analgesia in the left lateral position were more likely to have an asymmetric block ( P < .05 ) . CONCLUSIONS The risk of prolonged deceleration after epidural bupivacaine or intrathecal sufentanil labor analgesia is unrelated to maternal position or analgesic technique The relative incidence of technical difficulties associated with multiport ( three lateral ports ) and uniport ( single distal port ) epidural catheters remains controversial . As part of a continuing institutional evaluation of epidural catheter insertion , 500 parturients were r and omized to have either a multiport or a uniport epidural catheter inserted 6 cm into the epidural space . Multiport epidural catheters were associated with inadequate analgesia less often and required manipulation less often than uniport epidural catheters . The incidences of intravenous cannulation , subsequent catheter dislodgement , and catheter replacement were similar for each catheter type . No multiport epidural catheter was associated with multicompartment placement . We conclude that multiport epidural catheters are preferable for use in laboring patients since they reduce the incidence of inadequate epidural analgesia . ( Anesth Analg 1997;84:1276 - 9 Purpose The loss-of-resistance technique is generally used to identify the epidural space usually with normal saline . However , the effect of epidural saline on anaesthetic spread has not been demonstrated . The purpose of this study was to determine whether epidural saline affected the anaesthetic level and the quality of analgesia . Methods Seventy patients undergoing upper abdominal surgery received thoracic epidural anaesthesia combined with general anaesthesia . The patients were r and omly allocated into three groups using epidural saline volumes of 1 , 5 , or 10 ml . Ten minutes after epidural injection of 12 ml mepivacaine 1 % , the dermatome levels of hypaesthesia for cold and pinprick were determined by an individual blinded to the amount of saline administered . Results The levels of hypaesthesia for cold sensation were not different among the three groups ( 23 [ 14–44 ] total bilateral dermatomes blocked with 1 ml saline , 22 [ 16–41 ] dermatomes with 5 ml , and 24 [ 10–36 ] dermatomes with 10 ml ( median [ range ] ) ) . However , the larger volume of saline produced decreased spread of hypaesthesia for pinprick ( 22 [ 4–41 ] dermatomes blocked bilaterally for 1 ml vs 16 [ 8–24 ] dermatomes for 10 ml group , P < 0.004 ) . Conclusion Our results suggest that a large volume of saline solution injected in the epidural space to elicit loss-of-resistance dilutes the local anaesthetic solution , result ing in reduced spread of the block to pinprick . RésuméObjectifLa technique de perte de résistance , utilisée surtout avec une solution physiologique salée , est généralement employée pour identifier l’espace péridural . Cependant , l’effet du soluté péridural sur l’extension anesthésique n’a pas été démontré . Le but de la présente étude était de déterminer si la solution péridurale a un effet sur le niveau et la qualité de l’anesthésie . MéthodeSoixante-dix patients devant subir une chirurgie abdominale basse ont reçu une anesthésie péridurale thoracique combinée à une anesthésie générale . Les patients ont été répartis de façon aléatoire en trois groupes , selon l’utilisation de solutions péridurales do nt les volumes étaient de 1 , 5 ou 10 ml . Dix minutes après l’injection péridurale de 12 ml de mépivacaïne 1 % , les niveaux d’hypesthésie au froid ( dermatome ) ou à la piqûre , ont été déterminés par un observateur qui ne connaissait pas le volume de solution administré . RésultatsLes niveaux d’hypesthésie à la sensation du froid n’ont pas été différents d’un groupe à l’autre ( 23 [ 14–44 ] dermatomes bilatéraux bloqués avec 1 ml de solution , 22 [ 16–41 ] dermatomes avec 5 ml et 24[10–36 ] dermatomes avec 10 ml ( [ intervalle ] médian ) ) . Toutefois , le plus gr and volume de solution a produit une plus faible extension de l’hypesthésie à la piqûre ( 22 [ 4–41 ] dermatomes bloqués bilatéralement avec 1 mlvs 16[8–24 ] dermatomes avec 10 ml , P < 0,004 ) . Conclusion Nos résultats suggèrent qu’un gr and volume de solution salée injecté dans l’espace péridural , pour permettre d’utiliser la technique de perte de résistance , dilue la solution anesthésique locale , ce qui résulte en une extension réduite du blocage de la sensibilité à la piqûre STUDY OBJECTIVE To determine whether threading an epidural catheter 10 cm then retracting it 5 cm affects its intravascular placement and paresthesias . DESIGN Prospect i ve r and omized study . SETTING Labor and Delivery Unit , University Medical Center . PATIENTS Eighty parturients . INTERVENTIONS All patients received epidural anesthesia . Patients were r and omized to 1 of 2 groups : threading the epidural catheter 5 cm ( 5-cm group ) or threading the epidural catheter 10 cm and retracting 5 cm ( 10-cm group ) . In the 10-cm group , the epidural catheter was threaded 10 cm and pulled back 5 cm . In the 5-cm group , the epidural catheter was threaded 5 cm . MEASUREMENTS AND MAIN RESULTS Placement of the epidural catheter intravascularly , the presence of a paresthesia , and bilateral sensory levels were measured . There was no difference in the frequency of intravascular placement between 10- and 5-cm groups , 10.2 % vs 7.5 % , respectively . Although not statistically significant , there was a trend toward a higher frequency of paresthesia in the 10-cm group , 15.4 % vs 7.5 % , and a lower frequency of uneven sensory levels in the 10-cm group , 15 % vs 2.6 % . CONCLUSIONS There is no clear clinical benefit or disadvantage to threading an epidural catheter 10 cm into the epidural space then withdrawing it 5 cm . Further study is warranted The catheter straight advancement rate for introduction into the epidural space was investigated using a radiopaque catheter . One hundred patients were divided into two groups and underwent thoracic or lumbar epidural punctures , with one of two different puncture methods : the median approach or paramedian approach . Two different angles of epidural puncture needle insertion , 50 - 60 degrees and 90 degrees to skin surface plane , were used . A catheter was inserted into the epidural space about 5 cm cephalad and the course of the inserted catheter was ascertained by radiography . The results have shown that punctures performed at an insertion angle of 50 - 60 degrees yielded higher catheter straight advancement rates than those performed at an angle of 90 degrees in both thoracic and lumbar epidural punctures The effect of maternal position in the period immediately following epidural administration on analgesia and side effects was examined during labour . Patients were r and omly allocated to two groups and were either turned from left to right lateral position within 5 minutes of bupivacaine administration ( n = 35 ) , or kept in the supine position , modified as appropriate , until pain relief or side effects indicated a change ( n = 35 ) . There was no significant difference between the two groups in onset or duration of analgesia , the need for supplements or in absorption of bupivacaine . Circulatory disturbances , all mild and transient , were seen in 14 patients ( eight lateral , six supine ) . There was no significant difference between the two groups either in the frequency of hypotension ( four lateral , five supine ) or of fetal heart deterioration ( four lateral , three supine ) . However motor block occurred in 15 of the lateral group and five supine ( p less than 0.02 ) . Such differences are not thought sufficient to counterbalance the potential circulatory disadvantage of the supine position In the present study we evaluated whether the sitting position during initiation of small-dose combined spinal-epidural anesthesia ( CSE ) would induce less hypotension as compared with the lateral position . Sixty women undergoing elective cesarean delivery were r and omly assigned to receive a spinal injection consisting of 6.6 mg hyperbaric bupivacaine with sufentanil 3.3 & mgr;g in either the lateral or the sitting position . After securing the epidural catheter , patients were turned to a 15 ° left lateral supine position . Ephedrine 5 mg IV was administered prophylactically and subsequently in case of nausea/vomiting and /or hypotension , defined as a systolic blood pressure less than 95 mm Hg or a 25 % decrease from baseline values . Although the incidence of ephedrine supplementation was not different , females in the sitting group required less ephedrine ( P = 0.012 ) and there were fewer problems with identifying the epidural space ( P = 0.01 ) . However , more patients in this group required epidural supplementation ( 35 % versus 3 % ; P = 0.007 ) . In the lateral group , blocks extended more cephalad than with the sitting position ( P = 0.014 ) . Apgar scores did not differ , but umbilical artery pH values were significantly higher in patients of the sitting group ( 7.31 ± 0.04 versus 7.26 ± 0.03 ; P = 0.02 ) . We conclude that performing a CSE technique for cesarean delivery in the sitting position was technically easier and induced less severe hypotension |
12,172 | 27,623,692 | The very limited available data indicated that the addition of multiplex allergen testing [ ImmunoCAP ( ® ) Immuno Solid-phase Allergen Chip ( ISAC ) , Thermo Fisher Scientific/Phadia AB , Uppsala , Sweden ] to st and ard diagnostic work-up can change the clinicians ' views on the diagnosis , management and treatment of patients .
There was some indication that the use of ImmunoCAP ISAC testing may be useful to guide decisions on the discontinuation of restrictive diets , the content of allergen-specific immunotherapy ( SIT ) prescriptions , and whether or not patients should receive SIT .
There was some evidence that ImmunoCAP ISAC may be useful for discriminating allergens that are structurally similar and are recognised by the same IgE antibody ( cross-immunoreactive ) .
Detailed cost analyses suggested that multiplex allergen testing would have to result in a substantial reduction of the proportions of patients receiving single IgE testing and oral food challenge tests in order to be cost-saving in the short term . | BACKGROUND Allergy is a form of immune-mediated exaggerated sensitivity ( hypersensitivity ) to a substance that is either inhaled , swallowed , injected or comes into contact with the skin .
Foreign substances that provoke allergies are called allergens .
It has been cl aim ed that multiplex allergen testing may help in diagnosing the cause of symptoms in patients with an unclear cause of allergy or who are allergic to more than one substance .
OBJECTIVES To evaluate multiplex allergen testing [ devices that can measure the presence of multiple immunoglobulin E ( IgE ) antibodies in a patient 's blood at the same time ] , by assessing ( 1 ) clinical effectiveness ( allergy symptoms , incidence of acute exacerbations , mortality , adverse events of testing and treatment , health-care presentations or admissions , health-related quality of life ) ; ( 2 ) effects on treatment ( diet , immunotherapy medications , other potential testing ) ; ( 3 ) any additional diagnostic information provided by multiplex allergen testing ; and ( 4 ) cost-effectiveness ( cost of different assessment strategies ) .
The clinical effectiveness and cost-effectiveness of the proposed protocol should then be assessed by comparing long-term clinical and quality of life outcomes and re source use in patients managed using the protocol with those managed using a st and ard diagnostic pathway . | Background Allergy test results can differ based on the method used . The most common tests include skin-prick testing ( SPT ) and in vitro tests to detect allergen-specific IgE. This study was design ed to assess allergy test results using SPT , individual specific IgE tests , and a multiallergen IgE assay ( multiple allergen simultaneous test ) in patients with chronic rhinitis and controls . Methods One hundred forty total patients were prospect ively enrolled in the study , including 100 patients with chronic rhinitis and 40 control patients without atopy . All eligible patients underwent SPT , serum analysis using individual specific IgE test , and multiple allergen simultaneous test against 10 common allergens . Allergy test results were then compared to identify correlation and interest agreement . Results There was an 81–97 % agreement between SPT and individual specific IgE test in allergen detection and an 80–98 % agreement between SPT and multiple allergen simultaneous test . Individual specific IgE test and multiple allergen simultaneous test allergy detection prevalence was generally similar to SPT in patients with chronic rhinitis . All control patients had negative SPT ( 0/40 ) , but low positive results were found with both individual specific IgE test ( 5–12.5 % ) and multiple allergen simultaneous test ( 2.5–7.5 % ) to some allergens , especially cockroach , Dermatophagoides farina , and ragweed . Agreement and correlation between individual specific IgE test and multiple allergen simultaneous test were good to excellent for a majority of tested allergens . Conclusion This study shows good agreement and correlation between SPT with individual specific IgE test and multiple allergen simultaneous test on a majority of the tested allergens for patients with chronic rhinitis . Comparing the two in vitro tests , individual specific IgE test agrees with SPT better than multiple allergen simultaneous test Background Grass allergen immunotherapy ( AIT ) reduces symptom severity in seasonal allergic rhinoconjunctivitis ( ARC ) but its impact on general health-related utility has not been characterised for the purpose s of economic evaluation . The aim of this study was to model the preferred measure of utility , EQ-5D index , from symptom severity and estimate incremental quality adjusted life years ( QALYs ) associated with SQ-st and ardised grass immunotherapy tablet ( GRAZAX ® , 75,000 SQ-T/2,800 BAU , ALK , Denmark ) . Methods Data were analysed from five consecutive pollen seasons in a r and omised placebo controlled trial of GRAZAX ® . Binomial and Gaussian mixed effects modelling related weekly EQ-5D index score to daily symptom and medication scores ( DSS & DMS respectively ) . In turn , daily EQ-5D index was estimated from ARC symptoms and medication use . Results DSS and DMS were the principal predictors of ‘ perfect ’ health ( EQ-5D = 1.000 ; binomial ) and ‘ imperfect ’ health ( EQ-5D < 1.000 ; Gaussian ) . Each unit increase in DSS and DMS reduced the odds of ‘ perfect ’ health ( EQ-5D = 1.000 ) by 27 % and 16 % respectively , and reduced ‘ imperfect ’ health by 0.17 and 0.13 , respectively . Gender remained the only other significant main fixed effect ( Male odds ratio [ OR ] = 1.82 ) . Incremental estimated EQ-5D index utility for GRAZAX ® was observed from day -30 to day + 70 of the pooled pollen season ; mean daily utility for GRAZAX ® = 0.938 units ( 95%CI 0.932 - 0.943 ) vs. 0.914 ( 0.907 - 0.921 ) for placebo , an incremental difference of 0.0238 ( p < 0.001 ) . This translates into an incremental 0.0324 Quality Adjusted Life Years over the five year study period . Conclusions ARC symptoms and medication use are the main predictors of EQ-5D index . The incremental QALYs observed for GRAZAX ® may not fully describe the health benefits of this treatment , suggesting that economic modelling may be conservative 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 The sensitisation profile at molecular level in plant-food allergy is complex . Several allergens may be involved , with different potential for severe reactions . lipid transfer proteins ( LTP ) are considered the most relevant plant-food allergens in adults in Mediterranean countries , but less is known in children . AIM To describe the clinical pattern and sensitisation profile of children with plant-food allergy and LTP sensitisation from Northeast Spain . METHODS Children with history of immediate reaction to plant-food(s ) , positive skin-prick-test to the culprit plant-food(s ) and specific-IgE to plant-food LTPs were analysed . RESULTS 130 children were included . 69.2 % ( 90/130 ) had reacted to ≥2 taxonomically unrelated plant-foods . Peach , walnut , hazelnut and peanut were most frequently involved . Reactions severity ranged from anaphylaxis ( 45.4 % , 59/130 ) to oral symptoms only . Sensitisation to a particular plant-food LTP not always caused clinical symptoms with that plant-food ; 69 % ( 40/58 ) and 63 % ( 17/27 ) of peach- and walnut-tolerant subjects had positive rPru p 3 and nJug r 3 specific IgE , respectively . 65.4 % ( 85/130 ) of children were also sensitised to storage proteins , which was associated to anaphylaxis and nut allergy . However , 60 % of patients without nuts/seeds allergy were sensitised to storage proteins . Specific-IgE levels to LTPs and /or storage proteins were not useful to predict allergy ( vs. tolerance ) to peach , walnut , peanut or hazelnut . CONCLUSIONS Sensitisation to LTP and /or storage proteins without clear clinical significance is relatively common . Prospect i ve longitudinal studies are required to evaluate the relevance of these silent sensitisations over time . Caution is required when interpreting the results of molecular-based diagnostic tools in clinical practice Background One fourth of the adult population in Europe suffer from respiratory allergy . Subcutaneous-allergen-specific-immunotherapy ( SCIT ) has long-term disease modifying effect on disease specific Health-Related Quality of Life ( HRQoL ) . The purpose of this study was to assess the effect of SCIT on alternative disease outcomes in patients with grass-pollen and /or house dust mite induced allergic rhino-conjunctivitis and /or an asthma diagnosis . Focus was on expressing outcomes in terms of generic quality of life ( Quality -Adjusted-Life-Years ( QALY ) ) and reductions in sick days . Methods The study was a multi-centre study with prospect i ve follow-up . 248 patients were initiated on SCIT . The disease specific Rhino-conjunctivitis Quality of Life Question naire ( RQLQ ) and two generic ( HRQoL ) instruments 15D and EQ-5D were used at baseline and at follow-up . The outcome measures included change in ; disease severity , RQLQ-scores , number of days with symptoms- and number of sick days per year and finally changes in generic HRQoL and thus , QALY . Disease severity was assessed by specialist doctors ; severity of rhino-conjunctivitis was classified according to the Allergic Rhinitis and its Impact on Asthma ( ARIA ) and asthma severity according to the Global Initiative for Asthma ( GINA guideline ) . The remaining outcome measures were assessed by the patients in question naires at baseline and at follow-up . An intension to treat approach was applied . For missing items imputation of sample mean base-line values or follow-up values were used after specified criteria . The effect of SCIT on rhino-conjunctivitis and /or asthma diagnoses was analysed at follow-up using three logistic regression models . Results The disease severity showed significantly improved disease control . Mean RQLQ-score was reduced from 3.02 at baseline to 2.00 at follow-up . Average annual days with symptoms were reduced from 189 to 145 days whilst annual sick days were reduced from 3.7 to 1.2 days . The 15D-score increased from 0.83 to 0.86 and the EQ-5D-score from 0.70 to 0.77 , which indicated an annual gain per patient of 0.03 - 0.06 QALY . Conclusions Allergic patients suffering from rhino-conjunctivitis alone or rhino-conjunctivitis and asthma experience significantly increased HRQoL and they gain 0.03 - 0.06 QALY , when treated with SCIT for one year . Trial registration The study was registered at Clinical Trials.gov with the identifier : NCT01486498 BACKGROUND Allergic rhinoconjunctivitis is a global health problem . Around 14 million people in Spain , France , Italy , and Austria suffer from grass pollen induced allergic rhinitis . St and ard care only provides symptoms relief , while allergen specific immunotherapy ( SIT ) treats the underlying cause of the disease . Grazax from ALK-Abelló is a new , tablet-based , effective route of SIT for home treatment . The objective was to assess the cost-effectiveness of Grazax in four Southern European countries . METHODS A prospect i ve pharmacoeconomic analyses was carried out alongside a multinational , clinical trial measuring the efficacy of Grazax . Pooled data on re source use and health outcomes were collected . A societal perspective was adopted , and the analysis had a nine-year time horizon . The primary outcome measure was quality adjusted life years ( QALYs ) . RESULTS Grazax was superior to st and ard care for all efficacy endpoints , including QALYs gained , and result ed in significantly less use of rescue medication and fewer hours missed from work . Grazax was cost-effective for all countries for an annual price in the range of 1500 euros - 1900 euros . The result was improved by inclusion of future costs of asthma and exclusion of Spanish trial centers which experienced an exceptionally low pollen season . CONCLUSION The analysis illustrates that allergen SIT with Grazax for grass pollen induced rhinoconjunctivitis is a cost-effective intervention in Southern Europe The objective of this study was to develop and test a health‐related quality of life question naire for clinical trials in rhinoconjunctivitis . The Rhinoconjunctivitis Quality of Life Question naire ( RQLQ ) was developed by asking patients to identify areas of their lives affected by rhinoconjunctivitis . The result ant RQLQ was tested for reproducibility , responsiveness and validity in a r and omized , double‐blind trial of regular versus ‘ as required ’ aqueous beclomethasone dipropionate ( BDP ) nasal spray in ragweed pollen‐induced rhinoconjunctivitis . Eighty‐five patients from previous rhinoconjunctivitis studies participated in the developmental survey . Sixty ragweed‐sensitive patients , from previous trials and media notices , were enrolled in the clinical trial . Aqueous BDP ( 800 μg ) nasal spray was administered regularly or ‘ as required ’ throughout the ragweed pollen season . The survey revealed that , in addition to local symptoms of rhinoconjunctivitis , patients experienced impairment of quality of life through systemic symptoms , sleep disturbance , practical problems , activity limitations and emotional problems . The RQLQ includes 28 questions related to these dimensions . Repeated administration of the RQLQ demonstrated good reproducibility . During the clinical trial , the RQLQ proved responsive in its ability to distinguish between regular and ‘ as required ’ medication use . Validity was shown by moderate to strong relations between changes in symptom diary scores and changes in RQLQ scores . In conclusion the RQLQ is likely to prove useful as a measure of health‐related quality of life in clinical trials in both rhinoconjunctivitis and rhinitis Background : Currently , the diagnosis of IgE‐mediated allergy is based on allergen‐specific history and diagnostic procedures using natural allergen extracts for in vivo and in vitro tests OBJECTIVES /HYPOTHESIS Health utility value ( HUV ) is an index used to measure health-related quality of life for the valuation and comparison of treatments . The Euroqol 5-Dimension ( EQ-5D ) question naire is a widely used method for determining HUV , but it has not been applied for this purpose in patients with chronic rhinosinusitis ( CRS ) who undergo sinus surgery . STUDY DESIGN Prospect i ve cohort study . METHODS Patients with CRS , who were recruited from 11 different otolaryngologic practice s , completed the EQ-5D question naire at baseline , as well as 3 , 12 , and 24 months after surgery . HUVs calculated from the results of this question naire were compared to those reported in the general U.S. population and to patients suffering from other chronic diseases . RESULTS Baseline EQ-5D surveys were completed by 242 patients . Mean baseline HUV ( st and ard deviation ) was 0.81 ( 0.13 ) . Female gender , revision surgery , and the use of intraoperative image guidance were associated was significantly lower baseline values . HUV rose at 3 months to 0.89 ( 0.12 ) and remained improved at 12 months 0.88 ( 0.10 ) and 24 months 0.89 ( 0.10 ) ( P < 0.001 ) . Baseline HUV in CRS ( 0.81[0.13 ] ) is lower than the general U.S. population ( 0.85 [ 0.18 ] ) and appears appropriately positioned among other common chronic conditions including asthma ( 0.82 - 0.92 ) , migraine ( 0.81 - 0.91 ) , and seasonal allergies ( 0.94 ) . CONCLUSIONS Sinus surgery provides improvement in HUV in patients with CRS . These values may be paired with costs of care to perform cost-utility analysis on this group of patients . LEVEL OF EVIDENCE 2c OBJECTIVES To evaluate the performances of an allergen microarray in multi-sensitized allergic patients with respiratory symptoms . DESIGN AND METHODS 321 patients and 92 controls were included in this study . Specific serum IgE were assayed using ImmunoCAP ISAC , a microarray containing 103 components derived from 47 allergens and results were compared with extract-based ImmunoCAP Allergens sIgE to 15 common airborne allergens . RESULTS The reproducibility of ISAC was good . The Positive Percent Agreement ( PPA ) varied between 75 % and 100 % for sIgE levels above 1 kUA/l . For sample s with sIgE levels below 0.1 kUA/l , the Negative Percent Agreement ( NPA ) ranged between 90 % and 100 % . Notably , 58 % of respiratory allergy patients had IgE to food-specific proteins and 52 % result ed sensitized to cross-reactive pan-allergens . CONCLUSION ImmunoCAP ISAC detects allergen sensitization at component level and adds important information by defining both cross and co-sensitization to a large variety of allergen molecules Background The incidence of anaphylaxis might be increasing . Data for fatal anaphylaxis are limited because of the rarity of this outcome . Objective We sought to document trends in anaphylaxis admissions and fatalities by age , sex , and cause in Engl and and Wales over a 20-year period . Methods We extracted data from national data bases that record hospital admissions and fatalities caused by anaphylaxis in Engl and and Wales ( 1992 - 2012 ) and crosschecked fatalities against a prospect i ve fatal anaphylaxis registry . We examined time trends and age distribution for fatal anaphylaxis caused by food , drugs , and insect stings . Results Hospital admissions from all-cause anaphylaxis increased by 615 % over the time period studied , but annual fatality rates remained stable at 0.047 cases ( 95 % CI , 0.042 - 0.052 cases ) per 100,000 population . Admission and fatality rates for drug- and insect sting – induced anaphylaxis were highest in the group aged 60 years and older . In contrast , admissions because of food-triggered anaphylaxis were most common in young people , with a marked peak in the incidence of fatal food reactions during the second and third decades of life . These findings are not explained by age-related differences in rates of hospitalization . Conclusions Hospitalizations for anaphylaxis increased between 1992 and 2012 , but the incidence of fatal anaphylaxis did not . This might be due to increasing awareness of the diagnosis , shifting patterns of behavior in patients and health care providers , or both . The age distribution of fatal anaphylaxis varies significantly according to the nature of the eliciting agent , which suggests a specific vulnerability to severe outcomes from food-induced allergic reactions in the second and third decades |
12,173 | 30,296,010 | Growth , vision , and hearing of ICSI and SC offspring also appear comparable , although important differences in general physical health , and particularly metabolic and reproductive health have been described , including recently poorer semen quality among ICSI-conceived young adult men compared to SC peers .
Whilst neurodevelopment , growth , vision , and hearing appear similar between ICSI and SC children , evidence suggests differences in general physical health , and metabolic and reproductive endpoints . | BACKGROUND A significant increase in the use of intracytoplasmic sperm injection ( ICSI ) since its introduction in 1992 has been observed worldwide , including beyond its original intended use for severe male factor infertility .
Concerns regarding ICSI include the effects of poor quality spermatozoa on offspring health and future fertility , and of the technique itself .
The health and development of ICSI-conceived children beyond early infancy have not been comprehensively assessed .
OBJECTIVE A systematic review of health outcomes of ICSI-conceived offspring beyond the neonatal period compared to spontaneously conceived ( SC ) offspring . | BACKGROUND As a continuation of two large-scale , multicentre studies on the development of 5-year-old ICSI children , we present results of the follow-up study undertaken on the cognitive and motor development of 8-year-old ICSI children . METHODS Developmental outcomes of 151 8-year-old singletons born through ICSI after 32 weeks of gestation were compared with those of 153 singletons of the same age born after spontaneous conception ( SC ) . Part of this population was seen in a cohort at the age 5 years . Outcome measures include Wechsler Intelligence Scale for Children-Revised ( WISC-R ) and Movement Assessment Battery for Children ( ABC ) . RESULTS Regarding intellectual functioning , ICSI children tend to obtain significantly higher total ( P < 0.01 ) , verbal ( P < 0.01 ) and performance ( P < 0.05 ) intelligence scores than SC children , nevertheless remaining in similar ranges . These effects are small ( Cohen 's d < 0.50 ) . High maternal educational level stayed in the regression as a factor accounting for some of the variance in total IQ between the groups . In terms of motor development , no significant differences were found between ICSI and SC children regarding overall motor skills , manual , balance and ball skills . CONCLUSION In this follow-up study , ICSI and SC children show a comparable cognitive and motor development until the age of 8 years Long-term follow-up studies on the health of children born after assisted reproduction technologies are m and atory . Vision and hearing are the most important senses that continue to develop during childhood . There are few reports on vision and hearing in preschool children born after assisted conception . This prospect i ve controlled blinded follow-up study examined 276 term-born singleton intracytoplasmic injection ( ICSI ) children and 273 spontaneously conceived controls at a mean age of 5.5 years and performed detailed vision and hearing test and clinical ly examined eyes and ears . There was no significant difference between ICSI and control children regarding the occurrence of vision or hearing impairments . Unsurprisingly , children with abnormalities in otoscopy were more likely to have an abnormal hearing test compared with children without abnormalities . Only 8.5 % of ICSI parents and 25.4 % of control parents whose children showed an abnormal hearing test knew about the hearing problems of their child . In conclusion , there was no difference in the development of hearing and vision in ICSI children and spontaneously conceived controls . But only few parents knew about hearing problems of their child after undergoing routine screening examinations . Parental interviews would therefore not be sufficient in order to assess vision and hearing in follow-up studies Recent studies have given conflicting results regarding growth in children born following assisted reproductive treatments up to the age of 18years . It has been suggested that children conceived via IVF may be taller than naturally conceived children and that this may due to subtle epigenetic alteration of imprinted genes as a result of the IVF process . A prospect i ve match-controlled study was performed to investigate the growth of children born in the UK following st and ard IVF and intracytoplasmic sperm injection ( ICSI ) up to the age of 12years . The study assessed 143 IVF and 166 ICSI children with 173 matched naturally conceived controls . Primary end-points were height and weight at various time points : birth , 5years , 7 - 9years and 10 - 12years . In addition , head circumference was assessed at birth . No significant differences were observed regarding head circumference , height and weight between the three groups at any of the time points . In conclusion , this preliminary study provides reassuring information regarding the growth of IVF and ICSI children up to 12years . Further studies must continue to investigate the growth and other outcomes in assisted-conception children as they develop through puberty into early adulthood OBJECTIVE To study the health of children born after ICSI and of spontaneously conceived control children at the age of 4 - 6 years . DESIGN Prospect i ve , controlled , blinded study . SETTING Tertiary-care center . PATIENT(S ) Two hundred seventy-six term-born singletons conceived by ICSI and 273 matched spontaneously conceived singletons at the age of 5.5 years . INTERVENTION(S ) Detailed physical examination , interview of the parents , and collection of data from each child 's examination booklet . MAIN OUTCOME MEASURE(S ) Biometrical data ; current health status ; acute , chronic and childhood illnesses ; hospitalizations ; and surgeries . RESULT ( S ) Detailed physical examination did not reveal any relevant differences between ICSI and spontaneously conceived children . There were no relevant differences regarding the incidence of childhood illnesses , acute or chronic illnesses , accidents , and surgeries up to the age of 5.5 years . However , a history of undescended testicles was found significantly more often in boys born after ICSI ( 5.4 % vs. 0.7 % ) , with the consequence that they had significantly more urogenital surgery ( 19.2 % vs. 8.9 % ) . Significantly more ICSI children had been hospitalized ( 37.6 % vs. 27.2 % ) , although we did not find any specific reason for the increased hospitalization rate . CONCLUSION ( S ) Other than an increased risk of undescended testicles and therefore an increase in urogenital surgeries in ICSI boys , the physical health of ICSI children was comparable to that of spontaneously conceived children at the age of 5.5 years Background : There is accumulating evidence that in vitro conception in humans may be associated with adverse health outcomes later in life . It has been proposed that suboptimal early life conditions may ‘ program ' key endocrine systems . A disturbance of the hypothalamic-pituitary-adrenal ( HPA ) axis leading to alterations in cortisol secretion in the offspring may be such a mechanism . To date , no data on cortisol levels in children conceived by intracytoplasmic sperm injection ( ICSI ) are available in the literature . Methods : In this cross-sectional study , salivary cortisol known as a key regulator of metabolism was measured and results were compared between 201 pubertal ICSI children and 196 spontaneously conceived ( SC ) counterparts . Results : ICSI females had lower mean salivary cortisol levels ( 9.0 µg/l ; 95 % CI 8.1 - 9.9 ) than SC females ( 10.6 µg/l ; 95 % CI 9.7 - 11.5 ; p = 0.01 ) . This difference remained after adjusting for current characteristics , early life factors and maternal characteristics . In ICSI males , no difference in cortisol levels was found in comparison with the SC group . Conclusion : In our study , 14-year-old female but not male ICSI teenagers were found to have lower salivary cortisol concentrations in comparison with SC peers . However , before definite conclusions can be drawn , our results should be completed by longitudinal sampling The aim of this prospect i ve follow-up study of children born after intracytoplasmic sperm injection ( ICSI ) was to compile data on karyotypes , congenital malformations , growth parameters and developmental milestones in order to evaluate the safety of this new technique . The study design included karyotyping of the parents and their agreement to genetic counselling and prenatal diagnosis and it was based on a physical examination of the child at the Centre for Medical Genetics at the ages of 2 months , 1 year and at 2 years , where major and minor malformations and psychomotor evolution are recorded . Here we describe the first 57 children born from 40 ICSI pregnancies with epididymal spermatozoa ( group 1 ) , the first 50 children born from 34 ICSI pregnancies with testicular spermatozoa ( group 2 ) and the first 58 children born from 48 pregnancies after replacement of cryopreserved ICSI embryos ( group 3 ) . Parental karyotypes were obtained from only 72/246 ( 29 % ) parents and were all normal . Prenatal karyotypes were determined for a total of 70 sample s ( 40 % ) : 21 in group 1 , 15 in group 2 and 34 in group 3 . In this last group 2 abnormal 47,XXY karyotypes ( 5.8 % ) and no structural aberrations were found . This increase in de-novo sex-chromosomal aberrations has already been described with regard to the first 877 children born after ICSI carried out at our Centre and is probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself . Major malformations , defined as those causing functional impairment or requiring surgical correction , were observed in four children : two born after ICSI with epididymal spermatozoa , one after ICSI with testicular spermatozoa and one after ICSI and cryopreservation . No particular malformation was disproportionally frequent . In the follow-up examinations at 2 months ( 107/161 or 66.5 % ) and at 1 year ( 37/161 or 22.9 % ) , no additional anomalies were observed . Lost for follow-up rate at 2 months was 33.5 % . These observations on a limited number of children do not suggest a higher incidence of diseases linked to imprinting , nor do they suggest a higher incidence of congenital malformations . These observations are still limited in number and should be further completed by others and by collaborative efforts . In the meanwhile patients should be told about the available data before any treatment : there appears to be some risk of transmitted chromosomal aberrations , of de-novo , mainly sex-chromosomal aberrations and of transmitting fertility problems to the offspring . Patients should also be reassured that until now there seems to be no higher incidence of congenital malformations in children born after ICSI with epididymal or testicular spermatozoa or after replacement of ICSI embryos STUDY QUESTION Does ovarian hyperstimulation , the in vitro procedures required for in vitro fertilization (IVF)/ intracytoplasmic sperm injection or the combination of both , affect the neurological outcome of 4-year-old singletons ? SUMMARY ANSWER Ovarian hyperstimulation , the in vitro procedure and the combination of both , were not associated with the worse neurological outcome in 4-year-old singletons . WHAT IS KNOWN ALREADY Assisted reproduction techniques ( ARTs ) are not associated with neurological dysfunction during the first post-natal years ; however , effects on the long-term neurological outcome are still inconclusive . An increased time to pregnancy ( TTP , a proxy for the severity of subfertility ) has been associated with a less optimal neurological condition at age 2 . The present study focuses on the neurodevelopmental outcome of 4-year-old ART-offspring . STUDY DESIGN , SIZE , DURATION Longitudinal , prospect i ve follow-up study . PARTICIPANTS , SETTING , METHODS Four-year-old singletons born to subfertile parents ( subfertile group , n = 195 ) , including singletons born after controlled ovarian hyperstimulation IVF ( COH-IVF , n = 63 ) , modified natural cycle IVF ( MNC-IVF , n = 53 ) and natural conception ( Sub-NC , n = 79 ) . Data on underlying cause of subfertility and TTP were present . In addition , we assessed newly recruited 4-year-old singletons born to fertile parents after natural conception ( reference group , n = 98 ) . Neurological development was evaluated with the neurological examination according to Hempel , result ing in a neurological optimality score ( NOS ) , a fluency score and the occurrence of the clinical ly relevant form of minor neurological dysfunction ( complex MND ) . The primary outcome was the fluency score , as fluency of movements is easily reduced by subtle brain dysfunction . Data were analysed with univariable and multivariable regression analyses , in which special attention was paid to sex differences in the neurological outcome . MAIN RESULTS AND THE ROLE OF CHANCE The fluency score , NOS and the prevalence of complex MND were similar in COH-IVF , MNC-IVF and Sub-NC children . The neurological condition of children born to subfertile parents was similar to that of children of fertile parents and was independent of the underlying cause of subfertility . No statistically significant associations were found between TTP and the fluency score and NOS . However , a positive correlation was found between TTP and the prevalence of complex MND ( TTP in years , adjusted odds ratio [ OR ] [ 95 % confidence interval , CI ] : 1.207 [ 1.038 to 1.404 ] , P = 0.014 ) ; a correlation which could be attributed to girls , in whom an evident positive correlation was present ( adjusted OR [ 95 % CI ] : 1.542 [ 1.161 to 2.047 ] , P = 0.003 ) . A similar association was absent in boys . LIMITATIONS , REASONS FOR CAUTION The prospect i ve design of our study and small post-natal attrition rate ( 9.3 % ) reduced potential selection bias based on the child 's development or health . The assessors were blind to the mode of conception , except for the group of children born to fertile parents , which was newly recruited . The study lacks sufficient power to conclude firmly that increased TTP is associated with a higher prevalence of complex MND . WIDER IMPLICATION S OF THE FINDINGS Our study suggests that the severity of subfertility , rather than its simple presence or components of IVF treatment , affects the neurological outcome . Moreover , girls may be neurologically more vulnerable for the effect of severity of subfertility . The finding that the severity of subfertility may be the decisive factor rather than the presence of a history of subfertility per se corroborates previous reports . Our results can not be generalized to multiples , as we studied singletons only . STUDY FUNDING /COMPETING INTERESTS The study was financially supported by the University Medical Center Groningen , grant number : 754510 , the Junior Scientific Masterclass , the Postgraduate School Behavioural and Cognitive Neurosciences and the Cornelia Foundation , Groningen , The Netherl and s. The authors have no conflicts of interest to declare CONTEXT Concern has been raised for the health of the offspring conceived by assisted reproduction technologies . Basal reproductive hormones around 3 months of age reflect the pituitary-testicular axis , which is transiently active at this age . OBJECTIVES We tested the hypothesis that transmission of impaired testicular function from father to son could be detected at 3 months of age in boys conceived by intracytoplasmic sperm injection ( ICSI ) , which is predominantly used in the management of male infertility . DESIGN We conducted a longitudinal prospect i ve cohort study , including 125 boys conceived by ICSI , 124 boys conceived by in vitro fertilization ( IVF ) , and 933 naturally conceived ( NC ) boys . INTERVENTION Anthropometrical measurements were performed at birth and at 3 months of age ; 58 , 67 , and 64 % of ICSI , IVF , and NC boys , respectively , had a blood sample taken at 3 months . MAIN OUTCOME MEASURES We measured serum levels of LH , FSH , SHBG , inhibin B , testosterone , as well as penile length . RESULTS Serum testosterone levels were significantly lower in boys conceived by ICSI ( 2.4 nmol/liter ; 0.2 - 4.9 nmol/liter ) ( median ; 2.5th-97.5th percentiles ) compared with NC boys ( 3.3 nmol/liter ; 0.6 - 7.6 nmol/liter ; P < 0.001 ) , and the LH to testosterone ratio was increased ( 0.8 ; 0.2 - 7.9 vs. 0.5 ; 0.2 - 2.3 , respectively ; P = 0.001 ) . Boys conceived by IVF because of female infertility factors had a normal serum testosterone and LH to testosterone ratio compared with controls . Adjusted analyses for confounders did not alter the results . CONCLUSIONS Our results point toward a subtle impairment of Leydig cell function in boys conceived by ICSI , possibly inherited from their fathers . The clinical significance of our findings is uncertain . However , our findings should raise concern because ICSI is increasingly used to overcome male infertility STUDY QUESTION Is academic performance in adolescents aged 15–16 years and conceived after ART , measured as test scores in ninth grade , comparable to that for spontaneously conceived ( SC ) adolescents ? SUMMARY ANSWER ART singletons had a significantly lower mean test score in the adjusted analysis when compared with SC singletons , yet the differences were small and probably not of clinical relevance . WHAT IS KNOWN ALREADY Previous studies have shown similar intelligence quotient ( IQ ) levels in ART and SC children , but only a few have been on adolescents . Academic performance measured with st and ardized national tests has not previously been explored in a complete national cohort of adolescents conceived after ART . STUDY DESIGN , SIZE , DURATION A Danish national registry-based cohort including all 4766 ART adolescents ( n = 2836 singletons and n = 1930 twins ) born in 1995–1998 were compared with two SC control cohorts : a r and omly selected singleton population ( n = 5660 ) and all twins ( n = 7064 ) born from 1995 to 1998 in Denmark . Nine children who died during the follow-up period were excluded from the study . PARTICIPANTS / MATERIAL S , SETTING , METHODS Mean test scores on a 7-point-marking scale from −3 to 12 were compared , and adjustments were made for relevant reproductive and socio-demographic covariates including occupational and educational level of the parents . MAIN RESULTS AND THE ROLE OF CHANCE The crude mean test score was higher in both ART singletons and ART twins compared with SC adolescents . The crude mean differences were + 0.41 ( 95 % CI 0.30–0.53 ) and + 0.45 ( 95 % CI 0.28–0.62 ) between ART and SC singletons and between ART and SC twins , respectively . However , the adjusted mean overall test score was significantly lower for ART singletons compared with SC singletons ( adjusted mean difference −0.15 ( 95 % CI −0.29−(−0.02 ) ) ) . For comparison , the adjusted mean difference was + 2.05 ( 95 % CI 1.82–2.28 ) between the highest and the lowest parental educational level , suggesting that the effect of ART is weak compared with the conventional predictors . The adjusted analyses showed significantly lower mean test scores in mathematics and physics/chemistry for ART singletons compared with SC singletons . Comparing ART twins with SC twins yielded no difference in academic performance in the adjusted analyses . Similar crude and adjusted overall mean test scores were found when comparing ART singletons and ART twins . LIMITATIONS , REASONS FOR CAUTION Missing data on educational test scores occurred in 6.6 % of adolescents aged 15–16 years for the birth cohorts 1995–1997 , where all of the children according to their age should have passed the ninth grade exam at the time of data retrieval . As sensitivity analyses yielded no significant difference in the adjusted risk of having missing test scores between any of the groups , it is unlikely that this should bias our results . Adjustment for body mass index and smoking during pregnancy was not possible . WIDER IMPLICATION S OF THE FINDINGS As our results are based on national data , our findings can be applied to other population s. The findings of this paper suggest that a possible small negative effect of parental subfertility or ART treatment is counterbalanced by the higher educational level in the ART parents . STUDY FUNDING /COMPETING INTEREST(S ) The Danish Medical Association in Copenhagen ( KMS ) funded this study with a scholarship grant . None of the authors had any competing interests . TRIAL REGISTRATION NO . ( STATISTICS DENMARK ) 704676 OBJECTIVE To assess the neurodevelopmental health of children born after intracytoplasmatic sperm injection ( ICSI ) . DESIGN Prospect i ve controlled blinded study . SETTING Tertiary care center . PATIENT(S ) A total of 276 term-born singletons conceived by ICSI and 273 matched spontaneously conceived ( SC ) singletons at the age of 5.5 years . MAIN OUTCOME MEASURE(S ) Neuromotor development assessed by a detailed neurologic examination , including the st and ardized motor test MOT 4 - 6 , and emotional/behavioral development and intelligence assessed with the Kaufman- Assessment Battery for Children . RESULT ( S ) There were no significant differences between ICSI children and control children regarding the neurologic examination , motor skills , emotional/behavioral development , and intelligence . CONCLUSION ( S ) The ICSI children born at term develop normally , similar to SC children OBJECTIVE To assess the somatic , psychomotor , and intellectual development of children conceived through intracytoplasmic single sperm injection ( ICSI ) over the whole preschool period . DESIGN Prospect i ve , controlled , cohort study . SETTING Fertility clinic in Brussels , Belgium . PATIENT(S ) Sixty-six ICSI-conceived children prospect ively compared with 52 IVF-conceived and 59 spontaneously conceived children . All children were full-term singletons . INTERVENTION(S ) Home visits by a trained psychologist . St and ardized interviews . Assessment s using the revised Brunet-Lézine scale and the revised Wechsler preschool and primary scale of intelligence . MAIN OUTCOME MEASURE(S ) Physical growth and general health . Formal developmental and intellectual assessment s. RESULT ( S ) Children conceived by ICSI were healthy : no significant differences appeared in the incidence of combined congenital malformations ( 11.3 % ) , health problems ( 44.1 % ) , surgical interventions ( 18.6 % ) , and hospitalizations ( 6.8 % ) , nor for the developmental assessment s ( mean developmental quotient at 9 months : 93.9 ; at 18 months : 102.0 ) . For the intellectual assessment s , the between-group differences disappeared when adjusted for levels of parental education ( mean intelligence quotient at 3 years : 97.0 ; at 5 years : 103.3 ) . CONCLUSION ( S ) This pilot study shows that throughout the preschool period , ICSI-conceived children have psychomotor and intellectual development similar to that of IVF-conceived and spontaneously conceived children . These conclusions need to be confirmed by multicenter studies BACKGROUND Intracytoplasmic sperm injection ( ICSI ) was introduced as a new form of in-vitro fertilisation ( IVF ) in 1993 and is now accepted as the treatment of choice for severe male infertility in many centres around the world . However , there is little information about the long-term outcome of children conceived by ICSI . We aim ed to find out the medical and developmental outcome of children conceived by ICSI at age 1 year . METHODS In this prospect i ve study , we compared the medical and developmental outcome at 1 year of 89 children conceived by ICSI with 84 children conceived by routine IVF , and with 80 children conceived naturally . Formal developmental assessment was done with Bayley Scales of Infant Development ( 2nd edition ) from which a mental development index ( MDI ) was derived . FINDINGS There was no significant difference in the incidence of major congenital malformations or major health problems in the first year of life . However , the mean Bayley MDI was significantly lower for the children conceived by ICSI than for the children conceived by routine IVF or naturally ( 95.9 [ SD 10.7 ] , 101.8 [ 8.5 ] , and 102.5 [ 7.6 ] , respectively , p < 0.0001 ) . 15 ( 17 % ) of 89 children conceived by ICSI experienced mildly or significantly delayed development ( MDI < 85 ) at 1 year compared with two ( 2 % ) of the 84 children conceived by IVF and one ( 1 % ) of the 80 children conceived by natural conception ( p < 0.0001 ) . INTERPRETATION Although most children conceived by ICSI are healthy and develop normally , there is an increased risk of mild delays in development at 1 year when compared with children conceived by routine IVF or conceived naturally . These findings support the need for ongoing developmental follow-up of children conceived by ICSI to see whether they are at increased risk of intellectual impairment or learning difficulties at school age |
12,174 | 30,872,538 | Women have conflicting opinions about antibiotic use during pregnancy .
Antibiotic treatment for women having significant bacteriuria likely reduces the incidence of pyelonephritis and low birth weight , but we are uncertain about the magnitude of the effect and about the extent to which we can apply these results to asymptomatic population s and screening programmes . | OBJECTIVE To systematic ally review screening and treatment effectiveness , and patient preferences , to inform recommendations by the Canadian Task Force on Preventive Health Care on screening for asymptomatic bacteriuria in pregnancy . | The presence of group-B streptococci in the urine of pregnant women seems to be associated with preterm labour . Urine sample s from 4122 women at 27 - 31 weeks ' gestation were examined for bacteria . Group-B streptococci were found in the urine of 69 women . In a double-blind , controlled study these patients were given either penicillin ( 10(6 ) IU three times daily for 6 days ; 37 patients ) or placebo ( 32 patients ) . The rates of primary rupture of the membranes ( 11 % v 53 % ; p less than 0.001 ) and preterm labour ( 5.4 % v 38 % ; p less than 0.002 ) were significantly lower in the penicillin group than in the placebo group . These results suggest that treatment and follow-up to prevent recolonisation in pregnant women with group-B streptococci in the urine may reduce the frequency of preterm labour in these patients BACKGROUND Existing approaches for the screening and treatment of asymptomatic bacteriuria in pregnancy are based on trials that were done more than 30 years ago . In this study , we reassessed the consequences of treated and untreated asymptomatic bacteriuria in pregnancy . METHODS In this multicentre prospect i ve cohort study with an embedded r and omised controlled trial , we screened women ( aged ≥18 years ) at eight hospitals and five ultrasound centres in the Netherl and s with a singleton pregnancy between 16 and 22 weeks ' gestation for asymptomatic bacteriuria . Screening was done with a single dipslide and two culture media . Dipslides were judged positive when the colony concentration was at least 1 × 10(5 ) colony-forming units ( CFU ) per mL of a single microorganism or when two different colony types were present but one had a concentration of at least 1 × 10(5 ) CFU per mL. Asymptomatic bacteriuria-positive women were eligible to participate in the r and omised controlled trial comparing nitrofurantoin with placebo treatment . In this trial , participants were r and omly assigned 1:1 to receive either nitrofurantoin 100 mg or identical placebo tablets , and were instructed to self-administer these tablets twice daily for 5 consecutive days . R and omisation was done by a web-based application with a computer-generated list with r and om block sizes of two , four , or six participants rendered by an independent data manager . 1 week after the end of treatment , they provided us with a follow-up dipslide . Women , treating physicians , and research ers all remained unaware of the bacteriuria status and treatment allocation . Women who refused to participate in the r and omised controlled trial did not receive any antibiotics , but their outcomes were collected for analysis in the cohort study . We compared untreated and placebo-treated asymptomatic bacteriuria-positive women with asymptomatic bacteriuria-negative women and nitrofurantoin-treated asymptomatic bacteriuria-positive women . The primary endpoint was a composite of pyelonephritis with or without preterm birth at less than 34 weeks , analysed by intention to treat at 6 weeks post-partum . This trial is registered with the Dutch Trial Registry , number NTR3068 . FINDINGS Between Oct 11 , 2011 , and June 10 , 2013 , we enrolled 5621 women into our screening cohort , of whom 5132 were eligible for screening . After exclusions for contaminated dipslides and patients lost to follow-up , in our final cohort of 4283 women , 248 were asymptomatic bacteriuria positive , of whom 40 were r and omly assigned to nitrofurantoin and 45 to placebo for the r and omised controlled trial , whereas the other 163 asymptomatic bacteriuria-positive women were followed without treatment . The proportion of women with pyelonephritis , preterm birth , or both did not differ between untreated or placebo-treated asymptomatic bacteriuria-positive women and asymptomatic bacteriuria-negative women ( 6 [ 2·9 % ] of 208 vs 77 [ 1·9 % ] of 4035 ; adjusted odds ratio [ OR ] 1·5 , 95 % CI 0·6 - 3·5 ) nor between asymptomatic bacteriuria-positive women treated with nitrofurantoin versus those who were untreated or received placebo ( 1 [ 2·5 % ] of 40 vs 6 [ 2·9 % ] of 208 ; risk difference -0·4 , 95 % CI -3·6 to 9·4 ) . Untreated or placebo-treated asymptomatic bacteriuria-positive women developed pyelonephritis in five [ 2·4 % ] of 208 cases , compared with 24 [ 0·6 % ] of 4035 asymptomatic bacteriuria-negative women ( adjusted OR 3·9 , 95 % CI 1·4 - 11·4 ) . INTERPRETATION In women with an uncomplicated singleton pregnancy , asymptomatic bacteriuria is not associated with preterm birth . Asymptomatic bacteriuria showed a significant association with pyelonephritis , but the absolute risk of pyelonephritis in untreated asymptomatic bacteriuria is low . These findings question a routine screen-treat-policy for asymptomatic bacteriuria in pregnancy . FUNDING ZonMw ( the Netherl and s Organisation for Health Research and Development ) A screening programme for the detection of asymptomatic bacteriuria in patients attending an antenatal clinic is described . The results obtained from the use of urinary antiseptics in a controlled trial over a period of two years are presented . The number of patients developing clinical pyelonephritis , fetal maturity at delivery and birth weight were recorded for treatment and control groups and compared with the equivalent results obtained from the total population of patients seen at the clinic The first part consisted of a prospect i ve study dealing with a series of 170 pregnancies during which cyto-bacteriological examination of urine was carried out in the 3rd , 5th , 7th and 9th months of pregnancy . Whenever bacteriuria was found it was treated . Those women found to be infected in pregnancy were re-examined bacteriologically and radiologically after delivery . A control series consisted of 200 pregnant women whose urines were not examined in this way unless they had clinical signs . In the first series 39 out of 170 women had at least one positive cyto-bacteriological test . 56 out of 638 examinations were abnormal . 50 had asymptomatic bacteriuria . No patient had any sign of acute pyelonephritis . In the control series 16 of the women had at least one positive cyto-bacteriological test . In all 21 tests were carried out ( 18 before signs of cystitis developed and 3 before symptoms of acute pyelonephritis ) . Treating asymptomatic bacteriuria is worth while because it helps to lower the incidence of pyelonephritis . There did not seem to be any relationship between premature labour , fetal mortality and maternal urinary pathology . Tests carried out at two definite intervals in pregnancy would seem to be a sufficient screening for preventing pyelonephritis and would be acceptable from the cost angle Although asymptomatic bacteriuria during pregnancy is associated with an increased risk of developing pyelonephritis , the effectiveness of screening programs to reduce this risk is controversial . A sharp reduction in the annual incidence of pyelonephritis ( 1.8 % to 0.6 % , P < .001 ) occurred after the introduction of a program to screen and treat asymptomatic bacteriuria among pregnant women followed at a large teaching hospital . The data provide retrospective and prospect i ve evidence that screening and treatment programs for asymptomatic bacteriuria during pregnancy reduce the risk of pyelonephritis in a population with a moderate to high prevalence of bacteriuria The incidence of impaired renal concentrating ability in pregnant women with asymptomatic significant bacteriuria is significantly less than previously reported when osmolality readings are performed on every urine specimen obtained during the 24 hours ' deprivation of fluids . The concentrating defect is more considerable as pregnancy progresses . The lower the maximum urinary osmolality the more difficult is the treatment of the patient , and the higher the incidence of acute pyelonephritis Although it has been shown that bacteriuria of pregnancy can be eradicated by keeping patients on antibacterial agents throughout pregnancy [ 1 ] , this regimen of treatment would be unacceptable to most individuals , particularly when asymptomatic ; and there are many who would question the ethical justification for such prolonged antibacterial therapy in pregnancy . This paper presents the results of a study design ed to determine whether antibacterial therapy of limited duration would eradicate |
12,175 | 22,336,795 | The available data from several small trials show that in patients with chronic heart failure , conventional diuretics appear to reduce the risk of death and worsening heart failure compared to placebo .
Compared to active control , diuretics appear to improve exercise capacity | BACKGROUND Chronic heart failure is a major cause of morbidity and mortality worldwide .
Diuretics are regarded as the first-line treatment for patients with congestive heart failure since they provide symptomatic relief .
The effects of diuretics on disease progression and survival remain unclear . | Although the benefits of antihypertensive treatment in " young " elderly ( under 70 years ) hypertensive patients are well established , the value of treatment in older patients ( 70 - 84 years ) is less clear . The Swedish Trial in Old Patients with Hypertension ( STOP-Hypertension ) was a prospect i ve , r and omised , double-blind , intervention study set up to compare the effects of active antihypertensive therapy ( three beta-blockers and one diuretic ) and placebo on the frequency of fatal and non-fatal stroke and myocardial infa rct ion and other cardiovascular death in hypertensive Swedish men and women aged 70 - 84 years . We recruited 1627 patients at 116 health centres throughout Sweden , who were willing to participate , and who met the entry criteria of three separate recordings during a 1-month placebo run-in period of systolic blood pressure between 180 and 230 mm Hg with a diastolic pressure of at least 90 mm Hg , or a diastolic pressure between 105 and 120 mm Hg irrespective of the systolic pressure . The total duration of the study was 65 months and the average time in the study was 25 months . 812 patients were r and omly allocated active treatment and 815 placebo . The mean difference in supine blood pressure between the active treatment and placebo groups at the last follow-up before an endpoint , death , or study termination was 19.5/8.1 mm Hg . Compared with placebo , active treatment significantly reduced the number of primary endpoints ( 94 vs 58 ; p = 0.0031 ) and stroke morbidity and mortality ( 53 vs 29 ; p = 0.0081 ) . Although we did not set out to study an effect on total mortality , we also noted a significantly reduced number of deaths in the active treatment group ( 63 vs 36 ; p = 0.0079 ) . The benefits of treatment were discernible up to age 84 years . We conclude that antihypertensive treatment in hypertensive men and women aged 70 - 84 confers highly significant and clinical ly relevant reductions in cardiovascular morbidity and mortality as well as in total mortality Neuroendocrine activation is known to occur in patients with congestive heart failure , but there is uncertainty as to whether this occurs before or after the presence of overt symptoms . In the Studies of Left Ventricular Dysfunction ( SOLVD ) , a multicenter study of patients with ejection fractions of 35 % or less , we compared baseline plasma norepinephrine , plasma renin activity , plasma atrial natriuretic factor , and plasma arginine vasopressin in 56 control subjects , 151 patients with left ventricular dysfunction ( no overt heart failure ) , and 81 patients with overt heart failure before r and omization . Median values for plasma norepinephrine ( p = 0.0001 ) , plasma atrial natriuretic factor ( p less than 0.0001 ) , plasma arginine vasopressin ( p = 0.006 ) , and plasma renin activity ( p = 0.03 ) were significantly higher in patients with left ventricular dysfunction than in normal control subjects . Neuroendocrine values were highest in patients with overt heart failure . Plasma renin activity was normal in patients with left ventricular dysfunction without heart failure who were not receiving diuretics and was significantly increased ( p less than 0.05 ) in patients on diuretic therapy . We conclude that neuroendocrine activation occurs in patients with left ventricular dysfunction and no heart failure . Neuroendocrine activation is further increased as overt heart failure ensues and diuretics are added to therapy The diuretic and clinical efficacy and safety of piretanide , a new high‐ceiling loop diuretic , was determined in patients with mild to moderately severe congestive heart failure . Piretanide ( n = 20 ) administered orally in a daily dosage of up to 24 mg was compared with placebo ( n = 18 ) for 28 days , using a double‐blind , r and omized , parallel design . Patients were hospitalized during the first 5 days of the study when dosage titration was established and 24‐hour fractionated urine collection s were obtained . Piretanide caused significant diuresis for 3 hours after ingestion with a natriuretic response noted for up to 6 hours . While occasional kaliuretic response was noted , it did not significantly increase 24‐hour urinary potassium excretion . Only one patient treated with the highest allowed dose of piretanide developed mild hypokalemia . An improvement in New York Heart Association functional class status was noted after piretanide therapy . In contrast , patients who received placebo exhibited no significant improvement . BUN increased in nine piretanide‐treated patients ; two were discontinued from the study because of progressive azotemia . However , there was no significant increase in serum creatinine levels . Other blood , physical , ECG , and audiometrie examinations also revealed no significant abnormalities . The study suggests that oral piretanide is a relatively safe and effective diuretic for treating congestive heart failure with a potential advantage of having potassium‐sparing properties Background Ten chronic heart failure patients were studied on three occasions in r and omized double-blind fashion to compare the acute hemodynamic , neurohormonal , and renal sodium-h and ling responses to 1 mg captopril versus 25 mg captopril , both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis . Methods and Results Compared with placebo , 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination . Captopril ( 25 mg ) produced marked suppression of serum angiotensin II with or without oral furosemide ( both p < 0.002 ) , a marked decrease in mean arterial pressure ( p < 0.0001 ) that was accentuated by furosemide ( p < 0.00001 ) , and a decrease in glomerular filtration rate ( p = 0.0007 ) . No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide . In contrast , while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide , 1 mg captopril significantly enhanced furosemideinduced natriuresis ( p < 0.05 ) . No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session . This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens . Conclusions We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure , captopril at a starting dose of 1 mg ( but not 25 mg ) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration , while off setting the antinatriuretic renal tubular effects of angiotensin II BACKGROUND The RALES study showed that spironolactone , added to conventional therapy for chronic heart failure , dramatically reduced mortality . We tested the hypothesis that this benefit was partially due to improvement in endothelial function and /or to amplified suppression of the vascular renin-angiotensin axis . METHODS AND RESULTS We performed a r and omized , placebo-controlled , double-blind crossover study on 10 patients with NYHA class II to III chronic heart failure on st and ard diuretic/ACE inhibitor therapy , comparing 50 mg/d spironolactone ( 1 month ) versus placebo . Forearm vasculature endothelial function was assessed by bilateral forearm venous occlusion plethysmography using acetylcholine and N-monomethyl-L-arginine ( L-NMMA ) , with sodium nitroprusside as a control vasodilator . Also , vascular ACE activity was assessed by use of angiotensin ( Ang ) I , with Ang II as a control vasoconstrictor . Spironolactone significantly increased the forearm blood flow response to acetylcholine ( percentage change in forearm blood flow [ mean+/-SEM ] , 177+/-29 % versus 95+/-20 % , spironolactone versus placebo ; P<0.001 ) , with an associated increase in vasoconstriction due to L-NMMA ( -35+/-6 % versus -18+/-4 % ; P<0.05 ) . The Ang I response was also significantly reduced with spironolactone ( P<0.05 ) , with Ang II responses unaltered . CONCLUSIONS Spironolactone improves endothelial dysfunction , increases NO bioactivity , and inhibits vascular Ang I/Ang II conversion in patients with heart failure , providing novel mechanisms for its beneficial effect on cardiovascular mortality Background — In patients with chronic heart failure ( CHF ) , a β-blocker is generally added to a regimen containing an angiotensin-converting-enzyme ( ACE ) inhibitor . It is unknown whether β-blockade as initial therapy may be as useful . Methods and Results — We r and omized 1010 patients with mild to moderate CHF and left ventricular ejection fraction ≤35 % , who were not receiving ACE inhibitor , β-blocker , or angiotensin receptor blocker therapy , to open-label monotherapy with either bisoprolol ( target dose 10 mg QD ; n=505 ) or enalapril ( target dose 10 mg BID ; n=505 ) for 6 months , followed by their combination for 6 to 24 months . The 2 strategies were blindly compared with regard to the combined primary end point of all-cause mortality or hospitalization and with regard to each of these end point components individually . Bisoprolol-first treatment was noninferior to enalapril-first treatment if the upper limit of the 95 % confidence interval ( CI ) for the absolute between-group difference was < 5 % , corresponding to a hazard ratio ( HR ) of 1.17 . In the intention-to-treat sample , the primary end point occurred in 178 patients allocated to bisoprolol-first treatment versus 186 allocated to enalapril-first treatment ( absolute difference −1.6 % , 95 % CI −7.6 to 4.4 % , HR 0.94 ; 95 % CI 0.77 to 1.16 ) . In the per- protocol sample , 163 patients allocated to bisoprolol-first treatment had a primary end point , versus 165 allocated to enalapril-first treatment ( absolute difference −0.7 % , 95 % CI −6.6 to 5.1 % , HR 0.97 ; 95 % CI 0.78 to 1.21 ) . With bisoprolol-first treatment , 65 patients died , versus 73 with enalapril-first treatment ( HR 0.88 ; 95 % CI 0.63 to 1.22 ) , and 151 versus 157 patients were hospitalized ( HR 0.95 ; 95 % CI 0.76 to 1.19 ) . Conclusion — Although noninferiority of bisoprolol-first versus enalapril-first treatment was not proven in the per- protocol analysis , our results indicate that it may be as safe and efficacious to initiate treatment for CHF with bisoprolol as with enalapril AIMS It is reported that one third of patients with heart failure have normal left ventricular systolic function , and may or may not have left ventricular diastolic dysfunction . We sought to define the prevalence of left ventricular diastolic filling abnormalities in a large unselected group of patients , unlike the diagnosis by exclusion in the small highly selected groups of patients studied previously . METHODS AND RESULTS Patients were referred by general practitioners to an open-access echocardiography service for assessment of possible heart failure . Echocardiography included a Doppler study of transmitral flow at the tips of the mitral leaflets and calculation of an E/A ratio . Of 534 patients referred and assessed , 371 patients had normal systolic function and a measurable E/A ratio . These were compared with age-adjusted reference ranges to give 9 above the reference range and 19 below . This is only 10 more than would be expected if our patients were normal . In the same group of patients we found 96 cases of left ventricular systolic dysfunction , or 52 amongst the 423 with a measurable E/A ratio . CONCLUSION Either left ventricular diastolic filling abnormalities are very much less common than previously supposed or the E/A ratio is almost useless for their detection OBJECTIVES We sought to determine whether non-potassium-sparing diuretics ( PSDs ) in the absence of a PSD may result in progressive heart failure ( HF ) . BACKGROUND Angiotensin-converting enzyme ( ACE ) inhibitors incompletely suppress ACE activity in HF patients . Furthermore , non-PSDs are activators of aldosterone secretion . We reasoned that non-PSDs , in the absence of a PSD , might result in progressive HF . METHODS In the 6,797 patients in the Studies Of Left Ventricular Dysfunction ( SOLVD ) , we compared the risk of hospitalization for , or death from , HF between those taking a PSD and those who were not , adjusting for known covariates . RESULTS The risk of hospitalization from worsening HF in those taking a PSD relative to those taking only a non-PSD was 0.74 ( 95 % confidence interval [ CI ] 0.55 to 0.99 ; p = 0.047 ) . The relative risk for cardiovascular death was 0.74 ( 95 % CI 0.59 to 0.93 ; p = 0.011 ) , for death from all causes 0.73 ( 95 % CI 0.59 to 0.90 ; p = 0.004 ) , and for hospitalization for , or death from , HF 0.75 ( 95 % CI 0.58 to 0.97 ; p = 0.030 ) . Compared with patients not taking any diuretic , the risk of hospitalization or death due to worsening HF in patients taking non-PSDs alone was significantly increased ( risk ratio [ RR ] = 1.31 , 95 % CI 1.09 to 1.57 ; p = 0.0004 ) ; this was not observed in patients taking PSDs with or without a non-PSD ( RR = 0.99 , 95 % CI 0.76 to 1.30 ; p = 0.95 ) . CONCLUSIONS The use of PSDs in HF patients is associated with a reduced risk of death from , or hospitalization for , progressive HF or all-cause or cardiovascular death , compared with patients taking only a non-PSD BACKGROUND It is not known whether the treatment of patients with asymptomatic left ventricular dysfunction reduces mortality and morbidity . We studied the effect of an angiotensin-converting -- enzyme inhibitor , enalapril , on total mortality and mortality from cardiovascular causes , the development of heart failure , and hospitalization for heart failure among patients with ejection fractions of 0.35 or less who were not receiving drug treatment for heart failure . METHODS Patients were r and omly assigned to receive either placebo ( n = 2117 ) or enalapril ( n = 2111 ) at doses of 2.5 to 20 mg per day in a double-blind trial . Follow-up averaged 37.4 months . RESULTS There were 334 deaths in the placebo group , as compared with 313 in the enalapril group ( reduction in risk , 8 percent by the log-rank test ; 95 percent confidence interval , -8 percent [ an increase of 8 percent ] to 21 percent ; P = 0.30 ) . The reduction in mortality from cardiovascular causes was larger but was not statistically significant ( 298 deaths in the placebo group vs. 265 in the enalapril group ; risk reduction , 12 percent ; 95 percent confidence interval , -3 to 26 percent ; P = 0.12 ) . When we combined patients in whom heart failure developed and those who died , the total number of deaths and cases of heart failure was lower in the enalapril group than in the placebo group ( 630 vs. 818 ; risk reduction , 29 percent ; 95 percent confidence interval , 21 to 36 percent ; P less than 0.001 ) . In addition , fewer patients given enalapril died or were hospitalized for heart failure ( 434 in the enalapril group ; vs. 518 in the placebo group ; risk reduction , 20 percent ; 95 percent confidence interval , 9 to 30 percent ; P less than 0.001 ) . CONCLUSIONS The angiotensin-converting -- enzyme inhibitor enalapril significantly reduced the incidence of heart failure and the rate of related hospitalizations , as compared with the rates in the group given placebo , among patients with asymptomatic left ventricular dysfunction . There was also a trend toward fewer deaths due to cardiovascular causes among the patients who received enalapril BACKGROUND To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure , we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure . The patients were r and omly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily . The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial . RESULTS Mortality after two years was significantly lower in the enalapril arm ( 18 percent ) than in the hydralazine-isosorbide dinitrate arm ( 25 percent ) ( P = 0.016 ; reduction in mortality , 28.0 percent ) , and overall mortality tended to be lower ( P = 0.08 ) . The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death , and this beneficial effect was more prominent in patients with less severe symptoms ( New York Heart Association class I or II ) . In contrast , body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment ( P less than 0.05 ) , and left ventricular ejection fraction , which increased with both regimens during the 2 years after r and omization , increased more ( P less than 0.05 ) during the first 13 weeks in the hydralazine-isosorbide dinitrate group . CONCLUSIONS The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial ( 26 percent ) and in the present trial ( 25 percent ) , as compared with that in the placebo arm in the previous trial , ( 34 percent ) and the further survival benefit with enalapril in the present trial ( 18 percent ) strengthen the conclusion that vasodilator therapy should be included in the st and ard treatment for heart failure . The different effects of the two regimens ( enalapril and hydralazine-isosorbide dinitrate ) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in r and omised order . Four different methods were used to assess the patients ' response to treatment . Both treatments improved symptom-limited exercise tolerance , higher-dose frusemide having a more favourable effect . Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments . The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments ; again higher-dose frusemide had a more beneficial effect . The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea , fatigue , and general well-being Summary Potassium-sparing diuretics have been reported to decrease the positive inotropic effect of digoxin . We studied the hemodynamic effects of amiloride in patients taking digoxin for chronic heart failure . Eleven men with a history of congestive heart failure were studied in a double blind , cross-over , placebo controlled trial with the patients on digoxin alternating placebo with amiloride . After 7 days on the trial drug , a Swan-Ganz catheter was placed in the pulmonary artery and measurements made at rest and with increasing degrees of supine bicycle exercise . Right-sided and pulmonary artery wedge pressures and systemic arterial pressures , as well as cardiac outputs , were measured . After a 7 day washout period , placebo ( P ) and Amiloride ( A ) were switched and after 7 days on the therapy , a second hemodynamic study at rest and varying degrees of supine bicycle exercise was repeated . At rest there were no significant differences in the rightsided , pulmonary arterial wedge pressure or cardiac outputs between the patients on Amiloride ( A ) versus placebo ( P ) . During exercise there were significant differences between ( P ) and ( A ) at the 50 watt-second stage of exercise . Right atrial pressures ( P = 15.0 ± 6.8 mm Hg vs A = 10.5 ± 5.4 mm Hg ) , PA wedge pressure ( P = 28.6 ± 8.5 vs A = 22.1 ± 7.3 mm Hg ) , PA diastolic pressure ( P = 32.2 ± 9.9 mm Hg ) vs A = 21.6 ± 10.0 mm Hg ) , and mean PA pressure ( P = 44.4 ± 11.0 vs A = 38.9 ± 12.5 mm Hg ) , were all lower on ( A ) than on ( P ) and the left ventricular stroke work index ( LVSWI ) ( P = 69.5 ± 18.0 vs A = 77.9 ± 22.2 Gm-m/m2 ) , stroke volume index ( P = 44.9 ± 8.8 vs A = 46.2 ± 11.4 ) cc/beat/m2 were higher than on placebo . This study clearly demonstrates no decrease in the inotropic action of digoxin when A was added to a regimen of digoxin and diuretics combined , and may possibly improve ventricular performance compared to digoxin and diuretics alone . The mechanism by which the A improves the ventricular function and promptly increases the inotropic effect in patients taking digoxin is unclear . The addition of ( A ) to digoxin appears to be safe and may provide clinical benefit above and beyond potassium-sparing Abstract The Framingham study demonstrated that the 5-year mortality after the onset of symptoms of congestive heart failure ( CHF ) was 62 % for men and 42 % for women . 1 Franciosa et al 2 found that the 3-year mortality rate for men with chronic CHF due to coronary artery disease or idiopathic dilated cardiomyopathy was 76 % . CHF may occur with normal or abnormal left ventricular ( LV ) ejection fraction . 3–8 We report the results from a prospect i ve study of elderly patients with CHF associated with coronary artery disease correlating normal and abnormal LV ejection fraction with cardiac mortality and total mortality The non-sulfhydryl selective angiotensin-converting enzyme inhibitor benazepril ( 20 mg daily ) was compared with hydrochlorothiazide ( 50 mg daily ) in post-infa rct ion ( 6 - 24 months ) patients with symptomatic ( NYHA functional class 2 ) mild heart failure . No concomitant drug therapy was given . The study had a double-blind cross-over design with 3-month treatment periods . Both drugs were well tolerated , and both caused a similar reduction in systolic blood pressure . Heart rate was higher with the diuretic . Benazepril improved the NYHA functional class in 17 out of 29 ( 59 % ) patients , whereas one patient improved with hydrochlorothiazide ( P = 0.0004 ) . With regard to global efficacy score , benazepril was also superior . Thus , angiotensin-converting enzyme inhibitors may be superior to diuretics as first-choice therapy in symptomatic mild heart failure BACKGROUND Patients with congestive heart failure have a high mortality rate and are also hospitalized frequently . We studied the effect of an angiotensin-converting-enzyme inhibitor , enalapril , on mortality and hospitalization in patients with chronic heart failure and ejection fractions less than or equal to 0.35 . METHODS Patients receiving conventional treatment for heart failure were r and omly assigned to receive either placebo ( n = 1284 ) or enalapril ( n = 1285 ) at doses of 2.5 to 20 mg per day in a double-bind trial . Approximately 90 percent of the patients were in New York Heart Association functional classes II and III . The follow-up averaged 41.4 months . RESULTS There were 510 deaths in the placebo group ( 39.7 percent ) , as compared with 452 in the enalapril group ( 35.2 percent ) ( reduction in risk , 16 percent ; 95 percent confidence interval , 5 to 26 percent ; P = 0.0036 ) . Although reductions in mortality were observed in several categories of cardiac deaths , the largest reduction occurred among the deaths attributed to progressive heart failure ( 251 in the placebo group vs. 209 in the enalapril group ; reduction in risk , 22 percent ; 95 percent confidence interval , 6 to 35 percent ) . There was little apparent effect of treatment on deaths classified as due to arrhythmia without pump failure . Fewer patients died or were hospitalized for worsening heart failure ( 736 in the placebo group and 613 in the enalapril group ; risk reduction , 26 percent ; 95 percent confidence interval , 18 to 34 percent ; P less than 0.0001 ) . CONCLUSIONS The addition of enalapril to conventional therapy significantly reduced mortality and hospitalizations for heart failure in patients with chronic congestive heart failure and reduced ejection fractions Several small studies have suggested beneficial effects of long-term beta-blocker treatment in idiopathic dilated cardiomyopathy . Our large multicentre study aim ed to find out whether metoprolol improves overall survival and morbidity in this disorder . 383 subjects with heart failure from idiopathic dilated cardiomyopathy ( ejection fraction < 0.40 ) were r and omly assigned placebo or metoprolol . 94 % were in New York Heart Association functional classes II and III , and 80 % were receiving background treatment . A test dose of metoprolol ( 5 mg twice daily ) was given for 2 - 7 days ; those tolerating this dose ( 96 % ) entered r and omisation . Study medication was increased slowly from 10 mg to 100 - 150 mg daily . There were 34 % ( 95 % CI -6 to 62 % , p = 0.058 ) fewer primary endpoints in the metoprolol than the placebo group ; 2 and 19 patients , respectively , deteriorated to the point of needing transplantation and 23 and 19 died . The change in ejection fraction from baseline to 12 months was significantly greater with metoprolol than with placebo ( 0.13 vs 0.06 , p < 0.0001 ) . Pulmonary capillary wedge pressure decreased more from baseline to 12 months with metoprolol than with placebo ( 5 vs 2 mm Hg , p = 0.06 ) . Exercise time at 12 months was significantly greater ( p = 0.046 ) in metoprolol-treated than in placebo-treated patients . In patients with idiopathic dilated cardiomyopathy , treatment with metoprolol prevented clinical deterioration , improved symptoms and cardiac function , and was well tolerated |
12,176 | 18,843,753 | More intensive editorial processes were associated with fewer errors in abstract s and references .
Structuring generally improved the quality of abstract s , but increased their length .
Surprisingly few studies have evaluated the effects of technical editing rigorously .
However there is some evidence that the ' package ' of technical editing used by biomedical journals does improve papers .
A substantial number of references in biomedical articles are cited or quoted inaccurately | BACKGROUND Most journals try to improve their articles by technical editing processes such as proof-reading , editing to conform to ' house styles ' , grammatical conventions and checking accuracy of cited references .
Despite the considerable re sources devoted to technical editing , we do not know whether it improves the accessibility of biomedical research findings or the utility of articles .
This is an up date of a Cochrane methodology review first published in 2003 .
OBJECTIVES To assess the effects of technical editing on research reports in peer- review ed biomedical journals , and to assess the level of accuracy of references to these reports . | To determine the accuracy of the bibliographic citations in theJournal of Anesthesia , all references appearing the years 1987 ( Vol . 1;n=548 ) and 1994 ( Vol . 8;n=1839 ) were sequentially numbered and 100 references from each year were r and omly selected . After citations of non-journal articles were excluded ( n=8 in 1987;n=7 in 1994 ) , the remaining 185 citations were scrutinized . The authors ' names , article title , journal title , volume number , page numbers , and year were examined for each reference . A reference was deemed correct if each clement of the citation was identical to its source . Of the references examined , 41 % and 42 % in 1987 and 1994 , respectively , contained one or more errors . The elements that were inaccurate most often were , in descending order of frequency , article title , author , and page number . No significant differences existed in the error rate between the two years . We have demonstrated a considerable level of citation error in the reference lists of theJournal of Anesthesia articles , and no improvement over the last seven years . We recommend that contributors to theJournal of Anesthesia should carefully check the accuracy of their reference listings Consent forms in research are a source of current and retrospective information for the subject , a " prompt " for the person who is obtaining consent , and a documentation of the " informed " consent process and its adequacy . Occasionally , these forms may be administered by inexperienced trainees or ancillary personnel , and thus st and virtually alone . Therefore , the forms must be inherently comprehensible to the subjects . To test whether this is the case , 65 new applications were r and omly selected from 13 consecutive IRB agendas , and their consent documents were computer-analyzed ( Flesch/Fry scoring ) after correction for expected confounding features , such as lists , tables , and polysyllabic proper names and jargon . Mean U.S. school grade for 70 % comprehension ( Fry score ) was 15.03 + /- 0.19 ( st and ard error of the mean ) , implying readability by 37.4 + /- 1 % of the U.S. adult population . In contrast , a consecutive sampling of 21 Ann L and ers columns yielded a mean Fry score of 7.67 + /- 0.5 ( p < 0.01 ; readable by 75 + /- 3 % ) . Fifteen Reader 's Digest articles yielded a mean Fry score of 9.95 + /- 0.65 ( p < 0.01 ; readable by 59.1 + /- 3 % ) , and 15 " Talk of the Town " columns from The New Yorker averaged a grade level of 13.3 + /- 0.83 ; p < 0.01 ; readable by 42.7 % + /- 4.8 % ) . No document was improved by more than one grade level by the IRB review process , and most were unchanged . ( ABSTRACT TRUNCATED AT 250 WORDS To determine the accuracy of bibliographic citation in Acta Anaesthesiologica Sc and inavica . We review ed all 1990 volumes and part of 1994 volumes of the journal and sequentially numbered all references appearing in those years ( n = 2701 and 2158 in 1990 ( No. 1‐No . 8) and 1994 ( No. 1‐No . 5 ) , respectively ) . We r and omly selected 100 references from each year . After citations of nonjournal articles were excluded , the remaining 195 citations were carefully scrutinized . Authors ' names , article title , journal title , volume number , page numbers , and year w7ere examined in each selected reference . A reference was deemed correct if each element of the citation was identical to its source . Of the examined references , 40 % and 45 % contained one or more errors in 1 990 and 1994 , respectively . The elements most likely to be inaccurate were , in descending order of frequency , article title , author , and page number . No significant differences existed in the error rate between the two years . We have found many citation errors in the reference lists of Acta Anaesthesiologica Sc and inavica and no improvement in these latest four years . All contributors to Acta Anaesthesiologica Sc and inavica should thoroughly check the accuracy of reference lists OBJECTIVE To assess and compare the quality of nonstructured and structured abstract s of original research articles in three medical journals . DESIGN Blind , criterion-based observational study . SAMPLE R and om sample of 300 abstract s ( 25 abstract s per journal each year ) of articles published in the British Medical Journal ( BMJ ) , the Canadian Medical Association Journal and the Journal of the American Medical Association ( JAMA ) in 1988 and 1989 ( nonstructured abstract s ) and in 1991 and 1992 ( structured abstract s ) . MAIN OUTCOME MEASURES The quality of abstract s was measured against 33 objective criteria , which were divided into eight categories ( purpose , research design , setting , subjects , intervention , measurement of variables , results and conclusions ) . The quality score was determined by dividing the number of criteria present by the number applicable ; the score varied from 0 to 1 . RESULTS The overall mean quality scores for nonstructured and structured abstract s were 0.57 and 0.74 respectively ( p < 0.001 ) . The frequency in meeting the specific criteria was generally higher for the structured abstract s than for the nonstructured ones . The mean quality score was higher for nonstructured abstract s in JAMA than for those in BMJ ( 0.60 v. 0.54 , p < 0.05 ) . The scores for structured abstract s did not differ significantly between the three journals . CONCLUSIONS The findings support recommendations that promote the use of structured abstract s. Further studies should be performed to assess the effect of time on the quality of abstract s and the extent to which abstract s reflect the content of the articles CONTEXT The section of a research article most likely to be read is the abstract , and therefore it is particularly important that the abstract reflect the article faithfully . OBJECTIVE To assess abstract s accompanying research articles published in 6 medical journals with respect to whether data in the abstract could be verified in the article itself . DESIGN Analysis of simple r and om sample s of 44 articles and their accompanying abstract s published during 1 year(July 1 , 1996-June 30 , 1997 ) in each of 5 major general medical journals ( Annals of Internal Medicine , BMJ , JAMA , Lancet , and New Engl and Journal of Medicine ) and a consecutive sample of 44 articles published during 15 months ( July 1 , 1996-August 15 , 1997 ) in the CMAJ . MAIN OUTCOME MEASURE Abstract s were considered deficient if they contained data that were either inconsistent with corresponding data in the article 's body ( including tables and figures ) or not found in the body at all . RESULTS The proportion of deficient abstract s varied widely ( 18%-68 % ) and to a statistically significant degree ( P<.001 ) among the 6 journals studied . CONCLUSIONS Data in the abstract that are inconsistent with or absent from the article 's body are common , even in large-circulation general medical journals ABSTRACT Background : We compared the quality of structured abstract s of original research articles from the British Medical Journal ( BMJ ) , Canadian Medical Association Journal ( CMAJ ) , and the Journal of the American Medical Association ( JAMA ) from 1991 to 1992 and 2001 to 2002 and between journals . Methods : A r and om , stratified sample of 54 abstract s from 2001 to 2002 in BMJ , CMAJ , and JAMA was compiled and coded . Two blinded raters review ed 27 abstract s each against 33 objective criteria , separated into eight categories ( purpose , research design , setting , subjects , intervention , measurement of variables , results , and conclusion ) . The quality score was the proportion of criteria present ( range = 0–1 ) . Results : The overall mean quality score ( 0.74 ) for 2001–2002 was significantly higher than the 1988–1989 unstructured abstract s ( mean = 0.57 ; p < 0.001 ) but not different from the 1991–1992 structured abstract s ( mean = 0.74 ; p > 0.05 ) . In 2001–2002 , abstract s of CMAJ and JAMA ( both means = 0.76 ) improved significantly over 1991–1992 ( p < 0.05 ) and scored significantly higher than BMJ ( mean = 0.71 ; d.f . = 16 , p < 0.05 ) . Some individual criteria scores ( intervention , statistical information ) improved but information was found consistently under-represented in areas that imply shortcomings of the studies . Interpretation : We found a consistency in abstract quality regardless of the precise format used by different journals . This indicates that the framework for research articles already in place should be maintained and further modification of the framework may not necessarily improve the abstract quality Publication of medical research has high stakes : the communication and legitimization of medical research , the advancement of authors ' careers , priorities in funding decisions , the direction of future research , and the visibility and prestige of journals themselves . Peer review and editing play central roles in the publication process , affecting the acceptance of a manuscript and the form in which it appears . The most commonly heard justification of peer review is that it is an indispensable aid to an editor in assessing the importance of a scientific question and in assessing how well that question has been answered [ 1 , 2 ] . However , it has also been criticized as being inherently conservative , censorial , and , perhaps worst of all , arbitrary [ 3 ] . A frequently heard charge is that peer review delays the dissemination of crucial medical information without commensurate benefit [ 4 - 7 ] . During the last several years , some medical journal editors decided that the value of peer- review and editing practice s should be examined with the same rigor dem and ed for testing medical hypotheses [ 8 , 9 ] . The First International Congress on Peer Review was organized in 1989 [ 10 ] , bringing together medical journal editors and other interested scholars to present and discuss research on peer review ; a second Congress was held in 1993 . The peer- review process has two components : the assessment s by external review ers and the decisions and actions taken by editors , which are partially affected by comments from the review ers . To our knowledge , no study has evaluated the effects of peer review and editing on manuscript quality once the decision to accept has been made , and a computerized search of Index Medicus back to 1966 failed to locate any such studies . In this paper , we present the results of such a study , assessing the change in a manuscript between the times of provisional acceptance and final publication . We studied whether the quality of accepted manuscripts was improved by peer- review and editorial processes and , if it was , which aspects were most improved . Methods Setting The study was conducted at the editorial offices of Annals of Internal Medicine . Annals , a specialty journal in internal medicine , is published twice monthly and has a circulation of approximately 100 000 . Annals receives approximately 2400 manuscripts annually , of which half are reports of original research . During the period of this study , the investigators included the editors of Annals ( RHF and SWF ) and a statistical associate editor ( SNG ) . The Review Process No change was noted in the usual review and editing procedures at Annals during the time of this study . All manuscripts received at Annals were initially review ed by one of two full-time editors or one of two half-time deputy editors , as well as by one of seven associate editors , all of whom are faculty members of medical schools in Philadelphia and have subspecialty interests ( for example , infectious disease , gastroenterology ) . Half of the su bmi ssions were returned to authors without further review and half were sent to at least 2 outside review ers , selected by the associate editor from a data base of about 7000 review ers . After comments from the review ers were received , the original editor and associate editor reassessed each manuscript and chose which ones would be discussed at a weekly editorial conference of editors , deputy editors , medical associate editors , and two statistical associate editors . Factors that affected acceptance decisions included the quality of the research , the importance of the question , the contribution of the finding to its field , the utility and interest for Annals readers , the quality of the presentation , the priority relative to other articles , and available space . Authors were notified either that the editors would not accept the paper , that the editors were willing to reconsider the paper after major revisions , or that the paper was provisionally accepted , pending satisfactory revision . Approximately one third of the articles evaluated by outside review ers were accepted , 15 % of su bmi tted original research articles . Papers to be considered further were sent to authors , along with the comments of the two outside review ers , comments of one of the statistical editors , and a letter from one of the editors or deputy editors ( which summarized the discussion at the weekly conference , the ideas of the associate editor , and suggestions from the editor ) . In addition , each manuscript was review ed by a production editor , and directions for changes in manuscript wording or layout of figures and tables were included . All revised manuscripts were review ed by the editor or deputy editor in charge of the manuscript , the appropriate associate editor , the statistical editor , and the production editor . Some revised manuscripts were also reassessed by the original outside review ers . Approximately half of the revised manuscripts were returned to authors for further revision . Most revised manuscripts ( > 95 % ) were ultimately published . The time taken by this process was approximately 2 weeks for the initial decision to review or reject , 8 additional weeks to review and make an acceptance decision , 8 weeks until final acceptance , and about 4 months until publication . More than 95 % of manuscripts su bmi tted to Annals had a provisional acceptance or rejection decision sent to the authors within 3 months . The average time from su bmi ssion to publication was about 7 months , with initial peer review accounting for approximately 6 weeks . Manuscript Selection and Study Design All original research manuscripts ( articles ) accepted for publication by Annals from March 1992 to March 1993 were entered into the study after obtaining the author 's consent . Commentaries , review s , expository pieces , editorials , and brief reports were not included . This study had a beforeafter design , in which two versions of each manuscript were evaluated : the version originally su bmi tted and the version sent to the printer for publication after all modifications based on peer review , editors ' comments , and copyediting . All before and after manuscripts were in electronic form and were reformatted to make the appearance of the two versions identical . Authors ' names and affiliations were removed . The design of the study was approved by the Institutional Review Board of the University of Pennsylvania School of Medicine . Definition of Quality Manuscript quality can be separated conceptually into two components : the quality of the research itself , and the quality of the research report . The quality of the research report was evaluated in this study . It was defined as follows on the cover sheet of the quality assessment instrument : Whether the authors have described their research in enough detail and with sufficient clarity so a reader could make an independent judgment about the strengths and weaknesses of their data and conclusions . Manuscript Quality Assessment Instrument A 34- question instrument was developed to structure the assessment of the quality of a manuscript ( Appendix ) . Items were derived from published checklists [ 11 - 14 ] , articles about the contents of journal articles [ 15 - 18 ] , the authors ' editorial experience , and the comments of journal editors and method ologists who review ed drafts of the instrument . Each question could be answered on a 5-point ordinal scale , where 1 was worst and 5 was best . The instrument was organized along the same dimensions as a st and ard journal article : Title and Abstract ( 2 items ) , Introduction ( 2 items ) , Methods ( 7 items ) , Results ( 15 items ) , Discussion and Conclusions ( 4 items ) , and General Evaluation ( 4 items ) . An additional question asked for a subjective assessment of the manuscript 's overall quality on a 10-point scale . The instrument differed from previously published quality scoring schemes in several ways . It was not a checklist but rather was a set of structured judgments , grade d ordinally , allowing users the discretion not to penalize a manuscript if a detail was omitted that was not critical to the study 's interpretation . Also , in keeping with the definition of quality given above , each question was about the adequacy of the reporting rather than the quality of the research itself . Assessment A panel of 44 physicians and epidemiologists with training in research methods and in critically assessing the medical literature was recruited to serve as an independent panel of expert assessors ( experts ) . They did not receive any formal training in the use of the assessment instrument , although general guidelines were given on the cover sheet ( Appendix ) . The panel was masked to the design and aims of the study ; they were told only that they were participating in a study of manuscript quality for Annals . Before and after versions of each manuscript were r and omly assigned to different experts to prevent the bias that might have been introduced if they could infer the design of the study and thereby which manuscript had been through the editorial process . Thirty-two manuscript versions were given to two or three experts to assess the reliability of the instrument ; all others were assessed by only one expert . Statistical Analyses The study was design ed to have 90 % power to detect a 0.5 unit change in average score , assuming a within-manuscript st and ard deviation of 1 scale unit , using = 0.05 . The main outcome measure was the percentage of items that were scored 3 or higher on the 5-point scales ( percentage score ) . The average of all score components ( average score ) was also analyzed . Linear regression was used to assess the effect of revision on each of these outcome measures , with terms controlling for manuscript and review er . Item-specific analyses were done on dichotomized item scores ( 0 for ratings 2 and 1 for ratings 3 ) . The change from before revision to after revision in individual items was statistically assessed with conditional logistic regression , which allowed for variable group OBJECTIVES To evaluate the accuracy of bibliographic references in REVISTA ESPANOLA DE ANESTESIOLOGIA Y REANIMACION ( REDAR ) and compare it with other Spanish and international journals . MATERIAL AND METHODS One hundred references were selected at r and om from those published in REDAR during 1994 . A citation was considered correct if there were no differences between it and the original article in any of 6 st and ard citation times , and if it complied with REDAR citation style . A citation was considered incorrect if there were in fact differences or if REDAR style was not followed . Errors that interfered with direct access to the original were considered serious . Also considered serious were the omission of the first author . RESULTS Some type of error was detected in 53.9 % of the references . Twelve contained a serious error , which on 5 occasions impeded finding the original article and on 6 occasions made direct access difficult . The first author was missing in 1 citation . Errors were found , in order of decreasing frequency , in authors , article titles , journal title , volume , pages and year . A single error was found in 28 citations , 2 were found in 12 , 3 were found in 2 and more than 3 were found in 1 . CONCLUSIONS REDAR 's rate of error in references is comparable to the rates of other Spanish journal , but it is nearly double that of international journals in anesthesiology with higher impact factors ( Anesthesiology , Canadian Journal of Anaesthesia ) . An effort must be made by authors and editors to remedy the situation BACKGROUND The reference list is an important part of a scientific article . To be useful it must be accurate . OBJECTIVE The purpose of this study was to evaluate the accuracy of references in the dermatologic literature . METHODS We r and omly selected 240 references ( 60 per journal ) from the Archives of Dermatology , the British Journal of Dermatology , this Journal , and the Journal of Investigative Dermatology and checked them against the original articles . RESULTS The overall rate of citation error ( the information identifying the source ) was 41 % , and the quotation error ( inconsistency between the statement referenced and the original source ) was 35 % . Only 36 % of references were free of error . CONCLUSION This study shows that the rate of citation and quotation errors is unacceptably high in the dermatologic literature , which significantly diminishes the value of the reference list The purpose of this study was to determine the accuracy of referenced statements in review articles focused on drug therapy . Review articles published between January and December 1987 in Clinical Pharmacy , DICP , Drugs , and Pharmacotherapy were used . Ninety-nine references from these articles were r and omly selected and pulled to determine if the published study results were in agreement with the review article statement . These references accounted for 165 statements . Thirty-nine of 165 statements in the review articles ( 24 percent ) were found to be inappropriate when compared with the original references . These inappropriate quotations were classified as either wrong , misleading , or deriving from only the discussion section of the original article . There is a need for increased awareness by authors to differentiate between reported results , article hypothesis , and their own interpretations , as well as for accuracy in quotation The high rate of citation errors in bibliographies in medical journals has been a source of concern in recent years . We examined the accuracy of references published during 1 year in two Israeli medical journals . Only two-thirds of the r and omly selected references examined were error free ; 8 % had major errors preventing identification of the cited article . Most of the errors found ( 76 % ) were in referencing the author(s ) or title of the article . We conclude that errors in citation appear also in Israeli medical journals . Editors should emphasize the importance of reference verification ; however , primary responsibility for the accuracy of the reference list rests with the author . Authors should exercise more care in preparing bibliographies and should invest more effort in verification of quoted references BACKGROUND Previous studies have noted the prevalence of errors in journal reference lists , including nursing journals , but an in-depth study of nursing research journals has not been repeated . OBJECTIVES The purpose of this study was to determine the number and types of errors in nursing research journal reference lists . METHOD A stratified r and om sample of 262 references from three nursing research journals was obtained . References were compared with the actual articles , books , and chapters cited , or with photocopies obtained via interlibrary loan . Error rates were calculated . RESULTS The overall error rate was 45.8 % ; 38.3 % of all references contained at least one major error , and 13.8 % of all references contained at least one minor error . CONCLUSIONS The overall rate of reference errors falls within the range exhibited by recent studies of the medical and dental literature but exceeds the rates found in studies of nursing journals and veterinary medicine journals . Research ers need to consider the number and types of errors involved when using reference lists in their research Abstract Objective : To examine the effect of the method of data display on physician investigators ' decisions to stop hypothetical clinical trials for an unplanned statistical analysis . Design : Prospect i ve , mixed model design with variables between subjects and within subjects ( repeated measures ) . Setting : Comprehensive cancer centre . Participants : 34 physicians , stratified by academic rank , who were conducting clinical trials . Interventions : Participants were shown tables , pie charts , bar graphs , and icon displays containing hypothetical data from a clinical trial and were asked to decide whether to continue the trial or stop for an unplanned statistical analysis . Main outcome measure : Percentage of accurate decisions with each type of display . Results : Accuracy of decisions was affected by the type of data display and positive or negative framing of the data . More correct decisions were made with icon displays than with tables , pie charts , and bar graphs ( 82 % v 68 % , 56 % , and 43 % , respectively ; P=0.03 ) and when data were negatively framed rather than positively framed in tables ( 93 % v 47 % ; P=0.004 ) . Conclusions : Clinical investigators ' decisions can be affected by factors unrelated to the actual data . In the design of clinical trials information systems , careful consideration should be given to the method by which data are framed and displayed in order to reduce the impact of these extraneous factors A previous study indicated that there were many citation errors in the Canadian Journal of Anaesthesia After this report , editors of the Journal requested any contributors , whose papers were accepted for publication , to verify the accuracy of reference citation by including a photocopy of the first page of each reference . The present study examined if the accuracy of the reference list had improved . We compared citation errors between volumes of 1990 and 1994 . One hundred references from each year ’s publication were r and omly selected . After citations of nonjournal articles were excluded , the remaining 190 citations were carefully scrutinized . Authors ’ names , article title , journal title , volume number , page numbers , and year were examined in each selected reference . A reference was deemed correct if each element of the citation was identical to its source . Of the examined references , 48 % and 22 % contained one or more errors in 1990 and 1994 , respectively . Errors in the title and author field of citation were most common in the either of the two years , occurring in about 70 % of the references which contained some errors . Citation errors in Canadian Journal of Anaesthesia were considerably improved after the request to verify citation accuracy . Although this check-system probably contributes to the improvement of accuracy of reference citation , the rate of citation errors remains high . We believe that contributors’efforts will enhance the value of the journal . RésuméUne étude antérieure a décelé , dans le Journal Canadien d’Anesthésie , un gr and nombre d’erreurs bibliographiques . Par la suite , les éditeurs ont dem and é aux collaborateurs de la revue do nt les articles étaient acceptés pour publication , de vérifier l’exactitude des références et de fournir une photocopie de la première page de chacune des celles-ci . L’étude actuelle avait pour but de vérifier s’il en avait résulté une plus gr and e exactitude pour les références . Nous avons comparé les erreurs bibliographiques entre les volumes 1990 et 1994 . Cent références pour chacune des années de publication ont été sélectionnées au hasard . Après l’élimination de celles qui ne provenaient pas de revues , les 190 références résiduelles ont été examinées soigneusement . Le nom des auteurs , le titre de l’article , le litre du journal , le numéro du volume , les numéros de pages , et l’année ont été vérifiés dans cet ordre . Une référence était jugée correcte si chacun des ses éléments était identique à sa source . Des références étudiées , 48 % et 22 % contenaient respectivement une erreur ou plus en 1990 et en 1994 . Les erreurs de litres et d’auteurs étaient les plus fréquentes pour chacune des deux années et survenaient dans 70 % des cos de références erronées . Les erreurs bibliographiques ont considérablement diminué dans le Journal Canadien d’Anesthésie après cette dem and e de vérification . Bien que ce système aide à améliorer la fidélité des références , le taux d’erreurs demeure élevé . Nous croyons que les efforts de la part des collaborateurs du Journal continueront d’améliorer son calibre Citation and quotation errors are common in medical journals . We assessed the prevalence of those errors in gross anatomy journals , where articles often cite old anatomical studies . The study included 199 r and omly selected references from articles published in the first 2001 issue of three major gross anatomy journals : Annals of Anatomy , Clinical Anatomy , and Surgical and Radiologic Anatomy . The selected references were checked for accuracy against the original articles . Citation errors were classified as major , intermediate , and minor . Quotation errors were classified as major and minor . Citations errors were found in 27 % ( 54/199 ) of the references and 38 % of them were major errors . Errors occurred in 19 % ( 52/272 ) of quotations and nearly all ( 94 % ) were major . Furthermore , 24 % of the quotations were indirect references to a secondary , instead of original , source . There was no statistically significant difference in the rates of citation or quotation errors between the references published before or after the introduction of MEDLINE ( χ2 test , P > 0.05 ) in 1963 , and the prevalence of these errors in gross anatomy journals was similar to that found in other medical fields . A high proportion of major citation errors , a very high proportion of major quotation errors , and the substantial number of indirect quotations call for serious editorial action in anatomy journals . Clin . Anat . 17:534–539 , 2004 . © 2004 Wiley‐Liss , The purpose of this study was to quantify and classify errors in reference lists of r and omly selected , recently published issues of nursing journals ( n = 17 ) and to assess whether these errors prevented retrieval of the cited documents . R and omly selected references , 65 from clinical journals and 47 from non- clinical journals , were compared to the original sources for accuracy . Errors were classified as minor ( not preventing retrieval ) and major ( preventing retrieval ) . Errors occurred more frequently in references in clinical journals , 38.4 % of those review ed , as compared to 21.3 % in of non- clinical journals . Additionally , 4.6 % of the clinical references contained major errors , but no major errors were located in references from the non- clinical journals . These findings have implication s for all readers CONTEXT Structured abstract s , that is , abstract s that describe a study using requisite content headings , provide more informative content . Concomitant reporting in the text of the report might improve with structured abstract use because of increased awareness by authors or editors of important study areas associated with content headings . OBJECTIVE To assess whether structured abstract use is associated with improved reporting of r and omized clinical trials . DESIGN AND SETTING Survey of trial reports published the year preceding , of , and following new use of structured abstract s , found by h and search ing Archives of Ophthalmology ( 1992 - 1994 ) and Ophthalmology ( 1991 - 1993 ) , as well as trial reports published concurrently without change in abstract format ( American Journal of Ophthalmology , 1991 - 1994 ) . MAIN OUTCOME MEASURES We measured the inclusion of 56 criteria derived from Consoli date d St and ards of Reporting Trials ( CONSORT ) descriptors ( JAMA 1996;276:637 - 639 ) in the text of each report and calculated the number of criteria included per report and the proportion of reports including individual criteria . Reports with structured abstract s were compared with those without , and reports published in 1993 and 1994 in the American Journal of Ophthalmology were compared with those published in 1991 and 1992 . RESULTS The mean ( SEM ) number of criteria included by authors was 15.8 ( 0.4 ) per report in 125 trial reports . We found no difference in the mean number of criteria included or the proportion of reports that included specific criteria by journal . Following structured abstract use , there was no difference in either the mean number of criteria per report or the proportion of reports including a majority of criteria within each CONSORT subheading . Four criteria were included more often and 2 less often following structured abstract use in individual journals . CONCLUSION Using CONSORT descriptor criteria to evaluate reporting quality , we found no difference in text reporting associated with structured abstract use in the journals examined Readers need information about the design and analysis of a clinical trial to evaluate and interpret its findings . We review ed 84 therapeutic trials appearing in six general surgical journals from July 1981 through June 1982 and assessed the reporting of 11 important aspects of design and analysis . Overall , 59 % of the 11 items were clearly reported , 5 % were ambiguously discussed , and 36 % were not reported . The frequency of reporting in general surgical journals is thus similar to the 56 % found by others for four general medical journals . Reporting was best for r and om allocation ( 89 % ) , loss to follow-up ( 86 % ) , and statistical analyses ( 85 % ) . Reporting was most deficient for the method used to generate the treatment assignment ( 27 % ) and for the power of the investigation to detect treatment differences ( 5 % ) . We recommend that clinical journals provide a list of important items to be included in reports on clinical trials BACKGROUND The accuracy of reference citations in The Australian and New Zeal and Journal of Surgery was evaluated . All of the references from 1995 ( Volume 65 ) were included ( n = 4092 ) . METHODS A sample of 100 references was r and omly selected and examined in detail by comparison with the original references . RESULTS Overall , 60 % of citations contained errors . Errors were categorized by dividing references into six elements . A total of 38.8 % of citations contained an error in one element , 15.6 % contained errors in two elements , 4.4 % contained errors in three elements , and 4.4 % contained errors in four elements of the reference . The most common errors were errors of authors ' names and errors in the title . CONCLUSIONS Contributors to this journal should take more care in checking references in the manuscripts before publication Results from original studies are not always correctly represented in subsequent medical publications . In this study , r and omly selected quotations from Israeli medical journals were examined . Less than 80 % of the examined statements were in complete agreement with the original source . In about 7 % the cited reference failed to substantiate the previous author 's statement . Similar results were found over a range of American and European general and speciality journals . It is concluded that errors in quotation are a widespread problem in the biomedical literature . Editors and peer review ers can improve quotation accuracy by stressing this issue in decisions regarding publication . Nevertheless , it seems that the most efficient solution would be for authors to increase their vigilance in accurately quoting results and statements from previous publications BACKGROUND AND PURPOSE The purpose of this study was to determine whether an example in a technical research report would affect application of content to hypothetical patient problems and to future patients . SUBJECTS Subjects were 69 physical therapists who routinely used isokinetic equipment in the treatment of patients with knee joint pathologies . METHODS Thirty-five subjects ( group 1 ) read a research report that described mathematical models for predicting preinjury quadriceps femoris and hamstring muscle performance . The report included an example of applying the information . The remaining 34 subjects ( group 2 ) read the same research report with the example omitted . Subjects were asked to select appropriate prediction models and determine preinjury knee torques for two hypothetical patients . Subjects were also contacted 6 to 12 weeks after initial data collection to determine whether they had applied research report results in their treatments of patients . RESULTS Chi-square analyses indicated manuscript type was not related to the selection of correct models , but group 1 subjects computed correct torque values more frequently than did group 2 subjects . Insufficient data were available regarding application of research report content to patients . CONCLUSION AND DISCUSSION The results indicate application of technically oriented research reports may be enhanced by including examples of applications . ( Gross MT , Sekerak DK , Allen DD . Effect of including a clinical example on the ability of physical therapists to apply information in a technical research report BACKGROUND Structured abstract s have been widely adopted in medical journals , with little demonstration of their superiority over unstructured abstract s. OBJECTIVES To compare abstract quality among 3 clinical dermatology journals and to compare the quality of structured and unstructured abstract s within those journals . DESIGN AND DATA SOURCES Abstract s of a r and om sample of clinical studies ( case reports , case series , and review s excluded ) published in 2000 in the Archives of Dermatology , The British Journal of Dermatology , and the Journal of the American Academy of Dermatology were evaluated . Each abstract was rated by 2 independent investigators , using a 30-item quality scale divided into 8 categories ( objective , design , setting , subjects , intervention , measurement of variables , results , and conclusions ) . Items applicable to the study and present in the main text of the article were rated as being present or absent from the abstract . A global quality score ( range , 0 - 1 ) for each abstract was established by calculating the proportion of criteria among the eligible criteria that was rated as being present . A score was also calculated for each category . Interrater agreement was assessed with a kappa statistic . Mean + /- SD scores were compared among journals and between formats ( structured vs unstructured ) using analysis of variance . MAIN OUTCOME MEASURES Mean quality scores of abstract s by journal and by format . RESULTS Interrater agreement was good ( kappa = 0.71 ) . Mean + /- SD quality scores of abstract s were significantly different among journals ( Archives of Dermatology , 0.78 + /- 0.07 ; The British Journal of Dermatology , 0.67 + /- 0.17 ; and Journal of the American Academy of Dermatology , 0.64 + /- 0.15 ; P = .045 ) and between formats ( structured , 0.71 + /- 0.11 ; and unstructured , 0.56 + /- 0.18 ; P = .002 ) . The setting category had the lowest scores . CONCLUSIONS The quality of abstract s differed across the 3 tested journals . Unstructured abstract s were demonstrated to be of lower quality compared with structured abstract s and may account for the differences in quality scores among the journals . The structured format should be more widely adopted in dermatology journals Effectiveness of melanoma prevention depends on how it is accepted by the population . Humour and alarmism are often used in campaigns , but no information is available about how much they may improve or limit the impact of a campaign . Three different leaflets containing the same information about sun exposure and skin cancers were developed using three different tones of presentation : humoristic ( H‐leaflet ) , alarmist ( A‐leaflet ) or neutral information ( N‐leaflet ) . In this r and omized controlled study , each type of leaflet was mailed to a sample of 300 subjects representative of the sociodemographic population of the South of France . A fourth sample to whom no leaflet was sent was used as a control . Fifteen days after the mailing , the 1200 individuals were interviewed by phone . Four hundred and forty‐four of the 900 who received the mail read the leaflet . The percentage of individuals with a good awareness of melanoma was higher in leaflet groups than in controls . The percentage of individuals who read a leaflet was lower in the A‐leaflet group and the percentage of individuals knowing what a melanoma is tended to be lower in the H‐leaflet group . There was no significant difference between groups with regard to ability for self‐ assessment of skin sun sensitivity , risk factors and sun exposure . The tone of presentation seems to have a limited impact on the effect of a campaign , but alarmism tends to reduce the number of people reached by the message whereas humour tends to decrease the impact of the message BACKGROUND The reference list is an important part of a scientific article . To be useful , it must be accurate . METHODS To evaluate the reference accuracy in the Journal of Dermatology and the Korean Journal of Dermatology , we r and omly selected 100 references from each journal and checked them against the original articles . RESULTS The overall rate of citation errors was 24 % in the Journal of Dermatology and 33 % in the Korean Journal of Dermatology . Errors in the title and author names were common , each occurring in about half of the citation errors . The overall rate of quotation errors was 14 % in the Journal of Dermatology and 27 % in the Korean Journal of Dermatology . CONCLUSIONS This study shows that the rate of citation errors is unacceptably high in the Journal of Dermatology and the Korean Journal of Dermatology , which significantly diminishes the value of the reference list . We would strongly urge that the peer review of citation and quotation accuracy should be strengthened A high rate of errors of citation and quotation has been reported in the publications of many medical specialties . The aim of this study was to determine the prevalence of citation and quotation errors in otolaryngology/head and neck surgery journals . A retrospective analysis was performed based on the first issue for 1997 of each of four journals : Laryngoscope ; Annals of Otology , Rhinology and Laryngology ; Clinical Otolaryngyology ; and Journal of Laryngology and Otology . A sample of 50 references from each journal was r and omly selected and each was checked for accuracy against the original referenced paper . Citation errors were categorized as major , intermediate or minor and quotation errors as major or minor . Citation errors occurred in 37.5 % of the references , 11.9 % of which were considered major errors . Quotation errors occurred in 17 % , with 11.1 % major errors . This prevalence is similar to the established error rate in medical literature STUDY OBJECTIVE To determine the incidence and nature of errors in the citation and quotation of references contained in the emergency medicine literature . DESIGN A retrospective analysis of a r and om sample of articles and references found in the three major emergency medicine journals . SETTING A university/county hospital . METHODS We examined single issues of three emergency medicine journals : Annals of Emergency Medicine , Journal of Emergency Medicine , and American Journal of Emergency Medicine . INTERVENTIONS None . MEASUREMENTS Four independent review ers assessed 145 references from 46 referring authors for citational and quotational accuracy . MAIN RESULTS Major and minor citation errors were found in 10.3 % and 17.2 % of reference listings , respectively . Qualitative quotational errors were found in 35.2 % of references . Eighty-two percent of these errors were considered to be major . Quantitative quotational errors were found in 47 % of references review ed . Secondary rather than primary reference sources were used in 41.4 % of references review ed . CONCLUSION This study demonstrates a substantial error rate in the citation and quotation of reference sources in the emergency medicine literature . In addition , verification of primary source material was not done by a large percentage of the authors review ed . Recommendations for improving the accuracy of the emergency medicine literature are offered Purpose A patient 's willingness to consent to a procedure may be influenced by various factors , including the patient 's rapport with the physician , nonverbal cues he or she receives during the discussion of risks , and other elements of the discussion of risks . Previous reports address these influences , but the effect of the actual wording used to describe risks is unclear . The purpose of this study was to better underst and how framing the risk involved in a procedure affects a patient 's likelihood to consent to the procedure . Method In a 1997 study at the Clevel and Clinic Foundation , the authors r and omly assigned 116 patients to view one of two short videos describing angioplasty and its associated risks . Sixty-three participants viewed the first video , which framed the procedure as 99 % safe , and 53 viewed the second , which framed the likelihood of complication as 1 in 100 . Participants were then asked to rate their consent to two hypothetical treatment scenarios on a four-point Likert-type scale ( 1 = definitely , 4 = definitely not ) . Results When asked to consent to a treatment scenario that would relieve chest pain but offer no survival benefit , respondents who viewed the first video were more likely to consent than were those who viewed the second ( p < .001 ) . There was no significant difference in the two groups ' likelihoods to consent when the potential health benefit was to reduce the risk of future heart attack . Conclusion This study 's finding provides evidence that how a physician describes a procedure 's risks when obtaining a patient 's informed consent significantly influences the likelihood of consent . This fact should be considered when teaching communication skills , including interviewing and patient education skills , so that patients will be more likely to make health care decisions that are consistent with their own values and beliefs OBJECTIVE Errors in reference citation and use are common in the medical and scientific literature . The prevalence of such errors in the radiology literature has not been reported . We did a study to assess the accuracy and appropriateness of use of references cited in two general radiology journals . MATERIAL S AND METHODS All references cited in the June 1993 issues of the American Journal of Roentgenology and Radiology were numbered consecutively . Fifty references were chosen at r and om from each journal , and copies of the original publications were obtained from the medical library at our institution or through interlibrary loan . Each reference was studied for accuracy and appropriateness of its citation in the June 1993 journal article ( the " index article " ) . Errors were classified as major or minor in each category . Data were analyzed with the SAS statistical package . RESULTS Forty-seven ( 94 % ) of 50 references were obtained from AJR , and 48 ( 96 % ) of 50 from Radiology . Of the 47 from the AJR , one ( 2 % ) had a major error and 21 ( 45 % ) had a minor error in accuracy . Of the 48 from Radiology , two ( 4 % ) had a major error and 11 ( 23 % ) had a minor error in accuracy . These values were significantly different for minor errors ( p = .0188 ) , but not for major ones ( p = 1.000 ) . When we adjusted for index article type , error rates for the two journals were not significantly different ( p = .0612 ) . We found four major errors ( 9 % ) and two minor errors ( 4 % ) in appropriateness of citation in the AJR references we studied . Three references ( 6 % ) from Radiology contained major errors in appropriateness of use ; we found no minor errors of that type . These values were not significantly different ( p = .232 for minor errors ; p = .709 for major errors ) . One error in accuracy prevented location of the original reference . Errors were not related to the number of references cited in an index article ( p = .528 for accuracy ; p = .092 for appropriateness ) . CONCLUSION The rate of minor errors in accuracy of references is fairly high in the two journals studied and is comparable to rates previously reported for other types of journals . The rate of major errors in accuracy of references is slightly lower than rates for other types of journals . The percentage of cited references that could not be located was also smaller than in previous reports . Errors in citation appropriateness were less common as well . Given the small number of errors that prevented references from being located , significant expenditure of time and money by journal staff members in checking references is probably not justified . However , authors should be encouraged to exercise greater care in checking all of their references for both accuracy and appropriateness of use . Differences in error rates between AJR and Radiology may have result ed in part from the r and om sampling method , which produced different mixtures of index articles for the two journals We have review ed the reference citations in volume 1 ( 1995 ) and volume 2 ( 1996 ) of the Hong Kong Medical Journal to determine their accuracy . One hundred references were r and omly selected from each volume . After excluding references not from indexed journals , all citations were examined in detail by dividing them into six component elements and comparing them with the original . We found that 61 % of references in volume 1 and 51 % of references in volume 2 contained inaccuracies , giving an overall error rate of 56 % . Thirty-eight percent of references contained errors in one element , 16 % contained errors in two elements , and 2 % contained errors in three or more elements . The most common errors were those of the title or authors ' names . The rate of citation errors in the Hong Kong Medical Journal is at the high end of the range compared with other medical journals . Contributors to this journal need to take more care in checking their references before publication CONTEXT The most-read section of a research article is the abstract , and therefore it is especially important that the abstract be accurate . OBJECTIVE To test the hypothesis that providing authors with specific instructions about abstract accuracy will result in improved accuracy . DESIGN R and omized controlled trial of an educational intervention specifying 3 types of common defects in abstract s of articles that had been review ed and were being returned to the authors with an invitation to revise . MEAN OUTCOME MEASURE Proportion of abstract s containing 1 or more of the following defects : inconsistency in data between abstract and body of manuscript ( text , tables , and figures ) , data or other information given in abstract but not in body , and /or conclusions not justified by information in the abstract . RESULTS Of 250 manuscripts r and omized , 13 were never revised and 34 were lost to follow-up , leaving a final comparison between 89 in the intervention group and 114 in the control group . Abstract s were defective in 25 ( 28 % ) and 30 ( 26 % ) cases , respectively ( P=.78 ) . Among 55 defective abstract s , 28 ( 51 % ) had inconsistencies , 16 ( 29 % ) contained data not present in the body , 8 ( 15 % ) had both types of defects , and 3 ( 5 % ) contained unjustified conclusions . CONCLUSIONS Defects in abstract s , particularly inconsistencies between abstract and body and the presentation of data in abstract but not in body , occur frequently . Specific instructions to authors who are revising their manuscripts are ineffective in lowering this rate . Journals should include in their editing processes specific and detailed attention to abstract PURPOSE To evaluate the quality of reporting of all the new r and omized clinical trials published during 1999 in OPHTHALMOLOGY : using the CONSORT statement parameters . DESIGN Descriptive series of published studies . STUDIES INCLUDED R and omized clinical trials . METHODS Eligible studies were all r and omized clinical trials published in Volume 106 ( 1999 ) of OPHTHALMOLOGY : that reported the results of prospect ively conducted studies in humans comparing two or more therapeutic options with regard to their effect on one or various outcomes , in which the authors stated that a process of r and omization or quasi-r and omization was performed before the interventions . Each study was evaluated by two independent observers establishing the specific report in the published manuscript of 57 CONSORT statement descriptors , and consensus was obtained between evaluators . MAIN OUTCOME MEASURES Overall presence of CONSORT statement descriptors in published reports . RESULTS The mean number of positive CONSORT descriptors for the 24 eligible r and omized clinical trials was 33.42 ( st and ard error of the mean [ SEM ] 1.57 ) of 57 possible . This score was significantly different ( P : < 0.001 ) from the score of 16.6 ( st and ard error of the mean 0.6 ) reported for OPHTHALMOLOGY : in the 1991 to 1994 study by Scherer and Crawley . Of the nine descriptors measuring the quality of abstract reporting , a mean of 6.25 ( SEM 0.3 ) was included in the 24 study abstract s evaluated , significantly different from the Scherer and Crawley score ( 5.2 , SEM 0.2 . P : < 0.001 ) . Four and six descriptors increased and decreased , respectively , their reporting in more than 20 % . Key descriptors such as hypothesis postulation , primary outcome determination , sample size calculations , and a discussion of the limitations of the study such as bias , imprecision , and internal validity are still reported in less than 42 % of clinical trials . CONCLUSIONS This study describes for the first time after the adoption of the CONSORT statement recommendations the status on the quality of reporting of recently published r and omized clinical trials in OPHTHALMOLOGY : Although not a direct measure of the intrinsic quality of a study , reporting quality provides the reader with useful tools for the evaluation of its validity . The quality of reporting of r and omized clinical trials shows an overall improvement when compared with the period between 1991 and 1994 . However , there is still significant room for improvement , especially in descriptors essential for the validation of clinical trial results that are still widely underreported Reference lists serve as a re source for the reader and provide support for the author 's ideas . Errors in references reflect poorly on the author and journal and may prevent locating the referenced articles . The purpose of this study was to determine the number and types of errors in references in 3 critical care nursing journals : Journal of PeriAnesthesia Nursing , American Journal of Critical Care , and Critical Care Nurse . There were 2,444 citations in 13 issues of these journals during the study period . Ten percent of the references from each journal was selected r and omly and analyzed for accuracy . Of the 244 references examined , 56 contained errors for an overall error rate of 22.9 % . Major errors , such as misspelled or omitted author names and initials , occurred in 19.6 % of the references . Minor errors , including non-first page discrepancies , occurred in 4.5 % of the references . Errors in author names combined with incorrect or missing volume or issue numbers were the 2 most common errors , accounting for 61 % of errors . The overall error rate for these 3 critical care nursing journals was lower than the rates reported for other nursing journals Previous studies have examined the bibliographic accuracy of citations in medical journals . The purpose of this study was to assess reference accuracy in five national dental journals . One hundred references were r and omly selected from the March , 1987 , issue of each of five dental journals ( a total of 500 references ) . Each reference was verified either from the original source or from other indexing tools if the original was unavailable . References were divided into two categories : incorrect and correct . The number of incorrect references was counted and subdivided into major and minor errors . The errors were grouped by types of error : author , article title , citation ( which included errors in journal title , volume , issue , and page numbers ) , and " unable to verify " . This survey found 211 ( 42 % ) inaccuracies out of 500 references review ed , with a total of 248 errors within the incorrect group . Out of the latter , 173 ( 70 % ) were minor errors , and 75 ( 30 % ) were major errors . Types of minor errors ranked as follows : minor article title errors , 86 ( 35 % ) ; minor author errors , 61 ( 25 % ) ; and minor citation errors , 26 ( 10 % ) . Types of major errors were ranked as follows : incorrect journal citation , 32 ( 13 % ) ; " unable to verify " , 25 ( 10 % ) ; incorrect author , 10 ( 4 % ) ; and incorrect article title , 8 ( 3 % ) . The results of this survey showed that nearly half of the references review ed were inaccurate PURPOSE An accurate listing of cited references in journal articles is important for the reader . Many studies have revealed errors in the references cited in a variety of subspecialty journals . We believe that a similar amount of errors , relative to other subspecialty journals , exists in the Journal of H and Surgery . METHODS One hundred r and omly selected references from each of the 1985 and 1995 Journal of H and Surgery volumes were analyzed for accuracy of the journal name , title , author name(s ) , year , volume , and page number(s ) . References were considered without error if they matched the original article exactly . RESULTS In 1985 , 30 % of the references examined contained one or more errors as compared with 11 % in 1995 . CONCLUSIONS These error rates are similar to those found in studies of other biomedical journals . Perhaps the decrease in the quantity of errors present in 1995 versus that of 1985 is related to the implementation of a more stringent , revised set of instructions to su bmi tting authors imposed in 1995 PURPOSE To determine the accuracy of bibliographic citations in three widely circulated nursing journals , RN , Nursing Management , and Image : Journal of Nursing Scholarship . Accurate citations facilitate retrieval of the cited documents and establish the judgment and credibility of authors . DESIGN Descriptive , comparative . METHODS A r and om sample of 60 references per journal published July 1995 to June 1996 was review ed for citation and quotation accuracy . Errors were classified as major or minor . Data were analyzed using the SAS statistical package . FINDINGS Of the 180 references , 58 ( 32 % ) had citation errors , with 43 of 58 errors classified as major errors , which made retrieval of the cited work difficult ; 12 of the 180 articles contained a major quotation error , including four instances where the content of the original article contradicted or was unrelated to the author 's contention . CONCLUSIONS The rate of citation and quotation errors in the three sample d nursing journals is comparable to rates previously reported for medical and nursing journals . Errors of citation and quotation diminish the value of published papers BACKGROUND Reports of clinical trials often lack adequate descriptions of their design and analysis . Thus readers can not properly assess the strength of the findings and are limited in their ability to draw their own conclusions . A review of 6 surgical journals in 1984 revealed that the frequency of reporting 11 basic elements of design and analysis in clinical trials was only 59 % . This study attempted to identify areas that still need improvement . METHODS Eligible studies published from July 1995 through June 1996 included all reports of comparative clinical trials on human subjects that were prospect i ve and had at least 2 treatment arms . A total of 68 articles published in 6 general surgery journals were review ed . The frequency that the previously identified 11 basic elements of design and analysis were reported was determined . RESULTS Seventy-four percent of all items were reported accurately ( a 15 % increase from the previous study ) , 4 % were reported ambiguously , and 23 % were not reported ; improvement was seen in every journal . The reporting of eligibility criteria and statistical power improved the most . For 3 items , reporting was still not adequate ; 32 % of reports provided information about statistical power , 40 % about the method of r and omization , and 49 % about whether the person assessing outcomes was blind to the treatment assignment . CONCLUSIONS Improvements have been made in reporting surgical clinical trials , but in general method ologic questions poorly answered in the 1980s continue to be answered poorly in the 1990s . Editors of surgical journals are urged to provide authors with guidelines on how to report clinical trial design and analysis To determine the accuracy of bibliographic citation in the anesthesia literature , we review ed all 1988 volumes of ANESTHESIOLOGY , Anesthesia and Analgesia , British Journal of Anaesthesia , and Canadian Journal of Anaesthesia and sequentially numbered all references appearing in that year ( n = 22,748 ) . One hundred references from each of the four journals were r and omly selected . After citations to nonjournal articles ( i.e. , books or book chapters ) were excluded , the remaining 348 citations were analyzed in detail . Six st and ard bibliographic elements— authors ' names , article title , journal title , volume number , page numbers , and year — were examined in each selected reference . Primary sources were review ed , unless our institution did not own the source or could not obtain it through interlibrary loan , in which case st and ard indexes , abstract ing services , and computerized data bases were consulted . Each element was checked for accuracy , and references were classified as either correct or incorrect . A reference was correct if each element of the citation was identical to its source . Of the examined references , more than half ( 50.3 % ) contained an error in at least one element . The elements most likely to be inaccurate were , in descending order , article title , author , page numbers , journal title , volume number , and year . No significant differences ( P = 0.283 ) existed in the error rates of the four journals ; the percentage of citations containing at least one error ranged from 44 % ( Anesthesia and Analgesia ) to 56 % ( British Journal of Anaesthesia ) . The citation error rate of anesthesia journals is similar to that reported in other specialties , where error rates ranging from 38 % to 54 % have been documented Purpose : To identify the frequency and types of reference errors in neonatal-maternal nursing literature . This study was an extension of earlier research on reference accuracy in pediatric and critical care nursing journals . Design : A r and om sample was selected of references in three nursing journals : Neonatal Network : The Journal of Neonatal Nursing ; Journal of Obstetric , Gynecologic , and Neonatal Nursing ; and The American Journal of Maternal/Child Nursing . References were compared against original publications , and errors were classified as major or minor based on criteria used in earlier studies . Results : Fifty-four of the 221 references had errors , for an overall error rate of 24.4 percent . Major errors were found in 21.3 percent of the references , and minor errors were calculated at 3.2 percent . Errors in the author ’s name were most common , followed by errors in titles of articles and books . The rates of reference errors in this study were lower than those reported previously in the nursing and medical literature The aim of the study was to investigate the reference and quotation accuracy in four peer- review ed manual therapy journals . A stratified r and om sample of original research ( n=7 ) was collected from each of the journals spanning the years January 2000 to December 2001 . A further r and om selection of 80 references from each journal paper sample d was then review ed ( Total N=320 ) for citation and quotation accuracy . Numbers of citations with errors were determined , then classified as either major or minor and categorized by bibliographic headings ( author , title , journal , year , volume , page and irretrievable ) . Each quotation was individually assessed for accuracy and judged to be either correct or incorrect . A quotation was deemed correct if it accurately substantiated and reported the original authors assertions . One hundred and fifteen citations across all journals contained errors ( 35.9 % ) . Some citations exhibited multiple major and minor errors . Bibliographically classified errors for all journals showed 61 author , 51 title , 6 journal , 4 year , 12 volume and 25 page errors . JMPT showed the lowest referencing error rate ( 20 % ) while JBWMT recorded the highest ( 58.8 % ) . The total number of quotation errors across all journals was 69 ( 12.3 % ) . JMPT showed the lowest quotation error rate of 6 ( 4.7 % ) , MT had 12 errors ( 7.3 % ) , JOM produced 21 errors ( 13.3 % ) , while JBWMT recorded the highest error rate with 32 ( 27.6 % ) . Poor citation and quotation is a reflection on the scholarly work of the authors and the journal . The trend for errors in quotation is more worrying than citation errors as it reflects poor diligence on the part of the investigators BACKGROUND Citation errors are common among nursing journals . But , there are no data regarding the factors that predispose to these errors . OBJECTIVE To determine the risk factors that predispose to citation error in peer- review ed nursing journals . METHODS Five hundred and fifty references were selected r and omly from articles published in eleven nursing journals for the year 1998 . The incidences of major and minor citation errors were determined by comparing with the original articles . The relative odds of citation errors for the number of authors , collaborating institutions and the length of the reference list were calculated . The correlation between the scientific quality of the journal ( by means of journal impact factor and immediacy index ) and the incidence of citation error were also determined . RESULTS The incidence of citation errors is comparable to those reported previously . Long reference lists in articles written by a single author predicted strongly the occurrence of minor citation errors . Journals with a high impact factor and immediacy index tend to contain fewer minor mistakes . None of these factors affect the incidence of major errors . CONCLUSION Contributors to journals should be aware of the various risk factors for citation errors . Citation accuracy may be improved by modifying these factors BACKGROUND Academic biomedical journals use peer review and editing to help to select and improve the quality of articles . We have investigated whether articles accepted by the Nederl and s Tijdschrift voor Geneeskunde , the Dutch Journal of Medicine , were improved after peer review and editing ( post-acceptance scientific and copy editing ) . METHODS 400 readers of the journal ( 100 each of medical students , recent medical graduates , general practitioners , and specialists ) were invited to participate in a question naire survey . The first 25 from each group who agreed to participate were included . We posted a pack containing a set of identically appearing typescripts ( ie , blinding ) of the su bmi tted , accepted , and published versions of 50 articles that had been published in Ned Tijdschr Geneeskd . Each evaluator received two of the sets of versions , and each set was evaluated by one person from each group . The package also included two question naires : the first was used to compare the su bmi tted with the accepted version ( 25 questions ) , the second compared the accepted with the published version ( 17 questions ) . The questions were answered on five-point scales , and were about the quality of the articles or were general/overall scores . We analysed the data as scores of 3 - 5 ( ie , improvement ) versus 1 - 2 . FINDINGS After peer review , the quality in 14 of 23 questions ( 61 % ) was significantly improved ( p = 0.03 or smaller ) . In particular , the overall score and general medical value were significantly improved ( p = 0.00001 for each ) . Editing led to significant improvement in 11 of 16 questions ( 69 % , p = 0.017 or smaller ) , and especially in style and readability ( p = 0.001 and p = 0.004 ) . Generally , we found no differences between the scores of the four categories of evaluators . 72 % of the evaluators correctly identified which version was which . INTERPRETATION Evaluations by readers of the Ned Tijdschr Geneeskd indicated significant improvement of published articles after both peer review and editing . We think that peer review and editing are worthwhile tasks . We also think that possible biases would have had a negligible effect on our results ( including the fact that we selected the first 25 evaluators who responded , that some evaluators may have read the published version , and that one question naire may have looked more scientific than the other , more editorial one ) We review ed all the references quoted in Volume 45(1990 ) ( n = 3967 ) and half the references quoted in Volume 49 ( 1994 ) ( n = 2183 ) of Anaesthesia . The references were numbered sequentially and 100 references from each year were r and omly selected . Citations of non‐journal articles were omitted leaving 197 citations for careful scrutiny . The authors ’ names , article title , journal title , volume number , page numbers , and year were examined in each selected reference . A reference was deemed correct if each element of the citation was identical to its source . Of the references examined , 32 % and 41 % contained one or more errors in 1990 and 1994 , respectively . The elements most likely to be inaccurate were , in descending order of frequency , article title , author , and page number . There was no significant difference in the error rate between the 2 years . It is the responsibility of contributors to ensure that all references are carefully checked From a systematic study of 500 references r and omly selected in the January through July , 1992 , issues of the Journal of Oral and Maxillofacial Surgery , it was found that 26 % had errors . 6.2 % of the referenced articles could not be found at all ; either due to the fact that they were obscure foreign articles , their age made it difficult to verify , they cited non-peer review ed journals , or the references cited journals that possibly did not exist . The remaining references were verified either from the original source or from other indexing tools if the original was not available OBJECTIVE To assess the accuracy of references in articles published in Emergency Medicine , and to categorize these errors . METHODS All the references in Volume 12 of Emergency Medicine were listed and numbered consecutively . A sample of 100 references was then selected . Each reference was then checked , initially on an electronic data base , with the original article being used as the gold st and ard . RESULTS 1469 citations were included in the study . A r and om sample of 100 was taken and examined in detail . 35 papers were shown to have at least one error , and a total of 41 errors were found . The maximum number of errors in one paper was 3 . These errors are analysed in detail . CONCLUSION Poor reference accuracy is a common problem in medical literature , and Emergency Medicine is not immune to these failings . Authors need to take more care to ensure that the accuracy of citations improves PURPOSE To investigate the frequency of citation and quotation errors in the ophthalmic literature . DESIGN Analysis of 200 references from 100 papers published in 10 ophthalmic journals . METHODS A sample of 20 references was r and omly selected from each of the 10 journals and each reference was checked for accuracy . Quotations were categorized as totally , partially , or not accurate . RESULTS There were 35 citation errors in 32 references , only four of which were errors in PubMed . Thirty quotations of references were not accurate ; 20 were partially accurate . CONCLUSIONS Citation and quotation errors are relatively common within the ophthalmic literature . This may be improved through technical editing RATIONALE AND OBJECTIVES The authors performed this study to determine the effect of routine editing on the style quality of trainee-generated radiology reports . MATERIAL S AND METHODS Trainee-generated reports of 50 body computed tomographic scans obtained at a tertiary care cancer center were edited in a routine fashion by one of two attending radiologists . Three physicians and four radiologists each independently evaluated the r and omized unedited and edited reports ( n = 100 ) and rated each report for clarity , brevity , readability , and quality of the impression by using a five-point scale . RESULTS Editing significantly improved mean ratings for clarity ( 4.6 after editing vs 4.2 before editing , P < .007 ) , brevity ( 4.6 vs 4.2 , P < .007 ) , readability ( 4.4 vs 4.1 , P < .007 ) , and quality of the impression ( 4.5 vs 4.3 , P < .007 ) . CONCLUSION Routine editing of trainee-generated reports significantly improves the perceived report quality . This finding suggests that greater emphasis should be placed on stylistic aspects of reporting during training to improve report style quality at dictation We verified a r and om sample of 50 references in the May 1986 issue of each of three public health journals . Thirty-one per cent of the 150 references had citation errors , one out of 10 being a major error ( reference not locatable ) . Thirty per cent of the references differed from authors ' use of them with half being a major error ( cited paper not related to author 's contention ) |
12,177 | 26,088,456 | The choice of an anti-EGFR MoAb as first-line biologic is a valid option in RAS wild-type patients c and i date to a doublet with infusional 5-FU . | BACKGROUND The use of anti-EGFR monoclonal antibodies ( MoAbs ) is restricted in Europe to RAS wild-type metastatic colorectal cancer ( mCRC ) patients .
While up today these targeted agents have been mainly chosen as salvage treatment in later lines , their use in first-line in combination with chemotherapy is highly debated . | BACKGROUND Patients with metastatic colorectal cancer that harbors KRAS mutations in exon 2 do not benefit from anti-epidermal growth factor receptor ( EGFR ) therapy . Other activating RAS mutations may also be negative predictive biomarkers for anti-EGFR therapy . METHODS In this prospect ive-retrospective analysis , we assessed the efficacy and safety of panitumumab plus oxaliplatin , fluorouracil , and leucovorin ( FOLFOX4 ) as compared with FOLFOX4 alone , according to RAS ( KRAS or NRAS ) or BRAF mutation status . A total of 639 patients who had metastatic colorectal cancer without KRAS mutations in exon 2 had results for at least one of the following : KRAS exon 3 or 4 ; NRAS exon 2 , 3 , or 4 ; or BRAF exon 15 . The overall rate of ascertainment of RAS status was 90 % . RESULTS Among 512 patients without RAS mutations , progression-free survival was 10.1 months with panitumumab-FOLFOX4 versus 7.9 months with FOLFOX4 alone ( hazard ratio for progression or death with combination therapy , 0.72 ; 95 % confidence interval [ CI ] , 0.58 to 0.90 ; P=0.004 ) . Overall survival was 26.0 months in the panitumumab-FOLFOX4 group versus 20.2 months in the FOLFOX4-alone group ( hazard ratio for death , 0.78 ; 95 % CI , 0.62 to 0.99 ; P=0.04 ) . A total of 108 patients ( 17 % ) with nonmutated KRAS exon 2 had other RAS mutations . These mutations were associated with inferior progression-free survival and overall survival with panitumumab-FOLFOX4 treatment , which was consistent with the findings in patients with KRAS mutations in exon 2 . BRAF mutations were a negative prognostic factor . No new safety signals were identified . CONCLUSIONS Additional RAS mutations predicted a lack of response in patients who received panitumumab-FOLFOX4 . In patients who had metastatic colorectal cancer without RAS mutations , improvements in overall survival were observed with panitumumab-FOLFOX4 therapy . ( Funded by Amgen and others ; PRIME Clinical Trials.gov number , NCT00364013 . ) BACKGROUND Cetuximab , an IgG1 chimeric monoclonal antibody against epidermal growth factor receptor ( EGFR ) , has activity against colorectal cancers that express EGFR . METHODS From December 2003 to August 2005 , 572 patients who had colorectal cancer expressing immunohistochemically detectable EGFR and who had been previously treated with a fluoropyrimidine , irinotecan , and oxaliplatin or had contraindications to treatment with these drugs underwent r and omization to an initial dose of 400 mg of cetuximab per square meter of body-surface area followed by a weekly infusion of 250 mg per square meter plus best supportive care ( 287 patients ) or best supportive care alone ( 285 patients ) . The primary end point was overall survival . RESULTS In comparison with best supportive care alone , cetuximab treatment was associated with a significant improvement in overall survival ( hazard ratio for death , 0.77 ; 95 % confidence interval [ CI ] , 0.64 to 0.92 ; P=0.005 ) and in progression-free survival ( hazard ratio for disease progression or death , 0.68 ; 95 % CI , 0.57 to 0.80 ; P<0.001 ) . These benefits were robust after adjustment in a multivariable Cox proportional-hazards model . The median overall survival was 6.1 months in the cetuximab group and 4.6 months in the group assigned to supportive care alone . Partial responses occurred in 23 patients ( 8.0 % ) in the cetuximab group but in none in the group assigned to supportive care alone ( P<0.001 ) ; the disease was stable in an additional 31.4 % of patients assigned to cetuximab and in 10.9 % of patients assigned to supportive care alone ( P<0.001 ) . Quality of life was better preserved in the cetuximab group , with less deterioration in physical function and global health status scores ( both P<0.05 ) . Cetuximab treatment was associated with a characteristic rash ; a rash of grade 2 or higher was strongly associated with improved survival ( hazard ratio for death , 0.33 ; 95 % CI , 0.22 to 0.50 ; P<0.001 ) . The incidence of any adverse event of grade 3 or higher was 78.5 % in the cetuximab group and 59.1 % in the group assigned to supportive care alone ( P<0.001 ) . CONCLUSIONS Cetuximab improves overall survival and progression-free survival and preserves quality -of-life measures in patients with colorectal cancer in whom other treatments have failed . ( Clinical Trials.gov number , NCT00079066 [ Clinical Trials.gov ] . ) Summary Background Therapeutic antibodies targeting EGFR have activity in advanced colorectal cancer , but results from clinical trials are inconsistent and the population in which most benefit is derived is uncertain . Our aim was to assess the addition of panitumumab to irinotecan in pretreated advanced colorectal cancer . Methods In this open-label , r and omised trial , we enrolled patients who had advanced colorectal cancer progressing after fluoropyrimidine treatment with or without oxaliplatin from 60 centres in the UK . From December , 2006 until June , 2008 , molecularly unselected patients were recruited to a three-arm design including irinotecan ( control ) , irinotecan plus ciclosporin , and irinotecan plus panitumumab ( IrPan ) groups . From June 10 , 2008 , in response to new data , the trial was amended to a prospect ively stratified design , restricting panitumumab r and omisation to patients with KRAS wild-type tumours ; the results of the comparison between the irinotcan and IrPan groups are reported here . We used a computer-generated r and omisation sequence ( stratified by previous EGFR targeted therapy and then minimised by centre , WHO performance status , previous oxaliplatin , previous bevacizumab , previous dose modifications , and best previous response ) to r and omly allocate patients to either irinotecan or IrPan . Patients in both groups received 350 mg/m2 intravenous irinotecan every 3 weeks ( 300 mg/m2 if aged ≥70 years or a performance status of 2 ) ; patients in the IrPan group also received intravenous panitumumab 9 mg/kg every 3 weeks . The primary endpoint was overall survival in KRAS wild-type patients who had not received previous EGFR targeted therapy , analysed by intention to treat . Tumour DNA was pyrosequenced for KRASc.146 , BRAF , NRAS , and PIK3CA mutations , and predefined molecular subgroups were analysed for interaction with the effect of panitumumab . This study is registered , number IS RCT N93248876 . Results Between Dec 4 , 2006 , and Aug 31 , 2010 , 1198 patients were enrolled , of whom 460 were included in the primary population of patients with KRASc.12–13,61 wild-type tumours and no previous EGFR targeted therapy . 230 patients were r and omly allocated to irinotecan and 230 to IrPan . There was no difference in overall survival between groups ( HR 1·01 , 95 % CI 0·83–1·23 ; p=0·91 ) , but individuals in the IrPan group had longer progression-free survival ( 0·78 , 0·64–0·95 ; p=0·015 ) and a greater number of responses ( 79 [ 34 % ] patients vs 27 [ 12 % ] ; p<0·0001 ) than did individuals in the irinotecan group . Grade 3 or worse diarrhoea ( 64 [ 29 % ] of 219 patients vs 39 [ 18 % ] of 218 patients ) , skin toxicity ( 41 [ 19 % ] vs none ) , lethargy ( 45 [21]% vs 24 [ 11 % ] ) , infection ( 42 [ 19 % ] vs 22 [ 10 % ] ) and haematological toxicity ( 48 [ 22 % ] vs 27 [ 12 % ] ) were reported more commonly in the IrPan group than in the irinotecan group . We recorded five treatment-related deaths , two in the IrPan group and three in the irinotecan group . Interpretation Adding panitumumab to irinotecan did not improve the overall survival of patients with wild-type KRAS tumours . Further refinement of molecular selection is needed for substantial benefits to be derived from EGFR targeting agents . Funding Cancer Research UK , Amgen |
12,178 | 32,103,644 | We found no significant changes from baseline in lung function , dyspnea , or exercise capacity .
Although PH-specific agents provided small health-related quality -of-life benefits , our meta- analysis provides insufficient evidence to support their use in IPF patients | BACKGROUND Pulmonary hypertension ( PH ) is common in patients with idiopathic pulmonary fibrosis ( IPF ) and is associated with poor outcomes .
This study was performed to determine the clinical efficacy of PH-specific therapeutic agents for IPF patients . | BACKGROUND Idiopathic pulmonary fibrosis ( IPF ) is a progressive lung disease with pulmonary vasculopathy . OBJECTIVE The purpose of this study was to determine whether sildenafil improves 6-min walk distance ( 6MWD ) in subjects with IPF and right ventricular dysfunction . METHODS The IPFnet , a network of IPF research centers in the United States , conducted a r and omized trial examining the effect of sildenafil on 6MWD in patients with advanced IPF , defined by carbon monoxide diffusing capacity < 35 % predicted . A sub study examined 119 of 180 r and omized subjects where echocardiograms were available for independent review by two cardiologists . Right ventricular ( RV ) hypertrophy ( RVH ) , right ventricular systolic dysfunction ( RVSD ) , and right ventricular systolic pressure ( RVSP ) were assessed . Multivariable linear regression models estimated the relationship between RV abnormality , sildenafil treatment , and changes in 6MWD , St. George 's Respiratory Question naire ( SGRQ ) , the EuroQol instrument , and SF-36 Health Survey ( SF-36 ) from enrollment to 12 weeks . RESULTS The prevalence of RVH and RVSD were 12.8 % and 18.6 % , respectively . RVSP was measurable in 71 of 119 ( 60 % ) subjects ; mean RVSP was 42.5 mm Hg . In the subgroup of subjects with RVSD , subjects treated with sildenafil experienced less decrement in 6MWD ( 99.3 m ; P = .01 ) and greater improvement in SGRQ ( 13.4 points ; P = .005 ) and EuroQol visual analog scores ( 17.9 points ; P = .04 ) than subjects receiving placebo . In the subgroup with RVH , sildenafil was not associated with change in 6MWD ( P = .13 ) , but was associated with greater relative improvement in SGRQ ( 14.8 points ; P = .02 ) vs subjects receiving placebo . Sildenafil treatment in those with RVSD and RVH was not associated with change in SF-36 . CONCLUSIONS Sildenafil treatment in IPF with RVSD results in better preservation of exercise capacity as compared with placebo . Sildenafil also improves quality of life in subjects with RVH and RVSD Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension . Aerosolized prostagl and in (PG)I2 caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mmHg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn.s.cm-5 ( p < 0.005 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left-shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn.s.cm-5 . In contrast , both intravenous PGI2 and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition PGI2 infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI2 analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI2 or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis RATIONALE A previous trial of bosentan in idiopathic pulmonary fibrosis ( IPF ) showed a trend to delayed IPF worsening or death . Also , improvements in some measures of dyspnea and health-related quality of life were observed . OBJECTIVES To demonstrate that bosentan delays IPF worsening or death . METHODS Prospect i ve , r and omized ( 2:1 ) , double-blind , placebo-controlled , event-driven , parallel-group , morbidity-mortality trial of bosentan in adults with IPF of less than 3 years ' duration , confirmed by surgical lung biopsy , and without extensive honeycombing on high-resolution computed tomography . The primary endpoint was time to IPF worsening ( a confirmed decrease from baseline in FVC ≥ 10 % and diffusing capacity of the lung for carbon monoxide ≥ 15 % , or acute exacerbation of IPF ) or death up to End of Study . Effects of bosentan on health-related quality of life , dyspnea , and the safety and tolerability of bosentan were investigated . MEASUREMENTS AND MAIN RESULTS Six hundred sixteen patients were r and omized to bosentan ( n=407 ) or placebo ( = 209 ) . No significant difference between treatment groups was observed in the primary endpoint analysis ( hazard ratio , 0.85 ; 95 % confidence interval , 0.66 - 1.10 ; P=0.2110 ) . No treatment effects were observed on health-related quality of life or dyspnea . Some effects of bosentan treatment were observed in changes from baseline to 1 year in FVC and diffusing capacity of the lung for carbon monoxide . The safety profile for bosentan was similar to that observed in other trials . CONCLUSIONS The primary objective in the Bosentan Use in Interstitial Lung Disease-3 trial was not met . Bosentan was well tolerated . Clinical trial registered with www . clinical trials.gov ( NCT 00391443 ) 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 aim of this study was to prospect ively evaluate the prevalence of pulmonary hypertension ( PH ) in patients with idiopathic pulmonary fibrosis ( IPF ) . One hundred thirty-nine patients ( 101 male , mean age = 68.6 ± 9 years ) , with confirmed IPF and who were admitted to eight Pulmonary Departments in Greece between November 2005 and December 2006 were included in the study . Pulmonary artery systolic pressure ( PASP ) was estimated by echocardiography , and PH was defined as PASP > 36 mmHg . We compared demographics , pulmonary function tests , NYHA functional status , 6-min walk distance ( 6MWD ) , B-type natriuretic peptide ( BNP ) , PaO2 , and P(A-a)O2 at rest data between patients with PH and without PH ( PASP ≤ 36 mmHg ) . Increased estimated right ventricular systolic pressure was present in 55 % of patients ( mean PASP = 47.1 ± 11.2 mmHg vs. 30.3 ± 3.8 mmHg , respectively ) . Patients with PH had a lower but not statistically significant DLCO ( 47.1 ± 18.8 vs. 52.5 ± 20.1 ) , lower PaO2 at rest ( 64.6 ± 12.2 vs. 71.1 ± 11.3 , P = 0.004 ) , and lower mean 6MWD ( 282 ± 118 vs. 338 ± 91 , P = 0.007 ) . Significant differences were also observed in the NYHA functional status between the two groups ( P = 0.02 ) . Statistically significant correlations were observed between PASP and PaO2 at rest ( r = −0.331 , P = 0.00 ) , P(A-a)O2 at rest ( r = 0.494 , P = 0.00 ) , 6MWD ( r = −0.264 , P = 0.01 ) , SpO2 at rest ( r = −0.293 , P = 0.00 ) , SpO2 at the end of exercise ( r = −0.364 , P = 0.00 ) , and also BNP values ( r = 0.319 , P = 0.01 ) . Moreover , PaO2 ( P = 0.02 ) , P(A-a)O2 ( P = 0.005 ) , and SpO2 at the end of exercise ( P = 0.023 ) were independent predictors of the presence of estimated PH . Using Doppler echocardiography as a screening tool for the estimation of PH , we found that PH is common in patients with IPF . Gas exchange parameters at rest and exercise desaturation might indicate underlying PH in IPF Idiopathic pulmonary fibrosis is a progressive , fatal disease . This prospect i ve , r and omised , double-blind , multicentre , parallel-group , placebo-controlled phase II trial ( NCT00903331 ) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis . Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy . The primary objective was to demonstrate that macitentan ( 10 mg once daily ) positively affected forced vital capacity versus placebo . Using a central ised system , 178 subjects were r and omised ( 2:1 ) to macitentan ( n=119 ) or placebo ( n=59 ) . The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm . Overall , no differences between treatments were observed in pulmonary function tests or time to disease worsening or death . Median exposures to macitentan and placebo were 14.5 months and 15.0 months , respectively . Alanine and /or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4 % of macitentan-treated subjects and 5.1 % of placebo recipients . In conclusion , the primary objective was not met . Long-term exposure to macitentan was well tolerated with a similar , low incidence of elevated hepatic aminotransferases in each treatment group . Long-term exposure to macitentan was well tolerated in IPF in a trial that did not meet its primary end-point Pulmonary hypertension is a life-threatening complication of lung fibrosis . Vasodilator therapy is difficult owing to systemic side effects and pulmonary ventilation-perfusion mismatch . We compared the effects of intravenous prostacyclin and inhaled NO and aerosolized prostacyclin in r and omized order and , in addition , tested for effects of oxygen and systemic calcium antagonists ( CAAs ) in eight patients with lung fibrosis and pulmonary hypertension . Aerosolized prostagl and in (PG)I(2 ) caused preferential pulmonary vasodilatation with a decrease in mean pulmonary arterial pressure from 44.1 + /- 4.2 to 31.6 + /- 3.1 mm Hg , and pulmonary vascular resistance ( RL ) from 810 + /- 226 to 386 + /- 69 dyn . s. cm(-)(5 ) ( p < 0.05 , respectively ) . Systemic arterial pressure , arterial oxygen saturation , and pulmonary right-to-left shunt flow , measured by multiple inert gas analysis , were not significantly changed . Inhaled NO similarly result ed in selective pulmonary vasodilatation , with RL decreasing from 726 + /- 217 to 458 + /- 81 dyn . s. cm(-)(5 ) . In contrast , both intravenous PGI(2 ) and CAAs were not pulmonary selective , result ing in a significant drop in arterial pressure . In addition , PGI(2 ) infusion caused a marked increase in shunt flow . Long-term therapy with aerosolized iloprost ( long-acting PGI(2 ) analog ) result ed in unequivocal clinical improvement from a state of immobilization and severe resting dyspnea in a patient with decompensated right heart failure . We concluded that , in pulmonary hypertension secondary to lung fibrosis , aerosolization of PGI(2 ) or iloprost causes marked pulmonary vasodilatation with maintenance of gas exchange and systemic arterial pressure . Long-term therapy with inhaled iloprost may be life saving in decompensated right heart failure from pulmonary hypertension secondary to lung fibrosis The clinical course of pulmonary hypertension ( PH ) in idiopathic pulmonary fibrosis ( IPF ) is not known except in advanced disease . 488 subjects in a placebo-controlled study of ambrisentan in IPF with mild – moderate restriction in lung volume , underwent right heart catheterisation ( RHC ) at baseline and 117 subjects ( 24 % ) had repeated haemodynamic measurements at 48 weeks . The subjects were categorised into a ) World Health Organization ( WHO ) Group 3 PH ( PH associated with pulmonary disease ) , n=68 ( 14 % ) ; b ) WHO Group 2 PH ( PH associated with left-sided cardiac disease ) , n=25 ( 5 % ) ; c ) no PH but elevated pulmonary artery wedge pressure ( PAWP ) , n=21 ( 4 % ) ; and d ) no PH but without elevation of PAWP , n=374 ( 77 % ) . The WHO Group 3 PH subjects had a lower diffusion capacity , 6MWD and oxygen saturation compared to the subjects with no PH . There was no significant change in mean pulmonary arterial pressure with ambrisenten or placebo after 12 months . Subjects with IPF associated with WHO Group 3 PH had impaired gas exchange and exercise capacity compared to patients without PH . An additional 9 % of the subjects had haemodynamic evidence of sub clinical left-ventricular dysfunction . Pulmonary artery pressures remained stable over 1 year in the majority of the cohort . In IPF associated with pulmonary hypertension ( PH ) , gas exchange is severely impaired ; the PH was stable over 1 year BACKGROUND Sildenafil , a phosphodiesterase-5 inhibitor , may preferentially improve blood flow to well-ventilated regions of the lung in patients with advanced idiopathic pulmonary fibrosis , which could result in improvements in gas exchange . We tested the hypothesis that treatment with sildenafil would improve walk distance , dyspnea , and quality of life in patients with advanced idiopathic pulmonary fibrosis , defined as a carbon monoxide diffusion capacity of less than 35 % of the predicted value . METHODS We conducted a double-blind , r and omized , placebo-controlled trial of sildenafil in two periods . The first period consisted of 12 weeks of a double-blind comparison between sildenafil and a placebo control . The primary outcome was the proportion of patients with an increase in the 6-minute walk distance of 20 % or more . Key secondary outcomes included changes in oxygenation , degree of dyspnea , and quality of life . The second period was a 12-week open-label evaluation involving all patients receiving sildenafil . RESULTS A total of 180 patients were enrolled in the study . The difference in the primary outcome was not significant , with 9 of 89 patients ( 10 % ) in the sildenafil group and 6 of 91 ( 7 % ) in the placebo group having an improvement of 20 % or more in the 6-minute walk distance ( P=0.39 ) . There were small but significant differences in arterial oxygenation , carbon monoxide diffusion capacity , degree of dyspnea , and quality of life favoring the sildenafil group . Serious adverse events were similar in the two study groups . CONCLUSIONS This study did not show a benefit for sildenafil for the primary outcome . The presence of some positive secondary outcomes creates clinical equipoise for further research . ( Funded by the National Heart , Lung , and Blood Institute and others ; Clinical Trials.gov number , NCT00517933 . BACKGROUND Idiopathic pulmonary fibrosis ( IPF ) is characterized by formation and proliferation of fibroblast foci . Endothelin-1 induces lung fibroblast proliferation and contractile activity via the endothelin A ( ETA ) receptor . OBJECTIVE To determine whether ambrisentan , an ETA receptor-selective antagonist , reduces the rate of IPF progression . DESIGN R and omized , double-blind , placebo-controlled , event-driven trial . ( Clinical Trials.gov : NCT00768300 ) . SETTING Academic and private hospitals . PARTICIPANTS Patients with IPF aged 40 to 80 years with minimal or no honeycombing on high-resolution computed tomography scans . INTERVENTION Ambrisentan , 10 mg/d , or placebo . MEASUREMENTS Time to disease progression , defined as death , respiratory hospitalization , or a categorical decrease in lung function . RESULTS The study was terminated after enrollment of 492 patients ( 75 % of intended enrollment ; mean duration of exposure to study medication , 34.7 weeks ) because an interim analysis indicated a low likelihood of showing efficacy for the end point by the scheduled end of the study . Ambrisentan-treated patients were more likely to meet the prespecified criteria for disease progression ( 90 [ 27.4 % ] vs. 28 [ 17.2 % ] patients ; P = 0.010 ; hazard ratio , 1.74 [ 95 % CI , 1.14 to 2.66 ] ) . Lung function decline was seen in 55 ( 16.7 % ) ambrisentan-treated patients and 19 ( 11.7 % ) placebo-treated patients ( P = 0.109 ) . Respiratory hospitalizations were seen in 44 ( 13.4 % ) and 9 ( 5.5 % ) patients in the ambrisentan and placebo groups , respectively ( P = 0.007 ) . Twenty-six ( 7.9 % ) patients who received ambrisentan and 6 ( 3.7 % ) who received placebo died ( P = 0.100 ) . Thirty-two ( 10 % ) ambrisentan-treated patients and 16 ( 10 % ) placebo-treated patients had pulmonary hypertension at baseline , and analysis stratified by the presence of pulmonary hypertension revealed similar results for the primary end point . LIMITATION The study was terminated early . CONCLUSION Ambrisentan was not effective in treating IPF and may be associated with an increased risk for disease progression and respiratory hospitalizations . PRIMARY FUNDING SOURCE Gilead Sciences BACKGROUND Lung fibrosis can be complicated by pulmonary hypertension , limiting exercise tolerance and life expectancy . Furthermore , vasodilators might cause deterioration in gas exchange . Our aim was to compare acute effects of sildenafil , nitric oxide , and epoprostenol in individuals with pulmonary hypertension secondary to lung fibrosis . METHODS We did a r and omised controlled , open-label trial , in 16 individuals admitted to our hospital with pulmonary hypertension secondary to lung fibrosis . After inhalation of nitric oxide ( 10 - 20 ppm ) , we assigned patients to either maximum tolerated dose of intravenous epoprostenol ( mean 8.0 ng/kg per min ; n=8 ) or oral sildenafil ( 50 mg ; n=8 ) . Our primary objective was to assess pulmonary vasodilative potency ( decrease in pulmonary vascular resistance index ) of sildenafil by comparison with inhaled nitric oxide and infused epoprostenol . Analyses were by intention to treat . FINDINGS Pulmonary vascular resistance index was reduced by nitric oxide ( -21.9 % , 95 % CI -14.1 to -36.2 ) , epoprostenol ( -36.9 % , -24.4 to -59.6 ) , and sildenafil ( -32.5 % , -10.2 to -54.1 ) . However , ratio of pulmonary to systemic vascular resistance decreased only in individuals who received nitric oxide and sildenafil . Baseline measurement of multiple-inert-gas elimination showed right-to-left shunt flow ( 4.8 % , 0.0 - 28.2 ) and little perfusion of low ventilation(V)/perfusion(Q ) areas ( 0.1 % , 0.0 - 13.0 ) . Prostacyclin increased V/Q mismatch ( shunt 16.8 % , 10.8 - 35.9 ; low V/Q 3.8 % , 0.0 - 13.0 ) and decreased arterial oxygenation . By contrast , nitric oxide ( 4.5 % , 0.0 - 18.0 ; 0.0 % , 0.0 - 17.3 ) and sildenafil ( 3.3 % , 0.0 - 11.3 ; 0.0 % , 0.0 - 12.4 ) maintained V/Q matching , with raised arterial partial pressure of oxygen ( 14.3 mm Hg , -1.7 to 31.3 ) noted for sildenafil . We recorded no adverse events . INTERPRETATION Sildenafil causes preferential pulmonary vasodilation and improves gas exchange in patients with severe lung fibrosis and secondary pulmonary hypertension STUDY OBJECTIVES To evaluate the long-term clinical course of patients with idiopathic pulmonary fibrosis ( IPF ) complicated with pulmonary arterial hypertension . DESIGN Prospect i ve analysis of consecutive IPF patients undergoing initial workup with right-heart catheterization ( RHC ) and pulmonary function testing ( PFT ) . Pulmonary arterial pressure ( PAP ) and diffusion capacity of the lung for carbon monoxide ( Dlco ) were focused on . SETTING University hospital . PATIENTS Seventy-eight patients with IPF ( 67 men , 11 women ; diagnosis by pathology , n = 59 ; clinical diagnosis , n = 19 ) had been followed up after initial workup for a maximum of 14 years . MEASUREMENTS AND RESULTS RHC data on 61 patients and PFT data on 52 patients were available . Five-year survival rates were 62.2 % in the normal-PAP group ( mean PAP < 17 mm Hg , n = 37 ) and 16.7 % in the high-PAP group ( mean PAP > 17 mm Hg , n = 24 ) [ p < 0.001 ] ; 70.4 % in the preserved-Dlco group ( percentage of predicted > 40 % , n = 27 ) and 20.0 % in the low-Dlco group ( percentage of predicted < 40 % , n = 25 ) [ p < 0.001 ] ; and 82.6 % in group 1 ( normal PAP and preserved Dlco , n = 23 ) and 15.6 % in group 2 ( high PAP , low Dlco , or both , n = 32 ) [ p < 0.0001 ] . The relative risks of mortality within 5 years after RHC were 2.20 ( 95 % confidence interval [ CI ] , 1.40 to 3.45 ) in the high-PAP group , 2.70 ( 95 % CI , 1.46 to 4.99 ) in the low-Dlco group , and 4.85 ( 95 % CI , 1.97 to 11.97 ) in group 2 . CONCLUSION Dlco was a critical factor for evaluating disease status and prognosis , and PAP status provided feasible information in the initial workup of IPF patients RATIONALE Idiopathic pulmonary fibrosis ( IPF ) is a progressive , fatal lung disease lacking effective treatment . OBJECTIVES To determine the effects of bosentan on exercise capacity and time to disease progression in patients with IPF . METHODS In a double-blind , multicenter trial , patients with IPF were r and omized to receive oral bosentan 62.5 mg twice daily for 4 weeks , increased to 125 mg twice daily thereafter , or placebo , for 12 months or longer . The primary efficacy endpoint was change from baseline up to Month 12 in exercise capacity , as measured by a modified six-minute-walk test . Secondary endpoints were time to death or disease progression ( worsening pulmonary function tests [ PFTs ] or acute decompensation ) , change in PFT scores , and quality of life ( QOL ) assessed using Short-Form 36 and St. George 's Respiratory Question naire . MEASUREMENTS AND MAIN RESULTS A total of 158 patients r and omly received bosentan ( n = 74 ) or placebo ( n = 84 ) . Bosentan showed no superiority over placebo in six-minute-walk distance ( 6MWD ) up to Month 12 , the primary efficacy endpoint . A trend in favor of bosentan was observed in the secondary endpoint of time to death or disease progression ( hazard ratio [ HR ] , 0.613 ; 95 % confidence interval [ CI ] , 0.328 - 1.144 ; P = 0.119 ) , which was more pronounced in a patient subgroup diagnosed using surgical lung biopsy ( post hoc analysis ; HR , 0.315 ; 95 % CI , 0.126 - 0.789 ; P = 0.009 ) . Changes from baseline up to Month 12 in assessment s of dyspnea and QOL favored treatment with bosentan . No unexpected adverse events were reported . CONCLUSIONS Bosentan treatment in patients with IPF did not show superiority over placebo on 6MWD . A trend in delayed time to death or disease progression , and improvement in QOL , was observed with bosentan . The more pronounced treatment effect in patients with biopsy-proven IPF warrants further investigation . Clinical trial registered with www . clinical trials.gov ( NCT 00071461 ) Idiopathic pulmonary fibrosis ( IPF ) is a form of idiopathic interstitial pneumonia characterized by temporally and spatially heterogeneous fibroblast proliferation and poor prognosis . No therapies have been shown in r and omized clinical trials ( RCT ) to influence survival . Twenty-nine subjects were assigned r and omly in a pilot study to a double-blind , placebo-controlled , RCT to test sildenafil in patients with IPF with forced vital capacity 40–90 % and diffusing capacity 30–90 % of predicted . During the 6-month experimental treatment period , patients underwent 6-min walk tests and estimation of dyspnea using the Borg scale at baseline ( 0 months ) , 3 months , and 6 months . Participants had moderate impairment of pulmonary function , and there were no significant differences between placebo ( n = 15 ) and sildenafil ( n = 14)-treated groups . Sildenafil did not significantly increase 6-min walk test distance ( mean distance ± SD after 6-month protocol : placebo 355 ± 82 m , sildenafil 324 ± 41 m ; p = 0.256 ) nor did it lessen dyspnea after exercise ( mean Borg score after 6-month protocol : placebo 3.4 ± 1.6 , sildenafil 4.1 ± 2.3 ; p = 0.492 ) . Adverse reactions were few and minor in nature . In this trial , sildenafil did not significantly increase 6-min walk test distance or decrease the Borg dyspnea index in patients with clinical ly typical IPF . This trial was registered at clinical trials.gov as NCT00359736 BACKGROUND Sildenafil offers potential to treat patients with pulmonary hypertension by selectively inhibiting phosphodiesterase type five pathways in the lung . It is recommended for selected patients with pulmonary arterial hypertension , but its role in the management of pulmonary hypertension associated with parenchymal lung disease is unclear . PATIENTS AND METHODS Seven patients ( 68 - 86 years ) with end stage chronic obstructive pulmonary disease ( COPD , 4 ) and idiopathic pulmonary fibrosis ( IPF , 3 ) were referred to our unit . All patients had a long-term history of chronic lung disease and were on maximal appropriate therapy prescribed by their referring pulmonologist . Thromboembolic disease was excluded by pulmonary angiography and all patients had had high resolution thoracic CT scan . At assessment right heart catheterisation , 2D echocardiography and 6-min walk test were performed prior to commencement of sildenafil 50 mg tds . Their medication was otherwise unchanged . After 8 weeks treatment , right heart catheterisation , 2D echocardiography and 6-min walk test were repeated . RESULTS The pulmonary vascular resistance was reduced in six patients ( from 13 , 3 , 3 , 6.5 , 3.5 and 10.5 wood units to 9.7 , 2.5 , 2.8 , 4.4 , 2.5 and 5.4 wood units , respectively ) . Six-minute walk test increased in six patients ( from 110 m , 210 m , 80 m , 30 m , 210 m and 80 m to 130 m , 312 m , 120 m , 82 m , 244 m and 100 m , respectively ) . One patient with COPD did not demonstrate a favourable response although their cardiac output increased on sildenafil therapy . 2D echocardiography showed a reduction in estimated PA pressure in six patients with an improvement in right ventricular systolic function in two COPD patients . CONCLUSION Our results suggest that sildenafil may have a role for selected patients with COPD and IPF who have pulmonary hypertension Background No drugs have been approved for the treatment of patients with pulmonary hypertension ( PH ) secondary to idiopathic pulmonary fibrosis ( IPF ) , particularly those with idiopathic honeycomb lung . This study was conducted to investigate the long-term efficacy and safety of bosentan for PH based on changes in prognosis and respiratory failure . Methods IPF patients with borderline or less severe PH and completely organized honeycomb lung were r and omized ( 1:1 ) to bosentan or no treatment for PH for 2 years and assessed at baseline and every 6 months for respiratory failure , activities of daily living ( ADL ) , lung and heart functions by right cardiac catheterization , and other parameters . An interim analysis was performed , however , following detection of a significant survival benefit favoring bosentan therapy . Results Significant differences were noted for the bosentan-treated ( n = 12 ) vs. untreated ( n = 12 ) groups in hospital-free survival ( 603.44 ± 50.074 days vs. 358.87 ± 68.65 days ; hazard ratio [ HR ] , 0.19 ; P = 0.017 ) and overall survival ( 671 days vs. 433.78 ± 66.98 days ; HR , 0.10 ; P = 0.0082 ) . Again , significant improvements were noted for the bosentan-treated group from baseline to month 6 or 12 in several indices in ADL , pulmonary circulation , and % DLCO . Without requiring O2 inhalation , bosentan was associated with no increase but a trend toward a decrease in adverse events and an improvement in respiratory status . Conclusions Bosentan tended to improve prognosis and ADL without worsening respiratory failure in IPF patients with borderline or less severe PH and completely organized honeycomb lung alone . Trial registration This study was registered on December 18 , 2010 with UMIN-CTR Clinical Trial as UMIN000004749 to investigate the long-term influence of bosentan on cardiac function , as well as its cardioprotective efficacy and safety , in patients with pulmonary hypertension secondary to concurrent COPD and IPF , respectively BACKGROUND Dyspnea and functional limitation in interstitial lung diseases ( ILD ) are not always adequately explained by the degree of compromise in pulmonary function alone . Pulmonary hypertension ( PH ) is felt to be a major contributor to morbidity and mortality in these patients . It is not clear whether treatment with newer vaso-active agents benefits patients with PH in the setting of moderate or severe ILD . METHODS Medical records of patients followed at our institution between July 2001 and June 2005 were review ed to identify patients with moderate or severe fibrotic ILD and PH . Data regarding demographics , hemodynamics , and clinical characteristics at baseline and during follow-up were collected . RESULTS We identified 19 patients who met our inclusion criteria and in whom vaso-active therapy [ epoprostenol ( N=10 ) , bosentan ( N=9 ) ] was initiated . Most patients [ ( 15/19(79 % ) ] showed an initial positive response to therapy and improved their 6-min walk distance ( 6MWD ) by > 50 m ( responders ) and 12/15 ( 80 % ) improved by at least 1 WHO functional class . At 1-year follow-up , 7 of 15 ( 47 % ) ' responders ' had deteriorated significantly . None of the patients died during 1 year of follow-up . CONCLUSIONS Epoprostenol and bosentan produced short-term functional benefit in our patients with PH and moderate or severe restrictive ILD . The generalizability of these results awaits the results of larger , prospect i ve , r and omized trials in such patients Background Nintedanib is an approved treatment for idiopathic pulmonary fibrosis ( IPF ) . A subgroup analysis of a previously published trial suggested that sildenafil may provide benefits regarding oxygenation , gas exchange as measured by the diffusion capacity of the lungs for carbon monoxide ( DlCO ) , symptoms , and quality of life in patients with IPF and severely decreased DlCO . That idea was tested in this trial . Methods We r and omly assigned , in a 1:1 ratio , patients with IPF and a DlCO of 35 % or less of the predicted value to receive nintedanib at a dose of 150 mg twice daily plus sildenafil at a dose of 20 mg three times daily ( nintedanib‐plus‐sildenafil group ) or nintedanib at a dose of 150 mg twice daily plus placebo three times daily ( nintedanib group ) for 24 weeks . The primary end point was the change from baseline in the total score on the St. George 's Respiratory Question naire ( SGRQ ) at week 12 ( the total score ranges from 0 to 100 , with higher scores indicating worse health‐related quality of life ) . Secondary end points included measures of dyspnea and safety . Results A total of 274 patients underwent r and omization . There was no significant difference in the adjusted mean change from baseline in the SGRQ total score at week 12 between the nintedanib‐plus‐sildenafil group and the nintedanib group ( ‐1.28 points and ‐0.77 points , respectively ; P=0.72 ) . A benefit from sildenafil treatment was not observed with regard to dyspnea as measured with the use of the University of California , San Diego , Shortness of Breath Question naire . No new safety signals were observed , as compared with previous trials . Conclusions In patients with IPF and a DlCO of 35 % or less of the predicted value , nintedanib plus sildenafil did not provide a significant benefit as compared with nintedanib alone . No new safety signals were identified with either treatment regimen in this population of patients . ( Funded by Boehringer Ingelheim ; INSTAGE Clinical Trials.gov number , NCT02802345 . RATIONALE FVC has emerged as a st and ard primary endpoint in clinical trials evaluating novel therapies for patients with idiopathic pulmonary fibrosis ( IPF ) . However , it has recently been proposed that all-cause mortality or a composite comprised of all-cause mortality and all-cause nonelective hospitalization be adopted as the st and ard primary endpoint for IPF clinical trials . OBJECTIVES To conduct a comprehensive evaluation of mortality in three phase 3 clinical trials and evaluate the feasibility of mortality trials in patients with IPF . METHODS The study population included 622 patients r and omized to placebo in the CAPACITY studies evaluating pirfenidone ( n = 347 ) or the INSPIRE study evaluating interferon-γ1b ( n = 275 ) . The Kaplan-Meier estimate of 2-year survival was fit to the exponential distribution and used to calculate sample size requirements for a mortality study with 90 % power to detect a 25 % reduction in all-cause mortality with a two-sided α of 0.05 . Modeling analyses were used to assess the effects of selected variables on sample size and study design . MEASUREMENTS AND MAIN RESULTS A total of 73 deaths occurred during the period of observation ( mean duration of follow-up , 80.1 wk ) . The all-cause mortality rate was 6.6 % at 1 year and 13.7 % at 2 years . Based on the observed 2-year mortality rate , a total of 508 events would be required to detect a significant treatment benefit in a two-arm trial with 90 % power to detect a 25 % reduction in all-cause mortality . The estimated sample size for a trial enrolled over 3 years with a maximum follow-up period of 5 years is 2,582 patients . CONCLUSIONS The all-cause mortality rate is relatively low in patients with IPF with mild to moderate impairment in lung function . Accordingly , the necessary size , duration , and cost of all-cause mortality trials in this population are substantial and likely prohibitive RATIONALE Pulmonary hypertension ( PH ) associated with fibrotic idiopathic interstitial pneumonia ( IIP ; idiopathic pulmonary fibrosis and nonspecific interstitial pneumonia ) confers important additional morbidity and mortality . OBJECTIVES To evaluate the safety and clinical efficacy of the dual endothelin-1 receptor antagonist bosentan in this patient group . METHODS In a r and omized , double-blind , placebo-controlled study , 60 patients with fibrotic IIP and right heart catheter confirmed PH were r and omized 2:1 to bosentan ( n = 40 ) or placebo ( n = 20 ) . The primary study endpoint was a fall from baseline pulmonary vascular resistance index ( PVRi ) of 20 % or more over 16 weeks . MEASUREMENTS AND MAIN RESULTS Sixty patients ( 42 men ; mean age , 66.6 ± 9.2 yr ) , with a mean pulmonary artery pressure of 36.0 ( ± 8.9 ) mm Hg , PVRi 13.0 ( ± 6.7 ) Wood Units/m(2 ) and reduced cardiac index of 2.21 ( ± 0.5 ) L/min/m(2 ) were recruited to the study . Accounting for deaths and withdrawals , paired right heart catheter data were available for analysis in 39 patients ( bosentan = 25 , placebo = 14 ) . No difference in the primary outcome was detected , with seven ( 28.0 % ) patients receiving bosentan , and four ( 28.6 % ) receiving placebo achieving a reduction in PVRi of greater than or equal to 20 % ( P = 0.97 ) at 16 weeks . There was no change in functional capacity or symptoms between the two groups at 16 weeks , nor any difference in rates of serious adverse events or deaths ( three deaths in each group ) . CONCLUSIONS This study shows no difference in invasive pulmonary hemodynamics , functional capacity , or symptoms between the bosentan and placebo groups over 16 weeks . Our data do not support the use of the dual endothelin-1 receptor antagonist , bosentan , in patients with PH and fibrotic IIP . Clinical trial registered with www . clinical trials.gov ( NCT 00637065 ) |
12,179 | 24,330,771 | In this systematic review , we present information relating to the effectiveness and safety of the following interventions : antibiotics ( oral , parenteral , different duration s , different regimens ) and routine antibiotic prophylaxis ( before intrauterine device insertion in women at high risk or low risk ) | INTRODUCTION Pelvic inflammatory disease is caused by infection of the upper female genital tract and is often asymptomatic .
Pelvic inflammatory disease is the most common gynaecological reason for admission to hospital in the US , and is diagnosed in approximately 1 % of women aged 16 to 45 years consulting their GP in Engl and and Wales .
METHODS AND OUTCOMES We conducted a systematic review and aim ed to answer the following clinical questions : How do different antimicrobial regimens compare when treating women with confirmed pelvic inflammatory disease ?
What are the effects of routine antibiotic prophylaxis to prevent pelvic inflammatory disease before intrauterine contraceptive device ( IUD ) insertion ? | This multicenter , prospect i ve , double-blind study compared the safety and efficacy of clindamycin and ciprofloxacin versus ceftriaxone and doxycycline in the treatment of out patients with mild to moderate pelvic inflammatory disease ( PID ) diagnosed by laparoscopy . Sample s taken from the endocervix , endometrium , and abdominal cavity before treatment and from the endocervix after treatment were cultured for aerobes , anaerobes , Neisseria gonorrhoeae , and Chlamydia trachomatis . Of the 138 patients enrolled , 131 were evaluable for efficacy . The most prevalent bacteria were streptococci , staphylococci , and Escherichia coli ( among aerobes ) and Bacteroides species and peptostreptococci ( among anaerobes ) . N. gonorrhoeae was present in 2 % ( 3 ) of the 131 evaluable patients , and C. trachomatis was in 11 % ( 15 ) . The clinical cure rate was 97 % ( 65 of 67 ) in the clindamycin and ciprofloxacin group and 95 % ( 61 of 64 ) in the ceftriaxone and doxycycline group . Side effects were similar in both groups . In conclusion , the two regimens for the outpatient treatment of mild to moderate PID were similarly effective and safe Eighty-two patients with laparoscopically confirmed salpingitis were r and omly divided into two groups in a multicentre and prospect i ve trial . Single drug therapy with the amoxicillin-clavulanic acid combination was used in 42 patients ( group A ) . The other 40 patients were given a combination of penicillin , aminoside and metronidazole ( group B ) . For each case a secondary prescription for a tetracycline was discussed . Clinical results were comparable in both groups : sooner ( at the end of the hospitalization period ) in group A : 10 cured , 30 improved and 2 failures against 9 cured , 30 improved in group B. Later ( evaluation after 5 to 8 weeks ) a relapse was noted in five patients in group A and included one case of angioedema in group B. It is concluded that amoxicillin-clavulanic acid combination is a satisfactory alternative to the penicillin-aminoside-metronidazole combination , especially as it is simpler to use Objective : This multinational , multicentre , prospect i ve , r and omised , double blind , parallel group , non-inferiority study compared the efficacy and safety of moxifloxacin monotherapy with ofloxacin plus metronidazole in women with uncomplicated pelvic inflammatory disease . Methods : Women from hospitals throughout 13 countries received a 14 day course of either oral moxifloxacin , 400 mg once daily ( n = 384 ) , or oral ofloxacin , 400 mg twice daily plus oral metronidazole , 500 mg twice daily ( n = 365 ) . Results : Of the 741 patients in the intent to treat ( ITT ) population , 564 ( 74.2 % ) were valid for the per protocol ( PP ) analyses ; 112 ( 19.9 % ) of these were included in the microbiologically valid population ( MBV ) . Clinical resolution rates in the PP population at the test of cure visit ( TOC , 5–24 days post-therapy , primary efficacy end point ) were 90.2 % ( 248/275 ) for moxifloxacin and 90.7 % ( 262/289 ) for ofloxacin plus metronidazole ( 95 % CI : −5.7 % to 4.0 % ) . At follow up ( 28–42 days post-therapy ) , resolution rates in the PP population were 85.8 % ( 236/275 ) and 87.9 % ( 254/289 ) for moxifloxacin and comparator , respectively ( 95 % CI : −8.0 % to 3.1 % ) . Bacteriological success rates in the MBV population at TOC were 87.5 % ( 49/56 ) for moxifloxacin and 82.1 % ( 46/56 ) for comparator ( 95 % CI : −8.3 % to 18.8 % ) . Against Chlamydia trachomatis and Neisseria gonorrhoeae , bacteriological success rates with moxifloxacin were 88.5 % ( 23/26 ) and 100 % ( 13/13 ) and for comparator 85.7 % ( 18/21 ) and 81.8 % ( 18/22 ) , respectively . Drug related adverse events occurred less frequently with moxifloxacin ( 22.5 % ( 85/378 ) ) versus the comparator ( 30.9 % ( 112/363 ) ) ( p = 0.01 ) . Conclusion : In uncomplicated PID , once daily moxifloxacin monotherapy was clinical ly and bacteriologically as efficacious as twice daily ofloxacin plus metronidazole therapy and was associated with fewer drug related adverse events Sixty patients with acute uncomplicated pelvic infection were treated with cefoxitin or ampicillin alone , the purpose being to show that a relatively cheap antimicrobial agent ( ampicillin ) could be used . The groups ( 30 patients in each ) were clinical ly comparable ( P greater than 0,01 - -Hotelling T-square test ) . In the first group 2 g ampicillin was administered intravenously on admission followed by 1 g intravenously 4-hourly , and in the second group 2 g cefoxitin was administered intravenously on admission followed by 1 g intravenously every 8 hours . A good response was obtained in both groups . On the basis of cost ampicillin would seem to be the treatment of choice in uncomplicated acute pelvic infection A prospect i ve , r and omized , controlled , non-blind clinical trial was conducted to compare the efficacy of monotherapy with ciprofloxacin with that of a combination of clindamycin plus gentamicin in the treatment of patients with acute pelvic inflammatory disease . Pretreatment and post-treatment cervical culture specimens were obtained for Neisseria gonorrhoeae , Chlamydia trachomatis , Mycoplasma hominis , and Ureaplasma urealyticum . Pretreatment and post-treatment endometrial culture specimens were obtained for those organisms plus facultative and anaerobic bacteria . Minimal inhibitory concentrations were determined on all isolates by agar dilution . Clinical resolution of infection was seen in 31 of 33 ( 94 percent ) ciprofloxacin-treated patients compared with 34 of 35 ( 97 percent ) clindamycin/gentamicin-treated patients . N. gonorrhoeae was eradicated in all cases and C. trachomatis in 12 of 13 cases ( 92 percent ) . Ciprofloxacin appeared less effective than clindamycin/gentamicin in eradicating bacterial-vaginosis-associated organisms from post-treatment culture specimens obtained from the endometrium . Comparable clinical response was seen with both regimens . The significance of persistent bacterial-vaginosis-associated organisms following ciprofloxacin therapy is unclear . However , since one goal of treatment of pelvic inflammatory disease should be to eliminate organisms from the upper genital tract , ciprofloxacin may not provide optimal single-agent therapy for pelvic inflammatory disease In this prospect i ve trial , 130 hospitalized patients with acute pelvic inflammatory disease based on clinical criteria were r and omly treated with intravenous gentamicin plus clindamycin ( N=63 ) or cefoxitin plus doxycycline ( N=67 ) for at least 4 days , followed by oral clindamycin or doxycycline , respectively , for a total of 14 days . Pre-treatment cultures were obtained for endocervical Neisseria gonorrhoeae and Chlamydia trachomatis , and for endometrial C trachomatis and aerobic and anaerobic bacteria . Overall , 46 subjects ( 35 % ) had endocervical cultures positive for N gonorrhoeae . Endocervical and endometrial cultures were positive for C trachomatis in 16 and 6 % , respectively . Ninety-five percent of patients had at least one aerobic bacterium , 38 % had at least one anaerobic bacterium , and only 2 % had no organisms isolated from their endometrium . Fifty-seven subjects taking gentamicin-clindamycin ( 90.5 % ) and 64 subjects taking cefoxitin-doxycycline ( 95.5 % ) were clinical ly cured , a nonsignificant difference . Three subjects treated with gentamicin- clindamycin and one treated with cefoxitindoxycycline required hysterectomy or salpingectomy for cure . Follow-up examinations and cultures were performed in 84 % of the subjects . Post-treatment cultures for N gonorrhoeae were negative in all cases tested . Post-treatment endocervical and endometrial C trachomatis cultures were negative in ten of 11 subjects treated with gentamicinclindamycin and in eight of nine treated with cefoxitindoxycycline , a nonsignificant difference . We conclude that gentamicin-clindamycin and cefoxitin-doxycycline have similar clinical cure rates for acute pelvic inflammatory disease and are equivalent in eradicating genital N gonorrhoeae and C A prospect i ve , r and omized study of intravenous followed by oral ciprofloxacin compared with the combination of intravenous clindamycin and gentamicin was conducted in 122 women hospitalized with pelvic infections . Clinical diagnoses included endometritis ( 97 patients ) and uncomplicated pelvic inflammatory disease ( 25 patients ) . Treatment successes for endometritis included 42 of 50 ( 84 percent ) patients treated with ciprofloxacin compared with 35 of 47 ( 75 percent ) treated with the clindamycin-gentamicin combination . Treatment successes for acute salpingitis included 10 of 10 ( 100 percent ) treated with ciprofloxacin and 13 of 15 ( 87 percent ) treated with clindamycin-gentamicin . Ciprofloxacin successfully eradicated Chlamydia trachomatis in 11 of 12 patients as did clindamycin-gentamicin in six of seven patients . In this study of pelvic infection , ciprofloxacin demonstrated efficacy comparable with the combination of clindamycin and gentamicin , and is effective against C. trachomatis Sixty-two women were r and omized in a double-blind fashion to receive one of two antibiotic regimens for the treatment of clinical ly diagnosed pelvic inflammatory disease . Thirty of .31 patients ( 96.8 % ) receiving a combination of cefoxitin with doxycycline and 28 of 31 ( 90.3 % ) receiving a combination of clindamycin with amikacin responded to therapy ( P = not significant ) . Chlamydia trachomatis , Neisseria gonorrhoea , or both were isolated from 13.3 , 7.0 , and 4.8 % of patients , respectively . Of the four patients not responding to therapy , all had inflammatory complexes . Cefoxitin/doxycycline and clindamycin/amikacin are both effective in the treatment of pelvic inflammatory disease This six-center , prospect i ve , open-label clinical trial compared the efficacy and safety of three regimens recommended by the Centers for Disease Control and Prevention ( CDC ) for the treatment of women hospitalized for acute pelvic inflammatory disease ( PID ) . The study focused on the response to inpatient therapy , not on long-term prevention of sequelae . A severity score was used for objective comparison of the degree of illness before and after therapy . Women were r and omly assigned ( in a 1:1:1 ratio ) to treatment with cefoxitin plus doxycycline , clindamycin plus gentamicin , or cefotetan plus doxycycline . Two hundred seventy-five ( 94.2 % ) of 292 evaluable women required no alteration in therapeutic regimen . The three regimens produced almost identical cure rates . No serious adverse clinical or laboratory events were observed . In short , the three regimens recommended by the CDC for inpatient therapy of acute PID were similarly effective and safe The vaginal douching habits of 100 consecutive municipal hospital patients with verified pelvic inflammatory disease ( cases ) were compared with those of 762 r and omly selected controls ( r and om controls ) and 119 women thought to have pelvic inflammatory disease but in whom the diagnosis was not confirmed by laparoscopy and /or endometrial biopsy specimen ( internal controls ) . Because patients had been symptomatic for no more than 3 weeks , current douching was arbitrarily defined as any douching during the previous 2 months . Current douching was more common among those with pelvic inflammatory disease than among r and om controls or internal controls . Among current douchers , pelvic inflammatory disease was significantly related to frequency of douching . For example , when cases were compared with r and om controls , those who douched three or more times per month were 3.6 times more likely than those who douched less than once per month to have confirmed pelvic inflammatory disease . A logistic regression model was used to adjust for demographic , behavioral , and other possible confounding variables . Even after adjustments , douching during the previous 2 months remained associated with pelvic inflammatory disease . These data suggest that among these women vaginal douching may be a risk factor for pelvic inflammatory disease We conducted a multicenter trial to compare the efficacy and safety of meropenem with the efficacy and safety of clindamycin plus gentamicin in the treatment of 515 hospitalized patients with acute gynecologic and obstetric pelvic infections . At the end of treatment , the rates of satisfactory clinical and bacteriologic response were high ( 88 % ) in both treatment groups : the rates of response were 90 % for the meropenem group and 86 % for the clindamycin/gentamicin group . No serious adverse events occurred . The most frequently reported drug-related adverse clinical events in the meropenem group were nausea and injection-site reactions ( > 1 % of patients ) , and the most common drug-related laboratory abnormality was thrombocythemia . Similar patterns of adverse events occurred in the clindamycin/gentamicin group ; however , the incidence of diarrhea and eosinophilia was higher in this group . In summary , this trial demonstrated that meropenem is an effective and safe alternative to the combination of clindamycin plus gentamicin for the treatment of women with acute gynecologic and obstetric pelvic infections Forty-four patients with severe pelvic inflammatory disease were r and omly divided into two groups . Single drug therapy with the amoxicillin-clavulanic acid was used in 22 patients ( group A ) . The other 22 patients ( group B ) were given a combination of ampicillin , gentamicin and metronidazole . Clinical results were comparable in both groups with 91 % successes and 9 % improvements in group A , against 86 % successes , 9 % failures , and 5 % non-interpretable results in group B. The difference between the two groups was not statistically significant ( p = 11.6 % ) . 30 % of patients in each group had positive serologic tests for Chlamydiae . This had no influence on therapeutic results but led to secondary prescription of a cycline . Because amoxicillin-clavulanic acid is active against aerobic and anaerobic pathogens , including beta-lactamase-producing microorganisms , it is a satisfactory alternative to the ampicillin-gentamicin-metronidazole combination , especially as it is simpler to use , less toxic and less expensive A multicenter r and omized comparative trial was done to assess the safety and efficacy of oral ofloxacin ( 400 mg twice daily for 10 days ) versus cefoxitin ( 2 g intramuscularly ) followed by doxycycline ( 100 mg twice daily orally for 10 days ) for the outpatient treatment of uncomplicated pelvic inflammatory disease ( PID ) . Neisseria gonorrhoeae ( GC ) grew on pretreatment endocervical cultures from 43 of 268 women ( 16 % ) , and in 30 of 247 women ( 12 % ) cultures were positive for Chlamydia trachomatis ( Ct ) . Ninety-five percent ( 122/128 ) of the women treated with the ofloxacin regimen and 93 % ( 112/121 ) of those treated with the cefoxitin/doxycycline regimen had cure or improvement on examination at a minimum of one follow-up visit . All GC species were eradicated by both ofloxacin and cefoxitin . Among women who returned for follow-up , the eradication of C trachomatis was 88 % ( 15/17 ) for the cefoxitin/doxycycline group and 100 % ( 18/18 ) for ofloxacin . Side effects were more prevalent in the cefoxitin/doxycycline group ( 15 % ) than in the ofloxacin group ( 7 % ) , nausea/vomiting being the most frequent adverse effect . In this study , it appears that ofloxacin and cefoxitin/doxycycline have similar clinical effectiveness for the outpatient treatment of uncomplicated pelvic inflammatory disease Patients with uncomplicated pelvic inflammatory disease ( PID ) ( acute salpingitis and no pelvic masses ) were r and omly assigned for treatment with either cefotaxime or cefoxitin . A clinical cure was achieved in 17 of 20 cases ( 82 % ) and 19 of 22 cases ( 84 % ) , respectively . Within the complicated PID group , patients were assigned to two subgroups : those with a tubo-ovarian complex ( 26 patients ) , and those with a tubo-ovarian abscess ( 32 patients ) , as confirmed by ultrasonography or surgery . Patients within each of these two subgroups were then r and omly assigned for treatment with either cefotaxime or clindamycin plus gentamicin . Within the tubo-ovarian complex subgroup , a clinical cure was achieved in 11 of 13 cases ( 85 % ) treated with cefotaxime and 10 of 13 cases ( 77 % ) treated with clindamycin plus gentamicin . Within the tubo-ovarian abscess subgroup , a clinical cure was achieved in 12 of 16 cases ( 75 % ) treated with cefotaxime and 11 of 16 cases ( 69 % ) treated with clindamycin plus gentamicin . No differences in any category were statistically significant . Specimens for culture were obtained from the endocervix , endometrium , and when possible , the cul-de-sac , fallopian tubes , and abscess . Neisseria gonorrhoeae ( 33 % ) was isolated more frequently than Chlamydia trachomatis ( 12 % ) in patients with PID , and neither of these organisms was isolated with any increased frequency in patients with complicated PID . The majority of the patients were considered to have polymicrobial infection . Cefotaxime was as efficacious as cefoxitin and clindamycin plus gentamicin for the treatment of acute salpingitis , tubo-ovarian complex and tubo-ovarian abscess A multicenter , prospect i ve , open-label , r and omized trial compared imipenem-cilastatin ( I-C ) monotherapy with the combination of clindamycin+gentamicin ( C+G ) . Efficacy and tolerability in the treatment of serious pelvic infections were evaluated in 94 female patients with acute salpingitis , pelvic abscess , or postoperative pelvic cellulitis . Duration of therapy averaged 5.4 days for treatment successes and ten days for treatment failures . The overall treatment success rate was 98 % ( 43 of 44 patients ) in the I-C group , compared with 92 % ( 46 of 50 patients ) in the C+G group ( P = NS ) . Adjunct therapy for two treatment successes in the I-C group included laparoscopy and surgical removal of a pelvic abscess without change in antibiotics . Both I-C and C+G were highly effective and generally well tolerated for the treatment of salpingitis , pelvic abscess , and postoperative pelvic cellulitis In a r and omised , double-blind , 3-way cross-over trial , the incidence of nausea associated with 2 doxycycline 100 mg formulations ( Doryx ' and Vibramycin ' ) were compared . The original study cohort comprised 103 healthy male volunteers , with 97 subjects completing the trial . Subjects were r and omly allocated to 1 of 3 treatment sequences and received a single dose of Doryx ' , Vibramycin ' or placebo , with a 7-day washout prior to cross-over . At half-hourly intervals , from 0 to 2 h post-dose , subjects completed question naires to indicate if they felt nauseous . Data were analysed according to a log-linear method for the analysis of cross-over trials with categorical responses . Seventeen , 29 and 11 subjects experienced nausea with Doryx ' , Vibramycin ' and placebo , respectively . A significantly greater number of volunteers indicated a positive response with Vibramycin ' vs Doryx ' and vs placebo ; the positive response frequency was not significantly different for the Doryx ' vs the placebo regimen . Treatment sequence had no significant effect on response , although a marked first-dose effect was noted ; the first ( vs the second and vs the third ) regimen was 1.5 - 2 times more likely to induce a positive response OBJECTIVE To evaluate the efficacy and safety of ofloxacin+coamoxiclav versus doxycycline-coamoxiclav in the treatment of chlamydial pelvic infections . DESIGN An open , comparative , r and omised , monocentric study . SUBJECTS A hundred and eighteen patients ( 85 endometritis and 33 salpingitis ) were included . Clinical , laparoscopic and bacteriological assessment s were performed before treatment . 30.4 % of salpingitis were considered as severe ( COGIT score > 6 ) . 25.4 % of acute pelvic infections were only caused by Chlamydia trachomatis . TREATMENT A hundred and eighteen patients were treated orally with 3 week combination ofloxacin ( 200 mg b.i.d . ) + coamoxiclav ( 1 g b.i.d . ) ( n = 60 ) or with a 6 week coamoxiclav ( 1 g b.i.d . ) + doxycycline ( 100 mg b.i.d . ) ( n = 58 ) . RESULTS Oral combination ofloxacin-coamoxiclav is as effective as oral combination doxycycline+coamoxyclav with respectively 96.7 % versus 96.6 % and 100 % versus 98.4 % satisfactory clinical et bacteriological results This prospect i ve , r and omized controlled study compared the efficacy and safety of ciprofloxacin alone versus a conventional two-drug regimen , clindamycin with gentamicin . The study group included 71 patients hospitalized for pelvic infections such as acute ( N=33 ) and chronic ( N=8 ) salpingitis , tubo-ovarian abscesses ( N=11 ) , endometritis ( N=9 ) , septic abortion ( N=3 ) , and other categories ( N=7 ) . Twenty-two of 35 patients on ciprofloxacin and 20 of 36 on clindamycin plus gentamicin had culturable pathogens : gonococci in 28 , anaerobes in six , chlamydia in four , and associated pathogens in 19 . Complete clinical and bacteriologic cure was achieved in 21 of 22 ( 95 % ) in the ciprofloxacin group and 19 of 20 ( 95 % ) in the clindamycin plus gentamicin group . The mean duration of intravenous/oral ciprofloxacin therapy was 3.7/7.2 days , and it was 3/6.6 days for clindamycin plus gentamicin . Ciprofloxacin , a new quinolone , appears to be safe as a single-drug therapy and was as effective as the combination of clindamycin plus gentamicin for the treatment of severe pelvic infections requiring hospitalization The aim of this study was to compare the clinical and bacteriologic efficacy of meropenem with imipenem/cilastatin in the treatment of obstetric and gynecologic infections . This was a controlled , multicenter , r and omized study with two parallel groups and a follow-up period of up to 4 weeks . A total of 105 hospital in- patients requiring antibacterial parenteral therapy were enrolled , 52 in the meropenem group and 53 in the imipenem/cilastatin group . Both drugs were administered at 0.5 g every 8 hours , by slow intravenous infusion over 20 - 30 minutes ; for meropenem the administration by intravenous bolus injection ( over approximately 5 minutes ) was allowed . The mean duration of therapy was 5 days for both treatments . At the end of treatment , all 46 evaluable patients in the meropenem treatment group had a satisfactory clinical response , while in the imipenem/cilastatin group 5/49 patients were clinical failures . The difference between the treatment groups in clinical response was statistically significant ( 100 % vs 89.8 % ; p=.026 ) . A similar result was seen in the intention-to-treat analysis ( 98 % vs 84.6 % ; p=0.017 ) . Both treatments were well tolerated , but fewer meropenem patients experienced treatment-related adverse events in comparison with imipenem/cilastatin ( 11.5 % vs 15.1 % ) OBJECTIVE : To evaluate the equivalence of ceftriaxone plus doxycycline or azithromycin for cases of mild pelvic inflammatory disease ( PID ) . METHODS : Patients with PID received an intramuscular injection of 250 mg of ceftriaxone , and were r and omly assigned to receive 200 mg/d of doxycycline for 2 weeks , or 1 g of azithromycin per week , for 2 weeks . The degree of pain was assessed on days 2 , 7 , and 14 and clinical cure was assessed on day 14 . RESULTS : From 133 patients eligible for the study , 13 were excluded for having conditions other than PID , 11 were lost on follow-up , and three had oral intolerance to the antibiotics , yielding 106 for protocol analysis . No significant difference was observed regarding the degree of pain between the doxycycline and azithromycin groups . Clinical cure per protocol was 98.2 % ( 56 of 57 ; 95 % confidence interval [ CI ] , 0.9–0.99 ) with azithromycin , and 85.7 % ( 42 of 49 ; 95 % CI , 0.72–0.93 ) with doxycycline ( P=0.02 ) . In a modified intention to treat analysis , clinical cure was 90.3 % ( 56 of 62 ; 95 % CI , 0.80–0.96 ) with azithromycin , and 72.4 % ( 42 of 58 ; 95 % CI , 0.58–0.82 ) with doxycycline ( P=.01 ) ; a relative risk of 0.35 , and a number needed to treat of six for benefit with azithromycin . CONCLUSION : When combined with ceftriaxone , 1 g of azithromycin weekly for 2 weeks is equivalent to ceftriaxone plus a 14-day course of doxycycline for treating mild PID . CLINICAL TRIAL REGISTRATION : IS RCT N , http://is rct n.org , IS RCT N46117662 LEVEL OF EVIDENCE : This multicentre , double-blind study was undertaken to demonstrate non-inferiority of once-daily oral moxifloxacin compared with combination therapy in the management of acute , uncomplicated pelvic inflammatory disease ( PID ) . Women aged ≥18 years with PID were r and omized to receive moxifloxacin ( 400 mg once daily ) for 14 days or comparator treatment ( doxycycline [ 100 mg twice daily ] plus metronidazole [ 400 mg three times daily ] for 14 days , plus one single 500-mg ciprofloxacin dose ) . Of the 434 valid per protocol ( PP ) patients , the overall clinical success rates at 2–14 days post-therapy were 96.6 % ( moxifloxacin ) and 98.0 % ( comparator ) ; moxifloxacin was non-inferior to the comparator regimen both in the PP ( 95 % confidence interval [ CI ] : −4.5 , 1.6 ) and intent-to-treat ( 95 % CI : −5.8 , 6.9 ) population s. Clinical success rates at 21–35 days post-therapy were 93.8 % ( 166/177 ; data missing for 47 patients ) for moxifloxacin and 91.3 % ( 147/161 ; data missing for 37 patients ) for the comparator . Bacteriological success rates at 2–14 days post-therapy were 92.5 % ( moxifloxacin ) and 88.2 % ( comparator ) . Once-daily dosing and proven efficacy suggest that moxifloxacin may be of value in acute , uncomplicated PID OBJECTIVE Pelvic inflammatory disease ( PID ) is a common and morbid intraperitoneal infection . Although most women with pelvic inflammatory disease are treated as out patients , the effectiveness of this strategy remains unproven . STUDY DESIGN We enrolled 831 women with clinical signs and symptoms of mild-to-moderate pelvic inflammatory disease into a multicenter r and omized clinical trial of inpatient treatment initiated by intravenous cefoxitin and doxycycline versus outpatient treatment that consisted of a single intramuscular injection of cefoxitin and oral doxycycline . Long-term outcomes were pregnancy rate , time to pregnancy , recurrence of pelvic inflammatory disease , chronic pelvic pain , and ectopic pregnancy . RESULTS Short-term clinical and microbiologic improvement were similar between women r and omized to the inpatient and outpatient groups . After a mean follow-up period of 35 months , pregnancy rates were nearly equal ( 42.0 % for out patients and 41.7 % for in patients ) . There were also no statistically significant differences between outpatient and inpatient groups in the outcome of time to pregnancy or in the proportion of women with pelvic inflammatory disease recurrence , chronic pelvic pain , or ectopic pregnancy . CONCLUSION Among women with mild-to-moderate pelvic inflammatory disease , there was no difference in reproductive outcomes between women r and omized to inpatient treatment and those r and omized to outpatient treatment The clinical efficacy and safety of clindamycin‐gentamicin versus doxycycline‐cefoxitin in the treatment of acute pelvic inflammatory disease was evaluated in a comparative , r and omized , prospect i ve , multicenter study . Ten investigators enrolled 170 patients . Those judged to be eligible for efficacy were 60/88 ( 68 % ) who received the clindamycin‐gentamicin regimen and 55/82 ( 67 % ) of those treated with cefoxitin‐doxycycline . A successful clinical outcome was attained for 52/60 ( 87 % ) and 46/55 ( 84 % ) for patients treated with clindamycin‐gentamicin and cefoxitin‐doxycycline , respectively , a difference that was not statistically significant . In the clindamycin‐gentamicin series , 8/8 ( 100 % ) of patients with positive C. trachomatis culture at baseline were culture negative at the late follow‐up 21–35 days after treatment . For those given cefoxitin‐doxycycline , 9/11 ( 82 % ) who had C. trachomatis at pretreatment showed eradication at follow‐up . Neisseria gonorrhoeae was present at baseline in 8/60 ( 13 % ) of the clindamycin‐gentamicin patients and in 9/55 ( 16 % ) of those treated with cefoxitin‐doxycycline . Of those who had appropriate follow‐up cultures performed , 6 in the clindamycin‐gentamicin group and 8 in the cefoxitin‐doxycycline series , all showed eradication of the organism . It is concluded that clindamycin‐gentamicin and cefoxitin‐doxycycline have similar clinical cure rates for acute pelvic inflammatory disease , and based on this limited experience , it is suggested that the clindamycin‐gentamicin combination will satisfactorily eradicate Chlamydia trachomatis and Neisseria gonorrhoeae when either or both of these pathogens are present The object of this r and omized study was to compare the safety and efficacy of oral ofloxacin , 400 mg twice daily for 10 days , versus intramuscular cefoxitin , 2 gm , plus oral probenecid , 1 gm , followed by oral doxycycline , 100 mg twice daily for 10 days , in the outpatient treatment of uncomplicated acute salpingitis . Thirty-eight women ( 53 % ) had Neisseria gonorrhoeae from their pretreatment endocervical or endometrial cultures , and 18 had Chlamydia trachomatis ( 25 % ) . Thirty-five of 37 women ( 95 % ) treated with the ofloxacin regimen were clinical ly cured , and 34 of 35 ( 97 % ) were cured with the cefoxitin-doxycycline regimen ( p = 0.52 ) . One clinical failure occurred in each group with N. gonorrhoeae infection , and one failure occurred in the ofloxacin group because of side effects . The bacteriologic response for N. gonorrhoeae in both groups was 100 % . The eradication of C. trachomatis was 100 % ( 10/10 ) for the cefoxitin/doxycycline group and 86 % ( 6/7 ) for ofloxacin . The side effects were similar in both groups of subjects . In this study both regimens were effective for the outpatient treatment of uncomplicated acute salpingitis We studied the clinical and microbiological response to two treatment regimens in 36 patients with acute pelvic inflammatory disease ( PID ) . All patients were hospitalized and underwent laparoscopy and endometrial biopsy . Cervical , endometrial , tubal and peritoneal cultures for Chlamydia trachomatis , Neisseria gonorrhoeae , genital mycoplasmas , facultative and anaerobic bacteria and Herpes simplex virus were obtained . The patients were r and omly assigned to two treatment groups : 16 women received ciprofloxacin 200 mg b.i.d . iv . for two days , followed by oral administration with 750 mg b.i.d . to complete a 14-day course of treatment . Twenty women received the combination of doxycycline and metronidazole according to a similar scheme of administration . The response was evaluated with repeated clinical examinations , monitoring of the erythrocyte sedimentation rate and serum C-reactive protein concentration , and repeated microbial culture from the cervix . Ciprofloxacin treatment was successful in all nine patients with chlamydial or gonococcal PID and in six of seven with nonchlamydial nongonococcal PID . Doxycycline plus metronidazole regimen was successful in five of seven patients with chlamydial or gonococcal PID and in nine of 13 patients with nonchlamydial nongonococcal PID . Thus , the overall success rate was 94 % ( 15 of 16 ) with ciprofloxacin and 70 % ( 14 of 20 ) with doxycycline plus metronidazole . Our study suggests that ciprofloxacin is a promising new alternative for the treatment of acute PID Studies have shown that oral contraceptive use may protect against pelvic inflammatory disease ( PID ) , but it is not known whether oral contraceptives protect against the disease among women already infected with Chlamydia trachomatis or Neisseria gonorrhoeae . The relationship between oral contraceptive use and PID was analyzed in a case-control study of 141 women with verified PID and 739 r and omly selected , sexually active women with no clinical evidence of the disease . Case and control subjects were stratified on the basis of infection with C trachomatis , N gonorrhoeae , or neither organism . Among women infected with C trachomatis alone , those with PID were less likely than control subjects to use oral contraceptives . The association was significant when oral contraceptive use was compared with nonuse ( odds ratio , 0.22 ; 95 % confidence interval , 0.08 to 0.64 ) and with noncontraception ( odds ratio , 0.17 ; 95 % confidence interval , 0.06 to 0.53 ) and remained so after adjusting for potential confounding variables by logistic regression analysis . Among women infected with N gonorrhoeae alone , no association was found between use of oral contraceptives and PID . These data suggest that oral contraceptive use protects against symptomatic PID among women infected with C trachomatis but not among those infected with N gonorrhoeae We compared the clinical and microbiologic efficacy of two broad-spectrum combination antimicrobial regimens in the treatment of 148 patients with acute pelvic inflammatory disease . Patients were r and omized to inpatient treatment with either cefoxitin and doxycycline ( n = 75 ) or clindamycin and tobramycin ( n = 73 ) . These antibiotics were administered intravenously for at least 4 days , and up to 48 hours beyond defervescence . Patients were discharged on a regimen of oral doxycycline or clindamycin in accordance with the intravenous regimen to complete a total duration of therapy of 2 weeks . Neisseria gonorrhoeae ( 53 % ) and Chlamydia trachomatis ( 31 % ) were the microorganisms that were isolated most frequently from the genital tract of enrolled patients . At follow-up , N. gonorrhoeae was isolated in two patients , and C. trachomatis was isolated in none . The overall initial favorable response rate to combination antimicrobial therapy was 98.5 % ( 130/132 ) in patients with uncomplicated pelvic inflammatory disease and 81 % ( 13/16 ) in patients with pelvic inflammatory disease that was complicated by tuboovarian abscess . A greater than 70 % decrease in abdominal tenderness score occurred in 89 % of 111 patients within 6 weeks of hospital discharge . There were no significant differences between antibiotic treatment groups in any response categories or in toxicity . During the initial hospitalization , five patients ( three with tuboovarian abscess ; one with a pyosalpinx , and one with intractable acute and chronic pelvic inflammatory disease ) required surgical intervention . These results support the recommendation to use broad-spectrum combination antimicrobial therapy for the treatment of acute pelvic inflammatory disease |
12,180 | 26,342,966 | RESULTS 80 independent studies were review ed and executive functions , emotional memory and the translation of motivation into actions are highlighted as key deficits with a strong evidence base in people with schizophrenia . | BACKGROUND Anhedonia and amotivation are substantial predictors of poor functional outcomes in people with schizophrenia and often present a formidable barrier to returning to work or building relationships .
The Temporal Experience of Pleasure Model proposes constructs which should be considered therapeutic targets for these symptoms in schizophrenia e.g. anticipatory pleasure , memory , executive functions , motivation and behaviours related to the activity .
Recent review s have highlighted the need for a clear evidence base to drive the development of targeted interventions .
OBJECTIVE To review systematic ally the empirical evidence for each TEP model component and propose evidence -based therapeutic targets for anhedonia and amotivation in schizophrenia . | Recent work has suggested that anhedonia in schizophrenia can be understood as involving two separate constructs : deficits in anticipatory and consummatory pleasure . Little is known about the relative stability of these different constructs and their links with clinical features and social function over time . To examine these questions , 51 participants with a diagnosis of schizophrenia or schizoaffective disorder in a non-acute phase of illness were administered the Temporal Experience of Pleasure Scale , the Positive and Negative Syndrome Scale , and Quality of Life Scale at two time points six months apart . Results revealed that baseline scores of both anticipatory and consummatory pleasure were significantly correlated with follow-up scores six months later , suggesting each construct is stable in the short term . The association of anticipatory pleasure at baseline and six months was significantly higher than the relationship between consummatory pleasure at baseline and at six months . Anticipatory pleasure predicted concurrent and prospect i ve levels of positive symptoms , emotional discomfort , and interpersonal function , but not emotion recognition . Consummatory pleasure predicted only concurrent positive symptoms . The link of baseline anticipatory pleasure with emotional discomfort at six months persisted even after controlling for baseline emotional discomfort . Implication s for the measurement and conceptualization of anhedonia in schizophrenia are discussed BACKGROUND Negative symptoms may be associated with dysfunction of the brain reward system in schizophrenia . We used functional magnetic resonance imaging ( fMRI ) to assess the BOLD response in the ventral striatum of unmedicated schizophrenics during presentation of reward-indicating and loss-indicating stimuli . METHODS A total of 10 schizophrenic men ( 7 never medicated , 3 unmedicated for at least 2 years ) and 10 age-matched healthy male volunteers participated in an incentive monetary delay task , in which visual cues predicted that a rapid response to a subsequent target stimulus would result either in monetary gain or loss or would have no consequence . RESULTS Compared to healthy controls , unmedicated schizophrenics showed reduced ventral striatal activation during the presentation of reward-indicating cues . Decreased activation of the left ventral striatum was inversely correlated with the severity of negative ( and trendwise positive ) symptoms . DISCUSSION Reduced activation in one of the central areas of the brain reward system , the ventral striatum , was correlated with the severity of negative symptoms in medication-free schizophrenics . In unmedicated schizophrenic patients , a high striatal dopamine turnover may increase the " noise " in the reward system , thus interfering with the neuronal processing of reward-predicting cues by phasic dopamine release . This , in turn , may contribute to negative symptoms as such as anhedonia , apathy , and loss of drive and motivation Background The Temporal Experience of Pleasure Scale ( TEPS ) is a measure specifically design ed to capture the anticipatory and consummatory facets of pleasure . However , few studies have examined the structure of the measure in non-Western sample s. The current study aim ed to evaluate the factor structure and psychometric properties of the TEPS in a Chinese sample . Methods We administered the Chinese version of the TEPS to 2275 healthy Chinese college students . They were r and omly split into two sub- sample s. The first sub- sample was used for exploratory factor analysis ( EFA ) to examine the structure of the TEPS in a Chinese sample . The second sub- sample was used as a validation sample for the identified structure from the EFA and confirmatory factor analysis ( CFA ) was adopted . Results Results of the EFA suggested a four-factor model ( consummatory context ual , consummatory abstract , anticipatory context ual , and anticipatory abstract factors ) instead of the original two-factor model ( consummatory and anticipatory factors ) ascertained from Western sample s in the United States . The CFA results confirmed these results in the second sub- sample . Internal consistency and test-retest stability of the TEPS factors were good . Conclusions The TEPS has four factors among Chinese participants . Possible reasons for cultural difference and potential applications of the TEPS for cross-cultural comparison are discussed Research on emotional processing in schizophrenia suggests relatively intact subjective responses to affective stimuli " in the moment . " However , neuroimaging evidence suggests diminished activation in brain regions associated with emotional processing in schizophrenia . We asked whether given a more vulnerable cognitive system in schizophrenia , individuals with this disorder would show increased or decreased modulation of working memory ( WM ) as a function of the emotional content of stimuli compared with healthy control subjects . In addition , we examined whether higher anhedonia levels were associated with a diminished impact of emotion on behavioral and brain activation responses . In the present study , 38 individuals with schizophrenia and 32 healthy individuals completed blocks of a 2-back WM task in a functional magnetic resonance imaging scanning session . Blocks contained faces displaying either only neutral stimuli or neutral and emotional stimuli ( happy or fearful faces ) , r and omly intermixed and occurring both as targets and non-targets . Both groups showed higher accuracy but slower reaction time for negative compared to neutral stimuli . Individuals with schizophrenia showed intact amygdala activity in response to emotionally evocative stimuli , but demonstrated altered dorsolateral prefrontal cortex ( DLPFC ) and hippocampal activity while performing an emotionally loaded WM-task . Higher levels of social anhedonia were associated with diminished amygdala responses to emotional stimuli and increased DLPFC activity in individuals with schizophrenia . Emotional arousal may challenge dorsal-frontal control systems , which may have both beneficial and detrimental influences . Our findings suggest that disturbances in emotional processing in schizophrenia relate to alterations in emotion-cognition interactions rather than to the perception and subjective experience of emotion per se CONTEXT Low-functioning patients with chronic schizophrenia have high direct treatment costs and indirect costs incurred due to lost employment and productivity and have a low quality of life ; antipsychotic medications and psychosocial interventions have shown limited efficacy to promote improved functional outcomes . OBJECTIVE To determine the efficacy of an 18-month recovery-oriented cognitive therapy program to improve psychosocial functioning and negative symptoms ( avolition-apathy , anhedonia-asociality ) in low-functioning patients with schizophrenia . Design , Setting , and PARTICIPANTS A single-center , 18-month , r and omized , single-blind , parallel group trial enrolled 60 low-functioning , neurocognitively impaired patients with schizophrenia ( mean age , 38.4 years ; 33.3 % female ; 65.0 % African American ) . INTERVENTIONS Cognitive therapy plus st and ard treatment vs st and ard treatment alone . MAIN OUTCOME MEASURES The primary outcome measure was the Global Assessment Scale score at 18 months after r and omization . The secondary outcomes were scores on the Scale for the Assessment of Negative Symptoms and the Scale for the Assessment of Positive Symptoms at 18 months after r and omization . RESULTS Patients treated with cognitive therapy showed a clinical ly significant mean improvement in global functioning from baseline to 18 months that was greater than the improvement seen with st and ard treatment ( within-group Cohen d , 1.36 vs 0.06 , respectively ; adjusted mean [ SE ] , 58.3 [ 3.30 ] vs 47.9 [ 3.60 ] , respectively ; P = .03 ; between-group d = 0.56 ) . Patients receiving cognitive therapy as compared with those receiving st and ard treatment also showed a greater mean reduction in avolition-apathy ( adjusted mean [ SE ] , 1.66 [ 0.31 ] vs 2.81 [ 0.34 ] , respectively ; P = .01 ; between-group d = -0.66 ) and positive symptoms ( hallucinations , delusions , disorganization ) ( adjusted mean [ SE ] , 9.4 [ 3.3 ] vs 18.2 [ 3.8 ] , respectively ; P = .04 ; between-group d = -0.46 ) at 18 months . Age was controlled in the analyses , and there were no meaningful group differences in baseline antipsychotic medications ( class or dosage ) or in medication changes during the course of the trial . CONCLUSION Cognitive therapy can be successful in promoting clinical ly meaningful improvements in functional outcome , motivation , and positive symptoms in low-functioning patients with significant cognitive impairment . Trial Registration clinical trials.gov Identifier : NCT00350883 BACKGROUND Cognitive difficulties are prevalent in people with a diagnosis of schizophrenia and are associated with poor long-term functioning . AIMS To evaluate the effectiveness of cognitive remediation therapy on cognitive difficulties experienced by people with schizophrenia . METHOD Participants with a diagnosis of schizophrenia , a social behaviour problem and a cognitive difficulty ( n=85 ) were r and omised to 40 sessions of cognitive remediation or treatment as usual in a single-blind r and omised controlled trial . Working memory , cognitive flexibility and planning , were measured at weeks 0,14 and 40 . RESULTS There were durable improvements in working memory ( advantage 1.33 points , 95 % CI 0.43 - 2.16 , st and ardised effect size 0.34 ) as well as an indication of improvement in cognitive flexibility . Memory improvement predicted improvement in social functioning . Costs were lower in the cognitive remediation group following therapy but rose at follow-up . However , cost-effectiveness analyses showed that improvements in memory were achieved at little additional cost . CONCLUSIONS Cognitive remediation therapy is associated with durable improvements in memory , which in turn are associated with social functioning improvements in people with severe mental illness Startle-elicited blinks were measured during the presentation of affective slides in order to investigate emotional responsiveness in 24 male healthy subjects and 34 male schizophrenic patients . Although the two groups did not differ with regard to their subjective and autonomic responses to the slide stimuli , there was a significant difference between the groups in their responses to the startle probes . Patients rated low in affective expression showed a linear response pattern comparable to that of normal controls with largest amplitudes during unpleasant slides and smallest during pleasant slides . Patients without apparent deficit in affective expression showed a quadratic relationship with smaller blink amplitudes during both pleasant and unpleasant slides . Diminished affective expression rated on the basis of a clinical interview is not associated with a general attenuation of the blink reflex or of its modulation by exposure to emotional slides . Thus , we found no indication of an impairment in the perception of affective stimuli nor of reduced appreciation of pleasant stimuli ( anhedonia ) in these patients A dysfunction of central dopaminergic neurotransmission has been found in various neuropsychiatric diseases , and may be associated with a common psychopathological correlate . One hypothesis suggests that dopaminergic stimulation of the brain reward system reinforces behavior because it is experienced as pleasurable , and that dopaminergic dysfunction leads to anhedonia , the inability to experience pleasure . An alternative hypothesis assumes that dopaminergic stimulation does not promote pleasure or " liking " of a reward but rather mediates " wanting " of a reward , and suggests that dopaminergic dysfunction is associated with a failure to be motivated by stimuli that indicate reward . We measured negative symptoms , psychomotor slowing and dopamine receptor sensitivity in twelve drug-free patients with major depression , seventeen alcohol-dependent and sixteen opiate-dependent patients , ten schizophrenics with neuroleptic medication , and ten healthy controls . The sensitivity of central dopamine receptors was assessed with the growth hormone response to apomorphine application . Psychomotor slowing was measured in a reaction-time test and anhedonia and other negative symptoms were assessed with self-rating scales and the Scale for the Assessment of Negative Symptoms . Patients with major depression , alcohol dependence and neuroleptic medication displayed a reduced sensitivity of central dopamine receptors compared to control subjects . Anhedonia was not a common correlate of dopamine receptor dysfunction . Instead , affective flattening was associated with both dopamine receptor sensitivity and psychomotor slowing . Our findings thus do not support the anhedonia hypothesis of central dopaminergic dysfunction . Rather , affective flattening may result from the lack of an emotional response towards reward-indicating stimuli . These findings indicate that patients with dopaminergic dysfunction are not unable to experience pleasure , but may fail to be motivated by environmental stimuli to seek reward |
12,181 | 20,386,241 | Both short- and long-term interventions can improve self-efficacy demonstrating that the duration of the intervention can vary and still be successful .
Existing evidence suggests that it is not the amount of education ( number of sessions/length of sessions ) that improves self-efficacy , but some other factor or factors that remain unknown at present . | PURPOSE The purpose of this study was to conduct a systematic review of the literature to better underst and how to structure educational interventions for heart failure patients to improve their self-efficacy for self-care behaviors . | Background Self-management programs for patients with heart failure can reduce hospitalizations and mortality . However , no programs have analyzed their usefulness for patients with low literacy . We compared the efficacy of a heart failure self-management program design ed for patients with low literacy versus usual care . Methods We performed a 12-month r and omized controlled trial . From November 2001 to April 2003 , we enrolled participants aged 30–80 , who had heart failure and took furosemide . Intervention patients received education on self-care emphasizing daily weight measurement , diuretic dose self-adjustment , and symptom recognition and response . Picture-based educational material s , a digital scale , and scheduled telephone follow-up were provided to reinforce adherence . Control patients received a generic heart failure brochure and usual care . Primary outcomes were combined hospitalization or death , and heart failure-related quality of life . Results 123 patients ( 64 control , 59 intervention ) participated ; 41 % had inadequate literacy . Patients in the intervention group had a lower rate of hospitalization or death ( crude incidence rate ratio ( IRR ) = 0.69 ; CI 0.4 , 1.2 ; adjusted IRR = 0.53 ; CI 0.32 , 0.89 ) . This difference was larger for patients with low literacy ( IRR = 0.39 ; CI 0.16 , 0.91 ) than for higher literacy ( IRR = 0.56 ; CI 0.3 , 1.04 ) , but the interaction was not statistically significant . At 12 months , more patients in the intervention group reported monitoring weights daily ( 79 % vs. 29 % , p < 0.0001 ) . After adjusting for baseline demographic and treatment differences , we found no difference in heart failure-related quality of life at 12 months ( difference = -2 ; CI -5 , + 9 ) . Conclusion A primary care-based heart failure self-management program design ed for patients with low literacy reduces the risk of hospitalizations or death Background Peak oxygen uptake ( VO2 ) testing is commonly used to assess chronic heart failure ( CHF ) patients ’ exercise tolerance . The test requires maximal effort ; however , many participants have low confidence ( self-efficacy ) to perform optimally . Purpose This r and omized controlled trial examined the effectiveness of a modeling intervention to increase Peak VO2 ( PVO2 ) and self-efficacy in people diagnosed with CHF . Methods Twenty participants with a diagnosis of CHF were r and omized to either an intervention ( modeling DVD ) or a control group . Both groups completed a measure of self-efficacy prior to performing two PVO2 tests , each separated by 7 days . After completing the first test ( T1 ) the intervention group watched a 10-min coping model DVD . All participants returned 1 week later ( T2 ) to complete identical study procedures . Results Analysis of covariance results showed that compared with the participants in the control group , those assigned to the modeling intervention had higher PVO2 at T2 , F ( 1 , 19 ) = 4.38 , p = 0.05 , ή2 = 0.21 and self-efficacy , F ( 1 , 19 ) = 5.80 , p < 0.05 , ή2 = 0.25 . Only partial support was found for change in self-efficacy mediating treatment outcome ( PVO2 ) . Conclusions Watching a modeling video is associated with increased PVO2 and self-efficacy . These results have implication s for testing patients in a clinical setting to maximize exercise tolerance test results OBJECTIVES This study evaluated the effectiveness ( changes in health behaviors , health status , and health service utilization ) of a self-management program for chronic disease design ed for use with a heterogeneous group of chronic disease patients . It also explored the differential effectiveness of the intervention for subjects with specific diseases and comorbidities . METHODS The study was a six-month r and omized , controlled trial at community-based sites comparing treatment subjects with wait-list control subjects . Participants were 952 patients 40 years of age or older with a physician-confirmed diagnosis of heart disease , lung disease , stroke , or arthritis . Health behaviors , health status , and health service utilization , as determined by mailed , self-administered question naires , were measured . RESULTS Treatment subjects , when compared with control subjects , demonstrated improvements at 6 months in weekly minutes of exercise , frequency of cognitive symptom management , communication with physicians , self-reported health , health distress , fatigue , disability , and social/role activities limitations . They also had fewer hospitalizations and days in the hospital . No differences were found in pain/physical discomfort , shortness of breath , or psychological well-being . CONCLUSIONS An intervention design ed specifically to meet the needs of a heterogeneous group of chronic disease patients , including those with comorbid conditions , was feasible and beneficial beyond usual care in terms of improved health behaviors and health status . It also result ed in fewer hospitalizations and days of hospitalization BACKGROUND Outcomes related to chronic heart failure ( HF ) remain relatively poor , despite advances in pharmacological therapy and medical and nursing care . Experts agree that outpatient care may be among the factors that affect HF outcomes . We hypothesized that the method by which outpatient care is delivered may affect outcomes in this patient population . METHODS A prospect i ve , r and omized design was used to compare HF outcomes from 216 patients r and omized to 1 of 2 home health care delivery methods for 3 months after discharge . Care was delivered by the home nurse visit ( HNV ) or the nurse telemanagement ( NTM ) method . In the latter , patients used transtelephonic home monitoring devices to measure their weight , blood pressure , heart rate , and oxygen saturation . These data were transmitted daily to a secure Internet site . An advanced- practice nurse worked collaboratively with a cardiologist and subsequently treated patients via the telephone . Both delivery methods used the same HF-specific clinical guidelines to direct care . Outcomes include HF readmissions and length of stay , anxiety , depression , self-efficacy , and quality of life . Data were primarily tested using a 2-group analysis of variance ( ANOVA ) . We used a repeated- measures ANOVA to conduct preintervention-postintervention analyses . RESULTS After 3 months , patients in the NTM group ( n = 108 ; mean + /- SD age , 62.9 + /- 13.2 years ; 83 % African American ; 64 % female ) had fewer HF readmissions ( 13 vs 24 ; P</=.001 ) with shorter lengths of stay ( 49.5 vs 105.0 days ; P</=.001 ) compared with the HNV group ( n = 108 ; mean + /- SD age , 63.2 + /- 12.6 years ; 89 % African American ; 62 % female ) . Hospitalization charges at 3 months were less in the NTM group compared with the HNV group ( $ 65 023 vs $ 177 365 ; P</=.02 ) . At 6 and 12 months , cumulative readmission charges in the NTM group were also less ( $ 223 638 vs $ 500 343 [ P<.03 ] and $ 541 378 vs $ 677 710 [ P</=.16 ] , respectively ) compared with the HNV group . Quality of life was significantly improved for both groups when we compared postintervention and preintervention scores . CONCLUSION The adaptation of state-of-the-art computerized technology to closely monitor patients with HF with advanced- practice nurse care under the guidance of a cardiologist significantly improves HF management while reducing the cost of care Nonadherence to medical treatment among heart failure patients is high and results in frequent exacerbations and premature death . This treatment-only pilot study examined whether a year-long group-based self-management intervention is feasible and improves self-management skills in patients with mild-to-moderate heart failure ( ejection fraction < or = 40 % and New York Heart Association functional class I , II , or III ) . A total of 31 of 100 recruited patients ( 31 % ) agreed to participate . Twenty-six ( 84 % ) completed the year-long self-management program . Compared with baseline , the intervention was associated with an increase in overall self-efficacy in practicing self-management skills ( p<0.001 ) and in four of five specific self-management skills . Patients and their group leaders also reported an increase in actual use of self-management skills ( p<0.001 ) and in several psychosocial outcomes . The success of this pilot study suggests the need for a r and omized clinical trial to test the efficacy of group-based self-management training on medical outcomes BACKGROUND Heart failure is a common and important cause of morbidity and mortality . Disease management offers promise in reducing the need for hospitalization and improving quality of life for heart failure patients , but experimental data on the efficacy of such programs are limited . METHODS AND RESULTS A total of 151 patients hospitalized with heart failure were r and omized to usual care or scheduled telephone calls by specially trained nurses promoting self-management and guideline -based therapy as prescribed by primary physicians . Nurses also screened patients for heart failure exacerbations , which they managed with supplemental diuretics or by contacting the primary physician for instructions . Outcomes included time to hospital encounter , mortality , number and cost of hospitalizations , functional status , and satisfaction with care . Intervention patients had a longer time to encounter ( hazard ratio [ HR ] = 0.67 ; 95 % confidence interval [ CI ] 0.47 - 0.96 ; P = .029 ) , hospital readmission ( HR = 0.67 ; CI 0.46 - 0.99 ; P = .045 ) , and heart failure-specific readmission ( HR = 0.62 ; CI 0.38 - 1.03 ; P = .063 ) . The number of admissions , hospital days , and hospital costs were significantly lower during the first 6 months after intervention but not at 1 year . The intervention had little effect on functional status , mortality , and satisfaction with care . CONCLUSION A nurse-administered , telephone-based disease management program delayed subsequent health care encounters , but had minimal impact on other outcomes OBJECTIVE Patients with heart failure need education and support to improve knowledge and self-care . Shared medical groups that provide education and support have been successful in other patient population s. This study compares an advanced practice nurse-led shared medical appointment intervention in the office setting with st and ard care relative to self-care and knowledge among community-living adults with heart failure . METHODS Participants were r and omized to shared appointment and st and ard care groups , and completed the Heart Failure Knowledge Test and Self-Care Heart Failure Index at baseline and 8 weeks . RESULTS From baseline to 8 weeks , Heart Failure Knowledge Test scores improved more for the intervention group than the control group ( F time X group = 4.90 , df = 1.21 ; P = .038 ) . There was no difference in groups ' rates of change on the total Self-Care Heart Failure Index . CONCLUSION The findings reveal improved knowledge when education and support are provided in a shared medical appointment setting . The shared medical visit model may be feasible as a way to provide patients with heart failure and their families with ongoing education and a supportive environment The purpose of this pilot study was to ( a ) determine the feasibility of providing a heart failure disease management program through an in-home telehealth communication device ( Health Buddy ® ) and ( b ) compare the effectiveness of the Health Buddy ® with traditional home management strategies ( telephonic , home visit ) in achieving selected patient outcomes ( self-efficacy , functional status , depression , and health-related quality of life ) . Ninety participants completed the study through 2 months . Thirty percent of participants were either eliminated prior to or withdrawn after enrollment from the study based on Health Buddy ® issues . A mixed model ANOVA revealed those who received telephonic disease management experienced decreased confidence in their ability to manage their heart failure whereas all other groups experienced increased confidence . Further ANOVA analyses indicated improvement over time with no group differences for functional status , depression , or health-related quality of life . These findings suggest that delivering a disease management program through a telehealth communication device is feasible and may be as effective as traditional methods BACKGROUND Self-management of dietary sodium restriction by persons with heart failure ( HF ) is difficult and usually occurs within the home setting and within a family context . OBJECTIVE To compare a patient and family education ( EDUC ) intervention with a combined education and family partnership intervention ( EDUC + FPI ) for effects on improving dietary sodium self-management in persons with HF . METHODS Patients with HF and a family member ( FM ) were r and omized to EDUC ( n = 29 dyads ) or EDUC + FPI ( n = 32 dyads ) . Participants with HF were primarily White males with a mean age of 61 years ( + /-12 ) . The FMs were primarily women and spouses and had a mean age of 54 years ( + /-17 ) . Self-reported dietary sodium ( Diet NA ) intake and 24-hr urinary sodium ( Urine NA ) were measured at baseline ( BL ) and 3 months ( 3 M ) after intervention . Data were analyzed with descriptive statistics , generalized least squares regression , paired t test , and chi-square test . RESULTS Groups did not differ by age , gender , or clinical variables ; however , family functioning ( Family APGAR ) scores were slightly higher in the EDUC + FPI group at BL . Both groups decreased Diet NA and Urine NA from BL to 3 M ; the EDUC + FPI group showed greater decrease in Urine NA and had a greater percentage of those who decreased Urine NA by at least 15 % ( p = .04 ) . Regression analysis to predict Urine NA revealed a significant Group x Time interaction ( p = .03 ) when accounting for time-varying measures of body mass index ( p = .001 ) . DISCUSSION A family-focused intervention may be useful in reducing dietary sodium intake in persons with HF . The Urine NA results support the importance of incorporating family-focused education and support interventions into HF care Peer support has been used effectively in a variety of patient population s , but its effectiveness in improving outcomes in persons with chronic heart failure has not been explored . We trained 9 persons with heart failure to mentor other heart failure patients and tested the effectiveness of this approach in a r and omized controlled clinical trial . A low proportion ( 37 % ) of the eligible population of hospitalized patients agreed to participate . At the end of the 3-month trial , there was significantly higher heart failure self-care in the intervention group ( P < .05 ) . The only difference in social support was a significant decline in perceived support reciprocity in the intervention group ( F = 5.94 , P = .004 ) . No significant group differences in heart failure readmissions , length of stay , or cost were evident at 90-days , although the heart failure readmission rate was 96 % higher in the intervention group when compared to that in the control group . The reasons for low overall enrollment and high readmission rates in the intervention group require further study . Including additional self-care education by a professional , rather than leaving all the education to the mentor , could strengthen the peer support intervention trialed in this study . Small group meetings may be less intrusive and more desirable for this patient population UNLABELLED Development and pilot testing of a disease management program for low literacy patients with heart failure . BACKGROUND R and omized trials have shown that disease management programs can reduce hospitalizations and improve symptoms for patients with congestive heart failure . We sought to create and pilot test such a program for patients with low literacy skills . METHODS We used focus groups and individual cognitive response interviews ( CRIs ) to develop an educational booklet for low literacy patients with heart failure . We incorporated the booklet into a disease management intervention that also included an initial individualized 1-h educational session and scheduled supportive phone calls that were tapered over 6 weeks . We then conducted a 3-month before-after study on patients with low literacy skills ( < 9th grade literacy level ) in a university internal medicine clinic to test the acceptability and efficacy of our program . Outcomes of interest included heart failure-related knowledge , self-care behavior and heart failure-related symptoms measured on the Minnesota Living with Heart Failure ( MLwHF ) scale . RESULTS Twenty-five patients were enrolled and 23 ( 92 % ) completed 3-month follow-up . Mean age was 60 years ( range 35 - 74 ) , 60 % were men , 60 % were African-American , and 74 % had household income under $ 15,000 per year . The median reading level was fifth grade with 32 % reading at or below the third grade level . Mean knowledge score at baseline was 67 % and did not improve after the intervention . The proportion of patients reporting weighing themselves daily increased from 32 % at baseline to 100 % at 12 weeks . Mean improvement on the MLwHF scale was 9.9 points over the 3-month trial ( 95 % CI : 0.5 , 19.2 ) , which corresponds to an improvement in one class on the New York Heart Association heart failure scale . CONCLUSION A heart failure disease management program design ed specifically for patients with low literacy skills is acceptable and is associated with improvement in self-care behavior and heart failure related symptoms |
12,182 | 24,743,684 | Regarding the four elements of MES : i ) weight gain : the prospect i ve studies supported etiological roles for relationship stress , perceived stress , and distress , while the studies on work-related stress ( WS ) showed conflicting results ; ii ) dyslipidemi : too few studies on psychosocial stress as a risk factor for dyslipidemia were available to draw a conclusion ; however , a trend toward a positive association was present ; iii ) type 2 diabetes mellitus ( DM2 ) : prospect i ve studies supported perceived stress and distress as risk factors for the development of DM2 among men , but not among women , while WS was generally not supported as a risk factor among neither men nor women ; iv ) hypertension : marital stress and perceived stress might have an influence on blood pressure ( BP ) , while no association was found regarding distress .
Evaluating WS the results were equivocal and indicated that different types of WS affected the BP differently between men and women .
In conclusion , a longitudinal association between chronic psychosocial stress and the development of MES seems present . | Chronic psychosocial stress has been proposed as a risk factor for the development of the metabolic syndrome ( MES ) .
This review gives a systematic overview of prospect i ve cohort studies investigating chronic psychosocial stress as a risk factor for incident MES and the individual elements of MES . | AIM To explore incident cases of diagnosed diabetes over 35 years of follow-up in relation to self-perceived stress at baseline . METHODS This was a population -based r and om sample of 7251 men derived from the Primary Prevention Trial Study , aged 47 - 56 years at baseline and without prior history of diabetes , coronary heart disease and stroke . Incident diabetes was identified from hospital discharge and death registries as principal or secondary diagnosis . Cox proportional hazards regression was used to evaluate the potential association between stress and diabetes . RESULTS During a 35-year follow-up , a total of 899 men were identified with diabetes . The crude incidence was 5.2 per 1000 persons-years . At baseline , 15.5 % men reported permanent stress related to conditions at work or home . After adjusting for age and competing risk of death , the estimated 35-year conditional probability of diabetes in men with permanent stress was 42.6 % , compared with 31.0 % for those with periodic stress and 31.2 % with no stress . In age-adjusted Cox regression analysis , men with permanent stress had a higher risk of diabetes [ hazard ratio 1.52 ( 95 % CI 1.26 - 1.82 ) ] compared with men with no ( referent ) or periodic stress [ hazard ratio 1.09 ( 95 % CI 0.94 - 1.27 ) ] . The association between stress and diabetes was slightly attenuated but remained significant after adjustment for age , socio-economic status , physical inactivity , BMI , systolic blood pressure and use of anti-hypertensive medication [ hazard ratio 1.45 ( 95 % CI 1.20 - 1.75 ) ] . When examining principal diagnosis of diabetes cases separately from secondary diagnoses cases , the excess risk of diabetes associated with permanent stress remained significant both in age ( only ) and multivariable adjusted models . CONCLUSION Self-perceived permanent stress is an important long-term predictor of diagnosed diabetes , independently of socio-economic status , BMI and other conventional Type 2 diabetes risk factors A new cohort study links work-related stress to an increased risk of developing type 2 diabetes mellitus ( T2DM ) in women , but the findings are less clear in men . R and omized controlled studies are now needed to determine whether management of stress could be used to reduce the risk of developing T2DM BACKGROUND Social inequalities in the incidence of type 2 diabetes and the relation of health behaviors and psychosocial factors to the incidence of type 2 diabetes are not well established . METHODS Prospect i ve occupational cohort study of 10 308 civil servants aged 35 to 55 years at baseline in phase 1 ( 1985 - 1988 ) . Diagnosis of diabetes was ascertained by question naire at baseline and follow-up at phases 2 ( 1989 ) , 3 ( 1992 - 1993 ) , 4 ( 1995 ) , and 5 ( 1997 - 1999 ) and glucose tolerance tests in phases 3 and 5 . RESULTS Participants working in the lower employment grade s had a higher incidence of diabetes than those in higher employment grade s ( men : odds ratio [ OR ] , 2.9 ; 95 % confidence interval [ CI ] , 1.9 - 4.4 ; women : OR , 1.7 [ 95 % CI , 0.8 - 3.7 ] ) . Body mass index and other risk factors considered traditional for type 2 diabetes were found to be so in this cohort . In men , of the psychosocial risk factors examined , only effort-reward imbalance was related to incidence of diabetes ( OR , 1.7 [ 95 % CI , 1.0 - 2.8 ] ) . The General Health Question naire depression subscale was related to incidence of diabetes and impaired glucose tolerance ( OR , 1.25 [ 95 % CI , 1.0 - 1.6 ] ) . These associations remained after adjustment for other confounding factors . In men only , social difference in incidence of diabetes was reduced but still significant after adjustment for conventional risk factors . CONCLUSIONS An inverse relationship exists between social position and incidence of diabetes that is partly explained by health behaviors and other risk factors . Effort-reward imbalance , which is reportedly associated with coronary heart disease , is also associated with type 2 diabetes Positive energy balance is the major cause of obesity , and chronic stress may be a contributory factor . The authors examined cumulative work stress , using the Job Strain Question naire on four occasions , as a predictor of obesity in a prospect i ve 19-year study of 6,895 men and 3,413 women ( aged 35 - 55 years ) in the Whitehall II cohort in London , United Kingdom ( baseline : 1985 - 1988 ) . A dose-response relation was found between work stress and risk of general obesity ( body mass index > or = 30 kg/m(2 ) ) and central obesity ( waist circumference > 102 cm in men , > 88 cm in women ) that was largely independent of covariates . The imputed odds ratios of body mass index obesity for one , two , and three or more reports of work stress adjusted for age , sex , and social position were 1.17 , 1.24 , and 1.73 ( trend p < 0.01 ) , respectively . For waist obesity , the corresponding findings were 1.17 , 1.41 , and 1.61 ( trend p < 0.01 ) . Work stress effect was modestly attenuated after exclusion of obese individuals at baseline and further adjustments for smoking ; intakes of dietary fiber , fruits and vegetables , and alcohol ; and levels of physical activity during follow-up . This study provides prospect i ve , population -based evidence that chronic work stress predicts general and central obesity OBJECTIVES To determine whether men and women with repeated ERI exposure have increased BP means or higher hypertension incidence over a 3-year follow-up . To examine the potential modifying effect of age and overcommitment . METHODS The study cohort was composed of 1,595 white-collar workers ( 629 men and 966 women ) assessed at baseline and 3-year follow-up . Ambulatory BP measures were taken every 15 min during a working day . ERI at work was self-reported using vali date d scales . BP means at follow-up and cumulative incidence of hypertension were respectively modeled with analyses of covariance ( ANCOVA ) and log-binomial regression . RESULTS Among men , no association was observed between repeated ERI exposure and BP . Among women , age had a modifying effect . Women < 45 years old exposed to ERI at both times had significantly higher BP means at follow-up ( 122.2/78.9 mmHg ) than those unexposed ( 120.4/77.4 mmHg ) . In women ≥45 years old , the cumulative incidence of hypertension was 2.78 ( 95 % CI : 1.26 - 6.10 ) times higher among those exposed to ERI at both times . Men and women in the higher tertile of overcommitment had higher BP means ( men : 128.9/82.2 mmHg , women : 121.9/78.0 mmHg ) than those in the lower tertile ( men : 127.2/81.3 mmHg , women : 120.6/77.0 mmHg ) . CONCLUSION This prospect i ve study showed that , among women , repeated ERI exposure led to a significant age-specific increase in BP means and a major age-specific increase in hypertension incidence . These results suggest that primary intervention aim ed at reducing ERI may contribute to lower BP and prevent hypertension in women OBJECTIVES We evaluated whether cumulative exposure to job strain increases blood pressure . METHODS A prospect i ve study of 8395 white-collar workers was initiated during 1991 to 1993 . At follow-up , 7.5 years later , 84 % of the participants were reassessed to estimate cumulative exposure to job strain . RESULTS Compared with men who had never been exposed , men with cumulative exposure and those who became exposed during follow-up showed significant systolic blood pressure increments of 1.8 mm Hg ( 95 % confidence interval [CI]=0.1 , 3.5 ) and 1.5 mm Hg ( 95 % CI=0.2 , 2.8 ) , respectively , and relative risks of blood pressure increases in the highest quintile group of 1.33 ( 95 % CI = 1.01 , 1.76 ) and 1.40 ( 95 % CI = 1.14 , 1.73 ) . Effect magnitudes were smaller among women . Effects tended to be more pronounced among men and women with low levels of social support at work . CONCLUSIONS Among these white-collar workers , exposure to cumulative job strain had a modest but significant effect on systolic blood pressure among men . The risk was of comparable magnitude to that observed for age and sedentary behavior . Men and women with low levels of social support at work appeared to be at higher risk for increases in blood pressure OBJECTIVES We investigated whether exposure to negative aspects of close relationships was associated with subsequent increase in body mass index ( BMI ) and waist circumference . METHODS Data came from a prospect i ve cohort study ( Whitehall II ) of 9425 civil servants aged 35 to 55 years at baseline ( phase 1 : 1985 - 1988 ) . We assessed negative aspects of close relationships with the Close Persons Question naire ( range 0 - 12 ) at phases 1 and 2 ( 1989 - 1990 ) . We measured BMI and waist circumference at phases 3 ( 1991 - 1994 ) and 5 ( 1997 - 1999 ) . Covariates at phase 1 included gender , age , marital status , ethnicity , BMI , employment grade , smoking , physical activity , fruit and vegetable consumption , and common mental disorder . RESULTS After adjustment for sociodemographic characteristics and health behaviors , participants with higher exposure to negative aspects of close relationships had a higher likelihood of a 10 % or greater increase in BMI and waist circumference ( odds ratios per 1-unit increase 1.08 [ 95 % confidence interval ( CI ) = 1.02 , 1.14 ; P = .007 ] and 1.09 [ CI = 1.04 , 1.14 ; P ≤ .001 ] , respectively ) as well as a transition from the overweight ( 25 ≤ BMI < 30 ) to the obese ( BMI ≥ 0 ) category . CONCLUSIONS Adverse social relationships may contribute to weight gain Background Review s have shown that depression is a risk factor for the development of type 2 diabetes . However , there is limited evidence for general psychological distress to be associated with incident diabetes . The aim of the present study was to test whether persons who report higher levels of psychological distress are at increased risk to develop type 2 diabetes during 18 years follow up , adjusted for confounders . Methods A prospect i ve analysis using data from 9,514 participants ( 41 years , SD=14 ; 44 % men ) of the British Household Panel Survey . The General Health Question naire 12 item version was used to assess general psychological distress , diabetes was measured by means of self-report . Cox proportional hazards regression models were used to calculate the multivariate-adjusted hazard ratio ( HR ) of incident diabetes during 18 years follow up , comparing participants with low versus high psychological distress at baseline ( 1991 ) . Results A total of 472 participants developed diabetes 18 year follow up . Those with a high level of psychological distress had a 33 % higher hazard of developing diabetes ( HR=1.33 , 95 % CI 1.10–1.61 ) , relative to those with a low level of psychological distress , adjusted for age , sex , education level and household income . After further adjustment for differences in level of energy , health status , health problems and activity level , higher psychological distress was no longer associated with incident diabetes ( HR=1.10 , 95 % CI 0.91 - 1.34 ) . Conclusions Higher levels of psychological distress are a risk factor for the development of diabetes during an 18 year follow up period . This association may be potentially mediated by low energy level and impaired health status Two studies investigate the effect of stress on food choice . Experiment 1 demonstrates experimentally that stress causes changes in food choice away from healthy low fat foods ( grapes ) to less healthy high fat foods ( M&Ms ) , confirming previous survey research . Experiment 2 , a survey study , finds that more females than males report increasing food consumption when stressed . A much larger percentage of those who report increasing their food consumption when stressed ( 71 % ) are restrained eaters ( i.e. , dieters ) than are people who undereat or who do not change the amount they eat when stressed ( 35 % ) . The foods that they report overeating when stressed are foods they normally avoid for weight-loss or health reasons ( i.e. , highly caloric high fat snack foods ) . They report eating these foods to feel better . Both studies show that stress not only increases consumption in certain individuals but also shifts their food choice from lower fat to higher fat foods OBJECTIVE To investigate the prospect i ve influence of work stress on type 2 diabetes ( T2D ) . RESEARCH DESIGN AND METHODS This population -based cohort included 3,205 women and 2,227 men , aged 35–56 years , with baseline normal glucose tolerance measured with oral glucose tolerance test . At follow-up 8–10 years later , T2D was diagnosed in 60 women and 111 men . Work stress factors evaluated by question naire ( i.e. , dem and s , decision latitude , job strain , shift work , overtime work , and also sense of coherence ) were studied in association with T2D . Odds ratios ( ORs ) and 95 % CIs adjusted for age , education , BMI , physical activity , smoking , family history of diabetes , and psychological distress were calculated . RESULTS In women , low decision latitude was associated with T2D on its own ( OR 2.4 [ 95 % CI 1.1–5.2 ] ) and combined with high dem and s : job strain ( OR 4.2 [ 2.0–8.7 ] ) , adjusted for all available potential confounders . Also , shift work increased the risk of T2D in women ( OR 2.2 [ 1.0–4.7 ] ) when adjusted for age , education , and psychological distress , although this risk was diluted after multifactor adjustment ( OR 1.9 [ 0.8–4.4 ] ) . In men , high work dem and s and high strain decreased the risk of T2D ( OR 0.5 [ 0.3–0.9 ] ) for both measures , as did an active job ( high dem and s and high decision latitude , OR 0.4 [ 0.2–0.9 ] ) . CONCLUSIONS Work stress and shift work may contribute to the development of T2D in women . In men , the risk was decreased by high work dem and s , high strain , and an active job BACKGROUND Of psychosocial stressors , job strain has been associated with a sustained increase in blood pressure . The impact of marital factors on blood pressure and target organ has not been explored . OBJECTIVES To evaluate whether marital adjustment , measured at baseline by self-report ( Dyadic Adjustment Scale ) influences left ventricular mass index ( LVMI ) and ambulatory blood pressure measured over 3 years in patients with mild hypertension . METHODS A prospect i ve cohort study was conducted on 103 cohabiting males or females , including 72 with technically adequate echocardiograms , who at baseline were unmedicated , employed , and living with a significant other , all for a minimum of 6 months and had repeated elevated office diastolic blood pressure . MAIN OUTCOME MEASURES Left ventricular mass by M-mode echocardiography indexed to body surface area and blood pressure were measured by ambulatory blood pressure every 15 minutes ( daytime ) and hourly between 11 PM and 7 AM . RESULTS Marital adjustment , smoking , drinking , and baseline LVMI contributed significantly to the prediction of 3-year LVMI ( semipartial correlation , sr(2 ) = 0.04 , 0.07 , 0.03 , and 0.22 ; P = .03,.008,.08 , and < .001 , respectively ) together accounting for 36 % of the total variability in follow-up LVMI . Three-year ambulatory blood pressure measures were not significantly related to marital adjustment but there were correlations with Dyadic Adjustment Scale subscales . Low or high levels of spousal contact during 3-year ambulatory blood pressure monitoring were associated with an increase or decrease of 3-year , 24-hour diastolic blood pressure , consistent with the quality of marital adjustment ( P = .04 ) or marital satisfaction ( Dyadic Adjustment Scale subscale , P = .008 ) . CONCLUSIONS In a cohort of subjects with mild essential hypertension , marital adjustment had an influence on 3-year LVMI . Depending on the quality of marital adjustment , spousal contact at 3 years was associated with an increase or decrease of 3-year diastolic blood pressure . Confirmation of these results , including objective marital assessment and the participation of normotensive subjects , is required . Arch Intern Med . 2000;160:3453 - 3458 Abstract Objective : To examine the association between work stress , according to the job strain model and the effort-reward imbalance model , and the risk of death from cardiovascular disease . Design : Prospect i ve cohort study . Baseline examination in 1973 determined cases of cardiovascular disease , behavioural and biological risks , and stressful characteristics of work . Biological risks were measured at 5 year and 10 year follow up . Setting : Staff of a company in the metal industry in Finl and . Participants : 812 employees ( 545 men , 267 women ) who were free from cardiovascular diseases at baseline . Main outcome measure : Cardiovascular mortality 1973 - 2001 from the national mortality register . Results : Mean length of follow up was 25.6 years . After adjustment for age and sex , employees with high job strain , a combination of high dem and s at work and low job control , had a 2.2-fold ( 95 % confidence interval 1.2 to 4.2 ) cardiovascular mortality risk compared with their colleagues with low job strain . The corresponding risk ratio for employees with effort-reward imbalance ( low salary , lack of social approval , and few career opportunities relative to efforts required at work ) was 2.4 ( 1.3 to 4.4 ) . These ratios remained significant after additional adjustment for occupational group and biological and behavioural risks at baseline . High job strain was associated with increased serum total cholesterol at the 5 year follow up . Effort-reward imbalance predicted increased body mass index at the 10 year follow up . Conclusions : High job strain and effort-reward imbalance seem to increase the risk of cardiovascular mortality . The evidence from industrial employees suggests that attention should be paid to the prevention of work stress OBJECTIVE The aim of this study was to evaluate the long-term effects of stress on changes in health behaviour and cardiac risk profile in men and women . DESIGN A prospect i ve cohort study . SETTING The Copenhagen City Heart Study , Denmark . SUBJECTS The analyses were based on 7066 women and men from the second ( 1981 - 1983 ) and third ( 1991 - 1993 ) wave of the Copenhagen City Heart Study . All participants were asked questions on stress and health behaviour and they had their weight , height , blood pressure and level of blood lipids measured by trained personnel . MAIN OUTCOME MEASURES Changes in health behaviour ( smoking , physical activity , alcohol consumption , overweight ) and cardiac risk profile ( cholesterol , HDL cholesterol , blood pressure , diabetes ) . RESULTS Individuals with high levels of stress compared to those with low levels of stress were less likely to quit smoking ( OR = 0.58 ; 95 % CI : 0.41 - 0.83 ) , more likely to become physically inactive ( 1.90 ; 1.41 - 2.55 ) , less likely to stop drinking above the sensible drinking limits ( 0.43 ; 0.24 - 0.79 ) , and stressed women were more likely to become overweight ( 1.55 ; 1.12 - 2.15 ) during follow-up . Men and women with high stress were more likely to use antihypertensive medication ( 1.94 ; 1.63 - 2.30 ) , and stressed men were more than two times as likely to develop diabetes during follow-up ( 2.36 ; 1.22 - 4.59 ) . CONCLUSION This longitudinal study supports a causal relation between stress and cardiovascular diseases mediated through unfavourable changes in health behaviour and cardiac risk profile OBJECTIVE : To study how stress , life satisfaction and personality related factors , are related to long-term major weight gain . DESIGN : Prospect i ve cohort study , with follow-up by question naire at 6 y and 15 y with a within- study replication . SUBJECTS : 5867 twin pairs aged 18–54 y at baseline , considered as two sets of unrelated individuals in analyses . MAIN OUTCOME MEASURES : Adjusted odds ratios ( OR ) for 10 kg weight gain over 6 y and 15 y. RESULTS : A high level of stress at baseline , was a predictor for major weight gain over 6 y , and this effect was consistent in some groups even over 15 y. Low levels of life satisfaction and high scores for neuroticism , were predictors for weight gain in older women . These effects were consistent , even after adjustments for confounding variables ( education , dieting , smoking , alcohol consumption and pregnancy in women ) . High levels of extroversion showed a trend towards lesser weight gain in younger men . CONCLUSION : Psychological traits did not affect the risk of major long-term weight gain in a uniform fashion . The observed effects of the factors related to psychological health were modest and consistent , but varied by age and gender . Thus , there may be trait-specific effects in selected subgroups of the population that should be further investigated Objective : To evaluate the effect of the dem and -control-support model , the effort-reward imbalance model , and emotional dem and s on smoking , alcohol consumption , physical activity , and body mass index . Methods : This is a 2-year prospect i ve cohort study of 3224 public sector employees . Measures were assessed with question naires . Multiple regression analyses were used to predict changes in lifestyle factors . Results : Low reward predicted smoking , low-decision latitude predicted being inactive , and high dem and s predicted high-alcohol consumption but only for men at follow-up even after controlling for potential confounders . There were no other significant findings in the expected direction except for some of the confounders . Conclusions : We found only limited and inconsistent support for the hypothesis that a poor psychosocial work environment is associated with an adverse lifestyle Using comparative data from five countries , this study investigates the psychometric properties of the effort-reward imbalance ( ERI ) at work model . In this model , chronic work-related stress is identified as non-reciprocity or imbalance between high efforts spent and low rewards received . Health-adverse effects of this imbalance were documented in several prospect i ve and cross-sectional investigations . The internal consistency , discriminant validity and factorial structure of ' effort ' , ' reward ' , and ' overcommitment ' scales are evaluated , using confirmatory factor analysis . Moreover , content ( or external ) validity is explored with respect to a measure of self-reported health . Data for the analysis is derived from epidemiologic studies conducted in five European countries : the Somstress Study ( Belgium ; n = 3796 ) , the GAZEL-Cohort Study ( France ; n = 10,174 ) , the WOLF-Norrl and Study ( Sweden ; n = 960 ) , the Whitehall II Study ( UK ; n = 3697 ) and the Public Transport Employees Study ( Germany ; n = 316 ) . Internal consistency of the scales was satisfactory in all sample s , and the factorial structure of the scales was consistently confirmed ( all goodness of fit measures were > 0.92 ) . Moreover , in 12 of 14 analyses , significantly elevated odds ratios of poor health were observed in employees scoring high on the ERI scales . In conclusion , a psychometrically well-justified measure of work-related stress ( ERI ) grounded in sociological theory is available for comparative socioepidemiologic investigations . In the light of the importance of work for adult health such investigations are crucial in advanced societies within and beyond Europe Objective : Previous research has focused on overall associations between work stress and body mass index ( BMI ) ignoring the possibility that stress may cause some people to eat less and lose weight and others to eat more . Using longitudinal data , we studied whether work stress induced weight loss in lean individuals and weight gain in overweight individuals . Design : Prospect i ve cohort study .Subjects : A total of 7965 British civil servants ( 5547 men and 2418 women ) aged 35–55 at study entry ( The Whitehall II study ) . Measurements : Work stress , indicated by the job strain model and measured as job control , job dem and s and job strain , was assessed at baseline and BMI at baseline and at 5-year follow-up . Results : In men , the effect of job strain on weight gain and weight loss was dependent on baseline BMI ( P⩽0.03 ) . In the leanest quintile ( BMI < 22 kg/m2 ) at baseline , high job strain and low job control were associated with weight loss by follow-up , whereas among those in the highest BMI quintile ( > 27 kg/m2 ) , these stress indicators were associated with subsequent weight gain . No corresponding interaction was seen among women . Conclusion : Inconsistent findings reported by previous studies of stress and BMI have generally been interpreted to indicate the absence of an association . In light of our results , the possibility of differential effects of work stress should also be taken into account The authors prospect ively investigated associations between potentially stressful work characteristics and type 2 diabetes incidence in 62,574 young and middle-aged women , aged 29 - 46 years at baseline in 1993 , from the Nurses ' Health Study II ; 365 cases of type 2 diabetes accrued over 6 years of follow-up . Cox proportional hazards regression was used to simultaneously evaluate associations of hours per week in paid employment , years of rotating night-shift work , and job strain with incidence of type 2 diabetes . In multivariate-adjusted analyses , women working less than 20 hours per week had a lower risk of diabetes ( relative risk = 0.80 , 95 % confidence interval : 0.50 , 1.30 ) , and those working overtime ( > or = 41 hours/week ) had an elevated risk of diabetes ( relative risk = 1.23 , 95 % confidence interval : 0.98 , 1.55 ) compared with women working 21 - 40 hours/week ( referent ) in paid employment ( p(trend ) = 0.03 ) . In subsequent analysis , the elevated association appeared stronger in unmarried women ( p(interaction ) = 0.02 ) . A positive association between years in rotating night-shift work and diabetes was mediated entirely by body weight . Job strain was unrelated to risk of type 2 diabetes . In conclusion , working overtime predicted a slightly elevated risk of type 2 diabetes in young and middle-aged female nurses OBJECTIVES : To ascertain the effects of overtime and psychosocial job conditions on the occurrence of non-insulin dependent diabetes mellitus ( NIDDM ) in Japan . DESIGN : An eight year prospect i ve cohort study . SETTING : An electrical company in Japan . PARTICIPANTS : In 1984 , a mailed question naire was sent to industrial workers of an electrical company in Japan . After excluding those who had a history of diabetes mellitus or other chronic diseases , 2597 male respondents were prospect ively followed up for the succeeding eight years . Data from 2194 ( 84 % ) who were completely followed up were analysed . The occurrence of NIDDM during the follow up period was assessed according to the WHO criteria on the basis of an annual screening programme . MAIN RESULTS : The age adjusted incidence of NIDDM was significantly higher in those who worked overtime more than 50 hours per month than in those who worked 25 hours or less per month ( p < 0.05 ) . It was significantly higher in those who worked with new technology at baseline than in those who did not ( p < 0.05 ) . Cox 's proportional hazard model indicated that those who worked overtime more than 50 hours per month had 3.7 times higher risk of NIDDM after controlling for known risk factors ( p < 0.01 ) and those who worked with new technology had 2.4 times higher risk of NIDDM ( p < 0.05 ) . CONCLUSIONS : It is suggested that longer overtime and use of new technology are risk factors of NIDDM in Japanese men An association between psychological factors and diabetes has been suspected for a long time . However , epidemiological data on this association is limited . We investigated the association between psychological factors ( perceived mental stress and type A behavior ) and the onset of diabetes in a community-based , prospect i ve cohort study in a large number of middle-aged Japanese adults . A total of 55,826 subjects ( 24,826 men and 31,000 women ) aged 40 - 69 years were followed for 10 years . A self-administered question naire on medical conditions including diabetes and other lifestyle factors was performed at baseline and 5 and 10 years later . Psychological factors and diabetes were assessed based on the question naire results . During the 10-year follow-up period , we documented 1,601 incident cases ( 6.4 % ) of diabetes among men and 1,093 cases ( 3.5 % ) among women . The risk of diabetes increased with an increasing stress level , especially among men . Multivariate adjusted odds ratios for high stress compared with low stress were 1.36 ( 1.13 to 1.63 ) among men and 1.22 ( 0.98 to 1.51 ) among women . The risk of diabetes increased with an increasing level of type A behavior only among women . Multivariate adjusted odds ratios for high levels of type A behavior compared with low levels of type A behavior were 1.09 ( 0.94 to 1.27 ) among men and 1.22 ( 1.01 to 1.47 ) among women . We found an association between perceived mental stress and the incidence of diabetes , especially among men . We also found an association between type A behavior and the incidence of diabetes among women . In addition , inverse association between coffee consumption and the incidence of diabetes which was consistent with other studies was observed Adverse psychosocial exposures may partially drive the high rates of obesity among blacks . The objective of this study was to prospect ively examine the relationship between perceived psychosocial stress and percent change in BMI among adult black men and women . We used data from 756 women and 416 men who were participants in the Pitt County Study , a community-based , prospect i ve cohort study of blacks in eastern North Carolina . Participants were aged 25 - 50 years of age on entry into the study in 1988 and follow-up was obtained in 2001 . Using multivariable linear regression , we calculated the adjusted mean percentage change in BMI over the follow-up period for each tertile of baseline measures of the Perceived Stress Scale ( low , medium , and high ) , adjusted for potential confounders . For black women , higher levels of psychosocial stress at baseline predicted higher adjusted percentage increase in BMI over the 13-year follow-up : low stress 12.0 % ( 95 % CI 9.6 - 14.4 ) , medium stress 16.3 % ( 95 % CI 13.7 - 18.9 ) , and high stress 15.5 % ( 95 % CI 13.1 - 17.8 ) . For black men , perceived stress was not associated with percent BMI change . These data suggest that interventions targeting obesity in black women should consider the potential impact of emotional stress on weight change Background Job strain ( high dem and s and low decision latitude ) has been associated with hypertension and cardiovascular disease , especially in men . Most studies on job strain and hypertension have been cross-sectional , and prospect i ve data are inconsistent . Objective To prospect ively describe the effects of different psychosocial work characteristics on office blood pressure changes . Methods In total , 448 men and women , mean age 55 years , were followed for a mean of 6.5 years . At baseline , work characteristics and cardiovascular risk factors were assessed . Only employed subjects aged 63 years or younger were eligible for participation . Results Men with baseline job strain had a significantly greater increase in both systolic blood pressure ( 7.7 mmHg , P = 0.02 ) , and diastolic blood pressure ( 5.6 mmHg , P = 0.003 ) , compared to the group with low work dem and s and high decision latitude ( ‘ relaxed ’ ) . These findings were significant also after adjustments for age , follow-up time , baseline blood pressure , blood pressure treatment at baseline and follow-up , and length of education . Work dem and s were more strongly correlated with blood pressure increase than decision latitude . For women , no significant associations between psychosocial work characteristics and blood pressure changes were found , apart from a weak trend of association between increasing decision latitude and increasing blood pressure . Conclusion Job strain significantly predicts an increase in office blood pressure in middle-aged men , but not in women . Work dem and s were more strongly correlated with blood pressure increase than decision latitude in men Psychosocial work stress has been linked to higher risk of type 2 diabetes ( T2DM ) , with the effect being consistently higher among women than men . Also , work stress has been linked to prospect i ve weight gain among obese men but weight loss among lean men . Here , we aim ed to examine the interaction between work stress and obesity in relation to T2DM risk in a gender-specific manner . We studied 5,568 white middle-aged men and women in the Whitehall II study , who were free from diabetes at analysis baseline ( 1993 ) . After 1993 , diabetes was ascertained at six consecutive phases by an oral glucose tolerance test supplemented by self-reports . Cox regression analysis was used to assess the association between job strain ( high job dem and s/low job control ) and 18-year incident T2DM stratifying by BMI ( BMI < 30 kg/m(2 ) vs. BMI ≥30 kg/m(2 ) ) . Overall , work stress was associated with incident T2DM among women ( hazard ratio ( HR ) 1.41 : 95 % confidence intervals : 1.02 ; 1.95 ) but not among men ( HR 0.87 : 95 % confidence interval 0.69 ; 1.11 ) ( P(INTERACTION ) = 0.017 ) . Among men , work stress was associated with a lower risk of T2DM in nonobese ( HR 0.70 : 0.53 ; 0.93 ) but not in obese individuals ( P(INTERACTION ) = 0.17 ) . Among women , work stress was associated with higher risk of T2DM in the obese ( HR 2.01 : 1.06 ; 3.92 ) but not in the nonobese ( P(INTERACTION ) = 0.005 ) . Gender and body weight status play a critical role in determining the direction of the association between psychosocial stress and T2DM . The potential effect-modifying role of gender and obesity should not be ignored by future studies looking at stress-disease associations |
12,183 | 27,346,998 | Other positive correlations between DHEA-S and working memory , attention and verbal fluency were found only in women .
The DHEA effect on cognition is limited to one study conducted among young men with high-doses | UNLABELLED To present a review of cross-sectional and longitudinal studies that investigate the relationship between the hormones Dehydroepi and rosterone ( DHEA ) and Dehydroepi and rosterone sulfate ( DHEA-S ) and cognition . | The objective of this study was to investigate the relation between the peripheral concentrations of the adrenal steroid hormones cortisol and dehydroepi and rosterone sulfate ( DHEAS ) and cognitive impairment and decline . A prospect i ve study design was used . The setting was a suburb of Rotterdam , The Netherl and s. The study population consisted of a sample of 189 healthy participants from the population -based Rotterdam Study , aged 55 - 80 yr , who were invited for an additional examination . Follow-up examinations took place 1.9 yr after baseline , on the average . We determined fasting blood levels of DHEAS before dexamethasone administration and of cortisol and corticosteroid-binding globulin before and after the administration of 1 mg dexamethasone overnight . The 30-point Mini-Mental State Examination ( MMSE ) was used to assess cognition . The associations with cognitive impairment ( MMSE score of < 26 ; 6 % of the sample ) and cognitive decline ( drop in MMSE score of > 1 point/yr ; 24 % ) were estimated using logistic regression , with adjustment for age , sex , education , and depressive symptoms . An increase of 1 SD in the estimate of free cortisol ( SD = 30.3 ) was associated with cognitive impairment , although not significantly [ odds ratio ( OR ) = 1.5 ; 95 % confidence interval ( CI ) , 0.9 - 2.4 ] . A 1 SD increase in the natural logarithm of cortisol after the administration of 1 mg dexamethasone ( SD = 0.68 ) was associated with an OR for cognitive decline of 1.5 ( 95 % CI , 1.0 - 2.3 ) . A 1 SD increase in DHEAS ( SD = 2.10 micromol/L ) was inversely , but nonsignificantly , related to cognitive impairment ( OR = 0.5 ; 95 % CI , 0.2 - 1.1 ) and cognitive decline ( OR = 0.6 ; 95 % CI , 0.4 - 1.1 ) . The ratio of free cortisol over DHEAS was significantly related to cognitive impairment ( OR = 1.8 ; 95 % CI , 1.0 - 3.2 ) . This prospect i ve study among healthy elderly subjects suggested that basal free cortisol levels were positively related to cognitive impairment , and cortisol levels after dexamethasone treatment were related to cognitive decline . There was an inverse , but nonsignificant , association between DHEAS and cognitive impairment and decline BACKGROUND In humans , concentrations of the adrenal steroid hormone dehydroepi and rosterone ( DHEA ) and its sulfate ester ( DHEAS ) decline with age . Results from studies in rodents have suggested that DHEA administration can improve memory performance as well as neuronal plasticity . However , a first study from our laboratory could not demonstrate beneficial effects of DHEA substitution on cognitive performance and well-being in elderly subjects . To further evaluate whether DHEA replacement has effects on the central nervous system , an experiment using event-related potentials ( ERPs ) was conducted . METHODS In this placebo-controlled crossover study , 17 elderly men ( mean age , 71.1 + /- 1.7 yr ; range 59 - 81 yr ) took placebo or DHEA ( 50 mg/day ) for 2 weeks ( double blind ) . After each treatment period subjects participated in an auditory oddball paradigm with three oddball blocks . In the first two blocks subjects had to count the rare tone silently , whereas , in the third block they had to press a button . In addition , memory tests assessing visual , spatial , and semantic memory as well as question naires on psychological and physical well-being were presented . RESULTS Baseline DHEAS levels were lower compared with young adults . After 2-week DHEA replacement , DHEAS levels rose 5-fold to levels observed in young men . DHEA substitution modulated the P3 component of the ERPs , which reflects information updating in short-term memory . P3 amplitude was increased after DHEA administration , and only selectively in the second oddball block . DHEA did not influence P3 latency . Moreover , DHEA did not enhance memory or mood . CONCLUSIONS A 2-week DHEA replacement in elderly men results in changes in electrophysiological indices of central nervous system stimulus processing if the task is performed repeatedly . However , these effects do not appear to be strong enough to improve memory or mood Dehydroepi and rosterone ( DHEA ) and its sulfate form ( DHEAS ) have been the focus of considerable publicity because of their demonstrated associations with a broad range of health outcomes . Yet , knowledge about the effects of endogenous DHEA(S ) on health in humans is limited and often inconclusive , largely because few of the studies have been based on prospect i ve surveys of population -representative sample s. This analysis uses a national longitudinal survey in Taiwan to investigate whether DHEAS is associated with subsequent changes ( 2000 - 2003 ) in functional limitations , cognitive impairment , depressive symptoms , and global self-rated health . Regression models based on this older Taiwanese sample show that among men , lower levels of DHEAS are related to declines in mobility and self-assessed health status and increases in depressive symptoms , while both low and very high levels of DHEAS are associated with poor cognitive function . There are no significant associations among women . These findings differ from those in a previous cross-sectional analysis based on the Taiwan study and underscore the importance of using prospect i ve data to examine the effects of DHEAS on health . The evidence based on this and other longitudinal studies suggests that endogenous DHEAS is related to health outcomes for men , but not women , in both Western and non-Western population This study explores the potential relationship between a series of cognitive abilities and testosterone , dehydroepi and rosterone ( DHEA ) , and rostenedione , and body mass index ( BMI ) measurements in 5-year-old children . 60 boys and 69 girls were administered a test ( K-BIT ) which provided measurements of fluid intelligence ( Matrices subtest ) , crystallized intelligence ( Vocabulary subtest ) , and IQ composite ( the combination of the two subtests ) ; a sub- sample of 48 boys and 61 girls was also subjected to diverse tests related to theory of mind ( affective labeling , appearance-reality distinction , display rules , and false belief ) . Testosterone , DHEA , and and rostenedione levels were measured using an enzyme immunoassay technique in saliva sample s. An analysis of variance failed to reveal any significant differences between boys and girls in any of the cognitive abilities assessed . The correlation analysis revealed a positive relationship between fluid intelligence and testosterone levels in boys , a negative relationship between crystallized intelligence and and rostenedione levels in girls , and between affective labeling and and rostenedione levels in boys . A multiple regression analysis indicated that and rostenedione and BMI were the best predictors for some of the cognitive abilities assessed The levels of dehydroepi and rosterone ( DHEA ) and its sulfate ester DHEAS decrease with age after a peak around 25 yr . Animal studies as well as the first studies in humans have generated the idea that DHEA replacement in elderly subjects may have beneficial effects on well-being and cognitive functions . In the present experiment 40 healthy elderly men and women ( mean age , 69 yr ) participated in a double blind , placebo-controlled DHEA substitution study . For 2 weeks subjects took 50 mg DHEA daily , followed by a 2-week wash-out period and a 2-week placebo period . The treatment sequence was r and omized in a cross-over design . After 2 weeks of DHEA or placebo , psychological and physical well-being as well as cognitive performance were assessed using several question naires and neuropsychological tests . All subjects had low DHEAS baseline levels . DHEA substitution lead to a 5-fold increase in DHEAS levels in women ( from 0.67 + /- 0.1 to 4.1 + /- 0.4 micrograms/mL ; P < 0.001 ) and men ( from 0.85 + /- 0.1 to 4.5 + /- 0.4 micrograms/mL ; P < 0.001 ) . DHEA , and rostenedione , and testosterone levels also increased significantly in both sexes ( all P < 0.001 ) . No significant changes were observed in insulin-like growth factor I or insulin-like growth factor-binding protein-3 levels . DHEA replacement had no strong beneficial effect on any of the measured psychological or cognitive parameters . Only women tended to report an increase in well-being ( P = 0.11 ) and mood ( P = 0.10 ) , as assessed with question naires . They also showed better performance in one of six cognitive tests ( picture memory ) after DHEA . However , after Bonferroni alpha adjustment , this difference was no longer significant . No such trend was observed in men ( P > 0.20 ) . Likewise , no beneficial effects of DHEA substitution could be observed in any of the other tests of the neuropsychological test battery in either sex ( all P > 0.20 ) . In conclusion , the present data do not support the idea of strong beneficial effects of a physiological DHEA substitution on well-being or cognitive performance in healthy elderly individuals BACKGROUND The observation that dehydroepi and rosterone ( DHEA ) concentrations decrease markedly with age has led to the hypothesis that declining DHEA concentrations may contribute to age-related changes in cognition . In the United States , DHEA is widely available as an over-the-counter supplement that individuals are using in an effort to ameliorate age-related cognitive and physical changes . OBJECTIVE To investigate the relationship between age-associated decreases in endogenous DHEA sulfate ( DHEA-S ) concentrations and declines in neuropsychological performance in a prospect i ve , longitudinal study . METHODS The subjects were 883 men from a community-dwelling volunteer sample in the Baltimore Longitudinal Study of Aging . The men were aged 22 to 91 years at the initial visit , and they were followed up for as long as 31 years ( mean , 11 . 55 years ) , with biennial re assessment s of multiple cognitive domains and contemporaneous measurement of serum DHEA-S concentrations . Outcome measures were the results of cognitive tests of verbal and visual memory , 2 tests of mental status , phonemic and semantic word fluency tests , and measures of visuomotor scanning and attention . Serum DHEA-S concentrations were determined by st and ard radioimmunoassay . RESULTS Neither the rates of decline in mean DHEA-S concentrations nor the mean DHEA-S concentrations within individuals were related to cognitive status or cognitive decline . A comparison between the highest and lowest DHEA-S quartiles revealed no cognitive differences , despite the fact that these groups differed in endogenous DHEA-S concentration by more than a factor of 4 for a mean duration of 12 years . CONCLUSION Our longitudinal results augment those of previous prospect i ve studies by suggesting that the decline in endogenous DHEA-S concentration is independent of cognitive status and cognitive decline in healthy aging men Dehydroepi and rosterone ( DHEA ) and its sulfate , DHEA-S , are plentiful adrenal steroid hormones that decrease with aging and may have significant neuropsychiatric effects . In this study , six middle-aged and elderly patients with major depression and low basal plasma DHEA f1p4or DHEA-S levels were openly administered DHEA ( 30 - 90 mg/d x 4 weeks ) in doses sufficient to achieve circulating plasma levels observed in younger healthy individuals . Depression ratings , as well as aspects of memory performance significantly improved . One treatment-resistant patient received extended treatment with DHEA for 6 months : her depression ratings improved 48 - 72 % and her semantic memory performance improved 63 % . These measures returned to baseline after treatment ended . In both studies , improvements in depression ratings and memory performance were directly related to increases in plasma levels of DHEA and DHEA-S and to increases in their ratios with plasma cortisol levels . These preliminary data suggest DHEA may have antidepressant and promemory effects and should encourage double-blind trials in depressed patients There are few reported data on biochemical and functional correlates of and rogen levels in African-American men . This study aim ed at reporting physical and biochemical correlates of serum total testosterone ( total T ) , bioavailable testosterone ( BT ) and dehydroepi and rosterone-sulphate ( DHEAS ) levels in community-dwelling , African-American men aged 50 - 65 years . Home-based physical examinations and health status question naires were administered to r and omly sample d men . Body composition ( dual-energy X-ray absorptiometry ) , lower limb and h and -grip muscle strength , and neuropsychological functions were assessed . Levels of serum total T , BT , DHEAS , oestradiol ( E2 ) , adiponectin , leptin , triglycerides and glucose were measured . Multiple linear regression models were constructed to identify factors independently associated with and rogen levels . DHEAS levels declined from age 50 to 65 years ( p < 0.0001 ) , but total T and BT levels remained constant . Independent of other associated factors , higher total T levels were associated with lower serum triglyceride levels ( beta = -0.142 , p = 0.049 ) ; higher BT was associated with better performance on the trail-making tests ( TMT-B : TMT-A ratio : beta = -0.118 , p = 0.024 ) and higher DHEAS levels were associated with lower adiponectin ( beta = -0.293 , p = 0.047 ) and higher mini-mental state examination ( MMSE ) score ( beta = 0.098 , p = 0.008 ) . Multiple regression models predicted 21 , 18 and 29 % of variance in total T , BT and DHEAS , respectively . Higher total T levels were associated with serum metabolic markers , particularly lower triglycerides , whereas higher BT was associated with better cognitive and muscle function and DHEAS with lower adiponectin and higher MMSE scores OBJECTIVES To examine the effects of dehydroepi and rosterone ( DHEA ) supplementation on cognitive function and quality of life in healthy older adults . DESIGN Double-blind , r and omized , controlled clinical trial . SETTING Clinical research facility . PARTICIPANTS One hundred ten men and 115 women aged 55 to 85 ( mean + /- st and ard deviation 68 + /- 8) . INTERVENTION Fifty milligrams daily oral DHEA versus placebo for 1 year . MEASUREMENTS Six cognitive function tests at baseline and 12 months , the Beck Depression Inventory ( BDI ) , the Medical Outcomes Study 36-item Short Form Survey ( SF-36 ) , the Life Satisfaction Index-Z , the Satisfaction with Life Scale , the Female Sexual Function Index ( in women ) , and the 15-item International Index of Erectile Function ( in men ) at baseline and 3 , 6 , and 12 months . RESULTS There were no differences between the DHEA and placebo groups in change over time in cognitive function ( P>.10 ) . Over time , BDI scores decreased for men ( P=.006 ) and women ( P=.02 ) , and Satisfaction with Life Scale scores increased for women ( P=.004 ) , but there were no differences between the DHEA and placebo groups over time on these measures or the SF-36 , Life Satisfaction Index-Z scale , or sexual function scales ( P>.10 ) . CONCLUSION DHEA supplementation has no benefit on cognitive performance or well-being in healthy older adults , and it should not be recommended for that purpose in the general population Rationale Dehydroepi and rosterone ( DHEA ) has been reported to enhance cognition in rodents , although there are inconsistent findings in humans . Objectives The aim of this study was to investigate the effects of DHEA administration in healthy young men on episodic memory and its neural correlates utilising an event-related potential ( ERP ) technique . Methods Twenty-four healthy young men were treated with a 7-day course of oral DHEA ( 150 mg b.d . ) or placebo in a double blind , r and om , crossover and balanced order design . Subjective mood and memory were measured using visual analogue scales ( VASs ) . Cortisol concentrations were measured in saliva sample s. ERPs were recorded during retrieval in an episodic memory test . Low-resolution brain electromagnetic tomography ( LORETA ) was used to identify brain regions involved in the cognitive task . Results DHEA administration led to a reduction in evening cortisol concentrations and improved VAS mood and memory . Re collection accuracy in the episodic memory test was significantly improved following DHEA administration . LORETA revealed significant hippocampal activation associated with successful episodic memory retrieval following placebo . DHEA modified ERPs associated with retrieval and led to a trend towards an early differential activation of the anterior cingulate cortex ( ACC ) . Conclusions DHEA treatment improved memory re collection and mood and decreased trough cortisol levels . The effect of DHEA appears to be via neuronal recruitment of the steroid sensitive ACC that may be involved in pre-hippocampal memory processing . These findings are distinctive , being the first to show such beneficial effects of DHEA on memory in healthy young men A major achievement from 500 million years of evolution is the establishment of a high secretion rate of dehydroepi and rosterone ( DHEA ) by the human adrenal gl and s coupled with the indroduction of menopause which stops secretion of estrogens by the ovary . Cessation of estrogen secretion at menopause eliminates the risks of endometrial hyperplasia and cancer which would result from non-opposed estrogen stimulation during the post-menopausal years . In fact , from the time of menopause , DHEA becomes the exclusive and tissue-specific source of sex steroids for all tissues except the uterus . Intracrinology , a term coined in 1988 , describes the local formation , action and inactivation of sex steroids from the inactive sex steroid precursor DHEA . Over the past 25 years most , if not all , the genes encoding the human steroidogenic and steroid-inactivating enzymes have been cloned and sequenced and their enzymatic activity characterized . The problem with DHEA , however , is that its secretion decreases from the age of 30 years and is already decreased , on average , by 60 % at time of menopause . In addition , there is a large variability in the circulating levels of DHEA with some post-menopausal women having barely detectable serum concentrations of the steroid while others have normal values . Since there is no feedback mechanism controlling DHEA secretion within ' normal ' values , women with low DHEA will remain with such a deficit of sex steroids for their remaining lifetime . Since there is no other significant source of sex steroids after menopause , one can reasonably believe that low DHEA is involved , in association with the aging process , in a series of medical problems classically associated with post-menopause , namely osteoporosis , muscle loss , vaginal atrophy , fat accumulation , hot flashes , skin atrophy , type 2 diabetes , memory loss , cognition loss and possibly Alzheimer 's disease . A recent r and omized , placebo-controlled study has shown that all the signs and symptoms of vaginal atrophy , a classical problem recognized to be due to the hormone deficiency of menopause , can be rapidly improved or corrected by local administration of DHEA without systemic exposure to estrogens . In addition , the four domains of sexual dysfucntion are improved . For the other problems of menopause , although similar large scale , r and omized and placebo-controlled studies usually remain to be performed , the available evidence already strongly suggests that they could be improved , corrected or even prevented by exogenous DHEA . In men , the contribution of adrenal DHEA to the total and rogen pool has been measured at 40 % in 65 - 75-year-old men . Such data stress the necessity of blocking both the testicular and adrenal sources of and rogens in order to achieve optimal benefits in prostate cancer therapy . On the other h and , the comparable decrease in serum DHEA levels observed in both sexes has less consequence in men who continue to receive a practically constant supply of testicular sex steroids during their whole life . In fact , in men , the appearance of hormone-deficiency symptoms common to women is observed at a later age and with a lower degree of severity . Consequently , DHEA replacement has shown much more easily measurable beneficial effects in women . Most importantly , despite the non-scientific and unfortunate availability of DHEA as a food supplement in the United States , a situation that discourages rigorous clinical trials on the crucial physiological and therapeutic role of DHEA , no serious adverse event related to DHEA has ever been reported in the world literature ( thous and s of subjects exposed ) or in the monitoring of adverse events by the FDA ( millions of subjects exposed ) , thus indicating , as expected from its known physiology , the excellent safety profile of DHEA . With today 's knowledge , one can reasonably suggest that DHEA offers the promise of a safe and efficient replacement therapy for the multiple problems related to hormone deficiency after menopause without the risks associated with estrogen-based or any other treatments BACKGROUND Though among the most abundant human steroid hormones , the physiologic role of dehydroepi and rosterone and its sulfate ( DHEAS ) is not known . Our goal was to determine if DHEAS is associated with cognition and mood in older women , and if baseline DHEAS levels are predictive of cognitive decline . METHODS In a prospect i ve cohort , we studied 394 r and omly selected community-dwelling women , aged 65 years or older , currently enrolled in the Study of Osteoporotic Fractures . Subjects were administered a modified Mini-Mental State Exam , Trials B , Digit Symbol , and the Geriatric Depression Scale-Shortened ( GDSS ) , at study onset and 4 - 6 years later . Serum was obtained at study initiation for DHEAS analysis . RESULTS DHEAS levels declined with age , as expected . There was no consistent association of DHEAS quartile or log DHEAS with any of the four outcomes , even after multivariate adjustment . Change in cognitive performance overtime was not associated with DHEAS levels . Analysis of the 32 women without any detectable DHEAS compared to those with detectable levels revealed higher measures on the GDSS ( mean score 3.4 + /- 3.6 compared with 1.6 + /- 2.3 , p = .028 ) and a higher percentage with depression ( 21.7 % compared with 4.6 % , p = .001 ) . CONCLUSIONS Serum DHEAS is not a sensitive predictor of cognitive performance or decline on a selected neuropsychological battery in elderly community women ; however , nondetectable levels may be associated with depression In a cross-sectional study , serum dehydroepi and rosterone sulfate ( DS ) concentrations were measured in 981 men and 481 women , aged 11 - 89 , yr . The result ing data were asymetrically distributed and were normalized by logarithmic transformation and analyzed by 5-yr age grouping ( e.g. 15 - 19 yr , 20 - 24 yr , etc . ) . The DS concentration peaked at age 20 - 24 yr in men ( logarithmic mean , 3470 ng/ml ) and at age 15 - 19 yr in women ( log mean , 2470 ng/ml ) . Mean values then declined steadily in both sexes ( log mean at greater than 70 yr of age , 670 ng/ml in men and 450 ng/ml in women ) and were significantly higher in men than women at ages from 20 - 69 yr . Analysis of 517 r and omly selected sera ( from women ) which had been stored frozen for 10 - 15 yr gave results indistinguishable from values obtained from fresh specimens . In a supplementary study , a longitudinal analysis of weekly specimens from 4 normal men , aged 36 - 59 yr , revealed individual variability ( mean coefficient of variation , 19 % ) and failed to demonstrate any monthly , seasonal , or annual rhythmicity . Based on the above analyses , a table of normal serum DS ranges for adult men and women is presented for use as a clinical reference Dehydroepi and rosterone ( DHEA ) is a steroid that shows a marked age-related decline in humans . Previous research suggests potential for DHEA replacement in old age to enhance cognition and well-being . We conducted a clinical trial to test these hypotheses in a non- clinical sample of 46 men aged 62 - 76 . Participants received either 50 mg DHEA daily for 13 weeks , followed by placebo for 13 weeks , or the reverse , in a r and omised double-blind cross-over trial design . Levels of salivary cortisol and DHEA were measured at 0800 h and 2000 h prior to each assessment session . Cognition was assessed with tests of speed , attention and episodic memory . Well-being was measured with question naires of mood and perceived health . Mood question naires were completed at the assessment session as well as concurrently with saliva sampling . A correlational analysis of baseline behavioural data with hormonal data , controlling for age , revealed that higher morning DHEA was associated with lower confusion ( r=-0.33 ; P=0.04 ) , while higher evening DHEA was associated with lower anxiety ( r=-0.35 ; P=0.03 ) and lower current negative mood in the morning ( r=-0.37 ; P=0.03 ) . Conversely , higher morning cortisol and a morning cortisol/DHEA ratio were associated with higher anxiety ( r=0.35 ; P=0.03 ) , ( r=0.46 ; P=0.004 ) , general mood disturbance ( r=0.32 ; P=0.046 ) , ( r=0.32 ; P=0.04 ) and higher current negative mood in the evening ( r=0.37 ; P=0.03 ) , ( r=0.38 ; P=0.03 ) . A higher morning cortisol/DHEA ratio was also associated with higher confusion ( r=0.39 ; P=0.01 ) and lower visuo-spatial memory performance ( r=-0.39 ; P=0.01 ) . Unexpectedly , higher evening cortisol was associated with faster choice reaction time ( r=-0.33 ; P=0.04 ) . These findings are consistent with an impairing effect of high cortisol on episodic memory and mood in older men , which may be attenuated by DHEA . When treatment effects were analysed , no significant effects of DHEA were observed on any of the trial outcomes , providing no support for benefits of DHEA supplementation for cognition or well-being in normal older men in the shorter-term Men ( n = 31 ) , women estrogen-users ( n = 14 ) , and women estrogen non-users ( n = 41 ) , whose average age was 72.1 + /- 5.6 years , were tested with a battery of psychological tests measuring verbal memory , visual memory , concentration and attention , language fluency and semantic memory , and mood . Plasma levels of testosterone ( T ) , estradiol ( E2 ) , cortisol ( CRT ) and dehydroepi and rosterone-sulfate ( DHEAS ) were assessed by radioimmunoassay . The ratio of DHEAS to CRT was calculated to determine it 's relationship to memory functioning . The men had higher T and DHEAS levels than both groups of women . Women estrogen-users had higher E2 levels than both men and estrogen non-users and the men had higher E2 levels and a higher DHEAS/CRT ratio than the estrogen non-users . There were no group differences in CRT levels . Men and estrogen-users had higher total ( p < .01 ) and forward ( p < .001 ) digit span scores compared with non-users . Women estrogen-users also had higher backward digit span scores than non-users ( p < .05 ) , while both groups of women performed better than men on category retrieval ( p < .01 ) . The implication s of these findings with respect to hormonal influences on memory in elderly men and women are discussed |
12,184 | 23,529,742 | There was heterogeneity in the leg pain intensity and ODI results and improvements were no longer statistically significant when studies were restricted to RCTs .
There was a reduction in the need for discectomy , which was not statistically significant , and no difference in the number of adverse effects . | Purpose Systematic review comparing biological agents , targeting tumour necrosis factor α , for sciatica with placebo and alternative interventions . | Study Design . A r and omized controlled trial . Objectives . To evaluate the efficacy of infliximab , a monoclonal antibody against tumor necrosis factor (TNF)-&agr ; in a r and omized controlled setting . Summary of Background Data . Recently , we obtained encouraging results in an open-label study of infliximab in patients with disc herniation-induced sciatica . Furthermore , the results of experimental studies support the use of infliximab in sciatica . Therefore , we initiated a r and omized , controlled trial ( FIRST II , Finnish Infliximab Related STudy ) to confirm the efficacy of a single infusion of infliximab for sciatic pain . Methods . Inclusion criteria were unilateral moderate to severe sciatic pain with an MRI-confirmed disc herniation concordant with the symptoms and signs of radicular pain . Patients had to be c and i date s for discectomy , as evaluated by an independent orthopedic surgeon . Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo . Assessment s at baseline and various time points included clinical examination with measurement of straight leg raising restriction ; question naires related to subjective symptoms ( leg and back pain by 100-mm visual analog scale , Oswestry disability ) ; sick leaves ; number of discectomies ; and adverse effects possibly related to treatment . The primary endpoint was a reduction in leg pain from baseline to 12 weeks , which was analyzed using a Mann-Whitney U test and repeated- measures analysis . Results . A significant reduction in leg pain was observed in both groups , with no significant difference between treatment regimens . Similar efficacy was observed between treatment groups for secondary endpoints . Seven patients in each group required surgery . No adverse effects related to treatment were encountered . Conclusions . The results of this r and omized trial do not support the use of infliximab for lumbar radicular pain in patients with disc herniation-induced sciatica Study Design . An open-label trial . Objectives . To test the long-term efficacy of infliximab , a monoclonal antibody against tumor necrosis factor-alpha ( TNF-α ) , in disc herniation-induced sciatica . Summary of Background Data . Our recent trial indicated that a single infusion of 3 mg/weight-kg of infliximab produced a rapid curative effect in disc herniation-induced sciatica . Here , we describe the 1-year effect of a 3 mg/kg of infliximab in these 10 patients and our experience with a lower dose of 1 mg/kg of infliximab for the same indication in 2 additional patients . Methods . Patients with severe sciatica were treated with a single infusion of infliximab , 3 mg/weight-kg in 10 patients and 1 mg/kg in 2 patients , intravenously over 2 hours . The outcomes ( leg and back pain on a 100-mm visual scale , Oswestry disability , clinical signs ) were assessed at 1 week , 2 weeks , 1 month , 3 months , 6 months , and 1 year after the infusion . The outcomes with 3 mg/kg of infliximab were compared to 62 patients who received periradicular saline for sciatica in a previous trial . The resorption rate of disc herniations from baseline to 1 year was compared between infliximab and control groups . Results . The response to 1 mg/kg of infliximab for leg pain was good only in 1 of the 2 patients treated , whereas the response to 3 mg/kg of infliximab for leg pain was sustained in most patients over the 1-year follow-up . The 1-year response significantly favored 3 mg/kg of infliximab over periradicular saline in leg pain ( P = 0.005 ) and disability ( P = 0.003 ) . Neurologic abnormalities normalized more comprehensively in the infliximab group ( P = 0.001 ) . Reduction in disc herniation volume did not differ between the infliximab-treated patients and controls . Conclusions . The results showed that the beneficial effect of a single infusion of 3 mg/kg of infliximab for herniation-induced sciatica is sustained in most patients over a 1-year follow-up period . Furthermore , infliximab does not seem to interfere with the spontaneous resorption of disc herniations Policy decisions often require synthesis of evidence from multiple sources , and the source studies typically vary in rigour and in relevance to the target question . We present simple methods of allowing for differences in rigour ( or lack of internal bias ) and relevance ( or lack of external bias ) in evidence synthesis . The methods are developed in the context of reanalysing a UK National Institute for Clinical Excellence technology appraisal in antenatal care , which includes eight comparative studies . Many were historically controlled , only one was a r and omized trial and doses , population s and outcomes varied between studies and differed from the target UK setting . Using elicited opinion , we construct prior distributions to represent the biases in each study and perform a bias-adjusted meta- analysis . Adjustment had the effect of shifting the combined estimate away from the null by approximately 10 % , and the variance of the combined estimate was almost tripled . Our generic bias modelling approach allows decisions to be based on all available evidence , with less rigorous or less relevant studies downweighted by using computationally simple methods Study Design . Prospect i ve , double-blind , reference-controlled , investigator-initiated , single center . Objective . To evaluate the efficacy of Autologous Conditioned Serum ( ACS ; Orthokine ) for the treatment of lumbar radicular compression in comparison to triamcinolone . Summary of Background Data . Evidence from animal studies indicates that cytokines such as interleukin-1 play a decisive role in the pathophysiology of lumbar radiculopathy . ACS is enriched in the interleukin-1 receptor antagonist and other anti-inflammatory cytokines . Methods . Thirty-two patients were treated by epidural perineural injections with ACS ; 27 patients were treated with 5 mg triamcinolone and 25 patients with 10 mg triamcinolone . Treatment was applied once per week for 3 consecutive weeks and followed for 6 months . The Visual Analogue Scale ( VAS ) of low back pain was the primary outcome measure . The Oswestry Disability Index ( ODI ) was the secondary endpoint of the study . All statistical analyses were performed in an exploratory manner using SAS for Windows , version 8.2 , on a personal computer . Descriptive statistics were calculated for the VAS and ODI by treatment group and time point . The data were su bmi tted to a repeated- measurements analysis of variance with effects on treatment group , time , and treatment group-by-time interaction . Results . Patients with lumbar back pain who were treated with ACS or the 2 triamcinolone concentrations showed a clinical ly remarkable and statistically significant reduction in pain and disability , as measured by patient administered outcome measurements . From Week 12 to the final evaluation at Week 22 , injections with ACS showed a consistent pattern of superiority over both triamcinolone groups with regard to the VAS score for pain , but statistical significance was observed only at Week 22 in direct comparison to the triamcinolone 5 group . However , there was no statistically significant difference between the 2 triamcinolone dosages during the 6 months of the study . Conclusion . ACS is an encouraging treatment option for patients with unilateral lumbar radicular compression . The decrease in pain was pronounced , clinical ly remarkable , and potentially superior to steroid injection Background : Recent evidence implicates the inflammatory cytokine tumor necrosis factor as a major cause of radiculopathy . Yet , whereas open-label studies with systemically delivered tumor necrosis factor inhibitors have yielded positive results , a placebo-controlled study failed to demonstrate efficacy . One variable that may have contributed to poor outcomes is low drug levels at the site of nerve inflammation . To date , no studies have evaluated the efficacy or safety of epidurally administered anti-tumor necrosis factor agents . Methods : A double-blind , placebo-controlled , dose-response study was conducted to evaluate an epidural tumor necrosis factor inhibitor . Twenty-four patients with subacute lumbosacral radiculopathy were r and omly assigned to receive two transforaminal epidural injections of 2 , 4 , or 6 mg of entanercept 2 weeks apart in successive groups of eight . In each group , two patients received epidural saline . A parallel epidural canine safety study was conducted using the same injection doses and paradigm as in the clinical study . Results : The animal and human safety studies revealed no behavioral , neurologic , or histologic evidence of drug-related toxicity . In the clinical arm , significant improvements in leg and back pain were collectively noted for the etanercept-treated patients , but not for the saline group , one month after treatment . One patient in the saline group ( 17 % ) , six patients in the 2-mg group ( 100 % ) , and four patients each in the 4-mg and 6-mg groups ( 67 % ) reported at least 50 % reduction in leg pain and a positive global perceived effect one month after treatment . Six months after treatment , the beneficial effects persisted in all but one patient . Conclusion : Epidural entanercept holds promise as a treatment for lumbosacral radiculopathy 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 OBJECTIVES To explore the efficacy of a tumour necrosis factor alpha ( TNFalpha ) inhibitor ( etanercept , Enbrel ) in patients with severe sciatica . METHODS A pilot study of etanercept was conducted in patients admitted to hospital for acute severe sciatica . Ten consecutive patients received three subcutaneous injections of etanercept ( 25 mg every 3 days ) in addition to st and ard analgesia . Response was evaluated at day 10 ( T1 ) and week 6 ( T2 ) using a visual analogue scale for leg pain ( VASL ) and for low back pain ( VASB ) , and two vali date d functional scores : the Oswestry disability index ( ODI ) and the Rol and Morris disability question naire ( RMDQ ) . The control group consisted of 10 patients with severe sciatica , who took part in an observational study on i.v . methylprednisolone . RESULTS In the etanercept group all variables improved : VASB from 36 to 7 ; VASL from 74 to 12 ; RMDQ from 17.8 to 5.8 , and ODI from 75.4 to 17.3 ; all p<0.001 . Pain ( VASL and VASB : p<0.001 ) and ODI ( p<0.05 ) were significantly better in the etanercept group than in the methylprednisolone group . CONCLUSION In this open , historical group controlled study , patients with severe sciatica had sustained improvement after a short treatment with etanercept that was better than st and ard care plus a short course of methylprednisolone . These results suggest that inhibition of TNFalpha is beneficial in the treatment of sciatica and support a pathological role for TNFalpha in the pathogenesis of sciatica . These results need to be confirmed by a r and omised controlled trial To study the natural history of acute sciatica , 208 patients with obvious symptoms and signs of a lumbar radiculopathy ( L5 and S1 ) were examined within 14 days of onset . A concomitant double-blind investigation of the effect of the nonsteroidal anti-inflammatory drug piroxicam was performed . The results measured by visual analog scale and Rol and 's functional tests showed a satisfactory improvement throughout the 4 weeks of observation . The piroxicam-treated group had same results as the control group . Based on question naires at months 3 and 12 approximately 30 % of the patients still complained about back trouble and 19.5 % were out of work after 1 year . Four patients underwent surgery during this period OBJECTIVE Sciatica is thought to have a good clinical outcome , but in fact , its natural history is not well known . STUDY DESIGN AND SETTING We studied a prospect i ve cohort of 3,164 workers from the French national electricity and gas company . In this cohort , 622 subjects suffered from sciatica in 1991 . The predictive factors of the persistence or recurrence of sciatica after 2 years were identified by multivariate analysis ( logistic regression ) . RESULTS Of the 622 subjects with sciatica in 1991 , 55 % still reported its symptoms in 1993 and 53 % in 1995 . Of those who had recovered from sciatica in 1993 , 61 % still had low back pain and 27 % of them long-lasting low back pain in 1993 . The factors predictive of the persistence or recurrence of sciatica in 1993 , identified by multivariate analysis , were : driving at least 2 hr/day , carrying heavy loads at work , a high level of psychosomatic problems , and sciatica symptoms the year before study inclusion . CONCLUSION Recovery from sciatica is less frequent than expected . Attention should be given to occupational and personal factors associated with persistence or recurrence of sciatica Study Design Triple blind r and omized controlled study . Objective To establish the treatment effect of etanercept in acute sciatica secondary to lumbar disc herniation . Summary of Background Data Etanercept is a selective competitor of tumor necrosis factor-α which is a proinflammatory cytokine . It is currently used alone or in combination with other medication for the treatment of chronic inflammatory disease . Methods Inclusion criteria were acute unilateral radicular leg pain secondary to herniated nucleus pulposus confirmed on magnetic resonance imaging scan . Exclusions were previous back surgery , spinal stenosis and any contraindications to the use of etanercept such as immunosuppression . The patient , the injector , and assessor were blinded to the agent being used . Follow-up was at 6 weeks and 3 months posttreatment . Oswestry disability index and visual analog scores were among the assessment criteria . Results Fifteen patients were recruited in a 4 years period with a 3 months follow-up of 80 % . The etanercept group had 8 patients whereas the placebo group had 7 . The average Oswestry disability index for the etanercept group preintervention was higher than that in the placebo group ( 53.6 vs. 50.4 ) and this remained the same after 6 weeks ( 46.1 vs. 31.2 ) and 3 months of follow-up ( 37 vs. 35 ) . Visual analog score was also higher in the etanercept group versus placebo ; preinjection ( 8.6 vs. 7.4 ) , 6 weeks ( 5.0 vs. 3.8 ) , and 3 months ( 4.8 vs. 4.5 ) . Conclusions Small numbers of trial participants limited statistical analysis . The trend appears to show no benefit to the use of etanercept over placebo in the pharmacologic treatment of sciatica Study Design . A r and omized controlled trial . Objectives . To evaluate the long-term efficacy of infliximab , a monoclonal antibody against tumor necrosis factor alpha ( TNF-α ) , in patients with acute/subacute sciatica secondary to herniated disc . Summary of Background Data . The results of experimental studies and our open-label trial support the use of infliximab in sciatica . Here we report the 1-year results of a r and omized controlled trial ( FIRST II , Finnish Infliximab Related STudy ) evaluating the efficacy and safety of a single infusion of infliximab for sciatic pain . Methods . Inclusion criteria were unilateral sciatic pain with a disc herniation concordant with the symptoms and signs of radicular pain . Patients had to be c and i date s for discectomy . Criteria for discectomy included ( in addition to a symptomatic disc herniation on MRI ) neural entrapment ( straight leg raising [ SLR ] ≤60 ° ) with either a short-term ( 2–4 weeks ) severe or long-term ( 4–12 weeks ) moderate leg pain . Forty patients were allocated to a single intravenous infusion of either infliximab 5 mg/kg or placebo . Differences in the clinical examination parameters ( straight leg raise [ SLR ] , muscle strength , sensory defects , tendon reflexes ) , patient-reported symptoms ( leg and back pain using a visual analog scale [ VAS ] , Oswestry disability , quality -of-life [ R AND -36 ] ) , sick leaves , number of discectomies , and adverse effects between the two treatment groups over the 1-year follow-up were compared using Mann-Whitney U test or Student 's t test , repeated- measures analysis , or Cox proportional hazards model . Logistic regression was used to assess the predictors of good response . Results . Sixty-seven percent of patients in the infliximab group reported no pain at 52 weeks compared with 63 % in the control group ( P = 0.72 ) . Similar efficacy was observed between treatment groups for other outcomes . Eight patients in each group required surgery . Three nonserious adverse reactions were encountered in the infliximab group . The response ( irrespective of the treatment ) was significantly better with shorter symptom duration and less SLR restriction at baseline . Patients in the infliximab group appeared to especially benefit in cases of a L4–L5 ( or L3–L4 ) herniation and if a Modic change was colocalized at the symptomatic level . Conclusions . Although the long-term results of this r and omized trial do not support the use of infliximab compared with placebo for lumbar radicular pain in patients with disc herniation-induced sciatica , further study in a subgroup of patients with L4–L5 or L3–L4 herniations , especially in the presence of Modic changes , appears to be warranted Study Design . R and omized , double-blinded clinical trial . Objective . To compare effi cacies of two active therapies for chronic low back pain . Summary of Background Data . Radicular pain may result from intervertebral disc herniation . Clonidine has demonstrated analgesic and anti-infl ammatory activity in animal studies on nerve injury . Extensive clinical experience supports neuraxial clonidine ’s safety . Methods . Patients with approximately 3 months of low back pain and leg pain due to intervertebral disc herniation were r and omized to transforaminal epidural injection(s ) of 2 % lidocaine and either clonidine ( 200 or 400 g ) or triamcinolone ( 40 mg ) . Patients received one to three injections administered at about 2 weeks apart . Patients , investigators , and study coordinators were blinded to the treatment . The primary outcome was an 11-point Pain Intensity Numerical Rating Scale at 1 month . Other outcomes included Patient Global Impression of Change and functional measures . Results . Of the 33 patients screened and r and omized , 26 enrolled , of which 11 received clonidine and 15 triamcinolone . Both groups showed signifi ca nt improvement in pain score at 2 weeks and 1 month compared with baseline ( P 0.05 ) . The corticosteroid group showed additional functional improvement at 1 month with respect to clonidine ( P 0.022 ) . There was no difference between groups for primary outcome . However , as target enrollment was not reached , we can not say with confi dence that the two treatments would be expected to result in similar short-term pain relief . Adverse effects were common in both groups , but there were no serious complications . Conclusions . Radicular pain due to intervertebral disc herniation improved rapidly with transforaminal epidural injection of either clonidine or triamcinolone . Corticosteroid result ed in greater functional improvement , with unclear differences in analgesia . BACKGROUND Perineural inhibitors of tumor necrosis factor have recently generated intense interest as an alternative to epidural steroid injections for lumbosacral radiculopathy . OBJECTIVE To evaluate whether epidural steroids , etanercept , or saline better improves pain and function in adults with lumbosacral radiculopathy . DESIGN A multicenter , 3-group , r and omized , placebo-controlled trial conducted from 2008 to 2011 . R and omization was computer-generated and stratified by site . Pharmacists prepared the syringes . Patients , treating physicians , and nurses assessing outcomes were blinded to treatment assignment . ( Clinical Trials.gov registration number : NCT00733096 ) SETTING Military and civilian treatment centers . PATIENTS 84 adults with lumbosacral radiculopathy of less than 6 months ' duration . INTERVENTION 2 epidural injections of steroids , etanercept , or saline , mixed with bupivacaine and separated by 2 weeks . MEASUREMENTS The primary outcome measure was leg pain 1 month after the second injection . All patients had 1-month follow-up visits ; patients whose condition improved remained blinded for the 6-month study period . RESULTS The group that received epidural steroids had greater reductions in the primary outcome measure than those who received saline ( mean difference , -1.26 [ 95 % CI , -2.79 to 0.27 ] ; P = 0.11 ) or etanercept ( mean difference , -1.01 [ CI , -2.60 to 0.58 ] ; P = 0.21 ) . For back pain , smaller differences favoring steroids compared with saline ( mean difference , -0.52 [ CI , -1.85 to 0.81 ] ; P = 0.44 ) and etanercept ( mean difference , -0.92 [ CI,-2.28 to 0.44 ] ; P = 0.18 ) were observed . The largest differences were noted for functional capacity , in which etanercept fared worse than the other treatments : steroids vs. etanercept ( mean difference , -16.16 [ CI , -26.05 to -6.27 ] ; P = 0.002 ) , steroids vs. saline ( mean difference , -5.87 [ CI , -15.59 to 3.85 ] ; P = 0.23 ) , and etanercept vs. saline ( mean difference , 10.29 [ CI , 0.55 to 20.04 ] ; P = 0.04 ) . More patients treated with epidural steroids ( 75 % ) reported 50 % or greater leg pain relief and a positive global perceived effect at 1 month than those who received saline ( 50 % ) or etanercept ( 42 % ) ( P = 0.09 ) . LIMITATION Short-term follow-up , small sample size , and a possibly subtherapeutic dose of etanercept . CONCLUSION Epidural steroid injections may provide modest short-term pain relief for some adults with lumbosacral radiculopathy , but larger studies with longer follow-up are needed to confirm their benefits . PRIMARY FUNDING SOURCE The John P. Murtha Neuroscience and Pain Institute , International Spinal Intervention Society , and Center for Rehabilitation Sciences Research OBJECTIVE Based on several experimental results and on a preliminary study , a trial was undertaken to assess the efficacy of adalimumab , a tumor necrosis factor alpha inhibitor , in patients with radicular pain due to lumbar disc herniation . METHODS A multicenter , double-blind , r and omized controlled trial was conducted between May 2005 and December 2007 in Switzerl and . Patients with acute ( duration of < 12 weeks ) and severe ( Oswestry Disability Index score of > 50 ) radicular leg pain and imaging-confirmed lumbar disc herniation were r and omized to receive as adjuvant therapy either 2 subcutaneous injections of adalimumab ( 40 mg ) at 7-day intervals or matching placebo . The primary outcome was the score for leg pain , based on a visual analog scale ( 0 - 100 mm ) , which was recorded every day for 10 days and at 6 weeks and 6 months . RESULTS Of the 265 patients screened , 61 were enrolled ; 31 patients were assigned to receive adalimumab , and 4 patients in the placebo group were lost to followup . Over time , the course of leg pain was more favorable in the adalimumab group than in the placebo group ( P = 0.002 ) . However , the effect size was relatively small , and at the last followup visit the difference was 13.8 ( 95 % confidence interval -11.5 , 39.0 ) . Compared with patients in the placebo group , approximately twice as many patients in the adalimumab group fulfilled the criteria for " responders " and for " low residual disease impact " ( P < 0.05 ) , and fewer surgical discectomies were performed ( 6 versus 13 in the placebo group ; P = 0.04 ) . CONCLUSION The addition of a short course of adalimumab to the treatment regimen of patients experiencing acute and severe sciatica result ed in a small decrease in leg pain and in significantly fewer surgical procedures |
12,185 | 28,777,739 | In summary , statin use is associated with a decreased incidence rate of cirrhosis and is most pronounced in Eastern countries but also in Western countries | Hepatitis B and hepatitis C are leading causes of chronic liver disease , particularly cirrhosis .
Recently , several studies have observed that statins have an inverse relationship with cirrhosis in hepatitis B or C patients .
However , no published meta- analysis studied the protective effect of statins on cirrhosis .
Thus , we conducted a systematic review and meta- analysis of published observational studies to better underst and the relationship between statins and the risk of cirrhosis . | BACKGROUND Hepatitis C viral ( HCV ) infection is the leading cause of death due to liver disease in the United States . Currently , pegylated interferon and ribavirin produce sustained viral remission in only 50 % of patients . Additional agents are needed to increase the cure rate . In vitro experiments show strong antiviral effects of fluvastatin against HCV . OBJECTIVES : To assess the safety and antiviral effects of fluvastatin in chronic HCV carriers . METHODS : 31 veterans with chronic HCV were prospect ively given oral doses of fluvastatin , 20 to 320 mg/day , for 2–12 weeks with weekly monitoring of HCV RNA and liver tests . Reductions of viral load ( P < 0.01 ) versus a control group were considered suppressive . RESULTS : With 80 mg a day or less , 11/22 ( 50 % ) patients responded by lowering HCV RNA . The first lowering occurred within 4 weeks ( 9/11 , 82 % ) . The greatest weekly change in HCV RNA level was a 1.75 log10 reduction . When lowered in responders , the viral load remained relatively constant for 2–5 weeks ( 7/9 , 78 % ) , or on the next test rebounded immediately to a non-significant change from , baseline ( n = 2 ) . Continued lowering of virus was seen in 2/19 ( 22 % ) patients when the study ended . We found no evidence of liver tests worsening . CONCLUSIONS : FLV used as monotherapy in vivo showed suppressive effects of HCV clinical ly that are modest , variable , and often short-lived . These findings support “ proof-of-concept ” for pilot trials combining fluvastatin with st and ard therapy . Statins and fluvastatin , in particular , appear to be safe for use in hepatitis BACKGROUND & AIMS Simvastatin improves liver generation of nitric oxide and hepatic endothelial dysfunction in patients with cirrhosis , so it could be an effective therapy for portal hypertension . This r and omized controlled trial evaluated the effects of continuous simvastatin administration on the hepatic venous pressure gradient ( HVPG ) and its safety in patients with cirrhosis and portal hypertension . METHODS Fifty-nine patients with cirrhosis and portal hypertension ( HVPG > or = 12 mm Hg ) were r and omized to groups that were given simvastatin 20 mg/day for 1 month ( increased to 40 mg/day at day 15 ) or placebo in a double-blind clinical trial . R and omization was stratified according to whether the patient was being treated with beta-adrenergic blockers . We studied splanchnic and systemic hemodynamics and variables of liver function and safety before and after 1 month of treatment . RESULTS Simvastatin significantly decreased HVPG ( -8.3 % ) without deleterious effects in systemic hemodynamics . HVPG decreases were observed in patients who were receiving beta-adrenergic blockers ( -11.0 % ; P = .033 ) and in those who were not ( -5.9 % ; P = .013 ) . Simvastatin improved hepatic , fractional , and intrinsic clearance of indocyanine green , showing an improvement in effective liver perfusion and function . No significant changes in HVPG and liver function were observed in patients receiving placebo . The number of patients with adverse events did not differ significantly between groups . No patient was withdrawn from the study based on adverse events . CONCLUSIONS Simvastatin decreased HVPG and improved liver perfusion in patients with cirrhosis . These effects were additive with those of beta-adrenergic blockers . The beneficial effects of simvastatin should be confirmed in long-term clinical trials for portal hypertension BACKGROUND Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension . AIM We evaluated the effects of simvastatin on hepatic venous pressure gradient ( HVPG ) and azygos vein blood flow in cirrhotic patients . METHODS A 3-month prospect i ve , r and omized , triple-blind trial with simvastatin ( 40 mg/day ) vs. placebo was conducted in patients with cirrhotic portal hypertension . HVPG and azygos blood flow , measured by colour Doppler endoscopic ultrasound , were assessed before and after treatment . The primary endpoint was a decrease in the HVPG of at least 20 % from baseline or to ≤12 mmHg after the treatment . RESULTS 34 patients were prospect ively enrolled , and 24 completed the protocol . In the simvastatin group 6/11 patients ( 55 % ) presented a clinical ly relevant decrease in the HVPG ; no decrease was observed in the placebo group ( p=0.036 ) . Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin . HVPG and azygos blood flow values were not correlated . No significant adverse events occurred . CONCLUSION Simvastatin lowers portal pressure and may even improve liver function . The haemodynamic effect appears to be more evident in patients with severe portal hypertension |
12,186 | 12,076,411 | There was a small beneficial effect on both bulbar and limb function , but not on muscle strength .
REVIEW ER 'S CONCLUSIONS Riluzole 100 mg daily is reasonably safe and probably prolongs survival by about two months in patients with amyotrophic lateral sclerosis . | BACKGROUND Riluzole has been approved for treatment of patients with amyotrophic lateral sclerosis in many countries but not all .
Questions persist about its clinical utility because of high cost , modest efficacy and concern over adverse effects .
OBJECTIVES To examine the efficacy of riluzole in prolonging survival , and in delaying the use of surrogates ( tracheostomy and mechanical ventilation ) to sustain survival . | We performed a 3-month , double-blind , placebo-controlled trial of 300 mg of gangliosides ( Cronassial ) in 40 out patients with amyotrophic lateral sclerosis ( ALS ) . We evaluated drug effect through physical examinations and symptom scales . Though this dosage had no major toxic effect , Cronassial treatment did not significantly benefit ALS patients Two double-blinded , placebo-controlled clinical trials of riluzole have now been carried out in more than 1,100 patients with ALS . The results of both studies show a modest benefit in prolonging survival that is statistically significant . These results led to the availability of this drug by the Food and Drug Administration for use in the United States beginning in early 1996 . This is the first drug that has been available for ALS . It begins a new era in both basic and clinical research in an attempt to find a cure for this disease . NEUROLOGY 1996;47(Suppl 2 ) : BACKGROUND In an attempt to better underst and and define the progression of amyotrophic lateral sclerosis ( ALS ) , we developed a classification of 5 discrete health states that reflect patients ' activities of daily living . These health states were used to determine whether patients with ALS who are treated with riluzole differed from those treated with placebo . SETTING Clinics for patients with ALS . DESIGN Placebo-controlled trial of riluzole treatment in 959 patients with ALS . INTERVENTIONS Treatment with riluzole or placebo . MAIN DEPENDENT MEASURES : A Cox model was used to assess whether , from the initial r and omization to the end of an 18-month follow-up , there was a difference in the times of transition into subsequent health states between patients treated with riluzole and those treated with placebo . RESULTS Our analysis showed a significant difference in the time to transit between the riluzole and the placebo groups in less severely affected cases , ie , state 2 and state A ( the milder states ) of ALS . CONCLUSION Patients receiving riluzole remained in the milder health states longer ( P<.05 ) A population of 31 patients with sporadic amyotrophic lateral sclerosis ( ALS ) was selected for a prospect i ve open study based on treatment with riluzole . A neurophysiological evaluation was performed by means of single and paired transcranial magnetic stimulation ( TMS ) . The examined parameters , excitability threshold , motor evoked potential ( MEP ) duration , silent period ( SP ) duration and time course of intracortical inhibition to paired TMS after 6 months treatment , were matched against those recorded from the patients themselves before the beginning of treatment and from 20 ( single TMS ) or 10 ( paired TMS ) age-matched control subjects . Normal behaviour of the SP in response to increasing TMS was found in the treated patients ; they showed a significant linear correlation between these two parameters ( r=0.96 ) comparable to that calculated for controls ( r=0.98 ) , and significantly different with respect to drug-free patients ( r=0.8 , P=0.014 ) . A significant reduced size of the ' conditioned ' MEPs to paired stimulation was documented in the treated patients compared with the untreated patients ( P=0.002 ) . Our neurophysiological contribution to the assessment of the effect of riluzole on the motor cortical inhibitory property in ALS may be considered a setting for controlled trials in extended patient series , even in a pre- clinical phase RILUZOLE , a glutamate antagonist , has been shown to be efficacious in the treatment of patients with amyotrophic lateral sclerosis ( ALS ) , allowing prolonged survival and time to tracheostomy . The efficacy of riluzole in thought to result from reduced glutamate excitotoxicity on motor neurons of patients with ALS , but this has never been demonstrated directly in vivo . N-acetylaspartate ( NAA ) , a compound that is readily measured in vivo using proton magnetic resonance spectroscopy , can be used as a surrogate marker for neuronal loss or sublethal injury . To determine whether riluzole reverses sublethal corticomotoneuron damage in patients with ALS we measured NAA/creatine ( Cr ) relative intensity ratios in the motor cortex before and after treatment with riluzole 50 mg bid . After 3 weeks of riluzole therapy in 11 patients NAA/Cr increased from 2.14 ± 0.26 to 2.27 ± 0.24 ( p = 0.044 ) , whereas , in 12 untreated patients NAA/Cr decreased from 2.17 ± 0.20 to 2.08 ± 0.20 ( p = 0.099 ) . Thus the change in NAA/Cr between the treated and untreated groups was 0.22 ± 0.095 ( p = 0.008 ) . The magnitude of increase in NAA/Cr in those treated was not correlated with age , sex , duration of treatment or disease , the presence of probable or definite upper motor neuron ( UMN ) signs , bulbar features , or pre-treatment NAA/Cr . We conclude that magnetic resonance spectroscopy can provide a novel surrogate measure of neuronal integrity that demonstrates reversal of sublethal UMN injury in patients with ALS within weeks of initiating riluzole therapy |
12,187 | 26,426,785 | CONCLUSIONS Following the strategies delineated in this policy statement may help sites to develop comprehensive LDCT screening programs that are safe and effective | RATIONALE Annual low-radiation-dose computed tomography ( LDCT ) screening for lung cancer has been shown to reduce lung cancer mortality among high-risk individuals and is now recommended by multiple organizations .
However , LDCT screening is complex , and implementation requires careful planning to ensure benefits outweigh harms .
Little guidance has been provided for sites wishing to develop and implement lung cancer screening programs .
OBJECTIVES To promote successful implementation of comprehensive LDCT screening programs that are safe , effective , and sustainable . | BACKGROUND Lung cancer screening might be a teachable moment for smoking cessation intervention . The objective was to investigate whether a tailored self-help smoking cessation intervention is more effective in inducing smoking cessation compared to a st and ard brochure in male smokers who participate in the Dutch-Belgian r and omised controlled lung cancer screening trial ( NELSON trial ) . METHODS Two r and om sample s of male smokers who had received either a st and ard brochure ( n=642 ) or a tailoring question naire for computer-tailored smoking cessation information ( n=642 ) were sent a question naire to measure smoking behaviour two years after r and omisation . RESULTS Twenty-three percent of the male smokers in the tailored information group returned a completed tailoring question naire and thus received the tailored advice . The prolonged smoking abstinence was slightly , but not statistically significant , lower amongst those r and omised in the tailored information group ( 12.5 % ) compared with the brochure group ( 15.6 % ) ( OR=0.77 ( 95%-CI : 0.56 - 1.06 ) . The level of education and intention to quit smoking significantly predicted smoking cessation at follow-up ( p<0.05 ) . The majority of the respondents did not recall whether and which smoking cessation intervention they had received at r and omisation after 2-years of follow-up . CONCLUSION The current study showed no advantage of tailored smoking cessation information over st and ard self-help information amongst male smokers with a long term smoking history who participate in a lung cancer screening trial after two years of follow-up . However , the low percentage participants who actually received the tailored advice limited the ability to find an advantage 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 The National Lung Screening Trial ( NLST ) has sparked new interest in the adoption of lung cancer screening using low-dose computed tomography ( LDCT ) . If adopted at a national level , LDCT screening may prevent approximately 18,000 lung cancer deaths per year , potentially constituting a high-value public health intervention . Before incorporating LDCT screening into practice , health care institutions need to consider the risks associated with LDCT screening and the impact of LDCT screening on health care costs , as well as other remaining areas of uncertainty , including the unknown cost-effectiveness of LDCT screening . This article will review the benefits and risks of LDCT screening in light of the results of the NLST and other r and omized trials , it will discuss the additional health care costs associated with LDCT screening from the perspective of health care payers , and it will examine the published cost-effectiveness analyses of LDCT screening . A subsequent discussion highlights guideline recommendations for implementation strategies , the goals of which are to ensure that those eligible for LDCT screening derive the benefits while minimizing the risks of screening and avoiding an unnecessary escalation in screening-related costs . The article concludes by endorsing the use of LDCT screening in institutions capable of responsible implementation of screening in both medical and economic terms . The key elements of responsible implementation include the development of st and ardized screening practice s , careful selection of screening c and i date s , and the creation of prospect i ve registries that will mitigate current areas of uncertainty regarding LDCT screening BACKGROUND Reliable risk prediction tools for estimating individual probability of lung cancer have important public health implication s. We constructed and vali date d a comprehensive clinical tool for lung cancer risk prediction by smoking status . METHODS Epidemiologic data from 1851 lung cancer patients and 2001 matched control subjects were r and omly divided into separate training ( 75 % of the data ) and validation ( 25 % of the data ) sets for never , former , and current smokers , and multivariable models were constructed from the training sets . The discriminatory ability of the models was assessed in the validation sets by examining the areas under the receiver operating characteristic curves and with concordance statistics . Absolute 1-year risks of lung cancer were computed using national incidence and mortality data . An ordinal risk index was constructed for each smoking status category by summing the odds ratios from the multivariable regression analyses for each risk factor . RESULTS All variables that had a statistically significant association with lung cancer ( environmental tobacco smoke , family history of cancer , dust exposure , prior respiratory disease , and smoking history variables ) have strong biologically plausible etiologic roles in the disease . The concordance statistics in the validation sets for the never , former , and current smoker models were 0.57 , 0.63 , and 0.58 , respectively . The computed 1-year absolute risk of lung cancer for a hypothetical male current smoker with an estimated relative risk close to 9 was 8.68 % . The ordinal risk index performed well in that true-positive rates in the design ated high-risk categories were 69 % and 70 % for current and former smokers , respectively . CONCLUSIONS If confirmed in other studies , this risk assessment procedure could use easily obtained clinical information to identify individuals who may benefit from increased screening surveillance for lung cancer . Although the concordance statistics were modest , they are consistent with those from other risk prediction models Objective To evaluate the impact of telling patients their estimated spirometric lung age as an incentive to quit smoking . Design R and omised controlled trial . Setting Five general practice s in Hertfordshire , Engl and . Participants 561 current smokers aged over 35 . Intervention All participants were offered spirometric assessment of lung function . Participants in intervention group received their results in terms of “ lung age ” ( the age of the average healthy individual who would perform similar to them on spirometry ) . Those in the control group received a raw figure for forced expiratory volume at one second ( FEV1 ) . Both groups were advised to quit and offered referral to local NHS smoking cessation services . Main outcome measures The primary outcome measure was verified cessation of smoking by salivary cotinine testing 12 months after recruitment . Secondary outcomes were reported changes in daily consumption of cigarettes and identification of new diagnoses of chronic obstructive lung disease . Results Follow-up was 89 % . Independently verified quit rates at 12 months in the intervention and control groups , respectively , were 13.6 % and 6.4 % ( difference 7.2 % , P=0.005 , 95 % confidence interval 2.2 % to 12.1 % ; number needed to treat 14 ) . People with worse spirometric lung age were no more likely to have quit than those with normal lung age in either group . Cost per successful quitter was estimated at £ 280 ( € 366 , $ 556 ) . A new diagnosis of obstructive lung disease was made in 17 % in the intervention group and 14 % in the control group ; a total of 16 % ( 89/561 ) of participants . Conclusion Telling smokers their lung age significantly improves the likelihood of them quitting smoking , but the mechanism by which this intervention achieves its effect is unclear . Trial registration National Research Register N0096173751 BACKGROUND Although there is no proven benefit associated with screening for lung cancer , screening programs are attracting many individuals who perceive themselves to be at high risk due to smoking . We sought to determine whether the risk of lung cancer varies predictably among smokers . METHODS We used data on 18 172 subjects enrolled in the Carotene and Retinol Efficacy Trial (CARET)-a large , r and omized trial of lung cancer prevention-to derive a lung cancer risk prediction model . Model inputs included the subject 's age , sex , asbestos exposure history , and smoking history . We assessed the model 's calibration by comparing predicted and observed rates of lung cancer across risk deciles and vali date d it by assessing the extent to which a model estimated on data from five CARET study sites could predict events in the sixth study site . We then applied the model to evaluate the risk of lung cancer among smokers enrolled in a study of lung cancer screening with computed tomography ( CT ) . RESULTS The model was internally valid and well calibrated . Ten-year lung cancer risk varied greatly among participants in the CT study , from 15 % for a 68-year-old man who has smoked two packs per day for 50 years and continues to smoke , to 0.8 % for a 51-year-old woman who smoked one pack per day for 28 years before quitting 9 years earlier . Even among the subset of CT study participants who would be eligible for a clinical trial of cancer prevention , risk varied greatly . CONCLUSIONS The risk of lung cancer varies widely among smokers . Accurate risk prediction may help individuals who are contemplating voluntary screening to balance the potential benefits and risks . Risk prediction may also be useful for research ers design ing clinical trials of lung cancer prevention STUDY OBJECTIVES To develop and vali date a model for estimating the risk of lung cancer death in current and former smokers . The model is intended for use in analyzing a population of subjects who are undergoing lung cancer screening or receiving lung cancer chemoprevention , to determine whether the intervention has altered lung cancer mortality . DESIGN / SETTING / PATIENTS Model derivation was based on analyses of the placebo arm of the Carotene and Retinol Efficacy Trial . Model validation was based on analyses of three other longitudinal cohorts . MEASUREMENTS Observed and predicted number of deaths due to lung cancer . RESULTS In internal validation , the model was highly concordant and well calibrated . In external validation , the model predictions were similar to what was observed in all of the validation analyses . The predicted and observed deaths within 6 years were very similar when assessed in the Johns Hopkins Hospital trial of chest radiography and sputum cytology screening ( 176 predicted , 184 observed , p = 0.53 ) , the Memorial Sloan-Kettering Cancer Center trial of chest radiography and sputum cytology screening ( 108 predicted , 114 observed , p = 0.57 ) , and the National Health and Nutrition Evaluation Survey part I ( 24 predicted , 21 observed , p = 0.52 ) . CONCLUSIONS The number of lung cancer deaths in a population of current or former smokers can be accurately predicted , making model-based evaluations of prevention and early detection interventions a useful adjunct to definitive r and omized trials . We illustrate this potential use with a small example Editors ' Notes Context The definitions used to classify low-dose computed tomography findings may markedly influence the benefits and harms of lung cancer screening . Contribution This analysis of data from a large screening trial found that using the recently proposed Lung-RADS approach to classifying low-dose computed tomography findings substantially decreased the false-positive result rate but with a concomitant decrease in sensitivity . Implication Adopting the Lung-RADS classification system may improve the results of lung cancer screening programs . The U.S. Preventive Services Task Force recently recommended ( grade B ) lung cancer screening with low-dose computed tomography ( LDCT ) for high-risk current and former smokers ( 1 ) . The primary evidence used by the Task Force was the National Lung Screening Trial ( NLST ) , which reported a 20 % reduction in lung cancerspecific death associated with LDCT screening ( 2 ) . Important considerations for widespread use of LDCT lung cancer screening in clinical practice include the definition of a positive result in computed tomography ( CT ) screening and the appropriate management of positive screening results . Much knowledge has accumulated since the NLST was design ed in 2002 . In this trial , the definition of a positive screening result was a nodule of 4 mm or greater in the longest diameter that had no specific benign calcification patterns . In addition , the NLST achieved its results without a trial-wide specified protocol for diagnostic management for positive screening results . A recent re analysis of the NLST examined the effect of different cutoffs defining a positive screening result and found that increasing the threshold to 6 or 8 mm would have result ed in substantial decreases in the false-positive result rate with only small corresponding decreases in sensitivity ( 3 ) . The International Early Lung Cancer Action Program reported similar results for baseline LDCT screenings , showing a substantial reduction in the positivity rate of screening results with increasing size cutoffs and only a few result ant missed cancer cases ( 4 ) . Over this period , several professional organizations have promulgated lung cancer screening guidelines , many of which define a positive screening result and include nodule management ( 57 ) . The American College of Radiology recently began efforts to st and ardize the reporting of LDCT screening results in a manner analogous to the use of the Breast Imaging Reporting and Data System for mammography , based on the best available data . This effort included defining a positive result on lung cancer screening CT in the most effective manner , attempting to reduce the substantial false-positive result rate while having the least possible effect on test sensitivity , and suggesting management recommendations based on lung cancer risk . Published data from several LDCT screening studies , including the NLST , the International Early Lung Cancer Action Program , and the European NELSON ( Nederl and s-Leuvens Longkanker Screenings Onderzoek ) trial , were used by a consensus panel to help derive positivity criteria for Lung-RADS ( 4 , 810 ) , which was officially released in May 2014 ( 11 ) . Compared with the NLST criteria , Lung-RADS increases the size threshold for a positive baseline screening result from a 4-mm greatest transverse diameter to a 6-mm transverse bidimensional average ( and to 20 mm for nonsolid nodules ) and requires growth for preexisting nodules . Although data from the NLST , in part , were used to develop the Lung-RADS criteria , only published summary -level data were considered . These data were sufficient to give an approximate positivity rate for Lung-RADS as applied to the NLST but not to give an exact distribution of Lung-RADS scores . This is especially the case for screenings after baseline , where the individual nodule history over time is critical in defining the Lung-RADS category . We used participant- and nodule-level data to retrospectively apply the Lung-RADS criteria to the NLST . We evaluate the effect of Lung-RADS on the performance characteristics of LDCT screening , including sensitivity , false-positive result rate , positive predictive value ( PPV ) , and negative predictive value ( NPV ) . In addition , we compare the characteristics of the cancer cases detectable by Lung-RADS with those that it would have missed . Methods NLST Design The NLST r and omly assigned participants aged 55 to 74 years to LDCT or chest radiography screening . Eligibility criteria included 30 pack-years of smoking or greater and current smoking status or having quit within the past 15 years ( 12 ) . Participants were recruited at 33 U.S. centers from 2002 to 2004 and received either LDCT or chest radiography over 3 annual screening rounds ( denoted T0 , T1 , and T2 ) . The NLST was approved by the institutional review board at each screening center , and all participants provided informed consent . The NLST study protocol defined a noncalcified nodule ( NCN ) of 4 mm or greater in the longest transverse diameter as a positive screening result . For each NCN that was 4 mm or greater , radiologists used st and ardized forms to report location , greatest transverse and perpendicular diameters , margins , and attenuation characteristics . At T1 and T2 , they reported whether the abnormality was preexisting or new based on examinations of previous images and , if preexisting , whether it had grown and whether a suspicious change in attenuation had occurred since past screenings . Noncalcified nodules that were unchanged from T0 to T2 , representing stability for 2 years , could be considered benign and constitute a negative screening result at the radiologist 's discretion . Other abnormalities , including adenopathy or effusion , could also trigger positive screening results . Positive results were tracked for result ant diagnostic procedures and lung cancer diagnoses . In addition , participants were followed with annual surveys to ascertain incident cancer cases . All reported cancer cases were verified with medical records , with stage and histologic characteristics recorded . Deaths were tracked with the annual surveys and supplemented by National Death Index search es . Lung-RADS Table 1 describes the primary criteria for defining Lung-RADS categories . Categories 1 ( negative ) and 2 ( benign appearance ) correspond to negative screening results , and categories 3 ( probably benign ) and 4 ( suspicious ) correspond to positive screening results . Category 4 is further divided into 4A , 4B , and 4X ( 8) . In the context of annual screening , a negative screening result assumes that reevaluation will occur at the next annual screening , whereas a positive screening result means that additional evaluation is recommended before the next annual screening . The distinctions between the positive screening categories are important because Lung-RADS management guidelines differ substantially across categories , ranging from follow-up CT at 6 months for category 3 to positron emission tomography and CT or biopsy for 4B . In addition , category 2 involves tracking small nodules on the next annual screening , and category 1 does not involve tracking nodules . Table 1 . Summary of Lung-RADS Classification Lung-RADS criteria distinguish between baseline ( first ) and subsequent screenings . For baseline screenings ( generally lacking comparison examinations ) , the criteria are based on nodule size , as measured by average diameter , and nodule attenuation ( solid , part-solid , or nonsolid ) . For subsequent screenings , the criteria also consider the preexistence and growth of the nodule . For baseline screenings , positive screening results for solid and part-solid nodules require a size of 6 mm , and 20 mm is required for nonsolid ( that is , ground-glass ) nodules . For positivity on subsequent screenings , 4 mm is required for new ( solid or part-solid ) nodules , and preexisting nodules must show growth , defined as an increase in size of greater than 1.5 mm . New or growing nonsolid nodules still must meet the 20-mm size requirement . For part-solid nodules , the size and /or growth of the solid component is also considered . The overall Lung-RADS screening category is determined by the nodule with the highest individual Lung-RADS score . Category 3 or 4 nodules with additional features ( such as spiculation ) or imaging findings that increase suspicion for cancer ( such as enlarged lymph nodes ) can qualify as category 4X . Applying Lung-RADS to the NLST The average diameter for NLST nodules was computed as the mean of the longest diameter and the longest perpendicular diameter . The NLST attenuation classifications of soft tissue , ground glass , and mixed were mapped to the Lung-RADS classifications of solid , nonsolid , and part-solid , respectively . The NLST did not report the amount of growth but only whether growth occurred ; therefore , report of growth in the NLST was considered nodule growth for Lung-RADS . For part-solid nodules , the NLST did not report the size of the solid component , which may be required to distinguish among categories 3 , 4A , and 4B . Therefore , if NLST data for a part-solid nodule were consistent with 2 or more categories of 3 or higher , a range ( such as 3 to 4B ) instead of a single category was denoted for our analysis . These category ranges for part-solid nodules were used only if they constituted ( at the upper limit of their range ) the nodule with the highest degree of suspicion . In addition , the solid component was assumed to be growing if the nodule as a whole was reported as growing or there was a suspicious change in attenuation ; growth specifically of the solid component was not recorded in the NLST . If other suspicious findings , in the absence of any nodules measuring 4 mm or greater , constituted a positive screening result in the NLST , this was classified as category 4X for Lung-RADS . Quantitative Methods Lung cancer was deemed to be present at a screening if it was diagnosed within 1 year or before the next screening ( whichever came first ) or , for Lung cancer screening with computed tomography has demonstrated a significant reduction in mortality . While these findings are important for the lung cancer research field , the most important risk factor for lung cancer , i.e. smoking , should not be ignored . We performed a pilot study to examine the feasibility of delivering a program that included both tobacco dependence treatment and lung cancer screening . The objectives of this study were to : ( 1 ) estimate the proportion of smokers who complied with a 12-week treatment protocol that included both tobacco dependence treatment and lung cancer screening , ( 2 ) obtain preliminary estimates of abstinence and quit attempts at 4 and 6 months , and ( 3 ) obtain preliminary estimates of the cognitive social health information processing ( C-SHIP ) constructs and how they change following the intervention . In this r and omized pilot study , 18 volunteers completed a 12-week protocol : half received the tobacco dependence treatment program before a CT scan ( BCT ) and the other received the CT scan first , followed by the treatment program ( ACT ) . The treatment protocol included both nurse-delivered telephone counseling and either nicotine replacement therapy or varenicline . Only one person did not complete all follow-up evaluations . At 4 months post enrollment , the carbon monoxide confirmed quit rates were 33.3 % in the BCT arm and 22.2 % in the ACT arm ( 27.8 % overall ) , and all but one had made a 24-h attempt to quit . At 6 months the confirmed abstinence decreased to 22.1 % in the BCT arm and 11.1 % in the ACT arm ( 16.7 % overall ) , and 72.2 % of participants had made a 24-h quit attempt . These preliminary results suggest that it might be better to deliver treatment before the screening test . Future r and omized trials with a larger sample size are needed to confirm these findings RATIONALE Incidental pulmonary nodule detection is postulated to cause distress , but the frequency and magnitude of that distress have not been reported . The quality of patient-clinician communication and the perceived risk of lung cancer may influence distress Objectives : To evaluate the association of communication processes with distress and the perceived risk of lung cancer using vali date d instruments . METHODS We conducted a prospect i ve cohort study of patients with incidentally detected nodules who received care at one Department of Veterans Affairs Medical Center . We measured distress with the Impact of Event Scale and patient-centered communication with the Consultation Care Measure , both vali date d instruments . Risk of lung cancer was self-reported by participants . We used multivariable adjusted logistic regression to measure the association of communication quality with distress . MEASUREMENTS AND MAIN RESULTS Among 122 Veterans with incidental nodules , 23 % , 12 % , and 4 % reported experiencing mild , moderate , and severe distress , respectively , at the time they were informed of the pulmonary nodule . Participant-reported risk of lung cancer was not associated with distress . In the adjusted model , high- quality communication was associated with decreased distress ( odds ratio [ OR ] = 0.28 , 95 % confidence interval [ CI ] = 0.08 - 1.00 , P = 0.05 ) . Among participants who reported a risk of malignancy of 30 % or less , high- quality communication was associated with decreased distress ( OR = 0.15 , 95 % CI = 0.02 - 0.92 , P = 0.04 ) , but was not associated with distress for those who reported a risk greater than 30 % ( OR = 0.12 ( 95 % CI = 0.00 - 3.97 , P = 0.24 ) , although the P value for interaction was not significant . CONCLUSIONS Veterans with incidental pulmonary nodules frequently reported inadequate information exchange regarding their nodule . Many patients experience distress after they are informed that they have a pulmonary nodule , and high- quality patient-clinician communication is associated with decreased distress . Communication strategies that only target improved knowledge of the risk of malignancy may not be sufficient to reduce the distress associated with nodule detection R and omized controlled trials of smoking interventions have not been well-documented for lung cancer screening population s. In this study , we r and omly assigned 171 current smokers who were undergoing low-dose fast spiral chest CT ( SCTS ) for lung cancer screening to receive either st and ard written self-help material s or a written list of Internet re sources for smoking cessation . At the 1-year follow-up , more of the subjects receiving Internet-based re sources reported making a stop attempt ( 68 % versus 48 % , P=0.011 ) . However , there were no statistically significant differences in 7-day point prevalence quit rates ( 5 % versus 10 % ) or advancement in motivational readiness to stop smoking ( 27 % versus 30 % ) , respectively , between the groups . Clearly , more investigation is warranted into how to tailor smoking interventions for cancer screening participants BACKGROUND The main challenge in CT screening for lung cancer is the high prevalence of pulmonary nodules and the relatively low incidence of lung cancer . Management protocol s use thresholds for nodule size and growth rate to determine which nodules require additional diagnostic procedures , but these should be based on individuals ' probabilities of developing lung cancer . In this prespecified analysis , using data from the NELSON CT screening trial , we aim ed to quantify how nodule diameter , volume , and volume doubling time affect the probability of developing lung cancer within 2 years of a CT scan , and to propose and evaluate thresholds for management protocol s. METHODS Eligible participants in the NELSON trial were those aged 50 - 75 years , who have smoked 15 cigarettes or more per day for more than 25 years , or ten cigarettes or more for more than 30 years and were still smoking , or had stopped smoking less than 10 years ago . Participants were r and omly assigned to low-dose CT screening at increasing intervals , or no screening . We included all participants assigned to the screening group who had attended at least one round of screening , and whose results were available from the national cancer registry data base . We calculated lung cancer probabilities , stratified by nodule diameter , volume , and volume doubling time and did logistic regression analysis using diameter , volume , volume doubling time , and multinodularity as potential predictor variables . We assessed management strategies based on nodule threshold characteristics for specificity and sensitivity , and compared them to the American College of Chest Physicians ( ACCP ) guidelines . The NELSON trial is registered at www.trialregister.nl , number IS RCT N63545820 . FINDINGS Volume , volume doubling time , and volumetry-based diameter of 9681 non-calcified nodules detected by CT screening in 7155 participants in the screening group of NELSON were used to quantify lung cancer probability . Lung cancer probability was low in participants with a nodule volume of 100 mm(3 ) or smaller ( 0·6 % [ 95 % CI 0·4 - 0·8 ] ) or maximum transverse diameter smaller than 5 mm ( 0·4 % [ 0·2 - 0·7 ] ) , and not significantly different from participants without nodules ( 0·4 % [ 0·3 - 0·6 ] , p=0·17 and p=1·00 , respectively ) . Lung cancer probability was intermediate ( requiring follow-up CT ) if nodules had a volume of 100 - 300 mm(3 ) ( 2·4 % [ 95 % CI 1·7 - 3·5 ] ) or a diameter 5 - 10 mm ( 1·3 % [ 1·0 - 1·8 ] ) . Volume doubling time further stratified the probabilities : 0·8 % ( 95 % CI 0·4 - 1·7 ) for volume doubling times 600 days or more , 4·0 % ( 1·8 - 8·3 ) for volume doubling times 400 - 600 days , and 9·9 % ( 6·9 - 14·1 ) for volume doubling times of 400 days or fewer . Lung cancer probability was high for participants with nodule volumes 300 mm(3 ) or bigger ( 16·9 % [ 95 % CI 14·1 - 20·0 ] ) or diameters 10 mm or bigger ( 15·2 % [ 12·7 - 18·1 ] ) . The simulated ACCP management protocol yielded a sensitivity and specificity of 90·9 % ( 95 % CI 81·2 - 96·1 ) , and 87·2 % ( 86·4 - 87·9 ) , respectively . A diameter-based protocol with volumetry-based nodule diameter yielded a higher sensitivity ( 92·4 % [ 95 % CI 83·1 - 97·1 ] ) , and a higher specificity ( 90·0 % [ 89·3 - 90·7 ) . A volume-based protocol ( with thresholds based on lung cancer probability ) yielded the same sensitivity as the ACCP protocol ( 90·9 % [ 95 % CI 81·2 - 96·1 ] ) , and a higher specificity ( 94·9 % [ 94·4 - 95·4 ] ) . INTERPRETATION Small nodules ( those with a volume < 100 mm(3 ) or diameter < 5 mm ) are not predictive for lung cancer . Immediate diagnostic evaluation is necessary for large nodules ( ≥300 mm(3 ) or ≥10 mm ) . Volume doubling time assessment is advocated only for intermediate-sized nodules ( with a volume ranging between 100 - 300 mm(3 ) or diameter of 5 - 10 mm ) . Nodule management protocol s based on these thresholds performed better than the simulated ACCP nodule protocol . FUNDING Zorgonderzoek Nederl and Medische Wetenschappen and Koningin Wilhelmina Fonds BACKGROUND Lung cancer screening may serve as a ' teachable moment ' for smoking cessation , a brief period in which motivation to stop smoking is enhanced . Within the context of two NCI-funded r and omized lung screening trials , we conducted an ancillary study to explore the impact of screening on smoking cessation and readiness to stop smoking . METHODS We accrued a sample of current and former smokers participating at the Georgetown University site of the Lung Screening Study ( LSS ; N=144 ) and of the National Lung Screening Trial ( NLST ; N=169 ) . In each sample , we assessed reasons for trial participation , interest in smoking cessation interventions , motivations for stopping smoking , and the impact of undergoing screening on tobacco use and readiness to stop smoking . Telephone interviews were conducted prior to screening , and 1-month following receipt of the screening result . The sample s were analyzed separately due to differences in age and level of nicotine dependence . RESULTS The majority of the findings were consistent across the two sample s. Frequently endorsed reasons for trial participation among both current and former smokers included psychological reasons ( e.g. , wanting peace of mind about lung cancer ) and altruism ( e.g. , wanting to make a contribution to science ) . Nicotine replacement therapy and free counseling were the cessation methods that were of most interest , and fear of lung health problems was the most frequently endorsed motivation for quitting smoking . Regarding readiness to stop smoking , approximately 20 % were ready to stop in the next 30 days , 45 % were ready to stop in the next 6 months , while 35 % were not thinking of stopping . At the follow-up , 7 % of current smokers at baseline reported abstinence , and 4 % of former smokers at baseline reported having relapsed . The findings differed across the two sample s when considering the readiness to quit outcome . At the 1-month follow-up of the NLST sample , participants became more ready to stop smoking ( p<.05 ) . Screening result did not moderate this finding . In the LSS sample , among younger participants ( < or=64 ) , an abnormal screening result was significantly associated with becoming more ready to stop smoking , whereas a normal result was associated with becoming less ready to stop smoking ( p=.02 ) . CONCLUSIONS The current findings demonstrated the feasibility of enrolling lung screening participants into a smoking-related research study , as well as the high level of interest in stopping smoking and in smoking cessation interventions . These data indicate that lung cancer screening may serve as a teachable moment for smoking cessation , and suggest that a smoking cessation trial within the context of lung cancer screening is feasible Last winter , the U.S. Preventive Services Task Force ( USPSTF ) gave a positive recommendation ( B grade ) for lung cancer screening with low-dose computed tomography . The recommendation applies to high-risk adults aged 55 to 80 years with a smoking history of at least 30 pack-years who are still smoking or have quit within the past 15 years ( 1 ) . The USPSTF based its recommendation on the l and mark National Lung Screening Trial ( NLST ) ( 2 ) , which provided evidence about the efficacy of screening but did not answer questions about effectiveness when implemented in everyday clinical practice . The recommendation , as noted in an accompanying editorial , leaves many of these critical issues unaddressed ( 3 ) . Indeed , the Medicare Evidence Development & Coverage Advisory Committee recently concluded that there was inadequate evidence to recommend national coverage for lung cancer screening ( 4 ) . This conclusion highlights the controversy over what constitutes sufficient evidence to support widespread implementation of a new technology . It has also heightened the tension between advocates who are eager to see wide deployment of screening quickly and others who are concerned about the ability of health care systems to provide a low-dose computed tomography screening program to the potentially large number of patients meeting criteria while still minimizing harms ( 4 ) . That a new intervention can work in r and omized trials does not guarantee that it will work as well when delivered in real-world practice , nor that the benefits in the community will justify the possible harms and costs ( including opportunity costs ) . Should these unanswered questions delay implementation of screening pending further study , or do the potential benefits compel their early adoption ? A middle-ground approach between early adoption and waiting years for more conclusive evidence is to carefully plan and evaluate a comprehensive approach to lung cancer screening , including a staged and limited implementation and evaluation program before broader implementation . The Veterans Health Administration ( VHA ) , the nation 's largest integrated health care system , has chosen this approach by developing a 2-year clinical demonstration project involving 8 VHA medical centers that serve more than 500000 veterans . This decision is based on some of the uncertainties , as outlined by the Medicare Evidence Development & Coverage Advisory Committee , as well as questions about the effect of screening on our patients , our staff , and our system . At the same time , the compelling results of NLST and high burden of smoking and lung cancer among veterans argue against a wait- and -see approach . Before committing to widespread screening , we want to determine the following : Can we effectively identify the right c and i date s to offer screening in the course of routine care ? What will the uptake of screening be and what re sources ( both technology and people ) are needed to meet that dem and ? Can we provide screening and follow-up ( including for the many patients with benign nodules ) with accuracy , efficiency , and safety similar to that achieved in the NLST ? Are the overall outcomes in our patients with early-stage cancer ( especially those who are older with more comorbid conditions ) compatible with a benefit of early detection ? To ensure that all veterans benefit , and not just those who request them , the VHA takes a proactive approach to all preventive programs . It is critically important to learn how to do this efficiently and effectively . At demonstration sites , annual screening will be provided , as recommended by the USPSTF . Full-time coordinators hired for the project will provide clinical coordination for patients who choose to be screened , using newly developed tracking tools and data bases . Structure , process , and outcome measures have been developed using quantitative and qualitative data from clinical data in electronic medical records , regular reports from pilot sites , quality assessment s of radiology reports , surveys and interviews of key clinical staff , and cost estimates for the screening program ( 5 ) . Clinical data include demographic characteristics , smoking history , and health status of those screened ; descriptions of identified nodules ; numbers and types of scans and other procedures performed initially and to evaluate abnormal findings ; adverse events from invasive procedures ; numbers and types of incidental findings and their follow-up ; and lung cancer cases diagnosed . These data will help assess whether the predominantly older , male VHA population with several chronic conditions has different outcomes with screening from those of the younger , healthier NLST population . At its conclusion , the project team will make recommendations about the processes and re sources needed for wider VHA dissemination of a lung cancer screening program and , if deemed feasible , appropriate metrics to monitor the process going forward . This quality improvement project , which is design ed to assess implementation , will not be able to determine the effect of screening on mortality rates . However , it will help determine whether the VHA can provide high- quality screening while minimizing possible harms , whether outcomes vary by site or patient group , and what re sources would be needed for national implementation . The VHA faces challenges in taking the time to implement screening in a limited way . Public interest in lung cancer screening has helped prompt individual screening programs at many VHA medical centers outside the demonstration project , potentially creating inconsistencies across the organization . Even if the demonstration project is successful , VHA-wide implementation of lung cancer screening will be challenging for a system of 151 medical centers of varying size and capacity , and it will require new processes to monitor quality , ensure adequate capacity , and track outcomes . The complexity of such a program can not be underestimated . In addition , we will need to be careful that a focus on implementation of a screening program does not detract attention from a far more effective means of reducing lung cancer deaths : smoking cessation interventions . The VHA 's experience with implementation of a lung cancer screening program may provide valuable lessons learned for other large health care organizations . This extends beyond the screening registries required by many proponents of screening ( 6 , 7 ) to the development of tools for patient identification , data collection , quality assessment , and patient education . The VHA 's population and its payment structure may limit the generalizability of our experience , but we believe that documenting the VHA 's demonstration project 's challenges , successes , and failures may help the U.S. health care system decrease the morbidity and mortality rates due to lung cancer in a way that provides the best balance between benefits and harms 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 PURPOSE To measure reader agreement in determining whether lung nodules detected at baseline screening computed tomography ( CT ) had changed at subsequent screening examinations and to evaluate the variability in recommendations for further follow-up . MATERIAL S AND METHODS All subjects were enrolled in the National Lung Screening Trial ( NLST ) , and each participant consented to the use of their de-identified images for research purpose s. The authors r and omly selected 100 cases of nodules measuring at least 4.0 mm at 1-year screening CT that were considered by the original screening CT reader to be present on baseline CT scans ; nodules considered by the original reader to have changed were over sample d. Selected images from each case showing the entire nodule at both examinations were preloaded on a picture archiving and communication system workstation . Nine radiologists served as readers , and they evaluated whether the nodule was present at baseline and recorded the bidimensional measurements and nodule characteristics at each examination , presence or absence of change , results of screening CT , and follow-up recommendations ( high-level follow-up , low-level follow-up , no follow-up ) . RESULTS On the basis of review s during case selection , five nodules seen at follow-up were judged not to have been present at baseline ; for 19 of the remaining 95 cases , at least one reader judged the nodule not to have been present at baseline . For the 76 nodules that were unanimously considered to have been present at baseline , 21%-47 % ( mean ± st and ard deviation , 30 % ± 9 ) were judged to have grown . The κ values were similar for growth ( κ = 0.55 ) and a positive screening result ( κ = 0.51 ) and were lower for a change in margins and attenuation ( κ = 0.27 - 0.31 ) . The κ value in the recommendation of high- versus low-level follow-up was high ( κ = 0.66 ) . CONCLUSION Reader agreement on nodule growth and screening result was moderate to substantial . Agreement on follow-up recommendations was lower |
12,188 | 30,062,609 | The qualitative synthesis revealed a treatment advantage of combined therapy with nab-paclitaxel , while the meta- analysis on anti-VEGF/VEGFR drugs demonstrated marginal improvement of objective response rates and progression-free survival , but not overall survival . | Abundant tumor stroma is a hallmark of pancreatic ductal adenocarcinoma ( PDAC ) , and is suggested to play a role in the resistance of this deadly disease to systemic treatment .
Despite promising results from pre clinical studies , clinical trials with therapies targeting the tumor stroma and the vascular endothelial growth factor ( VEGF ) and its receptor VEGFR yielded conflicting results .
With this systematic review and meta- analysis , we aim to summarize the existing evidence in this important field with a special focus on anti-VEGF/VEGFR therapy . | Background Anti-angiogenic treatment is believed to have at least cystostatic effects in highly vascularized tumours like pancreatic cancer . In this study , the treatment effects of the angiogenesis inhibitor Cilengitide and gemcitabine were compared with gemcitabine alone in patients with advanced unresectable pancreatic cancer . Methods A multi-national , open-label , controlled , r and omized , parallel-group , phase II pilot study was conducted in 20 centers in 7 countries . Cilengitide was administered at 600 mg/m2 twice weekly for 4 weeks per cycle and gemcitabine at 1000 mg/m2 for 3 weeks followed by a week of rest per cycle . The planned treatment period was 6 four-week cycles . The primary endpoint of the study was overall survival and the secondary endpoints were progression-free survival ( PFS ) , response rate , quality of life ( QoL ) , effects on biological markers of disease ( CA 19.9 ) and angiogenesis ( vascular endothelial growth factor and basic fibroblast growth factor ) , and safety . An ancillary study investigated the pharmacokinetics of both drugs in a subset of patients . Results Eighty-nine patients were r and omized . The median overall survival was 6.7 months for Cilengitide and gemcitabine and 7.7 months for gemcitabine alone . The median PFS times were 3.6 months and 3.8 months , respectively . The overall response rates were 17 % and 14 % , and the tumor growth control rates were 54 % and 56 % , respectively . Changes in the levels of CA 19.9 went in line with the clinical course of the disease , but no apparent relationships were seen with the biological markers of angiogenesis . QoL and safety evaluations were comparable between treatment groups . Pharmacokinetic studies showed no influence of gemcitabine on the pharmacokinetic parameters of Cilengitide and vice versa . Conclusion There were no clinical ly important differences observed regarding efficacy , safety and QoL between the groups . The observations lay in the range of other clinical studies in this setting . The combination regimen was well tolerated with no adverse effects on the safety , tolerability and pharmacokinetics of either agent PURPOSE To define the safety , efficacy , and pharmacogenetic and pharmacodynamic effects of sorafenib with gemcitabine-based chemoradiotherapy ( CRT ) in locally advanced pancreatic cancer . METHODS AND MATERIAL S Patients received gemcitabine 1000 mg/m(2 ) intravenously weekly × 3 every 4 weeks per cycle for 1 cycle before CRT and continued for up to 4 cycles after CRT . Weekly gemcitabine 600 mg/m(2 ) intravenously was given during concurrent intensity modulated radiation therapy of 50 Gy to gross tumor volume in 25 fractions . Sorafenib was dosed orally 400 mg twice daily until progression , except during CRT when it was escalated from 200 mg to 400 mg daily , and 400 mg twice daily . The maximum tolerated dose cohort was exp and ed to 15 patients . Correlative studies included dynamic contrast-enhanced MRI and angiogenesis genes polymorphisms ( VEGF-A and VEGF-R2 single nucleotide polymorphisms ) . RESULTS Twenty-seven patients were enrolled . No dose-limiting toxicity occurred during induction gemcitabine/sorafenib followed by concurrent CRT . The most common grade 3/4 toxicities were fatigue , hematologic , and gastrointestinal . The maximum tolerated dose was sorafenib 400 mg twice daily . The median progression-free survival and overall survival for 25 evaluable patients were 10.6 and 12.6 months , respectively . The median overall survival for patients with VEGF-A -2578 AA , -1498 CC , and -1154 AA versus alternate genotypes was 21.6 versus 14.7 months . Dynamic contrast-enhanced MRI demonstrated higher baseline K(trans ) in responding patients . CONCLUSIONS Concurrent sorafenib with CRT had modest clinical activity with increased gastrointestinal toxicity in localized unresectable pancreatic cancer . Select VEGF-A/VEGF-R2 genotypes were associated with favorable survival Gemcitabine is a key drug for the treatment of pancreatic cancer ; however , with its limitation in clinical benefits , the development of another potent therapeutic is necessary . Vascular endothelial growth factor receptor 2 is an essential target for tumor angiogenesis , and we have conducted a phase I clinical trial using gemcitabine and vascular endothelial growth factor receptor 2 peptide ( elpamotide ) . Based on the promising results of this phase I trial , a multicenter , r and omized , placebo‐controlled , double‐blind phase II/III clinical trial has been carried out for pancreatic cancer . The eligibility criteria included locally advanced or metastatic pancreatic cancer . Patients were assigned to either the Active group ( elpamotide + gemcitabine ) or Placebo group ( placebo + gemcitabine ) in a 2:1 ratio by the dynamic allocation method . The primary endpoint was overall survival . The Harrington – Fleming test was applied to the statistical analysis in this study to evaluate the time‐lagged effect of immunotherapy appropriately . A total of 153 patients ( Active group , n = 100 ; Placebo group , n = 53 ) were included in the analysis . No statistically significant differences were found between the two groups in the prolongation of overall survival ( Harrington – Fleming P‐value , 0.918 ; log – rank P‐value , 0.897 ; hazard ratio , 0.87 , 95 % confidence interval [ CI ] , 0.486–1.557 ) . Median survival time was 8.36 months ( 95 % CI , 7.46–10.18 ) for the Active group and 8.54 months ( 95 % CI , 7.33–10.84 ) for the Placebo group . The toxicity observed in both groups was manageable . Combination therapy of elpamotide with gemcitabine was well tolerated . Despite the lack of benefit in overall survival , subgroup analysis suggested that the patients who experienced severe injection site reaction , such as ulceration and erosion , might have better survival Objectives In mouse models of pancreatic cancer , IPI-926 , an oral Hedgehog inhibitor , increases chemotherapy delivery by depleting tumor-associated stroma . This multicenter phase Ib study evaluated IPI-926 in combination with FOLFIRINOX ( 5-fluorouracil , leucovorin , irinotecan , oxaliplatin ) in patients with advanced pancreatic cancer . Methods Patients were treated with once-daily IPI-926 plus FOLFIRINOX . A 3 + 3 dose escalation design was used , with cohort expansion at the maximum tolerated dose . A subset of patients underwent perfusion computed tomography to assess changes in tumor perfusion . Results The maximum tolerated dose was identified 1 dose level below st and ard FOLFIRINOX . Common treatment-related adverse events included liver function test abnormalities , neuropathy , nausea/vomiting , and diarrhea . Objective response rate was high ( 67 % ) , and patients receiving IPI-926 maintenance showed further declines in CA19 - 9 levels even after FOLFIRINOX discontinuation . Treatment did not result in consistent increases in tumor perfusion . The study closed early when a separate phase II trial of IPI-926 plus gemcitabine indicated detrimental effects of this combination . Conclusions This is the first study to demonstrate the feasibility of using FOLFIRINOX as the chemotherapeutic backbone in a clinical trial design . Although robust antitumor activity and acceptable safety were observed with the addition of IPI-926 to this regimen , future development of Hedgehog inhibitors in pancreatic cancer seems unlikely BACKGROUND Nivolumab , a fully human IgG4 programmed death 1 ( PD-1 ) immune-checkpoint-inhibitor antibody , disrupts PD-1-mediated signaling and may restore antitumor immunity . METHODS In this r and omized , open-label , international phase 3 study , we assigned patients with nonsquamous non-small-cell lung cancer ( NSCLC ) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks . The primary end point was overall survival . RESULTS Overall survival was longer with nivolumab than with docetaxel . The median overall survival was 12.2 months ( 95 % confidence interval [ CI ] , 9.7 to 15.0 ) among 292 patients in the nivolumab group and 9.4 months ( 95 % CI , 8.1 to 10.7 ) among 290 patients in the docetaxel group ( hazard ratio for death , 0.73 ; 96 % CI , 0.59 to 0.89 ; P=0.002 ) . At 1 year , the overall survival rate was 51 % ( 95 % CI , 45 to 56 ) with nivolumab versus 39 % ( 95 % CI , 33 to 45 ) with docetaxel . With additional follow-up , the overall survival rate at 18 months was 39 % ( 95 % CI , 34 to 45 ) with nivolumab versus 23 % ( 95 % CI , 19 to 28 ) with docetaxel . The response rate was 19 % with nivolumab versus 12 % with docetaxel ( P=0.02 ) . Although progression-free survival did not favor nivolumab over docetaxel ( median , 2.3 months and 4.2 months , respectively ) , the rate of progression-free survival at 1 year was higher with nivolumab than with docetaxel ( 19 % and 8 % , respectively ) . Nivolumab was associated with even greater efficacy than docetaxel across all end points in subgroups defined according to prespecified levels of tumor-membrane expression ( ≥1 % , ≥5 % , and ≥10 % ) of the PD-1 lig and . Treatment-related adverse events of grade 3 or 4 were reported in 10 % of the patients in the nivolumab group , as compared with 54 % of those in the docetaxel group . CONCLUSIONS Among patients with advanced nonsquamous NSCLC that had progressed during or after platinum-based chemotherapy , overall survival was longer with nivolumab than with docetaxel . ( Funded by Bristol-Myers Squibb ; CheckMate 057 Clinical Trials.gov number , NCT01673867 . ) Inoperable cancer of the exocrine pancreas responds poorly to most conventional anti-cancer agents , and new agents are required to palliate this disease . Seocalcitol ( EB1089 ) , a vitamin D analogue , can inhibit growth , induce differentiation and induce apoptosis of cancer cell lines in vitro and can also inhibit growth of pancreatic cancer xenografts in vivo . Thirty-six patients with advanced pancreatic cancer received once daily oral treatment with seocalcitol with dose escalation every 2 weeks until hypercalcaemia occurred , following which patients continued with maintenance therapy . The most frequent toxicity was the anticipated dose-dependent hypercalcaemia , with most patients tolerating a dose of 10–15 μg per day in chronic administration . Fourteen patients completed at least 8 weeks of treatment and were evaluable for efficacy , whereas 22 patients were withdrawn prior to completing 8 weeks ' treatment and in 20 of these patients withdrawal was due to clinical deterioration as a result of disease progression . No objective responses were observed , with five of 14 patients having stable disease in whom the duration of stable disease was 82–532 days ( median=168 days ) . The time to treatment failure ( n=36 ) ranged from 22 to 847 days , and with a median survival of approximately 100 days . Seocalcitol is well tolerated in pancreatic cancer but has no objective anti-tumour activity in advanced disease . Further studies are necessary to determine if this agent has any cytostatic activity in this malignancy in minimal disease states BACKGROUND Nivolumab ( a programmed death 1 [ PD-1 ] checkpoint inhibitor ) and ipilimumab ( a cytotoxic T-lymphocyte-associated antigen 4 [ CTLA-4 ] checkpoint inhibitor ) have been shown to have complementary activity in metastatic melanoma . In this r and omized , double-blind , phase 3 study , nivolumab alone or nivolumab plus ipilimumab was compared with ipilimumab alone in patients with metastatic melanoma . METHODS We assigned , in a 1:1:1 ratio , 945 previously untreated patients with unresectable stage III or IV melanoma to nivolumab alone , nivolumab plus ipilimumab , or ipilimumab alone . Progression-free survival and overall survival were co primary end points . Results regarding progression-free survival are presented here . RESULTS The median progression-free survival was 11.5 months ( 95 % confidence interval [ CI ] , 8.9 to 16.7 ) with nivolumab plus ipilimumab , as compared with 2.9 months ( 95 % CI , 2.8 to 3.4 ) with ipilimumab ( hazard ratio for death or disease progression , 0.42 ; 99.5 % CI , 0.31 to 0.57 ; P<0.001 ) , and 6.9 months ( 95 % CI , 4.3 to 9.5 ) with nivolumab ( hazard ratio for the comparison with ipilimumab , 0.57 ; 99.5 % CI , 0.43 to 0.76 ; P<0.001 ) . In patients with tumors positive for the PD-1 lig and ( PD-L1 ) , the median progression-free survival was 14.0 months in the nivolumab-plus-ipilimumab group and in the nivolumab group , but in patients with PD-L1-negative tumors , progression-free survival was longer with the combination therapy than with nivolumab alone ( 11.2 months [ 95 % CI , 8.0 to not reached ] vs. 5.3 months [ 95 % CI , 2.8 to 7.1 ] ) . Treatment-related adverse events of grade 3 or 4 occurred in 16.3 % of the patients in the nivolumab group , 55.0 % of those in the nivolumab-plus-ipilimumab group , and 27.3 % of those in the ipilimumab group . CONCLUSIONS Among previously untreated patients with metastatic melanoma , nivolumab alone or combined with ipilimumab result ed in significantly longer progression-free survival than ipilimumab alone . In patients with PD-L1-negative tumors , the combination of PD-1 and CTLA-4 blockade was more effective than either agent alone . ( Funded by Bristol-Myers Squibb ; CheckMate 067 Clinical Trials.gov number , NCT01844505 . ) Objective : nab-Paclitaxel has been shown to disrupt pancreatic cancer stroma and was effective in combination with gemcitabine in a phase I/II trial . This study was design ed to determine the efficacy of nab-paclitaxel monotherapy in previously treated pancreatic cancer patients . Methods : In this phase II trial , patients with advanced pancreatic cancer who progressed on gemcitabine-based therapy , received nab-paclitaxel 100 mg/m2 over 30 minutes on days 1 , 8 , and 15 of a 28-day cycle . The primary endpoint was 6-month overall survival ( OS ) . Secondary endpoints were response rate ( by Response Evaluation Criteria In Solid Tumors ) , progression-free survival , safety , and toxicity profile . Results : Among 19 patients treated , the median age was 61 years , 9 ( 47 % ) were male patients and 18 ( 95 % ) had stage-IV disease . The primary endpoint of the study was reached with a 6-month OS of 58 % [ 95 % confidence interval ( 95 % CI ) , 33%-76 % ] and an estimated median OS of 7.3 months ( 95 % CI , 2.8 - 15.8 mo ) . The median progression-free survival was 1.7 months ( 95 % CI , 1.5 - 3.5 mo ) . One patient had a confirmed partial response and 6 ( 32 % ) had stable disease as their best response . Nonhematological toxicities were generally mild with grade s 1 - 2 nausea , anorexia , hypocalcemia , and vomiting occurring in 63 % , 47 % , 37 % , and 26 % of patients , respectively . Grade s 3 - 4 neutropenia , neutropenic fever , and anemia occurred in 32 % , 11 % , and 11 % of patients , respectively . Only 2 of 15 available tumors stained positive for secreted protein acid rich in cysteine , and neither of these patients benefited from the therapy . Conclusions : nab-Paclitaxel was well tolerated , and it demonstrated preliminary evidence of activity in a subset of patients who progressed on gemcitabine-based therapy BACKGROUND Axitinib ( AG-013736 ) is a potent and selective oral inhibitor of vascular endothelial growth factor receptors 1 , 2 , and 3 , which have an important role in pancreatic cancer . The aim of this study was to assess the safety and efficacy of gemcitabine plus axitinib versus gemcitabine alone . METHODS Between January and August , 2006 , 103 patients with unresectable , locally advanced , or metastatic pancreatic cancer were r and omly assigned in a two to one ratio to receive gemcitabine ( 1000 mg/m(2 ) ) plus axitinib 5 mg twice daily ( n=69 ) or gemcitabine ( 1000 mg/m(2 ) ) alone ( n=34 ) by a central ised registration system . The primary endpoint was overall survival . Analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00219557 . FINDINGS All r and omised patients were included in the efficacy analyses . Median overall survival was longer with gemcitabine plus axitinib than with gemcitabine alone ( 6.9 [ 95 % CI 5.3 - 10.1 ] months vs 5.6 [ 3.9 - 8.8 ] months ) . The hazard ratio for survival with gemcitabine plus axitinib versus with gemcitabine alone , adjusted for stratification factors , was 0.71 ( 95 % CI 0.44 - 1.13 ) . The most common grade 3 or worse adverse events were fatigue ( 15 [ 22 % ] patients in the gemcitabine plus axitinib group vs one [ 3 % ] in the gemcitabine alone group ) , abdominal pain ( eight [ 12 % ] vs five [ 16 % ] ) , and asthenia ( eight [ 12 % ] vs one [ 3 % ] ) . INTERPRETATION Gemcitabine plus axitinib showed a similar safety profile to gemcitabine alone ; the small , non-statistically significant gain in overall survival needs to be assessed in a r and omised phase III trial BACKGROUND Axitinib is a potent , selective inhibitor of vascular endothelial growth factor ( VEGF ) receptors 1 , 2 , and 3 . A r and omised phase 2 trial of gemcitabine with or without axitinib in advanced pancreatic cancer suggested increased overall survival in axitinib-treated patients . On the basis of these results , we aim ed to assess the effect of treatment with gemcitabine plus axitinib on overall survival in a phase 3 trial . METHODS In this double-blind , placebo-controlled , phase 3 study , eligible patients had metastatic or locally advanced pancreatic adenocarcinoma , no uncontrolled hypertension or venous thrombosis , and Eastern Cooperative Oncology Group performance status 0 or 1 . Patients , stratified by disease extent ( metastatic vs locally advanced ) , were r and omly assigned ( 1:1 ) to receive gemcitabine 1000 mg/m(2 ) intravenously on days 1 , 8 , and 15 every 28 days plus either axitinib or placebo . Axitinib or placebo were administered orally with food at a starting dose of 5 mg twice a day , which could be dose-titrated up to 10 mg twice daily if well tolerated . A central ised r and omisation procedure was used to assign patients to each treatment group , with r and omised permuted blocks within strata . Patients , investigators , and the trial sponsor were masked to treatment assignments . The primary endpoint was overall survival . All efficacy analyses were done in all patients assigned to treatment groups for whom data were available ; safety and treatment administration and compliance assessment s were based on treatment received . This study is registered at Clinical Trials.gov , number NCT00471146 . FINDINGS Between July 27 , 2007 , and Oct 31 , 2008 , 632 patients were enrolled and assigned to treatment groups ( 316 axitinib , 316 placebo ) . At an interim analysis in January , 2009 , the independent data monitoring committee concluded that the futility boundary had been crossed . Median overall survival was 8·5 months ( 95 % CI 6·9 - 9·5 ) for gemcitabine plus axitinib ( n=314 , data missing for two patients ) and 8·3 months ( 6·9 - 10·3 ) for gemcitabine plus placebo ( n=316 ; hazard ratio 1·014 , 95 % CI 0·786 - 1·309 ; one-sided p=0·5436 ) . The most common grade 3 or higher adverse events for gemcitabine plus axitinib and gemcitabine plus placebo were hypertension ( 20 [ 7 % ] and 5 [ 2 % ] events , respectively ) , abdominal pain ( 20 [ 7 % ] and 17 [ 6 % ] ) , fatigue ( 27 [ 9 % ] and 21 [ 7 % ] ) , and anorexia ( 19 [ 6 % ] and 11 [ 4 % ] ) . INTERPRETATION The addition of axitinib to gemcitabine does not improve overall survival in advanced pancreatic cancer . These results add to increasing evidence that targeting of VEGF signalling is an ineffective strategy in this disease . FUNDING Pfizer 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 . ) BACKGROUND Targeting platelet-derived growth factor receptor-β ( PDGFR-β ) is a potential strategy to reduce tumour-related interstitial fluid pressure , enhance cytotoxic drug uptake and reduce chemoresistance . This study aim ed to define safe doses of gemcitabine plus oxaliplatin when combined with imatinib ( potent PDGFR-β inhibitor ) in patients with advanced gemcitabine-refractory pancreatic cancer ( PC ) . PATIENTS AND METHODS Using a 3 + 3 dose escalation design , patients of performance status zero or one were entered into five sequential dose levels ( DLs ) of gemcitabine [ day 1 , from 400 ( DL1 ) to 1000 mg/m(2 ) ( DL4 ) ] and oxaliplatin [ day 2 , 85 ( DL1 - 4 ) and 100 mg/m(2 ) ( DL5 ) ] two weekly . Imatinib 400 mg od was given for 7 days ( day minus 2 - 5 ) each cycle . RESULTS Twenty-seven patients received 168 cycles in total . Median age was 61 years ( 44 - 74 years ) . Dose-limiting toxicities occurred in two of two patients at DL5 ( G4 thrombocytopenia , G3 lethargy ) , defined as the maximum tolerated dose and one of six patients at DL4 ( G3 lethargy ) . DL4 was exp and ed . There were 2 of 27 partial responses and 14 of 27 stable disease [ disease control 52 % , 95 % confidence interval ( CI ) 32 % to 71 % ] . Median progression-free survival and overall survival were 4.6 ( 95 % CI 2.1 - 7.0 ) and 5.6 months ( 95 % CI 2.5 - 8.7 ) , respectively . CONCLUSION In gemcitabine-refractory PC , gemcitabine ( 1000 mg/m(2 ) ) and oxaliplatin ( 85 mg/m(2 ) ) can be safely combined with imatinib given on a 7 days on and 7 days off intermittent schedule Purpose : This phase I study investigated the maximum-tolerated dose ( MTD ) , safety , pharmacodynamics , immunologic correlatives , and antitumor activity of CP-870,893 , an agonist CD40 antibody , when administered in combination with gemcitabine in patients with advanced pancreatic ductal adenocarcinoma ( PDA ) . Experimental Design : Twenty-two patients with chemotherapy-naïve advanced PDA were treated with 1,000 mg/m2 gemcitabine once weekly for three weeks with infusion of CP-870,893 at 0.1 or 0.2 mg/kg on day three of each 28-day cycle . Results : CP-870,893 was well-tolerated ; one dose-limiting toxicity ( grade 4 , cerebrovascular accident ) occurred at the 0.2 mg/kg dose level , which was estimated as the MTD . The most common adverse event was cytokine release syndrome ( grade 1 to 2 ) . CP-870,893 infusion triggered immune activation marked by an increase in inflammatory cytokines , an increase in B-cell expression of costimulatory molecules , and a transient depletion of B cells . Four patients achieved a partial response ( PR ) . 2-[18F]fluoro-2-deoxy-d-glucose-positron emission tomography/computed tomography ( FDG-PET/CT ) showed more than 25 % decrease in FDG uptake within primary pancreatic lesions in six of eight patients ; however , responses observed in metastatic lesions were heterogeneous , with some lesions responding with complete loss of FDG uptake , whereas other lesions in the same patient failed to respond . Improved overall survival correlated with a decrease in FDG uptake in hepatic lesions ( R = −0.929 ; P = 0.007 ) . Conclusions : CP-870,893 in combination with gemcitabine was well-tolerated and associated with antitumor activity in patients with PDA . Changes in FDG uptake detected on PET/CT imaging provide insight into therapeutic benefit . Phase II studies are warranted . Clin Cancer Res ; 19(22 ) ; 6286–95 . © 2013 AACR PURPOSE The combination of gemcitabine plus bevacizumab produced a 21 % response rate and a median survival of 8.8 months in a multicenter phase II trial in patients with metastatic pancreatic cancer . These encouraging data led Cancer and Leukemia Group B ( CALGB ) to conduct a double-blind , placebo-controlled , r and omized phase III trial of gemcitabine/bevacizumab versus gemcitabine/placebo in advanced pancreatic cancer patients . PATIENTS AND METHODS Eligible patients had no prior therapy for advanced disease , Eastern Cooperative Oncology Group ( ECOG ) performance status 0 to 2 , no tumor invasion of adjacent organs , and no increased bleeding risk . The primary end point was overall survival . Patients were stratified by performance status , extent of disease , and prior radiotherapy . Patients received gemcitabine at 1,000 mg/m(2 ) over 30 minutes on days 1 , 8 , and 15 every 28 days and bevacizumab at 10 mg/kg or placebo on days 1 and 15 every 28 days . RESULTS Between June 2004 and April 2006 , 602 patients were enrolled onto the study and 535 were treated . Median overall survival was 5.8 months for gemcitabine/bevacizumab and 5.9 months for gemcitabine/placebo ( P = .95 ) . Median progression-free survival was 3.8 and 2.9 months , respectively ( P = .07 ) . Overall response rates were 13 % and 10 % , respectively . Patients with a performance status of 0 , 1 , and 2 survived a median of 7.9 , 4.8 , and 2.4 months , respectively . The only statistically significant differences in grade s 3 and 4 toxicity occurred for hypertension ( 10 % v 3 % ; P < .001 ) and proteinuria ( 5 % v 1 % ; P = .002 ) ; venous thrombosis grade > or = 3 was equivalent in both arms ( 14 % and 15 % , respectively ) . CONCLUSION The addition of bevacizumab to gemcitabine does not improve survival in advanced pancreatic cancer patients Imatinib targets KIT and platelet-derived growth factor receptors ( PDGFR ) and is highly effective in the treatment of CML and GIST patients . Pancreatic cancers express KIT and PDGFRs . Therefore , 26 patients with unresectable pancreatic cancer were r and omized to either gemcitabine ( 1000 mg/m2 weekly ) or imatinib ( 2x400 mg po ) treatment daily . Pancreatic adenocarcinoma was confirmed histologically and expression of KIT and PDGFRbeta was determined immunohistochemically in the biopsy specimens . Quality of life was assessed with two st and ard question naires . No objective responses were seen in either group . Median time to progression was 77 and 29 days ( P=0.411 ) and median survival time was 140 and 60 days ( P=0.517 ) for gemcitabine and imatinib , respectively . Survival and treatment responses were independent of KIT and PDGFRbeta expression in patients treated with imatinib . Grade 3/4 toxicities of imatinib treatment were anemia , elevated liver enzymes , vomiting , and dyspnea . Patients treated with imatinib reported diarrhoea and /or altered bowel function more frequently , which were treatable symptomatically . Quality of life was similar in both groups . In this small series of pancreatic cancer patients , treatment with imatinib was not associated with a significant control of cancer progression We previously conducted a phase I clinical trial combining the HLA‐A*2402‐restricted KIF20A‐derived peptide vaccine with gemcitabine for advanced pancreatic cancer ( PC ) and confirmed its safety and immunogenicity in cancer patients . In this study , we conducted a multicenter , single‐armed , phase II trial using two antiangiogenic cancer vaccines targeting VEGFR1 and VEGFR2 in addition to the KIF20A peptide . We attempted to evaluate the clinical benefit of the cancer vaccination in combination with gemcitabine . Chemotherapy naïve PC patients were enrolled to evaluate primarily the 1‐year survival rate , and secondarily overall survival ( OS ) , progression free survival ( PFS ) , response rate ( RR ) , disease control rate ( DCR ) and the peptide‐specific immune responses . All enrolled patients received therapy without the HLA‐A information , and the HLA genotypes were used for classification of the patients . Between June 2012 and May 2013 , a total of 68 patients were enrolled . No severe systemic adverse effects of Grade 3 or higher related to these three peptides were observed . The 1‐year survival rates between the HLA‐A*2402‐matched and ‐unmatched groups were not significantly different . In the HLA‐A*2402 matched group , patients showing peptide‐specific CTL induction for KIF20A or VEGFR1 showed a better prognosis compared to those without such induction ( P = 0.023 , P = 0.009 , respectively ) . In the HLA‐A*2402‐matched group , the patients who showed a strong injection site reaction had a better survival rate ( P = 0.017 ) compared to those with a weak or no injection site reaction . This phase II study demonstrated that this therapeutic peptide cocktail might be effective in patients who demonstrate peptide‐specific immune reactions although predictive biomarkers are needed for patient selection in its further clinical application Summary Background Our retrospective study and phase I trial of gemcitabine and c and esartan combination therapy suggested the inhibition of renin-angiotensin system potentially has a role in the treatment of advanced pancreatic cancer . The aim of this multicenter phase II trial was to assess the efficacy and toxicity of gemcitabine and c and esartan combination therapy for advanced pancreatic cancer . Methods Chemotherapy-naive patients with histologically or cytologically proven advanced pancreatic cancer were enrolled . Gemcitabine was administered at a dose of 1,000 mg/m2 over 30 min on days 1 , 8 , and 15 and oral c and esartan at a dose of 16 mg in normotensive patients , and 8 mg initially in hypertensive patients , with dose escalation to 16 mg allowed , from days 1 to 28 , repeated every 4 weeks . Results A total of 35 patients with advanced pancreatic cancer were enrolled . Overall response rate and disease control rate were 11.4 % and 62.9 % . The median PFS and OS were 4.3 and 9.1 months with 1-year survival rate of 34.2 % . The median PFS was significantly longer in patients receiving 16 mg compared with 8 mg of c and esartan ( 4.6 vs. 3.5 months , p = 0.031 ) . Major severe toxicities were neutropenia ( 23 % ) , leukopenia ( 17 % ) and thrombocytopenia ( 11 % ) . Grade 2 hypotension was observed in 3 patients ( 9 % ) and c and esartan was discontinued in 2 patients due to hypotension . Conclusions In this multicenter phase 2 trial , gemcitabine and c and esartan combination therapy was tolerable but failed to demonstrate activity against advanced pancreatic cancer . ( UMIN CTR : UMIN000005580 Vascular endothelial growth factor receptor 2 ( VEGFR2 ) is an essential factor in tumor angiogenesis and in the growth of pancreatic cancer . Immunotherapy using epitope peptide for VEGFR2 ( VEGFR2‐169 ) that we identified previously is expected to improve the clinical outcome . Therefore , a phase I clinical trial combining of VEGFR2‐169 with gemcitabine was conducted for patients with advanced pancreatic cancer . Patients with metastatic and unresectable pancreatic cancer were eligible for the trial . Gemcitabine was administered at a dose of 1000 mg/m2 on days 1 , 8 , and 15 in a 28‐day cycle . The VEGFR2‐169 peptide was subcutaneously injected weekly in a dose‐escalation manner ( doses of 0.5 , 1 , and 2 mg/body , six patients /one cohort ) . Safety and immunological parameters were assessed . No severe adverse effect of grade 4 or higher was observed . Of the 18 patients who completed at least one course of the treatment , 15 ( 83 % ) developed immunological reactions at the injection sites . Specific cytotoxic T lymphocytes ( CTL ) reacting to the VEGFR2‐169 peptide were induced in 11 ( 61 % ) of the 18 patients . The disease control rate was 67 % , and the median overall survival time was 8.7 months . This combination therapy for pancreatic cancer patients was tolerable at all doses . Peptide‐specific CTL could be induced by the VEGFR2‐169 peptide vaccine at a high rate , even in combination with gemcitabine . From an immunological point of view , the optimal dose for further clinical trials might be 2 mg/body or higher . This trial was registered with Clinical Trial.gov ( no. NCT 00622622 ) . ( Cancer Sci 2009 Purpose : This phase Ib study evaluated the safety and tolerability of PEGylated human recombinant hyaluronidase ( PEGPH20 ) in combination with gemcitabine ( Gem ) , and established a phase II dose for patients with untreated stage IV metastatic pancreatic ductal adenocarcinoma ( PDA ) . Objective response rate and treatment efficacy using biomarker and imaging measurements were also evaluated . Experimental Design : Patients received escalating intravenous doses of PEGPH20 in combination with Gem using a st and ard 3 + 3 dose-escalation design . In cycle 1 ( 8 weeks ) , PEGPH20 was administrated twice weekly for 4 weeks , then once weekly for 3 weeks ; Gem was administrated once weekly for 7 weeks , followed by 1 week off treatment . In each subsequent 4-week cycle , PEGPH20 and Gem were administered once weekly for 3 weeks , followed by 1 week off . Dexamethasone ( 8 mg ) was given pre- and post-PEGPH20 administration . Several safety parameters were evaluated . Results : Twenty-eight patients were enrolled and received PEGPH20 at 1.0 ( n = 4 ) , 1.6 ( n = 4 ) , or 3.0 μg/kg ( n = 20 ) , respectively . The most common PEGPH20-related adverse events were musculoskeletal and extremity pain , peripheral edema , and fatigue . The incidence of thromboembolic events was 29 % . Median progression-free survival ( PFS ) and overall survival ( OS ) rates were 5.0 and 6.6 months , respectively . In 17 patients evaluated for pretreatment tissue hyaluronan ( HA ) levels , median PFS and OS rates were 7.2 and 13.0 months for “ high”-HA patients ( n = 6 ) , and 3.5 and 5.7 months for “ low”-HA patients ( n = 11 ) , respectively . Conclusions : PEGPH20 in combination with Gem was well tolerated and may have therapeutic benefit in patients with advanced PDA , especially in those with high HA tumors . Clin Cancer Res ; 22(12 ) ; 2848–54 . © 2016 AACR BACKGROUND Paclitaxel embedded in cationic liposomes ( EndoTAG ™ -1 ; ET ) is an innovative agent targeting tumor endothelial cells . This r and omized controlled phase II trial evaluated the safety and efficacy of ET in combination with gemcitabine ( GEM ) in advanced pancreatic cancer ( PDAC ) . PATIENTS AND METHODS Chemotherapy-naive patients with locally advanced or metastatic disease were r and omly assigned to receive weekly GEM 1000 mg/m(2 ) or GEM plus twice-weekly ET 11 , 22 or 44 mg/m(2 ) for 7 weeks . After a safety run-in of 100 patients , a second cohort continued treatment . End points included overall survival ( OS ) , progression-free survival ( PFS ) , tumor response and safety . RESULTS Two hundred and twelve patients were r and omly allocated to the study and 200 were treated ( 80 % metastatic , 20 % locally advanced ) . Adverse events were manageable and reversible . Transient thrombocytopenia and infusion reactions with chills and pyrexia mostly grade 1 or 2 occurred in the ET groups . Disease control rate after the first treatment cycle was 43 % with GEM and 60 % , 65 % and 52 % in the GEM + ET cohorts . Median PFS reached 2.7 compared with 4.1 , 4.6 and 4.4 months , respectively . Median OS was 6.8 compared with 8.1 , 8.7 and 9.3 months , respectively . CONCLUSIONS Treatment of advanced PDAC with GEM + ET was generally well tolerated . GEM + ET showed beneficial survival and efficacy . A r and omized phase III trial should confirm this positive trend Phase 3 studies of bevacizumab in patients with advanced pancreatic cancer ( APCA ) demonstrated no improvement in outcome . To the authors ' knowledge , no vali date d predictive biomarkers for bevacizumab exist , although emerging data suggest that subsets of patients with APCA may benefit from treatment with bevacizumab . The authors evaluated baseline serum albumin ( b‐alb ) as a predictive biomarker in a pooled analysis from 7 prospect i ve clinical trials of gemcitabine‐based therapy with or without bevacizumab PURPOSE Patients with advanced pancreatic cancer have a poor prognosis and there have been no improvements in survival since the introduction of gemcitabine in 1996 . Pancreatic tumors often overexpress human epidermal growth factor receptor type 1 ( HER1/EGFR ) and this is associated with a worse prognosis . We studied the effects of adding the HER1/EGFR-targeted agent erlotinib to gemcitabine in patients with unresectable , locally advanced , or metastatic pancreatic cancer . PATIENTS AND METHODS Patients were r and omly assigned 1:1 to receive st and ard gemcitabine plus erlotinib ( 100 or 150 mg/d orally ) or gemcitabine plus placebo in a double-blind , international phase III trial . The primary end point was overall survival . RESULTS A total of 569 patients were r and omly assigned . Overall survival based on an intent-to-treat analysis was significantly prolonged on the erlotinib/gemcitabine arm with a hazard ratio ( HR ) of 0.82 ( 95 % CI , 0.69 to 0.99 ; P = .038 , adjusted for stratification factors ; median 6.24 months v 5.91 months ) . One-year survival was also greater with erlotinib plus gemcitabine ( 23 % v 17 % ; P = .023 ) . Progression-free survival was significantly longer with erlotinib plus gemcitabine with an estimated HR of 0.77 ( 95 % CI , 0.64 to 0.92 ; P = .004 ) . Objective response rates were not significantly different between the arms , although more patients on erlotinib had disease stabilization . There was a higher incidence of some adverse events with erlotinib plus gemcitabine , but most were grade 1 or 2 . CONCLUSION To our knowledge , this r and omized phase III trial is the first to demonstrate statistically significantly improved survival in advanced pancreatic cancer by adding any agent to gemcitabine . The recommended dose of erlotinib with gemcitabine for this indication is 100 mg/d BACKGROUND Pre clinical data support the combined inhibition of vascular endothelial growth factor ( VEGF ) and epidermal growth factor receptor ( EGFR ) pathways in the treatment of pancreatic cancer . Following a dose finding phase I study the efficacy and toxicity of a four-drug regimen utilising the cytotoxic doublet of gemcitabine and capecitabine ( GemCap ) , with the biological doublet of erlotinib and bevacizumab were further assessed in patients with advanced pancreatic cancer . PATIENTS AND METHODS In a phase II expansion cohort , patients with chemonaive locally advanced or metastatic pancreatic cancer received gemcitabine ( 1000mg/m(2 ) D1 , 8 , 15 ) , capecitabine ( 1400mg/m(2 ) D1 - 21 ) , erlotinib ( 100 mg daily ) and bevacizumab ( 5mg/kg D1 , 15 ) every 28days . The primary endpoint was radiological response rate by response evaluation criteria in solid tumours ( RECIST ) . Computed tomography ( CT ) assessment was performed every 8weeks . Consolidation radiotherapy was considered in locally advanced patients following six cycles of treatment . RESULTS In total 44 patients ( phases I & II ) were recruited . The median cycles delivered were 6 ( range 1 - 16 ) . Confirmed radiological responses were seen in 23 % ( 95 % confidence interval ( CI ) : 11 - 38 % ) of patients . The median progression-free and overall survival for the entire cohort was 8.4 and 12.6months , respectively . In patients with metastatic disease the median overall survival was 10.1months . Common grade 3/4 toxicities were ; neutropenia 52 % , lethargy 32 % , diarrhoea 18 % and h and -foot syndrome 18 % . CONCLUSION The combination of gemcitabine , capecitabine , erlotinib and bevacizumab was feasible with a manageable toxicity profile and demonstrated encouraging efficacy data in a good performance status population PURPOSE Vascular endothelial growth factor ( VEGF ) plays a key role in the biology and prognosis of pancreatic cancer . Inhibitors of VEGF suppress the growth of pancreatic cancer in pre clinical models . The objectives of this phase II study were to assess the response rate and overall survival of pancreatic cancer patients who received gemcitabine with the recombinant humanized anti-VEGF monoclonal antibody bevacizumab . PATIENTS AND METHODS Patients with previously untreated advanced pancreatic cancer received gemcitabine 1,000 mg/m(2 ) intravenously over 30 minutes on days 1 , 8 , and 15 every 28 days . Bevacizumab , 10 mg/kg , was administered after gemcitabine on days 1 and 15 . Tumor measurements were assessed every two cycles . Plasma VEGF levels were obtained pretreatment . RESULTS Fifty-two patients were enrolled at seven centers between November 2001 and March 2004 . All patients had metastatic disease , and 83 % had liver metastases . Eleven patients ( 21 % ) had confirmed partial responses , and 24 ( 46 % ) had stable disease . The 6-month survival rate was 77 % . Median survival was 8.8 months ; median progression-free survival was 5.4 months . Pretreatment plasma VEGF levels did not correlate with outcome . Grade 3 and 4 toxicities included hypertension in 19 % of the patients , thrombosis in 13 % , visceral perforation in 8 % , and bleeding in 2 % . CONCLUSION The combination of bevacizumab plus gemcitabine is active in advanced pancreatic cancer patients . Additional study is warranted . A r and omized phase III trial of gemcitabine plus bevacizumab versus gemcitabine plus placebo is ongoing in the Cancer and Leukemia Group BACKGROUND Nivolumab , a programmed death 1 ( PD-1 ) checkpoint inhibitor , was associated with encouraging overall survival in uncontrolled studies involving previously treated patients with advanced renal-cell carcinoma . This r and omized , open-label , phase 3 study compared nivolumab with everolimus in patients with renal-cell carcinoma who had received previous treatment . METHODS A total of 821 patients with advanced clear-cell renal-cell carcinoma for which they had received previous treatment with one or two regimens of antiangiogenic therapy were r and omly assigned ( in a 1:1 ratio ) to receive 3 mg of nivolumab per kilogram of body weight intravenously every 2 weeks or a 10-mg everolimus tablet orally once daily . The primary end point was overall survival . The secondary end points included the objective response rate and safety . RESULTS The median overall survival was 25.0 months ( 95 % confidence interval [ CI ] , 21.8 to not estimable ) with nivolumab and 19.6 months ( 95 % CI , 17.6 to 23.1 ) with everolimus . The hazard ratio for death with nivolumab versus everolimus was 0.73 ( 98.5 % CI , 0.57 to 0.93 ; P=0.002 ) , which met the prespecified criterion for superiority ( P≤0.0148 ) . The objective response rate was greater with nivolumab than with everolimus ( 25 % vs. 5 % ; odds ratio , 5.98 [ 95 % CI , 3.68 to 9.72 ] ; P<0.001 ) . The median progression-free survival was 4.6 months ( 95 % CI , 3.7 to 5.4 ) with nivolumab and 4.4 months ( 95 % CI , 3.7 to 5.5 ) with everolimus ( hazard ratio , 0.88 ; 95 % CI , 0.75 to 1.03 ; P=0.11 ) . Grade 3 or 4 treatment-related adverse events occurred in 19 % of the patients receiving nivolumab and in 37 % of the patients receiving everolimus ; the most common event with nivolumab was fatigue ( in 2 % of the patients ) , and the most common event with everolimus was anemia ( in 8 % ) . CONCLUSIONS Among patients with previously treated advanced renal-cell carcinoma , overall survival was longer and fewer grade 3 or 4 adverse events occurred with nivolumab than with everolimus . ( Funded by Bristol-Myers Squibb ; CheckMate 025 Clinical Trials.gov number , NCT01668784 . ) PURPOSE The trial objectives were to identify the maximum-tolerated dose ( MTD ) of first-line gemcitabine plus nab-paclitaxel in metastatic pancreatic adenocarcinoma and to provide efficacy and safety data . Additional objectives were to evaluate positron emission tomography ( PET ) scan response , secreted protein acidic and rich in cysteine ( SPARC ) , and CA19 - 9 levels in relation to efficacy . Subsequent pre clinical studies investigated the changes involving the pancreatic stroma and drug uptake . PATIENTS AND METHODS Patients with previously untreated advanced pancreatic cancer were treated with 100 , 125 , or 150 mg/m(2 ) nab-paclitaxel followed by gemcitabine 1,000 mg/m(2 ) on days 1 , 8 , and 15 every 28 days . In the pre clinical study , mice were implanted with human pancreatic cancers and treated with study agents . RESULTS A total of 20 , 44 , and three patients received nab-paclitaxel at 100 , 125 , and 150 mg/m(2 ) , respectively . The MTD was 1,000 mg/m(2 ) of gemcitabine plus 125 mg/m(2 ) of nab-paclitaxel once a week for 3 weeks , every 28 days . Dose-limiting toxicities were sepsis and neutropenia . At the MTD , the response rate was 48 % , with 12.2 median months of overall survival ( OS ) and 48 % 1-year survival . Improved OS was observed in patients who had a complete metabolic response on [(18)F]fluorodeoxyglucose PET . Decreases in CA19 - 9 levels were correlated with increased response rate , progression-free survival , and OS . SPARC in the stroma , but not in the tumor , was correlated with improved survival . In mice with human pancreatic cancer xenografts , nab-paclitaxel alone and in combination with gemcitabine depleted the desmoplastic stroma . The intratumoral concentration of gemcitabine was increased by 2.8-fold in mice receiving nab-paclitaxel plus gemcitabine versus those receiving gemcitabine alone . CONCLUSION The regimen of nab-paclitaxel plus gemcitabine has tolerable adverse effects with substantial antitumor activity , warranting phase III evaluation |
12,189 | 30,323,649 | There is also promising support for the cost-effectiveness of ACT ; however , the current evidence is still insufficient to establish firm conclusions about cost-effectiveness and the most efficient means of delivery . | It is well known that chronic pain is prevalent , complex to manage , and associated with high costs , in health care and society in general .
Thanks to advances in new forms of cognitive behavioral therapy ( known as third-wave CBT ) , currently clinicians and research ers have an empirically vali date d psychological treatment with increasing research support for the treatment of chronic pain .
This treatment is called acceptance and commitment therapy ( ACT ) .
The main aim of this paper is to provide a narrative review that summarizes and integrates the current state of knowledge of ACT in the management of chronic pain as well as discuss current challenges and opportunities for progress .
Based on the psychological flexibility model , ACT extends previous forms of CBT and integrates many CBT-related variables into six core therapeutic processes .
ACT is a process-based therapy that fosters openness , awareness , and engagement through a wide range of methods , including exposure-based and experiential methods , metaphors , and values clarification . | Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular , but to date little is known about neural mechanisms associated with these interventions . Mindfulness-Based Stress Reduction ( MBSR ) , one of the most widely used mindfulness training programs , has been reported to produce positive effects on psychological well-being and to ameliorate symptoms of a number of disorders . Here , we report a controlled longitudinal study to investigate pre-post changes in brain gray matter concentration attributable to participation in an MBSR program . Anatomical magnetic resonance ( MR ) images from 16 healthy , meditation-naïve participants were obtained before and after they underwent the 8-week program . Changes in gray matter concentration were investigated using voxel-based morphometry , and compared with a waiting list control group of 17 individuals . Analyses in a priori regions of interest confirmed increases in gray matter concentration within the left hippocampus . Whole brain analyses identified increases in the posterior cingulate cortex , the temporo-parietal junction , and the cerebellum in the MBSR group compared with the controls . The results suggest that participation in MBSR is associated with changes in gray matter concentration in brain regions involved in learning and memory processes , emotion regulation , self-referential processing , and perspective taking Introduction Internet-delivered psychological interventions among people with chronic pain have the potential to overcome environmental and economic barriers to the provision of evidence -based psychological treatment in the Irish health service context . While the use of internet-delivered cognitive – behavioural therapy programmes has been consistently shown to have small-to-moderate effects in the management of chronic pain , there is a paucity in the research regarding the effectiveness of an internet-delivered Acceptance and Commitment Therapy ( ACT ) programme among people with chronic pain . The current study will compare the clinical -effectiveness and cost-effectiveness of an online ACT intervention with a waitlist control condition in terms of the management of pain-related functional interference among people with chronic pain . Methods and analysis Participants with non-malignant pain that persists for at least 3 months will be r and omised to one of two study conditions . The experimental group will undergo an eight-session internet-delivered ACT programme over an 8-week period . The control group will be a waiting list group and will be offered the ACT intervention after the 3-month follow-up period . Participants will be assessed preintervention , postintervention and at a 3-month follow-up . The primary outcome will be pain-related functional interference . Secondary outcomes will include : pain intensity , depression , global impression of change , acceptance of chronic pain and quality of life . A qualitative evaluation of the perspectives of the participants regarding the ACT intervention will be completed after the trial . Ethics and dissemination The study will be performed in agreement with the Declaration of Helsinki and is approved by the National University of Irel and Galway Research Ethics Committee ( 12/05/05 ) . The results of the trial will be published according to the CONSORT statement and will be presented at conferences and reported in peer- review ed journals . Trial registration number IS RCT N18166896 Acceptance and Commitment Therapy ( ACT ) training often includes experiential elements aim ed at improving therapist psychological flexibility , yet the effects of ACT training on therapist psychological flexibility have yet to be evaluated . This pilot study examines the effects of experiential phone consultation as an adjunct to a st and ard continuing education workshop on psychological flexibility and burnout among therapists learning ACT . In this study , counselors taking a 2-day ACT workshop were r and omly assigned to either six 30-min phone consultation sessions ( n = 10 ) or no additional contact ( n = 10 ) . The results show that those in the consultation condition reported higher psychological flexibility at the 3-month follow-up compared to the workshop-only condition . Improvements in ACT knowledge , overall burnout , and personal accomplishment were found in both groups , independent of whether they received phone consultation , and this increase was maintained over time . In conclusion , ACT phone consultation contributed to counselor psychological flexibility above the workshop alone and appears to be feasible as a means to improve counselor psychological flexibility Fibromyalgia Syndrome ( FMS ) is a chronic pain condition characterized by pain , fatigue , and nonrestorative sleep . The disruptive symptoms of FMS are associated with reductions in quality of life related to family , intimate relationships , and work . The present study was part of a r and omized pilot study of an 8-week Acceptance and Commitment Therapy ( ACT ) intervention compared to education in a sample of 28 women with FMS . The Chronic Pain Values Inventory was administered at baseline , postintervention , and 12 week follow-up . Both groups showed significant improvements in family success , which were maintained at follow-up . Groups showed a differential pattern of success in work . The ACT group demonstrated significant , maintained improvements in success in intimate relationships , while the education group reported no changes over time . Findings suggest that both interventions may lead to improvements in valued living ; however different interventions may be best suited for certain valued domains . The results of this study indicate that FMS patients are able to improve their success in family and intimate relationships and losses in these areas are not necessarily permanent Abstract One way to improve treatment effects of chronic pain is to identify and improve control over mechanisms of therapeutic change . One treatment approach that includes a specific proposed mechanism is acceptance and commitment therapy ( ACT ) with its focus on increasing psychological flexibility ( PF ) . The aim of the present study was to examine the role of PF as a mechanism of change in ACT . This is based on mediation analyses of data from a previously reported r and omized controlled trial , evaluating the effectiveness of an ACT-based online intervention for chronic pain ( ACTonPain ) . We performed secondary analyses on pretreatment , posttreatment , and follow-up data from 302 adults , receiving a guided ( n = 100 ) or unguided ( n = 101 ) version of ACTonPain , or allocated to the waitlist control group ( n = 101 ) . Structural equation modelling and a bias-corrected bootstrap approach were applied to examine the indirect effects of the treatment through pretreatment and posttreatment changes in the latent construct reflecting PF . The latent construct consisted of data from the Chronic Pain Acceptance Question naire and the Acceptance and Action Question naire . The outcomes were pretreatment to follow-up changes in pain interference , anxiety , depression , pain , and mental and physical health . Structural equation modelling analyses revealed that changes in PF significantly mediated pretreatment to follow-up changes in all outcomes in the intervention groups compared with waitlist ( st and ardized estimates ranged from I0.16I to I0.69I ) . Global model fit yielded modest but acceptable results . Findings are consistent with the theoretical framework behind ACT and contribute to growing evidence , supporting a focus on PF to optimize treatment effects Abstract Although cognitive – behavioral therapies ( CBT ) have been demonstrated to be effective for a variety of chronic pain problems , patients vary in their response and little is known about patient characteristics that predict or moderate treatment effects . Furthermore , although cognitive – behavioral theory posits that changes in patient beliefs and coping mediate the effects of CBT on patient outcomes , little research has systematic ally tested this . Therefore , we examined mediators , moderators , and predictors of treatment effects in a r and omized controlled trial of CBT for chronic temporom and ibular disorder ( TMD ) pain . Pre‐ to post‐treatment changes in pain beliefs ( control over pain , disability , and pain signals harm ) , catastrophizing , and self‐efficacy for managing pain mediated the effects of CBT on pain , activity interference , and jaw use limitations at one year . In individual mediator analyses , change in perceived pain control was the mediator that explained the greatest proportion of the total treatment effect on each outcome . Analyzing the mediators as a group , self‐efficacy had unique mediating effects beyond those of control and the other mediators . Patients who reported more pain sites , depressive symptoms , non‐specific physical problems , rumination , catastrophizing , and stress before treatment had higher activity interference at one year . The effects of CBT generally did not vary according to patient baseline characteristics , suggesting that all patients potentially may be helped by this therapy . The results provide further support for cognitive – behavioral models of chronic pain and point to the potential benefits of interventions to modify specific pain‐related beliefs in CBT and in other health care encounters In this study , 67 participants ( 95 % female ) with fibromyalgia ( FM ) were r and omly assigned to an online acceptance and commitment therapy ( online ACT ) and treatment as usual ( TAU ; ACT + TAU ) protocol or a TAU control condition . Online ACT + TAU participants were asked to complete 7 modules over an 8-week period . Assessment s were completed at pre-treatment , post-treatment , and 3-month follow-up periods and included measures of FM impact ( primary outcome ) , depression , pain , sleep , 6-minute walk , sit to st and , pain acceptance ( primary process variable ) , mindfulness , cognitive fusion , valued living , kinesiophobia , and pain catastrophizing . The results indicated that online ACT + TAU participants significantly improved in FM impact , relative to TAU ( P < .001 ) , with large between condition effect sizes at post-treatment ( 1.26 ) and follow-up ( 1.59 ) . Increases in pain acceptance significantly mediated these improvements ( P = .005 ) . Significant improvements in favor of online ACT + TAU were also found on measures of depression ( P = .02 ) , pain ( P = .01 ) , and kinesiophobia ( P = .001 ) . Although preliminary , this study highlights the potential for online ACT to be an efficacious , accessible , and cost-effective treatment for people with FM and other chronic pain conditions . PERSPECTIVE Online ACT reduced FM impact relative to a TAU control condition in this r and omized controlled trial . Reductions in FM impact were mediated by improvements in pain acceptance . Online ACT appears to be a promising intervention for FM The aim of this study was to analyze the cost utility of a group-based form of acceptance and commitment therapy ( GACT ) in patients with fibromyalgia ( FM ) compared with patients receiving recommended pharmacological treatment ( RPT ) or on a waiting list ( WL ) . The data were derived from a previously published study , a r and omized controlled trial that focused on clinical outcomes . Health economic outcomes included health-related quality of life and health care use at baseline and at 6-month follow-up using the EuroQoL and the Client Service Receipt Inventory , respectively . Analyses included quality -adjusted life years , direct and indirect cost differences , and incremental cost effectiveness ratios . A total of 156 FM patients were r and omized ( 51 GACT , 52 RPT , 53 WL ) . GACT was related to significantly less direct costs over the 6-month study period compared with both control arms ( GACT € 824.2 ± 1,062.7 vs RPT € 1,730.7 ± 1,656.8 vs WL € 2,462.7 ± 2,822.0 ) . Lower direct costs for GACT compared with RPT were due to lower costs from primary care visits and FM-related medications . The incremental cost effectiveness ratios were dominant in the completers ' analysis and remained robust in the sensitivity analyses . In conclusion , acceptance and commitment therapy appears to be a cost-effective treatment compared with RPT in patients with FM . PERSPECTIVE Decision-makers have to prioritize their budget on the treatment option that is the most cost effective for the management of a specific patient group . From government as well as health care perspectives , this study shows that a GACT is more cost effective than pharmacological treatment in management of FM Abstract Cognitive behavioral therapy ( CBT ) is believed to improve chronic pain problems by decreasing patient catastrophizing and increasing patient self-efficacy for managing pain . Mindfulness-based stress reduction ( MBSR ) is believed to benefit patients with chronic pain by increasing mindfulness and pain acceptance . However , little is known about how these therapeutic mechanism variables relate to each other or whether they are differentially impacted by MBSR vs CBT . In a r and omized controlled trial comparing MBSR , CBT , and usual care ( UC ) for adults aged 20 to 70 years with chronic low back pain ( N = 342 ) , we examined ( 1 ) baseline relationships among measures of catastrophizing , self-efficacy , acceptance , and mindfulness and ( 2 ) changes on these measures in the 3 treatment groups . At baseline , catastrophizing was associated negatively with self-efficacy , acceptance , and 3 aspects of mindfulness ( nonreactivity , nonjudging , and acting with awareness ; all P values < 0.01 ) . Acceptance was associated positively with self-efficacy ( P < 0.01 ) and mindfulness ( P values < 0.05 ) measures . Catastrophizing decreased slightly more posttreatment with MBSR than with CBT or UC ( omnibus P = 0.002 ) . Both treatments were effective compared with UC in decreasing catastrophizing at 52 weeks ( omnibus P = 0.001 ) . In both the entire r and omized sample and the sub sample of participants who attended ≥6 of the 8 MBSR or CBT sessions , differences between MBSR and CBT at up to 52 weeks were few , small in size , and of question able clinical meaningfulness . The results indicate overlap across measures of catastrophizing , self-efficacy , acceptance , and mindfulness and similar effects of MBSR and CBT on these measures among individuals with chronic low back pain Cognitive behavior therapy ( CBT ) has made important contributions to chronic pain management , but the process by which it is effective is not clear . Recently , strong arguments have been raised concerning the need for theory driven research to e.g. identify mechanisms of change in CBT and enhance the effectiveness of this type of treatment . However , the number of studies addressing these issues is still relatively scarce . Furthermore , the arrival of varieties of CBT with seemingly different process targets increases the need for such information . The present study explored the processes of change in a previously reported successful r and omized controlled trial evaluating the effectiveness of an exposure-based form of behavioral and cognitive therapy , Acceptance and Commitment Therapy ( ACT ) , on improvement in pain-related disability and life satisfaction for patients suffering from whiplash-associated disorder ( WAD ) . Several process variables relevant to theories underlying traditional CBT were included : pain , distress , kinesiophobia , self-efficacy , and the process primarily targeted by ACT : psychological inflexibility . Mediation analyses were performed using a non-parametric cross-product of the coefficients approach . Results illustrated that pain intensity , anxiety , depression , kinesiophobia , and self-efficacy did not have significant mediating effects on the dependent variables . In contrast , significant indirect effects were seen for psychological inflexibility on pain-related disability ( pre- to post-change scores ) and life satisfaction ( pre- to post ; pre- to 4-month follow-up change scores ) . Although tentative , these results support the mediating role of psychological inflexibility in ACT-oriented interventions aim ed at improving functioning and life satisfaction in people with chronic pain The subjective experience of one 's environment is constructed by interactions among sensory , cognitive , and affective processes . For centuries , meditation has been thought to influence such processes by enabling a nonevaluative representation of sensory events . To better underst and how meditation influences the sensory experience , we used arterial spin labeling functional magnetic resonance imaging to assess the neural mechanisms by which mindfulness meditation influences pain in healthy human participants . After 4 d of mindfulness meditation training , meditating in the presence of noxious stimulation significantly reduced pain unpleasantness by 57 % and pain intensity ratings by 40 % when compared to rest . A two-factor repeated- measures ANOVA was used to identify interactions between meditation and pain-related brain activation . Meditation reduced pain-related activation of the contralateral primary somatosensory cortex . Multiple regression analysis was used to identify brain regions associated with individual differences in the magnitude of meditation-related pain reductions . Meditation-induced reductions in pain intensity ratings were associated with increased activity in the anterior cingulate cortex and anterior insula , areas involved in the cognitive regulation of nociceptive processing . Reductions in pain unpleasantness ratings were associated with orbitofrontal cortex activation , an area implicated in reframing the context ual evaluation of sensory events . Moreover , reductions in pain unpleasantness also were associated with thalamic deactivation , which may reflect a limbic gating mechanism involved in modifying interactions between afferent input and executive-order brain areas . Together , these data indicate that meditation engages multiple brain mechanisms that alter the construction of the subjectively available pain experience from afferent information Aims : Cognitive and behavioral treatments ( CBT ) for sleep problems and chronic pain have shown good results , although these results could improve . More recent developments based on the psychological flexibility model , the model underlying Acceptance and Commitment Therapy ( ACT ) may offer a useful addition to traditional CBT . The aim of this study was to examine whether an ACT-based treatment for chronic pain is associated with improved sleep . Secondly , we examined the associations between changes on measures of psychological flexibility and sleep-related outcomes . Methods : The study used an observational cohort methodology . Participants were 252 patients ( 73.8 % female ) attending a 4-week , interdisciplinary , pain management program in London , United Kingdom . Participants completed st and ard self-report measures of pain and functioning , sleep outcomes , and processes of psychological flexibility . Pre- to post-treatment , and pre-treatment to follow-up measures were examined for statistically significant differences using paired sample s t-tests . Secondarily , hierarchical multiple regression analyses were conducted to examine change in process measures in relation to change in treatment outcome . Results : Participants showed statistically significant improvements ( all p < 0.001 ) at post-treatment on measures of insomnia severity ( d = 0.45 ) , sleep interference ( d = 0.61 ) , and sleep efficiency ( d = 0.32 ) . Significant improvements in insomnia severity and sleep interference were also observed at 9-month follow up . Small to medium effect sizes were observed across the sleep outcomes . Statistically significant changes were also observed on measures of psychological flexibility , and these improvements were significantly associated with improvements on sleep-related outcomes , independently contributing up to 19 % of unique variance . Conclusion : This study supports the potential usefulness of ACT-based treatments for chronic pain for addressing co-occurring sleep difficulties . Further research is needed to determine how to improve the impact of this treatment for co-morbid pain and sleep difficulties , possibly using a r and omized-controlled trial design OBJECTIVE This study compared the impact of cognitive-behavioral therapy for pain ( CBT-P ) , mindful awareness and acceptance treatment ( M ) , and arthritis education ( E ) on day-to-day pain- and stress-related changes in cognitions , symptoms , and affect among adults with rheumatoid arthritis ( RA ) . METHOD One hundred forty-three RA patients were r and omized to 1 of the 3 treatment conditions . CBT-P targeted pain-coping skills ; M targeted awareness and acceptance of current experience to enhance coping with a range of aversive experiences ; E provided information regarding RA pain and its management . At pre- and posttreatment , participants completed 30 consecutive evening diaries assessing that day 's pain , fatigue , pain-related catastrophizing and perceived control , morning disability , and serene and anxious affects . RESULTS Multilevel models compared groups in the magnitude of within-person change in daily pain and stress reactivity from pre- to posttreatment . M yielded greater reductions than did CBT-P and E in daily pain-related catastrophizing , morning disability , and fatigue and greater reductions in daily stress-related anxious affect . CBT-P yielded less pronounced declines in daily pain-related perceived control than did M and E. CONCLUSIONS For individuals with RA , M produces the broadest improvements in daily pain and stress reactivity relative to CBT-P and E. These findings also highlight the utility of a diary-based approach to evaluating the treatment-related changes in responses to daily life Patients in a low-income community health center with Type 2 diabetes ( N = 81 ) taking a one-day education workshop as part of their diabetes medical management were r and omly assigned either to education alone or to a combination of education and acceptance and commitment therapy ( ACT ) . Both groups were taught how to manage their diabetes , but those in the ACT condition also learned to apply acceptance and mindfulness skills to difficult diabetes-related thoughts and feelings . Compared with patients who received education alone , after 3 months those in the ACT condition were more likely to use these coping strategies , to report better diabetes self-care , and to have glycated hemoglobin ( HbA-sub(1C ) ) values in the target range . Mediational analyses indicated that changes in acceptance coping and self-management behavior mediated the impact of treatment on changes in HbA-sub(1C ) Summary Acceptance and commitment therapy ( ACT ) and cognitive‐behavioral therapy are both effective for pain interference and mood in chronic pain patients ; ACT may be more satisfactory . ABSTRACT Individuals reporting chronic , nonmalignant pain for at least 6 months ( N = 114 ) were r and omly assigned to 8 weekly group sessions of acceptance and commitment therapy ( ACT ) or cognitive‐behavioral therapy ( CBT ) after a 4–6 week pretreatment period and were assessed after treatment and at 6‐month follow‐up . The protocol s were design ed for use in a primary care rather than specialty pain clinic setting . All participants remained stable on other pain and mood treatments over the course of the intervention . ACT participants improved on pain interference , depression , and pain‐related anxiety ; there were no significant differences in improvement between the treatment conditions on any outcome variables . Although there were no differences in attrition between the groups , ACT participants who completed treatment reported significantly higher levels of satisfaction than did CBT participants . These findings suggest that ACT is an effective and acceptable adjunct intervention for patients with chronic pain Introduction Functional somatic syndromes ( FSS ) are common in adolescents , characterised by severe disability and reduced quality of life . Behavioural treatments such as acceptance and commitment therapy ( ACT ) has shown promising results in children and adolescents with FSS , but has focused on specific syndromes such as functional pain . The current study will compare the efficacy of group-based ACT with that of enhanced usual care ( EUC ) in adolescents with a range of FSS operationalised by the unifying construct of multiorgan bodily distress syndrome ( BDS ) . Methods and analysis A total of 120 adolescents aged 15–19 and diagnosed with multiorgan BDS , of at least 12 months duration , will be assessed and r and omised to either : ( 1 ) EUC : a manualised consultation with a child and adolescent psychiatrist and individualised treatment plan or ( 2 ) manualised ACT-based group therapy plus EUC . The ACT programme consists of 9 modules ( ie , 27 hours ) and 1 follow-up meeting ( 3 hours ) . The primary outcome is physical health , assessed by an Short Form Health Survey ( SF-36 ) aggregate score 12 months after r and omisation . Secondary outcomes include self-reported symptom severity , symptom interference , depression and anxiety , illness worry , perceived stress and global improvement ; as well as objective physical activity and bodily stress response measured by heart rate variability , hair cortisol and inflammatory biomarkers . Process measures are illness perception , illness-related behaviour and psychological flexibility . Ethics and dissemination The study is conducted in accordance with Helsinki Declaration II . Approval has been obtained from the Science Ethics Committee of the Central Denmark Region and the Danish Data Protection . The results will be sought to be published according to the CONSORT statement in peer- review ed journals . Discussion This is one of the first larger r and omised clinical trials evaluating the effect of a group-based intervention for adolescents with a range of severe FSS . Trial registration number NCT02346071 ; Pre- results Introduction Chronic low back pain ( CLBP ) is a common condition and source of significant suffering , disability and healthcare costs . Current physiotherapy treatment is moderately effective . Combining theory-based psychological methods with physiotherapy could improve outcomes for people with CLBP . The primary aim of this r and omised controlled trial ( RCT ) is to evaluate the efficacy of Physiotherapy informed by Acceptance and Commitment Therapy ( PACT ) on functioning in patients with CLBP . Methods and analysis The PACT trial is a two-armed , parallel-group , multicentre RCT to assess the efficacy of PACT in comparison with usual physiotherapy care ( UC ) . 240 patients referred to physiotherapy with CLBP will be recruited from three National Health Service ( NHS ) hospitals trusts . Inclusion criteria are : age ≥18 years , CLBP ≥12-week duration , scoring ≥3 points on the Rol and -Morris Disability Question naire ( RMDQ ) and adequate underst and ing of spoken and written English to participate . Patients will be r and omised to PACT or UC ( 120 per arm stratified by centre ) by an independent r and omisation service and followed up at 3 and 12 months post r and omisation . The sample size of 240 will provide adequate power to detect a st and ardised mean difference of 0.40 in the primary outcome ( RMDQ ; 5 % significance , 80 % power ) assuming attrition of 20 % . Analysis will be by intention to treat conducted by the trial statistician , blind to treatment group , following a prespecified analysis plan . Estimates of treatment effect at the follow-up assessment s will use an intention-to-treat framework , implemented using a linear mixed-effects model . Ethics and dissemination This trial has full ethical approval ( 14/SC/0277 ) . It will be disseminated via peer- review ed publications and conference presentations . The results will enable clinicians , patients and health service managers to make informed decisions regarding the efficacy of PACT for patients with CLBP . Trial registration number IS RCT N95392287 ; Pre- results Summary Background Back pain remains a challenge for primary care internationally . One model that has not been tested is stratification of the management according to the patient 's prognosis ( low , medium , or high risk ) . We compared the clinical effectiveness and cost-effectiveness of stratified primary care ( intervention ) with non-stratified current best practice ( control ) . Methods 1573 adults ( aged ≥18 years ) with back pain ( with or without radiculopathy ) consultations at ten general practice s in Engl and responded to invitations to attend an assessment clinic . Eligible participants were r and omly assigned by use of computer-generated stratified blocks with a 2:1 ratio to intervention or control group . Primary outcome was the effect of treatment on the Rol and Morris Disability Question naire ( RMDQ ) score at 12 months . In the economic evaluation , we focused on estimating incremental quality -adjusted life years ( QALYs ) and health-care costs related to back pain . Analysis was by intention to treat . This study is registered , number IS RCT N37113406 . Findings 851 patients were assigned to the intervention ( n=568 ) and control groups ( n=283 ) . Overall , adjusted mean changes in RMDQ scores were significantly higher in the intervention group than in the control group at 4 months ( 4·7 [ SD 5·9 ] vs 3·0 [ 5·9 ] , between-group difference 1·81 [ 95 % CI 1·06–2·57 ] ) and at 12 months ( 4·3 [ 6·4 ] vs 3·3 [ 6·2 ] , 1·06 [ 0·25–1·86 ] ) , equating to effect sizes of 0·32 ( 0·19–0·45 ) and 0·19 ( 0·04–0·33 ) , respectively . At 12 months , stratified care was associated with a mean increase in generic health benefit ( 0·039 additional QALYs ) and cost savings ( £ 240·01 vs £ 274·40 ) compared with the control group . Interpretation The results show that a stratified approach , by use of prognostic screening with matched pathways , will have important implication s for the future management of back pain in primary care . Funding Arthritis Research UK Treating mental disorders is a critical issue for modern societies due to high costs for the different national healthcare systems . Evidence -based psychological therapies and structured psychotherapies have been recommended for common mental health problems , but real provision of them has not yet achieved significant spread and impact ( Mukuria et al. , 2013 ) . To improve access to psychological therapies may provide cost-effective solutions , since their positive long-term impact on health has been largely demonstrated ( Castelnuovo , 2010a , b ; Campbell et al. , 2013 ; Dezetter et al. , 2013 ; Mukuria et al. , 2013 ; Emmelkamp et al. , 2014 ) . However , in many developed countries , such as France or Italy , psychotherapies are not enough covered and promoted by the national healthcare systems and health insurance companies ( Dezetter et al. , 2013 ) . Differently , in the UK , to tackle the huge problem of mental illness , a comprehensive programme of psychological therapy has been launched and watched worldwide . An estimation of its long-term clinical and economic benefits , has , in fact , led to ascertain that “ psychological therapy costs nothing ” ( Layard and Clark , 2014 ; Clark and Layard , 2015 ) . In order to mimic the positive experience developed in the UK , other countries have now to demonstrate not only the fundamental role and scientific validity of psychological treatments in both clinical and health setting s , but also their significant cost-efficacy . As noted by Emmelkamp et al. ( 2014 ) , “ There is little doubt from a scientific perspective that psychotherapy according to this definition is effective , highly beneficial and cost-effective for a wide range of mental disorders and health conditions , such as anxiety , stress and trauma-related disorders , depressive and somatoform and pain disorders , personality disorder , substance use disorders and behavioral addictions , eating disorders and a number of childhood disorders . For all these disorders , various variants of CBT have been established in clinical r and omized trials ” ( pp . 66 , 67 ) , but research in psychotherapy lacks of cost-benefit analysis of interventions : “ even if a psychological treatment could show strong efficacy and /or effectiveness , due to high costs it might never be assimilated in real clinical practice ” ( p. 67 , Emmelkamp et al. , 2014 ) . Unfortunately , most clinical psychologists and psychotherapists are not willing to measure the impact of their clinical practice , even if Beutler ( 2009 ) underlined that the gap existing between science and practice could be more imputed to scientists ' attitude than to practitioners ' intransigence : “ scientists were intentionally obscuring many important results because of an unwarranted devotion to a limited number of scientific methods . In fact , I came to believe that they may be using methods and defining psychotherapy and research informed practice in ways that hindered clinicians from being optimally effective ” ( p. 301 , Beutler , 2009 ) . Considering that psychological therapies should be studied not only in the narrow frame of Empirically Supported Treatments ( ESTs ) approach , but also using different and integrated research and statistical methods ( Beutler , 2009 ) , their cost-effectiveness demonstration remains an unaddressed issue in the psychotherapy field . Indeed , as argued by Lilienfeld et al. ( 2013 ) with references to how to promote new evidence -based psychological treatments , “ organizational support is often tied to the perceived financial viability of a new treatment ( Nelson et al. , 2006 ) . Consequently , in order to obtain financial support for learning new approaches and techniques within a clinical context , professionals must first estimate and prove the economic gain of training courses to funding organizations . Treatments that have not demonstrated ( or treatments whose cost-effectiveness have not been explored ) are therefore less viable options for organizations to support ” ( p. 895 , Lilienfeld et al. , 2013 ) . More clinical studies aim ed at providing cost-offset estimations also measuring additional intangible benefits and showing that psychological treatments could be effective , at both clinical and economic levels , are thus necessary ( Wunsch et al. , 2014 ) . It is important not to confuse a necessary cost-effective approaches in psychotherapy with dangerous cheap performances provided by the mental health practitioners : “ while cost-effective treatments can yield savings in healthcare costs , disability cl aims , and other societal costs , cost-effective by no means translates to cheap but instead describes treatments that are clinical ly effective and provided at a cost that is considered reasonable given the benefit they provide , even if the treatments increase direct expenses ” ( p. 423 , Lazar , 2014 ) . In clinical psychology , st and ardized , and internationally recognized psychotherapeutic outcome measures have therefore been developed in order to demonstrate patient improvements ( Tarescavage and Ben-Porath , 2014 ) , and an ample set of measurements that are useful to evaluate patients outcomes is currently available considering different criteria ( administration time and cost , psychometrics and sensitivity to change , etc . ) . Among these , the Behavior and Symptom Identification Scale-24 ( BASIS-24 ) ; the Clinical Outcomes in Routine Evaluation Outcome Measure ( CORE-OM ) ; the Depression Anxiety Stress Scales ( DASS ) ; the Health Survey Short Form-36 ( SF-36 ) ; the Outcome Question naire-45 ( OQ-45 ) ; the Patient Reported Outcome Measurement Information System ( PROMIS ) ; the Symptom Checklist-90-Revised ( SCL-90-R ) ; and the Brief Symptom Inventory ( BSI ) ( Tarescavage and Ben-Porath , 2014 ) are just a few . However , no agreement has been yet reached over what constitutes relevant ad universal measurements in psychopathology , as requested by the International Consortium for Health Outcomes Measurement ( ICHOM ) ( Porter et al. , 2016 ) . Also , clinical psychologists and research ers should strive to develop st and ardized sets of measures able to estimate savings costs of psychological treatments . In this regard , commonly used analytic approaches to obtain economic evaluations of health care services are : ( 1 ) cost-benefit analysis ( focusing on the socially desirable outcome achieved by a particular treatment ) , ( 2 ) cost-effectiveness analysis ( taking into account the relationship between monetary costs and measures of treatment outcome , evaluating a possible symptoms reduction or a growing work productivity ) , ( 3 ) cost-utility analysis ( with similar features of the cost-effectiveness analysis but using a valuing metric for measuring the treatment impact st and ardized in terms of quality -adjusted life years — QALY ) . Considering not only the clinical efficacy of ESTs , but also the number of years of life in which an individual would be expected to be completely free of symptoms or disability is a key point to persuade policy makers and administrators that allocation of re sources to psychological interventions would lead to both clinical and economic advantages ( Hunsley , 2002 ) . Taking into account that the future of the health care systems will be the promising stepped care approach for both chronic care pathologies ( Davison , 2000 ; Richards et al. , 2003 , 2012 ; Hermens et al. , 2014 ; Castelnuovo et al. , 2015a , b ; Delgadillo et al. , 2015 ) and mental disorders ( Richards , 2012 ; Watzke et al. , 2014 ; Gidding et al. , 2015 ; Gureje et al. , 2015 ; Haug et al. , 2015 ; Manber et al. , 2015 ; Oladeji et al. , 2015 ; Palmer et al. , 2015 ; Paris , 2015 ; Salloum et al. , 2015 ; Edelman et al. , 2016 ) , clinical psychologists will play a key role in delivering positive outcomes by continuously revising and progressively intensifying the therapeutic process through the reduction of costs . Despite evidence of the efficacy and effectiveness of the stepped care approach in the clinical field has not been yet reached , positive results have been obtained for preventive treatments aim ed at reducing subthreshold depression , which used Internet for individuals who were not able to take part in group interventions ( Munoz et al. , 1995 ; Willemse et al. , 2004 ; Van't Veer-Tazelaar et al. , 2009 ; Cuijpers et al. , 2010 ) . Instead , another recent study ( Van Beljouw et al. , 2015 ) evaluating an outreaching stepped care program on depressive symptoms in older adults failed to demonstrate the utility of the model , while revealing a single ( and not stepped ) treatment chosen by the participants being sufficient to achieve positive clinical outcomes . Still , further evidence of the cost-benefit , cost-effectiveness , and cost-utility of both single and stepped care approaches in clinical psychology are needed . Useful indications suggesting how to legitimize clinical psychology in health care system are provided in Table Table11 . Table 1 Steps to legitimize clinical psychology in health care system . Future research in psychology and psychotherapy should , therefore , focus more on cost-effective solutions for the treatment of mental disorders , also considering opportunities provided by new technologies ( Castelnuovo et al. , 2003 , 2014 ; Cartreine et al. , 2010 ; Castelnuovo and Simpson , 2011 ; And rews and Williams , 2014 ) The purpose of this r and omized noninferiority trial was to compare video teleconferencing ( VTC ) versus in-person ( IP ) delivery of an 8-week acceptance and commitment therapy ( ACT ) intervention among veterans with chronic pain ( N = 128 ) at post-treatment and at 6-month follow-up . The primary outcome was the pain interference subscale of the Brief Pain Inventory . Secondary outcomes included measures of pain severity , mental and physical health-related quality of life , pain acceptance , activity level , depression , pain-related anxiety , and sleep quality . In intent to treat analyses using mixed linear effects modeling , both groups exhibited significant improvements on primary and secondary outcomes , with the exception of sleep quality . Further , improvements in activity level at 6-month follow-up were significantly greater in the IP group . The noninferiority hypothesis was supported for the primary outcome and several secondary outcomes . Treatment satisfaction was similar between groups ; however , significantly more participants withdrew during treatment in the VTC group compared with the IP group , which was moderated by activity level at baseline . These findings generally suggest that ACT delivered via VTC can be as effective and acceptable as IP delivery for chronic pain . Future studies should examine the optimal delivery of ACT for patients with chronic pain who report low levels of activity . This trial was registered at Clinical Trials.gov ( NCT01055639 ) . PERSPECTIVE This study suggests that ACT for chronic pain can be implemented via VTC with reductions in pain interference comparable with IP delivery . This article contains potentially important information for clinicians using telehealth technology to deliver psychosocial interventions to individuals with chronic pain Interdisciplinary pain management programs have an established record of significantly improving the functioning of persons disabled with chronic pain . There is a group of pain sufferers , however , who have difficulty accessing these programs and for whom the effectiveness of these treatments in unknown , these are patients whose mobility and self‐care deficits leave them unable to meet the practical dem and s of many treatment environments . The purpose of this study was to examine the results of a treatment program design ed to meet the needs of these highly disabled individuals ( n=53 ) in comparison to results obtained from a st and ard less‐disabled group attending treatment at the same facility ( n=234 ) . Results from the highly disabled patients showed statistically significant change after treatment in eight of nine outcome variables , including improvements in pain‐related distress , disability , depression , pain‐related anxiety , daytime rest , and performance during an activity tolerance test . Effect size calculations showed a number of large treatment effects , for psychosocial disability , depression , and acceptance of pain . Analysis of reliable change and clinical significance demonstrated that results were not merely statistically significant but clinical ly meaningful . Results appeared stable at three months following treatment . This research plays an important part in establishing an evidence base to inform service development , ensuring that chronic pain services do not exclude people on the basis of the severity of their disability BACKGROUND Psychological flexibility theory ( PFT ) suggests three key processes of change : increases in value-directed behaviors , reduction in struggle with symptoms , and reduction in suffering . We hypothesized that Acceptance and Commitment Therapy ( ACT ) would change these processes and that increases in valued action and decreases in struggle would precede change in suffering . METHOD Data were derived from a r and omized clinical trial testing ACT ( vs. waitlist ) for treatment-resistant patients with primary panic disorder with/without agoraphobia ( n = 41 ) . Valued behavior , struggle , and suffering were assessed at each of eight sessions . RESULTS Valued actions , struggle , and suffering all changed over the course of therapy . Overall changes in struggle and suffering were interdependent whereas changes in valued behavior were largely independent . Levels of valued behaviors influenced subsequent suffering , but the other two variables did not influence subsequent levels of valued action . DISCUSSION This finding supports a central tenet of PFT that increased (re-)engagement in valued behaviors precedes reductions in suffering . Possible implication s for a better underst and ing of response and non-response to psychotherapy are discussed Acceptance and commitment therapy ( ACT ) is a developing approach for chronic pain . The current study was design ed to pilot test a brief , widely inclusive , local access format of ACT in a UK primary care setting . Seventy-three participants ( 68.5 % women ) were r and omized to either ACT or treatment as usual ( TAU ) . Many of the participants were aged 65 years or older ( 27.6 % ) , were diagnosed with fibromyalgia ( 30.2 % ) and depression ( 40.3 % ) , and had longst and ing pain ( median = 10 years ) . St and ard clinical outcome measures included disability , depression , physical functioning , emotional functioning , and rated improvement . Process measures included pain-related and general psychological acceptance . The recruitment target was met within 6 months , and 72.9 % of those allocated to ACT completed treatment . Immediately post treatment , relative to TAU , participants in ACT demonstrated lower depression and higher ratings of overall improvement . At a 3-month follow-up , again relative to TAU , those in ACT demonstrated lower disability , less depression , and significantly higher pain acceptance ; d = .58 , .59 , and .64 , respectively . Analyses based on intention-to-treat and on treatment “ completers , ” perhaps predictably , revealed more sobering and more encouraging results , respectively . A larger trial of ACT delivered in primary care , in the format employed here , appears feasible with some recommended adjustments in the methods used here ( Trial registration : IS RCT N49827391 ) . Perspective This article presents a pilot r and omized controlled trial of ACT for chronic pain in a primary care setting in the United Kingdom . Both positive clinical outcomes and ways to improve future trials are reported |
12,190 | 30,617,161 | Shorter 6MWD and elevated fibrinogen and CRP were associated with exacerbation , and shorter 6MWD , higher heart rate , CRP and IL-6 were associated with hospitalisation .
Few studies examined associations with musculoskeletal measures .
Conclusion Findings suggest 6MWD , heart rate , CRP , fibrinogen and WCC are associated with clinical outcomes in patients with stable COPD . | Background Conventional measures to evaluate COPD may fail to capture systemic problems , particularly musculoskeletal weakness and cardiovascular disease .
Identifying these manifestations and assessing their association with clinical outcomes ( ie , mortality , exacerbation and COPD hospital admission ) is of increasing clinical importance .
Objective To assess associations between 6 min walk distance ( 6MWD ) , heart rate , fibrinogen , C reactive protein ( CRP ) , white cell count ( WCC ) , interleukins 6 and 8 ( IL-6 and IL-8 ) , tumour necrosis factor-alpha , quadriceps maximum voluntary contraction , sniff nasal inspiratory pressure , short physical performance battery , pulse wave velocity , carotid intima-media thickness and augmentation index and clinical outcomes in patients with stable COPD . | Background : TORCH ( Towards a Revolution in COPD Health ) is an international multicentre , r and omised , placebo-controlled clinical trial of inhaled fluticasone propionate/salmeterol combination treatment and its monotherapy components for maintenance treatment of moderately to severely impaired patients with chronic obstructive pulmonary disease ( COPD ) . The primary outcome is all-cause mortality . Cause-specific mortality and deaths related to COPD are additional outcome measures , but systematic methods for ascertainment of these outcomes have not previously been described . Methods : A Clinical Endpoint Committee ( CEC ) was tasked with categorising the cause of death and the relationship of deaths to COPD in a systematic , unbiased and independent manner . The key elements of the operation of the committee were the use of predefined principles of operation and definitions of cause of death and COPD -relatedness ; the independent review of cases by all members with development of a consensus opinion ; and a substantial infrastructure to collect medical information . Results : 911 deaths were review ed and consensus was reached in all . Cause-specific mortality was : cardiovascular 27 % , respiratory 35 % , cancer 21 % , other 10 % and unknown 8 % . 40 % of deaths were definitely or probably related to COPD . Adjudications were identical in 83 % of blindly re-adjudicated cases ( κ = 0.80 ) . COPD -relatedness was reproduced 84 % of the time ( κ = 0.73 ) . The CEC adjudication was equivalent to the primary cause of death recorded by the site investigator in 52 % of cases . Conclusion : A CEC can provide st and ardised , reliable and informative adjudication of COPD mortality that provides information which frequently differs from data collected from assessment by site investigators Background It is unclear whether elevated plasma C reactive protein ( CRP ) is causally related to chronic obstructive pulmonary disease ( COPD ) . The authors tested the hypothesis that genetically elevated plasma CRP causes COPD using a Mendelian r and omisation design . Methods The authors measured high-sensitivity CRP in plasma , genotyped for four single nucleotide polymorphisms in the CRP gene , and screened for spirometry-defined COPD and hospitalisation due to COPD in 7974 individuals from the Copenhagen City Heart Study and in 32 652 individuals from the Copenhagen General Population Study . Results Elevated plasma CRP > 3 mg/l compared with < 1 mg/l was associated with risk estimates of 1.8 and 2.8 for spirometry-based COPD and of 1.6 and 1.8 for hospitalisation due to COPD in the Copenhagen City Heart Study and the Copenhagen General Population Study , respectively . Genotype combinations of the four CRP polymorphisms were associated with up to a 62 % increase in plasma CRP . However , these genotype combinations did not associate with increased risk of COPD or hospitalisation due to COPD in either cohort or in the two cohorts combined . On instrumental variable analysis , a doubling of plasma CRP versus a doubling of genetically elevated CRP result ed in ORs for COPD of 1.27 ( 95 % CI 1.25 to 1.30 ) versus 1.01 ( 0.81 to 1.26 ) and for COPD hospitalisation of 1.47 ( 1.43 to 1.51 ) versus 0.82(0.59 to 1.13 ) . Conclusion Although elevated CRP is related to both a diagnosis of COPD and subsequent hospital admission , genetically elevated plasma CRP is not associated with an increased risk of clinical COPD . This suggests that the association between CRP levels and COPD is not causal Rationale : Chronic obstructive pulmonary disease ( COPD ) is associated with a 2–3-fold increase in the risk of ischaemic heart disease , stroke and sudden death . The mechanisms responsible for this association are not clear and appear to be independent of smoking history . Objective : We test the hypothesis that patients with COPD have increased arterial stiffness and blood pressure in comparison with age and smoking matched controls . Methods : In a prospect i ve case control study , we recruited 102 patients with COPD and 103 healthy controls matched for age and smoking status . Patients were assessed by clinical history and spirometry , with arterial stiffness and blood pressure determined using radial artery applanation tonometry and sphygmomanometry . Results : Patients with COPD had increased arterial stiffness compared with matched controls , with elevated augmentation pressure ( 17 ( 1 ) vs 14 ( 1 ) mm Hg ; p = 0.005 ) and a reduced time to wave reflection ( 131 ( 1 ) vs 137 ( 2 ) ms ; p = 0.004 ) . These differences were associated with increases in both diastolic ( 82 ( 1 ) vs 78 ( 1 ) mm Hg ; p = 0.005 ) and systolic blood pressure ( 147 ( 2 ) vs 132 ( 2 ) mm Hg ; p<0.001 ) . Serum C reactive protein concentrations were threefold higher in patients ( 6.1 ( 0.9 ) vs 2.3 ( 0.4 ) mg/l ; p = 0.001 ) . Data are presented as mean ( SEM ) . Conclusions : Patients with COPD have increased arterial stiffness and blood pressure in comparison with controls matched for age and smoking status . We speculate that increased systemic inflammation and vascular dysfunction could potentially explain the excess cardiovascular morbidity and mortality associated with COPD Background Health-related quality of life ( HRQL ) is considered as an important outcome parameter in patients with chronic diseases . This study aim ed to assess the role of disease-specific HRQL for long-term survival in patients of different diagnoses with chronic hypercapnic respiratory failure ( CHRF ) . Methods In a cohort of 231 stable patients ( chronic obstructive pulmonary disease ( COPD ) , n = 98 ; non- COPD ( obesity-hypoventilation syndrome , restrictive disorders , neuromuscular disorders ) , n = 133 ) with CHRF and current home mechanical ventilation ( HMV ) , HRQL was assessed by the disease-specific Severe Respiratory Insufficiency ( SRI ) question naire and its prognostic value was prospect ively evaluated during a follow-up of 2–4 years , using univariate and multivariate regression analysis . Results HRQL was more impaired in COPD ( mean ± SD SRI- summary score ( SRI-SS ) 52.5 ± 15.6 ) than non- COPD patients ( 67.6 ± 16.4 ; p < 0.001 ) . Overall mortality during 28.9 ± 8.8 months of follow-up was 19.1 % ( 31.6 % in COPD , 9.8 % in non- COPD ) . To identify the overall role of SRI , we first evaluated the total study population . SRI-SS and its subdomains ( except attendance symptoms and sleep ) , as well as body mass index ( BMI ) , leukocyte number and spirometric indices were associated with long-term survival ( p < 0.01 each ) . Of these , SRI-SS , leukocytes and forced expiratory volume in 1 s ( FEV1 ) turned out to be independent predictors ( p < 0.05 each ) . More specifically , in non- COPD patients SRI-SS and most of its subdomains , as well as leukocyte number , were related to survival ( p < 0.05 ) , whereas in patients with COPD only BMI and lung function but not SRI were predictive . Conclusion In patients with CHRF and HMV , the disease-specific SRI was an overall predictor of long-term survival in addition to established risk factors . However , the SRI predominantly beared information regarding long-term survival in non- COPD patients , while in COPD patients objective measures of the disease state were superior . This on one h and highlights the significance of HRQL in the long-term course of patients with CHRF , on the other h and it suggests that the predictive value of HRQL depends on the underlying disease Background In addition to smoking , acute exacerbations are considered to be a contributing factor to progression of chronic obstructive pulmonary disease ( COPD ) . However , these findings come from studies including active smokers , while results in ex-smokers are scarce and contradictory . The purpose of this study was to evaluate if frequent acute moderate exacerbations are associated with an accelerated decline in forced expiratory volume in one second ( FEV1 ) and impairment of functional and clinical outcomes in ex-smoking COPD patients . Methods A cohort of 100 ex-smoking patients recruited for a 2-year follow-up study was evaluated at inclusion and at 6-monthly scheduled visits while in a stable condition . Evaluation included anthropometry , spirometry , inspiratory capacity , peripheral capillary oxygen saturation , severity of dyspnea , a 6-minute walking test , BODE ( Body mass index , airflow Obstruction , Dyspnea , Exercise performance ) index , and quality of life ( St George ’s Respiratory Question naire and Chronic Respiratory Disease Question naire ) . Severity of exacerbation was grade d as moderate or severe according to health care utilization . Patients were classified as infrequent exacerbators if they had no or one acute exacerbation/year and frequent exacerbators if they had two or more acute exacerbations/year . R and om effects modeling , within hierarchical linear modeling , was used for analysis . Results During follow-up , 419 ( 96 % moderate ) acute exacerbations were registered . At baseline , frequent exacerbators had more severe disease than infrequent exacerbators according to their FEV1 and BODE index , and also showed greater impairment in inspiratory capacity , forced vital capacity , peripheral capillary oxygen saturation , 6-minute walking test , and quality of life . However , no significant difference in FEV1 decline over time was found between the two groups ( 54.7±13 mL/year versus 85.4±15.9 mL/year in frequent exacerbators and infrequent exacerbators , respectively ) . This was also the case for all other measurements . Conclusion Our results suggest that frequent moderate exacerbations do not contribute to accelerated clinical and functional decline in COPD patients who are ex-smokers Background Although it is known that patients with chronic obstructive pulmonary disease ( COPD ) generally do have an increased heart rate , the effects on both mortality and non-fatal pulmonary complications are unclear . We assessed whether heart rate is associated with all-cause mortality , and non-fatal pulmonary endpoints . Methods A prospect i ve cohort study of 405 elderly patients with COPD was performed . All patients underwent extensive investigations , including electrocardiography . Follow-up data on mortality were obtained by linking the cohort to the Dutch National Cause of Death Register and information on complications ( exacerbation of COPD or pneumonia ) by scrutinizing patient files of general practitioners . Multivariable cox regression analysis was performed . Results During the follow-up 132 ( 33 % ) patients died . The overall mortality rate was 50/1000 py ( 42–59 ) . The major causes of death were cardiovascular and respiratory . The relative risk of all-cause mortality increased with 21 % for every 10 beats/minute increase in heart rate ( adjusted HR : 1.21 [ 1.07–1.36 ] , p = 0.002 ) . The incidence of major non-fatal pulmonary events was 145/1000 py ( 120–168 ) . The risk of a non-fatal pulmonary complication increased non-significantly with 7 % for every 10 beats/minute increase in resting heart rate ( adjusted HR : 1.07 [ 0.96–1.18 ] , p = 0.208 ) . Conclusions Increased resting heart rate is a strong and independent risk factor for all-cause mortality in elderly patients with COPD . An increased resting heart rate did not result in an increased risk of exacerbations or pneumonia . This may indicate that the increased mortality risk of COPD is related to non-pulmonary causes . Future r and omized controlled trials are needed to investigate whether heart-rate lowering agents are worthwhile for COPD patients RATIONALE Accurate prediction of mortality helps select patients for interventions aim ed at improving outcome . OBJECTIVES Because chronic obstructive pulmonary disease is characterized by low- grade systemic inflammation , we hypothesized that addition of inflammatory biomarkers to established predictive factors will improve accuracy . METHODS A total of 1,843 patients enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints study were followed for 3 years . Kaplan-Meier curves , log-rank analysis , and Cox proportional hazards analyses determined the predictive value for mortality of clinical variables , while C statistics assessed the added discriminative power offered by addition of biomarkers . MEASUREMENTS AND MAIN RESULTS At recruitment we measured anthropometrics , spirometry , 6-minute walk distance , dyspnea , BODE index , history of hospitalization , comorbidities , and computed tomography scan emphysema . White blood cell and neutrophil counts , serum or plasma levels of fibrinogen , chemokine lig and 18 , surfactant protein D , C-reactive protein , Clara cell secretory protein-16 , IL-6 and -8 , and tumor necrosis factor-α were determined at recruitment and subsequent visits . A total of 168 of the 1,843 patients ( 9.1 % ) died . Nonsurvivors were older and had more severe airflow limitation , increased dyspnea , higher BODE score , more emphysema , and higher rates of comorbidities and history of hospitalizations . The best predictive model for mortality using clinical variables included age , BODE , and hospitalization history ( C statistic of 0.686 ; P < 0.001 ) . One single biomarker ( IL-6 ) significantly improved the C statistic to 0.708 , but this was further improved to 0.726 ( P = 0.003 ) by the addition of all biomarkers . CONCLUSIONS The addition of a panel of selected biomarkers improves the ability of established clinical variables to predict mortality in chronic obstructive pulmonary disease . Clinical trial registered with www . clinical trials.gov ( NCT00292552 ) Background Past studies have shown that mean values of Interleukin-6 ( IL-6 ) and C-reactive protein ( CRP ) do not change significantly in COPD patients over a one-year period . However , longer period follow-up studies are still lacking . Thus , the aim of this study is to evaluate plasma CRP and IL-6 concentration over three years in COPD patients and to test the association between these inflammatory mediators and disease outcome markers . Methods A cohort of 77 out patients with stable COPD was evaluated at baseline , and 53 ( mean FEV1 , 56 % predicted ) were included in the prospect i ve study . We evaluated Interleukin-6 ( IL-6 ) , C-reactive protein ( CRP ) , six-minute walking distance ( 6MWD ) , and body mass index ( BMI ) at baseline and after three years . Plasma concentration of IL-6 was measured by high sensitivity ELISA , and CRP was obtained by high sensitivity particle-enhanced immunonephelometry . Results IL-6 increased significantly after 3 years compared to baseline measurements [ 0.8 ( 0.5 - 1.3 ) vs 2.4 ( 1.3 - 4.4 ) pg/ml ; p < 0.001 ] and was associated with worse 6MWD performance . In the Cox regression , increased IL-6 at baseline was associated with mortality [ Hazard Ratio ( 95 % CI ) = 2.68 ( 0.13 , 1.84 ) ; p = 0.02 ] . CRP mean values did not change [ 5 ( 1.6 - 7.9 ) vs 4.7 ( 1.7 - 10 ) pg/L ; p = 0.84 ] , although eleven patients ( 21 % ) presented with changes > 3 mg/L in CRP after 3 years . Conclusions The systemic inflammatory process , evaluated by IL-6 , seems to be persistent , progressive and associated with mortality and worse physical performance in COPD patients .Trial registration Background COPD exacerbations accelerate disease progression . Aims To examine if COPD characteristics and systemic inflammatory markers predict the risk for acute COPD exacerbation ( AE COPD ) frequency and duration . Methods 403 COPD patients , GOLD stage II-IV , aged 44–76 years were included in the Bergen COPD Cohort Study in 2006/07 , and followed for 3 years . Examined baseline predictors were sex , age , body composition , smoking , AE COPD the last year , GOLD stage , Charlson comorbidity score ( CCS ) , hypoxemia ( PaO2<8 kPa ) , cough , use of inhaled steroids , and the inflammatory markers leucocytes , C-reactive protein ( CRP ) , neutrophil gelatinase associated lipocalin ( NGAL ) , soluble tumor necrosis factor receptor 1 ( sTNF-R1 ) , and osteoprotegrin ( OPG ) . Negative binomial models with r and om effects were fitted to estimate the annual incidence rate ratios ( IRR ) . For analysis of AE COPD duration , a generalized estimation equation logistic regression model was fitted , also adjusting for season , time since inclusion and AE COPD severity . Results After multivariate adjustment , significant predictors of AE COPD were : female sex [ IRR 1.45 ( 1.14–1.84 ) ] , age per 10 year increase [ 1.23 ( 1.03–1.47 ) ] , > 1 AE COPD last year before baseline [ 1.65 ( 1.24–2.21 ) ] , GOLD III [ 1.36 ( 1.07–1.74 ) ] , GOLD IV [ 2.90 ( 1.98–4.25 ) ] , chronic cough [ 1.64 ( 1.30–2.06 ) ] and use of inhaled steroids [ 1.57 ( 1.21–2.05 ) ] . For AE COPD duration more than three weeks , significant predictors after adjustment were : hypoxemia [ 0.60 ( 0.39–0.92 ) ] , years since inclusion [ 1.19 ( 1.03–1.37 ) ] , AE COPD severity ; moderate [ OR 1.58 ( 1.14–2.18 ) ] and severe [ 2.34 ( 1.58–3.49 ) ] , season ; winter [ 1.51 ( 1.08–2.12 ) ] , spring [ 1.45 ( 1.02–2.05 ) ] and sTNF-R1 per SD increase [ 1.16 ( 1.00–1.35 ) ] . Conclusion Several COPD characteristics were independent predictors of both AE COPD frequency and duration Background Chronic obstructive pulmonary disease ( COPD ) typically presents the characteristic clinical condition of exacerbation , with more intense symptoms associated with greater functional loss and consequently lower chances of patient survival . Objectives This study sought to determine the predictors of exacerbation , alone or in combination , in patients with chronic obstructive pulmonary disease ( COPD ) who received physical therapeutic treatment over 6 months . Method This was an observational , longitudinal and prospect i ve study in which 63 COPD patients residing within the municipality of São Carlos , SP , Brazil were evaluated . These patients had COPD stages II and III and were entered into a physical therapy program , consisting of 3 periods of assessment over 6 months . We evaluated the occurrence of acute exacerbation as well as the patients ' body mass index ( BMI ) , fat-free mass ( FFM ) , fat-free mass index , forced expiratory volume in 1 second ( FEV1 ) , dyspnea , distance walked ( DW ) in the 6-minute walk test ( 6MWT ) and h and grip strength . Results When applying Cox setting s with each covariate separately , the results revealed 5 % significance only for the DW in the 6MWT , which demonstrated an interaction between BMI and FFM . Comparison of the 3 periods of assessment across the covariates measured showed a significant difference only for the DW between evaluations in the 3rd and 6th months . Conclusion Upon analyzing the predictors of risk over 6 months of follow-up in patients with COPD , we found that the DW in the 6MWT was associated with the risk of exacerbation , although this risk also depended on the covariates BMI and FFM The clinical significance of high heart rate in chronic obstructive pulmonary disease ( COPD ) is unexplored . We investigated the association between resting heart rate , pulmonary function , and prognosis in subjects with COPD . 16 696 subjects aged ≥40 years from the Copenhagen City Heart Study , a prospect i ve study of the general population , were followed for 35.3 years , 10 986 deaths occurred . Analyses were performed using time-dependent Cox-models and net reclassification index ( NRI ) . Resting heart rate increased with severity of COPD ( p<0.001 ) . Resting heart rate was associated with both cardiovascular and all-cause mortality across all stages of COPD ( p<0.001 ) . Within each stage of COPD , resting heart rate improved prediction of median life expectancy ; the difference between < 65 bpm and > 85 bpm was 5.5 years without COPD , 9.8 years in mild ( Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) stage I ) , 6.7 years in moderate ( GOLD stage II ) and 5.9 years in severe/very severe COPD ( GOLD stage III/IV ) , ( p<0.001 ) . Resting heart rate significantly improved risk prediction when added to GOLD stage ( categorical NRI 4.9 % , p = 0.01 ; category less NRI 23.0 % , p<0.0001 ) or forced expiratory volume in 1 s % predicted ( categorical NRI 7.8 % , p = 0.002 ; category less NRI 24.1 % , p<0.0001 ) . Resting heart rate increases with severity of COPD . Resting heart rate is a readily available clinical variable that improves risk prediction in patients with COPD above and beyond that of pulmonary function alone . Resting heart rate may be a potential target for intervention in COPD Exercise impairment as measured by the 6-min walk distance ( 6MWD ) test afflicts many patients with chronic obstructive pulmonary disease ( COPD ) and is known to predict mortality . Reference equations for the 6MWD in adults have been published but not yet vali date d. The present authors prospect ively followed 1,379 COPD patients for 55±30 months and tested the predictive value of the baseline 6MWD in metres , the 6MWD work ( kg·m−1 ) and as a percentage of predicted values the 6MWD in meters according to two reference equations . All-cause mortality was the validating outcome . The best threshold values were identified for each of the tests using receiver operating characteristic ( ROC ) curves . The threshold values obtained were : 350 m for the 6MWD , 25,000 kg·m−1 for the 6MWD work , and 67 and 54 % predicted for the two reference equations . All modalities of the testing were similar at predicting COPD mortality and correlated well with the 6MWD test . In conclusion , all modalities of testing predict mortality in chronic obstructive pulmonary disease equally well . In the 6-min walk distance test , a value < 350 m is associated with increased mortality and should be regarded as abnormal BACKGROUND Frequent exacerbations are associated with a faster decline in FEV(1 ) , impaired health status , and worse survival . Their impact and temporal relationship with other outcomes such as functional status , dyspnea , and the multidimensional body mass index , obstruction , dyspnea , exercise capacity ( BODE ) index remain unknown . HYPOTHESIS We reasoned that exacerbations affect the BODE index and its components , and that changes in the BODE index could be used to monitor the effect of exacerbations on the host . STUDY DESIGN Prospect i ve observational study in a Veterans Affairs medical center . METHODS We studied 205 patients with COPD ( mean [ + /- SD ] FEV(1 ) , 43 + /- 15 % predicted ) , and recorded the body mass index , FEV(1 ) percent predicted , modified Medical Research Council dyspnea scale , 6-min walk distance , and the BODE index at baseline , during the exacerbation , and at 6 , 12 , and 24 months following the first episode , and documented all exacerbations for 2 years after the first acute exacerbation . RESULTS From the cohort , 130 patients ( 63 % ) experienced 352 exacerbations or ( 0.85 exacerbations per patient per year ) ; 48 patients ( 23 % ) , experienced one episode , 82 patients ( 40 % ) experienced 2 or more exacerbations , and 50 patients required hospitalization . At study entry , exacerbators had a worse mean baseline BODE index score ( 4.2 + /- 2.1 vs 3.57 + /- 2.3 , respectively ; p < 0.03 ) . The BODE index score worsened by 1.38 points during the exacerbation , and remained 0.8 and 1.1 points above baseline at 1 and 2 years , respectively . There was little change in BODE index score at 2 years in nonexacerbators . CONCLUSION COPD exacerbations negatively impact on the BODE index and its components . The BODE index is a sensitive tool used to assess the impact of exacerbations and to monitor COPD disease progression RATIONALE The 2011 combined Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) assessment incorporates symptoms , exacerbation history , and spirometry in discriminating risk of exacerbations in patients with chronic obstructive pulmonary disease ( COPD ) . Six-minute-walk distance ( 6MWD ) and accelerometry also have been used to assess disease severity in COPD . The association between these measures and the risks of hospitalization and mortality in the context of GOLD 2011 is unknown . OBJECTIVES To describe changes in exercise tolerance and physical activity over time in patients with COPD and to test the hypothesis that lower baseline 6MWD or accelerometry step count is associated with increased risk of COPD -related hospitalization or all-cause mortality , independent of GOLD 2011 group . METHODS Physical function and medical outcomes were prospect ively assessed in 326 patients with moderate to severe COPD in INSPIRE-II , a r and omized controlled trial of a coping skills training intervention . Cox models were used to determine if GOLD 2011 group , 6MWD , or accelerometry steps were associated with risk of COPD -related hospitalization or all-cause mortality . MEASUREMENTS AND MAIN RESULTS Physical function declined over time in GOLD group D but remained stable in groups A , B , and C. GOLD classification was associated with time to death or first COPD -related hospitalization . Baseline 6MWD was more strongly associated with time to death or first COPD -related hospitalization ( hazard ratio , 0.50 [ 95 % confidence interval , 0.34 , 0.73 ] per 150 m , P=0.0003 ) than GOLD 2011 classification . A similar relationship was observed for accelerometry steps ( hazard ratio , 0.80 [ 95 % confidence interval , 0.70 , 0.92 ] per 1,000 steps , P=0.002 ) . CONCLUSIONS Exercise tolerance and daily physical activity are important predictors of hospitalization and mortality in COPD , independent of GOLD 2011 classification . Physical function may represent a modifiable risk factor that warrants increased attention as a target for interventions to improve clinical ly meaningful outcomes in COPD BACKGROUND Exercise tolerance is an important clinical aspect of chronic obstructive pulmonary disease that can be easily and reliably measured with the 6-minute walking test ( 6MWT ) . To improve the utility of the 6MWT for patient and health care system management , the interpretation of the functional status measure in relation to death and hospitalization should be eluci date d. METHODS Three-year , prospect i ve , multicenter observational study to evaluate the predictive power of 6MWD for death or exacerbation-related hospitalization and to evaluate the factors that help determine 6MWD . RESULTS We measured 6MWD at baseline and annually in 2110 patients with clinical ly stable Global Initiative for Obstructive Lung Disease ( GOLD ) stage II-IV COPD and recorded exacerbation-related hospitalizations and all-cause mortality . During the study , 200 patients died and 650 were hospitalized . Using receiver operating characteristics , the best predictive thresholds of the 6MWD were 334 m for increased risk of death and 357 m for exacerbation-related hospitalization ( area under the curve 0.67 and 0.60 respectively ) ; however , the discriminatory thresholds , especially for mortality , were influenced by age . The mean ( SE ) 6MWD declined by 1.6 ( 1.2 ) m per year in GOLD II , 9.8 ( 1.3 ) m per year in GOLD III , and 8.5 ( 2.4 ) m per year in GOLD IV . CONCLUSION The 6MWD provides prognostic information that may be useful for identifying high-risk patients with COPD STUDY OBJECTIVE To determine the predictive factors of morbidity and mortality in patients with end-stage respiratory disease . DESIGN Prospect i ve , multicenter cohort study . SETTING Thirteen outpatient chest clinics within the Association Nationale de Traitement à Domicile de l'Insuffisance Respiratoire . PARTICIPANTS Stable adult patients with chronic respiratory failure receiving long-term oxygen therapy and /or home mechanical ventilation ( n = 446 ; 182 women and 264 men ; aged 68.5 + /- 12.1 years [ + /- SD ] ) ; Respiratory diseases were COPD in 42.8 % , restrictive disorders in 36.3 % , mixed respiratory failure in 13.5 % , and bronchiectasis in 7.4 % . Recruitment was performed during the yearly examination . Patients with neuromuscular diseases and sleeping apnea were excluded . MEASUREMENTS AND RESULTS Hospitalization days and survival were recorded during a follow-up of 14.3 + /- 5.6 months . Body mass index ( BMI ) , serum albumin , and transthyretin levels were considered for their predictive value of outcome , together with demographic data , underlying respiratory disease , respiratory function , hemoglobin , C-reactive protein , smoking habits , oral corticosteroid use , and antibiotic treatment courses . Overall , 1.8 + /- 1.7 hospitalizations ( cumulative stay , 17.6 + /- 27.1 days ) were observed in 254 of 446 patients ( 57 % ) . Independent predictors of hospitalization were oral corticosteroids , FEV(1 ) , and plasma C-reactive protein . One-year and 2-year cumulative survivals were 93 % and 69 % , respectively . Plasma C-reactive protein , BMI , Pao(2 ) on room air , and oral corticosteroids independently predicted survival in multivariate analysis . CONCLUSION Besides established prognosis factors such as FEV(1 ) and Pao(2 ) , nutritional depletion as assessed by BMI and overall systemic inflammation as estimated by C-reactive protein appear as major determinants of hospitalization and death risks whatever the end-stage respiratory disease . BMI and C-reactive protein should be included in the monitoring of chronic respiratory failure . Oral corticosteroids as maintenance treatment in patients with end-stage respiratory disease are an independent risk factor of death , and should be avoided in most cases BACKGROUND COPD is characterized by episodic increases in respiratory symptoms , so-called exacerbations . COPD exacerbations are associated with an increase in local and systemic inflammation . Data of a previously published study in a well-characterized COPD cohort were analyzed to define predictive factors of acute exacerbations , particularly focusing on systemic inflammation . OBJECTIVE To determine if an elevated systemic inflammatory status measured at baseline is related to the occurrence of acute exacerbations in patients with COPD . METHODS The occurrence of moderate ( requiring oral prednisolone ) and severe exacerbations ( requiring hospitalization ) was prospect ively recorded over 1 year . At the beginning of the study , lung function values ( FEV1 , FVC , functional residual capacity , and diffusion capacity of the lung for carbon monoxide [ Dlco ] ) and serum levels of C-reactive protein , fibrinogen , lipopolysaccharide binding protein , tumor necrosis factor (TNF)-alpha , and its soluble receptors ( soluble TNF receptors 55 and 75 ) as markers of systemic inflammation were determined . RESULTS Two hundred seventy-seven person-years of follow-up were analyzed in the total group of 314 patients : 186 patients were responsible for 411 exacerbations ( 374 moderate and 37 severe ) . Multivariate analyses showed that a higher initial fibrinogen level and a lower FEV1 predicted a higher rate of both moderate and severe exacerbations . Additional independent predictors of a severe exacerbation were a higher number of pre study severe exacerbations and lower Dlco . A higher number of pre study moderate exacerbations was the only additional independent risk factor for the rate of moderate exacerbations . CONCLUSION This study demonstrates that besides lung function impairment systemic inflammation manifested by elevated fibrinogen levels is an independent risk factor for exacerbations of COPD . Attenuation of systemic inflammation may offer new perspectives in the management of COPD patients to reduce the burden of exacerbations BACKGROUND Identification of persons with chronic obstructive pulmonary disease ( COPD ) at risk for acute exacerbations ( AEs ) targets them for close monitoring . OBJECTIVES We examined the ability of a novel index combining physical activity and systemic inflammation to identify persons at risk for AEs . METHODS In an observational cohort study of 167 persons with COPD , we assessed daily step count , a direct measure of physical activity , with the StepWatch Activity Monitor and measured plasma C-reactive protein ( CRP ) and IL-6 levels . AEs and COPD -related hospitalizations were assessed prospect ively over a median of 16 months . Predictors of AEs and COPD -related hospitalizations were assessed using negative binomial models . MEASUREMENTS AND MAIN RESULTS Median daily step count was 5,203 steps ( interquartile range , 3,627 - 7,024 ) . Subjects with daily step count ≤ 5,203 and CRP > 3 mg/l had an increased rate of AEs ( rate ratio [ RR ] , 2.06 ; 95 % confidence interval [ CI ] , 1.30 - 3.27 ) and COPD -related hospitalizations ( RR , 3.51 ; 95 % CI , 1.73 - 7.11 ) compared with subjects with daily step count > 5,203 and CRP ≤ 3 mg/l , adjusting for FEV1 % predicted and prednisone use for AE in the previous year . Similarly , subjects with daily step count ≤ 5,203 and IL-6 > 2 pg/ml had an increased rate of AEs ( RR , 2.04 ; 95 % CI , 1.14 - 3.63 ) and COPD -related hospitalizations ( RR , 4.27 ; 95 % CI , 1.56 - 11.7 ) compared with subjects with daily step count > 5,203 and IL-6 ≤ 2 pg/ml . CONCLUSIONS An index combining daily step count and systemic inflammation can predict AEs and COPD -related hospitalizations . A validation study in a separate cohort is needed to confirm the utility of the proposed index as a clinical tool to risk stratify persons with COPD BACKGROUND Cognitive impairment frequently occurs in elderly COPD patients , but little is known about its prognostic implication s. We aim ed at evaluating the prognostic role of cognitive impairment in patients with severe COPD . METHODS Our series consisted of 149 stable patients ( mean [ + /- SD ] age , 68.7 + /- 8.5 years ) with COPD and a Pao(2 ) of < 57 mm Hg at rest ( n = 97 ) or at the end of the 6-min walking test ( n = 37 ) who were enrolled in a prospect i ve observational study . After a multidimensional baseline assessment , patients were followed up by telephone calls for a mean duration of 32.5 + /- 9.2 months ( minimal follow-up duration , 24 months ) ; 134 patients were successfully tracked . We used multivariable Cox proportional hazard analysis to identify predictors of death among clinical /functional variables that previously were shown to have prognostic implication s and among neuropsychological indexes selected on the basis of univariate analysis . RESULTS We observed 29 deaths over a median follow-up time of 32 months . Only the two following variables were independently associated with the outcome : an abnormal score on the copy with l and mark test ( hazard ratio [ HR ] , 2.93 ; 95 % confidence interval [ CI ] , 1.34 to 6.39 ) ; and a 6-min walk distance of < 300 m ( HR , 3.46 ; 95 % CI , 1.15 to 10.5 ) . A Pao(2 ) of < 57 mm Hg at rest ( HR , 2.19 ; 95 % CI , 0.93 to 5.18 ) and an FEV(1 ) of < 40 % predicted ( HR , 2.74 ; 95 % CI , 0.99 to 7.57 ) were nearly significantly associated with the outcome , while Paco(2 ) , body mass index , physical dependence , comorbid diseases , and the impairment of cognitive domains other than drawing impairment were unrelated to the outcome . CONCLUSIONS Drawing impairment is a risk factor for mortality and might improve the assessment of hypoxemic COPD patients Abstract Long-term outcome prediction in COPD is challenging . We conducted a prospect i ve 5–7-year follow-up study in patients with COPD to determine the association of exacerbation type , discharge levels of inflammatory biomarkers including procalctionin ( PCT ) , C-reactive protein ( CRP ) , white blood cell count ( WBC ) and plasma proadrenomedullin ( ProADM ) , alone or combined with demographic/ clinical characteristics , with long-term all-cause mortality in the COPD setting . The analyzed cohort comprised 469 patients with index hospitalization for pneumonic ( n = 252 ) or non-pneumonic ( n = 217 ) COPD exacerbation . Five-to-seven-year vital status was ascertained via structured phone interviews with patients or their household members/ primary care physicians . We investigated predictive accuracy using univariate and multivariate Cox regression models and area under the receiver operating characteristic curve ( AUC ) . After a median [ 25th–75th percentile ] 6.1 [ 5.6–6.5 ] years , mortality was 55 % ( 95%CI 50%–59 % ) . Discharge ProADM concentration was strongly associated with 5–7-year non-survival : adjusted hazard ratio (HR)/10-fold increase ( 95%CI ) 10.4 ( 6.2–17.7 ) . Weaker associations were found for PCT and no significant associations were found for CRP or WBC . Combining ProADM with demographic/ clinical variables including age , smoking status , BMI , New York Heart Association dyspnea class , exacerbation type , and comorbidities significantly improved long-term predictive accuracy over that of the demographic/ clinical model alone : AUC ( 95%CI ) 0.745 ( 0.701–0.789 ) versus 0.727 ( 0.681–0.772 ) , p = .043 . In patients hospitalized for COPD exacerbation , discharge ProADM levels appeared to accurately predict 5–7-year all-cause mortality and to improve long-term prognostic accuracy of multidimensional demographic/ clinical mortality risk assessment IMPORTANCE Exacerbations of respiratory symptoms in chronic obstructive pulmonary disease ( COPD ) have profound and long-lasting adverse effects on patients . OBJECTIVE To test the hypothesis that elevated levels of inflammatory biomarkers in individuals with stable COPD are associated with an increased risk of having exacerbations . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve cohort study examining 61,650 participants with spirometry measurements from the Copenhagen City Heart Study ( 2001 - 2003 ) and the Copenhagen General Population Study ( 2003 - 2008 ) . Of these , 6574 had COPD , defined as a ratio between forced expiratory volume in 1 second ( FEV1 ) and forced vital capacity below 0.7 . MAIN OUTCOMES AND MEASURES Baseline levels of C-reactive protein ( CRP ) and fibrinogen and leukocyte count were measured in participants at a time when they were not experiencing symptoms of exacerbations . Exacerbations were recorded and defined as short-course treatment with oral corticosteroids alone or in combination with an antibiotic or as a hospital admission due to COPD . Levels of CRP and fibrinogen and leukocyte count were defined as high or low according to cut points of 3 mg/L , 14 μmol/L , and 9 ×10(9)/L , respectively . RESULTS During follow-up , 3083 exacerbations were recorded ( mean , 0.5/participant ) . In the first year of follow-up , multivariable-adjusted odds ratios for having frequent exacerbations were 1.2 ( 95 % CI , 0.7 - 2.2 ; 17 events/1000 person-years ) for individuals with 1 high biomarker , 1.7 ( 95 % CI , 0.9 - 3.2 ; 32 events/1000 person-years ) for individuals with 2 high biomarkers , and 3.7 ( 95 % CI , 1.9 - 7.4 ; 81 events/1000 person-years ) for individuals with 3 high biomarkers compared with individuals who had no elevated biomarkers ( 9 events/1000 person-years ; trend : P = 2 × 10(-5 ) ) . Corresponding hazard ratios using maximum follow-up time were 1.4 ( 95 % CI , 1.1 - 1.8 ) , 1.6 ( 95 % CI , 1.3 - 2.2 ) , and 2.5 ( 95 % CI , 1.8 - 3.4 ) , respectively ( trend : P = 1 × 10(-8 ) ) . The addition of inflammatory biomarkers to a basic model including age , sex , FEV1 percent predicted , smoking , use of any inhaled medication , body mass index , history of previous exacerbations , and time since most recent prior exacerbation improved the C statistics from 0.71 to 0.73 ( comparison : P = 9 × 10(-5 ) ) . Relative risks were consistent in those with milder COPD , in those with no history of frequent exacerbations , and in the 2 studies separately . The highest 5-year absolute risks of having frequent exacerbations in those with 3 high biomarkers ( vs no high biomarkers ) were 62 % ( vs 24 % ) for those with Global Initiative for Chronic Obstructive Lung Disease ( GOLD ) grade s C-D ( n = 558 ) , 98 % ( vs 64 % ) in those with a history of frequent exacerbations ( n = 127 ) , and 52 % ( vs 15 % ) for those with GOLD grade s 3 - 4 ( n = 465 ) . CONCLUSIONS AND RELEVANCE Simultaneously elevated levels of CRP and fibrinogen and leukocyte count in individuals with COPD were associated with increased risk of having exacerbations , even in those with milder COPD and in those without previous exacerbations . Further investigation is needed to determine the clinical value of these biomarkers for risk stratification Background Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission . However , no tool has been vali date d to stratify patients at discharge for risk of readmission . Aim To evaluate the ability of the 4 m gait speed ( 4MGS ) , a surrogate marker of frailty , to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD ( AE COPD ) . Methods 213 patients hospitalised with an AE COPD were recruited prospect ively . 4MGS was measured on day of discharge . Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge . Results Baseline characteristics of the cohort : 52 % men ; mean age 72 years ; median FEV1 35%predicted . Mean ( SD ) 4MGS at hospital discharge was 0.61 ( 0.26 ) ms−1 . Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS ( Q4 fastest : 11.5 % ; Q3 : 20.4 % ; Q2 : 30.2 % ; Q1 slowest : 48.2 % ; ptrend<0.001 ) . Compared with Q4 , those in the slowest 4MGS quartile had unadjusted ORs ( 95 % CIs ) for 90-day readmission of 7.12 ( 2.61 to 19.44 ) for the whole cohort and 11.56 ( 3.08 to 43.35 ) in those aged 65 or over . A multivariate model incorporating 4MGS , Charlson Index , hospital admission in past year , FEV1%predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86 . Conclusions The 4MGS , a surrogate marker of physical frailty , independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD . Trial registration number NCT01507415 RATIONALE Patients with chronic obstructive pulmonary disease ( COPD ) have elevated cardiovascular risk , and myocardial injury is common during severe exacerbations . Little is known about the prevalence , magnitude , and underlying mechanisms of cardiovascular risk in community-treated exacerbations . OBJECTIVES To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury , and whether this is related to airway infection and inflammation . METHODS We prospect ively measured arterial stiffness ( aortic pulse wave velocity [ aPWV ] ) and cardiac biomarkers in 98 patients with stable COPD . Fifty-five patients had paired stable and exacerbation assessment s , repeated at Days 3 , 7 , 14 , and 35 during recovery . Airway infection was identified using polymerase chain reaction . MEASUREMENTS AND MAIN RESULTS COPD exacerbation frequency was related to stable-state arterial stiffness ( rho = 0.209 ; P = 0.040 ) . Frequent exacerbators had greater aPWV than infrequent exacerbators ( mean ± SD aPWV , 11.4 ± 2.1 vs. 10.3 ± 2.0 ms(-1 ) ; P = 0.025 ) . Arterial stiffness rose by an average of 1.2 ms(-1 ) ( 11.1 % ) from stable state to exacerbation ( n = 55 ) and fell slowly during recovery . In those with airway infection at exacerbation ( n = 24 ) this rise was greater ( 1.4 ± 1.6 vs. 0.7 ± 1.3 ms(-1 ) ; P = 0.048 ) ; prolonged ; and related to sputum IL-6 ( rho = 0.753 ; P < 0.001 ) . Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease ( n = 12 ) than those without ( n = 43 ) ( mean ± SD increase in troponin T , 0.011 ± 0.009 vs. 0.003 ± 0.006 μg/L , P = 0.003 ; N-terminal pro-brain natriuretic peptide , 38.1 ± 37.7 vs. 5.9 ± 12.3 pg/ml , P < 0.001 ) . CONCLUSIONS Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators . Arterial stiffness rises acutely during COPD exacerbations , particularly with airway infection . Increases in arterial stiffness are related to inflammation , and are slow to recover . Myocardial injury is common and clinical ly significant during COPD exacerbations , particularly in those with underlying ischemic heart disease |
12,191 | 21,901,674 | Treatment did not appear to improve functional outcome in survivors .
The only adverse effects reported were small numbers of gastrointestinal bleeds , infections and deterioration of hyperglycaemia across both groups .
There is not enough evidence to evaluate corticosteroid treatment for people with acute presumed ischaemic stroke . | BACKGROUND The majority of strokes are due to cerebral infa rct ion .
Ischaemic cerebral tissue tends to develop cytotoxic oedema which , if the blood-brain barrier is disrupted , may be followed by vasogenic oedema .
Large infa rcts can develop life-threatening massive oedema .
Early treatment with corticosteroids could theoretically help reduce both cytotoxic and vasogenic oedema and so improve the clinical outcome after a stroke .
OBJECTIVES To assess the effect of corticosteroids in acute presumed ischaemic stroke . | Fifty-four patients with acute cerebral infa rct ion were included in a double-blind study to evaluate Decadron ® as therapy . When comparison of patients with similar levels of consciousness was made , there was no significant difference between those patients receiving Decadron ® and those receiving placebo therapy . Three patients developed gastrointestinal tract bleeding in the placebo group , but there were none in the Decadron ® -treated group . There was no good correlation between the clinical state of the patient and the CSF pressure , either on admission or during the 14-day course of the study Dexamethasone and a placebo were compared as treatment for 40 patients with intracerebral hemorrhage . Of 19 patients receiving dexamethasone , 17 ( 89.5 % ) died during their hospital admission . Of 21 patients receiving a placebo , 16 ( 76.2 % ) died . The mortality rate was 100 % in 15 patients in the dexamethasone-treated group who were in coma or deep stupor on admission , and the mortality rate was 92 % in 12 patients with similar levels of consciousness who received a placebo . Several parameters of the neurological examination showed an improved quality of survival in the Decadron ® -treated group , but this was found only at certain days in the study . No overall statistically significant difference was found between the two therapies In this study with r and omized controls , we administered fludrocortisone acetate to 46 of 91 patients with subarachnoid hemorrhage in an attempt to prevent excessive natriuresis and plasma volume depletion . Fludrocortisone significantly reduced the frequency of a negative sodium balance during the first 6 days ( from 63 % to 38 % , p = 0.041 ) . A negative sodium balance was significantly correlated with decreased plasma volume during both the first 6 days ( p = 0.014 ) and during the entire 12-day study period ( p = 0.004 ) . Although fludrocortisone treatment tended to diminish the decrease in plasma volume , the difference was not significant ( p = 0.188 ) . More patients in the control group developed cerebral ischemia ( 31 % vs. 22 % ) and , consequently , more control patients were treated with plasma volume exp and ers ( 24 % vs. 15 % ) , which may have masked the effects of fludrocortisone on plasma volume . Fludrocortisone therefore reduces natriuresis and remains of possible therapeutic benefit in the prevention of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage In an open , r and omized anterospective , comparative study on encephalomalacias it was shown that with regard to the parameter of rehabilitation progress in the degree of paralysis , the patients treated with cortisone had a significantly better performance at the 5 % level . The main point of attack of cortisone appears to be in the early phase of the insult ( first 5 days ) . It seems unlikely that edema control is the only active principle . More probably this is an additional effect on cell metabolism . From these results it seems logical to continue to follow up the acute treatment of cerebral insult with cortisone and search for an optimal dosage and better confirmation A prospect i ve study of 93 acute stroke patients r and omly selected by type of antiedema treatment given ( hypertonic glicerol infusion plus dexamethasone versus dexamethasone alone ) failed to elicit any statistically significant difference between the two treatments on survival rates and quality of survival 7 and 30 days after the stroke Steroid treatment is widely used in acute cerebral infa rct ion yet its value is controversial . High dose dexamethasone ( 480 mg over 12 days ) was given in a double blind , r and omised controlled trial to 113 consecutive eligible patients with acute cerebral infa rct ion admitted to an acute stroke unit . Those with stroke for more than 48 hours , known embolic sources , diabetes , and infection were excluded . Death and quality of survival were recorded over 21 days . The active drug group ( 54 patients ) matched the placebo group ( 59 patients ) for age , initial stroke score , delay in beginning treatment , and other relevant variables . The two groups did not differ significantly in death rate or quality of survivorship . The small difference in mortality between the two groups may have represented a marginal therapeutic effect , which might reach significance in a larger sample . The widespread use of steroids in response to such a marginal therapeutic gain would expose large numbers of patients with stroke to more serious hazards of steroid treatment and convert patients who would otherwise have died into neurovegetative survivors . High dose steroid treatment was ineffective in ischaemic stroke , and the data suggest that further evaluation by a larger multicentre trial is not justified Intramuscular dexamethasone combined with intravenous low-molecular-weight dextran ( dextran 40 ) was compared with placebo in 40 patients with acute ischaemic cerebral infa rct ion . A double-blind procedure was used . Dexamethasone was given for up to 14 days and dextran 40 for up to three days after the infa rct ion . A weighted scoring system was used to evaluate neurological state and mobility . There were no differences in mortality or in improvement of the neurological or mobility scores between the two groups Fifty-three patients with acute cerebral infa rct ion were treated in a double-blind study with either dexamethasone or placebo within 24 hours of the onset of stroke . Forty-one of these survived for longer than 28 days , and the patients treated with the steroid fared slightly worse than those treated with placebo at the end of this time . Two of the five patients who died in the placebo group died of cerebral edema , compared with three out of seven patients who died in the steroid group . Infectious complications , gastrointestinal hemorrhage , and occasional serious exacerbations of diabetes occurred more commonly in the steroid group In the absence of universally accepted criteria for the medical treatment of stroke , we made a rigorously r and omized comparative study of different treatments in 300 patients . One group of patients received only a general supportive treatment design ed to ensure adequate supplies of water , electrolytes and calories , plus whatever was needed to prevent infection and correct extant associated pathology . Three other groups of patients were treated in the same way but were also given , respectively , one of the following medications : Hydergine ( S and oz ) ( a mixture of three ergot alkaloids ) , dexamethasone , and mannitol . No statistically significant difference emerged among any of the treatment groups and the reference group in terms of objective therapeutic results . The authors concluded that , at least with the dosage used in this study , none of the treatments proved more useful than conventional supportive therapy in the first 10 days after a stroke OBJECTIVE Hospital management of acute ischemic stroke varies greatly within and between different countries . This study assesses the current practice s and opinions of doctors in China routinely involved in the treatment of stroke , and compares them with those of British doctors . METHODS Question naires about the usual management of acute ischemic stroke were sent to 247 Chinese hospitals ( mostly urban ) collaborating in an acute stroke trial , seeking responses from five doctors ( one consultant , two registrars , and two house officers ) in each . After one mailing , 1,095 doctors ( 89 % ) responded . RESULTS Sixty-nine percent of the hospitals had computed tomography scanners , and 88 % of the doctors in those hospitals reported that they would routinely scan acute stroke patients ( 78 % usually within 24 hours of admission and 22 % only later ) . Sixty-two percent of doctors reported average hospital stays of 2 to 4 weeks , whereas 36 % reported longer average stays . Treatments reported to be used routinely within the first 48 hours of acute ischemic stroke included glycerol or mannitol ( 69 % of doctors ) , Chinese herb products ( 66 % ) , calcium antagonists ( 54 % ) , and aspirin ( 53 % ) ; for each of these treatments , over 70 % of all doctors believed it produced definite benefit . Reported routine use of dextran ( 44 % ) , snake venom ( 32 % ) , " photo-therapy " ( 22 % ) , and steroids ( 19 % ) was also moderately common , and about half of all doctors believed each was beneficial . In contrast , routine use of thrombolytic agents ( 4 % ) or anticoagulants ( 1 % ) was uncommon . Only one third of the doctors reported active treatment of hypertension immediately after admission . CONCLUSIONS Comparison with a similar survey in Britain showed reported use of most treatments for acute ischemic stroke was more extensive in China , but that within both countries there was wide variation . The substantial variations in clinical practice both within and between China , the United Kingdom and other countries reflect , at least in part , the substantial uncertainty about the effectiveness of many of the possible treatments for acute ischemic stroke . Large-scale r and omized evidence is needed to confirm or refute the efficacy of these and newer treatments for acute stroke The National Institute of Neurological and Communicative Disorders and Stroke initiated the Stroke Data Bank , which is a multicenter project to prospect ively collect data on the clinical course and sequelae of stroke . Additional objectives were to provide information that would enable a st and ard diagnostic clinical evaluation , to identify prognostic factors , and to provide planning data for future studies . A brief description of the structure and methods precede the baseline characterization of 1,805 patients enrolled in the Stroke Data Bank between July 1983 and June 1986 . Two thirds of these patients were admitted within 24 hours after stroke onset . Medical history , neurologic history , and hospitalization summaries are presented separately for the following stroke subtypes : infa rct ion , unknown cause ; embolism from cardiac source ; infa rct ion due to atherosclerosis ; lacune ; parenchymatous or intracerebral hemorrhage ; subarachnoid hemorrhage ; and other . The utility and limitations of these data are discussed MRC CRASH is a r and omised controlled trial ( IS RCT N74459797 ) of the effect of corticosteroids on death and disability after head injury . We r and omly allocated 10,008 adults with head injury and a Glasgow Coma Scale score of 14 or less , within 8 h of injury , to a 48-h infusion of corticosteroid ( methylprednisolone ) or placebo . Data at 6 months were obtained for 9673 ( 96.7 % ) patients . The risk of death was higher in the corticosteroid group than in the placebo group ( 1248 [ 25.7 % ] vs 1075 [ 22.3 % ] deaths ; relative risk 1.15 , 95 % CI 1.07 - 1.24 ; p=0.0001 ) , as was the risk of death or severe disability ( 1828 [ 38.1 % ] vs 1728 [ 36.3 % ] dead or severely disabled ; 1.05 , 0.99 - 1.10 ; p=0.079 ) . There was no evidence that the effect of corticosteroids differed by injury severity or time since injury . These results lend support to our earlier conclusion that corticosteroids should not be used routinely in the treatment of head injury 10 percent glycerol was given for 6 days to 30 patients who had had acute ischaemic cerebral infa rct ion , and the results were compared with those obtained after treating 31 similar patients with dexamethasone ( 16 mg . per 24 hours for 6 days ) . 1 patient treated with glycerol died of haemoglobinuria and acute renal failure . 6 patients treated with dexamethasone died--3 from cerebral oedema and 3 from non-neurological complications ( pulmonary embolism , myocardial infa rct ion , and aspiration pneumonia ) . Improvement was significantly greater in the glycerol group after 8 and 15 days . No improvement was noted using either glycerol or dexamethasone in 7 patients with spontaneous intracerebral haemorrhage Over 13 months 118 patients admitted to hospital with acute stroke were allocated at r and om to treatment with either dexamethasone or placebo . At one year there was no significant difference in the numbers of survivors or in the quality of life between the two groups . The results suggest that there is no indication for the routine administration of dexamethasone to a heterogeneous group of patients with stroke To evaluate the efficacy of dexamethasone for treatment of primary supratentorial intracerebral hemorrhage , we studied 93 patients 40 to 80 years old , using a double-blind r and omized block design . After the subjects were stratified according to their level of consciousness ( Glasgow Coma Scale ) , those with objective ly documented primary supratentorial intracerebral hemorrhage were r and omly assigned to either dexamethasone or placebo . For ethical reasons , three interim analyses were planned , to permit early termination of the trial if one study group did better than the other . During the third interim analysis , the death rate at the 21st day was identical in the two groups ( dexamethasone vs. placebo , 21 of 46 vs. 21 of 47 ; chi-square = 0.01 , P = 0.93 ) . In contrast , the rate of complications ( mostly infections and complications of diabetes ) was much higher in the dexamethasone group ( chi-square = 10.89 , P less than 0.001 ) , leading to early termination of the study . In the light of the absence of a demonstrable beneficial effect and the presence of a significant harmful effect , current practice s of using dexamethasone for treatment of primary supratentorial hemorrhage should be reconsidered |
12,192 | 18,709,888 | Association of dietary intake levels of B vitamins with age-related neurodegenerative diseases and cognitive | Age-related neurocognitive disorders , primarily Alzheimer ’s disease and Parkinson ’s disease , have a major impact on health and well-being [ 1 ] .
Separate lines of evidence have suggested that B vitamin status may be associated with risk and progression of Alzheimer ’s disease and Parkinson ’s disease .
This report summarizes the evidence for relationships between B vitamin status and supplementation and age-related neurocognitive disorders . | BACKGROUND Elevated plasma total homocysteine concentration may be a risk factor for cognitive decline and Alzheimer disease , but data from prospect i ve studies are limited . Further , high homocysteine levels are associated with low vitamin status , and it is unknown whether it is homocysteine toxicity or vitamin insufficiency that is responsible for the observed cognitive dysfunction . METHODS We performed cross-sectional and longitudinal analyses of a cohort of 499 high-functioning community-dwelling persons aged 70 to 79 years to determine the effect of homocysteine and related vitamin plasma concentrations on cognitive function and cognitive decline . Nonfasting plasma concentrations of homocysteine , folate , vitamin B(6 ) , and vitamin B(12 ) were measured at baseline . Summary measures of cognitive function were created from tests of multiple cognitive domains administered at baseline and again after 7 years . RESULTS In cross-sectional analyses investigating each variable separately , subjects with elevated homocysteine levels , or low levels of folate or vitamin B(6 ) , demonstrated worse baseline cognitive function . In longitudinal analyses , after adjusting for multiple covariates , including homocysteine , those in the bottom quartile of folate had a 1.6-fold increased risk ( 95 % confidence interval : 1.01 to 2.31 ; P = 0.04 ) of being in the worst quartile of 7-year cognitive decline . Low folate levels largely accounted for a trend towards greater cognitive decline with elevated homocysteine level . CONCLUSION In high-functioning older adults , low folate levels appear to be a risk factor for cognitive decline . The risk of developing cognitive decline might be reduced through dietary folate intake Based on research demonstrating associations between folate , B-12 and B-6 vitamins and cognition and mood , we investigated the effects of short-term supplementation in 211 healthy younger , middle-aged and older women who took either 750 microg of folate , 15 microg of vitamin B-12 , 75 mg of vitamin B-6 or a placebo daily for 35 d. In addition , we examined associations between dietary intake of these vitamins and cognition and mood . Usual dietary intake status was estimated using a retrospective , self-report , quantified food frequency question naire . Participants completed alternate forms of st and ardized tests of cognitive processing re sources , memory , executive function , verbal ability and self-report mood measures before and after supplementation . Supplementation had a significant positive effect on some measures of memory performance only , and no effect on mood . Dietary intake status was associated with speed of processing , recall and recognition and verbal ability BACKGROUND Deficiencies of vitamin B-12 , folic acid , and vitamin B-6-as defined by laboratory measures -occur in 10 - 20 % of elderly subjects . The clinical significance remains unresolved . OBJECTIVE The objective was to explore any association between vitamin status and vitamin treatment and movement and cognitive performance in elderly subjects . DESIGN Community-dwelling subjects ( n = 209 ) with a median age of 76 y were r and omly assigned to daily oral treatment with 0.5 mg cyanocobalamin , 0.8 mg folic acid , and 3 mg vitamin B-6 or placebo ( double blind ) for 4 mo . Movement and cognitive performance tests were performed before and after treatment . RESULTS A high plasma total homocysteine ( tHcy ) concentration ( > or = 16 micromol/L ) was found in 64 % of men and in 45 % of women , and a high serum methylmalonic acid ( MMA ) concentration ( > or = 0.34 micromol/L ) was found in 11 % of both sexes . Movement time , digit symbol , and block design ( adjusted for age , sex , smoking , and creatinine ) correlated independently with plasma tHcy ( P < 0.01 , < 0.05 , and < 0.01 , respectively ) ; the simultaneity index and block design correlated with serum MMA ( P < 0.05 for both ) . Vitamin therapy significantly decreased plasma tHcy ( 32 % ) and serum MMA ( 14 % ) . No improvements were found in the movement or cognitive tests compared with placebo . Neither vitamin therapy nor changes in plasma tHcy , serum MMA , serum vitamin B-12 , plasma folate , or whole-blood folate correlated with changes in movement or cognitive performance . CONCLUSIONS High plasma tHcy and serum MMA were prevalent and correlated inversely with movement and cognitive performance . Oral B vitamin treatment normalized plasma tHcy and serum MMA concentrations but did not affect movement or cognitive performance . This might have been due to irreversible or vitamin-independent neurocognitive decline or to an insufficient dose or duration of vitamins OBJECTIVE To explore the associations of low serum levels of vitamin B(12 ) and folate with AD occurrence . METHODS A population -based longitudinal study in Sweden , the Kungsholmen PROJECT A r and om sample of 370 nondemented persons , aged 75 years and older and not treated with B(12 ) and folate , was followed for 3 years to detect incident AD cases . Two cut-off points were used to define low levels of vitamin B(12 ) ( < or = 150 and < or = 250 pmol/L ) and folate ( < or = 10 and < or = 12 nmol/L ) , and all analyses were performed using both definitions . AD and other types of dementia were diagnosed by specialists according to DSM-III-R criteria . RESULTS When using B(12 ) < or = 150 pmol/L and folate < or = 10 nmol/L to define low levels , compared with people with normal levels of both vitamins , subjects with low levels of B(12 ) or folate had twice higher risks of developing AD ( relative risk [ RR ] = 2.1 , 95 % CI = 1.2 to 3.5 ) . These associations were even stronger in subjects with good baseline cognition ( RR = 3.1 , 95 % CI = 1.1 to 8.4 ) . Similar relative risks of AD were found in subjects with low levels of B(12 ) or folate and among those with both vitamins at low levels . A comparable pattern was detected when low vitamin levels were defined as B(12 ) < or = 250 pmol/L and folate < or = 12 nmol/L. CONCLUSIONS This study suggests that vitamin B(12 ) and folate may be involved in the development of AD . A clear association was detected only when both vitamins were taken into account , especially among the cognitively intact subjects . No interaction was found between the two vitamins . Monitoring serum B(12 ) and folate concentration in the elderly may be relevant for prevention of AD BACKGROUND Associations between vitamin B-12 deficiency and impaired cognitive function and depression have been reported . METHODS A r and omized placebo controlled study including 140 individuals with an increased plasma methylmalonic acid ( 0.40 - 2.00 micromol/l ) not previously treated with vitamin B-12 . Cognitive function was assessed by the Cambridge Cognitive Examination ( CAMCOG ) , Mini-Mental State Examination ( MMSE ) , and a 12-words learning test . Symptoms of depression were evaluated by the Major Depression Inventory . The main outcome measure was change in cognitive function and depression score from baseline to follow-up 3 months later . RESULTS At baseline 78 ( 56 % ) individuals had cognitive impairment judged from the CAMCOG score and 40 ( 29 % ) according to the MMSE ; 18 ( 13 % ) individuals had symptoms of depression . No improvement was found in cognitive function comparing the treatment and placebo group ( total CAMCOG score : P = 0.43 ) , nor among individuals with only slightly impaired cognitive function ( n = 44 , total CAMCOG score : P = 0.42 ) . The treatment group did not improve in depression score as compared to the placebo group ( P = 0.18 ) . LIMITATIONS The duration of impaired cognitive function was unknown . CONCLUSIONS A high proportion of individuals with an increased plasma methylmalonic acid had impaired cognitive function , and a rather high prevalence of depression was observed . However , vitamin B-12 treatment did not improve cognitive function or symptoms of depression within the 3-months study period Routine determination of serum vitamin B12 levels is generally recommended as part of the screening of demented patients , based on the notion that vitamin B12 deficiency is one of the causes of reversible dementia . We studied the effects of vitamin B12 replacement therapy in a prospect i ve longitudinal study at a memory clinic , with special emphasis on assessment of severity of dementia : not only cognitive deterioration , but also disability in the activities of daily life , behavioural problems , and the burden experienced by the caregiver were examined using instruments of proven validity . In a series of 170 consecutive patients with dementia , subnormal serum vitamin B12 levels were found in 26 cases ( 15 % ) ; all but one fulfilled diagnostic criteria for possible Alzheimer 's disease . Cobalamin supplementation was given to all patients and the effect was evaluated after 6 months . When the size and pattern of individual change scores , and the mean change scores on all instruments were taken into account , functioning after replacement therapy was not improved . When change scores of treated patients were compared with those of patients with Alzheimer 's disease ( n = 69 ) , vitamin B12 replacement did not result in slowing of the progression of dementia . Contrary to widely accepted beliefs , subnormal serum vitamin B12 levels are not a ( quantitatively ) important cause of reversible dementia BACKGROUND Associations between low levels of folate and vitamin B12 and cognitive impairment in patients with dementia have been reported . Some studies revealed correlations between low levels of vitamin B12 and behavioural and psychological signs and symptoms of dementia ( BPSD ) in Alzheimer 's disease ( AD ) patients . Given the lack of studies in frontotemporal dementia ( FTD ) and on folate and given the method ological shortcomings of former publications , we set up a prospect i ve study . METHODS At inclusion , AD ( n=152 ) and FTD ( n=28 ) patients underwent a neuropsychological examination . Behaviour was assessed using a battery of behavioural assessment scales . Determination of serum vitamin B12 and red cell folate levels were performed within a time frame of two weeks of inclusion . RESULTS In both patient groups , significantly negative correlations between levels of serum vitamin B12 and red cell folate and the degree of cognitive deterioration were found . No correlations with BPSD were found in the AD patient group . In FTD patients , levels of vitamin B12 were negatively correlated with both hallucinations ( p=0.022 ) and diurnal rhythm disturbances ( p=0.036 ) . CONCLUSIONS The observed negative correlations between levels of vitamin B12 and folate and cognitive impairment in both AD and FTD patients , raise the possibility of a non-specific etiological role . Although levels of vitamin B12 and folate did not correlate with BPSD in AD patients , negative correlations between serum vitamin B12 levels and BPSD in FTD patients were revealed . Decreased serum vitamin B12 levels may predispose FTD patients to develop hallucinations and diurnal rhythm disturbances BACKGROUND Mild cobalamin ( Cbl ) deficiency is frequently found in older persons and is associated with cognitive and cerebral abnormalities . The effects of Cbl supplementation on these abnormalities are largely unknown . METHODS In a single-blind , placebo-controlled intervention study , 16 healthy community-dwelling elderly subjects with low plasma Cbl concentration and no cognitive impairments were studied . Subjects underwent 1 month of treatment with placebo , followed by 5 months of treatment with intramuscular injections of hydroxycobalamin . Before and after measurements of plasma cobalamin , total homocysteine ( tHcy ) , methylmalonic acid ( MMA ) , quantitative electroencephalograph ( qEEG ) , and psychometric tests were taken . RESULTS After Cbl supplementation , plasma Cbl concentrations increased , and plasma MMA and tHcy concentrations decreased . The performance on the Verbal Word Learning Test , Verbal Fluency and Similarities improved . qEEG showed more fast activity and less slow activity . Lower plasma tHcy concentrations were related to increased fast activity on qEEG on the one h and and improved performance on the Verbal Word Learning Test and Similarities on the other . Increased fast or decreased slow activity on qEEG was associated with improved performance on the Verbal Word Learning Test , Similarities and Verbal Fluency . CONCLUSIONS Electrographic signs of improved cerebral function and improved cognitive function were found after Cbl supplementation in older subjects with low plasma Cbl concentrations who were free of significant cognitive impairment . These improvements were related to a reduction of plasma tHcy concentration OBJECTIVES To investigate the effect of cobalamin/folate supplementation on cognitive function in elderly patients with dementia . METHOD The cobalamin/folate status of the patients was evaluated by measuring plasma homocysteine , serum methylmalonic acid , serum cobalamin and blood folate . Thirty-three patients were studied and repeatedly assessed with the Mini-Mental State Examination ( MMSE ) and ' A short cognitive performance test for assessing memory and attention ' ( SKT ) during vitamin substitution . RESULTS Patients with mild-moderate dementia and elevated plasma homocysteine levels improved clinical ly with increased test scores after vitamin substitution , while severely demented patients and patients with normal plasma homocysteine levels did not improve clinical ly . CONCLUSIONS Plasma homocysteine may be the best marker for detecting treatable cobalamin/folate deficiency in patients with dementia Recent epidemiologic studies have shown an association between low serum folate levels and risk of vascular disease , including stroke and various types of vascular cognitive impairment . We examined data from the Canadian Study of Health and Aging ( CSHA ) , a population -based , prospect i ve 5-year investigation of the epidemiology of dementia among Canadians aged 65 + years . The risk of an adverse cerebrovascular event ( including vascular dementia , vascular cognitive impairment , or fatal stroke ) during follow-up , was assessed according to serum folate quartiles among subjects with no evidence of dementia at baseline ( n = 369 ) . After adjusting for certain covariates , including cardiovascular disease and nutritional indices , education , smoking and baseline cognitive status , the risk estimate for an adverse cerebrovascular event associated with the lowest folate quartile compared with the highest quartile was OR 2.42 ( 95 % CI 1.04–5.61 ) . Results from stratified analyses also showed that relatively low serum folate was associated with a significantly higher risk of an adverse cerebrovascular event among female ( OR 4.02 , 95 % CI 1.37–11.81 ) but not male ( OR 1.02 , 95 % CI 0.25–4.13 ) subjects . Among the total sample , there was a consistent trend toward poorer health and cognitive outcomes during follow-up ( including mortality , cognitive decline and dementia ) among those in the lowest folate quartile compared with the highest quartile . Low serum folate levels are independently associated with a significantly higher risk of an adverse cerebrovascular event , including vascular dementia and stroke death , among older , cognitively vulnerable persons Objective : To study the differences in cognitive status with respect to food habits and energy and nutrient intake in a group of non institutionalised , elderly people . Design : Prospect i ve study . Setting : The study subjects were independently living , elderly people who spent some of their time at day centres in the Comunidad de Madrid ( the Madrid region ) . The study centres were selected by the Madrid City Hall . Subjects : The study included 168 elderly people aged 65–90 y. All accepted the invitation to participate , met all inclusion criteria , and were free of significant cognitive impairment . Interventions : Dietary intake was monitored using a ‘ food record ’ for 7 consecutive days including a Sunday . In addition , the ‘ precise individual weighing ’ method was used for 5 days in order to monitor the meals taken by the subjects at the centres ' canteens . Cognitive capacity was measured using Folstein 's mini-mental state examination ( MMSE ) , vali date d for the Spanish population . Results : Subjects with an adequate cognitive capacity ( MMSE≥28 ) showed a greater intake of total foods , fish , and alcoholic drinks , but took less foods from the ‘ various ’ group ( chocolates , cakes , etc ) . These subjects had a more adequate intake of fatty acids and cholesterol , and a greater intake of vitamins implicated in correct brain function ( thiamine , folic acid , vitamin C ) . Conclusions : Subjects with satisfactory intellectual function generally had a better diet . This shows the importance of correct nutrition in its maintenance OBJECTIVES To examine the association of cognitive impairment with platelet activation and reactive oxygen species and total homocysteine levels ; and to assess the biochemical efficacy of treatment with aspirin and vitamin supplements in people at high risk of dementia . SUBJECTS People with dementia or mild cognitive impairment . DESIGN AND INTERVENTION In a 2 x 2 x 2 factorial design trial , 149 people at high-risk of dementia were r and omized to receive either low-dose aspirin ( 81 mg ) or placebo ; and folic acid ( 2 mg ) plus vitamin B12 ( 1 mg ) or placebo ; and vitamins E ( 500 mg ) plus C ( 200 mg ) or placebo . Participants were seen twice before and once after 12 weeks of treatment . MAIN OUTCOME MEASURES At each visit , participants had their cognitive function assessed and had blood collected for homocysteine , folate and vitamin B12 determination and urine collected for markers of platelet activation ( 11-dehydro-thromboxane B2 ) and reactive oxygen species ( 8-epi-PGF2 alpha ) . RESULTS Prior to treatment , cognitive function was inversely related with homocysteine and with urinary thromboxane and isoprostane , and these associations were independent of age . Aspirin was associated with a median reduction in 11-dehydrothromboxane B2 of 73 % ( P < 0.001 ) . B-vitamins lowered plasma homocysteine concentration by 30 % ( P < 0.0001 ) and antioxidant vitamins lowered isoprostane excretion by 26 % ( P < 0.1 ) . No effect of treatment on cognitive function was detected . CONCLUSIONS Aspirin and B-vitamins were effective in reducing biochemical factors associated with cognitive impairment in people at risk of dementia . Large-scale trials are now required to assess the relevance of aspirin and B-vitamins for the maintenance of cognitive function in people at risk of dementia Recent work on high plasma homocysteine levels in patients at risk for developing Alzheimer 's disease has led to the hypothesis that folic acid supplementation might reduce risk in such patients . The authors report on the effects of folic acid 10 mg/day versus placebo on 11 patients ( only 7 completers ) with dementia and low-normal folic acid levels . This is the first study evaluating folic acid or placebo in patients with dementia . Subjects had low-normal baseline folic acid levels . The magnitude of change between baseline and second testing was not statistically significant between the 2 groups . However , there was a trend for the folate group to perform worse on two specific cognitive measures , suggesting a possible trend toward worsening of some cognitive abilities after the folic acid . The folic acid in very high doses was well tolerated . Larger studies are necessary before empirically administering folic acid to patients already suffering from dementia . ( J Geriatr Psychiatry Neurol 2003 ; 16:156 - 159 ) OBJECTIVE Authors determined the impact of high-dose vitamin supplements on plasma homocysteine levels in patients with Alzheimer disease ( AD ) . METHODS Authors used an open-label trial of folic acid , vitamin B(12 ) , and vitamin B(6 ) , in combination for 8 weeks , with measurement of plasma homocysteine levels in the fasting state and after methionine-loading . A total of 69 subjects with AD were enrolled , including 33 who were taking st and ard multivitamin supplements ; 66 were available at 8-week follow-up . RESULTS The high-dose vitamin regimen was associated with a significant reduction in fasting and post-methionine-loading homocysteine . Reductions were greater in the subgroup not using multivitamins , but were also significant in the multivitamin users . CONCLUSION High-dose vitamin supplementation reduces homocysteine levels in patients with AD . The effect of supplementation on rate of cognitive decline will be assessed later in a r and omized , double-blind study We examined individual-difference variables in relation to the rate of change in global cognitive performance , measured by the MMSE , from 3 years prior to diagnosis of Alzheimer 's disease ( AD ) to the time of diagnosis . The population -based sample consisted of 230 incident AD persons who were followed over a 3-year interval . The average annual decline in MMSE was 1.81 points . Being older and acquiring additional diseases during the 3 years preceding diagnosis predicted a faster rate of decline in global cognitive functioning . However , other individual difference variables such as sex , education , depression , vitamin levels ( vitamin B12 and folic acid ) , apolipoprotein status , and social network did not precipitate the rate of decline in the pre clinical phase of AD OBJECTIVES To determine the effect of small doses of oral cyanocobalamin supplements in older patients with low or borderline serum vitamin B12 concentrations but no other evidence of pernicious anemia ( PA ) . DESIGN R and omized , double-blind , placebo-controlled study assessing the efficacy of oral cyanocobalamin 10 microg and 50 microg daily for 1 month . SETTING Two geriatric hospitals in the North Western Health Care Network , Melbourne , Australia . PARTICIPANTS Thirty-one in patients with serum vitamin B12 levels between 100 and 150 pmol/L , without PA , other malabsorption disorders , or progressive neurological or terminal illness . The mean age was 81.4 years . INTERVENTION After informed consent , a medical and drug history was taken and the Mini-Mental State Examination ( MMSE ) completed . A dietitian made assessment of oral cobalamin intake . Blood was taken for serum vitamin B12 , serum and red cell folate assay , full blood examination , fasting serum gastrin , parietal and intrinsic factor antibodies , fasting serum homocysteine , and creatinine . Patients were then r and omized to receive 10 microg oral cyanocobalamin , 50 microg oral cyanocobalamin , or placebo treatment for 1 month , after which the investigations and clinical examinations were repeated . MEASUREMENTS Percentage change in the level of vitamin B12 , homocysteine , folate , and red cell parameters and absolute changes in MMSE were calculated and compared between groups . The groups were compared on the number of responders who improved their level of B12 by 20 % . Chi-square calculations on changes in serum vitamin B12 concentration were also performed . RESULTS Mean serum vitamin B12 + /- st and ard deviation improved by 51.7 + /- 47.1 % in the 50-microg group , 40.2 + /- 34.4 % in the 10-microg group , and 11.7 + /- 24.5 % in the placebo group . The change in the 50-microg cyanocobalamin group was significantly greater than that in the placebo group ( P=.044 ) . The change in the 10-microg cyanocobalamin group was not significantly different from that in the placebo group ( P=.186 ) . Eight of 10 subjects in each treatment group were classified as responders , compared with two of 11 in the placebo group ( P=.004 ) . Homocysteine levels fell in patients receiving cyanocobalamin , but this fall failed to reach statistical significance . There were no significant changes in the other parameters measured . CONCLUSION Cyanocobalamin supplementation of 50 microg but not 10 microg daily produced a significant increase in serum vitamin B12 . This result has implication s for the management of patients with subnormal or borderline serum vitamin B12 concentrations and for food fortification with vitamin B12 We examined the relationship between dietary intake and cognitive performance in Korean elderly people . Data for dietary intake , anthropometric measurements and cognitive function tests were collected and the relationships of the variables were analyzed . A r and om sample of 210 men and 239 women in Korea , aged 60 and over , was selected . Subjects were free-living elderly people who had not experienced major cognitive function impairment . Main outcome measures , 24 h dietary recall method , food behaviour variables , anthropometrics indices , health variables , and Kwon 's Mini-Mental State Examination for Koreans ( MMSE-K ) for cognitive function test . The prevalence rate of poor cognitive function ( MMSE-K score < or = 19 ) of Korean elderly was 22.3 % : women with poor cognitive function had a higher rate ( 31.0 % ) than that in men ( 12.3 % ) . Cognitive ability was related negatively with age and positively with school education level . Female subjects of poor cognitive function had significantly lower intakes of total amount of foods , cereals , vegetables , fruits , milk , spices , and also , energy , protein , fat , carbohydrate , Ca , P , Fe , vitamin A , thiamin , riboflavin , and niacin than those of the normal cognitive score ( > or = 24 ) group ( P < 0.05 ) . Male subjects of poor cognitive function had significantly lower intakes of fruits , fiber , and vitamin C than the normal subjects ( P < 0.05 ) . The MMSE-K score of female subjects showed a significant positive correlation with total amount of foods , cereals , beans , fruits , milk , oil , spices , and energy , protein , fat , carbohydrate , Ca , Fe , P , riboflavin and niacin intakes . The consumption of adequate nutrients , by taking sufficient amounts and variety of foods , may be important in maintaining adequate cognitive function in elderly Koreans BACKGROUND Low serum cobalamin levels are often found in apparently normal older subjects . A major worry of leaving cobalamin deficiency untreated is that it may lead to subtle deterioration in cognitive function . OBJECTIVES To investigate the effect of supplementation on the cognitive function of older people with cobalamin deficiency by a r and omized trial . METHODS Fifty Chinese subjects more than 60 years old with serum cobalamin level < 120 pmol/l were r and omized into supplement and control groups . Fasting serum methylmalonic acid levels ( MMA ) were measured . A battery of neuropsychological tests was administered . The supplement group received intramuscular cyanocobalamin injections , while the control group received no intervention . They were followed up at around 4 months . RESULTS 78 % of the subjects had raised MMA , indicating metabolic cobalamin deficiency . Supplemented subjects improved in performance IQ , but the amount of improvement was not significantly more than that of control subjects . Moreover , the supplement group fared worse than the control group at follow-up in some motor function scores . Three out of seven demented subjects had improvement in Mini-Mental State Examination scores , but there was no consistent improvement in other neuropsychological scores . CONCLUSIONS This study suggested that cobalamin deficiency did not invariably cause cognitive impairment in older people . There remain the possibilities that cobalamin deficiency causes cognitive impairment or exacerbates coexisting dementia in some older people BACKGROUND Deficiencies in folate and vitamin B12 have been associated with neurodegenerative disease . OBJECTIVE To examine the association between rates of age-related cognitive change and dietary intakes of folate and vitamin B12 . DESIGN Prospect i ve study performed from 1993 to 2002 . SETTING Geographically defined biracial community in Chicago , Ill. PARTICIPANTS A total of 3718 residents , 65 years and older , who completed 2 to 3 cognitive assessment s and a food frequency question naire . MAIN OUTCOME MEASURE Change in cognitive function measured at baseline and 3-year and 6-year follow-ups , using the average z score of 4 tests : the East Boston Tests of immediate and delayed recall , the Mini-Mental State Examination , and the Symbol Digit Modalities Test . RESULTS High folate intake was associated with a faster rate of cognitive decline in mixed models adjusted for multiple risk factors . The rate of cognitive decline among persons in the top fifth of total folate intake ( median , 742 microg/d ) was more than twice that of those in the lowest fifth of intake ( median , 186 microg/d ) , a statistically significant difference of 0.02 st and ardized unit per year ( P = .002 ) . A faster rate of cognitive decline was also associated with high folate intake from food ( P for trend = .04 ) and with folate vitamin supplementation of more than 400 microg/d compared with nonusers ( beta = -.03 , P<.001 ) . High total B12 intake was associated with slower cognitive decline only among the oldest participants . CONCLUSIONS High intake of folate may be associated with cognitive decline in older persons . These unexpected findings call for further study of the cognitive implication s of high levels of dietary folate in older population OBJECTIVE To examine the effects of cobalamin repletion on cognition in elderly subjects with low serum cobalamin and evidence of cognitive dysfunction . DESIGN Time series data collected in an open trial of parenteral cobalamin therapy . SETTING S Outpatient geriatric assessment centers , inpatient geropsychiatry unit , and tertiary care university hospital . PARTICIPANTS Twenty-two subjects with low serum cobalamin ( less than 150 pmol/L ) and evidence of cognitive dysfunction were entered consecutively over an 8-month period of time . Eighteen subjects completed the study . INTERVENTIONS Subjects received 1000 micrograms of cyanocobalamin intramuscularly daily for 1 week , then weekly for 1 month , then monthly thereafter for a minimum of six months . OUTPATIENT MEASURE : The Mattis Dementia Rating Scale ( DRS ) was administered both before and at least 6 months after full cobalamin replacement therapy . The hypothesis that cognitive improvement was dependent on the duration of cognitive symptoms was formulated a posteriori . RESULTS After a minimum of 6 months of cobalamin therapy , 11 of 18 patients showed cognitive improvement . There was a striking correlation between duration of cognitive symptoms and response to therapy . Patients symptomatic for less than 12 months gained an average of twenty points on the DRS ( paired t test P = 0.0076 ) , whereas patients symptomatic greater than 12 months lost an average of three points ( paired t test P = .34 ) . Two patients symptomatic for only 3 months normalized their DRS scores , gaining 31 and 28 points , respectively . CONCLUSION There may be a time-limited window of opportunity for effective intervention in patients with cognitive dysfunction and low serum cobalamin |
12,193 | 26,292,609 | Overall results suggest that l and ing biomechanics are altered with some brace types but studies disagree as to the particular variables affected .
There is evidence that ankle bracing may alter lower-extremity l and ing biomechanics in a manner which predisposes athletes to injury . | OBJECTIVES To examine the evidence for effect of ankle bracing on lower-extremity l and ing biomechanics . | OBJECTIVES To investigate the effect of bracing and taping on selected electromyographic , kinematic , and kinetic variables when l and ing from a jump . METHODS Fifteen netball players performed a jump , so as to l and on their dominant limb on a force plate . Electromyographic activity was recorded from the gastrocnemius , tibialis anterior , and peroneus longus muscles . Subjects were also filmed and measures of rearfoot motion were derived . RESULTS Significantly less electromyographic activity ( p<0.007 ) was observed from the gastrocnemius and peroneus longus muscle groups when subjects were braced . No other significant electromyographical findings were observed . Peak vertical ground reaction force and time to peak for vertical ground reaction force were not affected by bracing and taping , nor were the rearfoot and Achilles tendon angles at foot strike . CONCLUSIONS The effect of bracing and taping on the selected biomechanics variables associated with l and ing was specifically limited to a reduction in muscle action , particularly for the braced condition . Netball players can be confident that the biomechanics of their l and ing patterns will not be altered whether they choose to wear a brace or tape their ankle joints PURPOSE Ankle joint dorsiflexion contributes to energy absorption during l and ing , but wearing ankle stabilizers is known to restrict passive measures of dorsiflexion . This study compared the effects of various ankle stabilizers on ankle joint kinematics during soft and stiff l and ings . METHODS Subjects ( N = 14 ) performed two-legged l and ings off a 0.59-m platform . Kinematics of the right ankle were calculated from a sagittal plane video recording ( 120 Hz ) . Five soft and five stiff l and ings were performed in five ankle stabilizer conditions ( no stabilizer , taping , Swede-O , AirCast , and Active Ankle ) , a total of 50 trials per subject . Style and stabilizer conditions were r and omized across subjects . Each subject 's five-trial mean value of selected kinematic variables for each l and ing style/stabilizer condition was entered into a two-way repeated MANOVA ( alpha = 0.05 ) . RESULTS Differences between soft and stiff l and ing conditions were similar to those reported in the literature . Compared with the No stabilizer condition , most stabilizer conditions significantly reduced ankle dorsiflexion ROM and angular velocity during l and ing . CONCLUSIONS The results indicate that some ankle stabilizers adversely affect ankle joint kinematics during l and ing BACKGROUND Lower extremity stiffness is thought to be an important factor in musculoskeletal performance . However , too little or too much stiffness is believed to increase the risk of musculoskeletal injury . PURPOSE To provide a current up date of the lower extremity stiffness literature as it pertains to both performance and injury . SUMMARY It appears that increased stiffness is beneficial to performance . As well it appears that there may be an optimal amount of stiffness that allows for injury-free performance . There is some evidence that increased stiffness may be related to bony injuries and decreased stiffness may be associated with soft tissue injuries . Further investigations should evaluate the relationship between stiffness and injury prospect ively . Initial reports suggest that stiffness can be modified in response to the external environment or verbal cues . RELEVANCE A greater underst and ing of the role of stiffness in both performance and injury will provide a stronger foundation for the development of optimal training intervention programs 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 Objectives : To determine if measurements of static lower limb alignment are related to lower limb injury in recreational runners . Methods : Static lower limb alignment was prospect ively measured in 87 recreational runners . They were observed for the following six months for any running related musculoskeletal injuries of the lower limb . Injuries were defined according to six types : R1 , R2 , and R3 injuries caused a reduction in running mileage for one day , two to seven days , or more than seven days respectively ; S1 , S2 , and S3 injuries caused stoppage of running for one day , two to seven days , or more than seven days respectively . Results : At least one lower limb injury was suffered by 79 % of the runners during the observation period . When the data for all runners were pooled , 95 % confidence intervals calculated for the differences in the measurements of lower limb alignment between the injured and non-injured runners suggested that there were no differences . However , when only runners diagnosed with patellofemoral pain syndrome ( n = 6 ) were compared with non-injured runners , differences were found in right ankle dorsiflexion ( 0.3 to 6.1 ) , right knee genu varum ( −0.9 to −0.3 ) , and left forefoot varus ( −0.5 to −0.4 ) . Conclusions : In recreational runners , there is no evidence that static biomechanical alignment measurements of the lower limbs are related to lower limb injury except patellofemoral pain syndrome . However , the effect of static lower limb alignment may be injury specific CONTEXT Long-term effects of ankle bracing on lower extremity kinematics and kinetics are unknown . Ankle motion restriction may negatively affect the body 's ability to attenuate ground reaction forces ( GRFs ) . OBJECTIVE To evaluate the immediate and long-term effects of ankle bracing on lower extremity kinematics and GRFs during a jump l and ing . DESIGN Experimental mixed model ( 2 [ group ] x 2 [ brace ] x 2 [ time ] ) with repeated measures . SETTING Sports medicine research laboratory . PATIENTS OR OTHER PARTICIPANTS A total of 37 healthy subjects were assigned r and omly to either the intervention ( n = 11 men , 8 women ; age = 19.63 + /- 0.72 years , height = 176.05 + /- 10.58 cm , mass = 71.50 + /- 13.15 kg ) or control group ( n = 11 men , 7 women ; age = 19.94 + /- 1.44 years , height = 179.15 + /- 8.81 cm , mass = 74.10 + /- 10.33 kg ) . INTERVENTION(S ) The intervention group wore braces on both ankles and the control group did not wear braces during all recreational activities for an 8-week period . MAIN OUTCOME MEASURE(S ) Initial ground contact angles , maximum joint angles , time to reach maximum joint angles , and joint range of motion for sagittal-plane knee and ankle motion were measured during a jump-l and ing task . Peak vertical GRF and the time to reach peak vertical GRF were assessed also . RESULTS While participants were wearing the brace , ankle plantar flexion at initial ground contact ( brace = 35 degrees + /- 13 degrees , no brace = 38 degrees + /- 15 degrees , P = .024 ) , maximum dorsiflexion ( brace = 21 degrees + /- 7 degrees , no brace = 22 degrees + /- 6 degrees , P = .04 ) , dorsiflexion range of motion ( brace = 56 degrees + /- 14 degrees , no brace = 59 degrees + /- 16 degrees , P = .001 ) , and knee flexion range of motion ( brace = 79 degrees + /- 16 degrees , no brace = 82 degrees + /- 16 degrees , P = .036 ) decreased , whereas knee flexion at initial ground contact increased ( brace = 12 degrees + /- 9 degrees , no brace = 9 degrees + /- 9 degrees , P = .0001 ) . Wearing the brace for 8 weeks did not affect any of the outcome measures , and the brace caused no changes in vertical GRFs ( P > .05 ) . CONCLUSIONS Although ankle sagittal-plane motion was restricted with the brace , knee flexion upon l and ing increased and peak vertical GRF did not change . The type of lace-up brace used in this study appeared to restrict ankle motion without increasing knee extension or vertical GRFs and without changing kinematics or kinetics over time The purpose of this prospect i ve study was to determine whether an association exists between foot structure and the development of musculoskeletal overuse injuries . The study group was a well-defined cohort of 449 trainees at the Naval Special Warfare Training Center in Coronado , California . Before beginning training , measurements were made of ankle motion , subtalar motion , and the static ( st and ing ) and dynamic ( walking ) characteristics of the foot arch . The subjects were tracked prospect ively for injuries throughout training . We identified risk factors that predispose people to lower extremity overuse injuries . These risk factors include dynamic pes planus , pes cavus , restricted ankle dorsiflexion , and increased hindfoot inversion , all of which are subject to intervention and possible correction OBJECTIVE The aim of the present investigation was to test the stability of 10 different ankle braces under passive and rapidly induced loading conditions in a population suffering from chronic ankle instability in order to provide objective information to choose or recommend an appropriate model for specific needs . In addition , the relationship between passive and rapidly induced testing of the stabilizing effect against inversion was evaluated to identify if passive support characteristics of braces are reflected under rapidly induced conditions . DESIGN An experimental in vivo study with a repeated- measures design was used . BACKGROUND Ankle braces are commonly used for treatment , rehabilitation , and prevention of ankle injuries . A variety of products exists but there is few information available to assist clinicians , physiotherapists and coaches as well as consumers in choosing a brace on a basis of objective information . Furthermore , there is a lack of studies that provide data for both passively and rapidly induced movement of the ankle joint when using different ankle braces . METHODS Twenty-four subjects with chronic ankle instability participated in the project . Passive ankle range of motion measurements were performed in a custom-built fixture and simulated inversion sprains were elicited on a tilting platform . RESULTS The tested braces restrict range of motion significantly compared to the no-brace condition for both the passively and rapidly induced inversion and marked differences between braces were revealed . A close relationship between passive and rapidly induced test results for inversion was found . CONCLUSIONS Passive as well as rapidly induced stability tests provide a basis of objective information to describe the characteristics of different ankle braces . Combined results of passive and rapidly induced inversion as well as correlation between results demonstrate that passive support characteristics of braces are reflected under rapidly induced conditions but the amount of restriction is reduced . Therefore , caution should be taken when recommending braces for applications under dynamic circumstances only on the basis of passive support characteristics . RELEVANCE A basis of information regarding the stability characteristics of different ankle braces under passive and rapidly induced conditions will help the clinician and consumer in choosing the most appropriate brace model for specific use . The results also provide more insights into factors that influence stability characteristics of ankle braces STUDY DESIGN Single-group repeated- measures experimental design . OBJECTIVES The purpose of this study was to evaluate the effects of prophylactic ankle stabilization on vertical ground reaction forces before and after treadmill jogging . BACKGROUND Previous research has demonstrated acute effects of ankle taping and bracing on ankle joint kinematics and vertical ground reaction forces during drop l and ings . Based on the number of investigations demonstrating increased range of motion of the braced or taped ankle following exercise , it may be plausible that the aforementioned l and ing alterations may return to normal following an exercise bout . METHODS AND MEASURES Fourteen healthy recreational participants performed stiff and soft drop l and ings before and after a 20-minute treadmill exercise bout under 3 different ankle stabilizer conditions ( no stabilizer , ankle brace , and ankle tape ) . A forceplate was used to collect ground reaction force data under the dominant foot . The first and second peak impact force , as well as the time to each of the 2 peak forces , were determined for each trial and used as dependent variables . RESULTS The time to reach peak forces were significantly less under the ankle brace and tape conditions in comparison to the control ( no-stabilizer ) condition . CONCLUSIONS It appears that ankle taping and bracing decrease the time to reach peak impact forces . These alterations indicate that during dynamic activity the musculoskeletal structures of the body may be subjected to loads within shorter time periods . Whether these effects are detrimental over time remains speculative at this point and requires further research Background : Patellar tendinopathy ( PT ) is one of the most common reasons for sport-induced pain of the knee . Low ankle dorsiflexion range might predispose for PT because of load-bearing compensation in the patellar tendon . Purpose : The purpose of this 1-year prospect i ve study was to analyze if a low ankle dorsiflexion range increases the risk of developing PT for basketball players . Study Design : Cohort study ( prognosis ) ; Level of evidence , 2 . Methods : Ninety junior elite basketball players were examined for different characteristics and potential risk factors for PT , including ankle dorsiflexion range in the dominant and nondominant leg . Data were collected over a 1-year period and follow-up , including reexamination , was made at the end of the year . Results : Seventy-five players met the inclusion criteria . At the follow-up , 12 players ( 16.0 % ) had developed unilateral PT . These players were found to have had a significantly lower mean ankle dorsiflexion range at baseline than the healthy players , with a mean difference of −4.7 ° ( P = .038 ) for the dominant limb and −5.1 ° ( P = .024 ) for the nondominant limb . Complementary statistical analysis showed that players with dorsiflexion range less than 36.5 ° had a risk of 18.5 % to 29.4 % of developing PT within a year , as compared with 1.8 % to 2.1 % for players with dorsiflexion range greater than 36.5 ° . Limbs with a history of 2 or more ankle sprains had a slightly less mean ankle dorsiflexion range compared to those with 0 or 1 sprain ( mean difference , −1.5 ° to −2.5 ° ) , although this was only statistically significant for nondominant legs . Conclusion : This study clearly shows that low ankle dorsiflexion range is a risk factor for developing PT in basketball players . In the studied material , an ankle dorsiflexion range of 36.5 ° was found to be the most appropriate cutoff point for prognostic screening . This might be useful information in identifying at-risk individuals in basketball teams and enabling preventive actions . A history of ankle sprains might contribute to reduced ankle dorsiflexion range This study sought to determine if prophylactic ankle taping and bracing influenced vertical leg stiffness during hopping . Twenty healthy and physically active participants completed testing under three ankle stabilizer conditions , ankle tape , semi-rigid ankle brace or control ( no stabilizer ) during three separate sessions . Immediately following stabilizer application , participants completed an exercise bout prior to completing the hopping . Vertical ground reaction forces were collected during the hopping and were used to calculate vertical leg stiffness . No significant changes in vertical leg stiffness were revealed . These results are likely attributable to the exercise bout causing sufficient loosening of the stabilizers , concurrent proximal joint compensations and /or the possibility that the effect of ankle stabilizers on shock absorption during hopping is more subtle than the effects revealed during drop l and ings |
12,194 | 28,859,144 | While speed-related outcomes and crash events ( also with very low- quality evidence ) both increased under chronic sleep loss , discrepant findings were reported under conditions of acute total sleep deprivation . | Young drivers ( 18 - 24 years ) are over-represented in sleep-related crashes ( comprising one in five fatal crashes in developed countries ) primarily due to decreased sleep opportunity , lower tolerance for sleep loss , and ongoing maturation of brain areas associated with driving-related decision making .
Impaired driving performance is the proximal reason for most car crashes .
There is still a limited body of evidence examining the effects of sleep loss on young drivers ' performance , with discrepancies in the method ologies used , and in the definition of outcomes .
This study aim ed to identify the direction and magnitude of the effects of sleep loss on young drivers ' performance , and to appraise the quality of current evidence via a systematic review . | OBJECTIVES To inform the debate over whether human sleep can be chronically reduced without consequences , we conducted a dose-response chronic sleep restriction experiment in which waking neurobehavioral and sleep physiological functions were monitored and compared to those for total sleep deprivation . DESIGN The chronic sleep restriction experiment involved r and omization to one of three sleep doses ( 4 h , 6 h , or 8 h time in bed per night ) , which were maintained for 14 consecutive days . The total sleep deprivation experiment involved 3 nights without sleep ( 0 h time in bed ) . Each study also involved 3 baseline ( pre-deprivation ) days and 3 recovery days . SETTING Both experiments were conducted under st and ardized laboratory conditions with continuous behavioral , physiological and medical monitoring . PARTICIPANTS A total of n = 48 healthy adults ( ages 21 - 38 ) participated in the experiments . INTERVENTIONS Noctumal sleep periods were restricted to 8 h , 6 h or 4 h per day for 14 days , or to 0 h for 3 days . All other sleep was prohibited . RESULTS Chronic restriction of sleep periods to 4 h or 6 h per night over 14 consecutive days result ed in significant cumulative , dose-dependent deficits in cognitive performance on all tasks . Subjective sleepiness ratings showed an acute response to sleep restriction but only small further increases on subsequent days , and did not significantly differentiate the 6 h and 4 h conditions . Polysomnographic variables and delta power in the non-REM sleep EEG-a putative marker of sleep homeostasis -- displayed an acute response to sleep restriction with negligible further changes across the 14 restricted nights . Comparison of chronic sleep restriction to total sleep deprivation showed that the latter result ed in disproportionately large waking neurobehavioral and sleep delta power responses relative to how much sleep was lost . A statistical model revealed that , regardless of the mode of sleep deprivation , lapses in behavioral alertness were near-linearly related to the cumulative duration of wakefulness in excess of 15.84 h ( s.e . 0.73 h ) . CONCLUSIONS Since chronic restriction of sleep to 6 h or less per night produced cognitive performance deficits equivalent to up to 2 nights of total sleep deprivation , it appears that even relatively moderate sleep restriction can seriously impair waking neurobehavioral functions in healthy adults . Sleepiness ratings suggest that subjects were largely unaware of these increasing cognitive deficits , which may explain why the impact of chronic sleep restriction on waking cognitive functions is often assumed to be benign . Physiological sleep responses to chronic restriction did not mirror waking neurobehavioral responses , but cumulative wakefulness in excess of a 15.84 h predicted performance lapses across all four experimental conditions . This suggests that sleep debt is perhaps best understood as result ing in additional wakefulness that has a neurobiological " cost " which accumulates over time 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 A telephone survey was conducted of a r and om sample of New York State licensed drivers to determine the prevalence and circumstances of drowsy driving . Based on the survey responses , 54.6 % of the drivers had driven while drowsy within the past year ; 22.6 % had ever fallen asleep at the wheel without having a crash , 2.8 % had ever crashed when they fell asleep , and 1.9 % had crashed when driving while drowsy . Of the reported crashes due to driving while drowsy or falling asleep at the wheel , 82.5 % involved the driver alone in the vehicle , 60.0 % occurred between 11:00 p.m. and 7:00 a.m. 47.5 % were drive-off-road crashes , and 40.0 % occurred on a highway or expressway . Multiple regression analysis suggested that the following driver variables are predictive of an increased frequency of driving drowsy : demographic characteristics ( younger drivers , more education , and men ) ; sleep patterns ( fewer hours of sleep at night and greater frequency of trouble staying awake during the day ) ; work patterns ( greater frequency of driving for job and working rotating shifts ) ; and driving patterns ( greater number of miles driven annually and fewer number of hours a person can drive before becoming drowsy ) 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 a body of evidence is associated with a high risk of publication bias . Even when individual studies included in best- evidence summaries have a low risk of bias , publication bias can result in substantial overestimates of effect . Authors should suspect publication bias when available evidence comes from a number of small studies , most of which have been commercially funded . A number of approaches based on examination of the pattern of data are available to help assess publication bias . The most popular of these is the funnel plot ; all , however , have substantial limitations . Publication bias is likely frequent , and caution in the face of early results , particularly with small sample size and number of events , is warranted During long and monotonous driving at night , most drivers progressively show signs of visual fatigue and loss of vigilance . Their capacity to maintain adequate driving performance usually is affected and varies with the age of the driver . The main question is to know , on one h and , if occurrence of fatigue and drowsiness is accompanied by a modification in the driving performance of the driver and , on the other h and , if this relationship partially depends on the driver 's age . Forty-six male drivers , divided into three age categories : 20 - 30 , 40 - 50 , and 60 - 70 years , performed a 350-km motorway driving session at night on a driving simulator . Driving errors were measured in terms of number of running-off-the-road incidents ( RORI ) and large speed deviations . The evolution of physiological vigilance level was evaluated using electroencephalography ( EEG ) recording . In older drivers , in comparison with young and middle-aged drivers , the degradation of driving performance was correlated to the evolution of lower frequency waking EEG ( i.e. , theta ) . Contrary to young and middle-aged drivers , the deterioration of the vigilance level attested by EEG correlated with the increase in gravity of all studied driving errors in older drivers . Thus , depending on the age category considered , only part of the driving errors would constitute a relevant indication as for the occurrence of a state of low arousal We ran a r and omized cross-over design study under sleep-deprived and non-sleep-deprived driving conditions to test the effects of sleep restriction on real driving performance . The study was performed in a sleep laboratory and on an open French highway . Twenty-two healthy male subjects ( age = 21.5 + /- 2 years ; distance driven per year = 12,225 + /- 4739 km ( 7641 + /- 2962 miles ) [ mean + /- S.D. ] ) drove 1000 km ( 625 miles ) over 10 h during five 105 min sessions on an open highway . Self-rated fatigue and sleepiness before each session , number of inappropriate line crossings from video recordings and simple reaction time ( RT ) were measured . Total crossings increased after sleep restriction ( 535 crossings in the sleep-restricted condition versus 66 after non-restricted sleep ( incidence rate ratio ( IRR ) : 8.1 ; 95 % confidence interval ( 95 % CI ) : 3.2 - 20.5 ; p < 0.001 ) ) , from the first driving session . The interaction between the two factors ( conditionxtime of day ) was also significant ( F(5 , 105 ) = 3.229 ; p < 0.05 ) . Increasing sleepiness score was associated with increasing crossings during the next driving session in the sleep-restricted ( IRR : 1.9 ; 95 % CI : 1.4 - 2.4 ) but not in the non-restricted condition ( IRR : 1.0 ; 95 % CI : 0.8 - 1.3 ) . Increasing self-perceived fatigue was not associated with increasing crossings in either condition ( IRR : 0.95 ; 95 % CI : 0.93 - 0.98 and IRR : 1.0 ; 95 % CI : 0.98 - 1.02 ) . Rested subjects drove 1000 km with four shorts breaks with only a minor performance decrease . Sleep restriction induced important performance degradation even though time awake ( 8h ) and session driving times ( 105 min ) were relatively short . Major inter-individual differences were observed under sleep restriction . Performance degradation was associated with sleepiness and not fatigue . Sleepiness combined with fatigue significantly affected RT . Road safety campaigns should encourage drivers to avoid driving after sleep restriction , even on relatively short trips especially if they feel sleepy A novel task , combining simulated driving with subtraction , was compared in 26 participants ages 18 to 26 years ( M = 20.6 , SD = 2.3 ; 13 men ) . After two nights of 8.5 hr . in bed , participants performed a 30-min . driving and subtraction task followed by a 10-min . Psychomotor Vigilance Task . These tasks were repeated after two more nights of 8.5 hr . time in bed for the control group and 5 hours and 3 hours time in bed for the restricted group . The sensitivity of the task to moderate sleep loss was supported because impairment was seen on several dual-task variables whereas impairment was not observed on the Psychomotor Vigilance Task 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 In industrialized countries one-fifth of all traffic accidents can be ascribed to sleepiness behind the wheel . Driver sleepiness can have many causes , including the use of medicinal drugs or prolonged driving . The present study compared the effects of prolonged highway driving at night with driving impairment caused by alcohol . A cross-over balanced design tested 14 healthy young men who drove three sessions during night-time on the open road . The driving sessions were of 2 , 4 and 8 h ( 03:00 - 05:00 , 01:00 - 05:00 and 21:00 - 05:00 hours ) duration . St and ard deviation of lateral position ( SDLP , cm ) , measuring the weaving of the car in the last driving hour of each session , was the primary parameter . Only 2 h of continuous nocturnal driving were sufficient to produce driving impairment comparable to a blood alcohol concentration ( BAC ) of 0.05 % ; after 3 h of driving impairment corresponds to a BAC of 0.08 % . In conclusion , a maximum of two continuous nocturnal driving hours should be recommended Slowed eyelid closure coupled with increased duration and frequency of closure is associated with drowsiness . This study assessed the utility of two devices for automated measurement of slow eyelid closure in a st and ard poor performance condition ( alcohol ) and following 12-h sleep deprivation . Twenty-two healthy participants ( mean age=20.8 ( SD 1.9 ) years ) with no history of sleep disorders participated in the study . Participants underwent one baseline and one counterbalanced session each over two weeks ; one 24-hour period of sleep deprivation , and one daytime session during which alcohol was consumed after a normal night of sleep . Participants completed a test battery consisting of a 30-min simulated driving task , a 10-min Psychomotor Vigilance Task ( PVT ) and the Karolinska Sleepiness Scale ( KSS ) each in two baseline sessions , and in two r and omised , counterbalanced experimental sessions ; following sleep deprivation and following alcohol consumption . Eyelid closure was measured during both tasks using two automated devices ( Copilot and Optalert ™ ) . There was an increase in the proportion of time with eyelids closed and the Johns Drowsiness Score ( incorporating relative velocity of eyelid movements ) following sleep deprivation using Optalert ( p<0.05 for both ) . These measures correlated significantly with crashes , PVT lapses and subjective sleepiness ( r-values 0.46 - 0.69 , p<0.05 ) . No difference between the two sessions for PERCLOS recorded during the PVT or the driving task as measured by the Copilot . The duration of eyelid closure predicted frequent lapses following sleep deprivation ( which were equivalent to the average lapses at a blood alcohol concentration of 0.05 % - area under curve for ROC curve 0.87 , p<0.01 ) . The duration of time with slow eyelid closure , assessed by the automated devices , increased following sleep deprivation and was associated with deterioration in psychomotor performance and subjective sleepiness . Comprehensive algorithms inclusive of ocular parameters may be a better indicator of performance impairment following sleep loss |
12,195 | 24,003,971 | Based on RCTs , there was no significantly increased risk of blood transfusions with general anaesthesia .
The incidence of hypotension and the amount of fluid given were higher in the neuraxial anaesthesia groups .
General anaesthesia is associated with a higher blood loss than neuraxial anaesthesia .
However , based on high- quality studies , the need for blood transfusion was not greater .
The higher blood loss with general anaesthesia is therefore of uncertain clinical relevance | BACKGROUND Postpartum haemorrhage ( PPH ) remains a leading cause of maternal morbidity and mortality .
The odds for PPH were about eight times higher following general anaesthesia compared with neuraxial anaesthesia in a recent retrospective study .
We aim ed to conduct a systematic review and meta- analysis of the effect of type of anaesthesia ( general vs. neuraxial ) on estimated blood loss and transfusion requirements after caesarean section . | UNLABELLED We studied the in vitro effects of sevoflurane , isoflurane , and propofol anesthesia on platelet function . Thirty patients undergoing minor surgical procedures were divided into three groups ( n = 10 each ) . Induction of anesthesia was achieved by using 5 mg/kg thiopental i.v . , and 0.1 mg/kg vecuronium i.v . was used for muscle relaxation . Anesthesia maintenance was provided by sevoflurane in the first , isoflurane in the second , and propofol infusion in the third group with 70 % N2O in O2 . Hemoglobin , hematocrit , thrombocyte count , prothrombin time , activated partial thromboplastin time , international normalized ratio , arterial pH , von Willebr and factor , viscosity , platelet aggregation , and bleeding time were measured 1 h pre- , intra- , and postanesthesia . There was no difference among the platelet aggregation ratios of the pre- , intra- , and postoperative periods in the isoflurane group . The aggregation ratios in the sevoflurane and propofol groups were significantly reduced at intraoperative periods compared with preoperative values . Diminished aggregation values were also found 1 h postoperatively compared with the control values in the sevoflurane and propofol groups . We conclude that , in patients with a bleeding tendency during the intra- and early postoperative period , isoflurane may be preferred as a general anesthetic . IMPLICATION S In our study , using vacuum-operated tubes , we demonstrated that sevoflurane and propofol had a significant inhibitory effect on intraoperative and early postoperative platelet aggregation , whereas isoflurane had no effect . Therefore , isoflurane may be preferred as a general anesthetic in patients with a clinical ly relevant bleeding tendency SUMMARY The addition of 0.5 per cent of halothane vapour to a basic thiopentone , nitrous oxide , muscle relaxant anaesthetic technique does not increase blood loss at Caesarean section , does not affect the incidence of hypotension , and is likely to ensure unconsciousness . By permitting the administration of 50 per cent of oxygen with nitrous oxide , the condition of the newborn infant is likely to be improved . The use of 0.8 per cent of halothane vapour does not increase blood loss but is associated with a high incidence of hypotension and for this reason is not advisable Objective To determine the surgical and anaesthetic benefits and problems associated with the practice of routine exteriorisation of the uterus to facilitate repair at caesarean section Background There are no r and omized studies on neonatal outcome after spinal versus general anesthesia for cesarean delivery in preeclamptic patients with a nonreassuring fetal heart trace . This study examined both markers of neonatal hypoxia and maternal hemodynamics . Methods Seventy patients were r and omized to general ( n = 35 ) or spinal anesthesia ( n = 35 ) . The general anesthesia group received thiopentone , magnesium sulfate , and suxamethonium intravenously before intubation , followed by 50 % nitrous oxide in oxygen , 0.75–1.5 % isoflurane , and morphine after delivery . The target end-tidal partial pressure of carbon dioxide ( Pco2 ) was 30–34 mmHg . The spinal anesthesia group received 1.8 ml hyperbaric bupivacaine plus 10 & mgr;g fentanyl at the L3–L4 interspace . Heart rate and blood pressure were measured at specific time points . Hypotension was treated with ephedrine . Maternal arterial and neonatal umbilical arterial blood gas sample s were taken at delivery . Resuscitation requirements were recorded . Results In both groups , hemodynamic measures remained within acceptable limits . Spinal anesthesia patients required more ephedrine ( 13.7 vs. 2.7 mg ) . Maternal Paco2 was lower in the spinal group ( 28.9 vs. 32.4 mmHg ) . One-minute Apgar scores were lower after general anesthesia . Base deficit was greater ( 7.13 vs. 4.68 mEq/l ) and neonatal umbilical arterial pH was lower ( 7.20 vs. 7.23 ) after spinal anesthesia . Post hoc analysis showed that if maternal diastolic blood pressure on admission was greater than 110 mmHg , neonatal umbilical arterial base deficit was greater after spinal anesthesia . There was no difference in the number of patients with Apgar scores less than 7 at 1 or 5 min or umbilical arterial pH less than 7.2 or in the requirements for resuscitation . Conclusions In preeclamptic patients with a nonreassuring fetal heart trace , spinal anesthesia for cesarean delivery was associated with a greater mean neonatal umbilical arterial base deficit and a lower median umbilical arterial pH. The clinical significance remains to be established . Maternal hemodynamics were similar and acceptable with either anesthetic technique Objective To evaluate the maternal and fetal effects of three anesthetic methods used r and omly in women with severe preeclampsia who required cesarean delivery . Methods Eighty women with severe preeclampsia , who were to be delivered by cesarean , were r and omized to general ( 26 women ) , epidural ( 27 ) , or combined spinalepidural ( 27 ) anesthesia . The mean preoperative blood pressure ( BP ) was approximately 170/110 mmHg , and all women had proteinuria . Anesthetic and obstetric management included antihypertensive drug therapy and limited intravenous ( IV ) fluid and drug therapy . Results The mean gestational age at delivery was 34.8 weeks . All infants were born in good condition as assessed by Apgar scores and umbilical arterial blood gas determinations . Maternal hypotension result ing from regional anesthesia was managed without excessive IV fluid administration . Similarly , maternal BP was managed without severe hypertensive effects in women undergoing general anesthesia . There were no serious maternal or fetal complications attributable to any of the three anesthetic methods . Conclusion General as well as regional anesthetic methods are equally acceptable for cesarean delivery in pregnancies complicated by severe preeclampsia if steps are taken to ensure a careful approach to either method There are few consistent guidelines in choosing anesthesia for cesarean section for a parturient with placenta previa . This prospect i ve r and omized trial was organized to compare the maternal hemodynamics , blood loss and neonatal outcome of general versus epidural anesthesia for cesarean section with the diagnosis of grade 4 placenta previa . After giving informed consent , 12 patients received general anesthesia and 13 received epidural . Intraoperative blood pressures demonstrated a more stable course in the epidural group than in the general group . Blood loss did not differ significantly between the groups ( 1622 + /- 775 mL vs. 1418 + /- 996 mL ) . General anesthesia result ed in lower immediate postoperative hematocrit level ( 28.1 + /- 3.5 % vs. 32.5 + /- 5.0 % , P < 0.05 ) . The patients in the general group received a significantly larger transfusion than the epidural group ( 1.08 + /- 1.6 vs. 0.38 + /- 0.9 units , P < 0.05 ) . The Apgar scores at 1 and 5 min were similar in the two groups ( 8 [ 4 - 9 ] vs. 8 [ 7 - 9 ] and 10 [ 6 - 10 ] vs. 9 [ 9 - 10 ] , respectively ) . We concluded that epidural anesthesia is superior to general anesthesia in elective cesarean section for grade 4 placenta previa with regard to maternal hemodynamics and blood loss . There was no difference in neonatal outcome BACKGROUND The risks associated with allogeneic blood transfusion are increasingly recognized . More blood is cross-matched for moderate blood loss surgery than any other indication . The role of acute normovolemic hemodilution ( ANH ) as a blood transfusion strategy was evaluated in a prospect i ve r and omized controlled trial . STUDY DESIGN AND METHODS A total of 155 patients undergoing elective hip surgery were r and omly assigned to either " ANH " ( n = 78 ) or " st and ard transfusion " ( n = 77 ) . ANH on induction of anesthesia was to a target hemoglobin ( Hb ) level of 110 g per L with return of autologous blood on wound closure . Allogeneic blood was prescribed by an objective transfusion trigger based on an Hb level of less than 80 g per L. Transfusion requirements and postoperative complications were recorded . RESULTS Allogeneic transfusion was necessary in 22 ( 29 % ) st and ard transfusion patients and 15 ( 19 % ) ANH ( odds ratio [ OR ] , 0.6 ; 95 % CI , 0.28 - 1.3 ; p = 0.23 ) with 63 and 33 units transfused , respectively ( p = 0.1 ) . Significant postoperative complications occurred in 30 ( 38 % ) st and ard transfusion patients compared with 14 ( 18 % ) of those r and omly assigned to ANH ( OR , 0.3 ; 95 % CI , 0.14 - 0.65 ; p = 0.009 ) . The major difference between the groups was the frequency of infective complications . CONCLUSION Despite modest allogeneic transfusion requirements in hip surgery , ANH reduced postoperative complications OBJECTIVE A prospect i ve r and omized trial was organized to compare the effectiveness of general and regional anesthesia for cesarean section ( C/S ) . METHOD Three hundred and forty-one patients were r and omized into the general anesthesia group ( GA ) , epidural anesthesia group ( EA ) and spinal anesthesia group ( SA ) . The effectiveness of interest was success rate , blood loss and patient satisfaction . RESULT We found that the success rates of EA and SA were lower than GA . Success in EA should be improved by using an epidural catheter to add more local anesthetic drug instead of a single shot ; and the surgeon should allow more time for the block to work adequately . Success in SA should be improved by using bupivacaine instead of lidocaine . GA result ed in significantly more blood loss , lower postoperative hematocrit , and higher proportion of patients who had postoperative hematocrit < 30 per cent than EA and SA . The patients ' satisfaction scores were not different among the 3 techniques . This meant that , given adequate explanation and perioperative care , Thai women were satisfied with regional anesthesia . CONCLUSION Regional anesthesia is a better choice of anesthesia for C/S than general anesthesia . However , the availability of different techniques and ability to change the technique when needed were very useful and important . If GA is chosen , all safety procedures must be followed . Oxygen supplement and endotracheal intubation facilities must be available in all techniques . Guidelines of anesthesia for C/S at a national level should be agreed upon , including the type of personnel , monitoring equipment and postoperative care Summary : A prospect i ve study was conducted to compare the accuracy of visual estimation of blood loss ( EBL ) at delivery with laboratory determination of measured blood loss ( MBL ) . It showed that EBL tends to be clouded by the conventional teaching that blood loss at delivery is usually between 200 to 300 mL. Women with MBL up to 150 mL were overestimated and the best correlation was in women with MBL between 150 to 300 mL. There was a tendency to underestimate blood loss when the MBL was between 301 to 500 mL. Of the 9 women with a primary postpartum haemorrhage , only one was correctly diagnosed as such and 3 women were estimated to have blood losses of at least 500 mL but the measured blood losses were all lower . It was concluded that visual estimation of blood loss is inaccurate , especially at the extremes of MBL and that primary postpartum haemorrhage is not detected by visual estimation of blood loss , unless there are associated signs of haemodynamic instability |
12,196 | 22,371,849 | Earlier treatment with oseltamivir was generally associated with better outcomes .
Direct comparison of oral oseltamivir and inhaled zanamivir suggests no important differences in key outcomes .
Therapy with oral oseltamivir and inhaled zanamivir may provide a net benefit over no treatment of influenza . | BACKGROUND Systematic review s of r and omized , controlled trials in patients with influenza suggest a lack of evidence about the effects of antiviral therapy on several patient-important outcomes of influenza .
PURPOSE To systematic ally review observational studies for benefits and harms of oseltamivir , zanamivir , amantadine , or rimantadine in the treatment of influenza . | The risk factors for complications in patients with influenza A (H1N1)v virus infection have not been fully eluci date d. We performed an observational analysis of a prospect i ve cohort of hospitalized adults with confirmed p and emic influenza A (H1N1)v virus infection at 13 hospitals in Spain , between June 12 and November 10 , 2009 , to identify factors associated with severe disease . Severe disease was defined as the composite outcome of intensive-care unit ( ICU ) admission or in-hospital mortality . During the study period , 585 adult patients ( median age 40 years ) required hospitalization because of p and emic ( H1N1 ) 2009 . At least one comorbid condition was present in 318 ( 54.4 % ) patients . Pneumonia was diagnosed in 234 ( 43.2 % ) patients and bacterial co-infection in 45 ( 7.6 % ) . Severe disease occurred in 75 ( 12.8 % ) patients , of whom 71 required ICU admission and 13 ( 2.2 % ) died . Independent factors for severe disease were age < 50 years ( OR , 2.39 ; 95 % CI , 1.05 - 5.47 ) , chronic comorbid conditions ( OR , 2.93 ; 95 % CI , 1.41 - 6.09 ) , morbid obesity ( OR , 6.7 ; 95 % CI , 2.25 - 20.19 ) , concomitant and secondary bacterial co-infection ( OR , 2.78 ; 95 % CI , 1.11 - 7 ) and early oseltamivir therapy ( OR , 0.32 ; 95 % CI 0.16 - 0.63 ) . In conclusion , although adults hospitalized for p and emic ( H1N1 ) 2009 suffer from significant morbidity , mortality is lower than that reported in the earliest studies . Younger age , chronic comorbid conditions , morbid obesity and bacterial co-infection are independent risk factors for severe disease , whereas early oseltamivir therapy is a protective factor OBJECTIVE To compare the effectiveness of zanamivir with oseltamivir for influenza A and B. METHODS 1113 patients with influenza A or B were enrolled in the 2006 - 2007 influenza season . The duration of fever ( temperature , > or=37.5 degrees C ) and the percentage of patients afebrile at 24 and 48 h after the first dose of zanamivir or oseltamivir were calculated . Virus persistence after zanamivir therapy was also evaluated . RESULTS There were marginally significant differences between the duration of fever after the first dose of zanamivir ( 31.8+/-18.4h ) and oseltamivir ( 35.5+/-23.9h ) for influenza A ( p<0.05 ) . The duration of fever after starting zanamivir therapy ( 35.8+/-22.4h ) was significantly shorter than that of oseltamivir ( 52.7+/-31.3h ) for influenza B ( p<0.001 ) . There were no significant differences between influenza A and B in the percentage of patients afebrile at 24 or 48 h after the first inhalation of zanamivir . The reisolation rate after zanamivir therapy showed marginally significant differences between influenza A and B ( < 0.05 ) . By multiple regression analysis , therapy ( zanamivir or oseltamivir ) was the major determinant affecting the duration of fever for influenza B. CONCLUSION Zanamivir therapy is more effective than oseltamivir for the treatment of influenza B infection Background —Influenza infection has been associated with increased risk of adverse cardiac and cerebral vascular outcomes . Oseltamivir , a treatment for influenza , has been shown to decrease the severity of an influenza episode , but few data exist regarding its potentially protective effect against recurrent vascular outcomes among influenza patients with a history of vascular disease . Methods and Results —Electronic healthcare service and pharmacy records for 37 482 TRICARE beneficiaries , aged 18 and older , with a coded history of cardiovascular ( CV ) disease and a subsequent diagnosis of influenza from October 1 , 2003 , through September 30 , 2007 , were examined . Subjects were grouped according to whether they had filled a prescription for oseltamivir within 2 days of their influenza diagnosis . The incidence of recurrent CV events within 30 days after the influenza diagnosis among oseltavmivir-treated and untreated subjects was 8.5 % and 21.2 % , respectively ( P<0.005 ) . Subject age was a persistent and significant contributor to the likelihood of recurrent CV outcomes . After controlling for the differences in demographics among treated and untreated cohorts using a propensity-scored logistic regression model , a statistically significant protective effect was associated with oseltamivir treatment ( odds ratio , 0.417 ; 95 % CI , 0.349 to 0.498 ) . Conclusions —Our findings suggests that oseltamivir treatment for influenza is associated with significant decrease in the risk of recurrent CV events in subjects with a history of CV disease . These findings merit confirmation in further prospect i ve and controlled studies . Meanwhile , in patients with CV disease , strict adherence with current practice guidelines for prevention and treatment of influenza is recommended BACKGROUND In April 2009 a novel influenza A virus ( AH1N1v ) of swine origin ( swine flu ) emerged , spreading rapidly and achieving p and emic status in June 2009 . Pregnant women were identified as being at high risk of severe influenza-related complications and as a priority group for vaccination against AH1N1v . Limited information was available about the maternal and fetal risks of AH1N1v infection or of antiviral drug or AH1N1v vaccine use in pregnancy . OBJECTIVES To assess rates of and risk factors for adverse outcomes following AH1N1v infection in pregnancy and to assess the adverse effects of the antiviral drugs and vaccines used in prevention and management . METHODS Prospect i ve national cohort studies were conducted to identify pregnant women who were ( 1 ) suspected to be infected with AH1N1v or being treated with antiviral medication in primary care ; ( 2 ) vaccinated against AH1N1v ; and ( 3 ) admitted to hospital with confirmed AH1N1v . Characteristics of women with influenza-like illness ( ILI ) in primary care were compared with those of women without symptoms accepting or declining immunisation . Characteristics of women admitted to hospital with confirmed AH1N1v infection in pregnancy were compared with a historical cohort of over 1200 women giving birth in the UK who were uninfected with AH1N1v . Outcomes examined in hospitalised women included maternal death , admission to an intensive care unit , perinatal mortality and preterm birth . Risk factors for hospital and intensive care unit admission were examined in a full regression model . RESULTS The weekly incidence of ILI among pregnant women averaged 51/100,000 over the study period . Antiviral drugs were offered to 4.8 % [ 95 % confidence interval ( CI ) 4.0 % to 5.9 % ] and vaccination to 64.8 % ( 95 % CI 64.7 % to 68.9 % ) of registered pregnant women . Ninety pregnant women with ILI presenting in primary care were reported to the research team , 55 of whom were prescribed antiviral drugs and in 42 ( 76 % ) cases this was within 2 days of symptom onset . After comparison with 1329 uninfected pregnant women offered vaccination , pre-existing asthma was the only maternal factor identified as increasing risk of ILI presentation [ adjusted odds ratio ( OR ) 2.0 , 95 % CI 1.0 to 3.9 ] . Maternal obesity and smoking during pregnancy were also associated with hospital admission with AH1N1v infection . Overall , 241 pregnant women were admitted to hospital with laboratory-confirmed AH1N1v infection . Eighty-three per cent of these women were treated with antiviral agents , but only 6 % received antiviral treatment before hospital admission . Treatment within 2 days of symptom onset was associated with an 84 % reduction in the odds of admission to an intensive therapy unit ( OR 0.16 , 95 % CI 0.08 to 0.34 ) . Women admitted to hospital with AH1N1v infection were more likely to deliver preterm ; a three times increased risk was suggested compared with an uninfected population cohort ( OR 3.1 , 95 % CI 2.1 to 4.5 ) . CONCLUSIONS Earlier treatment with antiviral agents is associated with improved outcomes for pregnant women and further actions are needed in future p and emics to ensure that antiviral agents and vaccines are provided promptly to pregnant women , particularly in the primary care setting . Further research is needed on longer-term outcomes for infants exposed to AH1N1v influenza , antiviral drugs or vaccines during pregnancy Background The aim of this study was to investigate factors affecting clinical outcomes of adults hospitalised with severe seasonal influenza . Methods A prospect i ve , observational cohort study was conducted over 24 months ( 2007–2008 ) in two acute , general hospitals . Consecutive , hospitalised adult patients were recruited and followed once their laboratory diagnosis of influenza A/B was established ( based on viral antigen detection and virus isolation from nasopharyngeal aspirates collected per protocol ) . Outcomes studied included in-hospital death , length of stay and duration of oxygen therapy . Factors affecting outcomes were analysed using multivariate Cox proportional hazards models . Sequencing analysis on the neuraminidase gene was performed for available H1N1 isolates . Results 754 patients were studied ( influenza A , n=539 ; > 75 % H3N2 ) . Their mean age was 70±18 years ; co-morbidities and serious complications were common ( 61–77 % ) . Supplemental oxygen and ventilatory support was required in 401 ( 53.2 % ) and 41 ( 5.4 % ) patients , respectively . 39 ( 5.2 % ) patients died ; pneumonia , respiratory failure and sepsis were the causes . 395 ( 52 % ) patients received antiviral ( oseltamivir ) treatment . Omission of antiviral treatment was associated with delayed presentation or negative antigen detection results . The mortality rate was 4.56 and 7.42 per 1000 patient-days in the treated and untreated patients , respectively ; among those with co-morbidities , it was 5.62 and 11.64 per 1000 patient-days , respectively . In multivariate analysis , antiviral use was associated with reduced risk of death ( adjusted HR ( aHR ) 0.27 ( 95 % CI 0.13 to 0.55 ) ; p<0.001 ) . Improved survival was observed with treatment started within 4 days from onset . Earlier hospital discharge ( aHR 1.28 ( 95 % CI 1.04 to 1.57 ) ; p=0.019 ) and faster discontinuation of oxygen therapy ( aHR 1.30 ( 95 % CI 1.01 to 1.69 ) ; p=0.043 ) was associated with early treatment within 2 days . Few ( n=15 ) H1N1 isolates in this cohort had the H275Y mutation . Conclusions Antiviral treatment for severe influenza is associated with reduced mortality and improved clinical outcomes Oseltamivir has been used for treatment of influenza A and B infections , but recent reports documented that it was less active against the latter . We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan . Among 1,848 patients screened , 299 influenza A and 209 influenza B patients were administered oseltamivir ( treated groups ) , and 28 influenza A and 66 influenza B patients were assigned as non-treated groups . The duration of fever , defined as period when patients had the maximum temperature higher than 37.5 degrees C in three-time measurements in a day after the clinic visit , was evaluated among the four groups . In uni-variate analysis , the duration of fever was shorter for treated group than non-treated for influenza A ( 1.8 + /- 0.9 days vs 2.6 + /- 1.3 days , p < 0.01 ) , but it was not significant for influenza B ( 2.4 + /- 1.3 days vs 2.8 + /- 1.2 days , p = 0.9 ) . The fever duration was longer in treated influenza B than A patients ( p < 0.01 ) . Multi-variate analysis indicated younger age ( < 6 years old ) and higher body temperature at the clinic visit prolonged the duration of fever . Adjusted average duration of fever indicated that oseltamivir was effective for both types , but more effective on influenza A , and the benefit increased for younger children . Our data provide evidence that oseltamivir is beneficial for influenza infections , but the effectiveness is differed by type and age BACKGROUND To compare the effectiveness of oseltamivir for treatment of influenza A and influenza B , we conducted a prospect i ve , multicenter study of the 2003 - 2004 and 2004 - 2005 influenza seasons . The study included 3351 patients in whom influenza had been diagnosed by use of an antigen detection test kit . METHODS Oseltamivir was administered to 1818 patients with influenza A and 1485 patients with influenza B. No anti-influenza drugs were administered to 21 patients with influenza A or to 27 patients with influenza B. Patients receiving oseltamivir therapy were divided into 4 groups according to the time between the onset of fever ( temperature , > or = 37.5 degrees C ) and administration of the first dose of oseltamivir ( 0 - 12 h , 13 - 24 h , 25 - 36 h , and 37 - 48 h ) . The patients were also divided into 4 subgroups on the basis of age ( 0 - 6 years , 7 - 15 years , 16 - 64 years , and > 64 years ) . Virus isolation was performed after completion of oseltamivir therapy for 44 patients with influenza A and 31 patients with influenza B. RESULTS The duration of fever was significantly shorter for patients with influenza A and B who were treated with oseltamivir than for patients who were not treated with an anti-influenza drug ( P<.001 for both ) . The time until the patient became afebrile after the initial administration of oseltamivir and the duration of fever were significantly longer for patients with influenza B than for patients with influenza A for the 0 - 12 h , 13 - 24 h , 25 - 36 h , and 37 - 48 h groups ( P<.001 ) and for all age groups ( P<.001 ) . After 4 - 6 days of oseltamivir therapy , the influenza B virus reisolation rate ( 51.6 % ) was significantly higher than the influenza A virus reisolation rate ( 15.9 % ) ( P<.001 ) . CONCLUSION Oseltamivir is less effective for influenza B than for influenza A with regard to duration of fever and virus persistence , irrespective of patient age or the timing of administration of the first dose Summary : Respiratory viruses ( RVs ) frequently cause severe respiratory disease in bone marrrow transplant ( BMT ) recipients . To evaluate the frequency of RV , nasal washes were collected year-round from BMT recipients with symptoms of upper respiratory tract infection ( URI ) . Direct immunofluorescence assay was performed for respiratory syncytial virus ( RSV ) , influenza ( Flu ) A and B , adenovirus and parainfluenza ( Paraflu ) virus . Patients with RSV pneumonia or with upper RSV infection , but considered at high risk for developing RSV pneumonia received aerosolized ribavirin . Oseltamivir was given to patients with influenza . A total of 179 patients had 392 episodes of URI . In all , 68 ( 38 % ) tested positive : RSV was detected in 18 patients ( 26.4 % ) , Flu B in 17 ( 25 % ) , Flu A in 11 ( 16.2 % ) and Paraflu in 7 ( 10.3 % ) . A total of 14 patients ( 20.6 % ) had multiple RV infections or coinfection . RSV pneumonia developed in 55.5 % of the patients with RSV-URI . One of the 15 patients ( 6.6 % ) with RSV pneumonia died . Influenza pneumonia was diagnosed in three patients ( 7.3 % ) . RSV and influenza infections peaked in fall – winter and winter – spring months , respectively . We observed decreased rates of influenza and parainfluenza pneumonia and low mortality because of RSV pneumonia . The role of antiviral interventions such as aerosolized ribavirin and new neuraminidase inhibitors remains to be defined in r and omized trials Abstract Background The goal of this study was to characterize viral loads and factors affecting viral clearance in persons with severe influenza Methods This was a 1-year prospect i ve , observational study involving consecutive adults hospitalized with influenza . Nasal and throat swabs were collected at presentation , then daily until 1 week after symptom onset . Real-time reverse-transcriptase polymerase chain reaction to determine viral RNA concentration and virus isolation were performed . Viral RNA concentration was analyzed using multiple linear or logistic regressions or mixed-effect models Results One hundred forty-seven in patients with influenza A ( H3N2 ) infection were studied ( mean age ± st and ard deviation , 72±16 years ) . Viral RNA concentration at presentation positively correlated with symptom scores and was significantly higher than that among time-matched out patients ( control subjects ) . Patients with major comorbidities had high viral RNA concentration even when presenting > 2 days after symptom onset ( mean ± st and ard deviation , 5.06±1.85 vs 3.62±2.13 log10 copies/mL ; P=.005 ; β , + 0.86 [ 95 % confidence interval , + 0.03 to + 1.68 ] ) . Viral RNA concentration demonstrated a nonlinear decrease with time ; 26 % of oseltamivir-treated and 57 % of untreated patients had RNA detected at 1 week after symptom onset . Oseltamivir started on or before symptom day 4 was independently associated with an accelerated decrease in viral RNA concentration ( mean β [ st and ard error ] , −1.19 [ 0.43 ] and −0.68 [ 0.33 ] log10 copies/mL for patients treated on day 1 and days 2–3 , respectively ; P<.05 ) and viral RNA clearance at 1 week ( odds ratio , 0.10 [ 95 % confidence interval , 0.03–0.35 ] and 0.30 [ 0.10–0.90 ] for patients treated on day 1–2 and day 3–4 , respectively ) . Conversely , major comorbidities and systemic corticosteroid use for asthma or chronic obstructive pulmonary disease exacerbations were associated with slower viral clearance . Viral RNA clearance was associated with a shorter hospital stay ( 7.0 vs 13.5 days ; P=.001 ) Conclusion Patients hospitalized with severe influenza have more active and prolonged viral replication . Weakened host defenses slow viral clearance , whereas antivirals started within the first 4 days of illness enhance viral BACKGROUND We conducted a prospect i ve cohort study to assess the impact of antiviral therapy on outcomes of patients hospitalized with influenza in southern Ontario , Canada . METHODS Patients admitted to Toronto Invasive Bacterial Diseases Network hospitals with laboratory-confirmed influenza from 1 January 2005 through 31 May 2006 were enrolled in the study . Demographic and medical data were collected by patient and physician interview and chart review . The main outcome evaluated was death within 15 days after symptom onset . RESULTS Data were available for 512 of 541 eligible patients . There were 185 children ( < 15 years of age ) , none of whom died and none of whom were treated with antiviral drugs . The median age of the 327 adults was 77 years ( range , 15 - 98 years ) , 166 ( 51 % ) were male , 245 ( 75 % ) had a chronic underlying illness , and 216 ( 71 % ) had been vaccinated against influenza . Of the 327 adult patients , 184 ( 59 % ) presented to the emergency department within 48 h after symptom onset , 52 ( 16 % ) required intensive care unit admission , and 27 ( 8.3 % ) died within 15 days after symptom onset . Most patients ( 292 patients ; 89 % ) received antibacterial therapy ; 106 ( 32 % ) were prescribed antiviral drugs . Treatment with antiviral drugs active against influenza was associated with a significant reduction in mortality ( odds ratio , 0.21 ; 95 % confidence interval , 0.06 - 0.80 ; n=100 , 260 ) . There was no apparent impact of antiviral therapy on length of stay in survivors . CONCLUSIONS There is a significant burden of illness attributable to influenza in this highly vaccinated population . Treatment with antiviral drugs was associated with a significant reduction in mortality From January 2001 to July 2002 , we investigated the duration of fever , the duration of hospitalization , the frequency of antipyretic use , and other clinical symptoms of 162 in patients with influenza A virus infection , and compared them with oseltamivir-treated , amantadine-treated , and untreated groups . The duration of fever and the duration of hospitalization treated were significantly shortened in the oseltamivir-treated group than in the amantadine-treated group and untreated group . There was no difference in the duration of fever between patients treated by oseltamivir at 2 mg/kg/day and those at 4 mg/kg/day . The frequency of antipyretic use was lower in the oseltamivir-treated group than in the other group . No difference was observed in the duration of fever and the frequency of antipyretic use between patients treated by oseltamivir with antibiotics and those by oseltamivir alone . The complications such as vomiting , abdominal pain , irritability were observed in 9 % of patients treated by oseltamivir . But those symptoms were not serious , and the rate of complications in the oseltamivir-treated group was lower than that in untreated group . In conclusion , oseltamivir is safe and effective in the treatment of influenza virus infection in children , and it may reduce the amount of antibiotics and antipyretic use BACKGROUND To evaluate the effectiveness of oseltamivir and amantadine for the treatment of influenza with respect to various clinical factors , a prospect i ve multicenter study of the influenza season of 2002 - 2003 was done with 2163 patients whose condition was diagnosed by an antigen-detection test kit . METHODS Oseltamivir was administered to 803 patients with influenza A ( A+Os group ) and 684 patients with influenza B ( B+Os group ) . Amantadine was administered to 676 patients with influenza A ( A+Am group ) . RESULTS For each group , the duration of fever ( i.e. , body temperature , > or = 37.5 degrees C ) was significantly shorter in patients who received the drug within 12 h after the onset of symptoms than in patients who received the drug > 12 h after the onset . For all 3 groups , the duration of fever was shorter in patients with a highest temperature < 39 degrees C than in patients with temperatures > or = 39 degrees C. The duration of fever was significantly longer for the B+Os group than for the A+Os group . Multiple regression analysis found that the type of influenza , the highest body temperature , and the time between the onset of symptoms and the start of treatment are independent factor that influence the duration of fever . CONCLUSIONS Early administration increases the benefit of anti-influenza drugs -- not only the benefit of oseltamivir treatment for influenza A , but also the benefit of amantadine treatment for influenza A and oseltamivir treatment for influenza B. Oseltamivir may be less effective as a treatment for influenza B than for influenza A. A highest body temperature of > or = 39 degrees C was an indicator of a longer duration of fever In a retrospective survey , 487 research projects approved by the Central Oxford Research Ethics Committee between 1984 and 1987 , were studied for evidence of publication bias . As of May , 1990 , 285 of the studies had been analysed by the investigators , and 52 % of these had been published . Studies with statistically significant results were more likely to be published than those finding no difference between the study groups ( adjusted odds ratio [ OR ] 2.32 ; 95 % confidence interval [ Cl ] 1.25 - 4.28 ) . Studies with significant results were also more likely to lead to a greater number of publications and presentations and to be published in journals with a high citation impact factor . An increased likelihood of publication was also associated with a high rating by the investigator of the importance of the study results , and with increasing sample size . The tendency towards publication bias was greater with observational and laboratory-based experimental studies ( OR = 3.79 ; 95 % Cl = 1.47 - 9.76 ) than with r and omised clinical trials ( OR = 0.84 ; 95 % Cl = 0.34 - 2.09 ) . We have confirmed the presence of publication bias in a cohort of clinical research studies . These findings suggest that conclusions based only on a review of published data should be interpreted cautiously , especially for observational studies . Improved strategies are needed to identify the results of unpublished as well as published studies BACKGROUND Data on the clinical effectiveness of oseltamivir in patients with p and emic 2009 influenza A(H1N1 ) ( A[H1N1 ] ) virus infection are scarce . We aim ed to determine the effect of timing of oseltamivir administration on outcomes in hospitalized adults with A(H1N1 ) . METHODS Observational analysis of a prospect i ve cohort of adults hospitalized with laboratory-confirmed A(H1N1 ) was performed at 13 Spanish hospitals . Time from onset of symptoms to oseltamivir administration was the independent variable . Outcomes were duration of fever , hospital length of stay ( LOS ) , need for mechanical ventilation , and mortality during hospitalization . Multivariate logistic regression was used to describe the association between the independent variable and the outcomes . RESULTS Five hundred thirty-eight hospitalized patients with A(H1N1 ) were studied . The median time from onset of symptoms to oseltamivir administration was 3 days ( interquartile range [ IQR ] , 2 - 5 days ) . With regard to outcomes , the median duration of fever was 2 days ( IQR , 1 - 3 days ) , the median LOS was 5 days ( IQR , 3 - 8 days ) , 49 patients ( 9.1 % ) underwent mechanical ventilation , and 11 patients ( 2 % ) died during hospitalization . In univariate analysis , prolonged duration of fever ( above the median ) , prolonged LOS ( above the median ) , need for mechanical ventilation , and mortality all increased with time to oseltamivir administration ( χ(2 ) test for trend P = .001 , P ≤ .001 , P = .008 , and P = .001 , respectively ) . After adjustment for confounding factors , time from onset of symptoms to oseltamivir administration ( + 1-day increase ) was associated with a prolonged duration of fever ( OR , 1.10 ; 95 % CI , 1.02 - 1.19 ) , prolonged LOS ( OR , 1.07 ; 95 % CI , 1.00 - 1.15 ) , and higher mortality ( OR , 1.20 ; 95 % CI , 1.06 - 1.35 ) . CONCLUSIONS Timely oseltamivir administration has a beneficial effect on outcomes in hospitalized adults with A(H1N1 ) , even in those who are admitted beyond 48 h after onset of symptoms |
12,197 | 27,956,247 | There is some evidence to support the use of computerised insulin dosing calculators for insulin infusion management within critical care environments | OBJECTIVES To investigate the effectiveness of computerised insulin dosing calculators for the management of continuous insulin infusions in adult patients who underwent cardiac surgery . | People with diabetes are more likely to be hospitalized and to have longer duration s of hospital stay than those without diabetes . A recent survey estimated that 22 % of all hospital inpatient days were incurred by people with diabetes and that hospital inpatient care accounted for half of the 174 billion USD total U.S. medical expenditures for this disease ( 1 ) . These findings are due , in part , to the continued expansion of the worldwide epidemic of type 2 diabetes . In the U.S. alone , there are ∼1.6 million new cases of diabetes each year , with an over all prevalence of 23.6 million people ( 7.8 % of the population , with one-fourth of the cases remaining undiagnosed ) . An additional 57 million American adults are at high risk for type 2 diabetes ( 2 ) . Although the costs of illness-related stress hyperglycemia are not known , they are likely to be considerable in light of the poor prognosis of such patients ( 3–6 ) . There is substantial observational evidence linking hyperglycemia in hospitalized patients ( with or without diabetes ) to poor outcomes . Cohort studies as well as a few early r and omized controlled trials ( RCTs ) have suggested that intensive treatment of hyperglycemia improved hospital outcomes ( 5–8 ) . In 2004 , this evidence led the American College of Endocrinology ( ACE ) and the American Association of Clinical Endocrinologists ( AACE ) , in collaboration with the American Diabetes Association ( ADA ) and other medical organizations , to develop recommendations for treatment of inpatient hyperglycemia ( 9 ) . In 2005 , the ADA added recommendations for treatment of hyperglycemia in the hospitalto itsannual St and ards of Medical Care ( 10 ) . Recommendations from the ACE and the ADA generally endorsed tight glycemic control in critical care units . For patients in general medical and surgical units , where RCT evidence regarding treatment targets was lacking , glycemic goals similar to those advised for out patients were advocated ( 9 , Type 2 diabetes is associated with altered immune and hemostatic responses . We investigated the selective effects of hyperglycemia and hyperinsulinemia on innate immune , coagulation , and fibrinolytic responses during systemic inflammation . Twenty-four healthy humans were studied for 8 hours during clamp experiments in which either plasma glucose , insulin , both , or none was increased , depending on r and omization . Target plasma concentrations were 5 versus 12 mM for glucose , and 100 versus 400 pmol/L for insulin . After 3 hours , 4 ng/kg Escherichia coli endotoxin was injected intravenously to induce a systemic inflammatory and procoagulant response . Endotoxin administration induced cytokine release , activation of neutrophils , endothelium and coagulation , and inhibition of fibrinolysis . Hyperglycemia reduced neutrophil degranulation ( plasma elastase levels , P < .001 ) and exaggerated coagulation ( plasma concentrations of thrombin-antithrombin complexes and soluble tissue factor , both P < .001 ) . Hyperinsulinemia attenuated fibrinolytic activity due to elevated plasminogen activator-inhibitor-1 levels ( P < .001 ) . Endothelial cell activation markers and cytokine concentrations did not differ between clamps . We conclude that in humans with systemic inflammation induced by intravenous endotoxin administration hyperglycemia impairs neutrophil degranulation and potentiates coagulation , whereas hyperinsulinemia inhibits fibrinolysis . These data suggest that type 2 diabetes patients may be especially vulnerable to prothrombotic events during inflammatory states BACKGROUND Glycemic control is important to patients ' outcomes . However , the process of maintaining glycemic control is risk laden and labor intensive for nurses . OBJECTIVES To examine the effects of using a computerized insulin dose calculator to facilitate management of glycemic control for critically ill cardiac patients . METHODS A prospect i ve r and omized controlled trial was conducted with a sample of 300 intensive care patients , 141 r and omized to the calculator group and 159 in the control ( paper protocol ) group . A convenience sample of 44 intensive care nurses responded to a nurse satisfaction survey . RESULTS A significantly higher percentage of glucose measurements were in the target range in the calculator group than in the control group ( 70.4 % [ SD , 15.2 % ] vs 61.6 % [ SD , 17.9 % ] , Z = -4.423 , P < .001 ) , and glucose variance was significantly less in the calculator group ( 35.5 [ SD , 18.3 ] mg/dL vs 42.3 [ SD , 21.2 ] mg/dL , Z = -3.845 , P < .001 ) . Fewer hypoglycemic events occurred in the calculator group ( 7 vs 18 ) , although this difference was not statistically significant . Nurse satisfaction was higher for the calculator group than for the control group ( 8.4 [ SD , 1.4 ] vs 4.8 [ SD , 2.4 ] , Z = -5.055 , P < .001 ) . Nurses ' deviation from the protocol was also less in the calculator group than in the control group . CONCLUSIONS Management of glycemic control and nurse satisfaction were improved with use of the dose calculator . Improving nurses ' processes of care may improve nurses ' use of time and patient care overall . Studies with larger sample sizes over time are needed to determine these relationships BACKGROUND Intensive glycemic control has been associated with reduced morbidity and mortality in critically ill patients . Web-based , patient-specific insulin nomograms may facilitate improved glucose control . OBJECTIVE To compare 2 algorithms for individualizing insulin infusion therapy ( a web-based system [ Glucomm and er method ] and a st and ard paper-based nomogram ) in a cardiovascular surgery intensive care unit ( ICU ) . METHODS In this prospect i ve , before-after cohort study , measures of glycemic control for 50 patients receiving insulin according to the Glucomm and er system were compared with a control group ( n = 50 ) who received insulin according to the st and ard paper-based nomogram used in the cardiovascular surgery ICU . RESULTS There was no significant difference between the 2 groups with respect to time to target blood glucose ( 5.1 - 8.0 mmol/L ) , percentage of time within the target range , or mean amplitude of glucose excursion . Patients in the intervention group spent less time above the target range ( p = 0.007 ) and more time below the target range ( p < 0.001 ) , and the mean glucose was lower in this group compared with the control group ( 7.9 versus 8.6 mmol/L , p = 0.002 ) . The percentage of blood glucose measurements below 4 mmol/L was higher in the intervention group than in the control group ( 3.7 % versus 1.4 % , p = 0.003 ) . Satisfaction surveys revealed that the program was well accepted by the nursing staff in the cardiovascular surgery ICU . CONCLUSIONS A web-based insulin nomogram was an easy-to-use instrument for achieving tighter glucose control for patients in the cardiovascular surgery ICU . Use of the Glucomm and er system led to lower mean blood glucose but an increase in episodes of hypoglycemia BACKGROUND : In the setting of protocol ized glycemic control , the relationship between postoperative glycemic variability on major adverse events ( MAEs ) after cardiac surgery is unknown for patients with increased preoperative hemoglobin A1C ( HbA1C > 6.5 % ) . In this study , we sought to establish ( a ) whether postoperative glycemic variability is associated with MAEs after CABG surgery and ( b ) whether preoperative HbA1C could identify patients at increased risk of postoperative glycemic variability . METHODS : Patients undergoing coronary artery bypass grafting with or without valvular surgery from January 2008 to May 2011 were enrolled in this prospect i ve , single-center , observational cohort study . Demographic , intraoperative , and postoperative outcome data were obtained from institutional data collected for the Society of Thoracic Surgery ( STS ) data base . The primary outcome , MAE was a composite of in-hospital death , myocardial infa rct ion ( MI ) , reoperations , sternal infection , cardiac tamponade , pneumonia , stroke , or renal failure . Glycemic variability in the postoperative period was assessed by the coefficient of variation ( CV ) . CV was used as quartiles for the multivariate logistic regression . Variable selection in multivariable modeling was based on clinical and statistical significance and was performed in a hierarchical fashion . RESULTS : Of the 1461 patients enrolled , 9.8 % had an MAE . Based on the established target of HbA1C < 6.5 % for the diagnosis of diabetes mellitus , we considered HbA1C as a binary variable ( < 6.5 % and ≥6.5 % ) in our primary analysis . Multivariate logistic regression analyses for the preoperative variables only revealed that preoperative HbA1C ( odds ratio [ OR ] , 1.6 ; 95 % confidence interval [ CI ] , 1.1–2.3 ; P = 0.02 ) , history of MI ( OR , 1.9 ; 95 % CI , 1.3–2.8 ; P = 0.001 ) , and STS risk score per quartile ( OR , 1.7 ; 95 % CI , 1.4–2.1 ; P < 0.001 ) were associated with MAEs . When postoperative variables were included in the analyses , postoperative glycemic variability ( CV per quartile ) in the intensive care unit ( OR , 1.3 ; 95 % CI , 1.1–1.5 ; P = 0.03 ) , mean glucose levels averaged over the first 4 postoperative hours ( OR , 1.2 ; 95 % CI , 1.0–1.4 ; P = 0.03 ) , history of MI ( OR , 1.8 ; 95 % CI , 1.2–2.6 ; P = 0.004 ) , and STS risk score per quartile ( OR , 1.6 ; 95 % CI , 1.3–2.0 ; P < 0.001 ) were associated with MAEs . Glycemic variability as assessed by CV was increased postoperatively in patients with preoperative HbA1C ≥6.5 % ( 0.20 ± 0.09 vs 0.16 ± 0.07 , P < 0.001 ) . CONCLUSIONS : Postoperative glycemic variability is associated with MAEs after cardiac surgery . Glycemic variability is only measured when the patient leaves the intensive care unit , and there is no opportunity to intervene earlier . Preoperative HbA1C identifies risk for postoperative glycemic variability and may provide a more rational guide for targeting measures to reduce variability OBJECTIVE We performed a r and omized trial to compare three insulin-titration protocol s for tight glycemic control ( TGC ) in a surgical intensive care unit : an absolute glucose ( Matias ) protocol , a relative glucose change ( Bath ) protocol , and an enhanced model predictive control ( eMPC ) algorithm . RESEARCH DESIGN AND METHODS A total of 120 consecutive patients after cardiac surgery were r and omly assigned to the three protocol s with a target glycemia range from 4.4 to 6.1 mmol/l . Intravenous insulin was administered continuously or in combination with insulin boluses ( Matias protocol ) . Blood glucose was measured in 1- to 4-h intervals as requested by the protocol s. RESULTS The eMPC algorithm gave the best performance as assessed by time to target ( 8.8 ± 2.2 vs. 10.9 ± 1.0 vs. 12.3 ± 1.9 h ; eMPC vs. Matias vs. Bath , respectively ; P < 0.05 ) , average blood glucose after reaching the target ( 5.2 ± 0.1 vs. 6.2 ± 0.1 vs. 5.8 ± 0.1 mmol/l ; P < 0.01 ) , time in target ( 62.8 ± 4.4 vs. 48.4 ± 3.28 vs. 55.5 ± 3.2 % ; P < 0.05 ) , time in hyperglycemia > 8.3 mmol/l ( 1.3 ± 1.2 vs. 12.8 ± 2.2 vs. 6.5 ± 2.0 % ; P < 0.05 ) , and sampling interval ( 2.3 ± 0.1 vs. 2.1 ± 0.1 vs. 1.8 ± 0.1 h ; P < 0.05 ) . However , time in hypoglycemia risk range ( 2.9–4.3 mmol/l ) in the eMPC group was the longest ( 22.2 ± 1.9 vs. 10.9 ± 1.5 vs. 13.1 ± 1.6 ; P < 0.05 ) . No severe hypoglycemic episode ( < 2.3 mmol/l ) occurred in the eMPC group compared with one in the Matias group and two in the Bath group . CONCLUSIONS The eMPC algorithm provided the best TGC without increasing the risk of severe hypoglycemia while requiring the fewest glucose measurements . Overall , all protocol s were safe and effective in the maintenance of TGC in cardiac surgery patients OBJECTIVE To evaluate a fully automated algorithm for the establishment of tight glycemic control in critically ill patients and to compare the results with different routine glucose management protocol s of three intensive care units ( ICUs ) across Europe ( Graz , Prague , and London ) . RESEARCH DESIGN AND METHODS Sixty patients undergoing cardiac surgery ( age 67 + /- 9 years , BMI 27.7 + /- 4.9 kg/m2 , 17 women ) with postsurgery blood glucose levels > 120 mg/dl ( 6.7 mmol/l ) were investigated in three different ICUs ( 20 per center ) . Patients were r and omized to either blood glucose management ( target range 80 - 110 mg/dl [ 4.4 - 6.1 mmol/l ] ) by the fully automated model predictive control ( MPC ) algorithm ( n = 30 , 10 per center ) or implemented routine glucose management protocol s ( n = 30 , 10 per center ) . In all patients , arterial glucose was measured hourly to describe the glucose profile until the end of the ICU stay but for a maximum period of 48 h. RESULTS Compared with routine protocol s , MPC treatment result ed in a significantly higher percentage of time within the target glycemic range ( % median [ min-max ] : 52 [ 17 - 92 ] vs. 19 [ 0 - 71 ] ) over 0 - 24 h ( P < 0.01 ) . Improved glycemic control with MPC treatment was confirmed in patients remaining in the ICU for 48 h ( 0 - 24 h : 50 [ 17 - 71 ] vs. 21 [ 4 - 67 ] , P < 0.05 , and 24 - 48 h : 65 [ 38 - 96 ] vs. 25 [ 8 - 79 ] , P < 0.05 , for MPC [ n = 16 ] vs. routine protocol [ n = 13 ] , respectively ) . Two hypoglycemic events ( < 54 mg/dl [ 3.0 mmol/l ] ) were observed with routine protocol treatment . No hypoglycemic event occurred with MPC . CONCLUSIONS The data suggest that the MPC algorithm is safe and effective in controlling glycemia in critically ill postsurgery patients Humans have a limited ability to incorporate information in decision making ( 1 , 2 ) . Our short-term memory can simultaneously retain and therefore optimally utilizeonly four to seven data constructs ; attempts to use larger amounts of information at one time lead to ineffective decision making ( 3 ) . This limitation st and s in striking contrast to the hundreds of variables encountered by clinicians in the clinical environment . The mismatch between human limitation and excess information almost certainly contributes to unnecessary variation in clinical practice ( 4 - 9 ) , clinical error ( 10 - 22 ) , and poor compliance with guidelines ( 23 - 27 ) . In this paper , I consider the problems created by this mismatch and describe a computer-based decision-support system that successfully combines rules based on credible evidence with specific data from individual patients . I also review key social , psychological , and administrative elements that have made development of this system possible . Variation and the St and ardization of Practice Variation in clinical practice persists even when guidelines based on reputable evidence are available ( 28 , 29 ) . Harm can result when clinicians do not comply with st and ard practice ( 9 , 30 , 31 ) . Of note , much of current clinical practice has not yet been shown to produce more good than harm ( 18 , 32 - 34 ) . Widespread distribution of evidence -based guidelines ( 35 , 36 ) and education programs ( 24 , 37 - 40 ) have had only a limited effect on low clinician compliance , and patient compliance ( 41 ) and hospital compliance ( 42 ) are almost as low . Unaided human decision makers do not possess the consistency of behavior or the accuracy of perception necessary for the consistent delivery of recommended therapies ( 10 , 43 - 48 ) . St and ardization of clinical decisions is needed not only for clinical practice but also for rigorous clinical research ( 49 ) . Many interventions of clinical value have relatively small effects , with odds ratios of 3.0 or less ( 50 ) . Systematic ally conducted clinical trials are necessary to recognize these small effects and to identify ineffective clinical care elements ( 50 , 51 ) . Without explicit methods , however , the fundamental scientific requirement of replicability of results ( 48 , 49 ) can not be achieved . An explicit method contains enough detail to generate specific instructions ( patient-specific orders ) without requiring judgments by a clinician . It is driven by patient data and generates the same instruction for a given set of input data . Any form of guideline or protocol can theoretically contain enough detail to constitute an explicit method . In practice , however , paper-based versions of any protocol s but the simplest ones ( for example , vaccination schedules or treatment of hypokalemia in a patient receiving digitalis and diuretics ) can not be made explicit and therefore remain dependent on clinician judgment . The need to st and ardize decisions provides a counterpoint to the equally compelling need to deliver individualized , patient-specific treatment . Unexpectedly , the discussed computerized protocol s , which are explicit , detailed , and patient data -driven , can simultaneously achieve st and ardization of clinical decision making and individualization of patient therapy ( 52 ) . Clinical care ( the treatment a patient receives ) is determined by clinical caregivers ' decisions and by each patient 's individualized expression of his or her illness ( 52 ) . Consider an explicit method for mechanical ventilationfor example , a computerized protocol that is used to st and ardize clinical decisions for two patients . The treatment given to one of the patients , who responded to positive end-expiratory pressure , would differ from that given to the other patient , who did not ; treatments would differ even though the same explicit decision-making rules were used to st and ardize clinical decisions for both patients . The clinical care delivered to patients through computerized protocol instructions is therefore individualized ( patient-specific ) although decision making is st and ardized . Patient-specific care contrasts with time-driven decision-support tools , such as a clinical pathway that requires extubation within 36 hours and discharge from the hospital within a specified time . Unlike explicit methods driven by patient data ( 25 , 53 - 58 ) , time-driven tools raise legitimate concerns about patient-invariant ( cookbook ) care . One of the most attractive features of the use of point-of-care computerized protocol s is their ability to individualize patient care while st and ardizing clinical decisions with an explicit method . The LDS Hospital Experience Two computerized protocol s developed at LDS Hospital , Salt Lake City , Utah , form the case studies for this discussion . The first protocol st and ardizes bedside decisions for mechanical ventilation of patients with the acute respiratory distress syndrome ( ARDS ) . These decision-support tools were initially developed for a r and omized clinical trial of extracorporeal carbon dioxide removal in patients with ARDS ( 53 ) . The tools were subsequently exported to 10 other hospitals ( in 8 cities in 7 states ) uninvolved in the development and were then evaluated in a r and omized clinical trial of mechanical ventilation in patients with ARDS ( 54 ) . The second protocol st and ardizes bedside clinical decisions for intravenous fluid and hemodynamic support . These protocol s were recently developed for a projected r and omized clinical trial of pulmonary artery catheters by the NIH/NHLBI ( National Institutes of Health/National Heart , Lung , and Blood Institute ) ARDS Clinical Network ( 55 ) . Varieties of Decision Support Guidelines and protocol s can effectively support clinical decision making ( 56 ) and can favorably influence clinician performance and patient outcome ( 28 , 57 - 59 ) . These decision-support tools have been functionally categorized as reminders , as consultants , or as educational ( 60 ) . Thous and s of decision-support tools with different names , focuses , and outputs are currently available to clinical practitioners . However , they often lack specific instructions for many of the scenarios encountered in clinical practice ( Table 1 ) . Most guidelines and algorithms ( including guidelines generated by the Agency for Healthcare Research and Quality ) are useful only in a conceptual sense ( 61 - 67 ) ; they neither st and ardize clinical decisions nor lead to uniform implementation of clinical interventions , although these are their ultimate goals ( 65 , 67 , 68 ) . For example , it would be difficult to reduce variability with a protocol that required the clinician to determine whether the patient looked septic unless the state looked septic was explicitly defined by identifying the specific observations that lead to this clinical conclusion . When so defined , data that determine the presence of the state looked septic could be entered directly as inputs to a decision-support tool without the need for judgment by a clinician . Table 1 . Decision-Support Products and Attributes Computerized protocol s used for complex clinical problems can contain much more detail than textual guidelines or paper-based flow diagrams ( 67 ) . Increased detail allows point-of-care generation of patient-specific therapy instructions that can be carried out by different clinicians with almost no interclinician variability ( 69 ) . This can make both formal clinical inquiries ( for example , r and omized trials ) and informal clinical inquiries ( for example , some continuous quality improvement efforts or clinical practice evaluations ) more robust ( 52 , 69 ) . Explicit Computerized Protocol s Explicit rule-based computer systems are used in the most rigorous applications of algorithms in point-of-care clinical decision support ( 10 , 25 , 52 - 54 , 67 , 70 - 74 ) . Computerized protocol s have been shown to produce favorable changes in clinical ly important outcomes ( 10 , 25 , 27 , 54 , 57 - 59 , 70 , 72 , 75 - 77 ) . The immediacy of point-of-care decision support ( 67 ) differs from the more flexible time periods in which both decision trees ( 78 ) and computerized algorithms are implemented in consultative services ( 79 ) . Although st and ardization of clinical decisions has been declared unreasonable ( 66 ) , results from computerized protocol applications for mechanical ventilation suggest otherwise ( 53 , 54 , 73 ) . St and ardization of clinical decisions may have affected the conduct of certain r and omized , controlled clinical trials ( 53 , 54 ) in which success was previously thought to be unlikely ( 80 ) . The computerized protocol strategy I describe falls within , or between , the categories of reminders and consultants outlined by Miller and Goodman ( 60 ) . At LDS Hospital , computerized mechanical ventilation protocol s have been used to support more than 250 patients with ARDS ( Figure 1 ) for more than 100 000 hours ( 52 , 53 , 73 , 85 ) . Compliance of LDS Hospital physicians with protocol instructions was 95 % ( 54 , 86 ) . These computerized ARDS mechanical ventilation protocol s have been exported to st and -alone bedside personal computers in 10 other hospitals ( Figure 2 ) . These other hospitals have used the protocol s to st and ardize clinical decision making for 103 patients with ARDS in a recently completed clinical trial ( 54 , 87 ) ; physician compliance was 94 % . A total of 38 546 instructions were generated during 32 055 hours of application ( 36 % of instructions were for positive end-expiratory pressure , 40 % were for fraction of inspiratory oxygen , 6 % were for tidal volume , 12 % were for ventilatory rate , and 4 % were for minute ventilation ) ( 54 ) . Physicians objected to only 0.3 % of the 38 546 instructions . Survival was comparable in the two experimental groups , but barotrauma was significantly less likely in the group that received st and ardized decisions from the computerized protocol . The 94 % rate of physician compliance is much higher than the 30 % to 60 % rate seen in studies of computerized decision support protocol s for antibiotic and diabetes guidelines ( 25 , 27 ) . These results indicate that an explicit method of care BACKGROUND Paper-based nomograms are reasonably effective for achieving glycemic control but have low adherence and are less adaptive than nurses ' judgment . OBJECTIVE To compare efficacy ( glucose control ) and safety ( hypoglycemia ) achieved by use of a paper nomogram versus nurses ' judgment . METHODS Prospect i ve , r and omized , open-label , crossover trial in an intensive care unit in postoperative patients with glucose concentrations greater than 8 mmol/L. Consenting nurses with at least 1 year of experience were r and omized to use either their judgment or a vali date d paper-based nomogram for glucose control . After completion of 2 study shifts , the nurses used the alternative method for the next 2 study shifts . Glucose target level and safety and efficacy boundaries were the same for both methods . The primary end point was area under glucose time curve per hour . RESULTS Thirty-four nurses contributed 95 shifts of data ( 44 nomogram-directed , 51 nurse-directed ) . Adherence to the nomogram was higher in the nomogram group than hypothetical adherence in the nurse-directed group for correct adjustments in insulin infusion ( 70 % vs 37 % ; P < .001 ) and glucose checks ( 58 % vs 43 % ; P = .008 ) . The primary end point did not differ between the 2 groups ( mean , 9.0 mmol/L ; SD , 3.5 vs mean , 8.3 mmol/L ; SD , 2.1 ; P = .08 ) . Glucose variability , amount of time patients were hypoglycemic or hyperglycemic , and number of glucose checks performed were similar in the 2 groups . CONCLUSIONS In an intensive care unit where nurses generally accepted the need for tight glucose control , nurse-directed control was as effective and as safe as nomogram-based control |
12,198 | 24,833,288 | Use of prostagl and ins result ed in less need for manual removal of placenta , severe postpartum haemorrhage and blood transfusion but none of the differences reached statistical significance .
Much larger , adequately powered studies are needed to confirm that these clinical ly important beneficial effects are not just chance findings .Similarly , no differences were detected between prostagl and ins and placebo in mean blood loss or the mean time from injection to placental removal ( minutes ) or side-effects ( vomiting , headache , pain and nausea between injection and discharge from the labour ward ) except for ' shivering ' which was more frequent in women who received prostagl and in . | BACKGROUND Retained placenta affects 0.5 % to 3 % of women following delivery and it is a major cause of maternal death due to postpartum haemorrhage .
Usually , retained placenta has been managed by manual removal or curettage under anaesthesia , which may be associated with haemorrhage , infection and uterine perforation .
Medical management to facilitate the delivery of the retained placenta could be a safe alternative avoiding surgical intervention .
OBJECTIVES To assess the effectiveness and safety of prostagl and ins for the management of retained placenta . | OBJECTIVE To evaluate the efficacy and safety of misoprostol among patients with retained placenta in a low-re source setting . METHODS A prospect i ve , multicenter , r and omized , double-blind , placebo-controlled trial was carried out in Tanzania between April 2008 and November 2011 . It included patients who delivered at a gestational age of 28 weeks or more and had blood loss of 750 mL or less at 30 minutes after delivery . Sublingual misoprostol ( 800 μg ) was compared with placebo as the primary treatment . Power analysis showed that 117 patients would be required to observe a reduction of 40 % in the incidence of manual removal of the placenta ( MRP ; P=0.05 , 80 % power ) , the primary outcome . The secondary outcomes were blood loss and number of blood transfusions . RESULTS Interim analysis after recruitment of 95 patients showed that incidence of MRP , total blood loss , and incidence of blood transfusions were similar in the misoprostol ( MRP , 40 % ; blood loss , 803 mL ; blood transfusion , 15 % ) and placebo ( MRP , 33 % , blood loss 787 mL , blood transfusion , 23 % ) groups . The trial was stopped because continuation would not alter the interim conclusion that misoprostol was ineffective . CONCLUSION Treatment with misoprostol was found to have no clinical ly significant beneficial effect among women with retained placenta . CLINICAL TRIAL REGISTRATION Current Controlled Trials IS RCT N16104753 OBJECTIVE To assess the effect of injecting an uterotonic agent in the umbilical vein during the third stage of labor in women with retained placentas . METHODS In this prospect i ve clinical study , 75 women with retained placentas received 20 mL of a 0.9 % saline solution with either 20 IU of oxytocin ( n=54 ) , 0.5 mg of carboprost tromethamine ( n=7 ) , or 0.2 mg of methylergometrine ( n=14 ) injected in the umbilical vein after clamping . The treatment success was determined by the clinical signs of placental ablation . RESULTS There were no statistically significant differences among the 3 therapeutic groups regarding age , parity , risk factors , pregnancy duration , type of delivery ( spontaneous , induced , or augmented ) , or possible early postpartum complications caused by the intraumbilical injection . The rates of therapeutic success were 76.9 % in the oxytocin group , 85.7 % in the synthetic prostagl and in group , and 64.2 % in the methylergometrine group . CONCLUSION The intraumbilical injection of uterotonics is a noninvasive , effective , and clinical ly safe method of shortening the third stage of labor in women with retained placentas OBJECTIVE The purpose of this study was to determine the extent that the administration of sulprostone reduces the need for manual removal of the placenta in patients with retained placenta . STUDY DESIGN A double-blinded sequential r and omized controlled trial of sulprostone versus placebo was conducted among 103 patients with retained placenta . RESULTS In the first phase of this sequential study , sulprostone was compared with placebo . The null hypothesis of equal effectiveness of both treatments was rejected after 50 patients . In patients with retained placenta , the placenta was expelled after sulprostone in 13 of 24 cases ( 51.8 % , bias adjusted ) , whereas expulsion after placebo was achieved in only 4 of 26 cases ( 17.6 % , bias adjusted ) . The difference was significant ( P = .034 ) . In the second phase of the study , in which the placebo arm was stopped , results were confirmed ; in 25 of 53 patients ( 47 % ) , the placenta was expelled . CONCLUSION Sulprostone reduces the need for the manual removal of the placenta by 49 % Background . Manual removal of placenta is performed in 1–3 % of cases , and whilst a well established and relatively safe procedure , it is not without complications , which include infection , hemorrhage , uterine rupture , and occasional maternal death . Methods . A three‐arm r and omized controlled trial of 50 IU Syntocinon ( in 30 ml N saline ) versus 800 mcg misoprostol ( in 30 ml N saline ) versus 30 ml N saline alone ( control ) , injected into the placental bed via the umbilical vein using the Pipingas method . A group sequential research model ( triangular test : PEST4 ) was adopted to minimize the sample size , as retained placenta is a relatively uncommon condition . Results . No significant difference in the rate of manual removal was observed between the control and Syntocinon groups . On triggering the automatic stopping rule for this arm of the trial all subsequent cases recruited were allocated to receive either Syntocinon or misoprostol . After a total of 54 cases a significant reduction in manual removal of placenta was observed in the misoprostol group , triggering the automatic stopping rule and terminating the trial . Conclusion . Misoprostol ( 800 mcg ) dissolved in 30 ml N saline and administered by intraumbilical injection using the Pipingas technique significantly reduces the need for manual removal for retained adherent placenta , whereas Syntocinon has similar effectiveness to injection of N saline alone The length of the third stage of labour is a potential modifiable risk factor for postpartum haemorrhage at vaginal delivery , but there is no definitive evidence that early intervention to remove the placenta manually will prevent postpartum haemorrhage . We report a wide variation between countries in Europe in policies about the timing of manual removal of placenta . Two groups of countries with clearly divergent policies were identified . A r and omised controlled trial is needed to provide definitive evidence on the risks and benefits of manual removal of placenta at different timings after vaginal delivery INTRODUCTION This study aim ed to determine the incidence of , and identify independent risk factors to retained placenta in Ile-Ife , southwestern Nigeria . METHODS This was a prospect i ve case-control study involving 120 women with retained placenta after vaginal birth at the Obafemi Awolowo University Teaching Hospital , Ile-Ife , southwestern Nigeria over a period of seven years . Two consecutive normal deliveries after each retained placenta served as controls . Following a bivariate analysis , a multivariate logistic regression model was constructed in order to define independent risk factors for retained placenta while controlling for confounding variables . RESULTS During the study period , there were 120 cases of retained placenta , and the total number of deliveries was 6,160 , making the incidence 1.9 percent . Independent risk factors associated with retained placenta include non-use of antenatal care ( odds-ratio [ OR ] 22.71 , 95 percent confidence interval [ CI ] 10.5 - 49.12 , p-value is less than 0.000 ) , previous retained placenta ( OR 15.22 , 95 percent CI 3.30 - 70.19 , p-value is less than 0.000 ) , previous caesarean section ( OR 12.00 , 95 percent CI 2.05 - 70.19 , p-value is less than 0.006 ) , maternal age 35 years or more ( OR 7.10 , 95 percent CI 1.5 - 32.40 , p-values is less than 0.012 ) , gr and multiparity ( OR 6.63 , 95 percent CI 1.88 - 23.40 , p-value is less than 0.003 ) , previous dilatation and curettage ( OR 4.44 , 95 percent CI 1.69 - 11.63 , p-value is less than 0.002 ) , preterm delivery ( OR 3.12 , 95 percent CI 1.12 - 8.68 , p-value is less than 0.029 ) and placenta weight less than 501 g ( OR 2.91 , 95 percent CI 1.34 - 6.32 , p-value is less than 0.007 ) . CONCLUSION Women with identifiable risk factors should be targeted for the prevention of retained placenta . There is a need for the training of birth attendants in the proper conduct of delivery and third stage of labour to prevent placenta retention and postpartum haemorrhage OBJECTIVE : To identify risk factors for immediate postpartum hemorrhage after vaginal delivery in a South American population . METHODS : This was a prospect i ve cohort study including all vaginal births ( N=11,323 ) between October and December 2003 and October and December 2005 from 24 maternity units in two South American countries ( Argentina and Uruguay ) . Blood loss was measured in all births using a calibrated receptacle . Moderate postpartum hemorrhage and severe postpartum hemorrhage were defined as blood loss of at least 500 mL and at least 1,000 mL , respectively . RESULTS : Moderate and severe postpartum hemorrhage occurred in 10.8 % and 1.9 % of deliveries , respectively . The risk factors more strongly associated and the incidence of moderate postpartum hemorrhage in women with each of these factors were : retained placenta ( 33.3 % ) ( adjusted odds ratio [ OR ] 6.02 , 95 % confidence interval [ CI ] 3.50–10.36 ) , multiple pregnancy ( 20.9 % ) ( adjusted OR 4.67 , CI 2.41–9.05 ) , macrosomia ( 18.6 % ) ( adjusted OR 2.36 , CI 1.93–2.88 ) , episiotomy ( 16.2 % ) ( adjusted OR 1.70 , CI 1.15–2.50 ) , and need for perineal suture ( 15.0 % ) ( adjusted OR 1.66 , CI 1.11–2.49 ) . Active management of the third stage of labor , multiparity , and low birth weight were found to be protective factors . Severe postpartum hemorrhage was associated with retained placenta ( 17.1 % ) ( adjusted OR 16.04 , CI 7.15–35.99 ) , multiple pregnancy ( 4.7 % ) ( adjusted OR 4.34 , CI 1.46–12.87 ) , macrosomia ( 4.9 % ) ( adjusted OR 3.48 , CI 2.27–5.36 ) , induced labor ( 3.5 % ) ( adjusted OR 2.00 , CI 1.30–3.09 ) , and need for perineal suture ( 2.5 % ) ( adjusted OR 2.50 , CI 1.87–3.36 ) . CONCLUSION : Many of the risk factors for immediate postpartum hemorrhage in this South American population are related to complications of the second and third stage of labor . LEVEL OF EVIDENCE : OBJECTIVE To determine the frequency , causes and outcome of patients with retained placenta . METHODS Descriptive case series . This study was carried out at Liaquat University Hospital , Gynae Unit-I , from January 2005 to December 2007 . Two years retrospective and one year prospect i ve analysis of patients was done according to age , parity , causes , place of delivery , person who conducted the delivery , conservative and surgical procedures , maternal morbidity and mortality . Patients were examined and appropriate investigations were done . The patients who came with or developed retained placenta at Liaquat University Hospital were included in the study . The patients having retained placenta due to uterine abnormalities were excluded from the study . All the information was collected on a pre design ed proforma and analyzed on SPSS version 10.0 . RESULTS About 8782 patients were admitted during the specified period . Ninety patients had retained placenta . Frequency of retained placenta was 37.7 % in women of age group 26 to 30 years , 26.6 % upto age of 35 years , 22.2 % in age 20 - 25 years , it was low between 36 - 40 years of age , while the frequency was high in women of low parity ( 44.4 % ) . Causes included augmentation by oxytocics in 38.8 % , manipulation 38.8 % , inertia 14.4 % and tumour ( fibroid ) 7.7 % . Majority of patients ( 60 % ) had a home delivery . Delivery by Dai was done in 72.2 % . The commonest complication was anaemia 48.8 % , followed by puerperal pyrexia 24.4 % , hypovolaemic shock 22.2 % , acute renal failure 3.3 % and hepatic failure in 1.1 % respectively . CONCLUSION Retained placenta is a frequent cause of maternal morbidity in Pakistan Background Retained placenta is one of the common causes of maternal mortality in developing countries where access to appropriate obstetrical care is limited . Current treatment of retained placenta is manual removal of the placenta under anaesthesia , which can only take place in larger health care facilities . Medical treatment of retained placenta with prostagl and ins E1 ( misoprostol ) could be cost-effective and easy-to-use and could be a life-saving option in many low-re source setting s. The aim of this study is to assess the efficacy and safety of sublingually administered misoprostol in women with retained placenta in a low re source setting . Methods Design : Multicentered r and omised , double-blind , placebo-controlled trial , to be conducted in 5 hospitals in Tanzania , Africa . Inclusion criteria : Women with retained placenta , at a gestational age of 28 weeks or more and blood loss less than 750 ml , 30 minutes after delivery of the newborn despite active management of third stage of labour . Trial Entry & R and omisation & Study Medication : After obtaining informed consent , eligible women will be allocated r and omly to the treatment groups using numbered envelopes that will be r and omized in variable blocks containing identical capsules with either 800 microgram of misoprostol or placebo . The drugs will be given sublingually . The women , maternal care providers and research ers will be blinded to treatment allocation . Sample Size : 117 women , to show a 40 % reduction in manual removals of the placenta ( p = 0.05 , 80 % power ) . The r and omization will be misoprostol : placebo = 2:1 Primary Study Outcome : Expulsion of the placenta without manual removal . Secondary outcome is the number of blood transfusions . Discussion This is a protocol for a r and omized trial in a low re source setting to assess if medical treatment of women with retained placenta with misoprostol reduces the incidence of manual removal of the placenta . Clinical Trial Registration Current Controlled Trials IS RCT |
12,199 | 23,470,572 | At 1 and 5 years , dysphagia and gas-related symptoms are lower after 180-degree LAF than after LNF , and esophageal acid exposure and esophagitis are similar , with no differences in heartburn scores , patient satisfaction , dilatations , and reoperation rate . | OBJECTIVE To compare short- and long-term outcome after 180-degree laparoscopic anterior fundoplication ( 180-degree LAF ) with laparoscopic Nissen fundoplication ( LNF ) .
SUMMARY OF BACKGROUND DATA LNF is currently the most frequently performed surgical therapy for gastroesophageal reflux disease .
Alternatively , 180-degree LAF has been alleged to reduce troublesome dysphagia and gas-related symptoms , with similar reflux control . | HYPOTHESIS Laparoscopic anterior 90 degrees partial fundoplication for gastroesophageal reflux is associated with a lower incidence of postoperative dysphagia and other adverse effects compared with laparoscopic Nissen fundoplication . DESIGN A multicenter , prospect i ve , double-blind , r and omized controlled trial . SETTING Nine university teaching hospitals in 6 major cities in Australia and New Zeal and . PARTICIPANTS One hundred twelve patients with proven gastroesophageal reflux disease presenting for laparoscopic fundoplication were r and omized to undergo either a Nissen ( 52 patients ) or an anterior 90 degrees partial procedure ( 60 patients ) . Patients with esophageal motility disorders , patients requiring a concurrent abdominal procedure , and patients who had undergone previous antireflux surgery were excluded from this study . INTERVENTIONS Laparoscopic Nissen fundoplication with division of the short gastric vessels or laparoscopic anterior 90 degrees partial fundoplication . MAIN OUTCOME MEASURES Independent assessment of dysphagia , heartburn , and overall satisfaction 1 , 3 , and 6 months after surgery using multiple clinical grading systems . Objective measurement of esophageal manometric parameters , esophageal acid exposure , and endoscopic assessment . RESULTS Postoperative dysphagia , and wind-related adverse effects were less common after a laparoscopic anterior 90 degrees partial fundoplication . Relief of heartburn was better following laparoscopic Nissen fundoplication . Overall satisfaction was better after anterior 90 degrees partial fundoplication . Lower esophageal sphincter pressure , acid exposure , and endoscopy findings were similar for both procedures . CONCLUSIONS At the 6-month follow-up , laparoscopic anterior 90 degrees culine partial fundoplication is followed by fewer adverse effects than laparoscopic Nissen fundoplication with full fundal mobilization , and it achieves a higher rate of satisfaction with the overall outcome . However , this is offset to some extent by a greater likelihood of recurrent gastroesophageal reflux symptoms BACKGROUND Total fundoplication for gastro-oesophageal reflux disease may be followed by unwanted side-effects . A r and omized trial demonstrated that an anterior 180 degrees partial fundoplication achieved effective reflux control and was associated with fewer side-effects in the short term than total fundoplication . This paper reports longer-term ( 5 year ) outcomes from that trial . METHODS Between December 1995 and June 1997 , 107 patients were r and omized to undergo either laparoscopic total fundoplication or a laparoscopic anterior 180 degrees fundoplication . After 5 years , 101 of 103 eligible patients ( 51 total , 50 anterior ) were available for follow-up . Each patient was interviewed by a single blinded investigator and a st and ardized question naire was completed . The question naire focused on symptoms and overall satisfaction with the results of fundoplication . RESULTS There were no significant differences between the two groups with regard to control of heartburn or patient satisfaction with the overall outcome . Dysphagia , measured by a visual analogue score for solid food and a composite dysphagia score , was worse at 5 years after total fundoplication . Symptoms of bloating , inability to belch and flatulence were also more common after total fundoplication . Reoperation was required for dysphagia in three patients after total fundoplication and for recurrent reflux in three patients after anterior fundoplication . CONCLUSION Anterior 180 degrees partial fundoplication was as effective as total fundoplication for managing the symptoms of gastro-oesophageal reflux in the longer term . It was associated with a lower incidence of side-effects , although this was offset by a slightly higher risk of recurrent reflux symptoms Objective : To compare 10 years outcome of a multicenter r and omized controlled trial on laparoscopic ( LNF ) and conventional Nissen fundoplication ( CNF ) , with focus on effectiveness and reoperation rate . Summary of Background Data : LNF has replaced CNF as surgical treatment for gastroesophageal reflux disease ( GERD ) . Decisions are based on equal short-term effectiveness and reduced morbidity , but confirmation by long-term level 1 evidence is lacking . Methods : From 1997 to 1999 , 177 proton pump inhibitor (PPI)-refractory GERD patients were r and omized to undergo LNF or CNF . The 10 years results of surgery on reflux symptoms , general health , PPI use , and reoperation rates , are described . High-resolution manometry , 24-hour pH-impedance monitoring and barium swallow were performed in symptomatic patients only . Results : A total of 148 patients ( 79 LNF , 69 CNF ) participated in this 10-year follow-up study . GERD symptoms were relieved in 92.4 % and 90.7 % ( NS ) after LNF and CNF , respectively . Severity of heartburn and dysphagia were similar , but slightly more patients had relief of regurgitation after LNF ( 98.7 % vs. 91.0 % ; P = 0.030 ) . The percentage of patients using PPIs slowly increased with time in both groups to 26.6 % for LNF and 22.4 % for CNF ( NS ) . General health ( 74.7 % vs. 72.7 % ; NS ) and quality of life ( visual analogue scale score : 65.3 vs. 61.4 ; NS ) improved similarly in both groups . The percentage of patients who would have opted for surgery again was similar as well ( 78.5 % vs. 72.7 % ; NS ) . Twice as many patients underwent reoperation after CNF compared with LNF ( 12 [ 15.2 % ] vs. 24 [ 34.8 % ] ; P = 0.006 ) , including a higher number of incisional hernia corrections ( 2 vs. 9 ; P = 0.015 ) . Mean interval between operation and reintervention was longer after CNF ( 22.9 vs. 50.6 months ; P = 0.047 ) . Of the patients who were dependent on daily PPI therapy at 10 years ( LNF 10 , CNF 10 ) , 7 patients ( LNF 3 , CNF 4 ) had recurrent GERD on pH-impedance monitoring , 5 of them with some form of anatomic recurrence . A total of 13 of 20 ( 65.0 % ) patients did not have recurrent GERD . Fourteen patients had an abnormal high-resolution manometry . Conclusions : CNF carries a higher risk for surgical reintervention compared with LNF , mainly due to incisional hernia corrections . The 10-year effectiveness of LNF and CNF is comparable in terms of improvement of GERD symptoms , PPI use , quality of life , and objective reflux control . Consequently , the long-term results from this trial lend level 1 support to the use of LNF as the surgical procedure of choice for GERD BACKGROUND The effect of total ( Nissen ) and anterior partial fundoplication ( APF ) for the surgical treatment of gastroesophageal reflux disease ( GERD ) on the motor behavior of the esophagogastric axis has not been fully assessed . The purpose of this study was to assess any alterations in lower esophageal sphincter ( LES ) and gastric fundus motor parameters in GERD patients after Nissen or APF fundoplication . METHODS Twenty four patients with documented GERD underwent either laparoscopic Nissen fundoplication ( n = 12 ) or laparoscopic APF ( n = 12 ) . Preoperative and postoperative stationary esophageal manometry included assessment of LES resting and postdeglutition relaxation pressures , intragastric pressure , and LES transient relaxations in the left lateral and upright positions and after gastric distension . RESULTS Both types of fundoplication result ed in significant increases in LES resting ( P < 0.001 ) and postdeglutition relaxation pressure ( P < 0.001 ) in both positions and after gastric distention . Intragastric pressure increased only after Nissen fundoplication in the postgastric distention state ( P = 0.01 ) . Transient LES relaxations were equally abolished after both procedures . All postoperative changes were to a similar level after either procedure with the exception of intragastric pressure after gastric distention , which was significantly higher after total than after partial fundoplication ( P = 0.04 ) . CONCLUSIONS Both procedures equally increase LES resting and postdeglutition relaxation pressures and abolish transient LES relaxations at all states . The significantly higher intragastric pressure at the postgastric distention state after Nissen fundoplication could possibly explain the higher incidence of epigastric fullness and discomfort after this type of antireflux surgery In the operative management of gastro‐oesophageal reflux , a balance must be achieved between adequate control of reflux and excessive dysphagia . The ideal technique is not known . A r and omized study was performed to determine whether laparoscopic anterior fundoplication is associated with a lower incidence of postoperative dysphagia than laparoscopic Nissen fundoplication , while achieving equivalent control of reflux BACKGROUND AND AIMS The purpose of this study was to determine whether esophageal dysmotility affects symptoms of gastroesophageal reflux disease or clinical outcome after laparoscopic fundoplication and whether esophagus motor function changes postoperatively . METHODS Two hundred patients with a history of long-st and ing gastroesophageal reflux disease were investigated by clinical assessment , upper gastrointestinal endoscopy , esophageal manometry , and 24-hour pH monitoring between May 1999 and May 2000 . Patients were stratified according to presence or absence of esophageal dysmotility ( each n = 100 ) and r and omized to either 360 degrees ( Nissen ) or 270 degrees ( Toupet ) fundoplication . At a 4-month postoperative follow-up , preoperative tests were repeated . RESULTS Preoperative esophageal dysmotility was associated with more severe reflux symptoms , more frequent resistance to medical treatment ( 64 % vs. 49 % ; P < 0.05 ) , and greater decrease in lower esophageal sphincter pressure ( 9.5 + /- 5.3 vs. 12.4 + /- 6.7 mm Hg ; P < 0.0005 ) compared with normal motility . Postoperatively , clinical outcome and reflux recurrence ( 21 % vs. 14 % ) were similar . Esophageal motility remained unchanged in 85 % of patients and changed from pathologic to normal in 20 ( 10 Nissen/10 Toupet ) and vice versa in 9 ( 8 Nissen/1 Toupet ) patients . CONCLUSIONS Esophageal dysmotility ( 1 ) reflects more severe disease ; ( 2 ) does not affect postoperative clinical outcome ; ( 3 ) is not corrected by fundoplication , independent of the surgical procedure performed ; ( 4 ) may occur as a result of fundoplication ; and ( 5 ) requires no tailoring of surgical management Objective The aim of the study was to compare the efficacy and mechanical consequences of 2 partial fundoplications performed laparoscopically under the framework of a r and omized , controlled clinical trial . Summary Background Data Although laparoscopic total fundoplication procedures have proven their effectiveness in the control of gastroesophageal reflux , problems remain with the functional consequences after a supra-competent gastric cardia high-pressure zone . Partial fundoplications have been found to be associated with fewer mechanical side effects . Patients and Methods During a 2-year period , 95 patients with gastroesophageal reflux disease were enrolled into a r and omized , controlled single-institution clinical trial comparing a partial posterior ( Toupét , n = 48 ) fundoplication and an anterior partial wrap ( Watson , n = 47 ) . All patients were assessed postoperatively at predefined time points , and the 12-month follow-up data are presented in terms of clinical results and 24-hour pH monitoring variables . Results Both patient groups were strictly comparable at the time of r and omization . All operations were completed laparoscopically , and no serious complications were encountered . During the first postoperative year , a difference regarding the control of reflux symptoms was observed in favor of the posterior fundoplication . Esophageal acid exposure ( % time pH < 4 ) was substantially reduced by both operations but to a significantly lower level after a Toupét compared with the Watson partial fundoplication ( 1.0 ± 0.3 vs. 5.6 ± 1.1 mean ± SEM ; p < 0.001 ) . Postfundoplication symptoms were infrequently recorded with no difference between the groups . Conclusions When performing a laparoscopic partial fundoplication , the posterior modification ( Toupét ) offers advantages in terms of better reflux control compared with an anterior type ( Watson ) This double‐blind , r and omized study compared outcomes of laparoscopic Nissen total fundoplication and anterior partial fundoplication carried out by a single surgeon in a private practice Objective : To compare longer term ( 5-year ) outcomes for reflux control and postsurgery side effects after laparoscopic anterior ( 90 ° and 180 ° ) partial versus Nissen fundoplication for gastroesophageal reflux . Background : Laparoscopic Nissen fundoplication is the most frequently performed surgical procedure for gastroesophageal reflux . It achieves excellent control of reflux , but in some patients it is followed by troublesome side effects . To reduce the risk of side effects laparoscopic anterior partial fundoplication variants have been advocated , although some studies suggest poorer reflux control . Methods : From 1995 to 2003 , 461 patients with gastroesophageal reflux were enrolled in 4 r and omized controlled trials comparing anterior partial versus Nissen fundoplication . Two trials evaluated anterior 180 ° and 2 anterior 90 ° partial fundoplication . The original trial data were combined , and a re analysis from original data was undertaken to determine outcomes at 5 years follow-up . Reflux symptom control and side effects were evaluated in a blinded fashion using st and ardized question naires , including 0 to 10 analog scores ( 0 = no symptoms , 10 = severe symptoms ) . Results : At 5 years , patients who underwent an anterior 90 ° or 180 ° partial fundoplication had less side effects than those who underwent Nissen fundoplication and were equally satisfied with the overall outcome . Reflux control , measured by heartburn scores and antisecretory medication use , was similar for anterior 180 ° partial versus Nissen fundoplication , but inferior after anterior 90 ° partial versus Nissen fundoplication . Conclusions : Anterior 180 ° partial fundoplication achieves durable control of reflux symptoms and fewer side effects compared with Nissen fundoplication . Reflux control after anterior 90 ° partial fundoplication appears less effective than after Nissen fundoplication . This data supports the use of anterior 180 ° partial fundoplication for the surgical treatment of gastroesophageal reflux Objective : The purpose of this prospect i ve study was to compare the subjective and objective outcome of laparoscopic ( LNF ) and conventional Nissen fundoplication ( CNF ) up to 5 years after surgery as obtained in a multicenter r and omized controlled trial . Summary of Background Data : LNF is regarded as surgical treatment of first choice for refractory gastroesophageal reflux disease by many surgeons based on several short- and mid-term studies . The long-term efficacy of Nissen fundoplication , however , is still question ed as objective data gathered from prospect i ve studies are lacking . Methods : From 1997 to 1999 , 177 patients were r and omized to undergo LNF or CNF . Five years after surgery , all patients were requested to fill in question naires and to undergo esophageal manometry and 24-hour pH-metry . Results : A total of 148 patients agreed to participate in the follow-up study : 79 patients after LNF and 69 after CNF . Of these , 97 patients ( 48 LNF , 49 CNF ) consented to undergo esophageal manometry and 24-hour pH-metry . At 5 years follow-up , 20 patients had undergone reoperation : 12 after LNF ( 15 % ) and 8 after CNF ( 12 % ) . There was no difference in subjective outcome , with overall satisfaction rates of 88 % and 90 % , respectively . Total esophageal acid exposure times ( pH < 4 ) were 2.1 % ± 0.5 % and 2.0 % ± 0.6 % , respectively ( P = 0.21 ) . Antisecretory medication was taken daily in 14 % and 16 % , respectively ( P = 0.29 ) . There was no correlation between medication use and acid exposure and indices of symptom-reflux association ( symptom index and symptom association probability ) . No significant differences between subjective and objective results at 3 to 6 months and results obtained at 5 years after surgery were found . Conclusions : The effects of LNF and CNF on general state of health and objective reflux control are sustained up to 5 years after surgery and the long-term results of LNF and CNF are comparable . A substantial minority of patients in both groups had a second antireflux operation or took antisecretory drugs , although the use of those medications did not appear to be related to abnormal esophageal acid exposure BACKGROUND It has been proposed that partial fundoplication is associated with less incidence of postoperative dysphagia and consequently is more suitable for patients with gastroesophageal reflux disease ( GERD ) and impaired esophageal body motility . The aim of this study was to assess whether outcomes of Toupet fundoplication ( TF ) are better than those of Nissen-Rossetti fundoplication ( NF ) in patients with GERD and low-amplitude esophageal peristalsis . STUDY DESIGN Thirty-three consecutive patients with proved GERD and amplitude of peristalsis at 5 cm proximal to lower esophageal sphincter ( LES ) less than 30 mmHg were r and omly allocated to undergo either TF ( 19 patients : 11 men , 8 women ; mean age : 61.7 + /- 8.7 SD years ) or NF ( 14 patients : 7 men , 7 women ; mean age : 59.2 + /- 11.5 years ) , both by the laparoscopic approach . Pre- and postoperative assessment included clinical question naires , esophageal radiology , esophageal transit time study , endoscopy , stationary manometry , and 24-hour ambulatory esophageal pH testing . RESULTS Duration of operation was significantly prolonged in the TF arm ( TF : 90 + /- 12 minutes versus NF : 67 + /- 15 minutes ; p < 0.001 ) . At 3 months postoperatively , the incidences of dysphagia ( grade s I , II , III ) and gas-bloat syndrome were higher after NF than after TF ( NF : 57 % versus TF : 16 % ; p < 0.01 and NF : 50 % versus TF : 21 % ; p = 0.02 , respectively ) , but decreased to the same level in both groups at the 1-year followup ( NF : 14 % versus TF : 16 % and NF : 21 % versus TF : 16 % , respectively ) . At 3 months postoperatively , patients with NF presented with significantly increased LES pressure than those with TF ( p = 0.02 ) , although LES pressure significantly increased after surgery in both groups , as compared with preoperative values . Amplitude of esophageal peristalsis at 5 cm proximal to LES increased postoperatively to the same extent in both groups ( TF , preoperatively : 21 + /- 6 mmHg versus postoperatively : 39 + /- 12 mmHg ; p < 0.001 , and NF , preoperatively : 20 + /- 8 mmHg versus postoperatively : 38 + /- 12 mmHg ; p < 0.001 ) . Reflux was abolished in all patients of both groups . CONCLUSIONS Both TF and NF efficiently control reflux in patients with GERD and low amplitude of esophageal peristalsis . Early in the postoperative period , TF is associated with fewer functional symptoms , although at 1 year after surgery those symptoms are reported at similar frequencies after either procedure Introduction : Fundoplication techniques for treatment of gastroesophageal reflux are discussed concerning impairments and success . This r and omized trial was conducted to compare Nissen ’s wrap and the anterior partial technique ( Dor ) concerning patients ’ quality of life ( QoL ) and functional data after a mid-term follow-up . Methods : In a 24-month period , 64 patients were equally r and omized into group A ( Nissen ’s fundoplication ) and group B ( 180 ° anterior partial fundoplication ) . After a mean follow-up of 18 months , all patients were examined and interviewed using st and ardized QoL question naires ( Gastrointestinal Quality of Life Index ) , Visick score , 24-hour pH-metry and esophageal manometry . Data of 57 patients ( group A : 27 , group B : 30 ) could be analyzed . Results : After partial fundoplication , 9 patients ( 30 % ) stated the operative results were worse than perfect . Only 2 patients ( 7 % ) evaluated the outcome after Nissen ’s fundoplication as unsuccessful ( p = 0.04 ) . However , postoperative Gastrointestinal Quality of Life Index showed no differences between groups ( p = 0.5 ) . Additionally , functional data were not different ( DeMeester 10 vs. 12 , p = 0.17 , and lower esophageal sphincter pressure 13 vs. 12 mm Hg , p = 0.5 ) . Conclusion : The anterior partial fundoplication technique did not lead to disadvantages in postoperative QoL , physiological function and reflux control when compared to Nissen ’s approach in a mid-term follow-up OBJECTIVE To determine whether division of the short gastric vessels ( SGVs ) and full mobilization of the gastric fundus is necessary to reduce the incidence of postoperative dysphagia and other adverse sequelae of laparoscopic Nissen fundoplication . SUMMARY BACKGROUND DATA Based on historical and uncontrolled studies , division of the SGVs has been advocated during laparoscopic Nissen fundoplication to improve postoperative clinical outcomes . However , this modification has not been evaluated in a large prospect i ve r and omized trial . METHODS One hundred two patients with proven gastroesophageal reflux disease presenting for laparoscopic Nissen fundoplication were prospect ively r and omized to undergo fundoplication with ( 52 patients ) or without ( 50 patients ) division of the SGVs . Patients with esophageal motility disorders , patients requiring a concurrent abdominal procedure , and patients who had undergone previous antireflux surgery were excluded . Patients were blinded to the postoperative status of their SGVs . Clinical assessment was performed by a blinded independent investigator who used multiple st and ardized clinical grading systems to assess dysphagia , heartburn , and patient satisfaction 1 , 3 , and 6 months after surgery . Objective measurement of lower esophageal sphincter pressure , esophageal emptying time , and distal esophageal acid exposure and radiologic assessment of postoperative anatomy were also performed . RESULTS Operating time was increased by 40 minutes ( median 65 vs. 105 ) by vessel division . Perioperative outcomes and complications , postoperative dysphagia , relief of heartburn , and overall satisfaction were not improved by dividing the SGVs . Lower esophageal sphincter pressure , acid exposure , and esophageal emptying times were similar for the two groups . CONCLUSION Division of the SGVs during laparoscopic Nissen fundoplication did not improve any clinical or objective postoperative outcome To define the clinical role of antireflux surgical procedures a proper underst and ing of their mode of action is required . The aim of this study was to investigate the impact of total or posterior partial fundoplication on the function of the lower oesophageal sphincter ( LOS ) in the basal state as well as during stimulation Objectives : To compare in a prospect i ve , r and omized trial the long-term results of laparoscopic Heller myotomy plus Dor fundoplication versus laparoscopic Heller myotomy plus floppy-Nissen for achalasia . Summary Background Data : Anterior fundoplication is usually performed after Heller myotomy to control GER ; however , the incidence of postoperative GER ranges between 10 % and 30 % . Total fundoplication may aid in reducing GER rates . Methods : From December 1993 to September 2002 , 153 patients with achalasia underwent Heller laparoscopic myotomy plus antireflux fundoplication . Of these , 9 were excluded from the study . The remaining 144 patients were r and omly assigned to 2 treatment groups : Heller laparoscopic myotomy plus anterior fundoplication ( Dor procedure ) or Heller laparoscopic myotomy plus total fundoplication ( floppy-Nissen procedure ) . The primary end point was incidence of clinical and instrumental GER after a minimum of 60 months follow-up . The secondary end point was recurrence of dysphagia . Follow-up clinical assessment s were performed at 1 , 3 , 12 , and 60 months using a modified DeMeester Symptom Scoring System ( MDSS ) . Esophageal manometry and 24-hour pH monitoring were performed at 3 , 12 , and 60 months postoperative . Results : Of the 144 patients originally included in the study , 138 were available for long-term analysis : 71 ( 51 % ) underwent antireflux fundoplication plus a Dor procedure ( H + D group ) and 67 ( 49 % ) antireflux fundoplication plus a Nissen procedure ( H + N group ) . No mortality was observed . The mean follow-up period was 125 months . No statistically significant differences in clinical ( 5.6 % vs. 0 % ) or instrumental GER ( 2.8 % vs. 0 % ) were found between the 2 groups ; however , a statistically significant difference in dysphagia rates was noted ( 2.8 % vs. 15 % ; P < 0.001 ) . Conclusions : Although both techniques achieved long-term GER control , the recurrence rate of dysphagia was significantly higher among the patients who underwent Nissen fundoplication . This evidence supports the use of Dor fundoplication as the preferred method to re-establish GER control in patients undergoing laparoscopic Heller myotomy A r and omized trial of laparoscopic Nissen fundoplication and anterior 180 ° partial fundoplication was undertaken to determine whether the anterior procedure might reduce the incidence of dysphagia and other adverse outcomes following surgery for gastro‐oesophageal reflux disease . This study evaluated clinical outcomes after 10 years Objective : The aim of this study was to compare the long-term objective and subjective outcomes of laparoscopic and open Nissen fundoplication in a r and omized clinical trial with an 11-year follow-up . Summary Background Data : Laparoscopic Nissen fundoplication has become the method of choice in antireflux surgery , replacing its open counterpart despite the lack of long-term results from controlled clinical studies . Methods : Between April 1992 and June 1995 , 110 consecutive patients were r and omized to either laparoscopic ( LAP ) or conventional ( open ) Nissen fundoplication . The objective long-term follow-up consisted of an upper gastrointestinal endoscopy and a clinical assessment ; the subjective long-term outcome was investigated by personal interviews using a structured question naire . Results : Forty-nine patients in the LAP group and 37 patients in the open group were available for evaluation . Late subjective results , including postoperative symptoms and evaluation of the surgical result , were similar in both groups . With the benefit of hindsight , 73.7 % of the patients in the open group and 81.8 % in the LAP group would again choose surgical treatment ( P = 0.3042 ) . In the LAP group , there were 5 ( 13.2 % ) partially or totally disrupted plications compared with the 14 ( 40.0 % ) disrupted plications in the open group ( P = 0.0152 ) . There were 10 incisional hernias in the open group compared with none in the LAP group ( P < 0.001 ) . Conclusions : At long-term follow-up , the open and LAP approaches for the Nissen fundoplication have similar long-term subjective symptomatic outcome despite the significantly higher incidence of incisional hernias and defective fundic wraps at endoscopy in the open group defining laparoscopic Nissen fundoplication as the procedure of choice in surgical management of gastroesophageal reflux disease Although Nissen fundoplication is a very effective treatment for gastroesophageal reflux , it is associated with a small incidence of troublesome postoperative side effects . To prevent this , progressive modification of surgical techniques has led to the development of an anterior 90 degrees fundoplication . We undertook a prospect i ve r and omized trial to compare this procedure with Nissen fundoplication to determine whether it would achieve a better clinical outcome . Patients presenting to a single center for primary laparoscopic antireflux surgery were r and omized to undergo either an anterior 90 degrees fundoplication ( n = 40 ) or a Nissen fundoplication without division of the short gastric vessels ( n = 39 ) . Clinical question naires were used to assess outcome at 1 month , 3 - 6 months , and 12 months . Both patients and the clinical interviewer were masked as to which procedure was performed . Follow-up with endoscopy , esophageal manometry , and pH monitoring was also undertaken . Operating time was similar for the two procedures ( 60 minutes for anterior vs. 55 minutes for Nissen fundoplication ) . Early postoperative complications were more common after Nissen fundoplication ( 18 % vs. 5 % ) . Two patients underwent laparoscopic reoperation for recurrent reflux after anterior 90 degrees fundoplication , and four underwent laparoscopic reoperation after Nissen fundoplication ( dysphagia , 3 patients ; acute hiatus hernia , 1 patient ) . One year after surgery , dysphagia and other wind-related side effects were less common after anterior 90 degrees fundoplication . Control of reflux symptoms and satisfaction with the overall outcome was similar for the two procedures . Anterior 90 degrees fundoplication is followed by fewer side effects than Nissen fundoplication . This advantage is offset by a greater likelihood of reflux recurrence . However , this does not diminish patient satisfaction 5Although electronic search ing and publishing have made it easier to identify and obtain a report of a single r and omised trial , this can not be deemed a short-cut to obtaining an overall , balanced view of the effectiveness of the interventions investigated in the trial . Instead , similar trials need to be brought together . This bringing together needs to be done in as unbiased a way as possible . Traditional narrative review s , usually written by a recognised expert , are generally not systematic . Authors might simply not have the time to identify and bring together all relevant studies or they might actually seek to discuss and selectively combine trials that confirm their opinions and prejudices . A systematic review aims to circumvent this weakness by the use of a predefined , explicit methodology . The methods used include steps to minimise bias in the identification of relevant studies , in the selection criteria for inclusion , and in the collection of data . Guidance is available on the conduct , Background : The aim of the study was to compare the effect of laparoscopic anterior and posterior fundoplication on gastro‐oesophageal reflux disease by means of a prospect i ve r and omized controlled trial |
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