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12,800 | 25,221,617 | Our evidence suggested there might be no advantage of DPC over PC in reducing SSI in complicated appendicitis . | null | null |
12,801 | 12,242,114 | Radiation dose intensification and radiation sensitizer approaches have not demonstrated superior survival rates compared with conventionally fractionated doses of 50 - 60 Gy .
Post-operative external beam radiotherapy is recommended as st and ard therapy for patients with malignant glioma .
For patients older than age 70 , preliminary data suggest that the same survival benefit can be achieved with less morbidity using a shorter course of radiotherapy . | PURPOSE A systematic review was conducted to develop guidelines for radiotherapy in adult patients with newly diagnosed malignant glioma . | Efforts to improve local control and survival by increasing the dose of once‐daily radiation therapy beyond 70 Gray ( Gy ) for patients with malignant gliomas have as yet been unsuccessful . Hyperfractionated radiation therapy ( HF ) should allow for delivery of a higher total dose without increasing normal tissue late effects , whereas accelerated hyperfractionated radiation therapy ( AHF ) may minimize tumor re population by shortening overall treatment time . The Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized Phase I/II study of escalating doses of HF and AHF with carmustine ( bis‐chloroethyl nitrosourea [ BCNU ] ) for adults with supratentorial glioblastoma multiforme ( GBM ) or anaplastic astrocytoma ( AA ) . Primary study endpoints were overall survival and acute and chronic treatment‐related toxicity Thirty-two patients prospect ively identified as having poor prognosis high grade glioma , with a MRC prognostic score > 25 , were treated with a short palliative course of radiotherapy . A total dose of 36 Gy in 12 fractions was given to the tumour , including oedema and a 2 cm margin , using parallel pair fields prescribed to the midplane with MV photons . Twenty-eight patients completed treatment as planned , while four failed to complete treatment because of clinical deterioration or death . The median survival for the whole group was 16 weeks , with seven patients surviving for more than 6 months . Approximately two-thirds of the surviving patients remained at home after the completion of treatment . A matched case-control comparison with data from patients in previous MRC studies who had received a 6-week course of treatment shows that , for this group of patients , survival is similar ( hazard ratio 1.0 ; 95 % confidence interval ( CI ) 0.57 - 1.74 ) . The 95 % CI for the difference in median survival time excludes a reduction of more than 7 weeks with the 36 Gy course . This shortened radiotherapy regimen may therefore be satisfactory for most poor prognosis patients . However , patients with performance status 3 gained little benefit from treatment , and it is suggested that this group should have a trial period of assessment at home prior to a decision on treatment We used " high-dose " metronidazole , an " in vitro " and " in vivo " specific radiosensitizer of hypoxic cells , in a controlled trial to evaluate possible enhancement of radiation effect in patients with supratentorial glioblastomas . Thirty-six patients were stratified according to functional level and r and omly allocated within two weeks of operation to one of two therapeutic groups : Group 1 , radiation alone ; and Group 2 , radiation as in Group 1 but with high-dose metronidazole . We examined survival with the Kaplan-Meier probability plot and non-parametric tests . Patients in Group 2 had a 4 1/2-month delay between relapse and subsequent death ( P = 0.02 ) . This shift of the survival curves suggests a delay in the time of tumor regrowth consistent with the ability of metronidazole to make the hypoxic tumor cells less radioresistant . Nitroimidazole derivatives may be useful radiosensitizers in human solid tumors A r and omised pilot study is reported of d(15)+Be neutrons compared with 4 MV photons in the treatment of patients with astrocytoma . Sixteen patients were treated by photons and 18 by neutrons . Both treatments were well tolerated by patients . The median survival after photons was 11 months and after neutrons , 7 months . It was demonstrated that four of nine patients treated by neutrons had evidence at autopsy of radiation-induced brain damage . All had residual cancer . No patient treated by photons had signs of radiation-related morbidity . The trial was , therefore , discontinued prematurely 102 patients entered a multicentric r and omized study from May 1978 till December 1980 . After an operative removal of a supratentorial astrocytoma grade 3 or 4 all patients were treated by radiotherapy of the whole brain with 40 Gy , and after a rest of 1 to 2 weeks with a boost dose of 20 Gy to the tumor region . By r and omization the patients got misonidazole ( 400 mg/m2 ) to each of the 30 fractions or a placebo . The overall tolerance was good . A mild transient peripheral neuropathy was seen only in 2 patients . The median of survival time was not significantly different for both groups with 16 months ( grade 3 ) and 10 months ( grade 4 ) . Thus a radiosensitizing effect of misonidazole was not proven The Radiation Therapy Oncology Group ( RTOG ) and the Eastern Cooperative Oncology Group ( ECOG ) conducted a phase III trial in patients with malignant gliomas to evaluate 4 treatment arms : 1 ) 60 Gy to the whole brain ; 2 ) 60 Gy plus 10-Gy boost ; 3 ) 60 Gy plus carmustine ( BCNU ) ; and 4 ) 60 Gy plus semustine plus dacarbazine . Between September 1974 and March 1979 , 626 patients with malignant gliomas were treated on protocol RTOG 7401/ECOG 1374 . Each institution chose a subset of the treatments to which the patients would be r and omized . Patients were stratified according to subset and r and omized to the 4 treatment arms . There were no differences in survival among treatment arms . For patients greater than 60 years of age , the addition of chemotherapy to radiation therapy did not improve survival . For patients aged 40 - 60 years , there was a statistically significant increase in overall survival when BCNU was added to 60 Gy ( P less than .01 ) , with an increase in 2-year survival from 8 % to 23 % . This beneficial effect of BCNU is apparent in both histological groups ( astrocytoma with atypical or anaplastic foci and glioblastoma multiforme ) . Although few confirmatory autopsies are available , long-term survival in patients with astrocytomas with atypical and anaplastic foci who were treated with 60 Gy plus BCNU ( 5-yr survival , 22 % ) suggests no significant late CNS toxicity , compared to 60 Gy alone ( 5-yr survival , 15 % ) . This is confirmed by comparable neurological function in long-term survivors The results are reported of a small clinical trial carried out to assess the potential value of the hypoxic cell radiosensitizer misonidazole in the radiation treatment of Grade 3 and 4 supratentorial astrocytomas . A total of 55 patients were r and omly allocated to one of 3 treatment groups . No significant differences were seen between the median survivals of patients in the 2 control radiation groups and that of the third group in which oral misonidazole at a dose of 3 g/m2 preceded each of 4 weekly radiation doses . Possible reasons why no improvement was seen are discussed in detail PURPOSE To evaluate the efficacy and toxicity of accelerated radiotherapy in patients with primary high grade glioma , where acceleration is used as a means of delivering a shortened course of radical radiotherapy . PATIENTS AND METHODS Two-hundred and eleven patients with primary high grade glioma were treated at the Royal Marsden NHS Trust between 1987 and 1997 with accelerated radiotherapy ( 55 Gy in 34 fractions twice daily ) , to planning target volume ( PTV ) defined as enhancing tumour and a 3 cm margin . All had histologically confirmed high grade glioma ( 53 anaplastic astrocytoma , 137 glioblastoma multiforme , 4 gliosarcoma , 5 gemistocytic astrocytoma , 12 high grade astrocytoma not otherwise specified ) . The mean Karnofsky performance status ( KPS ) was 90 and median age was 54 years ( range 19 - 77 ) . RESULTS Of 211 patients entered , 201 were able to complete radiotherapy ; 39 patients ( 19 % ) had deterioration in KPS during radiotherapy and this was transient in 11 . Median survival of 211 patients was 10 months with 1 year , 2 year , and 3 year survival probabilities of 38 % , 14 % , and 8 % respectively . Age and extent of excision were independent prognostic factors for survival . Previous comparison to matched cohort receiving 60 Gy in 30 daily fractions did not demonstrate significant survival difference . CONCLUSION Accelerated radiotherapy is a feasible treatment approach for patients with high grade glioma . The survival and functional outcome are comparable to conventional radiotherapy and the treatment is without serious acute toxicity . While acceleration of conventional dose irradiation could be tested in r and omised studies , it is unlikely this approach would result in a clinical ly meaningful survival benefit . Accelerated radiotherapy therefore remains one of the ways of delivering radical irradiation in patients with high grade glioma . However , it adds complexity to what is a palliative treatment regimen and the rationale and advisability should be re-examined , particularly in terms of impact on quality of life , true patient preference , and health economic considerations Elderly patients with malignant glioma have a poorprognosis and the benefit of st and ard radical radiotherapyis equivocal . Twenty-two percent of the adult referralbase with malignant glioma at our centre isof age 70 years or greater . A phaseII study was undertaken to determine if ashorter course of therapy yields a comparable mediansurvival to radical radiotherapy and thus constitutes anappropriate investigational palliative regimen.25 patients were accrued between 1988–1995 , all ofwhom had histologically proven malignant glioma , 23 glioblastomamultiforme and 2 anaplastic astrocytoma . The median agewas 73 ( range 70–78 ) and median Karnofsky PerformanceStatus ( KPS ) was 70 . 40 % had a stereotacticbiopsy only for diagnosis . Radiotherapy was delivered tolimited fields to a dose of 37.5 Gyin 15 daily fractions over 3 weeks . Anintention-to-treat analysis was undertaken with survival determined from date of initial consultation . The median survival ofthe whole group was 8.0 months ( 95 % CI4.8–9.6 ) . Patients with good performance status ( KPS > 70 ) had a median survival of 10.4 months(95 % CI 9.6–14.7).37.5 Gy in 15 daily fractions appears toyield comparable median survival to that of otherseries of radical radiotherapy . A phase III study of this regimen is recommended in investigating optimalpalliation of elderly malignant glioma patients Recently , the RTOG and ECOG concluded a joint r and omized study on malignant gliomas that was in progress for the past five years . A total of 626 patients entered this protocol . Sixty‐seven percent of the 535 evaluable patients have died and thus this represents a preliminary report of a major joint clinical trial . The objective of this study was to evaluate the efficacy after neurosurgery of three new treatment options as compared with control treatment of radiotherapy alone . The four options were : ( 1 ) control radiation ; 6000 rad/6–7 weeks to whole brain ; ( 2 ) a higher radiation dose ; Control dose plus a booster dose of 1000 rad/1–2 weeks to the tumor ; ( 3 ) control radiation dose plus BCNU ( 80 mg/m2/day IV X 3 and repeat BCNU every 8 weeks ) ; ( 4 ) Control radiation dose plus combination methyl‐CCNU ( 125 mg/m2/day orally X 1 and repeat methyl‐CCNU every 8 weeks ) , and DTIC ( 150 mg/m2/day IV X 5 and repeat DTIC every 4 weeks ) . All pertinent patient characteristics were studied and several important prognostic factors have been identified . Notably , age , histologic type ( Astrocytoma with anaplastic foci , versus glioblastoma multiforme ) , initial performance status , time since first symptoms and presence or absence of seizure . At this time , it appeared that there was no treatment option which was significantly better than the control . The study identified that age was the most important prognostic factor . Patients who were younger than age 40 years had an 18‐month survival of 64 % , patients who were age 40–60 years had an 18‐month survival of 20 % , and patients who were older than age 60 had an 18‐month survival of 8 % . The study also demonstrated that a modified histologic classification of anaplastic astrocytoma versus glioblastoma provided better prognostic information than the astrocytoma grading system of Kernohan . Patients with anaplastic astrocytoma had a median survival of 27 months as compared to 8 months for patients with glioblastoma . In further evaluation of any beneficial effect of chemotherapy , it was identified that only among the 40–60‐year‐old groups , BCNU treated patients appeared to have significantly increased survival than patients in the control groups ( P = 0.01 , one‐sided ) . Similarly , methyl‐CCNU + DTIC was suggestively better than the control ( P = 0.08 , one‐sided ) . The higher radiation dose , 7000 rad/8–9 weeks appeared to give no significantly better survival over the control dose option . Both BCNU and methyl‐CCNU + DTIC produced some toxicity . The combination of methyl‐CCNU + DTIC was more toxic than BCNU , producing severe or worse thrombocytopenia in 23 % of the patients as compared to 6 % on BCNU In Brain Tumor Cooperative Group Study 77 - 02 , eleven institutions r and omized 603 adult patients with supratentorial malignant glioma to one of four treatment groups following surgery : conventional radiotherapy ( 6000 cGy in 30 - 35 fractions ) + BCNU , conventional radiotherapy + streptozotocin , hyperfractionated ( twice daily ) radiotherapy ( 6600 cGy in 60 fractions ) + BCNU , and conventional radiotherapy with misonidazole followed by BCNU . Data were analyzed for the total r and omized population and for the 557 patients ( 86 % with glioblastoma multiforme ) who met protocol eligibility specifications ( including confirmed histopathology on central review ) . Median survival was approximately 10 months following r and omization . Overall there was no statistically significant difference in survival among the four groups . Among non-glioblastoma patients , the misonidazole group appeared to have poor survival . Peripheral neuropathy was a dose-limiting toxicity with misonidazole . It is concluded that neither the addition of misonidazole nor hyperfractionated radiotherapy as given in this protocol offered any advantage over conventional radiotherapy plus either BCNU or streptozotocin for treatment of malignant glioma A total of 474 adult patients with malignant glioma ( astrocytoma ) grade 3 or 4 were r and omised into an MRC study ( BR2 ) comparing 45 Gy ( in 20 fractions over 4 weeks ) with 60 Gy ( in 30 fractions over 6 weeks ) of radiotherapy given post-operatively . Using 2:1 r and omisation , 318 patients were allocated the 60 Gy course and 156 the 45 Gy course . Adjuvant chemotherapy was not given . The results show that a 60 Gy course produces a modest lengthening of progression-free and overall survival . They suggest a statistically significant prolongation of median survival from 9 months in the 45 Gy group to 12 months in the 60 Gy group ( hazard ratio = 0.75 , chi 2 = 7.36 , d.f . = 1 , P = 0.007 ) . Over 80 % of patients reported no morbidity from the radiotherapy , and there was no evidence of increased short-term morbidity in the higher dose group . Late morbidity was not assessed . A prognostic index defined in a previous MRC study was vali date d in this new cohort . It identifies a group of patients ( 20 % of the total ) with a 2 year survival rate of 28 % ( 95 % confidence interval 19 % to 38 % ) . It was apparent that the survival advantage to the higher dose was maintained even in the poorest prognostic groups defined by this index A controlled , prospect i ve , r and omized study evaluated the use of 1,3-bis(2-chloroethyl)-1-nitrosourea ( BCNU ) and /or radiotherapy in the treatment of patients who were operated on and had histological confirmation of anaplastic glioma . A total of 303 patients were r and omized into this study , of whom 222 ( 73 % ) were within the Valid Study Group ( VSG ) , having met the protocol criteria of neuropathology , corticosteroid control , and therapeutic approach . Patients were divided into four r and om groups , and received BCNU ( 80 mg/sq m/day on 3 successive days every 6 to 8 weeks ) , and /or radiotherapy ( 5000 to 6000 rads to the whole brain through bilateral opposing ports ) , or best conventional care but no chemotherapy or radiotherapy . Analysis was performed on all patients who received any amount of therapy ( VSG ) and on the Adequately Treated Group ( ATG ) , who had received 5000 or more rads radiotherapy , two or more courses of chemotherapy , and had a minimum survival of 8 or more weeks ( the interval that would have been required to have received either the radiotherapy or chemotherapy ) . Median survival of patients in the VSG was , best conventional care : 14 weeks ( ATG : 17.0 weeks ) ; BCNU : 18.5 weeks ( ATG : 25.0 weeks ) ; radiotherapy : 35 weeks ( ATG : 37.5 weeks ) ; and BCNU plus radiotherapy : 34.5 weeks ( ATG : 40.5 weeks ) . All therapeutic modalities showed some statistical superiority compared to best conventional care . There was no significant difference between the four groups in relation to age distribution , sex , location of tumor , diagnosis , tumor characteristics , signs or symptoms , or the amount of corticosteroid used . An analysis of prognostic factors indicates that the initial performance status ( Karnofsky rating ) , age , the use of only a surgical biopsy , parietal location , the presence of seizures , or the involvement of cranial nerves II , III , IV , and VI are all of significance . Toxicity included acceptable , reversible thrombocytopenia and leukopenia A r and omized study investigating the value of misonidazole in patients irradiated for grade III and IV supratentorial astrocytomas was started in June 1977 . With a minimum follow-up time of 6 months , 45 patients who completed therapy are available for analysis . All patients received the same radiation treatment ( 66.5 Gy in 31 fractions over 7.5 weeks , field size reduction after 45 Gy ) . In the first , second and eighth week , a 4 Gy tumor dose was given on Monday and Thursday . Misonidazole was given 4 hours before irradiation to 18 r and omized patients on those 6 treatment days ( 2.1 - 2.7 g/m2 per treatment day ) . Daily tumor doses of 1.7 Gy were administered Monday through Friday from the third until the seventh week . Median survival for patients treated with misonidazole is 13.8 months ; for those treated by irradiation alone it was 9.8 months . The corresponding 1 year survival rates are 64 and 25 % , respectively . Survival plots indicate some advantage for the patients treated with misonidazole , however statistically there is no significant difference observed ( p greater than 0.08 ) . There are no significant differences in Karnofsky performance status , sex and in histological grade or in age distribution between the groups . However , the type of surgery ( complete or subtotal ) influenced survival markedly : patients with complete surgery lived significantly longer ( p less than 0.0009 ) . Neurotoxic side effects of misonidazole were minimal Between January 1977 and September 1980 , 166 patients were entered on a RTOG protocol comparing neutron-boost radiotherapy with st and ard treatment for patients with glioblastomas . Eighty-three patients were r and omized to receive a neutron boost and 83 to receive a photon boost after 50 Gy photon , whole-brain irradiation . Of these , six were ineligible and two were cancelled , leaving 158 patients available for analysis . The median survival for the neutron-boost group was 9.8 months , compared to 8.6 months for the photon-boost group . The difference is not statistically significant . Autopsies revealed actively growing persistent tumor in all photon-treated patients compared to no evidence of actively growing tumor in the majority of neutron-treated patients PURPOSE The purpose is twofold : ( 1 ) to identify the malignant glioma patients treated in a trial of hyperfractionated radiotherapy ( RT ) and carmustine ( BCNU ) who may have been eligible for a stereotactic radiosurgery ( SRS ) boost ; and ( 2 ) to compare survival of such patients with that of those considered SRS-ineligible . PATIENTS AND METHODS From January 1983 to July 1989 , 778 malignant glioma patients were enrolled on Radiation Therapy Oncology Group ( RTOG ) 83 - 02 , a r and omized phase I/II hyperfractionated RT dose-escalation trial with BCNU chemotherapy . The SRS criteria used in a single-institution trial were applied to these patients ; they are : Karnofsky performance status ( KPS ) of greater than 60 ; well-circumscribed tumor less than 4.0 cm ; no subependymal spread ; and a location not adjacent to brainstem or optic chiasm . RESULTS Eighty-nine patients ( 11.9 % ) were identified as potentially SRS-eligible . The median survival times ( MST ) and 18-month survival rates of the 89 eligible and 643 ineligible patients were 14.4 versus 11.7 months and 40 % versus 27 % , respectively ( P = .047 ) . The MST and 18-month survival rate of the 544 SRS-ineligible patients with KPS greater than 60 were 12.1 months and 29 % , respectively , and were not statistically inferior to the survival of the SRS-eligible group ( P = .21 ) . Multivariate analysis revealed age , KPS , and histopathology to be strongly predictive of survival , and SRS eligibility was also significantly predictive ( P = .047 ) . CONCLUSION SRS-eligible patients enrolled on RTOG 83 - 02 had survival superior to that of the SRS-ineligible group , and this advantage is mainly due to the selection of a subgroup with a high minimum KPS Multiple daily fractionated radiation therapy ( MDF ) may be more effective than conventionally fractionated radiation therapy ( CF ) in the treatment of malignant glioma . The hypoxic cell sensitizer misonidazole ( MISO ) could be more effective when employed with small fractions of radiation every 4 hours to take advantage of the long half-life of the drug . To evaluate MDF and MDF in combination with MISO , a r and omized prospect i ve trial was initiated . Between January 1981 , and December 1982 , patients with histologically verified astrocytoma with anaplastic foci or glioblastoma multiforme were r and omized to CF ( 5800 cGy , 30 fractions , 6 weeks ) , MDF ( 6141 cGy , 69 fractions , 4 1/2 weeks , at 89 cGy every 4 hours 3 times daily ) and MDF in combination with MISO ( 1.25 gm/M2 three times weekly for the first 3 weeks ) . In January 1983 , the CF arm was dropped and a high dose MDF arm added ( 7120 cGy , 80 fractions , 5 1/2 weeks , at 89 cGy per fraction every 4 hours 3 times daily ) . CCNU chemotherapy was given at the time of tumor progression . One hundred and twenty-eight patients were evaluated ( 38 CF , 42 MDF , 37 MDF plus MISO , and 11 high dose MDF ) . Median survival was 29 weeks for CF , 45 weeks for MDF and 50 weeks for MDF plus MISO . Survival was significantly improved for patients treated with MDF compared to patients treated with CF ( p less than .002 ) . The addition of MISO to MDF did not result in further improvement in survival . Acute toxicity was acceptable . No clinical ly apparent delayed toxicity was observed The effect of misonidazole on the duration of the free interval ( time to recurrence ) and total survival of adults bearing malignant supratentorial brain gliomas was measured in a r and omized double-blind study . Radiotherapy consisted of 9 X 3.5 Gy fractions given on alternate days during 3 weeks followed by 6 X 3-Gy fractions delivered in 2 weeks . Misonidazole , 1.3 g/m2 , administrated 4 hr before the 9 first irradiations to 82 patients , had no effect on the duration of the free interval or total survival compared with 81 controls . The two groups were comparable in respect to the main prognostic factors : median age , performance status or tumour location . The overall tolerance of misonidazole was good PURPOSE Older age and poor performance status at presentation are unfavorable prognostic factors for patients with glioblastoma multiforme . Some studies suggest a shorter , palliative course of radiotherapy may confer similar benefits as compared to a radical course in such patients . We report a prospect i ve , single arm trial , describing the use of a short-course of radiation in patients with glioblastoma and poor prognostic features . METHODS AND MATERIAL S Twenty-nine patients with pathologically confirmed glioblastoma and age > or = 65 years or with initial KPS < or = 50 were treated with a short-course of whole brain radiotherapy ( 30 Gy/10 fractions/2 weeks ) . Computer tomography tumor volume , dexamethasone requirements , Spitzer quality of life index , and Karnofsky performance status were measured pre and 1 month postradiation . Overall survival for the study patients was compared with that of radically treated and supportive care only historical controls . RESULTS Indices of tumor response were stable or improved in 60 % of patients evaluable 1 month postradiotherapy . Median survival for all study patients was 6 months . Median survivals in similar groups of radically treated and supportive care only patients were 10 and 1 month(s ) , respectively . A survival advantage for the radical vs. short-course treatment was observed for the subset of patients with a pretreatment KPS > 50 . CONCLUSION Elderly patients with a low pretreatment KPS ( < or = 50 ) may be treated adequately with a short , palliative course of radiotherapy . Elderly patients with a higher pretreatment KPS ( > 50 ) , however , may benefit from a higher dose radiotherapy regimen Within 3 weeks of definitive surgery , 571 adult patients with histologically confirmed , supratentorial malignant gliomas were r and omly assigned to receive one of three chemotherapy regimens : BCNU ( 1,3-bis(2-chloroethyl)-1-nitrosourea ) alone , alternating courses ( every 8 weeks ) of BCNU and procarbazine , or BCNU plus hydroxyurea alternating with procarbazine plus VM-26 ( epipodophyllotoxin ) . Patients accrued in 1980 and 1981 were to receive 6020 rads of whole-brain radiotherapy concurrent with the first course of chemotherapy . Patients accrued in 1982 and 1983 were r and omly assigned to receive either whole-brain irradiation as above , or 4300 rads of whole-brain radiotherapy plus 1720 rads coned down to to the tumor volume . The data were analyzed for the total r and omized population and separately for the 510 patients , termed the " Valid Study Group ( VSG ) , " who met protocol eligibility specifications ( including central pathology review ) , 80 % of whom had glioblastoma multiforme . The median survival times from time of r and omization for the three chemotherapy groups of the VSG ranged from 11.3 to 13.8 months , and 29 % to 37 % of the patients survived for 18 months ( life-table estimate ) ; the differences between these groups were not statistically significant . Survival differences between the radiotherapy groups were small and not statistically significant . It is concluded that , for malignant glioma , giving part of the radiotherapy by coned-down boost is as effective as full whole-brain irradiation , and that multiple-drug chemotherapy as outlined in this protocol conferred no significant survival advantage over BCNU alone Four hundred and thirty-six patients were treated between January 1979 and November 1981 in a double-blind r and omised study of the effect of the hypoxic cell sensitiser misonidazole ( Ro 07 - 0582 , MISO ) in conjunction with radiotherapy on grade s 3 and 4 astrocytoma . Radiotherapy was given in 20 fractions over 4 weeks to a minimum tumour dose of 4500 cGy . Misonidazole or placebo capsules were taken four to five hours before each radiotherapy treatment to a total dose of 11 - 13 g m-2 . Survival rates at 12 months , among the 384 eligible patients , were similar in the misonidazole treated patients ( 25 % ) and those receiving placebo ( 28 % ) . The estimated hazard ratio was 1.05 , indicating a slight disadvantage to misonidazole which was not statistically significant ( logrank test : chi 2 = 0.18 on 1 d.f . , p = 0.7 ) . Peripheral neuropathy was noted in 11 % of the misonidazole group and was mostly mild . Possible reasons for the failure to demonstrate any therapeutic gain from misonidazole are discussed OBJECTIVE During an 8-year interval , we evaluated the survival benefit of stereotactic radiosurgery performed in 64 patients with glioblastomas multiforme ( GBM ) and 43 patients with anaplastic astrocytomas ( AA ) . METHODS Adjuvant radiosurgery was performed either before disease progression or for recurrent tumor at the time of disease progression . Clinical and imaging follow-up data were obtained for all patients . The diagnosis of GBM was obtained by performing craniotomies in 41 patients and by performing stereotactic biopsies in 23 . The diagnosis of AA was obtained by performing craniotomies in 19 patients ( 44 % ) and by performing biopsies in 24 . RESULTS Of the entire series , the median survival time after initial diagnosis for patients with GBM was 26 months ( st and ard deviation [ SD ] , 19 mo ; range , 5 - 79 mo ) and the median survival time after radiosurgery was 16 months ( SD , 16 mo ; range , 1 - 74 mo ) . The 2-year survival rate was 51 % . No survival benefit was identified for patients who underwent intravenously administered chemotherapy in addition to radiosurgery ( P = 0.97 ) . After undergoing radiosurgery , 12 patients ( 19 % ) underwent craniotomies and resections and 4 ( 6 % ) underwent subsequent radiosurgery for regional or remote recurrence . For 45 patients who underwent radiosurgery as part of the initial management plan , the median survival time after diagnosis was 20 months . Of the entire series , the median survival time after diagnosis for patients with anaplastic astrocytomas was 32 months ( SD , 23 mo ; range 5 - 96 mo ) and the median survival time after radiosurgery was 21 months ( SD , 18 mo ; range 3 - 93 mo ) . The 2-year survival rate was 67 % . Ten patients ( 23 % ) underwent subsequent craniotomies at a mean of 8 months after initial surgery , and two underwent subsequent radiosurgery . There was no acute neurological morbidity after radiosurgery . Histologically proven radiation necrosis occurred in one patient with GBM ( 1.6 % ) and two patients with AA ( 4.7 % ) . For 21 patients for whom radiosurgery was part of the initial management plan , the median survival time after diagnosis was 56 months . CONCLUSION In comparison to historical controls , improved survival benefit after radiosurgery was identified for patients with GBM and patients with AA . Although this survival benefit may be related to our selection of patients for radiosurgery based on their having smaller tumor volumes , no selection was made based on location . We observed that radiosurgery was safe and well tolerated . Its effectiveness as an adjuvant therapy deserves a properly stratified r and omized trial The effectiveness and complications of radiation therapy for brain neoplasms are review ed . While the available data suggest a favorable influence and outcome , r and omized studies are needed to further optimize radiation therapy techniques and to integrate new therapeutic modalities PURPOSE This study attempted to compare within a r and omized study the outcome of pion radiation therapy vs. conventional photon irradiation for the treatment of high- grade astrocytomas . METHODS AND MATERIAL S Eighty-four patients were r and omized to pion therapy ( 33 - 34.5 Gy pi ) , or conventional photon irradiation ( 60 Gy ) . Entry criteria included astrocytoma ( modified Kernohan high Grade 3 or Grade 4 ) , age 18 - 70 , Karnofsky performance status ( KPS ) > or = 50 , ability to start irradiation within 30 days of surgery , unifocal tumor , and treatment volume < 850 cc . The high-dose volume in both arms was computed tomography enhancement plus a 2-cm margin . The study was design ed with the power to detect a twofold difference between arms . RESULTS Eighty-one eligible patients were equally balanced for all known prognostic variables . Pion patients started radiation 7 days earlier on average than photon patients , but other treatment-related variables did not differ . There were no significant differences for either early or late radiation toxicity between treatment arms . Actuarial survival analysis shows no differences in terms of time to local recurrence or overall survival where median survival was 10 months in both arms ( p = 0.22 ) . The physician-assessed KPS and patient-assessed quality of life ( QOL ) measurements were generally maintained within 10 percentage points until shortly before tumor recurrence . There was no apparent difference in the serial KPS or QOL scores between treatment arms . CONCLUSION In contrast to high linear energy transfer ( LET ) therapy for central nervous system tumors , such as neutron or neon therapy , the safety of pion therapy , which is of intermediate LET , has been reaffirmed . However , this study has demonstrated no therapeutic gain for pion therapy of glioblastoma PURPOSE A r and omized study was undertaken to assess the role of brachytherapy as a boost to external beam radiation therapy in the initial management of patients with malignant astrocytomas . METHODS AND MATERIAL S Inclusion criteria included the following : biopsy-proven supratentorial malignant astrocytoma of brain < or = 6 cm in size , not crossing midline or involving corpus callosum , age 18 - 70 , Karnofsky Performance Status ( KPS ) > or = 70 . Patients were r and omized to external radiation therapy only delivering 50 Gray ( Gy ) in 25 fractions over 5 weeks or external radiation therapy plus a temporary stereotactic iodine-125 implants delivering a minimum peripheral tumor dose of 60 Gy . Patients were stratified to age < or = 50 or > 50 , and KPS > or = 90 or < or = 80 . RESULTS There were 140 patients r and omized between 1986 and 1996 , 71 to the implant arm and 69 to external irradiation only . Pathologically 125 patients had necrosis noted in their tumor specimen . Factors associated with improved survival in univariate analysis were age < or = 50 , KPS > or = 90 , chemotherapy at recurrence , and reoperation at the original tumor site . The Cox proportional hazards model revealed the following significant factors : treatment at recurrence ( chemotherapy or reoperation ) with a relative risk ( RR ) of 0.6 ( p = 0.004 ) and KPS > or = 90 with a RR 0.6 ( p = 0.007 ) . R and omization to the implant arm was associated with a RR of 0.7 ( p = 0.07 ) . Median survival for patients r and omized to brachytherapy or not were 13.8 vs. 13.2 months , respectively , p = 0.49 . CONCLUSIONS We conclude that stereotactic radiation implants have not demonstrated a statistically significant improvement in survival in the initial management of patients with malignant astrocytoma PURPOSE To evaluate the efficacy and toxicity of a stereotactic radiosurgery boost as part of the primary management of a minimally selected population of patients with malignant gliomas . METHODS AND MATERIAL S Between June , 1991 and January , 1994 a stereotactic radiosurgery boost was given to 30 patients after completion of fractionated external beam radiotherapy . The study population consisted of 22 males and 8 females , with a range in age at treatment from 5 to 74 years ( median : 54 years ) . Tumor volume ranged from 2.1 to 115.5 cubic centimeters ( cc ) ( median : 24 cc ) . Histology included 17 with glioblastoma multiforme , 10 with anaplastic astrocytoma , 1 with a mixed anaplastic astrocytoma-oligodendroglioma , and 2 with a gliosarcoma . A complete resection was performed in 9 ( 30 % ) patients , while 18 ( 60 % ) underwent a subtotal resection , and 3 ( 10 % ) received a biopsy only . Fractionated radiation dose ranged from 44 to 62 Gy , with a median of 59.4 Gy . Prescribed stereotactic radiosurgery dose ranged from 0.5 to 18 Gy ( median : 10 Gy ) , and the volume receiving the prescription dose ranged from 2.1 to 158.7 cc ( median : 46 cc ) . The volume of tumor receiving the prescription dose ranged from 70 - 100 % ( median : 100 % ) . One to four ( median : 2 ) isocenters were used , and collimator size ranged from 12.5 to 50 mm ( median size : 32.5 mm ) . The median minimum stereotactic radiosurgery dose was 70 % of the prescription dose and the median maximum dose was 200 % of the prescription dose . RESULTS With a minimum follow-up of 1 year from radiosurgery , 7 ( 23 % ) of the patients are still living and 22 ( 73 % ) have died of progressive disease . One patient died of a myocardial infa rct ion 5 months after stereotactic radiosurgery . Follow-up for living patients ranged from 12 to 45 months , with a median of 30 months . The 1- and 2-year disease-specific survival from the date of diagnosis is 57 [ 95 % confidence interval ( CI ) 39 to 74 % ] and 25 % ( 95 % CI 9 to 41 % ) , respectively ( median survival : 13.9 months ) . No significant acute or late toxicity has been observed . CONCLUSION Stereotactic radiosurgery provides a safe and feasible technique for dose escalation in the primary management of unselected malignant gliomas . Longer follow-up and a r and omized prospect i ve trial is required to more thoroughly evaluate the role of radiosurgery in the primary management of malignant gliomas A prospect i ve r and omized trial of 157 patients with malignant astrocytoma ( Grade III or IV ) was carried out at a single institution . The minimization technique ensured balanced distribution of prognostic factors between the treatment groups . All received oral lomustine ( CCNU , 80 mg/m2 ) six weekly and hydroxyurea ( HU , 3.5 gm/m2 over 5 days ) three weekly , for one year or until recurrence , with doses adjusted for myelosuppression . Patients were r and omized to daily ( 5000 rad in 25 fractions ( fr ) in 5 weeks ) or Q3h ( every 3 hours ) Cobalt 60 irradiation ( 3600–4000 rad in 36–40 fr of 100 rad each , given 4 fr per day at 3‐hour intervals over two weeks ) Steroid therapy ( up to 16 mg day dexamethasone ) was permitted . Complications were moderate and equivalent in the two groups . No significant survival or toxicity differences were seen between the two groups . Age , initial performance status , and extent of surgical resection were found to be significant ( P < 0.01 ) prognostic factors for survival . Median survival of the whole group was 48 weeks with a minimum follow‐up of one year . There was no advantage to large radiation fields . The hyperfractionation and daily regimes had similar efficacy and toxicity . Hyperfractionation with chemotherapy offers a useful alternative approach in the management of this disease The authors undertook a controlled , prospect i ve , r and omized study of 171 patients with supratentorial astrocytoma Grade s 3 and /or 4 ( classified according to Kernohan ) . All patients were given chemotherapy consisting of procarbazine , vincristine , and lomustine ( CCNU ) ( PVC ) . Half of the patients received whole‐brain irradiation ( RT ) to a dose of 5800 cGy in the tumor‐bearing hemisphere and 5000 cGy in the contralateral hemisphere . After diagnosis of progressive tumor growth , patients received individual treatment . The endpoint of the study was time to progression , but cases were followed until the patients died . Median time to progression ( MTP ) for the whole r and omized population was 21 weeks . Median survival time ( MST ) was 53 weeks ; 18 % of patients survived for 2 years or longer . Survival analysis showed that patients less than 50 years of age treated with PVC plus RT had significantly longer MTP ( 81 weeks ) and MST ( 124 weeks ) than all other patients . For patients less than 50 years of age treated with PVC alone , MTP was 21 weeks and MST was 66 weeks . For patients more than 50 years of age treated with PVC plus RT , MTP was 23 weeks and MST was 51 weeks ; in the PVC group , MTP was 17 weeks and MST was 39 weeks . Age , Karnofsky index , areas of Grade 2 , and absence of extensive necrosis in the tumor were significant prognostic factors in the univariate analyses . Patients less than 50 years of age treated with PVC plus RT had significantly longer survival ( P = 0.037 ) when correcting for these factors in a multi‐variate analysis PURPOSE Median survival of patients with glioblastoma multiforme ( GBM ) is only about 4 months with surgery and about 9 months for surgery followed by radiotherapy . Prolonged treatment is futile for many patients and the time of treatment and hospitalization should be minimized . METHODS AND MATERIAL S This was a prospect i ve , nonr and omized study of 30 patients treated with a hypofractionated radiation scheme ( 42 Gy in 14 fractions ) . RESULTS Median survival was 36 weeks . Age , Karnofsky performance status ( KPS ) and extent of surgery were strongly interrelated and all correlated with survival ( p < 0.05 ) . Three prognostic groups were identified . Patients with three favorable prognostic factors ( age < 50 , KPS 80 - 100 , and > or = 75 % of the tumor removed ) had the best prognosis ( median survival 50 weeks ) . Patients with no favorable prognostic factors ( age > or = 50 , KPS < or = 70 , and < 75 % of the tumor removed ) had the worst prognosis ( median survival 25 weeks ) . Median survival of the intermediate group ( with one or two favorable prognostic factors ) was 38 weeks . No severe acute or late toxicity was observed . CONCLUSION The treatment results are comparable to those achieved with conventional radiotherapy schemes . Based on the number of favorable prognostic factors ( age < 50 , KPS 80 - 100 and > or = 75 % of tumor resected ) the radiation schedule should be selected OBJECTIVE To assess the feasibility , toxicity , and local control of stereotactic radiosurgery followed by accelerated external beam radiotherapy ( AEBR ) for patients with glioblastoma multiforme . MATERIAL S AND METHODS Six males and eight females , with a median age of 67.5 years ( range 45 - 78 years ) , entered the study . Karnofsky performance status was 90 for five , 80 for six , and 60 for three patients . Following surgery , the patients were left with a residual mass 4 cm . Radiosurgery was delivered with a single dose of 20 Gy to the 90 % isodose surface corresponding to the contrast-enhancing edge of the tumour . A total AEBR dose of 60 Gy in 30 fractions was delivered using a concomitant boost technique over four weeks . RESULTS Median survival time was 40 weeks ( range 17 - 80 weeks ) . Actuarial survivals at 12 and 18 months were 43 % and 14 % , respectively . The median time to progression was 25 weeks ( range 2 - 77 weeks ) . One patient developed a seizure on the day of stereotactic radiosurgery . Two patients experienced somnolence at 47 and 67 days post-radiotherapy . Eight patients remained steroid-dependent . Radiological evidence of leukoencephalopathy was observed in one patient , and brain necrosis in two additional patients at 30 and 63 weeks . One of these two patients with brain necrosis developed complete loss of vision in one eye , and decreased vision in the contralateral eye at 63 weeks . CONCLUSION Stereotactic radiosurgery followed by AEBR was feasible but was associated with late complications . The use of such radiosurgical boost for patients with glioblastoma multiforme should be reserved for those patients entering controlled clinical trials Preliminary results of superfractionation in the treatment of glioblastoma led to a r and omized trial consisting of 76 patients . All patients received whole brain irradiation followed by a 1000 cGy boost to the primary site . Thirty-four patients received st and ard daily treatment to 4000 cGy , whereas 42 patients received superfractionated radiation , treating three times a day to a total dose of 4760 cGy . No significant difference was found between the 5-year survival of the superfractionated group and the st and ard treatment group . Early reactions were greater for superfractionation whereas late effects were less Background . A Phase I/II r and omized dose‐seeking trial was performed to document the severity , time course , and significance of white matter changes seen on serial imaging scans ( magnetic resonance imaging , computed tomography ) associated with bis‐chlorethyl nitrosourea ( BCNU ) and hyperfractionated cranial irradiation A material of 108 patients with glioblastoma is presented . The series was r and omized in two groups : cases only operated upon and cases with postoperative irradiation in addition . Patients dead within 2 months after operation were excluded in estimating the real value of the postoperative irradiation . The irradiated cases had a 6-month survival rate of 64 per cent and a one-year survival rate of 19 per cent ; the non-irradiated cases a 6-month survival rate of 28 per cent and a one-year survival rate of 0 per cent Between January 1983 and November 1987 , the Radiation Therapy Oncology Group conducted a prospect i ve , r and omized , multi-institutional , dose search ing Phase I/II trial to evaluate hyperfractionated radiation therapy in the treatment of supratentorial malignant glioma . Patients with anaplastic astrocytoma , or glioblastoma multiforme , age 18 - 70 years with a Karnofsky performance status of 40 - 100 were stratified according to age , Karnofsky performance status , and histology , and were r and omized . Initially r and omization was to one of three arms : 64.8 Gy , 72.0 Gy , and 76.8 Gy . Fractions of 1.2 Gy were given twice daily , 5 days per week , with intervals of 4 to 8 hr . All patients received bis-chlorethyl nitrosourea ( BCNU ) 80 mg/m2 on days 3 , 4 , 5 of radiation therapy and then every 8 weeks for 1 year . After acceptable rates of acute and late effects were found , the r and omization was changed to 81.6 Gy and 72.0 Gy with a weighting of 2:1 . Out of 466 patients r and omized , 435 were analyzed . The distribution of prognostic factors was comparable among the 76.8 Gy arm , 81.6 Gy arm , and the final r and omization of the 72 Gy arm . The 64.8 Gy arm and the initial r and omization of the 72 Gy arm had somewhat worse prognostic variables . Late radiation toxicity occurred in 1.3 - 6.8 % of the patients , with a modest increase with increasing radiation dose . The best survival occurred in those patients treated with 72 Gy ( median survival of 12.8 months overall , and 14 months for the final 72 Gy r and omization ) . The Cox proportional hazards model confirmed the prognostic variables of age , histology and Karnofsky performance status . In addition , the longer interval of 4.5 - 8 hr was associated with a worse prognosis than the 4 - 4.4 hr interval ( p = 0.0011 ) . The difference in survival between the 81.6 Gy arm and the lower three arms approached significance ( p = 0.078 ) with inferior survival observed in the 81.6 Gy arm . When therapy was evaluated by radiation therapy dose received ( 60 - 74.4 Gy compared with 74.5 - 84.0 Gy ) , the p value was 0.062 in favor of the lower dose range . Patients with anaplastic astrocytoma treated with 72 Gy by hyperfractionation + BCNU had at least as good a survival as those treated with 60 Gy by conventional fractionation + BCNU on Radiation Therapy Oncology Group protocol s 7401 and 7918 . This suggests that 72 Gy delivered by 1.2 Gy twice daily is no more toxic than 60 Gy delivered by conventional fractionation This r and omized RTOG study evaluated misonidazole radiosensitized radiation therapy in the treatment of malignant glioma . One hundred and forty-six evaluable patients were treated with conventional radiation therapy to 60.00 Gy in 6 - 7 weeks plus BCNU 80 mg/m2/d for 3 days every 8 weeks ( XRT + BCNU ) . One hundred and forty-seven evaluable patients were treated with misonidazole 2.5 gm/m2 once a week for 6 weeks , radiation therapy to 60 Gy and BCNU ( MISO + XRT + BCNU ) . Patients were stratified according to the prognostic factors of age , performance status , and histology . Distribution of these characteristics was comparable among the treatment groups . The median survival for XRT + BCNU was 55.0 weeks , and for MISO + XRT + BCNU 46.0 weeks ( p = 0.35 ) . With patients on a minimum dose of dexamethasone of 3 mg/d , misonidazole neurotoxicity included 8.8 % peripheral neuropathy , 2.7 % CNS toxicity , and a 0.68 % ototoxicity . BCNU pulmonary toxicity occurred in 9.3 % of patients who received 902 - 2062 mg/m2 of BCNU A r and omised trial is reported of mixed-schedule ( neutron/photon ) irradiation compared with photon therapy for patients with Grade III or Grade IV astrocytoma . Thirty-one patients were allocated to be treated by the neutron/photon regime and 30 patients by photons . The median survival was 4 months in the mixed-schedule group and 8 months in the photon group . The survival rates were not significantly different . All patients who died had evidence of residual brain tumour . None had signs of radiation-related morbidity PURPOSE This study was an open label , r and omized Phase 3 trial in newly diagnosed patients with anaplastic glioma comparing radiotherapy plus adjuvant procarbazine , CCNU , and vincristine ( PCV ) chemotherapy with or without bromodeoxyuridine ( BUdR ) given as a 96-hour infusion each week of radiotherapy . METHODS AND MATERIAL S Only patients 18 years or older with newly diagnosed anaplastic glioma were eligible ; central pathology review was accomplished , but was not m and ated prior to registration . The study had initially opened as a Northern California Oncology Group ( NCOG ) trial in 1991 , becoming an Intergroup RTOG , SWOG , and NCCTG study in July 1994 . Total accrual of 293 patients was planned as the sample size , using survival and time to tumor progression as the primary endpoints . The experiment arm ( RT/BUdR plus PCV ) was to be compared to the control arm ( RT plus PCV ) using an alpha = 0.05 , one-tailed , with a power of 85 % for detecting an increase in median survival from 160 to 240 weeks , assuming a 3-year follow-up after completion of enrollment . RESULTS As of July 1996 , 281 patients had been r and omized ; 53 ( 20 % ) were ineligible , primarily based upon central pathology review , and another 39 cases were canceled . In total , 30 % of cases were excluded from analysis . The treatment arms were well balanced despite this rate of exclusion . The RTOG Data Monitoring Committee recommended suspension of enrollment in July 1996 based upon a stochastic curtailment analysis which strongly suggested that the addition of BUdR would not be associated with increased survival . In February 1997 , the study was closed prior to full enrollment . At that time , the 1-year survival estimates were 82 % versus 68 % for RT plus PCV and RT/BUdR plus PCV respectively ( one-sided , p = 0.96 ) . The conditional power analysis indicated that even with an additional 12 months of additional accrual and follow-up the probability of detecting the prespecified difference was less than 0.01 % . The differences in the two arms seem to be due to early deaths in the BUdR arm , not related to toxicity of the treatment . CONCLUSIONS Despite encouraging Phase 2 results with BUdR , it is unlikely that a survival benefit will be seen . A final study analysis will not be done for at least 3 more years BACKGROUND Despite notable technical advances in therapy for malignant gliomas during the past decade , improved patient survival has not been clearly documented , suggesting that pretreatment prognostic factors influence outcome more than minor modifications in therapy . Age , performance status , and tumor histopathology have been identified as the pretreatment variables most predictive of survival outcome . However , an analysis of the association of survival with both pretreatment characteristics and treatment-related variables is necessary to assure reliable evaluation of new approaches for treatment of malignant glioma . PURPOSE This study of malignant glioma patients used a non-parametric statistical technique to examine the associations of both pretreatment patient and tumor characteristics and treatment-related variables with survival duration . This technique was used to identify subgroups with survival rates sufficiently different to create improvements in the design and stratification of clinical trials . METHODS We used a recursive partitioning technique to analyze survival in 1578 patients entered in three Radiation Therapy Oncology Group malignant glioma trials from 1974 to 1989 that used several radiation therapy ( RT ) regimens with and without chemotherapy or a radiation sensitizer . This approach creates a regression tree according to prognostic variables that classifies patients into homogeneous subsets by survival . Twenty-six pretreatment characteristics and six treatment-related variables were analyzed . RESULTS The years ) . Patients younger than 50 years old were categorized by histology ( astrocytomas with anaplastic or atypical foci [ AAF ] versus glioblastoma multiforme [ GBM ] ) and subsequently by normal or abnormal mental status for AAF patients and by performance status for those with GBM . For patients aged 50 years or older , performance status was the most important variable , with normal or abnormal mental status creating the only significant split in the poorer performance status group . Treatment-related variables produced a subgroup showing significant differences only for better performance status GBM patients over age 50 ( by extent of surgery and RT dose ) . Median survival times were 4.7 - 58.6 months for the 12 subgroups result ing from this analysis , which ranged in size from 32 to 256 patients . CONCLUSIONS This approach permits examination of the interaction between prognostic variables not possible with other forms of multivariate analysis . IMPLICATION S The recursive partitioning technique can be employed to refine the stratification and design of malignant glioma trials Various attempts have been made to improve the effectiveness of radiation in the treatment of cerebral malignant astrocytomas . A trend favoring multiple daily fractionated ( MDF ) radiation therapy over conventional single daily fractionated ( CF ) radiation therapy was identified in our previous study . In order to assess the effect of MDF with and without misonidazole , a province‐wide prospect i ve r and omized trial was initiated in January 1981 . By March 1984 , 124 patients with histologically verified grade III and IV astrocytomas were r and omized to CF ( 5800 cGy/6 weeks/30 fractions ) MDF ( 6141 cGy/4.5 weeks/69 fractions at 89 cGy every 3–4 hours , three times a day ) and MDF in combination with misonidazole ( 1.25 g/m2 three times weekly for the first 3 weeks ) . Thirty‐eight patients were r and omized to CF , 43 patients to MDF , and 43 patients to MDF and misonidazole . At the preliminary assessment in July 1984 , the median survival time was 27 weeks for the CF group , 39 weeks for the MDF group and 49 weeks for MDF and misonidazole group . The 1‐year actuarial survival rate from surgery was 20 % for CF group , 41 % for MDF group , and 45 % for MDF and misonidazole group . There is a statistically significant difference ( P < 0.001 ) between the CF and MDF group . However , the addition of misonidazole does not significantly alter survival From September 1980 through January 1985 , the Radiation Therapy Oncology Group ( RTOG ) conducted a r and omized , dose- search ing study testing the efficacy of a concomitant neutron boost along with whole brain photon irradiation in the treatment of malignant gliomas of the brain . Patients had to have biopsy-proven , supratentorial , anaplastic astrocytoma or glioblastoma multiforme ( Nelson schema ) to be eligible for the study . The whole brain photon irradiation was given at 1.5 Gy per treatment , 5 days-a-week to a total dose of 45 Gy . Two days-a-week the patients were to receive neutron boost irradiation to the tumor volume as determined on CT scans . The neutron irradiation was to be given prior to and within 3 hours of the photon irradiation on that day . The rationale for this particular treatment regime is discussed . A total of 190 evaluable patients were r and omized among 6 different neutron dose levels : 3.6 , 4.2 , 4.8 , 5.2 , 5.6 and 6.0 Gyn gamma . There was no difference in overall survival among the 6 different dose levels , but for patients having less aggressive tumor histology ( anaplastic astrocytoma ) , there was a suggestion that patients on the higher dose levels had poorer overall survival than patients on the lower dose levels and also did worse than historical photon controls . Important prognostic factors were identified using a Cox stepwise regression analysis . Tumor histology , Karnofsky performance status , and patient age were found to be related to survival while extent of surgery and neutron dose had no significant impact . Autopsies were performed on 35 patients and the results correlated with the actual neutron dose as determined by central -axis isodose calculations . At all dose levels there were some patients with both radiation damage to normal brain tissue and evidence of viable tumor . No evidence was found for a therapeutic window using this particular treatment regimen PURPOSE To determine if adjuvant interstitial hyperthermia ( HT ) significantly improves survival of patients with glioblastoma undergoing brachytherapy boost after conventional radiotherapy . METHODS AND MATERIAL S Adults with newly-diagnosed , focal , supratentorial glioblastoma < or = 5 cm in diameter were registered postoperatively on a Phase II/III r and omized trial and treated with partial brain radiotherapy to 59.4 Gy with oral hydroxyurea . Those patients whose tumor was still implantable after teletherapy were r and omized to brachytherapy boost ( 60 Gy at 0.40 - 0.60 Gy/h ) + /- HT for 30 min immediately before and after brachytherapy . Time to progression ( TTP ) and survival from date of diagnosis were estimated using the Kaplan-Meier method . RESULTS From 1990 to 1995 , 112 eligible patients were entered in the trial . Patient ages ranged from 21 - 78 years ( median , 54 years ) and KPS ranged from 70 - 100 ( median , 90 ) . Most commonly due to tumor progression or patient refusal , 33 patients were never r and omized . Of the patients , 39 were r and omized to brachytherapy ( " no heat " ) and 40 to brachytherapy + HT ( " heat " ) . By intent to treat , TTP and survival were significantly longer for " heat " than " no heat " ( p = 0.04 and p = 0.04 ) . For the 33 " no heat " patients and 35 " heat " patients who underwent brachytherapy boost , TTP and survival were significantly longer for " heat " than " no heat " ( p = 0.045 and p = 0.02 , respectively ; median survival 85 weeks vs. 76 weeks ; 2-year survival 31 % vs. 15 % ) . A multivariate analysis for these 68 patients adjusting for age and KPS showed that improved survival was significantly associated with r and omization to " heat " ( p = 0.008 ; hazard ratio 0.51 ) . There were no Grade 5 toxicities , 2 Grade 4 toxicities ( 1 on each arm ) , and 7 Grade 3 toxicities ( 1 on " no heat " and 6 on the " heat " arm ) . CONCLUSION Adjuvant interstitial brain HT , given before and after brachytherapy boost , after conventional radiotherapy significantly improves survival of patients with focal glioblastoma , with acceptable toxicity Abstract In a r and omized trial , 134 patients suffering from Glioblastoma Multiforme were r and omly assigned to three radiation treatment schedules wherein patients were treated at S hr or 24 hr intervals over a period of 1 week or 3 weeks , initially receiving 3000 rad TD ¶ ¶TD , Tumor dose . and subsequently 4000 rad TD . There were no significant differences in immediate or delayed complications amongst the various groups . Survival was not significantly different in the various study groups , and was not influenced by the patient 's age and sex , the extent of surgery or the tumor grade From February 1989 to December 1992 , 31 patients who presented with an initial pathological diagnosis of glioblastoma multiforme underwent tumor debulking or biopsy , stereotactic radiosurgery , and st and ard radiation therapy as part of their primary treatment . Presenting characteristics in the 22 men and nine women included a median age of 57 years , Karnofsky Performance Scale score median of 80 , and median tumor volume of 16.4 cm3 . Stereotactic radiosurgery delivered a central dose of 15 to 35 Gy with the isocenter location , collimator size , and beam paths individualized by means of three-dimensional software developed at the University of Wisconsin . The peripheral isodose line varied from 40 % to 90 % with a median of 72.5 % and a mode of 80 % . The mean follow-up period was 12.84 months with a median of 9.5 months . Statistical analysis was performed using Kaplan-Meier analysis and log-rank comparison of risk factor groups . The parameters of age , initial Karnofsky Performance Scale score , and biopsy were significantly different in patient survival from debulking ; but no difference was noted between single and multiple isocenters and patterns of steroid requirement . Radiographic recurrences were divided by location into the following categories : central ( within central stereotactic radiosurgery dose ) , 0 ; peripheral ( within 2 cm of central dose ) , 19 ; and distant ( > 2 cm ) , 4 . There is no evidence of recurrence in five surviving patients . Actuarial 12-month survival was 37 % , with a median survival of 9.5 months . These values are similar to previous results for surgery and st and ard radiotherapy alone . The results suggest that the curative value of radiosurgery is significantly limited by peripheral recurrences Prospect i ve r and omized clinical study was conducted to evaluate the factor of radiation field in radiotherapy for malignant glioma from 1981 to 1988 at Tokyo Women 's Medical College . Radiation methods were r and omized to two groups ; ( I ) whole brain ( 40 Gy ) and local irradiation ( 18 Gy ) , total dose 58 Gy/29 f/6 weeks ( TDF 91 ) , ( II ) local irradiation , total 56 Gy/28 f/6 weeks ( TDF 90 ) . Twenty three cases were registered as group I and 26 cases as group II . Two and four years cumulative survival rate were 43 % and 17 % in group I and 39 % and 27 % in group II . There were no significant differences on response , survival , recurrent pattern , late effect and complications between whole brain and local irradiation . This study confirmed that local control was the most important in the treatment of malignant glioma The purpose of this pilot study was to determine the feasibility and toxicities of an accelerated treatment program by using a concomitant stereotactic radiotherapy boost given weekly during a course of st and ard external-beam irradiation ( EBXRT ) in patients with malignant gliomas . Twelve patients underwent biopsy or subtotal resection of a malignant glioma and were enrolled on the protocol , which delivered 44 Gy-EBXRT and a 12-Gy stereotactic radiotherapy boost given on 3 consecutive weeks of treatment for a total dose of 80 Gy over 33 days . Three patients with anaplastic astrocytoma and nine patients with glioblastoma multiforme had median survival times of 33 months and 16 months , respectively . All of the tumor recurrences were within or were closely adjacent to the region of high-dose irradiation . None of the patients required a treatment break , and there were no acute complications . Two patients developed seizures in the follow-up period , and four patients were diagnosed with radionecrosis at the time of the second operation . The treatment program was found to be feasible and was well tolerated , and it result ed in a rate of late complications similar to those of radiosurgery or interstitial brachytherapy Superfractionation ( SF ) radiation therapy is the administration of three fractions per day . We have assessed the effect of SF in a prospect i ve r and omized clinical study of malignant astrocytomas from July 1978 to December 1980 . Thirty-five patients were r and omized to SF ( 4000 rad in 45 fractions in 3 weeks whole brain and 1000 rad in five fractions in one week local boost ) . Thirty-four patients were r and omized to conventional fractions ( 3400 rad in 17 fractions whole brain in 3.5 weeks and 1600 rad in eight fractions in 1.5 weeks local boost ) . Both treatment arms received chemotherapy with CCNU . The 1- and 2-year actuarial survival rate is 54 % and 21 % for SF group and 32 % and 10 % for CF group . The other advantages of SF include shorter mean duration of steroid administration and improved performance status following radiation therapy PURPOSE Prospect i ve evaluation of the toxicity and efficacy of radiosurgery with external beam radiotherapy in the management of newly diagnosed glioblastoma . METHODS AND MATERIAL S From 5/89 to 12/92 , 31 out of 51 patients with glioblastoma multiforme underwent radiosurgery , in addition to 54 Gy in 1.8 Gy/fraction following biopsy ( n = 12 ) or resection ( n = 19 ) . Eligibility required supratentorial glioblastoma , tumor not > 4 cm in > 1 axis , age > 18 years , and location > 1 cm from optic chiasm . Patient characteristics were : age 20 - 78 years ( median = 57 ) ; 22 male , 9 female ; Karnofsky score 20 - 90 ( m = 70 ) , and volume of 2.3 - 59.7 c.c . ( m = 17.4 ) . Eighteen patients were treated with 1 collimator , 5 with 2 , 7 with 3 , and 1 with 4 ; peripheral isodoses were 40 - 90 % ( m = 72.5 ) and minimum and maximum tumor dose ranges were 10 - 20 ( m = 12 ) and 15 - 35 Gy ( m = 18.75 ) . Patients were followed clinical ly and radiographically every 8 - 12 weeks to analyze survival , quality of life , and toxicity . RESULTS With a follow-up of 12 - 171 weeks , 8 out of 31 ( 26 % ) patients are alive . Median survival is 42 weeks . Twelve and 24-month actuarial survival are 38 and 28 % . Comparison of the 2-year survival with previous Radiation Therapy Oncology Group patients was carried out using a nonparametric recursive partitioning technique and the observed vs. expected values are 28 vs. 9.7 % ( p < 0.05 ) . Extent of resection and performance status were associated with improved survival in a multivariate analysis . No significant acute toxicity was encountered . Four patients ( 13 % ) developed clinical ly significant necrosis verified by biopsy or positron emission tomography scan at 9 - 59 weeks after radiosurgery . CONCLUSION The improvement in median survival in broadly selected glioblastoma patients treated with radiosurgery is difficult to determine , but the 2-year survival may be superior . Future r and omized trials of radiosurgery are recommended , and ad hoc use of this modality should be discouraged The RTOG has sponsored several studies for malignant gliomas of the brain that have included tumors classified as either glioblastoma multiforme ( GBM ) or anaplastic-atypical astrocytoma ( AAF ) under the Nelson schema . Glioblastoma multiforme , the more aggressive histology , has done poorly under all forms of treatment having a typical median survival of 8 - 11 months . The less common and less aggressive anaplastic-atypical astrocytoma seems to show a survival that worsens with treatment more aggressive than st and ard radiotherapy . All patients in this report have had their tumors central ly review ed by a RTOG neuropathologist and have had the diagnosis of anaplastic-atypical astrocytoma confirmed . We compare three patient groups : st and ard photon radiotherapy from the 60 and 70 Gy arms of RTOG 74 - 01/ECOG 1374 and from the 65 Gy control arm of RTOG 76 - 11 ; radiation therapy and chemotherapy from RTOG 74 - 01/ECOG 1374 ( 60 Gy + BCNU and 60 Gy + MeCCNU + DTIC ) and from RTOG 79 - 18 ( 60 Gy + BCNU ) ; and photon irradiation plus a neutron boost from RTOG 76 - 11 and RTOG 80 - 07 . There are 47 analyzable cases treated with photons alone , 78 analyzable cases treated with photons + chemotherapy , and 38 analyzable cases treated with photons + neutron boost . Median survival for the three groups of patients is , respectively , 3.0 years , 2.3 years , and 1.7 years . Actuarial survival curves are presented for each subgroup of patients and then for the patient subgroups further broken down by major prognostic variables -- age and Karnofsky performance status . In each " better prognostic category , " the median survival decreased as the " aggressiveness " of the treatment increased . The implication s of these findings for future clinical trials is discussed In a controlled , prospect i ve , r and omized investigation , started in 1974 , 118 patients with supratentorial astrocytoma Grade III – IV were divided into three groups . Groups 1 and 2 received 45 Gy postoperatively to the whole supratentorial brain . Bleomycin in 15‐mg doses and a total dose of 180 mg or placebo was given intravenously three times a week , one hour prior to radiotherapy , during weeks 1,2,4 and 5 . Group 3 received conventional care but no radiotherapy or chemotherapy . Median survival rates of patients were 10.8 months in Groups 1 and 2 , and 5.2 months in Group 3 , a statistically significant difference . With regard to performance , the patients in Group 3 deteriorated faster than patients in Groups 1 and 2 . Bleomycin had no positive or negative influence on survival Thirty-three patients with malignant glioma were r and omly divided into two groups after extensive tumor resection . Those in group A received , every five to eight weeks , a course of chemotherapy consisting of intravenously administered carmustine , 80 mg/sq m/day for three days , and vincristine sulfate , 1.4mg/sq m on days 1 and 8 . Patients in group B were treated identically and received radiation therapy ( RT ) as well , 4,500 rads whole brain plus 1,500 rads to the side of the tumor . The median survival time of group A was 30 weeks , while that of group B was 44.5 weeks , but the overall survival curves were not significantly different . The median survival times exceeded the 17 weeks reported elsewhere in comparable patients not receiving postoperative therapy . Estimates of the quality of survival suggested ( 1 ) the two groups were not comparable following r and omization , possibly influencing the results ; and ( 2 ) postoperative radiation and chemotherapy do not increase morbidity and offer a longer period than other treatments during which patients ' conditions remain stable or improve Within three weeks of definitive surgical intervention , 467 patients with histologically proved malignant glioma were r and omized to receive one of four treatment regimens : semustine ( MeCCNU ) , radiotherapy , carmustine ( BCNU ) plus radiotherapy , or semustine plus radiotherapy . We analyzed the data for the total r and omized population and for the 358 patients in whom the initial protocol specifications were met ( the valid study group ) . Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy . Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone . The group receiving carmustine plus radiotherapy had the best survival , but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant . The combination of carmustine plus radiotherapy produced a modest benefit in long-term ( 18-month ) survival as compared with radiotherapy alone , although the difference between survival curves was not significiant at the 0.05 level . This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy |
12,802 | 25,648,806 | Service number and presynchronization did not influence the effect of progesterone supplementation on fertility .
In summary , progesterone supplementation using a single intravaginal insert during the timed AI program increased P/AI mostly in cows without CL and reduced the risk of pregnancy loss in lactating dairy cows .
Insemination of cows in estrus during the synchronization protocol eliminated the benefit of supplemental progesterone on P/AI | A systematic review of the literature was performed with the objective to evaluate the effects of progesterone supplementation using a single intravaginal insert during timed artificial insemination ( AI ) programs on fertility in lactating dairy cows . | Two experiments examined pregnancy after synchronized ovulation ( Ovsynch ) with or without progesterone ( P4 ) administered via controlled internal drug release ( CIDR ) intravaginal inserts . In experiment 1 , 262 lactating cows in one herd were in 3 treatments : Ovsynch ( n = 91 ) , Ovsynch + CIDR ( n = 91 ) , and control ( n = 80 ) . The Ovsynch protocol included injections of GnRH 7 d before and 48 h after an injection of PGF20 . Timed artificial insemination ( TAI ; 57 to 77 d postpartum ) was 16 to 20 h after the second GnRH injection . Cows in the Ovsynch + CIDR group also received a CIDR ( 1.9 g of P4 ) insert for 7 d starting at first GnRH injection . Control cows received A-I when estrus was detected using an electronic estrus detection system . Based on serum P4 , 44.1 % of cows were cyclic before Ovsynch . Pregnancy rates at 29 d ( 59.3 vs. 36.3 % ) and 57 d ( 45.1 vs. 19.8 % ) after TAI and embryo survival ( 75.9 vs. 54.5 % ) from 29 to 57 d were greater for Ovsynch + CIDR than for Ovsynch alone . In experiment 2 , 630 cows in 2 herds received TAI at 59 to 79 d postpartum after 6 treatments . Estrous cycles were either presynchronized ( 2 injections of PGF2alpha 14 d apart ; n = 318 ) or not presynchronized ( n = 312 ) . Within those groups , Ovsynch was initiated 12 d after second presynchronization PGF2alpha , and used alone ( n = 318 ) or with CIDR inserts for 7 d ( 1.38 g of P4/insert , n = 124 or 1.9 g of P4/insert , n = 188 ) . Before Ovsynch , 80 % of cows were cyclic . Presynchronization increased pregnancy ( 46.8 vs. 37.5 % ) at 29 d after TAI , but CIDR inserts had no effect on pregnancy in experiment 2 . Overall embryonic survival between 29 and 57 d in experiment 2 was 57.7 % . Use of CIDR inserts with Ovsynch improved conception and embryo survival in experiment 1 but not in experiment 2 , in part due to differing proportions of cyclic cows at the outset . Presynchronization before Ovsynch enhanced pregnancy rate The objective was to determine the effect of exogenous progesterone ( P4 ) in a timed artificial insemination ( TAI ) protocol initiated at 2 different times post-AI on pregnancies per AI ( P/AI ) in lactating dairy cows . Cows ( n=1,982 ) in 5 dairy herds were assigned r and omly at a nonpregnancy diagnosis 32 ± 3 d post-AI to 1 of 4 resynchronization ( RES ) treatments arranged in a 2 × 2 factorial design using the Ovsynch-56 ( GnRH , 7d later PGF2α , 56 h later GnRH , 16 h later TAI ) protocol . Treatments were as follows : cows initiating RES 32 ± 3 d after AI with no supplemental P4 ( d 32 RES-CON ; n=516 ) ; same as d 32 RES-CON plus a controlled internal drug release ( CIDR ) insert containing P4 at the onset of Ovsynch-56 ( d 32 RES-CIDR ; n=503 ) ; cows initiating RES 39 ± 3 d after AI ( d 39 RES-CON ; n=494 ) ; and same as d 39 RES-CON plus a CIDR ( d 39 RES-CIDR ; n=491 ) . Cows were inseminated if observed in estrus before TAI . The P/AI was determined 32 and 60 d after TAI . In a subgroup of cows ( n=1,152 ) , blood sample s were collected and ovarian structures examined by ultrasonography on the days of the first GnRH ( G1 ) and PGF2α of Ovsynch-56 . Percentage of cows with a corpus luteum ( CL ) at G1 was unaffected by timing of treatments , but percentage of cows with a CL at PGF2α was greater for d 32 than for d 39 cows ( 87.9 vs. 79.4 % ) . In addition , percentage of cows with P4 ≥ 1 ng/mL at G1 was unaffected by timing of treatments , but was increased for d 32 compared with d 39 RES cows on the day of the PGF2α of the RES protocol s ( 86.5 vs. 74.3 % ) . Treatment did not affect ovulation to G1 or P/AI 32 d after RES TAI ( d 32 RES-CON=30.1 % , d 32 RES-CIDR=28.8 % , d 39 RES-CON=27.5 % , d 39 RES-CIDR=30.5 % ) . A greater percentage of d 39 RES cows underwent premature luteolysis during the RES protocol compared with d 32 RES cows . An interaction was detected between day of RES initiation and CIDR treatment , in which the CIDR increased P/AI 60 d after TAI for d 39 ( CON=23.7 % vs. CIDR=28.0 % ) , but not for d 32 ( CON=26.9 % and CIDR=24.2 % ) cows . Pregnancy loss was unaffected by treatment . In addition , cows had improved P/AI 60 d after TAI when they received a CIDR and did not have a CL ( CON-CL=28.2 % , CON-No CL=19.2 % , CIDR-CL=27.0 % , and CIDR-No CL=26.5 % ) or had P4 < 1 ng/mL ( CON-High P4=27.8 % , CON-Low P4=15.0 % , CIDR-High P4=25.0 % , and CIDR-Low P4=29.4 % ) at G1 , but not if a CL was present or P4 was ≥ 1 ng/mL at G1 . In conclusion , addition of a CIDR insert to supplement P4 during the RES protocol increased P/AI for cows initiating RES 39 ± 3 d after AI but not 32 ± 3 d after AI This study evaluated a novel presynchronization method , using Ovsynch prior to the Ovsynch-timed AI protocol ( Double-Ovsynch ) compared to Presynch-Ovsynch . Lactating Holstein ( n=337 ) cows , were assigned to two treatment groups : ( 1 ) Presynch ( n=180 ) , two injections of PGF 14 d apart , followed by the Ovsynch-timed AI protocol 12 d later ; ( 2 ) Double-Ovsynch ( n=157 ) , received GnRH , PGF 7 d later , and GnRH 3 d later , followed by the Ovsynch-timed AI protocol 7 d later . All cows received the same Ovsynch-timed AI protocol : GnRH ( G1 ) at 68+/-3 DIM ( mean+/-SEM ) , PGF 7 d later , GnRH ( G2 ) 56h after PGF , and AI 16 to 20h later . Pregnancy was diagnosed 39 - 45 d after timed AI . Double-Ovsynch increased the pregnancies per AI ( P/AI ) compared to Presynch-Ovsynch ( 49.7 % vs 41.7 % , P=0.03 ) . Surprisingly , Double-Ovsynch increased P/AI only in primiparous ( 65.2 % vs 45.2 % ; P=0.02 ) and not multiparous ( 37.5 % vs 39.3 % ) cows . In a subset of 87 cows , ovarian ultrasonography and progesterone ( P4 ) measurements were performed at G1 and 7 d later . Double-Ovsynch decreased the percentage of cows with low P4 ( < 1ng/mL ) at G1 ( 9.4 % vs 33.3 % ) and increased the percentage of cows with high P4 ( > or = 3ng/mL ) at PGF ( 78.1 % vs 52.3 % ) . Thus , presynchronization of cows with Double-Ovsynch increased fertility in primiparous cows compared to a st and ard Presynch protocol , perhaps due to induction of ovulation in non-cycling cows and improved synchronization of cycling cows . Future studies are needed , with a larger number of cows , to further test the hypothesis of higher fertility with Double-Ovsynch , and to eluci date the physiological mechanisms that underlie apparent changes in fertility with this protocol Lactating Holstein cows ( n = 711 ) on a commercial dairy farm in Wisconsin received a hormonal synchronization protocol to initiate first timed artificial insemination ( TAI ) on the following postpartum schedule : two injections of 25 mg PGF2alpha at 32 + /- 3 d and 46 + /- 3 d ( Presynch ) ; 100 microg GnRH at 60 + /- 3 d ; 25 mg PGF2alpha at 67 + /- 3 d ; and 100 microg GnRH + TAI at 69 + /- 3 d ( Ovsynch ) . At first TAI , cows were r and omly assigned to initiate the first GnRH injection of a hormonal protocol for resynchronization of ovulation ( Resynch ; 100 microg GnRH , d 0 , 25 mg PGF2alpha , d 7 , 100 microg GnRH + TAI , d 9 ) at 19 ( D19 ) , 26 ( D26 ) , or 33 d ( D33 ) after first TAI to set up a second TAI service for cows failing to conceive to Ovsynch . Overall pregnancy rate per artificial insemination ( PR/AI ) to Ovsynch assessed 68 d after TAI was 31 % and did not differ among treatment groups . For Resynch , PR/AI was assessed 26 d after TAI for D19 and D26 cows and 33 d after TAI for D33 cows . Overall PR/AI to Resynch was 32 % . However , the PR/AI for D26 ( 34 % ) and D33 ( 38 % ) cows to Resynch was greater than for D19 cows ( 23 % ) . Cows with a CL at the PGF2alpha injection ( D19 cows ) or at the first GnRH injection ( D26 + D33 cows ) of Resynch exhibited greater PR/AI to Resynch compared with cows without a CL . Survival analysis ( failure time ) of cows in the D26 and D33 treatment groups across the first three TAI services did not differ statistically . Although administration of GnRH to pregnant cows 19 d after first TAI service did not appear to induce iatrogenic embryonic loss , initiation of Resynch 19 d after first TAI service result ed in a lower PR/AI compared with initiation of Resynch 26 or 33 d after first TAI service Objectives were to determine the effect of progesterone ( P4 ) concentration on fertility of lactating dairy cows induced to ovulate follicles of the first follicular wave . Lactating dairy cows ( n=989 ) at 38±3d postpartum were balanced by parity and body condition score and r and omly assigned to 3 treatments : first follicular wave ( FFW ) , first follicular wave with exogenous P4 ( FFWP ) , or second follicular wave ( SFW ) . All cows had their estrous cycle presynchronized with 2 injections of prostagl and in ( PG ) F(2α ) given 14 d apart . Cows in the FFW and FFWP treatments started the ovulation synchronization protocol 3 d after the last PGF(2α ) of the presynchronization protocol , whereas SFW cows received a GnRH injection ( 100 μg of gonadorelin diacetate ; Cystorelin , Merial Ltd. , Duluth , GA ) 3 d after the last PGF(2α ) of the presynchronization protocol and started the synchronization protocol 7 d later . The synchronization protocol consisted of GnRH on d -10 , PGF(2α ) on d -3 , and GnRH concurrent with timed artificial insemination ( AI ) on d 0 . Cows in the FFWP treatment received 2 controlled internal drug release inserts containing 1.38 g of P4 from d -8 to -3 . Progesterone concentration was determined on d -10 , -8 , -6 , -3 , and 0 from all cows and at 7 , 14 , and 21 d after AI from a sub sample of cows ( n=170 ) . Cows ( n=715 ) had their ovaries scanned by ultrasound on d -10 , -3 , and 7 d. Pregnancy was diagnosed at 38 and 66 d after AI . Concentration of P4 from study d -8 to -3 was lowest for FFW cows ( 1.4±0.1 ng/mL ) and similar between SFW ( 3.7±0.2 ng/mL ) and FFWP ( 3.7±0.1 ng/mL ) cows . Diameter of the dominant follicle on study d -3 was greater for FFW cows ( 16.5±0.3 mm ) than for SFW cows ( 15.4±0.3 mm ) , but diameter of the dominant follicle of FFWP cows was not different ( 15.9±0.3 mm ) compared with that of SFW and FFW cows . The incidence of multiple ovulation was largest for FFW cows ( SFW=19.5 , FFW=33.6 , FFWP=19.0 % ) , but pregnancy per AI ( P/AI ) at 66 d was smallest for FFW cows ( SFW=38.9 , FFW=22.3 , FFWP=32.0 % ) . Anovular cows in the SFW ( 19.4 vs. 42.8 % ) and FFWP ( 22.1 vs. 37.2 % ) treatments had reduced P/AI compared with cyclic cows , despite having similar or greater P4 concentration from study d -8 to -3 , respectively . Estrus and ovulation synchronization protocol s for lactating dairy cows must result in growth of ovulatory follicle under P4 concentration > 2 ng/mL to ensure high P/AI The objective of this study was to evaluate the effect of the Ovsynch protocol with and without exogenous progesterone on pregnancy rate ( PR ) in cows in which estrous cycles were previously synchronized with 2 doses of PGF(2alpha ) and that were not detected in estrus during the presynchronization period . The study was conducted in Chihuahua , Mexico ( 8,650 Holstein milking cows ; 305-d mature equivalent milk yield = 13,790 kg ) . On d 47 postpartum , estrous cycles in cows were synchronized by using 2 doses of PGF(2alpha ) 14 d apart . Any cow detected in estrus during this presynchronization period was inseminated . Cows not detected in estrus were selected at r and om and assigned to receive progesterone supplementation or to serve as controls . Controls ( n = 594 ) were subjected to the Ovsynch protocol and cows in the progesterone supplemented treatment ( n = 594 ) were subjected to the Ovsynch protocol plus an intravaginal insert containing 1.9 g of progesterone inserted at the time of the first GnRH injection and removed 7 d later . Progesterone-supplemented cows had a greater PR ( 31.2 % ) compared with controls ( 22.7 % ) . Plasma progesterone concentrations at artificial insemination ( AI ) were < 1 ng/mL and did not differ between treatments . At 14 d post-AI , however , more cows that received progesterone supplementation had concentrations of progesterone > 1 ng/mL compared with controls . It was concluded that after a presynchronization period , cows subjected to the Ovsynch program and supplemented with exogenous progesterone had a greater PR and greater concentrations of progesterone after AI than those subjected to the Ovsynch protocol and not supplemented with progesterone The objectives of this study were to determine the effects of incorporating a progesterone intravaginal insert ( CIDR ) between the day of GnRH and PGF2alpha treatments of a timed AI protocol using estradiol cypionate ( ECP ) to synchronize ovulation on display of estrus , ovulation rate , pregnancy rate , and late embryonic loss in lactating cows . Holstein cows , 227 from Site 1 and 458 from Site 2 , were presynchronized with two injections of PGF2alpha on study d 0 and 14 , and subjected to a timed AI protocol ( 100 mixrog of GnRH on study d 28 , 25 mg of PGF2alpha on study d 35 , 1 mg of ECP on study d 36 , and timed AI on study d 38 ) with or without a CIDR insert . Blood was collected on study d 14 and 28 for progesterone measurements to determine cyclicity . Ovaries were scanned on d 35 , 37 , and 42 , and pregnancy diagnosed on d 65 and 79 , which corresponded to 27 and 41 d after AI . Cows receiving a CIDR had similar rates of detected estrus ( 77.2 vs. 73.8 % ) , ovulation ( 85.6 vs. 86.6 % ) , and pregnancy at 27 ( 35.8 vs. 38.8 % ) and 41 d ( 29.3 vs. 32.3 % ) after AI , and late embryonic loss between 27 and 41 d after AI ( 18.3 vs. 16.8 % ) compared with control cows . The CIDR eliminated cows in estrus before the last PGF2alpha injection and decreased ( P < 0.001 ) the proportion of cows bearing a corpus luteum ( CL ) at the last PGF2alpha injection because of less ovulation in response to the GnRH and greater spontaneous CL regression . Cyclic cows had greater ( P = 0.03 ) pregnancy rates than anovulatory cows at 41 d after AI ( 33.8 vs. 20.4 % ) because of decreased ( P = 0.06 ) late embryonic loss ( 16.0 vs. 30.3 % ) . The ovulatory follicle was larger ( P < 0.001 ) in cows in estrus , and a greater proportion of cows with follicles > or = 15 mm displayed estrus ( P < 0.001 ) and ovulated ( P = 0.05 ) compared with cows with follicles < 15 mm . Pregnancy rates were greater ( P < 0.001 ) for cows displaying estrus , which were related to the greater ( P < 0.001 ) ovulation rate and decreased ( P = 0.08 ) late embryonic loss for cows in estrus at AI . Cows that were cyclic and responded to the presynchronization protocol ( high progesterone at GnRH and CL at PGF2alpha ) had the highest pregnancy rates . Incorporation of a CIDR insert into a presynchronized timed AI protocol using ECP to induce estrus and ovulation did not improve pregnancy rates in lactating dairy cows . Improvements in pregnancy rates in cows treated with ECP to induce ovulation in a timed AI protocol are expected when more cows display estrus , thereby increasing ovulation rate The objective was to compare the probability of pregnancy after fixed-time insemination in cows diagnosed as non-pregnant and re-inseminated following the Ovsynch protocol , with or without exogenous progesterone . Cows ( n=415 ) used in this study originated from 25 farms . Upon diagnosis of non-pregnancy between 30 and 60 days after AI , cows were r and omly assigned to receive either a progesterone releasing intravaginal device ( PRID ; n=208 ) or a placebo intravaginal device ( PID ; n=207 ) . All cows received GnRH at enrollment ( Day 0 ) , PGF(2alpha ) concurrent with intravaginal device removal 7 days later , GnRH on Day 9 and fixed-time insemination 16h later ( Day 10 ) . Cows observed in estrus prior to Day 7 , had the device removed and were inseminated . Ovaries were examined by transrectal palpation at the time of enrollment and the prominent structures were assessed and recorded . Body condition score , lameness status , interval from previous insemination , and times bred at enrollment were recorded . At intravaginal device removal , the occurrence and intensity of vaginitis was determined according to the amount of debris on the device . Overall , the intravaginal device retention rate was 91 % . A total of 5.2 % of PID-treated cows and 2.9 % of PRID-treated cows were detected in estrus within the 7 days treatment period . Pregnancy status was diagnosed between 30 and 56 days after insemination and all cows were followed for a minimum of 150 days after enrollment . Approximately 28 % of cows had evidence of mild vaginitis in response to the intravaginal device , whereas 6 % of cows had copious debris associated with the intravaginal device at removal . The probability of pregnancy after fixed-time insemination was 43.8 % versus 34.9 % in PRID-treated versus PID-treated animals . Exogenous progesterone provided through an intravaginal device to non-pregnant cows that had not displayed estrus improved the probability of pregnancy after fixed-time AI Objectives were to evaluate 3 resynchronization protocol s for lactating dairy cows . At 32+/-3 d after pre-enrollment artificial insemination ( AI ; study d -7 ) , 1 wk before pregnancy diagnosis , cows from 2 farms were enrolled and r and omly assigned to 1 of 3 resynchronization protocol s after balancing for parity , days in milk , and number of previous AI . All cows were examined for pregnancy at 39+/-3 d after pre-enrollment AI ( study d 0 ) . Cows enrolled as controls ( n=386 ) diagnosed not pregnant were su bmi tted to a resynchronization protocol ( d 0-GnRH , d 7-PGF2alpha , and d 10-GnRH and AI ) on the same day . Cows enrolled in the GGPG ( GnRH-GnRH-PGF2alpha-GnRH ) treatment ( n=357 ) received a GnRH injection at enrollment ( d -7 ) and if diagnosed not pregnant were su bmi tted to the resynchronization protocol for control cows on d 0 . Cows enrolled in CIDR treatment ( n=316 ) diagnosed not pregnant received the resynchronization protocol described for control cows with addition of a controlled internal drug release ( CIDR ) insert containing progesterone ( P4 ) from d 0 to 7 . In a subgroup of cows , ovaries were scanned and blood was sample d for P4 concentration on d 0 and 7 . After resynchronized AI , cows were diagnosed for pregnancy at 39+/-3 and 67+/-3 d ( California herds ) or 120+/-3 d ( Arizona herds ) . Cows in the GGPG treatment had more corpora lutea than CIDR and control cows on d 0 ( 1.30+/-0.11 , 1.05+/-0.11 , and 1.05+/-0.11 , respectively ) and d 7 ( 1.41+/-0.14 , 0.97+/-0.13 , and 1.03+/-0.14 , respectively ) . A greater percentage of GGPG cows ovulated to GnRH given on d 0 compared with CIDR and control cows ( 48.4 , 29.6 , and 36.6 % , respectively ) , but CIDR and control did not differ . At 39+/-3 d after resynchronized AI , pregnancy per AI ( P/AI ) was increased in GGPG ( 33.6 % ) and CIDR ( 31.3 % ) cows compared with control ( 24.6 % ) cows . At 67 or 120+/-3 d after resynchronized AI , P/AI of GGPG and CIDR cows was increased compared with control cows ( 31.2 , 29.5 , and 22.1 % , respectively ) . Presynchronizing the estrous cycle of lactating dairy cows with a GnRH 7 d before the start of the resynchronization protocol or use of a CIDR insert within the resynchronization protocol result ed in greater P/AI after resynchronized AI compared with control cows The objective was to examine the effects of presynchronization and bovine somatotropin ( bST ) on pregnancy rates to a timed artificial insemination protocol in lactating dairy cows . Lactating Holstein cows ( n = 543 ) were assigned r and omly in a 2 x 3 factorial experiment in which cows received a presynchronization treatment or not , and were treated with bST ( 500 mg ) at 63 + /- 3 , 73 + /- 3 , or 147 + /- 3 d postpartum . The latter group was used as a control . Presynchronization treatment consisted of two injections of PGF2alpha ( 25 mg ) given 14 d apart , with the second injection of PGF2alpha being administered 12 d before initiation of the timed artificial insemination protocol . All cows received GnRH ( 100 microg ) at 63 + /- 3 d postpartum , an injection of PGF2alpha ( 40 mg ) 7 d later , a GnRH injection at 48 h after PGF2alpha and were inseminated 16 to 20 h later . Cows were resynchronized if determined to be nonpregnant at ultrasonography at 32 d after insemination with a GnRH injection ( 100 microg ) , an injection of PGF2alpha ( 40 mg ) 7 d later , and a GnRH injection at 48 h after PGF2alpha and were inseminated 16 to 20 h later . Cows were examined for pregnancy at 32 d and reexamined at 74 d after insemination . No differences in pregnancy rates were observed between cows receiving bST treatment at 63 + /- 3 d postpartum or at 73 + /- 3 d postpartum . An interaction between presynchronization and bST treatment indicated that pregnancy rates were increased for cows treated with bST when cows were presynchronized . When anestrous cows were excluded from the analyses , both an effect of bST and of presynchronization were observed , indicating that bST increased pregnancy rates regardless of presynchronization treatment and that presynchronization also increased pregnancy rates independently of bST treatment . Presynchronization and bST treatment may be used to increase first-service pregnancy rates to a timed artificial insemination protocol Our objective was to determine the effect of exogenous progesterone ( P4 ) during a timed artificial insemination ( TAI ) protocol on pregnancies per AI ( P/AI ) in dairy cows not previously detected in estrus . Lactating cows ( n=3,248 ) from 7 commercial dairy herds were su bmi tted to a presynchronization protocol ( 2 injections of PGF(2alpha ) 14 d apart ; Presynch ) , and cows in estrus after the second PGF(2alpha ) received AI ( EDAI ; n=1,583 ) . Cows not inseminated by 12 to 14 d after the second PGF(2alpha ) injection were su bmi tted to a TAI protocol ( GnRH on d 0 , PGF(2alpha ) on d 7 , and GnRH+TAI 72h after PGF(2alpha ) ) . At onset of the TAI protocol , cows were balanced by parity and days in milk and assigned r and omly to receive no exogenous P4 ( control , n=803 ) or a controlled internal drug release ( CIDR ) insert containing 1.38 g of P4 from d 0 to 7 ( CIDR , n=862 ) . Blood sample s were collected at the second PGF(2alpha ) injection of the Presynch and on the day of the first GnRH injection of the TAI protocol for P4 determination . When P4 in both sample s was < 1 ng/mL , cows were classified as anovular , whereas cows having at least 1 sample > or=1 ng/mL were classified as cyclic . Concentration of P4 at 11 to 14 d after AI was determined in a subgroup of cows ( n=453 ) from 2 herds . Pregnancy was diagnosed at 40+/-5 and 65+/-5 d after AI . Proportion of cows inseminated on estrus after the second PGF(2alpha ) injection of the Presynch protocol differed among herds ( range=26.7 to 59.8 % ) . Overall P/AI for EDAI cows at 40+/-5 and 65+/-5 d were 36.2 and 33.7 % , respectively , and pregnancy loss was 8.8 % . Proportion of cyclic cows at the onset of the TAI protocol differed among herds ( range from 66.5 to 86.3 % ) , but did not differ between treatments ( control=72.4 % , CIDR=74.1 % ) . Treatment affected P/AI at 40+/-5 ( control=33.3 % , CIDR=38.1 % ) and 65+/-5 ( control=30.0 % , CIDR=35.1 % ) d after AI but did not affect pregnancy loss ( 8.6 % ) . Cyclic cows had greater P/AI at 40+/-5 ( 38.2 vs. 29.3 % ) and 65+/-5 d ( 35.1 vs. 26.1 % ) after AI , but cyclic status had no effect on pregnancy loss . Treatment affected P4 concentration after AI , with more CIDR cows having P4 > or=1 ng/mL ( 94.4 vs. 86.9 % ) and P4 > or=3.2 ng/mL ( 81.8 vs. 68.0 % ) at 11 to 14 d after AI compared with control cows . Treatment of cows not previously detected in estrus with a CIDR insert during a TAI protocol increased proportion of cows with functional CL after AI and P/AI The objectives were to evaluate the effect of supplemental progesterone during a timed artificial insemination ( TAI ) protocol on pregnancy per insemination and pregnancy loss . Lactating dairy cows from 2 dairy herds were presynchronized with 2 injections of PGF(2alpha ) 14 d apart , and cows observed in estrus following the second PGF(2alpha ) injection were inseminated ( n = 1,301 ) . Cows not inseminated by 11 d after the end of the presynchronization were su bmi tted to the TAI protocol ( d 0 GnRH , d 7 PGF(2alpha ) , d 8 estradiol cypionate , and d 10 TAI ) . On the day of the GnRH of the TAI protocol ( study d 0 ) , cows were assigned r and omly to receive no exogenous progesterone ( control = 432 ) , one controlled internal drug-release ( CIDR ) insert ( CIDR1 = 440 ) , or 2 CIDR inserts ( CIDR2 = 440 ) containing 1.38 g of progesterone each from study d 0 to 7 . Blood was sample d on study d 0 before insertion of CIDR for determination of progesterone concentration in plasma , and cows with concentration < 1.0 ng/mL were classified as low progesterone ( LP ) and those with concentration > or = 1.0 ng/mL were classified as high progesterone ( HP ) . From a subgroup of 240 cows , blood was sample d on study d 3 , 7 , 17 and 24 and ovaries were examined by ultrasonography on study d 0 and 7 . Pregnancy was diagnosed at 38 + /- 3 and 66 + /- 3 d after AI . Data were analyzed including only cows r and omly assigned to treatments and excluding cows that were inseminated after the second PGF(2alpha ) injection . The proportion of cows classified as HP at the beginning of the TAI protocol was similar among treatments , but differed between herds . Concentrations of progesterone in plasma during the TAI protocol increased linearly with number of CIDR used , and the increment was 0.9 ng/mL per CIDR . The proportion of cows with plasma progesterone > or = 1.0 ng/mL on study d 17 was not affected by treatment , but a greater proportion of control than CIDR-treated cows had asynchronous estrous cycles following the TAI protocol . Treatment with CIDR inserts , however , did not affect pregnancy at 38 + /- 3 and 66 + /- 3 d after AI or pregnancy loss Cows anestrous at the start of a seasonal breeding period have lesser probability of breeding , lesser conception rates , and a longer interval to conception than cycling herdmates . Historically , treatment included estradiol benzoate , which is no longer available . Consequently , alternative programs are required . Hence , a study was undertaken to assess new treatment regimens for these cows . The presence or absence of a corpus luteum was determined using ultrasonography in cows ( n=2,222 from 12 herds ) that were not detected in estrus by 9 d before the start of breeding . Cows were then r and omly assigned to one of 4 treatments within each herd . Treatments were ( 1 ) 100 microg of gonadorelin , followed 7 d later by 500 microg of sodium cloprostenol , followed 54 to 56h later by 100 microg of gonadorelin , followed by fixed-time artificial insemination at 13 to 18h after the final GnRH injection ( Ovsynch ) ; ( 2 ) as for ( 1 ) but with placement of an intravaginal progesterone (P4)-releasing insert between the initial GnRH and PGF(2alpha ) ( Ovsynch-56+P4 ) ; ( 3 ) as for ( 2 ) but with the final GnRH treatment delayed until 71h after PGF(2alpha ) and P4 insert removal with fixed-time artificial insemination 0 to 5h after GnRH treatment and with insemination of those cows detected in estrus before the second GnRH injection ( Cosynch-72+P4 ) ; and ( 4 ) untreated controls ( control ) . Day 0 was defined as the day of the second GnRH injection . Milk sample s were collected from 154 and 152 cows from the Ovsynch and Ovsynch-56+P4 treatments , respectively , at d 0 , 7 , and 14 for P4 concentration determination . This was to test the hypothesis that inclusion of P4 would result in a greater proportion of cows having normal luteal function after treatment in these 2 groups that differed only in the inclusion of P4 in the Ovsynch-56+P4 treatment . All treatments result ed in shorter intervals from first day of breeding to conception compared with the controls . The Ovsynch-56+P4 treatment result ed in start of breeding to conception intervals 3 , 6 , and 16 d shorter than those of Cosynch-72+P4 , Ovsynch , or controls , respectively , and the positive effect of the Ovsynch-56+P4 treatment occurred both in corpus-luteum-positive and in corpus-luteum-negative cows . The Ovsynch-56+P4 treatment result ed in fewer short interestrus intervals than did Ovsynch ( i.e. , < 18 d ; 16 vs. 31 % ) and more cows with elevated ( > 1 ng/mL ) milk P4 concentrations at d 7 ( 88 vs. 74 % ) and d 14 ( 80 vs. 60 % ) . It was concluded that treatment of anestrous cows before the start of breeding result ed in earlier conception than no treatment but had no effect on the final pregnancy rate . The addition of P4 to the Ovsynch program result ed in earlier conception and in more cows with normal subsequent luteal-phase lengths Objectives were to evaluate progesterone concentrations after cows had initiated estrous cycles following calving and induction of estrous cycles in postpartum anovular high-producing Holstein dairy cows treated with controlled internal drug releasing ( CIDR ) . In experiment 1 ( EXP1 ) , 62 cows that had initiated estrous cycles received a new CIDR ( NCIDR ) containing 1.38 g of progesterone or a 7-d used autoclaved CIDR ( UCIDR ) 48h after luteolysis for 7 d. Ovaries were examined by ultrasonography , and plasma analyzed for concentrations of progesterone . In experiment 2 ( EXP2 ) , 515 cows diagnosed as anestrus were r and omly assigned to untreated control , NCIDR or UCIDR for 6d . Plasma was analyzed for concentration of progesterone 12 d after CIDR removal to determine ovulation . In EXP1 , milk yield and body condition did not influence progesterone concentrations . Concentration of progesterone tended to increase faster ( P=0.10 ) in cows receiving UCIDR than NCIDR , but both treatments reached a plateau at 90min . Cows receiving the NCIDR had greater ( P=0.04 ) concentrations of progesterone during the 7-d treatment , but they were mostly subluteal ( < 1.0 ng/mL ) after d 2 . After removal , concentrations of progesterone were greater for NCIDR than UCIDR for the first 45 min , and were similar thereafter . Multiparous cows had lesser ( P=0.004 ) concentrations than primiparous cows throughout the study . The pattern of ovarian follicular development was not affected by treatment . In EXP2 , induction of onset of estrous cycles increased ( P<0.01 ) with progesterone treatments , but was similar between NCIDR and UCIDR . Proportion of cows experiencing shorter than typical length estrous cycles after first AI tended to be greater ( P=0.09 ) for control cows than those receiving the CIDR , and for cows remaining anestrous than those in which onset of estrous cycles was induced . Pregnancy per AI and pregnancy loss were similar among treatments . Cows that resumed estrous cyclicity prior to first AI had greater ( P=0.01 ) pregnancy per AI . Treatment of high-producing Holstein cows that had previously initiated onset of estrous cycles with CIDR result ed in subluteal concentrations of progesterone , but in anestrous high-producing cows increased induction of estrous cycles with no effect on fertility at first insemination The objectives were to evaluate pregnancy per AI ( P/AI ) of dairy cows subjected to the 5-day timed AI protocol under various synchronization and luteolytic treatments . Cows were either presynchronized or received supplemental progesterone during the synchronization protocol , and received a double luteolytic dose of PGF2α , either as one or two injections . In Experiment 1 , dairy cows ( n=737 ; Holstein=250 , Jersey=80 , and crossbred=407 ) in two seasonal grazing dairy farms were r and omly assigned to one of four treatments in a 2 × 2 factorial arrangement . The day of AI was considered study Day 0 . Half of the cows were presynchronized ( G6 G : PGF2α on Day -16 and GnRH on Day -14 ) and received the 5-day timed AI protocol using 1 mg of cloprostenol , either as a single injection ( G6G-S : GnRH on Day -8 , PGF2α on Day -3 , and GnRH+AI on Day 0 ) or divided into two injections of 0.5 mg each ( G6G-T : GnRH on Day -8 , PGF2α on Day -3 and -2 , and GnRH+AI on Day 0 ) . The remaining cows were not presynchronized and received a controlled internal drug-release ( CIDR ) insert containing progesterone from GnRH to the first PGF2α injection of the 5-day timed AI protocol , and 1 mg of cloprostenol either as a single injection on Day -3 ( CIDR-S ) or divided into two injections of 0.5 mg each on Days -3 and -2 ( CIDR-T ) . Ovaries were examined by ultrasonography on Days -8 and -3 and plasma progesterone concentrations were determined on Days -3 and 0 . In Experiment 2 , 655 high-producing Holstein cows had their estrous cycle presynchronized with PGF2α at 46±3 and 60±3 days postpartum and were r and omly assigned to receive 50 mg of dinoprost during the 5-day timed AI protocol , either as a single injection or divided into two injections of 25 mg each . Pregnancies per AI were determined on Days 35 and 64 after AI in both experiments . In Experiment 1 , presynchronization with G6 G increased the proportion of cows with a CL on Day -8 ( 80.6 vs. 58.8 % ) , ovulation to the first GnRH of the protocol ( 64.2 vs. 50.2 % ) , and the presence ( 95.6 vs. 88.4 % ) and number ( 1.79 vs. 1.30 ) of CL at PGF(2α ) compared with CIDR cows . Luteolysis was greater for two injections compared to a single PGF2α injection ( two PGF2α=95.9 vs. single PGF2α=72.2 % ) , especially in presynchronized cows ( G6G-T=96.2 vs. G6G-S=61.7 % ) . For cows not presynchronized , two PGF2α injections had no effect on P/AI ( CIDR-S=30.2 vs. CIDR-T=34.3 % ) , whereas for presynchronized cows , it improved P/AI ( G6G-S=28.7 vs. G6G-T=45.4 % ) . In Experiment 2 , the two-PGF2α injection increased P/AI on Days 35 ( two PGF2α=44.5 vs. single PGF2α=36.4 % ) and 64 ( two PGF2α=40.3 % vs. single PGF2α=32.6 % ) after AI . Presynchronization and dividing the dose of PGF2α ( either cloprostenol or dinoprost ) into two injections increased P/AI in lactating dairy cows subjected to the 5-day timed AI protocol Our objective was to determine whether progesterone ( P4 ) supplementation during an Ovsynch protocol would enhance fertility in lactating dairy cows . Lactating dairy cows ( n = 634 ) at 6 locations were assigned r and omly within lactation number and stage of lactation to receive the Ovsynch protocol [ OVS ; synchronization of ovulation by injecting GnRH 7 d before and 48 h after PGF(2alpha ) , followed by one fixed-time AI ( TAI ) 16 to 20 h after the second GnRH injection ] or Ovsynch plus a controlled internal drug release ( CIDR ) P4-releasing insert for 7 d , beginning at the first GnRH injection ( OVS + CIDR ) . Blood was sample d to quantify P4 10 d before the first GnRH injection , immediately before the first GnRH injection , at the time of CIDR removal , before the PGF(2alpha ) injection ( 1 to 2 h after CIDR insert removal ) , and 48 h after the PGF(2alpha ) injection to determine cyclicity status before initiation of treatment , luteal status at the PGF(2alpha ) injection , and incidence of luteal regression . Overall , conception rates at 28 ( 40 vs. 50 % ) and 56 d ( 33 vs. 38 % ) after TAI differed between OVS and OVS + CIDR , respectively ; but a treatment x location interaction was detected . Compared with OVS , pregnancy outcomes were more positive for OVS + CIDR cows at 4 of 6 locations 28 d after TAI and at 3 of 6 locations 56 d after TAI . An interaction of luteal status ( high vs. low ) before CIDR insert removal and PGF(2alpha ) injection with pretreatment cycling status indicated that cows having low P4 at PGF(2alpha ) injection benefited most from P4 supplementation ( OVS + CIDR = 36 % vs. OVS = 18 % ) , regardless of pretreatment cycling status . Pregnancy loss between 28 and 56 d after TAI was greater for noncycling cows ( 31 % ) compared with cycling cows ( 16 % ) . Pregnancy loss for cows receiving P4 ( 21 % ) did not differ from that for cows not receiving P4 ( 21 % ) . Supplementation of P4 , pretreatment cycling status , and luteal status before PGF(2alpha ) injection altered follicular diameters at the time of the second GnRH injection , but were unrelated to pregnancy outcomes . Incidence of multiple ovulation was greater in noncycling than in cycling cows . Further , cows having multiple ovulations had improved pregnancy outcomes at 28 and 56 d after TAI . In summary , a CIDR insert during the Ovsynch protocol increased fertility in lactating cows having low serum P4 before PGF(2alpha ) injection . Improved pregnancy outcomes were observed at some , but not all locations The objectives of this study were to evaluate the effects of an intravaginal insert containing progesterone ( CIDR , controlled internal drug releasing ) administered in presynchronization and resynchronization protocol s on cyclicity , detection of estrus , pregnancy rate , and pregnancy loss to first AI ; reinsemination patterns ; and pregnancy rates to second postpartum AI before and after the time of first-service pregnancy diagnosis in dairy cows . Holstein cows ( n = 1,052 ) were blocked by parity and BCS at 3 + /- 3 d in milk ( study d 0 = day of calving ) and assigned r and omly to 1 of 3 presynchronization treatments . During the presynchronization programs , all cows received 2 injections of PGF2alpha , on study d 35 and 49 . Cows enrolled in the control presynchronization treatment received AI after detected estrus from study d 49 to 62 . Cows enrolled in the CIDR estrus-detection ( CED ) presynchronization treatment received a CIDR insert from study d 42 to 49 and AI on detection of estrus from d 49 to 62 . Cows enrolled in the CIDR timed AI ( CTAI ) presynchronization treatment received the same treatment as CED , but were subjected to timed AI on study d 72 after the Ovsynch ( GnRH , 7 d PGF2alpha , 2 d GnRH , 24 h timed AI ) protocol . The control and CED cows not inseminated by study d 62 were enrolled in the Ovsynch protocol on the same day and received timed AI on study d 72 . After first AI , cows were assigned to no resynchronization ( RCON ) or resynchronization with a CIDR insert ( RCIDR ) between 14 and 21 d after AI . Blood sample s collected on study d 35 , 49 , and 62 were analyzed for concentrations of progesterone and cows were classified as anestrous when progesterone was < 1.0 ng/mL in the first 2 sample s. On study d 62 , anestrous cows with progesterone > or = 1.0 ng/mL were classified as having resumed cyclicity . Pregnancy was diagnosed at 31 and 60 d after first AI and at 42 d after second AI . A greater proportion of anestrous cows in CED and CTAI became cyclic by d 62 postpartum than control cows . Resynchronization with the CIDR insert increased the pregnancy rate at 31 d after first AI in CED and CTAI , and at 60 d after AI in all cows because of reduced pregnancy loss . These results indicate that presynchronization with the CIDR insert increased induction of cyclicity in anestrous cows and that resynchronization with the CIDR insert did not affect the reinsemination rate but did reduce pregnancy loss and increased the pregnancy rate at 60 d after first AI Lactating dairy cows ( n=1,538 ) were enrolled in a r and omized complete block design study to evaluate protocol s to synchronize estrus and ovulation . Within each herd ( n=8 ) , cows were divided into 3 calving groups : early , mid , and late , based on days in milk ( DIM ) at mating start date ( MSD ) . Early calving cows ( n=1,244 ) were ≥42 DIM at MSD , mid-calving cows ( n=179 ) were 21 to 41 DIM at MSD , and late-calving cows ( n=115 ) were 0 to 20 DIM at MSD . Cows in the early , mid- , and late-calving groups were synchronized to facilitate estrus or timed AI ( TAI ) at MSD ( planned breeding 1 ; PB1 ) , 21 d ( PB2 ) , and 42 d ( PB3 ) after MSD , respectively . For each PB , cows in the relevant calving group were stratified by parity and calving date and r and omly assigned to 1 of 4 experimental groups : ( 1 ) d -10 GnRH ( 10 μg of i.m . buserelin ) and controlled internal drug release insert ( CIDR ; 1.38 g of progesterone ) ; d -3 PGF(2α ) ( 25 mg of i.m . dinoprost ) ; and d -2 CIDR out and AI at observed estrus ( CIDR_OBS ) ; ( 2 ) same as CIDR_OBS , but GnRH 36 h after CIDR out and TAI 18 h later ( CIDR_TAI ) ; ( 3 ) same as CIDR_TAI , but no CIDR ( Ovsynch ) ; or ( 4 ) untreated controls ( CTRL ) . The CIDR_OBS , CIDR_TAI , and Ovsynch had shorter mean intervals from calving to first service compared with the CTRL ( 69.2 , 63.4 , and 63.7 vs. 73.7 d , respectively ) . Both CIDR_OBS ( predicted probability ; PP of pregnancy=0.59 ) and CIDR_TAI ( PP of pregnancy=0.54 ) had increased odds of conceiving at first service compared with Ovsynch [ PP of pregnancy=0.45 ; odds ratio (OR)=1.81 and OR=1.46 , respectively ] , and Ovsynch had decreased likelihood of conceiving at first service ( OR=0.70 ) compared with CTRL ( PP of pregnancy=0.53 ) . Both CIDR_TAI hazard ratio ; HR [ 95 % confidence interval=1.21 ( 1.04 , 1.41 ) ] and Ovsynch [ HR ( 95 % confidence interval)=1.23 ( 1.05 , 1.44 ) ] were associated with an increased likelihood of earlier conception compared with the CTRL . A greater proportion of cows on the CIDR_TAI treatment successfully established pregnancy in the first 42 d of the breeding season compared with the CTRL ( 0.75 vs. 0.67 PP of 42-d pregnancy , respectively ) . Protocol s to synchronize estrus and ovulation were effective at achieving earlier first service and conception in pasture-based seasonal calving dairy herds . However , animals that conceived following insemination at observed estrus had a decreased likelihood of embryo loss to first service compared with animals bred with TAI ( PP of embryo loss after first service=0.05 vs. 0.09 ; OR=0.52 ) Objectives were to evaluate the effects of differing progesterone concentrations during follicle development on follicular dynamics , fertilization , and embryo quality . Lactating Holstein cows ( n=154 ) were assigned r and omly to 1 of 2 treatments . Cows underwent a presynchronization of the estrous cycle composed of an injection of GnRH concurrently with the placement of a progesterone insert , an injection of PGF(2α ) and insert removal 7 d later , and a second injection of GnRH 48 h later ( study d -16 ) . All cows were then su bmi tted to a hormonal protocol identical to the presynchronization program starting on d 7 of the estrous cycle ( study d -9 ) . Cows enrolled in the high progesterone ( HP ) treatment received no further treatment . Cows in the low progesterone ( LP ) treatment received additional PGF(2α ) injections on study d -14 , -13.5 , and -13 and again on study d -9 , -7 , -6.5 , and -6 . Ovaries were evaluated by ultrasonography , and blood was sample d for concentrations of progesterone and estradiol throughout the study . Uteri were flushed 6 d after artificial insemination ( AI ) and recovered oocytes-embryos were evaluated . Concentrations of progesterone were less for LP cows from study d -7 to -2 ; concentrations of estradiol at PGF(2α ) and at the last GnRH of synchronization were greater for LP than HP . The proportion of cows in estrus at AI was greater for LP than for HP ( 38.0 vs. 5.3 % ) . Ovulatory follicles of LP cows had larger diameters at the injections of PGF(2α ) ( 17.2 vs. 14.6 mm ) and final GnRH ( 19.4 vs. 16.9 % ) of the synchronization , which result ed in a larger diameter of the corpus luteum 6 d after AI ( 24.3 vs. 22.6 mm ) . Double ovulation after the last GnRH of the synchronization was increased in LP ( 18.6 % ) compared with HP ( 4.5 % ) . Fertilization rate was similar and averaged 82.7 % . The proportion of embryos and oocytes-embryos classified as grade s 1 and 2 , proportion of degenerated embryos , and unfertilized-degenerated oocytes-embryos were not different between LP and HP . Number of blastomeres did not differ between LP and HP , but the proportion of live blastomeres tended to be less for LP than HP ( 94.2 vs. 98.7 % ) . Reducing progesterone concentrations during the synchronization program altered concentrations of estradiol and follicular dynamics , but result ed in similar fertilization and only minor changes in embryo quality The objective was to determine if reducing the interval from presynchronization to the first GnRH injection ( G1 ) of a timed artificial insemination ( AI ) protocol improves pregnancy per AI . One thous and two hundred fourteen Holstein cows , at 37 + /- 3 d in milk ( DIM ) , were stratified by parity , DIM , and milk yield in the first month postpartum and r and omly assigned to control ( n = 412 ) , 2 injections of PGF2alpha at 37 + /- 3 and 51 + /- 3 DIM , then enrolled in a timed AI protocol 14 d later ; PShort ( n = 410 ) , 2 injections of PGF2alpha at 40 + /- 3 and 54 + /- 3 DIM , then enrolled in a timed AI protocol 11 d later ; or PShortG ( n = 392 ) , same as PShort , but with an injection of GnRH 7 d before G1 . All cows received the same timed AI protocol ( d 65 , G1 ; d 72 , PGF2alpha ; d 73 , 1 mg of estradiol cypionate ; d 75 , AI ) . A subset of 1,000 cows had their ovaries examined by ultrasonography at G1 and 7 d later when PGF2alpha of the timed AI was given to determine presence of corpus luteum ( CL ) and ovulation to G1 . Pregnancy was diagnosed on d 38 after timed AI , and pregnant cows were reevaluated for pregnancy 4 wk later . Altering the interval between presynchronization and G1 did not affect the proportion of cows with a CL at G1 , but GnRH 7 d before G1 increased the proportion of cows with a CL . Ovulation to G1 was greater for 11 compared with the 14 d interval , but GnRH did not improve ovulation . The increased ovulation to G1 when the interval was reduced from 14 to 11 d was observed only in cows with a CL at G1 , but treatment did not affect ovulation in cows without a CL at G1 . Treatment affected the pregnancy per AI on d 38 and 66 after insemination , and they were greater for the 11 compared with 14-d interval , but addition of GnRH did not improve pregnancy per AI . Cows ovulating to G1 had greater pregnancy per AI regardless of whether or not they had a CL at G1 . Reducing the interval from presynchronization to initiation of the timed AI protocol from 14 to 11 d increased ovulation to G1 and pregnancy per AI in lactating dairy cows The objectives of this study were to determine the effects of supplemental progesterone on fertility responses of lactating dairy cows with a CL at the initiation of the timed artificial insemination ( AI ) program . Holstein cows were subjected to the Ovsynch protocol ( Day -10 GnRH , Day -3 PGF2α , Day -0.7 GnRH , and Day 0 timed AI ) . Ovaries were scanned by ultrasonography on Day -10 and cows with CL were blocked by pen and assigned r and omly to receive no supplemental progesterone ( control , n = 863 ) or to receive a controlled internal drug-release ( CIDR ) insert containing progesterone from Days -10 to -3 ( 1CIDR , n = 862 ) . Cows were observed for signs of estrus beginning on Day -9 based on removal of tail chalk and those in estrus received AI on the same day . Blood sample d from a subset of cows was analyzed for progesterone concentrations on Days -10 , -9 , -7 , -5 , -3 , 0 , 6 , 13 , and 19 . Pregnancy was diagnosed on Days 32 and 60 after AI . Supplementation increased ( P < 0.01 ) progesterone concentrations between Day -9 and -3 compared with control ( 7.5 vs. 6.2 ng/mL ) . Treatment had no effect on the ovulatory response to the first and final GnRH injections of the Ovsynch protocol , the proportion of cows that maintained their CL until the day of PGF2α injection , or the diameter of the ovulatory follicle before AI . Although the overall proportion of cows in estrus at AI did not differ between treatments , progesterone supplementation prevented ( P < 0.01 ) cows from coming into estrus from Days -9 to -3 ( 0.0 % vs. 4.7 % ) , whereas it increased ( P = 0.02 ) the proportion of cows inseminated in estrus from Days -2 to -1 ( 7.1 % vs. 4.5 % ) . Pregnancy per AI ( P/AI ) tended to be reduced ( P = 0.06 ) by supplemental progesterone on Day 32 ( 40.5 % vs. 45.0 % ) , but not on Day 60 after AI ( 36.6 % vs. 39.7 % ) . A tendency for an interaction ( P = 0.09 ) between treatment and the presence of CL at the PGF2α injection was observed for P/AI on Day 32 in cows that received timed AI because progesterone supplementation reduced P/AI in cows that maintained their CL until Day -3 ( 40.3 % vs. 46.7 % ) ; however , it increased P/AI in those that did not have a CL at PGF2α ( 38.1 % vs. 27.7 % ) . Treatment did not affect pregnancy loss between Days 32 and 60 of gestation . In conclusion , incorporating a single intravaginal insert to the timed AI program increased progesterone concentrations in plasma by 1.3 ng/mL , but did not benefit fertility in dairy cows that have CL at the initiation of the synchronization protocol |
12,803 | 30,425,525 | Data suggested that PD-1 inhibitors had higher efficacy and safety profiles than PD-L1 and CTLA-4 inhibitors in combination ICI therapy for lung cancer patients .
However , the current data do not support the large-scale clinical application of combination ICI therapy in SCLC patients | The value of immune checkpoint inhibitor ( ICI ) combination therapy for patients with lung cancer remains unclear . | BACKGROUND Treatments for small-cell lung cancer ( SCLC ) after failure of platinum-based chemotherapy are limited . We assessed safety and activity of nivolumab and nivolumab plus ipilimumab in patients with SCLC who progressed after one or more previous regimens . METHODS The SCLC cohort of this phase 1/2 multicentre , multi-arm , open-label trial was conducted at 23 sites ( academic centres and hospitals ) in six countries . Eligible patients were 18 years of age or older , had limited-stage or extensive-stage SCLC , and had disease progression after at least one previous platinum-containing regimen . Patients received nivolumab ( 3 mg/kg bodyweight intravenously ) every 2 weeks ( given until disease progression or unacceptable toxicity ) , or nivolumab plus ipilimumab ( 1 mg/kg plus 1 mg/kg , 1 mg/kg plus 3 mg/kg , or 3 mg/kg plus 1 mg/kg , intravenously ) every 3 weeks for four cycles , followed by nivolumab 3 mg/kg every 2 weeks . Patients were either assigned to nivolumab monotherapy or assessed in a dose-escalating safety phase for the nivolumab/ipilimumab combination beginning at nivolumab 1 mg/kg plus ipilimumab 1 mg/kg . Depending on tolerability , patients were then assigned to nivolumab 1 mg/kg plus ipilimumab 3 mg/kg or nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . The primary endpoint was objective response by investigator assessment . All analyses included patients who were enrolled at least 90 days before data base lock . This trial is ongoing ; here , we report an interim analysis of the SCLC cohort . This study is registered with Clinical Trials.gov , number NCT01928394 . FINDINGS Between Nov 18 , 2013 , and July 28 , 2015 , 216 patients were enrolled and treated ( 98 with nivolumab 3 mg/kg , three with nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 61 with nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 54 with nivolumab 3 mg/kg plus ipilimumab 1 mg/kg ) . At data base lock on Nov 6 , 2015 , median follow-up for patients continuing in the study ( including those who had died or discontinued treatment ) was 198·5 days ( IQR 163·0 - 464·0 ) for nivolumab 3 mg/kg , 302 days ( IQR not calculable ) for nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 361·0 days ( 273·0 - 470·0 ) for nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and 260·5 days ( 248·0 - 288·0 ) for nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . An objective response was achieved in ten ( 10 % ) of 98 patients receiving nivolumab 3 mg/kg , one ( 33 % ) of three patients receiving nivolumab 1 mg/kg plus ipilimumab 1 mg/kg , 14 ( 23 % ) of 61 receiving nivolumab 1 mg/kg plus ipilimumab 3 mg/kg , and ten ( 19 % ) of 54 receiving nivolumab 3 mg/kg plus ipilimumab 1 mg/kg . Grade 3 or 4 treatment-related adverse events occurred in 13 ( 13 % ) patients in the nivolumab 3 mg/kg cohort , 18 ( 30 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg cohort , and ten ( 19 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( none vs 5 [ 8 % ] vs none ) and diarrhoea ( none vs 3 [ 5 % ] vs 1 [ 2 % ] ) . No patients in the nivolumab 1 mg/kg plus ipilimumab 1 mg/kg cohort had a grade 3 or 4 treatment-related adverse event . Six ( 6 % ) patients in the nivolumab 3 mg/kg group , seven ( 11 % ) in the nivolumab 1 mg/kg plus ipilimumab 3 mg/kg group , and four ( 7 % ) in the nivolumab 3 mg/kg plus ipilimumab 1 mg/kg group discontinued treatment due to treatment-related adverse events . Two patients who received nivolumab 1 mg/kg plus ipilimumab 3 mg/kg died from treatment-related adverse events ( myasthenia gravis and worsening of renal failure ) , and one patient who received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg died from treatment-related pneumonitis . INTERPRETATION Nivolumab monotherapy and nivolumab plus ipilimumab showed antitumour activity with durable responses and manageable safety profiles in previously treated patients with SCLC . These data suggest a potential new treatment approach for a population of patients with limited treatment options and support the evaluation of nivolumab and nivolumab plus ipilimumab in phase 3 r and omised controlled trials in SCLC . FUNDING Bristol-Myers Squibb BACKGROUND Limited evidence exists to show that adding a third agent to platinum-doublet chemotherapy improves efficacy in the first-line advanced non-small-cell lung cancer ( NSCLC ) setting . The anti-PD-1 antibody pembrolizumab has shown efficacy as monotherapy in patients with advanced NSCLC and has a non-overlapping toxicity profile with chemotherapy . We assessed whether the addition of pembrolizumab to platinum-doublet chemotherapy improves efficacy in patients with advanced non-squamous NSCLC . METHODS In this r and omised , open-label , phase 2 cohort of a multicohort study ( KEYNOTE-021 ) , patients were enrolled at 26 medical centres in the USA and Taiwan . Patients with chemotherapy-naive , stage IIIB or IV , non-squamous NSCLC without targetable EGFR or ALK genetic aberrations were r and omly assigned ( 1:1 ) in blocks of four stratified by PD-L1 tumour proportion score ( < 1 % vs ≥1 % ) using an interactive voice-response system to 4 cycles of pembrolizumab 200 mg plus carboplatin area under curve 5 mg/mL per min and pemetrexed 500 mg/m2 every 3 weeks followed by pembrolizumab for 24 months and indefinite pemetrexed maintenance therapy or to 4 cycles of carboplatin and pemetrexed alone followed by indefinite pemetrexed maintenance therapy . The primary endpoint was the proportion of patients who achieved an objective response , defined as the percentage of patients with radiologically confirmed complete or partial response according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by masked , independent central review , in the intention-to-treat population , defined as all patients who were allocated to study treatment . Significance threshold was p<0·025 ( one sided ) . Safety was assessed in the as-treated population , defined as all patients who received at least one dose of the assigned study treatment . This trial , which is closed for enrolment but continuing for follow-up , is registered with Clinical Trials.gov , number NCT02039674 . FINDINGS Between Nov 25 , 2014 , and Jan 25 , 2016 , 123 patients were enrolled ; 60 were r and omly assigned to the pembrolizumab plus chemotherapy group and 63 to the chemotherapy alone group . 33 ( 55 % ; 95 % CI 42 - 68 ) of 60 patients in the pembrolizumab plus chemotherapy group achieved an objective response compared with 18 ( 29 % ; 18 - 41 ) of 63 patients in the chemotherapy alone group ( estimated treatment difference 26 % [ 95 % CI 9 - 42 % ] ; p=0·0016 ) . The incidence of grade 3 or worse treatment-related adverse events was similar between groups ( 23 [ 39 % ] of 59 patients in the pembrolizumab plus chemotherapy group and 16 [ 26 % ] of 62 in the chemotherapy alone group ) . The most common grade 3 or worse treatment-related adverse events in the pembrolizumab plus chemotherapy group were anaemia ( seven [ 12 % ] of 59 ) and decreased neutrophil count ( three [ 5 % ] ) ; an additional six events each occurred in two ( 3 % ) for acute kidney injury , decreased lymphocyte count , fatigue , neutropenia , and sepsis , and thrombocytopenia . In the chemotherapy alone group , the most common grade 3 or worse events were anaemia ( nine [ 15 % ] of 62 ) and decreased neutrophil count , pancytopenia , and thrombocytopenia ( two [ 3 % ] each ) . One ( 2 % ) of 59 patients in the pembrolizumab plus chemotherapy group experienced treatment-related death because of sepsis compared with two ( 3 % ) of 62 patients in the chemotherapy group : one because of sepsis and one because of pancytopenia . INTERPRETATION Combination of pembrolizumab , carboplatin , and pemetrexed could be an effective and tolerable first-line treatment option for patients with advanced non-squamous NSCLC . This finding is being further explored in an ongoing international , r and omised , double-blind , phase 3 study . FUNDING Merck & BACKGROUND Nivolumab plus ipilimumab showed promising efficacy for the treatment of non – small‐cell lung cancer ( NSCLC ) in a phase 1 trial , and tumor mutational burden has emerged as a potential biomarker of benefit . In this part of an open‐label , multipart , phase 3 trial , we examined progression‐free survival with nivolumab plus ipilimumab versus chemotherapy among patients with a high tumor mutational burden ( ≥10 mutations per megabase ) . METHODS We enrolled patients with stage IV or recurrent NSCLC that was not previously treated with chemotherapy . Those with a level of tumor programmed death lig and 1 ( PD‐L1 ) expression of at least 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab monotherapy , or chemotherapy ; those with a tumor PD‐L1 expression level of less than 1 % were r and omly assigned , in a 1:1:1 ratio , to receive nivolumab plus ipilimumab , nivolumab plus chemotherapy , or chemotherapy . Tumor mutational burden was determined by the FoundationOne CDx assay . RESULTS Progression‐free survival among patients with a high tumor mutational burden was significantly longer with nivolumab plus ipilimumab than with chemotherapy . The 1‐year progression‐free survival rate was 42.6 % with nivolumab plus ipilimumab versus 13.2 % with chemotherapy , and the median progression‐free survival was 7.2 months ( 95 % confidence interval [ CI ] , 5.5 to 13.2 ) versus 5.5 months ( 95 % CI , 4.4 to 5.8 ) ( hazard ratio for disease progression or death , 0.58 ; 97.5 % CI , 0.41 to 0.81 ; P<0.001 ) . The objective response rate was 45.3 % with nivolumab plus ipilimumab and 26.9 % with chemotherapy . The benefit of nivolumab plus ipilimumab over chemotherapy was broadly consistent within subgroups , including patients with a PD‐L1 expression level of at least 1 % and those with a level of less than 1 % . The rate of grade 3 or 4 treatment‐related adverse events was 31.2 % with nivolumab plus ipilimumab and 36.1 % with chemotherapy . CONCLUSIONS Progression‐free survival was significantly longer with first‐line nivolumab plus ipilimumab than with chemotherapy among patients with NSCLC and a high tumor mutational burden , irrespective of PD‐L1 expression level . The results vali date the benefit of nivolumab plus ipilimumab in NSCLC and the role of tumor mutational burden as a biomarker for patient selection . ( Funded by Bristol‐Myers Squibb and Ono Pharmaceutical ; CheckMate 227 Clinical Trials.gov number , NCT02477826 . BACKGROUND Nivolumab has shown improved survival in the treatment of advanced non-small-cell lung cancer ( NSCLC ) previously treated with chemotherapy . We assessed the safety and activity of combination nivolumab plus ipilimumab as first-line therapy for NSCLC . METHODS The open-label , phase 1 , multicohort study ( CheckMate 012 ) cohorts reported here were enrolled at eight US academic centres . Eligible patients were aged 18 years or older with histologically or cytologically confirmed recurrent stage IIIb or stage IV , chemotherapy-naive NSCLC . Patients were r and omly assigned ( 1:1:1 ) by an interactive voice response system to receive nivolumab 1 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks , nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 12 weeks , or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks until disease progression , unacceptable toxicities , or withdrawal of consent . Data from the latter two cohorts , which were considered potentially suitable for further clinical development , are presented in this report ; data from the other cohort ( as well as several earlier cohorts ) are described in the appendix . The primary outcome was safety and tolerability , assessed in all treated patients . This ongoing study is registered with Clinical Trials.gov , number NCT01454102 . FINDINGS Between May 15 , 2014 , and March 25 , 2015 , 78 patients were r and omly assigned to receive nivolumab every 2 weeks plus ipilimumab every 12 weeks ( n=38 ) or nivolumab every 2 weeks plus ipilimumab every 6 weeks ( n=40 ) . One patient in the ipilimumab every-6-weeks cohort was excluded before treatment ; therefore 77 patients actually received treatment ( 38 in the ipilimumab every-12-weeks cohort ; 39 in the ipilimumab every-6-weeks cohort ) . At data cut-off on Jan 7 , 2016 , 29 ( 76 % ) patients in the ipilimumab every-12-weeks cohort and 32 ( 82 % ) in the ipilimumab every-6-weeks cohort had discontinued treatment . Grade 3 - 4 treatment-related adverse events occurred in 14 ( 37 % ) patients in the ipilimumab every-12-weeks cohort and 13 ( 33 % ) patients in the every-6-weeks cohort ; the most commonly reported grade 3 or 4 treatment-related adverse events were increased lipase ( three [ 8 % ] and no patients ) , pneumonitis ( two [ 5 % ] and one [ 3 % ] patients ) , adrenal insufficiency ( one [ 3 % ] and two [ 5 % ] patients ) , and colitis ( one [ 3 % ] and two [ 5 % ] patients ) . Treatment-related serious adverse events were reported in 12 ( 32 % ) patients in the ipilimumab every-12-weeks cohort and 11 ( 28 % ) patients in the every-6-weeks cohort . Treatment-related adverse events ( any grade ) prompted treatment discontinuation in four ( 11 % ) patients in the every-12-weeks cohort and five ( 13 % ) patients in the every-6-weeks cohort . No treatment-related deaths occurred . Confirmed objective responses were achieved in 18 ( 47 % [ 95 % CI 31 - 64 ] ) patients in the ipilimumab every-12-weeks cohort and 15 ( 38 % [ 95 % CI 23 - 55 ] ) patients in the ipilimumab every-6-weeks cohort ; median duration of response was not reached in either cohort , with median follow-up times of 12·8 months ( IQR 9·3 - 15·5 ) in the ipilimumab every-12-weeks cohort and 11·8 months ( 6·7 - 15·9 ) in the ipilimumab every-6-weeks cohort . In patients with PD-L1 of 1 % or greater , confirmed objective responses were achieved in 12 ( 57 % ) of 21 patients in the ipilimumab every-12-weeks cohort and 13 ( 57 % ) of 23 patients in the ipilimumab every-6-weeks cohort . INTERPRETATION In NSCLC , first-line nivolumab plus ipilimumab had a tolerable safety profile and showed encouraging clinical activity characterised by a high response rate and durable response . To our knowledge , the results of this study are the first suggestion of improved benefit compared with anti-PD-1 monotherapy in patients with NSCLC , supporting further assessment of this combination in a phase 3 study . FUNDING Bristol-Myers Squibb In this phase Ib study , four combination therapies of nivolumab 10 mg/kg and st and ard chemotherapy ( cisplatin/gemcitabine , cisplatin/pemetrexed , carboplatin/paclitaxel/bevacizumab , or docetaxel ) showed acceptable toxicity profiles in patients with advanced non-small-cell lung cancer . Furthermore , these combination therapies presented encouraging antitumor activities BACKGROUND Ipilimumab , an anti-CTLA4 monoclonal antibody , demonstrated survival benefit in melanoma with immune-related ( ir ) adverse events ( irAEs ) managed by the protocol -defined guidelines . This phase 2 study evaluated ipilimumab+paclitaxel (Taxol)/carboplatin in extensive-disease-small-cell lung cancer ( ED-SCLC ) . DESIGN Patients ( n=130 ) with chemotherapy-naïve ED-SCLC were r and omized 1 : 1 : 1 to receive paclitaxel ( 175 mg/m2)/carboplatin ( area under the curve=6 ) with either placebo ( control ) or ipilimumab 10 mg/kg in two alternative regimens , concurrent ipilimumab ( ipilimumab+paclitaxel/carboplatin followed by placebo+paclitaxel/carboplatin ) or phased ipilimumab ( placebo+paclitaxel/carboplatin followed by ipilimumab+paclitaxel/carboplatin ) . Treatment was administered every 3 weeks for a maximum of 18 weeks ( induction ) , followed by maintenance ipilimumab or placebo every 12 weeks . End points included progression-free survival ( PFS ) , irPFS , best overall response rate ( BORR ) ; irBORR , overall survival ( OS ) , and safety . RESULTS Phased ipilimumab , but not concurrent ipilimumab , improved irPFS versus control [ HR ( hazard ratio)=0.64 ; P=0.03 ] . No improvement in PFS ( HR=0.93 ; P=0.37 ) or OS ( HR=0.75 ; P=0.13 ) occurred . Phased ipilimumab , concurrent ipilimumab and control , respectively , were associated with median irPFS of 6.4 , 5.7 and 5.3 months ; median PFS of 5.2 , 3.9 and 5.2 months ; median OS of 12.9 , 9.1 and 9.9 months . Overall rates of grade 3/4 irAEs were 17 , 21 and 9 % for phased ipilimumab , concurrent ipilimumab and control , respectively . CONCLUSION These results suggest further investigation of ipilimumab in ED-SCLC Purpose Patients with extensive-stage disease small-cell lung cancer ( SCLC ) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum . This r and omized , double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC . Patients and Methods Patients were r and omly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum ( cisplatin or carboplatin ) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule ( chemotherapy in cycles one to four ; ipilimumab or placebo beginning in cycle three up to cycle six ) , followed by ipilimumab or placebo maintenance every 12 weeks . Primary end point was overall survival ( OS ) among patients receiving at least one dose of blinded study therapy . Results Of 1,132 patients r and omly assigned , 954 received at least one dose of study therapy ( chemotherapy plus ipilimumab , n = 478 ; chemotherapy plus placebo , n = 476 ) . Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo ( hazard ratio , 0.94 ; 95 % CI , 0.81 to 1.09 ; P = .3775 ) . Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo ( hazard ratio , 0.85 ; 95 % CI , 0.75 to 0.97 ) . Rates and severity of treatment-related adverse events were similar between arms , except for diarrhea , rash , and colitis , which were more frequent with chemotherapy plus ipilimumab . Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab ( 18 % v 2 % with chemotherapy plus placebo ) . Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo . Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC . No new or unexpected adverse events were observed with chemotherapy plus ipilimumab . Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC |
12,804 | 30,789,826 | Conclusion EPO administration in neonates with perinatal HIE reduces the risk of brain injury , cerebral palsy and cognitive impairment .
The evidence is limited to suggest its role as an adjuvant to hypothermia . | Abstract Background Erythropoietin ( EPO ) appears to confer neuroprotection to the injured brain .
R and omized clinical trials ( RCTs ) have demonstrated its safety in neonates with hypoxic-ischemic encephalopathy ( HIE ) ; however , the evidence is unclear .
The objective of this study was to examine the role of EPO in perinatal HIE by a systematic review and meta- analysis . | Background Therapeutic hypothermia reduces death and disability after moderate or severe neonatal encephalopathy in high-income countries and is used as st and ard therapy in these setting s. However , the safety and efficacy of cooling therapy in low- and middle-income countries ( LMICs ) , where 99 % of the disease burden occurs , remains unclear . We will examine whether whole body cooling reduces death or neurodisability at 18–22 months after neonatal encephalopathy , in LMICs . Methods We will r and omly allocate 408 term or near-term babies ( aged ≤ 6 h ) with moderate or severe neonatal encephalopathy admitted to public sector neonatal units in LMIC countries ( India , Bangladesh or Sri Lanka ) , to either usual care alone or whole-body cooling with usual care . Babies allocated to the cooling arm will have core body temperature maintained at 33.5 ° C using a servo-controlled cooling device for 72 h , followed by re-warming at 0.5 ° C per hour . All babies will have detailed infection screening at the time of recruitment and 3 Telsa cerebral magnetic resonance imaging and spectroscopy at 1–2 weeks after birth . Our primary endpoint is death or moderate or severe disability at the age of 18 months . Discussion Upon completion , HELIX will be the largest cooling trial in neonatal encephalopathy and will provide a definitive answer regarding the safety and efficacy of cooling therapy for neonatal encephalopathy in LMICs . The trial will also provide important data about the influence of co-existent perinatal infection on the efficacy of hypothermic neuroprotection . Trial registration Clinical Trials.gov , NCT02387385 . Registered on 27 February 2015 Background Exercise training is an integral component of evidence -based management programs for many chronic cardiac and respiratory conditions . Despite this , there are limited high- quality studies available on the significance of exercise training in pulmonary hypertension ( PH ) . The aim of this study is to evaluate the short and long-term effectiveness of exercise training in PH patients in terms of exercise capacity , quality of life , cardiac function and disease progression . Methods This r and omized control trial will aim to recruit 50 medically stable PH patients categorised as New York Heart Association functional classification II-III . Participants will be r and omly allocated to either the supervised exercise training group or usual care group for the 8-week study period . Exercise training will be conducted in an outpatient setting . Measurements at baseline and following the 8-week study period include exercise capacity ( 6 min walk distance and cardiopulmonary exercise test ) , cardiac function ( exercise cardiac magnetic resonance imaging [ CMRI ] and echocardiography ) , health-related quality of life ( Cambridge Pulmonary Hypertension Outcome Review ) , adverse responses to exercise training and time to clinical worsening . In addition , participants will be followed up for a minimum of 2 year period from commencement of the study so as to monitor long-term clinical outcomes i.e. time to clinical worsening . Discussion This study will determine whether an 8-week outpatient based supervised exercise training program is safe and beneficial for medically stable PH patients in the short and long term . This will be the first study to examine the impact of exercise training on right heart function using exercise CMRI . Results from the study will contribute new knowledge in relation to the impact of exercise training on cardiac function , long-term prognosis and inform clinical practice guidelines for this patient population . Moreover , the study will add to our underst and ing regarding the efficacy of exercise training in individuals with PH in an outpatient setting .Trial registration Australia and New Zeal and Clinical Trials Registry : ACTRN12616001467426 . Registered 21st October , 2016 OBJECTIVE : To determine if multiple doses of erythropoietin ( Epo ) administered with hypothermia improve neuroradiographic and short-term outcomes of newborns with hypoxic-ischemic encephalopathy . METHODS : In a phase II double-blinded , placebo-controlled trial , we r and omized newborns to receive Epo ( 1000 U/kg intravenously ; n = 24 ) or placebo ( n = 26 ) at 1 , 2 , 3 , 5 , and 7 days of age . All infants had moderate/severe encephalopathy ; perinatal depression ( 10 minute Apgar < 5 , pH < 7.00 or base deficit ≥15 , or resuscitation at 10 minutes ) ; and received hypothermia . Primary outcome was neurodevelopment at 12 months assessed by the Alberta Infant Motor Scale and Warner Initial Developmental Evaluation . Two independent observers rated MRI brain injury severity by using an established scoring system . RESULTS : The mean age at first study drug was 16.5 hours ( SD , 5.9 ) . Neonatal deaths did not significantly differ between Epo and placebo groups ( 8 % vs 19 % , P = .42 ) . Brain MRI at mean 5.1 days ( SD , 2.3 ) showed a lower global brain injury score in Epo-treated infants ( median , 2 vs 11 , P = .01 ) . Moderate/severe brain injury ( 4 % vs 44 % , P = .002 ) , subcortical ( 30 % vs 68 % , P = .02 ) , and cerebellar injury ( 0 % vs 20 % , P = .05 ) were less frequent in the Epo than placebo group . At mean age 12.7 months ( SD , 0.9 ) , motor performance in Epo-treated ( n = 21 ) versus placebo-treated ( n = 20 ) infants were as follows : Alberta Infant Motor Scale ( 53.2 vs 42.8 , P = .03 ) ; Warner Initial Developmental Evaluation ( 28.6 vs 23.8 , P = .05 ) . CONCLUSIONS : High doses of Epo given with hypothermia for hypoxic-ischemic encephalopathy may result in less MRI brain injury and improved 1-year motor function OBJECTIVE : To determine the safety and pharmacokinetics of erythropoietin ( Epo ) given in conjunction with hypothermia for hypoxic-ischemic encephalopathy ( HIE ) . We hypothesized that high dose Epo would produce plasma concentrations that are neuroprotective in animal studies ( ie , maximum concentration = 6000–10 000 U/L ; area under the curve = 117 000–140 000 U*h/L ) . METHODS : In this multicenter , open-label , dose-escalation , phase I study , we enrolled 24 newborns undergoing hypothermia for HIE . All patients had decreased consciousness and acidosis ( pH < 7.00 or base deficit ≥ 12 ) , 10-minute Apgar score ≤ 5 , or ongoing resuscitation at 10 minutes . Patients received 1 of 4 Epo doses intravenously : 250 ( N = 3 ) , 500 ( N = 6 ) , 1000 ( N = 7 ) , or 2500 U/kg per dose ( N = 8) . We gave up to 6 doses every 48 hours starting at < 24 hours of age and performed pharmacokinetic and safety analyses . RESULTS : Patients received mean 4.8 ± 1.2 Epo doses . Although Epo followed nonlinear pharmacokinetics , excessive accumulation did not occur during multiple dosing . At 500 , 1000 , and 2500 U/kg Epo , half-life was 7.2 , 15.0 , and 18.7 hours ; maximum concentration was 7046 , 13 780 , and 33 316 U/L , and total Epo exposure ( area under the curve ) was 50 306 , 131 054 , and 328 002 U*h/L , respectively . Drug clearance at a given dose was slower than reported in uncooled preterm infants . No deaths or serious adverse effects were seen . CONCLUSIONS : Epo 1000 U/kg per dose intravenously given in conjunction with hypothermia is well tolerated and produces plasma concentrations that are neuroprotective in animals . A large efficacy trial is needed to determine whether Epo add-on therapy further improves outcome in infants undergoing hypothermia for HIE OBJECTIVE Our aim was to compare the effectiveness of a one-month treatment with recombinant human erythropoietine ( rHuEpo ) according to the administration route . METHODS Retrospective study based on the data collection from medical files of 64 preterm infant hospitalized in the " institut de puériculture et de périnatalogie " ( Paris ) between January 13th , 2002 and April 13th , 2002 . The first group ( N = 33 ) was treated by subcutaneous rHuEpo 750 IU/kg per week , in three injections by week , for one month . The second group ( N = 15 ) was treated by continuous infusion of rHuEpo in total parenteral nutrition 1050 IU/kg per week ( 30 % augmentation to compensate the amount absorbed by the filter ) . The third group ( N = 16 ) received 750 IU/kg per week of rHuEpo in three direct intravenous injections . The effectiveness of rHuEpo was evaluated by the absolute reticulocyte count , the level of hemoglobin and the incidence of blood transfusion ( multiple logistic analysis of variant and regression ) . RESULTS The absolute reticulocyte count and hemoglobin level were significantly reduced after one month of treatment by continuous infusion of rHuEpo in total parenteral nutrition and direct intravenous injections compared with a one-month treatment by subcutaneous rHuEpo . Hemoglobine level were at 8.8 and 9.6 g/dl vs 10.3 g/dl ( P = 0.02 ) and absolute reticulocyte count at 123,000/mm3 and 190,000/mm3 vs 216,000/mm3 ( p = 0.001 ) . The number of transfused infants was significantly increased with utilization of continuous ( 40 % ) and direct intravenous ( 75 % ) compared with those treated by subcutaneous route ( 21.2 % ) while the ferritin level and phlebotomy losses were not significantly different in the three groups . The number of blood transfusion was significantly linked to phlebotomy losses and administration route of rHuEpo . CONCLUSION Our study tends to demonstrate that rHuEpo administered subcutaneously reduces significantly the number of transfusion in contrary to intravenous routes . Waiting for pilot study and new molecules , we recommend subcutaneous administration of rHuEpo to preterm infants 250 IU/kg three times weekly in the treatment of anemia of prematurity OBJECTIVE : The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy ( HIE ) , by using a r and omized , prospect i ve study design . METHODS : A total of 167 term infants with moderate/severe HIE were assigned r and omly to receive either erythropoietin ( N = 83 ) or conventional treatment ( N = 84 ) . Recombinant human erythropoietin , at either 300 U/kg ( N = 52 ) or 500 U/kg ( N = 31 ) , was administered every other day for 2 weeks , starting < 48 hours after birth . The primary outcome was death or disability . Neurodevelopmental outcomes were assessed at 18 months of age . RESULTS : Complete outcome data were available for 153 infants . Nine patients dropped out during treatment , and 5 patients were lost to follow-up monitoring . Death or moderate/severe disability occurred for 35 ( 43.8 % ) of 80 infants in the control group and 18 ( 24.6 % ) of 73 infants in the erythropoietin group ( P = .017 ) at 18 months . The primary outcomes were not different between the 2 erythropoietin doses . Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE ( P = .001 ) and not those with severe HIE ( P = .227 ) . No negative hematopoietic side effects were observed . CONCLUSION : Repeated , low-dose , recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE , without apparent side effects Abstract Objective : To determine the safety and efficacy of single dose systemic recombinant human erythropoietin ( rEPO ) in neonates with perinatal hypoxic Ischemic Encephalopathy ( HIE ) , and its effect on serum brain-derived neurotrophic factor ( BDNF ) and neuron-specific enolase ( NSE ) . Methods : Forty-five full-term neonates ; 30 with perinatal HIE and 15 controls were studied . HIE neonates were r and omized into three intervention groups ( first 6 h of life ) : 10 received single subcutaneous 1500 U/kg rEPO at day-1 , 10 subjected to hypothermia for 72 h and 10 received supportive care . BDNF and NSE measured during first 6 h and day 5 postnatal . Daily Thompson 's score , MRI brain and neuromuscular function scale for survivors at 3 months of age were done . Results : Hypothermia group had best survival especially with stage-II Sarnat scale , followed by rEpo and supportive group . BDNF day-5 was significantly higher in each group compared to controls . MRI score and neuromuscular function score were non-significantly lower in the hypothermia group compared to rEPO . Conclusions : Therapeutic hypothermia was superior to single dose rEpo for neuro-protection in HIE especially in patients with stage-II Sarnat scale . Therapeutic effect of combined rEPO multiple dosing and modest hypothermia therapy should be studied Background : Despite therapeutic hypothermia , neonates with encephalopathy ( NE ) have high rates of death or disability . Darbepoetin alfa ( Darbe ) has comparable biological activity to erythropoietin , but has extended circulating half-life ( t1/2 ) . Our aim was to determine Darbe safety and pharmacokinetics as adjunctive therapy to hypothermia . Study design : Thirty infants ( n = 10/arm ) ≥36 wk gestation undergoing therapeutic hypothermia for NE were r and omized to receive placebo , Darbe low dose ( 2 μg/kg ) , or high dose ( 10 μg/kg ) given intravenously within 12 h of birth ( first dose/hypothermia condition ) and at 7 d ( second dose/normothermia condition ) . Adverse events were documented for 1 mo . Serum sample s were obtained to characterize Darbe pharmacokinetics . Results : Adverse events ( hypotension , altered liver and renal function , seizures , and death ) were similar to placebo and historical controls . Following the first Darbe dose at 2 and 10 μg/kg , t1/2 was 24 and 32 h , and the area under the curve ( AUCinf ) was 26,555 and 180,886 h*mU/ml * , respectively . In addition , clearance was not significantly different between the doses ( 0.05 and 0.04 l/h ) . At 7 d , t1/2 was 26 and 35 h , and AUCinf was 10,790 and 56,233 h*mU/ml * , respectively ( * P < 0.01 ) . Conclusion : Darbe combined with hypothermia has similar safety profile to placebo with pharmacokinetics sufficient for weekly administration BACKGROUND Whether hypothermic therapy improves neurodevelopmental outcomes in newborn infants with asphyxial encephalopathy is uncertain . METHODS We performed a r and omized trial of infants who were less than 6 hours of age and had a gestational age of at least 36 weeks and perinatal asphyxial encephalopathy . We compared intensive care plus cooling of the body to 33.5 degrees C for 72 hours and intensive care alone . The primary outcome was death or severe disability at 18 months of age . Prespecified secondary outcomes included 12 neurologic outcomes and 14 other adverse outcomes . RESULTS Of 325 infants enrolled , 163 underwent intensive care with cooling , and 162 underwent intensive care alone . In the cooled group , 42 infants died and 32 survived but had severe neurodevelopmental disability , whereas in the noncooled group , 44 infants died and 42 had severe disability ( relative risk for either outcome , 0.86 ; 95 % confidence interval [ CI ] , 0.68 to 1.07 ; P=0.17 ) . Infants in the cooled group had an increased rate of survival without neurologic abnormality ( relative risk , 1.57 ; 95 % CI , 1.16 to 2.12 ; P=0.003 ) . Among survivors , cooling result ed in reduced risks of cerebral palsy ( relative risk , 0.67 ; 95 % CI , 0.47 to 0.96 ; P=0.03 ) and improved scores on the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development II ( P=0.03 for each ) and the Gross Motor Function Classification System ( P=0.01 ) . Improvements in other neurologic outcomes in the cooled group were not significant . Adverse events were mostly minor and not associated with cooling . CONCLUSIONS Induction of moderate hypothermia for 72 hours in infants who had perinatal asphyxia did not significantly reduce the combined rate of death or severe disability but result ed in improved neurologic outcomes in survivors . ( Current Controlled Trials number , IS RCT N89547571 . OBJECTIVE : Erythropoietin ( EPO ) is neuroprotective after asphyxia in animal studies . The efficacy and safety of EPO monotherapy in term neonates with hypoxic ischemic encephalopathy ( HIE ) is uncertain . STUDY DESIGN : Hundred term neonates with moderate or severe HIE were r and omized by r and om permuted block algorithm to receive either EPO 500 U kg‐1 per dose in 2 ml saline intravenously ( 50 neonates ) on alternate days for a total of five doses with the first dose given by 6 h of age ( treatment group ) or 2 ml of normal saline ( 50 neonates ) similarly for a total of five doses ( placebo group ) in a double‐blind study . No hypothermia was given . The primary outcome was combined end point of death or moderate or severe disability at mean age of 19 months ( s.d . , 0.61 ) . RESULTS : Death or moderate or severe disability occurred in 40 % of neonates in the treatment group vs 70 % in the placebo group ( risk ratio , 0.57 ; 95 % confidence interval ( CI ) 0.38 to 0.85 ; P = 0.003 ) . Death occurred in 16 % of patients in both the groups ( risk ratio , 1.0 ; 95 % CI 0.33 to 2.9 ; P = 0.61 ) . The risk of cerebral palsy was lower among survivors in the treatment group ( risk ratio , 0.52 ; 95 % CI 0.25 to 1.03 ; P = 0.04 ) and lesser number of babies were on anticonvulsants at assessment ( risk ratio , 0.47 ; 95 % CI 0.20 to 1.01 ; P = 0.03 ) . Neonatal brain magnetic resonance imaging showed more abnormalities in the placebo group ( relative risk , 0.66 ; 95 % CI 0.42 to 1.03 ; P = 0.04 ) ) . Improvement in other neurological outcomes was not significant . CONCLUSION : EPO monotherapy reduces the risk of death or disability in term neonates with moderate or severe encephalopathy BACKGROUND The aim of this study was to compare two neuroprotective strategies to supportive care in the treatment of perinatal asphyxia . METHODS A total of 67 term newborns with perinatal asphyxia were included and r and omized into three groups : one group received supportive treatment ; another group received a single dose of 40 mg/kg phenobarbital ; and the third received three daily doses of 1000 IU/kg erythropoietin . The following parameters were analyzed : gestational age , birthweight , Apgar scores , cord blood pH , total serum antioxidant status ( TAS ) , superoxide dismutase ( SOD ) , glutathione peroxidase ( GPx ) and malondialdehyde ( MDA ) . The newborns were included in the follow-up program and examined up to 18 months of age . RESULTS TAS was higher in the erythropoietin group than in the other groups . SOD and GPx were lower for infants treated with phenobarbital or erythropoietin compared to control infants . MDA was lower in the erythropoietin group compared to the other groups , although the difference was not statistically significant ( P > 0.05 ) . The mortality rate was lower in the phenobarbital and erythropoietin groups ( both 4.6 % ) than in the control group ( 17.4 % ) . Long-term neurologic follow up showed a high incidence of sequelae in the control group compared to the phenobarbital and erythropoietin groups . Follow-up results were better in the phenobarbital group than in the erythropoietin group for motor and cognitive function at 3 and 6 months and worse for expressive language . At 18 months , however , the differences between these two groups were not significant . CONCLUSION High-dose phenobarbital or erythropoietin along with supportive treatment has a positive influence on the outcome of newborns with perinatal asphyxia . Phenobarbital has the advantage of low cost and simplicity |
12,805 | 31,237,554 | CONCLUSION MSCs treatment showed favorable impact on LVEF , NYHA classification , LVEDd , and the proportion of fixed defects for cardiomyopathy patients | INTRODUCTION The efficacy of mesenchymal stem cells ( MSCs ) for cardiomyopathy remains controversial .
We conducted a systematic review and meta- analysis to explore the influence of MSCs versus placebo on the treatment efficacy of cardiomyopathy . | Background —Intracoronary administration of bone marrow – derived progenitor cells ( BMC ) was shown to improve coronary microvascular function in ischemic heart disease . Because coronary microvascular dysfunction is implicated in the pathogenesis and prognosis of nonischemic dilated cardiomyopathy ( DCM ) , we investigated the effects of intracoronary BMC administration in patients with DCM . Methods and Results —Intracoronary infusion of BMC was performed in 33 patients with DCM by using an over-the-wire balloon catheter . Left ventricular contractility at baseline and after 3 months was assessed by analysis of left ventricular angiograms . Coronary hemodynamics were determined by intracoronary Doppler wire measurements . After 3 months , regional wall motion of the target area ( contractility from −1.08±0.39 to −0.97±0.47 SD/chord , P=0.029 ) and global left ventricular ejection fraction ( from 30.2±10.9 to 33.4±11.5 % , P<0.001 ) were improved . Increase of regional contractile function was directly related to the functionality of the infused cells as measured by their colony-forming capacity . Minimal vascular resistance index was significantly reduced in the BMC -treated vessel after 3 months ( from 1.53±0.63 to 1.32±0.61 mm Hg · s/cm ; P=0.002 , n=24 ) , whereas no changes were observed in the reference vessel ( from 1.60±0.45 to 1.49±0.45 mm Hg · s/cm ; P=0.133 , n=13 ) . Twelve months after BMC infusion , N-terminal prohormone brain natriuretic peptide ( NT-proBNP ) serum levels were decreased , suggesting a beneficial effect on left ventricular remodeling processes ( from 1610±993 to 1473±1147 pg/mL ; P=0.038 for logNT-proBNP , n=26 ) . Conclusions —Intracoronary administration of BMC seems to be associated with improvements in cardiac contractile and microvascular function in patients with DCM . Thus , r and omized blinded studies are warranted to evaluate potential clinical benefits of intracoronary BMC administration in patients with DCM 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 Aims Intracoronary infusion of autologous nucleated bone marrow cells ( BMC s ) enhanced the recovery of left ventricular ejection fraction ( LVEF ) after ST-segment elevation myocardial infa rct ion ( STEMI ) in the r and omised-controlled , open-label BOOST trial . We reassessed the therapeutic potential of nucleated BMC s in the r and omised placebo-controlled , double-blind BOOST-2 trial conducted in 10 centres in Germany and Norway . Methods and results Using a multiple arm design , we investigated the dose-response relationship and explored whether γ-irradiation which eliminates the clonogenic potential of stem and progenitor cells has an impact on BMC efficacy . Between 9 March 2006 and 16 July 2013 , 153 patients with large STEMI were r and omly assigned to receive a single intracoronary infusion of placebo ( control group ) , high-dose ( hi ) BMC s , low-dose ( lo ) BMC s , irradiated hi BMC s , or irradiated lo BMC s 8.1 ± 2.6 days after percutaneous coronary intervention ( PCI ) in addition to guideline -recommended medical treatment . Change in LVEF from baseline ( before cell infusion ) to 6 months as determined by MRI was the primary endpoint . The trial is registered at Current Controlled Trials ( IS RCT N17457407 ) . Baseline LVEF was 45.0 ± 8.5 % in the overall population . At 6 months , LVEF had increased by 3.3 percentage points in the control group and 4.3 percentage points in the hi BMC group . The estimated treatment effect was 1.0 percentage points ( 95 % confidence interval , -2.6 to 4.7 ; P = 0.57 ) . The treatment effect of lo BMC s was 0.5 percentage points ( -3.0 to 4.1 ; P = 0.76 ) . Likewise , irradiated BMC s did not have significant treatment effects . BMC transfer was safe and not associated with adverse clinical events . Conclusion The BOOST-2 trial does not support the use of nucleated BMC s in patients with STEMI and moderately reduced LVEF treated according to current st and ards of early PCI and drug therapy Rationale : Transcatheter , intramyocardial injections of bone marrow – derived cell therapy produces reverse remodeling in large animal models of ischemic cardiomyopathy . Objective : We used cardiac MRI ( CMR ) in patients with left ventricular ( LV ) dysfunction related to remote myocardial infa rct ion ( MI ) to test the hypothesis that bone marrow progenitor cell injection causes functional recovery of scarred myocardium and reverse remodeling . Methods and Results : Eight patients ( aged 57.2±13.3 years ) received transendocardial , intramyocardial injection of autologous bone marrow progenitor cells ( mononuclear or mesenchymal stem cells ) in LV scar and border zone . All patients tolerated the procedure with no serious adverse events . CMR at 1 year demonstrated a decrease in end diastolic volume ( 208.7±20.4 versus 167.4±7.32 mL ; P=0.03 ) , a trend toward decreased end systolic volume ( 142.4±16.5 versus 107.6±7.4 mL ; P=0.06 ) , decreased infa rct size ( P<0.05 ) , and improved regional LV function by peak Eulerian circumferential strain in the treated infa rct zone ( −8.1±1.0 versus −11.4±1.3 ; P=0.04 ) . Improvements in regional function were evident at 3 months , whereas the changes in chamber dimensions were not significant until 6 months . Improved regional function in the infa rct zone strongly correlated with reduction of end diastolic volume ( r2=0.69 , P=0.04 ) and end systolic volume ( r2=0.83 , P=0.01 ) . Conclusions : These data suggest that transcatheter , intramyocardial injections of autologous bone marrow progenitor cells improve regional contractility of a chronic myocardial scar , and these changes predict subsequent reverse remodeling . The findings support the potential clinical benefits of this new treatment strategy and ongoing r and omized clinical trials The aim of this study was to determine if bone marrow mononuclear cell ( BMMC ) transplantation is safe for moderate to severe idiopathic dilated cardiomyopathy ( IDC ) . Clinical trials have shown that this procedure is safe and effective for ischemic patients , but little information is available regarding non-ischemic patients . Twenty-four patients with IDC , optimized therapy , age 46 ± 11.6 years , 17 males , NYHA classes II-IV , and left ventricular ejection fraction < 35 % were enrolled in the study . Clinical evaluation at baseline and 6 months after stem cell therapy to assess heart function included echocardiogram , magnetic resonance imaging , cardiopulmonary test , Minnesota Quality of Life Question naire , and NYHA classification . After cell transplantation 1 patient showed a transient increase in enzyme levels and 2 patients presented arrhythmias that were reversed within 72 h. Four patients died during follow-up , between 6 and 12 weeks after therapy . Clinical evaluation showed improvement in most patients as reflected by statistically significant decreases in Minnesota Quality of Life Question naire ( 63 ± 17.9 baseline vs 28.8 ± 16.75 at 6 months ) and in class III-IV NYHA patients ( 18/24 baseline vs 2/20 at 6 months ) . Cardiopulmonary exercise tests demonstrated increased peak oxygen consumption ( 12.2 ± 2.4 at baseline vs 15.8 ± 7.1 mL·kg⁻¹·min⁻¹ at 6 months ) and walked distance ( 377.2 ± 85.4 vs 444.1 ± 77.9 m at 6 months ) in the 6-min walk test , which was not accompanied by increased left ventricular ejection fraction . Our findings indicate that BMMC therapy in IDC patients with severe ventricular dysfunction is feasible and that larger , r and omized and placebo-controlled trials are warranted BACKGROUND the objective of the study was to determine whether the effects of infa rct -related artery ( IRA ) infusion of autologous bone marrow-derived CD34(+ ) cells after ST elevation myocardial infa rct ion ( STEMI ) are dependent on the dose ( quantity and mobility ) of the cells infused . Beneficial effects of IRA infusion of mononuclear cells after STEMI have been inconsistent , possibly because of differences in timing , cell type , quantity , and mobility of infused cells . METHODS patients were r and omized to bone marrow harvest ( n = 16 ) or control ( n = 15 ) . At a median of 8.3 days after coronary stenting for STEMI , CD34(+ ) cells were infused via the IRA at 3 dose levels ( 5 , 10 , and 15 × 10(6 ) ) in cohorts of 5 patients each . Baseline and follow-up imaging and ex vivo CD34(+ ) cell mobility were performed . RESULTS Cell harvest and infusion were safe . Quantitative rest hypoperfusion score measured by single-photon emission computed tomography improved at 6 months in the ≥ 10 million cohorts compared with controls ( -256 vs + 14 , P = .02 ) . There was a trend toward improved ejection fraction at 6 months ( + 4.5 % ) in the ≥ 10 million cohorts compared with no change in the controls and 5 million cohort ( + 0.7 % ) . Improved perfusion and infa rct size reduction correlated with the quantity and mobility of the infused CD34(+ ) cells . CONCLUSIONS the effects of CD34(+ ) cell IRA infusion during the repair phase after STEMI are dose dependent and , at a threshold dose of 10 million CD34(+ ) cells , associated with a significant improvement in perfusion that may limit deterioration in cardiac function ( IRA infusion of CD34(+ ) cells in patients with acute myocardial infa rct ion [ AMR-01 ] NCT00313339 ) AIMS Comparison of intracoronary infusion of bone marrow (BM)-derived unselected mononuclear cells ( UNSEL ) and selected CD34(+)CXCR4(+ ) cells ( SEL ) in patients with acute myocardial infa rct ion ( AMI ) and reduced < 40 % left ventricular ejection fraction ( LVEF ) . METHODS AND RESULTS Two hundred patients were r and omized to intracoronary infusion of UNSEL ( n = 80 ) or SEL ( n = 80 ) BM cells or to the control ( CTRL ) group without BM cell treatment . Primary endpoint : change of LVEF and volumes measured by magnetic resonance imaging before and 6 months after the procedure . After 6 months , LVEF increased by 3 % ( P = 0.01 ) in patients treated with UNSEL , 3 % in patients receiving SEL ( P = 0.04 ) and remained unchanged in CTRL group ( P = 0.73 ) . There were no significant differences in absolute changes of LVEF between the groups . Absolute changes of left ventricular end-systolic volume and left ventricular end-diastolic volume were not significantly different in all groups . Significant increase of LVEF was observed only in patients treated with BM cells who had baseline LVEF < median ( 37 % ) . Baseline LVEF < median and time from the onset of symptoms to primary percutaneous coronary intervention > or = median were predictors of LVEF improvement in patients receiving BM cells . There were no differences in major cardiovascular event ( death , re-infa rct ion , stroke , target vessel revascularization ) between groups . CONCLUSION In patients with AMI and impaired LVEF , treatment with BM cells does not lead to a significant improvement of LVEF or volumes . There was however a trend in favour of cell therapy in patients with most severely impaired LVEF and longer delay between the symptoms and revascularization BACKGROUND Emerging evidence suggests that stem cells and progenitor cells derived from bone marrow can be used to improve cardiac function in patients after acute myocardial infa rct ion . In this r and omised trial , we aim ed to assess whether intracoronary transfer of autologous bone-marrow cells could improve global left-ventricular ejection fraction ( LVEF ) at 6 months ' follow-up . METHODS After successful percutaneous coronary intervention ( PCI ) for acute ST-segment elevation myocardial infa rct ion , 60 patients were r and omly assigned to either a control group ( n=30 ) that received optimum postinfa rct ion medical treatment , or a bone-marrow-cell group ( n=30 ) that received optimum medical treatment and intracoronary transfer of autologous bone-marrow cells 4.8 days ( SD 1.3 ) after PCI . Primary endpoint was global left-ventricular ejection fraction ( LVEF ) change from baseline to 6 months ' follow-up , as determined by cardiac MRI . Image analyses were done by two investigators blinded for treatment assignment . Analysis was per protocol . FINDINGS Global LVEF at baseline ( determined 3.5 days [ SD 1.5 ] after PCI ) was 51.3 ( 9.3 % ) in controls and 50.0 ( 10.0 % ) in the bone-marrow cell group ( p=0.59 ) . After 6 months , mean global LVEF had increased by 0.7 percentage points in the control group and 6.7 percentage points in the bone-marrow-cell group ( p=0.0026 ) . Transfer of bone-marrow cells enhanced left-ventricular systolic function primarily in myocardial segments adjacent to the infa rct ed area . Cell transfer did not increase the risk of adverse clinical events , in-stent restenosis , or proarrhythmic effects . INTERPRETATION Intracoronary transfer of autologous bone-marrow-cells promotes improvement of left-ventricular systolic function in patients after acute myocardial infa rct ion OBJECTIVE Recent experimental and clinical observations have suggested that cell transplantation could be of therapeutic value for the treatment of heart failure . This study was performed to explore the efficacy and safety of intracoronary autologous mesenchymal stem cells ( MSCs ) transplantation for treating patients with idiopathic dilated cardiomyopathy . METHOD Twenty-four consecutive patients with idiopathic dilated cardiomyopathy received st and ard drug therapy were r and omly divided into intracoronary injection of autologous mesenchymal stem cells ( treated , n = 12 ) or saline ( control , n = 12 ) groups . Serum IL-6 , TNF-alpha and CRP , plasma brain natriuretic peptides ( BNP ) were determined and echocardiography , Holter electrocardiogram monitoring and six minutes walk test were performed at baseline , 3 and 6 months post injection . RESULTS IL-6 , TNF-alpha and CRP remained unchanged after MSCs transplantation . Plasma BNP levels at 3 months and 6 months post MSCs injection were significantly higher than that of pre-injection ( 378.10 + /- 147.47 , 420.40 + /- 148.50 vs. 292.40 + /- 148.54 ng/L , respectively , P < 0.05 ) but were significantly lower than that in control group at comparable time points ( 3 months : 378.10 + /- 147.47 vs. 473.10 + /- 106.31 ng/L ; 6 months : 420.40 + /- 148.50 vs. 544.60 + /- 93.11 ng/L , P < 0.05 ) . Six-minute-walking distance significantly increased at 6 months after MSCs injection compared with pre-injection level and which is also higher than that in control patients ( 519.00 + /- 43.28 vs. 396.33 + /- 42.19 and 464.00 + /- 76.5 m , respectively , P < 0.05 ) . Left ventricular ejection fraction and LVEDd remained unchanged post MSCs injection . No malignant arrhythmias and severe side effects could be observed around transplantation and during six months follow-up . Survival was similar between the two groups during six months follow-up . CONCLUSION Percutaneous coronary autologous mesenchymal stem cells transplantation can attenuate the increase of plasma BNP , increase six-minute-walking capacity in patients with idiopathic dilated cardiomyopathy IMPORTANCE Whether culture-exp and ed mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial . OBJECTIVE To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells ( MSCs ) and bone marrow mononuclear cells ( BMC s ) in patients with ischemic cardiomyopathy . DESIGN , SETTING , AND PATIENTS A phase 1 and 2 r and omized , blinded , placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular ( LV ) ejection fraction less than 50 % ( September 1 , 2009-July 12 , 2013 ) . The study compared injection of MSCs ( n=19 ) with placebo ( n = 11 ) and BMC s ( n = 19 ) with placebo ( n = 10 ) , with 1 year of follow-up . INTERVENTIONS Injections in 10 LV sites with an infusion catheter . MAIN OUTCOMES AND MEASURES Treatment-emergent 30-day serious adverse event rate defined as a composite of death , myocardial infa rct ion , stroke , hospitalization for worsening heart failure , perforation , tamponade , or sustained ventricular arrhythmias . RESULTS No patient had a treatment-emergent serious adverse events at day 30 . The 1-year incidence of serious adverse events was 31.6 % ( 95 % CI , 12.6 % to 56.6 % ) for MSCs , 31.6 % ( 95 % CI , 12.6%-56.6 % ) for BMC s , and 38.1 % ( 95 % CI , 18.1%-61.6 % ) for placebo . Over 1 year , the Minnesota Living With Heart Failure score improved with MSCs ( -6.3 ; 95 % CI , -15.0 to 2.4 ; repeated measures of variance , P=.02 ) and with BMC s ( -8.2 ; 95 % CI , -17.4 to 0.97 ; P=.005 ) but not with placebo ( 0.4 ; 95 % CI , -9.45 to 10.25 ; P=.38 ) . The 6-minute walk distance increased with MSCs only ( repeated measures model , P = .03 ) . Infa rct size as a percentage of LV mass was reduced by MSCs ( -18.9 % ; 95 % CI , -30.4 to -7.4 ; within-group , P = .004 ) but not by BMC s ( -7.0 % ; 95 % CI , -15.7 % to 1.7 % ; within-group , P = .11 ) or placebo ( -5.2 % ; 95 % CI , -16.8 % to 6.5 % ; within-group , P = .36 ) . Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs ( -4.9 ; 95 % CI , -13.3 to 3.5 ; within-group repeated measures , P = .03 ) but not BMC s ( -2.1 ; 95 % CI , -5.5 to 1.3 ; P = .21 ) or placebo ( -0.03 ; 95 % CI , -1.9 to 1.9 ; P = .14 ) . Left ventricular chamber volume and ejection fraction did not change . CONCLUSIONS AND RELEVANCE Transendocardial stem cell injection with MSCs or BMC s appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction . Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect , these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00768066 OBJECTIVE To compare the effects of intracoronary infusion of mononuclear stem cells ( MNCs ) or mesenchymal stem cells ( MSCs ) in patients with dilated cardiomyopathy ( DCM ) . METHODS DCM patients with left ventricular ejection fraction(LVEF ) < 40 % were r and omized to intracoronary infusion of MNCs [ ( 5.1 ± 2.0 ) × 10(8 ) , n = 16 ] or MSCs [ ( 4.9 ± 1.7 ) × 10(8 ) , n = 17 ] or equal volume normal saline ( n = 20 ) through the guiding catheter . Changes of left ventricular end-diastolic diameter ( LVEDd ) , LVEF and myocardium perfusion defects were assessed before and at ( 30 ± 3 ) days and ( 90 ± 7 ) days after the procedure . Malignant cardiovascular events were also recorded . RESULTS ( 1 ) One month after the procedure , LVEF in transplantation groups significantly increased compared to before procedure ( all P < 0.05 ) , and significant increase of LVEF was observed only in MSCs transplantation group compared to control group ( P < 0.05 ) . However , absolute changes of LVEDd and perfusion defects of myocardium were similar among and within groups ( P > 0.05 ) . ( 2 ) Comparing with before procedure and control group , LVEF in transplantation groups increased significantly in three months after the procedure ( P < 0.05 ) , but there were no significant differences between transplantation groups ( P > 0.05 ) . LVEDd and myocardium perfusion defects in transplantation groups improved significantly compared with that of before procedure ( P < 0.05 ) , while significant decrease of myocardium perfusion defects was only observed in patients treated with MSCs compared with control group at three months after procedure ( P < 0.05 ) . ( 3 ) There were no significant differences in major cardiovascular events between transplantation group and control during follow-up ( P > 0.05 ) . CONCLUSIONS Intracoronary bone marrow stem cells transplantation is safe and effective for DCM patients while the efficacy of MSCs and MNCs transplantation is comparable Stem cell therapy has shown therapeutic benefit in dilated cardiomyopathy ( DCM ) , but doubt remains about the most appropriate stem cell sub population . The current study compared the efficacy of intracoronary administration of bone marrow mononuclear cells ( BMMC ) or mesenchymal stem cells ( BMSC ) in patients with DCM.Fifty-three patients with DCM and reduced ( < 40 % ) left ventricular ejection fraction ( LVEF ) , were r and omized to intracoronary infusion of BMMC ( BMMC group , n = 16 ) or BMSC ( BMSC group , n = 17 ) or equal volume normal saline ( CTRL group , n = 20 ) . LVEF , New York Heart Association ( NYHA ) class , left ventricular end-diastolic diameter ( LVEDd ) , and myocardial perfusion were assessed at baseline and at 3-month and 12-month follow-ups . Major adverse cardiovascular events ( MACE ) were also recorded . At the 3-month follow-up , LVEF , NYHA class , and myocardial perfusion had improved significantly in the BMSC group ( P = 0.004 , 0.020 and 0.019 , respectively ) along with significant changes in LVEF and NYHA class in the BMMC group compared with CTRL ( P = 0.042 and 0.047 , respectively ) , however , LVEDd remained unchanged . In comparison with CTRL , LVEF , NYHA class , and myocardial perfusion improved significantly in the BMSC group at the 12-month follow-up ( P = 0.005 , 0.050 and 0.038 respectively ) , but not in the BMMC group ( P > 0.05 ) . There were no significant differences between the transplantation groups during follow-up ( P > 0.05 ) . There were no differences in MACE among the 3 groups ( P = 0.817).Intracoronary bone marrow stem cell transplantation in DCM is safe and effective , while BMSC and BMMC infusion possess comparable effectiveness BACKGROUND We investigated clinical effects of intracoronary transplantation of CD34 + cells in patients with dilated cardiomyopathy ( DCM ) . METHODS Of 55 patients with DCM , 28 were r and omized to CD34 + transplantation ( SC group ) , and 27 patients did not receive stem cell therapy ( controls ) . In the SC group , peripheral blood CD34 + cells were mobilized by granulocyte-colony stimulating factor and collected via apheresis . Patients underwent myocardial scintigraphy and CD34 + cells were injected in the coronary artery supplying the segments with reduced viability . RESULTS At baseline , the 2 groups did not differ in age , gender , left ventricular ejection fraction ( LVEF ) , or NT-proBNP levels . At 1 year , stem cell therapy was associated with an increase in LVEF ( from 25.5 ± 7.5 % to 30.1 ± 6.7 % ; P = .03 ) , an increase in 6-minute walk distance ( from 359 ± 104 m to 485 ± 127 m ; P = .001 ) , and a decrease in NT-proBNP ( from 2069 ± 1996 pg/mL to 1037 ± 950 pg/mL ; P = .01 ) . The secondary endpoint of 1-year mortality or heart transplantation was lower in patients receiving SC therapy ( 2/28 , 7 % ) than in controls ( 8/27 , 30 % ) ( P = .03 ) , and SC therapy was the only independent predictor of outcome on multivariable analysis ( P = .04 ) . CONCLUSIONS Intracoronary stem cell transplantation could lead to improved ventricular remodeling , better exercise tolerance and potentially improved survival in patients with DCM BACKGROUND Limited data is available for investigating the long-term safety and effects of intracoronary progenitor cell therapy in patients with acute myocardial infa rct ion ( AMI ) . OBJECTIVE To assess the clinical course , NT-proBNP and MRI data as objective markers of cardiac function of the TOPCARE-AMI patients at 5-year follow-up . DESIGN The TOPCARE-AMI trial was the first r and omized study investigating the effects of intracoronary infusion of circulating ( CPC ) or bone marrow-derived progenitor cells ( BMC ) in 59 patients with successfully reperfused AMI . RESULTS Five-year follow-up data were completed in 55 patients , 3 patients were lost to follow-up . None of the patients showed any signs of intramyocardial calcification or tumors at 5 years . One patient died during the initial hospitalization , no patient was rehospitalized for heart failure and 16 patients underwent target vessel revascularization ( TVR ) . Only two TVRs occurred later than 1 year after cell administration making it very unlikely that the infused cells accelerate atherosclerotic disease progression . Serum levels of NT-proBNP remained significantly reduced at the 5-year follow-up indicating the absence of heart failure . MRI subgroup analysis in 31 patients documented a persistent improvement of LV ejection fraction ( from 46 ± 10 % at baseline to 57 ± 10 % at 5 years , p < 0.001 ) ) . Simultaneously , there was a reduction ( p < 0.001 ) in functional infa rct size measured as late enhancement volume normalized to LV mass . However , whereas LV end-systolic volume remained stable , LV end-diastolic volume increased significantly . CONCLUSIONS The 5-year follow-up of the TOPCARE-AMI trial provides reassurance with respect to the long-term safety of intracoronary cell therapy and suggests favorable effects on LV function CONTEXT Previous studies using autologous bone marrow mononuclear cells ( BMC s ) in patients with ischemic cardiomyopathy have demonstrated safety and suggested efficacy . OBJECTIVE To determine if administration of BMC s through transendocardial injections improves myocardial perfusion , reduces left ventricular end-systolic volume ( LVESV ) , or enhances maximal oxygen consumption in patients with coronary artery disease or LV dysfunction , and limiting heart failure or angina . DESIGN , SETTING , AND PATIENTS A phase 2 r and omized double-blind , placebo-controlled trial of symptomatic patients ( New York Heart Association classification II-III or Canadian Cardiovascular Society classification II-IV ) with a left ventricular ejection fraction of 45 % or less , a perfusion defect by single-photon emission tomography ( SPECT ) , and coronary artery disease not amenable to revascularization who were receiving maximal medical therapy at 5 National Heart , Lung , and Blood Institute-sponsored Cardiovascular Cell Therapy Research Network ( CCTRN ) sites between April 29 , 2009 , and April 18 , 2011 . INTERVENTION Bone marrow aspiration ( isolation of BMC s using a st and ardized automated system performed locally ) and transendocardial injection of 100 million BMC s or placebo ( ratio of 2 for BMC group to 1 for placebo group ) . MAIN OUTCOME MEASURES Co- primary end points assessed at 6 months : changes in LVESV assessed by echocardiography , maximal oxygen consumption , and reversibility on SPECT . Phenotypic and functional analyses of the cell product were performed by the CCTRN biorepository core laboratory . RESULTS Of 153 patients who provided consent , a total of 92 ( 82 men ; average age : 63 years ) were r and omized ( n = 61 in BMC group and n = 31 in placebo group ) . Changes in LVESV index ( -0.9 mL/m(2 ) [ 95 % CI , -6.1 to 4.3 ] ; P = .73 ) , maximal oxygen consumption ( 1.0 [ 95 % CI , -0.42 to 2.34 ] ; P = .17 ) , and reversible defect ( -1.2 [ 95 % CI , -12.50 to 10.12 ] ; P = .84 ) were not statistically significant . There were no differences found in any of the secondary outcomes , including percent myocardial defect , total defect size , fixed defect size , regional wall motion , and clinical improvement . CONCLUSION Among patients with chronic ischemic heart failure , transendocardial injection of autologous BMC s compared with placebo did not improve LVESV , maximal oxygen consumption , or reversibility on SPECT . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00824005 BACKGROUND Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow ( BMC ) or circulating blood ( CPC ) may improve left ventricular function after acute myocardial infa rct ion . The effects of cell transplantation in patients with healed myocardial infa rct ion are unknown . METHODS After an initial pilot trial involving 17 patients , we r and omly assigned , in a controlled crossover study , 75 patients with stable ischemic heart disease who had had a myocardial infa rct ion at least 3 months previously to receive either no cell infusion ( 23 patients ) or infusion of CPC ( 24 patients ) or BMC ( 28 patients ) into the patent coronary artery supplying the most dyskinetic left ventricular area . The patients in the control group were subsequently r and omly assigned to receive CPC or BMC , and the patients who initially received BMC or CPC crossed over to receive CPC or BMC , respectively , at 3 months ' follow-up . RESULTS The absolute change in left ventricular ejection fraction was significantly greater among patients receiving BMC ( + 2.9 percentage points ) than among those receiving CPC ( -0.4 percentage point , P=0.003 ) or no infusion ( -1.2 percentage points , P<0.001 ) . The increase in global cardiac function was related to significantly enhanced regional contractility in the area targeted by intracoronary infusion of BMC . The crossover phase of the study revealed that intracoronary infusion of BMC was associated with a significant increase in global and regional left ventricular function , regardless of whether patients crossed over from control to BMC or from CPC to BMC . CONCLUSIONS Intracoronary infusion of progenitor cells is safe and feasible in patients with healed myocardial infa rct ion . Transplantation of BMC is associated with moderate but significant improvement in the left ventricular ejection fraction after 3 months |
12,806 | 29,164,603 | Although sensitivity was good in one included study , considering the poor specificity and the limited data available in the literature , we can not recommend routine use of 18F-florbetapir PET in clinical practice to predict the progression from MCI to ADD.Because of the poor sensitivity and specificity , limited number of included participants , and the limited data available in the literature , we can not recommend its routine use in clinical practice to predict the progression from MCI to any form of dementia . | BACKGROUND 18F-florbetapir uptake by brain tissue measured by positron emission tomography ( PET ) is accepted by regulatory agencies like the Food and Drug Administration ( FDA ) and the European Medicine Agencies ( EMA ) for assessing amyloid load in people with dementia .
Its added value is mainly demonstrated by excluding Alzheimer 's pathology in an established dementia diagnosis .
However , the National Institute on Aging and Alzheimer 's Association ( NIA-AA ) revised the diagnostic criteria for Alzheimer 's disease and confidence in the diagnosis of mild cognitive impairment ( MCI ) due to Alzheimer 's disease may be increased when using amyloid biomarkers tests like 18F-florbetapir .
These tests , added to the MCI core clinical criteria , might increase the diagnostic test accuracy ( DTA ) of a testing strategy .
However , the DTA of 18F-florbetapir to predict the progression from MCI to Alzheimer 's disease dementia ( ADD ) or other dementias has not yet been systematic ally evaluated .
OBJECTIVES To determine the DTA of the 18F-florbetapir PET scan for detecting people with MCI at time of performing the test who will clinical ly progress to ADD , other forms of dementia ( non-ADD ) , or any form of dementia at follow-up . | An 18F-labeled PET amyloid-β ( Aβ ) imaging agent could facilitate the clinical evaluation of late-life cognitive impairment by providing an objective measure for Alzheimer disease ( AD ) pathology . Here we present the results of a clinical trial with (E)-4-(2-(6-(2-(2-(2 - 18F-fluoroethoxy)ethoxy)ethoxy)pyridin-3-yl)vinyl)-N-methyl benzenamine ( 18F-AV-45 or flobetapir F 18 ) . Methods : An open-label , multicenter brain imaging , metabolism , and safety study of 18F-AV-45 was performed on 16 patients with AD ( Mini-Mental State Examination score , 19.3 ± 3.1 ; mean age ± SD , 75.8 ± 9.2 y ) and 16 cognitively healthy controls ( HCs ) ( Mini-Mental State Examination score , 29.8 ± 0.45 ; mean age ± SD , 72.5 ± 11.6 y ) . Dynamic PET was performed over a period of approximately 90 min after injection of the tracer ( 370 MBq [ 10 mCi ] ) . St and ardized uptake values and cortical-to-cerebellum st and ardized uptake value ratios ( SUVRs ) were calculated . A simplified reference tissue method was used to generate distribution volume ratio ( DVR ) parametric maps for a subset of subjects . Results : Valid PET data were available for 11 AD patients and 15 HCs . 18F-AV-45 accumulated in cortical regions expected to be high in Aβ deposition ( e.g. , precuneus and frontal and temporal cortices ) in AD patients ; minimal accumulation of the tracer was seen in cortical regions of HCs . The cortical-to-cerebellar SUVRs in AD patients showed continual substantial increases through 30 min after administration , reaching a plateau within 50 min . The 10-min period from 50 to 60 min after administration was taken as a representative sample for further analysis . The cortical average SUVR for this period was 1.67 ± 0.175 for patients with AD versus 1.25 ± 0.177 for HCs . Spatially normalized DVRs generated from PET dynamic scans were highly correlated with SUVR ( r = 0.58–0.88 , P < 0.005 ) and were significantly greater for AD patients than for HCs in cortical regions but not in subcortical white matter or cerebellar regions . No clinical ly significant changes in vital signs , electrocardiogram , or laboratory values were observed . Conclusion : 18F-AV-45 was well tolerated , and PET showed significant discrimination between AD patients and HCs , using either a parametric reference region method ( DVR ) or a simplified SUVR calculated from 10 min of scanning 50–60 min after 18F-AV-45 administration BACKGROUND Subjects with a mild cognitive impairment ( MCI ) have a memory impairment beyond that expected for age and education yet are not demented . These subjects are becoming the focus of many prediction studies and early intervention trials . OBJECTIVE To characterize clinical ly subjects with MCI cross-sectionally and longitudinally . DESIGN A prospect i ve , longitudinal inception cohort . SETTING General community clinic . PARTICIPANTS A sample of 76 consecutively evaluated subjects with MCI were compared with 234 healthy control subjects and 106 patients with mild Alzheimer disease ( AD ) , all from a community setting as part of the Mayo Clinic Alzheimer 's Disease Center/Alzheimer 's Disease Patient Registry , Rochester , Minn. MAIN OUTCOME MEASURES The 3 groups of individuals were compared on demographic factors and measures of cognitive function including the Mini-Mental State Examination , Wechsler Adult Intelligence Scale-Revised , Wechsler Memory Scale-Revised , Dementia Rating Scale , Free and Cued Selective Reminding Test , and Auditory Verbal Learning Test . Clinical classifications of dementia and AD were determined according to the Diagnostic and Statistical Manual of Mental Disorders , Revised Third Edition and the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer 's Disease and Related Disorders Association criteria , respectively . RESULTS The primary distinction between control subjects and subjects with MCI was in the area of memory , while other cognitive functions were comparable . However , when the subjects with MCI were compared with the patients with very mild AD , memory performance was similar , but patients with AD were more impaired in other cognitive domains as well . Longitudinal performance demonstrated that the subjects with MCI declined at a rate greater than that of the controls but less rapidly than the patients with mild AD . CONCLUSIONS Patients who meet the criteria for MCI can be differentiated from healthy control subjects and those with very mild AD . They appear to constitute a clinical entity that can be characterized for treatment interventions BACKGROUND Results of previous studies have shown associations between PET imaging of amyloid plaques and amyloid-β pathology measured at autopsy . However , these studies were small and not design ed to prospect ively measure sensitivity or specificity of amyloid PET imaging against a reference st and ard . We therefore prospect ively compared the sensitivity and specificity of amyloid PET imaging with neuropathology at autopsy . METHODS This study was an extension of our previous imaging-to-autopsy study of participants recruited at 22 centres in the USA who had a life expectancy of less than 6 months at enrolment . Participants had autopsy within 2 years of PET imaging with florbetapir ( (18)F ) . For one of the primary analyses , the interpretation of the florbetapir scans ( majority interpretation of five nuclear medicine physicians , who classified each scan as amyloid positive or amyloid negative ) was compared with amyloid pathology ( assessed according to the Consortium to Establish a Registry for Alzheimer 's Disease st and ards , and classed as amyloid positive for moderate or frequent plaques or amyloid negative for no or sparse plaques ) ; correlation of the image analysis results with amyloid burden was tested as a co primary endpoint . Correlation , sensitivity , and specificity analyses were also done in the subset of participants who had autopsy within 1 year of imaging as secondary endpoints . The study is registered with Clinical Trials.gov , number NCT 01447719 ( original study NCT 00857415 ) . FINDINGS We included 59 participants ( aged 47 - 103 years ; cognitive status ranging from normal to advanced dementia ) . The sensitivity and specificity of florbetapir PET imaging for detection of moderate to frequent plaques were 92 % ( 36 of 39 ; 95 % CI 78 - 98 ) and 100 % ( 20 of 20 ; 80 - 100 % ) , respectively , in people who had autopsy within 2 years of PET imaging , and 96 % ( 27 of 28 ; 80 - 100 % ) and 100 % ( 18 of 18 ; 78 - 100 % ) , respectively , for those who had autopsy within 1 year . Amyloid assessed semiquantitatively with florbetapir PET was correlated with the post-mortem amyloid burden in the participants who had an autopsy within 2 years ( Spearman ρ=0·76 ; p<0·0001 ) and within 12 months between imaging and autopsy ( 0·79 ; p<0·0001 ) . INTERPRETATION The results of this study vali date the binary visual reading method approved in the USA for clinical use with florbetapir and suggest that florbetapir could be used to distinguish individuals with no or sparse amyloid plaques from those with moderate to frequent plaques . Additional research is needed to underst and the prognostic implication s of moderate to frequent plaque density . FUNDING Avid Radiopharmaceuticals Objective : To investigate the 10-year risk of dementia in subjects with mild cognitive impairment ( MCI ) ages 40 to 85 years . Methods : We selected subjects from a memory clinic if they met one of the following definitions of MCI : cognitive complaints ( n = 181 ) , aging-associated cognitive decline ( AACD ) ( n = 163 ) , mild functional impairment ( n = 86 ) , or amnestic MCI ( n = 64 ) . Subjects were reassessed after 2 , 5 , and 10 years . The risk of dementia was calculated with Kaplan-Meier statistics . Analyses were conducted in the entire sample and in subgroups of subjects aged 40 to 54 years , 55 to 69 years , and 70 to 85 years . Results : The 10-year risk of dementia was 0.27 ( 95 % CI 0.20 to 0.34 ) in subjects with cognitive complaints , 0.28 ( 95 % CI 0.21 to 0.35 ) in subjects with AACD , 0.44 ( 95 % CI 0.32 to 0.56 ) in subjects with mild functional impairment , and 0.48 ( 95 % CI 0.35 to 0.61 ) in subjects with amnestic MCI . Ninety-one percent of the demented subjects had probable AD . The risk of dementia increased with increasing age for all MCI definitions ( p < 0.001 ) . Depending on the MCI definition used , the risk for dementia ranged from 0 to 0.06 in subjects aged 40 to 54 years , from 0.37 to 0.52 in subjects aged 55 to 69 years , and from 0.77 to 1.0 in subjects aged 70 to 85 years . Conclusions : The majority of subjects with MCI do not progress to dementia at the long term . Age strongly influences the dementia risk . MCI often represents the predementia stage of a neurodegenerative disorder in elderly subjects but rarely in younger subjects CONTEXT Small single-center studies have shown that cerebrospinal fluid ( CSF ) biomarkers may be useful to identify incipient Alzheimer disease ( AD ) in patients with mild cognitive impairment ( MCI ) , but large-scale multicenter studies have not been conducted . OBJECTIVE To determine the diagnostic accuracy of CSF beta-amyloid(1 - 42 ) ( Abeta42 ) , total tau protein ( T-tau ) , and tau phosphorylated at position threonine 181 ( P-tau ) for predicting incipient AD in patients with MCI . DESIGN , SETTING , AND PARTICIPANTS The study had 2 parts : a cross-sectional study involving patients with AD and controls to identify cut points , followed by a prospect i ve cohort study involving patients with MCI , conducted 1990 - 2007 . A total of 750 individuals with MCI , 529 with AD , and 304 controls were recruited by 12 centers in Europe and the United States . Individuals with MCI were followed up for at least 2 years or until symptoms had progressed to clinical dementia . MAIN OUTCOME MEASURES Sensitivity , specificity , positive and negative likelihood ratios ( LRs ) of CSF Abeta42 , T-tau , and P-tau for identifying incipient AD . RESULTS During follow-up , 271 participants with MCI were diagnosed with AD and 59 with other dementias . The Abeta42 assay in particular had considerable intersite variability . Patients who developed AD had lower median Abeta42 ( 356 ; range , 96 - 1075 ng/L ) and higher P-tau ( 81 ; range , 15 - 183 ng/L ) and T-tau ( 582 ; range , 83 - 2174 ng/L ) levels than MCI patients who did not develop AD during follow-up ( 579 ; range , 121 - 1420 ng/L for Abeta42 ; 53 ; range , 15 - 163 ng/L for P-tau ; and 294 ; range , 31 - 2483 ng/L for T-tau , P < .001 ) . The area under the receiver operating characteristic curve was 0.78 ( 95 % confidence interval [ CI ] , 0.75 - 0.82 ) for Abeta42 , 0.76 ( 95 % CI , 0.72 - 0.80 ) for P-tau , and 0.79 ( 95 % CI , 0.76 - 0.83 ) for T-tau . Cut-offs with sensitivity set to 85 % were defined in the AD and control groups and tested in the MCI group , where the combination of Abeta42/P-tau ratio and T-tau identified incipient AD with a sensitivity of 83 % ( 95 % CI , 78%-88 % ) , specificity 72 % ( 95 % CI , 68%-76 % ) , positive LR , 3.0 ( 95 % CI , 2.5 - 3.4 ) , and negative LR , 0.24 ( 95 % CI , 0.21 - 0.28 ) . The positive predictive value was 62 % and the negative predictive value was 88 % . CONCLUSIONS This multicenter study found that CSF Abeta42 , T-tau , and P-tau identify incipient AD with good accuracy , but less accurately than reported from single-center studies . Intersite assay variability highlights a need for st and ardization of analytical techniques and clinical procedures In this article , we describe an image analysis strategy with improved power for tracking longitudinal amyloid-β ( Aβ ) PET changes and evaluating Aβ-modifying treatments . Methods : Our aims were to compare the power of template-based cerebellar , pontine , and cerebral white matter reference regions to track 24-mo florbetapir st and ardized uptake value ( SUV ) ratio ( SUVR ) changes ; to relate those changes to 24-mo clinical declines ; and to evaluate Aβ-modifying treatments in Aβ-positive ( Aβ+ ) and Aβ-negative ( Aβ− ) patients with probable Alzheimer dementia ( pAD ) , in patients with mild cognitive impairment ( MCI ) , in cognitively normal controls ( NCs ) , and in cognitively normal apolipoprotein E4 ( APOE4 ) carriers and noncarriers . We used baseline and follow-up ( ∼24 mo ) florbetapir PET scans from 332 Aβ+ and Aβ− subjects participating in the multicenter Alzheimer ’s Disease Neuroimaging Initiative . Each of the proposed analyses included 31 pAD patients , 187 MCI patients , and 114 NCs . Cerebral-to-white matter , cerebellar , and pontine SUVRs were characterized in terms of their longitudinal variability ; their power to track longitudinal fibrillar Aβ increases in Aβ+ and Aβ− subgroups and cognitively normal APOE4 carriers and noncarriers ; the sample sizes needed to detect attenuated accumulation of or clearance of fibrillar Aβ accumulation in r and omized clinical trials ; and their ability to relate 24-mo fibrillar Aβ increases to clinical declines . Results : As predicted , cerebral-to-white matter SUVR changes were significantly less variable and had significantly greater power to detect 24-mo fibrillar Aβ increases and evaluate Aβ-modifying treatment effects in Aβ+ pAD , MCI , and NC subjects and cognitively normal APOE4 carriers . They were also distinguished by the ability to detect significant associations between 24-mo Aβ increases and clinical declines . Conclusion : A cerebral white matter reference region may improve the power to track longitudinal fibrillar Aβ increases , to characterize their relationship to longitudinal clinical declines , and to evaluate Aβ-modifying treatments in r and omized clinical trials Objective : The objective of this study was to test whether effects of β-amyloid ( Aβ ) pathology on episodic memory were mediated by metabolism and gray matter volume in the early stages of Alzheimer disease . Methods : This was a prospect i ve cohort study . We measured baseline Aβ ( using florbetapir-PET ) , brain function ( using fluorodeoxyglucose-PET ) , and brain structure ( using MRI ) . A mediation analysis was performed to test whether statistical effects of Aβ positivity on cross-sectional and longitudinal episodic memory were mediated by hypometabolism or regional gray matter volume in cognitively healthy controls ( CN , n = 280 ) and mild cognitive impairment ( MCI , n = 463 ) . Results : Lower memory scores were associated with Aβ positivity ( CN , mildly ; MCI , strongly ) , smaller gray matter volumes ( CN , few regions , including hippocampus ; MCI , widespread ) , and hypometabolism . Smaller volumes and hypometabolism mediated effects of Aβ in MCI but not in CN . The strongest individual regions mediated up to approximately 25 % . A combination of brain structure and function mediated up to approximately 40 % . In several regions , gray matter atrophy and hypometabolism predicted episodic memory without being associated ( at p < 0.05 ) with Aβ positivity . Conclusions : Changes in brain structure and function appear to be , in part , downstream events from Aβ pathology , ultimately result ing in episodic memory deficits . However , Aβ pathology is also strongly related to memory deficits through mechanisms that are not quantified by these imaging measurements , and episodic memory decline is partly caused by Alzheimer disease – like brain changes independently of Aβ pathology PURPOSE The compound (E)-4-(2-(6-(2-(2-(2-(18)F-fluoroethoxy)ethoxy)ethoxy ) pyridin-3-yl)vinyl)-N-methylbenzenamine ( [(18)F]AV-45 ) is a novel radiopharmaceutical capable of selectively binding to beta-amyloid ( A beta ) plaques . This pilot study reports the safety , biodistribution , and radiation dosimetry of [(18)F]AV-45 in human subjects . METHODS In vitro autoradiography and fluorescent staining of postmortem brain tissue from patients with Alzheimer 's disease ( AD ) and cognitively healthy subjects were performed to assess the specificity of the tracer . Biodistribution was assessed in three healthy elderly subjects ( mean age : 60.0+/-5.2 years ) who underwent 3-h whole-body positron emission tomography (PET)/computed tomographic ( CT ) scans after a bolus injection of 381.9+/-13.9 MBq of [(18)F]AV-45 . Another six subjects ( three AD patients and three healthy controls , mean age : 67.7+/-13.6 years ) underwent brain PET studies . Source organs were delineated on PET/CT . All subjects underwent magnetic resonance imaging ( MRI ) for obtaining structural information . RESULTS In vitro autoradiography revealed exquisitely high specific binding of [(18)F]AV-45 to postmortem AD brain sections , but not to the control sections . There were no serious adverse events throughout the study period . The peak uptake of the tracer in the brain was 5.12+/-0.41 % of the injected dose . The highest absorbed organ dose was to the gallbladder wall ( 184.7+/-78.6 microGy/MBq , 4.8 h voiding interval ) . The effective dose equivalent and effective dose values for [(18)F]AV-45 were 33.8+/-3.4 microSv/MBq and 19.3+/-1.3 microSv/MBq , respectively . CONCLUSION [(18)F]AV-45 binds specifically to A beta in vitro , and is a safe PET tracer for study ing A beta distribution in human brain . The dosimetry is suitable for clinical and research application A retrospective clinico-pathological study of a consecutive autopsy series of 1050 elderly demented individuals ( mean age 83.4 + /- 6.0 years ; MMSE < 20 ) was performed . Clinical diagnoses were probable or possible Alzheimer disease ( 62.9 % ) , nonspecific degenerative dementia ( 10.4 % ) , vascular dementia ( 10 % ) , Parkinson disease with dementia ( 9.5 % ) , 1.5 % mixed dementia , and 5.7 % other disorders . At autopsy , 86 % revealed Alzheimer-related pathology , but only 42.8 % showed " pure " Alzheimer disease , with additional cerebrovascular lesions in 22.6 % and Lewy body pathology in 10.8 % , while among 660 cases of clinical ly suspected Alzheimer disease , Alzheimer pathology was seen in 93 % , only 44.7 % in " pure " form , and additional vascular lesions and Lewy bodies in 27.7 and 10 % , respectively . The non-Alzheimer cases included Huntington and Creutzfeldt-Jakob disease , frontotemporal dementias , and others . These and other recent data indicate that in patients with the clinical diagnosis of Alzheimer disease its combination with cerebrovascular lesions and Lewy body pathologies is rather frequent . Comparison of clinical and postmortem diagnoses revealed postmortem confirmation of Alzheimer disease in 93 % , of mixed and vascular dementia in 60 and 52.3 % , respectively . 78 % of clinical ly suspected degenerative dementias were pathologically definite Alzheimer disease , while in the clinical Parkinson + dementia group dementia with Lewy bodies accounted for 35 % , Parkinson+Alzheimer disease , and " pure " Alzheimer disease for 29 % , each . A sample of 207 prospect ively studied elderly showed significant negative correlation between the preterminal psychostatus assessed by MMSE and the neuritic Braak stages , with a broad " gray " zone of Alzheimer lesions in mildly to moderately demented subjects . Similar relations between CDR and Braak stages were seen in very old subjects . The present study and the results of other recent series indicate increasing agreement between clinical and autopsy diagnoses in demented aged individuals with variable accuracy rates for different forms of dementia disorders Objective : We hypothesized that florbetapir , a Food and Drug Administration – approved PET tracer , could distinguish cerebral amyloid angiopathy (CAA)–related intracerebral hemorrhage ( ICH ) from hypertensive ICH ( HTN-ICH ) . Methods : We prospect ively enrolled survivors of primary ICH related to probable CAA ( per Boston Criteria , n = 10 ) and HTN-ICH ( n = 9 ) without dementia . All patients underwent florbetapir-PET and multimodal MRI , and patients with CAA had additional Pittsburgh compound B ( PiB ) PET . Amyloid burden was assessed quantitatively ( st and ard uptake value ratio [ SUVR ] ) and visually classified as positive or negative . Results : The CAA and HTN-ICH groups had similar age ( 66.9 vs 67.1 ) , sex , and leukoaraiosis volumes ( 31 vs 30 mL , all p > 0.8 ) . Florbetapir uptake and PiB retention strongly correlated in patients with CAA both globally within cerebral cortex ( r = 0.96 , p < 0.001 ) and regionally in lobar cortices ( all r > 0.8 , all p ≤ 0.01 ) . Mean global cortical florbetapir uptake was substantially higher in CAA than HTN-ICH ( SUVR : 1.41 ± 0.17 vs 1.15 ± 0.08 , p = 0.001 ) , as was mean occipital SUVR ( 1.44 ± 0.12 vs 1.17 ± 0.08 , p < 0.001 ) , even after correcting for global SUVR ( p = 0.03 ) . Visual rating for positive/negative florbetapir demonstrated perfect interrater agreement ( k = 1 ) and was positive for all 10 patients with CAA vs 1 of 9 HTN-ICH patients ( sensitivity 100 % , specificity 89 % ) . Conclusions : Florbetapir appears to label vascular amyloid in patients with CAA-related ICH . The approved florbetapir binary visual reading method can have diagnostic value in appropriate clinical setting s. Classification of evidence : This study provides Class II evidence that florbetapir-PET provides a sensitivity of 100 % ( 95 % confidence interval [ CI ] 66%–100 % ) and specificity of 89 % ( 95 % CI 51%–99 % ) for determination of probable CAA among cognitively normal patients OBJECTIVES To determine the 2-year outcome from 16 different current classifications of mild cognitive impairment ( MCI ) in a population -based sample . DESIGN Prospect i ve cohort study : baseline and 2-year follow-up phases . SETTING Large-scale multicenter study , United Kingdom . PARTICIPANTS : Thirteen thous and four individuals aged 65 and older from the Medical Research Council Cognitive Function and Ageing Study . From this , a sub sample of 2,640 individuals was selected and completed a more-detailed cognitive assessment . Individuals who underwent further assessment were asked to complete annual or 2-year follow-ups . MEASUREMENTS Information on sociodemographic status , general health , cognitive impairment and functional ability were collected using a structured interview . Individuals were classified according to 16 different definitions of MCI . These were applied retrospectively . RESULTS The dominant outcome across definitions was an impairment that was not classifiable or reversion to normality . Progression to dementia was variable and generally poor . Overall progression was highest in classifications in which impairment extended to memory and nonmemory domains . Predictability was age dependent in some but not all classifications . CONCLUSION Current classifications of MCI have variable outcomes in population -based sample s. Progression to dementia is relatively rare and is dependent on age and definition . Selection criteria developed for the clinic are based on a " high risk " approach that leads to exclusion of a large percentage of the impaired population who are neither normal nor demented and for whom no intervention options are currently available . A refined definition of this construct is urgently needed if MCI is to be used to predict dementia in population -based studies Objective : To examine the clinical and biomarker characteristics of patients with amyloid-negative Alzheimer disease ( AD ) and mild cognitive impairment ( MCI ) from the Alzheimer 's Disease Neuroimaging Initiative ( ADNI ) , a prospect i ve cohort study . Methods : We first investigated the reliability of florbetapir− PET in patients with AD and patients with MCI using CSF-Aβ1–42 as a comparison amyloid measurement . We then compared florbetapir− vs florbetapir+ patients with respect to several AD-specific biomarkers , baseline and longitudinal cognitive measurements , and demographic and clinician report data . Results : Florbetapir and CSF-Aβ1–42 + /− status agreed for 98 % of ADs ( 89 % of MCIs ) , indicating that most florbetapir− scans were a reliable representation of amyloid status . Florbetapir− AD ( n = 27/177 ; 15 % ) and MCI ( n = 74/217 , 34 % ) were more likely to be APOE4-negative ( MCI 83 % , AD 96 % ) than their florbetapir+ counterparts ( MCI 30 % , AD 24 % ) . Florbetapir− patients also had less AD-specific hypometabolism , lower CSF p-tau and t-tau , and better longitudinal cognitive performance , and were more likely to be taking medication for depression . In MCI only , florbetapir− participants had less hippocampal atrophy and hypometabolism and lower functional activity question naire scores compared to florbetapir+ participants . Conclusions : Overall , image analysis problems do not appear to be a primary explanation of amyloid negativity . Florbetapir− ADNI patients have a variety of clinical and biomarker features that differ from their florbetapir+ counterparts , suggesting that one or more non-AD etiologies ( which may include vascular disease and depression ) account for their AD-like phenotype To evaluate the performance characteristics of florbetapir F18 positron emission tomography ( PET ) in patients with Alzheimer 's disease ( AD ) , mild cognitive impairment ( MCI ) , and healthy control subjects ( HCs ) Objectives : Florbetapir F 18 PET can image amyloid-β ( Aβ ) aggregates in the brains of living subjects . We prospect ively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline . Methods : A total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment . Subjects included 51 with recently diagnosed mild cognitive impairment ( MCI ) , 69 cognitively normal controls ( CN ) , and 31 with clinical ly diagnosed Alzheimer disease dementia ( AD ) . PET images were visually scored as positive ( Aβ+ ) or negative ( Aβ− ) for pathologic levels of β-amyloid aggregation , blind to diagnostic classification . Cerebral to cerebellar st and ardized uptake value ratios ( SUVr ) were determined from the baseline PET images . Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status . Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline . Results : In both MCI and CN , baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer 's Disease Assessment Scale – Cognitive subscale ( ADAS-Cog ( p < 0.01 ) and Clinical Dementia Rating – sum of boxes ( CDR-SB ) ( p < 0.02 ) . In MCI Aβ+ scans were also associated with greater decline in memory , Digit Symbol Substitution ( DSS ) , and Mini-Mental State Examination ( MMSE ) ( p < 0.05 ) . In MCI , higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog ( p < 0.01 ) , CDR-SB ( p < 0.03 ) , a memory measure , DSS , and MMSE ( p < 0.05 ) . Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ− subjects ( p < 0.10 ) . Conclusions : Florbetapir PET may help identify individuals at increased risk for progressive cognitive decline CONTEXT The ability to identify and quantify brain β-amyloid could increase the accuracy of a clinical diagnosis of Alzheimer disease . OBJECTIVE To determine if florbetapir F 18 positron emission tomographic ( PET ) imaging performed during life accurately predicts the presence of β-amyloid in the brain at autopsy . DESIGN , SETTING , AND PARTICIPANTS Prospect i ve clinical evaluation conducted February 2009 through March 2010 of florbetapir-PET imaging performed on 35 patients from hospice , long-term care , and community health care facilities near the end of their lives ( 6 patients to establish the protocol and 29 to vali date ) compared with immunohistochemistry and silver stain measures of brain β-amyloid after their death used as the reference st and ard . PET images were also obtained in 74 young individuals ( 18 - 50 years ) presumed free of brain amyloid to better underst and the frequency of a false-positive interpretation of a florbetapir-PET image . MAIN OUTCOME MEASURES Correlation of florbetapir-PET image interpretation ( based on the median of 3 nuclear medicine physicians ' ratings ) and semiautomated quantification of cortical retention with postmortem β-amyloid burden , neuritic amyloid plaque density , and neuropathological diagnosis of Alzheimer disease in the first 35 participants autopsied ( out of 152 individuals enrolled in the PET pathological correlation study ) . RESULTS Florbetapir-PET imaging was performed a mean of 99 days ( range , 1 - 377 days ) before death for the 29 individuals in the primary analysis cohort . Fifteen of the 29 individuals ( 51.7 % ) met pathological criteria for Alzheimer disease . Both visual interpretation of the florbetapir-PET images and mean quantitative estimates of cortical uptake were correlated with presence and quantity of β-amyloid pathology at autopsy as measured by immunohistochemistry ( Bonferroni ρ , 0.78 [ 95 % confidence interval , 0.58 - 0.89 ] ; P < .001 ] ) and silver stain neuritic plaque score ( Bonferroni ρ , 0.71 [ 95 % confidence interval , 0.47 - 0.86 ] ; P < .001 ) . Florbetapir-PET images and postmortem results rated as positive or negative for β-amyloid agreed in 96 % of the 29 individuals in the primary analysis cohort . The florbetapir-PET image was rated as amyloid negative in the 74 younger individuals in the nonautopsy cohort . CONCLUSIONS Florbetapir-PET imaging was correlated with the presence and density of β-amyloid . These data provide evidence that a molecular imaging procedure can identify β-amyloid pathology in the brains of individuals during life . Additional studies are required to underst and the appropriate use of florbetapir-PET imaging in the clinical diagnosis of Alzheimer disease and for the prediction of progression to dementia |
12,807 | 31,902,652 | Ultimately , the effects of the aroma-inhalation therapy intervention significantly improved shift-work nurses ' sleep quality .
CONCLUSIONS We established a basic underst and ing of a strategy to measure and improve participants ' sleep quality . | AIM We systematic ally review ed the quality of sleep measurement instruments applied to shift-work nurses and analyzed the effects of intervention research .
BACKGROUND There is a need to test the effects of experimental studies worldwide that conducted interventions to improve the sleep quality of nurses who work shiftwork . | PURPOSE This study aim ed to examine the effects of cognitive behavior therapy for insomnia ( CBT-I ) based on the mobile social networking service ( SNS ) on dysfunctional beliefs and attitudes about sleep , sleep quality , daytime sleepiness , depression , and quality of life among rotating-shift nurses in a hospital in Korea . METHODS A nonequivalent control group pre-post test design was used . The participants included 55 nurses with rotating three-shift work ( 25 in the experimental group and 30 in the control group ) . For the experimental group , CBT-I using mobile SNS was provided once a week for 60 minutes over six weeks . Data were analyzed using descriptive statistics , χ²-test , independent sample s t-test , and Mann-whitney U test with the SPSS 21.0 program . RESULTS In the homogeneity test of the general characteristics and study variables , there were no significant differences between the two groups . Nurses in the experimental group had significantly lower scores on dysfunctional beliefs and attitudes regarding sleep and sleepiness than nurses in the control group . Nurses in the experimental group had significantly higher scores on sleep quality and quality of life than nurses in the control group . CONCLUSION These findings indicate that using the mobile SNS-based CBT-I is feasible and has significant and positive treatment-related effects on rotating-shift nurses ' irrational thoughts and beliefs in association with sleep , sleep quality , daytime sleepiness , and quality of life . These contribute to exp and ing our knowledge of rotating-shift nurses ' sleep issues and their preferences for intervention The purpose of this study was to develop and test the Verran and Snyder-Halpern ( VSH ) Sleep Scale , an instrument to subjectively measure sleep characteristics . Four major sleep factors and their associated characteristics were proposed for the Sleep Scale . Subjects completed three r and omly ordered sleep question naires on three consecutive weekday mornings within the first two hours after arising . Scales included the VSH Sleep Scale , a sleep question naire and a sleep log . The VSH Sleep Scale had a reliability coefficient of .82 ( theta ) . Construct validity was examined by factor analysis and correlations between Sleep Scale items and corresponding items on the two other study instruments . Scale validity also was assessed by the known groups method . Beginning support for the validity of the VSH Sleep Scale is provided 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 This study was an experimental study to compare the inhalation effects of aroma essential oil on the quality of sleep ( QOS ) for shift nurses after working nights . METHODS The participants were 60 healthy adults who did n't have any disease . As an experimental treatment , the participants in the experimental group were asked to inhale essential oil for 3 minutes at a distance of approximately 10 cm fromt heir nose and then they were asked to sleep with the aroma stone beside their head ( within a 30 cm distance ) . QOS were measured four times on Pretest , Day 1 , Day 2 , and Day 3 after they slept . To measure QOS , Perceived QOS ( Numeric Rating Scale ) , the Verran & Synder-Halpern ( VSH ) Sleep Scale were used , and number of awakenings ( NoA ) was measured by Actigraph . RESULTS There were no significant differences in the homogeneity tests for general characteristics and dependent variables prior to the experiments , except for VSH of subjective sleep quality . Also , there was no significant interaction between group and time . The VSH of the experimental group was higher than the control group ( F=6.39 , p=.002 ) . The NoA between the experimental group and the control group was significantly different after experimental treatment 3rd day ( F=13.35 , p=.001 ) . CONCLUSION The findings show that the inhalation of aroma essential oil had effects to increase the quality of sleep . Therefore , the inhalation of aroma essential oil could be applied to general nursing interventions to improve the quality of sleep INTRODUCTION Shift work ( an occupation requiring work between 2200 and 0500H ) comprises approximately 20 % of the workforce in Europe and North America [ 1 ] . This is likely to increase , with many shift workers ( SWs ) in emergency services , retail , hospitality , healthcare , transportation and manufacturing [ 2 ] . SWs are at increased risk for negative health outcomes , including cancer and other chronic diseases [ 3 , 4 ] . Biological changes from poor lifestyle habits related to shift work ( e.g. low physical activity ( PA ) , poor nutrition , obesity ) are thought to contribute to this risk ; these factors are also amenable to lifestyle intervention [ 5 ] . PA in particular , reduces cancer risk [ 6 ] , and has many positive physical and psychological benefits [ 7 ] . It is a simple , cost-effective strategy that may be implemented by individual workers or within workplaces to mitigate risk . Unfortunately , SWs are unlikely to engage in regular PA [ 8 ] . In Canada , only 15.9 % of SWsmeet the PA guidelines and have lower levels of aerobic fitness than those of day workers [ 9 ] . Few behavioural interventions improving health outcomes in SWs have been published [ 10 ] . In a targeted PA intervention , nurses r and omised to 4 months of supervised PA improved aerobic fitness , muscular strength , fatigue and musculoskeletal symptoms . However , authors reported low adherence and large loss to follow-up , perhaps due to the supervised scheduled sessions [ 11 , 12 ] . Sustained behaviour change is a challenge and requires targeted efforts to encourage individuals to reach an adequate dose of PA to change health outcomes [ 13 ] . Due to irregular schedules and time constraints , SWs may be less likely to adhere to a traditional supervised PA intervention with face-to-face behavioural support [ 12 ] . Women SWs cite work schedule interference and lack of time as PA barriers and report scheduling flexibility as the most important in PA [ 14 ] . This highlights the need for a creative and innovative programming to promote PA in SWs . Distance-based interventions , in which individuals exercise independent of study staff or participants , may include telephone counselling and website or smart phone app-based technology . These interventions are highly flexible and may help overcome barriers related to timing and scheduling that are important for SWs . In a review of telephone-based PA interventions , 14 of 17 found evidence for behaviour change [ 15 ] . These may be a way to implement scalable , individuallytailored interventions in SWs . The primary objective of this study was to test the feasibility of a distance-based PA intervention in women SWs . Feasibility studies are important for establishing effective processes and underst and ing re sources required before attempting a r and omised controlled trial ( RCT ) , in order to put forward interventions that are most likely to be efficacious [ 16 ] . As this work was funded by a grant to examine the role of lifestyle in reducing breast cancer risk in SWs , only women were included . A secondary objective was to conduct a preliminary evaluation of intervention efficacy , to estimate effect size for future studies Purpose The Pittsburgh Sleep Quality Index ( PSQI ) is a self-reported question naire that measures sleep quality during the previous month . The aims of this study were to analyze the reliability and validity of the Korean version of the PSQI ( PSQI-K ) and to evaluate its usefulness . Methods We developed the PSQI-K , which involved translating the original PSQI into Korean and then translating back into English to check its accuracy . We tested the validity of the PSQI-K on a total of 394 individuals : 261 with poor sleep ( primary insomnia , n = 211 ; narcolepsy , n = 50 ) and 133 with good sleep . All subjects completed the PSQI-K , 285 had overnight nocturnal polysomnography , and 53 were r and omly selected for a retest with the question naire after 2–4 weeks without any intervening treatment . The mean PSQI-K global scores in each group were analyzed after adjusting for age and sex . Results Cronbach 's α coefficient for internal consistency of the total score of the PSQI-K was 0.84 which shows high reliability . Sensitivity and specificity for distinguishing poor and good sleepers were 0.943 and 0.844 using the best cutoff point of 8.5 . The total and component scores of the PSQI-K for insomnia and narcolepsy were significantly higher than those for controls ( p < 0.05 ) . The test – retest correlation coefficient was 0.65 for the total score ( p < 0.001 ) . There was no significant difference between the two values using the paired t tests . Conclusions The PSQI-K is a reliable and valid question naire for evaluating sleep quality in patients with sleep disorders INTRODUCTION Cancer care workers experience high levels of occupational stress that can have adverse mental and physical health consequences . Educating health professionals about self-care practice s throughout their careers can potentially build resilience . Our study aim ed to evaluate the effects of an educational intervention to improve recovery from job stress , increase satisfaction with current self-care practice s and improve sleep quality . METHODS An equivalent , r and omised comparison , pretest-post-test intervention design was used to investigate the effects of a 1-day workshop ( plus educational material ) compared with written educational material alone , on measures of recovery experiences ( i.e. psychological detachment from work , relaxation , mastery experiences and control over leisure ) , satisfaction with recovery-related self-care practice s and perceived sleep quality of 70 cancer care workers . RESULTS Workshop participants reported greater mean changes 6 weeks post-workshop for total recovery experiences ( F(1,69 ) = 8.145 , P = .008 ) , self-care satisfaction ( F(1,69 ) = 8.277 , P = .005 ) and perceived sleep quality ( F(1,69 ) = 9.611 , P = .003 ) . There was a decline in the scores of the control group over the 6-week period for all measures . Workshop participants not only avoided this decline , but demonstrated increased mean scores , with a significant main effect 6 weeks post-workshop , compared with the control group ( F(3,63 ) = 4.262 , P = .008 ) . CONCLUSIONS A 1-day intervention workshop improved recovery skills , satisfaction with self-care practice s and perceived sleep quality of oncology nurses and radiation therapists . Outcomes were enhanced when participants actively participated in experiential group-based learning compared with receiving written material alone . This intervention has the potential to enhance resilience and prevent burnout at different points in a cancer worker 's career Purpose : Sleep deficit affects neurobehavioral functioning , reduces attention and cognitive function , and negatively impacts occupational safety . This study investigated selective attention levels of nursing staff on different shifts . Methods : Using a prospect i ve , r and omized parallel group study , selective attention was measured using the d2 test in 62 nursing staff in a medical center in Taiwan . Findings : There were significant differences in selective attention indicators ( E% ) between the fixed-day-shift group ( control group ) and rotating-shift group ( experimental group ) : The percentage of errors ( E% ) for night-shift workers in the rotating-shift group was higher than that of fixed-day-shift workers , while the total number of items scanned minus error ( TN − E ) and concentration performance ( CP ) scores were higher for fixed-day-shift workers . Within the experimental group , the error rate on night shift was 0.44 times more than that on day shift and .62 times more than on evening shift ; the TN-E on night shift was 38.99 items less than that on day shift , and the CP was 27.68 items less on night shift than on day shift ; indicating that staff on the night shift demonstrated poorer speed and accuracy on the overall test than did the staff on day shifts . Conclusions : Inadequate sleep and a state of somnolence adversely affected the attention and operation speed of work among night-shift workers . More than 2 days off is suggested when shifting from the night shift to other shifts to provide adequate time for circadian rhythms to adjust The goal of this study is to examine the effects of aromatherapy massage on sleep quality of nurses with monthly rotating night shifts . Subjects were enrolled at a medical center in central Taiwan with overall score ≥ 5 of Pittsburgh Sleep Quality Index ( PSQI ) and r and omly assigned to the treatment or control groups . They were vali date d by pretests during their first graveyard shift in the trial period and the sleep quality information was collected by using the PSQI and sleep detectors . During the second graveyard shift , the treatment group received aromatherapy massage and the control group rested in the same aromatherapy room after work . All subjects filled out the PSQI surveys and the sleep quality information was collected during massage or resting and the following night . We found that the total PSQI was significantly decreased in the treatment group following the aromatherapy massage . Specifically , the components such as subjective sleep quality , sleep disturbance , and daytime dysfunction were significantly decreased . However , there were no significant changes of average PSQI scores between the two groups before and after intervention . Taken together , our study suggested that aromatherapy massage could improve sleep quality of nurses with monthly rotating night shift AIM The aim of this study was to evaluate the effectiveness of improving sleep quality interventions in menopausal women with sleep disturbance . BACKGROUND Sleep disturbances are an extensive and common problem among menopausal women . There is an increased trend in the use of non-pharmacological methods to alleviate sleep disturbances . Studies that have implemented two or more non-pharmacological strategies for menopausal women are scant . METHODS A repeat measurement with a r and omized assignment was conducted . A total of 59 menopausal women with sleep disturbance were recruited and r and omly assigned to experimental ( n = 29 ) and control ( n = 30 ) groups . Participants in the experimental group received four 2-hour improving sleep quality activities , whereas the control group received regular greeting calls . Sleep quality was measured prior to intervention , and on the 5th and 8th weeks by using the Pittsburg 's Sleep Quality Index , and Actiwatch was worn before and during the 8 weeks of intervention . Generalized estimating equation was used to analyze data . RESULTS The results revealed that subjective sleep quality had significant main effect in group and time . The findings of the objective measurement showed that participants in the experimental group had significantly shorter frequency of awakening time and increased sleep efficiency . CONCLUSION The improving sleep quality intervention is a healthy and cost-effective method to improve sleep quality in community-dwelling menopausal women with sleep disturbance The most common problems in hemodialysis patients are sleep disorders and fatigue . This r and omized-controlled experimental study was conducted to determine the effect of aromatherapy applied by inhalation on sleep quality and fatigue level in hemodialysis patients . The study was completed in five hemodialysis centers settled in two provinces with 27 intervention group patients and 35 controls , being totally 62 patients , recruited with simple r and omization . Ethical approval , informed consent from the individuals and institutional permission were obtained . Data were collected with a question naire form and Visual Analogue Scale ( VAS ) for fatigue , Piper fatigue scale , Pittsburgh Sleep Quality Index ( PSQI ) , and follow-up forms for the patient and the research er . Aromatherapy inhalation ( sweet orange and lavender oil ) was performed before going to bed every day for one month to the intervention group patients . No other application has been made to the control group patients except for st and ard hemodialysis treatment . All of the forms were performed at baseline and at follow-up at the end of the four weeks ( baseline and last follow-up ) , VAS and Piper fatigue scale were performed during follow-ups at the end of every week ( the first , second and third follow-ups ) . Data were statistically analyzed with Independent Sample s t-test , one way analysis of variance , Pearson correlation analysis , chi-square test , Friedman and Mann Whitney U tests and Bonferroni test . p<0.05 was set as statistically significant in comparisons . Mean total and sub-dimension scores of VAS , Piper fatigue scale and PSQI ( except for daytime sleepiness dysfunction sub-dimension ) of the intervention and control groups at baseline were not significantly different ( p>0.05 ) . It was found that mean total and sub-dimension scores of VAS , Piper fatigue scale and PSQI of the intervention group significantly decreased in other follow-ups compared to the control group ( p<0.05 ) . Consequently , it was determined that aromatherapy applied by inhalation improved sleep quality , decreased fatigue level and severity in hemodialysis patients . Accordingly , aromatherapy prepared with sweet orange and lavender oil may be recommended to increase sleep quality and to decrease fatigue level of the hemodialysis patients Objective The Epworth sleepiness scale ( ESS ) is widely used to measure the subject 's average sleep propensity across those different situations in daily life , particularly in patients with sleep-disordered breathing . The purpose s of this study were to test the hypothesis that the Korean version of the ESS ( KESS ) is valid and evaluate its usefulness . Material s and methods We developed the KESS , which involved translating into Korean and then translating back into English to check its accuracy . A total of 273 participants ( 181 obstructive sleep apnea (OSA)—37 mild , 61 moderate , 83 severe , 32 simple snoring and 60 normal ) were included in this study . All subjects completed the overnight polysomnograph and 53 of the total subjects were r and omly selected for a retest with the question naire approximately 2∼4 weeks later . The associations between KESS and the degree of OSA were examined through ANCOVA , adjusted for age , sex and BMI . Results The total score and each item 's score of KESS in patients with OSA were significantly higher than subjects with normal controls ( p < 0.01 ) . As the severity of OSA increased , the KESS showed significantly increasing patterns ( p for trend < 0.01 ) . The KESS in patient groups showed good internal consistency ( Cronbach 's α = 0.90 ) and test – retest reliability ( r = 0.78 to 0.93 ) . Conclusion The KESS is a reliable and valid tool for screening patients with daytime sleepiness in Korea The study investigated the number of days off nurses working night shifts need to recover their sleep quality to the level of daytime workers during their days off . This study included 30 day-shift nurses and 32 night-shift nurses . It was conducted as a r and omized clinical trial in the medical and surgical wards of a medical center in northern Taiwan in May and June 2010 using sleep diaries and sleep parameters collected by actigraphy on different workdays and days off . On workdays , the night-shift group had significantly less total sleep time ( TST ) on Day 5 and significantly lower sleep efficiency ( SE ) on Day 3 than the day-shift group . TSTs of the two groups on days off were higher than those on workdays . On the 4th consecutive day off , higher TST , a decrease in WASO , and an increase in SE suggests that the night-shift group had recovered their sleep quality to the level of the day-shift group on their days off . The SE of the night-shift group exceeded that of the day-shift group after the 4th consecutive day off , though the difference was not statistically significant in the present study . Based on these data , it is recommended that night-shift workers arrange a period of at least 4 days off after 5 consecutive night shifts and at least 5 days off if the staff who have previously worked night shifts are being assigned a set of different shifts |
12,808 | 26,018,887 | Published by John Wiley & Sons , Ltd Authors ’ conclusions We found no evidence to support antioxidant supplements for primary or secondary prevention .
Vitamin A , beta-carotene , and vitamin E may increase mortality .
Some observational studies also suggest that antioxidant supplements may prolong life , whereas other observational studies demonstrate neutral or harmful effects .
Overall , the antioxidant supplements did not seem to reduce mortality .
In the analyses of the trials with low risk of bias , beta-carotene , vitamin A , and vitamin E significantly increased mortality .
There were no significant differences between the effects of antioxidant supplements in healthy participants ( primary prevention trials ) or participants with various diseases ( secondary prevention trials ) .
R and omised trials with adequate bias control found no significant effect of vitamin C. In some of our analyses , selenium seems to reduce mortality .
The current evidence does not support the use of antioxidant supplements in the general population or in patients with certain diseases .
The evidence on vitamin C and selenium was not conclusive . | Background Animal and physiological research as well as observational studies suggest that antioxidant supplements may improve survival .
Objectives To assess the effect of antioxidant supplements on mortality in primary or secondary prevention r and omised clinical trials .
P L A I N L A N G U A G E S U M M A R Y No evidence to support antioxidant supplements to prevent mortality in healthy people or patients with various diseases Previous research on animal and physiological models suggest that antioxidant supplements have beneficial effects that may prolong life .
We need evidence from r and omised trials to decide if antioxidant supplements should be used for prevention . | BACKGROUND Results from observational studies suggest that micronutrient status is a determinant of the progression of human immunodeficiency virus ( HIV ) disease . METHODS We enrolled 1078 pregnant women infected with HIV in a double-blind , placebo-controlled trial in Dar es Salaam , Tanzania , to examine the effects of daily supplements of vitamin A ( preformed vitamin A and beta carotene ) , multivitamins ( vitamins B , C , and E ) , or both on progression of HIV disease , using survival models . The median follow-up with respect to survival was 71 months ( interquartile range , 46 to 80 ) . RESULTS Of 271 women who received multivitamins , 67 had progression to World Health Organization ( WHO ) stage 4 disease or died -- the primary outcome --as compared with 83 of 267 women who received placebo ( 24.7 percent vs. 31.1 percent ; relative risk , 0.71 ; 95 percent confidence interval , 0.51 to 0.98 ; P=0.04 ) . This regimen was also associated with reductions in the relative risk of death related to the acquired immunodeficiency syndrome ( 0.73 ; 95 percent confidence interval , 0.51 to 1.04 ; P=0.09 ) , progression to WHO stage 4 ( 0.50 ; 95 percent confidence interval , 0.28 to 0.90 ; P=0.02 ) , or progression to stage 3 or higher ( 0.72 ; 95 percent confidence interval , 0.58 to 0.90 ; P=0.003 ) . Multivitamins also result ed in significantly higher CD4 + and CD8 + cell counts and significantly lower viral loads . The effects of receiving vitamin A alone were smaller and for the most part not significantly different from those produced by placebo . Adding vitamin A to the multivitamin regimen reduced the benefit with regard to some of the end points examined . CONCLUSIONS Multivitamin supplements delay the progression of HIV disease and provide an effective , low-cost means of delaying the initiation of antiretroviral therapy in HIV-infected women BACKGROUND Chronic heart failure ( CHF ) is associated with endothelial dysfunction including impaired endothelium-mediated , flow-dependent dilation ( FDD ) . There is evidence for increased radical formation in CHF , raising the possibility that nitric oxide is inactivated by radicals , thereby impairing endothelial function . To test this hypothesis , we determined the effect of the antioxidant vitamin C on FDD in patients with CHF . METHODS AND RESULTS High-resolution ultrasound and Doppler was used to measure radial artery diameter and blood flow in 15 patients with CHF and 8 healthy volunteers . Vascular effects of vitamin C ( 25 mg/min IA ) and placebo were determined at rest and during reactive hyperemia ( causing endothelium-mediated dilation ) before and after intra-arterial infusion of N-monomethyl-L-arginine ( L-NMMA ) to inhibit endothelial synthesis of nitric oxide . Vitamin C restored FDD in patients with heart failure after acute intra-arterial administration ( 13.2+/-1.7 % versus 8.2+/-1.0 % ; P<.01 ) and after 4 weeks of oral therapy ( 11.9+/-0.9 % versus 8.2+/-1.0 % ; P<.05 ) . In particular , the portion of FDD mediated by nitric oxide ( ie , inhibited by L-NMMA ) was increased after acute as well as after chronic treatment ( CHF baseline : 4.2+/-0.7 % ; acute : 9.1+/-1.3 % ; chronic : 7.3+/-1.2 % ; normal subjects : 8.9+/-0.8 % ; P<.01 ) . CONCLUSIONS Vitamin C improves FDD in patients with CHF as the result of increased availability of nitric oxide . This observation supports the concept that endothelial dysfunction in patients with CHF is , at least in part , due to accelerated degradation of nitric oxide by radicals Primary systemic amyloidosis ( AL ) is a rare disorder characterized by deposition of a monoclonal immunoglobulin light chain or fragment thereof , result ing in dysfunction of the heart , kidney , liver , or nerves . Despite the use of melphalan , prednisone , colchicine , and dimethyl sulfoxide ( DMSO ) , no improvement in median survival has been reported in prospect i ve r and omized studies . We undertook a study of alpha-tocopherol acetate ( vitamin E ) in the treatment of 16 patients with AL because of its reported benefits in animal models of senile and secondary amyloidosis as well as reported benefit in the treatment of secondary amyloidosis in humans . None of the patients showed any objective regression of their disease . The median survival of the entire group was 19.4 months . This survival is not superior to that reported with other agents used in this disease . We conclude that alpha-tocopherol is not a valuable agent in the treatment of AL OBJECTIVES : To identify whether acute lung function effects of ozone can be modulated by antioxidant vitamin supplementation . METHODS : Amateur cyclists ( n = 26 ) were studied in the summer of 1994 in The Netherl and s. Repeated lung function measurements were performed with a rolling seal spirometer after training sessions or competitive races on four to 14 occasions . The cyclists were assigned to two study groups . The supplementation group ( n = 12 ) received antioxidant supplements ( 15 mg beta-carotene , 75 mg vitamin E , and 650 mg vitamin C ) once a day for three months . The control group did not receive supplementation . For each subject , lung function after exercise was regressed on the previous eight hour mean ozone concentration . The individual regression coefficients were pooled for each study group and weighted with the inverse of the variance . RESULTS : The eight hour mean ozone concentration was 101 micrograms/m3 ( 30 to 205 micrograms/m3 ) . For the supplementation group , there was no effect of ozone on FVC , FEV1 , peak expiratory flow ( PEF ) , and maximal mid-expiratory flow ( MMEF ) . For the control group the mean coefficients were negative , except for MMEF . The difference between the groups was 2.08 ( 95 % confidence interval ( 95 % CI ) 1.31 to 2.85 ) ml/microgram/m3 for FVC , 1.66 ( 95 % CI 0.62 to 2.70 ) for FEV1 , 6.83 ( 95 % CI 3.17 to 10.49 ) for PEF , and 0.42 ( 95 % CI -1.38 to 2.22 ) for MMEF . CONCLUSION : The results suggest that antioxidant vitamin supplementation protects against acute effects of ozone on lung function in heavily exercising amateur cyclists Purpose : To evaluate the impact of ascorbic acid of different doses as additional support during luteal phase in infertility treatment by means of a prospect i ve , r and omized , placebo-controlled , group comparative , double-blind study . Methods : Voluntary daily oral intake of either ascorbic acid ( 1 , 5 , or 10 g/day ) or Placebo for 14 days after follicle aspiration for IVF-ET procedure . Data was obtained on 620 cases of women , age < 40 years , undergoing first IVF-embryo transfer cycles in two private out-patient infertility clinics . All women were stimulated by the same protocol . The mean age was 31.73 ( ±4.4 SD ) years . Results : No differences in clinical pregnancy rate and implantation rate were noted in statistical logistic regression analysis between the four intake groups . Conclusions : There was no clinical evidence of any beneficial effect , as defined by main outcome measures , of ascorbic acid on IVF-ET . Our data suggest there is no obvious value of high dosed intake of vitamin C during luteal phase in infertility treatment BACKGROUND Loss of endothelium-derived nitric oxide ( EDNO ) contributes to the clinical expression of coronary artery disease ( CAD ) . Increased oxidative stress has been linked to impaired endothelial vasomotor function in atherosclerosis , and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function . METHODS AND RESULTS In a r and omized , double-blind , placebo-controlled study , we examined the effects of single-dose ( 2 g PO ) and long-term ( 500 mg/d ) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the brachial artery in patients with angiographically established CAD . Flow-mediated dilation was examined by high-resolution vascular ultrasound at baseline , 2 hours after the single dose , and 30 days after long-term treatment in 46 patients with CAD . Flow-mediated dilation improved from 6.6+/-3.5 % to 10.1+/-5.2 % after single-dose treatment , and the effect was sustained after long-term treatment ( 9 . 0+/-3.7 % ) , whereas flow-mediated dilation was 8.6+/-4.7 % at baseline and remained unchanged after single-dose ( 7.8+/-4.4 % ) and long-term ( 7.9+/-4.5 % ) treatment with placebo ( P=0.005 by repeated- measures ANOVA ) . Plasma ascorbic acid concentrations increased from 41.4+/-12 . 9 to 115.9+/-34.2 micromol/L after single-dose treatment and to 95 . 0+/-36.1 micromol/L after long-term treatment ( P<0.001 ) . CONCLUSIONS In patients with CAD , long-term ascorbic acid treatment has a sustained beneficial effect on EDNO action . Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events , this study indicates that ascorbic acid treatment may benefit patients with CAD Carotenoids are useful oral sun protectants , and supplementation with high doses of beta-carotene protects against UV-induced erythema formation . We compared the erythema-protective effect of beta-carotene ( 24 mg/d from an algal source ) to that of 24 mg/d of a carotenoid mix consisting of the three main dietary carotenoids , beta-carotene , lutein and lycopene ( 8 mg/d each ) . In a placebo-controlled , parallel study design , volunteers with skin type II ( n = 12 in each group ) received beta-carotene , the carotenoid mix or placebo for 12 wk . Carotenoid levels in serum and skin ( palm of the h and ) , as well as erythema intensity before and 24 h after irradiation with a solar light simulator were measured at baseline and after 6 and 12 wk of treatment . Serum beta-carotene concentration increased three- to fourfold ( P < 0.001 ) in the beta-carotene group , whereas in the mixed carotenoid group , the serum concentration of each of the three carotenoids increased one- to threefold ( P < 0.001 ) . No changes occurred in the control group . The intake of either beta-carotene or a mixture of carotenoids similarly increased total carotenoids in skin from wk 0 to wk 12 . No changes in total carotenoids in skin occurred in the control group . The intensity of erythema 24 h after irradiation was diminished in both groups that received carotenoids and was significantly lower than baseline after 12 wk of supplementation . Long-term supplementation for 12 wk with 24 mg/d of a carotenoid mix supplying similar amounts of beta-carotene , lutein and lycopene ameliorates UV-induced erythema in humans ; the effect is comparable to daily treatment with 24 mg of beta-carotene alone Nine Type I diabetic patients were r and omized to a double-blind therapeutic trial divided into two study periods of 35 d with either 1 g vitamin E/d or a placebo . Platelet function was estimated at baseline and after treatment from ADP-induced platelet aggregation tests and from generation of oxidative products ( TXB2 , 12 HETE , and malondialdehyde ) after platelet stimulation by 14C arachidonic acid . Platelet function , plasma lipids , and apoproteins were similar before both treatment periods . The vitamin E treatment result ed in 1 ) diminution of platelet aggregation with ADP 2.5 microM ( 56 + /- 4 vs 47 + /- 4 cm2 , p = 0.05 ) and 5 microM ( 70 + /- 5 vs 57 + /- 4 cm2 , p less than 0.01 ) ; 2 ) diminution of malondialdehyde release from platelets ( 6.4 + /- 0.5 vs 5.0 + /- 0.7 nmol/10(9 ) platelets , p less than 0.02 ) ; and 3 ) diminution in the percentage of 14C TXB2 ( 38.1 + /- 2.8 vs 33.3 + /- 3.0 % , p less than 0.05 ) . No significant changes were observed on placebo . Results indicate that high doses of vitamin E diminish ADP-induced platelet aggregation in Type I diabetic patients and suggest that this effect is partly mediated through a diminution of the cyclooxygenase activity BACKGROUND , AIMS , AND PATIENTS : In a prospect i ve follow up and intervention study of colorectal polyps , leaving all polyps less than 10 mm in situ for three years , analysis of redetection rate , growth , and new polyp formation was carried out in 116 patients undergoing annual colonoscopy . The findings in relation to growth and new polyp formation were applied to 58 subjects who received placebo . RESULTS : Redetection rate varied from 75 - 90 % for each year , and was highest in the rectum and sigmoid colon . There was no net change in size of all polyps in the placebo group , however , polyps less than 5 mm showed a tendency to net growth , and polyps 5 - 9 mm a tendency to net regression in size , both for adenomas and hyperplastic polyps . This pattern was verified by computerised image analysis . Patients between 50 and 60 years showed evidence of adenoma size increase compared with the older patients , and the same was true for those with multiple adenomas ( four to five ) compared with those with a single adenoma . The new adenomas were significantly smaller and 71 % were located in the right side of the colon . Patients with multiple adenomas had more new polyps at all the follow up examinations than patients with a single adenoma . One patient developed an invasive colorectal carcinoma , which may be evolved from a previously overlooked polyp . Two polyps , showing intramucosal carcinoma after follow up for three years , were completely removed , as judged by endoscopy and histological examination . CONCLUSIONS : The results show that follow up of unresected colorectal polyps up to 9 mm is safe . The consistency of growth retardation of medium sized polyps suggests extended intervals between the endoscopic follow up examinations , but the increased number of new polyps in the proximal colon indicates total colonoscopy as the examination of choice . The growth retardation of the medium sized polyps may partly explain the discrepancy between the prevalence of polyps and the incidence of colorectal cancer Although there is strong epidemiologic evidence that diets rich in carotenoids such as beta-carotene are associated with a reduced incidence of cancer , the cellular mechanisms underlying this phenomenon remain unknown . This article describes the effect of dietary beta-carotene supplementation on both the expression of functionally associated surface molecules on human monocytes and on the secretion of the cytokine tumor necrosis factor-alpha ( TNF-alpha ) by monocytes , all of which are involved in the initiation and regulation of immune responses involved in tumor surveillance . A double-blind , placebo-controlled , crossover study was undertaken in which 25 healthy , adult male nonsmokers were r and omly assigned to receive beta-carotene ( 15 mg daily ) or placebo for 26 days , followed by the alternative treatment for a further 26 days . The expression of functionally related monocyte surface molecules was quantified by flow cytometry , and ex vivo secretion of TNF-alpha was quantified by an enzyme-linked immunosorbent assay , before and after each treatment period . After dietary supplementation there were significant increases in plasma levels of beta-carotene and in the percentages of monocytes expressing the major histocompatibility complex class II molecule HLA-DR and the adhesion molecules intercellular adhesion molecule-1 and leukocyte function-associated antigen-3 . In addition , the ex vivo TNF-alpha secretion by blood monocytes was significantly increased after supplementation . These findings suggest that moderate increases in the dietary intake of beta-carotene can enhance cell-mediated immune responses within a relatively short period of time , providing a potential mechanism for the anticarcinogenic properties attributed to beta-carotene PURPOSE The dietary trace element selenium has been proposed to be a potential chemopreventive agent for prostate cancer . Epidemiological studies have suggested an inverse association between blood selenium and prostate cancer incidence . However , to our knowledge no study to date has examined selenium absorption by the prostate . Therefore , we determine whether oral selenium supplementation alters selenium levels within the prostate and /or peripheral blood . MATERIAL S AND METHODS In this prospect i ve trial 51 men undergoing transurethral resection of the prostate for benign prostatic hyperplasia were r and omly assigned to serve as controls or receive 200 microg selenium daily orally for 1 month . Sample size was calculated to detect a difference of 30 ng/gm in prostate tissue with a power of 80 % . Peripheral blood was obtained at enrollment and subsequently at surgery , when prostate tissue was also sample d. Selenium levels were determined using inductively coupled plasma mass spectrometry . RESULTS Baseline erythrocyte selenium was within the st and ard reference range . Supplementation increased erythrocyte ( initial median 173 and final median 209 ng/ml , p = 0.008 ) and prostate ( supplement median 241 and control median 196 ng/gm , p = 0.016 ) levels . Erythrocyte levels at surgery correlated poorly with prostate levels in the control ( r = 0.18 ) and supplement ( r = 0.07 ) groups . CONCLUSIONS Oral selenium supplementation increases prostatic and peripheral blood levels in men in a nonselenium deficient population . Blood and prostate levels correlated poorly , suggesting that peripheral blood measurements are a poor indicator of prostatic selenium content The aim of this study was to investigate whether the acute effects of ozone on lung function could be modulated by antioxidant vitamin supplementation in a placebo-controlled study . Lung function was measured in Dutch bicyclists ( n = 38 ) before and after each training session on a number of occasions ( n = 380 ) during the summer of 1996 . The vitamin group ( n = 20 ) received 100 mg of vitamin E and 500 mg of vitamin C daily for 15 weeks . The average ozone concentration during exercise was 77 microg/m3 ( range , 14 - 186 microg/m3 ) . After exclusion of subjects with insufficient compliance from the analysis , a difference in ozone exposure of 100 microg/m3 decreased forced expiratory volume in 1 second ( FEV1 ) 95 ml ( 95 % confidence interval ( CI ) -265 to -53 ) in the placebo group and 1 ml ( 95 % CI -94 to 132 ) in the vitamin group ; for forced vital capacity , the change was -125 ml ( 95 % CI -384 to -36 ) in the placebo group and -42 ml ( 95 % CI -130 to 35 ) in the vitamin group . The differences in ozone effect on lung function between the groups were statistically significant . The results suggest that supplementation with the antioxidant vitamins C and E confers partial protection against the acute effects of ozone on FEV1 and forced vital capacity in cyclists PATIENTS AND METHODS Seventy patients with definitive rheumatoid arthritis were matched to built 2 groups , which were double-blind and r and omized allocated to supplementation with sodium-selenit 200 micrograms/d or placebo for 3 months , each . Both groups were given fish oil fatty acids ( 30 mg/kg body weight ) , DMARDS were continued throughout the study , while variations in steroids or NSAD were admitted . RESULTS Selenium concentrations in erythrocytes of patients with rheumatoid arthritis were 85.1 + /- 26 micrograms/l , and significantly lower than found in an average German population ( 123 + /- 23 micrograms/l ) . During the observation period of 3 months normal selenium concentrations were not restored , despite supplementation higher than RDA . At the end of the experimental period the selenium supplemented group showed less tender or swollen joints , and morning stiffness . Selen-supplemented patients needed less cortisone and NSAD than controls . In accordance with clinical improvement we found a decrease of laboratory indicators of inflammation ( C-reactive protein , alpha 2-globuline , prostagl and in E2 ) . CONCLUSION No side effects of supplementation with selenium were noted , which can be considered as adjuvant therapy in patients with rheumatoid arthritis OBJECTIVE To determine if either supplemental vitamin A , zinc , or both increases cell-mediated immune response in an older population . DESIGN A double-blind , r and omized , controlled trial of supplementation with vitamin A and zinc . SETTING Casa Di Riposo Roma III , a public home for older people in Rome , Italy . SUBJECTS The health and nutritional status of 178 residents were evaluated . One hundred thirty-six residents agreed to participate in the trial and were r and omized into four treatment groups , and 118 of these residents completed the trial . INTERVENTION The four treatments consisted of : ( 1 ) Vitamin A ( 800 micrograms retinol palmitate ) ; ( 2 ) Zinc ( 25 mg as zinc sulfate ) ; ( 3 ) Vitamin A and Zinc ( 800 micrograms retinol palmitate and 25 mg as zinc sulfate ) ; ( 4 ) Placebo capsules containing starch . MAIN OUTCOME MEASUREMENTS Immune tests-counts of leucocytes , lymphocytes , T-cell subsets , and lymphocyte proliferative response to mitogens-were measured before and after supplementation . RESULTS Zinc increased the number of CD4 + DR + T-cells ( P = .016 ) and cytotoxic T-lymphocytes ( P = .005 ) . Subjects treated with vitamin A experienced a reduction in the number of CD3 + T-cells ( P = .012 ) and CD4 + T-cells ( P = .012 ) . CONCLUSIONS These data indicate that zinc supplementation improved cell-mediated immune response , whereas vitamin A had a deleterious effect in this older population . Further research is needed to clarify the clinical significance of these findings Objective : The objective of this study was to determine the effect of individual carotenoid supplementation on biochemical indices of oxidative status in apparently healthy adult males . Methods : The study was a placebo controlled single blind study . Healthy male volunteers ( n=175 ) were assigned to four groups . They received daily supplements of β-carotene ( 15 mg ) , lutein ( 15 mg ) , lycopene ( 15 mg ) and placebo for three months . The effects of the supplementation on antioxidant status were monitored by plasma carotenoid , vitamin C and A levels , glutathione ( GSH and GSSG ) concentrations , protein SH groups , erythrocyte antioxidant enzyme activities ( Cu-Zn SOD , Se-GSH-Px ) and susceptibility of LDL to copper-induced oxidation . Results : β-carotene , lycopene and lutein supplementation led to significant plasma and LDL increases in each of these carotenoids , without modifications of other carotenoid levels in plasma or in LDL . The supplementation failed to enhance the resistance of LDL to oxidation or to modify the LDL polyunsaturated/saturated fatty acid ratio . Vitamin C , GSH , protein SH groups and antioxidant metalloenzyme activities were also unchanged . Conclusion : We did not observe beneficial or adverse effects of lutein , lycopene or β-carotene supplementation on biomarkers of oxidative stress . In apparently healthy subjects , carotenoid supplementation does not lead to significantly measurable improvement in antioxidant defenses 1 . Hypertension affects 30 % of adults and low intakes of antioxidants have been associated with increased risk of hypertension and cardiovascular disease . To investigate the effect of short-term high-dose antioxidant supplementation on blood pressure in hypertensive and normotensive out patients , we undertook a r and omized , double-blind , crossover design placebo-controlled study . 2 . Forty subjects were recruited from medical outpatient clinics , of whom 38 completed the study . Twenty-one were attending for treatment of hypertension and 17 were normotensive , attending for minor gastrointestinal complaints . Subjects were r and omly assigned to receive either 8 weeks placebo followed by 2 weeks washout then 8 weeks antioxidants or vice versa . The combination of antioxidants consisted of 200 mg of zinc sulphate , 500 mg of ascorbic acid , 600 mg of alpha-tocopherol ( sodium succinate salt ) and 30 mg of beta-carotene daily . 3 . Systolic blood pressure fell at the end of the antioxidant phase compared with the placebo phase both in subjects receiving anti-hypertensive therapy ( P < 0.01 ) and those who were normotensive ( P = 0.067 ) . Circulating levels of beta-carotene and alpha-tocopherol increased in all subjects during supplementation ( P < 0.01 ) and urine nitrite increased in hypertensive patients ( P < 0.05 ) . 4 . Short-term oral high-dose combination antioxidant therapy reduces blood pressure , possibly via increased availability of nitric oxide . This study may have implication s for the innovative use of antioxidants as an adjunct to anti-hypertensive therapy CONTEXT Hypersensitivity to electricity is a proposed environmental illness of unknown etiology . Patients report a variety of symptoms that they relate to electric equipment . The afflicted individuals suffer from ill health . Many interventions have been tried but , to date , there is no one specific treatment that has been proven superior to other remedial actions . In general , there is a lack of controlled prospect i ve studies . OBJECTIVE To test the hypothesis that antioxidant therapy reduces symptoms and improves health in patients reporting hypersensitivity to electricity . DESIGN R and omized , double-blind , crossover , placebo-controlled study . SETTING Patients referred to the Environmental Illness Research Centre , Stockholm County Council . PATIENTS Sixteen patients reporting hypersensitivity to electricity . INTERVENTION Antioxidant supplementation ( vitamins C and E , selenium ) . MAIN OUTCOME MEASURES Self-reported symptoms and reported degree of hypersensitivity to electricity , serum levels of uric acid and diphenylpycrylhydrazyl ( DPPH ) . RESULTS The results indicated no significant differences in reported symptoms , reported hypersensitivity to electricity , or oxidative status in serum between periods of antioxidant and placebo treatments . Serum levels of DPPH and uric acid showed no correlation with the reported degree of symptoms or hypersensitivity to electricity . CONCLUSIONS The study did not show any beneficial effect of antioxidant supplementation for patients reporting hypersensitivity to electricity . The results do not support the hypothesis that oxidative stress is a major contributor to ill health in patients who report hypersensitivity to electricity OBJECTIVES The purpose of this study was to test the hypothesis that long-term supplementation with Vitamin E improves endothelium-dependent relaxation in hypercholesterolemia patients and /or chronic smoking , two risk factors that have been shown to be associated with increased radical formation . BACKGROUND Experimental evidence suggests that oxidized low density lipoprotein ( LDL ) impairs endothelium-dependent relaxation , and vitamin E , a lipid-soluble antioxidant , reduces the oxidation of LDL . METHODS Thirteen subjects with hypercholesterolemia , 14 smokers and 15 hypercholesterolemic smokers were enrolled in a double-blind , placebo-controlled study . After baseline measurements of plasma autoantibodies against oxidized LDL and assessment of endothelium-dependent relaxation using intra-arterial forearm infusions of acetylcholine , participants within each group were r and omly assigned in a 1:2 fashion to receive either placebo or vitamin E for 4 months , when plasma levels of autoantibodies against oxidized LDL and vascular function were reassessed . RESULTS Vitamin E significantly augmented endothelium-dependent relaxation in hypercholesterolemic smokers but not in patients with either hypercholesterolemia or chronic smoking . At baseline , hypercholesterolemic smokers had significantly higher autoantibody levels against oxidized LDL ( compared with the other two groups ) , which were significantly reduced after 4 months of vitamin E supplementation . There was a significant relationship between improvement in acetylcholine-induced vasodilation and the change in autoantibody titer against oxidized LDL ( r = -0.59 ; p = 0.002 ) . CONCLUSIONS Long-term vitamin E supplementation improves endothelium-dependent relaxation in forearm resistance vessels of hypercholesterolemic smokers , which are characterized by increased levels of autoantibodies against oxidized LDL . These findings may suggest that the beneficial effect of vitamin E is confined to subjects with increased exposure to oxidized LDL OBJECTIVE The present study was design ed to assess the effect of magnesium plus zinc , vitamins C plus E , and a combination of these micronutrients on nephropathy indexes in type 2 diabetic patients . RESEARCH DESIGN AND METHODS In a r and omized , double-blind , placebo-controlled clinical trial , 69 type 2 diabetic patients were r and omly divided into four groups , each group receiving one of the following daily supplement for 3 months : group M ( n = 16 ) , 200 mg Mg and 30 mg Zn ; group V ( n = 18 ) , 200 mg vitamin C and 100 IU vitamin E ; group MV ( n = 17 ) , minerals plus vitamins ; and group P ( n = 18 ) , placebo . Urinary albumin excretion and N-acetyl-beta-d-glucosaminidase activity ( NAG ) in urine were determined at the beginning and at the end of the trial . Treatment effects were analyzed by general linear modeling . RESULTS Results indicate that after 3 months of supplementation , levels of urinary albumin excretion decreased in the V and MV groups ( P = 0.034 and P = 0.005 , respectively ) . Urinary NAG activity did not significantly change in any treatment groups . Levels of systolic , diastolic , and mean blood pressure significantly decreased in the MV group ( P = 0.008 , P = 0.017 , and P = 0.009 , respectively ) . Also , combination of vitamin and mineral supplementation had significant effects in decreasing fasting serum glucose ( P = 0.035 ) and malondialdehyde concentrations ( P = 0.004 ) and in increasing HDL cholesterol and apolipoprotein A1 levels ( P = 0.019 ) . There was no significant change in the levels of these parameters in the other three groups . CONCLUSIONS In conclusion , the results of the present study provide evidence for the effects of vitamins C and E and also combination of magnesium , zinc , and vitamins C and E supplementation on improvement of glomerular but not tubular renal function in type 2 diabetic patients OBJECTIVE To evaluate the antioxidant and hypocholesterolaemic effects of Terminalia arjuna tree bark ( a popular cardiotonic substance in Indian pharmacopoeia ) and to compare it with a known antioxidant , vitamin E , we performed a r and omized controlled trial . METHODS One hundred and five successive patients with coronary heart disease ( CHD ) presenting to our centre were recruited and using a Latin-square design divided into 3 groups of 35 each . The groups were matched for age , lifestyle and dietary variables , clinical diagnosis and drug treatment status . None of the patients was on lipid-lowering drugs . Supplemental vitamins were stopped for one month before study began and American Heart Association Step II dietary advice was given to all . At baseline , total cholesterol , triglycerides , HDL and LDL cholesterol and lipid peroxide estimated as thiobarbituric acid reactive substances ( TBARS ) were determined . Group I received placebo capsules ; Group II vitamin E capsules 400 units/day ; and Group III received finely pulverized T. arjuna tree bark-powder ( 500 mg ) in capsules daily . Lipids and lipid peroxide levels were determined at 30 days follow-up . RESULTS Response rate in various groups varied from 86 % to 91 % . No significant changes in total , HDL , LDL cholesterol and triglycerides levels were seen in Groups I and II ( paired t-test p > 0.05 ) . In Group III there was a significant decrease in total cholesterol ( -9.7 + /- 12.7 % ) , and LDL cholesterol ( -15.8 + /- 25.6 % ) ( paired t-test p < 0.01 ) . Lipid peroxide levels decreased significantly in both the treatment groups ( p < 0.01 ) . This decrease was more in vitamin E group ( -36.4 + /- 17.7 % ) as compared to the T. arjuna group ( -29.3 + /- 18.9 % ) . CONCLUSIONS Terminalia arjuna tree bark powder has significant antioxidant action that is comparable to vitamin E. In addition , it also has a significant hypocholesterolaemic effect Reactive oxygen species have been implicated in Helicobacter pylori-mediated gastric carcinogenesis , whereas diets high in antioxidant vitamins C and E are protective . We have examined the effect of vitamin C and E supplements in combination with H. pylori eradication on reactive oxygen species activity in H. pylori gastritis . H. pylori-positive patients were r and omized into four groups : triple therapy alone ( Bismuth chelate , tetracycline , and metronidazole for 2 weeks ) , vitamins alone ( 200 mg vitamin C and 50 mg vitamin E , both twice per day for 4 weeks ) , both treatments or neither . Plasma and mucosal ascorbic acid , malondialdehyde and reactive oxygen species were determined before and after treatment . Compared with normal controls ( n 61 ) , H. pylori-positive patients ( n 117 ) had higher mucosal reactive oxygen species and malondialdehyde levels and lower plasma ascorbic acid . Plasma ascorbic acid doubled in both groups of patients receiving vitamins and mucosal levels also increased . Malondialdehyde and reactive oxygen species fell in patients in whom H. pylori was eradicated but vitamin supplements were not effective either alone or in combination with H. pylori eradication . Supplements of vitamins C and E do not significantly reduce mucosal reactive oxygen species damage in H. pylori gastritis PURPOSE This study was design ed to ascertain the effects of a combination antioxidant therapy on plasma protein carbonyls ( PC ) , malondialdehyde ( MDA ) , and whole blood total ( TGSH ) , oxidized ( GSSG ) , and reduced ( GSH ) glutathione in non-resistance trained females after eccentric resistance exercise . METHODS Eighteen women ( aged 19 - 31 yr ) were r and omized in a double-blind manner to either an antioxidant supplement ( N = 9 ; 400 IU vitamin E , 1 g vitamin C , and 90 mug selenium per day ) or a lactose placebo ( N = 9 ) for 14 d before and for 2 d after eccentric elbow flexor exercise . Blood sample s taken before and immediately , 2 , 6 , 24 , and 48 h postexercise were analyzed for PC , MDA , TGSH , and GSSG . RESULTS No treatment by time interaction was noted for any variable , with all blood markers experiencing a change after the exercise in both conditions . Time main effects were observed for PC , MDA , and GSSG , with values elevated above preexercise after the eccentric exercise , whereas GSH concentration decreased after the eccentric exercise . Antioxidant supplementation result ed in a condition main effect for PC and MDA , with lower values compared with placebo . The antioxidant treatment attenuated the rise in both PC ( 75 % ) and MDA ( 100 % ) . CONCLUSION These data suggest that eccentric resistance exercise can increase blood biomarkers of oxidative stress in non-resistance trained females , and this vitamin E , C , and selenium supplementation can attenuate the rise in PC and MDA Free radicals in cigarette smoke ( CS ) cause oxidative damage to proteins , DNA , and lipids , contributing to the pathobiology of atherosclerosis , heart disease , and cancer . In vitro studies have shown that antioxidants quench free radicals and ameliorate certain aspects of biomolecular damage caused by CS . It is hypothesized that a combination of antioxidants is more effective than a single antioxidant , due to their interactions . To investigate whether supplemental antioxidants reduce CS-related lipid peroxidation in vivo and whether they are more effective in combination , we conducted an intervention study in smokers . In a r and omized double-blind placebo-controlled trial , we investigated whether vitamin C or an antioxidant mixture containing vitamin C , alpha-lipoic acid , and vitamin E decreases plasma F(2)-isoprostane levels , an index of oxidant stress , in smokers . Plasma of 126 smokers ( mean age , 46 years ; age range , 20 - 78 years ) was analyzed for F(2)-isoprostanes at baseline and after intervention with antioxidants and placebo . In smokers with a body mass index ( BMI ) above the median , 2 months of daily supplementation with 500 mg of vitamin C decreased plasma F(2)-isoprostane levels by 28.8 pmol/liter when compared with the placebo group ( P = 0.001 ) ; levels in the mixture group were 7.45 pmol/liter lower after treatment , but this difference was not statistically significant ( P = 0.14 ) . There was no treatment effect in smokers with a low BMI . BMI was significantly positively associated with plasma F(2)-isoprostane levels ( trend P = 0.001 ) . Antioxidants decrease smoking-related lipid peroxidation markers of oxidative stress in humans with high BMI . Our results do not indicate that an antioxidant combination is more effective than vitamin C alone . The intake of antioxidants may help prevent smoking-related diseases . Smoking cessation should still be considered the most effective way to prevent smoking-related diseases BACKGROUND There is increasing evidence for the presence of oxidative stress and vitamin C deficiency in dialysis patients . Limited data , however , are available regarding the effects of vitamin C supplementation on oxidative stress and inflammation markers in such patients . METHODS We ran a prospect i ve , r and omized , open-label trial to assess the effects of oral vitamin C supplementation ( 250 mg three times per week ) for 2 months on well-defined oxidative and inflammatory markers in 33 chronic haemodialysis ( HD ) patients . RESULTS Normalization of plasma total vitamin C and ascorbate levels by oral vitamin C supplementation did not modify plasma levels of carbonyls , C-reactive protein and albumin , or erythrocyte concentrations of reduced and oxidized glutathione . CONCLUSION Short-term oral vitamin C supplementation did not modify well-defined oxidative/antioxidative stress and inflammation markers in HD patients . Whether a higher oral dose or the intravenous route can modify these markers remains to be determined We examined the effects of high-dosage vitamin E treatment over a 12-month period on the vascular reactivity of micro- and macrocirculation and left ventricular function in diabetic patients . Subjects ( n = 89 ) were r and omized to vitamin E ( 1,800 IU daily ) or placebo and were followed for 12 months . High-resolution ultrasound images were used to measure the flow-mediated dilation ( FMD ; endothelium dependent ) and nitroglycerin-induced dilation ( NID ; endothelium independent ) of the brachial artery . Laser Doppler perfusion imaging was used to measure vascular reactivity in the forearm skin . Left ventricular function was evaluated using transthoracic echocardiogram . At the end of the 6-month period , a worsening in endothelium-dependent skin vasodilation ( P = 0.02 ) and rise in endothelin levels ( P = 0.01 ) were found in the vitamin E compared with the placebo group . At the end of the 12-month period , a worsening was observed in NID ( P = 0.02 ) and a marginal worsening was seen in systolic blood pressure ( P = 0.04 ) and FMD ( P = 0.04 ) in the vitamin E compared with the placebo group . In addition C-reactive protein levels decreased marginally in the vitamin E compared with the placebo group ( P = 0.05 ) . No changes were observed in left ventricular function . We concluded that long-term treatment with 1,800 IU of vitamin E has no beneficial effects on endothelial or left ventricular function in diabetic patients . Because vitamin E-treated patients had a worsening in some vascular reactivity measurements when compared with control subjects , the use of high dosages of vitamin E can not be recommended OBJECTIVE To explore the association of supplementary and dietary vitamin E and C intake with the progression of coronary artery disease . DESIGN A subgroup analysis of the on-trial antioxidant vitamin intake data base acquired in the Cholesterol Lowering Atherosclerosis Study , a r and omized , placebo-controlled , serial angiographic clinical trial evaluating the risk and benefit of colestipol-niacin on coronary artery disease progression . SETTING Community- and university-based cardiac catheterization laboratories . SUBJECTS A total of 156 men aged 40 to 59 years with previous coronary artery bypass graft surgery . INTERVENTION Supplementary and dietary vitamin E and C intake ( nonr and omized ) in association with cholesterol-lowering diet and either colestipol-niacin or placebo ( r and omized ) . OUTCOME Change per subject in the percentage of vessel diameter obstructed because of stenosis ( % S ) determined by quantitative coronary angiography after 2 years of r and omized therapy on all lesions , mild/moderate lesions ( < 50%S ) , and severe lesions ( > or = 50%S ) . RESULTS Overall , subjects with supplementary vitamin E intake of 100 IU per day or greater demonstrated less coronary artery lesion progression than did subjects with supplementary vitamin E intake less than 100 IU per day for all lesions ( P = .04 ) and for mild/moderate lesions ( P = .01 ) . Within the drug group , benefit of supplementary vitamin E intake was found for all lesions ( P = .02 ) and mild/moderate lesions ( P = .01 ) . Within the placebo group , benefit of supplementary vitamin E intake was not found . No benefit was found for use of supplementary vitamin C exclusively or in conjunction with supplementary vitamin E , use of multivitamins , or increased dietary intake of vitamin E or vitamin C. CONCLUSIONS These results indicate an association between supplementary vitamin E intake and angiographically demonstrated reduction in coronary artery lesion progression . Verification from carefully design ed , r and omized , serial arterial imaging end point trials is needed Objective : We previously reported in an open-label pilot trial that a 24-ingredient multivitamin formula favorably influenced homocysteine concentration and LDL-C oxidation indices following 24 weeks of supplementation . Our current aim was to more thoroughly examine this same formula in a r and omized , placebo-controlled , clinical study . Methods : We examined 182 participants for selected plasma vitamin concentrations and clinical ly relevant variables including homocysteine , lipids and LDL-C oxidation indices at baseline and six months . Results : We found no significant differences between groups for any parameter at baseline . Following six months of vitamin supplementation , we observed elevations in plasma concentrations of vitamin B6 ( as pyridoxal 5′-phosphate ; PLP ) , vitamin B12 , folate , vitamin C , vitamin E and β-carotene ( p < 0.0001 ) , all of which were significantly greater than respective placebo group changes ( p < 0.0001 ) . Homocysteine decreased in the treatment ( 8.38 ± 2.9 vs. 6.93 ± 2.5 μmol/L ; p < 0.0001 ) and placebo group ( 8.17 ± 3.0 vs. 7.42 ± 2.2 μmol/L ; p < 0.0001 ) from baseline to six months , respectively , with reductions in the treatment group being greater than placebo ( p < 0.008 ) . LDL-C oxidation indices were also improved as LDL-C oxidation rate was decreased ( −0.39 μmol/min/g protein ; p < 0.0003 ) and LDL-C lag time increased ( 11.3 min ; p < 0.003 ) in supplemented participants . Further analysis also showed that LDL-C oxidation rate was lower ( p < 0.0007 ) and LDL-C lag time longer ( p < 0.0001 ) for the vitamin group than placebo treatment after six months . Conclusion : We conclude that a multi-ingredient vitamin formula with antioxidant properties has measurable effects on homocysteine and LDL-C oxidation indices OBJECTIVE The role of selenium in preventing cardiovascular diseases has been largely described . Oxidative stress and the subsequent activation of nuclear factor-kappa B ( NF-kappaB ) have been linked to the development of vascular complications . We investigated the effects of selenium supplementation in type 2 diabetic patients on several oxidative stress parameters and NF-kappaB activity . METHODS We enrolled 56 type 2 diabetic patients with similar glycaemic control : 21 were supplemented by selenium ( 960 micro g d(-1 ) , 3 months ) and 27 received a placebo , and 10 nondiabetic subjects formed the control group . To determine NF-kappaB activation , we used an electrophoretic mobility shift assay followed by a semi-quantitative determination of NF-kappaB in peripheral blood mononuclear cells . RESULTS Selenium treatment result ed in a significant increase in plasma selenium and red-cell Se GSH px activity . It had no effect on lipid peroxidation measured by malone-dialdehyde ( MDA ) or on red-cell Cu/Zn SOD . NF-kappaB activity was increased by 80 % in diabetic patients . In patients receiving selenium supplementation , selenium NF-kappaB activity was significantly reduced , reaching the same level as the nondiabetic control group . CONCLUSION In type 2 diabetic patients , activation of NF-kappaB measured in peripheral blood monocytes can be reduced by selenium supplementation , confirming its importance in the prevention of cardiovascular diseases PURPOSE Studies suggest that vitamin E may decrease the risk of prostate cancer . The Prevention Research Veteran Affairs E-vitamin Nutrition Trial is a r and omized , double-blind , placebo controlled study design ed to assess the effects of vitamin E supplementation on biomarkers associated with prostate cancer risk in peripheral blood and prostate tissue . MATERIAL S AND METHODS A total of 44 patients with increased prostate specific antigen ( PSA ) and /or abnormal digital rectal examination on initial evaluation were r and omized to receive 400 IU vitamin E ( 22 ) vs placebo ( 22 ) . Serum vitamin E , PSA , dehydroepi and rosterone , testosterone and insulin-like growth factor-1 ( IGF-1 ) were measured in the 2 groups at baseline and then at 3-month intervals . Results are reported in 28 patients ( placebo in 14 and vitamin E in 14 ) who completed the treatment as specified by the protocol . RESULTS Serum Vitamin E was significantly higher in patients on vitamin E supplementation . alpha-Tocopherol supplementation did not affect the levels of PSA , serum and rogens ( testosterone and dehydroepi and rosterone ) or ( IGF-1 ) . CONCLUSIONS Serum alpha-tocopherol is increased by oral supplementation of vitamin E. We found that alpha-tocopherol supplementation has no effect on serum and rogens , IGF-1 or PSA . The lack of an effect of vitamin supplementation on PSA avoids any bias in the diagnosis of prostate cancer in vitamin E treated patients . Our results suggest that a decrease in prostate cancer risk with alpha-tocopherol is likely to occur through a mechanism that is nonhormonal and independent of IGF-1 Beta-carotene , a quencher of excited species such as singlet oxygen and free radicals , has been reported to protect against cutaneous photodamage , including sunburn acutely and photocarcinogenesis chronically . The present double blind placebo-controlled study examines the effect of beta-carotene supplementation on the human sunburn response and specifically on the induction of sunburn cells at the time of peak reaction intensity ( 24 h ) after a single solar simulated light exposure 3 times the individually determined minimal erythema dose ( MED ) . Administered orally either as a single 120 mg dose to dietarily restricted subjects or for 23 d as a daily 90 mg supplement to subjects on st and ard diets , beta-carotene increased plasma and skin levels of beta-carotene compared to both pretreatment levels and placebo-treated controls , but provided no clinical ly or histologically detectable protection against a 3 MED sunburn reaction . Thus , these data suggest that oral beta-carotene supplementation is unlikely to modify the severity of cutaneous photodamage in normal individuals to a clinical ly meaningful degree OBJECTIVE To examine the effects of vitamin E on total serum protein glycation ( fructosamine ) , hemoglobin glycation ( HbA1c ) , and serum levels of glucose , total cholesterol , triglycerides , LDL-C , HDL-C , apolipoprotein A1 and apolipoprotein B. MATERIAL AND METHODS Sixty poorly controlled diabetic patients were r and omly assigned to receive either 1200 mg/day of vitamin E or identical placebo capsules during a two month period following a double blind cross-over design with a four week wash-out period between regimens . RESULTS Seven patients were excluded from the study because of reasons not related to the medication . In the remaining 53 patients , the levels of serum glucose , fructosamine , HbA1c , total cholesterol , HDL-C , LDL-C , Apo A1 and Apo B did not vary significantly with vitamin E as compared with placebo . CONCLUSIONS No significant effects of vitamin E on any of the parameters evaluated were observed in poorly controlled diabetic patients BACKGROUND Beta-Carotene has been reported to produce regressions in patients with oral leukoplakia , a premalignant lesion . However , previous studies have all been of short duration , with clinical response as the end point . OBJECTIVE To evaluate the duration of response and the need for maintenance therapy in subjects who respond to beta-carotene . METHODS In this multicenter , double-blind , placebo-controlled trial , subjects were given beta-carotene , 60 mg/d , for 6 months . At 6 months , responders were r and omized to continue beta-carotene or placebo therapy for 12 additional months . RESULTS Fifty-four subjects were enrolled in the trial , with 50 being evaluable . At 6 months , 26 subjects ( 52 % ) had a clinical response . Twenty-three of the 26 responders completed the second , r and omized phase . Only 2 ( 18 % ) of 11 in the beta-carotene arm and 2 ( 17 % ) of 12 in the placebo arm relapsed . Baseline biopsies were performed in all patients , with dysplasia being present in 19 ( 38 % ) of the 50 evaluable patients . A second biopsy was obtained at 6 months in 23 subjects who consented to this procedure . There was improvement of at least 1 grade of dysplasia in 9 ( 39 % ) , with no change in 14 ( 61 % ) . Nutritional intake was assessed using food frequency question naires . There was no change in carotenoid intake during the trial . Responders had a lower intake of dietary fiber , fruits , folate , and vitamin E supplements than did nonresponders . Beta-carotene levels were measured in plasma and oral cavity cells . Marked increases occurred during the 6-month induction . However , baseline levels were not restored in subjects taking placebo for 6 to 9 months after discontinuation of beta-carotene therapy . CONCLUSIONS The activity of beta-carotene in patients with oral leukoplakia was confirmed . The responses produced were durable for 1 year Background Epidemiological studies suggest that higher intakes of dietary vitamin C and magnesium may be associated with a reduced risk of asthma Objective : To test the effect of a 21-day supplementation with moderate doses of antioxidant nutrients on biochemical indicators of vitamin , carotenoid and trace element levels in alcohol-dependent patients during a program of alcohol rehabilitation . Design : A r and omized double-blind trial was performed comparing two groups receiving daily either a combination of micronutrients ( beta-carotene : 6 mg , vitamin C : 120 mg , vitamin E : 30 mg , zinc : 20 mg , selenium : 100 μg ) or a placebo . Subjects : 106 alcohol-dependent patients 20 to 60 years of age without severe liver disease , hospitalized for a 21-day rehabilitation program . Measure of Outcome : Vitamin C , retinol , α-tocopherol , zeaxanthin/lutein , β-cryptoxanthin , lycopene , α- and β-carotene , zinc and selenium were measured in serum , initially and after supplementation . Results : ( 1 ) In the placebo group , after 21 days of rehabilitation , serum concentrations of vitamin C and all five carotenoids significantly increased , whereas retinol and α-tocopherol concentrations decreased ; zinc and selenium levels were unaffected . ( 2 ) At the end of the hospital stay , serum indicators were significantly improved in the supplement group as compared to the placebo group for vitamin C , α-tocopherol , β-carotene , zinc and selenium ; conversely , lycopene changes were higher in the placebo group than in supplement group . ( 3 ) Of the serum antioxidants measured at entrance , only vitamin C was significantly depleted in heavy smokers , and , after the supplementation period , vitamin C was efficiently repleted in this later group . Conclusion : Our results indicate that a short-term supplementation with physiological doses of antioxidant vitamins , carotenoids and trace elements during alcohol rehabilitation clearly improves micronutrient status indicators . Heavy smokers in particular seem to respond to vitamin C supplementation Background : Dietary calcium and antioxidants have been suggested as protective agents against colorectal cancer . This has been supported by animal experimental studies , case control and cohort studies . Material s and Methods : In a prospect i ve intervention study of colorectal adenomas , and intermediary stage in colorectal carcinogenesis , 116 polyp-bearing patients received a placebo-controlled daily mixture of β-carotene 15 mg , vitamin C 150 mg , vitamin E 75 mg , selenium 101 µg , and calcium ( 1.6 g daily ) as carbonate for a period of 3 years with annual colonoscopic follow-up to test if the mixture was able to reduce polyp growth or recurrence . All polyps of < 10 mm at enrolment or follow-up were left unresected until the end of the study . Results : 87–91 % of the patients attended the annual endoscopic follow-up investigations , and 19 % of the patients dropped out of the medical intervention . The rest consumed 85 % of the total amount of tablets over the 3 years . The fecal calcium concentration was 2.3–2.7 times higher in patients taking active medication compared to the placebo group . Diet registration showed that , when adding the intake of antioxidants and calcium from diet and intervention , there was a significant difference between the intake of these substances in the active and the placebo group . No difference was detected in the growth of adenomas between the active and the placebo group from year to year and for the total study period . Moreover , there was no effect on polyps of < 5 or 5–9 mm , or on polyps in the different colonic segments analyzed separately . A reduced growth of adenomas was found in patients < 60 years of age taking active medication ( n = 8) compared to those taking placebo ( n = 6 ; mean difference 2.3 mm ; 95 % CI 0.26–4.36 ) . There was a significantly lower number of patients free of new adenomas in the placebo group compared to those taking active medication as tested by logistic regression and Kaplan-Meier analysis ( log-rank test p value 0.035 ) . Subgroup analysis showed that only the group of patients with no family history of colorectal cancer , those with only one adenoma at inclusion , and those < 65 years benefitted from the intervention medication . Conclusion : The study did not find an overall effect on polyp growth . Our data , however , may support a protective role of calcium and antioxidants on new adenoma formation Vitamin C supplementation ( VC ) ( either 500 or 1000 mg/d for 2 wk ) was compared to a placebo treatment ( P ) to ascertain if VC could influence oxidative stress . Twelve healthy males ( 25 + /- 1.4 y ) were r and omly assigned in a counter-balanced design with a 2-wk period between treatments . Data were analyzed using repeated measures ANOVA . Exercise intensity measures ( VO(2 ) , RER , RPE , HR , lactate ) were similar across treatments . Resting blood oxidative-stress markers were unaffected by treatment . Exercise decreased total blood glutathione ( TGSH ) and reduced glutathione ( GSH ) and increased oxidized glutathione ( GSSG ) ( P < 0.01 ) independent of treatment . Protein carbonyls ( PC ) increased 3.8 fold in the P ( P < 0.01 ) . VC attenuated the PC exercise response in a dose-dependent manner ( P < 0.01 ) . Thiobarbituric acid reactive substances ( TBARS ) was not influenced by exercise ( P = 0.68 ) or VC . These data suggest that VC supplementation can attenuate exercise-induced protein oxidation in a dose-dependent manner with no effect on lipid peroxidation and glutathione status The purpose of this investigation was to determine the effects of antioxidant supplementation on DNA damage following exercise . Fourteen subjects were r and omly assigned to one of two groups and required to ingest either antioxidants ( 400 mg alpha-lipoic acid , 200 mg co-enzyme Q10 , 12 mg manganese , 600 mg vitamin C , 800 mg N-acetyl cysteine , 400 microg selenium , and 400 IU alpha-tocopherol per day ) or placebos for 7 d. Exercise increased DNA damage , PS , FRAP , and LDH ( P < 0.05 ) , but not selectively between groups . LDH and PS concentration decreased 1 h post-exercise ( P < 0.05 ) , while LH concentration decreased 1 h post-exercise in the antioxidant group only ( P < 0.05 ) . The antioxidant group had a higher concentration of LH ( P < 0.05 ) , perhaps due to a selective difference between groups post-exercise ( P < 0.05 ) . The main findings of this investigation demonstrate that exhaustive aerobic exercise induces DNA damage , while antioxidant supplementation does not protect against damage AIMS Vascular endothelial dysfunction , an early marker of atherosclerosis , has been demonstrated in Type 2 diabetes mellitus ( DM ) . Vitamin E preserves endothelial function in animal models of diabetes and reduces cardiovascular risk . We examined endothelial function and the effect of vitamin E supplements in uncomplicated Type 2 DM . METHODS Forty-eight subjects with Type 2 DM and 21 controls had endothelial function assessed using forearm venous occlusion plethysmography with endothelium-independent ( sodium nitroprusside ) and dependent ( acetylcholine , bradykinin ) vasodilators . Those with diabetes received 1600 i.u . daily oral alpha-tocopherol or placebo , double-blind for 8 weeks , and had endothelial function reassessed . RESULTS The diabetic group had higher HbA1c ( 6.9+/-1.4 vs 4.8+/-0.6 % ; P<0.01 ) and systolic ( 145+/-15 vs. 130+/-16 mm Hg ; P<0.01 ) but not diastolic blood pressure ( 79+/-8 vs. 76+/-9 mm Hg ; P = 0.15 ) . There was blunted vasodilation to acetylcholine ( 15 microg/min ; P<0.01 ) in subjects with diabetes . Vasodilation to sodium nitroprusside and bradykinin was similar ( all P>0.1 ) . Alpha-tocopherol did not affect vasodilation to nitroprusside ( P>0.1 ) , acetylcholine ( P>0.1 ) or bradykinin ( P>0.1 ) . CONCLUSIONS There may be receptor-specific endothelial dysfunction in subjects with uncomplicated Type 2 DM . This is not improved by treatment with alpha-tocopherol The association between high intake of fruit and vegetables and low incidence of certain cancers is well established . Dietary antioxidants present in these foods are thought to decrease free radical attack on DNA and hence to protect against mutations that cause cancer , but this causal mechanism remains conjectural . We have adopted a molecular epidemiological approach to this question , based on a modified alkaline single-cell gel electrophoresis assay ( " comet assay " ) which specifically detects oxidation of pyrimidines in the DNA of human lymphocytes . In a survey of men 50 - 59 years of age living in the northeast of Scotl and , smokers initially showed significantly more base damage than nonsmokers . Correlations between oxidative base damage and plasma concentrations of various antioxidants were generally negative but not statistically significant . Supplementation of the diet for 20 weeks with vitamin C ( 100 mg/day ) , vitamin E ( 280 mg/day ) , and beta-carotene ( 25 mg/day ) result ed in a highly significant ( P < 0.002 ) decrease in endogenous oxidative base damage in the lymphocyte DNA of both smokers and nonsmokers . In addition , lymphocytes of antioxidant-supplemented subjects showed an increased resistance to oxidative damage when challenged in vitro with H2O2 . These findings strongly support the hypothesis that fruit and vegetables exert a cancer-protective effect via a decrease in oxidative damage to DNA One hundred and sixteen patients were included , during 18 months , in a double-blind placebo-controlled intervention study , with calcium , vitamins A , C , E and selenium ( in a cocktail ) or placebo against growth of colonic polyps . Patients were r and omized within three arms , according to diameter of the largest polyp , < 5 mm , 5–9 mm or > 9 mm . Polyps > 9 mm were resected , the others were left to be measured annually before resection after 3 years . The protocol ( performed in all of the patients ) included registration of demographic data , family and personal history , measurement of polyps , collection of blood specimens , stools and biopsy sample s. Registration of nutritional status , diet history and 5-day prospect i ve food consumption , was performed in 108 patients . The patient compliance was registered every third month by the hospital pharmacist , with concomitant delivery of new boxes of capsules . Additionally , stool collection s were performed from all of the patients for the measurement of faecal calcium , bile salts and fat . Inclusion rate of 37 , 41 and 38 patients in each of the three 6-month periods was uniform . The group with the largest polyps measuring 5–9 mm comprised 44 % of the material . The sex ratio corresponded to that in overall referrals for colonoscopy . The age relationship of size and multiplicity of polyps and the distribution of polyps in the large bowel corresponded to previous experience in polyp-bearing individuals of the same age . In conclusion , the information collected at recruitment of the patients seems to have been adequately registered , giving a reliable and valid data base for comparison during the follow-up of unresected polyps over 3 years OBJECTIVE : Nonalcoholic steatohepatitis ( NASH ) is a common cause of liver disease . Although usually indolent , this disease can progress to cirrhosis in some patients . There is currently no proven medical therapy for the treatment of NASH . The aim of our study was to evaluate the efficacy of combination α-tocopherol ( vitamin E ) and vitamin C in reducing histologic inflammation and fibrosis . METHODS : This was a prospect i ve , double-blind , r and omized , placebo-controlled trial with a total enrollment of 49 patients ; 45 patients completed the study . All patients were r and omized to receive either vitamins E and C ( 1000 IU and 1000 mg , respectively ) or placebo daily for 6 months , based on their initial histologic diagnosis of NASH . Additionally , all patients were given st and ard weight-loss counseling and encouraged to follow a low fat diet ( < 30 fat g/day ) . The pre- and posttreatment liver biopsies were review ed by a single pathologist , who was blinded to the patient 's medication . Biopsies were scored based on a modification of the scoring system published by Brunt et al. ( Am J Gastroenterol 1999;94:2467–74 ) . A score of 0–4 was possible for fibrosis , and a score of 0–6 was possible for inflammation and hepatocyte degeneration and necrosis . In addition , body mass index , glycohemoglobin , lipids , and liver enzymes were followed throughout the study . RESULTS : Forty-five patients completed 6 months of therapy without significant side effects . Vitamin treatment result ed in a statistically significant improvement in fibrosis score ( p = 0.002 ) . No changes were noted in inflammation with treatment . CONCLUSIONS : Vitamin E and vitamin C , in the doses used in this study , were well tolerated and were effective in improving fibrosis scores in NASH patients . No improvement in necroinflammatory activity or ALT was seen with this combination of drug therapy . A larger , multicenter , longer-term trial with vitamin E and vitamin C seems to be warranted Exposure to environmental tobacco smoke ( ETS ) has been linked to increased risk of lung cancer and cardiovascular diseases in nonsmokers . Current research suggests that some of these diseases are associated with elevated oxidative stress . We investigated the effect of antioxidant ( AO ) intervention on the lipid peroxidation biomarker F2-isoprostanes ( F2-IsoPs ) , an index of oxidative stress , in plasma of nonsmokers exposed to ETS ( passive smokers).We measured free F2-IsoP concentrations in plasma of 67 passive smokers at baseline and after 2 mo of daily intervention with AOs or placebo . The study subjects ( 47 females , 20 males ; mean age 46 ± 15 ) were r and omized into one of three treatment groups : vitamin C , " mixture " ( vitamin C , vitamin E , and α-lipoic-acid ) , and placebo . Investigated confounders included plasma baseline AO levels , lipid and total cholesterol profiles , transferrin saturation , and C-reactive protein . Plasma F2IsoP concentrations of subjects in the vitamin C and mixture groups decreased significantly by 17.2 pmol/l ( P = 0.0105 ) and 19.2 pmol/l ( P = 0.0083 ) when compared with the placebo group ( 11.4 % and 12.7 % , respectively ) . Daily AO supplementation ( especially with vitamin C ) decreases this oxidative stress biomarker in passive smokers . This finding might be of importance for the prevention of ETS-associated adverse health effects in nonsmokers Oxidative stress has been recognized as a central feature of smoke induced chronic obstructive pulmonary disease ( COPD ) . Imbalance between oxidant and antioxidant enzymes is also an established fact in these patients . But studies in regard to stable COPD patients and effect of vitamin E supplementation are lacking . Thirty patients with COPD were included in the study . Their baseline clinical examination , spirometry , plasma malondialdehyde ( MDA ) , alpha-tocopherol and red blood cell superoxide dismutase ( SOD ) levels were measured . Twenty healthy non-smokers who were matched for age and sex served as controls . All the above parameters were repeated after 12 weeks of supplementation with 400IU of vitamin E daily . The mean malondialdehyde levels in the patients at baseline were higher than controls ( 5 - 91 ±1.23 nmol/ml vs 4.55 ± 1.51 nmol/ml , P = 0.001 ) , so also was plasma alpha-tocopherol levels ( P<0.00l ) , while SOD levels were lower in the patients compared to controls ( 1692 ± 259 units g/Hb vs 2451 ± 131 units g/Hb , P < 0001 ) . Exogenous vitamin E ( 400 IU per day ) supplementation did not bring about any significant change in plasma alpha-tocopherol and SOD levels . The Pearson ’s co-efficient of correlation between the levels of MDA , vitamin E , SOD ; and spirometric measurements were not significant either on day 1 or after 12 weeks of vitamin E supplementation . The present study shows that initially the plasma lipid peroxide ( MDA ) levels are high and antioxidants ( alpha-tocopherol and SOD ) are low in patients with COPD . Exogenous supplementation with vitamin E does not have any significant effect on the spirometric measurements though it brings down the levels of MDA showing attenuation of further damage . However , inclusion of larger number of patients and supplementation with vitamin E for longer periods may throw more light on free radical injury and protective effects of antioxidants Type II diabetes is characterized by increased oxidative stress , endothelial dysfunction and hypertension . We investigated whether short-term treatment with oral vitamin C reduces oxidative stress and improves endothelial function and blood pressure in subjects with Type II diabetes . Subjects ( n = 35 ) received vitamin C ( 1.5 g daily in three doses ) or matching placebo for 3 weeks in a r and omized , double-blind , parallel-group design . Plasma concentrations of 8-epi-prostagl and in F(2alpha ) ( 8-epi-PGF(2alpha ) ) , a non-enzymically derived oxidation product of arachidonic acid , were used as a marker of oxidative stress . Endothelial function was assessed by measuring forearm blood flow responses to brachial artery infusion of the endothelium-dependent vasodilator acetylcholine ( with nitroprusside as an endothelium-independent control ) and by the pulse wave responses to systemic albuterol ( endothelium-dependent vasodilator ) and glyceryl trinitrate ( endothelium-independent vasodilator ) . Plasma concentrations of vitamin C increased from 58+/-6 to 122+/-10 micromol/l after vitamin C , but 8-epi-PGF(2alpha ) levels ( baseline , 95+/-4 pg/l ; after treatment , 99+/-5 pg/l ) , blood pressure ( baseline , 141+/-5/80+/-2 mmHg ; after treatment , 141+/-5/81+/-3 mmHg ) and endothelial function , as assessed by the systemic vasodilator response to albuterol and by the forearm blood flow response to acetylcholine , were not significantly different from baseline or placebo . Thus treatment with vitamin C ( 1.5 g daily ) for 3 weeks does not significantly improve oxidative stress , blood pressure or endothelial function in patients with Type II diabetes Abstract Objectives : The Physicians ' Health Study ( PHS ) was a r and omized trial of beta-carotene ( 50 mg , alternate days ) and aspirin in primary prevention of cancer and cardiovascular disease among 22,071 US male physicians . This report up date s results for beta-carotene and examines effect modification by baseline characteristics . Methods : Beta-carotene 's effect on cancer over nearly 13 years was examined overall and within subgroups defined by baseline characteristics using proportional-hazards models . Results : 2667 incident cancers were confirmed , with 1117 prostate , 267 colon , and 178 lung cancers . There were no significant differences with supplementation in total ( relative risk ( RR ) = 1.0 , 95 % confidence interval ( CI ) = 0.9–1.0 ) ; prostate ( RR = 1.0 , 95 % CI = 0.9–1.1 ) ; colon ( RR = 0.9 , 95 % CI = 0.7–1.2 ) ; or lung ( RR = 0.9 , 95 % CI = 0.7–1.2 ) cancer , and no differences over time . In subgroup analyses , total cancer was modestly reduced with supplementation among those aged 70 + years ( RR = 0.8 , 95 % CI = 0.7–1.0 ) , daily drinkers of alcohol ( RR = 0.9 , 95 % CI = 0.8–1.0 ) , and those in the highest BMI quartile ( RR = 0.9 , 95 % CI = 0.7–1.0 ) . Prostate cancer was reduced with supplementation among those in the highest BMI quartile ( RR = 0.8 , 95 % CI = 0.6–1.0 ) , and colon cancer was reduced among daily drinkers of alcohol ( RR = 0.5 , 95 % CI = 0.3–0.8 ) . Conclusions : The PHS found no overall effect of beta-carotene on total cancer , or the three most common site-specific cancers . The possibility of risk reduction within specific subgroups remains OBJECTIVE Reductions in serum uric acid levels are clinical ly relevant . Previous studies have suggested a uricosuric effect of vitamin C. Whether vitamin C reduces serum uric acid is unknown . We undertook this study to determine the effects of vitamin C supplementation on serum uric acid concentrations . METHODS The study was a double-blinded placebo-controlled r and omized trial conducted in research units affiliated with an academic institution . Study participants were 184 nonsmokers , r and omized to take either placebo or vitamin C supplements ( 500 mg/day ) for 2 months . RESULTS At the end of the study period , serum uric acid levels were significantly reduced in the vitamin C group ( mean change -0.5 mg/dl [ 95 % confidence interval -0.6 , -0.3 ] ) , but not in the placebo group ( mean change 0.09 mg/dl [ 95 % confidence interval -0.05 , 0.2 ] ) ( P < 0.0001 ) . The same pattern of results was evident in subgroups defined by age , sex , race , body mass index , chronic illness , diuretic use , and quartiles of baseline serum ascorbic acid levels . In the subgroups , from the lowest to the highest quartile of baseline serum uric acid , net mean changes ( 95 % confidence intervals ) in serum uric acid with vitamin C supplementation were -0.4 ( -0.8 , 0.01 ) , -0.5 ( -0.9 , -0.2 ) , -0.5 ( -0.8 , -0.2 ) , and -1.0 ( -1.6 , -0.4 ) mg/dl ( P = 0.06 , 0.005 , 0.003 , and 0.002 , respectively ) . Compared with placebo , vitamin C increased the estimated glomerular filtration rate . CONCLUSION Supplementation with 500 mg/day of vitamin C for 2 months reduces serum uric acid , suggesting that vitamin C might be beneficial in the prevention and management of gout and other urate-related diseases Contracting human skeletal muscle is a major contributor to the exercise-induced increase of plasma interleukin-6 ( IL-6 ) . Although antioxidants have been shown to attenuate the exercise-induced increase of plasma IL-6 , it is unknown whether antioxidants inhibit transcription , translation or translocation of IL-6 within contracting human skeletal muscle . Using a single-blind placebo-controlled design with r and omization , young healthy men received an oral supplementation with either a combination of ascorbic acid ( 500 mg day(-1 ) ) and RRR-alpha-tocopherol ( 400 i.u . day(-1 ) ) ( Treatment , n= 7 ) , or placebo ( Control , n= 7 ) . After 28 days of supplementation , the subjects performed 3 h of dynamic two-legged knee-extensor exercise at 50 % of their individual maximal power output . Muscle biopsies from vastus lateralis were obtained at rest ( 0 h ) , immediately post exercise ( 3 h ) and after 3 h of recovery ( 6 h ) . Leg blood flow was measured using Doppler ultrasonography . Plasma IL-6 concentration was measured in blood sample d from the femoral artery and vein . The net release of IL-6 was calculated using Fick 's principle . Plasma vitamin C and E concentrations were elevated in Treatment compared to Control . Plasma 8-iso-prostagl and in F(2alpha ) , a marker of lipid peroxidation , increased in response to exercise in Control , but not in Treatment . In both Control and Treatment , skeletal muscle IL-6 mRNA and protein levels increased between 0 and 3 h. In contrast , the net release of IL-6 from the leg , which increased during exercise with a peak at 3.5 h in Control , was completely blunted during exercise in Treatment . The arterial plasma IL-6 concentration from 3 to 4 h , when the arterial IL-6 levels peaked in both groups , was approximately 50 % lower in the Treatment group compared to Control ( Treatment versus Control : 7.9 pg ml(-1 ) , 95 % confidence interval ( CI ) 6.0 - 10.7 pg ml(-1 ) , versus 19.7 pg ml(-1 ) , CI 13.8 - 29.4 pg ml(-1 ) , at 3.5 h , P < 0.05 between groups ) . Moreover , plasma interleukin-1 receptor antagonist ( IL-1ra ) , C-reactive protein and cortisol levels all increased after the exercise in Control , but not in Treatment . In conclusion , our results show that supplementation with vitamins C and E attenuated the systemic IL-6 response to exercise primarily via inhibition of the IL-6 protein release from the contracting skeletal muscle per se In areas with severe selenium deficiency there is a higher incidence of thyroiditis due to a decreased activity of selenium-dependent glutathione peroxidase activity within thyroid cells . Selenium-dependent enzymes also have several modifying effects on the immune system . Therefore , even mild selenium deficiency may contribute to the development and maintenance of autoimmune thyroid diseases . We performed a blinded , placebo-controlled , prospect i ve study in female patients ( n = 70 ; mean age , 47.5 + /- 0.7 yr ) with autoimmune thyroiditis and thyroid peroxidase antibodies ( TPOAb ) and /or Tg antibodies ( TgAb ) above 350 IU/ml . The primary end point of the study was the change in TPOAb concentrations . Secondary end points were changes in TgAb , TSH , and free thyroid hormone levels as well as ultrasound pattern of the thyroid and quality of life estimation . Patients were r and omized into 2 age- and antibody (TPOAb)-matched groups ; 36 patients received 200 microg ( 2.53 micromol ) sodium selenite/d , orally , for 3 months , and 34 patients received placebo . All patients were substituted with L-T(4 ) to maintain TSH within the normal range . TPOAb , TgAb , TSH , and free thyroid hormones were determined by commercial assays . The echogenicity of the thyroid was monitored with high resolution ultrasound . The mean TPOAb concentration decreased significantly to 63.6 % ( P = 0.013 ) in the selenium group vs. 88 % ( P = 0.95 ) in the placebo group . A subgroup analysis of those patients with TPOAb greater than 1200 IU/ml revealed a mean 40 % reduction in the selenium-treated patients compared with a 10 % increase in TPOAb in the placebo group . TgAb concentrations were lower in the placebo group at the beginning of the study and significantly further decreased ( P = 0.018 ) , but were unchanged in the selenium group . Nine patients in the selenium-treated group had completely normalized antibody concentrations , in contrast to two patients in the placebo group ( by chi(2 ) test , P = 0.01 ) . Ultrasound of the thyroid showed normalized echogenicity in these patients . The mean TSH , free T(4 ) , and free T(3 ) levels were unchanged in both groups . We conclude that selenium substitution may improve the inflammatory activity in patients with autoimmune thyroiditis , especially in those with high activity . Whether this effect is specific for autoimmune thyroiditis or may also be effective in other endocrine autoimmune diseases has yet to be investigated Hemodialysis deteriorates oxidative stress . Vitamin E is an antioxidant whose regeneration is provided for by vitamin C. The authors tested the effects of a vitamin E-modified membrane ( E ) , nonmodified cellulose membrane ( O ) , and vitamin C infusion ( 500 mg , C ) into the arterial blood line during dialysis on parameters of oxidative stress . In a short-term study , 24 patients were subjected to a single dialysis session with E , O , E with C , and O with C protocol s. In a long-term study ( 12 weeks ) , 20 patients were r and omized into groups with C and without C on each dialysis , and both groups had dialysis using O , E , and again O membrane for 4 weeks each . In the short-term study , thiobarbituric acid reacting substances ( TBARS ) in plasma rose after dialysis ( p < 0.02 ) with O , and no changes were observed in the other 3 protocol s. In the long-term study , predialysis TBARS declined when using E both in the groups with C ( p < 0.02 ) and without C ( p < 0.05 ) . A switch over to O result ed in TBARS returning to baseline levels . The E membrane prevented an increase in lipid peroxidation during single dialysis , and long-term use of the E membrane also result ed in a decrease in the predialysis lipid peroxidation level . The antioxidant capacity of the E membrane was not enhanced by vitamin C infusion . High doses of vitamin C administered during dialysis using a nonmodified cellulose membrane prevented an increase in lipid peroxidation , most probably due to the enhanced rate of endogenous vitamin E regeneration Background : One of the suggested mechanisms of increased cardiovascular risk in postmenopause is a loss of the antioxidant effects of estrogens . It has been shown that classical cardiovascular risk factors increase oxidative stress on the arterial wall , and that endothelial cells react to this insult by increased expression of cellular adhesion molecules ( CAM ) , which in turn are markers of arterial wall inflammation . Methods : A r and omized , placebo-controlled , double-blind study was performed in 60 postmenopausal women with high cardiovascular risk profiles , but free from clinical atherosclerotic disease . Patients were r and omized to either antioxidant supplementation ( using a combination of natural antioxidants ; n = 30 ) or placebo ( n = 30 ) , and followed for 12 weeks . The concentrations of the adhesion molecules sVCAM-1 and sICAM-1 were measured by ELISA at baseline and at the end of the study , as well as total cholesterol , LDL , HDL , triglycerides and blood pressure . Results : 27 women in the antioxidant supplementation group and 29 on placebo completed the study . At baseline , there were no significant differences in measured parameters between the groups : sICAM-1 concentrations were 341.8 ± 116.9 vs. 349.9 ± 104.6 ng/ml ( active treatment vs. placebo ; p = n.s . ) and sVCAM-1 concentrations were 780.5 ± 325.8 vs. 761.0 ± 333.7 ng/ml ( p = n.s . ) . In contrast , at the end of the study , sICAM-1 concentrations were 301.6 ± 56.0 vs. 356.0 ± 134.8 ng/ml ( active treatment vs. placebo ; p = 0.053 ) and sVCAM-1 concentrations were 656.0 ± 326.5 vs. 818.5 ± 381.0 ng/ml ( p = 0.04 ) . There were no significant differences between or changes within the groups in measured cholesterol and blood pressure . Conclusion : Antioxidant supplementation reduces serum concentrations of endothelium-derived adhesion molecules sICAM-1 and sVCAM-1 in postmenopausal women with high cardiovascular risk profiles The number of bleomycin-induced chromosomal breaks in cultured peripheral blood lymphocytes has been proposed as a measure of the sensitivity of an individual to carcinogens . Although " mutagen sensitivity " ( clastogenicity ) may be a useful biomarker for the identification of individuals at high risk for DNA damage , there is some uncertainty whether the results of this assay can be modified by environmental factors , such as diet . We design ed an intervention study to determine whether micronutrient supplementation with beta-carotene and alpha-tocopherol influenced the mutagenicity score among 22 healthy volunteers . This intervention study followed a double-blind , r and omized , cross-over design . Chromatid breaks ranged from 0.30 to 2.30 per cell and were uncorrelated with plasma beta-carotene ( r = -0.07 ; P = 0.50 ) and a-tocopherol ( r = -0.01 ; P = 0.92 ) levels , after accounting for the time of the measurement . The average number of breaks per cell was similar ( P for difference in means = 0.90 ) among subjects during periods of vitamin supplementation ( mean = 0.87 breaks per cell ) and placebo ( mean = 0.86 breaks per cell ) , averaged over groups and after adjustment for baseline breaks . Substantial within-person variation may indicate some imprecision in the mutagen sensitivity assessment . Our results suggest that mutagen sensitivity is not affected by plasma levels of beta-carotene or alpha-tocopherol . Although mutagen sensitivity does not appear to be modified by changes in plasma levels of two common antioxidant vitamins , it may be useful for the identification of high-risk individuals for participation in large intervention studies with cancer outcomes Rationale Several investigators implicated role of free radical-mediated pathology in schizophrenia . No study has ever examined the effect of vitamin C with atypical antipsychotics in the treatment of schizophrenia . Objective The aim of this study was to examine the effect of oral vitamin C with atypical antipsychotics on serum malondialdehyde ( MDA ) , plasma ascorbic acid levels , and brief psychiatric rating scale ( BPRS ) score in schizophrenic patients . Method Forty schizophrenic patients participated in a prospect i ve , double-blind , placebo-controlled , noncrossover , 8-week study . The patients with schizophrenia were divided r and omly into placebo and vitamin C group of 20 each . Serum MDA and plasma ascorbic acid were estimated by methods of Nischal and Aye , respectively . Result Increased serum MDA and decreased plasma ascorbic acid levels were found in schizophrenic patients . These levels were reversed significantly after treatment with vitamin C along with atypical antipsychotics compared to placebo with atypical antipsychotics . BPRS change scores at 8 weeks improved statistically significant with vitamin C as compared to placebo . Conclusion Oral supplementation of vitamin C with atypical antipsychotic reverses ascorbic acid levels , reduces oxidative stress , and improves BPRS score , hence both the drugs in combination can be used in the treatment of schizophrenia Objective : To assess the effects of supplementation with the carotenoids , β-carotene or lycopene , at levels achievable within a diet rich in fruit and vegetables , on immune function in a group of free-living healthy elderly . Design : A double-blind r and omized placebo-controlled trial . T cell subsets and the expression of functionally associated cell surface molecules , quantified by flow cytometry , and lectin-stimulated lymphocyte proliferation , were compared before and following the treatment period . Subjects : Fifty-eight subjects aged over 65 y were recruited ; 52 were included in the final analysis . Interventions : Participants received one placebo , one lycopene ( 13.3 mg ) or one β-carotene ( 8.2 mg ) capsule daily for 12 weeks . Results : No significant differences were observed in any of the parameters examined following either lycopene or β-carotene supplementation . Conclusions : In well-nourished , free-living , healthy elderly individuals , supplementation with relatively low levels of β-carotene or lycopene is not associated with either a beneficial or detrimental effects on several aspects of cell-mediated immunity . Sponsorship : Financial support was provided by the Commission of the European Communities , specific programme AIR2 CT93 - 0888 DGXII SSMA , ‘ Increased fruit and vegetable consumption within the EC : potential health benefits ’ , co-ordinated by Professor S Southon , Institute of Food Research , Norwich , UK.European Journal Clinical Nutrition ( 2001 ) 55 , 1 . The antioxidant properties of vitamin E ( alpha-tocopherol ) have been proposed to account for a possible protective effect in coronary artery disease . Coronary risk factors are associated with depressed endothelium-derived nitric oxide responses , and some evidence suggests increased quenching of the vasodilator effect of nitric oxide by oxygen free radicals . This study examined the possibility that vitamin E supplementation would improve basal function of the nitric oxide dilator system in long-term smokers and non-smokers . 2 . Nine healthy male life-long non-smoking subjects and eight smokers ( 36 + /- 6 cigarettes per day , > 7 years ) were given 1000 i.u . of vitamin E per day for a 4-week period , while five additional non-smokers received placebo . Forearm blood flow responses to intra-arterial infusion of noradrenaline ( 60 , 120 and 240 rho mol/min ) and the competitive inhibitor of nitric oxide synthesis , NG-monomethyl-L-arginine ( 1 , 2 and 4 mumol/min ) were measured before and after therapy . 3 . No changes were evident in the constrictor responses to noradrenaline or NG-monomethyl-L-arginine in any group . These results indicate that vitamin E supplementation does not influence basal activity of the nitric oxide-dilator system in vivo OBJECTIVE Vitamin E , the most potent naturally occurring lipid soluble antioxidant has been suggested to possess both anti-inflammatory and analgesic activity in humans . This double blind and r and omised study used a broad spectrum of clinical and laboratory parameters to investigate whether there was any additional anti-inflammatory or analgesic effects , or both , of orally administered α-tocopherol in rheumatoid arthritis patients who were already receiving anti-rheumatic drugs . METHODS Forty two patients were enrolled and treated with α-tocopherol ( n=20 ) at a dose of 600 mg twice a day ( 2 × 2 capsules ) or with placebo ( n=22 ) for 12 weeks . The following parameters were measured : ( 1 ) Three clinical indices of inflammation — the Ritchie articular index , the duration of morning stiffness , and the number of swollen joints ; ( 2 ) three measures of pain — pain in the morning , pain in the evening , and pain after chosen activity ; ( 3 ) haematological and biochemical measures of inflammatory activity ; ( 4 ) assays for the oxidative modification of proteins and lipids . RESULTS All laboratory measures of inflammatory activity and oxidative modification were unchanged . Furthermore , the clinical indices of inflammation were not influenced by the treatment . However , the pain parameters were significantly decreased after vitamin E treatment when compared with placebo . CONCLUSION The results provide preliminary evidence that vitamin E may exert a small but significant analgesic activity independent of a peripheral anti-inflammatory effect , but which complements st and ard anti-inflammatory treatment OBJECTIVE To evaluate the effects of a combination of micronutrient antioxidants ( selenium , beta-carotene , vitamin C , vitamin E and methionine ) with allopurinol in patients with limited cutaneous systemic sclerosis ( SSc ) . METHODS The study was design ed as a placebo-controlled double-blind crossover study . A carryover effect was detected retrospectively for some of the prescribed antioxidants , and so the data were analysed as : ( a ) a between group comparison of the first 10 week treatment period ; and ( b ) a within group comparison of the first and second 10-week periods in those who received placebo treatment first . Study end-points were plasma von Willebr and factor ( vWF ) , thermographic response to a st and ard cold challenge , frequency and duration of Raynaud 's attacks , patient opinion , and specialised biochemical parameters ( fatty acid profiles , antioxidants and markers of free radical injury ) . RESULTS Thirty-three patients were recruited . The median duration of Raynaud 's phenomenon was 10 years ( range 2 to 50 years ) in the active-first group and 10 years ( range 4 to 53 years ) in the placebo-first group . In the 10-week study , there were no differences between the active and placebo groups in the change from baseline for vWF , for the parameters of the rewarming curve , or for patients ' symptoms . Despite a rise in circulating antioxidant levels , there was no fall in markers of free radical mediated injury . In the 20-week cross-over study , patients did not experience any clinical benefit from active treatment compared to placebo . CONCLUSION No clinical benefit could be demonstrated from active treatment . There are several possible explanations for this negative result , including the short duration of therapy . It is possible that antioxidant therapy , to be effective , needs to be given early in the SSc disease process , before the onset of irreversible tissue damage OBJECTIVE Vitamin E ( alpha-tocopherol ) , a free-radical scavenger , has been reported to improve symptoms of tardive dyskinesia . The authors attempted to replicate this finding under more controlled conditions in a larger study group . METHOD Fifteen in patients and six out patients with tardive dyskinesia received up to 1600 IU/day of vitamin E for 6 weeks in a double-blind , placebo-controlled crossover study . Abnormal Involuntary Movement Scale ( AIMS ) examinations of these patients were videotaped and rated independently by two trained raters . Levels of neuroleptic medication and vitamin E were measured during both treatment periods . Eighteen patients who demonstrated high blood levels of vitamin E were included in the data analysis . RESULTS Vitamin E levels were significantly higher while the patients were receiving vitamin E than while they were receiving placebo . For all 18 patients , there were no significant differences between AIMS scores after receiving vitamin E and AIMS scores after receiving placebo . In agreement with previous studies , however , the nine patients who had had tardive dyskinesia for 5 years or less had significantly lower AIMS scores after receiving vitamin E than after receiving placebo . There were no changes in neuroleptic levels during vitamin E treatment . CONCLUSIONS Vitamin E had a minor beneficial effect on tardive dyskinesia ratings in a selected group of patients who had had tardive dyskinesia for 5 years or less . This effect was not due to an increase in blood levels of neuroleptic medications Eleven patients with tardive dyskinesia were treated in a double-blind study of vitamin E or placebo for 12 weeks . Abnormal Involuntary Movement Scale ( AIMS ) ratings were performed before and after treatment . Patients receiving vitamin E showed a significant reduction in their AIMS scale score , but patients receiving placebo showed no significant change . Vitamin E had a helpful effect even for patients whose tardive dyskinesia was mild and long-term OBJECTIVES The objective of this study was to examine the effects of treatment with atorvastatin , alpha-tocopherol and the combination of both , on lipoproteins and oxidative stress in dialysis patients . DESIGN AND SETTING This double-blind r and omised placebo-controlled trial was performed at the dialysis department of a non-university hospital . SUBJECTS , INTERVENTION AND MEASUREMENTS : A total of 44 clinical ly stable , non-diabetic patients on dialysis therapy ( 23 on haemo- and 21 on peritoneal-dialysis ) without manifest cardiovascular disease were included in this study . They were r and omised for treatment during a period of 12 weeks with 40 mg atorvastatin + placebo alpha-tocopherol ( group 1 ) once daily , 800 IU alpha-tocopherol + placebo atorvastatin once daily ( group 2 ) , 40 mg atorvastatin + 800 IU alpha-tocopherol once daily ( group 3 ) , or placebo atorvastatin + placebo alpha-tocopherol once daily ( group 4 ) . Assessment of lipid profile and oxidative stress was performed at the start of the study and after 12 weeks of treatment . RESULTS Treatment with atorvastatin reduced total cholesterol , triglycerides ( TG ) , low-density lipoprotein ( LDL ) cholesterol , apolipoprotein B ( apoB ) and levels of oxidised LDL ( oxLDL ) with 30 - 43 % . It had no influence on LDL oxidisability . Additional supplementation with alpha-tocopherol had no effect on lipid profile and oxLDL levels but decreased in vitro LDL oxidisability . No side-effects were observed . CONCLUSIONS Treatment with atorvastatin is effective in lowering plasma total cholesterol , TG , LDL , apoB and oxLDL in a population of stable dialysis patients and might therefore be an effective tool in improving the poor cardiovascular outcome in these patients . Supplementation of alpha-tocopherol to atorvastatin had beneficial effects on in vitro LDL oxidisability and might therefore be of additional value . Further research on the clinical effects of treatment with atorvastatin in combination with alpha-tocopherol is necessary A combination of celecoxib and selenium was used in a r and omized double-blind Phase II trial as a preliminary study to a multicenter Phase III colorectal cancer chemoprevention trial using these two agents together . The purpose of this trial was to determine whether high-selenium baker ’s yeast [ ( Saccharomyces cerevisiae ) 200 μg once daily ] in combination with celecoxib ( 400 mg once daily ) altered the steady-state plasma concentration of celecoxib or produced clinical ly significant toxicities . Seventy-three healthy subjects ( ages 40–75 years ) were recruited to the 6-week study from the general local population and were r and omized to either the celecoxib plus selenized baker ’s yeast group or the celecoxib plus placebo group after a 2-week run in period of celecoxib only . Blood sample s were taken at baseline ( to document that there was no evidence of celecoxib intake ) , after the 2-week run-in period on celecoxib to verify steady-state blood levels of this agent , and at end of study ( 4 weeks postr and omization ) . Toxicities were monitored at 2 weeks after initiation of celecoxib , at 4 weeks after initiation , and at the end of the study . Blood level concentrations of celecoxib did not differ between the two groups as determined by high-performance liquid chromatography analysis nor were there significant differences in blood chemistry values between the two groups . Subjects ’ self-report of general physical toxicities was uncommon and limited to National Cancer Institute toxicity grade 2 or less ; however , 2 female participants ( 3 % ) were removed from the study medications because of grade 2 edema and significant weight gain after 2 and 2.5 weeks of celecoxib administration . In conclusion , high-selenium yeast and celecoxib can be taken at the described doses with minimum short-term negative effects . In future Phase III chemoprevention trials of celecoxib , weight gain should be carefully monitored , and participants should be made aware of this potential side effect before study entry OBJECTIVES The aims of this study were to determine if ultraviolet light ( UV ) is immunosuppressive in healthy older males , if beta-carotene ( betaC ) supplementation could prevent any observed UV-induced immunosuppression , and to compare these effects with those observed previously in younger men . METHODS The study was a placebo-controlled , r and omized trial that employed a 2 x 2 factorial design . Healthy older men ( mean age 65.5 years ) received 30 mg betaC or placebo daily throughout the 47-day trial , while on a low carotenoid diet . After 28 days , half of each group received 12 suberythemic exposures to UV over a 16-day period . Delayed-type hypersensitivity ( DTH ) tests and plasma carotenoid assays were performed at baseline , pre-UV and post-UV time points , with DTH testing performed on an area of skin protected from UV exposure . RESULTS UV exposure result ed in significantly suppressed DTH response in the placebo group but not in the betaC-UV group . While there was no significant interaction between betaC supplementation and UV on DTH response , there was a significant inverse relationship between final plasma betaC concentration and extent of UV-induced suppression of DTH response . A similar correlation existed among subjects not exposed to UV . CONCLUSIONS Suberythemic UV exposure was immunosuppressive , as measured by DTH response , in healthy older men as in younger men . Higher plasma betaC was significantly associated with maintenance of DTH response , although the extent of protective effect of betaC appeared less than previously observed in younger subjects . The attenuated effect of betaC in the older UV-exposed subjects may have result ed in part from muted plasma betaC responses to betaC supplementation and /or higher plasma vitamin E levels than those of younger men . The finding that stronger DTH responses were associated with higher plasma betaC concentrations in both UV and non-UV subjects further supports a role for this nutrient in immunomodulation Endogenous antioxidants are decreased in skin and blood during UV exposure . Combined supplementation of β-carotene , α-tocopherol and ascorbic acid in addition to topical sunscreens may help to lower the risk of sunburning . Acute UV erythema with sunburn reaction are the most important factors in conjunction with the cumulative life-long UV dose for inducing skin damage result ing in photoageing and precancerous and cancerous lesions . Therefore , a clinical , r and omized , double-blind , parallel group , placebo-controlled study was conducted in healthy young female volunteers ( skin type II ) investigating the preventive , photoprotective effect of supplementation with Seresis ® , an antioxidative combination containing both lipid and water-soluble compounds : carotenoids ( β-carotene and lycopene ) , vitamins C and E , selenium and proanthocyanidins . In this study , the oral administration of Seresis appeared to be well tolerated . The preparation contains antioxidant compounds in quantities occurring at physiological levels and can therefore be used safely over a long period of time . Despite the fact that the assessment of the light sensitivity ( minimal erythemal dose , chromametry ) of the skin did not show any statistically significant differences between the Seresis and the placebo group , a clear statistical trend , however , could be demonstrated , i.e. Seresis was able to slow down the time of the development and grade of UVB-induced erythema . The primary efficacy parameter matrix metalloproteinases 1 ( MMP-1 ) between treatment and placebo group following UV irradiation showed a significant difference ( p < 0.05 ) , which occurred due to the fact that after a 2-week UV irradiation , MMP-1 slightly increased ( p < 0.03 ) in the placebo group and decreased ( p < 0.044 ) in the treated group . The MMP-9 changes showed a clear tendency of decrease in the Seresis group ( p < 1.393 ) and increase ( p < 0.048 ) in the placebo group . These data emphasise that supplementation with Seresis decreases the UV-induced expression of MMP-1 and 9 , which might be important in photoprotective processes . From our data , we thus finally draw the conclusion that by the combination of antioxidants , such as in the formulation of Seresis , a selective protection of the skin against irradiation can be achieved . This might be important for future recommendations for immediate suppression of the early phase of UV-induced erythema , that means pharmacological prevention of sunburn reaction as well as subsequent chronic skin damage We report here the results of a double-blind , r and omized trial of the effect of vitamin E on clinical ly palpable benign breast findings . Seventy-three women who attended a breast screening clinic were assigned r and omly to either a daily regimen of 600 IU vitamin E ( n = 37 ) or a placebo ( n = 36 ) . At the initial visit sociomedical information was obtained for each patient and breast examination performed , with a score ranging from 0 to 4 recorded for each quadrant of both breasts . Thirty-two women in the vitamin E group and 30 in the placebo group returned for follow-up breast examination approximately 2 months later . Scores for mean ages and breast findings at entry were similar for women in the two groups . We found no differences between the vitamin E and placebo groups in scores for changes in breast findings at the end of the study period and no differences in the proportion of women who reported feeling less premenstrual pain ( 40.0 % and 41.4 % , respectively ) . We conclude that in this group of women with breast findings , most of which were not currently serious enough to warrant biopsy , there was no beneficial effect of vitamin E taken during a 2-month course PURPOSE To evaluate the influence of short-term antioxidant supplementation on retinal function in age-related maculopathy ( ARM ) patients by recording focal electroretinograms ( FERGs ) . DESIGN Nonr and omized , comparative clinical trial . PARTICIPANTS Thirty patients with early ARM and visual acuity > /=20/30 , divided into two groups , similar for age and disease severity : antioxidant group ( ARM-A , n = 17 ) and no treatment group ( ARM-NT , n = 13 ) . Eight age-matched normal subjects divided into antioxidant ( N-A , n = 4 ) or no treatment ( N-NT , n = 4 ) groups . METHODS ARM-A patients and N-A patients had oral supplementation of lutein , 15 mg ; vitamin E , 20 mg ; and nicotinamide , 18 mg , daily for 180 days , whereas ARM-NT patients and N-NT patients had no dietary supplementation during the same period . Eight of the 17 ARM-A patients took supplementation for an additional 180-day period . In all patients and normal subjects , FERG assessment was performed at the study entry ( baseline ) and after 180 days . Further testing was performed at 360 days for the eight ARM-A patients taking supplements and for one ARM-A patient who had discontinued supplementation after 180 days . FERGs were recorded in response to a 41-Hz sinusoidally modulated uniform field ( 93.5 % modulation depth ) presented to the macular region ( 18 degrees ) on a light-adapting background . In a subgroup of patients ( 11 ARM-A and 5 ARM-NT ) , whose responses had suitable signal-to-noise ratios , FERGs were also recorded at different stimulus modulation depths between 8.25 % and 93.5 % . MAIN OUTCOME AND MEASURES Amplitude ( in micro V ) and phase ( in degrees ) of the FERG fundamental harmonic component . FERG modulation thresholds , estimated from the value of log modulation depth yielding a criterion response . RESULTS At 180 days , FERGs of ARM-A patients and N-A patients were increased in amplitude ( mean change , 0.11 and 0.15 log micro V , respectively , P < /= 0.01 ) compared with baseline values , whereas no significant changes in FERG amplitudes of ARM-NT patients and N-NT patients were found ( mean change , -0.004 and -0.023 log micro V , respectively ) . In all groups no changes in the FERG phase were found . FERG modulation thresholds decreased with respect to baseline values ( mean change , -0.36 log units , P < 0.01 ) in ARM-A patients , whereas no significant change ( mean change , 0.07 log units ) in ARM-NT patients was seen . At 360 days , FERGs of ARM-A patients taking supplementation were still increased in amplitude with respect to baseline ( P < 0.05 ) but did not differ from those recorded at 180 days . In the patient who had discontinued supplementation , FERG amplitude decreased from the 180 days value , approaching that recorded at baseline . CONCLUSIONS Although this study provides no evidence for the long-term benefit of antioxidants in ARM , the results suggest that increasing the level of retinal antioxidants might influence macular function early in the disease process , as well as in normal aging BACKGROUND Up-regulation of ICAM-1 at the vascular endothelial level is one of the most important promoters in the slow progression of a healthy vessel to an atherosclerotic one . The current study aim ed to evaluate whether low dose of the antioxidant alpha-tocopherol affects the circulating soluble ( s ) ICAM-1 in healthy subjects . METHODS Either alpha-tocopherol E ( 50 I.U./day ) or placebo was r and omly , double-blindly given to 39 healthy male volunteers ( mean age 41.6+/-5.9 years ) over a period of 20 weeks . RESULTS At the baseline , sICAM-1 levels were inversely correlated with alpha-tocopherol concentrations ( r=-0.525 , p<0.0001 ) . Twenty weeks of alpha-tocopherol supplementation ( n=20 subjects ) significantly decreased the circulating sICAM-1 levels ( from 149.2+/-18.4 to 131.5+/-17.2 microg l(-1 ) , p<0.004 ) while it increased the alpha-tocopherol concentrations ( from 25.8+/-5.0 to 31.2+/-5.7 micromol l(-1 ) , p<0.003 ) . No significant changes in plasma sICAM-1 and alpha-tocopherol levels were observed in placebo-treated subjects ( n=19 ) . In actively treated subjects , changes in circulating sICAM-1 were inversely correlated with changes in alpha-tocopherol concentrations ( r=-0.597 , p=0.005 ) . CONCLUSIONS Plasma sICAM-1 concentrations are stable in healthy subjects over a period of 20 weeks while they significantly decreased with low dose of alpha-tocopherol . Thus , antioxidant vitamins are likely to counteract with endothelial changes that could potentially trigger the atherogenetic process It has been suggested that decreased immune responsiveness in the elderly may be counteracted by the antioxidant vitamin E. In a 3-month double-blind placebo-controlled intervention trial among elderly subjects aged 65 years and over we studied the effects of a daily dose of 100 mg dl-alpha-tocopheryl acetate on the cellular immune responsiveness ( n 52 ) measured by the in vitro response of peripheral blood mononuclear cells ( P BMC ) to the mitogens concanavalin A ( ConA ) and phytohaemagglutinin ( PHA ) . Also effects on the humoral immune responsiveness ( n 74 ) were investigated by measuring immunoglobulin (Ig)G , IgG4 and IgA antibody concentrations against various common antigens . In the vitamin E group plasma alpha-tocopherol increased by 51 % ( P = 0.0001 ) during intervention whereas no significant changes were observed in the control group . Initial proliferative P BMC responses differed between the vitamin E group and the control group whereas all other baseline characteristics were comparable . No significant changes were observed in cellular immune responsiveness when adjusted for initial values in either the control group or the vitamin E group and , after the trial period , responses in the two groups were not significantly different . Similarly , in the vitamin E group no significant changes were found in levels of IgG and IgA raised against Penicillium or IgG4 raised against egg , milk , or wheat proteins . In the control group small but significant increases in IgG anti-Penicillium ( P < 0.05 ) and decreases in IgG4 against milk proteins ( P < 0.05 ) were observed . Thus , the results of this study performed with the relatively low dose of 100 mg dl-alpha-tocopheryl acetate do not support the cl aims of a beneficial effect of vitamin E intake on the overall immune responsiveness of elderly subjects Much data have accrued in support of the concept that oxidation of LDL is a key early step in atherogenesis . The most consistent data with respect to micronutrient antioxidants and atherosclerosis appear to relate to alpha-tocopherol ( AT ) , the predominant lipid-soluble antioxidant in LDL . There are scant data on the direct comparison of RRR-AT and all-racemic (rac)-AT on LDL oxidizability . Hence , the aim of the present study was to examine the relative effects of RRR-AT and all-rac-AT on plasma antioxidant levels and LDL oxidation in healthy persons in a dose-response study . The effect of RRR-AT and all-rac-AT at doses of 100 , 200 , 400 , and 800 IU/d on plasma and LDL AT levels and LDL oxidation was tested in a r and omized , placebo-controlled study of 79 healthy subjects . Copper-catalyzed oxidation of LDL was monitored by measuring the formation of conjugated dienes and lipid peroxides over an 8-hour time course at baseline and again after 8 weeks . Plasma AT , lipid-st and ardized AT , and LDL AT levels rose in a dose-dependent fashion in both the RRR-AT and all-rac-AT groups compared with baseline . There were no significant differences in plasma , lipid-st and ardized , and LDL AT levels between RRR-AT and all-rac-AT supplementation at any dose comparison . The lag phases of oxidation were significantly prolonged with doses > or = 400 IU/d of RRR-AT and all-rac-AT , as measured by conjugated-dienes assay and at 400 IU/d of RRR-AT and 800 IU/d of both forms of AT by lipid peroxide assay . Again , there were no significant differences in the lag phase of oxidation at each dose for RRR-AT when compared with all-rac-AT . Also , there were no significant differences in LDL oxidation after in vitro enrichment of LDL with RRR-AT and all-rac-AT . Thus , supplementation with either RRR-AT or all-rac-AT result ed in similar increases in plasma and LDL AT levels at equivalent IU doses , and the degree of protection against copper-catalyzed LDL oxidation was only evident at doses > or = 400 IU/d for both forms Up-regulation of vascular cell adhesion molecule-1 ( VCAM-1 ) and reduced nitric oxide ( NO ) availability represent early characteristics of atherosclerosis . To evaluate whether the antioxidant vitamin E affected the circulating levels of soluble VCAM-1 ( sVCAM-1 ) and the plasma metabolite of NO ( nitrite+nitrate ) in hypercholesterolemic patients , either vitamin E ( either 400 IU or 800 IU/d for 8 wk ) or placebo were r and omly , double-blindly given to 36 hypercholesterolemic patients and 22 age- and sex-matched controls . At baseline hypercholesterolemic patients showed higher plasma sVCAM-1 ( microg.liter(-1 ) ) ( 591.2 + /- 132.5 vs. 505.0 + /- 65.6 , P < 0.007 ) and lower NO metabolite ( microM ) levels ( 15.9 + /- 3.4 vs. 29.2 + /- 5.1 , P < 0.0001 ) than controls . In hypercholesterolemic patients , 8 wk vitamin E ( but not placebo ) treatment significantly decreased circulating sVCAM-1 levels ( 400 IU : -148.9 + /- 84.6 , P < 0.009 ; 800 IU : -204.0 + /- 75.7 , P < 0.0001 ; placebo : -4.7 + /- 22.6 , NS ) , whereas it increased NO metabolite concentrations ( 400 IU : + 4.0 + /- 1.7 , P < 0.02 ; 800 IU : + 5.5 + /- 0.8 , P < 0.0001 ; placebo : + 0.1 + /- 1.1 , NS ) without affecting circulating low- density lipoprotein levels . Changes in both plasma sVCAM-1 and NO metabolite levels showed a trend to significantly correlate ( r = -0.515 , P = 0.010 ; and r = 0.435 , P = 0.034 , respectively ) with changes in vitamin E concentrations induced by vitamin E supplementation . In conclusion , isolated hypercholesterolemia both increased circulating sVCAM-1 and reduced NO metabolite concentrations . Vitamin E supplementation counteracts these alterations , thus representing a potential tool for endothelial protection in hypercholesterolemic patients Over a 4-year period in a chemoprevention trial on large bowel neoplasia , 58 patients with familial adenomatous polyposis were treated with 4 g of ascorbic acid ( vitamin C)/day plus 400 mg of alpha-tocopherol ( vitamin E)/day alone or with a grain fiber supplement ( 22.5 g/day ) . In this r and omized , double-blind , placebo-controlled study , we determined the effects of these supplements on rectal polyps in these patients . Analysis by intent to treat suggested that the high-fiber supplement had a limited effect . Analysis adjusted for patient compliance showed a stronger benefit from the high-fiber supplement during the middle 2 years of the trial . The results provide evidence for inhibition of benign large bowel neoplasia by grain fiber supplements in excess of 11 g/day in this study population . The findings are consistent with the hypothesis that dietary grain fiber and total dietary fat act as competing variables in the genesis of large bowel neoplasia Patients with diabetes mellitus have an increased risk of premature atherosclerosis , which may be due in part to increased oxidizability of low-density lipoprotein ( LDL ) . Numerous studies have shown that alpha-tocopherol can reduce the oxidative susceptibility of LDL in normoglycemic subjects ; however , there are few studies in persons with diabetes . In addition , alpha-tocopherol may reduce the extent of protein glycation . Therefore , the objective of the present study was to assess the effect of RRR-alpha-tocopheryl acetate supplementation on LDL oxidizability and protein glycation in persons with diabetes without evidence of vascular disease . Twenty-eight persons with insulin-dependent diabetes mellitus ( IDDM ) and non-insulin-dependent diabetes mellitus ( NIDDM ) were r and omly assigned to receive either placebo or 1632 mg ( 1200 IU ) RRR-alpha-tocopherol/d , as tocopheryl acetate , for 8 wk . Plasma and LDL antioxidant concentrations and LDL oxidizability were assessed at both 0 and 8 wk . Plasma and LDL concentrations of alpha-tocopherol were significantly increased in the supplemented group only . Compared with the placebo group , the alpha-tocopherol-supplemented group had significant reductions in LDL oxidizability at 8 wk , as shown by the time-course curves of conjugated diene and lipid peroxide formation . Also , alpha-tocopherol supplementation produced a significant prolongation in the lag phases of both assays , which was evident in both the NIDDM and IDDM subgroups . However , there were no significant changes in glycated hemoglobin or in glycated plasma proteins after alpha-tocopherol supplementation . Thus , alpha-tocopherol supplementation may be beneficial in reducing LDL oxidizability in patients with diabetes The mechanisms responsible for the protective role of selenium against the development of prostate cancer remain to be determined ( L. C. Clark et al. , J. Am . Med . Assoc . , 276 : 1957 - 1963 , 1996 ) . In the present study , we tested the hypothesis that selenium supplementation reduces oxidative stress . A secondary aim was to determine whether selenium-induced changes in testosterone ( T ) metabolism may also be involved . To this end , we conducted a double-blind , r and omized , placebo-controlled trial of 247 micro g selenium/day administered p.o . in the form of Se-enriched yeast . Study subjects were 36 healthy adult males , 11 blacks and 25 whites , 19 - 43 years of age . Supplementation occurred over the first 9 months , after which all subjects were placed on placebo for an additional 3 months . Blood and urine were collected at baseline and after 3 , 9 , and 12 months . In the selenium group , plasma selenium levels were 2-fold higher than baseline values after 3 and 9 months and returned to 136 % of baseline after 12 months ( P < 0.0001 ) , whereas in the placebo group , levels were unchanged . A 32 % increase in blood glutathione ( GSH ) levels was observed after 9 months in the selenium group only ( P < 0.05 ) . This change coincided with a 26 % decrease in protein-bound GSH ( bGSH ) and a 44 % decrease in bGSH : GSH ratios ( P < 0.05 ) . The changes in GSH and bGSH were highly correlated with changes in plasma selenium concentrations and may reflect a decrease in oxidative stress . No changes were observed in either group for plasma T , dihydrotestosterone ( DHT ) or DHT : T ratios , suggesting that selenium had no effect on the alpha-reductase involved in the conversion of T to DHT . A small but significant decrease in prostate-specific antigen levels was observed after 3 and 9 months ( P < 0.001 ) , and this difference disappeared after 12 months . Future trials will test the above hypothesis in prostate cancer patients and in subjects at high risk for prostate cancer To test whether alpha-tocopherol prevents restenosis following percutaneous transluminal coronary angioplasty ( PTCA ) , we enrolled patients in a double-blind , placebo-controlled trial . Patients were r and omized after successful PTCA to receive vitamin E in the form of dl-alpha-tocopherol , 1200 IU/day , orally vs an inactive placebo for 4 months . Patients ' blood was analyzed at baseline and at 4 months post-PTCA for differences in plasma lipids , lipoproteins , apolipoproteins , alpha-tocopherol , retinol , beta-carotene and lipoperoxide concentrations . One hundred patients completed the protocol . No significant difference was found in any parameter except alpha-tocopherol level between the vitamin E group and the placebo group , verifying compliance . Follow-up cardiac catheterization was obtained in 83 % of the patients receiving placebo and in 86 % of the patients receiving dl-alpha-tocopherol . Including thallium and exercise stress testing , objective information was obtained for practically all the patients receiving dl-alpha-tocopherol or placebo . Restenosis was defined as the presence of a lesion with greater than or equal to 50 % stenosis in a previously dilated artery segment and results were analyzed with respect to pre- and post-PTCA artery diameter , vessel diameter at follow-up , and restenosis rate . Patients receiving dl-alpha-tocopherol had a 35.5 % restenosis angiographically documented vs 47.5 % restenosis in patients receiving the placebo . The overall incidence of restenosis defined by an abnormal angiogram or thallium test or exercise stress test was 34.6 % in patients receiving dl-alpha-tocopherol and 50 % in patients receiving the placebo . This difference ( p = 0.06 ) did not reach significance because of an inadequate sample size OBJECTIVE : Obesity is an increasing problem for industrialized nations . The incidence of colorectal cancer has also risen during the last decades . However , information is scarce about the association between the colorectal cancer precursors , adenomatous polyps , and body composition . Our aim was to find out if body fatness is related to the presence of polyps and of growth of adenomas of ≤9 mm observed in situ over 3 yr . METHODS : Twenty-eight out patients with colorectal polyps and 50–75 yr of age were compared with 34 sex- and age-matched ( ±5 yr ) polyp-free healthy controls . The polyp patients were r and omly selected from a double blind 3-yr placebo-controlled endoscopic follow-up and intervention study against growth and recurrence of polyps among 116 polyp-bearing out patients . Triceps skinfold thickness ( TSF ) was measured by a Harpenden caliper and total body fat percentage ( BF% ) by Futrex 5000 . Dietary intake was calculated in a 5-day dietary record by weighing . Demograpic data , including smoking and alcohol habits , were registered by an interview and self-administrated question naires . Weight and height were measured . RESULTS : TSF and BF% ranked 66 % of the individuals into the same quartiles , and 34 % were ranked into the adjacent quartiles . The coefficient of correlation between TSF and BF% was highly significant ( r = 0.90 , p < 0.01 , n = 62 ) . TSF , BF% , and body mass index ( kg/m2 ) did not differ between polyp patients and controls in either crude or adjusted analyses . Adenoma growth was , however , highly associated with increasing levels of TSF ( p = 0.004 ) , BF% ( p = 0.02 ) , and body mass index ( p = 0.006 ) . CONCLUSIONS : Our data suggest that high body fatness is a promoter of adenoma growth . Similar results were obtained with the caliper and Futrex 5000 , which lends credibility to this study . For repeated documentation , a larger study population should be investigated . To our knowledge , this is the first case-control study to investigate the relationship between body composition and growth of adenoma by follow-up in situ over 3 yr In order to gain insight into the causality of the relation between beta-carotene and cancer , we performed a r and omized placebo-controlled trial in which the effect of beta-carotene on the regression and progression rates of cervical dysplasia were examined . The experimental group ( n = 137 ) received a supplemental dose of 10 mg of beta-carotene daily for 3 months . The control group ( n = 141 ) received placebo capsules . As the outcome parameter , two definitions of regression and progression were used , which were based on the degree of dysplasia before and after the medication period . The number of patients who showed progression was too small to allow conclusions . No effect of beta-carotene on the regression percentages was observed : OR = 0.68 ( 95 % CI : 0.28 - 1.60 ) using the broad definition ; and OR = 1.22 ( 95 % CI : 0.43 - 3.41 ) with the strict definition . A secondary analysis , in which the effect of the total intake of beta-carotene ( diet + medication ) on the regression percentages of cervical dysplasia was studied , did not show a positive effect either . The paper discusses to what extent issues in the study design may have masked a potential effect and how our results affect the evidence for a causal relation between beta-carotene and cancer OBJECTIVE The purpose of this report is to analyze the results of a 1-year clinical study of antioxidant therapy in the treatment of pain and recurrent inflammatory episodes in patients with chronic and acute recurrent pancreatitis , using a prospect i ve , descriptive , pre-post , open design . The intensity of pain at the beginning and end of treatment was assessed with a visual analogue scale , and these results along with the number of hospital admissions for pancreatic disease were analyzed . METHODS We studied patients with acute recurrent or chronic pancreatitis who had suffered from pain or acute inflammatory episodes the year before the beginning of treatment with a complex containing L-methionine , beta-carotene , vitamin C , vitamin E and organic selenium . RESULTS Of 10 patients with chronic pancreatitis who completed treatment , the intensity of pain was reduced considerably in 9 ( 61.5 + /- 21.5 mm vs. 19.6 + /- 26.1 mm , p = 0.03 ) , and pain was completely absent in 3 of these patients . Twelve patients who completed treatment had fewer hospital admissions during the year with antioxidant treatment than they had had during the previous year ( 1.5 + /- 1.62 vs. 0.25 + /- 0.45 admissions , p = 0.03 ) . CONCLUSIONS Antioxidant treatment had a positive effect in patients who suffered from pancreatic inflammatory pain , and its effectiveness should be tested before more aggressive and costlier treatments are considered OBJECTIVE In this clinical trial we studied whether oral supplementation with D-alpha-tocopherol ( alpha-Toc ) , L-ascorbic acid ( Asc ) , or alpha-Toc combined with Asc influenced the solar simulated radiation ( SSR ) induced skin inflammation in healthy volunteers . METHODS We investigated the following groups in a prospect i ve , r and omized and placebo controlled study : Group ( 1 ) alpha-Toc 2 g/day , group ( 2 ) Asc 3 g/day , group ( 3 ) alpha-Toc 2 g/day combined with Asc 3 g/day , and group ( 4 ) placebo . Before and 50 days after supplementation we analyzed alpha-Toc and Asc concentrations in keratinocytes . The dose response curve of UV erythema was determined by reflectance spectrophotometry and the minimal erythema dose ( MED ) by visual grading before and after supplementation . RESULTS 50 days after supplementation alpha-Toc keratinocyte levels were increased in groups ( 1 ) and ( 3 ) , Asc concentrations were elevated in groups ( 2 ) and ( 3 ) , and the a/gamma-Toc ratio increased in groups ( 1 ) and ( 3 ) . The dose response curve of UVR induced erythema showed a significant flattening and the MED increased from 103 + /- 29 mJ/cm2 ( before supplementation ) to 183 + /- 35 mJ/cm2 ( after supplementation ) in group ( 3 ) , while there were no significant changes in groups ( 1 ) and ( 2 ) after vitamin supplementation . CONCLUSION Alpha-Toc and Asc act synergistically in suppression of the sunburn reaction A placebo-controlled double-blind intervention trial was performed using 60 male volunteers aged between 50 and 70 years to test the hypothesis that intake of d-alpha-tocopherol ( VITE ) above the recommended dietary intake ( RDI ) level ( 10.0 mg or 14.9 IU VITE ) can protect against DNA damage in human peripheral blood lymphocytes . The intervention consisted of two phases , each of 8 weeks duration : during the initial phase the VITE supplement was 5 x RDI ( provided in cereal ) and during the second phase the VITE supplement was 30 x RDI ( provided in capsules ) . Blood sample s were collected before the initial phase , between phases and at the end of the second phase ; the level of VITE was measured in plasma using HPLC and genetic damage rate in peripheral blood lymphocytes was measured using the cytokinesis-block micronucleus assay . The study has shown that cereal supplementation is an effective route for an above RDI intake of VITE ; a 5 x RDI supplement result ed in a 22 % elevation in the plasma VITE status . By comparison the use of 30 x RDI supplementation with capsules as the route of delivery result ed in an 89 % increment in plasma VITE status . The increased VITE status during the intervention , however , had no significant impact on the spontaneous genetic damage rate in human lymphocytes . There was also no correlation between baseline genetic damage frequency and VITE status . However , a 32 % ( P < 0.007 ) decrease in the micronucleus index was recorded in both the control and VITE-supplemented groups during the course of the study which could have been due either to seasonal effects or other common components in the diet such as the carrier used for the VITE in the cereal and the capsules . The study has identified a small proportion ( 3.4 % ) of apparently healthy individuals who are abnormally sensitive to oxidative stress by hydrogen peroxide and demonstrated that VITE supplementation did not attenuate the impact of the oxidative challenge on genetic damage rate . The above data suggest that supplements in cereal are a viable route for delivering VITE and that supplementation with VITE is unlikely to affect chromosome damage occurring spontaneously or as a result of exposure to oxidative radicals The accumulated data indicate that asthma is associated with reduced circulatory selenium ( Se ) status and lowered activity of the Se-dependent enzyme glutathione peroxidase ( GSH-Px ) , which may have etiological implication s , considering the important role of GSH-Px in the cellular elimination of hydroperoxides . The aim of the present double-blind study was to investigate whether Se supplementation in asthmatic patients may increase GSH-Px activity and possibly bring about clinical improvement . Twenty-four patients suffering from intrinsic asthma were selected and r and omized into two groups , and after a preintervention period of 4 weeks , one group received a daily supplement of 100 micrograms sodium selenite for 14 weeks , whereas the other group received placebo . In the Se-supplemented group there were significant increases in serum Se and platelet GSH-Px activity after intervention , accompanied by a significant reduction in the irreversible platelet aggregation induced by 5 mumol/l ADP , while no significant changes in these parameters could be observed in the placebo group . Further , there was a significant clinical improvement in the Se-supplemented group , as compared with the placebo group , with regard to the assembled clinical evaluation made of each patient . This improvement could , however , not be vali date d by significant changes in the separate clinical parameters of lung function and airway hyperresponsiveness . The results are discussed in view of the role of GSH-Px in the cellular enzymatic oxidant defense system and as a modulator of arachidonic acid metabolism Twelve clinical ly healthy subjects participated in a vitamin E supplementation study . Eight were given daily dosages of 150 , 225 , 800 , or 1200 IU RRR-alpha-tocopherol for 21 days ( two persons per dose ) and four received placebo . Prior , during , and after the supplementation period , alpha-tocopherol , gamma-tocopherol , and carotenoids were determined in plasma and low density lipoprotein ( LDL ) . The maximum levels of alpha-tocopherol were 1.7- to 2.5-times the baseline values in plasma and 1.7- to 3.1-times in LDL . A high correlation existed between alpha-tocopherol in plasma and LDL . gamma-Tocopherol significantly decreased in plasma and LDL during vitamin E supplementation . No significant influence on the lipoprotein and lipid status and carotenoid levels of the participants occurred throughout the supplementation . The resistance of LDL against copper-mediated oxidation was also measured . The oxidation resistance of LDL was significantly higher during vitamin E supplementation . However , the efficacy of vitamin E in protecting LDL varied from person to person . The statistical evaluation of all data gave a correlation of r2 = 0.51 between alpha-tocopherol in LDL and the oxidation resistance as measured by the length of the lag-phase preceding the oxidation of LDL . No association was seen between levels of carotenoids and vitamin E in plasma and LDL . The present study clearly shows that in humans the oxidation resistance of LDL can be increased by vitamin E supplementation Since reduced concentrations of selenium in whole blood , plasma and white cells had previously been observed in psoriasis , 69 patients were supplemented daily with either 600 μg of selenium-enriched yeast , 600 μg of selenium-enriched yeast plus 600 IU of vitamin E or a placebo for 12 weeks . Before supplementation , the patients ' mean concentrations of selenium in whole blood and plasma were reduced compared with those of matched healthy controls but their red cell glutathione peroxidase ( GSH-Px ) activity was normal . After 12 weeks supplementation the patients ' mean whole blood , plasma and platelet selenium concentrations , platelet GSH-Px activity and plasma vitamin E concentration had risen significantly from the baseline values but their mean skin selenium concentration and red cell GSH-Px activity remained unchanged . The mean white cell selenium concentration rose only in the group receiving selenium alone . Neither supplementation regimen reduced the severity of psoriasis or produced side-effects . The increase in platelet GSH-Px activity suggests that the supplements were bioavailable and that the patients ' selenium status may have been reduced prior to supplementation . The failure of the selenium content of the skin to increase may explain why the patients ' psoriasis remained unchanged during supplementation AIMS Elevated levels of urinary albumin excretion rate ( AER ) predict high risk for progressing to end-stage renal disease . In streptozotocin-induced diabetes , supplementation with vitamin C or E reduces albuminuria and glomerular hypertrophy . We tested the hypothesis that supplementation of both vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with persistent micro/macroalbuminuria . METHODS Thirty Type 2 diabetic patients with AER 30 - 300 mg/24 h were included in a double-blind r and omised , cross-over trial . Patients received vitamin C ( 1250 mg ) and vitamin E ( 680 IU ) per day or matching placebo for 4 weeks with a 3-week wash-out period between treatment periods in r and om order . RESULTS Combined treatment with vitamin C and E reduced AER by 19 % ( 95 % CI 6 - 34 % ) ( p = 0.04 ) , geometric mean 197 mg/24 h ( 95 % CI 114 - 341 mg/24 h ) vs. 243 mg/24 h ( 146 - 404 mg/24 h ) . No changes were seen in serum creatinine , haemoglobin A1C or blood pressure . Fasting plasma concentrations of vitamin C and E increased in all patients during active treatment ( mean vitamin C 79.4 micromol/L ( SD 27.8 ) vs. 41.9 micromol/L ( 18.4 ) and vitamin E 47.0 micromol/L ( 19.8 ) vs. 29.5 micromol/L ( 15.3 ) , P < 0.000001 ) . Except for two patients that started additional blood pressure lowering treatment during the run-in period , no changes in medication , food and exercise habits or in the number of smokers occurred during the study . CONCLUSION Short-term treatment with vitamin C and E in pharmacological doses lowers AER in Type 2 diabetic patients with micro/macroalbuminuria . Further long-term , large-scale studies of this albuminuria reducing treatment modality are warranted In a double-blind placebo controlled trial , the efficacy of Vitamin E in the treatment of tardive dyskinesia ( TD ) was studied in 32 patients . After a two week wash-out phase a baseline ( 0 week ) TD rating was assessed on the tardive dyskinesia rating scale ( TDRS ) . Subsequently , the patients entered a four week treatment phase during which 17 patients received capsules of vitamin E ( 600 mg ) and 15 patients received identical placebo capsules . In the first week the patients received 1 capsule daily which was then increased to two capsules per day from the second to the fourth week . All patients were rated on the TDRS at the end of each week . The baseline TDRS score in the vitamin E group was significantly higher than the placebo group . This was hence adjusted and the results were then subjected to analysis of co- variance . The TDRS score after four weeks treatment was significantly lower in the vitamin E group as compared to the placebo group ( p = 0.03 ) Objective : The purpose of this study was to determine the effect of vitamin E and /or vitamin C supplementation on low-density lipoprotein ( LDL ) oxidizability and neutrophil ( PMN ) superoxide anion production in young smokers . Methods : Thirty smokers with a < 5 pack-year history were r and omly assigned to take placebo ; vitamin C ( 1 g/day ) ; vitamin E ( 400 IU/day ) ; or both vitamins in a double-blind fashion . Subjects took the supplements for 8 weeks . At weeks 0 and 8 , blood was collected for isolation of LDL and PMN , and for antioxidant vitamin analysis . LDL was oxidized with a copper ( Cu ) catalyst , and oxidation was measured by formation of conjugated dienes over a 5-hour time course . Lag times and maximum oxidation rates were calculated from the time course data . PMN superoxide anion release was assessed by respiratory burst after stimulation with phorbol ester and opsonized zymosan , and their ability to oxidize autologous LDL following treatment with the above stimuli was measured with the conjugated diene assay . Results : Subjects who received vitamin E alone had a significant increase in the lag phase of Cu-catalyzed LDL oxidation ( week 0 , 118 ± 31 min vs. week 8 , 193 ± 80 min , mean ± SD , p < 0.05 ) , whereas the vitamin C and placebo groups had no changes in LDL oxidation kinetics . The group receiving both vitamins E and C had a significant reduction in oxidation rate ( week 0 , 7.4 ± 2.3 vs. week 8 , 5.1 ± 2.1 , p < 0.05 ) . There were no significant changes for any group in PMN superoxide anion production or PMN LDL oxidation after stimulation with either phorbol ester or opsonized zymosan . Plasma and LDL vitamin E concentrations were significantly increased in both groups that received vitamin E. The subjects who received vitamin C alone had no significant change in plasma vitamin C concentrations ; however , when data were pooled from both groups who received vitamin C , the increases were significant . Conclusion : Vitamin E supplementation of young smokers was effective in reducing Cu-catalyzed LDL oxidizability ; however , vitamin E and /or C supplementation showed few significant effects on the more physiologically relevant PMN function . This casts doubt on the ability of antioxidant supplementation to reduce oxidative stress in smokers in vivo . Therefore , smoking cessation remains the only means by which young smokers can prevent premature coronary heart disease BACKGROUND Recent studies have suggested that alpha-tocopherol supplementation can help reduce the incidence of coronary disease . Our objectives were to determine the feasibility of providing alpha-tocopherol supplements to male veterans with existing coronary artery disease and determine its effects on alpha-tocopherol levels and the susceptibility of low-density lipoprotein ( LDL ) to oxidation . METHODS Fifty-seven percent of 138 coronary disease patients were willing to participate in a placebo-controlled trial -25 % were already taking antioxidants . Thirty-nine men were r and omly assigned to either 400 mg/day of alpha-tocopherol ( n = 27 ) or placebo ( n = 12 ) . alpha-Tocopherol levels and LDL oxidation ( measured by formation of thiobarbituric acid-reactive substance ) were measured at baseline and at 6 months . RESULTS Thirty-three subjects ( 22 alpha-tocopherol , 11 placebo ) completed the study ; 3 subjects withdrew after suffering coronary disease events . Supplement compliance exceeded 90 % and alpha-tocopherol was well tolerated . The alpha-tocopherol group had a significantly greater mean increase in lipid-adjusted alpha-tocopherol levels ( 73 % vs. -4.6 % , P < 0.0001 ) , but oxidized LDL did not change significantly . CONCLUSIONS A secondary prevention trial among veterans would be feasible because the rates of enrollment , completion , compliance , and clinical events were high . alpha-Tocopherol supplements did not decrease the susceptibility of LDL to oxidation , suggesting that higher dosages or longer duration of supplementation may be required for secondary prevention Objectives To determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids . Design A 6-month double-blind r and omized placebo-controlled cross-over study with a 1-week washout between cross-over periods . Methods Vitamin C 500 mg daily or matching placebo was given to 40 men and women aged between 60 and 80 years for 3 months each in a cross-over fashion . Clinic and 24-h ambulatory blood pressure , plasma ascorbate and lipids were measured at baseline and at the end of each cross-over phase . Results Clinic blood pressure did not change between placebo and vitamin C phases . Daytime ambulatory blood pressure showed a small but significant fall in systolic blood pressure ( 2.0 ± 5.2 mmHg ; 95 % confidence interval 0–3.9 mmHg ) but not in diastolic blood pressure . Regression analysis showed that with increasing baseline daytime blood pressure the fall in blood pressure with vitamin C supplementation increased . Regression analysis of the change in high-density lipoprotein ( HDL ) cholesterol showed a significant effect of sex on the change in HDL cholesterol . In women , but not men , HDL cholesterol increased significantly by 0.08 ± 0.11 mmol/l , P = 0.007 . There was no change in low-density lipoprotein cholesterol between treatment periods . Conclusion In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure , which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke The effect of vitamin C on blood pressure is not well established . This is a r and omized , double-blind control trial . Eligible patients were followed for 8 months . Patients were r and omized to 500 , 1000 , or 2000 mg vitamin C. During each visit , a history including medication change was obtained and st and ardized blood pressure measurements were performed . A 1-week dietary diary was filled out before each visit . Multiple regression analysis and subsequent multiple comparisons were used for data analysis . Fifty-four patients satisfied our criteria and agreed to participate . Thirty-one patients ( mean age , 62 ± 2 years ; 52 % men , 90 % whites ) were r and omized to the three doses of vitamin C. Overall compliance was 48 ± 2 % . Both mean systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) decreased during the vitamin C supplementation phase [ mean SBP dropped by 4.5 ± 1.8 mm Hg ( P < .05 ) and DBP by 2.8 ± 1.2 mm Hg ( P < .05 ) ] . There was no difference between the three vitamin C groups ( P = .48 ) . This effect was significant for only 1 month of supplementation , but the trend persisted . There was no reported intolerance to vitamin C. There was no change in lipid levels after 6 months of treatment . Vitamin C supplementation lowers blood pressure in mildly hypertensive patients . There is no additional benefit for a higher dose than 500 mg daily . The effect of vitamin C is most likely to be only short term |
12,809 | 29,084,085 | Conclusion : The results of this meta- analysis indicate that restriction of dietary sodium intake reduces arterial stiffness .
This effect seems be at least in part independent of the changes in blood pressure | Objective : Arterial stiffness is an independent cardiovascular risk factor and sodium intake could be a determinant of arterial stiffness .
Nevertheless , the studies that investigated the effect of reducing dietary sodium intake on arterial stiffness in humans provided inconsistent results .
Therefore , we performed a systematic review and a meta- analysis of the available r and omized controlled trials of salt restriction and arterial stiffness to try and achieve more definitive conclusions . | A reduction in salt intake lowers blood pressure . However , most previous trials were in whites with few in blacks and Asians . Salt reduction may also reduce other cardiovascular risk factors ( eg , urinary albumin excretion , arterial stiffness ) . However , few well-controlled trials have studied these effects . We carried out a r and omized double-blind crossover trial of salt restriction with slow sodium or placebo , each for 6 weeks , in 71 whites , 69 blacks , and 29 Asians with untreated mildly raised blood pressure . From slow sodium to placebo , urinary sodium was reduced from 165±58 ( ±SD ) to 110±49 mmol/24 hours ( 9.7 to 6.5 g/d salt ) . With this reduction in salt intake , there was a significant decrease in blood pressure from 146±13/91±8 to 141±12/88±9 mm Hg ( P<0.001 ) , urinary albumin from 10.2 ( IQR : 6.8 to 18.9 ) to 9.1 ( 6.6 to 14.0 ) mg/24 hours ( P<0.001 ) , albumin/creatinine ratio from 0.81 ( 0.47 to 1.43 ) to 0.66 ( 0.44 to 1.22 ) mg/mmol ( P<0.001 ) , and carotid-femoral pulse wave velocity from 11.5±2.3 to 11.1±1.9 m/s ( P<0.01 ) . Subgroup analysis showed that the reductions in blood pressure and urinary albumin/creatinine ratio were significant in all groups , and the decrease in pulse wave velocity was significant in blacks only . These results demonstrate that a modest reduction in salt intake , approximately the amount of the current public health recommendations , causes significant falls in blood pressure in all 3 ethnic groups . Furthermore , it reduces urinary albumin and improves large artery compliance . Although both could be attributable to the falls in blood pressure , they may carry additional benefits on reducing cardiovascular disease above that obtained from the blood pressure falls alone There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD , particularly in patients with pre-end stage CKD , where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events . We conducted a double-blind placebo-controlled r and omized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP , 24-hour protein and albumin excretion , fluid status ( body composition monitor ) , renin and aldosterone levels , and arterial stiffness ( pulse wave velocity and augmentation index ) in 20 adult patients with hypertensive stage 3 - 4 CKD as phase 1 of the LowSALT CKD study . Overall , salt restriction result ed in statistically significant and clinical ly important reductions in BP ( mean reduction of systolic/diastolic BP , 10/4 mm Hg ; 95 % confidence interval , 5 to 15 /1 to 6 mm Hg ) , extracellular fluid volume , albuminuria , and proteinuria in patients with moderate-to-severe CKD . The magnitude of change was more pronounced than the magnitude reported in patients without CKD , suggesting that patients with CKD are particularly salt sensitive . Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits , this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression The role of salt restriction in patients with impaired glucose tolerance and diabetes mellitus is controversial , with a lack of well controlled , longer term , modest salt reduction trials in this group of patients , in spite of the marked increase in cardiovascular risk . We carried out a 12-week r and omized double-blind , crossover trial of salt restriction with salt or placebo tablets , each for 6 weeks , in 46 individuals with diet-controlled type 2 diabetes mellitus or impaired glucose tolerance and untreated normal or high normal blood pressure ( BP ) . From salt to placebo , 24-hour urinary sodium was reduced by 49±9 mmol ( 2.9 g salt ) . This reduction in salt intake led to fall in clinic BP from 136/81±2/1 mm Hg to 131/80±2/1 mm Hg , ( systolic BP ; P<0.01 ) . Mean ambulatory 24-hour BP was reduced by 3/2±1/1 mm Hg ( systolic BP , P<0.01 and diastolic BP , P<0.05 ) , and albumin/creatinine ratio was reduced from 0.73 mg/mmol ( 0.5–1.5 ) to 0.64 mg/mmol ( 0.3–1.1 ; P<0.05 ) . There was no significant change in fasting glucose , hemoglobin A1c , or insulin sensitivity . These results demonstrate that a modest reduction in salt intake , to approximately the amount recommended in public health guidelines , leads to significant and clinical ly relevant falls in BP in individuals who are early on in the progression of diabetes mellitus with normal or mildly raised BP . The reduction in urinary albumin excretion may carry additional benefits in reducing cardiovascular disease above the effects on BP Objective High salt intake is known to be the most pivotal environmental factor in the pathogenesis of hypertension . However , the association of high sodium intake with central hemodynamics in hypertensive individuals has not been well defined . Here , we determined the association of estimated 24-h urine sodium and potassium excretion estimated from a spot urine analysis with parameters of central pulse wave analysis in 515 hypertensive individuals . Methods Fasting spot urine sample s were obtained in the early morning after the first void , and estimated 24-h urine sodium and potassium excretion were estimated from measurement of urine sodium , potassium and creatinine . Central hemodynamics and arterial stiffness parameters were assessed via pulse wave analysis of the radial artery . Results The estimated 24-h sodium and potassium excretion values were 150 ± 40 and 49 ± 10 mEq , respectively . There was a step-wise decrease in pulse pressure amplification with increasing estimated 24-h urine sodium excretion . Multiple linear regression analyses revealed that both estimated 24-h urine sodium excretion and sodium/potassium ratio were independently associated with increases in central pulse pressure , augmented aortic pressure and augmentation index and were inversely associated with pulse pressure amplification . Conclusion The estimated 24-h urinary sodium excretion is independently associated with central hemodynamics . This may provide the basis for prospect i ve interventional studies of epidemiologic scale to determine the potential beneficial effects of reduced salt consumption on central hemodynamics We tested the hypothesis that the Na+ component of dietary NaCl can have a pressor effect apart from its capacity to complement the extracellular osmotic activity of Cl− and , thus , exp and plasma volume . We studied 35 mostly normotensive blacks who ingested a low-NaCl diet , 30 mmol/d , for 3 weeks , in the first and third of which Na+ was loaded orally with either NaHCO3 or NaCl , in r and om order ( 250 mmol/d ) . In subjects adjudged to be salt sensitive ( n=18 ; & Dgr ; mean arterial pressure : ≥5 mm Hg with NaCl load ) , but not in salt-resistant subjects ( n=17 ) , loading with NaHCO3 was also pressor . The pressor effect of NaHCO3 was half that of NaCl : mean arterial pressure ( millimeters of mercury ) increased significantly from 90 on low NaCl to 95 with NaHCO3 and to 101 with NaCl . The pressor effect of NaCl strongly predicted that of NaHCO3 . As judged by hematocrit decrease , plasma volume expansion with NaCl was the same in salt-resistant and salt-sensitive subjects and twice that with NaHCO3 , irrespective of the pressor effect . In salt-sensitive subjects , mean arterial pressure varied directly with plasma Na+ concentration attained with all Na+ loading . In salt-sensitive but not salt-resistant subjects , NaHCO3 and NaCl induced decreases in renal blood flow and increases in renal vascular resistance ; changes in renal blood flow were not different with the 2 salts . Responses of renal blood flow and renal vascular resistance to NaHCO3 were strongly predicted by those to NaCl . In establishing the fact of “ sodium-selective ” salt sensitivity , the current observations demonstrate that the Na+ component of NaCl can have pressor and renal vasoconstrictive properties apart from its capacity to complement Cl− in plasma volume expansion BACKGROUND AND OBJECTIVES Systolic BP and large elastic artery stiffness both increase with age and are reduced by dietary sodium restriction . Production of the natriuretic hormone marinobufagenin , an endogenous α1 Na+,K+-ATPase inhibitor , is increased in salt-sensitive hypertension and contributes to the rise in systolic BP during sodium loading . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS The hypothesis was that dietary sodium restriction performed in middle-aged/older adults ( eight men and three women ; 60 ± 2 years ) with moderately elevated systolic BP ( 139 ± 2/83 ± 2 mmHg ) would reduce urinary marinobufagenin excretion as well as systolic BP and aortic pulse-wave velocity ( r and omized , placebo-controlled , and crossover design ) . This study also explored the associations among marinobufagenin excretion with systolic BP and aortic pulse-wave velocity across conditions of 5 weeks of a low-sodium ( 77 ± 9 mmol/d ) and 5 weeks of a normal-sodium ( 144 ± 7 mmol/d ) diet . RESULTS Urinary marinobufagenin excretion ( weekly measurements ; 25.4 ± 1.8 versus 30.7 ± 2.1 pmol/kg per day ) , systolic BP ( 127 ± 3 versus 138 ± 5 mmHg ) , and aortic pulse-wave velocity ( 700 ± 40 versus 843 ± 36 cm/s ) were lower during the low- versus normal-sodium condition ( all P<0.05 ) . Across all weeks , marinobufagenin excretion was related with systolic BP ( slope=0.61 , P<0.001 ) and sodium excretion ( slope=0.46 , P<0.001 ) . These associations persisted during the normal- but not the low-sodium condition ( both P<0.005 ) . Marinobufagenin excretion also was associated with aortic pulse-wave velocity ( slope=0.70 , P=0.02 ) and endothelial cell expression of NAD(P)H oxidase-p47phox ( slope=0.64 , P=0.006 ) . CONCLUSIONS These results show , for the first time in humans , that dietary sodium restriction reduces urinary marinobufagenin excretion and that urinary marinobufagenin excretion is positively associated with systolic BP , aortic stiffness ( aortic pulse-wave velocity ) , and endothelial cell expression of the oxidant enzyme NAD(P)H oxidase . Importantly , marinobufagenin excretion is positively related to systolic BP over ranges of sodium intake typical of an American diet , extending previous observations in rodents and humans fed experimentally high-sodium diets We performed a r and omised , placebo-controlled , crossover study to examine the effects of sodium and potassium supplementation on blood pressure ( BP ) and arterial stiffness in untreated (pre)hypertensive individuals . During the study , subjects were on a fully controlled diet that was relatively low in sodium and potassium . After a 1-week run-in period , subjects received capsules with supplemental sodium ( 3 g d−1 , equals 7.6 g d−1 of salt ) , supplemental potassium ( 3 g d−1 ) or placebo , for 4 weeks each , in r and om order . Fasting office BP , 24-h ambulatory BP and measures of arterial stiffness were assessed at baseline and every 4 weeks . Of 37 r and omized subjects , 36 completed the study . They had a mean pre-treatment BP of 145/81 mm Hg and 69 % had systolic BP ⩾140 mm Hg . Sodium excretion was increased by 98 mmol per 24 h and potassium excretion by 63 mmol per 24 h during active interventions , compared with placebo . During sodium supplementation , office BP was significantly increased by 7.5/3.3 mm Hg , 24-h BP by 7.5/2.7 mm Hg and central BP by 8.5/3.6 mm Hg . During potassium supplementation , 24-h BP was significantly reduced by 3.9/1.6 mm Hg and central pulse pressure by 2.9 mm Hg . Pulse wave velocity and augmentation index were not significantly affected by sodium or potassium supplementation . In conclusion , increasing the intake of sodium caused a substantial increase in BP in subjects with untreated elevated BP . Increased potassium intake , on top of a relatively low-sodium diet , had a beneficial effect on BP . Arterial stiffness did not material ly change during 4-week interventions with sodium or potassium BACKGROUND AND AIM It is unclear if a modest reduction in dietary salt intake has beneficial effects on vascular function . The aim was to compare the effects of 9 g salt/day with 6 g salt/day intake on measures of vascular function and explore mechanisms of effect in overweight and obese adults . METHODS Twenty-five overweight/obese subjects ( BMI 27 - 40 kg/m(2 ) ) completed a r and omised cross-over study of 6 weeks each on a reduced salt ( RS ) ( 6 g/day ) and usual salt diet ( US ) ( 9 g/day ) . Flow-mediated-dilatation ( FMD ) , 24 h blood pressure ( BP ) , augmentation index ( AIx ) , pulse wave velocity ( PWV ) , plasma and urinary nitrate/nitrite , asymmetric dimethylarginine ( ADMA ) , renin , aldosterone and endothelin-1 and vascular adhesion molecules were measured after 2 days and 6 weeks . Adherence to the diets was determined from two 24 h urine collection s. RESULTS Urinary sodium excretion was 155 ± 58 mmol/24 h US vs 113 ± 45 mmol/24 h RS ( p = 0.002 ) . Following the RS diet there was a significant improvement in FMD from 3.5 ± 2.8 % to 5.6 ± 2.8 % ( P < 0.001 ) and decrease in serum endothelin-1 from 1.45 ± 0.38 pg/ml to 1.25 ± 0.39 pg/ml ( P < 0.05 ) . Endothelium-independent vasodilatation was also significantly different between treatments ( P < 0.05 ) . AIx , PWV , serum ADMA and plasma and urinary nitrate/nitrite concentrations were not different between treatments . Change in FMD was related to the urinary sodium : creatinine ratio ( r = -0.47 , P < 0.05 ) and was independent of blood pressure . Aldosterone and renin were unchanged . CONCLUSIONS A small reduction in dietary salt intake of 3 g/day improves endothelial function in normotensive overweight and obese subjects . This response may be mediated by serum endothelin-1 . This small reduction in salt had no effect on aldosterone and renin concentrations . This trial was registered with the Australian and New Zeal and Clinical Trials Registry Unique Identifier : ACTRN12609000321246 http://www.anzctr.org.au/ACTRN12609000321246.aspx Arterial stiffness , estimated by pulse wave velocity ( PWV ) , is an independent predictor of cardiovascular mortality and morbidity . However , the clinical applicability of these measurements and the elaboration of reference PWV values are difficult due to differences between the various devices used . In a population of 50 subjects aged 20–84 years , we compared PWV measurements with three frequently used devices : the Complior and the PulsePen , both of which determine aortic PWV as the delay between carotid and femoral pressure wave and the PulseTrace , which estimates the Stiffness Index ( SI ) by analyzing photoplethysmographic waves acquired on the fingertip . PWV was measured twice by each device . Coefficient of variation of PWV was 12.3 , 12.4 and 14.5 % for PulsePen , Complior and PulseTrace , respectively . These measurements were compared with the reference method , that is , a simultaneous acquisition of pressure waves using two tonometers . High correlation coefficients with the reference method were observed for PulsePen ( r=0.99 ) and Complior ( r=0.83 ) , whereas for PulseTrace correlation with the reference method was much lower ( r=0.55 ) . Upon Bl and –Altman analysis , mean differences of values±2s.d . versus the reference method were −0.15±0.62 m/s , 2.09±2.68 m/s and −1.12±4.92 m/s , for PulsePen , Complior and PulseTrace , respectively . This study confirms the reliability of Complior and PulsePen devices in estimating PWV , while the SI determined by the PulseTrace device was found to be inappropriate as a surrogate of PWV . The present results indicate the urgent need for evaluation and comparison of the different devices to st and ardize PWV measurements and establish reference values This study used a precise noninvasive method in normotensive humans to determine the effects of sympathetic activation on arterial compliance . A recently developed , high-resolution echo-tracking system capable of measuring systolic/diastolic variations of arterial diameter was coupled to a Finapres system and used to calculate instantaneous systolic/diastolic pressure-diameter and compliance-pressure curves for a muscular medium-sized artery , the radial artery . Two st and ardized tests of sympathetic system activation , a cold pressor test ( 2 min ) and a mental stress test ( 2 min of mental arithmetic ) , were performed at an interval of 8 days in r and om order in nine healthy volunteers [ 30 + /- 9 ( SD ) yr ] . Radial arterial parameters were recorded every 30 s for 9 min , which included 2 min of cold pressor test or mental stress test . During both tests , radial arterial mean diameter did not change despite t he increase in mean arterial pressure ( P < 0.001 ) ; stroke change in diameter decreased ( P < 0.01 ) , whereas pulse pressure increased ( P < 0.01 ) . Arterial compliance , calculated for the instantaneous level of mean arterial pressure , decreased significantly ( P < 0.01 ) . Compliance ( C ) calculated at 100 mmHg ( C100 ) was arbitrarily chosen as a reference point for comparing compliance among the different periods of the test . C100 decreased significant ( P < 0.05 ) during both tests ( from 2.93 + /- 1.27 to 2.04 + /- 0.94 and from 3.29 + /- 1.73 to 2.63 + /- 1.55 mm2.mmHg-1.10(-3 ) during mental stress and the cold pressor test , respectively ) . These results indicate that sympathetic activation is able to decrease radial arterial compliance in healthy subjects . The reduction in arterial compliance probably result ed from complex interactions between changes in distending blood pressure and changes in radial arterial smooth muscle tone BACKGROUND Studies of dietary sodium on vascular function and blood pressure in normotensive volunteers have shown conflicting results . There are very limited data available on the effect of chronic sodium loading from a low-sodium diet to a high-sodium diet on vascular function and blood pressure in normotensive volunteers . OBJECTIVE To assess the effect of modifying dietary sodium intake on arterial function and surrogate markers of arterial remodelling in normal healthy volunteers . DESIGN Twenty-three normotensive volunteers met the inclusion criteria . After a 2 week run-in with a low-sodium diet ( 60 mmol/day ) , the participants maintained their low-sodium diets and were r and omly assigned to receive sequentially one of three interventions for 4 weeks , with a 2 week washout between interventions : sodium-free tomato juice ( A ) , tomato juice containing 90 mmol Na ( B ) and tomato juice containing 140 mmol Na ( C ) . The outcomes measured were changes in pulse wave velocity ( PWV ) , systolic blood pressure and diastolic blood pressure . RESULTS There was no difference in PWV between interventions ( B-A 0.00 m/s , 95 % CI : -0.30 , 0.31 m/s ; C-A 0.01 m/s , 95 % CI : -0.38 , 0.40 m/s ) . There was also no change in pulse wave analysis , systolic or diastolic blood pressure between interventions . There was an appropriate increase in urinary sodium excretion in the added sodium interventions . CONCLUSION Dietary salt loading did not produce significant increases in PWV and blood pressure in normotensive subjects with systolic blood pressure < 130 mmHg . The lack of an observed effect supports Guyton 's pressure-natriuresis hypothesis with appropriate renal excretion of the excess sodium load BACKGROUND Studies of sodium have shown improvements in vascular function and blood pressure ( BP ) . The effect of chronic sodium loading from a low-sodium diet to a Western diet on vascular function and BP has been less well studied . OBJECTIVE The objective was to examine the effects of dietary salt intake on vascular function and BP . DESIGN Thirty-five hypertensive volunteers met the inclusion criteria . After a 2-wk run-in with a low-sodium diet ( 60 mmol/d ) , the participants maintained their diets and were r and omly assigned to receive sequentially 1 of 3 interventions for 4 wk , with a 2-wk washout between interventions : sodium-free tomato juice ( A ) , tomato juice containing 90 mmol Na ( B ) , and tomato juice containing 140 mmol Na ( C ) . The outcomes were changes in pulse wave velocity ( PWV ) , systolic BP ( SBP ) , and diastolic BP ( DBP ) . RESULTS The difference in PWV between interventions B and A was 0.39 m/s ( 95 % CI : 0.18 , 0.60 m/s ; P < or = 0.001 ) and between C and A was 0.35 m/s ( 95 % CI : 0.13 , 0.57 m/s ; P < or = 0.01 ) . Differences in SBP and DBP between interventions B and A were 4.4 mm Hg ( 95 % CI : 1.2 , 7.8 mm Hg ; P < or = 0.01 ) and 2.4 mm Hg ( 95 % CI : 0.8 , 4.1 mm Hg ; P < or = 0.001 ) , respectively , and between interventions C and A were 5.6 mm Hg ( 95 % CI : 2.7 , 8.4 mm Hg ; P < or = 0.01 ) and 3.3 mm Hg ( 95 % CI : 1.5 , 5.0 mm Hg ; P < or = 0.001 ) , respectively . Changes in PWV correlated with changes in SBP ( r = 0.52 ) and DBP ( r = 0.58 ) . CONCLUSIONS Dietary salt loading produced significant increases in PWV and BP in hypertensive volunteers . Correlations between BP and PWV suggest that salt loading may have a BP-independent effect on vascular wall function . This further supports the importance of dietary sodium restriction in the management of hypertension . This trial was registered with the Australian and New Zeal and Clinical Trials Registry as ACTRN12609000161224 BACKGROUND The effect of salt reduction on vascular function , assessed by brachial artery flow-mediated dilatation ( FMD ) , is unknown . OBJECTIVE Our aim was to compare the effects of a low-salt ( LS ; 50 mmol Na/d ) diet with those of a usual-salt ( US ; 150 mmol Na/d ) diet on FMD . DESIGN This was a r and omized crossover design in which 29 overweight and obese normotensive men and women followed an LS diet and a US diet for 2 wk . Both diets had similar potassium and saturated fat contents and were design ed to ensure weight stability . After each intervention , FMD , pulse wave velocity , augmentation index , and blood pressure were measured . RESULTS FMD was significantly greater ( P = 0.001 ) with the LS diet ( 4.89 + /- 2.42 % ) than with the US diet ( 3.37 + /- 2.10 % ) , systolic blood pressure was significantly ( P = 0.02 ) lower with the LS diet ( 112 + /- 11 mm Hg ) than with the US diet ( 117 + /- 13 mm Hg ) , and 24-h sodium excretion was significantly lower ( P = 0.0001 ) with the LS diet ( 64.1 + /- 41.3 mmol ) than with the US diet ( 156.3 + /- 56.7 mmol ) . There was no correlation between change in FMD and change in 24-h sodium excretion or change in blood pressure . No significant changes in augmentation index or pulse wave velocity were observed . CONCLUSIONS Salt reduction improves endothelium-dependant vasodilation in normotensive subjects independently of the changes in measured resting clinic blood pressure . These findings suggest additional cardioprotective effects of salt reduction beyond blood pressure reduction . The trial is registered with the Australian and New Zeal and Clinical Trials Registry ( unique identifier : ANZCTR12607000381482 ; http://www.anzctr.org.au/trial_view.aspx?ID=82159 ) |
12,810 | 24,142,810 | Very low quality evidence suggests that third wave CBT approaches appear to be more effective than treatment as usual in the treatment of acute depression . | BACKGROUND So-called ' third wave ' cognitive and behavioural therapies represent a new generation of psychological therapies that are increasingly being used in the treatment of psychological problems .
However , the effectiveness and acceptability of third-wave cognitive and behavioural therapy ( CBT ) approaches as treatment for acute depression remain unclear .
OBJECTIVES 1 .
To examine the effects of all third wave CBT approaches compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.2 .
To examine the effects of different third wave CBT approaches ( ACT , compassionate mind training , functional analytic psychotherapy , dialectical behaviour therapy , MBCT , extended behavioural activation and metacognitive therapy ) compared with treatment as usual/waiting list/attention placebo/psychological placebo control conditions for acute depression.3 .
To examine the effects of all third wave CBT approaches compared with different types of comparators ( treatment as usual , no treatment , waiting list , attention placebo , psychological placebo ) for acute depression . | BACKGROUND Behavioural activation appears as effective as cognitive-behaviour therapy ( CBT ) in the treatment of depression . If equally effective , then behavioural activation may be the preferred treatment option because it may be suitable for delivery by therapists with less training . This is the first r and omised controlled trial to look at this possibility . AIMS To examine whether generic mental health workers can deliver effective behavioural activation as a step-three high-intensity intervention . METHOD A r and omised controlled trial ( IS RCT N27045243 ) comparing behavioural activation ( n=24 ) with treatment as usual ( n=23 ) in primary care . RESULTS Intention-to-treat analyses indicated a difference in favour of behavioural activation of -15.79 ( 95 % CI -24.55 to -7.02 ) on the Beck Depression Inventory-II and Work and Social Adjustment Scale ( mean difference -11.12 , 95 % CI -17.53 to -4.70 ) . CONCLUSIONS Effective behavioural activation appears suitable for delivery by generic mental health professionals without previous experience as therapists . Large-scale trial comparisons with an active comparator ( CBT ) are needed Although rumination is an important mediator of depressive symptoms , there is insufficient proof that an intervention that specifically targets rumination ameliorates the clinical condition of , depressed patients . This study investigates whether a time-limited cognitive behavioral intervention ( Competitive Memory Training , or COMET for depressive rumination ) is an effective treatment for depression and rumination . This intervention was tested in older adult depressed out patients . A total of 93 patients ( aged ≥ 65 years with major depression and suffering from rumination ) were treated in small groups according to the COMET protocol in addition to their regular treatment . Patients were r and omized to two treatment conditions : 7 weeks of COMET + treatment-as-usual ( TAU ) versus TAU only . COMET + TAU showed a significant improvement in depression and rumination compared with TAU alone . This study shows that the transdiagnostic COMET protocol for depressive rumination might also be successful in treating depression and rumination in older adults OBJECTIVE Although there is evidence for the efficacy of antidepressants and for some individual and group psychotherapy interventions for depressed older adults , a significant number of these do not respond to treatment . Authors assessed the benefits of augmenting medication with group psychotherapy . METHODS They r and omly assigned 34 ( largely chronically ) depressed individuals age 60 and older to receive 28 weeks of antidepressant medication plus clinical management , either alone ( MED ) or with the addition of dialectical behavior therapy skills-training and scheduled telephone coaching sessions ( MED+DBT ) . RESULTS Only MED+DBT showed significant decreases on mean self-rated depression scores , and both treatment groups demonstrated significant and roughly equivalent decreases on interviewer-rated depression scores . However , on interviewer-rated depression , 71 % of MED+DBT patients were in remission at post-treatment , in contrast to 47 % of MED patients . At a 6-month follow-up , 75 % of MED+DBT patients were in remission , compared with only 31 % of MED patients , a significant difference . Only patients receiving MED+DBT showed significant improvements from pre- to post-treatment on dependency and adaptive coping that are proposed to create vulnerability to depression . CONCLUSION Results from this pilot study suggest that DBT skills training and telephone coaching may offer promise to effectively augment the effects of antidepressant medication in depressed older adults Mixed treatment comparison ( MTC ) meta- analysis is a generalization of st and ard pairwise meta- analysis for A vs B trials , to data structures that include , for example , A vs B , B vs C , and A vs C trials . There are two roles for MTC : one is to strengthen inference concerning the relative efficacy of two treatments , by including both ' direct ' and ' indirect ' comparisons . The other is to facilitate simultaneous inference regarding all treatments , in order for example to select the best treatment . In this paper , we present a range of Bayesian hierarchical models using the Markov chain Monte Carlo software WinBUGS . These are multivariate r and om effects models that allow for variation in true treatment effects across trials . We consider models where the between-trials variance is homogeneous across treatment comparisons as well as heterogeneous variance models . We also compare models with fixed ( unconstrained ) baseline study effects with models with r and om baselines drawn from a common distribution . These models are applied to an illustrative data set and posterior parameter distributions are compared . We discuss model critique and model selection , illustrating the role of Bayesian deviance analysis , and node-based model criticism . The assumptions underlying the MTC models and their parameterization are also discussed BACKGROUND Psychotherapy 's equivalence paradox is that treatments tend to have equivalently positive outcomes despite non-equivalent theories and techniques . We replicated an earlier comparison of treatment approaches in a sample four times larger and restricted to primary -care mental health . METHOD Patients ( n=5613 ) who received cognitive-behavioural therapy ( CBT ) , person-centred therapy ( PCT ) or psychodynamic therapy ( PDT ) at one of 32 NHS primary -care services during a 3-year period ( 2002 - 2005 ) completed the Clinical Outcomes in Routine Evaluation - Outcome Measure ( CORE-OM ) at the beginning and end of treatment . Therapists indicated which approaches were used on an End of Therapy form . We compared outcomes of groups treated with CBT ( n=1045 ) , PCT ( n=1709 ) , or PDT ( n=261 ) only or with one of these plus one additional approach ( e.g. integrative , supportive , art ) , design ated CBT+1 ( n=1035 ) , PCT+1 ( n=1033 ) , or PDT+1 ( n=530 ) , respectively . RESULTS All six groups began treatment with equivalent CORE-OM scores , and all averaged marked improvement ( overall pre/post effect size=1.39 ) . Neither treatment approach nor degree of purity ( ' only ' v. ' + 1 ' ) had a statistically significant effect . Distributions of change scores were all similar . CONCLUSIONS Replicating the earlier results , the theoretically different approaches tended to have equivalent outcomes . Caution is warranted because of limited treatment specification , non-r and om assignment , incomplete data , and other issues . Insofar as these routine treatments appear effective for patients who complete them , those who fail to complete ( or to begin ) treatment deserve attention by research ers and policymakers BACKGROUND cognitive impairment is an important part of the diagnostic criteria for dementia . The Mini-Mental State Examination ( MMSE ) is recommended to test for cognitive impairment and to monitor medication response . OBJECTIVES we examined the prevalence of cognitive impairment in the UK and assessed associations with cognitive impairment . DESIGN cross-sectional survey as part of a cluster r and omised trial . SUBJECTS representative sample of people aged 75 years and over . METHODS all subjects had a detailed baseline health assessment including the MMSE . RESULTS a total of 15,051 subjects completed the assessment ( 71.9 % ) . Almost two-thirds of subjects were female ( 61.5 % ) and almost half were aged between 75 and 79 years ( 47.0 % ) . The prevalence of cognitive impairment was 18.3 % ( 95 % confidence intervals ( CI ) = 16.0 - 20.9 ) at a cut-off of 23/24 , and 3.3 % ( 95 % CI = 2.8 - 4.0 ) at 17/18 . Those with impairment ( MMSE 23/24 ) were significantly more likely to have hearing ( odds ratio ( OR ) 1.7 ) , vision ( OR 1.7 ) and urinary incontinence problems ( OR 1.3 ) , have two or more falls in the previous 6 months ( OR 1.4 ) , and report poorer health ( OR 1.9 ) . Almost half the participants lived alone ( n = 7,073 ; 47.0 % ) and of these almost one-fifth were impaired ( MMSE 23/24 ; 19.4 % ) . CONCLUSIONS there was a high prevalence of cognitive impairment . This representative sample demonstrates the potential burden of disease and service dem and s. It supports the need for a broader assessment of functioning as recommended by the National Service Framework for Older People , particularly in people with cognitive impairment OBJECTIVES To describe the patterns of self-reported medication use , including both prescription and non-prescription drugs , for older people in five areas in Engl and and Wales , and to identify the effects of socio-demographic features on medication use . DESIGN A cross-sectional survey on population r and om sample s of people aged 65 and over . The survey is a part of the screening interviews at the first stage of the Medical Research Council Cognitive Function and Ageing Study ( MRC CFAS ) carried out between 1991 and 1994 . The sample was stratified to provide equal numbers in the 65 - 74 years and 75 years and over age groups . SETTING Three urban ( Newcastle , Nottingham and Oxford ) and two rural ( Cambridgeshire and Gwynedd ) centres . Older people living in both the general community and institutions were included . PARTICIPANTS 12489 older people whose medication data were collected among the 13009 participants of the CFAS , of which the participation rate is 80 % . RESULTS Overall prevalence of medication use was 75 % ( 95 % confidence interval 74 - 76 % ) for people aged 65 - 74 and 84 % ( 83 - 85 % ) for people aged 75 and over , with a mean number of 2.03 ( st and ard deviation 1.95 ) and 2.47 ( 2.02 ) drugs reported per respondent in each group , respectively . Concurrent use of five or more drugs ( polypharmacy ) was found in 11 % ( 10 - 12 % ) of people in the 65 - 74 age group and in 15 % ( 14 - 16 % ) in the 75 and over age group . People aged 75 and over were more likely to be taking at least one drug than people aged 65 - 74 ( OR=1.69 , 1.54 - 1.85 ) , and women were more likely to be so compared with men ( OR=1.43 , 1.30 - 1.56 ) . Centre variation was found but none of the centres consistently showed higher or lower usage of medications across the major drug categories . People living in institutions were more likely to be taking gastrointestinal drugs , central nervous system drugs and experience polypharmacy . The use of respiratory and central nervous system drugs ( except hypnotics and anxiolytics ) increased in lower social class and decreased in people attending full-time education for 10 years or more . The use of haematology/dietetic drugs ( 85 % of which were vitamin and mineral preparations ) decreased in lower social class . CONCLUSION This study provides representative estimates of medication usage among older people in Engl and and Wales and identified associated factors and regional variations for medication use in a category-specific manner . The findings , suggesting the existence of centre variation and the association between type of accommodation , social class and medication use warrant further investigation OBJECTIVE Clinical guidelines recommend that antidepressant treatment should be continued for a minimum of 6 months following response in depression and anxiety disorders . However , adherence to antidepressants is low . This prospect i ve cohort study investigated the influence of patients ' antidepressant concerns , treatment preferences , and illness perceptions on adherence to antidepressants over a 6-month period . METHOD A cohort of 178 patients aged 18 to 74 years and newly issued with a prescription for antidepressants to treat any condition was followed up prospect ively at 5 primary care practice s in Southeast Engl and . Adherence was measured through self-report and prescription refill data . Patient perceptions were quantified using vali date d outcome measures , the Beliefs about Medicine Question naire and the Illness Perception Question naire , at 4 timepoints . Patient treatment preferences were recorded using a specially design ed question naire . Data collection took place between September 2000 and May 2002 . RESULTS Of 147 participants ( 83 % ) who completed the study , 19 % persisted with antidepressants in accordance with guideline recommendations throughout the 6-month period . Specific concern about antidepressant side effects ( OR = 3.30 , 95 % CI = 2.20 to 4.97 ) and general worry about taking antidepressants ( OR = 1.65 , 95 % CI = 1.13 to 2.40 ) were independent predictors of antidepressant nonuse . Preference for different treatment/uncertainty about preferred treatment was also a strong predictor ( OR = 3.82 , 95 % CI = 1.35 to 10.77 ) . However , illness perceptions were not associated with adherence . CONCLUSIONS Concerns about antidepressants and a mismatch between patients ' preferred and prescribed treatment act as significant barriers to sustained adherence . This study highlights the central role of the patient-physician partnership in exploring antidepressant concerns , working with treatment preferences , and providing supportive continued management . The findings may inform the development of interventions within primary care programs to enhance commitment to treatment for common mental disorders BACKGROUND Self-esteem is a major concern in mood disorders . Low self-esteem is a symptom of depressive disorders and is considered by some to be a predictor for relapse , whereas high self-esteem seems to buffer against depression . Recently , Competitive Memory Training ( COMET ) has shown to be effective for the enhancement of self-esteem in several psychopathological conditions . The current study assesses whether COMET is also an effective intervention for patients with depressive disorders . METHODS Sixty-one patients with depressive disorders who were already in therapy in an outpatient mental health institution were r and omly assigned to either eight group sessions of COMET in addition to their regular therapy ( COMET + therapy as usual [ TAU ] : the experimental group ) or to 8 weeks of ongoing regular therapy ( TAU only : the control group ) . These latter ( control ) patients received COMET after their TAU only period . All patients in both groups that completed COMET were contacted 3 and 6 months later to assess whether the effects of COMET had remained stable . RESULTS Compared to the patients who received TAU only , patients in the COMET + TAU condition showed significant improvement with large effect sizes on indices of self-esteem , depression , and depressive rumination . The therapeutic effects of COMET + TAU remained stable after 3 and 6 months on all outcome measures or improved even further . CONCLUSION COMET for low self-esteem seems to be an efficacious trans-diagnostic intervention that can relatively easily be added to the regular treatment of patients with depressive disorders OBJECTIVE The current study examined the efficacy of an early intervention based on acceptance and commitment therapy ( ACT ) for depressive symptomatology . The ACT intervention is aim ed at increasing the acceptance of negative thoughts and emotions and living a mindful and value-based life . METHOD Adults with mild to moderate depressive symptomatology were r and omly assigned to the ACT intervention ( n=49 ) or to a waiting list ( n=44 ) . The mean age of the participants was 49 years . The majority of the participants was female and of Dutch origin . All the participants completed measures before and after the intervention , as well as three months later at follow-up to assess depression ( CES-D ) , anxiety ( HADS-A ) , fatigue ( CIS ) , alcohol use and acceptance ( AAQ-II ) . RESULTS The ACT intervention led to statistically significant reduction in depressive symptomatology ( Cohen 's d=.60 ) . These reductions were maintained at the three-month follow-up . Also significant reductions in anxiety and fatigue were observed . Moreover , mediational analysis showed that the improvement of acceptance during the intervention mediated the effects of the intervention on depressive symptomatology at follow-up . CONCLUSION These findings suggest that an early intervention based on ACT , aim ed at increasing acceptance , is effective in reducing depressive symptomatology The brief behavioral activation treatment for depression ( BATD ) is a relatively uncomplicated , time-efficient , and cost-effective method for treating depression . Because of these features , BATD may represent a practical intervention within managed care-driven , inpatient psychiatric hospitals . Based on basic behavioral theory and empirical evidence supporting activation strategies , we design ed a treatment to increase systematic ally exposure to positive activities and thereby help to alleviate depressive affect . This study represents a pilot study that extends research on this treatment into the context of an inpatient psychiatric unit . Results demonstrate effectiveness and superiority of BATD as compared with the st and ard supportive treatment provided within the hospital . A large effect size was demonstrated , despite a limited sample size . The authors discuss the limitations of the study and future directions Antidepressant medication is considered the current st and ard for severe depression , and cognitive therapy is the most widely investigated psychosocial treatment for depression . However , not all patients want to take medication , and cognitive therapy has not demonstrated consistent efficacy across trials . Moreover , dismantling design s have suggested that behavioral components may account for the efficacy of cognitive therapy . The present study tested the efficacy of behavioral activation by comparing it with cognitive therapy and antidepressant medication in a r and omized placebo-controlled design in adults with major depressive disorder ( N = 241 ) . In addition , it examined the importance of initial severity as a moderator of treatment outcome . Among more severely depressed patients , behavioral activation was comparable to antidepressant medication , and both significantly outperformed cognitive therapy . The implication s of these findings for the evaluation of current treatment guidelines and dissemination are discussed OBJECTIVES To determine whether tango dancing is as effective as mindfulness meditation in reducing symptoms of psychological stress , anxiety and depression , and in promoting well-being . DESIGN This study employed analysis of covariance ( ANCOVA ) and multiple regression analysis . PARTICIPANTS Ninety-seven people with self-declared depression were r and omised into tango dance or mindfulness meditation classes , or to control/waiting-list . SETTING classes were conducted in a venue suitable for both activities in the metropolitan area of Sydney , Australia . INTERVENTIONS Participants completed six-week programmes ( 1½h/week of tango or meditation ) . The outcome measures were assessed at pre-test and post-test . MAIN OUTCOME MEASURES Depression , Anxiety and Stress Scale ; The Self Esteem Scale ; Satisfaction with Life Scale , and Mindful Attention Awareness Scale . RESULTS Sixty-six participants completed the program and were included in the statistical analysis . Depression levels were significantly reduced in the tango ( effect size d=0.50 , p=.010 ) , and meditation groups ( effect size d=0.54 , p=.025 ) , relative to waiting-list controls . Stress levels were significantly reduced only in the tango group ( effect size d=0.45 , p=.022 ) . Attending tango classes was a significant predictor for the increased levels of mindfulness R(2)=.10 , adjusted R(2)=.07 , F (2,59)=3.42 , p=.039 . CONCLUSION Mindfulness-meditation and tango dance could be effective complementary adjuncts for the treatment of depression and /or inclusion in stress management programmes . Subsequent trials are called to explore the therapeutic mechanisms involved |
12,811 | 10,796,135 | REVIEW ER 'S CONCLUSIONS Paternal cell immunization , third party donor leukocytes , trophoblast membranes , and IVIG provide no significant beneficial effect over placebo in preventing further miscarriages | BACKGROUND Immunologic aberrations might be the cause of recurrent early pregnancy loss in some women .
OBJECTIVES The objective of this review was to assess the effects of leukocyte immunisation or other immunologic treatments such as intravenous immune globulin ( IVIG ) on the live birth rate in women with previous unexplained recurrent miscarriages . | Twenty-two nulli- all primipara who had had previous repeated spontaneous abortions and who did not have anti-HLA antibodies for the partner , received immunological treatment consisting of a single transfusion of the partner 's lymphocytes in the third week of pregnancy , and giving natural progesterone supplements after the kinetic of Beta-HCG in the plasma had been assessed . The number of pregnancies which went to terme ( 94 % success ) was significantly better than those obtained in our first protocol which was to give one to three transfusions of the partner 's lymphocytes before the pregnancy started ( 58 % success rare after 24 treatments ) . Apart from obtaining much better results the second protocol made it possible to avoid giving a significant number of useless transfusions ( 22 % of pre-conceptual transfusions were not followed by a pregnancy at all ) Objective . To investigate whether active immunization with third party leukocytes improves pregnancy outcome in women with unexplained recurrent miscarriages Presented herein is a r and omized prospect i ve study performed to evaluate the efficacy of the addition of lymphocyte immunotherapy ( LI ) to progesterone ( P ) therapy ( LI/P ) for the prevention of spontaneous abortion ( SAB ) in primary aborters with a history of three SABs . The incidence of intrauterine pregnancies in four cycles was 23 of 35 ( 65.7 % ) patients for LI/P vs. 14 of 31 ( 45.1 % ) patients treated with progesterone alone . SABs occurred in 6 of 23 ( 26.0 % ) LI/P-treated patients compared to 8 of 14 ( 57.1 % ) given progesterone alone . The mean number of previous abortions in both groups was 3.9 . The mean age of the LI/P group was 34.1 vs. 33.6 years for the group treated with progesterone alone . These data could be interpreted to show that progesterone therapy and LI independently inhibit SAB or that LI/P acts synergistically to inhibit immune destruction . LI/P therapy was found to be more effective than progesterone therapy alone To eluci date the mechanisms that facilitate tolerance at the maternal-fetal interface , we are investigating the role of genes that are involved in peripheral self-tolerance in couples with idiopathic recurrent miscarriage . CTLA-4 is a negative regulator of T-cell proliferation and has been associated with human autoimmune disease . An AT(n ) polymorphism in the 3'-untranslated region ( UTR ) of the human gene results in AT stretches that vary in length from 16 to 46 bp . We hypothesized that long stretches of AT repeats would result in mRNA instability , and reduced fetal survival in humans . We examined the transmission of AT(n ) alleles in 60 couples with a history of > or = 3 unexplained spontaneous abortions to their 51liveborn children and 10 abortuses . The shorter allele was transmitted from heterozygous mothers to 26 of 35 liveborn children ( chi2 = 8.3 , P = 0.0040 ) and to three of nine aborted fetuses ( chi2 = 1.0 , P = 0.317 ) . The shorter allele was transmitted from heterozygous fathers to 15 of 32 liveborn children ( chi2 = 0.12 , P=0.726 ) and to five of eight aborted fetuses ( chi2 = 0.5 , P = 0.480 ) . Furthermore , liveborn fetuses who inherited smaller alleles were more likely to represent the first successful pregnancy than liveborn fetuses who inherited larger maternal alleles ( Pexact = 0.044 ) and fetuses of first pregnancies that inherited the smaller allele were significantly more likely to survive to term ( Pexact = 0.0086 ) . The preferential transmission of maternally-inherited shorter alleles to liveborn children , but r and om transmission of paternally-inherited alleles , suggests that CTLA-4 may be imprinted in humans and that this gene may play a role in inducing or maintaining tolerance at the maternal-fetal interface The aim of this study was to evaluate the therapeutic efficacy of intravenous immunoglobulin ( IVIG ) in the prevention of recurrent spontaneous abortion ( RSA ) . In a double-blind , r and omized , placebo-controlled study , 41 women with a history of unexplained recurrent spontaneous abortion were treated with IVIG or saline infusions during pregnancy . The birth of a child was considered a successful outcome . The overall success rate was 77 % in the IVIG group compared with 79 % in the placebo group . For women with primary RSA the success rates were 82 ( IVIG ) and 89 % ( placebo ) , and for women with secondary RSA the rates were 73 ( IVIG ) and 70 % ( placebo ) . We found no statistically significant difference in treatment results between IVIG and placebo It is still unclear whether i.v . immunoglobulins ( Ig ) can facilitate the reproductive prognosis of women who have suffered recurrent pregnancy loss . We report the results of a multicentre placebo-controlled study on the effect of Ig administration on pregnancy outcome in 46 women who had suffered at least three recurrent miscarriages . All were screened to exclude chromosomal or Müllerian abnormalities , the presence of antinuclear antibodies , lupus anticoagulant ( LA ) or elevated titres of anticardiolipin antibodies which may have revealed an underlying autoimmune problem . To avoid a selection bias towards ongoing pregnancies , i.v . Ig or placebo were administered between weeks 5 and 7 of gestation for 2 consecutive days as soon as each woman knew she was pregnant and before embryonic heart activity could be detected . A further infusion was administered at week 8 when ultrasonography confirmed an ongoing embryonic development . In all , 68 % of the women who received Ig went to term versus 79 % of those who received a placebo ( not significant ) , with no significant differences in the pregnancy course or the perinatal outcome . These results suggest either that women with recurrent miscarriages who have no recognized cause of pregnancy loss have a good reproductive prognosis without any treatment or that the emotional care associated with the administration of a placebo can indirectly facilitate the progression of pregnancy The Recurrent Miscarriage ( REMIS ) study is a double-blind , multicenter , r and omized clinical trial design ed to evaluate the efficacy of immunization with paternal leukocytes in the prevention of miscarriages in women who have had three or more unexplained pregnancy losses . Women entering the study are immunized with their husb and 's leukocytes or with a saline control before they become pregnant . After becoming pregnant , they receive weekly ultrasound examinations and psychological support during the first trimester and are followed until a successful delivery or a miscarriage occurs . The primary analysis for the study will be an intent-to-treat analysis in which we shall compare the proportion of successes in the two groups , defining a " success " as a pregnancy achieved within 12 months of r and omization that results in a viable offspring . We shall count both miscarriages and nonpregnancies as failures , owing to the possibility of very early losses prior to the detection of pregnancy . In a secondary analysis , we shall exclude women who do not become pregnant within the alloted 12 month period . We compared the test size and power of these two approaches under various configurations for the true rates of nonpregnancy , miscarriage , and delivery in the two groups . Although the analysis excluding nonpregnant women achieves greater power for alternatives in which pregnancy rates are equal and live birth rates higher in the treated group , the rejection rate is not adequately controlled when pregnancy rates differ but live birth rates are unaffected by treatment . It can also lead to a reduction in power if the treatment prevents early as well as later losses . We conclude that the intent-to-treat analysis should remain the primary analysis for the trial ABSTRACT : The efficacy of immunotherapy for the treatment of recurrent spontaneous abortions was tested in patients selected from the same ethnically homogeneous population of Chinese in Taiwan in whom the immunogenetics of gestational trophoblastic tumors and of recurrent spontaneous abortion had been studied . The patients , who included both primary and secondary aborters , were r and omly assigned to three groups : those who were immunized with their own lymphocytes ( controls ) ( 49 ) ; those who were immunized with their husb and s ' lymphocytes ( 39 ) ; and those who were immunized with third party lymphocytes ( 11 ) . The data were analyzed individually for the primary and secondary aborters and collectively for both groups combined . The number of babies born , the number of current pregnancies , and the number of recurrent abortions were not statistically significantly different between the control and the immunized groups , and a similar small number of congenital abnormalities ( 4–9 % ) occurred in both the control and immunized groups . The increase in the blocking effect for the mixed lymphocyte reaction was not related to the success of the postimmunization pregnancies . Thus , this study does not show any significant improvement in the rate of livebirths in women immunized with their husb and s ' lymphocytes or with third party lymphocytes compared to that in a placebo‐controlled group of women BACKGROUND Couples with unexplained recurrent miscarriage may have an alloimmune abnormality that prevents the mother from developing immune responses essential for the survival of the genetically foreign conceptus . Immunisation with paternal mononuclear cells is used as a treatment for such alloimmune-mediated pregnancy losses . However , the published results on this treatment are conflicting . In this study ( the Recurrent Miscarriage [ REMIS ] Study ) , we investigated whether paternal mononuclear cell immunisation improves the rate of successful pregnancies . METHODS Women who had had three or more spontaneous abortions of unknown cause were enrolled in a double-blind , multicentre , r and omised clinical trial . 91 were assigned immunisation with paternal mononuclear cells ( treatment ) and 92 immunisation with sterile saline ( control ) . The primary outcomes were the inability to achieve pregnancy within 12 months of r and omisation , or a pregnancy which terminated before 28 weeks of gestation ( failure ) ; and pregnancy of 28 or more weeks of gestation ( success ) . Two analyses were done : one included all women ( intention to treat ) , and the other included only those who became pregnant . FINDINGS Two women in each group received no treatment , and eight ( three treatment , five control ) were censored after an interim analysis . In the analysis of all r and omised women who completed the trial , the success rate was 31/86 ( 36 % ) in the treatment group and 41/85 ( 48 % ) in the control group ( odds ratio 0.60 [ 95 % CI 0.33 - 1.12 ] , p=0.108 ) . In the analysis of pregnant women only , the corresponding success rates were 31/68 ( 46 % ) and 41/63 ( 65 % ; odds ratio 0.45 [ 0.22 - 0.91 ] , p=0.026 ) . The results were unchanged after adjustment for maternal age , number of previous miscarriages , and whether or not the couple had had a previous viable pregnancy . Similar results were obtained in a subgroup analysis of 133 couples with no previous livebirth . INTERPRETATION Immunisation with paternal mononuclear cells does not improve pregnancy outcome in women with unexplained recurrent miscarriage . This therapy should not be offered as a treatment for pregnancy loss PROBLEM : The efficacy of intravenous immunoglobulin ( IVIG ) for treatment of unexplained recurrent spontaneous abortion was assessed in a prospect i ve , r and omized , double‐blinded , and placebo‐controlled study PROBLEM : Recurrent spontaneous abortion ( RSA ) is the cause of childlessness in 2–5 % of reproducing couples . Immunological mechanisms have been proposed as an etiology in some cases of RSA . Various forms of immunotherapy have been attempted in individuals thought to have an immunologic mechanism associated with RSA . Intravenous immunoglobulin ( IVIG ) has been used in a pilot study to successfully treat women with RSA We conducted a r and omized trial comparing expectant management versus immunotherapy with paternal leukocytes to improve obstetric outcome in women with unexplained recurrent abortion . Eligible for the study were women with unexplained recurrent abortion ( three or more miscarriages and no live birth ) , negative findings of immunological screening and no inhibition of the mixed lymphocyte culture . These women were seen for the first time between October 1988 and March 1991 in a network of obstetric departments in Northern Italy . Subjects positive for HLA DR3 or with a partner positive for hepatitis virus B antigen were not eligible . A total of 44 women entered the study . Patients were r and omly allocated to immunotherapy ( 22 women ) or expectant management ( 22 women ) . Women allocated to immunotherapy were given 200 x 10(6 ) purified paternal lymphocytes before pregnancy . Median follow-up was 24 months ( range 10 - 39 ) in the immunotherapy group and 25 months ( range 11 - 38 ) in the expectant management group . Out of the 22 women r and omized to immunotherapy , 16 became pregnant and the corresponding value was 14 in the expectant management group . Spontaneous abortion occurred in six out of the 16 pregnancies observed in the treated women . Among the 14 pregnancies observed in the expectant management group , two aborted and one late fetal death occurred . The cumulative proportions of women who became pregnant over 4 years were 37 and 45 % in the immunotherapy and expectant management groups respectively ; this difference was not significant . No adverse effect was observed in treated women PROBLEM : Efficacy of immunotherapy for treatment of recurrent spontaneous abortion ( SA ) has been controversial . The low treatment effect of white blood cell immunization lead to investigations of alternative treatments including intravenous ( IV ) immunoglobulin ( Ig ) . To evaluate the efficacy of IVIg for treatment of recurrent SA , a prospect i ve , r and omized , double blinded , placebo‐controlled trial was performed ABSTRACT : A paired sequential trial was undertaken to establish whether paternal mononuclear cells improved the prognosis in couples with recurrent abortions . For this purpose , 107‐108 cells obtained from the blood of partners were injected intravenously , subcutaneously , and intra‐dermally into women who had had three or more consecutive miscarriages with the same partner . Control women were given normal saline , injected in the same manner . The result of the sequential analysis showed that there was no significant beneficial effect of the cells compared to control . The overall success rate was 70 % ( 32/46 couples ) . The success rate in patients given cells was 62 % ( 13/21 ) , while in those given saline it was 76 % ( 19/25 ) . While the overall success rate in this study compares with a number of other studies , we find an equally high success rate with non‐immunized patients . We conclude that the value of immunization for the prevention of recurrent miscarriage has not been established In a paired sequential double-blind trial of immunological treatment of recurrent spontaneous abortion successful outcome of the next pregnancy was significantly more common in women injected with purified lymphocytes prepared from their husb and s ' blood than in those injected with their own lymphocytes . 17 of 22 women given paternal cells had successful pregnancies , compared with 10 of 27 given their own cells We report a family ascertained for molecular diagnosis of muscular dystrophy in a young girl , in which preferential activation ( > or = 95 % of cells ) of the paternal X chromosome was seen in both the prob and and her mother . To determine the molecular basis for skewed X inactivation , we studied X-inactivation patterns in peripheral blood and /or oral mucosal cells from 50 members of this family and from a cohort of normal females . We found excellent concordance between X-inactivation patterns in blood and oral mucosal cell nuclei in all females . Of the 50 female pedigree members studied , 16 showed preferential use ( > or = 95 % cells ) of the paternal X chromosome ; none of 62 r and omly selected females showed similarly skewed X inactivation was maternally inherited in this family . A linkage study using the molecular trait of skewed X inactivation as the scored phenotype localized this trait to Xq28 ( DXS1108 ; maximum LOD score [ Zmax ] = 4.34 , recombination fraction [ theta ] = 0 ) . Both genotyping of additional markers and FISH of a YAC probe in Xq28 showed a deletion spanning from intron 22 of the factor VIII gene to DXS115 - 3 . This deletion completely cosegregated with the trait ( Zmax = 6.92 , theta = 0 ) . Comparison of clinical findings between affected and unaffected females in the 50-member pedigree showed a statistically significant increase in spontaneous-abortion rate in the females carrying the trait ( P < .02 ) . To our knowledge , this is the first gene-mapping study of abnormalities of X-inactivation patterns and is the first association of a specific locus for recurrent spontaneous abortion in a cytogenetically normal family . The involvement of this locus in cell lethality , cell-growth disadvantage , developmental abnormalities , or the X-inactivation process is discussed The aim of this trial was to investigate whether infusions of i.v . immunoglobulins ( Ig ) to women with secondary recurrent spontaneous abortions and recurrent second trimester spontaneous abortions can increase the rate of successful pregnancy . In a prospect i ve , double-blind , placebo-controlled trial , infusions of i.v . Ig ( Nordimmun ) or placebo were given during pregnancy to 34 women with a history of either unexplained recurrent spontaneous abortion subsequent to a birth or including at least one second trimester miscarriage . The success rate was 52.9 % in the i.v . Ig group compared with 29.4 % in the placebo group ( not significantly different , therapeutic gain 23.5 % , 95 % confidence interval -8.6 to 55.7 % ) . No changes in autoantibody concentrations or major lymphocyte subsets were induced by i.v . Ig treatment . In conclusion , an expected 55 % therapeutic gain of i.v . Ig in recurrent spontaneous abortion could not be confirmed using the treatment regimen tested . However , to determine whether the trend of therapeutic gain of i.v . Ig in these women may be statistically significant , a larger trial is in progress OBJECTIVE To describe the ultrasonographic findings of pregnancies that terminated in repeat abortion in women participating in an ongoing r and omized placebo-controlled clinical trial evaluating the efficacy of intravenous ( IV ) immunoglobulin ( Ig ) in the treatment of recurrent spontaneous abortion ( SA ) . DESIGN A prospect i ve descriptive study of ultrasonographic findings of pregnancies from 27 women experiencing repeated recurrent SAs after entry into a clinical trial . SETTING Clinical practice at the Genetics & IVF Institute in Fairfax , Virginia . PATIENTS Women experiencing two or more consecutive recurrent SAs received either 500 mg/kg per mo IV Ig or placebo ( albumin ) . To date 90 women have been enrolled in the clinical trial and 52 have achieved pregnancy . The outcome of the 52 pregnancies include 16 deliveries , 9 ongoing pregnancies , and 27 losses . INTERVENTIONS Ultrasonographic examinations performed in 27 women experiencing pregnancy loss are the subject of this study . MAIN OUTCOME MEASURES The frequency of ultrasonographic findings of empty gestation sac ( blighted ovum ) and intrauterine fetal demise ( IUFD ) is compared between patients receiving IV Ig and placebo . RESULTS Ultrasonographic findings of the 27 pregnancies losses included 11 blighted ova and 16 IUFDs . Of 11 blighted ova , 8 ( 73 % ) were in women receiving IV Ig and 3 ( 27 % ) were receiving placebo . Sixteen IUFDs were observed : 3 ( 19 % ) in women receiving IV Ig and 13 ( 81 % ) in women receiving placebo . Of 11 pregnancy losses occurring in women receiving IV Ig , 8 ( 73 % ) were blighted ova , 3 ( 27 % ) were IUFDs . Sixteen pregnancy losses occurred in women receiving placebo : 3 ( 19 % ) were blighted ova and 13 ( 81 % ) were IUFDs . The differences in frequency of blighted ova between IV Ig- and placebo-treated women was significant . CONCLUSION IV Ig is not effective in preventing blighted ova and may be effective in preventing IUFDs BACKGROUND Previous trials of intravenous immunoglobulin ( IvIg ) treatment of women with recurrent miscarriage ( RM ) have provided diverging results . This may be due to different inclusion criteria and suboptimal treatment protocol s in some trials . METHODS According to a computer-generated list , 58 women with at least four unexplained miscarriages were r and omly assigned to receive infusions of high doses of IvIg or placebo starting as soon as the pregnancy test was positive . RESULTS In the intention-to-treat analysis , a 45 % live birth rate was found in both allocation groups . In patients with secondary RM , 50 % in the treatment group and 23 % in the placebo group had successful pregnancies ( P = not significant ) . When data from the present and a previous placebo-controlled trial of the same treatment were combined , 15/26 ( 58 % ) of the patients with secondary RM in the treatment group versus 6/26 ( 24 % ) in the placebo group had successful outcomes ( P < 0.02 ) . Only 7 % of the karyotyped abortuses were abnormal . CONCLUSIONS IvIg may improve pregnancy outcome in patients with secondary RM . A new placebo-controlled trial focusing on this subgroup should be conducted to confirm the results There is no immunological test for the prospect i ve identification of alloimmune causes of miscarriage . We investigated whether activity of natural killer cells was predictive of subsequent abortion in women who had had unexplained recurrent abortions and had received no treatment . 24 women with high preconceptional NK activity , defined as mean plus 1 SD of NK activity of 47 controls , had a significantly higher abortion rate in the next pregnancy than 44 women with normal levels of NK activity ( 71 vs 20 % ; relative risk 3.5 ; 95 % CI 1.8 - 6.5 ) . The preconceptional evaluation of NK activity in women with recurrent miscarriages may thus be predictive of the risk of pregnancy loss at the next conception |
12,812 | 15,846,745 | Data regarding quality of life and economic outcomes are difficult to interpret , and for both these highly marketed new drugs we know very little from evaluative studies regarding service outcomes , general functioning and behaviour , engagement with services and treatment satisfaction .
There is little to differentiate between risperidone and olanzapine except on the issue of adverse effects and both these drugs have unpleasant adverse effects .
Risperidone is particularly associated with movement disorders and sexual dysfunction .
Olanzapine can cause considerable rapid weight gain . | BACKGROUND Antipsychotic medication is a mainstay of treatment for schizophrenia and risperidone and olanzapine are the most popular treatment choice of the new generation drugs .
OBJECTIVES To determine the clinical effects , safety and cost effectiveness of risperidone compared with olanzapine for treating schizophrenia . | Background Atypical antipsychotic drugs , in clinical doses , occupy 5-HT2 receptors near saturation , while D2 dopamine receptors , assessed usually in striatum by SPECT or PET methods , are occupied to different degrees . We hypothesized that these differences in D2 receptor occupancies may also be evaluated by a neuroendocrine approach , namely by measuring the plasma prolactin responses to i. m. administered haloperidol , since the expected elevations depend mainly on the free remaining D2 receptors in the tuberoinfundibular tract . Methods We measured the plasma prolactin levels at 0 , 30 , 60 , 90 , and 120 minutes after administration of 5 mg haloperidol i. m. in six groups of male patients with schizophrenia : a ) 33 patients in a drug-free state , b ) 15 patients on treatment with clozapine ( range 200–600 mg/day ) , c ) 15 patients on olanzapine ( 10–30 mg/day ) , d ) 14 patients on risperidone ( 8–16 mg/day ) , e ) 23 patients on haloperidol ( 10–40 mg/day ) , f ) 14 patients on sulpiride ( 600–1600 mg/day ) . Data were also obtained from a group of 14 healthy male control subjects . The differences in baseline prolactin levels and in the responses to acute haloperidol of the seven groups were compared . Results The baseline prolactin levels did not differ significantly in the groups of controls ( 8.3±3.8 ng/ml ) , drug-free patients ( 8.0±3.6 ) and patients treated with clozapine ( 7.7±3.8 ) , they were moderately elevated in patients treated with olanzapine ( 16.8±8.9 ) , elevated in patients on haloperidol ( 34.4±17.3 ) , and they were even higher in the groups of patients treated with risperidone ( 54.9±22.4 ) or sulpiride ( 58.8±27.0 ) . All groups of patients gave attenuated prolactin responses to i. m. haloperidol compared to healthy controls . During treatment with haloperidol , risperidone , or sulpiride , no significant prolactin increases after i. m. haloperidol were observed . The group treated with olanzapine gave significant prolactin increases , which were lower than those obtained in the group of patients treated with clozapine , who gave responses similar to that of the drug-free patients . Conclusions Plasma prolactin levels and responses to i. m. haloperidol of patients on treatment with antipsychotic drugs , reflect the prolactin release potencies of the drugs , which are related , but not restricted , to their affinities to D2 dopamine receptors . According to the prolactin baseline levels and responses to i. m. haloperidol , the drugs of this study can be categorized for their potency to the pituitary dopamine system that controls prolactin release , as follows : sulpiride > risperidone > haloperidol > olanzapine > clozapine . This categorization is similar to that obtained by binding studies in striatal D2 dopamine receptors using brain imaging techniques BACKGROUND The purpose of this investigation was to test the efficacy of novel antipsychotic medications in the treatment of cognitive impairment in early phase schizophrenia . METHODS Sixty-five patients in this multicenter double-blind study were r and omly assigned to olanzapine ( 5 - 20 mg ) , risperidone ( 4 - 10 mg ) , or haloperidol ( 5 - 20 mg ) . St and ard measures of clinical and motor syndromes were administered , as well as a comprehensive battery of tests to assess ( 1 ) motor skills , ( 2 ) attention span , ( 3 ) verbal fluency and reasoning , ( 4 ) nonverbal fluency and construction , ( 5 ) executive skills , and ( 6 ) immediate recall at baseline and after 6 , 30 , and 54 weeks of treatment . RESULTS The general cognitive index derived from the 6 domain scores revealed a significantly greater benefit from treatment with olanzapine relative to haloperidol and olanzapine relative to risperidone , but no significant difference was shown between risperidone and haloperidol . The improvement related to olanzapine was apparent after 6 weeks and enhanced after 30 and 54 weeks of treatment . Exploratory within-group analyses of the 6 cognitive domains after a conservative Bonferroni adjustment revealed a significant improvement with olanzapine only on the immediate recall domain , and similar analyses of the 17 individual tests revealed a significant improvement with olanzapine only on the Hooper Visual Organization Test . CONCLUSIONS These data suggest that olanzapine has some superior cognitive benefits relative to haloperidol and risperidone . A larger sample replication study is necessary to confirm and generalize the observations of this study and begin evaluation of the implication s of this change to cerebral function and quality of life for people with schizophrenia Subjective and objective evaluation of pharmacological treatment was made in 105 schizophrenic in- patients . PANSS and Calgary scale as well as Van Putten scale were used . Fifty-four percent of subjects received classic neuroleptics and 46%--new atypical drugs for an average period of 8 weeks . The severity of schizophrenic symptoms during treatment as well as subjective evaluation of first effects of the drug did not differ among subjects treated with classic or atypical drugs . Depressive symptoms decreased significantly during treatment with atypicals but not with classic drugs . Also a significant decrease of depression was found under olanzapine treatment . The severity of neuroleptic-induced side-effects did not differ in both groups . Neurological side effects were more prominent in subjects after 4 weeks of therapy with risperidone , in comparison to patients receiving olanzapine . Forty-seven per-cent of patients showed a dysphoric reaction to the first dose of medication . After treatment with atypical drugs , better subjective evaluation of pharmacotherapy correlated with less severe general and depressive schizophrenia symptoms . Patients ' better evaluation of olanzapine treatment correlated with less severe schizophrenic general symptomatology . The subjective evaluation of treatment was better in patients with less severe neurological side-effects of atypical drugs ( including olanzapine but not risperidone ) and less severe autonomic side-effects of classic drugs . The evaluation of pharmacotherapy made by patients ' family members did not correlate with subjects ' opinions after distribution of the first dose of the drugs , but correlated significantly with patients ' opinion after 8-weeks of treatment . The treatment received by the patients was judged better by the family members if less severe neurological side-effects were present Improved drug therapy for schizophrenia may represent the best strategy for reducing the costs of schizophrenia and the recurrent chronic course of the disease . Olanzapine and risperidone are atypical antipsychotic agents developed to meet this need . We report a multicenter , double-blind , parallel , 30-week study design ed to compare the efficacy , safety , and associated re source use for olanzapine and risperidone in Australia and New Zeal and . The study sample consisted of 65 patients who met DSM-IV criteria for schizophrenia , schizoaffective disorder , or schizophreniform disorder . Olanzapine-treated patients showed a significantly greater reduction in Positive and Negative Syndrome Scale ( PANSS ) total , Brief Psychiatric Rating Scale ( BPRS ) total , and PANSS General Psychopathology scores at endpoint compared to the risperidone-treated patients . Response rates through 30 weeks showed a significantly greater proportion of olanzapine-treated patients had achieved a 20 % or greater improvement in their PANSS total score compared to risperidone-treated patients . Olanzapine and risperidone were equivalent in their improvement of PANSS positive and negative scores and Clinical Global Impression-Severity of Illness scale ( CGI-S ) at endpoint . Using generic and disease-specific measures of quality of life , olanzapine-treated patients showed significant within-group improvement in most measures , and significant differences were observed in favor of olanzapine over risperidone in Quality of Life Scale ( QLS ) Intrapsychic Foundation and Medical Outcomes Study Short Form 36-item instrument ( SF-36 ) Role Functioning Limitations -Emotional subscale scores . Despite the relatively small sample size , our study suggests that olanzapine has a superior risk : benefit profile compared to risperidone OBJECTIVE Newer antipsychotic drugs have shown promise in ameliorating neurocognitive deficits in patients with schizophrenia , but few studies have compared newer antipsychotic drugs with both clozapine and conventional agents , particularly in patients who have had suboptimal response to prior treatments . METHOD The authors examined the effects of clozapine , olanzapine , risperidone , and haloperidol on 16 measures of neurocognitive functioning in a double-blind , 14-week trial involving 101 patients . A global score was computed along with scores in four neurocognitive domains : memory , attention , motor function , and general executive and perceptual organization . RESULTS Global neurocognitive function improved with olanzapine and risperidone treatment , and these improvements were superior to those seen with haloperidol . Patients treated with olanzapine exhibited improvement in the general and attention domains but not more than that observed with other treatments . Patients treated with risperidone exhibited improvement in memory that was superior to that of both clozapine and haloperidol . Clozapine yielded improvement in motor function but not more than in other groups . Average effect sizes for change were in the small to medium range . More than half of the patients treated with olanzapine and risperidone experienced " clinical ly significant " improvement ( changes in score of at least one-half st and ard deviation relative to baseline ) . These findings did not appear to be mediated by changes in symptoms , side effects , or blood levels of medications . CONCLUSIONS Patients with a history of suboptimal response to conventional treatments may show cognitive benefits from newer antipsychotic drugs , and there may be differences between atypical antipsychotic drugs in their patterns of cognitive effects OBJECTIVE The authors sought to compare the effects of olanzapine , quetiapine , and risperidone on neurocognitive function in patients with early psychosis . METHOD In a 52-week double-blind , multicenter study , 400 patients early in the course of psychotic illness ( < 5 years ) were r and omly assigned to treatment with olanzapine ( 2.5 - 20 mg/day ) , quetiapine ( 100 - 800 mg/day ) , or risperidone ( 0.5 - 4 mg/day ) . The mean modal daily dose was 11.7 mg ( SD=5.3 ) for olanzapine , 506 mg ( SD=215 ) for quetiapine , and 2.4 mg ( SD=1.0 ) for risperidone . A total of 224 patients completed neurocognitive assessment s at baseline and at 12 weeks , and 81 patients also completed them at 52 weeks . Neurocognitive composite scores were calculated from the neurocognitive battery used in the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) and from the Brief Assessment of Cognition in Schizophrenia . RESULTS At week 12 , there was significant improvement in neurocognition for each treatment ( p<0.01 ) , but no significant overall difference between treatments . Composite z score improvements on the CATIE neurocognitive battery were 0.17 for olanzapine , 0.33 for quetiapine , and 0.32 for risperidone . Composite z score improvements on the Brief Assessment of Cognition in Schizophrenia were 0.19 for olanzapine , 0.34 for quetiapine , and 0.22 for risperidone . Statistically significant relationships between improvements in neurocognition and functional outcome were observed at weeks 12 and 52 . CONCLUSIONS Olanzapine , quetiapine , and risperidone all produced significant improvements in neurocognition in early-psychosis patients . Although cognitive improvements were modest , their clinical importance was suggested by relationships with improvements in functional outcome Olanzapine and risperidone , both second-generation antipsychotic agents , represent two different pharmacologic strategies . Although they share some in vitro properties , they differ by virtue of their chemical structure , spectrum of receptor binding affinities , animal neuropharmacology , pharmacokinetics , and in vivo neuroimaging profile . Based on such differences , it was hypothesized that the two compounds would show distinct safety and /or efficacy characteristics . To test this hypothesis , an international , multicenter , double-blind , parallel-group , 28-week prospect i ve study was conducted with 339 patients who met DSM-IV criteria for schizophrenia , schizophreniform disorder , or schizoaffective disorder . Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms . However , olanzapine demonstrated significantly greater efficacy in negative symptoms ( Scale for Assessment of Negative Symptoms summary score ) , as well as overall response rate ( > or = 40 % decrease in the Positive and Negative Syndrome Scale total score ) . Furthermore , a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves . The incidence of extrapyramidal side effects , hyperprolactinemia , and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients . In addition , statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts . Thus , the differential pre clinical profiles of these two drugs were also evident in a controlled , clinical investigation . Olanzapine seemed to have a risk-versus-benefit advantage OBJECTIVE The authors investigated the clinical effects of D-cycloserine when added to treatment with conventional neuroleptics , olanzapine , or risperidone for treatment-resistant schizophrenia . METHOD Twenty-four patients participated in a double-blind , placebo-controlled , 6-week crossover trial with D-cycloserine , 50 mg/day , added to their fixed dose of antipsychotic medication . Clinical ratings were performed every 2 weeks . RESULTS D-Cycloserine treatment was well tolerated and result ed in a significant reduction in negative symptoms ( mean=15 % ) . The degree of improvement did not differ between patients treated with conventional neuroleptics and those treated with olanzapine or risperidone . CONCLUSIONS These data support the efficacy of the addition of 50 mg/day of D-cycloserine to treatment with conventional neuroleptics and suggest that therapeutic benefits may also be attained when D-cycloserine is added to olanzapine or risperidone OBJECTIVE The purpose of this study was to compare the efficacy of olanzapine with that of chlorpromazine plus benztropine in patients with treatment-resistant schizophrenia . METHOD One hundred three previously treatment-resistant patients with schizophrenia diagnosed according to the DSM-III-R criteria were given a prospect i ve 6-week trial of 10 - 40 mg/day of haloperidol . Eighty-four of them failed to respond to that trial and agreed to be r and omly assigned to an 8-week fixed-dose trial of either 25 mg/day of olanzapine alone or 1200 mg/day of chlorpromazine plus 4 mg/day of benztropine mesylate . RESULTS Fifty-nine ( 70 % ) of the 84 subjects completed the trial . The primary outcome measures were Brief Psychiatric Rating Scale total score and positive symptom score , Scale for the Assessment of Negative Symptoms global score , and Clinical Global Impression score . An analysis of variance for the subjects who completed the study showed no difference in efficacy between the two drugs . Seven percent of the olanzapine-treated patients responded according to a priori criteria ; no chlorpromazine-treated patients responded . The olanzapine-treated patients had fewer motor and cardiovascular side effects than the chlorpromazine-treated patients . Extrapyramidal symptoms and akathisia were similar in the two groups , although no antiparkinsonian drugs were used in the olanzapine group . CONCLUSIONS Olanzapine and chlorpromazine showed similar efficacy , and the total amount of improvement with either drug was modest . Olanzapine-treated patients had fewer side effects than chlorpromazine-treated patients To assess the cost and effectiveness of risperidone , olanzapine , and conventional antipsychotic medications under " usual practice " conditions in a large , public mental health system , 108 persons diagnosed with schizophrenia or schizoaffective disorder were r and omly assigned to one of these three medication groups and followed prospect ively over a 12-month period using st and ard instruments and procedures . Psychiatric medication costs increased more over time in both the olanzapine and risperidone groups than in the conventional medication group . Compliance with the prescribed medication was higher in the olanzapine group than in the conventional group . No differential effects by medication group were evident in this sample on the symptoms of schizophrenia , side effects , psychosocial functioning , time to discharge for index hospitalization , survival to initial rehospitalization , or client satisfaction with services . These results extend findings from previous efficacy and naturalistic studies in several ways but are limited chiefly by the small number of subjects who completed 6 to 12 months of the clinical trial , and the result ing power to detect differences in the statistical analyses The main objective of this study was to compare 1-year outcome on symptoms , extrapyramidal side effects ( EPS ) , positive and negative symptoms , and domains of cognition in first episode psychosis ( FEP ) patients . Drug-naive FEP patients , who were similar on a number of characteristics likely to affect outcome , were treated with only one antipsychotic ( risperidone or olanzapine ) for at least 1 year and compared at baseline and after 1 year of treatment . Differences in outcome were assessed using an analysis of co-variance with change scores between initial assessment and after 1 year of treatment on levels of psychotic , disorganization and psychomotor poverty symptoms , EPS ( parkinsonism , akathesia and dyskineisa ) and domains of cognition as the dependent variable , respective baseline scores as covariates , and drug group as the independent variable . While patients in both groups showed substantial improvement , there were no significant differences in the magnitude of change in reality distortion , disorganization and psychomotor poverty symptoms . Trends in change in EPS favouring olanzapine and on some domains of cognition ( processing speed and executive functions ) favouring risperidone failed to reach statistical significance . The failure to confirm previous cl aims of greater improvement on either risperidone or olanzapine in patients with a first episode of psychosis may be the result of method ological bias introduced by unequal dosing between the two drugs or the use of chronically ill and treatment-refractory patients in previous studies The authors estimated components of variance and intraclass correlation coefficients ( ICCs ) to aid in the design of complex surveys and community intervention studies by analyzing data from the Health Survey for Engl and 1994 . This cross-sectional survey of English adults included data on a range of lifestyle risk factors and health outcomes . For the survey , households were sample d in 720 postal code sectors nested within 177 district health authorities and 14 regional health authorities . Study subjects were adults aged 16 years or more . ICCs and components of variance were estimated from a nested r and om-effects analysis of variance . Results are presented at the district health authority , postal code sector , and household levels . Between-cluster variation was evident at each level of clustering . In these data , ICCs were inversely related to cluster size , but design effects could be substantial when the cluster size was large . Most ICCs were below 0.01 at the district health authority level , and they were mostly below 0.05 at the postal code sector level . At the household level , many ICCs were in the range of 0.0 - 0.3 . These data may provide useful information for the design of epidemiologic studies in which the units sample d or allocated range in size from households to large administrative areas BACKGROUND There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval ( QTc ) representing a delay in ventricular repolarization . QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias , especially torsade de pointes , and therefore , sudden cardiac death . METHOD Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled , r and omized clinical trials ( N = 2,700 ) were analyzed . These analyses were conducted to characterize any change in QTc temporally associated with olanzapine , compared with placebo , haloperidol , and risperidone , in acutely psychotic patients ( DSM-III-R and DSM-IV ) and to characterize variability and temporal course of the QTc in this patient population . Changes from baseline to minimum and maximum QTc were tested for significance , and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators . The possibility of a linear relationship between dose of olanzapine and mean change in QTc , as well as incidence of treatment-emergent prolongation of QTc ( change from < 430 msec at baseline to > or = 430 msec at endpoint ) , was tested . RESULTS The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or = 450 msec at baseline . CONCLUSION Results of these analyses suggest that olanzapine , as therapeutically administered to patients with schizophrenia and related psychoses , does not contribute to QTc prolongation result ing in potentially fatal ventricular arrhythmias The symptom response and side-effects of olanzapine and risperidone were compared in patients with recent onset schizophrenia . Actively symptomatic patients ( n=44 ) r and omly received olanzapine 15 mg ( median dose ) or risperidone 4 mg ( median dose ) . Symptom response and side-effects were measured during a 6–10-week treatment study . No major differences were observed between the two treatment groups . Symptoms improved significantly on the Positive and Negative Syndrome Scale total score , positive subscale and general psychopathology subscale for both treatment groups . Using five symptom dimensions , both drugs were effective in treating positive symptoms and agitation/excitement symptoms , and neither olanzapine or risperidone influenced disorganization and depression symptoms . Results on the negative symptoms subscale and symptom dimension were inconclusive . No major differences were found in the frequency of the reported side-effects akathisia , parkinsonism and weight gain . These data indicate that the differences between olanzapine and risperidone in symptom response are small . In spite of the relatively low power of the study , we could exclude the presence of substantially different treatment effects between olanzapine and risperidone BACKGROUND While some cognitive accounts of disorganized speech , or thought disorder , in schizophrenia have emphasized failures in working memory/discourse planning or selective attention , we have suggested that thought disorder resides in the semantic system . In this study we assessed the effect of neuroleptic medication on thought disorder and semantic processing . METHODS Seventeen patients with schizophrenia were assessed while receiving neuroleptic medications and in crossover fashion , placebo . A number of measures were obtained : clinical ly rated thought disorder ( using the Thought , Language and Communication Scale ) ; working memory letter number span ) ; lexical integrity ( naming and receptive vocabulary ) ; and , semantic priming of intracategorical word pairs . RESULTS Semantic priming measures improved with neuroleptic medication , as did clinical ly rated thought disorder . No other measure changed significantly . Priming selectively covaried with changes in thought disorder . CONCLUSION Changes in spreading semantic activation , measured in a semantic priming paradigm and presumably brought about by neuroleptics ' influence on dopaminergic neuromodulatory systems , might reflect changes in the biases of pre-existing associative networks that favour or increase the accessibility of representations related by shared features . This study also has implication s for the architecture of normal language in that a dissociation between the lexical and semantic levels was observed , due to the selective compromise of tasks dem and ing semantic processing BACKGROUND This study compared the efficacy and safety of 4 therapeutically relevant strategies for switching clinical ly stable patients from a conventional antipsychotic drug or risperidone to olanzapine . METHOD Two hundred nine out patients with a DSM-IV diagnosis of schizophrenia or schizo-affective disorder who were clinical ly stable while being treated with a conventional antipsychotic drug or risperidone were openly r and omly assigned to either abrupt or gradual discontinuation of their prior antipsychotic drug . Patients were further r and omly assigned in a double-blind fashion to immediate olanzapine initiation ( olanzapine , 10 mg q.d . for 3 weeks ) or stepwise initiation ( a sequence of 1 week each on placebo ; olanzapine , 5 mg q.d . ; and olanzapine , 10 mg q.d . ) . The efficacy of these 4 switching paradigms was assessed using the Clinical Global Impressions (CGI)-Improvement scale , Patient 's Global Impressions (PGI)-Improvement scale , and Positive and Negative Syndrome Scale ( PANSS ) . Safety assessment s included ratings for extrapyramidal symptoms , cognitive impairment , adverse events , laboratory parameters , weight change , and vital signs . RESULTS The paradigm of gradual antipsychotic drug discontinuation combined with an initial full dose of olanzapine , 10 mg/day , had the most favorable efficacy and tolerability profile overall . By week 3 , the majority of completing patients on all 4 switching paradigms were either improved or clinical ly unchanged ( > 90 % ) . No clinical ly significant differences between switching paradigms were seen in laboratory values or vital signs . CONCLUSION In this study , switching clinical ly stable out patients with a diagnosis of schizophrenia or schizoaffective disorder to olanzapine was most successful when a full therapeutic dose of olanzapine was immediately initiated while gradually discontinuing prior conventional antipsychotic drug or risperidone treatment . Overall , switching was achieved without increased vulnerability to relapse or to occurrence of clinical ly burdensome antipsychotic drug withdrawal symptoms in the majority of patients Objective In patients with schizophrenia , risperidone and olanzapine are the two most commonly used atypical anti-psychotics . A recent meta- analysis based on r and omized trials suggests that , in the long term , olanzapine can have a lower frequency of treatment discontinuation ( or dropout ) in comparison with risperidone . To better test this hypothesis , our observational study was aim ed at assessing whether or not this advantage of olanzapine versus risperidone could be confirmed in a patient series examined in an observational setting . Methods Our study was based on a retrospective multi-centre observational design . We collected the following information from each patient : demographic characteristics ; current anti-psychotic treatment ( olanzapine or risperidone , under the condition of a stable therapy over months −1 to −4 ) ; cumulative dose of the drug ; previous anti-psychotic treatment ( during months −5 , −6 , −7 and /or , when available , also before month −7 ) ; daily dose and treatment duration . Our primary analysis traced back the patient ’s history from the date of enrollment retrospectively up to month −7 . The secondary analysis followed-up the patient ’s history prior to month −7 , thus extending this retrospective recording as long as possible ( depending on what information was actually available for individual patients ) . Results The patients were enrolled from 31 institutions . In our primary analysis ( months −1 to −7 ) , a total of 144 patients were included ; in this subgroup treated with olanzapine or risperidone as initial drug ( n=94 ) , we observed 4 of 54 switches from olanzapine to risperidone and 11 of 40 switches from risperidone to olanzapine ( P=0.01 ) . A total of 454 patients were enrolled in our secondary analysis ( from month −1 up to month −73 ) ; the same comparison showed 9 of 236 switches from olanzapine to risperidone and 17 of 150 switches from risperidone to olanzapine ( P=0.004 ) . Conclusion Our analysis confirms the results of a recent meta- analysis and shows that olanzapine might imply a lower risk of dropout than risperidone Atypical antipsychotics are commonly used in the management of schizophrenia in late life with evidence suggesting they induce lower rates of motor disturbance , but have similar efficacy to conventional antipsychotics . Trials in the elderly have been either retrospective , small , of short duration or of a single‐arm design OBJECTIVE To examine the effects of risperidone and olanzapine on cognitive functioning in elderly patients with schizophrenia or schizoaffective disorder . METHOD One hundred seventy-six elderly in patients and out patients with schizophrenia or schizoaffective disorder were enrolled in this multicenter , double-blind trial . After their antipsychotic medications were tapered for 1 week , patients were r and omly assigned to receive either risperidone 1 to 3 mg/day or olanzapine 5 to 20 mg/day for 8 weeks . Performance on the Continuous Performance Test ( CPT ) , Serial Verbal Learning Test ( SVLT ) , TMT ( Trail Making Test ) Parts A and B , Wisconsin Card Sorting Test ( WCST ) , and Verbal Fluency Examinations ( VFE ) was assessed at baseline and at end point . RESULTS Patients in the risperidone group had improved scores on at least one test of attention , memory , executive function , and verbal fluency , and those in the olanzapine group had improved scores on at least one test of attention and memory function . Scores on the TMT Part B , WCST total errors ( executive function domain ) , and the VFE improved significantly from baseline in the risperidone group but not in the olanzapine group . No significant differences in change scores between the two groups were found . Higher baseline scores on each test predicted more improvement at endpoint . CONCLUSIONS Low doses of risperidone and olanzapine improve cognitive function in elderly patients with schizophrenia or schizoaffective disorder . Consistent with research in younger population s , these improvements occur in aspects of cognitive functioning related to functional outcome OBJECTIVE Clinical factors predicting weight change in patients with schizophrenia and related disorders during acute treatment with the antipsychotic drugs olanzapine , risperidone , and haloperidol were sought through retrospective analyses . METHOD Six-week body-weight data from 2 trials , study 1 comparing olanzapine and haloperidol ( N = 1,369 ) and study 2 olanzapine and risperidone ( N = 268 ) , were analyzed . Effects of 8 clinical ly relevant covariates -- therapy , clinical outcome ( Brief Psychiatric Rating Scale ) , baseline body mass index ( B BMI ) , increased appetite , age , gender , race , and dose -- on weight were compared . RESULTS In study 1 , olanzapine ( vs. haloperidol ) therapy , better clinical outcome , lower B BMI , and nonwhite race significantly affected weight gain . Effects of increased appetite and male gender on weight gain were significant for olanzapine but not for haloperidol . In study 2 , better clinical outcome , lower B BMI , and younger age significantly affected weight gain . Increased appetite was more frequent during olanzapine treatment than during haloperidol , but not significantly different from risperidone . Significant differences in effect on weight change were found between olanzapine and haloperidol but not between olanzapine and risperidone . No evidence was found that lower antipsychotic drug doses were associated with lower weight gain . CONCLUSION This report identifies predictive factors of acute weight change in patients with schizophrenia . Similar factors across antipsychotic drugs in predicting greater weight gain included better clinical outcome , low B BMI , and nonwhite race . Factors differing between conventional ( haloperidol ) and atypical ( olanzapine ) agents included increased appetite and gender . Choice of atypical antipsychotic drug ( olanzapine vs. risperidone ) was of minor importance with regard to influence on acute weight gain BACKGROUND There has been considerable support for the observation that atypical antipsychotics have a broader range of therapeutic effects than traditional antipsychotics . We are exploring whether this exp and ed clinical efficacy can also be seen in patients with treatment-resistant schizophrenia . METHOD The subjects were 157 treatment-resistant in patients diagnosed with DSM-IV schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week double-blind trial and rated with a st and ard measure of clinical antipsychotic efficacy ( Positive and Negative Syndrome Scale [ PANSS ] ) . Factor analysis at baseline and endpoint together with changes in 5 PANSS-derived factors were examined . Data were gathered from June 1996 to December 1999 . RESULTS The underlying PANSS factor structure , as indicated by the factor loadings , was essentially identical at baseline and endpoint . At baseline , the excitement factor was followed by the positive , negative , cognitive , and depression/anxiety factors , explaining 49.4 % of the total variance . At endpoint , the positive factor was followed by the negative , excitement , cognitive , and depression/anxiety factors , explaining 55.5 % of the total variance . The endpoint data indicated statistically significant ( p < .05 ) improvements over time on the positive factor for all 3 atypicals , but not for haloperidol . The negative factor showed significant improvement for clozapine and olanzapine , with significant worsening for haloperidol . Clozapine , olanzapine , and risperidone were superior to haloperidol on the negative factor , while clozapine was also superior to risperidone . The cognitive factor showed significant improvement for all atypicals , as did the depression/anxiety factor . Only clozapine showed improvement on the excitement factor and was superior to both haloperidol and risperidone . CONCLUSIONS Treatment with atypical antipsychotics did not substantially change the underlying PANSS 5-factor structure . However , antipsychotic treatment with all 3 atypical medications was associated with significant improvements on 3 of 5 syndromal domains ( positive , cognitive , and depression/anxiety ) of schizophrenia . Clozapine and olanzapine also showed improvement on the negative factor . Only clozapine was associated with improvement on the excitement domain . This finding confirms that atypicals are associated with improvement of an exp and ed spectrum of symptoms in treatment-resistant patients BACKGROUND The relative effectiveness of second-generation ( atypical ) antipsychotic drugs as compared with that of older agents has been incompletely addressed , though newer agents are currently used far more commonly . We compared a first-generation antipsychotic , perphenazine , with several newer drugs in a double-blind study . METHODS A total of 1493 patients with schizophrenia were recruited at 57 U.S. sites and r and omly assigned to receive olanzapine ( 7.5 to 30 mg per day ) , perphenazine ( 8 to 32 mg per day ) , quetiapine ( 200 to 800 mg per day ) , or risperidone ( 1.5 to 6.0 mg per day ) for up to 18 months . Ziprasidone ( 40 to 160 mg per day ) was included after its approval by the Food and Drug Administration . The primary aim was to delineate differences in the overall effectiveness of these five treatments . RESULTS Overall , 74 percent of patients discontinued the study medication before 18 months ( 1061 of the 1432 patients who received at least one dose ) : 64 percent of those assigned to olanzapine , 75 percent of those assigned to perphenazine , 82 percent of those assigned to quetiapine , 74 percent of those assigned to risperidone , and 79 percent of those assigned to ziprasidone . The time to the discontinuation of treatment for any cause was significantly longer in the olanzapine group than in the quetiapine ( P<0.001 ) or risperidone ( P=0.002 ) group , but not in the perphenazine ( P=0.021 ) or ziprasidone ( P=0.028 ) group . The times to discontinuation because of intolerable side effects were similar among the groups , but the rates differed ( P=0.04 ) ; olanzapine was associated with more discontinuation for weight gain or metabolic effects , and perphenazine was associated with more discontinuation for extrapyramidal effects . CONCLUSIONS The majority of patients in each group discontinued their assigned treatment owing to inefficacy or intolerable side effects or for other reasons . Olanzapine was the most effective in terms of the rates of discontinuation , and the efficacy of the conventional antipsychotic agent perphenazine appeared similar to that of quetiapine , risperidone , and ziprasidone . Olanzapine was associated with greater weight gain and increases in measures of glucose and lipid metabolism OBJECTIVE To investigate the effects of the atypical antipsychotic drugs risperidone , olanzapine , quetiapine , and perospirone on the subjective quality of sleep in patients with schizophrenia . METHOD Subjects were 92 in patients ( mean age = 59.9 years ) who had been receiving treatment with conventional antipsychotic drugs and who met the DSM-IV criteria for schizophrenia . Subjects were r and omly assigned to receive 1 of 4 atypical antipsychotic drugs ( olanzapine , perospirone , quetiapine , and risperidone ) . Subjective sleep quality and psychopathology were assessed twice : at baseline and 8 weeks after switching . Data were collected from June 2001 to December 2001 . Subjective sleep quality was assessed by the Pittsburgh Sleep Quality Index ( PSQI ) , and psychopathology was measured by the Positive and Negative Syndrome Scale ( PANSS ) . RESULTS Subjective sleep quality as assessed by the PSQI was significantly improved with administration of olanzapine , risperidone , or quetiapine , but not with perospirone , in comparison with conventional antipsychotic drugs . Multiple regression analysis revealed that the improvement of sleep quality with administration of atypical antipsychotic drugs was predicted by poor sleep quality at baseline . In addition , improvement of sleep quality was significantly correlated with improvement of negative symptoms as assessed by the PANSS . CONCLUSION These results demonstrated that atypical antipsychotic drugs improved subjective quality of sleep in patients with schizophrenia compared with conventional antipsychotic drugs , suggesting that the marked potency of serotonin-2 receptor blockade in atypical antipsychotic drugs may be involved in the mechanism of this improvement . These improvements were correlated with improvement of negative symptoms This double-blind , r and omized , multicenter study investigated the use of divalproex with an antipsychotic agent in patients hospitalized for acute exacerbation of schizophrenia . Patients ( n=249 ) who met DSM-IV criteria for schizophrenia were r and omly assigned to receive olanzapine monotherapy , risperidone monotherapy , divalproex plus olanzapine , or divalproex plus risperidone for 28 days . Divalproex was initiated at 15 mg/kg/day and titrated over 12 days to a maximum dosage of 30 mg/kg/day . Olanzapine and risperidone , were , respectively , initiated at 5 and 2 mg/day and were titrated over the first 6 days to respective target fixed daily dosages of 15 and 6 mg/day . Improvements from baseline were observed at all evaluation points throughout the 28-day treatment period in the two combination therapy and the two antipsychotic monotherapy groups , with statistically significant treatment differences favoring combination therapy as soon as day 3 for Positive and Negative Syndrome Scale ( PANSS ) total score , derived Brief Psychiatric Rating Scale ( BPRSd ) total score , as well as PANSS and BPRSd subscales . These findings were confirmed in post hoc repeated- measures analyses of variance in which treatment differences favoring combination therapy were observed for PANSS total ( p=0.020 ) and PANSS positive scale scores ( p=0.002 ) . Both combination therapy and antipsychotic monotherapy were well tolerated . Treatment with divalproex in combination with an atypical antipsychotic agent result ed in earlier improvements in a range of psychotic symptoms among acutely hospitalized patients with schizophrenia . Further evaluation is warranted to confirm these findings OBJECTIVE This study compared the specific antihostility effects of atypical antipsychotic monotherapy ( olanzapine or risperidone ) with that of combination treatment with divalproex sodium among patients with schizophrenia experiencing an acute psychotic episode . METHODS A total of 249 in patients with schizophrenia were r and omly assigned to receive olanzapine plus placebo , olanzapine plus divalproex , risperidone plus placebo , or risperidone plus divalproex in a double-blind , 28-day multicenter trial . The target daily dose was 15 milligrams for olanzapine , 6 milligrams for risperidone , and up to 30 milligrams per kilogram ( minimum , 15 milligrams per kilogram ) for divalproex . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the PANSS items reflecting positive symptoms of schizophrenia ( delusions , suspiciousness/persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinatory behavior ) . RESULTS Combination treatment with risperidone or olanzapine plus divalproex was associated with different scores on the hostility item of the PANSS compared with antipsychotic monotherapy . Combination therapy had a significantly greater antihostility effect at days 3 and 7 than monotherapy . This result was not seen beyond the first week of treatment , but there was a trend toward a difference in effect for the entire treatment period . The effect on hostility appears to be statistically independent of antipsychotic effect on other PANSS items reflecting delusional thinking , a formal thought disorder , or hallucinations . CONCLUSIONS Divalproex sodium may be useful as an adjunctive agent in specifically reducing hostility in the first week of treatment with risperidone or olanzapine among patients with schizophrenia experiencing an acute psychotic episode Summary . Objectives : To evaluate and compare the drug response and side effects of adolescents with schizophrenia treated with olanzapine , risperidone , and haloperidol . Methods : Forty-three patients were treated with olanzapine ( n = 19 ) , risperidone ( n = 17 ) and haloperidol ( n = 7 ) for 8 weeks in an open clinical trial . Clinical improvement was evaluated with the Positive and Negative Syndrome Scale ( PANSS ) , and side effects with the Udvalg for Kliniske Undersogelser ( UKU ) Side Effect Rating Scale . Results : Significant clinical improvement was observed by week 4 for all medications . Olanzapine and haloperidol induced fatigability more frequently than risperidone . Haloperidol was associated with a higher frequency of depression and more severe extrapyramidal symptoms . Conclusions : To the best of our knowledge this is the first study in adolescents to compare the efficacy and side effects of three most commonly prescribed antipsychotic medications . Olanzapine , risperidone and haloperidol appear to be equally effective for the treatment of schizophrenia in adolescent in patients but have different side effect profiles OBJECTIVE To determine whether severity of obsessive-compulsive symptoms ( OCS ) differs during treatment with olanzapine or risperidone and to establish whether duration of antipsychotic treatment is related to severity of OCS . METHOD We conducted a prospect i ve study of consecutively hospitalized young patients ( mean age = 22.4 years ) with DSM-IV schizophrenia or related disorders ( N = 113 ) who were treated with olanzapine or risperidone . Olanzapine or risperidone was r and omly prescribed for patients who were drug-naive or were treated with typical antipsychotics before admission ( N = 36 ) . Patients who had started olanzapine ( N = 39 ) or risperidone treatment ( N = 23 ) prior to admission continued with that medication if they showed initial clinical response . Patients who prior to admission started olanzapine ( N = 6 ) or risperidone ( N = 9 ) but showed no response or suffered from adverse effects switched at admission to risperidone or olanzapine , respectively . Medical records , parents , and patients revealed information on duration of treatment and compliance with olanzapine or risperidone prior to admission . The Yale-Brown Obsessive Compulsive Scale ( YBOCS ) was administered at admission and 6 weeks thereafter . RESULTS At baseline and 6-week assessment s , OCS were found in about 30 % of 106 evaluable cases and 15 % met DSM-IV criteria for obsessive-compulsive disorder . No differences in OCS were found in the patients r and omly assigned to olanzapine or risperidone . The 35 subjects treated with olanzapine at both assessment s had significantly ( p = .01 ) more severe OCS at week 6 than the 20 subjects treated with risperidone at both assessment s. Duration of treatment with olanzapine was significantly ( p < .01 ) related to severity of OCS . CONCLUSION There are no differences in the short-term propensity of olanzapine or risperidone to induce or exacerbate OCS . However , severity of OCS was associated with duration of treatment with olanzapine Rationale First generation antipsychotics induce extrapyramidal motor symptoms ( EPS ) , presumably through dopamine D2 receptor blockade at the dorsal striatum . This may also produce impairment of cognitive processes , such as procedural learning , that are dependent on this region . Haloperidol and , to a lesser extent , risperidone , are active in the dorsal striatum and may induce EPS and impairment of procedural learning . In contrast , the prototypical second-generation antipsychotic , clozapine , is less active in the dorsal striatum and does not induce EPS or impair procedural learning . Olanzapine is pharmacologically similar to clozapine and has a low incidence of EPS induction . Objectives To assess the hypothesis that olanzapine would not have a deleterious effect on procedural learning . Methods Thirty-nine subjects with early phase schizophrenia were r and omly assigned to double blind treatment with haloperidol , risperidone , or olanzapine . They were administered the Tower of Toronto test at an unmedicated baseline and again following 6 weeks and 6 months of treatment . Results Procedural learning , defined as the improvement observed between two blocks of five trials of the Tower of Toronto , was preserved after 6 weeks of all three treatments but showed a substantial decline after 6 months of treatment with haloperidol or risperidone . Conclusions These data are consistent with the differential activity of the three medications in dorsal striatum structures and suggest that the advantages of olanzapine over haloperidol and risperidone in relation to extrapyramidal syndromes may also generalize to procedural learning . The results also suggest that the procedural learning disadvantages of haloperidol and risperidone accrue slowly but are apparent after 6 months of treatment This pilot study was undertaken to estimate the acute antipsychotic effect size and side effect propensity of risperidone and olanzapine in the pediatric population , in comparison to haloperidol , a conventional antipsychotic with established efficacy . Risperidone and olanzapine are widely used as first-line treatments to ameliorate psychotic symptoms in youth , but their abilities to specifically treat children and adolescents presenting due to psychotic symptoms have not been rigorously studied . Subjects , selected because of prominent positive psychotic symptoms , were r and omly assigned to double-blind , parallel treatment with risperidone , olanzapine , or haloperidol for 8 weeks . The primary outcome was reduction in the Brief Psychiatric Rating Scale for Children total score from baseline to termination . An exploratory , descriptive analysis was done to compare the three treatments . A total of 50 patients , 8–19 years , participated . All treatments reduced symptoms significantly with p-values ( corrected for multiple comparisons ) of 0.0018 for each of the atypical agents and 0.012 for haloperidol . In all , 88 % of subjects treated with olanzapine , 74 % treated with risperidone , and 53 % treated with haloperidol met response criteria . The primary side effects observed in all patients were mild to moderate sedation , extrapyramidal symptoms , and weight gain . Risperidone and olanzapine acutely reduced psychotic symptoms in this pediatric sample . Exploratory comparisons indicate the magnitude of the antipsychotic response with these atypical agents is comparable to that observed with haloperidol . However , youth treated with risperidone and olanzapine experienced weight gain and extrapyramidal effects that appear more prevalent and severe than reported in adults OBJECTIVE This study compared the specific antiaggressive effects of clozapine with those of olanzapine , risperidone , and haloperidol . METHODS A total of 157 in patients with schizophrenia or schizoaffective disorder and a history of suboptimal treatment response were r and omly assigned to receive clozapine , olanzapine , risperidone , or haloperidol in a double-blind 14-week trial . The trial was divided into two periods : eight weeks during which the dosage was escalated and then fixed , and six weeks during which variable dosages were used . The hostility item of the Positive and Negative Syndrome Scale ( PANSS ) was the principal outcome measure . Covariates included the items that reflect positive symptoms of schizophrenia ( delusions , suspiciousness or feelings of persecution , gr and iosity , unusual thought content , conceptual disorganization , and hallucinations ) and the sedation item of the Nurses Observation Scale for Inpatient Evaluation ( NOSIE ) . RESULTS Patients differed in their treatment response as measured by the hostility item of the PANSS . The scores of patients taking clozapine indicated significantly greater improvement than those of patients taking haloperidol or risperidone . The effect on hostility appeared to be independent of the antipsychotic effect of clozapine on other PANSS items that reflect delusional thinking , a formal thought disorder , or hallucinations and independent of sedation as measured by the NOSIE . Neither risperidone nor olanzapine showed superiority to haloperidol . CONCLUSION Clozapine has a relative advantage over other antipsychotics as a specific antihostility agent OBJECTIVE This international , multicenter double-blind trial was design ed to compare the therapeutic profile of an atypical antipsychotic , olanzapine , with that of a conventional dopamine D2 antagonist , haloperidol . METHOD A total of 1,996 patients at 174 sites in Europe and North America were r and omly assigned to treatment with olanzapine ( N = 1,336 ) or haloperidol ( N = 660 ) over 6 weeks . The primary efficacy analysis involved the mean change from baseline to endpoint in total scores on the Brief Psychiatric Rating Scale ( BPRS ) . Secondary analyses included comparisons of the mean change in positive and negative symptoms , comorbid depression , extrapyramidal symptoms , and overall drug safety . RESULTS Olanzapine demonstrated clinical results superior to those of haloperidol on overall improvement according to the BPRS and on every secondary measure , including depression . Olanzapine was also associated with significantly fewer discontinuations of treatment due to lack of drug efficacy or adverse events . Substantially more olanzapine-treated patients ( 66.5 % ) than haloperidol-treated patients ( 46.8 % ) completed 6 weeks of therapy . Statistically significant advantages of olanzapine treatment were related to 1 ) change in negative symptoms , 2 ) extrapyramidal symptom profile , 3 ) effect on prolactin levels , and 4 ) response rate . CONCLUSIONS Olanzapine shows a superior and broader spectrum of efficacy in the treatment of schizophrenic psychopathology , with a substantially more favorable safety profile , than haloperidol . It meets several of the criteria for a novel atypical antipsychotic agent BACKGROUND Clinical trials indicate that glycine site agonists of the N-methyl-D-aspartate ( NMDA ) receptors may reduce negative and cognitive symptoms in treatment-resistant schizophrenia when used as adjuvants to conventional antipsychotics but possibly not to clozapine . In this study , we assessed whether high-dose glycine may also be therapeutically beneficial when added to olanzapine and risperidone treatment . METHODS Seventeen olanzapine- or risperidone-treated schizophrenia patients participated in a double-blind , placebo-controlled , 6-week crossover treatment trial with.8 g/kg/day glycine added to their ongoing antipsychotic medication . Clinical assessment s were performed biweekly throughout the study . Clinical laboratory parameters and amino acid serum levels were monitored . RESULTS Glycine treatment was well tolerated and result ed in a significant ( p < .0001 ) 23 % + /- 8 % reduction in negative symptoms . Significant improvements were also registered in cognitive and positive symptoms . The negative symptoms improvement remained significant even following covariation for changes in other symptom clusters and extrapyramidal side effects . High posttreatment glycine serum levels significantly predicted ( r = .60 ) clinical response . CONCLUSIONS These findings indicate that the efficacy of olanzapine and risperidone may be augmented using high-dose adjuvant glycine treatment and suggest that these atypical antipsychotics may affect NMDA receptor-mediated neurotransmission differently than clozapine Rationale The absence of a relationship between cognitive deficit treatment response and positive symptom treatment response is often assumed , and few data have shed light on this issue . Most of these data have been collected using st and ard neuropsychological measures , which are ill- design ed to assess the types of neurocognitive disturbances associated with psychotic symptoms . This study investigates the effect of treatment on source monitoring performance and its relation to the reduction of certain psychotic symptoms associated with the inability to identify self-generated mental events , known as " autonoetic agnosia " . Objectives To determine whether risperidone , olanzapine , and haloperidol were differentially effective in reducing autonoetic agnosia and whether changes in this aspect of cognition were related to reduction of specific symptoms of psychosis . Methods From a cohort of 49 patients diagnosed with schizophrenia by DSM-IV criteria and r and omly assigned to double-blind treatment with risperidone , olanzapine , or haloperidol , 16 patients were identified with symptoms believed to reflect autonoetic agnosia ( " target symptoms " ) as assessed with the Schneiderian Symptom Rating Scale , and then evaluated during a baseline period , and then at 1 , 2 , and 3 weeks . Autonoetic agnosia was assessed as the ability of a patient to distinguish self-generated words from both experimenter-generated words and pictorially presented words . Results Analysis of patients from all treatment groups found a significant reduction in the number of " target " Schneiderian symptoms . Discrimination for items from the self-generated and heard sources significantly improved with treatment , as did the number of self-generated items that patients remembered as coming from the heard source ( " self-hear errors " ) . The correlation between improvement in recognition of self-generated items and reduction in target Schneiderian symptoms after 2 weeks of treatment suggested a modest relationship between symptom improvement and changes in autonoetic agnosia . Conclusions While the differences between medications were not statistically significant , antipsychotic medication in general was associated with improvements in symptoms and cognitive deficits that may underlie autonoetic agnosia . Improvement of autonoetic agnosia was a weak predictor of positive symptom improvement in a limited sample BACKGROUND Depressive symptoms are common during the course of schizophrenia and may carry prognostic relevance . METHODS From a 28-week prospect i ve , double-blind , r and omized study of olanzapine and risperidone , a post hoc evaluation of changes on the Positive and Negative Syndrome Scale ( PANSS ) depression cluster ( PDC ) and the subsequent risk of relapse were analyzed by logistic regression . RESULTS Olanzapine was associated with a significantly higher categorical rate of improvement on the PANSS depression cluster ( > or = 7 points ) ( p < .05 ) . Although the baseline severity of depressive symptoms was not a significant predictor of relapse , the degree of acute ( 8-week ) mood improvement on the PANSS depression cluster ( but neither negative or positive symptom changes ) was related to the probability of a subsequent psychotic relapse . Acute mood improvement with olanzapine was inversely related to a nonsignificantly lower risk of relapse . However , an opposite and significant relationship was observed among risperidone-treated subjects . Risperidone-treated subjects with a greater degree of acute mood change were both 3.58 times more likely to relapse than their risperidone counterparts who had experienced less mood improvement ( p = .008 ) and 8.55 times more likely than olanzapine-treated subjects who had had similar mood improvements ( p = .001 ) . CONCLUSIONS These data suggest the underlying pharmacologic differences between the two drugs may bestow different rates of longer-term mood stabilization and relapse prevention . In a second series of analyses , worsening on the PANSS depression cluster in the 4 weeks or less preceding a clinical relapse was a significant prodromal predictor of relapse among all subjects . As a whole , subjects with a worsening on the PDC demonstrated a 1.77 times higher risk of a relapse during the subsequent 4 weeks ( p = .001 ) . Among this mood-worsening stratum , risperidone-treated patients were 3.51 times more likely to relapse in those next 4 weeks ( p = .005 ) than their olanzapine counterparts . Future comparative drug studies in this area will further contribute to our underst and ing of the pathophysiology of mood change and its relationship to psychosis , including clinical relapse and how newer agents may differ in their respective delivery of long-term treatment outcomes OBJECTIVE To evaluate the safety and tolerability of long-term treatment with olanzapine versus risperidone in schizophrenic out patients with prominent negative symptoms . METHODS This was a multi-center , r and omised , open-label , parallel , dose-flexible , 1 year study of out patients with schizophrenia ( DSM-IV criteria ) with prominent negative symptoms ( SANS Global score > or = 10 ) . Safety was evaluated by recording treatment-emergent adverse events , vital signs , body weight and , when available , laboratory parameters . Extrapyramidal symptoms ( EPS ) were evaluated by a question naire based on the UKU scale , and sexual dysfunction by the Psychotropic-Related Sexual Dysfunction Question naire ( PRSexDQ ) . RESULTS The mean ( + /- SD ) modal dose throughout the study was 12.3 ( + /- 6.3 ) mg/day for olanzapine and 5.2 ( + /- 2.5 ) mg/day for risperidone . EPS were significantly more frequent in the risperidone-treated patients 50.4 % versus 28.9 % for olanzapine ( p = 0.0006 ) . Olanzapine patients showed significantly greater reductions ( improvement ) from baseline in the PRSexDQ score ( p=0.0292 ) and risperidone patients reported significantly more sexual adverse events ( 21.1 % versus 7.3 % for olanzapine ; p=0.0018 ) . Mean body weight gain was not significantly different at endpoint ( 3.5 kg gained with olanzapine versus 1.9 kg gained with risperidone ; p=0.3522 ) , but the proportion of patients showing a body weight increase > or = 7 % was higher among the olanzapine-treated patients ( 37.8 % versus 16.8 % ; p=0.0012 ) . CONCLUSIONS Significantly less treatment-emergent extrapyramidal and sexual adverse events were observed in patients treated with olanzapine compared to those treated with risperidone . Mean body weight increases with both drugs were not significantly different after one year . Olanzapine patients presented a significantly higher incidence of clinical ly important body weight increase when compared with patients treated with risperidone OBJECTIVE The association of hyperglycemia and hypercholesterolemia with use of atypical antipsychotics has been documented in case reports and uncontrolled studies . The authors ' goal was to assess the effects of clozapine , olanzapine , risperidone , and haloperidol on glucose and cholesterol levels in hospitalized patients with schizophrenia or schizoaffective disorder during a r and omized double-blind 14-week trial . METHOD One hundred fifty-seven patients with schizophrenia or schizoaffective disorder who were in patients at four hospitals were originally included in the study . The 14-week trial consisted of an 8-week fixed-dose period and a 6-week variable-dose period . Planned assessment s included fasting glucose and cholesterol , which were collected at baseline and at the end of the 8-week period and the following 6-week period . RESULTS One hundred eight of the 157 patients provided blood sample s at baseline and at least at one point after r and om assignment to clozapine , olanzapine , risperidone , or haloperidol during the treatment trial . Seven of these patients had diabetes ; their glucose levels were > 125 mg/dl at baseline . Data from 101 patients were used for statistical analyses . During the initial 8-week period there was an overall significant increase in mean glucose levels . There were significant increases in glucose levels at the end of the 8-week fixed-dose period for patients given clozapine ( N=27 ) and those given haloperidol ( N=25 ) . The olanzapine group showed a significant increase of glucose levels at the end of the 6-week variable-dose period ( N=22 ) . Fourteen of the 101 patients developed abnormal glucose levels ( > 125 mg/dl ) during the trial ( six with clozapine , four with olanzapine , three with risperidone , and one with haloperidol ) . Cholesterol levels were increased at the end of the 8-week fixed-dose period for the patients given clozapine ( N=27 ) and those given olanzapine ( N=26 ) ; cholesterol levels were also increased at the end of the 6-week variable-dose period for patients given olanzapine ( N=22 ) . CONCLUSIONS In this prospect i ve r and omized trial , clozapine , olanzapine , and haloperidol were associated with an increase of plasma glucose level , and clozapine and olanzapine were associated with an increase in cholesterol levels . The mean changes in glucose and cholesterol levels remained within clinical ly normal ranges , but approximately 14 % of the patients developed abnormally high glucose levels during the course of their participation in the study Minimum doses of haloperidol might show similar efficacy and side-effects compared to atypical antipsychotics . The objectives of this study were to compare the efficacy of minimum doses of haloperidol with st and ard doses of risperidone and olanzapine on a 6-month open trial in first psychotic episode patients and to examine the effect of compliance on their outcome . Forty-two patients were recruited and started on flexible doses of these drugs . Olanzapine was given with no cost to the patients . Efficacy and side-effects were monitored every 3 months using st and ardized assessment s. Thirty patients completed the study . All treatment groups showed improvement in positive , negative and depressive symptoms . There were no differences in side-effects among them . The haloperidol group required higher doses of anticholinergics . The rate of treatment discontinuation was higher in the risperidone group due to the direct cost . Minimum doses of haloperidol might prove to be a good choice of treatment for patients with a first episode of psychosis BACKGROUND Prolactin levels are elevated to varying degrees by antipsychotics . Prolactin elevations may result in sexual and other adverse effects , and they may be related to antipsychotic effects . We used the data collected in a trial of antipsychotics to study the differential effect of these drugs on prolactin level , to explore the relation between clinical effects and prolactin level , and to determine the relationship between plasma levels of antipsychotics and prolactin level . METHOD Treatment-resistant patients ( 133 men , 24 women ) diagnosed with DSM-IV schizophrenia or schizoaffective disorder participated in a double-blind , r and omized , 14-week trial comparing clozapine ( N = 40 ) , olanzapine ( N = 39 ) , risperidone ( N = 41 ) , and haloperidol ( N = 37 ) . Plasma levels of prolactin and antipsychotics were determined at baseline and at weeks 5 , 8 , 10 , 12 , and 14 during the trial . Clinical effects were measured with the Positive and Negative Syndrome Scale and the Extrapyramidal Symptom Rating Scale . Statistical analyses were limited to the 75 men for whom repeated prolactin levels were available . Data were gathered from June 1996 to December 1999 . RESULTS Risperidone caused significant elevation of prolactin levels ( p < .05 ) that appeared to be dose-dependent . Clozapine and olanzapine were associated with decreases of prolactin , whereas haloperidol led to a minor , nonsignificant increase . Plasma olanzapine and prolactin levels were correlated . Prolactin levels were not related to clinical improvement or extrapyramidal side effects . CONCLUSION Antipsychotics show major differences in their effects on prolactin , and risperidone has clearly the most robust effect BACKGROUND This analysis compares the efficacy of risperidone and olanzapine in controlling negative and positive symptoms of chronic psychosis in older patients . METHOD Post hoc assessment s were made in a subset of risperidone-treated ( N = 19 ) and olanzapine-treated ( N = 20 ) older patients ( aged 50 to 65 years ) from a large international , multicenter , parallel , double-blind , 28-week study of patients aged 18 to 65 years ( N = 339 ) r and omly assigned to receive risperidone ( 4 - 12 mg/day ) or olanzapine ( 10 - 20 mg/day ) . Assessment s were made using repeated- measures analysis . RESULTS At both 8 weeks and 28 weeks , the magnitude of changes in Positive and Negative Syndrome Scale ( PANSS ) positive symptom subscale scores did not differ between treatment groups ( 8 weeks : risperidone , -6.5 ; olanzapine , -6.8 , p = .866 ; 28 weeks : risperidone , -6.5 ; olanzapine , -7.0 ; p = .804 ) . However , by the 8-week timepoint , olanzapine had reduced PANSS negative subscale scores significantly more than risperidone ( -8.8 vs. -4.9 , p = .032 ) . By the 28-week endpoint , olanzapine had continued to maintain significantly greater reduction in baseline-to-endpoint PANSS negative scores ( -8.1 vs. -3.5 , p = .032 ) and led to significantly greater reduction in scores on the Scale for the Assessment of Negative Symptoms ( SANS ) dimensions of affective flattening ( -5.2 vs. -0.6 , p = .033 ) and alogia ( -3.8 vs. -0.3 , p = .007 ) . Patients in the olanzapine treatment group also demonstrated numerically greater reduction of both SANS summary ( -3.7 vs. -1.0 , p = .078 ) and SANS composite scores ( -14.1 vs. -4.1 , p = .075 ) . CONCLUSION These data demonstrate that , in older patients with schizophrenia and related psychotic disorders , risperidone and olanzapine have approximately equal efficacy in controlling positive symptoms . However , olanzapine appears to be more efficacious in maintaining control over negative symptoms BACKGROUND This prospect i ve study measured adherence to conventional and atypical antipsychotics after hospital discharge in patients with a diagnosis of schizophrenia and schizoaffective disorder . We examined the interaction of several predictors such as gender , severity of illness , attitudes toward medications , side effects , and dose frequency . METHOD The sample consisted of consecutive r and omized and nonr and omized patients who were discharged from an inpatient unit with a DSM-IV diagnosis of schizophrenia or schizoaffective disorder between December 1995 and July 1999 . All patients were taking oral antipsychotics and consented to the use of an electronic adherence monitor at discharge . Medications were prescribed by usual care providers , and medication adherence was followed weekly for 3 months . The outcome measure was the medication adherence rate registered in the electronic monitors . RESULTS We found no significant difference in adherence between the combined groups of atypical and conventional antipsychotics . Individual medication analysis found better medication adherence with olanzapine in comparison with risperidone and conventional antipsychotics , but the difference disappeared in the final model controlling for dose frequency . Dose frequency , gender , and akathisia predicted adherence . CONCLUSIONS Olanzapine initially appeared to be associated with an adherence advantage over risperidone and conventional antipsychotics , but the apparent advantage may have been due to a usual care dose frequency practice that associated olanzapine more often with once-daily dosing . This study suggests that dose frequency is an important predictor of medication adherence . An important caveat is that these results apply only to short-term adherence OBJECTIVE The safety and efficacy of risperidone and olanzapine were compared in a double-blind trial that used doses widely accepted in clinical practice . METHOD Subjects ( N=377 ) who met DSM-IV criteria for schizophrenia or schizoaffective disorder were r and omly assigned to receive 2 - 6 mg/day of risperidone ( mean modal dose=4.8 mg/day ) or 5 - 20 mg/day of olanzapine ( mean modal dose=12.4 mg/day ) for 8 weeks . RESULTS The two study groups were similar at baseline except that the olanzapine group was slightly younger than the risperidone group . Seventy-five percent of the participants completed the trial , with no between-treatment differences in the proportion of dropouts . Similar proportions of the risperidone and olanzapine groups reported extrapyramidal symptoms ( 24 % and 20 % , respectively ) . Severity of extrapyramidal symptoms was low in both groups , with no between-group differences . Total Positive and Negative Syndrome Scale scores and scores on the five Positive and Negative Syndrome Scale factors were improved in both groups at week 8 ( subjects who completed the study ) and endpoint ( all subjects , including dropouts ) . There were overall between-treatment differences in efficacy . Comparison of individual factors found no significant differences at endpoint ; at week 8 , however , improvements on Positive and Negative Syndrome Scale factors for positive symptoms and anxiety/depression were greater with risperidone than olanzapine . An increase in body weight of > or = 7 % was seen in 27 % of olanzapine participants and 12 % of risperidone participants . CONCLUSIONS Both treatments were well tolerated and efficacious . The frequency and severity of extrapyramidal symptoms were similar in the two treatment groups . Greater reductions in severity of positive and affective symptoms were seen with risperidone than with olanzapine treatment among study completers . There was no measure on which olanzapine was superior . Greater weight gain was associated with olanzapine than with risperidone treatment Our objective was to compare lipid profiles of schizophrenic patients treated with conventional antipsychotics or risperidone to those of patients switched to olanzapine . Our results indicate that in patients switched to olanzapine , fasting serum lipids initially increased then returned to pretreatment levels , and endpoint lipid levels were not significantly different from those in patients remaining on conventional antipsychotics or risperidone Objective The effects of risperidone and olanzapine on cognitive functioning in patients with schizophrenia were compared in a r and omized , double-blind trial . Method Three hundred and seventy-seven patients were r and omly assigned to receive 2–6 mg/day of risperidone or 5–20 mg/day of olanzapine for 8 weeks . Cognitive function was assessed with a focused cognitive assessment battery ; in addition , extrapyramidal symptoms were assessed using the extrapyramidal symptom rating scale ( ESRS ) , and the positive and negative syndrome scale ( PANSS ) was rated for all patients . Results Treatment with these two atypical antipsychotic medications was associated with improved performance on the Wisconsin card sorting test , the trail-making test , the California verbal learning test , the continuous performance test , and some aspects of verbal fluency and spatial working memory . No differences in the effects of the drugs on any of the cognitive tests were noted . Correcting for the effects of anticholinergic treatment did not alter the magnitude of cognitive effects . Conclusions Atypical antipsychotic treatment is associated with wide-ranging benefits on cognitive functioning . Previous reports of greater benefits of olanzapine over risperidone in a small- sample pilot study were not substantiated . These results are not due in general to changes in clinical symptoms or movement disorders , suggesting a direct effect of atypical antipsychotic medications on cognitive deficits in schizophrenia A modification of an earlier rating scale for extrapyramidal system disturbance is described , and evidence for the validity and reliability of the scale is presented . The usefulness of the scale in studies of neuroleptic drugs is discussed . By its application it is possible to quantify extrapyramidal side effects and to separate them into four principal factors Abstract : The subjects were 157 treatment-resistant in patients diagnosed with chronic schizophrenia or schizoaffective disorder . They were r and omly assigned to treatment with clozapine , olanzapine , risperidone , or haloperidol in a 14-week , double-blind trial . Incidents of overt aggression were recorded and their severity was scored . The Positive and Negative Syndrome Scale was administered . Atypical antipsychotics showed an overall superiority over haloperidol , particularly after the first 24 days of the study when the dose escalation of clozapine was completed . Once an adequate therapeutic dose of clozapine was reached , it was superior to haloperidol in reducing the number and severity of aggressive incidents . Patients exhibiting persistent aggressive behavior showed less improvement of psychotic symptoms than the other patients . There was an interaction between aggressiveness , medication type , and antipsychotic response : risperidone and olanzapine showed better antipsychotic efficacy in patients exhibiting less aggressive behavior ; the opposite was true for clozapine . Clozapine appears to have superior antiaggresive effects in treatment-resistant patients ; this superiority develops after the patient has been exposed to an adequate dose regimen BACKGROUND A recent review suggested an association between using unpublished scales in clinical trials and finding significant results . AIMS To determine whether such an association existed in schizophrenia trials . METHOD Three hundred trials were r and omly selected from the Cochrane Schizophrenia Group 's Register . All comparisons between treatment groups and control groups using rating scales were identified . The publication status of each scale was determined and cl aims of a significant treatment effect were recorded . RESULTS Trials were more likely to report that a treatment was superior to control when an unpublished scale was used to make the comparison ( relative risk 1.37 ( 95 % CI 1.12 - 1.68 ) ) . This effect increased when a ' gold-st and ard ' definition of treatment superiority was applied ( RR 1.94 ( 95 % CI 1.35 - 2.79 ) ) . In non-pharmacological trials , one-third of ' gold-st and ard ' cl aims of treatment superiority would not have been made if published scales had been used . CONCLUSIONS Unpublished scales are a source of bias in schizophrenia trials The National Institute of Mental Health initiated the Clinical Antipsychotic Trials of Intervention Effectiveness ( CATIE ) program to evaluate the effectiveness of antipsychotic drugs in typical setting s and population s so that the study results will be maximally useful in routine clinical situations . The CATIE schizophrenia trial blends features of efficacy studies and large , simple trials to create a pragmatic trial that will provide extensive information about antipsychotic drug effectiveness over at least 18 months . The protocol allows for subjects who receive a study drug that is not effective to receive subsequent treatments within the context of the study . Medication dosages are adjusted within a defined range according to clinical judgment . The primary outcome is all-cause treatment discontinuation because it represents an important clinical endpoint that reflects both clinician and patient judgments about efficacy and tolerability . Secondary outcomes include symptoms , side effects , neurocognitive functioning , and cost-effectiveness . Approximately 50 clinical sites across the United States are seeking to enroll a total of 1,500 persons with schizophrenia . Phase 1 is a double-blinded r and omized clinical trial comparing treatment with the second generation antipsychotics olanzapine , quetiapine , risperidone , and ziprasidone to perphenazine , a midpotency first generation antipsychotic . If the initially assigned medication is not effective , subjects may choose one of the following phase 2 trials : ( 1 ) r and omization to open-label clozapine or a double-blinded second generation drug that was available but not assigned in phase 1 ; or ( 2 ) double-blinded r and omization to ziprasidone or another second generation drug that was available but not assigned in phase 1 . If the phase 2 study drug is discontinued , subjects may enter phase 3 , in which clinicians help subjects select an open-label treatment based on individuals ' experiences in phases 1 and 2 To more clearly clarify the efficacy of the atypical antipsychotics compared to conventional antipsychotics , we add data on the outcome of patients diagnosed with schizophrenia from two large , international clinical trials comparing olanzapine with haloperidol ( n = 1996 ) and olanzapine with risperidone ( n = 339 ) . Both studies comprised double-blinded , placebo controlled , r and om assignment trials . Health outcomes reported include : ( i ) time to discontinuation in the trial ; ( ii ) clinical relapse ; and ( iii ) time to drug non-compliance . When outcome was measured as time to discontinuation due to adverse events or lack of efficacy , olanzapine showed superiority over haloperidol and no difference compared to risperidone . Of those patients who had an initial response , there was no significant difference between olanzapine and haloperidol when outcome was measured using either : ( i ) 52-week relapse rates or ( ii ) time to first non-compliance . Using the measures of study discontinuation , relapse and non-compliance , in one trial the atypical antipsychotic olanzapine was superior to haloperidol , while in a second trial there were no differences between olanzapine and risperidone |
12,813 | 28,143,389 | ConclusionS BT may be not superior to NSBT on airway management training | Background Simulation-based training ( SBT ) has become a st and ard for medical education .
However , the efficacy of simulation based training in airway management education remains unclear .
Methods The aim of this study was to evaluate all published evidence comparing the effectiveness of SBT for airway management versus non-simulation based training ( NSBT ) on learner and patient outcomes . | BACKGROUND / PURPOSE Conventional training in bronchoscopy may increase patient 's discomfort and procedure-related morbidity . Computer-based bronchoscopy simulator ( CBBS ) permits the acquisition and evaluation of the necessary skills through a realistic bronchoscopic experience . This study was conducted to vali date the use of a CBBS system developed in Taiwan as a learning and assessment tool . METHODS Twenty novice bronchoscopists and 10 expert bronchoscopists were enrolled as subjects in this prospect i ve study . The 20 novice bronchoscopists were r and omized into two groups , which received conventional bronchoscopic training or CBBS training and then completed a satisfaction survey . Subsequently , the novices who received CBBS training underwent an observational performance trial and the results were compared with those of expert bronchoscopists . All 10 expert bronchoscopists completed a realism survey and observational trial after CBBS performance . RESULTS The satisfaction survey showed that the CBBS training program significantly increased participants ' satisfaction ( p = 0.002 ) and interest in learning ( p < 0.001 ) . The realism survey by the 10 expert bronchoscopists indicated that CBBS provides a favorable degree of realism with regard to the mechanical and visual parameters examined . Analysis of the performance results showed that the following parameters were capable of differentiating the participants by level of expertise : total procedure time ( p = 0.002 ) , percentage of bronchial segments entered ( p = 0.012 ) , percentage of bronchial segments identified ( p < 0.001 ) , percentage of repeated bronchial segments entered ( p = 0.004 ) , percentage of pathologies identified ( p < 0.001 ) , number of times that the bronchoscope tip collided with airway walls ( p = 0.013 ) , and number of times oral instruction was needed ( p = 0.01 ) . CONCLUSION CBBS is a valid training method that increases interest in learning and provides a favorable degree of virtual realism . It can also distinguish various levels of competence at actual bronchoscopy and may have a useful role in the bronchoscopic training curriculum INTRODUCTION The human patient simulator has proved to be an effective educational device for teaching physicians and paramedical personnel . METHODOLOGY To determine whether veterinary medicine students would benefit from similar educational sessions , 90 students each took a turn being the patient 's clinician as real-life scenarios were played out on the simulator . The students induced and maintained anesthesia on their patient and monitored vital signs . Several critical events were presented for the students to diagnose and treat as they occurred . All students su bmi tted a written evaluation of the course upon completion . The last 40 students were r and omly divided into two groups of 20 students each . The students in Group I experienced the simulator before their clerkship examination , and those in Group II took the examination before their simulator experience . RESULTS The students rapidly gained confidence in treating their simulated patient . This carried over to the clinical setting , where they appeared to be more confident when anesthetizing live patients . The simulator experience brought together much of the previous didactic material that they had been exposed to so they could appreciate its clinical relevance . The overwhelming response to the simulator experience was positive . The students in Group I had a significantly higher score on the clerkship examination dealing with concepts review ed by simulation than those in Group II , who engaged in self- study instead of the simulation exercise ( p < 0.001 ) . CONCLUSION We conclude that the human patient simulator was a valuable learning tool for students of veterinary medicine . It was exciting for the students to work with , made them deal with " real-life " scenarios , permitted them to learn without subjecting live patients to complications , enabled them to retrace their steps when their therapy did not correct the simulated patient 's problems , and facilitated correlation of their basic science knowledge with clinical data , thus accelerating their ability to h and le complex clinical problems in healthy and diseased patients Background With increasing pressure to use operating room time efficiently , opportunities for residents to learn fiberoptic orotracheal intubation in the operating room have declined . The purpose of this study was to determine whether fiberoptic orotracheal intubation skills learned outside the operating room on a simple model could be transferred into the clinical setting . Methods First-year anesthesiology residents and first- and second-year internal medicine residents were recruited . Subjects were r and omized to a didactic-teaching-only group ( n = 12 ) or a model-training group ( n = 12 ) . The didactic-teaching group received a detailed lecture from an expert bronchoscopist . The model-training group was guided , by experts , through tasks performed on a simple model design ed to refine fiberoptic manipulation skills . After the training session , subjects performed a fiberoptic orotracheal intubation on healthy , consenting , anesthetized , paralyzed female patients undergoing elective surgery with predicted “ easy ” laryngoscopic intubations . Two blinded anesthesiologists evaluated each subject . Results After the training session , the model group significantly outperformed the didactic group in the operating room when evaluated with a global rating scale ( P < 0.01 ) and checklist ( P < 0.05 ) . Model-trained subjects completed the fiberoptic orotracheal intubation significantly faster than didactic-trained subjects ( P < 0.01 ) . Model-trained subjects were also more successful at achieving tracheal intubation than the didactic group ( P < 0.005 ) . Conclusion Fiberoptic orotracheal intubation skills training on a simple model is more effective than conventional didactic instruction for transfer to the clinical setting . Incorporating an extraoperative model into the training of fiberoptic orotracheal intubation may greatly reduce the time and pressures that accompany teaching this skill in the operating room Abstract Simulation-based teaching ( SBT ) is increasingly used in medical education . As an alternative to other teaching methods there is a lack of evidence concerning its efficacy . The aim of this study was to evaluate the potency of SBT in anesthesia in comparison to problem-based discussion ( PBD ) with students in a r and omized controlled setting . Thirty-three fourth-year medical students attending a curricular anesthesiology course were r and omly allocated to either a session of SBT or a session of PBD on an emergency induction method . Ten days later all students underwent examination in a simulator . The performance of each student was evaluated by weighted tasks , established according to a modified Delphi process . Confidence and a multiple-choice question naire were additionally performed pre- and post-intervention . A total of 32 students completed the study . Participants in the SBT group presented with significantly higher self- assessment scores after the intervention than students in the PBD group . However , students in the SBT group achieved only slightly and statistically insignificantly higher scores in the theoretical and simulator examination ( p > 0.05 ) with only a moderate effect size of d = 0.52 . The current study demonstrates that both PBD and SBT lead to comparable short-term outcomes in theoretical knowledge and clinical skills . However , undesirably , SBT students overrated their anticipated clinical abilities and knowledge improvement OBJECTIVES The primary purpose of this study was to determine whether the endotracheal intubation ( ETI ) success rate is different among paramedic students trained on a human patient simulator versus on human subjects in the operating room ( OR ) . METHODS Paramedic students ( n = 36 ) with no prior ETI training received identical didactic and mannequin teaching . After r and omization , students were trained for ten hours on a patient simulator ( SIM ) or with 15 intubations on human subjects in the OR . All students then underwent a formalized test of 15 intubations in the OR . The primary outcome was the rate of successful intubation . Secondary outcomes were the success rate at first attempt and the complication rate . The study was powered to detect a 10 % difference for the overall success rate ( alpha = 0.05 , beta = 0.20 ) . RESULTS The overall intubation success rate was 87.8 % in the SIM group and 84.8 % in the OR group ( difference of 3.0 % [ 95 % confidence interval { CI } = -4.2 % to 10.1 % ; p = 0.42 ] ) . The success rate on the first attempt was 84.4 % in the SIM group and 80.0 % in the OR group ( difference of 4.4 % [ 95 % CI = -3.4 % to 12.3 % ; p = 0.27 ] ) . The complication rate was 6.3 % in the SIM group and 4.4 % in the OR group ( difference of 1.9 % [ 95 % CI = -2.9 % to 6.6 % ; p = 0.44 ] ) . CONCLUSIONS When tested in the OR , paramedic students who were trained in ETI on a simulator are as effective as students who trained on human subjects . The results support using simulators to teach ETI Background and objective The aim of the study was to compare the effectiveness of teaching of general anaesthesia induction to medical students using either full-scale simulation or traditional supervised teaching with patients in the operating theatre . Methods Forty-six fourth year students attending their course in anaesthesiology were enrolled . The students were r and omly assigned to two groups . The simulation group received training in the simulator . The traditional training group was supervised by a senior consultant anaesthetist . After the training sessions all students were tested in the simulator setting . The test was assessed using a 40-item evaluation list . Results Thirty-three per cent of students in the traditional group and 87 % of the students in the simulation group passed the test . Statistically significant differences were : request of glycopyrrolate ( P < 0.001 ) , SpO2 monitoring ( P < 0.001 ) , used gloves when placing an intravenous cannula ( P = 0.012 ) , intubation attempt within 30 s ( P < 0.04 ) , anaesthesia gas set at MAC at least 1 ( P < 0.04 ) , instructed anaesthetic nurse to keep SpO2 at least 95 % ( P < 0.05 ) , keep MAP at least 60 mmHg ( P < 0.05 ) , keep heart rate more than 50 beats per minute ( P < 0.002 ) , keep end-tidal pCO2 4–5.5 kPa ( P < 0.002 ) . Conclusion The simulation group performed better in 25 % of the tasks and similarly in the others compared with the traditional teaching group . With the same time and amount of teaching personnel we trained five or six students in the simulator compared with one student in the operating theatre . Further research will reveal whether these promising results with simulation may be applied more generally in anaesthesiology teaching to medical students The study objective was to vali date a flexible bronchoscopy simulator by determining if it could differentiate between expert and novice bronchoscopists . A subsequent evaluation phase was then done to determine whether use of the simulator would improve the rate of bronchoscopy skill acquisition for new pulmonary fellows . A multicenter prospect i ve cohort study was performed using a bronchoscopy simulator . Three cohorts were evaluated based on the number of bronchoscopies previously performed : " experts " ( > 500 , n = 9 ) , " intermediates " ( 25 to 500 , n = 8) , and " novices " ( none , n = 11 ) . Each participant performed two simulated cases with performance measures being recorded by the simulator . Performance measures that distinguished between groups were then used to evaluate the learning curve for new fellows training on the simulator . A r and omized-controlled trial was then conducted comparing the quality of bronchoscopy performance for new pulmonary fellows who were trained either with conventional methods or with the simulator . Expert bronchoscopists performed better on the simulator than intermediates who performed better than novices in terms of procedure time , percentage of segments visualized , time in red-out , and wall collisions . Training of new fellows demonstrated that after performing 20 bronchoscopic simulations , the skill level acquired with the simulator significantly improved in terms of speed , percentage of segments visualized , time in red-out , and collisions . Fellows trained on the simulator performed better than fellows trained using conventional methods during their first actual bronchoscopies as assessed by procedure time ( 815 versus 1,168 s , p = 0.001 ) , a bronchoscopy nurse 's subjective quality assessment score ( 7.7 + /- 0.3 versus 3.7 + /- 2.5 , p = 0.05 ) , and by a quantitative bronchoscopy quality score ( percentage of segments correctly identified/procedure time , 0.119 + /- 0.015 versus 0.046 + /- 034 , p = 0.03 ) . In conclusion , the bronchoscopy simulator was able to accurately assess bronchoscopy experience level . Training new fellows on the bronchoscopy simulator leads to more rapid acquisition of bronchoscopy expertise compared with conventional training methods . This technology has the potential to facilitate bronchoscopy training and to improve objective evaluations of bronchoscopy skills BACKGROUND : Pediatric housestaff are required to learn basic procedural skills and demonstrate competence during training . To our knowledge , an evidence d-based procedural skills curriculum does not exist . OBJECTIVE : To create , implement , and evaluate a modular procedural skills curriculum for pediatric residents . METHODS : A r and omized , controlled trial was performed . Thirty-eight interns in the Boston Combined Residency Program who began their training in 2005 were enrolled and r and omly assigned . Modules were created to teach residents bag-mask ventilation , venipuncture , peripheral intravenous catheter ( PIV ) insertion , and lumbar puncture skills . The curriculum was administered to participants in the intervention group during intern orientation . Interns in the control group learned procedural skills by usual methods . Subjects were evaluated by using a structured objective assessment on simulators immediately after the intervention and 7 months later . Success in performing live-patient procedures was self-reported by subjects . The primary outcome was successful performance of the procedure on the initial assessment . Secondary outcomes included checklist and knowledge examination scores , live-patient success , and qualitative assessment of the curriculum . RESULTS : Participants in the intervention group performed PIV placement more successfully than controls ( 79 % vs 35 % ) and scored significantly higher on the checklist for PIV placement ( 81 % vs 61 % ) and lumbar puncture ( 77 % vs 68 % ) at the initial assessment . There were no differences between groups at month 7 , and both groups demonstrated declining skills . There were no statistically significant differences in success on live-patient procedures . Those in the intervention group scored significantly higher on knowledge examinations . CONCLUSIONS : Participants in the intervention group were more successful performing certain simulated procedures than controls when tested immediately after receiving the curriculum but demonstrated declining skills thereafter . Future efforts must emphasize retraining , and residents must have sufficient opportunities to practice skills learned in a formal curriculum BACKGROUND Scenario-based training ( SBT ) with a computerized patient simulator ( CPS ) is effective in teaching physicians to manage high-risk , low-frequency events that are typical of critical care medicine . This study compares the initial airway management skills of a group of senior internal medicine residents trained using SBT with CPS during their first year of postgraduate training ( PGY ) with a group of senior internal medicine residents trained using the traditional experiential method . METHODS This was a prospect i ve , controlled trial that compared two groups of PGY3 internal medicine residents at an urban teaching hospital . One group ( n = 32 ) received training in initial airway management skills using SBT with CPS in their PGY1 ( ie , the simulation-trained [ ST ] group ) . The second group ( n = 30 ) received traditional residency training ( ie , the traditionally trained [ TT ] group ) . Each group was then tested during PGY3 in initial airway management skills using a st and ardized respiratory arrest scenario . RESULTS The ST group performed significantly better than the TT group in 8 of the 11 steps of the respiratory arrest scenario . Notable differences were found in the ability to attach a bag-valve mask ( BVM ) to high-flow oxygen ( ST group , 69 % ; TT group , 17 % ; p < 0.001 ) , correct insertion of oral airway ( ST group , 88 % ; TT group , 20 % ; p < 0.001 ) , and achieving an effective BVM seal ( ST group , 97 % ; TT group , 20 % ; p < 0.001 ) . CONCLUSIONS Traditional training consisting of 2 years of clinical experience was not sufficient to achieve proficiency in initial airway management skills , mostly due to inadequate equipment usage . This suggests that SBT with CPS is more effective in training medical residents than the traditional experiential method This study compared a graduated training programme with that of a traditional teaching method to facilitate the learning of the technique of fibreoptic nasotracheal intubation . Thirty-two anaesthesia trainees were r and omly assigned to two groups . The graduated programme involved : practice on a bronchoscopy teaching model ; exposure of the epiglottis and vocal cords in patients recovering from general anaesthesia ; performance of fibreoptic nasotracheal intubation in awake se date d patients . The traditional programme involved : demonstration ( on a patient ) of one fibreoptic nasotracheal intubation by the instructor ; performance of fibreoptic nasotracheal intubation ( by the trainee ) in awake se date d patients . Nasotracheal intubation was accomplished significantly more often by the trainees in the graduated programme ( 86 out of 96 ( 89.6 % ) v. 64 out of 96 ( 66.5 % ) ( P less than 0.01 ) . The results demonstrate that trainees who undergo a graduated training programme using simulators are initially more successful at awake fibreoptic nasotracheal intubation than those who have learned in the traditional manner , and that the conditions of the investigation were acceptable to the trainees and patients The pre-eminent requirement for surgical education is that it is effective and efficient . We sought to determine if the addition of low-fidelity simulation to our st and ard method of teaching cricothyroidotomy improves Postgraduate Year 1 residents ’ self-efficacy , knowledge , and skill to perform cricothyroidotomy . The teaching methods were st and ard education using a lecture and video compared with st and ard education plus low-fidelity simulation instruction and practice on a mannequin . The methods were r and omly assigned . After the assigned teaching in the morning and completion of pre- and posttests of self-efficacy and knowledge , the residents were evaluated on performance of cricothyroidotomy during the afternoon on euthanized swine . Time to complete the procedure and complications were recorded . Nineteen residents participated . Time to complete cricothyroidotomy was significantly less ( P = 0.047 ) and performance scores were significantly higher ( P = 0.01 ) in the simulation group . This group had four ( 36.4 % ) complications and the no simulation group had one ( 12.5 % ) complication ( P = 0.34 ) . Both groups improved on self-efficacy from pre- to posteducation ( P < 0.05 ) . Low-fidelity simulation can improve time and skill to perform cricothyroidotomy OBJECTIVES /HYPOTHESIS Flexible nasolaryngoscopy is an essential skill for otolaryngology trainees to develop , but there is a lack of st and ardized training for this procedure . The aim of this study was to assess whether using training on a realistic human mannequin together with structured video feedback improved trainees ' performance at flexible nasolaryngoscopy . STUDY DESIGN Three-armed , single-blinded , r and omized controlled study . METHODS Thirty-six junior doctors and final-year medical students were r and omly allocated to one of three groups . All received a lecture and video presentation on flexible nasolaryngoscopy . One group received additional tuition using a training mannequin . The last group received mannequin training and feedback on their performance using a video recording . The trainees then undertook flexible nasolaryngoscopy on volunteers with these endoscopies recorded . Blinded observers scored the trainees on a range of objective and subjective measures . The volunteers who were also blinded to the c and i date s ' training scored the comfort of the procedure . RESULTS Adding mannequin training showed a trend toward improvement of performance but did not reach statistical significance . Mannequin training together with video feedback produced significant performance improvement in patient comfort ( P = .0065 ) , time to reach the vocal folds ( P = .017 ) , and global ability ( P = .0006 ) . Inter-rater reliability was excellent with P < .01 in all assessment s. CONCLUSIONS Simulation-based training using an anatomically correct model of the upper airway together with formalized video-assisted feedback on that training is a simple and effective way to improve endoscopy skills prior to starting flexible nasolaryngoscopy on patients Background The availability of simulator technology at the University of Toronto ( Toronto , Ontario , Canada ) provided the opportunity to compare the efficacy of video-assisted and simulator-assisted learning . Methods After ethics approval from the University of Toronto , all final-year medical students were invited to participate in the current r and omized trial comparing video-based to simulator-based education using three scenarios . After an introduction to the simulator environment , a 5-min performance-based pretest was administered in the simulator operating room requiring management of a critical event . A posttest was administered after students had participated in either a faculty-facilitated video or simulator teaching session . St and ardized 12-point checklist performance protocol s were used for assessment purpose s. As well , students answered focused questions related to the educational sessions on a final examination . Student opinions regarding the value of the teaching sessions were obtained . Results One hundred forty-four medical students participated in the study ( scenario 1 , n = 43 ; scenario 2 , n = 48 ; scenario 3 , n = 53 ) . There was a significant improvement in posttest scores over pretest scores in all scenarios . There was no statistically significant difference in scores between simulator or video teaching methods . There were no differences in final examination marks when the two educational methods were compared . Student opinions indicated that the experiential simulator sessions were more enjoyable and valuable than the video teaching sessions . Conclusions Both simulator and video types of faculty-facilitated education offer a valuable learning experience . Future work is needed that addresses the long-term effects of experiential learning in the retention of knowledge and acquired skills Objectives To compare the effectiveness of training with an airway model simulator versus digital video disc (DVD)-based instruction in placement of double-lumen endotracheal ( DLT ) tubes by anaesthesiologists with limited thoracic experience . Design Single academic centre parallel r and omised controlled trial with computer-generated r and om allocation . Participants Sixty patients undergoing elective thoracic or oesophageal surgeries requiring one-lung ventilation . Twenty-seven non-thoracic anaesthesiologists were r and omised to place a DLT . Intervention DLT placement instruction by an interactive airway simulator or computer-based DVD training . The main outcome measure was successful DLT placement . Results Twenty-seven anaesthesiologists were r and omised to one of the two intervention groups . Sixty consecutive patients were assigned to a r and omised anaesthesiologist ( n = 30 in each group ) . Participants failed to correctly place or position the DLT tubes in 14 of 60 patients ( failure rate of 23 % ) . There was no difference in the probability of satisfactory placement or time for positioning of the DLT between the training groups ; 80.5 % ( 95 % confidence interval 58.2–96.2 % ) of tubes were successfully placed following intubation model simulator training versus 73.6 % ( 95 % confidence interval 49.8–88.5 % ) in the DVD group ( P = 0.378 ) . Conclusion Both teaching methods had similar outcomes for placement of DLTs by anaesthesiologists with limited thoracic anaesthesia experience . Both groups performed better than individuals in our prior study . Therefore , these methods should be considered when training anaesthesiologists to successfully place DLTs |
12,814 | 23,993,400 | This review will address the difficulty of non-invasive nodal staging , even with more advanced imaging techniques , and will show that surgical staging still finds a relatively high percentage of patients with intermediate- or high-risk prostate cancer that have microscopic tumor invasion in the pelvic nodes . | The role of elective radiotherapy of the pelvic nodal regions in clinical ly node-negative prostate cancer patients remains highly controversial . | Aim . To study whether use of neoadjuvant and rogen deprivation therapy ( N-ADT ) combined with whole pelvic radiotherapy ( WPRT ) for high-risk prostate cancer patients was associated with survival benefit over prostate radiotherapy ( PORT ) only . Material and Methods . Between 1999 and 2004 , 162 high-risk prostate cancer patients were treated with radiotherapy combined with long-term and rogen deprivation therapy ( L-ADT ) . Patients were prospect ively assigned into two groups : A ( N-ADT + WPRT + L-ADT ) n = 70 pts , B ( PORT + L-ADT ) n = 92 pts . Results . The 5-year actuarial overall survival ( OS ) rates were 89 % for A and 78 % for B ( P = .13 ) . The 5-year actuarial cause specific survival ( CSS ) rates were A = 90 % and B = 79 % ( P = .01 ) . Biochemical progression-free survival ( bPFS ) rates were 52 % versus 40 % ( P = .07 ) , for groups A and B , respectively . Conclusions . The WPRT combined with N-ADT compared to PORT for high-risk patients result ed in improvement in CSS and bPFS ; however no OS benefit was observed PURPOSE To evaluate survival and time to metastatic disease in patients treated for localized prostatic carcinoma in a Phase III radiotherapy ( RT ) protocol , Radiation Therapy Oncology Group ( RTOG ) 77 - 06 . Patients with T18N0M0 ( A2 ) or T2N0M0 ( B ) disease after lymphangiogram ( LAG ) or staging laparotomy ( SL ) were r and omized between prophylactic radiation to the pelvic lymph nodes and prostatic bed vs. prostatic bed alone . The outcome of both treatment arms , as well as a comparison of the LAG group , to that of the SL group , are up date d. METHODS AND MATERIAL S A total of 449 eligible males were entered into RTOG protocol 7706 between 1978 and 1983 . Lymph node staging was m and atory but at the physician 's discretion ; 117 ( 26 % ) patients had SL , while 332 ( 74 % ) had LAG . Follow-up was a median of 12 years and a maximum of 16 years . For those r and omized to receive prophylactic pelvic lymph nodal irradiation , 45 Gy of megavoltage RT was delivered via multiple portals in 4.5 - 5 weeks , while all patients received 65 Gy in 6.5 - 8 weeks to the prostatic bed . RESULTS There was no significant difference in survival whether treatment was administered to the prostate or prostate and pelvic lymph nodes . The SL group had greater 12-year survival than the LAG group ( 48 % vs. 38 % , p = 0.02 ) . Disease-free survival was statistically significant , with 38 % for the SL group vs. 26 % for the LAG group ( p = 0.003 ) . Bone metastasis was less common in the SL group ( 14 % ) than the LAG group ( 27 % ) ( p = 0.003 ) . CONCLUSION At 12-year median follow-up , there still was no survival difference in those patients treated prophylactically to the pelvic nodes and prostatic bed vs. the prostatic bed alone . Those patients not surgically staged with only LAG for lymph node evaluation were less accurately staged , as reflected by a statistically significant reduced survival and earlier metastases BACKGROUND Several trials evaluating the effect of prostate-specific antigen ( PSA ) testing on prostate-cancer mortality have shown conflicting results . We up date d prostate-cancer mortality in the European R and omized Study of Screening for Prostate Cancer with 2 additional years of follow-up . METHODS The study involved 182,160 men between the ages of 50 and 74 years at entry , with a predefined core age group of 162,388 men 55 to 69 years of age . The trial was conducted in eight European countries . Men who were r and omly assigned to the screening group were offered PSA-based screening , whereas those in the control group were not offered such screening . The primary outcome was mortality from prostate cancer . RESULTS After a median follow-up of 11 years in the core age group , the relative reduction in the risk of death from prostate cancer in the screening group was 21 % ( rate ratio , 0.79 ; 95 % confidence interval [ CI ] , 0.68 to 0.91 ; P=0.001 ) , and 29 % after adjustment for noncompliance . The absolute reduction in mortality in the screening group was 0.10 deaths per 1000 person-years or 1.07 deaths per 1000 men who underwent r and omization . The rate ratio for death from prostate cancer during follow-up years 10 and 11 was 0.62 ( 95 % CI , 0.45 to 0.85 ; P=0.003 ) . To prevent one death from prostate cancer at 11 years of follow-up , 1055 men would need to be invited for screening and 37 cancers would need to be detected . There was no significant between-group difference in all-cause mortality . CONCLUSIONS Analyses after 2 additional years of follow-up consoli date d our previous finding that PSA-based screening significantly reduced mortality from prostate cancer but did not affect all-cause mortality . ( Current Controlled Trials number , IS RCT N49127736 . ) PURPOSE To ascertain the reliability of computed tomography ( CT ) and CT-guided fine-needle aspiration biopsy ( FNAB ) in staging of lymph nodes in patients with locally confined prostatic carcinoma . MATERIAL S AND METHODS A total of 285 patients were studied prospect ively . FNAB was performed in 43 patients ( 15 % ) with lymph nodes suspect for metastasis on CT scans . FNAB findings were correlated with either the findings of the pathologic examination performed after lymph node dissection ( LND ) or the status of the lymph node at follow-up with CT after hormone therapy . RESULTS The sensitivity , specificity , and accuracy of CT-guided FNAB were 77.8 % , 100 % , and 96.5 % . If CT only had been performed , these results would have been 77.8 % , 96.7 % , and 93.7 % . CT staging was false-negative in only 10 patients , who had microscopic metastatic deposits in a solitary lymph node . CONCLUSION Combined CT and FNAB is highly efficient for assessment of lymph node metastasis . Therefore , it could be considered an alternative to surgical or laparoscopic lymphadenectomy in patients scheduled for radical prostatectomy or curative radiation therapy BACKGROUND The British Columbia r and omized radiation trial was design ed to determine the survival impact of locoregional radiation therapy in premenopausal patients with lymph node-positive breast cancer treated by modified radical mastectomy and adjuvant chemotherapy . Three hundred eighteen patients were assigned to receive no further therapy or radiation therapy ( 37.5 Gy in 16 fractions ) . Previous analysis at the 15-year follow-up showed that radiation therapy was associated with a statistically significant improvement in breast cancer survival but that improvement in overall survival was of only borderline statistical significance . We report the analysis of data from the 20-year follow-up . METHODS Survival was analyzed by the Kaplan-Meier method . Relative risk estimates were calculated by the Wald test from the proportional hazards regression model . All statistical tests were two-sided . RESULTS At the 20 year follow up ( median follow up for live patients : 249 months ) chemotherapy and radiation therapy , compared with chemotherapy alone , were associated with a statistically significant improvement in all end points analyzed , including survival free of isolated locoregional recurrences ( 74 % versus 90 % , respectively ; relative risk [ RR ] = 0.36 , 95 % confidence interval [ CI ] = 0.18 to 0.71 ; P = .002 ) , systemic relapse-free survival ( 31 % versus 48 % ; RR = 0.66 , 95 % CI = 0.49 to 0.88 ; P = .004 ) , breast cancer-free survival ( 48 % versus 30 % ; RR = 0.63 , 95 % CI = 0.47 to 0.83 ; P = .001 ) , event-free survival ( 35 % versus 25 % ; RR = 0.70 , 95 % CI = 0.54 to 0.92 ; P = .009 ) , breast cancer-specific survival ( 53 % versus 38 % ; RR = 0.67 , 95 % CI = 0.49 to 0.90 ; P = .008 ) , and , in contrast to the 15-year follow-up results , overall survival ( 47 % versus 37 % ; RR = 0.73 , 95 % CI = 0.55 to 0.98 ; P = .03 ) . Long-term toxicities , including cardiac deaths ( 1.8 % versus 0.6 % ) , were minimal for both arms . CONCLUSION For patients with high-risk breast cancer treated with modified radical mastectomy , treatment with radiation therapy ( schedule of 16 fractions ) and adjuvant chemotherapy leads to better survival outcomes than chemotherapy alone , and it is well tolerated , with acceptable long-term toxicity PURPOSE To investigate the relation between acute toxicity and irradiated volume in the organs at risk during three-dimensional conformal radiation therapy for prostate cancer . METHODS AND MATERIAL S From January to December 2001 , we treated 132 prostate cancer patients to a prescribed target dose of 70 Gy . Twenty-six patients ( 20 % ) received irradiation to the prostate only ( Group P ) , 86 patients ( 65 % ) had field arrangements encompassing the prostate and seminal vesicles ( Group PSV ) while 20 ( 15 % ) received modified pelvic fields ( Group MPF ) . A four-field conformal box technique was used . Acute toxicity according to the RTOG scoring system was prospect ively recorded throughout the course of treatment . RESULTS Overall , radiation was well tolerated with 11 % , 16 % and 35 % Grade 2 gastro-intestinal ( GI ) toxicity and 19 % , 34 % and 35 % Grade 2 or higher genito-urinary ( GU ) toxicity in Groups P , PSV and MPF , respectively . In univariate and multivariate analyses treatment group was a significant predictor for Grade 2 or higher acute morbidity . In multivariate logistic regression , the rectum dose-volume histogram parameters were correlated to the incidence of acute Grade 2 GI toxicity , with the fractional volumes receiving more than 37 - 40 Gy and above 70 Gy showing the statistically strongest correlation . The fractional bladder volume receiving more than 14 - 27 Gy showed the statistically strongest correlation with acute GU toxicity . CONCLUSIONS 3D-CRT radiation therapy to 70 Gy for prostate cancer was well tolerated . Only two of the 132 patients in the cohort experienced acute bladder toxicity Grade 3 , none had Grade 3 rectal toxicity . Uni- and multivariate analyses indicated that the volume treated was a significant factor for the incidence of Grade 2 or higher acute morbidity PURPOSE The Radiation Therapy Oncology Group ( RTOG ) 9413 trial demonstrated a better progression-free survival ( PFS ) with whole-pelvis ( WP ) radiotherapy ( RT ) compared with prostate-only ( PO ) RT . This secondary analysis was undertaken to determine whether " mini-pelvis " ( MP ; defined as > or = 10 x 11 cm but < 11 x 11 cm ) RT result ed in progression-free survival ( PFS ) comparable to that of WP RT . To avoid a timing bias , this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy ( N&CHT ) in Arms 1 and 2 of the study . METHODS AND MATERIAL S Eligible patients had a risk of lymph node ( LN ) involvement > 15 % . Neoadjuvant and concurrent hormonal therapy ( N&CHT ) was administered 2 months before and during RT for 4 months . From April 1 , 1995 , to June 1 , 1999 , a group of 325 patients were r and omized to WP RT + N&CHT and another group of 324 patients were r and omized to receive PO RT + N&CHT . Patients r and omized to PO RT were dichotomized by median field size ( 10 x 11 cm ) , with the larger field considered an " MP " field and the smaller a PO field . RESULTS The median PFS was 5.2 , 3.7 , and 2.9 years for WP , MP , and PO fields , respectively ( p = 0.02 ) . The 7-year PFS was 40 % , 35 % , and 27 % for patients treated to WP , MP , and PO fields , respectively . There was no association between field size and late Grade 3 + genitourinary toxicity but late Grade 3 + gastrointestinal RT complications correlated with increasing field size . CONCLUSIONS This subset analysis demonstrates that RT field size has a major impact on PFS , and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of > 15 % BACKGROUND The prostate component of the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial was undertaken to determine whether there is a reduction in prostate cancer mortality from screening using serum prostate-specific antigen ( PSA ) testing and digital rectal examination ( DRE ) . Mortality after 7 - 10 years of follow-up has been reported previously . We report extended follow-up to 13 years after the trial . METHODS A total of 76 685 men , aged 55 - 74 years , were enrolled at 10 screening centers between November 1993 and July 2001 and r and omly assigned to the intervention ( organized screening of annual PSA testing for 6 years and annual DRE for 4 years ; 38 340 men ) and control ( usual care , which sometimes included opportunistic screening ; 38 345 men ) arms . Screening was completed in October 2006 . All incident prostate cancers and deaths from prostate cancer through 13 years of follow-up or through December 31 , 2009 , were ascertained . Relative risks ( RRs ) were estimated as the ratio of observed rates in the intervention and control arms , and 95 % confidence intervals ( CIs ) were calculated assuming a Poisson distribution for the number of events . Poisson regression modeling was used to examine the interactions with respect to prostate cancer mortality between trial arm and age , comorbidity status , and pretrial PSA testing . All statistical tests were two-sided . RESULTS Approximately 92 % of the study participants were followed to 10 years and 57 % to 13 years . At 13 years , 4250 participants had been diagnosed with prostate cancer in the intervention arm compared with 3815 in the control arm . Cumulative incidence rates for prostate cancer in the intervention and control arms were 108.4 and 97.1 per 10 000 person-years , respectively , result ing in a relative increase of 12 % in the intervention arm ( RR = 1.12 , 95 % CI = 1.07 to 1.17 ) . After 13 years of follow-up , the cumulative mortality rates from prostate cancer in the intervention and control arms were 3.7 and 3.4 deaths per 10 000 person-years , respectively , result ing in a non-statistically significant difference between the two arms ( RR = 1.09 , 95 % CI = 0.87 to 1.36 ) . No statistically significant interactions with respect to prostate cancer mortality were observed between trial arm and age ( P(interaction ) = .81 ) , pretrial PSA testing ( P(interaction ) = .52 ) , and comorbidity ( P(interaction ) = .68 ) . CONCLUSIONS After 13 years of follow-up , there was no evidence of a mortality benefit for organized annual screening in the PLCO trial compared with opportunistic screening , which forms part of usual care , and there was no apparent interaction with age , baseline comorbidity , or pretrial PSA testing PURPOSE To assess the benefit and toxicity and quality -of-life ( QOL ) outcomes of pelvic nodes irradiation in nonmetastatic prostate carcinoma patients . PATIENTS AND METHODS Between December 1998 and June 2004 , 444 patients with T1b-T3 , N0 pNx , M0 prostate carcinoma were r and omly assigned to either pelvic and prostate radiotherapy or prostate radiotherapy only . Patients were stratified according to the prognostic factor of lymph node involvement ( LNI ) . Short-term 6-month neoadjuvant and concomitant hormonal therapy was allowed only for patients in the high-risk group . The pelvic dose was 46 Gy . The total dose recommended to the prostate was changed during the course of the study from 66 Gy to 70 Gy . Criteria for progression-free survival ( PFS ) included biologic prostate-specific antigen recurrences or a local or metastatic evolution . Acute and late toxicities were recorded according to the Radiation Therapy Oncology Group and Late Effects in Normal Tissues Subjective , Objective , Management , and Analytic scales , respectively . The QOL outcome was recorded with the European Organisation for Research and Treatment of Cancer Quality of Life Question naire C30 , the International Prostatic Symptom Score , and the Sexual Function Index scales . RESULTS With a 42.1-month median follow-up time , the 5-year PFS and overall survival were similar in the two treatment arms for the whole series and for each stratified group . On multivariate analysis , low LNI risk and hormonal therapy were statistically associated with increased PFS . However , subgroup analyses based on these factors did not show any benefit for pelvic irradiation . There were no significant differences in acute and late digestive toxicities and in QOL outcomes . CONCLUSION Pelvic node irradiation was well tolerated but did not improve PFS BACKGROUND In patients with prostate cancer who are deemed to be at intermediate or high risk of having nodal metastases , invasive diagnostic pelvic lymph-node dissection ( PLND ) is the gold st and ard for the detection of nodal disease . However , a new lymph-node-specific MR-contrast agent ferumoxtran-10 can detect metastases in normal-sized nodes ( ie , < 8 mm in size ) by use of MR lymphoangiography ( MRL ) . In this prospect i ve , multicentre cohort study , we aim ed to compare the diagnostic accuracy of MRL with up-to- date multidetector CT ( MDCT ) , and test the hypothesis that a negative MRL finding obviates the need for a PLND . METHODS We included consecutive patients with prostate cancer who had an intermediate or high risk ( risk of > 5 % according to routinely used nomograms ) of having lymph-node metastases . All patients were assessed by MDCT and MRL , and underwent PLND or fine-needle aspiration biopsy . Imaging results were correlated with histopathology . The primary outcomes were sensitivity , specificity , accuracy , NPV , and PPV of MRL and MDCT . This study is registered with Clinical Trials.gov , number NCT00185029 . FINDINGS The study was done in 11 hospitals in the Netherl and s between April 8 , 2003 , and April 19 , 2005 . 375 consecutive patients were included . 61 of 375 ( 16 % ) patients had lymph-node metastases . Sensitivity was 34 % ( 21 of 61 ; 95 % CI 23 - 48 ) for MDCT and 82 % ( 50 of 61 ; 70 - 90 ) for MRL ( McNemar 's test p<0.05 ) . Specificity was 97 % ( 303 of 314 ; 94 - 98 ) for MDCT and 93 % ( 291 of 314 ; 89 - 95 ) for MRL . Positive predictive value ( PPV ) was 66 % ( 21 of 32 ; 47 - 81 ) for MDCT and 69 % ( 50 of 73 ; 56 - 79 ) for MRL . Negative predictive value ( NPV ) was 88 % ( 303 of 343 ; 84 - 91 ) for MDCT and 96 % ( 291 of 302 ; 93 - 98 ) for MRL ( McNemar 's test p<0.05 ) . Of the 61 patients with lymph-node metastases , 50 were detected by MRL , of which 40 ( 80 % ) had metastases in normal-sized lymph nodes . The high sensitivity and NPV of MRL imply that in patients with a negative MRL , the chance of positive lymph nodes is less than 11/302 ( 4 % ) . INTERPRETATION MRL had significantly higher sensitivity and NPV than MDCT for patients with prostate cancer who had intermediate or high risk of having lymph-node metastases . In such patients , after a negative MRL , the post-test probability of having lymph-node metastases is low enough to omit a PLND PURPOSE To evaluate the results of selective nodal irradiation on basis of (18)F-deoxyglucose positron emission tomography ( PET ) scans in patients with limited-disease small-cell lung cancer ( LD-SCLC ) on isolated nodal failure . METHODS AND MATERIAL S A prospect i ve study was performed of 60 patients with LD-SCLC . Radiotherapy was given to a dose of 45 Gy in twice-daily fractions of 1.5 Gy , concurrent with carboplatin and etoposide chemotherapy . Only the primary tumor and the mediastinal lymph nodes involved on the pretreatment PET scan were irradiated . A chest computed tomography ( CT ) scan was performed 3 months after radiotherapy completion and every 6 months thereafter . RESULTS A difference was seen in the involved nodal stations between the pretreatment (18)F-deoxyglucose PET scans and computed tomography scans in 30 % of patients ( 95 % confidence interval , 20 - 43 % ) . Of the 60 patients , 39 ( 65 % ; 95 % confidence interval [ CI ] , 52 - 76 % ) developed a recurrence ; 2 patients ( 3 % , 95 % CI , 1 - 11 % ) experienced isolated regional failure . The median actuarial overall survival was 19 months ( 95 % CI , 17 - 21 ) . The median actuarial progression-free survival was 14 months ( 95 % CI , 12 - 16 ) . 12 % ( 95 % CI , 6 - 22 % ) of patients experienced acute Grade 3 ( Common Terminology Criteria for Adverse Events , version 3.0 ) esophagitis . CONCLUSION PET-based selective nodal irradiation for LD-SCLC result ed in a low rate of isolated nodal failures ( 3 % ) , with a low percentage of acute esophagitis . These findings are in contrast to those from our prospect i ve study of CT-based selective nodal irradiation , which result ed in an unexpectedly high percentage of isolated nodal failures ( 11 % ) . Because of the low rate of isolated nodal failures and toxicity , we believe that our data support the use of PET-based SNI for LD-SCLC PURPOSE Radiation Therapy Oncology Group protocol 85 - 31 was design ed to evaluate the effectiveness of adjuvant and rogen suppression , using goserelin , in unfavorable prognosis carcinoma of the prostate treated with definitive radiotherapy ( RT ) . METHODS AND MATERIAL S Eligible patients were those with palpable primary tumor extending beyond the prostate ( clinical Stage T3 ) or those with regional lymphatic involvement . Patients who had undergone prostatectomy were eligible if penetration through the prostatic capsule to the margin of resection and /or seminal vesicle involvement was documented histologically . Stratification was based on histologic differentiation , nodal status , acid phosphatase status , and prior prostatectomy . The patients were r and omized to either RT and adjuvant goserelin ( Arm I ) or RT alone followed by observation and application of goserelin at relapse ( Arm II ) . In Arm I , the drug was to be started during the last week of RT and was to be continued indefinitely or until signs of progression . RESULTS Between 1987 and 1992 , when the study was closed , 977 patients were entered : 488 to Arm I and 489 to Arm II . As of July 2003 , the median follow-up for all patients was 7.6 years and for living patients was 11 years . At 10 years , the absolute survival rate was significantly greater for the adjuvant arm than for the control arm : 49 % vs. 39 % , respectively ( p = 0.002 ) . The 10-year local failure rate for the adjuvant arm was 23 % vs. 38 % for the control arm ( p < 0.0001 ) . The corresponding 10-year rates for the incidence of distant metastases and disease-specific mortality was 24 % vs. 39 % ( p < 0.001 ) and 16 % vs. 22 % ( p = 0.0052 ) , respectively , both in favor of the adjuvant arm . CONCLUSION In a population of patients with unfavorable prognosis carcinoma of the prostate , and rogen suppression applied as an adjuvant after definitive RT was associated not only with a reduction in disease progression but in a statistically significant improvement in absolute survival . The improvement in survival appeared preferentially in patients with a Gleason score of 7 - 10 CONTEXT Clinical ly localized prostate cancer is very prevalent among US men , but recurrence after treatment with conventional radiation therapy is common . OBJECTIVE To evaluate the hypothesis that increasing the radiation dose delivered to men with clinical ly localized prostate cancer improves disease outcome . DESIGN , SETTING , AND PATIENTS R and omized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen ( PSA ) levels less than 15 ng/mL r and omized between January 1996 and December 1999 and treated at 2 US academic institutions . Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 ( range , 1.2 - 8.2 ) years . INTERVENTION Patients were r and omized to receive external beam radiation to a total dose of either 70.2 Gy ( conventional dose ) or 79.2 Gy ( high dose ) . This was delivered using a combination of conformal photon and proton beams . MAIN OUTCOME MEASURE Increasing PSA level ( ie , biochemical failure ) 5 years after treatment . RESULTS The proportions of men free from biochemical failure at 5 years were 78.8 % [ corrected ] ( 95 % confidence interval , 73.1%-84.6 % ) [ corrected ] for conventional-dose and 91.3 % [ corrected ] ( 95 % confidence interval , 87.2%-95.4 % ) [ corrected ] for high-dose therapy ( P<.001 ) , a 59 % [ corrected ] reduction in the risk of failure . The advantage to high-dose therapy was statistically significant [ corrected ] in both the low-risk subgroup [ corrected ] ( risk reduction , 84 % [ P<.001 ] ) [ corrected ] There has been no significant difference in overall survival rates between the treatment groups . Only 1 % of patients receiving conventional-dose and 2 % receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group ( RTOG ) grade 3 or greater . So far , only 2 % and 1 % , respectively , have experienced late morbidity of RTOG grade 3 or greater . CONCLUSIONS Men with clinical ly localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation . This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity PURPOSE We compared the results of extended ( obturator , hypogastric , common and external iliac nodes ) to modified ( obturator and hypogastric nodes only ) laparoscopic pelvic lymph node dissection in patients with clinical ly localized prostate cancer . MATERIAL S AND METHODS A total of 189 patients with stage T1 to T3 prostate cancer underwent modified ( 150 ) or extended ( 39 ) laparoscopic pelvic lymph node dissection for pelvic nodal assessment before definitive treatment . RESULTS Twice as many lymph nodes were removed via extended than modified laparoscopic pelvic lymph node dissection ( mean 17:8 versus 9.3 ) . The overall positivity rate was 23 of 189 lymph nodes ( 12.2 % ) , including 14 of 150 ( 7.3 % ) for modified and 9 of 39 ( 23.1 % ) for extended dissection ( p = 0.02 ) . Two patients ( 22 % ) who underwent extended dissection had positive lymph nodes in the external iliac area . Patients who presented with the high risk features of prostate specific antigen ( PSA ) greater than 20 ng./ml . , Gleason score 7 or greater , or stage T2b disease or greater had a 26.5 % ( p = 0.0002 ) , 22 % ( p = 0.0006 ) or 16.4 % ( p = 0.003 ) likelihood of positive lymph nodes , respectively . For extended versus modified laparoscopic pelvic lymph node dissection node positivity in high risk patients was 27 % versus 18.8 % ( p = 0.4 ) , 30 versus 26.4 % ( p = 0.8 ) and 25.4 versus 14.6 % ( p = 0.17 ) for Gleason score 7 or greater , PSA greater than 20 ng./ml . and disease stage T2b to T3a , respectively . Patients who underwent the extended procedure had a higher complication rate ( 35.9 versus 2 % , p < 0.0001 ) . No laparotomy was required . CONCLUSIONS Despite yielding a 2-fold higher node count and higher node positivity rate , extended laparoscopic pelvic lymph node dissection offers no advantage over modified laparoscopic pelvic lymph node dissection for diagnosing positive lymph nodes when results are analyzed by prognostic factors . The extended procedure is associated with a much higher complication rate . In patients with the high risk features of PSA greater than 20 ng./ml . , Gleason score 7 or greater and stage T2b to T3a disease modified laparoscopic pelvic lymph node dissection can be performed safely and effectively to help identify those who may benefit most from curative therapy PURPOSE To report the long-term results of a r and omized radiotherapy dose escalation trial for prostate cancer . METHODS AND MATERIAL S From 1993 to 1998 , a total of 301 patients with stage T1b to T3 prostate cancer were accrued to a r and omized external beam dose escalation trial using 70 Gy versus 78 Gy . The median follow-up is now 8.7 years . Kaplan-Meier analysis was used to compute rates of prostate-specific antigen ( PSA ) failure ( nadir + 2 ) , clinical failure , distant metastasis , disease-specific , and overall survival as well as complication rates at 8 years post-treatment . RESULTS For all patients , freedom from biochemical or clinical failure ( FFF ) was superior for the 78-Gy arm , 78 % , as compared with 59 % for the 70-Gy arm ( p = 0.004 , and an even greater benefit was seen in patients with initial PSA > 10 ng/ml ( 78 % vs. 39 % , p = 0.001 ) . The clinical failure rate was significantly reduced in the 78-Gy arm as well ( 7 % vs. 15 % , p = 0.014 ) . Twice as many patients either died of prostate cancer or are currently alive with cancer in the 70-Gy arm . Gastrointestinal toxicity of grade 2 or greater occurred twice as often in the high dose patients ( 26 % vs. 13 % ) , although genitourinary toxicity of grade 2 or greater was less ( 13 % vs. 8 % ) and not statistically significantly different . Dose-volume histogram analysis showed that the complication rate could be significantly decreased by reducing the amount of treated rectum . CONCLUSIONS Modest escalation in radiotherapy dose improved freedom from biochemical and clinical progression with the largest benefit in prostate cancer patients with PSA > 10 ng/ml BACKGROUND A r and omised phase-III trial compared external beam radiotherapy ( EBRT ) alone with EBRT combined with high-dose-rate brachytherapy boost ( HDR-BTb ) in localised prostate adenocarcinoma . METHODS From December 1997 to August 2005 , 218 patients were assigned to EBRT alone ( n=108 ) or EBRT followed by a temporary high-dose-rate implant ( n=110 ) . Patients were stratified according to tumour stage , PSA , Gleason score and and rogen deprivation therapy ( ADT ) . Biochemical/ clinical relapse-free survival ( RFS ) was the primary endpoint . Secondary endpoints were overall survival ( OS ) , urinary and bowel toxicity . RESULTS RFS was significantly higher in patients treated with EBRT+HDR-BTb ( log rank p=0.04 ) . In multivariate analysis treatment arm , risk category and ADT were significant covariates for risk of relapse . Differences in OS were not significant . Incidence of severe late urinary and bowel morbidity was similar . CONCLUSIONS EBRT+HDR-BTb result ed in a significant improvement in RFS compared to EBRT alone with a 31 % reduction in the risk of recurrence ( p=0.01 ) and similar incidence of severe late urinary and rectal morbidity PURPOSE Generally lymph node dissection is only considered a staging procedure for prostate cancer . Therefore , the need for meticulous lymph node dissection is often question ed and only sampling is suggested . We performed a prospect i ve study to identify the pattern of lymph node metastasis in prostate cancer and determine how extensive lymph node dissection must be not to under stage cases . MATERIAL S AND METHODS All patients with clinical ly organ confined prostate cancer , no prior hormonal treatment , negative preoperative staging computerized tomography and bone scan , who underwent radical prostatectomy between 1989 and 1999 , were evaluated prospect ively as to the number and location of lymph node metastasis . A meticulous lymph node dissection was performed along the external iliac vein , obturator nerve and internal iliac ( hypogastric ) vessels . Nodes from each location and side were su bmi tted separately for histological evaluation . RESULTS In 365 patients with a median serum prostate specific antigen of 11.9 ng./ml . ( range 0.4 to 172 ) the median number of nodes removed was 21 ( range 6 to 50 ) . Lymph nodes were positive in 88 ( 24 % ) patients and the median number of positive nodes was 2 ( range 1 to 19 ) . Internal iliac lymph nodes were positive in 51 ( 58 % ) of the 88 patients , including 34 with additional positive lymph nodes along the external iliac vein and /or obturator nerve . Internal iliac lymph nodes alone were positive in 17 ( 19 % ) of 88 patients . CONCLUSIONS There were significant numbers of lymph node metastases at all 3 different areas of lymphadenectomy . Positive lymph nodes were found along the internal iliac artery in more than half ( 58 % ) of the patients and exclusively in 19 % . Therefore , we consider lymph node dissection along the internal iliac ( hypogastric ) vessels essential for representative staging . Without this dissection a fifth of node positive cases would have been under staged and diseased nodes would have remained in more than half of the cases PURPOSE To determine whether a dose of 78 Gy improves outcome compared with a conventional dose of 68 Gy for prostate cancer patients treated with three-dimensional conformal radiotherapy . PATIENTS AND METHODS Between June 1997 and February 2003 , stage T1b-4 prostate cancer patients were enrolled onto a multicenter r and omized trial comparing 68 Gy with 78 Gy . Patients were stratified by institution , age , (neo)adjuvant hormonal therapy ( HT ) , and treatment group . Four treatment groups ( with specific radiation volumes ) were defined based on the probability of seminal vesicle involvement . The primary end point was freedom from failure ( FFF ) . Failure was defined as clinical failure or biochemical failure , according to the American Society of Therapeutic Radiation Oncology definition . Other end points were freedom from clinical failure ( FFCF ) , overall survival ( OS ) , and toxicity . RESULTS Median follow-up time was 51 months . Of the 669 enrolled patients , 664 were included in the analysis . HT was prescribed for 143 patients . FFF was significantly better in the 78-Gy arm compared with the 68-Gy arm ( 5-year FFF rate , 64 % v 54 % , respectively ) , with an adjusted hazard ratio of 0.74 ( P = .02 ) . No significant differences in FFCF or OS were seen between the treatment arms . There was no difference in late genitourinary toxicity of Radiation Therapy Oncology Group and European Organisation for Research and Treatment of Cancer grade 2 or more and a slightly higher nonsignificant incidence of late gastrointestinal toxicity of grade 2 or more . CONCLUSION This multicenter r and omized trial shows a significantly improved FFF in prostate cancer patients treated with a higher dose of radiotherapy Purpose Sentinel lymph node dissection ( SLND ) has replaced extended lymphadenectomy for nodal staging in several solid tumours . We present our results of SLND in prostate cancer in regard to detection and false-negative rate . Methods In a 2-day protocol about 300 MBq 99mTc-nanocolloid are injected into the prostate . Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes . During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist . The histological procedure includes haematoxylin and eosin staining , serial sections and immunohistochemistry . Results Since 1999 , a total of 2,020 men underwent SLND alone or in combination with either st and ard or extended lymphadenectomy after radical retropubic prostatectomy . Lymph nodes positive for metastases were found in 16.7 % of patients . The scintigraphic detection rate was 97.6 % and the intraoperative detection rate 98 % . For 187 lymph node-positive men who had either st and ard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated , result ing in false-negative findings in 11 of 187 patients ( 6 % ) . Conclusion Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging PURPOSE To evaluate the effect of whole pelvic radiotherapy ( WPRT ) in prostate cancer patients treated with RT and long-term ( > 1 year ) and rogen deprivation therapy ( ADT ) . METHODS AND MATERIAL S Prostate cancer patients with high-risk features ( Stage T3-T4 and /or Gleason score≥7 and /or prostate-specific antigen level≥20 ng/mL ) who had undergone RT and long-term ADT were included in the present analysis . Patients with bowel inflammatory disease , colon diverticula , and colon diverticulitis were excluded from WPRT and treated with prostate-only radiotherapy ( PORT ) . Patients were grouped according to nodal risk involvement as assessed by the Roach formula using different cutoff levels ( 15 % , 20 % , 25 % , and 30 % ) . Biochemical disease-free survival ( bDFS ) was analyzed in each group according to the RT type ( WPRT or PORT ) . RESULTS A total of 358 patients treated between 1994 and 2007 were included in the analysis ( 46.9 % with WPRT and 53.1 % with PORT ) . The median duration of ADT was 24 months ( range , 12 - 38 ) . With a median follow-up of 52 months ( range , 20 - 150 ) , the overall 4-year bDFS rate was 90.5 % . The 4-year bDFS rate was similar between the patients who had undergone WPRT or PORT ( 90.4 % vs. 90.5 % ; p = NS ) . However , in the group of patients with the greatest nodal risk ( > 30 % ) , a significant bDFS improvement was recorded for the patients who had undergone WPRT ( p=.03 ) . No differences were seen in acute toxicity among the patients treated with WPRT or PORT . The late gastrointestinal toxicity was similar in patients treated with PORT or WPRT ( p = NS ) . CONCLUSIONS Our analysis has supported the use of WPRT in association with long-term ADT for patients with high-risk nodal involvement ( > 30 % ) , although a definitive recommendation should be confirmed by a r and omized trial INTRODUCTION Recently , some controversy has arisen as to whether pelvic lymphadenectomy is still necessary for patients with prostate cancer who are undergoing radical prostatectomy . We prospect ively evaluated the results and morbidity of laparoscopic extended pelvic lymph node dissection in patients with high-risk prostate cancer defined as a serum prostate-specific antigen ( PSA ) level greater than 10 ng/mL or preoperative biopsy Gleason score of 7 or more . TECHNICAL CONSIDERATIONS In 123 consecutive patients with clinical ly organ-confined high-risk prostate cancer , laparoscopic extended pelvic lymphadenectomy was performed before laparoscopic radical prostatectomy . The boundaries of the pelvic lymph node dissection were the bifurcation of the common iliac artery superiorly , the node of Cloquet inferiorly , the external iliac vein laterally , and the bladder wall medially . Preparation was done with bipolar forceps and scissors , with meticulous coagulation of all lymphatic tissue . The mean PSA level was 14.8 ng/mL ( range 1.5 to 43.4 ) . The mean number of lymph nodes removed was 21 ( range 9 to 55 ) . A total of 21 patients ( 17 % ) had lymph node metastases . The overall complication rate was 4 % . CONCLUSIONS Laparoscopic extended pelvic lymph node dissection is safe and effective . The results and morbidity are equivalent to those of open surgery , with the advantage of a minimally invasive operative technique PURPOSE The goal of this project was to see if using IMRT to deliver elective pelvic nodal irradiation ( EPNI ) for prostate cancer reduced acute treatment toxicity . METHODS Two hundred and thirty patients were enrolled into prospect i ve trials delivering EPNI with a concomitant hypofractionated IMRT boost to the prostate . During accrual , the method of EPNI delivery changed as new literature emerged . Three methods were used ( 1 ) 4FB , ( 2 ) IMRT with 2 cm CTV margins around the pelvic vessels as suggested by Shih et al. ( 2005 ) [ 7 ] ( IMRT-Shih ) , and ( 3 ) IMRT with nodal volumes suggested by the RTOG ( IMRT-RTOG ) . Initially patients were treated with an empty bladder , with the remainder treated with bladder full . RESULTS Patients in the 4FB group had higher rates of grade 2 acute GI toxicities compared to the IMRT-Shih and IMRT-RTOG groups ( 31.9 % vs 20.8 % vs 7.2 % , p=0.0009 ) . Patients in the 4FB group had higher rates of grade 3 urinary frequency compared to the two IMRT groups ( 8.5 % vs 0 % vs 0 % , p=0.027 ) . However , multivariate analysis suggested the factor that most influenced toxicity was bladder filling followed by IMRT . CONCLUSIONS Bladder filling appeared to be the dominant factor which predicted for acute toxicity , followed by the use of IMRT PURPOSE To determine the impact of whole pelvic irradiation on the risk of PSA failure in prostate cancer patients , at high predicted risk for lymph node involvement , receiving definitive radiotherapy . MATERIAL S AND METHODS Between October 1987 and December 1995 , 506 patients with clinical ly localized prostate cancer were treated with definitive radiotherapy at UCSF and affiliated institutions . Treatment consisted of 4-field whole pelvic irradiation followed by a prostate-only boost , or prostate-only treatment ( median follow-up was 35 months and 30 months , respectively ) . PSA failure was defined as : 1 . a PSA value > or = 1 ng/ml ; or 2 . a PSA value that rose > or = 0.5 ng/ml in < or = 1 year posttreatment on two consecutive measurements , with the first rise defined as the time of failure . The calculated risk of lymph node positivity ( % rLN+ ) was defined as 2/3(iPSA ) + 10(GS-6 ) , and high risk was defined as % rLN+ > or = 15 % . Univariate and multivariate analyses were performed . RESULTS A total of 201 high-risk patients were identified . High-risk patients who received whole pelvic irradiation had significantly improved freedom from PSA failure compared to those who received prostate-only treatment ( median PFS = 34.3 months vs. 21.0 months ; p = 0.0001 ) . Potential confounding variables , including initial PSA , Gleason score , T stage , radiation dose , year of treatment , use of three-dimensional ( 3D ) conformal techniques , and use of hormone therapy , did not account for the observed difference in time to PSA failure . Multivariate analysis revealed type of radiation treatment to be the most significant independent predictor of outcome . CONCLUSION Whole pelvic radiotherapy significantly improves the PSA failure-free survival in patients with a high calculated risk of lymph node positivity BACKGROUND Controversy exists regarding the extent of pelvic lymph node dissection ( PLND ) in radical prostatectomy ( RP ) for prostate cancer . Impact of the extent of PLND may be determined by the disease risk . The aim of our study was to find the association between the extent of PLND on biochemical progression and disease risk . METHODS The study included 360 consecutive patients treated with RP for clinical ly localized prostate cancer at our department between 2000 and 2003 . Patients were r and omized to receive extended PLND ( n = 180 ) and st and ard PLND ( n = 180 ) at RP . Clinical and pathological data were prospect ively collected . The patients did not receive any neoadjuvant or adjuvant therapy . The relation of disease risk and the extent of PLND to biochemical progression-free survival ( BPFS ) were examined . RESULTS There were no significant differences in age , prostate-specific antigen , and other preoperative features in patients who underwent st and ard and extended PLND . Mean patient age was 68 y old and median follow-up was 74 mo . BPFS for the st and ard PLND group and the extended PLND group was 90.1 % and 91.3 % in low risk disease ( log rank P = 0.807 ) , 73.1 % and 85.7 % in intermediate risk disease ( log rank P = 0.042 ) , and 51.1 % and 71.4 % in high risk disease ( log rank P = 0.036 ) , respectively . In multivariate Cox proportional hazard analysis , extended PLND was an independent prognostic factor of biochemical progression-free survival when adjusting for other clinical and pathologic features . CONCLUSIONS In intermediate and high risk patients , extended PLND positively affects BPFS . In low risk patients , extended PLND may be omitted to reduce operation time and complications PURPOSE After publication of EORTC-22863 trial , prolonged and rogen deprivation therapy ( ADT ) combined with radiation therapy ( RT ) became st and ard policy for high-risk prostate cancer patients in British Columbia ( BC ) in 1997 . We evaluated whether population -based survival improved after this policy change . PATIENTS AND METHODS Two cohorts comprising all patients with T3-T4 prostate cancer treated with curative-intent RT in BC were review ed . The Early cohort ( n=730 ) was all patients treated between 1993 and 1995 , and the Late cohort ( n=584 ) was all patients treated between 1999 and 2001 . The BC Cancer Registry , which collects data on survival , was linked to RT and pharmacy data bases . Duration of ADT , age , stage , grade , presenting PSA , and Charlson comorbidity index ( CCI ; none=0 , minor=1 , major=2 + ) , were abstract ed from charts . RESULTS Usage of ≥6 months and ≥18 months of neoadjuvant and adjuvant ADT increased from 14 % and 1 % to 97 % and 59 % ( p<0.0001 ) . Baseline characteristics were similar , except for lower Gleason score ( G2 - 6 : 45 % vs. 20 % , G7 : 35 % vs. 48 % , G8 - 10 : 19 % vs. 32 % ; p<0.0001 ) , higher T-stage ( T4 : 9 % vs. 5 % , p=0.004 ) and higher comorbidity ( CCI 0 : 62 % vs. 71 % , CCI 1 : 26 % vs. 20 % , CCI 2 + : 11 % vs. 9 % , p=0.002 ) in the Early cohort . Disease-specific survival adjusted for competing risks from other causes mortality was improved ( 90 % vs. 86 % , p=0.042 ) . On multivariate analysis , the Late cohort was independently associated with improved 8-year overall survival ( 76 % vs. 64 % , p=0.0002 ) . CONCLUSIONS This population -based study demonstrated improved overall survival following a policy change to use of prolonged ADT with curative RT for patients with T3-T4 prostate cancer BACKGROUND AND PURPOSE High dose-rate ( HDR ) brachytherapy is most commonly administered as a boost in two or more fractions combined with external beam radiotherapy ( EBRT ) . Our purpose is to compare outcomes with a single fraction HDR boost to that with a st and ard fractionated boost in intermediate risk prostate cancer . MATERIAL S AND METHODS Results of two sequential phase II clinical trials are compared . The Single Fraction protocol consists of 15 Gy HDR in one fraction followed by 37.5 Gy EBRT in 15 fractions over 3 weeks ; the St and ard Fractionation protocol consisted of two HDR fractions each of 10 Gy , 1 week apart , followed by 45 Gy EBRT in 25 fractions . Patients had intermediate risk disease , and were well balanced for prognostic factors . Patients were followed prospect ively for efficacy , toxicity and health-related quality of life ( Exp and ed Prostate Index Composite ) . Efficacy was assessed biochemically using the Phoenix definition , and by biopsy at 2 years . RESULTS The Single Fraction protocol accrued 123 patients and the St and ard Fractionation protocol , 60 . With a median follow-up of 45 and 72 months , respectively , the biochemical disease-free survival was 95.1 % and 97.9 % in the Single and St and ard Fractionation trials ( p=0.3528 ) . Two-year prostate biopsy was positive in only 4 % and 8 % , respectively . There was no difference in late urinary or rectal toxicity rates , or in health-related quality of life between the two protocol s. CONCLUSIONS The Single Fraction HDR protocol results in high disease control rate and low toxicity similar to our previous protocol using two HDR insertions , with significant savings in re sources . While mature results with longer follow-up are awaited , a single 15 Gy may be considered as a st and ard fractionation regimen in combination with EBRT for men with intermediate risk disease Abstract Since 1970 , a total of 342 patients have received radical radiation therapy for carcinoma of the prostate . The estimated 5 year survival of 78 % and 5 year disease-free survival of 67 % remains unchanged . Initially , all patients received radiation therapy to the prostate . Recently , patients with more advanced disease as well as a selected group of patients with less extensive disease received extended field radiation to the pelvis . comparison of these two groups of patients shows no advantage for extended field radiation in early stage disease . However , in more advanced disease [ patients with involvement of more than one lobe or extraprostatic extension ] , there is evidence that extended field radiation improves the disease-free survival of these patients [ 63 % for 5 year disease free for extended field radiation versus 35 % for localized radiation ] . This difference persists irrespective of method of diagnosis . While this study is non-r and omized , the results were obtained during a period when there has been no other change in treatment philosophy . The results will require confirmation on a r and omized trial basis From 1978 to 1983 the Radiation Therapy Oncology Group conducted a study to evaluate the role of elective pelvic lymph node irradiation in carcinoma of the prostate . Eligible patients were those with clinical Stage A2 ( occult disease with more than 3 positive chips and poorly differentiated tumor ) and Stage B without clinical ( lymphangiogram ) or biopsy evidence of lymph node involvement . The patients were r and omized to receive 6.5 weeks of either prostatic bed irradiation only 6500 cGy at 180 - 200 cGy per treatment or pelvic node irradiation to 4500 cGy with a boost of 2000 cGy to the prostatic bed bringing the total dose to 6500 cGy . As of February , 1988 , the median follow up has been 7 years and there were 445 analyzable cases who were evaluated for local control , incidence of distant metastases , ned ( no evidence of disease ) survival and survival . The results of the study revealed no statistically significant benefit of elective pelvic irradiation BACKGROUND Irradiation after mastectomy can reduce locoregional recurrences in women with breast cancer , but whether it prolongs survival remains controversial . We conducted a r and omized trial of radiotherapy after mastectomy in high-risk premenopausal women , all of whom also received adjuvant systemic chemotherapy with cyclophosphamide , methotrexate , and fluorouracil ( CMF ) . METHODS A total of 1708 women who had undergone mastectomy for pathological stage II or III breast cancer were r and omly assigned to receive eight cycles of CMF plus irradiation of the chest wall and regional lymph nodes ( 852 women ) or nine cycles of CMF alone ( 856 women ) . The median length of follow-up was 114 months . The end points were locoregional recurrence , distant metastases , disease-free survival , and overall survival . RESULTS The frequency of locoregional recurrence alone or with distant metastases was 9 percent among the women who received radiotherapy plus CMF and 32 percent among those who received CMF alone ( P<0.001 ) . The probability of survival free of disease after 10 years was 48 percent among the women assigned to radiotherapy plus CMF and 34 percent among those treated only with CMF ( P<0.001 ) . Overall survival at 10 years was 54 percent among those given radiotherapy and CMF and 45 percent among those who received CMF alone ( P<0.001 ) . Multivariate analysis demonstrated that irradiation after mastectomy significantly improved disease-free survival and overall survival , irrespective of tumor size , the number of positive nodes , or the histopathological grade . CONCLUSIONS The addition of postoperative irradiation to mastectomy and adjuvant chemotherapy reduces locoregional recurrences and prolongs survival in high-risk premenopausal women with breast cancer PURPOSE Radiation Therapy Oncology Group ( RTOG ) 8610 was the first phase III r and omized trial to evaluate neoadjuvant and rogen deprivation therapy ( ADT ) in combination with external-beam radiotherapy ( EBRT ) in men with locally advanced prostate cancer . This report summarizes long-term follow-up results . MATERIAL S AND METHODS Between 1987 and 1991 , 456 assessable patients ( median age , 70 years ) were enrolled . Eligible patients had bulky ( 5 x 5 cm ) tumors ( T2 - 4 ) with or without pelvic lymph node involvement according to the 1988 American Joint Committee on Cancer TNM staging system . Patients received combined ADT that consisted of goserelin 3.6 mg every 4 weeks and flutamide 250 mg tid for 2 months before and concurrent with EBRT , or they received EBRT alone . Study end points included overall survival ( OS ) , disease-specific mortality ( DSM ) , distant metastasis ( DM ) , disease-free survival ( DFS ) , and biochemical failure ( BF ) . RESULTS Ten-year OS estimates ( 43 % v 34 % ) and median survival times ( 8.7 v 7.3 years ) favored ADT and EBRT , respectively ; however , these differences did not reach statistical significance ( P = .12 ) . There was a statistically significant improvement in 10-year DSM ( 23 % v 36 % ; P = .01 ) , DM ( 35 % v 47 % ; P = .006 ) , DFS ( 11 % v 3 % ; P < .0001 ) , and BF ( 65 % v 80 % ; P < .0001 ) with the addition of ADT , but no differences were observed in the risk of fatal cardiac events . CONCLUSION The addition of 4 months of ADT to EBRT appears to have a dramatic impact on clinical ly meaningful end points in men with locally advanced disease with no statistically significant impact on the risk of fatal cardiac events BACKGROUND The TROG 96.01 trial assessed whether 3-month and 6-month short-term neoadjuvant and rogen deprivation therapy ( NADT ) decreases clinical progression and mortality after radiotherapy for locally advanced prostate cancer . Here we report the 10-year results . METHODS Between June , 1996 , and February , 2000 , 818 men with T2b , T2c , T3 , and T4 N0 M0 prostate cancers were r and omly assigned to receive radiotherapy alone , 3 months of NADT plus radiotherapy , or 6 months of NADT plus radiotherapy . The radiotherapy dose for all groups was 66 Gy , delivered to the prostate and seminal vesicles ( excluding pelvic nodes ) in 33 fractions of 2 Gy per day ( excluding weekends ) over 6·5 - 7·0 weeks . NADT consisted of 3·6 mg goserelin given subcutaneously every month and 250 mg flutamide given orally three times a day . NADT began 2 months before radiotherapy for the 3-month NADT group and 5 months before radiotherapy for the 6-month NADT group . Primary endpoints were prostate-cancer-specific mortality and all-cause mortality . Treatment allocation was open label and r and omisation was done with a minimisation technique according to age , clinical stage , tumour grade , and initial prostate-specific antigen concentration ( PSA ) . Analysis was by intention-to-treat . The trial has been closed to follow-up and all main endpoint analyses are completed . The trial is registered with the Australian New Zeal and Clinical Trials Registry , number ACTRN12607000237482 . FINDINGS 802 men were eligible for analysis ( 270 in the radiotherapy alone group , 265 in the 3-month NADT group , and 267 in the 6-month NADT group ) after a median follow-up of 10·6 years ( IQR 6·9 - 11·6 ) . Compared with radiotherapy alone , 3 months of NADT decreased the cumulative incidence of PSA progression ( adjusted hazard ratio 0·72 , 95 % CI 0·57 - 0·90 ; p=0·003 ) and local progression ( 0·49 , 0·33 - 0·73 ; p=0·0005 ) , and improved event-free survival ( 0·63 , 0·52 - 0·77 ; p<0·0001 ) . 6 months of NADT further reduced PSA progression ( 0·57 , 0·46 - 0·72 ; p<0·0001 ) and local progression ( 0·45 , 0·30 - 0·66 ; p=0·0001 ) , and led to a greater improvement in event-free survival ( 0·51 , 0·42 - 0·61 , p<0·0001 ) , compared with radiotherapy alone . 3-month NADT had no effect on distant progression ( 0·89 , 0·60 - 1·31 ; p=0·550 ) , prostate cancer-specific mortality ( 0·86 , 0·60 - 1·23 ; p=0·398 ) , or all-cause mortality ( 0·84 , 0·65 - 1·08 ; p=0·180 ) , compared with radiotherapy alone . By contrast , 6-month NADT decreased distant progression ( 0·49 , 0·31 - 0·76 ; p=0·001 ) , prostate cancer-specific mortality ( 0·49 , 0·32 - 0·74 ; p=0·0008 ) , and all-cause mortality ( 0·63 , 0·48 - 0·83 ; p=0·0008 ) , compared with radiotherapy alone . Treatment-related morbidity was not increased with NADT within the first 5 years after r and omisation . INTERPRETATION 6 months of neoadjuvant and rogen deprivation combined radiotherapy is an effective treatment option for locally advanced prostate cancer , particularly in men without nodal metastases or pre-existing metabolic comorbidities that could be exacerbated by prolonged and rogen deprivation . FUNDING Australian Government National Health and Medical Research Council , Hunter Medical Research Institute , AstraZeneca , and Schering-Plough PURPOSE A great deal of controversy exists regarding the potential benefit of pelvic lymph node irradiation compared with treatment to the prostate only in patients with localized prostate cancer . Despite numerous reports , including a r and omized study , this issue has not been completely eluci date d. METHODS AND MATERIAL S A total of 963 patients with histologically proven localized adenocarcinoma of the prostate treated with definitive radiation therapy alone were analyzed . Median follow-up was 6.5 years ( minimum : 2 years , maximum : 22 years ) . Pelvic lymph nodes received 40 to 55 Gy with anteroposterior/posteroanterior and sometimes lateral stationary portals in 1.8 Gy daily fractions ; an additional dose was delivered to the prostate with 120 degrees bilateral are rotation to complete doses of 65 to 68 Gy for Stage A2 and B tumors and 68 to 71 Gy for Stage C tumors . The same total doses were delivered with smaller fields when the prostate only was treated . RESULTS In Stage A2 ( T1b , c ) the 10-year clinical pelvic failure rate was 16 % regardless of the volume irradiated or tumor differentiation . With Stage B ( T2 ) well- or moderately differentiated tumors , the 10-year pelvic failure rates were 22 % when pelvic lymph nodes were irradiated and 32 % when prostate only was irradiated ( p = 0.41 ) . With Stage A2 ( T1b , c ) and B ( T2 ) poorly differentiated tumors , the 10-year pelvic failure rates were 32 % and 7 % , respectively ( p = 0.72 ) . With clinical stage C ( T3 ) well-differentiated tumors treated with 50 to 55 Gy to pelvic lymph nodes , the pelvic failure rate was 22 % compared with 37 % in those receiving 40 to 45 Gy ( p < or = 0.07 ) . A significant reduction in pelvic failures was noted with Stage C poorly differentiated tumors when the pelvic lymph nodes received doses higher than 50 Gy ( 23 % ) compared with lower doses ( 46 % ) ( p < or = 0.01 ) . Volume or doses of irradiation did not influence incidence of distant metastases in any stage or tumor differentiation group . Disease-free survival did not correlate with volume treated in any clinical stage or tumor differentiation group . In 317 patients on whom pretreatment prostate-specific antigen levels were available , there is a suggestion that those treated to the pelvic lymph nodes had a higher chemical disease-free survival than those receiving prostate irradiation only . Follow-up is short , and differences are not statistically significant in any of the groups . Morbidity of therapy was slightly higher in patients treated to the pelvic lymph nodes , but in Stages A2 ( T1b , c ) and B ( T2 ) differences are not statistically significant ( 4 to 6 % ) . Stage C patients treated to the pelvic lymph nodes with 50 Gy had a 12 % incidence of Grade 2 rectosigmoid morbidity compared with 6 % in those treated with 40 Gy ( p = 0.26 ) . CONCLUSIONS In this retrospective analysis , pelvic lymph node irradiation did not influence local/pelvic tumor control , incidence of distant metastases , or disease-free survival in patients with clinical Stage A2 ( T1b , c ) or B ( T2 ) localized carcinoma of the prostate . In patients with Stage C ( T3 ) disease , irradiation of the pelvic lymph nodes with doses of 50 to 55 Gy result ed in a lower incidence of pelvic recurrences and improved disease-free survival . Morbidity of therapy was acceptable , although patients with Stage C disease had a somewhat higher incidence of Grade 2 rectosigmoid morbidity . Pelvic lymph node irradiation is being eluci date d in properly design ed prospect i ve , r and omized protocol PURPOSE To up date the effect of immediate and rogen suppression in conjunction with st and ard external-beam irradiation versus radiation alone on a group of histologically lymph node-positive patients with adenocarcinoma of the prostate . MATERIAL S AND METHODS A national prospect i ve r and omized trial ( Radiation Therapy Oncology Group 85 - 31 ) of st and ard external-beam irradiation plus immediate and rogen suppression versus external-beam irradiation alone was initiated in 1985 for patients with locally advanced adenocarcinoma of the prostate . One hundred seventy-three patients in this trial had histologically involved lymph nodes . Ninety-eight patients received radiation plus immediate and rogen suppression ( luteinizing hormone-releasing hormone [ LHRH ] agonist ) , whereas 75 patients received radiation alone with hormonal manipulation instituted at the time of relapse . RESULTS With a median follow-up of 6.5 years for all patients and 9.5 years for living patients , estimated progression-free survival with prostate-specific antigen ( PSA ) level less than 1.5 ng/mL at 5 and 9 years was 54 % and 33 % , respectively , for patients who received immediate LHRH agonist versus 10 % [ corrected ] and 4 % for patients who received radiation alone with hormonal manipulation instituted at time of relapse ( P < .0001 ) . Multivariate analysis revealed radiation therapy and immediate hormonal manipulation as having a statistically significant impact on all end points analyzed : absolute survival , disease-specific failure , metastatic failure , and biochemical control with PSA less than 4 ng/mL and less than 1.5 ng/mL. CONCLUSION Pending the results of r and omized trials , patients with adenocarcinoma of the prostate who have pathologically involved pelvic lymph nodes ( pathologic node-positive or clinical stage D1 ) should be considered for external-beam irradiation plus immediate hormonal manipulation rather than radiation alone with hormone manipulation at the time of relapse PURPOSE This trial was design ed to test the hypothesis that total and rogen suppression and whole pelvic radiotherapy ( WPRT ) followed by a prostate boost improves progression-free survival ( PFS ) by > or = 10 % compared with total and rogen suppression and prostate only RT ( PORT ) . This trial was also design ed to test the hypothesis that neoadjuvant hormonal therapy ( NHT ) followed by concurrent total and rogen suppression and RT improves PFS compared with RT followed by adjuvant hormonal therapy ( AHT ) by > or = 10 % . METHODS AND MATERIAL S Patients eligible for the study included those with clinical ly localized adenocarcinoma of the prostate and an elevated prostate-specific antigen level of < 100 ng/mL. Patients were stratified by T stage , prostate-specific antigen level , and Gleason score and were required to have an estimated risk of lymph node involvement of > 15 % . RESULTS The difference in overall survival for the four arms was statistically significant ( p = 0.027 ) . However , no statistically significant differences were found in PFS or overall survival between NHT vs. AHT and WPRT compared with PORT . A trend towards a difference was found in PFS ( p = 0.065 ) in favor of the WPRT + NHT arm compared with the PORT + NHT and WPRT + AHT arms . CONCLUSIONS Unexpected interactions appear to exist between the timing of hormonal therapy and radiation field size for this patient population . Four Phase III trials have demonstrated better outcomes when NHT was combined with RT compared with RT alone . The Radiation Therapy Oncology Group 9413 trial results have demonstrated that when NHT is used in conjunction with RT , WPRT yields a better PFS than does PORT . It also showed that when NHT + WPRT results in better overall survival than does WPRT + short-term AHT . Additional studies are warranted to determine whether the failure to demonstrate an advantage for NHT + WPRT compared with PORT + AHT is chance or , more likely , reflects a previously unrecognized biologic phenomenon CONTEXT Comorbidities may increase the negative effects of specific anticancer treatments such as and rogen suppression therapy ( AST ) . OBJECTIVES To compare 6 months of AST and radiation therapy ( RT ) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality . DESIGN , SETTING , AND PATIENTS At academic and community-based medical centers in Massachusetts , between December 1 , 1995 , and April 15 , 2001 , 206 men with localized but unfavorable-risk prostate cancer were r and omized to receive RT alone or RT and AST combined . All-cause mortality estimates stratified by r and omized treatment group and further stratified in a postr and omization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test . MAIN OUTCOME MEASURE Time to all-cause mortality . RESULTS As of January 15 , 2007 , with a median follow-up of 7.6 ( range , 0.5 - 11.0 ) years , 74 deaths have occurred . A significant increase in the risk of all-cause mortality ( 44 vs 30 deaths ; hazard ratio [ HR ] , 1.8 ; 95 % confidence interval [ CI ] , 1.1 - 2.9 ; P = .01 ) was observed in men r and omized to RT compared with RT and AST . However , the increased risk in all-cause mortality appeared to apply only to men r and omized to RT with no or minimal comorbidity ( 31 vs 11 deaths ; HR , 4.2 ; 95 % CI , 2.1 - 8.5 ; P < .001 ) . Among men with moderate or severe comorbidity , those r and omized to RT alone vs RT and AST did not have an increased risk of all-cause mortality ( 13 vs 19 deaths ; HR , 0.54 ; 95 % CI , 0.27 - 1.10 ; P = .08 ) . CONCLUSIONS The addition of 6 months of AST to RT result ed in increased overall survival in men with localized but unfavorable-risk prostate cancer . This result may pertain only to men without moderate or severe comorbidity , but this requires further assessment in a clinical trial specifically design ed to assess this interaction . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00116220 |
12,815 | 27,637,288 | The complication rate was significantly lower with endosonographic procedures .
Endoscopic ultrasound-guided fine needle aspiration/endobronchial ultrasound-guided transbronchial needle aspiration was found to have similar yield but lower complication rate compared to mediastinoscopy in the initial mediastinal staging of non-small cell lung cancer | Whether endosonography can replace mediastinoscopy as the initial procedure for mediastinal staging of non-small cell lung cancer remains controversial . | Because the clinics in a multiclinic r and omized clinical trial represent neither fixed stratification effects nor r and om classificatory effects , the appropriate analysis of data from such a trial has been the subject of controversy and debate . The following are some of the elements of controversy that are discussed and for which some bases for resolution are proposed . Is it ever valid to ignore the effects of clinics in the analysis ? Is it ever valid to drop clinics from the analysis ? Is a multiclinic clinical trial similar in structure or not to a single-clinic clinical trial in which patients have been stratified on a classificatory factor ? Assuming that clinics will be taken account of in the analysis , should it be the weighted or the unweighted average of within-clinic treatment differences that is to be taken as the best estimate of the overall difference between the treatments ? How should the data be analyzed if there is evidence of treatment-by-clinic interaction CONTEXT Up to 40 % of thoracotomies performed for non-small cell lung cancer are unnecessary , predominantly due to inaccurate preoperative detection of lymph node metastases and mediastinal tumor invasion ( T4 ) . Mediastinoscopy and the novel , minimally invasive technique of transesophageal ultrasound-guided fine-needle aspiration ( EUS-FNA ) target different mediastinal lymph node stations . In addition , EUS can identify tumor invasion in neighboring organs if tumors are located adjacent to the esophagus . OBJECTIVE To investigate the additional value of EUS-FNA to mediastinoscopy in the preoperative staging of patients with non-small cell lung cancer . DESIGN , SETTING , AND PATIENTS Prospect i ve , nonr and omized multicenter trial performed in 1 referral and 5 general hospitals in the Netherl and s. During a 3-year period ( 2000 - 2003 ) , 107 consecutive patients with potential resectable non-small cell lung cancer underwent preoperative staging by both EUS-FNA and mediastinoscopy . Patients underwent thoracotomy with tumor resection if mediastinoscopy was negative . Surgical-pathological staging was compared with preoperative findings and the added benefit of the combined strategy was assessed . INTERVENTION The EUS-FNA examination was performed as an additional staging test to mediastinoscopy in all patients . MAIN OUTCOME MEASURE Detection of mediastinal tumor invasion ( T4 ) and lymph node metastases ( N2/N3 ) comparing the combined staging by both EUS-FNA and mediastinoscopy with staging by mediastinoscopy alone . RESULTS The combination of EUS-FNA and mediastinoscopy identified more patients with tumor invasion or lymph node metastases ( 36 % ; 95 % confidence interval [ CI ] , 27%-46 % ) compared with either mediastinoscopy alone ( 20 % ; 95 % CI , 13%-29 % ) or EUS-FNA ( 28 % ; 95 % CI , 19%-38 % ) alone . This indicated that 16 % of thoracotomies could have been avoided by using EUS-FNA in addition to mediastinoscopy . However , 2 % of the EUS-FNA findings were false-positive . CONCLUSION These preliminary findings suggest that EUS-FNA , when added to mediastinoscopy , improves the preoperative staging of lung cancer due to the complementary reach of EUS-FNA in detecting mediastinal lymph node metastases and the ability to assess mediastinal tumor invasion CONTEXT Mediastinal nodal staging is recommended for patients with resectable non-small cell lung cancer ( NSCLC ) . Surgical staging has limitations , which results in the performance of unnecessary thoracotomies . Current guidelines acknowledge minimally invasive endosonography followed by surgical staging ( if no nodal metastases are found by endosonography ) as an alternative to immediate surgical staging . OBJECTIVE To compare the 2 recommended lung cancer staging strategies . DESIGN , SETTING , AND PATIENTS R and omized controlled multicenter trial ( Ghent , Leiden , Leuven , Papworth ) conducted between February 2007 and April 2009 in 241 patients with resectable ( suspected ) NSCLC in whom mediastinal staging was indicated based on computed or positron emission tomography . INTERVENTION Either surgical staging or endosonography ( combined transesophageal and endobronchial ultrasound [ EUS-FNA and EBUS-TBNA ] ) followed by surgical staging in case no nodal metastases were found at endosonography . Thoracotomy with lymph node dissection was performed when there was no evidence of mediastinal tumor spread . MAIN OUTCOME MEASURES The primary outcome was sensitivity for mediastinal nodal ( N2/N3 ) metastases . The reference st and ard was surgical pathological staging . Secondary outcomes were rates of unnecessary thoracotomy and complications . RESULTS Two hundred forty-one patients were r and omized , 118 to surgical staging and 123 to endosonography , of whom 65 also underwent surgical staging . Nodal metastases were found in 41 patients ( 35 % ; 95 % confidence interval [ CI ] , 27%-44 % ) by surgical staging vs 56 patients ( 46 % ; 95 % CI , 37%-54 % ) by endosonography ( P = .11 ) and in 62 patients ( 50 % ; 95 % CI , 42%-59 % ) by endosonography followed by surgical staging ( P = .02 ) . This corresponded to sensitivities of 79 % ( 41/52 ; 95 % CI , 66%-88 % ) vs 85 % ( 56/66 ; 95 % CI , 74%-92 % ) ( P = .47 ) and 94 % ( 62/66 ; 95 % CI , 85%-98 % ) ( P = .02 ) . Thoracotomy was unnecessary in 21 patients ( 18 % ; 95 % CI , 12%-26 % ) in the mediastinoscopy group vs 9 ( 7 % ; 95 % CI , 4%-13 % ) in the endosonography group ( P = .02 ) . The complication rate was similar in both groups . CONCLUSIONS Among patients with ( suspected ) NSCLC , a staging strategy combining endosonography and surgical staging compared with surgical staging alone result ed in greater sensitivity for mediastinal nodal metastases and fewer unnecessary thoracotomies . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00432640 Introduction : Correct mediastinal staging is critical for determination of the most appropriate management strategy in patients with non – small-cell lung cancer ( NSCLC ) . The purpose of this study was to compare the diagnostic performance of endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) with that of mediastinoscopy in patients with NSCLC . Methods : A prospect i ve trial was conducted in a tertiary referral center in Korea . Patients with histologically proven NSCLC and suspicion for N1 , N2 , or N3 metastasis were enrolled . Each patient underwent EBUS-TBNA followed by mediastinoscopy . Surgical resection and complete lymph node dissection were conducted in patients for whom no evidence of mediastinal metastasis was apparent after mediastinoscopy . Results : In total , 138 patients underwent EBUS-TBNA and 127 completed both EBUS-TBNA and mediastinoscopy . N2/N3 disease was confirmed in 59.1 % of the patients . The diagnostic sensitivity , specificity , accuracy , positive predictive value , and negative predictive value ( NPV ) of EBUS-TBNA on a per-person analysis were 88.0 % , 100 % , 92.9 % , 100 % , and 85.2 % , respectively . The diagnostic sensitivity , specificity , accuracy , positive predictive value , and NPV of mediastinoscopy on a per-person analysis were 81.3 % , 100 % , 89.0 % , 100 % , and 78.8 % , respectively . Significant differences in the sensitivity , accuracy , and NPV were evident between EBUS-TBNA and mediastinoscopy ( p < 0.005 ) . Conclusions : EBUS-TBNA was superior to mediastinoscopy in terms of its diagnostic performance for mediastinal staging of cN1–3 NSCLC . Because EBUS-TBNA is both less invasive and affords superior diagnostic sensitivity , it should be the first-line procedure performed in patients with NSCLC BACKGROUND Exact mediastinal evaluation of patients with non-small-cell lung cancer ( NSCLC ) is m and atory to improve selection of resectable and curable patients for surgery . Mediastinoscopy ( MS ) and endoscopic ultrasound guided fine needle aspiration biopsy ( EUS-FNA ) are considered complementary , MS covering the anterior- and EUS-FNA the posterior mediastinum . Both methods can reach the paratracheal- and subcarinal-regions , but little is known about which method is most accurate , when compared in patients having both procedures performed . The aim of this study was to assess and compare the diagnostic value of MS and EUS-FNA with regard to mediastinal malignancy in the paratracheal- and subcarinal-regions . METHODS Sixty patients considered to be potential c and i date s for resection of verified or suspected NSCLC underwent MS and EUS-FNA . The EUS-FNA diagnoses were confirmed either by open thoracotomy , MS or clinical follow-up . RESULTS MS and EUS-FNA were conclusive for paratracheal or subcarinal mediastinal disease in 6 and 24 patients , respectively . Two patients with N2 disease diagnosed by EUS-FNA were upstaged to N3 by MS . The sensitivity for lymph node metastases in the right paratracheal region ( 2/4R ) was 67 % for EUS-FNA versus 33 % for MS ( p=0.69 ) . In the left paratracheal region ( 2/4L ) the sensitivity of EUS-FNA was 80 % versus 33 % for MS ( p=0.06 ) . In the subcarinal region ( 7 ) the sensitivity of EUS-FNA was 100 % versus 7 % for MS ( p<0.01 ) . The sensitivity for lymph node metastases in region 2/4L and /or 2/4R and /or 7 was 96 % for EUS-FNA versus 24 % for MS ( p<0.01 ) . CONCLUSION In our h and s EUS-FNA was superior to MS in the examination of paratracheal- and subcarinal-regions of patients considered for resection of lung cancer RATIONALE Data about the influence of the type of sedation on yield , complications , and tolerance of endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) are based mostly on retrospective studies and are largely inconsistent . OBJECTIVES To determine whether the type of sedation influences the diagnostic yield of EBUS-TBNA , its complication rates , and patient tolerance . METHODS Patients referred for EBUS-TBNA were r and omized ( 1:1 ) to undergo this procedure under general anesthesia ( GA ) or moderate sedation ( MS ) . Pathologists were blinded to group allocation . MEASUREMENTS AND MAIN RESULTS The main outcome was " diagnostic yield , " defined as the percentage of patients for whom EBUS-TBNA rendered a specific diagnosis . One hundred and forty-nine patients underwent EBUS-TBNA , 75 under GA and 74 under MS . Demographic and baseline clinical characteristics were well balanced . Two hundred and thirty-six lymph nodes ( LNs ) and six masses were sample d in the GA group ( average , 3.2 ± 1.9 sites/patient ) , and 200 LNs and six masses in the MS group ( average , 2.8 ± 1.5 sites/patient ) ( P = 0.199 ) . The diagnostic yield was 70.7 % ( 53 of 75 ) and 68.9 % ( 51 of 74 ) for the GA group and MS group , respectively ( P = 0.816 ) . The sensitivity was 98.2 % in the GA group ( confidence interval , 97 - 100 % ) and 98.1 % in the MS group ( confidence interval , 97 - 100 % ) ( P = 0.979 ) . EBUS was completed in all patients in the GA group , and in 69 patients ( 93.3 % ) in the MS group ( P = 0.028 ) . There were no major complications or escalation of care in either group . Minor complications were more common in the MS group ( 29.6 vs. 5.3 % ) ( P < 0.001 ) . Most patients stated they " definitely would " undergo this procedure again in both groups ( P = 0.355 ) . CONCLUSIONS EBUS-TBNA performed under MS results in comparable diagnostic yield , rate of major complications , and patient tolerance as under GA . Future prospect i ve multicenter studies are required to corroborate our findings . Clinical trial registered with www . clinical trials.gov ( NCT 01430962 ) BACKGROUND It is unclear whether endoscopic mediastinal lymph node ( LN ) staging techniques are equivalent to surgical mediastinal staging ( SMS ) techniques in patients with potentially operable non-small cell lung cancer ( NSCLC ) . METHODS A total of 166 patients with confirmed or suspected NSCLC who required SMS based on current guidelines were enrolled in this prospect i ve controlled trial comparing endosonographic mediastinal LN staging with SMS . Each patient served as his or her own control . All patients underwent endobronchial ultrasound ( EBUS ) , endoscopic ultrasound ( EUS ) , and SMS during a single procedure . Results of EBUS , EUS , and combined EBUS/EUS were compared with SMS ( gold st and ard ) and in patients with negative LN staging results , with LN sampling at pulmonary resection . RESULTS EBUS , EUS , combined EBUS/EUS , and SMS sample d a mean of 2.2 , 1.7 , 3.9 , and 3.1 LN stations , respectively . The prevalence of mediastinal nodal disease ( N2/N3 ) was 32 % ( 53 of 166 patients ) . The sensitivity , negative predictive value , and diagnostic accuracy of the endoscopic staging modalities , respectively , were EBUS , 72 % ( 95 % CI , 0.58 - 0.83 ) , 88 % ( 0.81 - 0.93 ) , and 91 % ( 0.85 - 0.95 ) ; EUS , 62 % ( 0.48 - 0.75 ) , 85 % ( 0.78 - 0.91 ) , and 88 % ( 0.82 - 0.92 ) ; and combined EBUS/EUS , 91 % ( 0.79 - 0.97 ) , 96 % ( 0.90 - 0.99 ) , and 97 % ( 0.93 - 0.99 ) . Endosonography was diagnostic for N2/N3/M1 disease in 24 patients in whom SMS findings were negative , preventing futile thoracotomy in an additional 14 % of patients . CONCLUSIONS The combined EBUS/EUS procedure can replace surgical mediastinal staging in patients with potentially resectable NSCLC . Additionally , endosonography leads to improved staging compared with SMS because it allows the biopsy of LNs and metastases unattainable with SMS techniques . TRIAL REGISTRY Clinical Trials.gov ; No. : NCT01011595 ; URL : www . clinical trials.gov RATIONALE Assessment of mediastinal lymph nodes is recommended in patients with non-small cell lung cancer without distant metastases . Linear transesophageal endoscopic ultrasound with real-time guided fine-needle aspiration ( EUS-FNA ) is a promising , nonsurgical tool for mediastinal staging . OBJECTIVES We conducted a r and omized controlled trial comparing surgical staging with EUS-FNA . METHODS Patients with proven or suspected non-small cell lung cancer in whom mediastinal exploration was required were r and omly assigned to undergo EUS-FNA or the appropriate surgical staging procedure . When EUS-FNA did not show malignant lymph node invasion , a confirmatory surgical staging procedure was done . A negative surgical staging procedure was followed by thoracotomy with systematic lymph node sampling . The primary endpoint was the rate of surgical staging interventions . The secondary endpoints were test performance of EUS-FNA and surgical staging , morbidity , and length of hospital stay , considering surgical staging was performed as an in-patient procedure . MEASUREMENTS AND MAIN RESULTS A total of 40 patients were r and omized : 19 to EUS-FNA , and 21 to surgical mediastinal staging . Patient and tumor characteristics were well balanced between both groups . For patients allocated to EUS-FNA , surgical staging was needed in 32 % ( P < 0.001 ) . The sensitivity to detect malignant lymph node invasion was 93 % ( 95 % confidence interval , 66 - 99 % ) for EUS-FNA and 73 % ( 95 % confidence interval , 39 - 93 % ) for surgical staging ( P = 0.29 ) . Complication rate was 0 % for EUS-FNA and 5 % for surgical staging ( P = 1.0 ) . The median hospital stay was significantly shorter for EUS-FNA than for surgical staging ( 0 vs. 2 nights ; P < 0.001 ) . CONCLUSIONS EUS-FNA reduces the need for surgical staging procedures in patients with ( suspected ) lung cancer in whom a mediastinal exploration is needed Background : Real-time endobronchial ultrasound has increased the accuracy of conventional transbronchial needle aspiration biopsy in sampling mediastinal lymph nodes . Nevertheless , direct comparisons with mediastinoscopy are not available to determine the role of endobronchial ultrasound in pathologic staging . Objectives : To compare the diagnostic yield of endobronchial ultrasound against cervical mediastinoscopy in the diagnosis and staging of radiologically enlarged mediastinal lymph nodes stations accessible by both modalities in patients with suspected nonsmall cell lung cancer . Methods : Prospect i ve , crossover trial with surgical lymph node dissection used as the accepted st and ard . Biopsy results of paratracheal and subcarinal lymph nodes were compared . Results : Sixty-six patients with a mean age 60 ± 10 years were studied . The prevalence of malignancy was 89 % ( 59/66 cases ) . Endobronchial ultrasound had a higher overall diagnostic yield ( 91 % ) compared with mediastinoscopy ( 78 % ; p = 0.007 ) in the per lymph node analysis . There was disagreement in the yield between the two procedures in the subcarinal lymph nodes ( 24 % ; p = 0.011 ) . There were no significant differences in the yield at other lymph node stations . The sensitivity , specificity , and negative predictive value of endobronchial ultrasound were 87 , 100 , and 78 % , respectively . The sensitivity , specificity , and negative predictive value of mediastinoscopy were 68 , 100 , and 59 % , respectively . No significant differences were found between endobronchial ultrasound ( 93 % ) and mediastinoscopy ( 82 % ; p = 0.083 ) in determining true pathologic N stage ( per patient analysis ) . Conclusions : In suspected nonsmall cell lung cancer , endobronchial ultrasound may be preferred in the histologic sampling of paratracheal and subcarinal mediastinal adenopathy because the diagnostic yield can surpass mediastinoscopy OBJECTIVE The study objective was to compare endobronchial ultrasound-guided transbronchial needle aspiration ( EBUS-TBNA ) with mediastinoscopy for mediastinal lymph node staging of potentially resectable non-small cell lung cancer . METHODS Patients with confirmed or suspected non-small cell lung cancer who required mediastinoscopy to determine suitability for lung cancer resection were entered into the trial . All patients underwent EBUS-TBNA followed by mediastinoscopy under general anesthesia . If both were negative for N2 or N3 disease , the patient underwent pulmonary resection and mediastinal lymphadenectomy . RESULTS Between July 2006 and August 2010 , 190 patients were registered in the study , 159 enrolled , and 153 were eligible for analysis . EBUS-TBNA and mediastinoscopy sample d an average of 3 and 4 lymph node stations per patient , respectively . The mean short axis of the lymph node biopsied by EBUS-TBNA was 6.9 ± 2.9 mm . The prevalence of N2/N3 disease was 35 % ( 53/153 ) . There was excellent agreement between EBUS-TBNA and mediastinoscopy for mediastinal staging in 136 patients ( 91 % ; Kappa , 0.8 ; 95 % confidence interval , 0.7 - 0.9 ) . Specificity and positive predictive value for both techniques were 100 % . The sensitivity , negative predictive value , and diagnostic accuracy for mediastinal lymph node staging for EBUS-TBNA and mediastinoscopy were 81 % , 91 % , 93 % , and 79 % , 90 % , 93 % , respectively . No significant differences were found between EBUS-TBNA and mediastinoscopy in determining the true pathologic N stage ( McNemar 's test , P = .78 ) . There were no complications from EBUS-TBNA . Minor complications from mediastinoscopy were observed in 4 patients ( 2.6 % ) . CONCLUSIONS EBUS-TBNA and mediastinoscopy achieve similar results for the mediastinal staging of lung cancer . As performed in this study , EBUS-TBNA can replace mediastinoscopy in patients with potentially resectable non-small cell lung cancer |
12,816 | 15,194,636 | In patients with resectable oesophageal cancer , chemoradiotherapy plus surgery significantly reduces three year mortality compared with surgery alone .
However , postoperative mortality was significantly increased by neoadjuvant chemoradiotherapy . | BACKGROUND The benefit of neoadjuvant chemoradiotherapy in oesophageal cancer has been extensively studied but data on survival are still equivocal .
OBJECTIVE To assess the effectiveness of chemoradiotherapy followed by surgery in the reduction of mortality in patients with resectable oesophageal cancer . | In a prospect i ve multicenter study , 186 patients with squamous cell esophageal carcinoma , who after evaluation were considered suitable for surgery , were r and omized to 4 treatment groups : Group 1 , surgery alone ; Group 2 , pre-operative chemotherapy ( cisplatin and bleomycin ) and surgery ; Group 3 , pre-operative irradiation ( 35 Gy ) and surgery ; Group 4 , pre-operative chemotherapy , radiotherapy , and surgery . Three-year survival was significantly higher in the pooled groups receiving radiotherapy as compared with the pooled groups not receiving radiotherapy . Comparison of the groups having pre-operative chemotherapy with those not having chemotherapy showed no significant difference in survival . Female patients had a significantly better survival than males . The results indicate that pre-operative irradiation had a beneficial effect on intermediate term survival , whereas the chemotherapy regime used did not influence survival . RésuméDans une étude prospect i ve , multicentrique , 186 patients ayant un cancer épidermoïde de l'oesophage ont été r and omisée dans quatre groupes : le groupe 1 a eu la chirurgie seule ; le groupe 2 , une chimiothérapie préopératoire ( cis-platine et bléomycine ) ; le groupe 3 , une radiothérapie préopératoire suivie de chirurgie ; et le groupe 4 , une chimiothérapie et une radiothérapie préopératoires suivies de chirurgie . La survie à trois ans a été supérieure chez l'ensemble des patients ayant reçu la radiothérapie préopératoire par rapport à ceux qui n'en ont pas eu . Aucune différence de survie n'a pu être mise en évidence dans les groupes ayant eu ou pas de chimiothérapie . La survie des femmes a été significativement supérieure à celle des hommes . Ces résultats indiquent que la radiothérapie préopératoire apporte un plus en ce qui concerne la survie à moyen terme , alors que la chimiothérapie n'influence pas la survie . ResumenEn un estudio prospect ivo multicéntrico sobre 186 pacientes con carcinoma escamocelular del esófago c and idatos para cirugía , se constituyeron cuatro grupos para r and omización : Grupo 1 , cirugía solamente ; Grupo 2 , quimioterapia preoperatoria ( cisplatino y bleomicina ) y cirugía ; Grupo 3 , irradiación preoperatoria ( 35 Gy ) y cirugía ; Grupo 4 , quimioterapia preoperatoria , radioterapia y cirugía . La comparación entre el grupo que recibió quimioterapia y el que no la recibió no demostró diferencia significativa en cuanto a supervivencia . Las pacientes femeninas exhibieron una mejor supervivencia que los pacientes masculinos . Los result ados indican que la irradiación preoperatoria tuvo un efecto benéfico sobre la sobrevida a término medio , en tanto que la quimioterapia , en el regimen utilizado , no tuvo influencia sobre la supervivencia Between January 1986 and December 1992 , sixty-nine patients with squamous esophageal cancer were r and omized to one or the other of two treatment groups . Group 1 ( 35 patients ) were scheduled to receive chemotherapy ( cisplatinum and 5-fluorouracil ) and radiation , followed by resection , while group 2 ( 34 patients ) received resection alone . Of the 35 patients entering combined treatment , 26 completed the protocol and 9 received only chemoradiation . A complete response to preoperative therapy was shown by 7 patients , and a partial response by the other 7 patients . Survival rates at one year and five years were slightly better among patients receiving combined treatment than among those undergoing surgery alone , but overall survival did not differ statistically between the two groups . Nor were operative mortality and complications statistical different between the two groups Background . Despite well‐established surgical approaches , the prognosis for patients with squamous cell carcinoma of the esophagus remains dismal . To assess the benefit of adjuvant chemotherapy and radiation therapy ( CRT ) , a r and omized trial with and without sequential preoperative CRT was undertaken ; CRT combined 20 Gy and two courses of 5‐FU and cisplatin OBJECTIVE This study investigated the role of preoperative chemotherapy in squamous cell cancer of the esophagus . METHODS A prospect i ve r and omized trial was undertaken in 147 patients : 74 received preoperative chemotherapy comprising cisplatin and 5-fluorouracil and 73 had surgical therapy alone . End points were cancer and therapy-related deaths . RESULTS Sixty-six patients ( 89 % ) in the chemotherapy group underwent resection compared with 69 ( 95 % ) in the control group ( p = not significant ) . Of the 60 patients who had resection after completing the chemotherapy program , 35 ( 58 % ) had a significant response , of whom four ( 6.7 % ) had a complete pathologic response . Postoperative mortality rates were 8.3 % and 8.7 % in the chemotherapy and control groups , respectively ( p = not significant ) . Significant downstaging was evident with chemotherapy ; curative resections were possible in 67 % of these patients compared with 35 % in the control group ( p = 0.0003 ) . T3 and T4 tumors were found in 67 % and 91 % of the chemotherapy and control groups , respectively ( p = 0.0002 ) . The respective figures for N1 disease were 70 % and 88 % ( p = 0.009 ) . An intent-to-treat analysis of survival showed no significant difference between the two groups . Median survivals were 16.8 and 13 months , respectively ( p = 0.17 ) . Of those who completed the chemotherapy and resection , responders fared better than control patients . Median survivals were 42.2 months and 13.8 months , respectively ( p = 0.003 ) . Median survival ( 8.3 months ) was worse for nonresponders than for control patients ( p = 0.03 ) . The recurrence pattern suggested a significant reduction in locoregional disease with chemotherapy . CONCLUSIONS Preoperative chemotherapy was safe and result ed in significant downstaging and an increased likelihood of curative resection . Survival was not better than that in the surgery-alone group , but responders did fare better than nonresponders BACKGROUND We conducted a multicenter , r and omized trial to compare preoperative chemoradiotherapy followed by surgery with surgery alone in patients with stage I and II squamous-cell cancer of the esophagus . METHODS The preoperative combined therapy consisted of two one-week courses ; each involved radiotherapy , in a dose of 18.5 Gy delivered in five fractions of 3.7 Gy each , and 80 mg of cisplatin per square meter of body-surface area , administered 0 to 2 days before the first day of radiotherapy . The surgical plan included one-stage en bloc esophagectomy and proximal gastrectomy by the abdominal and right thoracic routes , to be performed immediately after r and omization in the group assigned to surgery alone and two to four weeks after the completion of preoperative chemoradiotherapy in the group assigned to combined therapy . RESULTS A total of 297 patients entered the study ; 11 were found to be ineligible , and 4 were lost to follow-up . Of the remaining 282 , 139 were assigned to surgery alone and 143 to combined therapy . After a median follow-up of 55.2 months , no significant difference in overall survival was observed ; the median survival was 18.6 months for both groups . As compared with the group treated with surgery alone , the group treated preoperatively had longer disease-free survival ( P=0.003 ) , a longer interval free of local disease ( P=0.01 ) , a lower rate of cancer-related deaths ( P=0.002 ) , and a higher frequency of curative resection ( P=0.017 ) . However , there were more postoperative deaths ( P=0.012 ) in the group treated preoperatively with chemoradiotherapy . Three prognostic factors were found to influence survival in a multivariate analysis : the disease stage , based on computed tomography ; the location of the tumor ; and whether the surgical resection was curative . CONCLUSIONS In patients with squamous-cell esophageal cancer , preoperative chemoradiotherapy did not improve overall survival , but it did prolong disease-free survival and survival free of local disease BACKGROUND Uncontrolled studies suggest that a combination of chemotherapy and radiotherapy improves the survival of patients with esophageal adenocarcinoma . We conducted a prospect i ve , r and omized trial comparing surgery alone with combined chemotherapy , radiotherapy , and surgery . METHODS Patients assigned to multimodal therapy received two courses of chemotherapy in weeks 1 and 6 ( fluorouracil , 15 mg per kilogram of body weight daily for five days , and cisplatin , 75 mg per square meter of body-surface area on day 7 ) and a course of radiotherapy ( 40 Gy , administered in 15 fractions over a three-week period , beginning concurrently with the first course of chemotherapy ) , followed by surgery . The patients assigned to surgery had no preoperative therapy . RESULTS Of the 58 patients assigned to multimodal therapy and the 55 assigned to surgery , 10 and 1 , respectively , were withdrawn for protocol violations . At the time of surgery , 23 of 55 patients ( 42 percent ) treated with preoperative multimodal therapy who could be evaluated had positive nodes or metastases , as compared with 45 of the 55 patients ( 82 percent ) who underwent surgery alone ( P<0.001 ) . Thirteen of the 52 patients ( 25 percent ) who underwent surgery after multimodal therapy had complete responses as determined pathologically . The median survival of patients assigned to multimodal therapy was 16 months , as compared with 11 months for those assigned to surgery alone ( P=0.01 ) . At one , two , and three years , 52 , 37 , and 32 percent , respectively , of patients assigned to multimodal therapy were alive , as compared with 44 , 26 , and 6 percent of those assigned to surgery , with the survival advantage favoring multimodal therapy reaching significance at three years ( P=0.01 ) . CONCLUSIONS Multimodal treatment is superior to surgery alone for patients with resectable adenocarcinoma of the esophagus BACKGROUND Controversy exists about the best surgical treatment for esophageal carcinoma . METHODS We r and omly assigned 220 patients with adenocarcinoma of the mid-to-distal esophagus or adenocarcinoma of the gastric cardia involving the distal esophagus either to transhiatal esophagectomy or to transthoracic esophagectomy with extended en bloc lymphadenectomy . Principal end points were overall survival and disease-free survival . Early morbidity and mortality , the number of quality -adjusted life-years gained , and cost effectiveness were also determined . RESULTS A total of 106 patients were assigned to undergo transhiatal esophagectomy , and 114 to undergo transthoracic esophagectomy . Demographic characteristics and characteristics of the tumor were similar in the two groups . Perioperative morbidity was higher after transthoracic esophagectomy , but there was no significant difference in in-hospital mortality ( P=0.45 ) . After a median follow-up of 4.7 years , 142 patients had died--74 ( 70 percent ) after transhiatal resection and 68 ( 60 percent ) after transthoracic resection ( P=0.12 ) . Although the difference in survival was not statistically significant , there was a trend toward a survival benefit with the extended approach at five years : disease-free survival was 27 percent in the transhiatal-esophagectomy group , as compared with 39 percent in the transthoracic-esophagectomy group ( 95 percent confidence interval for the difference , -1 to 24 percent [ the negative value indicates better survival with transhiatal resection ] ) , whereas overall survival was 29 percent as compared with 39 percent ( 95 percent confidence interval for the difference , -3 to 23 percent ) . CONCLUSIONS Transhiatal esophagectomy was associated with lower morbidity than transthoracic esophagectomy with extended en bloc lymphadenectomy . Although median overall , disease-free , and quality -adjusted survival did not differ statistically between the groups , there was a trend toward improved long-term survival at five years with the extended transthoracic approach PURPOSE A pilot study of 43 patients with potentially resectable esophageal carcinoma treated with an intensive regimen of preoperative chemoradiation with cisplatin , fluorouracil , and vinblastine before surgery showed a median survival of 29 months in comparison with the 12-month median survival of 100 historical controls treated with surgery alone at the same institution . We design ed a r and omized trial to compare survival for patients treated with this preoperative chemoradiation regimen versus surgery alone . MATERIAL S AND METHODS One hundred patients with esophageal carcinoma were r and omized to receive either surgery alone ( arm I ) or preoperative chemoradiation ( arm II ) with cisplatin 20 mg/m2/d on days 1 through 5 and 17 through 21 , fluorouracil 300 mg/m2/d on days 1 through 21 , and vinblastine 1 mg/m2/d on days 1 through 4 and 17 through 20 . Radiotherapy consisted of 1.5-Gy fractions twice daily , Monday through Friday over 21 days , to a total dose of 45 Gy . Transhiatal esophagectomy with a cervical esophagogastric anastomosis was performed on approximately day 42 . RESULTS At median follow-up of 8.2 years , there is no significant difference in survival between the treatment arms . Median survival is 17.6 months in arm I and 16.9 months in arm II . Survival at 3 years was 16 % in arm I and 30 % in arm II ( P = .15 ) . This study was statistically powered to detect a relatively large increase in median survival from 1 year to 2.2 years , with at least 80 % power . CONCLUSION This r and omized trial of preoperative chemoradiation versus surgery alone for patients with potentially resectable esophageal carcinoma did not demonstrate a statistically significant survival difference BACKGROUND We performed a multi-institutional r and omized trial comparing preoperative chemotherapy followed by surgery with surgery alone for patients with local and operable esophageal cancer . METHODS Preoperative chemotherapy for patients r and omly assigned to the chemotherapy group included three cycles of cisplatin and fluorouracil . Surgery was performed two to four weeks after the completion of the third cycle ; patients also received two additional cycles of chemotherapy after the operation . Patients r and omly assigned to the immediate-surgery group underwent the same surgical procedure . The main end point was overall survival . RESULTS Of the 440 eligible patients with adequate data , 213 were assigned to receive preoperative chemotherapy and 227 to undergo immediate surgery . After a median possible study time of 55.4 months , there were no significant differences between the two groups in median survival : 14.9 months for the patients who received preoperative chemotherapy and 16.1 months for those who underwent immediate surgery ( P=0.53 ) . At one year , the survival rate was 59 percent for those who received chemotherapy and 60 percent for those who had surgery alone ; at two years , survival was 35 percent and 37 percent , respectively . The toxic effects of chemotherapy were tolerable , and the addition of chemotherapy did not appear to increase the morbidity or mortality associated with surgery . There were no differences in survival between patients with squamous-cell carcinoma and those with adenocarcinoma . Weight loss was a significant predictor of poor outcome ( P=0.03 ) . With the addition of chemotherapy , there was no change in the rate of recurrence at locoregional or distant sites . CONCLUSIONS Preoperative chemotherapy with a combination of cisplatin and fluorouracil did not improve overall survival among patients with epidermoid cancer or adenocarcinoma of the esophagus Long-term beta blockade for perhaps a year or so following discharge after an MI is now of proven value , and for many such patients mortality reductions of about 25 % can be achieved . No important differences are clearly apparent among the benefits of different beta blockers , although some are more convenient than others ( or have slightly fewer side effects ) , and it appears that those with appreciable intrinsic sympathomimetic activity may confer less benefit . If monitored , the side effects of long-term therapy are not a major problem , as when they occur they are easily reversible by changing the beta blocker or by discontinuation of treatment . By contrast , although very early IV short-term beta blockade can definitely limit infa rct size , more reliable information about the effects of such treatment on mortality will not be available until a large trial ( ISIS ) reports later this year , with data on some thous and s of patients entered within less than 4 hours of the onset of pain . Our aim has been not only to review the 65-odd r and omized beta blocker trials but also to demonstrate that when many r and omized trials have all applied one general approach to treatment , it is often not appropriate to base inference on individual trial results . Although there will usually be important differences from one trial to another ( in eligibility , treatment , end-point assessment , and so on ) , physicians who wish to decide whether to adopt a particular treatment policy should try to make their decision in the light of an overview of all these related r and omized trials and not just a few particular trial results . Although most trials are too small to be individually reliable , this defect of size may be rectified by an overview of many trials , as long as appropriate statistical methods are used . Fortunately , robust statistical methods exist -- based on direct , unweighted summation of one O-E value from each trial -- that are simple for physicians to use and underst and yet provide full statistical sensitivity . These methods allow combination of information from different trials while avoiding the unjustified direct comparison of patients in one trial with patients in another . ( Moreover , they can be extended of such data that there is no real need for the introduction of any more complex statistical methods that might be more difficult for physicians to trust . ) Their robustness , sensitivity , and avoidance of unnecessary complexity make these particular methods an important tool in trial overviews |
12,817 | 30,366,575 | Results : We found that exercise‐based CR had a significant effect on decreasing anxiety and depression scores .
Furthermore , exercise‐based CR may alleviate anxiety and depressive symptoms at different time periods .
Conclusions : For patients with MI , exercise‐based CR has been demonstrated to alleviate anxiety and depressive symptoms .
These findings highlight CR as essential and beneficial for minimizing MI patient anxiety and depression during recovery | Background : Cardiac rehabilitation ( CR ) has been shown to provide the best social , psychological and physical conditions for patient recovery after myocardial infa rct ion ( MI ) .
Objectives : The aim of present study was to quantify the efficacy of exercise‐based CR treatments in terms of relief from symptoms of anxiety and depression symptoms among patients with MI . | Aim : To examine the effectiveness of a four-week home-based self-management rehabilitation programme on health-related quality of life , anxiety and depression levels , cardiac risks and unplanned visits to the health services among community-dwelling patients with myocardial infa rct ion . Methods : A r and omised controlled trial with repeated measurements was used . A convenience sample of 128 patients with myocardial infa rct ion was recruited from outpatient cardiology clinics at a tertiary hospital in Singapore . Participants were r and omly assigned to the intervention group or control group . The outcomes were measured using Short Form 12-item Health Survey Version 2 , Myocardial Infa rct ion Dimensional Assessment Scale , and Hospital Anxiety and Depression Scale . The cardiac physiological risk parameters and number of unplanned health service use were also assessed . Data were collected at baseline , and at four weeks and 16 weeks from the baseline . Results : Over the 16 weeks , the two groups reported significant differences in physical activity ( F = 4.23 , p = 0.02 ) , dependency ( F = 5.16 , p = 0.01 ) , concerns over medication ( F = 3.47 , p = 0.04 ) on MIDAS , anxiety level ( F = 3.41 , p = 0.04 ) and body mass index ( F = 3.12 , p = 0.04 ) . A significant difference was also found in unplanned cardiac-related emergency room visits ( χ2 = 6.64 , p = 0.036 ) and medical consultation ( χ2 = 9.67 , p = 0.046 ) at the 16-week study point . Conclusion : The study may provide a useful tool to help health care professionals to meet the cardiac rehabilitative care needs of community-dwelling patients with myocardial infa rct ion in Singapore Background Symptoms of depression and anxiety are common after a myocardial infa rct ion ( MI ) . Internet-based cognitive behavioral therapy ( iCBT ) has shown good results in other patient groups . Objective The aim of this study was to evaluate the effectiveness of an iCBT treatment to reduce self-reported symptoms of depression and anxiety among patients with a recent MI . Methods In total , 3928 patients were screened for eligibility in 25 Swedish hospitals . Of these , 239 patients ( 33.5 % , 80/239 women , mean age 60 years ) with a recent MI and symptoms of depression or anxiety were r and omly allocated to a therapist-guided , 14-week iCBT treatment ( n=117 ) , or treatment as usual ( TAU ; n=122 ) . The iCBT treatment was design ed for post-MI patients . The primary outcome was the total score of the Hospital Anxiety and Depression Scale ( HADS ) 14 weeks post baseline , assessed over the internet . Treatment effect was evaluated according to the intention-to-treat principle , with multiple imputations . For the main analysis , a pooled treatment effect was estimated , controlling for age , sex , and baseline HADS . Results There was a reduction in HADS scores over time in the total study sample ( mean delta=−5.1 , P<.001 ) but no difference between the study groups at follow-up ( beta=−0.47 , 95 % CI −1.95 to 1.00 , P=.53 ) . Treatment adherence was low . A total of 46.2 % ( 54/117 ) of the iCBT group did not complete the introductory module . Conclusions iCBT treatment for an MI population did not result in lower levels of symptoms of depression or anxiety compared with TAU . Low treatment adherence might have influenced the result . Trial Registration Clinical Trials.gov NCT01504191 ; https:// clinical trials.gov/ct2/show/NCT01504191 ( Archived at Webcite at http://www.webcitation.org/6xWWSEQ22 There is substantial evidence of the importance of rehabilitation for patients recovering from acute myocardial infa rct ion in reducing mortality , morbidity , and psychological distress . The aim of this study was to compare a recently established home-based coronary rehabilitation programme in a coronary care unit ( CCU ) with the provision of a selection of information leaflets commonly provided for patients after their myocardial infa rct ion . A comparative study was carried out between two r and omly allocated groups of patients receiving either the Heart Manual rehabilitation programme ( n = 17 ) or general advice and information booklets ( n = 17 ) , with follow-up at 1 , 3 and 6 weeks after discharge for both groups . Question naire measurements included anxiety and depression ( HAD score ) , general practitioner ( GP ) visits , and patients ' perception of their confidence of recovery and progress . The findings show that patients receiving the Heart Manual had significantly higher scores in their confidence of recovery and perception of their progress than the group receiving booklets . The Heart Manual group showed improved levels of anxiety with unchanged scores in depression , while patients receiving the booklets experienced increased depression with little change in their anxiety levels . These results help to provide guidance for health care professionals on a form of rehabilitation which is effective for patients and their families in hospital and within the community BACKGROUND A prospect i ve single-center interventional cohort study was conducted to evaluate the effects of a 5-week comprehensive cardiac rehabilitation program on terms exercise capacity , quality of life , echocardiographic findings and autonomic modulation after first-time myocardial infa rct ion . METHODS We studied 37 consecutive post-myocardial infartion patients ( mean age 66 years ) . All patients began a 5-week cardiac rehabilitation supervised training . The exercise program consisted of 40 minutes of training , three times a week , on a cycle ergometer at 60 - 80 % of the maximal heart rate . At baseline and after training program we analyzed : the distance walked after the Six-Minutes Walking Test ( 6MWT ) ; quality of life ( QoL ) assesed using the Psychological General Well-Being Inventory ( PGWBI ) question naire ; echocardiographic finding and autonomic balance assesed heart rate variability ( HRV ) . RESULTS We observed statistically significant improvement in exercise capacity ( from 423±94 to 496±13 m ; P<0.05 ) . Also we observed statistically significant improvements in the many PGWBI dimensions ; particularly , anxiety + 5.8 % ( from 18.11±5.2 to 19.12±4.4 ) ; depression + 6.0 % ( from 12.00±3.0 to 12.73±2.4 ) ; positive well-being + 6 % ( from 11.55±3.5 to 12.23±4.0 ) ; general health + 10.3 % ( from 9.48±3.5 to 10.46±2.87 ) ; vitality + 6.8 % ( from 12.96±4.2 to 13.85±4.2 ) . Finally , we observed changes in HRV indices after training program : RR ( from 903±169 ms to 952±163 ms ; P<0.05 ) , pNN50 % ( from 4.74±4.89 to 6.23±5.53 ; P<0.05 ) , in time-domain ; LF ( from 274±169 to 362±233 ms2 ; P<0,05 ) ; HF ( from 214±154 to 314±194 ms2 ; P<0.05 ) and LF/HF ( from 1.53±0.54 to 1.24±0.47 ; P<0.05 ) in frequency-domain . CONCLUSIONS The study suggest that a cardiac rehabilitation program in postmyocardial infa rct ion improves exercise capacity , QoL and autonomic modulation Background Many patients experience anxiety and depression after cardiac bypass surgery . The aim of this study was to examine the effect of cardiac rehabilitation on anxiety and depression in patients undergoing coronary artery bypass grafting in hospitals affiliated to Shiraz University of Medical Sciences in southern Iran . Methods For this r and omized controlled trial , 80 patients who met the inclusion criteria were recruited and r and omly assigned to case and control groups . Anxiety was measured with the Spielberger Anxiety Scale and depression was measured using Beck ’s Depression Inventory at three points in time : on discharge from the hospital , immediately after the intervention , and 2 months after cardiac rehabilitation . After measuring anxiety and depression in both groups upon discharge , the experimental group participated in 8 cardiac rehabilitation sessions over a 4-week period . The control group received only the routine follow-up care . Results There was a statistically significant difference in depression scores between groups at all three time-points ( Mean score from 19.6 to 10 in the intervention group and from 19.5 to 14 in the control group , P = 0.0014 ) . However , no significant difference was seen in anxiety scores between the groups ( Mean score from 37 to 28 in the intervention group and from 38 to 32 in the control group , P = 0.079 ) . Conclusions Cardiac rehabilitation was effective in reducing depression 2 months after surgery in patients undergoing coronary artery bypass grafting . Trial registration I RCT OBJECTIVES This study evaluated the effectiveness of cardiac counseling and rehabilitation programs led by a nurse counselor , compared with normal care on outcomes for myocardial infa rct ion ( MI ) patients and their partners . METHODS A r and omized controlled trial with follow-up to 1 year was conducted with 100 patients recruited within 72 hours of a first MI and their partners : a Control group received normal care ; an Inpatient group received cardiac rehabilitation from a nurse counselor while in hospital ; and an Extended group received the same cardiac rehabilitation as the Inpatient group , but with additional sessions continuing up to 6 weeks after discharge from hospital . The scales for main outcome measures were 1 ) knowledge of heart disease and treatment ( correct , misconceptions , and uncertainty ) ; 2 ) mood ( Hospital Anxiety and Depression Scale ) ; 3 ) satisfaction ; 4 ) disability ( Functional Limitations Profile ) . RESULTS Inpatient cardiac counseling and rehabilitation result ed in more knowledge , less anxiety , less depression , and greater satisfaction with care in both patients and partners and in less disability in patients , with effects enduring to 1 year . There was some evidence of additional benefit from the Extended program . Both nurse counselors achieved benefits on all outcome variables . CONCLUSIONS This Inpatient cardiac counseling and rehabilitation program result ed in significant and enduring benefits of clinical value . It is likely that it would be acceptable to most post-MI patients , many of whom are not offered or are unable to accept outpatient cardiac rehabilitation Aims The nature of the association of depression and anxiety with risk for acute myocardial infa rct ion ( AMI ) remains unclear . We aim ed to study the prospect i ve association of single and recurrent self-reported symptoms of anxiety and depression with a risk of AMI in a large Norwegian population based cohort . Methods and results In the second wave of the Nord-Trøndelag Health Study ( HUNT2 , 1995–97 ) baseline data on anxiety and depression symptoms , sociodemographic variables , health status including cardiovascular risk factors and common chronic disorders were registered for 57 953 adult men and women free of cardiovascular disease . The cohort was followed up during a mean ( SD ) 11.4 ( 2.9 ) years for a first AMI from baseline through 2008 . A total of 2111 incident AMIs occurred , either identified at hospitals or by the National Cause of Death Registry . The multi-adjusted hazard ratios were 1.31 ( 95 % CI 1.03–1.66 ) for symptoms of depression and 1.25 ( CI 0.99–1.57 ) for anxiety . Two episodes of mixed symptoms of anxiety and depression ( MSAD ) , reported 10 years apart , increased the risk for AMI by 52 % ( 11–108 % ) . After exclusion of the first 5 years of follow-up , the association of depression symptoms with AMI risk was attenuated . Relative risk for AMI with anxiety symptoms and MSAD weakened when participants with chronic disorders were excluded . Conclusion Self-reported symptoms of depression and anxiety , especially if recurrent , were moderately associated with the risk of incident AMI . We had some indications that these associations might partly reflect reverse causation or confounding from common chronic diseases Objective The objective of this secondary analysis was to examine the relationships between a reduction in psychological distress and long-term cardiac and psychological outcomes in post – myocardial infa rct ion patients who participated in a r and omized trial of home-based psychosocial nursing interventions ( the Montreal Heart Attack Readjustment Trial [ M-HART ] ) . Gender differences were considered . Methods We studied 433 patients ( 36.0 % women ) from the M-HART treatment group who received two home visits after achieving a high psychological distress score ( ie , ≥5 ) on the General Health Question naire ( GHQ ) . Short-term GHQ success was determined by a return to a normal GHQ score ( < 5 ) or a reduction of ≥50 % after the two visits . Patients with short-term successful and unsuccessful GHQ outcomes were compared for mid-term maintenance of success , 1-year death and readmission rates , and 1-year depression and anxiety symptoms . Results Patients with short-term GHQ success were more likely to show mid-term GHQ success ( p < .001 ) , marginally less likely to die of any causes ( p = .087 ) , less likely to die of cardiac causes ( p = .043 ) , less likely to be readmitted for any reason ( p < .001 ) and for cardiac reasons ( p < .001 ) , and less likely to have high depression ( p < .001 ) and anxiety ( p < .001 ) at 1-year than patients with short-term unsuccessful GHQ outcomes . Results held for men and women and were not altered by controlling for potential confounders . However , the number of deaths prevented analysis with statistical controls . Conclusions Post – myocardial infa rct ion interventions that reduce psychological distress have the potential to improve long-term prognosis and psychological status for both men and women OBJECTIVES To determine the effectiveness of individualised educational behavioural treatment delivered by cardiac nurses in hospital compared to usual care for patients following acute myocardial infa rct ion . METHODS One hundred and fourteen consecutive patients were r and omised to receive the intervention or usual care . Outcome assessment was by self-report question naire ( the Hospital Anxiety and Depression Scale and Dartmouth COOP Health Status ) , interview at 1 month , and self-report at 3 and 12 months . The primary outcome was improvement in the Dartmouth COOP total score from baseline to 3 months . RESULTS Four patients needed to be treated to give an additional patient with improvement in health status at 3 months ( number needed to treat [ NNT ] 4 , 95 % confidence intervals [ CIs ] 3 to 12 ) . The intervention group were more confident about returning to activities 1 month after discharge from hospital . Treated patients had fewer further treatment needs . CONCLUSIONS An individualised educational behavioural treatment delivered by cardiac nurses in hospital may have substantial benefits . A large-scale pragmatic RCT is needed We have design ed a new 4-week hospitalized phase II cardiac rehabilitation program . The purpose of the present study is to clarify whether the physical and psychological status of patients with myocardial infa rct ion ( MI ) improves after participation in our program . Twenty-nine patients ( 27 males , two females ) with acute MI who enrolled in the 4-week hospitalized phase II rehabilitation program were assessed . All patients enrolled in this study had received coronary interventions . The rehabilitation consisted of exercise training , education and counseling . We evaluated the physical and psychological status of the patients before and just after the program , and at a 6-month follow up . The physical status was assessed by exercise tolerance measured by the peak oxygen consumption and anaerobic threshold , frequency of exercise , and serum concentrations of triglyceride , total cholesterol , high-density lipoprotein-cholesterol , and low-density lipoprotein-cholesterol . The psychological status was assessed by the Spielberger state-trait anxiety inventory question naire ( STAI ) and the self-rating question naire for depression ( SRQ-D ) . Thirty-four patients ( 27 men , seven women ) with MI who did not participate in our rehabilitation program served as a control group . After participation in our rehabilitation program , exercise tolerance and the serum lipid profiles of the patients were improved compared with those before rehabilitation . These parameters had improved significantly 6 months after rehabilitation . The STAI anxiety score was improved significantly and the SRQ-D depression score tended to be improved just after the rehabilitation program . Regular physical activity was continued even 6 months after the completion of the program . Our hospitalized phase II cardiac rehabilitation program improved the management of cardiac risk factors and the psychological status in patients with MI . This comprehensive program may contribute to the secondary prevention of MI as well as the recovery of physical and psychological activities The impact of high levels of psychological stress symptoms in the hospital after an acute myocardial infa rct ion ( AMI ) was examined over 5 years among 461 men who took part in a trial of psychological stress monitoring and intervention . Psychological stress was assessed using the 20-item General Health Question naire ( GHQ ) 1 to 2 days before hospital discharge . Once discharged , patients in the treatment group responded to the GHQ by telephone on a monthly basis and , when they reported high levels of stress symptoms ( GHQ greater than or equal to 5 ) , received visits from nurses to help them deal with their life problems . Control patients received routine medical care after discharge . Post-hoc subgroup analyses based on life-table methods showed that , for patients receiving routine care after discharge , high stress ( GHQ greater than or equal to 5 ) was associated with a close to threefold increase in risk of cardiac mortality over 5 years ( p = 0.0003 ) and an approximately 1.5-fold increase in risk of reinfa rct ion over the same period ( p = 0.09 ) . In contrast , highly stressed patients who took part in the 1-year program of stress monitoring and intervention did not experience any significant long-term increase in risk . Although program impact was significant in terms of reduction of both cardiac mortality ( p = 0.006 ) and AMI recurrences ( p = 0.004 ) among highly stressed patients , there was little evidence of impact among patients with low levels of stress in the hospital . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVES : This study was design ed to assess the prevalence and persistence of symptoms of depression and anxiety during the first 12 months following acute myocardial infa rct ion ( MI ) . DESIGN AND METHODS : In a prospect i ve study , 288 MI patients were assessed for symptoms of depression and anxiety using the Beck Depression Inventory ( BDI ) and the State-Trait Anxiety Inventory ( STAI ) in hospital , 2 - 15 days following MI , and 4 and 12 months subsequently . RESULTS : During hospitalization , 89 ( 30.9 % ) and 75 ( 26.1 % ) patients registered elevated BDI scores ( > /=10 ) and state anxiety scores ( > /=40 ) , respectively . The 4 and 12 month prevalence rates were 37.7 % and 37.2 % for depressive symptoms , and 41.8 % and 40.0 % for anxious symptoms , respectively . Depression and anxiety were highly co-morbid , with 51 % of patients experiencing significant levels of depressive and anxious symptoms at baseline . More than half the patients with complete BDI and state anxiety data experienced either elevated symptoms of anxiety or depression throughout the first year following MI . CONCLUSIONS : Symptoms of depression and anxiety are prevalent , persistent problems during the first year following MI . This study highlights the importance of routine psychological assessment for MI patients both in hospital and after discharge Following an acute myocardial infa rct ion , evaluation of a patient 's own perceptions of health , including mood state , provides useful information about the efficacy of rehabilitation when data are available for patients r and omized to both control and intervention . Data are presented on the Profile of Mood States ( POMS ) in 187 patients , with mild to moderate scores for Spielberger state anxiety and /or Beck depression , who were r and omized within 6 wk of acute myocardial infa rct ion to usual care or to brief cardiac rehabilitation lasting 8 wk and who were followed-up during the 12 months following the acute event . Repeated measures multivariate analysis of covariance identified significant main as well as time effects in POMS scores over 12 months . Repeated measures analysis of variance over the 12 months demonstrated significant improvement for both depression and anxiety in both groups . At 8 wk , improvement was greater in the rehabilitation patients than usual care patients but only in the tension-anxiety , depression-dejection and vigor-activity dimensions of POMS and only in anxiety in those patients with above mean anxiety scores . Overall , rehabilitation and control patients showed similar and significant improvements in anxiety , depression and in mood states over the duration of the 12-month trial Mild to moderate levels of depressive symptoms as characterized by Beck Depression Inventory ( BDI ) scores of > or = 10 are associated with decreased survival after acute myocardial infa rct ion ( AMI ) . We investigated whether lower levels of depressive symptoms are also associated with increased mortality risk after AMI . We prospect ively studied 285 patients with AMI who survived to discharge for evidence , at the time of hospitalization , of a DSM-IIIR mood disorder ( using a structured clinical interview ) and for symptoms of depression ( using the BDI ) . The overall mortality rate at 4 months was 6.7 % . Multiple logistic regression ( chi-square 35.79 , p < or = 0.001 ) revealed that the independent predictors of mortality were : age > or = 65 years , left ventricular ejection fraction < 35 % , diabetes mellitus , and any depression ( DSM-IIIR mood disorder or BDI > or = 10 ) present at the time of AMI . Among patients > or = 65 years old with left ventricular ejection fraction < 35 % , the 4-month mortality was 12 % . However , in this same group , those with any depression at the time of AMI had a 4-month mortality of 50 % ( relative risk 4.1 , p = 0.01 ) . Among patients aged > or = 65 years , the mortality according to BDI scale grouping 0 to 3 , 4 to 9 , and 10 + was 2.6 % , 17.1 % , and 23.3 % , respectively ( p < 0.002 ) . Highest mortality rates were observed in patients with most severe depressive symptoms . However , compared with those without depression , higher mortality was also observed at very low levels of depressive symptoms ( BDI 4 to 9 ) not generally considered clinical ly significant and below the level usually considered predictive of increased post-AMI mortality OBJECTIVE To assess the effects of phase I cardiac rehabilitation intervention on anxiety of patients hospitalized for coronary artery bypass graft ( CABG ) surgery . DESIGN Prospect i ve , quasi-experimental , r and om assignment , repeated measurements . SETTING The Veterans General Hospital Taipei , Taiwan , Republic of China . PATIENTS Seventy patients were r and omly assigned to ( 1 ) the phase I cardiac rehabilitation intervention ( experimental ) group and ( 2 ) the nonintervention ( comparison ) group . Ultimately , 60 subjects were included in the data analyses . OUTCOME MEASURES Psychological status was evaluated by the state of anxiety scores on the State-Trait Anxiety Inventory . Anxiety scores were measured 3 times : ( 1 ) after admission , before the patient underwent CABG surgery ; ( 2 ) the day before the patient underwent CABG surgery ; and ( 3 ) the day of discharge from the hospital . INTERVENTION Individual instruction in progressive exercises and daily activities according to the phase I cardiac rehabilitation program ( Chinese manual ) were used during hospitalization . RESULTS Data analysis was performed with use of generalized estimating equations ( GEE ) to assess the between- and within-group variations . The mean anxiety for all subjects before undergoing CABG surgery was 42.6 . The mean anxiety on the day before undergoing CABG surgery was 33.7 in the experimental group and 49.8 in the comparison group ; there were statistical differences , with a P < .05 level of significance between these 2 groups . The mean anxiety on the day of discharge in the experimental group was 28.6 and in the comparison group was 38.4 ; there were statistical differences , with a P < .05 level of significance between these 2 groups . CONCLUSIONS These results have been supported by similar studies . This finding suggests that application of phase I cardiac rehabilitation intervention can reduce the anxiety level during hospitalization of patients undergoing CABG surgery The psychological impact of exercise training and relaxation therapy was investigated in 156 myocardial infa rct ion patients . They were r and omly assigned to either exercise plus relaxation and breathing therapy ( Treatment A : n = 76 ) or exercise training only ( Treatment B : n = 80 ) . Patients in Treatment A improved on three out of eight psychological measurements ( anxiety , well-being , feelings of invalidity ) . No change was demonstrable in Treatment B. The difference between the treatments was significant for wellbeing ( p less than 0.005 ) . Physical outcome , measured by exercise testing was positive in about half of the patients ( Treatment A : 55 % , Treatment B : 46 % ) . A negative outcome occurred less in Treatment A ( p less than 0.05 ) . Training success was not associated with psychic benefit . The association differed for the two treatments . It was concluded that exercise training was effective for some but not for all cardiac patients , and that a psychic effect of exercise could not be demonstrated . Relaxation therapy enhanced physical and psychic outcome of rehabilitation OBJECTIVE This study evaluated the effects of a home-based rehabilitation program for Chinese patients with myocardial infa rct ion in terms of health-related quality of life and psychological status . METHODS This was a r and omized , controlled trial with data collected at 2 university-affiliated public general hospitals in Xian ( Shaanxi Province , People 's Republic of China ) . One hundred and sixty patients with a myocardial infa rct ion were r and omly assigned to either the interventional group ( a home-based cardiac rehabilitation program using a self-help manual ) or the control group ( usual care ) . Health-related quality of life ( generic , Chinese Short Form 36-Item Health Survey ; disease-specific , Chinese Myocardial Infa rct ion Dimensional Assessment Scale ) and psychological status ( the Chinese Hospital Anxiety and Depression Scale ) were measured at baseline , program completion ( 6 weeks ) , and 3 and 6 months after hospital discharge . RESULTS Significant differences were evident in the main outcomes when the home-based group was compared with the usual care group at 6 weeks , 3 months , and 6 months . The home-based group had significantly higher scores on 4 of the 8 domains of the Chinese Short Form 36-Item Health Survey and on 3 of the 7 dimensions of the Chinese Myocardial Infa rct ion Dimensional Assessment Scale , with significantly lower scores on the anxiety , but not the depression , subscale of the Chinese Hospital Anxiety and Depression Scale . CONCLUSIONS A simple , home-based cardiac rehabilitation program for patients with acute myocardial infa rct ion , using a self-help manual , improves health-related quality of life and reduces anxiety . It appears feasible and acceptable , and does not produce inferior outcomes compared with usualcare in China |
12,818 | 25,467,775 | Perfusion-weighted MRI shows potential in some aspects of diagnosing HNSCC and predicting prognosis . | This systematic review gives an extensive overview of the current state of perfusion-weighted magnetic resonance imaging ( MRI ) for head and neck squamous cell carcinoma ( HNSCC ) . | Prognosis studies are investigations of future events or the evaluation of associations between risk factors and health outcomes in population s of patients ( 1 ) . The results of such studies improve our underst and ing of the clinical course of a disease and assist clinicians in making informed decisions about how best to manage patients . Prognostic research also informs the design of intervention studies by helping define subgroups of patients who may benefit from a new treatment and by providing necessary information about the natural history of a disorder ( 2 ) . There has recently been a rapid increase in the use of systematic review methods to synthesize the evidence on research questions related to prognosis . It is essential that investigators conducting systematic review s thoroughly appraise the method ologic quality of included studies to be confident that a study 's design , conduct , analysis , and interpretation have adequately reduced the opportunity for bias ( 3 , 4 ) . Caution is warranted , however , because inclusion of method ologically weak studies can threaten the internal validity of a systematic review ( 4 ) . This follows abundant empirical evidence that inadequate attention to biases can cause invalid results and inferences ( 5 - 9 ) . However , there is limited consensus on how to appraise the quality of prognosis studies ( 1 ) . A useful framework to assess bias in such studies follows the basic principles of epidemiologic research ( 10 , 11 ) . We focus on 6 areas of potential bias : study participation , study attrition , prognostic factor measurement , confounding measurement and account , outcome measurement , and analysis . The main objectives of our review of review s are to describe methods used to assess the quality of prognosis studies and to describe how well current practice s assess potential biases . Our secondary objective is to develop recommendations to guide future quality appraisal , both within single studies of prognostic factors and within systematic review s of the evidence . We hope this work facilitates future discussion and research on biases in prognosis studies and systematic review s. Methods Literature Search and Study Selection We identified systematic review s of prognosis studies by search ing MEDLINE ( 1966 to October 2005 ) using the search strategy recommended by McKibbon and colleagues ( 12 ) . This strategy combines broad search terms for systematic review s ( systematic review .mp ; meta- analysis .mp ) and a sensitive search strategy for prognosis studies ( cohort , incidence , mortality , follow-up studies , prognos * , predict * , or course ) . We also search ed the reference lists of included review s and method ologic papers to identify other relevant publications . We restricted our search to English- language publications . One review er conducted the search and selected the studies . Systematic review s , defined as review s of published studies with a comprehensive search and systematic selection , were included if they assessed the method ologic quality of the included studies by using 1 or more explicit criteria . We excluded studies if they were meta-analyses of independent patient data only , if their primary goal was to investigate the effectiveness of an intervention or specific diagnostic or screening tests , or if they included studies that were not done on humans . Data Extraction and Synthesis Individual items included in the quality assessment of the systematic review s were recorded as they were reported in the publication ( that is , the information that would be available to readers and future review ers ) . We review ed journal Web sites and contacted the authors of the systematic review s for additional information when authors made such an offer in their original papers . When review s assessed different study design s by using different sets of quality items , we extracted only those items used to assess cohort studies . We constructed a comprehensive list of distinct items that the review s used to assess the quality of their included studies . The full text of each review was screened . All items used by the review authors to assess the quality of studies were extracted into a computerized spreadsheet by 1 review er . Two experienced review ers , a clinical epidemiologist and an epidemiologist , independently synthesized the quality items extracted from the prognosis review s to determine how well the systematic review s assessed potential biases . We did this in 3 steps : 1 ) identified distinct concepts or domains addressed by the quality items ; 2 ) grouped each extracted quality item into the appropriate domain or domains ; and 3 ) identified the domains necessary to assess potential biases in prognosis studies . We then used this information to assess how well the review s ' quality assessment included items from the domains necessary to assess potential biases . After completing each of the first 3 steps , the review ers met to attempt to reach a consensus . The consensus process involved each review er presenting his or her observations and results , followed by discussion and debate . A third review er was available in cases of persistent disagreement or uncertainty . In the first step , all domains addressed by the quality items were identified . The first review er iteratively and progressively defined the domains as items were extracted from the included review s. The second review er defined domains from a r and om list of all extracted quality items . Limited guidance was provided to the review ers so that their assessment s and definitions of domains would be independent . The review ers agreed on a final set of domains that adequately and completely defined all of the extracted items . In the second step , review ers independently grouped each extracted item into the appropriate domains . Review ers considered each extracted item by asking , What is each particular quality item addressing ? or What are the review 's authors getting at with the particular quality assessment item ? . Items were grouped into the domain or domains that best represented the concepts being addressed . For example , the extracted items at least 80 % of the group originally identified was located for follow-up and follow-up was sufficiently complete or does n't jeopardize validity were each independently classified by both review ers as assessing the domain completeness of follow-up adequate , whereas the extracted item quantification and description of all subjects lost to follow-up was classified as assessing the domain completeness of follow-up described . In the third step , we identified the domains necessary to assess potential biases . Each review er considered the ability of the identified domains to adequately address , at least in part , 1 of the following 6 potential biases : 1 ) study participation , 2 ) study attrition , 3 ) prognostic factor measurement , 4 ) confounding measurement and account , 5 ) outcome measurement , and 6 ) analysis . Domains were considered to adequately address part of the framework if information garnered from that domain would inform the assessment of potential bias . For example , both review ers judged that the identified domain study population represents source population or population of interest assessed potential bias in a prognosis study , whereas the domain research question definition did not , although the latter is an important consideration in assessing the inclusion of studies in a systematic review . Finally , on the basis of our previous ratings , we looked at whether each review included items from the domains necessary to assess the 6 potential biases . We calculated the frequency of systematic review s by assessing each potential bias and the number of review s that adequately assessed bias overall . From this systematic synthesis , we developed recommendations for improving quality appraisal in future systematic review s of prognosis studies . We used Microsoft Access and Excel 2002 ( Microsoft Corp. , Redmond , Washington ) for data management and SAS for Windows , version 9.1 ( SAS Institute , Inc. , Cary , North Carolina ) for descriptive statistics . Role of the Funding Sources The funding sources , the Canadian Institutes of Health Research , the Canadian Chiropractic Research Foundation , the Ontario Chiropractic Association , and the Ontario Ministry of Health and Long Term Care , did not have a role in the collection , analysis , or interpretation of the data or in the decision to su bmi t the manuscript for publication . Results We identified 1384 potentially relevant articles . Figure 1 shows a flow chart of studies that were included and excluded . Figure 2 shows the number of review s identified by year of publication . We excluded 131 systematic review s of prognosis studies that did not seem to include any quality assessment of the included studies ; this represented 44 % of prognosis review s. We included 163 review s of prognosis studies in our analysis ( 13 - 175 ) . The most common topics were cancer ( 15 % ) , musculoskeletal disorders and rheumatology ( 13 % ) , cardiovascular ( 10 % ) , neurology ( 10 % ) , and obstetrics ( 10 % ) . Other review s included a wide range of health and health care topics . Sixty-three percent of the review s investigated the association between a specific prognostic factor and a particular outcome ; the remainder investigated multiple prognostic factors or models . The number of primary studies included in each systematic review ranged from 3 to 167 ( median , 18 [ interquartile range , 12 to 31 ] ) . A complete description of the included review s is available from the authors on request . Figure 1 . Flow diagram of inclusion and exclusion criteria of systematic review s. Figure 2 . Number of systematic review s of prognosis studies identified over time . Quality Items One hundred fifty-three review s provided adequate detail to allow extraction of quality items . Eight hundred eighty-two distinct quality items were extracted from the review s. Most review s developed their own set of quality items , with only a few applying criteria from previous review s. Most quality items For the case of pharyngeal carcinomas , the clinical value as well as the stability of several evaluation methods of MR tomographic perfusion measurement are compared . Eighteen patients suffering from histologically proven squamous cell carcinomas were investigated by MR tomography ( 1.5 T , 0.2 mmol/kg Gd‐DTPA ) prior to and during radiation therapy . Perfusion measurements were performed using a double‐echo FLASH sequence . Parameters describing regional blood flow , blood volume , mean transit time , and interstitial concentration of contrast medium ( CM ) were calculated , applying seven different combinations of correction approaches ( separating the shortening of T1 and T2∗ , arterial input function ( AIF ) , and tumor shunts ) . Their correlations to MR independent tumor physiological parameters were analyzed ( metabolic activity measurements using 18F‐FDG‐PET , polarographical pO2 measurement , tumor volume ) . Significant improvements of the correlation between perfusion‐dependent and other tumor physiological parameters could be achieved by decoupling the shortening of T1 and T2∗ and by applying of the tumor shunt model . Deconvolution from the AIF deteriorated the correlation . Therefore , the elimination of the T1 shortening due to interstitial CM proves to be essential for MR perfusion measurements on contrast medium uptaking lesions . Depending on the measurement conditions ( temporal resolution , signal‐to‐noise ratio ) , the consideration of the AIF can even make the results significantly worse by introducing additional measuring errors . PACS numbers : The role of pretreatment dynamic contrast-enhanced perfusion MR imaging ( DCE-PWI ) and diffusion-weighted MR imaging ( DWI ) in predicting the treatment response of oropharyngeal or hypopharyngeal squamous cell carcinoma ( OHSCC ) to chemoradiation remains unclear . We prospect ively investigated the ability of pharmacokinetic parameters derived from pretreatment DCE-PWI and DWI to predict the local control of OHSCC patients treated with chemoradiation . Between August , 2010 and March , 2012 , patients with untreated OHSCC scheduled for chemoradiation were eligible for this prospect i ve study . DCE-PWI and DWI were performed in addition to conventional MRI . The relationship of local control with the following clinical and imaging variables was analyzed : the hemoglobin level , T-stage , tumor location , gross tumor volume , maximum st and ardized uptake value , metabolic tumor volume and total lesion glycolysis on FDG PET/CT , transfer constant ( K trans ) , volume of blood plasma and volume of extracellular extravascular space on DCE-PWI , and apparent diffusion coefficient on DWI of the primary tumor . The patients were also divided into a local control group and a local failure group , and their clinical and imaging parameters were compared . There were 58 patients ( 29 with oropharynx squamous cell carcinoma [ SCC ] and 29 with hypopharynx SCC ) with successful pretreatment DCE-PWI and DWI available for analysis . After a median follow-up of 18.2 months , 17 ( 29.3 % ) participants had local failure , whereas the remaining 41 patients achieved local control . Univariate analysis revealed that only the K trans value was significantly associated with local control ( P = 0.03 ) . When the local control and local failure groups were compared , significant differences were observed in K trans and the tumor location ( P = 0.01 and P = 0.04 , respectively ) . In the multivariable analysis , only K trans was statistically significant ( P = 0.04 ) . Our results suggest that pretreatment K trans may help predict the local control in OHSCC patients treated with chemoradiation PURPOSE To evaluate whether a pharmacokinetic analysis is useful for monitoring the response of oral cancer to chemoradiotherapy ( CRT ) . MATERIAL S AND METHODS Twenty-nine patients were included . They underwent dynamic contrast-enhanced magnetic resonance imaging ( DCE-MRI ) before and after CRT . The DCE-MRI data were analyzed using a Tofts and Kermode ( TK ) model . The histological evaluation of the effects of CRT was performed according to Ohboshi and Shimosato 's classification . RESULTS None of the pre-CRT parameters were significantly different between the responders and nonresponders . The post-CRT volume of the extravascular extracellular space ( EES ) per unit volume of tissue ( v(e ) ) of responders ( 0.397 ± 0.080 ) was higher than that of nonresponders ( 0.281 ± 0.076 ) ( P = 0.01 ) . The change of the v(e ) between the pre- and post-CRT of the responders ( 0.154 ± 0.093 ) was larger than that of the nonresponders ( 0.033 ± 0.073 ) ( P = 0.001 ) . Therefore , the increase in the v(e ) strongly suggested a good tumor response to CRT , which reflected an increase of the EES secondary to the destruction of the cancer nest . The changes in the volume transfer constant ( K(trans ) ) were significantly different between the responders and nonresponders ( P = 0.018 ) . CONCLUSION Both the increase of the v(e ) and the elevation of permeability ( K(trans ) ) were indicative of a good tumor response to CRT . The pharmacokinetic analysis had potential for monitoring the histopathological response to CRT OBJECTIVE MR imaging was prospect ively correlated with pathologic findings to study whether MR imaging can differentiate viable from nonviable tumor tissue in the irradiated carcinoma of the tongue . SUBJECTS AND METHODS MR examinations were performed after radiation therapy in 21 patients with carcinoma of the tongue . All patients underwent either a total glossectomy or hemiglossectomy after radiation therapy . Specimens were examined microscopically . Radiation changes were histologically grade d into four groups ( I , minimal cellular changes ; II , presence of cellular changes and partial destruction of the tumor ; III , only nonviable tumor cells ; IV , no tumor cells ) . MR examinations included T2-weighted imaging , unenhanced T1-weighted imaging , dynamic contrast-enhanced imaging , and contrast-enhanced T1-weighted imaging . RESULTS On unenhanced T1-weighted images , the lesion was hypointense , except for two patients with histologic grade III . On T2-weighted images , the lesion appeared hyperintense in 12 of 14 patients with viable tumor cells ( grade s I and II ) ; however , the lesion was hypointense in four , and isointense in two of seven patients with nonviable tumor cells ( grade s III or IV ) . Contrast-enhanced T1-weighted images showed that the degree of contrast enhancement of the lesion was equal to or lower than that of a normal salivary gl and in 18 of 21 patients . For the time of maximal enhancement of the lesion on dynamic imaging , there was no substantial difference between viable ( grade s I and II ) and nonviable ( grade s III and IV ) tumor tissue . CONCLUSION The present study shows that T2-weighted imaging is feasible for differentiating viable from nonviable tumor tissue in irradiated carcinoma of the tongue PURPOSE Tumor hypoxia adversely affects short term clinical radiation response of head and neck cancer lymph node metastases and long term disease-free survival ( DFS ) in cervix carcinoma . This study was performed to evaluate the relationship between tumor hypoxia and DFS in patients with squamous carcinoma of the head and neck ( SCCHN ) . METHODS AND MATERIAL S Pretreatment tumor pO2 was assessed polarographically in SCCHN patients . All patients were AJCC Stage IV and had pretreatment oxygen measurements taken from locally advanced primaries ( T3 or T4 ) or neck nodes > or = 1.5 cm diameter . Treatment consisted of once daily ( 2 Gy/day to 66 - 70 Gy ) or twice daily irradiation ( 1.25 Gy B.I.D. to 70 - 75 Gy ) + /- planned neck dissection ( for > or = N2A disease ) according to institutional treatment protocol s. RESULTS Twenty-eight patients underwent tumor pO2 measurement . The average pre-treatment median pO2 was 11.2 mm Hg ( range 0.4 - 60 mm Hg ) . The DFS at 12 months was 42 % . The DFS was 78 % for patients with median tumor pO2 > 10 mm Hg but only 22 % for median pO2 < 10 mm Hg ( p = 0.009 ) . The average tumor median pO2 for relapsing patients was 4.1 mm Hg and 17.1 mm Hg in non-relapsing ( NED ) patients ( p = 0.007 ) . CONCLUSION Tumor hypoxia adversely affected the prognosis of patients in this study . Underst and ing of the mechanistic relationship between hypoxia and treatment outcome will allow for the development of new and rational treatment programs in the future PURPOSE The purpose to this study is to identify correlations between pathology and dynamic contrast-enhanced magnetic resonance imaging ( MRI ) and to assess the utility of this technique in the evaluation of radiation response for head and neck cancer . MATERIAL S AND METHODS MRI was prospect ively performed after radiotherapy in 27 patients with various head and neck tumors . After bolus injection of contrast material , a dynamic study was performed using a spoiled gradient-recalled imaging sequence . The maximum slope of increase ( MSI ) on the time-intensity curve was displayed as a color-coded image . The ratio of MSI ( MSIR ) was obtained for tumor and normal muscles . Pathological specimens were obtained after MRI in all cases . Histological grading of irradiation changes was classified into 5 grade s ( 0 - 4 ) . Correlations between MSIR and histological grade were examined . RESULTS Histologically , 18 tumors were classified as grade 2 ( presence of viable tumor cells ) , 4 were grade 3 ( nonviable tumor cells ) , and 5 were grade 4 ( no tumor cells ) . Although the mean + /- SD of MSIR in patients with histological grade 2 or 3 was 7.4 + /- 7.9 , MSIR in patients with grade 4 was 1.8 + /- 0.73 , representing a significant difference ( P < .05 ) . Every patient with grade 4 displayed an MSIR of 2.5 or less , although 5 of 22 patients with grade 2 or 3 had an MSIR of 2.5 or less . CONCLUSIONS MSI quantitatively reflects response to radiotherapy for head and neck cancer . Color-coded MSI display is feasible for depicting permeability changes after radiotherapy BACKGROUND AND PURPOSE : Tumor microenvironment , including blood flow and permeability , may provide crucial information regarding response to chemoradiation therapy . Thus , the objective of this study was to investigate the efficacy of pretreatment DCE-MR imaging for prediction of response to chemoradiation therapy in HNSCC . MATERIAL S AND METHODS : DCE-MR imaging studies were performed on 33 patients with newly diagnosed HNSCC before neoadjuvant chemoradiation therapy by using a 1.5 T ( n = 24 ) or a 3 T ( n = 9 ) magnet . The data were analyzed by using SSM for estimation of Ktrans , ve , and τi . Response to treatment was determined on completion of chemoradiation as CR , with no evidence of disease ( clinical ly or pathologically ) , or PR , with pathologically proved residual tumor . RESULTS : The average pretreatment Ktrans value of the CR group ( 0.64 ± 0.11 minutes−1 , n = 24 ) was significantly higher ( P = .001 ) than that of the PR ( 0.21 ± 0.05 minutes−1 , n = 9 ) group . No significant difference was found in other pharmacokinetic model parameters : ve and τi , between the 2 groups . Although the PR group had larger metastatic nodal volume than the CR group , it was not significantly different ( P = .276 ) . CONCLUSIONS : These results indicate that pretreatment DCE-MR imaging can be potentially used for prediction of response to chemoradiation therapy of HNSCC |
12,819 | 28,151,074 | Conclusion : We did not identify any risk factor interventions with significant effects on MS progression , but the overall QoE was limited . | Background : Several risk factors are associated with multiple sclerosis ( MS ) progression and may be amenable to intervention .
Objective : To systematic ally review the evidence for interventions targeting risk factors for MS progression . | Objective : This study was planned to investigate the efficacy of neuromuscular rehabilitation and Johnstone Pressure Splints in the patients who had ataxic multiple sclerosis . Methods : Twenty-six out patients with multiple sclerosis were the subjects of the study . The control group ( n = 13 ) was given neuromuscular rehabilitation , whereas the study group ( n = 13 ) was treated with Johnstone Pressure Splints in ad dition . Results : In pre- and posttreatment data , significant differences were found in sensation , anterior balance , gait parameters , and Exp and ed Disability Status Scale ( p < 0.05 ) . An important difference was observed in walking-on-two-lines data within the groups ( p < 0.05 ) . There also was a statistically significant difference in pendular movements and dysdiadakokinesia ( p < 0.05 ) . When the posttreatment values were compared , there was no significant difference between sensation , anterior balance , gait parameters , equilibrium and nonequilibrium coordination tests , Exp and ed Disability Status Scale , cortical onset latency , and central conduction time of somatosensory evoked potentials and motor evoked potentials ( p > 0.05 ) . Comparison of values re vealed an important difference in cortical onset-P37 peak amplitude of somatosen sory evoked potentials ( right limbs ) in favor of the study group ( p < 0.05 ) . Conclu sions : According to our study , it was determined that physiotherapy approaches were effective to decrease the ataxia . We conclude that the combination of suitable phys iotherapy techniques is effective multiple sclerosis rehabilitation . Key Words : Multi ple sclerosis — Ataxia — Physical therapy Objective : Low vitamin D status has been associated with multiple sclerosis ( MS ) prevalence and risk , but the therapeutic potential of vitamin D in established MS has not been explored . Our aim was to assess the tolerability of high-dose oral vitamin D and its impact on biochemical , immunologic , and clinical outcomes in patients with MS prospect ively . Methods : An open-label r and omized prospect i ve controlled 52-week trial matched patients with MS for demographic and disease characteristics , with r and omization to treatment or control groups . Treatment patients received escalating vitamin D doses up to 40,000 IU/day over 28 weeks to raise serum 25-hydroxyvitamin D [ 25(OH)D ] rapidly and assess tolerability , followed by 10,000 IU/day ( 12 weeks ) , and further downtitrated to 0 IU/day . Calcium ( 1,200 mg/day ) was given throughout the trial . Primary endpoints were mean change in serum calcium at each vitamin D dose and a comparison of serum calcium between groups . Secondary endpoints included 25(OH)D and other biochemical measures , immunologic biomarkers , relapse events , and Exp and ed Disability Status Scale ( EDSS ) score . Results : Forty-nine patients ( 25 treatment , 24 control ) were enrolled [ mean age 40.5 years , EDSS 1.34 , and 25(OH)D 78 nmol/L ] . All calcium-related measures within and between groups were normal . Despite a mean peak 25(OH)D of 413nmol/L , no significant adverse events occurred . Although there may have been confounding variables in clinical outcomes , treatment group patients appeared to have fewer relapse events and a persistent reduction in T-cell proliferation compared to controls . Conclusions : High-dose vitamin D ( ∼10,000 IU/day ) in multiple sclerosis is safe , with evidence of immunomodulatory effects . Classification of evidence : This trial provides Class II evidence that high-dose vitamin D use for 52 weeks in patients with multiple sclerosis does not significantly increase serum calcium levels when compared to patients not on high-dose supplementation . The trial , however , lacked statistical precision and the design requirements to adequately assess changes in clinical disease measures ( relapses and Exp and ed Disability Status Scale scores ) , providing only Class level IV evidence for these outcomes 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 Background : Preservation of locomotor activity in multiple sclerosis ( MS ) patients is of utmost importance . Robotic-assisted body weight-supported treadmill training is a promising method to improve gait functions in neurologically impaired patients , although its effectiveness in MS patients is still unknown . Objective : To compare the effectiveness of robot-assisted gait training ( RAGT ) with that of conventional walking treatment ( CWT ) on gait and generalized functions in a group of stable MS patients . Methods : A prospect i ve r and omized controlled trial of 12 sessions of RAGT or CWT in MS patients of EDSS score 5–7 . Primary outcome measures were gait parameters and the secondary outcomes were functional and quality of life parameters . All tests were performed at baseline , 3 and 6 months post-treatment by a blinded rater . Results : Fifteen and 17 patients were r and omly allocated to RAGT and CWT , respectively . Both groups were comparable at baseline in all parameters . As compared with baseline , although some gait parameters improved significantly following the treatment at each time point there was no difference between the groups . Both FIM and EDSS scores improved significantly post-treatment with no difference between the groups . At 6 months , most gait and functional parameters had returned to baseline . Conclusions : Robot-assisted gait training is feasible and safe and may be an effective additional therapeutic option in MS patients with severe walking disabilities |
12,820 | 22,608,382 | There is potential promise for video games to improve health outcomes , particularly in the areas of psychological therapy and physical therapy . | CONTEXT Video games represent a multibillion-dollar industry in the U.S. Although video gaming has been associated with many negative health consequences , it also may be useful for therapeutic purpose s. The goal of this study was to determine whether video games may be useful in improving health outcomes . | AIM To evaluate the effects of ' ' Playstation EyeToy Games ' ' on upper extremity motor recovery and upper extremity-related motor functioning of patients with subacute stroke . METHODS The authors design ed a r and omized , controlled , assessor-blinded , 4-week trial , with follow-up at 3 months . A total of 20 hemiparetic in patients ( mean age 61.1 years ) , all within 12 months post-stroke , received 30 minutes of treatment with ' ' Playstation EyeToy Games ' ' per day , consisting of flexion and extension of the paretic shoulder , elbow and wrist as well as abduction of the paretic shoulder or placebo therapy ( watching the games for the same duration without physical involvement into the games ) in addition to conventional program , 5 days a week , 2 - 5 hours/day for 4 weeks . Brunnstrom 's staging and self-care sub-items of the functional independence measure ( FIM ) were performed at 0 month ( baseline ) , 4 weeks ( post-treatment ) , and 3 months ( follow-up ) after the treatment . RESULTS The mean change score ( 95 % confidence interval ) of the FIM self-care score ( 5.5 [ 2.9 - 8.0 ] vs 1.8 [ 0.1 - 3.7 ] , P=0.018 ) showed significantly more improvement in the EyeToy group compared to the control group . No significant differences were found between the groups for the Brunnstrom stages for h and and upper extremity . CONCLUSION ' ' Playstation EyeToy Games ' ' combined with a conventional stroke rehabilitation program have a potential to enhance upper extremity-related motor functioning in subacute stroke patients OBJECTIVE The aim of this study was to assess , using a Web-based format , third-year medical students ' pediatric knowledge and perceptions of game playing with faculty facilitation compared with self- study computerized flash cards . METHODS This study used a repeated- measures experimental design with r and om assignment to a game group or self- study group . Pediatric knowledge was tested using multiple choice exams at baseline , week 6 of the clerkship following a 4-week intervention , and 6 weeks later . Perceptions about game playing and self- study were evaluated using a question naire at week 6 . RESULTS The groups did not differ on content mastery , perceptions about content , or time involved in game playing or self- study . Perceptions about game playing versus self- study as a pedagogical method appeared to favor game playing in underst and ing content ( P<.001 ) , perceived help with learning ( P<.05 ) , and enjoyment of learning ( P<.008 ) . An important difference was increased game group willingness to continue participating in the intervention . CONCLUSIONS Games can be an enjoyable and motivating method for learning pediatric content , enhanced by group interactions , competition , and fun . Computerized , Web-based tools can facilitate access to educational re sources and are feasible to apply as an adjunct to teaching clinical medicine Background Flashbacks are the hallmark symptom of Posttraumatic Stress Disorder ( PTSD ) . Although we have successful treatments for full-blown PTSD , early interventions are lacking . We propose the utility of developing a ‘ cognitive vaccine ’ to prevent PTSD flashback development following exposure to trauma . Our theory is based on two key findings : 1 ) Cognitive science suggests that the brain has selective re sources with limited capacity ; 2 ) The neurobiology of memory suggests a 6-hr window to disrupt memory consolidation . The rationale for a ‘ cognitive vaccine ’ approach is as follows : Trauma flashbacks are sensory-perceptual , visuospatial mental images . Visuospatial cognitive tasks selectively compete for re sources required to generate mental images . Thus , a visuospatial computer game ( e.g. “ Tetris ” ) will interfere with flashbacks . Visuospatial tasks post-trauma , performed within the time window for memory consolidation , will reduce subsequent flashbacks . We predicted that playing “ Tetris ” half an hour after viewing trauma would reduce flashback frequency over 1-week . Methodology /Principal Findings The Trauma Film paradigm was used as a well-established experimental analog for Post-traumatic Stress . All participants viewed a traumatic film consisting of scenes of real injury and death followed by a 30-min structured break . Participants were then r and omly allocated to either a no-task or visuospatial ( “ Tetris ” ) condition which they undertook for 10-min . Flashbacks were monitored for 1-week . Results indicated that compared to the no-task condition , the “ Tetris ” condition produced a significant reduction in flashback frequency over 1-week . Convergent results were found on a clinical measure of PTSD symptomatology at 1-week . Recognition memory between groups did not differ significantly . Conclusions / Significance Playing “ Tetris ” after viewing traumatic material reduces unwanted , involuntary memory flashbacks to that traumatic film , leaving deliberate memory recall of the event intact . Pathological aspects of human memory in the aftermath of trauma may be malleable using non-invasive , cognitive interventions . This has implication s for a novel avenue of preventative treatment development , much-needed as a crisis intervention for the aftermath of traumatic events An interactive multimedia computer game to enhance self-management skills and thereby improve asthma outcomes in inner city children with asthma was evaluated . Subjects aged 6 - 17 were recruited from four pediatric practice s and r and omly assigned to the computer intervention condition or to the usual-care comparison . The main character in the game could match the subject on gender and ethnicity . Characteristics of the protagonist 's asthma were tailored to be like those of the subject . Subjects played the computer game as part of regular asthma visits . Time between pre- and post-test varied from 4 to 15.6 months ( mean , 7.6 months ) . Analysis of covariance , with pre-test scores , age , and asthma severity as covariates , found that the intervention was associated with fewer hospitalizations , better symptom scores , increased functional status , greater knowledge of asthma management , and better child self-management behavior for those in the intervention condition . Interactions with covariates were found and discussed in terms of variable efficacy of the intervention The objective of this study was to test the efficacy and suitability of virtual reality ( VR ) as a pain distraction for pediatric intravenous ( i.v . ) placement . Twenty children ( 12 boys , 8 girls ) requiring i.v . placement for a magnetic resonance imaging/computed tomography ( MRI/CT ) scan were r and omly assigned to two conditions : ( 1 ) VR distraction using Street Luge ( 5DT ) , presented via a head-mounted display , or ( 2 ) st and ard of care ( topical anesthetic ) with no distraction . Children , their parents , and nurses completed self-report question naires that assessed numerous health-related outcomes . Responses from the Faces Pain Scale-Revised indicated a fourfold increase in affective pain within the control condition ; by contrast , no significant differences were detected within the VR condition . Significant associations between multiple measures of anticipatory anxiety , affective pain , i.v . pain intensity , and measures of past procedural pain provided support for the complex interplay of a multimodal assessment of pain perception . There was also a sufficient amount of evidence supporting the efficacy of Street Luge as a pediatric pain distraction tool during i.v . placement : an adequate level of presence , no simulator sickness , and significantly more child- , parent- , and nurse-reported satisfaction with pain management . VR pain distraction was positively endorsed by all reporters and is a promising tool for decreasing pain , and anxiety in children undergoing acute medical interventions . However , further research with larger sample sizes and other routine medical procedures is warranted Blood glucose ( BG ) monitoring ( BGM ) is an important component of diabetes management . New wireless technologies may facilitate BGM and help to optimize glycemic control . We evaluated an integrated wireless approach with and without a motivational game in youth with diabetes . Forty youth , 8 - 18 years old , each received a h and held device fitted with a wireless modem and diabetes data management software , plus a wireless-enabled BG monitor . Half were r and omized to receive the new technologies along with an integrated motivational game in which the participants would guess a BG level following collection of three earlier readings ( Game Group ) . BG data , insulin doses , and carbohydrate intake were displayed graphically prior to the glucose estimation . The other group received the new technologies alone ( Control Group ) . Both groups were instructed to perform BGM four times daily and transmit their data to a central server via the wireless modem . Feasibility of implementation and outcomes were ascertained after 4 weeks . Ninety-three percent of participants successfully transmitted their data wirelessly to the server . The Game Group transmitted significantly more glucose values than the Control Group ( P < 0.001 ) . The Game Group also had significantly less hyperglycemia ( glucose > /=13.9 mmol/L or > /=250 mg/dL ) than the Control Group ( P < 0.001 ) . Youth in the Game Group displayed a significant increase in diabetes knowledge over the 4-week trial ( P < 0.005 ) . Finally , there was a trend for more youth in the Game Group to maintain hemoglobin A1C values < /=8 % ( P = 0.06 ) . Thus a pediatric population with diabetes can successfully implement new technologies to facilitate BGM . Use of a motivational game appears to increase the frequency of monitoring , reduce the frequency of hyperglycemia , and improve diabetes knowledge , and may help to optimize glycemic control The aim of the present study was to determine the user satisfaction of the EyeToy for the training of the upper limb in children with cerebral palsy ( CP ) . User satisfaction was measured in 12 children with CP , using a postexperience question naire , primarily based on a presence question naire . In general , children with CP were satisfied with and motivated by the EyeToy training . In addition , a first evaluation study was performed to determine the effect of this training method on the upper limb function . Ten children with CP were r and omly assigned to the intervention ( mean age 11 years , 9 months ; SD 2,3 ) and the control group ( mean age 12 years , 3 months ; SD 3,2 ) . After a treatment period of 6 weeks , the intervention group completed a user satisfaction question naire . Functional outcome was measured using the Melbourne Assessment scores . Percentage scores of the Melbourne Assessment of 7 of the 10 children were the same or changed only 1 % to 2 % from baseline to followup . However , in the experimental group , two children improved more , 9 % and 13 % respectively . In conclusion , it can be said that the EyeToy is a motivational training tool for the training of children with CP and has the potential to improve upper extremity function BACKGROUND Asthma guidelines urge teaching patients the knowledge and skills required for self-management , based on the assumption that education will lead to improved skills and better asthma control . METHODS In a prospect i ve , r and omized controlled trial of 65 adults with mild-to-moderate asthma , we examined whether an educational self-management intervention would improve adherence to inhaled corticosteroid therapy , decrease markers of airway inflammation , and improve clinical control . Peak flow , symptoms , and adherence were monitored for 7 weeks . After a 1-week run-in , subjects were assigned r and omly to either the educational intervention or control group . The 30-minute intervention was delivered and reinforced at biweekly intervals . RESULTS Compared with the control group , the intervention group had improvements in adherence to inhaled corticosteroid therapy ( by 30 % vs. -5 % , P = 0.01 ) , self-reported control of asthma ( by 14 % vs. 5 % , P = 0.04 ) , and perhaps quality of life ( by 37 % vs. 21 % , P = 0.06 ) . The direction of change for all other clinical outcomes was more favorable in the intervention group , but not significantly so . Markers of inflammation in sputum decreased more in the intervention group , with sputum eosinophils declining significantly ( P = 0.02 ) . CONCLUSION In asthmatic patients treated with inhaled corticosteroids , education and training in self-management improves adherence with inhaled therapy , perceived control of asthma , and sputum eosinophilia OBJECTIVE . Suboptimal adherence to self-administered medications is a common problem . The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other behavioral outcomes for adolescents and young adults with malignancies including acute leukemia , lymphoma , and soft-tissue sarcoma . METHODS . A r and omized trial with baseline and 1- and 3-month assessment s was conducted from 2004 to 2005 at 34 medical centers in the United States , Canada , and Australia . A total of 375 male and female patients who were 13 to 29 years old , had an initial or relapse diagnosis of a malignancy , and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were r and omly assigned to the intervention or control group . The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults . Outcome measures included adherence , self-efficacy , knowledge , control , stress , and quality of life . For patients who were prescribed prophylactic antibiotics , adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices ( n = 200 ) . Adherence to 6-mercaptopurine was assessed through serum metabolite assays ( n = 54 ) . RESULTS . Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group . Self-efficacy and knowledge also increased in the intervention group compared with the control group . The intervention did not affect self-report measures of adherence , stress , control , or quality of life . CONCLUSIONS . The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy . The findings support current efforts to develop effective video-game interventions for education and training in health care Seventy-seven children between the ages of 6 and 10 years , with severe mixed receptive-expressive specific language impairment ( SLI ) , participated in a r and omized controlled trial ( RCT ) of Fast ForWord ( FFW ; Scientific Learning Corporation , 1997 , 2001 ) . FFW is a computer-based intervention for treating SLI using acoustically enhanced speech stimuli . These stimuli are modified to exaggerate their time and intensity properties as part of an adaptive training process . All children who participated in the RCT maintained their regular speech and language therapy and school regime throughout the trial . St and ardized measures of receptive and expressive language were used to assess performance at baseline and to measure outcome from treatment at 9 weeks and 6 months . Children were allocated to 1 of 3 groups . Group A ( n = 23 ) received the FFW intervention as a home-based therapy for 6 weeks . Group B ( n = 27 ) received commercially available computer-based activities design ed to promote language as a control for computer games exposure . Group C ( n = 27 ) received no additional study intervention . Each group made significant gains in language scores , but there was no additional effect for either computer intervention . Thus , the findings from this RCT do not support the efficacy of FFW as an intervention for children with severe mixed receptive-expressive SLI The primary objective of this pilot study was to evaluate the effect of active video games on children 's physical activity levels . Twenty children ( mean ± SD age = 12 ± 1.5 years ; 40 % female ) were r and omised to receive either an active video game up grade package or to a control group ( no intervention ) . Effects on physical activity over the 12-week intervention period were measured using objective ( Actigraph accelerometer ) and subjective ( Physical Activity Question naire for Children [ PAQ-C ] ) measures . An activity log was used to estimate time spent playing active and non-active video games . Children in the intervention group spent less mean time over the total 12-week intervention period playing all video games compared to those in the control group ( 54 versus 98 minutes/day [ difference = -44 minutes/day , 95 % CI [ -92 , 2 ] ] , p = 0.06 ) . Average time spent in all physical activities measured with an accelerometer was higher in the active video game intervention group compared to the control group ( difference at 6 weeks = 194 counts/min , p = 0.04 , and at 12 weeks = 48 counts/min , p = 0.06).This preliminary study suggests that playing active video games on a regular basis may have positive effects on children 's overall physical activity levels . Further research is needed to confirm if playing these games over a longer period of time could also have positive effects on children 's body weight and body mass index . Trial Registration Background The management of burn injuries is reported as painful , distressing and a cause of anxiety in children and their parents . Child 's and parents ' pain and anxiety , often contributes to extended time required for burns management procedures , in particular the process of changing dressings . The traditional method of pharmacologic analgesia is often insufficient to cover the burnt child 's pain , and it can have deleterious side effects [ 1 , 2 ] . Intervention with Virtual Reality ( VR ) games is based on distraction or interruption in the way current thoughts , including pain , are processed by the brain . Research on adults supports the hypothesis that virtual reality has a positive influence on burns pain modulation . Methods This study investigates whether playing a virtual reality game , decreases procedural pain in children aged 5–18 years with acute burn injuries . The paper reports on the findings of a pilot study , a r and omised trial , in which seven children acted as their own controls though a series of 11 trials . Outcomes were pain measured using the self-report Faces Scale and findings of interviews with parent/carer and nurses . Results The average pain scores ( from the Faces Scale ) for pharmacological analgesia only was , 4.1 ( SD 2.9 ) , while VR coupled with pharmacological analgesia , the average pain score was 1.3 ( SD 1.8 ) Conclusion The study provides strong evidence supporting VR based games in providing analgesia with minimal side effects and little impact on the physical hospital environment , as well as its reusability and versatility , suggesting another option in the management of children 's acute pain Implicit self-esteem is the automatic , nonconscious aspect of self-esteem . This study demonstrated that implicit self-esteem can be increased using a computer game that repeatedly pairs self-relevant information with smiling faces . These findings , which are consistent with principles of classical conditioning , establish the associative and interpersonal nature of implicit self-esteem and demonstrate the potential benefit of applying basic learning principles in this domain This article reports the development and evaluation of a computer game ( RightWay Café ) as a special medium to promote a healthy diet for young adults . Structural features of computer games , such as interactive tailoring , role playing , the element of fun , and narrative , were operationalized in the RightWay Café game to afford behavior rehearsal in a safe and entertaining way . Theories such as the health belief model , social cognitive theory , and theory of reasoned action guided the content design of the game to influence mediators of behavior change , including self-efficacy , perceived benefits , perceived barriers , and behavior change intention . A r and omized controlled evaluation study with pretest , posttest , and follow-up design demonstrated that this game was effective in teaching nutrition and weight management knowledge and increasing people 's self-efficacy and perceived benefits of healthy eating , as well as their intention to be on a healthy diet . Limited long-term effects were also found : participants in the game-playing group had greater self-efficacy than participants in the control group after 1 month . This study vali date s the computer game – based approach to health promotion for young adults . Limitations and implication s are also discussed Packy & Marlon , an interactive video game design ed to improve self-care among children and adolescents with diabetes , was evaluated in a six-month r and omized controlled trial . In the game , players take the role of animated characters who manage their diabetes by monitoring blood glucose , taking insulin injections , and choosing foods , while setting out to save a diabetes summer camp from marauding rats and mice who have stolen the diabetes supplies . Study participants were patients aged 8 to 16 from two separate diabetes clinics . Each participant received a Super Nintendo video game system at an initial clinic visit and was r and omly assigned to receive either Packy & Marlon ( treatment group , N = 31 ) or an entertainment video game containing no diabetes-related content ( control group , N = 28 ) . Participants were interviewed and a parent filled out a question naire at baseline , three months , and six months . The findings in this study indicate that well- design ed , educational video games can be effective interventions . There was improvement in the treatment group relative to the control group in terms of diabetes-related self-efficacy ( p = 0.07 ) , communication with parents about diabetes ( p = 0.025 ) , and self-care behaviours ( p = 0.003 ) , and a decrease in unscheduled urgent doctor visits ( p = 0.08 ) . There were no significant differences between the groups in knowledge about diabetes or in glycated haemoglobin ( HbA1c ) levels . Since participants in the study were in general well-controlled patients who were receiving excellent medical care , future research is contemplated involving youngsters who are not under good glycaemic control OBJECTIVE Non-pharmacological approaches to pain management have been used by therapists for decades to reduce the anxiety and pain experienced by children during burn care procedures . With a greater underst and ing of pain and the principles behind what causes a child to be distracted , combined with access to state of the art technology , we have developed an easy to use , h and held multimodal distraction device ( MMD ) . MMD is an interactive device that prepares the child for a procedure and uses developmentally appropriate distraction stories and games during the procedures to alleviate anxiety and pain . This paper summarizes the results of three r and omized control trials . The trials aim ed to underst and the effectiveness of MMD as a distraction and preparation tool in reducing anxiety and pain in children undergoing burns and non-burns medical procedures compared to pure pharmacological approaches St and ard Distraction ( SD ) and off the shelf video games ( VG ) . METHODS Three separate prospect i ve r and omized control trials involving 182 children having 354 dressing changes were conducted in the burns and orthopedic departments at Royal Children 's Hospital , Brisbane , Australia , to address the above aims . Pain and anxiety scores were completed for the child , caregiver and nursing staff according to the Modified Faces , Legs , Activity , Cry and Consolability Scale , Faces Pain Scale-Revised , Visual Analogue Scale and Wong-Baker Faces Pain Rating Scale . Procedural length was recorded . RESULTS MMD as a preparation and distraction tool were shown to have a significant impact on child , parent and nursing staff reported anxiety and pain during procedures compared to st and ard care and video games ( P < 0.01 ) . The MMD had a positive effect on clinical time and was shown to sustain its impact on pain and time with further dressing changes . CONCLUSIONS MMD is more effective in reducing the pain and anxiety experienced by children in acute medical procedures as compared with SD and VG . MMD is continuing to be trialed and is continuing to show positive clinical outcomes PURPOSE Adolescents with chronic illnesses have been shown to have management and treatment issues result ing in poor outcomes . These issues may arise from non-interest in self care and illness knowledge . A video game , " Re-Mission , " was developed to actively involve young people with cancer in their own treatment . Re-Mission provides opportunities to learn about cancer and its treatment . METHOD The efficacy of Re-Mission was investigated in a multi-site , r and omized , controlled study with 375 adolescent and young adult cancer patients . Participants received either a regular commercial game ( control ) or both the regular game plus Re-Mission ( Re-Mission group ) . Participants were given a mini-PC with the games installed and requested to play for an hour each week for 3 months . A test on cancer-related knowledge was given prior to game play ( baseline ) and again after 1 and 3 months . At 3 months the Re-Mission group also rated the acceptability and credibility of Re-Mission . RESULTS Analyses of the knowledge test scores showed that whereas scores of both groups improved significantly over the follow-up periods , the scores of the Re-Mission group improved significantly more . The size of this effect was related to usage of Re-Mission . Credibility scores were negatively correlated with level of knowledge but not with change in knowledge level at 1 month or 3 months . CONCLUSIONS The results indicate a specific effect of Re-Mission play on cancer knowledge that is not attributable to patients ' expectations . It is concluded that video games can be an effective vehicle for health education in adolescents and young adults with chronic illnesses OBJECTIVE To examine how advergames , which are online computer games developed to market a product , affect consumption of healthier and less healthy snacks by low-income African American children . DESIGN Cross-sectional , between-subjects examination of an advergame in which children were rewarded for having their computer character consume healthier or less healthy foods and beverages . Children were r and omly assigned to 1 of the following 3 conditions : ( 1 ) the healthier advergame condition , ( 2 ) the less healthy advergame condition , or ( 3 ) the control condition . SETTING Urban public elementary schools . PARTICIPANTS Thirty low-income , African American children aged 9 to 10 years . Main Exposure Children in the treatment conditions played a less healthy or a healthier version of an advergame 2 times before choosing and eating a snack and completing the experimental measures . Children in the control group chose and ate a snack before playing the game and completing the measures . MAIN OUTCOME MEASURES The number of healthier snack items children selected and ate and how much children liked the game . RESULTS Children who played the healthier version of the advergame selected and ate significantly more healthy snacks than did those who played the less healthy version . Children reported liking the advergame . CONCLUSIONS Findings suggest that concerns about online advergames that market unhealthy foods are justified . However , advergames may also be used to promote healthier foods and beverages . This kind of social marketing approach could tip the scales toward the selection of higher- quality snacks , thereby helping to curb the obesity epidemic The purpose of this study was to evaluate the effectiveness of interactive video games ( combined with stationary cycling ) on health-related physical fitness and exercise adherence in comparison with traditional aerobic training ( stationary cycling alone ) . College-aged males were stratified ( aerobic fitness and body mass ) and then assigned r and omly to experimental ( n = 7 ) or control ( n = 7 ) conditions . Program attendance , health-related physical fitness ( including maximal aerobic power ( VO2 max ) , body composition , muscular strength , muscular power , and flexibility ) , and resting blood pressure were measured before and after training ( 60%-75 % heart rate reserve , 3 d/week for 30 min/d for 6 weeks ) . There was a significant difference in the attendance of the interactive video game and traditional training groups ( 78 % + /- 18 % vs. 48 % + /- 29 % , respectively ) . VO2 max was significantly increased after interactive video game ( 11 % + /- 5 % ) but not traditional ( 3 % + /- 6 % ) training . There was a significantly greater reduction in resting systolic blood pressure after interactive video game ( 132 + /- 6 vs. 123 + /- 6 mmHg ) than traditional ( 131 + /- 7 vs. 128 + /- 8 mmHg ) training . There were no significant changes in body composition after either training program . Attendance mediated the relationships between condition and changes in health outcomes ( including VO2 max , vertical jump , and systolic blood pressure ) . The present investigation indicates that a training program that links interactive video games to cycle exercise results in greater improvements in health-related physical fitness than that seen after traditional cycle exercise training . It appears that greater attendance , and thus a higher volume of physical activity , is the mechanism for the differences in health-related physical fitness Sixty cancer chemotherapy patients were r and omly assigned to one of six conditions formed by a 3(cognitive distraction , relaxation training , no intervention) × 2(high anxiety , low anxiety ) factorial design . All patients were followed for five consecutive chemotherapy sessions . Outcome measures included patient reports , nurse observations , and physiological indices . Results indicated that distraction patients reported less nausea prior to chemotherapy and lower systolic blood pressures after chemotherapy than controls . Relaxation training patients reported less nausea prior to chemotherapy and exhibited lower systolic and diastolic blood pressures after chemotherapy than control patients . There were no significant differences between distraction and relaxation training patients on any measure . Patients with high initial levels of anxiety exhibited continually elevated levels of distress throughout the chemotherapy experience ; however , anxiety level did not interact with the effectiveness of the treatment interventions . Overall , the data support the use of both cognitive distraction and relaxation training for reducing the distress of chemotherapy with both high and low-anxiety patients and suggest that at least some of the effects of relaxation training can be achieved with distraction alone OBJECTIVE The use of computers as a treatment modality in the occupational therapy h and clinic is , as yet , not common practice . A computer interface for wrist movements was developed , and a study to justify the application of such a device is presented . METHOD Forty-seven patients in a day h and clinic who had traumatic fracture of one h and with limitation of wrist mobility participated in the study . Participants were divided into two treatment groups : computer-aided treatment ( high technology ) and traditional brush machine treatment ( low technology ) . A device was developed based on the brush machine in which the brush machine 's mechanism was converted into a medial-lateral joystick . Right-to-left movements were digitally transformed for the use of a computer game . Participants were treated for 5 weeks , and outcome measures included range of motion ( ROM ) , grip strength , edema , and level of interest . RESULTS Results showed significant improvement in ROM , grip strength , and edema across 5 weeks for all participants . Although no significant differences were found between the two groups in ROM , grip strength , and edema , the computer-aided group showed significantly more interest in treatment than did the brush machine group . Finally , the interaction between treatment group and the attitude toward computers was not significant . CONCLUSIONS These results indicate the potential for more interesting motor treatment and rehabilitation of the wrist through the use of computer games . The efficacy of using computers in occupational therapy clinics needs further investigation Unintentional injuries are a leading cause of death and disability for children . Those with developmental disabilities , including children affected by prenatal alcohol exposure , are at highest risk for injuries . Although teaching safety skills is recommended to prevent injury , cognitive limitations and behavioral problems characteristic of children with fetal alcohol spectrum disorder make teaching these skills challenging for parents and teachers . In the current study , 32 children , ages 4 - 10 , diagnosed with fetal alcohol syndrome ( FAS ) and partial FAS , learned fire and street safety through computer games that employed " virtual worlds " to teach recommended safety skills . Children were pretested on verbal knowledge of four safety elements for both fire and street safety conditions and then r and omly assigned to one condition . After playing the game until mastery , children were retested verbally and asked to " generalize " their newly acquired skills in a behavioral context . They were retested after 1 week follow-up . Children showed significantly better knowledge of the game to which they were exposed , immediately and at follow-up , and the majority ( 72 % ) was able to generalize all four steps within a behavioral setting . Results suggested that this is a highly effective method for teaching safety skills to high-risk children who have learning difficulties BACKGROUND Improving asthma knowledge and self-management is a common focus of asthma educational programs , but most programs have had little influence on morbidity outcomes . We developed a novel multiple-component intervention that included the use of an asthma education video game intended to promote adoption of asthma self-management behaviors and appropriate asthma care . OBJECTIVE To determine the effectiveness of an asthma education video game in reducing morbidity among high-risk , school-aged children with asthma . METHODS We enrolled 119 children aged 5 to 12 years from low-income , urban areas in and around San Francisco , CA , and San Jose , CA . Children with moderate-to-severe asthma and parental reports of significant asthma health care utilization were r and omized to participate in the disease management intervention or to receive their usual care ( control group ) . Patients were evaluated for clinical and quality -of-life outcomes at weeks 8 , 32 , and 52 of the study . RESULTS Compared with controls , the intervention group had significant improvements in the physical domain ( P = .04 and P = .01 at 32 and 52 weeks , respectively ) and social activity domain ( P = .02 and P = .05 at 32 and 52 weeks , respectively ) of asthma quality of life on the Child Health Survey for Asthma and child ( P = .02 at 8 weeks ) and parent ( P = .04 and .004 at 32 and 52 weeks , respectively ) asthma self-management knowledge . There were no significant differences between groups on clinical outcome variables . CONCLUSIONS A multicomponent educational , behavioral , and medical intervention targeted at high-risk , inner-city children with asthma can improve asthma knowledge and quality of life BACKGROUND Video game seizures have been reported in photosensitive and non-photosensitive patients with epilepsy . The game Super Mario World , has led to many cases of first seizures . We examined whether this game was indeed more provocative than other programs and whether playing the game added to this effect . METHODS We prospect ively investigated 352 patients in four European cities , using a st and ard protocol including testing of a variety of visual stimuli . We correlated historical data on provocative factors in daily life with electroencephalographic laboratory findings . RESULTS The video game , Super Mario World proved more epileptogenic than st and ard TV programs and as provocative as programs with flashing lights and patterns . Most striking was the fact that video game-viewing and -playing on the 50 and 100 Hz TV was significantly more provocative than viewing the st and ard program ( P < 0.001 , P < 0.05 respectively ) . Playing the video game Mario World on a 50 Hz TV , appeared to be significantly more provocative than playing this game on the 100 Hz TV ( P < 0.001 ) . Of 163 patients with a history of TV- , VG- or CG-seizures , 85 % of them showed epileptiform discharges in response to photic stimulation , 44 % to patterns , 59 % to 50 Hz TV and 29 % to 100 Hz TV . CONCLUSIONS Children and adolescents with a history of video game seizures are , in the vast majority , photosensitive and should be investigated with st and ardised photic stimulation . Games and programs with bright background or flashing images are specifically provocative . Playing a video game on a 100 Hz TV is less provocative [ published with videosequences ] OBJECTIVE We examined the feasibility of Dance Dance Revolution ( DDR ) , a dance video game , in participants ' homes , to increase physical activity ( PA ) and to decrease sedentary screen time ( SST ) . METHODS AND PROCEDURES Sixty children ( 7.5 + /- 0.5 years ) were r and omized in a 2:1 ratio to DDR or to wait-list control ( 10-week delay ) . DDR use was logged , PA was measured objective ly by accelerometry . SST was self-reported at weeks 0 and 10 . At week 28 , after both groups had access to DDR , accelerometry and SST were repeated . RESULTS Mean use of DDR was 89 + /- 82 ( range 0 - 660 min ) min per week ( mpw ) . The DDR group showed increased vigorous PA and a reduction in light PA ; the control group showed no increase in moderate and /or vigorous PA ( MVPA ) although they also had a reduction in light PA . Differences between the groups were not observed . The DDR group also reported a decrease in SST of -1.2 + /- 3.7 h per week ( hpw ) ( P < 0.05 ) , whereas the controls reported an increase of + 3.0 + /- 7.7 hpw ( nonsignificant ) . The difference in SST between the groups was significant , with less SST in the DDR group . Between weeks 10 and 28 , numeric reductions in SST were reported in both groups . In the DDR group , SST at week 28 ( 8.8 + /- 6.0 hpw ) was lower than baseline ( 10.5 + /- 5.5 hpw ; P < 0.03 ) . DISCUSSION This pilot study suggests that DDR reduces SST and may facilitate slight increases in vigorous PA . Further study is needed to better characterize children and context s in which DDR may promote a healthy lifestyle To affect asthma-related knowledge , behavior , and morbidity , research ers tested a new educational intervention for children with asthma : an asthma-specific computer game called Asthma Comm and , which was specifically design ed for this study . Sixty-five children with moderately severe asthma were r and omly assigned to one of two groups , and 54 completed the study . Both groups were seen approximately six times during the 1 year of the study . Control subjects ( n = 29 ) played routine computer games . Experimental subjects ( n = 25 ) played Asthma Comm and . Compared with children in the control group , experimental subjects showed improvement in knowledge about asthma ( P less than .001 ) , behavior related to the management of asthma ( P less than .008 ) , and a trend toward the reduction of acute visits due to asthma ( P less than .13 ) . Children in the experimental group also scored higher on the assessment of behaviors related to the management of asthma that were specifically addressed by the intervention provided by Asthma Comm and ( P less than .01 ) . Differences between the control and experimental groups showed a greater improvement in the experimental group in 21 ( 84 % ) of the 25 outcome variables in the study ( P = .004 , Sign test ) . The study indicates that an asthma-specific computer game can significantly affect knowledge and behavior and may potentially affect morbidity in childhood asthma BACKGROUND AND PURPOSE Performance of laparoscopic surgery requires adequate h and -eye coordination . Video games are an effective way to judge one 's h and -eye coordination , and practicing these games may improve one 's skills . Our goal was to see if there is a correlation between skill in video games and skill in laparoscopy . Also , we hoped to demonstrate that practicing video games can improve one 's laparoscopic skills . SUBJECTS AND METHODS Eleven medical students ( nine male , two female ) volunteered to participate . On day 1 , each student played three commercially available video games ( Top Spin , XSN Sports ; Project Gotham Racing 2 , Bizarre Creations ; and Amped 2 , XSN Sports ) for 30 minutes on an X-box ( Microsoft , Seattle , WA ) and was judged both objective ly and subjectively . Next , the students performed four laparoscopic tasks ( object transfer , tracing a figure-of-eight , suture placement , and knot-tying ) in a swine model and were assessed for time to complete the task , number of errors committed , and h and -eye coordination . The students were then r and omized to control ( group A ) or " training " ( i.e. , video game practicing ; group B ) arms . Two weeks later , all students repeated the laparoscopic skills laboratory and were reassessed . RESULTS Spearman correlation coefficients demonstrated a significant relation between many of the parameters , particularly time to complete each task and h and -eye coordination at the different games . There was a weaker association between video game performance and both laparoscopic errors committed and h and -eye coordination . Group B subjects did not improve significantly over those in group A in any measure ( P > 0.05 for all ) . CONCLUSION Video game aptitude appears to predict the level of laparoscopic skill in the novice surgeon . In this study , practicing video games did not improve one 's laparoscopic skill significantly , but a larger study with more practice time could prove games to be helpful Background Previous studies have shown a correlation between previous video game experience and performance in minimally invasive surgical simulators . The hypothesis is that systematic video game training with high visual-spatial dem and s and visual similarity to endoscopy would show a transfer effect on performance in virtual reality endoscopic surgical simulation . Methods A prospect i ve r and omized study was performed . Thirty surgical novices were matched and r and omized to five weeks of systematic video game training in either a first-person shooter game ( Half Life ) with high visual-spatial dem and s and visual similarities to endoscopy or a video game with mainly cognitive dem and s ( Chessmaster ) . A matched control group ( n = 10 ) performed no video game training during five weeks . Performance in two virtual reality endoscopic surgical simulators ( MIST-VR and GI Mentor II ) was measured pre- and post-training . Before simulator training we also controlled for students ’ visual-spatial ability , visual working memory , age , and previous video game experience . Results The group training with Half Life showed significant improvement in two GI Mentor II variables and the MIST-VR task MD level medium . The group training with Chessmaster only showed an improvement in the MIST-VR task . No effect was observed in the control group . As recently shown in other studies , current and previous video game experience was important for simulator performance . Conclusions Systematic video game training improved surgical performance in advanced virtual reality endoscopic simulators . The transfer effect increased when increasing visual similarity . The performance in intense , visual-spatially challenging video games might be a predictive factor for the outcome in surgical simulation Computer-based education in schools is not novel . However , only a few computer games have been introduced into school-based health education programs . This study describes inclusion of an asthma education space adventure game into fourth- grade classrooms . Using the game improved asthma knowledge in the intervention classes . Children in the active participation classroom gained significantly more asthma knowledge over the observation period compared to the classroom that did not play the computer game . Knowledge gained was retained over a four-week period and the addition of physician-led talks appeared to add little to the knowledge gained . " Air Academy : The Quest for Airtopia " is an easy and successful tool for elementary grade asthma-related health education in schools OBJECTIVE To determine whether an exercise intervention using an active video game ( Dance Dance Revolution [ DDR ] ) is effective in improving endothelial dysfunction ( EDF ) and other risk factors in overweight children . DESIGN Thirty-five children ( Body mass index > or = 85(th ) percentile , mean age 10.21+/-1.67 years , 17 females ) with EDF were assessed for flow-mediated dilation ( FMD ) , lipids , insulin , glucose , NO(2)+NO(3 ) , asymmetric dimethylarginine , symmetric dimethylarginine , l-arginine , height , weight , aerobic fitness , and blood pressure . In a sub sample , tumor necrosis factor alpha , interleukin-6 , C-reactive protein , and adiponectin were also assessed . Subjects were r and omly assigned to 12-weeks of aerobic exercise ( EX ) using DDR or to a non-exercising delayed-treatment control group ( DTC ) . RESULTS EX had significant improvements in FMD ( 5.56+/-5.04 % compared with 0.263+/-4.54 % , p=0.008 ) , exercise time on the grade d exercise test ( 53.59+/-91.54 compared with -12.83+/-68.10 seconds , p=0.025 ) , mean arterial pressure ( MAP ) ( -5.62+/-7.03 compared with -1.44+/-2.16 mmHg , p=0.05 ) , weight ( 0.91+/-1.53 compared with 2.43+/-1.80 kg , p=0.017 ) and peak VO(2 ) ( 2.38+/-3.91 compared with -1.23+/-3.18 mg/kg/min , p=0.005 ) compared with the DTC . Thirteen EX subjects achieved normal EDF while ten did not . These groups differed at baseline with regard to total cholesterol ( TC ) and low-density lipoprotein ( LDL ) . CONCLUSION Twelve weeks of DDR-use improved FMD , aerobic fitness , and MAP in overweight children . Improvements occurred without changes in inflammatory markers or nitric oxide production . The results document the need to explore relationships between obesity , endothelial function , inflammation , lipids , exercise intensity , and gender in a larger sample of overweight children CONTEXT Children 's exposure to violence , blood , sexual themes , profanity , substances , and gambling in the media remains a source of public health concern . However , content in video games played by older children and adolescents has not been quantified or compared with the rating information provided to consumers by the Entertainment Software Rating Board ( ESRB ) . OBJECTIVES To quantify and characterize the content in video games rated T ( for " Teen " ) and to measure the agreement between the content observed in game play and the ESRB-assigned content descriptors displayed on the game box . DESIGN AND SETTING We created a data base of all 396 T-rated video game titles released on the major video game consoles in the United States by April 1 , 2001 , to identify the distribution of games by genre and to characterize the distribution of ESRB-assigned content descriptors . We r and omly sample d 80 video game titles ( which included 81 games because 1 title included 2 separate games ) , played each game for at least 1 hour , quantitatively assessed the content , and compared the content we observed with the content descriptors assigned by the ESRB . MAIN OUTCOME MEASURES Depictions of violence , blood , sexual themes , gambling , and alcohol , tobacco , or other drugs ; whether injuring or killing characters is rewarded or is required to advance in the game ; characterization of gender associated with sexual themes ; and use of profanity in dialogue , lyrics , or gestures . RESULTS Analysis of all content descriptors assigned to the 396 T-rated video game titles showed 373 ( 94 % ) received content descriptors for violence , 102 ( 26 % ) for blood , 60 ( 15 % ) for sexual themes , 57 ( 14 % ) for profanity , 26 ( 7 % ) for comic mischief , 6 ( 2 % ) for substances , and none for gambling . In the r and om sample of 81 games we played , we found that 79 ( 98 % ) involved intentional violence for an average of 36 % of game play , 73 ( 90 % ) rewarded or required the player to injure characters , 56 ( 69 % ) rewarded or required the player to kill , 34 ( 42 % ) depicted blood , 22 ( 27 % ) depicted sexual themes , 22 ( 27 % ) contained profanity , 12 ( 15 % ) depicted substances , and 1 ( 1 % ) involved gambling . Our observations of 81 games match the ESRB content descriptors for violence in 77 games ( 95 % ) , for blood in 22 ( 27 % ) , for sexual themes in 16 ( 20 % ) , for profanity in 14 ( 17 % ) , and for substances in 1 ( 1 % ) . Games were significantly more likely to depict females partially nude or engaged in sexual behaviors than males . Overall , we identified 51 observations of content that could warrant a content descriptor in 39 games ( 48 % ) in which the ESRB had not assigned a content descriptor . We found that the ESRB assigned 7 content descriptors for 7 games ( 9 % ) in which we did not observe the content indicated within 1 hour of game play . CONCLUSIONS Content analysis suggests a significant amount of content in T-rated video games that might surprise adolescent players and their parents given the presence of this content in games without ESRB content descriptors . Physicians and parents should be aware that popular T-rated video games may be a source of exposure to a wide range of unexpected content Although airway disease in preschool children is common , st and ard spirometry is limited by the level of cooperation . We evaluated a computer-animated system ( SpiroGame ) aim ed at improving children 's performance in spirometry . SpiroGame includes a commercial pneumotachograph ( ZAN100 ; ZAN Messgeraete GmbH , Oberthulba , Germany ) and games teaching tidal breathing and all steps of an FVC maneuver . SpiroGame was compared with commercial flow-targeted c and le-blowing software ( MasterLab , Jaeger , Germany ) , and with extrapolated predicted values . Of 112 children aged 3 to 6 yr , 10 refused spirometry and 102 proceeded to FVC games and were r and omized to initially perform either SpiroGame or c and le-blowing . Training lasted 5 to 10 min for SpiroGame and 3 to 7 min for c and le-blowing . Acceptable spirometry was performed by 69 of 102 children with SpiroGame and 48 of 102 with c and le-blowing ( p = 0.005 ) . Order did not affect success . Acceptable FEV(1 ) maneuvers were achieved by 55 children with SpiroGame and two children with c and le-blowing . The intrasubject coefficient of variation was 4.0 % for FVC and 3.3 % for FEV(1 ) with SpiroGame . A premature expiratory break occurred in 41 subjects with c and le-blowing and in six with SpiroGame . FEV(0.5 ) could be measured with both systems . FVC and maximal midexpiratory flow at 50 % of FVC ( MMEF(50 ) ) values were similar , whereas peak expiratory flow was higher with c and le-blowing . In 39 healthy children , most parameters with SpiroGame were similar to extrapolated normal values . We conclude that an interactive computer-animated system facilitates successful spirometry in preschool children STUDY DESIGN R and omized controlled trial . OBJECTIVES To compare the effects of wobble board exercises with and without feedback provided through integrating the wobble board movement into a computer game system , by comparing changes in postural stability and motivation . BACKGROUND Therapeutic exergaming systems may offer a solution to poor adherence to postural control exercise regimes by improving motivation levels during exercise performance . METHODS Twenty-two healthy adults , r and omly assigned to an exergaming group ( n = 11 ) and a control group ( n = 11 ) , completed 12 exercise sessions . Dynamic postural stability was quantified at baseline and follow-up using the star excursion balance test and the dynamic postural stability index during a jump-l and ing task . Intrinsic motivation was measured at baseline using the Self-Motivation Inventory and at follow-up using the Intrinsic Motivation Inventory . RESULTS Star excursion balance test scores showed a statistically significant ( P<.008 ) improvement in the posteromedial and posterolateral direction for both groups . No within-group change for the dynamic postural stability index or between-group difference for star excursion balance test or dynamic postural stability index scores were observed . The " interest and enjoyment " category of the Intrinsic Motivation Inventory showed significantly higher scores ( P<.001 ) in the exergaming group at follow-up , which was 1 of the 5 Intrinsic Motivation Inventory categories evaluated . CONCLUSIONS The findings suggest that exercising with the therapeutic exergaming system showed similar improvements in dynamic postural stability and showed a greater level of interest and enjoyment when compared to a group doing similar balance training without the game system . LEVEL OF EVIDENCE Therapy , level 2b INTRODUCTION The purpose of this r and omized control trial was to evaluate the effects of a computer-assisted instructional ( CAI ) game on asthma symptoms ( eg , coughing , wheezing , shortness of breath , and nighttime awakenings ) in 7- to 12-year-old inner-city children over 12 weeks . METHOD A CAI that focused on reducing environmental irritants/allergens and the correct use of prescribed medications to prevent asthma symptoms was used with 101 children ( 56 in the intervention group and 45 in the control group ) . The primary outcome evaluated a change in children 's asthma symptoms as measured by responses to nine symptom questions in Juniper 's Pediatric Asthma Quality of Life Question naire ( PAQOL ) and measurements of lung function . RESULTS No significant changes in asthma symptoms occurred between the two groups before and after the intervention . No significant changes were noted in PAQOL scores for activities , emotions , and total PAQOL score , lung function measurements , and asthma severity between the two groups . Asthma knowledge of both groups was high before intervention , but there were no significant changes between groups after the intervention . DISCUSSION Findings indicate that this CAI game was not effective in improving asthma symptoms in this group of children BACKGROUND Video games have received widespread application in health care for distraction and behavior modification therapy . Studies on the effect of cognitive distraction during the preoperative period are lacking . We evaluated the efficacy of an interactive distraction , a h and -held video game ( VG ) in reducing preoperative anxiety in children . METHODS In a r and omized , prospect i ve study of 112 children aged 4 - 12 years undergoing outpatient surgery , anxiety was assessed after admission and again at mask induction of anesthesia , using the modified Yale Preoperative Anxiety Scale ( mYPAS ) . Postoperative behavior changes were assessed with the Posthospital Behavior Question naire ( PHBQ ) . Patients were r and omly assigned to three groups : parent presence ( PP ) , PP+a h and -held VG , and PP+0.5 mg.kg-1 oral midazolam ( M ) given>20 min prior to entering the operating room . RESULTS There was a statistically significant increase in anxiety ( P<0.01 ) in groups M and PP at induction of anesthesia compared with baseline , but not in VG group . VG patients demonstrated a decrease in anxiety from baseline ( median change in mYPAS -3 ) , the difference compared with PP ( + 11.8 ) was significant ( P=0.04 ) . The change in anxiety in the M group ( + 7.3 ) was not statistically different from other groups . Sixty-three percent of patients in VG group had no change or decrease in anxiety after treatment , compared with 26 % in M group and 28 % in PP group ( P=0.01 ) . There was no difference in anxiety changes between female and male patients . CONCLUSIONS A h and -held VG can be offered to most children as a low cost , easy to implement , portable , and effective method to reduce anxiety in the preoperative area and during induction of anesthesia . Distraction in a pleasurable and familiar activity provides anxiety relief , probably through cognitive and motor absorption The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating experience . To encourage dissemination of the CONSORT 2010 Statement , this article is freely accessible on bmj.com and will also be published in the Lancet , Obstetrics and Gynecology , PLoS Medicine , Annals of Internal Medicine , Open Medicine , Journal of Clinical Epidemiology , BMC Medicine , and Trials |
12,821 | 15,069,009 | The Task Force found insufficient evidence to recommend for or against using these tests to screen middle-aged and older men and women .
They recommended against screening children , adolescents , or young adults .
No effect was seen among men with a normal baseline result on exercise tolerance testing .
It is not clear from the report of this post hoc analysis whether the cardiovascular risk profiles of participants with an abnormal result on exercise tolerance testing at baseline differed significantly from those of participants with a normal result . | Coronary heart disease is the leading cause of death in the United States .
Each year , more than 1 million Americans experience nonfatal or fatal myocardial infa rct ion or sudden death from coronary heart disease .
Coronary heart disease can also present as angina , but only 20 % of acute coronary events are preceded by long-st and ing angina ( 1 ) .
An estimated 1 to 2 million middle-aged men have asymptomatic but physiologically significant coronary artery obstruction , which puts them at increased risk for coronary heart disease events ( 2 , 3 ) .
The economic burden of coronary heart disease is also substantial .
The direct and indirect costs of coronary heart disease in the United States are projected to total $ 129.9 billion for 2003 ( 1 ) .
The clinical and economic impact of coronary heart disease is the basis for considerable public health interest in the development of effective strategies to reduce the incidence of coronary heart disease events .
In 1996 , the U.S. Preventive Services Task Force considered the use of resting electrocardiography or exercise tolerance testing to detect asymptomatic coronary artery disease and prevent coronary heart disease events ( 4 ) .
The second strategy involves supplementation of screening based on traditional risk factors with additional tests to provide further information about future risk for coronary heart disease or to detect severe blockages of the coronary arteries that might warrant treatment .
Detection of increased risk for future coronary heart disease events may lead to intensified use of risk-reducing treatments .
Some risk-reducing treatments are directed at traditional risk factors ( for example , therapy with statins for hyperlipidemia ) , whereas others are not ( for example , aspirin therapy ) .
Whether revascularization will reduce the risk for coronary heart disease events in persons identified by screening is unknown .
Exercise tolerance testing is widely used as a diagnostic test in the initial evaluation of patients with symptoms suggestive of myocardial ischemia and in persons with previously recognized coronary heart disease .
Although exercise tolerance testing has been applied and studied as a screening or prognostic test in asymptomatic persons , its utility in this group is controversial .
Because direct evidence on possible benefits of screening exercise tolerance testing is lacking , we used data from observational cohort studies to examine whether screening exercise tolerance testing could detect clinical ly significant asymptomatic obstructions of the coronary arteries or provide greater independent prognostic information about the risk for future coronary heart disease events than would be obtained solely by st and ard history , physical examination , and measurement of traditional risk factors .
We also sought information about harms of screening , including the likelihood of false-positive results and the effect of labeling a person as being at high risk . | 1 . Frei B , Engl and L , Ames BN . Ascorbate is an outst and ing antioxidant in human blood plasma . Proc Natl Acad Sci U S A 1989;86:6377–6381 . 2 . Ting HH , Timimi FK , Boles KS , Creager SJ , Ganz P , Creager MA . Vitamin C improves endothelium-dependent vasodilation in patients with non-insulindependent diabetes mellitus . J Clin Invest 1996;97:22–28 . 3 . Heitzer T , Just H , Munzel T. Antioxidant vitamin C improves endothelial dysfunction in chronic smokers . Circulation 1996;94:6–9 . 4 . Slakey D , Roza A , Pieper G , Johnson C , Adams M. Delayed cardiac allograft rejection due to combined cyclosporine and antioxidant therapy . Transplantation 1993;56:1305–1309 . 5 . Fish RD , Nabel EG , Selwyn AP , Ludmer PL , Mudge GH , Kirshenbaum JM , Schoen FJ , Alex and er RW , Ganz P. Responses of coronary arteries of cardiac transplant patients to acetylcholine . J Clin Invest 1988;81:21–31 . 6 . Davis SF , Yeung AC , Meredith IT , Charbonneau F , Ganz P , Selwyn AP , And erson TJ . Early endothelial dysfunction predicts the development of transplant coronary artery disease at 1 year posttransplant . Circulation 1996;93:457– 462 . 7 . Morrow JD , Roberts LJ II . Mass spectrometric quantification of F2-isoprostanes in biological fluids and tissues as measure of oxidant stress . Methods Enzymol 1999;300:3–12 . 8 . Watanabe H , Kakihana M , Ohtsuka S , Sugishita Y. R and omized , double-blind , placebo-controlled study of ascorbate on the preventive effect of nitrate tolerance in patients with congestive heart failure . Circulation 1998;97:886–891 CONTEXT Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease ( CVD ) risk factors , but the role of physical inactivity is not prominent in these recommendations . OBJECTIVE To quantify the influence of low cardiorespiratory fitness , an objective marker of physical inactivity , on CVD and all-cause mortality in normal-weight , overweight , and obese men and compare low fitness with other mortality predictors . DESIGN Prospect i ve observational data from the Aerobics Center Longitudinal Study . SETTING Preventive medicine clinic in Dallas , Tex . PARTICIPANTS A total of 25714 adult men ( average age , 43.8 years [ SD , 10.1 years ] ) who received a medical examination during 1970 to 1993 , with mortality follow-up to December 31 , 1994 . MAIN OUTCOME MEASURES Cardiovascular disease and all-cause mortality based on mortality predictors ( baseline CVD , type 2 diabetes mellitus , high serum cholesterol level , hypertension , current cigarette smoking , and low cardiorespiratory fitness ) stratified by body mass index . RESULTS During the study period , there were 1025 deaths ( 439 due to CVD ) during 258781 man-years of follow-up . Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors . Using normal-weight men without CVD as the referent , the strongest predictor of CVD death in obese men was baseline CVD ( age- and examination year-adjusted relative risk [ RR ] , 14.0 ; 95 % confidence interval [ CI ] , 9.4 - 20.8 ) ; RRs for obese men with diabetes mellitus , high cholesterol , hypertension , smoking , and low fitness were similar and ranged from 4.4 ( 95 % CI , 2.7 - 7.1 ) for smoking to 5.0 ( 95 % CI , 3.6 - 7.0 ) for low fitness . Relative risks for all-cause mortality in obese men ranged from 2.3 ( 95 % CI , 1.7 - 2.9 ) for men with hypertension to 4.7 ( 95 % CI , 3.6 - 6.1 ) for those with CVD at baseline . Relative risk for all-cause mortality in obese men with low fitness was 3.1 ( 95 % CI , 2.5 - 3.8 ) and in obese men with diabetes mellitus 3.1 ( 95 % CI , 2.3 - 4.2 ) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels . Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors . Approximately 50 % ( n = 1674 ) of obese men had low fitness , which led to a population -attributable risk of 39 % for CVD mortality and 44 % for all-cause mortality . Baseline CVD had population attributable risks of 51 % and 27 % for CVD and all-cause mortality , respectively . CONCLUSIONS In this analysis , low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors BACKGROUND The objective of this study was to examine the association of Joint National Committee ( JNC-V ) blood pressure and National Cholesterol Education Program ( NCEP ) cholesterol categories with coronary heart disease ( CHD ) risk , to incorporate them into coronary prediction algorithms , and to compare the discrimination properties of this approach with other noncategorical prediction functions . METHODS AND RESULTS This work was design ed as a prospect i ve , single-center study in the setting of a community-based cohort . The patients were 2489 men and 2856 women 30 to 74 years old at baseline with 12 years of follow-up . During the 12 years of follow-up , a total of 383 men and 227 women developed CHD , which was significantly associated with categories of blood pressure , total cholesterol , LDL cholesterol , and HDL cholesterol ( all P<.001 ) . Sex-specific prediction equations were formulated to predict CHD risk according to age , diabetes , smoking , JNC-V blood pressure categories , and NCEP total cholesterol and LDL cholesterol categories . The accuracy of this categorical approach was found to be comparable to CHD prediction when the continuous variables themselves were used . After adjustment for other factors , approximately 28 % of CHD events in men and 29 % in women were attributable to blood pressure levels that exceeded high normal ( > or = 130/85 ) . The corresponding multivariable-adjusted attributable risk percent associated with elevated total cholesterol ( > or = 200 mg/dL ) was 27 % in men and 34 % in women . CONCLUSIONS Recommended guidelines of blood pressure , total cholesterol , and LDL cholesterol effectively predict CHD risk in a middle-aged white population sample . A simple coronary disease prediction algorithm was developed using categorical variables , which allows physicians to predict multivariate CHD risk in patients without overt CHD Data concerning the natural history of asymptomatic coronary artery disease ( CAD ) has been limited to epidemiologic rather than angiographic studies , thus leading to uncertainty as to whether warning symptoms and signs will identify subjects with silent myocardial ischemia before morbid events . To address this issue , 50 apparently healthy men with angiographically proven CAD and asymptomatic exercise-induced ST depression have been followed prospect ively for 15 years in the Oslo Ischemia Study . Fourteen men died . The initial presenting clinical event in these 14 men was chest pain in 4 (30%)--but in only 1 case was it recognized as typical angina -- silent myocardial infa rct ion in 5 ( 35 % ) and sudden death in 5 ( 35 % ) . Thirty-six men survived , with 19 developing symptoms . Overall , chest pain was the first clinical event in 22 of the total of 33 men with symptoms ( 66 % ) , whereas myocardial infa rct ion occurred in 6 ( 18 % ) and sudden death in 5 ( 16 % ) . Although chest pain occurred in 22 men , it was clinical ly diagnosed as typical angina pectoris in only 6 . These observations suggest that there is an absence of clear-cut ischemic symptoms in many asymptomatic patients before morbid events There is universal agreement [ 1 - 4 ] that women 50 to 69 years of age should undergo screening mammography because r and omized , controlled trials have shown that such screening reduces breast cancer mortality in this age group [ 5 , 6 ] . This consensus is bolstered by the results of cost-effectiveness analyses that consistently show that this benefit can be achieved at a reasonable cost [ 7 - 9 ] . In contrast , whether women 40 to 49 years of age should undergo screening mammography is controversial [ 10 - 15 ] . Pooled results of large r and omized , controlled trials have shown no mortality reduction in 40- to 49-year-old women after 7 to 9 years of screening [ 5 , 16 - 18 ] . However , a statistically significant reduction in breast cancer mortality becomes apparent 10 to 14 years after the initiation of screening [ 19 ] . Some authors have argued that this delayed benefit should not be ignored [ 11 ] . However , the reality of constrained health care re sources requires that any benefit from preventive services be achieved at a reasonable cost . Two recently published analyses [ 20 , 21 ] suggest that mammographic screening in younger women may be as cost-effective as screening in older women . The first analysis [ 20 ] calculated average cost-effectiveness by comparing a strategy of screening 40- to 69-year-old women with no screening . Most of the benefit achieved by using this strategy occurs when women are 50 to 69 years of age . Therefore , this analysis did not address whether it is cost-effective to screen women from 40 to 49 years of age in addition to screening them from 50 to 69 years of age . To determine whether the additional benefit obtained by extending screening mammography to women 40 to 49 years of age comes at a reasonable cost would require an incremental cost-effectiveness analysis [ 22 - 26 ] . The second analysis [ 21 ] used a simplified life-expectancy accounting method , did not discount costs or benefits , and associated screening mammography with unsubstantiated mortality reductions ( 30 % for the base case ) . Neither analysis [ 20 , 21 ] included an important aspect of the results of screening mammography trials in 40- to 49-year-old women : that is , no benefit occurs until 10 years after the initiation of screening . An earlier analysis [ 10 ] found screening mammography to be more expensive in women 40 to 49 years of age than in women 50 years of age and older . This previous analysis calculated incremental cost-effectiveness , discounted costs and benefits , and included an estimated delay between the onset of screening and the onset of a mortality benefit . Our analysis extends this work by including up date d pooled results of the r and omized , controlled trials [ 19 ] ; actual delay times before the onset of benefits ; and up date d costs of mammography and treatment of breast cancer . Methods Model We developed a Markov model [ 27 , 28 ] that compared the life expectancy of women undergoing different breast cancer screening strategies . Except for women in whom breast cancer was diagnosed at the initiation of screening , women were healthy at entry into the model . At the end of each 1-year cycle , women were in one of four health states : They remained healthy , developed breast cancer and remained alive , died of breast cancer , or died of another cause . The transition probabilities [ that is , the probabilities of developing breast cancer , dying of breast cancer , and dying of another cause ] were both age- and strategy -dependent . The base-case analysis compared three strategies : 1 ) no screening ; 2 ) screening biennially from 50 to 69 years of age ; and 3 ) screening every 18 months from 40 to 49 years of age , followed by screening biennially from 50 to 69 years of age . The rationale for these screening intervals is discussed below . We calculated the cost-effectiveness of screening in women 50 years of age and older by comparing the first strategy with the second strategy . To determine the incremental cost-effectiveness of screening in 40- to 49-year-old women , we compared the second and third strategies . Costs and benefits were discounted at a rate of 3 % per year for the base-case analysis [ 23 ] . Benefits Trials of screening mammography have shown no reduction in breast cancer mortality among screened women until several years after the initiation of screening [ 5 , 18 , 29 , 30 ] . Meta-analyses and one pooled analysis have shown that among 40- to 49-year-old women , the summary relative risk reduction in breast cancer mortality 7 to 9 years after the initiation of screening is about 1 , indicating no reduction in mortality [ 5 , 16 - 18 ] . Ten to 12 years after the initiation of screening , a nonsignificant trend toward reduced mortality is evident in the screened group ( Figure 1 , left ) [ 5 , 18 , 29 , 30 ] . Recently up date d results show a statistically significant 16 % reduction that occurs 10 to 14 years after the initiation of screening [ 19 ] . For women 50 to 69 years of age , there is an initial period of about 5 years that shows no benefit from screening ( Figure 1 , right ) [ 18 , 29 , 30 ] . Figure 1 . Cumulative breast cancer mortality in screened ( black circles ) compared with nonscreened ( white circles ) women . Left . Right . In our model , for women who start screening at 50 years of age , a 27 % reduction in breast cancer mortality ( Table 1 ) [ 5 ] begins 5 years after the initiation of screening and continues until age 74 years . Although screening ends at 69 years of age , we assumed that women would continue to benefit for another 5 years because of early detection of breast cancer in the last years of screening . For women who begin screening at 40 years of age , a 16 % reduction in breast cancer mortality starts at age 50 years ; this reduction increases to 27 % at age 55 years . Table 1 . Information Used To Calculate Life Expectancy Screening Interval The screening interval in r and omized , controlled trials of screening mammography has varied from 12 to 33 months for women 50 years of age and older . Pooled results of the efficacy of mammography stratified by length of screening interval do not differ for women in this age group [ 5 ] . From published results [ 5 ] , we determined a 28 % ( 95 % CI , 15 % to 31 % ) reduction in breast cancer mortality in women 50 years of age and older who were screened every 18 to 33 months and a 25 % ( CI , 1 % to 43 % ) reduction in those screened every 12 months . For the base-case analysis , we therefore chose to perform biennial screening in women 50 years of age and older because screening more often only increases cost without increasing the benefits of screening . For the base-case analysis , we used the pooled reduction in breast cancer mortality ( 27 % ) [ 5 ] from all r and omized , controlled trials to determine the cost-effectiveness of biennial screening in 50- to 69-year-old women ; in a sensitivity analysis , we determined the cost-effectiveness of annual screening . The screening interval in r and omized , controlled trials has varied from 12 to 24 months for women 40 to 49 years of age . Pooled results of the efficacy of screening mammography stratified by length of screening interval did not show a statistically significant reduction in breast cancer mortality for 12-month or 18- to 24-month screening intervals [ 5 ] . As noted above , recently reported pooled results of all r and omized , controlled trials , which on average used a screening interval of 18 months , showed a statistically significant 16 % reduction in breast cancer mortality 10 to 14 years after the initiation of screening [ 19 ] . We therefore assumed that a 16 % reduction in breast cancer mortality would be achieved with screening done every 18 months . This screening interval is consistent with the guidelines of organizations [ 2 , 3 ] that recommend screening every 1 to 2 years for 40- to 49-year-old women . In sensitivity analyses , we calculated the cost-effectiveness of annual and biennial screening , assuming the same 16 % reduction in breast cancer mortality among screened women . Utilities Because there are few data on the utility that women place on life after treatment of breast cancer or the utility placed on living with metastatic breast cancer , we did not include utilities in the base-case analysis . Data from a small Australian study [ 33 ] ( which observed a utility of about 0.8 for life after treatment of breast cancer and a utility of about 0.3 for life with metastatic cancer ) are included in a sensitivity analysis to determine the extent to which cost per year of life saved might differ from cost per quality -adjusted life-year saved . Costs We included three costs : the cost of screening mammographic examinations , the cost of evaluating abnormal mammograms , and the cost of treating breast cancer ( Table 2 ) . Additional details on derivations of costs are given in the Appendix . The cost of screening mammography was based on the average cost ( $ 91 ) reported by the National Cancer Institute 's National Survey of Mammography Facilities [ 34 ] . This cost was inflated to 1995 dollars ( $ 106 ) by using the consumer price index for medical services . We assumed that women in whom breast cancer was diagnosed continued to undergo screening mammography of the opposite breast , at the same cost , after the initial diagnosis of breast cancer . Table 2 . Information Used to Calculate Costs The cost of evaluating abnormal mammographic results was calculated as a weighted average of procedures that may follow abnormal mammograms . This cost was also inflated to 1995 dollars . The distribution and types of follow-up procedures were based on those reported by the National Cancer Institute 's National Survey of Mammography Facilities [ 35 ] . A range of costs for each procedure was based on data from Medicare , Pennsylvania Blue Cross , Group Health Cooperative , and Kaiser Permanente ( Brown M. Personal communication ) . The percentage of abnormal mammograms was based on the percentage seen with high- quality modern screening mammography ( Table 2 ) [ 36 ] . Population -based data on the cancer stage at diagnosis in screened compared with nonscreened women are sparse . OBJECTIVES This study was conducted to determine the incidence of physiologically significant coronary artery disease in a group of asymptomatic high risk men with essential hypertension and to assess the validity of noninvasive tests in a subset of these patients undergoing coronary arteriography . METHODS Two hundred twenty-six asymptomatic men ( mean age 61 + /- 8 years ) with essential hypertension and no clinical evidence of coronary artery disease but with at least one additional coronary risk factor were studied prospect ively . Fifty age- and risk factor-matched normotensive subjects were evaluated as a control group . After a minimum of 4 days without medication , subjects underwent stress thallium-201 scintigraphy , exercise and 48-h ambulatory electrocardiography , and echocardiography . Coronary angiography was performed in a subset of 34 ( 40 % ) of 84 patients with one or more positive test results . RESULTS A positive thallium-201 scintigram ( 18 % vs. 6 % ; odds ratio 3.4 , confidence interval 0.95 to 10.8 , p = 0.056 ) , exercise electrocardiograms ( ECGs ) ( 37 % vs. 13 % ; odds ratio 4.1 , confidence interval 1.5 to 11.2 , p < 0.003 ) and ambulatory ECG ( 15 % vs. 0 % , p < 0.05 ) were more common in the hypertensive group than in the control group . In the cohort undergoing coronary angiography , thallium-201 scintigraphy was both sensitive and specific for epicardial atherosclerotic coronary disease ( 90 % and 79 % , respectively ) , but positive exercise and ambulatory ECGs occurred frequently in the absence of significant coronary stenoses . In the 39 % of hypertensive patients who had mild to moderate left ventricular hypertrophy , positive exercise and ambulatory ECGs occurred at a higher rate . CONCLUSIONS These findings suggest that physiologically significant coronary artery disease occurs more frequently in asymptomatic hypertensive men than in comparable normotensive control subjects . In the subgroup undergoing coronary arteriography , reversible scintigraphic defects were both sensitive and specific for diagnosing epicardial coronary artery disease , but exercise and ambulatory ECGs appeared to yield frequent false positive results , especially when left ventricular hypertrophy was present . These results indicate that patients with " silent " coronary artery disease can be identified among high risk hypertensive patients , but the appropriate application of such screening in clinical practice remains to be determined BACKGROUND Previous reports have suggested that an attenuated exercise heart rate response may be associated with coronary heart disease risk and with mortality . These observations may parallel the association between reduced heart rate variability during normal activities and adverse outcome . This investigation was design ed to look at the prognostic implication s of exercise heart rate response in a population -based sample . METHODS AND RESULTS In this prospect i ve cohort investigation , 1575 male participants ( mean age , 43 years ) in the Framingham Offspring Study who were free of coronary heart disease , who were not taking beta-blockers , and who underwent submaximal treadmill exercise testing ( Bruce protocol ) were studied . Heart rate response was assessed in three ways : ( 1 ) failure to achieve 85 % of the age-predicted maximum heart rate , which has been the traditional definition of chronotropic incompetence ; ( 2 ) the actual increase in heart rate from rest to peak exercise ; and ( 3 ) the ratio of heart rate to metabolic reserve used by stage 2 of exercise ( " chronotropic response index " ) . Proportional hazards analyses were used to evaluate the associations of heart rate responses with all-cause mortality and with coronary heart disease incidence during 7.7 years of follow-up . Failure to achieve target heart rate occurred in 327 ( 21 % ) subjects . During follow-up there were 55 deaths ( 14 caused by coronary heart disease ) and 95 cases of incident coronary heart disease . Failure to achieve target heart rate , a smaller increase in heart rate with exercise , and the chronotropic response index were predictive of total mortality and incident coronary heart disease ( P < .01 ) . Failure to achieve target heart rate remained predictive of incident coronary heart disease even after adjusting for age , ST-segment response , physical activity , and traditional coronary disease risk factors ( adjusted hazard ratio , 1.75 ; 95 % confidence interval , 1.11 to 2.74 ; P=.02 ) . After adjusting for the same factors , the increase in exercise heart rate remained inversely predictive of total mortality ( P=.04 ) and coronary heart disease incidence ( P=.0003 ) . The chronotropic response index also was predictive of total mortality ( P=.05 ) and incident coronary heart disease ( P=.001 ) after adjusting for age and other risk factors . CONCLUSIONS An attenuated heart rate response to exercise , a manifestation of chronotropic incompetence , is predictive of increased mortality and coronary heart disease incidence Background —Exercise stress testing alone or with perfusion imaging is the st and ard screening method to determine the presence of obstructive coronary artery disease ( CAD ) in people with chest pain . In asymptomatic individuals with a family history of premature CAD , it is unclear whether abnormalities on these functional exercise tests represent significant coronary disease . Methods and Results —An abnormal exercise test , thallium scan , or both occurred in 153 ( 21 % ) of 734 asymptomatic siblings of persons with documented CAD , of whom 105 underwent coronary angiography with quantitative analysis of stenosis severity . Overall , 95 % had coronary atherosclerosis , but only 39 % had 1 or more stenoses with ≥50 % narrowing . Of 30 siblings in whom the exercise test and perfusion scan were both abnormal , 70 % had ≥50 % stenoses . The mean stenosis in arteries that fed perfusion defects was only 43±31 % , and 68 % of such stenoses were < 50 % . However , in 71 % of all defects , the location matched arteries with the most severe stenoses . Conclusions —In asymptomatic persons with a family history of CAD , abnormal exercise scintigraphy identifies predominantly mild coronary atherosclerosis . Perfusion defects may be caused by coronary vasomotor dysfunction in addition to atherosclerotic plaque We prospect ively studied 135 asymptomatic normotensive subjects with exercise-induced ST ischemic depression of 1 mm or more and compared them with 379 controls . At least two controls with negative responses on the exercise electrocardiographic ( EKG ) test were selected for each case and were matched for age , sex , work , community , and coronary-risk-factors index . The end points considered were the following coronary events : angina pectoris , myocardial infa rct ion , and sudden death . After a median follow-up period of 6.0 years for the cases and 6.4 years for the controls , the relative risk was 5.55 ( 95 per cent confidence limits , 2.75 to 11.22 ) . Coronary events occurred significantly earlier in the cases than in the controls . Our data also suggest that the exercise EKG response is a particularly good prognostic indicator for myocardial infa rct ion . In addition , our analysis has confirmed the predictive roles of age , smoking , blood pressure , and the coronary-risk-factors index and suggests that the exercise EKG response is an additional independent risk indicator for coronary events A positive exercise electrocardiogram ( ECG ) has been proved to predict cardiovascular events in asymptomatic normolipidemic men . To study whether it is also predictive for hypercholesterolemic men , data from 3,806 asymptomatic hypercholesterolemic men in the Lipid Research Clinics Coronary Primary Prevention Trial were analyzed . All the men had performed a submaximal treadmill exercise test at baseline , before they were assigned to the cholestyramine or placebo treatment group . Because of missing or inconclusive data , 31 men were excluded from the analyses . A test was positive if the ST segment was displaced by greater than or equal to 1 mm ( visual code ) or there was greater than or equal to 10 microV-s change in the ST integral ( computer code ) , or both . The prevalence of a positive test was 8.3 % . During the 7 to 10 year ( mean 7.4 ) follow-up period , the mortality rate from coronary heart disease was 6.7 % ( 21 of 315 ) in men with a positive test and 1.3 % ( 46 of 3,460 ) in men with a negative test ( placebo and cholestyramine groups combined ) . The age-adjusted rate ratio for a positive test , compared with a negative test , was 6.7 in the placebo group and 4.8 in the cholestyramine group . With use of Cox 's proportional hazards models , it was found that the risk of death from coronary heart disease associated with a positive test was 5.7 times higher in the placebo group and 4.9 times higher in the cholestyramine group after adjustment for age , smoking history , systolic blood pressure , high density lipoprotein cholesterol and low density lipoprotein cholesterol . A positive test was not significantly associated with nonfatal myocardial infa rct ion . ( ABSTRACT TRUNCATED AT 250 WORDS Hypertension and left ventricular ( LV ) hypertrophy are independent risk factors for the development of coronary artery disease . To determine whether patients at higher risk for coronary artery disease can be identified , 40 asymptomatic hypertensive men with LV hypertrophy were prospect ively studied using exercise thallium-201 scintigraphy and exercise radionuclide angiography . Endpoints indicative of coronary artery disease were defined as the subsequent development of typical angina pectoris , which occurred in 8 patients during a median follow-up of 38 months , or myocardial infa rct ion , which did not occur . The exercise electrocardiogram was interpreted by st and ard ST-segment criteria and by a computerized treadmill exercise score . Abnormal ST-segment responses were present in 16 of the 40 hypertensives ( 40 % ) , whereas the treadmill score was positive in 8 of those same 40 patients ( 20 % ) . Scintigraphic perfusion defects assessed both visually and semiquantitatively were observed in 8 of 40 ( 20 % ) patients . An abnormal ejection fraction response to exercise was present in 40 % ( 16 of 40 ) of patients , and 3 of 40 ( 7.5 % ) developed new wall motion abnormalities during exercise . Six of 8 patients with either perfusion defects or abnormal treadmill score developed typical angina during follow-up . All 5 patients with concordant positive exercise scintigrams and treadmill score developed chest pain during follow-up and had coronary artery disease confirmed by coronary angiography . However , only 7 of 16 ( 44 % ) patients with positive ST changes or abnormal ejection fraction responses during exercise developed chest pain during follow-up . In contrast , of 32 patients with negative scintigrams only 2 developed atypical chest pain syndromes , and significant coronary artery disease was excluded by angiography in 1 patient . ( ABSTRACT TRUNCATED AT 250 WORDS Exercise testing in asymptomatic persons has been criticized for failing to accurately predict those at risk for coronary heart disease ( CHD ) . Previous studies on asymptomatic subjects , however , may not have been large enough or long enough to provide reliable outcome measures . This study examines the ability of a maximal exercise test to predict death from CHD and death from any cause in a population of asymptomatic men . This is a prospect i ve longitudinal study performed between 1970 and 1989 , with an average follow-up of 8.4 years . The subjects are 25,927 healthy men , 20 to 82 years of age at baseline ( mean 42.9 years ) who were free of cardiovascular disease and who were evaluated in a preventive medicine clinic . The main outcome measures are CHD mortality and all-cause mortality . During follow-up there were 612 deaths from all causes and 158 deaths from CHD . The sensitivity of an abnormal exercise test to predict coronary death was 61 % . The age-adjusted relative risk of an abnormal exercise test for CHD death was 21 ( 6.9 to 63.3 ) in those with no risk factors , 27 ( 10.7 to 68.8 ) in those with 1 risk factor , 54 ( 21.5 to 133.7 ) in those with 2 risk factors , and 80 ( 30.0 to 212 . 5 ) in those with > /=3 factors . A maximal exercise test performed in asymptomatic men free of cardiovascular disease does appear to be a worthwhile tool in predicting future risk of CHD death . An abnormal exercise test is a more powerful predictor of risk in those with than without conventional risk factors In Leeds in hospital population s of patients with angina the maximal ST/HR slope was found to be a reliable index of myocardial ischemia as assessed by coronary angiography . Subsequent studies in Leeds and elsewhere in population s of patients with cardiac enlargement or following myocardial infa rct ion have shown that the slope is affected by myocardial scarring , ventricular enlargement and aneurysm . These findings implied that the slope had features in common with other usual exercise tests ; studies in Leeds and elsewhere , however , have shown a superior diagnostic reliability using the maximal ST/HR slope in patients with angina . The present report involves the use of the slope in asymptomatic population s. Trials are being undertaken in two factory population s , which respectively comprised all volunteers or asymptomatic men over the age of 30 who were r and omly chosen by computer . Subjects with slope values indicating , according to previous experience , myocardial ischemia equivalent to coronary heart disease were referred for cardiological investigations which included angiocardiography ; blind comparisons were performed between results of investigations and the slope . So far 1194 subjects have been examined . In 68 subjects the maximal ST/HR slope indicated myocardial ischemia , and in 24 of these cardiological investigations were completed . In nine of the 24 subjects the slope corresponded to the number of significantly narrowed coronary arteries ( greater than 75 % reduction in luminal diameter ) ; in 12 of the remaining 15 subjects who had no coronary narrowing , there were cardiac lesions which included cardiac enlargement , aortic valve disease , myocarditis , pericarditis , myocardial bridging and conduction defects . ( ABSTRACT TRUNCATED AT 250 WORDS This pilot study demonstrated that ( 1 ) patients with CAD and asymptomatic cardiac ischemia can be r and omized to medical or revascularization strategies using a complex and dem and ing protocol , ( 2 ) asymptomatic cardiac ischemia can be suppressed in 40 - 50 % of patients with clinical ly advanced coronary disease with relatively low to moderate doses of medication titrated over a period of 12 weeks ( 3 ) . Revascularization was the most effective of the treatment strategies studied in reducing ischemia . Any type of therapy , whether it be drugs or revascularization requiring repetitive monitoring with ambulatory ECG or other methods to detect ischemia over a long period of time , will escalate the cost of quality medical care for our patients . Thus , the health care costs implication s and treatment of asymptomatic ischemia are enormous . But the apparent cost advantage of treating only symptoms , that is ignoring all ischemia , could disappear if treatment of ischemia reduces the risk of adverse events . The clinical question to be addressed in the future is what is necessary to reduce the cardiac-event rates of death and myocardial infa rct ion in this group of patients ? Will more aggressive drug therapy eliminate more ischemia and will therapy directed at the elimination of all detectable ischemia improved clinical outcome better than therapy directed to control angina only ? These questions can only be answered by a large clinical trial . The results of such a trial will provide the basis and rationale for safe and effective therapy for patients with coronary disease and evidence of cardiac ischemia . Whatever the answer to this important medical and scientific question is , it will have tremendous economic implication s. ( ABSTRACT TRUNCATED AT 250 WORDS A 10 year prospect i ve community practice study in Seattle of risk of primary morbidity ( defined by hospital admission ) and mortality due to coronary heart disease in 3,611 men and 547 women initially free of clinical manifestations of this disease revealed a crude incidence of 202 coronary heart disease events , or 4.9 % in 6.1 + /- 2.6 years of follow-up . The case fatality rate was 16.8 % . Stratification by clinical classification of asymptomatic healthy persons versus patients with atypical chest pain syndrome ( not angina pectoris ) and hypertension ( as classified by physicians ) showed an incidence rate of primary events due to coronary heart disease of 2.9 , 5.5 ( not significant ) and 10.0 % ( p less than 0.001 ) , respectively . Identification of conventional risk factors is known to be important for risk assessment . However , the presence of any conventional risk factor , in conjunction with two or more selected maximal exercise predictors ( which vary with the clinical classification ) at enrollment , substantially increased the cumulative 6 year incidence rate to 24.3 , 15.5 and 33.3 % in asymptomatic healthy men , patients with atypical chest pain syndrome and hypertensive patients , respectively . Observation of the exercise predictors in the absence of conventional risk factors increased the risk much less , suggesting that the use of maximal exercise testing for risk assessment in those with no clinical manifestations of disease might be limited to persons with one or more conventional risk factors We determined whether the exercise electrocardiogram predicted acute cardiac events during moderate or strenuous physical activity among 3617 asymptomatic , hypercholesterolemic men ( age range , 35 to 59 years ) who were followed up in the Coronary Primary Prevention Trial . Submaximal exercise test results were obtained at entry and at annual follow-up visits in years 2 through 7 . ST-segment depression or elevation ( greater than or equal to 1 mm or 10 microV-sec ) was considered to be a positive test result . The circumstances that surrounded each nonfatal myocardial infa rct ion and coronary heart disease death were determined through a record review . The cumulative incidence of activity-related acute cardiac events was 2 % during a mean follow-up period of 7.4 years . The risk was increased 2.6-fold in the presence of clinical ly silent , exercise-induced , ST-segment changes at entry ( 95 % confidence interval [ Cl ] , 1.3 to 5.2 ) after adjustment for 11 other potential risk factors . Of 62 men who experienced an activity-related event , 11 had a positive test result at entry ( sensitivity , 18 % ; 95 % Cl , 8 to 27 ) . The specificity of the entry exercise test was 92 % ( 95 % Cl , 91 to 93 ) . The sensitivity and specificity were similar when the length of follow-up was restricted to 1 year after testing . For a newly positive test result on a follow-up visit , the sensitivity was 24 % ( 95 % Cl , 12 to 36 ) , and the specificity was 85 % ( 95 % Cl , 84 to 86 ) ; for any positive test result during the study ( mean number of tests per subject , 6.2 ) , the sensitivity was 37 % ( 95 % Cl , 25 to 49 ) , and the specificity was 79 % ( 95 % Cl , 77 to 80 ) . Our findings suggested that the presence of clinical ly silent , exercise-induced , ischemic ST-segment changes on a submaximal test was associated with an increased risk of activity-related acute cardiac events . However , this test was not sensitive when used to predict the occurrence of activity-related events among asymptomatic , hypercholesterolemic men . For this reason , the utility of the submaximal exercise test to assess the safety of physical activity among asymptomatic men at risk of coronary heart disease is likely to be limited We previously reported on the prognostic importance of heart rate recovery after symptom-limited exercise in an intermediate-risk group of patients who were referred for exercise testing with thallium single-photon emission computed tomography in a tertiary-care center ( 1 ) . It is unknown , however , whether these findings can be generalized to healthy adults undergoing submaximal exercise . Our goal was to examine heart rate recovery as a predictor of long-term mortality in a population -based cohort of adults without evidence of cardiovascular disease who underwent submaximal exercise testing . All-cause mortality was the outcome of interest because of its relevance and its objective and unbiased nature ( 2 ) . Methods The study cohort was derived from the Lipid Research Clinics Prevalence Study , the selection of which has been described in detail elsewhere ( 3 - 6 ) . Briefly , that study was design ed to determine the prevalence of lipid abnormalities among North Americans . Of the 68 317 population -based persons recruited from 10 primary care centers , those with lipid abnormalities ( approximately 10 % of the population ) and an additional r and omly selected 15 % were invited to undergo more extensive investigation ( 3 ) . Of the 13 852 who appeared for this second visit , 8681 underwent exercise testing . Reasons for exclusion from exercise testing included resting systolic blood pressure less than 90 or greater than 200 mm Hg , resting diastolic blood pressure greater than 120 mm Hg , inability to complete a treadmill test on the basis of physician examination , or participant request ( 5 , 6 ) . To assure selection of a cardiovascularly healthy asymptomatic cohort similar to that in previous population -based studies ( 7 ) , persons were excluded if they were younger than 30 years of age ( n=131 [ 2 % ] ) ; were taking -blockers , digoxin , antiarrhythmic agents , or nitrates ( n=356 [ 4 % ] ) ; had a history of cardiovascular disease ( defined as previous heart surgery or history of angina , myocardial infa rct ion , claudication , stroke , previous vascular surgery , congenital disease , or arrhythmia ) ( n=2413 [ 28 % ] ) ; or were unable to reach stage 2 of exercise ( n=1620 [ 19 % ] ) . Before testing , participants underwent a detailed medical and family history that elicited information about medical conditions , alcohol use , smoking , education level , socioeconomic status , exercise habits , and medications . Lipid profiles were obtained in all patients . The treadmill exercise protocol used was the Bruce or modified Bruce protocol ( 5 , 6 ) . Participants exercised until they attained at least 85 % to 90 % of their age- and fitness-predicted maximum heart rate for 1 minute or until fatigue or medical contraindications to continued exercise were observed . Data on symptoms , heart rate , and blood pressure were collected and electrocardiography was done before exercise , at the end of each stage , immediately after exercise , and 2 minutes into recovery . Estimated workload , expressed in metabolic equivalents , was based on total treadmill time . Chronotropic response during exercise was assessed by using the chronotropic indexthe ratio of heart rate to metabolic reserve usedduring stage 2 of exercise ( 8 , 9 ) . We used a cutoff value ( 0.86 ) that maximized the log-rank chi-square statistic ( 10 ) . Immediately after exercise , participants were helped to chairs , and recovery data were obtained . Heart rate recovery was defined as the change from peak heart rate to that measured after 2 minutes of recovery ( that is , heart rate recovery = heart ratepeak heart rate2-min recovery ) . An abnormal value for heart rate recovery was determined by finding the maximum value for the log-rank chi-square test statistic for all possible cutoff points between the 10th and 90th percentiles ( 10 ) ; this turned out to be 42 beats/min or less . This cutoff value differed from and could not be validly compared to that of our previous study ( 1 ) because 2-minute values ( rather than 1-minute values ) were used and because exercise was submaximal , not symptom-limited . We also considered indexing the 2-minute heart rate recovery by the maximum heart rate , but this result ed in a substantially lower maximum log-rank chi-square value ( 44 compared with 77 ) . Mean follow-up time was 12 years . The primary end point was all-cause mortality , which was determined through annual telephone interviews with study participants or their families or employers . Cause of death was assessed by review of death certificates and interviews of physicians or next of kin ( 6 ) . If the patient could not be contacted , registries were search ed for mortality information . For assessment of vital status , follow-up was 100 % complete . All analyses were performed by using version 6.12 of the SAS statistical package ( SAS Institute , Inc. , Cary , North Carolina ) . For descriptive purpose s , patients were divided into two groups based on heart rate recovery . Continuous variables are presented as the mean SD . Differences between groups were compared by using the Student t-test , Wilcoxon rank-sum test , and chi-square test , as appropriate . Heart rate recovery was related to all-cause mortality by using univariable and multivariable Cox regression analyses . Stratified analyses were performed on prespecified subgroups according to age , sex , exercise patterns , smoking , cholesterol level , resting blood pressure and heart rate , chronotropic response to exercise , and medication use . Logarithmic and quadratic transformations and potential interactions were assessed for improvement of fit ; the strata option of PROC PHREG was used to allow for accurate estimation of main effects relative risks . The Cox proportional-hazards assumption was confirmed by inspection of log ( log [ survival ] ) curves . Attributable risk was calculated as P ( RR 1)/[P ( RR 1 ) + 1 ] , where P is prevalence and RR is relative risk . The estimated actuarial survival rate for the population was estimated on the basis of data from 1985 U.S. life tables ( 11 ) . According to the policy at our institution , this research was considered exempt from institutional review board approval because it used existing , publically available data . In addition , the data were recorded in such a manner that participants could not be identified directly or through identifiers linked to them . Results Baseline and Exercise Characteristics A total of 5234 adults met all inclusion criteria . The median value for heart rate recovery was 49 beats/min ( 25th and 75th percentiles , 39 and 59 beats/min ) . An abnormal heart rate recovery of 42 beats/min or less was seen in 1715 participants ( 33 % ) . Baseline and exercise characteristics of the study participants according to heart rate recovery are summarized in Table 1 . Table 1 . Baseline and Exercise Characteristics according to Heart Rate Recovery after Exercise Heart Rate Recovery and Mortality During 12 years of follow-up , 325 patients ( 6.2 % ) died . According to U.S. life tables , the actuarial predicted death rate was 7 % . Abnormal heart rate recovery was strongly predictive of death ( 10 % compared with 4 % among participants with normal heart rate recovery ; relative risk , 2.58 [ 95 % CI , 2.06 to 3.20 ] ) ( P<0.001 ) . The sensitivity , specificity , and positive and negative predictive values of an abnormal heart rate recovery for prediction of death over 12 years were 54 % , 69 % , 10 % , and 96 % , respectively . Of the participants who died , 116 ( 36 % ) were thought to have died of cardiovascular causes . An abnormal heart rate recovery was even more strongly predictive of cardiovascular death than of death in general ( 4 % compared with 1 % ; relative risk , 3.06 [ CI , 2.10 to 4.44 ] ) ( P<0.001 ) . Results of analyses stratified by age , sex , chronotropic response to exercise , regular exercise , smoking , resting hemodynamics , cholesterol level , and use of vasodilator medication are shown in Table 2 . Abnormal heart rate recovery was predictive of death in all subgroups except participants taking vasodilators . Table 2 . Association of Abnormal Heart Rate Recovery with Mortality according to Prespecified Subgroups Multivariable Cox Regression Analyses After adjustment for age , sex , body mass index , ethnicity , resting systolic blood pressure , use of vasodilators , exercise habits , physical fitness , smoking , diabetes , lipid profiles , ST-segment response , resting heart rate , chronotropic index , and educational and socioeconomic status and after consideration of interaction terms , a slower decrease in heart rate remained predictive of death ( adjusted relative risk , 1.55 [ CI , 1.22 to 1.98 ] ) ( P<0.001 by chi-square test ) . The adjusted attributable risk for death related to abnormal heart rate recovery was 15 % ( CI , 7 % to 24 % ) . Abnormal heart rate recovery was also predictive of cardiovascular death after adjustment for potential confounders and interactions ( adjusted relative risk , 1.95 [ CI , 1.11 to 3.42 ] ) ( P=0.02 ) . Discussion Heart rate recovery after submaximal exercise was a powerful predictor of mortality in a population -based cohort of adults without clinical ly evident cardiovascular disease , even after we adjusted for multiple , potentially confounding factors . These findings confirm the results of our previous study ( 1 ) and exp and them by demonstrating the prognostic importance of heart rate recovery in healthy persons undergoing submaximal , as opposed to symptom-limited , exercise testing . Heart rate recovery may therefore be a clinical ly relevant predictor of risk among patients undergoing screening exercise testing . Furthermore , because an abnormal heart rate recovery accounted for 15 % of deaths , this measure may be useful for insurance underwriting assessment s. It has been suggested that the link between heart rate recovery and mortality may be related to vagal tone and physical fitness ( 12 ) . We also noted an association between fitness levels and recovery heart rate ; participants with abnormal heart rate recovery were less likely to exercise regularly and to participate in strenuous exercise ( Table 1 ) . It should be noted that heart rates |
12,822 | 18,541,188 | Evidence from these review s indicates that screening for breast cancer ( by mammography ) has been increased effectively by reducing structural barriers and by reducing out-of pocket client costs , and that screening for colorectal cancer ( by fecal occult blood test ) has been increased effectively by reducing structural barriers . | Most major medical organizations recommend routine screening for breast , cervical , and colorectal cancers .
Screening can lead to early detection of these cancers , result ing in reduced mortality .
Yet not all people who should be screened are screened , either regularly or , in some cases , ever . | BACKGROUND In 1994 , Oregon implemented the Oregon Health Plan ( OHP ) , extending health care coverage under a system of capitated managed care to uninsured citizens living below the Federal Poverty Level ( FPL ) . We conducted a study to measure receipt of clinical preventive services among women newly enrolled in the OHP . METHODS Six hundred and sixty six women aged 52 - 64 , and living below the FPL in Oregon were r and omly selected from OHP enrollment rosters and interviewed by telephone . A follow-up survey was conducted 1 year later . The main outcome of interest was receipt of a screening mammogram during the first year in the OHP . RESULTS At enrollment 17 % ( 65/383 ) of participants had never had health care coverage . Sixty-six percent of the women ( 220/333 ) were overdue for a mammogram . Fifty-five percent ( 121/220 ) reported cost as the main reason they had not had this procedure . Mammography rates doubled under the OHP ( 21 % to 52 % , 95 % CI = 0.25 - 0.38 , p < 0.001 ) . Among women who were overdue for a mammogram at the time they enrolled , an expressed plan to get a mammogram ( OR3.0 , 95 % CI = 1.1 - 8.7 , p = 0.04 ) , citing cost as the main reason for being overdue ( OR3.0 , 95 % CI = 1.3 - 7.2 , p = 0.014 ) , receipt of a routine checkup ( OR9.5 , 95%CI = 3.7 - 24.9 , p < 0.001 ) , and health care provider 's ( HCP 's ) recommendation for mammography ( OR8.1,95 % CI = 2.9 - 23.0 , p < 0.001 ) were independently associated with receipt of a mammogram . CONCLUSION The OHP enrolled and successfully delivered clinical preventive services to a medically under served population . Even after removing the financial barrier , obstacles to mammography remain . These may be overcome by health systems changes to insure receipt of routine checkups and appropriate provider recommendations Patient compliance in returning fecal-hemoccult card packets has been studied in recent years but no specific interventions have been shown consistently to improve the return rate . It was wondered whether removing a small financial barrier for indigent patients would positively affect compliance . Therefore , the effect of prepaid postage on the rate of return was studied . Pre-prepared packets containing hemoccult cards with return envelopes were distributed in a r and omized fashion to indigent and private insurance patients in outpatient clinics . On half of the return envelopes return postage was applied . The main outcome measure was the rate of return of stamped and unstamped packets stratified between indigent and private insurance patients . The overall rates of return were 117 of 159 ( 74 % ) for the stamped packets and 102 of 166 ( 61 % ) for unstamped packets ( p < 0.02 ) . After stratification , in the indigent patients ( n = 177 ) , 73 of 95 ( 77 % ) stamped packets were returned compared to 46 of 82 ( 56 % ) unstamped packets ( p < 0.006 ) . In the private insurance patients ( N = 148 ) , 44 of 64 stamped packets ( 69 % ) and 52 of 84 unstamped packets ( 62 % ) were returned ( p > 0.10 ) . Removing even small financial barriers ( eg , providing a postage stamp ) can enhance compliance for indigent patients Screening with the faecal occult blood test ( FOBT ) has been shown in r and omized control trials to be effective in reducing mortality from colorectal cancer . Compliance to this test recommendation , however , by the general population is usually low . To evaluate different methods of increasing compliance with FOBT , using mailed test kits or order cards , with or without information leaflets , subjects were r and omly assigned to receive a test kit or a kit request card . An information leaflet was included in half of the mailings . All participants were contacted for interview . Compliance was evaluated through the central computer system of the study 's FOBT laboratory . Self‐initiated compliance with FOBT in the year preceding the study was 0.6 % of the study participants . The overall compliance rate with the programme invitation was 17.9 % , with a somewhat higher , though non‐significant response to the mailed kit ( 19.9 % ) over the kit request card ( 15.9 % ) . Women complied with the test significantly more than men , older participants more than younger . Compliance to FOBT is low among the Israeli population aged 50–74 who receive a formal invitation to carry out this screening . Mailing a kit request card within the framework of a screening programme can achieve a substantial increase ( to 17.9 % ) in the level of compliance for the relatively low cost of postage . More effort is needed to study additional means of convincing the non‐responders to take part in this potentially life saving activity OBJECTIVE We conducted a cluster r and omized clinical trial to compare the benefit of offering on-site mobile mammography in addition to an outreach program design ed to increase mammography use by educating patients . SUBJECTS AND METHODS We recruited a consecutive volunteer sample of 499 women ranging in age from 60 to 84 years who had not undergone mammography in the previous year to participate in a cluster r and omized clinical trial about the benefit of on-site mobile mammography . Subjects were recruited from 60 community-based sites where seniors gather . The intervention included a structured on-site multicomponent educational program with or without available on-site mobile mammography . The primary outcome measure was self-reported receipt of mammography within 3 months of the intervention . RESULTS Women in the group offered access to on-site mammography and health education were significantly more likely than those in the group offered health education only to undergo mammography within 3 months ( 55 % vs 40 % , p = 0.001 ; adjusted [ for clustering ] odds ratio , 1.83 ; 95 % confidence interval , 1.22 - 2.74 ) . Gains from offering on-site mammography were shown for several ethnic and sociodemographic subgroups and were especially large for Asian American women . CONCLUSION Offering on-site mammography at community-based sites where older women gather is an effective method for increasing breast cancer screening rates among older women and may be particularly effective for some subgroups of women who traditionally have had low screening rates BACKGROUND We conducted a prospect i ve controlled clinical trial in an urban academic general medicine practice to test the effect of same-day mammography availability on adherence to physicians ' screening mammography recommendations . PATIENTS AND METHODS Participants were a consecutive sample of 920 female patients aged 50 years or older who had received a physician 's recommendation for screening mammography at an office visit and had no active breast symptoms , history of breast cancer , or a mammogram within the previous 12 months . Women were assigned to same-day screening mammography availability ( intervention group ) or usual screening mammography scheduling ( control group ) . MAIN OUTCOME MEASURES Three- , 6- , and 12-month rates of adherence to physicians ' recommendations for screening mammography . RESULT Twenty-six percent of women in the intervention group obtained a same-day screening mammogram . At 3 months , 58 % of the women in the intervention group underwent the recommended screening mammography compared with 43 % of the women in the control group ( P<.001 ) , increasing to 61 % and 49 % at 6 months ( P<.001 ) , and 268 ( 66 % ) of 408 vs 287 ( 56 % ) of 512 at 12 months ( P = .003 ) . The difference between the intervention and control groups 3-month adherence rates was most marked among women aged 65 years or older ( 58 % vs 34 % ; P<.001 ) , women who were not employed ( 54 % vs 36 % ; P<.001 ) , and women with a history of having had either no mammograms ( 39 % vs 20 % ; P = .02 ) or only 1 to 2 mammograms ( 57 % vs 38 % ; P<.001 ) within the last 5 years . CONCLUSIONS Same-day mammography availability increased 3- , 6- , and 12-month screening mammography adherence rates in this urban academic general medicine practice . The effect was most marked among women aged 65 years or older , women who were not employed , and those who had had fewer than 3 mammograms in the last 5 years . The efficacy of this intervention in other setting s still needs to be demonstrated BACKGROUND This study tested a breast cancer education intervention for African American women with poor screening histories . Disparities in rates of later-stage disease and death may be related to lower screening rates due to behavioral ( e.g. , knowledge gap ) and structural ( e.g. , access ) barriers . METHODS 94 African American women ( low-income , poor screening histories ) were r and omly assigned for an educational and on-site screening intervention , or non-intervention status . Primary care sites were used for educational purpose s. Three-month post-intervention mammography was assessed . RESULTS The intervention group had significantly higher screening rates than the non-intervention group . The latter had a knowledge gap , poor screening history , cancer fears , and insurance differences relative to the screened women . Screening was predicted by behavioral , rather than structural factors . CONCLUSIONS Since low-income African American women face behavioral and structural barriers to breast cancer screening , an educational program that improves knowledge levels and is offered in primary care sites can effectively impact screening BACKGROUND Although colorectal cancer screening by using a fecal occult blood test ( FOBT ) , flexible sigmoidoscopy , colonoscopy , or barium enema x-ray reduces the incidence of and death from colorectal cancer , the rate of colorectal cancer screening in the general population is low . We conducted a r and omized trial consisting of direct mailing of FOBT kits to increase colorectal cancer screening among residents of Wright County , Minnesota , a community in which colorectal cancer screening was promoted . METHODS At baseline , we mailed a question naire about colorectal cancer screening to a r and om sample of Wright County residents aged 50 years or older who were r and omly selected from the Minnesota State Driver 's License and Identification Card data base ( estimated N = 1451 ) . The sample was r and omly allocated into three equal subgroups : one group ( control ) received only the question naire , one group received FOBT kits by direct mail with reminders , and one group received FOBT kits by direct mail without reminders . Study participants were sent a follow-up question naire 1 year after baseline . We used the responses to the question naires to estimate the 1-year change in self-reported screening rates in each group and the differences in the changes among the groups , along with the associated bootstrap 95 % confidence intervals ( CIs ) . RESULTS At baseline , the estimated response rate was 86.5 % , self-reported adherence to FOBT guidelines was 21.5 % , and overall adherence to any colorectal cancer screening test guidelines was 55.8 % . The 1-year rate changes in absolute percentage for self-reported adherence to FOBT use were 1.5 % ( 95 % CI = -2.9 % to 5.9 % ) for the control group , 16.9 % ( 95 % CI = 11.5 % to 22.3 % ) for the direct-mail-FOBT-with-no-reminders group , and 23.2 % ( 95 % CI = 17.2 % to 29.3 % ) for the direct-mail-FOBT-with-reminders group . The 1-year rate changes for self-reported adherence to any colorectal cancer screening test were 7.8 % ( 95 % CI = 3.2 % to 12.0 % ) for the control group , 13.2 % ( 95 % CI = 8.4 % to 18.2 % ) for the direct-mail-FOBT-with-no-reminders group , and 14.1 % ( 95 % CI = 9.1 % to 19.1 % ) for the direct-mail-FOBT-with-reminders group . CONCLUSION Direct mailing of FOBT kits combined with follow-up reminders promotes more rapid increases in the use of FOBT and nearly doubles the increase in overall rate of adherence to colorectal cancer screening guidelines in a general population compared with a community-wide screening promotion and awareness campaign Research ers in migrant health clinics in Washington state found cost to be the single most commonly reported reason given by foreign-born Hispanic women for never having had a mammogram . The true significance of this finding beyond self-report was unknown . A r and omized intervention trial design ed to test the effect of fully subsidized mammograms on utilization was conducted within this population . Women in the intervention group received st and ard clinic instruction plus a voucher for a free mammogram . Controls received st and ard clinic instruction alone . Eighty-seven percent of women receiving vouchers obtained a mammogram within 30 days , compared with 17.5 % of controls . Logistic regression analysis revealed that women receiving vouchers were 47 times more likely to obtain a mammogram than controls . This confirms women 's self-report that cost is a major barrier to accessing screening mammograms in this low-income migrant population , and that women are more likely to utilize this service when financial barriers are removed When the GUIDE TO COMMUNITY PREVENTIVE SERVICES : Systematic Review s and Evidence -Based Recommendations ( the Guide ) is published in 2001 , it will represent a significant national effort in encouraging evidence -based public health practice in defined population s ( e.g. , communities or members of specific managed care plans ) . The Guide will make recommendations regarding public health interventions to reduce illness , disability , premature death , and environmental hazards that impair community health and quality of life . The Guide is being developed under the guidance of the Task Force on Community Preventive Services ( the Task Force)-a 15-member , nonfederal , independent panel of experts . Subject matter experts , method ologists , and scientific staff are supporting the Task Force in using explicit rules to conduct systematic literature review s of evidence of effectiveness , economic efficiency , and feasibility on which to base recommendations for community action . Contributors to the Guide are building on the experience of others to confront method ologic challenges unique to the assessment of complex multicomponent intervention studies with nonexperimental or nonr and omized design s and diverse measures of outcome and effectiveness . Persons who plan , fund , and implement population -based services and policies to improve health at the state and local levels are invited to scrutinize the work in progress and to communicate with contributors . When the Guide is complete , readers are encouraged to consider critically the value and relevance of its contents , the implementation of interventions the Task Force recommends , the ab and onment of interventions the Task Force does not recommend , and the need for rigorous evaluation of the benefits and harms of promising interventions of unknown effectiveness PURPOSE / OBJECTIVES To test the effectiveness of a community-based intervention to increase mammography screening for Korean American women . DESIGN Quasi-experimental , pre-/post-test , three-group design . SETTING Urban Korean American communities in Southern California . SAMPLE 141 Korean American women , aged 40 - 75 , who had not had a mammogram in the previous 12 months . METHOD Two Korean churches were selected r and omly to be study sites that would provide health screening programs . The study included an experimental group that would have access to a peer-group educational program and low-cost mammography , a group that would have access to low-cost mammography alone , and a control group . Participant-focused strategies were used to involve Korean American women from the community . MAIN RESEARCH VARIABLES Mammography use , breast cancer screening attitudes , and knowledge . FINDINGS Women in the experimental program had significantly improved attitudes and knowledge about breast cancer screening . Mammography use in the experimental group ( 87 % ) was not significantly different from that in the mammography-access-only group ( 72 % ) . Both interventions proved to be more effective than no intervention at all ( control group = 47 % ) . CONCLUSIONS An educational program that includes participant-focused research strategies and access to low-cost mammograms result ed in higher levels of screening . IMPLICATION S FOR NURSING Community-focused interventions can increase rates of cancer screening among Korean American women BACKGROUND This r and omized trial evaluated the impact of mammography-enhancing interventions implemented in 40 senior citizens ' housing facilities in Pennsylvania and North Carolina . METHODS After stratification of the facilities according to the socioeconomic status and racial background s of their residents , they were r and omly assigned to one of four groups to receive the following : 1 ) st and ard care -- a Medicare mammography benefit flier ; 2 ) education -- the flier and a community education program ; 3 ) access -- the flier , mammography appointments , and transportation ; 4 ) combined -- all interventions . Telephone surveys , conducted prior to any intervention , identified mammography-eligible women , who were re-surveyed six months later to ascertain mammography use . RESULTS Logistic regression analyses identified mammography intention , age , and the interaction between ever having had mammography and being in the combined intervention group to be significant predictors of mammography use at six months . However , no significant main effect was found for any of the interventions . CONCLUSIONS These results suggest that the combination of community-directed mammography education and access to mammography appointments encourages mammography use primarily by women who are already predisposed to having mammography . However , individually targeted and tailored interventions may be needed to encourage mammography use among women who have never had mammography and /or express no intention of having it done A r and omized controlled trial to test patient compliance with screening for colorectal cancer in association with general practice health checks was carried out in six practice s ( three urban and three rural ) . A total of 1588 patients aged 45 - 64 years were r and omized to one of four intervention groups . In the first group patients were posted a Haemoccult test ( Kline Beckman ) kit . This group was not invited for a health check . In the second group patients were posted the Haemoccult test kit , together with an invitation to attend for a health check . In the third group patients were posted an invitation for a health check , which explained that the patient would be offered the Haemoccult test kit by the nurse at the health check . In the fourth group patients were just invited for a health check . It was found that combining faecal occult blood testing with the health check did not reduce attendance at the health check--43.5 % of patients attended when the Haemoccult test kit was offered by the nurse at the health check , 43.6 % attended when a test kit was included with the invitation to attend the health check and 42.9 % attended when the health check invitation was posted on its own . Overall , compliance with Haemoccult testing was not significantly increased by associating it with a health check ( 26.2 % versus 25.5 % ) but compliance was higher when the faecal occult blood testing kit was enclosed with the health check invitation than when it was offered at the health check ( 31.7 % versus 20.6 % , P less than 0.001 ) . It is easier and cheaper to combine various screening procedures . Although the overall use of the Haemoccult test in the study population was low , there is no reason why the relatively higher compliance rate obtained on posting the test kit with a health check invitation can not be achieved in previously unscreened population s with higher expected compliance rates . However , faecal occult blood screening for colorectal cancer should not be undertaken on a population basis until its effectiveness in reducing mortality has been proven by r and omized trial Mammography use decreases with age although the risk of breast cancer increases with age . Medicare now provides biennial coverage for screening mammography . This study was design ed to simulate the Medicare condition by subsidizing mammography among women in eight retirement communities in the metropolitan Philadelphia area . The study also measured the impact of health education interventions and the presence of a mobile mammography van on increased use of mammography . Retirement communities were assigned r and omly to the control ( cost subsidy alone ) or experimental group ( cost subsidy , mammography van , and tailored health education interventions ) . A total of 412 women ages 65 and older who had not had mammograms in the previous year were surveyed at baseline and 3 months later . Analytic techniques reflected the cluster nature of the r and omization . Women in the experimental group were significantly more likely than the control group women to have obtained mammograms . Forty-five percent of the experimental group women compared with 12 percent of the control group women subsequently had mammograms in the 3 months after the baseline interview ( P less than .001 ) . Logistic regression analysis for mammography use indicated an odds ratio of 6.1 associated with being in the experimental group . For women in the experimental group , a separate logistic regression for mammography use showed an odds ratio of 7.8 associated with attendance at the educational presentation . The results suggest that Medicare coverage alone will not increase mammography use sufficiently to achieve year 2000 objectives . However , the addition of access enhancing and health education interventions boosts utilization dramatically Colorectal cancer is a life threatening , yet treatable , disease . Although early detection can improve health outcomes and preserve quality of life , many people are not screened . A post-test experimental design was used to test an intervention to increase screening behavior among eighty-one family practice patients , aged 50 - 70 . Subjects were given a brief talk and a packet of educational material s. The physician recommended that each person complete a screening test at home . The experimental group was given a free screening test . The utilization rate in the experimental group was 51 % compared to 0 % in the control group . Findings suggest free kits encourage more use ; yet further exploration is needed to explain non-use , even when free kits are provided . Recommendations for future social work practice and research are discussed This study aim ed to examine whether knowledge , attitudes and concerns predicted attendance at the mobile Breast X-Ray Programme in Sydney . A cohort study design was used , whereby women were surveyed prior to the implementation of the program , and two years later records were checked to determine whether they had attended for screening . Telephone interviews were sought with r and omly selected women aged 45 to 70 years living in the central Sydney area ( the screening van 's catchment area ) . A total of 285 women was surveyed ( response rate : 50 per cent ) . Of these , 86 ( 30 per cent ) subsequently attended at the mobile van and 199 did not . Attendance did not appear to be related to any of the following factors : knowledge ; attitudes ; prior experience ; perceived susceptibility and morbid concern in relation to breast cancer ; the amount of information about screening mammography to which a woman had been exposed . The results are interpreted in light of method ological considerations plus findings from our other research Poor patient adherence reduces the effectiveness of fecal occult blood testing for colon cancer . Patients at the inner-city clinic involved in the study have historically completed only one-third of the tests administered to them . The authors studied three ways of returning test kits ( by h and , by mail , and by mail with prepaid postage ) . Among 146 r and omly assigned patients , the completion rates were 37 % , 57 % , and 71 % , respectively . The difference was significant between the first and third groups ( p=0.003 ) , and the cost was less for the third group ( $ 1.71 vs $ 2.24 per completed test ) . The authors recommend that clinics serving indigent population s use postage-paid return envelopes with fecal occult blood testing to improve its effectiveness and save money OBJECTIVE In January 1991 , Medicare extended its mammography benefit to reimburse for breast cancer screening mammograms . In 1991 and again in 1993 , the National Cancer Institute Breast Cancer Screening Consortium ( BCSC ) conducted a survey to test the hypothesis that this benefit would increase mammography use among women over the age of 65 . METHODS The authors analyzed data on non-Hispanic white women ages 65 to 74 living in 11 geographic areas targeted by the BCSC for an earlier study --six that had received cancer screening educational interventions and five control subsites -- to measure the impact of the newly adopted Medicare benefit on the use of mammography and use of Medicare to reimburse mammography costs . RESULTS The data show little overall increase between 1991 and 1993 in reported mammography use among respondents to the survey . However , in six intervention and five control subsites there was an increase in the percentage of women who reported using public payment sources to at least partially reimburse the cost of mammograms . In three intervention subsites , the increase from 1991 to 1993 in the percentage of women using public sources of payment was greater than in the corresponding control subsites . CONCLUSIONS These findings suggest that public health interventions are more likely to succeed when educational promotion accompanies a financial benefit BACKGROUND In 1991 , Medicare began covering screening mammograms subject to copayment and deductible . This study evaluated the effectiveness of Medicare in removing financial barriers to screening mammography among low-income older women . METHODS In an inner-city public hospital 's General Medicine Clinic , 119 consecutive , eligible , and consenting Medicare-enrolled women without known risk factors for breast cancer other than age , and no mammogram in the previous 2 years , were entered into a r and omized controlled trial with follow-up after 2 months . The mean age was 71 years ; 77 % were black , 92 % had an annual income below $ 10,000 , and 52 % had had a previous mammogram . All patients were counseled concerning indications for screening mammograms and Medicare coverage , and all were referred to a low-cost mammography facility . Sixty-one subjects were r and omly assigned a voucher for a free screening mammogram at the referral facility . Obtaining a mammogram within 60 days of study entry was the main outcome measure . RESULTS Of the women given vouchers , 27 ( 44 % ) obtained screening mammograms , compared with six ( 10 % ) of those without vouchers ( P < .001 ) . Adjustment by multiple logistic regression confirmed this association , yielding an adjusted odds ratio of 7.4 ( 95 % confidence interval , 2.5 to 21.4 ) . Knowledge concerning mammography and breast cancer increased significantly overall ( and within r and omization groups ) between initial interview and follow-up ; fear did not change . For women without the voucher , the main reason for not obtaining a mammogram was financial ; the main reason for women with the voucher was transportation . CONCLUSION In a low-income , inner-city population of older women , financial barriers to screening mammography persist despite Medicare coverage |
12,823 | 17,415,595 | At present there is no evidence that one type of treatment is clearly superior to others , including no treatment , for patients with a lumbosacral radicular syndrome | Patients with a lumbosacral radicular syndrome are mostly treated conservatively first .
The effect of the conservative treatments remains controversial .
To assess the effectiveness of conservative treatments of the lumbosacral radicular syndrome ( sciatica ) . | Abstract This single-blind r and omised clinical trial compared osteopathic manipulative treatment with chemonucleolysis ( used as a control of known efficacy ) for symptomatic lumbar disc herniation . Forty patients with sciatica due to this diagnosis ( confirmed by imaging ) were treated either by chemonucleolysis or manipulation . Outcomes ( leg pain , back pain and self-reported disability ) were measured at 2 weeks , 6 weeks and 12 months . The mean values for all outcomes improved in both groups . By 12 months , there was no statistically significant difference in outcome between the treatments , but manipulation produced a statistically significant greater improvement for back pain and disability in the first few weeks . A similar number from both groups required additional orthopaedic intervention ; there were no serious complications . Crude cost analysis suggested an overall financial advantage from manipulation . Because osteopathic manipulation produced a 12-month outcome that was equivalent to chemonucleolysis , it can be considered as an option for the treatment of symptomatic lumbar disc herniation , at least in the absence of clear indications for surgery . Further study into the value of manipulation at a more acute stage is warranted The management of sciatica due to lumbar nerve root compromise remains controversial , probably because few well-controlled studies of conservative management have been performed . This preliminary study assesses the efficacy of epidural injections of 80 mg triamcinolone acetonide plus 0.5 % procaine hydrochloride in saline , administered via the caudal route , in a double-blind , placebo controlled trial with 1 year follow-up . Twenty-three patients were entered into the study : 12 received treatment and 11 placebo . The active group showed significant pain relief ( P=0.02 ) and a significant increase in mobility ( P=0.01 ) at 4 weeks , which result ed in improved quality of life ( P=0.02 ) . At 1 year , subjective and objective measures improved in both groups . The improvement was greater in the actively treated group , but only the objective assessment ( straight leg raise ) was statistically significant BACKGROUND Although epidural corticosteroid injections are commonly used for sciatica , their efficacy has not been established . METHODS In a r and omized , double-blind trial , we administered up to three epidural injections of methylprednisolone acetate ( 80 mg in 8 ml of isotonic saline ) or isotonic saline ( 1 ml ) to 158 patients with sciatica due to a herniated nucleus pulposus . All patients had Oswestry disability scores higher than 20 ( on a scale of 1 to 100 , with scores of 20 or less indicating minimal disability , and higher scores greater disability ) . RESULTS At three weeks , the Oswestry score had improved by a mean of -8.0 in the methylprednisolone group and -5.5 in the placebo group ( 95 percent confidence interval for the difference , -7.1 to 2.2 ) . Differences in improvements between the groups were not significant , except for improvements in the finger-to-floor distance ( P=0.006 ) and sensory deficits ( P=0.03 ) , which were greater in the methylprednisolone group . After six weeks , the only significant difference was the improvement in leg pain , which was greater in the methylprednisolone group ( P=0.03 ) . After three months , there were no significant differences between the groups . The Oswestry score had improved by a mean of -17.3 in the methylprednisolone group and -15.4 in the placebo group ( 95 percent confidence interval for the difference , -9.3 to 5.4 ) . At 12 months , the cumulative probability of back surgery was 25.8 percent in the methylprednisolone group and 24.8 percent in the placebo group ( P=0.90 ) . CONCLUSIONS Although epidural injections of methylprednisolone may afford short-term improvement in leg pain and sensory deficits in patients with sciatica due to a herniated nucleus pulposus , this treatment offers no significant functional benefit , nor does it reduce the need for surgery This study reports on 105 patients with acute low-back pain given tizanidine ( 4 mg three times daily ) plus ibuprofen ( 400 mg three times daily ) or placebo plus ibuprofen ( 400 mg three times daily ) . Patients assessed their pain using visual analogue scales in a daily diary and the doctor assessed their condition at baseline and on days 3 and 7 . Both groups were treated effectively , but earlier improvement occurred in patients given tizanidine/ibuprofen , particularly regarding pain at night and at rest . Doctors assessed the helpfulness of treatment : tizanidine/ibuprofen was significantly better than placebo/ibuprofen at day 3 ( P = 0.05 ) . Significant differences between treatments in favour of tizanidine/ibuprofen occurred in patients with moderate and severe pain at night ( P<0.05 ) , at rest ( P<0.05 ) and those with moderate or severe sciatica ( P<0.05 ) . Significantly more patients given placebo/ibuprofen had gastro-intestinal side-effects compared with tizanidine/ibuprofen ( P = 0.002 ) . This supports previous work in animals showing that tizanidine mediates gastric mucosal protection against anti-inflammatory drugs . More patients given tizanidine/ibuprofen suffered drowsiness and other central nervous system effects ( P = 0.025 ) . In patients with severe acute low-back pain , however , some sedation and bed rest is advantageous . This study shows that tizanidine/ibuprofen is more effective in the treatment of moderate or severe acute low-back pain than placebo and ibuprofen alone The effect of extradural corticosteroid injection in patients with nerve root compression syndromes associated with degenerative disease of the lumbar intervertebral discs was assessed in a double-blind controlled trial on 100 consecutive in patients assigned by r and om allocation to treatment and control groups . Assessment during admission and at three months revealed statistically highly significant differences in respect of relief of pain and resumption of normal occupation in favour of the group treated by extradural injection . This treatment seems to be a valuable adjunct to the management of lumbar nerve root compression syndromes associated with degenerative disc disease The value of epidural injections of corticosteroid as an outpatient treatment of sciatica has been hitherto uncertain . An epidural injection of 80 mg methylprednisolone in 10 ml physiological saline was compared with an interspinous injection of 2 ml physiological saline in a double blind fashion amongst 39 out patients . Significant differences of pain relief were seen between the two groups within 2 weeks . This benefit disappeared for six ( 35 % ) patients within 6 months of treatment although 11 ( 65 % ) successfully treated subjects had sustained improvement up to this time . Outpatient epidural injections of corticosteroid are thus a useful short-term means of relieving pain in sciatica but probably have little effect on the long-term natural history of symptoms . Factors associated with a failure to respond to epidural steroid injections are discussed Four treatment regimens for patients with specified combinations of low back pain and sciatica were evaluated . The largest group studied had low back pain with limited straight-leg raising ( SLR ) and in them the beneficial effect of manipulation in hastening pain relief was highly significant . In similar patients without limitation of SLR , the effect was of borderline significance . In all the other groups , treated patients also recovered more quickly than their controls . Traction , for patients with low back pain and sciatica , and epidural injections when a root palsy was present also produced some significant pain relief . The effect of sclerosants for back pain was less clear OBJECT The authors conducted a study to compare the efficacies of three nonsurgical treatment strategies in patients with sciatica . Their hypothesis was that bed rest , physiotherapy , and continuation of activities of daily living ( ADLs ) ( control treatment ) are each of equivalent efficacy . METHODS This r and omized controlled trial was design ed for comparison of bed rest , physiotherapy , and continuation of ADLs . The setting was an outpatient clinic . General practitioners were asked to refer patients for treatment as soon as possible . The authors enrolled 250 patients ( < 60 years of age ) with sciatica of less than 1-month 's duration and who had not yet been treated with bed rest or physiotherapy . Primary outcome measures were radicular pain ( based on a visual analog pain scale [ VAPS ] ) and hampered ADLs ( Quebec Disability Scale [ QDS ] ) . Secondary outcome measures were the rates of treatment-related failure and surgical treatment . Measures were assessed at baseline and during follow up at 1 , 2 , and 6 months . Mean differences in VAPS and QDS scores between bed rest and control treatment were 2.5 ( 95 % confidence interval [ CI ] -6.4 to 11.4 ) and -4.8 ( 95 % CI -10.6 to 0.9 ) at 1 month and 0.9 ( 95 % CI -8.7 to 10.4 ) and -2.7 ( 95 % CI -9.9 to 4.4 ) at 2 months , respectively . The respective differences between physiotherapy and control treatment were 0.8 ( 95 % CI -8.2 to 9.8 ) and -0.5 ( 95 % CI -6.3 to 5.3 ) at 1 month and -0.3 ( 95 % CI -9.4 to 10 ) and 0.0 ( 95 % CI -7.2 to 7.3 ) at 2 months . The respective odds ratios for treatment failure and surgical treatment of bed rest compared with control treatment were 1.6 ( 95 % CI 0.8 - 3.5 ) and 1.5 ( 95 % CI 0.7 - 3.6 ) at 6 months . When physiotherapy was compared with control treatment , these ratios were 1.5 ( 95 % CI 0.7 - 3.2 ) and 1.2 ( 95 % CI 0.5 - 2.9 ) at 6 months , respectively . CONCLUSIONS Bed rest and physiotherapy are not more effective in acute sciatica than continuation of ADLs Most systematic review s rely substantially on the assessment of the method ological quality of the individual trials . The aim of this study was to obtain consensus among experts about a set of generic core items for quality assessment of r and omized clinical trials ( RCTs ) . The invited participants were experts in the field of quality assessment of RCTs . The initial item pool contained all items from existing criteria lists . Subsequently , we reduced the number of items by using the Delphi consensus technique . Each Delphi round comprised a question naire , an analysis , and a feedback report . The feedback report included staff team decisions made on the basis of the analysis and their justification . A total of 33 international experts agreed to participate , of whom 21 completed all question naires . The initial item pool of 206 items was reduced to 9 items in three Delphi rounds . The final criteria list ( the Delphi list ) was satisfactory to all participants . It is a starting point on the way to a minimum reference st and ard for RCTs on many different research topics . This list is not intended to replace , but rather to be used alongside , existing criteria lists A prospect i ve , r and omised , double-blind study was carried out to compare the respective efficacies of transforaminal and interspinous epidural corticosteroid injections in discal radiculalgia . Thirty-one patients ( 18 females , 13 males ) with discal radicular pain of less than 3 months ’ duration were consecutively r and omised to receive either radio-guided transforaminal or blindly performed interspinous epidural corticosteroid injections . Post-treatment outcome was evaluated clinical ly at 6 and 30 days , and then at 6 months , but only by mailed question naire . At day 6 , the between-group difference was significantly in favour of the transforaminal group with respect to Schober ’s index , finger-to-floor distance , daily activities , and work and leisure activities on the Dallas pain scale . At day 30 , pain relief was significantly better in the transforaminal group . At month 6 , answers to the mailed question naire still showed significantly better results for transforaminal injection concerning pain , daily activities , work and leisure activities and anxiety and depression , with a decline in the Rol and –Morris score . In recent discal radiculalgia , the efficacy of radio-guided transforaminal epidural corticosteroid injections was higher than that obtained with blindly-performed interspinous injections Study Design . A r and omized , double-blind trial was conducted . Objectives . To test the efficacy of periradicular corticosteroid injection for sciatica . Summary of Background Data . The efficacy of epidural corticosteroids for sciatica is controversial . Periradicular infiltration is a targeted technique , but there are no r and omized controlled trials of its efficacy . Methods . In this study 160 consecutive , eligible patients with sciatica who had unilateral symptoms of 1 to 6 months duration , and who never underwent surgery were r and omized for double-blind injection with methylprednisolone bupivacaine combination or saline . Objective and self-reported outcome parameters and costs were recorded at baseline , at 2 and 4 weeks , at 3 and 6 months , and at 1 year . Results . Recovery was better in the steroid group at 2 weeks for leg pain ( P = 0.02 ) , straight leg raising ( P = 0.03 ) , lumbar flexion ( P = 0.05 ) , and patient satisfaction ( P = 0.03 ) . Back pain was significantly lower in the saline group at 3 and 6 months ( P = 0.03 and 0.002 , respectively ) , and leg pain at 6 months ( 13.5 , P = 0.02 ) . Sick leaves and medical costs were similar for both treatments , except for cost of therapy visits and drugs at 4 weeks , which were in favor of the steroid injection ( P = 0.05 and 0.005 , respectively ) . By 1 year , 18 patients in the steroid group and 15 in the saline group underwent surgery . Conclusions . Improvement during the follow-up period was found in both the methylprednisolone and saline groups . The combination of methylprednisolone and bupivacaine seems to have a short-term effect , but at 3 and 6 months , the steroid group seems to experience a “ rebound ” phenomenon BACKGROUND AND METHODS Bed rest is widely advocated for sciatica , but its effectiveness has not been established . To study the effectiveness of bed rest in patients with a lumbosacral radicular syndrome of sufficient severity to justify treatment with bed rest for two weeks , we r and omly assigned 183 subjects to either bed rest or watchful waiting for this period . The primary outcome measures were the investigator 's and patient 's global assessment s of improvement after 2 and 12 weeks , and the secondary outcome measures were changes in functional status and in pain scores ( after 2 , 3 , and 12 weeks ) , absenteeism from work , and the need for surgical intervention . Neither the investigators who assessed the outcomes nor those involved in data entry and analysis were aware of the patients ' treatment assignments . RESULTS After two weeks , 64 of the 92 patients in the bed-rest group ( 70 percent ) reported improvement , as compared with 59 of the 91 patients in the control ( watchful-waiting ) group ( 65 percent ) ( adjusted odds ratio for improvement in the bed-rest group , 1.2 ; 95 percent confidence interval , 0.6 to 2.3 ) . After 12 weeks , 87 percent of the patients in both groups reported improvement . The results of assessment s of the intensity of pain , the bothersomeness of symptoms , and functional status revealed no significant differences between the two groups . The extent of absenteeism from work and rates of surgical intervention were similar in the two groups . CONCLUSIONS Among patients with symptoms and signs of a lumbosacral radicular syndrome , bed rest is not a more effective therapy than watchful waiting 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 Schober 's index and spinal stiffness are shown in table II . Although both treatments produced significant improvement in pain , the improvement was more constant in the tiaprofenic acid group . Both treatments also produced beneficial effects when measured by Lassegue 's sign and finger to floor distances . In the case of the latter , tiaprofenic acid again appeared to be more effective but there was no statistically significant difference between the 2 treatments . Schober 's index also showed a similar result . For spinal stiffness , measured on a scale of 0 to 4 , there was no significant difference between the treatments . Addit ional ' relief analgesics were used on 4 occasions in the tiaprofenic acid group and 7 occasions in the alclofenac group . With regard to tolerance , 2 patients in the tiaprofenic acid group complained of side effects , I of generalised pruritus requiring discontinuation of treatment and the other of pain at the time of injection . In comparison , 4 patients in the alclofenac group complained of side effects . In 2 cases the treatment had to be discontinued due to an A r and omized trial of lumbar epidural injections for the treatment of acute sciatic pain was carried out . All the patients had unilateral sciatica for less than six months and had never previously been treated in hospital for their backs . The treatments used were 20 ml normal saline , 80 mg Depomedrone in normal saline made up to 20 ml , 20 ml , 20 ml 0.25 % bupivacaine solution and needling with a st and ard Touhy injection needle into the interspinous ligament but with no injection . The patients improved at about the same rate for all four treatments . Overall , 75 % of the patients improved or were cured . As some of these were in the group treated by needling of the interspinous ligament , it seems likely that the epidural injections administered achieved effects partially as a placebo and partially by virtue of the natural history of the acute sciatic syndrome Forty-nine patients with lumbago-sciatica and prolapsed lumbar intervertebral discs , comparable concerning anamnestical and clinical data were r and omized for autotraction and manual traction given by the same therapist for a period of one week while strict bed rest was prescribed . A blind overall assessment performed immediately after the traction period , after two weeks follow-up training and three months after hospitalization showed that the two traction modalities are equally efficient . As treatment for hospitalized patients with lumbar intervertebral disc prolapses the relatively simple manual traction variety should be preferred , if any . Traction is suggested to be used as a prognostical aid . Pain intensity was significantly reduced in all body parts . About one fourth of patients avoided operation . After two years there was no recurrence of symptoms Seventy-three patients with lumbar radicular pain syndromes were treated in a prospect i ve , r and omized , double-blind fashion with either seven milliliters of methylprednisolone acetate and procaine or seven milliliters of physiological saline solution and procaine . All patients had radiographic confirmation of lumbar nerve-root compression , consistent with the clinical diagnosis of either an acute herniated nucleus pulposus or spinal stenosis . No statistically significant difference was observed between the control and experimental patients with either acute disc herniation or spinal stenosis . Long-term follow-up , averaging twenty months , failed to demonstrate the efficacy of a second injection of epidural steroids administered to the patients whose pain did not respond within twenty-four hours to an injection of either eighty milligrams of methylprednisolone acetate combined with five milliliters of 1 per cent procaine or two milliliters of sterile saline combined with five milliliters of 1 per cent procaine . Therefore , a decision to use epidural steroids must be made with the realization that we failed to demonstrate its clinical efficacy in this study and that reports of serious complications of this procedure have been published In this prospect i ve r and omized clinical trial , the results of epidural corticosteroid injections were evaluated in patients with lumbosciatic pain caused by herniated nucleus pulposus . Thirty-six patients with radicular lumbosciatic pain and positive straight leg raising test because of confirmed prolapsed intervertebral lumbar discs were r and omized into two groups with ( 17 patients ) and without ( 19 patients ) epidural corticosteroid injection . Members of the treatment groups received three injections of 100 mg methylprednisolone in 10 mL bupivacaine 0.25 % each . Additional therapy was st and ardized and identical in both groups . Followup examinations were performed at 2 weeks , 6 weeks , and 6 months . The examinations included pain level ( visual analogue scale ) , straight leg raising test , and functional status ( Hannover Functional Ability Question naire ) . At 2 weeks , patients receiving methylprednisolone injection showed a significant improvement in straight leg raising test results compared with patients in the control group . Results were better in the methylprednisolone group , although not statistically significant for pain relief and mobility . At 6 weeks and 6 months , pain relief , improvement of straight leg raising , and improvement of functional status showed no statistical significance . Epidural corticosteroid injections can be recommended as additional therapy only in the acute phase of the conservative management of lumbosciatic pain A double-blind control study of lumbar traction for sciatica has been carried out . Although there is a tendency for traction to produce improvement in pain and straight-leg raise the extent does not achieve statistical significance . Changing ' control ' patients to ' treatment ' seemed to produce worthwhile relief of pain for all who were not already improving . It is suggested that a large trial using more discriminating criteria might delineate a group of patients susceptible to help by traction Two hundred eighty patients with herniated lumbar discs , verified by radiculography , were divided into three groups . One group , which mainly will be dealt with in this paper , consisted of 126 patients with uncertain indication for surgical treatment , who had their therapy decided by r and omization which permitted comparison between the results of surgical and conservative treatment . Another group comprising 67 patients had symptoms and signs that beyond doubt , required surgical therapy . The third group of 87 patients was treated conservatively because there was no indication for operative intervention . Follow-up examinations in the first group were performed after one , four , and ten years . The controlled trial showed a statistically significant better result in the surgically treated group at the one-year follow-up examination . After four years the operated patients still showed better results , but the difference was no longer statistically significant . Only minor changes took place during the last six years of observation A double blind study was carried out in 51 patients suffering from lumbar root compression syndrome of 12 days to 36 weeks duration . All patients had signs , symptoms and radiological abnormalities related to a herniated lumbar disc . Each patient received an extradural injection of either 2 ml ( 80 mg ) methyl prednisolone or 2 ml normal saline solution . Neurological examination and interview of the patients with the aid of a question naire before and after extradural injection failed to demonstrate any statistically significant difference in outcome between the two groups . At follow-up 14 + /- 6 months after extradural injection 58.3 per cent of the patients in the control group and 51.9 per cent of the patients in the treatment group had undergone surgical treatment with laminectomy . Our results indicate that a single extradural injection of methyl prednisolone ( 80 mg ) is no more effective than a placebo injection in relieving chronic symptoms due to myelographically demonstrable lumbar disc herniation In this controlled prospect i ve study of the Auto-traction method for the treatment of lumbago-sciatica , 82 patients were r and omly allocated to either treatment with Auto-traction for up to three 1-hour sessions in 1 week , or they were given a corset and advised to rest . The orthopaedic surgeons participating in the study worked at six different hospitals and all had limited experience of the Auto-traction method obtained during a 1-week course . All patients were clinical ly evaluated by an independent observer who also performed the follow-up examinations 1 and 3 weeks after the treatment sessions . In addition a 3-month follow-up was performed by letter . The Auto-traction method gave prompt relief of pain and a normalizing of the SLR test more often than treatment with only a corset and rest . The difference between the two treatment groups was statistically significant . The immediate difference noted between the treatment groups had decreased slightly at 3 weeks but was still statistically significant at this time |
12,824 | 26,020,382 | Importantly , the association of the mutations with the 3 clinical outcomes for serum was similar to that for tumor tissue and higher than that for plasma .
Blood , in particular serum , is a good substitute when tumor tissue is absent or insufficient for testing EGFR mutations to guide EGFR TKIs treatment in patients with NSCLC . | Abstract Tumor tissues are often absent or insufficient for testing epidermal growth factor receptor ( EGFR ) mutations to guide EGFR tyrosine kinase inhibitors ( TKIs ) treatment of patients with nonsmall cell lung cancer (NSCLC).We conducted this systematic review and meta- analysis to assess whether blood can be used as a substitute for tumor tissue in detecting EGFR mutations . | BACKGROUND We conducted a r and omized , placebo-controlled , double-blind trial to determine whether the epidermal growth factor receptor inhibitor erlotinib prolongs survival in non-small-cell lung cancer after the failure of first-line or second-line chemotherapy . METHODS Patients with stage IIIB or IV non-small-cell lung cancer , with performance status from 0 to 3 , were eligible if they had received one or two prior chemotherapy regimens . The patients were stratified according to center , performance status , response to prior chemotherapy , number of prior regimens , and prior platinum-based therapy and were r and omly assigned in a 2:1 ratio to receive oral erlotinib , at a dose of 150 mg daily , or placebo . RESULTS The median age of the 731 patients who underwent r and omization was 61.4 years ; 49 percent had received two prior chemotherapy regimens , and 93 percent had received platinum-based chemotherapy . The response rate was 8.9 percent in the erlotinib group and less than 1 percent in the placebo group ( P<0.001 ) ; the median duration of the response was 7.9 months and 3.7 months , respectively . Progression-free survival was 2.2 months and 1.8 months , respectively ( hazard ratio , 0.61 , adjusted for stratification categories ; P<0.001 ) . Overall survival was 6.7 months and 4.7 months , respectively ( hazard ratio , 0.70 ; P<0.001 ) , in favor of erlotinib . Five percent of patients discontinued erlotinib because of toxic effects . CONCLUSIONS Erlotinib can prolong survival in patients with non-small-cell lung cancer after first-line or second-line chemotherapy PURPOSE To evaluate the efficacy and tolerability of two doses of gefitinib ( Iressa [ ZD1839 ] ; AstraZeneca , Wilmington , DE ) , a novel epidermal growth factor receptor tyrosine kinase inhibitor , in patients with pretreated advanced non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS This was a r and omized , double-blind , parallel-group , multicenter phase II trial . Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens ( at least one containing platinum ) were r and omly assigned to receive either 250-mg or 500-mg oral doses of gefitinib once daily . RESULTS Efficacy was similar for the 250- and 500-mg/d groups . Objective tumor response rates were 18.4 % ( 95 % confidence interval [ CI ] , 11.5 to 27.3 ) and 19.0 % ( 95 % CI , 12.1 to 27.9 ) ; among evaluable patients , symptom improvement rates were 40.3 % ( 95 % CI , 28.5 to 53.0 ) and 37.0 % ( 95 % CI , 26.0 to 49.1 ) ; median progression-free survival times were 2.7 and 2.8 months ; and median overall survival times were 7.6 and 8.0 months , respectively . Symptom improvements were recorded for 69.2 % ( 250 mg/d ) and 85.7 % ( 500 mg/d ) of patients with a tumor response . Adverse events ( AEs ) at both dose levels were generally mild ( grade 1 or 2 ) and consisted mainly of skin reactions and diarrhea . Drug-related toxicities were more frequent in the higher-dose group . Withdrawal due to drug-related AEs was 1.9 % and 9.4 % for patients receiving gefitinib 250 and 500 mg/d , respectively . CONCLUSION Gefitinib showed clinical ly meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients . At 250 mg/d , gefitinib had a favorable AE profile . Gefitinib 250 mg/d is an important , novel treatment option for patients with pretreated advanced NSCLC [ corrected Purpose : Elevated levels or increases in circulating tumor cells ( CTC ) portend poor prognosis in patients with epithelial cancers . Less is known about CTCs as surrogate endpoints or their use for predictive biomarker evaluation . This study investigated the utility of CTC enumeration and characterization using the Cell Search platform , as well as mutation detection in circulating tumor DNA ( ctDNA ) , in patients with advanced non – small cell lung cancer ( NSCLC ) . Experimental Design : Forty-one patients were enrolled in a single-arm phase II clinical trial of erlotinib and pertuzumab . Peripheral blood was analyzed for CTC enumeration , EGFR expression in CTCs , and detection of oncogenic mutations in CTCs and ctDNA . Changes in CTC levels were correlated with 2[18F]fluoro-2-deoxy-d-glucose – positron emission tomographic ( FDG-PET ) and computed tomographic ( CT ) imaging and survival endpoints . Results : CTCs were detected ( ≥1 CTC ) at baseline in 78 % of patients . Greater sensitivity for mutation detection was observed in ctDNA than in CTCs and detected mutations were strongly concordant with mutation status in matched tumor . Higher baseline CTC counts were associated with response to treatment by Response Evaluation Criteria in Solid Tumors ( RECIST , P = 0.009 ) and decreased CTC counts upon treatment were associated with FDG-PET and RECIST response ( P = 0.014 and P = 0.019 ) and longer progression-free survival ( P = 0.050 ) . Conclusion : These data provide evidence of a correlation between decreases in CTC counts and radiographic response by either FDG-PET or RECIST in patients with advanced NSCLC . These findings require prospect i ve validation but suggest a potential role for using CTC decreases as an early indication of response to therapy and ctDNA for real-time assessment of mutation status from blood . Clin Cancer Res ; 18(8 ) ; 2391–401 . © 2012 AACR CONTEXT More persons in the United States die from non-small cell lung cancer ( NSCLC ) than from breast , colorectal , and prostate cancer combined . In pre clinical testing , oral gefitinib inhibited the growth of NSCLC tumors that express the epidermal growth factor receptor ( EGFR ) , a mediator of cell signaling , and phase 1 trials have demonstrated that a fraction of patients with NSCLC progressing after chemotherapy experience both a decrease in lung cancer symptoms and radiographic tumor shrinkages with gefitinib . OBJECTIVE To assess differences in symptomatic and radiographic response among patients with NSCLC receiving 250-mg and 500-mg daily doses of gefitinib . DESIGN , SETTING , AND PATIENTS Double-blind , r and omized phase 2 trial conducted from November 2000 to April 2001 in 30 US academic and community oncology centers . Patients ( N = 221 ) had either stage IIIB or IV NSCLC for which they had received at least 2 chemotherapy regimens . INTERVENTION Daily oral gefitinib , either 500 mg ( administered as two 250-mg gefitinib tablets ) or 250 mg ( administered as one 250-mg gefitinib tablet and 1 matching placebo ) . MAIN OUTCOME MEASURES Improvement of NSCLC symptoms ( 2-point or greater increase in score on the summed lung cancer subscale of the Functional Assessment of Cancer Therapy-Lung [ FACT-L ] instrument ) and tumor regression ( > 50 % decrease in lesion size on imaging studies ) . RESULTS Of 221 patients enrolled , 216 received gefitinib as r and omized . Symptoms of NSCLC improved in 43 % ( 95 % confidence interval [ CI ] , 33%-53 % ) of patients receiving 250 mg of gefitinib and in 35 % ( 95 % CI , 26%-45 % ) of patients receiving 500 mg . These benefits were observed within 3 weeks in 75 % of patients . Partial radiographic responses occurred in 12 % ( 95 % CI , 6%-20 % ) of individuals receiving 250 mg of gefitinib and in 9 % ( 95 % CI , 4%-16 % ) of those receiving 500 mg . Symptoms improved in 96 % of patients with partial radiographic responses . The overall survival at 1 year was 25 % . There were no significant differences between the 250-mg and 500-mg doses in rates of symptom improvement ( P = .26 ) , radiographic tumor regression ( P = .51 ) , and projected 1-year survival ( P = .54 ) . The 500-mg dose was associated more frequently with transient acne-like rash ( P = .04 ) and diarrhea ( P = .006 ) . CONCLUSIONS Gefitinib , a well-tolerated oral EGFR-tyrosine kinase inhibitor , improved disease-related symptoms and induced radiographic tumor regressions in patients with NSCLC persisting after chemotherapy Purpose : Activating mutations in the epidermal growth factor receptor ( EGFR ) are associated with enhanced response to EGFR tyrosine kinase inhibitors in non-small cell lung cancer ( NSCLC ) , whereas KRAS mutations translate into poor patient outcomes . We hypothesized that analysis of plasma for EGFR and KRAS mutations from shed tumor DNA would have clinical utility . Methods : An allele-specific polymerase chain reaction assay using Scorpion-amplification refractory mutation system ( DxS , Ltd ) was used to detect mutations in plasma DNA from patients with advanced stage NSCLC treated as second- or third-line therapy on a phase I/II trial of docetaxel plus intercalated erlotinib . Results : EGFR mutations were detected in 10 of 49 patients ( 20 % ) . Six ( 12 % ) had single activating mutations in EGFR , associated with improved progression-free survival ( median , 18.3 months ) , compared with all other patients ( median , 3.9 months ; p = 0.008 ) , or those with wild-type EGFR ( median , 4.0 months ; p = 0.012 ) . Four of 49 patients harbored a de novo T790 M resistance mutation ( median progression-free survival , 3.9 months ) . EGFR mutational status was associated with clinical response ( 45 assessable , p = 0.0001 ) ; in the six patients with activating mutations , all achieved complete ( 33 % ) or partial ( 67 % ) response . All CR patients had E19del detectable in both tumor and plasma . KRAS mutations were detected in two of 49 ( 4 % ) patients , both of whom had rapid progressive disease . Conclusions : Activating EGFR mutations detected in shed DNA in plasma are significantly associated with favorable outcomes in patients with advanced NSCLC receiving docetaxel plus intercalated erlotinib . The addition of docetaxel in this schedule did not diminish the efficacy of erlotinib against patients with EGFR activating mutations Introduction : In IPASS ( IRESSA Pan-Asia Study ) , clinical ly selected patients with pulmonary adenocarcinoma received first-line gefitinib or carboplatin/paclitaxel . This preplanned , exploratory analysis was conducted to increase underst and ing of the use of surrogate sample s , such as serum , versus tumor biopsy sample s for determining EGFR mutation status in the Japanese cohort ( n = 233 ) . Methods : EGFR mutations were assessed using tumor tissue-derived DNA ( n = 91 ) and circulating free ( cf ) DNA from pretreatment serum sample s ( n = 194 ) . Results : Fewer patients were EGFR mutation positive when assessed using pretreatment cfDNA ( 23.7 % ) versus tumor tissue-derived DNA ( 61.5 % ) . cfDNA results identified no false positives but a high rate of false negatives ( 56.9 % ) . There was a significant interaction between cfDNA EGFR mutation status and treatment for progression-free survival ( PFS ) ( p = 0.045 ) . PFS was significantly longer and objective response rate ( ORR ) higher with gefitinib than carboplatin/paclitaxel in the cfDNA EGFR mutation-positive subgroup ( PFS : hazard ratio [ HR ] , 0.29 ; 95 % confidence interval [ CI ] , 0.14–0.60 ; p < 0.001 ; ORR : odds ratio [ OR ] , 1.71 ; 95 % CI , 0.48–6.09 ; 75.0 % versus 63.6 % ; p = 0.40 ) . There was a slight numerical advantage in PFS and ORR for gefitinib over carboplatin/paclitaxel in the cfDNA EGFR mutation-negative subgroup , likely due to the high rate of false negatives within this subgroup . Conclusions : These results merit further investigation to determine whether alternative sources of tumor DNA , such as cfDNA in serum , could be used for determining EGFR mutation status in future ; currently , where a sample is available , analysis of tumor material is recommended BACKGROUND Patients with non-small-cell lung cancer harbouring mutations in the epidermal growth factor receptor ( EGFR ) gene respond well to the EGFR-specific tyrosine kinase inhibitor gefitinib . However , whether gefitinib is better than st and ard platinum doublet chemotherapy in patients selected by EGFR mutation is uncertain . METHODS We did an open label , phase 3 study ( WJTOG3405 ) with recruitment between March 31 , 2006 , and June 22 , 2009 , at 36 centres in Japan . 177 chemotherapy-naive patients aged 75 years or younger and diagnosed with stage IIIB/IV non-small-cell lung cancer or postoperative recurrence harbouring EGFR mutations ( either the exon 19 deletion or L858R point mutation ) were r and omly assigned , using a minimisation technique , to receive either gefitinib ( 250 mg/day orally ; n=88 ) or cisplatin ( 80 mg/m(2 ) , intravenously ) plus docetaxel ( 60 mg/m(2 ) , intravenously ; n=89 ) , administered every 21 days for three to six cycles . The primary endpoint was progression-free survival . Survival analysis was done with the modified intention-to-treat population . This study is registered with UMIN ( University Hospital Medical Information Network in Japan ) , number 000000539 . FINDINGS Five patients were excluded ( two patients were found to have thyroid and colon cancer after r and omisation , one patient had an exon 18 mutation , one patient had insufficient consent , and one patient showed acute allergic reaction to docetaxel ) . Thus , 172 patients ( 86 in each group ) were included in the survival analyses . The gefitinib group had significantly longer progression-free survival compared with the cisplatin plus docetaxel goup , with a median progression-free survival time of 9.2 months ( 95 % CI 8.0 - 13.9 ) versus 6.3 months ( 5.8 - 7.8 ; HR 0.489 , 95 % CI 0.336 - 0.710 , log-rank p<0.0001 ) . Myelosuppression , alopecia , and fatigue were more frequent in the cisplatin plus docetaxel group , but skin toxicity , liver dysfunction , and diarrhoea were more frequent in the gefitinib group . Two patients in the gefitinib group developed interstitial lung disease ( incidence 2.3 % ) , one of whom died . INTERPRETATION Patients with lung cancer who are selected by EGFR mutations have longer progression-free survival if they are treated with gefitinib than if they are treated with cisplatin plus docetaxel . FUNDING West Japan Oncology Group ( WJOG ) : a non-profit organisation supported by unrestricted donations from several pharmaceutical companies PURPOSE Mutations in the epidermal growth factor receptor ( EGFR ) kinase domain can predict tumor response to tyrosine kinase inhibitors ( TKIs ) in non-small-cell lung cancer ( NSCLC ) . However , obtaining tumor tissues for mutation analysis is challenging . We hypothesized that plasma-based EGFR mutation analysis is feasible and has value in predicting tumor response in patients with NSCLC . PATIENTS AND METHODS Plasma DNA sample s and matched tumors from 230 patients with stages IIIB to IV NSCLC were analyzed for EGFR mutations in exons 19 and 21 by using denaturing high-performance liquid chromatography . We compared the mutations in the plasma sample s and the matched tumors and determined an association between EGFR mutation status and the patients ' clinical outcomes prospect ively . RESULTS In 230 patients , we detected 81 EGFR mutations in 79 ( 34.3 % ) of the patients ' plasma sample s. We detected the same mutations in 63 ( 79.7 % ) of the matched tumors . Sixteen plasma ( 7.0 % ) and fourteen tumor ( 6.1 % ) sample s showed unique mutations . The mutation frequencies were significantly higher in never-smokers and in patients with adenocarcinomas ( P = .012 and P = .009 , respectively ) . In the 102 patients who failed platinum-based treatment and who were treated with gefitinib , 22 ( 59.5 % ) of the 37 with EGFR mutations in the plasma sample s , whereas only 15 ( 23.1 % ) of the 65 without EGFR mutations , achieved an objective response ( P = .002 ) . Patients with EGFR mutations had a significantly longer progression-free survival time than those without mutations ( P = .044 ) in plasma . CONCLUSION EGFR mutations can be reliably detected in plasma DNA of patients with stages IIIB to IV NSCLC and can be used as a biomarker to predict tumor response to TKIs Background : The authors evaluate the efficacy and safety of gefitinib monotherapy in chemotherapy-naive patients with advanced non – small-cell lung cancer ( NSCLC ) . A secondary endpoint is to evaluate the relationship between clinical manifestations and epidermal growth factor receptor ( EGFR ) mutation status . Methods : Japanese chemotherapy-naive NSCLC patients were enrolled . They had measurable lesions , Eastern Cooperative Oncology Group performance status of 0 to 2 , and adequate organ and bone marrow function . Patients received 250 mg of oral gefitinib daily . EGFR mutations in exon 18 , 19 , and 21 of DNA extracted from tumor and serum were analyzed by genomic polymerase chain reaction and direct sequence . Results : All 30 patients were eligible for the assessment of efficacy and safety . An objective response and stable disease were observed in 10 patients ( 33.3 % ) and nine patients ( 30.0 % ) , respectively . The median time to progression was 3.3 months and the median overall survival was 10.6 months . The 1-year survival rate was 43.3 % . Grade 3 toxicities were observed in seven patients . EGFR mutation was observed in four of 13 ( 30.8 % ) tumors , and two of them achieved partial response . In serum sample s , three of 10 patients with EGFR mutations in the serum before treatment had a response to gefitinib . EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment sample s from patients with a partial response or stable disease than in those from patients with progressive disease ( p = 0.006 ) . Conclusions : Gefitinib monotherapy in chemotherapy-naive NSCLC patients was active , with acceptable toxicities . These results warrant further evaluation of gefitinib monotherapy as a first-line therapy . The EGFR mutation in serum DNA may be a biomarker for monitoring the response to gefitinib during treatment |
12,825 | 30,787,594 | Conclusion Atezolizumab has a considerable potential in treating cancers with an acceptable risk profile | Purpose Immune checkpoint inhibitors have developed rapidly and have demonstrated antitumor activity in various cancers .
To evaluate the safety and efficacy of atezolizumab in treating cancers , we conducted this meta- analysis . | BACKGROUND We assessed the efficacy and safety of programmed cell death 1 ( PD-1 ) inhibition with pembrolizumab in patients with advanced non-small-cell lung cancer enrolled in a phase 1 study . We also sought to define and vali date an expression level of the PD-1 lig and 1 ( PD-L1 ) that is associated with the likelihood of clinical benefit . METHODS We assigned 495 patients receiving pembrolizumab ( at a dose of either 2 mg or 10 mg per kilogram of body weight every 3 weeks or 10 mg per kilogram every 2 weeks ) to either a training group ( 182 patients ) or a validation group ( 313 patients ) . We assessed PD-L1 expression in tumor sample s using immunohistochemical analysis , with results reported as the percentage of neoplastic cells with staining for membranous PD-L1 ( proportion score ) . Response was assessed every 9 weeks by central review . RESULTS Common side effects that were attributed to pembrolizumab were fatigue , pruritus , and decreased appetite , with no clear difference according to dose or schedule . Among all the patients , the objective response rate was 19.4 % , and the median duration of response was 12.5 months . The median duration of progression-free survival was 3.7 months , and the median duration of overall survival was 12.0 months . PD-L1 expression in at least 50 % of tumor cells was selected as the cutoff from the training group . Among patients with a proportion score of at least 50 % in the validation group , the response rate was 45.2 % . Among all the patients with a proportion score of at least 50 % , median progression-free survival was 6.3 months ; median overall survival was not reached . CONCLUSIONS Pembrolizumab had an acceptable side-effect profile and showed antitumor activity in patients with advanced non-small-cell lung cancer . PD-L1 expression in at least 50 % of tumor cells correlated with improved efficacy of pembrolizumab . ( Funded by Merck ; KEYNOTE-001 Clinical Trials.gov number , NCT01295827 . ) BACKGROUND Atezolizumab is a humanised antiprogrammed death-lig and 1 ( PD-L1 ) monoclonal antibody that inhibits PD-L1 and programmed death-1 ( PD-1 ) and PD-L1 and B7 - 1 interactions , reinvigorating anticancer immunity . We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer . METHODS We did a r and omised , open-label , phase 3 trial ( OAK ) in 194 academic or community oncology centres in 31 countries . We enrolled patients who had squamous or non-squamous non-small-cell lung cancer , were 18 years or older , had measurable disease per Response Evaluation Criteria in Solid Tumors , and had an Eastern Cooperative Oncology Group performance status of 0 or 1 . Patients had received one to two previous cytotoxic chemotherapy regimens ( one or more platinum based combination therapies ) for stage IIIB or IV non-small-cell lung cancer . Patients with a history of autoimmune disease and those who had received previous treatments with docetaxel , CD137 agonists , anti-CTLA4 , or therapies targeting the PD-L1 and PD-1 pathway were excluded . Patients were r and omly assigned ( 1:1 ) to intravenously receive either atezolizumab 1200 mg or docetaxel 75 mg/m2 every 3 weeks by permuted block r and omisation ( block size of eight ) via an interactive voice or web response system . Co primary endpoints were overall survival in the intention-to-treat ( ITT ) and PD-L1-expression population TC1/2/3 or IC1/2/3 ( ≥1 % PD-L1 on tumour cells or tumour-infiltrating immune cells ) . The primary efficacy analysis was done in the first 850 of 1225 enrolled patients . This study is registered with Clinical Trials.gov , number NCT02008227 . FINDINGS Between March 11 , 2014 , and April 29 , 2015 , 1225 patients were recruited . In the primary population , 425 patients were r and omly assigned to receive atezolizumab and 425 patients were assigned to receive docetaxel . Overall survival was significantly longer with atezolizumab in the ITT and PD-L1-expression population s. In the ITT population , overall survival was improved with atezolizumab compared with docetaxel ( median overall survival was 13·8 months [ 95 % CI 11·8 - 15·7 ] vs 9·6 months [ 8·6 - 11·2 ] ; hazard ratio [ HR ] 0·73 [ 95 % CI 0·62 - 0·87 ] , p=0·0003 ) . Overall survival in the TC1/2/3 or IC1/2/3 population was improved with atezolizumab ( n=241 ) compared with docetaxel ( n=222 ; median overall survival was 15·7 months [ 95 % CI 12·6 - 18·0 ] with atezolizumab vs 10·3 months [ 8·8 - 12·0 ] with docetaxel ; HR 0·74 [ 95 % CI 0·58 - 0·93 ] ; p=0·0102 ) . Patients in the PD-L1 low or undetectable subgroup ( TC0 and IC0 ) also had improved survival with atezolizumab ( median overall survival 12·6 months vs 8·9 months ; HR 0·75 [ 95 % CI 0·59 - 0·96 ] ) . Overall survival improvement was similar in patients with squamous ( HR 0·73 [ 95 % CI 0·54 - 0·98 ] ; n=112 in the atezolizumab group and n=110 in the docetaxel group ) or non-squamous ( 0·73 [ 0·60 - 0·89 ] ; n=313 and n=315 ) histology . Fewer patients had treatment-related grade 3 or 4 adverse events with atezolizumab ( 90 [ 15 % ] of 609 patients ) versus docetaxel ( 247 [ 43 % ] of 578 patients ) . One treatment-related death from a respiratory tract infection was reported in the docetaxel group . INTERPRETATION To our knowledge , OAK is the first r and omised phase 3 study to report results of a PD-L1-targeted therapy , with atezolizumab treatment result ing in a clinical ly relevant improvement of overall survival versus docetaxel in previously treated non-small-cell lung cancer , regardless of PD-L1 expression or histology , with a favourable safety profile . FUNDING F. Hoffmann-La Roche Ltd , Genentech , The development of human cancer is a multistep process characterized by the accumulation of genetic and epigenetic alterations that drive or reflect tumour progression . These changes distinguish cancer cells from their normal counterparts , allowing tumours to be recognized as foreign by the immune system . However , tumours are rarely rejected spontaneously , reflecting their ability to maintain an immunosuppressive microenvironment . Programmed death-lig and 1 ( PD-L1 ; also called B7-H1 or CD274 ) , which is expressed on many cancer and immune cells , plays an important part in blocking the ‘ cancer immunity cycle ’ by binding programmed death-1 ( PD-1 ) and B7.1 ( CD80 ) , both of which are negative regulators of T-lymphocyte activation . Binding of PD-L1 to its receptors suppresses T-cell migration , proliferation and secretion of cytotoxic mediators , and restricts tumour cell killing . The PD-L1–PD-1 axis protects the host from overactive T-effector cells not only in cancer but also during microbial infections . Blocking PD-L1 should therefore enhance anticancer immunity , but little is known about predictive factors of efficacy . This study was design ed to evaluate the safety , activity and biomarkers of PD-L1 inhibition using the engineered humanized antibody MPDL3280A . Here we show that across multiple cancer types , responses ( as evaluated by Response Evaluation Criteria in Solid Tumours , version 1.1 ) were observed in patients with tumours expressing high levels of PD-L1 , especially when PD-L1 was expressed by tumour-infiltrating immune cells . Furthermore , responses were associated with T-helper type 1 ( TH1 ) gene expression , CTLA4 expression and the absence of fractalkine ( CX3CL1 ) in baseline tumour specimens . Together , these data suggest that MPDL3280A is most effective in patients in which pre-existing immunity is suppressed by PD-L1 , and is re-invigorated on antibody treatment Purpose BIRCH was design ed to examine the efficacy of atezolizumab , a humanized anti-programmed death-lig and 1 ( PD-L1 ) monoclonal antibody , in advanced non-small-cell lung cancer ( NSCLC ) across lines of therapy . Patients were selected on the basis of PD-L1 expression on tumor cells ( TC ) or tumor-infiltrating immune cells ( IC ) . Patients and Methods Eligible patients had advanced-stage NSCLC , no CNS metastases , and zero to two or more lines of prior chemotherapy . Patients whose tumors expressed PD-L1 using the SP142 immunohistochemistry assay on ≥ 5 % of TC or IC ( TC2/3 or IC2/3 [ TC or IC ≥ 5 % PD-L1-expressing cells , respectively ] ) were enrolled . Atezolizumab 1,200 mg was administered intravenously every 3 weeks . Efficacy-evaluable patients ( N = 659 ) comprised three cohorts : first line ( cohort 1 ; n = 139 ) ; second line ( cohort 2 ; n = 268 ) ; and third line or higher ( cohort 3 ; n = 252 ) . The primary end point was independent review facility-assessed objective response rate ( ORR ; Response Evaluation Criteria in Solid Tumors [ RECIST ] version 1.1 ) . Secondary end points included median duration of response , progression-free survival , and overall survival ( OS ) . Results BIRCH met its primary objective of demonstrating a significant ORR versus historical controls . With a minimum of 12 months of follow-up , the independent review facility-assessed ORR was 18 % to 22 % for the three cohorts , and 26 % to 31 % for the TC3 or IC3 subgroup ; most responses are ongoing . Responses occurred regardless of EGFR or KRAS mutation status . The median OS from an up date d survival analysis ( minimum of 20 month follow up ) for cohort 1 was 23.5 months ( 26.9 months for TC3 or IC3 patients ) ; the median OS in cohorts 2 and 3 was 15.5 and 13.2 months , respectively . The safety profile was similar across cohorts and consistent with previous atezolizumab monotherapy trials . Conclusion BIRCH demonstrated responses with atezolizumab monotherapy in patients with PD-L1-selected advanced NSCLC , with good tolerability . PD-L1 status may serve as a predictive biomarker for identifying patients most likely to benefit from atezolizumab BACKGROUND Outcomes are poor for patients with previously treated , advanced or metastatic non-small-cell lung cancer ( NSCLC ) . The anti-programmed death lig and 1 ( PD-L1 ) antibody atezolizumab is clinical ly active against cancer , including NSCLC , especially cancers expressing PD-L1 on tumour cells , tumour-infiltrating immune cells , or both . We assessed efficacy and safety of atezolizumab versus docetaxel in previously treated NSCLC , analysed by PD-L1 expression levels on tumour cells and tumour-infiltrating immune cells and in the intention-to-treat population . METHODS In this open-label , phase 2 r and omised controlled trial , patients with NSCLC who progressed on post-platinum chemotherapy were recruited in 61 academic medical centres and community oncology practice s across 13 countries in Europe and North America . Key inclusion criteria were Eastern Cooperative Oncology Group performance status 0 or 1 , measurable disease by Response Evaluation Criteria In Solid Tumors version 1.1 ( RECIST v1.1 ) , and adequate haematological and end-organ function . Patients were stratified by PD-L1 tumour-infiltrating immune cell status , histology , and previous lines of therapy , and r and omly assigned ( 1:1 ) by permuted block r and omisation ( with a block size of four ) using an interactive voice or web system to receive intravenous atezolizumab 1200 mg or docetaxel 75 mg/m(2 ) once every 3 weeks . Baseline PD-L1 expression was scored by immunohistochemistry in tumour cells ( as percentage of PD-L1-expressing tumour cells TC3≥50 % , TC2≥5 % and < 50 % , TC1≥1 % and < 5 % , and TC0<1 % ) and tumour-infiltrating immune cells ( as percentage of tumour area : IC3≥10 % , IC2≥5 % and < 10 % , IC1≥1 % and < 5 % , and IC0<1 % ) . The primary endpoint was overall survival in the intention-to-treat population and PD-L1 subgroups at 173 deaths . Biomarkers were assessed in an exploratory analysis . We assessed safety in all patients who received at least one dose of study drug . This study is registered with Clinical Trials.gov , number NCT01903993 . FINDINGS Patients were enrolled between Aug 5 , 2013 , and March 31 , 2014 . 144 patients were r and omly allocated to the atezolizumab group , and 143 to the docetaxel group . 142 patients received at least one dose of atezolizumab and 135 received docetaxel . Overall survival in the intention-to-treat population was 12·6 months ( 95 % CI 9·7 - 16·4 ) for atezolizumab versus 9·7 months ( 8·6 - 12·0 ) for docetaxel ( hazard ratio [ HR ] 0·73 [ 95 % CI 0·53 - 0·99 ] ; p=0·04 ) . Increasing improvement in overall survival was associated with increasing PD-L1 expression ( TC3 or IC3 HR 0·49 [ 0·22 - 1·07 ; p=0·068 ] , TC2/3 or IC2/3 HR 0·54 [ 0·33 - 0·89 ; p=0·014 ] , TC1/2/3 or IC1/2/3 HR 0·59 [ 0·40 - 0·85 ; p=0·005 ] , TC0 and IC0 HR 1·04 [ 0·62 - 1·75 ; p=0·871 ] ) . In our exploratory analysis , patients with pre-existing immunity , defined by high T-effector-interferon-γ-associated gene expression , had improved overall survival with atezolizumab . 11 ( 8 % ) patients in the atezolizumab group discontinued because of adverse events versus 30 ( 22 % ) patients in the docetaxel group . 16 ( 11 % ) patients in the atezolizumab group versus 52 ( 39 % ) patients in the docetaxel group had treatment-related grade 3 - 4 adverse events , and one ( < 1 % ) patient in the atezolizumab group versus three ( 2 % ) patients in the docetaxel group died from a treatment-related adverse event . INTERPRETATION Atezolizumab significantly improved survival compared with docetaxel in patients with previously treated NSCLC . Improvement correlated with PD-L1 immunohistochemistry expression on tumour cells and tumour-infiltrating immune cells , suggesting that PD-L1 expression is predictive for atezolizumab benefit . Atezolizumab was well tolerated , with a safety profile distinct from chemotherapy . FUNDING F Hoffmann-La Roche/Genentech BACKGROUND Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma . The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study . METHODS We r and omly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab ( at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks ) or dacarbazine ( at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks ) . The primary end point was overall survival . RESULTS At 1 year , the overall rate of survival was 72.9 % ( 95 % confidence interval [ CI ] , 65.5 to 78.9 ) in the nivolumab group , as compared with 42.1 % ( 95 % CI , 33.0 to 50.9 ) in the dacarbazine group ( hazard ratio for death , 0.42 ; 99.79 % CI , 0.25 to 0.73 ; P<0.001 ) . The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group ( hazard ratio for death or progression of disease , 0.43 ; 95 % CI , 0.34 to 0.56 ; P<0.001 ) . The objective response rate was 40.0 % ( 95 % CI , 33.3 to 47.0 ) in the nivolumab group versus 13.9 % ( 95 % CI , 9.5 to 19.4 ) in the dacarbazine group ( odds ratio , 4.06 ; P<0.001 ) . The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups , including subgroups defined by status regarding the programmed death lig and 1 ( PD-L1 ) . Common adverse events associated with nivolumab included fatigue , pruritus , and nausea . Drug-related adverse events of grade 3 or 4 occurred in 11.7 % of the patients treated with nivolumab and 17.6 % of those treated with dacarbazine . CONCLUSIONS Nivolumab was associated with significant improvements in overall survival and progression-free survival , as compared with dacarbazine , among previously untreated patients who had metastatic melanoma without a BRAF mutation . ( Funded by Bristol-Myers Squibb ; CheckMate 066 Clinical Trials.gov number , NCT01721772 . ) 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 PURPOSE Programmed cell death 1 ( PD-1 ) is an inhibitory receptor expressed by activated T cells that downmodulates effector functions and limits the generation of immune memory . PD-1 blockade can mediate tumor regression in a substantial proportion of patients with melanoma , but it is not known whether this is associated with extended survival or maintenance of response after treatment is discontinued . PATIENTS AND METHODS Patients with advanced melanoma ( N = 107 ) enrolled between 2008 and 2012 received intravenous nivolumab in an outpatient setting every 2 weeks for up to 96 weeks and were observed for overall survival , long-term safety , and response duration after treatment discontinuation . RESULTS Median overall survival in nivolumab-treated patients ( 62 % with two to five prior systemic therapies ) was 16.8 months , and 1- and 2-year survival rates were 62 % and 43 % , respectively . Among 33 patients with objective tumor regressions ( 31 % ) , the Kaplan-Meier estimated median response duration was 2 years . Seventeen patients discontinued therapy for reasons other than disease progression , and 12 ( 71 % ) of 17 maintained responses off-therapy for at least 16 weeks ( range , 16 to 56 + weeks ) . Objective response and toxicity rates were similar to those reported previously ; in an extended analysis of all 306 patients treated on this trial ( including those with other cancer types ) , exposure-adjusted toxicity rates were not cumulative . CONCLUSION Overall survival following nivolumab treatment in patients with advanced treatment-refractory melanoma compares favorably with that in literature studies of similar patient population s. Responses were durable and persisted after drug discontinuation . Long-term safety was acceptable . Ongoing r and omized clinical trials will further assess the impact of nivolumab therapy on overall survival in patients with metastatic melanoma 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 . ) |
12,826 | 23,740,610 | Although behavioural interventions delivered by occupational therapists have been shown to reduce the rate of falls , we are unable to conclude if this is due to reduced activity restriction ( increased mobility ) or reduced activity ( lessening exposure to risk ) .
There are inconclusive and conflicting results from trials evaluating the effectiveness of behavioural and environmental interventions aim ed at improving quality of life . | BACKGROUND Impairment of vision is associated with a loss of function in activities of daily living .
Avoidance of physical activity and consequent reduced functional capacity is common in older people with visual impairment and an important risk factor for falls .
Indeed , the rate of falls and fractures is higher in older people with visual impairment than age-matched visually normal older people .
Depression and anxiety is common in older people with vision impairment and leads to further restriction of activity , reduced social contact and reduced quality of life .
Possible mechanisms to reduce activity restriction and therefore improve mobility and activity include environmental and behavioural interventions delivered by a number of health professionals , including occupational therapists .
OBJECTIVES The objective of this review was to assess the effectiveness of environmental and behavioural interventions in reducing activity limitation and improving quality of life amongst visually impaired older people .
SELECTION CRITERIA R and omised controlled trials ( RCTs ) and quasi-r and omised controlled trials ( Q- RCTs ) that compared environmental interventions , behavioural interventions or both , versus control ( placebo control or no intervention or usual care ) , and trials comparing different types of environmental or behavioural interventions , in older people ( aged 60 and over ) with irreversible visual impairment living independently or in residential setting s. To be eligible for inclusion the primary aim of studies must be reducing physical activity limitation and must include a measure of physical activity . | Background Orientation and mobility training ( O&M-training ) in using an identification cane , also called symbol cane , is provided to people with low vision to facilitate independent participation in the community . In The Netherl and s this training is mainly practice -based because a st and ardised and validly evaluated O&M-training in using the identification cane is lacking . Recently a st and ardised O&M-training in using the identification cane was developed . This training consists of two face-to-face sessions and one telephone session during which , in addition to usual care , the client 's needs regarding mobility are prioritised , and cognitive restructuring techniques , action planning and contracting are applied to facilitate the use of the cane . This paper presents the design of a r and omised controlled trial aim ed to evaluate this st and ardised O&M-training in using the identification cane in older adults with low vision . Methods / design A parallel group r and omised controlled trial was design ed to compare the st and ardised O&M-training with usual care , i.e. the O&M-training commonly provided by the mobility trainer . Community-dwelling older people who ask for support at a rehabilitation centre for people with visual impairment and who are likely to receive an O&M-training in using the identification cane are included in the trial ( N = 190 ) . The primary outcomes of the effect evaluation are ADL self care and visual functioning with respect to distance activities and mobility . Secondary outcomes include quality of life , feelings of anxiety , symptoms of depression , fear of falling , and falls history . Data for the effect evaluation are collected by means of telephone interviews at baseline , and at 5 and 17 weeks after the start of the O&M-training . In addition to an effect evaluation , a process evaluation to study the feasibility of the O&M-training is carried out . Discussion The screening procedure for eligible participants started in November 2007 and will continue until October 2009 . Preliminary findings regarding the evaluation are expected in the course of 2010 . If the st and ardised O&M-training is more effective than the current O&M-training or , in case of equal effectiveness , is considered more feasible , the training will be embedded in the Dutch national instruction for mobility trainers . Trial registration Clinical Trials.gov Background : Ageing with visual impairment is associated with a high degree of disability whereby age-related macular degeneration in particular causes dependence in activities of daily living ( ADL ) even at an early stage . Aims : To compare an activity-based , health-promotion programme with an individual programme , targeting the elderly with age-related macular degeneration concerning the effect on the development of dependence in ADL , general health , and self-reported health problems . Methods : A r and omized controlled study with a 28-month follow-up . A total of 229 persons were r and omized to the study and 131 ( 57 % ) were followed up ( individual intervention n=69 , health-promotion programme n=62 ) at 28-month . Results : The health-promotion group maintained their ADL level despite a significant decrease in visual acuity , while the individual intervention group increased its dependence in ADL . General health systematic ally dropped to a lower level in both groups , but participants from the health-promotion group reported fewer health problems . There were significantly fewer reports of tiredness and dizziness among the health-promotion participants . Conclusion : The health-promotion programme seems to have slowed down the disablement process among elderly with decreased vision by enabling them to maintain their ADL level and by reducing self-reported health problems for at least 28 months following intervention Background : Visual impairment and blindness are common in older people in Britain . It is important to know the causes of visual impairment to develop health service and research priorities . The authors aim ed to identify the causes of visual impairment in people aged 75 years and older in Britain . Methods : In the MRC Trial of the Assessment and Management of Older People in the Community , trial nurses tested visual acuity in everyone aged 75 years and older in 53 general practice s. For all visually impaired patients in 49 of the 53 medical practice s , data regarding the cause of vision loss were extracted from the general practice medical notes . Additional follow up question naires were also sent to the hospital ophthalmologist to confirm the cause of vision loss . Visual impairment was defined as a binocular acuity of less than 6/18 . Results : There were 1742 ( 12.5 % ) people visually impaired in the 49 participating practice s. Of these , 450 ( 26 % ) achieved a pinhole visual acuity in either eye of 6/18 or better . In these people , the principal reason for visual loss was considered to be refractive error . The cause of visual loss was available for 976 ( 76 % ) of the remaining 1292 visually impaired people identified . The main cause of visual loss was age related macular degeneration ( AMD ) ; 52.9 % ( 95 % confidence interval 49.2 to 56.5 ) of people had AMD as a main or contributory cause . This was followed by cataract ( 35.9 % ) , glaucoma ( 11.6 % ) , myopic degeneration ( 4.2 % ) , and diabetic eye disease ( 3.4 % ) . Conclusions : A substantial proportion of visual impairment in our sample of older people in Britain can be attributed to remediable causes — refractive error and cataract . There is considerable potential for visual rehabilitation in this age group . For the large proportion with macular degeneration , low vision services will be important Background / aims Ageing of the population will result in unprecedented numbers of older adults living with age-related vision loss ( ARVL ) . Self-management models improve health outcomes and reduce healthcare costs ; however , the principles have rarely been applied in low vision services . Methods A two-armed r and omised controlled trial of older adults ( n=77 ) with ARVL compared ‘ usual care ’ provided by a not-for-profit community agency with an extended model of care ( usual care+self-management group intervention ) . The primary outcome variable ( participation in life situations ) was measured using the Activity Card Sort . Secondary outcome measures examined general health and vision-specific domains . Results The intention-to-treat analysis demonstrated that the extended model produced significantly better participation in life situations at post-test when compared with the usual care only group . Gains were made regardless of whether participants were , or were not , depressed at baseline . The addition of the self-management group was also successful in significantly reducing depression , increasing physical and mental health , generalised and domain-specific self-efficacy , and adjustment to ARVL . With the exception of adjustment and mental health , differences were still apparent at 12 weeks ' follow-up . Conclusion Addition of self-management significantly improved general health and vision-specific rehabilitation outcomes for older adults with ARVL OBJECTIVE To evaluate the effectiveness of a low-vision rehabilitation program . METHODS A multicenter r and omized clinical trial was conducted from November 2004 to November 2006 with a 4-month follow-up . A total of 126 patients were included , 98 % of whom were white and male . The patients were referred from eye or low-vision clinics and blind rehabilitation centers with a visual acuity in the better-seeing eye worse than 20/100 and better than 20/500 and were eligible for Veterans Affairs ( VA ) services . Telephone interviews of patients were conducted in their homes before and after participation in an outpatient low-vision program at a VA medical care facility or a ( waiting list ) control group . The interviewer administering question naires by telephone was masked to patients ' assignments . Interventions included low-vision examination , counseling , and prescription and provision of low-vision devices and 6 weekly sessions provided by a low-vision therapist to teach use of assistive devices and adaptive strategies to perform daily living tasks independently . MAIN OUTCOME MEASURE Change in patients ' visual reading ability estimated from participant responses to the Veterans Affairs Low-Vision Visual Functioning Question naire ( LV VFQ-48 ) reading items completed at baseline compared with 4 months after enrollment for the treatment and control groups . The secondary outcomes were changes in other visual ability domains ( mobility , visual information processing , visual motor skills ) and overall visual ability from baseline to 4 months estimated from VA LV VFQ-48 difficulty ratings for subsets of items . RESULTS The treatment group demonstrated significant improvement in all aspects of visual function compared with the control group . The difference in mean changes was 2.43 logits ( 95 % confidence interval [ CI ] , 2.07 - 2.77 ; P < .001 ; effect size , 2.51 ) for visual reading ability ; 0.84 logit ( 95 % CI , 0.58 - 1.10 ; P < .001 ; effect size , 1.14 ) for mobility ; 1.38 logits ( 95 % CI , 1.15 - 1.62 ; P < .001 ; effect size , 2.03 ) for visual information processing ; 1.51 logits ( 95 % CI , 1.22 - 1.80 ; P < .001 ; effect size , 1.82 ) for visual motor skills ; and 1.63 logits ( 95 % CI , 1.40 - 1.86 ; P < .001 ; effect size , 2.51 ) for overall visual function . CONCLUSION The program effectively provided low-vision rehabilitation for patients with macular diseases . APPLICATIONS TO CLINICAL PRACTICE : At least 10 hours of low-vision therapy , including a home visit and assigned homework to encourage practice , is justified for patients with moderate and severe vision loss from macular diseases . Because the waiting-list control patients demonstrated a decline in functional ability , low-vision services should be offered as early as possible . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00223756 Background : In a r and omized controlled trial testing a home safety program design ed to prevent falls in older people with severe visual impairment , it was shown that the program , delivered by an experienced occupational therapist , significantly reduced the numbers of falls both at home and away from home . Objectives : To investigate whether the success of the home safety assessment and modification intervention in reducing falls result ed directly from modification of home hazards or from behavioral modifications , or both . Methods : Participants were 391 community living women and men aged 75 years and older with visual acuity 6/24 meters or worse ; 92 % ( 361 of 391 ) completed one year of follow up . Main outcome measures were type and number of hazards and risky behavior identified in the home and garden of those receiving the home safety program , compliance with home safety recommendations reported at six months , location of all falls for all study participants during the trial , and environmental hazards associated with each fall . Results : The numbers of falls at home related to an environmental hazard and those with no hazard involved were both reduced by the home safety program ( n = 100 participants ) compared with the group receiving social visits ( n = 96 ) ( incidence rate ratios = 0.40 ( 95 % confidence interval , 0.21 to 0.74 ) and 0.43 ( 0.21 to 0.90 ) , respectively ) . Conclusions : The overall reduction in falls by the home safety program must result from some mechanism in addition to the removal or modification of hazards or provision of new equipment Abstract Objective : To test the effectiveness of , and explore interactions between , three interventions to prevent falls among older people . Design : A r and omised controlled trial with a full factorial design . Setting : Urban community in Melbourne , Australia . Participants : 1090 aged 70 years and over and living at home . Most were Australian born and rated their health as good to excellent ; just over half lived alone . Interventions : Three interventions ( group based exercise , home hazard management , and vision improvement ) delivered to eight groups defined by the presence or absence of each intervention . Main outcome measure : Time to first fall ascertained by an 18 month falls calendar and analysed with survival analysis techniques . Changes to targeted risk factors were assessed by using measures of quadriceps strength , balance , vision , and number of hazards in the home . Results : The rate ratio for exercise was 0.82 ( 95 % confidence interval 0.70 to 0.97 , P=0.02 ) , and a significant effect ( P<0.05 ) was observed for the combinations of interventions that involved exercise . Balance measures improved significantly among the exercise group . Neither home hazard management nor treatment of poor vision showed a significant effect . The strongest effect was observed for all three interventions combined ( rate ratio 0.67 ( 0.51 to 0.88 , P=0.004 ) ) , producing an estimated 14.0 % reduction in the annual fall rate . The number of people needed to be treated to prevent one fall a year ranged from 32 for home hazard management to 7 for all three interventions combined . Conclusions : Group based exercise was the most potent single intervention tested , and the reduction in falls among this group seems to have been associated with improved balance . Falls were further reduced by the addition of home hazard management or reduced vision management , or both of these . Cost effectiveness is yet to be examined . These findings are most applicable to Australian born adults aged 70–84 years living at home who rate their health as good Purpose The purpose of this study was to investigate the effect of residential blind rehabilitation on patients ’ vision-targeted health-related quality of life ( HRQOL ) and general physical and mental function . Method The National Eye Institute 25-item Visual Function Question naire ( NEI VFQ ) plus appendix questions , the 12-item Short-Form Health Survey ( SF-12 ) , Hope Scale and Coopersmith self-esteem inventory were administered to 206 legally blind veterans prior to their entering a residential ( in-patient ) blind rehabilitation program and again to 185 and 176 of the original cohort at 2 and 6 months after completion of the rehabilitation program , respectively . Data on visual acuity , visual field extent , contrast sensitivity and scanning ability were also collected . The duration of the in-patient rehabilitation programs ranged from 11 to 109 days . Question naire scores were compared pre-rehabilitation and post-rehabilitation . Results Following rehabilitation there was a significant improvement in nine of 11 NEI VFQ subscales and in a composite score at both the 2- and 6-month post-rehabilitation intervals . Mental health ( SF-12 ) and self esteem also improved significantly although physical health ratings declined over the course of the study ( approximately 10 months ) . Conclusions Residential blind rehabilitation appears to improve patients ’ self-reported vision-targeted HRQOL , self-esteem and mental health aspects of generic HRQOL Aim : To compare the effectiveness of three models of low vision rehabilitation for people with age related macular degeneration ( AMD ) referred for low vision rehabilitation ( LVR ) : ( a ) an enhanced low vision rehabilitation model ( ELVR ) including supplementary home based low vision rehabilitation ; ( b ) conventional low vision rehabilitation ( CLVR ) based in a hospital clinic ; ( c ) CLVR with home visits that did not include rehabilitation ( CELVR ) , intended to act as a control for the additional contact time with ELVR . Method : A single centre parallel group r and omised controlled trial in participants ’ homes and the low vision clinic , Manchester Royal Eye Hospital . People referred for LVR with a primary diagnosis of AMD and visual acuity worse than 6/18 in both eyes and equal to or better than 1/60 in the better eye . The main outcome measures were vision specific quality of life ( QoL ) ( primary outcome , VCM1 ) and generic health related QoL ( SF-36 ) ; psychological adjustment to vision loss ; measured task performance ; restriction in everyday activities ; use of low vision aids ( LVAs ) . Results : 226 participants were recruited ( median age 82 years ) ; 194 completed the trial ( 86 % ) . Except for SF-36 physical and mental component summary scores , arms did not differ significantly for any of the outcomes . Differences for the VCM1 were ELVR v CLVR , 0.06 ( 95 % CI to 0.17 to 0.30 , p = 0.60 ) ; ELVR v CELVR , 0.12 ( 95 % CI to 0.11 to 0.34 , p = 0.31 ) ; CELVR v CLVR , –0.05 ( 95 % CI –0.29 to 0.18 , p = 0.64 ) . Differences for the SF-36 favoured CLVR compared to ELVR ( ELVR v CLVR : physical = –6.05 , 95 % CI –10.2 to –1.91 , p = 0.004 ; mental = –4.04 , 95 % CI –7.44 to –0.65 , p = 0.02 ) . At 12 months , 94 % of participants reported using at least one LVA . Conclusion : ELVR was no more effective than CLVR . Research ers should be wary of proposing new LVR interventions without preliminary evidence of effectiveness , given the manifest lack of effectiveness of the model of enhanced LVR evaluated in the trial The prevention of injury associated with falls in older people is a public health target in many countries around the world . Although there is good evidence that interventions such as multifactorial fall prevention and individually prescribed exercise are effective in reducing falls , the effect on serious injury rates is unclear . Historically , trials have not been adequately powered to detect injury endpoints , and variations in case definition across trials have hindered meta- analysis . It is possible that fall-prevention strategies have limited effect on falls that result in injuries or are ineffective in population s who are at a higher risk of injury . Further research is required to determine whether fall-prevention interventions can reduce serious injuries . Prevention of Falls Network Europe ( ProFaNE ) is a collaborative project to reduce the burden of fall injury in older people through excellence in research and promotion of best practice ( www.profane.eu.org ) . The European Commission funds the network , which links clinicians , members of the public , and research ers worldwide . The aims are to identify major gaps in knowledge in fall injury prevention and to facilitate the collaboration necessary for large-scale clinical research activity , including clinical trials , comparative research , and prospect i ve meta- analysis . Work is being undertaken in a 4-year program . As a first step , the development of a common set of outcome definitions and measures for future trials or meta- analysis was considered OBJECTIVES To evaluate the outcome of an intervention to reduce hazards in the home on the rate of falls in seniors . DESIGN R and omized controlled trial , with follow-up of subjects for 1 year . SETTING Community-based study in Perth , Western Australia . PARTICIPANTS People age 70 and older . INTERVENTION One thous and eight hundred seventy-nine subjects were recruited and r and omly allocated by household to the intervention and control groups in the ratio 1:2 . Because of early withdrawals , 1,737 subjects commenced the study . All members of both groups received a single home visit from a research nurse . Intervention subjects ( n = 570 ) were offered a home hazard assessment , information on hazard reduction , and the installation of safety devices , whereas control subjects ( n = 1,167 ) received no safety devices or information on home hazard reduction . MEASUREMENTS Both groups recorded falls on a daily calendar . Reported falls were confirmed by a semistructured telephone interview and were assigned to one of three overlapping categories : all falls , falls inside the home , and falls involving environmental hazards in the home . Analysis was by multivariate modelling of rate ratios and odds ratios for falls , corrected for household clustering , using Poisson regression and logistic regression with robust variance estimation . RESULTS Overall , 86 % of study subjects completed the 1 year of follow-up . The intervention was not associated with any significant reduction in falls or fall-related injuries . There was no significant reduction in the intervention group in the incidence rate of falls involving environmental hazards inside the home ( adjusted rate ratio , 1.11 ; 95 % CI = 0.82 - 1.50 ) , or the proportion of the intervention group who fell because of hazards inside the home ( adjusted odds ratio , 0.97 ; 95 % CI = 0.74 - 1.28 ) . No reduction was seen in the rate of all falls ( adjusted rate ratio , 1.02 ; 95 % CI = 0.83 - 1.27 ) or the rate of falls inside the home ( adjusted rate ratio , 1.17 ; 95 % CI = 0.85 - 1.60 ) . There was no significant reduction in the rate of injurious falls in intervention subjects ( adjusted rate ratio , 0.92 ; 95 % CI = 0.73 - 1.14 ) . CONCLUSIONS The intervention failed to achieve a reduction in the occurrence of falls . This was most likely because the intervention strategies had a limited effect on the number of hazards in the homes of intervention subjects . The study provides evidence that a one-time intervention program of education , hazard assessment , and home modification to reduce fall hazards in the homes of healthy older people is not an effective strategy for the prevention of falls in seniors PURPOSE : To test the hypothesis that vision rehabilitation using optometry , occupational therapy and social work services increases patients ' functional ability and to assess whether involving families in the intervention results in more successful outcomes . METHODS : We conducted an outcome study of 97 patients new to the Vision Rehabilitation Service . Subjects were between the ages of 19 and 91 years , with a median age of 76 . Their visual acuities were 20/100 or worse in the better eye , with 50 % of the subjects having acuities worse than 20/200 . Macular degeneration was the most prevalent diagnosis . Subjects were assigned to either an individually focused ( n=48 ) or a family focused ( n=49 ) intervention . The outcome measure was change in function , as assessed by speed and accuracy of performance ( objective measure ) and by the patients ' self-reports of difficulty and dependency in performing daily activities ( subjective measures ) . Data were collected before and after the intervention . RESULTS : Most patients had documented improvement after rehabilita-tion on both objective ( p=.0001 ) and subjective ( decreased dependency , p=.01 ) measures of function . The sample size did not provide adequate statistical power to show differences between family focused and individually focused interventions . CONCLUSIONS : This study documents significant improvement after vision rehabilitation for a predominately elderly population . Patients in both family and individually focused interventions improved comparably OBJECTIVES To determine the efficacy of vision and eye examinations , with subsequent treatment of vision problems , for preventing falls and fractures in frail older people . DESIGN R and omized , controlled trial . SETTING Community in Sydney , Australia . PARTICIPANTS Six hundred sixteen men and women aged 70 and older ( mean age 81 ) recruited mainly from people attending outpatient aged care services . INTERVENTIONS The intervention group received comprehensive vision and eye examinations conducted by a study optometrist . The optometrist arranged for new eyeglasses for 92 subjects and referred 24 for a home visit with an occupational therapist , 17 for glaucoma management , and 15 for cataract surgery . The control group received usual care . MEASUREMENTS Falls and fractures during 12 months of follow-up were ascertained according to self-report using a monthly postcard system . RESULTS Fifty-seven percent of subjects fell at least once during follow-up . Falls occurred more frequently in the group r and omized to receive the vision intervention ( 65 % fell at least once ; 758 falls in total ) than in the control group ( 50 % fell at least once ; 516 falls in total ) . The falls rate ratio using the negative binomial model was 1.57 ( 95 % confidence interval (CI)=1.20 - 2.05 , P=.001 ) . Fractures were also more frequent in the intervention group ( 31 fractures ) than the control group ( 18 fractures ; relative risk from proportional hazards model 1.74 , 95 % CI=0.97 - 3.11 , P=.06 ) . CONCLUSION In frail older people , comprehensive vision and eye assessment , with appropriate treatment , does not reduce , and may even increase , the risk of falls and fractures OBJECTIVE To examine the association of distant vision and physical function in the population of older adults . DESIGN Cross-sectional and cohort study . PARTICIPANTS 5143 older residents of three communities ( Established Population s for the Epidemiologic Studies of the Elderly ) who were interviewed in 1988 - 89 , including residents of two communities who were re-interviewed 15 months later ( n = 3133 , 97 % of those eligible ) . MEASURES Visual acuity screening , self-reported activities of daily living and mobility , and objective physical performance measures of balance , walking , and rising from a chair . RESULTS Limitations in mobility , activities of daily living , and physical performance were associated with worse visual function . In prospect i ve analyses controlling for potential confounders , participants with severe visual impairment had 3-fold higher odds of incident mobility and activity of daily living limitations than those with acuity of 20/40 or better ( P < 0.001 ) . In prospect i ve analyses investigating the relationship of vision with improvement in function , those with poor vision were about half as likely to improve as those with better acuity , but this relationship was only statistically significant for improvement in mobility limitations . CONCLUSIONS Distant visual function appears to play an important role in physical function , particularly for mobility . An intervention to improve vision in at-risk elders might preserve function and prevent disability ; this warrants further investigation Assistive devices ( AD ) have long played an important role in occupational therapy practice as a way of enabling activities of daily living ( ADL ) , but no studies to date have investigated the use of low vision AD among older persons with age-related macular degeneration ( AMD ) as well as devices for ADL performance and hearing . The purpose of this study was to describe AD users and to investigate the association of AD and ADL . A health promotion program versus an individual program was investigated within a r and omised design . The study was based on data from 131 participants , 28-months after intervention . Data on prescribed ADs were examined through medical records and registers . The participants in the health promotion program used low vision AD in combination with ADL devices to a higher degree , whereas participants in the individual program used just optical AD . Greater use of non-optical AD within the individual program and greater use of ADL devices within the health promotion program was weakly associated with higher level of ADL dependence . There was no significant association between the number of low vision AD and having a decreased , a maintained or improved level of dependence at 28 months Abstract Objectives To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision . Design R and omised controlled trial . Setting Dunedin and Auckl and , New Zeal and . Participants 391 women and men aged ≥(1 ) 75 with visual acuity of 6/24 or worse who were living in the community ; 92 % ( 361 of 391 ) completed one year of follow-up . Interventions Participants received a home safety assessment and modification programme delivered by an occupational therapist ( n = 100 ) , an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation ( n = 97 ) , both interventions ( n = 98 ) , or social visits ( n = 96 ) . Main outcome measures Numbers of falls and injuries result ing from falls , costs of implementing the home safety programme . Results Fewer falls occurred in the group r and omised to the home safety programme but not in the exercise programme ( incidence rate ratios 0.59 ( 95 % confidence interval 0.42 to 0.83 ) and 1.15 ( 0.82 to 1.61 ) , respectively ) . However , within the exercise programme , stricter adherence was associated with fewer falls ( P = 0.001 ) . A conservative analysis showed neither intervention was effective in reducing injuries from falls . Delivering the home safety programme cost $ NZ650 ( £ 234 , 344 euros , $ US432 ) ( at 2004 prices ) per fall prevented . Conclusion The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision . The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group , possibly due to low levels of adherence . Trial registration number IS RCT N15342873 OBJECTIVE The research ers sought to assess whether the widely used 1994 Cochrane Highly Sensitive Search Strategy ( HSSS ) for r and omized controlled trials ( RCTs ) in MEDLINE could be improved in terms of sensitivity , precision , or parsimony . METHODS A gold st and ard of 1,347 RCT records and a comparison group of 2,400 non-trials were r and omly selected from MEDLINE . Terms occurring in at least 1 % of RCT records were identified . Fifty percent of the RCT and comparison group records were r and omly selected , and the ability of the terms to discriminate RCTs from non-trial records was determined using logistic regression . The best performing combinations of terms were tested on the remaining records and in MEDLINE . RESULTS The best discriminating term was " Clinical Trial " ( Publication Type ) . In years where the Cochrane assessment of MEDLINE records had taken place , the strategies identified few additional unindexed records of trials . In years where Cochrane assessment has yet to take place , " R and omized Controlled Trial " ( Publication Type ) proved highly sensitive and precise . Adding six more search terms identified further , unindexed trials at reasonable levels of precision and with sensitivity almost equal to the Cochrane HSSS . CONCLUSIONS Most reports of RCTs in MEDLINE can now be identified easily using " R and omized Controlled Trial " ( Publication Type ) . More sensitive search es can be achieved by a brief strategy , the Centre for Review s and Dissemination/Cochrane Highly Sensitive Search Strategy ( 2005 revision ) PURPOSE To investigate the association between visual impairment and depression and anxiety in older people in Britain . DESIGN Population -based cross-sectional study . PARTICIPANTS Thirteen thous and nine hundred people aged 75 years and older in 49 family practice s in Britain . METHODS Vision was measured in 13 900 people aged 75 years and older in 49 family practice s taking part in a r and omized trial of health screening that included depression ( Geriatric Depression Scale [ GDS-15 ] ) and anxiety ( General Health Question naire [ GHQ-28 ] ) . Cause of visual impairment ( binocular acuity less than 6/18 ) was assessed from medical records . Analysis was by logistic regression ( odds ratio [ OR ] and 95 % confidence interval [ CI ] ) , taking account of potential health and social confounders . MAIN OUTCOME MEASURES Levels of depression and anxiety . RESULTS Visually impaired people had a higher prevalence of depression compared with people with good vision . Of visually impaired older people , 13.5 % were depressed ( GDS-15 score of 6 or more ) compared with 4.6 % of people with good vision ( age- and gender-adjusted OR , 2.69 ; 95 % CI , 2.03 - 3.56 ) . Controlling for potential confounding factors , particularly activities of daily living , markedly attenuated the association between visual impairment and depression ( OR , 1.26 ; 95 % CI , 0.94 - 1.70 ) . There was little evidence for any association between visual impairment and anxiety . On the GHQ-28 scale , 9.3 % of visually impaired people had 2 or more symptoms of anxiety compared with 7.4 % of people with good vision . CONCLUSIONS Although cause and effect can not be established in a cross-sectional study , it is plausible that people with visual impairment are more likely to experience problems with functioning , which in turn leads to depression OBJECTIVE The purpose of this r and omized , longitudinal study was to investigate the impact of a health education program on perceived security in the performance of daily occupations 4 months after the intervention period . METHOD Two groups of persons with age-related macular degeneration were compared : Those who had followed a newly developed health education program that was based on occupation and those who took part in a st and ard individual intervention program . RESULTS Significant differences in the level of perceived security between the groups were found for 13 of 28 occupations . Participants in the health education group maintained or improved their level of perceived security in 22 daily occupations , whereas those in the individual intervention group declined to a lower level in 17 daily occupations . CONCLUSION This study provides support for the effectiveness of the health education program to enhance security and hinder a progressive decline in perceived security in daily occupations |
12,827 | 28,516,472 | There is currently limited rigorous RCT evidence available regarding the clinical effectiveness of nasal decontamination in the prevention of SSI . | BACKGROUND Surgical site infection rates in the month following surgery vary from 1 % to 5 % .
Due to the large number of surgical procedures conducted annually , the costs of these surgical site infections ( SSIs ) can be considerable in financial and social terms .
Nasal decontamination using antibiotics or antiseptics is performed to reduce the risk of SSIs by preventing organisms from the nasal cavity being transferred to the skin where a surgical incision will be made .
Staphylococcus aureus ( S aureus ) colonises the nasal cavity and skin of carriers and can cause infection in open or unhealed surgical wounds .
S aureus is the leading nosocomial ( hospital-acquired ) pathogen in hospitals worldwide .
The potential effectiveness of nasal decontamination of S aureus is thought to be dependent on both the antibiotic/antiseptic used and the dose of application ; however , it is unclear whether nasal decontamination actually reduces postoperative wound infection in S aureus carriers .
OBJECTIVES To assess the effects of nasal decontamination on preventing surgical site infections ( SSIs ) in people who are S aureus carriers undergoing surgery . | IMPORTANCE Surgical site infections ( SSIs ) , commonly caused by methicillin-resistant Staphylococcus aureus ( MRSA ) , are associated with significant morbidity and mortality , specifically when hardware is implanted in the patient . Previously , we have demonstrated that a preoperative decontamination protocol using chlorhexidine gluconate washcloths and intranasal antiseptic ointment is effective in eradicating MRSA in the nose and on the skin of patients . OBJECTIVE To examine the effect of a decontamination protocol on SSIs in patients undergoing elective orthopedic surgery with hardware implantation . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve data base of patients undergoing elective orthopedic surgery with hardware implantation at the Michael E. DeBakey Veterans Affairs Medical Center in Houston , Texas , was analyzed from October 1 , 2012 , to December 31 , 2013 . Cohort groups before and after the intervention were compared . INTERVENTIONS Starting in May 2013 , during their preoperative visit , all of the patients watched an educational video about MRSA decontamination and were given chlorhexidine washcloths and oral rinse and nasal povidone-iodine solution to be used the night before and the morning of scheduled surgery . MAIN OUTCOMES AND MEASURES Thirty-day SSI rates were collected according to the definitions of the Centers for Disease Control and Prevention National Nosocomial Infections Surveillance . Data on demographics , comorbidities such as chronic obstructive pulmonary disease and coronary artery disease , tobacco use , alcohol use , and body mass index were also collected . Univariate analysis was performed between the 2 groups of patients . Multivariate analysis was used to identify independent predictors of SSI . RESULTS A total of 709 patients were analyzed ( 344 controls and 365 patients who were decolonized ) . Both groups were well matched with no significant differences in age , body mass index , sex , or comorbidities . All of the patients ( 100 % ) completed the MRSA decontamination protocol . The SSI rate in the intervention group was significantly lower ( 1.1 % ; 4 of 365 patients developed an SSI ) than the SSI rate in the control group ( 3.8 % ; 13 of 344 patients developed an SSI ) ( P = .02 ) . Multivariate logistic regression identified MRSA decontamination as an independent predictor of not developing an SSI ( adjusted odds ratio , 0.24 [ 95 % CI , 0.08 - 0.77 ] ; P = .02 ) . CONCLUSIONS AND RELEVANCE Our study demonstrates that preoperative MRSA decontamination with chlorhexidine washcloths and oral rinse and intranasal povidone-iodine decreased the SSI rate by more than 50 % among patients undergoing elective orthopedic surgery with hardware implantation . Universal decontamination using this low-cost protocol may be considered as an additional prevention strategy for SSIs in patients undergoing orthopedic surgery with hardware implantation and warrants further study BACKGROUND Nasal carriers of Staphylococcus aureus are at increased risk for health care-associated infections with this organism . Decolonization of nasal and extranasal sites on hospital admission may reduce this risk . METHODS In a r and omized , double-blind , placebo-controlled , multicenter trial , we assessed whether rapid identification of S. aureus nasal carriers by means of a real-time polymerase-chain-reaction ( PCR ) assay , followed by treatment with mupirocin nasal ointment and chlorhexidine soap , reduces the risk of hospital-associated S. aureus infection . RESULTS From October 2005 through June 2007 , a total of 6771 patients were screened on admission . A total of 1270 nasal swabs from 1251 patients were positive for S. aureus . We enrolled 917 of these patients in the intention-to-treat analysis , of whom 808 ( 88.1 % ) underwent a surgical procedure . All the S. aureus strains identified on PCR assay were susceptible to methicillin and mupirocin . The rate of S. aureus infection was 3.4 % ( 17 of 504 patients ) in the mupirocin-chlorhexidine group , as compared with 7.7 % ( 32 of 413 patients ) in the placebo group ( relative risk of infection , 0.42 ; 95 % confidence interval [ CI ] , 0.23 to 0.75 ) . The effect of mupirocin-chlorhexidine treatment was most pronounced for deep surgical-site infections ( relative risk , 0.21 ; 95 % CI , 0.07 to 0.62 ) . There was no significant difference in all-cause in-hospital mortality between the two groups . The time to the onset of nosocomial infection was shorter in the placebo group than in the mupirocin-chlorhexidine group ( P=0.005 ) . CONCLUSIONS The number of surgical-site S. aureus infections acquired in the hospital can be reduced by rapid screening and decolonizing of nasal carriers of S. aureus on admission . ( Current Controlled Trials number , IS RCT N56186788 . During two separate periods a total of 654 patients were included in a clinical study relating preoperative bacterial colonization to occurrence of postoperative wound infection in plastic surgery . During the second period one half of the patients were r and omized to receive prophylactic azithromycin . Bacteriological sample s were collected from the nasal vestibulum during both periods , and additionally from the surgical field during the second period . All patients had preoperative chlorhexidine bathing . The bacteriological findings were categorized as either normal flora or potentially pathogenic bacteria , and as either having no growth . Surgical wounds were divided into four contamination classes . Postoperative follow-up was 30 days , and assessment of wound infection was based on a grade d scale . We did not find any statistically significant relation between preoperative bacterial colonization and postoperative wound infection , regardless of place of sample collection , method of bacterial classification , class of contamination or use of prophylactic azithromycin INTRODUCTION Mupirocin applied to the anterior nares four times daily usually eliminates Staphylococcus aureus , including methicillin resistant , within 48 hours . Prophylactic intranasal mupirocin is safe , inexpensive and effective in reducing the overall sternal wound infection after open-heart surgery . This study was design ed to determine whether decreasing nasal bacterial colonization by applying mupirocin intra nasally decreases mediastinal , sternal , pulmonary and cutaneous infections after open-heart surgery . MATERIAL & METHODS After institutional approval and informed consent , 392 patients were included in a r and omized , prospect i ve study . Nasal cultures were taken for all patients before surgery . Patients were divided in two groups : Group I ( n = 190 ) receiving mupirocin in the anterior nares 4 times daily for 48 hours before surgery ; Group II ( n = 202 ) was the control group . Patients were followed for a month after surgery . All mediastinal , sternal , pulmonary and cutaneous infections were documented and treated with appropriate antibiotics . A Student test for quantitative data and a chi2 test for qualitative data were used for statistical analysis . p < or = 0.05 was considered significant . RESULTS The two groups had the same demographic characteristics and risk factors . Nasal carriage of Staphylococcus was 36.2 % in the two groups . Neither mediastinitis nor sternitis were noticed in any of the two groups . There was no statistical difference between the groups according to the frequency of the cutaneous infections ( Group I : 19/190 - Group II : 13/202 ) and pneumonia ( Group I : 7/190 - Group II : 13/202 ) . In patients who had nasal carriage of Staphylococcus , nasal decontamination has not shown a statistical difference of cutaneous infections of the lower limbs nor pneumonia . Although nasal decontamination reduced the incidence of sternal wound infection ( Gr I 0/190 - Gr II 4/202 ; p = 0.017 ) . Staphylococcus aureus , in the control group , induced more cutaneous infections ( 30.8 % vs 11.7 % ; p = 0.048 ) . CONCLUSION The usage of mupirocin for nasal decontamination before open-heart surgery reduces the incidence of the sternal wound infection , and does not seem to affect the frequency of cutaneous infections of the lower limbs nor pneumonia after this surgery CONTEXT Nosocomial infections are an important cause of morbidity and mortality after cardiac surgery . Decolonization of endogenous potential pathogenic microorganisms is important in the prevention of nosocomial infections . OBJECTIVE To determine the efficacy of perioperative decontamination of the nasopharynx and oropharynx with 0.12 % chlorhexidine gluconate for reduction of nosocomial infection after cardiac surgery . DESIGN , SETTING , AND PARTICIPANTS A prospect i ve , r and omized , double-blind , placebo-controlled clinical trial conducted at the Onze Lieve Vrouwe Gasthuis , Amsterdam , the Netherl and s , between August 1 , 2003 , and September 1 , 2005 . Of 991 patients older than 18 years undergoing elective cardiothoracic surgery during the study interval , 954 were eligible for analysis . INTERVENTION Oropharyngeal rinse and nasal ointment containing either chlorhexidine gluconate or placebo . MAIN OUTCOME MEASURES Incidence of nosocomial infection , in addition to the rate of Staphylococcus aureus nasal carriage and duration of hospital stay . RESULTS The incidence of nosocomial infection in the chlorhexidine gluconate group and placebo group was 19.8 % and 26.2 % , respectively ( absolute risk reduction [ ARR ] , 6.4 % ; 95 % confidence interval [ CI ] , 1.1%-11.7 % ; P = .002 ) . In particular , lower respiratory tract infections and deep surgical site infections were less common in the chlorhexidine gluconate group than in the placebo group ( ARR , 6.5 % ; 95 % CI , 2.3%-10.7 % ; P = .002 ; and 3.2 % ; 95 % CI , 0.9%-5.5 % ; P = .002 , respectively ) . For the prevention of 1 nosocomial infection , 16 patients needed to be treated with chlorhexidine gluconate . A significant reduction of 57.5 % in S aureus nasal carriage was found in the chlorhexidine gluconate group compared with a reduction of 18.1 % in the placebo group ( P<.001 ) . Total hospital stay for patients treated with chlorhexidine gluconate was 9.5 days compared with 10.3 days in the placebo group ( ARR , 0.8 days ; 95 % CI , 0.24 - 1.88 ; P = .04 ) . CONCLUSION Decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate appears to be an effective method to reduce nosocomial infection after cardiac surgery . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00272675 ABSTRACT The epidemiology and risks of Staphylococcus aureus carriage in continuous peritoneal dialysis ( CPD ) patients was studied in a single tertiary-care institution . On outpatient visits sample s for culture were routinely taken prospect ively from the CPD catheter exit site and the vestibulum nasi . Seventy-five patients with at least one culture positive for S. aureus in this period were included : 43 had genotypically identical S. aureus strains in over 80 % of the cultures and were classified as persistent carriers ; 32 were intermittent carriers . Persistent carriage was associated with a threefold higher risk for CPD-related infections and sixfold higher rates of vancomycin consumption compared to those for the intermittent carriers . No methicillin or vancomycin resistance was detected To study the prevalence of Staphylococcus aureus carriage and the impact of preoperatively treating carriers in prosthetic joint infection ( PJI ) , a prospect i ve r and omized trial was organized . From January 2010 to December 2012 , 1028 of 1305 total joint arthroplasties performed were screened , and selected carriers underwent preoperative decolonization . We observed a 22.2 % ( 228/1028 ) S aureus colonization rate and only 0.8 % methicillin-resistant S aureus . Prosthetic joint infection rate was higher , albeit not significantly , in S aureus carriers than among noncarriers-3.9 % ( 9/228 ) vs 2.0 % ( 16/800 ) . Treated and untreated carriers showed no significant differences-3.4 % ( 3/89 ) vs 4.3 % ( 6/139 ) . Most of the 14 S aureus PJI occurred in noncarriers suggesting a lack of causal relation between nasal and PJI S aureus . No clear benefit in screening/decolonizing carriers before total joint arthroplasty could be demonstrated The objective of this study was to determine whether use of mupirocin nasal ointment for perioperative eradication of Staphylococcus aureus nasal carriage is effective in preventing the development of surgical site infections ( SSIs ) . A r and omized , double-blind , placebo-controlled design was used . Either mupirocin or placebo nasal ointment was applied twice daily to 614 assessable patients from the day of admission to the hospital until the day of surgery . A total of 315 and 299 patients were r and omized to receive mupirocin and placebo , respectively . Eradication of nasal carriage was significantly more effective in the mupirocin group ( eradication rate , 83.5 % versus 27.8 % ) . In the mupirocin group , the rate of endogenous S. aureus infections was 5 times lower than in the placebo group ( 0.3 % and 1.7 % , respectively ; relative risk , 0.19 ; 95 % confidence interval , 0.02 - 1.62 ) . Mupirocin nasal ointment did not reduce the SSI rate ( by S. aureus ) or the duration of hospital stay Prospect i ve data on hip fracture from 3686 patients at a United Kingdom teaching hospital were analysed to investigate the risk factors , financial costs and outcomes associated with deep or superficial wound infections after hip fracture surgery . In 1.2 % ( 41 ) of patients a deep wound infection developed , and 1.1 % ( 39 ) had a superficial wound infection . A total of 57 of 80 infections ( 71.3 % ) were due to Staphylococcus aureus and 39 ( 48.8 % ) were due to MRSA . No statistically significant pre-operative risk factors were detected . Length of stay , cost of treatment and pre-discharge mortality all significantly increased with deep wound infection . The one-year mortality was 30 % , and this increased to 50 % in those who developed an infection ( p < 0.001 ) . A deep infection result ed in doubled operative costs , tripled investigation costs and quadrupled ward costs . MRSA infection increased costs , length of stay , and pre-discharge mortality compared with non-MRSA infection ChloraPrep ( 2 % chlorhexidine gluconate + 70 % isopropyl alcohol [ CHG + IPA ] in a 3.0-mL applicator ) is a recently approved antiseptic for preoperative skin preparation . This controlled open-label trial assessed the immediate and persistent antimicrobial efficacy and safety of CHG + IPA compared with 70 % IPA or a 2 % CHG aqueous solution alone . Each antiseptic significantly reduced abdominal and inguinal microbial counts from baseline at 10 minutes , 6 hours , and 24 hours ( P = .0001 ) . CHG + IPA provided significantly more persistent antimicrobial activity on abdominal sites than IPA ( P = .003 ) or CHG ( P = .028 ) at 24 hours . No skin irritations were reported for any of the three antiseptics OBJECTIVE To identify risk factors for surgical site infection ( SSI ) due to methicillin-resistant Staphylococcus aureus ( MRSA ) . DESIGN Prospect i ve case-control study . SETTING One tertiary and 6 community-based institutions in the southeastern United States . METHODS We compared patients with SSI due to MRSA with 2 control groups : matched uninfected surgical patients and patients with SSI due to methicillin-susceptible S. aureus ( MSSA ) . Multivariable logistic regression was used to determine variables independently associated with SSI due to MRSA , compared with each control group . RESULTS During the 5-year study period , 150 case patients with SSI due to MRSA were identified and compared with 231 matched uninfected control patients and 128 control patients with SSI due to MSSA . Two variables were independently associated with SSI due to MRSA in both multivariable regression models : need for assistance with 3 or more activities of daily living ( odds ratio [ OR ] compared with uninfected patients , 3.97 [ 95 % confidence interval { CI } , 2.18 - 7.25 ] ; OR compared with patients with SSI due to MSSA , 3.88 [ 95 % CI , 1.91 - 7.87 ] ) and prolonged duration of surgery ( OR compared with uninfected patients , 1.98 [ 95 % CI , 1.11 - 3.55 ] ; OR compared with patients with SSI due to MSSA , 2.33 [ 95 % CI , 1.17 - 4.62 ] ) . Lack of independence ( ie , poor functional status ) remained associated with an increased risk of SSI due to MRSA after stratifying by age . CONCLUSIONS Poor functional status was highly associated with SSI due to MRSA in adult surgical patients , regardless of age . A patient 's level of independence can be easily determined , and this information can be used preoperatively to target preventive interventions We determined risk factors associated with persistent carriage of methicillin-resistant Staphylococcus aureus ( MRSA ) among 102 patients enrolled in a double-blind , placebo-controlled trial of nasally administered mupirocin ointment . MRSA decolonization was unsuccessful in 77 ( 79 % ) of 98 patients who met the criteria for evaluation . By univariate analysis , 4 variables were found to be associated with persistent MRSA colonization ( P < .1 for all 4 ) : absence of mupirocin treatment , previous fluoroquinolone therapy , > or = 2 MRSA-positive body sites , and low-level mupirocin resistance . After multivariable Cox proportional hazards modeling , the presence of > or = 2 positive body sites ( adjusted hazard ratio [ AHR ] , 1.7 ; 95 % confidence interval [ CI ] , 1.0 - 2.9 ) and previous receipt of a fluoroquinolone ( AHR , 1.8 ; 95 % CI , 1.0 - 3.3 ) were independently associated with MRSA persistence , whereas nasal mupirocin tended to confer protection ( AHR , 0.6 ; 95 % CI , 0.4 - 1.0 ) . Low-level mupirocin resistance was observed in 9 genotypically different MRSA strains and was not independently associated with chronic MRSA carriage ( AHR , 1.5 ; 95 % CI , 0.9 - 2.5 ) . Our findings suggest that multisite MRSA carriage and previous receipt of a fluoroquinolone are independent risk factors for persistent MRSA colonization BACKGROUND Treatment of Staphylococcus aureus colonization before surgery reduces risk of surgical site infection ( SSI ) . The regimen of nasal mupirocin ointment and topical chlorhexidine gluconate is effective , but cost and patient compliance may be a barrier . Nasal povidone-iodine solution may provide an alternative to mupirocin . METHODS We conducted an investigator-initiated , open-label , r and omized trial comparing SSI after arthroplasty or spine fusion in patients receiving topical chlorhexidine wipes in combination with either twice daily application of nasal mupirocin ointment during the 5 days before surgery or 2 applications of povidone-iodine solution into each nostril within 2 hours of surgical incision . The primary study end point was deep SSI within the 3 months after surgery . RESULTS In the modified intent-to-treat analysis , a deep SSI developed after 14 of 855 surgical procedures in the mupirocin group and 6 of 842 surgical procedures in the povidone-iodine group ( P = .1 ) ; S. aureus deep SSI developed after 5 surgical procedures in the mupirocin group and 1 surgical procedure in the povidone-iodine group ( P = .2 ) . In the per protocol analysis , S. aureus deep SSI developed in 5 of 763 surgical procedures in the mupirocin group and 0 of 776 surgical procedures in the povidone-iodine group ( P = .03 ) . CONCLUSIONS Nasal povidone-iodine may be considered as an alternative to mupirocin in a multifaceted approach to reduce SSI . TRIAL REGISTRATION Clinical Trials.gov identifier : NCT01313182 Abstract Objective : Staphylococcus aureus ( S. aureus ) is a common pathogen in surgical site infections ( SSIs ) . Mupirocin ointment is an effective treatment for nasal carriers . We aim ed to investigate whether screening for nasal colonization of S. aureus and treating carriers prior to a cesarean section ( CS ) decreases the likelihood of SSI . Methods : This is a r and omized controlled trial . All participants underwent nasal culture prior to the CS . Nasal carriers of S. aureus were treated with Mupirocin ointment according to a st and ardized protocol . In the control group , nasal cultures were obtained immediately prior to surgery and carriers were not treated . Results : We recruited 568 patients . Demographic characteristics were comparable between the groups . S. aureus nasal colonization rates were 20.1 % and 14.9 % in the intervention and control groups , respectively ( p = 0.12 ) . S. aureus eradication rate with Mupirocin treatment was 88 % . SSI rates were similar in the intervention and control groups ( 13.1 % versus 12.1 % , respectively , p = 0.78 ) and in treated carriers , untreated carriers , and non-carriers ( 7.4 % versus 13.0 % versus 13.1 % , respectively , p = 0.69 ) . Previous CS was the only factor found to independently predict SSI ( OR 2.5 , CI 1.09–5.65 p = 0.029 ) . Conclusion : Pre-cesarean screening for nasal S. aureus carriage and decolonization does not appear to be an effective intervention in reducing SSI rates OBJECTIVES /HYPOTHESIS Surgical site infections ( SSIs ) are an important cause of morbidity and mortality after head and neck surgery . Our primary objective was to determine the efficacy of preoperative topical antimicrobial decolonization before head and neck surgery . STUDY DESIGN Prospect i ve , r and omized controlled trial . METHODS This study was conducted among 84 patients presenting for head and neck surgery requiring admission to an academic medical center . Preoperative cultures were performed to identify Staphylococcus aureus carriers . Patients were r and omized to preoperative topical antimicrobial decolonization with a 5-day regimen of chlorhexidine skin rinses and intranasal mupirocin coupled with st and ard perioperative systemic antimicrobial prophylaxis , versus st and ard prophylaxis alone . The main outcome was the incidence of SSIs . RESULTS Despite a trend suggesting a decrease in SSIs with perioperative topical antimicrobial decolonization ( 24 % vs. 10 % ) , there was no significant difference ( odds ratio , 0.34 ; 95 % confidence interval , 0.10 - 1.18 ; P = .079 ) . Patients with a higher American Society of Anesthesiologists score ( 3 vs. 1 ; P = .02 ) , with more operative blood loss ( P = .05 ) , and who required operative takeback ( P = .04 ) had a higher rate of SSIs ; there was a trend suggesting a higher rate of SSIs among patients undergoing clean-contaminated surgery compared to clean cases ( P = .08 ) and among those having received prior radiation ( P = .07 ) or chemotherapy ( P = .06 ) . CONCLUSIONS Preoperative antimicrobial decolonization did not significantly decrease the incidence of SSIs after head and neck surgery , but might be considered for high-risk groups despite the lack of conclusive evidence confirming efficacy . Risk factors for SSIs after head and neck surgery are identified for the first time in a prospect i ve study BACKGROUND Surgical site infections ( SSIs ) are complications of surgery that cause significant postoperative morbidity . SSI has been proposed as a potential indicator of the quality of care in the context of clinical governance and monitoring of the performance of NHS organisations against targets . OBJECTIVES We aim ed to address a number of objectives . Firstly , identify risk factors for SSI , criteria for stratifying surgical procedures and evidence about the importance of postdischarge surveillance ( PDS ) . Secondly , test the importance of risk factors for SSI in surveillance data bases and investigate interactions between risk factors . Thirdly , investigate and vali date different definitions of SSI . Lastly , develop models for making risk-adjusted comparisons between hospitals . DATA SOURCES A single hospital surveillance data base was used to address objectives 2 and 3 and the UK Surgical Site Infection Surveillance Service data base to address objective 4 . STUDY DESIGN There were four elements to the research : ( 1 ) systematic review s of risk factors for SSI ( two review ers assessed titles and abstract s of studies identified by the search strategy and the quality of studies was assessed using the Newcastle Ottawa Scale ) ; ( 2 ) assessment of agreement between four SSI definitions ; ( 3 ) validation of definitions of SSI , quantifying their ability to predict clinical outcomes ; and ( 4 ) development of operation-specific risk models for SSI , with hospitals fitted as r and om effects . RESULTS Review s of SSI risk factors other than established SSI risk indices identified other risk ; some were operation specific , but others applied to multiple operations . The factor most commonly identified was duration of preoperative hospital stay . The review of PDS for SSI confirmed the need for PDS if SSIs are to be compared meaningfully over time within an institution . There was wide variation in SSI rate ( SSI% ) using different definitions . Over twice as many wounds were classified as infected by one definition only as were classified as infected by both . Different SSI definitions also classified different wounds as being infected . The two most established SSI definitions had broadly similar ability to predict the chosen clinical outcomes . This finding is paradoxical given the poor agreement between definitions . Elements of each definition not common to both may be important in predicting clinical outcomes or outcomes may depend on only a subset of elements which are common to both . Risk factors fitted in multivariable models and their effects , including age and gender , varied by surgical procedure . Operative duration was an important risk factor for all operations , except for hip replacement . Wound class was included least often because some wound classes were not applicable to all operations or were combined because of small numbers . The American Association of Anesthesiologists class was a consistent risk factor for most operations . CONCLUSIONS The research literature does not allow surgery-specific or generic risk factors to be defined . SSI definitions varied between surveillance programmes and potentially between hospitals . Different definitions do not have good agreement , but the definitions have similar ability to predict outcomes influenced by SSI . Associations between components of the National Nosocomial Infections Surveillance risk index and odds of SSI varied for different surgical procedures . There was no evidence for effect modification by hospital . Estimates of SSI% should be disseminated within institutions to inform infection control . Estimates of SSI% across institutions or countries should be interpreted cautiously and should not be assumed to reflect quality of medical care . Future research should focus on developing an SSI definition that has satisfactory psychometric properties , that can be applied in everyday clinical setting s , includes PDS and is formulated to detect SSIs that are important to patients or health services . FUNDING The National Institute for Health Research Technology Assessment programme The CONSORT statement is used worldwide to improve the reporting of r and omised controlled trials . Kenneth Schulz and colleagues describe the latest version , CONSORT 2010 , which up date s the reporting guideline based on new method ological evidence and accumulating Summary Staphylococcus aureus is a common cause of postoperative wound infections , and nasal colonization by this organism is an important factor in the development of infections . Treatment with mupirocin can eradicate the organism in the short term , and prophylactic treatment of colonized patients may prevent postoperative S. aureus infections . A double-blind , r and omized , placebo-controlled trial was performed to determine whether nasal mupirocin administered pre-operatively to S. aureus carriers reduces the rates of sternal and leg wound infections after cardiac surgery . The study enrolled 263 patients with nasal S. aureus undergoing elective cardiac surgery at St. Michael 's Hospital , Toronto , Canada . Patients were assessed for infections in the immediate postoperative period and two months later . Two hundred and fifty-seven patients were included in the intention-to-treat analysis and re-analysed according to the actual treatment applied . Wound infections occurred in 17 ( 13.5 % ) mupirocin recipients and 11 ( 9.1 % ) placebo recipients ( P = 0.319 ) , with seven ( 5.4 % ) and six ( 4.7 % ) sternal infections , respectively . Two ( 1.6 % ) wound infections were acquired postoperatively in the mupirocin group , neither of which were caused by S. aureus . The placebo group had three ( 2.4 % ) nosocomial wound infections , with two ( 1.6 % ) S. aureus bacteraemias ( P = 0.243 ) . Among patients receiving mupirocin , 106 ( 81.5 % ) cleared S. aureus compared with 59 ( 46.5 % ) patients receiving placebo ( P < 0.0001 ) . There was no significant difference between intention-to-treat and actual treatment groups . Prophylactic intranasal mupirocin administered to S. aureus carriers did not reduce the rates of overall surgical site infections by S. aureus , and only showed a trend towards decreased incidence of nosocomial S. aureus infections BACKGROUND Patients with nasal carriage of Staphylococcus aureus have an increased risk of surgical-site infections caused by that organism . Treatment with mupirocin ointment can reduce the rate of nasal carriage and may prevent postoperative S. aureus infections . METHODS We conducted a r and omized , double-blind , placebo-controlled trial to determine whether intranasal treatment with mupirocin reduces the rate of S. aureus infections at surgical sites and prevents other nosocomial infections . RESULTS Of 4030 enrolled patients who underwent general , gynecologic , neurologic , or cardiothoracic surgery , 3864 were included in the intention-to-treat analysis . Overall , 2.3 percent of mupirocin recipients and 2.4 percent of placebo recipients had S. aureus infections at surgical sites . Of the 891 patients ( 23.1 percent of the 3864 who completed the study ) who had S. aureus in their anterior nares , 444 received mupirocin and 447 received placebo . Among the patients with nasal carriage of S. aureus , 4.0 percent of those who received mupirocin had nosocomial S. aureus infections , as compared with 7.7 percent of those who received placebo ( odds ratio for infection , 0.49 ; 95 percent confidence interval , 0.25 to 0.92 ; P=0.02 ) . CONCLUSIONS Prophylactic intranasal application of mupirocin did not significantly reduce the rate of S. aureus surgical-site infections overall , but it did significantly decrease the rate of all nosocomial S. aureus infections among the patients who were S. aureus carriers BACKGROUND Mupirocin nasal ointment may be prescribed for decolonization prior to surgical procedures , especially for carriers of methicillin-resistant Staphylococcus aureus ( MRSA ) . The approved regimen for decolonization of S. aureus from the anterior nares is twice daily for 5 d ( 10 doses ) . We performed a two-center , r and omized , open-label study to compare the utility of six and 10 doses for decolonization of S. aureus . METHODS Patients expecting to undergo surgery were screened for S. aureus nasal carriage approximately three weeks prior to the procedure . Those found to be positive were offered enrollment in the study . In the first arm ( n=41 ) , patients were r and omized to receive 2 , 3 , or 5 d ( six or 10 doses ) of treatment prior to their operation . Their anterior nares were swabbed for culture and S. aureus polymerase chain reaction ( PCR ) during the decolonization therapy period as well as for four weeks after surgery . In the second arm ( n=60 ) , all patients were given 5 d ( 10 doses ) of nasal mupirocin treatment , and the patient 's anterior nares were swabbed for culture and S. aureus PCR for four weeks after surgery . Data from six of the patients were excluded from analysis because of failure to su bmi t swabs after operation . All S. aureus isolates were tested for susceptibility to mupirocin and the presence of the mecA gene to detect MRSA . RESULTS In Arm 1 , 16 patients received 10 doses of mupirocin , 18 received six doses ( twice daily for 3 d ) , and 7 received six doses ( thrice daily for 2 d ) . In the second arm , all patients received 10 doses of mupirocin ( twice a day for 5 d ) . Overall , 89.5 % patients who received 10 doses of mupirocin remained decolonized for at least four weeks after surgery versus 68.0 % of patients who received six doses ( p=0.016 ) . There was no difference between arms 1 and 2 for those given mupirocin twice daily for 5 d. CONCLUSION The ten-dose regimen is superior to any six-dose regimen for de-colonizing S. aureus from the anterior nares of patients and for maintaining the decolonized state for at least four weeks after therapy Two topical MRSA eradication regimes were compared in hospital patients : a st and ard treatment included mupirocin 2 % nasal ointment , chlorhexidine gluconate 4 % soap , silver sulfadiazine 1 % cream versus a tea tree oil regimen , which included tea tree 10 % cream , tea tree 5 % body wash , both given for five days . One hundred and fourteen patients received st and ard treatment and 56 ( 49 % ) were cleared of MRSA carriage . One hundred and ten received tea tree oil regimen and 46 ( 41 % ) were cleared . There was no significant difference between treatment regimens ( Fisher 's exact test ; P = 0.0286 ) . Mupirocin was significantly more effective at clearing nasal carriage ( 78 % ) than tea tree cream ( 47 % ; P = 0.0001 ) but tea tree treatment was more effective than chlorhexidine or silver sulfadiazine at clearing superficial skin sites and skin lesions . The tea tree preparations were effective , safe and well tolerated and could be considered in regimens for eradication of MRSA carriage |
12,828 | 26,867,879 | Concomitant administration of pilocarpine during radiation could increase the unstimulated salivary flow rate in a period of 3 to 6 months after treatment , and also reduce the clinician-rated xerostomia grade .
Patient-reported xerostomia was not significantly impacted by pilocarpine in the initial 3 months but was superior at 6 months .
No significant difference of stimulated salivary flow rate could be confirmed between the 2 arms .
Adverse effects of pilocarpine were mild and tolerable .
CONCLUSIONS The concomitant administration of pilocarpine during radiation increases unstimulated salivary flow rate and reduces clinician-rated xerostomia grade after radiation .
It also relieves patients ' xerostomia at 6 months and possibly at 12 months .
However , pilocarpine has no effect on stimulated salivary flow rate | PURPOSE To evaluate the efficacy of concomitant administration of pilocarpine on radiation-induced xerostomia in patients with head and neck cancers . | PURPOSE To investigate the impact of xerostomia on overall quality of life ( QoL ) outcome and related dimensions among head and neck cancer patients treated with primary radiotherapy . METHODS AND MATERIAL S A total of 288 patients with Stage I-IV disease without distant metastases were included . Late xerostomia according to the Radiation Therapy Oncology Group ( RTOG-xerostomia ) and QoL ( European Organization for Research and Treatment of Cancer QLC-C30 ) were assessed at baseline and every 6th month from 6 months to 24 months after radiotherapy . RESULTS A significant association was found between RTOG-xerostomia and overall QoL outcome ( effect size [ ES ] 0.07 , p < 0.001 ) . A significant relationship with global QoL , all functioning scales , and fatigue and insomnia was observed . A significant interaction term was present between RTOG-xerostomia and gender and between RTOG-xerostomia and age . In terms of gender , RTOG-xerostomia had a larger impact on overall QoL outcome in women ( ES 0.13 for women vs. 0.07 for men ) . Furthermore , in women ES on individual scales were larger , and a marked worsening was observed with increasing RTOG-xerostomia . No different ES according to age was seen ( ES 0.10 for 18 - 65 years vs. 0.08 for > 65 years ) . An analysis of the impact of RTOG-xerostomia on overall QoL outcome over time showed an increase from 0.09 at 6 months to 0.22 at 24 months . With elapsing time , a worsening was found for these individual scales with increasing RTOG-xerostomia . CONCLUSIONS The results of this prospect i ve study are the first to show a significant impact of radiation-induced xerostomia on QoL. Although the incidence of Grade > or = 2 RTOG-xerostomia decreases with time , its impact on QoL increases . This finding emphasizes the importance of prevention of xerostomia PURPOSE To evaluate chronic xerostomia and tumor control 18 and 24 months after initial treatment with amifostine in a r and omized controlled trial of patients with head- and -neck cancer ; at 12 months after radiotherapy ( RT ) , amifostine had been shown to reduce xerostomia without changing tumor control . METHODS AND MATERIAL S Adults with head- and -neck cancer who underwent once-daily RT for 5 - 7 weeks ( total dose , 50 - 70 Gy ) received either open-label amifostine ( 200 mg/m2 i.v . ) 15 - 30 min before each fraction of radiation ( n = 150 ) or RT alone ( control ; n = 153 ) . RESULTS Amifostine administration was associated with a reduced incidence of Grade > or = 2 xerostomia over 2 years of follow-up ( p = 0.002 ) , an increase in the proportion of patients with meaningful ( > 0.1 g ) unstimulated saliva production at 24 months ( p = 0.011 ) , and reduced mouth dryness scores on a patient benefit question naire at 24 months ( p < 0.001 ) . Locoregional control rate , progression-free survival , and overall survival were not significantly different between the amifostine group and the control group . CONCLUSIONS Amifostine administration during head- and -neck RT reduces the severity and duration of xerostomia 2 years after treatment and does not seem to compromise locoregional control rates , progression-free survival , or overall survival Background . Salivary gl and hypofunction commonly develops during radiation therapy to the head and neck region . This study evaluated whether the sialogogue pilocarpine given during radiation therapy may reduce the severity of xerostomia and salivary dysfunction PURPOSE To assess long-term xerostomia in patients receiving parotid-sparing radiation therapy ( RT ) for head- and -neck cancer , and to find the patient and therapy-related factors that affect its severity . PATIENTS AND METHODS From March 1994 through January 2000 , 84 patients received comprehensive bilateral neck RT using conformal and multisegmental intensity-modulated RT ( IMRT ) aim ing to spare the major salivary gl and s. Before RT and periodically through 2 years after the completion of RT , salivary flow rates from each of the major salivary gl and s were selectively measured . At the same time intervals , each patient completed an 8-item self-reported xerostomia-specific question naire ( XQ ) . To gain a relative measure of the effect of RT on the minor salivary gl and s , whose output could not be measured , the surfaces of the oral cavity ( extending to include the surface of the base of tongue ) were outlined in the planning CT scans . The mean doses to the new organ ( " oral cavity " ) were recorded . Forty-eight patients receiving unilateral neck RT were similarly studied and served as a benchmark for comparison . Factors predicting the XQ scores were analyzed using a r and om-effects model . RESULTS The XQ was found to be reliable and valid in measuring patient-reported xerostomia . The spared salivary gl and s which had received moderate doses in the bilateral RT group recovered to their baseline salivary flow rates during the second year after RT , and the spared gl and s in the unilateral RT group , which had received very low doses , demonstrated increased salivary production beyond their pre-RT levels . The increase in the salivary flow rates during the second year after RT paralleled an improvement in xerostomia in both patient groups . The improvement in xerostomia was faster in the unilateral compared with the bilateral RT group , but the difference narrowed at 2 years . The major salivary gl and flow rates had only a weak correlation with the xerostomia scores . Factors found to be independently associated with the xerostomia scores were the pre-RT baseline scores , the time since RT , and the mean doses to the major salivary gl and s ( notably to the subm and ibular gl and s ) and to the oral cavity . CONCLUSION An improvement over time in xerostomia , occurring in t and em with rising salivary production from the spared major salivary gl and s , suggests a long-term clinical benefit from their sparing . The oral cavity mean dose , representing RT effect on the minor salivary gl and s , was found to be a significant , independent predictor of xerostomia . Thus , in addition to the major salivary gl and s , sparing the uninvolved oral cavity should be considered as a planning objective to further reduce xerostomia BACKGROUND This prospect i ve r and omized study was undertaken to assess the effectiveness of oral pilocarpine chloratum ( Salagen ) during and after radiotherapy . PATIENTS AND METHODS Between October 1999 and December 2003 , 66 patients received 60 Gy of irradiation to their head and neck cancer . Half of the patients received 5 mg oral pilocarpine 3 times a day from the beginning of radiotherapy over a period of 12 weeks . The control group received similar doses of pilocarpine only in the second 6 weeks following irradiation . Patient saliva secretion was recorded , and a visual analog scale measuring overall and daily xerostomia , difficulty in sleeping , speaking , eating and wearing dentures was employed . RESULTS Pilocarpine , given concomitantly with radiotherapy , statistically improved the salivary flow and induced better patient comfort by the end of radiotherapy . Patient comfort and symptoms related to xerostomia greatly decreased compared to patients receiving pilocarpine after irradiation in the second 6-week period of therapy . The patients ' quality of life , saliva production and symptoms related to xerostomia showed significant progress by the end of the 12 weeks . CONCLUSION The results suggest that stimulated salivary gl and s suffer less decrease in saliva production during radiotherapy . The stimulated saliva flow reduced the side-effects of irradiation PURPOSE To investigate the effect of concomitant administration of pilocarpine during radiotherapy for head- and -neck squamous cell carcinoma ( HNSCC ) on postradiotherapy xerostomia . METHODS AND MATERIAL S A prospect i ve , double blind , placebo-controlled r and omized trial including 170 patients with HNSCC was executed to study the protective effect of pilocarpine on radiotherapy-induced parotid gl and dysfunction . The primary objective endpoint was parotid flow rate complication probability ( PFCP ) scored 6 weeks , 6 months , and 12 months after radiotherapy . Secondary endpoints included Late Effects of Normal Tissue/Somatic Objective Management Analytic scale ( LENT SOMA ) and patient-rated xerostomia scores . For all parotid gl and s , dose-volume histograms were assessed because the dose distribution in the parotid gl and s is considered the most important prognostic factor with regard to radiation-induced salivary dysfunction . RESULTS Although no significant differences in PFCP were found for the two treatments arms , a significant ( p = 0.03 ) reduced loss of parotid flow 1 year after radiotherapy was observed in those patients who received pilocarpine and a mean parotid dose above 40 Gy . The LENT SOMA and patient-rated xerostomia scores showed similar trends toward less dryness-related complaints for the pilocarpine group . CONCLUSIONS Concomitant administration of pilocarpine during radiotherapy did not improve the PFCP or LENT SOMA and patient-rated xerostomia scores . In a subgroup of patients with a mean dose above 40 Gy , pilocarpine administration result ed in sparing of parotid gl and function . Therefore , pilocarpine could be provided to patients in whom sufficient sparing of the parotid is not achievable PURPOSE To test the hypothesis that the use of oral pilocarpine during and after radiotherapy ( RT ) for head- and -neck cancer would reduce the symptoms of post-RT xerostomia . METHODS AND MATERIAL S One hundred thirty patients were r and omized in a double-blind method to receive either pilocarpine ( 5-mg tablets ) or placebo three times daily starting on Day 1 of RT and continuing for 1 month after treatment . The eligibility criteria included a planned dose of > 50 Gy as radical or postoperative RT for head- and -neck cancer , with at least 50 % of both parotid gl and s included in the treatment fields . The primary outcome measure was the severity of xerostomia as assessed by a patient-completed linear analog scale 3 months after RT . Secondary outcome measures included quality of life during therapy ( as assessed by the McMaster University Head- and -Neck Question naire ) and severity of mucositis during RT ( as assessed using Radiation Therapy Oncology Group scales ) . RESULTS No difference was observed between the pilocarpine-treated patients and the placebo group in the severity of xerostomia score as assessed by linear analog scale at baseline and 1 , 3 , and 6 months after treatment ( repeated measures analysis , p = 0.92 ) . No difference was apparent in the severity of mucositis during RT ; 56.3 % of patients receiving pilocarpine had Grade III/IV mucositis compared with 50.8 % treated with placebo . No difference in quality of life was noted between the treatment groups during or after RT . The question naire score at 3 months after RT was 5.0 ( SD 1.0 ) . in the pilocarpine group and 4.9 ( SD 0.9 ) in the placebo group . CONCLUSION We were unable to detect a beneficial effect of pilocarpine on RT-induced xerostomia when administered during RT for head- and -neck cancer Radiation therapy is an important curative modality in the treatment of patients with head and neck cancer . However , radiation-induced changes in the oral cavity , such as xerostomia and mucositis , are among the most debilitating treatment sequelae experienced by patients undergoing radiation therapy , and attempts at ameliorating these side effects have been poor at best . Pilocarpine has been approved for post-radiation xerostomia , and the effect of its use during radiation therapy on salivary flow , xerostomia , mucositis , and quality of life ( QOL ) was assessed in a phase III study conducted by the Radiation Therapy Oncology Group ( RTOG 97 - 09 ) . In total , 245 evaluable patients were r and omized to pilocarpine or placebo . Selected patients were required to have > or = 50 % of the volume of the major salivary gl and s receive > or = 50Gy ; to agree to provide stimulated and unstimulated sample s of saliva ( measured in g ) before treatment , at the end of treatment , and 3 and 6 months after completion of radiation therapy ; and to complete the University of Washington Head and Neck Symptom Scale . Following the completion of radiation therapy , the average unstimulated salivary flow was statistically greater in the pilocarpine group , whereas no difference was noted following parotid stimulation . There was no effect on the amelioration of mucositis . The results of the QOL scales did not reveal any significant difference between the pilocarpine and placebo groups with regard to xerostomia and mucositis . The significant difference in unstimulated salivary flow supports the concomitant use of oral pilocarpine to decrease radiation-associated xerostomia . However , the absent correlation between improved salivary flow and QOL scores is of some concern ( though not a new finding ) and may be related to the existence of comorbidities and the lack of effect on mucositis BACKGROUND Xerostomia is one of the disturbing side-effects of radiotherapy to the head and neck region . Pilocarpine has been approved for the treatment of this condition in the chronic phase , but its use concurrent with radiation could also be beneficial for prevention or reduction of the subsequent radiation-induced xerostomia . We undertook to test this hypothesis in a clinical trial . METHODS At the start of radiotherapy , r and omization was performed to either pilocarpine 5 mg three times daily or placebo in a double-blind setting . The drug was started with irradiation and continued until 3 months after the end of radiotherapy . Xerostomia was evaluated 6 months after the end of radiation by a subjective visual analog scale question naire . Also the objective grade of xerostomia was recorded by two separate observers . RESULTS A total number of 60 patients were r and omized into the trial , but unfortunately only 39 patients were finally evaluated for xerostomia , 18 in the pilocarpine and 21 in the placebo group . Mean age was 42 years , and mean parotid dose was 58 Gy . Mean subjective xerostomia was 40.3 mm in the pilocarpine group and 57 mm in the placebo group ( P = 0.02 ) . Also mean objective xerostomia grade was 2.2 in the pilocarpine group and 2.6 in the placebo group ( P = 0.01 ) . Subjective and objective xerostomia results were positively correlated ( P = 0.01 ) . Age and the parotid dose did not have a significant effect on xerostomia . CONCLUSIONS Compared to placebo , pilocarpine used with radiotherapy could lead to a significant diminishment of subsequent radiation-induced xerostomia PURPOSE To examine the Late Effects Normal Tissue Task Force (LENT)-Subjective , Objective , Management , Analytic ( SOMA ) scales prospect ively in carcinoma of the cervix treated curatively with radiotherapy ( RT ) using interviews and postal question naires and to test the sensitivity of the scales in assessing the radiation effects . METHODS AND MATERIAL S A consecutive series of 100 patients completed question naires to score the subjective part of the published LENT-SOMA scales . Assessment s were made before RT and at approximately 21 , 70 , 200 , 400 , 600 , and 800 days after the start of treatment . The acceptability and feasibility of using the scales was examined using compliance in completion of the question naires . The scales were vali date d by evaluating the concordance of data obtained by two independent scorers and by examining the ability of the scales to measure radiation-related symptoms . RESULTS Question naires were completed for 89 patients before RT . The level of noncompliance was 11 % . The concordance between scores when two people completed the question naires independently was excellent . Subjective subsite scores were highest 21 days after treatment but generally fell by 70 days . The average baseline overall LENT-SOMA subjective scores increased with advancing stage ( p = 0.008 ) and were higher for patients treated with RT alone ( p = 0.044 ) . CONCLUSION In cervical carcinoma , the LENT-SOMA scales were acceptable and feasible to administer in the clinic and appropriate in the measurement of early subjective morbidity from RT OBJECTIVE The efficacy of pilocarpine given during radiotherapy for head-neck cancer to reduce xerostomia was assessed . STUDY DESIGN 58 patients receiving 5000 cGy radiotherapy ( RT ) involving salivary gl and s bilaterally were selected at the Jewish General Hospital , Montreal , Canada . Patients were r and omly assigned to pilocarpine ( 5 mg , PILO , n=29 ) or placebo group ( PLA , n=29 ) . These drugs were taken 5 times daily during radiotherapy ( first study phase ) and 4 times daily for 5 weeks thereafter ( second study phase ) . Saliva was collected and estimated for not stimulated and stimulated patients using the SAXON method . RESULTS At the conclusion of the first phase , PILO patients reported a better global quality of life ( P=.02 ) and less oral discomfort ( P=.001 ) when compared to PLA . No significant difference was noted in the level of saliva , xerostomia , and other symptoms between patients in PILO and PLA . At the end of the second phase , a difference between groups was observed only for xerostomia and mucosal pain ; both were significantly higher in PILO when compared to PLA ( P < .05 ) . CONCLUSION Pilocarpine 5 mg given 5 times daily did not appear to improve the production of saliva and global quality of life assessment s , nor to decrease the symptoms of xerostomia 5 weeks after completion of RT in patients who were taking pilocarpine post-RT . There was a slight improvement in the quality of life and a decrease in the level of discomfort noted only after the first study phase . The limitations of this study are discussed Patients with head and neck cancers can develop salivary hypofunction after radiotherapy . The use of pilocarpine during radiotherapy treatment has been shown to be an effective treatment , although its usefulness is being discussed . The aim of this study was : ( 1 ) to determine the value of a semiquantitative scintigraphy method for measuring the uptake and excretory salivary function of patients with head and neck irradiated tumours ; and ( 2 ) to study the usefulness of pilocarpine as a salivary gl and protector during radiotherapy . We prospect ively studied 49 patients ( mean age 61 years , range 29 - 87 years ) with head and neck cancer in need of radiotherapy . Patients were divided into two groups consecutively : group P ( 26 patients ) received 5 mg of pilocarpine three times per day starting the day before radiation therapy , and group NP ( 23 patients ) received radiotherapy without pilocarpine and were used as the control group . Salivary gl and scintigraphy and a visual analogue scale ( VAS ) of mouth dryness were obtained from each patient before radiotherapy and during the first year after treatment . The most frequent finding after radiotherapy was a quick impairment in parotid and submaxillary excretion ( P<0.001 ) . There were no statistical differences comparing the pilocarpine group against the non-pilocarpine group . Parotid and submaxillary uptake significantly decreased after radiotherapy in both groups ( P<0.001 ) . However , a tendency to recover within the pilocarpine group was observed in both the parotids and the submaxillary gl and s at 12 months . No differences were found comparing the VAS results in both groups . Strikingly , VAS data did not correlate with salivary gl and dysfunction observed by means of scintigraphy . In conclusion , salivary scintigraphy is a useful technique to evaluate objective ly the salivary gl and function of patients with head and neck irradiated tumours as well as to test the response to pilocarpine . However , despite better results on the salivary uptake at 12 months , pilocarpine did not significantly improve salivary gl and function Many controlled trials rely on subjective measures of symptoms or quality of life as primary outcomes . The relative merits of different response options for these measures is an important , but largely unexplored , issue . Therefore , we compared the responsiveness of seven-point Likert vs visual analogue scales ( VAS ) in a question naire measuring quality of life in chronic lung disease . The VAS and seven-point scale versions of the question naire were administered to 28 patients before and after completing an inpatient respiratory rehabilitation program of known benefit . For all four dimensions of the question naire ( dyspnea , fatigue , emotional function , and mastery ) the VAS showed a larger improvement than the seven-point scale when both were st and ardized on a scale of 0 - 10 . However , in each case the variability of the improvement was greater using the VAS . The difference in improvement between the two scales was not statistically significant . We conclude that the two methods of presenting response options show comparable responsiveness . The ease of administration and interpretation of the seven-point scale recommend its use in clinical trials PURPOSE To retrospectively compare subjective postirradiation xerostomia scores of patients who received concomitant oral pilocarpine during radiotherapy for head and neck cancer and 3 months thereafter with those of similar cohorts who did not receive pilocarpine . METHODS AND MATERIAL S Subjective xerostomia was assessed using a visual analog scale xerostomia question naire that measured oral dryness , oral comfort , difficulty with sleep , speech , and eating . The concomitant pilocarpine group had both parotid gl and s in the initial field treated to at least 45 Gy and received 5 mg pilocarpine hydrochloride four times per day ( q.i.d . ) beginning on the first day of radiotherapy and continuing for 3 months after completion of radiation . The control cohort had also received at least 45 Gy to both parotid gl and s and had not received pilocarpine at the time of evaluation . Scores on the visual analog scale were averaged and compared using the Student 's t-test . RESULTS Seventeen patients who received concomitant pilocarpine during head and neck irradiation and 18 patients who had not been treated with pilocarpine were available for follow-up . The mean intervals between completion of radiation and evaluation of xerostomia were 17 months and 16 months , respectively . Only one of the pilocarpine-treated patients was still taking pilocarpine at the time of evaluation . For each of the individual components of xerostomia scored on the visual analog scale , as well as the composite of all components , the group that had received oral pilocarpine during radiation had significantly less xerostomia ( p < 0.01 for each ) . CONCLUSIONS The use of 5 mg oral pilocarpine q.i.d . during radiotherapy for head and neck cancer and 3 months thereafter was associated with significantly less subjective xerostomia than that reported by a similar cohort of patients who had not received pilocarpine . The continued use of pilocarpine does not appear to be necessary to maintain this benefit in most patients The therapeutic use of ionizing radiations is predicated on sparing normal tissue effects while attempting to achieve lethal effects on tumor cells . From quite early in the history of radiation therapy , it was apparent that there were striking differences in effects in the panoply of normal tissues . Although there was early appreciation of some late effects in normal tissues , often not predicted by acute reactions , only in recent years has there been full documentation of the slow and progressive increase in severity of late damage . Pathophysiological mechanisms of acute and late radiation effects are better understood today ( 2 ) , but interactions of other modalities with radiation therapy require constant monitoring to recognize and mitigate untoward sequelae . The work of Stone ( 3 ) is a classic example of unanticipated late effects , which result ed from irradiation with ‘ fast neutrons . Acute reactions were moderate and tolerable , but the late sequelae were so marked that there was little interest in pursuing therapy with fast neutrons for nearly three decades . The Late Morbidity Scoring Criteria were developed as a joint effort between physicians with renewed interests in fast neutron therapy and Radiation Therapy Oncology Group ( RTOG ) staff . In the late 1970s the Neutron/Particle Committee was one of several modality committees of the RTOG . Recognizing the results of Stone , this committee , led by Lawrence Davis worked with RTOG staff to establish criteria and scoring for possible late effects from fast neutron radiation therapy . Investigators from the European Organization for Research and Treatment of Cancer ( EORTC ) , led by William Duncan of the Western General Hospital of Edinburgh , wished to have common toxicity criteria in anticipation of joint studies . RTOG Protocol 7929 , an international registry of patients treated with heavy particles , was started in 1980 . At the annual meetings of the international participants in particle studies , there were attempts to monitor interobserver variations in scoring effects in normal tissues and to seek consistency in reporting toxicity , but no publications document these efforts . The first prospect i ve trial to use the Late Morbidity Scoring Criteria was RTOG Protocol 8001 , a study of fast neutron therapy for malignant tumors arising in salivary gl and s. Although the RTOG began to use these criteria in reporting toxicity in patients enrolled in all studies from 198 1 ( beginning with RTOG Protocol 8 115 ) , the criteria only became a published part of protocol s in 1983 . At that time , statistical methods began to be used , which presented time-adjusted estimates of late effects , the rationale for which was described by Cox ( 1 ) . It is now considered st and ard to represent cumulative probabilities of late effects with methods similar to those for estimating local control and survival . The Acute Radiation Morbidity Scoring Criteria were developed in 1985 as complimentary to the Late Effects Scoring Criteria . The National Cancer Institute promulgated st and ard toxicity criteria in 1990 , but late effects were not considered . An abbreviated version of the RTOG/EORTC toxicity criteria was published by Winchester and Cox in 1992 as part of the St and ard for Breast Conservation Treatment . The current RTOG Acute Radiation Morbidity Scoring Criteria are presented in Table 1 . The RTOG/EORTC Late Radiation Morbidity Scoring Scheme is detailed in Table 2 . In both tables , 0 means an absence of radiation effects and 5 means the effects led to death . The OBJECTIVES In a prospect i ve clinical study , we tested the hypothesis that sparing the parotid gl and s may result in significant objective and subjective improvement of xerostomia in patients with head- and -neck cancers . The functional outcome 6 months after the completion of radiation therapy is presented . METHODS AND MATERIAL S From February 1997 to February 1999 , 41 patients with head- and -neck cancers were enrolled in a prospect i ve salivary function study . Inverse-planning intensity-modulated radiation therapy ( IMRT ) was used to treat 27 patients , and forward-planning three-dimensional radiation therapy in 14 . To avoid potential bias in data interpretation , only patients whose subm and ibular gl and s received greater than 50 Gy were eligible . Attempts were made to spare the superficial lobe of the parotid gl and s to avoid underdosing tumor targets in the parapharyngeal space ; however , the entire parotid volume was used to compute dose-volume histograms ( DVHs ) for this analysis . DVHs were computed for each gl and separately . Parotid function was assessed objective ly by measuring stimulated and unstimulated saliva flow before and 6 months after the completion of radiation therapy . Measurements were converted to flow rate ( mL/min ) and normalized relative to that before treatment . The corresponding quality -of-life ( QOL ) outcome was assessed by five questions regarding the patient 's oral discomfort and eating/speaking problems . RESULTS We observed a correlation between parotid mean dose and the fractional reduction of stimulated saliva output at 6 months after the completion of radiation therapy . We further examined whether the functional outcome could be modeled as a function of dose . Two models were found to describe the dose-response data well . The first model assumed that each parotid gl and is comprised of multiple independent parallel functional subunits ( corresponding to computed tomography voxels ) and that each gl and contributes equally to overall flow , and that saliva output decreases exponentially as a quadratic function of irradiation dose to each voxel . The second approach uses the equivalent uniform dose ( EUD ) metrics , which assumes loss of salivary function with increase in EUD for each parotid gl and independently . The analysis suggested that the mean dose to each parotid gl and is a reasonable indicator for the functional outcome of each gl and . The corresponding exponential coefficient was 0.0428/Gy ( 95 % confidence interval : 0.01 , 0.09 ) . The QOL questions on eating/speaking function were significantly correlated with stimulated and unstimulated saliva flow at 6 months . In a multivariate analysis , a toxicity score derived from the model based on radiation dose to the parotid gl and was found to be the sole significant predictive factor for xerostomia . Neither radiation technique ( IMRT vs. non-IMRT ) nor chemotherapy ( yes or no ) independently influenced the functional outcome of the salivary gl and s. CONCLUSION Sparing of the parotid gl and s translates into objective and subjective improvement of both xerostomia and QOL scores in patients with head- and -neck cancers receiving radiation therapy . Modeling results suggest an exponential relationship between saliva flow reduction and mean parotid dose for each gl and . We found that the stimulated saliva flow at 6 months after treatment is reduced exponentially , for each gl and independently , at a rate of approximately 4 % per Gy of mean parotid dose PURPOSE To determine whether prevention of hyposalivation after curative radiotherapy ( RT ) to the head and neck improves patients ' quality of life ( QOL ) . METHODS AND MATERIAL S Patients were to receive at least 50 Gy to 50 % of the volume of the major salivary gl and s , provide unstimulated and stimulated saliva sample s , and complete the University of Washington head- and -neck QOL tool before RT and 3 and 6 months after RT . Patients were r and omized to receive pilocarpine 5 mg or placebo q.i.d . RESULTS A total of 249 patients was r and omized between March 1998 and January 2000 . Of these , 214 were eligible for QOL analysis . Patients were evenly distributed between arms by race , gender , tobacco use , tumor site , T stage ( 50 % T2-T3 ) , and salivary function . A Karnofsky performance status of 90 % was more common in the pilocarpine arm . Twenty percent of the patients on the pilocarpine arm and 29 % of the patients on the placebo arm were taking nutritional supplements . The placebo arm patients had greater mouth pain and chewing difficulties . Compliance for the QOL tool at 3 and 6 months was 65 % and 50 % , respectively . Despite statistically significant ( p = 0.047 and p = 0.049 , respectively ) preservation of salivary function in the pilocarpine arm , patients on the pilocarpine arm reported difficulties with swallowing ( 75 % ) , activity ( 80 % ) , hyposalivation ( 64 % ) , and taste ( 81 % ) . No difference was noted between arms at 3 months in mucositis scores , with both arms demonstrating increased requirement for oral nutrients . CONCLUSION Objective prevention of hyposalivation did not affect patients ' assessment of salivary function or QOL because of the greater impact mucositis plays in QOL after RT PURPOSE To determine the relationship between quality of life ( QOL ) and xerostomia over time for patients undergoing radiotherapy ( RT ) for head- and -neck cancer in a prospect i ve clinical trial . METHODS AND MATERIAL S Patients with head- and -neck cancer were r and omized to pilocarpine ( n = 65 ) vs. placebo ( n = 65 ) during RT . QOL was measured using the McMaster Head and Neck Radiotherapy Question naire ( HNRQ ) . Xerostomia was measured on a linear analog scale . No statistically significant differences were observed between arms ; all 130 patients were analyzed together . RESULTS Baseline QOL data were obtained for 98.5 % of participants . The baseline HNRQ score of 5.7 declined significantly to 4.0 ( p < 0.0001 ) by RT Week 6 and returned to baseline ( 5.8 ) by 6 months after treatment . This represents a large , clinical ly important change of 1.7 of 7 ( 24 % ; effect size 1.34 ) . The decline in HNRQ score during RT paralleled the onset of xerostomia on the linear analog scale ( r = 0.36 at 1 month ) . After treatment , the QOL scores recovered without improvement in xerostomia . The trajectory of the linear analog scale score resembled that of the HNRQ 's single xerostomia question ( r = 0.75 at 1 month ) . CONCLUSION Quality of life recovers to baseline after RT , despite persistent xerostomia . Either a response shift occurs or xerostomia in the absence of acute mucositis has a relatively small influence on overall QOL |
12,829 | 19,812,102 | This review demonstrates that Dutch evidence -based clinical guidelines can be effective in improving the process and structure of care .
The high level of variation in effects across recommendations suggests that implementation strategies tailored to individual recommendations within the guideline are needed to establish relevant improvements in healthcare . | BACKGROUND Evidence -based clinical guidelines aim to improve the quality of care .
In The Netherl and s , considerable time and effort have been invested in the development and implementation of evidence -based guidelines since the 1990s .
Thus far , no review s are available on their effectiveness .
The primary aim of this article was to assess the evidence for the effectiveness of Dutch evidence -based clinical guidelines in improving the quality of care . | OBJECTIVE To assess the effects of a Dutch national prevention programme , aim ed at general practitioners ( GPs ) , on the adherence to organizational guidelines for effective cervical cancer screening in general practice . To identify the characteristics of general practice s determining success . DESIGN A prospect i ve question naire study with pre- and post-measurement ( before and 15 months after the introduction of the national programme ) . SETTING AND STUDY PARTICIPANTS A r and om sample of one-third of all 4758 Dutch general practice s. One GP was asked to participate per practice . INTERVENTION A national GP prevention programme to improve population -based prevention of cervical cancer combining various methods for quality improvement in general practice , performed on a national , district and practice level . Outreach visitors were a key strategy in bringing about behavioural changes . MAIN OUTCOME MEASURES The proportion of practice s adhering to 10 recommendations ( in four guidelines ) to organize effective cervical cancer screening . RESULTS After 15 months , all Dutch practice s showed significant improvement in adherence to nine out of 10 recommendations . Two recommendations , in particular ' identifying women who should be medically excluded from screening ' and ' sending a reminder to non-compliers ' showed the largest absolute increases of 26 % and 33 % , respectively . Besides more intensive support of outreach visitors , practice characteristics such as ' computerization ' and ' delegation of many clinical tasks to the practice assistant ' were important in improving the adherence to guidelines . CONCLUSION The national programme , with a combination of various methods for quality improvement , appeared to be effective in improving the organization of cervical screening in general practice . Computerization and , to a lesser extent , delegation of many clinical tasks to the practice assistant and more intensive support to practice s , positively influenced the effectiveness of the national programme Objectives : To evaluate the effect on the process of care of an active strategy to implement clinical guidelines on physiotherapy for low back pain . Design : A cluster r and omised controlled trial comparing an active strategy with st and ard dissemination . Setting : Primary care physiotherapy practice s. Participants : 113 physiotherapists were r and omly allocated to receive the guidelines by mail ( control group ) or to receive an additional active strategy ( intervention group ) which consisted of a multifaceted programme including education , discussion , role playing , feedback , and reminders . Main outcome measures : Adherence to the guidelines was measured by means of individual patients ’ forms recording the treatment completed by the physiotherapist . The forms were assessed using an algorithm based on the number of treatment sessions , treatment goals , interventions , and patient education . Results : Physiotherapists in the intervention group more often correctly limited the number of treatment sessions for patients with a normal course of back pain ( OR 2.39 ; 95 % CI 1.12 to 5.12 ) , more often set functional treatment goals ( OR 1.99 ; 95 % CI 1.06 to 3.72 ) , more often used mainly active interventions ( OR 2.79 ; 95 % CI 1.19 to 6.55 ) , and more often gave adequate patient education ( OR 3.59 ; 95 % CI 1.35 to 9.55 ) . They also adhered more to all four criteria ( OR 2.05 ; 95 % CI 1.15 to 3.65 ) . Conclusions : The active strategy moderately improved adherence to the guidelines . Active strategies are recommended to implement the clinical guidelines on physiotherapy for low back pain BACKGROUND There is still only limited underst and ing of whether and why interventions to facilitate the implementation of guidelines for improving primary care are successful . It is therefore important to look inside the ' black box ' of the intervention , to ascertain which elements work well or less well . AIM To assess the associations of key elements of a nationwide multifaceted prevention programme with the successful implementation of cervical screening guidelines in general practice . DESIGN OF STUDY A nationwide prospect i ve cohort study . SETTING A r and om sample of one-third of all 4,758 general practice s in The Netherl and s ( n = 1,586 ) . METHOD General practitioners ( GPs ) in The Netherl and s were exposed to a two- and -a-half-year nationwide multifaceted prevention programme to improve the adherence to national guidelines for cervical cancer screening . Adherence to guidelines at baseline and after the intervention and actual exposure to programme elements were assessed in the sample using self-administered question naires . RESULTS Both baseline and post-measurement question naires were returned by 988 practice s ( response rate = 62 % ) . No major differences in baseline practice characteristics between study population , non-responders , and all Netherl and s practice s were observed . After the intervention all practice s improved markedly ( P<0.001 ) in their incorporation of nine out of 10 guideline indicators for effective cervical screening into practice . The most important elements for successful implementation were : specific software modules ( odds ratios and 95 % confidence intervalsfor all nine indicators ranged from OR = 1.85 [ 95 % CI = 1.24 - 2.77 ] to OR = 10.2 [ 95 % CI = 7.58 - 14.1 ] ) ; two or more ' practice visits ' by outreach visitors ( ORs and 95 % CIs for six indicators ranged from OR = 1.46 [ 95 % CI= 1.01 - 2.12 ] to OR = 2.35 [ 95 % CI = 1.63 - 3.38 ] ) ; and an educational programme for practice assistants ( ORs and 95 % CIs for four indicators ranged from OR = 1.57 [ 95 % CI = 1.00 - 1.92 ] to OR = 1.90 [ 95 % CI = 1.25 - 2.88 ] ) . CONCLUSION A multifaceted programme targeting GPs , including facilitating software modules , outreach visits , and educational sessions for PAs , contributes to the successful implementation of national guidelines for cervical screening BACKGROUND AND PURPOSE An active strategy was developed for the implementation of the clinical guidelines on physical therapy for patients with low back pain . The effect of this strategy on patients ' physical functioning , coping strategy , and beliefs regarding their low back pain was studied . SUBJECTS One hundred thirteen primary care physical therapists treated a total of 500 patients . METHODS The physical therapists were r and omly assigned to 1 of 2 groups . The control group received the guidelines by mail ( st and ard passive method of dissemination ) . The intervention group , in contrast , received an additional active training strategy consisting of 2 sessions with education , group discussion , role playing , feedback , and reminders . Patients with low back pain , treated by the participating therapists , completed question naires on physical functioning , pain , sick leave , coping , and beliefs . RESULTS Physical functioning and pain in the 2 groups improved substantially in the first 12 weeks . Multilevel longitudinal analysis showed no differences between the 2 groups on any outcome measure during follow-up . DISCUSSION AND CONCLUSION The authors found no additional benefit to applying an active strategy to implement the physical therapy guidelines for patients with low back pain . Active implementation strategies are not recommended if patient outcomes are to be improved OBJECTIVE To evaluate the feasibility and implementation needs of a cholesterol guideline by assessing the effectiveness of simple dissemination as well as extensive implementation of this guideline on actual performance of general practitioners ( GPs ) . DESIGN R and omized controlled trial . SETTING AND SUBJECTS Thirty-two Dutch GPs in 20 general practice s , 3950 patient records . INTERVENTIONS Guideline dissemination to all 32 GPs , and a 5-month programme for improvement in the intervention group . This programme was developed after barriers to working according to the guideline had been investigated , and consisted of group education , desktop supportive material s , feedback on performance , and face-to-face instruction on location . MAIN OUTCOME MEASURES The outcome parameters were defined as quality of selective case finding and quality of diagnostic procedures , and were measured by chart audit . RESULTS The quality of selective case finding , especially the targeting of cholesterol testing to those with positive cardiovascular risk profiles , did not improve following intervention . Performance of the procedure necessary to diagnose hypercholesterolaemia even deteriorated . The quantity of cholesterol testing increased in both groups , but this was probably explained by the increased availability of desktop cholesterol analysers . CONCLUSIONS Neither simple dissemination nor an intensive programme for improvement had measurable impact on actual performance on working according to the cholesterol guideline . Both the validity and the opinion about feasibility of the guideline in daily practice deserve more attention during guideline development OBJECTIVE : To study the effectiveness of an intensive small group education and peer review programme aim ed at implementing national guidelines on asthma/chronic obstructive pulmonary disease ( COPD ) on care provision by general practitioners ( GPs ) and on patient outcomes . DESIGN : A r and omised experimental study with pre-measurement and post-measurement ( after one year ) in an experimental group and a control group in Dutch general practice . SUBJECTS AND INTERVENTION : Two groups of GPs were formed and r and omised . The education and peer review group ( 17 GPs with 210 patients ) had an intervention consisting of an interactive group education and peer review programme ( four sessions each lasting two hours ) . The control group consisted of 17 GPs with 223 patients ( no intervention ) . MAIN OUTCOME MEASURES : Knowledge , skills , opinion about asthma and COPD care , presence of equipment in practice ; actual performance about peakflow measurement , non-pharmacological and pharmacological treatment ; asthma symptoms ( Dutch Medical Research Council ) , smoking habits , exacerbation ratio , and disease specific quality of life ( QOL-RIQ ) . Data were collected by a written question naire for GPs , by self recording of consultations by GPs , and by a written self administered question naire for adult patients with asthma/ COPD . RESULTS : Data from 34 GP question naires , 433 patient question naires , and recordings from 934 consultations/visits and 350 repeat prescriptions were available . Compared with the control group there were only significant changes for self estimated skills ( + 16 % , 95 % confidence interval 4 % to 26 % ) and presence of peakflow meters in practice ( + 18 % , p < 0.05 ) . No significant changes were found for provided care and patient outcomes compared with the control group . In the subgroup of more severe patients , the group of older patients , and in the group of patients not using anti-inflammatory medication at baseline , no significant changes compared with the control group were seen in patient outcomes . CONCLUSION : Except for two aspects , intensive small group education and peer review in asthma and COPD care do not seem to be effective in changing relevant aspects of the provided care by GPs in accordance with guidelines , nor in changing patients ' health status OBJECTIVE To assess the evidence for the effectiveness of clinical practice guidelines ( CPGs ) in improving patient outcomes in primary care . DATA SOURCES A search of the MEDLINE , HEALTHPLAN , CINAHL and FAMLI data bases was conducted to identify studies published between Jan. 1 , 1980 , and Dec. 31 , 1995 , concerning the use of guidelines in primary medical care . The keywords used in the search were " clinical guidelines , " " primary care , " " clinical care , " " intervention , " " r and omized controlled trial " and " effectiveness . " STUDY SELECTION Studies of the use of CPGs were selected if they involved a r and omized experimental or quasi-experimental method , concerned primary care , were related to clinical care and examined patient outcomes . Of 91 trials of CPGs identified through the search , 13 met the criteria for inclusion in the critical appraisal . DATA EXTRACTION The following data were extracted , when possible , from the 13 trials : country and setting , number of physicians , number of patients ( and the proportion followed to completion ) , length of follow-up , study method ( including r and om assignment method ) , type of intervention , medical condition treated and effect on patient outcomes ( including clinical and statistical significance , with confidence intervals ) . DATA SYNTHESIS The most common conditions studied were hypertension ( 7 studies ) , asthma ( 2 studies ) and cigarette smoking ( 2 studies ) . Four of the studies followed nationally developed guidelines , and 9 used locally developed guidelines . Six studies involved computerized or automated reminder systems , whereas the others relied on small-group workshops and education sessions . Only 5 of the 13 trials ( 38 % ) produced statistically significant results . CONCLUSION There is very little evidence that the use of CPGs improves patient outcomes in primary medical care , but most studies published to date have used older guidelines and methods , which may have been insensitive to small changes in outcomes . Research is needed to determine whether the newer , evidence -based CPGs have an effect on patient outcomes OBJECTIVE To assess the long-term effectiveness of a quality improvement program on care provided and patient outcomes in patients with diabetes . RESEARCH DESIGN AND METHODS A nonr and omized trial was performed with 312 patients with type 2 diabetes in the intervention group and 77 patients with type 2 diabetes in the reference group . The follow-up period was 42 months . The quality improvement program focused on improving both the provision of diabetes care and the patient outcomes . The program consisted of clinical practice guidelines , postgraduate education , audit and feedback , templates to register diabetes care , and a recall system . Data on the care provided were abstract ed from medical records . Main outcomes on the provision of care were annual number of patient visits , blood pressure , and HbA(1c ) and blood lipid levels . Main patient outcomes were blood pressure and HbA(1c ) and blood lipid levels . Multilevel analysis was used to adjust for dependency between repeated observations within one patient and for clustering of patients within general practice s. RESULTS Patients in the intervention group received care far more in accordance with the guidelines than patients in the reference group . Odds ratios ranged from 2.43 ( 95 % CI 1.01 - 5.82 ) for the measurement of urine albumin to 12.08 ( 4.70 - 31.01 ) for the measurement of blood pressure . No beneficial effect was found on any patient outcome . CONCLUSIONS The quality improvement program improved the provision of diabetes care , but this was not accompanied by any effect on patient outcomes OBJECTIVES : To assess the effects of outreach visits by trained nurse facilitators on the organisation of services used to prevent cardiovascular disease . To identify the characteristics of general practice s that determined success . DESIGN : A non-r and omised controlled trial of two methods of implementing guidelines to organise prevention of cardiovascular disease : an innovative outreach visit method compared with a feedback method . The results in both groups were compared with data from a control group . SETTING AND SUBJECTS : 95 general practice s in two regions in The Netherl and s. INTERVENTIONS : Trained nurse facilitators visited practice s , focusing on solving problems in the organisation of prevention . They applied a four step model in each practice . The number of visits depended on the needs of the practice team . The feedback method consisted of the provision of a feedback report with advice specific to each practice and st and ardised instructions . MAIN OUTCOME MEASURES : The proportion of practice s adhering to 10 different guidelines . Guidelines were on the detection of patients at risk , their follow up , the registration of preventive activities , and teamwork within the practice . RESULTS : Outreach visits were more effective than feedback in implementing guidelines to organise prevention . Within the group with outreach visits , the increase in the number of practice s adhering to the guidelines was significant for six out of 10 guidelines . Within the feedback group , a comparison of data before and after intervention showed no significant differences . Partnerships and practice s with a computer changed more . CONCLUSION : Outreach visits by trained nurse facilitators proved to be effective in implementing guidelines within general practice s , probably because their help was practical and design ed for the individual practice , guided by the wishes and capabilities of the practice team Objective : To evaluate the effects of feedback reports combined with outreach visits from trained non-physicians on the clinical decision making of general practitioners ( GPs ) in cardiovascular care . Design : Pragmatic cluster controlled trial with r and omisation of practice s to support ( intervention group ) or no special attention ( control group ) ; analysis after 2 years . Setting : 124 general practice s in The Netherl and s. Participants : 185 GPs . Main outcome measures : Compliance rates for 12 evidence -based indicators for the management of patients with hypertension , hypercholesterolaemia , angina pectoris , or heart failure . The evaluation relied on the prospect i ve recording of patient encounters by the participating GPs . Results : The GPs reported 30 101 clinical decisions at baseline and 22 454 decisions after the intervention . A significant improvement was seen for five of the 12 indicators : assessment of risk factors in patients with hypercholesterolaemia ( odds ratio 2.04 ; 95 % CI 1.44 to 2.88 ) or angina pectoris ( 3.07 ; 1.08 to 8.79 ) , provision of information and advice to patients with hypercholesterolaemia ( 1.58 , 1.17 to 2.13 ) or hypertension ( 1.55 , 1.35 to 1.77 ) , and checking for clinical signs of deterioration in patients with heart failure ( 4.11 , 2.17 to 7.77 ) . Single h and ed practice s , non-training practice s , and practice s with older GPs gained particular benefit from the intervention . Conclusions : Intensive support from trained non-physicians can alter certain aspects of the clinical decision making of GPs in cardiovascular care . The effect is small and the strategy needs further development OBJECTIVES Misuse of antibiotics in surgical prophylaxis is still quite common . The objectives of this study were to reduce the quantity and improve the quality of surgical prophylaxis and to reduce costs . METHODS Prospect i ve multi-site study of elective procedures in 13 Dutch hospitals . The quality of prophylaxis was audited before and after an intervention consisting of performance feedback and implementation of national clinical practice guidelines . Process outcome parameters were antibiotic choice , duration , timing , antibiotic volume and costs . Segmented regression analysis was used to estimate the effect size of the intervention . Patient outcome was documented by the incidence of surgical site infections ( SSI ) . RESULTS Before the intervention , 1763 procedures were recorded and 2050 thereafter . Antimicrobial use decreased from 121 to 79 DDD ( defined daily doses)/100 procedures and costs reduced by 25 % per procedure . After the intervention , antibiotic choice was inappropriate in only 37.5 % of the cases instead of in 93.5 % expected cases had the intervention not occurred . Prolonged prophylaxis was observed in 31.4 % instead of 46.8 % expected cases and inappropriate timing in 39.4 % instead of the expected 51.8 % . Time series analysis showed that all improvements were statistically significant ( P < 0.01 ) and that they could be fully attributed to the intervention . The overall SSI rates before and after intervention were 5.4 % ( 95 % CI : 4.3 - 6.5 ) and 4.6 % ( 95 % CI : 3.6 - 5.4 ) , respectively . CONCLUSIONS The intervention led to improved quality of surgical prophylaxis and to reduced antibiotic use and costs without impairment of patient outcome BACKGROUND Limited data exist on the most effective approach to increase the quality of antibiotic use for lower respiratory tract infections at hospitals . METHODS One thous and nine hundred six patients with community-acquired pneumonia or an exacerbation of chronic obstructive pulmonary disease ( acute exacerbation of chronic bronchitis ) were included in a cluster-r and omized , controlled trial at 6 medium-to-large Dutch hospitals . A multifaceted guideline -implementation strategy that was tailored to baseline performance and considered the barriers in the target group was used . Principal outcome measures were ( 1 ) guideline -adherent antibiotic prescription , ( 2 ) adaptation of dose and dose interval of antibiotics according to renal function , ( 3 ) switches in therapy , ( 4 ) streamlining of therapy , and ( 5 ) Gram staining and culture of sputum sample s. Secondary process outcomes were applicable to community-acquired pneumonia ( e.g. , timely administration of antibiotics ) or acute exacerbation of chronic bronchitis ( e.g. , not prescribing macrolides ) . RESULTS The rate of guideline -adherent antibiotic prescription increased from 50.3 % to 64.3 % in the intervention hospitals ( odds ratio [ OR ] , 2.63 ; 95 % confidence interval [ CI ] , 1.57 - 4.42 ; P=.0008 ) . The rate of adaptation of antibiotic dose according to renal function increased from 79.4 % to 95.1 % in the intervention hospitals ( OR , 7.32 ; 95 % CI , 2.09 - 25.7 ; P=.02 ) . The switch from intravenous to oral therapy improved more in the control hospitals ( from 53.3 % to 71.9 % ) than in the intervention hospitals ( from 74 % to 83.6 % ) . The change from broad-spectrum empirical therapy to pathogen-directed therapy improved by 5.7 % in the intervention hospitals ( P = not significant ) . Fewer sputum sample s were obtained from both the intervention group ( rate of sputum sample s obtained decreased from 55.8 % to 53.1 % ) and the control group ( rate of sputum sample s obtained decreased from 49.6 % to 42.7 % ) . Timely administration of antibiotics for community-acquired pneumonia increased significantly in the intervention group ( from 55.2 % to 62.9 % ; OR , 2.49 ; 95 % CI , 1.11 - 5.57 ; P=.026 ) . CONCLUSIONS With regard to some important aspects , tailoring interventions to change antibiotic use improved the quality of treatment for patients hospitalized with lower respiratory tract infection AIM To determine the effect of a distance learning programme on general practice management of men with lower urinary tract symptoms ( LUTS ) . METHODS A cluster r and omised controlled trial was performed . General practitioners ( GPs ) were r and omised to a distance learning programme accompanied with educational material s or to a control group only receiving mailed clinical guidelines on LUTS . Clinical management was considered as outcome . RESULTS Sixty-three GPs registered care management of 187 patients older than 50 years attending the practice because of LUTS . The intervention group showed a lower referral rate to a urologist ( OR : 0.08 ( 95 % CI : 0.02 - 0.40 ) ) , but no effect on PSA testing or prescription of medication . PSA testing tended to be requested more frequently by intervention group GPs . Secondary analysis showed patients in the intervention group received more educational material s ( OR : 75.6 ( 95 % CI : 13.60 - 419.90 ) ) . CONCLUSIONS The educational programme had impact on clinical management without changing PSA testing . Distance learning is an promising method for continuing education . PRACTICE IMPLICATION S Activating distance learning packages are a potentially effective method for improving professional performance . Emotional matters as PSA testing probably need a more complex approach Background : We implemented a comprehensive intervention program targeting general practice staff , that proved successful in optimizing practice organization and clinical decision-making . In this paper , health-related quality of life ( HRQL ) is investigated as a clinical outcome . Objective : To evaluate the effect of the implementation of an intervention program on the HRQL in patients at high cardiovascular risk . Research design : R and omized controlled trial . Intervention practice s ( n = 62 ) received a comprehensive intervention program ( by means of outreach visitors ) lasting 21 months . HRQL of patients at high cardiovascular risk was assessed by the MOS 36-Item Short-Form Health Survey ( SF-36 ) , at baseline and after intervention . Three patient categories were distinguished : diabetes mellitus , cardiovascular disease and hypertension . Results : HRQL deteriorated in all respondents , but more pronounced in the control group . In diabetes patients the differences between intervention and control group were significant for the Vitality and Mental Health scales , with mean difference in change of 3.93 ( 95 % CI : 1.08–6.78 ) and 3.71 ( 95 % CI : 0.73–6.68 ) , respectively . Patients with cardiovascular disease had significantly different changes on three scales : physical functioning ( 3.57 , 95 % CI : 0.71–6.43 ) , vitality ( 3.01 , 95 % CI : 0.72–5.30 ) and social functioning ( 3.96 , 95 % CI : 0.50–7.42 ) . In patients with hypertension , there were no differences between the intervention and control group . Conclusion : Our comprehensive intervention program result ed in changes in HRQL on several domains , particularly in patients with diabetes and cardiovascular disease AIMS To evaluate the effectiveness of a multifaceted intervention to improve the clinical decision making of general practitioners ( GPs ) for patients with diabetes . To identify practice characteristics which predict success . METHODS Cluster r and omized controlled trial with 124 practice s and 185 GPs in The Netherl and s. The intervention group received feedback reports and support from a facilitator ; the control group received no special attention . Outcome measures were the compliance rates with evidence -based recommendations pertaining to discussion of body weight control , discussion of problems with medication , blood pressure measurement , foot examination , eye examination , initiating anti-diabetic medication or increasing the dosage in cases of uncontrolled blood glucose , and scheduling a follow-up appointment . RESULTS The GPs reported on their clinical decision making in 1410 consultations with Type 2 diabetic patients at baseline and 1449 consultations after the intervention period . The intervention result ed in statistically significant improvement for two of the seven outcome measures : foot examination ( odds ratio 1.68 ; 95 % confidence interval 1.19 - 2.39 ) and eye examination ( 1.52 ; 1.07 - 2.16 ) . Discussion of problems with medication showed a near significant trend towards increased benefit for the intervention group ( 1.52 ; 0.99 - 2.32 ) . Practice characteristics were not found to be related to the success of the intervention . CONCLUSIONS Feedback reports with support from facilitators appear to increase rates of foot examination and eye examination in general practice . Alternative interventions should be explored to improve the pursuit of metabolic control by GPs Study Design . Cluster r and omized controlled trial for a multifaceted implementation strategy . Objectives . To assess the effectiveness of tailored interventions ( multifaceted implementation strategy ) to implement the Dutch low back pain guideline for general practitioners with regard to adherence to guideline recommendations . Summary of Background Data . Guidelines for the management of low back pain in primary care have been developed in various countries , but little is known about the optimal implementation strategy . A multifaceted implementation strategy was developed to overcome identified barriers to the implementation of the Dutch low back pain guideline for general practitioners . Methods . General practitioners were r and omized to an intervention or a control group . The general practitioners in the intervention group ( n = 21 ) received tailored interventions consisting of the Dutch low back pain guideline for general practitioners , a 2-hour educational and clinical practice workshop ; two scientific articles on low back pain management ; the guideline for occupational physicians ; a tool for patient education ; and a tool for reaching agreement on low back care with physical , exercise , and manual therapists . The control group ( n = 20 ) received no intervention . The participating general practitioners were asked to recruit consecutive patients with a new episode of low back pain as the main reason for consultation . General practitioners completed registration forms of each individual consultation with regard to the main outcome measures : advice and information , referral to other health-care providers , and prescription of medication . Results . Forty-one of the 67 r and omized general practitioners reported on a total of 616 consultations for 531 patients with nonspecific low back pain . The advice and explanation provided by the general practitioners , the prescription of paracetamol or nonsteroidal anti-inflammatory drugs , and prescription of pain medication on atime contingent or a pain contingent basis showed no statistically significant differences between the intervention and control groups . There were also no differences in overall referral rate . However , in follow-up consultations fewer patients were referred to a physical or exercise therapist by the general practitioners in the intervention group than in the control group . Conclusions . The multifaceted intervention strategy modestly improved implementation ( for parts of the recommendations in ) the Dutch low back pain guideline by general practitioners and produced small concomitant changes in patient management . The implementation strategy produced fewer referrals to therapists during follow-up consultations OBJECTIVE To assess t he effectiveness of a nation-widemultifaceted intervention programme involving general practitioners ( GPs ) on influenza immunisation practice . DESIGN Pragmatic before-after trial using pre- and post-measurement question naires . SETTING AND SUBJECTS R and om sample of Dutch general practice s. INTERVENTION During a 2.5-year period ( 1995 - 1997 ) a variety of methods was implemented to enhance physician adoption of the immunisation guideline , including employment of facilitators , information-based methods , small-group consensus meetings , individual instructions and introduction of supportive computer software . MAIN OUTCOME MEASURES Influenza immunisation practice and influenza vaccine uptake . RESULTS In 988 practice s all influenza vaccination characteristics markedly improved from 1995 to 1997 . The most significant changes were found in computerised marking of high-risk patients ( from 54 % to 82 % of practice s ) , computerised selection ( 41 % to 77 % ) and sending personal reminders ( 40 % to 77 % ) . Vaccine uptake increased from 9 % to 16 % of the practice population ( 78 % increase , p < 0.001 ) . Uptake was most prominent in urban and single-h and ed practice s and in those with more patients insured through the National Health Service , low GP workload and low baseline uptake . CONCLUSION Our data suggest that a co-ordinated approach involving primary care physicians can succeed in enlarging the public health impact of a population -based preventive measure The objective of this study was twofold , namely to evaluate the effectiveness of a dental clinical practice guideline on the management of asymptomatic impacted lower third molars ( i ) on referral rates and ( ii ) on dentists ' change in knowledge . A two-arm cluster r and omized controlled trial , with pre- and post-test assessment s , was conducted . A guideline was implemented by multifaceted interventions ( i.e. feedback , reminders , and an interactive meeting ) . The effect was evaluated after 1 yr by repeating the baseline question naire and by monitoring the number of patients who were referred for removal of their asymptomatic impacted m and ibular third molars . Instruments were question naires for detecting changes in knowledge , patient records , and panoramic radiographs . The knowledge of dentists regarding asymptomatic m and ibular third molar management was found to increase significantly in the intervention group as compared to the control group . There was no statistically significant difference between the groups in guideline -consistent patient referral rates at the post-test assessment . It was concluded that the methodology employed for dissemination and implementation of a clinical practice guideline on asymptomatic m and ibular third molar management improves dentists ' knowledge on this topic and is effective in improving decision-making in simulated cases ; however , no clinical effect was demonstrated BACKGROUND Multifaceted interventions improve the quality of preventive cardiovascular care in general practice when applied in small-scale research trials . AIM To test the transferability of observations from research trials on preventive cardiovascular care to a real-world situation and , therefore , evaluate the effectiveness of a nationwide project with a large number of practice s. The intervention comprised a combination of conferences , dissemination of manuals , and support from trained non-physicians during outreach visits . DESIGN OF STUDY A controlled before- and -after trial with two arms : multifaceted support versus no special attention . Analysis after 2 years . SETTING 617 general practice s in The Netherl and s. METHOD Outcomes measures were the compliance rates for 15 indicators . Structure-of-care indicators included the use of reminders , specific computer files , written protocol s , and special clinics . Process-of-care indicators included the assessment of modifiable risk factors and use of a minimal contact intervention ( MCI ) for smoking cessation . Compliance of general practitioners ( GPs ) was assessed using self-administered question naires . RESULTS The intervention group improved on all eight of the structure-of-care indicators when compared to the control group . A positive effect was also found on the extent to which the GPs measured blood pressure in 60-year-old patients and on the use of an MCI for smoking cessation . No effect was found on the completeness of the risk-factor profiles that the GPs assessed in specific groups of high-risk patients . CONCLUSION The nationwide intervention appeared to improve certain aspects of preventive cardiovascular care . Nevertheless , the National Association of GPs decided to stop the project . This decision was made within the context of discussion s about the heavy workloads and insufficient incomes being experienced by GPs CONTEXT During the past decade , several guidelines on the management of chronic obstructive pulmonary disease and asthma have been developed . However , strategies for implementing these guidelines have not been systematic ally evaluated . OBJECTIVE To test a quality system intended to improve general practitioners ' compliance with recently established guidelines . DESIGN Before-after study with concurrent controls . UNIT OF ANALYSIS : 19 general medical practice s in the Netherl and s ( 14 intervention practice s and 5 control practice s ) . INTERVENTION A quality system with five components : identification of barriers , documentation , education , feedback , and peer review . PATIENTS Out patients 16 to 70 years of age with asthma or chronic obstructive pulmonary disease . MEASUREMENTS The number of consultations for respiratory symptom monitoring , measurement of peak expiratory flow rate , prescription of anti-inflammatory agents , monitoring of medication compliance and inhalation technique , and influenza vaccination . RESULTS The percentage of patients who had two or more consultations per year increased significantly in the intervention practice s ( median , 27 % of patients before the intervention vs 82 % of patients after the intervention ; P < 0.01 ) , as did the percentage of patients who had at least one measurement of peak expiratory flow rate ( median , 10 % of patients before the intervention vs 84 % of patients after the intervention ; P < 0.01 ) . The percentage of patients who received a prescription for anti-inflammatory agents did not increase significantly . No significant changes were seen in the control practice s. Physicians in the intervention practice s were more likely to monitor medication compliance and inhalation technique . No difference was found in frequency of influenza vaccination . CONCLUSION The quality system improved guideline compliance in some areas but not in others Objective : To describe the short-term and long-term effects of a hospital-wide pressure ulcer prevention and treatment guideline on both the incidence and the time to the onset of pressure ulcers in critically ill patients . Design : Prospect i ve cohort study . Setting : Adult intensive care department of a university medical center . Patients : Critically ill patients ( n = 399 ) . Interventions : A guideline for pressure ulcer care was implemented on all intensive care units . The attention of nurses for timely transfer to a specific pressure-reducing device was an important part of this guideline . Measurements and Main Results : Patient characteristics , demographics , pressure ulcer risk profile at admission , daily pressure ulcer grading , and type of mattress were determined to describe the short-term and long-term effects 3 and 12 months after the implementation . The incidence density of pressure ulcers grade II – IV decreased from 54 per 1000 patient days at baseline to 32 per 1000 days ( p = .001 ) 12 months after the implementation . The median pressure ulcer-free time increased from 12 days to 19 days ( hazard rate ratio , 0.58 ; p = .02 ) . After adjustment for differences in risk factors in a Cox proportional hazard model , the number of preventive transfers to special mattresses was the strongest indicator for the decreased risk of pressure ulcers ( hazard rate ratio , 0.22 ; p < .001 ) . The number needed to treat to prevent one pressure ulcer during the first 9 days was six . Conclusions : The implementation of a guideline for pressure ulcer care result ed in a significant and sustained decrease in the development of grade II – IV pressure ulcers in critically ill patients . Timely transfer to a specific mattress ( i.e. , transfer before the occurrence of a pressure ulcer ) was the main indicator for a decrease in pressure ulcer development RATIONALE , AIMS AND OBJECTIVES Peer review groups are considered helpful for quality improvement in primary care . An interactive educational programme for small peer groups was developed , focusing on the implementation of newly developed treatment guidelines . The aim is to evaluate the effect of the programme on adherence to treatment guidelines in general practice . METHODS A cluster r and omized trial using a balanced incomplete block design was used ; one arm received a programme on treatment of chronic heart failure ( CHF ) , the other on hypertension treatment in diabetes mellitus type 2 ( T2DM ) . A r and om sample of 10 CHF and 10 T2DM patients per GP was drawn , for whom data were extracted from electronic patient records 1 years before and 6 months after the intervention . The outcomes were prescribing of ACE inhibitors , and antihypertensive treatment in T2DM . The effect was analysed separately for both programmes using multilevel regression models . RESULTS All 27 peer review groups in one region in the Netherl and s were r and omized , of which 16 participated . No significant effects were observed in the CHF group or in the T2DM group . The opportunity for change was limited , as only 53 % of the CHF patients and 60 % of the T2DM patients had a contact with their GP between the intervention and follow-up measurement . CONCLUSION The peer review programme was not successful for changing the treatment of chronic patients , although the programme focused on dealing with barriers perceived by the participants . Not all problems perceived can be solved in a peer group discussion OBJECTIVE To evaluate a project to implement guidelines on the management of patients with asthma or chronic obstructive pulmonany disease ( COPD ) in terms of the health outcomes of these patients . DESIGN A before- and -after study of 1 year with a non-r and omized but comparable reference group . SETTING General practice s in the Netherl and s. STUDY PARTICIPANTS Two-hundred and eighty patients from 14 practice s in the intervention group and 90 patients from five practice s in the reference group ( receiving usual care ) . INTERVENTION The project included a comprehensive implementation programme , involving identification of barriers , documentation of the care provided , specific education , feedback on compliance with the guidelines , and peer review . This project has been found to bring the process of care more in agreement with the guidelines . MAIN OUTCOME MEASURES Mean peak expiratory flow rate ( PEFR ) as a percentage of the predicted value , number of days with a diurnal variation in PEFR > or = 15 % , number of days with respiratory symptoms ( all recorded by patients for a period of 14 days ) , and perceived health status ( Nottingham Health Profile ) . RESULTS After 1 year , the intervention group showed statistically significant improvements with regard to the mean PEFR , the diurnal variation in PEFR , respiratory symptoms and the pain score of the Nottingham Health Profile . Comparing the changes within the intervention group with the changes within the reference group , only a positive effect of the intervention on the mean PEFR was found . CONCLUSION The comprehensive implementation programme improved the lung function and symptoms of asthma and COPD patients in the intervention group . However , in comparison with a reference group , the positive effect on the lung function was only small BACKGROUND Adequate care for patients with cardiovascular risks requires an adequate practice organization . Educational outreach visits are a promising approach to modifying professional behavior . We aim ed to assess whether the quality of cardiovascular preventive care in general practice can be improved through a comprehensive intervention implemented by an educational outreach visitor . METHODS After baseline measurements , general practice s ( n = 124 ) in the southern half of The Netherl and s were r and omly allocated to either intervention or control group . The intervention , based on the educational outreach model , comprised 15 practice visits over a period of 21 months and addressed a large number of issues around task delegation , availability of instruments and patient leaflets , record-keeping , and follow-up routines . Twenty-one months after the start of the intervention , postintervention measurements were performed . The difference between ideal and actual practice in each aspect of organizing preventive care was defined as a deficiency score . Primary outcome measure was the difference in deficiency scores before and after the intervention . RESULTS All practice s completed both baseline and postintervention measurements . The difference in change between intervention and control group adjusted for baseline was statistically significant ( P < 0.001 ) for each aspect of organizing preventive care . The largest absolute improvement was found for the number of preventive tasks performed by the practice assistant . CONCLUSIONS This study showed that a comprehensive intervention implemented by outreach visitors was effective in improving organization of cardiovascular preventive care in general practice Objective . Guidelines for primary care management of lower urinary tract symptoms in older men recommend shared decision making regarding the choice of treatment . In this study we aim ed to determine the costs and patient outcomes of an implementation strategy design ed to enhance uptake of these guidelines . Material and methods . The intervention comprised a distance learning programme for general practitioners , comprising evidence -based information , assessment of learning needs , a knowledge test and patient education material s. The control group only received the written guidelines . A cluster r and omized trial in 187 older male patients compared costs and outcomes in the two study groups . A healthcare perspective was taken in the economic evaluation , with a 3-month time horizon . The primary health outcome was patient-reported urinary symptoms at 3 months . Costs relating to the distance learning package and the healthcare provided were considered , using undiscounted st and ardized prices . Results . Patient-reported urinary symptoms at 3 months did not differ between the study groups : 66 % and 61 % with moderate symptoms and 7 % and 11 % with severe symptoms in the intervention and control groups , respectively . The mean total costs per patient were € 28.15 lower in the intervention group ( € 93.11 ) compared to the control group ( € 121.26 ) , mainly because of a lower number of referrals to the urologist . A bootstrap analysis showed an incremental cost-effectiveness ratio of € 111.98 ( 95 % CI –€423 to + € 329 ) . Conclusions . The distance learning programme did not change health outcomes , but it reduced costs in the first 3 months after an initial consultation compared to written guidelines . Studies with a longer follow-up period are needed |
12,830 | 11,248,841 | Results Postnatal steroid therapy is associated with an increase in cerebral palsy and neuro-developmental impairment .
The studies with less contamination show a greater effect of the steroids , consistent with a real direct toxic effect of steroids on the developing central nervous system .
Conclusions Postnatal pharmacologic steroid treatment for prevention or treatment of bronchopulmonary dysplasia is associated with dramatic increases in neuro-developmental impairment . | Background Recent reports have raised concerns that postnatal steroids may cause neuro-developmental impairment in preterm infants .
This systematic review was performed with the objective of determining whether glucocorticoid therapy , to prevent or treat bronchopulmonary dysplasia , impairs neuro-developmental outcomes in preterm infants . | OBJECTIVES To study whether early postnatal ( < 12 hours ) dexamethasone therapy reduces the incidence of chronic lung disease in preterm infants with respiratory distress syndrome . MATERIAL S AND METHODS A multicenter r and omized , double-blind clinical trial was undertaken on 262 ( saline placebo , 130 ; dexamethasone , 132 ) preterm infants ( < 2000 g ) who had respiratory distress syndrome and required mechanical ventilation shortly after birth . The sample size was calculated based on the 50 % reduction in the incidence of chronic lung disease when early dexamethasone is used , allowing a 5 % chance of a type I error and a 10 % chance of a type II error . For infants who received dexamethasone , the dosing schedules were : 0.25 mg/kg/dose every 12 hours intravenously on days 1 through 7 ; 0.12 mg/kg/dose every 12 hours intravenously on days 8 through 14 ; 0.05 mg/kg/dose every 12 hours intravenously on days 15 through 21 ; and 0 . 02 mg/kg/dose every 12 hours intravenously on days 22 through 28 . A st and ard protocol for respiratory care was followed by the participating hospitals . The protocol emphasized the criteria of initiation and weaning from mechanical ventilation . The diagnosis of chronic lung disease based on oxygen dependence and abnormal chest roentgenogram was made at 28 days of age . To assess the effect of dexamethasone on pulmonary inflammatory response , serial tracheal aspirates were assayed for cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha . All infants were observed for possible side effects , including hypertension , hyperglycemia , sepsis , intraventricular hemorrhage , retinopathy of prematurity , cardiomyopathy , and alterations in calcium homeostasis , protein metabolism , and somatic growth . RESULTS Infants in the dexamethasone group had a significantly lower incidence of chronic lung disease than infants in the placebo group either judged at 28 postnatal days ( 21/132 vs 40/130 ) or at 36 postconceptional weeks ( 20/132 vs 37/130 ) . More infants in the dexamethasone group than in the placebo group were extubated during the study . There was no difference between the groups in mortality ( 39/130 vs 44/132 ) ; however , a higher proportion of infants in the dexamethasone group died in the late study period , probably attributable to infection or sepsis . There was no difference between the groups in duration of oxygen therapy and hospitalization . Early postnatal use of dexamethasone was associated with a significant decrease in tracheal aspirate cell counts , protein , leukotriene B4 , and 6-keto prostagl and in F1alpha , suggesting a suppression of pulmonary inflammatory response . Significantly more infants in the dexamethasone group than in the placebo group had either bacteremia or clinical sepsis ( 43/132 vs 27/130 ) . Other immediate , but transient , side effects observed in the dexamethasone group are : an increase in blood glucose and blood pressure , cardiac hypertrophy , hyperparathyroidism , and a transient delay in the rate of growth . CONCLUSIONS In preterm infants with severe respiratory distress syndrome requiring assisted ventilation shortly after birth , early postnatal dexamethasone therapy reduces the incidence of chronic lung disease , probably on the basis of decreasing the pulmonary inflammatory process during the early neonatal period . Infection or sepsis is the major side effect that may affect the immediate outcome . Other observable side effects are transient . In view of the significant side effects and the lack of overall improvement in outcome and mortality , and the lack of long term follow-up data , the routine use of early dexamethasone therapy is not yet recommended A r and omized trial was conducted of dexamethasone therapy in infants with bronchopulmonary dysplasia who were dependent on respirators and were not progressing clinical ly despite conventional treatment . Babies were admitted to the study if they had a roentgenogram and clinical diagnosis of bronchopulmonary dysplasia , were 2 to 6 weeks in age , weighed less than 1,500 g , had made no progress in weaning for the preceding five days , and were free of sepsis , patent ductus arteriosus , and congenital heart disease , and had had no intravenous fat for at least 24 hours . After parental consent was obtained , infants were r and omly assigned to control or treatment groups . The study hypothesis was that with steroid treatment , babies could be weaned from the respirator within 72 hours and would show a significant improvement in lung compliance within that time . Sequential analysis exceeded criterion ( P less than .05 ) when seven consecutive untied pairs showed weaning with dexamethasone and failure to wean in control infants . Pulmonary compliance improved by 64 % in the treated group and 5 % in the control group ( P less than .01 ) . No significant intergroup differences were noted in mortality , length of hospital stay , sepsis , hypertension , hyperglycemia , or electrolyte abnormalities . Study design permits the conclusion that dexamethasone can produce substantial short-term improvement in lung function , often permitting rapid weaning from the respirator , but long-term efficacy and safety must be demonstrated by further investigations OBJECTIVE To test the hypothesis that early postnatal dexamethasone will reduce the incidence of death or chronic lung disease ( CLD ) in ventilated extremely low birth weight premature infants . DESIGN Multicenter r and omized double-blinded controlled clinical trial . SETTING A total of 42 neonatal intensive care units in the Vermont Oxford Network . PARTICIPANTS Infants weighing 501 to 1000 g were eligible for enrollment at 12 hours of age if they needed assisted ventilation , had received surfactant replacement therapy , were physiologically stable , had no obvious life-threatening congenital anomaly , and had blood cultures obtained and antibiotic therapy initiated . INTERVENTION Infants were r and omly assigned to dexamethasone or saline placebo . Intravenous dexamethasone was administered for 12 days according to the following dosing schedule : 0.5 mg/kg/d for 3 days , 0.25 mg/kg/d for 3 days , 0.10 mg/kg/d for 3 days , 0.05 mg/kg/d for 3 days . Infants in either group could receive treatment with selective late postnatal steroids beginning on day 14 of life if they were on assisted ventilation with supplemental oxygen greater than 30 % . OUTCOME MEASUREMENTS The primary outcome measure was CLD or death at 36 weeks postmenstrual age . RESULTS The study was stopped before completion of sample size goals because of concern about serious side effects in the early steroid treatment group . A total of 542 infants were enrolled ( early treatment N = 273 , control N = 269 ) . The 2 groups had similar demographic characteristics . No differences were noted in the primary outcome of CLD or death at 36 weeks postmenstrual age ( early treatment 50 % vs control : 53 % , relative risk : 0.93 ; 95 % confidence interval [ CI ] : 0.79 - 1.09 ) . Fewer infants who received early steroid treatment had a patent ductus arteriosus ( relative risk : 0.78 ; 95 % CI : 0.63 - 0.96 ) , and fewer infants in the early steroid group received indomethacin therapy ( relative risk : 0.74 ; 95 % CI : 0.64 - 0.86 ) or late steroid treatment ( relative risk : 0.69 ; 95 % CI : 0.58 - 0.81 ) . However , more infants who received early steroid treatment had complications associated with therapy including an increase in hyperglycemia ( relative risk : 1.29 ; 95 % CI : 1.13 - 1.46 ) and an increase in the use of insulin therapy ( relative risk : 1.62 ; 95 % CI : 1.36 - 1.94 ) . A trend toward increased gastrointestinal hemorrhage ( relative risk : 1.55 ; 95 % CI : 0.92 - 2.61 ) , gastrointestinal perforation ( relative risk : 1.53 ; 95 % CI : 0.89 - 2.61 ) , and an increased systolic blood pressure ( relative risk : 1.34 ; 95 % CI : 0.97 - 1.85 ) was noted . In infants receiving cranial ultrasound examinations , a marginal increase in periventricular leukomalacia was noted in the early steroid treatment group ( relative risk : 2.23 ; 95 % CI : 0.99 - 5.04 ) . Infants who received early steroid therapy had fewer days in supplemental oxygen but experienced poor weight gain . CONCLUSIONS A 12-day course of early postnatal steroid therapy given to extremely low birth weight infants did not decrease the risk of CLD or death at 36 weeks postmenstrual age and was associated with an increased risk of complications and poor weight gain OBJECTIVE To study the long term neurodevelopmental outcome of children who participated in a r and omised , double blind , placebo controlled study of early postnatal dexamethasone treatment for prevention of chronic lung disease . METHODS The original study compared a three day course of dexamethasone ( n = 132 ) with a saline placebo ( n = 116 ) administered from before 12 hours of age in preterm infants , who were ventilated for respiratory distress syndrome and had received surfactant treatment . Dexamethasone treatment was associated with an increased incidence of hypertension , hyperglycaemia , and gastrointestinal haemorrhage and no reduction in either the incidence or severity of chronic lung disease or mortality . A total of 195 infants survived to discharge and five died later . Follow up data were obtained on 159 of 190 survivors at a mean ( SD ) age of 53 ( 18 ) months . RESULTS No differences were found between the groups in terms of perinatal or neonatal course , antenatal steroid administration , severity of initial disease , or major neonatal morbidity . Dexamethasone treated children had a significantly higher incidence of cerebral palsy than those receiving placebo ( 39/80 ( 49 % ) v 12/79 ( 15 % ) respectively ; odds ratio ( OR ) 4.62 , 95 % confidence interval ( 95 % CI ) 2.38 to 8.98 ) . The most common form of cerebral palsy was spastic diplegia ( incidence 22/80 ( 28 % ) v 5/79 ( 6 % ) in dexamethasone and placebo treated infants respectively ; OR 4.45 , 95 % CI 1.95 to 10.15 ) . Developmental delay was significantly more common in the dexamethasone treated group ( 44/80 ( 55 % ) ) than in the placebo treated group ( 23/79 ( 29 % ) ; OR 2.87 , 95 % CI 1.53 to 5.38 ) . Dexamethasone treated infants had more periventricular leucomalacia and less intraventricular haemorrhage in the neonatal period than those in the placebo group , although these differences were not statistically significant . Eleven children with cerebral palsy had normal ultrasound scans in the neonatal period ; all 11 had received dexamethasone . Logistic regression analysis showed both periventricular leucomalacia and drug assignment to dexamethasone to be highly significant predictors of abnormal neurological outcome . CONCLUSIONS A three day course of dexamethasone administered shortly after birth in preterm infants with respiratory distress syndrome is associated with a significantly increased incidence of cerebral palsy and developmental delay OBJECTIVE We compared the effects of a policy of neonatal steroid administration versus placebo for babies chronically dependent on supplemental oxygen in terms of long-term health and development , judged at 3 years of age . DESIGN Double-blind r and omized controlled trial . SETTING Thirty-one centers in the United Kingdom , Irel and , Belgium , Germany , Canada , and the United States . PATIENTS Babies who were chronically dependent on supplemental oxygen between 2 and 12 weeks of age were recruited to the trial between 1986 and 1989 . Sixty-two children were known to have died , 23 before discharge from the hospital and 10 afterward in the active group , compared with 25 and 4 , respectively , in the placebo group . Information was available for 209 of the 212 eligible for follow-up ( 99 % ) . INTERVENTIONS A 1-week course of active dexamethasone phosphate 0.6 mg/kg/d ( dexamethasone base 0.5 mg/kg/d ) or saline placebo was given intravenously ( or orally , if no intravenous line ) . There was an option to give a second tapering 9-day course if relapse occurred after initial improvement . OUTCOME MEASURES Information about respiratory problems , growth , neurodevelopment and disability , infection , and health service use when the children were 3 years old was ascertained from question naires to general practitioners , health visitors , and parents ( and occasionally pediatricians ) . RESULTS About half the children in both groups had been admitted to the hospital for respiratory problems , with more in the active than the placebo group having at least five outpatient consultations for these problems over the 3 years . Overall , the children were below average in height , weight , and head circumference . About one fifth had cerebral palsy , 8 % some visual loss , and 16 % hearing loss ; 18 % needed or were anticipated to need special schooling . There were no clear differences between the r and omized groups . These overall conclusions were not altered by any of the prespecified secondary analyses . CONCLUSIONS Despite early benefits , there were no clear effects at 3 years of age . As 40 % of the placebo group eventually received open steroids , even a trial of this size has limited statistical power to detect a moderate effect of the policy . Regardless of r and om allocation , overall morbidity was high , confirming that babies with protracted dependence on supplemental oxygen are at high risk of childhood disability and poor health UNLABELLED BACKGROUND . Many extremely low birth weight infants ( < 1000 g ) show biochemical evidence of adrenal insufficiency in the first week of life , correlating with subsequent development of chronic lung disease ( CLD ) . METHODS We conducted a r and omized , double-masked , placebo-controlled pilot study to test whether early treatment with low-dose hydrocortisone for 12 days ( 1 mg/kg/day for 9 days followed by.5 mg/kg/day for 3 days ) , begun before 48 hours of life , would increase the likelihood of survival without CLD . RESULTS Forty patients were enrolled at two centers . Birth weight and gestation were similar for treatment and placebo groups : 732 + /- 135 g versus 770 + /- 135 g and 25.2 + /- 1.3 weeks versus 25.4 + /- 1.5 weeks . More infants treated with hydrocortisone achieved study success , defined as survival without supplemental oxygen at 36 weeks ' postconception ( 12/20 [ 60 % ] vs 7/20 [ 35 % ] ) . Lower birth weight , histologic chorioamnionitis , and preeclampsia were significant risk factors , whereas study center , prenatal steroids , sex , and ethnicity were not significant . Hydrocortisone treatment decreased days on > 40 % oxygen , days on > 25 % oxygen , days on ventilator , and oxygen at discharge . Among infants exposed to chorioamnionitis , hydrocortisone treatment also was associated with increased enteral intake during the first month of life and with increased weight at 36 weeks ' postconception . Five treated infants and 6 placebo infants developed sepsis ; 3 in each group died . CONCLUSIONS First , early treatment with low-dose hydrocortisone in this population of extremely low birth weight infants increased the likelihood of survival without CLD . Second , the benefit was particularly apparent in infants with chorioamnionitis . Third , a larger multicenter trial is needed to verify the primary outcome and to better evaluate risks and benefits The objective of this study in premature infants was to assess the relationship between dexamethasone , growth and bone mineral accretion . Nine appropriate size for gestational age premature infants treated for chronic lung disease with tapering doses of dexamethasone ( 0.5 - 0.1 mg/kg/day over 37 + /- 7 days ) were individually matched to a comparison infant by sex , gestational age , birth-weight , and type of feed . Infant growth and bone mineral accretion were measured at equivalent gestational ages from recruitment until 6 months corrected age . During hospitalization , mean rate of weight , length and head circumference growth and bone mineral accretion in the distal radius were significantly lower in the dexamethasone-treated infants in spite of similar nutrient intakes . Dexamethasone infants had significantly lower plasma phosphorus , and urinary calcium , pyridinoline and N-telopeptide excretion . Dexamethasone affected absolute length , but not weight , throughout the study . No significant differences were observed in body composition or absolute radial and whole body bone mineral content . The results indicate that dexamethasone therapy compromises growth and bone mineral accretion in small premature infants . ' Catch-up ' linear growth was not evident at 6 months of age and reflects the importance of early nutrition interventions Eighteen infants were entered into a r and omized , placebo-controlled trial of dexamethasone therapy for chronic lung disease . Initial ventilation requirements were similar in the two groups , although all infants were in headbox oxygen on entry to the trial . The dexamethasone-treated infants showed a significantly more rapid improvement during the 1st week of treatment , although the overall duration of oxygen therapy was similar in both groups . Cranial ultrasound examination revealed new periventricular abnormalities in three out of the five dexamethasone-treated infants who had previously normal scans , compared with none of four similar placebotreated infants . A large trial , focussing on potential complications , is now needed We evaluated the use of dexamethasone in preterm infants to decrease morbidity associated with bronchopulmonary dysplasia in a r and omized , double-blind , placebo-controlled trial . Thirty-six preterm infants ( birth weight , less than or equal to 1250 g and gestational age , less than or equal to 30 weeks ) who were dependent on oxygen and mechanical ventilation at two weeks of age received a 42-day course of dexamethasone ( n = 13 ) , an 18-day course of dexamethasone ( n = 12 ) , or saline placebo ( n = 11 ) . The starting dose of dexamethasone was 0.5 mg per kilogram of body weight per day , and it was progressively lowered during the period of administration . Infants in the 42-day dexamethasone group , but not those in the 18-day group , were weaned from mechanical ventilation significantly faster than control infants ( medians 29 , 73 , and 84 days , respectively ; P less than 0.05 ) , and from supplemental oxygen ( medians 65 , 190 , and 136 days , respectively ; P less than 0.05 ) . No clinical complications of steroid administration were noted . Follow-up of all 23 survivors at 6 and 15 months of age showed good outcome ( normal neurologic examinations and Bayley Developmental Indexes greater than or equal to 84 ) in 7 of the 9 infants in the 42-day dexamethasone group , but in only 2 of the 9 infants in the 18-day dexamethasone group and 2 of the 5 in the placebo group ( P less than 0.05 ) . We conclude that dexamethasone therapy for 42 days improves pulmonary and neurodevelopmental outcome in very-low-birth-weight infants at high risk for bronchopulmonary dysplasia Objective . Ventilator-dependent preterm infants are often treated with a prolonged tapering course of dexamethasone to decrease the risk and severity of chronic lung disease . The objective of this study was to assess the effect of this therapy on developmental outcome at 1 year of age . Methods . Study participants were 118 very low birth weight infants who , at 15 to 25 days of life , were not weaning from assisted ventilation and were then enrolled in a r and omized , placebo-controlled , double-blind trial of a 42-day tapering course of dexamethasone . Infants were examined at 1 year of age , adjusted for prematurity , by a pediatrician and a child psychologist . A physical and neurologic examination was performed , and the Bayley Scales of Infant Development were administered . All examiners were blind to treatment group . Results . Groups were similar in terms of birth weight , gestational age , gender , and race . A higher percentage of dexamethasone recipients had major intracranial abnormalities diagnosed by ultrasonography ( 21 % vs 11 % ) . Group differences were not found for Bayley Mental Development Index ( median [ range ] for dexamethasone-treated group , 94 [ 50–123 ] ; for placebo group , 90 [ 28–117 ] ) or Psychomotor Development Index Index ( median [ range ] ) for dexamethasone-treated group , 78 ( 50–109 ) ; for placebo-treated group , 81 [ 28–117 ] ) . More dexamethasone-treated infants had cerebral palsy ( 25 % vs 7 % ) and abnormal neurologic examination findings ( 45 % vs 16 % ) . In stratified analyses , adjusted for major cranial ultrasound abnormalities , these associations persisted ( OR values for cerebral palsy , 5.3 ; 95 % CI : 1.3–21.4 ; OR values for neurologic abnormality 3.6 ; 95 % CI : 1.2–11.0 ) . Conclusions . A 42-day tapering course of dexamethasone was associated with an increased risk of cerebral palsy . Possible explanations include an adverse effect of this therapy on brain development and /or improved survival of infants who either already have neurologic injury or who are at increased risk for such injury OBJECTIVE : To study the effect of early postnatal dexamethasone ( days 1 - 3 ) on the incidence and severity of chronic lung disease in preterm infants with respiratory distress syndrome . METHODS : A multicentre , r and omised , placebo controlled , blinded study was carried out in 18 neonatal intensive care units in Israel . The primary outcome measure was survival to discharge without requirement for supplemental oxygen therapy beyond 28 days of life . The secondary outcome measures were requirement for mechanical ventilation at 3 and 7 days , duration of ventilation or oxygen therapy , need for subsequent steroids for established chronic lung disease and incidence of major morbidities . RESULTS : The study consisted of 248 infants ( dexamethasone n = 132 ; placebo n = 116 ) . No differences were found in the outcome variables except for a reduction in requirement for mechanical ventilation at age 3 days in treated infants ( dexamethasone 44 % , placebo 67 % ; P = 0.001 ) . Gastrointestinal haemorrhage , hypertension , and hyperglycaemia were more common in treated infants , but no life threatening complications , such as gastrointestinal perforation , were encountered . CONCLUSIONS : These data do no support the routine use of early postnatal steroids , but may justify further study in a selected , high risk group of infants |
12,831 | 22,084,455 | Oxycodone , hydromorphone , and morphine can be tried in patients who have not responded to weaker opioids .
For by far most patients , the optimal dose will be well below a 200-mg morphine equivalent dose per day . | OBJECTIVE To provide family physicians with a practical clinical summary of the Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain , developed by the National Opioid Use Guideline Group .
Weak opioids ( codeine and tramadol ) are recommended for mild to moderate pain that has not responded to first-line treatments . | & NA ; Comprised mainly of depression , anxiety , and high neuroticism , psychopathology diminishes the effectiveness of many chronic pain treatments . But , it is not known if it is associated with diminished opioid analgesia in patients with chronic , noncancer pain . We tested the hypothesis that psychopathology diminishes opioid analgesia in patients with discogenic low back pain in 60 patients not on opioids in a double blind , placebo controlled , r and om crossover design ed trial . Patients were stratified into three groups of psychological symptom severity ( LOW , MOD , and HIGH ) , based on composite scores on depression , anxiety for pain , and neuroticism scales . Subjects were given intravenous morphine ( 4–6 mg dosed by ideal body weight ) and placebo in r and om order on separate visits , and completed serial pain ratings over three hours at each session . With 20 subjects per group , there were nonsignificant differences between groups in the distribution of age , gender , baseline pain ( avg . 6.1/10 ) , radicular pain , and morphine dose ( 5.0 mg ) . For morphine analgesia , using a total pain relief calculation ( TOTPAR ) , the LOW group had 65.1 % TOTPAR vs. 41.0 % in the HIGH group , P=.026 . For placebo analgesia the LOW group had 7.7 % TOTPAR vs. 23.5 % in the HIGH group , P=.03 . A morphine minus placebo analgesia calculation revealed 59.2 % TOTPAR in the LOW group vs. 21.7 % in the HIGH group , P=.0001 . High levels of psychopathology are associated with diminished opioid analgesia in patients with discogenic low back pain . These results have implication s for the prescription of oral opioids to patients with chronic low back pain and psychopathology Background : Suicide among seniors is a significant health problem in north America , particularly for men in whom the rates rise steadily after 50 years of age . The goal of this study was to examine elder suicides identified from a large population -based data base using case – control methods to determine disease and medication factors related to suicide . Methods : A population -based 1 : 5 case – control study was conducted comparing seniors aged 66 years and older who had died by suicide with age and sex-matched controls . Case data were obtained through British Columbia ( BC ) Vital Statistics , whereas controls were r and omly selected from the BC Health Insurance Registry . Cases and controls were linked to the provincial PharmaCare data base to determine medication use and the provincial Physician Cl aims and Inpatient Hospitalization data bases to determine co-morbidity . Results : Between 1993 and 2002 a total of 602 seniors died by suicide in BC giving an annual rate of 13.2 per 100 000 . Firearms were the most common mechanism ( 28 % ) , followed by hanging/suffocation ( 25 % ) , self-poisoning ( 21 % ) , and jumping from height ( 7 % ) . In the adjusted logistic model , variables related to suicide included : lower socioeconomic status , depression/psychosis , neurosis , stroke , cancer , liver disease , parasuicide , benzodiazepine use , narcotic pain killer use and diuretic use . There was an elevated risk for those prescribed inappropriate benzodiazepines and for those using strong narcotic pain killers . Conclusion : This study is consistent with previous studies that have identified a relationship between medical or psychiatric co-morbidity and suicide in seniors . In addition , new and potentially useful information confirms that certain types and dosages of benzodiazepines are harmful to seniors and their use should be avoided OBJECTIVE To assess the prevalence , treatment and impact of chronic pain in Canada . METHODS A stratified r and om sample of 2012 adult Canadians ( weighted by sex , age and region according to 1996 census data ) was surveyed by telephone in 2001 to determine the prevalence of chronic pain , defined as continuous or intermittent pain for at least six months . A second sample of 340 chronic pain sufferers who were taking prescription medication for their pain was studied in detail to determine current therapeutic approaches and to assess the social and economic impact of chronic pain . RESULTS Chronic noncancer pain was reported by 29 % of the respondents , with increased frequency in women and older age groups . The average duration of pain was 10.7 years and the average intensity was 6.3 ( on a scale from 1 to 10 ) , with 80 % reporting moderate or severe pain . Anti-inflammatory agents were prescribed for 49 % of respondents and opioid analgesics were prescribed for 22 % ( two-thirds of these were codeine ) . Almost 70 % were worried about addiction potential , and one-third felt that strong analgesics should be reserved for terminal illnesses . Almost one-half were unable to attend social and family events , and the mean number of days absent from work in the past year due to chronic pain was 9.3 . INTERPRETATION Chronic noncancer pain is common in Canadian adults and has a major social and economic impact . Despite growing evidence supporting the efficacy and safety of major opioid analgesics for chronic noncancer pain , less than 10 % of chronic pain patients taking prescription medication were treated with a major opioid . Chronic pain is undertreated in Canada , and major opioid analgesics are probably underutilized in the management of moderate to severe pain as part of a multidisciplinary treatment program & NA ; Chronic pain patients who show aberrant drug‐related behavior often are discontinued from treatment when they are noncompliant with their use of opioids for pain . The purpose of this study was to conduct a r and omized trial in patients who were prescribed opioids for noncancer back pain and who showed risk potential for or demonstration of opioid misuse to see if close monitoring and cognitive behavioral substance misuse counseling could increase overall compliance with opioids . Forty‐two patients meeting criteria for high‐risk for opioid misuse were r and omized to either st and ard control ( High‐Risk Control ; N = 21 ) or experimental compliance treatment consisting of monthly urine screens , compliance checklists , and individual and group motivational counseling ( High‐Risk Experimental ; N = 21 ) . Twenty patients who met criteria indicating low potential for misuse were recruited to a low‐risk control group ( Low‐Risk Control ) . Patients were followed for 6 months and completed pre‐ and post‐ study question naires and monthly electronic diaries . Outcomes consisted of the percent with a positive Drug Misuse Index ( DMI ) , which was a composite score of self‐reported drug misuse ( Prescription Drug Use Question naire ) , physician‐reported abuse behavior ( Addiction Behavior Checklist ) , and abnormal urine toxicology results . Significant differences were found between groups with 73.7 % of the High‐Risk Control patients demonstrating positive scores on the DMI compared with 26.3 % from the High‐Risk Experimental group and 25.0 % from the Low‐Risk Controls ( p < 0.05 ) . The results of this study demonstrate support for the benefits of a brief behavioral intervention in the management of opioid compliance among chronic back pain patient at high‐risk for prescription opioid misuse Abstract Use of opioids for chronic non‐cancer pain is controversial and the efficacy of comprehensive pain rehabilitation programs ( CPRPs ) that incorporate opioid withdrawal requires further investigation . We test the hypothesis that patients with chronic pain and longst and ing opioid use who undergo opioid withdrawal in the course of rehabilitative treatment will experience significant and sustained improvement in pain and functioning similar to patients who were not taking opioids . A longitudinal design study compared 373 consecutive patients admitted to the Mayo Clinic Pain Rehabilitation Center at admission , discharge and six‐month posttreatment by opioid status at admission . Measures of pain severity , depression , psychosocial functioning , health status , and pain catastrophizing were used to assess between‐ and within‐group differences . Treatment involved a 3‐week interdisciplinary pain rehabilitation program focused on functional restoration . Over one‐half of patients ( 57.1 % ) were taking opioids daily at admission . The majority of patients ( 91 % ) completed rehabilitation and 70 % of patients who completed the program returned question naires six months posttreatment . On admission , patients taking low‐ and high‐dose opioids reported significantly greater pain severity ( P = .001 ) and depression ( P = .001 ) than the non‐opioid group . Significant improvement was found on all outcome variables following treatment ( P < .001 ) and six‐month posttreatment ( P < .001 ) regardless of opioid status at admission . There were no differences between the opioid and non‐opioid groups upon discharge from the program or at six months following treatment . Conclusion : Patients with longst and ing CPRP on chronic opioid therapy , who choose to participate in interdisciplinary rehabilitation that incorporates opioid withdrawal , can experience significant and sustained improvement in pain severity and functioning BACKGROUND Opioids are used extensively for chronic pain management in the United States . The frequency of opioid use prior to presenting to interventional pain management setting s and in interventional pain management setting s has been shown to be above 90 % . Given that controlled substance abuse and illicit drug use are prevalent phenomena , adherence monitoring of patients that are prescribed opioids is becoming common . Adherence monitoring is carried out by an appropriate history , periodic evaluation of appropriate intake of drugs , r and om drug testing , and pill counts . Crucial to adherence monitoring is an initial controlled substance agreement and repeated review of the terms of this agreement with on-going education . However , the effect of adherence monitoring on drug abuse is unclear . OBJECTIVE To identify controlled substance abuse through implementation of the terms of a controlled substance agreement , including periodic review and monitoring outside the organization . STUDY DESIGN Prospect i ve evaluation with historical controls . METHODS Five hundred consecutive patients receiving prescription controlled substances were followed in a prospect i ve manner . The evaluation consisted of a chart review to monitor controlled substance intake , with special attention to drugs obtained from outside the organization . Data collection for this purpose included information from records , pharmacies , referring physicians , and all the physicians involved in the treatment of the patient . RESULTS Results from 500 consecutive patients were evaluated . Controlled substance abuse was seen in 9 % of patients ; overall , 5 % of patients were obtaining controlled substances from other physicians , and 4 % from illegal sources . CONCLUSION Adherence monitoring , including controlled substance agreements and various periodic measures of compliance was associated with a 50 % reduction in opioid abuse Objective : Depression and anxiety are common in sickle cell disease ( SCD ) but relatively little is known about their impact on SCD adults . This study measured prevalence of depression and anxiety in SCD adults , and their effects on crisis and noncrisis pain , quality -of-life , opioid usage , and healthcare utilization . Methods : The Pain in Sickle Cell Epidemiology Study is a prospect i ve cohort study in 308 SCD adults . Baseline variables included demographics , genotype , laboratory data , health-related quality -of-life , depression , and anxiety . Subjects completed daily diaries for up to 6 months , reporting sickle cell pain intensity , distress , interference , whether they were in a sickle cell crisis , as well as health care and opioid utilization . Results : Two hundred thirty-two subjects who completed at least 1 month of diaries were studied ; 27.6 % were depressed and 6.5 % had any anxiety disorder . Depressed subjects had pain on significantly more days than nondepressed subjects ( mean pain days 71.1 % versus 49.6 % , p < .001 ) . When in pain on noncrisis days , depressed subjects had higher mean pain , distress from pain , and interference from pain . Both depressed and anxious subjects had poorer functioning on all eight SF-36 subscales , even after controlling for demographics , hemoglobin type , and pain . The anxious subjects had more pain , distress from pain , and interference from pain , both on noncrisis pain days and on crisis days , and used opioids more often . Conclusions : Depression and anxiety predicted more daily pain and poorer physical and mental quality -of-life in adults with SCD , and accounted for more of the variance in all domains of quality -of-life than hemoglobin type . SCD = sickle cell disease ; PiSCES = Pain in Sickle Cell Epidemiology Study ; ED = emergency department ; PHQ = patient health question naire ; MOS SF-36 = Medical Outcome Study 36 item Short Form-36 ; MMSE = mini mental status examination BACKGROUND Prescription drug abuse and illicit drug use are common in chronic pain patients . Adherence monitoring with screening tests , and urine drug testing , periodic monitoring with prescription monitoring programs , has become a common practice in recent years . R and om drug testing for appropriate use of opioids and use of illicit drugs is often used in pain management practice s. Thus , it is expected that r and om urine drug testing will deter use of illicit drugs , and also improve compliance . OBJECTIVES To study the prevalence of illicit drug use in patients receiving opioids for chronic pain management and to compare the results of illicit drug use with the results from a previous study . DESIGN A prospect i ve , consecutive study . SETTING Interventional pain management practice setting in the United States . METHODS A total of 500 consecutive patients on opioids , considered to be receiving stable doses of opioids supplemental to their interventional techniques , were studied by r and om drug testing . Testing was performed by rapid drug screen . Results were considered positive if one or more of the monitored illicit drugs including cocaine , marijuana ( THC ) , methamphetamine or amphetamines were present . RESULTS Illicit drug use was evident in 80 patients , or 16 % , with marijuana in 11 % , cocaine in 5 % , and methamphetamine and /or amphetamines in 2 % . When compared with previous data , the overall illicit drug use was significantly less . Illicit drug use in elderly patients was absent . CONCLUSION The prevalence of illicit drug abuse in patients with chronic pain receiving opioids continues to be a common occurence . This study showed significant reductions in overall illicit drug use with adherence monitoring combined with r and om urine drug testing OBJECTIVE To measure the impact of a structured opioid renewal program for chronic pain run by a nurse practitioner ( NP ) and clinical pharmacist in a primary care setting . PATIENTS AND SETTING Patients with chronic noncancer pain managed with opioid therapy in a primary care clinic staffed by 19 providers serving 50,000 patients at an urban academic Veterans hospital . DESIGN Naturalistic prospect i ve outcome study . INTERVENTION Based on published opioid prescribing guidelines and focus groups with primary care providers ( PCPs ) , a structured program , the Opioid Renewal Clinic ( ORC ) , was design ed to support PCPs managing patients with chronic noncancer pain requiring opioids . After training in the use of opioid treatment agreements ( OTAs ) and r and om urine drug testing ( UDT ) , PCPs worked with a pharmacist-run prescription management clinic supported by an onsite pain NP who was backed by a multi-specialty Pain Team . After 2 years , the program was evaluated for its impact on PCP practice and satisfaction , patient adherence , and pharmacy cost . RESULTS A total of 335 patients were referred to the ORC . Of the 171 ( 51 % ) with documented aberrant behaviors , 77 ( 45 % ) adhered to the OTA and resolved their aberrant behaviors , 65 ( 38 % ) self-discharged , 22 ( 13 % ) were referred for addiction treatment , and seven ( 4 % ) with consistently negative UDT were weaned from opioids . The 164 ( 49 % ) who were referred for complexity including history of substance abuse or need for opioid rotation or titration , with no documented aberrant drug-related behaviors , continued to adhere to the OTA . Use of UDT and OTAs by PCPs increased . Significant pharmacy cost savings were demonstrated . CONCLUSION An NP/ clinical pharmacist-run clinic , supported by a multi-specialty team , can successfully support a primary care practice in managing opioids in complex chronic pain patients AIMS To investigate the extent of concomitant use of analgesic and psychotropic medicines among home-dwelling elderly people aged at least 75 years in Finl and . METHODS This was a population -based study in Finl and , performed as part of Kuopio 75 + study focusing on the clinical epidemiology of diseases , medication and functional capacity . A r and om sample of 700 persons was drawn from the total population of the city of Kuopio , eastern Finl and , aged 75 years on January 1 , 1998 ( n = 4518 ) . Ninety-nine persons could not be examined and 78 were living in long-term institutions , so that the number of home-dwelling elderly persons amounted to 523 . A trained nurse interviewed the participants about their use of medicines , and a geriatrician examined their overall physical and mental status . Dementia and depression were diagnosed according to the DSM IV criteria . Both regular and irregular prescribed and nonprescribed drug use was recorded . RESULTS Every fourth elderly person ( 27.2 % ) used analgesics and psychotropics concomitantly , this use becoming twice as common with advancing age ( 19.6 % in the age group 75 - 79 years , 38.2 % among the oldest , aged 85 + years ) . Concomitant use of psychotropics and opioids also became more common with increasing age ( 2.8 % in age group 75 - 79 years and 9.6 % in the oldest group , aged 85 + years ) . The use of opioids was nearly twice as common among concomitant users ( 19.7 % ) than among those using only analgesics ( 11.3 % ) . Concomitant users suffered from interfering daily pain and daily pain at rest more commonly than nonusers of analgesics . Depression , sleeping problems and polypharmacy were more common among the concomitant users , who had also had more hip fractures than the rest . CONCLUSIONS Concomitant use of analgesics and psychotropics becomes more common with advancing age and is a potential risk factor for adverse drug effects OBJECTIVES To study the effect of morphine and opiates on fracture risk . DESIGN Case-control study . SETTING Nationwide register-based study . SUBJECTS Cases were all subjects with any fracture sustained during the year 2000 ( n = 124,655 ) . For each case , three controls ( n = 373,962 ) matched on age and gender were r and omly drawn from the background population . The primary exposure variables were use of morphine and opiates . Morphine and other opiates had been used by 10 015 ( 8.0 % ) of the case subjects and 12 108 ( 3.2 % ) of the controls . Adjustments were made for several confounders including prior fracture , and use of weak analgesics [ nonsteroidal anti-inflammatory drugs , acetylsalicylic acid ( ASA ) and acetaminophene ] . The effect of dose was examined by stratifying for cumulated dose ( defined daily dose ) . MAIN OUTCOME MEASURE Fracture . RESULTS Morphine ( 1.47 , 95 % CI 1.37 - 1.58 ) , fentanyl ( 2.23 , 95 % CI 1.89 - 2.64 ) , methadone ( 1.39 , 95 % CI 1.05 - 1.83 ) , oxycodone ( 1.36 , 95 % CI 1.08 - 1.69 ) , nicomorphine ( 1.57 , 95 % CI 1.38 - 1.78 ) , ketobemidone ( 1.07 , 95 % CI 1.02 - 1.13 ) , tramadol ( 1.54 , 95 % CI 1.49 - 1.58 ) and codeine ( 1.16 , 95 % CI 1.12 - 1.20 ) were all associated with an increase in overall fracture risk . No increase was present for buprenorphine ( 0.86 , 95 % CI 0.79 - 0.95 ) , pethidine ( 0.98 , 95 % CI 0.89 - 1.08 ) , dextropropoxiphene ( 1.02 , 95 % CI 0.90 - 1.16 ) , and combinations of ASA and codeine ( 0.94 , 95 % CI 0.88 - 1.01 ) . CONCLUSIONS An increased fracture risk is seen in users of morphine and opiates . The reason for this may be related to the risk of falls due to central nervous system effects such as dizziness OBJECTIVE To provide clinicians with a brief screening tool to predict accurately which individuals may develop aberrant behaviors when prescribed opioids for chronic pain . DESIGN One hundred and eighty-five consecutive new patients treated in one pain clinic took the self-administered Opioid Risk Tool ( ORT ) . The ORT measured the following risk factors associated in scientific literature with substance abuse : personal and family history of substance abuse ; age ; history of preadolescent sexual abuse ; and certain psychological diseases . Patients received scores of 0 - 3 ( low risk ) , 4 - 7 ( moderate risk ) , or > or= 8 ( high risk ) , indicating the probability of their displaying opioid-related aberrant behaviors . All patients were monitored for aberrant behaviors for 12 months after their initial visits . RESULTS For those patients with a risk category of low , 17 out of 18 ( 94.4 % ) did not display an aberrant behavior . For those patients with a risk category of high , 40 out of 44 ( 90.9 % ) did display an aberrant behavior . The authors used the c statistic to vali date the ORT , because it simultaneously assesses sensitivity and specificity . The ORT displayed excellent discrimination for both the male ( c = 0.82 ) and the female ( c = 0.85 ) prognostic models . CONCLUSION In a preliminary study , among patients prescribed opioids for chronic pain , the ORT exhibited a high degree of sensitivity and specificity for determining which individuals are at risk for opioid-related , aberrant behaviors . Further studies in a variety of pain and nonpain setting s are needed to determine the ORT 's universal applicability AIM To report results on the prospect i ve follow-up of 34 pregnant women exposed to buprenorphine maintenance for opiate dependence . DESIGN AND SETTING Prospect i ve multicentre study : all pregnant women receiving buprenorphine as maintenance therapy were included as early as possible during their pregnancy . PARTICIPANTS The pregnant women were recruited from opiate maintenance therapy centres , general practitioner-networks involved in addiction , maternity hospitals and centres for drug information during pregnancy . MEASUREMENTS Women : drugs and medications consumed , medical and obstetrical events ; offspring : withdrawal syndrome , malformation , neonatal disease . FINDINGS The buprenorphine-exposed pregnancies result ed in 31 live births , one stillbirth , one spontaneous abortion and one voluntary termination . A neonatal withdrawal syndrome was observed in 13 cases ( 41.9 % ) and eight of these babies required opiate treatment . Two neonates had a malformation : a premature ductus arteriosus stricture and a tragus appendix . CONCLUSION Taken together with other prospect i ve studies , no alarming results were observed concerning pregnancy outcomes . However , further data from the comparative prospect i ve study are required to determine whether buprenorphine can be considered as a good alternative to methadone treatment in pregnant women BACKGROUND Use of opioids for chronic noncancer pain is increasing , but st and ards of care for this practice are poorly defined . Psychiatric disorders are associated with increased physical symptoms such as pain and may be associated with opioid use , but no prospect i ve population -based studies have addressed this issue . METHODS Analysis of longitudinal data from 6439 participants in the 1998 and 2001 waves of Healthcare for Communities , a nationally representative telephone community survey . RESULTS Two hundred thirty-seven subjects ( 3.6 % ) reported regular prescription opioid use in 2001 . In unadjusted logistic regression models , respondents with a common mental health disorder in 1998 ( 1165 [ 12.6 % ] ; major depression , dysthymia , generalized anxiety disorder , or panic disorder ) were more likely to report opioid use in 2001 than those without any of these disorders ( odds ratio [ OR ] , 4.43 ; 95 % confidence interval [ CI ] , 3.64 - 5.38 ; P<.001 ) . Risk was increased for initiation ( OR , 3.26 ; 95 % CI , 2.44 - 4.34 ; P<.001 ) and continuation ( OR , 2.30 ; 95 % CI , 1.02 - 5.17 ; P = .04 ) of opioids . Respondents reporting problem drug use ( 136 [ 2.0 % ] ; OR , 3.57 ; 95 % CI , 2.32 - 5.50 ; P<.001 ) but not problem alcohol use ( 401 [ 6.5 % ] ; OR , 0.73 ; 95 % CI , 0.43 - 1.24 ; P = .25 ) reported higher rates of prescribed opioid use than those without problem use . In multivariate logistic regression models controlling for 1998 demographic and clinical variables , common mental health disorder ( OR , 1.96 ; 95 % CI , 1.47 - 2.62 ; P<.001 ) and problem drug use ( OR , 2.98 ; 95 % CI , 1.68 - 5.30 ; P<.001 ) remained significant predictors of opioid use in 2001 . CONCLUSIONS Common mental health disorders and problem drug use are associated with initiation and use of prescribed opioids in the general population . Attention to psychiatric disorders is important when considering opioid therapy Rationale The subjective , psychomotor , and physiological effects of a widely prescribed and abused prescription opioid , oxycodone , have not been studied in a population of non-drug-abusing people . Objectives To characterize the effects of oxycodone in non-drug-abusing volunteers . Methods Eighteen volunteers participated in a crossover , r and omized , double-blind study in which they received , all p.o . , placebo , 10 mg oxycodone , 20 mg oxycodone , 30 mg oxycodone , 40 mg morphine , and 2 mg lorazepam . Measures were assessed before and for 300 min after drug administration . End-of-session and 24-h post-session measures were taken to assess residual drug effects and overall subjects ' assessment s of the drug effects . Results Subjective effects of oxycodone were dose related , with the majority of statistically significant effects limited to the two higher doses tested . Oxycodone produced a profile of subjective effects that included both pleasant and unpleasant effects . Morphine in general produced effects similar in magnitude to those of 10 mg and 20 mg oxycodone . Peak liking and drug-wanting ratings were increased by all doses of oxycodone and by morphine , and trough ratings of liking ( dislike ) were lower in the 20-mg and 30-mg oxycodone conditions , relative to the placebo condition . Post-session ratings of overall liking and drug wanting were not statistically significant , either at the end of the session or 24 h later . Cognitive and psychomotor impairment were obtained with the higher doses of oxycodone , but to a much lesser degree than that of lorazepam . Miosis and exophoria were increased in a dose-related manner by oxycodone . Conclusions Oxycodone produced effects similar to those of other mu opioid agonists . Although oxycodone produced abuse liability-related subjective effects , it also produced unpleasant effects , a phenomenon we have observed in other opioid studies in non-drug-abusing volunteers |
12,832 | 27,889,444 | Conclusions : The analysis of existing studies showed that a series of 4–10 EFT sessions is an efficacious treatment for PTSD with a variety of population s. The studies examined reported no adverse effects from EFT interventions and showed that it can be used both on a self‐help basis and as a primary evidence ‐based treatment for PTSD | Background : Over the past two decades , growing numbers of clinicians have been utilizing emotional freedom techniques ( EFT ) in the treatment of posttraumatic stress disorder ( PTSD ) , anxiety , and depression .
R and omized controlled trials ( RCTs ) have shown encouraging outcomes for all three conditions .
Objective : To assess the efficacy of EFT in treating PTSD by conducting a meta‐ analysis of existing RCTs . | OBJECTIVE Advocates of new therapies frequently make bold cl aims regarding therapeutic effectiveness , particularly in response to disorders which have been traditionally treatment-refractory . This paper review s a collection of new therapies collectively self-termed " The Power Therapies " , outlining their proposed procedures and the evidence for and against their use . These therapies are then put to the test for pseudoscientific practice . METHOD Therapies were included which self-describe themselves as " Power Therapies " . Published work search es were conducted on each therapy using Medline and PsychInfo data bases for r and omized controlled trials assessing their efficacy , except for the case of Eye Movement Desensitization and Reprocessing ( EMDR ) . Eye Movement Desensitization and Reprocessing has more r and omized controlled studies conducted on its efficacy than any other treatment for trauma and thus , previous meta-analyses were evaluated . RESULTS AND CONCLUSIONS It is concluded that these new therapies have offered no new scientifically valid theories of action , show only non-specific efficacy , show no evidence that they offer substantive improvements to extant psychiatric care , yet display many characteristics consistent with pseudoscience Male veterans and their spouses ( N = 218 ) attending one of six-week-long retreats were assessed for posttraumatic stress disorder ( PTSD ) symptoms pre- and postintervention . Participants were evaluated using the PTSD checklist ( PCL ) , on which , a score of > 49 indicates clinical symptom levels . The mean pretest score was 61.1 ( SD ± 12.5 ) for veterans and 42.6 ( SD ± 16.5 ) for spouses ; 83 % of veterans and 29 % of spouses met clinical criteria . The multimodal intervention used Emotional Freedom Techniques and other energy psychology ( EP ) methods to address PTSD symptoms and a variety of complementary and alternative medicine ( CAM ) modalities for stress reduction and re source building . Interventions were delivered in group format as well as individual counseling sessions . Data were analyzed for each retreat , as well as for the six retreats as a whole . Mean post-test PCL scores decreased to 41.8 ( SE ± 1.2 ; p < .001 ) for veterans , with 28 % still clinical . Spouses demonstrated substantial symptom reductions ( M = 28.7 , SE ± 1.0 ; p < .001 ) , with 4 % still clinical . A follow-up assessment ( n = 63 ) found PTSD symptom levels dropping even further for spouses ( p < .003 ) , whereas gains were maintained for veterans . The significant reduction in PTSD symptoms is consistent with other published reports of EP treatment , though counter to the usual long-term course of the condition . The results indicate that a multimodal CAM intervention incorporating EP may offer benefits to family members as well as veterans suffering from PTSD symptoms . Recommendations are made for further research to answer the questions posed by this study A r and omized controlled trial of veterans with clinical levels of PTSD symptoms found significant improvements after Emotional Freedom Techniques ( EFT ) . Although pain , depression , and anxiety were not the primary targets of treatment , significant improvements in these conditions were noted . Subjects ( N = 59 ) received six sessions of EFT coaching supplementary to primary care . They were assessed using the SA-45 , which measures nine mental health symptom domains and also has two general scales measuring the breadth and depth of psychological distress . Anxiety and depression both reduced significantly , as did the breadth and depth of psychological symptoms . Pain decreased significantly during the intervention period ( -41 % , p < .0001 ) . Subjects were followed up at three and six months , revealing significant relationships between PTSD , depression , and anxiety at several assessment points . At follow-up , pain remained significantly lower than at pretest . The results of this study are consistent with other reports showing that , as PTSD symptoms are reduced , general mental health improves , and pain levels drop . The ability of EFT to produce reliable and long-term gains after relatively brief interventions indicates its utility in reducing the estimated trillion-dollar cost of treating veteran mental health disorders in the coming years Prior research indicates elevated but sub clinical posttraumatic stress disorder ( PTSD ) symptoms as a risk factor for a later diagnosis of PTSD . This study examined the progression of symptoms in 21 sub clinical veterans . Participants were r and omized into a treatment as usual ( TAU ) wait-list group and an experimental group , which received TAU plus six sessions of clinical emotional freedom techniques ( EFT ) . Symptoms were assessed using the PCL-M ( Posttraumatic Checklist-Military ) on which a score of 35 or higher indicates increased risk for PTSD . The mean pretreatment score of participants was 39 ± 8.7 , with no significant difference between groups . No change was found in the TAU group during the wait period . Afterward , the TAU group received an identical clinical EFT protocol . Posttreatment groups were combined for analysis . Scores declined to a mean of 25 ( -64 % , P < .0001 ) . Participants maintained their gains , with mean three-month and six-month follow-up PCL-M scores of 27 ( P < .0001 ) . Similar reductions were noted in the depth and breadth of psychological conditions such as anxiety . A Cohen 's d = 1.99 indicates a large treatment effect . Reductions in traumatic brain injury symptoms ( P = .045 ) and insomnia ( P = .004 ) were also noted . Symptom improvements were similar to those assessed in studies of PTSD-positive veterans . EFT may thus be protective against an increase in symptoms and a later PTSD diagnosis . As a simple and quickly learned self-help method , EFT may be a clinical ly useful element of a resiliency program for veterans and active-duty warriors The present study reports on the first ever controlled comparison between eye movement desensitization and reprocessing ( EMDR ) and emotional freedom techniques ( EFT ) for posttraumatic stress disorder . A total of 46 participants were r and omized to either EMDR ( n = 23 ) or EFT ( n = 23 ) . The participants were assessed at baseline and then reassessed after an 8-week waiting period . Two further blind assessment s were conducted at posttreatment and 3-months follow-up . Overall , the results indicated that both interventions produced significant therapeutic gains at posttreatment and follow-up in an equal number of sessions . Similar treatment effect sizes were observed in both treatment groups . Regarding clinical significant changes , a slightly higher proportion of patients in the EMDR group produced substantial clinical changes compared with the EFT group . Given the speculative nature of the theoretical basis of EFT , a dismantling study on the active ingredients of EFT should be subject to future research Abstract Brain processing of acupuncture stimuli in chronic neuropathic pain patients may underlie its beneficial effects . We used fMRI to evaluate verum and sham acupuncture stimulation at acupoint LI‐4 in Carpal Tunnel Syndrome ( CTS ) patients and healthy controls ( HC ) . CTS patients were retested after 5 weeks of acupuncture therapy . Thus , we investigated both the short‐term brain response to acupuncture stimulation , as well as the influence of longer‐term acupuncture therapy effects on this short‐term response . CTS patients responded to verum acupuncture with greater activation in the hypothalamus and deactivation in the amygdala as compared to HC , controlling for the non‐specific effects of sham acupuncture . A similar difference was found between CTS patients at baseline and after acupuncture therapy . For baseline CTS patients responding to verum acupuncture , functional connectivity was found between the hypothalamus and amygdala – the less deactivation in the amygdala , the greater the activation in the hypothalamus , and vice versa . Furthermore , hypothalamic response correlated positively with the degree of maladaptive cortical plasticity in CTS patients ( inter‐digit separation distance ) . This is the first evidence suggesting that chronic pain patients respond to acupuncture differently than HC , through a coordinated limbic network including the hypothalamus and amygdala Sixty veterans ( 54 men , 6 women ) with chronic military-related posttraumatic stress disorder ( PTSD ) participated in a wait-list controlled trial of cognitive processing therapy ( CPT ) . The overall dropout rate was 16.6 % ( 20 % from CPT , 13 % from waiting list ) . R and om regression analyses of the intention-to-treat sample revealed significant improvements in PTSD and comorbid symptoms in the CPT condition compared with the wait-list condition . Forty percent of the intention-to-treat sample receiving CPT did not meet criteria for a PTSD diagnosis , and 50 % had a reliable change in their PTSD symptoms at posttreatment assessment . There was no relationship between PTSD disability status and outcomes . This trial provides some of the most encouraging results of PTSD treatment for veterans with chronic PTSD and supports increased use of cognitive- behavioral treatments in this population Abstract This study examined the changes in cortisol levels and psychological distress symptoms of 83 non clinical subjects receiving a single hourlong intervention . Subjects were r and omly assigned to either an emotional freedom technique ( EFT ) group , a psychotherapy group receiving a supportive interviews ( SI ) , or a no treatment ( NT ) group . Salivary cortisol assays were performed immediately before and 30 minutes after the intervention . Psychological distress symptoms were assessed using the symptom assessment -45 . The EFT group showed statistically significant improvements in anxiety ( −58.34 % , p < 0.05 ) , depression ( −49.33 % , p < 0.002 ) , the overall severity of symptoms ( −50.5 % , p < 0.001 ) , and symptom breadth ( −41.93 % , p < 0.001 ) . The EFT group experienced a significant decrease in cortisol level ( −24.39 % ; SE , 2.62 ) compared with the decrease observed in the SI ( −14.25 % ; SE , 2.61 ) and NT ( −14.44 % ; SE , 2.67 ) groups ( p < 0.03 ) . The decrease in cortisol levels in the EFT group mirrored the observed improvement in psychological distress Purpose : To assess the feasibility of measuring changes in gene expression associated with post-traumatic stress disorder ( PTSD ) treatment using emotional freedom techniques ( EFT ) . Design : Participants were r and omized into an EFT group receiving EFT and treatment as usual ( TAU ) throughout a 10-week intervention period and a group receiving only TAU during the intervention period and then receiving EFT . Setting : A community clinic and a research institute in California . Participants : Sixteen veterans with clinical levels of PTSD symptoms . Intervention : Ten hour-long sessions of EFT . Measures : Messenger RNA levels for a focused panel of 93 genes related to PTSD . The Symptom Assessment 45 question naire , Hospital Anxiety and Depression Scale , Insomnia Severity Scale , SF-12v2 for physical impairments , and Rivermead Postconcussion Symptoms Question naire . Analysis : Pre- , posttreatment , and follow-up mean scores on question naires were assessed using repeated measures 1-way analysis of variance . A Student t test and post hoc analyses were performed on gene expression data . Results : Post-traumatic stress disorder symptoms declined significantly in the EFT group ( −53 % , P < .0001 ) . Participants maintained their gains on follow-up . Significant differential expression of 6 genes was found ( P < .05 ) when comparing the expression levels before and after the intervention period in participants receiving EFT . Conclusion : Study results identify c and i date gene expression correlates of successful PTSD treatment , providing guidelines for the design of further studies aim ed at exploring the epigenetic effects of EFT |
12,833 | 10,859,208 | There is some evidence that false-negative results may have a large legal impact .
For example , in cervical screening they have led to legal action and its associated costs , including payment of compensation ; this is based on reports of events in both the UK and US health systems .
False-negatives are evident in all screening programmes , even when the quality of the service provided is high .
They may have the potential to delay the detection of breast and cervical cancer , but there is little evidence to help assess their psychological consequences in these or other screening programmes . | BACKGROUND When assessing whether a screening programme is appropriate , there is a particular obligation to ensure that the harms as well as the benefits are considered .
Among these harms is the likelihood that false-negative results will occur .
In some cases , the consequences of these can be difficult to assess , although false reassurance leading to diagnostic delay and subsequent treatment has been suggested .
However , no test is totally accurate ( with 100 % sensitivity and specificity ) , and false-negative results are inherent in any screening programme that does not have 100 % sensitivity .
This review was carried out to assess the medical , psychological , economic and legal consequences of false-negative results that occur in national screening programmes .
OBJECTIVES ( 1 ) to determine the consequences of false-negative findings ; ( 2 ) to investigate how their adverse effects can be minimised ; to assess their implication s for the NHS , including the impact of false-negatives on public confidence in screening programmes ; to identify relevant theoretical perspectives that may be potentially useful when considering the implication s of false-negative results . | The Canadian National Breast Screening Study ( NBSS ) is a r and omized controlled trial to assess the effect of screening on breast cancer mortality . The NBSS design ated a single reference radiologist who blindly review ed over the course of the study 5200 r and omly selected two-view mammographic examinations of women not known to have breast cancer . He also review ed 575 screening-detected breast cancer ( SBC ) cases and 102 interval breast cancer ( IBC ) cases . All cancers were histologically proven . As a result of the review s , comments on inter-observer agreement , interpretation , and technical quality were conveyed on an ongoing basis to radiologists appointed to 15 NBSS screening centers . Agreement of the reference radiologist with center radiologists was better for breast cancer cases ( kappa = 0.511 , P less than .002 ) than for those not known to have breast cancer ( kappa = 0.307 , P less than .002 ) . Observer error and technical problems led to delayed detection in 22 % of SBCs and 35 % of IBCs . Another 11 % of SBCs and 58 % of IBCs were probably mammographically occult . No similarly comprehensive review of mammography during a screening program has been published . Suggestions arising from the NBSS review were sometimes resisted by center radiologists . Measures are suggested which might facilitate acceptance of recommendations arising from audit mechanisms in mammography screening programs , thereby enhancing opportunities for mammographic excellence OBJECTIVES : To estimate women 's expectations of the accuracy of screening mammography and to explore attitudes towards compensation for missed cancers . DESIGN : Cross sectional survey ( by telephone ) . SETTING : Australia ; population -based survey conducted in April 1996 . PARTICIPANTS : R and om sample of women aged 30 - 69 years . A total of 2935 women completed the Breast Health Survey ( adjusted response rate 65 % ) . A r and om sample of 115 completed this sub-survey on perceived sensitivity of mammographic screening and compensation for missed cancers . RESULTS : About one third of women ( 32.2 % , 95 % CI 23.7 , 40.7 ) had an unrealistically high expectation of the sensitivity of screening mammography , reporting it to be 95 % or higher . Approximately 40 % of the women ( 43.5 % , 95 % CI 34.4 , 52.6 ) thought that screening mammography should pick up all cancers ( should have a sensitivity of 100 % ) . Just under half the women ( 45.2 % , 95 % CI 36.1 , 54.3 ) said financial compensation should be awarded for a cancer missed by screening mammography even if the cancer was missed as a consequence of the small failure rate of the test . Younger women living in metropolitan areas and women who had realistic expectations of the accuracy of the tests were more likely to favour financial compensation . CONCLUSION : Unrealistically high expectations of the sensitivity of screening mammography were common in this group of women . Many women favoured financial compensation for missed cancers even if the cancer was missed solely because of the failure rate of the test . Public education is required to inform women of the limited sensitivity of breast cancer tests but this may not reduce cl aims for financial compensation when cancers are missed Expected utility theory is felt by its proponents to be a normative theory of decision making under uncertainty . The theory starts with some simple axioms that are held to be rules that any rational person would follow It can be shown that if one adheres to these axioms , a numerical quantity , generally referred to as utility , can be assigned to each possible outcome , with the preferred course of action being that which has the highest expected utility . One of these axioms , the independence principle , is controversial , and is frequently violated in experimental situations . Proponents of the theory hold that these violations are irrational The independence principle is simply an axiom dictating consistency among preferences , in that it dictates that a rational agent should hold a specified preference given another stated preference . When applied to preferences between lotteries , the independence principle can be demonstrated to be a rule that is followed only when preferences are formed in a particular way . The logic of expected utility theory is that this demonstration proves that preferences should be formed in this way An alternative interpretation is that this demonstrates that the independence principle is not a valid general rule of consistency , but in particular , is a rule that must be followed if one is to consistently apply the decision rule " choose the lottery that has the highest expected utility . " This decision rule must be justified on its own terms as a valid rule of rationality by demonstration that violation would lead to decisions that conflict with the decision maker 's goals This rule does not appear to be suitable for medical decisions because often these are one-time decisions in which expectation , a long-run property of a r and om variable , would not seem to be applicable . This is particularly true for those decisions involving a non-trivial risk of death Key words . expected utility theory , von Neumann-Morgenstern utility , strength of preference ; decision analysis ; independence principle . ( Med Decis Making 1996;16:1 - 6 The effectiveness and costs of prenatal screening programmes for Down 's syndrome using maternal serum markers will vary significantly depending on the biological cut-off values chosen in order to select women , at each maternal age , who will be sent for amniocentesis . On the basis of the first French prospect i ve study of human chorionic gonadotropin ( hCG ) measurement in maternal serum , this paper shows that the screening protocol currently used in France , where hCG cut-off values are defined in order to offer amniocentesis to women of all ages with a 1 per cent fetal risk of Down 's syndrome , would detect 64.06 per cent of all cases of trisomy 21 at birth and would be highly profitable for the French social security system . On the basis of a representative sample of 100,000 pregnant women , the total costs of screening would reach $ 8,302,000 but would generate net potential savings of $ 32,186,000 in terms of life-long costs of care for trisomic 21 children which would be ' avoided ' by termination of pregnancy following a positive diagnosis of Down 's syndrome . Economic assessment shows that cost-benefit analysis would justify lower hCG cut-off values and a higher detection rate of fetal Down 's syndrome ( 74.45 per cent ) than the current French protocol . This paper concludes that it is ethical and value-laden issues , such as the consequences for women and couples of false positives and false negatives of screening , rather than economic and financial arguments that may set limits to the utilization of screening for Down 's syndrome using maternal serum markers like hCG During a prospect i ve study of the natural history of AIDS , 1001 homosexual or bisexual men were offered the opportunity to learn their HIV antibody status . Six hundred and seventy ( 67 % ) of the population who elected to do so were similar to the 331 ( 33 % ) people who declined in a number of baseline characteristics . All were counselled to practice safe sex . To determine whether disclosure of HIV serologic status affects subsequent sexual behavior , we examined changes at four time-points in three sexual activities during the previous 6 months : the number of male partners with whom the participant had ( 1 ) sexual intercourse , ( 2 ) unprotected anal receptive intercourse , and ( 3 ) unprotected anal insertive intercourse . All activities decreased strikingly over the 18-month study period . Following disclosure , the mean number of partners dropped to 47 % of the baseline number in people remaining unaware of their antibody status , to 45 % in people told that they were seropositive , and to 55 % in people told that they were seronegative . The mean number of partners for younger seropositives declined less than that for older seropositives . The mean number of partners with whom unprotected anal receptive intercourse was practice d declined to 57 % of baseline in unaware people , 42 % in aware seropositives , and 62 % in aware seronegatives . The mean number of partners with whom unprotected anal insertive intercourse was practice d declined to 52 % of baseline in unaware people , 42 % in aware seropositives and 59 % in aware seronegatives . Disclosure of a negative test result led to a significantly smaller decline in these sexual activities . ( ABSTRACT TRUNCATED AT 250 WORDS Abstract Objectives : To assess the experiences of obstetricians in Engl and and Wales of serum screening for Down 's syndrome . Design : Postal question naire survey . Subjects : Question naires were sent to all practising obstetricians in Engl and and Wales with non-academic20appointments who had not participated in an earlier ( r and omly sample d ) survey of obstetricians ' attitudes ( n=555 ) . Responses were received from 393 ( 71 % ) , of which 351 were analysed . The data represent about one third of obstetric consultants in Engl and and Wales . Main outcome measures : The extent of use of serum screening for Down 's syndrome , and the problems encountered . Results : Serum screening for Down 's syndrome was being offered on some basis by virtually all obstetricians in the survey . Nearly half the sample said that they did not have adequate re sources for counselling all the women to whom screening was offered . Many problems were reported , which in all cases were more common than equivalent problems encountered with serum screening for neural tube defects . Over 80 % ( 289 ) said that women not underst and ing the test was a problem . Conclusions : There is considerable confusion associated with serum screening for Down 's syndrome . The precedent of serum screening for neural tube defects does not seem to have lessened the problems experienced , rather the contrary . Many obstetricians report inadequate re sources for counselling , which is consistent with the high prevalence of problems associated with women not underst and ing the test . There is an urgent need to consider what counselling should consist of and who should undertake it and to ensure that necessary re sources are available We performed two studies using only written and video material s to educate people about cystic fibrosis ( CF ) and carrier screening . Participants were r and omized to receive written or video material s. All received a brief question naire . Subjects in group I ( n = 238 ) were ( 1 ) individuals in steady relationships and their partners , ( 2 ) > or = 18 years old , and ( 3 ) not pregnant . Those who accepted free screening and were not demonstrable carriers were sent a letter explaining their results and another question naire . Subjects in group II ( n = 108 ) were parents seeking well child care in a university clinic . The main outcome measures were ability to answer questions correctly about ( 1 ) health status of CF carriers and people with CF , ( 2 ) the possibility of false-negative results , and ( 3 ) for those who had screening , the implication s of their own results . Written and video material s were equally effective in conveying information . Prior to screening , subjects answered an average of 86 % of questions correctly . Subjects with less formal education answered fewer questions correctly ; 60 % of those with less than a high school education had adequate knowledge of the health consequences of having CF or being a carrier , compared with > or = 94 % of college graduates . Performance improved after screening . Where neither partner was a demonstrable carrier , 88 % knew their own and their partner 's test results , and 90 % indicated that their risk of having a child with CF was not zero . Written and video educational material s can be used without face-to-face counseling to inform most people about carrier screening and their test results . These material s may be less effective for those with lower educational background Objective To examine the prevalence and predictors of repeat HIV testing . Design , setting and participants Cross-sectional data from two r and om household- based and two bar-based sample s of gay/bisexual men in two medium-size cities ( Tucson , Arizona and Portl and , Oregon ) with substantial numbers of AIDS cases , in 1992 ( n = 2602 ) . Main outcome measureThe prevalence and predictors of repeat testing among men who reported being HIV-tested at least once but not being HIV-positive ( n = 1583 ) . Results In total , 51 % of the sample had been tested three or more times , and 15 % were tested more than once every 6 months . Men with higher risk were more likely to be repeatedly tested , although oral but not anal risk was a significant predictor of repeat testing in regression analyses . Men who did not know the HIV status of their primary partner were less likely to be repeatedly tested . Men who perceived that social norms favored secondary prevention , specifically adherence to medical recommendations for the treatment of HIV infection , and who communicated more often about testing were more likely to be repeatedly tested . Conclusions Policy and clinical recommendations for repeat testing must be based on consideration of the complexity and multi-faceted nature of repeat testing . For some individuals , repeat testing may play a legitimate role in HIV prevention by reinforcing safe behavior and providing confirmation of HIV-negative status . However , for others repeat testing may indicate a need for different or more intensive interventions to encourage safe sex This study aim ed to determine factors that influence fecal occult blood test performance in colorectal cancer screening . A r and om sample was selected of men and women ages 50 to 74 years of age who had been mailed a fecal occult blood testing kit in a screening program in fall 1986 . One year after initial test mailing , sample group members ( n = 504 ) were surveyed by telephone . Four months later , the survey sample received a second fecal occult blood test mailing . Multivariable analysis for subjects with vali date d past fecal occult blood test status ( n = 322 ) revealed the past testing was positively associated with physician encouragement of screening , age , the belief that cancer is curable , perceived test efficacy , and strong intention to do testing . It also was discovered that persons who felt that they had little control over their health were more likely to have done past testing . Preliminary analysis of prospect i ve adherence showed that the strongest statistically significant independent predictor was past test performance . Prospect i ve adherence among past nontesters ( n = 121 ) was associated with expressed commitment to do fecal occult blood testing and reported presence of colorectal cancer risk factors . Analysis of adherence among past testers ( n = 201 ) revealed that belief in colorectal cancer curability and age were significant predictors . The findings reported here indicate that factors influencing adherence among past nontesters differ from those for past testers . Overall , these results suggest that to increase participation in colorectal cancer screening , physicians and other health professionals should ( a ) deliver educational messages that increase awareness of risk factors for colorectal cancer and curability of the disease , and ( b ) elicit from potential screenees a commitment to engage in recommended preventive behaviors . It may also be well to consider " tailoring " messages for past nontesters and past testers , respectively , by emphasizing colorectal cancer risk factors and highlighting curability BACKGROUND The aim of this study was to describe the range of screening services offered by general practitioners ( GPs ) . METHODS A postal question naire survey was sent to a r and om sample of one in four GPs in general practice s within the geographical boundaries of North ( East ) Thames Region . The question naire was divided into five sections , the first covering practice details and the other four covering screening directed at different groups of patients . Each GP in the sample was sent the general section and two other sections . RESULTS The overall response rate was 67.7 per cent . There was inter-practitioner variability in screening practice in all four patient groups . A number of GPs did not undertake all screening tests required by the national GP contract or recommended by national or local policy , and some had introduced screening programmes of uncertain benefit . There was little evidence of systematic audit of screening programmes . Differences in screening provision were observed between GPs in Greater London and nonmetropolitan areas , but there was little difference between single-h and ed and group practice , or between fundholding and non-fundholding GPs , except in the provision of child health surveillance . CONCLUSION Primary care teams carry out screening for a wide range of conditions but the lack of uniformity of practice and of evaluation makes it unclear to what extent the population benefits from these activities . The importance of national and international screening policies is obvious , but there is a need to go beyond publication and dissemination of guidelines to develop implementation strategies which take account of the variations in the way GPs actually address screening in their practice In 1969 universal clinical screening for neonatal hip instability was formally adopted in the United Kingdom with the aim of detecting and treating children considered to be at high risk of congenital dislocation of the hip ( CDH ) . However , clinical screening is associated with both false positive and false negative diagnoses and has never been evaluated in a r and omised trial . The emergence of hip ultrasound provides renewed impetus to reconsider and formally evaluate screening for CDH . Ultrasound imaging of the newborn hip may be used as a screening test and to assess and manage infants with clinical ly detected hip instability . Universal primary ultrasound screening has been adopted in some European countries , but enthusiasm for this new technology has been tempered by the subsequent large ' increases in treatment and follow up . This paper review s the existing evidence to support the different approaches to screening and describes the research agenda of the MRC working party on congenital dislocation of the hip . A r and omised trial of screening is required to evaluate the policy options before ultrasound screening becomes widely adopted within the United Kingdom . The feasibility and acceptability of a trial need to be explored and key issues relating to trial design addressed The objective of this study was to assess the effects of two brief training interventions to improve obstetricians ' and midwives ' explanations to patients of a routine prenatal screening test . Health professionals were r and omly allocated to one of two intervention groups or a control group . Information-giving about the test and communication skills were assessed at baseline , post-training and 3-month follow-up from audiotaped consultations . Both intervention groups received a 1-h training session involving small group discussion s focused around a video . In addition , one group received individual feedback on their baseline and post-training consultations . Twenty-six midwives and nine obstetricians completed the study according to the protocol . Changes between baseline and post-training , and between baseline and follow-up , were computed . Information-giving and communication skills improved significantly in subjects receiving training and feedback on their performance , with the greatest improvements occurring before feedback was given . Those receiving training without feedback significantly improved their communication skills and showed some improvement in information-giving . These results show that modest improvements in communication can be made with relatively brief training . Greater and more sustained improvements may be found if all staff were trained , and trained on a regular basis Objective To find out how presenting information about the benefits of screening for cancer in different ways affects an individual 's decision to accept or reject screening . Methods A telephone survey of the Wellington region , New Zeal and was carried out . Results A response rate of 75.6 % was obtained . Respondents were most likely to accept screening when the benefits of screening were presented as a relative risk reduction . They were most likely to reject screening when the benefits were presented as numbers needed to screen to save one life . Conclusions An individual 's decision about screening for cancer is affected by the way the benefits are framed . Health professionals must choose between framing the benefits of screening in the most positive light , to enhance participation rates , and presenting information in such a way as to reduce framing effects — for example , by expressing the benefits in a variety of forms . Clearly there may be a tension between these approaches ; the former is arguably manipulation , and the latter may enhance informed choice , but may also reduce participation rates in screening programmes In this article we will review how a reader should evaluate a screening study . A clinical problem involving screening mammography is presented . We then outline criteria to determine whether screening is appropriate for a given condition . A search for relevant articles is described followed by an outline of the steps used to appraise a screening study critically . An applicable study is examined in detail for such things as the quality of r and omisation and outcomes measured . The results of this study are then applied to a patient considered for screening |
12,834 | 12,855,930 | DATA SYNTHESIS There is some evidence that potentially modifiable risk factors including poor endurance , lack of preseason training , and some psychosocial factors are important risk factors for injury in child and adolescent sport .
Sport participation and injury rates in child and adolescent sport are high . | OBJECTIVE The objective of this systematic review of the literature is to identify risk factors and potential prevention strategies that may modify risk factors for injury in child and adolescent sport . | OBJECTIVE To prospect ively document the incidence of game injury rates in youth ice hockey tournaments to compare with season-long game injury rates and to analyze the injuries occurring at tournaments by mechanism , type , body location , severity , player position , and period of play . DESIGN A prospect i ve injury report form completed for injured players by the tournament athletic trainer . SETTING Four boys ' tournaments and one girls ' tournament during the 1993 - 94 season . PARTICIPANTS 807 boys and girls , ages 9 - 19 . MEASUREMENTS /MAIN RESULTS 60 injuries occurred in boys and 4 occurred in girls . There were 26 boys with significant injuries and no girls with significant injuries . The significant game injury rates per 1000 player hours were 50.9 for boys combined , 57.9 for boys ' Peewee A , 42.7 for boys ' Bantam A , 64.8 for boys ' varsity high school , 44.8 for boys ' Junior Gold , and 0 for girls ' Peewee A and B. Cerebral concussion comprised 15 % of boys ' injuries . CONCLUSIONS The significant injury rate for boys ' tournament game play was 4 - 6 times higher than the season game injury rates in two previous season-long studies . In boys ' games , 65 % of " all " injuries and 77 % of " significant " injuries were related to collisions . The girls ' rules of play do not allow body checking , and there were no significant injuries in girls ' games . The boys had high rates of cerebral concussion injury at all age levels . Minimizing the frequency and intensity of collisions in the boys ' game may decrease the injury rates , especially in the tournament setting Eighty-six male high school ice hockey players partic ipated in this prospect i ve study to determine both the incidence of injury in high school ice hockey and the influence of physical , situational , and psychosocial fac tors . Physical factors included height , weight , vision , previous injuries , musculoskeletal abnormalities , and injuries present at the time of screening evaluations . Situational factors examined were level of participa tion , playing time , player position , and games versus practice s. Psychosocial factors such as confidence , stress , social support , positive states of mind , and mood states were also examined to determine their influences on injury . Twenty-seven injuries occurred during the 1994 to 1995 season . As hypothesized , the overall incidence of injury in high school hockey games ( 34.4 per 1000 player-game hours ) was less than the incidence of injury in Junior A hockey ( 96.1 per 1000 player-game hours ) and was more than previously re ported for Bantam youth hockey ( 10.9 per 1000 player- game hours ) . Injuries occurred more often in games than in practice s , usually as a result of collisions . Phys ical factors such as player position and previous inju ries did not significantly predict injuries , but players in the high playing time group were more likely to be injured . Psychosocial factors of low vigor and high fatigue as measured by the Incredibly Short Profile of Mood States ( ISPOMS ) significantly predicted high school ice hockey injuries Young female players in European h and ball have a very high injury incidence , up to 50 injuries per 1000 hours of game . More than half of these injuries happen without any external cause . The aim of the study was to investigate the effect of an intervention programme design ed to reduce the number of injuries in young female players in European h and ball , with special emphasis on injuries in the lower extremities . The programme was created using elite athlete training programmes and those design ed for rehabilitation of injured athletes with functional instability of their ankles and rupture of the anterior cruciate ligament . It included the use of an ankle disk for 10 - 15 min at all practice sessions , for one 10-month season ( August 1995-May 1996 ) . Twenty-two teams participated in the study , and were r and omly assigned to the intervention or control group . Eleven teams with 111 players were r and omised to the intervention group and 11 teams with 126 players to the control group . Data were analysed using a t-test for continuous variables , chi2- analysis and Fisher 's exact test for dichotomous variables and multivariate methods to determine odds-ratios . The results indicated that using the intervention programme decreased the numbers of both traumatic and overuse injuries significantly . The differences in injuries between the groups were 80 % during games and 71 % during practice . In addition , the players in the control group had a 5.9 times higher risk of acquiring an injury than the players in the intervention group OBJECTIVE To establish the previous rugby experience , the knowledge and the use of injury prevention techniques by South African schoolboy rugby players . DESIGN Before the first full-contact match of the 1991 rugby season , 2,330 players completed a detailed question naire . SETTING High schools in the Cape Province . Three thous and three hundred and thirty players from 25 schools selected because of a record of excellence in and commitment to schoolboy rugby . MAIN OUTCOME MEASURES Personal data including age , height , mass and rugby experience ; history and nature of previous rugby injuries ; knowledge of techniques known to prevent rugby injuries ; parental and personal reasons for playing rugby . RESULTS The incidence and distribution of the different types of injuries previously sustained by the players were the same as those identified prospect ively in the same population . A-team players were significantly heavier and taller than players in lower teams in most playing positions in most age groups . Although A-team players were more likely to participate in pre-season endurance or strength training , fewer than 40 % of players overall trained adequately in the pre-season . Less than 30 minutes was allocated to the practice of tackling and falling techniques prior to the first full-contact match . Knowledge of different high-risk situations during play was generally sketchy , and only 24 % of players wore gumguards all the time . More fathers ( 84 % ) than mothers ( 63 % ) encouraged their sons to play rugby . CONCLUSIONS The results indicate that the incidence and nature of the injuries reported retrospectively were similar to those reported in prospect i ve studies at the same schools . The players ' knowledge of techniques known to prevent rugby injuries was inadequate and too little attention was paid at the start of the rugby season to training and coaching techniques to reduce injury risk . Coaching errors may therefore have predisposed players to injury A prospect i ve study of injuries encountered during participation in a summer soccer camp for youths aged 6 through 17 years revealed an injury incidence of 10.6 per 1000 hours for girls ( 107 injuries in 458 girls ) and 7.3 per 1000 hours for boys ( 109 injuries in 681 boys ) . For both sexes , the incidence of injury increased at age 14 years . One certified athletic trainer ( W.D.C. ) assessed and documented all injuries during the course of the study . Seventy percent of injuries involved the lower extremities . Contusions represented 35.2 % , strains 27.8 % , sprains 19.4 % , and fractures and dislocations 2 % of all reported injuries . The ankle was the most frequent site of injury in both sexes . Quadriceps strain was a common injury in boys . The boys with the highest incidence of injury were tall ( greater than 165 cm ) and had a weak grip ( less than 25 kg ) , suggesting that skeletally mature but muscularly weak boys may be more susceptible to injury while playing soccer with peers of the same chronological age OBJECTIVE To determine the rate , type , and severity of injuries to child hockey players as well as assessing coaches ' , parents ' , and players ' attitudes and knowledge of hockey . DESIGN A prospect i ve observation of a population 's injuries using injury-reporting forms and surveys . SETTING A community-organized hockey program in Minnesota . PARTICIPANTS One hundred fifty boys , aged 9 through 15 years , who played ice hockey during the 1990 - 1991 winter season . MEASUREMENTS AND MAIN RESULTS Injuries were reported by multiple observers , including coaches , managers , and trained independent observers at the time an injury occurred ; coaches , parents , and players were surveyed regarding hockey injuries , knowledge , and attitudes . One in three players experienced an injury during the season . The most common injuries were contusions . Six of 100 players experienced injuries severe enough to require cessation of physical activities for 8 to 25 days or longer . Weight differences of 53 kg and height differences of 55 cm were reported between Bantam-aged players ( 13 through 15 years ) , and body contact , including legal checks , accounted for 86 % of injuries during games . Illegal checks and violations were associated with 66 % of injuries during games , yet only four penalties ( 14 % ) were assessed . In addition , one in three games in which an injury result ed was described as hostile and 15 % of the injuries were considered intentional . CONCLUSIONS Eliminating violence and body checking for prepubertal boys while emphasizing rule enforcement and good sportsmanship are recommended Physical training-related injuries are common among army recruits and other vigorously active population s , but little is known about their causation . To identify intrinsic risk factors , we prospect ively measured 391 army trainees . For 8 weeks of basic training , 124 men and 186 women ( 79.3 % ) were studied . They answered question naires on past activities and sports participa tion , and were measured for height , weight , and body fat percentage ; 71 % of the subjects took an initial army physical training test . Women had a significantly higher incidence of time-loss injuries than men , 44.6 % com pared with 29.0 % . During training , more time-loss in juries occurred among the 50 % of the men who were slower on the mile run , 29.0 % versus 0.0 % . Slower women were likewise at greater risk than faster ones , 38.2 % versus 18.5 % . Men with histories of inactivity and with higher body mass index were at greater injury risk than other men , as were the shortest women . We conclude that female gender and low aerobic fitness measured by run times are risk factors for training injuries in army trainees , and that other factors such as prior activity levels and stature may affect men and women differently We performed a prospect i ve study to evaluate injury patterns in a large population of high school wrestlers during one season . Preseason screening was performed on 458 male wrestlers from 14 different high schools . Certified athletic trainers su bmi tted detailed weekly team and individual injury reports . There were 219 injuries in 418 wrestlers followed throughout the season for an overall injury incidence of 52 injuries per 100 wrestlers per season and an injury rate of 6.0 injuries per 1000 exposures . The most commonly injured areas were the shoulder ( 24 % ) and knee ( 17 % ) . Injured wrestlers were an average of 5 months older and had a 32 % higher experience level than noninjured wrestlers . Wrestlers with ligamentous laxity suffered fewer shoulder injuries than the other wrestlers . The majority of injuries occurred in practice ( 63 % ) , although the injury rate was higher in match competitions . Sixty-eight percent of practice injuries occurred during hard wrestling , 23 % during drills , and 9 % during conditioning . The most common wrestling situation result ing in injury was the takedown position ( 68 % ) . Our results show that the older and more experienced wrestler may be at greater risk of injury . Hard wrestling during practice and the takedown position result ed in the highest occurrence of injury Proprioceptive training has been shown to reduce the incidence of ankle sprains in different sports . It can also improve rehabilitation after anterior cruciate ligament ( ACL ) injuries whether treated operatively or nonoperatively . Since ACL injuries lead to long absence from sports and are one of the main causes of permanent sports disability , it is essential to try to prevent them . In a prospect i ve controlled study of 600 soccer players in 40 semiprofessional or amateur teams , we studied the possible preventive effect of a gradually increasing proprioceptive training on four different types of wobble-boards during three soccer seasons . Three hundred players were instructed to train 20 min per day with 5 different phases of increasing difficulty . The first phase consisted of balance training without any balance board ; phase 2 of training on a rectangular balance board ; phase 3 of training on a round board ; phase 4 of training on a combined round and rectangular board ; phase 5 of training on a so-called BABS board . A control group of 300 players from other , comparable teams trained “ normally ” and received no special balance training . Both groups were observed for three whole soccer seasons , and possible ACL lesions were diagnosed by clinical examination , KT-1000 measurements , magnetic resonance imaging or computed tomography , and arthroscopy . We found an incidence of 1.15 ACL injuries per team per year in the control group and 0.15 injuries per team per year in the proprioceptively trained group ( P<0.001 ) . Proprioceptive training can thus significantly reduce the incidence of ACL injuries in soccer players Background : Risk factors for soccer injuries and possibilities for prevention have been discussed by several authors , but only a few have investigated the effectiveness of preventive interventions . Purpose : The aim of the present study was to evaluate the effects of a prevention program on the incidence of soccer injuries in male youth amateur players . Study Design : Prospect i ve controlled intervention study . Methods : Seven soccer teams took part in a prevention program that focused on education and supervision of coaches and players , while seven other teams were instructed to train and play soccer as usual . Over 1 year all injuries were documented weekly by physicians . Complete weekly injury reports were available for 194 players . Results : The incidence of injury per 1000 hours of training and playing soccer was 6.7 in the intervention group and 8.5 in the control group , which equates to 21 % fewer injuries in the intervention group . The greatest effects were observed for mild injuries , overuse injuries , and injuries incurred during training . The prevention program had greater effects in low-skill than in high-skill teams . Conclusions : The incidence of soccer injuries can be reduced by preventive interventions , especially in low skill level youth teams . Coaches and players need better education regarding injury prevention strategies and should include such interventions as part of their regular training Recent publications have reported differences in the incidence , rate , risk , and type of sports injury among men and women . We undertook a prospect i ve study to determine the incidence of injury among high school basketball players and to examine the differences in injury type , incidence , rate , and risk between male and female athletes . During a single basketball season , an injury survey of girls ' varsity teams at 100 class 4A and 5A high schools in Texas was conducted . These data were previously reported . We surveyed the same 100 high schools during a subsequent season to gather injury data from the boys ' varsity teams . The athletic trainer collected data on each reportable injury and reported the data weekly to the University Interscholastic League . A reportable injury was defined as one that occurred during a practice or a game , result ed in missed practice or game time , required physician consultation , or involved the head or the face . The boys ' and girls ' data were compared and statistically analyzed . The rate of injury was 0.56 among the boys and 0.49 among the girls . The risk of injury per hour of exposure was not significantly different between the two groups . In both groups , the most common injuries were sprains , and the most commonly injured area was the ankle , followed by the knee . Female athletes had a significantly higher rate of knee injuries including a 3.79 times greater risk of anterior cruciate ligament injuries . For both sexes , the risk of injury during a game was significantly higher than during practice Among school-aged children , unintentional injuries are the leading cause of morbidity and mortality . We began this prospect i ve study in a sample of nine schools within the Boulder Valley School District ( Colorado ) during the 1988 - 1989 school year in an effort to explore the etiology of school-related injuries and to provide information relevant to their prevention . During the study period , 509 injuries were reported among a population of 5,518 students , yielding an incidence of 9.22 per 100 students . Boys were nearly one and one-half times more likely to have sustained a school-related injury than girls ( risk ratio ( RR ) = 1.41 ; 95 % confidence intervals [ CIs ] 1.18 , 1.68 ) . We found a significant difference among injury rates by school level ( P less than .001 ) . Middle/junior high students had the highest rate , followed closely by elementary students and distantly by high school students . Sports activities accounted for the largest percentage of school injuries ( 53 % ) , and the percentage of sports-related injuries increased with increasing grade level . Analysis of injury rates by school location revealed that high school students were most frequently injured in the gym ( 1.52 per 100 ) , middle/junior high students on the athletic field ( 4.26 per 100 ) , and elementary students on the playground ( 6.12 per 100 ) . Using injury location as the focal point , we examined relationships among the variables sport/activity , body site , and nature of injury . We found that a large percentage of injuries sustained on the athletic field or in the gym were similar and affected similar body sites , whereas playground injuries differed in their nature and in body site affected . ( ABSTRACT TRUNCATED AT 250 WORDS In a prospect i ve study of 302 adolescent players in three ball games ( soccer , h and ball and basketball ) , 119 incurred injuries . The injury incidence ( number of injuries per 1000 playing hours ) was 5.6 in soccer , 4.1 in h and ball and 3.0 in basketball . Ankle sprains accounted for 25 per cent of the injuries , finger sprains 32 per cent , strains in the thigh and leg 10 per cent , and tendinitis/apophysitis 12 per cent . The most serious injuries were four fractures , one anterior cruciate ligament rupture , and two meniscus lesions . The most serious injuries , with the longest rehabilitation period , occurred in soccer . In soccer , many injuries occurred during tackling and contact with an opposing player , while the injuries in h and ball and basketball were often caused by ball contact and running OBJECTIVE To evaluate the relationship between changes in physical fitness and risk of mortality in men . DESIGN Prospect i ve study , with two clinical examinations ( mean interval between examinations , 4.9 years ) to assess change or lack of change in physical fitness as associated with risk of mortality during follow-up after the subsequent examination ( mean follow-up from subsequent examination , 5.1 years ) . SETTING Preventive medicine clinic . STUDY PARTICIPANTS Participants were 9777 men given two preventive medical examinations , each of which included assessment of physical fitness by maximal exercise tests and evaluation of health status . MAIN OUTCOME MEASURES All cause ( n = 223 ) and cardiovascular disease ( n = 87 ) mortality . RESULTS The highest age-adjusted all-cause death rate was observed in men who were unfit at both examinations ( 122.0/10,000 man-years ) ; the lowest death rate was in men who were physically fit at both examinations ( 39.6/10,000 man-years ) . Men who improved from unfit to fit between the first and subsequent examinations had an age-adjusted death rate of 67.7/10,000 man-years . This is a reduction in mortality risk of 44 % ( 95 % confidence interval , 25 % to 59 % ) relative to men who remained unfit at both examinations . Improvement in fitness was associated with lower death rates after adjusting for age , health status , and other risk factors of premature mortality . For each minute increase in maximal treadmill time between examinations , there was a corresponding 7.9 % ( P = .001 ) decrease in risk of mortality . Similar results were seen when the group was stratified by health status , and for cardiovascular disease mortality . CONCLUSIONS Men who maintained or improved adequate physical fitness were less likely to die from all causes and from cardiovascular disease during follow-up than persistently unfit men . Physicians should encourage unfit men to improve their fitness by starting a physical activity program OBJECTIVE This study was conducted to identify the circumstances , timing , frequency , and types of injuries for a Junior A hockey team in an attempt to develop injury prevention strategies . DESIGN This study was a prospect i ve review of injuries sustained by a hockey team during one season . SETTING Players were evaluated in a private practice clinical setting and during practice s and games . PARTICIPANTS Twenty-two hockey players ( 16 - 20 years old ) were evaluated . An injury was defined as any event requiring the attention of a physician or trainer . The players sustained 83 injuries throughout the course of the season . Seventy-four were considered independent events . MAIN OUTCOME MEASURES The effects of the following variables on injury rates were analyzed : position , game situation versus practice , and timing of injury during the game . RESULTS Players were 20 times more likely to injure themselves during a game than practice . Although forwards sustained the highest total percentage of injuries , defensemen had the highest incidence of injury in games . More injuries occurred in the later periods and in the later minutes of each period . Injury incidence decreased for the second half of the season compared with the first half . CONCLUSION Our data suggest goal tenders are at the lowest risk of sustaining an injury , but forwards appear to be at a higher risk in practice situations and defensemen in games . Game situations place players at a much greater risk of injury than practice sessions , particularly in the later portions of each period and toward the end of the game . Given the propensity for injury in the early season and later in the game , endurance training before and during the season may be important in injury prevention PURPOSE To report the prevalence of recent adolescent recreational and sporting activities and associated injury . METHODS Data were collected during three school terms in 1997 using a vali date d question naire administered once only to 3538 girls and boys aged 11 - 12 years and 15 - 16 years . These students comprised 97.5 % of the students in these age ranges in r and omly selected state and private schools in the Adelaide metropolitan area ( South Australia ) . Participants identified up to three recreational and /or sporting activities in which they had participated in the previous week . Data were collected on the nature and extent of participation , and on associated injuries . Participation and injury reports were summarized descriptively in gender strata in the two adolescent age groups and stratum specific odds ratios were used to explore injury risk . RESULTS Subjects reported participating in 8997 sporting and /or recreational activities in the preceding week ( an average of 2.5 participations per student ) . Over 140 sports and recreational pursuits were represented , incorporating organized and nonorganized activities undertaken in teams , social groups , or alone . Approximately 25 % of adolescents reported at least one recreational injury . Injuries were mostly minor , reflecting soft tissue trauma and skin abrasions . Organized group sport incurred the highest risk of injury . There were marked gender and year level differences in injury risk in a number of common activities . CONCLUSIONS These findings support the need for ongoing education regarding injury prevention and management One hundred and seventy-two r and omly selected high-school football players underwent pre-season isokinetic muscle-testing to determine if there was any relationship between an imbalance in thigh-muscle function and the occurrence of knee injuries . Strength , power , power-endurance , and time to maximum tension were measured for the quadriceps and hamstring muscle groups for both lower extremities of each athlete . The result ing values were utilized to see if a difference of 10 per cent or more between the right and left extremities or between the mean and actual hamstring-to-quadriceps ratio of the individual extremity would result in more knee injuries . No such relationship was found OBJECTIVE To determine the risk of injury in youth football games . SUBJECTS AND METHODS Nine hundred fifteen players aged 9 to 13 years on 42 teams participated , including 10 teams in each grade from grade s 4 through 6 and 6 teams each in grade s 7 and 8 . The study was conducted in the fall of 1997 . Injury incidence , prevalence , and severity were calculated for each grade level and player position . Additional analyses examined the number of injuries according to body weight . RESULTS A total of 55 injuries occurred in games during the entire season ( overall prevalence , 5.97 % ) . Most injuries were mild , and the most common type was contusion , which occurred in 33 players ( 60 % ) . Four injuries ( 7 % ) were severe enough to prevent players from participating for the rest of the season . All 4 severe injuries were fractures involving the ankle physis . The risk of injury increased as players matured in age and grade level . Injury risk for an eighth- grade player was 4 times greater than the risk of injury to a fourth- grade player . A trend was identified for heavier players to be at increased risk , but no significant correlation was evident between body weight and injury . CONCLUSION Our prospect i ve observational analysis showed that most youth football injuries are mild . Older and heavier players appear to be at higher risk There are 300,000 to 1,215,000 high-school football injuries each year in the United States . These injuries have an important effect on player participation and health care costs . This study investigates what portion of injuries occur during the third quarter of a game , and if completing a warm-up and stretching routine after halftime reduces the incidence of third-quarter injuries . Intervention-group teams participated in a prescribed three-minute warm-up and stretching routine following the halftime break . The control group received no warm-up and stretching intervention . Fifty-five games with 108 total injuries were examined . Overall , ligament sprains and muscle strains were the most common type of injury ( 38 % ) . In the nonintervention group , injuries occurred most often in the third quarter . Intervention teams sustained significantly fewer third-quarter sprains and strains per game ( p less than 0.05 ) , although no significant difference in total third-quarter injuries was noted . These findings suggest an association between post-halftime warm-up and stretching and reduced third-quarter sprain and strain injuries . We suggest a larger-scale , r and omized confirmatory study PURPOSE Previous studies among young pitchers have focused on the frequency and description of elbow injuries . The purpose of this study was to evaluate the frequency of elbow and shoulder complaints in young pitchers and to identify the associations between pitch types , pitch volume , and other risk factors for these conditions . METHODS A prospect i ve cohort study of 298 youth pitchers was conducted over two seasons . Each participant was contacted via telephone after each game pitched to identify arm complaints . Generalized estimating equations were used to assess associations between arm complaints and independent variables . RESULTS The frequency of elbow pain was 26 % ; that of shoulder pain , 32 % . Risk factors for elbow pain were increased age , increased weight , decreased height , lifting weights during the season , playing baseball outside the league , decreased self-satisfaction , arm fatigue during the game pitched , and throwing fewer than 300 or more than 600 pitches during the season . Risk factors for shoulder pain included decreased satisfaction , arm fatigue during the game pitched , throwing more than 75 pitches in a game , and throwing fewer than 300 pitches during the season . CONCLUSION Arm complaints are common , with nearly half of the subjects reporting pain . The factors associated with elbow and shoulder pain were different , suggesting differing etiologies . Developmental factors may be important in both . To lower the risk of pain at both locations , young pitchers probably should not throw more than 75 pitches in a game . Other recommendations are to remove pitchers from a game if they demonstrate arm fatigue and limit pitching in nonleague games Little is known about the relative injury risk of obese adolescent football players . Two high school varsity teams were followed prospect ively for injuries after measurement of height , weight , and triceps and subscapular skinfolds during the preseason . Certified athletic trainers who were present at all practice s recorded all injuries that required a player to miss at least one practice or game . In all , 98 players were enrolled in the study . Twenty-eight injuries were documented in 24 different players . There were 27 ( 28 % ) players with the sum of skinfolds > or = 95th percentile for age ; eight of them had nine injuries . The overall prevalence of injuries per player per season was 0.28 for players < or = 95th percentile and 0.33 for players above this percentile ( not significant ) . High body mass ( body weight > 90 kg ) was associated with a 2.5 times higher relative risk of injury . While this study did not find evidence for an overall higher injury rate in overly fat high school football players , an alarmingly high incidence of obesity was found in this athletic population The 1996 Alberta Sport and Recreation Injury Survey is a retrospective study describing the annual incidence of injuries in the province of Alberta result ing from sport and recreational involvement . Data was collected by means of a telephone survey using r and om digit dialing techniques to obtain a representative sample of Albertans in the winter of 1995 - 96 . The sample produced a total of 3,790 respondents from 1,478 households evenly split between genders , with an age range of 6 to 93 years . The survey asked information regarding medically attended , non-fatal injuries result ing from sport and recreational activities . Findings reveal an annual incidence of sport or recreational injuries of 11 % . Among those reporting a sport or recreational injury , the most common types of injuries were a sprained/torn ligament ( 31 % ) , strained/pulled muscle ( 19 % ) , and fracture ( 13 % ) . The most common bodily locations of injuries were the knees ( 21 % ) and the ankle ( 14 % ) This prospect i ve study examined injury incidence , injury type , causative factors , and effect on playing status for injuries occurring among soccer players in a invitational tournament . Injury incidence was 23.8/10,000 player hours , and 62.5 % were mild , with contusions , sprains , and strains predominating . Player to player contact , and player to ground contact accounted for 67 % of the injuries . Females had a higher incidence of injuries . These results support other studies that show soccer is a relatively safe sporting activity for youth . Implication s for continued safety may include adjustments in playing conditions for females , proper preparation of playing surfaces , education of coaches about safe coaching practice s , and consistent refereeing OBJECTIVE To ascertain the incidence , severity , risk factors , and outcomes of injuries in children and adolescents playing Australian Rules football . DESIGN SETTING AND SUBJECTS A prospect i ve cohort study of football injuries in children and adolescents playing community football . We studied a stratified r and om sample of 54 teams and clinics ( 18 under-15 teams , 18 under-10 teams and 18 Vickick clinics for children under 10 years ) from the Melbourne metropolitan area . Football exposure , injuries and associated risk factors were recorded for 1253 players during the 1992 football season . RESULTS Vickick , a modified form of the game , had the lowest rates of injury for all levels of injury severity , with an overall rate of 3.49 injuries per 1000 player-hours . The rate in the under-10 age group was 2.4 times higher ( 95 % confidence interval [ CI ] , 1.5 - 3.8 ) than that in Vickick , and the under-15 rate was 1.2 times ( 95 % CI , 0.9 - 1.6 ) that of the under-10s . The under-15 age group had significantly more injuries that led to use of health services than the under-10 and Vickick groups , with rates of 3.93 ( 95 % CI , 2.9 - 4.9 ) , 0.64 ( 95 % CI , 0.2 - 1.4 ) , and 0.33 ( 95 % CI , 0.1 - 0.8 ) injuries per 1000 players-hours respectively . Injuries were largely to soft tissues ( sprains 26 % , haematomas 25 % ) and to the lower limb ( 43 % ) . Very few serious injuries occurred ( 19 fractures and three injuries with loss of consciousness ) ; nearly all of these were in the under-15s . Rule modifications in under-10 teams and clinics were associated with an injury rate of 5.8 injuries per 1000 player-hours ( 95 % CI , 4.4 - 7.3 ) compared with 7.5 injuries per 1000 player-hours ( 95 % CI , 5.2 - 9.8 ) when no modification was used . Alterations to the ruck contest , decreased contact , field size and player numbers were significantly associated with lower injury rates , while body size was not . Of the 30 % of injuries result ing in a health service consultation , the most common health provider was a medical practitioner . Very few required expensive investigation or treatment . CONCLUSION Injury rates were low in children under age 10 , but higher in adolescents . Most injuries were minor , and did not result in a health professional consultation . Rule modifications were associated with substantially lower injury rates at the under-10 level , and should be promoted as a safe way to learn football skills Soccer has rapidly gained in interest in the United States . A paucity of available data on soccer injuries led us to formulate this study to quantitate and categorize injuries acquired during a program of youth soccer ( under age 19 ) . A prospect i ve study of 1,272 players showed an injury rate of 2.6 injuries per 100 participants . The injury rate for girls was twice as great as for boys . The under 10-age group was seldom injured ( less than 1 injury per 100 participants ) , but the overall injury rate in the players of secondary school age was 7.7 injuries per 100 partic ipants . Most injuries were not serious . Soccer appears to be a safe activity for adolescents and children |
12,835 | 18,850,025 | The exploratory comparison between classes of drugs revealed no significant difference in dyspeptic symptoms reduction between CNS and prokinetic drugs ; however CNS drugs were associated with a larger reduction in symptoms as compared with antisecretory drugs .
CONCLUSIONS The results show that both CNS and classic drugs are associated with a significant pain reduction in functional dyspepsia | BACKGROUND Recent evidence has suggested that pain in functional dyspepsia ( FD ) is associated with nervous system dysfunction ; indicating that therapies aim ed at nervous system modulation might be associated with pain relief in FD .
OBJECTIVE To conduct a systematic review and meta- analysis to quantify the efficacy of drugs targeting the central nervous system ( antidepressants and antianxiety agents - referred as " CNS drugs " ) and drugs targeting gastric modulation ( antisecretory and prokinetic - referred as " classic drugs " ) for the treatment of pain in FD and , in an exploratory way , compare these 2 modalities of treatment . | BACKGROUND / AIMS Although antidepressants have been used for decades in treating patients with functional abdominal syndromes , how they influence gastrointestinal motility remains unclear . We aim ed to assess the role of depression in functional dyspepsia , and the effect of antidepressants on the functional dyspepsia patients ' symptoms and gastric myoelectrical activity . METHODOLOGY We conducted an open clinical trial with 40 functional dyspepsia patients . Zung self-rating depression scale was used in evaluating the patients ' depression . Cutaneous electrogastrography and evaluation of upper gastrointestinal symptoms were performed before and after administration of a one-month course of fluoxetine . RESULTS In the baseline study , the depressed functional dyspepsia patients had higher symptom scores than non-depressed patients ( P < 0.05 ) . The depressed functional dyspepsia patients had higher percentages of tachygastria than healthy controls ( P < 0.05 ) , but the electrogastrography parameters of depressed and non-depressed functional dyspepsia patients were not different . After one-month fluoxetine treatment , the symptom scores improved significantly in the depressed functional dyspepsia patients ( P < 0.05 ) , but not in the non-depressed patients . Electrogastrography did not improve in either group . CONCLUSIONS Depressive functional dyspepsia patients had higher symptom scores and responded well to fluoxetine treatment . However , electrogastrography did not improve after the treatment . These findings suggest that depression is significant in the presentation of functional dyspepsia symptoms , but not correlated with gastric myoelectrical activity BACKGROUND The treatment of patients with functional dyspepsia remains unsatisfactory . We assessed the efficacy of itopride , a dopamine D2 antagonist with anti-acetylcholinesterase [ corrected ] effects , in patients with functional dyspepsia . METHODS Patients with functional dyspepsia were r and omly assigned to receive either itopride ( 50 , 100 , or 200 mg three times daily ) or placebo . After eight weeks of treatment , three primary efficacy end points were analyzed : the change from baseline in the severity of symptoms of functional dyspepsia ( as assessed by the Leeds Dyspepsia Question naire ) , patients ' global assessment of efficacy ( the proportion of patients without symptoms or with marked improvement ) , and the severity of pain or fullness as rated on a five- grade scale . RESULTS We r and omly assigned 554 patients ; 523 had outcome data and could be included in the analyses . After eight weeks , 41 percent of the patients receiving placebo were symptom-free or had marked improvement , as compared with 57 percent , 59 percent , and 64 percent receiving itopride at a dose of 50 , 100 , or 200 mg three times daily , respectively ( P<0.05 for all comparisons between placebo and itopride ) . Although the symptom score improved significantly in all four groups , an overall analysis revealed that itopride was significantly superior to placebo , with the greatest symptom-score improvement in the 100- and 200-mg groups ( -6.24 and -6.27 , vs. -4.50 in the placebo group ; P=0.05 ) . Analysis of the combined end point of pain and fullness showed that itopride yielded a greater rate of response than placebo ( 73 percent vs. 63 percent , P=0.04 ) . CONCLUSIONS Itopride significantly improves symptoms in patients with functional dyspepsia . ( Clinical Trials.gov number , NCT00272103 . ) In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis . Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were r and omized to receive cisapride ( 10 mg ) or matching placebo three times daily for 4 weeks . Symptoms of epigastric pain , bloating , nausea , belching , early satiety and heartburn were grade d on a four-point scale based on patients ' feedback and diary card recording . A global response was also formulated by the investigators . One hundred and four patients entered the study and 76 completed the trial , comprising 36 patients with histological gastritis and 40 patients without gastritis . Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo ; however , the improvement was not statistically different between the two treatment groups . Cisapride produced a good or better global response in 58 % of subjects with histological gastritis and in 53 % of subjects without gastritis compared with 47 % and 52 % , respectively , of patients on placebo ; this difference was not statistically significant . Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia Background : The use of proton pump inhibitors for the treatment of functional dyspepsia is controversial and the role of Helicobacter pylori infection in functional dyspepsia is uncertain . Aim : To evaluate the efficacy of different doses of lansoprazole for the treatment of functional dyspepsia in Chinese patients . Method : Patients with a clinical diagnosis of functional dyspepsia according to the Rome II criteria and normal upper gastrointestinal endoscopy were recruited and r and omised to receive : ( 1 ) lansoprazole 30 mg,(2 ) lansoprazole 15 mg , or ( 3 ) placebo , all given daily for four weeks . Dyspepsia symptom scores and quality of life ( SF-36 score ) were evaluated before and four weeks after treatment . Results : A total of 453 patients were r and omised . There was no difference in the proportion of patients with complete symptom relief in the lansoprazole 30 mg ( 23 % ) and lansoprazole 15 mg ( 23 % ) groups compared with the placebo group ( 30 % ) . The proportion of H pylori positive patients with a complete response was similar with lansoprazole 30 mg ( 34 % ) and lansoprazole 15 mg ( 20 % ) versus placebo ( 22 % ) . All symptom subgroups ( ulcer-like , dysmotility-like , reflux-like , and unspecified dyspepsia ) had similar proportions of patients with complete symptom relief after treatment . Conclusion : Proton pump inhibitor treatment is not superior to placebo for the management of functional dyspepsia in Chinese patients Background and aims : Patients with functional dyspepsia who have hypersensitivity to gastric distension have more prevalent pain , suggesting the presence of hyperalgesia . It is unclear whether this reflects activation of pain specific afferent pathways or multimodal afferent pathways that also mediate non-painful sensations . In the former case , hyperalgesia should occur when intensity of non-painful sensations is still low . The aim of the study was to analyse whether the symptom profile during gastric dissentions in functional dyspepsia patients with hyperalgesia reflects sensitisation of pain specific or multimodal pathways . Methods : Forty eight consecutive dyspeptic patients ( 35 female ) underwent gastric sensitivity testing with a barostat balloon using a double r and om staircase protocol . At the end of every distending step , patients scored perception of upper abdominal sensations on a graphic 0–6 rating scale and completed visual analogue scales ( VAS 0–100 mm ) for pain , nausea , satiety , and fullness . The end point was a rating scale of 5 or more . Results : Hypersensitivity was present in 20 patients ( 40 % ) ; gastric compliance did not differ between normo- and hypersensitive patients . At maximal distension ( score 5 or more ) , hypersensitive patients had significantly lower distending pressures and intra-balloon volumes , but similar VAS scores for pain , nausea , satiety , and fullness compared with normosensitive patients . In both normosensitive and hypersensitive patients , elevation of pain VAS scores with increasing distending pressures paralleled the elevation in VAS scores for nausea , satiety , and fullness . Conclusions : Hypersensitive dyspeptic patients reach the same intensity of painful and non-painful sensations as normosensitive patients but at lower distending pressures . Hyperalgesia occurs in hypersensitive dyspeptic patients at distending pressures that also induce intense non-painful sensations . These findings argue against isolated upregulation of pain specific afferents in functional dyspepsia patients with visceral hypersensitivity Objectives Levosulpiride is the levo-enantiomer of sulpiride , a well-known antiemetic , antidyspeptic and antipsychotic drug . This study was undertaken to investigate the effects of levosulpiride on dyspeptic symptoms and gastric motor function in a group of patients with functional dyspepsia showing delayed gastric emptying . Method Forty two eligible patients were entered into a 3 week , double-blind r and omized comparison of 25 mg of levosulpiride or placebo t.i.d .. Symptom assessment and gastric scintigraphy following the intake of scrambled egg s and wich , were performed in each patient before and after treatment . Results The improvement of symptom score in levosulpiride group was higher than the placebo group ( p<0.05 ) . We assessed global efficacy , which was excellent in 1 ( 6 % ) , good 11 ( 65 % ) , fair 4 ( 24 % ) , nil 1 ( 6 % ) of those receiving levosulpiride , and fair 9(60 % ) , nil 5 ( 33 % ) , poor 1 ( 6 % ) of those receiving placebo . Levosulpiride tended to be more effective than placebo in relieving the dyspeptic symptoms especially in the subgroups of dysmotility-like ( p<0.05 ) and nonspecific ( p<0.05 ) as compared to other subgroups ( p=0.16 ) . The reduction of gastric emptying time after levosulpiride treatment was more marked than Placebo group ( p<0.05 ) . We found a significant correlation between changes of symptom score and gastric emptying time ( r=0.47 , p=0.01 . No serious adverse effects were reported after administration of either levosulpiride or placebo . Only two patients reported mild somnolence during levosulpiride administration . Conclusions Levosulpiride is effective and well tolerated in patients with functional dyspepsia accompanied by delayed gastric emptying . Its efficacy may be related to its action on the gastric motor function by improving the delayed gastric emptying AIM To compare ecabet sodium and cimetidine in relieving symptoms of functional dyspepsia . METHODS We performed a multi-center , prospect i ve , r and omized , double-blinded controlled trial to compare the clinical efficacy of ecabet sodium and cimetidine in patients with functional dyspepsia . Two-hundred and seventy-two patients with dyspeptic symptoms fulfilling the Rome-II criteria were enrolled from 7 centers . In the study group ( 115 patients ) , 1.5 g ecabet sodium was given twice a day . In the control group ( 121 patients ) , 400 mg cimetidine was given twice a day . Symptoms and parameters of quality of life were analyzed at baseline , 3 , 14 , and 28 d after initiating the treatment . RESULTS Two-hundred and thirty-six patients completed the clinical trial . After 4 wk of treatment , the rates of improvement in patients with dyspeptic symptoms were not different between two groups ( 77.4 % in the ecabet group and 79.3 % in the cimetidine group , respectively , P > 0.05 ) . Likewise , the rates of symptomatic improvement were not different at 3 d and 14 d. The parameters of quality of life did not change significantly during the study period in both groups . There was no clinical ly significant adverse event in both groups . CONCLUSION In patients with functional dyspepsia , ecabet sodium has similar clinical efficacy with cimetidine Background : The treatment of functional dyspepsia is controversial Altered visceral perception is common in functional dyspepsia ( FD ) . Dopaminergic pathways control gastrointestinal motility , but whether they modulate visceral sensitivity is unknown Nonulcer dyspepsia ( NUD ) is a common syndrome , but the optimal treatments have yet to be established . This study was performed to determine the most effectivetreatment for NUD . Subjects were recruited through the Department of General InternalMedicine at the Kyushu University Hospital because oftheir somatic symptoms . When no organic lesions werefound , the patients were directed to consult ourdepartment ( Psychosomatic Medicine ) ; 194 consecutive NUD patients were studied . All subjects were assessedpsychiatrically with the Structured Clinical Interviewfor DSM-III-R(SCID ) . Patients with serious NUD were hospitalized , and r and omly divided into control(N = 42 ) and experimental groups ( N = 86 ) . The controlswere treated with physical treatment alone . Theexperimental group received psychiatric treatment inaddition , based on the results of SCID . The experimentalgroup showed a significant improvement compared with thecontrols ( P < 0.0001 ) . The treatment for NUD takinginto consideration both the physical and psychiatric conditions is highly effective Aim : To compare the efficacy of simethicone with placebo and the prokinetic cisapride in patients with functional dyspepsia BACKGROUND & AIMS Hypersensitivity to proximal gastric distention as a result of abnormal central nervous system processing of visceral stimuli is a possible pathophysiologic mechanism in functional dyspepsia ( FD ) . Increasing evidence suggests involvement of both lateral and medial pain systems in normal visceral sensitivity and aberrant brain activation patterns in visceral hypersensitivity . We hypothesized that there is involvement of aberrant brain activation in FD with hypersensitivity to gastric distention . Our aim was to investigate regional cerebral blood flow during painful proximal gastric distention in hypersensitive FD . METHODS Brain (15)O-water positron emission tomography was performed in 13 FD patients with symptoms of gastric hypersensitivity during 3 conditions : no distention , sham distention , and isobaric distention to unpleasant or painful sensation . Pain , discomfort , nausea , and bloating during maximal distention were rated on visual analogue scales . Data were analyzed using statistical parametric mapping . RESULTS The threshold for painful distention was 6.6 + /- 3.8 mm Hg greater than the minimal distending pressure . At the corrected P level of less than .05 , subtraction analysis ( painful distention - no distention ) showed activations in bilateral gyrus pre central is , bilateral gyrus frontalis inferior , bilateral gyrus frontalis medialis , bilateral gyrus temporalis superior , bilateral cerebellar hemisphere , and left gyrus temporalis inferior . Sham distention minus no distention showed no activations . CONCLUSIONS Similar to healthy volunteers , proximal stomach distention in FD activates components of the lateral pain system and bilateral frontal inferior gyri , putatively involved in regulation of hunger and satiety . In hypersensitive FD , these activations occur at significantly lower distention pressures . In contrast to findings in normosensitivity , none of the components of the medial pain system were significantly activated BACKGROUND The diagnostic utility of 24-h oesophageal ambulatory pH monitoring in patients with functional dyspepsia has not been well established . AIMS We performed a prospect i ve study of oesophageal pH monitoring in patients with functional dyspepsia in order to assess whether a positive pH test might predict response to proton pump inhibitor therapy in a subset of functional dyspepsia patients . PATIENTS Forty Helicobacter pylori-negative functional dyspepsia patients ( 35 males and 5 females , mean age ( + /-S.E.M. ) of 54+/-2.4 years ) with predominantly unspecified dyspepsia subtype and normal distal oesophageal biopsies . METHODS All subjects were r and omised in a double-blind fashion to either omeprazole 20 mg/day or placebo daily for four weeks after 24-h pH monitoring . RESULTS Twenty-four-hour pH monitoring was abnormal in 9 of the 21 patients ( 43 % ) in the omeprazole group and 5/19 ( 26 % ) of the placebo group ( p = NS ) . Patients who reported symptomatic improvement on the Gastrointestinal Symptom Rating Scale were no more likely to have abnormal scores on pH monitoring than patients who did not have symptomatic response . CONCLUSIONS Although approximately one-third of functional dyspepsia patients will have abnormal profiles on 24-h ambulatory oesophageal pH monitoring , an abnormal score does not appear to predict response to proton pump inhibitor therapy in patients with unspecified functional dyspepsia Motilin‐receptor agonists are prokinetics ; whether they relieve the symptoms of functional dyspepsia is unknown . We aim ed to test the efficacy of the motilin agonist ABT‐229 in functional dyspepsia patients with and without delayed gastric emptying BACKGROUND AND AIMS Treatment of functional dyspepsia with acid inhibitors is controversial and it is not known if the presence ofHelicobacter pylori infection influences the response . METHODS After a complete diagnostic workup , 792 patients with functional dyspepsia unresponsive to one week of low dose antacid treatment were r and omised to two weeks of treatment with placebo , ranitidine 150 mg , omeprazole 10 mg , or omeprazole 20 mg daily . Individual dyspeptic and other abdominal symptoms were evaluated before and after treatment according to H pylori status . RESULTS The proportions of patients considered to be in remission ( intention to treat ) at the end of treatment with placebo , ranitidine 150 mg , omeprazole 10 mg , and omeprazole 20 mg were , respectively , 42 % , 50 % , 48 % , and 59 % in the H pylori positive group and 66 % , 73 % , 64 % , and 71 % in the H pylori negative group . In H pyloripositive patients , the therapeutic gain over placebo was significant for omeprazole 20 mg ( 17.6 % , 95 % confidence intervals ( CI ) 4.2–31.0 ; p<0.014 using the Bonferroni-adjusted p level of 0.017 ) but not for omeprazole 10 mg ( 6.8 % , 95 % CI −6.7–20.4 ) or ranitidine 150 mg ( 8.9 % , 95 % CI −4.2–21.9 ) . There was no significant therapeutic gain from active treatment over placebo in H pylori negative patients . Complete disappearance of symptoms and improvement in quality of life also occurred most frequently with omeprazole 20 mg and was significant in both H pylori positive and H pylori negative groups . The six month relapse rate of symptoms requiring treatment was low ( < 20 % ) in all groups . CONCLUSIONS Omeprazole 20 mg per day had a small but significant favourable effect on outcome in H pylori positive patients . The differential response in these patients may be explained by an enhanced antisecretory response in the presence of H pylori . The effect of weaker acid inhibition was unsatisfactory Prokinetic agents like itopride hydrochloride and mosapride citrate are commonly used in the management of functional dyspepsia . However , in a recently conducted international , multicentric study , efficacy of 3 different regimens of mosapride was shown to be comparable to placebo . The objective of this phase 4 r and omised , double blind , prospect i ve study was to compare the efficacy and safety of ganaton ( itopride hydrochloride ) and mosapride citrate in the management of functional dyspepsia among patients attending the gastroenterology outpatient department of a tertiary care hospital . Ganaton 50 mg or mosapride citrate 5 mg three times daily before meals for a period of 2 weeks was administered orally . Thirty functional dyspepsia patients in each group ( total = 60 ) were r and omised to receive itopride hydrochloride or mosapride citrate treatment for 2 weeks . In itopride versus mosapride groups , global efficacy as judged by patients was excellent in 17 versus 9 ( p < 0.05 ) and poor in 0 versus 3 ( p < 0.05 ) . In itopride versus mosapride group global efficacy as judged by physician was excellent in 24 ( 80 % ) versus 15 ( 50 % ) and poor in 0 ( 0 % ) versus 3 ( 10 % ) patients respectively . The global efficacy was rated as excellent to good in significantly ( p < 0.05 ) more number of patients in itopride ( 93.3 % ) group as compared to mosapride ( 63.33 % ) group . None of the patients reported any adverse events with itopride treatment . In the mosapride group 5 patients ( 16.7 % ) reported adverse events . Two patients ( 6.7 % ) were withdrawn from mosapride treatment due to adverse events . The physician rated global tolerability ofitopride versus mosapride treatment as excellent in 23 ( 76.7 % ) versus 8 ( 26.7 % ) ( p < 0.05 ) and poor in 0 ( 0 % ) versus 6 ( 20 % ) patients respectively . It may be concluded that ganaton ( itopride hydrochloride ) is superior in efficacy and safety over mosapride citrate in the management of functional dyspepsia BACKGROUND & AIMS Levosulpiride is a benzamide derivate D(2 ) dopamine antagonist with prokinetic activity that can accelerate gastric emptying and reduce discomfort in response to gastric distention . The aim of the study is to compare the clinical efficacy of levosulpiride and cisapride in patients with dysmotility-like functional dyspepsia . METHODS In a exploratory pilot study performed as a multicenter , r and omized , double-masked trial , the effects of 8 weeks of treatment with either levosulpiride , 25 mg , 3 times daily ( n = 69 ) or cisapride , 10 mg , 3 times daily ( n = 71 ) were compared . Individual symptoms ( pain/discomfort , fullness , bloating , early satiety , and nausea/vomiting ) , global symptom score , effect on health-related quality of life ( HRQoL ) , and anxiety-state and anxiety-trait were evaluated . Adverse events also were recorded . RESULTS Both levosulpiride and cisapride improved dyspeptic symptoms and decreased total symptom score ( 79.9 % and 71.3 % , respectively ) ; no significant statistical difference between treatments was found ( P = 0.07 for total symptom score ) . HRQoL improved similarly after both treatments , whereas no change was observed in anxiety . Medication-related adverse effects were present in 13 of 69 patients ( 18.8 % ) in the levosulpiride group and 8 of 71 patients ( 11.3 % ) in the cisapride group . Significantly more ( P = 0.03 ) patients treated with cisapride had to ab and on the trial because of side effects . CONCLUSIONS Levosulpiride is at least as effective as cisapride in the treatment of dysmotility-like functional dyspepsia BACKGROUND AND AIM Although mucosal protective agents have been used frequently for treatment of symptomatic gastritis , there has been no well-controlled study of functional dyspepsia . The aim of this study was to assess the efficacy of a 4-week treatment with rebamipide for the relief of overall dyspeptic symptoms and the improvement in quality of life from an untreated baseline in Japanese patients with functional dyspepsia . METHODS In a double-blinded , r and omized , placebo-controlled , single-center study , 81 patients with functional dyspepsia were recruited and treated with rebamipide ( 100 mg , t.i.d . ) or placebo for 4 weeks . Symptoms were assessed at baseline and at the end of the study period by a symptom question naire . Quality of life was evaluated by the QPD 32 . RESULTS Data was analyzed for symptoms from 38 patients who received rebamipide and 33 patients who received placebo treatment . Overall symptoms were significantly improved in both the rebamipide and placebo treatment groups from the untreated baseline after 4 weeks of treatment , and the mean changes in overall symptoms were not significantly different between the groups . However , the improvement in symptom score was significantly greater in the treatment arm than in the placebo arm for three items , which were bloating , belching , and pain or discomfort that was relieved after a meal . Regarding quality of life , social restriction and pain intensity were significantly improved in the rebamipide treatment group in per- protocol analysis ( P = 0.048 and P = 0.031 , respectively ) . CONCLUSIONS Although rebamipide was not significantly better than placebo in reducing overall symptoms by 4 weeks ' treatment , it may partially improve the symptoms . It may also be beneficial in improvement of quality of life in Japanese patients with functional dyspepsia BACKGROUND The efficacy of unselected monoamine reuptake inhibitors ( tricyclic antidepressants ) in the treatment of patients with functional gastrointestinal disorders ( FGD ) has not been convincingly demonstrated . We investigated the efficacy of an antidepressant ( mianserin ) with a different receptor profile ( combined 5-hydroxytryptamine-2 + 3 and alpha-2 antagonist ) in FGD . METHODS After excluding patients with psychopathology and initial placebo responders from the study , eligible patients ( n = 49 ) were r and omized to 7 weeks of double-blind treatment with either mianserin , 120 mg/day , or placebo . Efficacy was assessed by using observer-completed ratings , the Global Improvement Scale , and patient self-ratings , Visual Analog Scale , and Disability Scales . RESULTS Patients taking mianserin reported less abdominal pain , symptoms of abdominal distress , and functional disability than those given placebo ( p < 0.001 ) . The efficacy was significant across different lengths of illness periods and types of functional disorder . There was no major change 4 weeks after tapering . CONCLUSION Mianserin may be an effective and well-tolerated pharmacologic short-term treatment for functional gastrointestinal disorders in patients with no clinical evidence of psychopathology Background : Histamine 2‐receptor antagonists were used as a first therapy against functional dyspepsia . However , few clinical studies with famotidine for functional dyspepsia have been reported OBJECTIVE Tricyclic antidepressants in low doses are widely used in the therapy of patients with functional gastrointestinal disorders , yet the mechanism(s ) of action of these drugs in these disorders is not known . In the current study , we sought to determine in a group of patients with functional dyspepsia and associated poor sleep how amitryptiline affects digestive symptoms , perceptual responses to gastric distension , and subjective and objective measures of sleep . METHODS Patients were r and omized to 4 wk of amitryptiline 50 mg taken at bedtime versus placebo . There was a 3-wk washout phase , followed by a cross-over to the alternate treatment . Perceptual sensitivity to gastric distention and sleep EEG were recorded at the end of each treatment period . Diaries of symptoms were maintained throughout . RESULTS Seven of seven patients reported significantly less severe gastrointestinal symptoms after 4 wk on amitryptiline compared to placebo . Five of seven patients had evidence for altered perception of gastric balloon distension during placebo . However , the subjective symptom improvement on amitryptiline was not associated with a normalization of the perceptual responses to gastric distension . Baseline sleep dysfunction in the form of reduced sleep efficiency , increased arousal , or abnormal amounts of REM sleep was found in all seven patients . Amitryptiline significantly reduced absolute and relative amounts of REM sleep , but had no effect on sleep parameters related to nonregenerative sleep . CONCLUSION The beneficial effect of low dose amitryptiline seen in functional dyspepsia is not related to changes in perception of gastric distension , or to measures of arousal from sleep . An increased tolerance to aversive visceral sensations may play a role in the therapeutic effect The efficacy of H2‐receptor antagonists in functional dyspepsia is equivocal and the therapeutic place of proton pump inhibitors in functional dyspepsia is unknown The efficacy of several prokinetic drugs on dyspeptic symptoms and on gastric emptying rates are well‐established in patients with functional dyspepsia , but formal studies comparing different prokinetic drugs are lacking |
12,836 | 17,785,279 | RESULTS MRI is highly accurate in diagnosing meniscal and anterior cruciate ligament ( ACL ) tears .
It is the most appropriate screening tool before therapeutic arthroscopy .
It is preferable to diagnostic arthroscopy in most patients because it avoids the surgical risks of arthroscopy . | PURPOSE Magnetic resonance imaging ( MRI ) is of great aid in the diagnosis of knee lesions .
Most diagnostic studies comparing MRI and arthroscopy have shown good diagnostic performance in detecting lesions of the menisci and cruciate ligaments .
Nevertheless , arthroscopy has remained the reference st and ard for the diagnosis of internal derangements of the knee , against which alternative diagnostic modalities should be compared . | Abstract Eight patients with ganglion cysts arising from the cruciate ligaments of the knee joint underwent arthroscopic excision after the MR examination . The MR findings , clinical features and arthroscopic findings were evaluated comparatively . Résumé Après un examen IRM , huit patients présentant des kystes se développant à partir des ligaments croisés du genou , ont subi une excision arthroscopique . Les résultats de l’examen IRM , de l’examen clinique et de l’examen arthroscopique ont été comparés Magnetic resonance imaging ( MRI ) was used to diagnose acute and chronic intraarticular knee pathology in 23 knees . The results were compared with arthroscopic findings of meniscal , ligamentous , and articular cartilaginous pathology using a double-blind prospect i ve protocol . The overall accuracy for meniscal tears was 78 % , with a sensitivity of 88 % and a specificity of 72 % ; for cruciate ligaments , MRI was 82 % accurate , with a sensitivity of 67 % [ anterior cruciate ligament ( ACL ) only ] and a specificity of 86 % . In select clinical situations , MRI of the knee is a useful diagnostic tool Amongst a series of 332 patients undergoing a prospect i ve evaluation of the influence of magnetic resonance imaging ( MRI ) on diagnosis and outcome , arthroscopic correlation became available in 92 knees ( 91 patients ) . The MRI report , the arthroscopic findings and the patient 's case notes were review ed by a consensus panel . With respect to the menisci and cruciate ligaments , the formal radiological report was at variance with the arthroscopic findings in 22/349 sites where there had been no previous surgery ( 10 medial meniscus , six lateral meniscus and six anterior cruciate ligament ) . 12 of these 22 errors were considered , on review , to be genuine MRI errors . However , considerable controversy remains as to whether the other 10 " errors " were true or false . There are several factors which contribute to such controversy . These include technically difficult arthroscopies , delays between MRI and arthroscopy , and ambiguities in the wording of both the referral letter and the radiological report . These factors should be considered when evaluating the diagnostic performance of both MRI and arthroscopy A prospect i ve double-blind study was undertaken to evaluate the usefulness of magnetic resonance imaging in the accurate interpretation of pathological intra-articular changes in the knee . Forty-seven patients who were scheduled to have arthroscopy and three patients who wer to have arthrotomy volunteered for magnetic resonance imaging preoperatively . The radiologists had no clinical or roentgenographic information about the patients before the evaluation of the magnetic resonance images , and the radiologists ' interpretations were unknown to the surgeon before the arthroscopy or arthrotomy was done . Our important observations were limited to the findings in the menisci and in the anterior cruciate ligament . Magnetic resonance imaging had a positive predictive value of 75 per cent , a negative predictive value of 90 per cent , a sensitivity of 83 per cent , and a specificity of 84 per cent for pathological findings in the menisci . For complete tears of the anterior cruciate ligament , the positive predictive value was 74 per cent ; the negative predictive value , 70 per cent ; the sensitivity , 61 per cent ; and the specificity , 82 per cent . We believe that magnetic resonance imaging , when combined with clinical and roentgenographic examination , provides the most accurate non-invasive source of information that is currently available for pathological findings in the menisci and in the anterior cruciate ligament In a prospect i ve study , magnetic resonance imaging was performed before arthroscopy for all patients ( n = 121 ) with a meniscal tear ( n = 125 ) . Criteria of the study were stable cruciate and collateral ligaments , absence of pathologic radiographic findings , and absence of prior surgical interventions of the involved knee joint . In 43 knees ( 34 % ) , the clinical diagnosis of a meniscal tear was discarded because of the results of the magnetic resonance imaging examination . Synovitis was diagnosed in 16 patients ( 13 % ) , articular cartilage damage in 10 patients ( 8 % ) , bone bruise injuries in 10 patients ( 8 % ) , osteochondritis dissecans in 3 patients ( 2 % ) , disruption of the inner layer of the medial collateral ligament in 3 patients ( 2 % ) , and osteonecrosis in 1 patient . The use of magnetic resonance imaging in establishing diagnosis of disorders of the knee joint altered treatment in a significant proportion of patients . Magnetic resonance imaging should be done before arthroscopy of the knee in all cases in which the clinical diagnosis has been reduced to a suspected meniscus injury In children , compulsory arthroscopy for hemarthrosis after knee trauma is not justified because ligamentous and meniscal damage is rare . In a prospect i ve study , we analyzed the diagnostic value of radiography , magnetic resonance imaging ( MRI ) , and arthroscopy in 51 patients up to 14 years of age with acute knee trauma . Plain radiography revealed 16 osseous lesions ( 5 metaphyseal , 3 patellar , 4 physeal fractures , 3 avulsions of the tibial spine , and 1 osseous ligamentous tear ) . In 29 patients , the cause of hemarthrosis remained unclear . All patients were evaluated by MRI . A diagnosis could be assigned to all 29 patients . MRI demonstrated lesions in 38 patients . In addition , the following lesions were discovered : 8 patellar dislocations , 13 bruises , 1 rupture of the anterior cruciate ligament , 1 osteochondritis dissecans , and 13 joint effusions . In 13 patients , MRI was followed by arthroscopy to confirm the diagnosis . Both , MRI and arthroscopy missed two osteochondral fractures . In addition , three chondral lesions were not picked up by MRI . MRI is a reliable tool for assessing the extent of knee lesions in children OBJECTIVE To compare partial flexion true sagittal ( FS ) magnetic resonance ( MR ) images with extension sagittal oblique ( ESO ) MR images with regard to delineation of the anterior cruciate ligament ( ACL ) in the knee . DESIGN To establish the appropriate degree of flexion of the knee joint , two human cadaveric knee joints were used as a supplementary technique . FS and ESO images then were performed in 17 knees with an intact ACL and six knees with a torn ACL . In 22 of the 23 knees in which the MR diagnosis of intact or torn ACL corresponded to that derived from arthroscopy , the paired MR images were rated by a three-point scale . RESULTS FS images were rated superior to ESO images in 53 % , 41 % and 47 % of cases with regard to femoral attachment sites , midportions and tibial attachment sites of intact ACLs , respectively . FS images allowed better assessment of disrupted ACLs and residual ligamentous structures . Overall the FS images were either equal to or better than the ESO in the majority of cases . CONCLUSION FS images are useful when the ACL is not well visualized in initial ESO images OBJECTIVES The aim of the study reported here was to investigate whether the use of magnetic resonance imaging ( MRI ) impacts on the clinical management of patients presenting with chronic knee problems , reduces costs , and improves patient outcome . METHODS A single-center r and omized controlled trial was conducted . Patients attending with knee problems in whom surgery was being considered were r and omized either to investigation using an MRI scan or to investigation using arthroscopy . The study investigated benefits in terms of avoidance of surgery and patient health-related quality of life ( using SF-36 and EQ-5D ) . Costs were assessed from the perspectives of the National Health Service and patients . All analyses were by intention to treat . RESULTS The trial recruited 118 patients . No statistically significant differences were found between groups in terms of health outcome . However , the use of MRI was associated with a positive diagnostic/therapeutic impact : a significantly smaller proportion of patients in the MRI group underwent surgery ( MRI = 0.41 , No-MRI = 0.71 ; p value = .001 ) . There was a similar mean overall cost for both groups . CONCLUSIONS The use of MRI in patients with chronic knee problems , in whom surgery was being considered , did not increase costs overall , was not associated with worse outcomes , and avoided surgery in a significant proportion of patients A prospect i ve and retrospective study was undertaken to compare the accuracy of magnetic resonance imaging ( MRI ) with clinical examination in diagnosing meniscal and anterior cruciate ligament ( ACL ) tears . Pathological findings were then confirmed during arthroscopy . One hundred fifty-four patients clinical ly diagnosed with a meniscal or ACL tear who ultimately had arthroscopic knee surgery were evaluated ; 100 patients underwent clinical examination followed by MRI , and 54 underwent clinical examination alone . The presence or absence of meniscal and ACL tears was confirmed during arthroscopy . The accuracies of clinical examination and MRI were compared for the 100 patients who underwent both clinical examination and MRI . The accuracy of MRI was 75 % for medial meniscal tears , 69 % for lateral meniscal tears and 98 % for ACL tears . The accuracy of clinical examination was 82 % for medial meniscal tears , 76 % for lateral meniscal tears and 99 % for complete tears of the ACL . Furthermore , the accuracy of clinical examination for the 54 patients who underwent clinical examination alone was not significantly different from the accuracy of clinical examination in the 100 patients who also underwent MRI . There was no significant difference between the accuracy of clinical examination and MRI in the diagnosis of meniscal and ACL tears and , overall , MRI contributed to treatment in only 16 of 100 cases . Based on these findings , we feel that MRI , except in certain circumstances , is an expensive and unnecessary diagnostic test in patients with suspected meniscal and ACL pathology Rapidly progressing medical technology sometimes obscures the importance of history and physical examination . This study was design ed to assess the value of MRI and clinical examination in the diagnosis of ligamentous and meniscal knee injuries in comparison with arthroscopic findings . In the year 2003 - 2004 , we conducted a prospect i ve , single blind study to assess ligamentous and meniscal injuries of the knee in patients with acute knee trauma . The mean age was 27.9 years . The sex distribution was 81.4 % male and 18.6 % female ; 42.9 % of injuries affected the right knee and 57.1 % the left knee . All the included patients were ordered a MRI , executed in five separate centres . All patients underwent arthroscopy by the author . Arthroscopic findings were the diagnostic reference . Clinical examination was accurate in 91.4 % , and MRI in 88.5 % of anterior cruciate ligament injuries . For posterior cruciate ligament injuries , clinical accuracy was 100 % and MRI 94.6 % . Clinical examination was accurate in 96.9 % and MRI in 85.9 % of medial meniscal injuries . For lateral meniscus injuries , clinical accuracy was 85.4 % and MRI 73.8 % . MRI findings showed the lowest correlation with arthroscopic findings in lateral meniscus injuries ( r = 0/47 ) . Clinical diagnostic performance was poorest in case of combined cruciate ligament and meniscal injuries . We found an excellent correlation between MRI and clinical findings . However , when MRI is normal , high clinical suspicion and a skilled clinical examination are more reliable A blind and prospect i ve study was conducted to assess the accuracy of magnetic resonance imaging ( MRI ) for diagnosing patellar cartilage lesions . Thirty-three consecutive patients undergoing knee arthroscopy were examined by MRI prior to surgery . Imaging was performed in the axial plane on a 1.5-Tesla unit with spinecho and gradient-echo T1 and T2 sequences . The MRI and arthroscopic data were compared using a four- grade classification and a patellar map which divided the patellar surface into four quadrants . The overall sensitivity of MRI was 84.7 % and the specificity 97.2 % . The same pit-fall led to two MRI false positives . A perfect correlation of grading was obtained in 76.5 % . When discordance was found , the tendency with MRI was commonly to underestimate the grade of the lesions . The MRI accuracy was high in this study in spite of a high rate of low- grade lesions which are difficult to assess . Related criteria for cartilage assessment with MRI and arthroscopy are suggested for further studies OBJECTIVE Meniscal resection decreases the ability of the meniscus to evenly distribute forces placed on it . These forces are oriented centrifugally on the meniscus by normal weight-bearing and are distributed by circumferentially oriented fibers . This alteration may predispose the knee to radial tears after surgery . SUBJECTS AND METHODS One of three musculoskeletal radiologists prospect ively interpreted 100 consecutive postoperative MRI examinations of the knee . A prospect i ve MRI report was generated for the referring orthopedic surgeon , and prospect i ve MRI interpretations were correlated with arthroscopic findings ( n = 63 ) . MRI examinations on those patients who underwent second-look arthroscopy were retrospectively review ed by three musculoskeletal radiologists who reached a consensus on the prevalence of new postoperative meniscal radial tears . MRI criteria for radial tear diagnosis were used as outlined by Tuckman et al. : truncation , abnormal morphology , lack of continuity , absence of the meniscus , or any combination of those criteria on one or more MR images . An additional criterion used was abnormal increased signal in that area on T2-weighted images . RESULTS Thirty-two of the 100 patients had meniscal radial tears on prospect i ve MRI interpretations . In 29 of these 32 patients , second-look arthroscopy confirmed meniscal radial tears in the areas described on the MRI examinations . Five additional radial tears were shown on second-look arthroscopy that were not seen on prospect i ve MRI interpretations . Two of those additional five radial tears were seen on consensus retrospective MRI review . CONCLUSION In this study , a 32 % prevalence of meniscal radial tears in the postoperative knee was present on prospect i ve MRI interpretations as opposed to a reported 14 % prevalence in the nonoperated knee . Meniscal resection decreases the ability of the meniscus to evenly distribute forces placed on it . This circumstance may increase the prevalence of meniscal radial tears in the postoperative knee . New meniscal radial tears are common in patients presenting with pain after knee surgery A double blind prospect i ve study involving fifty patients was performed to assess the diagnostic accuracy of knee MR Imaging using a 0.3 Tesla low field strength scanner . The study compared MR Imaging with arthroscopy . The overall accuracy found for the detection of meniscal tears was 92 % and cruciate ligament tears 95 % . These results compare favourably with other diagnostic modalities including knee arthroscopy . MR Imaging is good at showing meniscal lesions , especially cleavage tears , though some bucket-h and le tears produced no MR abnormality . MR Imaging is very accurate at demonstrating complete cruciate ligament tears . Partial cruciate ligament tears often produced no positive MR findings and in no patients could any features be found to indicate ligamentous laxity Results of a year-long prospect i ve audit of all arthroscopies of the knee in one NHS Trust hospital indicate that selective magnetic resonance imaging ( MRI ) would be cost-effective in up to 40 % of patients . However , to achieve such savings , at least 14 % of patients who would otherwise need diagnostic arthroscopy would need to be excluded from surgery , the cost of MRI must be low , and the success rate of interpreting the scans should be known OBJECTIVE To compare radiographic , magnetic resonance imaging ( MRI ) , and outpatient direct arthroscopic evaluation of cartilage in patients with osteoarthritis ( OA ) of the knee . METHODS Thirty-three patients with OA of the knee were evaluated by plain weight bearing radiographs and arthroscopy using a 1.9 mm arthroscope under local anesthesia . Sixteen of these patients also had MRI of the knee performed . Knee compartments were evaluated using AP weight bearing and lateral radiographs of the knee . MRI and outpatient arthroscopic grading of cartilage were performed within 2 weeks of the plain radiographs . The MRI and arthroscopic evaluations were performed independently and were grade d without knowledge of the other . RESULTS In patients in whom plain radiographs , MRI , and arthroscopy were compared , the plain radiographs and MRI significantly underestimated the extent of cartilage abnormalities . There was a moderate correlation between imaged cartilage scores and the arthroscopy scores ( Pearson correlation coefficient = 0.40 ) . The arthroscopic scores were reproducible with good intra and inter-observer reliability . The arthroscopic procedure was well tolerated and actually preferred over the MRI by the majority of patients . No significant complications were noted as a result of arthroscopy . CONCLUSIONS Our results indicate that outpatient arthroscopic evaluation is a useful method in evaluating surface cartilage abnormalities and is more sensitive in detecting these abnormalities than either plain radiographs or MRI . Outpatient arthroscopic evaluation of cartilage appears to be a safe , sensitive , and a well tolerated tool for evaluating patients with OA of the knee and may prove to be particularly useful in evaluating response to therapeutic interventions OBJECTIVE After surgical resection or repair of a torn meniscus , the healed area may have areas of abnormal signal intensity on MR images . Consequently , routine MR imaging is not reliable for detecting recurrent meniscal tears . As a result , we studied the efficacy of MR imaging with intraarticular contrast material ( MR arthrography ) for detecting recurrent tears of the meniscus . SUBJECTS AND METHODS Thirty-seven patients who previously had a meniscal tear treated by either meniscal resection or repair had conventional MR imaging and MR arthrography with 40 - 50 ml of a 1:100 solution of gadopentetate dimeglumine in saline . All patients had arthroscopy shortly after the MR studies . Follow-up arthroscopic surgery was performed within an average of 6.6 weeks after the MR arthrograms . The routine MR images and MR arthrograms were review ed separately and r and omly , and these results were compared with the arthroscopic findings . Meniscal morphology , signal intensity , and the presence of joint fluid tracking into recurrent tears were evaluated . RESULTS The overall accuracy in diagnosing recurrent meniscal tears in the post-operative meniscus was 66 % when conventional MR imaging was used and 88 % when MR arthrography was used . In patients who had only minimal meniscal resection , both methods had an accuracy of 89 % . In patients who had more extensive meniscal resection , accuracy was 65 % with conventional MR imaging and 87 % with MR arthrography . In four patients who had only a small meniscal remnant , the accuracy was 50 % with routine MR imaging and 100 % with MR arthrography . On conventional MR images , the presence of an effusion tracking into a meniscal tear had a sensitivity and positive predictive value of 90 % for detection of recurrent meniscal tears ; however , the sensitivity was only 41 % . CONCLUSION Our results show that the sensitivity of MR imaging in detecting meniscal tears after surgery varies with the extent of the resection . Sensitivity was considerably improved when intraarticular contrast material was used . MR arthrography should be considered as an alternative to arthroscopy in patients who have had resection or repair of the meniscus OBJECTIVE We attempted to determine the potential cost savings of prearthroscopic knee MR imaging examinations . SUBJECTS AND METHODS This prospect i ve study involved 50 consecutive patients . The patients met the surgical-indications-for-monitoring-appropriateness criteria for knee arthroscopy and underwent MR imaging of the knee before arthroscopy . For all patients , we compared MR imaging and arthroscopic findings . On the basis of a cost of $ 1000 for each MR imaging examination and $ 4000 for each diagnostic arthroscopy , we decided that cost-effective MR imaging would require 25 % true negativity . RESULTS The respective sensitivities and specificities of MR imaging of the knee were 100 % and 90 % for revealing anterior cruciate ligament interruption , 100 % and 84 % for revealing posterior cruciate ligament tears , 90 % and 97 % for revealing medial meniscal tears , 60 % and 100 % for revealing lateral meniscal tears , and 94 % and 93 % for revealing composite injury ( one or more of these abnormalities ) . With MR imaging examinations obtained before surgery , we found 21 ( 42 % ) of 50 arthroscopies to be unnecessary . CONCLUSION Despite stringent clinical criteria used in selecting patients for arthroscopy , 42 % of our patients could have been spared surgery on the basis of the anatomy revealed by MR imaging . Our study indicates that MR imaging obtained before arthroscopy of the knee can produce a savings of as much as $ 680 per MR imaging examination performed on the knee This prospect i ve r and omized clinical trial evaluated whether the use of radiofrequency energy ( RFE ) devices for soft-tissue ablation and coagulation cause thermal injury to bone . Fifty patients underwent one of three treatment modalities : electrocautery , monopolar RFE , or bipolar RFE . Preoperative and postoperative magnetic resonance imaging was compared to evaluate for evidence of osteonecrosis . Postoperative MRI of all patients did not reveal any osteonecrosis or subchondral edema . These findings indicate electrocautery , monopolar RFE , and bipolar RFE devices can be used safely for soft-tissue blation and hemostasis PURPOSE The purpose of this study was to compare the outcomes of mosaic-type osteochondral autologous transplantation ( OAT ) and microfracture ( MF ) procedures for the treatment of the articular cartilage defects of the knee joint in young active athletes . TYPE OF STUDY Prospect i ve r and omized clinical study . METHODS Between 1998 and 2002 , a total of 60 athletes with a mean age of 24.3 years ( range , 15 to 40 years ) and with a symptomatic lesion of the articular cartilage in the knee were r and omized to undergo either an OAT or an MF procedure . Only those athletes playing in competitive sports at regional or national levels were included in the study . Fifty-seven athletes ( 95 % ) were available for a follow-up . There were 28 athletes in the OAT group and 29 athletes in the MF group . The mean duration of symptoms was 21.32 + /- 5.57 months and the mean follow-up was 37.1 months ( range , 36 to 38 months ) , and none of the athletes had prior surgical interventions to the affected knee . Patients were evaluated using modified Hospital for Special Surgery ( HSS ) and International Cartilage Repair Society ( ICRS ) scores , radiograph , magnetic resonance imaging ( MRI ) , and clinical assessment . An independent observer performed a follow-up examination after 6 , 12 , 24 , and 36 months . At 12.4 months postoperatively , arthroscopy with biopsy for histologic evaluation was carried out . A radiologist and a pathologist , both of whom were blinded to each patient 's treatment , did the radiologic and histologic evaluations . RESULTS After 37.1 months , both groups had significant clinical improvement ( P < .05 ) . According to the modified HSS and ICRS scores , functional and objective assessment showed that 96 % had excellent or good results after OAT compared with 52 % for the MF procedure ( P < .001 ) . At 12 , 24 , and 36 months after surgery , the HSS and ICRS showed statistically significantly better results in the OAT group ( P = .03 ; P = .006 ; P = .006 ) . Younger athletes did better in both groups . No serious complications were reported . There was 1 failure in the OAT group and 9 in the MF group . The ICRS Cartilage Repair Assessment for macroscopic evaluation during arthroscopy at 12.4 months showed excellent or good repairs in 84 % after OAT and in 57 % after MF . Biopsy specimens were obtained from 58 % of the patients and histologic evaluation of repair showed better scores ( according to ICRS ) for the OAT group ( P < .05 ) . MRI evaluation showed excellent or good repairs in 94 % after OAT compared with 49 % after MF . Twenty-six ( 93 % ) OAT patients and 15 ( 52 % ) MF patients returned to sports activities at the preinjury level at an average of 6.5 months ( range , 4 to 8 months ) . Others showed a decline in sports activity level . CONCLUSIONS At an average of 37.1 months ( range , 36 to 38 months ) follow-up , our prospect i ve , r and omized , clinical study in young active athletes under the age of 40 has shown significant superiority of OAT over MF for the repair of articular cartilage defects in the knee . We found that only 52 % of MF athletes could return to sports at the preinjury level . Limitations of our study included a small number of athletes and a relatively short ( 3-year ) follow-up . A long-term follow-up is needed to assess the durability of articular cartilage repair using these methods in young active athletes . LEVEL OF EVIDENCE Level I , Therapeutic study , r and omized controlled trial , significant difference ( a ) The role of magnetic resonance tomography ( MRI ) for the diagnosis of chondral lesions of the knee joint is still unclear . The sensitivity of the method ranges from 15 % to 96 % . The scope of our daily experiences showed that there were considerable deviations between the tomographical and arthoscopical results , which vary from the results of experimental studies . Therefore we have conducted a prospect i ve study to investigate the question of how MRI can replace arthroscopy ( ASC ) in the diagnosis of cartilage damages in the scope of daily routine . All 195 patients included in this study received a magnetic resonance tomography followed by an arthroscopy . A clear diagnosis of supposition had to be determined before the magnetic resonance tomography . The patients were divided into 3 Groups . Group A ( n = 86 ) received a st and ard Military Hospital Ulm ( MH ) MRI — sagittal STIR TSE and PD TSE , coronal and transversal T2 FFE ( TR=660 ms , TE=18 ms , FA=30 ° , 512 matrix ) . In addition , one sub-Group , AK ( n = 21 ) was examined with a special cartilage sequence of the cartilage fs T1 W FFE . Neither patients in Group AK nor in Group A as a whole received any contrast medium . Group B ( n = 88 ) was examined with an alternate MRI protocol ( Radiological Joint Practice , Neu-Ulm — sagittal T1 SE , T2 SE and T2 FLASH ( TR=608 ms , TE=18 ms , FA=20 ° , 256 matrix ) , coronal PD fs ) , employing gadolinium as a contrast medium . 156 cartilage lesions were found arthroscopically . In Group A the sensitivity was 33 % , the specificity 99 % , and the positive and negative prediction values 75 % and 98 % respectively . Group B reached a sensitivity of 53 % and a specificity of 98 % . The positive prediction value was 48 % and the negative was 98 % . Group AK showed a sensitivity of 38 % and specificity of 98 % ; the positive and negative prediction values came to 50 % and 97 % respectively . In conclusion , our results indicate that the MRI examination techniques recommended in the literature at present are not able to replace the ASC for the diagnosis of cartilage damages of the knee joint . In view of the high specificity ( 97%–99 % ) and the high negative prediction value ( 97%–98 % ) , MRI is suitable for the exclusion of cartilage lesions . For a negative MRI associated with a cartilage injury , a cautious attitude towards an operative cartilage treatment is therefore justified . Because the MRI can not replace the ASC for diagnostic of cartilage damage , the ASC still has to be seen as the method of choice for the evaluation of cartilage damage We compared the findings of low-field MRI of the knee with those of subsequent arthroscopy . In a double-blind set-up , 47 patients with knee joint injuries were enrolled . Two radiologists independently interpreted the MRI examinations and consensus was obtained in case of discrepancy . Arthroscopy was performed without knowledge of the MRI findings . The accuracy rates of MRI for evaluating the medial meniscus , lateral meniscus and anterior cruciate ligament were 77 % , 91 % and 96 % , respectively , when arthroscopy was considered the " golden st and ard " . When MRI was considered the st and ard , the figures for arthroscopy were 74 % , 91 % and 96 % . MRI found the indication for treatment in 18 of 21 patients who were treated at the arthroscopy . In 17 patients , neither MRI nor arthroscopy detected any lesion . In the remaining 9 patients , MRI demonstrated a lesion , but no lesion was found at the subsequent arthroscopy . Our conclusion is that low-field MRI can be used as a first-line diagnostic examination in patients with suspected meniscus or cruciate ligament injuries and thus a substantial number of negative diagnostic arthroscopies can be avoided PURPOSE With the help of molecular markers , it has become possible to quantify cartilage repair and degradation in joints . In this study , we attempt to determine whether or not molecular markers in synovial fluid can be helpful in defining the repair process following autologous chondrocyte implantation ( ACI ) . TYPE OF STUDY As part of a prospect i ve clinical pilot study , 17 patients were evaluated before , as well as 6 weeks , 3 , 6 , and 12 months after the ACI . A synovial analysis was performed and molecular markers for bone and cartilage metabolism were determined . METHODS A number of parameters , including pyridinium crosslink ( PY ) , deoxypyridinolin ( DPD ) , n-telopeptide ( NTX ) from type I collagen , MMP-1 , MMP-3 ; TIMP-1 , PICP , proteoglycan , and YKL-40 were analyzed . The levels were referenced to the total protein concentration of the synovial fluid . The synovial analyses were compared with clinical parameters ( Larson score ) and magnetic resonance imaging ( MRI ) examinations . RESULTS The analysis of the data revealed differing trends for the various synovial markers over time . The most remarkable marker was found to be DPD , which increased continuously between surgery and week 12 , only to disappear after the repair process had ceased 1 year after surgery . All molecular markers for cartilage degradation increased initially after surgery and dropped off below the original levels 3 to 6 months later . CONCLUSIONS The evaluation revealed that the determination of marker levels can provide valuable information regarding the metabolism of bone and cartilage in a joint . They seem to provide a method for monitoring the repair process associated with the various treatment forms for chondral lesions We made a prospect i ve study of 58 patients with suspected internal derangement of the knee . They were examined by magnetic resonance imaging using 3-D gradient echo intermediate-weighted studies before having an arthroscopy . The preoperative clinical assessment was found to have a diagnostic sensitivity of 77 % and a specificity of 43 % , compared with 100 % and 63 % respectively for magnetic resonance imaging . Comparison of magnetic resonance imaging and arthroscopy confirmed the accuracy of magnetic resonance imaging in the diagnosis of internal derangement but the results for articular cartilage lesions were much less good , with a sensitivity of only 18 % but a specificity of 100 % . Acceptance of the magnetic resonance imaging findings could have result ed in a 29 % reduction in the number of arthroscopies without missing any significant meniscal lesion A prospect i ve audit of 321 patients ( 325 knees ) placed on the waiting list for arthroscopy revealed an accuracy of the preoperative diagnosis of 57 % . The accuracy of consultants was 71 % and the other grade s of staff was 49 % . The operation treated a pathological lesion and was considered to be therapeutic in 154 knees ( 47 % ) ; an operation was more likely to be therapeutic when the preoperative diagnosis was correct ( 132 knees ) than when the diagnosis was incorrect ( 22 knees ) . Attention to establishing an accurate preoperative diagnosis and close supervision of the waiting lists by consultants will reduce the number of non-therapeutic arthroscopies |
12,837 | 23,440,791 | No significant differences were seen with regard to the development of ascites , encephalopathy , hepatocellular carcinoma , or the need for liver transplantation .
Adverse effects tended to be more common in the interferon recipients ; the ones that were significantly more common included hematologic complications , infections , flu-like symptoms , and rash .
In this scenario , retreatment with interferon did not appear to provide significant clinical benefit and , when only the trials at low risk of bias were considered , retreatment for several years may even have increased all-cause mortality .
Such treatment also produced adverse events .
On the other h and , the treatment did result in improvement in some surrogate outcomes , namely sustained viral responses and histologic evidence of inflammation . | BACKGROUND The widely-accepted treatment outcome for chronic hepatitis C is the sustained viral response ( that is , no measurable viral RNA in blood six months after treatment ) .
However , this surrogate outcome ( as well as the previously employed biochemical and histologic ones ) has never been vali date d. This situation exists because there are very few r and omized clinical trials that have used clinical events ( mortality or manifestations of decompensated cirrhosis ) as outcomes , because those clinical events only occur after many years of infection .
Patients in whom initial therapy fails to produce sustained viral responses do become potential c and i date s for retreatment ; some of these individuals are not c and i date s for ribavirin or protease inhibitors and consideration could be given to retreatment with interferon alone .
OBJECTIVES To assess the benefits and harms of interferon monotherapy retreatment in chronic hepatitis C patients and to vali date the currently employed surrogate outcomes in this group of patients . | Interferon has been shown to be an effective treatment for some patients with chronic hepatitis C. In this study , the value of retreatment of nonresponders to interferon was investigated . Thirty-eight patients with hepatitis C virus (HCV)-RNA-positive chronic hepatitis C virus (HCV)-RNA-positive chronic hepatitis C who had been treated with betainterferon but still showed an alanine aminotransferase ( ALT ) level>50 KU upon completion of therapy were retreated with alpha-interferon . Eight patients ( 21.1 % ) had normalization of ALT levels after interferon retreatment were studied . Of 16 patients with transient HCV-RNA negativity 1 month after the initial interferon therapy , 7 ( 43.8 % ) had a complete response , with normalization of ALT levels and undetectable HCV-RNA , more than 6 months after interferon retreatment . On the other h and , of the 22 patients with HCV-RNA activity 1 month after the initial interferon therapy , only 1 ( 4.5 % ) had a complete response . Multivariate analysis , using a multiple logistic model , indicated that a complete response to readministration of interferon was most strongly correlated to transient negative conversion for HCV-RNA after the initial course of treatment BACKGROUND AND AIM Interferon-alpha treatment of chronic hepatitis C is beneficial in only 20 - 30 % of patients . This study evaluates if combination therapy with Interferon-alfa plus ribavirin is effective in inducing a response in patients who did not respond to , or relapsed after , a st and ard Interferon-alfa treatment . PATIENTS AND METHODS A total of 88 patients , 49 non-responders and 39 relapsers to previous Interferon-alfa therapy , were r and omized to receive either natural Interferon-alfa ( 6 MU t.i.w . ) plus ribavirin ( 1000 mg/daily ) or natural Interferon-alfa alone ( 6 MU t.i.w . ) for 6 months . All were followed for 12 months after stopping therapy . Serum aminotransferase levels were assessed monthly and HCV RNA was evaluated by RT-PCR ( Amplicor , Roche ) at end of therapy and the end of follow-up . RESULTS After treatment , a higher response rate defined as return to normal of aminotransferases and absence of serum HCV RNA was observed among patients treated with Interferon-alfa-ribavirin : 4/28 ( 14 % ) vs 1/21 ( 5 % ) non-responder patients and 9/19 ( 47 % ) vs 5/20 ( 25 % ) in the relapsers group . At the end of follow-up , a sustained response was found only in the combination treatment group : 4 % and 32 % in non-responder and relapser patients , respectively . CONCLUSIONS Our results suggest that retreatment with natural Interferon-alfa plus ribavirin is more effective than Interferon-alfa alone in increasing the response rate in patients with chronic hepatitis C who relapse after a previous st and ard IFN treatment whereas it is less effective in non-responder patients The aim of this study was to eluci date indicator of interferon ( IFN ) therapy for reducing hepatocellular carcinoma ( HCC ) in chronic hepatitis C patients without eradicating hepatitis C virus ( HCV ) RNA during IFN therapy . Inclusion criteria were biopsy-proven chronic hepatitis or liver cirrhosis , IFN period for more than 1.5 years and persistently positive HCV-RNA during IFN therapy . Two hundred thirty-six patients satisfied above criteria were treated with IFN for 1.5 - 5 years ( median 1.8 years , mean 2 years ) . Mean age was 55.1 years and male was 145 ( 61 % ) . Eighty-one ( 34 % ) patients had severe fibrosis of the liver . These patients were prospect ively monitored about HCC after the termination of IFN therapy . We regarded biochemical response ( BR ) as normalization of serum aminotransferase and alpha-fetoprotein for more than 1 year during IFN therapy . Cumulative rate of development of HCC after the termination of IFN therapy was 9.1 % at 5th year and 26.5 % at 10th year . Cox proportional analysis showed that HCC development after the termination of IFN therapy occurred when histological staging was advanced ( P < 0.0001 ) and BR was not achieved ( P = 0.009 ) , age was > 60 years ( P = 0.026 ) . The relative risk of HCC development in patients with BR was 0.36 compared with patients without BR . The attainment of BR during IFN therapy is effective in reducing hepatocarcinogenesis for patients with chronic HCV infection Interferon-alpha ( IFN ) monotherapy results in sustained virological clearance in a minority of patients with chronic hepatitis C. The aim of this study was to assess the effect of a reinforced regimen combining ribavirin and high-dose IFN for 48 weeks compared with a nonreinforced regimen combining a st and ard IFN regimen and ribavirin for 24 weeks in nonresponders with chronic hepatitis C. A total of 231 patients with chronic hepatitis C and previous nonresponse to IFN monotherapy were r and omized . The reinforced group ( n = 114 ) received IFN-2b 6 million units ( MU ) thrice weekly ( TIW ) and ribavirin for 48 weeks , and the nonreinforced group ( n = 117 ) received IFN-2b 3 MU TIW and ribavirin for 24 weeks . The main outcome measure was a sustained virological response , defined as negative serum hepatitis C virus (HCV)-RNA 24 weeks following the end of treatment . This endpoint was determined in 98 patients of the reinforced group and 105 patients of the nonreinforced group . At the end of follow-up , a sustained virological response was observed in 29 of the 98 patients ( 29.6 % ) in the reinforced group vs 16 of the 105 patients ( 15.2 % ) in the nonreinforced group ( P = 0.014 ) . In multivariate analysis , factors associated with a sustained virological response were treated with a reinforced regimen [ odds ratio ( OR ) 2.9 ; P = 0.06 ] and genotype 2 or 3 ( OR 8.8 ; P < 0.0002 ) . A total of 160 patients had paired biopsies before and after treatment . Histological activity improvement was observed in 32 of 80 patients ( 40 % ) and fibrosis worsening in 26 of 80 patients ( 33 % ) in the reinforced group vs 13 of 80 ( 16 % ) and 19 of 80 ( 24 % ) in the nonreinforced group ( P = 0.30 and 0.20 , respectively ) . Hence in nonresponders , a high-dose 48-week regimen of IFN and ribavirin combination was more effective than a regimen with interferon at lower dose and ribavirin for 24 weeks only For chronic hepatitis C virus ( HCV ) infection , interferon-alpha ( IFN-alpha ) treatment has recently been established . However , the complete responding rate is not higher than 20 - 25 % . The aim of our study was to assess IFN-alpha retreatment in chronic hepatitis C. In summary , during a second cycle of IFN-alpha , 60 % of the patients responded to the retreatment . Indeed , a sustained complete response , together with long-lasting normal alanine aminotransferase values and negative serum HCV-RNA , was observed in about 40 % of the retreated patients . Future prospect i ve and controlled trials must define the optimal retreatment strategy , as well as the response-predicting factors including HCV genotypes and quantitative HCV-RNA levels BACKGROUND / AIMS The aim of this study was to increase virologic response rates by individualized treatment according to the early virologic response . METHODS Serum HCV-RNA was frequently quantified in patients with chronic hepatitis C ( n=270 ) treated with peginterferon alfa-2a ( 180 microg/week ) and ribavirin ( 1000 - 1200 mg/day ) . After 6 weeks patients were classified as rapid ( RVR ) , slow ( SPR ) , flat ( FPR ) , or null responders ( NUR ) and r and omized within each viral kinetic class to continue therapy either with an individualized or st and ard regimen . Individualized therapy comprised peginterferon monotherapy ( 48 weeks ) or shorter combination therapy ( 24 weeks ) for RVR , triple therapy with histamine ( 1 mg/day ) ( 48 weeks ) or prolonged combination therapy ( 72 weeks ) for SPR , triple therapy for FPR , and high-dose peginterferon ( 360 microg/week ) plus ribavirin for NUR patients . RESULTS Patients were categorized as RVR ( n=171 ) , SPR ( n=65 ) , FPR ( n=10 ) , or NUR ( n=22 ) . Overall end-of-treatment and sustained virologic response rates were 77 and 60 % in the individualized and 77 and 66 % in the st and ard treatment arm , respectively . Histamine in addition to peginterferon and ribavirin and high-dose peginterferon plus ribavirin did not improve virologic response rates in patients with FPR and NUR , respectively . CONCLUSIONS An improvement in virologic efficacy was not achieved with the available individualized treatment options BACKGROUND / AIMS Our aim was to assess whether histological response was improved by continuing interferon-alpha ( IFN ) treatment in patients with chronic hepatitis C ( HCV ) with a biochemical response and no viral clearance after a usual IFN treatment . METHODS Fifty-seven patients with normal alanine aminotransferase ( ALAT ) levels and positive HCV RNA at the end of a 1 year IFN treatment were r and omly assigned to either group 1 ( n = 28 ) where IFN was stopped , or group 2 ( n = 29 ) where IFN was continued for 1 more year with gradual reduction of the dose to keep serum ALAT activity below the upper limit of normal . Liver biopsies were obtained before , and then 6 months after the end of treatment . RESULTS Knodell 's index improved between paired biopsies in group 2 ( 8.2+/-2.4 vs. 5.5+/-2.1 ) , but not in group 1 ( 8+/-2.3 vs. 6.5+/-2 ) . In post-treatment biopsies , the METAVIR activity score was significantly lower in group 2 than in group 1 ( 0.7+/-0.2 vs. 1.1+/-0.3 , P < 0.05 ) . In group 2 , an improvement of the METAVIR fibrosis score was observed ( 1.3+/-0.4 vs. 1.1+/-0.2 ) , whereas fibrosis progressed in group 1 ( 1.3+/-0.4 vs. 1.6+/-0.4 ) . CONCLUSIONS Maintenance therapy by the minimal dose of IFN able to maintain biochemical response prevents histological progression in the sub-group of patients without virological response R and omized clinical trials ( RCTs ) provide the most reliable therapeutic information available . Unfortunately , there are no systemic listing of RCTs . We compared a MEDLARS search of 3686 biomedical journals for RCTs with a manual search of the medical literature for the period 1966 - 1982 . For the former search we used subject headings ( 1 ) liver disease or ( 2 ) biliary tract disease and subheadings ( 1 ) drug therapy , ( 2 ) surgery , ( 3 ) radiotherapy , or ( 4 ) therapy , and check tags ( 1 ) comparative study or ( 2 ) clinical research . For the manual search , the contents of 34 arbitrarily selected , gastroenterologic , hepatologic , surgical , or general journals were perused . The MEDLARS search identified 160 RCTs and 29 others were found in the references of the 160 . One hundred fifty-four RCTs were identified by both methods . The manual search identified 208 RCTs and an additional 34 were found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found in the references of the 208 . The MEDLARS search identified only 107 of 208 RCTs found manually in the 36 journals , an efficiency rate of 51 % . We estimate that 330 hepatobiliary RCTs had been published during this 17-year period . Sixty percent of the RCTs found by MEDLARS used the key word " r and omized , " " double blind , " or " controlled " in the title , compared to 36 % in those found by the manual search . In order to retrieve RCTs , it is essential that editors require that RCTs be identified in their titles or key words by specific terms such as " controlled , " " r and omized , " and " double blind , " that papers be so catalogued and indexed , and that search ers be instructed in appropriate search strategies The coadministration of ribavirin with recombinant interferon alfa-2b ( rIFN-alpha 2b ) compared with rIFN-alpha 2b alone markedly enhanced sustained virologic response rates in relapsed and treatment-naive chronic hepatitis C patients . The potential for ribavirin to likewise exacerbate the adverse events associated with the alpha interferons is review ed . The overall safety and tolerability of combination rIFN-alpha 2b/ribavirin therapy was evaluated in 2,089 patients treated in phase III clinical studies conducted in the United States and internationally . Serious adverse events were also evaluated on an interim basis in > 25,000 patients --a majority of whom were treated with combination therapy ( open label)--treated worldwide in investigator-initiated studies . Patients in the phase III studies received 3 million International Units rIFN-alpha 2b three times per week by subcutaneous injection plus either ribavirin or placebo orally in divided daily doses of 1,000 or 1,200 mg for patients weighing < or = 75 or > 75 kg , respectively . Adverse event frequency and severity and dose modifications were recorded throughout the 24-week ( relapse ) or 48-week ( naive ) treatment period and 24-week follow-up period . Clinical ly significant adverse events included anemia and depression . There was no evidence that the adverse effects of alpha interferon ( e.g. , fatigue , depression , neutropenia ) were exacerbated by ribavirin . Severe adverse events were limited due to strict adherence to dose-modification criteria ; approximately 6 % to 9 % of patients discontinued combination therapy because of an adverse event . Clinical ly serious adverse events , dose reductions and discontinuations , and potential mechanisms of toxicity associated with rIFN-alpha 2b and ribavirin are examined In chronic hepatitis C the rate of relapse afteran end-of-treatment response to interferon may exceed50 % . The usefulness of retreatment of relapsers withinterferon in obtaining a complete sustained response and the role of clinical , virological and immunological features in determining long-term efficacyof retreatment are unclear . We aim ed to assess theefficacy of interferon retreatment in obtaining acomplete sustained response , to evaluate whetherincreasing the dose may enhance responsiveness , and toidentify possible predictors of sustained response . Weenrolled 42 patients with biopsy-proven chronichepatitis C without cirrhosis who had previouslyresponded to a six-month course ofInterferon-α2b ( total dose : group A , 22 patients , 234 MU ; group B , 20 patients , 468 MU ) and thenrelapsed . All , except one , were HCV-RNA negative at the end of first cycle ofinterferon ; most ( 31/42 , 74 % ) were infected by HCV 1b . Subjects were r and omly allocated to receive anothercycle of interferon either at the original dose ( group A1 : 234 MU , 11 patients ; groupB 468 MU , 10 patient ) or twice the original dose ( groupA2 : 468 MU , 11 patients ; group B : 936 MU , 10 patients ) . At the end of the second cycle of interferon,24 subjects ( 57 % ) had normal ALT and were HCV-RNAnegative , and 16 ( 39 % ) had normal ALT , but were HCV-RNApositive . A complete sustained response was obtained ineight patients ( 19 % ) , at a similar rate in all treatment groups . Complete sustainedresponders were different from the other patients interms of age ( 35.9 ± 10.4 vs 44.1 ± 8.8,P = 0.027 ) , rate of infection with non-1b HCV ( 6/8 vs5/34 , P = 0.0005 ) , serum HCV-RNA ( 74,016 vs 321,428median copies/ml , P = 0.037 ) and serum levels of90K/MAC-2 BP ( 5.76 ± 3.01 vs 10.25 ± 5.16units/ml , P = 0.02 ) , an N-glycoprotein implicated incellular defense functions . Multivariate logistic analysis vali date d age and HCV genotype as independent predictorsof CSR . Among noncirrhotic relapsers who received atotal interferon dose ≥234 MU in the first cycle , retreatment usually induced end-of-treatment response . Acomplete sustained response was obtained in only one ofevery five subjects . Increasing the dose of interferonabove that of the first cycle did not enhance the rate of sustained response . In conclusion we might assert that young subjects infected by non-1bHCV and with low levels of HCV-RNA and of 90K/MAC-2 BPare the best c and i date s for retreatment Hepatitis C virus ( HCV ) infection refractory to previous therapy is common . Treatment of patients with refractory disease is difficult and less studied . Pegylated interferon α-2b plus ribavirin is used for treatment of HCV patients naïve to therapy . We conducted a r and omized study for refractory HCV patients using a high- vs. a low-dose pegylated interferon α-2b and ribavirin protocol . Our aim was ( 1 ) to determine the efficacy of pegylated interferon α-2b plus ribavirin to eradicate HCV in previously treated individuals and ( 2 ) to compare a low-dose to a high-dose regimen . One hundred fifty-two patients were initiated in the study , 112 ( 74 % ) were male and 40 ( 26 % ) female . Nineteen percent of patients obtained a sustained viral response ( SVR ) in the high-dose arm . Prior relapsers had the highest SVR rates : 50 % in non-genotype 1 and 34 % in genotype 1 . The odds of achieving a SVR were six times higher in previous relapsers . The rate of SVR in genotype 1 patients who were nonresponders to prior therapy was only 8 % . All patients who achieved a SVR had no detectable virus at week 24 . However , only half of those who had undetectable viral titers at week 24 achieved a SVR . In conclusion , retreatment of patients with refractory hepatitis C infection with interferon α-2b and ribavirin combination therapy is well tolerated and gives modest response rates . The most important factor in predicting response to therapy is the manner of response to previous treatment . The likelihood of response to treatment can be predicted from the viral titers at 24 weeks Chronic active hepatitis due to HCV represents a severe progressive disorder of the liver , At present , Interferon seems to be the most efficacious treatment available , however , only 20 - 25 % of the patients treated achieve complete remission . The efficacy has , therefore , been evaluated of Ribavirin , a nucleoside analogue active both on DNA and RNA viruses , in the treatment of non responders to a previous course of interferon . Twenty patients were r and omly assigned to two groups : A ) received the association R ( 800 mg/day for 2 months)+interferon ( 9 Mu/week for 6 months ) ; B ) received IFN ( 9 Mu/week for 6 months ) . All patients completed the study without important side effects . Four patients in group A presented reduced ALT and loss of viraemia during treatment with Ribavirin . Only one patient in group B had reduced indices of cell lysis and was negative for HCV-RNA during the course of the study . However , viremia and an increase of ALT values were observed in all of these subjects once treatment was interrupted . The results emerging from this study indicate that Ribavirin therapy , at the dose and duration of treatment employed , is not sufficient to change the natural course of events of chronic active hepatitis from HCV To determine whether a higher dosage of interferon ( IFN ) and /or a prolonged time of administration may improve the efficacy of combination therapy , we conducted a 4-arm r and omized trial on patients with chronic hepatitis C relapsing after 1 or more previous treatment courses with IFN monotherapy . Group A ( n = 70 ) received 3 MU IFN alfa-2b 3 times per week plus ribavirin 1,000 mg/d for 12 months ; group B ( n = 70 ) received 5 MU 3 times per week plus ribavirin for 12 months ; group C ( n = 82 ) received 3 MU 3 times per week plus ribavirin for 6 months , and group D ( n = 73 ) received 5 MU 3 times per week plus ribavirin for 6 months . The primary end point was the clearance of viremia at the end of 6-month follow-up : test results for hepatitis C virus (HCV)-RNA were negative in 54 % of group A , 56 % of group B , 40 % of group C , and 49 % of group D patients ( P = NS ) . Among patients with genotype 1 and 4 , the sustained response was significantly higher in groups A and B than in group C ( 45 % , 49 % vs. 22 % , P = .03 ; group D = 33 % , P = NS ) . In patients with genotype 2 and 3 , the sustained virologic response was not affected by the different regimens ( group A = 69 % , group B = 68 % , group C = 62 % , group D = 71 % , P = NS ) . In conclusion , duration of therapy rather than IFN dosage is more important in increasing the sustained virologic rate among HCV-positive patients with genotype 1 and 4 relapsing after IFN monotherapy ; patients with genotypes 2 and 3 can be effectively retreated with a 6-month course of combination therapy , avoiding unnecessary side effects and waste of re sources Background After the discovery of type C hepatitis virus , the studies on this virus are extensively progressing . The treatment of this viral infection is also widely progressing . Among many agents , recombinant interferon alpha therapy is generally accepted as an effective single agent . To evaluate the efficacy of interferon and to observe the changes of serum aminotransferase ( ALT ) , antibody to hepatitis C virus ( anti-HCV ) and HCV ribonucleic acid ( HCV-RNA ) , we treated 10 patients with chronic type C hepatitis for 6 months . Methods Patients were r and omly divided into 2 groups : 5 patients in group A received interferon and the other 5 in group B received no therapy . Interferon was administered at a dose of 3 million units ( MU ) daily for the first month and thrice weekly for the following 5 months , and followed up for 2 years . Results In group A , serum ALT returned to normal in 4 : 3 , starting at the first month and one at the 3rd month of therapy and maintained normal throughout the follow-up period . In contrast , serum ALT level persistently fluctuated in 4 patients in group B. In one patient , serum ALT returned to normal one and a half years later . Regardless of therapy , serum anti-HCV titer remained unchanged in all patients . However , HCV-RNA , using polymerized chain reaction ( PCR ) , became undetetable in all responded patients and in one untreated patient whose serum ALT returned to normal spontaneously . Conclusion This study suggested that interferon alpha therapy in patients with chronic type C hepatitis may be clinical ly effective . Our study also indicated that the detection of HCV-RNA by PCR is useful to predict the prognosis of chronic type C hepatitis OBJECTIVES To analyze sources search ed in Cochrane review s , to determine the proportion of trials included in review s that are indexed in major data bases , and to compare the quality of these trials with those from other sources . METHODS All new systematic review s in the Cochrane Library , Issue1 2001 , that were restricted to r and omized controlled trials ( RCTs ) or quasi- RCTs were selected . The sources search ed in the review s were recorded , and the trials included were checked to see whether they were indexed in four major data bases . Trials not indexed were checked to determine how they could be identified . The quality of trials found in major data bases was compared with those found from other sources . RESULTS The range in the number of data bases search ed per review ranged between one and twenty-seven . The proportion of the trials in the four data bases were Cochrane Controlled Trials Register = 78.5 % , MEDLINE = 68.8 % , Embase = 65.0 % , and Science/Social Sciences Citation Index = 60.7 % . Search ing another twenty-six data bases after Cochrane Controlled Trials Register ( CCTR ) , MEDLINE , and Embase only found 2.4 % additional trials . There was no significant difference between trials found in the CCTR , MEDLINE , and Embase compared with other trials , with respect to adequate allocation concealment or sample size . CONCLUSIONS There was a large variation between review s in the exhaustiveness of the literature search es . CCTR was the single best source of RCTs . Additional data base search ing retrieved only a small percentage of extra trials . Contacting authors and manufacturers to find unpublished trials appeared to be a more effective method of obtaining the additional better quality trials Aim : To compare the efficacy of high‐dose induction with st and ard dose interferon therapy for the treatment of chronic hepatitis C virus at the Dallas Veterans Affairs Medical Center BACKGROUND Pegylated interferons ( Peg-IFNs ) represent , in association with Ribavirin , the first line of treatment in chronic C viral hepatitis . The AIM of our paper was to compare the efficacy of Peg-IFN alpha 2a ( Pegasys ) and Peg-IFN alpha 2b ( PegIntron ) in a group of patients from the Department of Gastroenterology in Timisoara . MATERIAL AND METHOD 116 patients with chronic C viral hepatitis were treated . The patients were r and omized in chronological order ( 1:1 ) , so that 58 patients were treated with Peg-IFN alpha 2a 180 microg/kg/week + Ribavirin ( group 1 ) and 58 were treated with Peg-IFN alpha 2b 1.5 microg/kg/week + Ribavirin ( group 2 ) . Ribavirin was administered in the recommended doses , according to weight . The mean age was : group 1 -- 49.3 years , group 2 -- 50.9 years ( p=0.37 ) . Group 1 consisted of 37 women and 21 men and group 2 of 44 women 14 men ( p=0.22 ) . In group 1 , 48 patients were naïve ( N1 ) , 7 were relapsers after previous treatment ( RL1 ) and 3 non-responders to previous treatment ( NR1 ) . In group 2 , 33 patients were naive ( N2 ) , 18 relapsers ( RL2 ) and 7 non-responders ( NR2 ) . After 12 weeks of treatment we evaluated the early virological response ( EVR ) , defined as a drop in the viral load with 2 logs compared to the baseline viremia . RESULTS The following EVR rates were found : in group 1 ( Pegasys ) - 82.2 % ( 48/58 ) ; in group 2 ( PegIntron ) -- 67.2 % ( 39/58 ) ( p=0.08 ) . There were also no significant statistical differences between the response rates in the subgroups : naïve patients [ 89.6 % vs. 75.2 % , p = 0.61 ] , relapsers [ 57.1 % vs. 66.6 % , p = 0.67 ] and non responders [ 33.3 % vs. 28.6 % , p = 1 ] . CONCLUSION Our head to head comparative study showed that there are no statistically significant differences in the EVR between the patients treated with Peg-IFN alpha 2a and Peg-IFN alpha 2b OBJECTIVES : To evaluate whether in chronic hepatitis C-positive patients who failed to respond to interferon ( IFN ) monotherapy a sustained response obtained with retreatment using the combination therapy of IFN + ribavirin can be safely considered to reflect eradication of the infection . METHODS : Prospect i ve follow-up of a cohort of 97 patients who responded to retreatment with different regimens of IFN + ribavirin after failing to respond to a first IFN monotherapy course . The patients were followed throughout 7 yr of follow-up with determinations of HCV viremia every 6 months . RESULTS : At the end of the follow-up , 11 patients ( 11.3 % ) showed a viremic reappearance . HCV late relapse rates were 0 % , 13 % , 20 % , and 12 % in patients retreated , respectively , with 3 MU IFN + ribavirin for 12 months ( Group 1 ) , 5 MU IFN + ribavirin for 12 months ( Group 2 ) , 3 MU IFN + ribavirin for 6 months ( Group 3 ) , and 5 MU IFN + ribavirin for 6 months ( Group 4 ) ( Group 2 vs Group 3 , p = 0.005).The virologic relapses occurred within 2 yr from therapy withdrawal . Among patients with genotype 1 and 4 , the long-term response was significantly higher in Group 2 than in Group 3 ( 15 % vs 3 % , p = 0.03 ) . In patients with genotype 2 and 3 , the long-term virological response was not affected by the different regimens . CONCLUSIONS : Nonresponders to IFN monotherapy who achieve a sustained virologic response after retreatment with IFN + ribavirin st and a discrete risk of HCV reactivation within 2 yr after therapy BACKGROUND Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy . We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 912 patients with chronic hepatitis C to receive st and ard-dose interferon alfa-2b alone or in combination with ribavirin ( 1000 or 1200 mg orally per day , depending on body weight ) for 24 or 48 weeks . Efficacy was assessed by measurements of serum hepatitis C virus ( HCV ) RNA and serum aminotransferases and by liver biopsy . RESULTS The rate of sustained virologic response ( defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed ) was higher among patients who received combination therapy for either 24 weeks ( 70 of 228 patients , 31 percent ) or 48 weeks ( 87 of 228 patients , 38 percent ) than among patients who received interferon alone for either 24 weeks ( 13 of 231 patients , 6 percent ) or 48 weeks ( 29 of 225 patients , 13 percent ) ( P<0.001 for the comparison of interferon alone with both 24 weeks and 48 weeks of combination treatment ) . Among patients with HCV genotype 1 infection , the best response occurred in those who were treated for 48 weeks with interferon and ribavirin . Histologic improvement was more common in patients who were treated with combination therapy for either 24 weeks ( 57 percent ) or 48 weeks ( 61 percent ) than in those who were treated with interferon alone for either 24 weeks ( 44 percent ) or 48 weeks ( 41 percent ) . The drug doses had to be reduced and treatment discontinued more often in patients who were treated with combination therapy . CONCLUSIONS In patients with chronic hepatitis C , initial therapy with interferon and ribavirin was more effective than treatment with interferon alone Purpose . Although interferon ( IFN ) is commonly used for the treatment of chronic hepatitis C virus ( HCV ) infection , eradication of the virus occurs in only a small proportion of patients with genotype 1b and a high virus titer . Modified IFN therapies have been tried , with only limited benefit . Recently , the administration of IFN-beta twice per day has been reported to be more effective than the usual once-daily administration regimen . The aim of this study was to evaluate whether twice-daily IFN results in a sustained response in patients with chronic HCV infection with genotype 1b and a high virus titer . Methods . Twenty patients with genotype 1b and high HCV RNA level ( more than 1 MEq/ml by branched DNA probe assay ) were r and omly assigned to receive either twice-daily 3 MU of IFN beta ( group A ) or once-daily 6 MU of IFN-beta ( group B ) for 4 weeks . All patients received a further daily dose of 6 MU IFN-beta for 12 weeks , followed by IFN-alfa three times a week for 16 weeks . Results . Although a rapid fall in HCV RNA levels was noted in group A , a sustained response was observed in only one of nine patients in this group , and none of group B. Adverse effects of IFN were more frequent and pronounced in group A than in group B. Conclusions . We conclude that further modification , which combines the early strong anti-viral effects of the twice-daily regimen with long-term sustained response , is necessary for effective therapy of HCV patients with genotype 1b and high HCV RNA levels Background A substantial proportion of patients with chronic hepatitis C virus ( HCV ) cirrhosis fail to eradicate infection and develop liver-related complications . Despite evidence that interferon-&agr ; has an antifibrotic effect , clinical trials have demonstrated that low-dose maintenance interferon does not improve outcomes in patients with compensated HCV cirrhosis following a lead-in phase of interferon . In a pilot study , we have investigated the efficacy of an escalating dose of pegylated interferon & agr;-2a ( PEG-IFN2a ) as compared with st and ard clinical care in patients with more advanced HCV Child ’s A or B cirrhosis without a lead-in phase . Methods In a prospect i ve study , 40 patients were r and omized to receive either st and ard clinical care ( no further antiviral therapy ) or 48 weeks of treatment with PEG-IFN2a starting at 90 mcg and escalating to 180 mcg weekly if tolerated . Patients were thereafter followed for a mean duration of 41 months . The primary outcome variables were liver-related death , all-cause mortality and sustained virological response . The secondary outcomes were ‘ liver-related events ’ and health-related quality of life . Results Both groups were well matched , with treatment well tolerated . The incidences of all-cause mortality ( P=0.024 ) and nononcological liver morbidity ( P=0.04 ) were significantly higher in the control arm after a mean of 47 months of follow-up . Conclusion A 48-week escalating dose of PEG-IFN2a is associated with a significant reduction in all-cause mortality and nononcological liver-related morbidity in this trial . Further investigation of PEG-IFN2a is warranted for patients with advanced HCV-related cirrhosis for whom there is no other treatment and where transplantation is associated with rapid progression to cirrhosis BACKGROUND A sustained virological response ( SVR ) rate of 41 % has been achieved with interferon alfa-2b plus ribavirin therapy of chronic hepatitis C. In this r and omised trial , peginterferon alfa-2b plus ribavirin was compared with interferon alfa-2b plus ribavirin . METHODS 1530 patients with chronic hepatitis C were assigned interferon alfa-2b ( 3 MU subcutaneously three times per week ) plus ribavirin 1000 - 1200 mg/day orally , peginterferon alfa-2b 1.5 microg/kg each week plus 800 mg/day ribavirin , or peginterferon alfa-2b 1.5 microg/kg per week for 4 weeks then 0.5 microg/kg per week plus ribavirin 1000 - 1200 mg/day for 48 weeks . The primary endpoint was the SVR rate ( undetectable hepatitis C virus [ HCV ] RNA in serum at 24-week follow-up ) . Analyses were based on patients who received at least one dose of study medication . FINDINGS The SVR rate was significantly higher ( p=0.01 for both comparisons ) in the higher-dose peginterferon group ( 274/511 [ 54 % ] ) than in the lower-dose peginterferon ( 244/514 [ 47 % ] ) or interferon ( 235/505 [ 47 % ] ) groups . Among patients with HCV genotype 1 infection , the corresponding SVR rates were 42 % ( 145/348 ) , 34 % ( 118/349 ) , and 33 % ( 114/343 ) . The rate for patients with genotype 2 and 3 infections was about 80 % for all treatment groups . Secondary analyses identified bodyweight as an important predictor of SVR , prompting comparison of the interferon regimens after adjusting ribavirin for bodyweight ( mg/kg ) . Side-effect profiles were similar between the treatment groups . INTERPRETATION In patients with chronic hepatitis C , the most effective therapy is the combination of peginterferon alfa-2b 1.5 microg/kg per week plus ribavirin . The benefit is mostly achieved in patients with HCV genotype 1 infections BACKGROUND & AIMS : At least half of patients with chronic hepatitis C virus ( HCV ) fail to respond to interferon or interferon/ribavirin therapy . Histological improvement is observed in some nonresponders . We conducted a r and omized , controlled trial to determine if maintenance interferon therapy could prevent histological progression in this subset of nonresponders . METHODS Fifty-three patients with chronic HCV were enrolled . All were HCV-RNA positive after 6 months of treatment with interferon alfa-2b but had a histological response . Twenty-seven of the patients were r and omly assigned to continue interferon ( 3 MU 3 times weekly ) for 24 months ; 26 patients discontinued treatment and were observed prospect ively . Alanine aminotransferase ( ALT ) level and HCV-RNA titer were monitored , and liver biopsy was repeated every 12 months . RESULTS Before interferon therapy , the 2 groups were well matched for all demographic factors , serum ALT ( 94.0 + /- 15.6 ) , log HCV-RNA titer ( 5 . 85 + /- 0.15 copies/mL ) , histology score ( 9.5 + /- 0.2 ) , and percentage with cirrhosis ( 25 % ) . After 6 months of treatment , significant reductions ( P < 0.05 ) in serum ALT level ( 62.6 + /- 9.6 ) , log HCV-RNA titer ( 4.79 + /- 0.13 copies/mL ) , and hepatic inflammation ( 4.0 + /- 0.2 ) were observed . These improvements were maintained in the patients r and omized to continue interferon . Stopping treatment was associated with an increase in serum ALT , log HCV-RNA , and hepatic inflammation back to baseline . After 30 months of treatment , mean fibrosis score declined from 2.5 to 1.7 and 80 % of patients had histological improvement ( P < 0.03 ) . Discontinuation of interferon was associated with an increase in mean fibrosis score from 2.2 to 2.4 and worsening of hepatic histology in 30 % of patients ( P < 0.01 ) . CONCLUSIONS These data support the hypothesis that maintenance interferon may prevent histological progression of chronic HCV in patients who remain viremic BACKGROUND Interferon alfa is the only effective treatment for patients with chronic hepatitis C. Forty percent of patients have an initial response to this therapy , but most subsequently relapse . We compared the effect of interferon alone with that of interferon plus oral ribavirin for relapses of chronic hepatitis C. METHODS We studied 345 patients with chronic hepatitis C who relapsed after interferon treatment . A total of 173 patients were r and omly assigned to receive st and ard-dose recombinant interferon alfa-2b concurrently with ribavirin ( 1000 to 1200 mg orally per day , depending on body weight ) for six months , and 172 patients were assigned to receive interferon and placebo . RESULTS At the completion of treatment , serum levels of hepatitis C virus ( HCV ) RNA were undetectable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone ( 82 percent vs. 47 percent , P<0.001 ) . Serum HCV RNA levels remained undetectable 24 weeks after the end of treatment in 84 patients ( 49 percent ) in the combination-therapy group , but in only 8 patients ( 5 percent ) in the interferon group ( P<0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations and histologic improvement were highly correlated with virologic response . Base-line serum HCV RNA levels of 2 x 10(6 ) copies per milliliter or less were associated with higher rates of response in both treatment groups . Viral genotypes other than type 1 were associated with sustained responses only in the combination-therapy group . Combined therapy caused a predictable fall in hemoglobin concentrations but otherwise had a safety profile similar to that of interferon alone . CONCLUSIONS In patients with chronic hepatitis C who relapse after treatment with interferon , therapy with interferon and oral ribavirin results in higher rates of sustained virologic , biochemical , and histologic response than treatment with interferon alone BACKGROUND / AIMS Chronic hepatitis C ( HCV ) patients who have failed previous treatment have low sustained viral response ( SVR ) rates with repeat treatment . We evaluated whether interferon ( IFN ) induction during retreatment improves response rates . METHODS Two r and omized , controlled trials were conducted in chronic HCV patients who failed IFN . In Study 1 , patients received IFN 3 MU daily plus ribavirin ( RBV ) 1000 mg/day for 4 weeks , followed by IFN 3 MU TIW plus RBV 1000 mg/day for 44 weeks ( induction ; n=232 ) , or IFN 3 MU TIW plus RBV 1000 mg/day for 48 weeks ( non-induction ; n=237 ) . In Study 2 , patients received IFN 5 MU B.I.D. plus RBV 1000 - 1200 mg/day for 2 weeks , followed by pegylated IFN ( PEG-IFN ) 75 - 150 mug weekly plus RBV 1000 - 1200 mg/day for 46 weeks ( induction ; n=201 ) , or PEG-IFN 75 - 150 mug weekly plus RBV 1000 - 1200 mg/day for 48 weeks ( non-induction ; n=206 ) . The primary end point for both trials was SVR . RESULTS Induction did not increase SVR compared with non-induction , but did increase the on-treatment response among genotype non-1 patients in Study 2 . By intention-to-treat ( ITT ) analysis , SVR in Study 1 was 13 % for induction vs. 9 % for non-induction ( P = NS ) . In Study 2 ( ITT ) , SVR was 20 % for induction vs. 24 % for non-induction ( P = NS ) . However , by non-ITT analysis of Study 2 , genotype non-1-previous non-responders showed significantly higher response rates with induction than non-induction . CONCLUSION For chronic HCV patients who have failed IFN , induction with retreatment does not improve SVR , but may be beneficial for patients with genotype non-1 HCV Nine patients with chronic hepatitis C virus ( HCV ) infection and no complete response to the first treatment with natural interferon (IFN)-alpha , were prescribed a second treatment with IFN . Five patients ( Group A ) with unsustained levels serum alanine aminotransferase ( ALT ) after the first treatment were administrated the same species of IFN but in a higher dose . The remaining four patients ( Group B ) , with no normalization of ALT throughout the observation period of the first treatment , were administrated IFN-beta . HCV RNA was eliminated in three patients of group A and in two of group B patients during 6 months follow up and ALT reverted to normal levels . These results suggest that retreatment with a higher dose of the same species of IFN-alpha can be effective in case of a relapse and that IFN-beta can be effective for those not responding to IFN-alpha Patients with biopsy-proven chronic hepatitis C , who failed to respond to a previous course of either recombinant ( rIFN-alpha ) or lymphoblastoid ( Ly IFN-alpha ) interferon-alpha , were r and omized to receive either leucocyte ( Le ) IFN-alpha ( patients ) or a second course of the same IFN-alpha ( controls ) , to compare the efficacy and safety of these treatment schedules . All patients received the same dose of IFN-alpha as was used during their previous treatment ( 3 million units ( MU ) or 6 MU three times weekly ) for 6 months . Patients with a normal alanine aminotransferase ( ALT ) value at month 6 were treated for a further 6 months . All patients were followed-up for 12 months after treatment . A total of 69 patients were enrolled , 44 in the Le IFN-alpha group and 25 in the control group . At the end of the treatment period , 13 of the 44 patients ( 29.5 % ) in the Le IFN-alpha group had a biochemical response ( normal ALT ) and six of 44 ( 13.6 % ) patients had undetectable serum hepatitis C virus ( HCV ) RNA . At the end of the follow-up period , 10 patients ( 22.7 % ) had normal ALT values and serum HCV RNA was undetectable in three ( 6.8 % ) . None of the patients in the control group showed normal ALT values at any time . Genotype 1b tended to be more frequent among non-responders ( 61 vs 45 % ) : basal gamma-glutamyl transpeptidase ( gamma-GT ) values were lower in responders than in non-responders ( 33.3 + /- 11.70 Ul-1 vs 58.4 + /- 33.04 ; P = 0.01 ) . Le IFN-alpha was well tolerated by all patients . These results support the use of Le IFN-alpha in patients with chronic hepatitis C who are non-responders to a previous treatment with recombinant or lymphoblastoid IFN-alpha AIM To evaluate the daily high-dose induction therapy with interferon-alpha2b ( IFN-alpha2b ) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse , based on the assumption that the viral burden would decline faster , thus increasing the likelihood of higher response rates in this difficult-to-treat patient group . METHODS Seventy patients were enrolled in this study . Treatment was started with 10 MU IFN-alpha2b daily for 3 wk , followed by IFN-alpha2b 5 MU/TIW in combination with ribavirin ( 1 000 - 1 200 mg/d ) for 21 wk . In case of a negative HCV RNA PCR , treatment was continued until wk 48 ( IFN-alpha2b 3 MU/TIW+1 000 - 1 200 mg ribavirin/daily ) . RESULTS The dose of IFN-alpha2b or ribavirin was reduced in 16 % of patients because of hematologic side effects , and treatment was discontinued in 7 % of patients . An early viral response ( EVR ) was achieved in 60 % of patients . Fifty percent of all patients achieved an end-of-treatment response ( EOT ) and 40 % obtained a sustained viral response ( SVR ) . Patients with no response had a significantly lower response rate than those with a former relapse ( SVR 30 % vs 53 % ; P = 0.049 ) . Furthermore , lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype ( SVR 28 % vs 74 % ; P = 0.001 ) . As a significant predictive factor for a sustained response , a rapid initial decline of HCV RNA could be identified . No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus . CONCLUSION Daily high-dose induction therapy with interferon-alpha2b is well tolerated and effective for the treatment of non-responders and relapsers , when interferon monotherapy fails . A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response BACKGROUND More than 70 % of patients with chronic hepatitis C are resistant to interferon therapy . Ribavirin , in association with interferon , has been demonstrated as effective , at a dose of 800 - 1200 mg/day , but the efficacy of a lower dose has not been established . METHODS We assessed the effectiveness of the combination of 600 mg/day of ribavirin plus 3 MU of interferon over a period of 6 months , in a group of patients previously resistant to interferon . Sixty-two patients with chronic hepatitis C with serum and hepatic HCV RNA relapsers or non-responders to interferon , were r and omly divided into two groups : group A received 3 MU of interferon alpha-2b , three times a week for 6 months ; group B was given the same dose plus 600 mg per day of ribavirin for 6 months . Two patients from each group dropped from therapy . One patient from group A and two from group B withdrew from treatment because of adverse effects . RESULTS Mean alanine aminotransferase levels were similar in both groups throughout the study . A sustained response was observed in 7 % and 7.4 % of groups A and B with short-term response in 39 % and 59 % , and no response in 54 % and 34 % from both groups respectively ( non-significant ) . At 12 months , 4 and 7 patients from groups A and B respectively , cleared serum HCV RNA however , only one sustained responder from each group cleared HCV RNA from peripheral blood mononuclear cells . At 18 months , 3 patients remained serum HCV RNA negative . Adverse effects were similar . Only haemoglobin values were lower in group B in the first month of therapy ( p<0.05 ) . CONCLUSION In conclusion , the combination of 3 MU of interferon plus 600 mg of ribavirin is not effective in chronic hepatitis C resistant to interferon The long-term outcome of patients with hepatitis C virus ( HCV ) infection is difficult to determine for several reasons . First , the initial bout of acute HCV infection is rarely recognized because of the paucity or complete absence of symptoms ( 1 ) . Second , even persons who have established chronic hepatitis are rarely symptomatic . Third , end-stage liver disease , when it occurs , can often take more than three decades to develop ( 2 , 3 ) . To address these issues , investigators have studied HCV infection in setting s that allow accurate determination of onset , such as transfusion-transmitted HCV ( 4 - 8 ) or outbreaks of HCV infection that can be attributed to receipt of contaminated immunoglobulin ( 9 , 10 ) . Several studies ( 9 - 12 ) have shown that major sequelae of chronic HCV infection , decompensated cirrhosis and hepatocellular carcinoma , are relatively uncommon . In contrast , clinical observations in tertiary care and liver transplantation centers suggest that chronic HCV infection is highly likely to have serious or fatal outcomes ( 2 , 3 , 13 , 14 ) . Some research ers believe that prospect i ve studies have been too short to accurately establish outcomes or , in the case of transfusion-related studies , have been limited by premature deaths due to the underlying illness . These concerns could be addressed by study ing young , healthy persons with laboratory-confirmed HCV infection for more extended periods . Through access to frozen serum specimens obtained during the late 1940s and early 1950s from more than 9000 healthy young persons , we were able to implement a retrospective cohort study spanning 45 years to determine liver-related morbidity and mortality in HCV-positive and HCV-negative persons . Methods The Repository Between 1948 and 1955 , epidemiologic and clinical studies were conducted at Fort Francis E. Warren Air Force Base , Wyoming , to investigate the problem of group A streptococcal infection and acute rheumatic fever among military recruits ( 15 , 16 ) . At the conclusion of the study , remaining serum specimens that had been collected from recruits were frozen in rubber-capped glass vials at 20 C. The specimens and the study records were archived by the original investigators . After the subsequent discovery of HCV ( 17 ) and the development of sensitive serologic assays , it became apparent that this unique collection of serum sample s could be a valuable tool for determining the long-term outcome of HCV-positive persons . The serum sample s had been stored frozen and unthawed for at least two decades . When we examined the collection in preparation for this study , we found that vials had been broken and specimens lost for only 0.5 % of the 9451 identified persons . The previously frozen sample s were separated into 1-mL aliquots and were refrozen at 20 C. One aliquot was used for all subsequent tests , and a computerized data base was generated . Serologic Assays Initial anti-HCV assays were performed in the Division of Pediatric Infectious Disease at the University of Minnesota , Minneapolis , Minnesota . Sample s from 9427 persons were assayed in duplicate for antibodies to HCV by third-generation enzyme-linked immunoassay ( EIA 3.0 ) ( Ortho Diagnostics , Raritan , New Jersey ) ( 18 ) . Repeatedly reactive sample s were analyzed by using supplemental recombinant immunoblot assay ( RIBA 3.0 , Ortho Diagnostics ) ; these tests were performed by the manufacturer . Sample s were then tested for HCV RNA by polymerase chain reaction ( 19 ) and by genotyping in the hepatitis research laboratory of the Veterans Affairs Medical Center in Washington , D.C. ( 20 ) . Persons were classified as having HCV infection if their serum sample s demonstrated antibodies to HCV on both EIA 3.0 and RIBA 3.0 . If an EIA-positive result yielded an indeterminate or negative result on RIBA 3.0 , the EIA 3.0 result was considered false-positive ( 21 ) . Serum aminotransferase levels were not measured because activity was probably lost through prolonged storage and because freeze-thaw cycles may have occurred after the original phlebotomy ( 22 ) . Construction of the Study Cohort The criteria for selection of recruits , the periods of observation , and the objectives of the original studies were defined in the original published reports ( 15 , 16 ) . During these studies , only names and military service numbers were recorded . We used this information to obtain additional data , such as Social Security numbers and demographic variables ( including age , ethnicity , and sex ) , from records of the Department of Defense , the National Archives and Records Administration , and the Department of Veterans Affairs . Our analysis was restricted to persons with identifiable Social Security numbers because this information was essential for documenting data on morbidity and mortality . Death certificate information was obtained from the Department of Veterans Affairs and through the National Death Index . Outcomes Morbidity Morbidity diagnoses were obtained from the Department of Veterans Affairs and the Health Care Financing Administration ( HCFA ) . Veterans Affairs data came from Patient Treatment Files , which code patients ' diagnoses at discharge from Veterans Affairs medical centers , and from documentation of disabilities in Compensation and Pension files . The HCFA data came from three files : the Medicare Provider Analysis and Review file , which includes information on diagnoses and procedures for each hospital discharge in the United States ; the Health Information Skeletonized Eligibility Write-off file , which records date s of birth and death that are abstract ed from Social Security records ; and the St and ard Analytical File , which provides data on out patients . Mortality We collected data on all-cause and cause-specific mortality from death certificates in Veterans Affairs cl aims files . The Department of Veterans Affairs maintains a computer file of beneficiaries , including recipients of veterans ' death benefits , and also records deaths that occur during hospitalizations in Veterans Affairs medical centers . Investigation of the extent of reporting has shown that the file is almost complete ( 23 ) . In some instances , we obtained evidence of death from HCFA files , which are derived from Social Security records . The National Death Index Plus service of the National Center for Health Statistics provided additional coded , cause-specific death certificate information from national mortality data . A qualified nosologist coded the underlying causes of death according to the rules that existed at the time of death and recoded them by using the International Classification of Diseases , Ninth Revision , Clinical Modification . Some death certificates and Veterans Affairs cl aims may be incomplete or inaccurate , but the frequency of these events should not differ between the HCV-positive and HCV-negative groups . Statistical Analysis Relative risks and CIs ( Cornfield and exact ) ( 24 ) and results of chi-square tests and the Fisher exact test were calculated by using Epi-Info , version 6.04 ( Centers for Disease Control and Prevention , Atlanta , Georgia ) ( 25 ) . A Kaplan-Meier survival analysis curve ( 26 ) was calculated by using SAS , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) ( 27 ) . A P value less than 0.05 was considered statistically significant . Results Completeness of Identifier and Demographic Data Of 9427 persons , 8568 ( 91 % ) were included in our analysis because they had a Social Security number with which we could obtain information on morbidity and mortality . Most participants were white men who were younger than 25 years of age at the original phlebotomy . Of 6805 persons whose sex was known , 6742 ( 99 % ) were men . Among 6611 persons whose ethnicity was known , 89.3 % were white , 10.3 % were African American , and 0.4 % were Asian . The mean age of surviving cohort members as of 31 December 1996 was 64.8 years , and 95 % were between 60 and 69 years of age . Serologic Data Among the 8568 persons tested , 34 ( 0.4 % ) were repeatedly positive for anti-HCV . Seventeen of these 34 participants ( 50 % ) had positive results on RIBA 3.0 , 9 had indeterminate results , and 8 had negative results . Therefore , the prevalence of RIBA-confirmed anti-HCV reactivity was 0.2 % ( 17 of 8568 ) . At original phlebotomy , the mean age of the HCV-positive group was 21.5 years ( range , 19 to 28 years ; median , 20.5 years ) and the mean age of the HCV-negative group was 20.7 years ( range , 18 to 46 years ; median , 20.0 years ) . A significant difference was seen between the number of African-American persons with confirmed HCV infection ( 12 of 684 [ 1.8 % ] ) and the number of white persons with confirmed HCV infection ( 4 of 5902 [ 0.07 % ] ) ( relative risk , 25.9 [ CI , 8.4 to 80.0 ] ) . Polymerase chain reaction detected HCV RNA in 11 ( 65 % ) of the 17 persons who had positive results on EIA 3.0 and RIBA 3.0 but in no persons who had positive results on EIA 3.0 and indeterminate or negative results on RIBA 3.0 . Ten of the 11 persons who were positive for HCV RNA were classified as having genotype 1b . One person could not be classified . Morbidity Eight HCV-positive participants ( 47 % ) and 3566 HCV-negative participants ( 42 % ) had had at least one hospitalization , outpatient visit , or disease-related compensation award ( relative risk , 1.24 [ CI , 0.5 to 3.2 ] ) . One HCV-positive person had a liver-related diagnosis and was recorded as having chronic liver disease and cirrhosis ( Table 1 ) . Most of the 115 persons who were originally negative for HCV and had liver-related diagnoses were recorded as having chronic liver disease and cirrhosis . No HCV-positive persons had received a diagnosis of liver cancer or had been treated for liver cancer . One HCV-negative person had received outpatient treatment for liver cancer that was described on one occasion as primary and on another as not specified as primary or secondary . Table 1 . Liver-Related Hospitalizations , Outpatient Visits , and Compensation Awards among Persons with ( n=17 ) and Those without ( n=8551 ) Hepatitis C Virus Infection Mortality Through Nine patients with chronic hepatitis C who responded with normal or near-normal serum alanine aminotransferase ( s-ALT ) levels during an initial interferon alpha-2b treatment course , but who had subsequent relapses with elevated s-ALT levels after treatment cessation , were retreated once ( 3 patients ) or twice ( 6 patients ) . The liver histological findings before the first and after the last treatment course were compared . The mean follow-up time between the initial and the follow-up assessment was 44 months ( range 34 - 53 ) . The histological findings were classified as chronic persistent hepatitis ( CPH ) , chronic active hepatitis ( CAH ) or cirrhosis ( Ci ) by using a numerical scoring system assessing each portal zone separately . In the initial biopsy , 2 patients were classified as having CPH and 7 as having CAH , 2 of whom with signs of cirrhosis . According to the conventional classification , 4/9 ( 44 % ) patients improved after treatment , 3/9 ( 33 % ) remained unchanged , and 2/9 ( 22 % ) deteriorated . The mean histological scores for the necro-inflammatory parameters : portal inflammation , piecemeal necrosis , spotty necrosis and fibrosis improved , but the changes did not reach statistical significance . We conclude that repeated interferon alpha-2b treatment courses are probably beneficial in patients with chronic hepatitis C who show a non-sustained response to interferon , since studies on the natural course of chronic hepatitis C have indicated a progressive deterioration of the histological picture in many untreated patients , most marked among those with CAH The hepatocarcinoma ( HCC ) represents one of the major causes of morbidity and mortality in course of chronic HCV correlated hepatopathy . Up to today there are no reliable therapies which can delay or avoid the arising of HCC , nonetheless various Authors have noticed a decrease of such incidence in the subjects treated with interferon ( IFN ) . Such encouraging results have not yet found univocal confirmation in course of compensated cirrhosis ( Child-Pugh A ) . In our experience a cohort of 122 patients prospect ively followed was analysed retrospectively to asses the effect of IFN therapy ( mean follow-up 96 + /- 18.3 months ) . We conducted a r and omized study in compensated cirrhosis with abnormal ALT and HCV-RNA positive serum ( post-transfusional infection ) . Fifty-nine patients ( mean age 55.3 + /- 7 ) received IFN ( 3 MU three times a week for 12 months ) ( 8 stopped therapy for side effects ) , 71 did not receive IFN ( mean age : 56.8 + /- 8) . Baseline characteristics were similar . IFN therapy does not reduce the risk of HCC in compensated cirrhosis . In IFN treated patients it has been noted an improvement in relation with worsening and death/OLT . Moreover , in the non responder group , the number of negative events has been higher than in the sustained responder group and in subjects with relapse . On the contrary , no particular differences have been noticed in relation with the arising of HCC . It can be hypotized that the therapy with IFN does not reduce the risk of HCC in compensated cirrhosis . Such condition represents by itself a risk factor . It can be concluded that the therapy with IFN can be effective in reducing the possibility of clinical -laboratoristic worsening . However , even in case of substained response , the follow-up for the arising of HCC must always be done BACKGROUND & AIMS SCH 503034 is a novel and potent oral hepatitis C virus ( HCV ) protease inhibitor . In this phase Ib study , we assessed safety parameters and virologic response of combination of SCH 503034 plus pegylated ( PEG ) interferon ( IFN ) alpha-2b in patients with HCV genotype 1 infections who were previously nonresponders to PEG-IFN-alpha-2b + /- ribavirin therapy . METHODS This was a multicenter , open-label , 2-dose level , 3-way crossover , r and omized ( to crossover sequence ) study carried out in 3 medical centers in Europe . Adult patients received SCH 503034 200 mg ( n = 14 ) or 400 mg ( n = 12 ) 3 times daily orally and PEG-IFN-alpha-2b 1.5 microg/kg subcutaneously once each week . Patients received SCH 503034 as monotherapy for 1 week , PEG-IFN-alpha-2b as monotherapy for 2 weeks , and combination therapy for 2 weeks with washout periods between each treatment period . RESULTS Combination therapy with SCH 503034 and PEG-IFN-alpha-2b was well tolerated , with no clinical ly significant changes in safety parameters . Mean maximum log(10 ) changes in HCV RNA were -2.45 + /- 0.22 and -2.88 + /- 0.22 for PEG-IFN-alpha-2b plus 200 mg and 400 mg SCH 503034 , respectively , compared with -1.08 + /- 0.22 and -1.61 + /- 0.21 for SCH 503034 200 mg and 400 mg , respectively , and -1.08 + /- 0.22 and -1.26 + /- 0.20 for PEG-IFN-alpha-2b alone in the 200 mg and 400 mg SCH 503034 groups , respectively . CONCLUSIONS SCH 503034 plus PEG-IFN-alpha-2b was well tolerated in patients with HCV genotype 1 nonresponders to PEG-IFN-alpha-2b + /- ribavirin . These preliminary results of antiviral activity of the combination suggest a potential new therapeutic option for this hard-to-treat , nonresponder patient population A r and omized trial was conducted to assess the efficacy of daily ( QD ) or thrice weekly ( TIW ) administration of interferon-alpha ( IFN ) in high doses in combination with ribavirin ( 1.0 - 1.2 g/day ) in patients with chronic hepatitis C ( CHC ) who were nonresponders to previous IFN monotherapy . Interferon was administered as 10 MU IFN ( QD or TIW ) for 4 weeks , followed by 5 MU IFN ( QD or TIW ) for 20 weeks , and then by 3 MU IFN ( QD or TIW ) for 24 weeks . Sustained virological response ( SVR ) was evaluated in 142 patients who received at least one dose of medication . One-fourth of the patients achieved SVR , 26 % of those treated with IFN QD and 25 % of those treated with IFN TIW ( P = 0.85 ) . For genotype 1 patients , SVR rates were 32.4 and 15.8 % for IFN QD and IFN TIW , respectively , whereas for genotype non-1 patients the corresponding SVR rates were 20.6 and 36.4 % , respectively ( test of homogeneity : P = 0.031 ) . This finding was further confirmed by multivariate logistic regression analysis where a statistically significant interaction ( P = 0.012 ) was found between treatment and HCV genotype indicating that the IFN QD regimen was superior to IFN TIW among genotype 1 patients whereas , among genotype non-1 patients , the two treatments were similar ( odds ratio of SVR in IFN QD vs IFN TIW : 3.33 among genotype 1 patients , 95 % CI : 1.00 - 11.14 ) . In conclusion , re-treatment of patients not responding to previous IFN monotherapy with a combination of high daily dose of IFN with ribavirin may be beneficial for genotype 1 infected patients Hepatocellular carcinoma , a major cause of death in patients with cirrhosis , is one of the most prevalent malignant tumors worldwide , and its incidence is increasing [ 1 - 5 ] . After isolation of hepatitis C virus ( HCV ) , most patients with chronic hepatitis and those with cirrhosis of unknown origin were found to be positive for anti-HCV [ 6 - 8 ] . Evidence suggests that HCV-related chronic liver disease plays a role in the development of hepatocellular carcinoma [ 9 - 13 ] . A high proportion of patients with hepatocellular carcinoma have anti-HCV , although the prevalence varies geographically . The highest rate of anti-HCV is in southern Europe and Japan , where about 70 % of patients with hepatocellular carcinoma are positive for anti-HCV [ 5 ] . Interferon has been widely used to treat chronic HCV infection . A series of clinical trials showed that some patients who received interferon had sustained normalization of serum aminotransferase levels and elimination of serum HCV RNA [ 14 - 17 ] . Histologic improvement was also seen in patients who received interferon [ 14 , 18 - 20 ] . It is important to determine whether interferon treatment also lowers the incidence of hepatocellular carcinoma in patients with chronic hepatitis C , but the recognized benefits of interferon make a r and omized , controlled trial to address this question unethical . We did a retrospective study to compare the incidence of hepatocellular carcinoma in interferon-treated patients with HCV infection and histologically proven chronic hepatitis or cirrhosis with that in historical controls who did not receive interferon . We also examined the relation between response to interferon therapy and incidence of hepatocellular carcinoma . Methods Patients The interferon group comprised 419 consecutive patients with chronic hepatitis C who had undergone liver biopsy 1 to 2 weeks before interferon therapy and had started treatment between January 1992 and December 1993 . The control group consisted of 144 consecutive patients with chronic hepatitis or cirrhosis who had undergone liver biopsy between January 1986 and December 1989 . All patients had histologically proven chronic hepatitis or cirrhosis ( Child-Pugh class A ) and were positive for anti-HCV . Interferon Treatment In the interferon group , 176 patients received human lymphoblastoid interferon , 149 received recombinant interferon- 2a , and 94 received recombinant interferon- 2b for 6 months . The median total interferon dose was 480 mU ( range , 282 to 800 mU ) . No patient had received interferon therapy before study entry . Contraindications to interferon treatment included pregnancy , presence of hepatitis B surface antigen , other types of liver disease , autoimmune disease , and any other serious illness . Efficacy of interferon therapy was categorized as follows . Patients with persistent normalization of alanine aminotransferase ( ALT ) levels during interferon therapy and follow-up were considered to have sustained response . Patients whose serum ALT level was normal at the end of the treatment but increased to an abnormal level after cessation of treatment were considered to have relapse . All other patients were classified as nonresponders . Follow-up Abdominal ultrasonography or computed tomography was performed every 4 to 8 months , and serum -fetoprotein was measured every 2 to 6 months . The diagnosis of hepatocellular carcinoma was confirmed by needle biopsy , by surgically resected tumor specimens , or by typical radiologic findings on hepatic angiography . The starting date of follow-up for patients in the interferon and control groups was defined as the date of liver biopsy . For both groups , the end of follow-up was the development of hepatocellular carcinoma or December 1991 in the control group and the time of the latest abdominal imaging in the interferon group . To detect hepatocellular carcinoma , follow-up examinations were done in 85.4 % of controls and 90.7 % of patients in the interferon group . The Osaka Cancer Registry was used [ 21 , 22 ] to determine whether hepatocellular carcinoma had occurred in patients lost to follow-up . This population -based cancer registry has been operating since December 1962 with the cooperation of the Osaka Medical Association , the Department of Health of Osaka Prefecture , and Osaka Medical Center for Cancer and Cardiovascular Diseases . It covers all of Osaka Prefecture , which had a population of 8.6 million in 1995 , and registers cases of cancer by using reports from hospitals and clinics and death certificates collected from health centers . One patient in each group who had been lost to follow-up was listed as having hepatocellular carcinoma in the Osaka Cancer Registry . Determination of the Presence of Hepatitis C Virus Antibody and Hepatitis C Virus RNA Hepatitis C virus antibody was measured by first- , second- , or third-generation enzyme-linked immunosorbent assays ( Ortho Diagnostics , Tokyo , Japan ) . Serum HCV RNA was measured by reverse transcription polymerase chain reaction or complementary DNA assay , as reported elsewhere [ 23 , 24 ] . Assessment of Liver Histologic Findings The histologic findings in liver biopsy specimens were scored by three of the authors in a blinded manner by using two scoring methods . For assessment of histologic staging , fibrosis score ( F1 to F3 for chronic hepatitis and F4 for cirrhosis ) was used ; F1 indicated portal fibrous expansion , F2 indicated portal-portal septa without architectural distortion , F3 indicated porto central septa with architectural distortion , and F4 indicated cirrhosis [ 25 ] . For assessment of histologic grading , a total score of histologic activity ( components 1 to 3 ) of the Knodell histologic activity index was used [ 26 ] . Statistical Analysis Patients who did not complete the treatment protocol were included for analysis on an intention-to-treat basis . The chi-square test was used to compare the baseline characteristics of both groups . The Wilcoxon rank-sum test was used to assess a significant difference between tumor sizes in the two groups . The Kaplan-Meier method was used to calculate the cumulative incidence of hepatocellular carcinoma , and the log-rank test was used to compare the cumulative incidence of hepatocellular carcinoma between the groups . To estimate independent risk factors for the development of hepatocellular carcinoma , Cox proportional-hazards regression analysis was used . For analysis , interferon therapy , age , sex , serum ALT level , serum -fetoprotein level , platelet count , histologic staging , and activity scores were used as variables . A P value less than 0.05 was considered statistically significant . Data are expressed as medians and ranges and as risk ratios and 95 % CIs . Results Table 1 shows the baseline characteristics of the interferon and control groups . The groups did not differ for age , sex , serum ALT level , or platelet count . In the interferon group , 387 patients ( 92 % ) had chronic hepatitis ( 128 had F1 disease , 138 had F2 disease , and 121 had F3 disease ) and 32 ( 8 % ) had cirrhosis . In the control group , 124 patients ( 86 % ) had chronic hepatitis ( 30 had F1 disease , 38 had F2 disease , and 56 had F3 disease ) and 20 ( 14 % ) had cirrhosis ( P = 0.005 ) . The proportion of patients with serum -fetoprotein levels greater than 20 ng/mL was higher in the control group ( 24 % ) than in the interferon group ( 15 % ) ( P = 0.011 ) . Table 1 . Baseline Characteristics of Interferon-Treated Patients and Historical Controls with Chronic Hepatitis C In the interferon group , 151 patients ( 36 % ) had sustained response , 120 ( 29 % ) had relapse , and 148 ( 35 % ) were nonresponders . In the 143 patients with sustained response , serum HCV RNA was measured during follow-up . Sustained absence of serum HCV RNA was noted in 120 ( 84 % ) of these patients . Twenty-one patients could not complete the 6-month treatment protocol because of depression ( 5 patients ) , severe general fatigue ( 4 patients ) , skin eruptions ( 2 patients ) , severe reduction of serum platelet count ( 1 patient ) , pulmonary tuberculosis ( 1 patient ) , interstitial pneumonia ( 1 patient ) , severe nausea ( 1 patient ) , ischemic colitis ( 1 patient ) , cardiomyopathy ( 1 patient ) , hyperthyroidism ( 1 patient ) , and hypermenorrhea ( 1 patient ) . One patient stopped treatment because of his business , and one patient discontinued treatment after 3 months because hepatocellular carcinoma was diagnosed . Only 1 of the 21 patients who did not complete treatment showed sustained response ; all others were nonresponders . Median follow-up was 47.6 months ( range , 3.3 to 65.2 months ) in the interferon group and 46.8 months ( range , 6.9 to 71.6 months ) in the control group . During follow-up , hepatocellular carcinoma was found in 19 controls ( 4 with F2 disease , 8 with F3 disease , and 7 with F4 disease ) . In the interferon group , 28 patients developed hepatocellular carcinoma during follow-up ( 2 patients with F1 disease , 5 with F2 disease , 13 with F3 disease , and 8 with F4 disease ) . A final diagnosis of hepatocellular carcinoma was made histologically in 17 patients in the interferon group ( 61 % ) and 11 controls ( 58 % ) . In 11 patients ( 39 % ) in the interferon group and 8 controls ( 42 % ) , a final diagnosis was made on the basis of typical angiographic findings . The maximum tumor sizes of hepatocellular carcinoma in the interferon and control groups at the time of discovery on ultrasonography or computed tomography were 20 mm ( range , 10 to 52 mm ) and 24 mm ( range , 10 to 50 mm ) , respectively ( P > 0.2 ) . Figure 1 shows the cumulative incidence of hepatocellular carcinoma in the interferon and control groups , estimated by using the Kaplan-Meier method . The 4-year rate of hepatocellular carcinoma incidence was 6.6 % in the interferon group and 12.2 % in the control group ( log-rank test , P = 0.040 ) . Figure 1 . Cumulative incidence of hepatocellular carcinoma ( HCC ) in interferon-treated patients ( dotted line ) and historical controls ( solid line ) with chronic hepatitis C. P Cox proportional-hazards regression analysis was performed to identify factors Methods for combining data from several studies exist and appear to be quite useful . None satisfactorily addresses the question of what studies should be combined . This issue is the most serious method ological limitation . Even studies with statistically significant interaction might still be combined if the effect were in the same direction . Thus , substantial scientific input is required as to what criteria must be met by each potential study . Much can be learned from combining or pooling data but it must be done cautiously . Pooling exercises do not replace well design ed prospect i ve clinical trials . Efforts for establishing basic design criteria to allow for multicentre and multicountry trials to be more easily combined might be useful . Background : Fifty per cent of chronic hepatitis C patients are non-responders to interferon . At present , there are no recommended therapeutic options for non-responders . Aims : The safety and long term effect of alpha interferon induction plus ribavirin with or without amantadine in the treatment of interferon non-responsive chronic hepatitis C was evaluated . Patients and methods : A total of 114 consecutive patients were r and omly divided into three groups with a final 2:2:1 ratio : group A ( 44 patients ) received interferon alfa 2b , 3 million units ( MU ) , three times a week , and oral ribavirin ( 1000 mg/day ) ; group B ( 46 patients ) received interferon 3 MU daily for the first four weeks and subsequently 3 MU three times a week , and ribavirin as in regimen A ; and group C ( 24 patients ) received interferon and ribavirin as in regimen B , plus oral amantadine hydrochloride ( 200 mg/day ) . The duration of treatment was 12 months . Results : The end of treatment response for groups A and B was 25 % and 29 % , respectively , and for group C , 68 % ( p<0.005 ) . At the end of one year of follow up , a sustained response was observed for six ( 25 % ) patients in group C , one ( 2 % ) patient in group A , and two ( 4 % ) patients in group B ( p<0.002 ) . The triple regimen was well tolerated and did not increase the frequency or severity of side effects . Conclusions : The study demonstrates that for the treatment of interferon non-responder hepatitis C patients , the association of interferon-ribavirin has a negligible long term effect whereas a triple regimen including interferon , ribavirin , and amantadine can be an effective and safe treatment To evaluate leukocyte interferon alpha-n3 tolerability and efficacy in the retreatment of patients with chronic hepatitis C poorly tolerant to previous treatment with recombinant interferon alpha , 142 patients ( 73 " relapsers " and 69 " nonresponders " ) were retreated with leukocyte interferon alpha-n3 ( 6 MU thrice weekly for 6 months ) and followed up for 12 - 42 months . Only patients with complete regression of any previous interferon-related adverse events were included . Three patients dropped out due to recurrence of a severe depressive syndrome . In 104/139 patients ( 75 % ) no significant life-style changes vs baseline were observed during retreatment , while 35 subjects experienced moderately negative interference with their living habits . The different influence on the patients ' quality of life during leukocyte interferon alpha-n3 treatment in comparison with the previous treatment was significant . In 118 patients ( 85 % ) the interferon-related adverse events significantly decreased . After 12 months of follow-up , a sustained biochemical response was observed in 48 patients ( 35 % ) , and a persistent biochemical and virological response was seen in 33 ( 23 % ) . The good compliance with leukocyte interferon alpha-n3 administration shown by poorly tolerant patients , " relapsers/nonresponders " to recombinant interferon , permitted retreatment with full doses and thus increased the chance of obtaining a larger number of sustained responses We assessed the efficacy of interferon ( IFN ) plus ribavirin over 24 or 48 weeks for the retreatment of patients with chronic hepatitis C who had relapsed or did not respond to a previous course of IFN . One-hundred and twenty patients ( 69 non-responders and 51 relapsers ) were r and omly assigned to receive IFN-alpha2b ( 3 million units thrice weekly ) plus ribavirin ( 1,000 - 1,200 mg per day ) for 24 weeks ( group A : 58 patients ) or 48 weeks ( group B : 62 patients ) . Treatment was discontinued at week 12 if the alanine aminotransferase ( ALT ) level remained elevated . The rate of sustained response was 15.5 % in group A and 37.1 % in group B ( P = 0.013 ) . Relapsers treated for 48 weeks had a sustained response rate of 66.6 % compared with a sustained response rate of only 25 % in those treated for 24 weeks ( P = 0.004 ) . Moreover , a sustained response was seen in 14.3 % of non-responders treated for 48 weeks and in 8.8 % of those treated for 24 weeks ( P = 0.71 ) . Fifty-three per cent of patients with a normal ALT level and undetectable hepatitis C virus ( HCV ) RNA at week 12 had a sustained response compared with 14 % of those who were HCV RNA positive at week 12 ( P < 0.001 ) . Independent predictive factors of sustained response were : therapy for 48 weeks ( P = 0.0026 ) , relapse after IFN treatment ( P = 0.0006 ) , loss of HCV RNA at week 12 ( P = 0.0008 ) and HCV genotype non-1 ( P = 0.024 ) . Hence , in patients with chronic hepatitis C who failed to respond to a previous course of IFN monotherapy , combination therapy with IFN plus ribavirin for 48 weeks seems to be more effective than IFN plus ribavirin for 24 weeks BACKGROUND Treatment with peginterferon alfa-2a alone produces significantly higher sustained virologic responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus ( HCV ) infection . We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin , interferon alfa-2b plus ribavirin , and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. METHODS A total of 1121 patients were r and omly assigned to treatment and received at least one dose of study medication , consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin ( 1000 or 1200 mg , depending on body weight ) , weekly peginterferon alfa-2a plus daily placebo , or 3 million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks . RESULTS A significantly higher proportion of patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response ( defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy ) than of patients who received interferon alfa-2b plus ribavirin ( 56 percent vs. 44 percent , P<0.001 ) or peginterferon alfa-2a alone ( 56 percent vs. 29 percent , P<0.001 ) . The proportions of patients with HCV genotype 1 who had sustained virologic responses were 46 percent , 36 percent , and 21 percent , respectively , for the three regimens . Among patients with HCV genotype 1 and high base-line levels of HCV RNA , the proportions of those with sustained virologic responses were 41 percent , 33 percent , and 13 percent , respectively . The overall safety profiles of the three treatment regimens were similar ; the incidence of influenza-like symptoms and depression was lower in the groups receiving peginterferon alfa-2a than in the group receiving interferon alfa-2b plus ribavirin . CONCLUSIONS In patients with chronic hepatitis C , once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained virologic response , as compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone BACKGROUND / AIM Roughly 50 % of patients with chronic hepatitis C , who relapsed after a previous monotherapy with interferon alpha , will respond in a sustained fashion to 24 weeks of re-therapy with the combination of interferon alpha plus ribavirin . Whether prolonging treatment duration to 48 weeks will further increase sustained response rates remains ill defined . In this r and omised controlled pilot trial we compared the efficacy and tolerability of a 24 week with that of a 48 week course of combination therapy with interferon alpha and ribavirin in interferon monotherapy relapsers with chronic hepatitis C. METHODS Interferon alpha monotherapy relapsers with chronic hepatitis C were r and omised to receive interferon alpha 2b ( 3 x 3 MIU sc weekly ) and oral ribavirin ( 1000/1200 mg po daily ) for either 24 weeks or 48 weeks . Virological response was evaluated by HCV RNA PCR at week 10 ( initial response ) , at the end of treatment ( end of- treatment response ) and at the end of 24 weeks follow-up ( sustained response ) . Only patients with negative HCV RNA at week 10 continued treatment . Adverse events were recorded at regular intervals . RESULTS Thirty-seven patients were enrolled , 19 ( 6 females , median age 43 ) in the 24 week and 18 ( 5 females , median age 40 ) in the 48 week treatment arm . Baseline characteristics were similar in both groups . At treatment week 10 , 12/19 ( 63 % ) in the 24 week group and 14/18 ( 78 % ) patients in the 48 week group had lost HCV RNA in serum ( p = 0.33 ) . All initial responders remained HCV RNA negative throughout the treatment period . Sustained response rates were 10/19 ( 53 % ) in the 24 week group and 13/18 ( 72 % ) in the 48 week group ( p = 0.31 ) . Three patients discontinued treatment early ( two due to moderate adverse events , one due to non-compliance ) . Dose modifications were necessary in 9 patients , 4 in the 24 week and 5 in the 48 week group for anaemia , neutropenia , nausea and depression , respectively . CONCLUSION Prolonging interferon / ribavirin combination therapy in interferon alpha monotherapy relapsers with chronic hepatitis C from 24 to 48 weeks may increase sustained response rates . Larger controlled trials using pegylated interferon alpha and ribavirin in relapsers with chronic hepatitis C seem warranted Hepatitis C virus ( HCV ) infection rarely resolves spontaneously once it becomes chronic ( 1 ) . Most patients remain asymptomatic for a long period , with liver cirrhosis developing after approximately 30 years ( 2 , 3 ) . Chronic hepatitis C with cirrhosis is a major risk factor for hepatocellular carcinoma ( 4 - 7 ) . It has been previously shown that the risk increases with the degree of liver fibrosis ( 5 ) . Interferon is the only agent known to be effective against HCV infection ( 8 - 10 ) . It induces a sustained virologic response in 15 % to 30 % of patients ( 11 - 14 ) . Responders usually show biochemical and histologic improvement ( 9 , 11 , 15 ) . Recently , interferon therapy in patients with chronic hepatitis C and cirrhosis was shown to be associated with a reduced incidence of hepatocellular carcinoma ( 16 ) . Because most patients treated with interferon do not have cirrhosis , we included noncirrhotic as well as cirrhotic patients in our analysis of the effect of interferon therapy on the incidence and prevention of hepatocellular carcinoma . A national surveillance program , the Inhibition of Hepatocarcinogenesis by Interferon Therapy ( IHIT ) Study , was begun in 1994 as a multicenter , large-scale , retrospective cohort study supported by the Japan Ministry of Health and Welfare as one of the Comprehensive 10-Year Strategy for Cancer Control Projects ( 17 ) . In this program , patients with chronic hepatitis C who have undergone liver biopsy at one of eight participating institutions are enrolled and followed periodically for development of hepatocellular carcinoma by using several imaging techniques . We analyzed the incidence of hepatocellular carcinoma as of February 1998 by using multivariate proportional hazards regression . Methods Patients The IHIT Study Group approved the design of this study on 21 September 1994 . All patients who were positive by a second-generation HCV antibody assay and who had undergone liver biopsy since 1986 at one of the eight participating institutions were enrolled . Patients who were participants in interferon trials for non-A , non-B chronic hepatitis ( 18 - 21 ) and in whom anti-HCV seropositivity was confirmed by using stored sera were also included ; these patients had undergone liver biopsy in 1986 or later . Patients were excluded if at the time of liver biopsy they presented with hepatocellular carcinoma or other liver diseases , such as chronic hepatitis B , alcoholic liver disease , autoimmune hepatitis , or primary biliary cirrhosis . The minimum follow-up was established as 1 year for two reasons . First , if hepatocellular carcinoma is detected within 1 year after liver biopsy , the possibility that the cancer was present at the time of liver biopsy can not be ruled out . Second , interferon therapy must be started within 1year after liver biopsy according to Japanese health insurance rules . By February 1998 , 3223 patients who fulfilled the inclusion criteria were registered . Of these patients , 333 were excluded from the analysis : 161 patients ( 5.0 % ) transferred to other hospitals without follow-up , and the follow-up period after liver biopsy was less than 1 year for172 patients ( 5.3 % ) . Thus , 2890 patients were included in the present analysis . Figure 1 shows the schema for patient selection . Figure 1 . Schema for patient selection . Interferon therapy was given to 2400 patients ; 490 patients did not receive treatment ( control group ) . Interferon therapy was initiated within 1 year after liver biopsy ( within 6 months in 93 % of patients ) ; 84 % of patients received interferon- , 14 % received interferon- , and 2 % received a combination of interferon- and interferon- . The median total dose was 480 MU ( first quartile , 324 MU ; third quartile , 702 MU ) , and the median duration of administration was 160 days(first quartile , 94 days ; third quartile , 168 days ) . Once interferon therapy was started , a patient was included in the interferon treatment group even if therapy was discontinued because of adverse events or other reasons . The 490 patients who did not receive interferon chose this course of action voluntarily on the basis of concerns about adverse effects ; lack of time for therapy ; or physician recommendation , which took into account depression , severe diabetes mellitus , or other medical conditions . Serum HCV load was quantitatively determined at the timeof liver biopsy by using various commercial and in-house assays . Because it is difficult to correlate the results of different assay methods , only data obtained with two widely used assays , the branched-DNA probe assay ( 22 ) and competitive reverse-transcription polymerase chain reaction ( RT-PCR ) ( 23 ) , were used . HCV RNA genotype was determined by RT-PCR using genotype-specific primers ( 24 ) or by serologic grouping of serum antibody ( 25 ) , assuming that genotypes 1a and 1b correspond to serologic group 1 ( genotype 1 ) and genotypes 2a and 2b correspond to serologic group 2 ( genotype 2 ) ( 11 ) . Histologic Evaluation Liver biopsy specimens were evaluated by a representative pathologist at each institution ( a total of eight pathologists were involved ) and were scored for the stage of liver fibrosis and grade of inflammatory activity according to the classification of Desmet and colleagues ( 26 ) . Stage of fibrosis was assessed from stage F0 ( no fibrosis ) to stage F4 ( cirrhosis ) , and grade of inflammatory activity was scored from grade A1 ( mild ) to grade A3 ( severe ) . To confirm interobserver concordance in scoring , a subsequent blind and independent examination of 350r and omly selected liver biopsy specimens was conducted by two of the eight pathologists . Definition of Interferon Response Virologic and biochemical criteria were used to define response to interferon therapy . Hepatitis C virus RNA was used as a marker of virologic response and was determined by RT-PCR . A virologic sustained response was defined as HCV RNA negativity more than 6 months after termination of interferon therapy ; positivity at the same time point was considered a nonsustained response ( 27 ) . Patients with nonsustained response included those who had temporary disappearance of viremia followed by relapse . In patients treated before the availability of RT-PCR , virologicresponse was determined by using sera stored at 30 C or collected afterward . The serum alanine aminotransferase ( ALT ) level was used as a marker of biochemical response to interferon therapy . Sustained biochemical response was defined as persistently normal serum ALT levels more than 6 months after termination of interferon therapy ; nonsustained response was defined as elevated serum ALT levels at the same time point . Nonsustained response was subdivided into two categories : mildly elevated for a serum ALT level less than two times the upper limit of normal and highly elevated for a serum ALT level two or more times the upper limit of normal . Screening for Hepatocellular Carcinoma Patients were examined for hepatocellular carcinoma by abdominal ultrasonography at least every 6 months . If hepatocellular carcinoma was suspected on the basis of ultrasonographic results , additional procedures , such as computed tomography , magnetic resonance imaging , abdominal angiography , and ultrasonography-guided tumor biopsy , were used to confirm the diagnosis . Statistical Analysis Statistical analysis was performed by using SAS software , version 6.12 ( SAS Institute , Inc. , Cary , North Carolina ) . Interobserver concordance of histologic scoring was evaluated by using the Spearman correlation coefficient . Differences between two groups were evaluated by using the unpaired Student t-test or the Mann-Whitney U-test . Categorical data were compared by using the chi-square test or the Fisher exact probability test . Cumulative incidence curves were determined with the Kaplan-Meier method , and the differences between groups were assessed by using the log-rank test . We used the Cox proportional-hazards regression analysis to examine the effect of interferon therapy on the incidence of hepatocellular carcinoma . Because virologic and biochemical responses were mutually dependent , the risk ratio for hepatocellular carcinoma was calculated separately for these factors . The risk ratio attributable to categorical data , such as stage of liver fibrosis and serum ALT level , was calculated by using dummy variables . A P value less than 0.05 was considered statistically significant . Results Patient Characteristics The demographic and clinical features of patients at the time of their enrollment are summarized in Table 1 . The frequency distribution of the stages of liver fibrosis differed between interferon-treated patients and untreated patients . Most laboratory values also differed between the two groups . However , differences in laboratory values between treated patients and untreated patients were not significant at the same stage of fibrosis . This indicated the need to adjust for stage of liver fibrosis , which was done in the following analyses . Table 1 . Demographic and Clinical Characteristics Histologic Evaluation The concordance in scores for stage of fibrosis and grade of inflammatory activity determined at each institution and by the two representative pathologists was strong , with Spearman coefficients ranging from 0.897 to 0.918 for stage of fibrosis and from 0.878 to 0.849 for grade of inflammatory activity . The original score was sustained by at least one of the two pathologists in 319 of 350 cases for fibrosis staging and in 320 of 350cases for grading inflammatory activity . Response to Interferon Therapy Response to interferon therapy was determined in 2357(98.2 % ) of the 2400 interferon-treated patients . Response was not determined in43 patients because of insufficient follow-up ( < 6 months ) after termination of therapy . A sustained virologic response was achieved in 789 patients ( 33.5 % ) . The response rate was similar regardless of the type of interferon used ( 32.3 % , 34.5 % , and 25.6 % for interferon- , interferon- , and the combination of the two , respectively ) . A sustained BACKGROUND Recently , the combination treatment of recombinant alpha-interferon plus ribavirin has been proposed for chronic hepatitis C patients unresponsive to previous therapy with recombinant alpha-interferon alone . AIM To determine the effectiveness of the combination therapy for the re-treatment of chronic hepatitis C patients unresponsive to previous interferon therapy . Immediate and long-term follow-up data are reported . PATIENTS AND METHODS A series of 100 patients with chronic hepatitis C not responding to recombinant alpha-interferon 3 MU tiw , were r and omly assigned to two groups of 50 patients each : Group A , treated with recombinant alpha-interferon therapy for an additional six months but at a double dosage ( 6 MU tiw ) in association with ribavirin . Group B , same treatment as group A but without ribavirin . All patients responsive to therapy were then followed-up for at least 12 months . At the end of the treatment and at the end of the follow-up period , we distinguished between complete responses ( return to normal of alanine aminotransferase with undetectable serum HCV-RNA ] and biochemical responses ( return to normal of alanine aminotransferase still with detectable viraemia ) . RESULTS Side-effects were observed only in patients treated with recombinant alpha-interferon plus ribavirin : 12 % discontinued the therapy due to haemolytic anaemia . In group A , the percentages of end-of-treatment complete response , end-of-treatment biochemical response , sustained complete response , and sustained biochemical response , were 38 % , 20 % , 8 % , and 14 % , respectively , whilst in group B , these percentages were 12 % , 16 % , 6 % , and 16 % , respectively . CONCLUSION The results indicate that in patients with chronic hepatitis C unresponsive to previous recombinant alpha-interferon therapy , re-treatment with higher recombinant alpha-interferon doses , either alone or in combination with ribavirin , lead to mild long-term benefit . However , the satisfactory end of treatment complete response in group A suggests that a significant percentage of patients are sensitive to the combination therapy ; and that a more aggressive therapeutic protocol in this selected subset of patients could result in a larger number of long-lasting responses leading , in turn , to a more favourable cost-effect ratio A multicenter , open-label , phase 3 study was conducted in 337 patients with chronic hepatitis C virus ( HCV ) infection who had either not responded to previous interferon therapy or had relapsed after discontinuation of therapy with either consensus interferon ( 9 microg ) or interferon alpha-2b ( 3 million U ) three times a week for 24 weeks . Patients were r and omized to receive a higher dose of consensus interferon ( 15 microg ) administered subcutaneously three times a week for 24 or 48 weeks and then were observed for an additional 24 weeks . Patients who had relapsed after prior interferon therapy were more likely to have a sustained alanine aminotransferase response and HCV RNA response ( as measured by reverse transcription-polymerase chain reaction with a sensitivity of < 100 copies/mL ) than were patients who had not responded to prior interferon therapy . For relapsers , the sustained HCV RNA response rate was 58 % ( 48 weeks ) and 28 % ( 24 weeks ) . The sustained alanine aminotransferase response for relapsers was 52 % ( 48 weeks ) and 39 % ( 24 weeks ) . The sustained HCV RNA response rate among prior nonresponders was 13 % ( 48 weeks ) and 5 % ( 24 weeks ) , and the sustained alanine aminotransferase response rate for nonresponders was 17 % ( 48 weeks ) and 12 % ( 24 weeks ) . The administration of 15 microg of consensus interferon was well tolerated and was not associated with an increase in the incidence of side effects . These data demonstrate that re-treatment with 15 microg of consensus interferon is safe and effective therapy for patients with chronic hepatitis C who have either not responded to previous interferon therapy or relapsed after discontinuation of interferon therapy BACKGROUND Preliminary results from combination therapy with interferon-alpha and ribavirin ( IFN/Rib ) in patients with chronic hepatitis C have been promising , with up to 50 % sustained hepatitis C virus ( HCV ) RNA response . The aim of this study was to investigate whether a sustained HCV RNA response could be obtained with combination therapy in patients who were non-responders or relapsers after IFN treatment . METHODS In a multicenter study we r and omized 53 HCV RNA-positive patients into 2 treatment groups . They all had biopsy-confirmed chronic hepatitis C , and all were recruited from a previous IFN study : 26 were previous non-responders and 27 responders with relapse . Group A received interferon-alpha2a , 4.5 MIU thrice weekly for 6 months , and group B received ribavirin , 1000 - 1200 mg/day , in combination with the same dose of interferon-alpha2a for 6 months . Median Knodell index was 5.0 in both groups . Genotype 1 was found in 24 ( 45 % ) , type 2 in 3 ( 6 % ) , and type 3 in 26 ( 49 % ) . RESULTS Sustained clearance of HCV viremia 6 months after interferon-alpha2a treatment stop was obtained in 12 of 53 patients ( 23 % ) : 6 of 27 in the IFN group ( 22 % ) and 6 of 26 ( 23 % ) in the IFN/Rib group ( NS ) . Nine of 27 ( 33 % ) former responders with relapse , compared with 3 of 26 ( 12 % ) non-responders , obtained a sustained HCV RNA response ( P = 0.054 ) . In previous relapse patients sustained loss of viremia was more frequent in genotype 3 ( 50 % ) than in genotype 1 ( 11 % ) patients ( P = 0.022 ) . CONCLUSIONS In a group of previous IFN-alpha2a-treated chronic HCV patients we obtained a similar sustained clearance of viremia when retreated either with IFN-alpha2a alone or with a combination of IFN-alpha2a and ribavirin for 6 months . Previous relapse patients with HCV genotype 3 obtained sustained loss of viremia significantly more often ( 50 % ) than type- patients ( 11 % ) . Previous IFN responders with relapse responded better than previous non-responders Twenty-four patients with chronic active HCVinfection , nonresponders to a previous treatment cyclewith recombinant interferon-α ( r-IFNA ) , underwentretreatment with leukocyte ( LE- ) IFN-α . This was administered at the dose of 3 MU threetimes a week , for either six months ( group A ) or 12months ( group B ) . All patients were followed-up for afurther 12 months . ALT levels significantly ( P < 0.05 ) decreased in group A , with complete response inthree cases and a partial response in a further three atthe end of treatment . During follow-up all patients again showed increases in ALT values . In group B also ALT significantly ( P < 0.05)decreased , with two complete and five partial responses . During follow-up , apart from two patients with partialresponses who relapsed , all maintained their initial response . At the end of treatment HCV RNA wasno longer detectable in complete responders of bothgroups , while it was found reduced in those partialresponders who maintained their response duringfollow-up . Partially responding subjects treated for sixmonths evidence d higher levels than those treated for 12months . IFN-α retreatment could therefore beeffective in previously nonresponding patients , with a change in the type of interferon administered and the use of higher dosages and /or longer treatmentperiods BACKGROUND In phase 2 trials , telaprevir , a hepatitis C virus ( HCV ) genotype 1 protease inhibitor , in combination with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , has shown improved efficacy , with potential for shortening the duration of treatment in a majority of patients . METHODS In this international , phase 3 , r and omized , double-blind , placebo-controlled trial , we assigned 1088 patients with HCV genotype 1 infection who had not received previous treatment for the infection to one of three groups : a group receiving telaprevir combined with peginterferon alfa-2a and ribavirin for 12 weeks ( T12PR group ) , followed by peginterferon-ribavirin alone for 12 weeks if HCV RNA was undetectable at weeks 4 and 12 or for 36 weeks if HCV RNA was detectable at either time point ; a group receiving telaprevir with peginterferon-ribavirin for 8 weeks and placebo with peginterferon-ribavirin for 4 weeks ( T8PR group ) , followed by 12 or 36 weeks of peginterferon-ribavirin on the basis of the same HCV RNA criteria ; or a group receiving placebo with peginterferon-ribavirin for 12 weeks , followed by 36 weeks of peginterferon-ribavirin ( PR group ) . The primary end point was the proportion of patients who had undetectable plasma HCV RNA 24 weeks after the last planned dose of study treatment ( sustained virologic response ) . RESULTS Significantly more patients in the T12PR or T8PR group than in the PR group had a sustained virologic response ( 75 % and 69 % , respectively , vs. 44 % ; P<0.001 for the comparison of the T12PR or T8PR group with the PR group ) . A total of 58 % of the patients treated with telaprevir were eligible to receive 24 weeks of total treatment . Anemia , gastrointestinal side effects , and skin rashes occurred at a higher incidence among patients receiving telaprevir than among those receiving peginterferon-ribavirin alone . The overall rate of discontinuation of the treatment regimen owing to adverse events was 10 % in the T12PR and T8PR groups and 7 % in the PR group . CONCLUSIONS Telaprevir with peginterferon-ribavirin , as compared with peginterferon-ribavirin alone , was associated with significantly improved rates of sustained virologic response in patients with HCV genotype 1 infection who had not received previous treatment , with only 24 weeks of therapy administered in the majority of patients . ( Funded by Vertex Pharmaceuticals and Tibotec ; ADVANCE Clinical Trials.gov number , NCT00627926 . ) BACKGROUND & AIMS The impact of interferon ( IFN ) treatment on the occurrence of complications related to hepatitis C virus (HCV)-related cirrhosis is debated because the majority of studies are retrospective . We design ed a r and omized controlled trial comparing the efficacy of prolonged IFN alfa-2a treatment vs nontreatment on complication-free survival in patients with compensated HCV cirrhosis . METHODS A total of 102 patients ( mean age , 60.5 + /- 9.5 y ; male/female ratio , .82 ) with biopsy examination-proven HCV cirrhosis , Child-Pugh score A , who were hepatocellular carcinoma ( HCC ) free , and had at least 1 risk factor of complications were r and omized to receive IFN or no therapy for 24 months . RESULTS During the follow-up evaluation , the complication rate was 24.5 % : HCC occurred in 12 and decompensation unrelated to HCC occurred in 13 patients . The number of HCC patients was similar in both groups . The probability of complication-free survival was not significantly different between treated and untreated patients ( 98 % and 72.3 % vs 90 % and 70.7 % at 12 and 24 mo , respectively , P = .59 ) . The median time until complication occurrence was 17.1 months in the treated group vs 13.6 months in the untreated group ( P = .2 ) . CONCLUSIONS This r and omized controlled trial showed that a 2-year course of IFN has little or no impact on complication-free survival in patients with high-risk compensated HCV cirrhosis To compare the efficacy of low and relatively high dosages of recombinant interferon (IFN)-alpha-2a in Japanese patients with chronic hepatitis C , as well as to characterize the type of patients who will respond well to a low-dosage treatment , 88 patients with histologically proven chronic hepatitis C were r and omly assigned to two treatment groups ; one treated with IFN-alpha-2a 6 MU daily for 2 weeks followed by 6 MU three times weekly for 22 weeks ( 6-MU group ) , and another given the same initial treatment followed by 3 MU three times weekly for 22 weeks ( 3-MU group ) . The rate of sustained normalization of ALT 6 months after the cessation of treatment was 33 % in the 3-MU group and 40 % in the 6-MU group ( p = 0.64 ) . In addition , there was no difference in elimination of serum HCV-RNA 6 months after the cessation of treatment between the 3-MU group ( 26 % ) and 6-MU group ( 29 % ) . Multivariate stepwise regression analysis revealed that serum HCV-RNA level ( p = 0.0035 ) and platelet count ( p = 0.0009 ) were independent variables useful in predicting a sustained response of ALT . The sustained response rate of ALT in patients with a serum HCV-RNA level less than 10(5 ) copies/ml and serum platelet level above 15 x 10(4)/microliter was 71 % , whereas that in patients with a serum HCV-RNA level above 10(5 ) copies/ml and serum platelet level less than 15 x 10(4)/microliter was 12 % . These results indicate that a high rate of sustained response to IFN therapy can be expected in chronic hepatitis C patients with a low serum level of HCV-RNA and a high level of platelets , even if treated with a low dose of IFN BACKGROUND Covalent attachment of a 40-kd branched-chain polyethylene glycol moiety to interferon alfa-2a results in a compound ( peginterferon alfa-2a ) that has sustained absorption , a slower rate of clearance , and a longer half-life than unmodified interferon alfa-2a . We compared the clinical effects of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with chronic hepatitis C. METHODS We r and omly assigned 531 patients with chronic hepatitis C to receive either 180 microg of peginterferon alfa-2a subcutaneously once per week for 48 weeks ( 267 patients ) or 6 million units of interferon alfa-2a subcutaneously three times per week for 12 weeks , followed by 3 million units three times per week for 36 weeks ( 264 patients ) . All the patients were assessed at week 72 for a sustained virologic response , defined as an undetectable level of hepatitis C virus RNA ( < 100 copies per milliliter ) . RESULTS In the peginterferon group , 223 of the 267 patients completed treatment and 206 completed follow-up . In the interferon group , 161 of the 264 patients completed treatment and 154 completed follow-up . In an intention-to-treat analysis in which patients who missed the examination at the end of treatment or follow-up were considered not to have had a response at that point , peginterferon alfa-2a was associated with a higher rate of virologic response than was interferon alfa-2a at week 48 ( 69 percent vs. 28 percent , P=0.001 ) and at week 72 ( 39 percent vs. 19 percent , P=0.001 ) . Sustained normalization of serum alanine aminotransferase concentrations at week 72 was also more common in the peginterferon group than in the interferon group ( 45 percent vs. 25 percent , P=0.001 ) . The two groups were similar with respect to the frequency and severity of adverse events , which were typical of those associated with interferon alfa . CONCLUSIONS In patients with chronic hepatitis C , a regimen of peginterferon alfa-2a given once weekly is more effective than a regimen of interferon alfa-2a given three times weekly OBJECTIVES Combination therapy using peginterferon alfa-2a ( 40 kD ) plus ribavirin achieves viral eradication in nearly 60 % of patients with chronic hepatitis C viral infection . However , because of the numerous side effects , use of the combination regimen might be restricted for patients consulting private practitioners specialized in hepatogastroenterology . PATIENTS AND METHOD Conducted in this specific context , this prospect i ve clinical trial investigated the safety and efficacy of combination therapy in 197 patients . Therapy was given in compliance with the recommendations of the French consensus conference on hepatitis C treatment . RESULTS Commonly reported adverse effects were noted in 90 % of patients , most occurring during the first three months , with a stable prevalence thereafter and resolution after treatment end . The most frequent adverse events were asthenia ( 35 to 37.5 % according to the treatment group pruritus ( 25 to 26.3 % ) and flu-like syndrome ( 19 to 21.7 % ) . A depressive syndrome was reported in 20 to 21 % of patients . Grade 4 neutropenia was exceptional and never led to severe infections . At intent-to-treat analysis , the rate of sustained virological response was 54.8 % for the entire population . It was 71.1 % for patients with genotypes 2 or 3 ( mainly treated for 24 weeks ) and 44.6 % for patients with genotype 1 ( all treated 48 weeks ) . CONCLUSION The characteristic features of combination therapy observed in the context of private hepatogastroenterology consultations are similar to those observed in r and omized clinical trials To evaluate response rates to 3 , 5 , or 10 million units ( MU ) of interferon alfa-2b , given thrice weekly , and to determine whether higher doses of interferon increase the likelihood or durability of the response , a multicenter , r and omized trial was performed at nine academic medical centers in the United States . Two hundred forty eight patients with chronic hepatitis C were r and omized to receive 3 , 5 , or 10 MU of interferon alfa-2b thrice weekly for 12 weeks . Based on the alanine aminotransferase ( ALT ) response at treatment-week 12 , the patients were rer and omized to additional therapy at the same or at increased doses for an additional 12 to 36 weeks ; in the case of no response to the highest dose , the patients were discontinued from the study . Serum ALT concentrations and liver histology were measured . The overall complete response rates to 3 , 5 , or 10 MU were not different at treatment-week 12 ( 31 % vs. 42 % vs. 40 % , not significant ) . The majority of week-12 responders continued to respond during additional treatment . When the treatment was discontinued , 15.4 % to 19.0 % of patients maintained their response . Of the nonresponders to 3 MU at week 12 , who were continued on 3 MU for an additional 12 weeks , none responded . However , response to additional therapy occurred in 12 % of week-12 nonresponders , whose dose was escalated from 3 or 5 MU to 10 MU . The only baseline features associated with the treatment response were the absence of fibrosis or cirrhosis on the pretreatment liver biopsy and viral genotype . We conclude that the initial response to interferon in patients with chronic hepatitis C is not increased by treatment with higher doses of the drug . Patients who do not respond to 3 MU by treatment-week 12 will not respond with continued therapy at that dose ; however , a proportion of patients who do not respond to 12 weeks of treatment with 3 or 5 MU may respond to higher doses . Although the long-term sustained response rates are marginally increased with interferon doses above 3 MU three times per week , the side effects are difficult to tolerate . The analysis of baseline factors in relation to response identified no single baseline factor associated with a low-enough response rate to warrant withholding interferon therapy from patients with chronic hepatitis SUMMARY Beside substantial progress in treatment of chronic hepatitis C ( CHC ) particular patients ( genotype 1/4 , high viral load , previous nonresponse , cirrhosis ) remain difficult to treat . The aim of our pilot r and omized study was to compare efficacy and tolerability of st and ard doses of Peginterferon alpha-2b + ribavirin with higher doses of Peginterferon alpha-2b administered twice weekly + ribavirin . Sixty-five out patients with CHC were subsequently enrolled . Group A ( n = 22 ) received recommended doses of Peginterferon alpha-2b and group B ( n = 43 ) , received high doses twice weekly . Groups were comparable for baseline characteristics . All genotype 1/4 patients had high baseline viraemia . Sustained virological response ( SVR ) was significantly higher in group B among naïve patients ( 72%vs 25 % , P = 0.024 ) . A significantly higher rate of SVR was observed in group B both considering only genotype 1/4 patients , ( 46%vs 13 % , P = 0.03 ) and grouping together genotype 1/4 naive and relapsers ( 57%vs 11 % , P = 0.039 ) . Discontinuation rate was 32 % ( 7 of 22 ) in group A and 21 % ( 9 [ corrected ] of 43 ) in group B. Our response rates are the highest reported for genotype 1/4 with high viraemia . Our pilot study supports the need of r and omized studies to evaluate both viral kinetics and efficacy of high dose and twice weekly administration of Peginterferon alpha-2b in genotype 1/4 patients with high viraemia who may need personalized treatment schedules BACKGROUND In patients with chronic hepatitis C who do not have a response to antiviral treatment , the disease may progress to cirrhosis , liver failure , hepatocellular carcinoma , and death . Whether long-term antiviral therapy can prevent progressive liver disease in such patients remains uncertain . METHODS We conducted a r and omized , controlled trial of peginterferon alfa-2a at a dosage of 90 microg per week for 3.5 years , as compared with no treatment , in 1050 patients with chronic hepatitis C and advanced fibrosis who had not had a response to previous therapy with peginterferon and ribavirin . The patients , who were stratified according to stage of fibrosis ( 622 with noncirrhotic fibrosis and 428 with cirrhosis ) , were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after r and omization . The primary end point was progression of liver disease , as indicated by death , hepatocellular carcinoma , hepatic decompensation , or , for those with bridging fibrosis at baseline , an increase in the Ishak fibrosis score of 2 or more points . RESULTS We r and omly assigned the patients to receive peginterferon ( 517 patients ) or no therapy ( 533 patients ) for 3.5 years . The level of serum aminotransferases , the level of serum hepatitis C virus RNA , and histologic necroinflammatory scores all decreased significantly ( P<0.001 ) with treatment , but there was no significant difference between the groups in the rate of any primary outcome ( 34.1 % in the treatment group and 33.8 % in the control group ; hazard ratio , 1.01 ; 95 % confidence interval , 0.81 to 1.27 ; P=0.90 ) . The percentage of patients with at least one serious adverse event was 38.6 % in the treatment group and 31.8 % in the control group ( P=0.07 ) . CONCLUSIONS Long-term therapy with peginterferon did not reduce the rate of disease progression in patients with chronic hepatitis C and advanced fibrosis , with or without cirrhosis , who had not had a response to initial treatment with peginterferon and ribavirin . ( Clinical Trials.gov number , NCT00006164 . To determine whether a higher dosage of interferon ( IFN ) associated with ribavirin and /or prolonged time of administration may improve therapeutic efficacy , we conducted a 4-arm r and omized trial on patients with chronic hepatitis C not responding to one or more previous treatment courses with IFN monotherapy . Group 1 ( n = 139 ) received 3 million units ( MU ) IFN-alpha2b 3 times a week ( t.i.w . ) plus ribavirin 1,000 mg/d for 12 months ; group 2 ( n = 162 ) received 5 MU t.i.w . plus ribavirin for 12 months ; group 3 ( n = 142 ) received 3 MU t.i.w . plus ribavirin for 6 months ; and group 4 ( n = 151 ) received 5 MU t.i.w . plus ribavirin for 6 months . The primary end point was hepatitis C virus (HCV)-RNA clearance at the end of 6-month follow-up . HCV-RNA was negative in 15 % of group 1 , 23 % of group 2 , 11 % of group 3 , 16 % of group 4 ( group 2 vs. group 3 , P = .04 ) . Among patients with genotypes 1 and 4 , sustained response was significantly higher in group 2 vs. group 3 ( 18 % vs. 7 % , P = .03 ; group 1 = 9 % , group 4 = 12 % , P = not significant [ NS ] ) . In patients with genotypes 2 and 3 , sustained virologic response was not affected by the different regimens ( group 1 = 32 % , group 2 = 30 % , group 3 = 30 % , group 4 = 35 % , P = NS ) . In conclusion , about 23 % of nonresponders to IFN monotherapy may achieve a sustained response if re-treated by 5 MU t.i.w . IFN plus ribavirin 1,000 mg/d for 1 year . Patients with genotype 1 should receive a high dosage of IFN plus ribavirin for 12 months , whereas therapy for patients with genotype 2 or 3 should be less aggressive Patients with chronic hepatitis C who are infected with hepatitis C virus of genotype 1b and have a high viral load in serum ( > 1 Mega equivalents/ml ) poorly respond to interferon with the st and ard regimen . Natural interferon-alpha ( nIFN-alpha : OPC-18 ) was given to 106 such patients r and omized into two different therapeutic schedules . One group consisting of 53 patients received daily intramuscular injection with 10 mega units ( Meq ) for 2 - 4 weeks and then 5 Meq three times per week until 24 weeks and the other group of 53 patients were placed on the same regimen until 48 weeks . At 24 weeks after the completion of therapy , HCV RNA turned negative in 11 ( 25 % ) patients with the 48-week therapy , significantly more frequently than in two ( 5 % ) patients with the 24-week therapy ( P=0.014 ) . There were no differences in the incidence and severity of adverse effects between the patients who received 24- and 48-week nIFN-alpha . Based on these results , nIFN-alpha with a high-dose induction and extended to 48 weeks would be a reasonable therapeutic option for the patients infected with HCV/1b in high viral loads who do not respond to the st and ard regimen with a 24-week schedule BACKGROUND / AIMS In chronic hepatitis C , interferon alfa ( IFN-alpha ) therapy fails to achieve a sustained response in approximately 75 % of patients . Similarly , ribavirin induces only a transient response . The aim of this study was to evaluate whether ribavirin and IFN-alpha in combination could be effective in IFN-alpha-resistant chronic hepatitis C. METHODS Twenty patients with chronic hepatitis C resistant to a previous course of IFN-alpha were r and omly assigned to receive either ribavirin combined with IFN-alpha or IFN-alpha alone for 6 months . RESULTS Serum alanine aminotransferase levels decreased significantly during therapy in both treatment groups , but after therapy , the levels remained significantly decreased only in the combination therapy group . Nine months after treatment , sustained normalization of aminotransferase levels , associated with sustained loss of serum hepatitis C virus RNA , was observed in 40 % of the patients in the combination therapy group but in none of the patients treated with IFN-alpha alone ( P < 0.05 ) . The sustained response was accompanied by reduced hepatic necroinflammatory activity on biopsy . CONCLUSIONS These findings suggest that ribavirin plus IFN-alpha combination therapy is able to induce a sustained biochemical and virological response in a significant proportion of patients with IFN-alpha-resistant chronic hepatitis BACKGROUND / AIMS Few data are available concerning the short and long-term effects of beta-IFN in patients with chronic hepatitis C. METHODOLOGY We r and omized 61 consecutive patients with HCV-related cirrhosis to receive : a ) natural beta-IFN with a 6 MU/tiw for 6 months followed by 3 MU/tiw for 6 months schedule or b ) no treatment . Biochemical and virological response was defined by normalization of ALT and negativization of serum HCV-RNA . Patients were followed-up for 5 years . RESULTS A biochemical end-of-therapy response ( ETR ) was observed in 5/38 patients ( 13 % ) who received beta-IFN compared to 2/23 ( 9 % ) of untreated cases , but a virological ETR appeared only in 4/38 ( 11 % ) treated cases . At long-term follow-up , 6 cases ( 16 % ) who received beta-IFN and 4 untreated ( 17 % ) developed a persistent normalization of alanine aminotransferase ( ALT ) but only 2 ( 5 % ) and 1 ( 4 % ) , respectively , were also HCV-RNA negative . The cumulative probability of liver decompensation ( variceal bleeding ascites or hepatic encephalopathy ) at 60 months was 24 % in treated and 35 % in untreated cases . Hepatocellular carcinoma developed in 2 treated and in 1 untreated patients . CONCLUSIONS beta-IFN therapy was not associated with a significant improvement either in biochemical or virological response in cirrhotic patients with chronic hepatitis C. No significant reduction of cirrhosis related clinical events was linked to treatment BACKGROUND The efficacy of consensus interferon ( CIFN ) , a synthetic IFN with optimised in vitro activity , was assessed in chronic hepatitis C virus ( HCV ) patients who had failed the pretreatment with interferon-alpha ( IFNalpha ) and ribavirin . METHODS One hundred and three patients after non-response ( n=69 ) or relapse ( n=34 ) to IFNalpha+/-ribavirin were r and omly assigned to high-dose induction ( CIFN 27 - ->9 microg daily for 24 weeks , 9 microg t.i.w . for 24 weeks ) or low-dose treatment ( CIFN 18 microg t.i.w . for 12 weeks , 9 microg t.i.w . for 36 weeks ) ; each with ribavirin 800 mg/day . Follow-up was 24 weeks . RESULTS Non-responder patients treated with high-dose induction had higher early virological response rates ( 63 % vs. 39 % , P<0.05 ) . This initial positive effect was lost during the last 24 weeks of treatment yielding sustained virological response ( SVR ) rates of 26 % in both groups . Relapse patients revealed SVR in 70 % and 38 % in groups A and B ( NS ) . Treatment was well tolerated with side effect-related preterm discontinuations in 8 % and 5 % . CONCLUSIONS CIFN and ribavirin treatment induced considerable SVR rates in patients with non-response or relapse to IFNalpha+/-ribavirin . Viral elimination rates might be further increased by continuous daily administration of CIFN and weight-adjusted ribavirin dosing In previous studies employing interferons ( IFNs ) in the treatment of chronic hepatitis C , there have been few reliable predictors of sustained responses . We retrospectively evaluated the predictive value of hepatitis C virus (HCV)-RNA measurements in the first few months during consensus interferon ( CIFN ) treatment using a sensitive reverse-transcriptase polymerase chain reaction assay to determine sustained responses . Data from two large treatment trials , one of IFN-naive patients and one of retreated relapsers and nonresponders , were used , including serum sample s at 2-week intervals in the naive study and 8-week intervals in the retreatment study . Patients received initial CIFN ( 9 microgram ) treatment for 6 months and were assessed 6 months after treatment . There were 28 sustained viral responders of 232 CIFN-treated patients . Of the sustained responders , 48 % had already cleared HCV RNA from serum ( < 100 copies/mL ) by week 2 , 78 % by week 4 , 81 % by week 6 , and 96 % by week 12 . Patients with early HCV-RNA clearance were more likely to have sustained responses than those who responded later . Early clearance of HCV from serum was also associated with greater likelihood of a sustained response to 48 weeks of retreatment with 15 microgram CIFN . Ninety-five percent of the sustained responders were HCV-RNA-negative by week 8 of retreatment . Early assessment of HCV RNA may help in the prediction of sustained responses to IFN and allow the value of continued treatment to be determined early in the course of IFN therapy AIM To assess the efficacy of different schedules of consensus interferon ( CIFN ) plus ribavirin in retreating chronic hepatitis C patients who relapsed after recombinant interferon ( rIFN ) monotherapy . METHODS Forty-five patients ( 34 males and 11 females ) with chronic hepatitis due to hepatitis C virus ( HCV ) genotype 1 who relapsed after a previous course of rIFN monotherapy were r and omized to receive 9 mug CIFN three times per week for 52 wk ( group A , n = 22 ) or 18 mug CIFN three times per week for 52 wk ( group B , n = 23 ) in combination with ribavirin 800 to 1200 mg daily for 52 wk ( according to body weight ) . Virological response was evaluated at week 24 ( EVR ) , at the end of treatment ( ETR ) and at 76 wk ( SVR ) . RESULTS By intention-to-treat analysis , subjects in group A had an EVR in 35 % of cases , an ETR in 35 % and a SVR in 27.3 % of cases . Subjects in group B had an EVR in 32 % of cases , an ETR in 35 % and a SVR in 26.1 % of cases . Treatment was stopped because of adverse effects ( mostly intolerance ) in 15 patients ( 6 in group A and 9 in group B ) . IFN dose reduction was needed in 2 patients ( 1 in group A and 1 in group B ) . Ribavirin dose was reduced in 2 patients in group A and 1 in group B respectively . Among the 15 subjects who received at least 80 % of the intended schedule , the rate of SVR was 80 % ( 6 in group A and 6 in group B ) . CONCLUSION CIFN in combination with ribavirin when given to HCV genotype 1 relapsers after rIFN monotherapy obtains an unsatisfactory rate of sustained viral clearance independently of dosage of the drug . This may be due to its scarce tolerability UNLABELLED Fibrosis progression in chronic liver disease has usually been evaluated by liver biopsy using insensitive semiquantitative numerical scores . An alternative to this is to measure fibrous tissue quantitatively using morphometric image analysis . The aim of this study was to quantify fibrosis progression in a cohort of patients with treatment-refractory chronic hepatitis C enrolled in a placebo-controlled clinical trial of interferon gamma-1b ( IFN-gamma 1b ) for the treatment of advanced hepatic fibrosis . We used morphometry to quantify the amount of fibrous tissue in liver biopsies performed at baseline and after 48 weeks in 245 patients who had paired unfragmented , adequate-sized specimens and correlated the results with clinical and laboratory parameters . Eighty-seven patients were treated with placebo and 158 with IFN-gamma 1b . No effect of the drug on fibrosis was found in the trial , and so data from all 245 patients were combined for analysis . At baseline , 78 % had cirrhosis ; 22 % , bridging fibrosis . The mean morphometrically determined collagen content increased by 58 % between baseline and 48 weeks . There were statistically significant but weak correlations of fibrosis with platelet count , albumin , bilirubin , INR , and hyaluronic acid ; however , changes in these did not correlate with or predict changes in fibrosis in the liver biopsy . CONCLUSION In advanced chronic hepatitis C , fibrosis increases at a rapid pace that can only be detected by morphometry . This technique can be used in future therapeutic trials of agents to inhibit fibrosis progression Approximately half of all patients with chronic hepatitis C show an initial biochemical response to interferon , but only 15 % to 20 % of patients achieve a sustained response . We studied the efficacy of retreatment with interferon for patients with chronic hepatitis C who showed transient biochemical responses to initial treatment . Thirty patients who relapsed were retreated 1 to 52 months ( median 14 ) after the end of initial treatment , according to the previously used regimens . The responses were correlated with the pre-retreatment patient data . The liver histologic grade s , compared with those found before the initial treatment , were better in eight ( 27 % ) patients but worse in six ( 20 % ) , whereas the fibrosis stage was improved in five ( 17 % ) but worsened in eight ( 27 % ) . All patients displayed end-of-retreatment biochemical responses . Of the 30 patients , 10 ( 33 % ) achieved sustained aminotransferase normalization and serum hepatitis C virus ( HCV ) RNA clearance , but the remaining 20 patients showed relapse within 1 year after cessation of retreatment . Univariate analysis associated the sustained response with low pre-retreatment viral loads ( 0.8 ± 0.7 MEq/mL vs. 9.1 ± 6.5 MEq/mL;p = 0.006 ) , short treatment intervals ( 13 ± 13 months vs. 22 ± 14 months;p = 0.031 ) , and low histologic grade s ( 1.3 ± 0.7 vs. 1.9 ± 0.7;p = 0.039 ) . However , multivariate analysis indicated that only the pre-retreatment viral load was predictive of the sustained response ( p = 0.049 ) . These findings suggest that transient responders to interferon are likely to respond to retreatment but the achievement of a sustained response depends on the HCV viral load before retreatment From August 1978 until March 1979 , 14 batches of anti-D immune globulin contaminated with hepatitis C virus ( HCV ) genotype 1b ( 20 , 000 - 480,000 copies/dose ) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany . All 2,867 women involved had been recalled after January 12 , 1979 for repeated screening of alanine transaminase ( ALT ) . They were prospect ively followed in regional centers . We have reexamined a cohort of 1,018 women ( median age 24 , range 16 - 38 years at infection ) on follow-up for 20 years in 9 representative centers . Within 6 months after anti-D administration , 10 % of these women had no evidence of disease and 90 % had acute hepatitis C ( n = 917 ) including 49 % with symptomatic and 22 % with icteric course . After 20 years , 85 % of the 917 affected women still tested positive for HCV antibodies ( among them 3 % responded to interferon treatment ) and 55 % were positive for HCV RNA ( among them 7 % were nonresponders to interferon and 3 % were apparent HCV carriers ) . Only 4 ( 0.4 % ) had overt cirrhosis . Two ( 0.2 % ) died of superinfected fulminant hepatitis B or alcoholism and cirrhosis , respectively . Histology obtained in 44 % of the viremic women showed hepatitis of minimal to moderate grade in 96 % , portal fibrosis in 47 % , and septal fibrosis in 3 % of the cases . In conclusion , formerly healthy young women , without hepatic comorbidity , may clear HCV ( 1b ) infection in half of the cases or develop mild chronic hepatitis C with low risk of progression to cirrhosis within 20 years AIM To assess the efficacy of triple therapy ( peginte-rferon or high dose st and ard interferon , plus ribavirin and amantadine ) in nonresponders to prior combination therapy . METHODS A total of 196 patients were enrolled in a multicenter , open , r and omized study . Patients were given 180 mug/wk of peginterferon-alpha-2a ( 40 kDa ) plus ribavirin ( 800 - 1000 mg/d ) and amantadine ( 200 mg/d ) for 48 wk ( group A ) or interferon-alpha-2a ( 6 MU/d for 4 wk , 3 MU/d for 20 wk , and 3 MU tiw for 24 wk ) plus ribavirin ( 800 - 1000 mg/d ) and amantadine ( 200 mg/d ) for 48 wk ( group B ) . RESULTS Overall sustained virologic response ( SVR ) was 26.6 % ( 32.1 % and 19.5 % in group A and B , P = 0.057 ) . Baseline ALT > 120 UI/L ( OR 2.4 ; 95 % CI : 1.11 to 5.20 ; P = 0.026 ) and HCV RNA negativity after 12 wk ( OR 8.7 ; 95 % CI : 3.87 to 19.74 ; P < 0.0001 ) were independently associated with SVR . Therapy discontinuation occurred less frequently in patients treated with peginterferon than st and ard interferon ( P = 0.036 ) . CONCLUSION More than 25 % of nonresponders to combination therapy can eradicate HCV infection when retreated with triple therapy , especially if they have a high baseline ALT and are treated with pegylated interferon Long‐term follow up studies of hepatitis C virus ( HCV ) infection rarely exceed 20–25 yr . We studied the outcome of HCV infection in 35‐yr‐old adults infected at birth ( 1968 ) through mini transfusions of blood . A retrospective‐ prospect i ve study was carried out . The cohort included 31 individuals who were given mini blood transfusions ( 21–30 ml ) collected from a donor subsequently revealed to be HCV infected . At enrollment ( 1998 ) , 18 of 31 ( 58.1 % ) recipients had anti‐HCV antibody and 16 ( 88.9 % ) of them were HCV‐RNA positive . All viremic recipients and the infectious donor had the same genotype 1b . Sequence analysis of E1/E2 and NS5b regions , coupled with phylogenetic analysis , indicated that HCV isolates from donor/recipients were linked . Eleven of the 16 viremic recipients gave consent to liver biopsy . Nine had no fibrosis or mild portal fibrosis and 2 had either discrete ( Ishak 's staging 3 ) or marked ( Ishak 's staging 4 ) fibrosis . During the prospect i ve follow‐up period ( 1998–2003 ) , 2 patients were given therapy , one of whom achieved sustained clinical and virologic response . A second biopsy , performed in 5 patients at a 5 yr interval , revealed no substantial modifications in 4 cases and progression from absence of fibrosis to mild portal fibrosis in the fifth . In conclusion , taking into account the limited study sample , these findings suggest that HCV infection acquired early in life shows a slow progression and mild outcome during the first 35 yr of infection . ( HEPATOLOGY 2004;39:90–96 . BACKGROUND / AIMS Retreatment of relapses of chronic hepatitis C with a st and ard regimen of interferon plus ribavirin for 6 months obtains a sustained response in a minority of patients with high viraemia and genotype 1b . We aim ed to assess whether increasing the interferon dose and prolonging the time of combined treatment may enhance the effectiveness , and also to evaluate the tolerability , and to identify the determinants of sustained response . METHODS Fifty subjects with chronic hepatitis C who had relapsed after one or more courses of a-interferon monotherapy were r and omised to receive alpha2b interferon ( 6 MU tiw ) plus ribavirin ( 1000 - 1200 mg daily ) for 6 or 12 months . ALT normalisation and serum HCV-RNA clearance at the end of treatment and 6 months after stopping therapy were used as markers for sustained response . RESULTS End-of-treatment response was achieved in 48 patients ( 96 % ) and 27 ( 54 % ) had a complete sustained response . Patients treated for 12 months had a higher rate of sustained response ( 18/25 , 72 % ; 95 % C.I. 0.54 - 0.89 ) than those treated for 6 months ( 9/25 , 36 % ; 95 % C.I. 0.17 - 0.55 , p=0.01 ) . Twelve months of therapy was significantly more effective for patients with genotype 1b and baseline serum HCV-RNA greater than 450 000 copies/ml ( p=0.005 ) . Seven subjects ( 14 % ) discontinued treatment because of side effects . Logistic regression analysis showed 12 months of therapy , young age and low pre-treatment serum HCV-RNA to be independent predictors of sustained response . CONCLUSIONS Relapsers with genotype 1b and high levels of HCV-RNA will benefit from a 12-month course of 6 MU tiw interferon plus ribavirin , while subjects with genotype 1b and low levels of serum HCV-RNA or with genotype other than 1b may be treated for 6 months BACKGROUND & AIMS Several studies have reported that low doses of interferon can delay the development of hepatocellular carcinoma ( HCC ) and progression of chronic hepatitis C. We investigated the incidence of clinical events among participants of the Evaluation of PegIntron in Control of Hepatitis C Cirrhosis (EPIC)3 program . METHODS Data were analyzed from an open-label r and omized study of patients with chronic hepatitis C who had failed to respond to interferon alfa plus ribavirin . All patients had compensated cirrhosis with no evidence of HCC . Patients received peginterferon alfa-2b ( 0.5 μg/kg/week ; n=311 ) or no treatment ( controls , n=315 ) for a maximum period of 5 years or until 98 patients had a clinical event ( hepatic decompensation , HCC , death , or liver transplantation ) . The primary measure of efficacy was time until the first clinical event . RESULTS There was no significant difference in time to first clinical event among patients who received peginterferon alfa-2b compared with controls ( hazard ratio [ HR ] , 1.452 ; 95 % confidence interval [ CI ] : 0.880 - 2.396 ) . There was no decrease in the development of HCC with therapy . The time to disease progression ( clinical events or new or enlarged varices ) was significantly longer for patients who received peginterferon alfa-2b compared with controls ( HR , 1.564 ; 95 % CI : 1.130 - 2.166 ) . In a prospect ively defined sub analysis of patients with baseline portal hypertension , peginterferon alfa-2b significantly increased the time to first clinical event compared with controls ( P=.016 ) . There were no new safety observations . CONCLUSIONS Maintenance therapy with peginterferon alfa-2b is not warranted in all patients and does not prevent HCC . However , there is a potential clinical benefit of long-term suppressive therapy in patients with preexisting portal hypertension summary . Retreatment of relapser patients with chronic hepatitis C with the st and ard dose of interferon ( IFN ) of 3 million units ( MU ) thrice weekly ( tiw ) plus ribavirin for 24 weeks achieves a sustained response in 30 and 73 % of patients with genotype 1 and 2 or 3 , respectively . The aim of this study was to evaluate the efficacy and safety of IFN alpha-2b induction therapy , followed by prolonged treatment with a high dose of IFN alpha-2b plus ribavirin in relapser patients . A total of 119 patients were r and omized to receive IFN alpha-2b 5 MU daily ( Group A : 59 patients ) or IFN alpha-2b 5 MU tiw ( Group B : 60 patients ) for 4 weeks followed by IFN ( 5 MU tiw ) and ribavirin ( 1000 - 1200 mg/day ) for 48 weeks in both groups . The primary end point was hepatitis C virus (HCV)-RNA clearance at week 24 after the end of treatment . A sustained virological response ( SVR ) was achieved in 68 and 60 % of Group A and B patients , respectively ( P = 0.37 ) . Logistic regression analysis identified genotype 2 or 3 as the only independent factor associated with response , whereas induction regimen and baseline viraemia levels did not affect the response . The overall SVR was 53 and 72 % in patients with genotype 1 or 4 and 2 or 3 , respectively . In conclusion , induction IFN therapy does not enhance the SVR to a 48-week combination therapy . Our study suggests that relapsed patients with genotype 1 or 4 may achieve significant response rates of approximately 50 % , if retreated with 5 MU tiw IFN plus ribavirin for 48 weeks BACKGROUND Peginterferon-ribavirin therapy is the current st and ard of care for chronic infection with hepatitis C virus ( HCV ) . The rate of sustained virologic response has been below 50 % in cases of HCV genotype 1 infection . Boceprevir , a potent oral HCV-protease inhibitor , has been evaluated as an additional treatment in phase 1 and phase 2 studies . METHODS We conducted a double-blind study in which previously untreated adults with HCV genotype 1 infection were r and omly assigned to one of three groups . In all three groups , peginterferon alfa-2b and ribavirin were administered for 4 weeks ( the lead-in period ) . Subsequently , group 1 ( the control group ) received placebo plus peginterferon-ribavirin for 44 weeks ; group 2 received boceprevir plus peginterferon-ribavirin for 24 weeks , and those with a detectable HCV RNA level between weeks 8 and 24 received placebo plus peginterferon-ribavirin for an additional 20 weeks ; and group 3 received boceprevir plus peginterferon-ribavirin for 44 weeks . Nonblack patients and black patients were enrolled and analyzed separately . RESULTS A total of 938 nonblack and 159 black patients were treated . In the nonblack cohort , a sustained virologic response was achieved in 125 of the 311 patients ( 40 % ) in group 1 , in 211 of the 316 patients ( 67 % ) in group 2 ( P<0.001 ) , and in 213 of the 311 patients ( 68 % ) in group 3 ( P<0.001 ) . In the black cohort , a sustained virologic response was achieved in 12 of the 52 patients ( 23 % ) in group 1 , in 22 of the 52 patients ( 42 % ) in group 2 ( P=0.04 ) , and in 29 of the 55 patients ( 53 % ) in group 3 ( P=0.004 ) . In group 2 , a total of 44 % of patients received peginterferon-ribavirin for 28 weeks . Anemia led to dose reductions in 13 % of controls and 21 % of boceprevir recipients , with discontinuations in 1 % and 2 % , respectively . CONCLUSIONS The addition of boceprevir to st and ard therapy with peginterferon-ribavirin , as compared with st and ard therapy alone , significantly increased the rates of sustained virologic response in previously untreated adults with chronic HCV genotype 1 infection . The rates were similar with 24 weeks and 44 weeks of boceprevir . ( Funded by Schering-Plough [ now Merck ] ; SPRINT-2 Clinical Trials.gov number , NCT00705432 . ) BACKGROUND / AIMS Only a small fraction of patients with chronic hepatitis C have a sustained biochemical or virologic response to a st and ard course of alpha-interferon therapy . Thus , alternative treatments are needed particularly for non-responders . The main objective of this study was to evaluate the efficacy of alpha-interferon in combination with ribavirin in patients who had not responded to a previous course of alpha-interferon . METHODOLOGY In this prospect i ve open trial , 26 patients who had not responded to a previous course of interferon monotherapy , were treated for 6 months with a combination of alpha-interferon 2b , 5 MU thrice weekly , plus ribavirin 1000 or 1200 mg daily . They were followed-up for at least 6 months after therapy . RESULTS At the end of treatment , 3 patients ( 12 % ) had normal aminotransferase levels and two ( 8 % ) tested negative for HCV-RNA in serum . After 6 months of follow-up , all patients had HCV viremia and only one ( 3.8 % ) was still in biochemical remission . One patient dropped out because of side effects and another was lost during follow-up . CONCLUSIONS alpha-interferon-ribavirin combination is ineffective in treating patients who had had no response to interferon monotherapy Background : In patients with hepatitis C virus (HCV)-genotype 1b and a high virus load , of more than 1 Meq/ml by the DNA probe assay , the clearance of HCV-RNA was achieved in only 10 % with a 6-month interferon ( IFN ) course . We therefore assessed the efficacy of prolonged IFN therapy in patients with HCV-genotype 1b and a high virus load . Methods : A total of 51 patients with HCV genotype 1b who were given 6 million units ( MU ) of natural IFN-α daily for 8 weeks followed by three-times-weekly treatment with natural IFN-α for 16 weeks , were enrolled in this trial . These 51 patients were r and omly assigned to one of two schedule groups at the time of termination of the first IFN therapy . The 48-week-group patients ( n = 25 ) were given 6 MU of natural IFN-α by intramuscular injection three times weekly for 24 weeks , beginning within a week after the termination of the first IFN therapy . The 72-week-group patients ( n = 26 ) were given 6 MU of IFN-α by intramuscular injection three times a week for 48 weeks , beginning within a week after the termination of the first IFN therapy . The therapeutic efficacy was evaluated 24 and 30 months after the initiation of the first IFN treatment . A virological response ( VR ) to IFN therapy was defined as the normalization of serum alanime amino transferase ( ALT ) level ( ALT ≲ 50 IU ) and HCV-RNA negativity at the two time points . Biochemical response ( BR ) was defined as the normalization of serum ALT , but positivity for HCV-RNA , assessed by commercial Amplicor HCV qualitative assays , at the two time points . Results : The efficacy of IFN treatment was assessed in relation to the IFN administration schedule by intention-to-treat ( ITT ) analysis and per- protocol analysis . With respect to the IFN regimen , VR occurred in 16.6 % ( 4/24 ) of the patients in the 48-week-group with additional IFN and in 20 % ( 5/25 ) in the 72-week-group with additional IFN by ITT analysis . The BR rate was 33.3 % ( 8/24 ) in the 48-week group and 48 % ( 12/25 ) in the 72-week group . Conclusions : We found that prolonged IFN therapy could be a worthwhile treatment strategy for patients with HCV genotype 1b and a high serum virus load To examine the effects of interferon ( IFN ) therapy on clinical , biochemical , and histological features in patients with compensated hepatitis C virus (HCV)-related cirrhosis , we have conducted a r and omized , controlled trial of IFN therapy versus observation . Eight centers included a total of 99 patients with biopsy-proven cirrhosis . IFN-alpha2b , 3 million units three times per week , or no antiviral therapy was given for 48 weeks . Twenty-three patients dropped out . End-of-treatment biochemical response was not observed in any of the 39 controls but was observed in 6 of the 47 treated patients ( P < .02 ) ; sustained biochemical response was obtained in only 2 treated patients . Controls and treated patients did not significantly differ with regard to the changes in serum level of albumin , bilirubin , alpha-fetoprotein , in plasma prothrombin , in histological activity , or liver collagen content . During trial or follow-up ( 160 + /- 57 weeks ) , hepatocellular carcinoma developed in 9 controls and 5 treated patients ( NS ) ; decompensation of cirrhosis occurred in 5 controls and 7 treated patients . Seven controls and 10 treated patients died . In conclusion , in patients with compensated HCV-related cirrhosis , a 48-week course of IFN therapy is safe and is able to induce end-of-treatment biochemical response in a significant proportion of patients . However , a 48-week course of IFN therapy usually fails to achieve sustained response and , within the limit of this study , did not significantly improve the 3-year outcome . Therefore , a longer course of IFN therapy or combination therapy with ribavirin should be evaluated in patients with HCV-related cirrhosis Context Some patients with chronic hepatitis C virus infection do not respond to initial treatment with pegylated interferon plus ribavirin . Contribution This r and omized trial compared peginterferon-2a plus ribavirin for either 48 or 72 weeks in adults with hepatitis C who had not responded to peginterferon-2b plus ribavirin . Re-treating the nonresponders for 72 weeks increased sustained virologic response rates more than did re-treatment for 48 weeks ( 16 % vs. 8 % ) . Implication Re-treating nonresponders for a longer duration improved response rates , although the rates remained disappointingly low in these patients . The Editors The st and ard of care for patients with chronic hepatitis C is treatment with pegylated interferon plus ribavirin ( 1 , 2 ) . Despite the increasing efficacy of therapy , approximately 50 % of patients with hepatitis C virus ( HCV ) genotype 1 infection and 20 % to 30 % of patients with HCV genotype 2 or 3 infection do not achieve a sustained virologic response ( SVR ) after a first course of therapy ( 3 ) , which adds to the large and growing pool of patients who have not responded to treatment with the st and ard of care and are therefore difficult to treat . These persons are at risk for cirrhosis , liver failure , and hepatocellular carcinoma ( 4 ) . Sustained virologic response to interferon-based treatment is associated with eradication of HCV infection and histologic improvement in liver disease ( 5 ) . Data suggest that re-treatment of patients with pegylated interferon plus ribavirin can eradicate HCV infection in patients who have not responded to a first course of conventional interferon-based therapy ( 6 , 7 ) , but few data exist on the efficacy of re-treatment in patients who have not responded to pegylated interferon plus ribavirin ( 8) . Intensification of therapy by increasing the dose of interferon or ribavirin or extending the duration of treatment has been shown to enhance efficacy , not only in treatment-naive persons ( 9 , 10 ) but also in nonresponders to conventional interferon plus ribavirin ( 11 , 12 ) . Current guidelines ( 13 ) advise against re-treatment with pegylated interferon and ribavirin . We recruited patients who had not responded to previous treatment with peginterferon-2b plus ribavirin to evaluate the efficacy of a 12-week , fixed-dose induction regimen of peginterferon-2a plus st and ard-dose ribavirin and extended treatment with st and ard doses of both drugs . Methods Design Figure 1 shows an overview of the study design . Investigators conducted the study at 106 centers in North America , Europe , and Brazil . Patients were recruited between September 2003 and April 2005 , and the last patient completed follow-up in February 2007 . We r and omly assigned 950 participants to treatment , and 942 received at least 1 dose of a study drug . Figure 1 . Study design . * Only in groups B and D. Only in groups A and C. Eligible patients received treatment with subcutaneous peginterferon-2a ( Pegasys , Roche , Basel , Switzerl and ) plus a st and ard dose of oral ribavirin ( 1000 mg/d for patients weighing < 75 kg and 1200 mg/d for those weighing 75 kg ) ( Copegus , Roche ) . The institutional review boards of each participating center approved the protocol , and all patients provided written informed consent . We conducted this study according to the guidelines of the Declaration of Helsinki and under the provisions of good clinical practice . Setting and Participants We conducted this study in specialist outpatient hepatology clinics . We used no specific methods to recruit patients to the study . Investigators recruited patients from existing patient rolls or through routine referrals from colleagues . Eligible patients were adults age 18 years or older with serologic evidence of chronic hepatitis C ; quantifiable serum HCV RNA levels ( > 600 IU/mL ) , as measured by using the Cobas Amplicor HCV Monitor Test , version 2.0 ( Roche Diagnostics , Basel , Switzerl and ) ; and histologic findings on a liver biopsy specimen consistent with the diagnosis of chronic hepatitis C. Patients with hepatic cirrhosis were eligible if they had compensated liver disease ( 14 ) . We had well-defined criteria for previous nonresponse : eligible patients who had received at least 12 weeks of combination therapy with peginterferon-2b ( 1.0 g/kg per week ) plus ribavirin ( 800 mg/d ) and had detectable serum HCV RNA at every postbaseline assessment , at least 1 of which was performed after week 12 . Treatment must have been discontinued at least 12 weeks before enrollment . Patients were ineligible if they had discontinued treatment with peginterferon-2b plus ribavirin because of hematologic adverse events or had received drugs for HCV infection or immunomodulatory agents within 6 months of enrollment . Patients who were co-infected with hepatitis A or B virus or HIV were also excluded , as were those with a history of chronic liver disease not attributed to chronic hepatitis C , a neutrophil count less than 1.5109 cells/L , platelet count less than 90109 cells/L , or a hemoglobin concentration less than 120 g/L in women or less than 130 g/L in men . Appendix Table 1 lists all inclusion and exclusion criteria used to recruit patients . Appendix Table 1 . Inclusion and Exclusion Criteria R and om Assignment and Interventions We r and omly assigned patients to 1 of 4 open-label treatment groups at baseline in a 2:1:1:2 ratio ( Figure 2 ) . We selected this ratio to optimize the power of the primary comparison and thus maximize the number of patients assigned to groups included in the primary comparison of treatment outcomes . Figure 2 . Study flow diagram . AE = adverse event . The 4 treatment groups were as follows : peginterferon-2a ( 360 g/wk ) plus ribavirin for 12 weeks , then peginterferon-2a ( 180 g/wk ) plus ribavirin to complete 72 weeks of treatment ( group A ) ; peginterferon-2a ( 360 g/wk ) plus ribavirin for 12 weeks , then peginterferon-2a ( 180 g/wk ) plus ribavirin to complete 48 weeks of treatment ( group B ) ; peginterferon-2a ( 180 g/wk ) plus ribavirin for 72 weeks ( group C ) ; or peginterferon-2a ( 180 g/wk , ) plus ribavirin for 48 weeks ( group D ) . Patients were r and omly assigned in permuted blocks of 12 , stratified by geographic region , HCV genotype ( genotype 1 vs. nongenotype 1 ) , and histologic diagnosis ( cirrhosis or transition to cirrhosis vs. no cirrhosis or transition to cirrhosis ) . The computerized r and omization list was generated by the sponsor and incorporated into a central interactive voice-response system managed by S-Clinica ( Brussels , Belgium ) . At the baseline visit , the investigator called the interactive voice-response system to obtain information about a patient 's assignment to a treatment group , which was confirmed by fax to the study site within 1 hour . We used stratified r and om assignment to balance the distribution of regions , genotypes , and histologic diagnoses among the treatment groups . We permitted but did not encourage the use of erythropoietin-stimulating agents and granulocyte colony-stimulating factor . In the event of an adverse reaction or laboratory abnormality , we decreased the dose of peginterferon-2a in steps from 360 g/wk to 180 , 135 , and 90 g/wk for patients in groups A and B and from 180 g/wk to 135 , 90 , and 45 g/wk for patients in groups C and D. We decreased the dose of ribavirin to 600 mg/d in patients whose hemoglobin level decreased to less than 100 g/L but remained at least 85 g/L or , in patients with clinical ly significant cardiovascular disease , in the event of a 20-g/L or greater decrease in hemoglobin during any 4-week interval . Ribavirin therapy was to be discontinued if the hemoglobin concentration decreased to less than 85 g/L , or if it remained less than 120 g/L despite 4 weeks of treatment at a reduced dose in patients with clinical ly significant cardiovascular disease . On resolution of the precipitating event , the investigator could adjust the dosage of either study drug upward at his or her discretion . Outcomes and Follow-up We determined serum HCV RNA level by quantitative ( Cobas Amplicor HCV Monitor Test , version 2.0 ) and qualitative ( Cobas Amplicor HCV Test , version 2.0 ; limit of detection , 50 IU/mL ) assays at baseline and at weeks 12 , 24 , and 48 during treatment in all patients ; at week 72 of treatment in patients r and omly assigned to 72 weeks of treatment ( groups A and C ) ; and after 12 and 24 weeks of untreated follow-up . Discontinuation of treatment was allowed in patients with detectable HCV RNA at or after week 24 . Virologic end points were early virologic response at week 12 , defined as nondetectable HCV RNA ( < 50 IU/mL , qualitative assay ) in serum or a 2-log10 decrease or greater in serum HCV RNA by quantitative assay , and SVR , defined as nondetectable HCV RNA ( < 50 IU/mL ) in serum at the end of the 24-week untreated follow-up period ( week 96 for patients in groups A and C and week 72 for patients in groups B and D ) . The primary efficacy end point in the trial was SVR at the end of follow-up . The primary comparison was between patients treated with fixed-dose induction plus extended- duration combination therapy ( group A ) and those treated with the st and ard regimen ( group D ) . Study monitors verified and cross-checked study case report forms against investigators ' records . In addition , study sites , a central laboratory , and a contract research organization were audited as part of the clinical quality assurance program . Assessment of Adverse Events At each scheduled visit ( Figure 1 ) , we assessed adverse events by physical examination , laboratory tests , and adverse event reports . Investigators elicited information from patients regarding adverse events that occurred since the last visit by asking open-ended questions . Information collected for each adverse event included a description of the event , date of onset , duration , intensity , relationship to study drugs , required treatment , dosage adjustments to study treatment , and outcome . Statistical Analysis We estimated that a total of 592 patients would be required to detect a 10 % difference BACKGROUND / AIMS Initial high-dose interferon-alpha induction therapy in combination with ribavirin improves sustained response rates in treatment-naïve patients . This prospect i ve , r and omized , controlled study tested whether non-responders or relapsers to interferon monotherapy also benefit from induction therapy . METHODS Patients with chronic hepatitis C who had not responded to ( n=75 ) or relapsed ( n=80 ) after previous interferon therapy were r and omized to receive three different interferon doses during the first 14 weeks of therapy ( A : 10 MU IntronA/day for 2 weeks , followed by 10 MU/2 days for 12 weeks ; B:5 MU/d for 14 weeks ; C : 5 MU/2 days for 14 weeks ) followed in all by 5 MU/2 days for 24 weeks . All patients received 1 - 1.2 g ribavirin/day throughout the whole study . RESULTS The rates of viral clearance at any time on treatment were similar in all groups . Sustained response rates were also not different among the groups in interferon nonresponders ( A 32 % , B 29 % , C 31 % ) and relapsers ( A 64 % , B 68 % , C 71 % ) , respectively , as well as in patients with different genotypes . As expected , sustained response rates were higher in patients with genotype non-1 than in those with genotype 1 . CONCLUSION High-dose induction therapy does not improve the outcome of interferon/ribavirin therapy in interferon nonresponders or relapsers Chronic hepatitis C ( non-A , non-B hepatitis ) is a common and often progressive viral liver disease . To assess the efficacy of therapy with the antiviral agent interferon alfa , we r and omly assigned 166 patients with chronic hepatitis C to treatment with either 3 million or 1 million units of recombinant interferon alfa three times weekly for 24 weeks , or to no treatment . The probability of normalization or near normalization of the serum alanine aminotransferase levels after six months of interferon therapy was 46 percent in patients treated with 3 million units of interferon ( P less than 0.001 ) and 28 percent in those treated with 1 million units ( P less than 0.02 ) , but only 8 percent in untreated patients . The serum alanine aminotransferase level became completely normal in 22 of the 26 patients ( 85 percent ) who responded to treatment with 3 million units of interferon and 9 of the 16 patients ( 56 percent ) who responded to treatment with 1 million units . The patients who received 3 million units of interferon had histologic improvement because of the regression of lobular and periportal inflammation . Relapse within six months after the completion of treatment occurred in 51 percent of the patients treated with 3 million units of interferon and 44 percent of those treated with 1 million units . We conclude that a 24-week course of interferon therapy is effective in controlling disease activity in many patients with hepatitis C , although relapse after the cessation of treatment is common This international , r and omized , active‐controlled , parallel‐group , double‐blind dose‐finding study compared peginterferon alfa‐2b ( PegIntron ™ ) to interferon alfa‐2b for the initial treatment of compensated chronic hepatitis C. We r and omly assigned 1,219 subjects to receive either the st and ard three‐times‐weekly ( TIW ) interferon alfa‐2b dose ( 3 MIU ) or the once‐weekly ( QW ) peginterferon alfa‐2b ( 0.5 , 1.0 , or 1.5 μg/kg ) . Subjects were treated for 48 weeks and then followed for an additional 24 weeks . All 3 peginterferon alfa‐2b doses significantly ( P ≤ .042 ) improved virologic response rates ( loss of detectable serum HCV RNA ) after treatment and after follow‐up , as compared with interferon alfa‐2b . Unlike the end‐of‐treatment virologic response , the sustained virologic response rate was not dose‐related above 1.0 μg/kg peginterferon alfa‐2b because of a higher relapse rate among patients treated with 1.5 μg/kg peginterferon alfa‐2b , particularly among patients infected with genotype 1 . All 3 peginterferon alfa‐2b doses decreased liver inflammation to a greater extent than did interferon alfa‐2b , particularly in subjects with sustained responses . No new adverse events were reported , and the majority of adverse events and changes in laboratory values were mild or moderate . In conclusion , peginterferon alfa‐2b maintained ( 0.5 μg/kg ) or surpassed ( 1.0 , 1.5 μg/kg ) the clinical efficacy of interferon alfa‐2b while preserving its safety profile . The higher rate of virologic response during treatment with 1.5 μg/kg peginterferon alfa‐2b in patients infected with genotype 1 and high viral levels warrants further evaluation We studied the efficacy of three interferon alfa‐2b ( IFN‐α2b ) regimens for the retreatment of patients with chronic hepatitis C ( CHC ) with prior complete response followed by relapse . Consecutive patients with CHC who had a complete biochemical response but relapse after a first course of 6 months of IFN with 3 million units ( MU ) given subcutaneously three times per week were enrolled in the study . Six to 24 months after the end of the first treatment , the patients were r and omly assigned to receive IFN with either the same regimen ( group 1 ) , a regimen of 12 months with 3 MU ( group 2 ) , or a regimen of 6 months with 10 MU ( group 3 ) . Sustained biochemical response was defined as normal serum alanine transaminase ( ALT ) values during the follow‐up and sustained virological response as a clearance of hepatitis C virus ( HCV ) RNA from the serum at the end of follow‐up ( 6 months ' posttreatment ) . Histological improvement was defined as a decrease of 1 point in Metavir score between the first liver biopsy and a biopsy performed at 6 months ' postretreatment . Two hundred forty‐seven patients were r and omized : 75 to group 1 , 91 to group 2 , and 81 to group 3 . In an intent‐to‐treat analysis , 12 % , 36.3 % , and 18.5 % of patients had a sustained biochemical response after retreatment in groups 1 , 2 , and 3 , respectively ( P < .001 ) ; 13.8 % , 32.4 % , and 17.2 % of patients had a sustained virological response after retreatment in groups 1 , 2 , and 3 , respectively ( P < .05 ) . A low viral load and patients in group 2 were independently associated with a sustained biochemical response . A low Knodell score index before treatment , patients with a high level of ALT before retreatment , genotype 3 , low viral load , and patients in group 2 were independently associated with sustained virological response . Younger age , a high level of ALT , a low level of γ‐glutamyl transferase before retreatment , low viral load , and patients in group 2 were independently associated with sustained biochemical and virological response . Among the 80 patients with repeated liver biopsies , 47.6 % had improved histological activity scores ; this improvement was associated with a sustained biochemical and virological response . In patients with CHC initially treated with 3 MU of IFN given subcutaneously three times per week over a 6‐month period , and who subsequently developed a relapse after a biochemical response , retreatment with a regimen of 3 MU of IFN given three times per week for 12 months produced better biochemical and virological sustained response rates than regimens involving a higher dose or a shorter duration of retreatment . The biochemical and virological sustained response was associated with histological improvement BACKGROUND / AIMS To analyze the kinetics of the hepatitis C virus and the patterns of resistance to interferon alpha , we assessed HCV RNA levels early during retreatment with high-dose interferon in patients who did not respond to st and ard treatment . METHODS Eleven non-responders to previous therapy with 3 - 6 MU interferon three times a week were retreated with daily 10 MU . Plasma was sample d at days 0 , 1 , 2 , 3 , 14 and 28 ; all sample s were prepared within 2 h and stored at -70 degrees C without thawing until analysis . The quantitative HCV RNA level was assessed by the Superquant assay ( NGI , USA ) . The Eurohep reference panel , tested blindly , confirmed the linearity of the assay with a detection limit for genotypes 1 and 3 between 10(2 ) and 10(3 ) copies/ml . RESULTS All patients showed a fall in viral load between week 0 and week 2 ( 2.6 log , i.e. 99.7 % , range 1.3 - 4.7 log ) , whereas no fall was detected after week 2 . Closer examination in nine patients revealed that all had a dramatic fall in the first 2 days ( first day 1.8 log , 0.8 - 3.5 ; second day 0.8 log , -0.2 - 1.3 ) , without any significant fall thereafter . The calculated half-life of viral decay in plasma was 5 ( 2 - 8.9 ) h , corresponding to a clearance of 2.4 ( 0.2 - 13.7 ) x 10(11 ) virions per day . Sustained responders showed a significantly greater fall in viral load in the first day ( 3.2 log , 2.8 - 3.5 ) than those who did not respond ( 1.4 log , 0.8 - 2.1 , p=0.001 ) . All three sustained responders had undetectable plasma HCV RNA at day 14 . CONCLUSION In patients without a response to st and ard interferon , the hepatitis C virus has a high daily turnover rate similar to that reported in naive patients . Our findings suggest that an early clearance of HCV RNA from the circulation is the key to a sustained response , which might be induced in about 25 % of these patients by treatment with high ( 10 MU ) daily doses of interferon . These findings have important implication s for the concept of treatment of hepatitis C , which should shift its focus from long-term mild treatment towards aggressive therapy aim ing at a fast viral disappearance within the first few days AIM To compare the efficacy of a descalating dose of interferon ( 48 weeks ) versus a combination therapy of interferon and ribavirin ( 24 weeks ) in hepatitis C positive subjects who relapsed within six months of cessation of a st and ard six month course of interferon three million units thrice weekly . METHODS All 32 subjects had biopsy proven chronic hepatitis C , were PCR positive and had elevated transaminase enzymes at least one and a half times the upper limit of normal . Subjects were r and omly assigned to either a descalating dose of interferon-alpha-2a ; six million units thrice weekly for 24 weeks followed by 3 MIU 3x for 24 weeks or interferon three million units thrice weekly for 24 weeks plus ribavirin 1,000 mg/day for 12 weeks . A complete virological response was defined as a negative PCR for HCV RNA at 24 weeks after cessation of therapy . RESULTS Sixteen patients were assigned to each arm and the sustained virological response was 50 % for both the interferon and combination therapy arm ( pNS ) . The biochemical response correlated with the virological response ; 7/8 virological responders in the interferon alone had normalisation of transaminase 24 weeks post treatment as did 8/8 of those in the combination arm . One patient withdrew from treatment in the descalating interferon group and three required dose reduction . No subjects in the combination arm discontinued therapy but dose reduction was required in three subjects . CONCLUSION High dose descalating interferon-alpha 2a and a combination of interferon-alpha 2a and ribavirin were effective in achieving a sustained virological response in 50 % of subjects who had relapsed after a st and ard six month course of interferon BACKGROUND & AIMS The most effective therapy currently available for treatment of chronic hepatitis C virus ( HCV ) is the combination of peginterferon and ribavirin . This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy . METHODS The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis ( HALT-C ) Trial were evaluated . All were HCV RNA positive , previous nonresponders to interferon , with or without ribavirin , and had bridging fibrosis or cirrhosis on liver biopsy ( Ishak fibrosis stage 3 - 6 ) . Patients were retreated with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000 - 1200 mg/day . Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks . RESULTS Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20 , and 18 % achieved sustained virologic response ( SVR ) . Factors associated with an SVR included previous treatment with interferon monotherapy , infection with genotypes 2 or 3 , a lower AST : ALT ratio , and absence of cirrhosis . Reducing the dose of ribavirin from > or = 80 % to < or = 60 % of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21 % to 11 % ( P < or = 0.05 ) . In contrast , reducing the dose of peginterferon or reducing ribavirin after week 20 , when HCV RNA was already undetectable , did not significantly affect SVR . CONCLUSIONS Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin OBJECTIVES The aim of this study was to evaluate the efficacy of two different doses of alpha interferon ( IFN ) for retreatment in chronic hepatitis C patients who were non responders to initial treatment by IFN at a dose of 3 MIU TIW for 6 months . METHODS This open , pilot , prospect i ve , r and omized and bicentric study included patients with biopsy-proven chronic hepatitis C. Non response was defined as serum ALT levels > 2 upper limit of normal for the entire first treatment period , HCV RNA positivity by PCR at the end of the first treatment period , and the persistence of histologically-proven chronic active hepatitis after the first treatment period . Patients were r and omized into two groups : group I received IFN alpha 2b 10 MIU TIW for 2 months , then 6 MIU TIW for 4 months , group 2 received IFN alpha 2b 6 MIU TIW for 6 months . RESULTS Twenty three patients ( 17 male , 6 female , mean age : 38.7 + /- 9.1 years ) were included : 14 were r and omized in group 1 and 9 in group 2 . Both groups were similar for the main clinical , biochemical , and histological variables . At the end of retreatment , 2 patients ( 14.2 % ) had biochemical and virological response in group 1 and 4 in group 2 ( 44.4 % ) ( non significant ) . Only one biochemical and virological sustained response was observed in group 2 ( 11.1 % ) ( non significant ) . There was no difference between the groups for complete and sustained response . An overall statistical significant improvement of Knodell score was observed ( 7.8 + /- 3.8 vs 9.6 + /- 3.2 , P < 0.02 ) in the 18 patients who had a second biopsy 6 months after the end of therapy , while the Knodell score did not change at the end of the first treatment period . This improvement was statistically significant in group 2 ( 5.4 + /- 3.0 vs 9.2 + /- 9.5 before treatment , P < 0.02 ) and concerned intralobular necrosis ( P < 0.05 ) . The Metavir index did not change . The number of side-effects was similar in both groups . CONCLUSIONS These results suggest that histological improvement may be obtained after IFN retreatment in some patients who are non-responders to the first treatment , despite an absence of biochemical and /or virological response To improve the long-term efficacy of interferon ( IFN ) for treatment of chronic hepatitis C virus ( HCV ) infection , we proposed induction therapy with twice-a-day IFN-beta injection . This study was intended to clarify the antiviral mechanism . Thirty patients were r and omly assigned to two groups : group A ( twice-a-day therapy ) received 3 MU IFN-beta intravenously ( i.v . ) twice a day for 2 weeks ; group B ( once-a-day therapy ) received 6 MU of IFN-beta daily . HCV RNA , IFN-beta , alanine aminotransferase ( ALT ) , 2'5'-oligoadenylate synthetase ( 2'5'-AS ) activity , and beta2-microglobulin in serum were compared between the two groups during the first 2 weeks of IFN therapy . The clearance rate of serum HCV RNA in group A ( 86.7 % ) was significantly higher than that in group B ( 13.3 % ) at day 3 ( p = 0.0006 ) . No accumulation of IFN-beta was shown in serum throughout the therapy . The ratio ( day 3/day 1 ) of 2'5'-AS activity was significantly higher in group A. Multivariate analysis indicated twice-a-day IFN-beta injection therapy led to significantly early clearance of circulating HCV . Twice-a-day IFN-beta injection therapy could induce biologically enhanced antiviral activities and be an efficient induction therapy for eradication of HCV BACKGROUND Effectiveness of combination therapy with st and ard interferon alpha doses and ribavirin is far from being demonstrated in patients with hepatitis C non responders to interferon alpha monotherapy . Recent kinetic studies revealed that these doses may be suboptimal . AIMS To find the criteria for optimisation of the interferon dose , to be used in combination with ribavirin in patients with hepatitis C non responders to interferon alpha monotherapy . PATIENTS Sixty-three patients enrolled in a pilot controlled trial were treated for 6 months with ribavirin ( [ 1000 - 1200 mg daily ) and were r and omised to concurrently receive interferon alpha 2b for 6 months at : 3 Million Units thrice weekly [ group A ( 21 patients ) ] , 5 MU thrice weekly [ group B ( 21 patients ) ] and 5 million units daily [ group C ( 21 patients ) ] . RESULTS A sustained virological response was observed in : 1 patient from group A ( 5 % ) , 2 patients from group B ( 9 % ) and 8 patients from group C ( 38 % ; p=0.02 vs group A ; p=0.03 vs group B ) . Side-effects were not significantly different between the 3 groups . Multivariate analysis showed that infection by hepatitis C virus genotypes 2 or 3 and interferon alpha dosage of 5 million units daily were independent predictors of sustained response . CONCLUSIONS These results suggest that higher interferon doses administered daily in combination with ribavirin could be more effective in those patients with hepatitis C who had not responded to interferon alone PURPOSE To assess the efficacy of interferon alpha-2b and ribavirin in combination in the treatment of patients with chronic hepatitis C who had either failed to respond to therapy with interferon alpha ( nonresponders ) , or who had relapsed after interferon therapy ( relapsers ) . SUBJECTS AND METHODS Four hundred patients with chronic hepatitis C ( 200 nonresponders and 200 relapsers ) were r and omly assigned in equal numbers to receive either subcutaneous administration of recombinant interferon alpha-2b ( 3 million units three times per week ) and ribavirin ( 1,000 to 1,200 mg/daily orally ) or interferon alpha-2b alone ( 6 million units three times per week ) . Both ribavirin and interferon alpha-2b were given for 24 weeks . The patients were then followed for an additional 24 weeks . RESULTS At the end of the treatment period , normalization of serum alanine aminotransferase levels and absence of hepatitis C virus RNA were seen in 21 % of nonresponders and in 39 % of relapsers who were treated with interferon alpha-2b and ribavirin , compared with 5 % of nonresponders ( P = 0.001 ) and 9 % of relapsers treated with interferon alpha-2b alone ( P < 0.001 ) . At the end of follow-up , 14 % of nonresponders and 30 % of relapsers treated with the combination therapy had a sustained response , compared with 1 % of nonresponders ( P = 0.001 ) and 5 % of relapsers treated with interferon alpha alone ( P < 0.001 ) . CONCLUSIONS A 24-week course of treatment with interferon alpha-2b and ribavirin offers a chance of sustained response , whereas retreatment with interferon alpha-2b alone does not give satisfactory results . The role of long-term therapy in inducing prolonged remission remains to be explored Patients with chronic active hepatitis C and cirrhosis often develop hepatocellular carcinoma . Interferon ( IFN ) seems to be effective in some patients but whether it prevents carcinogenesis is unknown . In a prospect i ve r and omised controlled trial , we evaluated the effects of IFN-alpha in cirrhotic patients with HCV infection because of their high risk of hepatocellular carcinoma . 90 patients with compensated chronic active hepatitis C with cirrhosis were r and omly allocated to receive IFN-alpha ( 6 MU three times weekly for 12 - 24 weeks ) ( 45 patients ) or symptomatic treatment ( 45 controls ) , and were followed up for 2 - 7 years . In nine controls , alanine aminotransferase ( ALT ) decreased to less than 80 IU/L but did not stay in the normal range . In 19 patients given IFN-alpha , ALT decreased to less than 80 IU/L ( in seven patients , it became and stayed normal ; p = 0.011 , Wilcoxon rank-sum test ) . However , the mean change in ALT was not significantly different between the two groups . The mean change in peak alpha-fetoprotein values was smaller in patients given IFN-alpha than in controls ( p = 0.021 ) . The mean change in the serum albumin level was higher in the IFN-alpha group ( p < 0.001 ) . The histological activity index in the 12 IFN-alpha patients undergoing a second biopsy after therapy was improved ( p = 0.031 ) . Hepatitis C viral RNA disappeared in seven ( 16 % ) of the 45 IFN-alpha patients ( 95 % CI , 7 - 29 % ) and in none of the 45 controls ( 0 - 8 % ; p = 0.018 ) . Hepatocellular carcinoma was detected in two ( 4 % , 1 - 15 % ) IFN-alpha patients and 17 ( 38 % , 24 - 54 % ) controls ( p = 0.002 , Wilcoxon signed-rank test ) . The risk ratio of IFN-alpha treatment versus symptomatic treatment was 0.067 ( 0.009 - 0.530 ; p = 0.010 Cox 's proportional hazards ) . IFN-alpha improved liver function in chronic active hepatitis C with cirrhosis , and its use was associated with a decreased incidence of hepatocellular carcinoma Retreatment of chronic hepatitis C patients nonresponders to interferon ( IFN ) alone with the st and ard dose of IFN [ 3 million units ( MU ) thrice weekly ( TIW ) ] plus ribavirin for 24 weeks has yielded low sustained virological response ( SVR ) , averaging 8 % . The aim of the present , open-labelled , r and omized study was to evaluate the efficacy of IFN induction therapy followed by prolonged high dose of IFN plus ribavirin in nonresponders . One hundred and fifty-one patients were r and omized to receive 5 MU daily of IFN alfa-2b ( group 1 , n = 73 ) or 5 MU TIW of IFN alfa 2b ( group 2 , n = 78 ) for 4 weeks followed by IFN ( 5 MU TIW ) plus ribavirin ( 1000/1200 mg/daily ) for 48 weeks in both groups . In an intention-to-treat analysis , the sustained virological response ( SVR ) at 24-week follow-up was 33 and 23 % for group 1 and 2 , respectively ( P = 0.17 ) . The overall SVR was 52 and 18 % in patients with genotype 2/3 and 1/4 , respectively . Among genotype 1/4 patients the SVR was 29 and 11 % for age younger or older than 40 years . Compared with genotype 2/3 patients , the risk ( 95 % confidence interval ) of nonresponse to retreatment was 3.0-fold ( 1.17 - 8.0 ) in younger genotype 1/4 patients and 8.4-fold ( 3.0 - 23.29 ) in older genotype 1/4 patients . In conclusion these results suggest that retreatment with a reinforced regimen should be focused in nonresponder genotype 2/3 patients and younger genotype 1/4 patients , who are most likely to benefit . Induction therapy does not improve SVR BACKGROUND Little is known about the therapeutic role of intravenous interferon-beta in chronic hepatitis C patients unresponsive to a previous treatment with interferon-alpha . METHODS Two hundred interferon-alpha non-responders were r and omized to receive either intravenous recombinant interferon-beta or interferon-alpha-2b and ribavirin for 12 weeks . The responders in both groups were followed up for a further 48 weeks . RESULTS At week 12 a biochemical and virologic response was documented in 42 % of the patients treated with interferon-beta and in 22 % of the patients treated with combination therapy . A sustained response was observed in 21 % of the patients treated with interferon-beta and in 13 % of those treated with combination therapy , with similar differences on intention-to-treat analysis . CONCLUSIONS Short-term treatment with intravenous interferon-beta seems to offer a chance for sustained response in a subset of interferon-alpha non-responders . The role of long-term therapy in these patients still remains to be explored Non-responders to 6-months treatment with recombinant interferon (rIFN)-alpha , 3 MU thrice weekly ( primary non-responders ) were treated for 6 further months with the same therapy or with a double dose of rIFN-alpha or with a different type of IFN ( L-IFN ) . 112 primary non-responders were r and omly enrolled into four groups of 28 patients each over a period of 4 years and were followed up for 6 months : group A continued the same dose of rIFN-alpha , group B was treated with the same rIFN-alpha but received a double dose ( 6 MU thrice weekly ) , group C received L-IFN , 3 MU thrice weekly , and group D stopped IFN therapy and did not receive any treatment . Patients were examined at monthly intervals and response was defined as a complete normalization of alanine amino transferase ( ALT ) . The four groups were homogeneous as to age , sex , duration of the disease , probable source of infection , histological diagnosis . ALT and gamma glutamyl transferase ( gamma GT ) levels . No patient discontinued therapy for side-effects . Further treatment with rIFN-alpha 3 MU thrice weekly ( group A ) induced normalization of ALT levels in four patients ( 14 % ) ; treatment with double-dosed rIFN-alpha ( group B ) induced normalization of liver enzymes in six cases ( 21 % ) ; a different type of interferon ( L-IFN ) ( group C ) achieved normalization of serum ALT in five patients ( 18 % ) . None of 28 primary non-responders who did not receive any treatment ( group D ) showed normalization of ALT levels . None of the patients was anti-HCV negative at the end of the study and no statistically significant difference was noted between responders and non-responders to the second course of IFN therapy as to age , sex , duration of the disease . ALT and gamma GT levels at the end of the trial . Overall at the end of the study the primary non-responders with normal levels of ALT were 15/112 ( 13 % ) , with a therapeutic advantage of 7 % . No statistically significant difference in the response rate was found among patients who continued IFN therapy , but prolongation of rIFN-alpha treatment at double dosage seems to be the best therapeutic regimen OBJECTIVE : Interferon combined with ribavirin has efficacy in the treatment of patients with chronic hepatitis C virus ( HCV ) infection . However , its utility in patients who have not responded to prior interferon therapy is not clear . Furthermore , the effect of using an increased dose of interferon in combination with ribavirin in patients with chronic hepatitis C resistant to conventional doses of interferon is not known . The aim of our study was to evaluate the effect of high-dose interferon in combination with ribavirin on the efficacy of treating patients with chronic hepatitis C resistant to interferon monotherapy in a large multicenter trial . METHODS : We r and omized 154 patients with chronic hepatitis C who failed to achieve a sustained response with prior interferon therapy to receive either 3 or 5 MU of interferon α-2b and ribavirin ( 1000–1200 mg/day ) for 12 months . There were 119 patients who had not responded and 35 who initially responded but relapsed after prior interferon monotherapy . Serum HCV RNA levels were measured at entry , 6 , and 12 months of treatment and at the end of a 6-month follow-up period . RESULTS : The mean age of the subjects was 47 yr ( range 28–68 yr ) , and 110 ( 71.4 % ) were men . One hundred thirty-two patients ( 86 % ) had HCV genotype 1 , whereas 21(14 % ) had cirrhosis . Eighty-one subjects ( 53 % ) were r and omized to receive 3 MU of interferon α-2b . Fifteen of 35 relapse subjects ( 43 % ) and 12 of 119 prior nonresponder entrants ( 10 % ) achieved a sustained virological response to the 12-month course of treatment . Overall , 11 of 81 patients ( 14 % ) receiving 3 MU , and 16 of 73 patients ( 22 % ) receiving 5 MU of interferon maintained an undetectable HCV RNA level after cessation of therapy . The difference in sustained response rates between the two interferon dosage groups did not reach statistical significance ( p = 0.09 ) . However , among the nonresponder patients alone , there was an increased sustained response in the high-dose interferon group compared with the st and ard interferon dose group ( 15.5 % vs 4.9 % , p = 0.055 ) . Twenty-six patients discontinued therapy before 6 months , including 10 patients ( 12.3 % ) in the 3-MU and 16 patients ( 21.9 % ) in the 5-MU groups ( p = 0.17 ) . Conclusions : Sustained virological response to combined interferon α-2b and ribavirin was significantly higher in relapse patients than those who did not respond to prior interferon monotherapy . Although , when all treated patients were analyzed , there was no significant difference in sustained response between subjects receiving 3 and 5 MU of interferon , among the prior nonresponder patients , treatment with 5 MU of interferon with ribavirin result ed in a slightly increased response compared with treatment with the st and ard interferon dosage . The tolerability of the treatment regimens was comparable In chronic hepatitis C , previous data have shown that short-term treatment with interferon-alpha ( IFN-alpha ) can reduce collagen deposition in the liver independently of the viral response . The aim of this work was to determine , in non-responder patients , the long-term effect of IFN-alpha on liver fibrosis according to the total administered dose and the fibrotic stage . Fibrosis was investigated on liver biopsies from 24 non-responder patients with chronic hepatitis C retreated with successive courses of IFN-alpha . The degree of liver fibrosis was assessed on three successive biopsies , performed before IFN-alpha treatment and 1 and 5 years later , in 13 and 11 patients , respectively , treated for less ( mean : 7.5 months , 313 MU ) and more ( mean : 21.8 months , 791 MU ) than 1 year . For each biopsy , fibrosis was assessed using a histological semiquantitative fibrosis scoring system and by morphometry after picrosirius red staining . Regardless of the dose and duration of IFN-alpha therapy , a slight decrease of fibrosis was observed in patients 5 years after starting treatment . In cirrhotic patients , a short treatment induced an improvement followed by a relapse of fibrosis in 57 % , and only 43 % of patients showed constant collagen regression over the 5 years of follow-up . On the contrary , after prolonged therapy , a progressive and significant decrease occurred throughout the follow-up period in all patients ( P = 0.045 ) . Long-term treatment with IFN-alpha is therefore associated with regression of liver fibrosis , particularly in cirrhotic patients . These promising results need to be confirmed in a larger series of patients Chronic hepatitis C is a major cause of cirrhosis and hepatocellular carcinoma . Spontaneous remission of the disease seems to be rare , but interferon- therapy induces a response characterized by normalization of aminotransferase levels and improvement of liver histologic findings in 38 % to 48 % of patients [ 1 - 6 ] . However , more than half of responders have relapse and a reincrease of serum aminotransferase levels within 6 months after withdrawal of interferon- therapy . Less than 20 % of treated patients have a sustained response with persistently normal aminotransferase levels during the 6-month period after treatment . Long-term outcome in patients with sustained response is not well known . A few studies of small numbers of patients with follow-up periods of 1 to 4 years have suggested a long-term benefit in some patients ; however , late relapse was seen in other studies [ 7 - 13 ] . Little information is available on histologic outcome , and the question of the long-term benefit of interferon- therapy with regard to hepatic viral clearance and histologic improvement remains to be answered . To address this question , we assessed the long-term biochemical , virologic , and histologic outcomes of 80 patients with chronic hepatitis C who had a sustained response during the 6 months after interferon- therapy . Methods Patients Among 450 patients with chronic hepatitis C who received interferon- therapy in our center between 1987 and 1993 , 80 consecutive patients who had a sustained response after therapy were included in our study . Sustained response was defined as 1 ) strictly normal serum alanine aminotransferase [ ALT ] levels each month for the first 6 months after the end of therapy and 2 ) negative results on testing for serum hepatitis C virus ( HCV ) RNA 6 months after treatment . The 80 patients were followed for at least 1 year after the end of treatment ; further follow-up was considered long-term follow-up . Of these 80 patients , 50 were treated in six r and omized , controlled trials of interferon- . Twenty-two received recombinant interferon-2b(Intron A , Schering-Plough , Levallois , France ) at a dose of 3 or 5 million U [ 4 , 6 , 14 ] ; 19 received lymphoblastoid interferon- ( Wellferon , Wellcome , Issy-les-Moulineaux , France ) at a dose of 3 or 5 million U [ 15 , 16 ] ; and 9 received recombinant interferon-alpha2a ( Roferon-A , Produits Roche , Neuilly , France ) at a dose of 3 million U [ 17 ] . The six trials were approved by the ethical committee , and all patients gave informed consent . The 30 patients who did not participate in the trials received the licensed st and ard schedule for interferon- therapy : recombinant interferon-alpha2a or -alpha2b , 3 million U three times a week for 6 months . Treatment schedules are shown in Table 1 . Table 1 . Demographic , Biochemical , Virologic , and Histologic Characteristics before Treatment and Treatment Schedule in 80 Patients with Chronic Hepatitis C and Sustained Response to Interferon- Therapy * All patients had chronic hepatitis C shown on biopsy within 6 months before treatment ; the mean histology score ( SD ) was 7.9 2.2 ( range , 3 to 13 ) . All patients had serum ALT levels greater than 1.5 times the upper limit of normal for at least 6 months , and all were negative for hepatitis B surface antigen and antibodies to HIV . Follow-up Follow-up included clinical assessment every 6 months , measurement of serum ALT levels at least every 3 months , and detection of serum HCV RNA by polymerase chain reaction ( PCR ) every 6 months . Antibodies to Hepatitis C Virus Before treatment , all patients were positive for antibodies to HCV . Antibody testing ( done retrospectively for patients treated before 1990 ) was done by using second-generation enzyme-linked immunoassay and Recombinant Immunoblast Assay ( Ortho Diagnostic Systems , Levallois , France ) . Serum Hepatitis C Virus RNA We tested for the presence of serum HCV RNA in all 80 patients on serum specimens that were kept frozen and collected 6 months after withdrawal of interferon- therapy and then every 6 months during the entire follow-up period . Serum HCV RNA was detected by using PCR ( Amplicor HCV , Produits Roche ) [ 18 ] . Serum HCV RNA quantitation was performed with the quantitative branched-DNA signal amplification assay ( Quantiplex HCV RNA , Chiron Diagnostics , Eragny , France ) before treatment in 62 patients for whom pretreatment serum HCV RNA measurements were available and during follow-up in patients with persistent or fluctuating detectable HCV RNA levels [ 19 ] . Genotype and Serotype of Hepatitis C Virus We did HCV genotyping in 62 patients for whom pretreatment serum measurements were available . Genotyping was done by using the reverse hybridization assay ( LiPA , InGeN , Rungis , France ) after amplification with the PCR assay [ 20 ] . The classification system of Simmonds and colleagues was used [ 21 ] . In 18 patients who had no pretreatment serum aliquots available and whose post-treatment serum specimens were negative on PCR , HCV genotyping was not possible and HCV serotyping was done . Serotyping was performed with an immunoenzymatic assay that shows antibodies directed to peptides encoded by the NS4 region of the HCV genome , which are specific for serotypes 1 , 2 , 3 , 4 , 5 , and 6 ( Murex Diagnostics , Chatillon , France ) [ 22 ] . These serotypes are classified according to the respective genotypes in the classification system of Simmonds and colleagues [ 21 ] . Liver Histologic Studies Liver biopsy was done at the end of interferon- therapy or 6 or 12 months after therapy , according to the relevant protocol , in patients who participated in the r and omized trials . Another biopsy was done 1 to 6 years after therapy in all patients . Biopsy specimens obtained before and after treatment were assessed for fibrosis ( score , 0 to 4 ) and activity ( score , 0 to 18 ) according to the scoring system of Knodell and coworkers [ 23 ] . Chronic hepatitis C was defined as mild if the total histology score was less than 6 , moderate if the score was between 6 and 9 , and severe if the score was greater than 9 . Biopsy specimens obtained by using a percutaneous Menghini needle were at least 10 mm long . Specimens were coded and were assessed by one pathologist . After interferon- therapy , 109 liver biopsies were done in 69 of the 80 patients ( 32 patients had 2 biopsies , and 4 patients had 3 biopsies ) ; 22 were done at the end of treatment and 87 were done during follow-up . In 48 of the 69 patients , the last post-treatment biopsy was done at least 1 year after the end of interferon- treatment ( 2.2 1.3 years [ range , 1 to 6.2 years ] ) . In these 48 patients , histologic outcome was assessed by comparing the pretreatment biopsy specimen with the last biopsy specimen obtained after treatment . Histologic outcome was defined as improved if the total histology score was at least 2 points lower in the post-treatment specimen , as no change if the score was 1 point lower in the post-treatment specimen or was the same in the two specimens , and as deterioration if the score was higher in the post-treatment specimen . Liver Hepatitis C Virus RNA A liver tissue specimen was collected 1 to 5 years after treatment in 27 patients ( 2 years after treatment in 10 patients ) ; 13 of the 27 had a liver tissue specimen collected before treatment . All tissue sample s were immediately frozen in liquid nitrogen and kept at 80C . All tubes and tissue grinders used for the liver HCV RNA extraction procedure were disposable and sterile and were autoclaved . Liver RNA was extracted with the guanidium isothiocyanate procedure ( Trizol , Appligen , Illkirch , France ) , and PCR was performed in the 5NC region of the HCV genome according to the methods of Martinot-Peignoux and associates [ 24 ] . The quality of the extracted liver RNA was ascertained with the amplification of the cellular 28S ribosomal messenger RNA ( rRNA ) [ 25 ] . The 28S rRNA represents 80 % of the total cellular RNA ; the presence of 28S rRNA attested to the good preservation of the liver specimens . Specimens without amplifiable 28S rRNA were excluded from our study . All PCR assays were done in the presence of negative and positive controls , which were liver tissue specimens collected during the period in which the study specimens were collected . Negative controls were obtained from patients without antibodies to HCV and patients without detectable serum HCV RNA who had chronic liver disease . Positive controls were obtained from patients with untreated chronic hepatitis C. At each step of the procedure , a negative specimen without nucleic acid was added . All PCR procedures on liver and serum were done with strict application of the measures described by Kwok and Higuchi [ 26 ] . Role of the Funding Source The funding source did not influence the analysis or interpretation of the data or the decision to su bmi t the paper for publication . Results In our 80 patients with chronic hepatitis C , a sustained response was defined by 1 ) a persistently normal serum ALT level throughout the 6-month post-treatment follow-up period and 2 ) negative results on serum HCV RNA testing 6 months after treatment . Patients were followed for 1 to 7.6 years after the end of interferon- therapy ( mean SD , 4.0 2.0 years ) . The characteristics of the 80 persons with sustained response are shown in Table 1 . The numbers of patients contributing data at each time point during follow-up are shown in Table 2 . Table 2 . Patients Contributing Data at Each Time Point during Follow-up * Clinical Outcomes At the end of follow-up , 79 of the 80 persons with sustained response were fully active and alive ; 1 had died of peritoneal carcinomatosis related to colon carcinoma . Of the 5 patients with cirrhosis , none developed decompensated liver disease or hepatocellular carcinoma as assessed by abdominal ultrasonography done every 6 months . Of the 75 patients who did not have cirrhosis before receiving interferon- therapy , none developed cirrhosis . All patients who had fatigue before treatment ( 60 % ) said that the fatigue completely disappeared after BACKGROUND / AIMS A sustained biochemical and virologic response to st and ard interferon therapy for chronic hepatitis C is seen in no more than 25 % of patients , and the efficacy of re-treatment or of higher doses in non-responders and relapsers has not been established . A more effective therapy for interferon alfa-resistant hepatitis C is needed . METHODS A study of ribavirin plus interferon alfa combination therapy was conducted in 30 patients with chronic hepatitis C resistant to a previous st and ard course of interferon alfa ( 14 interferon non-responders , 16 interferon relapsers ) . Patients were r and omly assigned to receive either ribavirin , 800 mg daily , and interferon alfa , 3 MU thrice weekly ( n = 15 ) , or interferon alfa alone , 3 MU thrice weekly ( n = 15 ) , for 6 months . RESULTS At the end of treatment , normal alanine aminotransferase levels were observed in eight patients in the combination therapy group : one ( 14 % ) interferon non-responder and seven ( 87 % ) interferon relapsers ( p = 0.01 ) . Six months post-therapy , sustained normalization of alanine aminotransferase was achieved in seven ( 87 % ) interferon alfa relapsers , but not in any of the interferon alfa non-responders ( p = 0.001 ) . In the group of patients treated with interferon alfa alone , sustained normalization of alanine aminotransferase was observed in one interferon relapser only . Serum HCV RNA became negative in eight patients receiving combination therapy -- two ( 28 % ) interferon non-responders and six ( 75 % ) interferon relapsers . Six months later , circulating HCV RNA remained negative in seven patients : one ( 14 % ) interferon non-responder and six ( 75 % ) interferon relapsers ( p = 0.04 ) . Sustained clearance of HCV RNA was not observed in patients re-treated with interferon alone . The sustained response to combination therapy was accompanied by reduced hepatic necroinflammatory activity on liver biopsy . Hepatitis C virus genotype was not significantly associated with response to combination therapy . Side effects were mild and well tolerated . CONCLUSIONS Our experience indicates that combination therapy of ribavirin plus interferon alfa induces sustained biochemical , virologic , and histologic responses in most patients who are interferon relapsers The aim of this study was to examine whether 78 week course of interferon ( IFN ) retreatment could improve the beneficial effect of IFN in chronic hepatitis C patients compared with 52 week course of IFN retreatment . Inclusion criteria were biopsy-proven chronic hepatitis , serum HCV-RNA level of more than 1 Meq/ml , HCV-genotype 1b , abnormal serum alanine aminotransferase ( ALT ) , and transient negative conversion for HCV-RNA during the initial course of IFN therapy . Forty-one patients were r and omly assigned to two groups , receiving total doses of : 1410 MU for 52 weeks ( a 52 week-group : n=20 ) , or 1995 MIU for 78 weeks ( a 78 week-group : n=21 ) . But three patients ( one in the 52 week-group and two in the 78 week-group ) were withdrawn from the study due to a transfer , refusal after r and omization , and occurrence of malignant lymphoma before IFN retreatment , respectively . Therefore remainder 38 patients were studied about efficacy of IFN administration . A virological response ( VR ) to IFN therapy was defined as HCV-RNA negativity by the reverse transcription nested polymerase chain reaction both 3 and 6 months after the completion of IFN retreatment . A biochemical response ( BR ) was defined as normalization of ALT but positive HCV-RNA both 3 and 6 months after the cessation of IFN therapy . According to these criteria , VR was 36.8 % ( 7/19 ) in the 52 week-group and 21.1 % ( 4/19 ) in the 78 week-group . BR was 5.3%(1/19 ) in the 52 week-group and 21.1 % ( 4/19 ) in the 78 week-group . There was no significant difference between the 52 week-group and the 78 week-group with respect to the effect of IFN . We conclude that 52 week course of IFN retreatment may be a sufficient strategy if patients , who have HCV-genotype 1b and high virus load , show negative HCV-RNA and normal ALT level during the first IFN therapy Interferon-alpha ( IFN-alpha ) induces sustained remission of chronic hepatitis C in approximately 25 % of patients . In patients who are non-responders to the first course of therapy , retreatment with IFN-alpha is of limited efficacy . Ribavirin has also been used to treat chronic hepatitis C , but it induces only a transient response . In this study , we evaluated the efficacy of ribavirin and IFN-alpha combination therapy for IFN-alpha resistant chronic hepatitis C. Twenty-four IFN-alpha non-responders and 24 relapsers were r and omized to receive either ribavirin ( 1000 mg per day ) together with IFN-alpha ( 3 - 6 million units ( MU ) thrice weekly ) or the same dose of IFN-alpha alone , for 6 months . Both at the end of treatment and 6 months later , normal transaminase levels were more common in the patients receiving combination therapy than in the group receiving IFN-alpha alone : 17 ( 70.8 % ) vs seven ( 29.2 % ) patients ( P = 0.009 ) and six ( 25 % ) vs one ( 4.2 % ) patient ( P = 0.034 ) , respectively . At the end of treatment and 6 months later , serum HCV RNA was no longer detectable in eight ( 33.3 % ) and five ( 20.8 % ) patients in the combination therapy group and in six ( 25 % ) and one ( 4.2 % ) patient in the IFN-alpha therapy group , respectively . Three patients ( 12.5 % ) were withdrawn prematurely from combination therapy because of side-effects ; ribavirin therapy was ceased or dosage reduced in six other patients ( 25 % ) , again because of side-effects . In conclusion , this combination treatment was more effective than retreatment with IFN-alpha , alone , in inducing sustained biochemical remission of chronic hepatitis C that was resistant to a previous course of IFN-alpha . The combination treatment , however , was frequently associated with significant side-effects We assessed the efficacy of interferon ( IFN ) alpha-2b plus ribavirin therapy in patients with hepatitis C virus (HCV)-related cirrhosis , and eluci date d the risk factors for the development of hepatocellular carcinoma ( HCC ) to determine whether these therapies might reduce the incidence of HCC . One hundred and thirty-two HCV-cirrhotic patients receiving IFN alpha-2b ( 3 or 5 MU thrice weekly ) and oral ribavirin ( 1,000 - 1,200 mg/day ) for 24 or 48 weeks were analysed . Cumulative incidence of HCC was estimated by the Kaplan-Meier method . The prognostic relevance of clinical variables and HCC occurrence was evaluated by univariate analysis with the log-rank test and by multivariate Cox 's regression analysis . A total of 116 patients completed the treatment and 73 ( 55 % ) achieved a sustained virological response ( SVR ) . Stepwise logistic regression analysis showed that nongenotype 1b ( P < 0.001 ) and low viral load ( P = 0.018 ) were independent variables of SVR . During a median follow-up period of 37 ( 12 - 63 ) months , HCC developed in 11 patients with non-SVR and five with SVR ( P = 0.0178 ) , whereas there was no difference between those with transient biochemical response and nonresponse ( P = 0.5970 ) . The Kaplan-Meier method also showed that old age ( > or=60 years ) ( P = 0.0034 ) and genotype 1b ( P = 0.0104 ) were associated with HCC occurrence . Using Cox 's regression analysis , non-SVR ( odds ratio = 3.521 , P = 0.036 ) , male ( odds ratio = 6.269 , P = 0.011 ) and old age ( odds ratio = 3.076 , P = 0.049 ) were independent significant risk factors contributing to HCC development . Our results suggest that achieving SVR by IFN alpha-2b plus ribavirin therapy may decrease the incidence of HCC in patients with HCV-related cirrhosis BACKGROUND : Interferon ( IFN ) retreatment for hepatitis C virus ( HCV ) relapsers has been effective under some conditions . We conducted a r and omized , controlled trial of IFN beta retreatment for HCV relapsers after IFN alpha . PATIENTS AND METHODS : We gave IFN beta 6MIU therapy to 43 patients who had relapse of HCV after the 24 weeks IFN alpha monotherapy . The 43 patients were r and omly assigned to two groups : Group A started retreatment within 4 weeks after relapse ; and Group B started retreatment 24 weeks or more after relapse . RESULTS : Nine patients showed sustained virological response ( SR ) to the retreatment . All of these patients were in a low viral load subgroup . The SR rate in Group A ( 8/22 , 36 % ) was significantly higher than in Group B ( 1/21 , 5 % ) ( P=0.0128 ) . Among patients with lower viral load , the SR rate in Group A ( 8/10 , 80 % ) was also significantly higher than in Group B ( 1/8 , 13 % ) ( P=0.0076 ) . CONCLUSION : The retreatment with IFN beta is effective for patients with HCV low viral load , and the sooner after the relapse the retreatment is started , the better the clinical results will be Chronic infection with hepatitis C virus ( HCV ) may result in cirrhosis , liver failure , and hepatocellular carcinoma . A minority of patients have a sustained response to antiviral therapy , and nonresponders remain at risk of developing progressive liver disease . We conducted a r and omized , controlled trial of therapy with the combination of interferon ( IFN ) and ribavirin in patients with chronic hepatitis C who had not responded to an initial course of therapy with IFN alone . A total of 124 patients were r and omized to receive the combination of IFN and ribavirin for either 24 or 48 weeks and followed for an additional 24 weeks after stopping therapy . Thirty-eight treated patients ( 30.6 % ) achieved a sustained virologic response ( undetectable HCV RNA at the 24-week follow-up point ) . This was associated with significant improvement in necroinflammatory activity noted on liver biopsy . Interestingly , there was not a statistically significant difference in response rates based on the duration of treatment ; HCV genotype was the strongest predictor of a sustained response . Sustained responses were noted even in patients with poor predictive factors , including those with advanced hepatic fibrosis or cirrhosis , high levels of HCV RNA in serum , and those infected with HCV genotype 1 . The study included 24 patients with normal serum alanine transaminase ( ALT ) values before therapy who had similar responses to those with initially elevated transaminase values . This study suggests that the combination of IFN and ribavirin is a useful modality of therapy in patients with chronic hepatitis C who did not respond to IFN alone UNLABELLED Chronic hepatitis C virus infection can cause chronic liver disease , cirrhosis and liver cancer . The Hepatitis C Antiviral Long-term Treatment against Cirrhosis ( HALT-C ) Trial was a prospect i ve , r and omized controlled study of long-term , low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy . The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients . Deaths occurring during and after the HALT-C Trial were review ed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon . Rates of liver transplantation were also assessed . Over a median of 5.7 years , 122 deaths occurred among 1,050 r and omized patients ( 12 % ) , of which 76 were considered liver-related ( 62 % ) and 46 nonliver-related ( 38 % ) ; 74 patients ( 7 % ) underwent liver transplantation . At 7 years the cumulative mortality rate was higher in the treatment compared to the control group ( 20 % versus 15 % , P = 0.049 ) ; the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum ( 14 % versus 7 % , P = 0.01 ) ; comparable differences were observed when liver transplantation was included . Excess mortality , emerging after 3 years of treatment , was related largely to nonliver-related death ; liver-related mortality was similar in the treatment and control groups . No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon . CONCLUSION Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality , which was primarily due to nonliver-related causes among patients with bridging fibrosis BACKGROUND & AIMS Approximately 75%-85 % of patients with chronic hepatitis C virus ( HCV ) infection do not have a sustained response when treated with interferon ( IFN ) . Limited information exists on the efficacy of retreatment with IFN alone in these patients . The aim of this study was to define the efficacy of IFN retreatment in chronic hepatitis C. METHODS Ninety-two patients with chronic hepatitis C who had shown transient or no response to recombinant IFN-alpha were r and omly retreated with different schedules of lymphoblastoid IFN-alpha and followed up for 12 months after therapy to define biochemical and virological response . RESULTS None of 26 initial nonresponders obtained a sustained response with retreatment , independent of the schedule used . Thirteen of 66 patients ( 20 % ; 95 % confidence interval [ CI ] , 10.9 - 31.3 ) with transient response during the primary cycle developed a sustained biochemical and virological response when retreated , including 3 of 41 ( 7 % ; 95 % CI , 1.5 - 9.9 ) of those receiving the same schedule and 10 of 25 ( 40 % ; 95 % CI , 21.1 - 61.3 ; P < 0.004 ) of those retreated with a higher dosage and for a longer period . Shorter disease duration ( P = 0.02 ) , higher alanine aminotransferase ( P = 0.002 ) and lower gamma-glutamyltransferase levels ( P = 0.004 ) , HCV genotype other than HCV-1 ( P = 0.03 ) , and a negative serum HCV-RNA test at the end of the primary cycle ( P = 0.000 ) were associated with sustained response . CONCLUSIONS Patients with chronic hepatitis C who have a relapse after a complete response to a 6-month IFN-alpha treatment should be retreated for 12 months . Nonresponders should not be retreated with IFN alone BACKGROUND & AIMS Interferon reportedly decreases the incidence of hepatocellular carcinoma ( HCC ) in patients with chronic hepatitis C. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis ( HALT-C ) Trial showed that 4 years of maintenance therapy with pegylated interferon ( peginterferon ) does not reduce liver disease progression . We investigated whether peginterferon decreases the incidence of HCC in the HALT-C cohort over a longer posttreatment follow-up period . METHODS The study included 1048 patients with chronic hepatitis C ( Ishak fibrosis scores ≥ 3 ) who did not have a sustained virologic response ( SVR ) to therapy . They were r and omly assigned to groups given a half-dose of peginterferon or no treatment ( controls ) for 3.5 years and followed up for a median of 6.1 ( maximum , 8.7 ) years . RESULTS Eighty-eight patients developed HCC ( 68 definite , 20 presumed ) : 37 of 515 who were given peginterferon ( 7.2 % ) and 51 of 533 controls ( 9.6 % ; P = .24 ) . There was a significantly lower incidence of HCC among patients given peginterferon therapy who had cirrhosis , but not fibrosis , based on analysis of baseline biopsy sample s. After 7 years , the cumulative incidences of HCC in treated and control patients with cirrhosis were 7.8 % and 24.2 % , respectively ( hazard ratio [ HR ] , 0.45 ; 95 % confidence interval [ CI ] , 0.24 - 0.83 ) ; in treated and control patients with fibrosis , incidences were 8.3 % and 6.8 % , respectively ( HR , 1.44 ; 95 % CI , 0.77 - 2.69 ) . Treated patients with a ≥ 2-point decrease in the histologic activity index , based on a follow-up biopsy , had a lower incidence of HCC than those with unchanged or increased scores ( 2.9 % vs 9.4 % ; P = .03 ) . CONCLUSIONS Extended analysis of the HALT-C cohort showed that long-term peginterferon therapy does not reduce the incidence of HCC among patients with advanced hepatitis C who did not achieve SVRs . Patients with cirrhosis who received peginterferon treatment had a lower risk of HCC than controls Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus ( HCV ) . We therefore conducted a r and omized , controlled trial comparing iron reduction by phlebotomy with iron reduction followed by retreatment with interferon in 96 patients with chronic hepatitis C who had previously not responded to a course of interferon . During the initial phase when all patients were undergoing phlebotomy , we found that serum alanine transaminase ( ALT ) activities decreased but by less than 50 % from baseline in 67 patients ( 89 % ) , decreased by more than 50 % in 12 patients ( 13 % ) and became normal in 9 patients ( 9 % ) with no overall change in HCV‐RNA levels . Subsequently no patient in either treatment group achieved a sustained virologic response . Improvements in necroinflammatory changes were noted in liver biopsy specimens in those patients receiving phlebotomy plus interferon ( mean index 8.59 vs. 7.37 , P < .05 ) . A slight but not statistically significant decrease in histologic activity index was noted in those subjects treated by phlebotomy alone ( mean index 8.4 vs. 7.75 , P not significant ) . We conclude that , although prior phlebotomy therapy does not improve the rate of sustained response to interferon retreatment , it does result in less liver injury manifested by a decrease in serum transaminase activity and a slight improvement in liver histopathology |
12,838 | 21,352,155 | Sex , age , and the methods of measuring the onset and end-point of DUP and the type of service in which the studies were performed did not contribute to the heterogeneity of the mean or median DUP values .
Mean DUP is significantly prolonged by a small number of patients , and the median DUP is a poor indicator of the rate at which patients present . | AIM The aim of this study was to investigate the demographic , illness and method ological factors associated with mean and median duration of untreated psychosis ( DUP ) . | Background Previous family experience of psychotic illness may play an important role in whether and when a patient seeks help in first-episode psychosis . This study investigated the relationship between family experience of psychosis and the duration of untreated psychosis in a prospect i ve sample of first-episode psychosis patients in Hong Kong . We also studied the effects of pre-morbid adjustment , educational level , living alone , and mode of onset as potential determinants of the duration of untreated psychosis ( DUP ) . Methods A total of 131 first-episode psychosis patients in Hong Kong were recruited in a study of the DUP and related factors . The Interview for the Retrospective Assessment of the Onset of Schizophrenia ( IRAOS ) was used to measure the DUP and to provide a structured assessment of family history , educational level , household arrangement , and mode of onset . Results Previous family experience of psychiatric illness ( the presence of another family member who has been receiving psychiatric treatment ) and an acute mode of onset were significant predictors of a shorter DUP . Educational level had a modest effect on its own , but was not significant in the binary logistic regression model . Living alone had a moderate effect size , but was non-significant , possibly because of the small proportion of single-person households in the sample . The symptom profile , pre-morbid adjustment , and other demographic factors were not significantly related to the DUP . Conclusion In addition to the mode of onset , previous family experience plays an important role in the presentation of early psychosis . Educational efforts that target the family should be an important part of any strategy for the early detection of psychosis Some studies in first-episode schizophrenia correlate shorter duration of untreated psychosis ( DUP ) with better prognosis , suggesting that timing of treatment may be important . A three-site prospect i ve clinical trial in Norway and Denmark is underway to investigate the effect of the timing of treatment in first-episode psychosis . One health care sector ( Rogal and , Norway ) is experimental and has developed an early detection ( ED ) system to reduce DUP . Two other sectors ( Ullevål , Norway , and Roskilde , Denmark ) are comparison sectors and rely on existing detection and referral systems for first-episode cases . The study ultimately will compare early detected with usual detected patients . This paper describes the study 's major independent intervention variable , i.e. a comprehensive education and detection system to change DUP in first onset psychosis . System variables and first results from the four-year inclusion period ( 1997 - 2000 ) are described . It includes targeted information towards the general public , health professionals and schools , and ED teams to recruit appropriate patients into treatment as soon as possible . This plus easy access to psychiatric services via ED teams systematic ally changed referral patterns of first-episode schizophrenia . DUP was reduced by 1.5 years ( mean ) from before the time the ED system was instituted ( to 0.5 years ) . The ED strategies appear to be effective and to influence directly the community 's help-seeking behaviour BACKGROUND Many patients recovering from a first psychotic episode will discontinue medication against medical advice , even before a 1-year treatment course is completed . Factors associated with treatment adherence in patients with chronic schizophrenia include beliefs about severity of illness and need for treatment , treatment with typical versus atypical antipsychotic and medication side effects . METHOD In this 2-year prospect i ve study of 254 patients recovering from a first episode of schizophrenia , schizophreniform , or schizoaffective disorder we examined the relationship between antipsychotic medication non-adherence and patient beliefs about : need for treatment , antipsychotic medication benefits , and negative aspects of antipsychotic medication treatment . We also examined the relationship between medication non-adherence and treatment with either haloperidol or olanzapine , and objective measures of symptom response and side effects . RESULTS The likelihood of becoming medication non-adherent for 1 week or longer was greater in subjects whose belief in need for treatment was less ( HR=1.75 , 95 % CI 1.16 , 2.65 , p=0.0077 ) or who believed medications were of low benefit ( HR=2.88 , 95 CI 1.79 - 4.65 , p<0.0001 ) . Subjects r and omized to haloperidol were more likely to become medication non-adherent for > or=1 week than subjects r and omized to olanzapine ( HR-1.51 , 95 % CI 1.01 , 2.27 , p=0.045 ) . CONCLUSION Beliefs about need for treatment and the benefits of antipsychotic medication may be intervention targets to improve likelihood of long-term medication adherence in patients recovering from a first episode of schizophrenia , schizoaffective , or schizophreniform disorder In a Dutch treatment intervention study of patients ( n=76 ) with first psychotic episodes of schizophrenia the hypothesis tested was whether early differential treatment after an acute psychotic break improved outcome as compared with other studies . Patients had a relatively short duration of untreated psychosis . No significant effect between two treatment conditions on relapse rate was found . The 15-month intervention program kept the psychotic relapse rate as low as 15 % ; lower than comparable studies . Thus , the initial results were in support of the hypothesis . After completion of the 15 months study , patients were referred to other agencies and followed for five years . Results of the follow up study showed that the low relapse rate could not be maintained . Of the remaining 71 patients of the initial sample , 52 % had one or more psychotic relapses , 25 % developed chronic positive symptoms and 23 % did not have another psychotic episode . In addition , the level of social functioning turned out to be low : the majority of patients were dependent upon their parents , few held down a skilled or paid job and also their quality of life seemed low , results indicate that early intervention may improve short term but not long term outcome in schizophrenia . Our results also suggest that referral to other mental health agencies after intervention is not sufficient . Continuity of outpatient care , including continuity of a professional relationship , continuity of support for the family , and the continuity in management of illness , medication and stress may be a key issue in the first five years after the onset of psychosis in schizophrenia . Early recognition and intervention may not nearly be as important for outcome as continuity in care and caregivers . At present , however , it remains question able whether early intervention programs in first-episode patients with a short duration of untreated psychosis can offer the prospect of altering the course of schizophrenia without a sustained comprehensive treatment program The hypothesis that a longer duration of symptoms prior to first hospitalization is associated with a poorer treatment response was prospect ively investigated in 998 first-hospitalized schizophrenic patients . Results indicate that most indicators of outcome were worse when the duration of symptoms was long . This was also true when age , gender , as well as the acuteness of illness were controlled for in the analyses BACKGROUND There has been controversy as to whether early intervention in psychosis can improve the outcome of the disorder . AIMS To establish if there is an association between duration of untreated psychosis and the 4-year outcome of persons with a first episode of psychosis . METHOD Prospect i ve naturalistic follow-up study of the outcome of consecutive first presentations with DSM-IV psychosis attending a community-based psychiatric service . RESULTS A longer duration of untreated psychosis was associated with a significantly poorer functional and symptomatic outcome 4 years later . For schizophrenia and schizophreniform disorder , each increment in duration of untreated psychosis was associated with a 7.8 point decrease in global functioning and an increase in positive symptoms scores by 1.9 points . CONCLUSIONS This study extends the findings of short-term follow-up studies by confirming an association between duration of untreated psychosis and ' mid-term ' outcome BACKGROUND Urban and rural population s have different rates of psychotic illness . If psychosis exists as a continuous phenotype in nature , urban-rural population differences in the rate of psychotic disorder should be accompanied by similar differences in the rate of abnormal mental states characterized by psychotic or psychosislike symptoms . METHODS A r and om sample of 7076 individuals aged 18 to 64 years were interviewed by trained lay interviewers with the Composite International Diagnostic Interview . Approximately half of those with evidence of psychosis according to the Composite International Diagnostic Interview were additionally interviewed by clinicians . We investigated associations between a 5-level urbanicity rating and ( 1 ) any DSM-III-R diagnosis of psychotic disorder ( sample prevalence , 1.5 % ) , ( 2 ) any rating of hallucinations and /or delusions ( sample prevalence , 4.2 % ) , and ( 3 ) any rating of psychotic or psychosislike symptoms ( sample prevalence , 17.5 % ) . RESULTS Level of urbanicity was associated not only with DSM-III-R psychotic disorder ( adjusted odds ratio [ OR ] over 5 levels , 1.47 ; 95 % confidence interval [ CI ] , 1.25 - 1.72 ) , but also , independently , with any rating of delusion and /or hallucination ( adjusted OR , 1.28 ; 95 % CI , 1.17 - 1.40 ; clinician-assessed psychotic symptoms only : OR , 1.30 ; 95 % CI , 1.03 - 1.64 ) and any rating of psychosislike symptom ( adjusted OR , 1.18 ; 95 % CI , 1.13 - 1.24 ) . Psychotic symptoms were strongly and independently associated with psychotic disorder , regardless of the level of urbanization . CONCLUSIONS Community level of psychotic and psychosislike symptoms may be inextricably linked to the prevalence of psychotic disorder . The prevalence of abnormal mental states that facilitate development to overt psychotic illness increases progressively with level of urbanization CONTEXT Most studies on first-episode psychosis show an association between a long duration of untreated psychosis ( DUP ) and poorer short-term outcome , but the mechanisms of this relationship are poorly understood . OBJECTIVE To determine whether it is possible to reduce the DUP for first-episode patients in a defined health care area through the introduction of an early detection ( ED ) program , compared with parallel health care areas without an ED program ( No-ED ) . SETTING AND PATIENTS We included consecutive patients with a DSM-IV diagnosis of nonorganic , nonaffective psychosis coming to their first treatment in the study health care areas between January 1 , 1997 , and December 31 , 2000 . A total of 281 patients ( 76 % of the total ) gave informed consent . INTERVENTIONS The ED and No-ED health care areas offered an equivalent assessment and treatment program for first-episode psychosis . The ED area also carried out an intensive ED program . RESULTS The DUP was significantly shorter for the group of patients coming from the ED area , compared with patients from the No-ED areas ( median , 5 weeks [ range , 0 - 1196 weeks ] vs 16 weeks [ range , 0 - 966 weeks ] ) . Clinical status measured by the Positive and Negative Syndrome Scale and the Global Assessment of Functioning Scale was significantly better for patients from the ED area at start of treatment and , with the exception of Positive and Negative Syndrome Scale positive subscale , at 3 months . Multiple linear regression analyses gave no indication that confounders were responsible for these differences . CONCLUSIONS It is possible to reduce the DUP through an ED program . The reduction in DUP is associated with better clinical status at baseline that is maintained after 3 months There is overwhelming evidence that the outcome for people with schizophrenia in Western industrialised countries is inferior to that of those living in the Third World . Extended family structures , greater opportunities for social reintegration , and more positive constructions of mental illness have been offered as possible explanations for this effect . The Asian community in the UK retains many of these features as well as strong links with native cultures of origin . The issue arises as to whether similar differences in outcome may be observed in the UK . An exploratory study was undertaken , examining the early progress of schizophrenia in a first-episode sample ( n = 137 ) , and based on systematic examination of case-note data . A lower rate of relapse/readmission in the first 12 months after discharge was found in the Asian ( 16 % ) as compared with white ( 30 % ) and Afro-Caribbean ( 49 % ) patients . Available evidence suggested that speed of access to care , living with a family , and employment may account for this effect . Medication compliance may have contributed to differences in relapse between white and Afro-Caribbeans but was not a factor influencing the low rate among Asians . The limitations and strengths of case-note studies are discussed at length , and it is concluded that a prospect i ve study is warranted and would be highly instructive Objective : We describe a system of outcome evaluation for early psychosis programmes and present preliminary data . The Early Psychosis Outcome Evaluation System ( EPOES ) was design ed for use in a naturalistic , prospect i ve study of a cohort of early-episode psychosis patients . We describe patients in terms of symptoms , substance use , social functioning and family burden , and examine the effectiveness of treatment programmes . Method : Four sites in Perth , Western Australia , participated . Outcome was evaluated from three sources : case manager ( CM ) , patient ( P ) and family member ( FM ) . Seven clinical outcome measures were used : the Brief Psychiatric Rating Scale ( CM ) , Brief Symptom Inventory ( P ) , Substance Use ( CM ) ; Social Functioning Scale ( P ) ; Global Assessment Scale ( CM ) ; Burden Assessment Scale ( FM ) , and the General Health Question naire-12 ( FM ) . Measures were collected at intake ( baseline ) into a specialist early psychosis service and thereafter every 6 months until discharge from the service . Results : After the first year of data capture , 84 baseline assessment s have been completed , and 23 patients have been followed up at 6 months . Clinicians and patients reported significantly less psychopathology at 6 months . Sixty per cent of patients reported marijuana use within 3 months of baseline assessment , and 30 % amphetamine , ecstasy or cocaine use . Increased levels of psychopathology were recorded for substance-using patients . Family members ( 59 % ) reported psychological distress at baseline ; this was reduced at 6 months . Patient social functioning and family burden did not improve measurably . Conclusions : The EPOES is an effective system that provides feedback on the clinical status of early-episode psychosis patients . Both observed and self-rated psychopathology and family psychological distress , is improved after 6 months of intervention . Family burden and patient social functioning did not demonstrate improvement . Patient social functioning is an important area for treatment . Substance use is associated with poorer psychopathology . EPOES provides a feasible system of measuring outcome in early psychosis intervention Background : There is growing recognition that people presenting with psychotic symptoms for the first time need specialized treatment . The Hamilton Health Sciences Corporation , McMaster Hospital , offers one such program , the Psychotic Disorders Clinic ( PDC ) ; it addresses some of the problems posed by long waiting lists , lack of family interventions , and long-term hospitalizations . The PDC is affiliated with the Department of Psychiatry and Behavioural Neurosciences at McMaster University . The program 's goals are to provide comprehensive outpatient care and early interventions for persons in the early stages of illness and , consequently , to improve symptom control and functioning and reduce hospitalizations . Key service components include providing low dosages of antipsychotics , offering specialized family education , and supporting return to school and work setting s. Objectives : This study compared outcomes before and after enrolment in the PDC to determine whether first-episode patients achieved improved symptom control and functioning and fewer hospitalizations . Method : For a 12-month period , we followed 40 patients , aged between 16 and 45 years , who experienced their first episode of psychotic illness between 1997 and 2000 . Prospect i ve longitudinal data were collected at baseline , 3 , 6 , and 12 months . Outcome measures included symptoms , global functioning , employment rates , duration of untreated psychosis , and number of bed-days . Results : Of the patients , 37 completed the study at 6 months , and 31 at 12 months . Over the 12 months , significant improvements occurred in psychiatric symptoms ( P < 0.001 ) , global functioning ( P < 0.001 ) , and the mean number of hospital bed-days ( P < 0.001 ) . Conclusions : It is feasible for small outpatient services to provide early intervention strategies and obtain good outcomes among first-episode patients BACKGROUND Because early illness course and outcome may affect the long-term outcome of schizophrenia-spectrum disorders , it is especially important to address poor outcome in this early critical period . AIMS To evaluate whether integrated treatment compared with st and ard treatment reduced the proportion of patients with poor clinical and social outcome after 1 year . METHOD A total of 547 patients with first-episode psychosis were included in the study , 275 r and omly assigned to integrated treatment and 272 to st and ard treatment . Measures assessed psychotic symptoms and social functioning . RESULTS There was a significant beneficial effect of integrated treatment v. st and ard treatment on " any poor outcome " . Integrated treatment had a significantly better effect on " any poor outcome " in patients with schizophrenia compared with patients in st and ard treatment . CONCLUSIONS The integrated treatment significantly reduced the proportion of patients with poor clinical and social outcome compared with st and ard treatment In this study , we investigated the possible association between clinical or pharmacological variables and suicidal behavior in a sample of chronic schizophrenia or schizoaffective disorder patients . One hundred and three patients with a DSM-III-R diagnosis of chronic schizophrenia or schizoaffective disorder were studied . The sample was subdivided in two sub sample s according to the presence/absence of suicidal attempts lifetime . The main demographic and clinical variables retrospectively collected were analyzed and compared between the two groups . Attempters had a significantly higher rate of nicotine abuse or dependence ( chi-square=3.900 , df=1 , p<0.05 , Odds Ratio (O.R.)=3.4 ) , were more likely to have or have had lifetime major depressive episodes ( chi-square=10.258 , df=1 , p<0.002 , O.R.=6.5 ) , were more likely to have a duration of untreated psychosis ( DUP ) > or = 1 year ( chi-square=6.228 , df=1 , p<0.02 , O.R.=12.5 ) , and were more frequently prescribed typical antipsychotics ( chi-square=3.979 , df=1 , p<0.05 , O.R.=6.5 ) than patients without suicidal attempts lifetime . Further investigations on larger sample s and with prospect i ve design s are warranted , particularly with respect to the role of early intervention and atypical antipsychotic treatment in reducing suicide risk in schizophrenic patients OBJECTIVES To assess pre-treatment , baseline , and outcome differences of patients with early- ( onsetor = age 18 ) psychosis in an epidemiological cohort of first-episode patients . METHODS The Early Psychosis Prevention and Intervention Centre ( EPPIC ) in Australia admitted 786 FEP patients from January 1998 to December 2000 . Data were collected from patients ' files using a st and ardized question naire . Seven hundred four files were available , 61 of which were excluded owing to non-psychotic diagnoses or a psychotic disorder due to a general medical condition and 7 owing to missing data on age at onset . 636 patients were analyzed . RESULTS The mean age at onset was 21.3 years ( SD 3.6 ) ; the prevalence of early-onset psychosis was 18.6 % ( onset range 8.2 - 17.9 ) . Patients with early-onset were likely to have a slightly , but significantly worse premorbid functioning and a significantly longer duration of untreated psychosis ( Median 26.3 weeks ) compared to patients with adult-onset ( Median 8.7 weeks ; p<.001 ) . After controlling for relevant confounders , no significant outcome differences including CGI-S , GAF , remission of positive symptoms , or employment status were detected between early- and adult-onset psychoses . CONCLUSIONS Patients with early-onset psychosis may require a different approach to early detection . Outcome differences between early- and adult-onset were minor , but need to be replicated in future ( long-term ) prospect i ve epidemiological studies in other services |
12,839 | 29,958,339 | No significant effects were found on the remaining outcomes and time points .
Significant moderator effects were found for professional background of therapists , intervention concept , number of sessions , and setting .
This systematic review and meta- analysis provides evidence that adult patients with cancer across all stages and types benefit from existential interventions . | OBJECTIVES To synthesize the evidence of existential interventions in adult patients with cancer . | OBJECTIVE The aim is to evaluate the effectiveness of a manualized 12-week supportive-expressive group therapy program among primary breast cancer patients treated in community setting s , to determine whether highly distressed patients were most likely to benefit and whether therapist 's training or experience was related to outcome . METHOD Three hundred and fifty-three women within one year of diagnosis with primary breast cancer were r and omly assigned to receive supportive-expressive group therapy or to an education control condition . Participants were recruited from two academic centers and nine oncology practice s , which were members of NCI 's Community Clinical Oncology Program ( CCOP ) and were followed over 2 years . RESULTS A 2x2x19 analysis of variance was conducted with main effects of treatment condition , cohort , and baseline distress and their interactions . There was no main effect for treatment condition after removing one subject with an extreme score . Highly distressed women did not derive a greater benefit from treatment . Therapist training and psychotherapy experience were not associated with a treatment effect . CONCLUSIONS This study provides no evidence of reduction in distress as the result of a brief supportive-expressive intervention for women with primary breast cancer . Future studies might productively focus on women with higher initial levels of distress OBJECTIVE Psychosocial interventions are historically underutilized by cancer caregivers , but support programs delivered flexibly over the Internet address multiple barriers to care . We adapted Meaning-Centered Psychotherapy for cancer caregivers , an in-person psychotherapeutic intervention intended to augment caregivers ' sense of meaning and purpose and ameliorate burden , for delivery in a self-administered web-based program , the Care for the Cancer Caregiver ( CCC ) Workshop . The present study evaluated the feasibility , acceptability , and preliminary effects of this program . METHODS Eighty-four caregivers were r and omized to the CCC Workshop or waitlist control arm . Quantitative assessment s of meaning , burden , anxiety , depression , benefit finding , and spiritual well-being were conducted preintervention ( T1 ) , within 2-weeks postintervention ( T2 ) , and 2- to 3-month follow-up ( T3 ) . In-depth semistructured interviews were conducted with a subset of participants . RESULTS Forty-two caregivers were r and omized to the CCC Workshop . Attrition was moderate at T2 and T3 , with caregiver burden and bereavement as key causes of drop-out . At T2 and T3 , some observed mean change scores and effect sizes were consistent with hypothesized trends ( eg , meaning in caregiving , benefit finding , and depressive symptomatology ) , though no pre-post significant differences emerged between groups . However , a longitudinal mixed-effects model found significant differential increases in benefit finding in favor of the CCC arm . CONCLUSIONS The CCC Workshop was feasible and acceptable . Based on effect sizes reported here , a larger study will likely establish the efficacy of the CCC Workshop , which has the potential to address unmet needs of caregivers who underutilize in-person supportive care services CONTEXT Dignity therapy ( DT ) is a psychotherapeutic intervention with increasing evidence of acceptability and utility in palliative care setting s. OBJECTIVES The aim of this study was to evaluate the legacy creation component of DT by comparing this intervention with life review ( LR ) and waitlist control ( WC ) groups . METHODS Seventy adults with advanced terminal disease were r and omly allocated to DT , LR , or WC followed by DT , of which 56 completed the study protocol . LR followed an identical protocol to DT except that no legacy document was created in LR . Primary outcome measures were the Brief Generativity and Ego-Integrity Question naire , Patient Dignity Inventory , Functional Assessment of Cancer Therapy-General , version 4 , and treatment evaluation question naires . RESULTS Unlike LR and WC groups , DT recipients demonstrated significantly increased generativity and ego-integrity scores at study completion . There were no significant changes for dignity-related distress or physical , social , emotional , and functional well-being among the three groups . There were also no significant changes in primary outcomes after the provision of DT after the waiting period in the WC group . High acceptability and satisfaction with interventions were noted for recipients of both DT and LR and family/carers of DT participants . CONCLUSION This study provides initial evidence that the specific process of legacy creation is able to positively affect sense of generativity , meaning , and acceptance near end of life . High acceptability and satisfaction rates for both DT and LR and positive impacts on families/carers of DT participants provide additional support for clinical utility of these interventions . Further evaluation of specific mechanisms of change post-intervention is required given DT 's uncertain efficacy on other primary outcomes BACKGROUND The aim of this study was to assess the efficacy of meaning-centered group psychotherapy for cancer survivors ( MCGP-CS ) to improve personal meaning , compared with supportive group psychotherapy ( SGP ) and care as usual ( CAU ) . METHOD A total of 170 cancer survivors were r and omly assigned to one of the three study arms : MCGP-CS ( n = 57 ) ; SGP ( n = 56 ) ; CAU ( n = 57 ) . The primary outcome measure was the Personal Meaning Profile ( PMP ; total score ) . Secondary outcome measures were subscales of the PMP , psychological well-being ( Scales of Psychological Well-being ; SPWB ) , post-traumatic growth ( Posttraumatic Growth Inventory ) , Mental Adjustment to Cancer ( MAC ) , optimism ( Life Orientation Test-Revised ) , hopelessness ( Beck 's Hopelessness Scale ) , psychological distress ( anxiety and depression , Hospital Anxiety and Depression Scale ; HADS ) and quality of life ( European Organization for Research and Treatment of Cancer Quality of Life Question naire ; EORTC QLQ-C30 ) . Outcome measures were assessed before r and omization , post-intervention , and after 3 and 6 months of follow-up ( FU ) . RESULTS Linear mixed model analyses ( intention-to-treat ) showed significant differences between MCGP-CS , SGP and CAU on the total PMP score , and on (sub)scales of the PMP , SPWB , MAC and HADS . Post-hoc analyses showed significantly stronger treatment effects of MCGP-CS compared with CAU on personal meaning ( d = 0.81 ) , goal -orientedness ( d = 1.07 ) , positive relations ( d = 0.59 ) , purpose in life ( d = 0.69 ) ; fighting spirit ( d = 0.61 ) ( post-intervention ) and helpless/hopeless ( d = -0.87 ) ( 3 months FU ) ; and distress ( d = -0.6 ) and depression ( d = -0.38 ) ( 6 months FU ) . Significantly stronger effects of MCGP-CS compared with SGP were found on personal growth ( d = 0.57 ) ( 3 months FU ) and environmental mastery ( d = 0.66 ) ( 6 months FU ) . CONCLUSIONS MCGP-CS is an effective intervention for cancer survivors to improve personal meaning , psychological well-being and mental adjustment to cancer in the short term , and to reduce psychological distress in the long run OBJECTIVE This pilot study aim ed to provide supportive evidence for the acceptability and usefulness of the Meaning-Making intervention ( MMi ) in patients newly diagnosed with Stage III or IV ovarian cancer , and to provide estimates of parameters needed to design a full-scale study . METHODS A r and omized controlled trial with 24 patients ( 12 experimental and 12 control ) was conducted . Existential well-being ( primary outcome ) , overall quality of life , distress , anxiety , depression and self-efficacy were measured . RESULTS Compared to the control group , patients in the experimental group had a better sense of meaning in life at one and three months post-intervention . CONCLUSION The MMi seems a promising intervention for advanced cancer patients , and a full r and omized controlled trial is warranted to further investigate its efficacy PURPOSE To compare the efficacy of the following two empirically supported group interventions to help distressed survivors of breast cancer cope : mindfulness-based cancer recovery ( MBCR ) and supportive-expressive group therapy ( SET ) . PATIENTS AND METHODS This multisite , r and omized controlled trial assigned 271 distressed survivors of stage I to III breast cancer to MBCR , SET , or a 1-day stress management control condition . MBCR focused on training in mindfulness meditation and gentle yoga , whereas SET focused on emotional expression and group support . Both intervention groups included 18 hours of professional contact . Measures were collected at baseline and after intervention by assessors blind to study condition . Primary outcome measures were mood and diurnal salivary cortisol slopes . Secondary outcomes were stress symptoms , quality of life , and social support . RESULTS Using linear mixed-effects models , in intent-to-treat analyses , cortisol slopes were maintained over time in both SET ( P = .002 ) and MBCR ( P = .011 ) groups relative to the control group , whose cortisol slopes became flatter . Women in MBCR improved more over time on stress symptoms compared with women in both the SET ( P = .009 ) and control ( P = .024 ) groups . Per- protocol analyses showed greater improvements in the MBCR group in quality of life compared with the control group ( P = .005 ) and in social support compared with the SET group ( P = .012 ) . CONCLUSION In the largest trial to date , MBCR was superior for improving stress levels , quality of life and social support [ CORRECTED ] for distressed survivors of breast cancer . Both SET and MBCR also result ed in more normative diurnal cortisol profiles than the control condition . The clinical implication s of this finding require further investigation OBJECTIVE We developed a specific cognitive-existential intervention to improve existential distress in nonmetastatic cancer patients . The present study reports the feasibility of implementing and evaluating this intervention , which involved 12 weekly sessions in both individual and group formats , and explores the efficacy of the intervention on existential and global quality of life ( QoL ) measures . METHOD Some 33 nonmetastatic cancer patients were r and omized between the group intervention , the individual intervention , and the usual condition of care . Evaluation of the intervention on the existential and global QoL of patients was performed using the existential well-being subscale and the global scale of the McGill Quality of Life ( MQoL ) Question naire . RESULTS All participants agreed that their participation in the program helped them deal with their illness and their personal life . Some 88.9 % of participants agreed that this program should be proposed for all cancer patients , and 94.5 % agreed that this intervention helped them to reflect on the meaning of their life . At post-intervention , both existential and psychological QoL improved in the group intervention versus usual care ( p = 0.086 and 0.077 , respectively ) . At the three-month follow-up , global and psychological QoL improved in the individual intervention versus usual care ( p = 0.056 and 0.047 , respectively ) . SIGNIFICANCE OF RESULTS This pilot study confirms the relevance of the intervention and the feasibility of the recruitment and r and omization processes . The data strongly suggest a potential efficacy of the intervention for existential and global quality of life , which will have to be confirmed in a larger study Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more CONTEXT There is a little information about effective psychotherapies to enhance the spiritual well-being of terminally ill cancer patients . OBJECTIVES The primary aim of the study was to examine the efficacy of a one-week Short-Term Life Review for the enhancement of spiritual well-being , using a r and omized controlled trial . The secondary aim was to assess the effect of this therapy on anxiety and depression , suffering , and elements of a good death . METHODS The subjects were 68 terminally ill cancer patients r and omly allocated to a Short-Term Life- Review interview group or a control group . The patients completed question naires pre- and post-treatment , including the meaning of life domain from the Functional Assessment of Chronic Illness Therapy-Spiritual ( FACIT-Sp ) scale , the Hospital Anxiety and Depression Scale ( HADS ) , a numeric scale for psychological suffering , and items from the Good Death Inventory ( Hope , Burden , Life Completion , and Preparation ) . RESULTS The FACIT-Sp , Hope , Life Completion , and Preparation scores in the intervention group showed significantly greater improvement compared with those of the control group ( FACIT-Sp , P<0.001 ; Hope , P<0.001 ; Life Completion , P<0.001 ; and Preparation , P<0.001 ) . HADS , Burden , and Suffering scores in the intervention group also had suggested greater alleviation of suffering compared with the control group ( HADS , P<0.001 ; Burden , P<0.007 ; Suffering , P<0.001 ) . CONCLUSION We conclude that the Short-Term Life Review is effective in improving the spiritual well-being of terminally ill cancer patients , and alleviating psychosocial distress and promoting a good death Main objective To assess the ability of dignity therapy to reduce distress in advanced cancer patients . Design A phase II open-label trial . Setting Two UK National Health Service trusts . Participants 45 adults with advanced cancer . Intervention Dignity therapy : a brief palliative care psychotherapy . Methods Participants were r and omly allocated to receive the intervention plus st and ard care or st and ard care only ( control group ) . Outcomes were collected at baseline and at 1- and 4-week follow-up . Main outcome measures The primary outcome was dignity-related distress ( Palliative Dignity Inventory ) . Secondary outcomes were hope , anxiety and depression , quality of life , palliative-related outcomes , and self-reported study benefits . Results 45/188 ( 24 % ) patients responded . 27/45 ( 60 % ) participants remained at 1-week and 20/45 ( 44 % ) at 4-week follow-up . Baseline levels of distress were low . Groups did not differ in dignity-related distress at any time . An effect on only one secondary outcome was found : the intervention group reported more hope than the control group at both follow-ups . Effect sizes were medium ( partial η2=0.20 and 0.15 ) and the difference was statistically significant at 1-week follow-up ( difference in adjusted means 2.55 ; 95 % CI −4.73 to 0.36 ; p=0.02 ) . The intervention group was more positive than the control group on all the self-reported benefits ratings . Effect sizes ( Cohen 's d ) ranged from 1.34 for feeling that dignity therapy had helped to 0.31 for increasing will to live . Conclusions The effects of dignity therapy on people with advanced cancer are encouraging . Further investigation is warranted focusing on distressed patients and those earlier in the palliative care trajectory . Trial register number IS RCT N29868352 OBJECTIVE Dignity therapy ( DT ) is a short-term psychotherapy developed for patients living with a life-limiting illness . Our aim was to determine the influence of DT on symptoms of depression and anxiety in people with a life-threatening disease with high level of distress , referred to an inpatient palliative care unit . METHOD This was an open-label r and omized controlled trial . Sixty terminally ill patients were r and omly assigned to one of two groups : intervention group ( DT+ st and ard palliative care [ SPC ] ) or control group ( SPC alone ) . The main outcomes were symptoms of depression and anxiety , measured with the Hospital Anxiety and Depression Scale , assessed at baseline , day 4 , day 15 , and day 30 of follow-up . RESULTS Of the 60 participants , 29 were r and omized to DT and 31 to SPC . Baseline characteristics were similar between the two groups . DT was associated with a significant decrease in depressive symptoms at day 4 and day 15 ( mean = -4.46 , 95 % CI , -6.91 - 2.02 , p = 0.001 ; mean= -3.96 , 95 % CI , -7.33 to -0.61 ; p = 0.022 , respectively ) , but not at day 30 ( mean = -3.33 , 95 % CI , -7.32 - 0.65 , p = 0.097 ) . DT was also associated with a significant decrease in anxiety symptoms at each follow-up ( mean= -3.96 , 95 % CI , -6.66 to -1.25 , p = 0.005 ; mean= -6.19 , 95 % CI , -10.49 to -1.88 , p = 0.006 ; mean = -5.07 , 95 % CI , -10.22 to -0.09 , p = 0.054 , respectively ) . SIGNIFICANCE OF RESULTS DT appears to have a short-term beneficial effect on the depression and anxiety symptoms that often accompany patients at the end of their lives . Future research with larger sample s compared with other treatments is needed to better underst and the potential benefits of this psychotherapy Background Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life , a substantial number of patients with advanced cancer do not receive psycho-oncological interventions tailored to their individual situation . Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care setting s , we aim to examine the efficacy of a brief , manualized individual psychotherapy for patients with advanced cancer : Managing Cancer and Living Meaningfully ( CALM ) . CALM aims to reduce depression and death anxiety , to strengthen communication with health care providers , and to enhance hope and meaning in life . We adapted the intervention for German cancer care setting s. Methods / Design We use a single-blinded r and omized-controlled trial design with two treatment conditions : intervention group ( IG , CALM ) and control group ( CG ) . Patients in the CG receive a usual non-manualized supportive psycho-oncological intervention ( SPI ) . Patients are r and omized between the IG and CG and assessed at baseline ( t0 ) , after three ( t1 ) and after 6 months ( t2 ) . We include patients with a malignant solid tumor who have tumor stages of III or IV ( UICC classification ) . Patients who are included in the study are at least 18 years old , speak German fluently , score greater than or equal to nine on the PHQ-9 or/ and greater than or equal to five on the Distress Thermometer . It is further necessary that there is no evidence of severe cognitive impairments . We measure depression , anxiety , distress , quality of life , demoralization , symptom distress , fatigue as well as spiritual well-being , posttraumatic growth and close relationship experiences using vali date d question naires . We hypothesize that patients in the IG will show a significantly lower level of depression 6 months after baseline compared to patients in the CG . We further hypothesize a significant reduction in anxiety and fatigue as well as significant improvements in psychological and spiritual well-being , meaning and post-traumatic growth in the IG compared to CG 6 months after baseline . Discussion Our study will contribute important statistical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients .Trial registration Clinical Trials.gov PURPOSE / OBJECTIVES To develop the Meaning of Life Intervention in response to the need for brief and meaning-focused interventions in palliative care and to establish potential effect sizes for future full-scale r and omized , controlled trials . DESIGN A r and omized , controlled trial conducted to pilot test the Meaning of Life Intervention . SETTING A 68-bed oncology inpatient ward in an urban acute general hospital in Hong Kong . SAMPLE 84 patients with advanced-stage cancer . Fifty-eight completed the study . METHODS Assessment s of outcome variables were conducted at baseline and one day and two weeks after the intervention . Patients were r and omly allocated to the intervention group or the control group . Repeated measures analysis of covariance were conducted to assess the impact of the Meaning of Life Intervention on participants ' quality of life . MAIN RESEARCH VARIABLES The primary outcome was quality of life and was measured by the Quality -of-Life Concerns in the End-of-Life ( QOLC-E ) question naire and with a single-item scale on global quality of life . The eight subscales of the QOLC-E served as secondary outcomes . FINDINGS Statistically significant main effects were noted for the group in the QOLC-E question naire total score , the single-item scale on global quality of life , and the existential distress subscale of the QOLC-E question naire . The effects represented a medium effect size . CONCLUSIONS The results of this pilot study show that the Meaning of Life Intervention can improve quality of life , particularly existential distress . IMPLICATION S FOR NURSING The Meaning of Life Intervention represents a potentially effective and efficient intervention that is feasible for implementation by nursing staff for patients with advanced-stage cancer in a palliative care setting Background Managing Cancer And Living Meaningfully ( CALM ) is a brief individual psychotherapy for patients with advanced cancer . In an intervention-only phase 2a trial , CALM showed promising results , leading to the present 2b pilot , which introduces procedures for r and omisation and improved rigour in preparation for a phase 3 r and omised controlled trial ( RCT ) . Aims To test trial methodology and assess feasibility of a confirmatory RCT . Design A parallel-arm RCT ( intervention vs usual care ) with 3 and 6-month follow-ups . Assessment of feasibility included rates of consent , r and omisation , attrition , intervention non-compliance and usual care contamination . Primary outcome : depressive symptoms ( Patient Health Question naire-9 ; PHQ-9 ) . Secondary outcomes : major depressive disorder ( MDD ) , generalised anxiety , death anxiety , spiritual well-being , attachment anxiety and avoidance , self-esteem , experiential avoidance , quality of life and post-traumatic growth . Bayesian conjugate analysis was used in this low-powered setting . Setting / participants 60 adult patients with advanced cancer from the Princess Margaret Cancer Centre . Results Rate of consent was 32 % , r and omisation 78 % , attrition 25 % , non-compliance 37 % and contamination 17 % . There was support for potential treatment effects on : PHQ-9 , OR=1.48 , 95 % Credible Interval ( CRI.95 ) ( 0.65 , 3.38 ) ; MDD , OR=1.56 , CRI.95 ( 0.50 , 4.84 ) ; attachment anxiety , OR=1.72 , CRI.95 ( 0.73 , 4.03 ) ; and attachment avoidance , OR=1.58 , CRI.95 ( 0.67 , 3.71 ) . There was no support for effects on the seven remaining secondary outcomes . Conclusions A phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40 , with greater attention to issues of compliance and contamination . Trial registration number NCT02353546 Existential issues often accompany a diagnosis of cancer and remain one aspect of psychosocial oncology care for which there is a need for focused , empirically tested interventions . This study examined the efficacy of a novel psychological intervention specifically design ed to address existential issues through the use of meaning-making coping strategies on psychological adjustment to cancer . Eighty-two breast or colorectal cancer patients were r and omly chosen to receive routine care ( control group ) or up to four sessions that explored the meaning of the emotional responses and cognitive appraisal s of each individual 's cancer experience within the context of past life events and future goals ( experimental group ) . This paper reports the results from 74 patients who completed and returned pre- and post-test measures for self-esteem , optimism , and self-efficacy . After controlling for baseline scores , the experimental group participants demonstrated significantly higher levels of self-esteem , optimism , and self-efficacy compared to the control group . The results are discussed in light of the theoretical and clinical implication s of meaning-making coping in the context of stress and illness OBJECTIVES Meaning-Centered Group Psychotherapy ( MCGP ) has been demonstrated to be an effective method for improving advanced cancer patients ' quality of life and reducing their depression , hopelessness , and desire for hastened death . To further underst and MCGP , this study examined the mechanisms of change in MCGP on these outcomes via advanced cancer patients ' changes of sense of meaning and peace in life . METHODS The sample data were from 2 r and omized control trials that compared MCGP ( n = 124 ) to supportive group psychotherapy ( n = 94 ) . Mediation effects of treatment status on outcomes ( 2 months after completion of treatment ) via patients ' change in sense of meaning and peace ( posttreatment minus pretreatment ) were tested . The outcome variables used in these analyses were quality of life , depression , hopelessness , and desire for hastened death . RESULTS Significant mediation effects via change in sense of meaning and peace on these outcomes were found . Consistent results were found using intention-to-treated statuses . Weaker , but still significant , mediation effects via change in sense of faith on these outcomes were also found . CONCLUSIONS Results supported the hypotheses that improvement due to MCGP is mediated by advanced cancer patients ' enhanced sense of meaning . These findings highlight the importance of interventions focused on enhancing sense of meaning , as this appears to be a viable route to improve quality of life and decrease psychological distress among patients with advanced cancer The overall purpose of this study was to evaluate the effectiveness of a psychosocial supportive intervention called the " Living with Hope Program " ( LWHP ) in increasing hope and quality of life for older adult , community-living , terminally ill cancer patients . Using a mixed method concurrent nested experimental design , 60 terminally ill cancer patients over the age of 60 years were r and omly assigned to a treatment group and a control group . Baseline hope ( Herth Hope Index [ HHI ] ) and quality -of-life scores ( McGill Quality of Life Question naire [ MQOL ] ) were collected at the first visit in the patients ' homes by trained research assistants . Those in the treatment group received the LWHP , which consisted of viewing an international award-winning video on hope and a choice of one of three hope activities to work on over a one-week period . The control group received st and ard care . Hope and quality -of-life data were collected one week later from both groups . Qualitative data using open-ended hope questions were collected from the treatment group . Patients receiving the LWHP had statistically significant higher hope ( U=255 , P=0.005 ) and quality -of-life scores at Visit 2 ( U=294.5 , P=0.027 ) than those in the control group . Qualitative data confirmed this finding , with the majority ( 61.5 % ) of patients in the treatment group reporting the LWHP increased their hope . This preliminary evaluation of the effectiveness of the LWHP suggests that it may increase hope and quality of life for older terminally ill cancer patients at home OBJECTIVES An increasingly important concern for clinicians who care for patients at the end of life is their spiritual well-being and sense of meaning and purpose in life . In response to the need for short-term interventions to address spiritual well-being , we developed Meaning Centered Group Psychotherapy ( MCGP ) to help patients with advanced cancer sustain or enhance a sense of meaning , peace and purpose in their lives , even as they approach the end of life . METHODS Patients with advanced ( stage III or IV ) solid tumor cancers ( N=90 ) were r and omly assigned to either MCGP or a supportive group psychotherapy ( SGP ) . Patients were assessed before and after completing the 8-week intervention , and again 2 months after completion . Outcome assessment included measures of spiritual well-being , meaning , hopelessness , desire for death , optimism/pessimism , anxiety , depression and overall quality of life . RESULTS MCGP result ed in significantly greater improvements in spiritual well-being and a sense of meaning . Treatment gains were even more substantial ( based on effect size estimates ) at the second follow-up assessment . Improvements in anxiety and desire for death were also significant ( and increased over time ) . There was no significant improvement on any of these variables for patients participating in SGP . CONCLUSIONS MCGP appears to be a potentially beneficial intervention for patients ' emotional and spiritual suffering at the end of life . Further research , with larger sample s , is clearly needed to better underst and the potential benefits of this novel intervention Enhancing hope in people with a first recurrence of cancer Research ers and clinicians have identified the need for well-defined intervention studies to test the efficacy of interventions design ed to strengthen hope . This quasi-experimental study sought to determine if a specific nursing intervention program design ed to enhance hope would positively influence levels of hope and quality -of-life ( QOL ) in a convenience sample of 115 people with a first recurrence of cancer who were r and omly assigned to one of three groups : treatment group ( hope ) , attention control group ( informational ) , or control group ( usual treatment ) . The Herth Hope Index ( HHI ) and the Cancer Rehabilitation and Evaluation Systems , Short Form ( CARES-SF ) were administered prior to intervention , immediately after intervention and at 3 , 6 , and 9-month intervals . Treatment and control groups differed significantly with regard to level of hope ( P=0.02 ) and QOL ( P=0.03 ) . Both the level of hope and QOL were significantly increased ( P=0.03 ) immediately after intervention and across time ( 3 , 6 and 9 months ) . This study was a preliminary attempt to design , implement , and evaluate a theory-driven hope intervention program . Knowledge about the effectiveness of specific interventions design ed to enhance hope is vital if nurses are to significantly influence hope in those whom are in their care Background : Depression is poorly detected and sub-optimally managed in palliative care patients , and few trials of psychosocial interventions have been carried out in this group of patients . Aims : A pilot trial to determine the effect of a focused narrative intervention on depression in palliative care patients when used in addition to usual care . Design : Patients scoring 10 or higher on Patient Health Question naire-9 r and omised to focused narrative intervention in addition to usual care or usual care only and followed up at 2 , 4 and 6 weeks . A reduction of five points on Patient Health Question naire-9 was regarded as clinical ly significant response to treatment . Setting / participants : Palliative care patients aged over 18 recruited from hospice day care services – exclusion criteria included an estimated prognosis of 6 weeks or less , cognitive impairment and unable to underst and written or spoken English . Results : Out of 57 participating patients ( 71 % female ) , with mean age 65.1 years ( range 36–88 years ) , 33 patients were r and omised to the intervention and 24 to usual care only . Mean Patient Health Question naire-9 score at baseline was 16.4 . Patients receiving intervention had greater reduction in Patient Health Question naire-9 score at 6-week follow-up ( p = 0.04 ) . Median survival was 157 days for intervention and 102 days for control group patients ( p = 0.07 ) . Conclusion : This pilot trial suggests a focused narrative intervention in palliative care patients with moderate to severe depression can reduce depression scores more than usual care alone . Patients receiving intervention appeared to have longer survival . These results support the need for a fully powered trial BACKGROUND Dignity therapy is a unique , individualised , short-term psychotherapy that was developed for patients ( and their families ) living with life-threatening or life-limiting illness . We investigated whether dignity therapy could mitigate distress or bolster the experience in patients nearing the end of their lives . METHODS Patients ( aged ≥18 years ) with a terminal prognosis ( life expectancy ≤6 months ) who were receiving palliative care in a hospital or community setting ( hospice or home ) in Canada , USA , and Australia were r and omly assigned to dignity therapy , client-centred care , or st and ard palliative care in a 1:1:1 ratio . R and omisation was by use of a computer-generated table of r and om numbers in blocks of 30 . Allocation concealment was by use of opaque sealed envelopes . The primary outcomes --reductions in various dimensions of distress before and after completion of the study --were measured with the Functional Assessment of Chronic Illness Therapy Spiritual Well-Being Scale , Patient Dignity Inventory , Hospital Anxiety and Depression Scale , items from the Structured Interview for Symptoms and Concerns , Quality of Life Scale , and modified Edmonton Symptom Assessment Scale . Secondary outcomes of self-reported end-of-life experiences were assessed in a survey that was undertaken after the completion of the study . Outcomes were assessed by research staff with whom the participant had no previous contact to avoid any possible response bias or contamination . Analyses were done on all patients with available data at baseline and at the end of the study intervention . This study is registered with Clinical Trials.gov , number NCT00133965 . FINDINGS 165 of 441 patients were assigned to dignity therapy , 140 st and ard palliative care , and 136 client-centred care . 108 , 111 , and 107 patients , respectively , were analysed . No significant differences were noted in the distress levels before and after completion of the study in the three groups . For the secondary outcomes , patients reported that dignity therapy was significantly more likely than the other two interventions to have been helpful ( χ(2)=35·50 , df=2 ; p<0·0001 ) , improve quality of life ( χ(2)=14·52 ; p=0·001 ) , increase sense of dignity ( χ(2)=12·66 ; p=0·002 ) , change how their family saw and appreciated them ( χ(2)=33·81 ; p<0·0001 ) , and be helpful to their family ( χ(2)=33·86 ; p<0·0001 ) . Dignity therapy was significantly better than client-centred care in improving spiritual wellbeing ( χ(2)=10·35 ; p=0·006 ) , and was significantly better than st and ard palliative care in terms of lessening sadness or depression ( χ(2)=9·38 ; p=0·009 ) ; significantly more patients who had received dignity therapy reported that the study group had been satisfactory , compared with those who received st and ard palliative care ( χ(2)=29·58 ; p<0·0001 ) . INTERPRETATION Although the ability of dignity therapy to mitigate outright distress , such as depression , desire for death or suicidality , has yet to be proven , its benefits in terms of self-reported end-of-life experiences support its clinical application for patients nearing death . FUNDING National Cancer Institute , National Institutes of Health The aim of this study was to evaluate the effect of nursing intervention on hope and quality of life in cancer patients . The sample consisted of 96 newly diagnosed Norwegian cancer patients ages 26 to 78 years , the majority of them women ( 71 % ) . Breast cancer was the predominant type of cancer in this sample . The study used an experimental design in which patients were r and omly allocated to three different groups . The first group was the experimental group , for which the intervention was design ed to increase hope . The second group ( attention control group ) participated in the " Learning to Live with Cancer " program . The last group was a control group . The Nowotny Hope Scale was used to measure hope , and the Ferrans and Powers Quality of Life Index and the Cancer Rehabilitation and Evaluation Systems , short form , were used to measure quality of life . The question naires were completed four times : twice before , then 2 weeks and finally 6 months after the intervention . The level of hope was significantly increased ( p = 0.020 ) for the members of the hope group just after the intervention , but not after 6 months . Despite the patients ' positive evaluation of the intervention , there was no impact on quality of life PURPOSE To test the efficacy of meaning-centered group psychotherapy ( MCGP ) to reduce psychological distress and improve spiritual well-being in patients with advanced or terminal cancer . PATIENTS AND METHODS Patients with advanced cancer ( N = 253 ) were r and omly assigned to manualized eight-session interventions of either MCGP or supportive group psychotherapy ( SGP ) . Patients were assessed before and after completing the treatment and 2 months after treatment . The primary outcome measures were spiritual well-being and overall quality of life , with secondary outcome measures assessing depression , hopelessness , desire for hastened death , anxiety , and physical symptom distress . RESULTS Hierarchical linear models that included a priori covariates and only participants who attended ≥ three sessions indicated a significant group × time interaction for most outcome variables . Specifically , patients receiving MCGP showed significantly greater improvement in spiritual well-being and quality of life and significantly greater reductions in depression , hopelessness , desire for hastened death , and physical symptom distress compared with those receiving SGP . No group differences were observed for changes in anxiety . Analyses that included all patients , regardless of whether they attended any treatment sessions ( ie , intent-to-treat analyses ) , and no covariates still showed significant treatment effects ( ie , greater benefit for patients receiving MCGP v SGP ) for quality of life , depression , and hopelessness but not for other outcome variables . CONCLUSION This large r and omized controlled study provides strong support for the efficacy of MCGP as a treatment for psychological and existential or spiritual distress in patients with advanced cancer BACKGROUND Mindfulness-based cancer recovery ( MBCR ) and supportive expressive group therapy ( SET ) are two well-vali date d psychosocial interventions , but they have not been directly compared , and little is known about long-term outcomes . This comparative effectiveness study measured the effects of these two interventions immediately following the groups and for 1 year thereafter in distressed breast cancer survivors . METHODS Two hundred fifty-two distressed Stage I-III breast cancer survivors were r and omized into either MBCR or SET . Women completed question naires addressing mood , stress symptoms , quality of life , social support , spirituality and post-traumatic growth before and after the interventions , and 6 and 12 months later . RESULTS Immediately following the intervention , women in MBCR reported greater reduction in mood disturbance ( primarily fatigue , anxiety and confusion ) and stress symptoms including tension , sympathetic arousal and cognitive symptoms than those in SET . They also reported increased emotional and functional quality of life , emotional , affective and positive social support , spirituality ( feelings of peace and meaning in life ) and post-traumatic growth ( appreciation for life and ability to see new possibilities ) relative to those in SET , who also improved to a lesser degree on many outcomes . Effect sizes of the time × group interactions were small to medium , and most benefits were maintained over 12 months of follow-up . CONCLUSIONS This study is the first and largest to demonstrate sustained benefits of MBCR in distressed breast cancer survivors relative to an active control . MBCR was superior to SET for improving psychological well-being with lasting benefits over 1 year , suggesting these women gained long-lasting and efficacious tools to cope with cancer . TRIAL REGISTRATION Registered on clinical trials.gov number NCT00390169 , October 2006 . Copyright © 2016 John Wiley & Sons , Purpose Individuals with advanced cancer experience substantial distress in response to disease burden and impending mortality . Managing Cancer And Living Meaningfully ( CALM ) is a novel , brief , manualized psychotherapeutic intervention intended to treat and prevent depression and end-of-life distress in patients with advanced cancer . We conducted a r and omized controlled trial to compare CALM with usual care ( UC ) in this population . Methods Patients with advanced cancer were recruited from outpatient oncology clinics at a comprehensive cancer center into an unblinded r and omized controlled trial . Permuted block r and omization stratified by Patient Health Question naire-9 depression score allocated participants to CALM plus UC or to UC alone . Assessment s of depressive symptoms ( primary outcome ) , death-related distress , and other secondary outcomes were conducted at baseline , 3 months ( primary end point ) , and 6 months ( trial end point ) . Analyses were by intention to treat . Analysis of covariance was used to test for outcome differences between groups at follow-up , controlling for baseline . Mixed-model results are reported . Results Participants ( n = 305 ) were recruited between February 3 , 2012 , and March 4 , 2016 , and r and omly assigned to CALM ( n = 151 ) or UC ( n = 154 ) . CALM participants reported less-severe depressive symptoms than UC participants at 3 months ( Δ = 1.09 ; P = .04 ; Cohen ’s d = 0.23 ; 95 % CI , 0.04 to 2.13 ) and at 6 months ( Δ = 1.29 ; P = .02 ; d = 0.29 ; 95 % CI , 0.24 to 2.35 ) . Significant findings for greater end-of-life preparation at 6 months also favored CALM versus UC . No adverse effects were identified . Conclusion Findings suggest that CALM is an effective intervention that provides a systematic approach to alleviating depressive symptoms in patients with advanced cancer and addresses the predictable challenges these patients face Social and psychological interventions are often complex . Underst and ing r and omised controlled trials ( RCTs ) of these complex interventions requires a detailed description of the interventions tested and the methods used to evaluate them . However , RCT reports often omit , or inadequately report , this information . Incomplete and inaccurate reporting hinders the optimal use of research , wastes re sources and fails to meet ethical obligations to research participants and consumers . In this paper , we explain how reporting guidelines have improved the quality of reports in medicine , and describe the ongoing development of a new reporting guideline for RCTs : CONSORT-SPI ( an extension for social and psychological interventions ) . We invite readers to participate in the project by visiting our website , in order to help us reach the best-informed consensus on these guidelines ( http://tinyurl.com/CONSORT- study ) INTRODUCTION A pilot trial was carried out to determine if a focussed narrative interview could alleviate the components of suffering and anxiety and depression in advanced cancer patients . INTERVENTION Patients recruited were invited to participate in a focussed narrative interview and reflect on their perspectives on their sense of " meaning " , regarding suffering and their psychological , physical , social and spiritual well being - the emphasis was on allowing the patient to tell their story . Patients were encouraged to share what re sources they themselves had utilised in addition to what professional care they may have received , to maintain a sense of well being . METHOD Patients with advanced metastatic disease were recruited from hospices in the North West of Engl and - the only exclusion criteria were not being able to underst and written and spoken English and a non cancer diagnosis . At recruitment patients were asked to complete a numerical scale for suffering ; the Brief Edinburgh Depression Scale , Edmonton Symptom Assessment Scale ( ESAS ) , FACIT Spiritual well being question naire , Demographic information was collected and patients were r and omised to either the intervention arm of the trial or the usual care arm of the study . Patients in both groups were invited to complete each measure at 2 , 4 and 8 weeks . RESULTS One hundred people were recruited into the study - 49 were r and omised to intervention group and 51 to control group . The median age of patients was 66 years age range ( 31 - 89 years ) and 68 % of patients were female . At baseline the ECOG performance of 75 % of patients recruited was 1 or 2 . The median survival of all patients in the study was 169.5 days ( range 10 days to still alive at end of study ) . There was no significant difference at any timepoint in scores on suffering measure between intervention group and control group . At each time point the intervention demonstrated mean improvement in scores for depression and anxiety on ESAS - the greatest changes for both depression and anxiety were seen at 4 weeks . CONCLUSION This pilot r and omised controlled trial of a focussed narrative intervention demonstrated an improvement in mean changes in scores for depression and anxiety at 2 , 4 , and 8 weeks . We suggest this intervention may have beneficial effects on depression and anxiety , but a larger powered trial is required to determine the full effects BACKGROUND Empirical data suggest that life review is an effective psychospiritual intervention . However , it has not been applied to Chinese patients with advanced cancer , and its effects on this population remain unknown . OBJECTIVE The aim of the study was to determine the effect of a life review program on quality of life among Chinese patients with advanced cancer . METHODS In this prospect i ve r and omized controlled trial , a total of 80 patients were r and omly assigned to the life review program group and the control group . The 3-weekly life review program included review ing a life and formulating a life review booklet . Outcome data were assessed by a collector who was blinded to group assignment before and immediately after the program and at a 3-week follow-up . RESULTS Significantly better scores in overall quality of life , support , negative emotions , sense of alienation , existential distress , and value of life were found in the life review group immediately after the program and at the 3-week follow-up . CONCLUSION This study provides additional data on the potential role of a life review in improving quality of life , particularly psychospiritual well being ; it also indicates that the life review program could enable Chinese patients with advanced cancer to express their views on life and death . IMPLICATION S FOR PRACTICE The life review program offers advanced cancer patients an opportunity to integrate their whole life experiences and discuss end-of-life issues , which lays the ground for further active intervention in their psychospiritual distress . The program could be integrated into daily home care to enhance the psychospiritual well-being of Chinese patients with advanced cancer PURPOSE Evaluation of the effect of supportive expressive discussion groups on loneliness , hope and quality of life in breast cancer survivors . METHODS A r and omized control trial including breast cancer patients who had completed chemotherapy and r and omly allocated into two groups : intervention ( n = 41 ) and control ( n = 40 ) . The intervention consisted of twelve weekly 90-min sessions for groups of six to eight breast cancer survivors . Data were obtained pre-to -post the intervention and at 8-week follow-up . The data were analyzed using a repeated- measures analysis of variance ( ANOVA ) . RESULTS The findings revealed a significant reduction in loneliness scores ( F = 69.85 , p < 0.001 ) , promotion in total hope ( F = 20.8 , p < 0.05 ) and enhancement in quality of life from pre- to post-intervention , and then over the 8-week follow-up period in the intervention group , while scores of control participants did not show this pattern during the study . The strongest effects were found for global quality of life ( effect size ) = 0.59 ) , for future perspectives ( effect size = 0.51 ) , emotional functioning ( effect size = 0.35 ) and social functioning ( effect size = 0.31 ) . CONCLUSION The intervention was effective on loneliness , hope and quality of life in the intervention group . The intervention needs further evaluation in a larger study and with other cancer types . Copyright © 2016 John Wiley & Sons , PURPOSE To provide the 4-week prevalence estimates of mental disorders in cancer population s. PATIENTS AND METHODS We enrolled adult patients with cancer from in- and outpatient care facilities , using a proportional stratified r and om sample based on the nationwide cancer incidence in Germany . Patients who scored 9 or above on the Patient Health Question naire ( PHQ-9 ) were administered to the st and ardized computer-assisted Composite International Diagnostic Interview for mental disorders adapted for cancer patients ( CIDI-O ) . A r and om sample of those with a PHQ-9 score that was less than 9 were selected for a CIDI-O. RESULTS A total of 5,889 patients were identified , which led to 4,020 participants ( a 68.3 % response rate ) ; of those , 2,141 patients were interviewed . The 4-week total prevalence for any mental disorder was 31.8 % ( 95 % CI , 29.8 % to 33.8 % ) ; this included any anxiety disorder ( 11.5 % ; 95 % CI , 10.2 % to 12.9 % ) , any adjustment disorder ( 11.1 % ; 95 % CI , 9.7 % to 12.4 % ) , any mood disorder ( 6.5 % ; 95 % CI , 5.5 % to 7.5 % ) , any somatoform/conversion disorder ( 5.3 % ; 95 % CI , 4.3 % to 6.2 % ) , nicotine dependence ( 4.5 % ; 95 % CI , 3.6 % to 5.4 % ) , alcohol abuse/dependence ( 0.3 % ; 95 % CI , 0.1 % to 0.6 % ) , any mental disorder result ing from general medical condition ( 2.3 % ; 95 % CI , 1.7 % to 2.9 % ) , and any eating disorder ( 0 % ) . The highest prevalence for any mental disorder was found in patients with breast cancer ( 41.6 % ; 95 % CI , 36.8 % to 46.4 % ) , followed by patients with head and neck cancer ( 40.8 % ; 95 % CI , 28.5 % to 53.0 % ) . The lowest prevalence was found in patients with pancreatic cancer ( 20.3 % ; 95 % CI , 8.9 % to 31.6 % ) and stomach/esophagus cancers ( 21.2 % ; 95 % CI , 12.8 % to 29.6 % ) . CONCLUSION Our findings provide evidence for the strong need for psycho-oncological interventions |
12,840 | 30,481,531 | This analysis points to the existence of an unknown signalling mechanism accounting for approximately one third of the neurovascular response | HighlightsCellular and molecular mechanisms underlying increases in regional blood flow in response to neuronal activity are not fully understood .
We have compared the effects of 79 in vivo and 36 in vitro experimental attempts to inhibit the neurovascular response .
NA ; The mechanisms of neurovascular coupling contribute to ensuring brain energy supply is sufficient to meet dem and .
Despite significant research interest , the mechanisms underlying increases in regional blood flow that follow heightened neuronal activity are not completely understood .
This article presents a systematic review and analysis of published data reporting the effects of pharmacological or genetic blockade of all hypothesised signalling pathways of neurovascular coupling . | This study explored the possible use of caffeine as an agent to improve the BOLD ( blood oxygen level-dependent ) signal response in fMRI . Previous research has demonstrated that caffeine has the ability to reset the level of coupling between blood flow and neuronal activity . In the present study , it has been shown that caffeine causes a decrease in cerebral perfusion by as much as 13.2 % without a change in performance . Caffeine is a cerebral vasoconstrictor that causes an increase in the concentration of deoxyhemoglobin and thus a decrease in the BOLD baseline resting signal by 4.4 % . During activation , the vasculature responds from below-normal baseline levels with a normal increase in blood flow and volume , result ing in an overall increase in the BOLD contrast . This increase can be as large as 22 - 37 % during the performance of a visually cued motor task . The benefit of such a large increase in the BOLD contrast could be used to improve the image resolution , the acquisition scheme , or the task design of fMRI experiments . Caffeine has the potential to be used as a contrast booster for fMRI experiments The modulation of blood oxygenation level-dependent ( BOLD ) cerebral MRI contrast by the vasoconstrictive drug indomethacin ( i.v . 0.2 mg/kg b.w . ) was investigated in 10 healthy young adults without and with functional challenge ( repetitive and sustained visual activation ) . For comparison , isotonic saline ( placebo , 20 mL ) and acetylsalicylate ( i.v . 500 mg ) were investigated as well , each in separate sessions using identical protocol s. After indomethacin , dynamic T2 * -weighted echo-planar MRI at 2.0 T revealed a rapid decrease in MRI signal intensity by 2.1%-2.6 % in different gray matter regions ( P < or = 0.001 compared to placebo ) , which was not observed for acetylsalicylate and the placebo condition . Regional signal differences were not significant within gray matter , but all gray matter regions differed significantly from the signal decrease of only 1.2 % + /- 0.7 % observed in white matter ( P = 0.001 ) . For the experimental parameters used , a 1 % MRI signal decrease in response to indomethacin was estimated to correlate with a decrease of the cerebral blood flow by about 12 ml/100 g/minute , and an increase of the oxygen extraction fraction by about 15 % . Responses to visual activation were not affected by saline or acetylsalicylate , and yielded 5.0%-5.5 % BOLD MRI signal increases both before and after drug application . In contrast , indomethacin reduced the initial response strength to 82%-85 % of that obtained without the drug . The steady-state response during sustained activation reached only 47 % of the corresponding pre-drug level ( P < 0.01 ) . During repetitive activation the BOLD contrast was reduced to 66 % of that observed for control conditions ( P < 0.001 ) . In conclusion , indomethacin attenuates the vasodilatory force at functional brain activation , indicating different mechanisms governing neurovascular coupling KEY POINTS Cerebral blood flow increases during hypercapnia and decreases during hypocapnia ; it is unknown if vasomotion of the internal carotid artery is implicated in these responses . Indomethacin , a non-selective cyclooxygenase inhibitor ( used to inhibit prostagl and in synthesis ) , has a unique ability to blunt cerebrovascular carbon dioxide reactivity , while other cyclooxygenase inhibitors have no effect . We show significant dilatation and constriction of the internal carotid artery during hypercapnia and hypocapnia , respectively . Indomethacin , but not ketorolac or naproxen , reduced the dilatatory response of the internal carotid artery to hypercapnia The differential effect of indomethacin compared to ketorolac and naproxen suggests that indomethacin inhibits vasomotion of the internal carotid artery independent of prostagl and in synthesis inhibition . ABSTRACT Extra-cranial cerebral blood vessels are implicated in the regulation of cerebral blood flow during changes in arterial CO2 ; however , the mechanisms governing CO2 -mediated vasomotion of these vessels in humans remain unclear . We determined if cyclooxygenase inhibition with indomethacin ( INDO ) reduces the vasomotor response of the internal carotid artery ( ICA ) to changes in end-tidal CO2 ( P ETC O2 ) . Using a r and omized single-blinded placebo-controlled study , participants ( n = 10 ) were tested on two occasions , before and 90 min following oral INDO ( 1.2 mg kg(-1 ) ) or placebo . Concurrent measurements of beat-by-beat velocity , diameter and blood flow of the ICA were made at rest and during steady-state stages ( 4 min ) of iso-oxic hypercapnia ( + 3 , + 6 , + 9 mmHg P ETC O2 ) and hypocapnia ( -3 , -6 , -9 mmHg P ETC O2 ) . To examine if INDO affects ICA vasomotion independent of cyclooxygenase inhibition , two participant subsets ( each n = 5 ) were tested before and following oral ketorolac ( post 45 min , 0.25 mg kg(-1 ) ) or naproxen ( post 90 min , 4.2 mg kg(-1 ) ) . During pre-drug testing in the INDO trial , the ICA dilatated during hypercapnia at + 6 mmHg ( 4.72 ± 0.45 vs. 4.95 ± 0.51 mm ; P < 0.001 ) and + 9 mmHg ( 4.72 ± 0.45 mm vs. 5.12 ± 0.47 mm ; P < 0.001 ) , and constricted during hypocapnia at -6 mmHg ( 4.95 ± 0.33 vs. 4.88 ± 0.27 mm ; P < 0.05 ) and -9 mmHg ( 4.95 ± 0.33 vs. 4.82 ± 0.27 mm ; P < 0.001 ) . Following INDO , vasomotor responsiveness of the ICA to hypercapnia was reduced by 67 ± 28 % ( 0.045 ± 0.015 vs. 0.015 ± 0.012 mm mmHg P ETC O2(-1 ) ) . There was no effect of the drug in the ketorolac and naproxen trials . We conclude that : ( 1 ) INDO markedly reduces the vasomotor response of the ICA to changes in P ETC O2 ; and ( 2 ) INDO may be reducing CO2 -mediated vasomotion via a mechanism(s ) independent of cyclooxygenase inhibition Nitric oxide ( NO ) regulates basal CBF . In a number of animal models NO has been implicated in the mediation of the regional changes in CBF ( rCBF ) that accompany neuronal activation ( vasoneuronal coupling ) . However , some results in animal models have failed to confirm this finding , and the validity of extrapolation to man from animal data is uncertain . To determine the contribution of NO to basal global CBF and activation-induced changes in rCBF , the authors have performed quantitative H215O positron emission tomography ( PET ) studies before and after administration of the non-isoform-specific NO synthase inhibitor , NG-monomethyl-l-arginine ( L-NMMA ) , in 10 healthy male volunteers . Learning a novel sequence of finger movements was used as a paradigm to induce regional frontal cortex activation . The effect of NO synthase inhibition on the magnitude and pattern of activation was determined . Resting global CBF fell from 33.3 ± 5.3 mL·100 g−1·min−1 at rest before L-NMMA , to 26.5 ± 7.7 mL·100 g−1·min−1 after L-NMMA ( P = 0.001 ) . This fall was reversed by l-arginine administration . Learning sequential finger movements induced increases in rCBF in the left motor , right prefrontal , and bilateral premotor cortices . After NO synthase inhibition with L-NMMA , there was no change in this pattern of activation and no reduction in the magnitude of rCBF responses at the foci of maximal stimulation before and after L-NMMA . These findings confirm that NO production contributes to basal CBF regulation in man , but show that systemic NO synthase inhibition with L-NMMA does not impair regional vasoneuronal coupling |
12,841 | 31,419,968 | Discussion When WESW have access to more capital and /or alternative forms of employment and start earning formal income outside of sex work , they may be better able to improve their skills and employability for professional advancement , thereby reducing their STI/HIV risk . | Background Sub-Saharan Africa ( SSA ) has the highest number of people living with HIV/AIDS , with Nigeria , South Africa , and Ug and a accounting for 48 % of new infections .
A systematic review of the HIV burden among women engaged in sex work ( WESW ) in 50 low- and middle-income countries found that they had increased odds of HIV infection relative to the general female population .
Social structural factors , such as the sex work environment , violence , stigma , cultural issues , and criminalization of sex work are critical in shaping sexually transmitted infection (STI)/HIV risks among WESW and their clients in Ug and a. Poverty is the most commonly cited reason for involvement in sex work in SSA . | Background Violence against adolescent girls in humanitarian setting s is of urgent concern given their additional vulnerabilities to violence and unique health and well-being needs that have largely been overlooked by the humanitarian community . In order to underst and what works to prevent violence against adolescent girls , a multi-component curriculum-based safe spaces program ( Creating Opportunities through Mentorship , Parental involvement and Safe Spaces – COMPASS ) will be implemented and evaluated . The objectives of this multi-country study are to underst and the feasibility , acceptability and effectiveness of COMPASS programming to prevent violence against adolescent girls in diverse humanitarian setting s. Methods / design Two wait-listed cluster-r and omized controlled trials are being implemented in conflict-affected communities in eastern Democratic Republic of Congo ( N = 886 girls aged 10–14 years ) and in refugee camps in western Ethiopia ( N = 919 girls aged 13–19 years ) . The intervention consists of structured facilitated sessions delivered in safe spaces by young female mentors , caregiver discussion groups , capacity-building activities with service providers , and community engagement . In Ethiopia , the research centers on the overall impact of COMPASS compared to a wait-list group . In DRC , the research objective is to underst and the incremental effectiveness of the caregiver component in addition to the other COMPASS activities as compared to a wait-list group . The primary outcome is change in sexual violence . Secondary outcomes include decreased physical and emotional abuse , reduced early marriage , improved gender norms , and positive interpersonal relationships , among others . Qualitative method ologies seek to underst and girls ’ perceptions of safety within their communities , key challenges they face , and to identify potential pathways of change . Discussion These trials will add much needed evidence for the humanitarian community to meet the unique needs of adolescent girls and to promote their safety and well-being , as well as contributing to how multi-component empowerment programming for adolescent girls could be adapted across humanitarian setting s . Trial registration Clinical Trials NCT02384642 ( Registered : 2/24/15 ) & NCT02506543 ( Registered : 7/19/15 ) Women who exchange sex for money or other goods , that is , female sex workers , are at increased risk of experiencing physical and sexual violence from both paying and intimate partners . Exposure to violence can be exacerbated by alcohol use and HIV/STI risk . The purpose of this study is to examine the efficacy of a HIV/STI risk reduction and enhanced HIV/STI risk reduction intervention at decreasing paying and intimate partner violence against Mongolian women who exchange sex and engage in harmful alcohol use . Women are recruited and r and omized to either ( a ) four sessions of a relationship-based HIV/STI risk reduction intervention ( n = 49 ) , ( b ) the same HIV/STI risk reduction intervention plus two additional motivational interviewing sessions ( n = 58 ) , or ( c ) a four session control condition focused on wellness promotion ( n = 59 ) . All the respondents complete assessment s at baseline ( preintervention ) as well as at immediate posttest , 3 and 6 months postintervention . A multilevel logistic model finds that women who participated in the HIV/STI risk reduction group ( OR = 0.14 , p < .00 ) , HIV/STI risk reduction and motivational interview group ( OR = 0.46 , p = .02 ) , and wellness ( OR = 0.20 , p < .00 ) group reduced their exposure to physical and sexual violence in the past 90 days . No significant differences in effects are observed between conditions . This study demonstrates the efficacy of a relationship-based HIV/STI risk reduction intervention , a relationship-based HIV/STI risk reduction intervention combined with motivational interviewing , and a wellness promotion intervention in reducing intimate and paying partner violence against women who exchange sex in Mongolia . The findings have significant implication s for the impact of minimal intervention and the potential role of peer networks and social support in reducing women ’s experiences of violence in re source poor setting Objective : To assess effects of a combined microfinance and training intervention on HIV risk behavior among young female participants in rural South Africa . Design : Secondary analysis of quantitative and qualitative data from a cluster r and omized trial , the Intervention with Microfinance for AIDS and Gender Equity study . Methods : Eight villages were pair-matched and r and omly allocated to receive the intervention . At baseline and after 2 years , HIV risk behavior was assessed among female participants aged 14–35 years . Their responses were compared with women of the same age and poverty group from control villages . Intervention effects were calculated using adjusted risk ratios employing village level summaries . Qualitative data collected during the study explored participants ' responses to the intervention including HIV risk behavior . Results : After 2 years of follow-up , when compared with controls , young participants had higher levels of HIV-related communication ( adjusted risk ratio 1.46 , 95 % confidence interval 1.01–2.12 ) , were more likely to have accessed voluntary counseling and testing ( adjusted risk ratio 1.64 , 95 % confidence interval 1.06–2.56 ) , and less likely to have had unprotected sex at last intercourse with a nonspousal partner ( adjusted risk ratio 0.76 , 95 % confidence interval 0.60–0.96 ) . Qualitative data suggest a greater acceptance of intrahousehold communication about HIV and sexuality . Although women noted challenges associated with acceptance of condoms by men , increased confidence and skills associated with participation in the intervention supported their introduction in sexual relationships . Conclusions : In addition to impacts on economic well being , women 's empowerment and intimate partner violence , interventions addressing the economic and social vulnerability of women may contribute to reductions in HIV risk behavior Adolescents and young adults in sub-Saharan Africa ( SSA ) are particularly vulnerable to human immunodeficiency virus ( HIV ) and acquired immune deficiency syndrome ( AIDS ) infection . Adolescents orphaned as a direct result of HIV/AIDS are at an elevated risk of acquiring HIV/AIDS and other sexually transmitted infections . However , limited empirical evidence exists on HIV knowledge and prevention programs , especially those design ed to address HIV information gaps among adolescents . This study evaluates the effect of a peer mentorship program provided in addition to other supportive services on HIV/AIDS knowledge , beliefs , and prevention attitudes , among school-going orphaned adolescents in southern Ug and a. We utilize data from the Bridges to the Future Study , a 5-year longitudinal r and omized experimental study funded by the National Institute of Child Health and Human Development . Out of the 1410 adolescents enrolled in the study ( average age = 12.7 at study initiation ) , 855 of them participated in a nine-session , curriculum based peer mentorship program . We analyzed data collected at baseline and 12-months post intervention initiation . The results from bivariate and regression analysis indicate that , controlling for socioeconomic characteristics , adolescents who participated in a peer mentorship program were more likely than non- participants to report increased scores on HIV/AIDS knowledge ; better scores on desired HIV/AIDS-related beliefs ; and better scores on HIV/AIDS prevention attitudes . Overall , the study findings point to the potential role of a peer mentorship program in promoting the much-desired HIV/AIDS knowledge , beliefs , and prevention attitudes among orphaned adolescents . Future programs and policies that support AIDS-orphaned adolescents in sub-Saharan Africa should consider incorporating peer mentoring programs that provide correct , age , and culturally appropriate HIV information to help protect orphaned adolescents and reduce the risk of HIV infections Background “ Let Us Protect Our Future ” is a sexual risk-reduction intervention for sixth- grade adolescents in South Africa . Tested in a cluster-r and omized controlled trial , the intervention significantly reduced self-reported intercourse and unprotected intercourse during a 12-month follow-up period . Purpose The present analyses were conducted to identify moderators of the intervention ’s efficacy as well as , which theory-based variables mediated the intervention ’s effects . Methods Intervention efficacy over the 3- , 6- , and 12-month follow-up was tested using generalized estimating equation models . Results Living with their father in the home , parental strictness , and religiosity moderated the efficacy of the intervention in reducing unprotected intercourse . Self-efficacy to avoid risky situations and expected parental disapproval of their having intercourse , derived from Social Cognitive Theory , significantly mediated the intervention ’s effect on abstinence . Conclusions This is the first study to demonstrate that Social Cognitive variables mediate the efficacy of a sexual risk-reduction intervention among South African adolescents Background Among women at high risk for HIV and other sexually transmitted diseases ( STIs ) , gender and economic issues limit the impact of behavioral prevention strategies . Women in Kazakhstan with dual risks of sex trading and drug use face elevated risk for HIV and STIs and may benefit from an economic empowerment intervention which combines HIV-risk reduction ( HIVRR ) education with financial skills-building and asset-building to promote reduced reliance on sex trading for income . Methods / design The study employs a two-arm , cluster-r and omized controlled trial ( c- RCT ) design . We will use cluster r and omization to assign 350 women in approximately 50 cohorts to a traditional four-session HIV-risk-reduction intervention combined with a six-session financial literacy intervention , enrollment in a 24-session vocational training program and receipt of matched savings ( HIVRR+MF ) ; or to the four-session HIV-risk-reduction intervention alone ( HIVRR ) . Repeated behavioral and biological assessment s will be conducted at baseline , then at 6 , 9 , and 15 months post r and omization/session 1 . Discussion This study responds to an identified need in the academic literature for rigorous testing of structural interventions , including combination microfinance and HIV-prevention interventions .Trial registration Clinical Trials.gov , ID : NCT02406482 . Registered on 30 March 2015 Children comprise the largest proportion of the population in sub-Saharan Africa . Of these , millions are orphaned . Orphanhood increases the likelihood of growing up in poverty , dropping out of school , and becoming infected with HIV . Therefore , programs aim ed at securing a healthy developmental trajectory for these orphaned children are desperately needed . We conducted a two-arm cluster-r and omized controlled trial to evaluate the effectiveness of a family-level economic strengthening intervention with regard to school attendance , school grade s , and self-esteem in AIDS-orphaned adolescents aged 12–16 years from 10 public rural primary schools in southern Ug and a. Children were r and omly assigned to receive usual care ( counseling , school uniforms , school lunch , notebooks , and textbooks ) , “ bolstered ” with mentorship from a near-peer ( control condition , n = 167 ) , or to receive bolstered usual care plus a family-level economic strengthening intervention in the form of a matched Child Savings Account ( Suubi-Maka treatment arm , n = 179 ) . The two groups did not differ at baseline , but 24 months later , children in the Suubi-Maka treatment arm reported significantly better educational outcomes , lower levels of hopelessness , and higher levels of self-concept compared to participants in the control condition . Our study contributes to the ongoing debate on how to address the developmental impacts of the increasing numbers of orphaned and vulnerable children and adolescents in sub-Saharan Africa , especially those affected by HIV/AIDS . Our findings indicate that innovative family-level economic strengthening programs , over and above bolstered usual care that includes psychosocial interventions for young people , may have positive developmental impacts related to education , health , and psychosocial functioning This study examined the efficacy of an enhanced intervention to reduce sexual risk of HIV/STI and harmful alcohol use among female sex workers in Mongolia . Women ( n = 166 ) were recruited and r and omized to either ( 1 ) a relationship-based HIV sexual risk reduction intervention ; ( 2 ) the same sexual risk reduction intervention plus motivational interviewing ; or ( 3 ) a control condition focused on wellness promotion . At three and six month follow-up , both treatment interventions and the wellness promotion condition were effective in reducing the percentage and the number of unprotected acts of vaginal sex with paying partners in the past 90 days . All three conditions demonstrated efficacy in reducing harmful alcohol use . No significant differences in effects were observed between conditions . Findings suggest that even low impact behavioral interventions can achieve considerable reductions of HIV/STI risk and harmful alcohol use with a highly vulnerable population in a low re source d setting Background Some studies show orphanhood to be associated with increased sexual risk-taking while others have not established this relationship , but have found factors other than orphanhood as predictors of sexual risk behaviours and outcomes among adolescents . This study examines community members ’ perceptions of how poverty influences adolescent sexual behaviour and outcomes in four districts of Nyanza Province , Kenya . Methods Eight study sites within the four districts were r and omly selected . Focus group discussion s were conducted with a purposive sample of adolescents , parents and caregivers . Key informant interviews were undertaken with a purposive sample of community leaders , child welfare and healthcare workers , and adolescents . The two methods elicited information on factors perceived to predispose adolescent orphans and non-orphans to sexual risks . Data were analysed through line-by-line coding , grouped into families and retrieved as themes and sub-themes . Results Participants included 147 adolescents and parents/caregivers in 14 focus groups and 13 key informants . Poverty emerged as a key predisposing factor to sexual risk behaviour among orphans and non-orphans . Poverty was associated with lack of food , poor housing , school dropout , and engaging in income generating activities , all of which increase their vulnerability to transactional sex , early marriage , sexual experimentation , and the eventual consequences of increased risk of unintended pregnancies and STI/HIV . Conclusion Poverty was perceived to contribute to increasing sexual risks among orphan and non-orphan adolescents through survival strategies adopted to be able to meet their basic needs . Policies for prevention and intervention that target adolescents in a generalized poverty and HIV epidemic should integrate economic empowerment for caregivers and life skills for adolescents to reduce vulnerabilities of orphan and non-orphan adolescents to sexual risk behaviour OBJECTIVES This study examined the efficacy of a relationship-based HIV/sexually transmitted disease prevention program for heterosexual couples and whether it is more effective when delivered to the couple or to the woman alone . METHODS Couples ( n = 217 ) were recruited and r and omized to ( 1 ) 6 sessions provided to couples together ( n = 81 ) , ( 2 ) the same intervention provided to the woman alone ( n = 73 ) , or ( 3 ) a 1-session control condition provided to the woman alone ( n = 63 ) . RESULTS The intervention was effective in reducing the proportion of unprotected and increasing the proportion of protected sexual acts . No significant differences in effects were observed between couples receiving the intervention together and those in which the woman received it alone . CONCLUSIONS This study demonstrates the efficacy of a relationship-based prevention program for couples at risk for HIV infection PURPOSE This present study tests the proposition that an economic strengthening intervention for families caring for AIDS-orphaned adolescents would positively affect adolescent future orientation and psychosocial outcomes through increased asset accumulation ( in this case , by increasing family savings ) . METHODS Using longitudinal data from the cluster-r and omized experiment , we ran generalized estimating equation models with robust st and ard errors clustering on individual observations . To examine whether family savings mediate the effect of the intervention on adolescents ' future orientation and psychosocial outcomes , analyses were conducted in three steps : ( 1 ) testing the effect of intervention on mediator ; ( 2 ) testing the effect of mediator on outcomes , controlling for the intervention ; and ( 3 ) testing the significance of mediating effect using Sobel-Goodman method . Asymmetric confidence intervals for mediated effect were obtained through bootstrapping-to address the assumption of normal distribution . RESULTS Results indicate that participation in a matched Child Savings Account ( CSA ) program improved adolescents ' future orientation and psychosocial outcomes by reducing hopelessness , enhancing self-concept , and improving adolescents ' confidence about their educational plans . However , the positive intervention effect on adolescent future orientation and psychosocial outcomes was not transmitted through saving . In other words , participation in the matched CSA program improved adolescent future orientation and psychosocial outcomes regardless of its impact on reported savings . CONCLUSIONS Further research is necessary to underst and exactly how participation in economic strengthening interventions , for example , those that employ matched CSAs , shape adolescent future orientation and psychosocial outcomes : what , if not savings , transmits the treatment effect and how OBJECTIVES We examined the effect of economic assets on sexual risk-taking intentions among school-going AIDS-orphaned adolescents in rural Ug and a. METHODS AIDS-orphaned adolescents from 15 comparable schools were r and omly assigned to control ( n = 133 ) or treatment ( n = 127 ) conditions . Treatment participants received child savings accounts , workshops , and mentorship . This economic intervention was in addition to the traditional care and support services for school-going orphaned adolescents ( counseling and school supplies ) provided to both treatment and control groups . Adolescents in the treatment condition were compared with adolescents in the control condition at baseline and at 10 months after the intervention . RESULTS After control for sociodemographic factors , child-caregiver/parental communication , and peer pressure , adolescents in the economic intervention group reported a significant reduction in sexual risk-taking intentions compared with adolescents in the control condition . CONCLUSIONS The findings indicate that in Ug and a , a country devastated by poverty and disease ( including HIV/AIDS ) , having access to economic assets plays an important role in influencing adolescents ' sexual risk-taking intentions . These findings have implication s for the care and support of orphaned adolescents , especially in poor African countries devastated by poverty and sexually transmitted diseases OBJECTIVES This study evaluated an intervention design ed to improve behavioral and mental health outcomes among adolescents and their parents with AIDS . METHODS Parents with AIDS ( n = 307 ) and their adolescent children ( n = 412 ) were r and omly assigned to an intensive intervention or a st and ard care control condition . Ninety-five percent of subjects were reassessed at least once annually over 2 years . RESULTS Adolescents in the intensive intervention condition reported significantly lower levels of emotional distress , of multiple problem behaviors , of conduct problems , and of family-related stressors and higher levels of self-esteem than adolescents in the st and ard care condition . Parents with AIDS in the intervention condition also reported significantly lower levels of emotional distress and multiple problem behaviors . Coping style , levels of disclosure regarding serostatus , and formation of legal custody plans were similar across intervention conditions . CONCLUSIONS Interventions can reduce the long-term impact of parents ' HIV status on themselves and their children Summary Pneumocystis carinii pneumonia ( PCP ) is the most common severe opportunistic infection , and one of the most costly , among people with AIDS . Over 50 % of patients experience toxic effects of the major anti-PCP medications — cotrimoxazole ( trimethoprim-sulfamethoxazole ) and pentamidine . Recently , the US Food and Drug Administration approved a new oral drug therapy , atovaquone , as an alternative to pentamidine for the treatment of people with mild-to-moderate PCP who are intolerant of cotrimoxazole . We developed a decision tree model to estimate the costs and cost effectiveness of atovaquone therapy compared with intravenous pentamidine therapy for cotrimoxazole-intolerant patients with mild-to-moderate PCP . Clinical outcomes were based on data from a phase III trial comparing the 2 medications . Our economic outcomes were based on treatment algorithms derived from discharge data , published reports and the clinical judgement of the co- authors .We estimate the total expected cost of treating a patient for an episode of PCP with atovaquone to be SUS3990 compared with $ US6545 for pentamidine under our baseline scenario ( 1995 dollars ) . Our decision model also provides insight into the large cost-savings benefits of treating mild-to-moderate PCP on an outpatient basis Atrial fibrillation and atrial flutter are cardiac rhythm disorders that are often symptomatic and may interfere with the heart 's function , limiting its effectiveness . These arrhythmias are responsible for a large number of hospitalizations at a significant cost to the healthcare system . Electrical cardioversion ( EC ) is the most common nonpharmacologic intervention used to convert atrial fibrillation and atrial flutter to normal rhythm . Electrical cardioversion is highly successful in converting patients to normal rhythm ; however , it is more traumatic and re source intensive than pharmacologic treatment . Recently , a new rapid-acting drug , ibutilide , was approved for the conversion of atrial fibrillation and atrial flutter . Ibutilide is administered through intravenous infusion and does not require anesthetization of the patient , as is required for EC . A decision-tree model was developed to estimate the cost-effectiveness of ibutilide therapy compared with EC therapy . Clinical outcomes were based on a phase III trial of ibutilide , and re source use was based on the literature and physician clinical judgment . A stepped conversion regimen of first-line ibutilide followed by EC for patients who fail to convert is less expensive and has a higher conversion rate than first-line EC . Sensitivity analysis shows that our results are robust to changes in cost and effectiveness estimates This study tested an economic intervention to reduce HIV risks among AIDS-orphaned adolescents . Adolescents ( n = 96 ) were r and omly assigned to receive the intervention or usual care for orphans in Ug and a. Data obtained at baseline and 12-month follow-up revealed significant differences between the treatment and control groups in HIV prevention attitudes and educational planning Female sex workers have been central in India ’s HIV epidemic since it was first diagnosed among them in 1989 . Female sex workers ’ risk of HIV is primarily economically motivated . The Pi pilot study examined the feasibility and association of a microenterprise intervention , the tailoring of canvas bags , on sexual risk behaviors among female sex workers ( N = 100 ) in Chennai . Women were r and omized to an intervention or control arm . Between-group comparisons at baseline and at six-month follow-up were performed . Multivariate linear regression with bootstrapping was conducted to estimate the intervention effect . At baseline , women were a median of 35 years old , 61 % were married and they had an average of two children . Intervention participants reported a significantly lower number of sex partners and significant increases in income at the 6-month follow-up compared to control participants . In a multivariate model , intervention participants had a significantly lower number of paying clients per month at follow-up compared to control participants . By graduation , 75 % of intervention arm participants had made at least one sellable canvas bag and 6 months after the study ’s end , 60 % have continued involvement in bag production . The pilot study demonstrated that microenterprise interventions are successful in both providing FSWs with licit income opportunities and was associated with reductions in HIV risk behaviors This study evaluated an economic empowerment intervention design ed to promote life options , health and mental health functioning among AIDS-orphaned adolescents in rural Ug and a. The study used an experimental design in which adolescents ( N=267 ) were r and omly assigned to receive an economic empowerment intervention or usual care for orphaned children . The study measured mental health functioning using 20 items of the Tennessee Self-Concept Scale ( TSCS : 2)--a st and ardized measure for self-esteem- and measured overall health using a self-rated health measure . Data obtained at 10-month follow-up revealed significant positive effects of the economic empowerment intervention on adolescents ' self-rated health and mental health functioning . Additionally , health and mental health functioning were found to be positively associated with each other . The findings have implication s for public policy and health programming for AIDS-orphaned adolescents PURPOSE Prior studies demonstrated the effect of family-based economic empowerment intervention Suubi on reducing attitudes approving sexual risk-taking behavior among orphaned adolescents in Ug and a. To underst and mechanisms of change , the article examines the effect of Suubi intervention on family support variables and their role in mediating the change in adolescents ' attitudes toward sexual risk-taking . METHODS The Suubi study used a cluster-r and omized experimental design with three waves , and included 283 orphaned adolescents from 15 primary schools in Rakai , Ug and a. First , using mixed-effects models , the study tested for the effect of intervention on family support variables . Second , using mediation analysis , the study examined whether the change in sexual risk-taking attitudes was mediated by the change in family support . RESULTS Compared with adolescents from the control group , at wave 2 , adolescents in the treatment group reported higher levels of perceived support from caregivers , were more willing to talk to caregivers about their problems , and felt more comfortable talking about sexual risk behaviors with their caregivers . Mediation analysis demonstrated that the improvement in perceived support from caregivers at wave 2 accounted for 16.8 % of the reduction in adolescents ' attitudes toward sexual risk-taking behavior at wave 3 ( z = -2.21 , p < .05 ) . CONCLUSIONS A family-based economic empowerment intervention Suubi may have the potential to increase family support to orphaned adolescents . Interventions aim ed at strengthening existing social networks and improving connectedness with surviving family members may be critical in preventing sexual risk-taking behavior among orphaned adolescents in Ug and a , which is characterized by low re sources Objectives To examine HIV-1-related mortality and demographic impact in a high HIV prevalence rural district of Ug and a. Design One-year follow-up ( 1990–1991 ) in a population -based rural cohort . Setting and participants Annual enumeration of all consenting residents of 1945 households in 31 r and omly selected community clusters in Rakai District . Subjects provided yearly HIV serological sample s , behavioral and health information . Main outcome measureMortality in HIV-infected and uninfected persons . Results Mortality among HIV-seropositive adults aged ≥15 years of 118.4 per 1000 person-years ( PY ) was substantially higher than in HIV-seronegative adults [ 12.4 per 1000 PY ; relative risk ( RR ) , 9.5 ; 95 % confidence interval ( CD , 6.0–14.9 ] . Infant mortality among offspring of HIV-infected mothers was almost double that for uninfected women ( 210 compared with 111 per 1000 live births ; RR , 1.9 ; 95 % Cl , 1.0–3.5 ) . Adult HIV-related mortality was associated with HIV prevalence and , in this cohort , with higher education , non-agricultural occupation and residence in roadside trading centers . We estimate that adult HIV prevalence in the district is 13 % and adult HIV attributable mortality 52 % . For all ages combined , district HIV attributable mortality is 28 % . Conclusion HIV is the leading cause of adult death in Rakai . Its effects on mortality are particularly marked in the most economically active sectors . However , the overall crude birth rate in the district ( 45.7 per 1000 population ) remains higher than the crude death rate ( 28.1 per 1000 population ) , result ing in continued rapid population growth This study examines an economic empowerment model of care and support for orphaned adolescents in rural Ug and a. Under this model , 277 AIDS-orphaned youths ( ages 11 - 17 ) from 15 comparable schools were r and omly assigned to either the usual care , which involves provision of counseling and education-related supplies , or the experimental condition , in which participants also received matched-savings accounts . The analyses indicate that poor families in rural Ug and a can and do save for their youths if provided with support and incentives . Analyses also locate statistically significant differences between youths in the experimental and control groups on attitudes toward saving , academic performance , educational aspirations , and health-related behaviors . The results suggest that savings-related interventions have a place in the care and support of orphaned youths in poor sub-Saharan Africa , where the number of such youths is steadily increasing Objective The authors examine whether an innovative family economic empowerment intervention addresses mental health functioning of AIDS-affected children in communities heavily impacted by HIV/AIDS in Ug and a. Methods A cluster r and omised controlled trial consisting of two study arms , a treatment condition ( n=179 ) and a control condition ( n=118 ) , was used to examine the impact of the family economic empowerment intervention on children 's levels of hopelessness and depression . The intervention comprised matched children savings accounts , financial management workshops and mentorship . Data were collected at baseline and 12 months post-intervention . Results Using multivariate analysis with several socioeconomic controls , the authors find that children in the treatment condition ( receiving the intervention ) report significant improvement in their mental health functioning . Specifically , the intervention reduces hopelessness and depression levels . On the other h and , children in the control condition ( not receiving the intervention ) report no changes on both measures . Conclusions The findings indicate that children with poor mental health functioning living in communities affected by HIV/AIDS may benefit from innovative family economic empowerment interventions . As measures of mental health functioning , both hopelessness and depression have long-term negative psychosocial and developmental impacts on children . These findings have implication s for public health programmes intended for long-term care and support of children living in re source poor AIDS-impacted communities This study examines participants ' savings in children 's savings accounts ( CSAs ) set up for AIDS-orphaned children ages 10 - 15 in Ug and a. Using a cluster r and omized experimental design , we examine the extent to which families participating in a CSA program report more savings than their counterparts not participating in the program , explore the extent to which families who participate in the CSA program report using formal financial institutions compared with families who do not have a CSA , and consider whether families participating in the CSA program bring new money into the CSA or whether they reshuffle existing household assets . We find that participating in a CSA increased families ' likelihood to report having saved money . However , our results show no intervention effect either on the amount of self-reported savings or on the likelihood of using formal financial institutions . Further research is needed to underst and whether use of a CSA helps families generate new wealth PURPOSE By adversely affecting family functioning and stability , poverty constitutes an important risk factor for children 's poor mental health functioning . This study examines the impact of a comprehensive microfinance intervention , design ed to reduce the risk of poverty , on depression among AIDS-orphaned youth . METHODS Children from 15 comparable primary schools in Rakai District of Ug and a , one of those hardest hit by HIV/AIDS in the country , were r and omly assigned to control ( n = 148 ) or treatment ( n = 138 ) conditions . Children in the treatment condition received a comprehensive microfinance intervention comprising matched savings accounts , financial management workshops , and mentorship . This was in addition to traditional services provided for all school-going orphaned adolescents ( counseling and school supplies ) . Data were collected at wave 1 ( baseline ) , wave 2 ( 10 months after intervention ) , and wave 3 ( 20 months after intervention ) . We used multilevel growth models to examine the trajectory of depression in treatment and control conditions , measured using Children 's Depression Inventory ( Kovacs ) . RESULTS Children in the treatment group exhibited a significant decrease in depression , whereas their control group counterparts showed no change in depression . CONCLUSIONS The findings indicate that over and above traditional psychosocial approaches used to address mental health functioning among orphaned children in sub-Saharan Africa , incorporating poverty alleviation-focused approaches , such as this comprehensive microfinance intervention , has the potential to improve psychosocial functioning of these children This study examines variations in saving behavior among poor families enrolled in a Child Savings Account program for orphaned and vulnerable school-going children in Ug and a. We employ multilevel analyses using longitudinal data from a cluster-r and omized experimental design . Our analyses reveal the following significant results : ( 1 ) given the average number of months during which the account was open ( 18 months ) , families saved on average , USD 54.72 , which , after being matched by the program ( 2:1 match rate ) comes to USD 164.16—enough to cover approximately five academic terms of post- primary education ; ( 2 ) children ’s saving behavior was not associated with quality of family relations ; it was , however , significantly associated with family financial socialization ; ( 3 ) family demographics were significantly associated with children ’s saving behavior in the matched Child Savings Account program ; and ( 4 ) children enrolled in some schools saved better compared to children enrolled in other schools within the same treatment group BACKGROUND A community-r and omised trial was undertaken to assess the impact , cost , and cost-effectiveness of averting HIV-1 infection through improved management of sexually transmitted diseases ( STDs ) by primary -health-care workers in Mwanza Region , Tanzania . METHODS The impact of improved treatment services for STDs on HIV-1 incidence was assessed by comparison of six intervention communities with six matched communities . We followed up a r and om cohort of 12,537 adults aged 15 - 54 years for 2 years to record incidence of HIV-1 infection . The total and incremental costs of the intervention were estimated ( ingredients approach ) and used to calculate the total cost per case treated , the incremental cost per HIV-1 infection averted , and the incremental cost per disability-adjusted life-year ( DALY ) saved . FINDINGS During 2 years of follow-up , 11,632 cases of STDs were treated in the intervention health units . The baseline prevalence of HIV-1 infection was 4 % . The incidence of HIV-1 infection during the 2 years was 1.16 % in the intervention communities and 1.86 % in the comparison communities . An estimated 252 HIV-1 infections were averted each year . The total annual cost of the intervention was US$ 59,060 ( 1993 prices ) , equivalent to $ 0.39 per head of population served . The cost for STD case treated was $ 10.15 , of which the drug cost was $ 2.11 . The incremental annual cost of the intervention was $ 54,839 , equivalent to $ 217.62 per HIV-1 infection averted and $ 10.33 per DALY saved ( based on Tanzanian life expectancy ) or $ 9.45 per DALY saved ( based on the assumptions of the World Development Report ) . In a sensitivity analysis of factors influencing cost-effectiveness , cost per DALY saved ranged from $ 2.51 to $ 47.86 . INTERPRETATION Improved management of STDs in rural health units reduced the incidence of HIV-1 infection in the general population by about 40 % . The estimated cost-effectiveness of this intervention ( $ 10 per DALY ) compares favourably with that of , for example , childhood immunisation programmes ( $ 12 - 17 per DALY ) . Cost-effectiveness should be further improved when the intervention is applied on a larger scale . Re sources should be made available for this highly cost-effective HIV control strategy Measures of self-efficacy to use condoms can clarify the barriers to condom use Latinos encounter . A 20-item scale , that differed slightly for men and women , and was based on extensive elicitation interviews , was used in a r and om digit dial household survey of 1,600 unmarried Latino adults in 10 states with large Latino population s. Self-efficacy was related to condom use for both men and women . Factor analyses revealed five correlated factors : Regular Partner , Impulse Control , Partner Resistance , STD Thoughts , and Condom Discussion . Both men and women reported lowest self-efficacy for impulse control and using condoms with a regular partner . Less-educated men and women had lower self-efficacy to discuss condoms , to manage partner resistance , to use condoms with a regular partner , and to control impulses , but there were few other demographic differences in self-efficacy . The scale can be helpful in the design and evaluation of HIV prevention To assess the effect of a savings-led economic empowerment intervention on viral suppression among adolescents living with HIV . Using data from Suubi + Adherence , a longitudinal , cluster r and omized trial in southern Ug and a ( 2012–2017 ) , we examine the effect of the intervention on HIV RNA viral load , dichotomized between undetectable ( < 40 copies/ml ) and detectable ( ≥ 40 copies/ml ) . Cluster-adjusted comparisons of means and proportions were used to descriptively analyze changes in viral load between study arms while multi-level modelling was used to estimate treatment efficacy after adjusting for fixed and r and om effects . At 24-months post intervention initiation , the proportion of virally suppressed participants in the intervention cohort increased tenfold ( ΔT2−T0 = + 10.0 , p = 0.001 ) relative to the control group ( ΔT2−T0 = + 1.1 , p = 0.733 ) . In adjusted mixed models , simple main effects tests identified significantly lower odds of intervention adolescents having a detectable viral load at both 12- and 24-months . Interventions addressing economic insecurity have the potential to bolster health outcomes , such as HIV viral suppression , by improving ART adherence among vulnerable adolescents living in low-re source environments . Further research and policy dialogue on the intersections of financial security and HIV treatment are warranted The use of savings products to promote financial inclusion has increasingly become a policy priority across sub-Saharan Africa , yet little is known about how families respond to varying levels of savings incentives and whether the promotion of incentivized savings in low-re source setting s may encourage households to restrict expenditures on basic needs . Using data from a r and omized controlled trial in Ug and a , we examine : 1 ) whether low-income households enrolled in an economic-empowerment intervention consisting of matched savings , workshops , and mentorship reduced spending on basic needs and 2 ) how varied levels of matching contributions affected household savings and consumption behavior . We compared primary school-attending AIDS-affected children ( N = 1,383 ) r and omized to a control condition with two intervention arms with differing savings-match incentives : 1:1 ( Bridges ) and 1:2 ( Bridges PLUS ) . We found that : 1 ) 24 months post-intervention initiation , children in Bridges and Bridges PLUS were more likely to have accumulated savings than children in the control condition ; 2 ) higher match incentives ( Bridges PLUS ) led to higher deposit frequency but not higher savings in the bank ; 3 ) intervention participation did not result in material hardship ; and 4 ) in both intervention arms , participating families were more likely to start a family business and diversify their assets Innovative combination HIV-prevention and microfinance interventions are needed to address the high incidence of HIV and other STIs among women who use drugs . Project Nova is a cluster-r and omized , controlled trial for drug-using female sex workers in two cities in Kazakhstan . The intervention was adapted from prior interventions for women at high risk for HIV and tailored to meet the needs of female sex workers who use injection or noninjection drugs . We describe the development and implementation of the Nova intervention and detail its components : HIV-risk reduction , financial-literacy training , vocational training , and a matched-savings program . We discuss session-attendance rates , barriers to engagement , challenges that arose during the sessions , and the solutions implemented . Our findings show that it is feasible to implement a combination HIV-prevention and microfinance intervention with highly vulnerable women such as these , and to address implementation challenges successfully . ResumenExiste la necesidad de una intervención innovadora que combine intervenciones de prevención del VIH y microfinanzas para manejar la alta incidencia de VIH u otras enfermedades de transmisión sexual con mujeres que usan drogas . Nova es un Ensayo Clínico Controlado Aleatorio Grupal para mujeres trabajadoras sexuales que usan drogas en dos ciudades en Kazakstán . La intervención fue adaptada de otras intervenciones anteriores dirigidas a mujeres con alto riesgo de contraer VIH y diseñada para satisfacer las necesidades de las mujeres trabajadoras sexuales que se inyectan o consumen drogas . Este documento describe el desarrollo y la implementación de la intervención Nova . Describimos los componentes de la intervención Nova , los cuales incluyen reducción del riesgo de VIH , entrenamiento en conocimiento financiero , entrenamiento vocacional , y programa de ahorros igualados . También describimos las tasas de asistencia a las sesiones , barreras para la participación , desafíos durante la implementación de las sesiones , y las soluciones implementadas . Los result ados muestran que es posible implementar una combinación de intervención de reducción del riesgo de VIH y micro-finanzas con mujeres altamente vulnerables y resolver problemas para manejar exitosamente los desafíos de la implementación Some evidence points to the positive effects of asset accumulation programs on mental health of children living in low-re source context s. However , no evidence exists as to why and how such impact occurs . Our study aims to underst and whether child poverty , child work , and household wealth serve as pathways through which the economic strengthening intervention affects the mental health of AIDS-orphaned children . The study employed a cluster-r and omized experimental design with a family-based economic strengthening intervention conducted among 1410 school-going AIDS-orphaned children ages 10 and 16 years old in 48 primary schools in South Western Ug and a. To test the hypothesized relationships between the intervention , mediators ( household wealth , child poverty , and child 's work ) and mental health , we ran structural equation models that adjust for clustering of individuals within schools and account for potential correlation among the mediators . We found significant unmediated effect of the intervention on children 's mental health at 24 months ( B = -0.59 ; 95 % CI : 0.93 , -0.25 ; p < 0.001 ; β = -0.33 ) . Furthermore , the results suggest that participation in the intervention reduced child poverty at 12 months , which in turn improved latent mental health outcome at 24 months ( B = -0.14 ; 95 % CI : -0.29 , -0.01 ; p < 0.06 ; β = -0.08 ) . In addition , though not statistically significant at the 0.05 level , at 36 and 48 months , mental health of children in the treatment group improved by 0.13 and 0.16 st and ard deviation points correspondingly with no evidence of mediation . Our findings suggest that anti-poverty programs that aim solely to improve household income may be less advantageous to children 's mental health as compared to those that are specifically targeted towards reducing the impact of poverty on children . Further studies using more comprehensive measures of child work and age-appropriate child mental health may shed more light on underst and ing the link between asset accumulation interventions , child labor and children 's mental health Background It is estimated that almost 20 % of the world ’s adolescents have experienced or are experiencing a mental health problem . Several factors have been associated with the onset of adolescent mental health disorders , including poverty , child abuse and violence , particularly among adolescent girls . This paper examines the effect of participating in a family-based economic strengthening intervention on the mental health well-being of female adolescent orphans impacted by HIV/AIDS in rural Ug and a. Methods Data utilized in this study was from the Bridges to the Future Study ( 2011–2016 ) , an economic empowerment intervention aim ed at improving health outcomes of orphaned children . Adolescents were r and omly assigned to either the control condition receiving bolstered st and ard of care services for orphaned adolescents ; or one of two treatment conditions receiving bolstered st and ard of care as well as an economic empowerment intervention comprising of a child development account , a mentorship program and workshops on financial management and microenterprise development . Data was collected at baseline , 12- and 24-months post intervention initiation . Multilinear regression analyses were conducted to examine the impact of an economic empowerment intervention on mental health functioning of female participants over time . Mental health functioning was measured by : ( 1 ) the Child Depression Inventory ; ( 2 ) Beck Hopelessness Scale ; and ( 3 ) Tennessee Self Concept Scale . Results Analysis results show an improvement in mental health functioning over time among female participants receiving the intervention compared to their control counterparts . Specifically , compared to participants in the control condition , participants receiving the intervention reported a reduction in depressive symptoms from baseline to 12-months follow-up ( b = − 1.262 , 95 % CI − 2.476 , − 0.047 ) , and an additional 0.645-point reduction between baseline and 24-months follow-up ( b = − 1.907 , 95 % CI − 3.192 , − 0.622 ) . Participants receiving the intervention reported significant improvement in their reported self-concept from baseline to 24 months follow-up ( b = 3.503 ( 95 % CI 1.469 , 5.538 ) compared to participants in the control condition . Conclusions Empowerment of young girls , either in the form of peer mentorship and /or economic strengthening seems to significantly improve the overall mental health functioning of adolescent girls impacted by HIV and AIDS in low-income setting ABSTRACT Several studies in sub-Saharan Africa have linked social support to better ART ( antiretroviral therapy ) adherence among adults living with HIV . Less is known about the role of social support and family cohesion in ART adherence among children below 18 years . This paper focuses on HIV-infected adolescents as they transition through the vulnerable developmental stage of adolescence to examine the association between family cohesion and social support , and ART adherence in southern Ug and a. We utilized baseline data from Suubi+Adherence study , a five-year r and omized longitudinal clinical trial with the overall goal of examining the impact and cost associated with an innovative asset-based social intervention to increase adherence to HIV treatment for HIV-infected adolescents in Ug and a. This study employed self-reports to measure social support , family cohesion and ART adherence to treatment from 702 participants in 39 clinics situated in southern Ug and a. Regression results indicated that after adjusting for socio-demographic characteristics that family cohesion and social support from caregivers/family were associated with self-reported adherence to ART among HIV-infected adolescents . Social support from classmates , teachers , and friends were not associated with ART adherence . Study results suggest that strengthening family relationships and promoting social support within families caring for adolescents living with HIV can be crucial in addressing ART adherence challenges among adolescents in sub-Saharan Africa ABSTRACT This paper examines the effect of an asset-based intervention on academic performance and school transition among orphaned and vulnerable children in Ug and a. Participants were r and omly assigned to either the control arm or two treatment arms receiving an asset-based intervention . Participants in the treatment arms scored better grade s ; and had higher odds of transitioning to post- primary education relative to the control arm . Programmes which target financial insecurity may have a positive impact on the educational achievement and progression of orphaned children . There is a need to consider incorporating asset-based interventions within the development of educational policy , especially in low-income countries PURPOSE This article examines gender differences in attitudes toward sexual risk-taking behaviors of acquired immune deficiency syndrome (AIDS)-orphaned youth participating in a r and omized control trial testing an economic empowerment intervention in rural Ug and a. METHODS Adolescents ( average age 13.7 years ) who had lost one or both parents to AIDS from 15 comparable schools were r and omly assigned to either an experimental ( n=135 ) or a control condition ( n=142 ) . Adolescents in the experimental condition , in addition to usual care , also received support and incentives to save money toward secondary education . RESULTS Findings indicate that although adolescent boys and girls within the experimental condition saved comparable amounts , the intervention appears to have benefited girls , in regard to the attitudes toward sexual risk-taking behavior , in a different way and to a lesser extent than boys . CONCLUSIONS Future research should investigate the possibility that adolescent girls might be able to develop equally large improvements in protective attitudes toward sexual risk taking through additional components that address gendered social norms OBJECTIVES We tested whether a structural intervention combining savings-led microfinance and HIV prevention components would achieve enhanced reductions in sexual risk among women engaging in street-based sex work in Ulaanbaatar , Mongolia , compared with an HIV prevention intervention alone . METHODS Between November 2011 and August 2012 , we r and omized 107 eligible women who completed baseline assessment s to either a 4-session HIV sexual risk reduction intervention ( HIVSRR ) alone ( n=50 ) or a 34-session HIVSRR plus a savings-led microfinance intervention ( n=57 ) . At 3- and 6-month follow-up assessment s , participants reported unprotected acts of vaginal intercourse with paying partners and number of paying partners with whom they engaged in sexual intercourse in the previous 90 days . Using Poisson and zero-inflated Poisson model regressions , we examined the effects of assignment to treatment versus control condition on outcomes . RESULTS At 6-month follow-up , the HIVSRR plus microfinance participants reported significantly fewer paying sexual partners and were more likely to report zero unprotected vaginal sex acts with paying sexual partners . CONCLUSIONS Findings advance the HIV prevention repertoire for women , demonstrating that risk reduction may be achieved through a structural intervention that relies on asset building , including savings , and alternatives to income from sex work |
12,842 | 31,873,926 | Findings demonstrate that cognitive exertion has a negative effect on subsequent physical performance that is not due to chance and suggest that previous meta- analysis results may have underestimated the overall effect | An emerging body of the literature in the past two decades has generally shown that prior cognitive exertion is associated with a subsequent decline in physical performance .
Two parallel , but overlapping , bodies of literature ( i.e. , ego depletion , mental fatigue ) have examined this question .
However , research to date has not merged these separate lines of inquiry to assess the overall magnitude of this effect .
The present work reports the results of a comprehensive systematic review and meta- analysis examining carryover effects of cognitive exertion on physical performance . | PURPOSE To assess the effects of mental fatigue on physical and technical performance in small-sided soccer games . METHODS Twenty soccer players ( age 17.8 ± 1.0 y , height 179 ± 5 cm , body mass 72.4 ± 6.8 kg , playing experience 8.3 ± 1.4 y ) from an Australian National Premier League soccer club volunteered to participate in this r and omized crossover investigation . Participants played 15-min 5-vs-5 small-sided games ( SSGs ) without goal keepers on 2 occasions separated by 1 wk . Before the SSG , 1 team watched a 30-min emotionally neutral documentary ( control ) , while the other performed 30 min of a computer-based Stroop task ( mental fatigue ) . Subjective ratings of mental and physical fatigue were recorded before and after treatment and after the SSG . Motivation was assessed before treatment and SSG ; mental effort was assessed after treatment and SSG . Player activity profiles and heart rate ( HR ) were measured throughout the SSG , whereas ratings of perceived exertion ( RPEs ) were recorded before the SSG and immediately after each half . Video recordings of the SSG allowed for notational analysis of technical variables . RESULTS Subjective ratings of mental fatigue and effort were higher after the Stroop task , whereas motivation for the upcoming SSG was similar between conditions . HR during the SSG was possibly higher in the control condition , whereas RPE was likely higher in the mental-fatigue condition . Mental fatigue had an unclear effect on most physical-performance variables but impaired most technical-performance variables . CONCLUSIONS Mental fatigue impairs technical but not physical performance in small-sided soccer games Purpose Given the important role of the brain in regulating endurance performance , this comparative study sought to determine whether professional road cyclists have superior inhibitory control and resistance to mental fatigue compared to recreational road cyclists . Methods After preliminary testing and familiarization , eleven professional and nine recreational road cyclists visited the lab on two occasions to complete a modified incongruent colour-word Stroop task ( a cognitive task requiring inhibitory control ) for 30 min ( mental exertion condition ) , or an easy cognitive task for 10 min ( control condition ) in a r and omized , counterbalanced cross-over order . After each cognitive task , participants completed a 20-min time trial on a cycle ergometer . During the time trial , heart rate , blood lactate concentration , and rating of perceived exertion ( RPE ) were recorded . Results The professional cyclists completed more correct responses during the Stroop task than the recreational cyclists ( 705±68 vs 576±74 , p = 0.001 ) . During the time trial , the recreational cyclists produced a lower mean power output in the mental exertion condition compared to the control condition ( 216±33 vs 226±25 W , p = 0.014 ) . There was no difference between conditions for the professional cyclists ( 323±42 vs 326±35 W , p = 0.502 ) . Heart rate , blood lactate concentration , and RPE were not significantly different between the mental exertion and control conditions in both groups . Conclusion The professional cyclists exhibited superior performance during the Stroop task which is indicative of stronger inhibitory control than the recreational cyclists . The professional cyclists also displayed a greater resistance to the negative effects of mental fatigue as demonstrated by no significant differences in perception of effort and time trial performance between the mental exertion and control conditions . These findings suggest that inhibitory control and resistance to mental fatigue may contribute to successful road cycling performance . These psychobiological characteristics may be either genetic and /or developed through the training and lifestyle of professional road cyclists It has been shown that the mental fatigue induced by prolonged self-regulation increases perception of effort and reduces performance during subsequent endurance exercise . However , the physiological mechanisms underlying these negative effects of mental fatigue are unclear . The primary aim of this study was to test the hypothesis that mental fatigue exacerbates central fatigue induced by whole-body endurance exercise . Twelve subjects performed 30 min of either an incongruent Stroop task to induce a condition of mental fatigue or a congruent Stroop task ( control condition ) in a r and om and counterbalanced order . Both cognitive tasks ( CTs ) were followed by a whole-body endurance task ( ET ) consisting of 6 min of cycling exercise at 80 % of peak power output measured during a preliminary incremental test . Neuromuscular function of the knee extensors was assessed before and after CT , and after ET . Rating of perceived exertion ( RPE ) was measured during ET . Both CTs did not induce any decrease in maximal voluntary contraction ( MVC ) torque ( p = 0.194 ) . During ET , mentally fatigued subjects reported higher RPE ( mental fatigue 13.9 ± 3.0 , control 13.3 ± 3.2 , p = 0.044 ) . ET induced a similar decrease in MVC torque ( mental fatigue –17 ± 15 % , control –15 ± 11 % , p = 0.001 ) , maximal voluntary activation level ( mental fatigue –6 ± 9 % , control –6 ± 7 % , p = 0.013 ) and resting twitch ( mental fatigue –30 ± 14 % , control –32 ± 10 % , p < 0.001 ) in both conditions . These findings reject our hypothesis and confirm previous findings that mental fatigue does not reduce the capacity of the central nervous system to recruit the working muscles . The negative effect of mental fatigue on perception of effort does not reflect a greater development of either central or peripheral fatigue . Consequently , mentally fatigued subjects are still able to perform maximal exercise , but they are experiencing an altered performance during submaximal exercise due to higher-than-normal perception of effort This study examined the effects of a self-talk intervention on selective attention in a state of ego depletion . Participants were 62 undergraduate students with a mean age of 20.02 years ( SD = 1.17 ) . The experiment was conducted in four consecutive sessions . Following baseline assessment , participants were r and omly assigned into experimental and control groups . A two-session training was conducted for the two groups , with the experimental group using self-talk . In the final assessment , participants performed a selective attention test , including visual and auditory components , following a task inducing a state of ego depletion . The analysis showed that participants of the experimental group achieved a higher percentage of correct responses on the visual test and produced faster reaction times in both the visual and the auditory test compared with participants of the control group . The results of this study suggest that the use of self-talk can benefit selective attention for participants in states of ego depletion Background Exposure to smoking-related cues leads to increased urge to smoke in regular cigarette smokers and resisting these urges requires considerable self-control . Purpose Adopting a re source depletion model , two studies tested the hypothesis that resisting smoking urges depletes self-control re sources . Methods Adopting a within- participants r and omized cross-over design , participants ( study 1 , N = 19 ; study 2 , N = 32 ) were exposed to smoking-related ( study 1 : smoking images ; study 2 : cigarette cue-exposure task ) and neutral ( study 1 : neutral images ; study 2 : drinking-straw task ) cues with presentation order r and omized . After each cue set , participants completed self-control tasks ( study 1 : h and grip task ; study 2 : h and grip and Stroop tasks ) , performance on which constituted dependent measures of self-control . Results Self-control task performance was significantly impaired when exposed to smoking-related cues compared to neutral cues . No significant presentation-order effects , or interaction effects between stimulus and presentation order , were found . Conclusions Findings corroborate our hypothesis that resisting smoking urges depletes cigarette smokers ’ self-control re sources and suggests that self-control capacity is governed by a limited re source The limited re source or strength model of self-control posits that the use of self-regulatory re sources leads to depletion and poorer performance on subsequent self-control tasks . We conducted four studies ( two with community sample s , two with young adult sample s ) utilizing a frequently used depletion procedure ( crossing out letters protocol ) and the two most frequently used dependent measures of self-control ( h and grip perseverance and modified Stroop ) . In each study , participants completed a baseline self-control measure , a depletion or control task ( r and omized ) , and then the same measure of self-control a second time . There was no evidence for significant depletion effects in any of these four studies . The null results obtained in four attempts to replicate using strong method ological approaches may indicate that depletion has more limited effects than implied by prior publications . We encourage further efforts to replicate depletion ( particularly among community sample s ) with full disclosure of positive and negative results Prior investigations have shown measurable performance impairments on continuous physical performance tasks when preceded by a cognitively fatiguing task . However , the effect of cognitive fatigue on bodyweight resistance training exercise task performance is unknown . In the current investigation 18 amateur athletes completed a full body exercise task preceded by either a cognitive fatiguing or control intervention . In a r and omized repeated measure design , each participant completed the same exercise task preceded by a 52 min cognitively fatiguing intervention ( vigilance ) or control intervention ( video ) . Data collection sessions were separated by 1 week . Participants rated the fatigue intervention with a significantly higher workload compared to the control intervention ( p < 0.001 ) . Additionally , participants self-reported significantly greater energetic arousal for cognitively fatiguing task ( p = 0.02 ) . Cognitive fatigue did not significantly impact number of repetitions completed during the exercise task ( p = 0.77 ) ; however , when cognitively fatigued , participants had decreased percent time-on-task ( 57 % ) relative to the no fatigue condition ( 60 % ; p = 0.04 ) . RPE significantly changed over time ( p < 0.001 ) , but failed to show significant differences between the cognitive fatigue intervention and control intervention ( p > 0.05 ) . There was no statistical difference for heart rate or metabolic expenditure as a function of fatigue intervention during exercise . Cognitively fatigued athletes have decreased time-on-task in bodyweight resistance training exercise tasks 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 The purpose of the present study was to examine the effects of a self-regulatory strength depletion manipulation on performance of a physical endurance ( isometric h and grip ) task . In addition , the effect of depletion on EMG activity in the working forearm muscles during the endurance task was explored . Sedentary undergraduates ( N=49 ) were r and omly assigned to either a cognitive depletion condition ( modified Stroop task ) or a control ( color word ) group and completed two maximal isometric exercise endurance trials separated by the cognitive task . Participants in the depletion group showed significant ( p<.05 ) degradations in performance and exhibited higher EMG activation on the second endurance trial ( p<.05 ) compared to controls . Results are consistent with the limited strength model of self-regulation and are interpreted in light of the central fatigue hypothesis Mental fatigue is a psychobiological state caused by prolonged periods of dem and ing cognitive activity . Although the impact of mental fatigue on cognitive and skilled performance is well known , its effect on physical performance has not been thoroughly investigated . In this r and omized crossover study , 16 subjects cycled to exhaustion at 80 % of their peak power output after 90 min of a dem and ing cognitive task ( mental fatigue ) or 90 min of watching emotionally neutral documentaries ( control ) . After experimental treatment , a mood question naire revealed a state of mental fatigue ( P = 0.005 ) that significantly reduced time to exhaustion ( 640 + /- 316 s ) compared with the control condition ( 754 + /- 339 s ) ( P = 0.003 ) . This negative effect was not mediated by cardiorespiratory and musculoenergetic factors as physiological responses to intense exercise remained largely unaffected . Self-reported success and intrinsic motivation related to the physical task were also unaffected by prior cognitive activity . However , mentally fatigued subjects rated perception of effort during exercise to be significantly higher compared with the control condition ( P = 0.007 ) . As ratings of perceived exertion increased similarly over time in both conditions ( P < 0.001 ) , mentally fatigued subjects reached their maximal level of perceived exertion and disengaged from the physical task earlier than in the control condition . In conclusion , our study provides experimental evidence that mental fatigue limits exercise tolerance in humans through higher perception of effort rather than cardiorespiratory and musculoenergetic mechanisms . Future research in this area should investigate the common neurocognitive re sources shared by physical and mental activity Purpose Mental fatigue can negatively impact on submaximal endurance exercise and has been attributed to changes in perceived exertion rather than changes in physiological variables . The impact of mental fatigue on maximal anaerobic performance is , however , unclear . Therefore , the aim of the present study was to induce a state of mental fatigue to examine the effects on performance , physiological and perceptual variables from subsequent tests of power , strength and anaerobic capacity . Methods Twelve participants took part in the single-blind , r and omised , crossover design study . Mental fatigue was induced by 90 min of the computer-based Continuous Performance Task AX version . Control treatment consisted of 90 min of watching emotionally neutral documentaries . Participants consequently completed countermovement jump , isometric leg extension and a 3-min all-out cycling tests . Results Results of repeated measures analysis of variance and paired t tests revealed no difference in any performance or physiological variable . Rating of perceived exertion tended to be greater when mentally fatigued ( mental fatigue = 19 ± 1 vs control = 18 ± 1 , p = 0.096 , $ $ \eta^{2}_{\text{p}}$$ηp2 = .232 ) and intrinsic motivation reduced ( mental fatigue = 11 ± 4 vs control = 13 ± 6 , p = 0.063 , d = 0.597 ) in the mental fatigue condition . Conclusions Near identical responses in performance and physiological parameters between mental fatigue and control conditions suggest that peripheral mechanisms primarily regulate maximal anaerobic exercise . Whereas mental fatigue can negatively impact submaximal endurance exercise , it appears that explosive power , voluntary maximal strength and anaerobic work capacity are unaffected Self-regulation consumes a form of strength or energy . The authors investigated aftereffects of self-regulation depletion on muscle-endurance performance in older adults . Participants ( N = 61 , mean age = 71 ) were r and omized to a self-regulation-depletion or control group and completed 2 muscle-endurance performance tasks involving isometric h and grip squeezing that were separated by a cognitive-depletion task . The depletion group showed greater deterioration of muscle-endurance performance than controls , F(1 , 59 ) = 7.31 , p = .009 . Results are comparable to those of younger adults in a similar study and support Baumeister et al. 's limited-strength model . Self-regulation may contribute to central -nervous-system fatigue ; however , biological processes may allow aging muscle to offset depletion of self-regulatory re sources affecting muscle-endurance performance The purpose of this study was to examine whether mental fatigue influences the perceived effort required to complete fairly light and hard effort self-paced exercise challenges . 12 participants completed 2 trials in a r and omised cross-over design . Each participant was required to complete a time-matched pre-exercise task : 1 ) a continuous cognitive activity test ( EXP condition ; n=12 ) , or 2 ) a time-matched passive neutral observation task ( CON condition ; n=12 ) . Following the pre-exercise task , participants performed 2 consecutive bouts of self-paced cycling exercise again in r and omized order at fairly light ( RPE 11 ) and hard ( RPE 15 ) effort . Physiological , psychological and EEG indices were measured throughout both conditions . EXP participants reported significantly greater sensations of fatigue ( p<0.01 ) and demonstrated greater EEG beta-b and activation compared with CON ( p<0.01 ) prior to exercise . Power outputs from the exercise bouts were significantly reduced for EXP in both self-paced : RPE 11 ( 83±7 vs. 99±7 W ; p=0.005 ) and RPE 15 ( 132±9 vs. 143±8 W ; p=0.028 ) trials . This study demonstrates that individuals with higher self-reported sensations of fatigue and elevations of EEG beta activity in the prefrontal cortex of the brain prior to exercise produce less work during self-paced exercise trials than in a control condition , probably due to an altered perception of effort PURPOSE To investigate the effects of mental fatigue on soccer-specific physical and technical performance . METHODS This investigation consisted of two separate studies . Study 1 assessed the soccer-specific physical performance of 12 moderately trained soccer players using the Yo-Yo Intermittent Recovery Test , Level 1 ( Yo-Yo IR1 ) . Study 2 assessed the soccer-specific technical performance of 14 experienced soccer players using the Loughborough Soccer Passing and Shooting Tests ( LSPT , LSST ) . Each test was performed on two occasions and preceded , in a r and omized , counterbalanced order , by 30 min of the Stroop task ( mentally fatiguing treatment ) or 30 min of reading magazines ( control treatment ) . Subjective ratings of mental fatigue were measured before and after treatment , and mental effort and motivation were measured after treatment . Distance run , heart rate , and ratings of perceived exertion were recorded during the Yo-Yo IR1 . LSPT performance time was calculated as original time plus penalty time . LSST performance was assessed using shot speed , shot accuracy , and shot sequence time . RESULTS Subjective ratings of mental fatigue and effort were higher after the Stroop task in both studies ( P < 0.001 ) , whereas motivation was similar between conditions . This mental fatigue significantly reduced running distance in the Yo-Yo IR1 ( P < 0.001 ) . No difference in heart rate existed between conditions , whereas ratings of perceived exertion were significantly higher at iso-time in the mental fatigue condition ( P < 0.01 ) . LSPT original time and performance time were not different between conditions ; however , penalty time significantly increased in the mental fatigue condition ( P = 0.015 ) . Mental fatigue also impaired shot speed ( P = 0.024 ) and accuracy ( P < 0.01 ) , whereas shot sequence time was similar between conditions . CONCLUSIONS Mental fatigue impairs soccer-specific running , passing , and shooting performance Perceptual sensitivity to a visual target presented in a r and om continuous sequence of targets and nontargets decreased rapidly over time when stimuli were highly de grade d visually but not when moderately de grade d or unde grade d. Large declines in sensitivity , independent of changes in response criterion , were found after only 5 minutes of observation . These rapid decrements of sensitivity to de grade d targets seem to result from dem and s on the limited capacity of visual attention ABSTRACT This study aim ed to investigate the impact of mental fatigue on soccer-specific decision-making . Twelve well-trained male soccer players performed a soccer-specific decision-making task on two occasions , separated by at least 72 h. The decision-making task was preceded in a r and omised order by 30 min of the Stroop task ( mental fatigue ) or 30 min of reading from magazines ( control ) . Subjective ratings of mental fatigue were measured before and after treatment , and mental effort ( referring to treatment ) and motivation ( referring to the decision-making task ) were measured after treatment . Performance on the soccer-specific decision-making task was assessed using response accuracy and time . Visual search behaviour was also assessed throughout the decision-making task . Subjective ratings of mental fatigue and effort were almost certainly higher following the Stroop task compared to the magazines . Motivation for the upcoming decision-making task was possibly higher following the Stroop task . Decision-making accuracy was very likely lower and response time likely higher in the mental fatigue condition . Mental fatigue had unclear effects on most visual search behaviour variables . The results suggest that mental fatigue impairs accuracy and speed of soccer-specific decision-making . These impairments are not likely related to changes in visual search behaviour This study examined the impact of a period of mental fatigue on manual dexterity , anticipation timing and repeated high intensity exercise performance . Using a r and omised , repeated measures experimental design , eight physically trained adults ( mean age = 24.8 ± 4.1 years ) undertook a 40 minute vigilance task to elicit mental fatigue or a control condition followed by four repeated Wingate anaerobic performance tests . Pre , post fatigue/control and post each Wingate test , manual dexterity ( Seconds ) , coincidence anticipation ( absolute error ) were assessed . A series of two ( condition ) by six ( time ) ways repeated measures ANOVAs indicated a significant condition by time interactions for manual dexterity time ( p = 0.021 ) and absolute error ( p = 0.028 ) . Manual dexterity and coincidence anticipation were significantly poorer post mental fatigue compared with control . There were no significant differences in mean power between conditions or across trials ( all p > 0.05 ) PURPOSE The purpose of the study was to investigate the effects of mental fatigue on intermittent running performance . METHODS Ten male intermittent team sports players performed two identical self-paced , intermittent running protocol s. The two trials were separated by 7 d and preceded , in a r and omized-counterbalanced order , by 90 min of either emotionally neutral documentaries ( control ) or the AX-continuous performance test ( AX-CPT ; mental fatigue ) . Subjective ratings of fatigue and vigor were measured before and after these treatments , and motivation was recorded before the intermittent running protocol . Velocity , heart rate , oxygen consumption , blood glucose and lactate concentrations , and ratings of perceived exertion ( RPE ) were measured throughout the 45-min intermittent running protocol . Session RPE was recorded 30 min after the intermittent running protocol . RESULTS Subjective ratings of fatigue were higher after the AX-CPT ( P = 0.005 ) . This mental fatigue significantly reduced velocity at low intensities ( 1.28 ± 0.18 m·s vs 1.31 ± 0.17 m·s ; P = 0.037 ) , whereas high-intensity running and peak velocities were not significantly affected . Running velocity at all intensities significantly declined over time in both conditions ( P < 0.001 ) . Oxygen consumption was significantly lower in the mental fatigue condition ( P = 0.007 ) . Other physiological variables , vigor and motivation , were not significantly affected . Ratings of perceived exertion during the intermittent running protocol were not significantly different between conditions despite lower overall velocity in the mental fatigue condition . Session RPE was significantly higher in the mental fatigue condition ( P = 0.013 ) . CONCLUSION Mental fatigue impairs intermittent running performance . This negative effect of mental fatigue seems to be mediated by higher perception of effort PURPOSE The 2-bout exercise protocol has been developed to diagnose nonfunctional overreaching and the " overtraining syndrome . " It consists of 2 maximal exercise bouts separated by 4 hours . Mental fatigue negatively influences performance , but the effects of its occurrence during the 2-bout exercise protocol have never been investigated . The aim of this study was to examine whether mental fatigue ( induced during the rest period ) influences physical and cognitive performance during/after the second exercise bout of the 2-bout exercise protocol . METHODS Nine healthy , well-trained male cyclists participated in a single-blind , r and omized , placebo-controlled crossover study . The intervention consisted of either 1.5-hour rest ( control ) or performing a computer-based Stroop task to induce mental fatigue . Cognitive ( Eriksen Flanker task ) , physiological ( lactate , maximum heart rate , and maximum wattage ) , and subjective data ( mental fatigue-visual analog scale , Profile of Mood States , and rating of perceived exertion ) were gathered . RESULTS Ratings of fatigue , tension , and mental fatigue were affected in the mental fatigue condition ( P < .05 ) . Neither physiological nor cognitive differences were found between conditions . Ratings of mental fatigue were already affected after the first maximum exercise test ( P < .05 ) . CONCLUSIONS Neither physical nor cognitive performance was affected by mental fatigue , but subjective ratings did reveal significant differences . It is recommended to exclude mentally challenging tasks during the 2-bout exercise protocol rest period to ascertain unaffected subjective test results . This study should be repeated in athletes diagnosed with nonfunctional overreaching/overtraining syndrome |
12,843 | 31,993,949 | There are subtle neural adaptations following resistance-training involving both cortical and subcortical adaptations that act to increase motoneurone activation and likely contribute to the training-related increase in muscle strength | Resistance-training causes changes in the central nervous system ( CNS ) ; however , the sites of these adaptations remain unclear .
To determine sites of neural adaptation to resistance-training by conducting a systematic review and meta- analysis on the cortical and subcortical responses to resistance-training . | INTRODUCTION We used transcranial magnetic stimulation ( TMS ) to investigate 3 weeks of unilateral leg strength training on ipsilateral motor cortex ( iM1 ) excitability , and short-latency intracortical inhibition ( SICI ) . METHODS Right leg dominant participants ( n = 14 ) were r and omly divided into either a strength training ( ST ) or control group . The ST group completed 9 training sessions ( 4 sets of 6 to 8 repetitions of single right leg squats ) . RESULTS We observed a 41 % increase in right leg strength , and a 35 % increase in strength of the untrained left leg ( P < 0.01 ) . There was a significant increase in motor evoked potential ( MEP ) amplitude recruitment curve for the untrained left leg ( P < 0.01 ) . SICI of the iM1 decreased by 21 % for the untrained left leg ( P < 0.01 ) . CONCLUSIONS The findings provide evidence for corticomotor adaptation for unilateral leg strength training within the iM1 that is modulated by changes in interhemispheric inhibition Trapezius muscle Hoffman ( H ) reflexes were obtained to investigate the neural adaptations induced by a 5-wk strength training regimen , based solely on eccentric contractions of the shoulder muscles . Twenty-nine healthy subjects were r and omized into an eccentric training group ( n = 15 ) and a reference group ( n = 14 ) . The eccentric training program consisted of nine training sessions of eccentric exercise performed over a 5-wk period . H-reflex recruitment curves , the maximal M wave ( Mmax ) , maximal voluntary contraction ( MVC ) force , rate of force development ( RFD ) , and electromyographic ( EMG ) voluntary activity were recorded before and after training . H reflexes were recorded from the middle part of the trapezius muscle by electrical stimulation of the C3/4 cervical nerves ; Mmax was measured by electrical stimulation of the accessory nerve . Eccentric strength training result ed in significant increases in the maximal trapezius muscle H reflex ( Hmax ) ( 21.4 % [ 5.5 - 37.3 ] ; P = 0.01 ) , MVC force ( 26.4 % [ 15.0 - 37.7 ] ; P < 0.01 ) , and RFD ( 24.6 % [ 3.2 - 46.0 ] ; P = 0.025 ) , while no significant changes were observed in the reference group . Mmax remained unchanged in both groups . A significant positive correlation was found between the change in MVC force and the change in EMG voluntary activity in the training group ( r = 0.57 ; P = 0.03 ) . These results indicate that the net excitability of the trapezius muscle H-reflex pathway increased after 5 wk of eccentric training . This is the first study to investigate and document changes in the trapezius muscle H reflex following eccentric strength training Purpose To test whether long-term cortical adaptations occur bilaterally following chronic unilateral training with a simple motor task . Methods Participants ( n = 34 ) were r and omly allocated to a training or control groups . Only the former completed a 4-week maximal-intensity isometric training of the right first dorsal interosseus muscle through key pinching . Maximal strength was assessed bilaterally in four different movements progressively less similar to the training task : key , tip and tripod pinches , and h and grip . Transcranial magnetic stimulation was used to probe , in the left and right primary h and motor cortices , a number of st and ard tests of cortical excitability , including thresholds , intra-cortical inhibition and facilitation , transcallosal inhibition , and sensory-motor integration . Results Training increased strength in the trained h and , but only for the tasks specifically involving the trained muscle ( key + 8.5 % ; p < 0.0005 ; tip + 7.2 % ; p = 0.02 ) . However , the effect size was small and below the cutoff for meaningful change . H and grip and tripod pinch were instead unaffected . There was a similar improvement in strength in the untrained h and , i.e. , a cross-education effect ( key + 6.4 % ; p = 0.02 ; tip + 4.7 % ; p = 0.007 ) . Despite these changes in strength , no significant variation was observed in any of the neurophysiological parameters describing cortico-spinal and intra-cortical excitability , inter-hemispheric inhibition , and cortical sensory-motor integration . Conclusions A 4-week maximal-intensity unilateral training induced bilaterally spatial- and task-specific strength gains , which were not associated to direct or crossed cortical adaptations . The observed long-term stability of neurophysiological parameters might result from homeostatic plasticity phenomena , aim ed at restoring the physiological inter-hemispheric balance of neural activity levels perturbed by the exercise . Trial registration number Clinical Trials.gov identifier NCT02010398 This study employed longitudinal measures of evoked spinal reflex responses ( Hoffman reflex , V wave ) to investigate changes in the activation of muscle and to determine if there are " linked " neural adaptations in the motor pathway following isometric resistance training . Twenty healthy , sedentary males were r and omly assigned to either the trained ( n = 10 ) or control group ( n = 10 ) . The training protocol consisted of 12 sessions of isometric resistance training of the plantar flexor muscles over a 4-wk period . All subjects were tested prior to and after the 4-wk period . To estimate changes in spinal excitability , soleus Hoffman ( H ) reflex and M wave recruitment curves were produced at rest and during submaximal contractions . Recruitment curves were analyzed using the slope method ( Hslp/Mslp ) . Modulation of efferent neural drive was assessed through evoked V wave responses ( V/Mmax ) at 50 , 75 , and 100 % maximal voluntary contraction ( MVC ) . After 4 weeks , MVC torque increased 20.0 + /- 13.9 % ( mean + /- SD ) in the trained group . The increase in MVC was accompanied by significant increases in the rate of torque development ( 42.5 + /- 13.3 % ) , the soleus surface electromyogram ( 60.7 + /- 30.8 % ) , voluntary activation ( 2.8 + /- 0.1 % ) , and the rate of activation ( 48.7 + /- 24.3 % ) . Hslp/Mslp was not altered by training ; however , V/Mmax increased 57.3 + /- 34.2 % during MVC . These results suggest that increases in MVC observed in the first few days of isometric resistance training can be accounted for by an increase in the rate of activation at the onset of muscle contraction . Augmentation of muscle activation may be due to increased volitional drive from supraspinal centers The purpose of this study was to examine the effects of a 5-wk unilateral , isometric strength-training program on plasticity in the spinal Hoffmann ( H- ) reflex in both the trained and untrained legs . Sixteen participants , 22 - 42 yr old , were assigned to either a control ( n = 6 ) or an exercise group ( n = 10 ) . Both groups were tested for plantar flexion maximal voluntary isometric contractions ( MVIC ) and soleus H-reflex amplitude in both limbs , at the beginning and at the end of a 5-wk interval . Participants in the exercise group showed significantly increased MVIC in both legs after training ( P < 0.05 ) , whereas strength was unchanged in the control group for either leg . Subjects in the exercise group displayed increased ( P < 0.05 ) H-reflex amplitudes on the ascending limb of the recruitment curve ( at an equivalent M wave of 5 % of the maximal M wave , H(A ) ) only in the trained leg . Maximal H-reflex and M-wave remained unchanged with training . Increased amplitude of H(A ) in the trained limb concurrent with increased strength suggests that spinal mechanisms may underlie the changes in strength , possibly because of increased alpha-motoneuronal excitability or reduced presynaptic inhibition . Despite a similar increase in strength in the contralateral limb of the exercise group , H(A ) amplitude was unchanged . We conclude that the cross-education effect of strength training may be due to supraspinal to a greater extent than spinal mechanisms The purpose of this study was to investigate whether neural adaptations following functional multiple-joint leg press training can induce neural adaptations to the plantar flexor muscles in a single-joint contraction task . Subjects were r and omised to a maximal strength training ( MST ) ( n = 10 ) or a control group ( n = 9 ) . MST consisted of 24 sessions ( 8 weeks ) of 4 × 4 repetitions of horizontal leg press using maximal intended velocity in the concentric phase with the movement ending in a plantar flexion . Neural adaptations in the soleus and gastrocnemius medialis ( GM ) were assessed by surface electromyographic activity and V-waves during maximum voluntary isometric contraction ( MVIC ) , and also by H-reflexes in the soleus during rest and 20 % MVIC . One repetition maximum leg press increased by 44 ± 14 % ( mean ± SD ; P < 0.01 ) . Plantar flexion MVIC increased by 20 ± 14 % ( P < 0.01 ) , accompanied by 13 ± 19 % ( P < 0.05 ) increase in soleus , but not GM surface electromyography . Soleus V/MSUP increased by 53 ± 66 % and in GM by 59 ± 64 % ( P < 0.05 ) . Normalised soleus H-reflexes remained unchanged by training . No changes occurred in the control group . These results suggest that leg press MST can induce neural adaptations in a single-joint plantar flexion MVIC task Effects of 6 mo of heavy-resistance training combined with explosive exercises on neural activation of the agonist and antagonist leg extensors , muscle cross-sectional area ( CSA ) of the quadriceps femoris , as well as maximal and explosive strength were examined in 10 middle-aged men ( M40 ; 42 + /- 2 yr ) , 11 middle-aged women ( W40 ; 39 + /- 3 yr ) , 11 elderly men ( M70 ; 72 + /- 3 yr ) and 10 elderly women ( W70 ; 67 + /- 3 yr ) . Maximal and explosive strength remained unaltered during a 1-mo control period with no strength training . After the 6 mo of training , maximal isometric and dynamic leg-extension strength increased by 36 + /- 4 and 22 + /- 2 % ( P < 0 . 001 ) in M40 , by 36 + /- 3 and 21 + /- 3 % ( P < 0.001 ) in M70 , by 66 + /- 9 and 34 + /- 4 % ( P < 0.001 ) in W40 , and by 57 + /- 10 and 30 + /- 3 % ( P < 0.001 ) in W70 , respectively . All groups showed large increases ( P < 0.05 - 0.001 ) in the maximum integrated EMGs ( iEMGs ) of the agonist vastus lateralis and medialis . Significant ( P < 0.05 - 0.001 ) increases occurred in the maximal rate of isometric force production and in a squat jump that were accompanied with increased ( P < 0.05 - 0 . 01 ) iEMGs of the leg extensors . The iEMG of the antagonist biceps femoris muscle during the maximal isometric leg extension decreased in both M70 ( from 24 + /- 6 to 21 + /- 6 % ; P < 0.05 ) and in W70 ( from 31 + /- 9 to 24 + /- 4 % ; P < 0.05 ) to the same level as recorded for M40 and W40 . The CSA of the quadriceps femoris increased in M40 by 5 % ( P < 0.05 ) , in W40 by 9 % ( P < 0.01 ) , in W70 by 6 % ( P < 0.05 ) , and in M70 by 2 % ( not significant ) . Great training-induced gains in maximal and explosive strength in both middle-aged and elderly subjects were accompanied by large increases in the voluntary activation of the agonists , with significant reductions in the antagonist coactivation in the elderly subjects . Because the enlargements in the muscle CSAs in both middle-aged and elderly subjects were much smaller in magnitude , neural adaptations seem to play a greater role in explaining strength and power gains during the present strength-training protocol Voluntary activation of muscle is commonly quantified by comparison of the extra force added by motor nerve stimulation during a contraction [ superimposed twitch ( SIT ) ] with that produced at rest by the same stimulus ( resting twitch ) . An inability to achieve 100 % voluntary activation implies that failure to produce maximal force output from the muscle must have occurred at a site at or above the level of the motoneurons . We have used cortical stimulation to quantify voluntary activation . Here , incomplete activation implies a failure at or above the level of motor cortical output . With cortical stimulation , it is inappropriate to compare extra force evoked during a contraction with the twitch evoked in resting muscle because motor cortical and spinal cord excitability both increase with activity . However , an appropriate " resting twitch " can be estimated . We previously estimated its amplitude by extrapolation of the linear relation between SIT amplitude and voluntary torque calculated from 35 contractions of > 50 % maximum ( Todd G , Taylor JL , and G and evia SC . J Physiol 551 : 661 - 671 , 2003 ) . In this study , we improved the utility of this method to enable evaluation of voluntary activation when it may be changing over time , such as during the development of fatigue , or in patients who may be unable to perform large numbers of contractions . We have reduced the number of contractions required to only three . Estimation of the resting twitch from three contractions was reliable over time with low variability . Furthermore , its reliability and variability were similar to the resting twitch estimated from 30 contractions and to that evoked by conventional motor nerve stimulation The purpose of this study was to investigate age-related differences in short-term training adaptations in cortical excitability and inhibition . Thirty young ( 21.9 ± 3.1 years ) and 30 older ( 72.9 ± 4.6 years ) individuals participated in the study . Each participant was r and omly assigned to a control ( n = 30 ) or a resistance training ( n = 30 ) group , with equal numbers of young and older subjects in each group . Participants completed 2 days of testing , separated by 2 weeks during which time the training group participated in resistance training of the ankle dorsiflexor muscles three times per week . During each testing session , transcranial magnetic stimulation was used to generate motor evoked potentials ( MEPs ) and silent periods in the tibialis anterior . Hoffmann reflexes ( H-reflexes ) and compound muscle action potentials ( M-waves ) were also evoked via electrical stimulation of the peroneal nerve . At baseline , young subjects had higher maximum voluntary contraction ( MVC ) force ( p = 0.002 ) , larger M-wave amplitude ( p < 0.001 ) , and longer duration silent periods ( p = 0.01 ) than older individuals , with no differences in the maximal amplitude of the MEP ( p = 0.23 ) or H-reflex ( p = 0.57 ) . In the trained group , MVC increased in both young ( 17.4 % ) and older ( 19.8 % ) participants ( p < 0.001 ) , and the duration of the silent period decreased by ~15 and 12 ms , respectively ( p < 0.001 ) . Training did not significantly impact MEP ( p = 0.69 ) or H-reflex amplitudes ( p = 0.38 ) . There were no significant changes in any measures in the control group ( p ≥ 0.19 ) across the two testing sessions . These results indicate that a reduction in cortical inhibition may be an important neural adaptation in response to training in both young and older adults The aim of this study was to investigate if , and via what mechanisms , resistance training of the plantar flexor muscles affects voluntary activation during maximal voluntary eccentric and concentric muscle actions . Twenty healthy subjects were r and omized into a resistance training group ( n = 9 ) or a passive control group ( n = 11 ) . Training consisted of 15 sessions of unilateral mainly eccentric plantar flexor exercise over a 5-wk period . During pre- and posttraining testing , dynamic plantar flexor strength was measured and voluntary activation was calculated using the twitch interpolation technique . The soleus Hoffman reflex ( H-reflex ) was used to assess motoneurone excitability and presynaptic inhibition of Ia afferents , whereas the soleus V-wave was used to test for changes in both presynaptic inhibition of Ia afferents and supraspinal inputs to the motoneurone pool . H-reflexes , V-waves , supramaximal M-waves , and twitches were evoked as the foot was moved at 5 degrees /s through an angle of 90 degrees during passive ankle rotations ( passive H-reflexes and M-waves ) and during maximal voluntary concentric and eccentric plantar flexions [ maximal voluntary contraction ( MVC ) H-reflexes , M-waves , and V-waves ] . Training induced significant improvements in plantar flexor strength and voluntary activation during both concentric and eccentric maximal voluntary actions . Soleus passive and MVC H-to-M ratios remained unchanged after training , whereas the soleus V-to-M ratio was increased during both concentric and eccentric contractions after training . No changes were found in the control group for any of the parameters . The enhanced voluntary strength could be attributed partly to an increase in voluntary activation induced by eccentric training . Since the passive and MVC H-to-M ratios remained unchanged , the increase in activation is probably not due to decreased presynaptic inhibition . The increased V-to-M ratio for both action types indicates that increased voluntary drive from supraspinal centers and /or modulation in afferents other than Ia afferents may have contributed to such an increase in voluntary activation 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 The purpose of this study was to investigate the effects of 4-week ( 16 sessions ) unilateral , maximal isometric strength training on contralateral neural adaptations . Subjects were r and omised to a strength training group ( TG , n = 15 ) or to a control group ( CG , n = 11 ) . Both legs of both groups were tested for plantar flexion maximum voluntary isometric contractions ( MVCs ) , surface electromyogram ( EMG ) , H-reflexes and V-waves in the soleus ( SOL ) and gastrocnemius medialis ( GM ) superimposed during MVC and normalised by the M-wave ( EMG/MSUP , HSUP/MSUP , V/MSUP , respectively ) , before and after the training period . For the untrained leg , the TG increased compared to the CG for MVC torque ( 33 % , P < 0.01 ) , SOL EMG/MSUP ( 32 % , P < 0.05 ) and SOL V/MSUP ( 24 % , P < 0.05 ) . For the trained leg , the TG increased compared to the CG for MVC torque ( 40 % , P < 0.01 ) , EMG/MSUP ( SOL : 38 % , P < 0.05 ; GM : 60 % , P < 0.05 ) and SOL V/MSUP ( 72 % , P < 0.01 ) . HSUP/MSUP remained unchanged for both limbs . No changes occurred in the CG . These results reinforce the concept that enhanced neural drive to the contralateral agonist muscles contributes to cross-education of strength The purpose of this experiment was to determine whether training-induced increases in maximal voluntary contraction ( MVC ) can be completely accounted for by increases in muscle cross-sectional area . Fifteen female university students were r and omly divided into a control ( N = 7 ) and an experimental ( N = 8) group . The experimental group underwent 8 wk of isometric resistance training of the knee extensors of one leg ; the other leg was the untrained control . Training consisted of 30 MVC.d-1 x 3 d.wk-1 x 8 wk . Extensor cross-sectional area ( CSA ) , assessed by computerized tomographic ( CT ) scanning of a cross-sectional slice at mid-thigh , was used as a measure of muscle hypertrophy . After 8 wk of training , MVC increased by 28 % ( P < 0.05 ) , CSA increased by 14.6 % ( P < 0.05 ) , and the amplitude of the electromyogram at MVC ( EMGmax ) was unchanged in the trained leg of the experimental subjects . The same measures in the untrained legs of the experimental subjects and in both legs of the control subjects were not changed after training . Although there was an apparent discrepancy between the increase in MCV ( 28 % ) and CSA ( 14.6 % ) , the ratio between the two , the specific tension ( N.cm-2 ) , was not significantly different after training . As a result of these findings , we conclude that in these subjects there is no evidence of nonhypertrophic adaptations to resistance training of this type and magnitude , and that the increase in force-generating capacity of the muscle is due to the synthesis of additional contractile proteins We examined the neuromuscular adaptations following 3 and 6 weeks of 80 vs. 30 % one repetition maximum ( 1RM ) resistance training to failure in the leg extensors . Twenty-six men ( age = 23.1 ± 4.7 years ) were r and omly assigned to a high- ( 80 % 1RM ; n = 13 ) or low-load ( 30 % 1RM ; n = 13 ) resistance training group and completed leg extension resistance training to failure 3 times per week for 6 weeks . Testing was completed at baseline , 3 , and 6 weeks of training . During each testing session , ultrasound muscle thickness and echo intensity , 1RM strength , maximal voluntary isometric contraction ( MVIC ) strength , and contractile properties of the quadriceps femoris were measured . Percent voluntary activation ( VA ) and electromyographic ( EMG ) amplitude were measured during MVIC , and during r and omly ordered isometric step muscle actions at 10–100 % of baseline MVIC . There were similar increases in muscle thickness from Baseline to Week 3 and 6 in the 80 and 30 % 1RM groups . However , both 1RM and MVIC strength increased from Baseline to Week 3 and 6 to a greater degree in the 80 % than 30 % 1RM group . VA during MVIC was also greater in the 80 vs. 30 % 1RM group at Week 6 , and only training at 80 % 1RM elicited a significant increase in EMG amplitude during MVIC . The peak twitch torque to MVIC ratio was also significantly reduced in the 80 % , but not 30 % 1RM group , at Week 3 and 6 . Finally , VA and EMG amplitude were reduced during submaximal torque production as a result of training at 80 % 1RM , but not 30 % 1RM . Despite eliciting similar hypertrophy , 80 % 1RM improved muscle strength more than 30 % 1RM , and was accompanied by increases in VA and EMG amplitude during maximal force production . Furthermore , training at 80 % 1RM result ed in a decreased neural cost to produce the same relative submaximal torques after training , whereas training at 30 % 1RM did not . Therefore , our data suggest that high-load training results in greater neural adaptations that may explain the disparate increases in muscle strength despite similar hypertrophy following high- and low-load training programs Purpose Neural adaptations to strength training have long been recognized , but knowledge of mechanisms remains incomplete . Using novel techniques and a design which limited experimental bias , this study examined if 4 wk of strength training alters voluntary activation and corticospinal transmission . Methods Twenty-one subjects were r and omized into strength training ( n = 10 ; 7 females , 3 males ; 23.5 ± 7.5 yr ; mean ± SD ) and control groups ( n = 11 ; 2 females , 9 males ; 23.0 ± 4.2 yr ) . Strength training involved 12 sessions of high-force isometric contractions of the elbow flexors . Before and after training , voluntary activation of the elbow flexors was assessed via transcranial magnetic stimulation . Also , for the first time , magnetic stimulation of corticospinal axons was used to examine spinal-level adaptations to training . The evoked responses , termed cervicomedullary motor-evoked potentials ( CMEPs ) , were acquired in resting biceps brachii in three arm postures . Muscle adaptations were assessed via electrical stimulation of biceps . Results Compared with the control group , the strength training group exhibited greater increases in maximal strength ( 12.8 % ± 6.8 % vs 0.0 % ± 2.7 % ; P < 0.001 ) , biceps electromyographic activity ( 27.8 % ± 25.9 % vs −5.2 % ± 16.8 % ; P = 0.002 ) , and voluntary activation ( 4.7 % ± 3.9 % raw change vs −0.1 % ± 5.2 % ; P = 0.034 ) . Biceps CMEPs in all arm postures were unchanged after training . Biceps twitch characteristics were also unchanged . Conclusions Four weeks of isometric strength training of the elbow flexors increased muscle strength and voluntary activation , without a change in the muscle . The improvement in activation suggests that voluntary output from the cortex was better able to recruit motoneurons and /or increase their firing rates . The lack of change in CMEPs indicates that neither corticospinal transmission nor motoneuron excitability was affected by training The onset of whole muscle hypertrophy in response to overloading is poorly documented . The purpose of this study was to assess the early changes in muscle size and architecture during a 35-day high-intensity resistance training ( RT ) program . Seven young healthy volunteers performed bilateral leg extension three times per week on a gravity-independent flywheel ergometer . Cross-sectional area ( CSA ) in the central ( C ) and distal ( D ) regions of the quadriceps femoris ( QF ) , muscle architecture , maximal voluntary contraction ( MVC ) , and electromyographic ( EMG ) activity were measured before and after 10 , 20 , and 35 days of RT . By the end of the training period , MVC and EMG activity increased by 38.9 + /- 5.7 and 34.8 % + /- 4.7 % , respectively . Significant increase in QF CSA ( 3.5 and 5.2 % in the C and D regions , respectively ) was observed after 20 days of training , along with a 2.4 + /- 0.7 % increase in fascicle length from the 10th day of training . By the end of the 35-day training period , the total increase in QF CSA for regions C and D was 6.5 + /- 1.1 and 7.4 + /- 0.8 % , respectively , and fascicle length and pennation angle increased by 9.9 + /- 1.2 and 7.7 + /- 1.3 % , respectively . The results show for the first time that changes in muscle size are detectable after only 3 wk of RT and that remodeling of muscle architecture precedes gains in muscle CSA . Muscle hypertrophy seems to contribute to strength gains earlier than previously reported ; flywheel training seems particularly effective for inducing these early structural adaptations 1 . The adaptations of the ankle dorsiflexor muscles and the behaviour of single motor units in the tibialis anterior in response to 12 weeks of dynamic training were studied in five human subjects . In each training session ten series of ten fast dorsiflexions were performed 5 days a week , against a load of 30 - 40 % of the maximal muscle strength . 2 . Training led to an enhancement of maximal voluntary muscle contraction ( MVC ) and the speed of voluntary ballistic contraction . This last enhancement was mainly related to neural adaptations since the time course of the muscle twitch induced by electrical stimulation remained unaffected . 3 . The motor unit torque , recorded by the spike-triggered averaging method , increased without any change in its time to peak . The orderly motor unit recruitment ( size principle ) was preserved during slow ramp contraction after training but the units were activated earlier and had a greater maximal firing frequency during voluntary ballistic contractions . In addition , the high frequency firing rate observed at the onset of the contractions was maintained during the subsequent spikes after training . 4 . Dynamic training induced brief ( 2 - 5 ms ) motor unit interspike intervals , or ' doublets ' . These doublets appeared to be different from the closely spaced ( + /-10 ms ) discharges usually observed at the onset of the ballistic contractions . Motor units with different recruitment thresholds showed doublet discharges and the percentage of the sample of units firing doublets was increased by training from 5.2 to 32.7 % . The presence of these discharges was observed not only at the onset of the series of spikes but also later in the electromyographic ( EMG ) burst . 5 . It is likely that earlier motor unit activation , extra doublets and enhanced maximal firing rate contribute to the increase in the speed of voluntary muscle contraction after dynamic training Cross-education strength training has being shown to retain strength and muscle thickness in the immobilized contralateral limb . Corticospinal mechanisms have been proposed to underpin this phenomenon ; however , no transcranial magnetic stimulation ( TMS ) data has yet been presented . This study used TMS to measure corticospinal responses following 3 weeks of unilateral arm training on the contralateral , immobilize arm . Participants ( n = 28 ) were r and omly divided into either immobilized strength training ( Immob + train ) immobilized no training ( Immob ) or control . Participants in the immobilized groups had their nondominant arm rested in a sling , 15 h/day for 3 weeks . The Immob + train group completed unilateral arm curl strength training , while the Immob and control groups did not undertake training . All participants were tested for corticospinal excitability , strength , and muscle thickness of both arms . Immobilization result ed in a group x time significant reduction in strength , muscle thickness and corticospinal excitability for the untrained limb of the Immob group . Conversely , no significant change in strength , muscle thickness , or corticospinal excitability occurred in the untrained limb of the Immob + train group . These results provide the first evidence of corticospinal mechanisms , assessed by TMS , underpinning the use of unilateral strength training to retain strength and muscle thickness following immobilization of the contralateral limb Purpose The corticospinal responses to skill training may be different to strength training , depending on how the strength training is performed . It was hypothesised that the corticospinal responses would not be different following skill training and metronome-paced strength training ( MPST ) , but would differ when compared with self-paced strength training ( SPST ) . Methods Corticospinal excitability , short-interval intra-cortical inhibition ( SICI ) and strength and tracking error were measured at baseline and 2 and 4 weeks . Participants ( n = 44 ) were r and omly allocated to visuomotor tracking , MPST , SPST or a control group . Results MPST increased strength by 7 and 18 % , whilst SPST increased strength by 12 and 26 % following 2 and 4 weeks of strength training . There were no changes in strength following skill training . Skill training reduced tracking error by 47 and 58 % at 2 and 4 weeks . There were no changes in tracking error following SPST ; however , tracking error reduced by 24 % following 4 weeks of MPST . Corticospinal excitability increased by 40 % following MPST and by 29 % following skill training . There was no change in corticospinal excitability following 4 weeks of SPST . Importantly , the magnitude of change between skill training and MPST was not different . SICI decreased by 41 and 61 % following 2 and 4 weeks of MPST , whilst SICI decreased by 41 and 33 % following 2 and 4 weeks of skill training . Again , SPST had no effect on SICI at 2 and 4 weeks . There was no difference in the magnitude of SICI reduction between skill training and MPST . Conclusions This study adds new knowledge regarding the corticospinal responses to skill and MPST , showing they are similar but different when compared with SPST Six young ( mean = 23 years ) and 6 older ( mean = 76 years ) adults participated in isometric resistance training 5 days/week for 6 weeks . The task involved isometric fifth finger abduction . Maximal motor unit discharge rates ( MUDRs ) were obtained from the abductor digiti minimi of each h and at 0 , 2 , 14 , and 42 days of training using a quadrifilar needle electrode and automatic spike recognition software . In agreement with previous findings , maximal MUDR at baseline was significantly lower in older adults ( P < 0.001 ) , averaging 51.5 ( + /-17.13 ) HZ in young and 43.3 ( + /-14.88 ) HZ in older adults . In response to resistance training , maximal voluntary force increased 25 % in young and 33 % in older subjects ( P < 0.001 ) . Maximal MUDR increased significantly ( 11 % young , 23 % older ) on day 2 [ F(3,36 ) = 2.58 , P < 0.05 ] , but in older subjects returned to baseline levels thereafter . These adaptations in abductor digiti minimi MUDR suggest a two-part response to strengthening fifth finger abduction : early disinhibition followed by altered MU activation Practicing skilled tasks that involve the use of the h and and fingers has been shown to lead to adaptations within the central nervous system ( CNS ) underpinning improvements in the performance of the acquired task . However , neural adaptations following a period of strength training in the h and is not well understood . In order to determine the neural adaptations to strength training , we compared the effect of isometric strength training of the right first dorsal interosseous ( FDI ) muscle on the electromyographic ( EMG ) responses to transcranial magnetic stimulation ( TMS ) over left M1 . The specific aim of the study was to investigate the corticospinal responses , including latency , motor-evoked potential amplitude ( MEP ) , and silent period duration ( SP ) following 4 week of strength training of the FDI muscle . Sixteen healthy adults ( 13 male , three female ; 24.12±5.21 years ) , were r and omly assigned into a strength training ( n=8 ) or control group ( n=8 ) . Corticospinal measures of active motor threshold ( AMT ) , MEP amplitude , and SP duration were obtained using TMS during 5 % and 20 % of maximal voluntary contraction force ( MVC ) pre and post 4 week strength training . Following training , MVC force increased by 33.8 % ( p=.01 ) in the training group compared to a 13 % increase ( p=.2 ) in the untrained group . There were no significant differences in AMT , latency , or MEP amplitude between groups following training . However , in the trained group , there was a 16 ms reduction in SP duration at 5 % of MVC ( p=.01 ) and 25 ms reduction in SP duration at 20 % of MVC ( p=.03 ) . These results demonstrate a task dependent adaptation in corticospinal inhibition via a reduction in cortical SP duration that may in part underpin the strength increases observed following strength training PURPOSE The objective of this study was to assess the effect of anodal transcranial direct current stimulation ( a-tDCS ) on voluntary dynamic strength and cortical plasticity when applied during a 3-wk strength training program for the wrist extensors . METHODS Thirty right-h and ed participants were r and omly allocated to the tDCS , sham , or control group . The tDCS and sham group underwent 3 wk of heavy-load strength training of the right wrist extensors , with 20 min of a-tDCS ( 2 mA ) or sham tDCS applied during training ( double blinded ) . Outcome measures included voluntary dynamic wrist extension strength , muscle thickness , corticospinal excitability , short-interval intracortical inhibition ( SICI ) , and silent period duration . RESULTS Maximal voluntary strength increased in both the tDCS and sham groups ( 14.89 % and 11.17 % , respectively , both P < 0.001 ) . There was no difference in strength gain between the two groups ( P = 0.229 ) and no change in muscle thickness ( P = 0.15 ) . The tDCS group demonstrated an increase in motor-evoked potential amplitude at 15 % , 20 % , and 25 % above active motor threshold , which was accompanied by a decrease in SICI during 50 % maximal voluntary isometric contraction and 20 % maximal voluntary isometric contraction ( all P < 0.05 ) . Silent period decreased for both the tDCS and sham groups ( P < 0.001 ) . CONCLUSION The application of a-tDCS in combination with strength training of the wrist extensors in a healthy population did not provide additional benefit for voluntary dynamic strength gains when compared with st and ard strength training . However , strength training with a-tDCS appears to differentially modulate cortical plasticity via increases in corticospinal excitability and decreases in SICI , which did not occur following strength training alone |
12,844 | 26,029,906 | In conclusion , only in 2 experimental human pain models , i.e. , stress-induced analgesia and rTMS , administration of MOR-antagonist demonstrated a consistent effect , presumably mediated by an EOS-dependent mechanisms of analgesia and hyperalgesia | Opioid antagonists are pharmacological tools applied as an indirect measure to detect activation of the endogenous opioid system ( EOS ) in experimental pain models .
The objective of this systematic review was to examine the effect of mu-opioid-receptor ( MOR ) antagonists in placebo-controlled , double-blind studies using ' inhibitory ' or ' sensitizing ' , physiological test paradigms in healthy human subjects . | Summary Individual differences in endogenous opioid function predict morphine analgesic responses , and these endogenous opioid differences mediate the association between greater laboratory‐evoked pain sensitivity and greater analgesic responses to morphine . ABSTRACT Predictors of responsiveness to opioid analgesic medications are not well understood . This study tested whether individual differences in endogenous opioid ( EO ) function are associated with analgesic responsiveness to morphine . In r and omized , counterbalanced order over 3 sessions , 45 chronic low back pain participants and 31 healthy controls received an opioid antagonist ( 8 mg naloxone ) , morphine ( 0.08 mg/kg ) , or placebo . Participants then engaged in 2 laboratory‐evoked pain tasks ( ischemic and thermal ) . Outcomes included pain threshold , pain tolerance , and pain ratings . Indexes of EO function and morphine analgesic responsiveness were derived for each measure as the difference in pain responses between the placebo condition and naloxone or morphine condition , respectively . For all 7 pain measures across the 2 laboratory pain tasks , greater EO function was associated with significantly lower morphine analgesic responsiveness ( P < 0.001–P = 0.02 ) . Morphine reduced pain responses of low EO individuals to levels similar to those of high EO individuals receiving placebo . Higher placebo condition – evoked pain sensitivity was associated with significantly greater morphine analgesic responsiveness for 5 of 7 pain measures ( P < 0.001–P = 0.02 ) . These latter associations were significantly mediated by EO function for 4 of these 5 pain outcomes ( all P values < 0.05 ) . In the laboratory‐evoked pain context , opioid analgesic medications may supplement inadequate EO analgesia , with little incremental benefit in those with preexisting high EO function . Implication s for personalized medicine are discussed THE discovery of opiate-like peptides ( endorphins ) in brain , blood and cerebrospinal fluid1–4 raises questions as to the physiological role of these substances . Given the prominent analgesic effects of opiates , the regulation of pain perception is a c and i date for endorphin action . Endorphins microinjected into the periacqueductal grey matter of rats induce analgesia which is reversed by naloxone , a pure narcotic antagonist5 . If endorphins play an active part in the regulation of pain , then naloxone administered to man should alter pain appreciation . Naloxone has not been shown to have analgesic , respiratory , euphoric , pupillary or electroencephalogram ( EEG ) effects in man6 . Studies in rats7,8 and one early study in man9 have suggested slight hyperalgesic effects with naloxone . El-Sobky et al.10 failed to demonstrate naloxone effects on electric shock pain judgments in five subjects . In the experiments reported here , subjects were divided into pain sensitive and pain insensitive subgroups . The insensitive subjects found shocks significantly more painful after naloxone administration while the sensitive group experienced them as less painful . Evoked potentials showed similar significant group differences . These results suggest that individual differences in pain sensitivity may relate to differences in an endorphin system Purpose Opioid therapy is associated with the development of tolerance and paradoxically increased sensitivity to pain . It has been suggested that buprenorphine is associated with a higher antihyperalgesia/analgesia ratio than μ-opioid receptor agonists . The primary outcome of this study was therefore to investigate relative differences in antihyperalgesia and analgesia effects between morphine and buprenorphine in an inflammatory pain model in volunteers . The secondary outcome was to examine the relationship between pain sensitivity and opioid-induced effects on analgesia , antihyperalgesia , and descending pain modulation . Subjects and methods Twenty-eight healthy subjects were included . The study was a double-blind , r and omized , placebo-controlled , five-arm crossover study with a multimodal ( electrical , mechanical , and thermal stimuli ) testing technique . After baseline assessment s , intravenous infusions of morphine ( 10/20 mg ) , buprenorphine ( 0.3/0.6 mg ) , or placebo ( normal saline ) were administered over a 210-minute period , during which a cold pressor test , heat injury ( 47 ° C , 7 minutes , 12.5 cm2 ) , and the first postburn assessment were done . After completion of the drug infusions , two additional postburn assessment s were done . The subjects were monitored during each 8-hour session by an anesthesiologist . Results For nearly all tested variables , significant dose-dependent analgesic effects were demonstrated . The median antihyperalgesia/analgesia ratio ( secondary hyperalgesia/heat injury relative to placebo ) for low-dose morphine was 0.01 ( interquartile range : −6.2 ; 9.9 ) , 0.00 ( −2.4 ; 2.1 ) for high-dose morphine , 0.03 ( −1.8 ; 2.1 ) for low-dose buprenorphine , and 0.00 ( −3.2 ; 1.1 ) for high-dose buprenorphine ( P > 0.466 ) . There were no significant differences in opioid responses between high and low pain-sensitive subjects ( P > 0.286 ) . High-dose buprenorphine , compared to placebo , was associated with a significantly enhanced action of the descending inhibitory pain control system ( P = 0.004 ) . Conclusion The present study , using multimodal testing technique , could not demonstrate any significant differences between morphine and buprenorphine in the profiles of antihyperalgesia and analgesia . Only high-dose buprenorphine was associated with a significant effect on the descending inhibitory pain control system & NA ; We investigated the role of endogenous opioid systems in the analgesic effects induced by repetitive transcranial magnetic stimulation ( rTMS ) . We compared the analgesic effects of motor cortex ( M1 ) or dorsolateral prefrontal cortex ( DLPFC ) stimulation before and after naloxone or placebo treatment , in a r and omized , double‐blind crossover design , in healthy volunteers . Three groups of 12 volunteers were selected at r and om and given active stimulation ( frequency 10 Hz , at 80 % motor threshold intensity , 1500 pulses per session ) of the right M1 , active stimulation of the right DLPFC , or sham stimulation , during two experimental sessions 2 weeks apart . Cold pain thresholds and the intensity of pain induced by a series of fixed‐temperature cold stimuli ( 5 , 10 , and 15 ° C ) were used to evaluate the analgesic effects of rTMS . Measurements were made at the left thenar eminence , before and 1 hour after the intravenous injection of naloxone ( bolus of 0.1 mg/kg followed by a continuous infusion of 0.1 mg/kg/h until the end of rTMS ) or placebo ( saline ) . Naloxone injection significantly decreased the analgesic effects of M1 stimulation , but did not change the effects of rTMS of the DLPFC or sham rTMS . This study demonstrates , for the first time , the involvement of endogenous opioid systems in rTMS‐induced analgesia . The differential effects of naloxone on M1 and DLPFC stimulation suggest that the analgesic effects induced by the stimulation of these 2 cortical sites are mediated by different mechanisms . Endogenous opioids are shown to be involved in the analgesic effects of repetitive transcranial magnetic stimulation of the motor cortex The pathophysiological mechanisms underlying fibromyalgia are still unknown , although some evidence points to endogenous opioid dysfunction . We examined how endogenous opioid antagonism affects pain and mood for women with and without fibromyalgia . Ten women with fibromyalgia and ten age- and gender-matched , healthy controls each attended two laboratory sessions . Each participant received naltrexone ( 50 mg ) at one session , and placebo at the other session , in a r and omized and double-blind fashion . Participants were tested for changes in sensitivity to heat , cold , and mechanical pain . Additionally , we collected measures of mood and opioid withdrawal symptoms during the laboratory sessions and at home the night following each session . At baseline , the fibromyalgia group exhibited more somatic complaints , greater sensory sensitivity , more opioid withdrawal somatic symptoms , and lower mechanical and cold pain-tolerance than did the healthy control group . Neither group experienced changes in pain sensitivity due to naltrexone administration . Naltrexone did not differentially affect self-reported withdrawal symptoms , or mood , in the fibromyalgia and control groups . Consistent with prior research , there was no evidence found for abnormal endogenous opioid activity in women with fibromyalgia IF endorphins modulate pain , then naloxone should affect pain behaviour even in subjects who have not received exogenous opiates . However , some naloxone studies cl aim a lack of effect1,2 , others a hyperalgesic effect3–5 , and others both hyperalgesic and analgesic effects6,7 . Such discrepancies may arise from the different methods used to induce and assess pain8 , and from variation in dose . We know of only one previous human study which used multiple doses of naloxone6 ; this indicated a dose-dependent bi-directional effect . In the present study , a clinical pain paradigm was used to generate a dose – response curve for naloxone . We report that naloxone produces analgesia at low doses and hyperalgesia at high doses Introduction Development of secondary hyperalgesia following a cutaneous injury is a central ly mediated , robust phenomenon . The pathophysiological role of endogenous opioid signalling to the development of hyperalgesia is unclear . Recent animal studies , carried out after the resolution of inflammatory pain , have demonstrated reinstatement of tactile hypersensitivity following administration of μ-opioid-receptor-antagonists . In the present study in humans , we analyzed the effect of naloxone when given after the resolution of secondary hyperalgesia following a first-degree burn injury . Methods Twenty-two healthy volunteers were included in this placebo-controlled , r and omized , double-blind , cross-over study . Following baseline assessment of thermal and mechanical thresholds , a first-degree burn injury ( BI ; 47 ° C , 7 minutes , thermode area 12.5 cm2 ) was induced on the lower leg . Secondary hyperalgesia areas around the BI-area , and separately produced by brief thermal sensitization on the contralateral thigh ( BTS ; 45 ° C , 3 minutes , area 12.5 cm2 ) , were assessed using a polyamide monofilament at pre-BI and 1 , 2 , and 3 hours post-BI . At 72 hrs , BI and BTS secondary hyperalgesia areas were assessed prior to start of a 30 minutes intravenous infusion of naloxone ( total dose 21 microg/kg ) or placebo . Fifteen minutes after start of the infusion , BI and BTS secondary hyperalgesia areas were reassessed , along with mechanical and thermal thresholds . Results Secondary hyperalgesia areas were demonstrable in all volunteers 1–3 hrs post-BI , but were not demonstrable at 72 hrs post-burn in 73–86 % of the subjects . Neither magnitude of secondary hyperalgesia areas nor the mechanical and thermal thresholds were associated with naloxone-treated compared to placebo-treated subjects . Conclusion Naloxone ( 21 microg/kg ) did not reinstate secondary hyperalgesia when administered 72 hours after a first-degree burn injury and did not increase BTS-generated hyperalgesia . The negative results may be due to the low dose of naloxone or insufficient tissue injury to generate latent sensitization In fMRI there are two classes of inference : one aims to make a comment about the " typical " characteristics of a population , and the other about " average " characteristics . The first pertains to studies of normal subjects that try to identify some qualitative aspect of normal functional anatomy . The second class necessarily applies to clinical neuroscience studies that want to make an inference about quantitative differences of a regionally specific nature . The first class of inferences is adequately serviced by conjunction analyses and fixed-effects models with relatively small numbers of subjects . The second requires r and om-effect analyses and larger cohorts & NA ; We investigated the role of the glutamatergic and endogenous opioidergic systems in the paradoxical pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin with a “ thermal grill ” . Two parallel r and omized , double‐blind , cross‐over studies , including two groups of 12 healthy volunteers , were carried out to compare the effects of i.v . ketamine or naloxone to those of placebo , on the sensations produced by a thermode ( i.e. thermal grill ) composed of six bars applied on the palmar surface of the right h and . The temperature of alternate ( even‐ and odd‐numbered ) bars could be controlled independently by Peltier elements to produce various patterns of the grill . During each experimental session we measured the effects of ketamine , naloxone or placebo on the intensity of : ( i ) paradoxical pain ; ( ii ) “ normal ” thermal ( heat and cold ) pain ; and ( iii ) non‐painful thermal ( warm and cool ) sensations . Ketamine administration result ed in a significant reduction of paradoxical pain intensity but did not alter normal pain or non‐painful thermal sensations . By contrast , naloxone had no effect on paradoxical pain , normal pain or non‐painful thermal sensations . This study demonstrates for the first time that the “ thermal grill illusion of pain ” can be modulated pharmacologically . This paradoxical pain , which involves the glutamatergic systems , acting through the NMDA receptors , but not the tonic endogenous opioids systems , might share some mechanisms with pathological pain In 30 human subjects , experimental pain was produced by either ischemia or cold-water immersion . In a double-blind procedure , intravenous doses of up to 10 milligrams of naloxone hydrochloride in saline were indistinguishable from similarly administered saline alone . There were no effects on subjective pain ratings , finger plethysmograph recordings , or responses to mood-state question naires . These laboratory procedures do not activate any functionally significant pain-attenuating or mood-altering effect of endorphins & NA ; It has been hypothesized that , in the absence of acute or chronic pain , a tonically active system exists involving opioid peptides , which ensures a certain level of pain insensitivity . Although various studies have failed to support this concept , it has been reported that in conditions of both experimentally induced and clinical pain , high doses of the opioid antagonist naloxone induced a state of hyperalgesia and thus seemed to set off this hypothetical system . Lower doses were , however , without effect or even acted as analgesics . This study investigated the effect of 5 and 20 mg naloxone i.v . , compared to placebo , on the perception of pain in healthy humans . Pain was induced by two methods , using electrical and thermal stimulation of the skin , which have previously been shown to be sensitive to the effects of opioid as well as of non‐steroidal anti‐inflammatory analgesics . Each of 12 males and 12 females participated in 3 experimental sessions , in which the treatments were administered double‐blind according to a Latin square design . Threshold and tolerance to electrically induced pain and threshold to thermally induced pain were measured at 30 min intervals for 90 min before and 90 min after drug administration . Electrical stimuli were square wave constant current impulses of linearly increasing intensity ; thermal stimuli were of constant intensity and variable duration . Threshold and tolerance to electrically induced pain were not altered by either dose of naloxone , whereas the threshold to thermally induced pain was significantly higher after both 5 and 20 mg naloxone than after placebo , the effects of the two naloxone doses not differing from each other . Subjects who were relatively pain sensitive did not react differently to the pain stimuli after naloxone administration than did subjects who were relatively pain insensitive . These results , which are consistent with those of previous studies , cast further doubt on the validity of the concept that there is , in the absence of pain , a tonically active system involving endogenous opioids , which ensures a level of pain insensitivity Background : Opioid antagonists may change the responses in models of experimental hyperalgesia . This indicates a possible involvement of the endogenous opioid system in these models . The aim of the present study was to evaluate whether activation of the endogenous opioid system could be demonstrated in the human burn injury model of cutaneous hyperalgesia , using an intravenous challenge with the non‐selective opioid antagonist naloxone The aims of this study were to assess the effects of a mu-opioid antagonist , naloxone , on endogenous opioid systems and to evaluate the effect of naloxone on the CNS response to mild noxious heat . Doubled-blinded experiments were performed in a cross-over design in 10 healthy male volunteers . Functional magnetic resonance imaging ( fMRI ) data were collected before and during the infusion and also during thermal stimuli . Increased signal was observed in a number of cortical and subcortical brain regions for naloxone versus saline infusion . Cortical activation was induced in regions including cingulate , prefrontal cortex , and insula . Subcortical regions showing increased signal change included hippocampus and entorhinal cortex . A 46 degrees C stimulus delivered to the back of the h and induced an overall increase in activation in a number of regions in the naloxone group that were not seen in the saline group ( e.g. , insula , orbitofrontal cortex , thalamus , and hippocampus ) . These results show that naloxone , even in the absence of psychophysical effects , produces activation in several brain regions that are known to have high levels of mu-opioid receptors and may be involved in endogenous analgesia . Our study is an example of how fMRI can measure subtle changes in brain activation induced by pharmacological agents without cognitive effects The purpose of this experiment was to examine the effects of the endogenous opioid system on forearm muscle pain and muscle sympathetic nerve activity ( MSNA ) during dynamic fatiguing exercise . Twelve college-age men ( 24 + /- 4 yr ) performed grade d ( 1-min stages ; 30 contractions/min ) h and grip to fatigue 1 h after the ingestion of either 60 mg codeine , 50 mg naltrexone , or placebo . Pain ( 0 - 10 scale ) and exertion ( 0 - 10 and 6 - 20 scales ) intensities were measured during the last 15 s of each minute of exercise and every 15 s during recovery . MSNA was measured continuously from the peroneal nerve in the left leg . Pain threshold occurred earlier [ 1.8 + /- 1 , 2 . 2 + /- 1 , 2.2 + /- 1 J : codeine , naltrexone , and placebo , respectively ] and was associated with a lower rating of perceived exertion ( RPE ) ( 2.7 + /- 2 , 3.6 + /- 2 , 3.8 + /- 2 : codeine , naltrexone , and placebo , respectively ) in the codeine condition compared with either the naltrexone or placebo conditions . There were no main effects ( i.e. , drugs ) or interaction ( i.e. , drugs x time ) for either forearm muscle pain or RPE during exercise [ pain : F ( 2 , 22 ) = 0.69 , P = 0.51 ] . There was no effect of drug on MSNA , heart rate , or blood pressure during baseline , exercise , or recovery . Peak exercise MSNA responses were 21 + /- 1 , 21 + /- 2.0 , and 21 + /- 2.0 bursts/30 s for codeine , naltrexone , and placebo conditions , respectively . Peak mean arterial pressure responses were 135 + /- 4 , 131 + /- 3 , and 132 + /- 4 mmHg for codeine , naltrexone , and placebo conditions , respectively . It is concluded that neither 60 mg codeine nor 50 mg naltrexone has an effect on forearm muscle pain , exertion , or MSNA during high- intensity h and grip to fatigue & NA ; Previous human studies have shown that the analgesic effect of high‐frequency TENS could not be reversed by low doses of naloxone . The aim of the present study was to reinvestigate the possible contribution of opioid receptors to high‐frequency TENS analgesia by using low ( 0.02 mg/kg ) and high ( 0.14 mg/kg ) doses of naloxone . Naloxone ( high and low doses ) and saline were administered intravenously to young healthy adults using a triple‐blind r and omized cross‐over design . For each visit , TENS ( 100 Hz , 60 & mgr;s ) was applied for 25 min to the external surface of the left ankle . TENS intensity was adjusted to obtain strong but comfortable ( innocuous ) paresthesias . Experimental pain was evoked with a 1 cm2 thermode applied on the lateral aspect of the left heel . Subjective pain scores were obtained before , during and after TENS . Because preliminary analyses showed that the order of presentation affected the pattern of results , only the first visit of every participant could be analyzed without fear of contamination from possible carry‐over effects . These revealed that TENS maintained its analgesic properties following the injection of saline ( p < .001 ) and the injection of a low dose of naloxone ( p < .05 ) . However , when a high dose of naloxone was administered , TENS analgesia was completely blocked ( p = .20 ) . These results suggest that high‐frequency TENS involves opioid receptors . An insufficient amount of opioid antagonist likely prevented previous human studies from discovering the importance of opioid receptors in producing high‐frequency TENS analgesia In man , heterotopic painful thermal conditioning stimuli induce parallel decreases in the spinal nociceptive flexion ( RIII ) reflex and the concurrent sensation of pain elicited by electrical stimulation of the sural nerve at the ankle . Such phenomena may be related to the diffuse noxious inhibitory controls ( DNIC ) which were initially described in the rat and subsequently documented in humans . In nine subjects in the present study , a 2-min application of a moderately noxious temperature ( 46 degrees C ) to the contralateral h and strongly depressed the RIII reflex elicited in the biceps femoris muscle by electrical stimulation of the sural nerve at 1.2 times the reflex threshold . These depressive effects were maximal during the 2nd min of the conditioning period , showing an almost complete inhibition of the RIII reflex which gradually recovered its baseline value 6 - 9 min after the end of the conditioning period . Using a double-blind , cross-over design , it was found that these inhibitory effects were completely blocked 5 min after naloxone hydrochloride administration ( 0.4 mg i.v . ) whereas the administration of saline was totally ineffective . The lifting of the inhibitions was compatible with the short duration of the pharmacological effects of naloxone in that the inhibitions were observed again 50 min after the naloxone injection . During all the experimental sessions , heart and respiratory rates remained stable at their control levels . It is concluded that the loop subserving DNIC which ascends from-- and redescends to -- the spinal cord involves an opioidergic link in man as in experimental animals . Possible implication s for hypoalgesia based on the principles of counter-irritation or elicited by naloxone are discussed The effect of 8 mg IV naloxone on pain appreciation was studied with electric shocks administered to the left forearm of 20 normal volunteers . Pain sensitivity was assessed with a psychophysical task and with evoked potentials ( EP ) to the pain stimuli which were found sensitive to opiate agonists and antagonists in previous experiments . Naloxone-induced hyperalgesia before and after 20 min of intermittent shock was assessed in a 3-day placebo crossover experiment design ed to provide control comparisons of time effects . EP amplitude enhancement with naloxone was significantly greater following 20 min of shocks than preceding them , while pain judgments were not significantly affected . Thus , naloxone increases pain sensitivity , especially after prolonged pain stimulation . This finding is consistent with endorphin mediation of stress-induced analgesia and raises the question of whether this type of response decrement over time is related to the phenomena of habituation UNLABELLED Some recent studies suggested a role of the endogenous opioid system in modulating opioid-induced hyperalgesia ( OIH ) . In order to test this hypothesis , we conducted a prospect i ve r and omized , placebo-controlled , 2-way crossover study in healthy human volunteers . We utilized a well-established model of inducing OIH after a brief exposure to the μ-opioid agonist remifentanil using intradermal electrical stimulation . Patients were exposed to a r and omized 90-minute infusion of remifentanil or saline placebo during 2 separate occasions . Development of OIH was quantified using changes in the average radius of the area of secondary hyperalgesia generated by electrical pain stimulation . A 23.6 % ( 20.2 ) increase in area of secondary hyperalgesia over baseline was observed in the postinfusion period of the remifentanil session , demonstrating development of OIH ( P = .03 ) . In order to test endogenous opioid system modulation of OIH , patients were given a 1-time bolus of naloxone , which had no effect on the size of the hyperalgesic lesion in either the remifentinal or placebo session . These results suggested that the endogenous opioid system did not appear to modulate OIH . PERSPECTIVE Experimental evidence suggested that the endogenous opioid system did not significantly affect opioid-induced hyperalgesia . Consequently , this study suggested that alternative mechanisms such as pronociceptive stimulation and neuroplastic changes might be responsible for expression of OIH & NA ; The effects of intense exercise on pain perception , mood , and plasma endocrine levels in man were studied under naloxone and saline conditions . Twelve long‐distance runners ( mean weekly mileage = 41.5 ) were evaluated on thermal , ischemie , and cold presser pain tests and on mood visual analogue scales ( VAS ) . Blood was drawn for determination of plasma levels of & bgr;‐endorphin‐like immunoreactivity ( BEir ) , growth hormone ( GH ) , adrenocorticotrophic hormone ( ACTH ) , and prolactin ( PRL ) . These procedures were undertaken before and after a 6.3 mile run at 85 % of maximal aerobic capacity . Subjects participated on two occasions in a double‐blind procedure counterbalanced for drug order : on one day they received 2 i.v . injections of naloxone ( 0.8 mg in 2 ml vehicle each ) at 20 min intervals following the run ; on the other day , 2 equal volume injections of normal saline ( 2 ml ) . Sensory decision theory analysis of the responses to thermal stimulation showed that discriminability , P(A ) , was significantly reduced post‐run under the saline condition , a hypoalgesic effect ; response bias , B , was unaffected . Ischemie pain reports were significantly reduced post‐run on the saline day , also a hypoalgesic effect . Naloxone reversed the post‐run ischemie but not thermal hypoalgesic effects . Joy , euphoria , cooperation , and conscientiousness VAS ratings were elevated post‐run ; naloxone attenuated the elevation in joy and euphoria ratings only . Plasma levels of BEir , ACTH , GH , and PRL were significantly increased post‐run . The results show that long‐distance running produces hypoalgesia and mood elevation in man . The effects of naloxone implicate endogenous opioid neural systems as mechanisms of some but not all of the run‐induced alterations in mood and pain perception & NA ; Opioid receptors occur in locations of strategic importance within the central nervous system for modulation of pain . Is pain reduced by ongoing inhibition mediated by activation of these receptors ? Experiments to date in which the opioid‐receptor antagonist , naloxone , is administered during a painful event have yielded unclear results . Topically applied capsaicin can be used to induce tonic pain of moderate to severe intensity without tissue injury and is an ideal stimulus for study ing acute pain modulation . We therefore conducted a placebo‐controlled double‐blind crossover study to investigate the effects of naloxone on capsaicin‐induced pain ( five men , four women , aged 29±5 years ) . Capsaicin ( 10 % ) was applied topically and subjects rated pain every 2 min . The subjects were told that any drug given to them could increase , decrease , or not change their pain sensation . Pain plateaued after 20 min . At 26 min subjects received either naloxone or placebo in double‐blind fashion . At 56 min subjects received the alternative ( placebo or naloxone ) . In a second session the order of presentation was reversed . The naloxone induced a significant increase in pain compared both to baseline ( P<0.01 ) and placebo ( P<0.01 ) . The peak effect , reached at 12–20 min after naloxone delivery , was 59 % greater than placebo . This experiment suggests that acute pain is actively suppressed by endogenous opioid‐receptor activation & NA ; A decrease in pain sensitivity during acute depression has been observed in several studies , apparently related to the severity of symptomatology . However , the question remains whether this relationship can be found only in heterogeneous groups of depressive patients or also in a single diagnostic group , such as major depression . In the present study , pain thresholds were assessed in 20 patients with major depression ( DSM‐III‐R ) and in 20 healthy controls . Two threshold methods with a differing impact of reaction time on the results were used . Contact heat was applied as a natural source of pain . With both methods the pain thresholds were significantly increased in the depressive patients . No relationship was found to the various symptoms of depression assessed by psychopathometric scales . In contrast to the pain thresholds , the thresholds of skin sensitivity for nonnoxious stimuli ( warmth , cold , vibration ) were only slightly increased . In sub sample s ( N = 10 in each group ) , naloxone ( 5 mg i.v . ) and placebo were administered in a double‐blind design . No systematic changes in pain thresholds occurred under either treatment . Our findings suggest that the decrease in skin sensitivity in major depression is specific to pain and not due to an increased reaction time . Moreover , the decrease appears to be related neither to a naloxone‐sensitive mechanism nor to symptomatology Plasma levels of beta‐endorphin ( BE ) , an endogenous opioid analgesic , are often reported as they relate to acute and chronic pain outcomes . However , little is known about what resting plasma BE levels might reveal about functioning of the endogenous opioid antinociceptive system . This study directly examined associations between resting plasma BE and subsequent endogenous opioid analgesic responses to acute pain in 39 healthy controls and 37 individuals with chronic low back pain ( LBP ) . Resting baseline levels of plasma BE were assessed . Next , participants received opioid blockade ( 8 mg naloxone i.v . ) or placebo in a double‐blind , r and omized , crossover design . Participants then underwent two acute pain stimuli : finger pressure ( FP ) pain and ischaemic ( ISC ) forearm pain . Blockade effects ( naloxone minus placebo pain ratings ) were derived to index endogenous opioid analgesic function . In placebo condition analyses for both pain stimuli , higher resting BE levels were associated with subsequently greater reported pain intensity ( p 's < 0.05 ) , with this effect occurring primarily in healthy controls ( BE × Participant Type interactions , p 's < 0.05 ) . In blockade effect analyses across both pain tasks , higher resting plasma BE predicted less subsequent endogenous opioid analgesia ( smaller blockade effects ; p 's < 0.05 ) . For the ISC task , these links were significantly more prominent in LBP participants ( BE × Participant Type Interactions , p 's < 0.05 ) . Results suggest that elevated resting plasma BE may be a potential biomarker for reduced endogenous opioid analgesic capacity , particularly among individuals with chronic pain . Potential clinical implication s are discussed & NA ; The analgesia result ing from electrical stimulation in the periventricular grey matter at the level of the posterior commissure in the human patient has been reversed by naloxone . This finding raises the possibility that such stimulation is effective because morphine receptor cells may be activated Objectives : There is controversy about combining opioids with different receptor affinities . We assessed the analgesic and antihyperalgesic effects of the & mgr;-agonist fentanyl and the partial & mgr;-agonist/&kgr;-antagonist buprenorphine in a human pain model , when given alone or in combination . Methods : Fifteen healthy male volunteers ( 22 to 35 y ) were included in this r and omized , double-blind , placebo-controlled , cross-over study . Transcutaneous electrical stimulation induced spontaneous acute pain and stable areas of secondary hyperalgesia . Pain intensities , measured on a numeric rating scale from 0 to 10 , and the size of the hyperalgesic areas were assessed before , during , and after an intravenous infusion of 1.5 µg/kg fentanyl , 1.5 µg/kg buprenorphine , a combination of 0.75 µg/kg fentanyl and buprenorphine each , or saline 0.9 % . Maximum effects of the treatments were compared by repeated measurement analysis of variance , and pharmacodynamic interaction models were fitted to the data . Results : Starting from a baseline value of numeric rating scale=6 , the maximum reduction of pain intensity after correction for placebo effects was 43.9±22.2 % after fentanyl , 35.0±23.0 % after buprenorphine , and 39.4±20.8 % after the combination ( mean±SD , P=0.24 ) . The maximum reduction of the hyperalgesic area was 38.3±39.0 % for fentanyl , 34.4±32.7 % for buprenorphine , and 30.0±53.8 % for the combination ( mean±SD , P=0.82 ) . The time courses were best described by pharmacodynamic models assuming an additive interaction . Discussion : For the doses administered in this study , buprenorphine and fentanyl showed an additive interaction Previous studies suggest that the antinociceptive action of paracetamol ( acetaminophen , APAP ) might involve descending inhibitory pain pathways and the opioidergic system : this study explores this issue in humans with naloxone , the opioid antagonist . After ethical approval , 12 healthy male volunteers were included in this r and omized , controlled , double-blind , crossover , four-arm study . They were administered intravenous paracetamol ( APAP 1 g ) or saline ( placebo , pl ) followed at 100 min with IV naloxone ( Nal 8 mg ) or saline , every week for 4 weeks . The amplitude of cerebral potentials evoked by thermal/painful stimuli applied on the arm was recorded nine times over 150 min , witnessing of pain integration at central level . Amplitude changes as well as areas under the curve ( AUCs ) over 150 min were compared for the four treatments by repeated measures ANOVA ( significance 0.05 ) . Amplitude changes were significant for APAP/pl vs. pl/pl at t150 : -44 % ( 95%CI -58 to -30 ) vs. -27 % ( 95%CI -37 to -17 ; P < 0.05 ) but not vs. APAP/Nal . AUC ( 0 - 150 ) of APAP/pl is significantly different from pl/pl ( -3452%.min ( 95%CI -4705 to -2199 ) vs. -933 % min ( 95%CI -2273 to 407 ; P = 0.015 ) but not from APAP/Nal ( -1731 % min ( 95%CI -3676 to 214 ; P = 0.08 ) and other treatments . AUC ( 90 - 150 ) is not significantly different . This pilot study shows for the first time in human volunteers that naloxone does not inhibit paracetamol antinociception , suggesting no significant implication of the opioid system in paracetamol mechanism of action : this needs be confirmed on a larger number of subjects A 20-minute session of 10 Hz repetitive transcranial magnetic stimulation ( rTMS ) of Brodmann Area ( BA ) nine of the left dorsolateral prefrontal cortex ( DLPFC ) can produce analgesic effects on postoperative and laboratory-induced pain . This analgesia is blocked by pretreatment with naloxone , a μ-opioid antagonist . The purpose of this sham-controlled , double-blind , crossover study was to identify the neural circuitry that underlies the analgesic effects of left DLPFC rTMS , and to examine how the function of this circuit , including midbrain and medulla , changes during opioid blockade . Fourteen healthy volunteers were r and omized to receive intravenous saline or naloxone immediately before sham and real left DLPFC rTMS on the same experimental visit . One week later , each participant received the novel pretreatment but the same stimulation paradigm . Using short sessions of heat on capsaicin-sensitized skin , hot allodynia was assessed during 3 Tesla functional magnetic resonance imaging ( fMRI ) scanning at baseline , post-sham rTMS , and post-real rTMS . Data were analyzed using whole-brain voxel-based analysis , as well as time series extraction s from anatomically-defined regions of interest representing midbrain and medulla . Consistent with previous findings , real rTMS significantly reduced hot allodynia pain ratings . This analgesia was associated with elevated blood oxygenation-level dependent ( BOLD ) signal in BAs 9 and 10 , and diminished BOLD signal in the anterior cingulate , thalamus , midbrain , and medulla during pain . Naloxone pretreatment largely abolished rTMS-induced analgesia , as well as rTMS-induced attenuation of BOLD signal response to painful stimuli throughout pain processing regions , including midbrain and medulla . These preliminary results suggest that left DLPFC rTMS drives top-down opioidergic analgesia The effects of a repetitive stress induced by anticipation of pain were studied on the following somato-vegetative parameters : monosynaptic reflex ( H reflex ) , nociceptive flexion reflex ( RIII reflex ) , heart rate and respiratory frequency , in normal trained volunteers . A progressive increase in heart rate and in respiratory frequency , as well as a facilitation in H reflex parallel to an inhibition of RIII reflex ( threshold increased ) were observed in all subjects as a function of repetition of stress during 45 min . At this moment , a double-blind injection of a strong dose of naloxone ( 4 mg ) result ed in a rapid exacerbation in vegetative responses ( tachycardia , polypnea ) as well as in an increase in the facilitation of the H reflex , whereas the RIII reflex was dramatically facilitated ( threshold decreased ) . In contrast , no significant change in these parameters was observed during placebo ( saline ) injection compared to a control situation ( no injection ) . These data strongly suggest that endogenous opioids are involved in the phenomenon of stress-induced analgesia in man . Moreover , they show that the release of opiates in these conditions possibly modulates non-specific structures which are known to be activated during stress or emotion Previous studies have shown that muscle exercise and low frequency transcutaneous nerve stimulation ( TNS ) give rise to an analgesic effect in humans and animals . Endorphin has been proposed to mediate this analgesia . In this investigation , the effect of muscle exercise and low frequency TNS , on dental pain thresholds was studied and the possible involvement of endorphinergic mechanisms was investigated using naloxone as an antagonist . Dental pain thresholds were measured in 11 volunteers following leg or arm exercise and after low frequency TNS of the h and s or face . After exercise ( 20 min ) or stimulation ( 30 min ) either 0.8 mg naloxone ( 2 ml ) or saline ( 2 ml ) was injected i.v . in a double-blind fashion . Pain thresholds were measured repetitively before and after exercise or stimulation . Both leg and arm exercise increased pain threshold . Stimulation of the h and s also increased pain threshold , but less than arm exercise . A marked increase in pain threshold was seen after face stimulation . These changes in pain threshold were unaffected following injections of either naloxone or saline , except for an early and short-lasting reduction when naloxone was injected following arm exercise . The increases in pain threshold following muscle exercise and after low frequency TNS , showed similarities suggesting that a common mechanism might be involved . The pain threshold increase after arm exercise could only be partially mediated by endorphinergic mechanisms Two double blind cross-over studies were performed using a submaximal effort tourniquet test ( SETT ) in healthy volunteers to investigate the role of endogenous opioids in placebo analgesia . In the first study IV naloxone significantly inhibited analgesia , miosis and sedation produced by the opioid dipipanone 10 mg in 12 subjects . In the second naloxone , which did not produce hyperalgesia , failed to inhibit significant placebo analgesia in 12 subjects . The results do not support the involvement of endogenous opioids in ischemic limb pain or placebo analgesia under these conditions & NA ; The heat pain threshold was measured with phasic and tonic stimuli under basal conditions and after naloxone administration in 10 anorectic and 10 bulimic patients as well as in 11 healthy control subjects . Under both kinds of stimulation , the basal threshold values were elevated in the bulimic patients and in some of the anorectic patients . Naloxone did not differ from placebo in its effect on the pain thresholds ( phasic and tonic ) , suggesting that a nonopioid mechanism was responsible for the threshold elevation found in the eating disorder patients . The plasma cortisol concentration was similar in the three groups and not correlated with the basal pain thresholds in the patients . Other indicators of dieting such as beta‐hydroxybutric acid and triiodothyronine also showed no correlation with the basal pain thresholds . Significant height correlations can be interpreted as weak evidence that neuropathy is the cause of the increase in the pain threshold & NA ; Different mechanisms were proposed for opioid‐induced analgesia and antihyperalgesia , which might result in different pharmacodynamics . To address this issue , the time course of analgesic and antihyperalgesic effects of intravenous ( i.v . ) and sublingual ( s.l . ) buprenorphine was assessed in an experimental human pain model . Fifteen volunteers were enrolled in this r and omized , double‐blind , and placebo controlled cross‐over study . The magnitude of pain and the area of secondary hyperalgesia following transcutaneous stimulation were repetitively assessed before and up to 150 min after administration of ( 1 ) 0.15 mg buprenorphine i.v . and placebo pill s.l . , ( 2 ) 0.2 mg buprenorphine s.l . and saline 0.9 % i.v . or ( 3 ) saline 0.9 % i.v . and placebo pill s.l . as a control . The sessions were separated by 2 week wash‐out periods . For both applications of buprenorphine the antihyperalgesic effects were more pronounced as compared to the analgesic effects ( 66±9 vs. 26±5 % and 43±10 vs. 10±6 % , for i.v . and s.l . application , respectively ) . This contrasts the pattern for the intravenous administration of pure μ‐receptor agonists in the same model in which the antihyperalgesic effects are weaker . The apparent bioavailability of buprenorphine s.l . as compared to buprenorphine i.v . was 58 % with a 15.8 min later onset of antinociceptive effects . The half‐life of buprenorphine‐induced analgesic and antihyperalgesic effects were 171 and 288 min , respectively . In contrast to pure μ‐receptor agonists , buprenorphine exerts a lasting antihyperalgesic effect in our model . It will be of major clinical interest whether this difference will translate into improved treatment of pain states dominated by central sensitization The hypothesis that painful stimuli activate the endogenous opioid ( endorphin ) system in humans was tested by examining the effect of the opiate antagonist naloxone on experimentally induced ischemic pain and on subjective mood ratings . Intravenous injections of saline or naloxone hydrochloride ( 2 and 10 mg ) were administered under double-blind conditions to 12 subjects . Naloxone did not affect the pain ratings . However , a significant dose-related effect of naloxone on tension-anxiety was found , suggesting that the endorphins . like exogenously administered opiates , may have antianxiety properties Objective Sex differences in pain sensitivity and stress reactivity have been well documented . Little is known about the role of the endogenous opioid system in these differences . This study was conducted to compare adrenocortical , pain sensitivity , and blood pressure responses to opioid blockade using naltrexone in men and women . Methods Twenty-six participants completed 2 sessions during which placebo or 50 mg of naltrexone was administered , using a double-blind , counterbalanced design . Thermal pain threshold and heat tolerance were assessed . Participants also rated pain during a 90-second cold pressor test ( CPT ) and completed the McGill Pain Question naire ( MPQ ) after each pain challenge . Blood and saliva sample s and cardiovascular and mood measures were obtained throughout the sessions . Results Plasma cortisol , adrenocorticotropin , beta endorphin , prolactin , and salivary cortisol levels increased similarly in men and women after naltrexone administration compared with placebo . Women reported more pain during both pain procedures and had lower thermal pain tolerance . In response to naltrexone , women exhibited reduced blood pressure responses and reduced MPQ pain ratings after CPT . No effects of naltrexone on these measures were found in men . Conclusions Although men and women exhibited similar hormonal responses to opioid receptor blockade , women reported less pain and showed smaller blood pressure responses during CPT . Results suggest differential effects of the endogenous opioid system on pain perception and blood pressure in men and women BACKGROUND The ( NMDA ) receptor plays a significant role in wind-up and spinal hypersensitivity and is involved in the occurrence of secondary hyperalgesia . Ketamine is an NMDA-receptor antagonist and has proven effective in alleviating secondary hyperalgesia in humans . Although it is disputed , the actions of ketamine have been ascribed not only to NMDA receptor antagonism , but also to opioid receptor agonism . A study therefore was design ed in which the abolishment of a previously demonstrated effect of ketamine on secondary hyperalgesia was sought by pretreatment with naloxone . METHODS Twenty-five volunteers were subjected to three treatment regimens . A st and ardized first-degree burn injury was induced . On appearance of primary and secondary hyperalgesia , one of the following infusion schemes was applied in a r and omized , double-blind , cross-over fashion : ( 1 ) infusion of naloxone ( 0.8 mg/15 min followed by 0.4 mg/h ) , succeeded by infusion of ketamine ( 0.3 mg x kg(-1 ) x 15 min(-1 ) followed by 0.3 mg x kg(-1 ) x h(-1 ) ) ; ( 2 ) infusion of placebo , succeeded by infusion of ketamine ( 0.3 mg x kg(-1 ) x 15 min(-1 ) followed by 0.3 mg x kg(-1 ) x h(-1 ) ) ; and ( 3 ) infusion of placebo , succeeded by infusion of placebo . Heat-pain detection thresholds , magnitude of secondary hyperalgesia around the burn injury , and side effects were determined . RESULTS Ketamine reduced secondary hyperalgesia . Naloxone did not affect the action of ketamine . The magnitudes of side effects were equal if the subjects received ketamine , regardless of preceding infusion of naloxone . CONCLUSIONS In this experimental setting , opioid receptor blockade does not inhibit ketamine-induced reductions of secondary hyperalgesia Nalmefene , a pure opiate antagonist structurally similar to naloxone , possesses a longer duration of action than naloxone at the same dose . However , the relative potency of these two antagonists is not known . This study was , therefore , design ed to establish their potency ratio and duration of action at equipotent doses . Sixteen healthy , adult volunteers were allocated to one of four groups of four subjects each . A continuous fen-tanyl infusion was started to obtain a target plasma concentration of 1.5 ng/mL. The extent of respiratory depression was evaluated at 20 min ( first depression ) by recording end-tidal CO2 ( ETCO2 ) , respiratory rate ( RR ) , arterial oxygen saturation ( Spo2 ) , arterial blood gases , and ventilatory response to a hypercapnic challenge . Consecutive groups then received 1 , 2 , 4 , and 8 μg/kg of naloxone and nalmefene , in a double-blind , cross-over fashion , on separate occasions . Fentanyl infusion was continued and ETco2 , Spo2 , and RR were recorded every 5 min until the values obtained at the first depression were reestablished ( second depression ) . Multiple blood sample s for plasma levels of the test drug and fentanyl were taken . Ventilatory function was assessed at baseline , first depression , 5 min after test drug administration , and at second depression . The ventilatory variables were compared using analysis of variance ( ANOVA ) . There was a significant improvement in the slope and intercept of the Co2 response curve produced by the increasing doses ( P < 0.05 ) . There was no difference in recovery of these variables between the two drugs at the same dose , implying that the doses were equipotent . The mean plasma concentrations of nalmefene and naloxone at which ventilatory depression recurred were 0.3 ± 0.08 ng/mL and 0.28 ± 0.05 ng/mL , respectively ( P > 0.05 ) . The duration of action of nalmefene was longer than naloxone over the dose range studied ( P < 0.01 ) . The initial volume of distribution ( V1 ) for naloxone was 0.29 L/kg and its steady-state volume of distribution ( Vdss ) was 2.64 L/kg . These values were similar to those for nalmefene ( V1 = 0.26 L/kg , Vdss = 2.28 L/kg ) . The clearance of naloxone ( 0.049 L/min ) was more rapid than that of nalmefene ( 0.019 L/min ) and thus , the elimination half-life of naloxone ( 54.5 min ) was significantly shorter than that of nalmefene ( 108 min ) ( P < 0.05 ) . We conclude that nalmefene is equipotent to naloxone , both in terms of dose ( mg/mg ) and plasma concentration ; however , due to its slower clearance , its duration of effect is prolonged compared to that of naloxone . ( Anesth Analg 1994;78:536–41 & NA ; Quantitative sensory testing ( QST ) is an instrument to assess positive and negative sensory signs , helping to identify mechanisms underlying pathologic pain conditions . In this study , we evaluated the test – retest reliability ( TR‐R ) and the interobserver reliability ( IO‐R ) of QST in patients with sensory disturbances of different etiologies . In 4 centres , 60 patients ( 37 male and 23 female , 56.4 ± 1.9 years ) with lesions or diseases of the somatosensory system were included . QST comprised 13 parameters including detection and pain thresholds for thermal and mechanical stimuli . QST was performed in the clinical ly most affected test area and a less or unaffected control area in a morning and an afternoon session on 2 consecutive days by examiner pairs ( 4 QSTs/patient ) . For both , TR‐R and IO‐R , there were high correlations ( r = 0.80–0.93 ) at the affected test area , except for wind‐up ratio ( TR‐R : r = 0.67 ; IO‐R : r = 0.56 ) and paradoxical heat sensations ( TR‐R : r = 0.35 ; IO‐R : r = 0.44 ) . Mean IO‐R ( r = 0.83 , 31 % unexplained variance ) was slightly lower than TR‐R ( r = 0.86 , 26 % unexplained variance , P < .05 ) ; the difference in variance amounted to 5 % . There were no differences between study centres . In a subgroup with an unaffected control area ( n = 43 ) , reliabilities were significantly better in the test area ( TR‐R : r = 0.86 ; IO‐R : r = 0.83 ) than in the control area ( TR‐R : r = 0.79 ; IO‐R : r = 0.71 , each P < .01 ) , suggesting that disease‐related systematic variance enhances reliability of QST . We conclude that st and ardized QST performed by trained examiners is a valuable diagnostic instrument with good test – retest and interobserver reliability within 2 days . With st and ardized training , observer bias is much lower than r and om variance . Quantitative sensory testing performed by trained examiners is a valuable diagnostic instrument with good interobserver and test – retest reliability for use in patients with sensory disturbances of different etiologies to help identify mechanisms of neuropathic and non‐neuropathic pain Objective : Elevated trait anger ( TRANG ; heightened propensity to experience anger ) is associated with greater pain responsiveness , possibly via associations with deficient endogenous opioid analgesia . This study tested whether acute anger arousal moderates the impact of TRANG on endogenous opioid analgesia . Methods : Ninety-four chronic low back pain ( LBP ) participants and 85 healthy controls received opioid blockade ( 8 mg of naloxone ) or placebo in a r and omized , counterbalanced order in separate sessions . Participants were r and omly assigned to undergo either a 5-minute anger recall interview ( ARI ) or a neutral control interview across both drug conditions . Immediately after the assigned interview , participants engaged sequentially in finger pressure and ischemic forearm pain tasks . Opioid blockade effects were derived ( blockade minus placebo condition pain ratings ) to index opioid antinociceptive function . Results : Placebo condition TRANG by interview interactions ( p values < .05 ) indicated that TRANG was hyperalgesic only in the context of acute anger arousal ( ARI condition ; p values < .05 ) . Blockade effect analyses suggested that these hyperalgesic effects were related to deficient opioid analgesia . Significant TRANG by interview interactions ( p values < .05 ) for both pain tasks indicated that elevated TRANG was associated with smaller blockade effects ( less endogenous opioid analgesia ) only in the ARI condition ( p values < .05 ) . Results for ischemic task visual analog scale intensity blockade effects suggested that associations between TRANG and impaired opioid function were most evident in LBP participants when experiencing anger ( type by interview by TRANG interaction ; p < .05 ) . Conclusions : Results indicate that hyperalgesic effects of TRANG are most prominent when acute anger is aroused and suggest that endogenous opioid mechanisms contribute . TRANG = trait anger ; ARI = anger recall interview ; NCI = neutral control interview ; LBP = low back pain ; BDI = Beck Depression Inventory ; STAI = State-Trait Anxiety Inventory ; MPQ-S = McGill Pain Question naire-Sensory subscale ; MPQ-A = McGill Pain Question naire-Affective subscale ; BP = blood pressure ; FP = finger pressure ; ISC = ischemic & NA ; We have previously shown that fibromyalgia ( FMS ) patients have enhanced temporal summation ( windup ) and prolonged decay of heat‐induced second pain in comparison to control subjects , consistent with central sensitization . It has been hypothesized that sensory abnormalities of FMS patients are related to deficient pain modulatory mechanisms . Therefore , we conducted several analyses to further characterize enhanced windup in FMS patients and to determine whether it can be central ly modulated by placebo , naloxone , or fentanyl . Pre‐drug baseline ratings of FMS and normal control ( NC ) groups were compared with determine whether FMS had higher pain sensitivity in response to several types of thermal tests used to predominantly activate A‐delta heat , C heat , or cold nociceptors . Our results confirmed and extended our earlier study in showing that FMS patients had larger magnitudes of heat tap as well as cold tap‐induced windup when compared with age‐ and sex‐matched NC subjects . The groups differed less in their ratings of sensory tests that rely predominantly on A‐delta‐nociceptive afferent input . Heat and cold‐induced windup were attenuated by saline placebo injections and by fentanyl ( 0.75 and 1.5 & mgr;g/kg ) . However , naloxone injection had the same magnitudes of effect on first or second pain as that produced by placebo injection . Hypoalgesic effects of saline placebo and fentanyl on windup were at least as large in FMS as compared to NC subjects and therefore do not support the hypothesis that pain modulatory mechanisms are deficient in FMS . To the extent that temporal summation of second pain ( windup ) contributes to processes underlying hyperalgesia and persistent pain states , these results indirectly suggest that these processes can be central ly modulated in FMS patients by endogenous and exogenous analgesic manipulations R and omised controlled trials are the best way to compare the effectiveness of different interventions . Only r and omised trials allow valid inferences of cause and effect . Only r and omised trials have the potential directly to affect patient care — occasionally as single trials but more often as the body of evidence from several trials , whether or not combined formally by meta- analysis . It is thus entirely reasonable to require higher st and ards for papers reporting r and omised trials than those describing other types of study . Like all studies , r and omised trials are open to bias if done badly.1 It is thus essential that r and omised trials are done well and reported adequately . Readers should not have to infer what was probably done , they should be told explicitly . Proper methodology should be used and be seen to have been used . Yet review s of published trials have consistently found major deficiencies in reporting,2 3 4 making the task Pain sensitivity decreases with increasing resting blood pressure . This blood pressure-pain interaction may be mediated by endogenous opioids which have been shown to affect both blood pressure and nociception . To test this hypothesis , we measured mean arterial blood pressure ( MAP ) , central venous pressure ( CVP ) , heart rate ( HR ) , muscle sympathetic nerve activity ( MSNA ) , serum catecholamines , and individual pain rating scales during 2 min periods of noxious mechanostimulation ( skin fold pinching ) in nine young ( 26 + /- 2 year ) , male normotensive ( NT ) subjects and in 12 age and weight matched males with borderline hypertension ( BHT ) . Measurements were performed before and after the i.v . administration of naloxone ( 0.15 mg/kg ) and placebo in a r and omized double-blind cross-over trial . In the pre-naloxone trials , pain led to similar changes in MAP , CVP , MSNA and plasma catecholamines in the two groups except for a higher increase in HR in the BHT group as compared to the NT group ( 3 + /- 1 vs. 1 + /- 1 bpm ; P < 0.005 ) . Opioid blockade with naloxone increased MSNA responses to pain in the NT group ( from 5 + /- 1 to 9 + /- 1 bursts/min , and , from 100 + /- 23 to 204 + /- 36 units/min , respectively ; P < 0.05 ) but did not significantly affect the MSNA response to pain in the BHT group . Pain induced responses of MAP , CVP , and catecholamines were not altered by naloxone in either group . Overall , there was a highly significant inverse correlation between pain perception and resting blood pressure which was not significantly affected by naloxone . The BHT subjects exhibited a lower pain perception compared to the NT subjects ( P < 0.005 ) . Naloxone increased pain rating in the NT group ( from 194 + /- 9 to 218 + /- 13 ; P < 0.005 ) but not in the borderline hypertensive group ( 160 + /- 8 vs. 168 + /- 10 ; P = 0.36 ) . Except for a decreased HR response in the BHT group , placebo had no effect on the responses to pain . Our data do not indicate a major role of the endogenous opioid system for the blood pressure-pain interaction in man . Endogenous opioids affect pain perception and sympathetic nerve activity responses to pain in normotensive men but their activity seems to be attenuated in borderline hypertensive subjects . Therefore , the lower pain sensitivity in human essential hypertension is probably mediated by non-opioid mechanisms We previously developed a spatial summation model and demonstrated that spatial summation of pain involves the activation of both excitatory and inhibitory systems . The aim of this study was to determine whether the endogenous pain inhibitory systems recruited by the spatial summation model are opioid-mediated by verifying if they could be blocked by the opioid antagonist naloxone . Twenty healthy volunteers ( 10 men , 10 women ) participated in a r and omized , four-session , cross-over study . Each session consisted of pain perception ratings ( visual analog scale ) taken during the immersion of different surfaces of the arm in circulating noxious cold water ( 12 degrees C ) . The arm was arbitrarily divided into eight segments from fingertips to shoulder . Two sessions were increasing ( from fingertips to shoulder ) and two sessions were decreasing ( from shoulder to fingertips ) . All sessions consisted of eight consecutive 2-min immersions separated by 5-min resting periods . Intravenous injections of naloxone hydrochloride ( 0.14 mg/kg ) or saline ( NaCl , 0.9 % ) were administered under double-blind conditions . We found that during the control session ( saline injection ) there was a significant difference in pain intensity ratings between the increasing and decreasing sessions . The decreasing session result ed in lower pain intensity . As previously demonstrated , this lowering of the perception curve seems to be due to a large recruitment of inhibitory systems at the beginning of the decreasing session as opposed to a gradual recruitment during the increasing session . However , during the opioid inhibition session ( naloxone injection ) no differences were found between the increasing and decreasing sessions . Naloxone inhibited the endogenous pain inhibitory systems activated by the spatial summation model , suggesting that these systems have an opioid-mediated component , as previously reported for diffuse noxious inhibitory controls The analgesic effects of a repetitive stress induced by anticipation of pain ( noxious footshock ) were studied on both the threshold of a nociceptive flexion reflex and the corresponding pain sensation after a 4-day-treatment of diazepam vs placebo ( cross-over and double-blind study ) in normal volunteers . During diazepam , the stressor stimulus produced a weaker depression on both nociceptive reflex and pain sensation than that observed during placebo . Furthermore , the reversal effect by naloxone was much more marked during placebo than during diazepam . These data clearly suggest a possible moderating action of benzodiazepine brain type receptors upon the endogenous opiate systems involved in the phenomenon of stress-induced analgesia in humans & NA ; Elevated resting blood pressure is associated with decreased pain sensitivity in both animals and humans . Recent evidence suggests that this relationship may be mediated by endogenous opioid peptides in hypertensives , but the precise mechanism has not been investigated in normotensives . We examined the effect of opioid receptor blockade with naloxone on the relationship between resting blood pressure and pain sensitivity in normotensive humans . Sixteen young adults were given cold pressor and h and grip challenges after treatment with either naloxone or saline in a placebo‐controlled , within‐subject design . Multiple regression procedures indicated that resting systolic blood pressure was a significant predictor of cold pain ratings even after the effects of naloxone were statistically controlled . The interaction between systolic blood pressure and opioid blockade was non‐significant . These data suggest that the relationship between resting blood pressure and pain sensitivity in normotensive humans is mediated , at least in part , by non‐opioid mechanisms Twelve normal male volunteers received saline control , low-dose naloxone , and high-dose naloxone infusions during three weekly sessions . The sessions were 16 hr long : 1 hr for predrug assessment s , 8 hr during which either naloxone or saline was infused in a double-blind procedure , and a 7-hr postdrug observation period . The 8-hr infusions of naloxone had no effect on experimental ischemic arm pain . In addition , the ischemic arm pain procedure did not significantly increase either plasma levels of cortisol or immunoreactive beta-endorphin , suggesting that the procedure was not stressful . The high-dose naloxone infusion result ed in a slightly aversive mood state and prevented the normal circadian decrease in cortisol levels . Both doses of naloxone increased systolic blood pressure and prevented the normal diurnal increase in temperature . The 8-hr infusions of naloxone did not result in changes in pain , mood , or physiological indices beyond what was present within a few hours after starting the infusion Analgesic medications are often tested in clinical laboratory studies by observing their ability to reduce the pain produced by noxious stimuli presented to healthy skin . These medications may then be used clinical ly to reduce disease-related hyperalgesia . This article describes a clinical laboratory model useful for testing a medication 's ability to reduce hyperalgesia in humans . Results demonstrate that ultraviolet ( UV ) light induces hyperalgesia , commonly prescribed analgesic medications reduce UV-induced hyperalgesia , and this UV-induced hyperalgesia model can be used to assess the time course of a medication 's antihyperalgesia effects . Coupled with participant-rated measures of drug liking and mood , this model may prove useful for predicting the clinical efficacy and side-effect profile of novel analgesic medications in cost-efficient and statistically powerful laboratory studies & NA ; In contrast to an expected preventive analgesic effect , clinical observations suggest that intraoperatively applied opioids can induce postoperative hyperalgesia . We tested the development of post‐infusion hyperalgesia in a newly developed experimental model of electrically induced pain and secondary mechanical hyperalgesia . In a double‐blind , placebo controlled , cross‐over study , 13 subjects received either saline placebo , remifentanil ( 0.05 or 0.1 & mgr;g/kg/min ) or naloxone ( 0.01 mg/kg ) . Remifentanil dose‐dependently reduced pain and mechanical hyperalgesia during the infusion , but upon withdrawal , pain and hyperalgesia increased significantly above control level ( p<0.01 and p<0.05 , respectively ) . Naloxone infusion similarly result ed in increased pain ( anti‐analgesia ) ( p<0.001 ) and mechanical hyperalgesia ( p<0.01 ) . Increased pain ratings following withdrawal of remifentanil significantly correlated to anti‐analgesia evoked by the & mgr;‐opioid antagonist naloxone ( p<0.01 ) and was of similar magnitude , suggesting inhibition of endogenous opioids as an underlying mechanism . In contrast , hyperalgesia after remifentanil was more pronounced than hyperalgesia after naloxone administration and did not correlate to the observed anti‐analgesic effects , suggesting the involvement of additional receptors systems other than the endorphin system The heat/capsaicin sensitization model is a new human experimental pain model that synergistically combines non-invasive physical and chemical methods of nociceptor stimulation to produce stable and long-lasting hyperalgesia with a low potential for skin injury . In 10 healthy volunteers the forearm was stimulated with a 45 degrees C thermode for 5 min to produce an area of secondary hyperalgesia . Applying capsaicin cream for 30 min further exp and ed the area of secondary hyperalgesia . Periodically heating the treated skin with a previously non-painful temperature of 40 degrees C re-kindled the sensitization enough to maintain stable areas of secondary hyperalgesia for 4h . The evoked pain was moderate and well tolerated . The heat/capsaicin sensitization model should be well suited for study ing pain mechanisms and testing new analgesics TOC summary Naloxone pretreatment significantly reduces left dorsolateral prefrontal cortex rTMS‐induced analgesia . ABSTRACT The concurrent rise of undertreated pain and opiate abuse poses a unique challenge to physicians and research ers alike . A focal , noninvasive form of brain stimulation called repetitive transcranial magnetic stimulation ( rTMS ) has been shown to produce acute and chronic analgesic effects when applied to dorsolateral prefrontal cortex ( DLPFC ) , but the anatomical and pharmacological mechanisms by which prefrontal rTMS induces analgesia remain unclear . Data suggest that DLPFC mediates top – down analgesia via gain modulation of the supraspinal opioidergic circuit . This potential pathway might explain how prefrontal rTMS reduces pain . The purpose of this sham‐controlled , double‐blind , crossover study was to determine whether left DLPFC rTMS‐induced analgesia was sensitive to μ‐opioid blockade . Twenty‐four healthy volunteers were r and omized to receive real or sham TMS after either intravenous saline or naloxone pretreatment . Acute hot and cold pain via quantitative sensory testing and hot allodynia via block testing on capsaicin‐treated skin were assessed at baseline and at 0 , 20 , and 40 minutes after TMS treatment . When compared to sham , real rTMS reduced hot pain and hot allodynia . Naloxone pretreatment significantly reduced the analgesic effects of real rTMS . These results demonstrate that left DLPFC rTMS‐induced analgesia requires opioid activity and suggest that rTMS drives endogenous opioidergic pain relief in the human brain . Further studies with chronic dosing regimens of drugs that block or augment the actions of opiates are needed to determine whether TMS can augment opiates in chronic or postoperative pain management |
12,845 | 29,370,791 | Conclusions Our results demonstrate that practice facilitation with regular , tailored follow up is a powerful component of a successful organizational change strategy .
Academic detailing alone or combined with audit and feedback alone is ineffective without intensive follow up .
Provision of educational material s and use of audit and feedback are often integral components of multifaceted implementation strategies .
However , we did n’t find examples where those relatively limited strategies were effective as st and alone interventions . | Background External change agents can play an essential role in healthcare organizational change efforts .
Results Academic detailing ( AD ) is the most prevalently used organizational change strategy employed as part of multi-component implementation strategies . | Background The primary aim of this study was to evaluate the effectiveness of an intervention to increase the implementation of healthy eating and physical activity policies and practice s by centre-based childcare services . The study also sought to determine if the intervention was effective in improving child dietary intake and increasing child physical activity levels while attending childcare . Methods A parallel group , r and omised controlled trial was conducted in a sample of 128 childcare services . Intervention strategies included provision of implementation support staff , securing executive support , staff training , consensus processes , academic detailing visits , tools and re sources , performance monitoring and feedback and a communications strategy . The primary outcome of the trial was the proportion of services implementing all seven healthy eating and physical activity policies and practice s targeted by the intervention . Outcome data were collected via telephone surveys with nominated supervisors and room leaders at baseline and immediately post-intervention . Secondary trial outcomes included the differences between groups in the number of serves consumed by children for each food group within the Australian Guide to Healthy Eating and in the proportion of children engaged in sedentary , walking or very active physical activity assessed via observation in a r and om sub sample of 36 services at follow-up . Results There was no significant difference between groups for the primary trial outcome ( p = 0.44 ) . Relative to the control group , a significantly larger proportion of intervention group services reported having a written nutrition and physical activity policy ( p = 0.05 ) and providing adult-guided activities to develop fundamental movement skills ( p = 0.01 ) . There were no significant differences between groups at follow-up on measures of child dietary intake or physical activity . Conclusions The findings of the trial were equivocal . While there was no significant difference between groups for the primary trial outcome , the intervention did significantly increase the proportion of intervention group services implementing two of the seven healthy eating and physical activity policies and practice s. High levels of implementation of a number of policies and practice s at baseline , significant obesity prevention activity in the study region and higher than previously reported intra-class correlation of child behaviours may , in part , explain the trial findings .Trial registration Australian Clinical Trials Registry ( reference ACTRN12612000927820 ) Background : Greater than 65 percent of the United States ( US ) population is overweight , with 32 percent obese . It is a problem in both developed and developing nations . While guidelines exist , counseling by physicians about obesity and weight loss is inconsistent , and physician approaches to obesity management have limited success . This study attempted to increase involvement in translating proven research into practice to improve physician awareness and improve outcomes of overweight/obesity . Twenty-one physicians in a suburban , middle class population in the Midwestern United States participated . Methods : Physician obesity awareness , weight , height , BMI , blood pressure , lipids , and glycohemoglobin were measured from 641 patients at baseline and were compared to 631 at 12-month follow-up . All 21 physicians received academic detailing and were presented with their clinical outcomes . Ten physicians received an Enhanced Intervention . They were additionally asked to place a sticker in the chart of their overweight or obese patients . Results : Fifty-three percent of physicians were not comfortable discussing obesity with their patients at baseline , decreasing to 0 % at followup ( p=0.041 ) . Reference to obesity management by Intervention physicians increased from 2.4 % to 9.2 % ( p=0.001 ) while for Enhanced Intervention physicians documentation increased from 3.9 % to 15.6 % ( p=0.002 ) . Those patients in the Enhanced Intervention group lost an average of 6.19 lbs ( 3.3 % ) ( p=0.083 ) during the one year period versus 4.6 lbs ( 2.5 % ) ( p=0.20 ) in the Intervention group . The BMI dropped 1.2 in the Intervention group and 0.72 in the Enhanced Intervention group . The data from both groups was pooled at both baseline and follow-up . The average weight of patients decreased from 185.7 lbs to 180.3 lbs ( excluding outliers weighing > 311 lbs ) . This 5.4 pound loss was significant ( p=0.027 ) . The BMI decreased from 30.1 to 29.1 ( p=0.095 ) . Cardiovascular co-morbidities improved . Conclusion : Obesity and overweight have a very high prevalence in a primary care community based setting s. Clinicians are not comfortable diagnosing and managing obese and overweight patients . A combination of academic detailing and presentation of outcomes to physicians will improve their awareness and result in improved clinical outcomes including weight loss Background : In developing effective interventions to increase colorectal cancer ( CRC ) screening in at risk population s , a necessary first requirement is feasibility . This paper describes how the RESPECT approach to health education guided the conceptualization and implementation of physician-directed academic detailing ( AD ) to increase practice -wide CRC screening uptake . Methods : Physician-directed AD was one intervention component in a large educational r and omized controlled trial to increase CRC screening uptake . Study participants , primarily urban minority , were aged 50 or older , insured for CRC screening with no out-of-pocket expense and out of compliance with current screening recommendations . The trial was conducted in the New York City metropolitan area . Participants identified their primary care physician ; 564 individuals were recruited , representing 459 physician practice s. Two-thirds of the physician practice s were r and omized to receive AD . The RESPECT approach , modified for AD , comprises : 1 ) Rapport , 2 ) Educate , but do n’t overwhelm , 3 ) Start with physicians where they are , 4 ) Philosophical orientation based on a humanistic approach to education , 5 ) Engagement of the physician and his/her office staff , 6 ) Care and show empathy , and 7 ) Trust . Feasibility was assessed as rate of AD delivery . Results : The AD was delivered to 283 ( 92.5 % ) of the 306 practice s assigned to receive it ; 222/283 ( 78.4 % ) delivered to the doctor . Conclusion : The AD was feasible and acceptable to implement across a range of clinical setting s. The RESPECT approach offers a framework for tailoring educational efforts , allowing flexibility , as opposed to strict adherence to a highly structured script or a universal approach OBJECTIVES To evaluate the effectiveness of efforts to translate and disseminate evidence -based guidelines about atypical antipsychotic use to nursing homes ( NHs ) . DESIGN Three-arm , cluster r and omized trial . SETTING NHs . PARTICIPANTS NHs in the state of Connecticut . MEASUREMENTS Evidence -based guidelines for atypical antipsychotic prescribing were translated into a toolkit targeting NH stakeholders , and 42 NHs were recruited and r and omized to one of three toolkit dissemination strategies : mailed toolkit delivery ( minimal intensity ) ; mailed toolkit delivery with quarterly audit and feedback reports about facility-level antipsychotic prescribing ( moderate intensity ) ; and in-person toolkit delivery with academic detailing , on-site behavioral management training , and quarterly audit and feedback reports ( high intensity ) . Outcomes were evaluated using the Reach , Effectiveness , Adoption , Implementation , Maintenance ( RE- AIM ) framework . RESULTS Toolkit awareness of 30 % ( 7/23 ) of leadership of low-intensity NHs , 54 % ( 19/35 ) of moderate-intensity NHs , and 82 % ( 18/22 ) of high-intensity NHs reflected adoption and implementation of the intervention . Highest levels of use and knowledge among direct care staff were reported in high-intensity NHs . Antipsychotic prescribing levels declined during the study period , but there were no statistically significant differences between study arms or from secular trends . CONCLUSION RE- AIM indicators suggest some success in disseminating the toolkit and differences in reach , adoption , and implementation according to dissemination strategy but no measurable effect on antipsychotic prescribing trends . Further dissemination to external stakeholders such as psychiatry consultants and hospitals may be needed to influence antipsychotic prescribing for NH residents Academic detailing is rarely practised in developing countries . A r and omized control trial on healthcare service was conducted to evaluate the impact of academic detailing programme on the adherence of primary healthcare providers in Banke district , Nepal , to childhood diarrhoea treatment guidelines recommended by World Health Organization/United Nations Children 's Fund ( WHO/UNICEF ) . The participants ( N=209 ) were systematic ally divided into control and intervention groups . Four different academic detailing sessions on childhood diarrhoea management were given to participants in the intervention group . At baseline , 6 % of the participants in the control and 8.3 % in the intervention group were adhering to the treatment guidelines which significantly ( p<0.05 ) increased among participants in the intervention ( 65.1 % ) than in the control group ( 16.0 % ) at the first follow-up . At the second follow-up , 69.7 % of participants in the intervention group were adhering to the guidelines , which was significantly ( p<0.05 ) greater than those in the control group ( 19.0 % ) . Data also showed significant improvement in prescribing pattern of the participants in the intervention group compared to the control group . Therefore , academic detailing can be used for promoting adherence to treatment guidelines in developing countries , like Nepal AIMS Improvement collaboratives consisting of various components are used throughout health care to improve quality , but no study has identified which components work best . This study tested the effectiveness of different components in addiction treatment services , hypothesizing that a combination of all components would be most effective . DESIGN An unblinded cluster-r and omized trial assigned clinics to one of four groups : interest circle calls ( group teleconferences ) , clinic-level coaching , learning sessions ( large face-to-face meetings ) and a combination of all three . Interest circle calls functioned as a minimal intervention comparison group . SETTING Out-patient addiction treatment clinics in the United States . PARTICIPANTS Two hundred and one clinics in five states . MEASUREMENTS Clinic data managers su bmi tted data on three primary outcomes : waiting-time ( mean days between first contact and first treatment ) , retention ( percentage of patients retained from first to fourth treatment session ) and annual number of new patients . State and group costs were collected for a cost-effectiveness analysis . FINDINGS Waiting-time declined significantly for three groups : coaching ( an average of 4.6 days/clinic , P = 0.001 ) , learning sessions ( 3.5 days/clinic , P = 0.012 ) and the combination ( 4.7 days/clinic , P = 0.001 ) . The coaching and combination groups increased significantly the number of new patients ( 19.5 % , P = 0.028 ; 8.9 % , P = 0.029 ; respectively ) . Interest circle calls showed no significant effect on outcomes . None of the groups improved retention significantly . The estimated cost per clinic was $ 2878 for coaching versus $ 7930 for the combination . Coaching and the combination of collaborative components were about equally effective in achieving study aims , but coaching was substantially more cost-effective . CONCLUSIONS When trying to improve the effectiveness of addiction treatment services , clinic-level coaching appears to help improve waiting-time and number of new patients while other components of improvement collaboratives ( interest circles calls and learning sessions ) do not seem to add further value BACKGROUND Management of acute maxillary sinusitis ( AMS ) is not optimal ; antibiotics are often prescribed for viral sinusitis , which leads to many problems including those with antimicrobial resistance . Guidelines have been proposed as a means to change the professional practice s. OBJECTIVE Our aim was to study whether a nationwide guidelines implementation programme has an effect on the management of AMS in primary care . METHODS A multi-centre r and omized controlled trial was conducted in 30 health centres ( HCs ) covering a population of 819 777 people from 1998 to 2002 . The participating HCs were r and omized to implement guidelines either according to a problem-based learning ( PBL ) or an academic detailing ( AD ) method facilitated by local GPs . Data were gathered during 1 week in November in all study years and also from external control HCs in 2002 . The main outcome measure was compliance with the key points of AMS management in national Current Care guidelines . RESULTS Implementation of guidelines produced minor changes towards the recommended practice s in the management of AMS . Use of the first-line drug amoxicillin increased slightly ( from 39 % to 48 % in AD centres and from 33 % to 45 % in PBL centres , controls 40 % ) . Proportion of courses of antibiotics with recommended duration increased in MIKSTRA study centres ( from 34 % to 40 % in AD centres and from 32 % to 47 % in PBL centres , controls 43 % ) . CONCLUSIONS A nationwide guidelines implementation project produced modest changes in the management of AMS . There were no significant differences between AD and PBL education methods . Less than half the HCs were able to realize the project as intended , which decreases the internal validity of the study . The guidelines implementation might have benefited of more focussed targets and approaches that took into account the problems and practice s of each HC AIM To study the effects of a team-based model for continuous quality improvement ( CQI ) on primary care practice management . DESIGN OF STUDY R and omised controlled trial . SETTING Twenty-six intervention and 23 control primary care practice s in the Netherl and s. METHOD Practice s interested in taking part in the CQI project were , after assessment of their practice organisation , r and omly assigned to the intervention or control groups . During a total of five meetings , a facilitator helped the teams in the intervention group select suitable topics for quality improvement and follow a structured approach to achieve improvement objectives . Checklists completed by an outreach visitor , question naires for the GPs , staff and patients were used to assemble data on the number and quality of improvement activities undertaken and on practice management prior to the start of the intervention and 1 year later . RESULTS Pre-test and post-test data were compared for the 26 intervention and 23 control practice s. A significant intervention effect was found for the number of improvement objectives actually defined ( 93 versus 54 , P<0.001 ) and successfully completed ( 80 versus 69 % of the projects , P<0.001 ) . The intervention group also improved on more aspects of practice management , as measured by our practice visit method , than the control group but none of these differences proved statistically significant . CONCLUSION The intervention exerted a significant effect on the number and quality of improvement projects undertaken and self-defined objectives met . Failure of the effects of the intervention on the other dimensions of practice management to achieve significance may be due to the topics selected for some of the improvement projects being only partly covered by the assessment instrument Background Small trials with short term follow up suggest pharmacists ’ interventions targeted at healthcare professionals can improve prescribing . In comparison with clinical guidance , contemporary statin prescribing is sub-optimal and achievement of cholesterol targets falls short of accepted st and ards , for patients with atherosclerotic vascular disease who are at highest absolute risk and who st and to obtain greatest benefit . We hypothesised that a pharmacist-led complex intervention delivered to doctors and nurses in primary care , would improve statin prescribing and achievement of cholesterol targets for incident and prevalent patients with vascular disease , beyond one year . Methods We allocated general practice s to a 12-month Statin Outreach Support ( SOS ) intervention or usual care . SOS was delivered by one of 11 pharmacists who had received additional training . SOS comprised academic detailing and practical support to identify patients with vascular disease who were not prescribed a statin at optimal dose or did not have cholesterol at target , followed by individualised recommendations for changes to management . The primary outcome was the proportion of patients achieving cholesterol targets . Secondary outcomes were : the proportion of patients prescribed simvastatin 40 mg with target cholesterol achieved ; cholesterol levels ; prescribing of simvastatin 40 mg ; prescribing of any statin and the proportion of patients with cholesterol tested . Outcomes were assessed after an average of 1.7 years ( range 1.4–2.2 years ) , and practice level simvastatin 40 mg prescribing was assessed after 10 years . Findings We r and omised 31 practice s ( 72 General Practitioners ( GPs ) , 40 nurses ) . Prior to r and omisation a subset of eligible patients were identified to characterise practice s ; 40 % had cholesterol levels below the target threshold . Improvements in data collection procedures allowed identification of all eligible patients ( n = 7586 ) at follow up . Patients in practice s allocated to SOS were significantly more likely to have cholesterol at target ( 69.5 % vs 63.5 % ; OR 1.11 , CI 1.00–1.23 ; p = 0.043 ) as a result of improved simvastatin prescribing . Subgroup analysis showed the primary outcome was achieved by prevalent but not incident patients . Statistically significant improvements occurred in all secondary outcomes for prevalent patients and all but one secondary outcome ( the proportion of patients with cholesterol tested ) for incident patients . SOS practice s prescribed more simvastatin 40 mg than usual care practice s , up to 10 years later . Interpretation Through a combination of educational and organisational support , a general practice based pharmacist led collaborative intervention can improve statin prescribing and achievement of cholesterol targets in a high-risk primary care based population . Trial Registration International St and ard R and omised Controlled Trials Register IS RCT Background Practice facilitation ( PF ) is an implementation strategy now commonly used in primary care setting s for improvement initiatives . PF occurs when a trained external facilitator engages and supports the practice in its change efforts . The purpose of this group-r and omized trial is to assess PF as an intervention to improve the delivery of chronic illness care in primary care . Methods A r and omized trial of 40 small primary care practice s who were r and omized to an initial or a delayed intervention ( control ) group . Trained practice facilitators worked with each practice for one year to implement tailored changes to improve delivery of diabetes care within the Chronic Care Model framework . The Assessment of Chronic Illness Care ( ACIC ) survey was administered at baseline and at one-year intervals to clinicians and staff in both groups of practice s. Repeated- measures analyses of variance were used to assess the main effects ( mean differences between groups ) and the within-group change over time . Results There was significant improvement in ACIC scores ( p < 0.05 ) within initial intervention practice s , from 5.58 ( SD 1.89 ) to 6.33 ( SD 1.50 ) , compared to the delayed intervention ( control ) practice s where there was a small decline , from 5.56 ( SD 1.54 ) to 5.27 ( SD 1.62 ) . The increase in ACIC scores was sustained one year after withdrawal of the PF intervention in the initial intervention group , from 6.33 ( SD 1.50 ) to 6.60 ( SD 1.94 ) , and improved in the delayed intervention ( control ) practice s during their one year of PF intervention , from 5.27 ( SD 1.62 ) to 5.99 ( SD 1.75 ) . Conclusions Practice facilitation result ed in a significant and sustained improvement in delivery of care consistent with the CCM as reported by those involved in direct patient care in small primary care practice s. The impact of the observed change on clinical outcomes remains uncertain . Trial registration This protocol followed the CONSORT guidelines and is registered per ICMJE guidelines : Clinical Trial Registration Number : NCT00482768 Background : Colorectal cancer ( CRC ) screening is recommended for all adults 50 to 75 years old , yet only slightly more than one-half of eligible people are current with screening . Because CRC screening is usually initiated upon recommendations of primary care physicians , interventions in these setting s are needed to improve screening . Objectives : To assess the impact of a quality improvement intervention combining electronic medical record based audit and feedback , practice site visits for academic detailing and participatory planning , and “ best- practice ” dissemination on CRC screening in primary care practice . Research Design : Two-year group r and omized trial . Subjects : Physicians , midlevel providers , and clinical staff members in 32 primary care practice s in 19 States caring for 68,150 patients 50 years of age or older . Measures : Proportion of active patients up-to- date ( UTD ) with CRC screening ( colonoscopy within 10 years , sigmoidoscopy within 5 years , or at home fecal occult blood testing within 1 year ) and having screening recommended within past year among those not UTD . Results : Patients 50 to 75 years in intervention practice s exhibited significantly greater improvement ( from 60.7 % to 71.2 % ) in being UTD with CRC screening than patients in control practice s ( from 57.7 % to 62.8 % ) , the adjusted difference being 4.9 % ( 95 % confidence interval , 3.8%–6.1 % ) . Recommendations for screening also increased more in intervention practice s with the adjusted difference being 7.9 % ( 95 % confidence interval , 6.3%–9.5 % ) . There was wide inter practice variation in CRC screening throughout the intervention . Conclusions : A multicomponent quality improvement intervention in practice s that use electronic medical record can improve CRC screening 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 STUDY OBJECTIVE To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control . DESIGN Cluster-r and omized trial . SETTING Academic health system using an ambulatory electronic medical record . SUBJECTS A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers . INTERVENTION Academic detailing , provision of provider-specific data about hypertension control , provision of educational material s to the provider , and provision of educational and motivational material s to patients . MEASUREMENTS AND MAIN RESULTS The primary outcome was blood pressure control , defined as a blood pressure measurement below 140/90 mm Hg , and was ascertained from electronic medical records over 6 months of follow-up . We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure . When we accounted for clustering by provider , this adjusted odds ratio was 1.13 ( 95 % confidence interval 0.87 - 1.47 ) . Adjusted odds ratios were 1.03 ( 95 % confidence interval 0.78 - 1.36 ) in patients whose blood pressure was controlled at baseline and 1.25 ( 95 % confidence interval 0.94 - 1.65 ) in those whose blood pressure was not . These odds ratios were not significantly different ( p=0.11 ) . CONCLUSIONS These results were consistent with no effect or , at best , a relatively modest effect of the intervention among patients with hypertension . Had we not included a concurrent control group , the data would have provided an unduly optimistic view of the effectiveness of the program . The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline Objective To assess the effect of educational outreach visits on antibiotic prescribing for acute dental pain in primary care . Study design R and omised controlled trial ( RCT ) . Setting General dental practice s in four health authority areas in Wales . Subjects and methods General dental practitioners were recruited to the study and r and omly allocated to one of the three study groups ( control group , guideline group or intervention group ) . Following the intervention , practitioners completed a st and ardised question naire for each patient that presented with acute dental pain . Interventions The control group received no intervention . The guideline group received educational material by post . The intervention group received educational material by post and an academic detailing visit by a trained pharmacist . The educational material included evidence -based guidelines on prescribing for acute dental pain and patient information leaflets . Main outcome measures The number of antibiotic prescriptions issued to patients presenting with dental pain and the number of ' inappropriate ' antibiotic prescriptions . Antibiotics were considered to be inappropriate if the patient did not have symptoms indicative of spreading infection . Results A total of 1,497 completed question naires were received from 23 , 20 and 27 general dental practitioners in the control , guideline and intervention group respectively . Patients in the intervention group received significantly fewer antibiotic prescriptions than patients in the control group ( OR ( 95 % CI ) 0.63 ( 0.41 , 0.95 ) ) and significantly fewer inappropriate antibiotic prescriptions ( OR ( 95 % CI ) 0.33 ( 0.21 , 0.54 ) ) . However , antibiotic and inappropriate antibiotic prescribing were not significantly different in the guideline group compared to the control group ( OR ( 95 % CI ) 0.83 ( 0.55 , 1.21 ) and OR ( 95 % CI ) 0.82 ( 0.53 , 1.29 ) respectively ) . Conclusions Strategies based upon educational outreach visits may be successfully employed to rationalise antibiotic prescribing by dental practitioners Background The growing population living with chronic conditions calls for efficient healthcare-planning and effective care . Implementing disease-management-programmes is one option for responding to this dem and . Knowledge is scarce about the effect of implementation processes and their effect on patients ; only few studies have reported the effectiveness of disease-management-programmes targeting patients with chronic obstructive pulmonary disease ( COPD ) . The objective of this paper was to determine the effect on healthcare-utilization of an active implementation model for a disease-management-programme for patients with one of the major multimorbidity diseases , COPD . Methods The st and ard implementation of a new disease-management-programme for COPD was ongoing during the study -period from November 2008 to November 2010 in the Central Denmark Region . We wanted to test a strategy using Breakthrough Series , academic detailing and lists of patients with COPD . It targeted GPs and three hospitals serving approx . 60,000 inhabitants aged 35 or older and included interventions directed at professionals , organisations and patients . The study was a non-blinded block- and cluster-r and omised controlled trial with GP- practice s as the unit of r and omisation . In Ringkoebing-Skjern Municipality , Denmark , 16 GP- practice s involving 38 GPs were r and omised to either the intervention-group or the control-group . A comparable neighbouring municipality acted as an external-control-group which included nine GP- practice s with 25 GPs . An algorithm based on health-registry- data on lung-related contacts to the healthcare-system identified 2,736 patients who were alive at the end of the study -period . The population included in this study counted 1,372 ( 69.2 % ) patients who responded to the baseline question naire and confirmed their COPD diagnosis ; 458 ( 33.4 % ) patients were from the intervention-group , 376 ( 27.4 % ) from the control-group and 538(39.2 % ) from the external-control-group . The primary outcome was adherence to the disease-management-programme measured at patient-level by use of specific services from general practice . Secondary outcomes were use of out-of-hours-services , outpatient-clinic , and emergency-department and hospital-admissions . Results The intervention practice s provided more planned preventive consultations , additional preventive consultations and spirometries than non-intervention practice s. A comparison of the development in the intervention practice s with the development in the control- practice s showed that the intervention result ed in more planned preventive-consultations , fewer conventional consultations and fewer patients admitted without a lung-related-diagnosis . Conclusions Use of the active implementation model for the disease-management-programme for COPD changed the healthcare utilization in accordance with the programme . Trial registration Clinical trials.gov identifier : NCT01228708 The authors estimated the costs and cost savings of implementing a program of mailed practice guidelines and single-visit individual and group academic detailing interventions in a r and omized controlled trial to improve the use of antihypertensive medications . Analyses took the perspective of the payer . The total costs of the mailed guideline , group detailing , and individual detailing interventions were estimated at 1000 dollars , 5500 dollars , and 7200 dollars , respectively , corresponding to changes in the average daily per person drug costs of -0.0558 dollars ( 95 % confidence interval , -0.1365 dollars to 0.0250 dollars ) in the individual detailing intervention and -0.0001 dollars ( 95 % confidence interval , -0.0803 dollars to 0.0801 dollars ) in the group detailing intervention , compared with the mailed intervention . For all patients with incident hypertension in the individual detailing arm , the annual total drug cost savings were estimated at 21,711 dollars ( 95 % confidence interval , 53,131 dollars savings to 9709 dollars cost increase ) . Information on costs of academic detailing could assist with health plan decision making in developing interventions to improve prescribing OBJECTIVE This report describes findings from a r and omized controlled trial of an intervention to increase colorectal cancer ( CRC ) screening in primary care practice s in Appalachian Kentucky . METHODS Sixty-six primary care practice s were r and omized to early or delayed intervention groups . The intervention was provided at practice s using academic detailing , a method of education where providers receive information on a specific topic through personal contact . Data were collected in cross-sectional surveys of medical records at baseline and six months post-intervention . RESULTS A total of 3844 medical records were review ed at baseline and 3751 at the six-month follow-up . At baselines , colonoscopy was recommended more frequently ( 43.4 % ) than any other screening modality , followed by fecal occult blood testing ( 18.0 % ) , flexible sigmoidoscopy ( 0.4 % ) , and double-contrast barium enema ( 0.3 % ) . Rates of documented screening results were higher for all practice s at the six-month follow-up for colonoscopy ( 31.8 % vs 29.6 % ) and fecal occult blood testing ( 12.2 % vs 11.2 % ) . For early intervention practice s that recommended screening , colonoscopy rates increased by 15.7 % at six months compared to an increase of 2.4 % in the delayed intervention practice s ( p=.01 ) . CONCLUSIONS Using academic detailing to reach rural primary care providers with a CRC screening intervention was associated with an increase in colonoscopy BACKGROUND Physician adherence to National Cholesterol Education Program clinical practice guidelines has been poor . METHODS We recruited 68 primary care family and internal medicine practice s ; 66 were r and omly allocated to a study arm ; 5 practice s withdrew , result ing in 29 receiving the Third Adult Treatment Panel ( ATP III ) intervention and 32 receiving an alternative intervention focused on the Seventh Report of the Joint National Committee on the Prevention , Detection , Evaluation , and Treatment of High Blood Pressure ( JNC-7 ) . The ATP III providers received a personal digital assistant providing the Framingham risk scores and ATP III-recommended treatment . All practice s received copies of each clinical practice guideline , an introductory lecture , 1 performance feedback report , and 4 visits for intervention-specific academic detailing . Data were abstract ed at 61 practice s from r and om sample s of medical records of patients treated from June 1 , 2001 , through May 31 , 2003 ( baseline ) , and from May 1 , 2004 , through April 30 , 2006 ( follow-up ) . The proportion screened with subsequent appropriate decision making ( primary outcome ) was calculated . Generalized estimating equations were used to compare results by arm , accounting for clustering of patients within practice s. RESULTS We examined 5057 baseline and 3821 follow-up medical records . The screening rate for lipid levels increased from 43.6 % to 49.0 % ( ATP III practice s ) and from 40.1 % to 50.8 % ( control practice s ) ( net difference , -5.3 % [ P = .22 ] ) . Appropriate management of lipid levels decreased slightly ( 73.4 % to 72.3 % ) in ATP III practice s and more markedly ( 79.7 % to 68.9 % ) in control practice s. The net change in appropriate management favored the intervention ( + 9.7 % ; 95 % confidence interval [ CI ] , 2.8%-16.6 % [ P < .01 ] ) . Appropriate drug prescription within 4 months decreased in both arms ( 38.8 % to 24.8 % in ATP III practice s and 45.3 % to 24.1 % in control practice s ; net change , + 7.2 % [ P = .37 ] ) Overtreatment declined from 6.6 % to 3.9 % in ATP III and rose from 4.2 % to 6.4 % in control practice s ( net change , -4.9 % [ P = .01 ] ) . CONCLUSIONS A multifactor intervention including personal digital assistant-based decision support may improve primary care physician adherence to the ATP III guidelines . Trial Registration clinical trials.gov Identifier : NCT00224848 PURPOSE Potentially inappropriate prescribing ( PIP ) is common in older people and can result in increased morbidity , adverse drug events , and hospitalizations . The OPTI-SCRIPT study ( Optimizing Prescribing for Older People in Primary Care , a cluster-r and omized controlled trial ) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care . METHODS We conducted a cluster-r and omized controlled trial among 21 general practitioner practice s and 196 patients with PIP . Intervention participants received a complex , multifaceted intervention incorporating academic detailing ; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative-treatment options ; and tailored patient information leaflets . Control practice s delivered usual care and received simple , patient-level PIP feedback . Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions . We performed intention-to-treat analysis using r and om-effects regression . RESULTS All 21 practice s and 190 patients were followed . At intervention completion , patients in the intervention group had significantly lower odds of having PIP than patients in the control group ( adjusted odds ratio = 0.32 ; 95 % CI , 0.15–0.70 ; P = .02 ) . The mean number of PIP drugs in the intervention group was 0.70 , compared with 1.18 in the control group ( P = .02 ) . The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion , but this difference was not significant ( incidence rate ratio = 0.71 ; 95 % CI , 0.50–1.02 ; P = .49 ) . The intervention was effective in reducing proton pump inhibitor prescribing ( adjusted odds ratio = 0.30 ; 95 % CI , 0.14–0.68 ; P = .04 ) . CONCLUSIONS The OPTI-SCRIPT intervention incorporating academic detailing with a pharmacist , and a review of medicines with web-based pharmaceutical treatment algorithms , was effective in reducing PIP , particularly in modifying prescribing of proton pump inhibitors , the most commonly occurring PIP drugs nationally BACKGROUND Fax referral programs quickly and economically can link smokers ' visiting primary care clinics to state-based telephone quitlines . Yet , it is unclear how to optimize use of this strategy . PURPOSE To evaluate the potential of enhanced academic detailing in clinics ( i.e. , on-site training , technical assistance , and performance feedback ) to boost utilization of a fax referral program called Fax to Quit . DESIGN Participants were r and omized to one of two intervention conditions . SETTING / PARTICIPANTS Participants were drawn from 49 primary care clinics in southeastern Wisconsin . The sample size was based on a power analysis in which the control intervention condition was estimated to generate 0.5 referrals/clinic/month and the experimental condition 2.0 referrals/clinic/month . INTERVENTIONS One of two fax referral program interventions was administered : the control condition Fax to Quit-Only ( F2Q-Only ) or the experimental condition Fax to Quit plus Enhanced Academic Detailing ( F2Q+EAD ) . MAIN OUTCOME MEASURES Clinic- and clinician-specific referral and quality referral rates ( those result ing in quitline enrollment ) were measured for 13 months post-intervention , starting in March 2009 . RESULTS Mean number of post-intervention referrals/clinician to the Wisconsin Tobacco Quitline was 5.6 times greater for F2Q+EAD ( 8.5 , SD=7.0 ) compared to F2Q-Only ( 1.6 , SD=3.6 , p<0.001 ) . The F2Q+EAD ( 4.8 , SD=4.1 ) condition produced a greater mean number of quality referrals/clinician than did the F2Q-Only ( 0.86 , SD=1.8 , p<0.001 ) condition . Data were analyzed in 2010 . CONCLUSIONS Enhanced academic detailing , which included on-site training , technical assistance , and performance feedback , increased the number of referrals more than fivefold over a fax referral program implemented without such enhanced academic detailing . TRIAL REGISTRATION This study is registered at Clinical trials.gov NCT00989755 Background Clinical practice guidelines ( CPGs ) recommend universal prenatal screening for Group B Streptococcus ( GBS ) to identify c and i date s for intrapartum antibiotic prophylaxis to prevent early onset neonatal GBS infection . Interventions to promote physician adherence to these guidelines are imperative . This study examined the effectiveness of academic detailing ( AD ) of obstetricians , compared with CPG mailshot and no intervention , on the screening of pregnant women for GBS . Methods A r and omized controlled clinical trial was conducted in the medical cooperative of Porto Alegre , Brazil . All obstetricians who assisted in a delivery covered by private health insurance managed by the cooperative in the 3 months preceding the study ( n = 241 ) were invited to participate . The obstetricians were r and omized to three groups : direct mail ( DM , n = 76 ) , AD ( n = 76 ) and control ( C , n = 89 , no intervention ) . Those in the DM group were sent guidelines on GBS . The AD group received the guidelines and an educational visit detailing the guidelines , which was conducted by a trained physician . Data on obstetrician age , gender , time since graduation , whether patients received GBS screening during pregnancy , and obstetricians who requested screening were collected for all participant obstetricians for 3 months before and after the intervention , using data base from the private health insurance information system . Results Three months post-intervention , the data showed that the proportion of pregnant women screened for GBS was higher in the AD group ( 25.4 % ) than in the DM ( 15.9 % ) and C ( 17.7 % ) groups ( P = 0.023 ) . Similar results emerged when the three groups were taken as a cluster ( pregnant women and their obstetricians ) , but the difference was not statistically significant ( Poisson regression , P = 0.108 ) . Additionally , when vaginal deliveries were analyzed separately , the proportion screened was higher in the AD group ( 75 % ) than in the DM group ( 41.9 % ) and the C group ( 30.4 % ) ( chi-square , P < 0.001 ) . Conclusions The results suggest that AD increased the prevalence of GBS screening in pregnant women in this population BACKGROUND Out reach facilitation is design ed to promote uptake of evidence -based guidelines . There is evidence indicating that outreach facilitation can be effective in improving implementation of preventive care in GPs ' offices . In this trial , we test a modified version of an outreach facilitation intervention . OBJECTIVE To evaluate whether a comprehensive preventive intervention program using outreach facilitators improves preventive care delivery . DESIGN Match-paired , cluster-r and omized controlled trial . SETTING Fee-for-service primary care practice s in Eastern Ontario , Canada , at a time of physician shortage . PARTICIPANTS Volunteer sample of 54 primary care practice s. MAIN OUTCOME MEASURES Mean difference between trial arms in practice s ' delivery of preventive manoeuvres , measured by preventive performance indices estimated from chart review s and patient survey data . RESULTS No difference was detected between the trial 's arms for the primary outcome 's overall prevention index [ 2.0 % ; 95 % confidence interval ( CI ) -3.2 to 7.3 ; P = 0.44 ] . A small significant difference between the arms was detected for the secondary outcome 's overall prevention index ( 2.8 % ; 95 % CI 0.7 - 4.8 ; P = 0.01 ) . CONCLUSION In contrast to similar facilitation trials , this outreach facilitation program did not produce improvements in the delivery of preventive care . This lack of effect may be due to differences in the intervention and context , or the practice 's limited capacity to change . Our intervention simultaneously facilitated a high number of manoeuvres , blinded facilitators and physicians to the targeted tests and had a relatively short intervention period and large number of practice s assigned per facilitator . Changes in the primary care service model in Ontario at the time of the trial could have also washed out the intervention effect Introduction Information on benefits and risks of drugs is a key element affecting doctors ’ prescribing decisions . Outreach visits promoting independent information have proved moderately effective in changing prescribing behaviours . Objectives Testing the short and long-term effectiveness on general practitioners ’ prescribing of small groups meetings led by pharmacists . Methods Two cluster open r and omised controlled trials ( RCTs ) were carried out in a large scale NHS setting . Ad hoc prepared evidence based material were used considering a therapeutic area approach - TEA , with information material s on osteoporosis or prostatic hyperplasia - and a single drug oriented approach - SIDRO , with information material s on me-too drugs of 2 different classes : barnidipine or prulifloxacin . In each study , all 115 Primary Care Groups in a Northern Italy area ( 2.2 million inhabitants , 1737 general practitioners ) were r and omised to educational small groups meetings , in which available evidence was provided together with drug utilization data and clinical scenarios . Main outcomes were changes in the six-months prescription of targeted drugs . Longer term results ( 24 and 48 months ) were also evaluated . Results In the TEA trial , one of the four primary outcomes showed a reduction ( prescription of alfuzosin compared to tamsulosin and terazosin in benign prostatic hyperplasia : prescribing ratio −8.5 % , p = 0.03 ) . Another primary outcome ( prescription of risedronate ) showed a reduction at 24 and 48 months ( −7.6 % , p = 0.02 ; and −9,8 % , p = 0.03 ) , but not at six months ( −5.1 % , p = 0.36 ) . In the SIDRO trial both primary outcomes showed a statistically significant reduction ( prescription of barnidipine −9.8 % , p = 0.02 ; prescription of prulifloxacin −11.1 % , p = 0.04 ) , which persisted or increased over time . Interpretation These two cluster RCTs showed the large scale feasibility of a complex educational program in a NHS setting , and its potentially relevant long-term impact on prescribing habits , in particular when focusing on a single drug . National Health systems should invest in independent drug information programs . Trial Registration Controlled-Trials.com IS RCT BACKGROUND Older patients are at particular risk for adverse drug reactions . In older people , interventions targeting potentially inappropriate prescriptions ( PIPs ) are considered important measures to minimise drug-related harm , especially in the general practice setting where most prescriptions for older patients are issued . AIM To study the effects of a multifaceted educational intervention on GPs ' PIPs for older patients . DESIGN AND SETTING This was a cluster r and omised , educational intervention study in Norwegian general practice . Pre- study data were captured from January 2005 to December 2005 and post- study data from June 2006 to June 2007 . The educational intervention was carried out from January 2006 to June 2006 . METHOD Eighty continuing medical education ( CME ) groups ( 465 GPs ) were r and omised to receive the educational intervention on GPs ' PIPs for older patients ( 41 CME groups ; 256 GPs ) or another educational intervention ( 39 CME groups ; 209 GPs ) ; these two groups acted as controls for each other . GPs ' prescription data from before and after the intervention were assessed against a list of 13 explicit PIP criteria for patients aged ≥70 years . In the CME groups , trained GPs carried out an educational programme , including an audit , focusing on the 13 criteria and their rationale . RESULTS A total of 449 GPs ( 96.6 % ) completed the study ; 250 in the intervention group and 199 in the control group . After adjusting for baseline differences and clustering effects , a reduction relative to baseline of 10.3 % ( 95 % confidence interval = 5.9 to 15.0 ) PIPs per 100 patients aged ≥70 years was obtained . CONCLUSION Educational outreach visits with feedback and audit , using GPs as academic detailers in GPs ' CME groups , reduced PIPs for older patients aged ≥70 years in general practice Purpose : In 2004 only 68 % of women in Oklahoma over the age of 40 reported having a mammogram in the past 2 years , compared with 75 % nationally . Strategies to improve mammography rates have been numerous but have generally included single strategies , such as physician education , practice audit and feedback , and reminders ; flow sheets and results have been mixed . The purpose of this r and omized controlled trial was to determine the impact of a practice facilitator and “ best practice ” interventions on mammography rates in a practice -based research network . Methods : A total of 16 practice s participated ; 8 were assigned to intervention and 8 to usual care . Pre- and post-audits of mammography rates were conducted . Intervention practice s received feedback with benchmarking , academic detailing , and the assistance of a practice enhancement assistant to help with practice re design over a 9-month period . Results : The groups differed significantly for both the proportion of mammograms offered to eligible patients ( P = .043 ) and for the proportion of patients with current mammograms ( P < .015 ) . For the control group , 38 % of eligible women were offered a mammogram and 202 ( 35 % of those eligible ) actually did have documentation that a mammogram had been performed . Fifty-three percent of the eligible patients in the intervention group were offered a mammogram and 52 % of those eligible ( n = 332 ) did have documentation in the chart that the mammogram had been completed . Conclusion : The results suggest that these interventions can improve mammography rates in a range of practice setting s. These findings are consistent with other studies that have tested multicomponent interventions Objective A major problem with inappropriate use of antibiotics is the emergence of resistance . Thus , cost-effective interventional strategies are required to improve their use . This study aim ed to evaluate the effect of multifaceted interventions on prescribing practice s of antibiotics in health centers of Khartoum State , Sudan . Methods Twenty health centers were r and omly assigned to receive : ( 1 ) no intervention ; ( 2 ) audit and feedback ; ( 3 ) audit and feedback + seminar ; or ( 4 ) audit and feedback + academic detailing . A total of 1,800 patient encounters , 30 from each health center , were r and omly collected . The total number of encounters with antibiotics prescribed were determined in each health center and they were evaluated with regard to antibiotic choice , dose and duration of therapy before the study and at 1 and 3 months post-intervention . Results In comparison to the control group , the prescriber targeted interventions involving audit and feedback , together with academic detailing ( 4 ) , reduced the mean number of encounters with an antibiotic prescribed by 6.3 and 7.7 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . In addition , the mean number of encounters with an inappropriate antibiotic with respect to diagnosis , doses and / or duration of therapy was reduced by 5.3 and 5.9 ( p<0.001 ) at 1 and 3 months post-intervention , respectively . For audit and feedback together with seminars ( 3 ) and for audit and feedback alone ( 2 ) , the corresponding reductions were 5.3 , 7.1 , 4.4 and 5.1 ( p<0.001 ) and 1.4 , 2.8 , 1.8 and 1.9 ( p>0.05 ) , respectively . Conclusion Inappropriate prescribing patterns of antibiotics in health centers of Khartoum State , Sudan , are alarmingly high . Multifaceted interventions involving audit and feedback combined with either academic detailing or seminars appear more effective in changing prescribing practice s of antibiotics than audit and feedback alone Background : Previous research has found that wellness visits , recall and reminder systems , and st and ing orders are associated with higher rates of delivery of preventive services in primary care practice s. However , there is little information about how to help practice s implement these processes . Methods : A 6-month r and omized , controlled trial comparing a multicomponent quality improvement intervention to feedback and benchmarking . One clinician/nurse team from each of 24 practice s was r and omly assigned to one of 2 study arms . Intervention practice s received performance feedback , peer-to-peer education ( academic detailing ) , a practice facilitator , and computer ( information technology ) support . Implementation of the 3 targeted processes was determined by a blinded 3-clinician panel that review ed transcribed clinician interviews before and after intervention using performance definitions . Rates of delivery of selected preventive services were determined by chart audit . Results : Intervention practice s implemented more of the processes than control practice s overall ( P = .003 ) , for adults ( P = .05 ) , and for children ( P = .04 ) . They were also more likely to implement at least one of the processes for children ( P = .04 ) and to implement st and ing orders for either children or adults ( P = .02 ) . Mammography rates increased significantly . Neither clinician and practice characteristics nor clinician readiness to change predicted implementation . Conclusions : A multicomponent implementation strategy consisting of feedback , benchmarking , academic detailing , facilitation , and IT support increased implementation of evidence -based processes for delivering preventive services to a greater extent than performance feedback and benchmarking alone PURPOSE We investigated 3 approaches for implementing the Chronic Care Model to improve diabetes care : ( 1 ) practice facilitation over 6 months using a reflective adaptive process ( RAP ) approach ; ( 2 ) practice facilitation for up to 18 months using a continuous quality improvement ( CQI ) approach ; and ( 3 ) providing self-directed ( SD ) practice s with model information and re sources , without facilitation . METHODS We conducted a cluster-r and omized trial , called Enhancing Practice , Improving Care ( EPIC ) , that compared these approaches among 40 small to midsized primary care practice s. At baseline and 9 months and 18 months after enrollment , we assessed practice diabetes quality measures from chart audits and Practice Culture Assessment scores from clinician and staff surveys . RESULTS Although measures of the quality of diabetes care improved in all 3 groups ( all P < .05 ) , improvement was greater in CQI practice s compared with both SD practice s ( P < .0001 ) and RAP practice s ( P < .0001 ) ; additionally , improvement was greater in SD practice s compared with RAP practice s ( P < .05 ) . In RAP practice s , Change Culture scores showed a trend toward improvement at 9 months ( P = .07 ) but decreased below baseline at 18 months ( P < .05 ) , while Work Culture scores decreased from 9 to 18 months ( P < .05 ) . Both scores were stable over time in SD and CQI practice s. CONCLUSIONS Traditional CQI interventions are effective at improving measures of the quality of diabetes care , but may not improve practice change and work culture . Short-term practice facilitation based on RAP principles produced less improvement in quality measures than CQI or SD interventions and also did not produce sustained improvements in practice culture PURPOSE The aim of this study is to evaluate the effectiveness of academic detailing ( AD ) plus postal prescribing feedback versus postal prescribing feedback alone in reducing : ( i ) the overall rate of antibiotic ; and ( ii ) proportion of second-line antibiotic prescribing . In addition , the cost-effectiveness of an outreach prescriber adviser service versus a postal prescribing feedback service was evaluated . METHODS Volunteer general practitioner practice s ( n = 98 ) were r and omized to receive prescribing feedback via postal bulletin ( PB ) ( n = 50 ) or academic detailing plus postal bulletin ( AD ) ( n = 48 ) . Data analysis was based on the HSE- primary care reimbursement service ( HSE-PCRS ) prescribing data base . Regression ( beta ) coefficients , indicating proportion change in prescribing per month , and 95 % confidence intervals ( CIs ) are presented . The cost-effectiveness ratio was calculated from the total cost of the intervention divided by percentage change in antibiotic prescribing in AD versus PB group . RESULTS Immediately post intervention PB ( beta = -0.02 , 95 % CI -0.04 , -0.001 ) and AD ( beta = -0.02 , 95 % CI -0.03 , -0.001 ) practice s significantly decreased overall antibiotic prescribing . Second-line antibiotic prescribing was also significantly decreased by 2 - 3 % in both groups . However , there were no significant differences in antibiotic prescribing between the r and omized groups in the immediate or long-term post-intervention period . In the cost-effectiveness analysis a postal prescribing feedback service would cost euro 88 per percentage change in prescribing practice compared with euro 778 for a prescriber adviser service . CONCLUSION Prescribing feedback significantly reduced overall and second-line antibiotic prescribing , but academic detailing was not significantly more effective than postal bulletin in changing antibiotic prescribing practice OBJECTIVE At-risk drinking and alcohol use disorders are common in primary care and may adversely affect the treatment of patients with diabetes and /or hypertension . The purpose of this article is to report the impact of dissemination of a practice -based quality improvement approach ( Practice Partner Research Network-Translating Research into Practice [ PPRNet-TRIP ] ) on alcohol screening , brief intervention for at-risk drinking and alcohol use disorders , and medications for alcohol use disorders in primary care practice s. METHOD Nineteen primary care practice s from 15 states representing 26,005 patients with diabetes and /or hypertension participated in a group-r and omized trial ( early intervention vs. delayed intervention ) . The 12-month intervention consisted of practice site visits for academic detailing and participatory planning and network meetings for " best practice " dissemination . RESULTS At the end of Phase 1 , eligible patients in early-intervention practice s were significantly more likely than patients in delayed-intervention practice s to have been screened ( odds ratio [ OR ] = 3.30 , 95 % CI [ 1.15 , 9.50 ] ) and more likely to have been provided a brief intervention ( OR = 6.58 , 95 % CI [ 1.69 , 25.7 ] . At the end of Phase 2 , patients in delayed-intervention practice s were more likely than at the end of Phase 1 to have been screened ( OR = 5.18 , 95 % CI [ 4.65 , 5.76 ] ) and provided a brief intervention ( OR = 1.80 , 95 % CI [ 1.31 , 2.47 ] ) . Early-intervention practice s maintained their screening and brief intervention performance during Phase 2 . Medication for alcohol use disorders was prescribed infrequently . CONCLUSIONS PPRNet-TRIP is effective in improving and maintaining improvement in alcohol screening and brief intervention for patients with diabetes and /or hypertension in primary care setting RATIONALE Because of high mortality , end-of-life care is an important component of intensive care . OBJECTIVES We evaluated the effectiveness of a quality -improvement intervention to improve intensive care unit ( ICU ) end-of-life care . METHODS We conducted a cluster-r and omized trial r and omizing 12 hospitals . The intervention targeted clinicians with five components : clinician education , local champions , academic detailing , clinician feedback of quality data , and system supports . Outcomes were assessed for patients dying in the ICU or within 30 hours of ICU discharge using surveys and medical record review . Families completed Quality of Dying and Death ( QODD ) and satisfaction surveys . Nurses completed the QODD . Data were collected during baseline and follow-up at each hospital ( May 2004 to February 2008 ) . We used robust regression models to test for intervention effects , controlling for site , patient , family , and nurse characteristics . MEASUREMENTS AND MAIN RESULTS All hospitals completed the trial with 2,318 eligible patients and target sample sizes obtained for family and nurse surveys . The primary outcome , family-QODD , showed no change with the intervention ( P = 0.33 ) . There was no change in family satisfaction ( P = 0.66 ) or nurse-QODD ( P = 0.81 ) . There was a nonsignificant increase in ICU days before death after the intervention ( hazard ratio = 0.9 ; P = 0.07 ) . Among patients undergoing withdrawal of mechanical ventilation , there was no change in time from admission to withdrawal ( hazard ratio = 1.0 ; P = 0.81 ) . CONCLUSIONS We found this intervention was associated with no improvement in quality of dying and no change in ICU length of stay before death or time from ICU admission to withdrawal of life-sustaining measures . Improving ICU end-of-life care will require interventions with more direct contact with patients and families . Clinical trial registered with www . clinical trials.gov ( NCT00685893 ) BACKGROUND Computerized decision support reduces medication errors in in patients , but limited evidence supports its effectiveness in reducing the coprescribing of interacting medications , especially in the outpatient setting . The usefulness of academic detailing to enhance the effectiveness of medication interaction alerts also is uncertain . METHODS This study used an interrupted time series design . In a health maintenance organization with an electronic medical record , we evaluated the effectiveness of electronic medical record alerts and group academic detailing to reduce the coprescribing of warfarin and interacting medications . Participants were 239 primary care providers at 15 primary care clinics and 9910 patients taking warfarin . All 15 clinics received electronic medical record alerts for the coprescription of warfarin and 5 interacting medications : acetaminophen , nonsteroidal anti-inflammatory medications , fluconazole , metronidazole , and sulfamethoxazole . Seven clinics were r and omly assigned to receive group academic detailing . The primary outcome , the interacting prescription rate ( ie , the number of coprescriptions of warfarin-interacting medications per 10 000 warfarin users per month ) , was analyzed with segmented regression models , controlling for preintervention trends . RESULTS At baseline , nearly a third of patients had an interacting prescription . Coinciding with the alerts , there was an immediate and continued reduction in the warfarin-interacting medication prescription rate ( from 3294.0 to 2804.2 ) , result ing in a 14.9 % relative reduction ( 95 % confidence interval , -19.5 to -10.2 ) at 12 months . Group academic detailing did not enhance alert effectiveness . CONCLUSIONS This study , using a strong and quasi-experimental design in ambulatory care , found that medication interaction alerts modestly reduced the frequency of coprescribing of interacting medications . Additional efforts will be required to further reduce rates of inappropriate prescribing of warfarin with interacting drugs BACKGROUND Academic detailing utilizes educators trained in social marketing to conduct one-on-one visits with physicians using evidence -based data . Academic detailing programs have improved physician 's prescribing behaviors ; however , the feasibility of large-scale programs across a large , geographically disperse state is unclear . METHODS The study team collaborated with a state-run pharmacy benefits program for low-income elderly in a trial to improve osteoporosis management . Community-practicing physicians who saw a minimum of 25 patients enrolled in the benefits program were r and omized to receive academic detailing or not . Fourteen educators were trained in the principles of academic detailing as well as osteoporosis epidemiology , diagnosis , and treatment . From September 2003 to January 2004 , they attempted to meet with physicians or an allied health professional to discuss osteoporosis and fracture prevention . RESULTS The physician population was 356 and 148 ( 41.6 % ) visits were completed-100 with physicians , 38 with allied health professionals , and 10 with both the physician and an allied health professional . In mixed multivariable models , there were no physician characteristics associated with completed encounters , including gender , training , geographic location , years since medical school , and number of study patients ( all p-values > 0.11 ) . The detailer 's gender , professional training , and professional experience were not statistically significant correlates of completed encounters ( all p-values > 0.28 ) . Number of years since a detailer 's professional training was a predictor of a completed encounter , OR = 1.43 per 5 years ( 95%CI 1.05 , 1.96 ) . CONCLUSIONS A moderate rate of completed encounters was achieved . There was only one predictor of completed encounters OBJECTIVES We tested a modified Network for the Improvement of Addiction Treatment ( NIATx ) process improvement model to implement improved HIV services ( prevention , testing , and linkage to treatment ) for offenders under correctional supervision . METHODS As part of the Criminal Justice Drug Abuse Treatment Studies , Phase 2 , the HIV Services and Treatment Implementation in Corrections study conducted 14 cluster-r and omized trials in 2011 to 2013 at 9 US sites , where one correctional facility received training in HIV services and coaching in a modified NIATx model and the other received only HIV training . The outcome measure was the odds of successful delivery of an HIV service . RESULTS The results were significant at the .05 level , and the point estimate for the odds ratio was 2.14 . Although overall the results were heterogeneous , the experiments that focused on implementing HIV prevention interventions had a 95 % confidence interval that exceeded the no-difference point . CONCLUSIONS Our results demonstrate that a modified NIATx process improvement model can effectively implement improved rates of delivery of some types of HIV services in correctional environments PURPOSE Guideline implementation in primary care has proven difficult . Although external assistance through performance feedback , academic detailing , practice facilitation ( PF ) , and learning collaboratives seems to help , the best combination of interventions has not been determined . METHODS In a cluster r and omized trial , we compared the independent and combined effectiveness of PF and local learning collaboratives ( LLCs ) , combined with performance feedback and academic detailing , with performance feedback and academic detailing alone on implementation of the National Heart , Lung and Blood Institute ’s Asthma Guidelines . The study was conducted in 3 primary care practice -based research networks . Medical records of patients with asthma seen during pre- and postintervention periods were abstract ed to determine adherence to 6 guideline recommendations . McNemar ’s test and multivariate modeling were used to evaluate the impact of the interventions . RESULTS Across 43 practice s , 1,016 patients met inclusion criteria . Overall , adherence to all 6 recommendations increased ( P ≤.002 ) . Examination of improvement by study arm in unadjusted analyses showed that practice s in the control arm significantly improved adherence to 2 of 6 recommendations , whereas practice s in the PF arm improved in 3 , practice s in the LLCs improved in 4 , and practice s in the PF + LLC arm improved in 5 of 6 recommendations . In multivariate modeling , PF practice s significantly improved assessment of asthma severity ( odds ratio [ OR ] = 2.5 , 95 % CI , 1.7–3.8 ) and assessment of asthma level of control ( OR = 2.3 , 95 % CI , 1.5–3.5 ) compared with control practice s. Practice s assigned to LLCs did not improve significantly more than control practice s for any recommendation . CONCLUSIONS Addition of PF to performance feedback and academic detailing was helpful to practice s attempting to improve adherence to asthma guidelines |
12,846 | 20,137,879 | Metaregression to adjust for age imbalance , study design , and pathology did not material ly change the results .
Current data from nonr and omized studies suggest that TEVAR may reduce early death , paraplegia , renal insufficiency , transfusions , reoperation for bleeding , cardiac complications , pneumonia , and length of stay compared with open surgery . | OBJECTIVES The purpose of this study was to determine whether thoracic endovascular aortic repair ( TEVAR ) reduces death and morbidity compared with open surgical repair for descending thoracic aortic disease .
BACKGROUND The role of TEVAR versus open surgery remains unclear .
Metaregression can be used to maximally inform adoption of new technologies by utilizing evidence from existing trials . | INTRODUCTION The purpose of this American Association for the Surgery of Trauma multicenter study is to assess the early efficacy and safety of endovascular stent grafts ( SGs ) in traumatic thoracic aortic injuries and compare outcomes with the st and ard operative repair ( OR ) . PATIENTS Prospect i ve , multicenter study . Data for the following were collected : age , blood pressure , and Glasgow Coma Scale ( GCS ) at admission , type of aortic injury , injury severity score , abbreviate injury scale ( AIS ) , transfusions , survival , ventilator days , complications , and intensive care unit and hospital days . The outcomes between the two groups ( open repair or SG ) were compared , adjusting for presence of critical extrathoracic trauma ( head , abdomen , or extremity AIS > 3 ) , GCS score < /=8 , systolic blood pressure < 90 mm Hg , and age > 55 years . Separate multivariable analysis was performed , one for patients without and one for patients with associated critical extrathoracic injuries ( head , abdomen , or extremity AIS > 3 ) , to compare the outcomes of the two therapeutic modalities adjusting for hypotension , GCS score < /=8 , and age > 55 years . RESULTS One hundred ninety-three patients met the criteria for inclusion . Overall , 125 patients ( 64.9 % ) were selected for SG and 68 ( 35.2 % ) for OR . SG was selected in 71.6 % of the 74 patients with major extrathoracic injuries and in 60.0 % of the 115 patients with no major extrathoracic injuries . SG patients were significantly older than OR patients . Overall , 25 patients in the SG group ( 20.0 % ) developed 32 device-related complications . There were 18 endoleaks ( 14.4 % ) , 6 of which needed open repair . Procedure-related paraplegia developed in 2.9 % in the OR and 0.8 % in the SG groups ( p = 0.28 ) . Multivariable analysis adjusting for severe extrathoracic injuries , hypotension , GCS , and age , showed that the SG group had a significantly lower mortality ( adjusted odds ratio : 8.42 ; 95 % CI : [ 2.76 - 25.69 ] ; adjusted p value < 0.001 ) , and fewer blood transfusions ( adjusted mean difference : 4.98 ; 95 % CI : [ 0.14 - 9.82 ] ; adjusted p value = 0.046 ) than the OR group . Among the 115 patients without major extrathoracic injuries , higher mortality and higher transfusion requirements were also found in the OR group ( adjusted odds ratio for mortality : 13.08 ; 95 % CI [ 2.53 - 67.53 ] , adjusted p value = 0.002 and adjusted mean difference in transfusion units : 4.45 ; 95 % CI [ 1.39 - 7.51 ] ; adjusted p value = 0.004 ) . Among the 74 patients with major extrathoracic injuries , significantly higher mortality and pneumonia rate were found in the OR group ( adjusted p values 0.04 and 0.03 , respectively ) . Multivariate analysis showed that centers with high volume of endovascular procedures had significantly fewer systemic complications ( adjusted p value 0.001 ) , fewer local complications ( adjusted p value p = 0.033 ) , and shorter hospital lengths of stay ( adjusted p value 0.005 ) than low-volume centers . CONCLUSIONS Most surgeons select SG for traumatic thoracic aortic ruptures , irrespective of associated injuries , injury severity , and age . SG is associated with significantly lower mortality and fewer blood transfusions , but there is a considerable risk of serious device-related complications . There is a major and urgent need for improvement of the available endovascular devices PURPOSE This trial evaluated the safety and effectiveness of thoracic endovascular aortic repair ( TEVAR ) with a contemporary endograft system compared with open surgical repair ( open ) of descending thoracic aortic aneurysms and large ulcers . METHODS Forty-two international trial sites enrolled 230 subjects with descending thoracic aortic aneurysms or ulcers . The study compared 160 TEVAR subjects treated with the Zenith TX2 Endovascular Graft ( William Cook Europe , ApS , Bjaeverskov , Denmark ) with 70 open subjects . Subjects were evaluated preprocedure , predischarge , 1 , 6 , and 12 months , and yearly through 5 years with medical examination , laboratory testing , chest radiographs , and computed tomography scans . Mortality rates , prespecified severe morbidity composite index , major morbidity , clinical utility , aneurysm rupture , and secondary interventions were compared . The TEVAR subjects were evaluated by a core laboratory for device performance , including change in aneurysm size , endoleak , migration , and device integrity . RESULTS The 30-day survival rate was noninferior ( P < .01 ) for the TEVAR group compared with the open group ( 98.1 % vs 94.3 % ) . The severe morbidity composite index was lower for TEVAR ( 0.2 + /- 0.7 vs 0.7 + /- 1.2 ; P < .01 ) . Cumulative major morbidity scores were significantly lower at 30 days for the TEVAR group compared with the open group ( 1.3 + /- 3.0 vs 2.9 + /- 3.6 , P < .01 ) . The TEVAR patients had fewer cardiovascular , pulmonary , and vascular adverse events , although neurologic events were not significantly different . Clinical utility for the TEVAR patients was superior to that of the open patients . No ruptures or conversions occurred in the first year . Reintervention rates were similar in both groups . At 12 months , aneurysm growth was identified in 7.1 % ( 8/112 ) , endoleak in 3.9 % ( 4/103 ) , migration ( > 10 mm ) in 2.8 % ( 3/107 ) , and other device issues were rare . None of the patients with migration experienced endoleak , aneurysm growth , or required a secondary intervention . CONCLUSIONS Thoracic endovascular aortic repair with the TX2 is a safer and effective alternative to open surgical repair for the treatment of anatomically suitable descending thoracic aortic aneurysms and ulcers at 1 year of follow-up . Device performance issues are infrequent , but careful planning and regular follow-up with imaging remain a necessity Despite significant improvements in surgical techniques and perioperative management , the repair of descending thoracic aortic aneurysms remains a challenge with the potential for substantial morbidity and mortality . Over the past several years , buoyed by the technical success of endovascular repair of infrarenal abdominal aortic aneurysms , several case series reports of endovascular stent-graft placement for descending thoracic aortic aneurysms have demonstrated the potential safety and efficacy of this treatment modality . Several single-institution studies have documented promising results with these devices , but without controlled clinical trials , the data are insufficient to determine if thoracic aortic endografts provide equivalent or improved outcomes compared with st and ard open repair . We describe a study design of an ongoing prospect i ve , nonr and omized , multi-institutional , investigational device exemption phase II pivotal clinical trial investigating the safety and effectiveness of the Zenith TX2 thoracic aortic endovascular graft in the elective treatment of patients with descending thoracic aortic aneurysms OBJECTIVE The purpose of this study was to evaluate the safety and efficacy of a novel endovascular graft for elective treatment of infrarenal abdominal aortic aneurysm . The device is a modular bifurcated system with nitinol/exp and ed polytetrafluoroethylene components and a smaller profile than currently approved devices . METHODS In a multicenter , concurrent controlled phase II trial , 334 patients underwent treatment with the Excluder bifurcated endoprosthesis ( test , n = 235 ; W. L. Gore & Associates , Inc , Sunnyvale , Calif ) or with st and ard open repair ( control , n = 99 ) . Preoperative characteristics , perioperative variables , follow-up clinical evaluations , and radiographic examination results through the first 2 years were analyzed with univariable and multivariable statistics . RESULTS Patients in the test group had less blood loss ( 310 + /- 19 mL versus 1590 + /- 124 mL ; P < .0001 ) , fewer homologous transfusions ( 6 % versus 32 % ; P < .0001 ) , and shorter lengths of stay ( 2.0 + /- 0.1 days versus 9.8 + /- 1.4 days ; P < .0001 ) . Early major adverse events were markedly reduced in the test group ( 14 % versus 57 % ; P < .0001 ) , and this difference persisted at 2 years . No difference was seen in survival rate ( P = .13 ) . In the first 2 years , no deployment failure , early conversion , or aneurysm rupture occurred . At the 2-year timepoint , core laboratory read trunk migration in 1 % , limb migration in 1 % , limb narrowing in 1 % , endoleak in 20 % , and aneurysm growth in 14 % . One wire discontinuity ( 0.6 % ) was identified in a discharge film . A 7 % annual reintervention rate was seen in the test group in the first 2 years . SUMMARY The test device is a safe and effective treatment compared with open surgical repair for infrarenal abdominal aortic aneurysm . The most striking benefits are reduced blood loss , fewer complications , and faster recovery . Two-year survival rate was similar OBJECTIVE Results are presented from the first completed multicenter trial directed at gaining approval from the US Food and Drug Administration of endovascular versus open surgical repair of descending thoracic aortic aneurysms . METHODS Between September 1999 and May 2001 , 140 patients with descending thoracic aneurysms were enrolled at 17 sites and evaluated for a Gore TAG Thoracic Endograft . An open surgical control cohort of 94 patients was identified by enrolling historical and concurrent subjects . Patients were assessed before treatment , at treatment , and at hospital discharge and returned for follow-up visits at 1 month , 6 months , and annually thereafter . RESULTS One hundred thirty-seven of 140 patients had successful implantation of the endograft . Perioperative mortality in the endograft versus open surgical control cohort was 2.1 % ( n = 3 ) versus 11.7 % ( n = 11 , P < .001 ) . Thirty-day analysis revealed a statistically significant lower incidence of the following complications in the endovascular cohort versus the surgical cohort : spinal cord ischemia ( 3 % vs 14 % ) , respiratory failure ( 4 % vs 20 % ) , and renal insufficiency ( 1 % vs 13 % ) . The endovascular group had a higher incidence of peripheral vascular complications ( 14 % vs 4 % ) . The mean lengths of intensive care unit stay ( 2.6 + /- 14.6 vs 5.2 + /- 7.2 days ) and hospital stay ( 7.4 + /- 17.7 vs 14.4 + /- 12.8 days ) were significantly shorter in the endovascular cohort . At 1 and 2 years ' follow-up , the incidence of endoleaks was 6 % and 9 % , respectively . Through 2 years of follow-up , there were 3 re interventions in the endograft cohort and none in the open surgical control cohort . Kaplan-Meier analysis revealed no difference in overall mortality at 2 years . CONCLUSIONS In this multicenter study early outcomes with descending aortic endovascular stent grafting were very encouraging when compared with those of a well-matched surgical cohort . However , at 2 years ' follow-up , there is an incidence of endoleaks and re interventions associated with endovascular versus open surgical repair . Continued vigilant surveillance of patients treated with an endograft is important BACKGROUND Endovascular stent graft ( EV ) technology has been successfully adapted to the repair of blunt traumatic aortic injuries . The purpose of this study was to compare the outcomes of patients treated with EV repair and open repair after blunt thoracic aortic trauma . METHODS A review of a tertiary trauma center 's prospect i ve trauma registry identified all patients who suffered a blunt traumatic thoracic aortic injury over an 11-year period ( 1991 - 2002 ) . Operative interventions and outcomes were then compared . RESULTS Over an 11-year period , 18 patients underwent repair of a blunt thoracic aortic injury ( EV , 6 ; open , 12 ) . There were no significant differences in demographics , injury , or crash statistics between groups . The open group had a 17 % early mortality rate ( n = 2 ) , a paraplegia rate of 16 % ( n = 2 ) , and an 8.3 % incidence of recurrent laryngeal nerve injury ( n = 1 ) . This is in contrast to a 0 % rate of mortality , paraplegia , and recurrent laryngeal nerve injury in the EV group . A definite trend toward decreased morbidity , mortality , intensive care unit length of stay , and number of ventilator-dependent days was seen with EV repair . CONCLUSION We observed a clear trend toward improved outcomes after EV repair of thoracic aortic injuries compared with st and ard open repair . EV repair is emerging as the preferred method of repairing blunt thoracic aortic injuries in trauma patients with multiple injuries PURPOSE This report describes the authors ' initial experience with the Excluder thoracic endoprosthesis ( W. L. Gore and Associates , Inc , Flagstaff , Ariz ) and the thoracic Talent endoprosthesis ( Medtronic AVE , Sunrise , Fla ) and their safety and efficacy in the primary endovascular repair of descending thoracic aortic aneurysms ( TAAs ) . In addition , comparison with a historic nonr and omized cohort of patients that had undergone open repair of descending TAAs is reported . PATIENTS AND METHODS Repair of TAA ( mean diameter , 68 + /- 22 mm ) was attempted in 19 patients with the Excluder ( n = 14 ) and the Talent ( n = 5 ) endoprostheses between March 1999 and January 2000 . This group was compared with a historic nonr and omized cohort of 10 patients that had undergone open repair of anatomically similar descending TAA ( mean diameter , 74 + /- 22 mm ) between January 1996 and January 1998 . The mean age in the endovascular group was 70.6 + /- 5.3 years versus 70.1 + /- 4.5 years in the historic open group . All the procedures were performed in a st and ard operating room with angiographic capabilities . In the historic open group , each st and ard tube graft repair of descending TAA was performed by one of three staff surgeons . RESULTS Endograft deployment was successful in 18 patients ( 95 % ) . The procedure was aborted in one patient ( Excluder ) because of small iliac arteries and access difficulty . The average operative time was 155 + /- 62 minutes , with a mean blood loss of 325 + /- 353 mL ( versus 256 + /- 102 minutes and 1205 + /- 1493 mL , respectively , in the open group ) . Eight patients needed the planned use of more than one component for enhanced sealing or additional length in the endovascular group . No type I endoleaks were identified on the intraoperative completion angiography . One perioperative mortality occurred in the endovascular group and the open group . In the endovascular group , other complications included retroperitoneal hematoma and external iliac artery dissection ( n = 1 ) , lymphocele ( n = 1 ) , and common femoral artery pseudoaneurysm ( n = 1 ) . In the open group , other complications included ischemic colitis ( n = 1 ) , severe renal insufficiency ( n = 2 ) , wound infection ( n = 1 ) , and stroke ( n = 1 ) . In the endovascular group , the length of stay was 6.2 + /- 3.3 days ( range , 1 to 13 days ) , with only nine patients needing intensive care , whereas in the open group , the length of stay was 16.3 + /- 6.7 days , with all patients needing intensive care . Endoleaks , graft migrations , or ruptures were not seen on the 1-month , 6-month , and 12-month follow-up computed tomographic scans in the endovascular group . On the average , aneurysm size decreased from 68 + /- 22 mm to 58 + /- 13 mm , to 51 + /- 14 mm , and to 49 + /- 12 mm at 1 , 6 , and 12 months after endovascular repair , respectively . No spinal cord ischemia was seen in either group . CONCLUSION The endoluminal repair was effective in exclusion of descending TAAs from the systemic circulation in this selected group of patients . In this short-term follow-up , compared with the nonr and omized historic cohort of open descending TAA repair , the endovascular group had significantly shorter operating times and hospital and intensive care unit stays and lower operative blood loss . Further follow-up and continued assessment of the long-term durability of these devices in elective and emergency circumstances are warranted The magnitude of injury necessary to cause a traumatic aortic tear often results in high mortality . Open surgery in these patients is often not well tolerated . The purpose of this study was to compare the outcomes of three different treatment options in patients with traumatic aortic injuries . This was a retrospective review of a prospect ively maintained computer data base . Over a period of 33 months , 27 patients were diagnosed with thoracic aortic tears on the basis of a computed tomogram or a diagnostic angiogram . All patients were initially seen by trauma surgery staff and managed nonoperatively ( n = 12 ) if the predicted mortality due to associated injuries approached 100 % . Thoracic surgery staff were consulted on all other patients , and open surgical repair was performed in 10 patients . Thoracic stent grafts were used in five patients because of inability to ventilate following an attempted thoracotomy ( n = 2 ) or associated organ injury that prohibited anticoagulation ( head ± liver injury , n = 3 ) . Overall , patients in the endovascular group had a higher injury severity score than that of the open surgical group ( 42 ± 9 vs. 32 ± 11 ) . However , mortality was lowest in the endovascular group ( 20 % ) , higher in the open surgical group ( 50 % ) , and highest in the nonoperative group ( 92 % ) . No paraplegia was noted , and all surviving patients have been free of complications during the follow-up period . Due to the small number of patients in each treatment , no strong recommendations can be made . However , the results of thoracic stent grafts for patients with traumatic thoracic pseudoaneurysms may prove to be a safer and less invasive treatment option BACKGROUND Even with rapid diagnosis and effective medical treatment mortality in type B aortic dissection with evidence of extraaortic leakage of blood remains high . Considering a mortality rate of 29 % to 50 % associated with emergency surgical repair , the concept of endovascular stent-graft placement may become a life-saving option in impending or evolving rupture by endovascular sealing of the entry tear and subsequent abortion of leakage . METHODS The concept was tested by comparing short-term and 1-year outcomes of 11 patients after emergency endovascular stent-graft placement with historic-matched control patients subjected to conventional therapy . All patients had acute type B dissection complicated by loss of blood into periaortic spaces . RESULTS Emergency stent-graft placement was successful without periprocedural morbidity , aborted leakage , and ensured reconstruction of the dissected aorta ; at a mean follow-up of 15 + /- 6 months no death had occurred in the stent-graft group whereas four patients had died with conventional treatment ( p < 0.05 ) . CONCLUSION With appropriate logistics and expertise , type B aortic dissection with leakage and evolving rupture may benefit from nonsurgical reconstruction of the dissected segment by endovascular stent grafts BACKGROUND The treatment of thoracic aortic dissection is guided by prognostic and anatomical information . Proximal dissection requires surgery , but the appropriate treatment of distal thoracic aortic dissection has not been determined , because surgery has failed to improve the prognosis . METHODS We prospect ively evaluated the safety and efficacy of elective transluminal endovascular stent-graft insertion in 12 consecutive patients with descending ( type B ) aortic dissection and compared the results with surgery in 12 matched controls . In all 24 patients , aortic dissection was diagnosed by magnetic resonance angiography . In each group , the dissection involved the aortic arch in 3 patients and the descending thoracic aorta in all 12 patients . With the patient under general anesthesia , either surgical resection was undertaken or a custom- design ed endovascular stent-graft was placed by unilateral arteriotomy . RESULTS Stent-graft placement result ed in no morbidity or mortality , whereas surgery for type B dissection was associated with four deaths ( 33 percent , P=0.09 ) and five serious adverse events ( 42 percent , P=0.04 ) within 12 months . Transluminal placement of the stent-graft prosthesis was successful in all patients , with no leakage ; full expansion of the stents was ensured by balloon inflation at 2 to 3 atm . Sealing of the entry tear was monitored during the procedure by transesophageal ultrasonography and angiography , and thrombosis of the false lumen was confirmed in all 12 patients after a mean of three months by magnetic resonance imaging . There were no deaths or instances of paraplegia , stroke , embolization , side-branch occlusion , or infection in the stent-graft group ; nine patients had postimplantation syndrome , with transient elevation of C-reactive protein levels and body temperature plus mild leukocytosis . All the patients who received stent-grafts recovered , as did seven patients who underwent surgery for type B dissection ( 58 percent ) ( P=0.04 ) . CONCLUSIONS These preliminary observations suggest that elective , nonsurgical insertion of an endovascular stent-graft is safe and efficacious in selected patients who have thoracic aortic dissection and for whom surgery is indicated . Endoluminal repair may be useful for interventional reconstruction of thoracic aortic dissection Between 43,000 and 47,000 people die annually in the United States from diseases of the aorta and its branches and continues to increase . For the thoracic aorta , these diseases are increasingly treated by stent-grafting . No prospect i ve r and omized study exists comparing stent-grafting and open surgical treatment , including for disease subgroups . Currently , one stent-graft device is approved by the Food and Drug Administration for descending thoracic aortic aneurysms although two new devices are expected to obtain FDA approval in 2008 . Stent-graft devices are used " off label " or under physician Investigational Device Exemption studies for other indications such as traumatic rupture of the aorta and aortic dissection . Early first-generation devices suffered from problems such as stroke with insertion , ascending aortic dissection or aortic penetration from struts , vascular injury , graft collapse , endovascular leaks , graft material failure , continued aneurysm expansion or rupture , and migration or kinking ; however , the newer iterations coming to market have been considerably improved . Although the devices have been tested in pulse duplicators out to 10 years , long-term durability is not known , particularly in young patients . The long-term consequences of repeated computed tomography scans for checking device integrity and positioning on the risk of irradiation-induced cancer remains of concern in young patients . This document ( 1 ) review s the natural history of aortic disease , indications for repair , outcomes after conventional open surgery , currently available devices , and insights from outcomes of r and omized studies using stent-grafts for abdominal aortic aneurysm surgery , the latter having been treated for a longer time by stent-grafts ; and ( 2 ) offers suggestions for treatment OBJECTIVE Pivotal and comparative trial data are emerging for stent graft ( SG ) vs open repair of the thoracic aorta . We review ed procedure-related perioperative morbidity , mortality , and mid-term outcomes in a contemporary series of patients treated with SG of the thoracic aorta . The data were compared with those of a patient cohort concurrently treated with open surgical repair confined to the descending aorta . METHODS A review of patients undergoing SG procedures and open surgery of the thoracic aorta from January 1 , 1996 , to November 30 , 2005 , was performed from a prospect ively compiled data base . Study end points included perioperative complications , late survival , freedom from re interventions , and graft-related complications . Multivariate methods were used to assess variables potentially associated with study end points ; late outcomes were compared with actuarial methods . RESULTS In 105 patients ( mean age , 70 years ; 66 male [ 62.9 % ] ) SG repairs were done for 68 degenerative aneurysms ( 64.7 % ) , 12 penetrating ulcers ( 11.4 % ) , 15 pseudoaneurysms ( 14.3 % ) , 9 traumatic tears ( 8.6 % ) , and 1 acute dissection ( 0.9 % ) . Mean follow-up was 22 months ( range , 0 to 101 months ) . Eighty-nine ( 84.8 % ) SG patients were asymptomatic at presentation and underwent elective repair , whereas 16 ( 15.2 % ) presented with acute conditions and underwent urgent repair . Perioperative mortality was 7.6 % ( 8/105 ) , and actuarial survival at 48 months was 54 % + /- 7 % . The perioperative mortality rate among SG patients treated for degenerative pathology was 10.4 % ( 8/77 ) . Seven ( 6.7 % ) of 105 patients experienced spinal cord ischemic complications , including 2 patients with transient paraparesis that resolved by the time of discharge . Re interventions were performed in 10.5 % of patients ( 11/105 ) , with freedom from reintervention approaching 81 % by 48 months . Over the same interval , 93 patients were treated with open-surgical repair for descending thoracic aneurysm ( anastomosis cephalad to the celiac axis ) . Perioperative mortality in the open cohort was 15.1 % ( 14/93 ; P = .09 vs SG repair ) , and the 48-month actuarial survival was 64 % + /- 6 % . The incidence of spinal cord ischemic complications was 8.6 % ( 8/93 ) , including 4 patients with transient paraparesis ( P = .44 vs SG repair ) . Nine patients ( 9.7 % ) required surgical reintervention during the follow-up period , with 48-month freedom from reintervention approaching 79 % ( P = .73 vs SG repair ) . CONCLUSIONS Operative mortality was halved with SG , with similar late survival for both cohorts . Re interventions were required at a nearly identical rate for open repair and SG , and both groups experienced similar rates of spinal cord ischemic complications BACKGROUND Thoracic aortic endovascular repair ( TEVAR ) holds great promise in the elderly population . We conducted a concurrent comparison of TEVAR with open descending thoracic aneurysm repair ( DTAR ) in elderly patients to determine the more appropriate therapeutic option . METHODS Since 1993 , 93 patients aged 75 years and older have undergone open ( n = 41 ) or endovascular ( n = 52 ) descending aortic repair . Intervention indications included aneurysms , dissection , or traumatic injury . Mean maximum aortic diameter was 6.1 cm . Contained rupture was more frequent in TEVAR ( p = 0.005 ) ; 52 needed arch repair , and 46 needed total descending repair . RESULTS The mean age was 78.9 years ( TEVAR , 80.6 vs DTAR , 76.9 ; p < 0.0001 ) . The TEVAR patients had more significant comorbidities ; 42 ( 80.8 % ) were prospect ively identified as nonoperative c and i date s. Thirty-day mortality was higher in DTAR at 7 ( 17.1 % ) vs TEVAR at 3 ( 5.7 % , p = 0.1 ) . The composite end point of 30-day death , stroke , permanent paralysis , or dialysis requirement was similar ( TEVAR , 9 ; DTAR , 10 ; p = 0.45 ) . Median postoperative length of stay was shorter in TEVAR ( 6 days ) vs DTAR ( 13 days ; p = 0.003 ) . Endoleaks were observed in 12 . Actuarial survival at 48 months was similar ( mean survival : TEVAR , 30.2 months vs DTAR , 33.7 months ; p = 0.49 ) . CONCLUSIONS Despite more complex preoperative comorbidities , the TEVAR group had shorter hospitalization , a trend towards a reduction in early mortality , and similar late outcomes . This comparative analysis suggests that thoracic endovascular repair may be a more suitable therapeutic option in this complex elderly group |
12,847 | 24,007,323 | Results Apixaban , rivaroxaban and dabigatran have been found to be either non-inferior or superior to enoxaparin in prophylaxis of venous thromboembolism in knee and hip replacement with similar bleeding risk , superior to warfarin for stroke prevention in atrial fibrillation with significant reduction in the risk of major bleeding , non-inferior to aspirin for reducing cardiovascular death and stroke in acute coronary syndrome with significant increase in the risk of major bleed .
Rivaroxaban and dabigatran are also superior to the conventional agents in the management of symptomatic venous thromboembolism .
However , compared to enoxaparin , apixaban and rivaroxaban use lead to significantly increased bleeding risk in medically ill patients .
Conclusion Considering their pharmacological properties , their efficacy and bleeding complications , the new oral agents offer a net favourable clinical profile in orthopedic surgery , atrial fibrillation , acute coronary syndrome and increase the risk of bleeding in critically ill patients . | Background Anticoagulation with vitamin K antagonists such as warfarin has historically been used for the long term management of patients with thromboembolic disease .
However , these agents have a slow onset of action which requires bridging therapy with heparin and its analogues , which are available only in parenteral route .
To overcome these limitations , new oral anticoagulants such as factor Xa inhibitors and direct thrombin inhibitors have been developed .
The aim of this article is to systematic ally review the phase 3 clinical trials of new oral anticoagulants in common medical conditions . | BACKGROUND Apixaban , an oral potent reversible direct inhibitor of activated factor X , has shown promise in the prevention of venous thromboembolism following major orthopedic surgery . We conducted a dose-ranging study in patients with deep vein thrombosis . METHODS Consecutive patients with symptomatic deep vein thrombosis were included and r and omized to receive 84 - 91 days of apixaban 5 mg twice-daily , 10 mg twice-daily , or 20 mg once-daily , or low molecular weight heparin ( LMWH ) followed by a vitamin K antagonist ( VKA ) . The primary efficacy outcome was the composite of symptomatic recurrent venous thromboembolism and asymptomatic deterioration of bilateral compression ultrasound or perfusion lung scan . The principal safety outcome was the composite of major and clinical ly relevant , non-major bleeding . RESULTS The mean age of the 520 included patients was 59 years , and 62 % were male . The primary outcome occurred in 17 of the 358 apixaban-treated patients [ 4.7 % , 95 % confidence interval ( CI ) 2.8 - 7.5 % ] and in five of the 118 LMWH/VKA-treated patients ( 4.2 % , 95 % CI 1.4 - 9.6 % ) who were evaluable . The incidence in all three apixaban groups was low and comparable without evidence of a dose response . The principal safety outcome occurred in 28 ( 7.3 % ) of the 385 apixaban-treated patients and in 10 ( 7.9 % ) of the 126 LMWH/VKA-treated patients . No dose response for apixaban was observed . CONCLUSION These observations warrant further evaluation of apixaban in phase III studies . The attractive fixed-dose regimen of this compound may meet the dem and to simplify anticoagulant treatment in patients with established venous thromboembolism There is a clinical need for new oral anticoagulants to prevent and treat thromboembolic diseases . Given its integral role in the coagulation cascade , factor Xa is a particularly promising target for new anticoagulation therapies . The aim of this study was to investigate the safety , pharmacodynamics , and pharmacokinetics of BAY 59–7939 , an oral , direct factor Xa inhibitor The primary objective of this study was to compare the safety of four fixed-dose regimens of edoxaban with warfarin in patients with non-valvular atrial fibrillation ( AF ) . In this 12-week , parallel-group , multicentre , multinational study , 1,146 patients with AF and risk of stroke were r and omised to edoxaban 30 mg qd , 30 mg bid , 60 mg qd , or 60 mg bid or warfarin dose-adjusted to a target international normalised ratio of 2.0 - 3.0 . The study was double-blind to edoxaban dose , but open-label to warfarin . Primary outcomes were occurrence of major and /or clinical ly relevant non-major bleeding and elevated hepatic enzymes and /or bilirubin . Mean age was 65 + /- 8.7 years and 64.4 % were warfarin-naïve . Whereas major plus clinical ly relevant non-major bleeding occurred in 3.2 % of patients r and omised to warfarin , the incidence of bleeding was significantly higher with the edoxaban 60 mg bid ( 10.6 % ; p=0.002 ) and 30 mg bid regimens ( 7.8 % ; p=0.029 ) , but not with the edoxaban 60 mg qd ( 3.8 % ) or 30 mg qd regimens ( 3.0 % ) . For the same total daily dose of 60 mg , both bleeding frequency and trough edoxaban concentrations were higher in the 30-mg bid group than in the 60-mg qd group . There were no significant differences in hepatic enzyme elevations or bilirubin values among the groups . The safety profiles of edoxaban 30 and 60 mg qd in patients with AF were similar to warfarin . In contrast , the edoxaban bid regimens were associated with more bleeding than warfarin . These results suggest that in this three-month study , edoxaban 30 or 60 mg qd are safe and well-tolerated Edoxaban is an oral , reversible , direct factor Xa inhibitor in phase III clinical development for the prevention of stroke in atrial fibrillation ( AF ) . A phase II study was undertaken to evaluate the safety and efficacy of edoxaban in Asian patients with non-valvular AF with CHADS2 score ≥1 . In a multicentre , active-controlled , double-blind edoxaban and open-label warfarin , parallel-group study , a total of 235 patients from four Asian countries were r and omly assigned to edoxaban 30 mg qd , 60 mg qd or warfarin dose adjusted to international normalised ratio of 2 - 3 for three months . The primary endpoint was the incidence of central ly adjudicated all bleeding events ( major , clinical ly relevant non-major and minor ) . Secondary endpoints included thromboembolic events , biomarkers of thrombus formation and all adverse events ( AEs ) . The incidence of all bleeding events ( 95 % CI ) was 20.3 % ( 12.9 , 30.4 ) for edoxaban 30 mg , 23.8 % ( 15.8 , 34.1 ) for edoxaban 60 mg , and 29.3 % ( 20.2 , 40.4 ) for warfarin . A subgroup analysis suggested low body weight ( ≤60 kg ) may affect the incidence of bleeding events with edoxaban . The incidence of study drug-related AEs was 22 % for edoxaban 30 mg , 29 % for edoxaban 60 mg and 33 % for warfarin . No thromboembolic events occurred in any treatment group . In conclusion , this phase II study found a trend for a reduction in the incidence of all bleeding events in Asian AF patients with edoxaban 30 mg and 60 mg compared with warfarin . Adverse events were similar between the edoxaban 60-mg and warfarin groups and were lower with the edoxaban 30-mg group BACKGROUND Warfarin reduces the risk of stroke in patients with atrial fibrillation but increases the risk of hemorrhage and is difficult to use . Dabigatran is a new oral direct thrombin inhibitor . METHODS In this noninferiority trial , we r and omly assigned 18,113 patients who had atrial fibrillation and a risk of stroke to receive , in a blinded fashion , fixed doses of dabigatran--110 mg or 150 mg twice daily -- or , in an unblinded fashion , adjusted-dose warfarin . The median duration of the follow-up period was 2.0 years . The primary outcome was stroke or systemic embolism . RESULTS Rates of the primary outcome were 1.69 % per year in the warfarin group , as compared with 1.53 % per year in the group that received 110 mg of dabigatran ( relative risk with dabigatran , 0.91 ; 95 % confidence interval [ CI ] , 0.74 to 1.11 ; P<0.001 for noninferiority ) and 1.11 % per year in the group that received 150 mg of dabigatran ( relative risk , 0.66 ; 95 % CI , 0.53 to 0.82 ; P<0.001 for superiority ) . The rate of major bleeding was 3.36 % per year in the warfarin group , as compared with 2.71 % per year in the group receiving 110 mg of dabigatran ( P=0.003 ) and 3.11 % per year in the group receiving 150 mg of dabigatran ( P=0.31 ) . The rate of hemorrhagic stroke was 0.38 % per year in the warfarin group , as compared with 0.12 % per year with 110 mg of dabigatran ( P<0.001 ) and 0.10 % per year with 150 mg of dabigatran ( P<0.001 ) . The mortality rate was 4.13 % per year in the warfarin group , as compared with 3.75 % per year with 110 mg of dabigatran ( P=0.13 ) and 3.64 % per year with 150 mg of dabigatran ( P=0.051 ) . CONCLUSIONS In patients with atrial fibrillation , dabigatran given at a dose of 110 mg was associated with rates of stroke and systemic embolism that were similar to those associated with warfarin , as well as lower rates of major hemorrhage . Dabigatran administered at a dose of 150 mg , as compared with warfarin , was associated with lower rates of stroke and systemic embolism but similar rates of major hemorrhage . ( Clinical Trials.gov number , NCT00262600 . BACKGROUND Heparins and warfarin are currently used as venous thromboembolism ( VTE ) prophylaxis in surgery . Inhibition of factor ( F ) Xa provides a specific mechanism of anticoagulation and the potential for an improved benefit-risk profile . OBJECTIVES To evaluate the safety and efficacy of apixaban , a potent , direct , oral inhibitor of FXa , in patients following total knee replacement ( TKR ) , and to investigate dose-response relationships . PATIENTS / METHODS A total of 1238 patients were r and omized to one of six double-blind apixaban doses [ 5 , 10 or 20 mg day(-1 ) administered as a single ( q.d . ) or a twice-daily divided dose ( b.i.d . ) ] , enoxaparin ( 30 mg b.i.d . ) or open-label warfarin ( titrated to an International Normalized Ratio of 1.8 - 3.0 ) . Treatment lasted 10 - 14 days , commencing 12 - 24 h after surgery with apixaban or enoxaparin , and on the evening of surgery with warfarin . The primary efficacy outcome was a composite of VTE ( m and atory venography ) and all-cause mortality during treatment . The primary safety outcome was major bleeding . RESULTS A total of 1217 patients were eligible for safety and 856 patients for efficacy analysis . All apixaban groups had lower primary efficacy event rates than either comparator . The primary outcome rate decreased with increasing apixaban dose ( P = 0.09 with q.d./b.i.d . regimens combined , P = 0.19 for q.d . and P = 0.13 for b.i.d . dosing).A significant dose-related increase in the incidence of total adjudicated bleeding events was noted in the q.d . ( P = 0.01 ) and b.i.d . ( P = 0.02 ) apixaban groups ; there was no difference between q.d . and b.i.d . regimens . CONCLUSIONS Apixaban in doses of 2.5 mg b.i.d . or 5 mg q.d . has a promising benefit-risk profile compared with the current st and ards of care following TKR OBJECTIVE The aim of this study was to investigate the pharmacokinetics and pharmacodynamics of rivaroxaban -- a novel , oral , direct Factor Xa ( FXa ) inhibitor -- in healthy elderly subjects . RESEARCH DESIGN AND METHODS In this single-centre , single-blind , placebo-controlled , parallel-group , dose-escalation study , 48 subjects ( aged 60 - 76 years ) were r and omized to receive a single oral dose of 30 , 40 or 50 mg of rivaroxaban or placebo . RESULTS Rivaroxaban was absorbed rapidly , reaching peak plasma concentration ( C(max ) ) 4 h after dosing in all groups . Bioavailability , in terms of the area under the plasma concentration-time curve ( AUC ) and C(max ) , increased slightly ( less than dose proportionally ) after administration of rivaroxaban 40 mg compared with 30 mg , but was not increased further with rivaroxaban 50 mg . Rivaroxaban pharmacodynamic effects ( inhibition of FXa activity and prolongation of prothrombin time , activated partial thromboplastin time and HepTest ) all showed a similar pattern , with maximum inhibition of FXa activity increasing from 68 % after rivaroxaban 30 mg to 75 % after 40 mg and no further increase with the 50 mg dose . Most adverse events were mild ; observed rates were less than placebo for the 30 and 40 mg dose groups , and similar to placebo for 50 mg . No differences were found between male and female subjects . Effects of rivaroxaban doses above 50 mg were not investigated in this study . CONCLUSIONS Each single dose of rivaroxaban was well tolerated , with predictable pharmacokinetics and pharmacodynamics at doses up to 40 mg , and provided effective anticoagulation in healthy elderly subjects . Adverse events were somewhat elevated in the 50 mg group , but given the small sample size , no specific conclusions can be drawn about this dosing level BACKGROUND The direct oral thrombin inhibitor dabigatran has a predictable anticoagulant effect and may be an alternative therapy to warfarin for patients who have acute venous thromboembolism . METHODS In a r and omized , double-blind , noninferiority trial involving patients with acute venous thromboembolism who were initially given parenteral anticoagulation therapy for a median of 9 days ( interquartile range , 8 to 11 ) , we compared oral dabigatran , administered at a dose of 150 mg twice daily , with warfarin that was dose-adjusted to achieve an international normalized ratio of 2.0 to 3.0 . The primary outcome was the 6-month incidence of recurrent symptomatic , objective ly confirmed venous thromboembolism and related deaths . Safety end points included bleeding events , acute coronary syndromes , other adverse events , and results of liver-function tests . RESULTS A total of 30 of the 1274 patients r and omly assigned to receive dabigatran ( 2.4 % ) , as compared with 27 of the 1265 patients r and omly assigned to warfarin ( 2.1 % ) , had recurrent venous thromboembolism ; the difference in risk was 0.4 percentage points ( 95 % confidence interval [ CI ] , -0.8 to 1.5 ; P<0.001 for the prespecified noninferiority margin ) . The hazard ratio with dabigatran was 1.10 ( 95 % CI , 0.65 to 1.84 ) . Major bleeding episodes occurred in 20 patients assigned to dabigatran ( 1.6 % ) and in 24 patients assigned to warfarin ( 1.9 % ) ( hazard ratio with dabigatran , 0.82 ; 95 % CI , 0.45 to 1.48 ) , and episodes of any bleeding were observed in 205 patients assigned to dabigatran ( 16.1 % ) and 277 patients assigned to warfarin ( 21.9 % ; hazard ratio with dabigatran , 0.71 ; 95 % CI , 0.59 to 0.85 ) . The numbers of deaths , acute coronary syndromes , and abnormal liver-function tests were similar in the two groups . Adverse events leading to discontinuation of the study drug occurred in 9.0 % of patients assigned to dabigatran and in 6.8 % of patients assigned to warfarin ( P=0.05 ) . CONCLUSIONS For the treatment of acute venous thromboembolism , a fixed dose of dabigatran is as effective as warfarin , has a safety profile that is similar to that of warfarin , and does not require laboratory monitoring . ( Clinical Trials.gov number , NCT00291330 . AIMS Patients with non-valvular atrial fibrillation ( AF ) and renal insufficiency are at increased risk for ischaemic stroke and bleeding during anticoagulation . Rivaroxaban , an oral , direct factor Xa inhibitor metabolized predominantly by the liver , preserves the benefit of warfarin for stroke prevention while causing fewer intracranial and fatal haemorrhages . METHODS AND RESULTS We r and omized 14 264 patients with AF in a double-blind trial to rivaroxaban 20 mg/day [ 15 mg/day if creatinine clearance ( CrCl ) 30 - 49 mL/min ] or dose-adjusted warfarin ( target international normalized ratio 2.0 - 3.0 ) . Compared with patients with CrCl > 50 mL/min ( mean age 73 years ) , the 2950 ( 20.7 % ) patients with CrCl 30 - 49 mL/min were older ( 79 years ) and had higher event rates irrespective of study treatment . Among those with CrCl 30 - 49 mL/min , the primary endpoint of stroke or systemic embolism occurred in 2.32 per 100 patient-years with rivaroxaban 15 mg/day vs. 2.77 per 100 patient-years with warfarin [ hazard ratio ( HR ) 0.84 ; 95 % confidence interval ( CI ) 0.57 - 1.23 ] in the per- protocol population . Intention-to-treat analysis yielded similar results ( HR 0.86 ; 95 % CI 0.63 - 1.17 ) to the per- protocol results . Rates of the principal safety endpoint ( major and clinical ly relevant non-major bleeding : 17.82 vs. 18.28 per 100 patient-years ; P = 0.76 ) and intracranial bleeding ( 0.71 vs. 0.88 per 100 patient-years ; P = 0.54 ) were similar with rivaroxaban or warfarin . Fatal bleeding ( 0.28 vs. 0.74 % per 100 patient-years ; P = 0.047 ) occurred less often with rivaroxaban . CONCLUSION Patients with AF and moderate renal insufficiency have higher rates of stroke and bleeding than those with normal renal function . There was no evidence of heterogeneity in treatment effect across dosing groups . Dose adjustment in ROCKET-AF yielded results consistent with the overall trial in comparison with dose-adjusted warfarin Background — An effective and safe oral anticoagulant that needs no monitoring for dose adjustment is urgently needed for the treatment of diseases that require long-term anticoagulation . Rivaroxaban ( BAY 59 - 7939 ) is an oral direct factor Xa inhibitor currently under clinical development . Methods and Results — This r and omized , parallel-group phase II trial in patients with proximal deep-vein thrombosis explored the efficacy and safety of rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily compared with enoxaparin 1 mg/kg BID followed by vitamin K antagonist . Each treatment was administered for 12 weeks . The primary efficacy end point was an improvement in thrombotic burden at day 21 ( assessed by quantitative compression ultrasonography ; ≥4-point improvement in thrombus score ) without recurrent symptomatic venous thromboembolism or venous thromboembolism – related death . The primary safety end point was major bleeding during 12 weeks of treatment . Outcomes were adjudicated central ly without knowledge of treatment allocation . The primary efficacy end point was achieved in 53 ( 53.0 % ) of 100 , 58 ( 59.2 % ) of 98 , 62 ( 56.9 % ) of 109 , and 49 ( 43.8 % ) of 112 patients receiving rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily , respectively , compared with 50 ( 45.9 % ) of 109 patients treated with enoxaparin/vitamin K antagonist . There was no significant trend in the dose – response relationship between rivaroxaban BID and the primary efficacy end point ( P=0.67 ) . Major bleeding was observed in 1.7 % , 1.7 % , 3.3 % , and 1.7 % of patients receiving rivaroxaban 10 , 20 , or 30 mg BID or 40 mg once daily , respectively . There were no major bleeding events with enoxaparin/vitamin K antagonist . Conclusions — Results of this proof-of-concept and dose-finding study support phase III evaluation of the orally active direct factor Xa inhibitor rivaroxaban , because efficacy and safety were apparent in the treatment of proximal deep-vein thrombosis across a 3-fold range of fixed daily dosing BACKGROUND Acute coronary syndromes arise from coronary atherosclerosis with superimposed thrombosis . Since factor Xa plays a central role in thrombosis , the inhibition of factor Xa with low-dose rivaroxaban might improve cardiovascular outcomes in patients with a recent acute coronary syndrome . METHODS In this double-blind , placebo-controlled trial , we r and omly assigned 15,526 patients with a recent acute coronary syndrome to receive twice-daily doses of either 2.5 mg or 5 mg of rivaroxaban or placebo for a mean of 13 months and up to 31 months . The primary efficacy end point was a composite of death from cardiovascular causes , myocardial infa rct ion , or stroke . RESULTS Rivaroxaban significantly reduced the primary efficacy end point , as compared with placebo , with respective rates of 8.9 % and 10.7 % ( hazard ratio in the rivaroxaban group , 0.84 ; 95 % confidence interval [ CI ] , 0.74 to 0.96 ; P=0.008 ) , with significant improvement for both the twice-daily 2.5-mg dose ( 9.1 % vs. 10.7 % , P=0.02 ) and the twice-daily 5-mg dose ( 8.8 % vs. 10.7 % , P=0.03 ) . The twice-daily 2.5-mg dose of rivaroxaban reduced the rates of death from cardiovascular causes ( 2.7 % vs. 4.1 % , P=0.002 ) and from any cause ( 2.9 % vs. 4.5 % , P=0.002 ) , a survival benefit that was not seen with the twice-daily 5-mg dose . As compared with placebo , rivaroxaban increased the rates of major bleeding not related to coronary-artery bypass grafting ( 2.1 % vs. 0.6 % , P<0.001 ) and intracranial hemorrhage ( 0.6 % vs. 0.2 % , P=0.009 ) , without a significant increase in fatal bleeding ( 0.3 % vs. 0.2 % , P=0.66 ) or other adverse events . The twice-daily 2.5-mg dose result ed in fewer fatal bleeding events than the twice-daily 5-mg dose ( 0.1 % vs. 0.4 % , P=0.04 ) . CONCLUSIONS In patients with a recent acute coronary syndrome , rivaroxaban reduced the risk of the composite end point of death from cardiovascular causes , myocardial infa rct ion , or stroke . Rivaroxaban increased the risk of major bleeding and intracranial hemorrhage but not the risk of fatal bleeding . ( Funded by Johnson & Johnson and Bayer Healthcare ; ATLAS ACS 2-TIMI 51 Clinical Trials.gov number , NCT00809965 . ) BACKGROUND After hip replacement surgery , prophylaxis following discharge from hospital is recommended to reduce the risk of venous thromboembolism . Our aim was to assess the oral , direct thrombin inhibitor dabigatran etexilate for such prophylaxis . METHODS In this double-blind study , we r and omised 3494 patients undergoing total hip replacement to treatment for 28 - 35 days with dabigatran etexilate 220 mg ( n=1157 ) or 150 mg ( 1174 ) once daily , starting with a half-dose 1 - 4 h after surgery , or subcutaneous enoxaparin 40 mg once daily ( 1162 ) , starting the evening before surgery . The primary efficacy outcome was the composite of total venous thromboembolism ( venographic or symptomatic ) and death from all causes during treatment . On the basis of the absolute difference in rates of venous thromboembolism with enoxaparin versus placebo , the non-inferiority margin for the difference in rates of thromboembolism was defined as 7.7 % . Efficacy analyses were done by modified intention to treat . This trial is registered with Clinical Trials.gov , number NCT00168818 . FINDINGS Median treatment duration was 33 days . 880 patients in the dabigatran etexilate 220 mg group , 874 in the dabigatran etexilate 150 mg group , and 897 in the enoxaparin group were available for the primary efficacy outcome analysis ; the main reasons for exclusion in all three groups were the lack of adequate venographic data . The primary efficacy outcome occurred in 60 ( 6.7 % ) of 897 individuals in the enoxaparin group versus 53 ( 6.0 % ) of 880 patients in the dabigatran etexilate 220 mg group ( absolute difference -0.7 % , 95 % CI -2.9 to 1.6 % ) and 75 ( 8.6 % ) of 874 people in the 150 mg group ( 1.9 % , -0.6 to 4.4 % ) . Both doses were thus non-inferior to enoxaparin . There was no significant difference in major bleeding rates with either dose of dabigatran etexilate compared with enoxaparin ( p=0.44 for 220 mg , p=0.60 for 150 mg ) . The frequency of increases in liver enzyme concentrations and of acute coronary events during the study did not differ significantly between the groups . INTERPRETATION Oral dabigatran etexilate was as effective as enoxaparin in reducing the risk of venous thromboembolism after total hip replacement surgery , with a similar safety profile The primary objective of this study was to assess the effect of a st and ard high-fat meal on the single-dose ( 60 mg ) pharmacokinetics ( PK ) of edoxaban in healthy Japanese and Caucasian male volunteers matched by body mass index . This was an open-label , r and omized , 2-period crossover study . All 32 enrolled volunteers completed the study per protocol . Both serial blood and urine sample s were collected , and edoxaban concentrations were analyzed by a vali date d liquid chromatography/t and em mass spectrometry method . Activated partial thromboplastin and prothrombin times were obtained as measures of pharmacodynamic effect . The point estimates of the geometric mean ratios ( fed/fasted ) for AUC(0-t ) , AUC(0-∞ ) , and C(max ) demonstrated modest increases ranging from 6 % to 22 % across PK parameters for both race cohorts . The disposition was similar in both Japanese and Caucasian matched volunteers with slightly higher AUC values ( ranging from 7%-9 % ) in Caucasians . There were no serious adverse events during the study . All drug-related adverse events were mild and self-limited , and none were bleeding related . Both Japanese and Caucasian volunteers demonstrated a modest but clinical ly insignificant food effect . It was concluded that edoxaban can be administered without regard to food BACKGROUND Dabigatran etexilate , a novel oral direct thrombin inhibitor , has been approved for prophylaxis of thromboembolism in patients undergoing total knee or total hip replacement , and is under clinical investigation for treatment of venous thromboembolism , prevention of stroke in patients with atrial fibrillation , and the treatment of thromboembolic complications following acute coronary syndromes . OBJECTIVE To evaluate the potential impact of atorvastatin coadministration on the pharmacokinetics , pharmacodynamics , and safety of dabigatran etexilate . METHODS Healthy male and female volunteers ( n = 22 ) were recruited to this open , r and omized , multiple-dose , three-way crossover study . They received dabigatran etexilate 150 mg twice daily on days 1 - 3 and once daily on day 4 , atorvastatin 80 mg once daily on days 1 - 4 , or both treatments together on days 1 - 4 . RESULTS Exposure to dabigatran at steady state ( area under the drug plasma concentration-time curve at steady state ) was reduced by 18 % with concomitant atorvastatin administration . An 18 % increase in plasma atorvastatin concentration occurred with coadministration of dabigatran etexilate . Exposure to its metabolite 2'-hydroxy-atorvastatin remained essentially unchanged and exposure to 4'-hydroxy-atorvastatin was increased by 15 % . The small changes observed are deemed of little clinical relevance given the overall inter-individual variability in the metabolism of atorvastatin . Furthermore , there were no changes in the concentrations of active HMG-CoA reductase inhibitors in plasma following dabigatran etexilate coadministration . Six subjects in the atorvastatin treatment group , six subjects during combination treatment , and eight subjects in the dabigatran treatment group reported adverse events . Most of the adverse events reported were nervous system disorders such as dizziness and headache , and general disorders such as fatigue . All adverse events were resolved at the end of the study . CONCLUSION Results of this r and omized , open-label , three-way crossover design study in healthy male and female volunteers showed that atorvastatin had no influence on the pharmacokinetic/pharmacodynamic profile of dabigatran , and vice versa , dabigatran etexilate had no impact on the pharmacokinetic/pharmacodynamic profile of atorvastatin . Both drugs were well tolerated when given alone or in combination BACKGROUND Rivaroxaban is an oral direct factor Xa inhibitor that has been effective in prevention of venous thromboembolism in patients undergoing elective orthopaedic surgery . However , its use after acute coronary syndromes has not been investigated . In this setting , we assessed the safety and efficacy of rivaroxaban and aim ed to select the most favourable dose and dosing regimen . METHODS In this double-blind , dose-escalation , phase II study , undertaken at 297 sites in 27 countries , 3491 patients stabilised after an acute coronary syndrome were stratified on the basis of investigator decision to use aspirin only ( stratum 1 , n=761 ) or aspirin plus a thienopyridine ( stratum 2 , n=2730 ) . Participants were r and omised within each strata and dose tier with a block r and omisation method at 1:1:1 to receive either placebo or rivaroxaban ( at doses 5 - 20 mg ) given once daily or the same total daily dose given twice daily . The primary safety endpoint was clinical ly significant bleeding ( TIMI major , TIMI minor , or requiring medical attention ) ; the primary efficacy endpoint was death , myocardial infa rct ion , stroke , or severe recurrent ischaemia requiring revascularisation during 6 months . Safety analyses included all participants who received at least one dose of study drug ; efficacy analyses were by intention to treat . This study is registered with Clinical Trials.gov , number NCT00402597 . FINDINGS Three patients in stratum 1 and 26 in stratum 2 never received the study drug . The risk of clinical ly significant bleeding with rivaroxaban versus placebo increased in a dose-dependent manner ( hazard ratios [ HRs ] 2.21 [ 95 % CI 1.25 - 3.91 ] for 5 mg , 3.35 [ 2.31 - 4.87 ] for 10 mg , 3.60 [ 2.32 - 5.58 ] for 15 mg , and 5.06 [ 3.45 - 7.42 ] for 20 mg doses ; p<0.0001 ) . Rates of the primary efficacy endpoint were 5.6 % ( 126/2331 ) for rivaroxaban versus 7.0 % ( 79/1160 ) for placebo ( HR 0.79 [ 0.60 - 1.05 ] , p=0.10 ) . Rivaroxaban reduced the main secondary efficacy endpoint of death , myocardial infa rct ion , or stroke compared with placebo ( 87/2331 [ 3.9 % ] vs 62/1160 [ 5.5 % ] ; HR 0.69 , [ 95 % CI 0.50 - 0.96 ] , p=0.0270 ) . The most common adverse event in both groups was chest pain ( 248/2309 [ 10.7 % ] vs 118/1153 [ 10.2 % ] ) . INTERPRETATION The use of an oral factor Xa inhibitor in patients stabilised after an acute coronary syndrome increases bleeding in a dose-dependent manner and might reduce major ischaemic outcomes . On the basis of these observations , a phase III study of low-dose rivaroxaban as adjunctive therapy in these patients is underway . FUNDING Johnson & Johnson Pharmaceutical Research & Development and Bayer Healthcare AG BACKGROUND Apixaban , an oral , direct factor Xa inhibitor , may reduce the risk of recurrent ischemic events when added to antiplatelet therapy after an acute coronary syndrome . METHODS We conducted a r and omized , double-blind , placebo-controlled clinical trial comparing apixaban , at a dose of 5 mg twice daily , with placebo , in addition to st and ard antiplatelet therapy , in patients with a recent acute coronary syndrome and at least two additional risk factors for recurrent ischemic events . RESULTS The trial was terminated prematurely after recruitment of 7392 patients because of an increase in major bleeding events with apixaban in the absence of a counterbalancing reduction in recurrent ischemic events . With a median follow-up of 241 days , the primary outcome of cardiovascular death , myocardial infa rct ion , or ischemic stroke occurred in 279 of the 3705 patients ( 7.5 % ) assigned to apixaban ( 13.2 events per 100 patient-years ) and in 293 of the 3687 patients ( 7.9 % ) assigned to placebo ( 14.0 events per 100 patient-years ) ( hazard ratio with apixaban , 0.95 ; 95 % confidence interval [ CI ] , 0.80 to 1.11 ; P=0.51 ) . The primary safety outcome of major bleeding according to the Thrombolysis in Myocardial Infa rct ion ( TIMI ) definition occurred in 46 of the 3673 patients ( 1.3 % ) who received at least one dose of apixaban ( 2.4 events per 100 patient-years ) and in 18 of the 3642 patients ( 0.5 % ) who received at least one dose of placebo ( 0.9 events per 100 patient-years ) ( hazard ratio with apixaban , 2.59 ; 95 % CI , 1.50 to 4.46 ; P=0.001 ) . A greater number of intracranial and fatal bleeding events occurred with apixaban than with placebo . CONCLUSIONS The addition of apixaban , at a dose of 5 mg twice daily , to antiplatelet therapy in high-risk patients after an acute coronary syndrome increased the number of major bleeding events without a significant reduction in recurrent ischemic events . ( Funded by Bristol-Myers Squibb and Pfizer ; APPRAISE-2 Clinical Trials.gov number , NCT00831441 . ) BACKGROUND The efficacy and safety of prolonging prophylaxis for venous thromboembolism in medically ill patients beyond hospital discharge remain uncertain . We hypothesized that extended prophylaxis with apixaban would be safe and more effective than short-term prophylaxis with enoxaparin . METHODS In this double-blind , double-dummy , placebo-controlled trial , we r and omly assigned acutely ill patients who had congestive heart failure or respiratory failure or other medical disorders and at least one additional risk factor for venous thromboembolism and who were hospitalized with an expected stay of at least 3 days to receive apixaban , administered orally at a dose of 2.5 mg twice daily for 30 days , or enoxaparin , administered subcutaneously at a dose of 40 mg once daily for 6 to 14 days . The primary efficacy outcome was the 30-day composite of death related to venous thromboembolism , pulmonary embolism , symptomatic deep-vein thrombosis , or asymptomatic proximal-leg deep-vein thrombosis , as detected with the use of systematic bilateral compression ultrasonography on day 30 . The primary safety outcome was bleeding . All efficacy and safety outcomes were independently adjudicated . RESULTS A total of 6528 subjects underwent r and omization , 4495 of whom could be evaluated for the primary efficacy outcome --2211 in the apixaban group and 2284 in the enoxaparin group . Among the patients who could be evaluated , 2.71 % in the apixaban group ( 60 patients ) and 3.06 % in the enoxaparin group ( 70 patients ) met the criteria for the primary efficacy outcome ( relative risk with apixaban , 0.87 ; 95 % confidence interval [ CI ] , 0.62 to 1.23 ; P=0.44 ) . By day 30 , major bleeding had occurred in 0.47 % of the patients in the apixaban group ( 15 of 3184 patients ) and in 0.19 % of the patients in the enoxaparin group ( 6 of 3217 patients ) ( relative risk , 2.58 ; 95 % CI , 1.02 to 7.24 ; P=0.04 ) . CONCLUSIONS In medically ill patients , an extended course of thromboprophylaxis with apixaban was not superior to a shorter course with enoxaparin . Apixaban was associated with significantly more major bleeding events than was enoxaparin . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00457002 . ) BACKGROUND Oral anticoagulants , such as dabigatran etexilate , an oral , direct thrombin inhibitor , that do not require monitoring or dose adjustment offer potential for prophylaxis against venous thromboembolism ( VTE ) after total knee replacement surgery . METHODS In this r and omized , double-blind study , 2076 patients undergoing total knee replacement received dabigatran etexilate , 150 mg or 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery , for 6 - 10 days . Patients were followed-up for 3 months . The primary efficacy outcome was a composite of total VTE ( venographic or symptomatic ) and mortality during treatment , and the primary safety outcome was the incidence of bleeding events . RESULTS The primary efficacy outcome occurred in 37.7 % ( 193 of 512 ) of the enoxaparin group versus 36.4 % ( 183 of 503 ) of the dabigatran etexilate 220 mg group ( absolute difference , -1.3 % ; 95 % CI , -7.3 to 4.6 ) and 40.5 % ( 213 of 526 ) of the 150 mg group ( 2.8 % ; 95 % CI , -3.1 to 8.7 ) . Both doses were noninferior to enoxaparin based on the pre-specified noninferiority criterion . The incidence of major bleeding did not differ significantly between the three groups ( 1.3 % versus 1.5 % and 1.3 % respectively ) . No significant differences in the incidences of liver enzyme elevation and acute coronary events were observed during treatment or follow-up . CONCLUSIONS Dabigatran etexilate ( 220 mg or 150 mg ) was at least as effective and with a similar safety profile as enoxaparin for prevention of VTE after total knee-replacement surgery Edoxaban is a new oral direct factor Xa inhibitor . The purpose of this study was to evaluate the efficacy and safety of different doses of edoxaban for the prevention of venous thromboembolism ( VTE ) in patients undergoing elective total hip replacement . A total of 903 patients were r and omised to oral edoxaban 15 , 30 , 60 or 90 mg once daily or subcutaneous dalteparin once daily ( initial dose 2,500 IU , subsequent doses 5,000 IU ) . Both drugs were begun 6 - 8 hours postoperatively and continued for 7 - 10 days , when bilateral venography was performed . The primary efficacy endpoint was the incidence of total VTE , which included proximal and /or distal deep-vein thrombosis ( DVT ) by venography or symptomatic , objective ly confirmed DVT or pulmonary embolism during the treatment period . The primary safety outcome was the incidence of the composite of major and clinical ly relevant non-major bleeding . All venograms and bleeding events were review ed by a central independent adjudication committee blinded as to treatment allocation . Of the 903 patients r and omised , 776 were evaluable for the primary efficacy analysis . The incidences of VTE were 28.2 % , 21.2 % , 15.2 % , and 10.6 % in patients receiving edoxaban 15 , 30 , 60 and 90 mg , respectively , compared with 43.8 % in the dalteparin group ( p<0.005 ) . There was a statistically significant ( p<0.001 ) dose-response for efficacy across the edoxaban dose groups for total VTE and for major VTE . The incidence of clinical ly relevant bleeding was low and similar across the groups . Oral edoxaban once daily is effective for preventing VTE after total hip replacement BACKGROUND Guidelines recommend warfarin as the st and ard of care for patients with atrial fibrillation ( AF ) at moderate or high risk for stroke . This phase II study assessed the effects of 2 doses of the factor Xa inhibitor apixaban vs. warfarin in Japanese patients with non-valvular AF . The composite primary endpoint was major and clinical ly relevant non-major ( CRNM ) bleeding . METHODS AND RESULTS Two hundred and twenty-two patients with AF and 1 or more additional risk factors for stroke were r and omized ( 1:1:1 ) to double-blind apixaban 2.5 or 5 mg b.i.d . or open-label warfarin ( target international normalized ratio 2.0 - 3.0 ; 2.0 - 2.6 if age ≥ 70 years ) for 12 weeks . The primary endpoint occurred in 1 patient ( 1.4 % ) in each apixaban group and 4 ( 5.3 % ) warfarin patients . There were no strokes , systemic emboli , myocardial infa rct ions , or deaths in either apixaban group . The warfarin group had 2 ischemic strokes and 1 subarachnoid hemorrhage , but there were no deaths . Major and CRNM bleeds each occurred with higher frequency in the warfarin group vs. either apixaban group . Most adverse events were mild or moderate . No patients had hepatic aminotransferase elevations greater than 3 times the upper limit of normal . CONCLUSIONS In Japanese patients with AF , apixaban 2.5 and 5 mg b.i.d . were well tolerated over 12 weeks . A global phase III trial , which includes Japanese patients , is ongoing ( Clinical Trials.gov Identifier NCT00787150 ) AIM After an acute coronary syndrome , patients remain at risk of recurrent ischaemic events , despite contemporary treatment , including aspirin and clopidogrel . We evaluated the safety and indicators of efficacy of the novel oral direct thrombin inhibitor dabigatran . METHODS AND RESULTS In this double-blind , placebo-controlled , dose-escalation trial , 1861 patients ( 99.2 % on dual antiplatelet treatment ) in 161 centres were enrolled at mean 7.5 days ( SD 3.8 ) after an ST-elevation ( 60 % ) or non-ST-elevation ( 40 % ) myocardial infa rct ion and r and omized to twice daily treatment with dabigatran 50 mg ( n = 369 ) , 75 mg ( n = 368 ) , 110 mg ( n = 406 ) , 150 mg ( n = 347 ) , or placebo ( n = 371 ) . Primary outcome was the composite of major or clinical ly relevant minor bleeding during the 6-month treatment period . There were 96 primary outcome events and , compared with placebo , a dose-dependent increase with dabigatran , hazard ratio ( HR ) 1.77 ( 95 % confidence intervals 0.70 , 4.50 ) for 50 mg ; HR 2.17 ( 0.88 , 5.31 ) for 75 mg ; HR 3.92 ( 1.72 , 8.95 ) for 110 mg ; and HR 4.27 ( 1.86 , 9.81 ) for 150 mg . Compared with placebo , D-dimer concentrations were reduced in all dabigatran dose groups by an average of 37 and 45 % at weeks 1 and 4 , respectively ( P < 0.001 ) . Fourteen ( 3.8 % ) patients died , had a myocardial infa rct ion or stroke in the placebo group compared with 17 ( 4.6 % ) in 50 mg , 18 ( 4.9 % ) in 75 mg , 12 ( 3.0 % ) in 110 mg , and 12 ( 3.5 % ) in the 150 mg dabigatran groups . CONCLUSIONS Dabigatran , in addition to dual antiplatelet therapy , was associated with a dose-dependent increase in bleeding events and significantly reduced coagulation activity in patients with a recent myocardial infa rct ion Dabigatran etexilate is an oral low-molecular-weight direct thrombin inhibitor . Following oral administration , dabigatran etexilate is rapidly converted to its active form , dabigatran . The authors investigated the absorption , distribution , and elimination of a single 150-mg dose capsule formulation of dabigatran etexilate in healthy volunteers and patients undergoing total hip replacement . In an open-label , 3-way crossover study , dabigatran etexilate was administered to 18 male volunteers in the fasted state , after administration of food and with coadministration of the proton pump inhibitor , pantoprazole . In a subsequent multicenter , open-label study , 59 patients received a single dose of dabigatran etexilate , administered 1 to 3 hours following total hip replacement . In healthy volunteers , food had no effect on the extent of absorption of dabigatran etexilate , although there was reduced interindividual variability for dabigatran maximum plasma concentration and AUC(0-infinity ) . A decrease in the mean dabigatran AUC(0-infinity ) ( 904 to 705 ng*h/mL ) occurred with coadministration of pantoprazole . In patients undergoing total hip replacement , immediate onset of absorption was seen with the maximum plasma concentration of dabigatran occurring after 6 hours . The AUC(0 - 24 ) of dabigatran was 88 % of the steady-state AUC using a preliminary tablet formulation and 106 % of that seen in the healthy volunteer study . Compared with healthy volunteers , the postoperative profile was flattened with delayed peak concentrations . In summary , administration of the dabigatran etexilate capsule with food has no effect on the extent of dabigatran absorption , with a moderate decrease when coadministered with pantoprazole . Adequate plasma concentrations of dabigatran were seen with early postoperative administration of the dabigatran etexilate capsule . These pharmacokinetic characteristics confirm the suitability of this oral solid dosage form for use in future clinical trials BACKGROUND Edoxaban ( the free base of DU-176b ) is an oral , direct factor (F)Xa inhibitor in clinical development for the prevention and treatment of thromboembolic events . OBJECTIVES The aim of the present study was to evaluate the efficacy and safety of edoxaban for the prevention of venous thromboembolism ( VTE ) in patients undergoing total knee arthroplasty ( TKA ) . PATIENTS / METHODS This was a r and omized , double-blind , placebo-controlled , multicenter study conducted in Japan . A total of 523 Japanese patients were assigned to receive edoxaban 5 , 15 , 30 or 60 mg once daily or placebo for 11 - 14 days . A placebo control was used as neither low-molecular-weight heparin ( LMWH ) nor fondaparinux had been approved for thromboprophylaxis at the time of the study in Japan . The primary efficacy outcome was the incidence of VTE ( lower-extremity deep vein thrombosis , symptomatic pulmonary embolism or symptomatic deep vein thrombosis ) . The primary safety outcome was the incidence of major and clinical ly relevant non-major bleeding . RESULTS Edoxaban produced a significant dose-related reduction in VTE : the incidence of VTE was 29.5 % , 26.1 % , 12.5 % and 9.1 % in the edoxaban 5- , 15- , 30- and 60-mg treatment groups vs. 48.3 % in the placebo group . The incidence of major and clinical ly relevant non-major bleeding was similar across all groups without any significant differences among edoxaban doses or between edoxaban and placebo . CONCLUSIONS Edoxaban demonstrated significant dose-dependent reductions in VTE in patients undergoing TKA with a bleeding incidence similar to placebo . [ This trial is registered with JAPIC , JapicCTI-060283 ( ja ) . ] This trial compared the efficacy and safety of oral dabigatran , a direct thrombin inhibitor , versus subcutaneous enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . A total of 2,055 patients were r and omised to 28 - 35 days treatment with oral dabigatran , 220 mg once-daily , starting with a half-dose 1 - 4 hours after surgery , or subcutaneous enoxaparin 40 mg once-daily , starting the evening before surgery . The primary efficacy outcome was a composite of total venous thromboembolism [ VTE ] ( venographic or symptomatic ) and death from all-causes . The main secondary composite outcome was major VTE ( proximal deep-vein thrombosis or non-fatal pulmonary embolism ) plus VTE-related death . The main safety outcome was major bleeding . In total , 2,013 were treated , of whom 1,577 operated patients were included in the primary efficacy analysis . The primary efficacy outcome occurred in 7.7 % of the dabigatran group versus 8.8 % of the enoxaparin group , risk difference ( RD ) -1.1 % ( 95%CI -3.8 to 1.6 % ) ; p<0.0001 for the pre-specified non-inferiority margin . Major VTE plus VTE-related death occurred in 2.2 % of the dabigatran group versus 4.2 % of the enoxaparin group , RD -1.9 % ( -3.6 % to -0.2 % ) ; p=0.03 . Major bleeding occurred in 1.4 % of the dabigatran group and 0.9 % of the enoxaparin group ( p=0.40 ) . The incidence of adverse events , including liver enzyme elevations and cardiac events , during treatment was similar between the groups . Extended prophylaxis with oral dabigatran 220 mg once-daily was as effective as subcutaneous enoxaparin 40 mg once-daily in reducing the risk of VTE after total hip arthroplasty , and superior to enoxaparin for reducing the risk of major VTE . The risk of bleeding and safety profiles were similar BACKGROUND Prophylaxis for venous thromboembolism is recommended for at least 10 days after total knee arthroplasty ; oral regimens could enable shorter hospital stays . We aim ed to test the efficacy and safety of oral rivaroxaban for the prevention of venous thromboembolism after total knee arthroplasty . METHODS In a r and omised , double-blind , phase III study , 3148 patients undergoing knee arthroplasty received either oral rivaroxaban 10 mg once daily , beginning 6 - 8 h after surgery , or subcutaneous enoxaparin 30 mg every 12 h , starting 12 - 24 h after surgery . Patients had m and atory bilateral venography between days 11 and 15 . The primary efficacy outcome was the composite of any deep-vein thrombosis , non-fatal pulmonary embolism , or death from any cause up to day 17 after surgery . Efficacy was assessed as non-inferiority of rivaroxaban compared with enoxaparin in the per- protocol population ( absolute non-inferiority limit -4 % ) ; if non-inferiority was shown , we assessed whether rivaroxaban had superior efficacy in the modified intention-to-treat population . The primary safety outcome was major bleeding . This trial is registered with Clinical Trials.gov , number NCT00362232 . FINDINGS The primary efficacy outcome occurred in 67 ( 6.9 % ) of 965 patients given rivaroxaban and in 97 ( 10.1 % ) of 959 given enoxaparin ( absolute risk reduction 3.19 % , 95 % CI 0.71 - 5.67 ; p=0.0118 ) . Ten ( 0.7 % ) of 1526 patients given rivaroxaban and four ( 0.3 % ) of 1508 given enoxaparin had major bleeding ( p=0.1096 ) . INTERPRETATION Oral rivaroxaban 10 mg once daily for 10 - 14 days was significantly superior to subcutaneous enoxaparin 30 mg given every 12 h for the prevention of venous thromboembolism after total knee arthroplasty . FUNDING Bayer Schering Pharma AG , Johnson & Johnson Pharmaceutical Research & Development Dabigatran , an oral once-daily unmonitored thrombin inhibitor , has been tested elsewhere using enoxaparin 40 mg once daily . We used the North American enoxaparin 30 mg BID regimen as the comparator . This was a double-blind , central ly r and omized trial . Unilateral total knee arthroplasty patients were r and omized to receive oral dabigatran etexilate 220 or 150 mg once daily , or enoxaparin 30 mg SC BID after surgery , blinded . Dosing stopped at contrast venography , 12 to 15 days after surgery . Among 1896 patients , dabigatran 220 and 110 mg showed inferior efficacy to enoxaparin ( venous thromboembolism rates of 31 % [ P = .02 vs enoxaparin ] , 34 % [ P < .001 vs enoxaparin ] , and 25 % , respectively ) . Bleeding rates were similar , and no drug-related hepatic illness was recognized . Dabigatran , effective compared to once-daily enoxaparin , showed inferior efficacy to the twice-daily North American enoxaparin regimen , probably because of the latter 's more intense and prolonged dosing BACKGROUND We investigated the efficacy of rivaroxaban , an orally active direct factor Xa inhibitor , in preventing venous thrombosis after total knee arthroplasty . METHODS In this r and omized , double-blind trial , 2531 patients who were to undergo total knee arthroplasty received either oral rivaroxaban , 10 mg once daily , beginning 6 to 8 hours after surgery , or subcutaneous enoxaparin , 40 mg once daily , beginning 12 hours before surgery . The primary efficacy outcome was the composite of any deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause within 13 to 17 days after surgery . Secondary efficacy outcomes included major venous thromboembolism ( i.e. , proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death related to venous thromboembolism ) and symptomatic venous thromboembolism . The primary safety outcome was major bleeding . RESULTS The primary efficacy outcome occurred in 79 of 824 patients ( 9.6 % ) who received rivaroxaban and in 166 of 878 ( 18.9 % ) who received enoxaparin ( absolute risk reduction , 9.2 % ; 95 % confidence interval [ CI ] , 5.9 to 12.4 ; P<0.001 ) . Major venous thromboembolism occurred in 9 of 908 patients ( 1.0 % ) given rivaroxaban and 24 of 925 ( 2.6 % ) given enoxaparin ( absolute risk reduction , 1.6 % ; 95 % CI , 0.4 to 2.8 ; P=0.01 ) . Symptomatic events occurred less frequently with rivaroxaban than with enoxaparin ( P=0.005 ) . Major bleeding occurred in 0.6 % of patients in the rivaroxaban group and 0.5 % of patients in the enoxaparin group . The incidence of drug-related adverse events , mainly gastrointestinal , was 12.0 % in the rivaroxaban group and 13.0 % in the enoxaparin group . CONCLUSIONS Rivaroxaban was superior to enoxaparin for thromboprophylaxis after total knee arthroplasty , with similar rates of bleeding . ( Clinical Trials.gov number , NCT00361894 . Abstract Background and Objective : Dabigatran etexilate is an oral direct thrombin inhibitor in clinical development for the prevention and treatment of thromboembolic disorders . Following oral administration , dabigatran etexilate is rapidly absorbed and converted into its active form , dabigatran . The aim of this study was to investigate the effect of renal impairment on the pharmacokinetics and pharmacodynamics of dabigatran following administration of a single oral dose of dabigatran etexilate in subjects with renal impairment ( 150 mg ) or end-stage renal disease ( ESRD ) on maintenance haemodialysis ( 50 mg ) . Methods : This open-label , parallel-group , single-centre study enrolled 23 subjects with mild , moderate or severe renal impairment ( creatinine clearance > 50 to ≤80 , > 30 to ≤50 and ≤30 mL/min , respectively ) , 6 patients with ESRD and 6 healthy subjects . Blood and urine sample s were collected up to 96 hours after dosing for determination of dabigatran pharmacokinetic and pharmacodynamic parameters . Results : Compared with the values in healthy subjects , the area under the plasma concentration-time curve from time zero to infinity ( AUC∞ ) values were 1.5- , 3.2- and 6.3-fold higher in subjects with mild , moderate and severe renal impairment . Changes in the maximum plasma concentration ( Cmax ) were modest , and the time to reach the Cmax was unchanged . In subjects with severe renal impairment , the mean terminal elimination half-life was doubled ( 28 hours vs 14 hours for control ) . The AUC for prolongation of pharmacodynamic parameters ( the activated partial thromboplastin time and ecarin clotting time ) increased in line with the pharmacokinetic changes . In patients with ESRD , the dose-normalized AUC∞ was approximately twice the value in the control group . Haemodialysis removed 62–68 % of the dose . Dabigatran etexilate was well tolerated in all groups . Conclusions : Exposure to dabigatran is increased by renal impairment and correlates with the severity of renal dysfunction . A decrease in the dose and /or an increase in the administration interval in these patients may be appropriate . In patients with ESRD , dabigatran can be partly removed from the plasma by haemodialysis BACKGROUND Vitamin K antagonists have been shown to prevent stroke in patients with atrial fibrillation . However , many patients are not suitable c and i date s for or are unwilling to receive vitamin K antagonist therapy , and these patients have a high risk of stroke . Apixaban , a novel factor Xa inhibitor , may be an alternative treatment for such patients . METHODS In a double-blind study , we r and omly assigned 5599 patients with atrial fibrillation who were at increased risk for stroke and for whom vitamin K antagonist therapy was unsuitable to receive apixaban ( at a dose of 5 mg twice daily ) or aspirin ( 81 to 324 mg per day ) , to determine whether apixaban was superior . The mean follow up period was 1.1 years . The primary outcome was the occurrence of stroke or systemic embolism . RESULTS Before enrollment , 40 % of the patients had used a vitamin K antagonist . The data and safety monitoring board recommended early termination of the study because of a clear benefit in favor of apixaban . There were 51 primary outcome events ( 1.6 % per year ) among patients assigned to apixaban and 113 ( 3.7 % per year ) among those assigned to aspirin ( hazard ratio with apixaban , 0.45 ; 95 % confidence interval [ CI ] , 0.32 to 0.62 ; P<0.001 ) . The rates of death were 3.5 % per year in the apixaban group and 4.4 % per year in the aspirin group ( hazard ratio , 0.79 ; 95 % CI , 0.62 to 1.02 ; P=0.07 ) . There were 44 cases of major bleeding ( 1.4 % per year ) in the apixaban group and 39 ( 1.2 % per year ) in the aspirin group ( hazard ratio with apixaban , 1.13 ; 95 % CI , 0.74 to 1.75 ; P=0.57 ) ; there were 11 cases of intracranial bleeding with apixaban and 13 with aspirin . The risk of a first hospitalization for cardiovascular causes was reduced with apixaban as compared with aspirin ( 12.6 % per year vs. 15.9 % per year , P<0.001 ) . The treatment effects were consistent among important subgroups . CONCLUSIONS In patients with atrial fibrillation for whom vitamin K antagonist therapy was unsuitable , apixaban reduced the risk of stroke or systemic embolism without significantly increasing the risk of major bleeding or intracranial hemorrhage . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00496769 . ) BACKGROUND Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations . Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin . METHODS In this r and omized , double-blind trial , we compared apixaban ( at a dose of 5 mg twice daily ) with warfarin ( target international normalized ratio , 2.0 to 3.0 ) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke . The primary outcome was ischemic or hemorrhagic stroke or systemic embolism . The trial was design ed to test for noninferiority , with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause . RESULTS The median duration of follow-up was 1.8 years . The rate of the primary outcome was 1.27 % per year in the apixaban group , as compared with 1.60 % per year in the warfarin group ( hazard ratio with apixaban , 0.79 ; 95 % confidence interval [ CI ] , 0.66 to 0.95 ; P<0.001 for noninferiority ; P=0.01 for superiority ) . The rate of major bleeding was 2.13 % per year in the apixaban group , as compared with 3.09 % per year in the warfarin group ( hazard ratio , 0.69 ; 95 % CI , 0.60 to 0.80 ; P<0.001 ) , and the rates of death from any cause were 3.52 % and 3.94 % , respectively ( hazard ratio , 0.89 ; 95 % CI , 0.80 to 0.99 ; P=0.047 ) . The rate of hemorrhagic stroke was 0.24 % per year in the apixaban group , as compared with 0.47 % per year in the warfarin group ( hazard ratio , 0.51 ; 95 % CI , 0.35 to 0.75 ; P<0.001 ) , and the rate of ischemic or uncertain type of stroke was 0.97 % per year in the apixaban group and 1.05 % per year in the warfarin group ( hazard ratio , 0.92 ; 95 % CI , 0.74 to 1.13 ; P=0.42 ) . CONCLUSIONS In patients with atrial fibrillation , apixaban was superior to warfarin in preventing stroke or systemic embolism , caused less bleeding , and result ed in lower mortality . ( Funded by Bristol-Myers Squibb and Pfizer ; ARISTOTLE Clinical Trials.gov number , NCT00412984 . ) Background : Rivaroxaban ( BAY 59 - 7939 ) is a novel , oral , direct Factor Xa inhibitor in advanced clinical development for the prevention and treatment of thromboembolic disorders . Unwanted pro-arrhythmic effects are a common reason for drugs failing to gain regulatory approval ; these properties can be detected by assessing the effect of the drug on the QT interval . Objective : This study was performed , in accordance with International Conference on Harmonisation ( ICH ) E14 guidance , to assess whether rivaroxaban prolongs the QT interval . Study design : This was a prospect i ve , r and omized , double-blind , double-dummy , four-way crossover study . Setting : The study was conducted at a clinical pharmacology research unit . Subjects : Healthy male and female subjects ( n = 54 ) aged ≥50 years were enrolled and remained in the study unit for 3 days for each treatment . Of these , 50 patients were eligible for the QT analysis .Intervention : Subjects received single oral doses of rivaroxaban 45 mg or 15 mg , moxifloxacin 400 mg ( positive control ) , or placebo . Outcome measures : Multiple ECGs were taken at frequent intervals after drug administration , and the QT interval was measured manually under blinded conditions at a central laboratory . The Fridericia correction formula ( QTcF ) was used to correct the QT interval for heart rate . The primary outcome was the effect of rivaroxaban or moxifloxacin on the placebo-subtracted QTcF 3 hours after administration . The frequency of outlying QTcF values and the tolerability of the treatments were also assessed . Results : All treatments were well tolerated and had no effect on heart rate . Moxifloxacin established the required assay sensitivity ; placebo-subtracted QTcF 3 hours after moxifloxacin administration was prolonged by 9.77 ms ( 95 % CI 7.39 , 12.15 ) . Placebo-subtracted QTcF values 3 hours after rivaroxaban administration were −0.91 ms ( 95 % CI −3.33 , 1.52 ) and −1.83 ms ( 95 % CI −4.19 , 0.54 ) with rivaroxaban 45 mg and 15 mg , respectively . QTcF was not prolonged with rivaroxaban at any time , and the frequency of outlying results with rivaroxaban and placebo was similar . Conclusion : This thorough QT study , which was performed in accordance with ICH E14 guidelines , shows that rivaroxaban does not prolong the QTc interval . Therefore , the potential of rivaroxaban for the prevention and treatment of thromboembolic disorders , including chronic cardiovascular disorders , can be investigated in appropriate clinical studies without the need for intensive monitoring of the QTc interval BACKGROUND Low-molecular-weight heparins such as enoxaparin are preferred for prevention of venous thromboembolism after major joint replacement . Apixaban , an orally active factor Xa inhibitor , might be as effective , have lower bleeding risk , and be easier to use than is enoxaparin . We assessed efficacy and safety of these drugs after elective total knee replacement . METHODS In ADVANCE-2 , a multicentre , r and omised , double-blind phase 3 study , patients undergoing elective unilateral or bilateral total knee replacement were r and omly allocated through an interactive central telephone system to receive oral apixaban 2.5 mg twice daily ( n=1528 ) or subcutaneous enoxaparin 40 mg once daily ( 1529 ) . The r and omisation schedule was generated by the Bristol-Myers Squibb r and omisation centre and stratified by study site and by unilateral or bilateral surgery with a block size of four . Investigators , patients , statisticians , adjudicators , and steering committee were masked to allocation . Apixaban was started 12 - 24 h after wound closure and enoxaparin 12 h before surgery ; both drugs were continued for 10 - 14 days , when bilateral ascending venography was scheduled . Primary outcome was the composite of asymptomatic and symptomatic deep vein thrombosis , non-fatal pulmonary embolism , and all-cause death during treatment . The statistical plan required non-inferiority of apixaban before testing for superiority ; analysis was by intention to treat for non-inferiority testing . The study is registered at Clinical Trials.gov , number NCT00452530 . FINDINGS 1973 of 3057 patients allocated to treatment ( 1528 apixaban , 1529 enoxaparin ) were eligible for primary efficacy analysis . The primary outcome was reported in 147 ( 15 % ) of 976 apixaban patients and 243 ( 24 % ) of 997 enoxaparin patients ( relative risk 0.62 [ 95 % CI 0.51 - 0.74 ] ; p<0.0001 ; absolute risk reduction 9.3 % [ 5.8 - 12.7 ] ) . Major or clinical ly relevant non-major bleeding occurred in 53 ( 4 % ) of 1501 patients receiving apixaban and 72 ( 5 % ) of 1508 treated with enoxaparin ( p=0.09 ) . INTERPRETATION Apixaban 2.5 mg twice daily , starting on the morning after total knee replacement , offers a convenient and more effective orally administered alternative to 40 mg per day enoxaparin , without increased bleeding . FUNDING Bristol-Myers Squibb ; Pfizer BACKGROUND This phase 3 trial compared the efficacy and safety of rivaroxaban , an oral direct inhibitor of factor Xa , with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty . METHODS In this r and omized , double-blind study , we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily , beginning after surgery , or 40 mg of enoxaparin subcutaneously once daily , beginning the evening before surgery , plus a placebo tablet or injection . The primary efficacy outcome was the composite of deep-vein thrombosis ( either symptomatic or detected by bilateral venography if the patient was asymptomatic ) , nonfatal pulmonary embolism , or death from any cause at 36 days ( range , 30 to 42 ) . The main secondary efficacy outcome was major venous thromboembolism ( proximal deep-vein thrombosis , nonfatal pulmonary embolism , or death from venous thromboembolism ) . The primary safety outcome was major bleeding . RESULTS A total of 3153 patients were included in the superiority analysis ( after 1388 exclusions ) , and 4433 were included in the safety analysis ( after 108 exclusions ) . The primary efficacy outcome occurred in 18 of 1595 patients ( 1.1 % ) in the rivaroxaban group and in 58 of 1558 patients ( 3.7 % ) in the enoxaparin group ( absolute risk reduction , 2.6 % ; 95 % confidence interval [ CI ] , 1.5 to 3.7 ; P<0.001 ) . Major venous thromboembolism occurred in 4 of 1686 patients ( 0.2 % ) in the rivaroxaban group and in 33 of 1678 patients ( 2.0 % ) in the enoxaparin group ( absolute risk reduction , 1.7 % ; 95 % CI , 1.0 to 2.5 ; P<0.001 ) . Major bleeding occurred in 6 of 2209 patients ( 0.3 % ) in the rivaroxaban group and in 2 of 2224 patients ( 0.1 % ) in the enoxaparin group ( P=0.18 ) . CONCLUSIONS A once-daily , 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily , 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty . The two drugs had similar safety profiles . ( Clinical Trials.gov number , NCT00329628 . BACKGROUND The optimal strategy for thromboprophylaxis after major joint replacement has not been established . Low-molecular-weight heparins such as enoxaparin predominantly target factor Xa but to some extent also inhibit thrombin . Apixaban , a specific factor Xa inhibitor , may provide effective thromboprophylaxis with a low risk of bleeding and improved ease of use . METHODS In a double-blind , double-dummy study , we r and omly assigned patients undergoing total knee replacement to receive 2.5 mg of apixaban orally twice daily or 30 mg of enoxaparin subcutaneously every 12 hours . Both medications were started 12 to 24 hours after surgery and continued for 10 to 14 days . Bilateral venography was then performed . The primary efficacy outcome was a composite of asymptomatic and symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , and death from any cause during treatment . Patients were followed for 60 days after anticoagulation therapy was stopped . RESULTS A total of 3195 patients underwent r and omization , with 1599 assigned to the apixaban group and 1596 to the enoxaparin group ; 908 subjects were not eligible for the efficacy analysis . The overall rate of primary events was much lower than anticipated . The rate of the primary efficacy outcome was 9.0 % with apixaban as compared with 8.8 % with enoxaparin ( relative risk , 1.02 ; 95 % confidence interval , 0.78 to 1.32 ) . The composite incidence of major bleeding and clinical ly relevant nonmajor bleeding was 2.9 % with apixaban and 4.3 % with enoxaparin ( P=0.03 ) . CONCLUSIONS As compared with enoxaparin for efficacy of thromboprophylaxis after knee replacement , apixaban did not meet the prespecified statistical criteria for noninferiority , but its use was associated with lower rates of clinical ly relevant bleeding and it had a similar adverse-event profile . ( Clinical Trials.gov number , NCT00371683 . BACKGROUND There are various regimens for thromboprophylaxis after hip replacement . Low-molecular-weight heparins such as enoxaparin predominantly inhibit factor Xa but also inhibit thrombin to some degree . Orally active , specific factor Xa inhibitors such as apixaban may provide effective thromboprophylaxis with a lower risk of bleeding and improved ease of use . METHODS In this double-blind , double-dummy study , we r and omly assigned 5407 patients undergoing total hip replacement to receive apixaban at a dose of 2.5 mg orally twice daily or enoxaparin at a dose of 40 mg subcutaneously every 24 hours . Apixaban therapy was initiated 12 to 24 hours after closure of the surgical wound ; enoxaparin therapy was initiated 12 hours before surgery . Prophylaxis was continued for 35 days after surgery , followed by bilateral venographic studies . The primary efficacy outcome was the composite of asymptomatic or symptomatic deep-vein thrombosis , nonfatal pulmonary embolism , or death from any cause during the treatment period . Patients were followed for an additional 60 days after the last intended dose of study medication . RESULTS A total of 1949 patients in the apixaban group ( 72.0 % ) and 1917 patients in the enoxaparin group ( 71.0 % ) could be evaluated for the primary efficacy analysis . The primary efficacy outcome occurred in 27 patients in the apixaban group ( 1.4 % ) and in 74 patients in the enoxaparin group ( 3.9 % ) ( relative risk with apixaban , 0.36 ; 95 % confidence interval [ CI ] , 0.22 to 0.54 ; P<0.001 for both noninferiority and superiority ; absolute risk reduction , 2.5 percentage points ; 95 % CI , 1.5 to 3.5 ) . The composite outcome of major and clinical ly relevant nonmajor bleeding occurred in 129 of 2673 patients assigned to apixaban ( 4.8 % ) and 134 of 2659 assigned to enoxaparin ( 5.0 % ) ( absolute difference in risk , -0.2 percentage points ; 95 % CI , -1.4 to 1.0 ) . CONCLUSIONS Among patients undergoing hip replacement , thromboprophylaxis with apixaban , as compared with enoxaparin , was associated with lower rates of venous thromboembolism , without increased bleeding . ( Funded by Bristol-Myers Squibb and Pfizer ; Clinical Trials.gov number , NCT00423319 . ) BACKGROUND Vitamin K antagonists have been the st and ard oral antithrombotic used for more than a half century for prevention and treatment of thromboembolism . Their limitations include multiple food and drug interactions and need for frequent monitoring and dose adjustments . Edoxaban is a selective and direct factor Xa inhibitor that may provide effective , safe , and more convenient anticoagulation . STUDY DESIGN ENGAGE AF-TIMI 48 is a phase 3 , r and omized , double-blind , double-dummy , multinational , noninferiority design megatrial comparing 2 exposure strategies of edoxaban to warfarin . Approximately 20,500 subjects will be r and omized to edoxaban high exposure ( 60 mg daily , adjusted for drug clearance ) , edoxaban low exposure ( 30 mg daily , adjusted for drug clearance ) , or warfarin titrated to an international normalized ratio of 2.0 to 3.0 . The edoxaban strategies provide for dynamic dose reductions in subjects with anticipated increased drug exposure . Blinded treatment is maintained through the use of sham international normalized ratios in patients receiving edoxaban . Eligibility criteria include electrical documentation of atrial fibrillation ≤12 months and a CHADS(2 ) score ≥2 . R and omization is stratified by CHADS(2 ) score and anticipated drug exposure . The primary objective is to determine whether edoxaban is noninferior to warfarin for the prevention of stroke and systemic embolism . The primary safety end point is modified International Society on Thrombosis and Haemostasis major bleeding . Recruitment began in November 2008 . The expected median follow-up is 24 months . CONCLUSIONS ENGAGE AF-TIMI 48 is a phase 3 comparison of the novel oral factor Xa inhibitor edoxaban to warfarin for the prevention of thromboembolism in patients with atrial fibrillation BACKGROUND The risk of venous thromboembolism is high after total hip arthroplasty and could persist after hospital discharge . Our aim was to compare the use of rivaroxaban for extended thromboprophylaxis with short-term thromboprophylaxis with enoxaparin . METHODS 2509 patients scheduled to undergo elective total hip arthroplasty were r and omly assigned , stratified according to centre , with a computer-generated r and omisation code , to receive oral rivaroxaban 10 mg once daily for 31 - 39 days ( with placebo injection for 10 - 14 days ; n=1252 ) , or enoxaparin 40 mg once daily subcutaneously for 10 - 14 days ( with placebo tablet for 31 - 39 days ; n=1257 ) . The primary efficacy outcome was the composite of deep-vein thrombosis ( symptomatic or asymptomatic detected by m and atory , bilateral venography ) , non-fatal pulmonary embolism , and all-cause mortality up to day 30 - 42 . Analyses were done in the modified intention-to-treat population , which consisted of all patients who had received at least one dose of study medication , had undergone planned surgery , and had adequate assessment of thromboembolism . This study is registered at Clinical Trials.gov , number NCT00332020 . FINDINGS The modified intention-to-treat population for the analysis of the primary efficacy outcome consisted of 864 patients in the rivaroxaban group and 869 in the enoxaparin group . The primary outcome occurred in 17 ( 2.0 % ) patients in the rivaroxaban group , compared with 81 ( 9.3 % ) in the enoxaparin group ( absolute risk reduction 7.3 % , 95 % CI 5.2 - 9.4 ; p<0.0001 ) . The incidence of any on-treatment bleeding was much the same in both groups ( 81 [ 6.6 % ] events in 1228 patients in the rivaroxaban safety population vs 68 [ 5.5 % ] of 1229 patients in the enoxaparin safety population ; p=0.25 ) . INTERPRETATION Extended thromboprophylaxis with rivaroxaban was significantly more effective than short-term enoxaparin plus placebo for the prevention of venous thromboembolism , including symptomatic events , in patients undergoing total hip arthroplasty |
12,848 | 29,346,146 | : Because of several methodology flaws in the review ed studies , these results suggest that there is currently no research evidence to suggest that the use of ORC+C improves wound healing rates of DFUs . | OBJECTIVE : Diabetic wounds that do not heal completely usually exhibit inflammatory markers , increased protease activity , and reduced levels of growth factors and cell count .
A systematic review was performed to determine whether there is enough evidence to support the use of an oxidized regenerated cellulose/collagen matrix ( ORC+C ) to treat diabetic foot ulcers ( DFUs ) . | Themicrocirculation of the wound bed is a key parameter for improving granulation tissue formation and , hence , wound healing . The aim of this study was to determine whether a wound dressing comprising collagen/oxidized regenerated cellulose has effects over a short term on wound healing . Wounds were evaluated using a clinical wound score ; pain associated with wounds was measured using a visual analogue scale . Wound microcirculation was evaluated using a technique based on noncontact remission spectroscopy . A prospect i ve trial was performed in 40 patients with chronic venous leg ulcers ( mean age 74 years ; range , 43 - 93 years ; 25 females and 15 males ) . Patients in group A were treated with PROMOGRAN ® Matrix ( Johnson & Johnson , New Brunswick , NJ ) combined with “ good ” ulcer care for 2 weeks . Control group B consisted of 10 patients who received only good ulcer care . The authors measured a favorable clinical response in 76.9 % ( group A ) versus 66.7 % ( group B ) . Themean reduction of ulcer area was statistically significant in group A ( P < .05 ) . The wound score improved in group A from 2.28 ± 1.24 ( before treatment ) increasing to 3.72 ± 1.57 ( after 1 week ; P < .00023 ) and 4.92 ± 1.68 ( after 2 weeks ; P < .000027 ) . In group B , the score improved from 1.44 ± 1.33 ( before treatment ) to 3.22 ± 1.30 ( after 1 week ; P < .0077 ) . The mean visual analogue pain score before treatment was 8.72 ( group A ) and 7.88 ( group B ) ( ns , P > .05 ) . After 1 week of treatment , the score dropped to 5.76 ( group A ) and 6.66 ( group B ) . In the second week , group A patients had a mean pain score of 3.84 compared with the pain score before treatment ( P < .05 ) . After 1 week of treatment , in group A there was a decrease in remission spectroscopy , which is considered to reflect an improvement in microcirculation This study tests the hypothesis that addition of a protease-modulating matrix enhances the efficacy of autologous growth factors in diabetic ulcers . Fifty-one patients with chronic diabetic foot ulcers were managed as out patients at the Democritus University Hospital of Alex and roupolis and followed up for 8 weeks . All target ulcers were > or = 2.5 cm in any one dimension and had been previously treated only with moist gauze . Patients were r and omly allocated in three groups of 17 patients each : Group A was treated only with the oxidized regenerated cellulose/collagen bio material ( Promogran , Johnson & Johnson , New Brunswick , NJ ) , Group B was treated only with autologous growth factors delivered by Gravitational Platelet Separation System ( GPS , Biomet ) , and Group C was managed by a combination of both . All ulcers were digitally photographed at initiation of the study and then at change of dressings once weekly . Computerized planimetry ( Texas Health Science Center ImageTool , Version 3.0 ) was used to assess ulcer dimensions that were analyzed for homogeneity and significance using the Statistical Package for Social Sciences , Version 13.0 . Post hoc analysis revealed that there was significantly greater reduction of all three dimensions of the ulcers in Group C compared to Groups A and B ( all P<.001 ) . Although reduction of ulcer dimensions was greater in Group A than in Group B , these differences did not reach statistical significance . It is concluded that protease-modulating dressings act synergistically with autologous growth factors and enhance their efficacy in diabetic foot ulcers Health care professionals are increasingly required to base clinical decisions on the best available evidence . Evidence based medicine ( EBM ) is a systematic approach to clinical problem solving which allows the integration of the best available research evidence with clinical expertise and patient values . This paper explains the concept of EBM and introduces the five step EBM model : formulation of answerable clinical questions ; search ing for evidence ; critical appraisal ; applicability of evidence ; evaluation of performance . Subsequent articles will focus on the principles and critical appraisal of r and omised controlled trials , systematic review s , and meta-analyses , and provide a practical demonstration of the five step EBM model using a real life clinical scenario HYPOTHESIS Promogran , a wound dressing consisting of collagen and oxidized regenerated cellulose , is more effective that st and ard care in treating chronic diabetic plantar ulcers . DESIGN R and omized , prospect i ve , controlled multicenter trial . SETTING University teaching hospitals and primary care centers . PATIENTS A total of 276 patients from 11 centers were enrolled in the study . The mean age of the patients was 58.3 years ( range , 23 - 85 years ) . All patients had at least 1 diabetic foot ulcer . INTERVENTIONS Patients were r and omized to receive Promogran ( n = 138 ) or moistened gauze ( control group ; n = 138 ) and a secondary dressing . Dressings were changed when clinical ly required . The maximum follow-up for each patient was 12 weeks . MAIN OUTCOME MEASURE Complete healing of the study ulcer ( wound ) . RESULTS After 12 weeks of treatment , 51 ( 37.0 % ) Promogran-treated patients had complete wound closure compared with 39 ( 28.3 % ) control patients s , but this difference was not statistically significant ( P = .12 ) . The difference in healing between treatment groups achieved borderline significance in the subgroup of patients with wounds of less than 6 months ' duration . In patients with ulcers of less than 6 months ' duration , 43 ( 45 % ) of 95 Promogran-treated patients healed compared with 29 ( 33 % ) of 89 controls ( P = .056 ) . In the group with wounds of at least 6 months ' duration , similar numbers of patients healed in the control ( 10/49 [ 20 % ] ) and the Promogran ( 8/43 [ 19 % ] ; P = .83 ) groups . No differences were seen in the safety measurements between groups . Patients and investigators expressed a strong preference for Promogran compared with moistened gauze . CONCLUSIONS Promogran was comparable to moistened gauze in promoting wound healing in diabetic foot ulcers . It showed an additional efficacy for ulcers of less than 6 months ' duration that was of marginal statistical significance . Furthermore , Promogran had a safety profile that was similar to that of moistened gauze , with greater user satisfaction . Therefore , Promogran may be a useful adjunct in the management of diabetic foot ulceration , especially in ulcers of less than 6 months ' duration Collagen/oxidized regenerated cellulose (ORC)/silver therapy has been design ed to facilitate wound healing by normalizing the microenvironment and correcting biochemical imbalances in chronic wounds . The aim of this study was to compare collagen/ORC/silver therapy to control ( st and ard treatment ) . Patients with diabetic foot ulcers were r and omized to either collagen/ORC/silver ( 24 ) or control treatment ( 15 ) . Wound area measurements and wound fluid sample s were taken weekly . Protease levels were measured in wound fluid sample s to investigate differences between responders ( ≥50 % reduction in wound area by week 4 ) and nonresponders ( < 50 % reduction in wound area by week 4 ) . There were significantly more responders in the collagen/ORC/silver group compared with the control group ( 79 % vs. 43 % , p = 0.035 ) . There were significantly fewer withdrawals from the study because of infection in the collagen/ORC/silver group compared with the control group ( 0 % vs. 31 % , p = 0.012 ) . The sum of matrix metalloproteinase-9 and elastase concentration was higher in nonresponders compared with responders at baseline ( p = 0.0705 ) and week 4 ( p = 0.012 ) . The results suggest that collagen/ORC/silver normalizes the wound microenvironment and protects against infection , result ing in improved wound healing . It was also demonstrated that measuring a combination of proteases may be a more relevant prognostic healing marker than any individual protease alone The inadequacy of most of traditional sources for medical information , like textbook and review article , do not sustained the clinical decision based on the best evidence current available , exposing the patient to a unnecessary risk . Although not integrated around clinical problem areas in the convenient way of textbooks , current best evidence from specific studies of clinical problems can be found in an increasing number of Internet and electronic data bases . The sources that have already undergone rigorous critical appraisal are classified as secondary information sources , others that provide access to original article or abstract , as primary information source , where the quality assessment of the article rely on the clinician oneself . The most useful primary information source are SciELO , the online collection of Brazilian scientific journals , and Medline , the most comprehensive data base of the USA National Library of Medicine , where the search may start with use of keywords , that were obtained at the structured answer construction ( P.I.C.O. ) , with the addition of boolean operators " AND " , " OR " , " NOT " . Between the secondary information sources , some of them provide critically appraised articles , like ACP Journal Club , Evidence Based Medicine and InfoPOEMs , others provide evidence s organized as online texts , such as " Clinical Evidence " and " UpTo Date " , and finally , Cochrane Library are composed by systematic review s of r and omized controlled trials . To get studies that could answer the clinical question is part of a mindful practice , that is , becoming quicker and quicker and dynamic with the use of PDAs , Palmtops and Notebooks INTRODUCTION Diabetic foot is a complication of diabetes mellitus that manifests with the development of ulcers that frequently precede amputation . Several studies have verified that the environment of the diabetic neuropathic foot ulcer contains a high concentration of metalloproteinases . The aim of the present study was to evaluate the efficacy of a protease-modulating dressing in the treatment of neuropathic diabetic foot ulcers . MATERIAL AND METHOD A r and omized controlled trial was conducted in 40 patients with a 6-week or longer history of neuropathic diabetic foot ulcer . The patients were r and omized to two groups : group 1 ( n = 20 ) received treatment with the protease-modulating dressing while the control group ( group 2 ; n = 20 ) received the treatment specified in the st and ardized protocol for good wound care . The patients were then followed-up for 6 weeks . RESULTS After 6 weeks , healing was achieved in 12 patients ( 63 % of n = 19 ) in group 1 under treatment with the protease-modulating dressing versus three patients ( 15 % of n = 19 ) in the control group ( p < 0.03 ) . The mean time to healing was 23.3 + /- 9.9 days in group 1 and 40.6 + /- 1.15 days in group 2 ( p < 0.01 ) . CONCLUSIONS The results confirm the hypothesis that the use of protease-modulating dressings in patients with neuropathic diabetic foot ulcers leads to better tissue regeneration than good wound care |
12,849 | 19,248,931 | Conclusion : Tonsillectomy reduces the incidence of recurrent pharyngitis to a modest degree | Objective : To determine the evidence for efficacy of tonsillectomy in reducing the incidence of recurrent pharyngitis . | OBJECTIVE To evaluate the cost-effectiveness of adenotonsillectomy compared with watchful waiting in Dutch children . DESIGN Economic evaluation along with an open , r and omized , controlled trial . SETTING Multicenter , including 21 general and 3 university hospitals in the Netherl and s. PARTICIPANTS Three hundred children aged 2 to 8 years were selected for adenotonsillectomy according to routine medical practice . Excluded were children who had frequent throat infections and those with suspected obstructive sleep apnea . MAIN OUTCOME MEASURES Incremental cost-effectiveness in terms of costs per episode of fever , throat infection , and upper respiratory tract infection avoided . RESULTS Annual costs incurred in the adenotonsillectomy group were euro803 ( the average exchange rate for the US dollar in 2002 was $ 1.00 = euro1.1 , except toward the end of 2002 when $ 0.95 = euro100 ) and euro551 in the watchful waiting group ( 46 % increase ) . During a median follow-up of 22 months , surgery compared with watchful waiting reduced the number of episodes of fever and throat infections by 0.21 per person-year ( 95 % confidence interval , -0.12 to 0.54 and 0.06 to 0.36 , respectively ) and upper respiratory tract infections by 0.53 ( 95 % confidence interval , 0.08 to 0.97 ) episodes . The incremental costs per episode avoided were euro1136 , euro1187 , and euro465 , respectively . CONCLUSIONS In children undergoing adenotonsillectomy because of mild to moderate symptoms of throat infections or adenotonsillar hypertrophy , surgery result ed in a significant increase in costs without realizing relevant clinical benefit . Subgroups of children in whom surgery would be cost-effective may be identified in further research . We studied the efficacy of tonsillectomy , or tonsillectomy with adenoidectomy , in 187 children severely affected with recurrent throat infection . Ninety-one of the children were assigned r and omly to either surgical or nonsurgical treatment groups , and 96 were assigned according to parental preference . In both the r and omized and nonr and omized trials , the effects of tonsillectomy and of tonsillectomy with adenoidectomy were similar . By various measures , the incidence of throat infection during the first two years of follow-up was significantly lower ( P less than or equal to 0.05 ) in the surgical groups than in the corresponding nonsurgical groups . Third-year differences , although in most cases not significant , also consistently favored the surgical groups . On the other h and , in each follow-up year many subjects in the nonsurgical groups had fewer than three episodes of infection , and most episodes among subjects in the nonsurgical groups were mild . Of the 95 subjects treated with surgery , 13 ( 14 per cent ) had surgery-related complications , all of which were readily managed or self-limited . These results warrant the election of tonsillectomy for children meeting the trials ' stringent eligibility criteria , but also provide support for nonsurgical management . Treatment for such children must therefore be individualized OBJECTIVE In previous clinical trials involving children severely affected with recurrent throat infection ( 7 or more well-documented , clinical ly important , adequately treated episodes of throat infection in the preceding year , or 5 or more such episodes in each of the 2 preceding years , or 3 or more such episodes in each of the 3 preceding years ) , we found tonsillectomy efficacious in reducing the number and severity of subsequent episodes of throat infection for at least 2 years . The results seemed to warrant the election of tonsillectomy in children meeting the trials ' stringent eligibility criteria but also provided support for nonsurgical management . We undertook the present trials to determine 1 ) whether tonsillectomy would afford equivalent benefit in children who were less severely affected than those in our earlier trials but who nonetheless had indications for tonsillectomy comparable to those in general use , and 2 ) whether , in such children , the addition of adenoidectomy would confer additional benefit . METHODS We conducted 2 parallel r and omized , controlled trials in the Ambulatory Care Center of Children 's Hospital of Pittsburgh . To be eligible , children were required to have had a history of recurrent episodes of throat infection that met st and ards slightly less stringent than the st and ards used in our earlier trials regarding either the frequency of previous episodes or their clinical features or their degree of documentation , but not regarding > 1 of those parameters . These reduced st and ards were nonetheless more stringent than those in current official guidelines , which list " 3 or more infections of tonsils and /or adenoids per year despite adequate medical therapy " as an indication for tonsillectomy or adenotonsillectomy . Of 2174 children referred by physicians or parents , 373 met the current trials ' eligibility criteria and 328 were enrolled . Of these , 177 children without obstructing adenoids or recurrent or persistent otitis media were r and omized to either a tonsillectomy group , an adenotonsillectomy group , or a control group ( the 3-way trial ) , and 151 children who had 1 or more such conditions were r and omized to either an adenotonsillectomy group or a control group ( the 2-way trial ) . Outcome measures were the occurrence of episodes of throat infection during the 3 years of follow-up ; other , indirect measures of morbidity ; and complications of surgery . RESULTS By various measures , the incidence of throat infection was significantly lower in surgical groups than in corresponding control groups during each of the 3 follow-up years . However , even among control children , mean rates of moderate or severe episodes were low , ranging from 0.16 to 0.43 per year . Adenotonsillectomy was no more efficacious than tonsillectomy alone . Of 203 children treated with surgery , 16 ( 7.9 % ) had surgery-related complications of varying types and severity . CONCLUSIONS The modest benefit conferred by tonsillectomy or adenotonsillectomy in children moderately affected with recurrent throat infection seems not to justify the inherent risks , morbidity , and cost of the operations . We conclude that , under ordinary circumstances , neither eligibility criteria such as those used for the present trials nor the criterion for surgery in current official guidelines are sufficiently stringent for use in clinical practice A prospect i ve study comparing surgical and antibiotic treatment for recurrent tonsillitis in adults suggests that , whilst tonsillectomy is very effective , adequate medical treatment provides an equally good alternative in the majority of patients |
12,850 | 25,448,853 | RESULTS Of the 30 neurophysiological outcome measures reported by at least two different research groups , tDCS was found to have a reliable effect on only one : MEP amplitude .
Interestingly , the magnitude of this effect has been significantly decreasing over the last 14 years . | BACKGROUND Transcranial direct current stimulation ( tDCS ) is a form of neuromodulation that is increasingly being utilized to examine and modify a number of cognitive and behavioral measures .
The theoretical mechanisms by which tDCS generates these changes are predicated upon a rather large neurophysiological literature .
However , a robust systematic review of this neurophysiological data has not yet been undertaken . | Transcranial direct current stimulation ( tDCS ) was recently reintroduced as a tool for inducing relatively long-lasting changes in cortical excitability in focal brain regions . Anodal stimulation over the primary motor cortex enhances cortical excitability , whereas cathodal stimulation decreases it . Prior studies have shown that enhancement of D2 receptor activity by pergolide consoli date s tDCS-generated excitability diminution for up to 24 hours and that cathodal stimulation of the primary motor cortex diminishes experimentally induced pain sensation and reduces the N2-P2 amplitude of laser-evoked potentials immediately poststimulation . In the present study , we investigated the effect of pergolide and cathodal tDCS over the primary motor cortex on laser-evoked potentials and acute pain perception induced with a Tm : YAG laser in a double-blind , r and omized , placebo-controlled , crossover study . The amplitude changes of laser-evoked potentials and subjective pain rating scores of 12 healthy subjects were analyzed prior to and following 15 minutes cathodal tDCS combined with pergolide or placebo intake at five different time points . Our results indicate that the amplitude of the N2 component was significantly reduced following cathodal tDCS for up to two hours . Additionally , pergolide prolonged the effect of the cathodal tDCS for up to 24 hours , and a significantly lowered pain sensation was observed for up to 40 minutes . Our study is a further step toward clinical application of cathodal tDCS over the primary motor cortex using pharmacological intervention to prolong the excitability-diminishing effect on pain perception for up to 24 hours poststimulation . Furthermore , it demonstrates the potential for repetitive daily stimulation therapy for pain patients Transcranial direct current stimulation ( tDCS ) of the human motor cortex results in polarity-specific shifts of cortical excitability during and after stimulation . Anodal tDCS enhances and cathodal stimulation reduces excitability . Animal experiments have demonstrated that the effect of anodal tDCS is caused by neuronal depolarisation , while cathodal tDCS hyperpolarises cortical neurones . However , not much is known about the ion channels and receptors involved in these effects . Thus , the impact of the sodium channel blocker carbamazepine , the calcium channel blocker flunarizine and the NMDA receptor antagonist dextromethorphane on tDCS-elicited motor cortical excitability changes of healthy human subjects were tested . tDCS- protocol s inducing excitability alterations ( 1 ) only during tDCS and ( 2 ) eliciting long-lasting after-effects were applied after drug administration . Carbamazepine selectively eliminated the excitability enhancement induced by anodal stimulation during and after tDCS . Flunarizine result ed in similar changes . Antagonising NMDA receptors did not alter current-generated excitability changes during a short stimulation , which elicits no after-effects , but prevented the induction of long-lasting after-effects independent of their direction . These results suggest that , like in other animals , cortical excitability shifts induced during tDCS in humans also depend on membrane polarisation , thus modulating the conductance of sodium and calcium channels . Moreover , they suggest that the after-effects may be NMDA receptor dependent . Since NMDA receptors are involved in neuroplastic changes , the results suggest a possible application of tDCS in the modulation or induction of these processes in a clinical setting . The selective elimination of tDCS-driven excitability enhancements by carbamazepine proposes a role for this drug in focussing the effects of cathodal tDCS , which may have important future clinical applications Background Preventive pharmacotherapy for migraine is not satisfactory because of the low efficacy/tolerability ratio of many available drugs . Novel and more efficient preventive strategies are therefore warranted . Abnormal excitability of cortical areas appears to play a pivotal role in migraine pathophysiology . Transcranial direct current stimulation ( tDCS ) is a non-invasive and safe technique that is able to durably modulate the activity of the underlying cerebral cortex , and is being tested in various medical indications . The results of small open studies using tDCS in migraine prophylaxis are conflicting , possibly because the optimal stimulation setting s and the brain targets were not well chosen . We have previously shown that the cerebral cortex , especially the visual cortex , is hyperresponsive in migraine patients between attacks and provided evidence from evoked potential studies that this is due to a decreased cortical preactivation level . If one accepts this concept , anodal tDCS over the visual cortex may have therapeutic potentials in migraine prevention , as it is able to increase neuronal firing . Objective To study the effects of anodal tDCS on visual cortex activity in healthy volunteers ( HV ) and episodic migraine without aura patients ( MoA ) , and its potentials for migraine prevention . Methods We recorded pattern-reversal visual evoked potentials ( VEP ) before and after a 15-min session of anodal tDCS over the visual cortex in 11 HV and 13 MoA interictally . Then 10 MoA patients reporting at least 4 attacks/month subsequently participated in a therapeutic study , and received 2 similar sessions of tDCS per week for 8 weeks as migraine preventive therapy . Results In HV as well as in MoA , anodal tDCS transiently increased habituation of the VEP N1P1 component . VEP amplitudes were not modified by tDCS . Preventive treatment with anodal tDCS turned out to be beneficial in MoA : migraine attack frequency , migraine days , attack duration and acute medication intake significantly decreased during the treatment period compared to pre-treatment baseline ( all p < 0.05 ) , and this benefit persisted on average 4.8 weeks after the end of tDCS . Conclusions Anodal tDCS over the visual cortex is thus able to increase habituation to repetitive visual stimuli in healthy volunteers and in episodic migraineurs , who on average lack habituation interictally . Moreover , 2 weekly sessions of anodal tDCS had a significant preventive anti- migraine effect , proofing the concept that the low preactivation level of the visual cortex in migraine patients can be corrected by an activating neurostimulation . The therapeutic results indicate that a larger sham-controlled trial using the same tDCS protocol is worthwhile Transcranial DC stimulation ( tDCS ) is a plasticity-inducing noninvasive brain stimulation tool with various potential therapeutic applications in neurological and psychiatric diseases . Currently , the duration of the aftereffects of stimulation is restricted . For future clinical applications , stimulation protocol s are required that produce aftereffects lasting for days or weeks . Options to prolong the effects of tDCS are further prolongation or repetition of tDCS . Nothing is known thus far about optimal protocol s in this behalf , although repetitive stimulation is already performed in clinical applications . Thus we explored the effects of different break duration s on cathodal tDCS-induced cortical excitability alterations . In 12 subjects , two identical periods of cathodal tDCS ( 9-min duration ; 1 mA ) with an interstimulation interval of 0 ( no break ) , 3 , or 20 min or 3 or 24 h were performed . The results indicate that doubling stimulation duration without a break prolongs the aftereffects from 60 to 90 min after tDCS . When the second stimulation was performed during the aftereffects of the first , a prolongation and enhancement of tDCS-induced effects for ≤ 120 min after stimulation was observed . In contrast , when the second stimulation followed the first one after 3 or 24 h , the aftereffects were initially attenuated , or abolished , but afterwards re-established for up to 120 min after tDCS in the 24-h condition . These results suggest that , for prolonging the aftereffects of cathodal tDCS , stimulation interval might be important Voluntarily modulating neural activity plays a key role in brain-computer interface ( BCI ) . In general , the self-regulated neural activation patterns are used in the current BCI systems involving the repetitive trainings with feedback for an attempt to achieve a high- quality control performance . With the limitation posed by the training procedure in most BCI studies , the present work aims to investigate whether directly modulating the neural activity by using an external method could facilitate the BCI control . We design ed an experimental paradigm that combines anodal transcranial direct current stimulation ( tDCS ) with a motor imagery (MI)-based feedback EEG BCI system . Thirty-two young and healthy human subjects were r and omly assigned to the real and sham stimulation groups to evaluate the effect of tDCS-induced EEG pattern changes on BCI classification accuracy . Results showed that the anodal tDCS obviously induces sensorimotor rhythm (SMR)-related event-related desynchronization ( ERD ) pattern changes in the upper-mu ( 10 - 14 Hz ) and beta ( 14 - 26 Hz ) rhythm components . Both the online and offline BCI classification results demonstrate that the enhancing ERD patterns could conditionally improve BCI performance . This pilot study suggests that the tDCS is a promising method to help the users to develop reliable BCI control strategy in a relatively short time PURPOSE Transcranial direct current stimulation ( tDCS ) has proven to be a useful tool for fundamental brain research as well as for attempts in therapy of neurological and psychiatric diseases by modulating neuronal plasticity . Little is understood about the effects of tDCS are influenced by hemispheric dominance , even less in terms of h and edness . The aim of our pilot study was to investigate whether tDCS induced neuroplastic changes may be different in right- and left-h and ed individuals due to existing differences in hemispheric lateralisation . METHODS We measured changes in motor evoked potentials ( MEPs ) after application of tDCS in 8 right-h and ers , 8 left-h and ers and 8 mixed-h and ers according to the Edinburgh H and edness Inventory ( EHI ) . In double-blind sessions , we applied either anodal or cathodal tDCS for 5 minutes for each hemisphere . RESULTS While motor thresholds ( MT ) seem to be not influenced by h and edness significantly , in right-h and ed subjects we reproduced the well-known effects of tDCS : anodal stimulation increased while cathodal stimulation decreased MEP amplitudes . However , left- and mixed-h and ed subjects differed from right-h and ed subjects . After anodal stimulation of the left hemisphere the increase of the MEP amplitudes was stronger in right h and ed subjects than in left and mixed h and ed subjects . Interestingly , after cathodal stimulation of the left hemisphere this difference was less marked . The stimulation of the right hemisphere showed the same tendency , but results were not significant . CONCLUSIONS For the first time , we are able to demonstrate that the modulating effects of tDCS on corticospinal excitability differ moderately in the left- and mixed-h and ed population compared to right-h and ed subjects . The shown differences according to h and edness should be taken into account in further studies Low-level direct currents ( DC ) are thought to polarize brain tissue and to affect brain processes . The present experiments investigated the effects of low-level transcortical DC-currents on response speed and physiological variables in humans . The DC-currents were applied during the warning interval within a constant foreperiod reaction time paradigm . Currents of less than 0.3 mA were applied between a vertex electrode and a noncephalic reference . The polarity of the electrical source varied r and omly across trials within subjects . The first two studies showed that subjects respond fastest when the positive pole is applied to the vertex . Under the same conditions higher skin conductance responses were observed as compared to vertex negative conditions . The dynamics of the observed responses suggest that the brain " learns " to respond differentially to the different current polarities . This was confirmed by the third study , which documented different conditioned electroencephalic responses subsequent to current application Transcranial direct current stimulation ( tDCS ) over the primary motor cortex ( M1 ) has been shown to induce changes in motor performance and learning . Recent studies indicate that tDCS is capable of modulating widespread neural network properties within the brain . However the temporal evolution of online- and after-effects of tDCS on functional connectivity ( FC ) within and across the stimulated motor cortices ( M1 ) still remain elusive . In the present study , two different tDCS setups were investigated : ( i ) unilateral M1 tDCS ( anode over right M1 , cathode over the contralateral supraorbital region ) and ( ii ) bilateral M1 tDCS ( anode over right M1 , cathode over left M1 ) . In a r and omized single-blinded cross-over design , 12 healthy subjects underwent functional magnetic resonance imaging at rest before , during and after 20 min of either bi- , unilateral , or sham M1 tDCS . Seed-based FC analysis was used to investigate tDCS-induced changes across and within M1 . We found that bilateral M1 tDCS induced ( a ) a decrease in interhemispheric FC during stimulation and ( b ) an increase in intracortical FC within right M1 after termination of the intervention . While unilateral M1 tDCS also result ed in similar effects during stimulation , no such changes could be observed after termination of tDCS . Our results provide evidence that depending on the electrode montage , tDCS acts upon a modulation of either intracortical and /or interhemispheric processing of M1 In recent years , two techniques have become available for the non-invasive stimulation of human motor cortex : transcranial magnetic stimulation ( TMS ) and transcranial direct current stimulation ( tDCS ) . The effects of TMS and tDCS when applied over motor cortex should be considered with regard not only to cortical circuits but also to spinal motor circuits . The different modes of action and specificity of TMS and tDCS suggest that their effects on spinal network excitability may be different from that in the cortex . Until now , the effects of tDCS on lumbar spinal network excitability have never been studied . In this series of experiments , on healthy subjects , we studied the effects of anodal tDCS over the lower limb motor cortex on ( i ) reciprocal Ia inhibition projecting from the tibialis anterior muscle ( TA ) to the soleus ( SOL ) , ( ii ) presynaptic inhibition of SOL Ia terminals , ( iii ) homonymous SOL recurrent inhibition , and ( iv ) SOL H-reflex recruitment curves . The results show that anodal tDCS decreases reciprocal Ia inhibition , increases recurrent inhibition and induces no modification of presynaptic inhibition of SOL Ia terminals and of SOL-H reflex recruitment curves . Our results indicate therefore that the effects of tDCS are the opposite of those previously described for TMS on spinal network excitability . They also indicate that anodal tDCS induces effects on spinal network excitability similar to those observed during co-contraction suggesting that anodal tDCS activates descending corticospinal projections mainly involved in co-contractions Transcranial direct current stimulation ( tDCS ) and transcranial r and om noise stimulation ( tRNS ) consist in the application of electrical current of small intensity through the scalp , able to modulate perceptual and motor learning , probably by changing brain excitability . We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning , as well as associated brain activity changes using functional magnetic resonance imaging ( fMRI ) . We applied anodal and cathodal tDCS , low-frequency and high-frequency tRNS ( lf-tRNS , 0.1–100 Hz ; hf-tRNS 101–640 Hz , respectively ) and sham stimulation over the primary motor cortex ( M1 ) during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased . Functional imaging scans were acquired throughout the whole experiment . Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation , an effect that remained for 20 minutes after cessation of stimulation in the late learning phase . Motor learning-related activity decreased in several regions as reported previously , however , there was no significant modulation of brain activity by tDCS . In opposition to this , hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous , probably due to interaction with ongoing neuronal oscillations . This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods OBJECTIVES We attempted to evaluate whether cortical activation result ing from h and movements is changed by transcranial direct current stimulation ( tDCS ) applied on the primary motor cortex for the h and in the human brain , using functional MRI ( fMRI ) . METHODS Fourteen normal subjects were recruited ; subjects were r and omly assigned to either the tDCS group ( n=7 ) or the sham group ( n=7 ) . fMRI was performed with h and grasp-release movements at 1Hz before and after 20 min of intervention ( the tDCS group : anodal tDCS , the sham group : sham stimulation ) . RESULTS The activation of the tDCS underlying primary sensorimotor cortex ( SM1 ) was significantly increased in the tDCS group ( p<0.05 ) . By contrast , the SM1 was significantly decreased in the sham group in terms of the voxel count and intensity ( p<0.05 ) . No subjects complained of any adverse symptoms or signs . CONCLUSION We demonstrated that anodal tDCS increased the cortical excitability of the underlying motor cortex in the human brain . It seems that tDCS is an effective modality to modulate brain function Cholinergic neuromodulation is pivotal for arousal , attention , and cognitive processes . Loss or dysregulation of cholinergic inputs leads to cognitive impairments like those manifested in Alzheimer 's disease . Such dysfunction can be at least partially restored by an increase of acetylcholine ( ACh ) . In animal studies , ACh selectively facilitates long-term excitability changes induced by feed-forward afferent input . Consequently , it has been hypothesized that ACh enhances the signal-to-noise ratio of input processing . However , the neurophysiological foundation for its ability to enhance cognition in humans is not well documented . In this study we explore the effects of rivastigmine , a cholinesterase inhibitor , on global and synapse-specific forms of cortical plasticity induced by transcranial direct current stimulation ( tDCS ) and paired associative stimulation ( PAS ) on 10–12 healthy subjects , respectively . Rivastigmine essentially blocked the induction of the global excitability enhancement elicited by anodal tDCS and revealed a tendency to first reduce and then stabilize cathodal tDCS-induced inhibitory aftereffects . However , ACh enhanced the synapse-specific excitability enhancement produced by facilitatory PAS and consoli date d the inhibitory PAS-induced excitability diminution . These findings are in line with a cholinergic focusing effect that optimizes the detection of relevant signals during information processing in humans Transcranial direct current stimulation ( tDCS ) of the primary motor h and area ( M1 ) can produce lasting polarity-specific effects on corticospinal excitability and motor learning in humans . In 16 healthy volunteers , O positron emission tomography ( PET ) of regional cerebral blood flow ( rCBF ) at rest and during finger movements was used to map lasting changes in regional synaptic activity following 10 min of tDCS ( + /-1 mA ) . Bipolar tDCS was given through electrodes placed over the left M1 and right frontopolar cortex . Eight subjects received anodal or cathodal tDCS of the left M1 , respectively . When compared to sham tDCS , anodal and cathodal tDCS induced widespread increases and decreases in rCBF in cortical and subcortical areas . These changes in rCBF were of the same magnitude as task-related rCBF changes during finger movements and remained stable throughout the 50-min period of PET scanning . Relative increases in rCBF after real tDCS compared to sham tDCS were found in the left M1 , right frontal pole , right primary sensorimotor cortex and posterior brain regions irrespective of polarity . With the exception of some posterior and ventral areas , anodal tDCS increased rCBF in many cortical and subcortical regions compared to cathodal tDCS . Only the left dorsal premotor cortex demonstrated an increase in movement related activity after cathodal tDCS , however , modest compared with the relatively strong movement-independent effects of tDCS . Otherwise , movement related activity was unaffected by tDCS . Our results indicate that tDCS is an effective means of provoking sustained and widespread changes in regional neuronal activity . The extensive spatial and temporal effects of tDCS need to be taken into account when tDCS is used to modify brain function Transcranial direct current stimulation ( tDCS ) is a noninvasive technique that modulates the excitability of neurons within the motor cortex ( M1 ) . Although the aftereffects of anodal tDCS on modulating cortical excitability have been described , there is limited data describing the outcomes of different tDCS intensities on intracortical circuits . To further eluci date the mechanisms underlying the aftereffects of M1 excitability following anodal tDCS , we used transcranial magnetic stimulation ( TMS ) to examine the effect of different intensities on cortical excitability and short-interval intracortical inhibition ( SICI ) . Using a r and omized , counterbalanced , crossover design , with a one-week wash-out period , 14 participants ( 6 females and 8 males , 22–45 years ) were exposed to 10 minutes of anodal tDCS at 0.8 , 1.0 , and 1.2 mA. TMS was used to measure M1 excitability and SICI of the contralateral wrist extensor muscle at baseline , immediately after and 15 and 30 minutes following cessation of anodal tDCS . Cortical excitability increased , whilst SICI was reduced at all time points following anodal tDCS . Interestingly , there were no differences between the three intensities of anodal tDCS on modulating cortical excitability or SICI . These results suggest that the aftereffect of anodal tDCS on facilitating cortical excitability is due to the modulation of synaptic mechanisms associated with long-term potentiation and is not influenced by different tDCS intensities Transcranial direct current stimulation ( tDCS ) is a noninvasive brain stimulation technique that induces changes in cortical excitability : anodal stimulation increases while cathodal stimulation reduces excitability . Imaging studies performed after unilateral stimulation have shown conflicting results regarding the effects of tDCS on surrogate markers of neuronal activity . The aim of this study was to directly measure these effects on activation-induced changes in regional cerebral blood flow ( ⊿rBF ) using positron emission tomography ( PET ) during bilateral tDCS . Nine healthy subjects underwent repeated rCBF measurements with 15O-water and PET during a simple motor task while receiving tDCS or sham stimulation over the primary motor cortex ( M1 ) . Motor evoked potentials ( MEPs ) were also assessed before and after real and sham stimulation . During tDCS with active movement , ⊿rBF in M1 was significantly lower on the cathodal than the anodal side when compared with sham stimulation . This decrease in ⊿rBF was accompanied by a decrease in MEP amplitude on the cathodal side . No effect was observed on resting or activated rCBF relative to sham stimulation . We thus conclude that it is the interaction of cathodal tDCS with activation-induced ⊿rBF rather than the effect on resting or activated rCBF itself which constitutes the physiological imaging correlate of tDCS UNLABELLED Fibromyalgia is a prevalent chronic pain syndrome characterized by altered pain and sensory processing in the central nervous system , which is often refractory to multiple therapeutic approaches . Given previous evidence supporting analgesic properties of noninvasive brain stimulation techniques in this condition , this study examined the effects of a novel , more focal method of transcranial direct current stimulation ( tDCS ) , using the 4 × 1-ring configuration of high-definition (HD)-tDCS , on overall perceived pain in fibromyalgia patients . In this patient- and assessor-blind , sham-controlled , crossover trial , 18 patients were r and omized to undergo single 20-minute sessions of anodal , cathodal , and sham HD-tDCS at 2.0 mA in a counterbalanced fashion . The center electrode was positioned over the left primary motor cortex . Pain scales and sensory testing were assessed before and after each intervention . A finite element method brain model was generated to predict electric field distribution . We found that both active stimulation conditions led to significant reduction in overall perceived pain as compared to sham . This effect occurred immediately after cathodal HD-tDCS and was evident for both anodal and cathodal HD-tDCS 30 minutes after stimulation . Furthermore , active anodal stimulation induced a significant bilateral increase in mechanical detection thresholds . These interventions proved well tolerated in our patient population . PERSPECTIVE 4 × 1-ring HD-tDCS , a novel noninvasive brain stimulation technique capable of more focal and targeted stimulation , provides significant reduction in overall perceived pain in fibromyalgia patients as compared to sham stimulation , irrespective of current polarity . This technique may have other applications in research and clinical setting s , which should be further explored Background Premotor cortical regions ( PMC ) play an important role in the orchestration of motor function , yet their role in compensatory mechanisms in a disturbed motor system is largely unclear . Previous studies are consistent in describing pronounced anatomical and functional connectivity between the PMC and the primary motor cortex ( M1 ) . Lesion studies consistently show compensatory adaptive changes in PMC neural activity following an M1 lesion . Non-invasive brain modification of PMC neural activity has shown compensatory neurophysiological aftereffects in M1 . These studies have contributed to our underst and ing of how M1 responds to changes in PMC neural activity . Yet , the way in which the PMC responds to artificial inhibition of M1 neural activity is unclear . Here we investigate the neurophysiological consequences in the PMC and the behavioral consequences for motor performance of stimulation mediated M1 inhibition by cathodal transcranial direct current stimulation ( tDCS ) . Purpose The primary goal was to determine how electrophysiological measures of PMC excitability change in order to compensate for inhibited M1 neural excitability and attenuated motor performance . Hypothesis Cathodal inhibition of M1 excitability leads to a compensatory increase of ipsilateral PMC excitability . Methods We enrolled 16 healthy participants in this r and omized , double-blind , sham-controlled , crossover design study . All participants underwent navigated transcranial magnetic stimulation ( nTMS ) to identify PMC and M1 corticospinal projections as well as to evaluate electrophysiological measures of cortical , intracortical and interhemispheric excitability . Cortical M1 excitability was inhibited using cathodal tDCS . Finger-tapping speeds were used to examine motor function . Results Cathodal tDCS successfully reduced M1 excitability and motor performance speed . PMC excitability was increased for longer and was the only significant predictor of motor performance . Conclusion The PMC compensates for attenuated M1 excitability and contributes to motor performance maintenance The accurate identification of obscured and concealed objects in complex environments was an important skill required for survival during human evolution , and is required today for many forms of expertise . Here we used transcranial direct current stimulation ( tDCS ) guided using neuroimaging to increase learning rate in a novel , minimally guided discovery-learning paradigm . Ninety-six subjects identified threat-related objects concealed in naturalistic virtual surroundings used in real-world training . A variety of brain networks were found using functional magnetic resonance imaging ( fMRI ) data collected at different stages of learning , with two of these networks focused in right inferior frontal and right parietal cortex . Anodal 2.0 mA tDCS performed for 30 min over these regions in a series of single-blind , r and omized studies result ed in significant improvements in learning and performance compared with 0.1 mA tDCS . This difference in performance increased to a factor of two after a one-hour delay . A dose-response effect of current strength on learning was also found . Taken together , these brain imaging and stimulation studies suggest that right frontal and parietal cortex are involved in learning to identify concealed objects in naturalistic surroundings . Furthermore , they suggest that the application of anodal tDCS over these regions can greatly increase learning , result ing in one of the largest effects on learning yet reported . The methods developed here may be useful to decrease the time required to attain expertise in a variety of setting Background The mu event-related desynchronization ( ERD ) is supposed to reflect motor preparation and appear during motor imagery . The aim of this study is to examine the modulation of ERD with transcranial direct current stimulation ( tDCS ) . Methods Six healthy subjects were asked to imagine their right h and grasping something after receiving a visual cue . Electroencephalograms ( EEGs ) were recorded near the left M1 . ERD of the mu rhythm ( mu ERD ) by right h and motor imagery was measured . tDCS ( 10 min , 1 mA ) was used to modulate the cortical excitability of M1 . Anodal , cathodal , and sham tDCS were tested in each subject with a r and omized sequence on different days . Each condition was separated from the preceding one by more than 1 week in the same subject . Before and after tDCS , mu ERD was assessed . The motor thresholds ( MT ) of the left M1 were also measured with transcranial magnetic stimulation . Results Mu ERD significantly increased after anodal stimulation , whereas it significantly decreased after cathodal stimulation . There was a significant correlation between mu ERD and MT . Conclusions Opposing effects on mu ERD based on the orientation of the stimulation suggest that mu ERD is affected by cortical excitability Transcranial direct current stimulation ( tDCS ) has been proposed for experimental and therapeutic modulation of regional brain function . Specifically , anodal tDCS of the dorsolateral prefrontal cortex ( DLPFC ) together with cathodal tDCS of the supraorbital region have been associated with improvement of cognition and mood , and have been suggested for the treatment of several neurological and psychiatric disorders . Although modeled mathematically , the distribution , direction , and extent of tDCS-mediated effects on brain physiology are not well understood . The current study investigates whether tDCS of the human prefrontal cortex modulates resting-state network ( RSN ) connectivity measured by functional magnetic resonance imaging ( fMRI ) . Thirteen healthy subjects underwent real and sham tDCS in r and om order on separate days . tDCS was applied for 20 min at 2 mA with the anode positioned over the left DLPFC and the cathode over the right supraorbital region . Patterns of resting-state brain connectivity were assessed before and after tDCS with 3 T fMRI , and changes were analyzed for relevant networks related to the stimulation – electrode localizations . At baseline , four RSNs were detected , corresponding to the default mode network ( DMN ) , the left and right frontal-parietal networks ( FPNs ) and the self-referential network . After real tDCS and compared with sham tDCS , significant changes of regional brain connectivity were found for the DMN and the FPNs both close to the primary stimulation site and in connected brain regions . These findings show that prefrontal tDCS modulates resting-state functional connectivity in distinct functional networks of the human brain Interest in transcranial direct current stimulation ( tDCS ) as a new tool in neuropsychiatry has led to the need to establish optimal treatment protocol s. In an intra-individual r and omized cross-over design , 11 healthy volunteers received five tDCS sessions to the left primary motor cortex on consecutive weekdays at a constant or gradually increasing current intensity , in two separate weeks of testing . Cortical excitability was assessed before and after tDCS at each session through peripheral electromyographic recordings of motor-evoked potentials . Both conditions led to significant cumulative increases in cortical excitability across the week but there were no significant differences between the two groups . Motor thresholds decreased significantly from Monday to Friday in both conditions . This study demonstrated that , in the motor cortex , administration of tDCS five times per week whether at a constant intensity or at a gradually increasing intensity was equally effective in increasing cortical excitability The aim of this study was to test and compare the effects of a within-subject design of repetitive transcranial magnetic stimulation ( rTMS ) [ coupled with sham transcranial direct current stimulation ( tDCS ) ] and tDCS ( coupled with sham rTMS ) on the motor cortex excitability and also compare the results against sham tDCS/sham rTMS . We conducted a double-blinded , r and omized , sham-controlled , cross-over trial . Eleven right-h and ed , healthy individuals ( five women , mean age : 39.8 years , SD 13.4 ) received the three interventions ( cross-over design ) in a r and omized order : ( a ) high-frequency ( HF ) rTMS ( + sham tDCS ) , ( b ) anodal tDCS ( + sham rTMS ) , and ( c ) sham stimulation ( sham rTMS+sham tDCS ) . Cortical excitability measurements [ motor threshold , motor evoked potential ( MEP ) , intracortical facilitation and inhibition , and transcallosal inhibition ] and motor behavioral assessment s were used as outcome measures . Between-group analysis of variance showed that MEP amplitude after HF rTMS was significantly higher than MEP amplitude after anodal tDCS ( P=0.001 ) . Post-hoc analysis showed a significant increase in MEP amplitude after HF rTMS ( 25.3 % , P=0.036 ) and a significant decrease in MEP amplitude after anodal tDCS ( −32.7 % , P=0.001 ) . There was a similar increase in motor function as indexed by Jebsen – Taylor H and Function Test in the two active groups compared with sham stimulation . In conclusion , here , we showed that although both techniques induced similar motor gains , they induce opposing results in cortical excitability . HF rTMS is associated with an increase in corticospinal excitability , whereas 20 min of tDCS induces the opposite effect . We discuss potential implication s of these results to future clinical experiments using rTMS or tDCS for motor function enhancement Background Many double-blind clinical trials of transcranial direct current stimulation ( tDCS ) use stimulus intensities of 2 mA despite the fact that blinding has not been formally vali date d under these conditions . The aim of this study was to test the assumption that sham 2 mA tDCS achieves effective blinding . Methods A r and omised double blind crossover trial . 100 tDCS-naïve healthy volunteers were incorrectly advised that they there were taking part in a trial of tDCS on word memory . Participants attended for two separate sessions . In each session , they completed a word memory task , then received active or sham tDCS ( order r and omised ) at 2 mA stimulation intensity for 20 minutes and then repeated the word memory task . They then judged whether they believed they had received active stimulation and rated their confidence in that judgement . The blinded assessor noted when red marks were observed at the electrode sites post-stimulation . Results tDCS at 2 mA was not effectively blinded . That is , participants correctly judged the stimulation condition greater than would be expected to by chance at both the first session ( kappa level of agreement ( κ ) 0.28 , 95 % confidence interval ( CI ) 0.09 to 0.47 p = 0.005 ) and the second session ( κ = 0.77 , 95%CI 0.64 to 0.90 ) , p = < 0.001 ) indicating inadequate participant blinding . Redness at the reference electrode site was noticeable following active stimulation more than sham stimulation ( session one , κ = 0.512 , 95%CI 0.363 to 0.66 , p<0.001 ; session two , κ = 0.677 , 95%CI 0.534 to 0.82 ) indicating inadequate assessor blinding . Conclusions Our results suggest that blinding in studies using tDCS at intensities of 2 mA is inadequate . Positive results from such studies should be interpreted with caution Weak transcranial DC stimulation ( tDCS ) of the human motor cortex results in excitability shifts during and after the end of stimulation , which are most probably localized intracortically . Anodal stimulation enhances excitability , whereas cathodal stimulation reduces it . Although the after-effects of tDCS are NMDA receptor-dependent , nothing is known about the involvement of additional receptors . Here we show that pharmacological strengthening of GABAergic inhibition modulates selectively the after-effects elicited by anodal tDCS . Administration of the GABA(A ) receptor agonist lorazepam result ed in a delayed , but then enhanced and prolonged anodal tDCS-induced excitability elevation . The initial absence of an excitability enhancement under lorazepam is most probably caused by a loss of the anodal tDCS-generated intracortical diminution of inhibition and enhancement of facilitation , which occurs without pharmacological intervention . The reasons for the late-occurring excitability enhancement remain unclear . Because intracortical inhibition and facilitation are not changed in this phase compared with pre-tDCS values , excitability changes originating from remote cortical or subcortical areas could be involved We studied the effect of stimulus intensity , coil size , mental alertness and prestimulus muscle contraction on the variability of motor evoked potentials ( MEPs ) produced by magnetic cortical stimulation ( MCS ) . In 5 healthy subjects we delivered MCS either with a circular coil centered at the vertex or a figure-8 coil centered over the motor cortex h and area , recording from first dorsal interosseous . With the subject at rest or exerting 5 % maximum voluntary contraction , 30 consecutive stimuli were given at 4 stimulus intensities ( SIs ) in 10 % increments above resting motor threshold . Concurrent mental arithmetic constituted mental alertness . Spectral analysis was performed on data from 300 consecutive stimuli . The variability of MEP response size was inversely related to stimulus intensity , prestimulus voluntary muscle contraction , the recruitment of motoneurons and the size of the field generated by the magnetic coil . The MEP variability was larger than and not correlated with the variability of the H-reflex . Fast Fourier transformation and cross-correlation analysis did not identify a consistent dominant frequency , suggesting that the variability in MEP size is essentially r and om . We suggest that the variability in MEP response is caused by constant , rapid , spontaneous fluctuations in corticospinal and segmental motoneuron excitability levels . Any maneuver that raises this level or increases the probability of motoneuron firing will decrease MEP variability Since about 15 years , transcranial magnetic stimulation ( TMS ) is used as a technique to investigate the function of specific cortical regions . Single pulse TMS studies have targeted the dorsolateral premotor cortex ( dlPMC ) to characterize premotor-motor interactions in movement disorders . Repetitive TMS ( rTMS ) trials have targeted the dorsolateral prefrontal cortex ( dlPFC ) to treat depression . In almost all previous studies , these targets have been defined according to a " st and ard " scalp distance to the site of stimulation evoking motor responses of maximal amplitude in the contralateral h and ( " h and motor hotspot " corresponding to the primary motor cortex , M1 ) . The " st and ard " procedure of coil positioning locates the dlPMC and dlPFC as 2 - 3 and 5 cm , respectively , anterior to the " h and motor hotspot " . The aim of our study was to compare the locations of M1 , dlPMC and dlPFC targets provided by the " st and ard " procedure of coil positioning and those provided by using a neuronavigation system integrating individual brain magnetic resonance imaging ( MRI ) . Twenty-two patients were enrolled , all being treated for depressive symptoms in the context of chronic pain syndrome . The centers of the dlPMC and dlPFC regions were accurately targeted by the " st and ard " procedure in 14 and eight patients ( 64 and 36 % of the series ) , respectively . In the other patients , the " st and ard " procedure located the dlPMC target on the M1/dlPMC border and the dlPFC target on the dlPMC/dlPFC border . On average , the MRI-guided location of M1 , dlPMC , and dlPFC was , respectively , 6.1 mm posterior , 31.7 mm anterior and 69.0 mm anterior to the " h and motor hotspot " . The " st and ard " procedure failed to accurately locate the dlPMC and dlPFC targets by about 1 and 2 cm , respectively . A statistical analysis of the MRI coordinates ( x , y , z ) of the targets revealed that the M1 target was more posterior , the dlPMC target more superficial and the dlPFC target more anterior , lateral , and deeper , using neuronavigation compared to the " st and ard " procedure . This study confirms that the " st and ard " procedure of coil positioning is not accurate to target a desired cortical region . Target location can be improved by the use of a navigation system taking individual brain anatomy into account . The present results incline to be cautious on the pathophysiological interpretations of previous results reported in TMS studies based on " st and ard " targeting , e.g. regarding premotor-motor interactions . Similarly , the inaccuracy of the " st and ard " procedure of coil positioning could partly explain the between- study variability of the therapeutic effects produced by rTMS in patients with depression . Our results strongly support a more anterior and lateral placement of the TMS coil for dlPFC stimulation in the treatment of depression BACKGROUND Evidence from recent clinical trials suggests that transcranial direct current stimulation ( tDCS ) may have potential in treating neuropsychiatric disorders . However , the optimal frequency at which tDCS sessions should be administered is unknown . OBJECTIVE /HYPOTHESIS This study investigated the effects of daily or second daily tDCS sessions on motor cortical excitability , over a 5-day period . METHODS Twelve healthy volunteers received daily or second daily sessions of tDCS to the left primary motor cortex over the study period , in a r and omized , intraindividual crossover design . Motor cortical excitability was assessed before and after tDCS at each session through responses to transcranial magnetic stimulation . RESULTS Over a fixed 5-day period , tDCS induced greater increases in MEP amplitude when given daily rather than second daily . Analyses showed that this difference reflected greater cumulative effects between sessions rather than a greater response to each individual tDCS session . CONCLUSIONS These results demonstrate that in the motor cortex of healthy volunteers , tDCS alters cortical excitability more effectively when given daily rather than second daily over a 5-day period Although cathodal transcranial direct current stimulation ( tDCS ) decreases cortical excitability , the mechanisms underlying DC-induced changes remain largely unclear . In this study we investigated the effect of cathodal DC stimulation on spontaneous neural activity and on motor responses evoked by stimulation of the central and peripheral nervous system . We studied 17 healthy volunteers . Transcranial magnetic stimulation ( TMS ) and transcranial electrical stimulation ( TES ) of the motor area were used to study the effects of cathodal tDCS ( 1.5 mA , 10 min ) on resting motor threshold and motor evoked potentials ( MEPs ) recorded from the contralateral first dorsal interosseous muscle ( FDI ) . The electroencephalographic ( EEG ) activity in response to cathodal tDCS was analysed by power spectral density ( PSD ) . Motor axonal excitability changes in response to transcutaneous DC stimulation of the ulnar nerve ( 0.3 mA , 10 min ) were assessed by testing changes in the size of the compound muscle action potential ( CMAP ) elicited by submaximal nerve stimulation . Cathodal tDCS over the motor area for 10 min increased the motor threshold and decreased the size of MEPs evoked by TMS for at least 60 min after current offset ( t(0 ) 71.7 + /- 5 % , t(20 ) 50.8 + /- 11 % , t(40 ) 47.7 + /- 7.7 % , and t(60 ) 39.7 + /- 6.4 % , P < 0.01 ) . The tDCS also significantly decreased the size of MEPs elicited by TES ( t(0 ) 64 + /- 16.4 % , P = 0.09 ; t(20 ) 67.6 + /- 10.8 % , P = 0.06 ; and t(40 ) 58.3 + /- 9.9 % , P < 0.05 ) . At the same time in the EEG the power of delta ( 2 - 4 Hz ) and theta ( 4 - 7 Hz ) rhythms increased ( delta 181.1 + /- 40.2 , P < 0.05 ; and theta 138.7 + /- 27.6 , P = 0.07 ) . At the peripheral level cathodal DC stimulation increased the size of the ulnar nerve CMAP ( 175 + /- 34.3 % , P < 0.05 ) . Our findings demonstrate that the after-effects of tDCS have a non-synaptic mechanism of action based upon changes in neural membrane function . These changes apart from reflecting local changes in ionic concentrations , could arise from alterations in transmembrane proteins and from electrolysis-related changes in [ H(+ ) ] induced by exposure to constant electric field 1 . Changes in excitability of the motor cortex induced by a transcranial magnetic stimulation ( TMS ) were examined by simultaneous recording of the evoked corticospinal volley and the compound surface electromyographic ( EMG ) response in the biceps brachii following paired-pulse TMS in five conscious subjects . The effects of a varying interstimulus interval ( ISI ) and a conditioning stimulus intensity were also investigated . 2 . A submotor threshold conditioning stimulus inhibited the test responses at ISIs of 2 - 5 ms . A supramotor threshold conditioning stimulus inhibited the test responses at ISIs of 100 - 200 ms . Both of these inhibitions were prominent in late I waves . 3 . There was a facilitation of the test responses at an ISI of 25 ms that was prominent in late I waves . The facilitation evoked by the supramotor threshold conditioning stimulus was more prominent than that evoked by the submotor threshold conditioning stimulus . 4 . It is concluded that single TMS induced the triphasic changes of the motor cortex excitability in conscious humans that result ed in changes in EMG responses following paired TMS In this paper we demonstrate in the intact human the possibility of a non-invasive modulation of motor cortex excitability by the application of weak direct current through the scalp . Excitability changes of up to 40 % , revealed by transcranial magnetic stimulation , were accomplished and lasted for several minutes after the end of current stimulation . Excitation could be achieved selectively by anodal stimulation , and inhibition by cathodal stimulation . By varying the current intensity and duration , the strength and duration of the after-effects could be controlled . The effects were probably induced by modification of membrane polarisation . Functional alterations related to post-tetanic potentiation , short-term potentiation and processes similar to postexcitatory central inhibition are the likely c and i date s for the excitability changes after the end of stimulation . Transcranial electrical stimulation using weak current may thus be a promising tool to modulate cerebral excitability in a non-invasive , painless , reversible , selective and focal way Brain content of myoinositol ( mI ) has been shown to be altered in several neuropsychiatric conditions . Likewise , various forms of electric currents have been applied to the human brain for therapeutic purpose s in neuropsychiatric diseases . In this study we aim ed to depict the effects of low-power transcranial direct current stimulation ( tDCS ) on brain mI by proton magnetic resonance spectroscopy ( (1)H-MRS ) . We studied two groups of five healthy subjects by (1)H-MRS : the first group was studied before and after both anodal and sham ( placebo ) tDCS over the right frontal lobe , and the second group was studied at the same intervals without undergoing either sham or anodal tDCS . Anodal tDCS induced a significant increase of mI content at 30 min after stimulation offset ( 141.5 + /- 16.7 % , P < 0.001 ) below the stimulating electrode but not in distant regions , such as the visual cortex , whereas sham tDCS failed to induce changes in mI. Neither N-acetyl-aspartate ( NAA ) nor the other metabolite contents changed after anodal or sham stimulation . (1)H-MRS represents a powerful tool to follow the regional effects of tDCS on brain mI and , possibly , on the related phosphoinositide system Transcranial direct current stimulation ( tDCS ) of the human motor cortex at an intensity of 1 mA with an electrode size of 35 cm(2 ) has been shown to induce shifts of cortical excitability during and after stimulation . These shifts are polarity-specific with cathodal tDCS result ing in a decrease and anodal stimulation in an increase of cortical excitability . In clinical and cognitive studies , stronger stimulation intensities are used frequently , but their physiological effects on cortical excitability have not yet been explored . Therefore , here we aim ed to explore the effects of 2 mA tDCS on cortical excitability . We applied 2 mA anodal or cathodal tDCS for 20 min on the left primary motor cortex of 14 healthy subjects . Cathodal tDCS at 1 mA and sham tDCS for 20 min was administered as control session in nine and eight healthy subjects , respectively . Motor cortical excitability was monitored by transcranial magnetic stimulation (TMS)-elicited motor-evoked potentials ( MEPs ) from the right first dorsal interosseous muscle . Global corticospinal excitability was explored via single TMS pulse-elicited MEP amplitudes , and motor thresholds . Intracortical effects of stimulation were obtained by cortical silent period ( CSP ) , short latency intracortical inhibition ( SICI ) and facilitation ( ICF ) , and I wave facilitation . The above-mentioned protocol s were recorded both before and immediately after tDCS in r and omized order . Additionally , single-pulse MEPs , motor thresholds , SICI and ICF were recorded every 30 min up to 2 h after stimulation end , evening of the same day , next morning , next noon and next evening . Anodal as well as cathodal tDCS at 2 mA result ed in a significant increase of MEP amplitudes , whereas 1 mA cathodal tDCS decreased corticospinal excitability . A significant shift of SICI and ICF towards excitability enhancement after both 2 mA cathodal and anodal tDCS was observed . At 1 mA , cathodal tDCS reduced single-pulse TMS-elicited MEP amplitudes and shifted SICI and ICF towards inhibition . No significant changes were observed in the other protocol s. Sham tDCS did not induce significant MEP alterations . These results suggest that an enhancement of tDCS intensity does not necessarily increase efficacy of stimulation , but might also shift the direction of excitability alterations . This should be taken into account for applications of the stimulation technique using different intensities and duration s in order to achieve stronger or longer lasting after-effects Transcranial direct current stimulation ( tDCS ) is a novel intervention that can modulate brain excitability in health and disease ; however , little is known about its effects on bilaterally innervated systems such as pharyngeal motor cortex . Here , we assess the effects of differing doses of tDCS on the physiology of healthy human pharyngeal motor cortex as a prelude to design ing a therapeutic intervention in dysphagic patients . Healthy subjects ( n = 17 ) underwent seven regimens of tDCS ( anodal 10 min 1 mA , cathodal 10 min 1 mA , anodal 10 min 1.5 mA , cathodal 10 min 1.5 mA , anodal 20 min 1 mA , cathodal 20 min 1 mA , Sham ) on separate days , in a double blind r and omized order . Bihemispheric motor evoked potential ( MEP ) responses to single-pulse transcranial magnetic stimulation ( TMS ) as well as intracortical facilitation ( ICF ) and inhibition ( ICI ) were recorded using a swallowed pharyngeal catheter before and up to 60 min following the tDCS . Compared with sham , both 10 min 1.5 mA and 20 min 1 mA anodal stimulation induced increases in cortical excitability in the stimulated hemisphere ( + 44 + /- 17 % and + 59 + /- 16 % , respectively ; P < 0.005 ) whereas only 10 min 1.5 mA cathodal stimulation induced inhibition ( -26 + /- 4 % , P = 0.02 ) . There were neither contralateral hemisphere changes nor any evidence for ICI or ICF in driving the ipsilateral effects . In conclusion , anodal tDCS can alter pharyngeal motor cortex excitability in an intensity-dependent manner , with little evidence for transcallosal spread . Anodal stimulation may therefore provide a useful means of stimulating pharyngeal cortex and promoting recovery in dysphagic patients |
12,851 | 28,926,388 | Conclusions : Direct HU measurement from diagnostic CT scans has the potential to be used opportunistically for osteoporosis screening , but in its current state it is not ready for clinical implementation . | Background : The purpose of this study was to determine the clinical opportunities for the use of computed tomography ( CT ) imaging for inferring bone quality and to critically analyze the correlation between dual x-ray absorptiometry ( DXA ) and diagnostic CT as reported in the literature . | Abstract Purpose Surgical options in the treatment of recurrent anterior shoulder instability are numerous . The Latarjet procedure is one of the most common procedures performed . It has been previously demonstrated that bone mineral density decreases with age . This reduction thus increases the risk of osteoporosis and osteoporosis-related iatrogenic , traumatic or pathological fractures . The objective of this study was to quantify the bone mineral density of the coracoid process in different age groups . The hypothesis was that mineral bone density of the coracoid process decreases with age . Methods Using the hospital ’s electronic data base , 60 patients who underwent a shoulder CT scan were r and omly selected retrospectively . Four groups of 15 were formed with mean ages of 20 , 30 , 40 and 50 years . Bone density , length , width and thickness of the coracoid process 10 mm from the tip were measured four times by two different evaluators . Bone density was expressed in Hounsfield units ( HU ) . Results The mean bone mineral density of the coracoid process significantly decreased with age ( p < 0.0001 ) . A lower but insignificant difference of bone mineral density was observed in females . A good inter- and intra-observer reliability was found for bone mineral density measurement of the coracoid process ( 0.67 and 0.7 , respectively ) . Conclusions The bone mineral density of the coracoid process diminishes with age , thus confirming our hypothesis . There is a good inter- and intra-observer reliability of our CT scan-based coracoid process bone mineral density measurement rendering it reproducible in daily clinical practice .Level of evidence IV Study Design . Retrospective case-control study . Objective . To determine the association of Hounsfield unit ( HU ) measurements with adjacent segment fractures after spinal fusion . Summary of Background Data . Adjacent segment fracture is a potentially devastating complication after spinal fusion surgery in osteoporotic patient . Recently , a technique for assessing bone mineral density using HU measurements from computed tomography was described and correlated with both dual-energy x-ray absorptiometry – assessed bone mineral density and compressive strength in an osseous model . Methods . Patients with adjacent segment fractures after spinal fusion were identified from a prospect ively collected patient data base and matched 1:1 with nonfracture controls on the basis of age , sex , and fusion construct . Minimum follow-up was 6 months . Patients with metabolic bone disease other than osteoporosis or those taking medications known to negatively alter bone strength were excluded . HU assessment was done according to the previously published protocol using the preoperative computed tomography . Results . Twenty patients had complete imaging data and could be matched to nonfracture controls . The groups were well matched with respect to age , sex , body mass index , and number of levels fused . Following the index surgical procedure , the fracture group had more positive sagittal balance than the control group ( 10.7 cm vs. 9.1 cm ) . Analysis of HU values at the fracture level showed a significantly lower value in the fracture group than in the controls ( 145.6 vs. 199.4 , P = 0.006 ) . Similarly , global assessment of HU across the thoracic and lumbar spines was significantly lower in the fracture group ( 139.9 vs. 170.1 , P = 0.032 ) . Conclusion . HU was significantly lower both locally and globally in the fracture cohort . Because computed tomographic scans are frequently part of preoperative planning for spinal fusion , this information should be incorporated in preoperative planning . Studies to prospect ively vali date HU as a predictor of adjacent segment fracture risk and to assess the effect of increasing HU preoperatively with medications for osteoporosis are needed . Level of Evidence : Background Iliosacral screw fixation has become a common method for surgical stabilization of acute disruptions of the pelvic ring . Placement of iliosacral screws into the first sacral ( S1 ) body is the preferred method of fixation , but size limitations and sacral dysmorphism may preclude S1 fixation . In these clinical situations , fixation into the second sacral ( S2 ) body has been recommended . The objective of this study was to evaluate the bone quality of the S1 compared to S2 in the described “ safe zone ” of iliosacral screw fixation in trauma patients . Material s and methods The pelvic computed tomography scans of 25 consecutive trauma patients , ages 18–49 , at a level 1 trauma center were prospect ively analyzed . Hounsfield units , a st and ardized computed tomography attenuation coefficient , was utilized to measure regional cancellous bone mineral density of the S1 and S2 . No change in the clinical protocol or treatment occurred as a consequence of inclusion in this study . Results A statically significant difference in bone quality was found when comparing the first and second sacral segment ( p = 0.0001 ) . Age , gender , or smoking status did not independently affect bone quality . Conclusion In relatively young , otherwise healthy trauma patients there is a statistically significant difference in the bone density of the first sacral segment compared to the second sacral segment . This study highlights the need for future biomechanical studies to investigate whether this difference is clinical ly relevant . Due to the relative osteopenia in the second sacral segment , which may impact the quality of fixation , we feel this technique should be used with caution .Level of evidence INTRODUCTION Patients with a fracture in the anterior pelvic ring often simultaneously demonstrate pain in the posterior pelvic ring . The aim of the present prospect i ve study was to assess the sensitivity of CT , MRI and clinical examination in the detection of fractures in the posterior pelvic ring in patients with fractures of the anterior pelvic ring diagnosed in conventional radiographs . METHODS Sixty patients with radiographic signs of an anterior pelvic ring injury were included in this prospect i ve analysis . Following a focused clinical examination of the posterior pelvis , all patients underwent both a CT and then a MRI scan of their pelvis . Two board certified radiologists evaluated the CT and MRI scans independently . To estimate the presence of osteoporosis the Hounsfield units of the vertebral body of L5 were measured in each case . RESULTS Fifty-three women and seven men , with a mean age of 74.7+/-15.6 years were included into the study . A fracture of the posterior pelvic ring was found in fourty-eight patients ( 80 % ) patients using MRI . Fractures of the posterior pelvic ring would have been missed in eight cases ( 17 % ) , if only CT had been used . Eighty-five percent of the patients with a posterior fracture had an osteoporosis . The majority of the cases suffered from a low energy trauma . Thirty-eight patients ( 83 % ) with positive clinical signs at the posterior pelvic ring actually had a fracture of the posterior pelvic ring in the MRI . The clinical examination proved to be equally effective to CT in detecting posterior pelvic ring fractures . CONCLUSION The significance of both , clinical examination and CT was confirmed in the detection of fractures in the posterior pelvic ring . MRI examination of the pelvis however , was found to be superior in detecting undislocated fractures in a cohort of patients with a high incidence of osteoporosis . Using MRI may be beneficial in select cases , especially when reduced bone density is suspected Abstract Objectives Further survival benefits may be gained from low-dose chest computed tomography ( CT ) by assessing vertebral fractures and bone density . We sought to assess the association between CT-measured vertebral fractures and bone density with all-cause mortality in lung cancer screening participants . Methods Following a case-cohort design , lung cancer screening trial participants ( N = 3,673 ) who died ( N = 196 ) during a median follow-up of 6 years ( inter-quartile range : 5.7–6.3 ) were identified and added to a r and om sample of N = 383 from the trial . We assessed vertebral fractures using Genant´s semiquantative method on sagittal reconstructions and measured bone density ( Hounsfield Units ( HU ) ) in vertebrae . Cox proportional hazards modelling was used to determine if vertebral fractures or bone density were independently predictive of mortality . Results The prevalence of vertebral fractures was 35 % ( 95 % confidence interval 30–40 % ) among survivors and 51 % ( 44–58 % ) amongst cases . After adjusting for age , gender , smoking status , pack years smoked , coronary and aortic calcium volume and pulmonary emphysema , the adjusted hazard ratio ( HR ) for vertebral fracture was 2.04 ( 1.43–2.92 ) . For each 10 HU decline in trabecular bone density , the adjusted HR was 1.08 ( 1.02–1.15 ) . Conclusions Vertebral fractures and bone density are independently associated with all-cause mortality . Key Points• Lung cancer screening chest computed tomography contains additional , potentially useful information . • Vertebral fractures and bone density are independently predictive of mortality . • This finding has implication s for screening and management decisions BACKGROUND CONTEXT The use of a novel lumbar pedicle cortical bone trajectory ( CBT ) screw has recently gained popularity , allowing for a minimally invasive approach and potentially improved screw purchase . However , to date , no studies have identified the ideal patient population to utilize this technology . PURPOSE This study reports the bone mineral density ( BMD ) using Hounsfield units ( HUs ) along a CBT screw pathway . Patients with a greater difference in density of bone in the lumbar vertebrae between the fixation points of the CBT and traditional pedicle screw may be optimal c and i date s to realize the advantages of this technique . STUDY DESIGN / SETTING A cross-sectional observational anatomic study was carried out . PATIENT SAMPLE The sample comprised 180 r and omly selected patients with lumbar computed tomography imaging from L1 to L5 spinal levels . OUTCOME MEASURES This study used computed tomography image-derived HUs as a metric for BMD . METHODS A total of 180 patients without previous lumbar surgery with computed tomography imaging of the lumbar spine met the inclusion criteria . Patients were chosen r and omly from an institutional data base based on age ( evenly distributed by decade of life ) and gender . Hounsfield units were measured at the expected end fixation point for both a cortical ( superior/posterior portion of the vertebral body ) and traditional pedicle trajectory ( mid-vertebral body ) . RESULTS Hounsfield unit values measured at the end fixation point for the CBT screw were significantly greater than that of the traditional pedicle screw in all age groups . The relative difference in HU values significantly increased with each decade of age ( p<.001 ) and caudal lumbar level ( p<.001 ) . In the osteoporotic group , as determined by well-established HU values , there was a significantly greater difference in the BMD of the CBT fixation point compared with the traditional trajectory ( p=.048-<.001 ) . CONCLUSIONS Bone mineral density as measured by HU values for the fixation point of the CBT screw is significantly greater than that of the traditional pedicle screw . This difference is even more pronounced when comparing osteoporotic and elderly patients to the general population . The data in this study suggest that the potential advantages from the CBT screw such as screw purchase may increase linearly with age and in osteoporotic patients Background : Double-bundle anterior cruciate ligament ( ACL ) reconstruction is a technically dem and ing procedure ; it requires drilling 2 tibial and 2 femoral tunnels . Tunnel communication , whether intraoperative or postoperative , is a serious complication : It jeopardizes knee stability and graft function . Hypothesis : During double-bundle ACL reconstruction , special aim ers would be helpful to avoid intraoperative bone bridge fracture . The bone bridge between the bone tunnels would maintain its structural integrity , and no tunnel communication would be observed postoperatively because of tunnel widening . Study design : Case series ; Level of evidence , 4 . Methods : This prospect i ve study included 32 patients undergoing double-bundle ACL reconstruction . A multidetector computed tomography study was performed at a mean of 17 months postoperatively . The thickness of the bone bridge between the bone tunnels was measured in the femoral and tibial sides on an axial and sagittal plane , respectively , at 3 locations : the level of the joint line , the midportion of the bone bridge , and the base of the bone bridge . The bone density of the bone bridge was measured in Hounsfield units in the same locations . Bone density of the anterior tibial cortex and lateral femoral condyle was measured for comparisons . Results : Tunnel communication occurred intraoperatively in 1 patient on the tibial side at the level of the joint line . In the rest of the patients , a well-defined triangular bone bridge was present between the 2 tunnels in the femoral and tibial sides . The thickness at the apex of the bone bridge was 2.0 and 2.2 mm for the femur and tibia , respectively . In addition , the density of the bone bridge at its apex was similar to that of cortical bone . Conclusion : This study demonstrated that double-bundle ACL reconstruction , as used with anatomic aim ers , produces a low rate of tunnel convergence . The bone bridge remains intact postoperatively , although it is thin at the level of the joint line BACKGROUND CONTEXT Spinous process fracture is a recognized complication associated with interspinous process spacer ( IPS ) surgery . Although occasionally identified by plain radiographs , computed tomography ( CT ) appears to identify a higher rate of such fractures . Although osteoporotic insufficiency fracture is considered a contraindication for IPS surgery , a formal risk factor analysis for this complication has not previously been reported . PURPOSE To identify risk factor(s ) associated with early spinous process fracture after IPS surgery . STUDY DESIGN / SETTING Prospect i ve cohort study of 39 consecutive patients with lumbar stenosis and neurogenic claudication undergoing IPS surgery at a single institution . METHODS Patients underwent preoperative dual-energy X-ray absorptiometry ( DXA ) scans , lumbar spine CT , and plain radiographs . Postoperatively , patients underwent repeat CT imaging within 6 months of surgery and serial radiographs at 2 weeks , 6 weeks , 3 months , 6 months , and 1 year . Preoperative CT scans were analyzed by calculating average Hounsfield units for a 1 cm(2 ) area of the midsagittal reconstructed image for four separate locations : midvertebral body , subcortical bone subjacent to the superior margin of the midspinous process , subcortical bone above the inferior margin of the midspinous process , and the midspinous process . RESULTS Thirty-eight patients underwent IPS surgery at a total of 50 levels ( 38 L4-L5 , 12 L3-L4 ; 26 one-level , 12 two-level ) . One patient underwent laminectomy at index surgery and was excluded from the analysis . Implants included 34 titanium X-STOP ( Medtronic , Memphis , TN , USA ) , 8 polyaryletheretherketone X-STOP ( Medtronic , Memphis , TN , USA ) , and 8 Aspen ( Lanx , Broomfield , CO , USA ) devices . Eleven spinous process fractures were identified by CT in 11 patients ( 22.0 % of levels ) . No fractures were apparent on plain radiographs . The rate of spondylolisthesis observed on preoperative radiographs was 100 % ( 11 of 11 ) among patients with fractures compared with 33.3 % ( 9 of 27 ) of patients without fracture ( p=.0001 ) . Overall , 21 of 39 patients in this series had spondylolisthesis , and the rate of fracture in this group was 52 % . Among patients without spondylolisthesis , the fracture rate was 0 % . A trend was observed toward decreased DXA lumbar spine and hip T-scores among fracture patients versus nonfracture patients ( 0.2 ± 1.7 vs. 0.8 ± 1.7 ; p=.389 ; -1.1 ± 1.4 vs. -0.3 ± 1.4 ; p=.201 ) , but these differences were not significant . Similarly , bone density based on CT measurements at four different locations revealed a trend toward decreased density among fracture patients , but these differences were not significant . CONCLUSIONS Degenerative spondylolisthesis appears strongly associated with the occurrence of spinous process fracture after IPS surgery . There is a trend toward increased fracture risk in patients with decreased bone mineral density as measured by both DXA scan and CT-based volume averaging of Hounsfield units , but osteoporosis appears to be a relatively weaker risk factor . The association between spondylolisthesis and fracture observed in this study may account for the relatively poorer outcome of IPS surgery in patients with spondylolisthesis that has been reported in previous series BACKGROUND Vascular calcification ( VC ) contributes to cardiovascular disease in haemodialysis ( HD ) patients . Few controlled studies have addressed interventions to reduce VC but non-calcium-based phosphate binders may be beneficial . No published r and omized study to date has assessed the effect of lanthanum carbonate ( LC ) on VC progression . METHODS We conducted a pilot r and omized controlled trial to determine the effect of LC on VC . Forty-five HD patients were r and omized to either LC or calcium carbonate ( CC ) . Primary outcome was change in aortic VC after 18 months . Secondary outcomes included superficial femoral artery ( SFA ) VC , bone mineral density ( BMD ) of lumbar spine and serum markers of mineral metabolism . At baseline , 6 and 18 month computed tomography was performed to measure VC and BMD . A r and om effect linear regression model was performed to assess differences . RESULTS Thirty patients completed the study ( 17 LC , 13 CC ) ; baseline median age 58 years , 38 % diabetic , 64 % male . Ninety-three per cent had aortic VC at commencement and 87 % showed progression . At 18 months , there was significantly less aortic VC progression with LC than CC ( adjusted difference -98.1 ( -149.4 , -46.8 ) Hounsfield units ( HU ) , P < 0.001 ) . There was also a non-significant reduction with LC in left SFA VC ( -25.8 ( -67.7 , 16.1 ) HU , P = 0.2 ) and right SFA VC ( -35.9 ( -77.8 , 5.9 ) HU , P = 0.09 ) . There was no difference in lumbar spine BMD and serum phosphate , calcium and parathyroid hormone levels between groups . Limitations to the study include small sample size and loss to follow up . CONCLUSIONS Lanthanum carbonate was associated with reduced progression of aortic calcification compared with CC in HD patients over 18 months In the United States , Medicare gradually reduced payments for central dual-energy X-ray absorptiometry ( DXA ) performed at physician offices ( or other nonhospital setting s ) from an average of $ 139 in 2006 to about $ 82 in 2007 and 2008 and $ 72 in 2009 . Reimbursement for hospital outpatient DXA service was unchanged . We investigated the utilization of hip and spine ( central ) DXA in the Medicare population before and after the reduction . We identified individuals from the national 5 % r and om sample of Medicare beneficiaries who were ≥65 years of age and enrolled in Medicare Parts A and B but not in a Medicare Advantage plan from 2002 through 2009 . For each calendar year , we calculated the proportion of beneficiaries who su bmi tted cl aims for DXA , the proportions of DXAs performed in hospitals and in physician offices and the number of physician office-based practice s that discontinued or started to provide DXA services . From 2002 to 2006 , the proportion of beneficiaries who had at least one central DXA increased from 7.9 % to 9.6 % at an annual increase of 0.4 % and from 2006 to 2009 , the annual increase dropped to 0.1 % . The number of DXAs performed in physician offices dropped from 1,643,720 ( 69 % of 2,363,500 total DXAs ) in 2006 to 1,534,240 ( 66 % of 2,338,240 ) in 2009 . This decline was offset by an increase in the number of DXAs performed in hospitals , which increased from 719,780 ( 31 % ) in 2006 to 804,000 ( 34 % ) in 2009 . Among physician office-based practice s , more practice s initiated than discontinued DXA service each year from 2002 to 2006 . However , the trend was reversed since 2007 such that in 2009 , 1876 practice s discontinued and only 1394 initiated DXA service . The reduction in DXA reimbursement was associated with a decrease in the number of DXAs performed in physician offices and fewer physician offices that provided DXA services Background : A cannulated lag screw inserted through the medial cuneiform into the base of the second metatarsal is often utilized to reduce the diastasis and aid healing of Lisfranc injuries . Also procedures such as a midfoot or a Lapidus arthrodesis require adequate implant-bone purchase in the medial cuneiform . The medial cuneiform contains cancellous bone of varying density . Knowledge of density variation may be helpful for implant usage and manufacturing of area specific implants . Methods : In 60 r and omly selected patients , mean computed tomography ( CT ) intensity in Hounsfield units was measured at 12 sample d locations within the medial cuneiform and served as a proxy for bone density . The patients ’ age , gender , and race were recorded . An analysis of variance ( ANOVA ) assessed the effect of age , gender , race , and sample site on bone density . Statistical testing assumed 95 % level of confidence . Results : ANOVA showed age , gender , and sample site had significant effects ( P < .001 ) on bone density , though race had no significant effect ( P = .28 ) . The distal-dorsal-lateral ( DDL ) site was significantly denser than all other sites ( P < .001 ) except the middle-dorsal-lateral ( MDL ) ( P = .53 ) . The proximal-plantar-lateral ( PPL ) site was significantly less dense than all other sites ( P < .001 ) except the middle-plantar-lateral/medial and the proximal-plantar-medial sites ( P < .14 ) . A general trend of density increasing in the distal and dorsal directions was evident , and within the dorsal sites there was a trend of increasing density in the lateral direction . Conclusion : This is the first study to date to measure density of the medial cuneiform using living subjects . The sample size of 60 patients was also the largest of any study measuring density of this bone . We conclude that the densest area of the medial cuneiform is the most anterior , dorsal , and lateral portion . Clinical Relevance : The findings of this study may indicate the most optimal area for implant purchase in the medial cuneiform when reducing the diastasis between the base of the second metatarsal and medial cuneiform and for stabilization of the medial column Osteoporosis is highly prevalent in chronic obstructive pulmonary disease ( COPD ) patients and has been related to several clinical features . However , most studies have been in relatively small COPD cohorts . Therefore , the objectives of this study were to compare bone attenuation measured on low-dose chest computed tomography ( CT ) between COPD subjects and smoker and nonsmoker controls , and to relate bone attenuation to clinical parameters , inflammatory biomarkers , and outcomes in a large , well-characterized COPD cohort . We studied 1634 COPD subjects , 259 smoker controls , and 186 nonsmoker controls who participated in a large longitudinal study ( ECLIPSE ) . We measured bone attenuation , extent of emphysema , and coronary artery calcification ( Agatston score ) on baseline CT scans , and clinical parameters , inflammatory biomarkers , and outcomes . Bone attenuation was lower in COPD subjects compared with smoker and nonsmoker controls ( 164.9 ± 49.5 Hounsfield units [ HU ] versus 183.8 ± 46.1 HU versus 212.1 ± 54.4 HU , p < 0.001 ) . Bone attenuation was not significantly different between COPD subjects and smoker controls after adjustment for age , sex , and pack-years of smoking . In the COPD subjects , bone attenuation correlated positively with forced expiratory volume in 1 second ( FEV₁ , r = 0.062 , p = 0.014 ) , FEV₁/forced vital capacity ( FVC ) ratio ( r = 0.102 , p < 0.001 ) , body mass index ( r = 0.243 , p < 0.001 ) , fat-free mass index ( FFMI , r = 0.265 , p < 0.001 ) , and C-reactive protein ( r = 0.104 , p < 0.001 ) , and correlated negatively with extent of emphysema ( r = -0.090 , p < 0.001 ) , Agatston score ( r = -0.177 , p < 0.001 ) , and interleukin-8 ( r = -0.054 , p = 0.035 ) . In a multiple regression model , older age , lower FFMI and higher Agatston score were associated with lower bone attenuation . Lower bone attenuation was associated with higher exacerbation ( r = -0.057 , p = 0.022 ) and hospitalization ( r = -0.078 , p = 0.002 ) rates but was not associated with all-cause mortality . In conclusion , CT-measured bone attenuation was lower in COPD subjects compared with nonsmoker controls but not compared with smoker controls , after adjustment for age , sex , and pack-years of smoking . In the COPD subjects , bone attenuation was associated with age , body composition , and coronary artery calcification but was not associated with all-cause mortality |
12,852 | 30,186,067 | Conclusion From extensive literature search , there was no strong evidence indicating the positive effect of mechanical stretch using stretching exercise , massage , or splinting on hypertrophic scars .
A firm conclusion can not be drawn for the discrepancy of outcome measures and varied effectiveness . | Objective / Background To review the effect of mechanical stretch on hypertrophic scars after burn injuries . | Background : How a scar is managed postoperatively influences its cosmetic outcome . After suture removal , scars are susceptible to skin tension , which may be the trigger for hypertrophic scarring . Paper tape to support the scar may reduce multidirectional forces and prevent hypertrophic scarring . Methods : Seventy patients who had undergone cesarean section at the Royal Brisbane and Women 's Hospital were r and omized to treatment and control groups . Patients in the control group received no postoperative intervention . Patients in the treatment group applied paper tape to their scars for 12 weeks . Scars were assessed at 6 weeks , 12 weeks , and 6 months after surgery using ultrasound to measure intradermal scar volume . Scars were also assessed using the International Clinical Recommendations . Results : Paper tape significantly decreased scar volume by a mean of 0.16 cm3 , ( 95 percent confidence interval , 0.00 to 0.29 cm3 ) . At 12 weeks after surgery , 41 percent of the control group developed hypertrophic scars compared with none in the treatment group ( exact test , p = 0.003 ) . In the treatment group , one patient developed a hypertrophic scar and four developed stretched scars only after the tape was removed . The odds of developing a hypertrophic scar were 13.6 times greater in the control than in the treatment group ( 95 percent confidence interval , 3.6 to 66.9 ) . Of the 70 patients r and omized , 39 completed the study . Four patients in the treatment group developed a localized red rash beneath the tape . These reactions were minor and transient and resolved without medical intervention . Conclusions : The development of hypertrophic and stretched scars in the treatment group only after the tape was removed suggests that tension acting on a scar is the trigger for hypertrophic scarring . Paper tape is likely to be an effective modality for the prevention of hypertrophic scarring through its ability to eliminate scar tension Hypertrophic scars ( HTS ) , the excessive deposition of scar tissue by fibroblasts , is one of the most common skin disorders . Fibroblasts derived from surgical scar tissue produce high levels of α-smooth muscle actin ( α-SMA ) and transforming growth factor-β1 ( TGF-β1 ) . However , the molecular mechanisms for this phenomenon is poorly understood . Thus , the purpose of this study was to evaluate the molecular mechanisms of HTS and their potential therapeutic implication s. Fibroblasts derived from skin HTS were cultured and characterized in vitro . The fibroblasts were synchronized and r and omly assigned to two groups : cyclic stretch and cyclic stretch pre-treated with SB203580 ( a p38MAPK inhibitor ) . Cyclic stretch at 10 % strain was applied at a loading frequency of 10 cycles per minute ( i.e. 5 seconds of tension and 5 seconds of relaxation ) for 0 h , 6 h and 12 h. Cyclic stretch on HTS fibroblasts led to an increase in the expression of α-SMA and TGF-β1 mRNA and protein and the phosphorylation of p38MAPK . SB203580 reversed these effects and caused a decrease in matrix contraction . Furthermore , HTS fibroblast growth was partially blocked by p38MAPK inhibition . Therefore , the mechanism of cyclic stretch involves p38 MAPK , and its inhibition is suggested as a novel therapeutic strategy for HTS PURPOSE Hypertrophic scarring and depression are the principal problems of burn rehabilitation . This study was done to verify the effects of skin rehabilitation massage therapy ( SRMT ) on pruritus , skin status , and depression for Korean burn survivors . METHODS A pretest-posttest design using a nonequivalent control group was applied to examine the effects of SRMT for 3 months in a group of 18 burn survivors . The major dependent variables-including pruritus , objective and subjective scar status , and depression-were measured at the beginning and at the end of the therapy to examine the effects of SRMT . RESULTS Burn survivors receiving SRMT showed reduced pruritus , improved skin status , and depression . The remaining scar also showed improvement in skin pigmentation , pliability , vascularity , and height ( compared to the surrounding skin ) as measured on the Vancouver Scar Scale ( VSS ) . CONCLUSIONS The findings demonstrate that SRMT for burn survivors may improve their scars both objective ly and subjectively , and also reduce pruritus and depression Transforming growth factor beta 1 ( TGF-beta1 ) plays a key role in connective tissue remodeling , scarring , and fibrosis . The effects of mechanical forces on TGF-beta1 and collagen deposition are not well understood . We tested the hypothesis that brief ( 10 min ) static tissue stretch attenuates TGF-beta1-mediated new collagen deposition in response to injury . We used two different models : ( 1 ) an ex vivo model in which excised mouse subcutaneous tissue ( N = 44 animals ) was kept in organ culture for 4 days and either stretched ( 20 % strain for 10 min 1 day after excision ) or not stretched ; culture media was assayed by ELISA for TGF-beta1 ; ( 2 ) an in vivo model in which mice ( N = 22 animals ) underwent unilateral subcutaneous microsurgical injury on the back , then were r and omized to stretch ( 20 - 30 % strain for 10 min twice a day for 7 days ) or no stretch ; subcutaneous tissues of the back were immunohistochemically stained for Type-1 procollagen . In the ex vivo model , TGF-beta1 protein was lower in stretched versus non-stretched tissue ( repeated measures ANOVA , P < 0.01 ) . In the in vivo model , microinjury result ed in a significant increase in Type-1 procollagen in the absence of stretch ( P < 0.001 ) , but not in the presence of stretch ( P = 0.21 ) . Thus , brief tissue stretch attenuated the increase in both soluble TGF-beta1 ( ex vivo ) and Type-1 procollagen ( in vivo ) following tissue injury . These results have potential relevance to the mechanisms of treatments applying brief mechanical stretch to tissues ( e.g. , physical therapy , respiratory therapy , mechanical ventilation , massage , yoga , acupuncture ) INTRODUCTION Exercises are commonly prescribed to improve shoulder range following axillary burns , but the effect of additional splinting is unclear . AIM To compare splinting and exercise to exercise alone in adults with axillary burns . METHOD Prospect i ve r and omised study allocating participants to a splinting ( n=27 ) or no splinting group ( n=25 ) . Outcomes measured at six and twelve weeks were shoulder abduction and flexion range , quality of life using the Burn Specific Health Scale-Brief ( BSHS-B ) question naire and upper limb function using the Upper Extremity Functional Index ( UEFI ) and the Grocery Shelving Task ( GST ) . RESULTS At week twelve , there was no difference between groups for shoulder abduction ( mean difference 0 ° , 95 % CI -22 to 22 ° ) , flexion ( mean difference 2 ° , 95 % CI -18 to 23 ° ) , BSHS-B ( mean difference -2 points , 95 % CI -23 to 18 points ) , UEFI ( mean difference -3 points , 95 % CI -19 to 14 points ) and GST ( mean difference -9s , 95 % CI -20 to 3s ) . Adherence to splinting decreased from 77 % of participants at week one to 16 % at week twelve . CONCLUSION Shoulder splints did not improve clinical outcomes in this study population and low adherence rates suggest splinting may be unacceptable to patients and makes drawing firm conclusions difficult OBJECTIVE To evaluate the effect of burn rehabilitation massage therapy on hypertrophic scar after burn . METHOD One hundred and forty-six burn patients with hypertrophic scar(s ) were r and omly divided into an experimental group and a control group . All patients received st and ard rehabilitation therapy for hypertrophic scars and 76 patients ( massage group ) additionally received burn scar rehabilitation massage therapy . Both before and after the treatment , we determined the scores of visual analog scale ( VAS ) and itching scale and assessed the scar characteristics of thickness , melanin , erythema , transepidermal water loss ( TEWL ) , sebum , and elasticity by using ultrasonography , Mexameter ( ® ) , Tewameter ( ® ) , Sebumeter ( ® ) , and Cutometer ( ® ) , respectively . RESULTS The scores of both VAS and itching scale decreased significantly in both groups , indicating a significant intragroup difference . With regard to the scar characteristics , the massage group showed a significant decrease after treatment in scar thickness , melanin , erythema , TEWL and a significant intergroup difference . In terms of scar elasticity , a significant intergroup difference was noted in immediate distension and gross skin elasticity , while the massage group significant improvement in skin distensibility , immediate distension , immediate retraction , and delayed distension . CONCLUSION Our results suggest that burn rehabilitation massage therapy is effective in improving pain , pruritus , and scar characteristics in hypertrophic scars after burn 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 . & NA ; The objective of this study was to identify the effects of a skin rehabilitation nursing program ( SRNP ) on skin status , depression , and burn‐specific health in Korean burn survivors . A pretest‐posttest design with a nonequivalent control group was used to examine the effects of SRNP for 3 months in a group of 26 burn survivors . The SRNP group of 13 burn survivors received massage therapy 30 minutes three times a week for 3 months compared to a control group of 13 burn survivors receiving typical care . The SRNP group showed no significant changes in the burn scar , subjective skin status , depression , or burn‐specific health . Burn survivors receiving SRNP had reduced burn scar depth after the intervention compared to the control group . The findings of this study demonstrate that SRNP for burn survivors may improve burn scars , and findings suggest that future studies with a larger sample should be conducted using SRNP as an intervention for burn survivors INTRODUCTION Injury from burns is very common and must be treated with considerable care by the rehabilitation team to prevent contractures that may occur . Physiotherapy is vital in rehabilitation of burn-injured patients . PURPOSE The aim of this study is to compare a burn rehabilitation treatment ( BRT ) protocol with a routine burn rehabilitation treatment to find out rehabilitation related problems . METHODS For all burn-injured patients admitted to a general hospital in Tehran on 2005 , a group match clinical trial was done and then r and omly divided into two groups . For the first group , ordinary physiotherapy was done according to the routine prescription and the BRT protocol has been carried out for the second group . At the time of patient registration , a question naire was completed which consisted of gender , age , TBS , depth and cause of injury . On the other h and , post burn contractures , thrombosis and duration of staying in hospital was measured at discharge . RESULTS There was not any significant difference ( p>0.05 ) in gender , age , TBS , cause and depth of injury between two groups . In addition , there was not any significant difference ( p>0.05 ) between thrombosis and duration of staying patients in hospital . However , these results show significant difference ( p<0.01 ) in burn contractures between two groups . In the BRT group , 6 % had burn contractures , with 73 % routine rehabilitation treatment . CONCLUSION The result of this study indicates that intensive rehabilitation decreased burn complications . Burn rehabilitation teams could consider the BRT protocol Various attempts have been made to intervene with the formation of hypertrophic scarring ( HTS ) or to ameliorate it once it has developed , but none have yet proved effective . Massage therapy is routinely used by therapists for the treatment of various conditions , and there have been reports of increased scar pliability and decreased scar b and ing with the use of massage . This study examines the use of friction massage over a 3-month period in a group of 30 pediatric patients with HTS . The patients were r and omly assigned to receive either therapeutic massage sessions of 10 minutes per day in combination with treatment with pressure garments or they were treated with pressure garments alone . A modified Vancouver Burn Scar Assessment Scale was used to measure the characteristics of the identified scars ( 10 cm by 10 cm ) before and after the implementation of massage therapy . The study failed to demonstrate any appreciable effects of massage therapy on the vascularity , pliability , and height of the HTS studied , although there were reports of a decrease in pruritus in some patients . Further studies , with prolonged treatment intervals , are necessary to conclusively demonstrate the ineffectiveness of this therapy for HTS |
12,853 | 30,448,929 | IV and local steroids statistically significant decrease immediate post-operative pain severity .
Local steroids had extended effect in reducing pain scores on the first day after tonsillectomy .
However , the clinical significance of pain relief had to be concerned due to decreasing VAS only about 1 out of 10 .
Adding oral steroids to IV steroids gave no difference in effect from IV steroids alone .
Steroids have no statistically significant effect in reducing pain severity after a 1-day period .
Conclusion Intravenous steroids statistically significantly decrease post-tonsillectomy nausea/vomiting , and immediate pain scores ( < 24 h ) in children and adults .
There is evidence in only children that local steroids statistically significantly decreases post-tonsillectomy nausea/vomiting , and pain scores during the 0-h to 1-day period | Objectives To systemically review and compare the efficacy of intravenous , local , and oral steroids in decreasing post-tonsillectomy pain , nausea , and vomiting , and its risk of causing hemorrhage . | CONTEXT Corticosteroids are commonly given to children undergoing tonsillectomy to reduce postoperative nausea and vomiting ; however , they might increase the risk of perioperative and postoperative hemorrhage . OBJECTIVE To determine the effect of dexamethasone on bleeding following tonsillectomy in children . DESIGN , SETTING , AND PATIENTS A multicenter , prospect i ve , r and omized , double-blind , placebo-controlled study at 2 tertiary medical centers of 314 children aged 3 to 18 years undergoing tonsillectomy without a history of bleeding disorder or recent corticosteroid medication use and conducted between July 15 , 2010 , and December 20 , 2011 , with 14-day follow-up . We tested the hypothesis that dexamethasone would not result in 5 % more bleeding events than placebo using a noninferiority statistical design . INTERVENTION A single perioperative dose of dexamethasone ( 0.5 mg/kg ; maximum dose , 20 mg ) , with an equivalent volume of 0.9 % saline administered to the placebo group . MAIN OUTCOME MEASURES Rate and severity of posttonsillectomy hemorrhage in the 14-day postoperative period using a bleeding severity scale ( level I , self-reported or parent-reported postoperative bleeding ; level II , required inpatient admission for postoperative bleeding ; or level III , required reoperation to control postoperative bleeding ) . RESULTS One hundred fifty-seven children ( median [ interquartile range ] age , 6 [ 4 - 8 ] years ) were r and omized into each study group , with 17 patients ( 10.8 % ) in the dexamethasone group and 13 patients ( 8.2 % ) in the placebo group reporting bleeding events . In an intention-to-treat analysis , the rates of level I bleeding were 7.0 % ( n = 11 ) in the dexamethasone group and 4.5 % ( n = 7 ) in the placebo group ( difference , 2.6 % ; upper limit 97.5 % CI , 7.7 % ; P for noninferiority = .17 ) ; rates of level II bleeding were 1.9 % ( n = 3 ) and 3.2 % ( n = 5 ) , respectively ( difference , -1.3 % ; upper limit 97.5 % CI , 2.2 % ; P for noninferiority < .001 ) ; and rates of level III bleeding were 1.9 % ( n = 3 ) and 0.6 % ( n = 1 ) , respectively ( difference , 1.3 % ; upper limit 97.5 % CI , 3.8 % ; P for noninferiority = .002 ) . CONCLUSIONS Perioperative dexamethasone administered during pediatric tonsillectomy was not associated with excessive , clinical ly significant level II or III bleeding events based on not having crossed the noninferior threshold of 5 % . Increased subjective ( level I ) bleeding events caused by dexamethasone could not be excluded because the noninferiority threshold was crossed . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01415583 OBJECTIVE To determine the effect of preoperative dexamethasone sodium phosphate administration on posttonsillectomy morbidity for electrocautery ( " hot " ) and sharp ( " cold " ) dissection techniques . DESIGN Prospect i ve , r and omized , double-blind study . SETTING University pediatric hospital and county teaching hospital . Subjects A total of 219 children , aged 9 months to 12 years , undergoing tonsillectomy . Intervention Participants who underwent tonsillectomy were r and omly assigned to receive either intravenous dexamethasone sodium phosphate ( 1 mg/kg ) or placebo . OUTCOME MEASURES Pain scores , oral intake , and emesis on postoperative day ( POD ) 1 . RESULTS A total of 106 subjects ( 62 undergoing hot and 44 cold tonsillectomies ) received preoperative steroids , and 113 ( 56 hot and 57 cold tonsillectomies ) received placebo . On POD 1 , pain scores reported by patients ( P = .02 ) , parents ( P = .002 ) , and physicians ( P<.001 ) were significantly lower in subjects receiving steroids than in those receiving placebo . Emesis was reduced from a mean of 2.1 ( placebo group ) to 1.2 episodes ( steroid group ) ( P = .02 ) . Oral intake improved from 24.5 % of normal diet ( placebo ) to 31.7 % ( steroid group ) ( P = .004 ) . When all 4 groups were compared ( cold placebo , cold steroid , hot placebo , and hot steroid ) , pain scores reported by physicians and parents were significantly lower in the cold steroid group than in the other groups . CONCLUSIONS Perioperative dexamethasone use reduces posttonsillectomy morbidity in pediatric patients in the early postoperative period after hot or cold tonsillectomy . The combination of steroid and cold dissection technique provided the greatest advantage in reducing posttonsillectomy subjective pain levels OBJECTIVE To evaluate the effects of a single pre-operative dose of dexamethasone with the frequency of postoperative vomiting and severity of throat pain in children undergoing electrocautery tonsillectomy under st and ard general anaesthesia . STUDY DESIGN R and omised controlled trial . PLACE AND DURATION OF STUDY ENT Department , Combined Military Hospital , Kharian , from January to December 2010 . METHODOLOGY Children of either gender aged between 4 - 12 years , undergoing tonsillectomy were divided into two groups of 50 each . One group was selected to receive dexamethasone 0.5 mg/kg ( maximum of 8 mg ) ; the second group was given equivalent volume of saline , pre-operatively . The frequency of early and late vomiting was assessed postextubation . Mean time of first oral intake in minutes after extubation and mean score of postoperative throat pain were compared in both groups . Severity of throat pain was monitored by Visual Analogue Scale ( VAS ) score 0 - 10 after 4,8,12 and 24 hours of extubation . RESULTS Dexamethasone group showed significantly less postoperative early vomiting ( 12 % , n = 6 ) as compared to placebo ( 30 % , n = 15 ) group ( p < 0.05 ) . The mean time of first oral intake was earlier in the dexamethasone group ( 4 hours and 16 minutes postextubation ) , while in saline group it was 5 hours and 20 minutes ( p < 0.001 ) . Pain score was also significantly lower and swallowing was less painful in patients after 4,8,12 and 24 hours in dexamethasone group . Pain score on the average was 0.8 - 1.2 factors less in dexamethasone group than in saline group in first 24 hours on a VAS score of 1 -10 . CONCLUSION Pre-operative intravenous dexamethasone reduced postoperative vomiting and pain significantly in children undergoing electrocautery tonsillectomy Edema contributes substantially to the postoperative discomfort and morbidity of adenotonsillectomy . In a double-blind study , 58 children undergoing adenotonsillectomy were given a single intraoperative dose of either dexamethasone or saline . The steroid markedly affected the postoperative course in the first day after surgery . According to parental reports , the percentage of patients vomiting was reduced from 48 to 4 % . Severe throat pain was reported in 57 % of controls and only 20 % of dexamethasone patients . Twice as many steroid patients as controls tolerated some soft food on the first postoperative day . It appears that dexamethasone can greatly improve patient diet and comfort after adenotonsillectomy OBJECTIVE To determine whether a single intraoperative dose of intravenous dexamethasone has an effect on pain after tonsillectomy . DESIGN Double-blinded r and omized controlled clinical trial . SUBJECTS Thirty-four consecutive nonpediatric patients presenting for tonsillectomy . INTERVENTION Patients scheduled for electrocautery tonsillectomy were r and omized to receive either intravenous dexamethasone or placebo during surgery . Pain was measured twice daily for 10 days by means of a visual analog scale . RESULTS There were no statistically significant differences between the groups , but the dexamethasone group had a trend to report less pain over the first several days . The dexamethasone group received less analgesic in the recovery room , but there were no differences between the groups in the 10 days afterward . CONCLUSIONS There is evidence that a single dose of dexamethasone reduces pain after tonsillectomy to a small degree . A single dose was not associated with adverse effects , so the risk-benefit ratio may be favorable for this practice Objective : The aim of the study is to evaluate the efficacy of peritonsillar infiltration of a levobupivacaine hydrochloride and dexamethasone combination for post-tonsillectomy pain in adult patients . Methods : A total of 40 patients were included in this double-blind , r and omized , and placebo-controlled study . The patients were equally r and omized into 2 groups by means of sealed envelopes . The study group ( SG ) received peritonsillar levobupivacaine hydrochloride and dexamethasone infiltration and the control group ( CG ) received peritonsillar saline infiltration . Pain scores at the second , fourth , eighth , 12th , 16th , and 24th hours and the second to seventh days after operation were recorded by the patients in each group using a visual analog scale . Duration of surgery and the total amount of blood loss during the surgery were also recorded for each patient . Results : All pain scores in the SG were lower than those in the CG ; however , the difference was significant at the second , 12th , and 16th hours , and the second and third day ( P < 0.05 ) . Postoperative morbidity parameters , including otalgia , nausea , vomiting , fever , halitosis , and bleeding were similar between the 2 groups . Total amount of analgesic consumption in the SG was significantly lower than in the CG on each day of the week after tonsillectomy . Conclusions : Peritonsillar infiltration of a levobupivacaine hydrochloride and dexamethasone combination may provide pain reduction and decrease analgesic consumption in the postoperative period after adult tonsillectomy OBJECTIVE To assess the effect of a course of intravenous dexamethasone on pain after tonsillectomy . METHOD Sixty patients who underwent tonsillectomy or adenoidectomy and tonsillectomy were r and omly divided into experimental group and control group . Postoperatively , 30 patients in experimental group received anti-inflammatory drug and dexamethasone for 4 days , and the other 30 patients in control group received anti-inflammatory drug and placebo . Degree of postoperative pain was measured with visual analogue scale in the patients more than 12-year-old and with Wong-Baker faces pain scale in the patients less than or equal to 12-year-old . The measurement was made twice daily for 5 days . RESULT During the postoperative period , the scale value was decreasing every day in the all patients . But the value in experimental group was less than that in control group , and the difference was statistically significant ( P<0.05 ) . CONCLUSION Dexamethasone given in this regime reduces postoperative pain and odynophagia after tonsillectomy Tonsillectomy is one of the most frequently performed ambulatory surgical procedures in children ( Litman et al. in Anesth Analg 78:478–481 , 1994 ) . Several techniques have been described for alleviation of pain ( Ginstrom et al. in Acta Otolaryngol 125:972–975 , 2005 ) . the objective of this study determination of the postoperative analgesic efficacy of the pre-surgical intravenous administration of dexamethasone together with glossopharyngeal nerve block ( GNB ) in children undergoing tonsillectomy . Prospect i ve double blind r and omized control study using both pre-operative injection of 0.5 mg/kg dexamethasone iv and 3 ml of 0.5 % bupivacaine local injection for bilateral glossopharyngeal nerve block . Patients in group B had significantly less visual analogue scale values , longer absolute analgesia time , lesser swallowing difficulty and they were discharged earlier from the hospital when compared to patients in both groups D and G. Using both pre-operative dexamethasone IV injection with GNB has reduced postoperative pain and morbidity to a great extent than using either alone A prospect i ve , r and omized , double-blinded , placebo-controlled clinical trial was conducted in 41 patients evaluating the effect of a single preoperative dose of intravenous dexamethasone on postoperative vomiting and pain in children undergoing elective tonsillectomy . Dexamethasone was found to significantly reduce the incidence of vomiting in the first 24 hours postoperatively ( P=0.02 ) , the time to first intake of solids ( P=0.001 ) , the need to administer a rescue antiemetic ( P=0.005 ) and intravenous fluid therapy requirements ( P=0.006 ) in the postoperative period . No significant difference was found between the dexamethasone and placebo groups in the time to first intake of fluids , pain scores or analgesic requirement postoperatively . These results indicate that dexamethasone substantially reduces morbidity after tonsillectomy in children In this prospect i ve , r and omized , double-blind , placebo-controlled study , we examined the effect of preoperative dexamethasone on postoperative nausea and vomiting ( PONV ) and 24-h recovery in children undergoing tonsillectomy . One hundred thirty children , 2 - 12 yr of age , ASA physical status I or II , completed the study . All children received oral midazolam 0.5 - 0.6 mg/kg preoperatively . Anesthesia was induced with halothane and nitrous oxide in 60 % oxygen and maintained with nitrous oxide and isoflurane . Intubation was facilitated by mivacurium 0.2 mg/kg . Each child received fentanyl 1 [ micro sign]g/kg IV before initiation of surgery , as well as dexamethasone 1 mg/kg ( maximal dose 25 mg ) ( steroid group ) or an equal volume of saline ( control group ) . Intraoperative fluids were st and ardized to 25 - 30 mL/kg lactated Ringer 's solution . All tonsillectomies were performed under the supervision of one attending surgeon using an electrodissection technique . Postoperatively , fentanyl and acetaminophen with codeine elixir were administered as needed for pain . Rescue antiemetics were administered when a child experienced two episodes of retching and /or vomiting . Before home discharge , the incidence of PONV , need for rescue antiemetics , quality of oral intake , and analgesic requirements did not differ between groups . However , during the 24 h after discharge , more patients in the control group experienced PONV ( 62 % vs 24 % in the steroid group ) and complained of poor oral intake . Additionally , more children in the control group ( 8 % vs 0 % in the steroid group ) returned to the hospital for the management of PONV and /or poor oral intake . The preoperative administration of dexamethasone significantly decreased the incidence of PONV over the 24 h after home discharge in these children . Implication s : In this double blind , placebo-controlled study , we examined the efficacy of a single large dose ( 1 mg/kg ; maximal dose 25 mg ) of preoperative dexamethasone on posttonsillectomy postoperative nausea and vomiting ( PONV ) in children 2 - 12 yr of age undergoing tonsillectomy . Compared with placebo , dexamethasone significantly decreased the incidence of PONV in the 24 h after discharge , improved oral intake , decreased the frequency of parental phone calls , and result ed in no hospital returns for the management of PONV and /or poor oral intake . ( Anesth Analg 1998;87:57 - 61 This prospect i ve study was done for to see the efficacy of preoperative use of granisetron plus dexamethasone ( Group A ) & granisetron ( Group B ) alone for the postoperative prevention of nausea & vomiting after tonsillectomy operation . One hundred patients undergoing tonsillectomy & adenoidectomy operation under general anaesthesia who were admitted in the Mymensingh Medical College Hospital during the period from July 2008 to June 2009 with American Society of Anaesthesiologists ( ASA ) grade I & II with age 3 - 40 years , body weight 10 - 60 kgs , were studied . Observation of this study was analyzed in the light of comparison between the two groups . All results were expressed as mean±SEM . Age in Group A 15.98±1.028 & Group B 17.18±0.961 years ; Weight in Group A 38.40±1.492 & Group B 39.76±1.561 kgs and operational duration in Group A 52.60±0.786 & Group B 52.70±0.823 minutes . The studied groups were statistically matched for age , weight , duration of surgery . We observed that the effects of combination of granisetron & dexamthasone are more than granisetron alone in prevention of nausea & vomiting after tonsillectomy operation . The frequency of vomiting was 4 % in combination & 16 % in single therapy which is statically significant ( p<0.05 ) Summary Background Surface electromyographic ( sEMG ) study of post-tonsillectomy swallow-evoked muscular reactions was performed in order to evaluate the efficacy and safety of oxycodone and dexamethasone in pain management after tonsillectomy . Material / Methods 90 r and omly chosen operated adults were divided into three groups . Group 1 ( n=30 ) was treated with OxyContin ( Oxycodone ) injections ; Group 2 ( n=30 ) was treated with Dexacort ( Dexamethasone ) , and Group 3 ( n=30 ) was a placebo group . Pain assessment included visual analogue scale ( VAS ) pain score and the EMG data like the timing , electric amplitude and graphic patterns of muscular activity during deglutition . We investigated masseter , infrahyoid and submental-subm and ibular muscles . Records from trapezius muscle were used for control . The results were compared with previously established normative data base . The patients were tested 24 h after surgery . The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients . Results Analgesia with oxycodone smoothed the recorded sEMG swallow peaks and increases time of deglutition . Dexamethasone normalized muscular activity in deglutition in cases with edema as detected by the EMG records . Statistically significant difference in muscle reactions was detected between the two Groups and the placebo group . Conclusions Application of oxycodone significantly reduces the postoperative pain . Application of dexamethasone after tonsillectomy is advisable because of the reduction of postoperative morbidity while the reduction of the postoperative pain is secondary to the reduction of edema . SEMG might be used as an adjunctive measure of pain behavior via assessment of muscular reactions to pain and to analgesia OBJECTIVE To determine the effects of a single dose of dexamethasone sodium phosphate on postoperative morbidity in children undergoing tonsillectomy . DESIGN R and omized , double-blind , placebo-control clinical trial . SETTING Academic , tertiary care children 's hospital . PATIENTS Sixty-nine children ( 35 boys , 34 girls ) , aged 3 to 18 years , undergoing tonsillectomy with or without adenoidectomy . INTERVENTION Patients were r and omized to receive a single dose of intravenous dexamethasone or saline . MAIN OUTCOME MEASURES Pain scores , determined by a Faces Scale , were obtained at 4-hour intervals during the first postoperative day and daily for 7 days thereafter . Total use of an analgesic ; type of diet ; level of activity ; presence of halitosis , nausea , emesis , or fever ; and incidence of postoperative bleeding were also compared between the two groups . RESULTS The two groups of children were similar in age , gender , diagnosis , and surgical time . Pain scores in the postoperative period were identical while the patients were in the hospital and for the first 7 days after discharge . No statistically significant differences were noted in pain scores , nausea , emesis , halitosis , analgesic medications required , diet , or activity levels between the two groups of patients . CONCLUSION A single intraoperative dose of dexamethasone did not appreciably affect postoperative morbidity in children undergoing tonsillectomy OBJECTIVE Vomiting is one of the most important postoperative complications of adenotonsillectomy . This study was design ed to determine the effectiveness of preoperative intravenous dexamethasone on postoperative emesis . METHODS In a double-blind , placebo-controlled clinical trial , 100 patients aged 5 - 15 years , ASA classes I and II were r and omly selected to receive either 0.5 mg/kg IV dexamethasone ( n=50 ) , as study group or an equivalent volume of saline preoperatively , as control group . The anesthetic regimen and surgical procedures were st and ardized for all patients . The incidence of early and late vomiting , the time to first oral intake and duration of intravenous hydration were compared in both groups . RESULTS Data analysis showed that the overall incidence of early and late vomiting was significantly lesser in dexamehasone group than the control one . The time to first oral intake and duration of IV therapy were also significantly shorter in dexamethasone group . CONCLUSION A single dose of dexamethasone significantly decreased the incidence of postoperative vomiting in early and late recovery phase and shortened the time to first oral intake and the duration of IV therapy BACKGROUND Previous studies on dexamethasone 's antiemetic and antinflammatory potential in patients undergoing adenotonsillectomy have produced conflicting results . OBJECTIVES To determine the effect of intraoperative I.V. single dose dexamethasone on recovery and complications after adenotonsillitis while anesthesia techniques , surgical techniques and perioperative treatment are st and ardized . DESIGN Prospect i ve r and omized , controlled study . METHODS A total of 230 patients aged 2 - 16 years undergoing elective adenotonsillectomy enrolled in the study . Patients were r and omly assigned to receive i.v . dexamethasone 0.5 mg/kg ( study group ) , or no treatment ( control group ) . Pain score , emesis , oral intake and bleeding were assessed on the first and tenth postoperative day . RESULTS Overall , 204 completed the study , 101 in the study group , 103 in the control group . It was found that intraoperative single I.V. dexamethasone significantly reduces emesis during the first postoperative day ( P < 0.0001 ) , significantly reduces pain score on the first ( P < 0.0001 ) , and tenth postoperative day ( P = 0.053 ) , significantly increases the number of patients returning to soft diet on the first postoperative day ( P = 0.0002 ) and normal diet on the tenth postoperative day ( P < 0.0001 ) . No significant difference in bleeding tendency between the two groups was noted ( P = 0.7202 ) . CONCLUSIONS Intraoperative injection of I.V. dexamethasone 0.5 mg/kg effectively reduced post adenotonsillectomy morbidity OBJECTIVES /HYPOTHESIS To determine the effectiveness of dexamethasone to reduce pain after tonsillectomy in adults by at least 13 mm on the visual analogue scale . The secondary objective was to reduce the use of narcotics by at least 20 % . STUDY DESIGN This multicentric study is a prospect i ve double-blind r and omized controlled trial . METHODS A total of 102 patients were enrolled and received a 4-day trial either of dexamethasone in decreasing doses or placebo . The patients were asked to note the level of pain on the visual analogue scale daily for 7 days . They also had to record their consumption of analgesic and any eventual side effects . RESULTS There were no statistically or clinical ly significant differences between the two groups for the level of pain noted on the visual analogue scale for the first 4 and 7 days . There were no statistical differences for the consumption of hydromorphone between the two groups . CONCLUSION We can not recommend the use of dexamethasone on a routine basis following tonsillectomy in adults for the reduction of pain or narcotics consumption CONTEXT Dexamethasone is widely used to prevent postoperative nausea and vomiting ( PONV ) in pediatric tonsillectomy . OBJECTIVE To assess whether dexamethasone dose-dependently reduces the risk of PONV at 24 hours after tonsillectomy . DESIGN , SETTING , AND PATIENTS R and omized placebo-controlled trial conducted among 215 children undergoing elective tonsillectomy at a major public teaching hospital in Switzerl and from February 2005 to December 2007 . INTERVENTIONS Children were r and omly assigned to receive dexamethasone ( 0.05 , 0.15 , or 0.5 mg/kg ) or placebo intravenously after induction of anesthesia . Acetaminophen-codeine and ibuprofen were given as postoperative analgesia . Follow-up continued until the 10th postoperative day . MAIN OUTCOME MEASURES The primary end point was prevention of PONV at 24 hours ; secondary end points were decrease in the need for ibuprofen at 24 hours and evaluation of adverse effects . RESULTS At 24 hours , 24 of 54 participants who received placebo ( 44 % ; 95 % confidence interval [ CI ] , 31%-59 % ) had experienced PONV compared with 20 of 53 ( 38 % ; 95 % CI , 25%-52 % ) , 13 of 54 ( 24 % ; 95 % CI , 13%-38 % ) , and 6 of 52 ( 12 % ; 95 % CI , 4%-23 % ) who received dexamethasone at 0.05 , 0.15 , and 0.5 mg/kg , respectively ( P<.001 for linear trend ) . Children who received dexamethasone received significantly less ibuprofen . There were 26 postoperative bleeding episodes in 22 children . Two of 53 ( 4 % ; 95 % CI , 0.5%-13 % ) children who received placebo had bleeding compared with 6 of 53 ( 11 % ; 95 % CI , 4%-23 % ) , 2 of 51 ( 4 % ; 95 % CI , 0.5%-13 % ) , and 12 of 50 ( 24 % ; 95 % CI , 13%-38 % ) who received dexamethasone at 0.05 , 0.15 , and 0.5 mg/kg , respectively ( P = .003 ) . Dexamethasone , 0.5 mg/kg , was associated with the highest bleeding risk ( adjusted relative risk , 6.80 ; 95 % CI , 1.77 - 16.5 ) . Eight children had to undergo emergency reoperation because of bleeding , all of whom had received dexamethasone . The trial was stopped early for safety reasons . CONCLUSION In this study of children undergoing tonsillectomy , dexamethasone decreased the risk of PONV dose dependently but was associated with an increased risk of postoperative bleeding . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00403806 Purpose Previous studies on dexamethasone ’s antiemetic and analgesic potential in children undergoing tonsillectomy have produced conflicting results . The aim of this study was to evaluate the effects of a single dose of dexamethasone on the incidence and severity of postoperative vomiting and pain in children undergoing electrocautery tonsillectomy under st and ardized general anesthesia . Methods In a double-blinded study 120 patients were r and omly allocated to receive either dexamethasone 0.5 mg·kg−1 ( maximum dose 8 mg)iv or an equivalent volume of saline preoperatively . The incidence of early and late vomiting , need for rescue antiemetics , time to first oral intake , time to first dem and of analgesia and analgesic consumption were compared in both groups . Pain scores used included Children ’s Hospital Eastern Ontario Pain Scale , “ faces ” , and a 0–10 visual analogue pain scale . Results Compared with placebo , dexamethasone significantly decreased the incidence of early and late vomiting ( P < 0.05,P < 0.001 respectively ) . Fewer patients in the dexamethasone group needed antiemetic rescue ( P < 0.01 ) . The time to first oral intake was shorter , and the time to first dose of analgesic was longer in the dexamethasone group ( P < 0.01 ) . Pain scores 30 min after extubation were lower ( P < 0.05 ) in the dexamethasone group . At 12 and 24 hr postoperative swallowing was still significantly less painful in the dexamethasone group than in the control group ( P < 0.01 ) . Conclusion Preoperative dexamethasone 0.5 mg·kg−1iv reduced both postoperative vomiting and pain in children after electrocautery tonsillectomy . RésuméObjectifLes études antérieures sur le potentiel analgésique et antiémétique de la dexaméthasone , chez des enfants qui subissent une amygdalectomie , ont donné des résultats contradictoires . Nous voulions évaluer les effets d’une dose unique de dexaméthasone sur l’incidence et la sévérité des vomissements et de la douleur postopératoires chez des enfants qui subissent une amygdalectomie par électrocautérisation sous anesthésie générale normalisée . MéthodeDans l’étude à double insu , 120 patients ont été répartis au hasard et ont reçu , avant l’opération , soit 0,5 mg·kg−1 de dexaméthasone iv ( dose maximale de 8 mg ) , soit un volume équivalent de solution saline . L’incidence de vomissements précoces et tardifs , le besoin d’antiémétiques de secours , le temps précédant la première absorption orale et la première dem and e d’analgésie , et la consommation d’analgésique ont fait l’objet de comparaison intergroupe . Les scores de douleur utilisés comprenaient la Children ’s Eastern Ontario Pain Scale , l’échelle des “ mimiques ” et une échelle visuelle analogique cotée de 0 à 10.RésultatsComparée au placebo , la dexaméthasone a significativement réduit l’incidence de vomissements précoces et tardifs ( P < 0,05 , P < 0,001 respectivement ) . Peu de patients ayant reçu la dexaméthasone ont eu besoin d’antiémétique de secours ( P < 0,01 ) . Le temps précédant la première absorption orale a été plus court et le temps précédant la première dose d’analgésique a été plus long avec la dexaméthasone ( P < 0,01 ) . Les scores de douleur , 30 min après l’extubation , ont été plus bas ( P < 0,05 ) avec la dexaméthasone aussi . À 12 et 24 h après l’opération , la déglutition a été significativement moins douloureuse chez les enfants qui ont eu la dexaméthasone que chez les enfants témoins ( P < 0,01 ) . Conclusion Ladministration iv préopératoire de 0,5 mg·kg−1 de dexaméthasone a réduit les vomissements et la douleur postopératoires chez des enfants qui ont subi une amygdalectomie par électrocautérisation We evaluated the effect of dexamethasone on vomiting after elective tonsillectomy in 133 healthy children aged 2 - 12 yr in a r and omized , stratified , blocked , double-blind , placebo-controlled study . General anesthesia was induced by inhalation of N2 O and halothane or intravenously ( IV ) with propofol . Anesthesia was maintained with N2 O and halothane . Dexamethasone 150 micro g/kg up to a maximum dose of 8 mg , or placebo , was administered IV before surgery . All patients received 1.5 mg/kg codeine intramuscularly ( IM ) intraoperatively . Perioperative IV fluids , management of emesis , postoperative pain and hospital discharge criteria were all st and ardized . The groups were similar with respect to number , age , weight , length of surgery , and estimated intraoperative blood loss . Dexamethasone reduced the overall incidence of vomiting from 72 % ( placebo ) to 40 % ( P < 0.001 ) . Vomiting , both in-hospital and postdischarge , was decreased by the prophylactic administration of dexamethasone . Each episode of inhospital vomiting prolonged discharge by 13 + /- 2 min , mean + /- SD ( P < 0.001 ) . In conclusion , dexamethasone markedly decreased vomiting by healthy children after elective tonsillectomy in an ambulatory hospital setting . ( Anesth Analg 1996;83:913 - 6 OBJECTIVES /HYPOTHESIS To evaluate the effect of oral prednisolone on recovery from tonsillectomy . STUDY DESIGN Prospect i ve , r and omized , controlled trial of 198 consecutive patients , aged 4 years and older , with no previous or known contraindications to steroid therapy . METHODS All 198 patients scheduled for elective tonsillectomy with or without adenoidectomy from April 2013 to April 2014 were included . The participants were then r and omly assigned to receive a postoperative course of prednisolone 0.25 mg/kg/d or no prednisolone over 7 days . During the first postoperative day , pain , type of diet ( none , fluid , soft , normal ) , type of activity ( none , bed rest , quiet , restricted , normal ) , presence of nausea and vomiting , postoperative bleeding rate , and sleep disturbance were assessed using question naires . All patients were followed up on days 7 and 14 by endoscopic photographic examination of both tonsillar fossa and by completion of question naires . RESULTS No statistically significant differences in pain , diet , activity , rate of minor bleeding , nausea/vomiting , fever , or sleep disturbance were observed between the groups on day 1 . On day 7 , however , in pediatric patients , differences in pain ( P = .001 ) , diet ( P = .001 ) , activity ( P = .004 ) , mean area of re-epithelialization ( P = .000 ) , fever ( P = .04 ) , and sleep disturbance ( P = .04 ) were observed . On day 14 , differences in the mean area of re-epithelialization ( P = .000 , .001 ) remained in both pediatric and adult patients . CONCLUSIONS Oral prednisolone may be beneficial during recovery from tonsillectomy without causing any serious complications Fifty patients ( 26 males and 24 females ) who underwent tonsillectomy were then treated with injection of the long acting steroid ( Kenacort-A ) into the right tonsillar fossa after the operation . The left side was used as the control . Post-operative pain was assesed by the patients and was grade d and recorded daily as mild , moderate , and severe pain on both sides of the throat for 2 weeks . A significant reduction of pain in the tested side ( right side ) was noted in the majority of the patients . The duration of pain was shorter in the right side than the left side . It seemed to significantly reduce the post-tonsillectomy pain . Because of its simplicity , cost effectiveness , and no complications , the technique should be used for pain-free tonsillectomy in non-contraindicated cases Background Preoperative corticosteroids reduce post-tonsillectomy morbidities . The present study was performed to compare the effect of peritonsillar dexamethasone infiltration to intravenous injection together with peritonsillar levobupivacaine infiltration before tonsillectomy on postoperative pain in children . Methods One hundred twenty children , ASA I – II , aged 6–12 years , scheduled for adenotonsillectomy were enrolled in the study . They were r and omized equally into two equal groups ; 60 children each . Group A received peritonsillar infiltration with dexamethasone and levobupivacaine , and group B received i.v . dexamethasone and peritonsillar levobupivacaine infiltration . Rest and swallowing pain in the first postoperative day using a visual analogue scale , time to first rescue analgesia , cumulative paracetamol dose , vomiting , and adverse effects related to both interventions during the first postoperative day were recorded . Children care givers were asked to score pain using a verbal rating scale and to disclose complications as halitosis , headache , fever and otalgia during the first postoperative week . Results Time to first rescue analgesia was significantly longer in group A. Rest and swallowing pain in the first postoperative day , cumulative paracetamol dose , pain in the second and third postoperative days , and otalgia were significantly lower in group A. None of children developed postoperative bleeding , or complications related to dexamethasone or levobupivacaine infiltration . There was no significant difference in postoperative emesis , fever and halitosis between the groups . Conclusion Addition of dexamethasone to levobupivacaine for preoperative peritonsillar infiltration has better postoperative analgesic effects than i.v . dexamethasone combined with peritonsillar levobupivacaine infiltration in children Introduction : Surface electromyographic ( sEMG ) study of post-tonsillectomy swallow-evoked muscular reactions was performed to assess analgesic properties of dexamethasone . Methods : Sixty r and omly chosen operated adults were divided into 2 groups . Group 1 ( n = 30 ) was treated with dexamethasone ( Dexacort , 20 mg ) ; group 2 ( n = 30 ) was treated with placebo . Pain assessment included visual analogue scale ( VAS ) pain score and the EMG data such as the timing , electric amplitude and graphic patterns of muscular activity during deglutition . We investigated masseter , infrahyoid and submental-subm and ibular muscles . Records from trapezius muscle were used for control . The results were compared with previously established normative data base . The sEMG data were compared with VAS pain score with regard to changes in clinical condition of the patients . Results : Surface EMG signs of analgesia after tonsillectomy did not always correspond with the VAS pain score . Dexamethasone normalizes muscular activity in deglutition as detected by the EMG records . Statistically significant difference in muscle reactions was detected between the 2 groups . Conclusion : If dexamethasone is administered , the reduction of the postoperative pain could be secondary to the reduction of edema . The sEMG might be used for quantitative evaluation of analgesics via assessment of neuromuscular reactions to analgesia OBJECTIVE To compare the administration of bupivacaine hydrochloride , dexamethasone and lidocaine hydrochloride in decreasing post-tonsillectomy pain . METHODS Eighty patients were enrolled in the study in ENT Clinic , Firat University , and in ENT Clinic Elaziğ SSK Hospital , Elaziğ ( Turkey ) . Children between 6 and 14 years of age referred to our department for bilateral tonsillectomy for either recurrent tonsillitis or tonsillar hypertrophy . Data from 80 patients were analyzed . The first group had bupivacaine hydrochloride . The second group had dexamethasone infiltrated around each tonsil . The third group was given equal doses of 10 % lidocain hydrochloride sprayed on the tonsillectomy fossa four times a day , and a placebo group received 9 % NaCl applied to the tonsillar fossa four times a day . Pain scores , determined by visual analog scale , were obtained in the first , third and seventh postoperative days . RESULTS Pain scores in the postoperative period were identical in the first , third and seventh postoperative days . According to VAS results the groups were compared on the basis of postoperative pain . In the first postoperative day , the difference between bupivacaine-placebo , dexamethasone-placebo and lidocaine-placebo groups was found to be statistically significant ( P<0.05 ) . Nevertheless the difference between bupivacaine-dexamethasone , bupivacaine-lidocaine and dexamethasone-lidocaine were not significant ( P>0.05 ) . In the third postoperative day , the difference between bupivacaine and lidocaine group found to be statistically significant ( P<0.05 ) . In the seventh post-operative day the results of bupivacaine , dexamethasone , lidocaine and placebo groups were similar ( P>0.05 ) . CONCLUSION Bupivacaine , Dexamethasone and Lidocaine nasal aerosol decreased the pain significantly in the first postoperative day when it was compared with the placebo group . These three medicines can be used to reduce pain for children during the postoperative period applied tonsillectomy during the post-operative period . But lidocaine was more preferable , reducing pain in the third postop day better than bupivacaine OBJECTIVE To determine whether the intravenous administration of dexamethasone sodium phosphate before tonsillectomy and adenoidectomy can reduce the morbidity from , and increase the safety of , this procedure . DESIGN Prospect i ve , r and omized , double-blind , placebo-controlled clinical trial . SETTING A university medical center , caring for both ambulatory and hospitalized children . PATIENTS Eighty children aged 3 to 15 years undergoing tonsillectomy and adenoidectomy for either chronic tonsillitis or adenotonsillar hypertrophy ( obstructive sleep apnea and /or upper airway obstruction ) . INTERVENTIONS Forty-one children received intravenous dexamethasone sodium phosphate ( 1 mg/kg up to 16 mg ) and 39 received placebo before undergoing an electrocautery dissection tonsillectomy and adenoidectomy . MAIN OUTCOME MEASURES Postoperative oral intake , pain , vomiting , temperature , and complications . RESULTS Patients who received intravenous dexamethasone had significantly less trismus , vomiting , and elevations of temperature 6 hours after surgery and more oral intake ( liquids and soft solids ) at 24 hours . Three children , all of whom were in the placebo group , had emergency department visits for pain and dehydration . Each group had one child who had a secondary hemorrhage ( no surgery needed ) , one child who had pneumonia , and one child who had night terrors . CONCLUSIONS Treatment with intravenous dexamethasone before electrocautery tonsillectomy and adenoidectomy is safe , increases early postoperative oral intake , and decreases morbidity BACKGROUND Adenotonsillectomy is the most frequently performed ambulatory surgical procedure in children . Post operative agitation and inadequate pain control , for children undergoing adenotonsillectomy , can be a challenge . The aim of this study was to assess the effect of intravenous dexamethasone and oral acetaminophen codeine on emergence agitation and pain after adenotonsillectomy in children . METHODS One hundred and five pediatric patients ( 3 - 7 years old ) , scheduled to undergo adenotonsillectomy under general anesthesia , were enrolled in the study . Thirty minutes before induction , patients were r and omized to three groups . Group 1 received 0.2 mg/kg of intravenous dexamethasone and 0.25 ml/kg of oral placebo syrup . Group 2 received 20 mg/kg of oral acetaminophen codeine syrup and 0.05 ml/kg of intravenous saline . Group 3 received 0.25 ml/kg of oral placebo syrup and 0.05 ml/kg of intravenous saline . Emergence agitation and postoperative pain were assessed , recorded and compared . RESULT Agitation was less frequent in dexamethasone and acetaminophen codeine groups in comparison with placebo group , but there were not significant differences between the two groups . The pain frequencies in the three groups were not significantly different . CONCLUSION The results of this study suggest that the administration of intravenous dexamethasone ( 0.2 mg/kg ) and oral acetaminophen codeine ( 20 mg/kg ) thirty minutes before anesthesia can significantly decrease the incidence and severity of agitation but does not have an effect on postoperative pain Objective Tonsillectomy is a common procedure with a wide range of described operative techniques and usage of perioperative medications . Single-dose intraoperative dexamethasone has been shown to decrease postoperative nausea and pain and improve return to normal diet . The aim was to determine if a course of oral postoperative steroids would further decrease postoperative morbidity following tonsillectomy in children . Study Design R and omized , placebo-controlled , double-blinded trial . Power analysis recommended 198 participants . Setting A university hospital and private hospital . Subjects and Methods The authors compared a 5-day course of oral prednisolone with placebo in a pediatric population ( 3 - 16 years ) undergoing tonsillectomy to assess effects on postoperative pain , nausea , and vomiting and return to normal function . They also assessed the effect of corticosteroids on sleep duration and aspects of sleep quality . Results The results showed no significant difference between the 2 groups when analyzed for differences in the above variables both overall and at each of the postoperative 10 time points ( pain , P = .478 ; nausea and vomiting , P = .556 ; return to normal diet well , P = .234 ; return to normal activity , P = .668 ; bedtime , P = .056 ; number of times awake during the night , P = .593 ) . Conclusion There is no evidence of benefit from postoperative administration of corticosteroids in pediatric patients recovering from tonsillectomy Objective : To determine the effectiveness of dexamethasone on post tonsillectomy morbidities in patients with chronic tonsillitis . Material s and Methods : In this r and omized double-blind study , 100 patients who underwent tonsillectomy were enrolled and were r and omly allocated into control or dexamethasone group ( pre operative , intra operative and post operative groups ) . Patients were assessed for pain nausea , vomiting and oral intake in the post operative period at 24 h. Results : Patients treated with dexamethasone particularly in the pre and intra operative groups ( Group B , Group C ) showed a general trend towards lower pain score than post operative group ( Group D ) . The scores were about 1.72±0.84 and 2.20±1.19 in Groups B and C respectively , and 2.64±0.99 in Group D. Overall pain score was found to be more in the control Group A about 4.84±1.21 at 6 h post operatively and showed similar trend for next 24 h. Total number of patients with nausea was significantly high about 84 % in control group compared to dexamethasone groups ( Group B , C and D ) about 20 % , 8 % and 24 % respectively and also incidence of vomiting episodes showed a similar trend . Oral intake was significantly delayed in control group ( 6.16 ±1.52 ) , P < 0.001 than dexamethasone group . Pre operative and intra operative groups showed early intake ( 3.68±0.68 ) and ( 3.60±1.12 ) respectively than the postoperative group ( 5.08±0.95 ) . Conclusions : A single intravenous dose of dexamethasone , given following induction of anaesthesia and at the time of surgery , provided prolonged analgesia , reduced nausea and vomiting and result ed in earlier oral intake Dexamethasone effectively decreases the incidence of nausea and vomiting among pediatric and adult patients . In this study , we evaluated the effects of single-dose dexamethasone on wound healing in a prospect i ve , r and omized , experimental animal model . Anesthesia was induced with thiopental 100 mg/kg intraperitoneally . Dexamethasone 1 mg/kg was administered intraperitoneally in a dexamethasone group , and physiological saline was administered in a control group . Collagenization , epithelization , and fibroblast content were significantly less in the dexamethasone group compared with the control group ( P values of 0.002 , 0.041 , and 0.023 , respectively ) . The vascularity and the degree of inflammatory cells were more intense in the dexamethasone group compared with the control group ( P values of 0.023 and 0.002 , respectively ) . The white blood cell count was similar in the control ( 7.84 ± 2.09 ) and dexamethasone ( 6.98 ± 2.12 ) groups . The mean hydroxyproline level was 0.72 ± 0.13 mg/g in the dexamethasone and 1.03 ± 0.19 mg/g in the control group . Hydroxyproline levels were significantly less in the dexamethasone group ( P = 0.001 ) . We conclude that dexamethasone at 1 mg/kg may have negative effects on wound healing OBJECTIVES To investigate the effects of the pre-emptive local infiltration of dexamethasone vs. levobupivacaine on postoperative pain and morbidity in pediatric adenotonsillectomy patients . METHODS A total of 60 patients ( 32 males and 28 females ) , aged 3 - 14 years , were included in this double-blind prospect i ve r and omized controlled clinical study from September of 2011 until May of 2012 . Patients admitted for adenotonsillectomies after informed consent was obtained from the parents , and r and omized into three groups receiving either dexamethasone sodium phosphate ( Group 1 , mean age 5.9 ± 1.6 ) , levobupivacaine with epinephrine ( Group 2 , mean age 6.1 ± 2.6 ) , or saline ( Group 3 , mean age 6.0 ± 3.4 ) . Pain scores at the 1st , 4th , 8th , 12th , 16th , and 20th hours , and first , second , third and seventh days post-operatively were recorded by the parents using McGrath 's face scale . The operation type , operation time and anesthesia time , the time of the first request for postoperative analgesia , and the total number of analgesic interventions were recorded . RESULTS Pain scores were revealed in this order : Group 1 ( steroid ) < Group 2 ( levobupivacaine ) < Group 3 ( saline ) at all times ( p = 0.000 ) . The anesthesia times for Group 1 and Group 2 were different ( steroid vs. levobupivacaine ) , and the time to first analgesic was longer in Groups 1 ( steroid ) and 2 ( levobupivacaine ) than in Group 3 ( saline ) ( p < 0.000 ) . The total number of analgesic interventions was lower in Group 1 ( steroid ) than in Group 2 ( levobupivacaine ) and Group 3 ( saline ) ( steroid vs. saline , p = 0.000 , and steroid vs. levobupivacaine , p < 0.05 ) . CONCLUSION Peritonsillar dexamethasone infiltration was more effective than both levobupivacaine and saline in reducing post-tonsillectomy pain . It was proven to be a safe and effective method OBJECTIVE : The study goal was to determine whether the combination of dexamethasone with preemptive analgesia has an additive effect in further improving recovery . STUDY DESIGN : We conducted a prospect i ve , r and omized , double-blinded trial of 50 children undergoing tonsillectomy at a university ambulatory surgery center . One study group received 1 intravenous dose of dexamethasone , and another group received 1 dose of saline solution . All patients received tonsillar fossa injections of ropivacaine plus clonidine before tonsil excision . RESULTS : The 2 study groups were similar in main outcome measurements . Pain intensity and quality of life were not statistically different between the groups . There was a small trend to less trismus and less cumulative codeine use in the steroid group . Overall , there was a very low incidence of nausea and vomiting in both groups , which may have been due to the preemptive analgesia . CONCLUSION : Dexamethasone does not significantly improve the morbidity of pediatric tonsillectomy when preemptive analgesia with ropivacaine and clonidine is used concurrently The 5-HT3 antagonists are effective in reducing postoperative nausea and vomiting ( PONV ) associated with paediatric tonsillectomy . Although prophylactic tropisetron can reduce the incidence of PONV by half , the result ing level of over 40 % is still unacceptably high . The aim of this study was to evaluate the effect of adding dexamethasone to tropisetron . In a blinded study , 59 children ( mean age 6.1 years ) were administered 0.1 mg.kg-1 up to 2 mg of tropisetron and 66 children ( mean age 5.7 years ) received the same dose of tropisetron plus 0.5 mg.kg-1 up to 8 mg of dexamethasone . Both drugs were given intravenously during induction of anaesthesia for tonsillectomy . During the inpatient stay of 24 h , the incidence of postoperative vomiting in the tropisetron alone group was 53 % compared with 26 % in the combination group ( P=0.002 , chi-squared ) . A significant reduction in nausea from 53 % to 30 % was also observed ( P=0.02 ) . Parents completed a daily diary for 5 days following discharge . Delayed vomiting occurred in 27 % and 11 % of the tropisetron and combination therapy groups , respectively ( P=0.025 ) Sixteen percent and 9 % , respectively , required medical attention ( P=0.27 ) . Tropisetron plus dexamethasone is more effective than tropisetron alone in reducing the incidence of PONV following paediatric tonsillectomy UNLABELLED In this double-blinded , r and omized , placebo-controlled study , we assessed the effect of dexamethasone 0.5 mg/kg IV administered preoperatively in 110 children 2 - 12 yr old , undergoing electrodissection adenotonsillectomy , using a st and ardized anesthetic technique . The incidence of early and late vomiting , the time to first oral intake , the quality of oral intake , the satisfaction scores , and the duration of IV hydration were compared in both groups . The overall incidence of vomiting , as well as the incidence of late vomiting , was significantly less in the Dexamethasone group as compared with the Saline group ( 23 % and 19 % vs 51 % and 34 % , respectively ) . The time to first oral intake and the duration of IV hydration were shorter in the Dexamethasone group compared with the Saline group ( P < 0.05 ) . The quality of oral intake and the satisfaction scores were better in the Dexamethasone group than in the Saline group ( P < 0.05 ) . This report confirms the beneficial effect of IV dexamethasone on both vomiting and oral intake in children undergoing electrodissection adenotonsillectomy . IMPLICATION S In this double-blinded , placebo-controlled study , we examined the efficacy of a single dose of dexamethasone 0.5 mg/kg IV on posttonsillectomy vomiting and oral intake in children 2 - 12 yr old . Dexamethasone significantly decreased the incidence of postoperative vomiting during the first 24 h , shortened the time to the first oral intake and the duration of IV hydration , and improved the quality of oral intake and the satisfaction scores of the patients A prospect i ve , r and omized , double-blind , placebo-control clinical study was performed to determine the effects of peritonsillar infiltration of dexamethasone on peroperative and postoperative morbidity in patients undergoing tonsillectomy with local anesthesia . A total of fifty-two patients , aged 14 - 34 , were r and omized to infiltrate dexamethasone ( 0.5 mg/kg , maximum dose , 12 mg ) or placebo with local anesthetic at the peritonsillar region . Incidence of postoperative complications , pain medications , appetite , oral intake ( type of diet ) and fever were also compared between the two groups . Demographics of dexamethasone and placebo groups were similar . No statistically significant differences were noted peroperative procedures , postoperative complications , pain medication , appetite , oral intake ( type of diet ) between the two groups of patients BACKGROUND The aim of the present study is to evaluate the effect of preoperative 0.5 mg/kg i.v . dexamethasone in combination with 0.5 mg/kg i.v . ketamine on pain , early oral intake and vomiting in pediatric patients undergoing tonsillectomy during the first 24 hours of the postoperative period . METHODS One hundred twenty children who were scheduled for tonsillectomy were r and omly assigned to receive a single dose of dexamethasone 0.5 mg/kg i.v . as Group D ( n = 30 ) , receive ketamine 0.5 mg/kg i.v . as Group K ( n = 30 ) , receive dexamethasone 0.5 mg/kg i.v . and ketamine 0.5 mg/kg i.v . as Group KD ( n = 30 ) and an equivalent volume of saline as Group C ( n = 30 ) 15 minutes before the induction of anesthesia . Post-operative pain was evaluated using an observational pain score ( OPS ) on arrival to the post-anesthesia care unit ( PACU ) , at 15 , 30 , 45 , and 60 minutes after that and at 1 , 2 , 4 , 6 , 12 , and 24 hours after arrival to the ward . RESULTS OPS scores were significantly lower at the time of arrival to the PACU , and at 15 , 30 , 45 , and 60 minutes in the Group KD compared with Group C ( p < 0.05 ) . Postoperative OPS scores were significantly lower at 1 , 2 , 4 , 6 , 12 , and 24 hours after operation in Group KD compared with Group C ( p < 0.05 ) . CONCLUSION A prophylactic preoperative single dose of i.v . 0.5 mg/kg dexamethasone in combination with a single dose of i.v . 0.5 mg/kg ketamine significantly decreased post-tonsillectomy pain compare with using i.v . ketamine or i.v . dexamehasone separately Background and Objective : Recently , dexamethasone has been found to have a prophylactic effect on postoperative vomiting and pain in children undergoing tonsillectomy . However , few studies have examined the preemptive analgesic effects of dexamethasone after tonsillectomy . The aim of this study was to evaluate the effect of pre-incisional infiltration of tonsils with dexamethasone on the incidence and severity of postoperative pain and vomiting in children undergoing tonsillectomy under general anesthesia . Material s and Methods : In a double blinded study , 62 patients were r and omly allocated to infiltrate dexamethasone ( 0.5 mg/kg , maximum dose , 12 mg ) or an equivalent volume of saline at the peritonsillar region . All infiltrations were performed following the induction of general anesthesia and 5 minutes prior to the onset of surgery . Anesthetic agents , end-tidal carbon dioxide levels , and the administration of intravenous fluids were carefully regulated . Surgery was performed by one attending otolaryngologists using the same dissection and snare technique . The incidence of pain and vomiting , need for rescue antiemetics , and analgesic consumption were compared in both groups . Pain scores used included Children 's Hospital Eastern Ontario Pain Scale , “ faces ” , and a 0 - 10 visual analogue pain scale . Results : Demographics of dexamethasone and placebo groups were similar . No statistically significant difference was found between the dexamethasone and placebo groups in pain score , nausea , vomiting , irritability , or analgesic requirement postoperatively . Conclusion : Preincisional infiltration of the tonsils with dexamethasone play a limited role in the recovery phase from tonsillectomy , but further prospect i ve , r and omized studies are needed to support it PURPOSE The purpose of this study was to evaluate the effect of submucosal administration of dexamethasone sodium phosphate on discomfort after m and ibular third molar surgery . PATIENTS AND METHODS Sixty-one consecutive patients requiring surgical removal of a single m and ibular impacted third molar under local anesthesia were r and omly placed into 3 groups . After the onset of local anesthesia , the experimental groups received dexamethasone at 2 different doses ( 4 or 8 mg ) as submucosal injection , and the control group received no drug . St and ardized surgical and analgesic protocol s were followed . Maximum interincisal distance and facial contours were measured at baseline and at postsurgery days 2 and 7 . Pain was objective ly measured by counting the number of analgesic tablets required . The patients ' perception of the severity of symptoms was assessed with a follow-up question naire ( PoSSe scale ) . RESULTS On the second postoperative day , facial edema showed a statistically significant reduction in both dexamethasone 4-mg and dexamethasone 8-mg groups compared with the control group , but no statistically significant differences were observed between the 2 dosage regimens of dexamethasone . By contrast , there was no statistically significant difference between all groups when postoperative swelling was evaluated at day 7 ( P > .50 ) . The treatment group had a limited and nonsignificant effect on pain and trismus when compared with the control group at the 2 times of evaluation . CONCLUSIONS Parenteral use of dexamethasone 4 mg , given as an intraoral injection at the time of surgery , is effective in the prevention of postoperative edema . Increasing the dose to 8 mg provides no further benefit The aim of this study was to assess the effect of a course of dexamethasone on postoperative pain and morbidity after adult tonsillectomy . We report the results of a double-blind , r and omized , placebo-controlled trial of 200 adult patients undergoing elective tonsillectomy . Patients were r and omized to three groups : one group received the non-steroidal anti-inflammatory drug piroxicam for 8 days postoperatively , one group received dexamethasone for the same period and the third group received both drugs . Patients recorded their pain scores and analgesic requirements daily for 10 days . Patients treated with a combination of piroxicam and dexamethasone recorded consistently lower pain scores than those treated with either drug alone . This difference was statistically significant ( P < 0.05 ) on all days except the day of surgery and the second postoperative day . Patients treated with piroxicam alone had significantly higher analgesic requirements than in either of the other groups . Dexamethasone given in this regime reduces postoperative pain and analgesic requirements after adult tonsillectomy OBJECTIVE To compare the effect of ropivacaine plus dexamethasone and ropivacaine alone as infiltration anesthesia on postoperative pain , nausea and vomiting , and oral intake in children after tonsillectomy and adenoidectomy . METHODS Two hundred pediatric patients scheduled for tonsillectomy and adenoidectomy were prospect ively enrolled and r and omly placed in a ropivacaine with dexamethasone group ( RD ) or a ropivacaine alone group ( R ) . Treatment for both groups was administered by local infiltration , and pain scores were recorded at various intervals . Primary outcomes were pain scores recorded 4 - 24h postoperation . Secondary outcomes included time to the first administration of analgesic and total consumption of analgesics for all children , time to first water request , first oral intake , incidence of nausea or vomiting , and time to discharge . RESULTS From postoperative hours 4 - 24 , children in the RD group had lower pain scores than children in the R group ( P < 0.05 ) . Total fentanyl consumption was significantly decreased in the RD group compared to the R group ( 50.9 ± 9.3 vs. 103.9 ± 11.5 μg , P < 0.001 ) . The time to first water request and first oral intake were significantly shorter in the RD group [ ( 40 min ( 27 - 64 ) vs. 64 min ( 43 - 89 ) ; P < 0.001 ) and ( 54 min ( 40 - 91 ) vs. 85 min ( 67 - 127 ) ; P < 0.001 ) , respectively ] . Oral intake was significantly improved , and the incidence of nausea and vomiting were reduced in the RD group ( P < 0.05 ) . The time to discharge was shorter in the RD group when compared with the R group ( 9.06 ± 0.89 d vs. 7.05 ± 0.71 d ; P < 0.001 ) . CONCLUSIONS Ropivacaine plus dexamethasone infiltration effectively lowers pain , improves oral intake , lowers postoperative nausea and vomiting , and decreases the time to discharge OBJECTIVE Postoperative morbidity in patients undergoing tonsillectomy with or without adenoidectomy includes inadequate oral intake , pain , nausea , vomiting and bleeding . The purpose of this study is to evaluate the effect of preoperative 0.5 mg/kg i.v . dexamethasone on postoperative early oral intake , pain , vomiting in patients undergoing adenotonsillectomy while performing st and ard anesthesia technique and sharp dissection tonsillectomy . METHODS In this prospect i ve , double-blinded , placebo-controlled study 62 children , aged 4 - 12 years , who underwent tonsillectomy with or without adenoidectomy were r and omly assigned to receive single dose of 0.5 mg/kg i.v . dexamethasone preoperatively . Patients started to receive 100 ml of clear fluids 2 h postoperatively , then were offered every hour . When pain score was 3 or above , paracetamol was given for pain control . Tolerating 400 ml of clear fluids , no bleeding and no vomiting were accepted as discharge criteria . The discharge time was also recorded . The incidence of early vomiting , pain scores , amount of oral intake were recorded until the discharge time . RESULTS Compared with placebo , the patients who received preoperative dexamethasone had significantly less pain score during the first 6 h postoperatively ( p<0.05 ) , adequate amount of oral intake time was shorter ( p<0.05 ) and the discharge time was earlier ( p<0.05 ) . No difference was found in vomiting incidence in both groups . CONCLUSION Preoperative dexamethasone use significantly reduces early posttonsillectomy pain , improves oral intake and facilitates meeting the discharge criteria while using st and ard anesthesia technique and sharp dissection tonsillectomy without any significant side effects A prospect i ve r and omized controlled study was conducted in 50 patients evaluating the effect of single intra - operative intravenous dose of dexamethasone on post — operative morbidity . Dexamethasone was found to significantly reduce the incidence of vomiting in 1st 24 hrs , trismus . pain , time for 1st solid intake , need to administer rescue analgesic and fever . Besides the number of school days lost in study group were less compared to control due to earlier feeling of well being OBJECTIVE Our objective is to determine the optimum dosage of intraoperative single dose dexamethasone and its effect upon postoperative morbidity in pediatric tonsillectomy and adenotonsillectomy patients . STUDY DESIGN AND METHODS Totally 150 pediatric patients whom underwent adenotonsillectomy or tonsillectomy surgery are offered to participate in this study at otorhinolaryngology clinic between 2002 and 2003 . 150 patients are divided into three r and omized groups , each composed of fifty patients . Anesthesia protocol is st and ardized in each group and 0.2 mg/kg intraoperative dexamethasone is given to first group , 0.7 mg/kg ( maximum dose 25 mg ) intraoperative dexamethasone is given to second group and third group is accepted as control group without giving any intravenous dexamethasone . Each group is compared for postoperative nausea , vomiting and tolerability to take oral foods within first 24h with the same question naire . RESULTS There is significantly higher ratio of postoperative nausea and vomiting within first 24h in group III ( 80 % ) when compared with group I ( 8 % ) ( p : 0.001 ; p<0.01 ) and group II ( 4 % ) ( p : 0.001 ; p<0.01 ) . Also there is significantly higher ratio of patient 's tolerability to take oral semisolid/solid foods within postoperative first 24h in group II ( 94 % ) when compared with group I ( 58 % ) ( p : 0.001 ; p<0.01 ) and group III ( 12 % ) ( p : 0.001 ; p<0.01 ) . We did n't encounter any side effect of dexamethasone in group I and II . CONCLUSIONS We thought that 0.7 mg/kg dosage of IV dexamethasone is much a preferable choice depending of its effectiveness on decreasing postoperative morbidity rather than 0.2 mg/kg dosage and beside to this advantage we did n't encounter any side effects OBJECTIVE The purpose of this study is to determine whether a single dose of dexamethasone 0.5mg/kg administered before surgery could decrease post operative vomiting and pain and improves oral intake in the first 24-hours after pediatric tonsillectomy procedures . METHODS It is a r and omized , double blind , placebo controlled study . Sixty children age 2 - 12-years ASA 1 and 11 were scheduled for tonsillectomy , dexamethasone ( n=29 ) and control group ( n=31 ) were enrolled in the study . Dexamethasone group received 0.5mg/kg intravenous dexamethasone and control group received saline at the time of induction . The anesthetic regimen and surgical procedures were st and ardized for all patients . All patients were observed in post anesthesia care unit ( PACU ) and ward for post operative vomiting , pain , need for rescue antiemetic or analgesia and time for first oral intake for 24-hours . RESULTS Data from 60 patients were analyzed . The overall incidence of early as well as late vomiting was significantly less in dexamethasone as compared to control group ( 37 % versus 74 % P=0.016 ) , overall incidence of retching was 29 % in control and 3.4 % in dexamethasone ( p=0.008 ) . Vomiting once or more than once was significantly high in control as compared to dexamethasone group . The need for rescue antiemetic , the time to first oral intake and analgesic requirements did not show any significant difference in both groups . CONCLUSION Dexamethasone is considered safe and there was no adverse effects associated with a single dose of dexamethasone . Although the need for rescue antiemetic , time to oral intake and analgesia requirements in both groups were not significant , however , we found that dexamethasone does have antiemetic properties as overall incidence of retching and vomiting was significantly less in dexamethasone group as compared to control group in children who underwent tonsillectomy A prospect i ve , r and omized , double-blind study to assess the effect of steroids on post-tonsillectomy pain was performed on 82 adults . The premedication , anaesthesia , surgical technique and post-operative analgesia were st and ardized . Pain was assessed on a visual analog scale . Steroids were found to have no appreciable effect on the amount of post-operative pain A prospect i ve , r and omized , double-blind study to determine the postoperative effects of steroids in tonsillectomy was performed on 25 children from 4 to 12 years of age . A single intravenous dose of dexamethasone or a placebo was administered at onset of surgery . Other preoperative and postoperative medications , including antibiotics , anesthesia , and surgical techniques were st and ardized as noted in this article . The ability to return to a full or semifull diet occurred on the third and fourth postoperative days , significantly sooner in the steroid-treated patients than in the control patients . By the fifth and sixth days , the control group were eating as well as those children who received steroids . No significant differences were observed in postoperative pain , nausea , emesis , fever , or in the need for postoperative pain medications . This preliminary article concludes that a single preoperative dose of steroid results in an earlier return to a normal ( full ) diet in children who had undergone tonsillectomy OBJECTIVES To investigate the role of a 7-day course of oral prednisolone on recovery from tonsillectomy . STUDY DESIGN Double-blind , r and omized , placebo-controlled trial of 50 consecutive patients , aged 5 years and older , who had no previous or known contraindications to steroid therapy . METHODS The patients were r and omized at the time of surgery to either a 7-day course of daily placebo or prednisolone ( dosage : 10 mg per day in patients aged 5 - 11 y , 0.5 mg/kg in those aged 12 and older ) . Age , sex , weight , diagnosis , tonsil size ( in cm2 ) , additional adenoidectomy , performing surgeon , method of dissection , length of procedure , total blood loss , intraoperative fluid requirement , and length of hospitalization were documented for each patient . During the first postoperative day , morning pain score , paracetamol use , oral fluid intake , temperature , presence of nausea and vomiting , level of activity ( low , moderate , or normal ) , and type of diet ( liquid , soft , or normal ) were recorded . RESULTS The steroid group consisted of a greater number of diathermy dissection cases and had significantly less intraoperative blood loss ( P value = .022 and .017 , respectively ) . On postoperative days 4 to 7 , the steroid group experienced less nausea and vomiting ( P value = .01 , .04 , .04 , and .04 , respectively ) . Paracetamol use was less in the steroid group on days 2 , 7 , and 8 ( P value = .03 , .02 , and .02 , respectively ) . There was no difference between the two groups for the other data measured . CONCLUSION A 7-day course of corticosteroids may play a limited role in patients ' recovery from tonsillectomy There are numerous studies using various agents to reduce posttonsillectomy morbidity . Due to lack of conclusive results a double-blind study using methylprednisolone acetate ( Depo Medrol ) was conducted . A total of 165 patients were r and omly divided into two groups . Following tonsillectomy 2.5 ml of solution was injected into the base of each tonsillar fossa . The study group received 20 mg of deposteroid to each fossa while the control group got normal saline . The deposteroid reduced postoperative pain but did not significantly alter other factors contributing to morbidity such as difficulty in swallowing or resumption of a normal diet . The deposteroid appeared to have no effect on the rate of healing of the tonsillar fossa Background Post-operative morbidity following tonsillectomy remains an important clinical problem despite advances in anesthetic and surgical techniques . This study investigated the effect of a one-day course of intravenous dexamethasone on recovery from tonsillectomy . Patients and Methods In a double-blind , r and omized , placebo-controlled trial , 30 consecutive adult patients between 18 and 35 years of age , who had no previous or known contraindications to steroid therapy , were r and omly assigned at the time of surgery to either a 24-hour course of dexamethasone ( 3 doses of 6 mg IV ) or placebo with the first dose administered during surgery , and subsequent doses given after 8 and 16 hours . The same surgeon treated all patients . Postoperative signs and symptoms , including pain , nausea , vomiting , progress of healing and the degree of granulation , were evaluated for 2 weeks . Results Patients treated with dexamethasone showed significantly less pain , nausea and vomiting , better healing and less granulation . There were no side effects reported . Conclusion Application of 3 doses of dexamethasone within 24 hours during and after tonsillectomy is advisable because of the reduction of postoperative morbidity , especially pain and edema Objective To compare local infiltration of dexamethasone to intravenous injection for postoperative pain and recovery after tonsillectomy . Study Design Prospect i ve , r and omized study . Setting Second Affiliated Hospital of Harbin Medical University . Subjects and Methods Children ( n = 240 , American Society of Anesthesiologists [ ASA ] classes I-II , aged 5 - 10 y ) scheduled for tonsillectomy were r and omly and equally assigned to 3 groups : DEX-IV , for intravenous injection of dexamethasone ( 0.5 mg/kg , maximum dose 24 mg ) ; DEX-INF , given the same amount of dexamethasone by local infiltration to the upper middle and lower poles of the tonsils ; and a control group not given dexamethasone . Postoperative pain was scored at intervals from 30 minutes to 24 hours . The time to first administration of analgesic and average consumption of analgesic , times to first oral water and solid food intake , and incidence rates of nausea and vomiting were evaluated . Results From postoperative 1 to 16 hours , the DEX-INF group had significantly lower pain scores than did the DEX-IV group , and the time to first analgesic and average consumption of analgesic were also significantly lower . The times to first oral water and food intake in the DEX-INF group were significantly shorter than in the DEX-IV group . The incidence of nausea and vomiting in the DEX-INF group was higher than that of the DEX-IV group . Conclusion Local infiltration of dexamethasone was more effective than systemic administration to decrease pain and time to food intake , but the antiemetic effect was less . Clinical trials registration number : ChiCTR-TRC-13003535 Background : Different methods and many drugs have been used to control the post-operative pain . In this study , we evaluate the role of gabapentin premedication and /or dexamethasone in management of post-operative pain following adenotonsillectomy in children . Material s and Methods : In a double-blind r and omized study , 120 children were subjected for adenotonsillectomy classified into three equal groups . Group G : Gabapentin 10 mg/kg was given orally 2 h before induction of anesthesia ( Gabapentin syrup 250 mg/5 ml . Group D : Children in this group received placebo pre-operatively and received dexamethasone 0.15 mg/kg intravenously after induction of anesthesia , but before surgery . Group C : Children in this group received combination of oral gabapentin 10 mg/kg 2 h before induction of anesthesia and intra-operative 0.15 mg/kg dexamethasone intravenously . All children underwent general anesthesia . Pain score was assisted post-operatively 2 h , 4 h , 6 h , 8 h , 12 h and 18 h after recovery using face , legs , activity , cry , consolability scale . Results : Pain score in Group C and Group G was significantly less at 4 h , 6 h and 8 h post-operatively than in Group D ( P < 0.05 ) . At 12 h , the pain score in Group C was significantly less than Group G and Group D ( P < 0.05 ) . And no significant changes were observed in pain score at 18 h post-operatively between all groups ( P > 0.05 ) . The time to first analgesia was longer in the Group C than in Group G and Group D and the time to first analgesia was significantly longer in Group G than in Group D ( P < 0.05 ) . The total amount of pethidine was less in Group C and Group G than in Group D ( P < 0.05 ) . The incidence of post-operative nausea and vomiting was statically insignificant among all groups and no reported post-operative bleeding . Conclusion : Gabapentin 10 mg/kg premedication combined with intra-operative dexamethasone 0.15 mg/kg prolongs the post-operative analgesia following adenotonsillectomy in children and decreases the amount of pethidine used post-operatively with no reported adverse effects or increase in the incidence of post-operative bleeding |
12,854 | 25,229,835 | Adverse events were more frequent in participants receiving opioids compared with control .
The small mean benefit of non-tramadol opioids are contrasted by significant increases in the risk of adverse events . | BACKGROUND Osteoarthritis is the most common form of joint disease and the leading cause of pain and physical disability in older people .
Opioids may be a viable treatment option if people have severe pain or if other analgesics are contraindicated .
However , the evidence about their effectiveness and safety is contradictory .
This is an up date of a Cochrane review first published in 2009 .
OBJECTIVES To determine the effects on pain , function , safety , and addiction of oral or transdermal opioids compared with placebo or no intervention in people with knee or hip osteoarthritis . | BACKGROUND Glucosamine and chondroitin sulfate are used to treat osteoarthritis . The multicenter , double-blind , placebo- and celecoxib-controlled Glucosamine/chondroitin Arthritis Intervention Trial ( GAIT ) evaluated their efficacy and safety as a treatment for knee pain from osteoarthritis . METHODS We r and omly assigned 1583 patients with symptomatic knee osteoarthritis to receive 1500 mg of glucosamine daily , 1200 mg of chondroitin sulfate daily , both glucosamine and chondroitin sulfate , 200 mg of celecoxib daily , or placebo for 24 weeks . Up to 4000 mg of acetaminophen daily was allowed as rescue analgesia . Assignment was stratified according to the severity of knee pain ( mild [ N=1229 ] vs. moderate to severe [ N=354 ] ) . The primary outcome measure was a 20 percent decrease in knee pain from baseline to week 24 . RESULTS The mean age of the patients was 59 years , and 64 percent were women . Overall , glucosamine and chondroitin sulfate were not significantly better than placebo in reducing knee pain by 20 percent . As compared with the rate of response to placebo ( 60.1 percent ) , the rate of response to glucosamine was 3.9 percentage points higher ( P=0.30 ) , the rate of response to chondroitin sulfate was 5.3 percentage points higher ( P=0.17 ) , and the rate of response to combined treatment was 6.5 percentage points higher ( P=0.09 ) . The rate of response in the celecoxib control group was 10.0 percentage points higher than that in the placebo control group ( P=0.008 ) . For patients with moderate-to-severe pain at baseline , the rate of response was significantly higher with combined therapy than with placebo ( 79.2 percent vs. 54.3 percent , P=0.002 ) . Adverse events were mild , infrequent , and evenly distributed among the groups . CONCLUSIONS Glucosamine and chondroitin sulfate alone or in combination did not reduce pain effectively in the overall group of patients with osteoarthritis of the knee . Exploratory analyses suggest that the combination of glucosamine and chondroitin sulfate may be effective in the subgroup of patients with moderate-to-severe knee pain . ( Clinical Trials.gov number , NCT00032890 . ) Background The heterogeneity statistic I2 , interpreted as the percentage of variability due to heterogeneity between studies rather than sampling error , depends on precision , that is , the size of the studies included . Methods Based on a real meta- analysis , we simulate artificially ' inflating ' the sample size under the r and om effects model . For a given inflation factor M = 1 , 2 , 3 , ... and for each trial i , we create a M-inflated trial by drawing a treatment effect estimate from the r and om effects model , using si2MathType@MTEF@5@5@+=feaagaart1ev2aaatCvAUfKttLearuWrP9MDH5MBPbIqV92AaeXatLxBI9gBaebbnrfifHhDYfgasaacPC6xNi = xH8viVGI8Gi = hEeeu0xXdbba9frFj0xb9qqpG0dXdb9aspeI8k8fiI+fsY = rqGqVepae9pg0db9vqaiVgFr0xfr = xfr = xc9adbaqaaeGaciGaaiaabeqaaeqabiWaaaGcbaGaem4Cam3aa0baaSqaaiabdMgaPbqaaiabikdaYaaaaaa@2FBE@/M as within-trial sampling variance . Results As precision increases , while estimates of the heterogeneity variance τ2 remain unchanged on average , estimates of I2 increase rapidly to nearly 100 % . A similar phenomenon is apparent in a sample of 157 meta-analyses . Conclusion When deciding whether or not to pool treatment estimates in a meta- analysis , the yard-stick should be the clinical relevance of any heterogeneity present . τ2 , rather than I2 , is the appropriate measure for this purpose OBJECTIVE This study compared the efficacy and tolerability of a once-daily controlled-release formulation of hydromorphone ( OROS ) hydromorphone , Janssen-Cilag , Beerse , Belgium ) and twice-daily extended-release ( ER ) oxycodone in patients with chronic , moderate to severe osteoarthritis ( OA ) pain . OROS hydromorphone is currently available only in Europe . METHODS Adults who met American College of Rheumatology clinical criteria for OA of the knee or hip with moderate to severe mean daily pain intensity despite chronic use of stable doses of NSAIDs or other nonsteroidal , nonopioid therapies were eligible for participation in this r and omized , open-label study . The study consisted of a 14-day dose-titration and stabilization phase and a 28-day maintenance phase . OROS hydromorphone and ER oxycodone were initiated at dosages of 8 mg QD and 10 mg BID , respectively . Patients maintained diaries in which they rated their pain ( from 0 = none to 3 = severe ) and pain relief ( from 0 = no relief to 4 = complete relief ) . Other assessment s completed every 14 days included patient and investigator global evaluations of treatment effectiveness ( scale from 1 = poor to 5 = excellent ) , the Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index , and the Medical Outcomes Study ( MOS ) Sleep Scale . Adverse events ( whether observed by study personnel , identified in response to question ing , or spontaneously reported ) and vital signs were monitored throughout the study . The primary efficacy measures were the mean pain relief score at end point and the time from initiation of treatment to the third day of moderate to complete pain relief , as reported in the patient diary . Noninferiority analyses were conducted on all primary and secondary efficacy variables . RESULTS One hundred thirty-eight patients ( 71 OROS hydromorphone , 67 ER oxycodone ) received treatment ( safety population ) , and 83 ( 60.1 % ) completed the study . Data from 124 patients were included in the efficacy analyses ; the majority of these patients were white ( 85.5 % ) and female ( 69.4 % ) , with a mean age of 63.6 years . The most commonly affected joint was the knee ( 79.8 % ) . At end point , the OROS hydromorphone group had a mean pain relief score of 2.3 ( median , 2.0 ) and the ER oxycodone group had a mean pain relief score of 2.3 ( median , 2.3 ) ( 95 % CI , -0.30 to infinity ) . The mean time to the third day of moderate to complete pain relief was 6.2 days ( median , 4.0 ) in the OROS hydromorphone group and 5.5 days ( median , 5.0 ) in the ER oxycodone group ( 95 % CI , -0.31 to infinity ) . Mean pain intensity decreased from baseline to end point by 0.6 point in the OROS hydromorphone group and by 0.4 point in the ER oxycodone group . Mean scores on the patient global evaluation improved by a respective 1.2 and 1.0 points ( median , 1 in both groups ) . Approximately two thirds of patients in each group ( 67.2 % and 66.7 % ) rated the overall effectiveness of treatment as good to excellent at end point . There were no statistically significant differences between groups in total WOMAC scores at end point , and similar improvements from baseline in the WOMAC physical function , stiffness , and pain scales were observed in both groups . Whereas MOS sleep outcomes scores improved from baseline in both groups , OROS hydromorphone was associated with a significantly greater improvement on the MOS Sleep Problems Index I compared with ER oxycodone ( P < 0.045 ) . Adverse events were comparable in both groups ; the most frequently reported adverse events were nausea ( 35.2 % and 29.9 % ) , constipation ( 29.6 % and 25.4 % ) , somnolence ( 25.4 % and 17.9 % ) , vomiting ( 16.9 % and 11.9 % ) , and dizziness ( 14.1 % and 22.4 % ) . Adverse events led to study discontinuation in 35.2 % ( 25/71 ) of patients in the OROS hydromorphone group and 32.8 % ( 22/67 ) in the ER oxycodone group . Discontinuations due to adverse events during the titration phase were numerically greater in the OROS hydromorphone group ( 29.6 % [ 21/71 ] ) than in the ER oxycodone group ( 19.4 % [ 13/67 ] ) . Only 1 serious adverse event ( diarrhea in a patient receiving OROS hydromorphone ) was considered possibly related to study drug . CONCLUSIONS Once-daily OROS hydromorphone and twice-daily ER oxycodone provided similar pain relief in these patients with OA of the knee or hip . The tolerability profiles of the 2 agents were similar We aim ed to evaluate the efficacy and safety of oxycodone/acetaminophen ( O/A ) and codeine/acetaminophen ( C/A ) vs. conventional therapy ( CT ) without opioids in older women suffering from osteoarthritis (OA)-related pain , sub-optimally responsive to prior conventional treatments . We performed a 6 week , r and omized , single blind , controlled study in three nursing homes . We enrolled 154 women with painful OA . They were assigned to treatment with O/A ( n=52 ) and C/A ( n=52 ) vs. CT ( n=50 ) . We evaluated at baseline and at week 6 : average pain in the last week ( mean pain , MeP ) , pain at rest ( RP ) , pain in movement ( MP ) ( numeric rating scale , NRS ) ; depressive symptoms ( Beck Depression Inventory-II , BDI-II ) ; functional status ( activities of daily living , ADL ) and cognitive status ( mini mental state evaluation , MMSE ) . We considered the adverse events ( AEs ) in the study period . At week 6 , MeP , RP and MP were significantly reduced in all three groups ( p<0.001 ) ; compared to CT , O/A and C/A were associated with greater reductions in MeP ( p<0.001 and p=0.004 , respectively ) , in RP ( p=0.028 and p=0.032 , respectively ) in MP ( p<0.001 and p=0.002 , respectively ) and with significant improvement in BDI-II score ( p=0.05 and p=0.04 , respectively ) and ADL value ( p=0.04 and p=0.05 , respectively ) . AE rates did not differ between groups OBJECTIVE Evaluate the long-term safety , tolerability , and efficacy of Remoxy ® ( extended-release oxycodone ) in patients with chronic pain related to osteoarthritis of the hip and /or knee or chronic low back pain . DESIGN Open-label , 12-month , phase 3 trial . SETTING Fifty-nine US sites . PATIENTS Men and women with moderate to severe hip and /or knee pain caused by osteoarthritis or persistent moderate to severe low back pain . INTERVENTION Remoxy 5 mg twice daily , which could be increased in fixed increments up to 80 mg twice daily . OUTCOME MEASURES Safety and tolerability assessment s included adverse events ( AEs ) , laboratory tests , vital signs , physical examinations , and electrocardiograms . Efficacy was assessed through ratings of pain intensity , quality of analgesia , and global assessment of study drug . RESULTS Of the 828 patients enrolled , 823 received ≥1 dose of Remoxy , with 469 exposed for ≥180 days and 381 for ≥358 days . At least one AE was experienced by 678 patients ( 82 % ) , the most common of which were opioid related , including constipation , nausea , and somnolence ; 173 patients ( 21 % ) discontinued treatment because of AEs . No clinical ly relevant changes were seen in other safety assessment s. Mean pain intensity scores decreased significantly from baseline at all time points ( P < 0.001 ) . At month 12 , quality of analgesia and global assessment of study drug were rated positively ( good , very good , or excellent ) by 64 % and 61 % of patients ( last observation carried forward ) , respectively . CONCLUSIONS Long-term treatment with Remoxy was safe , well tolerated , and efficacious in patients with chronic pain related to osteoarthritis of the hip and /or knee or chronic low back pain UNLABELLED ALO-01 ( EMBEDA [ morphine sulfate and naltrexone hydrochloride ] extended-release capsules [ King Pharmaceuticals , Inc , Bridgewater , NJ ] ) , indicated for chronic moderate-to-severe pain , is design ed to release naltrexone upon tampering ( eg , by crushing ) , reducing morphine-induced subjective effects . This multicenter , r and omized , double-blind , crossover study assessed pharmacokinetics , efficacy , and safety of ALO-01 and compared them with extended-release morphine sulfate ( ERMS , KADIAN [ morphine sulfate extended-release ] capsules [ Actavis US , Morristown , NJ ] ) in adults ( N = 113 ) with osteoarthritis pain . Study periods included washout until pain flare ( intensity > or = 5 , 0 to 10 ; 0 = no pain , 10 = worst pain ) ; dose titration with ERMS ( 20 to 160 mg BID ) ; and r and omization to 2 ( crossover ) 14-day treatment periods with ERMS or ALO-01 , separated by 7 days of open-label ERMS . Assessment s included pharmacokinetics ( morphine , naltrexone ) , pain scores ( 0 to 10 ) , Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index ; Patient Global Assessment of Medication ( 1 to 5 ; poor to excellent ) . Mean score at pain flare was 7.1 . Morphine exposure from both formulations at steady state was similar . Plasma naltrexone concentrations were below limit-of-quantification for most patients and , when present , did not impact pain scores . During treatment , mean pain intensity ( day 14 : ERMS , 2.4 ; ALO-01 , 2.3 , P = .31 ) , WOMAC change-from-baseline ( mean pain , physical function , composite scores ) , and adverse event frequency were similar . ALO-01 and ERMS provided similar relief of osteoarthritis pain . PERSPECTIVE We present data demonstrating that ALO-01 has steady-state morphine exposure , efficacy , and safety similar to marketed ERMS capsules . Results highlight the potential for morphine in ALO-01 to manage moderate-to-severe osteoarthritis pain , while the sequestered naltrexone does not interfere with efficacy OBJECTIVE Pain is the cardinal feature of osteoarthritis ( OA ) , and with advancing disease there is loss of function and increasing pain even at times of joint rest . Few studies have evaluated the role of opioid analgesics in treating the pain of OA . METHODS This r and omized , double blind , parallel group study compared the efficacy and safety of a 12 hourly controlled release codeine formulation ( Codeine Contin ) with placebo in patients with chronic pain due to OA of the hips and /or knees . The 4 week treatment period , following an analgesic washout phase of 2 - 7 days , included weekly clinic evaluations , at which the dose was escalated as appropriate , and daily patient diary completion . Pain ( daily ) , stiffness , and physical function ( weekly ) were assessed using the multidimensional , self-administered WOMAC ( visual analog scale version ) question naire . RESULTS Sixty-six eligible patients completed the study . The mean initial and final daily doses of controlled release codeine were 50 mg every 12 h at baseline and 159 mg every 12 h at the final assessment . All variables in the efficacy analysis indicated superiority of controlled release codeine over placebo . The WOMAC pain scale showed an improvement of 44.8 % over baseline in the controlled release codeine group compared with 12.3 % taking placebo ( p = 0.0004 ) . For the WOMAC stiffness and physical function scales the improvements over baseline on controlled release codeine were 47.7 % and 49.3 % , respectively compared with 17.0 % and 17.0 % , respectively , with placebo ( p = 0.003 ; p = 0.0007 ) . Controlled release codeine was also significantly better than placebo on measures of sleep quality and requirement for supplemental acetaminophen . CONCLUSION Single entity controlled release codeine is an effective treatment for pain due to OA of the hip or knee Background The optimal management for severe sprains ( Grade s II and III ) of the lateral ligament complex of the ankle is unclear . The aims of this r and omised controlled trial are to estimate ( 1 ) the clinical effectiveness of three methods of providing mechanical support to the ankle ( below knee cast , Aircast ® brace and Bledsoe ® boot ) in comparison to Tubigrip ® , and ( 2 ) to compare the cost of each strategy , including subsequent health care costs . Methods / design Six hundred and fifty people with a diagnosis of severe sprain are being identified through emergency departments . The study has been design ed to complement routine practice in the emergency setting . Outcomes are recovery of mobility ( primary outcome ) and usual activity , residual symptoms and need for further medical , rehabilitation or surgical treatment . Parallel economic and qualitative studies are being conducted to aid interpretation of the results and to evaluate the cost-effectiveness of the interventions . Discussion This paper highlights the design , methods and operational aspects of a clinical trial of acute injury management in the emergency department A 52-week , multicenter , open-label extension study was performed to evaluate the safety , tolerability , and effectiveness of oxymorphone extended release ( ER ) , a novel tablet formulation of oxymorphone hydrochloride , in 153 patients with moderate to severe chronic osteoarthritis-related pain . Sixty-one patients ( 39.9 % ) completed the study . Common opioid-related nonserious adverse events ( AEs ) caused most withdrawals . However , approximately one-half of withdrawals due to AEs were among opioid-naive patients who received placebo in a previous trial and were started on a dose of 20 mg every 12 hours , suggesting that tolerability can be improved by titrating from a lower initial dose . Mean pain scores initially decreased as previously opioid-naive patients achieved adequate pain relief , reached stable levels after the first 6 weeks , and remained stable at mild levels throughout the remainder of the study ( average pain , 20 - 25 mm on 100-mm Visual Analog Scale ) . Average daily dosing remained stable throughout the study ( median , 40 mg/d ) . At each assessment , at least 80 % of patients rated their global satisfaction with oxymorphone ER as “ excellent , ” “ very good , ” or “ good . ” Oxymorphone ER provides a new 12-hour analgesic for the treatment of moderate to severe chronic osteoarthritis-related pain in patients who may require long-term opioid therapy BACKGROUND This multicenter , parallel-group , 35-day study in adults with osteoarthritis ( OA ) pain evaluated the analgesic efficacy and safety of buprenorphine transdermal system ( BTDS ) design ed for 7-day wear . METHODS Patients with OA pain inadequately controlled with nonsteroidal antiinflammatory drugs or patients who had taken opioids for OA pain within the past year entered a 7-day run-in period during which they took ibuprofen only . Patients with pain > or = on a 0 - 10 scale had their ibuprofen discontinued and were r and omized into a 28-day double-blinded period to receive either BTDS at 1 of 3 dose levels ( 5 , 10 , or 20 microg/b ) or placebo . Doses were titrated to effectiveness over a period of 21 days and maintained for 7 days . No rescue medication was allowed during the study . The primary efficacy measure was the proportion of patients who achieved treatment success , defined as a patient satisfaction score of good , very good , or excellent ( on day 28 or at early discontinuation ) for those who did not discontinue due to ineffective treatment . RESULTS More BTDS-treated patients experienced treatment success than placebo TDS-treated patients ( 44 percent and 32 percent ; odds ratio = 1.66 , p = 0.036 ) . Fewer patients taking BTDS titrated to the highest dose compared with placebo ( p < 0.05 ) . There were two serious adverse events ( both in the placebo group ) and no deaths . The most common ( > or = 5 percent ) adverse events reported in BTDS-treated patients were nausea , headache , dizziness , somnolence , application site pruritus , and vomiting . CONCLUSION Compared with placebo , BTDS treatment was effective in treating patients with moderate to severe pain due to OA of the knee or hip . BTDS was well-tolerated STUDY OBJECTIVE To investigate the effect of once-a-day extended release of morphine sulfate AVINZA ( A-MQD ) on polysomnographic measures of sleep in a population of chronic osteoarthritic pain patients with sleep difficulties . DESIGN Single-center , single-blind , placebo-lead-in , 30 mg or 60 mg . Patients ' sleep and neurocognition were objective ly measured at a sleep laboratory , and patients self-rated their pain , sleep , and other functions . PARTICIPANTS Thirty-four participants ( 26 to 75 years old ) complaining of sleep difficulties and chronic , stable pain secondary to hip or knee osteoarthritis . INTERVENTIONS Participants had a screening visit on current pain medication and then , following a single-blind placebo run-in period , received 30 mg/d of A-MQD for six days . At day 6 , doses for participants with incomplete pain relief on the Brief-Pain-Inventory ( BPI ) pain scale were increased to 60 mg/d . Treatment continued for another eight days at the new dose level ( 14 days for a subgroup at 60 mg/d ) . Sleep was objective ly measured by all-night polysomnography ( PSG ) at screening while on the participants ' current pain therapy , at baseline following a placebo run-in and at the end of treatment while on A-MQD . OUTCOME MEASURES PSG parameters evaluated included Total-Sleep-Time ( TST ) , Wake-timeafter-Sleep-Onset ( WASO ) , Sleep-Efficiency ( SE ) , Latency-to-Persistent Sleep ( LPS ) , Latency-to-REM-sleep , the Number-of-Awakenings ( NAW ) , the time spent in each stage of sleep , and REM-sleep-latency . Subjective evaluations included participants ' estimations of sleep time and sleep quality , the Epworth-Sleepiness-Scale ( ESS ) , the BPI , and participant acceptance of and relief due to current therapy . Assessment s of neurocognitive function were also made . RESULTS Sleep initiation and maintenance tended to improve with A-MQD as demonstrated by the increases in TST and SE and decreases in WASO and NAW as compared with placebo-baseline values . Sleep architecture was preserved by the study drug and some increases in stage 2 and 3/4 sleep were seen compared with placebo baseline . Subjective ratings of sleep quality and sleep time were significantly improved with treatment , as were BPI scores and ratings of medication acceptance and pain relief . A-MQD was generally well tolerated . CONCLUSIONS A-MQD was an effective treatment for pain , and this study treatment was associated with improvement of both objective and subjective sleep parameters in participants with chronic osteoarthritic pain Background This study was design ed to evaluate the utility of transdermal fentanyl ( TDF , Durogesic ® ) for the treatment of pain due to osteoarthritis ( OA ) of the knee or hip , which was not adequately controlled by non-opioid analgesics or weak opioids . The second part of the trial , investigating TDF in patients with rheumatoid arthritis ( RA ) is reported separately . Methods Current analgesia was optimised during a 1-week run-in . Patients then received 28 days treatment with TDF starting at 25 μg/hr , with the option to increase the dose until adequate pain control was achieved . Metoclopramide was taken during the first week and then as needed . Results Of the 159 patients recruited , 75 with OA knee and 44 with OA hip completed the treatment phase , 30 knee and 18 hip patients entered the one-week taper-off phase . The most frequently used maximum dose of TDF was 25 μg/hr . The number of patients with adequate pain control increased during the run-in period from 4 % to 27 % , and further increased during TDF treatment to 88 % on day 28 . From baseline to endpoint , there were significant reductions in pain ( p < 0.001 ) and improvements in functioning ( p < 0.001 ) and physical ( p < 0.001 ) and mental ( p < 0.05 ) health . Scores for ' pain right now ' decreased significantly within 24 hours of starting TDF treatment . TDF was assessed favourably and 84 % of patients would recommend it for OA-related pain . Nausea and vomiting were the most common adverse events ( reported by 32 % and 26 % of patients respectively ) , despite prophylaxis with metoclopramide , which showed limited efficacy in this setting . Conclusion TDF significantly increased pain control , and improved functioning and quality of life . Metoclopramide appeared to be of limited value in preventing nausea and vomiting ; more effective anti-emetic treatment may enable more people to benefit from strong opioids such as TDF . This study suggests that four weeks is a reasonable period to test the benefit of adding TDF to improve pain control in OA patients and that discontinuing therapy in cases of limited benefit creates no major obstacles Concern about abuse/dependence in chronic pain patients taking opioid analgesics may lead to undertreatment of pain , yet little is known about the prevalence of abuse/dependence in these patients and how it differs among analgesic agents . The objective of this study was to assess the prevalence of tramadol abuse compared to nonsteroidal anti-inflammatory drugs ( NSAIDs ) and hydrocodone-containing analgesics in patients with chronic noncancer pain ( CNP ) . The study had three arms . The first arm consisted of subjects prescribed tramadol alone ; the second of subjects r and omized to either NSAIDs or tramadol ; and the third of subjects r and omized to hydrocodone or tramadol . Each investigator received two boxes of prescriptions r and omized so that one in every four prescriptions was for tramadol . Upon deciding on the therapeutically appropriate arm , the physician selected the appropriate box , opened the next envelope and completed the enclosed prescription . After the initial r and omization , physicians could prescribe whatever medication was therapeutically appropriate . A total of 11,352 subjects were enrolled . Up to nine interviews using a structured question naire were conducted over a 12-month period . An algorithm called the " Abuse Index " was developed to identify subjects who were abusing the drug . The primary components of the index were increasing dose without physician approval , use for purpose s other than intended , inability to stop its use , and withdrawal . The percent of subjects who scored positive for abuse at least once during the 12-month follow-up were 2.5 % for NSAIDs , 2.7 % for tramadol , and 4.9 % for hydrocodone . When more than one hit on the algorithm was used as a measure of persistence , abuse rates were 0.5 % for NSAIDs , 0.7 % for tramadol , and 1.2 % for hydrocodone . Thus , the results of this study suggest that the prevalence of abuse/dependence over a 12-month period in a CNP population that was primarily female was equivalent for tramadol and NSAIDs , with both significantly less than the rate for hydrocodone BACKGROUND Although opioid analgesics have well-defined efficacy and safety in treatment of chronic cancer pain , further research is needed to define their role in treatment of chronic noncancer pain . OBJECTIVE To evaluate the effects of controlled-release oxycodone ( OxyContin tablets ) treatment on pain and function and its safety vs placebo and in long-term use in patients with moderate to severe osteoarthritis pain . METHODS One hundred thirty-three patients experiencing persistent osteoarthritis-related pain for at least 1 month were r and omized to double-blind treatment with placebo ( n = 45 ) or 10 mg ( n = 44 ) or 20 mg ( n = 44 ) of controlled-release oxycodone every 12 hours for 14 days . One hundred six patients enrolled in an open-label , 6-month extension trial ; treatment for an additional 12 months was optional . RESULTS Use of controlled-release oxycodone , 20 mg , was superior ( P<.05 ) to placebo in reducing pain intensity and the interference of pain with mood , sleep , and enjoyment of life . During long-term treatment , the mean dose remained stable at approximately 40 mg/d after titration , and pain intensity was stable . Fifty-eight patients completed 6 months of treatment , 41 completed 12 months , and 15 completed 18 months . Common opioid side effects were reported , several of which decreased in duration as therapy continued . CONCLUSIONS Around-the-clock controlled-release oxycodone therapy seemed to be effective and safe for patients with chronic , moderate to severe , osteo-arthritis-related pain . Effective analgesia was accompanied by a reduction in the interference of pain with mood , sleep , and enjoyment of life . Analgesia was maintained during long-term treatment , and the daily dose remained stable after titration . Typical opioid side effects were reported during short- and long-term therapy OBJECTIVE To evaluate the tolerability and efficacy of tapentadol immediate release ( IR ) and oxycodone IR for relief of moderate to severe pain in elderly and nonelderly patients . METHODS Post hoc data analyses were conducted on a 90-day r and omized , phase 3 , double-blind , flexible-dose study ( Clinical Trials.gov : NCT00364546 ) of adults with moderate to severe lower back pain or osteoarthritis pain who received tapentadol IR 50 mg or 100 mg , or oxycodone HCl IR 10 mg or 15 mg every 4 h to 6 h as needed for pain relief . Treatment-emergent adverse events and study discontinuations were recorded . RESULTS Data from 849 patients r and omly assigned ( 4:1 ratio ) to treatment with a study drug ( tapentadol IR [ n=679 ] or oxycodone IR [ n=170 ] ) were analyzed according to age ( younger than 65 years of age [ nonelderly ] , or 65 years of age or older [ elderly ] ) and treatment group . Among elderly patients , incidences of constipation ( 19.0 % versus 35.6 % ) and nausea or vomiting ( 30.4 % versus 51.1 % ) were significantly lower with tapentadol IR versus oxycodone IR ( all P<0.05 ) . Initial onsets of nausea and constipation occurred significantly later with tapentadol IR versus oxycodone IR ( both P<=0.031 ) . Tapentadol IR-treated elderly patients had a lower percentage of days with constipation than oxycodone IR-treated patients ( P=0.020 ) . For tapentadol IR- and oxycodone IR-treated elderly patients , respectively , incidences of study discontinuation due to gastrointestinal treatment-emergent adverse events were 15.8 % and 24.4 % ( P=0.190 ) . Tapentadol IR and oxycodone IR provided similar pain relief , with no overall age-dependent efficacy differences ( mean pain scores [ 11-point numerical rating scale ] decreased from 7.0 and 7.2 at baseline , to 4.9 and 5.2 at end point , respectively ) . CONCLUSIONS Tapentadol IR was safe and effective for the relief of lower back pain and osteoarthritis pain in elderly patients , and was associated with a better gastrointestinal tolerability profile than oxycodone IR Other members of the guideline development and project groups are listed in the Appendix This guideline addresses the appropriate use of non-steroidal anti-inflammatory drugs in the primary care treatment of patients with joint pain believed to be caused by degenerative arthritis . It does not consider therapies other than drug treatment . General practitioners must use their professional knowledge and judgement when applying guideline recommendations to the management of individual patients . They should note the information , contraindications , interactions , and side effects contained in the British National Formulary.1 This is a summary of the full version of the guideline .2 In this article , the statements accompanied by categories of evidence ( cited as Ia , Ib , IIa , IIb , III , and IV ) and recommendations classified according to their strength ( A , B , C , or D ) are as described previously and are summarised in the box.3 # # # Summary points The methods used to develop the guideline have been described previously.3Briefly , we search ed the electronic data bases Medline and Embase , using a combination of subject heading and free text terms aim ed at locating systematic review s , meta-analyses , r and omised trials , quality of life studies , and economic studies . The search was backed up by the expert knowledge and experience of group members . # # # Strength of Current treatment guidelines advocate opioids for arthritis when st and ard analgesics produce inadequate relief . Efficacy , adverse effects ( AEs ) , dosing regimens , physician expertise and patient preference influence treatment selection . This study assessed transdermal fentanyl ( TDF ) as a treatment option for osteoarthritis ( OA ) patients . This prospect i ve , Canadian open-label , 8-week trial assessed the efficacy and safety of TDF in patients with OA of hip or knee with moderate-to-severe target joint pain inadequately controlled using weak opioids . TDF was initiated at 25 mcg/h and titrated to optimal pain control . Rescue acetaminophen 500 mg was allowed ( maximum 4 g/day ) . The main endpoint was improvement in pain control assessment rating ( five rating categories ) ; pain intensity ( 0–10 numerical scale ) , functionality ( WOMAC-OA Index ) , health-related quality of life ( SF-36 Health Survey ) and global impression were also evaluated . Eighty-one patients ( 61 % female , mean age 60 years ) were enrolled ; 62 were evaluable . All had failed on previous weak opioid therapy , primarily codeine or codeine combinations . At treatment end , 65 % rated pain control as improved ( Pain Control Assessment rating change ≥1 category ; p < 0.0001 ) ; mean change in pain intensity was a reduction of greater than 2 ( p < 0.0001 ) ; almost 50 % were maintained on TDF 25 mcg/h with less than 1.3 g/day of rescue acetaminophen . At 1 month and end of treatment , changes in the SF-36 physical global scale and individual sub-scores for the pain index and role-physical scales were highly significant ( p < 0.0001 ) . Improvement in functionality was noted at 1 month and at end of treatment with significant reductions in total WOMAC score , individual pain , stiffness and physical function sub-scores ( p < 0.0001 ) . AEs causing discontinuation ( n = 32 ) included nausea , dizziness and vomiting . Most treatment-related AEs were mild to moderate in intensity . TDF improved pain control , functionality and health-related quality of life in these patients . The findings support current recommendations for use of opioids such as TDF as a treatment option for a sub- population of patients with OA pain OBJECTIVE Although common treatments for osteoarthritis ( OA ) pain , such as nonsteroidal antiinflammatory drugs ( NSAIDs ) , simple analgesics , and weak opioids , provide relief in some cases , they fail to control pain or are poorly tolerated in many cases . Strong opioids have been used to successfully treat several types of noncancer pain but have rarely been tested in controlled studies . Therefore , we tested the effects of transdermal fentanyl ( TDF ) in patients with moderate-to-severe OA pain , in a placebo-controlled study . METHODS The cohort comprised patients with radiologically confirmed OA of the hip or knee ( meeting the American College of Rheumatology criteria ) requiring joint replacement and with moderate-to-severe pain that had been inadequately controlled by weak opioids . The patients were r and omized to receive TDF or placebo for 6 weeks after a 1-week pretreatment run-in phase . During study treatment , previously prescribed NSAIDs and simple analgesics were continued , but weak opioids were discontinued . All patients had access to paracetamol and metoclopramide . Pain was recorded on a visual analog scale ( VAS ) , and function was assessed using the Western Ontario and McMaster Universities Osteoarthritis Index ( WOMAC ) . RESULTS Data were available for 399 patients ( 202 receiving TDF , 197 receiving placebo ) , of whom 199 ( 50 % ) completed the study . TDF provided significantly better pain relief than placebo , as demonstrated by the primary outcome measure ( area under the curve for VAS scores -20 in the TDF group versus -14.6 in the placebo group ; P = 0.007 ) . TDF was also associated with significantly better overall WOMAC scores and pain scores . The most common adverse events were nausea , vomiting , and somnolence , and these occurred more often in the TDF group . CONCLUSION TDF can reduce pain and improve function in patients with knee or hip OA Objective : This study , lasting up to 90 days , was undertaken in patients with osteoarthritis with persistent moderate to severe pain uncontrolled by st and ard therapy ( nonsteroidal anti-inflammatory drugs , acetaminophen , and /or short-acting opioids ) to evaluate functional outcomes , as well as efficacy and safety , of controlled-release oxycodone versus placebo . Methods : One hundred seven patients received either controlled-release oxycodone or placebo every 12 hours in this double blind , r and omized , placebo-controlled , parallel-group study . Stable previous regimens of acetaminophen or nonsteroidal anti-inflammatory agents were allowed to continue . Primary efficacy variables included Brief Pain Inventory average pain intensity scores at completion of initial titration , Western Ontario and McMaster Universities Osteoarthritis Index scores at days 30 and 60 , and the percentage of patients discontinuing due to inadequate pain control . Results : Controlled-release oxycodone was significantly superior to placebo in decreasing average pain intensity and in reducing pain-induced interference with general activity , walking ability ( except at day 30 ) , and normal work , as well as mood , sleep , relations with people ( at days 60 and 90 ) , and enjoyment in life . Daily functioning , as measured by the Western Ontario and McMaster Universities Osteoarthritis Index , was also significantly improved in the controlled-release oxycodone group . In the placebo group , a significantly greater percentage of patients discontinued due to inadequate pain control . Adverse events were consistent with opioid adverse events , and no safety concerns were noted . Discussion : Treatment with controlled-release oxycodone of patients with osteoarthritis with persistent moderate to severe pain uncontrolled by st and ard therapy result ed in significant pain control and improvements in physical functioning A double-blind , placebo-controlled , between-patient evaluation of the analgesic properties of oral meptazinol was carried out in 60 patients suffering from chronic pain due to rheumatoid arthritis and osteoarthritis . Patients were allocated , at r and om , to receive either 200 mg meptazinol every 3 to 6 hours as required or identical matching placebo for a total period of 72 hours . Data from 57 patients ( 30 on meptazinol , 27 on placebo ) were suitable for analysis . Pain intensity in five major categories was assessed using a 4-point verbal rating scale by a clinician before the first dose and at the end of the trial period . Patients performed a self- assessment of pain prior to taking the first dose and subsequently at 2,4,24 , 48 and 72 hours using 100 mm visual analogue scales and verbal rating scales . The clinician-rated pain scores showed no significant difference between the two groups in initial pain intensity . After 72-hours ' treatment , there was a significant ( p less than l.01 ) reduction in pain intensity after 2 hours which was maintained throughout the trial period . There was no significant reduction in pain intensity in patients taking placebo . Visual analogue scale scores and pain intensity difference scores showed significantly ( p less than 0.01 ) greater reduction in pain intensity at all time points in the meptazinol- treated patients . ( ABSTRACT TRUNCATED AT 250 WORDS The study aim was to address the need for objective markers of pain-modifying interventions by testing the hypothesis that selective gait measures of knee joint loading can distinguish differences between non-steroidal anti-inflammatory ( NSAID ) , analgesic treatment ( opioid-receptor agonist ) , and placebo in patients medial knee osteoarthritis ( OA ) . A r and omized , single-blind washout , double-blind treatment , double-dummy cross-over trial using three treatment arms placebo , opioid ( Oxycodone ) , and NSAID ( Celecoxib ) in medial compartment knee OA patients . Six patients with Kellgren-Lawrence radiographic severity grade s of 2 or 3 completed six testing sessions ( gait and pain assessment ) at 2-week intervals . A significant increase was found in the knee total reaction moment and vertical ground reaction force ( GRF ) for Celecoxib compared to placebo ( p=0.005 , p=0.003 ) , but not for Oxycodone compared to placebo ( p=0.20 , p=0.27 ) treatments . Walking speed was significantly higher for the Celecoxib and Oxycodone compared to placebo treatment ( p=0.041 and p=0.031 , respectively ) . Self-reported function ( WOMAC scores ) was not different among treatments ( p>0.05 ) . The changes in total reaction moments and GRFs for only the NSAID suggest that greater increases in joint loading occurs when joint inflammation is treated in addition to pain . The total knee reaction moment , representing the magnitude of the extrinsic moment , appears to be a sensitive marker , more so than self-reported metrics , for evaluating knee OA treatment effects BACKGROUND AND OBJECTIVES Osteoarthritis is the most common joint disease among elderly people . This study aim ed at comparing the analgesic effects of intra-articular bupivacaine and morphine in knee osteoarthritis patients . METHODS Thirty-nine patients were included in this r and omized double-blind study and divided in two groups : G1 ( n = 18 ) patients were given intra-articular 1 mg ( 1 mL ) morphine diluted in 9 mL of 0.9 % saline , while G2 ( n = 21 ) received intra-articular 25 mg ( 10 mL ) of 0.25 % plain bupivacaine . Pain intensity was evaluated by numerical and verbal scale at 0 , 30 , 60 minutes and 7 days at rest and in movement . Evaluated parameters were analgesic supplementation requirement with paracetamol ( 500 mg ) , total analgesic dose throughout the study , analgesia duration and quality ( according to patient ) . RESULTS From 39 patients , 31 have completed the study . There has been no significant difference in pain intensity at rest and in movement between groups in all studied moments . There has been no difference between groups in time between solution administration and need for analgesic supplementation . Mean paracetamol dose in the first day was 796 mg for G1 and 950 mg for G2 ; supplementation during the week was 3578 mg for G1 and 5333 mg for G2 . CONCLUSIONS The analgesic effect of intra-articular 1 mg morphine and 25 mg of 0.25 % plain bupivacaine was similar OBJECTIVE To evaluate the efficacy and safety of an encapsulated , highly viscous formulation of extended-release oxycodone design ed to resist common physical manipulation and chemical challenges ( Remoxy ; King Pharmaceuticals , Inc. , Bristol , TV , which was acquired by Pfizer Inc. in March 2011 ) . DESIGN An enriched enrollment r and omized withdrawal trial design was used whereby patients entered a double-blind , multicenter , placebo-controlled trial after completing an open-label titration phase . SETTING Sixty-one US clinics . PATIENTS All patients ( 40 - 75 years ) had experienced moderate to severe chronic osteoarthritic pain in the hip or knee for > or = 3 months . INTERVENTIONS During 2 weeks of open-label treatment ( N = 558 ) , patients were titrated from Remoxy 5 mg twice daily ( bid ) to 20 mg bid . Patients who tolerated the drug were r and omly assigned to Remoxy or placebo bid for 12 weeks . Dose titration was permitted during weeks 1 - 4 ( range , 10 - 80 mg/d ) and fixed thereafter . MAIN OUTCOME MEASURES The area under the curve ( AUC ) for change in pain intensity ( PI ) scores from prer and omization to the end of the 12-week period was the primary endpoint . Patient assessment of quality of analgesia , global assessment of study medication , quality of life , and safety were also evaluated . RESULTS The mean AUC for change in PI score was significantly greater for Remoxy than for placebo ( p = 0.007 ) . Patients receiving Remoxy reported significantly better scores on quality of analgesia ( p = 0.004 ) and global assessment of study medication ( p = 0.007 ) when compared with patients receiving placebo . Remoxy had a safety profile consistent with other opioids . CONCLUSIONS Remoxy significantly improved analgesia among patients with moderate to severe chronic osteoarthritic pain with an adverse event profile similar to other opioids BACKGROUND The OARSI St and ing Committee for Clinical Trials Response Criteria Initiative had developed two sets of responder criteria to present the results of changes after treatment in three symptomatic domains ( pain , function , and patient 's global assessment ) as a single variable for clinical trials ( 1 ) . For each domain , a response was defined by both a relative and an absolute change , with different cut-offs with regard to the drug , the route of administration and the OA localization . OBJECTIVE To propose a simplified set of responder criteria with a similar cut-off , whatever the drug , the route or the OA localization . METHODS Data driven approach : ( 1 ) Two data bases were considered : the " elaboration " data base with which the formal OARSI sets of responder criteria were elaborated , and the " revisit " data base . ( 2 ) Six different scenarios were evaluated : The two formal OARSI sets of criteria ; Four proposed scenarios of simplified sets of criteria . Data from clinical r and omized blinded placebo controlled trials were used to evaluate the performances of the two formal scenarios with two different data bases ( " elaboration " versus " revisit " ) and those of the four proposed simplified scenarios within the " revisit " data base . The placebo effect , active effect , treatment effect , and the required sample arm size to obtain the placebo effect and the active treatment effect observed were the performances evaluated for each of the six scenarios . Experts ' opinion approach : Results were discussed among the participants of the OMERACT VI meeting , who voted to select the definite OMERACT-OARSI set of criteria ( one of the six evaluated scenarios ) . RESULTS Data driven approach : Fourteen trials totaling 1886 OA patients and fifteen studies involving 8164 OA patients were evaluated in the " elaboration " and the " revisit " data bases respectively . The variability of the performances observed in the " revisit " data base when using the different simplified scenarios was similar to that observed between the two data bases ( " elaboration " versus " revisit " ) when using the formal scenarios . The treatment effect and the required sample arm size were similar for each set of criteria . Experts ' opinion approach : According to the experts , these two previous performances were the most important of an optimal set of responder criteria . They chose the set of criteria considering both pain and function as evaluation domain and requiring an absolute change and a relative change from baseline to define a response , with similar cut-offs whatever the drug , the route of administration or the OA localization . CONCLUSION This data driven and experts ' opinion approach is the basis for proposing an optimal simplified set of responder criteria for OA clinical trials . Other studies , using other sets of OA patients , are required in order to further vali date this proposed OMERACT-OARSI set of criteria & NA ; The aim of the study was epidemiologically to evaluate the long‐term effects of opioids on pain relief , quality of life and functional capacity in long‐term/chronic non‐cancer pain . The study was based on data from the 2000 Danish Health and Morbidity Survey . As part of a representative National r and om sample of 16,684 individuals ( > 16 years of age ) , 10,066 took part in an interview and completed a self‐administered question naire . Cancer patients were excluded . The interview and the self‐administered question naire included questions on chronic/long‐lasting pain ( > 6 months ) , health‐related quality of life ( SF‐36 ) , use of the health care system , functional capabilities , satisfaction with medical pain treatment and regular or continuous use of medications . Participants reporting pain were divided into opioid and non‐opioid users . The analyses were adjusted for age , gender , concomitant use of anxiolytics and antidepressants and pain intensity . Pain relief , quality of life and functional capacity among opioid users were compared with non‐opioid users . Opioid usage was significantly associated with reporting of moderate/severe or very severe pain , poor self‐rated health , not being engaged in employment , higher use of the health care system , and a negative influence on quality of life as registered in all items in SF‐36 . Because of the cross‐sectional nature causative relationships can not be ascertained . However , it is remarkable that opioid treatment of long‐term/chronic non‐cancer pain does not seem to fulfil any of the key outcome opioid treatment goals : pain relief , improved quality of life and improved functional capacity & NA ; This r and omized , double‐blind , multi‐centre study was undertaken to evaluate the efficacy and safety of treatment for 4 weeks with codeine plus paracetamol versus paracetamol in relieving chronic pain due to osteoarthritis of the hip . A total of 158 outclinic patients entered the study . Eighty‐three patients ( mean age 66 years ) were treated with codeine 60 mg plus paracetamol 1 g 3 times daily , and 75 patients ( mean age 67 years ) with paracetamol 1 g 3 times daily . Ibuprofen 400 mg was prescribed as rescue medication . Due to an unexpected high rate of adverse drug reactions , the study was closed before the planned 400 patients had entered . Over weeks 1–4 , 87 % , 64 % , 61 % and 52 % of patients in the codeine plus paracetamol group , and 38 % , 31 % , 22 % and 29 % of patients in the paracetamol group had one or more adverse drug reactions . Significantly more patients in the codeine plus paracetamol group had adverse drug reactions in each of the 4 weeks . Nausea , dizziness , vomiting and constipation were predominant adverse reactions in the codeine plus paracetamol group . During the first week of treatment , 30 patients ( 36 % ) in the codeine plus paracetamol group and 9 ( 12 % ) in the paracetamol group dropped out . As evaluated from patients completing the first week of treatment , the pain intensity during that week compared to their baseline pain was significantly lower in the codeine plus paracetamol group than in the paracetamol group . Moreover , during the first week the paracetamol group received rescue medicine significantly more frequently . In conclusion , when evaluated after 7 days of treatment , the daily addition of codeine 180 mg to paracetamol 3 g significantly reduced the intensity of chronic pain due to osteoarthritis of the hip joint . However , several adverse drug reactions , mainly of the gastrointestinal tract , and the larger number of patients withdrawing from treatment means that the addition of such doses of codeine can not be recommended for longer‐term treatment of chronic pain in elderly patients A report is given about a multicentric double-blind test for proof of effectiveness of two new suppository preparations with and without codeine against comparable remedies . Dolo Visano Supp . sine codeino showed a slight superiority over the reference preparation . This was proved above all for the influence upon pain and muscular overstrain . The better tolerability was marked . Dolo Visano Supp . ( with codeine ) showed advantages against the reference preparation . It was used in cases of severe pain , and in 88 % it had a very good effect , whereas for the reference preparation this applied only in 67,9 % . The assessment s of physician and patients were almost alike . The myotonolytic effect has been proved equally for both of the new suppository preparations OBJECTIVE To compare oxymorphone extended release ( ER ) and placebo on indices of pain , function , and safety in patients with chronic osteoarthritis ( OA ) pain . DESIGN In this multicenter , double-blind , placebo- and active-controlled , parallel-group , dose-ranging study , patients were r and omized to oxymorphone ER 20 mg ( N = 121 ) , oxymorphone ER 40 mg ( N = 121 ) , oxycodone controlled release 20 mg ( N = 125 ) , or placebo ( N = 124 ) every 12 hours . The primary efficacy end point was change in arthritis pain intensity ( visual analog scale , 0 - 100 ) from baseline to week 3 for the oxymorphone ER 40 mg group versus placebo . RESULTS The primary end point was achieved : the week 3 oxymorphone ER least squares mean difference ( LSMD ) from placebo was -9.0 ( 95 % confidence interval [ CI ] : -16.2 to -1.8 ; P = 0.015 ) . Secondary efficacy analysis showed similar improvements at week 4 ( LSMD from placebo , -10.3 [ 95 % CI : -17.7 to -2.8 ] ; P = 0.007 ) and with oxymorphone ER 20 mg at week 3 ( LSMD from placebo , -7.7 [ 95 % CI : -15.0 to -0.4 ] ; P = 0.039 ) and week 4 ( LSMD from placebo , -7.5 [ 95 % CI : -15.0 to 0.0 ] ; P = 0.050 ) . Weeks 3 and 4 pain intensity decreased by approximately 30 - 40 % . Oxymorphone ER 20 and 40 mg improved from baseline on the Western Ontario and McMaster Universities Osteoarthritis Composite Index and pain and physical function subscales at week 4 . Adverse events in all opioid groups included mild to moderate nausea , constipation , and somnolence . CONCLUSIONS In this short-term study , oxymorphone ER was superior to placebo for relieving pain and improving function in patients with moderate to severe chronic OA pain , and is an alternative to other sustained-release opioids Twenty-eight patients with osteoarthritis participated in a prospect i ve , double-blind , cross-over study to compare the safety and efficacy of a new combination analgesic containing ibuprofen 200 mg , paracetamol 250 mg and codeine phosphate 10 mg per tablet ( Myprodol ; Rio Ethicals ) with a st and ard treatment regimen ( ibuprofen 200 mg per tablet ) . The combination tablet was found to provide significantly better pain relief than ibuprofen alone ( P less than 0.05 ) . Analysis of the results of haematological , hepatic and renal function tests showed no statistically significant differences between treatments . No serious side-effects or clinical ly important changes were encountered with either drug BACKGROUND Tapentadol is a novel , central ly acting analgesic with 2 mechanisms of action : µ-opioid receptor agonism and norepinephrine reuptake inhibition . This r and omized , open-label phase 3 study ( Clinical Trials.gov Identifier : NCT00361504 ) assessed the long-term safety and tolerability of tapentadol extended release ( ER ) in patients with chronic knee or hip osteoarthritis pain or low back pain . METHODS Patients were r and omized 4:1 to receive controlled , adjustable , oral , twice-daily doses of tapentadol ER ( 100 to 250 mg ) or oxycodone HCl controlled release ( CR ; 20 to 50 mg ) for up to 1 year . Efficacy evaluations included assessment s at each study visit of average pain intensity ( 11-point numerical rating scale ) over the preceding 24 hours . Treatment-emergent adverse events ( TEAEs ) and discontinuations were monitored throughout the study . RESULTS A total of 1,117 patients received at least 1 dose of study drug . Mean ( st and ard error ) pain intensity scores in the tapentadol ER and oxycodone CR groups , respectively , were 7.6 ( 0.05 ) and 7.6 ( 0.11 ) at baseline and decreased to 4.4 ( 0.09 ) and 4.5 ( 0.17 ) at endpoint . The overall incidence of TEAEs was 85.7 % in the tapentadol ER group and 90.6 % in the oxycodone CR group . In the tapentadol ER and oxycodone CR groups , respectively , TEAEs led to discontinuation in 22.1 % and 36.8 % of patients ; gastrointestinal TEAEs led to discontinuation in 8.6 % and 21.5 % of patients . CONCLUSION Tapentadol ER ( 100 to 250 mg bid ) was associated with better gastrointestinal tolerability than oxycodone HCl CR ( 20 to 50 mg bid ) and provided sustainable relief of moderate to severe chronic knee or hip osteoarthritis or low back pain for up to 1 year & NA ; Morphine is increasingly used in patients with chronic non‐cancer pain , but a major concern associated with chronic use relates to possible cognitive side‐effects . The aim of this long‐term prospect i ve study was to evaluate the cognitive impact of oral sustained release morphine in patients with non‐cancer pain . A battery of neuropsychological tests to explore attention , psychomotor speed and memory was administered . The effects of morphine on pain , quality of life , mood , subjective memory impairment and side‐effects were also investigated . Evaluations were performed at baseline in patients free from opioids and then after 3 , 6 and 12 months . Twenty‐eight patients were included : 18 received oral sustained morphine ( range 40–140 mg/day ) , ten patients stopped morphine prematurely because of side‐effects or insufficient pain relief and were followed as a control group . There was no impairment of any neuropsychological variable over time in the morphine treated patients in comparison with the control group . Two measures of information processing speed – the Stroop interference score and the digit symbol test were improved at 6 and 12 months and there were significant correlations with the pain relief and improvement of mood . Self‐reported memory impairment improved notably in responders to morphine . Morphine induced persisting effects on pain , and to a lesser extent on quality of life and mood . The visual analog scale score for side‐effects increased at 12 months and essentially consisted of gastrointestinal disorders . This study demonstrates that 12 months treatment with oral morphine does not disrupt cognitive functioning in patients with chronic non‐cancer pain and instead results in moderate improvement of some aspects of cognitive functioning , as a consequence of the pain relief and concomitant improvement of well‐being and mood Abstract Objective : To assess the efficacy and safety of morphine sulfate and naltrexone hydrochloride extended release capsules ( EMBEDA ® ; MS-sNT ) , which contain morphine sulfate pellets with a sequestered naltrexone core , in treating patients with chronic , moderate-to-severe osteoarthritis ( hip or knee ) pain . Patients and Methods : This phase 3 study had an enriched-enrollment , r and omized-withdrawal , double-blind , multicenter design . Patients ( N = 547 ) were titrated to an effective dose of MS-sNT ( 20–160 mg/day ) . Responders ( n = 344 ) were r and omized to 12 weeks maintenance with an effective MS-sNT dose or were tapered to placebo over 2 weeks . The primary efficacy measure was the change from baseline ( CFB ) in diary average-pain scores ( 0–10 scale , Brief Pain Inventory [ BPI ] ) from r and omization to the last 7 days of the maintenance period . Secondary efficacy measures included the remaining BPI scores and Western Ontario and McMaster Universities ( WOMAC ) Osteoarthritis Index . Opioid withdrawal symptoms were assessed by the Clinical Opiate Withdrawal Scale ( COWS ) and Subjective Opiate Withdrawal Scale ( SOWS ) . The study ran from January 10 , 2007 through November 8 , 2007 . Results : MS-sNT maintained pain control better than placebo ( mean CFB , diary average-pain score , −0.2 ± 1.9 vs + 0.3 ± 2.1 ; P = 0.045 ) . Change from baseline for MS-sNT pain-diary score ( worst , least , average , current ) was superior during the maintenance period visits , weeks 2 to 12 ( P < 0.05 ) . WOMAC composite score CFB was superior at most visits . MS-sNT was generally well tolerated , with a typical morphine safety profile . No patient taking MS-sNT as directed experienced withdrawal symptoms . Conclusion : MS-sNT provided effective analgesia in patients with chronic , moderate-to-severe osteoarthritis pain , with a safety profile typical of morphine-containing products . Naltrexone sequestered in MS-sNT had no clinical ly relevant effect when MS-sNT was taken as directed OBJECTIVES The primary objective of this study was to assess the efficacy and tolerability of tapentadol immediate release ( IR ) in patients who were c and i date s for joint replacement surgery due to end-stage joint disease . A secondary objective was to compare tapentadol IR with oxycodone HCl IR with respect to efficacy and prespecified tolerability end points . METHODS This 10-day , Phase III , r and omized , double-blind , active- and placebo-controlled study compared the efficacy and tolerability of tapentadol IR , oxycodone HCl IR , and placebo in patients with uncontrolled osteoarthritis pain who were c and i date s for primary replacement of the hip or knee as a result of end-stage degenerative joint disease . Patients received tapentadol IR 50 mg , tapentadol IR 75 mg , oxycodone HCl IR 10 mg , or placebo every 4 to 6 hours during waking hours . The primary end point was the sum of pain intensity difference ( SPID ) over 5 days . Secondary efficacy end points included 2- and 10-day SPID ; 2- , 5- , and 10-day total pain relief ( TOTPAR ) ; and the sum of total pain relief and pain intensity difference ( SPRID ) . Prespecified noninferiority comparisons with oxycodone HCl IR were performed with respect to efficacy ( based on 5-day SPID ) and tolerability ( based on incidence of the reported adverse events ( AEs ) of nausea and /or vomiting and constipation ) . RESULTS Of 666 patients originally enrolled , 659 were included in the efficacy analysis ( 51 % male ; 91 % white ; mean age , 61.2 years ; mean weight , 97 kg ) . Five-day SPID was significantly lower in those treated with tapentadol IR ( tapentadol IR 50 mg : least squares mean difference [ LSMD ] = 101.2 [ 95 % CI , 54.58- 147.89 ] ; tapentadol IR 75 mg : LSMD = 97.5 [ 95 % CI , 51.81 - 143.26 ] ) or oxycodone HCl IR ( LSMD = 111.9 [ 95 % CI , 66.49 - 157.38 ] ) ( all , P < 0.001 ) . Tapentadol IR 50 and 75 mg and oxycodone HCl IR 10 mg were associated with significant reductions in pain intensity compared with placebo , based on 2- and 10-day SPID and 2- , 5- , and 10-day TOTPAR and SPRID ( all , P < 0.001 ) . The efficacy of tapentadol IR 50 and 75 mg was noninferior to that of oxycodone HCl IR 10 mg ; however , the incidence of selected gastrointestinal AEs ( nausea , vomiting , and constipation ) was significantly lower for both doses of tapentadol IR compared with oxycodone HCl IR 10 mg ( nominal P < 0.001 ) . The odds ratios for nausea and /or vomiting for tapentadol IR 50 and 75 mg relative to oxycodone HCl IR 10 mg were 0.21 ( 95 % CI , 0.128 - 0.339 ) and 0.32 ( 95 % CI , 0.204 - 0.501 ) , respectively ; for constipation , the corresponding odds ratios were 0.13 ( 95 % CI , 0.057 - 0.302 ) and 0.20 ( 95 % CI , 0.098 - 0.398 ) . Rates of treatment discontinuation were 18 % ( 28/157 ) in the tapentadol IR 50-mg group , 26 % ( 43/168 ) in the tapentadol IR 75-mg group , 35 % ( 60/172 ) in the oxycodone HCl IR 10-mg group , and 10 % ( 17/169 ) in the placebo group . In a post hoc analysis , tapentadol IR 50 mg was associated with a significantly lower incidence of treatment discontinuation than was oxycodone HCl IR 10 mg ( P < 0.001 ) . CONCLUSIONS In these patients with uncontrolled osteoarthritis pain who were awaiting joint replacement surgery , tapentadol IR 50 and 75 mg were associated with analgesia that was noninferior to that provided by oxycodone HCl IR 10 mg . Tapentadol treatment was associated with improved gastrointestinal tolerability OBJECTIVE To compare the efficacy and safety of controlled release oxycodone given every 12 h around the clock with immediate release oxycodone-acetaminophen ( APAP ) given 4 times daily for osteoarthritis ( OA ) pain . METHODS Adults ( n=167 ) with moderate to severe OA pain despite regular use of nonsteroidal antiinflammatory drugs ( NSAID ) entered open label titration for 30 days with immediate release oxycodone qid ; 107 qualified for r and omization to double blind , parallel group treatment for 30 days with placebo , controlled release oxycodone , or immediate release oxycodone-APAP . RESULTS Following titration with immediate release oxycodone , mean ( SE ) pain intensity ( 0 , none to 3 , severe ) decreased from 2.44 ( 0.04 ) to 1.38 ( 0.05 ) ( p=0.0001 ) , and quality of sleep ( 1 , very poor ; 5 , excellent ) improved from 2.58 ( 0.08 ) to 3.57 ( 0.07 ) ( p=0.0001 ) . Mean dose was about 40 mg/day . Pain intensity and quality of sleep were significantly improved in both active groups compared with the placebo group ( p < or = 0.05 ) during the double blind trial . Pain intensity and sleep scores were comparable in both active groups during double blind treatment . Nausea ( p=0.03 ) and dry mouth ( p=0.09 ) were less common with controlled release oxycodone than immediate release oxycodone-APAP . CONCLUSION Controlled release oxycodone q12h and immediate release oxycodone-APAP qid , added to NSAID , were superior to placebo for reducing OA pain and improving quality of sleep . The active treatments provided comparable pain control and sleep quality . Controlled release oxycodone was associated with a lower incidence of some side effects UNLABELLED Oxytrex is a novel drug that combines oxycodone with ultralow-dose naltrexone , an opioid antagonist . Ultralow-dose opioid antagonists have been demonstrated to enhance and prolong opiate analgesia and alleviate opioid tolerance and withdrawal in rodents . This 3-week , Phase II clinical trial assessed safety and analgesic efficacy of Oxytrex in patients with moderate to severe pain from osteoarthritis . Patients with a pain score > or = 5 received placebo , oxycodone 4 times a day ( qid ) , Oxytrex qid , or Oxytrex twice a day ( bid ) . All active treatment groups received the same total daily dose and dose escalation of oxycodone starting at 10 and ending at 40 mg/day . Importantly , the Oxytrex bid group received a lower daily dose of naltrexone than Oxytrex qid ( 0.002 vs 0.004 mg/day ) . Oxytrex bid produced a 39 % reduction in pain intensity , which was significantly greater than that of placebo ( P < .001 ) , oxycodone qid ( P = .006 ) , and Oxytrex qid ( P = .003 ) . Oxytrex bid was also superior to placebo in quality of analgesia ( P = .002 ) , duration of pain control each day ( P = .05 ) , patients ' global assessment s ( P = .04 ) , and the Western Ontario and MacMaster Universities Osteoarthritis Index total score ( P = .03 ) . The incidence of side effects was comparable between active treatments . In this Phase II dose-ranging study , Oxytrex bid demonstrated greater pain relief with a more convenient dosing schedule compared to oxycodone qid . PERSPECTIVE Pre clinical data have shown ultralow-dose opioid antagonists to enhance and prolong opioid analgesia while reducing analgesic tolerance and physical dependence . Recent molecular pharmacology data show a mechanism of action to be the prevention of aberrant G protein coupling by opioid receptors that underlies opioid tolerance and dependence & NA ; The analgesic efficacy of 200 mg ibuprofen plus 30 mg codeine , 200 mg ibuprofen and placebo was investigated in a new analgesic evaluation model using single‐ and repeated‐dose administration . The study was a double‐blind r and omized cross‐over investigation in 26 coxarthrosis patients with persistent pain . After a washout period of at least 2 days with paracetamol available as rescue analgesic , each of the 3 treatments was administered in a total of 6 doses during 24 h. The hourly pain intensity was recorded on a 100‐mm visual analogue scale ( VAS ) for 8 h after the 1st and the 6th dose . The pretreatment VAS score was 31–37 mm . After the 1st dose the 8‐h mean pain intensity values were 25 , 27 , and 26 mm after ibuprofen plus codeine , ibuprofen , and placebo , respectively . Following another 5 doses every 4 h the corresponding values were 10 , 17 and 29 mm . Repeated administration of both active drugs reduced the pain intensity significantly . The analgesic efficacy of ibuprofen plus codeine was significantly superior to that of ibuprofen which was , in turn , superior to that of placebo . In conclusion , analgesic efficacy was better differentiated after repeated‐dose than after single‐dose administration . The present study design was able to differentiate between 200 mg ibuprofen plus 30 mg codeine and 200 mg ibuprofen alone in a relatively small number of patients A r and omized , 4-week , double-blind trial followed by an open-label extension trial assessed the efficacy and safety of a once-daily , extended-release morphine formulation ( Avinza ( previously referred to as Morphelan ) ) in 295 patients with chronic , moderate-to-severe osteoarthritis pain who had failed to obtain adequate pain relief with NSAIDs and acetaminophen . Participants received one of four treatments : Avinza 30 mg once daily ( QAM or QPM ) , MS Contin(R ) 15 mg twice daily , or placebo twice daily . Patients ( n = 181 ) received Avinza QAM or QPM during the 26-week open-label extension trial and could increase their dose to optimize pain control . Avinza and MS Contin reduced pain and improved several sleep measures versus placebo . Analgesic efficacy was comparable between Avinza and MS Contin ; however , Avinza QAM demonstrated greater improvements in overall quality of sleep . The most common adverse events were constipation and nausea . The majority of AEs occurred at a similar incidence among the active treatment groups BACKGROUND Oxymorphone extended release ( ER ) is a tablet formulation of the mu-opioid agonist oxymorphone design ed to achieve a low peak-to-trough fluctuation in plasma concentrations over a 12-hour dosing period . OBJECTIVE This study compared the analgesic efficacy , dose response , and tolerability of 3 doses of oxymorphone ER given every 12 hours with those of placebo in patients with pain related to osteoarthritis ( OA ) of the hip or knee . METHODS This was a 2-week , multicenter , r and omized , double-blind , placebo-controlled , dose-ranging , Phase III trial . Patients with OA of the hip or knee who were receiving an opioid medication for chronic , moderate to severe pain or who were judged by the investigator to have received suboptimal analgesia with nonopioid analgesics entered a 2- to 7-day washout of analgesic medication . When pain in the index joint was > 40 mm on a 100-mm visual analog scale ( VAS ) , patients were r and omized to receive 1 of 4 regimens : oxymorphone ER 10 mg q12h during weeks 1 and 2 ; oxymorphone ER 20 mg q12h in week 1 and 40 mg q12h in week 2 ; oxymorphone ER 20 mg q12h in week 1 and 50 mg q12h in week 2 ; or placebo q12h during weeks 1 and 2 . The primary end point was the change in VAS score for arthritis pain intensity . Other assessment s included the Western Ontario and McMaster Universities ( WOMAC ) OA Index subscales for pain , stiffness , and physical function and the composite index ; the Medical Outcomes Study 36-Item Short-Form Health Survey ( SF-36 ) physical health component summary ( PCS ) score ; the Chronic Pain Sleep Inventory ( CPSI ) score ; vital signs ; clinical laboratory parameters ; and adverse events ( AEs ) . AEs were recorded at each clinic visit . RESULTS Three hundred seventy patients were r and omized to treatment ( 95 oxymorphone ER 10 mg , 93 oxymorphone ER 40 mg , 91 oxymorphone ER 50 mg , and 91 placebo ) , and 198 completed the study . Least squares mean changes from baseline in the VAS arthritis pain intensity score were -21 , -28 , -29 , and -17 mm in the oxymorphone ER 10 , 40 , and 50 mg and placebo groups , respectively ( P = 0.002 , modified Tukey linear trend test ) . Oxymorphone ER 40 and 50 mg produced significant improvements from baseline compared with placebo in the WOMAC subscale scores for pain ( least squares mean change : -85.1 , -108.0 , and -42.5 , respectively ; P < or = 0.025 for 40 mg , P < or = 0.001 for 50 mg ) , stiffness ( -40.5 , -48.1 , and -17.0 ; both , P < or = 0.001 ) , and physical function ( -256.8 , -310.8 , and -116.5 ; P < or = 0.01 and P < or = 0.001 , respectively ) ; the SF-36 PCS score ( 4.6 , 3.6 , and -0.1 ; P < 0.001 ) ; and the CPSI score ( -21.2 , -22.2 , and -10.7 ; P < 0.05 ) . The 10-mg dose also was associated with significant improvements compared with placebo in the WOMAC pain ( -83.6 ; P < or = 0.025 ) and physical function subscales ( -232.9 ; P < or = 0.025 ) and the SF-36 PCS score ( 3.9 ; P < 0.001 ) . The most frequently reported AEs ( > or = 5 % of patients ) in the oxymorphone ER groups were nausea ( 39.4 % ) , vomiting ( 23.7 % ) , dizziness ( 22.6 % ) , constipation ( 22.2 % ) , somnolence ( 17.6 % ) , pruritus ( 16.5 % ) , and headache ( 15.0 % ) . The majority of AEs with oxymorphone ER were mild or moderate in intensity . Three serious AEs ( urinary retention , central nervous system depression , and pancreatitis ) were considered possibly or probably related to study medication . CONCLUSION In these patients with chronic , moderate to severe pain related to OA of the hip or knee , oxymorphone ER administered twice daily for 2 weeks produced dose-related reductions in arthritis pain intensity and improvements in physical function Abstract Background : Tapentadol is a novel , central ly acting analgesic with μ-opioid receptor agonist and norepinephrine reuptake inhibitor activity . Objective : To evaluate the efficacy and safety of tapentadol extended release ( ER ) compared with oxycodone controlled release ( CR ) for management of moderate to severe chronic osteoarthritis-related knee pain . Methods : This was a r and omized , double-blind , active- and placebo-controlled , parallel-arm , multicentre , phase III study during which patients received tapentadol ER , oxycodone CR or placebo for a 3-week titration period followed by a 12-week maintenance period . The study was carried out at sites in Australia , Canada , New Zeal and and the US . A total of 1030 patients with chronic osteoarthritis-related knee pain were r and omized to receive tapentadol ER 100–250 mg twice daily , oxycodone HCl CR 20–50 mg twice daily or placebo . Primary endpoints ( as determined prior to initiation of the study ) were the changes from baseline in average daily pain intensity ( rated by patients on an 11-point numerical rating scale ) over the last week of maintenance and over the entire 12-week maintenance period ; last observation carried forward was used to impute missing values after early treatment discontinuation . Results : Efficacy and safety were evaluated for 1023 patients . Tapentadol ER significantly reduced average pain intensity from baseline to week 12 of the maintenance period versus placebo ( least squares mean [ LSM ] difference [ 95 % CI ] , −0.7 [ −1.04 , −0.33 ] ) , and throughout the maintenance period ( −0.7 [ −1.00 , −0.33 ] ) . Oxycodone CR significantly reduced average pain intensity from baseline throughout the maintenance period versus placebo ( LSM difference [ 95 % CI ] , −0.3 [ −0.67 , −0.00 ] ) but not at week 12 ( −0.3 [ −0.68 , 0.02 ] ) . A significantly higher percentage of patients achieved ≥50 % improvement in pain intensity in the tapentadol ER group ( 32.0 % [ 110/344 ] ) compared with the placebo group ( 24.3 % [ 82/337 ] ; p = 0.027 ) , indicating a clinical ly significant improvement in pain intensity , while a significantly lower percentage of patients achieved ≥50 % improvement in pain intensity in the oxycodone CR group ( 17.3 % [ 59/342 ] ; p = 0.023 vs placebo ) . In the placebo , tapentadol ER and oxycodone CR groups , respectively , 61.1 % ( 206/337 ) , 75.9 % ( 261/344 ) and 87.4 % ( 299/342 ) of patients reported at least one treatment-emergent adverse event ( TEAE ) ; incidences of gastrointestinal-related TEAEs were 26.1 % ( 88/337 ) , 43.0 % ( 148/344 ) and 67.3 % ( 230/342 ) . Conclusion : Treatment with tapentadol ER 100–250 mg twice daily or oxycodone HCl CR 20–50 mg twice daily was effective for the management of moderate to severe chronic osteoarthritis-related knee pain , with substantially lower incidences of gastrointestinal-related TEAEs associated with treatment with tapentadol ER than with oxycodone CR . [ Trial registration number : NCT00421928 ( Clinical Trials.gov Identifier ) CONTEXT Osteoarthritis ( OA ) is a common cause of chronic pain , particularly in the older population . Modern approaches to the management of OA pain recommend tailoring treatment to the individual . This study examines treatment options for OA pain in the form of low-dose transdermal and sublingual opioid analgesia . OBJECTIVES The aims of this trial were to compare the efficacy and tolerability of seven-day , low-dose transdermal buprenorphine patches ( BuTrans , Napp Pharmaceuticals Limited UK ) with sublingual buprenorphine ( Temgesic , Schering-Plough Limited UK ) in patients with moderate to severe pain caused by OA of the hip(s ) and /or knee(s ) , and to establish analgesic equivalence of the two products . METHODS Two hundred forty-six patients with OA pain in the hip(s ) and /or knee(s ) were enrolled in this r and omized , double-blind , parallel-group study ; 110 completed the study . Patients were r and omized to receive transdermal buprenorphine patches ( 5 , 10 , and 20 microg/hour ) or sublingual buprenorphine ( 200 and 400 microg tablets ) . Their medication was titrated to pain control and they were treated for up to seven weeks . The main outcome measures were pain intensity ( primary outcome ) , sleep disturbance , quality of life , and safety assessment s. RESULTS Patients ' Box Scale-11 pain scores decreased between entry and assessment in both treatment groups . During the 28-day assessment period , the estimated mean treatment differences ( 95 % confidence intervals ) were 0.00 ( -0.68,0.69 ) , -0.11 ( -0.85,0.63 ) , and -0.13 ( -0.95,0.68 ) , for the morning , midday , and evening scores , respectively . All the confidence intervals were within the prespecified limits for equivalence ( -1.5 , 1.5 ) . Use of escape medication was low . In both treatment groups , sleep disturbance caused by pain decreased between entry and assessment . Patients ' quality of life improved during the study . Significantly fewer patients receiving the transdermal buprenorphine patches reported nausea ( P=0.035 ) , dizziness ( P=0.026 ) , and vomiting ( P=0.039 ) . CONCLUSION In conclusion , seven-day , low-dose transdermal buprenorphine patches are as effective as sublingual buprenorphine , with a better tolerability profile Introduction Two r and omized , double-blind , placebo-controlled studies in acute and chronic pain treatment , powered to assess noninferiority of the efficacy of tapentadol immediate release ( IR ) ( 50 mg , 75 mg ) versus oxycodone hydrochloride ( HCl ) IR ( 10 mg ) , established comparable efficacy of tapentadol IR with oxycodone HCl IR , and suggested tapentadol IR ’s improved gastrointestinal tolerability . The impact of these equianalgesic doses of tapentadol and oxycodone HCl on bowel function and gastrointestinal tolerability was then directly assessed in the current study , using a vali date d bowel function diary to comprehensively assess opioid-induced constipation symptoms and outcomes . Methods In this double-blind study , patients with end-stage joint disease were r and omized to tapentadol IR ( 50 mg or 75 mg ) , oxycodone HCl IR 10 mg , or placebo . Treatment with IR formulations ( 14 days ) was followed by treatment ( 28 days ) with extended-release ( ER ) formulations of active drugs ( or placebo ) . Results Oxycodone HCl IR treatment significantly decreased ( P<0.001 ) mean ( SD ) number of spontaneous bowel movements over the 14-day period ( average per week : [ 6.7 ( 5.44 ) ] versus tapentadol IR 50 mg [ 9.0 ( 4.04 ) ] , tapentadol IR 75 mg [ 8.6 ( 4.65 ) ] , and placebo [ 9.9 ( 5.16 ) ] ) ( primary measure ) , confirming the tolerability findings of the earlier studies . Additionally , incidences of nausea and vomiting were significantly lower over the 14-day period ( nominal P<0.001 ) for tapentadol IR 50 and 75 mg , versus oxycodone HCl IR 10 mg . Results with ER formulations of tapentadol and oxycodone HCl over a longer treatment period were consistent with those of IR formulations . Conclusion Tapentadol IR ( 50 mg , 75 mg ) consistently demonstrated superior gastrointestinal tolerability , including for the most commonly reported events , such as nausea , vomiting , and constipation at doses that provide comparable efficacy with oxycodone HCl IR 10 mg . These findings vali date and extend the tolerability findings of the two earlier studies that established comparable efficacy of these tapentadol and oxycodone HCl doses Osteoarthritis is estimated to affect 40 million people in the United States and 70 to 90 % of Americans over 75 years of age . Annual costs associated with arthritis ( direct medical expenses and lost wages ) were estimated at $ 95 billion in 2000 , and this cost will increase as its prevalence increases . A number of pharmacologic interventions are used to manage osteoarthritis , including acetaminophen , nonsteroidal anti-inflammatory drugs ( NSAIDs ) , or cyclooxygenase-2 ( COX-2 ) inhibitors as appropriate for mild-to-moderate pain ; tramadol or opioid combinations for moderately severe pain , and opioids for severe pain . Regardless of the pain severity , pharmacologic monotherapy may not be sufficient , and individuals with osteoarthritis pain often require combination therapy . The lidocaine patch 5 % , a targeted peripheral analgesic , has proven efficacy in the treatment of pain secondary to postherpetic neuralgia . It inhibits voltage-gated sodium channels , which may contribute to osteoarthritis pain signaling . Here , we report findings of a pilot open-label trial design ed to assess effectiveness of the lidocaine patch 5 % in patients with osteoarthritis of one or both knees , who had experienced an incomplete response to stable doses of analgesic therapy and to determine if further r and omized controlled trials were warranted OBJECTIVE Low-dose transdermal opioids offer a new therapeutic option for osteoarthritis ( OA ) . This study compared symptom relief obtained with buprenorphine patches plus oral paracetamol with that obtained with an oral codeine-paracetamol combination tablet ( co-codamol ) in older adults with OA . METHOD Two hundred and twenty people ( aged ≥60 years ) with OA hip and /or knee pain were r and omised to treatment with 7-day buprenorphine patches plus oral paracetamol ( 5 - 25 μg/h buprenorphine patches plus 1000 mg oral paracetamol q.i.d . ( 4 times daily ) ; n=110 ) or co-codamol tablets ( two 8/500-two 30/500 mg tablets q.i.d . ; n=110 ) . They entered a titration period of up to 10 weeks , during which their dose of study medication was adjusted until they reached optimum pain control . Patients who achieved optimum pain control entered a 12-week assessment period . The primary outcome was average daily pain scores recorded using the box scale-11 ( BS-11 ) pain scale . RESULTS Both treatments significantly reduced patient pain scores . The estimated treatment difference [ 95 % confidence interval ( CI ) ] was -0.02 ( -0.64 , 0.60 ) for the per protocol ( PP ) population . The results were similar for the full analysis population . Patients receiving 7-day buprenorphine patches plus oral paracetamol needed significantly less escape medication ( ibuprofen ) than those receiving co-codamol tablets ( P=0.002 ; PP population ) . Less than 10 % of patients in the 7-day buprenorphine patches plus oral paracetamol group were receiving the highest dose level at the end of the study , compared with 34 % in the co-codamol group . Withdrawal rates were high in both groups . The incidence of adverse events ( AEs ) was comparable between the groups ( 86.4 % of patients in the 7-day buprenorphine patches plus oral paracetamol group ; 81.7 % in the co-codamol group ) . Six serious AEs were reported in three patients ( 2.7 % ) in the 7-day buprenorphine patches plus oral paracetamol group and one ( 0.9 % ) in the co-codamol group . CONCLUSIONS 7-day buprenorphine patches plus oral paracetamol were non-inferior to co-codamol tablets with respect to analgesic efficacy in older adults with OA pain in the hip/knee & NA ; Efficacy , long‐term effectiveness and safety of opioids in chronic non‐tumor associated pain syndromes ( NTAS ) are still under debate . The study ( MONTAS ) was performed by physicians and psychologists as a multicenter prospect i ve , r and omized , double‐blind placebo‐controlled crossover trial , followed by an open long‐term study . Patients were enrolled only when pain relief from specific defined pretreatment was insufficient . Patients were r and omly assigned to group I receiving sustained‐release morphine ( doses : 20 mg/d titrated appropriately to a maximum of 180 mg/d ) in the first week , placebo in the second week or group II receiving study medication in reverse order . The primary endpoint was defined as : ( i ) adequate pain relief ( pain intensity of less than 50 % of pretreatment intensity or less than 5 on a 11 point Numerical Rating Scale ) and ( ii ) pain rated as tolerable and ( iii ) adverse effects rated as tolerable . Full responders ( all criteria fulfilled under morphine ) and partial responders ( less pain relief , but tolerable side effects ) were offered continuation of treatment with oral morphine in an open long‐term study ( LAMONTAS ) , to be published later . Forty‐nine patients of 997 patients screened fulfilled the inclusion criteria for MONTAS and were enrolled . Mean pain intensity in all patients was reduced by morphine from 7.8 to 5.2 ( NNT : 2.2 ) ; in 17 ( 35.4 % ) responders from 7.4 to 2.9 , in 17 ( 35.4 % ) partial responders from 7.8 to 5.6 and in 14 ( 29.2 % ) non‐responders from 8.2 to 7.7 . Pain reduction correlated with improvement of physical function . Pain disability , depression score , mood and exercise endurance improved , particularly in responders . Gastrointestinal complaints increased , central nervous system‐related complaints were reduced . Efficacy and safety of morphine in NTAS were demonstrated in this r and omized‐controlled trial . Pretreatment failure was the indication for trying morphine treatment ; predictive factors for responsiveness could not be identified The analgesic efficacy and safety of suprofen , 200 mg q.i.d . , and propoxyphene , 65 mg q.i.d . , were compared in 114 patients with chronic pain due to osteoarthritis . Both analgesic agents decreased pain intensity after only 1 week of treatment and considerable pain relief was apparent by week 2 to week 3 of treatment . These beneficial effects persisted with long-term therapy and improvement continued throughout the 24-week treatment period . Overall , the response to suprofen and propoxyphene was good to excellent in most of the patients treated . Long-term administration of suprofen was at least as well tolerated as that of propoxyphene . Only 24 % ( 13 of 55 ) of suprofen-treated patients and 34 % ( 20 of 59 ) of propoxyphene-treated patients discontinued therapy , primarily due to gastrointestinal complaints . It was concluded that suprofen , 200 mg q.i.d . , is comparable in terms of efficacy to propoxyphene , 65 mg q.i.d . , in relieving pain due to osteoarthritis Abstract Objective Patients with osteoarthritis ( OA ) pain often have insufficient pain relief from non-opioid analgesics . The aim of this trial was to study efficacy and tolerability of a low dose 7-day buprenorphine transdermal delivery system , added to a NSAID or coxib regimen , in opioid-naïve patients with moderate to severe OA pain . Methods A 6 months r and omised , double-blind , parallel-group study at 19 centres in Denmark , Finl and , Norway , and Sweden , in which OA patients ( > 40 years ) with at least moderate radiographic OA changes and at least moderate pain in a hip and /or knee while on a NSAID or a coxib were r and omised to a 7-day buprenorphine patch ( n = 100 ) or an identical placebo patch ( n = 99 ) . The initial patch delivered buprenorphine 5 μg/h . This was titrated to 10 or 20 μg/h , as needed . Rescue analgesic was paracetamol 0.5–4 g daily . Statistical analysis of outcome data was mainly with a general linear model , with treatment as factor , the primary joint of osteoarthritis , baseline scores , and season as covariates . Results Most patients had OA-radiographic grade II ( moderate ) or grade III ( severe ) , only 8 in each group had very severe OA ( grade IV ) . The median buprenorphine dose was 10 μg/h . 31 buprenorphine-treated patients and 2 placebo-treated patients withdrew because of side effects . Lack of effect caused 12 placebo-treated and 7 buprenorphine-treated patients to withdraw . The differences in effects between treatments : Daytime pain on movement , recorded every evening on a 0–10 numeric rating scale decreased significantly more ( P = 0.029 ) in the buprenorphine group . Patients ’ Global Impression of Change at the end of the double blind period was significantly improved in the buprenorphine group ( P = 0.017 ) . The chosen primary effect outcome measure , the Western Ontario and McMaster Universities ( WOMAC ) OA Index for Pain ( P = 0.061 ) , and secondary outcome measures , the WOMAC OA score for functional abilities ( P = 0.055 ) , and the WOMAC total score ( P = 0.059 ) indicated more effects from buprenorphine than placebo , but these differences were not statistically significant . In a post-hoc , subgroup analysis with the 16 patients with radiographic grad IV ( very severe ) excluded , WOMAC OA Index for Pain was significantly ( P = 0.039 ) reduced by buprenorphine , compared with placebo . WOMAC OA score for stiffness and the amount of rescue medication taken did not differ . Sleep disturbance , quality of sleep , and quality of life improved in both groups . Side effects : Typical opioid side effects caused withdrawal at a median of 11 days before completing the 168 days double blind trial in 1/3 of the buprenorphine group . Mostly mild local skin reactions occurred equally often ( 1/3 ) in both groups . Conclusions Although the 24 hours WOMAC OsteoArthritis Index of pain was not statistically significantly superior to placebo , day-time movement-related pain and patients ’ global impression of improvement at the end of the 6-months double blind treatment period were significantly better in patients treated with buprenorphine compared with placebo . Opioid side effects caused 1/3 of the buprenorphine- patients to withdraw before the end of the 6-months double blind study period . Implication s A low dose 7-days buprenorphine patch at 5–20 μg/h is a possible means of pain relief in about 2/3 of elderly osteoarthritis patients , in whom pain is opioid-sensitive , surgery is not possible , NSAIDs and coxibs are not recommended , and paracetamol in tolerable doses is not effective enough . Vigilant focus on and management of opioid side effects are essential |
12,855 | 20,091,564 | There is evidence that addition of IFN as maintenance therapy for FL improves progression-free survival .
A net benefit for overall survival is less evident .
In the included studies , IFN was associated with significant toxicities that may have a major impact on a patient 's quality of life | BACKGROUND Indolent non-Hodgkin 's lymphoma , in particular follicular lymphoma ( FL ) , is characterized by multiple remissions and relapses .
Several studies have used interferon-alpha ( IFN ) to control this disease , both as induction and as maintenance therapy .
It is not yet clear whether IFN can be associated with a survival benefit although it may prolong progression-free survival .
OBJECTIVES To determine the effects of IFN in the maintenance therapy of FL . | The purpose of this study was to evaluate the role of interferon as initial and maintenance therapy in patients with newly diagnosed follicular lymphoma . Between 1984 and 1994 , 204 patients with newly diagnosed Stage III or Stage IV follicular lymphoma were r and omized to receive either , Chlorambucil ( CB ) : 10 mg daily for 6 weeks , followed by a 2-week interval , with 3 subsequent 2-week treatment periods at the same dose , separated by 2-week intervals , or , CB given concurrently with interferon ( IFN ) . IFN was given at a dose of 3 × 106units thrice weekly , subcutaneously , throughout the 18-week treatment period . Responding patients were subsequently r and omized to receive maintenance IFN at the dose and schedule described above , or to expectant management . The overall response rate was 161/204 ( 78 % ) , complete remission being achieved in 24 % of patients . Neither the addition of IFN to the initial treatment , nor the use of maintenance IFN influenced response rate , remission duration or survival . This study was undertaken to determine whether IFN , given in combination with , and then subsequent to , CB would alter the clinical course of patients with follicular lymphoma . Disappointingly , this objective was not achieved , no advantage having been demonstrated for the addition of IFN . © 2001 Cancer Research Campaign BACKGROUND Interferon alfa and cytotoxic drugs have synergistic effects in patients with non-Hodgkin 's lymphoma . In 1986 , we design ed a clinical trial to evaluate the benefit of concomitant administration of recombinant interferon alfa with a regimen containing doxorubicin in patients with follicular non-Hodgkin 's lymphoma . METHODS The trial involved 242 patients with advanced low- grade follicular non-Hodgkin 's lymphoma selected on the basis of clinical , radiographic , and biologic criteria . All patients were treated with a regimen consisting of cyclophosphamide , doxorubicin , teniposide , and prednisone ( CHVP ) , given monthly for six cycles and then every two months for one year . After r and omization , 123 patients also received interferon alfa-2b at a dosage of 5 million units three times weekly for 18 months . The remaining 119 patients received chemotherapy alone . RESULTS As compared with the patients treated with CHVP only , the patients treated with CHVP plus interferon alfa had a higher overall rate of response ( 85 percent vs. 69 percent , P = 0.006 ) , a longer median event-free survival ( 34 months vs. 19 months , P < 0.001 ) , and a higher rate of survival at 3 years ( 86 percent vs. 69 percent , P = 0.02 ) . Granulocyte toxicity was greater in the patients treated with CHVP plus interferon alfa than in those treated with CHVP alone . There were no treatment-related deaths . Interferon alfa had to be stopped because of toxic effects ( fatigue and hepatitis ) in 13 patients ( 11 percent ) . CONCLUSIONS The addition of interferon alfa to a regimen containing doxorubicin increased the rate of response , event-free survival , and overall survival in patients with advanced follicular non-Hodgkin 's lymphoma , without serious toxicity , although some patients were unable to tolerate the side effects Since 1985 the combination of chlorambucil ( 10 mg daily , initially for six weeks , then alternating fortnights for 12 weeks ) and interferon-alpha 2b ( Schering-Plough ; 2 x 10(6 ) U/m2 three times weekly by subcutaneous injection for 18 weeks ) has been compared in a r and omised trial with chlorambucil alone in previously untreated patients with stage III or IV follicular lymphoma . Responding patients have subsequently been r and omised to receive maintenance interferon-alpha 2b or no further treatment . Of the 124 treated patients , 108 are evaluable for response with a median follow-up of 30 months . The major toxicity was myelosuppression which was more frequent with chlorambucil and IFN alpha 2b in combination than with chlorambucil alone ( P less than 0.01 ) . There was no treatment-related mortality . Actuarial survival at three years is 75 % for all patients , regardless of therapy . There was no significant difference in response rate according to initial therapy . For the 60 patients achieving a good response to initial therapy who have entered the second part of the trial , there has been a significant prolongation of remission duration in favour of maintenance IFN-alpha 2b ( median not yet reached versus two years for the ' no treatment ' arm , P less than 0.015 ) . Fewest relapses have been seen in patients who received IFN-alpha 2b throughout . Accrual to this trial continues ; this preliminary analysis indicates that maintenance IFN-alpha 2b may extend remission duration in follicular lymphoma PURPOSE To compare progression-free survival ( PFS ) , overall survival ( OS ) , and toxicity of a doxorubicin-containing regimen administered alone or in combination with interferon alfa-2b ( IFNalpha ) in patients with low- grade follicular lymphoma ( FL ) and poor prognostic factors . PATIENTS AND METHODS Two hundred sixty-eight patients with advanced-stage FL received cyclophosphamide , doxorubicin , teniposide , and prednisone ( CHVP ) monthly for 6 months , then every 2 months for 12 months . After r and omization , 242 patients were evaluated for efficacy : 119 received CHVP alone , and 123 also received IFNalpha at a dose of 5 million units three times weekly for 18 months . RESULTS After a 6-year median follow-up , the patients treated with CHVP + IFNalpha showed significantly longer median PFS than those who received CHVP alone ( 2.9 years v 1.5 years , respectively ; P = .0002 ) and significantly longer median OS ( not reached v 5.6 years , respectively ; P = .008 ) . Although some side effects , which included neutropenia , asthenia , fever , elevated serum transaminase levels , flu-like symptoms , and thrombocytopenia , were more frequently observed in patients who received the combination regimen , these reactions were moderate . IFNalpha was withdrawn because of toxicity in 10 % of the patients , and a dosage reduction or temporary suspension was required in 28 % . CONCLUSION With long-term follow-up of 6 years , these results confirm that the addition of IFNalpha to a doxorubicin-containing regimen for patients with advanced-stage and clinical ly aggressive FL not only increased PFS , as in most other similar trials , but also prolonged OS . Toxicity was moderate . The beneficial effects of this combined chemotherapy and IFNalpha regimen on OS probably reflect the selection of FL patients with poor prognostic factors The addition of a brief alpha interferon regimen to each CHOP induction cycle , plus one year of alpha interferon thrice weekly maintenance therapy , has no early effect on response rates or survival in patients with Intermediate or High grade cell NHL . Background : The CHOP ( Cyclophosphamide , Adriamycin , Vincristine , Prednisone ) regimen is the most widely used first-line therapy for patients with Intermediate or High Grade ( IG/HG ) non-Hodgkin 's lymphoma ( NHL ) . Alpha 2b interferon ( INF ) enhances response rates and improves survival in low- grade NHL . The International Oncology Study Group ( IOSG ) conducted a prospect i ve r and omized study comparing CHOP alone or combined with INF in patients with IG/HG-NHL . The primary study aim was to compare the objective response rates in these patient cohorts . Patients and Methods : Patients with a confirmed diagnosis of measurable NHL of International Working Formulation ( IWF ) groups D to H histology were r and omized to receive CHOP alone or CHOP with 5Mu INF SC for 5 days on days 22 to 26 of each 28 day cycle with INF 5 million units ( Mu ) given three times per week sub-cutaneously for 52 weeks in those patients who responded to CHOP plus INF . Results : The overall response rates were equivalent in both groups : CHOP alone ( 214 patients ) 81 % ( complete 55 % , partial 26 % ) ; CHOP plus INF ( 221 patients ) 80 % ( complete 54 % , partial 26 % ) . At 36 months , the actuarial survival rate was equivalent in both groups . Conclusions : There is no apparent early advantage in terms of response or survival conferred by adding the study INF regimen to CHOP therapy for patients with IG/HG-NHL The activity of fludarabine monophosphate ( FLU ) and alpha-interferon ( alpha-IFN ) in low- grade non-Hodgkin 's lymphoma ( LG-NHL ) and B-cell chronic lymphocytic leukemia ( B-CLL ) has been demonstrated in several clinical trials . In a study of 137 previously treated patients , of whom 77 had B-CLL and 60 with LG-NHL , we used FLU as salvage chemotherapy . Dosages of 25 mg/m2 were given in 30-min infusions for 5 consecutive d. Treatment was repeated every 28 d depending on the patient 's clinical status for a maximum of 6 cycles . Entrance to the alpha-IFN maintenance portion of the study depended on patient response to initial FLU . All patients who had obtained a complete or partial response after the FLU therapy were r and omized to receive alpha-IFN or no further therapy . The alpha-IFN dose was 3x10(6 ) units 3 times per wk until disease progression . At 4 yr with a median follow-up of 22 months the percentage of patients with persistent response ranged between 20 % and 30 % among all the responders . Thirty-five ( 45 % ) B-CLL patients achieved major responses ( complete/partial response ) , as did 29 ( 48 % ) of those with LG-NHL . Among the 64 patients who achieved a good response to initial therapy and who have entered the second part of the trial , there has been a rate of prolongation of remission in favour of maintenance alpha-IFN ( p=0.02 ) . FLU therapy is an effective drug inducing remission in pretreated B-CLL and LH-NHL patients . However , as with other therapeutic modalities , remission is rarely maintained beyond 2 yr . So far , maintenance alpha-IFN has not been shown to produce significantly longer remission after treatment with FLU in LG-NHL , and there is no trend towards prolonged remission in B-CLL patients . The role of FLU needs to be further evaluated in the management of lymphoproliferative disorders by introducing it in combination with other drugs ( alpha-IFN ) in the induction phase and in maintenance treatment The past decade has seen the rise of evidence -based medicine , a movement that has focused attention on the importance of using clinical studies for empirical demonstration of the efficacy of medical interventions . Increasingly , physicians are being called on to assess such studies to help them make clinical decisions and underst and the rationale behind recommended practice s. This type of assessment requires an underst and ing of research methods that until recently was not expected of physicians . These research methods include statistical techniques used to assist in drawing conclusions . However , the methods of statistical inference in current use are not evidence -based and thus have contributed to a widespread misperception . The misperception is that absent any consideration of biological plausibility and prior evidence , statistical methods can provide a number that by itself reflects a probability of reaching erroneous conclusions . This belief has damaged the quality of scientific reasoning and discourse , primarily by making it difficult to underst and how the strength of the evidence in a particular study can be related to and combined with the strength of other evidence ( from other laboratory or clinical studies , scientific reasoning , or clinical experience ) . This results in many knowledge cl aims that do not st and the test of time ( 1 , 2 ) . A pair of articles in this issue examines this problem in some depth and proposes a partial solution . In this article , I explore the historical and logical foundations of the dominant school of medical statistics , sometimes referred to as frequentist statistics , which might be described as error-based . I explicate the logical fallacy at the heart of this system and the reason that it maintains such a tenacious hold on the minds of investigators , policymakers , and journal editors . In the second article ( 3 ) , I present an evidence -based approach derived from Bayesian statistical methods , an alternative perspective that has been one of the most active areas of biostatistical development during the past 20 years . Bayesian methods have started to make inroads into medical journals ; Annals , for example , has included a section on Bayesian data interpretation in its Information for Authors section since 1 July 1997 . The perspective on Bayesian methods offered here will differ somewhat from that in previous presentations in other medical journals . It will focus not on the controversial use of these methods in measuring belief but rather on how they measure the weight of quantitative evidence . We will see how reporting an index called the Bayes factor ( which in its simplest form is also called a likelihood ratio ) instead of the P value can facilitate the integration of statistical summaries and biological knowledge and lead to a better underst and ing of the role of scientific judgment in the interpretation of medical research . An Example of the Problem A recent r and omized , controlled trial of hydrocortisone treatment for the chronic fatigue syndrome showed a treatment effect that neared the threshold for statistical significance , P=0.06 ( 4 ) . The discussion section began , hydrocortisone treatment was associated with an improvement in symptoms This is the first such study to demonstrate improvement with a drug treatment of [ the chronic fatigue syndrome ] ( 4 ) . What is remarkable about this paper is how unremarkable it is . It is typical of many medical research reports in that a conclusion based on the findings is stated at the beginning of the discussion . Later in the discussion , such issues as biological mechanism , effect magnitude , and supporting studies are presented . But a conclusion is stated before the actual discussion , as though it is derived directly from the results , a mere linguistic transformation of P=0.06 . This is a natural consequence of a statistical method that has almost eliminated our ability to distinguish between statistical results and scientific conclusions . We will see how this is a natural outgrowth of the P value fallacy . Philosophical Preliminaries To begin our exploration of the P value fallacy , we must consider the basic elements of reasoning . The process that we use to link underlying knowledge to the observed world is called inferential reasoning , of which there are two logical types : deductive inference and inductive inference . In deductive inference , we start with a given hypothesis ( a statement about how nature works ) and predict what we should see if that hypothesis were true . Deduction is objective in the sense that the predictions about what we will see are always true if the hypotheses are true . Its problem is that we can not use it to exp and our knowledge beyond what is in the hypotheses . Inductive inference goes in the reverse direction : On the basis of what we see , we evaluate what hypothesis is most tenable . The concept of evidence is inductive ; it is a measure that reflects back from observations to an underlying truth . The advantage of inductive reasoning is that our conclusions about unobserved states of nature are broader than the observations on which they are based ; that is , we use this reasoning to generate new hypotheses and to learn new things . Its drawback is that we can not be sure that what we conclude about nature is actually true , a conundrum known as the problem of induction ( 5 - 7 ) . From their clinical experience , physicians are acutely aware of the subtle but critical difference between these two perspectives . Enumerating the frequency of symptoms ( observations ) given the known presence of a disease ( hypothesis ) is a deductive process and can be done by a medical student with a good medical textbook ( Figure 1 , top ) . Much harder is the inductive art of differential diagnosis : specifying the likelihood of different diseases on the basis of a patient 's signs , symptoms , and laboratory results . The deductions are more certain and objective but less useful than the inductions . Figure 1 . The parallels between the processes of induction and deduction in medical inference ( top ) and statistical inference ( bottom ) . The identical issue arises in statistics . Under the assumption that two treatments are the same ( that is , the hypothesis of no difference in efficacy is true ) , it is easy to calculate deductively the frequency of all possible outcomes that we could observe in a study ( Figure 1 , bottom ) . But once we observe a particular outcome , as in the result of a clinical trial , it is not easy to answer the more important inductive question , How likely is it that the treatments are equivalent ? In this century , philosophers have grappled with the problem of induction and have tried to solve or evade it in several ways . Karl Popper ( 8) proposed a philosophy of scientific practice that eliminated formal induction completely and used only the deductive elements of science : the prediction and falsification components . Rudolf Carnap tried an opposite strategy to make the inductive component as logically secure as the deductive part ( 9 , 10 ) . Both were unsuccessful in producing workable models for how science could be conducted , and their failures showed that there is no method ologic solution to the problem of fallible scientific knowledge . Determining which underlying truth is most likely on the basis of the data is a problem in inverse probability , or inductive inference , that was solved quantitatively more than 200 years ago by the Reverend Thomas Bayes . He withheld his discovery , now known as Bayes theorem ; it was not divulged until 1762 , 20 years after his death ( 11 ) . Figure 2 shows Bayes theorem in words . Figure 2 . Bayes theorem , in words . As a mathematical equation , Bayes theorem is not controversial ; it serves as the foundation for analyzing games of chance and medical screening tests . However , as a model for how we should think scientifically , it is criticized because it requires assigning a prior probability to the truth of an idea , a number whose objective scientific meaning is unclear ( 7 , 10 , 12 ) . It is speculated that this may be why Reverend Bayes chose the more dire of the publish or perish options . It is also the reason why this approach has been tarred with the subjective label and has not generally been used by medical research ers . Conventional ( Frequentist ) Statistical Inference Because of the subjectivity of the prior probabilities used in Bayes theorem , scientists in the 1920s and 1930s tried to develop alternative approaches to statistical inference that used only deductive probabilities , calculated with mathematical formulas that described ( under certain assumptions ) the frequency of all possible experimental outcomes if an experiment were repeated many times ( 10 ) . Methods based on this frequentist view of probability included an index to measure the strength of evidence called the P value , proposed by R.A. Fisher in the 1920s ( 13 ) , and a method for choosing between hypotheses , called a hypothesis test , developed in the early 1930s by the mathematical statisticians Jerzy Neyman and Egon Pearson ( 14 ) . These two methods were incompatible but have become so intertwined that they are mistakenly regarded as part of a single , coherent approach to statistical inference ( 6 , 15 , 16 ) . The P Value The P value is defined as the probability , under the assumption of no effect or no difference ( the null hypothesis ) , of obtaining a result equal to or more extreme than what was actually observed ( Figure 3 ) . Fisher proposed it as an informal index to be used as a measure of discrepancy between the data and the null hypothesis . It was not part of a formal inferential method . Fisher suggested that it be used as part of the fluid , non-quantifiable process of drawing conclusions from observations , a process that included combining the P value in some unspecified way with background information ( 17 ) . Figure 3 . The bell-shaped curve represents the probability of every possible outcome under the null hypothesis . P P It is worth noting one widely The FL2000 study was undertaken to evaluate the combination of the anti-CD20 monoclonal antibody rituximab with chemotherapy plus interferon in the first-line treatment of follicular lymphoma patients with a high tumor burden . Patients were r and omly assigned to receive either 12 courses of the chemotherapy regimen CHVP ( cyclophosphamide , adriamycin , etoposide , and prednisolone ) plus interferon-alpha2a ( CHVP+I arm ) over 18 months or 6 courses of the same chemotherapy regimen combined with 6 infusions of 375 mg/m(2 ) rituximab and interferon for the same time period ( R-CHVP+I arm ) . After a median follow-up of 5 years , event-free survival estimates were , respectively , 37 % ( 95 % confidence interval [ CI ] , 29%-44 % ) and 53 % ( 95 % CI , 45%-60 % ) in the CHVP+I and R-CHVP+I arm ( P = .001 ) . Five-year overall survival estimates were not statistically different in the CHVP+I ( 79 % ; 95 % CI , 72%-84 % ) and R-CHVP+I ( 84 % ; 95 % CI , 78%-84 % ) arms . In a multivariate regression analysis , event-free survival was significantly influenced by both the Follicular Lymphoma International Prognostic Index score ( hazard ratio = 2.08 ; 95 % CI , 1.6%-2.8 % ) and the treatment arm ( hazard ratio = 0.59 ; 95 % CI , 0.44%-0.78 % ) . With a 5-year follow-up , the combination of rituximab with CHVP+I provides superior disease control in follicular lymphoma patients despite a shorter duration of chemotherapy . This study 's clinical trial was registered at the National Institutes of Health website as no. NCT00136552 The Eastern Cooperative Oncology Group ( ECOG ) performed a prospect ively r and omized study ( E6484 ) evaluating the use of interferon alfa 2a ( IFN-α2a ) in patients with aggressive low- grade or with intermediate- grade non-Hodgkin 's lymphoma ( NHL ) accruing close to 300 patients between 1985 and 1988 . Patients were eligible for study if they had bulky or symptomatic low- grade lymphoma or defined intermediate- grade subtypes . Of 291 patients enrolled , 249 were eligible for analysis . All patients were r and omized to receive a four-drug cytotoxic chemotherapy regimen including cyclophosphamide , doxorubicin , vincristine and prednisone in 4-week cycles with or without IFN-α2a in addition ( COPA vs I-COPA ) . Treatment was given for up to 8–10 months . This report , at a time when the median follow-up among survivors has reached 12 years , up date s the analysis of time to treatment failure ( TTF ) , duration of disease-free survival ( DFS ) , and overall survival . Patients r and omized to receive IFN-α2a had a prolonged TTF ( P = 0.008 ; median 2.4 vs 1.6 years ) . DFS for those patients who had complete responses was also longer if IFN-α2a had been given ( P = 0.035 ; median 2.7 vs 1.8 years ) . There was a clinical ly but not a statistically significant prolongation of overall survival by IFN-α2a ( P = 0.107 ; median 7.8 vs 5.7 years ) . There were fewer deaths over time due to lymphoma in patients receiving IFN-α2a ( 67 vs 80 deaths ) . A subset analysis , based on disease histology ( low- grade , follicular , intermediate- grade ) , revealed a significant prolongation of TTF in patients receiving IFN-α2a with either low- grade ( P = 0.002 ; median 2.4 vs 1.6 years ) or follicular ( P = 0.01 ; median 2.5 vs 1.7 years ) NHL but not intermediate grade ( P = 0.622 ; median 2.3 vs 1.6 years ) NHL . This analysis , performed approximately 12 years after closure of the study to accrual , supports the addition of interferon alfa to an induction cytotoxic chemotherapy regimen including cyclophosphamide and doxorubicin in the treatment of follicular NHL Alpha interferon has shown initial promise in the treatment of low- grade non-Hodgkin 's lymphoma ( NHL ) , especially with the nodular form of the disease . The present study enrolled 70 NHL patients who received either chlorambucil ( CB ; 10 mg/day ) or CB plus interferon alfa-2b ( 5 million units (MU)/m2 subcutaneously three times a week ) . Among 63 evaluable patients , similar response rates ( 62.1 % and 64.7 % respectively ) were recorded for the treatment arms . In patients receiving no maintenance therapy , those who received interferon alfa-2b during the induction phase showed a favourable trend in terms of incidence of relapse compared to those who had received chlorambucil alone . During maintenance therapy with interferon alfa-2b , no significant differences in the occurrence of relapse have yet been seen compared to patients on no maintenance therapy . A longer observation period is needed to make a definitive conclusion about the usefulness of interferon maintenance therapy and to evaluate further the effects of the combined schedule of chlorambucil and interferon induction on the duration of remission Summary Twenty-two patients with non-Hodgkin 's lymphoma ( NHL ) were treated with a combined regimen of interferon alfa-2b ( Intron A ; Schering-Plough ) and chlorambucil to evaluate the response and efficacy in pre-treated or relapsed patients . Ten patients were classified as having follicular lymphoma and 12 diffuse lymphoma . The treatment schedule consisted of interferon alfa-2b 3 × 106 IU/m2 thrice-weekly and chlorambucil 10 mg daily for three weeks , with a week 's rest between each cycle . Treatment continued for upto six cycles . We obtained two complete remissions ( CR ) , 12 good partial remissions ( GPR ) , seven no remissions ( NR ) and one stable disease . On histologic examination we observed a response in 8 of 10 patients with follicular lymphoma ( 2 CR and 6 GPR ) ; three of five patients with diffuse mixed lymphoma , and three of seven patients with diffuse lymphoma showed GPR.The major toxicity consisted of fever and nausea and , in one case , lethargy . In one patient the treatment was stopped at the second cycle because of poor compliance . Hematologic toxicity was generally mild and occurred between the third and fourth cycle . We observed hepatic toxicity i.e. a transient increase of transaminase levels , in three patients .We consider this regimen to be effective in the treatment of relapsed or resistant NHL and no more toxic than single agent therapy . A r and omized study to verify this therapeutic approach versus conventional therapy with chlorambucil alone in first-line treatment is recommended PURPOSE To compare mantle-cell lymphomas ( MCLs ) and follicle-center lymphomas ( FCLs ) for their features of clinical presentation , response to chemotherapy , and prognosis on the basis of a prospect i ve r and omized clinical trial . PATIENTS AND METHODS Patients with MCL and FCL who entered onto the prospect i ve r and omized comparison of cyclophosphamide , vincristine , and prednisone ( COP ) versus prednimustine and mitoxantrone ( PmM ) followed by a second r and omization for interferon ( IFN ) maintenance versus observation only . RESULTS One hundred sixty-five of 234 patients had FCL and 45 of 234 patients had MCL . With FCL , both sexes were equally affected ( men , 47 % ) ; patients with MCL were predominantly men ( 78 % ; P < .0004 ) and had a higher median age ( 64 v 53 years ; P < .0001 ) . Patients with MCL also had more widespread disease , reflected by the proportion of patients with two or greater extranodal manifestations ( 43 % v 21 % ; P < .005 ) and nine or greater involved nodal areas ( 64 % v 45 % ; nonsignificant [ NS ] ) . Response to chemotherapy was significantly lower in patients with MCL ( complete remission [ CR ] + partial remission [ PR ] , 69 % v 88 % ; P < .05 ) and occurred at a slower pace . Patients with MCL also had a shorter event-free interval ( median , 8 v 24 months ; P < .0001 ) and overall survival ( median , 28 v 77 months ; P < .0001 ) . In both subtypes , however , patients with less than two residual lymphoma manifestations in remission experienced a relatively good prognosis with an estimated 5-year survival of greater than 60 % for MCL and greater than 75 % for FCL . CONCLUSION MCL and FCL differ substantially in their features of presentation , response to chemotherapy , and long-term prognosis . The extent of residual disease after completion of chemotherapy discriminates patients with different prognosis and may be used for the stratification of postremission strategies Rituximab and IFN have each demonstrated single-agent activity in patients with low- grade non-Hodgkin 's lymphoma ( NHL ) . A single-arm , multicenter , Phase II trial was conducted to assess the safety and efficacy of combination therapy with rituximab and IFN-alpha-2a in 38 patients with relapsed or refractory , low- grade or follicular , B-cell NHL . IFN-alpha-2a [ 2.5 or 5 million units ( MIU ) ] was administered s.c . , three times weekly for 12 weeks . Starting on the fifth week of treatment , rituximab was administered by i.v . infusion ( 375 mg/m2 ) weekly for 4 doses . All 38 patients received four complete infusions of rituximab and were evaluable for efficacy , although 11 patients ( 29 % ) did not-receive all 36 injections of IFN . The mean number of IFN-alpha-2a injections was 31 doses ; the mean total units received were 141 MIU ( maximum , 180 MIU ) . The study treatment was reasonably well tolerated with no unexpected toxicities stemming from the combination therapy . No grade 4 events were reported . Frequent adverse events during the treatment period included asthenia ( 35 of 38 patients ) , chills ( 31 of 38 ) , fever ( 30 of 38 ) , headache ( 28 of 38 ) , nausea ( 23 of 38 ) , and myalgia ( 22 of 38 ) . The overall response rate was 45 % ( 17 of 38 patients ) ; 11 % had a complete response , and 34 % had a partial response . The Kaplan-Meier estimates for the median response duration and the median time to progression in responders are 22.3 and 25.2 months , respectively . Further follow-up is needed to determine whether this treatment combination leads to a significantly longer time to progression than single-agent treatment with rituximab PURPOSE To evaluate prospect ively in patients with follicular lymphoma and a low tumor burden three therapeutic options : delay of any treatment until clinical ly meaningful progression , immediate treatment with an oral alkylating agent , or treatment with a biologic response modifier , interferon alfa-2b . PATIENTS AND METHODS Newly diagnosed follicular lymphoma patients with a low tumor burden ( n = 193 ) were r and omly assigned to one of three arms : arm 1 , no initial treatment ( n = 66 ) ; arm 2 , prednimustine 200 mg/m2/d for 5 days per month for 18 months ( n = 64 ) ; or arm 3 , interferon alfa 5 MU/d for 3 months then 5 MU three times per week for 15 months ( n = 63 ) . Clinical characteristics were similar in the three arms . RESULTS Overall response rates with prednimustine and interferon alfa were 78 % and 70 % , respectively . The overall response to therapy , when deferred , was similar at 70 % . With a median follow-up duration of 45 months after r and omization , the median freedom-from-treatment ( FFT ) interval was 24 months in arm 1 and the interval of freedom from treatment failure ( FFTF ) was 40 months in arm 2 and 35 months in arm 3 . The median overall survival time was not reached and the overall survival rate at 5 years was 78 % in arm 1 , 70 % in arm 2 , and 84 % in arm 3 . Therefore , deferred treatment does not adversely influence survival at 5 years . Patients who progressed within 1 year had a significantly shorter survival duration ( median , 48 months ) . CONCLUSION Delayed treatment is feasible in patients with follicular lymphoma and a low tumor burden . For patients with early progression , more intensive therapy should be considered . For others , because delay of treatment until significant clinical progression does not seem to hamper the prognosis or subsequent response to treatment , the long-term toxicity of alkylating agents can be reduced PURPOSE The treatment of patients with follicular lymphoma has changed with the introduction of high-dose therapy ( HDT ) with autologous stem-cell transplant then with rituximab . The effect of these two strategies on the outcome of relapsing patients with follicular lymphoma has never been compared . PATIENTS AND METHODS We analyzed two cohorts of patients treated in two successive r and omized studies with the same treatment , cyclophosphamide , doxorubicin , teniposide , and prednisolone plus interferon , to evaluate the role of rituximab and HDT in salvage therapy after first disease progression or relapse . RESULTS Of the 364 patients included in these two studies , 254 progressed or relapsed and constitute the population of this analysis . Among them , 98 had been treated with HDT , including 33 of them after rituximab-containing salvage regimen , and 69 with rituximab alone or combined with chemotherapy but without HDT . Patients ' characteristics at diagnosis were similar in all subgroups . If event-free survival was identical for patients treated within Groupe d'Etude des Lymphomes Folliculaires ( GELF ) -86 or GELF-94 studies , overall survival was longer in GELF-94 study . HDT was associated with a statistically significant benefit in terms of event-free survival from relapse and survival after relapse ( SAR ) . Rituximab was associated with a greater benefit than HDT for these two end points . When both treatments were combined , patients treated with rituximab-containing salvage regimen followed by HDT had 5-year SAR more than 90 % . CONCLUSION In follicular lymphoma , for patients treated with first-line chemotherapy the combination of a salvage regimen containing rituximab with or without HDT leads to a dramatic improvement of long-term outcome BACKGROUND Interferon alfa has been found to be effective as an antitumor agent ( with a response rate of 30 percent ) in patients with low- grade non-Hodgkin 's lymphoma , but its effectiveness in those with intermediate- grade non-Hodgkin 's lymphoma has been less adequately tested . In a prospect i ve r and omized study we evaluated the effectiveness of adding interferon alfa to cytotoxic chemotherapy in patients with clinical ly aggressive , low- grade non-Hodgkin 's lymphoma and certain histologic variants of intermediate- grade non-Hodgkin 's lymphoma , not including diffuse histiocytic lymphoma . METHODS The patients were r and omly assigned to a regimen of cyclophosphamide , vincristine , prednisone , and doxorubicin or to this regimen combined with recombinant interferon alfa . Treatment was administered every four weeks , for 8 to 10 cycles . RESULTS The two regimens produced comparable objective responses , but the regimen including interferon had a greater effect in prolonging the time to treatment failure ( P < 0.001 ) and the duration of complete response ( P = 0.03 ) . Interferon alfa also had a greater effect on overall survival ( P = 0.014 ) when the results were adjusted for important covariates . CONCLUSIONS Interferon alfa , when added to a four-drug doxorubicin-based chemotherapy regimen , is an effective antitumor agent in patients with clinical ly aggressive low- grade or intermediate- grade non-Hodgkin 's lymphoma PURPOSE Interferon alfa has shown significant activity in patients with low- grade malignant non-Hodgkin 's lymphoma ( NHL ) . In 1985 , we initiated a prospect i ve r and omized study in which the potential benefit of interferon alfa given as maintenance treatment was investigated after tumor load reduction was achieved with chemoradiotherapy in patients with advanced low- grade malignant non-Hodgkin 's lymphoma . PATIENTS AND METHODS The study involved 347 patients with stage III or IV disease , 315 satisfying the eligibility criteria . All were treated with a regimen of cyclophosphamide , vincristine , and prednisone ( CVP ) given every 3 weeks for eight cycles . Thereafter , patients were eligible for iceberg irradiation . Finally , all patients were completely restaged , and responding and stable-disease patients were then r and omized , 122 to interferon alfa-2a maintenance , 3 million U three times weekly for 1 year ; and 120 to no further treatment . RESULTS Seventy-nine percent of the patients response to CVP , ie , 45 % complete remissions ( CR ) and 34 % partial remissions ( PR ) . In the group of r and omized patients , the response rate after CVP plus or minus radiotherapy was 90 % . As compared with control patients , patients in the interferon ( IFN ) maintenance group had a tendency toward a prolonged time to progression ( TTP ) ( median , 132 v 87 weeks ; P = .054 , adjusted for response to CVP ) . However , overall survival was similar in both groups . Interferon was well tolerated . The median dose of IFN actually received corresponded to 90 % of the planned cumulative dose . The treatment had to be stopped because of toxicity in 16 patients ( 15 % of the patients in whom IFN was started ) . CONCLUSION Interferon maintenance treatment in the phase of minimal residual disease of patients with advanced low- grade malignant NHL increased TTP at the borderline of statistical significance , without remarkable toxicity . However , overall survival was not influenced The best treatment of follicular lymphoma remains to be determined because the long natural history of follicular lymphoma requires mature data for accurate analysis . Although the goal of primary treatment remains durable remission , the sequential application of effective treatments may also result in a prolongation of median survival time . The use of interferon ( IFN ) with doxorubicin-based chemotherapy has demonstrated an increase of event-free survival but not in overall survival ; however , its acute and late cardiac toxicity limits its use . For this reason , we began a controlled clinical trial to assess the efficacy and toxicity of chemotherapy : COPP ( cyclophosphamide , vincristine , prednisone , and procarbazine ) + IFN alternating every month for six cycles compared to six cycles of chemotherapy . In an intent-to treat analysis , 55 patients were enrolled ( median age 61 years ) . Most cases ( 91 % ) with advanced disease were r and omly assigned to chemotherapy + IFN ( 28 cases ) or chemotherapy ( 27 cases ) . Complete remission was observed in 16 patients : 59 % ( 95 % CI , 53 - 70 % ) in the chemotherapy arm compared to 20 patients 71 % ( 95 % CI , 58 - 79 % ) in the chemotherapy + IFN arm ; total responses were 74 % and 86 % , respectively . At a median follow-up of 60 months , event-free survival was 100 % for patients treated with chemotherapy + IFN , which was statistically different from patients treated with chemotherapy 70 % . At 7 years , median survival has not yet been reached ; 72 % of patients chemotherapy + IFN remain alive without disease ( 95 % CI , 59 - 81 % ) , which is not statistically different from 72 % ( 95%CI , 50 - 73 % ) in the chemotherapy arm . Non-hematological toxicity was most frequent and severe in the chemotherapy arm ; hematological toxicity was similar in both groups . Thus , it appears that chemotherapy + IFN , as described herein , improves event-free survival but the overall survival rates remain unchanged . The use of COPP appears to be better that anthracycline-based chemotherapy because it avoids the presence of acute and late cardiac toxicity We assessed the efficacy and toxicity of interferon alpha 2b ( IFN ) as maintenance therapy in patients with low grade malignant lymphoma . Between March 1986 and December 1989 , 98 patients with low- grade malignant lymphoma in complete remission after conventional chemotherapy were r and omly assigned to received IFN , 5.0 MU three times a week for one year , as maintenance therapy ( n = 48 ) , or to receive no treatment ( control group , n = 50 ) . In March 1994 , the median duration of response had not yet been reached in the patients treated with IFN compared to 46 months in the control group . At 9-years 62 % of the patients in the IFN arm remain in first complete remission compared to only 25 % in the control group ( p < .001 ) . In addition , the median duration of survival has not yet been reached in either the IFN arm compared to 74 months in the control group ( p < .001 ) . Quality of life was excellent in both groups and severe side effects secondary to IFN treatment were not observed . All patients completed the planned dose of IFN . We conclude that IFN as maintenance therapy in low- grade malignant lymphoma is an excellent therapeutic option because it improves the duration of remission and survival without producing severe side effects or reducing the quality of life PURPOSE Rituximab has been shown to be active in follicular lymphoma ( FL ) , both as monotherapy and in combination with chemotherapy . We conducted a r and omized trial comparing mitoxantrone , chlorambucil , and prednisolone ( MCP ) chemotherapy plus rituximab with MCP alone . PATIENTS AND METHODS Previously untreated patients with stage III or IV CD20 + indolent or mantle cell lymphoma were r and omly assigned to either eight 28-day cycles of MCP plus rituximab ( R-MCP ; n = 181 ) or eight cycles of MCP alone ( n = 177 ) . All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse . Herein , we report the results from the primary analysis population of patients with FL , who constituted the majority of patients ( 56 % ) recruited to the trial ( n = 201 ; R-MCP , n = 105 ; MCP , n = 96 ) . RESULTS Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm ( overall response , 92 % v 75 % , respectively ; P = .0009 ; complete response , 50 % v 25 % , respectively ; P = .004 ) . With a median follow-up time of 47 months , median event-free survival ( EFS ) and progression-free survival ( PFS ) times were significantly prolonged with R-MCP compared with MCP ( EFS , not reached v 26 months , respectively ; P < .0001 ; PFS , not reached v 28.8 months , respectively ; P < .0001 ) , and overall survival ( OS ) was significantly improved with R-MCP compared with MCP ( 4-year OS rate , 87 % v 74 % , respectively ; P = .0096 ) . CONCLUSION The R-MCP regimen significantly improves complete and overall response rates , EFS , PFS , and OS in patients with previously untreated advanced FL , without a clinical ly significant increase in toxicity PURPOSE S8809 is a r and omized phase III trial determining whether intensive cytoreductive treatment , followed by interferon consolidation at the time of minimal residual disease , prolongs the progression-free survival ( PFS ) or overall survival ( OS ) of indolent lymphoma patients . PATIENTS AND METHODS Five hundred seventy-one patients with previously untreated stage III or IV low- grade non-Hodgkin 's lymphoma were registered . Patients received six to eight cycles of prednisone , methotrexate , doxorubicin , cyclophosphamide , and etoposide/mechlorethamine , vincristine , procarbazine , and prednisone ( ProMACE[day 1]-MOPP[day 8 ] ) chemotherapy or chemotherapy plus radiotherapy . Responding patients were r and omized to observation alone or to interferon consolidation . Interferon alpha-2b 2 mU/m(2 ) was given subcutaneously three times weekly for 2 years . RESULTS Two hundred sixty-eight eligible patients were r and omized to interferon alpha consolidation ( n = 144 ) or observation alone ( n = 124 ) . With a median follow-up time from r and omization among patients still alive of 6.2 years , the median PFS time was 4.1 years for patients who received interferon consolidation therapy and 3.2 years for patients who were observed after ProMACE-MOPP induction ( P = .25 ) . The adjusted hazard ratio for relapse for observation to interferon was 0.83 ( 95 % confidence interval [ CI ] , 0.61 to 1.13 ) . The median OS has not been reached in either group . At 5 years , OS is 78 % for the interferon group and 77 % for the observation group ( P = .65 ) . The adjusted hazard ratio for survival for observation to interferon is 1.11 ( 95 % CI , 0.69 to 1 . 79 ) . CONCLUSION Interferon alpha consolidation therapy after intensive treatment with anthracycline-containing combination chemotherapy and involved-field radiation therapy does not prolong the PFS or OS of patients with low- grade non-Hodgkin 's lymphoma PURPOSE We review ed survival data of patients with low- grade lymphoma entered on Southwest Oncology Group ( SWOG ) lymphoma trials in 1972 to 1983 to determine the utility of doxorubicin-containing therapy ( cyclophosphamide , doxorubicin , vincristine , and prednisone [ CHOP ] ) in such patients . PATIENTS AND METHODS We identified all patients with low- grade lymphoma , no prior therapy , and stage III or IV disease who were treated with full-dose CHOP induction therapy on any arm of SWOG studies 7204 , 7426 , or 7713 . Survival data for this group of patients were correlated with pretreatment prognostic factors , including histology , patient age , sex , symptom status , performance status , bone marrow or extranodal involvement , and the number of disease sites . The effect of maintenance treatment was also assessed . RESULTS Four hundred fifteen patients met criteria for inclusion in the study group . With median follow-up periods of 12.8 years ( maximum , 19.8 years ) , the median survival duration was 6.9 years . Survival was significantly shorter in patients with follicular mixed or small lymphocytic histology , age greater than 40 years , male sex , B-symptom status , and SWOG performance status greater than 1 . Multivariate regression analysis showed histology , age , and sex to be independent predictors of survival . There was no definite survival plateau of cured patients in any subgroup , although the survival curve for follicular mixed histology patients showed long-term survival of approximately 25 % . Maintenance therapy did not prolong survival . CONCLUSION Doxorubicin-containing treatment did not prolong the overall median survival of low- grade lymphoma patients compared with results with less-aggressive programs BACKGROUND Ninety percent of low- grade follicular lymphomas ( FLs ) carry the t(14;18 ) translocation . This event juxtaposes the bcl-2 oncogene to the immunoglobulin ( Ig ) heavy-chain gene and leads to bcl-2 gene overexpression . Morphologic transformation of FL to high- grade lymphoma is associated with multiple secondary chromosomal abnormalities of the neoplastic cells . DESIGN To analyze whether additional structural alterations of the translocated bcl-2 gene are associated with morphologic transformation of FL , we PCR-amplified , cloned , and sequenced the major breakpoint region ( MBR ) and the open reading frames ( ORF ) of the translocated bcl-2 oncogene in six paired sample s of FL and subsequent diffuse large-cell lymphoma ( DLL ) . RESULTS In five cases , FL and DLL cells were clonally related , as suggested by the identical MBR sequences , but in one case they were different . PCR single-str and conformation polymorphism ( SSCP ) and sequence analyses were performed for identification of structural alterations of the bcl-2 gene in the OFR region corresponding to the 239 amino acid p26-bcl-2a protein . In three of the six patients , a total of 11 point mutations of the ORF were detected in the DLL cells . Four of them , at positions 29 , 46 , 59 , and 106 , yielded amino acid replacements . CONCLUSIONS These findings demonstrate that FL and DLL cells may be clonally related or unrelated . They also show that transformation of FL cells can be associated with somatic point mutations of the bcl-2 oncogene ORF sequence result ing in alteration of the p26-bcl-2a gene product PURPOSE To evaluate the effectiveness of adding interferon ( IFN ) alfa-2b to chemotherapy in the induction treatment of low- grade non-Hodgkin 's lymphoma ( NHL ) , and to assess the role of maintenance IFN . PATIENTS AND METHODS A multicenter , two-phase controlled trial with double r and omization was conducted in 155 patients with low- grade NHL . In the first r and omization , 78 patients received cyclophosphamide , vincristine , and prednisone ( CVP ) and IFN , 3 MU/m2 three times a week for 3 months , and 77 patients received CVP alone . Responding patients were r and omized to receive IFN for 1 year versus observation . RESULTS Of 144 assessable patients , 73 received CVP + IFN and 71 received CVP . Responses were similar : CVP + IFN 79 % versus CVP 76 % ( P = .62 ) . The number of patients who did not complete the treatment was higher in the CVP + IFN group than in the CVP group ( 18 % v 4 % ; P = .009 ) , although the received dose-intensity of chemotherapy was comparable . Duration of response and progression-free survival ( PFS ) were significantly higher in the CVP + IFN group than in the CVP group ( P = .0004 ) . However , we observed no differences in overall survival ( OS ) ( P = .30 ) , with a median follow-up for the surviving patients of 3 years . Grade 3/4 granulocytopenia was the most frequent toxicity and was similar in both groups ( 33 % v32 % ) . Eighty-three ( 74 % ) of the 112 responding patients were r and omized to maintenance IFN or observation . The duration of response was similar between 42 patients that received IFN compared with 41 control patients ( P = .83 ) , independently of treatment previously administered . CONCLUSION Adding IFN alfa-2b to induction CVP in low- grade NHL did not induce a higher response rate , but it significantly increased the duration of the responses . We found significant differences in PFS that favored the patients who received CVP + IFN , but not in OS . To date , no additional benefit has been seen from the administration of IFN for maintenance The role of interferon alpha as maintenance therapy in follicular lymphoma ( FL ) remains unsolved . We started a controlled clinical trial to assess if interferon alpha 2b could improve outcome , measured with event free survival ( EFS ) and overall survival ( OS ) in patients with FL in complete remission after chemotherapy based anthracyclines and adjuvant radiotherapy to sites of initial bulky disease . Three hundred and eighty four patients in complete response after 6 cycles of CEOP-Bleo ( cyclophosphamide , epirubicin , vincristine , prednisone and bleomycin , at st and ard doses ) , and adjuvant radiotherapy when necessary , were r and omized to received Interferon alpha 2b , three times a week for 1 year or no treatment ( control group ) . Median follow up was 9.8 years ( range 7.0 - 15 years ) ; actuarial curves showed that EFS was 64 % ( 95 % confidence interval ( CI ) 56 - 71 % ) in patients treated with interferon that was statistically significant to patients in the control group : 35 % ( 95 % CI : 28 - 43 % ) ( p < .01 ) . OS was also statistically significant : 81 % in patients treated with interferon ( 95 % CI : 74 - 93 % ) and 57 % ( 95 % CI : 50 - 63 % ) in the control group ( p < .001 ) . Toxicity was mild , all patients received the planned dose of interferon on time . The use of aggressive chemotherapy and maintenance therapy with interferon alpha 2b in follicular lymphoma improved outcome ; more than 60 % of patients remain alive free of disease at longer follow-up The current study was initiated to compare the anti-lymphoma activity and side-effects of prednimustine/mitoxantrone ( PmM ) vs cyclophosphamide , vincristine , prednisone ( COP ) in patients with advanced low- grade non-Hodgkin 's lymphomas in way of a prospect i ve r and omized multicenter trial . Two hundred and forty-six patients with stage III or IV centroblastic-centrocytic ( CB-CC ( Kiel-classification ) ) or follicle center lymphoma ( FCL ( REAL classification ) ) and centrocytic ( CC ) or mantle-cell-lymphoma ( MCL ) were r and omized for therapy with either PmM or COP and are fully evaluable for response and toxicity . PmM consisted of prednimustine 100 mg/m2/day on days 1 - 5 and mitoxantrone 8 mg/m2 /day days 1 and 2 , while COP comprised cyclophosphamide 400 mg/m2/day on days 1 - 5 , vincristine 1.4 mg/m2/day on day 1 and prednisone 100 mg/m2/day on days 1 - 5 . Both regimens were repeated for a total of six cycles followed by an additional two courses for consolidation in responding cases and a subsequent second r and omization for interferon alpha maintenance vs observation only . Overall response rates were comparable with 83 % complete and partial remissions after COP and 84 % remissions after PmM. PmM revealed a significantly higher rate of complete remissions ( 36 vs 18 % , P < 0.006 ) , the majority being achieved after four courses . The more rapid and possibly also more effective reduction of the lymphoma cell mass by PmM result ed in a tendency to a longer event-free interval for patients achieving remissions after PmM as compared to COP with estimated median event-free intervals of 31 vs 14 months , respectively ( P=0.04 ) . Separate analysis of lymphoma subtypes showed a tendency to a lower rate of complete remission in CC or MCL as compared to CB-CC or FCL ( 16 vs 30 % , P=0.12 , NS ) while overall response rates were in a similar range ( 81 vs 85 % ) . In both subtypes , PmM induced a higher rate of complete remission while overall response rates were comparable after PmM or COP . Treatment associated side-effects comprised predominantly myelosuppression and granulocytopenia in particular which was more frequently observed after PmM than COP ( 43 vs 31 % , P < 0.0001 ) . This difference was clinical ly irrelevant , however , since serious infectious complications were encountered in less than 3 % of cycles after both regimens . COP therapy was associated with a significantly higher incidence and degree of hair loss and complete alopecia ( 31 vs 2 % ) as well as of peripheral neurotoxicity ( 23 vs 2 % ) . These data show that both PmM and COP reveal a high anti-lymphoma activity in patients with advanced stage non-Hodgkin 's lymphoma . PmM appears advantageous with a higher rate of complete remissions and a better tolerability with regard to secondary side-effects . A longer follow-up is needed to assess the long-term effects of initial treatment on disease-free and overall survival and the impact on additional maintenance therapy with interferon alpha |
12,856 | 31,782,063 | They were associated with cytotoxicity , genotoxicity altered inflammatory processes , and reticuloendothelial system toxicity . | Nanotechnology is a vital part of health care system , including the dentistry .
This branch of technology has been incorporated into various fields of dentistry ranging from diagnosis to prevention and treatment .
The latter involves application of numerous bio material s that help in restoration of esthetic and functional dentition .
Over the past decade , these material s were modified through the incorporation of metal nanoparticles ( NP ) like silver ( Ag ) , gold ( Au ) , titanium ( Ti ) , zinc ( Zn ) , copper ( Cu ) , and zirconia ( Zr ) .
They enhanced antimicrobial , mechanical , and regenerative properties of these material s. However , lately , the toxicological implication s of these nanometal particles have been realized .
With this background , the present systematic review is aim ed to gain an insight into the plausible applications and toxic implication s of nano-metal particles as related to dentistry | The purpose of this study was to evaluate the antimicrobial properties of a new formulation containing silver nanoparticles , named Nano Silver Fluoride ( NSF ) , to inhibit Streptococcus mutans biofilm formation on children 's dental enamel . The variations in dental biofilm pH and in the Simplified-Oral-Hygiene-Index ( OHI-S ) also were evaluated after the treatment with NSF . This was a r and omized , double-blind , crossover and prospect i ve pilot clinical trial study in which 12 schoolchildren , aged between 7 - 8 years , had their dental enamel treated with two solutions : S1 - Nano Silver Fluoride and S2 - negative control ( saline solution ) , in different experimental moments . The dental biofilm adhered to enamel treated with NSF had lower values of S. mutans viability ( absorbance ) and colony forming units ( CFU ) than the S0 ( baseline ) and S2 . There was a statistically significant difference between the OHI-S mean values of S0 and S1 . There were no differences between the biofilm pH ( both before and after the use of the test substances ) and among the different groups . These properties suggest that NSF has bactericidal effect against S. mutans biofilm and it may be used for clinical control and prevention of dental biofilm formation In the copper metallurgy workplace air is polluted with condensation aerosols , which a significant fraction of is presented by copper oxide particles < 100 nm . In the scientific literature , there is a lack of their in vivo toxicity characterization and virtually no attempts of enhancing organism ’s resistance to their impact . A stable suspension of copper oxide particles with mean ( ±SD ) diameter 20 ± 10 nm was prepared by laser ablation of pure copper in water . It was being injected intraperitoneally to rats at a dose of 10 mg/kg ( 0.5 mg per mL of deionized water ) three times a week up to 19 injections . In parallel , another group of rats was so injected with the same suspension against the background of oral administration of a “ bio-protective complex ” ( BPC ) comprising pectin , a multivitamin-multimineral preparation , some amino acids and fish oil rich in ω-3 PUFA . After the termination of injections , many functional and biochemical indices for the organism ’s status , as well as pathological changes of liver , spleen , kidneys , and brain microscopic structure were evaluated for signs of toxicity . In the same organs we have measured accumulation of copper while their cells were used for performing the R and om Amplification of Polymorphic DNA ( RAPD ) test for DNA fragmentation . The same features were assessed in control rats infected intraperitoneally with water with or without administration of the BPC . The copper oxide nanoparticles proved adversely bio-active in all respects considered in this study , their active in vivo solubilization in biological fluids playing presumably an important role in both toxicokinetics and toxicodynamics . The BPC proposed and tested by us attenuated systemic and target organs toxicity , as well as genotoxicity of this substance . Judging by experimental data obtained in this investigation , occupational exposures to nano-scale copper oxide particles can present a significant health risk while the further search for its management with the help of innocuous bioprotectors seems to be justified Background The purpose of this in-vitro study was to examine the effect of incorporating different concentrations of Zirconium oxide-Titanium dioxide ( ZrO2-TiO2 ) nanoparticles , which can have antibacterial properties , on the mechanical properties of an orthodontic adhesive . Methods ZrO2-TiO2 ( Zirconium oxide , HWNANO , Hongwu International Group Ltd , China ) -Titanium dioxide , Nanoshell , USA ) nanopowder were incorporated into orthodontic adhesive ( Transbond XT , 3 M Unitek , Monrovia , USA ) with different concentrations ( 0.5 % weight nonofiller and 1 % weight nanofiller ) . The size of nanoparticle was 70–80 nm for ZrO2 and less than 50 nm for TiO2 . For measuring the shear bond strength of the three groups of orthodontic adhesives [ Transbond ( control ) , Transbond mixed with 0.5 % weight ZrO2-TiO2 , and Transbond mixed with 1 % weight ZrO2-TiO2 ] , 30 freshly extracted human first premolars were used and bonded with stainless steel metal brackets ( Dentaurum ® , Discovery ® , Deutschl and ) , using the 3 orthodontic adhesives and 3 M Unitek ; Transbond TM Plus Self-Etching Primer ( 10 sample s in each group ) . The recorded values of compressive strength and tensile strength ( measured separately on 10 sample s of orthodontic adhesives ( add the 3 D size of sample , light cured for 40 s on both sides ) of each orthodontic adhesives ) , as well as the shear bond strength in Mega Pascal unit ( MPa ) were collected and exposed to one-way analysis of variance ( ANOVA ) and Tukey ’s post-hoc tests . Results orthodontic adhesive with 1 % weight ZrO2-TiO2 showed the highest mean compressive ( 73.42 ± 1.55 MPa , p : 0.003 , F : 12.74 ) , tensile strength ( 8.65 ± 0.74 MPa , p : 0.001 , F : 68.20 ) , and shear bond strength ( 20.05 ± 0.2 MPa , p : 0.001 , F : 0.17 ) . Conclusions Adding ZrO2-TiO2 nanoparticle to orthodontic adhesive increased compressive strength , tensile strength , and shear bond strength in vitro , but in vivo studies and r and omized clinical trials are needed to vali date the present findings Objective The potential risk of a nanoparticle as a medical application has raised wide concerns , and this study aims to investigate silver nanoparticle (AgNP)-induced acute toxicities , genotoxicities , target organs and the underlying mechanisms . Methods Sprague-Dawley rats were r and omly divided into 4 groups ( n = 4 each group ) , and AgNP ( containing Ag nanoparticles and released Ag+ , 5 mg/kg ) , Ag+ ( released from the same dose of AgNP , 0.0003 mg/kg ) , 5 % sucrose solution ( vechicle control ) and cyclophophamide ( positive control , 40 mg/kg ) were administrated intravenously for 24 h respectively . Clinical signs and body weight of rats were recorded , and the tissues were subsequently collected for biochemical examination , Ag+ distribution detection , histopathological examination and genotoxicity assays . Results The rank of Ag detected in organs from highest to lowest is lung > spleen > liver > kidney > thymus > heart . Administration of AgNP induced a marked increase of ALT , BUN , TBil and Cre . Histopathological examination results showed that AgNP induced more extensive organ damages in liver , kidneys , thymus , and spleen . Bone marrow micronucleus assay found no statistical significance among groups ( p > 0.05 ) , but the number of aberration cells and multiple aberration cells were predominately increased from rats dosed with Ag+ and AgNP ( p < 0.01 ) , and more polyploidy cells were generated in the AgNP group ( 4.3 % ) compared with control . Conclusion Our results indicated that the AgNP accumulated in the immune system organs , and mild irritation was observed in the thymus and spleen of animals treated with AgNP , but not with Ag+ . The liver and kidneys could be the most affected organs by an acute i.v . dose of AgNP , and significantly increased chromosome breakage and polyploidy cell rates also implied the potential genotoxicity of AgNP . However , particle-specific toxicities and potential carcinogenic effect remain to be further confirmed in a chronic toxicity study Gold nanoparticles have shown great prospect i ve in cancer diagnosis and therapy , but they can not be metabolized and prefer to accumulate in liver and spleen due to their large size . The gold nanoclusters with small size can penetrate kidney tissue and have promise to decrease in vivo toxicity by renal clearance . In this work , we explore the in vivo renal clearance , biodistribution , and toxicity responses of the BSA- and GSH-protected gold nanoclusters for 24 h and 28 days . The BSA-protected gold nanoclusters have low-efficient renal clearance and only 1 % of gold can be cleared , but the GSH-protected gold nanoclusters have high-efficient renal clearance and 36 % of gold can be cleared after 24 h. The biodistribution further reveals that 94 % of gold can be metabolized for the GSH-protected nanoclusters , but only less than 5 % of gold can be metabolized for the BSA-protected nanoclusters after 28 days . Both of the GSH- and BSA-protected gold nanoclusters cause acute infection , inflammation , and kidney function damage after 24 h , but these toxicity responses for the GSH-protected gold nanoclusters can be eliminated after 28 days . Immune system can also be affected by the two kinds of gold nanoclusters , but the immune response for the GSH-protected gold nanoclusters can also be recovered after 28 days . These findings show that the GSH-protected gold nanoclusters have small size and can be metabolized by renal clearance and thus the toxicity can be significantly decreased . The BSA-protected gold nanoclusters , however , can form large compounds and further accumulate in liver and spleen which can cause irreparable toxicity response . Therefore , the GSH-protected gold nanoclusters have great potential for in vivo imaging and therapy , and the BSA-protected gold nanoclusters can be used as the agent of liver cancer therapy Objective . The aim of this study was to evaluate the effect of incorporation of glass fiber , zirconia , and nano-zirconia on the transverse strength of repaired denture base . Material s and Methods . Eighty specimens of heat polymerized acrylic resin were prepared and r and omly divided into eight groups ( n = 10 ) : one intact group ( control ) and seven repaired groups . One group was repaired with autopolymerized resin while the other six groups were repaired using autopolymerized resin reinforced with 2 wt% or 5 wt% glass fiber , zirconia , or nano-zirconia particles . A three-point bending test was used to measure the transverse strength . The results were analyzed using SPSS and repeated measure ANOVA and post hoc least significance ( LSD ) test ( P ≤ 0.05 ) . Results . Among repaired groups it was found that autopolymerized resin reinforced with 2 or 5 wt% nano-zirconia showed the highest transverse strength ( P ≤ 0.05 ) . Repairs with autopolymerized acrylic resin reinforced with 5 wt% zirconia showed the lowest transverse strength value . There was no significant difference between the groups repaired with repair resin without reinforcement , 2 wt% zirconia , and glass fiber reinforced resin . Conclusion . Reinforcing of repair material with nano-zirconia may significantly improve the transverse strength of some fractured denture base polymers Introduction Dental caries is still prevailing worldwide , although different anti caries products have been introduced . Each remineralizing agent has its own shortcomings . Therefore , looking for new agents to have benefits of previous ones with lesser side effects is worthwhile . Aim To determine the remineralization ability of NaF varnish , nano-Hydroxyapatite Serum ( n-HAP ) and Nano Silver Fluoride ( NSF ) on enamel of primary anterior teeth . Material s and Methods Incipient caries were induced in primary sound anterior teeth by storing each specimen in demineralization solution for 72 hours . Then they were r and omly divided into four groups of 15 sample s each : ( 1 ) NaF varnish ; ( 2 ) n-HAP repairing serum ; ( 3 ) NSF and ( 4 ) no treatment ( control ) . Surface Microhardness ( SMH ) was assessed with Vickers micro hardness tester before and after demineralization and after 10 days of pH-cycling . A total of 12 r and om specimens from groups 1 to 4 ( 3 r and om sample s of each group ) were examined by Atomic Force Microscopy ( AFM ) . The SMH values were analysed with one-way and repeated measures ANOVA . Level of significance was set at p=0.05 . Results Post lesion SMH values significantly decreased in all groups ( p<0.001 ) . Post treatment SMH values significantly increased in comparison to post lesion ones ( p<0.001 ) except for control group which was not different statistically ( p=0.86 ) . The highest SMH values were observed in NSF group ( mean 222.90 ± 28.79 ) . Statistically significant differences were shown between all groups ( p<0.05 ) . However , NaF varnish and n-HAP groups were not statistically different ( p=0.165 ) . AFM images demonstrated protective layers in all treated groups . Conclusion The results of this in vitro study suggest that NSF could have the greatest remineralization efficacy . NaF varnish and n-HAP serum were similar in remineralizing initial caries . Future clinical studies are recommended for selection of the most appropriate remineralizing agent in primary teeth Sunscreens , whose main function is to protect the skin against the harmful effects of solar irradiation , should remain at the skin surface or impregnate the first layers of the stratum corneum only and not penetrate into the underlying living tissue . The goal of this work was to assess the penetration of titanium dioxide ( TiO2 ) and methylene bis-benzotriazoyl tetramethylbutylphenol ( MBBT ) , included in a broad-spectrum sunscreen formulation , into human skin in vivo , using the tape stripping method , and in vitro , using a compartmental approach . An additional objective was to propose an easy and minimally invasive approach to determining the percutaneous uptake of sunscreens following topical application . TiO2 and MBBT were quantified using colorimetric assay and HPLC analysis , respectively . The transmission electron microscopy and particle-induced X-ray emission techniques were used to localize the TiO2 in skin sections . More than 90 % of both sunscreens was recovered in the first 15 tape strippings . In addition we have shown that the remaining 10 % did not penetrate the viable tissue , but was localized in the furrows and in the opened infundibulum . Less than 0.1 % of MBBT was detected in the receptor medium , and no TiO2 was detected in the follicle , viable epidermis or dermis . Thus , this in vivo and in vitro penetration study showed an absence of TiO2 penetration into the viable skin layers through either transcorneal or transfollicular pathways and negligible transcutaneous absorption of MBBT . However , differences in distribution within the stratum corneum reinforced the need for a complementary approach , using minimally invasive in vivo methodology and in vitro compartmental analysis .This combination represents a well-adapted method for testing the safety of topically applied sunscreen formulations in real-life conditions AIM Polymethyl-methacrylate ( PMMA ) is commonly used primarily for baseplates of orthodontic appliances ( BOA ) . The activities of cariogenic bacteria in biofilm on these surfaces may contribute to dental caries , gingival inflammation and periodontal disease . The PMMA incorporated with nanoparticles of silver ( NanoAg-I-PMMA ) and NanoAg in situ in PMMA ( NanoAg-IS-PMMA ) have been shown to control the growth of cariogenic bacteria , but clinical trial of anti-cariogenic application of these novel material s in orthodontics has not been evaluated . The main aim of the study is to compare the clinical effectiveness of using NanoAg-IS-PMMA and NanoAg-I-PMMA for construction of new BOA in inhibiting the planktonic growth and biofilm formation of the cariogenic bacteria . MATERIAL S AND METHODS Twenty four patients with a median age of 12.6 years ( 7 - 15 ) harboring Streptococcus mutans , Streptococcus sobrinus and Lactobacillus acidophilus as well as Lactobacillus casei participated in the r and omized , double-blind , cross-over study . The experimental BOA , NanoAg-IS-BOA and NanoAg-I-BOA , contained 0.5 % w/w NanoAg while the control BOA was st and ard PMMA . Antibacterial effect of NanoAg-IS-BOA and NanoAg-I-BOA was assessed against test cariogenic bacteria by planktonic and biofilm bacterial cells growth inhibition . RESULTS The average levels of test cariogenic bacteria in saliva decreased about 2 to 70 fold ( 30.9 - 98.4 % ) compared to baseline depending on the microorganism type and test BOA . Biofilm inhibition analysis demonstrated that NanoAg-I-BOA and NanoAg-IS-BOA inhibited the biofilm of all test bacteria by 20.1 to 79.9 % compared to BOA . NanoAg-IS-BOA had a strong anti-biofilm effect against S. mutans , S. sobrinus and L. casei . However , NanoAg-I-BOA showed only slight anti-biofilm effects on test bacteria . Most notably , at all period of the clinical trial , NanoAg-IS-BOA showed a higher antibacterial activity than NanoAg-I-BOA . CONCLUSION Based on the novel data that presented here , the NanoAg-IS-BOA had strong antimicrobial activity in the planktonic phase and subsequent biofilm formation of the cariogenic bacteria . CLINICAL SIGNIFICANCE Wearing of NanoAg-IS-BOA has the potential to minimize dental plaque formation and caries during orthodontic treatment OBJECTIVES The aim of the present study was to investigate antibacterial characteristic and Enterococcus faecalis ( E. faecalis ) biofilm suppression effect of different vehicles of calcium hydroxide as intracanal medicaments in short and long-term . METHODS Fifty-four human single-root teeth were contaminated with E. faecalis bacteria . The teeth were r and omly divided into three experimental ( n=16 ) and one control group ( n=6 ) . Each group was then exposed to various intracanal medicaments , namely calcium hydroxide paste ( group 1 ) , calcium hydroxide with chlorhexidine ( group 2 ) , calcium hydroxide with silver nanoparticles suspension ( AgNPs ) ( group 3 ) , and saline as the control group ( group 4 ) . Cultures were made from each group after one week and one month , and the number of colonies was counted . Moreover , a sample of each group was examined under electron microscope . Kruskal-Wallis test served for inter-group comparisons , and Mann-Whitney test served for comparison between the two incubation periods . RESULTS All the intracanal medicaments result ed in significant decrease in number of colonies compared to control group in both incubation periods . After one week , the mixture of calcium hydroxide and AgNPs was the most effective medicament against E. faecalis bacteria ( p<.05 ) . No significant difference in antibacterial effect of the medicaments existed after one month incubation period ( p>.05 ) . CONCLUSION AgNPs was more effective on the E. faecalis biofilm than other tested vehicles in short-term medication . CLINICAL SIGNIFICANCE AgNPs seems to have a good potential to be used as an appropriate vehicle of calcium hydroxide in order to eliminate of E. faecalis biofilm from human dentine in short-term Background To evaluate the clinical cariostatic efficacy of a concocted 5 % Nano-silver incorporated Sodium fluoride ( NSSF ) dental varnish with 38 % Silver diamine fluoride ( SDF ) in preventing the progression of dentinal caries of primary molars . Material and Methods A total of 159 active dentinal carious lesions in primary molars ( from 50 children ) were selected and r and omly divided into two groups ; NSSF and SDF . Varnish application was performed at the baseline visit and follow-up is carried out at 1 , 3 , 6 and 12 months . Parameters such as caries activity , depth , size , colour , and presence or absence of pain were noted at baseline and follow-up visits . Results The intergroup comparison of caries activity status did not reveal significant difference between the number of active and arrested caries lesions in NSSF and SDF groups at any visit ( p > 0.05 ) during the 12-month follow-up . There was no difference between overall failure and success rates between the two groups at any follow-up period ( p-0.48 ) . Conclusions Annual application of 5 % NSSF is better than or equal to 38 % SDF in preventing the progression of dentinal caries of primary molars . NSSF does not cause dark staining of dentinal tissue compared to the SDF and the use of NSSF can be recommended in children . Key words : Children , Nano-silver fluoride , Primary teeth , Silver diamine fluoride BACKGROUND Untreated dental caries in children remains a public health challenge in poor communities . OBJECTIVES This prospect i ve controlled clinical trial investigated the effectiveness of a new anti-caries agent , Nano Silver Fluoride ( NSF ) , applied once a year to arrest caries in children . METHODS One hundred thirty decayed primary teeth were r and omly divided into two groups : NSF as the experimental agent and water as the control group . Teeth were clinical ly diagnosed and treated by one masked examiner and followed up at seven days and five and 12 months by another calibrated examiner who was blinded to the type of treatment . The criteria of the ICDAS II were followed to determine the activity of lesion and the diagnosis of caries . The Pearson 's chi-square test was used to compare the groups during different follow-up exams . RESULTS At seven days , 81 % of teeth in the NSF group exhibited arrested caries , whereas in controls , no teeth had arrested decay ( p<0.001 ) [ PF , prevented fraction=81 % ] . After five months , the NSF group had 72.7 % with arrested decay , and the control group had 27.4 % ( p<0.001 ) [ PF=62.5 % ] . At 12 months , 66.7 % of the lesions treated with NSF were still arrested , while the control group had 34.7 % remaining arrested ( p=0.003 ) [ PF=50 % ] . The number need to treat ( NNT ) at five months was two , and at 12 months , the number was three . CLINICAL SIGNIFICANCE The NSF formulation is effective to arrest active dentine caries and not stain teeth . CONCLUSIONS NSF was demonstrated to be effective in arresting caries in children in poor communities |
12,857 | 32,121,180 | Most self-management interventions did not measure health literacy or patient activation as an outcome .
Successful interventions were multicomponent and comprehensive in addressing self-management .
There is a need to evaluate the impact of comprehensive self-management interventions that address and measure both health literacy and patient activation on health outcomes for COPD patients | Self-management ( SM ) includes activities that patients initiate and perform in the interest of controlling their disease and maintaining good health and well-being .
This review examines the health literacy and patient activation elements of self-management interventions for Chronic Obstructive Pulmonary Diseases ( COPD ) patients .
We investigated the effects of the intervention on health-related quality of life , self-efficacy , depression , and anxiety among people with COPD . | BACKGROUND Better self management could improve quality of life ( QoL ) and reduce hospital admissions in chronic obstructive pulmonary disease ( COPD ) , but the best way to promote it remains unclear . AIM To explore the feasibility , effectiveness and cost effectiveness of a novel , layperson-led , theoretically driven COPD self-management support programme . DESIGN AND SETTING Pilot r and omised controlled trial in one UK primary care trust area . METHOD Patients with moderate to severe COPD were identified through primary care and r and omised 2:1 to the 7-week-long , group intervention or usual care . Outcomes at baseline , 2 , and 6 months included self-reported health , St George 's Respiratory Question naire ( SGRQ ) , EuroQol , and exercise . RESULTS Forty-four per cent responded to GP invitation , 116 were r and omised : mean ( st and ard deviation [ SD ] ) age 69.5 ( 9.8 ) years , 46 % male , 78 % had unscheduled COPD care in the previous year . Forty per cent of intervention patients completed the course ; 35 % attended no sessions ; and 78 % participants completed the 6-month follow-up question naire . Results suggest that the intervention may increase both QoL ( mean EQ-5D change 0.12 ( 95 % confidence interval [ CI ] = -0.02 to 0.26 ) higher , intervention versus control ) and exercise levels , but not SGRQ score . Economic analyses suggested that with thresholds of £ 20 000 per quality -adjusted life-year gained , the intervention is likely to be cost-effective . CONCLUSION This intervention has good potential to meet the UK National Institute for Health and Clinical Excellence criteria for cost effectiveness , and further research is warranted . However , to make a substantial impact on COPD self-management , it will also be necessary to explore other ways to enable patients to access self-management education The new COPD -GRIP ( Chronic Obstructive Pulmonary Disease – Guidance , Research on Illness Perception ) intervention translates evidence regarding illness perceptions and health-related quality of life ( HRQoL ) into a nurse intervention to guide COPD patients and to improve health outcomes . It describes how to assess and discuss illness perceptions in a structured way . This study aim ed to assess the effectiveness of the intervention in primary care . A cluster r and omised controlled trial was conducted within 30 general practice s and five home-care centres , including 204 COPD patients . 103 patients were r and omly assigned to the intervention group and 101 patients to the usual-care group . To assess differences , repeated multilevel linear mixed modelling analyses were used . Primary outcome was change in health status on the Clinical COPD Question naire ( CCQ ) at 9 months . Secondary outcomes were HRQoL , daily activities , health education impact and changes in illness perceptions . There was no significant difference between the groups in the CCQ at 9 months . We found a significant increase in health-directed behaviour at 6 weeks ( p=0.024 ) and in personal control ( p=0.005 ) at 9 months in favour of the intervention group . The COPD -GRIP intervention , practised by nurses , did not improve health status in COPD patients in primary care . However , the intervention has benefits in improving the ability to control the disease and health-related behaviours in the short term . Therefore , taking illness perceptions into account when stimulating healthy behaviours in COPD patients should be considered . Further study on influencing the health status and HRQoL is needed . COPD illness perception intervention improved health behaviours in the short term , but did not improve health status Objectives Pulmonary rehabilitation ( PR ) provides benefit for patients with chronic obstructive pulmonary disease ( COPD ) in terms of quality of life ( QoL ) and exercise capacity ; however , the effects diminish over time . Our aim was to evaluate a maintenance programme for patients who had completed PR . Setting Primary and secondary care PR programmes in Norfolk . Participants 148 patients with COPD who had completed at least 60 % of a st and ard PR programme were r and omised and data are available for 110 patients . Patients had greater than 20 pack year smoking history and less than 80 % predicted forced expiratory volume in 1 s but no other significant disease or recent respiratory tract infection . Interventions Patients were r and omised to receive a maintenance programme or st and ard care . The maintenance programme consisted of 2 h ( 1 h individually tailored exercise training and 1 h education programme ) every 3 months for 1 year . Primary and secondary outcome measures The Chronic Respiratory Question naire ( CRQ ) ( primary outcome ) , endurance shuttle walk test ( ESWT ) , EuroQol ( EQ5D ) , hospital anxiety and depression score ( HADS ) , body mass index ( BMI ) , body fat , activity levels ( overall score and activity diary ) and exacerbations were assessed before and after 12 months . Results There was no statistically significant difference between the groups for the change in CRQ dyspnoea score ( primary end point ) at 12 months which amounted to 0.19 ( −0.26 to 0.64 ) units or other domains of the CRQ . There was no difference in the ESWT duration ( −10.06 ( −191.16 to 171.03 ) seconds ) , BMI , body fat , EQ5D , MET-minutes , activity rating , HADS , exacerbations or admissions . Conclusions A maintenance programme of three monthly 2 h sessions does not improve outcomes in patients with COPD after 12 months . We do not recommend that our maintenance programme is adopted . Other methods of sustaining the benefits of PR are required . Trial registration number NCT00925171 The pivotal objective of chronic obstructive pulmonary disease ( COPD ) self-management programmes is behaviour change to avoid moderate and severe exacerbations and improve health related quality of life . In a prospect ively planned , controlled study , COPD patients who participated in the “ Living well with COPD ” ( LWW COPD ) self-management intervention were compared with usual care patients from the primary care COPD Cohort ICE COLD ERIC , who did not receive self-management intervention ( NCT00706602 ) The primary outcome was behaviour change and disease-specific health related quality of life after 1 year . Secondary end-points included exacerbation rates . We calculated mixed linear , zero-inflated negative binomial and logistic regression models and used propensity scores to counteract confounding . 467 patients , 71 from the LWW COPD and 396 from the usual care cohort , were included . The differences between intervention and control were 0.54 ( 95 % CI 0.13−0.94 ) on the Chronic Respiratory Question naire domain “ mastery ” , 0.55 ( 95 % CI 0.11−0.99 ) on “ fatigue ” , 0.54 ( 0.14−0.93 ) on “ emotional function ” and 0.64 ( 95 % CI 0.14−1.14 ) on “ dyspnoea ” . The intervention considerably reduced the risk of moderate and severe exacerbations ( incidence rate ratio 0.36 , 95 % CI 0.25−0.52 ) . Self-management coaching in primary care improves health-related quality of life and lowers exacerbation rates and health care use . COPD self-management coaching improves health-status and lowers exacerbation rates among patients in primary care Background Frequent users of healthcare services are a vulnerable population that deserves attention due to high costs and negative outcomes such as lower quality of life and higher mortality . Healthcare systems should offer interventions tailored to their needs and to their level of health literacy , including strategies to promote activation . The relationship between health literacy and patient activation remains to be explored . The aim of this study was to examine the association between health literacy and patient activation in a population of frequent users of healthcare services with chronic diseases . Methods Cross-sectional data were collected ( before r and omization ) through a clinical trial evaluating a case management intervention in primary care . Participants ( n = 247 ) were recruited from the list of frequent users of 4 Family Medicine Groups ( FMG ) in the Saguenay-Lac-St-Jean region of Québec ( Canada ) . They completed question naires by self-report during an encounter with a research assistant : ( 1 ) the Newest Vital Sign ( NVS ) to evaluate health literacy ( independent variable ) ; and ( 2 ) the Patient Activation Measure-13 ( PAM-13 ) to evaluate patient activation ( dependent variable ) . The relationship between health literacy and activation was examined using biserial correlations . Results No association was found between health literacy ( independent variable ) and patient activation ( rb = 0.075 , ρ = 0.07 ) for this population of frequent users of healthcare services . Conclusions This study suggests that there is no relationship between health literacy and patient activation among frequent users of healthcare services . Trial registration NCT01719991 . Registered October 25 , 2012 Background Self-management education programs ( SMEPs ) are potentially effective in the symptomatic management of COPD . Little is presently known about the effectiveness of these programs in Chinese COPD patients . The objective of this study was to evaluate the effectiveness of a specifically design ed SMEP on levels of self-efficacy in Chinese patients with COPD . Material s and methods Based on the Medical Research Council framework for evaluating complex interventions , an exploratory phase r and omized controlled trial was employed to examine the effects of an SMEP . Self-efficacy was the primary outcome using the COPD Self-efficacy Scale , measured at baseline and 6 months after the program . Qualitative data were sequentially collected from these patients via three focus groups to supplement the quantitative findings . Results The experimental group displayed significant improvement in their general self-efficacy ( Z = −2.44 , P=0.015 ) and specifically in confronting 1 ) physical exertion ( Z = −2.57 , P=0.01 ) , 2 ) weather/environment effects ( Z = −2.63 , P<0.001 ) and 3 ) intense emotions ( Z = −2.54 , P=0.01 ) . Three themes emerged from the focus groups : greater disease control , improved psychosocial well-being and perceived incapability and individuality . The connection of the quantitative and qualitative data demonstrated that individual perceptual constancy of patients could be a determining factor modulating the effectiveness of this type of intervention . Conclusion These findings highlight the potential putative benefits of an SMEP in Chinese patients with COPD . Further attention should be given to cultural considerations when developing this type of intervention in Chinese population s with COPD and other chronic diseases Background Patient education is a key component in the management of chronic obstructive pulmonary disease ( COPD ) . Delivering effective education to ethnic groups with COPD is a challenge . The objective of this study was to develop and assess the effectiveness of culturally and linguistically specific audiovisual educational material s in supporting self-management practice s in M and arin- and Cantonese-speaking patients . Methods Educational material s were developed using participatory approach ( patients involved in the development and pilot test of educational material s ) , followed by a r and omized controlled trial that assigned 91 patients to three intervention groups with audiovisual educational interventions and one control group ( pamphlet ) . The patients were recruited from outpatient clinics . The primary outcomes were improved inhaler technique and perceived self-efficacy to manage COPD . The secondary outcome was improved patient underst and ing of pulmonary rehabilitation procedures . Results Subjects in all three intervention groups , compared with control subjects , demonstrated postintervention improvements in inhaler technique ( P<0.001 ) , preparedness to manage a COPD exacerbation ( P<0.01 ) , ability to achieve goals in managing COPD ( P<0.01 ) , and underst and ing pulmonary rehabilitation procedures ( P<0.05 ) . Conclusion Culturally appropriate educational interventions design ed specifically to meet the needs of M and arin and Cantonese COPD patients are associated with significantly better underst and ing of self-management practice s. Self-management education led to improved proper use of medications , ability to manage COPD exacerbations , and ability to achieve goals in managing COPD . Clinical implication A relatively simple culturally appropriate disease management education intervention improved inhaler techniques and self-management practice s. Further research is needed to assess the effectiveness of self-management education on behavioral change and patient empowerment strategies BACKGROUND New care modes in primary care may affect patients ' experienced continuity of care . AIM To analyse whether experienced continuity for patients with chronic obstructive pulmonary disease ( COPD ) changes after different care modes are introduced , and to analyse the relationship between continuity of care and patients ' quality of life . DESIGN AND SETTING R and omised controlled trial with 2-year follow-up in general practice in the Netherl and s. METHOD A total of 180 patients with COPD were r and omly assigned to three different care modes : self-management , regular monitoring by a practice nurse , and care provided by the GP at the patient 's own initiative ( usual care ) . Experienced continuity of care as personal continuity ( proportion of visits with patient 's own GP ) and team continuity ( continuity by the primary healthcare team ) was measured using a self-administered patient question naire . Quality of life was measured using the Chronic Respiratory Question naire . RESULTS Of the final sample ( n = 148 ) , those patients receiving usual care experienced the highest personal continuity , although the chance of not contacting any care provider was also highest in this group ( 29 % versus 2 % receiving self-management , and 5 % receiving regular monitoring ) . There were no differences in experienced team continuity in the three care modes . No relationship was found between continuity and changes in quality of life . CONCLUSION Although personal continuity decreases when new care modes are introduced , no evidence that this affects patients ' experienced team continuity or patients ' quality of life was found . Patients still experienced smooth , ongoing care , and considered care to be connected . Overall , no evidence was found indicating that the introduction of new care modes in primary care for patients with COPD should be discouraged Objective To determine whether supported self management in chronic obstructive pulmonary disease ( COPD ) can reduce hospital readmissions in the United Kingdom . Design R and omised controlled trial . Setting Community based intervention in the west of Scotl and . Participants Patients admitted to hospital with acute exacerbation of COPD . Intervention Participants in the intervention group were trained to detect and treat exacerbations promptly , with ongoing support for 12 months . Main outcome measures The primary outcome was hospital readmissions and deaths due to COPD assessed by record linkage of Scottish Morbidity Records ; health related quality of life measures were secondary outcomes . Results 464 patients were r and omised , stratified by age , sex , per cent predicted forced expiratory volume in 1 second , recent pulmonary rehabilitation attendance , smoking status , deprivation category of area of residence , and previous COPD admissions . No difference was found in COPD admissions or death ( 111/232 ( 48 % ) v 108/232 ( 47 % ) ; hazard ratio 1.05 , 95 % confidence interval 0.80 to 1.38 ) . Return of health related quality of life question naires was poor ( n=265 ; 57 % ) , so that no useful conclusions could be made from these data . Pre-planned subgroup analysis showed no differential benefit in the primary outcome relating to disease severity or demographic variables . In an exploratory analysis , 42 % ( 75/150 ) of patients in the intervention group were classified as successful self managers at study exit , from review of appropriateness of use of self management therapy . Predictors of successful self management on stepwise regression were younger age ( P=0.012 ) and living with others ( P=0.010 ) . COPD readmissions/deaths were reduced in successful self managers compared with unsuccessful self managers ( 20/75 ( 27 % ) v 51/105 ( 49 % ) ; hazard ratio 0.44 , 0.25 to 0.76 ; P=0.003 ) . Conclusion Supported self management had no effect on time to first readmission or death with COPD . Exploratory subgroup analysis identified a minority of participants who learnt to self manage ; this group had a significantly reduced risk of COPD readmission , were younger , and were more likely to be living with others . Trial registration Clinical trials NCT 00706303 Objective To assess the long term effects of two different modes of disease management ( comprehensive self management and routine monitoring ) on quality of life ( primary objective ) , frequency and patients ’ management of exacerbations , and self efficacy ( secondary objectives ) in patients with chronic obstructive pulmonary disease ( COPD ) in general practice . Design 24 month , multicentre , investigator blinded , three arm , pragmatic , r and omised controlled trial . Setting 15 general practice s in the eastern part of the Netherl and s. Participants Patients with COPD confirmed by spirometry and treated in general practice . Patients with very severe COPD or treated by a respiratory physician were excluded . Interventions A comprehensive self management programme as an adjunct to usual care , consisting of four tailored sessions with ongoing telephone support by a practice nurse ; routine monitoring as an adjunct to usual care , consisting of 2 - 4 structured consultations a year with a practice nurse ; or usual care alone ( contacts with the general practitioner at the patients ’ own initiative ) . Outcome measures The primary outcome was the change in COPD specific quality of life at 24 months as measured with the chronic respiratory question naire total score . Secondary outcomes were chronic respiratory question naire domain scores , frequency and patients ’ management of exacerbations measured with the Nijmegen telephonic exacerbation assessment system , and self efficacy measured with the COPD self-efficacy scale . Results 165 patients were allocated to self management ( n=55 ) , routine monitoring ( n=55 ) , or usual care alone ( n=55 ) . At 24 months , adjusted treatment differences between the three groups in mean chronic respiratory question naire total score were not significant . Secondary outcomes did not differ , except for exacerbation management . Compared with usual care , more exacerbations in the self management group were managed with bronchodilators ( odds ratio 2.81 , 95 % confidence interval 1.16 to 6.82 ) and with prednisolone , antibiotics , or both ( 3.98 , 1.10 to 15.58 ) . Conclusions Comprehensive self management or routine monitoring did not show long term benefits in terms of quality of life or self efficacy over usual care alone in COPD patients in general practice . Patients in the self management group seemed to be more capable of appropriately managing exacerbations than did those in the usual care group . Trial registration Clinical trials NCT00128765 AIMS AND OBJECTIVES To test the effect of a Health Belief Model-based nursing intervention on healthcare outcomes in Chinese patients with moderate to severe COPD . BACKGROUND The Health Belief Model ( HBM ) has been internationally vali date d in a variety of chronic conditions . However , nursing intervention based on the HBM is less explored in Chinese patients with COPD . DESIGN A r and omised controlled trial . METHODS Enrolled patients were r and omly assigned to the intervention and control groups . Patients in the intervention group received a 20- to 30-minute HBM-based nursing intervention every 2 days during the hospitalisation period after disease conditions were stable , with additional follow-ups after discharge . Patients in the control group received routine nursing care . RESULTS Patients had significantly increased scores of health belief and self-efficacy after receiving the HBM-based nursing intervention . After receiving the 3-month follow-up , patients in the intervention group had significantly higher mean total scores in the Health Belief Scale and the COPD Self-Efficacy Scale , as well as in all the subscales , than those in the control group except the perceived disease seriousness . Results showed that the value of FEV1 /FVC ratio had a significant difference between study groups before and after the intervention . Results also indicated that mean scores of the Dyspnea Scale , 6-minute walking distance and ADL were significantly different between the groups and between the study time-points . CONCLUSIONS Among patients with moderate to severe COPD , nursing intervention based on the HBM can enhance their health belief and self-efficacy towards the disease management , decrease dyspnoea and improve exercise tolerance and ADL . RELEVANCE TO CLINICAL PRACTICE Nurses can use the HBM-based intervention to enhance patients ' health belief and self-efficacy towards the management of COPD , and subsequently benefit healthcare outcomes Background Limited evidence exists regarding the relationship between health literacy and health-related quality of life ( HRQoL ) in Australian patients from primary care . The objective of this study was to investigate the impact of health literacy on HRQoL in a large sample of patients without known vascular disease or diabetes and to examine whether the difference in HRQoL between low and high health literacy groups was clinical ly significant . Methods This was a cross-sectional study of baseline data from a cluster r and omised trial . The study included 739 patients from 30 general practice s across four Australian states conducted in 2012 and 2013 using the st and ard Short Form Health Survey ( SF-12 ) version 2 . SF-12 physical component score ( PCS-12 ) and mental component score ( MCS-12 ) are derived using the st and ard US algorithm . Health literacy was measured using the Health Literacy Management Scale ( HeLMS ) . Multilevel regression analysis ( patients at level 1 and general practice s at level 2 ) was applied to relate PCS-12 and MCS-12 to patient reported life style risk behaviours including health literacy and demographic factors . Results Low health literacy patients were more likely to be smokers ( 12 % vs 6 % , P = 0.005 ) , do insufficient physical activity ( 63 % vs 47 % , P < 0.001 ) , be overweight ( 68 % vs 52 % , P < 0.001 ) , and have lower physical health and lower mental health with large clinical ly significant effect sizes of 0.56 ( B ( regression coefficient ) = −5.4 , P < 0.001 ) and 0.78(B = -6.4 , P < 0.001 ) respectively after adjustment for confounding factors . Patients with insufficient physical activity were likely to have a lower physical health score ( effect size = 0.42 , B = −3.1 , P < 0.001 ) and lower mental health ( effect size = 0.37 , B = −2.6 , P < 0.001 ) . Being overweight tended to be related to a lower PCS-12 ( effect size = 0.41 , B = −1.8 , P < 0.05 ) . Less well-educated , unemployed and smoking patients with low health literacy reported worse physical health . Health literacy accounted for 45 and 70 % of the total between patient variance explained in PCS-12 and MCS-12 respectively . Conclusions Addressing health literacy related barriers to preventive care may help reduce some of the disparities in HRQoL. Recognising and tailoring health related communication to those with low health literacy may improve health outcomes including HRQoL in general practice Background : Chronic obstructive pulmonary disease ( COPD ) generates a high burden on health care , and hospital admissions represent a substantial proportion of the overall costs of the disease . Integrated care ( IC ) has shown efficacy to reduce hospitalisations in COPD patients at a pilot level . Deployment strategies for IC services require assessment of effectiveness at the health care system level . Aims : The aim of this study was to explore the effectiveness of a community-based IC service in preventing hospitalisations and emergency department ( ED ) visits in stable frail COPD patients . Methods : From April to December 2005 , 155 frail community-dwelling COPD patients were r and omly allocated either to IC ( n=76 , age 73 ( 8) years , forced expiratory volume during the first second , FEV1 41(19 ) % predicted ) or usual care ( n=84 , age 75(9 ) years , FEV1 44 ( 20 ) % predicted ) and followed up for 12 months . The IC intervention consisted of the following : ( a ) patient ’s empowerment for self-management ; ( b ) an individualised care plan ; ( c ) access to a call centre ; and ( d ) coordination between the levels of care . Thereafter , hospital admissions , ED visits and mortality were monitored for 6 years . Results : IC enhanced self-management ( P=0.02 ) , reduced anxiety – depression ( P=0.001 ) and improved health-related quality of life ( P=0.02 ) . IC reduced both ED visits ( P=0.02 ) and mortality ( P=0.03 ) but not hospital admission . No differences between the two groups were seen after 6 years . Conclusion : The intervention improved clinical outcomes including survival and decreased the ED visits , but it did not reduce hospital admissions . The study facilitated the identification of two key requirements for adoption of IC services in the community : appropriate risk stratification of patients , and preparation of the community-based work force Objective To evaluate the effectiveness of a structured education pulmonary rehabilitation programme on the health status of people with chronic obstructive pulmonary disease ( COPD ) . Design Two-arm , cluster r and omised controlled trial . Setting 32 general practice s in the Republic of Irel and . Participants 350 participants with a diagnosis of moderate or severe COPD . Intervention Experimental group received a structured education pulmonary rehabilitation programme , delivered by the practice nurse and physiotherapist . Control group received usual care . Main outcome measure Health status as measured by the Chronic Respiratory Question naire ( CRQ ) at baseline and at 12–14 weeks postcompletion of the programme . Results Participants allocated to the intervention group had statistically significant higher mean change total CRQ scores ( adjusted mean difference ( MD ) 1.11 , 95 % CI 0.35 to 1.87 ) . However , the CI does not exclude a smaller difference than the one that was prespecified as clinical ly important . Participants allocated to the intervention group also had statistically significant higher mean CRQ Dyspnoea scores after intervention ( adjusted MD 0.49 , 95 % CI 0.20 to 0.78 ) and CRQ Physical scores ( adjusted MD 0.37 , 95 % CI 0.14 to 0.60 ) . However , CIs for both the CRQ Dyspnoea and CRQ Physical subscales do not exclude smaller differences as prespecified as clinical ly important . No other statistically significant differences between groups were seen . Conclusions A primary care based structured education pulmonary rehabilitation programme is feasible and may increase local accessibility to people with moderate and severe COPD . Trial registration IS RCT N52403063 Studies of programmes of self-management support for chronic obstructive pulmonary disease ( COPD ) have been inconclusive . The Self-Management Programme of Activity , Coping and Education ( SPACE ) FOR COPD is a 6-week self-management intervention for COPD , and this study aim ed to evaluate the effectiveness of this intervention in primary care . A single-blind r and omised controlled trial recruited people with COPD from primary care and r and omised participants to receive usual care or SPACE FOR COPD . Outcome measures were performed at baseline , 6 weeks and 6 months . The primary outcome was symptom burden , measured by the self-reported Chronic Respiratory Question naire ( CRQ-SR ) dyspnoea domain . Secondary outcomes included other domains of the CRQ-SR , shuttle walking tests , disease knowledge , anxiety , depression , self-efficacy , smoking status and healthcare utilisation . 184 people with COPD were recruited and r and omised . At 6 weeks , there were significant differences between groups in CRQ-SR dyspnoea , fatigue and emotion scores , exercise performance , anxiety , and disease knowledge . At 6 months , there was no between-group difference in change in CRQ-SR dyspnoea . Exercise performance , anxiety and smoking status were significantly different between groups at 6 months , in favour of the intervention . This brief self-management intervention did not improve dyspnoea over and above usual care at 6 months ; however , there were gains in anxiety , exercise performance , and disease knowledge . A brief self-management programme for COPD improves some patient outcomes ; however , more support may be required Little is known about effects of community-based physiotherapeutic exercise programmes incorporated in COPD self-management programmes . In a r and omised trial , the effect of such a programme ( COPE-active ) on exercise capacity and various secondary outcomes including daily activity as a marker of behaviour change was evaluated . All patients attended four 2-h self-management sessions . In addition the intervention group participated in the COPE-active programme offered by physiotherapists of private practice s , consisting of a 6-month " compulsory " period ( 3 sessions/week ) and subsequently a 5-month " optional " period ( 2 sessions/week ) . Because COPE-active was intended to change behaviour with regard to exercise , one session/week in both periods consisted of unsupervised home-based exercise training . Of 153 patients , 74 intervention and 68 control patients completed the one-year follow-up . Statistically significant between-group differences in incremental shuttle walk test-distance ( 35.1 m ; 95 % CI ( 8.4 ; 61.8 ) ) and daily activity ( 1190 steps/day ; 95 % CI ( 256 ; 2125 ) ) were found in favour of the intervention group . Over the 12-month period a significant difference of the chronic respiratory question naire ( CRQ ) dyspnoea-score ( 0.33 points ; 95 % CI ( 0.01 ; 0.64 ) ) and a non-significant difference of the endurance shuttle walk test ( 135 m ( 95 % CI ( -29 ; 298 ) ) was found . No differences were found in the other CRQ-components , anxiety and depression scores and percentage of fat free mass . This study demonstrates that a community-based reactivation programme improves exercise capacity in patients with moderately to severe COPD . Even more important , the programme improves actual daily activity after one-year which indicates behaviour change with regard to daily exercise . Registered trail number : IS RCT N81447311 BACKGROUND AND OBJECTIVE Long-term effectiveness of action plans in patients with chronic obstructive pulmonary disease ( COPD ) is minimally investigated . We have evaluated the (cost-)effectiveness of a self-management programme with or without self-treatment of exacerbations after 2 years follow-up . METHODS Self-management with or without self-treatment of exacerbations was r and omly assigned to patients . All patients participated in four self-management meetings . Patients in the self-treatment group ( STG ) also learned to use an action plan to start a course of prednisolone and /or antibiotics in case of worsening of symptoms . Primary outcome was the duration and severity of exacerbations . RESULTS Data of 70 COPD patients in the STG and 72 patients in the control group ( CG ) were analysed . Over 2 years , the median number of exacerbation days was significantly lower in the STG ( 50 , IQR : 32 - 115 ) compared with the CG ( 82 , IQR : 22 - 186 ) ( P = 0.047 ) , as was the mean symptom score of an exacerbation ( STG : 43.4 , IQR 27.2 - 68.6 vs CG : 55.9 , IQR : 31.2 - 96.8 ) ( P = 0.029 ) . Also , patients in the STG visited the respiratory physician and emergency department less frequently than patients in the CG with incidence rate ratios of 1.52 ( 95 % CI : 1.28 - 1.79 ) and 2.27 ( 95 % CI : 1.11 - 4.62 ) , respectively . Direct medical costs per patient over 2 years were € 1078 lower in the STG . CONCLUSION Self-treatment of exacerbations is beneficial in COPD patients without significant comorbidities because it reduces exacerbation duration , exacerbation severity and health-care utilization leading to considerable cost savings Background : Inhaled medications are recommended as first-line treatment for chronic obstructive pulmonary disease ( COPD ) and can reduce exacerbations and hospitalizations . Low health literacy is associated with poor inhaler technique . Objective : This study examined whether h and outs written specifically for patients with low health literacy are more effective in showing patients how to use their medications when compared to st and ard education material s. Methods : A prospect i ve , experimental study was performed at a community-based hospital . Patients included in the study were admitted to the hospital with a diagnosis of COPD , taking at least 1 inhaled medication and identified as having low health literacy based on a Rapid Estimate of Adult Literacy in Medicine — Short Form . Low health literacy h and outs were compared against the st and ard hospital educational material s for inhalers . Correct technique during each demonstration was evaluated using a st and ardized checklist . Results : Mean baseline scores for inhaler technique were 12.2 ± 2.2 steps correct for the control group and 13.4 ± 1.3 for the low health-literacy group of the 18 maximum points ( P = nonsignificant ) . The mean change in inhaler technique score for the control group was 1.0 ± 1.8 , while the mean change in inhaler technique score for the low health-literacy group was 2.1 ± 2.7 ( P = .03 ) RATIONALE Hospital readmission for chronic obstructive pulmonary disease ( COPD ) has attracted attention owing to the burden to patients and the health care system . There is a knowledge gap on approaches to reducing COPD readmissions . OBJECTIVES To determine the effect of comprehensive health coaching on the rate of COPD readmissions . METHODS A total of 215 patients hospitalized for a COPD exacerbation were r and omized at hospital discharge to receive either ( 1 ) motivational interviewing-based health coaching plus a written action plan for exacerbations ( the use of antibiotics and oral steroids ) and brief exercise advice or ( 2 ) usual care . MEASUREMENTS AND MAIN RESULTS We evaluated the rate of COPD -related hospitalizations during 1 year of follow-up . The absolute risk reductions of COPD -related rehospitalization in the health coaching group were 7.5 % ( P = 0.01 ) , 11.0 % ( P = 0.02 ) , 11.6 % ( P = 0.03 ) , 11.4 % ( P = 0.05 ) , and 5.4 % ( P = 0.24 ) at 1 , 3 , 6 , 9 , and 12 months , respectively , compared with the control group . The odds ratios for COPD hospitalization in the intervention arm compared with the control arm were 0.09 ( 95 % confidence interval [ CI ] , 0.01 - 0.77 ) at 1 month postdischarge , 0.37 ( 95 % CI , 0.15 - 0.91 ) at 3 months postdischarge , 0.43 ( 95 % CI , 0.20 - 0.94 ) at 6 months postdischarge , and 0.60 ( 95 % CI , 0.30 - 1.20 ) at 1 year postdischarge . The missing value rate for the primary outcome was 0.4 % ( one patient ) . Disease-specific quality of life improved significantly in the health coaching group compared with the control group at 6 and 12 months , based on the Chronic Respiratory Disease Question naire emotional score ( emotion and mastery domains ) and physical score ( dyspnea and fatigue domains ) ( P < 0.05 ) . There were no differences between groups in measured physical activity at any time point . CONCLUSIONS Health coaching may represent a feasible and possibly effective intervention design ed to reduce COPD readmissions . Clinical trial registered with www . clinical trials.gov ( NCT01058486 ) OBJECTIVE The Patient Activation Measure ( PAM ) is a 22-item measure that assesses patient knowledge , skill , and confidence for self-management . The measure was developed using Rasch analyses and is an interval level , unidimensional , Guttman-like measure . The current analysis is aim ed at reducing the number of items in the measure while maintaining adequate precision . STUDY METHODS We relied on an iterative use of Rasch analysis to identify items that could be eliminated without loss of significant precision and reliability . With each item deletion , the item scale locations were recalibrated and the person reliability evaluated to check if and how much of a decline in precision of measurement result ed from the deletion of the item . DATA SOURCES The data used in the analysis were the same data used in the development of the original 22-item measure . These data were collected in 2003 via a telephone survey of 1,515 r and omly selected adults . Principal Findings . The analysis yielded a 13-item measure that has psychometric properties similar to the original 22-item version . The scores for the 13-item measure range in value from 38.6 to 53.0 ( on a theoretical 0 - 100 point scale ) . The range of values is essentially unchanged from the original 22-item version . Subgroup analysis suggests that there is a slight loss of precision with some subgroups . CONCLUSIONS The results of the analysis indicate that the shortened 13-item version is both reliable and valid Objective To investigate the long term effectiveness of integrated disease management delivered in primary care on quality of life in patients with chronic obstructive pulmonary disease ( COPD ) compared with usual care . Design 24 month , multicentre , pragmatic cluster r and omised controlled trial Setting 40 general practice s in the western part of the Netherl and s Participants Patients with COPD according to GOLD ( Global Initiative for COPD ) criteria . Exclusion criteria were terminal illness , cognitive impairment , alcohol or drug misuse , and inability to fill in Dutch question naires . Practice s were included if they were willing to create a multidisciplinary COPD team . Intervention General practitioners , practice nurses , and specialised physiotherapists in the intervention group received a two day training course on incorporating integrated disease management in practice , including early recognition of exacerbations and self management , smoking cessation , physiotherapeutic reactivation , optimal diagnosis , and drug adherence . Additionally , the course served as a network platform and collaborating healthcare providers design ed an individual practice plan to integrate integrated disease management into daily practice . The control group continued usual care ( based on international guidelines ) . Main outcome measures The primary outcome was difference in health status at 12 months , measured by the Clinical COPD Question naire ( CCQ ) ; quality of life , Medical Research Council dyspnoea , exacerbation related outcomes , self management , physical activity , and level of integrated care ( PACIC ) were also assessed as secondary outcomes . Results Of a total of 1086 patients from 40 clusters , 20 practice s ( 554 patients ) were r and omly assigned to the intervention group and 20 clusters ( 532 patients ) to the usual care group . No difference was seen between groups in the CCQ at 12 months ( mean difference –0.01 , 95 % confidence interval –0.10 to 0.08 ; P=0.8 ) . After 12 months , no differences were seen in secondary outcomes between groups , except for the PACIC domain “ follow-up/coordination ” ( indicating improved integration of care ) and proportion of physically active patients . Exacerbation rates as well as number of days in hospital did not differ between groups . After 24 months , no differences were seen in outcomes , except for the PACIC follow-up/coordination domain . Conclusion In this pragmatic study , an integrated disease management approach delivered in primary care showed no additional benefit compared with usual care , except improved level of integrated care and a self reported higher degree of daily activities . The contradictory findings to earlier positive studies could be explained by differences between interventions ( provider versus patient targeted ) , selective reporting of positive trials , or little room for improvement in the already well developed Dutch healthcare system . Trial registration Netherl and s Trial Register NTR2268 BACKGROUND Improving a patient 's ability to self-monitor and manage changes in chronic obstructive pulmonary disease ( COPD ) symptoms may improve outcomes . OBJECTIVE To determine the efficacy of a comprehensive care management program ( CCMP ) in reducing the risk for COPD hospitalization . DESIGN A r and omized , controlled trial comparing CCMP with guideline -based usual care . ( Clinical Trials.gov registration number : NCT00395083 ) SETTING : 20 Veterans Affairs hospital-based outpatient clinics . PARTICIPANTS Patients hospitalized for COPD in the past year . INTERVENTION The CCMP included COPD education during 4 individual sessions and 1 group session , an action plan for identification and treatment of exacerbations , and scheduled proactive telephone calls for case management . Patients in both the intervention and usual care groups received a COPD informational booklet ; their primary care providers received a copy of COPD guidelines and were advised to manage their patients according to these guidelines . Patients were r and omly assigned , stratifying by site based on r and om , permuted blocks of variable size . MEASUREMENTS The primary outcome was time to first COPD hospitalization . Staff blinded to study group performed telephone-based assessment of COPD exacerbations and hospitalizations , and all hospitalizations were blindly adjudicated . Secondary outcomes included non- COPD health care use , all-cause mortality , health-related quality of life , patient satisfaction , disease knowledge , and self-efficacy . RESULTS Of the eligible patients , 209 were r and omly assigned to the intervention group and 217 to the usual care group . Citing serious safety concerns , the data monitoring committee terminated the intervention before the trial 's planned completion after 426 ( 44 % ) of the planned total of 960 patients were enrolled . Mean follow-up was 250 days . When the study was stopped , the 1-year cumulative incidence of COPD -related hospitalization was 27 % in the intervention group and 24 % in the usual care group ( hazard ratio , 1.13 [ 95 % CI , 0.70 to 1.80 ] ; P= 0.62 ) . There were 28 deaths from all causes in the intervention group versus 10 in the usual care group ( hazard ratio , 3.00 [ CI , 1.46 to 6.17 ] ; P= 0.003 ) . Cause could be assigned in 27 ( 71 % ) deaths . Deaths due to COPD accounted for the largest difference : 10 in the intervention group versus 3 in the usual care group ( hazard ratio , 3.60 [ CI , 0.99 to 13.08 ] ; P= 0.053 ) . LIMITATIONS Available data could not fully explain the excess mortality in the intervention group . Ability to assess the quality of the educational sessions provided by the case managers was limited . CONCLUSION A CCMP in patients with severe COPD had not decreased COPD -related hospitalizations when the trial was stopped prematurely . The CCMP was associated with unanticipated excess mortality , results that differ markedly from similar previous trials . A data monitoring committee should be considered in the design of clinical trials involving behavioral interventions There is an urgent need for consensus on what defines a chronic obstructive pulmonary disease ( COPD ) self-management intervention . We aim ed to obtain consensus regarding the conceptual definition of a COPD self-management intervention by engaging an international panel of COPD self-management experts using Delphi technique features and an additional group meeting . In each consensus round the experts were asked to provide feedback on the proposed definition and to score their level of agreement ( 1=totally disagree ; 5=totally agree ) . The information provided was used to modify the definition for the next consensus round . Thematic analysis was used for free text responses and descriptive statistics were used for agreement scores . In total , 28 experts participated . The consensus round response rate varied r and omly over the five rounds ( ranging from 48 % ( n=13 ) to 85 % ( n=23 ) ) , and mean definition agreement scores increased from 3.8 ( round 1 ) to 4.8 ( round 5 ) with an increasing percentage of experts allocating the highest score of 5 ( round 1 : 14 % ( n=3 ) ; round 5 : 83 % ( n=19 ) ) . In this study we reached consensus regarding a conceptual definition of what should be a COPD self-management intervention , clarifying the requisites for such an intervention . Operationalisation of this conceptual definition in the near future will be an essential next step . Consensus of a conceptual definition of what should be a COPD self-management intervention with its requisites Background There have been no r and omised controlled trials that specifically evaluate the effect of a comprehensive programme with multidisciplinary input on patients who have just been discharged from hospital after treatment of acute exacerbation of COPD ( AE COPD ) . The aim of this study was to assess whether a comprehensive care programme would decrease hospital readmissions and length of hospital stay ( LOS ) for patients with COPD . Methods Patients discharged from hospital after an episode of AE COPD were r and omised to an intervention group ( IG ) or usual care group ( UG ) . The IG received a comprehensive , individualised care plan which included education from a respiratory nurse , physiotherapist support for pulmonary rehabilitation , 3-monthly telephone calls by a respiratory nurse over 1 year , and follow-up at a respiratory clinic with a respiratory specialist once every 3 months for 1 year . The UG were managed according to st and ard practice . The primary outcome was hospital readmission rate at 12 months . Results 180 patients were recruited ( IG , N=90 ; UG , N=90 ; mean±SD age 74.7±8.2 years , 172 ( 95.6 % ) men ; mean±SD FEV1 45.4±16.6 % predicted ) . At 12 months , the adjusted relative risk of readmission was 0.668 ( 95 % CI 0.449 to 0.995 , p=0.047 ) for the IG compared with the UG . At 12 months , the IG had a shorter LOS ( 4.59±7.16 vs 8.86±10.24 days , p≤0.001 ) , greater improvement in mean Modified Medical Research Council Dyspnoea Scale ( −0.1±0.6 vs 0.2±0.6 , p=0.003 ) and St George 's Respiratory Question naire score ( −6.9±15.3 vs −0.1±13.8 , p=0.003 ) compared with the UG . Conclusions A comprehensive COPD programme can reduce hospital readmissions for COPD and LOS , in addition to improving symptoms and quality of life of the patients . Trial registration number NCT 01108835 , Results Abstract Objective To evaluate the effectiveness of telephone health coaching delivered by a nurse to support self management in a primary care population with mild symptoms of chronic obstructive pulmonary disease ( COPD ) . Design Multicentre r and omised controlled trial . Setting 71 general practice s in four areas of Engl and . Participants 577 patients with Medical Research Council dyspnoea scale scores of 1 or 2 , recruited from primary care COPD registers with spirometry confirmed diagnosis . Patients were r and omised to telephone health coaching ( n=289 ) or usual care ( n=288 ) . Interventions Telephone health coaching intervention delivered by nurses , underpinned by Social Cognitive Theory . The coaching promoted accessing smoking cessation services , increasing physical activity , medication management , and action planning ( 4 sessions over 11 weeks ; postal information at weeks 16 and 24 ) . The nurses received two days of training . The usual care group received a leaflet about COPD . Main outcome measures The primary outcome was health related quality of life at 12 months using the short version of the St George ’s Respiratory Question naire ( SGRQ-C ) . Results The intervention was delivered with good fidelity : 86 % of scheduled calls were delivered ; 75 % of patients received all four calls . 92 % of patients were followed-up at six months and 89 % at 12 months . There was no difference in SGRQ-C total score at 12 months ( mean difference −1.3 , 95 % confidence interval −3.6 to 0.9 , P=0.23 ) . Compared with patients in the usual care group , at six months follow-up , the intervention group reported greater physical activity , more had received a care plan ( 44 % v 30 % ) , rescue packs of antibiotics ( 37 % v 29 % ) , and inhaler use technique check ( 68 % v 55 % ) . Conclusions A new telephone health coaching intervention to promote behaviour change in primary care patients with mild symptoms of dyspnoea did lead to changes in self management activities , but did not improve health related quality of life . Trial registration Current controlled trials IS RCT N Background : More evidence is needed about factors that influence self‐management behaviors in persons with heart failure . Objective : To test a correlational mediation model of the independent variables of health literacy , patient activation , and heart failure knowledge with heart failure self‐management behaviors . Methods : The study used a prospect i ve , cross‐sectional , correlational design . Correlation and multiple regression were used to analyze associations among variables . Results : Of 151 participants , 57 % were male , and mean age was 68 years . Heart failure self‐management behaviors was positively correlated with patient activation level ( p = .0008 ) , but not with health literacy or heart failure knowledge . Conclusions : Persons with heart failure may better manage their condition if sufficiently activated , regardless of their level of health literacy or knowledge of heart failure disease and management processes Rationale : Socioeconomically disadvantaged patients with chronic obstructive pulmonary disease ( COPD ) often face barriers to evidence ‐based care that are difficult to address in public care setting s with limited re sources . Objectives : To determine the benefit of health coaching for patients with moderate to severe COPD relative to usual care . Methods : We conducted a r and omized controlled trial of 9 months of health coaching versus usual care for English‐ or Spanish‐speaking patients at least 40 years of age with moderate to severe COPD . Primary outcomes were COPD ‐related quality of life and the dyspnea subscale of the Chronic Respiratory Disease Question naire . Secondary outcomes were self‐efficacy for managing COPD , exercise capacity ( 6‐min walk test ) , and number of COPD exacerbations . Additional outcomes were COPD symptoms , lung function ( forced expiratory volume in 1 s percent predicted ) , smoking status , bed days owing to COPD , quality of care ( Patient Assessment of Chronic Illness Care ) , COPD knowledge , and symptoms of depression ( Patient Health Question naire ) . Outpatient visits , emergency department visits , and hospitalizations were assessed by review of medical records . Generalized linear modeling was used to adjust for baseline values and account for clustering by clinic . Results : Of 192 patients enrolled , 158 ( 82 % ) completed 9 months of follow‐up . There were no significant differences between study arms for the primary or secondary outcomes . At 9 months , patients in the coached group reported better quality of care ( mean Patient Assessment of Chronic Illness Care score , 3.30 vs. 3.18 ; adjusted P = 0.02 ) and were less likely to report symptoms of moderate to severe depression ( Patient Health Question naire score , ≥15 ) than those in the usual care arm ( 6 % vs. 20 % ; adjusted P = 0.01 ) . During the study , patients in the coaching arm had 48 % fewer hospitalizations related to COPD ( 0.27/patient/yr vs. 0.52/patient/yr ) , but this difference was not significant in the adjusted analysis . Conclusions : These results help inform expectations regarding the limitations and benefits of health coaching for patients with COPD . They may be useful to health policy experts in assessing the potential value of reimbursement and incentives for health coaching‐type activities for patients with chronic disease . Clinical trial registered with www . clinical trials.gov ( NCT02234284 ) Background This study examines the effects of the COPD -specific health promoting self-management intervention “ Better living with COPD ” on different self-management-related domains , self-efficacy , and sense of coherence ( SOC ) . Methods In a r and omized controlled design , 182 people with COPD were allocated to either an intervention group ( offered Better living with COPD in addition to usual care ) or a control group ( usual care ) . Self-management-related domains were measured by the Health Education Impact Question naire ( heiQ ) before and after intervention . Self-efficacy was measured by the General Self-Efficacy Scale ( GSE ) and SOC was measured by the 13-item Sense of Coherence Scale ( SOC-13 ) . Effects were assessed by ANCOVA , using intention-to-treat ( ITT ) analysis and per- protocol analysis ( PPA ) . Results The PPA and the ITT analysis showed significant positive changes on Constructive attitudes and approaches ( heiQ ) ( ITT : P=0.0069 ; PPA : P=0.0021 ) and Skill and technique acquisition ( heiQ ) ( ITT : P=0.0405 ; PPA : P=0.0356 ) . Self-monitoring and insight ( heiQ ) showed significant positive change in the PPA ( P=0.0494 ) . No significant changes were found on the other self-management domains ( heiQ ) , self-efficacy ( GSE ) , or SOC ( SOC-13 ) . Conclusion Better living with COPD had a significant positive short-term effect on some self-management-related domains , and could be an intervention contributing to the support of self-management in people with COPD . However , further work is needed to establish the clinical relevance of the findings and to evaluate the long-term effects Patients with chronic obstructive pulmonary disease ( COPD ) have a reduced quality of life ( QoL ) and exacerbations that drive health service utilization ( HSU ) . A majority of patients with COPD are managed in primary care . Our objective was to evaluate an integrated disease management , self-management , and structured follow-up intervention ( IDM ) for high-risk patients with COPD in primary care . This was a one-year multi-center r and omized controlled trial . High-risk , exacerbation-prone COPD patients were r and omized to IDM provided by a certified respiratory educator and physician , or usual physician care . IDM received case management , self-management education , and skills training . The primary outcome , COPD -related QoL , was measured using the COPD Assessment Test ( CAT ) . Of 180 patients r and omized from 8 sites , 81.1 % completed the study . Patients were 53.6 % women , mean age 68.2 years , post-bronchodilator FEV1 52.8 % predicted , and 77.4 % were Global Initiative for Obstructive Lung Disease Stage D. QoL-CAT scores improved in IDM patients , 22.6 to 14.8 , and worsened in usual care , 19.3 to 22.0 , adjusted difference 9.3 ( p < 0.001 ) . Secondary outcomes including the Clinical COPD Question naire , Bristol Knowledge Question naire , and FEV1 demonstrated differential improvements in favor of IDM of 1.29 ( p < 0.001 ) , 29.6 % ( p < 0.001 ) , and 100 mL , respectively ( p = 0.016 ) . Compared to usual care , significantly fewer IDM patients had a severe exacerbation , −48.9 % ( p < 0.001 ) , required an urgent primary care visit for COPD , −30.2 % ( p < 0.001 ) , or had an emergency department visit , −23.6 % ( p = 0.001 ) . We conclude that IDM self-management and structured follow-up substantially improved QoL , knowledge , FEV1 , reduced severe exacerbations , and HSU , in a high-risk primary care COPD population . Clinical trials.gov NCT02343055.Chronic lung disease : Integrated care shows promise Patients enrolled on a chronic lung disease care program involving education and self-management report improved quality of life ( QoL ) . People with severe forms of chronic obstructive pulmonary disease ( COPD ) often require urgent treatment for exacerbations and struggle with poor QoL. Christopher Licskai at Western University in Ontario , Canada , and co-workers trialed a one-year integrated disease management ( IDM ) program and compared it with st and ard care in 168 patients with severe COPD in primary care . The IDM involved regular collaboration with health professionals , guidance on best practice with medications , and personalized action plans . All participants completed the COPD Assessment Test , which indicated that IDM patients ’ QoL scores improved during treatment , while QoL of those in st and ard care worsened over time . Significantly fewer IDM patients had severe exacerbations or the need for urgent medical care Background Primary health professionals are well positioned to support the delivery of patient self-management in an evidence -based , structured capacity . A need exists to better underst and the active components required for effective self-management support , how these might be delivered within primary care , and the training and system changes that would subsequently be needed . Objectives ( 1 ) To examine self-management support interventions in primary care on health outcomes for a wide range of diseases compared to usual st and ard of care ; and ( 2 ) To identify the effective strategies that facilitate positive clinical and humanistic outcomes in this setting . Method A systematic review of r and omized controlled trials evaluating self-management support interventions was conducted following the Cochrane h and book & PRISMA guidelines . Published literature was systematic ally search ed from inception to June 2019 in PubMed , Scopus and Web of Science . Eligible studies assessed the effectiveness of individualized interventions with follow-up , delivered face-to-face to adult patients with any condition in primary care , compared with usual st and ard of care . Matrices were developed that mapped the evidence and components for each intervention . The method ological quality of included studies were appraised . Results 6,510 records were retrieved . 58 studies were included in the final qualitative synthesis . Findings reveal a structured patient-provider exchange is required in primary care ( including a one-on-one patient-provider consultation , ongoing follow up and provision of self-help material s ) . Interventions should be tailored to patient needs and may include combinations of strategies to improve a patient ’s disease or treatment knowledge ; independent monitoring of symptoms , encouraging self-treatment through a personalized action plan in response worsening symptoms or exacerbations , psychological coping and stress management strategies , and enhancing responsibility in medication adherence and lifestyle choices . Follow-up may include tailored feedback , monitoring of progress with respect to patient set healthcare goals , or honing problem-solving and decision-making skills . Theoretical models provided a strong base for effective SMS interventions . Positive outcomes for effective SMS included improvements in clinical indicators , health-related quality of life , self-efficacy ( confidence to self-manage ) , disease knowledge or control . An SMS model has been developed which sets the foundation for the design and evaluation of practical strategies for the construct of self-management support interventions in primary healthcare practice . Conclusions These findings provide primary care professionals with evidence -based strategies and structure to deliver SMS in practice . For this collaborative partnership approach to be more widely applied , future research should build on these findings for optimal SMS service design and upskilling healthcare providers to effectively support patients in this collaborative process Importance Patients hospitalized for chronic obstructive pulmonary disease ( COPD ) exacerbations have high rehospitalization rates and reduced quality of life . Objective To evaluate whether a hospital-initiated program that combined transition and long-term self-management support for patients hospitalized due to COPD and their family caregivers can improve outcomes . Design , Setting , and Participants Single-site r and omized clinical trial conducted in Baltimore , Maryl and , with 240 participants . Participants were patients hospitalized due to COPD , r and omized to intervention or usual care , and followed up for 6 months after hospital discharge . Enrollment occurred from March 2015 to May 2016 ; follow-up ended in December 2016 . Interventions The intervention ( n = 120 ) involved a comprehensive 3-month program to help patients and their family caregivers with long-term self-management of COPD . It was delivered by nurses with special training on supporting patients with COPD using st and ardized tools . Usual care ( n = 120 ) included transition support for 30 days after discharge to ensure adherence to discharge plan and connection to outpatient care . Main Outcomes and Measures The primary outcome was number of COPD -related acute care events ( hospitalizations and emergency department visits ) per participant at 6 months . The co- primary outcome was change in participants ' health-related quality of life measured by the St George 's Respiratory Question naire ( SGRQ ) at 6 months after discharge ( score , 0 [ best ] to 100 [ worst ] ; 4-point difference is clinical ly meaningful ) . Results Among 240 patients who were r and omized ( mean [ SD ] age , 64.9 [ 9.8 ] years ; 61.7 % women ) , 203 ( 85 % ) completed the study . The mean ( SD ) baseline SGRQ score was 62.3 ( 18.8 ) in the intervention group and 63.6 ( 17.4 ) in the usual care group . The mean number of COPD -related acute care events per participant at 6 months was 1.40 ( 95 % CI , 1.01 - 1.79 ) in the intervention group vs 0.72 ( 95 % CI , 0.45 - 0.97 ) in the usual care group ( difference , 0.68 [ 95 % CI , 0.22 - 1.15 ] ; P = .004 ) . The mean change in participants ' SGRQ total score at 6 months was 2.81 in the intervention group and -2.69 in the usual care group ( adjusted difference , 5.18 [ 95 % CI , -2.15 to 12.51 ] ; P = .11 ) . During the study period , there were 15 deaths ( intervention : 8 ; usual care : 7 ) and 339 hospitalizations ( intervention : 202 ; usual care : 137 ) . Conclusions and Relevance In a single-site r and omized clinical trial of patients hospitalized due to COPD , a 3-month program that combined transition and long-term self-management support result ed in significantly greater COPD -related hospitalizations and emergency department visits , without improvement in quality of life . Further research is needed to determine reasons for this unanticipated finding . Trial Registration Clinical Trials.gov Identifier : NCT02036294 AIMS To evaluate the effectiveness of a 6-month , partnership-based self-management programme for patients with mild and moderate chronic obstructive pulmonary disease . BACKGROUND Self-management is a widely valued concept used to address contemporary issues of chronic health problems . Findings of self-management programmes for people with chronic obstructive pulmonary disease are inconclusive . DESIGN Pragmatic r and omized control trial . METHODS Patients , 45 - 65 years old , with mild and moderate chronic obstructive pulmonary disease were invited with a family member . Experimental group ( n = 48 ) participated in a 6-month , partnership-based self-management programme consisting of : ( a ) three to four conversations between nurse and patient-family member ; ( b ) 6 months of smoking cessation ; and ( c ) interdisciplinary team-patient-family member group meeting . Control group ( n = 52 ) received usual care . Data were collected at months zero , six and 12 . The trial lasted from June 2009-March 2013 . RESULTS Patients with mild and moderate chronic obstructive pulmonary disease who participated in the partnership-based self-management programme perceived less intrusiveness of the disease and its treatment than patients in the control group . Patients in the experimental group did not have better health-related quality of life , less anxiety or depression , increased physical activity , fewer exacerbations or better smoking status than patients in the control group . Patients in both groups found participation in the research useful and important . CONCLUSION The partnership-based self-management programme had benefits concerning perception of the intrusiveness of chronic obstructive pulmonary disease and its treatment on lifestyles , activities and interests for young patients with the disease in its early stages . High satisfaction in control group , low family attendance and the relatively short treatment period may explain the less than expected benefits of the programme UNLABELLED AIM D : To assess the long-term effectiveness of an integrated disease management ( IDM ) program ( consisting of optimal medication , reactivation , education , and exacerbation management ) in primary care patients with chronic obstructive pulmonary disease ( COPD ) . METHOD Controlled trial comparing the effects of IDM on quality of life -- assessed by the St. George 's Respiratory Question naire (SGRQ)--in primary care COPD patients . The minimal clinical ly important change on the SGRQ was accepted as being -4 points . Baseline and one year differences were compared using paired sample T-tests . The differential effects of an FEV1/FVC ratio < 0.7 and dyspnoea as assessed by the Medical Research Council ( MRC ) Dyspnoea scale were investigated . RESULTS The average age of subjects was 63 years , with an average post-bronchodilator FEV1 of 67 % predicted , average FEV1/FVC ratio of 0.65 , a mean of 35 pack-years smoking , and 63 % were male . No significant differences existed between groups at baseline . After one year of IDM , SGRQ had improved by -4.6 points ( 95 % CI , -7.2 to -2.0 ; p=0.001 ) in the intervention group , versus -0.7 points ( 95 % CI , - 3.0 to 1.6 ; p=0.6 ) in the usual care group . In patients with an FEV1/FVC ratio < 0.7 , SGRQ improved by -5.9 points ( 95 % CI , -9.6 to -2.2 ; p=0.002 ) in the IDM group , while in the usual care group SGRQ improved by -0.8 points ( 95 % CI , -4.1 to 2.4 ; p=0.6 ) . In patients with an MRC Dyspnoea score > 2 and FEV1/FVC < 0.7 , SGRQ improved by -13.4 points ( 95 % CI , -20.8 to -6.1 ; p=0.002 ) in the IDM group , versus -0.3 points ( 95 % CI , -5.5 to 4.9 ; p=0.9 ) in the usual care group . CONCLUSION In this study , IDM improved one-year quality of life in primary care COPD patients , compared to usual care . The improvement in SGRQ was both clinical ly relevant and statistically significant , and was greatest in patients with FEV1/FVC < 0.7 and MRC Dyspnoea score > 2 PURPOSE To examine the effectiveness of a nurse-led self-management program on outcomes of patients with chronic obstructive pulmonary disease ( COPD ) . DESIGN A r and omized controlled , single blind trial , carried out from October 2017 to December 2018 , included 154 participants admitted with COPD to the Affiliated Hospital of Zunyi Medical University in Guizhou , ( r and omized into intervention ( n=77 ) and control groups ( n=77 ) ) . METHODS Participants in the intervention group underwent a nurse-led self-management program in addition to routine care , and participants of the control group received only routine care . The main outcome measures were COPD -related readmission and emergency department visits , the 6-minute walk distance ( 6MWD ) test for measurement of exercise capacity , the St George Respiratory Question naire ( SGRQ ) for measurement of health-related quality of life , and the COPD Transitional Care Patient Satisfaction Question naire ( CTCPSQ ) for measurement of satisfaction . Data collection was conducted at baseline ( T1 ) and after 3 ( T2 ) , 6 ( T3 ) and 12 months ( T4 ) . FINDINGS Compared to the control group , participants in the intervention group showed significantly fewer COPD -related hospital admissions ( P = 0.03 ) and emergency department visits ( P = 0.001 ) and higher total CTCPSQ scores ( P = 0.001 ) at 12 months . Meanwhile , analysis of variance showed a significantly greater improvement in exercise capacity and health status over time in the nurse-led program group than in the control group , p<0.001 . CONCLUSIONS This study demonstrated that the nurse-led self-management program was effective in decreasing hospital readmissions and emergency department visits and improving exercise capacity , health-related quality of life , and satisfaction for patients with COPD |
12,858 | 23,279,674 | CONCLUSION The available evidence suggests that use of ACE inhibitors and angiotensin 2 receptor antagonists or thiazide diuretics have the potential to reduce zinc levels in hypertensive patients . | BACKGROUND Antihypertensive medicines are to known to cause diverse disturbances to electrolyte homeostasis ; however , their potential to affect zinc is less well known .
The primary aim was to explore whether antihypertensive medicines have the potential to affect zinc status . | We studied the influence of captopril , atenolol , and verapamil on serum and intraerythrocyte concentrations of magnesium and zinc in 30 normotensive control subjects ( 12 men and 18 women , aged 30 to 65 years , mean + /- SD 45.76 + /- 12.15 years ) and 30 patients with untreated mild or moderate essential hypertension ( 14 men and 16 women , aged 30 to 65 years , mean + /- SD 49.50 + /- 13.58 years ) . Ten each of the hypertensive patients were treated with captopril , atenolol , or verapamil . Physical examination and biochemical analyses ( serum Mg and Zn ) were done in all participants at baseline , and in patients after 3 and 6 months of treatment . The results were compared according to a nested design with Neumann-Keuls test . We found no significant differences between controls and patients in serum and intraerythrocyte concentrations of Zn at the start of the study , although there was a significant decrease in serum Zn in patients after 3 ( P < .01 ) and 6 months ( P < .001 ) of treatment , regardless of the drug used . This decrease was thought to be attributable to the zincuric effect of captopril or to dietary measures , or both . Intraerythrocyte Zn was not significantly affected by antihypertensive treatment . Serum and intraerythrocyte concentrations of Mg were significantly lower ( P < .001 ) in hypertensive than in normotensive subjects , and serum Mg in patients treated with verapamil was significantly lower ( P < .05 ) than after treatment with captopril or atenolol . Serum Mg concentration was related directly with serum concentrations of high density lipoprotein cholesterol ( r = 0.4043 , P < .05 ) . We conclude that supplementation with Mg may benefit patients with hypertension Urinary zinc excretion was studied in a r and omized trial in 9 patients during treatment with bendroflumethiazide , chlorthalidone and hydrochlorothiazide and in another 9 patients during treatment with bumetanide , furosemide and triamterene . During treatment with the thiazides , the zinc concentration rose by 30 % and the total amount of zinc excretion increased by 60 % . In contrast , during treatment with the loop-diuretics , urine zinc concentration diminished and the total amount of zinc excretion increased much less than during therapy with the thiazides . With respect to the importance of zinc as an essential element in human metabolism and the frequency of diuretic treatment , the observed increased urinary losses of zinc deserve further attention Background Free oxygen radicals and insufficiency of antioxidant enzymes have been implicated in the pathogenesis of hypertension disease ( HD ) . Trace elements function as a co-factor in antioxidant enzymes . The antioxidant system and trace elements have been investigated in many different studies including HD , but these subjects have not been investigated as a whole in these patients . Objective The aim of the present study was to investigate the antioxidative system and trace elements in hypertensive patients given different antihypertensive therapy . Methods We examined malondialdehyde and superoxide dismutase activities together with copper and zinc levels in plasma of 102 patients with HD and in 51 healthy controls . Results It was found that in patients with HD , plasma malondialdehyde was significantly higher than those of controls , while plasma superoxide dismutase activities were significantly lower in patients with HD . Plasma zinc levels were significantly higher than those of controls and plasma copper levels were significantly lower in patients with HD . Plasma lipid levels and oxidative state were analyzed in five different treatment groups given antihypertensive drug therapy before and after a 3-month treatment period . Conclusions In conclusion , our clinical study shows that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers have notable effects on oxidative stress , and are an essential step in managing essential hypertension by the way of improvement of endothelial dysfunction . Although it has been shown that calcium channel blockers , beta blockers and alpha receptor blockers have antioxidant effects in in vitro conditions , we did not demonstrate these effects in our clinical study This study was design ed to test the hypothesis that hydrochlorothiazide a diuretic used to treat hypertension depletes body zinc and thereby cause sexual dysfunction . Serum zinc and sexual dysfunction were measured in 39 middle aged hypertensive men who had been taking hydrochlorothiazide in average daily doses of between 25 and 50 mg daily for at least six months , and a control group of 27 unmedicated middle aged normotensive men . The medicated group had a higher incidence of sexual dysfunction ( 56 pc ) as compared to 11 pc in the control group . The use of hydrochlorothiazide did affect serum zinc levels significantly in 20 patients . Sexual dysfunction occurred more often in older and overweight patients ( p < 0.004 ) . Three of the normotensive men experienced sexual dysfunction probably related to old age . Twenty two of the 39 on hydrochlorothiazide and experiencing sexual dysfunction were divided into two groups of 11 patients . Bloods were taken from the 27 normotensive and 22 hypertensive men receiving hydrochlorothiazide for the analyses of zinc . Subsequently one group of the patients were supplemented with zinc 500 mg daily for 30 days while the other group was supplemented with magnesium chloride 1 g daily for 30 days . The normotensive men were not treated . After 30 days , bloods were again taken from the three groups of analyses for zinc and magnesium . Serum zinc was significantly decreased ( p < 0.05 ) by hydrochlorothiazide and a non significant decrease in serum magnesium ( p = ns ) was observed . After supplementation with zinc , the serum zinc levels returned to normal only in eight patients . There was improvement in the symptoms of sexual dysfunction in five patients . Two patients gained weight . Hydrochlorothiazide decreased serum zinc levels ( p < 0.05 ) and was unchanged with magnesium supplementation but the serum magnesium returned to normal values . Improvement of symptoms of sexual dysfunction was positive in one patient . This study shows that low serum zinc levels may be associated with sexual dysfunction but the definitive role of zinc in the pathogenesis of sexual dysfunction will remain controversial |
12,859 | 25,258,511 | This weight reduction is moderate but similar to other antiobesity drugs . | Obesity is an emerging disease worldwide .
Changes in living habits , especially with increased consumption of high-calorie foods and decreased levels of physical activity , lead to an energy imbalance that brings weight gain .
Overweight and obesity are major risk factors for several chronic diseases ( including cardiovascular diseases , diabetes , and cancer ) , reduce quality of life , and are associated with higher mortality .
For all these reasons , it is of the utmost importance that the trend be reversed and obese people enabled to lose weight .
It is known that eating a healthy diet and exercising regularly can help prevent obesity , but data show that in many cases these steps are not enough .
This is the reason why , over the last few decades , several antiobesity drugs have been developed .
However , the disappointing results demonstrated for the vast majority of them have not discouraged the pharmaceutical industry from continuing to look for an effective drug or combination of drugs .
The systematic review presented here focuses on naltrexone sustained-release/bupropion sustained-release combination ( Contrave ( ® ) ) . | This 56-week , r and omized , placebo-controlled trial examined the efficacy and safety of naltrexone plus bupropion as an adjunct to intensive behavior modification ( BMOD ) . A total of 793 participants ( BMI = 36.5 ± 4.2 kg/m² ) was r and omly assigned in a 1:3 ratio to : ( i ) placebo + BMOD ( N = 202 ) ; or ( ii ) naltrexone sustained-release ( SR , 32 mg/day ) , combined with bupropion SR ( 360 mg/day ) plus BMOD ( i.e. , NB32 + BMOD ; N = 591 ) . Both groups were prescribed an energy-reduced diet and 28 group BMOD sessions . Co- primary end points were percentage change in weight and the proportion of participants who lost ≥5 % weight at week 56 . Efficacy analyses were performed on a modified intent-to-treat population ( ITT ; i.e. , participants with ≥1 postbaseline weight while taking study drug ( placebo + BMOD , N = 193 ; NB32 + BMOD , N = 482 ) ) . Missing data were replaced with the last observation obtained on study drug . At week 56 , weight loss was 5.1 ± 0.6 % with placebo + BMOD vs. 9.3 ± 0.4 % with NB32 + BMOD ( P < 0.001 ) . A completers analysis revealed weight losses of 7.3 ± 0.9 % ( N = 106 ) vs. 11.5 ± 0.6 % ( N = 301 ) , respectively ( P < 0.001 ) . A third analysis , which included all r and omized participants , yielded losses of 4.9 ± 0.6 vs. 7.8 ± 0.4 % , respectively ( P < 0.001 ) . Significantly more NB32 + BMOD- vs. placebo + BMOD-treated participants lost ≥5 and ≥10 % of initial weight , and the former had significantly greater improvements in markers of cardiometabolic disease risk . NB32 + BMOD was generally well tolerated , although associated with more reports of nausea than placebo + BMOD . The present findings support the efficacy of combined naltrexone/bupropion therapy as an adjunct to intensive BMOD for obesity To investigate the effects of the long-acting opiate antagonist naltrexone on spontaneous human eating behavior , eight moderately obese male paid volunteers were housed in a hospital metabolic unit for 28 days and offered palatable foods ad lib by a platter service method . Under double-blind conditions , equally divided doses of 100 , 200 and 300 mg naltrexone , or an acetaminophen placebo , were administered twice daily in tablet form for 3-day periods each , according to a Latin Square design . The doses of naltrexone result ed in decreases of daily caloric intake from placebo level , but these reductions were neither statistically significant nor dose-related . When the averaged effects of the doses were compared to placebo , five subjects showed intake reductions but the overall intake reduction of 301.5 + /- 198.1 kcal/day ( mean + /- SEM ) was not statistically significant . Naltrexone administration failed to selectively alter intakes of individual meals and snacks or macronutrient consumption patterns . During active drug periods , subjects lost 0.62 + /- 0.22 lb over 3 days , while during the placebo period , subjects gained 0.46 + /- 0.68 lb . However , there was no reliable change of basal metabolic rate as a function of naltrexone administration . The present results , which indicate that naltrexone administration is relatively ineffective in reducing food intake and inducing body weight loss in obese humans , are thus in contrast with reports that administration of opiate antagonist agents promote significant reductions of food intake and attenuations of body weight gain in experimental animals Objective To examine the effects of naltrexone/bupropion ( NB ) combination therapy on weight and weight-related risk factors in overweight and obese participants . Design and Methods CONTRAVE Obesity Research -II ( COR-II ) was a double-blind , placebo-controlled study of 1,496 obese ( BMI 30 - 45 kg/m2 ) or overweight ( 27 - 45 kg/m2 with dyslipidemia and /or hypertension ) participants r and omized 2:1 to combined naltrexone sustained-release ( SR ) ( 32 mg/day ) plus bupropion SR ( 360 mg/day ) ( NB32 ) or placebo for up to 56 weeks . The co- primary endpoints were percent weight change and proportion achieving ≥5 % weight loss at week 28 . Results Significantly ( P < 0.001 ) greater weight loss was observed with NB32 versus placebo at week 28 ( −6.5 % vs. −1.9 % ) and week 56 ( −6.4 % vs. −1.2 % ) . More NB32-treated participants ( P < 0.001 ) experienced ≥5 % weight loss versus placebo at week 28 ( 55.6 % vs. 17.5 % ) and week 56 ( 50.5 % vs. 17.1 % ) . NB32 produced greater improvements in various cardiometabolic risk markers , participant-reported weight-related quality of life , and control of eating . The most common adverse event with NB was nausea , which was generally mild to moderate and transient . NB was not associated with increased events of depression or suicidality versus placebo . Conclusion NB represents a novel pharmacological approach to the treatment of obesity , and may become a valuable new therapeutic option A combination of sustained release ( SR ) naltrexone ( 32 mg/day ) and bupropion SR ( 360 mg/day ) plus behavioral counseling was evaluated for the treatment of smoking cessation and mitigation of nicotine withdrawal and weight gain . Thirty overweight or obese nicotine-dependent subjects were enrolled in a 24-week , open-label study ; 85 % and 63 % completed 12 and 2 4weeks , respectively . The target quit date was Week 4 . Week 4 - 12 continuous abstinence rate was 48 % , 78 % of subjects achieved CO < or = 10 ppm , serum cotinine decreased from 185 to 48 microg/L , and tobacco use decreased from 129 to 14 cigarettes/week . Similar results were seen at Week 24 . Body weight was essentially unchanged ( Week 12 : -0.1 % ; Week 24 : + 0.4 % ) . Except for a transient significant increase 1 week after the target quit date ( p<0.05 ) , nicotine withdrawal scores did not change . The most common adverse events were nausea , insomnia , and constipation . These tended to be transient and mild or moderate in severity . In overweight or obese smokers , naltrexone/bupropion combination therapy with behavioral counseling was associated with decreased nicotine use , limited nicotine withdrawal symptoms , and no significant weight gain Eight healthy nonobese volunteers were asked to rate , on a pleasure-displeasure scale , sucrose and salty solutions as well as alimentary and nonalimentary odors . Effects of intragastric glucose load ( vs. water load ) and naltrexone ( vs. placebo ) were tested . Naltrexone produces a significant decrease for sweetened solution on the pleasure scale , a shift even stronger than that of the glucose load itself . Such a decrease is also observed for alimentary odors but not for responses to nonalimentary stimuli . Thus the opioid system is involved in ingestive behavior in humans , and this action is perhaps specific Existing obesity therapies are limited by safety concerns and modest efficacy reflecting a weight loss plateau . Here , we explore combination therapy with bupropion ( BUP ) , a putative stimulator of melanocortin pathways , and an opioid antagonist , naltrexone ( NAL ) , to antagonize an inhibitory feedback loop that limits sustained weight reduction . In vitro electrophysiologic experiments were conducted to determine the extent to which BUP+NAL stimulated hypothalamic pro-opiomelanocortin ( POMC ) neurons in mouse brain . A subsequent study further characterized the effect of combination BUP+NAL treatment on food intake in lean and obese mice . Finally , a r and omized , blinded , placebo-controlled trial in obese adult subjects was conducted . R and omization included : BUP ( 300 mg ) + NAL ( 50 mg ) , BUP ( 300 mg ) + placebo ( P ) , NAL ( 50 mg ) + P or P+P for up to 24 weeks . BUP+NAL stimulated murine POMC neurons in vitro and caused a greater reduction in acute food intake than either monotherapy , an effect consistent with synergism . Combined BUP+NAL provided sustained weight loss without evidence of an efficacy plateau through 24 weeks of treatment . BUP+NAL completers diverged from NAL+P ( P < 0.01 ) and P+P ( P < 0.001 ) at week 16 and from BUP+P by week 24 ( P < 0.05 ) . The combination was also well tolerated . Translational studies indicated that BUP+NAL therapy produced synergistic weight loss which exceeded either BUP or NAL alone . These results supported the hypothesis that NAL , through blockade of beta-endorphin mediated POMC autoinhibition , prevents the classic weight loss plateau observed with monotherapies such as BUP . This novel treatment approach ( BUP+NAL ) holds promise for the treatment of Based on reports that opiate antagonists can curtail short-term eating in several species including humans , the efficacy of naltrexone in promoting weight loss by obese subjects was examined . Naltrexone , a long-acting oral opiate antagonist , was studied in a r and omized parallel double-blind placebo controlled ten week trial in 27 females and 14 males who were 30 - 100 percent overweight . Subjects on naltrexone lost an average of 1.8 kg and placebo subjects lost 1.5 kg , with no significant difference between groups . Three subjects who took naltrexone had elevations of liver transaminases , two times higher than normal . In the present study naltrexone at a daily dosage of 200 mg did not appear to have efficacy in producing weight loss after eight weeks of treatment . Studies of the effects of naltrexone at higher dosage or for longer periods should monitor hepatic function OBJECTIVE To critically examine the efficacy of bupropion SR for weight loss . RESEARCH METHODS AND PROCEDURES This 24-week multicenter , double-blind , placebo-controlled study r and omized obese adults to placebo , bupropion SR 300 , or 400 mg/d . Subjects were counseled on energy-restricted diets , meal replacements , and exercise . During a 24-week extension , placebo subjects were r and omized to bupropion SR 300 or 400 mg/d in a double-blinded manner . RESULTS Of 327 subjects enrolled , 227 completed 24 weeks ; 192 completed 48 weeks . Percentage losses of initial body weight for subjects completing 24 weeks were 5.0 % , 7.2 % , and 10.1 % for placebo , bupropion SR 300 , and 400 mg/d , respectively . Compared with placebo , net weight losses were 2.2 % ( p = 0.0468 ) and 5.1 % ( p < 0.0001 ) for bupropion SR 300 and 400 mg/d , respectively . The percentages of subjects who lost > or=5 % of initial body weight were 46 % , 59 % , and 83 % ( p vs. placebo < 0.0001 ) for placebo , bupropion SR 300 , and 400 mg/d , respectively ; weight losses of > or=10 % were 20 % , 33 % , and 46 % ( p vs. placebo = 0.0008 ) for placebo , bupropion SR 300 , and 400 mg/d , respectively . Withdrawals , changes in pulse and blood pressure did not differ significantly from placebo at 24 weeks . Subjects who completed 48 weeks maintained mean losses of initial body weight of 7.5 % and 8.6 % for bupropion SR 300 and 400 mg/d , respectively . DISCUSSION Bupropion SR 300 and 400 mg/d were well-tolerated by obese adults and were associated with a 24-week weight loss of 7.2 % and 10.1 % and sustained weight losses at 48 weeks BACKGROUND Despite increasing public health concerns regarding obesity , few safe and effective drug treatments are available . Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight . The Contrave Obesity Research I ( COR-I ) study assessed the effect of such treatment on bodyweight in overweight and obese participants . METHODS Men and women aged 18 - 65 years who had a body-mass index ( BMI ) of 30 - 45 kg/m(2 ) and uncomplicated obesity or BMI 27 - 45 kg/m(2 ) with dyslipidaemia or hypertension were eligible for enrolment in this r and omised , double-blind , placebo-controlled , phase 3 trial undertaken at 34 sites in the USA . Participants were prescribed mild hypocaloric diet and exercise and were r and omly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets ( also known as NB32 ) , sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets ( also known as NB16 ) , or matching placebo twice a day , given orally for 56 weeks . The trial included a 3-week dose escalation . R and omisation was done by use of a central ised , computer-generated , web-based system and was stratified by study centre . Co- primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5 % or more . The primary analysis included all r and omised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug ( last observation carried forward ) . This study is registered with Clinical Trials.gov , number NCT00532779 . FINDINGS 1742 participants were enrolled and r and omised to double-blind treatment ( naltrexone 32 mg plus bupropion , n=583 ; naltrexone 16 mg plus bupropion , n=578 ; placebo , n=581 ) . 870 ( 50 % ) participants completed 56 weeks of treatment ( n=296 ; n=284 ; n=290 , respectively ) and 1453 ( 83 % ) were included in the primary analysis ( n=471 ; n=471 ; n=511 ) . Mean change in bodyweight was -1.3 % ( SE 0.3 ) in the placebo group , -6.1 % ( 0.3 ) in the naltrexone 32 mg plus bupropion group ( p<0.0001 vs placebo ) and -5.0 % ( 0.3 ) in the naltrexone 16 mg plus bupropion group ( p<0.0001 vs placebo ) . 84 ( 16 % ) participants assigned to placebo had a decrease in bodyweight of 5 % or more compared with 226 ( 48 % ) assigned to naltrexone 32 mg plus bupropion ( p<0.0001 vs placebo ) and 186 ( 39 % ) assigned to naltrexone 16 mg plus bupropion ( p<0.0001 vs placebo ) . The most frequent adverse event in participants assigned to combination treatment was nausea ( naltrexone 32 mg plus bupropion , 171 participants [ 29.8 % ] ; naltrexone 16 mg plus bupropion , 155 [ 27.2 % ] ; placebo , 30 [ 5.3 % ] ) . Headache , constipation , dizziness , vomiting , and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group . A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups . Combination treatment was not associated with increased depression or suicidality events compared with placebo . INTERPRETATION A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity . FUNDING Orexigen Therapeutics There is considerable evidence that antagonism of the endogenous opioids will suppress food intake in a variety of animal species . The authors report a double-blind , placebo-controlled trial of the long-acting , orally active narcotic antagonist naltrexone in the promotion of weight loss in obese male subjects who were also undergoing dietary counseling for weight reduction . Subjects received medication ( naltrexone , 300 mg/day or placebo ) for 8 weeks following an initial 2-week single-blind placebo phase . The results failed to demonstrate an advantage for the active drug . However , the naltrexone was associated with hepatotoxicity when used at this dosage in this population The endogenous opiate system is thought to be associated with the regulation of food intake and body weight . Opiate antagonists decrease food intake in animals , but there are no controlled studies in obese man to evaluate body weight response to naltrexone . Sixty obese people were r and omized into three groups and given 0 , 50 , or 100 mg of the opiate antagonist naltrexone for 8 weeks in an outpatient , double‐blind study . Weight loss was not significant in either the 50 or 100 mg groups as compared with placebo . However , when broken down by sex , women had a significant ( P < 0.05 ) weight loss of 1.7 kg , while men did not lose weight . Side effects were modest , but six subjects had one or more abnormal liver function test results ; in one subject these abnormalities appeared to be clinical ly significant . The effects of naltrexone on weight loss were less than expected in light of prior animal studies , but further studies with a wider dose range of naltrexone may be indicated CONTEXT The efficacy of current central ly acting obesity pharmacotherapies is limited by compensatory mechanisms that mitigate weight loss . OBJECTIVE Our objective was to determine whether opioid receptor antagonism ( naltrexone ) plus pro-opiomelanocortin activation ( bupropion ) causes greater weight loss than placebo or monotherapy . DESIGN / SETTING A r and omized , placebo- and monotherapy-controlled , double-blind , dose-finding trial was conducted from August 2005 to December 2006 in seven U.S. outpatient clinics . PARTICIPANTS A total of 419 patients with uncomplicated obesity participated . INTERVENTIONS Interventions included 24 wk of sustained-release bupropion ( 400 mg/d ) , immediate-release naltrexone ( 48 mg/d ) , placebo , and three combination therapy [ naltrexone/bupropion ( NB ) ] groups consisting of immediate-release naltrexone , 16 , 32 , or 48 mg/d , plus sustained-release bupropion ( 400 mg/d ) with a 24-wk extension . A minimal diet and exercise component was also included . MAIN OUTCOME MEASURES Percent weight change from baseline at wk 24 in the intent-to-treat population for NB48 vs. placebo and monotherapy was assessed . Other measurements included body mass index , waist circumference , fasting lipids , glycemic variables , safety , and tolerability . RESULTS At wk 24 , placebo-subtracted weight loss was -4.62 % [ 95 % confidence interval ( CI ) -6.24 to -2.99 ; P < 0.001 ] for NB16 , -4.65 % ( 95 % CI -6.20 to -3.09 ; P < 0.001 ) for NB32 , and -3.53 % ( 95 % CI -5.15 to -1.90 ; P < 0.001 ) for NB48 . Weight loss was statistically significant vs. monotherapy for all three NB combinations with the exception of NB48 vs. bupropion . Weight loss with NB continued after wk 24 . The most common treatment-emergent adverse event was mild transient nausea . CONCLUSIONS NB caused gradual sustained weight loss over 48 wk ; NB32 and NB16 demonstrated greater weight loss in the intent-to-treat population due to lower attrition rates . Further study is needed to demonstrate long-term efficacy and safety of NB OBJECTIVE On the basis of the clinical observations that bupropion facilitated weight loss , we investigated the efficacy and tolerability of this drug in overweight and obese adult women . RESEARCH METHODS AND PROCEDURES A total of 50 overweight and obese ( body mass index : 28.0 to 52.6 kg/m(2 ) ) women were included . The core component of the study was a r and omized , double-blind , placebo-controlled comparison for 8 weeks . Bupropion or placebo was started at 100 mg/d with gradual dose increase to a maximum of 200 mg twice daily . All subjects were prescribed a 1600 kcal/d balanced diet and compliance was monitored with food diaries . Responders continued the same treatment in a double-blind manner for an additional 16 weeks to a total of 24 weeks . There was additional single-blind follow-up treatment for a total of 2 years . RESULTS Subjects receiving bupropion achieved greater mean weight loss ( last-observation-carried-forward analysis ) over the first 8 weeks of the study ( p = 0.0001 ) : 4.9 % + /- 3.4 % ( n = 25 ) for bupropion treatment compared with 1.3 % + /- 2.4 % ( n = 25 ) for placebo treatment . For those who completed the 8 weeks , the comparison was 6.2 % + /- 3.1 % ( n = 18 ) vs. 1.6 % + /- 2.9 % ( n = 13 ) , respectively(p = 0.0002 ) , with 12 of 18 of the bupropion subjects ( 67 % ) losing over 5 % of baseline body weight compared with 2 of 13 in the placebo group ( 15 % ; p = 0.0094 ) . In the continuation phase , 14 bupropion responders who completed 24 weeks achieved weight loss of 12.9 % + /- 5.6 % with fat accounting for 73.5 % + /- 3.7 % of the weight lost and no change in bone mineral density as assessed by DXA . Bupropion was generally well-tolerated in this sample . DISCUSSION Bupropion was more effective than placebo in achieving weight loss at 8 weeks in overweight and obese adult women in this preliminary study . Initial responders to bupropion benefited further in the continuation phase |
12,860 | 21,624,574 | Meta-analyses showed no differences for cortisol awakening response and cortisol awakening response after administration of dexamethasone , cortisol in blood , and blood pressure . | BACKGROUND Burnout is a stress state characterized by symptoms of mental exhaustion and physical fatigue , detachment from work , and feelings of diminished competence .
Several biomarkers have been tested for association with burnout , but the results are conflicting .
AIM The objective of this review was to identify potential biomarkers for burnout . | Background : Plasma prolactin levels are sensitive to dopamine and serotonin function , and fatigue . Low cortisol , dopamine and /or serotonin may be involved in burnout and detachment . Methods : In this double-blind within-subject study , we treated 9 female burnout subjects and 9 controls with 35 mg cortisol and placebo orally . We measured state affect and plasma prolactin , oxytocin , cortisol and adrenocorticotropic hormone levels , and administered an attachment question naire . Results : The burnout subjects displayed an extreme distribution of basal prolactin levels , displaying higher or lower levels compared to the controls . The low prolactin burnouts had profoundly low attachment scores and tended to have low oxytocin levels . The high prolactin burnout subjects tended to show cortisol-induced decreased prolactin and fatigue , and increased vigor . Conclusion : Results are consistent with the hypothesis that burnout subjects are either characterized by low serotonergic function or by low dopaminergic function , and that the latter group benefits from cortisol replacement . These preliminary results suggest that differentiating between two syndromes may resolve inconsistencies in research on burnout , and be necessary for selecting the right treatment strategy Burnout is presumed to be the result of chronic stress , and chronic stress is known to affect the HPA-axis . To date , studies on HPA-axis functioning in burnout have showed inconsistent results . In the present study , a large sample ( n=74 ) of clinical ly diagnosed burnout individuals , mostly on sick-leave , were included and compared with 35 healthy controls . Salivary cortisol was sample d on 2 days to determine the cortisol awakening response ( CAR ) and the day-curve . In addition , the dexamethasone suppression test ( DST ) was applied to assess the feedback efficacy of the HPA-axis . There were no differences observed in the CAR , day-curve or CAR after DST in the burnout group as compared to a healthy control group . Burnout shows overlap in symptoms with chronic fatigue syndrome ( CFS ) and depression . Therefore , differential changes in HPA-axis functioning that resemble the hypo-functioning of the HPA-axis in CFS , or rather the hyper-functioning of the HPA-axis in depression , might have obscured the findings . However , no effect of fatigue or depressive mood on HPA-axis functioning was found in the burnout group . We concluded that HPA-axis functioning in clinical ly diagnosed burnout participants as tested in the present study , seems to be normal The authors prospect ively tested the hypothesis that obesity predicts burnout and the reverse-causation hypothesis that burnout predicts obesity . Respondents were 724 men and 340 women , apparently healthy employees , who underwent routine periodic health examinations at 2 points of time about 18 months apart . Obesity was assessed by body mass index , waist-hip ratio , and waist circumference . In regression analyses , done separately for men and women , the authors controlled for depressive symptomatology , sport activity , and Time 1 levels of the criterion . The hypothesis that burnout predicts obesity was not supported . The authors found that Time 1 measures of obesity predicted reductions rather than the hypothesized elevations of Time 2 burnout levels . The authors also found that for male respondents with relatively higher levels of Time 1 burnout , the higher their level of Time 1 obesity measure , the lower their level of T2 burnout The author ’ goal was to document baseline pituitaryadrenal hormonal and related metabolic variables in 16 female patients with burnout . Then , following stress management intervention , to compare the changes with an equal number of untreated control subjects . At monthly intervals for 4 mo , 24-h urine sample s were obtained for determination of free cortisol excretion . In addition , fasting blood sample s were analyzed for levels of cortisol , dehydroepi and rosterone sulfate ( DHEAS ) , ACTH , aldosterone , and catecholamines . Other biochemical measurements included growth hormone , prolactin , insulin , glucose , and lipid components . The Maslach Burnout Inventory , General Health Question naire-28 , and Zung depression rating scale were completed on each consecutive visit . The most striking finding was the reduction of urine free-cortisol excretion in the patients compared with controls . Initial urinary free cortisol was significantly lower in the patients ( mean ± SEM=47.2 ± 11.0 vs 79.0 ± 6.8 nmol/L , P=0.02 ) and remained significantly reduced at 4 mo ( mean ± SEM=44.0 ± 6.1 vs 91.1 ± 8.8 nmol/L , p=0.0001 ) . There were no significant changes in the other hormonal and biochemical data . We conclude that there is functional hypocortisolism in burnout , which is not immediately restored on stress management intervention despite clinical and psychological improvement Several studies have investigated the association between burnout and HPA-axis functioning , but the results are far from consistent . This does not preclude the possibility that within a group of burnout patients a recovery of symptoms in a longitudinal course corresponds to ( changes in ) cortisol parameters . The latter possibility is tested in the present study before and after treatment , and at follow-up . HPA-axis functioning and burnout complaints were assessed in burned-out participants at baseline ( n=74 ) , post-treatment ( n=62 ) and at follow-up ( n=53 ) . Multilevel regression analysis was used to test the hypothesis . Burnout complaints were significantly reduced at 8.5 months post-treatment , but there was no further reduction in complaints at follow-up 6.3 months later . Cortisol after awakening , and after dexamethasone intake showed no changes from baseline to post-treatment and follow-up . There was a small decline in cortisol during the day over the longitudinal course . The cortisol level after awakening in the longitudinal course showed significant positive association with the initial exhaustion level , a negative association with the change in the burnout exhaustion score , and a positive association with the change in depression . Although these associations are statistically significant , they only explain a small fraction of the variance in cortisol after awakening between and within persons . This implies that changes at symptom level are hardly related to changes in cortisol functioning , therefore the clinical implication s of this finding are limited Objective : This prospect i ve study was design ed to test the extent to which the onset of type 2 diabetes in apparently healthy individuals was predicted by burnout , a unique affective response to combined exposure to chronic stressors . Methods : The study participants were 677 employed men and women who were followed up for 3 to 5 years ( mean = 3.6 years ) for the onset of diagnosed type 2 diabetes . Burnout was assessed by the Shirom-Melamed Burnout Measure with its three subscales : emotional exhaustion , physical fatigue , and cognitive weariness . Results : The burnout symptoms were remarkably consistent over the follow-up period irrespective of changes in place of work and in employment status . During the follow-up period , 17 workers developed type 2 diabetes . Logistic regression results indicated that burnout was associated with a 1.84-fold increased risk of diabetes ( 95 % confidence interval [ CI ] = 1.19–2.85 ) even after adjusting for age , sex , body mass index , smoking , alcohol use , leisure time physical activity , initial job category , and follow-up duration . In a sub sample of 507 workers , the relative risk of diabetes was found to be much higher after additional control for blood pressure levels ( odds ratio = 4.32 , 95 % CI = 1.75–10.67 ) , available only for this sub sample . Conclusions : These findings suggest that chronic burnout might be a risk factor for the onset of type 2 diabetes in apparently healthy individuals . CI = confidence interval ; CVD = cardiovascular disease ; SMBM = Shirom-Melamed Burnout Measure ; HbA1c = glycosylated hemoglobin A1c ; VE = vital exhaustion ; MI = myocardial infa rct ion ; MBI = Maslach Burnout Inventory ; BMI = body mass index ; SBP = systolic blood pressure ; DBP = diastolic blood pressure ; OR = odds ratio ; APR = acute phase response ; CRP = C-reactive protein ; HDL = high-density lipoprotein ; HPA = hypothalamic – pituitary – adrenal OBJECTIVE To study the effects of occupational stress on immunological function , glucose , and blood lipid of female workers in oil-field . METHODS 900 female workers working in oil-field as observation group and 220 female not working in oil-field in 11 work types of oil industry in oil-field were selected as control group r and omly , occupational role , personal strain , and personal abilities of two groups were measured with occupational stress inventory-revised ( OSI-R ) . Then , 100 workers were selected r and omly from two groups Blood lipid , blood sugar , and immunological function were measured . RESULTS Occupational role and strain in observed group are significantly higher than control group ( P < 0.05 ) , However , there is no difference on personal abilities in two groups . Blood sugar , IgG , IgA , IgM , IL-6 content in observation group was significantly higher than control group , but CHO , HDL , LDL , IL-2 content was significantly less than control group ( P < 0.05 ) . TG content had no significant difference between both groups . There was positive correlation between occupational role , strain and , blood sugar , immunological function but negative correlation between personal abilities ( P < 0.05 ) . CONCLUSION The results show that blood sugar content was increased , CHO , HDL , LDL were decreased and immumological function was changed because of occupational stress . There was positive correlation between occupational role , strain and blood sugar , immunological function but negative correlation between personal re sources |
12,861 | 28,234,670 | For all other studies , the evidence across studies failed to reveal consistent effects on listening effort .
Conclusion : In summary , we could only identify scientific evidence from physiological measurement methods , suggesting that hearing impairment increases listening effort during speech perception ( Q1 ) .
There was no scientific , finding across studies indicating that hearing aid amplification decreases listening effort ( Q2 ) . | Objectives : To undertake a systematic review of available evidence on the effect of hearing impairment and hearing aid amplification on listening effort .
Two research questions were addressed : Q1 ) does hearing impairment affect listening effort ?
and Q2 ) can hearing aid amplification affect listening effort during speech comprehension ? | In this clinical study , 110 patients seen at three different clinical facilities were fit binaurally with linear , in-the-canal ( ITC ) hearing aids . All patients were new hearing aid users . Each of the hearing aids was equipped with an adjustable control that could be set by one of the audiologists ( Audiologist A ) at each site to convert it from a linear instrument to an experimental nonlinear one with automatic reduction of low-frquency gain at high input levels ( or base increase at low levels , BILL ) . Both the patient and the audiologist performing the outcome testing at each site ( Audiologist B ) were blind as to the present setting of the hearing aid . Each participant was enrolled in the study for a total of 12 weeks , with the hearing aid set to either the linear or BILL-processing mode of operation for the first 8 weeks and the opposite setting for a subsequent 4-week period . In summary , this was a prospect i ve , doubleblind , crossover study of 110 new hearing aid users . Outcome measures focused on hearing-aid benefit and included both objective and subjective measures . Objective measures were derived from scores on the Northwestern University Auditory Test NO . 6 ( NU-6 ) and the Connected Speech Test ( CST ) obtained for all possible combinations of two speech presentation levels ( 60 and 75 dB SPL ) two types of background noise ( cafeteria noise and multitalker babble ) , and two signal-to-noise ratios ( + 5 and + 10 dB ) . Subjective outcome measures included magnitude estimation of listening effort ( MELE ) , the abbreviated form of the Hearing Aid Performance Inventory ( HAPI ) , and estimations of hearing-aid usage based on daily-use logs kept by the participants . All of these measures were used to evaluate the benefit provided by linear amplification and the benefit result ing from the experimental BILL processing . Participant preferences for the experimental BILL-processing scheme or linear processing were also examined by using a paired-comparison task at the end of the study . Results were analyzed separately for three subgroups of patients ( mild , moderate , severe ) formed on the basis of their average hearing loss at 500 , 1000 , 2000 , and 4000 Hz . In all three subgroups , significant improvement in performance was observed for linear amplification and for BILL processing when compared to unaided performance . There were no significant differences in aided performance , however , between linear processing and the experimental BILL processing PURPOSE Using a dual-task paradigm , 2 experiments ( Experiments 1 and 2 ) were conducted to assess differences in the amount of listening effort expended to underst and speech in noise in audiovisual ( AV ) and audio-only ( A-only ) modalities . Experiment 1 had equivalent noise levels in both modalities , and Experiment 2 equated speech recognition performance levels by increasing the noise in the AV versus A-only modality . METHOD Sixty adults were r and omly assigned to Experiment 1 or Experiment 2 . Participants performed speech and tactile recognition tasks separately ( single task ) and concurrently ( dual task ) . The speech tasks were performed in both modalities . Accuracy and reaction time data were collected as well as ratings of perceived accuracy and effort . RESULTS In Experiment 1 , the AV modality speech recognition was rated as less effortful , and accuracy scores were higher than A only . In Experiment 2 , reaction times were slower , tactile task performance was poorer , and listening effort increased , in the AV versus the A-only modality . CONCLUSIONS At equivalent noise levels , speech recognition performance was enhanced and subjectively less effortful in the AV than A-only modality . At equivalent accuracy levels , the dual-task performance decrements ( for both tasks ) suggest that the noisier AV modality was more effortful than the A-only modality Cognitive task-evoked pupillary responses reliably index information-processing loads . However , previous studies have reported inconsistent findings regarding the nature of the pupillary response when processing dem and s approach or exceed available processing re sources . This condition was examined in 22 normal undergraduates by using pupillometric recordings during a digit span recall task , with 5 ( low load ) , 9 ( moderate load ) , and 13 ( excessive load ) digits per string . Pupillary responses increased systematic ally with increased processing load ( to-be-recalled digits ) until the limit of available re sources ( memory capacity of 7 + /- 2 digits ) , when they reached asymptote and then declined with re source overload ( > 9 digits ) . These findings suggest that pupillary responses increase systematic ally with increased processing dem and s that are below re source limits , change little during active processing at or near re source limits , and begin to decline when processing dem and s exceed available re sources Abstract Objective : Single channel noise reduction has been well investigated and seems to have reached its limits in terms of speech intelligibility improvement , however , the quality of such schemes can still be advanced . This study tests to what extent novel model-based processing schemes might improve performance in particular for non-stationary noise conditions . Design : Two prototype model-based algorithms , a speech-model-based , and a auditory-model-based algorithm were compared to a state-of-the-art non-parametric minimum statistics algorithm . A speech intelligibility test , preference rating , and listening effort scaling were performed . Additionally , three objective quality measures for the signal , background , and overall distortions were applied . For a better comparison of all algorithms , particular attention was given to the usage of the similar Wiener-based gain rule . Study sample : The perceptual investigation was performed with fourteen hearing-impaired subjects . Results : The results revealed that the non-parametric algorithm and the auditory model-based algorithm did not affect speech intelligibility , whereas the speech-model-based algorithm slightly decreased intelligibility . In terms of subjective quality , both model-based algorithms perform better than the unprocessed condition and the reference in particular for highly non-stationary noise environments . Conclusion : Data support the hypothesis that model-based algorithms are promising for improving performance in non-stationary noise conditions Speech recognition and cognitive functions important for speech underst and ing were evaluated by objective measures and by scores of perceived effort , with and without hearing aids . The tests were performed in silence , and with background conditions of speech spectrum r and om noise and ordinary speech . One young and one elderly group of twelve hearing-impaired subjects each participated . Hearing aid use improved speech recognition in silence ( 7 dB ) and in the condition with speech as background ( 2.5 dB S/N ) , but did not change the perceived effort scores . In the cognitive tests no hearing aid benefit was seen in objective measures , while there was an effect of hearing aid use in scores of perceived effort , subjects reported less effort . There were no age effects on hearing aid benefit . In conclusion , hearing aid use may result in reduced effort in listening tasks that is not associated with improvement in objective scores The purpose of this study was to determine the impact of a digital noise reduction ( DNR ) scheme implemented in a current commercial hearing aid . In a double-blinded design , three conditions of onset time ( 4 , 8 , 16 seconds ) were r and omly assigned to the 25 subjects , plus one condition wherein the noise-reduction feature was disengaged . Subsequently , a fifth trial/condition , wherein the subject had access to three memories in which the different onsets were programmed , was carried out . For each of the five conditions , the subjects had an at-home trial , prior to obtaining self-report measures . Laboratory measures of speech perception showed no effect of the DNR , with or without the provision of visual cues . Laboratory-based ratings of ease of listening showed DNR-on ( all onset times ) to be rated significantly better than DNR-off ; for ratings of listening comfort , the 4-second onset time was rated significantly lower ( poorer ) than the 8-second onset or the DNR-off condition ; for ratings of sound quality , DNR-on or -off had no differential effect . Self-report measures indicated significantly higher aversiveness in the DNR-off condition compared to the pre-test |
12,862 | 29,424,751 | The present study demonstrated that there is no significant relationship between TNFSF4 gene polymorphism and cerebrovascular and cardiovascular diseases | OBJECTIVE To evaluate the association between the tumor necrosis factor superfamily member 4 ( TNFSF4 ) gene polymorphisms and common cardiovascular and cerebrovascular diseases . | Tumor necrosis factor superfamily member 4 ( TNFSF4 ) plays a key role in the process of atherosclerosis , a common risk factor for both myocardial and cerebral infa rct ions . Recent studies indicate that the single nucleotide polymorphism ( SNP ) rs3850641 in TNFSF4 is associated with higher risk of myocardial infa rct ion , but little is known about the association between TNFSF4 variation and cerebral infa rct ion ( CI ) . A case-control study involving 385 CI patients and 385 age-matched , sex-matched non-CI controls was conducted in a Chinese population , only the most common subtype , atherosclerosis CI , was recruited . Two SNPs of TNFSF4 , rs3850641 and rs3861950 , were genotyped by the TaqMan SNP genotyping method , and verified partly by genomic DNA sequencing . The results revealed a significant allelic association between rs3861950 and CI ( Odds ration = 1.733 , 95 % confidence interval = 1.333–2.254 , P = 0.000 ) . Genotypic association analysis demonstrated that the CC genotype of rs3861950 confers susceptibility to CI ( Odds ration = 2.896 , 95 % confidence interval = 1.368–6.132 ) , and it was associated with a significantly higher risk of ischemic stroke ( Odds ration = 3.520 , 95 % confidence interval = 1.546–8.015 , P = 0.003 ) after adjusting for the other confirmed risk factors such as the history of hypertension , diabetes , CAD , smoking and alcohol drinking . While the odds ratio of the T allele to the C allele was 1.733 ( 95 % confidence interval : 1.333–2.254 ) . However , there was no significant association between rs3850641 and CI ( Odds ration = 1.288 , 95 % confidence interval = 0.993–1.670 , P = 0.056 ) . TNFSF4 gene polymorphism rs3861950 , but not rs3850641 , is associated with the risk of atherosclerosis CI in a Chinese population Background —CD4 T lymphocytes accumulate in unstable plaque . The direct and indirect involvement of these T cells in tissue injury and plaque instability is not understood . Methods and Results —Gene profiling identified perforin , CD161 , and members of the killer-cell immunoglobulin-like receptors as being differentially expressed in CD4+CD28null T cells , a T-cell subset that preferentially infiltrates unstable plaque . Frequencies of CD161 + and perforin-expressing CD4 T cells in peripheral blood were significantly increased in patients with unstable angina ( UA ) . CD161 appeared on CD4+CD28null T cells after stimulation , suggesting spontaneous activation of circulating CD4 T cells in UA . Perforin-expressing CD4 + T-cell clones from patients with UA exhibited cytotoxic activity against human umbilical vein endothelial cells ( HUVECs ) in redirected cytotoxicity assays after T-cell receptor triggering and also after stimulation of major histocompatibility complex class I – recognizing killer-cell immunoglobulin-like receptors . HUVEC cytolysis was dependent on granule exocytosis , as demonstrated by the paralyzing effect of pretreating CD4+CD28null T cells with strontium . Incubation of HUVECs with C-reactive protein ( CRP ) increased HUVEC lysis in a dose-dependent fashion . Conclusions —In patients with UA , CD4 T cells undergo a change in functional profile and acquire cytotoxic capability . Cytotoxic CD4 T cells effectively kill endothelial cells ; CRP sensitizes endothelial cells to the cytotoxic process . We propose that T-cell – mediated endothelial cell injury is a novel pathway of tissue damage that contributes to plaque destabilization . The sensitizing effect of CRP suggests synergy between dysregulated T-cell function and acute phase proteins in acute coronary syndromes BACKGROUND Recent data have implicated tumor necrosis factor ( lig and ) superfamily , member 4 ( TNFSF4 ) gene variation in myocardial infa rct ion in women ; however , no prospect i ve data are available on either incident arterial or venous disorders . METHODS We evaluated 2 previously characterized TNFSF4 gene variants ( -921C > T and dbSNP rs3850641 ) with a ) incident arterial events using a prospect i ve case-cohort design with 344 incident CVD cases and 2254 control participants , all white , drawn from the Women 's Health Study cohort with 10 years of follow-up , and b ) venous thromboembolism ( VTE ) risk using a nested , matched case-control design of 108 white male pairs ( drawn from the Physicians ' Health Study cohort ) and a case-cohort design of white female participants consisting of 125 cases and 2269 controls ( drawn from the Women 's Health Study cohort ) , analyzed separately . RESULTS Genotype distributions were in Hardy-Weinberg equilibrium . Results from a marker-by-marker regression analysis , adjusting for traditional risk factors , showed a significant association of -921C > T with an increased risk of VTE in women ( additive : odds ratio 1.86 ; 95 % CI 1.17 - 2.92 , P = 0.008 ) in women . Furthermore , using a haplotype-based regression analysis , haplotype C-G was associated with a reduced risk of VTE relative to the referent haplotype , C-A ( odds ratio 0.50 ; 95 % CI 0.27 - 0.92 ; P = 0.02 ) . In contrast , we found little evidence for an association of the variants/haplotypes with risk of VTE in men or CVD risk in women ( as previously reported ) . CONCLUSIONS Our present findings , if corroborated in other prospect i ve investigations , suggest that the TNFSF4 variants tested may be useful indicators for assessing the risk of venous thromboembolism We recently showed that genetic variants in OX40L are associated with myocardial infa rct ion ( MI ) and severity of coronary artery disease in human . A number of studies also suggest a possible role for OX40 ( the OX40L receptor ) as a factor contributing to atherosclerosis . In the present study , the OX40 gene was screened for variants associated with precocious MI , using individuals with MI before the age of 60 and controls . Despite the fact that the OX40 gene is highly conserved between species and that relatively few common genetic variants were encountered , an association with MI was seen for a polymorphism in intron 5 ( rs2298212 ) . In silico investigation suggested that genetic variation ( rs2298211 ) , linked to this intronic variant , is possibly affecting spliceosome function . Our results provide evidence that variants in human OX40 might influence susceptibility to MI . The relevance of these findings is supported by the vital functions fulfilled by OX40 in mammals as reflected by the high level of evolutionary conservation |
12,863 | 27,377,922 | Conclusions In conclusion , the effectiveness and indication of pazopanib for use in the second-line setting has not yet been examined in-depth ; however , this meta- analysis has shown that the treatment effects in terms of PRR , DCR , and PFS may be similar to other well-studied second-line targeted therapies . | Background The currently recommended treatment algorithm for patients with advanced renal cell carcinoma who fail the first-line targeted therapy does not normally include pazopanib as a second-line treatment option .
It would therefore be of interest to determine the efficiency of pazopanib in this setting in terms of the partial response rate ( PRR ) , disease control rate ( DCR ) , and progression-free survival ( PFS ) . | BACKGROUND This phase II trial examined the activity and toxicity of second-line treatment with pazopanib after failure of first-line single-agent treatment with sunitinib or bevacizumab in patients with advanced clear cell renal carcinoma . PATIENTS AND METHODS Fifty-five patients with metastatic clear cell renal carcinoma who had previously received first-line treatment with sunitinib ( 39 patients ) or bevacizumab ( 16 patients ) were enrolled . Patients received pazopanib 800 mg orally daily and were evaluated for response after 8 weeks of treatment . Responses were measured using Response Evaluation Criteria in Solid Tumors ( RECIST ) , version 1.0 , and confirmed with repeated scans after 8 weeks . Patients with objective response or stable disease continued treatment until disease progression or unacceptable toxicity occurred . RESULTS Fifteen of 55 patients ( 27 % ) had objective response to pazopanib . An additional 27 patients ( 49 % ) had stable disease , for a disease control rate of 76 % . After a median follow-up of 16.7 months , the median progression-free survival for the entire group was 7.5 months ( 95 % confidence interval , 5.4 - 9.4 months ) . Similar progression-free survival was observed regardless of whether previous treatment was with sunitinib or bevacizumab . The estimated overall survival rate for the entire group at 24 months was 43 % . CONCLUSION Pazopanib is an active agent for the treatment of advanced clear cell renal carcinoma , even after failure of sunitinib or bevacizumab . Treatment with pazopanib should be considered early in the sequence of therapy for patients with advanced renal cell carcinoma BACKGROUND In a phase 3 trial comparing the efficacy and safety of axitinib versus sorafenib as second-line treatment for metastatic renal cell carcinoma , patients given axitinib had a longer progression-free survival ( PFS ) . Here , we report overall survival and up date d efficacy , quality of life , and safety results . METHODS Eligible patients had clear cell metastatic renal cell carcinoma , progressive disease after one approved systemic treatment , and an Eastern Cooperative Oncology Group performance status ( ECOG PS ) of 0 - 1 . 723 patients were stratified by ECOG PS and previous treatment and r and omly allocated ( 1:1 ) to receive axitinib ( 5 mg twice daily ; n=361 ) or sorafenib ( 400 mg twice daily ; n=362 ) . The primary endpoint was PFS assessed by a masked , independent radiology review committee . We assessed patient-reported outcomes using vali date d question naires . Baseline characteristics and development of hypertension on treatment were studied as prognostic factors . Efficacy was assessed in the intention-to-treat population , and safety was assessed in patients who received at least one dose of the study drug . This ongoing trial is registered on Clinical Trials.gov , number NCT00678392 . FINDINGS Median overall survival was 20.1 months ( 95 % CI 16.7 - 23.4 ) with axitinib and 19.2 months ( 17.5 - 22.3 ) with sorafenib ( hazard ratio [ HR ] 0.969 , 95 % CI 0.800 - 1.174 ; one-sided p=0.3744 ) . Median investigator-assessed PFS was 8.3 months ( 95 % CI 6.7 - 9.2 ) with axitinib and 5·7 months ( 4.7 - 6.5 ) with sorafenib ( HR 0.656 , 95 % CI 0.552 - 0.779 ; one-sided p<0.0001 ) . Patient-reported outcomes scores were similar in the treatment groups at baseline , were maintained during treatment , but decreased at end-of-treatment . Common grade 3 or higher treatment-related adverse events were hypertension ( 60 [ 17 % ] ) , diarrhoea ( 40 [ 11 % ] ) , and fatigue ( 37 [ 10 % ] ) in 359 axitinib-treated patients and h and -foot syndrome ( 61 [ 17 % ] ) , hypertension ( 43 [ 12 % ] ) , and diarrhoea ( 27 [ 8 % ] ) in 355 sorafenib-treated patients . In a post-hoc 12-week l and mark analysis , median overall survival was longer in patients with a diastolic blood pressure of 90 mm Hg or greater than in those with a diastolic blood pressure of less than 90 mm Hg : 20.7 months ( 95 % CI 18.4 - 24.6 ) versus 12.9 months ( 10.1 - 20.4 ) in the axitinib group ( p=0.0116 ) , and 20.2 months ( 17.1 - 32.0 ) versus 14.8 months ( 12.0 - 17.7 ) in the sorafenib group ( one-sided p=0.0020 ) . INTERPRETATION Although overall survival , a secondary endpoint for the study , did not differ between the two groups , investigator-assessed PFS remained longer in the axitinib group compared with the sorafenib group . These results establish axitinib as a second-line treatment option for patients with metastatic renal cell carcinoma . FUNDING Pfizer |
12,864 | 28,133,489 | Aromatherapy showed potential to be used as an effective therapeutic option for the relief of depressive symptoms in a wide variety of subjects .
Particularly , aromatherapy massage showed to have more beneficial effects than inhalation aromatherapy | Background .
Depression is one of the greatest health concerns affecting 350 million people globally .
Aromatherapy is a popular CAM intervention chosen by people with depression .
Due to the growing popularity of aromatherapy for alleviating depressive symptoms , in-depth evaluation of the evidence -based clinical efficacy of aromatherapy is urgently needed .
This systematic review aims to provide an analysis of the clinical evidence on the efficacy of aromatherapy for depressive symptoms on any type of patients . | BACKGROUND Menopausal symptoms experienced by women vary widely , and while many women transition through menopause with manageable symptoms , others experience severe symptoms , which may impair their quality of life . OBJECTIVES A r and omized clinical trial was conducted to determine the effect of aromatherapy massage on psychological symptoms during menopause . METHODS The study population comprised 90 women . Each subject in the aromatherapy massage group received 30 min aromatherapy sessions with aroma oil , twice a week , for four weeks ; each subject in the massage therapy group received the same treatment with odorless oil , while no treatment was provided to subjects in the control group . The outcome measures were psychological symptoms , as obtained through the psychological subscale of the Menopause Rating Scale . RESULTS A total of 87 women were evaluated . A statistically significant difference was found between the participants ' pre- and post-application psychological score in intervention groups , whereas the score in the control group did not differ significantly . Aromatherapy massage decreased the psychological score MD : -3.49 ( 95 % Confidence Interval of Difference : -4.52 to -2.47 ) . Massage therapy also decreased the psychological score MD : -1.20 ( 95 % Confidence Interval of Difference : -2.19 to -0.08 ) . To distinguish the effect of aromatherapy from massage separately , we compared the reduction in the psychological score . Aromatherapy massage decreased the psychological score more than massage therapy MD : -2.29 ( 95 % Confidence Interval of Difference : -3.01 to -0.47 ) . CONCLUSION Both aromatherapy massage and massage were effective in reducing psychological symptoms , but , the effect of aromatherapy massage was higher than massage The existing review s of massage therapy ( MT ) research are either limited to infants , adults , or were conducted prior to the publication of the most recent studies using pediatric sample s. R and omized controlled trials ( RCTs ) of pediatric MT are review ed . A literature search yielded 24 RCTs of pediatric MT , defined as the manual manipulation of soft tissue intended to promote health and well-being in recipients between 2 and 19 years of age . Because RCTs of pediatric MT varied considerably in the amount and types of data reported , quantitative and narrative review methods were both used . Singledose and multiple-dose effects were examined separately . Among single-dose effects , significant reductions of state anxiety were observed at the first session ( g 1⁄4 0.59 , P < 0.05 ) and the last session ( g 1⁄4 1.10 , P < 0.01 ) of a course of treatment . Effects for salivary cortisol ( g 1⁄4 0.28 ) , negative mood ( g 1⁄4 0.52 ) and behavior ( g 1⁄4 0.37 ) were non-significant . Three of eleven multiple-dose effects were statistically significant . These were trait anxiety ( g 1⁄4 0.94 , P < 0.05 ) , muscle tone ( g 1⁄4 0.90 , P < 0.01 ) and arthritis pain ( g1⁄4 1.33 , P < 0.01 ) . Results of studies not permitting effect size calculation were judged to be generally consistent with quantitative results . MT benefits pediatric recipients , though not as universally as sometimes reported . Numerous weaknesses endemic to MT research ( e.g. low statistical power , frequent failure to report basic descriptive statistics ) are identified , and recommendations for future pediatric MT research are discussed Research suggests that patients with cancer , particularly in the palliative care setting , are increasingly using aromatherapy and massage . There is good evidence that these therapies may be helpful for anxiety reduction for short periods , but few studies have looked at the longer term effects . This study was design ed to compare the effects of four-week courses of aromatherapy massage and massage alone on physical and psychological symptoms in patients with advanced cancer . Forty-two patients were r and omly allocated to receive weekly massages with lavender essential oil and an inert carrier oil ( aromatherapy group ) , an inert carrier oil only ( massage group ) or no intervention . Outcome measures included a Visual Analogue Scale ( VAS ) of pain intensity , the Verran and Snyder-Halpern ( VSH ) sleep scale , the Hospital Anxiety and Depression ( HAD ) scale and the Rotterdam Symptom Checklist ( RSCL ) . We were unable to demonstrate any significant long-term benefits of aromatherapy or massage in terms of improving pain control , anxiety or quality of life . However , sleep scores improved significantly in both the massage and the combined massage ( aromatherapy and massage ) groups . There were also statistically significant reductions in depression scores in the massage group . In this study of patients with advanced cancer , the addition of lavender essential oil did not appear to increase the beneficial effects of massage . Our results do suggest , however , that patients with high levels of psychological distress respond best to these therapies OBJECTIVE This study investigated the soothing effects of fragrance from yuzu , a Japanese citrus fruit ( Citrus junos Sieb . ex Tanaka ) , with salivary chromogranin A ( CgA ) used as an endocrinologic stress marker reflecting sympathetic nervous system activity . METHODS Twenty healthy women ( mean age , 20.5 ± 0.1 years ) participated in a r and omized , controlled , crossover study . Participants were examined on two separate occasions-once using the yuzu scent and once using unscented water as a control-in the follicular phase . This experiment measured salivary CgA and the Profile of Mood States ( POMS ) as a psychological index before and after the aromatic stimulation . RESULTS Ten-minute inhalation of the yuzu scent significantly decreased salivary CgA. At 30 minutes after the inhalation period , the salivary CgA level further decreased . In addition , POMS revealed that inhalation of the aromatic yuzu oil significantly decreased total mood disturbance , a global measure of affective state , as well as four subscores of emotional symptoms ( tension-anxiety , depression-dejection , anger-hostility , and confusion ) , as long as 30 minutes after the olfactory stimulation . CONCLUSIONS Yuzu 's aromatic effects may alleviate negative emotional stress , which , at least in part , would contribute to the suppression of sympathetic nervous system activity Background The Hamilton Depression Rating Scale ( HAM-D ) and the Montgomery – Asberg Depression Scale ( MADRS ) are used worldwide and considered st and ard scales for evaluating depressive symptoms . This paper aims to investigate the psychometric proprieties ( reliability and validity ) of these scales in a Brazilian sample , and to compare responses in bipolar and unipolar patients . Methods The sample comprised 91 patients with either bipolar I or major depressive disorder from a psychiatric institute at São Paulo , Brazil . Participants were recruited and treated by clinicians through the Structured Interview for DSM-IV criteria , and had previously been interviewed by a trained , blind tester . Results Both scales indicated good reliability properties ; however , the MADRS reliability statistics were higher than those of the HAM-D for detecting initial symptoms of unipolar depression . Correlation between the tests was moderate . Despite demonstrating adequate validity , neither test achieved the levels of sensitivity and specificity required for identification of a cutoff score to differentiate bipolar I and unipolar patients . Conclusions Both scales demonstrate adequate reliability and validity for assessing depressive symptoms in the Brazilian sample , and are good options to complement psychiatric diagnosis , but are not appropriate for distinguishing between the two affective disorder types Background Yuzu ( Citrus junos Sieb . ex Tanaka ) , a yellow-golden colored citrus fruit , has traditionally been used to promote psychosomatic health in Japan . While the yuzu produces a distinctive , pleasing aroma of citrus and floral , the efficacy of its fragrance remains unknown . The present study investigated the soothing effects of the fragrance of yuzu essential oil from the perspective of autonomic nervous system activity , which plays a crucial role in the integrity of the mind-body connection . Methods Twenty one women in their 20s participated in a single-blind r and omized controlled crossover study . Subjects were examined twice each in the follicular and late-luteal phases . Two kinds of aromatic stimulation ( yuzu and water as a control ) were used . This experiment measured heart rate variability ( HRV ) reflecting autonomic nervous system activity and used the Profile of Mood States ( POMS ) as a psychological index before and after the aromatic stimulation . Results Only a 10-min inhalation of the yuzu scent significantly decreased heart rate and increased high frequency power of HRV reflecting parasympathetic nervous system activity , regardless of menstrual phase . This significant physiological effect continued for at least 25 min . In addition , the POMS tests revealed that inhalation of the aromatic yuzu oil significantly decreased total mood disturbance , a global measure of affective state , together with two POMS subscales — tension-anxiety and fatigue , as long as 35 min after the aroma stimulation , both in the symptomatic late-luteal and non-symptomatic follicular phases . Conclusions The present study provides the novel information that yuzu ’s aromatic effects could serve to alleviate negative emotional stress , which , at least in part , would contribute to the improvement of parasympathetic nervous system activity OBJECTIVES The aim of this study was to determine if aromatherapy improves anxiety and /or depression in the high risk postpartum woman and to provide a complementary therapy tool for healthcare practitioners . DESIGN The pilot study was observational with repeated measures . SETTING Private consultation room in a Women 's center of a large Indianapolis hospital . SUBJECTS 28 women , 0 - 18 months postpartum . INTERVENTIONS The treatment groups were r and omized to either the inhalation group or the aromatherapy h and m'technique . Treatment consisted of 15 min sessions , twice a week for four consecutive weeks . An essential oil blend of rose otto and lav and ula angustifolia @ 2 % dilution was used in all treatments . The non-r and omized control group , comprised of volunteers , was instructed to avoid aromatherapy use during the 4 week study period . Allopathic medical treatment continued for all participants . OUTCOME MEASUREMENTS All subjects completed the Edinburgh Postnatal Depression Scale ( EPDS ) and Generalized Anxiety Disorder Scale ( GAD-7 ) at the beginning of the study . The scales were then repeated at the midway point ( two weeks ) , and at the end of all treatments ( four weeks ) . RESULTS Analysis of Variance ( ANOVA ) was utilized to determine differences in EPDS and /or GAD-7 scores between the aromatherapy and control groups at baseline , midpoint and end of study . No significant differences were found between aromatherapy and control groups at baseline . The midpoint and final scores indicated that aromatherapy had significant improvements greater than the control group on both EPDS and GAD-7 scores . There were no adverse effects reported . CONCLUSION The pilot study indicates positive findings with minimal risk for the use of aromatherapy as a complementary therapy in both anxiety and depression scales with the postpartum woman . Future large scale research in aromatherapy with this population is recommended UNLABELLED Distress associated with cancer often presents with symptoms of depression and /or anxiety . Cognitive Behaviour Therapy ( CBT ) is one of the most effective psychological treatments . Complementary therapies , especially aromatherapy massage ( AM ) , are also popular and alleviate anxiety . No studies have directly compared these two treatments . AIMS The aim of this study is to ( 1 ) test the feasibility of recruitment into a r and omised controlled trial of AM versus CBT in patients with cancer ; ( 2 ) test and modify the intervention ; ( 3 ) determine whether changes in outcomes were consistent with published data . METHODS Patients at all stages of cancer , recruited from oncology outpatient clinics and screening eight or more for anxiety and /or depression on the HADS , were r and omised to Treatment as Usual ( TAU ) plus up to eight sessions weekly of either AM or CBT , offered within 3 months . The POMS was collected at baseline and 3 and 6 months post baseline . RESULTS Of those suitable , over 60 % ( 39/63 ) participated ( AM , n = 20 ; CBT , n = 19 ) and over 90 % ( 36/39 ) were followed up . Both packages were well received . The preference was for AM , with more sessions were taken up ; ( Mean number sessions AM = 7.2 ( SD 2.0 ) and CBT = 5.4 ( SD 3.1 ) ; P<0.05 ) . Significant improvements in POMS ( Total Mood , depression and anxiety scores ) occurred with both interventions . Between-group comparison showed a non-significant trend towards greater improvement in depression with CBT . CONCLUSIONS Recruitment was feasible ; the interventions acceptable and engagement with treatment was high . Improvements with both interventions were observed . The beneficial effects on depression with CBT appeared to be sustained OBJECTIVES Stress reduction care is important for pregnant women to decrease obstetric complications and children 's health problems after birth . The aim of this study is to clarify the physical and psychologic effects of inhalation aromatherapy on pregnant women . Essential oils with high linalool and linalyl acetate content that may be used during pregnancy were selected and among these , and the one preferred by the participant was used . DESIGN This was a prospect i ve , r and omized , controlled trial . SETTING S/LOCATION This trial was performed at a gynecology outpatient department in a hospital in Kyoto , Japan . PARTICIPANTS The study included pregnant women in week 28 of a single pregnancy with a normal course . INTERVENTIONS Participants were r and omly assigned into an aromatherapy group and a control group . They were seated in the resting , seated position for 10 minutes . During the latter 5 minutes of each 10-minute session , aromatherapy inhalation was performed for the aromatherapy group . OUTCOME MEASURES Before and after the intervention , the Profile of Mood States ( POMS ) was measured . During the trial , the heart-rate fluctuations were measured for the autonomic nervous system regulation . RESULTS A total of 13 pregnant women participated in the trial . Seven ( 7 ) participants were assigned to the aromatherapy group and 6 participants to the control group . The results of the POMS were such that based on an intragroup comparison , significant differences were observed in the Tension-Anxiety score ( p<0.05 ) and the Anger-Hostility score ( p<0.05 ) , and the respective improvements observed were due to aromatherapy . The results of the autonomic nervous system regulation were such that based on an intragroup comparison within the aromatherapy group , the parasympathetic nerve activity increased significantly ( p<0.05 ) . CONCLUSIONS Aromatherapy inhalation using essential oils containing linalyl acetate and linalool was found to be effective for the POMS and parasympathetic nerve activity , based on an intragroup comparison . However , based on a comparison between the groups , no substantial difference was observed ; hence , further study is necessary in the future PURPOSE To test the effectiveness of supplementing usual supportive care with aromatherapy massage in the management of anxiety and depression in cancer patients through a pragmatic two-arm r and omized controlled trial in four United Kingdom cancer centers and a hospice . PATIENTS AND METHODS Two hundred eighty-eight cancer patients , referred to complementary therapy services with clinical anxiety and /or depression , were allocated r and omly to a course of aromatherapy massage or usual supportive care alone . RESULTS Patients who received aromatherapy massage had no significant improvement in clinical anxiety and /or depression compared with those receiving usual care at 10 weeks postr and omization ( odds ratio [ OR ] , 1.3 ; 95 % CI , 0.9 to 1.7 ; P = .1 ) , but did at 6 weeks postr and omization ( OR , 1.4 ; 95 % CI , 1.1 to 1.9 ; P = .01 ) . Patients receiving aromatherapy massage also described greater improvement in self-reported anxiety at both 6 and 10 weeks postr and omization ( OR , 3.4 ; 95 % CI , 0.2 to 6.7 ; P = .04 and OR , 3.4 ; 95 % CI , 0.2 to 6.6 ; P = .04 ) , respectively . CONCLUSION Aromatherapy massage does not appear to confer benefit on cancer patients ' anxiety and /or depression in the long-term , but is associated with clinical ly important benefit up to 2 weeks after the intervention The purpose of this study was to assess the effects of water , lavender , or rosemary scent on physiology and mood state following an anxiety-provoking task . The nonsmoking participants , ages 18–30 years , included 42 women and 31 men who reported demographic information and measures of external temperature and heart rate were taken prior to introduction of an anxiety-eliciting task and exposure to lavender , rosemary , or water scents . Following the task , participants completed the Profile of Mood States to assess mood , and temperature and heart rate were reassessed . Participants rated the pleasantness of the scent received . When pleasantness ratings of scent were covaried , physiological changes in temperature and heart rate did not differ based on scent exposure , but mood ratings differed by scent condition . Participants in the rosemary condition scored higher on measures of tension – anxiety and confusion – bewilderment relative to the lavender and control conditions . The lavender and control conditions showed higher mean vigor – activity ratings relative to the rosemary group , while both rosemary and lavender scents were associated with lower mean ratings on the fatigue – inertia subscale , relative to the control group . These results suggest that , when individual perception of scent pleasantness is controlled , scent has the potential to moderate different aspects of mood following an anxiety-provoking task OBJECTIVES Idiopathic Environmental Intolerance ( IEI ) is an acquired disorder with multiple recurrent symptoms , which is associated with diverse environmental factors that are tolerated by the majority of people . IEI is an illness of uncertain aetiology , making it difficult to treat using conventional medicine . Therefore , there is a need for novel therapies to control the symptoms of IEI . The objective of this study was to evaluate the feasibility and impact of aromatherapy massage for individuals with IEI . DESIGN Non-blinded crossover trial . SETTING IEI patients who attended a clinic in Sapporo city were recruited , and sixteen patients were enrolled . Participants were clinical ly examined by an experienced medical doctor and met the criteria included in the working definition of IEI disorder . INTERVENTIONS During the active period , participants received four one-hour aromatherapy massage sessions every two weeks . During the control period , the participants did not receive any massages . MAIN OUTCOME MEASUREMENTS Scores on the IEI-scales trigger checklist , symptoms , life impact , and the State Anxiety Inventory were assessed before and after each period . Short-term mood enhancement was evaluated using the Profiles of Mood Status ( POMS ) before and after sessions . RESULTS Due to period effects , evaluation of the results had to be restricted to the first period , and the result showed no effect of intervention . All six sub-scales of the POMS improved after each session ( mean score differences : 4.89 - 1.33 , P<0.05 ) . CONCLUSIONS Aromatherapy was well tolerated by subjects with IEI ; however , aromatherapy , as applied in this study , did not suggest any specific effects on IEI condition The use of complementary therapies , such as massage and aromatherapy massage , is rising in popularity among patients and healthcare professionals . They are increasingly being used to improve the quality of life of patients , but there is little evidence of their efficacy . This study assessed the effects of massage and aromatherapy massage on cancer patients in a palliative care setting . We studied 103 patients , who were r and omly allocated to receive massage using a carrier oil ( massage ) or massage using a carrier oil plus the Roman chamomile essential oil ( aromatherapy massage ) . Outcome measurements included the Rotterdam Symptom Checklist ( RSCL ) , the State – Trait Anxiety Inventory ( STAI ) and a semi-structured question naire , administered 2 weeks postmassage , to explore patients ' perceptions of massage . There was a statistically significant reduction in anxiety after each massage on the STAI ( P < 0.001 ) , and improved scores on the RSCL : psychological ( P < 0.001 ) , quality of life ( P < 0.01 ) , severe physical ( P < 0.05 ) , and severe psychological ( P < 0.05 ) subscales for the combined aromatherapy and massage group . The aromatherapy group 's scores improved on all RSCL subscales at the 1 % level of significance or better , except for severely restricted activities . The massage group 's scores improved on four RSCL subscales but these improvements did not reach statistical significance . Massage with or without essential oils appears to reduce levels of anxiety . The addition of an essential oil seems to enhance the effect of massage and to improve physical and psychological symptoms , as well as overall quality of life OBJECTIVES Aromatherapy massage is commonly used for the stress management of healthy individuals , and also has been often employed as a therapeutic use for pain control and alleviating psychological distress , such as anxiety and depression , in oncological palliative care patients . However , the exact biological basis of aromatherapy massage is poorly understood . Therefore , we evaluated here the effects of aromatherapy massage interventions on multiple neurobiological indices such as quantitative psychological assessment s , electroencephalogram ( EEG ) power spectrum pattern , salivary cortisol and plasma brain-derived neurotrophic factor ( BDNF ) levels . DESIGN A control group without treatment ( n = 12 ) and aromatherapy massage group ( n = 13 ) were r and omly recruited . They were all females whose children were diagnosed as attention deficit hyperactivity disorder and followed up in the Department of Psychiatry , Jeju National University Hospital . Participants were treated with aromatherapy massage for 40 min twice per week for 4 weeks ( 8 interventions ) . RESULTS A 4-week-aromatherapy massage program significantly improved all psychological assessment scores in the Stat-Trait Anxiety Index , Beck Depression Inventory and Short Form of Psychosocial Well-being Index . Interestingly , plasma BDNF levels were significantly increased after a 4 week-aromatherapy massage program . Alpha-brain wave activities were significantly enhanced and delta wave activities were markedly reduced following the one-time aromatherapy massage treatment , as shown in the meditation and neurofeedback training . In addition , salivary cortisol levels were significantly reduced following the one-time aromatherapy massage treatment . CONCLUSIONS These results suggest that aromatherapy massage could exert significant influences on multiple neurobiological indices such as EEG pattern , salivary cortisol and plasma BDNF levels as well as psychological assessment OBJECTIVE Though often lifesaving , stem cell transplantation ( SCT ) is a period of great distress for both child and parent . METHODS We conducted a double-blind , placebo-controlled r and omized study evaluating the effect of the respiratory administration of bergamot essential oil on the anxiety , nausea , and pain of 37 pediatric patients with malignant and non-malignant disorders undergoing stem cell infusion and their parents . Patients were assessed at the time of recruitment , prior to infusion , upon infusion completion , and one hour post-infusion using the Spielberger State-Trait Anxiety Inventory ( STAI ) for parents and the STAIC , Children 's Behavioral Style Scale ( CBSS ) , visual analogue scale ( VAS ) for pain and nausea , and the Emotionality Activity Sociability and Impulsivity instrument ( EASI ) for children . RESULTS Children and adolescents in the treatment group experienced greater anxiety ( p = 0.05 ) and nausea ( p = 0.03 ) one hour post-infusion . Reported pain in both groups was no longer significant one hour post-infusion . Parental anxiety declined in both groups but did not reach statistical significance . Child 's monitoring coping style was significantly predictive of transitory anxiety post-infusion ( p = 0.01 ) . CONCLUSIONS Although this trial did not report a benefit of inhalation aromatherapy for reducing anxiety , nausea , or pain when added to st and ard supportive care , it provides the first experimental rather than descriptive report on testing a single therapeutic essential oil among children and adolescents undergoing stem cell infusion . Future research may consider exploring the cutaneous application of essential oil through massage or other psychoeducational counseling interventions among parents with elevated anxiety and patients with greater information seeking coping styles during SCT Depressive disorders are a major health care issue and one of the foremost causes of disability in adults around the world , result ing in significant costs to society and health care systems ( 1 ) . The estimated economic burden associated with depression was $ 83.1 billion in 2000 and is probably higher today ( 2 ) . Depressive disorders include major depressive disorder ( MDD ) ; dysthymia ; and subsyndromal depression , including minor depression . Major depressive disorder is the most prevalent depressive disorder , with an estimated lifetime prevalence of 16 % in the United States ( 3 ) . An average of 8 million ambulatory care visits per year result in a primary diagnosis of MDD ( 4 ) . The American Psychiatric Association ( 5 ) defines MDD as depressed mood or loss of pleasure or interest along with other symptoms , including significant change in weight or appetite , insomnia or hypersomnia , psychomotor agitation or retardation nearly every day , fatigue or loss of energy , feelings of worthlessness or excessive or inappropriate guilt , indecisiveness or decreased ability to concentrate , and recurrent thoughts of death or suicide , that last for at least 2 weeks and affect normal functioning . Dysthymia is less severe , but symptoms last for 2 or more years . In contrast , subsyndromal depression is associated with less severe symptoms of depression that do not qualify for MDD or dysthymia diagnoses . The treatment of depression can be characterized by 3 phases ( Figure 1 ) : acute ( 6 to 12 weeks ) , continuation ( 4 to 9 months ) , and maintenance ( 1 year ) ( 7 ) . Relapse is defined as the return of depressive symptoms during the acute or continuation phases and is therefore considered part of the same depressive episode , whereas recurrence is defined as the return of depressive symptoms during the maintenance phase and is considered a new , distinct episode . Response to treatment ( typically defined as 50 % reduction in measured severity ) can be quantified using various tools , such as the Patient Health Question naire-9 ( PHQ-9 ) ( 7 ) or the Hamilton Depression Rating Scale ( HAM-D ) ( 8) . Figure 1 . Phases of treatment of major depression . Adapted from reference 6 . TX = treatment . Various treatment approaches can be used to manage MDD , such as psychotherapy , complementary and alternative medicine ( CAM ) , exercise , and pharmacotherapy . The psychological interventions used to treat depression include acceptance and commitment therapy , cognitive therapy , cognitive behavioral therapy ( CBT ) , interpersonal therapy , and psychodynamic therapies ( Table 1 ) . The CAM treatments include acupuncture , meditation , -3 fatty acids , S-adenosyl-l-methionine ( SAMe ) , St. John 's wort , and yoga . Exercise includes a broad range of activities that can be done for varying duration s , in classes , individually , or in informal groups . For pharmacologic therapy , the scope of this guideline is limited to second-generation antidepressants ( SGAs ) ( selective serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , and selective serotonin norepinephrine reuptake inhibitors ) . First-generation antidepressants ( tricyclic antidepressants and monoamine oxidase inhibitors ) are very rarely used because SGAs have lower toxicity in overdose than first-generation antidepressants and similar efficacy . Table 1 . Common Psychological Interventions to Treat Depression Guideline Focus and Target Population The purpose of this guideline from the American College of Physicians ( ACP ) is to summarize and grade the evidence on the comparative effectiveness and safety of nonpharmacologic treatments and SGAs ( including serotonin reuptake inhibitors , serotonin norepinephrine reuptake inhibitors , bupropion , mirtazapine , nefazodone , and trazodone ) , alone or in combination , for MDD . The target audience for this guideline includes all clinicians , and the target patient population includes all adults with MDD . These recommendations are based on a background evidence article ( 9 ) and a systematic evidence review sponsored by the Agency for Healthcare Research and Quality ( AHRQ ) ( 6 ) . Methods Systematic Review of the Evidence The systematic evidence review was conducted by the AHRQ 's RTI InternationalUniversity of North Carolina at Chapel Hill Evidence -based Practice Center ( 6 ) . Additional method ological details can be found in the Appendix ) , accompanying background evidence article ( 9 ) , and full report ( 6 ) . Review ers search ed several data bases for studies published in English , German , or Italian from 1 January 1990 through September 2015 . Studies on efficacy were limited to r and omized , controlled trials and systematic review s and meta-analyses , although evidence on harms included observational studies . Review ers combined data when possible using meta- analysis and assessed the risk of bias and quality of studies according to established methods . The study population included adult out patients ( aged 18 years ) with MDD during either an initial or a second treatment attempt who did not remit after an initial adequate trial with an SGA . The review evaluated the following classes of interventions : depression-focused psychotherapy , CAM , exercise , and SGAs . Outcomes assessed included benefits in response ( often defined as 50 % improvement in HAM-D scores ) , remission ( often defined as a HAM-D score 7 ) , speed of response , speed of remission , relapse , quality of life , functional capacity ( as assessed by various scales ) , reduction of suicidality , or reduction of hospitalization . Harms assessed included overall adverse events , withdrawals because of adverse events , serious adverse events , and specific adverse events . Quality of life , functional status , suicidality , and hospitalizations were rarely reported . Grading the Evidence and Developing Recommendations This guideline was developed by the ACP Clinical Guidelines Committee according to the ACP guideline development process , which has been described ( 10 ) . The Clinical Guidelines Committee used the evidence tables in the accompanying systematic review and full report ( 9 ) when reporting the evidence and grade d the recommendations using ACP 's guideline grading system ( Table 2 ) . Table 2 . The American College of Physicians ' Guideline Grading System * Peer Review The AHRQ evidence review was sent to invited peer review ers and posted on the AHRQ Web site for public comments . The guideline was peer- review ed through the journal and was posted online for comments from ACP Governors and Regents . Comparative Benefits of Pharmacologic Versus Nonpharmacologic Treatment Options for Initial Management Refer to Appendix Table 1 and the accompanying systematic review ( 9 ) for additional details of the evidence . Appendix Table 1 . First-Line Treatment for MDD : SGAs Versus Nonpharmacologic Therapies * SGA Versus Psychological Interventions SGA Versus CBT Monotherapy . Moderate- quality evidence from 5 trials ( 1115 ) showed no difference in response when comparing SGAs ( fluoxetine , fluvoxamine , paroxetine , or sertraline ) with CBT in patients with MDD after 8 to 52 weeks of treatment . Low- quality evidence from 3 trials ( 11 , 14 , 15 ) showed no difference between remission rates ( fluoxetine , fluvoxamine , and paroxetine ) and functional capacity ( 14 ) ( fluvoxamine and paroxetine ) for SGAs compared with CBT . Combination Therapy . Low- quality evidence from 2 trials ( 14 , 16 ) showed no difference in response or remission when comparing monotherapy using SGAs ( escitalopram , fluvoxamine , or paroxetine ) with combination therapy using SGAs plus CBT ( problem-solving therapy or telephone-based CBT ) in patients with MDD after 12 to 52 weeks of treatment . Low- quality evidence from 2 trials ( 14 , 16 ) assessed function , and 1 trial showed that patients who received the combination therapy reported more improvement on 3 of 5 work-functioning measures than those who received SGA monotherapy , although clinical ly important differences on these measures are uncertain . SGA Versus Interpersonal Therapy Monotherapy . Low- quality evidence showed no difference in response ( 1 trial ; escitalopram ) ( 17 ) or remission ( 2 trials ; citalopram , escitalopram , or sertraline ) ( 17 , 18 ) for SGAs compared with interpersonal therapy for patients with MDD after 12 weeks of treatment . Combination Therapy . Low- quality evidence from 1 trial ( 19 ) showed increased remission for SGA monotherapy compared with SGA combined with interpersonal therapy ( with nefazodone ) in patients with MDD after 12 weeks of treatment . SGA Versus Psychodynamic Therapies Monotherapy . Low- quality evidence from 1 trial ( 20 ) showed no difference in remission for fluoxetine compared with psychodynamic monotherapy in patients with MDD after 16 weeks of treatment . Low- quality evidence from 2 trials ( 20 , 21 ) showed few differences in functional capacity between the treatments . Combination Therapy . Low- quality evidence from 1 trial ( 21 ) showed no difference in functional capacity for SGA monotherapy compared with SGA plus psychodynamic combination therapy . SGA Versus CAM Interventions SGA Versus Acupuncture Monotherapy . Low- quality evidence from 2 trials ( 22 , 23 ) showed no difference in treatment response when comparing fluoxetine with acupuncture monotherapy for patients with MDD after 6 weeks of treatment . Combination Therapy . Low- quality evidence from 2 trials ( 24 , 25 ) showed that combination therapy of SGAs with acupuncture improved treatment response compared with monotherapy with SGAs ( fluoxetine or paroxetine ) in patients with MDD after 6 weeks of treatment . However , low- quality evidence from 1 trial ( 24 ) showed no difference in remission when comparing paroxetine monotherapy with paroxetine plus acupuncture combination therapy . SGA Versus -3 Fatty Acids Monotherapy . Low- quality evidence from network meta- analysis showed that SGAs ( fluoxetine ) were associated with a greater response than -3 fatty acids in patients with MDD . SGA Versus SAMe Monotherapy . Low- quality evidence from network meta- analysis showed no difference in response between treatment with escitalopram PURPOSE To determine whether the inhalation of aromatherapy during radiotherapy reduces anxiety . PATIENTS AND METHODS Three hundred thirteen patients undergoing radiotherapy were r and omly assigned to receive either carrier oil with fractionated oils , carrier oil only , or pure essential oils of lavender , bergamot , and cedarwood administered by inhalation concurrently with radiation treatment . Patients underwent assessment by the Hospital Anxiety and Depression Scale ( HADS ) and the Somatic and Psychological Health Report ( SPHERE ) at baseline and at treatment completion . RESULTS There were no significant differences in HADS depression or SPHERE scores between the r and omly assigned groups . However , HADS anxiety scores were significantly lower at treatment completion in the carrier oil only group compared with either of the fragrant arms ( P = .04 ) . CONCLUSION Aromatherapy , as administered in this study , is not beneficial |
12,865 | 21,850,536 | Cox regression analysis revealed pineal location as the only independent adverse prognostic factor .
In conclusion high dose chemotherapy with HSCR might lead to survival primarily in younger children with relapsed sPNET even in the absence of concomitant use of radiotherapy , whereas the outcome in older children and /or in pineal location is extremely poor with this modality | Supratentorial primitive neuroectodermal tumors ( sPNET ) are rare childhood brain tumors .
There is no st and ard strategy for treating relapsed sPNETs .
The role of high dose chemotherapy with hematopoietic stem cell rescue ( HDC with HSCR ) in treating relapsed sPNET is controversial .
A systematic review of the literature regarding outcome of patients with relapsed sPNET treated with HDC and HSCR was performed to examine the potential predictive factors that would justify its use in this subset of patients . | PURPOSE To determine clinical characteristics and response to treatment for children with supratentorial primitive neuroectodermal tumors ( S-PNETs ) . PATIENTS AND METHODS After surgery and staging , 55 patients aged 1.5 to 19.3 years with S-PNETs were r and omized to receive craniospinal radiotherapy ( RT ) followed by eight cycles of 1-(2-chloro-ethyl)-3-cyclohexylnitrosourea ( CCNU ) , vincristine ( VCR ) , and prednisone ( st and ard treatment ) or two cycles of 8-in-1 chemotherapy followed by RT and then eight additional cycles of 8-in-1 . RESULTS Three-year Kaplan-Meier estimates ( estimate + /- SE ) of survival and progression-free survival ( PFS ) rates for patients with confirmed diagnoses of S-PNET were 57 % + /- 8 % and 45 % + /- 8 % , respectively ; survival and PFS rates for children with PNETs located in the pineal region were 73 % + /- 12 % and 61 % + /- 13 % , respectively , and were significantly different from the other S-PNETs ( P < .03 ) . The 8-in-1 arm had greater toxicity than the st and ard-treatment arm . Distributions of PFS between the two treatment groups were not significantly different ( P > .5 ) . Other univariate prognostic factors that influenced PFS included metastasis ( M ) stage ( P < .03 : M0 50 % + /- 9 % v M1 - 4 0 % ) and age ( P < .02 : 1.5 to 2 years 25 % + /- 13 % v > or = 3 years 53 % + /- 9 % ) . CONCLUSION In this first r and omized treatment trial for S-PNETs in children , no significant differences were detected between the two treatment groups . M0 and pineal site of involvement were independent predictors of a better outcome . However , survival was better than previously reported Autologous hematopoietic stem cell transplant ( AHSCT ) has been advocated as a form of salvage therapy for children with high-risk or relapsed brain tumors but only limited data are available currently . We report the outcomes of pediatric brain tumors treated with AHSCT in a quaternary referral center in Hong Kong over 10 years ( June 1996–May 2006 ) . Thirteen patients with medulloblastoma ( n = 9 ) , cerebral primitive neuroectodermal tumor ( n = 1 ) , ependymoma ( n = 1 ) , germ cell tumor ( n = 1 ) and cerebellar rhabdoid ( n = 1 ) were transplanted because of tumor residual ( n = 1 ) or recurrence ( n = 12 ) . Uniform upfront treatment protocol s were adopted according to specific tumor types . Prior to AHSCT , 8 patients ( 61.5 % ) achieved complete remission and 5 ( 38.5 % ) were in partial remission . Conditioning employed thiotepa 300 mg/m2 , etoposide 250 mg/m2 and carboplatin 500 mg/m2 daily for 3 days . Toxicity included mucositis and neutropenic fever in all patients , grade 4 hepatic toxicity in 4 patients ( including hepatic veno-occlusive disease in 2 patients ) and grade 4 renal toxicity in 1 patient . The 5-year event-free survival was 53.9 % . Five patients died of disease recurrence or progression 8–21 months after transplant with a median disease-free period of 8 months post-transplant . One died of transplant-related complications in the early post-transplant period . Seven survived for a median of 5.4 years ( maximum follow-up of 9.8 years ) , with six having Lansky-Karnofsky performance score above 80 . All survivors had complete remission before transplant though 2 had leptomeningeal spread . We conclude that AHSCT can achieve long-term survival in children with recurrent brain tumor . However , those with macroscopic residual tumor before transplant can not be salvaged Current treatment for high risk and recurrent medulloblastoma ( MB ) and supratentorial primitive neuroectodermal tumors ( stPNET ) has a very poor prognosis in children . High dose chemotherapy ( HDCT ) and autologous stem cell rescue have improved survival rates . We present 19 patients ( thirteen classified in the high risk group and six patients with recurrent disease ) that received HDCT and autologous stem cell rescue . In the high risk group [ Med Pediatr Oncol 38 ( 2002 ) 83 ] , all patients underwent neurosurgical debulking . St and ard chemotherapy was prescribed in 10 patients . Radiotherapy was given to 4 patients ( all older than 4 years old ) . In the recurrence disease group [ Childs Nerv Syst 15 ( 1999 ) 498 ] , five patients underwent surgery . Radiotherapy was given to those who were not previously irradiated . The HDCT in twelve patients consisted of busulfan 4 mg/kg/day , orally over 4 days in 6-hourly divided doses and melphalan at a dose of 140 mg/m2/day by intravenous infusion over 5 min on day −1 . Three patients additionally received thiotepa 250 mg/m2/day intravenously over 2 days and four patients additionally received topotecan 2 mg/m2/day over 5 days by intravenous infusion over 30 min . The other seven patients received busulfan and thiotepa at the same doses . Patient ’s stem cells were mobilized with granulocyte colony-stimulating factor at a dose of 12 μg/kg twice daily subcutaneously for four consecutive days . Cryopreserved peripheral blood progenitor cells were re-infused 48 h after completion of chemotherapy . With a median follow-up of 34 months ( range 5–93 ) eight complete responses and one partial response were observed . Three patients died of treatment-related toxicities ( 15 % ) . The 2 year event-free survival was 37.67 ± 14 % in all patients and 57 ± 15 % for the high risk group . Therefore we conclude that HDCT may improve survival rates in patients with high risk/recurrent MB and stPNET despite treatment toxicity PURPOSE This study evaluates the outcome of myeloablative chemotherapy and autologous bone marrow rescue ( ABMR ) with or without radiotherapy in children younger than 6 years of age with recurrent malignant brain tumors who had not previously been exposed to conventional fractionated external-beam irradiation . PATIENTS AND METHODS Patients underwent surgery and /or conventional chemotherapy at the time of recurrence to achieve minimal residual disease ( two of these patients also underwent local single-fraction gamma-knife radiosurgery ) . Myeloablative chemotherapy was then administered with carboplatin , thiotepa , and etoposide ( 16 patients ) , thiotepa and etoposide ( three patients ) , or thiotepa , etoposide , and carmustine ( BCNU ; one patient ) . Autologous bone marrow was re-infused 72 hours after chemotherapy . Twelve patients received external-beam irradiation after recovery from ABMR . RESULTS Twenty patients with recurrent brain tumors aged 0.7 to 5.9 years ( median , 2.9 years ) at ABMR were evaluated . Two patients died of toxicity related to myeloablative therapy . Eight patients died of progressive disease . Ten of 20 ( 50 % ) patients ( primitive neuroectodermal tumor (PNET)/medulloblastoma , three patients ; cerebral PNET , three patients ; glioblastoma multiforme , two patients ; anaplastic astrocytoma , one patient ; pineal PNET , one patient ) are alive and disease free at a median of 37.9 months ( range , 9.7 to 98.2 months ) from ABMR ( 3-year overall survival [ OS ] rate of 43 % + /- 13 % and event-free survival [ EFS ] rate of 47 % + /- 14 % ] . Seven of these 10 patients also received irradiation post-ABMR . CONCLUSION Myeloablative chemotherapy with ABMR followed by additional external-beam irradiation appears to be an effective retrieval therapy for some young children with recurrent malignant brain tumors BACKGROUND Single or t and em double high-dose chemotherapy ( HDCT ) was used to treat children with newly diagnosed high-risk or relapsed medulloblastoma and supratentorial primitive neuroectodermal tumor ( MB/sPNET ) in order to defer or avoid radiotherapy in young children . PROCEDURE Thirty-seven HDCTs were given to 25 children with newly diagnosed high-risk or relapsed MB/sPNET . T and em double HDCT was used for 12 of 15 patients initially intended to receive double HDCT . RESULTS Three-year EFS ( + /-SE ) in 6 newly diagnosed high-risk ( > 3 years old ) , 8 newly diagnosed ( <3 years old ) , and 11 relapsed MB/sPNET was 83.3 + /- 15.2 % , 62.5 + /- 20.5 % , and 29.1 + /- 15.7 % , respectively . Three-year EFS for patients in CR or PR and in less than PR at first HDCT was 67.4 + /- 11.0 % and 16.7 + /- 15.2 % , respectively ( P = 0.001 ) . Three-year EFS in patients initially intended to receive double HDCT and single HDCT was 66.0 + /- 12.4 % and 40.0 + /- 15.5 % , respectively . For 19 patients in CR or PR at first HDCT , 3-year EFS was 88.9 + /- 10.5 % in t and em double HDCT group , and 44.4 + /- 16.6 % in single HDCT group , respectively ( P = 0.037 ) . Although four treatment-related mortalities ( TRMs ) occurred during 25 first HDCTs , no TRM occurred during 12 second HDCTs . In four of eight young children , craniospinal radiotherapy was successfully withheld without subsequent relapse . CONCLUSIONS High-dose chemotherapy may improve the survival of children with newly diagnosed high-risk MB/sPNET , and , to some extent , the survival of those with relapsed MB/sPNET . Further study is necessary to eluci date the efficacy of t and em double HDCT PURPOSE To describe the biologic and clinical features of children with primitive neuroectodermal tumors ( PNETs ) arising in the pineal region ( pineoblastomas ) and evaluate prospect ively the efficacy of radiation therapy ( RT ) and /or chemotherapy . PATIENTS AND METHODS Between 1986 and 1992 , 25 children with PNETs of the pineal region were treated as part of a Childrens Cancer Group study . Eight infants less than 18 months of age were nonr and omly treated with eight-drugs-in-1-day chemotherapy without RT . The remaining 17 patients were treated with craniospinal RT and r and omized to receive either vincristine , lomustine ( CCNU ) , and prednisone or the eight-drugs-in-1-day regimen . RESULTS Of 24 completely staged patients , 20 ( 83 % ) had localized disease at diagnosis . All infants developed progressive disease a median of 4 months from the start of treatment . Of the 17 older patients treated with RT and chemotherapy , the Kaplan-Meier estimate of progression-free survival ( PFS ) at 3 years is 61 % + /- 13 % . This is superior to the PFS of children with other supratentorial PNETs ( P = .026 ) . Following RT , 12 of 17 patients ( 70.6 % ) had a residual pineal region mass , which persisted for as long as 5 years before resolving ; only four subsequently developed progressive disease . CONCLUSION ( 1 ) Eight-in-1 chemotherapy without RT appears to be ineffective therapy for young children with PNETs of the pineal region . ( 2 ) For children more than 18 months of age at diagnosis treated with craniospinal RT and chemotherapy , the PFS is superior to that of children with other supratentorial PNETs . ( 3 ) A residual enhancing mass following RT is not predictive of treatment failure BACKGROUND Children with newly diagnosed supratentorial primitive neuroectodermal tumors ( sPNET ) have poor outcomes compared to medulloblastoma patients , despite similar treatments . In an effort to improve overall survival ( OS ) and event-free survival ( EFS ) and to decrease radiation exposure , the Head Start ( HS ) protocol s treated children with newly diagnosed sPNET utilizing intensified induction chemotherapy ( ICHT ) followed by consolidation with myeloablative chemotherapy and autologous hematopoietic cell rescue ( AuHCR ) . PROCEDURES Between 1991 and 2002 , 43 children with sPNET were prospect ively treated on two serial studies ( HS I and II ) . After maximal safe surgical resection , patients on HS I and patients with localized disease on HS II were treated with five cycles of ICHT ( vincristine , cisplatin , cyclophosphamide , and etoposide ) . Patients on HS II with disseminated disease received high-dose methotrexate during ICHT . If the disease remained stable or in response , patients received a single cycle of high-dose myeloablative chemotherapy followed by AuHCR . RESULTS Five-year EFS and OS were 39 % ( 95%CI : 24 % , 53 % ) and 49 ( 95%CI : 33 % , 62 % ) , respectively . Non-pineal sPNET patients faired significantly better than those patients with pineal sPNETs . Metastasis at diagnosis , age , and extent of resection were not significant prognostic factors . Sixty percent of survivors ( 12 of 20 ) are alive without exposure to radiation therapy . CONCLUSIONS ICHT followed by AuHCR in young patients with newly diagnosed sPNET appears to not only provide an improved EFS and OS for patients who typically have a poor prognosis , but also it successfully permitted deferral and elimination of radiation therapy in a significant proportion of patients BACKGROUND Supratentorial PNET ( sPNET ) are rare CNS tumors of embryonal origin arising in children and adults . The treatment of sPNET for all age groups at our cancer center has been based on the management of medulloblastoma ( MB ) , involving neurosurgical debulking followed by cranio-spinal irradiation ( CSI ) and systemic chemotherapy . METHODS Medical records were review ed to gather demographic and clinical data about all embryonal CNS tumors in children and adults from 2001 to 2007 . Tumor pathology , clinical management and survival data were also assessed , particularly as regards those patients who received the Packer chemotherapy regimen for either sPNET or MB . RESULTS Eleven patients ( five children and six adults ) were identified with non-pineal sPNET , three children with pineal sPNET , and 19 patients ( 18 children and 1 adult ) with MB . There was no difference in overall survival ( OS ) rates between pediatric and adult sPNET . When all sPNET were compared to all MB , 5-year OS was 14 % versus 73 % , respectively , but was only 9 % for non-pineal sPNET . When only considering those patients treated with the Packer chemotherapy regimen , the 5-year OS was 12 % for sPNET versus 79 % for MB . CONCLUSION This retrospective study demonstrates that non-pineal sPNET are clinical ly distinct from MB and are resistant to the Packer chemotherapy regimen . We suggest that it is time to reconsider the use of this regimen in teenage and young adult non-pineal sPNET and to investigate the utility of alternative approaches |
12,866 | 28,435,393 | The current evidence from the available clinical studies suggests that S-1 may be an effective and tolerable treatment for advanced HCC . | Hepatocellular carcinoma ( HCC ) is the most common liver neoplasm worldwide .
Based on its potent inhibition of dihydropyrimidine dehydrogenase ( DPD ) , S-1 is expected to be more active than other fluoropyrimidines against HCC with DPD activity .
This systematic review was aim ed to assess the efficacy and safety of S-1 for treatment of advanced HCC . | Aim : S-1 is an oral anticancer fluoropyrimidine formulation consisting of tegafur , 5-chloro-2,4-dihydroxypyridine and potassium oxonate . The aim of this study was to evaluate the pharmacokinetics and bioequivalence of a newly developed generic formulation of S-1 in Chinese cancer patients in comparison with the br and ed reference formulation of S-1 . Methods : A single-dose , r and omized-sequence , open-label , two-way self-crossover study was conducted in 30 Chinese cancer patients . The subjects alternatively received the two formulations ( 40 mg/m2 , po ) with a 7-d interval . Plasma concentrations of FT , CDHP , Oxo , and 5-Fu were determined using LC-MS/MS . Pharmacokinetic parameters , including Cmax , Tmax , t1/2 , AUC0–t , and AUC0–∞ were determined using non-compartmental models with DAS2.0 software . Bioequivalence of the two formulations were to be evaluated according to 90 % CIs for the log-transformed ratios of AUC and Cmax of S-1 . Adverse events were evaluated through monitoring the symptom , physical and laboratory examinations , ECGs and subject interviews . Results : The mean values of Cmax , AUC0–t , and AUC0–∞ of FT , 5-Fu , CDHP , and Oxo for the two formulations had no significant differences . The 90 % CIs for natural log-transformed ratios of Cmax , AUC0–t , and AUC0–∞ were within the predetermined bioequivalence acceptance limits . A total of 11 mild adverse events , including fatigue , nausea and vomiting , anorexia , diarrhea and myelosuppression , were observed , and no serious and special adverse events were found . Conclusion : The newly developed generic formulation and reference formulation of S-1 have similar pharmacokinetics with one dose ( 40 mg/m2 ) in Chinese cancer patients . Both the formulations of S-1 are well tolerated The prognosis of patients with hepatocellular carcinoma ( HCC ) with portal vein tumor thrombosis ( PVTT ) is extremely poor . The aim of this study was to eluci date the efficacy of hepatic arterial infusion chemotherapy ( HAIC ) for patients with advanced HCCs S‐1 , an oral fluoropyrimidine derivative , has been shown to be clinical ly effective against various solid tumors , and pre clinical studies have demonstrated activity against hepatocellular carcinoma . We conducted a phase I/II study in patients with advanced hepatocellular carcinoma to examine the pharmacokinetics , recommended dose , safety and efficacy of S‐1 . In phase I , the administered dose of S‐1 was approximately 64 mg/m2 per day in three patients ( level 1 ) and approximately 80 mg/m2 per day in six patients ( level 2 ) . There was no dose‐limiting toxicity at level 1 , but two patients had dose‐limiting toxicity at level 2 ( grade 3 anorexia and grade 2 rash requiring eight or more consecutive days of rest ) . The recommended dose was finally estimated to be 80 mg/m2 per day . There were no significant differences in the pharmacokinetics of S‐1 between patients with Child‐Pugh A and those with B. In phase II , five of 23 patients ( 21.7 % ) had partial responses . The median progression‐free survival and overall survival were 3.7 and 16.6 months , respectively . The most common toxicities of grade 3 or 4 were elevated serum aspartate aminotransferase levels , hypochromia and thrombocytopenia . In conclusion , S‐1 showed an acceptable toxicity profile and promising antitumor activity for hepatocellular carcinoma , warranting further evaluation in r and omized clinical trials . ( Cancer Sci 2010 ; 101 : 2606–2611 Purpose Although several clinical trials have proven the efficacy of adjuvant S-1 treatment in gastric cancers , it is still unclear which patients receive the most benefit . In this study , we prospect ively recruited patients with locally advanced gastric cancer who had undergone curative resection followed by adjuvant S-1 administration to investigate which factors affect the outcomes . Material s and Methods Between July 2010 and October 2011 , we enrolled 49 patients who underwent curative resection for stage II or III gastric cancer and who subsequently received adjuvant S-1 treatment for 1 year . Results Twenty-nine patients ( 59.2 % ) continued S-1 treatment for 1 year , and 12 patients ( 24.5 % ) experienced recurrent disease during the follow-up period . Patients with continuation of S-1 for 1 year had significantly increased rates of disease-free survival ( P<0.001 ) and overall survival ( P=0.001 ) relative to the patients who discontinued S-1 during year 1 . Multivariate analysis indicated poor outcomes for patients with stage III disease and those who discontinued S-1 treatment . Excluding patients who discontinued S-1 due to cancer progression ( n=7 ) , adjuvant treatment with S-1 still demonstrated a significant difference in the disease-free survival rate between the patients who continued treatment and those who discontinued it ( P=0.020 ) . Conclusions S-1 is tolerated as adjuvant treatment in gastric cancer patients . However , discontinuing S-1 treatment may be an unfavorable factor in the prevention of recurrence . S-1 adjuvant treatment should be continued for 1 year if possible through the proper management of toxicities Hepatocellular carcinoma ( HCC ) with portal venous invasion ( PVI ) has a very poor prognosis , with a median survival of 3 months and virtually no survival at 1 year . The combination of intraarterial 5‐fluorouracil ( FU ) and systemic interferon‐α ( IFNα ) was recently reported to be effective against HCC with PVI , but these were small pilot studies BACKGROUND Most cases of hepatocellular carcinoma occur in the Asia-Pacific region , where chronic hepatitis B infection is an important aetiological factor . Assessing the efficacy and safety of new therapeutic options in an Asia-Pacific population is thus important . We did a multinational phase III , r and omised , double-blind , placebo-controlled trial to assess the efficacy and safety of sorafenib in patients from the Asia-Pacific region with advanced ( unresectable or metastatic ) hepatocellular carcinoma . METHODS Between Sept 20 , 2005 , and Jan 31 , 2007 , patients with hepatocellular carcinoma who had not received previous systemic therapy and had Child-Pugh liver function class A , were r and omly assigned to receive either oral sorafenib ( 400 mg ) or placebo twice daily in 6-week cycles , with efficacy measured at the end of each 6-week period . Eligible patients were stratified by the presence or absence of macroscopic vascular invasion or extrahepatic spread ( or both ) , Eastern Cooperative Oncology Group performance status , and geographical region . R and omisation was done central ly and in a 2:1 ratio by means of an interactive voice-response system . There was no predefined primary endpoint ; overall survival , time to progression ( TTP ) , time to symptomatic progression ( TTSP ) , disease control rate ( DCR ) , and safety were assessed . Efficacy analyses were done by intention to treat . This trial is registered with Clinical Trials.gov , number NCT00492752 . FINDINGS 271 patients from 23 centres in China , South Korea , and Taiwan were enrolled in the study . Of these , 226 patients were r and omly assigned to the experimental group ( n=150 ) or to the placebo group ( n=76 ) . Median overall survival was 6.5 months ( 95 % CI 5.56 - 7.56 ) in patients treated with sorafenib , compared with 4.2 months ( 3.75 - 5.46 ) in those who received placebo ( hazard ratio [ HR ] 0.68 [ 95 % CI 0.50 - 0.93 ] ; p=0.014 ) . Median TTP was 2.8 months ( 2.63 - 3.58 ) in the sorafenib group compared with 1.4 months ( 1.35 - 1.55 ) in the placebo group ( HR 0.57 [ 0.42 - 0.79 ] ; p=0.0005 ) . The most frequently reported grade 3/4 drug-related adverse events in the 149 assessable patients treated with sorafenib were h and -foot skin reaction ( HFSR ; 16 patients [ 10.7 % ] ) , diarrhoea ( nine patients [ 6.0 % ] ) , and fatigue ( five patients [ 3.4 % ] ) . The most common adverse events result ing in dose reductions were HFSR ( 17 patients [ 11.4 % ] ) and diarrhoea ( 11 patients [ 7.4 % ] ) ; these adverse events rarely led to discontinuation . INTERPRETATION Sorafenib is effective for the treatment of advanced hepatocellular carcinoma in patients from the Asia-Pacific region , and is well tolerated . Taken together with data from the Sorafenib Hepatocellular Carcinoma Assessment R and omised Protocol ( SHARP ) trial , sorafenib seems to be an appropriate option for the treatment of advanced hepatocellular carcinoma Although transcatheter arterial chemoembolization ( TACE ) is considered to be an effective treatment for advanced hepatocellular carcinoma ( HCC ) , it is difficult to achieve complete necrosis by TACE alone due to incomplete embolization and tumor angiogenesis . Recent studies have shown that tegafur/uracil ( UFT ) inhibits tumor angiogenesis in several cancer types . Therefore , this study was conducted to test the efficacy and toxicity of the UFT administration after TACE in advanced HCC . Thirty patients with HCC who had been treated with TACE alone more than three times and had a recurrence within 6 months were enrolled . All of the patients were treated with TACE and 28 patients were r and omly assigned to the UFT ( UFT 300 mg/day , three days after TACE , n=14 ) and control groups ( n=14 ) . The primary end point was the time to treatment failure ( TTF ) and the secondary end points were mainly the response rate and toxicity . Administration and observation were continued up to 6 months after TACE unless local recurrence was detected or serious adverse events developed . The median TTF in the control group was 87 days , whereas in the UFT group it was 127 days , thus significantly prolonged as compared to the control group ( P=0.0016 ) . Moreover , the overall response rate ( 35.7 % ) in the UFT group was significantly higher than that in the control group ( 0 % ) . As for toxicity , only 4 patients in the UFT group developed grade 1 - 2 toxicities such as ascites . Serious complications by TACE were not observed in either group . Notably , there were no increases in the serum VEGF levels in the UFT group whereas those in the control group increased significantly . In conclusion , UFT administration after TACE was an effective treatment and showed no severe adverse events . This regimen may have an adjuvant role and antiangiogenic function in advanced HCC |
12,867 | 12,076,441 | REVIEW ER 'S CONCLUSIONS LAAM appears more effective than methadone at reducing heroin use .
There was no difference in safety observed , although there was not enough evidence to comment on uncommon adverse events | BACKGROUND LAAM and methadone are both full mu opiate agonists and have been shown to reduce dependence on heroin when given continuously under supervised dosing conditions .
LAAM has a long duration of action requiring dosing every two or three days compared to methadone which requires daily dosing .
LAAM is not as widely available internationally as methadone , and may be withdrawn from the market following ten cases of life-threatening cardiac arrhythmias and an association with QT prolongation .
OBJECTIVES To compare the efficacy and acceptability of LAAM maintenance with methadone maintenance in the treatment of heroin dependence . | Sixty subjects participated in a double-blind study comparing methadyl acetate ( 80 mg ) with two dosages of methadone ( 50 mg and 100 mg ) in the maintenance of opiate addicts . The safety of all three regimens was supported and methadyl acetate was as effective as methadone in the retention of subjects Abstract 1-Alpha-acetylmethadol ( LAAM ) maintenance treatment has been proposed as a favorable alternative to methadone maintenance . With an un-obtrusive actometer we recorded two successive 24-h cycles of spontaneous motor activity from 12 patients receiving LAAM every other day , and from five receiving methadone every day . LAAM patients were about 50 % more active on days of drug administration than on no-dose days ( P<0.001 ) . There were no significant day-to-day differences in motility of methadone patients . LAAM administered every other day may significantly modify the human circadian rhythm of spontaneous motility ; further research is thus needed before this treatment is widely akopted Thirty-four drug addicts , aged 20 - 24 years , with a history of 4 - 8 years of intravenous heroin abuse , were r and omly assigned either to a methadone maintenance treatment ( MMT ) ( 17 ) or to an untreated group ( 17 ) . The untreated controls could not apply for entrance to the program until two years later . It was found that after two years 12 MMT patients had ab and oned their drug habits and begun work , whereas 5 had recurrent drug abuse problems . Of the controls , one was drug-free and gainfully employed , 12 were continuously abusing heroin ( 3 of these had incurred potentially fatal diseases in consequence ) , 2 were in prison and 2 had diet . Two to seven years after their first visit to the Psychiatric Research Center 8 of the original control group have been accepted into the program . At present 19 ( out of 25 admitted ) are gainfully employed and no longer abusing drugs . Among the remaining controls 4 are dead , 3 are in prison , one in spite of a serious heart condition abuses heroin and one is drug-free . The rehabilitation rate was thus 76 per cent in the program as compared to 6 per cent among the control group . In addition , MMT obviously reduced the high morbidity and mortality rates found in a selection of heroin addicts who fulfilled the admittance criteria of the Swedish program The authors conducted a 16-week study with nine opioid-dependent individuals ( six male ; four white/two African American/three Hispanic ; age 36.8 + /- 2.2 years ) . Participants were assigned to either a low-dose ( 165 mg/week ; n = 5 ) or high-dose ( 330 mg/week ; n = 4 ) Levo-alpha-acetylmethadol ( LAAM ) condition according to a r and omized , double-blind , within-subjects crossover design , such that they were inducted onto one maintenance dose for 4 weeks and then were crossed over to receive the converse for 4 weeks . Subsequently , individuals underwent detoxification from LAAM . Eight of nine participants completed the study protocol . The proportion of urine sample s positive for opiates was 0.22 + /- 0.08 and 0.53 + /- 0.12 , under the high- and low-dose conditions , respectively ( F = 11.8 ; P = 0.01 ) . These results show that LAAM dose regimen affects the degree of abstinence from opioids Heroin addicts were recruited for a 14-week open clinical comparison of methadone hydrochloride and methadyl acetate . Patients were r and omly assigned to a methadyl acetate clinic in which methadyl acetate was dispensed to patients three times per week or to a methadone clinic in which methadone was dispensed six days per week . No statistically significant differences were observed between groups in retention rates , illicit drug use , employment rates , or arrest rates . The group treated with methadyl acetate had more dropouts in the first seven weeks than the second seven weeks : this pattern was reversed for the methadone-treated group . The differences were significant ( P = .01 ) . Spontaneously reported symptoms suggest that induction with methadyl acetate may be a more clinical ly variable phenomenon than induction with methadone . The reduction of number of clinic visits in the group treated with methadyl acetate was not a source of variance in treatment effectiveness Heroin addicts who had been maintained for at least three months on LAAM ( levo-alpha-acetylmethadol , methadyl acetate ) and at least three months on methadone were asked to compare the two drugs on a number of criteria . The responses were highly selective , indicating that a desire to please the investigators was not an important factor . Overwhelmingly , the majority of patients reported that LAAM provided better heroin " blockade " , that it was more effective in reducing craving , and that actual use of heroin was less on LAAM than on methadone . In other respects , such as sexual performance , sleep , and appetite , most patients perceived no difference between the drugs . In no respect was methadone preferred by a majority , although methadone was viewed more favorably on some criteria by some patients . These findings indicate that for most heroin addicts LAAM will be an acceptable maintenance drug This was an open clinical trial of methadyl acetate ( LAAM ) compared with methadone in the maintenance of 636 heroin addicts who had previously been stabilized on a maintenance regimen of methadone . The starting sample assembled by the 13 cooperating clinics were r and omly assigned to continued maintenance on methadone (= 308 ) or crossed over to methadyl acetate (= 328 ) for a period of 40 weeks . The starting dose was identical to the previously established dose of methadone , but beginning with the second visit , dosage was flexible . Safety was evaluated by clinical and laboratory observations conducted at four-week intervals throughout the study . Relative efficacy was evaluated by illicit drug use , program retention and attendance , and global staff judgments . It is concluded that methadyl acetate is as safe as methadone and , when given three times a week , is an acceptable and effective maintenance drug for many heroin addicts In a double-blind study carried out between 1972 and 1975 in Hong Kong 100 heroin addict volunteers were initially admitted to hospital for two weeks for stabilisation on 60 mg of methadone before being assigned at r and om to two groups : one group received methadone ( range 30 - -130 mg , average 97 mg/day ) ; those in the other group had their dose of methadone reduced at the rate of 1 mg/day and were then maintained on placebo . All subjects were provided with a broad range of supportive services . After thirty-two weeks 10 % of the controls were still on treatment , compared with 76 % of those receiving methadone . At the end of the three-year project , only 1 of the original 50 placebo subjects still turned up for treatment ( 2 % ) , whereas the retention-rate ( proportion still on treatment ) for methadone subjects was 56 % . Subjects who had dropped out of the study and were readmitted for methadone treatment under known conditions had the same retention-rate as the original treatment group The authors r and omly assigned 95 male narcotic addicts to one of four treatment conditions : either methadone or LAAM maintenance and one of two drug-appropriate clinic attendance schedules . Although no differences were observed among treatment conditions on any of the outcome measures employed , the conclusion that the drugs and attendance regimens were equally efficacious and acceptable was made cautiously due to the relatively small sample size and to the observed trend ( p = . 10 ) in favor of methadone maintenance combined with the 3-day ( LAMM-appropriate ) attendance schedule . There was no evidence of untoward physical effects associated with any of the treatment approaches BACKGROUND Opioid dependence is a chronic , relapsing disorder with important public health implication s. METHODS In a 17-week r and omized study of 220 patients , we compared levomethadyl acetate ( 75 to 115 mg ) , buprenorphine ( 16 to 32 mg ) , and high-dose ( 60 to 100 mg ) and low-dose ( 20 mg ) methadone as treatments for opioid dependence . Levomethadyl acetate and buprenorphine were administered three times a week . Methadone was administered daily . Doses were individualized except in the group assigned to low-dose methadone . Patients with poor responses to treatment were switched to methadone . RESULTS There were 55 patients in each group ; 51 percent completed the trial . The mean ( + /-SE ) number of days that a patient remained in the study was significantly higher for those receiving levomethadyl acetate ( 89+/-6 ) , buprenorphine ( 96+/-4 ) , and high-dose methadone ( 105+/-4 ) than for those receiving low-dose methadone ( 70+/-4 , P<0.001 ) . Continued participation was also significantly more frequent among patients receiving high-dose methadone than among those receiving levomethadyl acetate ( P=0.02 ) . The percentage of patients with 12 or more consecutive opioid-negative urine specimens was 36 percent in the levomethadyl acetate group , 26 percent in the buprenorphine group , 28 percent in the high-dose methadone group , and 8 percent in the low-dose methadone group ( P=0.005 ) . At the time of their last report , patients reported on a scale of 0 to 100 that their drug problem had a mean severity of 35 with levomethadyl acetate , 34 with buprenorphine , 38 with high-dose methadone , and 53 with low-dose methadone ( P=0.002 ) . CONCLUSIONS As compared with low-dose methadone , levomethadyl acetate , buprenorphine , and high-dose methadone substantially reduce the use of illicit opioids This was a double-blind comparison of methadyl acetate and two dose levels of methadone hydrochloride in the maintenance of 430 street heroin addicts from 12 Veterans Administration hospitals . The starting sample consisted of 146 patients receiving low-dose methadone , 142 patients receiving methadyl acetate . Patients were first given 30 mg of both drugs , and doses were incremented by 10 mg/week until they stabilized at methadyl acetate , 80 mg three times a week , and methadone hydrochloride , 50 mg daily or 100 mg daily . Dosage was fixed for the balance of the 40-week treatment period . Safety was evaluated by clinical and laboratory observations conducted at frequent intervals throughout the study . Relative efficacy was evaluated by illicit drug use , program retention and attendance , and global staff judgments . It is concluded that methadyl acetate is as safe a drug as methadone and that it compares favorably with highdose methoadone in terms of efficacy . Both methyadyl acetate and high-dose methadone appear to be better maintenance regimens than low-dose methadone under the conditions of this study Sixty-eight heroin addicts maintained for 40 weeks on a regimen of methadyl acetate or methadone hydrochloride in a double-blind study were transferred to a uniform dose of 60 mg of methadone daily at the end of their tenure in the study . They were observed for the ensuing six weeks , during which their daily methadone doses were adjusted according to their clinical needs . Patients were observed for symptoms and signs of discomfort and for the amount of illicit drug use during this period of transition . The results indicate that patients maintained on a regimen of methadyl acetate can be readily restabilized with methadone and that sudden decrease of the methadone dose tends to result in the patient 's supplementing with illicit heroin . Conversely , increasing methadone doses result ed in a corresponding reduction in illicit drug use . It is suggested that a chronic covert abstinence syndrome may exist in some patients receiving long-term methadone maintenance therapy , and that while it may contribute to their continued illicit drug use , it may have a different pathophysiologic basis and require different therapeutic considerations Ten volunteer patients participating in a methadone hydrochloride maintenance program were assigned r and omly to experimental ( five patients ) or control ( five patients ) groups . These patients had been in treatment for several months and had been stabilized ( had no change of dose for at least three weeks ) with methadone prior to inclusion in the study . Patients in the experimental group were given l-methadyl acetate ( l-α acetylmethadol ) on weekends and methadone on weekdays . Patients in the control group were given methadone each day . Clinic attendance , requests for change in medication , and scores on an opiate-withdrawal test instrument did not reveal differences between groups . Clinical observers blind to the experiment were unable to discriminate experimental and control patients . No untoward reactions were observed in either group . These preliminary observations suggest that l-methadyl acetate can be interchanged repeatedly with methadone without difficulty A r and omized clinical trial compared four methods of outpatient withdrawal from heroin . Sixty-one subjects were assigned in a double-blind manner to treatment with either methadone or methadyl acetate . Within each drug group , subjects were assigned to detoxification programs either within the st and ard three-week period or in an extended six weeks of treatment . Outcome measures included retention to the end of the dosing schedule , use of illicit drugs during treatment , subjective discomfort , satisfaction , staff ratings of global progress , and durability of change at a three-month follow-up . Methadyl acetate performed similarly to methadone in most respects . Six-week withdrawal showed some temporary benefits over st and ard treatment , but these advantages should be weighed against the greater cost of the longer treatment and similarity of follow-up outcome BACKGROUND Interim methadone maintenance has been proposed as a method of providing clinical ly effective services to heroin addicts waiting for treatment in st and ard comprehensive methadone maintenance programs . METHODS A clinic that provided initial medical evaluation , methadone medication , and AIDS education , but did not include formal drug abuse counseling or other social support services was established in New York City . A sample of 301 volunteer subjects recruited from the waiting list for treatment in the Beth Israel methadone program were r and omly assigned to immediate entry into the interim clinic or a control group . RESULTS There were no differences in initial levels of illicit drug use across the experimental and control groups . One-month urinalysis follow-up data showed a significant reduction in heroin use in the experimental group ( from 63 % positive at intake to 29 % positive ) with no change in the control group ( 62 % to 60 % positive ) . No significant change was observed in cocaine urinalyses ( approximately 70 % positive for both groups at intake and follow-up ) . A higher percentage of the experimental group were in treatment at 16-month follow-up ( 72 % vs 56 % ) . CONCLUSIONS Limited services interim methadone maintenance can reduce heroin use among persons awaiting entry into comprehensive treatment and increase the percentage entering treatment Chromosomes of peripheral leukocytes were examined in 28 addicts participating in a Veterans Administration-Special Action Office for Drug Abuse Prevention ( SAODAP ) cooperative study of methadyl acetate vs methadone . Blood sample s for 72-hour leukocyte cultures were drawn after nearly 40 weeks of maintenance therapy while subjects were receiving active medication . For comparison , ten nondrug users were also studied . The frequency of chromosome damage was not greater in subjects maintained on methadyl acetate or methadone than in nondrug users Studies of relative LAAM-methadone preference have indicated that a significant proportion of patients prefer levo-alpha-acetylmethadol ( LAAM ) . The present study was design ed to determine whether this preference is associated with better treatment outcomes . Sixty-two stable methadone patients participated in a r and omised crossover clinical trial . They received LAAM ( alternate days ) and methadone ( daily ) for 3 months each , followed by a further 6-month period during which they were free to choose between the drugs . LAAM maintenance was associated with a lower rate of heroin use than methadone maintenance based on analysis of morphine concentration in hair and equivalent health outcomes . The majority of subjects showed a preference for LAAM ( n=27 , 69.2 % ) rather than methadone ( n=12 , 30.8 % ) . The main reasons given for the LAAM preference were that it produced less withdrawal ( 39.3 % ) , fewer side effects ( 28.5 % ) , less craving for heroin ( 17.9 % ) , and entailed fewer pick-up days ( 14.3 % ) . Those who chose LAAM had lower levels of heroin use during LAAM maintenance , significantly better outcomes on two sub-scales of the SF-36 ( Vitality and Mental Health ) , and reported that they felt more normal and that they were ' held ' better when on LAAM . For those who chose methadone , there were no differences in outcomes between the LAAM and methadone maintenance periods . Preference for LAAM is associated with treatment outcomes as good or better than those with methadone Abstract The potential motivation of criminal addicts for methadone treatment was tested in the New York City Correctional Institute for Men . Of 165 inmates seen , all with records of five or more jail sentences , 116 ( 70 per cent ) applied for treatment after a single interview . None of them had previously made application to the methadone program . Of 18 r and omly selected from all applicants with release date s between January 1 and April 30 , 1968 , 12 were started on methadone before they left jail and then referred to the program for aftercare . None of them became readdicted to heroin , and nine of 12 had no further convictions during the 50 weeks of follow-up study . All of an untreated control group became readdicted after release from jail , and 15 of 16 were convicted of new crimes during the same follow-up period We conducted an open clinical trial of the feasibility of maintaining heroin addicts by administering methadone hydrochloride on Monday through Thursday , methadyl acetate on Friday , and no drug at all on Saturday or Sunday . Sixty-five patients from four participating clinics were r and omly assigned to this schedule and another 71 to a daily methadone comparison group . The patient sample consisted of heroin addicts previously stabilized on a maintenance regimen of methadone . The starting dose of methadyl acetate was identical to the previously established dose of methadone but was flexible within limites thereafter . A greater number of patients in the methadyl acetate group failed to complete the full 40 weeks of the study , particularly because they cl aim ed the medication was not holding . Although this particular use of methadyl acetate on Friday to provide a drug-free weekend does not appear to be widely applicable clinical ly , the fact that at least some patients in the methadyl acetate group tolerated the schedule with little or no illicit drug use or obvious discomfort suggests that the strategy is viable and should not be discarded Forty-eight employed heroin addicts were maintained on daily doses of methadone for four months and then r and omly assigned to continue methadone maintenance or be switched to thrice weekly levo-alpha-acetylmethadol ( LAAM ) . LAAM patients had significantly less illicit drug use and longer treatment retention times than those remaining on methadone . They also preferred LAAM to methadone on nine of 15 criteria such as the dosage schedule , feeling ' normal ' , and reduction of craving for heroin . LAAM may be particularly useful with employed patients owing to the reduced frequency of clinic visits In a comparison of methadone hydrochloride and levomethadyl acetate ( I-alpha-acetylmethadol ) , 20 male , opiate-dependent subjects were assigned at r and om to either regimen . Methadone-treated subjects received methadone hydrochloride , 100 mg daily . Levomethadyl patients received doses on Monday , Wednesday , and Friday only . Four received low doses ( 30 to 50 mg ) , and six received high doses ( 80 mg ) . Both regimens were well tolerated . At six months , eight of ten methadone-treated patients and eight of nine levomethadyl-treated patients were undergoing treatment . In patient acceptance , withdrawal symptoms , response to heroin challenges , and number of positive results for urine tests measured for morphine , the two groups were equivalent . Levomethadyl acetate , 80 mg administered three times per week , is equivalent to daily administration of 100 mg of methadone hydrochloride . Large-scale clinical trials of levomethadyl acetate are suggested NE MAJOR PROBLEM with methadone in the maintenance approach to treatment of addiction is its short duration of action , requiring daily administration and often entailing daily clinic attendance . When more than one day ’s supply is given with take-home privileges , the likelihood of illegal dispersion and accidental ingestion by nonaddicted individuals is created . The requirements of daily clinic attendance become an interference with the patient ’s way of life and might be considered a form of dependence in its own right . LAAM ( I-alpha-acetylmethadol ) , a longer acting compound chemically similar to methadone , has the potential for preventing the problems associated with methadone . Since LAAM prevents withdrawal for more than 48 hr , it is necessary to administer it only three times weekly , thus limiting administration of medication to the clinic and requiring patients to report to the clinic less often . Consequently , the anticipated advantages of LAAM are that its use would curtail illegal dispersion of a drug of dependence and at the same time allow patients to lead more conventional lives , being less dependent on the clinic . According to Blachly , David , and Irwin , I the major advantages of LAAM are : ( 1 ) it will suppress abstinence symptoms for about twice as long as methadone : ( 2 ) its action is “ smoother ; ” ( 3 ) there is less complaint of “ nodding ; ” ( 4 ) it is more effective orally than parenterally , hence it is less likely to be abused ; and ( 5 ) there is less subjective euphoria . Its major disadvantages are the occurrence of : ( 1 ) a subjective amphetamine-like effect and dysphoria in some patients ; ( 2 ) occasional complaints of feeling less “ mellow ; ” and ( 3 ) occasional complaints of abdominal cramps . In their comparison of methadone and LAAM , Blachly , David , and Irwin reported that EEG abnormalities were present in 53 % of all patients , 63 % of those on methadone , and 38.5 % of those on LAAM , and that fasting hyperglycemia occurred in 62 % of the LAAM patients as opposed to 2 1 % of those on methadone . Only the latter difference was significant In a double-blind controlled study , d1-α-acetylmethadol hydrochloride a synthetic congener of methadone hydrochloride with a 72- to 96-hour duration of action was compared to methadone in the treatment of long-term compulsive heroin users . The subjects were ambulatory patients whose conditions were already stabilized with oral administration of methadone . Over a five-week period of observation there were no differences in social adjustment between those patients whose conditions were maintained with a daily methadone regimen and those given d1-α-acetylmethadol three times a week |
12,868 | 19,329,444 | RESULTS The studies comparing screening versus no screening showed an improvement of speech development of children in the screening group compared with the group without screening .
Early treatment was associated with better language development in comparison to children with later treatment .
The authors concluded that there is a lack of high- quality evidence regarding all elements of newborn hearing screening .
Early identification and early treatment of children with hearing impairments may be associated with advantages in language development . | BACKGROUND The authors aim ed to evaluate the benefits and harms of universal newborn hearing screening programmes in the detection of hearing impairment . | The aim of this study is to compare pass rates for two different hearing screening methods in well newborns as a function of age . Hearing screening tests were performed on 400 ears in 200 healthy newborn infants at the University of california-Irvine Medical Center . The screening methods used were automated auditory brainstem response ( ABR ) and click evoked otoacoustic emissions ( EOAE ) . The infants ' ages ranged from 5 to 120 h , with an average age of 24 h. Overall , 88.5 % of ears passed the ABR screen , and 79 % passed the EOAE screen . There was no significant difference in the ABR pass rate for infants aged 0 - 24 h of age as compared with infants aged > 24 h compared with the group aged 0 - 24 h ( P < 0.01 ) . Results are compared with earlier studies and implication s for universal hearing screening are discussed OBJECTIVE The objective of this study was to evaluate the accuracy and cost effectiveness of three different methods of hearing screening in newborns . DESIGN A prospect i ve , r and omized cohort design was used . One hundred and five newborns were tested in this preliminary study . SETTING The study was conducted in a tertiary care hospital setting in both the well baby and special care nurseries . METHODS Consenting subjects had their hearing tested using automated auditory brainstem response ( AABR ) , distortion-product otoacoustic emissions , and click-evoked otoacoustic emissions . The time to perform the tests was recorded and the cost of each test was calculated . MAIN OUTCOME MEASURES The main outcomes measured were the time taken to perform each test , the pass/fail rate for each test , and the estimated cost of the tests . RESULTS In this small cohort of patients , we found that AABR was the most accurate test , but it took longer to perform and was more expensive than either of the otoacoustic emission tests . However , the sensitivity and specificity of otoacoustic emissions were less than that of AABR . Test time decreased as the examiner gained experience , and we anticipate that experience will also result in better accuracy for the otoacoustic emission tests . CONCLUSIONS Hearing screening in a hospital-based newborn population is both feasible and cost effective . Although AABR was more expensive , its better accuracy must be considered . As technology improves , the cost of all three tests will diminish . More robust conclusions can not be made based on this small patient population |
12,869 | 19,687,492 | R and omized , controlled trials have compared the rates of cesarean delivery between women with induction of labor and those with expectant management of pregnancy , and have generally concluded that the cesarean rate was unchanged or lower among the induced group ( 8 , 9 ) . | Induction of labor is increasing in the United Statesfrom 9.5 % of births in 1990 to 22.1 % of births in 2004 ( 1 , 2 ) .
Labor may be induced because of maternal ( for example , diabetes mellitus , unstable cardiac disease , hypertensive disease of pregnancy ) or fetal ( for example , nonreassuring results on antenatal testing , intrauterine growth restriction ) indications .
Induction of labor without a medical indication is termed elective induction of labor and appears to be increasing even more rapidly than induction of labor as a whole ( 35 ) .
Elective induction may be motivated by a variety of reasons .
For example , pregnant women may wish to end their pregnancy because of physical discomfort ; concern that rapidly progressing labor would preclude timely arrival at the hospital or epidural placement ; scheduling issues ; or ongoing concerns for maternal , fetal , or neonatal complications ( 1 ) .
Clinicians caring for pregnant women ( such as obstetricians , family practice physicians , and midwives ) may have similar nonmedical reasons for recommending elective induction of labor for their patients ( 4 ) .
They , too , may wish to end the ongoing risk for complications in the pregnancy , limit their patients ' physical discomfort , or reduce the risks imposed by geographic barriers ( 6 , 7 ) .
Clinicians may also have an incentive to use elective induction for their own economic benefit and scheduling preferences .
However , the commonly held dogma regarding induction of labor is that it increases the risk for cesarean delivery ( 10 ) , which in turn is associated with a host of maternal complications .
In addition , a cesarean delivery in the current pregnancy increases both maternal and neonatal risks in future pregnancies ( 11 , 12 ) .
One critical aspect of the existing literature is the control group used for comparison with elective induction of labor .
For a pregnant woman at a particular gestational age , the choices are to expectantly manage the pregnancy ( no intervention ) or to intervene with an induction of labor .
Expectant management of the pregnancy allows the pregnancy to progress to a future gestational age .
Thus , the woman undergoing expectant management may go into spontaneous labor , or she may require a medically indicated induction of labor at a future gestation because of developing preeclampsia , nonreassuring results on antenatal testing , or postterm pregnancy ( 8) .
One method ological problem with many studies of induction of labor , particularly observational studies , is that women in spontaneous labor are used as a control group .
An underst and ing of the effect of induction of labor on cesarean delivery would help clinicians and policymakers determine the benefits and harms , and thus define a reasonable role for elective induction of labor in current obstetric practice .
In this review , we evaluated the published evidence on the maternal and neonatal risks of elective induction relative to expectant management of pregnancy .
We also evaluated the evidence comparing elective induction of labor with spontaneous labor to demonstrate the reasons for the currently held opinion about the effect of elective induction of labor on cesarean delivery .
Because the comparison between elective induction of labor and spontaneous labor is commonly reported in the observational literature , we present these findings primarily to demonstrate the current state of the existing literature as well as to explore the differential findings between the RCTs and observational studies . | OBJECTIVE : Although repeat cesarean deliveries often are associated with serious morbidity , they account for only a portion of abdominal deliveries and are overlooked when evaluating morbidity . Our objective was to estimate the magnitude of increased maternal morbidity associated with increasing number of cesarean deliveries . METHODS : Prospect i ve observational cohort of 30,132 women who had cesarean delivery without labor in 19 academic centers over 4 years ( 1999–2002 ) . RESULTS : There were 6,201 first ( primary ) , 15,808 second , 6,324 third , 1,452 fourth , 258 fifth , and 89 sixth or more cesarean deliveries . The risks of placenta accreta , cystotomy , bowel injury , ureteral injury , and ileus , the need for postoperative ventilation , intensive care unit admission , hysterectomy , and blood transfusion requiring 4 or more units , and the duration of operative time and hospital stay significantly increased with increasing number of cesarean deliveries . Placenta accreta was present in 15 ( 0.24 % ) , 49 ( 0.31 % ) , 36 ( 0.57 % ) , 31 ( 2.13 % ) , 6 ( 2.33 % ) , and 6 ( 6.74 % ) women undergoing their first , second , third , fourth , fifth , and sixth or more cesarean deliveries , respectively . Hysterectomy was required in 40 ( 0.65 % ) first , 67 ( 0.42 % ) second , 57 ( 0.90 % ) third , 35 ( 2.41 % ) fourth , 9 ( 3.49 % ) fifth , and 8 ( 8.99 % ) sixth or more cesarean deliveries . In the 723 women with previa , the risk for placenta accreta was 3 % , 11 % , 40 % , 61 % , and 67 % for first , second , third , fourth , and fifth or more repeat cesarean deliveries , respectively . CONCLUSION : Because serious maternal morbidity increases progressively with increasing number of cesarean deliveries , the number of intended pregnancies should be considered during counseling regarding elective repeat cesarean operation versus a trial of labor and when debating the merits of elective primary cesarean delivery . LEVEL OF EVIDENCE : OBJECTIVE : To compare induction of labor at gestational age 41 weeks with expectant management in regard to neonatal morbidity . Secondary aims were to assess the effect of these managements on mode of delivery and maternal complications . METHODS : Between September 2002 and July 2004 , postterm women with singleton cephalic presentation and no prelabor rupture of membranes were r and omly assigned to induction of labor at 289 days or antenatal fetal surveillance every third day until spontaneous labor . Main outcome measures were neonatal morbidity , operative delivery rates , and maternal complications . RESULTS : Five hundred eight women were r and omly assigned , 254 in each group . No differences of clinical importance were observed in women in whom labor was induced compared with women who were expectantly managed with regard to the following outcomes : neonates whose 5-minute Apgar score was less than 7 ( three neonates in the induction group compared with four in the monitoring group , P=.72 ) ; neonates whose umbilical cord pH was less than 7 ( three compared with two , P=.69 ) ; prevalence of cesarean delivery ( 28 compared with 33 , P=.50 ) ; or prevalence of operative vaginal delivery ( 32 compared with 27 , P=.49 ) . In the induction group more women had precipitate labors ( 33 compared with 12 , P<.01 ; number needed to treat was 13 ) , and the duration of second stage of labor was more often less than 15 minutes ( 94 compared with 56 , P<.01 ; number needed to treat was 7 ) . CONCLUSION : No differences were found between the induced and monitored groups regarding neonatal morbidity or mode of delivery , and the outcomes were generally good . CLINICAL TRIAL REGISTRATION : Clinical Trials.gov , www . clinical trials.gov , NCT00385229 LEVEL OF EVIDENCE : OBJECTIVE To clarify the safety of elective induction of labor at 39 weeks of gestation . STUDY DESIGN Prospect i ve r and omized study . SUBJECTS AND METHODS Uncomplicated nulliparas ( N = 194 ) were r and omly assigned at 36 weeks of gestation . Labor was electively induced in 63 women at 39 weeks of gestation in the active management group ( I group , N = 98 ) . Spontaneous labor onset was expected with semi-weekly nonstress test ( NST ) and amniotic fluid index ( AFI ) by 42 weeks of gestation in the expectant group ( E group , N = 96 ) . Perinatal events were compared between the 2 groups . RESULTS A significantly higher incidence of meconium-stained amnios ( 19.4 % vs 3.2 % ) and fetal resuscitation ( 16.7 % vs 4.8 % ) was found in the E group than in the I group . Also , although a significantly higher incidence of epidural analgesia was noted in the I group ( 89 % ) than in the E group ( 54 % ) ( labor onset > or = 39 weeks , N = 72 ) , the duration of the 1st stage was shorter in I group and the duration of the 2nd stage was not significantly different . No other significant difference was noted between the 2 groups in terms of the rate of C-section , blood loss , incidence of pathological FHR , birth weight , Apgar score , umbilical arterial pH , or admission to NICU . CONCLUSION Active management of labor at 39 weeks could be made as safely as expectant management with modified biophysical profile monitoring OBJECTIVE Studies of cesarean delivery ( CD ) rates among women undergoing induction of labor ( IOL ) often compare such women to women experiencing spontaneous labor at similar gestational ages . We sought to examine the association between IOL at various gestational ages and CD , accounting for the effect of increased gestational age among the comparison group who were managed expectantly . STUDY DESIGN We conducted a retrospective cohort study of all term , singleton , cephalic presentation pregnancies delivered at our institution over 15 years excluding cesarean deliveries before labor . For each gestational age of induction , we created a comparison group of women who were undelivered at that gestational age , and who experienced labor at some future gestational age . RESULTS In women undergoing IOL at 38 weeks gestation , the CD rate was 11.9 % as compared to 13.3 % ( P = .42 ) of women beyond 38 weeks gestation . The CD rate for induction of labor compared to ongoing pregnancy was 14.3 % versus 15.0 % ( P = .62 ) at 39 weeks , 20.4 % versus 19.0 % ( P = .41 ) at 40 weeks , and 24.3 % versus 26.0 % ( P = .39 ) at 41 weeks . When controlling for potential confounding , there was a higher rate of CD among women with expectant management beyond 38 weeks ( adjusted odds ratio [ AOR ] 1.80 ; 95 % CI 1.29 - 2.53 ) , 39 weeks ( 1.39 ; 95 % CI 1.08 - 1.80 ) , and 40 weeks ( AOR 1.27 ; 95 % CI 1.00 - 1.62 ) . CONCLUSION Our findings suggest that IOL may not increase a woman 's risk of CD when compared to expectant management . While this question has been addressed prospect ively at 41 weeks gestation , it requires further examination at earlier gestations and among various subgroups A prospect i ve r and omized controlled trial design ed to investigate selective planned delivery is reported : 264 obstetrically normal women in the 38th week of pregnancy were admitted to this trial and 184 completed it . The infants of mothers in the planned delivery group had higher serum bilirubin levels on the fifth day post partum than control infants but no baby required treatment for hyperbilirubinaemia . Mothers in the planned delivery group required significantly greater amounts of pethidine while control mothers had a significantly higher incidence of meconium staining of the amniotic fluid . However , the infants in the two groups had similar Apgar scores at birth . There was one stillbirth in the control group ; this was due to unrecognized fetal hypoxia during labour induced at 42 weeks for postmaturity Abstract . In a prospect i ve r and omized study spontaneous and oxytocin induced labor “ for convenience ” have been compared with respect to uterine activity , duration of labor , the condition of the fetus and the newborn infant . The study consists of 84 normal patients , of whom 43 were induced at full term by amniotomy and oxytocin infusion using the Cardiff Infusion System Mark II ; 41 patients served as controls . No difference in maternal age , number of previous pregnancies and pelvic score one week before the day of delivery were found between the groups . The following parameters were calculated : duration of labor , uterine activity , amount of bleeding in the third stage of labor , number of early and late decelerations as well as number of episodes of bradycardia in the CTG‐recordings , birth weight , Apgar score one and five minutes post‐delivery and blood gases in mother and child 60 seconds after delivery . No significant differences between the two groups were found . It is concluded that there are no increased risks to mother or fetus compared to normal labor provided that there is cephalic presentation and normal pregnancy , careful selection with respect to the length of pregnancy and the condition of the cervix and that the Cardiff infusion system is used with intrauterine pressure recording and continuous fetal heart monitoring BACKGROUND Several r and omized , controlled trials compared the policies of induction of labor and expectant management for women who reach 41 weeks ' gestation , and although they suggest a better outcome for mothers and infants with such a policy in place , controversy continues as to which is the better form of care . The Canadian Multicenter Postterm Pregnancy Trial ( CMPPT ) enrolled 3407 women , of whom 1701 were r and omized to a policy of induction of labor ( induced group ) and 1706 were r and omized to a policy of expectant management ( expectant group ) . Secondary analyses of data from the CMPPT were undertaken to explore a number of controversial issues . METHODS We used data from the CMPPT to explore further the timing of delivery for women enrolled between 41 0/7 and 41 6/7 weeks ' gestation , the potential impact of more liberal use of prostagl and ins on cesarean section rates , and the relative merits of induced versus spontaneous labor in the two groups . RESULTS Most women in the CMPPT ( 89 % ) were enrolled at 41 0/7 to 41 6/7 weeks ' gestation , of whom 86.2 percent in the induced group and 63.6 percent in the expectant group gave birth before 42 weeks ' gestation . Assuming that administration of prostagl and ins would reduce the likelihood of cesarean section by 12 to 15 percent , cesarean section rates were reduced in the induction group from 21.2 percent to 20.8 to 20.9 percent , and in the expectant group from 24.5 percent 23.3 to 24.2 percent . If labor was induced as part of a policy of expectant management , the cesarean section rate was much higher ( 33.5 % ) than if labor was either spontaneous or induced as part of a policy of induction ( 18.5 % , 22.4 % ) . CONCLUSIONS Women should be informed of the benefits and risks associated with the policies of induction of labor and expectant management , and their preferences regarding these policies should be respected The effect of induction of labor on the neonatal bilirubin levels was investigated in a prospect i ve r and omized study . Forty‐three infants born after elective induction with oxytocin using the Cardiff infusion system and 38 infants born after spontaneous delivery were studied . Several factors other than oxytocin administration which could influence the bilirubin levels such as gestational age , placental transfusion and feeding routines did not differ between the two groups . There were no differences with regard to pH in umbilical vein , Apgar scores , haemoglobin and erythrocyte volume fractions or bilirubin levels neonatally . Thus there was no evidence of an association between induction of labor with oxytocin and jaundice during the neonatal period OBJECTIVE To compare the obstetric outcome of induction of labor at 41 weeks and of follow-up until 42 weeks and induction if the patient has still not given birth at 42 weeks . STUDY DESIGN Six hundred women at 287+/-1 days of gestation with definitely unfavorable cervical scores were r and omized to labor induction ( N=300 ) or spontaneous follow-up ( N=300 ) with twice-weekly nonstress testing and amniotic fluid measurement and once-weekly biophysical scoring . The treatments used in the induction group were ( 1 ) vaginal administration of 50 microg misoprostol ( n=100 ) , ( 2 ) oxytocin induction ( n=100 ) , and ( 3 ) transcervical insertion of a Foley balloon ( n=100 ) . The primary outcome measures were the cesarean delivery rate , whether or not the normal hospital stay had to be extended , and the neonatal outcomes . Secondary outcome measure included number of emergency cesarean deliveries performed for abnormalities of the fetal heart rate ( FHR ) . RESULTS The abdominal delivery rate was 19.3 % in the induction group and 22 % in the follow-up group ( p=0.4 ) . The mean length of hospital stay in the two main groups was 1.4+/-0.8 days and 1.3+/-1 days , respectively ( p=0.1 ) . Significantly higher rates of macrosomia and shoulder dystocia were seen in the follow-up group ( 24.6 and 2.3 % ) than in the induction group ( 7.6 % , p<0.001 ; 0.3 % , p=0.03 ) . Meconium-stained amniotic fluid and meconium aspiration syndrome were observed significantly less frequently in the induction group ( 9.3 and 1.3 % ) than in the follow-up group ( 20.3 % , p<0.001 ; 4 % , p=0.03 ) . Rates of emergency abdominal delivery in response to worrying FHR traces , neonatal intensive care unit admission , and low umblical artery pH were similar in the two groups . There was one intrauterine fetal death in the follow-up group . CONCLUSION Induction of labor at 41 weeks of gestation does not increase the cesarean delivery rate or cause a longer stay in hospital than follow-up until 42 weeks , and neonatal morbidity is also lower after induction In a prospect i ve , r and omised trial , 111 obstetrically normal pregnant women , who had elective induction of labour performed between 39 and 40 weeks , were compared with 117 controls who were managed expectantly until 41 weeks . Compared with the controls , the patients who had elective induction of labour had significantly less meconium staining in labour and a smaller blood-loss after delivery . The mean length of labour , the amount of pethidine used , and the Apgar scores at 1 minute were similar in the two groups . In the electively induced group , the caesarean-section rate was lower and the use of epidural analgesia more common than in the controls , but the differences were mot statistically signficant . The hour of delivery was similar in the two groups , suggesting that convenience to medical and nursing staff would not be greatly changed by elective induction of labour . There was no evidence that the hazards to mother and child were increased by elective induction , and its use might improve perinatal mortality by reducing the number of unexplained mature stillbirths EDITORIAL COMMENT : This observational study makes the valuable point that the outcomes of labour and delivery where labour was induced for nonmedical indications , were comparable for the outcomes of spontaneous labour . As the authors point out this challenges the premise of the RACOG Obstetric Indicator which suggests that induction of labour for ‘ nondefined ’ indications should be kept to a minimum . This implies that labour can properly be induced for ‘ social ’ indications without concern for increasing the rate of birth complications . However , as the authors point out , this conclusion requires further testing in a prospect i ve study where the state of the cervix is evaluated Objective . To determine if elective induction ( IND ) increases the risk of cesarean delivery compared to expectant management ( EM ) . Methods . A r and omized clinical trial involving women ⩾39 weeks ' gestation , according to strict dating criteria , with a Bishop score of 5 or more in nulliparous patients and 4 or more in multiparous patients . The control group was expectantly managed and delivered for obstetric indications , but not later than 42 weeks ' gestation . The study had 80 % power to detect a three-fold increase in cesarean delivery . Results . One-hundred- and -sixteen patients ( 45 nulliparous ) were r and omized to IND and 110 ( 58 nulliparous ) to EM . Demographic characteristics were no different between the groups . The cesarean delivery rate in the IND group was 6.9 % ( 8/116 ) compared to 7.3 % ( 8/110 ) in the EM group ( p = NS ) . Rates of cesarean delivery for nulliparous patients r and omized to IND compared to EM were also not significantly different : 13.3 % ( 6/45 ) versus 10.3 % ( 6/58 ) respectively ( p = NS ) . Neonates delivered of IND patients weighed less than those of the EM group ( 3459 ± 347 versus 3604 ± 438 , p = 0.006 ) . Conclusion . In women with favorable Bishop scores , elective induction of labor result ed in no increase in cesarean delivery compared to expectant management Three hundred two low-risk obstetric patients with an unfavorable cervical examination and well-established gestational age of at least 287 days were r and omly selected for management by either antepartum fetal testing or prostagl and in gel cervical ripening followed by aggressive induction of labor and delivery . The patients managed by induction of labor had a lower incidence of meconium-stained amniotic fluid , meconium aspiration , low Apgar scores , postmaturity syndrome , fetal distress , and cesarean delivery than did patients managed with antepartum fetal testing . Our data suggest that prostagl and in gel cervical ripening and induction of labor and delivery by 42 weeks ' gestation may be the most appropriate management for patients with well-established gestational age and an unfavorable cervical examination Objective To investigate the incidence , efficacy , and safety of elective induction in a community teaching hospital over 1 year . Methods This is a retrospective case-control study of rate , safety , and efficacy of all term inductions with vertex presentations judged to be elective by chart analysis . Cases were matched one for one for age , parity , and pay status with controls in spontaneous labor . The elective induction women were compared with those in spontaneous labor using χ2 Student t test , and Fisher exact test . Potential risk factors for cesarean delivery and neonatal intensive care unit ( NICU ) admission were then selected and subjected to bivariate analysis . Stepwise logistic regression was applied to control for confounding and to select which risk factors were important for those end points . Results There were 461 case-control pairs . The elective induction rate was 12.3 % . Cesarean delivery was increased by elective induction in bivariate analysis ( odds ratio [ OR ] = 1.81 , confidence interval [ CI ] = 1.07 , 3.08 ; power = .60 ) . The cesarean delivery rate was 8.7 % ( control 5.0 % ) . In a multiple regression model of potential risk factors for cesar-ean delivery , nulliparity ( OR = 6.14 , CI = 2.90 , 13.04 ) , cervical priming ( OR = 3.06 , CI = 1.46 , 6.40 ) , oxytocin usage ( OR = 2.82 , CI = 1.03 , 7.75 ) , gestational age at least 287 days ( OR = 2.51 , CI = 1.38 , 4.58 ) , and birth weight at least 3800 g ( OR = 2.29 , CI = 1.27 , 4.13 ) were significant , but elective induction and epidural anesthesia were not . Elective induc-tion did not significantly increase the rate of NICU admission ( 4.6 % versus control 3.9 % ) . In a multiple regression model of potential factors predicting NICU admission , only a 5-minute Apgar score of at most 8 was significant ( OR = 12.34 , CI = 6.01 , 25.3 ) . Conclusion Elective induction is commonly practice d , safe , and efficacious . Cesarean delivery is increased signifi-cantly by nulliparity and /or an unfavorable cervix , among other factors , but not by elective induction itself Abstract . The effect of induction of labour on the foetus and the newborn was investigated in a prospect i ve r and omized study . 41 neonates were studied after induction at full term by amniotomy and intravenous oxytocin infusion . The infusion rate was regulated by the intraamniotic pressure using the Cardiff infusion pump system . 39 neonates served as controls where the labour started spontaneously followed by amniotomy . In both groups foetal heart rate monitoring and intraamniotic pressure recordings were performed . There were no differences in Apgar score and pH in cord blood between the groups . The newborns were evaluated the first and the fifth day of life with the Brazelton Neonatal Behavioral Assessment Scale and with a modified Prechtl neurological examination . There were no differences in behaviour and neurological state between the two groups . However , within the groups there were significant differences between the first and the fifth day concerning both neonatal behaviour and neurological state Several authors have stated that induction of labor may have deleterious psychological effects on women 's experiences of labor and early mother-infant interaction . Research on this subject is scarce and in most cases no distinction is made between elective induction and induction for medical reasons . For that reason the observed effects may also have been caused by the medical complications that led to the induction . Differences in experience of labor may also be in part explained by differences in personal characteristics between women choosing or rejecting induction of labor . Influences of induction of labor can only be reliably assessed in prospect i ve studies . In the present study of 271 women with an uncomplicated pregnancy , data regarding their experiences of pregnancy and their expectations of labor and motherhood were collected before labor . In 72 women labor was electively induced , and 199 women had a spontaneous onset of labor . Of 33 women , 19 with spontaneous labor and 14 with elective induction , the first contact with their newborn was observed . All women who could be contacted were interviewed about their experience of labor and the first contact with their infant . Six months after delivery the mothers were question ed about the state of health of mother and infant and about nursing the infant . Mothers with induced labor were rated as being generally less emotionally involved in the first contact with their newborn than mothers with spontaneous labor , but the differences were not significant ( Fig. 1 ) . The duration of spontaneous labor was longer , but the subjective time experience did not differ between groups . Women with spontaneous labor were more tired during labor . ( ABSTRACT TRUNCATED AT 250 WORDS OBJECTIVE : To quantify the risk and risk factors for cesarean delivery associated with medical and elective induction of labor in nulliparous women . METHODS : A prospect i ve cohort study was performed in nulliparous women at term with vertex singleton gestations who had labor induced at 2 obstetrical centers . Medical and elective indications and Bishop scores were recorded before labor induction . Obstetric and neonatal data were analyzed and compared with the results in women with a spontaneous onset of labor . Data were analyzed using univariate and multivariable regression modeling . RESULTS : A total of 1,389 women were included in the study . The cesarean delivery rate was 12.0 % in women with a spontaneous onset of labor ( n = 765 ) , 23.4 % in women undergoing labor induction for medical reasons ( n = 435 ) ( unadjusted odds ratio [ OR ] 2.24 ; 95 % confidence interval [ CI ] 1.64–3.06 ) , and 23.8 % in women whose labor was electively induced ( n = 189 ) ( unadjusted OR 2.29 ; 95 % CI 1.53–3.41 ) . However , after adjusting for the Bishop score at admission , no significant differences in cesarean delivery rates were found among the 3 groups . A Bishop score of 5 or less was a predominant risk factor for a cesarean delivery in all 3 groups ( adjusted OR 2.32 ; 95 % CI 1.66–3.25 ) . Other variables with significantly increased risk for cesarean delivery included maternal age of 30 years or older , body mass index of 31 or higher , use of epidural analgesia during the first stage of labor , and birth weight of 3,500 g or higher . In both induction groups , more newborns required neonatal care , more mothers needed a blood transfusion , and the maternal hospital stay was longer . CONCLUSION : Compared with spontaneous onset of labor , medical and elective induction of labor in nulliparous women at term with a single fetus in cephalic presentation is associated with an increased risk of cesarean delivery , predominantly related to an unfavorable Bishop score at admission . LEVEL OF EVIDENCE : BACKGROUND The rates of perinatal mortality and neonatal morbidity are higher for post-term pregnancies than for term pregnancies . It is not known , however , whether the induction of labor results in better outcomes than does serial fetal monitoring while awaiting spontaneous labor . METHODS We studied 3407 women with uncomplicated pregnancies of 41 or more weeks ' duration . The women were r and omly assigned to undergo induction of labor or to have serial antenatal monitoring and spontaneous labor unless there was evidence of fetal or maternal compromise , in which case labor was induced or cesarean section was performed . In the induction group , labor was induced by the intracervical application of prostagl and in E2 . Serial antenatal monitoring consisted of counts of fetal kicks , nonstress tests , and assessment s of amniotic-fluid volume . The outcomes we measured were the rates of perinatal mortality , neonatal morbidity , and delivery by cesarean section . RESULTS Among the 1701 women in the induction group , 360 ( 21.2 percent ) underwent cesarean section , as compared with 418 ( 24.5 percent ) of the 1706 women in the monitoring group ( P = 0.03 ) . This difference result ed from a lower rate of cesarean section performed because of fetal distress among the women in the induction group ( 5.7 percent vs. 8.3 percent , P = 0.003 ) . When two infants with lethal congenital anomalies were excluded , there were no perinatal deaths in the induction group and two stillbirths in the monitoring group ( P not significant ) . The frequency of neonatal morbidity was similar in the two groups . CONCLUSIONS In post-term pregnancy , the induction of labor results in a lower rate of cesarean section than serial antenatal monitoring ; the rates of perinatal mortality and neonatal morbidity are similar with the two approaches to management Elective induction of labor is still a controversial obstetric procedure . The safety of the procedure and the possibility to program labor during daytime is an often heard argument in favor of it . Also the possibility to prevent term intrauterine fetal death of unknown cause and the possibility to apply fetal monitoring from the beginning of labor are put forward as arguments in favor of elective induction of labor . Feelings of unnaturalness and the dangers of prematurely induced delivery are the most often heard arguments against it . We performed a prospect i ve study to determine the differences between elective induction of labor and spontaneous labor . During 17 consecutive months a group of 184 elective inductions was studied in the Department of Obstetrics , University Hospital - Dijkzigt , Rotterdam . Only healthy women with an uncomplicated pregnancy were included in the study group and all women were allowed a free choice of elective induction or spontaneous labor . The reference group was composed by a system of " matched controls " . For induction of labor a st and ard technique including artificial rupture of the membranes and constant intrauterine fetal monitoring was used . Oxytocin was administered intravenously in an incremental dose . After delivery the acid-base status of the newborns was determined , and part of the newborns were subjected to a neurological screening according to Prechtl . The developments of the infants was followed during one year using a " psychomotor development scheme 0 - 15 months " . ( ABSTRACT TRUNCATED AT 250 WORDS |
12,870 | 24,627,855 | Results : The majority of cross-sectional studies have found children′s obesity directly linked with glycemic index and glycemic load ; however , cohort studies found controversial results .
Also , the intervention studies indicate the negative effect of glycemic index and glycemic load on obesity in children . | Background : Several evidence s have been reported so far in terms of the relationship between obesity and glycemic index and glycemic load in children .
However , the number of review studies that have dealt with recent findings is quite low .
The purpose of present study is to review the existing evidence s in this regard . | BACKGROUND Observational studies in adults suggest that a diet with a high glycemic index ( GI ) or glycemic load ( GL ) , a high intake of sugary foods , or a low fiber intake may increase the risk of overweight . OBJECTIVES We aim ed to examine prospect ively whether dietary GI , GL , added sugar intake , or fiber intake between age 2 and 7 y are associated with the development of body composition . If so , we aim ed to ascertain whether these associations are modified by meal frequency . DESIGN Linear mixed-effect regression analyses were performed in 380 participants of the DOrtmund Nutrition and Anthropometric Longitudinally Design ed ( DONALD ) Study for whom 4 - 6 weighed 3-d dietary records and anthropometric data were obtained between ages 2 and 7 y. RESULTS Changes in dietary GI , GL , or added sugar intake between ages 2 and 7 y were not associated with concurrent changes in percentage body fat ( % BF , as estimated from skinfold thicknesses ) or body mass index SD scores . An increase in fiber intake was related to a concurrent decrease in % BF between ages 2 and 7 y only in children who consumed < 6 meals/d as toddlers ( beta + /- SE from fully adjusted model : -0.26 + /- 0.09%BF per 1-SD increase in fiber intake , P = 0.005 ) , whereas children with a higher meal frequency had no concurrent change ( 0.07 + /- 0.07%BF per 1-SD increase in fiber intake , P = 0.3 ) . CONCLUSIONS Dietary GI , GL , or added sugar intake between ages 2 and 7 y does not appear to influence the development of body composition . Potential benefits associated with increasing fiber intake throughout childhood may be limited to toddlers with a lower meal frequency BACKGROUND Ad libitum , low-carbohydrate diets decrease caloric intake and cause weight loss . It is unclear whether these effects are due to the reduced carbohydrate content of such diets or to their associated increase in protein intake . OBJECTIVE We tested the hypothesis that increasing the protein content while maintaining the carbohydrate content of the diet lowers body weight by decreasing appetite and spontaneous caloric intake . DESIGN Appetite , caloric intake , body weight , and fat mass were measured in 19 subjects placed sequentially on the following diets : a weight-maintaining diet ( 15 % protein , 35 % fat , and 50 % carbohydrate ) for 2 wk , an isocaloric diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 2 wk , and an ad libitum diet ( 30 % protein , 20 % fat , and 50 % carbohydrate ) for 12 wk . Blood was sample d frequently at the end of each diet phase to measure the area under the plasma concentration versus time curve ( AUC ) for insulin , leptin , and ghrelin . RESULTS Satiety was markedly increased with the isocaloric high-protein diet despite an unchanged leptin AUC . Mean ( + /-SE ) spontaneous energy intake decreased by 441 + /- 63 kcal/d , body weight decreased by 4.9 + /- 0.5 kg , and fat mass decreased by 3.7 + /- 0.4 kg with the ad libitum , high-protein diet , despite a significantly decreased leptin AUC and increased ghrelin AUC . CONCLUSIONS An increase in dietary protein from 15 % to 30 % of energy at a constant carbohydrate intake produces a sustained decrease in ad libitum caloric intake that may be mediated by increased central nervous system leptin sensitivity and results in significant weight loss . This anorexic effect of protein may contribute to the weight loss produced by low-carbohydrate diets OBJECTIVE To determine the effects of the Dietary Approaches to Stop Hypertension ( DASH ) eating pattern on cardiometabolic risks in type 2 diabetic patients . RESEARCH DESIGN AND METHODS A r and omized crossover clinical trial was undertaken in 31 type 2 diabetic patients . For 8 weeks , participants were r and omly assigned to a control diet or the DASH eating pattern . RESULTS After following the DASH eating pattern , body weight ( P = 0.007 ) and waist circumference ( P = 0.002 ) reduced significantly . Fasting blood glucose levels and A1C decreased after adoption of the DASH diet ( −29.4 ± 6.3 mg/dl ; P = 0.04 and −1.7 ± 0.1 % ; P = 0.04 , respectively ) . After the DASH diet , the mean change for HDL cholesterol levels was higher ( 4.3 ± 0.9 mg/dl ; P = 0.001 ) and LDL cholesterol was reduced ( −17.2 ± 3.5 mg/dl ; P = 0.02 ) . Additionally , DASH had beneficial effects on systolic ( −13.6 ± 3.5 vs. −3.1 ± 2.7 mmHg ; P = 0.02 ) and diastolic blood pressure ( −9.5 ± 2.6 vs. −0.7 ± 3.3 mmHg ; P = 0.04 ) . CONCLUSIONS Among diabetic patients , the DASH diet had beneficial effects on cardiometabolic risks CONTEXT Dietary factors may trigger or exacerbate the autoimmune disease process . OBJECTIVE Our objective was to examine dietary glycemic index ( GI ) and glycemic load ( GL ) for association with islet autoimmunity ( IA ) development , and progression from IA to type 1 diabetes . DESIGN The Diabetes Autoimmunity Study in the Young follows children at increased genetic type 1 diabetes risk . Diet is collected prospect ively via a parent-reported food frequency question naire . SETTING This was an observational study of children in the Denver area . PATIENTS A total of 1776 Diabetes Autoimmunity Study in the Young children younger than 11.5 yr was included in the study . INTERVENTIONS There were no interventions . MAIN OUTCOME MEASURES IA , defined as the presence of autoantibodies to insulin , glutamic acid decarboxylase , or protein tyrosine phosphatase at two consecutive visits , or the presence of autoantibodies at one visit and diabetic on the next consecutive visit was determined . Type 1 diabetes was diagnosed by a physician . A total of 89 subjects developed IA , and 17 subsequently developed type 1 diabetes during follow-up . Our hypothesis was formulated after data collection . RESULTS GI and GL were not associated with IA development . More rapid progression to type 1 diabetes in children with IA was associated with higher dietary GI ( hazard ratio : 2.20 ; 95 % confidence interval : 1.17 - 4.15 ) and marginally associated with GL ( hazard ratio : 1.59 ; 95 % confidence interval : 0.96 - 2.64 ) at the first IA-positive visit . CONCLUSIONS Higher dietary GI and GL are not associated with IA development , but higher GI is associated with more rapid progression to type 1 diabetes in children with IA , perhaps due to increased dem and on the beta-cell to release insulin . Further study is needed to confirm this finding and identify the underlying biological mechanism Background Glycemic load ( GL ) is the product of glycemic index of a food and amount of available carbohydrate in that food divided by 100 . GL represents quality and quantity of dietary carbohydrate . Little is known about the role of GL in hunger , satiety , and food intake in preschool children . The aim of this study was to investigate the effect of two breakfast meals differing in GL on hunger , satiety , and subsequent food intake at lunch in preschool children aged 4 - 6 y. Methods Twenty three subjects consumed low-GL ( LGL ) and high-GL ( HGL ) breakfast meals according to a r and omized crossover design followed by an ad libitum lunch 4 h after consumption of breakfast . Children were asked to consume meals until they are full . Each treatment was repeated twice in non-consecutive days and data were averaged . Results Children in LGL group consumed significantly lower amounts of GL , total carbohydrate , energy , energy density , and dietary fiber and higher amounts of protein and fat at the breakfast compared to those in HGL group . Prior to lunch , children were hungrier in the HGL intervention group compared to the LGL intervention group ( P < 0.03 ) . However , no significant difference was observed between LGL and HGL intervention groups in the amount of food and energy consumed during lunch . Conclusions Decreased hunger in children prior to lunch in LGL group is likely due to higher protein and fat content of LGL breakfast . Diets that are low in GL can be recommended as part of healthy diet for preschool children The authors prospect ively examined whether change in dietary glycemic index ( GI ) , glycemic load ( GL ) , fiber intake , or whole-grain intake during puberty is associated with concurrent change in percentage of body fat ( % BF ) or body mass index ( BMI ; weight (kg)/height)(2 ) . Linear mixed-effects regression analyses were performed in 215 participants from the Dortmund Nutritional and Anthropometric Longitudinally Design ed ( DONALD ) Study ( Dortmund , Germany ) who possessed weighed 3-day dietary records and anthropometric data at puberty onset ( defined by age at takeoff ) and over the subsequent 4 years ( 1988 - 2007 ) . Neither changes in dietary GI , GL , fiber intake , nor whole-grain intake were associated with concurrent changes in % BF throughout puberty ( change in % BF : -0.03 ( st and ard error ( SE ) , 0.11 ) per st and ard deviation ( SD ) increase in GI ( P = 0.8 ) ; -0.01 ( SE , 0.11 ) per SD increase in GL ( P = 0.9 ) ; 0.02 ( SE , 0.14 ) per SD increase in fiber intake ( P = 0.9 ) ; and 0.09 ( SE , 0.13 ) per SD increase in whole-grain intake ( P = 0.5 ) ) . Similarly , no concurrent associations were observed between these dietary factors and BMI SD scores . Associations of dietary GI with % BF and BMI SD score differed between overweight and normal-weight adolescents ( for concurrent association , P for interaction was 0.03 for % BF and 0.08 for BMI SD score ) . Dietary GI , GL , and fiber and whole-grain intakes in healthy , free-living adolescents do not appear to be relevant to the development of % BF or BMI during puberty UNLABELLED Some short-term pediatric studies have suggested beneficial effects of low glycemic load ( LGL ) meals on feelings of hunger and on energy intake . However , the effects of LGL diets have not been systematic ally studied in obese Hispanic children , who st and to benefit from successful interventions . OBJECTIVE To examine the effects of LGL and high-GL ( HGL ) meals on appetitive responses and ad libitum energy intake of obese Hispanic youth . METHODS A total of 88 obese Hispanic youth aged 7 - 15 years were enrolled in a community-based obesity intervention program and r and omly assigned to consume meals design ed as either LGL ( n = 45 ) or HGL ( n = 43 ) . After 12 weeks , participants were admitted for a 24-hour metabolic study . Following the morning test meal , subjects serially reported hunger , fullness , and satiety using a visual analog scale . Blood insulin and glucose were measured . After 5 hours , participants were fed another test meal and given a snack platter from which to eat ad libitum . All test food was weighed and the energy , macronutrients , and glycemic load ( GL ) of consumed foods were calculated . RESULTS The HGL group had significantly higher insulin ( p = 0.0005 ) and glucose ( p = 0.0001 ) responses to the breakfast meal compared with the LGL group . There were no significant between-group differences in energy consumed from the snack platter ( 1303 vs. 1368 kcal , p = 0.5 ) , or in the subjective feelings of hunger ( p = 0.3 ) , fullness ( p = 0.5 ) or satiety ( p = 0.3 ) between the two groups . CONCLUSIONS Our study provides no evidence that , for obese Hispanic youth , changing the GL of the diet affects short-term hunger , fullness , satiety , or energy intake . Clinical Trials.gov Identifier : NCT01068197 OBJECTIVE Recent reports have suggested that a low glycemic index ( GI ) diet may have a role in the management of obesity through its ability to increase the satiety value of food and modulate appetite . To date , no long-term clinical trials have examined the effect of dietary GI on body weight regulation . The majority of evidence comes from single-day studies , most of which have been conducted in adults . The purpose of this study was to investigate the effect of 3 test breakfasts-low-GI , low-GI with 10 % added sucrose , and high-GI-on ad libitum lunch intake , appetite , and satiety and to compare these with baseline values when habitual breakfast was consumed . METHODS A 3-way crossover study using block r and omization of breakfast type was conducted in a school that already ran a breakfast club . A total of 37 children aged 9 to 12 years ( 15 boys and 22 girls ) completed the study . The proportion of nonoverweight to overweight/obese children was 70:30 . Children were divided into 5 groups , and a rolling program was devised whereby , week by week , each group would r and omly receive 1 of 3 test breakfasts for 3 consecutive days , with a minimum of 5 weeks between the test breakfasts . Participants acted as their own control . The 3 test breakfasts were devised to match the energy and nutritional content of an individual 's habitual breakfast as far as possible . All test breakfasts were composed of fruit juice , cereal , and milk with/without bread and margarine ; foods with an appropriate GI value were selected . After each test breakfast , children were instructed not to eat or drink anything until lunchtime , except water and a small serving of fruit supplying approximately 10 g of carbohydrate , which was provided . Breakfast palatability , satiation after breakfast , and satiety before lunch were measured using rating scales based on previously used tools . Lunch was a buffet-style meal , and children were allowed free access to a range of foods . Lunch was served in the school hall where the rest of the schoolchildren were eating . Food intake at lunch was unobtrusively observed and recorded . Leftovers and food swapping were recorded , and plate waste was estimated . Lunch intakes were analyzed using a multilevel regression model for repeated measures data . The likelihood ratio statistic was used to determine whether the type of breakfast eaten had a significant effect on lunch intake after allowing for sex and weight status . RESULTS The type of breakfast eaten had a statistically significant effect on mean energy intake at lunchtime : lunch intake was lower after low-GI and low-GI with added sucrose breakfasts compared with lunch intake after high-GI and habitual breakfasts ( which were high-GI ) . Overweight and sex did not have a significant effect on lunch intake . Pairwise comparisons among the 3 types of test breakfasts and between each test breakfast and habitual breakfast were made . Lunch intake after the high-GI breakfast was significantly higher than after the low-GI breakfast and low-GI breakfast with added sucrose . The details of the pairwise comparisons were as follows : high-GI versus low-GI = 145 + /- 54 kcal ; high-GI versus low-GI plus sucrose = 119 + /- 53 kcal ; low-GI plus sucrose versus low-GI = 27 + /- 54 kcal . Lunch intake after the low-GI breakfast and the low-GI breakfast with added sucrose was significantly lower than after the habitual breakfast . The details of the pairwise comparisons were as follows : low-GI versus habitual = -109 + /- 75 kcal ; low-GI plus sucrose versus habitual = -83 + /- 75 kcal ; high-GI versus habitual = 36 + /- 75 kcal . There were no significant differences between the test breakfasts in immediate satiation . The high-GI breakfasts were rated to be more palatable than the low-GI breakfasts . At lunchtime , hunger ratings were greater after the high-GI breakfast compared with the other 2 test breakfasts on 2 of the 3 experimental days . Prelunch satiety scales were inversely related to subsequent food intake . CONCLUSIONS These results suggest that low-GI foods eaten at breakfast have a significant impact on food intake at lunch . This is the first study to observe such an effect in a group of normal and overweight children and adds to the growing body of evidence that low-GI foods may have an important role in weight control and obesity management . The potentially confounding effect of differences in the macronutrient and dietary fiber content of the test breakfasts warrants additional study . In addition , the impact of GI on food intake and body weight regulation in the long term needs to be investigated CONTEXT Conventional dietary approaches for the treatment of obesity have generally yielded disappointing results . OBJECTIVE To examine the effects of a low-glycemic index ( GI ) diet compared with a st and ard reduced-fat diet in the management of pediatric obesity . DESIGN Retrospective cohort study of children attending an outpatient pediatric obesity program from September 1997 to December 1998 . SETTING Academic medical center . PARTICIPANTS One hundred seven obese but otherwise healthy children . MAIN OUTCOME MEASURES Changes in body mass index ( BMI [ calculated as weight in kilograms divided by the square of height in meters ] ) and body weight from first to last clinic visit . RESULTS A total of 64 patients received the low glycemic index diet and 43 received the reduced-fat diet for 4.3 vs 4.2 months ' mean duration of follow-up , with 3.3 vs 3.3 mean number of visits , respectively . Body mass index ( -1.53 kg/m(2 ) [ 95 % confidence interval , -1.94 to -1.12 ] vs -0.06 kg/m(2 ) [ -0.56 to + 0 . 44 ] , P<.001 ) and body weight ( -2.03 kg [ 95 % confidence interval -3 . 19 to -0.88 ] vs + 1.31 kg [ -0.11 to + 2.72 ] , P<.001 ) decreased more in the low-GI group compared with the reduced-fat group . In multivariate models , these differences remained significant ( P<.01 ) after adjustment for age , sex , ethnicity , BMI or baseline weight , participation in behavioral modification sessions , and treatment duration . Significantly more patients in the low-GI group experienced a decrease in BMI of at least 3 kg/m(2 ) ( 11 kg/m(2 ) [ 17 . 2 % ] vs. 1 kg/m(2 ) [ 2.3 % ] , P = .03 ) . CONCLUSIONS A low-GI diet seems to be a promising alternative to st and ard dietary treatment for obesity in children . Long-term r and omized controlled trials of a low-GI diet in the prevention and treatment of obesity are needed The objective of the present study was to determine the effects of a long-term moderate-fat diet ( 30 % energy from fat ) v. a low-fat one ( 20 % energy from fat ) on metabolic risks . The study was a r and omised , prospect i ve 14-month trial on overweight and obese patients ( eighty-nine overweight and obese men and women ) . The intervention was a moderate-fat diet ( 30 % energy ) or a low-fat diet ( 20 % energy ) . The main outcome measurements were change in body weight , waist circumference , LDL-cholesterol , HDL-cholesterol , total cholesterol , TAG , and systolic and diastolic blood pressure . Forty-five subjects on the moderate-fat diet and forty-four subjects on the low-fat one were studied . Characteristics of all r and omised participants were similar in both groups . After 7 months , the moderate- and low-fat diets had similar effects on cardiovascular risks . The moderate-fat diet was more successful after 14 months in reducing weight ( -5.0 ( SD 2.5 ) kg in the moderate-fat group v. -1.2 ( SD 1.1 ) kg in the low-fat one ; P < 0.0001 ) , waist circumference ( -5.5 ( SD 2.4 ) cm in the moderate-fat group v. - 2.3 ( SD 1.3 ) cm in the low-fat one ; P < 0.0001 ) , and other cardiovascular risk factors as well ( LDL , TAG , total cholesterol and systolic blood pressure ) . In conclusion , a moderate-fat energy-restricted diet in the long term might have more beneficial effects on weight maintenance and cardiovascular risk factors compared with a low-fat diet . Better dietary adherence with the moderate-fat diet may be the reason for its successful effects Childhood obesity is associated with an increased carotid intima-media thickness ( IMT ) and stiffness . Increased carotid wall thickening and rigidity are considered markers of sub clinical atherosclerosis . The aim of the present study was to test the effect of two hypocaloric diets of varying glycemic index on weight loss and markers of sub clinical atherosclerosis in obese children . Seventy consecutive obese children attending the Outpatient Weight Clinic of the Department of Pediatrics were invited to participate in an intensive dietary protocol . Twenty-six accepted and were r and omly assigned to two different groups : the first group followed a hypocaloric low-glycemic index diet and the second a hypocaloric high-glycemic index diet . Anthropometric measures and biochemical tests were performed in all children . Quantitative B-mode ultrasound scans were used to measure intima-media thickness ( IMT ) and diameters of the common carotid artery . Considering both groups together , at 6 months , body mass index decreased from 28.3 ± 3.1 to 25.8 ± 3.3 kg/m2 , systolic blood pressure from 119 ± 12 to 110 ± 11 mmHg ( P < 0.001 ) , diastolic blood pressure from 78 ± 8 to 74 ± 7 mmHg ( P < 0.001 ) , IMT from 0.48 ± 0.05 to 0.43 ± 0.07 mm ( P < 0.001 ) , stiffness from 3.57 ± 1.04 to 2.98 ± 0.94 mm ( P = 0.002 ) , and high-sensitivity C-reactive protein from 1.5 ± 0.9 ( values log transformed ) to 0.4 ± 1.1 ( P < 0.001 ) . No differences were detectable in fasting serum triglycerides , total cholesterol , and high-density lipoprotein cholesterol . Insulin resistance ( calculated by the HOmeostatic Model Assessment index [ HOMA ] score ) significantly reduced only in the low-glycemic-index diet group ( P < 0.04 ) . In conclusion , this study confirms a benefit of hypocaloric diets on carotid IMT and stiffness in obese children and demonstrates , for the first time , an amelioration of insulin sensitivity in obese children after a low-glycemic index diet . These results justify the advice to obese children to follow a low-glycemic index diet in order to improve their cardiometabolic profile BACKGROUND One in 5 American children is overweight , despite a decrease in total fat consumption . This has sparked an interest in the carbohydrate composition of diets , including the glycemic index ( GI ) . OBJECTIVE To investigate whether a low-GI meal replacement ( LMR ) produced similar metabolic , hormonal , and satiety responses in overweight adolescents as a low-GI whole-food meal ( LWM ) when compared with a moderately high-GI meal replacement ( HMR ) . METHODS R and omized , crossover study comparing LMR , HMR , and LWM in 16 ( 8 male/8 female ) adolescents during 3 separate 24-hour admissions . The meal replacements consisted of a shake and a nutrition bar . Identical test meals were provided at breakfast and lunch . Metabolic and hormonal indices were assessed between meals . Measures of participants ' perceived satiety included hunger scales and ad libitum food intake . RESULTS The incremental areas under the curve for glucose were 46 % and 43 % lower after the LMR and LWM , respectively , compared with the HMR . Insulin 's incremental area under the curve was also significantly lower after both low GI test meals ( LMR = 36 % ; LWM = 51 % ) compared with the HMR . Additional food was requested earlier after the HMR than the LMR ( 3.1 vs 3.9 hours , respectively ) , although voluntary energy intake did not differ . CONCLUSIONS Differences in insulin response between the meal replacements occurred , and prolongation of satiety after the LMR , based on time to request additional food , was observed . We speculate that the prolonged satiety associated with low GI foods may prove an effective method for reducing caloric intake and achieving long-term weight control OBJECTIVE The prevalence of obesity has increased dramatically in recent years . However , the role of dietary composition in body weight regulation remains unclear . The purpose of this work was to investigate the acute effects of dietary glycemic index ( GI ) on energy metabolism and voluntary food intake in obese subjects . METHODS Twelve obese teenage boys were evaluated on three separate occasions using a crossover study protocol . During each evaluation , subjects consumed identical test meals at breakfast and lunch that had a low , medium , or high GI . The high- and medium-GI meals were design ed to have similar macronutrient composition , fiber content , and palatability , and all meals for each subject had equal energy content . After breakfast , plasma and serum concentrations of metabolic fuels and hormones were measured . Ad libitum food intake was determined in the 5-hour period after lunch . RESULTS Voluntary energy intake after the high-GI meal ( 5.8 megajoule [ mJ ] ) was 53 % greater than after the medium-GI meal ( 3.8 mJ ) , and 81 % greater than after the low-GI meal ( 3.2 mJ ) . In addition , compared with the low-GI meal , the high-GI meal result ed in higher serum insulin levels , lower plasma glucagon levels , lower postabsorptive plasma glucose and serum fatty acids levels , and elevation in plasma epinephrine . The area under the glycemic response curve for each test meal accounted for 53 % of the variance in food intake within subjects . CONCLUSIONS The rapid absorption of glucose after consumption of high-GI meals induces a sequence of hormonal and metabolic changes that promote excessive food intake in obese subjects . Additional studies are needed to examine the relationship between dietary GI and long-term body weight regulation OBJECTIVE : To investigate the effect of protein and glycemic index ( GI ) on body composition among European children in the r and omized , 6-month dietary intervention DiOGenes ( diet , obesity , and genes ) family-based study . PATIENTS AND METHODS : In the study , 827 children ( 381 boys and 446 girls ) , aged 5 to 18 years , completed baseline examinations . Families with parents who lost ≥8 % of their weight during an 8-week run-in low-calorie diet period were r and omly assigned to 1 of 5 ad libitum diets : low protein (LP)/low glycemic index ( LGI ) ; LP/high GI ( HGI ) ; high protein (HP)/LGI ; HP/HGI ; and control diet . The target difference was 15 GI U between the LGI/HGI groups and 13 protein percentage points between the LP/HP groups . There were 658 children examined after 4 weeks . Advice on food-choice modification was provided at 6 visits during this period . No advice on weight loss was provided because the focus of the study was the ability of the diets to affect outcomes through appetite regulation . Anthropometric measurements and body composition were assessed at baseline , week 4 , and week 26 . RESULTS : In the study , 465 children ( 58.1 % ) completed all assessment s. The achieved differences between the GI and protein groups were 2.3 GI U and 4.9 protein percentage points , respectively . The LP/HGI group increased body fat percentage significantly more than the other groups ( P = .040 ; partial η2 = 0.039 ) , and the percentage of overweight/obese children in the HP/LGI group decreased significantly during the intervention ( P = .031 ) . CONCLUSIONS : Neither GI nor protein had an isolated effect on body composition . However , the LP/HGI combination increased body fat , whereas the HP/LGI combination was protective against obesity in this sample of children BACKGROUND The incidence of type 2 diabetes increases markedly for obese children after puberty . However , the effect of dietary composition on body weight and diabetes risk factors has not been studied in adolescents . OBJECTIVE To compare the effects of an ad libitum , reduced-glycemic load ( GL ) diet with those of an energy-restricted , reduced-fat diet in obese adolescents . DESIGN R and omized control trial consisting of a 6-month intervention and a 6-month follow-up . MAIN OUTCOME MEASURES Body composition ( body mass index [ BMI ; calculated as weight in kilograms divided by the square of height in meters ] and fat mass ) and insulin resistance ( homeostasis model assessment ) were measured at 0 , 6 , and 12 months . Seven-day food diaries were used as a process measure . SUBJECTS Sixteen obese adolescents aged 13 to 21 years . Intervention Experimental ( reduced-GL ) treatment emphasized selection of foods characterized by a low to moderate glycemic index , with 45 % to 50 % of energy from carbohydrates and 30 % to 35 % from fat . In contrast , conventional ( reduced-fat ) treatment emphasized selection of low-fat products , with 55 % to 60 % of energy from carbohydrates and 25 % to 30 % from fat . RESULTS Fourteen subjects completed the study ( 7 per group ) . The GL decreased significantly in the experimental group , and dietary fat decreased significantly in the conventional group ( P<.05 for both ) . At 12 months , mean + /- SEM BMI ( -1.3 + /- 0.7 vs 0.7 + /- 0.5 ; P = .02 ) and fat mass ( -3.0 + /- 1.6 vs 1.8 + /- 1.0 kg ; P = .01 ) had decreased more in the experimental compared with the conventional group , differences that were material ly unchanged in an intention-to-treat model ( n = 16 ) ( BMI , P = .02 ; fat mass , P = .01 ) . Insulin resistance as measured by means of homeostasis model assessment increased less in the experimental group during the intervention period ( -0.4 + /- 0.9 vs 2.6 + /- 1.2 ; P = .02 ) . In post hoc analyses , GL was a significant predictor of treatment response among both groups ( R2 = 0.51 ; P = .006 ) , whereas dietary fat was not ( R2 = 0.14 ; P = .22 ) . CONCLUSIONS An ad libitum reduced-GL diet appears to be a promising alternative to a conventional diet in obese adolescents . Large-scale r and omized controlled trials are needed to further evaluate the effectiveness of reduced-GL and -glycemic index diets in the treatment of obesity and prevention of type 2 diabetes The aim of the present study was to investigate the effects of long-term intervention of low-glycaemic-index ( GI ) v. high-GI breakfasts on energy and macronutrient intakes in children aged 8 - 11 years . Preadolescent children were assigned to one of two groups in a r and om cross-over design . Each group was given low-GI and high-GI breakfasts on two non-consecutive days per week for 10 weeks per breakfast type . Each breakfast provided approximately 1273 kJ ( 300 kcal ) and was closely matched for macronutrient and dietary fibre content . Subsequent food intake at an ad libitum buffet lunch was recorded and daily energy and macronutrient intakes were measured by 24 h recall and 3 d food diaries . There was a tendency towards a reduced energy intake at lunch following the low-GI breakfast compared with the high-GI breakfast , although the mean difference of 75 kJ ( 18 kcal ) was not significant ( P = 0.406 ) . In particular , there was a trend towards a reduced energy intake in the low-GI arm compared with the high-GI arm among boys . In addition , data from the 3 d food diaries showed that there was a tendency towards a reduced energy intake during the low-GI compared with the high-GI study period . In conclusion , although the difference in energy intake following the low-GI and high-GI breakfasts was not statistically significant , the reduced energy intake following the low-GI breakfast is encouraging . Both dietary fibre and carbohydrate type may affect GI , thus their potential and relative modulating effect on appetite requires further investigation Few studies exist regarding the effects of the Dietary Approaches to Stop Hypertension ( DASH ) diet on novel cardiovascular risk factors among type 2 diabetic patients . We evaluated the effects of the DASH eating pattern on C-reactive protein ( CRP ) level , coagulation abnormalities , and hepatic function tests in type 2 diabetic patients . In this r and omized , crossover clinical trial , 31 type 2 diabetic patients consumed a control diet or the DASH diet for 8 wk . The DASH diet was rich in fruits , vegetables , whole grains , and low-fat dairy products and low in saturated fat , total fat , cholesterol , refined grains , and sweets , with a total of 2400 mg/d sodium . The control diet was a st and ard diet for diabetic patients . There was a 4-wk washout between the 2 trial phases . The main outcome measures were CRP level , coagulation indices , and hepatic function tests . The mean percent change for plasma CRP level was -26.9 ± 3.5 % after the DASH diet period and -5.1 ± 3.8 % after the control diet period ( P = 0.02 ) . Decreases in both alanine aminotransferase and aspartate aminotransferase levels were greater after consuming the DASH diet compared with the control diet ( -14.8 ± 3.0 % vs -6.6 ± 3.4 % ; P = 0.001 ; -29.4 ± 3.7 % vs -5.9 ± 1.4 % ; P = 0.001 , respectively ) . The decrease in the plasma fibrinogen level during the DASH diet period ( -11.4 ± 3.6 % ) was greater than that during the control diet ( 0.5 ± 3.4 % ) ( P = 0.03 ) . Among diabetic patients , the DASH diet can play an important role in reducing inflammation , plasma levels of fibrinogen , and liver aminotransferases . Future longer term studies are recommended BACKGROUND This study was conducted to assess the national prevalence of different grade s of nutritional status ( underweight , normal weight , overweight and obesity ) among Iranian school-students and to compare the prevalence of overweight and obesity using three different sets of criteria . METHODS This cross-sectional national survey was conducted on a representative sample of 21 111 school students including 10 253 boys ( 48.6 % ) and 10 858 girls ( 51.4 % ) aged 6 - 18 years , selected by multistage r and om cluster sampling from urban ( 84.6 % ) and rural ( 15.4 % ) areas of 23 provinces in Iran The percentage of subjects in the corresponding body mass index ( BMI ) categories of the Centers of Disease Control and Prevention ( CDC ) , the International Obesity Task Force ( IOTF ) and the obtained national percentiles were assessed and compared . RESULTS There was no gender differences in BMI , but was higher in boys living in urban than in rural areas ( 18.4 + /- 3.88 vs. 17.86 + /- 3.66 kg/m(2 ) respectively , P < 0.05 ) . The prevalence of underweight was 13.9 % ( 8.1 % of boys and 5.7 % of girls ) according to the CDC percentiles , and 5 % ( 2.6 % of boys and 2.4 % of girls ) according to the obtained percentiles . According to the CDC , IOTF and national cut-offs , the prevalence of overweight was 8.82 % , 11.3 % and 10.1 % respectively ; and the prevalence of obesity was 4.5 % , 2.9 % and 4.79 % respectively . The prevalence of overweight was highest ( 10.98 % ) in the 12-year-old group and that of obesity ( 7.81 % ) in the 6-year-old group . The kappa correlation coefficient was 0.71 between the CDC and IOTF criteria , 0.64 between IOTF and national cut-offs , and 0.77 between CDC and national cut-offs . CONCLUSIONS The findings of this study warrant the necessity of paying special attention to monitoring of the time trends in child obesity based on uniform definitions , as well as to design programmes to prevent and control associated factors |
12,871 | 29,320,966 | Discussion and conclusions Telemedicine is not yet ubiquitous , and barriers vary widely .
The top barriers are technology-specific and could be overcome through training , change-management techniques , and alternating delivery by telemedicine and personal patient-to-provider interaction .
The results of this study identify several barriers that could be eliminated by focused policy . | Introduction and objective Studies on telemedicine have shown success in reducing the geographical and time obstacles incurred in the receipt of care in traditional modalities with the same or greater effectiveness ; however , there are several barriers that need to be addressed in order for telemedicine technology to spread .
The aim of this review is to evaluate barriers to adopting telemedicine worldwide through the analysis of published work . | Background Telehealth ( TH ) and telecare ( TC ) interventions are increasingly valued for supporting self-care in ageing population s ; however , evaluation studies often report high rates of non-participation that are not well understood . This paper reports from a qualitative study nested within a large r and omised controlled trial in the UK : the Whole System Demonstrator ( WSD ) project . It explores barriers to participation and adoption of TH and TC from the perspective of people who declined to participate or withdrew from the trial . Methods Qualitative semi-structured interviews were conducted with 22 people who declined to participate in the trial following explanations of the intervention ( n = 19 ) , or who withdrew from the intervention arm ( n = 3 ) . Participants were recruited from the four trial groups ( with diabetes , chronic obstructive pulmonary disease , heart failure , or social care needs ) ; and all came from the three trial areas ( Cornwall , Kent , east London ) . Observations of home visits where the trial and interventions were first explained were also conducted by shadowing 8 members of health and social care staff visiting 23 people at home . Field notes were made of observational visits and explored alongside interview transcripts to elicit key themes . Results Barriers to adoption of TH and TC associated with non-participation and withdrawal from the trial were identified within the following themes : requirements for technical competence and operation of equipment ; threats to identity , independence and self-care ; expectations and experiences of disruption to services . Respondents held concerns that special skills were needed to operate equipment but these were often based on misunderst and ings . Respondents ’ views were often explained in terms of potential threats to identity associated with positive ageing and self-reliance , and views that interventions could undermine self-care and coping . Finally , participants were reluctant to risk potentially disruptive changes to existing services that were often highly valued . Conclusions These findings regarding perceptions of potential disruption of interventions to identity and services go beyond more common expectations that concerns about privacy and dislike of technology deter uptake . These insights have implication s for health and social care staff indicating that more detailed information and time for discussion could be valuable especially on introduction . It seems especially important for potential recipients to have the opportunity to discuss their expectations and such views might usefully feed back into design and implementation Background Despite the amount of online health information , there are several barriers that limit the Internet ’s adoption as a source of health information . One of these barriers is highlighted in conceptualizations of the digital divide which include the differential possession of Internet skills , or “ eHealth literacy ” . Most measures of Internet skills among population s at large use self- assessment s. The research discussed here applies a multifaceted definition of Internet skills and uses actual performance tests . Objective The purpose of this study was to assess how ready a sample of the general population is for eHealth . More specifically , four types of Internet skills were measured in a performance test in which subjects had to complete health-related assignments on the Internet . Methods From November 1 , 2009 , through February 28 , 2010 , 88 subjects participated in the study . Subjects were r and omly selected from a telephone directory . A selective quota sample was used divided over equal sub sample s of gender , age , and education . Each subject had to accomplish assignments on the Internet . The Internet skills accounted for were categorized as operational ( basic skills to use the Internet ) , formal ( navigation and orientation ) , information ( finding information ) , and strategic ( using the information for personal benefits ) . The tests took approximately 1.5 hours and were conducted in a University office , making the setting equally new for all . Successful completion and time spent on the assignments — the two main outcomes —were directly measured by the test leader . Results The subjects successfully completed an average of 73 % ( 5.8/8 ) of the operational Internet skill tasks and an average of 73 % ( 2.9/4 ) of the formal Internet skill tasks . Of the information Internet skills tasks , an average of 50 % ( 1.5/3 ) was completed successfully and , of the strategic Internet skills tasks , 35 % ( 0.7/2 ) . Only 28 % ( 25/88 ) of the subjects were able to successfully complete all operational skills tasks , 39 % ( 34/88 ) all formal skills tasks , 13 % ( 11/88 ) all information skills tasks , and 20 % ( 18/88 ) both the strategic skill tasks . The time spent on the assignments varied substantially . Age and education were the most important contributors to the operational and formal Internet skills . Regarding the formal Internet skills , years of Internet experience also had some influence . Educational level of attainment was the most important contributor to the information and strategic Internet skills . Conclusions Although the amount of online health-related information and services is consistently growing , it appears that the general population lacks the skills to keep up . Most problematic appear to be the lack of information and strategic Internet skills , which , in the context of health , are very important . The lack of these skills is also problematic for members of younger generations , who are often considered skilled Internet users . This primarily seems to account for the operational and formal Internet skills . The results of the study strongly call for policies to increase the level of Internet skills Background E-health initiatives hold promise to improve shared-care models of health care . In 2008–2011 we developed and trialled web-based software to facilitate a r and omised trial of a shared-care approach for childhood obesity involving General Practitioners ( GPs ) working with tertiary specialists . We describe the software ’s development , implementation and evaluation , and make recommendations for future e-health initiatives . The web-based software was design ed with the goals of allowing both GPs and specialists to communicate and review patient progress ; integrating with existing GP software ; and supporting GPs to deliver the structured intervention . Specifically , we aim ed to highlight the challenges inherent in this process , and report on the extent to which the software ultimately met its implementation and user aims . Methods The study was conducted at the Royal Children ’s Hospital and 22 general practice s across Melbourne , Australia . Participants comprised 30 GPs delivering the shared-care intervention . Outcomes included the following . ( 1 ) GPs ’ pre-specified software requirements : transcribed from two focus groups and analysed for themes using content analysis . ( 2 ) Software implementation and performance based on the experience of the research team and GPs . ( 3 ) GP users ’ evaluation collected via question naire . ( 4 ) Software usage collected via GP question naire and qualified through visual inspection of the software meta- data . Results Software implementation posed difficult and at times disabling technological barriers ( e.g. out- date d hardware , poor internet connections ) . The software ’s speed and inability to seamlessly link with day-to-day software was a source of considerable frustration . Overall , GPs rated software usability as poor , although most ( 68 % ) felt that the structure and functionality of the software was useful . Recommendations for future e-health initiatives include thorough scoping of IT systems and server speed , testing across diverse environments , automated pre-requisite checks and up grade s of processors/memory where necessary , and user-created usernames and passwords . Conclusions GPs are willing to embrace novel technologies to support their practice . However , implementation remains challenging mainly for technical reasons , and this precludes further evaluation of potential user-specific barriers . These findings could inform future e-health ventures into shared-care , and highlight the need for an appropriate infrastructure . Trial registration Australian New Zeal and Clinical Trials Registry : ACTRN126080000553 |
12,872 | 29,845,903 | Weight loss observed in participants who decreased NEAT was double the weight loss found in those who did not compensate , suggesting that the energy imbalance degree may lead to energy conservation .
Future studies should explore the impact of weight-loss magnitude , energetic restriction degree , exercise dose and participant characteristics on NEAT and /or NEPA | Non-exercise physical activity ( NEPA ) and /or non-exercise activity thermogenesis ( NEAT ) reductions may occur from diet and /or exercise-induced negative energy balance interventions , result ing in less-than-expected weight loss .
This systematic review describes the effects of prescribed diet and /or physical activity (PA)/exercise on NEPA and /or NEAT in adults . | Background It has been suggested that exercise training results in compensatory mechanisms that attenuate weight loss . However , this has only been examined with large doses of exercise . The goal of this analysis was to examine actual weight loss compared to predicted weight loss ( compensation ) across different doses of exercise in a controlled trial of sedentary , overweight or obese postmenopausal women ( n = 411 ) . Methodology /Principal Findings Participants were r and omized to a non-exercise control ( n = 94 ) or 1 of 3 exercise groups ; exercise energy expenditure of 4 ( n = 139 ) , 8 ( n = 85 ) , or 12 ( n = 93 ) kcal/kg/week ( KKW ) . Training intensity was set at the heart rate associated with 50 % of each woman 's peak VO2 and the intervention period was 6 months . All exercise was supervised . The main outcomes were actual weight loss , predicted weight loss ( exercise energy expenditure/ 7700 kcal per kg ) , compensation ( actual minus predicted weight loss ) and waist circumference . The study sample had a mean ( SD ) age 57.2 ( 6.3 ) years , BMI of 31.7 ( 3.8 ) kg/m2 , and was 63.5 % Caucasian . The adherence to the intervention was > 99 % in all exercise groups . The mean ( 95 % CI ) weight loss in the 4 , 8 and 12 KKW groups was −1.4 ( −2.0 , −0.8 ) , −2.1 ( −2.9 , −1.4 ) and −1.5 ( −2.2 , −0.8 ) kg , respectively . In the 4 and 8 KKW groups the actual weight loss closely matched the predicted weight loss of −1.0 and −2.0 kg , respectively , result ing in no significant compensation . In the 12 KKW group the actual weight loss was less than the predicted weight loss ( −2.7 kg ) result ing in 1.2 ( 0.5 , 1.9 ) kg of compensation ( P<0.05 compared to 4 and 8 KKW groups ) . All exercise groups had a significant reduction in waist circumference which was independent of changes in weight . Conclusion In this study of previously sedentary , overweight or obese , postmenopausal women we observed no difference in the actual and predicted weight loss with 4 and 8 KKW of exercise ( 72 and 136 minutes respectively ) , while the 12 KKW ( 194 minutes ) produced only about half of the predicted weight loss . However , all exercise groups had a significant reduction in waist circumference which was independent of changes in weight . Trial Registration Clinical Trials.gov NCT The objective of this study was to evaluate the influence of calorie restriction ( CR ) on free-living physical activity levels among humans . Data were from three CALERIE phase I site-specific protocol s. Participants were nonobese ( body mass index = 23.5 - 29.9 kg/m² adults r and omly assigned to 25 % CR , low-calorie diet ( LCD , 890 kcal/day supplement diet until 15 % weight loss , then weight maintenance ) , or control at Pennington Biomedical Research Center ( PBRC ) ; 30 % or 10 % CR at Tufts University ; and 20 % CR or control at Washington University School of Medicine ( WUSM ) . Activity was measured at months 0 , 3 , and 6 ( PBRC ) and at months 0 , 3 , 6 , 9 , and 12 ( WUSM and Tufts ) . Total daily energy expenditure ( TEE ) by doubly labeled water and resting metabolic rate ( RMR ) were used to compute activity energy expenditure : AEE = TEE - RMR - 0.1 * TEE . Accelerometry and 7-day recall categorized activities by intensity . At Tufts , the 10 % and 30 % CR groups experienced significant decreases in AEE at months 6 , 9 , and 12 . At month 6 , a larger decrease in AEE was observed in the CR than the control group at WUSM . At months 3 and 6 , larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC . Accelerometry and 7-day PAR did not consistently detect changes in activity categories . CR-associated changes in AEE were variable but , generally , reduced the energy deficit , which would reduce the expected rate of weight loss . Accelerometry and recall did not consistently explain reduced AEE , suggesting that increased muscle efficiency and /or decreased fidgeting accounted for decreased AEE . Inaccuracy of accelerometry and recall also likely negatively affected sensitivity To test the benefits of aerobic exercise and dietary carbohydrate during reduced-energy feeding , 23 obese women ( 44 + /- 4 % fat ) were r and omly assigned to either aerobic exercise ( Ex ) or no exercise ( Nx ) , and to a low-fat ( LF ) or low-carbohydrate ( LC ) reducing diet ( 5.00 + /- 0.56 MJ/d ) for 12 wk . Changes in body composition , postabsorptive resting metabolic rate ( RMR ) , thermic effect of a meal ( TEM ) , and total daily energy expenditure ( TDEE ) were measured by respiratory gas exchange and doubly labeled water . Significant effects of Ex included a greater loss of fat mass ( Ex : -8.8 + /- 2.1 vs Nx : -6.1 + /- 2.3 kg , P = 0.008 ) and maintenance of TDEE ( Ex : + 0.07 + /- 1.23 vs Nx : -1.46 + /- 1.04 MJ/d , P = 0.004 ) , due to a difference in physical activity ( Ex : + 0.75 + /- 1.06 vs Nx : -0.61 + /- 1.03 MJ/d , P = 0.006 ) , which was not attributable solely to the Ex sessions . RMR in both groups decreased comparably ( -0.54 MJ/d ) , and TEM ( % of meal ) did not change . Diet composition did not significantly influence body composition or energy expenditure changes , but a greater weight loss was observed after the LC than after the LF ( -10.6 + /- 2.0 vs -8.1 + /- 3.0 kg , P = 0.037 ) diet . The addition of aerobic exercise to a low-energy diet was beneficial in the treatment of moderate obesity because of its favorable effects on body composition , physical activity , and TDEE The effects of severe energy restriction alone ( 2.0 MJ/d for 4 wk and subsequently 3.5 MJ/d for 4 wk ) or energy restriction plus moderate exercise on energy balance were studied in 20 healthy obese women . Subjects aged 25 - 50 y were matched on the basis of body mass index and percentage body fat and r and omly assigned to diet alone ( D ) or diet and exercise ( DE ) for 8 wk . DE result ed in a significantly increased loss of fat mass compared with D ( 7.8 + /- 0.8 compared with 5.5 + /- 0.8 kg ; P < 0.05 ) . The average daily metabolic rate measured with doubly labeled water decreased with both treatments , with no differences between the treatments . Energy balance data show that the DE treatment result ed in a significantly greater energy deficit than the D treatment . The relative contribution of fat to energy expenditure during exercise was significantly enhanced by DE treatment whereas it did not change after D. The energy expended on physical activity was not changed at the end of both treatments , with no differences between the two groups . The unchanged energy expended on physical activity indicates that DE might be accompanied by partial compensation of daily physical activities outside the training for the energy expended during the training . The energy deficit due to energy restriction alone was not compensated by a decrease in free-living daily physical activities . Addition of moderate exercise to an energy-restriction program in obese women has advantages with respect to changes in body composition , energy expenditure , and substrate utilization PURPOSE This study aim ed to examine compensatory changes in nonexercise energy expenditure ( NEEx ) and nonexercise physical activity ( NEPA ) in response to an aerobic exercise training program . METHODS Ninety-two overweight/obese ( body mass index , 25 - 39.9 kg·m ) sedentary young adults ( 18 - 30 yr ) completed a 10-month r and omized clinical efficacy trial of aerobic exercise 5 d·wk at either 400 kcal per session ( n = 37 ) , 600 kcal per session ( n = 37 ) , or control ( n = 18 ) . Total daily energy expenditure ( TDEE ) and resting metabolic rate ( RMR ) were measured at months 0 and 10 . NEPA was measured by an accelerometer at months 0 , 3.5 , 7 , and 10 . NEEx was calculated by the following formula : [ ( total daily energy expenditure × 0.9 ) - RMR ] - net EEEx ( EEEx-RMR ) . Mixed modeling was used to examine differences between groups ( group effect ) , within groups ( time effect ) , and group-time interaction for NEEx and NEPA . RESULTS Within the exercise groups , there were no significant effects ( all P > 0.05 ) of group , time , or group-time interaction for NEPA . In addition , there were no significant within- or between-group differences for change in NEEx . However , activity counts per minute were significantly higher ( P < 0.001 ) in the 600-kcal-per-session group ( 346 ± 141 min·d ) versus controls ( 290 ± 106 min·d ) at month 7 and significantly higher ( P < 0.001 ) in both the 600-kcal-per-session ( 345 ± 163 min·d ) and 400-kcal-per-session groups ( 317 ± 146 min·d ) versus controls ( 277 ± 116 min·d ) at 10 months . CONCLUSIONS A 10-month aerobic exercise training program in previously sedentary , overweight and obese young adults was not associated with compensatory decreases in NEEx or NEPA . Results suggest that overweight and obese individuals do not become less physically active or spend more time in sedentary pursuits in response to exercise Objective This study determined whether adding a self-regulatory intervention ( SRI ) focused on self-monitoring of spontaneous physical activity and sedentary behavior to a st and ard weight loss intervention improved maintenance of lost weight . Design and Methods Older ( 65–79 yrs ) , obese ( BMI = 30–40 kg/m2 ) adults ( n=48 ) were r and omized to a five-month weight loss intervention involving a hypocaloric diet ( DIET ) and aerobic exercise ( EX ) with or without the SRI to promote spontaneous physical activity and decrease sedentary behavior ( SRI+DIET+EX compared to DIET+EX ) . Following the weight loss phase , both groups transitioned to self-selected diet and exercise behavior during a 5-month follow-up . Throughout the 10-months , the SRI+DIET+EX group utilized real-time accelerometer feedback for self-monitoring . Results There was an overall group by time effect of the SRI ( P < 0.01 ) ; DIET+EX lost less weight and regained more weight than SRI+DIET+EX . The average weight regain during follow-up was 1.3 kg less in the SRI+DIET+EX group . Individuals in this group maintained ~10 % lower weight than baseline compared to those in the DIET+EX group whom maintained ~5 % lower weight than baseline . Conclusions Addition of a self-regulatory intervention , design ed to increase spontaneous physical activity and decrease sedentary behavior , to a st and ard weight loss intervention enhances successful maintenance of lost weight BACKGROUND Individuals may compensate for exercise training by modifying nonexercise behavior ( ie , increase sedentary time ( ST ) and decrease nonexercise physical activity [ NEPA ] ) . PURPOSE To compare ST and NEPA during a 12-week exercise training and /or lifestyle intervention . METHODS Fifty-seven overweight/obese participants ( 19 M/39 F ) completed the study ( mean ± SD ; age 43.6 ± 9.9 y , BMI 35.1 ± 4.6 kg/m2 ) . There were no between-group differences in activity levels at baseline . Four-arm quasi-experimental intervention study 1 ) EX : exercise 5 days per week at a moderate intensity ( 40 % to 65 % VO2peak ) 2 ) rST : reduce ST and increase NEPA , 3 ) EX-rST : combination of EX and rST and 4 ) CON : maintain habitual behavior . RESULTS For the EX group , ST did not decrease significantly ( mean ( ( 95 % confidence interval ) 0.48 ( -2.2 to 3.1)% and there was no changes in NEPA at week-12 compared with baseline . The changes were variable , with approximately 50 % of participants increasing ST and decreasing NEPA . The rST group decreased ST ( -4.8 ( 0.8 to 7.9)% and increased NEPA . EX-rST significantly decreased ST ( -5.1 ( -2.2 to 7.9)% and increased time in NEPA at week-12 compared with baseline . The control group increased ST by 4.3 ( 0.8 to 7.9)% . CONCLUSIONS Changes in nonexercise ST and NEPA are variable among participants in an exercise-training program , with nearly half decreasing NEPA compared with baseline . Interventions targeting multiple behaviors ( ST and NEPA ) may effectively reduce compensation and increase daily activity Objective : While there is a dose-response relationship between physical activity ( PA ) and health benefit , little is known about the effectiveness of different PA prescriptions on total daily PA . Aim : To test , under real-life conditions and using an objective , non-invasive measurement technique ( accelerometry ) , the effect of prescribing additional physical activity ( walking only ) of different duration s ( 30 , 60 and 90 min/day ) on compliance ( to the activity prescribed ) and compensation ( to total daily PA ) . Participants in each group were prescribed 5 sessions of walking per week over 4 weeks . Methods : 55 normal-weight and overweight women ( mean BMI 25 ± 5 kg/m2 , height 165 ± 1 cm , weight 68 ± 2 kg and mean age 27 ± 1 years ) were r and omly assigned to 3 prescription groups : 30 , 60 or 90 min/day PA . Results : Walking duration result ed in an almost linear increase in the number of steps per day during the prescription period from an average of about 10,000 steps per day for the 30-min prescription to about 14,000 for the 90-min prescription . Compliance was excellent for the 30-min prescription but decreased significantly with 60-min and 90-min prescriptions . In parallel , degree of compensation subsequent to exercise increased progressively as length of prescription increased . Conclusion : A 30-min prescription of extra walking 5 times per week was well tolerated . However , in order to increase total PA further , much more than 60 min of walking may need to be prescribed in the majority of individuals . While total exercise ‘ volume ' increased with prescriptions longer than 30 min , compliance to the prescription decreased and greater compensation was evident OBJECTIVE To determine what effect diet-induced approximately 12 kg weight loss in combination with exercise training has on body composition and resting energy expenditure ( REE ) in premenopausal African-American ( AA ) and European-American ( EA ) women . METHODS AND PROCEDURES This study was a longitudinal , r and omized weight loss clinical intervention , with either aerobic ( AT ) , resistance ( RT ) , or no exercise training ( NT ) . Forty-eight AA and forty-six EA premenopausal overweight ( BMI between 27 and 30 ) women underwent weight loss to a BMI < 25 . Body composition ( densitometry ) , REE ( indirect calorimetry ) , maximal oxygen uptake ( VO2max ) , and muscular strength ( isometric elbow flexion ) were evaluated when subjects were in energy balance . RESULTS AA women lost less fat-free mass ( FFM , P < or=0.05 ) ( 47.0+/-4.6 to 46.9+/-5.0 kg ) than EA women ( 46.4+/-4.9 to 45.2+/-4.6 kg ) . Regardless of race , RT maintained FFM ( P < or=0.05 ) following weight loss ( 46.9+/-5.2 to 47.2+/-5.0 kg ) whereas AT ( 45.4+/-4.2 to 44.4+/-4.1 kg ) and NT ( 47.9+/-4.7 to 46.4+/-5.1 kg ) decreased FFM ( P < or=0.05 ) . Both AT and NT decreased in REE with weight loss but RT did not . Significant time by group interactions ( all P < or=0.05 ) for strength indicated that RT maintained strength and AT did not . DISCUSSION AA women lost less FFM than EA women during equivalent weight losses . However , following weight loss in both AA and EA , RT conserved FFM , REE , and strength fitness when compared to women who AT or did not train Activity energy expenditure ( AEE ) is the component of daily energy expenditure that is mainly influenced by the amount of physical activity ( PA ) and by the weight of the body displaced . This study aim ed at analyzing the effect of weight loss on PA and AEE . The body weight and PA of 66 overweight and obese subjects were measured at baseline and after 12 weeks of 67 % energy restriction . PA was measured using a tri-axial accelerometer for movement registration ( Tracmor ) and quantified in activity counts . Tracmor recordings were also processed using a classification algorithm to recognize 6 common activity types engaged in during the day . A doubly-labeled water vali date d equation based on Tracmor output was used to estimate AEE . After weight loss , body weight decreased by 13±4 % , daily activity counts augmented by 9 % ( 95 % CI : + 2 % , + 15 % ) , and this increase was weakly associated with the decrease in body weight ( R(2 ) = 7 % ; P<0.05 ) . After weight loss subjects were significantly ( P<0.05 ) less sedentary ( -26 min/d ) , and increased the time spent walking ( + 11 min/d ) and bicycling ( + 4 min/d ) . However , AEE decreased by 0.6±0.4 MJ/d after weight loss . On average , a 2-hour/day reduction of sedentary time by increasing ambulatory and generic activities was required to restore baseline levels of AEE . In conclusion , after weight loss PA increased but the related metabolic dem and did not offset the reduction in AEE due to the lower body weight . Promoting physical activity according to the extent of weight loss might increase successfulness of weight maintenance PURPOSE An active lifestyle is widely recognized as having a beneficial effect on cardiovascular health . However , no clear consensus exists as to whether exercise training increases overall physical activity energy expenditure ( PAEE ) or whether individuals participating in regular exercise compensate by reducing their off-exercise physical activity . The purpose of this study was to evaluate changes in PAEE in response to aerobic training ( AT ) , resistance training ( RT ) , or combined aerobic and resistance training ( AT/RT ) . METHODS Data are from 82 participants in the Studies of Targeted Risk Reduction Interventions through Defined Exercise-Aerobic Training versus Resistance Training study , a r and omized trial of overweight ( body mass index = 25 - 35 kg·m(-2 ) ) adults , in which participants were r and omized to receive 8 months of AT , RT , or AT/RT . All subjects completed a 4-month control period before r and omization . PAEE was measured using triaxial RT3 accelerometers , which subjects wore for a 5- to 7-d period before and after the exercise intervention . Data reduction was performed with a previously published computer-based algorithm . RESULTS There was no significant change in off-exercise PAEE in any of the exercise training groups . We observed a significant increase in total PAEE that included the exercise training , in both AT and AT/RT but not in RT . CONCLUSIONS Eight months of exercise training was not associated with a compensatory reduction in off-exercise physical activity , regardless of exercise modality . The absence of compensation is particularly notable for AT/RT subjects , who performed a larger volume of exercise than did AT or RT subjects . We believe that the extended duration of our exercise training program was the key factor in allowing subjects to reach a new steady-state level of physical activity within their daily lives We have recently reported that obese women r and omized to a low-carbohydrate diet lost more than twice as much weight as those following a low-fat diet over 6 months . The difference in weight loss was not explained by differences in energy intake because women on the two diets reported similar daily energy consumption . We hypothesized that chronic ingestion of a low-carbohydrate diet increases energy expenditure relative to a low-fat diet and that this accounts for the differential weight loss . To study this question , 50 healthy , moderately obese ( body mass index , 33.2 + /- 0.28 kg/m(2 ) ) women were r and omized to 4 months of an ad libitum low-carbohydrate diet or an energy-restricted , low-fat diet . Resting energy expenditure ( REE ) was measured by indirect calorimetry at baseline , 2 months , and 4 months . Physical activity was estimated by pedometers . The thermic effect of food ( TEF ) in response to low-fat and low-carbohydrate breakfasts was assessed over 5 h in a subset of subjects . Forty women completed the trial . The low-carbohydrate group lost more weight ( 9.79 + /- 0.71 vs. 6.14 + /- 0.91 kg ; P < 0.05 ) and more body fat ( 6.20 + /- 0.67 vs. 3.23 + /- 0.67 kg ; P < 0.05 ) than the low-fat group . There were no differences in energy intake between the diet groups as reported on 3-d food records at the conclusion of the study ( 1422 + /- 73 vs. 1530 + /- 102 kcal ; 5954 + /- 306 vs. 6406 + /- 427 kJ ) . Mean REE in the two groups was comparable at baseline , decreased with weight loss , and did not differ at 2 or 4 months . The low-fat meal caused a greater 5-h increase in TEF than did the low-carbohydrate meal ( 53 + /- 9 vs. 31 + /- 5 kcal ; 222 + /- 38 vs. 130 + /- 21 kJ ; P = 0.017 ) . Estimates of physical activity were stable in the dieters during the study and did not differ between groups . These results confirm that short-term weight loss is greater in obese women on a low-carbohydrate diet than in those on a low-fat diet even when reported food intake is similar . The differential weight loss is not explained by differences in REE , TEF , or physical activity and likely reflects underreporting of food consumption by the low-fat dieters SUMMARY OBJECTIVE We investigated the relationship between the variability in body weight change among individuals and diet restriction or physical activity during a 14-week intervention . DESIGN A prospect i ve clinical trial with a 14-week weight reduction intervention design . In total , 90 middle aged , Japanese , obese women enrolled as subjects . MEASUREMENTS The outcome variable was the change in body weight during the intervention period . Other primary variables were total energy intake , carbohydrate intake , fat intake , protein intake , total energy expenditure ( TEE ) , and activity energy expenditure ( AEE ) . Diet intake was assessed by 3 days , weighed dietary records and dietary recall interviews . Physical activity was assessed by a uniaxial accelerometry sensor and a diary of exercise . RESULTS Significant reductions were observed in body weight ( -8.5 kg ) as a result of intervention . When the subjects were assigned to three categories depending on AEE during intervention , the loss of body weight was significantly greater for subjects within the upper ( -9.6 kg ) AEE category than for those in the middle ( -8.5 kg ) or lower AEE ( -7.5 kg ) categories . In addition , a significant correlation ( r = 0.57 , p < 0.0001 ) was observed between a subject 's AEE before and during the intervention . On the other h and , no significant correlation was observed between body weight reduction and energy intake , indicating that strict diet restriction does not always result in a large weight loss . CONCLUSION Activity energy expenditure , not only through voluntary exercise but also through spontaneous , daily , physical activities can have a positive effect on reducing body weight OBJECTIVE To compare energy intake , total daily energy expenditure ( TDEE ) , nonexercise energy expenditure ( NEEx ) , resting metabolic rate ( RMR ) , nonexercise physical activity ( NEPA ) , and sedentary time between participants with weight loss < 5 % ( nonresponders ) vs. ≥5 % ( responders ) in response to exercise . METHODS Adults ( 18 - 30 years ) with overweight/obesity ( BMI 25 - 40 kg/m(2 ) ) were r and omized to exercise : 5 days/week , 400 or 600 kcal/session , 10 months . RESULTS Of the participants , 40 responded and 34 did not respond to the exercise protocol . Nonresponder energy intake was higher vs. responders , significant only in men ( P=0.034 ) . TDEE increased only in responders ( P=0.001 ) . NEEx increased in responders and decreased in nonresponders , significant only in men ( P=0.045 ) . There were no within- or between-group differences for change in RMR . NEPA increased in responders and decreased in nonresponders ( group-by-time interactions : total sample , P=0.049 ; men , P=0.016 ) . Sedentary time decreased in both groups , significant only in men . CONCLUSIONS Men who did not lose weight in response to exercise ( < 5 % ) had higher energy intake and lower NEEx when compared with men losing ≥5 % . No significant differences in any parameters assessed were observed between women who lost < 5 % vs. those losing ≥5 % . Factors associated with the weight loss response to exercise in women warrant additional investigation BACKGROUND The Cochrane Collaboration is strongly encouraging the use of a newly developed tool , the Cochrane Collaboration Risk of Bias Tool ( CCRBT ) , for all review groups . However , the psychometric properties of this tool to date have yet to be described . Thus , the objective of this study was to add information about psychometric properties of the CCRBT including inter-rater reliability and concurrent validity , in comparison with the Effective Public Health Practice Project Quality Assessment Tool ( EPHPP ) . METHODS Both tools were used to assess the method ological quality of 20 r and omized controlled trials included in our systematic review of the effectiveness of knowledge translation interventions to improve the management of cancer pain . Each study assessment was completed independently by two review ers using each tool . We analysed the inter-rater reliability of each tool 's individual domains , as well as final grade assigned to each study . RESULTS The EPHPP had fair inter-rater agreement for individual domains and excellent agreement for the final grade . In contrast , the CCRBT had slight inter-rater agreement for individual domains and fair inter-rater agreement for final grade . Of interest , no agreement between the two tools was evident in their final grade assigned to each study . Although both tools were developed to assess ' quality of the evidence ' , they appear to measure different constructs . CONCLUSIONS Both tools performed quite differently when evaluating the risk of bias or method ological quality of studies in knowledge translation interventions for cancer pain . The newly introduced CCRBT assigned these studies a higher risk of bias . Its psychometric properties need to be more thoroughly vali date d , in a range of research fields , to underst and fully how to interpret results from its application INTRODUCTION We examined the effects of three exercise training interventions on total physical activity energy expenditure ( PAEE ) or nonexercise PAEE in a r and omized controlled trial where sedentary , overweight , and obese men and women were assigned to inactive control , low-amount/moderate-intensity , low-amount/vigorous-intensity , or high-amount/vigorous-intensity aerobic exercise . METHODS To measure PAEE , triaxial RT3 accelerometers were worn by subjects for 7 d at the beginning and end of an 8-month exercise intervention . In total , 50 subjects ( control , n = 8 ; two low-amount groups , n = 28 ; high-amount group , n = 14 ) had usable PAEE data collected at both time points . RESULTS At baseline , subjects had an average age of 53.2 yr , had a body mass index of 29.7 kg x m(-2 ) , and a relative peak VO2 of 28.7 mL x kg(-1 ) x min(-1 ) . There were no significant differences between groups at baseline . After the intervention , average change in total PAEE was 8.4 + /- 20.9 kJ x h(-1 ) for controls , 58.6 + /- 20.9 kJ x h(-1 ) for the two low-amount groups , and 138.1 + /- 33.5 kJ x h(-1 ) for the high-amount group ( means + /- SE ) . The high-amount group experienced a significantly greater increase in total PAEE compared with the controls ( P = 0.02 ) . As expected , total PAEE increased with increasing exercise volume . Average change in nonexercise PAEE was 8.4 + /- 20.9 kJ x h(-1 ) for control , 25.1 + /- 20.9 kJ x h(-1 ) for the low-amount groups combined , and 62.8 + /- 29.3 kJ x h(-1 ) for the high-amount group . There was no statistically significant difference in change of nonexercise PAEE among groups . CONCLUSIONS We conclude that in middle-aged overweight or obese subjects participating in an extended exercise intervention , total PAEE increased , and there was no compensatory decrease in nonexercise PAEE BACKGROUND No current treatment for obesity reliably sustains weight loss , perhaps because compensatory metabolic processes resist the maintenance of the altered body weight . We examined the effects of experimental perturbations of body weight on energy expenditure to determine whether they lead to metabolic changes and whether obese subjects and those who have never been obese respond similarly . METHODS We repeatedly measured 24-hour total energy expenditure , resting and nonresting energy expenditure , and the thermic effect of feeding in 18 obese subjects and 23 subjects who had never been obese . The subjects were studied at their usual body weight and after losing 10 to 20 percent of their body weight by underfeeding or gaining 10 percent by overfeeding . RESULTS Maintenance of a body weight at a level 10 percent or more below the initial weight was associated with a mean ( + /- SD ) reduction in total energy expenditure of 6 + /- 3 kcal per kilogram of fat-free mass per day in the subjects who had never been obese ( P < 0.001 ) and 8 + /- 5 kcal per kilogram per day in the obese subjects ( P < 0.001 ) . Resting energy expenditure and nonresting energy expenditure each decreased 3 to 4 kcal per kilogram of fat-free mass per day in both groups of subjects . Maintenance of body weight at a level 10 percent above the usual weight was associated with an increase in total energy expenditure of 9 + /- 7 kcal per kilogram of fat-free mass per day in the subjects who had never been obese ( P < 0.001 ) and 8 + /- 4 kcal per kilogram per day in the obese subjects ( P < 0.001 ) . The thermic effect of feeding and nonresting energy expenditure increased by approximately 1 to 2 and 8 to 9 kcal per kilogram of fat-free mass per day , respectively , after weight gain . These changes in energy expenditure were not related to the degree of adiposity or the sex of the subjects . CONCLUSIONS Maintenance of a reduced or elevated body weight is associated with compensatory changes in energy expenditure , which oppose the maintenance of a body weight that is different from the usual weight . These compensatory changes may account for the poor long-term efficacy of treatments for obesity The amount of weight loss induced by exercise is often disappointing . A diet-induced negative energy balance triggers compensatory mechanisms , e.g. , lower metabolic rate and increased appetite . However , knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited . A r and omized controlled trial was performed in healthy , sedentary , moderately overweight young men to examine the effects of increasing doses of aerobic exercise on body composition , accumulated energy balance , and the degree of compensation . Eighteen participants were r and omized to a continuous sedentary control group , 21 to a moderate-exercise ( MOD ; 300 kcal/day ) , and 22 to a high-exercise ( HIGH ; 600 kcal/day ) group for 13 wk , corresponding to ∼30 and 60 min of daily aerobic exercise , respectively . Body weight ( MOD : -3.6 kg , P < 0.001 ; HIGH : -2.7 kg , P = 0.01 ) and fat mass ( MOD : -4.0 kg , P < 0.001 and HIGH : -3.8 kg , P < 0.001 ) decreased similarly in both exercise groups . Although the exercise-induced energy expenditure in HIGH was twice that of MOD , the result ing accumulated energy balance , calculated from changes in body composition , was not different ( MOD : -39.6 Mcal , HIGH : -34.3 Mcal , not significant ) . Energy balance was 83 % more negative than expected in MOD , while it was 20 % less negative than expected in HIGH . No statistically significant changes were found in energy intake or nonexercise physical activity that could explain the different compensatory responses associated with 30 vs. 60 min of daily aerobic exercise . In conclusion , a similar body fat loss was obtained regardless of exercise dose . A moderate dose of exercise induced a markedly greater than expected negative energy balance , while a higher dose induced a small but quantifiable degree of compensation BACKGROUND Exercise interventions elicit only modest weight loss , which might reflect a compensatory reduction in nonprescribed physical activity energy expenditure ( PAEE ) . OBJECTIVE The objective was to investigate whether there is a reduction in nonprescribed PAEE as a result of participation in a 6-mo structured exercise intervention in middle-aged men . DESIGN Sedentary male participants [ age : 54 ± 5 y ; body mass index ( in kg/m² ) : 28 ± 3 ] were r and omly assigned to a 6-mo progressive exercise ( EX ) or control ( CON ) group . Energy expenditure during structured exercise ( prescribed PAEE ) and nonprescribed PAEE were determined with the use of synchronized accelerometry and heart rate before the intervention , during the intervention ( 2 , 9 , and 18 wk ) , and within a 2-wk period of detraining after the intervention . RESULTS Structured prescribed exercise increased total PAEE and had no detrimental effect on nonprescribed PAEE . Indeed , there was a trend for greater nonprescribed PAEE in the EX group ( P = 0.09 ) . Weight loss in the EX group ( -1.8 ± 2.2 kg compared with + 0.2 ± 2.2 kg in the CON group , P < 0.02 ) reflected only ≈40 % of the 300 - 373 kcal/kg body mass potential energy deficit from prescribed exercise . Serum leptin concentration decreased by 24 % in the EX group ( compared with 3 % in the CON group , P < 0.03 ) , and we estimate that this was accompanied by a compensatory increase in energy intake of ≈100 kcal/d . CONCLUSIONS The adoption of regular structured exercise in previously sedentary , middle-aged , and overweight men does not result in a negative compensatory reduction in nonprescribed physical activity . The less-than-predicted weight loss is likely to reflect a compensatory increase in energy intake in response to a perceived state of relative energy insufficiency |
12,873 | 30,522,529 | Key facilitators of integrated academic and health curricula were supportive senior management and alignment of the intervention with school ethos ; a positive teaching environment , including positive perceptions around the ability to be flexible in the adaptation and delivery of integrated academic and health curricula ; positive pre-existing student and teacher attitudes towards intervention content ; and parental support of interventions , largely through reinforcement of messaging at home .
Important barriers were over-burdened teachers , with little time to learn and implement integrated curricula .
ConclusionS everal useful facilitating and inhibiting factors linked to the implementation of interventions that integrate academic and health education for reduced substance use and /or violence were identified , providing tentative but insightful evidence of context -specific issues that may impact intervention success . | Background Within increasingly constrained school timetables , interventions that integrate academic and health education to reduce substance use and violence may hold promise as a category of intervention that can positively affect both academic and health outcomes .
There are no current systematic review s exploring the effectiveness of such interventions or factors that affect their implementation . | The integration of realist evaluation principles within r and omised controlled trials ( ‘ realist RCTs ’ ) enables evaluations of complex interventions to answer questions about what works , for whom and under what circumstances . This allows evaluators to better develop and refine mid-level programme theories . However , this is only one phase in the process of developing and evaluating complex interventions . We describe and exemplify how social scientists can integrate realist principles across all phases of the Medical Research Council framework . Intervention development , modelling , and feasibility and pilot studies need to theorise the context ual conditions necessary for intervention mechanisms to be activated . Where interventions are scaled up and translated into routine practice , realist principles also have much to offer in facilitating knowledge about longer-term sustainability , benefits and harms . Integrating a realist approach across all phases of complex intervention science is vital for considering the feasibility and likely effects of interventions for different localities and population subgroups Steps to Respect : A Bullying Prevention Program ( STR ) relies on a social – ecological model of prevention to increase school staff awareness and responsiveness , foster socially responsible beliefs among students , and teach social – emotional skills to students to reduce bullying behavior . As part of a school-r and omized controlled trial of STR , we examined predictors and outcomes associated with classroom curriculum implementation in intervention schools . Data on classroom implementation ( adherence and engagement ) were collected from a sample of teachers using a weekly on-line Teacher Implementation Checklist system . Pre-post data related to school bullying-related outcomes were collected from 1,424 students and archival school demographic data were obtained from the National Center for Education Statistics . Results of multilevel analyses indicated that higher levels of program engagement were influenced by school-level percentage of students receiving free/reduced lunch , as well as classroom-level climate indicators . Results also suggest that higher levels of program engagement were related to lower levels of school bullying problems , enhanced school climate and attitudes less supportive of bullying . Predictors and outcomes related to program fidelity ( i.e. , adherence ) were largely nonsignificant . Results suggest that student engagement is a key element of program impact , though implementation is influenced by both school-level demographics and classroom context R and omized trials of complex public health interventions generally aim to identify what works , accrediting specific intervention ' products ' as effective . This approach often fails to give sufficient consideration to how intervention components interact with each other and with local context . ' Realists ' argue that trials misunderst and the scientific method , offer only a ' successionist ' approach to causation , which brackets out the complexity of social causation , and fail to ask which interventions work , for whom and under what circumstances . We counter-argue that trials are useful in evaluating social interventions because r and omized control groups actually take proper account of rather than bracket out the complexity of social causation . Nonetheless , realists are right to stress underst and ing of ' what works , for whom and under what circumstances ' and to argue for the importance of theorizing and empirically examining underlying mechanisms . We propose that these aims can be ( and sometimes already are ) examined within r and omized trials . Such ' realist ' trials should aim to : examine the effects of intervention components separately and in combination , for example using multi-arm studies and factorial trials ; explore mechanisms of change , for example analysing how pathway variables mediate intervention effects ; use multiple trials across context s to test how intervention effects vary with context ; draw on complementary qualitative and quantitative data ; and be oriented towards building and validating ' mid-level ' program theories which would set out how interventions interact with context to produce outcomes . This last suggestion resonates with recent suggestions that , in delivering truly ' complex ' interventions , fidelity is important not so much in terms of precise activities but , rather , key intervention ' processes ' and ' functions ' . Realist trials would additionally determine the validity of program theory rather than only examining ' what works ' to better inform policy and practice in the long-term Organizational climate has been proposed as a factor that might influence a school ’s readiness to successfully implement school-wide prevention programs . The aim of this study was to evaluate the influence of teachers ’ perceptions of three dimensions of school organizational climate on the dosage and quality of teacher implementation of Positive Action , a social-emotional and character development ( SECD ) program . The dimensions measured were teachers ’ perceptions of ( a ) the school ’s openness to innovation , ( b ) the extent to which schools utilize participatory decision-making practice s , and ( c ) the existence of supportive relationships among teachers ( teacher-teacher affiliation ) . Data from 46 teachers in seven schools enrolled in the treatment arm of a longitudinal , cluster-r and omized , controlled trial were analyzed . Teacher perceptions of a school ’s tendency to be innovative was associated with a greater number of lessons taught and self-reported quality of delivery , and teacher-teacher affiliation was associated with a higher use of supplementary activities . The findings suggest that perceptions of a school ’s organizational climate impact teachers ’ implementation of SECD programs and have implication s for school administrators and technical assistance providers as they work to implement and sustain prevention programs in schools The Gatehouse Project is an innovative , comprehensive approach to mental health promotion in secondary schools . It sets out to promote student engagement and school connectedness as the way to improve emotional well-being and learning outcomes . The key elements of the whole-school intervention are the establishment and support of a school-based adolescent health team ; the identification of risk and protective factors in each school ’s social and leaning environment from student surveys ; and , through the use of these data , the identification and implementation of effective strategies to address these issues . The project evaluation used a cluster-r and omized controlled trial design involving 26 schools with initial results demonstrating considerable success in reducing smoking rates among Year 8 children . This article describes and accounts for how system-level changes have been made in schools through a process of capacity building . This encourages teachers , parents , and students to view the core business of education differently |
12,874 | 31,132,836 | However , NPI were not effective in reducing agitation , anxiety , or overall , or improving cognitive function .
Albeit the number of studies was limited , NPI improved ADL and depression in PWMSD | OBJECTIVE Due to limited efficacy of medications , non-pharmacological interventions ( NPI ) are frequently co-administered to people with moderate to severe dementia ( PWMSD ) .
This systematic review and meta- analysis investigated the effects of NPI on activities of daily living ( ADL ) , behavioral and psychological symptoms of dementia ( BPSD ) , and cognition and quality of life ( QoL ) of PWMSD . | BACKGROUND Several studies on the effect of physical exercise on activities of daily living ( ADL ) for people with dementia exist ; yet , data concerning the specific context of acute psychiatric hospitals remain scant . This study measured the effect of a physical exercise program on ADL scores in patients with moderate to severe dementia hospitalized in an acute psychiatric ward . METHODS A multicenter clinical trial was conducted in five Swiss and Belgian psychiatric hospitals . Participants were r and omly allocated to either an experimental group ( EG ) or a control group ( CG ) . Members of the EG received 20 physical exercise sessions ( strengthening , balance , and walking ) over a four-week period while members of the CG participated in social interaction sessions of equivalent duration and frequency , but without physical exercise . The effect of exercise on ADL was measured by comparing scores of the Barthel Index and the Functional Independence Measure in the EG and CG before and after the intervention , and two weeks later . RESULTS Hundred and sixty patients completed the program . Characteristics of participants of both groups were similar at the inception of the study . The mean ADL score of EG decreased slightly over time , whereas that of the CG significantly decreased compared to initial scores . Overall differences between groups were not significant ; however , significant differences were found for mobility-related items . CONCLUSIONS ADL scores in elderly with moderate to severe dementia deteriorate during acute psychiatric hospitalization . An exercise program delays the loss of mobility but does not have a significant impact on overall ADL scores 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 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 Neuropsychiatric Inventory ( NPI ) is a vali date d clinical instrument for evaluating psychopathology in dementia . The authors developed a brief question naire form of the NPI ( NPI-Q ) , intended for use in routine clinical practice , and cross-vali date d it with the NPI in 60 Alzheimer 's patients . Test-retest reliability of the NPI-Q was acceptable . The prevalence of analogous symptoms reported on the NPI and NPI-Q differed on average by 5 % ; moderate or severe symptom ratings differed by less than 2 % . The NPI-Q provides a brief , reliable , informant-based assessment of neuropsychiatric symptoms and associated caregiver distress that may be suitable for use in general clinical practice Abstract Objectives To determine the respective efficacy of quetiapine and rivastigmine for agitation in people with dementia in institutional care and to evaluate these treatments with respect to change in cognitive performance . Design R and omised double blind ( clinician , patient , outcomes assessor ) placebo controlled trial . Setting Care facilities in the north east of Engl and . Participants 93 patients with Alzheimer 's disease , dementia , and clinical ly significant agitation . Intervention Atypical antipsychotic ( quetiapine ) , cholinesterase inhibitor ( rivastigmine ) , or placebo ( double dummy ) . Main outcome measures Agitation ( Cohen-Mansfield agitation inventory ) and cognition ( severe impairment battery ) at baseline and at six weeks and 26 weeks . The primary outcome was agitation inventory at six weeks . Results 31 patients were r and omised to each group , and 80 ( 86 % ) started treatment ( 25 rivastigmine , 26 quetiapine , 29 placebo ) , of whom 71 ( 89 % ) tolerated the maximum protocol dose ( 22 rivastigmine , 23 quetiapine , 26 placebo ) . Compared with placebo , neither group showed significant differences in improvement on the agitation inventory either at six weeks or 26 weeks . Fifty six patients scored > 10 on the severe impairment battery at baseline , 46 ( 82 % ) of whom were included in the analysis at six week follow up ( 14 rivastigmine , 14 quetiapine , 18 placebo ) . For quetiapine the change in severe impairment battery score from baseline was estimated as an average of -14.6 points ( 95 % confidence interval -25.3 to -4.0 ) lower ( that is , worse ) than in the placebo group at six weeks ( P = 0.009 ) and -15.4 points ( -27.0 to -3.8 ) lower at 26 weeks ( P = 0.01 ) . The corresponding changes with rivastigmine were -3.5 points ( -13.1 to 6.2 ) lower at six weeks ( P = 0.5 ) and -7.5 points ( -21.0 to 6.0 ) lower at 26 weeks ( P = 0.3 ) . Conclusions Neither quetiapine nor rivastigmine are effective in the treatment of agitation in people with dementia in institutional care . Compared with placebo , quetiapine is associated with significantly greater cognitive decline Objective : To determine whether an activity specific exercise program could improve ability to perform basic mobility activities in long-term care residents with Alzheimer disease ( AD ) . Design : R and omized , controlled , single-blinded clinical trial . Setting : Residents of 7 long-term care facilities . Participants : Eighty-two long-term care residents with mild to severe AD . Intervention : An activity specific exercise program was compared to a walking program and to an attention control . Measurements : Ability to perform bed mobility and transfers was assessed using the subscales of the Acute Care Index of Function ; functional mobility was measured using the 6-Minute Walk test . Results : Subjects receiving the activity specific exercise program improved in ability to perform transfers , whereas subjects in the other 2 groups declined CONTEXT Memantine is a low- to moderate-affinity , uncompetitive N-methyl-D-aspartate receptor antagonist . Controlled trials have demonstrated the safety and efficacy of memantine monotherapy for patients with moderate to severe Alzheimer disease ( AD ) but no controlled trials of memantine in patients receiving a cholinesterase inhibitor have been performed . OBJECTIVE To compare the efficacy and safety of memantine vs placebo in patients with moderate to severe AD already receiving stable treatment with donepezil . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled clinical trial of 404 patients with moderate to severe AD and Mini-Mental State Examination scores of 5 to 14 , who received stable doses of donepezil , conducted at 37 US sites between June 11 , 2001 , and June 3 , 2002 . A total of 322 patients ( 80 % ) completed the trial . INTERVENTIONS Participants were r and omized to receive memantine ( starting dose 5 mg/d , increased to 20 mg/d , n = 203 ) or placebo ( n = 201 ) for 24 weeks . MAIN OUTCOME MEASURES Change from baseline on the Severe Impairment Battery ( SIB ) , a measure of cognition , and on a modified 19-item AD Cooperative Study -Activities of Daily Living Inventory ( ADCS-ADL19 ) . Secondary outcomes included a Clinician 's Interview-Based Impression of Change Plus Caregiver Input ( CIBIC-Plus ) , the Neuropsychiatric Inventory , and the Behavioral Rating Scale for Geriatric Patients ( BGP Care Dependency Subscale ) . RESULTS The change in total mean ( SE ) scores favored memantine vs placebo treatment for SIB ( possible score range , 0 - 100 ) , 0.9 ( 0.67 ) vs -2.5 ( 0.69 ) , respectively ( P<.001 ) ; ADCS-ADL19 ( possible score range , 0 - 54 ) , -2.0 ( 0.50 ) vs -3.4 ( 0.51 ) , respectively ( P = .03 ) ; and the CIBIC-Plus ( possible score range , 1 - 7 ) , 4.41 ( 0.074 ) vs 4.66 ( 0.075 ) , respectively ( P = .03 ) . All other secondary measures showed significant benefits of memantine treatment . Treatment discontinuations because of adverse events for memantine vs placebo were 15 ( 7.4 % ) vs 25 ( 12.4 % ) , respectively . CONCLUSIONS In patients with moderate to severe AD receiving stable doses of donepezil , memantine result ed in significantly better outcomes than placebo on measures of cognition , activities of daily living , global outcome , and behavior and was well tolerated . These results , together with previous studies , suggest that memantine represents a new approach for the treatment of patients with moderate to severe AD Objectives To investigate the effects of a high-intensity functional exercise program on independence in activities of daily living ( ADLs ) and balance in older people with dementia and whether exercise effects differed between dementia types . Design Cluster-r and omized controlled trial : Umeå Dementia and Exercise ( UMDEX ) study . Setting Residential care facilities , Umeå , Sweden . Participants Individuals aged 65 and older with a dementia diagnosis , a Mini-Mental State Examination score of 10 or greater , and dependence in ADLs ( N = 186 ) . Intervention Ninety-three participants each were allocated to the high-intensity functional exercise program , comprising lower limb strength and balance exercises , and 93 to a seated control activity . Measurements Blinded assessors measured ADL independence using the Functional Independence Measure ( FIM ) and Barthel Index ( BI ) and balance using the Berg Balance Scale ( BBS ) at baseline and 4 ( directly after intervention completion ) and 7 months . Results Linear mixed models showed no between-group effect on ADL independence at 4 ( FIM=1.3 , 95 % confidence interval (CI)=−1.6–4.3 ; BI=0.6 , 95 % CI=−0.2–1.4 ) or 7 ( FIM=0.8 , 95 % CI=−2.2–3.8 ; BI=0.6 , 95 % CI=−0.3–1.4 ) months . A significant between-group effect on balance favoring exercise was observed at 4 months ( BBS=4.2 , 95 % CI=1.8–6.6 ) . In interaction analyses , exercise effects differed significantly between dementia types . Positive between-group exercise effects were found in participants with non-Alzheimer 's dementia according to the FIM at 7 months and BI and BBS at 4 and 7 months . Conclusion In older people with mild to moderate dementia living in residential care facilities , a 4-month high-intensity functional exercise program appears to slow decline in ADL independence and improve balance , albeit only in participants with non-Alzheimer 's dementia BACKGROUND Although there is good evidence that interventions for carers of people with Alzheimer 's disease can reduce stress , no systematic studies have investigated psychotherapeutic intervention for patients themselves . This may be important in the earlier stages of Alzheimer 's disease , where insight is often preserved . AIMS The aim was to assess , in a r and omised controlled trial , whether psychotherapeutic intervention could benefit cognitive function , affective symptoms and global well-being . METHOD Individuals were r and omised to receive six sessions of psychodynamic interpersonal therapy or treatment as usual ; cognitive function , activities of daily living , a global measure of change , and carer stress and coping were assessed prior to and after the intervention . RESULTS No improvement was found on the majority of outcome measures . There was a suggestion that therapy had improved the carers ' reactions to some of the symptoms . CONCLUSIONS There is no evidence to support the widespread introduction of brief psychotherapeutic approaches for those with Alzheimer 's disease . However , the technique was acceptable and helpful individually 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 OBJECTIVE To develop a study Design Algorithm for Medical Literature on Intervention ( DAMI ) and test its interrater reliability , construct validity , and ease of use . STUDY DESIGN AND SETTING We developed and then revised the DAMI to include detailed instructions . To test the DAMI 's reliability , we used a purposive sample of 134 primary , mainly nonr and omized studies . We then compared the study design s as classified by the original authors and through the DAMI . Unweighted kappa statistics were computed to test interrater reliability and construct validity based on the level of agreement between the original and DAMI classifications . Assessment time was also recorded to evaluate ease of use . RESULTS The DAMI includes 13 study design s , including experimental and observational studies of interventions and exposure . Both the interrater reliability ( unweighted kappa = 0.67 ; 95 % CI [ 0.64 - 0.75 ] ) and construct validity ( unweighted kappa = 0.63 , 95 % CI [ 0.52 - 0.67 ] ) were substantial . Mean classification time using the DAMI was 4.08 ± 2.44 minutes ( range , 0.51 - 10.92 ) . CONCLUSIONS The DAMI showed substantial interrater reliability and construct validity . Furthermore , given its ease of use , it could be used to accurately classify medical literature for systematic review s of interventions although minimizing disagreement between authors of such review Although musical interventions have recently gained popularity as a non-pharmacological treatment in dementia , there is still insufficient evidence of their effectiveness . To investigate this issue , a single-center r and omized controlled trial was conducted with forty-eight patients with Alzheimer 's disease or mixed dementia to compare the effects of music versus cooking interventions in the emotional , cognitive , and behavioral domain , as well as on professional caregiver distress . Each intervention lasted four weeks ( two one-hour sessions a week ) . Multi-component evaluations ( with blind assessors ) were conducted before , during , and after the interventions to assess their short and long-term effects ( up to four weeks post interventions ) . Analyses revealed that both music and cooking interventions led to positive changes in the patients ' emotional state and decreased the severity of their behavioral disorders , as well as reduced caregiver distress . However , no benefit on the cognitive status of the patients was seen . While results did not demonstrate a specific benefit of music on any of the considered measures , the present study suggests the efficacy of two pleasant non-pharmacological treatments in patients with moderate to severe dementia . Our findings highlight the potential of such interventions in improving the well-being of patients living in residential care , as well as reducing caregiver distress Objective : To assess the effectiveness of ear acupressure and massage vs. control in the improvement of pain , anxiety and depression in persons diagnosed with dementia . Design : A pilot r and omized controlled trial . Setting : Residential homes in Extremadura ( Spain ) . Subjects : A total of 120 elders with dementia institutionalized in residential homes . Intervention : The participants were r and omly allocated , in three groups . Control group – they continued with their routine activities ; ear acupressure intervention group – they received ear acupressure treatment ( pressure was applied to acupressure points on the ear ) ; and massage therapy intervention group – they received relaxing massage therapy . Main measures : The variables pain , anxiety and depression were assessed with the Doloplus2 , Cornell and Campbell scales . The study was carried out during five months ; three months of experimental treatment and two months with no treatment . The assessment s were done at baseline , each month during the treatment and at one and two months of follow-up . In the statistical analysis the three groups were compared with each other . Results : A total of 111 participants completed the study . Their aged ranged from 67 to 91 years old and 86 of them ( 77.4 % ) were women . The ear acupressure intervention group showed better improvements than the massage therapy intervention group in relation to pain and depression during the treatment period and at one month of follow-up . The best improvement in pain was achieved in the last ( 3rd ) month of ear acupressure treatment ( p < 0.001 ) being the average improvement 8.55 ( 4.39 ) with IC 95 % ( 7.14 , 9.95 ) . Regarding anxiety , the best results were also observed in the last month of treatment . The average improvement in anxiety was 9.63 ( 5.00 ) with IC 95 % ( 8.02 , 11.23 ) Conclusions : Ear acupressure and massage therapy showed better results than the control group in relation to pain , anxiety and depression . However , ear acupressure achieved more improvements 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 : Between 75–90 % of nursing home ( NH ) residents with dementia develop behavioral symptoms ( BSD ) which may be associated with a stress response . Therapeutic touch has been shown to decrease restlessness in NH residents , however the mechanism is unknown . The purpose of this r and omized controlled trial ( RCT ) was to examine the effect of therapeutic touch on BSD and basal cortisol levels among NH residents with dementia . Participants and Methods : Using a double blind experimental interrupted time series ABAB design , 65 participants were assigned to one of three groups . The experimental group received therapeutic touch with contact on the neck and shoulders delivered twice daily for 3 days ( administered over 2 separate treatment periods ) ; the placebo group received a mimic treatment identical in appearance , and the control group received routine care . Study outcomes were BSD , measured by the modified Agitated Behavior Rating Scale ( mABRS ) , and salivary cortisol levels , measured by enzyme-linked immunosorbent assay ( ELISA ) . Results : 64 residents , aged 67–93 years ( M = 85.5 , SD = 5.50 ) , completed the study . Restlessness was significantly reduced in the experimental group compared to the control group ( p = 0.03 ) . There was a significant difference in morning cortisol variability among groups across time periods ( < 0.0001 ) . Findings suggest that therapeutic touch may be effective for management of symptoms like restlessness coupled with stress reduction . At a time when cost containment is a consideration in health care , therapeutic touch is an intervention that is non-invasive , readily learned , and can provide a non-pharmacologic alternative for selected persons with BSD OBJECTIVES To investigate the effectiveness of an exercise program in improving ability to perform activities of daily living ( ADLs ) , physical performance , and nutritional status and decreasing behavioral disturbance and depression in patients with Alzheimer 's disease ( AD ) . DESIGN R and omized , controlled trial . SETTING Five nursing homes . PARTICIPANTS One hundred thirty-four ambulatory patients with mild to severe AD . INTERVENTION Collective exercise program ( 1 hour , twice weekly of walk , strength , balance , and flexibility training ) or routine medical care for 12 months . MEASUREMENTS ADLs were assessed using the Katz Index of ADLs . Physical performance was evaluated using 6-meter walking speed , the get-up- and -go test , and the one-leg-balance test . Behavioral disturbance , depression , and nutritional status were evaluated using the Neuropsychiatric Inventory , the Montgomery and Asberg Depression Rating Scale , and the Mini-Nutritional Assessment . For each outcome measure , the mean change from baseline to 12 months was calculated using intention-to-treat analysis . RESULTS ADL mean change from baseline score for exercise program patients showed a slower decline than in patients receiving routine medical care ( 12-month mean treatment differences : ADL=0.39 , P=.02 ) . A significant difference between the groups in favor of the exercise program was observed for 6-meter walking speed at 12 months . No effect was observed for behavioral disturbance , depression , or nutritional assessment scores . In the intervention group , adherence to the program sessions in exploratory analysis predicted change in ability to perform ADLs . No adverse effects of exercise occurred . CONCLUSION A simple exercise program , 1 hour twice a week , led to significantly slower decline in ADL score in patients with AD living in a nursing home than routine medical care BACKGROUND Agitation is common in people with dementia , is distressing to patients and stressful to their carers . Drugs used to treat the condition have the potential to cause particularly severe side effects in older people with dementia and have been associated with an increased death rate . Alternatives to drug treatment for agitation should be sought . The study aim ed to assess the effects of bright light therapy on agitation and sleep in people with dementia . METHODS A single center r and omized controlled trial of bright light therapy versus st and ard light was carried out . The study was completed prior to the m and atory registration of r and omized controls on the clinical trials registry data base and , owing to delays in writing up , retrospective registration was not completed . RESULTS There was limited evidence of reduction in agitation in people on active treatment , sleep was improved and a suggestion of greater efficacy in the winter months . CONCLUSIONS Bright light therapy is a potential alternative to drug treatment in people with dementia who are agitated 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 Discussion | In this study of health care utilization data , use of amiodarone but not of other antiarrhythmic drugs was associated with a 50 % increased odds of acute pancreatitis among patients with NVAF . The odds were almost doubled in the 12 months after amiodarone therapy initiation and did not depend on cumulative use of amiodarone . Considering an incidence of acute pancreatitis of 3 to 4 cases per 10 000 adults per year,4 the observed association would result in approximately 1 to 2 additional cases of acute pancreatitis per 10 000 amiodarone users per year . A few isolated case reports of acute pancreatitis possibly linked to amiodarone use have been described in the literature .1 - 3 The mechanisms responsible for this association are unknown , although direct cytotoxicity or immune-mediated pathways , as described for amiodarone-related pulmonary toxic effects , could be potential explanations.5 Strengths of our study include the prospect i ve assessment of medication use , the large sample size , and the availability of information on comorbidities and use of other medications potentially associated with increased risk of acute pancreatitis . Limitations are related to the use of health care utilization data : limited information on the validity of cl aims for acute pancreatitis , absence of clinical variables that characterize severity of the episode ( eg , blood markers of acute pancreatitis ) , and the select group of patients included in this data base . Our results indicate that acute pancreatitis could be an adverse effect of amiodarone use , an effect that may not be shared by other antiarrhythmic drugs . Even though the absolute risk of acute pancreatitis in the general population is low , health care professionals should be aware of this potential association in the treatment of patients with NVAF or acute pancreatitis . Further research should replicate our findings and determine potential mechanisms |
12,875 | 29,462,179 | Our findings indicate that patient navigator programs improve processes of care , although few studies assessed patient experience , clinical outcomes or costs . | BACKGROUND People with chronic diseases experience barriers to managing their diseases and accessing available health services .
Patient navigator programs are increasingly being used to help people with chronic diseases navigate and access health services .
OBJECTIVE The objective of this review was to summarize the evidence for patient navigator programs in people with a broad range of chronic diseases , compared to usual care . | OBJECTIVES We conducted a trial to evaluate the effectiveness of a cervical cancer control intervention for Vietnamese American women that used lay health workers . METHODS The study group included 234 women who had not received a Papanicolaou ( Pap ) test in the last 3 years . Experimental group participants received a lay health worker home visit . Our trial endpoint was Pap test receipt within 6 months of r and omization . Pap testing completion was ascertained through women 's self-reports and medical record review s. We examined intervention effects among women who had ever received a Pap test ( prior to r and omization ) and women who had never received a Pap test . RESULTS Three quarters of the women in the experimental group completed a home visit . Ever-screened experimental group women were significantly more likely to report Pap testing ( P < .02 ) and to have records verifying Pap testing ( P < .04 ) than were ever-screened control group women . There were no significant differences between the trial arms for women who had never been screened . CONCLUSIONS Our findings indicate that lay health worker-based interventions for Vietnamese American women are feasible to implement and can increase levels of Pap testing use among ever-screened women but not among never-screened women Despite free colorectal cancer screening in France , participation remains low and low socioeconomic status is associated with a low participation . Our aim was to assess the effect of a screening navigation program on participation and the reduction in social inequalities in a national-level organized mass screening program for colorectal cancer by fecal-occult blood test ( FOBT ) . A multicenter ( 3 French departments ) cluster r and omized controlled trial was conducted over two years . The cluster was a small geographical unit stratified according to a deprivation index and the place of residence . A total of 14,556 subjects ( 72 clusters ) were included in the control arm where the FOBT program involved the usual postal reminders , and 14,373 subjects ( 66 clusters ) were included in the intervention arm . Intervention concerned only non-attended subjects with a phone number available defined as the navigable population . A screening navigator was added to the usual screening organization to identify and eliminate barriers to CRC screening with personalized contact . The participation rate by strata increased in the intervention arm . The increase was greater in affluent strata than in deprived ones . Multivariate analyses demonstrated that the intervention mainly with phone navigation increased individual participation ( OR=1.19 [ 1.10 , 1.29 ] ) in the navigable population . For such interventions to reduce social inequalities in a country with a national level organized mass screening program , they should first be administered to deprived population s , in accordance with the principle of proportionate universalism . Clinical Trials.gov Identifier : NCT01555450 IMPORTANCE Patient navigation ( PN ) to improve cancer screening in low-income and racial/ethnic minority population s usually focuses on navigating for single cancers in community health center setting s. OBJECTIVE We evaluated PN for breast , cervical , and colorectal cancer screening using a population -based information technology ( IT ) system within a primary care network . DESIGN , SETTING , AND PARTICIPANTS R and omized clinical trial conducted from April 2014 to December 2014 in 18 practice s in an academic primary care network . All patients eligible and overdue for cancer screening were identified and managed using a population -based IT system . Those at high risk for nonadherence with completing screening were identified using an electronic algorithm ( language spoken , number of overdue tests , no-show visit history ) , and r and omized to a PN intervention ( n = 792 ) or usual care ( n = 820 ) . Navigators used the IT system to track patients , contact them , and provide intense outreach to help them complete cancer screening . MAIN OUTCOMES AND MEASURES Mean cancer screening test completion rate over 8-month trial for each eligible patient , with all overdue cancer screening tests combined using linear regression models . Secondary outcomes included the proportion of patients completing any and each overdue cancer screening test . RESULTS Among 1612 patients ( 673 men and 975 women ; median age , 57 years ) , baseline patient characteristics were similar among r and omized groups . Of 792 intervention patients , patient navigators were unable to reach 151 ( 19 % ) , deferred 246 ( 38 % ) ( eg , patient declined , competing comorbidity ) , and navigated 202 ( 32 % ) . The mean proportion of patients who were up to date with screening among all overdue screening examinations was higher in the intervention vs the control group for all cancers combined ( 10.2 % vs 6.8 % ; 95 % CI [ for the difference ] , 1.5%-5.2 % ; P < .001 ) , and for breast ( 14.7 % vs 11.0 % ; 95 % CI , 0.2%-7.3 % ; P = .04 ) , cervical ( 11.1 % vs 5.7 % ; 95 % CI , 0.8%-5.2 % ; P = .002 ) , and colon ( 7.6 % vs 4.6 % ; 95 % CI , 0.8%-5.2 % ; P = .01 ) cancer compared with control . The proportion of overdue patients who completed any cancer screening during follow-up was higher in the intervention group ( 25.5 % vs 17.0 % ; 95 % CI , 4.7%-12.7 % ; P < .001 ) . The intervention group had more patients completing screening for breast ( 23.4 % vs 16.6 % ; 95 % CI , 1.8%-12.0 % ; P = .009 ) , cervical ( 14.4 % vs 8.6 % ; 95 % CI , 1.6%-10.5 % ; P = .007 ) , and colorectal ( 13.7 % vs 7.0 % ; 95 % CI , 3.2%-10.4 % ; P < .001 ) cancer . CONCLUSIONS AND RELEVANCE Patient navigation as part of a population -based IT system significantly increased screening rates for breast , cervical , and colorectal cancer in patients at high risk for nonadherence with testing . Integrating patient navigation into population health management activities for low-income and racial/ethnic minority patients might improve equity of cancer care . TRIAL REGISTRATION clinical trials.gov Identifier : NCT02553538 Imprisonment provides opportunities for the diagnosis and successful treatment of HIV , however , the benefits of antiretroviral therapy are frequently lost following release due to suboptimal access and utilization of health care and services . In response , some have advocated for development of intensive case-management interventions spanning incarceration and release to support treatment adherence and community re-entry for HIV-infected releasees . We conducted a r and omized controlled trial of a motivational Strengths Model bridging case management intervention ( BCM ) beginning approximately 3 months prior to and continuing 6 months after release versus a st and ard of care prison-administered discharge planning program ( SOC ) for HIV-infected state prison inmates . The primary outcome variable was self-reported access to post-release medical care . Of the 104 inmates enrolled , 89 had at least 1 post-release study visit . Of these , 65.1 % of BCM and 54.4 % of SOC assigned participants attended a routine medical appointment within 4 weeks of release ( P > 0.3 ) . By week 12 post-release , 88.4 % of the BCM arm and 78.3 % of the SOC arm had at attended at least one medical appointment ( P = 0.2 ) , increasing in both arms at week 24–90.7 % with BCM and 89.1 % with SOC ( P > 0.5 ) . No participant without a routine medical visit by week 24 attended an appointment from weeks 24 to 48 . The mean number of clinic visits during the 48 weeks post release was 5.23 ( SD = 3.14 ) for BCM and 4.07 ( SD = 3.20 ) for SOC ( P > 0.5 ) . There were no significant differences between arms in social service utilization and re-incarceration rates were also similar . We found that a case management intervention bridging incarceration and release was no more effective than a less intensive pre-release discharge planning program in supporting health and social service utilization for HIV-infected individuals released from prison OBJECTIVE To assess the impact of health coaching on patients ' in their primary care provider . METHODS R and omized controlled trial comparing health coaching with usual care . PARTICIPANTS Low-income English or Spanish speaking patients age 18 - 75 with poorly controlled type 2 diabetes , hypertension and /or hyperlipidemia . MAIN OUTCOME MEASURE Patient trust in their primary care provider measured by the 11-item Trust in Physician Scale , converted to a 0 - 100 scale . ANALYSIS Linear mixed modeling . RESULTS A total of 441 patients were r and omized to receive 12 months of health coaching ( n=224 ) vs. usual care ( n=217 ) . At baseline , the two groups were similar to those in the usual care group with respect to demographic characteristics and levels of trust in their provider . After 12 months , the mean trust level had increased more in patients receiving health coaching ( 3.9 vs. 1.5 , p=0.47 ) , this difference remained significant after adjustment for number of visits to primary care providers ( adjusted p=.03 ) . CONCLUSIONS Health coaching appears to increase patients trust in their primary care providers . PRACTICE IMPLICATION S Primary care providers should consider adding health coaches to their team as a way to enhance their relationship with their patients OBJECTIVES We compared the effectiveness of a telephone outreach approach versus a direct mail approach in improving rates of colorectal cancer ( CRC ) screening in a predominantly Black population . METHODS A r and omized trial was conducted between 2000 and 2003 that followed 456 participants in the New York metropolitan area who had not had recent CRC screening . The intervention group received tailored telephone outreach , and the control group received mailed printed material s. The primary outcome was medically documented CRC screening 6 months or less after r and omization . RESULTS CRC screening was documented in 61 of 226 ( 27.0 % ) intervention participants and in 14 of 230 ( 6.1 % ) controls ( prevalence rate difference=20.9 % ; 95 % CI = 14.34 , 27.46 ) . Compared with the control group , the intervention group was 4.4 times more likely to receive CRC screening within 6 months of r and omization . CONCLUSIONS Tailored telephone outreach can increase CRC screening in an urban minority population PURPOSE : Awareness of and enrollment in outpatient cardiac rehabilitation ( OCR ) following a cardiac event or procedure remain suboptimal . Thus , it is important to identify new approaches to improve these outcomes . The objectives of this study were to identify ( 1 ) the contributions of a patient navigation ( PN ) intervention and other patient characteristics on OCR awareness ; and ( 2 ) the contributions of OCR awareness and other patient characteristics on OCR enrollment among eligible cardiac patients up to 12 weeks posthospitalization . METHODS : In this r and omized controlled study , 181 eligible and consenting patients were assigned to either PN ( n = 90 ) or usual care ( UC ; n = 91 ) prior to hospital discharge . Awareness of OCR was assessed by telephone interview at 12 weeks posthospitalization , and OCR enrollment was confirmed by staff at collaborating OCR programs . Of the 181 study participants , 3 died within 1 month of hospital discharge and 147 completed the 12-week telephone interview . RESULTS : Participants in the PN intervention arm were nearly 6 times more likely to have at least some awareness of OCR than UC participants ( OR = 5.99 ; P = .001 ) . Moreover , participants who reported at least some OCR awareness were more than 9 times more likely to enroll in OCR ( OR = 9.27 , P = .034 ) and participants who were married were less likely to enroll ( P = .031 ) . CONCLUSIONS : Lay health advisors have potential to improve awareness of outpatient rehabilitation services among cardiac patients , which , in turn , can yield greater enrollment rates in a program BACKGROUND The study aim ed to determine the effect of preference-based tailored navigation on colorectal cancer ( CRC ) screening adherence and related outcomes among African Americans ( AAs ) . METHODS We conducted a r and omized controlled trial that included 764 AA patients who were age 50 to 75 years , were eligible for CRC screening , and had received care through primary care practice s in Philadelphia . Consented patients completed a baseline telephone survey and were r and omized to either a St and ard Intervention ( SI ) group ( n = 380 ) or a Tailored Navigation Intervention ( TNI ) group ( n = 384 ) . The SI group received a mailed stool blood test kit plus colonoscopy instructions , and a reminder . The TNI group received tailored navigation ( a mailed stool blood test kit or colonoscopy instructions based on preference , plus telephone navigation ) and a reminder . A six-month survey and a 12-month medical records review were completed to assess screening adherence , change in overall screening preference , and perceptions about screening . Multivariable analyses were performed to assess intervention impact on outcomes . RESULTS At six months , adherence in the TNI group was statistically significantly higher than in the SI group ( OR = 2.1 , 95 % CI = 1.5 to 2.9 ) . Positive change in overall screening preference was also statistically significantly greater in the TNI group compared with the SI group ( OR = 1.5 , 95 % CI = 1.0 to 2.3 ) . There were no statistically significant differences in perceptions about screening between the study groups . CONCLUSIONS Tailored navigation in primary care is a promising approach for increasing CRC screening among AAs . Research is needed to determine how to maximize intervention effects and to test intervention impact on race-related disparities in mortality and survival Background : Prior r and omized , controlled trials ( RCTs ) indicate that patient navigation can boost colorectal cancer screening rates in primary care . The sparse literature on pragmatic trials of interventions design ed to increase colorectal cancer screening adherence motivated this trial on the impact of a patient navigation intervention that included support for performance of the participants ' preferred screening test ( colonoscopy or stool blood testing ) . Material s and Methods : Primary care patients ( n = 5,240 ) , 50 to 74 years of age , with no prior diagnosis of bowel cancer and no record of a recent colorectal cancer screening test , were identified at the Group Health Centre in northern Ontario . These patients were r and omly assigned to an intervention group ( n = 2,629 ) or a usual care control group ( n = 2,611 ) . Intervention group participants were contacted by a trained nurse navigator by telephone to discuss colorectal cancer screening . Interested patients met with the navigator , who helped them identify and arrange for performance of the preferred screening test . Control group participants received usual care . Multivariate analyses were conducted using medical records data to assess intervention impact on screening adherence within 12 months after r and omization . Results : Mean patient age was 59 years , and 50 % of participants were women . Colorectal cancer screening adherence was higher in the intervention group ( 35 % ) than in the control group ( 20 % ) , a difference that was statistically significant ( OR , 2.11 ; confidence interval , 1.87–2.39 ) . Conclusion : Preference-based patient navigation increased screening uptake in a pragmatic RCT . Impact : Patient navigation increased colorectal cancer screening rates in a pragmatic RCT in proportions similar to those observed in explanatory RCTs . Cancer Epidemiol Biomarkers Prev ; 24(3 ) ; 506–11 . © 2014 AACR BACKGROUND Patient navigators may increase colorectal cancer ( CRC ) screening rates among adults in underserved communities , but prior r and omized trials have been small or conducted at single sites and have not included substantial numbers of Haitian Creole-speaking or Portuguese-speaking patients . METHODS We identified 465 primary care patients from 4 community health centers and 2 public hospital-based clinics who were not up-to- date with CRC screening and spoke English , Haitian Creole , Portuguese , or Spanish as their primary language . We enrolled participants from September 1 , 2008 , through March 31 , 2009 , and followed them up for 1 year after enrollment . We r and omly allocated patients to receive a patient navigation-based intervention or usual care . Intervention patients received an introductory letter from their primary care provider with educational material , followed by telephone calls from a language -concordant navigator . The navigators offered patients the option of being screened by fecal occult blood testing or colonoscopy . The primary outcome was completion of any CRC screening within 1 year . Secondary outcomes included the proportions of patients screened by colonoscopy who had adenomas or cancer detected . RESULTS During a 1-year period , intervention patients were more likely to undergo CRC screening than control patients ( 33.6 % vs 20.0 % ; P < .001 ) , to be screened by colonoscopy ( 26.4 % vs 13.0 % ; P < .001 ) , and to have adenomas detected ( 8.1 % vs 3.9 % ; P = .06 ) . In prespecified subgroup analyses , the navigator intervention was particularly beneficial for patients whose primary language was other than English ( 39.8 % vs 18.6 % ; P < .001 ) and black patients ( 39.7 % vs 16.7 % ; P = .004 ) . CONCLUSIONS Patient navigation increased completion of CRC screening among ethnically diverse patients . Targeting patient navigation to black and non-English-speaking patients may be a useful approach to reducing disparities in CRC screening . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01141114 OBJECTIVES We tested the effectiveness of a culturally tailored , behavioral theory-based community health worker intervention for improving glycemic control . METHODS We used a r and omized , 6-month delayed control group design among 164 African American and Latino adult participants recruited from 2 health systems in Detroit , Michigan . Our study was guided by the principles of community-based participatory research . Hemoglobin A1c ( HbA1c ) level was the primary outcome measure . Using an empowerment-based approach , community health workers provided participants with diabetes self-management education and regular home visits , and accompanied them to a clinic visit during the 6-month intervention period . RESULTS Participants in the intervention group had a mean HbA1c value of 8.6 % at baseline , which improved to a value of 7.8 % at 6 months , for an adjusted change of -0.8 percentage points ( P < .01 ) . There was no change in mean HbA1c among the control group ( 8.5 % ) . Intervention participants also had significantly greater improvements in self-reported diabetes underst and ing compared with the control group . CONCLUSIONS This study contributes to the growing evidence for the effectiveness of community health workers and their role in multidisciplinary teams engaged in culturally appropriate health care delivery Significant racial disparities in cancer mortality are seen between Medicare beneficiaries . A r and omized controlled trial tested the use of lay navigators ( care managers ) to increase cancer screening of Asian and Pacific Isl and er Medicare beneficiaries . The study setting was Moloka'i General Hospital on the isl and of Moloka'i , Hawai'i , which was one of six sites participating in the Cancer Prevention and Treatment Demonstration sponsored by the Centers for Medicare and Medicaid Services . Between 2006 and 2009 , 488 Medicare beneficiaries ( 45 % Hawaiian , 35 % Filipino , 11 % Japanese , 8 % other ) were r and omized to have a navigator help them access cancer screening services ( experimental condition , n = 242 ) or cancer education ( control condition , n = 246 ) . Self-reported data on screening participation were collected at baseline and exit from the study , and differences were tested using chi-square . Groups were similar in demographic characteristics and baseline screening prevalence of breast , cervical , prostate , and colorectal cancers . At study exit , 57.0 % of women in the experimental arm and 36.4 % of controls had had a Papanicolaou test in the past 24 months ( P = .001 ) , 61.7 % of women in the experimental arm and 42.4 % of controls had had a mammogram in the past 12 months ( P = .003 ) , 54.4 % of men in the experimental arm and 36.0 % of controls had had a prostate-specific antigen test in the past 12 months ( P = .008 ) , and 43.0 % of both sexes in the experimental arm and 27.2 % of controls had had a flexible sigmoidoscopy or colonoscopy in the past 5 years ( P < .001 ) . Findings suggest that navigation services can increase cancer screening in Medicare beneficiaries in groups with significant disparities Objectives To describe ( 1 ) cardiac rehabilitation ( CR ) referral across cardiac units in a tertiary centre with eReferral ; ( 2 ) characteristics associated with CR referral and enrolment and ( 3 ) the effects of peer navigation ( PN ) on referral and enrolment . This pilot was a 2 parallel-arm , r and omised , single-blind trial with allocation concealment . Setting 3 cardiac units ( ie , interventional , general cardiology , and cardiac surgery ) in 1 of 2 hospitals of a tertiary centre . Participants CR-eligible adult cardiac in patients were r and omised to PN or usual care . 94 ( 54.7 % ) patients consented , of which 46 ( 48.9 % ) were r and omised to PN . Outcomes were ascertained in 76 ( 80.9 % ) participants . Intervention The PN ( 1 ) visited participant at the bedside , ( 2 ) mailed a card to participant 's home reminding about CR and ( 3 ) called participant 2 weeks postdischarge to discuss CR barriers . Outcome measures The primary outcome of enrolment was defined as participant attendance at a scheduled CR intake appointment ( yes/no ) . The secondary outcome was referral . Blinded outcome assessment was conducted 12 weeks postdischarge , via CR chart extraction . Results Those who received care on the cardiac surgery unit ( 77.9 % ) were more likely to be referred than those treated on the general cardiology ( 61.1 % ) or interventional unit ( 33.3 % ; p=0.04 ) . Patients who had cardiac surgery , hypertension and hyperlipidaemia were significantly more likely , and those with congenital heart disease , cancer and a previous cardiac diagnosis were less likely to be referred . Participants referred to a site closer to home ( 76.2 % of those referred ) were more likely to enrol than those not ( 23.7 % , p<0.05 ) . PN had no effect on referral ( 77.6 % , p=0.45 ) or enrolment ( 46.0 % , p=0.24 ) . Conclusions There is wide variability in CR referral , even within academic centres , and despite eReferral . Referral was quite high , and thus , PN did not improve CR utilisation . Results support triaging patients to the CR programme closest to their home . Trial registration number NCT02204449 ; Results Background : A fraction of HIV-diagnosed individuals promptly initiate antiretroviral therapy ( ART ) . We evaluated the efficacy of health system navigators for improving linkage to HIV and tuberculosis ( TB ) care among newly diagnosed HIV-infected out patients in Durban , South Africa . Methods : We conducted a r and omized controlled trial ( Sizanani Trial , NCT01188941 ) among adults ( ≥18 years ) at 4 sites . Participants underwent TB screening and r and omization into a health system navigator intervention or usual care . Intervention participants had an in-person interview at enrollment and received phone calls and text messages over 4 months . We assessed 9-month outcomes via medical records and the National Population Registry . Primary outcome was completion of at least 3 months of ART or 6 months of TB treatment for coinfected participants . Results : Four thous and nine hundred three participants were enrolled and r and omized ; 1899 ( 39 % ) were HIV-infected , with 1146 ( 60 % ) ART-eligible and 523 ( 28 % ) TB coinfected at baseline . In the intervention , 212 ( 39 % of outcome -eligible ) reached primary outcome compared to 197 ( 42 % ) in usual care ( RR 0.93 , 95 % CI : 0.80 to 1.08 ) . One hundred thirty-one ( 14 % ) HIV-infected intervention participants died compared to 119 ( 13 % ) in usual care ; death rates did not differ between arms ( RR 1.06 , 95 % CI : 0.84 to 1.34 ) . In the as-treated analysis , participants reached for ≥5 navigator calls were more likely to achieve study outcome . Conclusions : ∼40 % of ART-eligible participants in both study arms reached the primary outcome 9 months after HIV diagnosis . Low rates of engagement in care , high death rates , and lack of navigator efficacy highlight the urgency of identifying more effective strategies for improving HIV and TB care outcomes Background : This r and omized , controlled trial assessed the impact of a tailored navigation intervention versus a st and ard mailed intervention on colorectal cancer screening adherence and screening decision stage ( SDS ) . Methods : Primary care patients ( n = 945 ) were surveyed and r and omized to a Tailored Navigation Intervention ( TNI ) Group ( n = 312 ) , St and ard Intervention ( SI ) Group ( n = 316 ) , or usual care Control Group ( n = 317 ) . TNI Group participants were sent colonoscopy instructions and /or stool blood tests according to reported test preference , and received a navigation call . The SI Group was sent both colonoscopy instructions and stool blood tests . Multivariable analyses assessed intervention impact on adherence and change in SDS at 6 months . Results : The primary outcome , screening adherence ( TNI Group : 38 % , SI Group : 33 % , Control Group : 12 % ) , was higher for intervention recipients than controls ( P = 0.001 and P = 0.001 , respectively ) , but the two intervention groups did not differ significantly ( P = 0.201 ) . Positive SDS change ( TNI Group : + 45 % , SI Group : + 37 % , and Control Group : + 23 % ) was significantly greater among intervention recipients than controls ( P = 0.001 and P = 0.001 , respectively ) , and the intervention group difference approached significance ( P = 0.053 ) . Secondary analyses indicate that tailored navigation boosted preferred test use , and suggest that intervention impact on adherence and SDS was attenuated by limited access to screening options . Conclusions : Both interventions had significant , positive effects on outcomes compared with usual care . TNI versus SI impact had a modest positive impact on adherence and a pronounced effect on SDS . Impact : Mailed screening tests can boost adherence . Research is needed to determine how preference , access , and navigation affect screening outcomes . Cancer Epidemiol Biomarkers Prev ; 22(1 ) ; 109–17 . © 2012 AACR INTRODUCTION Mammography is underused by certain groups of women , in particular poor and minority women . We developed a lay health advisor ( LHA ) intervention based on behavioral theories and tested whether it improved mammography attendance in Robeson County , NC , a rural , low-income , triracial ( white , Native American , African American ) population . METHODS A total of 851 women who had not had a mammogram within the past year were r and omly assigned to the LHA intervention ( n = 433 ) or to a comparison arm ( n = 418 ) during 1998 - 2002 . Rates of mammography use after 12 - 14 months ( as verified by medical record review ) were compared using a chi-square test . Baseline and follow-up ( at 12 - 14 months ) surveys were used to obtain information on demographics , risk factors , and barriers , beliefs , and knowledge about mammography . Linear regression , Mantel-Haenszel statistics , and logistic regression were used to compare barriers , beliefs , and knowledge from baseline to follow-up and to identify baseline factors associated with mammography . RESULTS At follow-up , 42.5 % of the women in the LHA group and 27.3 % of those in the comparison group had had a mammogram in the previous 12 months ( relative risk = 1.56 , 95 % confidence interval [ CI ] = 1.29 to 1.87 ) . Compared with those in the comparison group , women in the LHA group displayed statistically significantly better belief scores ( difference = 0.46 points on a 0 - 10 scale , 95 % CI = 0.15 to 0.77 ) and reduced barriers at follow-up ( difference = -0.77 points , 95 % CI = -1.02 to -0.53 ) , after adjusting for baseline scores . CONCLUSIONS LHA interventions can improve mammography utilization . Future studies are needed to assess strategies to disseminate effective LHA interventions to underserved population BACKGROUND North American Chinese women have lower levels of Papanicolaou ( Pap ) testing than other population subgroups . We conducted a r and omized controlled trial to evaluate the effectiveness of two alternative cervical cancer screening interventions for Chinese women living in North America . METHODS Four hundred and eighty-two Pap testing underutilizers were identified from community-based surveys of Chinese women conducted in Seattle , Washington , and Vancouver , British Columbia . These women were r and omly assigned to one of two experimental arms or control status . Several Chinese- language material s were used in both experimental arms : an education-entertainment video , a motivational pamphlet , an educational brochure , and a fact sheet . Women in the first experimental group ( outreach worker intervention ) received the material s , as well as tailored counseling and logistic assistance , during home visits by trilingual , bicultural outreach workers . Those in the second experimental group ( direct mail intervention ) received the material s by mail . The control group received usual care . Follow-up surveys were completed 6 months after r and omization to ascertain participants ' Pap testing behavior . All statistical tests were two-sided . RESULTS A total of 402 women responded to the follow-up survey ( 83 % response rate ) . Of these women , 50 ( 39 % ) of the 129 women in the outreach group , 35 ( 25 % ) of the 139 women in the direct mail group , and 20 ( 15 % ) of the 134 women in the control group reported Pap testing in the interval between r and omization and follow-up data collection ( P<.001 for outreach worker versus control , P = .03 for direct mail versus control , and P = .02 for outreach worker versus direct mail ) . Intervention effects were greater in Vancouver than in Seattle . CONCLUSION Culturally and linguistically appropriate interventions may improve Pap testing levels among Chinese women in North America Objectives . Although people with HIV experience significant oral health problems , many consistently identify oral health as an unmet health care need . We conducted a r and omized controlled trial to evaluate the impact of a dental case management intervention on dental care use . Methods . We evaluated the intervention according to self-reported dental care use at 6- , 12- , and 18-month follow-ups . Multivariable logistic models with generalized estimating equations were used to assess the effects of the intervention over time . Results . The odds of having a dental care visit were about twice as high in the intervention group as in the st and ard care group at 6 months ( adjusted odds ratio [ OR ] = 2.52 ; 95 % confidence interval [ CI ] = 1.58 , 4.08 ) and 12 months ( adjusted OR = 1.98 ; 95 % CI = 1.17 , 3.35 ) , but the odds were comparable in the 2 groups by 18 months ( adjusted OR = 1.07 ; 95 % CI = 0.62 , 1.86 ) . Factors significantly associated with having a dental care visit included frequent physician visits and dental care referrals . Conclusions . We demonstrated that a dental case management intervention targeting people with HIV was efficacious but not sustainable over time . Barriers not addressed in the intervention must be considered to sustain its use over time BACKGROUND AND OBJECTIVES Many patients with ESRD , particularly minorities and women , face barriers in completing the steps required to obtain a transplant . These eight sequential steps are as follows : medical suitability , interest in transplant , referral to a transplant center , first visit to center , transplant workup , successful c and i date , waiting list or identify living donor , and receive transplant . This study sought to determine the effect of navigators on completion of steps . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Cluster r and omized , controlled trial at 23 Ohio hemodialysis facilities . One hundred sixty-seven patients were recruited between January 2009 and August 2009 and were followed for up to 24 months or until study end in February 2011 . Trained kidney transplant recipients met monthly with intervention participants ( n=92 ) , determined their step in the transplant process , and provided tailored information and assistance in completing the step . Control participants ( n=75 ) continued to receive usual care . The primary outcome was the number of transplant process steps completed . RESULTS Starting step did not significantly differ between the two groups . By the end of the trial , intervention participants completed more than twice as many steps as control participants ( 3.5 versus 1.6 steps ; difference , 1.9 steps ; 95 % confidence interval , 1.3 - 2.5 steps ) . The effect of the intervention on step completion was similar across race and sex subgroups . CONCLUSIONS Use of trained transplant recipients as navigators result ed in increased completion of transplant process steps PURPOSE Peer health coaches offer a potential model for extending the capacity of primary care practice s to provide self-management support for patients with diabetes . We conducted a r and omized controlled trial to test whether clinic-based peer health coaching , compared with usual care , improves glycemic control for low-income patients who have poorly controlled diabetes . METHOD We undertook a r and omized controlled trial enrolling patients from 6 public health clinics in San Francisco . Twenty-three patients with a glycated hemoglobin ( HbA1C ) level of less than 8.5 % , who completed a 36-hour health coach training class , acted as peer coaches . Patients from the same clinics with HbA1C levels of 8.0 % or more were recruited and r and omized to receive health coaching ( n = 148 ) or usual care ( n = 151 ) . The primary outcome was the difference in change in HbA1C levels at 6 months . Secondary outcomes were proportion of patients with a decrease in HbA1C level of 1.0 % or more and proportion of patients with an HbA1C level of less than 7.5 % at 6 months . Data were analyzed using a linear mixed model with and without adjustment for differences in baseline variables . RESULTS At 6 months , HbA1C levels had decreased by 1.07 % in the coached group and 0.3 % in the usual care group , a difference of 0.77 % in favor of coaching ( P = .01 , adjusted ) . HbA1C levels decreased 1.0 % or more in 49.6 % of coached patients vs 31.5 % of usual care patients ( P = .001 , adjusted ) , and levels at 6 months were less than 7.5 % for 22.0 % of coached vs 14.9 % of usual care patients ( P = .04 , adjusted ) . CONCLUSIONS Peer health coaching significantly improved diabetes control in this group of low-income primary care patients Background Lower mammography screening rates among minority and low income women contribute to increased morbidity and mortality from breast cancer . Objective To evaluate the effect of a patient navigation intervention on adherence rates to biennial screening mammography among women engaged in primary care at an inner-city academic medical center . Design Quality improvement intervention with a concurrent control group , conducted from February to November of 2008 . Study SubjectsAll women in a hospital-based primary care practice aged 51–70 years . Subjects were r and omized at the level of their primary care provider , such that half of the patients in the practice received the intervention , while the other half received usual care . Interventions Intervention subjects whose last mammogram was > 18 months prior received a combination of telephone calls and reminder letters from patient navigators trained to identify barriers to care . Navigators were integrated into primary care teams and interacted directly with patients , providers , and radiology to coordinate care . Navigators utilized an electronic report to track subjects . Adherence rates to biennial mammography were assessed in intervention and control groups at baseline and post-intervention . Key Results A total of 3,895 women were r and omized to intervention ( n = 1,817 ) and control ( n = 2,078 ) groups . Mean age was 60 , 71 % were racial/ethnic minorities , 23 % were non-English speaking , and 63 % had public or no health insurance . At baseline , there was no difference in mammography adherence between the control and intervention groups ( 78 % , respectively , p = 0.55 ) . After the 9-month intervention , mammogram adherence was higher in the intervention group compared with the control group ( 87 % vs. 76 % , respectively , p < 0.001 ) . Except among Hispanic women who demonstrated high rates in both the intervention and control groups ( 85 % and 83 % , respectively ) , all racial/ethnic and insurance groups demonstrated higher adherence in the intervention group . Conclusions Patient navigation improves biennial mammography rates for inner city , low income , minority population Background : Patient navigation ( PN ) has been suggested as a way to reduce cancer health disparities ; however , many models of PN exist and most have not been carefully evaluated . The goal of this study was to test the Ohio American Cancer Society model of PN as it relates to reducing time to diagnostic resolution among persons with abnormal breast , cervical , or colorectal cancer screening tests or symptoms . Methods : A total of 862 patients from 18 clinics participated in this group-r and omized trial . Chart review documented the date of the abnormality and the date of resolution . The primary analysis used shared frailty models to test for the effect of PN on time to resolution . Crude HR were reported as there was no evidence of confounding . Results : HRs became significant at 6 months ; conditional on the r and om clinic effect , the resolution rate at 15 months was 65 % higher in the PN arm ( P = 0.012 for difference in resolution rate across arms ; P = 0.009 for an increase in the HR over time ) . Conclusions : Participants with abnormal cancer screening tests or symptoms resolved faster if assigned to PN compared with those not assigned to PN . The effect of PN became apparent beginning six months after detection of the abnormality . Impact : PN may help address health disparities by reducing time to resolution after an abnormal cancer screening test . Cancer Epidemiol Biomarkers Prev ; 21(10 ) ; 1620–8 . © 2012 AACR BACKGROUND A r and omized , controlled trial was conducted to evaluate the impact of a directly administered antiretroviral therapy program ( DAART ) and intensive adherence case management ( IACM ) intervention on virologic and immunologic response to highly active antiretroviral therapy ( HAART ) among patients at 3 public human immunodeficiency virus clinics in Los Angeles County , California . METHODS Participants included 250 treatment-naive and treatment-experienced persons for whom no more than 1 prior HAART regimen had failed . Five days per week for 6 months , a community worker delivered 1 HAART dose to DAART participants and observed the participant take it . IACM participants met weekly with a case manager to overcome barriers to HAART adherence . A control group ( the st and ard of care [ SOC ] group ) received the usual care . RESULTS The majority of patients were Latino ( 64 % ) or African American ( 24 % ) ; 57 % were monolingual Spanish speakers . Seventy-five percent of the patients were male , and 64 % reported an annual income of < 10,000 dollars . In an intent-to-treat analysis , no statistical differences were observed in the percentage of patients with an undetectable viral load ( i.e. , < 400 copies/mL ) at 6 months between the DAART group ( 54 % ) , IACM group ( 60 % ) , and SOC group ( 54 % ; P>.05 ) . An on-treatment analysis determined that there were no statistical differences in the percentage of patients with an undetectable viral load at 6 months between the DAART group ( 71 % ) , IACM group ( 80 % ) , and SOC group ( 74 % ; P>.05 ) . Additionally , there were no statistical differences in 6-month changes in the CD4 + cell count or in self-reported adherence to therapy . CONCLUSIONS Among patients with limited prior HAART experience and adherence barriers that had not been assessed before r and omization , no differences were found in virologic or immunologic response for DAART or IACM , compared with SOC , at 6 months . DAART and IACM did not improve short-term outcomes when SOC included other means of adherence support that were not controlled for by the study design INTRODUCTION Colorectal cancer is a leading cause of cancer-related death in the U.S. Although screening reduces colorectal cancer incidence and mortality , screening rates among U.S. adults remain less than optimal , especially among disadvantaged population s. This study examined the efficacy of patient navigation to increase colonoscopy screening . STUDY DESIGN RCT . SETTING / PARTICIPANTS A total of 843 low-income adults , primarily Hispanic and non-Hispanic blacks , aged 50 - 75 years referred for colonoscopy at Boston Medical Center were r and omized into the intervention ( n=429 ) or control ( n=427 ) groups . Participants were enrolled between September 2012 and December 2014 , with analysis following through 2015 . INTERVENTION Two bilingual lay navigators provided individualized education and support to reduce patient barriers and facilitate colonoscopy completion . The intervention was delivered largely by telephone . MAIN OUTCOME MEASURE Colonoscopy completion within 6 months of study enrollment . RESULTS Colonoscopy completion was significantly higher for navigated patients ( 61.1 % ) than control group patients receiving usual care ( 53.2 % , p=0.021 ) . Based on regression analysis , the odds of completing a colonoscopy for navigated patients was one and a half times greater than for controls ( 95 % CI=1.12 , 2.03 , p=0.007 ) . There were no differences between navigated and control groups in regard to adequacy of bowel preparation ( 95.3 % vs 97.3 % , respectively ) . CONCLUSIONS Navigation significantly improved colonoscopy screening completion among a racially diverse , low-income population . Results contribute to mounting evidence demonstrating the efficacy of patient navigation in increasing colorectal cancer screening . Screening can be further enhanced when navigation is combined with other evidence -based practice s implemented in healthcare systems and the community BACKGROUND Few interventions have been shown to improve retention in human immunodeficiency virus ( HIV ) care , and none have targeted the hospitalized patient . Peer mentoring has not been rigorously tested . METHODS We conducted a r and omized , controlled clinical trial of a peer mentoring intervention . Eligible adults were hospitalized and were either newly diagnosed with HIV infection or out of care . The intervention included 2 in-person sessions with a volunteer peer mentor while hospitalized , followed by 5 phone calls in the 10 weeks after discharge . The control intervention provided didactic sessions on avoiding HIV transmission on the same schedule . The primary outcome was a composite of retention in care ( completed HIV primary care visits within 30 days and between 31 and 180 days after discharge ) and viral load ( VL ) improvement ( ≥1 log10 decline ) 6 months after discharge . RESULTS We enrolled 460 participants in 3 years ; 417 were in the modified intent-to-treat analysis . The median age was 42 years ; 74 % were male ; and 67 % were non-Hispanic black . Baseline characteristics did not differ between the r and omized groups . Twenty-eight percent of the participants in both arms met the primary outcome ( P = .94 ) . There were no differences in prespecified secondary outcomes , including retention in care and VL change . Post hoc analyses indicated interactions between the intervention and length of hospitalization and between the intervention and receipt of linkage services before discharge . CONCLUSIONS Peer mentoring did not increase reengagement in outpatient HIV care among hospitalized , out-of-care persons . More intense and system-focused interventions warrant further study . CLINICAL TRIALS REGISTRATION NCT01103856 Background Minority racial/ethnic groups have low colorectal cancer ( CRC ) screening rates . Objective To evaluate a culturally tailored intervention to increase CRC screening , primarily using colonoscopy , among low income and non-English speaking patients . Design R and omized controlled trial conducted from January to October of 2007 . Setting Single , urban community health center serving a low-income , ethnically diverse population . Patients A total of 1,223 patients 52 - 79 years of age overdue for CRC screening , r and omized to intervention ( n = 409 ) vs. usual care control ( n = 814 ) groups . InterventionIntervention patients received an introductory letter with educational material followed by phone or in-person contact by a language -concordant “ navigator . ” Navigators ( n = 5 ) were community health workers trained to identify and address patient-reported barriers to CRC screening . Individually tailored interventions included patient education , procedure scheduling , translation and explanation of bowel preparation , and help with transportation and insurance coverage . Rates of colorectal cancer screening were assessed for intervention and usual care control patients . Results Over a 9-month period , intervention patients were more likely to undergo CRC screening than control patients ( 27 % vs. 12 % for any CRC screening , p < 0.001 ; 21 % vs. 10 % for colonoscopy completion , p < 0.001 ) . The higher screening rate result ed in the identification of 10.5 polyps per 100 patients in the intervention group vs. 6.8 in the control group ( p = 0.04 ) . Limitations Patients were from one health center . Some patients may have obtained CRC screening outside our system . Conclusions A culturally tailored , language -concordant navigator program design ed to identify and overcome barriers to colorectal cancer screening can significantly improve colonoscopy rates for low income , ethnically and linguistically diverse patients . Clinical Trials.gov registration number : Purpose This study investigated the effectiveness of a structured telephone intervention for caregivers of people diagnosed with poor prognosis gastrointestinal cancer to improve psychosocial outcomes for both caregivers and patients . Methods Caregivers of patients starting treatment for upper gastrointestinal or Dukes D colorectal cancer were r and omly assigned ( 1:1 ) to the Family Connect telephone intervention or usual care . Caregivers in the intervention group received four st and ardized telephone calls in the 10 weeks following patient hospital discharge . Caregivers ’ quality of life ( QOL ) , caregiver burden , unmet supportive care needs and distress were assessed at 3 and 6 months . Patients ’ QOL , unmet supportive care needs , distress and health service utilization were also assessed at these time points . Results Caregivers ( 128 ) were r and omized to intervention or usual care groups . At 3 months , caregiver QOL scores and other caregiver-reported outcomes were similar in both groups . Intervention group participants experienced a greater sense of social support ( p = .049 ) and reduced worry about finances ( p = .014 ) . Patients whose caregiver was r and omized to the intervention also had fewer emergency department presentations and unplanned hospital readmissions at 3 months post-discharge ( total 17 vs. 5 , p = .01 ) . Conclusions This st and ardized intervention did not demonstrate any significant improvements in caregiver well-being but did result in a decrease in patient emergency department presentations and unplanned hospital readmissions in the immediate post-discharge period . The trend towards improvements in a number of caregiver outcomes and the improvement in health service utilization support further development of telephone-based caregiver-focused supportive care interventions OBJECTIVE Both acute and chronic complications of diabetes account for a disproportionate percentage of US health care expenditures . Despite improvements in diabetes care , the incidence of adverse events in children with type 1 diabetes remains high , particularly for youths with poor glycemic control . Cost-effective intervention programs design ed to reduce complications are needed . This study evaluated a low-intensity , nonmedical intervention using a case manager ( called a " Care Ambassador " ) , with and without the supplementation of psychoeducational modules , design ed to monitor and encourage routine diabetes care visits to reduce short-term adverse outcomes and improve glycemic control in youths with type 1 diabetes . METHODS We performed a 2-year prospect i ve , r and omized clinical trial in 299 youths with type 1 diabetes , aged 7 to 16 years , comparing 3 treatment programs ( Care Ambassador [ CA ] , Care Ambassador plus psychoeducational modules [ CA+ ] , and st and ard multidisciplinary diabetes care [ SC ] ) . The study was conducted in a large metropolitan US city from April 1997 through April 2000 . Number of medical visits , frequency of hypoglycemic events , hospital/emergency department ( ED ) utilization , and glycosylated hemoglobin A1c were assessed during follow-up . RESULTS During the 2-year study period , both the CA and CA+ groups had significantly more routine visits ( mean [ st and ard deviation ] : 7.3 [ 2.06 ] and 7.5 [ 2.02 ] , respectively ) compared with the SC group ( 5.4 [ 2.62 ] ) . The CA+ intervention group had significantly reduced rates of short-term adverse outcomes compared with the other 2 groups ; 25 % fewer total hypoglycemic events , 60 % fewer severe hypoglycemic events , and 40 % fewer hospitalizations and ED visits . " High-risk " youths in the CA+ group ( baseline glycosylated hemoglobin A1c > or = 8.7 % ) were 3.4-fold ( 1.57 - 7.41 ) more likely to improve their glycemic control compared with those at high risk in the other 2 groups . CONCLUSIONS For youths with type 1 diabetes , the CA and CA+ interventions increased visit frequency . Youths in the CA+ intervention had reduced rates of hypoglycemia and hospital/ED utilization with estimated annual cost savings of 80 000 dollars to 90 000 dollars . The CA+ intervention compared with the other 2 groups improved glycemic control in " high-risk " youths . Nonmedical case management incorporating psychoeducational modules seems to be a cost-effective approach to improving outcomes in youths with diabetes Few studies have investigated community clinic-based interventions to promote mammography screening among rural African American women . This study r and omized older low-income rural African American women who had not participated in screening in the previous 2 years to a theory-based , personalized letter or usual care ; no group differences in mammography rate were evident at 6-month follow-up . Women who had not obtained a mammogram were then r and omized to a tailored call delivered by community health care workers or a tailored letter . There were no group differences in mammography rates after the second 6-month follow-up . However , among women who had never had a mammogram , the tailored call was more effective in promoting mammography use . Tailored counseling may be an effective screening promotion strategy for hard-to-reach rural African American women with no history of screening . Further research into this strategy may facilitate efforts to reduce health disparities in underserved low-income rural African American population The objective of the study was to determine the effectiveness and cost-effectiveness of primary care and community-oriented interventions in managing HbA1c , blood pressure , and lipids , and reducing hospitalizations and emergency room visits over 2 years . We describe an ongoing , r and omized controlled trial of 542 urban African-Americans with type 2 diabetes ages 25 years and older who are members of a university-affiliated managed-care organization in Baltimore , MD . The participants are 74 % female , have a mean age of 58 years , and 35 % have yearly incomes greater than 7500 US dollars . Participants were r and omized to one of two intervention groups for a period of 2 years : ( 1 ) usual medical care plus minimal telephone intervention implemented by a trained lay health educator ( control group ) or ( 2 ) usual medical care plus intensive intervention implemented by a nurse case manager (NCM)/community health worker ( CHW ) team . The intensive NCM/CHW team executes individual plans of care using evidence -based algorithms that focus on traditional diabetes self-management , screening and management of diabetes-related complications , and social issues surrounding diabetes care . Face-to-face NCM visits are conducted in the clinic once per year and CHW visits are conducted in the participant 's home one to three times per year , both with additional follow-up contacts as needed . Written and verbal feedback ( when necessary ) is provided to the participant 's primary care physician . All participants are expected to attend a 24-month follow-up visit where data are collected by interviewers blinded to intervention assignment . As of May 1 , 2003 , recruitment is complete , interventions are being fully implemented , and 24-month follow-up visits are beginning . Baseline sociodemographic characteristics , health-care utilization , health behaviors , and clinical characteristics of the study population are reported . This study is design ed to test the hypothesis that a primary -care-based NCM plus CHW team approach is an effective , practical , and economically feasible strategy for translating current knowledge about type 2 diabetes into high- quality health care for urban African-Americans OBJECTIVES We evaluated the effectiveness of a community-based participatory research -grounded intervention among women receiving Temporary Assistance for Needy Families ( TANF ) with chronic health conditions in increasing ( 1 ) health care visits , ( 2 ) Medicaid knowledge and skills , and ( 3 ) health and functional status . METHODS We used a r and omized controlled trial design to assign 432 women to a public health nurse case management plus Medicaid intervention or a wait-control group . We assessed Medicaid outcomes pre- and posttraining ; other outcomes were assessed at 3 , 6 , and 9 months . RESULTS Medicaid knowledge and skills improved ( P < .001 for both ) . Intervention group participants were more likely to have a new mental health visit ( odds ratio [ OR ] = 1.92 ; P = .007 ) , and this likelihood increased in higher-risk subgroups ( OR = 2.03 and 2.83 ; P = .04 and .006 , respectively ) . Depression and functional status improved in the intervention group over time ( P = .016 for both ) . No differences were found in routine or preventive care , or general health . CONCLUSIONS Health outcomes among women receiving TANF can be improved with public health interventions . Additional strategies are needed to further reduce health disparities in this population BACKGROUND AND OBJECTIVES Patient navigators and enhanced personal health records improve the quality of health care delivered in other disease states . We aim ed to develop a navigator program for patients with CKD and an electronic health record-based enhanced personal health record to disseminate CKD stage-specific goals of care and education . We also conducted a pragmatic r and omized clinical trial to compare the effect of a navigator program for patients with CKD with enhanced personal health record and compare their combination compared with usual care among patients with CKD stage 3b/4 . DESIGN , SETTING , PARTICIPANTS , & MEASUREMENTS Two hundred and nine patients from six outpatient clinics ( in both primary care and nephrology setting s ) were r and omized in a 2 × 2 factorial design into four- study groups : ( 1 ) enhanced personal health record only , ( 2 ) patient navigator only , ( 3 ) both , and ( 4 ) usual care ( control ) group . Primary outcome measure was the change in eGFR over a 2-year follow-up period . Secondary outcome measures included acquisition of appropriate CKD-related laboratory measures , specialty referrals , and hospitalization rates . RESULTS Median age of the study population was 68 years old , and 75 % were white . At study entry , 54 % of patients were followed by nephrologists , and 88 % were on renin-angiotensin system blockers . After a 2-year follow-up , rate of decline in eGFR was similar across the four groups ( P=0.19 ) . Measurements of CKD-related laboratory parameters were not significantly different among the groups . Furthermore , referral for dialysis education and vascular access placement , emergency room visits , and hospitalization rates were not statistically significant different between the groups . CONCLUSIONS We successfully developed a patient navigator program and an enhanced personal health record for the CKD population . However , there were no differences in eGFR decline and other outcomes among the study groups . Larger and long-term studies along with cost-effectiveness analyses are needed to evaluate the role of patient navigators and patient education through an enhanced personal health record in those with CKD Organizational barriers play a key role in colorectal cancer ( CRC ) screening disparities in low-income minorities . This is a prospect i ve , r and omized trial to determine whether a patient navigator ( PN ) can help overcome the organizational barriers low-income minorities face in trying to obtain screening colonoscopy . Patients of average risk for CRC were referred by their primary care physician for screening colonoscopy . After the PN received the referral , patients were r and omly assigned to either receive navigation ( PN+ ) to screening colonoscopy or not receive navigation ( PN- ) . We hypothesized that a PN would increase patient compliance with screening colonoscopy . A total of 21 patients were enrolled in the pilot study ( PN+ = 13 , PN- = 8) ; 54 % of navigated patients completed screening colonoscopy versus 13 % of nonnavigated patients ( p = 0.058 ) . Eighty-six percent of navigated patients had an excellent or very good colon prep ; however , there was no difference in prep quality between groups ( p = 0.10 ) . One-hundred percent of navigated patients were very satisfied with navigation services . A PN improves compliance with screening colonoscopy in low-income minorities . Larger studies are needed to evaluate what features of navigation are most effective in facilitating completion of screening colonoscopy OBJECTIVE The objective was to assess the effectiveness of a volunteer-delivered tailored telephone-based intervention in reducing prevalence of unmet supportive care needs , elevated levels of anxiety and depression among people with colorectal cancer over a 9-month period . METHODS There were 653 participants who completed the baseline question naire and were r and omised to usual care ( n = 341 ) or intervention ( n = 306 ) . Three follow-up question naires were completed at 3-monthly intervals ( response rates : 93 % , 87 % , 82 % , respectively ) . All four question naires contained the Supportive Care Needs Survey ( SCNS ) , Hospital Anxiety and Depression Scale ( HADS ) and checklists for colorectal cancer symptoms and use of support services . The intervention consisted of trained volunteers providing emotional support , service referral and information and was delivered after completion of each of the first three question naires . Primary outcomes were prevalence of moderate to high SCNS needs and elevated levels ( scores of 8 + ) of HADS anxiety and depression . RESULTS Over the study period , SCNS needs decreased similarly for both groups , and prevalence of elevated depression did not change for either group . There was a greater reduction in the prevalence of elevated anxiety in the intervention than usual care group ( p < 0.01 ) , with the intervention group decrease mainly occurring between baseline and the first follow-up survey ( p < 0.01 ) . However , the prevalence of elevated anxiety was similar between the two groups at each follow-up point . CONCLUSIONS The intervention had no effect on supportive care needs or depression , although it may be associated with a greater reduction in anxiety . Future research should test the intervention with patients closer to diagnosis OBJECTIVES We sought to test the hypothesis that training medical assistants to provide health coaching would improve patients ' experience of care received and overall satisfaction with their clinic . STUDY DESIGN R and omized controlled trial . METHODS Low-income English- or Spanish-speaking patients aged 18 to 75 years with poorly controlled type 2 diabetes , hypertension , and /or hyperlipidemia were r and omized to receive either a health coach or usual care for 12 months . Patient care experience was measured using the Patient Assessment of Chronic Illness Care ( PACIC ) scale at baseline and at 12 months . Patient overall satisfaction with the clinic was assessed with a single item asking if they would recommend the clinic to a friend or family member . PACIC and satisfaction scores were compared between study arms using generalized estimating equations to account for clustering at the clinician level . RESULTS PACIC scores were available from baseline and at 12 months on 366 ( 76 % ) of the 441 patients r and omized . At baseline , patients receiving health coaching were similar to those in the usual care group with respect to demographic and other characteristics , including mean PACIC scores ( 3.00 vs 3.06 ) and the percent who would " definitely recommend " their clinic ( 73 % and 73 % , respectively ) . At 12 months , coached patients had a significantly higher mean PACIC score ( 3.82 vs 3.13 ; P < .001 ) and were more likely to report they would definitely recommend their clinic ( 85 % vs 73 % ; P = .002 ) . CONCLUSIONS Using medical assistants trained in health coaching significantly improved the quality of care that low-income patients with poorly controlled chronic disease reported receiving from their healthcare team ABSTRACT BACKGROUND There is growing evidence that patient navigation improves breast cancer screening rates ; however , there are limited efficacy studies of its effect among African American older adult women . OBJECTIVE To evaluate the effect of patient navigation on screening mammography among African American female Medicare beneficiaries in Baltimore , MD . DESIGN The Cancer Prevention and Treatment Demonstration ( CPTD ) , a multi-site study , was a r and omized controlled trial conducted from April 2006 through December 2010 . SETTING Community-based and clinical setting . PARTICIPANTS The CPTD Screening Trial enrolled 1905 community-dwelling African American female Medicare beneficiaries who were ≥65 years of age and resided in Baltimore , MD . Participants were recruited from health clinics , community centers , health fairs , mailings using Medicare rosters , and phone calls . INTERVENTIONS Participants were r and omized to either : printed educational material s on cancer screening ( control group ) or printed educational material s + patient navigation services design ed to help participants overcome barriers to cancer screening ( intervention group).MAIN MEASURES elf-reported receipt of mammography screening within 2 years of the end of the study .KEY RESULTS The median follow-up period for participants in this analysis was 17.8 months . In weighted multivariable logistic regression analyses , women in the intervention group had significantly higher odds of being up to date on mammography screening at the end of the follow-up period compared to women in the control group ( odds ratio [ OR ] 2.26 , 95 % confidence interval [CI]1.59–3.22 ) . The effect of the intervention was stronger among women who were not up to date with mammography screening at enrollment ( OR 3.63 , 95 % CI 2.09–6.38 ) . CONCLUSION Patient navigation among urban African American Medicare beneficiaries increased self-reported mammography utilization . The results suggest that patient navigation for mammography screening should focus on women who are not up to date on their screening Background : The expectation that insurance coverage mitigates health disparities and equalizes use of healthcare assumes that services are equally accessed ; however , the insured low-income target population in this research had a mammography rate of 23.4 % , well below the general population . Our objective was to determine the most effective intervention to improve mammography use in low-income women insured by a managed care organization ( MCO ) . Methods : The study was a r and omized controlled trial . Participants were 2,357 women noncompliant with screening mammography r and omly assigned to one of three groups : control ( n = 786 ) received usual care ; simple intervention ( n = 785 ) received prompt letter from the MCO medical director ; and stepwise intervention ( n = 786 ) received the same prompt letter from the MCO ; if noncompliant , a second prompt letter from their primary care physician and , if still noncompliant , counseling from lay health workers . Outcome was completion of screening mammography extracted from medical records . Results : Screening rates were 13.4 % for the control , 16.1 % for the simple intervention , and 27.1 % for the stepwise intervention . Compared with the control , the primary care physician letter in the stepwise intervention increased the likelihood of screening by 80 % [ Relative Risk ( RR ) = 1.80 ; P < 0.001 ] , and counseling tripled the likelihood of screening ( RR = 3.11 ; P < 0.001 ) . Conclusions : Compared with the control and simple intervention , a stepwise intervention to increase mammography is effective in a target population of hard-to-reach , low-income , insured women . Impact : The research provides evidence for the impact of stepwise interventions to improve cancer screening in low-income insured population s , although the screening rates remain well below those of the general population . Cancer Epidemiol Biomarkers Prev ; 19(7 ) ; 1790–8 . © 2010 AACR Colorectal cancer ( CRC ) is the second leading cause of cancer-related deaths in the United States . Racial disparities in CRC incidence and mortality have been well documented . In addition , lower rates of CRC screening among ethnic minorities have been reported . Therefore , we tested the effectiveness of a patient navigator ( PN ) in increasing compliance with CRC screening in a minority community health setting . Men and women aged 50 or older attending a primary care practice were enrolled if they had not had a fecal occult blood test within the past year , a sigmoidoscopy or barium enema within the past 3–5 years , or a colonoscopy within the past 10 years . Participants were r and omly assigned either to receive navigator services ( PN+ ) or not to receive navigator services ( PN− ) . There were no demographic differences between the two groups . Within 6 months of physician recommendation , 15.8 % in the PN+ group had complied with an endoscopic examination , compared with only 5 % in the PN− group ( P=.019 ) . The PN+ groups also demonstrated higher rates of fecal occult blood test completion ( 42.1 % vs. 25 % , P=.086 ) . Thus , a PN system successfully increases CRC screening rates among a predominantly minority population of low socioeconomic status Objective : The Antiretroviral Treatment Access Study ( ARTAS ) assessed a case management intervention to improve linkage to care for persons recently receiving an HIV diagnosis . Methods : Participants were recently diagnosed HIV-infected persons in Atlanta , Baltimore , Los Angeles and Miami . They were r and omized to either st and ard of care ( SOC ) passive referral or case management ( CM ) for linkage to nearby HIV clinics . The SOC arm received information about HIV and local care re sources ; the CM intervention arm included up to five contacts with a case manager over a 90-day period . The outcome measure was self-reported attendance at an HIV care clinic at least twice over a 12-month period . Results : A higher proportion of the 136 case-managed participants than the 137 SOC participants visited an HIV clinician at least once within 6 months [ 78 versus 60 % ; adjusted relative risk ( RRadj ) , 1.36 ; P = 0.0005 ) and at least twice within 12 months ( 64 versus 49 % ; RRadj , 1.41 ; P = 0.006 ) . Individuals older than 40 years , Hispanic participants , individuals enrolled within 6 months of an HIV-seropositive test result and participants without recent crack cocaine use were all significantly more likely to have made two visits to an HIV care provider . We estimate the cost of such case management to be US$ 600–1200 per client . Conclusion : A brief intervention by a case manager was associated with a significantly higher rate of successful linkage to HIV care . Brief case management is an affordable and effective re source that can be offered to HIV-infected clients soon after their HIV diagnosis Background : Barriers to timely resolution of abnormal cancer screening tests add to cancer health disparities among low-income , uninsured , and minority population s. We conducted a r and omized trial to evaluate the impact of lay patient navigators on time to resolution and completion of follow-up testing among patients with abnormal screening tests in a medically underserved patient population . Methods : Denver Health , the safety-net health care system serving Denver , is one of 10 performance sites participating in the Patient Navigation Research Program . Of 993 eligible subjects with abnormal screening tests r and omized to navigation and no-navigation ( control ) arms and analyzed , 628 had abnormal breast screens ( 66 abnormal clinical breast examinations , 304 BIRADS 0 , 200 BIRADS 3 , 58 BIRADS 4 or 5 ) whereas 235 had abnormal colorectal and 130 had abnormal prostate screens . Results : Time to resolution was significantly shorter in the navigated group ( stratified log rank test , P < 0.001 ) . Patient navigation improved diagnostic resolution for patients presenting with mammographic BIRADS 3 ( P = 0.0003 ) and BIRADS 0 ( P = 0.09 ) , but not BIRADS 4/5 or abnormal breast examinations . Navigation shortened the time for both colorectal ( P = 0.0017 ) and prostate screening resolution ( P = 0.06 ) . Participant demographics included 72 % minority , 49 % with annual household income less than $ 10,000 , and 36 % uninsured . Conclusions : Patient navigation positively impacts time to resolution of abnormal screening tests for breast , colorectal , and prostate cancers in a medically underserved population . Impact : By shortening the time to and increasing the proportion of patients with diagnostic resolution patient navigation could reduce disparities in stage at diagnosis and improve cancer outcomes . Cancer Epidemiol Biomarkers Prev ; 21(10 ) ; 1629–38 . © 2012 AACR Rarely has utilization of genetic counseling for Hereditary Breast and Ovarian Cancer ( HBOC ) been studied separately from utilization of testing . At Kaiser Permanente Colorado , consistently only 30 % of all members referred for HBOC attend genetic counseling . To increase the volume of genetic counseling appointments , a patient navigator approach was pilot tested in a r and omized-controlled trial over 3 months . A total of 125 members were referred for HBOC genetic counseling ( 55 r and omized to PN , 70 r and omized to usual care ) . Utilization of referrals for Navigator-assisted members was 44 % , compared to 31 % in the usual care arm ( p=0.16 ) . The patient navigator significantly decreased time to appointment , with over 80 % of Navigator-assisted members seen for genetic counseling less than three months from referral date , compared to 32 % in usual care ( p=0.002 ) . patient navigator assistance shortens time from referral to appointment for HBOC genetic counseling , and may increase utilization of such services Abstract Objective : To examine the effect of contact with a stroke family care worker on the physical , social , and psychological status of stroke patients and their carers . Design : R and omised controlled trial with broad entry criteria and blinded outcome assessment six months after r and omisation . Setting : A well organised stroke service in an Edinburgh teaching hospital Subjects : 417 patients with an acute stroke in the previous 30 days r and omly allocated to be contacted by a stroke family care worker ( 210 ) or to receive st and ard care ( 207 ) . The patients represented 67 % of all stroke patients assessed at the hospital during the study period . Main outcome measures : Patient completed Barthel index , Frenchay activities index , general health question naire , hospital anxiety and depression scale , social adjustment scale , mental adjustment to stroke scale , and patient satisfaction question naire ; carer completed Frenchay activities index , general health question naire , hospital anxiety and depression scale , social adjustment scale , caregiving hassles scale , and carer satisfaction question naire . Results : The groups were balanced for all important baseline variables . There were no significant differences in physical outcomes in patients or carers , though patients in the treatment group were possibly more helpless , less well adjusted socially , and more depressed , whereas carers in the treatment group were possibly less hassled and anxious . However , both patients and carers in the group contacted by the stroke family care worker expressed significantly greater satisfaction with certain aspects of their care , in particular those related to communication and support . Conclusions : The introduction of a stroke family care worker improved patients ' and their carers ' satisfaction with services and may have had some effect on psychological and social outcomes but did not improve measures of patients ' physical wellbeing . Key messages A stroke family care worker in the context of a well organised hospital based stroke service has no definite beneficial effect on the physical , social , or psychological outcome of patients or their carers A stroke family care worker may reduce carers ' hassles and anxiety but render patients more helpless , less well socially adjusted , and more depressed A stroke family care worker may improve patients ' and their carers ' satisfaction with those aspects of stroke services relating to communication and support Purchasers of health care need to decide the value they and their patients place on satisfaction with health BACKGROUND Breast cancer screening with mammography is an effective intervention for women aged 50 to 75 years but it is underused , especially by the urban poor . OBJECTIVE To improve mammography completion rates for urban women aged 52 to 77 years who had not had a mammogram in at least 2 years . METHODS We conducted a r and omized controlled trial of a case management intervention by culturally sensitive community health educators vs usual care in 6 primary care practice s supported by a computerized clinical information system . RESULTS Women in the intervention group were nearly 3 times as likely to receive a mammogram ( relative risk , 2.87 ; 95 % confidence interval , 1.75 - 4.73 ) . The benefit persisted when analyzed by age ; race , and prior screening behavior . This intervention was practice based , not dependent on visits , and enhanced the efficacy of an already successful computerized preventive care information system . CONCLUSIONS Personalized education and case management are successful in enhancing compliance with breast cancer screening among historically noncompliant vulnerable urban women . This intervention , when combined with a preventive care information system , has the potential to achieve Healthy People 2000 objectives for breast cancer screening IMPORTANCE Substance use is a major driver of the HIV epidemic and is associated with poor HIV care outcomes . Patient navigation ( care coordination with case management ) and the use of financial incentives for achieving predetermined outcomes are interventions increasingly promoted to engage patients in substance use disorders treatment and HIV care , but there is little evidence for their efficacy in improving HIV-1 viral suppression rates . OBJECTIVE To assess the effect of a structured patient navigation intervention with or without financial incentives to improve HIV-1 viral suppression rates among patients with elevated HIV-1 viral loads and substance use recruited as hospital in patients . DESIGN , SETTING , AND PARTICIPANTS From July 2012 through January 2014 , 801 patients with HIV infection and substance use from 11 hospitals across the United States were r and omly assigned to receive patient navigation alone ( n = 266 ) , patient navigation plus financial incentives ( n = 271 ) , or treatment as usual ( n = 264 ) . HIV-1 plasma viral load was measured at baseline and at 6 and 12 months . INTERVENTIONS Patient navigation included up to 11 sessions of care coordination with case management and motivational interviewing techniques over 6 months . Financial incentives ( up to $ 1160 ) were provided for achieving targeted behaviors aim ed at reducing substance use , increasing engagement in HIV care , and improving HIV outcomes . Treatment as usual was the st and ard practice at each hospital for linking hospitalized patients to outpatient HIV care and substance use disorders treatment . MAIN OUTCOMES AND MEASURES The primary outcome was HIV viral suppression ( ≤200 copies/mL ) relative to viral nonsuppression or death at the 12-month follow-up . RESULTS Of 801 patients r and omized , 261 ( 32.6 % ) were women ( mean [ SD ] age , 44.6 years [ 10.0 years ] ) . There were no differences in rates of HIV viral suppression versus nonsuppression or death among the 3 groups at 12 months . Eighty-five of 249 patients ( 34.1 % ) in the usual-treatment group experienced treatment success compared with 89 of 249 patients ( 35.7 % ) in the navigation-only group for a treatment difference of 1.6 % ( 95 % CI , -6.8 % to 10.0 % ; P = .80 ) and compared with 98 of 254 patients ( 38.6 % ) in the navigation-plus-incentives group for a treatment difference of 4.5 % ( 95 % CI -4.0 % to 12.8 % ; P = .68 ) . The treatment difference between the navigation-only and the navigation-plus-incentives group was -2.8 % ( 95 % CI , -11.3 % to 5.6 % ; P = .68 ) . CONCLUSIONS AND RELEVANCE Among hospitalized patients with HIV infection and substance use , patient navigation with or without financial incentives did not have a beneficial effect on HIV viral suppression relative to nonsuppression or death at 12 months vs treatment as usual . These findings do not support these interventions in this setting . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01612169 Objectives To test the effectiveness of a pre clinical , telephone-based patient navigation intervention to encourage colorectal cancer ( CRC ) screening among older Black men . Methods We conducted a 3-parallel-arm , r and omized trial among 731 self-identified Black men recruited at barbershops between 2010 and 2013 in New York City . Participants had to be aged 50 years or older , not be up-to- date on CRC screening , have uncontrolled high blood pressure , and have a working telephone . We r and omized participants to 1 of 3 groups : ( 1 ) patient navigation by a community health worker for CRC screening ( PN ) , ( 2 ) motivational interviewing for blood pressure control by a trained counselor ( MINT ) , or ( 3 ) both interventions ( PLUS ) . We assessed CRC screening completion at 6-month follow-up . Results Intent-to-treat analysis revealed that participants in the navigation interventions were significantly more likely than those in the MINT-only group to be screened for CRC during the 6-month study period ( 17.5 % of participants in PN , 17.8 % in PLUS , 8.4 % in MINT ; P < .01 ) . Conclusions Telephone-based pre clinical patient navigation has the potential to be effective for older Black men . Our results indicate the importance of community-based health interventions for improving health among minority men PURPOSE Health coaching by medical assistants could be a financially viable model for providing self-management support in primary care if its effectiveness were demonstrated . We investigated whether in-clinic health coaching by medical assistants improves control of cardiovascular and metabolic risk factors when compared with usual care . METHODS We conducted a 12-month r and omized controlled trial of 441 patients at 2 safety net primary care clinics in San Francisco , California . The primary outcome was a composite measure of being at or below goal at 12 months for at least 1 of 3 uncontrolled conditions at baseline as defined by hemoglobin A1c , systolic blood pressure , and low-density lipoprotein ( LDL ) cholesterol . Secondary outcomes were meeting all 3 goals and meeting individual goals . Data were analyzed using χ2 tests and linear regression models . RESULTS Participants in the coaching arm were more likely to achieve both the primary composite measure of 1 of the clinical goals ( 46.4 % vs 34.3 % , P = .02 ) and the secondary composite measure of reaching all clinical goals ( 34.0 % vs 24.7 % , P = .05 ) . Almost twice as many coached patients achieved the hemoglobin A1c goal ( 48.6 % vs 27.6 % , P = .01 ) . At the larger study site , coached patients were more likely to achieve the LDL cholesterol goal ( 41.8 % vs 25.4 % , P = .04 ) . The proportion of patients meeting the systolic blood pressure goal did not differ significantly . CONCLUSIONS Medical assistants serving as in-clinic health coaches improved control of hemoglobin A1c and LDL levels , but not blood pressure , compared with usual care . Our results highlight the need to underst and the relationship between patients ’ clinical conditions , interventions , and the context ual features of implementation BACKGROUND Screening decreases colorectal cancer ( CRC ) incidence and mortality , yet almost half of age-eligible patients are not screened at recommended intervals . OBJECTIVE To determine whether interventions using electronic health records ( EHRs ) , automated mailings , and stepped increases in support improve CRC screening adherence over 2 years . DESIGN 4-group , parallel- design , r and omized , controlled comparative effectiveness trial with concealed allocation and blinded outcome assessment s. ( Clinical Trials.gov : NCT00697047 ) SETTING 21 primary care medical centers . PATIENTS 4675 adults aged 50 to 73 years not current for CRC screening . INTERVENTION Usual care , EHR-linked mailings ( " automated " ) , automated plus telephone assistance ( " assisted " ) , or automated and assisted plus nurse navigation to testing completion or refusal ( " navigated " ) . Interventions were repeated in year 2 . MEASUREMENTS The proportion of participants current for screening in both years , defined as colonoscopy or sigmoidoscopy ( year 1 ) or fecal occult blood testing ( FOBT ) in year 1 and FOBT , colonoscopy , or sigmoidoscopy ( year 2 ) . RESULTS Compared with those in the usual care group , participants in the intervention groups were more likely to be current for CRC screening for both years with significant increases by intensity ( usual care , 26.3 % [ 95 % CI , 23.4 % to 29.2 % ] ; automated , 50.8 % [ CI , 47.3 % to 54.4 % ] ; assisted , 57.5 % [ CI , 54.5 % to 60.6 % ] ; and navigated , 64.7 % [ CI , 62.5 % to 67.0 % ] ; P < 0.001 for all pair-wise comparisons ) . Increases in screening were primarily due to increased uptake of FOBT being completed in both years ( usual care , 3.9 % [ CI , 2.8 % to 5.1 % ] ; automated , 27.5 % [ CI , 24.9 % to 30.0 % ] ; assisted , 30.5 % [ CI , 27.9 % to 33.2 % ] ; and navigated , 35.8 % [ CI , 33.1 % to 38.6 % ] ) . LIMITATION Participants were required to provide verbal consent and were more likely to be white and to participate in other types of cancer screening , limiting generalizability . CONCLUSION Compared with usual care , a central ized , EHR-linked , mailed CRC screening program led to twice as many persons being current for screening over 2 years . Assisted and navigated interventions led to smaller but significant stepped increases compared with the automated intervention only . The rapid growth of EHRs provides opportunities for spreading this model broadly |
12,876 | 28,557,246 | CONCLUSIONS Calorie restriction is associated with reduced food cravings supporting a de-conditioning model of craving reductions . | BACKGROUND Multiple studies have concluded that calorie restriction for at least 12 weeks is associated with reduced food cravings , while others have shown that calorie restriction may increase food cravings .
We addressed this ambiguity in a systematic review and meta- analysis . | BACKGROUND Although dietary restriction often results in initial weight loss , the majority of obese dieters fail to maintain their reduced weight . Diet-induced weight loss results in compensatory increase of hunger , craving and decreased ghrelin suppression that encourage weight regain . A high protein and carbohydrate breakfast may overcome these compensatory changes and prevent obesity relapse . METHODS In this study 193 obese ( BMI 32.2±1.0kg/m(2 ) ) , sedentary non diabetic adult men and women ( 47±7years ) were r and omized to a low carbohydrate breakfast ( LCb ) or an isocaloric diet with high carbohydrate and protein breakfast ( HCPb ) . Anthropometric measures were assessed every 4weeks . Fasting glucose , insulin , ghrelin , lipids , craving scores and breakfast meal challenge assessing hunger , satiety , insulin and ghrelin responses , were performed at baseline , after a Diet Intervention Period ( Week 16 ) and after a Follow-up Period ( Week 32 ) . RESULTS At Week 16 , groups exhibited similar weight loss : 15.1±1.9 kg in LCb group vs. 13.5±2.3 kg in HCPb group , p=0.11 . From Week 16 to Week 32 , LCb group regained 11.6±2.6 kg , while the HCPb group lost additional 6.9±1.7 kg . Ghrelin levels were reduced after breakfast by 45.2 % and 29.5 % following the HCPb and LCb , respectively . Satiety was significantly improved and hunger and craving scores significantly reduced in the HCPb group vs. the LCb group . CONCLUSION A high carbohydrate and protein breakfast may prevent weight regain by reducing diet-induced compensatory changes in hunger , cravings and ghrelin suppression . To achieve long-term weight loss , meal timing and macronutrient composition must counteract these compensatory mechanisms which encourage weight regain after weight loss BACKGROUND Energy or calorie restriction ( CR ) has consistently been shown to produce weight loss and have beneficial health effects in numerous species , including primates and humans . Most individuals , however , are unable to sustain weight losses induced through reductions in energy intake , potentially due to increased hunger levels . The effects that prolonged CR has on subjective aspects of appetite have not been well studied . Thus , the present study tested the effect of 6 months of caloric restriction on appetite in healthy , overweight men and women . METHODS Forty-eight overweight men and women with a body mass index ( BMI ; kg m(-2 ) ) between 25 - 29.9 took part in a 6-month study and were r and omised into one of four groups : healthy diet ( control ) ; 25 % CR ; 12.5 % CR plus exercise ( 12.5 % increased energy expenditure ; CR + EX ) ; low-calorie diet [ LCD ; 3724 kJ day(-1 ) ( 890 kcal day(-1 ) ) until 15 % of initial body weight was lost , then maintenance ] . Appetite markers ( i.e. hunger , fullness , desire to eat , etc . ) were assessed weekly during a fasting state . RESULTS Body weight was significantly reduced in all three energy-restricted groups ( CR = -10.4 + /- 0.9 % ; CR + EX = -10.0 + /- 0.8 % ; and LCD = -13.9 + /-0.7 % ) , indicating that participants were adherent to their energy restriction regimen , whereas the healthy diet control group remained weight stable ( control = -1.0 + /- 1.1 % ) . Despite these significant weight losses , appetite ratings of participants in the three energy-restricted groups at month 6 were similar to the weight stable control group . CONCLUSIONS CR regimens with low fat diets producing significant weight losses have similar effects on appetite markers over a 6-month time period compared to a weight stable control group Few well-controlled trials have evaluated the effects that macronutrient composition has on changes in food cravings during weight loss treatment . The present study , which was part of the Preventing Overweight Using Novel Dietary Strategies ( POUNDS LOST ) trial , investigated whether the fat and protein content of four different diets affected changes in specific food cravings in overweight and obese adults . A sample of 811 adults were recruited across two clinical sites , and each participant was r and omly assigned to one of four macronutrient prescriptions : 1 ) low fat ( 20 % of energy ) , average protein ( 15 % of energy ) ; 2 ) moderate fat ( 40 % ) , average protein ( 15 % ) ; 3 ) low fat ( 20 % ) , high protein ( 25 % ) ; 4 ) moderate fat ( 40 % ) , high protein ( 25 % ) . With few exceptions , the type of diet that participants were assigned did not differentially affect changes in specific food cravings . Participants assigned to the high-fat diets , however , had reduced cravings for carbohydrates at month 12 ( p<0.05 ) and fruits and vegetables at month 24 . Also , participants assigned to high-protein diets had increased cravings for sweets at month 6 and month 12 ( ps<0.05 ) . Participants in all four dietary conditions reported significant reductions in food cravings for specific types of foods ( i.e. , high fat foods , fast food fats , sweets , and carbohydrates/starches ; all ps<0.05 ) . Cravings for fruits and vegetables , however , were increased at month 24 ( p<0.05 ) . Calorically restricted diets ( regardless of their macronutrient composition ) yielded significant reductions in cravings for fats , sweets , and starches whereas cravings for fruits and vegetables were increased Behavioral studies have suggested that food cues have stronger motivating effects in obese than in normal-weight individuals , which may be a risk factor underlying obesity . Previous cross-sectional neuroimaging studies have suggested that this difference is mediated by increased reactivity to food cues in parts of the reward system in obese individuals . To date , however , only a few prospect i ve neuroimaging studies have been conducted to examine whether individual differences in brain activation elicited by food cues can predict differences in weight change . We used functional magnetic resonance imaging ( fMRI ) to investigate activation in reward-system as well as other brain regions in response to viewing high-calorie food vs. control pictures in 25 obese individuals before and after a 12-week psychosocial weight-loss treatment and at 9-mo follow-up . In those obese individuals who were least successful in losing weight during the treatment , we found greater pre-treatment activation to high-calorie food vs. control pictures in brain regions implicated in reward-system processes , such as the nucleus accumbens , anterior cingulate , and insula . We found similar correlations with weight loss in brain regions implicated by other studies in vision and attention , such as superior occipital cortex , inferior and superior parietal lobule , and prefrontal cortex . Furthermore , less successful weight maintenance at 9-mo follow-up was predicted by greater post-treatment activation in such brain regions as insula , ventral tegmental area , putamen , and fusiform gyrus . In summary , we found that greater activation in brain regions mediating motivational and attentional salience of food cues in obese individuals at the start of a weight-loss program was predictive of less success in the program and that such activation following the program predicted poorer weight control over a 9-mo follow-up period Objective Very-low-calorie diets have been shown to produce dramatic improvements in glycemic control in obese subjects with non-insulin-dependent ( type II ) diabetes . There have been no studies of the psychological responses of diabetic subjects to these diets . Research Design and Methods This study examined changes in hunger , depression , and anxiety in 33 obese type II diabetic subjects who were r and omly assigned to behavior modification programs that used either a balanced diet of 4185–6277 J∕day ( 1000–1500 cal∕day ) throughout or included an 8-wk period of a very-low-calorie diet ( 1674 J∕day or 400 cal∕day of lean meat , fish , or fowl ) . Subjects completed the Beck Depression Inventory , the Spielberger State Anxiety Question naire , and self-report measures of hunger frequently throughout the 20-wk program . Results Both groups experienced significant improvements in depressive symptomatology , anxiety , and lessening of hunger during the course of the program , with no significant differences observed between the balanced diet and the very-low-calorie diet groups . Conclusions Very-low-calorie diets , used in the context of a behavioral weight-control program , result in reductions in hunger and improvements in mood state comparable to those observed on more moderate weight-loss regimens Objective Few studies have examined brain changes in response to effective weight loss ; none have compared different methods of weight-loss intervention . We compared functional brain changes associated with a behavioral weight loss intervention to those associated with bariatric surgery . Methods 15 obese participants were recruited prior to adjustable gastric b and ing surgery and 16 obese participants were recruited prior to a behavioral diet intervention . Groups were matched for demographics and amount of weight lost . fMRI scans ( visual food motivation paradigm while hungry and following a meal ) were conducted before , and 12 weeks after surgery/behavioral intervention . Results When compared to bariatric patients in the pre-meal analyses , behavioral dieters showed increased activation to food images in right medial PFC and left precuneus following weight loss . When compared to behavioral dieters , bariatric patients showed increased activation in in bilateral temporal cortex following the weight loss . Conclusions Behavioral dieters showed increased responses to food cues in medial PFC – a region associated with valuation and processing of self-referent information – when compared to bariatric patients . Bariatric patients showed increased responses to food cues in brain regions associated with higher level perception — when compared to behavioral dieters . The method of weight loss determines unique changes in brain function This study compared reports of appetite and symptoms in 28 obese subjects r and omly assigned to either a 500 calorie protein-sparing modified fast ( PSMF ) or a 1200-kcal balanced diet . During the first comparison month , subjects consuming the PSMF lost significantly more weight and reported significantly less hunger than did subjects consuming the 1200 kcal diet . Similar results were obtained for the second month , but differences in hunger were not statistically significant . There were no significant differences between conditions in subjects ' ratings of their preoccupation with eating or in their ratings of the acceptability or disruptiveness of their diets . PSMF subjects reported significantly greater problems with cold intolerance , constipation , dizziness , dry skin , and fatigue . These symptoms remitted completely , however , when PSMF subjects consumed a 1200-kcal balanced diet . There were no significant differences between conditions in subjects ' reports of psychological functioning . Results are discussed in terms of the need for further research to identify the characteristics of PSMF which confer anorexia The importance of hunger state for the acquisition and expression of chocolate craving was investigated . Seventeen chocolate cravers and 12 non-cravers were supplied with chocolate and instructed to eat some twice a day for 14 days . Within each group , subjects were allocated to one of two conditions , hungry- or full-trained . Hungry-trained subjects were asked to eat the chocolate exclusively at least 2 h after last eating ; full-trained subjects were asked only to eat the chocolate 15 - 30 min after eating a meal . A diary was kept to encourage and allow assessment of compliance . At the start and end of the 2 weeks , subjects rated their craving for and anticipated intake of chocolate prior to eating it ; then , on initial tasting , pleasantness of the taste was rated . All subjects made these ratings on one day when hungry and on another when full , as defined above . For cravers and non-cravers who ate chocolate exclusively when hungry , chocolate craving increased post-training , but , at least for cravers , only when ratings were made while hungry . For full-trained subjects , chocolate craving decreased post-training , but this decrease did not depend on whether subjects were currently hungry or full . A similar pattern of results was found for anticipated intake and pleasantness of taste , except that pleasantness did not increase in hungry-trained subjects . The results are interpreted with reference to learned control of appetite and in particular to recent findings on incentive learning processes . Craving for chocolate or other foods may be an expression of a strong appetite elicited by hunger that has been acquired by repeated experience of eating the craved food when hungry We examined the association of food cravings with weight loss and eating behaviors in a lifestyle intervention for weight loss in worksites . This research was part of a r and omized controlled trial of a 6-month weight loss intervention versus a wait-listed control in 4 Massachusetts worksites . The intervention emphasized reducing energy intake by adherence to portion-controlled menu suggestions , and assessment s were obtained in 95 participants at baseline and 6 months including non-fasting body weight , food cravings ( Craving Inventory and Food Craving Question naire for state and trait ) and the eating behavior constructs restraint , disinhibition and hunger ( Eating Inventory ) . There were statistically significant reductions in all craving variables in the intervention group compared to the controls . Within the intervention group , changes in craving-trait were significantly associated with weight loss after controlling for baseline weight , age , gender and worksite . However , in a multivariate model with craving-trait and eating behaviors ( restraint , disinhibition and hunger ) , hunger was the only significant predictor of weight change . In contrast to some previous reports of increased food cravings with weight loss in lifestyle interventions , this study observed a broad reduction in cravings associated with weight loss . In addition , greater reductions in craving-trait were associated with greater weight change , but craving-trait was not a significant independent correlate of weight change when hunger was included in statistical models . Studies are needed to examine the effectiveness of hunger suppressing versus craving-suppressing strategies in lifestyle interventions for obesity The study objective was to evaluate the effect of prescribing a low-carbohydrate diet ( LCD ) and a low-fat diet ( LFD ) on food cravings , food preferences , and appetite . Obese adults were r and omly assigned to a LCD ( n = 134 ) or a LFD ( n = 136 ) for 2 years . Cravings for specific types of foods ( sweets , high-fats , fast-food fats , and carbohydrates/starches ) ; preferences for high-sugar , high-carbohydrate , and low-carbohydrate/high-protein foods ; and appetite were measured during the trial and evaluated during this secondary analysis of trial data . Differences between the LCD and LFD on change in outcome variables were examined with mixed linear models . Compared to the LFD , the LCD had significantly larger decreases in cravings for carbohydrates/starches and preferences for high-carbohydrate and high-sugar foods . The LCD group reported being less bothered by hunger compared to the LFD group . Compared to the LCD group , the LFD group had significantly larger decreases in cravings for high-fat foods and preference for low-carbohydrate/high-protein foods . Men had larger decreases in appetite ratings compared to women . Prescription of diets that promoted restriction of specific types of foods result ed in decreased cravings and preferences for the foods that were targeted for restriction . The results also indicate that the LCD group was less bothered by hunger compared to the LFD group and that men had larger reductions in appetite compared to women It is commonly believed that dieting and the restriction of specific types of foods produces cravings for these foods . This study , therefore , compared changes in self-reported cravings experienced by 93 obese subjects with Type II diabetes who were r and omly assigned to behavioral treatment programmes which used either : ( a ) a balanced , low-calorie diet ( LCD ) of 1000 - 1200 kcal/day throughout , with all foods allowed in moderation , or ( b ) a programme which included a 12-week period of a very low calorie diet ( VLCD ) , where intake was restricted to 400 kcal/day with only lean meat , fish , or fowl allowed . There were significant decreases in cravings for all types of foods over the 20 weeks of the study for both the VLCD and the LCD conditions . The decreases in cravings were particularly pronounced for the VLCD condition for low-fat , high-protein foods ( the only foods allowed on the VLCD ) and for complex carbohydrates , especially grains ( one of the types of foods prohibited on this diet ) . There was no evidence to support the belief that restricting intake of certain foods leads to increased craving for these foods or that the magnitude of weight loss is related to food cravings BACKGROUND Although therapeutic diets are critical to diabetes management , their acceptability to patients is largely unstudied . OBJECTIVE To quantify adherence and acceptability for two types of diets for diabetes . DESIGN Controlled trial conducted between 2004 and 2006 . SUBJECTS/ SETTING Individuals with type 2 diabetes ( n=99 ) at a community-based research facility . Participants were r and omly assigned to a diet following 2003 American Diabetes Association guidelines or a low-fat , vegan diet for 74 weeks . MAIN OUTCOME MEASURES Attrition , adherence , dietary behavior , diet acceptability , and cravings . STATISTICAL ANALYSES For nutrient intake and question naire scores , t tests determined between-group differences . For diet-acceptability measures , the related sample s Wilcoxon sum rank test assessed within-group changes ; the independent sample s Mann-Whitney U test compared the diet groups . Changes in reported symptoms among the groups was compared using chi(2 ) for independent sample s. RESULTS All participants completed the initial 22 weeks ; 90 % ( 45/50 ) of American Diabetes Association guidelines diet group and 86 % ( 42/49 ) of the vegan diet group participants completed 74 weeks . Fat and cholesterol intake fell more and carbohydrate and fiber intake increased more in the vegan group . At 22 weeks , group-specific diet adherence criteria were met by 44 % ( 22/50 ) of members of the American Diabetes Association diet group and 67 % ( 33/49 ) of vegan-group participants ( P=0.019 ) ; the American Diabetes Association guidelines diet group reported a greater increase in dietary restraint ; this difference was not significant at 74 weeks . Both groups reported reduced hunger and reduced disinhibition . Question naire responses rated both diets as satisfactory , with no significant differences between groups , except for ease of preparation , for which the 22-week ratings marginally favored the American Diabetes Association guideline group . Cravings for fatty foods diminished more in the vegan group at 22 weeks , with no significant difference at 74 weeks . CONCLUSIONS Despite its greater influence on macronutrient intake , a low-fat , vegan diet has an acceptability similar to that of a more conventional diabetes diet . Acceptability appears to be no barrier to its use in medical nutrition therapy BACKGROUND Despite increasing public health concerns regarding obesity , few safe and effective drug treatments are available . Combination treatment with sustained-release naltrexone and bupropion was developed to produce complementary actions in CNS pathways regulating bodyweight . The Contrave Obesity Research I ( COR-I ) study assessed the effect of such treatment on bodyweight in overweight and obese participants . METHODS Men and women aged 18 - 65 years who had a body-mass index ( BMI ) of 30 - 45 kg/m(2 ) and uncomplicated obesity or BMI 27 - 45 kg/m(2 ) with dyslipidaemia or hypertension were eligible for enrolment in this r and omised , double-blind , placebo-controlled , phase 3 trial undertaken at 34 sites in the USA . Participants were prescribed mild hypocaloric diet and exercise and were r and omly assigned in a 1:1:1 ratio to receive sustained-release naltrexone 32 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets ( also known as NB32 ) , sustained-release naltrexone 16 mg per day plus sustained-release bupropion 360 mg per day combined in fixed-dose tablets ( also known as NB16 ) , or matching placebo twice a day , given orally for 56 weeks . The trial included a 3-week dose escalation . R and omisation was done by use of a central ised , computer-generated , web-based system and was stratified by study centre . Co- primary efficacy endpoints at 56 weeks were percentage change in bodyweight and proportion of participants who achieved a decrease in bodyweight of 5 % or more . The primary analysis included all r and omised participants with a baseline weight measurement and a post-baseline weight measurement while on study drug ( last observation carried forward ) . This study is registered with Clinical Trials.gov , number NCT00532779 . FINDINGS 1742 participants were enrolled and r and omised to double-blind treatment ( naltrexone 32 mg plus bupropion , n=583 ; naltrexone 16 mg plus bupropion , n=578 ; placebo , n=581 ) . 870 ( 50 % ) participants completed 56 weeks of treatment ( n=296 ; n=284 ; n=290 , respectively ) and 1453 ( 83 % ) were included in the primary analysis ( n=471 ; n=471 ; n=511 ) . Mean change in bodyweight was -1.3 % ( SE 0.3 ) in the placebo group , -6.1 % ( 0.3 ) in the naltrexone 32 mg plus bupropion group ( p<0.0001 vs placebo ) and -5.0 % ( 0.3 ) in the naltrexone 16 mg plus bupropion group ( p<0.0001 vs placebo ) . 84 ( 16 % ) participants assigned to placebo had a decrease in bodyweight of 5 % or more compared with 226 ( 48 % ) assigned to naltrexone 32 mg plus bupropion ( p<0.0001 vs placebo ) and 186 ( 39 % ) assigned to naltrexone 16 mg plus bupropion ( p<0.0001 vs placebo ) . The most frequent adverse event in participants assigned to combination treatment was nausea ( naltrexone 32 mg plus bupropion , 171 participants [ 29.8 % ] ; naltrexone 16 mg plus bupropion , 155 [ 27.2 % ] ; placebo , 30 [ 5.3 % ] ) . Headache , constipation , dizziness , vomiting , and dry mouth were also more frequent in the naltrexone plus bupropion groups than in the placebo group . A transient increase of around 1.5 mm Hg in mean systolic and diastolic blood pressure was followed by a reduction of around 1 mm Hg below baseline in the naltrexone plus bupropion groups . Combination treatment was not associated with increased depression or suicidality events compared with placebo . INTERPRETATION A sustained-release combination of naltrexone plus bupropion could be a useful therapeutic option for treatment of obesity . FUNDING Orexigen Therapeutics CONTEXT Lorcaserin , a selective 5-hydroxytryptamine (5-HT)(2C ) receptor agonist , reduces body weight . It is unclear whether weight loss is due to reduced energy intake ( EI ) or also to enhanced energy expenditure ( EE ) . OBJECTIVE This study tested the effect of lorcaserin on EI and EE . DESIGN , PARTICIPANTS , AND INTERVENTION In a double-blind , r and omized , placebo-controlled trial , 57 ( 39 women ) overweight and obese ( body mass index , 27 - 45 kg/m(2 ) ) adults were r and omized to placebo ( n = 28 ) or 10 mg twice daily lorcaserin ( n = 29 ) for 56 d. Weight maintenance was imposed during d 1 - 7 . Beginning on d 8 , participants followed a diet and exercise plan targeting a 600 kcal/d deficit . OUTCOMES At baseline and after 7 and 56 d of treatment , we measured body weight , body composition ( dual x-ray absorptiometry ) , blood pressure , heart rate , EI at lunch and dinner , subjective appetite ratings , and 24-h EE and 24-h-respiratory quotient ( RQ ) , measured by indirect calorimetry in a respiratory chamber . RESULTS After 7 d of weight maintenance , EI was significantly ( P < 0.01 ) reduced with lorcaserin but not placebo ( mean ± sem for lorcaserin , -286 ± 86 kcal ; placebo , -147 ± 89 kcal ) . After 56 d , lorcaserin result ed in significantly larger reductions in body weight ( lorcaserin , -3.8 ± 0.4 kg ; placebo , -2.2 ± 0.5 kg ; P < 0.01 ) , EI ( lorcaserin , -470 ± 87 kcal ; placebo , -205 ± 91 kcal ; P < .05 ) , and appetite ratings than in placebo . Changes in 24-h EE and 24-h RQ did not differ between groups , even after 24-h EE was adjusted for body weight and composition . Compared with placebo , lorcaserin had no effect on systolic or diastolic blood pressure or heart rate after 56 d. CONCLUSIONS Lorcaserin reduces body weight through reduced EI , not altered EE or RQ Objective : To examine characteristics of craved foods in relation to dietary energy restriction ( ER ) with high ( HG ) and low glycemic load ( LG ) diets . Design : Assessment s of food cravings before and during a r and omized controlled trial of HG and LG diets provided for 6 months . Subjects : Thirty-two healthy , overweight women aged 20–42 years . Measurements : Self-reported food cravings and dietary intake , body weight , weight history and measures of eating behaviors . Results : Foods craved at baseline were more than twice as high in energy density as the habitual diet ( 3.7±1.5 vs 1.7±0.3 kcal/g ; P<0.001 ) , and on average were lower in protein ( P<0.001 ) and fiber ( P<0.001 ) and higher in fat ( P=0.002 ) . There were no statistically significant changes in nutritional characteristics of craved foods after 6 months of ER . There was a significant relationship between reported portion size of craved food consumed at baseline and lifetime high body mass index ( r=0.49 , P=0.005 ) . Additionally , there was a significant association between susceptibility to hunger and craving frequency at baseline , and there were significant relationships between hunger score , craving frequency , strength and percentage of time that cravings are given in to after 6 months of ER . In multiple regression models , subjects who lost a greater percentage of weight craved higher energy-dense foods at month 6 of ER , but also reported giving in to food cravings less frequently ( adjusted R 2=0.31 , P=0.009 ) . Conclusion : High energy density and fat content , and low protein and fiber contents were identifying characteristics of craved foods . The relationships between craving variables and hunger score suggest that the relative influence of hunger susceptibility on cravings may be important before and especially after ER . Portion size of craved foods and frequency of giving in to food cravings appear to be important areas for focus in lifestyle modification programs for long-term weight loss |
12,877 | 23,674,441 | This analysis failed to confirm an association between dietary ALA intake and prostate cancer risk . | OBJECTIVE α-Linolenic acid ( ALA ) is considered to be a cardioprotective nutrient ; however , some epidemiological studies have suggested that dietary ALA intake increases the risk of prostate cancer .
The main objective was to conduct a systematic review and meta- analysis of case-control and prospect i ve studies investigating the association between dietary ALA intake and prostate cancer risk . | We prospect ively investigated the associations between dietary patterns and risk of prostate cancer in the Health Professionals Follow-up Study . Between 1986 and 2000 , 3,002 incident prostate cancer cases were identified in our cohort . Using factor analysis , two major dietary patterns were identified , a prudent and a western dietary pattern . Dietary patterns were not appreciably associated with risk of total prostate cancer . For the highest versus the lowest quintiles , the multivariable relative risk ( RR ) for the prudent pattern was 0.94 [ 95 % confidence interval ( CI ) , 0.83 - 1.06 ] , and for the western pattern , the multivariable RR was 1.03 ( 95 % CI , 0.92 - 1.17 ) . Neither were these associated with risk of advanced prostate cancer [ highest versus lowest quintile , prudent pattern ( RR , 1.01 ; 95 % CI , 0.68 - 1.49 ) ; western pattern ( RR , 1.13 ; 95 % CI , 0.77 - 1.67 ) ] . Higher western pattern scores were suggestively associated with a greater risk of advanced prostate cancer among older men [ highest versus lowest quintile ( RR , 1.35 ; 95 % CI , 0.97 - 1.90 ) ] , but not after adding processed meat to the model [ highest versus lowest quintile ( RR , 1.11 ; 95 % CI , 0.75 - 1.65 ) ] . We did not find any evidence for a protective association between prudent pattern and risk of prostate cancer . The lack of association between a western dietary pattern as identified by factor analysis in our cohort and prostate cancer risk suggests that dietary risk factors for prostate cancer are likely to differ from those for other conditions , such as cardiovascular disease and type 2 diabetes , that have been associated with a western dietary pattern in this cohort . ( Cancer Epidemiol Biomarkers Prev 2006;15(1):167–71 BACKGROUND Laboratory studies have shown that n-3 fatty acids inhibit and n-6 fatty acids stimulate prostate tumor growth , but whether the dietary intake of these fatty acids affects prostate cancer risk in humans remains unclear . OBJECTIVE We prospect ively evaluated the association between intakes of alpha-linolenic ( ALA ; 18:3n-3 ) , eicosapentaenoic ( EPA ; 20:5n-3 ) , docosahexaenoic ( DHA ; 22:6n-3 ) , linoleic ( LA ; 18:2n-6 ) , and arachidonic ( AA ; 20:4n-6 ) acids and prostate cancer risk . DESIGN A cohort of 47 866 US men aged 40 - 75 y with no cancer history in 1986 was followed for 14 y. RESULTS During follow-up , 2965 new cases of total prostate cancer were ascertained , 448 of which were advanced prostate cancer . ALA intake was unrelated to the risk of total prostate cancer . In contrast , the multivariate relative risks ( RRs ) of advanced prostate cancer from comparisons of extreme quintiles of ALA from nonanimal sources and ALA from meat and dairy sources were 2.02 ( 95 % CI : 1.35 , 3.03 ) and 1.53 ( 0.88 , 2.66 ) , respectively . EPA and DHA intakes were related to lower prostate cancer risk . The multivariate RRs of total and advanced prostate cancer from comparisons of extreme quintiles of the combination of EPA and DHA were 0.89 ( 0.77 , 1.04 ) and 0.74 ( 0.49 , 1.08 ) , respectively . LA and AA intakes were unrelated to the risk of prostate cancer . The multivariate RR of advanced prostate cancer from a comparison of extreme quintiles of the ratio of LA to ALA was 0.62 ( 0.45 , 0.86 ) . CONCLUSIONS Increased dietary intakes of ALA may increase the risk of advanced prostate cancer . In contrast , EPA and DHA intakes may reduce the risk of total and advanced prostate cancer BACKGROUND Experimental studies in laboratory animals and humans suggest that alpha-linolenic acid ( 18:3n-3 ) may reduce the risk of arrhythmia . OBJECTIVE The objective was to examine the association between dietary intake of alpha-linolenic acid and risk of fatal ischemic heart disease ( IHD ) . DESIGN This was a prospect i ve cohort study . The intake of alpha-linolenic acid was derived from a 116-item food-frequency question naire completed in 1984 by 76283 women without previously diagnosed cancer or cardiovascular disease . RESULTS During 10 y of follow-up , we documented 232 cases of fatal IHD and 597 cases of nonfatal myocardial infa rct ion . After adjustment for age , st and ard coronary risk factors , and dietary intake of linoleic acid and other nutrients , a higher intake of alpha-linolenic acid was associated with a lower relative risk ( RR ) of fatal IHD ; the RRs from the lowest to highest quintiles were 1.0 , 0.99 , 0.90 , 0.67 , and 0.55 ( 95 % CI : 0.32 , 0.94 ; P for trend = 0.01 ) . For nonfatal myocardial infa rct ion there was only a modest , nonsignificant trend toward a reduced risk when extreme quintiles were compared ( RR : 0.85 ; 95 % CI : 0.61 , 1.19 ; P for trend = 0.50 ) . A higher intake of oil and vinegar salad dressing , an important source of alpha-linolenic acid , was associated with reduced risk of fatal IHD when women who consumed this food > or = 5 - 6 times/wk were compared with those who rarely consumed this food ( RR : 0.46 ; 95 % CI : 0.27 , 0.76 ; P for trend = 0.001 ) . CONCLUSIONS This study supports the hypothesis that a higher intake of alpha-linolenic acid is protective against fatal IHD . Higher consumption of foods such as oil-based salad dressing that provide polyunsaturated fats , including alpha-linolenic acid , may reduce the risk of fatal IHD BACKGROUND The rapid emergence of coronary artery disease ( CAD ) in south Asian people is not explained by conventional risk factors . In view of cardioprotective effects of a Mediterranean style diet rich in alpha-linolenic acid , we assessed the benefits of this diet for patients at high risk of CAD . METHODS We did a r and omised , single-blind trial in 1000 patients with angina pectoris , myocardial infa rct ion , or surrogate risk factors for CAD . 499 patients were allocated to a diet rich in whole grains , fruits , vegetables , walnuts , and almonds . 501 controls consumed a local diet similar to the step I National Cholesterol Education Program ( NCEP ) prudent diet . FINDINGS The intervention group consumed more fruits , vegetables , legumes , walnuts , and almonds than did controls ( 573 g [ SD 127 ] vs 231 g [ 19 ] per day p<0.001 ) . The intervention group had an increased intake of whole grains and mustard or soy bean oil . The mean intake of alpha-linolenic acid was two-fold greater in the intervention group ( 1.8 g [ SD 0.4 ] vs 0.8 g [ 0.2 ] per day , p<0.001 ) . Total cardiac end points were significantly fewer in the intervention group than the controls ( 39 vs 76 events , p<0.001 ) . Sudden cardiac deaths were also reduced ( 6 vs 16 , p=0.015 ) , as were non-fatal myocardial infa rct ions ( 21 vs 43 , p<0.001 ) . We noted a significant reduction in serum cholesterol concentration and other risk factors in both groups , but especially in the intervention diet group . In the treatment group , patients with pre-existing CAD had significantly greater benefits compared with such patients in the control group . INTERPRETATION An Indo-Mediterranean diet that is rich in alpha-linolenic acid might be more effective in primary and secondary prevention of CAD than the conventional step I NCEP prudent diet The role of diet in the etiology of prostate cancer remains unclear , because results from several case‐control and cohort studies on fat intake and risk of prostate cancer have been inconsistent ; few of the studies have adjusted the results for caloric intake . To examine the relationship between energy , intake of several nutrients and risk of prostate cancer ( all stages combined and advanced stages separately ) , we conducted a population ‐based case‐control study in Örebro County , Sweden , from 1989 through 1994 . A total of 526 patients with newly diagnosed prostate cancer and 536 controls , r and omly selected from the population register and frequency‐matched by age , were included in the analyses . Information about dietary intake was obtained from a self‐administered semi‐quantitative food frequency question naire . Odds ratios with 95 % confidence intervals were estimated by unconditional logistic regression . In age‐adjusted analyses , there were positive associations of prostate cancer ( all stages combined ) risk with total energy intake as well as intake of total fat ( saturated and monounsaturated ) , protein , retinol and zinc . The positive association with energy intake was stronger for advanced cancer , with an excess risk of 70 % for the highest quartile vs. the lowest . After adjustment for energy intake , there was no apparent association of prostate cancers ( all stages combined ) with any of the investigated nutrients . However , a weak positive association between intake of retinol and advanced cancer was observed . We conclude that our results provide some evidence that total energy intake is a risk factor for prostate cancer . © 1996 Wiley‐Liss , Background Alpha-linolenic acid ( ALA ) is the most common omega-3 fatty acid in the Western diet . The relation of dietary intake of ALA to prostate cancer risk remains unresolved . Objective We prospect ively evaluated total ALA and ALA from specific food sources including animal , fish , and plant sources in relation to prostate cancer risk . Design A cohort of 29,592 male participants ( age 55–74 years ) in the screening arm of the Prostate , Lung , Colorectal , and Ovarian ( PLCO ) Cancer Screening Trial was followed for an average of 5.1 years . Results We ascertained 1,898 cases of total prostate cancer , of which 1,631 were organ-confined cases ( stage T1b to T3a and N0M0 ) and 285 were advanced stage cases ( stage≥T3b , N1 , or M1 ) . We found no association between total ALA intake and overall prostate cancer ( multivariate RR comparing extreme quintiles=0.94 ; 95 % CI=0.81–1.09 ; P for trend=0.76 ) . The corresponding RRs for organ-confined and advanced prostate cancer were 0.94 ( 95 % CI=0.80–1.10 ; P for trend=0.80 ) and 0.83 ( 95 % CI=0.58–1.19 ; P for trend=0.34 ) , respectively . In addition , no relations were observed between ALA intake from any specific food source and the risks of total , organ-confined , or advanced prostate cancer . ALA intake also showed no association with low grade ( Gleason sum<7 ; 1,221 cases ) tumors ( P for trend=0.23 ) or high grade ( Gleason sum≥7 ; n=677 cases ) tumors ( P for trend=0.26 ) . Conclusions In this prospect i ve study of predominantly Caucasian men who were screened annually for newly incident prostate cancer , dietary intake of total ALA and ALA from specific food sources was not associated with risk of total prostate cancer or prostate tumors that were defined by stage and grade BACKGROUND Alpha-linolenic acid , an intermediate-chain n-3 fatty acid found primarily in plants , may decrease the risk of fatal coronary heart disease ( CHD ) through a reduction in fatal ventricular arrhythmias and sudden cardiac death ( SCD ) . METHODS AND RESULTS We prospect ively examined the association between dietary intake of alpha-linolenic acid assessed via up date d food-frequency question naires and the risk of SCD , other fatal CHD , and nonfatal myocardial infa rct ion ( MI ) among 76,763 women participating in the Nurses ' Health Study who were free from cancer and completed a dietary question naire at baseline in 1984 . During 18 years of follow-up , we identified 206 SCDs , 641 other CHD deaths , and 1604 nonfatal MIs . After controlling for coronary risk factors and other fatty acids , including long-chain n-3 fatty acids , the intake of alpha-linolenic acid was inversely associated with the risk of SCD ( P for trend , 0.02 ) but not with the risk of other fatal CHD or nonfatal MI . Compared with women in the lowest quintile of alpha-linolenic acid intake , those in the highest 2 quintiles had a 38 % to 40 % lower SCD risk . This inverse relation with SCD risk was linear and remained significant even among women with high intakes of long-chain n-3 fatty acids . CONCLUSIONS These prospect i ve data suggest that increasing dietary intake of alpha-linolenic acid may reduce the risk of SCD but not other types of fatal CHD or nonfatal MI in women . The specificity of the association between alpha-linolenic acid and SCD supports the hypothesis that these n-3 fatty acids may have antiarrhythmic properties In a r and omized , placebo-controlled trial , the effects of treatment with fish oil ( eicosapentaenoic acid , 1.08 g/day ) and mustard oil ( alpha-linolenic acid , 2.9 g/day ) were compared for 1 year in the management of 122 patients ( fish oil , group A ) , 120 patients ( mustard oil , group B ) , and 118 patients ( placebo , group C ) with suspected acute myocardial infa rct ion ( AMI ) . Treatments were administered about ( mean ) 18 hours after the symptoms of AMI in all three groups . The extent of cardiac disease , rise in cardiac enzymes , and lipid peroxides were comparable among the groups at entry into the study . After 1 year total cardiac events were significantly less in the fish oil and mustard oil groups compared with the placebo group ( 24.5 % and 28 % vs. 34.7 % , p > 0.01 ) . Nonfatal infa rct ions were also significantly less in the fish oil and mustard oil groups compared with the placebo group ( 13.0 % and 15.0 % vs. 25.4 % , p > 0.05 ) . Total cardiac deaths showed no significant reduction in the mustard oil group ; however , the fish oil group had significantly less cardiac deaths compared with the placebo group ( 11.4 % vs. 22.0 % , p > 0.05 ) . Apart from the decrease in the cardiac event rate , the fish oil and mustard oil groups also showed a significant reduction in total cardiac arrhythmias , left ventricular enlargement , and angina pectoris compared with the placebo group . Reductions in blood lipoproteins in the two intervention groups were modest and do not appear to be the cause of the benefit in the two groups . Diene conjugates showed a significant reduction in the fish oil and mustard oil groups , indicating that a part of the benefit may be caused by the reduction in oxidative stress . The findings of this study suggest that fish oil and mustard oil , possibly due to the presence of n-3 fatty acids , may provide rapid protective effects in patients with AMI . However , a large study is necessary to confirm this suggestion In vivo , in vitro , prospect i ve , and retrospective epidemiologic inquiries have suggested that retinoids inhibit cancer , and fats have been hypothesized to enhance and ascorbic acid to reduce cancer risk . Comparison of 260 patients from Buffalo with cancer of the prostate gl and was made with two different control series of similar size and age distribution . Regardless of the control group , risk of prostate cancer gained with increases in ingestion of retinoids , animal fats , and vitamin C. These anomalous findings may be due to peculiarities in methodology . From the possible specificity of effect of the nutrients studied , as shown in experimental animals and in vitro , a hypothesis could be made that a substance like vitamin A or C , which may inhibit certain cancers , also may enhance risk of other cancer types or have neither effect BACKGROUND The strong correlation between national consumption of fat and national rate of mortality from prostate cancer has raised the hypothesis that dietary fat increases the risk of this malignancy . Case-control and cohort studies have not consistently supported this hypothesis . PURPOSE We examined prospect ively the relationship between prostate cancer and dietary fat , including specific fatty acids and dietary sources of fat . We examined the relationship of fat consumption to the incidence of advanced prostate cancer ( stages C , D , or fatal cases ) and to the total incidence of prostate cancer . METHODS We used data from the Health Professionals Follow-up Study , which is a prospect i ve cohort of 51529 U.S. men , aged 40 through 75 , who completed a vali date d food-frequency question naire in 1986 . We sent follow-up question naires to the entire cohort in 1988 and 1990 to document new cases of a variety of diseases and to up date exposure information . As of January 31 , 1990 , 300 new cases of prostate cancer , including 126 advanced cases , were documented in 47855 participants initially free of diagnosed cancer . The Mantel-Haenszel summary estimator was used to adjust for age and other potentially confounding variables . Multiple logistic regression was used to estimate relative risks ( RRs ) when controlling simultaneously for more than two covariates . RESULTS Total fat consumption was directly related to risk of advanced prostate cancer ( age- and energy-adjusted RR = 1.79 , with 95 % confidence interval [ CI ] = 1.04 - 3.07 , for high versus low quintile of intake ; P [ trend ] = .06 ) . This association was due primarily to animal fat ( RR = 1.63 ; 95 % CI = 0.95 - 2.78 ; P [ trend ] = .08 ) , but not vegetable fat . Red meat represented the food group with the strongest positive association with advanced cancer ( RR = 2.64 ; 95 % CI = 1.21 - 5.77 ; P = .02 ) . Fat from dairy products ( with the exception of butter ) or fish was unrelated to risk . Saturated fat , monounsaturated fat , and alpha-linolenic acid , but not linoleic acid , were associated with advanced prostate cancer risk ; only the association with alpha-linolenic acid persisted when saturated fat , monounsaturated fat , linoleic acid , and alpha-linolenic acid were modeled simultaneously ( multivariate RR = 3.43 ; 95 % CI = 1.67 - 7.04 ; P [ trend ] = .002 ) . CONCLUSION The results support the hypothesis that animal fat , especially fat from red meat , is associated with an elevated risk of advanced prostate cancer . IMPLICATION S These findings support recommendations to lower intake of meat to reduce the risk of prostate cancer . The potential roles of carcinogens formed in cooking animal fat and of alpha-linolenic acid in the progression of prostate cancer need to be explored In a prospect i ve , r and omised single-blinded secondary prevention trial we compared the effect of a Mediterranean alpha-linolenic acid-rich diet to the usual post-infa rct prudent diet . After a first myocardial infa rct ion , patients were r and omly assigned to the experimental ( n = 302 ) or control group ( n = 303 ) . Patients were seen again 8 weeks after r and omisation , and each year for 5 years . The experimental group consumed significantly less lipids , saturated fat , cholesterol , and linoleic acid but more oleic and alpha-linolenic acids confirmed by measurements in plasma . Serum lipids , blood pressure , and body mass index remained similar in the 2 groups . In the experimental group , plasma levels of albumin , vitamin E , and vitamin C were increased , and granulocyte count decreased . After a mean follow up of 27 months , there were 16 cardiac deaths in the control and 3 in the experimental group ; 17 non-fatal myocardial infa rct ion in the control and 5 in the experimental groups : a risk ratio for these two main endpoints combined of 0.27 ( 95 % CI 0.12 - 0.59 , p = 0.001 ) after adjustment for prognostic variables . Overall mortality was 20 in the control , 8 in the experimental group , an adjusted risk ratio of 0.30 ( 95 % CI 0.11 - 0.82 , p = 0.02 ) . An alpha-linolenic acid-rich Mediterranean diet seems to be more efficient than presently used diets in the secondary prevention of coronary events and death |
12,878 | 17,562,735 | Anticonvulsants and antidepressants are still the most commonly used options to manage diabetic neuropathy .
Oral tricyclic antidepressants and traditional anticonvulsants are better for short term pain relief than newer generation anticonvulsants .
Evidence of the long term effects of oral antidepressants and anticonvulsants is still lacking . | OBJECTIVE To evaluate the effects of treatments for the symptoms of painful diabetic neuropathy . | A prospect i ve survey study was performed in patients with painful diabetic polyneuropathy ( PDN ) to assess the nature and scope of their pain . Pain associated with diabetic neuropathy is commonly encountered in clinical practice . Yet , little is known regarding the pain experience and impact on quality of life in persons with painful diabetic neuropathy . These 105 patients noted an average of 6/10 pain , most often described as ' burning ' , ' electric ' , ' sharp ' , and ' dull/ache ' , which , for most , is worse at night time and when tired or stressed . On average , patients reported that the pain caused substantial interference in sleep and enjoyment of life and moderate interference in recreational activities , normal work , mobility , general activity , social activities , and mood . Unexpectedly , a potential genetic predisposition to the development of painful neuropathy was suggested by the fact that a majority ( 56 % ) reported a family member with PDN . Thus , this study found that pain associated with diabetic neuropathy is a significant medical issue that has a substantial impact on the quality of life of many people with this condition & NA ; Levodopa has been used to treat some painful conditions and found to be effective in neuropathic pain due to herpes zoster in a double‐blind study . From our anecdotal observations about the efficacy of levodopa on diabetic neuropathic pain , we design ed a double‐blind placebo‐controlled study to test levodopa in painful diabetic neuropathy . Twenty‐five out‐ patients with painful symmetrical diabetic polyneuropathy were admitted to the study . Fourteen patients were given 100 mg levodopa plus 25 mg benserazide to be taken three times per day for 28 days . Eleven patients were given identical placebo capsules . A blinded neurologist evaluated the patients clinical ly and performed Visual Analogue Scale ( VAS ) measurement every week from day 0 to day 28 . The results seemed promising and levodopa may be a choice for the control of pain in neuropathy for which we do not have many alternative treatments BACKGROUND Both basic and clinical research has demonstrated that antiepileptic drugs can be effective in alleviating neuropathic pain . It was hypothesized that oxcarbazepine might be effective in reducing the symptoms of painful diabetic neuropathy . AIMS To investigate the long-term efficacy and safety of oxcarbazepine in symptoms of painful diabetic neuropathy . MATERIAL S AND METHODS This study included thirty-eight painful diabetic neuropathy patients , which were screened with clinical assessment and electrophysiological studies . The efficacy and safety of oxcarbazepine were evaluated according to the changes in pain intensity and social interference subitems scores of Short-form Brief Pain Inventory besides electrophysiological studies at the end of six months of the treatment . STATISTICAL ANALYSIS The Students t , Mann-Whitney U and Rank Sum test and Chi-square tests were applied to examine variables differences . The level of statistical significance was chosen to be P<0.05 . RESULTS A significant difference was found in all of subitems of pain intensity and social interference at the end of the study according to the baseline scores . Improvement was observed in 52.7 % , 63.1 % , 55.3 % and 63.2 % of patients for worst , least , average and pain right now at the end of six months , respectively . Improvement was observed as 60.6 % , 63.2 % , 52.6 % , 60.5 % , 68.4 % and 63.2 % for general activity , mood , walk , work , people relations , sleep and life enjoyment subitems , respectively . None of these patients had any prominent side effect leading to discontinue the treatment . CONCLUSION Long-term oxcarbazepine treatment was found to be effective and safe in the symptoms of painful diabetic neuropathy AIMS To determine the prevalence and risk factors for neuropathy and peripheral vascular disease ( PVD ) in the Australian diabetic population and identify those at high risk of foot ulceration . METHODS The Australian Diabetes Obesity and Lifestyle study included 11 247 adults aged > or= 25 years in 42 r and omly selected areas of Australia . Neuropathy and PVD were assessed in participants identified as having diabetes ( based on self report and oral glucose tolerance test ) , impaired fasting glucose , impaired glucose tolerance and in a r and om sample with normal glucose tolerance ( total n = 2436 ) . RESULTS The prevalence of peripheral neuropathy was 13.1 % in those with known diabetes ( KDM ) and 7.1 % in those with newly diagnosed ( NDM ) . The prevalence of PVD was 13.9 % in KDM and 6.9 % in NDM . Of those with diabetes , 19.6 % were at risk of foot ulceration . Independent risk factors for peripheral neuropathy were diabetes duration ( odds ratio ( 95 % CI ) 1.73 ( 1.33 - 2.28 ) per 10 years ) , height ( 1.42 ( 1.08 - 1.88 ) per 10 cm ) , age ( 2.57 ( 1.94 - 3.40 ) per 10 years ) and uric acid ( 1.59 ( 1.21 - 2.09 ) per 0.1 mmol/l ) . Risk factors for PVD were diabetes duration ( 1.64 ( 1.25 - 2.16 ) per 10 years ) , age ( 2.45 ( 1.86 - 3.22 ) per 10 years ) , smoking ( 2.07 ( 1.00 - 4.28 ) ) , uric acid ( 1.03 ( 1.00 - 1.06 ) per 0.1 mmol/l ) and urinary albumin/creatinine ratio ( 1.11 ( 1.01 - 1.21 ) per 1 mg/mmol ) . CONCLUSIONS The prevalence of neuropathy and PVD was lower in this population than has been reported in other population s. This may reflect differences in sampling methods between community and hospital-based population s. Nevertheless , a substantial proportion of the diabetic population had risk factors for foot ulceration BACKGROUND A cause- and -effect relation between blood glucose concentrations and microvascular complications in patients with insulin-dependent diabetes mellitus has not been established . METHODS We r and omly assigned 102 patients with insulin-dependent diabetes mellitus , nonproliferative retinopathy , normal serum creatinine concentrations , and unsatisfactory blood glucose control to intensified insulin treatment ( 48 patients ) or st and ard insulin treatment ( 54 patients ) . We then evaluated them for microvascular complications after 18 months and 3 , 5 , and 7.5 years . RESULTS Mean ( + /- SD ) glycosylated hemoglobin values were reduced from 9.5 + /- 1.3 percent to 7.1 + /- 0.7 percent in the group receiving intensified treatment and from 9.4 + /- 1.4 percent to 8.5 + /- 0.7 percent in the group receiving st and ard treatment ( P = 0.001 ) . In 12 of the patients receiving intensified treatment ( 27 percent of those included in the analysis ) and 27 of those receiving st and ard treatment ( 52 percent ) , serious retinopathy requiring photocoagulation developed ( P = 0.01 ) . Visual acuity decreased in 6 patients receiving intensified treatment ( 14 percent ) and in 18 receiving st and ard treatment ( 35 percent ) ( P = 0.02 ) . Nephropathy ( urinary albumin excretion , > 200 micrograms per minute ) developed in one patient in the group receiving intensified treatment , as compared with nine patients in the group receiving st and ard treatment ( P = 0.01 ) . No patient in the intensified-treatment group had nephropathy with subnormal glomerular filtration rates , as compared with six patients in the st and ard-treatment group ( P = 0.02 ) . The conduction velocities of the ulnar , tibial , peroneal , and sural nerves decreased significantly more in the st and ard-treatment group than in the intensified-treatment group . The odds ratio for serious retinopathy was 0.4 ( 95 percent confidence interval , 0.2 to 1.0 ; P = 0.04 ) in the intensified-treatment group as compared with the st and ard-treatment group . The corresponding odds ratio for nephropathy was 0.1 ( 95 percent confidence interval , 0 to 0.8 ; P = 0.04 ) . CONCLUSIONS Long-term intensified insulin treatment , as compared with st and ard treatment , retards the development of microvascular complications in patients with insulin-dependent diabetes mellitus AIMS /HYPOTHESIS To study similarities and differences between people with insensate or painful diabetic peripheral neuropathy , particularly in relation to height , gender , ethnicity and glycaemic control . METHODS We studied prospect ively 2610 patients with Type 2 diabetes attending our Diabetes Centre . Subjects were compared according to degree of sensory loss , and presence or absence of neuropathic pain . The effects of gender and ethnicity were evaluated by study ing patients in different height b and s. RESULTS Insensate neuropathy and painful neuropathy was present in 11.4 and 3.3 % of subjects , respectively . Age , duration of diabetes , height , vibration perception and HbA(1c ) ( P<0.0001 ) were independent determinants of insensate neuropathy , whereas only duration of diabetes and vibration perception ( P<0.0001 ) were predictive of pain . There was more insensate neuropathy in males ( OR 1.9 ) and anglo-celtics ( OR 1.4 ) but stratification by height showed that these effects were due to height . Height has no influence on the development of pain . CONCLUSIONS There is significant overlap but also considerable dichotomy in the two major forms of diabetic sensory peripheral neuropathy . The insensate type is more explainable by duration , degree of hyperglycaemia and length of peripheral nerves , factors that are likely to reflect severity of underlying structural nerve damage . Glycaemic control was not a predictor of painful neuropathy & NA ; Pregabalin binds with high affinity to the alpha2‐delta subunit protein of voltage‐gated calcium channels and , thereby , reduces release of excitatory neurotransmitters . This 12‐week r and omised , double‐blind , multicentre , placebo‐controlled , parallel‐group study evaluated the efficacy and safety of pregabalin in patients with chronic postherpetic neuralgia ( PHN ) or painful diabetic peripheral neuropathy ( DPN ) . Patients were r and omised to placebo ( n=65 ) or to one of two pregabalin regimens : a flexible schedule of 150 , 300 , 450 , and 600 mg/day with weekly dose escalation based on patients ' individual responses and tolerability ( n=141 ) or a fixed schedule of 300 mg/day for 1 week followed by 600 mg/day for 11 weeks ( n=132 ) . Both flexible‐ and fixed‐dose pregabalin significantly reduced endpoint mean pain score ( primary outcome ) versus placebo ( P=0.002 , P<0.001 ) and were significantly superior to placebo in improving pain‐related sleep interference ( P<0.001 ) . The most common adverse events ( AEs ) for pregabalin‐treated patients were dizziness , peripheral oedema , weight gain ( not affecting diabetes control ) , and somnolence . These results are consistent with previous studies ' demonstrating pregabalin 's efficacy , tolerability , and safety for treatment of chronic neuropathic pain associated with DPN or PHN . Pregabalin dosing aim ed at optimal balance of efficacy and tolerability provides significant pain relief and may reduce risks for AEs and therapy discontinuation OBJECTIVE To prove the efficacy of mexiletine in painful diabetic neuropathy . RESEARCH DESIGN AND METHODS Treatment was provided in three dosages . For pain measurements , a VAS and McGill 's verbal rating scale were chosen . Ninety-five patients were included in the study . RESULTS A global assessment of the VAS among patients showed no differences between mexiletine treatment and placebo . The total evaluation ( PRIT ) of the McGill scale fell just below the level of significance . More specific exploratory evaluations of subclasses of the McGill scale , representing different degrees of pain , gave remarkable differences between mexiletine and placebo in sensory and miscellaneous items . In special subgroups , which were formed according to types and courses of complaints compiled at the beginning of this evaluation , the substantial advantages of the mexiletine treatment were shown with both the VAS and the McGill scale . CONCLUSIONS Evidence strongly indicates that , in particular , those patients with stabbing or burning pain , heat sensations , or formication will benefit most by mexiletine therapy . Concerning the dosage , a medium regimen of 450 mg/day seems to be appropriate . With an increase in the antiarryhthmic dosage level , the efficacy does not rise proportionally . Mexiletine proved to be a safe therapy with negligible side effects at the medium dose range , even < placebo ; and remarkably , no cardiovascular side effects were noted . Further studies should avoid global assessment s and pay more attention to the variety of complaints and quality of life |
12,879 | 27,118,443 | Overall , the evidence base for interventions to improve postpartum retention in HIV care is weak .
Nevertheless , there is some evidence that phone-based interventions can improve retention in PMTCT in the first one to three months postpartum | INTRODUCTION The World Health Organization recommends lifelong antiretroviral therapy ( ART ) for all pregnant and breastfeeding women living with HIV .
Effective transitioning from maternal and child health to ART services , and long-term retention in ART care postpartum is crucial to the successful implementation of lifelong ART for pregnant women .
This systematic review aims to determine which interventions improve ( 1 ) retention within prevention of mother-to-child HIV transmission ( PMTCT ) programmes after birth , ( 2 ) transitioning from PMTCT to general ART programmes in the postpartum period , and ( 3 ) retention of postpartum women in general ART programmes . | Objective : The main aim of this study was to reduce breast-milk transmission of HIV-1 by treating HIV-1-infected women with highly active antiretroviral therapy ( HAART ) during breastfeeding . Methods : Mitra Plus was an open-label , nonr and omized , prospect i ve cohort study . HIV-1-infected pregnant women in Dar es Salaam were treated with zidovudine ( ZDV ) + lamivudine ( 3TC ) + nevirapine ( NVP ) . NVP was later replaced by nelfinavir for mothers with CD4 cell counts > 200 cells per microliter or with adverse reaction to NVP . HAART was initiated at 34 weeks of gestation . For women with symptomatic HIV infection or CD4 cell counts below 200 cells per microliter , HAART was started earlier if possible . Treatment of the mothers was stopped at 6 months except for those mothers who needed HAART for their own health . The infants received ZDV + 3TC for 1 week after birth . Mothers were advised to exclusively breastfeed and to wean abruptly between 5 and 6 months . Transmission of HIV-1 was analyzed using the Kaplan-Meier survival technique . Cox regression was used for comparison with the breastfeeding population of the Petra trial arm A. Results : There were 441 infants included in the analysis of HIV-1 transmission . The cumulative transmission of HIV-1 was 4.1 % [ 95 % confidence interval ( CI ) : 2.2 to 6.0 ] at 6 weeks , 5.0 % ( 95 % CI : 2.9 to 7.1 ) at 6 months , and 6.0 % ( 95 % CI : 3.7 to 8.3 ) at 18 months after delivery . The cumulative risk of HIV transmission between 6 weeks and 6 months was 1.0 % and between 6 months and 18 months 1.1 % . The cumulative HIV infection or death rate was 8.6 % ( 95 % CI : 6.0 to 11.2 ) at 6 months and 13.6 % ( 95 % CI : 10.3 to 16.9 ) at 18 months after delivery . Viral load at enrollment and duration of HAART before delivery were significantly associated with transmission but CD4 cell count at enrollment was not . The median time of breastfeeding was 24 weeks . The transmission in the Mitra Plus study was about half of the transmission in the breastfeeding population in the Petra trial arm A at 6 months after delivery ( adjusted relative hazard = 0.49 , P < 0.001 ) . The combined outcome HIV infection or death was significantly lower in the Mitra Plus study than in the breastfeeding population in the Petra trial arm A at 18 months ( adjusted relative hazard = 0.61 , P = 0.007 ) . NVP-related mucocutaneous rash was demonstrated in 6.5 % of 429 NVP-exposed women . The incidence of NVP-related grade 3 or 4 hepatotoxicity was low ( 0.5 % ) . Conclusions : HAART given to HIV-infected mothers in late pregnancy and during breastfeeding result ed in a low postnatal HIV transmission similar to that previously demonstrated in the Mitra study in Dar es Salaam using infant prophylaxis with 3TC during breastfeeding . The extended maternal prophylaxis with HAART for prevention of mother-to-child transmission of HIV-1 for breastfeeding mothers who do not need HAART for their own health should be further evaluated and compared with the use of infant postnatal antiretroviral prophylaxis regarding safety and cost-effectiveness Background : Rates of retention in care of HIV-positive pregnant women in care programs in Nigeria remain generally poor with rates around 40 % reported for specific programs . Poor quality of services in health facilities and long waiting times are among the critical factors militating against retention of these women in care . The aim of the interventions in this study is to assess whether a continuous quality improvement intervention using a Breakthrough Series approach in local district hospitals and primary health care clinics will lead to improved retention of HIV-positive women and mothers . Methods / Design : A cluster r and omized controlled trial with 32 health facilities r and omized to receive a continuous quality improvement/Breakthrough Series intervention or not . The care protocol for HIV-infected pregnant women and mothers is the same in all sites . The quality improvement intervention started 4 months before enrollment of individual HIV-infected pregnant women and initially focused on reducing waiting times for women and also ensuring that antiretroviral drugs are dispensed on the same day as clinic attendance . The primary outcome measure is retention of HIV-positive mothers in care at 6 months postpartum . Discussion : Results of this trial will inform whether quality improvement interventions are an effective means of improving retention in prevention of mother-to-child transmission of HIV programs and will also guide where health system interventions should focus to improve the quality of care for HIV-positive women . This will benefit policymakers and program managers as they seek to improve retention rates in HIV care programs BACKGROUND We evaluated the efficacy of a maternal triple-drug antiretroviral regimen or infant nevirapine prophylaxis for 28 weeks during breast-feeding to reduce postnatal transmission of human immunodeficiency virus type 1 ( HIV-1 ) in Malawi . METHODS We r and omly assigned 2369 HIV-1-positive , breast-feeding mothers with a CD4 + lymphocyte count of at least 250 cells per cubic millimeter and their infants to receive a maternal antiretroviral regimen , infant nevirapine , or no extended postnatal antiretroviral regimen ( control group ) . All mothers and infants received perinatal prophylaxis with single-dose nevirapine and 1 week of zidovudine plus lamivudine . We used the Kaplan-Meier method to estimate the cumulative risk of HIV-1 transmission or death by 28 weeks among infants who were HIV-1-negative 2 weeks after birth . Rates were compared with the use of the log-rank test . RESULTS Among mother-infant pairs , 5.0 % of infants were HIV-1-positive at 2 weeks of life . The estimated risk of HIV-1 transmission between 2 and 28 weeks was higher in the control group ( 5.7 % ) than in either the maternal-regimen group ( 2.9 % , P=0.009 ) or the infant-regimen group ( 1.7 % , P<0.001 ) . The estimated risk of infant HIV-1 infection or death between 2 and 28 weeks was 7.0 % in the control group , 4.1 % in the maternal-regimen group ( P=0.02 ) , and 2.6 % in the infant-regimen group ( P<0.001 ) . The proportion of women with neutropenia was higher among those receiving the antiretroviral regimen ( 6.2 % ) than among those in either the nevirapine group ( 2.6 % ) or the control group ( 2.3 % ) . Among infants receiving nevirapine , 1.9 % had a hypersensitivity reaction . CONCLUSIONS The use of either a maternal antiretroviral regimen or infant nevirapine for 28 weeks was effective in reducing HIV-1 transmission during breast-feeding . ( Clinical Trials.gov number , NCT00164736 . Abstract : UNAIDS has set a goal of achieving the elimination of mother-to-child transmission ( eMTCT ) of HIV by 2015 and keeping HIV-positive ( HIV+ ) mothers alive . In pursuit of this goal , in 2011 , the Malawi Ministry of Health ( MoH ) adopted the Option B+ strategy , which entails lifelong antiretroviral treatment for all HIV+ mothers , irrespective of severity of HIV infection . Poor mother – child pair retention is one of the major challenges against achieving this goal . To improve retention of mother – infant pairs in the eMTCT continuum of care , the Promoting Retention among Infants and Mothers Effectively ( PRIME ) study is evaluating the effectiveness of 3 models of health care delivery namely , mother – infant pair clinics , which deliver integrated HIV and non-HIV services , mother – infant pair clinics plus electronic text message ( SMS ) reminders for mother – infant pairs who miss scheduled eMTCT follow-up clinics , and current st and ard of care . The primary outcome is “ the proportion of HIV+ mothers and /or HIV-exposed infants ( HEI ) retained in eMTCT care at 12 months postpartum and received recommended HIV and non-HIV services during preceding scheduled visits . ” This 3-arm cluster r and omized intervention study is being implemented in 30 primary health facilities ( 10 facilities per arm ) in Mangochi and Salima districts , Malawi . At each clinic , a total of 41 HIV+ mothers attending maternal and child health services are being recruited and followed up for 18 months postpartum . This article describes the study methodology and interventions , successes and challenges experienced during the first 12 months of study implementation and relevance of study results to Malawi and other countries adopting the Option B+ strategy Background Pregnant women living with HIV ( WLH ) face daily challenges maintaining their own and their babies ' health and mental health . St and ard Prevention of Maternal to Child Transmission ( PMTCT ) programs are not design ed to address these challenges . Methods / Design As part of a cluster r and omized controlled trial , WLH are invited to attend four antenatal and four postnatal small group sessions led by a peer WLH ( a Peer Mentor ) . The WLH and their babies are assessed during pregnancy and at one week , six months , and twelve months post-birth . Mobile phones are used to collect routine information , complete question naires and remain in contact with participants over time . Pregnant WLH ( N = 1200 ) are r and omly assigned by clinic ( N = 8 clinics ) to an intervention program , called Masihambisane ( n = 4 clinics , n = 600 WLH ) or a st and ard care PMTCT control condition ( n = 4 clinics ; n = 600 WLH ) . Discussion Data collection with cellular phones are innovative and effective in low-re source setting s. St and ard PMTCT programs are not design ed to address the daily challenges faced by WLH ; Peer Mentors may be useful in supporting WLH to cope with these challenges . Trial registration Clinical Trials.gov registration # Background : Nigeria is a key target country in the global effort toward elimination of mother-to-child transmission of HIV . Low coverage of prevention of mother-to-child transmission ( PMTCT ) interventions , adherence , and retention-in-care rates in HIV-positive pregnant women are contributing factors to high mother-to-child transmission of HIV ( MTCT ) rates . In Nigeria , rural areas , served largely by primary health care facilities , have particularly poor indicators of PMTCT coverage . Mentor Mothers are HIV-positive women who serve as peer counselors for PMTCT clients , provide guidance , and support in keeping appointments and promoting antiretroviral adherence and retention-in-care . The Mother Mentor ( MoMent ) study aims to investigate the impact of structured Mentor Mother programs on PMTCT outcomes in rural Nigeria . Design and Methods : A prospect i ve cohort study will compare rates of retention-in-care among PMTCT clients who are supported by formally-trained supervised Mentor Mothers versus clients who receive st and ard-of-care , informal peer support . Study sites are 20 primary health care centers ( 10 intervention , 10 control ) in rural North- Central Nigeria . The study population is HIV-positive mothers and exposed infant pairs ( MIPs ) ( N = 480 ; 240 MIPs per study arm ) . Primary outcome measures are the proportion of exposed infants receiving early HIV testing by age 2 months , and the proportion of MIPs retained in care at 6 months postpartum . Secondary outcome measures examine antiretroviral adherence , 12-month postpartum MIP retention , and MTCT rates . This article presents details of the study design , the structured Mentor Mother programs , and how their impact on PMTCT outcomes will be assessed Background In rural South Africa , only two-thirds of HIV-positive pregnant women seeking antenatal care at community health centers took full advantage of ‘ prevention of mother-to-child transmission ’ ( PMTCT ) services in 2010 . Studies generally support male involvement to promote PMTCT , but the nature and impact of that involvement is unclear and untested . Additionally , stigma , disclosure and intimate partner violence pose significant barriers to PMTCT uptake and retention in care , suggesting that male involvement may be ‘ necessary , but not sufficient ’ to reduce infant HIV incidence . This study exp and s on a successful United States President 's Emergency Plan for AIDS Relief (PEPFAR)-supported PMTCT couples intervention pilot study conducted in the Mpumalanga province , targeting HIV-positive pregnant women and their partners , the primary objective being to determine whether male partner involvement plus a behavioral intervention will significantly reduce infant HIV incidence . Methods / design The study follows a cluster r and omized controlled design enrolling two cohorts of HIV-positive pregnant women recruited from 12 r and omly assigned Community Health Centers ( CHC ) ( six experimental , six control ) . The two cohorts will consist of women attending without their male partners ( n = 720 ) and women attending with their male partners ( n = 720 couples ) , in order to determine whether the influence of male participation itself , or combined with a behavioral PMTCT intervention , can significantly reduce infant HIV infection ante- , peri- and postnatally . Discussion It is our intention to significantly increase PMTCT participation from current levels ( 69 % ) in the Mpumalanga province to between 90 and 95 % through engaging women and couples in a controlled , six session ante- and postnatal risk-reducing and PMTCT promotion intervention addressing barriers to PMTCT ( such as stigma , disclosure , intimate partner violence , communication , infant feeding practice s and safer conception ) that prevent women and men from utilizing treatment opportunities available to them and their infants . Based upon the encouraging preliminary results from our pilot study , successful CHC adoption of the program could have major public health policy implication s for containing the epidemic among the most vulnerable population s in rural South Africa : HIV-positive pregnant women and their infants . Trial registration Clinical Trials.gov NCT02085356 ( registration date : 10 March 2014 ) Abstract : Prevention of mother-to-child transmission ( PMTCT ) elimination goals are hampered by low rates of retention and antiretroviral treatment adherence . The Eliminating Pediatric AIDS in Zimbabwe ( EPAZ ) project is assessing whether mother support groups ( MSGs ) increase rates of retention-in-care of HIV-positive mothers and their exposed infants , increase male participation , and improve other maternal and infant health outcomes . EPAZ is a cluster r and omized study involving 30 rural facilities in 2 health districts in Mutare province in eastern Zimbabwe . Facilities were r and omly assigned to either the st and ard-of-care or intervention arms . We established MSGs for HIV-positive mothers at the 15 health facilities in the intervention arm . MSGs met every 2 weeks and were led by an HIV-positive mother who was appointed as MSG coordinator ( MSG-C ) . MSG-Cs contacted nonattending patient-members of support groups by cell phone . If members still do not attend , MSG-Cs inform a health worker who initiates further outreach actions that are st and ard within the health system . At least 10 HIV-positive mothers are enrolled per facility . Enrollment started in July 2014 . The primary outcome measure is retention-in-care of HIV-exposed infants at 12 months of age . Secondary outcome measures are : retention-in-care of HIV-positive mothers at 12 months postpartum , male participation , and other maternal and child health indicators . The study relies on routine health system data supplemented by additional data using tools created for the study . If shown to improve PMTCT retention outcomes , facility-based MSGs have the potential to be scaled up throughout the Zimbabwe National PMTCT program and could be considered in other country programs Abstract : Evidence for Elimination ( E4E ) is a collaborative project established in 2012 as part of the INSPIRE ( INtegrating and Scaling up PMTCT through Implementation REsearch ) initiative . E4E is a cluster-r and omized trial with 2 arms ; St and ard of care and “ POC Plus ” [ in which point-of-care ( POC ) CD4 devices and related counseling support are provided ] ; aim ed at improving retention-in-care of HIV-infected pregnant women and mothers . In November 2013 , Zimbabwe adopted Option B+ for HIV-positive pregnant women under which antiretroviral treatment eligibility is no longer based on CD4 count . However , Ministry of Health and Child Care guidelines still require baseline and 6-monthly CD4 testing for treatment monitoring , until viral load testing becomes widely available . Considering the current limited capacity for viral-load testing , the significant investments in CD4 testing already made and the historical reliance on CD4 by health care workers for determining eligibility for antiretroviral treatment , E4E seeks to compare the impact of the provision of POC CD4 technology and early knowledge of CD4 levels on retention-in-care at 12 months , with the current st and ard of routine , laboratory-based CD4 testing . The study also compares rates of initiation and time-to-initiation between the 2 arms and according to level of maternal CD4 count , the cost of retaining HIV-positive pregnant women in care and the acceptability and feasibility of POC CD4 in the context of Option B+ . Outcome measures are derived from routine health systems data . E4E will provide data on POC CD4 testing and retention-in-care associated with Option B+ and serve as an early learning platform to inform implementation of Option B+ in Zimbabwe The objective of this study was to assess the acceptability and feasibility of a cell phone based case manager intervention targeting HIV-infected pregnant women on highly-active antiretroviral therapy ( HAART ) . Pregnant women ≥36 weeks gestation attending antenatal care and receiving HAART through the Option B+ program at a primary care clinic in South Africa were enrolled into a prospect i ve pilot intervention to receive text messages and telephone calls from a case manager through 6 weeks postpartum . Acceptability and feasibility of the intervention were assessed along with infant HIV testing rates and 10-week and 12-month postpartum maternal retention in care . Retention outcomes were compared to women of similar eligibility receiving care prior to the intervention . Fifty women were enrolled into the pilot from May to July 2013 . Most ( 70 % ) were HAART-naive at time of conception and started HAART during antenatal care . During the intervention , the case manager sent 482 text messages and completed 202 telephone calls , for a median of 10 text messages and 4 calls/woman . Ninety-six percent completed the postpartum interview and 47/48 ( 98 % ) endorsed the utility of the intervention . Engagement in 10-week postpartum maternal HIV care was > 90 % in the pre-intervention ( n = 50 ) and intervention ( n = 50 ) periods ; by 12-months retention fell to 72 % and was the same across periods . More infants received HIV-testing by 10-weeks in the intervention period as compared to pre-intervention ( 90.0 vs. 63.3 % , p < 0.01 ) . Maternal support through a cell phone based case manager approach was highly acceptable among South African HIV infected women on HAART and feasible , warranting further assessment of effectiveness BACKGROUND UNICEF/WHO recommends that infants born to HIV-infected mothers who do not have access to acceptable , feasible , affordable , sustainable , and safe replacement feeding should be exclusively breastfed for at least 6 months . The aim of three trials in Ethiopia , India , and Ug and a was to assess whether daily nevirapine given to breastfed infants through 6 weeks of age can decrease HIV transmission via breastfeeding . METHODS HIV-infected women breastfeeding their infants were eligible for participation . Participants were r and omly assigned to receive either single-dose nevirapine ( nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborns after birth ) or 6 week extended-dose nevirapine ( nevirapine 200 mg to women in labour and nevirapine 2 mg/kg to newborn babies after birth plus nevirapine 5 mg daily from days 8 - 42 for the infant ) . The r and omisation sequences were generated by computer at a central data coordinating centre . The primary endpoint was HIV infection at 6 months of age in infants who were HIV PCR negative at birth . Analyses were by modified intention to treat , excluding infants with missing specimens and those with indeterminate or confirmed HIV infection at birth . These studies are registered with Clinical Trials.gov , numbers NCT00074399 , NCT00061321 , and NCT00639938 . FINDINGS 2024 liveborn infants r and omised in the study had at least one specimen tested before 6 months of age ( 1047 infants in the single-dose group and 977 infants in the extended-dose group ) . The modified intention-to-treat population included 986 infants in the single-dose group and 901 in the extended-dose group . At 6 months , 87 children in the single-dose group and 62 in the extended-dose group were infected with HIV ( relative risk 0.80 , 95 % CI 0.58 - 1.10 ; p=0.16 ) . At 6 weeks of age , 54 children in the single-dose group and 25 in the extended-dose group were HIV positive ( 0.54 , 0.34 - 0.85 ; p=0.009 ) . 393 infants in the single-dose group and 346 in the extended-dose group experienced grade 3 or 4 serious adverse events during the study ( p=0.54 ) . INTERPRETATION Although a 6-week regimen of daily nevirapine might be associated with a reduction in the risk of HIV transmission at 6 weeks of age , the lack of a significant reduction in the primary endpoint-risk of HIV transmission at 6 months-suggests that a longer course of daily infant nevirapine to prevent HIV transmission via breast milk might be more effective where access to affordable and safe replacement feeding is not yet available and where the risks of replacement feeding are high . FUNDING US National Institutes of Health ; US National Institute of Allergy and Infectious Diseases ; Fogarty International Center Objective : To investigate the possibility of reducing mother-to-child transmission ( MTCT ) of HIV-1 through breast-feeding by prophylactic antiretroviral ( ARV ) treatment of the infant during the breast-feeding period . Design : An open-label , nonr and omized , prospect i ve cohort study in Tanzania ( Mitra ) . Methods : HIV-1-infected pregnant women were treated according to regimen A of the Petra trial with zidovudine ( ZDV ) and lamivudine ( 3TC ) from week 36 to 1 week postpartum . Infants were treated with ZDV and 3TC from birth to 1 week of age ( Petra arm A ) and then with 3TC alone during breast-feeding ( maximum of 6 months ) . Counseling emphasized exclusive breast-feeding . HIV transmission was analyzed using the Kaplan-Meier survival technique . Cox regression was used for comparison with the breast-feeding population in arm A of the Petra trial , taking CD4 cell count and other possible confounders into consideration . Results : There were 398 infants included in the transmission analysis in the Mitra study . The estimated cumulative proportion of HIV-1-infected infants was 3.8 % ( 95 % confidence interval [ CI ] : 2.0 to 5.6 ) at week 6 after delivery and 4.9 % ( 95 % CI : 2.7 to 7.1 ) at month 6 . The median time of breast-feeding was 18 weeks . High viral load and a low CD4 T-cell count at enrollment were associated with transmission . The Kaplan-Meier estimated risk of HIV-1 infection at 6 months in infants who were HIV-negative at 6 weeks was 1.2 % ( 95 % CI : 0.0 to 2.4 ) . The cumulative HIV-1 infection or death rate at 6 months was 8.5 % ( 95 % CI : 5.7 to 11.4 ) . No serious adverse events related to the ARV treatment of infants occurred . The HIV-1 transmission rate during breast-feeding in the Mitra study up to 6 months after delivery was more than 50 % lower than in the breast-feeding population of Petra arm A ( relative hazard = 2.61 ; P = 0.001 ; adjusted values ) . The difference in transmission up to 6 months was significant also in the sub population of mothers with CD4 counts ≥200 cells/μL. Conclusions : The rates of MTCT of HIV-1 in the Mitra study at 6 weeks and 6 months after delivery are among the lowest reported in a breast-feeding population in sub-Saharan Africa . Prophylactic 3TC treatment of infants to prevent MTCT of HIV during breast-feeding was well tolerated by the infants and could be a useful strategy to prevent breast milk transmission of HIV when mothers do not need ARV treatment for their own health Objective : To assess the noninferiority of a task-shifting HIV treatment model relying on peer counselors and nurses compared with a physician-centered model among HIV-1-positive women initiated on antiretroviral therapy ( ART ) at a prevention of mother-to-child transmission clinic in Mulago Hospital , Ug and a. Methods : HIV-1-infected ART eligible naive women were r and omized to either nurse – peer ( intervention ) or doctor – counselor ( st and ard model ) arm . The primary endpoint was virologic success defined attaining a viral load < 400 RNA copies per milliliter 6–12 months after ART initiation . Noninferiority was defined as the lower 95 % confidence limit for the difference in proportions with virologic success being less than 10 % . Secondary outcomes included immunologic success ( mean CD4 count increase from baseline ) and pill count . Results : Data on 85 participants were analyzed ( n = 45 in the intervention and n = 40 in the st and ard model ) . The proportion of participants with virologic success was similar in the st and ard and intervention models [ 91 % versus 88 % respectively ; difference , 3 % ; 95 % confidence interval ( CI ) : −11 % to 12 % ] . Probability of viral detection at 6–12 months ’ time point was similar in the 2 models ( log-rank test P = 0.73 ) . Immunologic and pill count indicators were also similar in the intervention and st and ard models , with mean CD4 increase of 217 versus 206 cells per microliter ( difference , 11 ; 95 % CI : −60 to 82 cells/&mgr;L ) and pill counts of 99.8 % versus 99.7 % ( difference , 0.0 ; 95 % CI : −5 % to 5 % ) respectively . Conclusions : Nurses and peer counselors were not inferior in providing ART follow-up care to postpartum women , an approach that may help deliver treatment to many more HIV-infected people BACKGROUND Novel strategies are needed to increase retention in and uptake of prevention of mother-to-child HIV transmission ( PMTCT ) services in sub-Saharan Africa . We aim ed to determine whether small , increasing cash payments , which were conditional on attendance at scheduled clinic visits and receipt of proposed services can increase the proportions of HIV-infected pregnant women who accept available PMTCT services and remain in care . METHODS In this r and omised controlled trial , we recruited newly diagnosed HIV-infected women , who were 32 or less weeks pregnant , from 89 antenatal care clinics in Kinshasa , Democratic Republic of Congo , and r and omly assigned ( 1:1 ) them to either the intervention group or the control group using computer-based r and omisation with varying block sizes of four , six , and eight . The intervention group received compensation on the condition that they attended scheduled clinic visits and accepted offered PMTCT services ( US$ 5 , plus US$ 1 increment at every subsequent visit ) , whereas the control group received usual care . Outcomes assessed included retention in care at 6 weeks ' post partum and uptake of PMTCT services , measured by attendance of all scheduled clinic visits and acceptance of proposed services up to 6 weeks ' post partum . Analyses were by intention to treat . This trial is registered with Clinical Trials.org , number NCT01838005 . FINDINGS Between April 18 , 2013 , and Aug 30 , 2014 , 612 potential participants were identified , 545 were screened , and 433 were enrolled and r and omly assigned ; 217 to the control group and 216 to the intervention group . At 6 weeks ' post partum , 174 participants in the intervention group ( 81 % ) and 157 in the control group ( 72 % ) were retained in care ( risk ratio [ RR ] 1·11 ; 95 % CI 1·00 - 1·24 ) . 146 participants in the intervention group ( 68 % ) and 116 in the control group ( 54 % ) attended all clinic visits and accepted proposed services ( RR 1·26 ; 95 % CI 1·08 - 1·48 ) . Results were similar after adjustment for marital status , age , and education . INTERPRETATION Among women with newly diagnosed HIV , small , incremental cash incentives result ed in increased retention along the PMTCT cascade and uptake of available services . The cost-effectiveness of these incentives and their effect on HIV-free survival warrant further investigation . FUNDING President 's Emergency Plan for AIDS Relief and the National Institute of Health and Child Development Objective : Many sub-Saharan African countries report high postpartum loss to follow-up of mother – baby pairs . We aim ed to determine whether interactive text messages improved rates of clinic attendance and early infant HIV testing in the Nyanza region of Kenya . Design : Parallel-group , unblinded , r and omized controlled trial . Methods : HIV-positive pregnant women at least 18 years old and enrolled in the prevention of mother-to-child transmission of HIV programme were r and omized to receive either text messages ( SMS group , n = 195 ) or usual care ( n = 193 ) . Messages were developed using formative focus group research informed by constructs of the Health Belief Model . The SMS group received up to eight text messages before delivery ( depending on gestational age ) , and six messages postpartum . Primary outcomes included maternal postpartum clinic attendance and virological infant HIV testing by 8 weeks postpartum . The primary analyses were intention-to-treat . Results : Of the 388 enrolled women , 381 ( 98.2 % ) had final outcome information . In the SMS group , 38 of 194 ( 19.6 % ) women attended a maternal postpartum clinic compared to 22 of 187 ( 11.8 % ) in the control group ( relative risk 1.66 , 95 % confidence interval 1.02–2.70 ) . HIV testing within 8 weeks was performed in 172 of 187 ( 92.0 % ) infants in the SMS group compared to 154 of 181 ( 85.1 % ) in the control group ( relative risk 1.08 , 95 % confidence interval 1.00–1.16 ) . Conclusions : Text messaging significantly improved maternal postpartum visit attendance , but overall return rates for these visits remained low . In contrast , high rates of early infant HIV testing were achieved in both arms , with significantly higher testing rates in the SMS compared to the control infants Abstract : In July 2011 , Malawi introduced an ambitious public health program known as “ Option B+ , ” which provides all HIV-infected pregnant and breastfeeding women with lifelong combination antiretroviral therapy , regardless of clinical stage or CD4 count . Option B+ is expected to have benefits for HIV-infected women , their HIV-exposed infants , and their HIV-uninfected male sex partners . However , these benefits hinge on early uptake of prevention of mother-to-child transmission , good adherence , and long-term retention in care . The Prevention of mother-to-child transmission Uptake and REtention ( PURE ) study is a 3-arm cluster r and omized controlled trial to evaluate whether clinic- or community-based peer support will improve care-seeking and retention in care by HIV-infected pregnant and breastfeeding women , their HIV-exposed infants , and their male sex partners , and ultimately improve health outcomes in all 3 population s. We describe the PURE Malawi Consortium , the initial work conducted to inform the trial and interventions , the trial design , and the analysis plan . We then discuss concerns and expected contributions to Malawi and the region BACKGROUND Effective strategies are urgently needed to reduce mother-to-child transmission of human immunodeficiency virus type 1 ( HIV-1 ) through breast-feeding in re source -limited setting s. METHODS Women with HIV-1 infection who were breast-feeding infants were enrolled in a r and omized , phase 3 trial in Blantyre , Malawi . At birth , the infants were r and omly assigned to one of three regimens : single-dose nevirapine plus 1 week of zidovudine ( control regimen ) or the control regimen plus daily extended prophylaxis either with nevirapine ( extended nevirapine ) or with nevirapine plus zidovudine ( extended dual prophylaxis ) until the age of 14 weeks . Using Kaplan-Meier analyses , we assessed the risk of HIV-1 infection among infants who were HIV-1-negative on DNA polymerase-chain-reaction assay at birth . RESULTS Among 3016 infants in the study , the control group had consistently higher rates of HIV-1 infection from the age of 6 weeks through 18 months . At 9 months , the estimated rate of HIV-1 infection ( the primary end point ) was 10.6 % in the control group , as compared with 5.2 % in the extended-nevirapine group ( P<0.001 ) and 6.4 % in the extended-dual-prophylaxis group ( P=0.002 ) . There were no significant differences between the two extended-prophylaxis groups . The frequency of breast-feeding did not differ significantly among the study groups . Infants receiving extended dual prophylaxis had a significant increase in the number of adverse events ( primarily neutropenia ) that were deemed to be possibly related to a study drug . CONCLUSIONS Extended prophylaxis with nevirapine or with nevirapine and zidovudine for the first 14 weeks of life significantly reduced postnatal HIV-1 infection in 9-month-old infants . ( Clinical Trials.gov number , NCT00115648 . Nigeria has more HIV-infected women who do not receive needed services for the prevention of mother-to-child transmission of HIV ( PMTCT ) than any other nation in the world . To meet the UNAIDS/WHO goal of eliminating mother-to-child HIV transmission by 2015 , multiple interventions will be required to scale up PMTCT services , especially to lower-level , rural health facilities . To address this , we are conducting a cluster-r and omized controlled study to evaluate the impact and cost-effectiveness of a novel , family-focused integrated package of PMTCT services . A systematic re-assignment of patient care responsibilities coupled with the adoption of point-of-care CD4 + cell count testing could facilitate the ability of lower-cadre health providers to manage PMTCT care , including the provision and scale-up of antiretroviral therapy ( ART ) to pregnant women in rural setting s. Additionally , as influential community members , male partners could support their partners ' uptake of and adherence to PMTCT care . We describe an innovative approach to scaling up PMTCT service provision that incorporates considerations of where and from whom women can access services ( task-shifting ) , ease of obtaining a CD4 + cell count result ( point-of-care testing ) , the degree of HIV service integration for HIV-infected women and their infants , and the level of family and community involvement ( specifically male partner involvement ) . This systematic approach , if proven feasible and effective , could be scaled up in Nigeria and similar re source -limited setting s as a means to accelerate progress toward eliminating mother-to-child transmission of HIV and help women with HIV infection take ART and live long , healthy lives ( Trial registration : NCT01805752 ) Background : Integrating antenatal care ( ANC ) and HIV care may improve uptake and retention in services along the prevention of mother-to-child transmission ( PMTCT ) cascade . This study aim ed to determine whether integration of HIV services into ANC setting s improves PMTCT service utilization outcomes . Methods : ANC clinics in rural Kenya were r and omized to integrated ( 6 clinics , 569 women ) or nonintegrated ( 6 clinics , 603 women ) services . Intervention clinics provided all HIV services , including highly active antiretroviral therapy ( HAART ) , whereas control clinics provided PMTCT services but referred women to HIV care clinics within the same facility . PMTCT utilization outcomes among HIV-infected women ( maternal HIV care enrollment , HAART initiation , and 3-month infant HIV testing uptake ) were compared using generalized estimating equations and Cox regression . Results : HIV care enrollment was higher in intervention compared with control clinics [ 69 % versus 36 % ; odds ratio = 3.94 , 95 % confidence interval ( CI ) : 1.14 to 13.63 ] . Median time to enrollment was significantly shorter among intervention arm women ( 0 versus 8 days , hazard ratio = 2.20 , 95 % CI : 1.62 to 3.01 ) . Eligible women in the intervention arm were more likely to initiate HAART ( 40 % versus 17 % ; odds ratio = 3.22 , 95 % CI : 1.81 to 5.72 ) . Infant testing was more common in the intervention arm ( 25 % versus 18 % ) , however , not statistically different . No significant differences were detected in postnatal service uptake or maternal retention . Conclusions : Service integration increased maternal HIV care enrollment and HAART uptake . However , PMTCT utilization outcomes were still suboptimal , and postnatal service utilization remained poor in both study arms . Further improvements in the PMTCT cascade will require additional research and interventions Cost-Benefit of ART In the battle to control HIV , mass antiretroviral treatment ( ART ) costs $ 500 to $ 900 per person per year . Bor et al. ( p. 961 ) calculated the impact of intensifying ART on the life expectancy of people living in rural KwaZulu Natal . The date s of death were collected from a population of about 100,000 people during 2000–2011 : Four years before and 8 years after the scaling up of ART . Life expectancy of adults increased by more than 11 years after ART was exp and ed , and the economic value of the lifetimes gained were calculated to far exceed the cost of treatment . Tanser et al. ( p. 966 ) followed nearly 17,000 HIV-uninfected individuals in KwaZulu-Natal over an 8-year period . Holding other HIV risk factors constant , individual HIV acquisition risk declined significantly with increasing ART coverage of HIV-infected people . The risk of acquiring HIV is reduced in rural communities via large-scale delivery of antiretroviral therapy . The l and mark HIV Prevention Trials Network ( HPTN ) 052 trial in HIV-discordant couples demonstrated unequivocally that treatment with antiretroviral therapy ( ART ) substantially lowers the probability of HIV transmission to the HIV-uninfected partner . However , it has been vigorously debated whether substantial population -level reductions in the rate of new HIV infections could be achieved in " real-world " sub-Saharan African setting s where stable , cohabiting couples are often not the norm and where considerable operational challenges exist to the successful and sustainable delivery of treatment and care to large numbers of patients . We used data from one of Africa 's largest population -based prospect i ve cohort studies ( in rural KwaZulu-Natal , South Africa ) to follow up a total of 16,667 individuals who were HIV-uninfected at baseline , observing individual HIV seroconversions over the period 2004 to 2011 . Holding other key HIV risk factors constant , individual HIV acquisition risk declined significantly with increasing ART coverage in the surrounding local community . For example , an HIV-uninfected individual living in a community with high ART coverage ( 30 to 40 % of all HIV-infected individuals on ART ) was 38 % less likely to acquire HIV than someone living in a community where ART coverage was low ( < 10 % of all HIV-infected individuals on ART ) |
12,880 | 19,862,586 | Conclusions These results suggest patients undergoing TJA are less active than recommended to achieve health-enhancing activity levels ( greater than 10,000 steps/day ) , but they appear more active than normally assumed in typical wear simulations . | Background Qualitative research studies regarding physical activity in patients undergoing total joint arthroplasty ( TJA ) unfortunately are sparse in the current literature .
Questions / Purpose sTo provide a foundation for future investigations , we performed a systematic review to identify the different instruments used to quantify physical activity in patients undergoing TJA and to determine how active these patients really are . | OBJECTIVE To determine if physical activity was a risk factor for revision arthroplasty after primary total knee arthroplasty ( TKA ) due to osteoarthritis ( OA ) within the previous 15 years . METHODS This was a matched case-control study . The cases had primary TKA followed by revision arthroplasty . Controls had primary TKA and no revision arthroplasty . Cases and controls were matched for age , sex , number of knees replaced , and date of primary TKA . St and ardized telephone interviews were conducted to assess historical leisure activity , occupational activity , and instrumental activities of daily living after primary TKA in metabolic equivalent (MET)-hours per week . Conditional logistic regression was performed to identify the variables that predicted the need for revision arthroplasty . RESULTS Seventeen female and 9 male pairs , aged 47 to 85 years , participated . Most of the reported activity was of low impact and low or moderate intensity . Cases reported a median of 44.5 ( range 0 to 137 ) MET-hours of total historical physical activity per week compared with controls ' 55.1 ( range 0 to 278 ) MET-hours . Total historical physical activity was not associated with the risk of revision arthroplasty ( OR 0.99 , 95 % CI 0.99 - 1.01 ) . Participants with primary TKA ( controls ) consistently reported more MET-hours of leisure and occupational activity than those with revision arthroplasty ( cases ) regardless of the number of knees replaced or whether or not walking was accounted for . CONCLUSION This study quantified and described patterns of physical activity in a population with TKA . Physical activity did not appear to be a risk factor for revision arthroplasty . Our results suggest that individuals undergoing primary TKA should be encouraged to remain active after surgery BACKGROUND Until now , the activity of the lower limb could only be exactly measured with expensive electronic pedometers . The aim of this study was to develop a feasible question naire to measure the activity of patients after arthroplasty . METHODS The " Daily Activity Question naire " ( DAQ ) was developed in several steps and the evaluation was carried out in three groups of patients with osteoarthritis of the hip ( 160 patients and 855 investigated days ) . The psychometric characteristics were verified . RESULTS The retest reliability ( ICC ) of the DAQ is in a range comparable to the electronic pedometer StepWatch . The testing of the criterion validity showed high correlations between the StepWatch and the DAQ ( r=0.743 ) . CONCLUSION Because of its high correlations to the load changes actually performed , the DAQ is especially suited to answer arthroplasty-related questions . In all patient groups , projected load changes between 1.8 and 2.4 million per year were found , which by far exceed the generally accepted test st and ards for endoprostheses CONTEXT Recent guidelines for treatment of overweight and obesity include recommendations for risk stratification by disease conditions and cardiovascular disease ( CVD ) risk factors , but the role of physical inactivity is not prominent in these recommendations . OBJECTIVE To quantify the influence of low cardiorespiratory fitness , an objective marker of physical inactivity , on CVD and all-cause mortality in normal-weight , overweight , and obese men and compare low fitness with other mortality predictors . DESIGN Prospect i ve observational data from the Aerobics Center Longitudinal Study . SETTING Preventive medicine clinic in Dallas , Tex . PARTICIPANTS A total of 25714 adult men ( average age , 43.8 years [ SD , 10.1 years ] ) who received a medical examination during 1970 to 1993 , with mortality follow-up to December 31 , 1994 . MAIN OUTCOME MEASURES Cardiovascular disease and all-cause mortality based on mortality predictors ( baseline CVD , type 2 diabetes mellitus , high serum cholesterol level , hypertension , current cigarette smoking , and low cardiorespiratory fitness ) stratified by body mass index . RESULTS During the study period , there were 1025 deaths ( 439 due to CVD ) during 258781 man-years of follow-up . Overweight and obese men with baseline CVD or CVD risk factors were at higher risk for all-cause and CVD mortality compared with normal-weight men without these predictors . Using normal-weight men without CVD as the referent , the strongest predictor of CVD death in obese men was baseline CVD ( age- and examination year-adjusted relative risk [ RR ] , 14.0 ; 95 % confidence interval [ CI ] , 9.4 - 20.8 ) ; RRs for obese men with diabetes mellitus , high cholesterol , hypertension , smoking , and low fitness were similar and ranged from 4.4 ( 95 % CI , 2.7 - 7.1 ) for smoking to 5.0 ( 95 % CI , 3.6 - 7.0 ) for low fitness . Relative risks for all-cause mortality in obese men ranged from 2.3 ( 95 % CI , 1.7 - 2.9 ) for men with hypertension to 4.7 ( 95 % CI , 3.6 - 6.1 ) for those with CVD at baseline . Relative risk for all-cause mortality in obese men with low fitness was 3.1 ( 95 % CI , 2.5 - 3.8 ) and in obese men with diabetes mellitus 3.1 ( 95 % CI , 2.3 - 4.2 ) and as slightly higher than the RRs for obese men who smoked or had high cholesterol levels . Low fitness was an independent predictor of mortality in all body mass index groups after adjustment for other mortality predictors . Approximately 50 % ( n = 1674 ) of obese men had low fitness , which led to a population -attributable risk of 39 % for CVD mortality and 44 % for all-cause mortality . Baseline CVD had population attributable risks of 51 % and 27 % for CVD and all-cause mortality , respectively . CONCLUSIONS In this analysis , low cardiorespiratory fitness was a strong and independent predictor of CVD and all-cause mortality and of comparable importance with that of diabetes mellitus and other CVD risk factors Introduction The health benefits of regular cardiovascular exercise are well-known . Such exercise , however , has traditionally been defined as vigorous physical activity , such as jogging , swimming , or aerobic dance . Exercise of moderate intensity also promotes health , and many U.S. adults may be experiencing the health benefits of exercise through lifestyle activities of moderate intensity , such as yard work , housework , or walking for transportation . Until recently , public health surveillance systems have not included assessment s of this type of physical activity , focusing on exercise of vigorous intensity . We used an enhanced surveillance tool to describe the prevalence and amount of both moderate-intensity and vigorous-intensity physical activity among U.S. adults . Methods We analyzed data from the 2001 Behavioral Risk Factor Surveillance System , a state-based , r and om-digit – dialed telephone survey administered to U.S. adults aged 18 years and older ( n = 82,834 men and 120,286 women ) . Physical activity behavior was assessed using questions design ed to quantify the frequency of participation in moderate- or vigorous-intensity physical activities performed during leisure time or for household chores and transportation . Results Overall , 45 % of adults ( 48 % of men and 43 % of women ) were active at recommended levels during nonworking hours ( at least 30 minutes five or more days per week in moderate-intensity activities , equivalent to brisk walking , or at least 20 minutes three or more days per week in vigorous activities , equivalent to running , heavy yard work , or aerobic dance ) . Less than 16 % of adults ( 15 % of men and 17 % of women ) reported no moderate or vigorous activity in a usual week . Conclusion Integrating surveillance of lifestyle activities into national systems is possible , and doing so may provide a more accurate representation of the prevalence of recommended levels of physical activity . These results , however , suggest that the majority of U.S. adults are not active at levels associated with the promotion and maintenance of health Abstract Limitation in daily physical activity is one of the reasons for total hip arthroplasty ( THA ) or total knee arthroplasty ( TKA ) . However , studies of the effects of THA or TKA generally do not determine actual daily activity as part of physical functioning . We determined the effect of THA or TKA on patients ’ actual physical activity and body function ( pain , stiffness ) , capacity to perform tasks , and self-reported physical functioning . We also assessed whether there are differences in the effect of the surgery between patients undergoing THA or TKA and whether the improvements vary between these different outcome measures . We recruited patients with long-st and ing end-stage osteoarthritis of the hip or knee awaiting THA or TKA . Measurements were performed before surgery and 3 and 6 months after surgery . Actual physical activity improved by 0.7 % . Patients ’ body function , capacity , and self-reported physical functioning also improved . The effects of the surgery on these aspects of physical functioning were similar for THA and TKA . The effect on actual physical activity ( 8 % ) was smaller than on body function ( 80%–167 % ) , capacity ( 19%–36 % ) , and self-reported physical functioning ( 87%–112 % ) . Therefore , in contrast to the large effect on pain and stiffness , patients ’ capacity , and their self-reported physical functioning , the improvement in actual physical activity of our patients was less than expected 6 months after surgery . Level of Evidence : Level I , prospect i ve study . See the Guidelines for Authors for a complete description of levels of evidence This study examined the effect of the surgical approach used in total hip arthroplasty ( THA ) on gait mechanics six months following surgery . Quantitative gait analysis was performed on 29 subjects : 10 anterolateral ( A-L ) and 10 posterolateral ( P-L ) THA patients and nine able-bodied , velocity-matched subjects . Discriminant function analysis was used to determine the distinction of the groups with respect to sagittal plane hip range of motion , index of symmetry , trunk inclination , pelvic drop , hip abduction , and foot progression angles . The A-L group had the largest trunk inclination ( 3.0+/-2.4 degrees ) and the smallest hip range of motion ( 34.0+/-7.4 degrees ) . Both THA groups demonstrated greater asymmetry as expressed by the smaller symmetry index ( 0.97+/-0.04 for A-L and 0.98+/-0.05 for the P-L ) than the able-bodied group ( 0.99+/-0.01 ) . The classification procedure correctly classified 89 % of the control group cases , 90 % of the A-L cases , and 50 % of the P-L cases . These results support the conclusion that six months following surgery , the gait of the majority ( 85 % ) of THA patients has not returned to normal . The A-L patients displayed distinct gait patterns , while a small percentage ( 30 % ) of the P-L patients demonstrated normal gait . While these differences are statistically significant , the clinical significance is unknown and linked to the duration that they persist Accumulating data suggest that the amount of use , and not simply the duration in situ , influences the wear and survival of total joint replacements . An electronic , digital pedometer was used to record the number of steps taken by 111 non-r and omized volunteers who had had at least one total hip or knee replacement . The patients averaged 4988 steps per day , which extrapolates to approximately 0.9 million cycles per year for each joint of the lower extremity . Average activity ranged widely from 395 to 17,718 steps per day , an approximately forty-five-fold difference . The most active patient walked more than 3.5 times the average number of steps per day . Age was significantly associated with activity ( p = 0.048 ) , but there was a high degree of variability ( st and ard deviation , 3040 steps per day ) . Patients who were less than sixty years old walked 30 per cent more on average than those who were sixty years old or more ( p = 0.023 ) . Men walked 28 per cent more on average than women ( p = 0.037 ) , and men who were less than sixty years old walked 40 per cent more on average than the rest of the patients ( p = 0.011 ) . These data indicate that individual differences in the activity of the patient can be a substantial source of variability in rates of polyethylene wear in vivo . The pedometer is an inexpensive investigational tool with many potential applications , including st and ardizing wear measurements of joint replacements on the basis of gait cycles rather than time . This quantitative approach may provide prognostic information regarding the survival of joint prostheses . Pedometer data may also be useful for quantitative assessment of walking ability in outcome studies BACKGROUND Wear of the acetabular cup and implant loosening in total hip arthroplasty are thought to be affected by individual patient activity levels . METHODS Activity levels of 100 patients with unilateral primary hip replacements were measured using a digital pedometer 10-years post-operatively . FINDINGS Activity rates of hip replacement patients 10 years post surgery were found to fall with increasing age strata , with the age group 70 - 74 years showing significantly reduced activity rates compared to the 55 - 64 years age group and the age group greater than 80 years showing significantly reduced activity rates compared to both the 55 - 64 years age group and the 65 - 69 years age group . However , a clear correlation between age and activity was not found . Acetabular cup wear showed no relationship with patient activity levels . INTERPRETATION Progressive reduction in activity levels with more elderly hip replacement patients may inform long term planning of hip arthroplasty and implant choice CONTEXT Low levels of cardiorespiratory fitness are associated with high risk of mortality , and improvements in fitness are associated with reduced mortality risk . However , a poor underst and ing of the physical activity-fitness dose response relation remains . OBJECTIVE To examine the effect of 50 % , 100 % , and 150 % of the NIH Consensus Development Panel recommended physical activity dose on fitness in women . DESIGN , SETTING , AND PARTICIPANTS R and omized controlled trial of 464 sedentary , postmenopausal overweight or obese women whose body mass index ranged from 25.0 to 43.0 and whose systolic blood pressure ranged from 120.0 to 159.9 mm Hg . Enrollment took place between April 2001 and June 2005 in the Dallas , Tex , area . INTERVENTION Participants were r and omly assigned to 1 of 4 groups : 102 to the nonexercise control group and 155 to the 4-kcal/kg , 104 to the 8-kcal/kg , and 103 to the 12-kcal/kg per week energy-expenditure groups for the 6-month intervention period . Target training intensity was the heart rate associated with 50 % of each woman 's peak Vo2 . MAIN OUTCOME MEASURE The primary outcome was aerobic fitness assessed on a cycle ergometer and quantified as peak absolute oxygen consumption ( Vo2abs , L/min ) . RESULTS The mean ( SD ) baseline Vo2abs values were 1.30 ( 0.25 ) L/min . The mean ( SD ) minutes of exercising per week were 72.2 ( 12.3 ) for the 4-kcal/kg , 135.8 ( 19.5 ) for the 8-kcal/kg , and 191.7 ( 33.7 ) for the 12-kcal/kg per week exercise groups . After adjustment for age , race/ethnicity , weight , and peak heart rate , the exercise groups increased their Vo2abs compared with the control group by 4.2 % in the 4-kcal/kg , 6.0 % in the 8-kcal/kg , and 8.2 % in the 12-kcal/kg per week groups ( P<.001 for each vs control ; P for trend < .001 ) . There was no treatment x subgroup interaction for age , body mass index , weight , baseline Vo2abs , race/ethnicity , or baseline hormone therapy use . There were no significant changes in systolic or diastolic blood pressure values from baseline to 6 months in any of the exercise groups vs the control group . CONCLUSION In this study , previously sedentary , overweight or obese postmenopausal women experienced a grade d dose-response change in fitness across levels of exercise training . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00011193 Exercise has become a st and ard therapy for patients with type 2 diabetes ( 1 ) . Regular exercise improves conventional clinical risk factors , cardiorespiratory fitness , and components of the insulin resistance syndrome ( 2 - 6 ) . However , it is unclear whether physical activity improves the prognosis of patients with diabetes . No data are available on the association of physical activity or cardiorespiratory fitness with mortality in patients with diabetes . The overall benefit of exercise for these patients is unclear , and some experts are concerned that macrovascular and microvascular complications may be worsened by an exercise program ( 1 , 7 ) . Some consider exercise only as a supplement to diet therapy ( 8) . Studies have shown repeatedly that low cardiorespiratory fitness and physical inactivity are directly associated with cardiovascular disease and all-cause mortality ( 9 - 14 ) , and our preliminary study with a small number of end points suggested that this association might persist across plasma glucose levels ( 15 ) . In the current study , we evaluated the prospect i ve association of cardiorespiratory fitness and physical inactivity with mortality in men who have type 2 diabetes . Methods The material presented in this report was derived from the Aerobics Center Longitudinal Study ( ACLS ) , a prospect i ve observational study of patients examined at The Cooper Clinic in Dallas , Texas . The study was review ed and approved annually by the institutional review board at The Cooper Institute . Additional details of study methods and study group characteristics of this cohort have been published elsewhere ( 12 , 13 ) . Patients Participants were men with type 2 diabetes who completed a baseline medical evaluation at The Cooper Clinic in Dallas , Texas , during 1970 to 1993 . These men came to The Cooper Clinic for a medical examination and health counseling . Many were sent by their employers for these services , some were referred by their personal physicians , and others were self-referred . More than 92 % of the patients are white , and most are employed in executive or professional occupations ; more than 75 % are college graduates . Study participants come from middle and upper socioeconomic strata , but they are similar to other well-characterized study group-based cohorts in terms of blood pressure , cholesterol level , body weight , and cardiorespiratory fitness ( 6 , 16 , 17 ) . We excluded men taking insulin and those with a history of cancer at baseline . Clinical Examination The baseline evaluation was performed after participants gave informed written consent for the baseline medical examination and registration in the follow-up study . Examinations followed an overnight fast of at least 12 hours and included personal and family health histories , a question naire on demographic characteristics and health habits , a physical examination , a maximal exercise test on a treadmill , anthropometry , electrocardiography , blood chemistry analyses , and blood pressure measurement . Technicians who followed a st and ard manual of operations administered all procedures . Question naire Patients completed an extensive self-report of personal and family medical diseases and conditions . Each clinic physician examines only four or five patients per day and thus has time for thorough additional probing of items on the self-reported question naire . This complete review of the patient 's medical history and the subsequent physical examination are strengths of the ACLS and provide a more thorough evaluation of baseline health status than is possible in many epidemiologic studies . The question naire also featured items on health habits , including current smoking status and smoking history and whether the participant was currently dieting to lose weight or following any other special dietary plan . Physical activity pattern was ascertained by self-report on the question naire . An extensive list of leisure-time physical activities was presented , and participants indicated activities in which they had participated in the 3 months before the examination . In later study years , they gave additional details on the number of times per week and the duration of exercise sessions . Laboratory Evaluations Cardiorespiratory fitness was assessed by using a maximal exercise test that followed a modified version of Balke and Ware 's protocol ( 18 ) . Briefly , the test began with the participant walking on a horizontal treadmill at 88 m/min . After the first minute , the elevation increased to 2 % , and it further increased 1 % each minute up to 25 minutes . For the few patients who were still able to continue , the elevation was held constant after 25 minutes and the speed increased to 5.4 m/min until the participant reached volitional fatigue . Exercise test performance with this protocol correlates highly with measured maximal oxygen uptake ( r=0.92 ) ( 19 ) . Serum sample s were analyzed by using automated techniques in a laboratory that participates in and meets the quality control st and ards of the Centers for Disease Control and Prevention Lipid St and ardization Program . Blood pressure was measured by auscultatory methods with a mercury sphygmomanometer according to American Heart Association guidelines ( 20 ) . The lowest of three blood pressure measurements at the clinic examination was recorded as the baseline blood pressure . Height and weight were measured by using a st and ard beam-balance scale and stadiometer , and body mass index was calculated . Type 2 Diabetes Diabetes was defined according to criteria of the American Diabetes Association : fasting plasma glucose level of 7.0 mmol/L or greater ( 126 mg/dL ) ( 21 ) . Three hundred seventy patients who did not meet this criterion but who gave a history of physician-diagnosed diabetes were considered to have diabetes . Patients were classified as having known diabetes or unknown diabetes according to their diabetes status before the baseline Cooper Clinic examination . Definition of Exposure Variables The principal exposure variables used in our analyses were cardiorespiratory fitness and self-reported physical activity . These exposures were determined at the baseline examination . Cardiorespiratory Fitness We categorized total time from the maximal exercise test into frequency distributions for specific age groups ( 30 to 39 , 40 to 49 , 50 to 59 , and 60 years ) . The least fit 20 % of the participants in each age group were classified as low fit , the next 40 % of the distribution as moderately fit , and the highest 40 % as high fit . We have used these cut-points to define fitness in previous studies ( 12 , 13 ) , and they are based on our entire cohort rather than on diabetic patients only . We selected these cut-points before undertaking the current analysis . Cardiorespiratory fitness is expressed as maximal metabolic units ( METs ) attained during the exercise test . The METs are calculated as the working metabolic rate divided by the resting metabolic rate , and 1 MET is equivalent to an oxygen uptake of 3.5 mL1 kg 1 . Physical Activity Patients who reported walking , jogging , or participating in aerobic exercise programs in the 3 months before the examination were classified as active , regardless of the frequency and duration of exercise . Otherwise , patients were classified as inactive . In our cohort , more than 76 % of men who reported being active at baseline still reported being active at the second visit after more than 1 year . In comparison , only 34 % of men who reported being inactive at baseline reported being active at the second examination ( P<0.001 ) . Self-reported physical activity status in our cohort is correlated with maximal exercise test performance ( 6 , 22 ) . Baseline or Parental Cardiovascular Disease We defined baseline cardiovascular disease as a personal history of heart attack , stroke , or a revascularization procedure ; an abnormal resting or exercise electrocardiogram ; or the highest heart rate during exercise testing that was less than 85 % of the age-predicted maximal heart rate ( [ 220 age in years ] 0.85 ) . Men who reported a history of cardiovascular disease in either parent were classified as having parental cardiovascular disease . Conventional Cardiovascular Disease Risk Factors We assigned men to risk strata for conventional cardiovascular disease risk factors on the basis of recent recommendations ( 23 ) . We defined high blood pressure as systolic blood pressure of 140 mm Hg or more , diastolic blood pressure of 90 mm Hg or more , or a history of physician-diagnosed hypertension . We classified participants with a total cholesterol level of 6.2 mmol/L ( 240 mg/dL ) or more as having high cholesterol , those with self-reported current smoking as current smokers , those with a self-reported parental history of myocardial infa rct ion or stroke as having a history of parental cardiovascular disease , those with a body mass index less than 25.0 kg/m2 as normal weight , and those with a body mass index of 25.0 kg/m2 or more as overweight . Statistical Analysis Our primary outcome measure was all-cause mortality . We used the National Death Index to identify decedents in the ACLS . The National Death Index has been shown to be an effective , accurate means of ascertaining deaths in the general population , with a sensitivity of about 96 % and a specificity of 100 % ( 24 ) . We obtained official death certificates from states in which there were ACLS decedents , and we had the certificates coded by a nosologist according to the International Classification of Diseases , Ninth Revision . Only the underlying cause of death was used in analyses for this report . Data were analyzed by using the SAS statistical package ( SAS Institute , Inc. , Cary , North Carolina ) . The analyses assumed that physical activity and fitness were essentially unchanged during the study period . We used survival curves to estimate survival function against time and log [ log ( survival time ) ] to check the proportional hazards model assumption . Log [ log ( survival function ) ] estimates were approximately parallel across exposure Quantitative assessment of patient activity is important in evaluating the outcomes of joint prostheses , and such methods are gaining popularity . The single greatest impediment to quantitative activity assessment is patient compliance . How many days of sampling are necessary to provide reliable and accurate estimates of walking activity ? The current study analyzes how well sampling for 4 consecutive days of activity compares to assessing activity for 7 or more days with the same pedometer in 131 patients with either a total hip or total knee prosthesis . The mean steps per day obtained throughout the full-length sampling ( 7 - 123 days ) was strongly correlated to the one obtained from the r and om consecutive 4-day sample ( r2 = 0.94 , P < .001 ) with only 5 outliers . The 4-day activity assessment gave an underestimation of 4.7 % ( P = .5 ) . The number of outliers increased with fewer days of sampling . Monitoring activity for 4 consecutive days yields a quantitative assessment that is within 5 % of a sampling of 7 or more days Purpose . This study was design ed ( 1 ) to examine the effects of a 10,000 steps·d−1 exercise prescription on sedentary , overweight/obese adults , and ( 2 ) to examine the effects of adherence on body composition and cardiovascular risk factors . Methods . Fifty-six overweight/obese adults participated in the study . Body composition and cardiovascular risk factors were determined at baseline , 20 weeks , and 36 weeks . Adherence was defined as averaging ≥ 9500 steps·d−1 from week 4 to week 36 . Results . 38 participants ( 68 % ) wore pedometers daily for 36 weeks and were available for posttesting . Significant improvements were noted in mean values for walking volume ( 3994 steps·d−1 ) , body weight ( –2.4 kg ) , body mass index ( –0.8 kg·m−2 ) , percentage body fat ( –1.9 % ) , fat mass ( –2.7 kg ) , waist circumference ( –1.8 cm ) , hip circumference ( –1.9 cm ) and high-density lipoprotein ( 3 mg/dl ) . The adherers had large improvements in body composition measures , whereas the nonadherers showed little or no change in these variables . Discussion . A 10,000 steps·d−1 exercise prescription result ed in weight loss over 36 weeks in previously sedentary , overweight/obese adults . Adherence to the step goal had a marked effect on the outcome |
12,881 | 26,951,143 | Conclusion : The results indicated that subthreshold r and om noise improves balance and sensation in diabetic patients and elder people .
Also gait variables can be improved in elder people with subthreshold r and om noise . | Background : Central nervous system receives information from foot mechanoreceptors in order to control balance and perform movement tasks .
Subthreshold r and om noise seems to improve sensitivity of the cutaneous mechanoreceptor .
Objectives : The purpose of this study was to systematic ally review published evidence conducted to evaluate the clinical and biomechanical effects of subthreshold r and om noise on the plantar surface of the foot in diabetic patients and elder people . | The aim of this study was to investigate the influence of reduced plantar sensation on gait patterns during walking in 20 healthy subjects ( 25.9 + /- years , 61.6 + /- 11.5 kg , 178 + /- 9.5 cm ) with no history of sensory disorders . Force plate measurements , electromyography ( EMG ) measurements and a three-dimensional movement analysis were performed simultaneously during barefoot walking before and after reduction of plantar sensation using an ice immersion technique . The results show that reduced plantar sensation leads to significant changes in gait patterns that are present at the ankle , knee and hip joint and indicate a more cautious ground contact and push-off with modified EMG and motion patterns Pressures under the foot during level walking were measured in 15 healthy young adults ( 8 females , 7 males , mean age 25.7 , S.D. 5.3 ) before and after immersing the feet in ice-cold water ( 2 degrees C ) for 30 min to evaluate the role of plantar insensitivity on gait patterns . Following ice water immersion , there was a significant decrease in walking speed . Maximum forces and peak pressures under the foot decreased , with the exception of an increase in loading under the third to fifth metatarsal heads . Contact times increased under all regions of the foot , and force-time and pressure-time integrals increased under the second and third to fifth metatarsal head regions . It is concluded that plantar insensitivity significantly alters the distribution , duration , and to a lesser extent , the magnitude of forces and pressures under the foot when walking . These results suggest that in the neuropathic foot , gait changes caused by plantar insensitivity may be partly responsible for the redistribution and altered duration of loading , whereas the increase in the magnitude of forces and pressures are primarily due to other disease-related factors OBJECTIVE To test the hypothesis that vibrotactile detection thresholds in older adults , patients with stroke , and patients with diabetic neuropathy can be significantly reduced with the introduction of mechanical noise . DESIGN A r and omized controlled study . SETTING A university research laboratory . PARTICIPANTS Twelve healthy elderly subjects ( age range , 67 - 85y ) , 5 patients with stroke ( age range , 24 - 64y ) , and 8 patients with diabetic neuropathy ( age range , 53 - 77y ) . INTERVENTIONS Each subject 's detection thresholds ( ie , minimum level of stimulus to be detected ) for a vibrotactile stimulus without and with mechanical noise ( ie , r and om vibration with a small intensity ) were determined by using a 4- , 2- , and 1-stepping algorithm . The stimuli were applied to the fingertip and /or to the first metatarsal of the foot . MAIN OUTCOME MEASURE Detection threshold for a vibrotactile stimulus . RESULTS The detection threshold at the fingertip for the vibration stimulus with mechanical noise was significantly lower than that without mechanical noise for all 12 elderly subjects , for 4 of the 5 patients with stroke , and all 8 patients with diabetic neuropathy . For the 8 patients with diabetes , mechanical noise also significantly reduced the vibrotactile detection threshold at the foot . CONCLUSIONS Reduced vibrotactile sensitivity in older adults , patients with stroke , and patients with diabetic neuropathy can be significantly improved with input mechanical noise . Noise-based techniques and devices may prove useful in overcoming age- and disease-related losses in sensorimotor function IN linear information theory , electrical engineering and neurobiology , r and om noise has traditionally been viewed as a detriment to information transmission . Stochastic resonance ( SR ) is a nonlinear , statistical dynamics whereby information flow in a multistate system is enhanced by the presence of optimized , r and om noise14 . A major consequence of SR for signal reception is that it makes possible substantial improvements in the detection of weak periodic signals . Although SR has recently been demonstrated in several artificial physical systems5,6 , it may also occur naturally , and an intriguing possibility is that biological systems have evolved the capability to exploit SR by optimizing endogenous sources of noise . Sensory systems are an obvious place to look for SR , as they excel at detecting weak signals in a noisy environment . Here we demonstrate SR using external noise applied to crayfish mechanoreceptor cells . Our results show that individual neurons can provide a physiological substrate for SR in sensory systems This study investigated the effects on st and ing balance of r and om vibrations applied to the plantar side of the feet by vibrating insoles in subjects with neuropathy and nondisabled subjects . In four different conditions ( eyes open or closed and with or without an attention-dem and ing task [ ATD ] ) , subjects with neuropathy secondary to diabetes mellitus ( n = 17 ) and nondisabled subjects ( n = 15 ) stood for 60 s on vibrating insoles placed on a force plate . During each condition , the insoles were turned on for 30 s and off for 30 s ( r and om order ) . The calculated balance measures were mean velocity of the center of pressure displacements and root-mean-square of the velocity of these displacements in the anteroposterior and mediolateral directions . In subjects with neuropathy , an interaction effect between vibration and an ADT was found for balance . No effects of vibration on balance were found in nondisabled subjects . Vibrating insoles improved st and ing balance in subjects with neuropathy only when attention was distracted . Improvement of the insoles and their activation is needed to make their implementation in daily living possible and effective Noise is usually thought of as the enemy of order rather than as a constructive influence . In nonlinear systems that possess some sort of threshold , r and om noise plays a beneficial role in enhancing the detection of weak information-carrying signals . This phenomenon , termed stochastic resonance , does find useful applications in physical , biological , and biomedical context s. Certain biological systems may even use this effect for optimizing function and behavior OBJECTIVE The objective of the present study was to investigate the impact of incident falls on the balance , gait , and Activities of Daily Living functioning in community-dwelling older adults . METHODS This was a population -based , 1-year prospect i ve cohort study in older adults . We performed baseline assessment of potential predictors , the 1-year occurrence of falls , and then 1-year re assessment of the following outcome measures : the Barthel Index ( BI ) , Lawton 's Instrumental Activities of Daily Living ( IADL ) scale , gait speed , and Tinetti Balance and Gait Evaluation 's total mobility score ( TMS ) . At 1 year of follow-up , participants who had declined by > or = 1 st and ard deviation ( SD ) below the baseline mean value of each outcome measure were classified as " decliners . " RESULTS Of the 1517 participants , 93.5 % ( n = 1419 ) completed the 1-year follow-up re assessment of BI and IADL . For gait speed and TMS , respectively , 88.2 % ( n = 1338 ) and 88.3 % ( n = 1339 ) completed the 1-year outcome assessment . Fallers , particularly recurrent fallers , experienced significantly greater 1-year declines in the four functional measures . Multivariate logistic regression analyses showed that an incident fall was a significant independent predictor for decliners in the BI , Lawton 's IADL score , gait speed , and TMS after adjustment of all significant confounding factors . The relative risks of an incident fall as an independent predictor for decliners in the BI , IADL score , gait speed , and TMS were 2.4 ( 95 % confidence interval [ CI ] , 1.4 - 4.0 ; p = .01 ) , 2.9 ( 95 % CI , 1.7 - 5.2 ; p < .001 ) , 2.4 ( 95 % CI , 1.5 - 3.8 ; p < .001 ) , and 4.6 ( 95 % CI , 2.7 - 7.8 ; p < .001 ) , respectively . CONCLUSIONS Incident falls have a significant negative impact on the balance , gait , and Activities of Daily Living functioning in community-dwelling older adults OBJECTIVE To test the hypothesis that shoes with thick , soft midsoles , such as modern running shoes , provide better stability in older individuals than those with thin-hard midsoles . In addition , we examined the relation between footwear comfort and stability and stability when barefoot . DESIGN R and omized-order , cross-over , controlled comparison . SETTING Subjects were drawn from an internal medicine practice . PARTICIPANTS A r and om sample of 25 healthy men , minimum age 60 years . Additional selection criteria were absence of disabilities influencing ability to walk and lack of history of frequent falls . MEASUREMENTS Balance failure frequency , which was defined as falls from the beam per 100 meters of beam walking when 10 passes were made down a 9 M long balance beam . Comfort rating was based on an ordinal scale . RESULTS Contrary to the hypothesis : ( 1 ) midsole softness was associated with poor stability ( F(2,48 ) = 17.9 , P < 0.0001 ) ; ( 2 ) thick midsoles also provided poor stability ( F(1,24 ) = 7.36 , P < 0.01 ) . When barefoot , subjects showed 19 % higher balance failure frequency than with the poorest shoe and 171 % greater than the best shoe ( t = 5.33 , P < 0.0001 ) . Higher comfort was generally found in shoe types associated with higher balance failure frequency . CONCLUSIONS For optimal stability , shoes with thin , hard soles are preferable for older individuals . Health professionals should exercise caution when recommending shoes with thick , yielding midsoles , such as running shoes , to unstable elderly individuals . Older men and women with a history of falls or who are obviously unstable , should avoid barefoot locomotion OBJECTIVE To test the hypothesis that increased gait variability predicts falls among community-living older adults attending an outpatient clinic . DESIGN Prospect i ve , cohort study . SETTING Three outpatient geriatric clinics . PARTICIPANTS Fifty-two community-living , ambulatory men and women aged > or = 70 years . INTERVENTIONS Not applicable . MAIN OUTCOME MEASURES Subjects walked at a normal pace for up to 6 minutes wearing force-sensitive insoles that measured the gait rhythm on a stride-to-stride basis . Afterward , subjects reported fall status on a weekly basis for 1 year . The primary outcomes were the association between measures of the stride-to-stride fluctuations in gait rhythm and ( 1 ) subsequent falls during a 12-month follow-up period and ( 2 ) potential contributing factors . RESULTS Almost 40 % of the subjects reported falling during the 12-month follow-up period . Stride time variability was 106 + /- 30 ms in subjects who subsequently fell ( n = 20 ) and 49 + /- 4 ms in those who did not experience a fall ( n = 32 ) during the 12-month follow-up period ( p < .04 ) . Logistic regression also showed that stride time variability predicted falls ( p < .05 ) . Stride time variability correlated significantly with multiple factors including strength , balance , gait speed , functional status , and even mental health , but these other measures did not discriminate future fallers from nonfallers . CONCLUSIONS These findings show both the feasibility of obtaining stride-to-stride measures of gait timing in the ambulatory setting and the potential use of gait variability measures in augmenting the prospect i ve evaluation of fall risk in community-living older adults OBJECTIVE We have previously demonstrated that high plantar pressures can predict foot ulceration in diabetic patients . The aim of the present study was to evaluate both the relationship between forefoot and rearfoot plantar pressure in diabetic patients with different degrees of peripheral neuropathy and their role in ulcer development . RESEARCH DESIGN AND METHODS Diabetic patients of a 30-month prospect i ve study were classified according to the neuropathy disability score : scores of 0 , 1 - 5 , 6 - 16 , and 17 - 28 are defined as absent ( n = 20 ) , mild ( n = 66 ) , moderate ( n = 95 ) , and severe ( n = 57 ) neuropathy , respectively . The F-Scan mat system was used to measure dynamic plantar pressures . The peak pressures under the forefoot and the rearfoot were selectively measured for each foot , and the forefoot-to-rearfoot ratio ( F/R ratio ) was calculated . RESULTS Foot ulcers developed in 73 ( 19 % ) feet . The peak pressures were increased in the forefoot of the severe and moderate neuropathic groups compared with the mild neuropathic and non-neuropathic groups ( 6.2 + /- 4.5 and 3.8 + /- 2.7 vs. 3.0 + /- 2.1 and 3.3 + /- 2.1 kg/cm(2 ) [ mean + /- SD ] , respectively ; P < 0.0001 ) . The rearfoot pressures were also higher in the severe and moderate neuropathic groups compared with the mild neuropathic and non-neuropathic groups ( 3.2 + /- 2.0 and 3.2 + /- 1.9 vs. 2.5 + /- 1.3 and 2.3 + /- 1.0 , respectively ; P < 0.0001 ) . The F/R ratio was increased only in the severe group compared with the moderate and mild neuropathic and non-neuropathic groups ( 2.3 + /- 2.4 vs. 1.5 + /- 1.2 , 1.3 + /- 0.9 , and 1.6 + /- 1.0 , respectively ; P < 0.0001 ) . In a logistic regression analysis , both forefoot pressure ( odds ratio 1.19 [ 95 % CI 1.11 - 1.28 ] , P < 0.0001 ) and the F/R ratio ( 1.37 [ 1.16 - 1.61 ] , P < 0.0001 ) were related to risk of foot ulceration , whereas rearfoot pressure was not . CONCLUSIONS Both the rearfoot and forefoot pressures are increased in the diabetic neuropathic foot , whereas the F/R ratio is increased only in severe diabetic neuropathy , indicating an imbalance in pressure distribution with increasing degrees of neuropathy . This may lend further evidence toward the concept that equinus develops in the latest stages of peripheral neuropathy and may play an important role in the etiology of diabetic foot ulceration Acute application of stochastic resonance ( SR ) , defined as a subsensory level of mechanical noise presented directly to sensory neurons , improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy . This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function . Twenty diabetic patients were studied . The effect of stimulation was measured at 2 time points , at the beginning and after 60 minutes of continual SR stimulation . This effect was measured using the vibration perception threshold ( VPT ) at the big toe under 2 conditions : a null ( no SR ) condition and active SR , defined as mechanical noise below the subject 's own threshold of perception . The measurements under null and active conditions were done r and omly and the examiner was blinded regarding the type of condition . Immediately after SR application , the VPT with SR in null condition was similar to baseline ( 32.2 ± 13.1 , P = nonsignificant ) but was significantly lower during active SR ( 27.4 ± 11.9 ) compared with both baseline ( P = .018 ) and off position ( P = .045 ) . The 60 minutes VPT with active SR ( 28.7 ± 11.1 ) reached significance comparing the baseline when one outlier was removed from the analysis ( P = .031 ) . It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy . These results permit the conclusion that there is no short-term adaptation to the stimulation signal . Long-term application of this technique , perhaps in the form of a continually vibrating shoe insert , or insole , may result in sustained improvement of nerve function 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 . The aim of the present study was to investigate the influence of reduced plantar sensation on pressure distribution patterns during gait of 40 healthy subjects ( 25.3+/-3.3 yr , 70.8+/-10.6 kg and 176.5+/-7.8 cm ) with no history of sensory disorders . Plantar sensation in the subjects was reduced by using an ice immersion approach , and reduced sensitivity was tested with Semmes-Weinstein monofilaments . All subjects performed six trials of barefoot walking over a pressure distribution platform under normal as well as iced conditions . Plantar cutaneous sensation was significantly reduced after the cooling procedure ( p<0.0001 ) . Pressure distribution analysis showed substantially modified plantar pressure distribution patterns during the roll-over process ( ROP ) under iced conditions . Analysis of peak pressures revealed significant reductions under the toes and under the heel ( p<0.001 ) . The contact time and the relative impulse for the whole foot did not change significantly between the two conditions . For the different areas , a significant load shift from the heel and toes towards the central and lateral forefoot and the lateral midfoot was observed . The results indicate the strong influence of reduced afferent information of the sole of the foot on the ROP in walking OBJECTIVE To determine , in a cohort of ambulatory older adults , whether spatial-temporal measures of foot placement during gait can predict the likelihood of future falls or whether these measures are more likely to be indicative of adaptations associated with pre-existing fear of falling . DESIGN Prospect i ve cohort study . SETTING Baseline gait measurements were performed in a gait and balance laboratory ; subsequent history of falling was monitored prospect ively for 1 year in two self-care facilities . PARTICIPANTS Fourteen male and 61 female consecutive volunteers ( mean age = 82 , SD = 6 ) who were independent in activities of daily living and able to walk 10 m unaided . MEASUREMENTS Spatial gait parameters were derived from digitized " footprints " ; temporal parameters were derived using footswitches . A clinical activity-based gait assessment was also performed . The dependent variables were pre-existing fear of falling ( reported at baseline ) and future falling ( experiencing one or more falls during the 1-year follow-up ) . MAIN RESULTS Reduced stride length , reduced speed , increased double-support time , and poorer clinical gait scores were associated with fear but showed little evidence of an independent association with falling . Conversely , increased stride-to-stride variability in stride length , speed , and double-support was associated independently with falling but showed little evidence of relationship to fear . Increased stride width showed some evidence of association with both falling and fear . Stride-to-stride variability in speed was the single best independent predictor of falling . CONCLUSIONS Changes in gait cited previously as risk factors for falling , i.e. , decreased stride length and speed and prolonged double support , may in fact be stabilizing adaptations related to fear of falling . Stride-to-stride variability in the control of gait is an independent predictor of falling and may be a useful measure for identifying high-risk individuals and evaluating preventive interventions . Stride width may also be a useful outcome measure . Contrary to common expectation , a wider stride does not necessarily increase stability but instead seems to predict an increased likelihood of experiencing falls This study employed manipulation of sensory inputs ( vision and plantar-surface cutaneous sensation ) during gait termination to elicit insight into the roles played by these sensory systems in the control of gait termination . Attenuation of cutaneous sensation was achieved through hypothermic anesthesia . Visual information was occluded using special glasses . The subjects were asked to walk along an 8 m walkway and during r and omly selected trials ( 25 % of trials ) to terminate their gait in a predetermined area . The centre of mass ( COM ) was obtained in order to provide an indication of the efficiency and stability during termination when sensory inputs were manipulated . Lack of visual information delayed the initiation of the slowing down of the COM forward progression and increased the step length of the last step of termination . Additionally , lack of vision result ed in the COM moving closer to the base of support ( BOS ) during double support and more variability , in the COM , when attempting to achieve a final stable position . Insensitivity of the plantar-surface mechanoreceptors led to a longer second step and a more variable foot placement of the first step , and increased the loading rate during the final two steps of termination . Additionally when vision and cutaneous information were absent the resolution of the final stable position was not as effectively controlled . The results demonstrated that visual information about self-motion and object-motion and sensation from the plantar surface of the foot play phase-specific roles in the control of COM during gait termination Somatosensory function declines with age , and such changes have been associated with diminished motor performance . Input noise can enhance sensory and motor function . We asked young and elderly participants to st and quietly on vibrating gel-based insoles , and calculated sway parameters and r and om-walk variables . In our 27 participants , application of noise result ed in a reduction in seven of eight sway parameters in young participants and all of the sway variables in elderly participants . Elderly participants showed greater improvement than young people in two variables , mediolateral range ( p=0.008 ) , and critical mean square displacement ( p=0.012 ) . Noise-based devices , such as r and omly vibrating insoles , could ameliorate age-related impairments in balance control The purpose of this study was to determine whether providing subsensory stochastic-resonance mechanical vibration to the foot soles of elderly walkers could decrease gait variability . In a r and omized double-blind controlled trial , 29 subjects engaged in treadmill walking while wearing s and als customized with three actuators capable of producing stochastic-resonance mechanical vibration embedded in each sole . For each subject , we determined a subsensory level of vibration stimulation . After a 5-min acclimation period of walking with the footwear , subjects were asked to walk on the treadmill for six trials , each 30s long . Trials were pair-wise r and om : in three trials , actuators provided subsensory vibration ; in the other trials , they did not . Subjects wore reflective markers to track body motion . Stochastic-resonance mechanical stimulation exhibited baseline-dependent effects on spatial stride-to-stride variability in gait , slightly increasing variability in subjects with least baseline variability and providing greater reductions in variability for subjects with greater baseline variability ( p<.001 ) . Thus , applying stochastic-resonance mechanical vibrations on the plantar surface of the foot reduces gait variability for subjects with more variable gait . Stochastic-resonance mechanical vibrations may provide an effective intervention for preventing falls in healthy elderly walkers A significant predictor of falls in the elderly population is attributed to postural instability . Thus , it is important to identify and implement practical clinical interventions to enhance postural stability in older adults . Shoe insoles have been identified as a mechanism to enhance postural control , and our study aim ed to evaluate the impact of 2 shoe insoles on static st and ing balance in healthy , older adults compared with st and ing posture while barefoot . We hypothesized that both hard and soft shoe insoles would decrease postural sway compared with the barefoot condition . Indeed , excursion distances and sway areas were reduced , and sway velocity was decreased when wearing insoles . The hard insole was also effective when visual feedback was removed , suggesting that the more rigid an insole , the greater potential reduction in fall risk . Thus , shoe insoles may be a cost-effective , clinical intervention that is easy to implement to reduce the risk of falling in the elderly population |
12,882 | 26,968,879 | Web-based interventions have the potential to improve the cardiovascular risk profile of older people , but the effects are modest and decline with time .
Currently , there is insufficient evidence for an effect on incident cardiovascular disease . | BACKGROUND Web-based interventions can improve single cardiovascular risk factors in adult population s. In view of global aging and the associated increasing burden of cardiovascular disease , older people form an important target population as well .
OBJECTIVE In this systematic review and meta- analysis , we evaluated whether Web-based interventions for cardiovascular risk factor management reduce the risk of cardiovascular disease in older people . | Objective : We sought to assess whether either a low-cost educational intervention or small monetary incentive is more effective than usual care in lowering low-density lipoprotein ( LDL ) cholesterol among employees . Methods : Employees with an LDL-C > 130 mg/dL were eligible . After receiving on-line educational material s , subjects were assigned to three groups : group 1 received $ 100 if they reduced their LDL-C by 15 % within 6 months , group 2 participated in a multi-disciplinary educational program , and group 3 received no further intervention . Results : In total , 171 employees participated . Baseline mean LDL-C was 156 mg/dL. Approximately 6 months after r and omization , mean LDL-C was reduced 17.9 mg/dL ( 11.3 % ) in group 1 , 17.9 mg/dL ( 11.5 % ) in group 2 , and 5.5 mg/dL ( 3.5 % ) in group 3 . Reductions in groups 1 and 2 were statistically superior to group 3 ( P = 0.02 ) . Conclusions : Both an employer directed low-cost educational program and small monetary incentives similarly lowered LDL-C compared with usual care OBJECTIVE To assess the effects of web-based care management on glucose and blood pressure control over 12 months in patients with poorly controlled diabetes . RESEARCH DESIGN AND METHODS For this study , 104 patients with diabetes and HbA(1c ) ( A1C ) > or = 9.0 % who received their care at a Department of Veterans Affairs medical center were recruited . All participants completed a diabetes education class and were r and omized to continue with their usual care ( n = 52 ) or receive web-based care management ( n = 52 ) . The web-based group received a notebook computer , glucose and blood pressure monitoring devices , and access to a care management website . The website provided educational modules , accepted uploads from monitoring devices , and had an internal messaging system for patients to communicate with the care manager . RESULTS Participants receiving web-based care management had lower A1C over 12 months ( P < 0.05 ) when compared with education and usual care . Persistent website users had greater improvement in A1C when compared with intermittent users ( -1.9 vs. -1.2 % ; P = 0.051 ) or education and usual care ( -1.4 % ; P < 0.05 ) . A larger number of website data uploads was associated with a larger decline in A1C ( highest tertile -2.1 % , lowest tertile -1.0 % ; P < 0.02 ) . Hypertensive participants in the web-based group had a greater reduction in systolic blood pressure ( P < 0.01 ) . HDL cholesterol rose and triglycerides fell in the web-based group ( P < 0.05 ) . CONCLUSIONS Web-based care management may be a useful adjunct in the care of patients with poorly controlled diabetes Aim To determine the effectiveness and cost-effectiveness of a mobile phone intervention to improve exercise capacity and physical activity behaviour in people with ischaemic heart disease ( IHD ) . Methods and results In this single-blind , parallel , two-arm , r and omized controlled trial adults ( n = 171 ) with IHD were r and omized to receive a mobile phone delivered intervention ( HEART ; n = 85 ) plus usual care , or usual care alone ( n = 86 ) . Adult participants aged 18 years or more , with a diagnosis of IHD , were clinical ly stable as out patients , able to perform exercise , able to underst and and write English , and had access to the Internet . The HEART ( Heart Exercise And Remote Technologies ) intervention involved a personalized , automated package of text messages and a secure website with video messages aim ed at increasing exercise behaviour , delivered over 24 weeks . All participants were able to access usual community-based cardiac rehabilitation , which involves encouragement of physical activity and an offer to join a local cardiac support club . All outcomes were assessed at baseline and 24 weeks and included peak oxygen uptake ( PVO2 ; primary outcome ) , self-reported physical activity , health-related quality of life , self-efficacy and motivation ( secondary outcomes ) . Results showed no differences in PVO2 between the two groups ( difference −0.21 ml kg−1 min−1 , 95 % CI : −1.1 , 0.7 ; p = 0.65 ) at 24 weeks . However significant treatment effects were observed for selected secondary outcomes , including leisure time physical activity ( difference 110.2 min/week , 95 % CI : −0.8 , 221.3 ; p = 0.05 ) and walking ( difference 151.4 min/week , 95 % CI : 27.6 , 275.2 ; p = 0.02 ) . There were also significant improvements in self-efficacy to be active ( difference 6.2 % , 95 % CI : 0.2 , 12.2 ; p = 0.04 ) and the general health domain of the SF36 ( difference 2.1 , 95 % CI : 0.1 , 4.1 ; p = 0.03 ) at 24 weeks . The HEART programme was considered likely to be cost-effective for leisure time activity and walking . Conclusions A mobile phone intervention was not effective at increasing exercise capacity over and above usual care . The intervention was effective and probably cost-effective for increasing physical activity and may have the potential to augment existing cardiac rehabilitation services Background Age‐related endothelial dysfunction and vascular stiffening are associated with increased cardiovascular ( CV ) risk . Many groups have encouraged goals of ≥10 000 steps/day or ≥30 min/day of moderate intensity physical activity ( MPA ) to reduce age‐related CV risk . The impact of MPA on the vasculature of older adults remains unclear . Methods and Results We r and omized 114 sedentary older adults ages ≥50 to 12 weeks of either no intervention ( group 1 ) , a pedometer‐only intervention ( group 2 ) , or a pedometer with an interactive website employing strategies to increase the adoption of habitual physical activity ( PA , group 3 ) . Endothelial function by brachial flow‐mediated dilation ( FMD% ) , vascular stiffness by tonometry , step‐count by pedometer , and PA intensity/distribution by accelerometer were measured . Step‐count increased in groups 2 ( 5136±1554 to 9596±3907 , P<0.001 ) and 3 ( 5474±1512 to 8167±3111 , P<0.001 ) but not in group 1 ( 4931±1667 to 5410±2410 ) . Both groups 2 and 3 increased MPA ≥30 min/day . Only group 3 increased MPA in continuous bouts of ≥10 minutes ( P<0.001 ) and improved FMD% ( P=0.001 ) . Neither achievement of ≥10 000 steps/day nor ≥30 min/day of MPA result ed in improved FMD% . However , achieving ≥20 min/day in MPA bouts result ed in improved FMD% . No changes in vascular stiffness were observed . Conclusions MPA reverses age‐related endothelial dysfunction , but may require MPA to be performed in bouts of ≥10 minutes duration for ≥20 min/day to be effective . Commonly encouraged PA goals do not guarantee improved endothelial function and may not be as effective in reducing CV risk . Clinical Trial Registration URL : Clinical trials.gov . Unique identifier : NCT‐01212978 BACKGROUND Web-based interventions for weight control could promote more-widespread dissemination of weight-loss opportunities ; however , they remain limited in effectiveness . Incorporating weight-control practice s used by individuals with long-term weight-loss success ( " positive deviants " ) may improve the efficacy of web-based weight control interventions . PURPOSE To evaluate the efficacy of AchieveTogether , a web-based weight-loss intervention for adults based on user-generated weight-loss strategies from successful weight losers . DESIGN In 2009 - 2010 , participants were r and omized to either a 12-week web-based intervention , AchieveTogether , or a wait-list control condition . SETTING / PARTICIPANTS 100 overweight or obese adults participated in the study . INTERVENTION AchieveTogether was design ed to help individuals implement weight control practice s used by others who successfully lost and maintained weight . MAIN OUTCOME MEASURES The primary outcome was change in weight . Secondary outcomes included blood pressure , daily caloric intake , quality of life , and use of weight control practice s. ANCOVA , with adjustment for baseline values on outcome measures , was used to assess differences between groups in primary and secondary outcomes . Statistical analyses were conducted in 2010 - 2011 . RESULTS Most participants were women ( 69.7 % ) and white ( 90.8 % ) , with a mean age of 50.3 years and baseline BMI of 33.2 ; 88 % completed post-program assessment s. Mean weight loss among intervention participants was -1.4 kg ( 95 % CI= -2.2 , -0.5 ) , compared with a mean weight gain of 0.6 kg ( 95 % CI= -0.3 , 1.4 ) in control participants ( p<0.01 ) . CONCLUSIONS User-generated weight-loss practice s from " positive deviants " could promote weight control in web-based interventions ; however , further research is needed to improve program efficacy . TRIAL REGISTRATION This study is registered at Clinical Trials.govNCT00709501 Background : The CardioFit internet-based expert system was design ed to promote physical activity in patients with coronary heart disease ( CHD ) who were not participating in cardiac rehabilitation . Design : This r and omized controlled trial compared CardioFit to usual care to assess its effects on physical activity following hospitalization for acute coronary syndromes . Methods : A total of 223 participants were recruited at the University of Ottawa Heart Institute or London Health Sciences Centre and r and omly assigned to either CardioFit ( n = 115 ) or usual care ( n = 108 ) . The CardioFit group received a personally tailored physical-activity plan upon discharge from the hospital and access to a secure website for activity planning and tracking . They completed five online tutorials over a 6-month period and were in email contact with an exercise specialist . Usual care consisted of physical activity guidance from an attending cardiologist . Physical activity was measured by pedometer and self-reported over a 7-day period , 6 and 12 months after r and omization . Results : The CardioFit internet-based physical activity expert system significantly increased objective ly measured ( p = 0.023 ) and self-reported physical activity ( p = 0.047 ) compared to usual care . Emotional ( p = 0.038 ) and physical ( p = 0.031 ) dimensions of heart disease health-related quality of life were also higher with CardioFit compared to usual care . Conclusions : Patients with CHD using an internet-based activity prescription with online coaching were more physically active at follow up than those receiving usual care . Use of the CardioFit program could extend the reach of rehabilitation and secondary -prevention services OBJECTIVE To test whether adding mobile application coaching and patient/provider web portals to community primary care compared with st and ard diabetes management would reduce glycated hemoglobin levels in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS A cluster-r and omized clinical trial , the Mobile Diabetes Intervention Study , r and omly assigned 26 primary care practice s to one of three stepped treatment groups or a control group ( usual care ) . A total of 163 patients were enrolled and included in analysis . The primary outcome was change in glycated hemoglobin levels over a 1-year treatment period . Secondary outcomes were changes in patient-reported diabetes symptoms , diabetes distress , depression , and other clinical ( blood pressure ) and laboratory ( lipid ) values . Maximal treatment was a mobile- and web-based self-management patient coaching system and provider decision support . Patients received automated , real-time educational and behavioral messaging in response to individually analyzed blood glucose values , diabetes medications , and lifestyle behaviors communicated by mobile phone . Providers received quarterly reports summarizing patient ’s glycemic control , diabetes medication management , lifestyle behaviors , and evidence -based treatment options . RESULTS The mean declines in glycated hemoglobin were 1.9 % in the maximal treatment group and 0.7 % in the usual care group , a difference of 1.2 % ( P = 0.001 ) over 12 months . Appreciable differences were not observed between groups for patient-reported diabetes distress , depression , diabetes symptoms , or blood pressure and lipid levels ( all P > 0.05 ) . CONCLUSIONS The combination of behavioral mobile coaching with blood glucose data , lifestyle behaviors , and patient self-management data individually analyzed and presented with evidence -based guidelines to providers substantially reduced glycated hemoglobin levels over 1 year Objective To investigate whether an internet based , nurse led vascular risk factor management programme promoting self management on top of usual care is more effective than usual care alone in reducing vascular risk factors in patients with clinical ly manifest vascular disease . Design Prospect i ve r and omised controlled trial . Setting Multicentre trial in secondary and tertiary healthcare setting . Participants 330 patients with a recent clinical manifestation of atherosclerosis in the coronary , cerebral , or peripheral arteries and with at least two treatable risk factors not at goal . Intervention Personalised website with an overview and actual status of patients ’ risk factors and mail communication via the website with a nurse practitioner for 12 months ; the intervention combined self management support , monitoring of disease control , and drug treatment . Main outcome measures The primary endpoint was the relative change in Framingham heart risk score after 1 year . Secondary endpoints were absolute changes in the levels of risk factors and the differences between groups in the change in proportion of patients reaching treatment goals for each risk factor . Results Participants ’ mean age was 59.9 ( SD 8.4 ) years , and most patients ( n=246 ; 75 % ) were male . After 1 year , the relative change in Framingham heart risk score of the intervention group compared with the usual care group was −14 % ( 95 % confidence interval −25 % to −2 % ) . At baseline , the Framingham heart risk score was higher in the intervention group than in the usual care group ( 16.1 ( SD 10.6 ) v 14.0 ( 10.5 ) ) , so the outcome was adjusted for the separate variables of the Framingham heart risk score and for the baseline Framingham heart risk score . This produced a relative change of −12 % ( −22 % to −3 % ) in Framingham heart risk score for the intervention group compared with the usual care group adjusted for the separate variables of the score and −8 % ( −18 % to 2 % ) adjusted for the baseline score . Of the individual risk factors , a difference between groups was observed in low density lipoprotein cholesterol ( −0.3 , −0.5 to −0.1 , mmol/L ) and smoking ( −7.7 % , −14.9 % to −0.4 % ) . Some other risk factors tended to improve ( body mass index , triglycerides , systolic blood pressure , renal function ) or tended to worsen ( glucose concentration , albuminuria ) . Conclusion An internet based , nurse led treatment programme on top of usual care for vascular risk factors had a small effect on lowering vascular risk and on lowering of some vascular risk factors in patients with vascular disease . Trial registration Clinical trials NCT00785031 Background Angina affects more than 50 million people worldwide . Secondary prevention interventions such as cardiac rehabilitation are not widely available for this population . An Internet-based version could offer a feasible alternative . Objective Our aim was to examine the effectiveness of a Web-based cardiac rehabilitation program for those with angina . Methods We conducted a r and omized controlled trial , recruiting those diagnosed with angina from general practitioners ( GPs ) in primary care to an intervention or control group . Intervention group participants were offered a 6-week Web-based rehabilitation program ( “ ActivateYourHeart ” ) . The program was introduced during a face-to-face appointment and then delivered via the Internet ( no further face-to-face contact ) . The program contained information about the secondary prevention of coronary heart disease ( CHD ) and set each user goals around physical activity , diet , managing emotions , and smoking . Performance against goals was review ed throughout the program and goals were then reset/modified . Participants completed an online exercise diary and communicated with rehabilitation specialists through an email link/synchronized chat room . Participants in the control group continued with GP treatment as usual , which consisted of being placed on a CHD register and attending an annual review . Outcomes were measured at 6-week and 6-month follow-ups during face-to-face assessment s. The primary outcome measure was change in daily steps at 6 weeks , measured using an accelerometer . Secondary outcome measures were energy expenditure ( EE ) , duration of sedentary activity ( DSA ) , duration of moderate activity ( DMA ) , weight , diastolic/systolic blood pressure , and body fat percentage . Self-assessed question naire outcomes included fat/fiber intake , anxiety/depression , self-efficacy , and quality of life ( QOL ) . Results A total of 94 participants were recruited and r and omized to the intervention ( n=48 ) or the usual care ( n=46 ) group ; 84 and 73 participants completed the 6-week and 6-month follow-ups , respectively . The mean number of log-ins to the program was 18.68 ( SD 13.13 , range 1 - 51 ) , an average of 3 log-ins per week per participant . Change in daily steps walked at the 6-week follow-up was + 497 ( SD 2171 ) in the intervention group and –861 ( SD 2534 ) in the control group ( 95 % CI 263 - 2451 , P=.02 ) . Significant intervention effects were observed at the 6-week follow-up in EE ( + 43.94 kcal , 95 % CI 43.93 - 309.98 , P=.01 ) , DSA ( –7.79 minutes , 95 % CI –55.01 to –7.01 , P=.01 ) , DMA ( + 6.31 minutes , 95 % CI 6.01 - 51.20 , P=.01 ) , weight ( –0.56 kg , 95 % CI –1.78 to –0.15 , P=.02 ) , self-efficacy ( 95 % CI 0.30 - 4.79 , P=.03 ) , emotional QOL score ( 95 % CI 0.01 - 0.54 , P=.04 ) , and angina frequency ( 95 % CI 8.57 - 35.05 , P=.002 ) . Significant benefits in angina frequency ( 95 % CI 1.89 - 29.41 , P=.02 ) and social QOL score ( 95 % CI 0.05 - 0.54 , P=.02 ) were also observed at the 6-month follow-up . Conclusions An Internet-based secondary prevention intervention could be offered to those with angina . A larger pragmatic trial is required to provide definitive evidence of effectiveness and cost-effectiveness . Trial Registration International St and ard R and omized Controlled Trial Number ( IS RCT N ) : 90110503 ; http://www.controlled-trials.com/IS RCT N90110503/IS RCT N90110503 ( Archived by WebCite at http://www.webcitation.org/6RYVOQFKM ) Background : Theory-based interventions accessible to large groups of people are needed to induce favorable shifts in health behaviors and body weight . Purpose : The aim was to assess nutrition ; physical activity ; and , secondarily , body weight in the tailored , social cognitive Guide to Health ( GTH ) Internet intervention delivered in churches . Methods : Participants ( N=1,071 ; 33 % male , 23 % African American , 57 % with body mass index ≥25 , 60 % sedentary , Mdn age=53 years ) within 14 Baptist or United Method ist churches were r and omized to the GTH intervention only ( GTH-Only ; 5 churches ) , with church-based supports ( GTH-Plus ; 5 churches ) , or to a waitlist ( control ; 4 churches ) . Verified pedometer step counts , measured body weight , fat , fiber , and fruit and vegetable ( F&V ) servings from food frequency and supermarket receipts were collected at pretest , posttest ( 7 months after pretest ) , and follow-up ( 16 months after pretest ) . Results : Participants in GTH-Only increased F&V at post ( ∼1.50 servings ) compared to control ( ∼0.50 servings ; p=.005 ) and at follow-up ( ∼1.20 vs. ∼0.50 servings ; p=.038 ) and increased fiber at post ( ∼3.00 g ) compared to control ( ∼1.5 g ; p=.006 ) and follow-up ( ∼3.00 g vs. ∼2.00 g ; p=.040 ) . GTH-Plus participants compared to control increased steps at post ( ∼1,500 steps/day vs. ∼400 steps/day ; p=.050 ) and follow-up ( ∼1,000 steps/day vs. ∼−50 steps/day ; p=.010 ) , increased F&V at post ( ∼1.5 servings ; p=.007 ) and follow-up ( ∼1.3 servings ; p=.014 ) , increased fiber at post ( ∼3.00 g ; p=.013 ) , and follow-up ( ∼3.00 ; p=.050 ) and decreased weight at post ( ∼−0.30 kg vs. ∼+0.60 kg ; p=.030 ) . Conclusions : Compared to control , both GTH treatments improved nutrition at posttest , but church supports improved physical activity and nutrition at posttest and follow-up , suggesting environmental supports may improve Internet-based interventions Background Only approximately half of patients with hypertension have their blood pressure controlled , due in large part to the tendency of primary care providers ( PCPs ) not to intensify treatment when blood pressure values are elevated . Objective This study tested the effect of an intervention design ed to help patients ask questions at the point of care to encourage PCPs to appropriately intensify blood pressure treatment . Methods PCPs and their patients with hypertension ( N=500 ) were recruited by letter and r and omized into 2 study groups : ( 1 ) intervention condition in which patients used a fully automated website each month to receive tailored messages suggesting questions to ask their PCP to improve blood pressure control , and ( 2 ) control condition in which a similar tool suggested questions to ask about preventive services ( eg , cancer screening ) . The Web-based tool was design ed to be used during each of the 12 study months and before scheduled visits with PCPs . The primary outcome was the percentage of patients in both conditions with controlled blood pressure . Results Of 500 enrolled patients ( intervention condition : n=282 ; control condition : n=218 ) , 418 ( 83.6 % ) completed the 12-month follow-up visit . At baseline , 289 ( 61.5 % ) of participants had controlled blood pressure . Most ( 411/500 , 82.2 % ) participants used the intervention during at least 6 of 12 months and 222 ( 62.5 % ) reported asking questions directly from the Web-based tool . There were no group differences in asking about medication intensification and there were no differences in blood pressure control after 12 months between the intervention condition ( 201/282 , 71.3 % ) and control condition ( 143/218 , 65.6 % ; P=.27 ) groups . More intervention condition participants discussed having a creatinine test ( 92 , 52.6 % vs 49 , 35.5 % ; P=.02 ) and urine protein test ( 81 , 44.8 % vs 21 , 14.6 % ; P<.001 ) , but no group differences were observed in the rate of testing . The control condition participants reported more frequent discussion s about tetanus and pneumonia vaccines and reported more tetanus ( 30 , 13.8 % vs 15 , 5.3 % ; P=.02 ) and pneumonia ( 25 , 11.5 % vs 16 , 5.7 % ; P=.02 ) vaccinations after 12 months . Conclusions The use of an interactive website design ed to overcome clinical inertia for hypertension care did not lead to improvements in blood pressure control . Participant adherence to the intervention was high . The control intervention led to positive changes in the use of preventive services ( eg , tetanus immunization ) and the intervention condition led to more discussion s of hypertension-relevant tests ( eg , serum creatinine and urine protein ) . By providing patients with individually tailored questions to ask during PCP visits , this study demonstrated that participants were likely to discuss the questions with PCPs . These discussion s did not , however , lead to improvements in blood pressure control . Trial Registration Clinical Trials.gov NCT00377208 ; http:// clinical trials.gov/ct2/show/NCT00377208 ( Archived by WebCite at http://www.webcitation.org/6IqWiPLon ) OBJECTIVE We hypothesized that people with type 2 diabetes in an online diabetes self-management program , compared with usual-care control subjects , would 1 ) demonstrate reduced A1C at 6 and 18 months , 2 ) have fewer symptoms , 3 ) demonstrate increased exercise , and 4 ) have improved self-efficacy and patient activation . In addition , participants r and omized to listserve reinforcement would have better 18-month outcomes than participants receiving no reinforcement . RESEARCH DESIGN AND METHODS A total of 761 participants were r and omized to 1 ) the program , 2 ) the program with e-mail reinforcement , or 3 ) were usual-care control subjects ( no treatment ) . This sample included 110 American Indians/Alaska Natives ( AI/ANs ) . Analyses of covariance models were used at the 6- and 18-month follow-up to compare groups . RESULTS At 6 months , A1C , patient activation , and self-efficacy were improved for program participants compared with usual care control subjects ( P < 0.05 ) . There were no changes in other health or behavioral indicators . The AI/AN program participants demonstrated improvements in health distress and activity limitation compared with usual-care control subjects . The subgroup with initial A1C > 7 % demonstrated stronger improvement in A1C ( P = 0.01 ) . At 18 months , self-efficacy and patient activation were improved for program participants . A1C was not measured . Reinforcement showed no improvement . CONCLUSIONS An online diabetes self-management program is acceptable for people with type 2 diabetes . Although the results were mixed they suggest 1 ) that the program may have beneficial effects in reducing A1C , 2 ) AI/AN population s can be engaged in and benefit from online interventions , and 3 ) our follow-up reinforcement appeared to have no value Background Physical activity ( PA ) for older adults has well-documented physical and cognitive benefits , but most seniors do not meet recommended guidelines for PA , and interventions are lacking . Objectives This study evaluated the efficacy of a 12-week Internet intervention to help sedentary older adults over 55 years of age adopt and maintain an exercise regimen . Methods A total of 368 sedentary men and women ( M=60.3 ; SD 4.9 ) were recruited , screened , and assessed online . They were r and omized into treatment and control groups and assessed at pretest , at 12 weeks , and at 6 months . After treatment group participants rated their fitness level , activity goals , and barriers to exercise , the Internet intervention program helped them select exercise activities in the areas of endurance , flexibility , strengthening , and balance enhancement . They returned to the program weekly for automated video and text support and education , with the option to change or increase their exercise plan . The program also included ongoing problem solving to overcome user-identified barriers to exercise . Results The multivariate model indicated significant treatment effects at posttest ( P=.001 ; large effect size ) and at 6 months ( P=.001 ; medium effect size ) . At posttest , intervention participation showed significant improvement on 13 of 14 outcome measures compared to the control participants . At 6 months , treatment participants maintained large gains compared to the control participants on all 14 outcome measures . Conclusions These results suggest that an online PA program has the potential to positively impact the physical activity of sedentary older adult participants . More research is needed to replicate the study results , which were based on self-report measures . Research is also needed on intervention effects with older population Background Diet is the first line of treatment for elevated cholesterol . High-intensity dietary counseling ( ≥360 minutes/year of contact with providers ) improves blood lipids , but is expensive and unsustainable in the current healthcare setting s. Low-intensity counseling trials ( ≤ 30 minutes/year ) have demonstrated modest diet changes , but no improvement in lipids . This pilot study evaluated the feasibility and the effects on lipids and diet of a low-intensity dietary counseling intervention provided by the primary care physician ( PCP ) , in patients at risk for cardiovascular diseases . Methods Six month study with a three month r and omized-controlled phase ( group A received the intervention , group B served as controls ) followed by three months of intervention in both groups . Sixty-one adults age 21 to 75 years , with LDL-cholesterol ≥ 3.37 mmol/L , possessing Internet access and active email accounts were enrolled . Diet was evaluated using the Rate-Your-Plate question naire . Dietary counseling was provided by the PCP during routine office visits , three months apart , using printed educational material s and a minimally interactive counseling website . Weekly emails were sent reminding participants to use the dietary counseling re sources . The outcomes were changes in LDL-cholesterol , other lipid subclasses , and diet quality . Results At month 3 , group A ( counseling started at month 1 ) decreased their LDL-cholesterol by −0.23 mmol/L , ( −0.04 to −0.42 mmol/L , P = 0.007 ) and total cholesterol by −0.26 mmol/L , ( −0.05 to −0.47 mmol/L , P = 0.001 ) . At month 6 , total and LDL-cholesterol in group A remained better than in group B ( counseling started at month 3 ) . Diet score in group A improved by 50.3 points ( 38.4 to 62.2 , P < 0.001 ) at month 3 ; and increased further by 11.8 ( 3.5 to 20.0 , P = 0.007 ) at month 6 . Group B made the largest improvement in diet at month 6 , 55 points ( 40.0 to 70.1 , P < 0.001 ) , after having a small but significant improvement at month 3 , 22.3 points ( 12.9 to 31.7 , P < 0.001 ) . No significant changes occurred in HDL-cholesterol in either group . Conclusions A low-intensity dietary counseling provided by the PCP in patients at risk for cardiovascular diseases produced clinical ly meaningful improvements in both diet and lipids of magnitude similar to changes reported with high intensity interventions .Trial registration Clinical Trials.gov : Background There is a need for cost-effective weight management interventions that primary care can deliver to reduce the morbidity caused by obesity . Automated web-based interventions might provide a solution , but evidence suggests that they may be ineffective without additional human support . The main aim of this study was to carry out a feasibility trial of a web-based weight management intervention in primary care , comparing different levels of nurse support , to determine the optimal combination of web-based and personal support to be tested in a full trial . Methods This was an individually r and omised four arm parallel non-blinded trial , recruiting obese patients in primary care . Following online registration , patients were r and omly allocated by the automated intervention to either usual care , the web-based intervention only , or the web-based intervention with either basic nurse support ( 3 sessions in 3 months ) or regular nurse support ( 7 sessions in 6 months ) . The main outcome measure ( intended as the primary outcome for the main trial ) was weight loss in kg at 12 months . As this was a feasibility trial no statistical analyses were carried out , but we present means , confidence intervals and effect sizes for weight loss in each group , uptake and retention , and completion of intervention components and outcome measures . Results All r and omised patients were included in the weight loss analyses ( using Last Observation Carried Forward ) . At 12 months mean weight loss was : usual care group ( n = 43 ) 2.44 kg ; web-based only group ( n = 45 ) 2.30 kg ; basic nurse support group ( n = 44 ) 4.31 kg ; regular nurse support group ( n = 47 ) 2.50 kg . Intervention effect sizes compared with usual care were : d = 0.01 web-based ; d = 0.34 basic nurse support ; d = 0.02 regular nurse support . Two practice s deviated from protocol by providing considerable weight management support to their usual care patients . Conclusions This study demonstrated the feasibility of delivering a web-based weight management intervention supported by practice nurses in primary care , and suggests that the combination of the web-based intervention with basic nurse support could provide an effective solution to weight management support in a primary care context .Trial registration Current Controlled Trials IS RCT N31685626 OBJECTIVE —To test Web-based care management of glycemic control using a shared electronic medical record with patients who have type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a trial of 83 adults with type 2 diabetes r and omized to receive usual care plus Web-based care management or usual care alone between August 2002 and May 2004 . All patients had GHb ≥7.0 % , had Web access from home , and could use a computer with English language –based programs . Intervention patients received 12 months of Web-based care management . The Web-based program included patient access to electronic medical records , secure e-mail with providers , feedback on blood glucose readings , an educational Web site , and an interactive online diary for entering information about exercise , diet , and medication . The primary outcome was change in GHb . RESULTS —GHb levels declined by 0.7 % ( 95 % CI 0.2−1.3 ) on average among intervention patients compared with usual-care patients . Systolic blood pressure , diastolic blood pressure , total cholesterol levels , and use of in-person health care services did not differ between the two groups . CONCLUSIONS —Care management delivered through secure patient Web communications improved glycemic control in type 2 diabetes BACKGROUND Since many successful dieters regain the weight they lose , programs that teach maintenance skills are needed . We developed a maintenance program based on self-regulation theory and tested the efficacy of delivering the program face to face or over the Internet . METHODS We r and omly assigned 314 participants who had lost a mean of 19.3 kg of body weight in the previous 2 years to one of three groups : a control group , which received quarterly newsletters ( 105 participants ) , a group that received face-to-face intervention ( 105 ) , and a group that received Internet-based intervention ( 104 ) . The content of the programs in the two intervention groups was the same , emphasizing daily self-weighing and self-regulation , as was the frequency of contact with the groups . The primary outcome was weight gain over a period of 18 months . RESULTS The mean ( + /-SD ) weight gain was 2.5+/-6.7 kg in the face-to-face group , 4.7+/-8.6 kg in the Internet group , and 4.9+/-6.5 kg in the control group , with a significant difference between the face-to-face group and the control group ( 2.4 kg ; 95 % confidence interval [ CI ] , 0.002 to 10.8 ; P=0.05 ) . The proportion of participants who regained 2.3 kg or more over the 18-month period was significantly higher in the control group ( 72.4 % ) than in the face-to-face group ( 45.7 % ; absolute difference , 27 % ; 95 % CI , 14 to 39 ; P<0.001 ) or the Internet group ( 54.8 % ; absolute difference , 18 % ; 95 % CI , 5 to 30 ; P=0.008 ) . Daily self-weighing increased in both intervention groups and was associated with a decreased risk of regaining 2.3 kg or more ( P<0.001 ) . CONCLUSIONS As compared with receiving quarterly newsletters , a self-regulation program based on daily weighing improved maintenance of weight loss , particularly when delivered face to face . ( Clinical Trials.gov number , NCT00067145 [ Clinical Trials.gov ] . Objective To estimate the percentage reduction in incidence of dementia that would be obtained if specific risk factors were eliminated . Design Prospect i ve seven year cohort study . Setting General population , Montpellier , France . Participants 1433 people aged over 65 with a mean baseline age of 72.5 ( SD 5.1 ) years . Main outcome measures Diagnosis of mild cognitive impairment or dementia established by a st and ardised neurological examination . Results Cox models were constructed to derive hazard ratios and determine confounding and interaction effects for potentially modifiable risk factors for dementia . Mean percentage population attributable fractions were calculated with 95 % confidence intervals derived from bootstrapping for seven year incidence of mild cognitive impairment or dementia . The final model retained crystallised intelligence ( population attributable fraction 18.11 % , 95 % confidence interval 10.91 % to 25.42 % ) , depression ( 10.31 % , 3.66 % to 17.17 % ) , fruit and vegetable consumption ( 6.46 % , 0.15 % to 13.06 % ) , diabetes ( 4.88 % , 1.87 % to 7.98 % ) , and apolipoprotein E ε4 allele ( 7.11 % , 2.44 % to 11.98 % ) . Conclusions Increasing crystallised intelligence and fruit and vegetable consumption and eliminating depression and diabetes are likely to have the biggest impact on reducing the incidence of dementia , outweighing even the effect of removing the principal known genetic risk factor . Although causal relations can not be concluded with certainty , the study suggests priorities that may inform public health programmes Background Using the Internet may prove useful in providing nutrition counselling and social support for patients with chronic diseases . Objective We evaluated the impact of Web-based nutrition counselling and social support on social support measures , anthropometry , blood pressure , and serum cholesterol in patients at increased cardiovascular risk . Methods We conducted a r and omized controlled trial among patients with increased cardiovascular risk in Canadian family practice s. During 8 months , patients in the intervention group and control groups received usual care . Patients in the intervention group also had access to a Web-based nutrition counselling and social support tool ( Heartweb ) . Site use during the study was monitored . We measured social support , body mass index , waist/hip ratio , blood pressure , and cholesterol levels at baseline and at 4 and 8 months to assess the effectiveness of the intervention . Results We r and omized 146 patients into the Web-based intervention ( n=73 ) or the control group ( n=73 ) . Within the Web-based intervention group , Heartweb was used by only 33 % ( 24/73 ) of patients , with users being significantly younger than nonusers ( P=.03 ) . There were no statistically significant differences between the intervention group and the control group in changes in social support , anthropometry , blood pressure , and serum cholesterol levels . Conclusions Uptake of the Web-based intervention was low . This study showed no favourable effects of a Web-based nutrition counselling and social support intervention on social support , anthropometry , blood pressure , and serum cholesterol . Improvements in reach and frequency of site use are needed to increase the effectiveness of Web-based interventions BACKGROUND We evaluated an Internet- and telephone-based telemedicine system for reducing blood pressure ( BP ) in underserved subjects with hypertension . METHODS A total of 241 patients with systolic BP ≥140 mm Hg were r and omized to usual care ( C ; n = 121 ) or telemedicine ( T ; n = 120 ) . The T group reported BP , heart rate , weight , steps/day , and tobacco use twice weekly . The primary outcome was BP control at 6 months . RESULTS Average age was 59.6 years , average body mass index was 33.7 kg/m(2 ) , 79 % were female , 81 % were African American , 15 % were white , 53 % were at or below the federal poverty level , 18 % were smokers , and 32 % had diabetes . Six-month follow-up was achieved in 206 subjects ( C : 107 , T : 99 ) . Goal BP was achieved in 52.3 % in C and 54.5 % in T ( P = .43 ) . Systolic BP change ( C : -13.9 mm Hg , T : -18.2 ; P = .118 ) was similar in both groups . Subjects in the T group reported BP 7.7 ± 6.9 d/mo . Results were not affected by age , sex , ethnicity , education , or income . In nondiabetic T subjects , goal BP was achieved in 58.2 % compared with 45.2 % of diabetic T subjects ( P = .024 ) . Nondiabetic T subjects demonstrated a greater reduction in systolic BP ( T : -19 ± 20 mm Hg , C : -12 ± 19 mm Hg ; P = .037 ) . No difference in BP response between C and T was noted in patients with diabetes . CONCLUSION In hypertensive subjects , engagement in a system of care with or without telemedicine result ed in significant BP reduction . Telemedicine for nondiabetic patients result ed in a greater reduction in systolic BP compared with usual care . Telemedicine may be a useful tool for managing hypertension particularly among nondiabetic subjects BACKGROUND The Diabetes Prevention Program ( DPP ) lifestyle intervention reduced the incidence of type 2 diabetes mellitus ( DM ) among high-risk adults by 58 % , with weight loss as the dominant predictor . However , it has not been adequately translated into primary care . METHODS We evaluated 2 adapted DPP lifestyle interventions among overweight or obese adults who were recruited from 1 primary care clinic and had pre-DM and /or metabolic syndrome . Participants were r and omized to ( 1 ) a coach-led group intervention ( n = 79 ) , ( 2 ) a self-directed DVD intervention ( n = 81 ) , or ( 3 ) usual care ( n = 81 ) . During a 3-month intensive intervention phase , the DPP-based behavioral weight-loss curriculum was delivered by lifestyle coach-led small groups or home-based DVD . During the maintenance phase , participants in both interventions received lifestyle change coaching and support remotely-through secure email within an electronic health record system and the American Heart Association Heart360 website for weight and physical activity goal setting and self-monitoring . The primary outcome was change in body mass index ( BMI ) ( calculated as weight in kilograms divided by height in meters squared ) from baseline to 15 months . RESULTS At baseline , participants had a mean ( SD ) age of 52.9 ( 10.6 ) years and a mean BMI of 32.0 ( 5.4 ) ; 47 % were female ; 78 % , non-Hispanic white ; and 17 % , Asian/Pacific Isl and er . At month 15 , the mean ± SE change in BMI from baseline was -2.2 ± 0.3 in the coach-led group vs -0.9 ± 0.3 in the usual care group ( P < .001 ) and -1.6 ± 0.3 in the self-directed group vs usual care ( P = .02 ) . The percentages of participants who achieved the 7 % DPP-based weight-loss goal were 37.0 % ( P = .003 ) and 35.9 % ( P = .004 ) in the coach-led and self-directed groups , respectively , vs 14.4 % in the usual care group . Both interventions also achieved greater net improvements in waist circumference and fasting plasma glucose level . CONCLUSION Proven effective in a primary care setting , the 2 DPP-based lifestyle interventions are readily scalable and exportable with potential for substantial clinical and public health impact . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00842426 Aim . To compare the effectiveness of antihypertensive treatment based on telemonitoring of home blood pressure ( BP ) and conventional monitoring of office BP . Methods . Hypertensive patients ( n = 236 ) participated in a r and omized , controlled study . In the intervention group , antihypertensive treatment was based on home BP monitoring . BP readings were registered by a PDA and automatically transmitted to a server , by which the patient and doctor could communicate . In the control group , patients received usual care with office visits to adjust antihypertensive treatment as needed . Primary outcome was difference in systolic daytime ambulatory BP monitoring ( ABPM ) change between baseline and 6 months . Results . In both groups , systolic daytime ABPM decreased significantly from baseline to follow‐up . The decrease in systolic daytime ABPM was −11.9 mmHg in the intervention group and −9.6 mmHg in the control group ( mean difference −2.3 [ 95 % CI −6.1 to −1.5 ] , p = 0.225 ) . The likelihood of daytime ABPM normalization was similar in the two groups [ 32/113 ( 28 % ) vs 46/123 ( 37 % ) , p = 0.139 ] . Conclusion . Antihypertensive treatment based on telemonitoring of home BP was as effective as usual monitoring of office BP with regards to reduction of BP . Trial registration : Clinical Trials.gov identifier : NCT00282334 Background —To determine whether a pharmacist-led , Heart360-enabled , home blood pressure monitoring ( HBPM ) intervention improves blood pressure ( BP ) control compared with usual care ( UC ) . Methods and Results —This r and omized , controlled trial was conducted in 10 Kaiser Permanente Colorado clinics . Overall , 348 patients with BP above recommended levels were r and omized to the HBPM ( n=175 ) or UC ( n=173 ) groups . There were no statistically significant differences in baseline characteristics between the groups ; however , there was a trend toward a higher baseline BP for the HBPM group compared with the UC group ( 148.8 versus 145.5 mm Hg for systolic BP ; 89.6 versus 88.0 mm Hg for diastolic BP ) . At 6 months , the proportion of patients achieving BP goal was significantly higher in the HBPM group ( 54.1 % ) than in the UC group ( 35.4 % ; P<0.001 ) . Compared with the UC group , the HBPM group experienced a −12.4-mm Hg larger ( 95 % confidence interval , −16.3 to −8.6 ) reduction in systolic BP and a −5.7-mm Hg larger ( 95 % confidence interval , −7.8 to −3.6 ) reduction in diastolic BP . The impact of the intervention on BP reduction was even larger for the subgroup of patients with diabetes mellitus or chronic kidney disease . The HBPM group had more e-mail and telephone contacts and greater medication regimen intensification . The proportion of patients reporting high satisfaction with hypertension care was significantly greater in the HBPM group ( 58 % ) than in the UC group ( 42 % ) , P<0.001 . Conclusions —A pharmacist-led , Heart360-supported , home BP monitoring intervention led to greater BP reductions , superior BP control , and higher patient satisfaction than UC . Clinical Trial Registration —URL : http://www . clinical trials.gov/ct2/show/NCT01162759 . Unique identifier : NCT01162759 Background It is possible to provide patients with secure access to their medical records using the Internet . Such access may assist patients in the self-management of chronic diseases such as heart failure . Objective To assess how a patient-accessible online medical record affects patient care and clinic operations . The SPPARO ( System Providing Access to Records Online ) software consisted of a web-based electronic medical record , an educational guide , and a messaging system enabling electronic communication between the patient and staff . Methods A r and omized controlled trial was conducted in a specialty practice for patients with heart failure . Surveys assessing doctor-patient communication , adherence , and health status were conducted at baseline , 6 months , and 1 year . Use of the system , message volume , utilization of clinical services , and mortality were monitored . Results One hundred and seven patients were enrolled ( 54 intervention and 53 controls ) . At 12 months , the intervention group was not found to be superior in self-efficacy ( KCCQ self-efficacy score 91 vs. 85 , p=0.08 ) , but was superior in general adherence ( MOS compliance score 85 vs. 78 , p=0.01 ) . A trend was observed for better satisfaction with doctor-patient communication . The intervention group had more emergency department visits ( 20 vs. 8 , p=0.03 ) , but these visits were not temporally related to use of the online medical record . There were no adverse effects from use of the system . Conclusions Providing patients with congestive heart failure access to an online medical record was feasible and improved adherence . An effect on health status could not be demonstrated in this pilot study OBJECTIVE To compare three interventions to reduce diabetes distress ( DD ) and improve self-management among non– clinical ly depressed adults with type 2 diabetes mellitus ( T2DM ) . RESEARCH DESIGN AND METHODS In REDEEM , 392 adults with T2DM and DD were r and omized to computer-assisted self-management ( CASM ) , CASM plus DD-specific problem solving ( CAPS ) , or a computer-administered minimal supportive intervention . Primary outcomes were Diabetes Distress Scale ( DDS ) total , the Emotional Burden ( EB ) and Regimen Distress ( RD ) DDS subscales , and diet , exercise , and medication adherence . RESULTS Significant and clinical ly meaningful reductions in DD ( DDS , EB , and RD ) and self-management behaviors occurred in all three conditions ( P < 0.001 ) , with no significant between-group differences . There was , however , a significant group × baseline distress interaction ( P < 0.02 ) , in which patients with high baseline RD in the CAPS condition displayed significantly larger RD reductions than those in the other two conditions . RD generated the most distress and displayed the greatest distress reduction as a result of intervention . The pace of DD reduction varied by patient age : older patients demonstrated significant reductions in DD early in the intervention , whereas younger adults displayed similar reductions later . Reductions in DD were accompanied by significant improvements in healthy eating , physical activity , and medication adherence , although not by change in HbA1c . CONCLUSIONS DD is malleable and highly responsive to intervention . Interventions that enhance self-management also reduce DD significantly , but DD-specific interventions may be necessary for patients with high initial levels of DD . Future research should identify the minimal , most cost-effective interventions to reduce DD and improve self-management OBJECTIVE To evaluate an online disease management system supporting patients with uncontrolled type 2 diabetes . MATERIAL S AND METHODS Engaging and Motivating Patients Online With Enhanced Re sources for Diabetes was a 12-month parallel r and omized controlled trial of 415 patients with type 2 diabetes with baseline glycosylated hemoglobin ( A1C ) values ≥7.5 % from primary care sites sharing an electronic health record . The intervention included : ( 1 ) wirelessly uploaded home glucometer readings with graphical feedback ; ( 2 ) comprehensive patient-specific diabetes summary status report ; ( 3 ) nutrition and exercise logs ; ( 4 ) insulin record ; ( 5 ) online messaging with the patient 's health team ; ( 6 ) nurse care manager and dietitian providing advice and medication management ; and ( 7 ) personalized text and video educational ' nuggets ' dispensed electronically by the care team . A1C was the primary outcome variable . RESULTS Compared with usual care ( UC , n=189 ) , patients in the intervention ( INT , n=193 ) group had significantly reduced A1C at 6 months ( -1.32 % INT vs -0.66 % UC ; p<0.001 ) . At 12 months , the differences were not significant ( -1.14 % INT vs -0.95 % UC ; p=0.133 ) . In post hoc analysis , significantly more INT patients had improved diabetes control ( > 0.5 % reduction in A1C ) than UC patients at 12 months ( 69.9 ( 95 % CI 63.2 to 76.5 ) vs 55.4 ( 95 % CI 48.4 to 62.5 ) ; p=0.006 ) . CONCLUSIONS A nurse-led , multidisciplinary health team can manage a population of diabetic patients in an online disease management program . INT patients achieved greater decreases in A1C at 6 months than UC patients , but the differences were not sustained at 12 months . More INT than UC patients achieved improvement in A1C ( > 0.5 % decrease ) . Trial registered in clinical trials.gov : # NCT00542204 BACKGROUND Whether the treatment of patients with hypertension who are 80 years of age or older is beneficial is unclear . It has been suggested that antihypertensive therapy may reduce the risk of stroke , despite possibly increasing the risk of death . METHODS We r and omly assigned 3845 patients from Europe , China , Australasia , and Tunisia who were 80 years of age or older and had a sustained systolic blood pressure of 160 mm Hg or more to receive either the diuretic indapamide ( sustained release , 1.5 mg ) or matching placebo . The angiotensin-converting-enzyme inhibitor perindopril ( 2 or 4 mg ) , or matching placebo , was added if necessary to achieve the target blood pressure of 150/80 mm Hg . The primary end point was fatal or nonfatal stroke . RESULTS The active-treatment group ( 1933 patients ) and the placebo group ( 1912 patients ) were well matched ( mean age , 83.6 years ; mean blood pressure while sitting , 173.0/90.8 mm Hg ) ; 11.8 % had a history of cardiovascular disease . Median follow-up was 1.8 years . At 2 years , the mean blood pressure while sitting was 15.0/6.1 mm Hg lower in the active-treatment group than in the placebo group . In an intention-to-treat analysis , active treatment was associated with a 30 % reduction in the rate of fatal or nonfatal stroke ( 95 % confidence interval [ CI ] , -1 to 51 ; P=0.06 ) , a 39 % reduction in the rate of death from stroke ( 95 % CI , 1 to 62 ; P=0.05 ) , a 21 % reduction in the rate of death from any cause ( 95 % CI , 4 to 35 ; P=0.02 ) , a 23 % reduction in the rate of death from cardiovascular causes ( 95 % CI , -1 to 40 ; P=0.06 ) , and a 64 % reduction in the rate of heart failure ( 95 % CI , 42 to 78 ; P<0.001 ) . Fewer serious adverse events were reported in the active-treatment group ( 358 , vs. 448 in the placebo group ; P=0.001 ) . CONCLUSIONS The results provide evidence that antihypertensive treatment with indapamide ( sustained release ) , with or without perindopril , in persons 80 years of age or older is beneficial . ( Clinical Trials.gov number , NCT00122811 [ Clinical Trials.gov ] . ) OBJECTIVE The Internet is used worldwide as a communication tool . To improve the quality of diabetes control , we investigated the effectiveness of an Internet-based blood glucose monitoring system ( IBGMS ) on controlling the changes in HbA(1c ) levels . RESEARCH DESIGN AND METHODS We conducted a r and omized clinical trial involving 110 patients who visited the outpatient clinic at the Kangnam St. Mary 's Hospital for 3 months . The study subjects were treated with IBGMS for 12 weeks , and the control group received the usual outpatient management over the same period . HbA(1c ) and other laboratory tests were performed twice , once at the beginning of the study and again at the end of the study . RESULTS The test results from the beginning of the study established that there were no significant differences between the two groups with respect to age , sex , diabetes duration , BMI , blood pressure , HbA(1c ) , and other laboratory data . On follow-up examination 12 weeks later , HbA(1c ) levels were significantly decreased from 7.59 to 6.94 % within the intervention group ( P < 0.001 ) . At the end of the study , HbA(1c ) levels in the intervention group were significantly lower than in the control group after adjusting the baseline HbA(1c ) ( 6.94 vs. 7.62 % ; P < 0.001 , respectively ) . Among patients with baseline HbA(1c ) < 7.0 % , the patients in the intervention group had lower HbA(1c ) than those in the control group ( 6.38 vs. 6.99 % ; P < 0.05 ) . Among the patients with a baseline HbA(1c ) > or = 7.0 % , the difference between the two groups appeared more obvious : HbA(1c ) levels at the end of the study were 8.12 % . CONCLUSIONS This new IBGMS result ed in a significant reduction of HbA(1c ) during the study period . We propose that this IBGMS be used as a method for improving diabetes control Background This study provides insight into the long-term efficacy ( i.e. 12 month results ) of the Web-based or print-delivered tailored Active Plus intervention ( with and without environmental approach ) to promote physical activity ( PA ) among the over-fifties . Differences in effect among subgroups are studied as well . Methods Intervention groups ( i.e. print-delivered basic ( PB ; N = 439 ) , print-delivered environmental ( PE ; N = 435 ) , Web-based basic ( WB ; N = 423 ) , Web-based environmental ( WE ; N = 432 ) ) and a waiting list control group ( N = 411 ) were studied in a clustered r and omized controlled trial . Intervention participants received tailored advice three times within 4 months . Long-term effects ( 12 months after the intervention has started , i.e. 8 months after the intervention was completed ) on PA ( i.e. self-reported weekly minutes and days of sufficient PA ) were tested using multilevel linear regression analyses . Participants ’ age , gender , BMI , educational level , PA intention and the presence of a chronic physical limitation were considered to be potential moderators of the effect . Results Overall , the Active Plus intervention was effective in increasing weekly days of sufficient PA ( B=0.49 ; p=.005 ) , but ineffective in increasing weekly minutes of PA ( B=84.59 ; p=.071 ) . Per intervention condition analysis showed that the PB-intervention ( Bdays=0.64 ; p=.002 ; Bmi n=111.36 ; p=.017 ) and the PE-intervention ( Bdays=0.70 ; p=.001 ; Bmi n=157.41 ; p=.001 ) were effective in increasing days and minutes of PA . Neither Web-based conditions significantly increased PA , while the control group decreased their PA . In contrast to the intervention effect on minutes of PA , the effect on weekly days of PA was significantly moderated by the participants ’ baseline intention to be sufficiently physically active . Conclusions In general , after 12 months the print-delivered interventions result ed in stronger effects than the Web-based interventions . The participants ’ baseline intention was the only significant moderator of the intervention effect . All other assessed user characteristics did not significantly moderate the effect of the intervention , which might indicate that the intervention is sufficiently tailored to the different participant characteristics . Additional efforts should be taken to increase the sustainability of Web-based interventions .Trial registration Dutch Trial Register : NTR2297 CONTEXT Telemedicine is a promising but largely unproven technology for providing case management services to patients with chronic conditions and lower access to care . OBJECTIVES To examine the effectiveness of a telemedicine intervention to achieve clinical management goals in older , ethnically diverse , medically underserved patients with diabetes . DESIGN , Setting , and Patients A r and omized controlled trial was conducted , comparing telemedicine case management to usual care , with blinded outcome evaluation , in 1,665 Medicare recipients with diabetes , aged > /= 55 years , residing in federally design ated medically underserved areas of New York State . Interventions Home telemedicine unit with nurse case management versus usual care . Main Outcome Measures The primary endpoints assessed over 5 years of follow-up were hemoglobin A1c ( HgbA1c ) , low density lipoprotein ( LDL ) cholesterol , and blood pressure levels . RESULTS Intention-to-treat mixed models showed that telemedicine achieved net overall reductions over five years of follow-up in the primary endpoints ( HgbA1c , p = 0.001 ; LDL , p < 0.001 ; systolic and diastolic blood pressure , p = 0.024 ; p < 0.001 ) . Estimated differences ( 95 % CI ) in year 5 were 0.29 ( 0.12 , 0.46)% for HgbA1c , 3.84 ( -0.08 , 7.77 ) mg/dL for LDL cholesterol , and 4.32 ( 1.93 , 6.72 ) mm Hg for systolic and 2.64 ( 1.53 , 3.74 ) mm Hg for diastolic blood pressure . There were 176 deaths in the intervention group and 169 in the usual care group ( hazard ratio 1.01 [ 0.82 , 1.24 ] ) . CONCLUSIONS Telemedicine case management result ed in net improvements in HgbA1c , LDL-cholesterol and blood pressure levels over 5 years in medically underserved Medicare beneficiaries . Mortality was not different between the groups , although power was limited . Trial Registration http:// clinical trials.gov Identifier : NCT00271739 BACKGROUND Observational epidemiological studies have shown a positive association between hypertension and risk of incident dementia ; however , the effects of antihypertensive therapy on cognitive function in controlled trials have been conflicting , and meta-analyses of the trials have not provided clear evidence of whether antihypertensive treatment reduces dementia incidence . The Hypertension in the Very Elderly trial ( HYVET ) was design ed to assess the risks and benefits of treatment of hypertension in elderly patients and included an assessment of cognitive function . METHODS Patients with hypertension ( systolic pressure 160 - 200 mm Hg ; diastolic pressure < 110 mm Hg ) who were aged 80 years or older were enrolled in this double-blind , placebo-controlled trial . Participants were r and omly assigned to receive 1.5 mg slow release indapamide , with the option of 2 - 4 mg perindopril , or placebo . The target systolic blood pressure was 150 mm Hg ; the target diastolic blood pressure was 80 mm Hg . Participants had no clinical diagnosis of dementia at baseline , and cognitive function was assessed at baseline and annually with the mini-mental state examination ( MMSE ) . Possible cases of incident dementia ( a fall in the MMSE score to < 24 points or a drop of three points in 1 year ) were assessed by st and ard diagnostic criteria and expert review . The trial was stopped in 2007 at the second interim analysis after treatment result ed in a reduction in stroke and total mortality . Analysis was by intention to treat . The trial is registered with Clinical Trials.gov , number NCT00122811 . FINDINGS 3336 HYVET participants had at least one follow-up assessment ( mean 2.2 years ) and were included : 1687 participants were r and omly assigned to the treatment group and 1649 to the placebo group . Only five reports of adverse effects were attributed to the medication : three in the placebo group and two in the treatment group . The mean decrease in systolic blood pressure between the treatment and placebo groups at 2 years was systolic -15 mm Hg , p<0.0001 ; and diastolic -5.9 mm Hg , p<0.0001 . There were 263 incident cases of dementia . The rates of incident dementia were 38 per 1000 patient-years in the placebo group and 33 per 1000 patient-years in the treatment group . There was no significant difference between treatment and placebo groups ( hazard ratio [ HR ] 0.86 , 95 % CI 0.67 - 1.09 ) ; however , when these data were combined in a meta- analysis with other placebo-controlled trials of antihypertensive treatment , the combined risk ratio favoured treatment ( HR 0.87 , 0.76 - 1.00 , p=0.045 ) . INTERPRETATION Antihypertensive treatment in elderly patients does not statistically reduce incidence of dementia . This negative finding might have been due to the short follow-up , owing to the early termination of the trial , or the modest effect of treatment . Nevertheless , the HYVET findings , when included in a meta- analysis , might support antihypertensive treatment to reduce incident dementia BACKGROUND Control of blood pressure is a key component of cardiovascular disease prevention , but is difficult to achieve and until recently has been the sole preserve of health professionals . This study assessed whether self-management by people with poorly controlled hypertension result ed in better blood pressure control compared with usual care . METHODS This r and omised controlled trial was undertaken in 24 general practice s in the UK . Patients aged 35 - 85 years were eligible for enrolment if they had blood pressure more than 140/90 mm Hg despite antihypertensive treatment and were willing to self-manage their hypertension . Participants were r and omly assigned in a 1:1 ratio to self-management , consisting of self-monitoring of blood pressure and self-titration of antihypertensive drugs , combined with telemonitoring of home blood pressure measurements or to usual care . R and omisation was done by use of a central web-based system and was stratified by general practice with minimisation for sex , baseline systolic blood pressure , and presence or absence of diabetes or chronic kidney disease . Neither participants nor investigators were masked to group assignment . The primary endpoint was change in mean systolic blood pressure between baseline and each follow-up point ( 6 months and 12 months ) . All r and omised patients who attended follow-up visits at 6 months and 12 months and had complete data for the primary outcome were included in the analysis , without imputation for missing data . This study is registered as an International St and ard R and omised Controlled Trial , number IS RCT N17585681 . FINDINGS 527 participants were r and omly assigned to self-management ( n=263 ) or control ( n=264 ) , of whom 480 ( 91 % ; self-management , n=234 ; control , n=246 ) were included in the primary analysis . Mean systolic blood pressure decreased by 12.9 mm Hg ( 95 % CI 10.4 - 15.5 ) from baseline to 6 months in the self-management group and by 9.2 mm Hg ( 6.7 - 11.8 ) in the control group ( difference between groups 3.7 mm Hg , 0.8 - 6.6 ; p=0.013 ) . From baseline to 12 months , systolic blood pressure decreased by 17.6 mm Hg ( 14.9 - 20.3 ) in the self-management group and by 12.2 mm Hg ( 9.5 - 14.9 ) in the control group ( difference between groups 5.4 mm Hg , 2.4 - 8.5 ; p=0.0004 ) . Frequency of most side-effects did not differ between groups , apart from leg swelling ( self-management , 74 patients [ 32 % ] ; control , 55 patients [ 22 % ] ; p=0.022 ) . INTERPRETATION Self-management of hypertension in combination with telemonitoring of blood pressure measurements represents an important new addition to control of hypertension in primary care . FUNDING Department of Health Policy Research Programme , National Coordinating Centre for Research Capacity Development , and Midl and s Research Practice s Consortium BACKGROUND A prerequisite to translating research findings into practice is information on consistency of implementation , maintenance of results , and generalization of effects . This follow-up report is one of the few experimental studies to provide such information on Internet-based health education . METHODS We present follow-up data 10 months following r and omization on the " Diabetes Network ( D-Net ) " Internet-based self-management project , a r and omized trial evaluating the incremental effects of adding ( 1 ) tailored self-management training or ( 2 ) peer support components to a basic Internet-based , information-focused comparison intervention . Participants were 320 adult type 2 diabetes patients from participating primary care offices , mean age 59 ( SD = 9.2 ) , who were relatively novice Internet users . RESULTS All intervention components were consistently implemented by staff , but participant website usage decreased over time . All conditions were significantly improved from baseline on behavioral , psychosocial , and some biological outcomes ; and there were few differences between conditions . Results were robust across on-line coaches , patient characteristics , and participating clinics . CONCLUSIONS The basic D-Net intervention was implemented well and improvements were observed across a variety of patients , interventionists , and clinics . There were , however , difficulties in maintaining usage over time and additions of tailored self-management and peer support components generally did not significantly improve results OBJECTIVE —To investigate the long-term effectiveness of the Internet-based glucose monitoring system ( IBGMS ) on glucose control in patients with type 2 diabetes . RESEARCH DESIGN AND METHODS —We conducted a prospect i ve , r and omized , controlled trial in 80 patients with type 2 diabetes for 30 months . The intervention group was treated with the IBGMS , while the control group made conventional office visits only . HbA1c ( A1C ) was performed at 3-month intervals . For measuring of the stability of glucose control , the SD value of A1C levels for each subject was used as the A1C fluctuation index ( HFI ) . RESULTS —The mean A1C and HFI were significantly lower in the intervention group ( n = 40 ) than in the control group ( n = 40 ) . ( A1C [ mean ± SD ] 6.9 ± 0.9 vs. 7.5 ± 1.0 % , P = 0.009 ; HFI 0.47 ± 0.23 vs. 0.78 ± 0.51 , P = 0.001 ; intervention versus control groups , respectively ) . Patients in the intervention group with a basal A1C ≥7 % ( n = 27 ) had markedly lower A1C levels than corresponding patients in the control group during the first 3 months and maintained more stable levels throughout the study ( P = 0.022 ) . Control patients with a basal A1C < 7 % ( n = 15 ) showed the characteristic bimodal distribution of A1C levels , whereas the A1C levels in the intervention group remained stable throughout the study with low HFI . CONCLUSIONS —Long-term use of the IBGMS has proven to be superior to conventional diabetes care systems based on office visits for controlling blood glucose and achieving glucose stability This study aim ed to test the effects of providing Web-based diabetes education to individuals with type 2 diabetes on the A1c level and health check attendance . The study participants comprised 122 individuals with type 2 diabetes , who had access to the Internet , had completed their basic diabetes education , and had similar basic situational factors . Using a r and omization method , these participants were chosen from the patients being monitored by the diabetes nurses . The experimental group ( n = 61 ) was monitored via the Web . From measurements recorded in the sixth month of monitoring , we found that A1c levels of the individuals with diabetes who were monitored through the Web decreased ( t = 6.63 ; P < .05 ) , and the rate of attending health check visits increased ( z = 5.97 ; P < .05 ) , while no difference was detected in the control group ( t = −0.63 ; P = .534 ; z = −0.80 ; P = .426 ) . To maintain glycemic control , Web use could be adopted as a complementary tool for monitoring individuals with diabetes OBJECTIVES We examined the effects of 2 worksite health-promotion interventions ( compared with a health-education control ) on older workers ' healthy behaviors and health outcomes . METHODS We conducted a prospect i ve , r and omized controlled trial with 423 participants aged 40 years and older . Participants were categorized into 3 study arms : the COACH intervention combined Web-based risk assessment s with personal coaching support , the RealAge intervention used a Web-based risk assessment and behavior-specific modules , and a control group received printed health-promotion material s. Participants were assessed at baseline , 6 months , and 12 months . R and om-effects modeling controlled for baseline stage of change for all behaviors of interest in all groups . RESULTS At 6 and 12 months , COACH participants showed significantly increased fruit and vegetable consumption ( P = .026 ; P < .001 ) and participation in physical activity ( P = .05 ; P = .013 ) , and at 12 months they showed decreased percentage of energy from fat ( P = .027 ) . RealAge participants showed significantly decreased waist circumference at 6 and 12 months ( P = .05 ; P = .018 ) . CONCLUSIONS COACH participants were twice as likely to use the COACH intervention as RealAge participants were to use the RealAge intervention . COACH participants experienced twice the number of positive outcomes that control participants experienced Background : Diabetes mellitus is a complex disease with serious complications . Electronic decision support , providing information that is shared and discussed by both patient and physician , encourages timely interventions and may improve the management of this chronic disease . However , it has rarely been tested in community-based primary care . Methods : In this pragmatic r and omized trial , we r and omly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care . The intervention involved shared access by the primary care provider and the patient to a Web-based , colour-coded diabetes tracker , which provided sequential monitoring values for 13 diabetes risk factors , their respective targets and brief , prioritized messages of advice . The primary outcome measure was a process composite score . Secondary outcomes included clinical composite scores , quality of life , continuity of care and usability . The outcome assessors were blinded to each patient ’s intervention status . Results : We recruited sequentially 46 primary care providers and then 511 of their patients ( mean age 60.7 [ st and ard deviation 12.5 ] years ) . Mean follow-up was 5.9 months . The process composite score was significantly better for patients in the intervention group than for control patients ( difference 1.27 , 95 % confidence interval [ CI ] 0.79–1.75 , p < 0.001 ) ; 61.7 % ( 156/253 ) of patients in the intervention group , compared with 42.6 % ( 110/258 ) of control patients , showed improvement ( difference 19.1 % , p < 0.001 ) . The clinical composite score also had significantly more variables with improvement for the intervention group ( 0.59 , 95 % CI 0.09–1.10 , p = 0.02 ) , including significantly greater declines in blood pressure ( −3.95 mm Hg systolic and −2.38 mm Hg diastolic ) and glycated hemoglobin ( −0.2 % ) . Patients in the intervention group reported greater satisfaction with their diabetes care . Interpretation : A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care . ( Clinical Trials.gov trial register no. NCT00813085 . BACKGROUND The emergence of the World Wide Web in the last decade has made it feasible for the Internet to be a vehicle for chronic disease management . METHODS A r and omized controlled trial ( n = 62 ) testing the effects of a 6-month web-based intervention plus usual care , compared with usual care alone , among adults 60 years of age and older with diabetes . The outcomes were hemoglobin A1c ( HbA1c ) , blood pressure , weight , cholesterol , and high-density lipoprotein ( HDL ) levels . RESULTS A multivariate analysis of covariance controlling for all baseline outcome variables , age , gender , and number of years with diabetes showed significant ( P = 0.001 ) reductions in HbA1c , weight , and cholesterol level and significant improvement in HDL levels in the intervention versus the control group . CONCLUSIONS Findings show a web-based intervention was effective in improving HbA1c , weight , cholesterol , and HDL levels at a 6-month follow-up . Future research is needed to investigate the long-term effectiveness of web-based interventions OBJECTIVES The aim of this study is to evaluate methods for lowering cardiovascular disease ( CVD ) risk in asymptomatic urban and rural underserved subjects . BACKGROUND Medically underserved population s are at increased CVD risk , and systems to lower CVD risk are needed . Nurse management ( NM ) and telemedicine ( T ) systems may provide low-cost solutions for this care . METHODS We r and omized 465 subjects without overt CVD , with Framingham CVD risk > 10 % to NM with 4 visits over 1 year , or NM plus T to facilitate weight , blood pressure ( BP ) , and physical activity reporting . The study goal was to reduce CVD risk by 5 % . RESULTS Three hundred eighty-eight subjects completed the study . Cardiovascular disease risk fell by ≥ 5 % in 32 % of the NM group and 26 % of the T group ( P , nonsignificant ) . In hyperlipidemic subjects , total cholesterol decreased ( NM -21.9 ± 39.4 , T -22.7 ± 41.3 mg/dL ) significantly . In subjects with grade II hypertension ( systolic BP ≥ 160 mm Hg , 24 % of subjects ) , both NM and T groups had a similar BP response ( average study BP : NM 147.4 ± 17.5 , T 145.3 . ± 18.4 , P is nonsignificant ) , and for those with grade I hypertension ( 37 % of subjects ) , T had a lower average study BP compared to NM ( NM 140.4 ± 16.9 , T 134.6 ± 15.0 , P = .058 ) . In subjects at high risk ( Framingham score ≥ 20 % ) , risk fell 6.0 % ± 9.9 % ; in subjects at intermediate risk ( Framingham score ≥ 10 , < 20 ) , risk fell 1.3 % ± 4.5 % ( P < .001 compared to high-risk subjects ) . Medication adherence was similar in both high- and intermediate-risk subjects . CONCLUSIONS In 2 underserved population s , CVD risk was reduced by a nurse intervention ; T did not add to the risk improvement . Reductions in BP and blood lipids occurred in both high- and intermediate-risk subjects with greatest reductions noted in the high-risk subjects . Frequent communication using a nurse intervention contributes to improved CVD risk in asymptomatic , underserved subjects with increased CVD risk . Telemedicine did not change the effectiveness of the nurse intervention OBJECTIVE This study examined the effectiveness of a fully automated web-based programme to increase physical activity in adults with Type 2 diabetes . METHODS Between May and July 2010 , participants were r and omly allocated into either a 12-week intervention ( n=195 ) or a control ( n=202 ) group . Participants were adults diagnosed with Type 2 diabetes , residing in Australia . Participants were assessed at baseline , 12 and 36weeks . The primary physical activity outcome was self-reported minutes of total physical activity . Secondary physical activity outcomes included minutes spent walking , and engaged in moderate , and vigorous physical activity . Additional measures included website satisfaction and website usage . The intervention consisted of a 12-week web-based physical activity intervention developed based on the Theory of Planned Behavior and self-management framework . Data were analysed from 2011 to 2012 . RESULTS There was a significant group-by-time interaction ( X(2 ) (df=1)=6.37 , p<.05 ) for total physical activity favouring the intervention group d=0.11 , for those who completed the intervention , however this was not significant in the intention-to-treat analysis d=0.01 . The intervention yielded high website satisfaction and usage . CONCLUSIONS In general , there is some evidence for the effectiveness of web-based interventions for improving physical activity levels ; however it is clear that maintaining improvements remains an issue BACKGROUND Obesity and its cardiovascular complications are extremely common medical problems , but evidence on how to accomplish weight loss in clinical practice is sparse . METHODS We conducted a r and omized , controlled trial to examine the effects of two behavioral weight-loss interventions in 415 obese patients with at least one cardiovascular risk factor . Participants were recruited from six primary care practice s ; 63.6 % were women , 41.0 % were black , and the mean age was 54.0 years . One intervention provided patients with weight-loss support remotely -- through the telephone , a study -specific Web site , and e-mail . The other intervention provided in-person support during group and individual sessions , along with the three remote means of support . There was also a control group in which weight loss was self-directed . Outcomes were compared between each intervention group and the control group and between the two intervention groups . For both interventions , primary care providers reinforced participation at routinely scheduled visits . The trial duration was 24 months . RESULTS At baseline , the mean body-mass index ( the weight in kilograms divided by the square of the height in meters ) for all participants was 36.6 , and the mean weight was 103.8 kg . At 24 months , the mean change in weight from baseline was -0.8 kg in the control group , -4.6 kg in the group receiving remote support only ( P<0.001 for the comparison with the control group ) , and -5.1 kg in the group receiving in-person support ( P<0.001 for the comparison with the control group ) . The percentage of participants who lost 5 % or more of their initial weight was 18.8 % in the control group , 38.2 % in the group receiving remote support only , and 41.4 % in the group receiving in-person support . The change in weight from baseline did not differ significantly between the two intervention groups . CONCLUSIONS In two behavioral interventions , one delivered with in-person support and the other delivered remotely , without face-to-face contact between participants and weight-loss coaches , obese patients achieved and sustained clinical ly significant weight loss over a period of 24 months . ( Funded by the National Heart , Lung , and Blood Institute and others ; Clinical Trials.gov number , NCT00783315 . ) AIMS Care management may improve the quality of diabetes care by enhancing contact between high-risk patients and their providers . This prospect i ve , longitudinal , r and omized trial sought to investigate whether telephone or online care management improves diabetes-related outcomes over time compared with usual care supplemented with Internet access and training . SUBJECTS AND METHODS One hundred fifty-one adult subjects with type 2 diabetes mellitus and an elevated hemoglobin A1c ( A1c ) level ( ≥8.5 % ) were r and omly assigned to online care management ( n=51 ) , telephone-based care management ( n=51 ) , or Web training ( n=49 ) groups . Online and telephone participants interacted with a care manager through a diabetes education and care management Web site and by telephone , respectively . The Web training group was provided with online diabetes self-management re sources but no care management support . The primary outcome measure was A1c measured every 3 months for a year . RESULTS A1c declined significantly and substantially in all groups over 12 months . A1c declined linearly at a rate of 0.32 % ( P<0.0001 ) per quarter for the online group , 0.36 % ( P<0.0001 ) for the telephone group , and 0.41 % for the Web training group ( P<0.0001 ) . The rate of change over time did not differ significantly among groups . The groups converged at 12 months with average absolute A1c difference of -1.5 % . The number of interactions with care providers was not significantly associated with the change in A1c . Blood pressure , weight , lipid levels , and diabetes distress did not differ among groups over time . CONCLUSIONS Online , telephone-based care management , and Web training for diabetes patients with elevated A1c were each associated with a substantial improvement in A1c over a 1-year period . Internet access and training alone may be as effective as care management in patients with poorly controlled diabetes Background : Online social networks ( OSNs ) are a new , promising approach for catalyzing health-related behavior change . To date , the empirical evidence on their impact has been limited . Purpose : Using a r and omized trial , we assessed the impact of a health-oriented OSN with accelerometer and scales on participant ’s physical activity , weight , and clinical indicators . Methods : A sample of 349 PeaceHealth Oregon employees and family members were r and omized to the iWell OSN or a control group and followed for 6 months in 2010 - 2011 . The iWell OSN enabled participants to connect with “ friends , ” make public postings , view contacts ’ postings , set goals , download the number of their steps from an accelerometer and their weight from a scale , view trends in physical activity and weight , and compete against others in physical activity . Both control and intervention participants received traditional education material on diet and physical activity . Laboratory data on weight and clinical indicators ( triglycerides , high-density lipoprotein , or low-density lipoprotein ) , and self-reported data on physical activity , were collected at baseline , 3 months , and 6 months . Results : At 6 months , the intervention group increased leisure walking minutes by 164 % compared with 47 % in the control group . The intervention group also lost more weight than the controls ( 5.2 pounds compared with 1.5 pounds ) . There were no observed significant differences in vigorous exercise or clinical indicators between the 2 groups . Among intervention participants , greater OSN use , as measured by number of private messages sent , was associated with a greater increase in leisure walking and greater weight reduction over the study period . Conclusions : The study provides evidence that interventions using OSNs can successfully promote increases in physical activity and weight loss BACKGROUND Web-based personal health records ( PHRs ) have been advocated as a means to improve type 2 diabetes mellitus ( DM ) care . However , few Web-based systems are linked directly to the electronic medical record ( EMR ) used by physicians . METHODS We r and omized 11 primary care practice s. Intervention practice s received access to a DM-specific PHR that imported clinical and medications data , provided patient-tailored decision support , and enabled the patient to author a " Diabetes Care Plan " for electronic su bmi ssion to their physician prior to upcoming appointments . Active control practice s received a PHR to up date and su bmi t family history and health maintenance information . All patients attending these practice s were encouraged to sign up for online access . RESULTS We enrolled 244 patients with DM ( 37 % of the eligible population with registered online access , 4 % of the overall population of patients with DM ) . Study participants were younger ( mean age , 56.1 years vs 60.3 years ; P < .001 ) and lived in higher-income neighborhoods ( median income , $ 53,784 vs $ 49,713 ; P < .001 ) but had similar baseline glycemic control compared with non participants . More patients in the intervention arm had their DM treatment regimens adjusted ( 53 % vs 15 % ; P < .001 ) compared with active controls . However , there were no significant differences in risk factor control between study arms after 1 year ( P = .53 ) . CONCLUSIONS Previsit use of online PHR linked to the EMR increased rates of DM-related medication adjustment . Low rates of online patient account registration and good baseline control among participants limited the intervention 's impact on overall risk factor control . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00251875 OBJECTIVE To evaluate the use of a local neighborhood environment-focused physical activity website and its effects on walking and overall physical activity in middle-aged adults . METHOD One-hundred and six ( 72 % women ) inactive adults aged 52+/-4.6 years were r and omly allocated to receive access to a neighborhood environment-focused website , ( Neighborhood group , n=52 ) or a motivational-information website ( Comparison group n=54 ) . Participants also received eleven emails over the 26 weeks . Study outcomes were objective ly-monitored website use , and self-reported total walking ( min/wk ) , total physical activity ( min/wk ) and neighborhood walking ( min/wk ) collected at baseline , 12 and 26 weeks . The study was conducted between August 2005 and February 2006 in Brisbane , Australia . RESULTS Website use was significantly greater among Neighborhood participants ( p=0.01 ) . Statistically significant increases in walking and total physical activity were observed in both groups . There was also a statistically significant interaction effect for total physical activity , with Neighborhood group participants maintaining more of their initial increase in physical activity at week-26 ( p<0.05 ) . Further , those in the Neighborhood group who used the website more often reported significantly more walking along the community trail at week-26 ( p=0.05 ) compared with those who did not . CONCLUSIONS A local neighborhood-environment focused physical activity website was more effective at engaging participants than a motivational-information website . Moreover , its use result ed in meaningful increases in physical activity relative to the comparison website Background — Although preventive drug therapy is a priority after acute coronary syndrome , less is known about adherence to behavioral recommendations . The aim of this study was to examine the influence of adherence to behavioral recommendations in the short term on risk of cardiovascular events . Methods and Results — The study population included 18 809 patients from 41 countries enrolled in the Organization to Assess Strategies in Acute Ischemic Syndromes ( OASIS ) 5 r and omized clinical trial . At the 30-day follow-up , patients reported adherence to diet , physical activity , and smoking cessation . Cardiovascular events ( myocardial infa rct ion , stroke , cardiovascular death ) and all-cause mortality were documented to 6 months . About one third of smokers persisted in smoking . Adherence to neither diet nor exercise recommendations was reported by 28.5 % , adherence to either diet or exercise by 41.6 % , and adherence to both by 29.9 % . In contrast , 96.1 % of subjects reported antiplatelet use , 78.9 % reported statin use , and 72.4 % reported angiotensin-converting enzyme/angiotensin receptor blocker use . Quitting smoking was associated with a decreased risk of myocardial infa rct ion compared with persistent smoking ( odds ratio , 0.57 ; 95 % confidence interval , 0.36 to 0.89 ) . Diet and exercise adherence was associated with a decreased risk of myocardial infa rct ion compared with nonadherence ( odds ratio , 0.52 ; 95 % confidence interval , 0.4 to 0.69 ) . Patients who reported persistent smoking and nonadherence to diet and exercise had a 3.8-fold ( 95 % confidence interval , 2.5 to 5.9 ) increased risk of myocardial infa rct ion/stroke/death compared with never smokers who modified diet and exercise . Conclusions — Adherence to behavioral advice ( diet , exercise , and smoking cessation ) after acute coronary syndrome was associated with a substantially lower risk of recurrent cardiovascular events . These findings suggest that behavioral modification should be given priority similar to other preventive medications immediately after acute coronary syndrome . Clinical Trial Registration Information— URL : http:// clinical trials.gov/ct2/show/NCT00139815 . Unique identifier : NCT00139815 BACKGROUND Preventive electronic (e)-counselling has been shown to reduce cardiovascular risk factors . However , heterogeneity in outcomes is commonly reported due to differences in e- protocol s. We incorporated key features of an established behavioural therapy , motivational interviewing , to help st and ardize e-counselling in order to reduce blood pressure in patients with hypertension . METHODS Subjects ( n = 387 , mean age = 56 years , 59 % female , 72 % taking ≥ 1 antihypertensive drug ) were diagnosed with stage 1 or 2 hypertension . Subjects were r and omized to a 4-month protocol of e-counselling ( beta version of the " Blood Pressure Action Plan " , Heart and Stroke Foundation of Canada ) vs waitlist control ( general e-information on heart-healthy living ) . Outcomes were systolic , diastolic , and pulse pressures , and total lipoprotein cholesterol after treatment . RESULTS Intention to treat analysis did not find a significant group difference in outcomes due to contamination across the 2 arms of this trial . However , per protocol analysis indicated that subjects receiving ≥ 8 e-counselling messages ( a priori therapeutic dose ) vs 0 e-counselling messages ( control ) demonstrated greater reduction in systolic blood pressure ( mean , -8.9 mm Hg ; 95 % confidence interval [ CI ] , -11.5 to -6.4 vs -5.0 mm Hg ; 95 % CI , -6.7 to -3.3 , P = 0.03 ) , pulse pressure ( -6.1 mm Hg ; 95 % CI , -8.1 to -4.1 vs -3.1 mm Hg ; 95 % CI , -4.3 to -1.8 , P = 0.02 ) and total cholesterol ( -0.24 mmol/L ; 95 % CI , -0.43 to -0.06 vs 0.05 mmol/L ; 95 % CI , -0.06 to 0.16 , P = 0.03 ) , but not diastolic blood pressure . CONCLUSIONS These findings support the merit of evaluating whether e-counselling can improve blood pressure control and reduce cardiovascular risk over the long-term Evidence is lacking regarding effective and sustainable weight loss approaches for use in the primary care setting . We conducted a 12-week r and omized controlled trial to evaluate the short-term efficacy of a web-based weight loss intervention among 101 primary care patients with obesity and hypertension . Patients had access to a comprehensive website that used a moderate-intensity weight loss approach design ed specifically for web-based implementation . Patients also participated in four ( two in-person and two telephonic ) counseling sessions with a health coach . Intent-to-treat analysis showed greater weight loss at 3 months ( -2.56 kg ; 95 % CI -3.60 , -1.53 ) among intervention participants ( -2.28 + /- 3.21 kg ) , relative to usual care ( 0.28 + /- 1.87 kg ) . Similar findings were observed among intervention completers ( -3.05 kg ; 95 % CI -4.24 , -1.85 ) . High rates of participant retention ( 84 % ) and website utilization were observed , with the greatest weight loss found among those with a high frequency of website logins ( quartile 4 vs. 1 : -4.16 kg ; 95 % CI -1.47 , -6.84 ) . The intervention 's approach promoted moderate weight loss at 12 weeks , though greater weight loss was observed among those with higher levels of website utilization . Efficacious web-based weight loss interventions can be successfully offered in the primary care setting CONTEXT Behavioral weight loss interventions achieve short-term success , but re-gain is common . OBJECTIVE To compare 2 weight loss maintenance interventions with a self-directed control group . DESIGN , SETTING , AND PARTICIPANTS Two-phase trial in which 1032 overweight or obese adults ( 38 % African American , 63 % women ) with hypertension , dyslipidemia , or both who had lost at least 4 kg during a 6-month weight loss program ( phase 1 ) were r and omized to a weight-loss maintenance intervention ( phase 2 ) . Enrollment at 4 academic centers occurred August 2003-July 2004 and r and omization , February-December 2004 . Data collection was completed in June 2007 . INTERVENTIONS After the phase 1 weight-loss program , participants were r and omized to one of the following groups for 30 months : monthly personal contact , unlimited access to an interactive technology-based intervention , or self-directed control . Main Outcome Changes in weight from r and omization . RESULTS Mean entry weight was 96.7 kg . During the initial 6-month program , mean weight loss was 8.5 kg . After r and omization , weight regain occurred . Participants in the personal-contact group regained less weight ( 4.0 kg ) than those in the self-directed group ( 5.5 kg ; mean difference at 30 months , -1.5 kg ; 95 % confidence interval [ CI ] , -2.4 to -0.6 kg ; P = .001 ) . At 30 months , weight regain did not differ between the interactive technology-based ( 5.2 kg ) and self-directed groups ( 5.5 kg ; mean difference -0.3 kg ; 95 % CI , -1.2 to 0.6 kg ; P = .51 ) ; however , weight regain was lower in the interactive technology-based than in the self-directed group at 18 months ( mean difference , -1.1 kg ; 95 % CI , -1.9 to -0.4 kg ; P = .003 ) and at 24 months ( mean difference , -0.9 kg ; 95 % CI , -1.7 to -0.02 kg ; P = .04 ) . At 30 months , the difference between the personal-contact and interactive technology-based group was -1.2 kg ( 95 % CI -2.1 to -0.3 ; P = .008 ) . Effects did not differ significantly by sex , race , age , and body mass index subgroups . Overall , 71 % of study participants remained below entry weight . CONCLUSIONS The majority of individuals who successfully completed an initial behavioral weight loss program maintained a weight below their initial level . Monthly brief personal contact provided modest benefit in sustaining weight loss , whereas an interactive technology-based intervention provided early but transient benefit . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00054925 BACKGROUND Few evidence -based weight loss treatment options exist for medically vulnerable patients in the primary care setting . METHODS We conducted a 2-arm , 24-month r and omized effectiveness trial in 3 Boston community health centers ( from February 1 , 2008 , through May 2 , 2011 ) . Participants were 365 obese patients receiving hypertension treatment ( 71.2 % black , 13.1 % Hispanic , 68.5 % female , and 32.9 % with less than a high school educational level ) . We r and omized participants to usual care or a behavioral intervention that promoted weight loss and hypertension self-management using eHealth components . The intervention included tailored behavior change goals , self-monitoring , and skills training , available via a website or interactive voice response ; 18 telephone counseling calls ; primary care provider endorsement ; 12 optional group support sessions ; and links with community re sources . RESULTS At 24 months , weight change in the intervention group compared with that in the usual care group was -1.03 kg ( 95 % CI , -2.03 to -0.03 kg ) . Twenty-four-month change in body mass index ( calculated as weight in kilograms divided by height in meters squared ) in the intervention group compared with that in the usual care group was -0.38 ( 95 % CI , -0.75 to -0.004 ) . Intervention participants had larger mean weight losses during the 24 months compared with that in the usual care group ( area under the receiver operating characteristic curve , -1.07 kg ; 95 % CI , -1.94 to -0.22 ) . Mean systolic blood pressure was not significantly lower in the intervention arm compared with the usual care arm . CONCLUSION The intervention produced modest weight losses , improved blood pressure control , and slowed systolic blood pressure increases in this high-risk , socioeconomically disadvantaged patient population . Trial Registration clinical trials.gov Identifier : NCT00661817 PURPOSE Despite demonstrated benefits of cardiac rehabilitation and risk factor reduction , only 11 % to 38 % of eligible patients with cardiovascular disease ( CVD ) participate in cardiac rehabilitation programs . Women and older adults are particularly less likely to participate in cardiac rehabilitation . In an effort to broaden access to cardiac rehabilitation , the authors developed an alternative Internet-based program that allows nurse case managers to provide risk factor management training , risk factor education , and monitoring services to patients with CVD . METHODS The evaluation consisted of a r and omized , clinical trial involving 104 patients with CVD , 53 of whom used the program as a special intervention ( SI ) for 6 months and 51 of whom received usual care ( UC ) . RESULTS The results indicate that fewer cardiovascular events occurred among the SI subjects ( 15.7 % ) than among the UC subjects ( 4.1 % ) ( P = .053 ) , result ing in a gross cost savings of $ 1418 US dollars per patient . With a projected program cost of $ 453 USD per patient , the return on investment is estimated at 213 % . More weight loss occurred in the SI group ( -3.68 pounds ) than in the UC group ( + .47 pounds ) ( P = .003 ) . The differences between the two groups in terms of blood pressure , lipid levels , depression scores , minutes of exercise , and dietary habits were not statistically significant . CONCLUSION An Internet-based case management system could be used as a cost-effective intervention for patients with CVD , either independently or in conjunction with traditional cardiac rehabilitation We conducted a feasibility study of a web-based intervention , which provided personalized cardiovascular disease ( CVD ) risk information , behavioural risk reduction strategies and educational re sources . Participants were block-r and omized to the 3-month intervention ( n = 47 ) or to usual care ( n = 49 ) . Participants in the intervention group were presented with their CVD risk based on the Framingham risk score , and in three subsequent online encounters could select two behavioural/lifestyle modules , giving them an opportunity to complete six modules over the course of the study . Because it was self-guided , participants had differing levels of engagement with intervention material s. Most intervention group participants ( 77 % , n = 36 ) completed all modules . After 3 months there were no significant differences between the intervention and usual care groups for systolic blood pressure , body-mass index , CVD risk , smoking cessation or medication non-adherence . The study suggests that modest clinical improvements can be achieved by interventions that are entirely web-administered . However , web-based interventions do not replace the need for human interaction to communicate CVD risk and assist with decision-making IMPORTANCE Most primary care clinicians lack the skills and re sources to offer effective lifestyle and medication ( L&M ) counseling to reduce coronary heart disease ( CHD ) risk . Thus , effective and feasible CHD prevention programs are needed for typical practice setting s. OBJECTIVE To assess the effectiveness , acceptability , and cost-effectiveness of a combined L&M intervention to reduce CHD risk offered in counselor-delivered and web-based formats . DESIGN , SETTING , AND PARTICIPANTS A comparative effectiveness trial in 5 diverse family medicine practice s in North Carolina . Participants were established patients , aged 35 to 79 years , with no known cardiovascular disease , and at moderate to high risk for CHD ( 10-year Framingham Risk Score [ FRS ] , ≥10 % ) . INTERVENTIONS Participants were r and omized to counselor-delivered or web-based format , each including 4 intensive and 3 maintenance sessions . After r and omization , both formats used a web-based decision aid showing potential CHD risk reduction associated with L&M risk-reducing strategies . Participants chose the risk-reducing strategies they wished to follow . MAIN OUTCOMES AND MEASURES The primary outcome was within-group change in FRS at 4-month follow-up . Other measures included st and ardized assessment s of blood pressure , blood lipid levels , lifestyle behaviors , and medication adherence . Acceptability and cost-effectiveness were also assessed . Outcomes were assessed at 4 and 12 months . RESULTS Of 2274 screened patients , 385 were r and omized ( 192 counselor ; 193 web ) : mean age , 62 years ; 24 % African American ; and mean FRS , 16.9 % . Follow-up at 4 and 12 months included 91 % and 87 % of the r and omized participants , respectively . There was a sustained reduction in FRS at both 4 months ( primary outcome ) and 12 months for both counselor-based ( -2.3 % [ 95 % CI , -3.0 % to -1.6 % ] and -1.9 % [ 95 % CI , -2.8 % to -1.1 % ] , respectively ) and web-based groups ( -1.5 % [ 95 % CI , -2.2 % to -0.9 % ] and -1.7 % [ 95 % CI , -2.6 % to -0.8 % ] respectively ) . At 4 months , the adjusted difference in FRS between groups was -1.0 % ( 95 % CI , -1.8 % to -0.1 % ) ( P = .03 ) , and at 12 months , it was -0.6 % ( 95 % CI , -1.7 % to 0.5 % ) ( P = .30 ) . The 12-month costs from the payer perspective were $ 207 and $ 110 per person for the counselor- and web-based interventions , respectively . CONCLUSIONS AND RELEVANCE Both intervention formats reduced CHD risk through 12-month follow-up . The web format was less expensive . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01245686 Background Approximately half of American adults do not meet recommended physical activity guidelines . Face-to-face lifestyle interventions improve health outcomes but are unlikely to yield population -level improvements because they can be difficult to disseminate , expensive to maintain , and inconvenient for the recipient . In contrast , Internet-based behavior change interventions can be disseminated widely at a lower cost . However , the impact of some Internet-mediated programs is limited by high attrition rates . Online communities that allow participants to communicate with each other by posting and reading messages may decrease participant attrition . Objective Our objective was to measure the impact of adding online community features to an Internet-mediated walking program on participant attrition and average daily step counts . Methods This r and omized controlled trial included sedentary , ambulatory adults who used email regularly and had at least 1 of the following : overweight ( body mass index [ BMI ] ≥ 25 ) , type 2 diabetes , or coronary artery disease . All participants ( n = 324 ) wore enhanced pedometers throughout the 16-week intervention and uploaded step-count data to the study server . Participants could log in to the study website to view graphs of their walking progress , individually-tailored motivational messages , and weekly calculated goals . Participants were r and omized to 1 of 2 versions of a Web-based walking program . Those r and omized to the “ online community ” arm could post and read messages with other participants while those r and omized to the “ no online community " arm could not read or post messages . The main outcome measures were participant attrition and average daily step counts over 16 weeks . Multiple regression analyses assessed the effect of the online community access controlling for age , sex , disease status , BMI , and baseline step counts . Results Both arms significantly increased their average daily steps between baseline and the end of the intervention period , but there were no significant differences in increase in step counts between arms using either intention-to-treat or completers analysis . In the intention-to-treat analysis , the average step count increase across both arms was 1888 ± 2400 steps . The percentage of completers was 13 % higher in the online community arm than the no online community arm ( online community arm , 79 % , no online community arm , 66 % , P = .02 ) . In addition , online community arm participants remained engaged in the program longer than no online community arm participants ( hazard ratio = 0.47 , 95 % CI = 0.25 - 0.90 , P = .02 ) . Participants with lower baseline social support posted more messages to the online community ( P < .001 ) and viewed more posts ( P < .001 ) than participants with higher baseline social support . Conclusion Adding online community features to an Internet-mediated walking program did not increase average daily step counts but did reduce participant attrition . Participants with low baseline social support used the online community features more than those with high baseline social support . Thus , online communities may be a promising approach to reducing attrition from online health behavior change interventions , particularly in population s with low social support . Trial Registration NCT00729040 ; http:// clinical trials.gov/ct2/show/NCT00729040 ( Archived by WebCite at http://www.webcitation.org/5v1VH3n0A Objective To determine if an intervention consisting of telemonitoring and supervision by usual primary care clinicians of home self measured blood pressure and optional patient decision support leads to clinical ly important reductions in daytime systolic and diastolic ambulatory blood pressure in patients with uncontrolled blood pressure . Design Multicentre r and omised controlled trial . Setting 20 primary care practice s in south east Scotl and . Participants 401 people aged 29 - 95 years with uncontrolled blood pressure ( mean daytime ambulatory measurement ≥135/85 mm Hg but ≤210/135 mm Hg ) . Intervention Self measurement and transmission of blood pressure readings to a secure website for review by the attending nurse or doctor and participant , with optional automated patient decision support by text or email for six months . Main outcome measures Blinded assessment of mean daytime systolic ambulatory blood pressure six months after r and omisation . Results 200 participants were r and omised to the intervention and 201 to usual care ; primary outcome data were available for 90 % of participants ( 182 and 177 , respectively ) . The mean difference in daytime systolic ambulatory blood pressure adjusted for baseline and minimisation factors between intervention and usual care was 4.3 mm Hg ( 95 % confidence interval 2.0 to 6.5 ; P=0.0002 ) and for daytime diastolic ambulatory blood pressure was 2.3 mm Hg ( 0.9 to 3.6 ; P=0.001 ) , with higher values in the usual care group . The intervention was associated with a mean increase of one general practitioner ( 95 % confidence interval 0.5 to 1.6 ; P=0.0002 ) and 0.6 ( 0.1 to 1.0 ; P=0.01 ) practice nurse consultations during the course of the study . Conclusions Supported self monitoring by telemonitoring is an effective method for achieving clinical ly important reductions in blood pressure in patients with uncontrolled hypertension in primary care setting s. However , it was associated with increase in use of National Health Service re sources . Further research is required to determine if the reduction in blood pressure is maintained in the longer term and if the intervention is cost effective . Trial registration Current Controlled Trials IS RCT N72614272 BACKGROUND Pharmacist- or nurse-led team care decreases patient blood pressure ( BP ) and cardiovascular disease ( CVD ) risk . PURPOSE To evaluate whether a Web-based dietitian-led ( WD ) team care intervention was feasible and result ed in decreased BP , CVD risk , and weight compared to usual care ( UC ) . METHODS Electronic health record ( EHR ) data identified patients aged 30 - 69 years with BMI > 26 , elevated BP , and 10%-25 % 10-year Framingham CVD risk who were registered patient website users . Patients with uncontrolled BP at screening were r and omized to UC or WD , which included a home BP monitor , scale , and dietitian team care . WD participants had a single in-person dietitian visit to obtain baseline information and create a plan to reduce CVD risk . Planned follow-up occurred via secure messaging to report BP , weight , and fruit and vegetable intake and receive ongoing feedback . If needed , dietitians encouraged patients and their physicians to intensify antihypertensive and lipid-lowering medications . Primary outcomes were change in systolic BP and weight loss ≥4 kg at 6 months . Feasibility outcomes included intervention utilization and satisfaction . RESULTS Between 2010 and 2011 , a total of 90 of 101 participants completed 6-month follow-ups . The WD group had higher rates of secure messaging utilization and patient satisfaction . The WD group lost significantly more weight than the UC group ( adjusted net difference=-3.2 kg , 95 % CI=-5.0 , -1.5 , p<0.001 ) and was more likely to lose ≥4 kg ( adjusted relative risk [RRadj]=2.96 , 95 % CI=1.16 , 7.53 ) . BP control and CVD risk reduction were greater in WD than UC , but differences were not statistically significant . CONCLUSIONS WD intervention was feasible and result ed in decreased weight , BP , and CVD risk . A larger trial is justified . TRIAL REGISTRATION NUMBER Trial Registration Number : NCT01077388 CONTEXT Treating hypertension decreases mortality and disability from cardiovascular disease , but most hypertension remains inadequately controlled . OBJECTIVE To determine if a new model of care that uses patient Web services , home blood pressure ( BP ) monitoring , and pharmacist-assisted care improves BP control . DESIGN , SETTING , AND PARTICIPANTS A 3-group r and omized controlled trial , the Electronic Communications and Home Blood Pressure Monitoring study was based on the Chronic Care Model . The trial was conducted at an integrated group practice in Washington state , enrolling 778 participants aged 25 to 75 years with uncontrolled essential hypertension and Internet access . Care was delivered over a secure patient Web site from June 2005 to December 2007 . INTERVENTIONS Participants were r and omly assigned to usual care , home BP monitoring and secure patient Web site training only , or home BP monitoring and secure patient Web site training plus pharmacist care management delivered through Web communications . MAIN OUTCOME MEASURES Percentage of patients with controlled BP ( < 140/90 mm Hg ) and changes in systolic and diastolic BP at 12 months . RESULTS Of 778 patients , 730 ( 94 % ) completed the 1-year follow-up visit . Patients assigned to the home BP monitoring and Web training only group had a nonsignificant increase in the percentage of patients with controlled BP ( < 140/90 mm Hg ) compared with usual care ( 36 % [ 95 % confidence interval { CI } , 30%-42 % ] vs 31 % [ 95 % CI , 25%-37 % ] ; P = .21 ) . Adding Web-based pharmacist care to home BP monitoring and Web training significantly increased the percentage of patients with controlled BP ( 56 % ; 95 % CI , 49%-62 % ) compared with usual care ( P < .001 ) and home BP monitoring and Web training only ( P < .001 ) . Systolic BP was decreased stepwise from usual care to home BP monitoring and Web training only to home BP monitoring and Web training plus pharmacist care . Diastolic BP was decreased only in the pharmacist care group compared with both the usual care and home BP monitoring and Web training only groups . Compared with usual care , the patients who had baseline systolic BP of 160 mm Hg or higher and received home BP monitoring and Web training plus pharmacist care had a greater net reduction in systolic BP ( -13.2 mm Hg [ 95 % CI , -19.2 to -7.1 ] ; P < .001 ) and diastolic BP ( -4.6 mm Hg [ 95 % CI , -8.0 to -1.2 ] ; P < .001 ) , and improved BP control ( relative risk , 3.32 [ 95 % CI , 1.86 to 5.94 ] ; P<.001 ) . CONCLUSION Pharmacist care management delivered through secure patient Web communications improved BP control in patients with hypertension . Trial Registration clinical trials.gov Identifier : NCT00158639 The White Paper Choosing health acknowledges that there is no lack of information in the system about healthy lifestyles , but the manner of communication of risk and the level of support for lifestyle change need improvement . Action also has to be taken to address inequalities in health and to focus on securing better access to healthier choices for people in disadvantaged groups or areas . Accordingly , this r and omized controlled trial examined whether access to a purpose -built health portal for heart disease could enable patients to manage better their heart conditions . We recruited 108 men and women aged 50—74 from coronary heart disease registries from a deprived area of Greater Manchester . Every participant received a new computer and one-year broadb and subscription ; however , only the experimental group received access to the Hearts of Salford health portal . Our results indicate that the experimental group changed their diet significantly . Specifically , they reported eating ` bad foods ' ( such as chips , sweets , crisps , fried foods , ready meals and cakes/biscuits ) significantly less often compared to the controls |
12,883 | 17,178,018 | All active-treatment arms demonstrated significant improvements in weight and body composition from baseline .
Significant effects between treatment groups were shown only in intervention versus control studies .
Significant weight loss was not accompanied by beneficial changes in cardiovascular risk factors in the majority of studies .
Lifestyle interventions do produce weight loss in overweight postmenopausal women and have the potential to improve disease outcomes associated with overweight | The objective of this systematic review was to determine the effect on long-term health outcomes of lifestyle interventions design ed to produce weight loss in postmenopausal women . | CONTEXT Obesity in the United States has increased dramatically during the past several decades . There is debate about optimum calorie balance for prevention of weight gain , and proponents of some low-carbohydrate diet regimens have suggested that the increasing obesity may be attributed , in part , to low-fat , high-carbohydrate diets . OBJECTIVES To report data on body weight in a long-term , low-fat diet trial for which the primary end points were breast and colorectal cancer and to examine the relationships between weight changes and changes in dietary components . DESIGN , SETTING , AND PARTICIPANTS R and omized intervention trial of 48,835 postmenopausal women in the United States who were of diverse background s and ethnicities and participated in the Women 's Health Initiative Dietary Modification Trial ; 40 % ( 19,541 ) were r and omized to the intervention and 60 % ( 29,294 ) to a control group . Study enrollment was between 1993 and 1998 , and this analysis includes a mean follow-up of 7.5 years ( through August 31 , 2004 ) . INTERVENTIONS The intervention included group and individual sessions to promote a decrease in fat intake and increases in vegetable , fruit , and grain consumption and did not include weight loss or caloric restriction goals . The control group received diet-related education material s. MAIN OUTCOME MEASURE Change in body weight from baseline to follow-up . RESULTS Women in the intervention group lost weight in the first year ( mean of 2.2 kg , P<.001 ) and maintained lower weight than control women during an average 7.5 years of follow-up ( difference , 1.9 kg , P<.001 at 1 year and 0.4 kg , P = .01 at 7.5 years ) . No tendency toward weight gain was observed in intervention group women overall or when stratified by age , ethnicity , or body mass index . Weight loss was greatest among women in either group who decreased their percentage of energy from fat . A similar but lesser trend was observed with increases in vegetable and fruit servings , and a nonsignificant trend toward weight loss occurred with increasing intake of fiber . CONCLUSION A low-fat eating pattern does not result in weight gain in postmenopausal women . Clinical Trial Registration Clinical Trials.gov , NCT00000611 Diet and exercise studies of premenopausal women have shown reductions in obesity and other cardiovascular disease ( CVD ) risk factors . Forty-one healthy , moderately obese ( 120 - 140 % of ideal body weight , LBW ) , postmenopausal women ( 65.6 + /- 3.3 y ) participating in 24-wk diet or diet + exercise programs were studied to determine whether similar CVD risk reduction would occur . Daily energy need ( DEN ) was estimated from basal energy expenditure and self-reported activity . The diet + exercise group ( n = 16 ) reduced their daily energy intake ( DEI ) by 2092 kJ from their DEN and expended 837 kJ/d in walking and resistance exercise . The two diet-only groups ( n = 13 and n = 12 ) reduced their DEI by 2092 and 2929 kJ from their DEN , respectively . Body weight , waist-to-hip and subscapula-to-triceps ratios , blood lipids ( total , low-density-lipoprotein , and high-density-lipoprotein cholesterol , and triacylglycerols ) , glucose , and insulin concentrations were measured at baseline and after 12 and 24 wk of diet and diet + exercise . Data were analyzed by using analysis of variance with repeated measures ( P < or = 0.05 ) and Tukey 's post hoc test . Loss of body weight was significant for all groups between baseline and 12 and 24 wk ( baseline : 79.3 + /- 7.6 kg ; 12 wk ; 75.1 + /- 7.7 kg ; 24 wk ; 72.8 + /- 8.0 kg ) but did not differ among groups . No significant time or treatment effects were observed between baseline and 24 wk for changes in mean blood lipid , glucose , and fasting insulin concentrations or measures of body fat distribution . Although 24 wk of diet or diet+exercise significantly reduced body weight in this group , this loss in body weight was not accompanied by a reduction of other commonly accepted CVD risks BACKGROUND The impact of a 6-month lifestyle change intervention on cardiovascular risk factors in obese , sedentary , postmenopausal women was examined . A secondary aim of this investigation was to determine whether the addition of self-control skills training to an empirically supported lifestyle change intervention would result in greater cardiovascular risk reduction . METHODS Forty-four women were r and omly assigned to receive either a lifestyle change or a lifestyle change with self-control skills intervention . Pretreatment and posttreatment weight loss , body composition , physical activity , cardiorespiratory fitness , diet , blood pressure ( BP ) , blood lipids , and psychosocial functioning were assessed . Also , at 1-year posttreatment , weight loss , body composition , self-reported physical activity , and psychosocial functioning were assessed . RESULTS The women significantly increased their physical activity ( + 39.6 % ) and cardiorespiratory fitness ( + 13.5 % ) and reduced their body weight ( -6.5 % ) , fat mass ( -7.4 % ) , body fat ( -2.4 % ) , BP ( SBP -6.2 % , DBP -9.2 % ) , total cholesterol ( -7.4 % ) , triglycerides ( -16.5 % ) , and low-density lipoprotein ( LDL ) cholesterol ( 9.1 % ) and improved their diet ( p < 0.05 ) . At the 1-year follow-up , women had regained approximately 63 % of their posttreatment weight loss ( p < 0.05 ) , but had maintained their previous increases in physical activity . Additionally , there were no significant changes in fat free mass , body fat , anxiety , or depression between the end of treatment and 1-year posttreatment . The addition of self-control skills training did not significantly improve cardiovascular risk reduction . CONCLUSIONS Lifestyle change interventions may be an effective means for reducing cardiovascular risk in obese , sedentary , postmenopausal women . However , greater attention should be devoted to the maintenance of these positive lifestyle changes The aim of this study was to study the influence of hormone replacement therapy ( HRT ) on weight changes , body composition , and bone mass in early postmenopausal women in a partly r and omized comprehensive cohort study design . A total of 2016 women ages 45 - 58 years from 3 months to 2 years past last menstrual bleeding were included . One thous and were r and omly assigned to HRT or no HRT in an open trial , whereas the others were allocated according to their preferences . All were followed for 5 years for body weight , bone mass , and body composition measurements . Body weight increased less over the 5 years in women r and omized to HRT ( 1.94 + /- 4.86 kg ) than in women r and omized to no HRT ( 2.57 + /- 4.63 , p = 0.046 ) . A similar pattern was seen in the group receiving HRT or not by their own choice . The smaller weight gain in women on HRT was almost entirely caused by a lesser gain in fat . The main determinant of the weight gain was a decline in physical fitness . Women opting for HRT had a significantly lower body weight at inclusion than the other participants , but the results in the self-selected part of the study followed the pattern found in the r and omized part . The change in fat mass was the strongest predictor of bone changes in untreated women , whereas the change in lean body mass was the strongest predictor when HRT was given . Body weight increases after the menopause . The gain in weight is related to a decrease in working capacity . HRT is associated with a smaller increase in fat mass after menopause . Fat gain protects against bone loss in untreated women but not in HRT-treated women . The data suggest that women 's attitudes to HRT are more positive if they have low body weight , but there is no evidence that the conclusions in this study are skewed by selection bias Objective : To evaluate the effect of moderate-intensity exercise on the occurrence and severity of menopause symptoms . Design : A yearlong , r and omized , clinical trial , conducted in Seattle , WA , with 173 overweight , postmenopausal women not taking hormone therapy in the previous 6 months . The intervention was a moderate-intensity exercise intervention ( n = 87 ) versus stretching control group ( n = 86 ) . Using logistic regression , odds ratios comparing exercise with controls were calculated at 3 , 6 , 9 , and 12 months for menopause symptoms and their severity . Results : There was a significant increase in hot flash severity and decreased risk of memory problems in exercisers versus controls over 12 months , although the numbers affected were small . No other significant changes in symptoms were observed . Conclusions : Exercise does not seem to decrease the risk of having menopause symptoms in overweight , postmenopausal women not taking hormone therapy and may increase the severity of some symptoms in a small number of women Postmenopausal women are believed to have a higher risk of coronary artery disease than premenopausal women . In this study , we prospect ively determined changes in coronary risk factors that were attributable to natural menopause in 541 healthy , initially premenopausal women 42 to 50 years of age . After approximately 2 1/2 years , 69 women had spontaneously stopped menstruating for at least 12 months , and 32 women had stopped natural menstruation and received hormone-replacement therapy for a period of at least 12 months . An equal number of age-matched premenopausal women in the study group served as controls . In women who had a natural menopause and did not receive hormone-replacement therapy , serum levels of high-density lipoprotein ( HDL ) cholesterol declined as compared with those of premenopausal controls ( -0.09 vs. 0.00 mmol per liter ; P = 0.01 ) , and levels of low-density lipoprotein ( LDL ) cholesterol increased ( + 0.31 vs. + 0.14 mmol per liter ; P = 0.04 ) . In menopausal women who received hormone-replacement therapy , HDL and LDL cholesterol levels did not change , but the levels of triglycerides ( + 0.42 vs. -0.04 mmol per liter ; P less than 0.001 ) , apolipoprotein A-I ( + 0.18 vs. + 0.03 g per liter ; P less than 0.01 ) , and apolipoprotein A-II ( + 0.05 vs. -0.03 g per liter ; P less than 0.05 ) increased as compared with premenopausal controls . Natural menopause did not affect blood pressure , plasma glucose or insulin levels , body weight , the total number of kilojoules consumed in the diet , or the total number of kilojoules expended in physical activity . These results suggest that a natural menopause has an unfavorable effect on lipid metabolism , which may contribute to an increase in the risk of coronary disease . Hormone-replacement therapy may prevent some of these changes OBJECTIVE To investigate whether fat distribution or sex hormone status in overweight postmenopausal women do influence the response to treatment of overweight . DESIGN Longitudinal , clinical intervention study of a 4.2 MJ diet daily with or without exercise . SUBJECTS 98 healthy , overweight , postmenopausal women ( age : 49 - 58 y , BMI : 25 - 42 kg/m2 ) . MEASUREMENTS Various fatness and fat distribution parameters ( by dual-energy x-ray absorptiometry and anthropometry ) , sex hormone-binding globulin ( SHBG ) , sex hormones , and the resting energy expenditure ( REE ) at baseline and after 3 months . RESULTS Reductions in weight and fat were independent of the initial fat distribution and the REE , but were significantly associated with high initial SHBG levels . Furthermore , loss of fat was significantly and independently associated with increases in SHBG and reductions in central fat distribution . CONCLUSION Postmenopausal women with an and roid and gynoid fat distribution respond with similar weight loss to treatment of overweight . Furthermore , a more healthy , less and roid , fat distribution and sex hormone status may be achieved with increasing weight loss OBJECTIVE The Women 's Health Trial : Feasibility Study in Minority Population s ( WHT : FSMP ) documented that a low-fat diet was associated with a reduced fat intake in older women of diverse ethnic background s. The purpose of the current study was to examine the effect of the low-fat diet on anthropometric and biochemical variables . DESIGN R and omized clinical trial in 2,208 postmenopausal women , 50 to 79 years of age . RESULTS The decrease in fat intake correlated directly with a decrease in body weight ( r=.22 , P<.001 ) . After 6 months , the intervention group had an average weight loss of 1.8 kg . Body mass index decreased 0.7 kg/m2 . Waist circumference decreased 1.8 cm . All of these changes were statistically significant , compared to changes in the control group ( P<.01 ) . Changes in systolic ( -3.1 mm Hg ) and diastolic ( -1.1 mm Hg ) blood pressures ( BP ) occurred in the intervention group . The decrease in systolic BP reached statistical significance ( P=.02 ) , relative to the control group . Decreases in plasma glucose were small ( -0.2 mmol/L ) in the intervention group , although there was a trend for difference from the control group ( P=.11 ) . Decreases in serum insulin levels were small ( -0.5 microIU/mL ) in the intervention group , although there was , again , a trend for difference from the control group . CONCLUSIONS In older White , Black , and Hispanic women , a long-term low-fat dietary intervention was accompanied by modest , but statistically significant , decreases in body weight and anthropometric indices , without any particular attempt being made to reduce calories . Changes in glucose and insulin were small . The long-term biological significance of the glucose and insulin changes is unknown Background : The American College of Sports Medicine recommends 20–60 minutes of aerobic exercise three to five days a week at an intensity of 40/50–85 % of maximal aerobic power ( Vo2max ) reserve , expending a total of 700–2000 kcal ( 2.93–8.36 MJ ) a week to improve aerobic power and body composition . Objective : To ascertain the minimum effective dose of exercise . Methods : Voluntary , healthy , non-obese , sedentary , postmenopausal women ( n = 121 ) , 48–63 years of age , were r and omised to four low dose walking groups or a control group ; 116 subjects completed the study . The exercise groups walked five days a week for 24 weeks with the following intensity ( % of Vo2max ) and energy expenditure ( kcal/week ) : group W1 , 55%/1500 kcal ; group W2 , 45%/1500 kcal ; group W3 , 55%/1000 kcal ; group W4 , 45%/1000 kcal . Vo2max was measured in a direct maximal treadmill test . Submaximal aerobic fitness was estimated as heart rates at submaximal work levels corresponding to 65 % and 75 % of the baseline Vo2max . The body mass index ( BMI ) was calculated and percentage of body fat ( F% ) estimated from skinfolds . Results : The net change ( the differences between changes in each exercise group and the control group ) in Vo2max was 2.9 ml/min/kg ( 95 % confidence interval ( CI ) 1.5 to 4.2 ) in group W1 , 2.6 ml/min/kg ( 95 % CI 1.3 to 4.0 ) in group W2 , 2.4 ml/min/kg ( 95 % CI 0.9 to 3.8 ) in group W3 , and 2.2 ml/min/kg ( 95 % CI 0.8 to 3.5 ) in group W4 . The heart rates in st and ard submaximal work decreased 4 to 8 beats/min in all the groups . There was no change in BMI , but the F% decreased by about 1 % unit in all the groups . Conclusions : Walking ( for 24 weeks ) at moderate intensity 45 % to 55 % of Vo2max , with a total weekly energy expenditure of 1000–1500 kcal , improves Vo2max and body composition of previously sedentary , non-obese , postmenopausal women . This dose of exercise apparently approaches the minimum effective dose OBJECTIVE : To investigate in a population -based r and om sample of postmenopausal women the adjusted association of visceral adipose tissue ( VAT ) with coronary risk factors . DESIGN : Cross-sectional population -based r and om sample study .SUBJECTS : Ninety-eight postmenopausal women ( age 50–65 y ) . MEASUREMENTS : Visceral and subcutaneous fat areas by computer axial tomography , anthropometry , lipid profile , fasting glucose and insulin , diet , physical activity , smoking status and alcohol intake . RESULTS : Compared to women with low VAT , women with high VAT ( > 117.8 cm2 ) had a less favorable metabolic profile with significantly higher fasting glucose ( 120±50 vs 98±39 ) , insulin ( 7.9±10 vs 5±8 ) , triglycerides ( 172±69 vs 127±72 ) , apolipoprotein B ( 119±24 vs 98±32 ) and significantly lower HDL-C ( 38±10 vs 46±14 ) values in the whole sample ( n=98 ) . A similar profile was found in women without diabetes and hypertension ( n=39 ) . In multiple regression models , VAT explained a portion of the variance of TG ( 6.2 % ) in the entire sample and of total cholesterol ( 12.4 % ) , LDL-C ( 15.8 % ) , triglycerides ( 16.3 % ) , apolipoprotein B ( 11.6 % ) , and fasting glucose ( 28.4 % ) in the group of non-diabetic or hypertensive women . Our VAT cut-off point of 117.8 cm2 corresponded to a waist circumference of 84 cm . CONCLUSION : Our results in a r and om population -based sample of postmenopausal women confirm the association of VAT with most coronary risk factors . These associations persisted after adjusting for diet , physical activity , smoking status and alcohol intake BACKGROUND Guidelines established by the National Cholesterol Education Program ( NCEP ) promote exercise and weight loss for the treatment of abnormal lipoprotein levels . Little is known , however , about the effects of exercise or the NCEP diet , which is moderately low in fat and cholesterol , in persons with lipoprotein levels that place them at high risk for coronary heart disease . METHODS We studied plasma lipoprotein levels in 180 postmenopausal women , 45 through 64 years of age , and 197 men , 30 through 64 years of age , who had low high-density lipoprotein ( HDL ) cholesterol levels ( < or = 59 mg per deciliter in women and < or = 44 mg per deciliter in men ) and moderately elevated levels of low-density lipoprotein ( LDL ) cholesterol ( > 125 mg per deciliter but < 210 mg per deciliter in women and > 125 mg per deciliter but < 190 mg per deciliter in men ) . The subjects were r and omly assigned to aerobic exercise , the NCEP Step 2 diet , or diet plus exercise , or to a control group , which received no intervention . RESULTS Dietary intake of fat and cholesterol decreased during the one-year study ( P<0.001 ) , as did body weight , in women and men in either the diet group or the diet-plus-exercise group , as compared with the controls ( P<0.001 ) and the exercise group ( P<0.05 ) , in which dietary intake and body weight were unchanged . Changes in HDL cholesterol and triglyceride levels and the ratio of total to HDL cholesterol did not differ significantly among the treatment groups , for subjects of either sex . The serum level of LDL cholesterol was significantly reduced among women ( a decrease of 14.5+/-22.2 mg per deciliter ) and men ( a decrease of 20.0+/-17.3 mg per deciliter ) in the diet-plus-exercise group , as compared with the control group ( women had a decrease of 2.5+/-16.6 mg per deciliter , P<0.05 ; men had a decrease of 4.6+/-21.1 mg per deciliter , P<0.001 ) . The reduction in LDL cholesterol in men in the diet-plus-exercise group was also significant as compared with that among the men in the exercise group ( 3.6+/-18.8 mg per deciliter , P<0.001 ) . In contrast , changes in LDL cholesterol levels were not significant among the women ( a decrease of 7.3+/-18.9 mg per deciliter ) or the men ( 10.8+/-18.8 mg per deciliter ) in the diet group , as compared with the controls . CONCLUSIONS The NCEP Step 2 diet failed to lower LDL cholesterol levels in men or women with high-risk lipoprotein levels who did not engage in aerobic exercise . This finding highlights the importance of physical activity in the treatment of elevated LDL cholesterol levels INTRODUCTION This analysis was conducted to study the effect of a 1-yr moderate-intensity aerobic exercise program on serum lipoproteins among overweight/obese postmenopausal women . METHODS We r and omized 173 sedentary ( VO2max = 20.2 mL.kg(-1).min(-1 ) ) , overweight/obese women ( body mass index ( BMI ) 25.0 - 42.0 kg.m(-2 ) or body fat > 33 % if BMI 24.0 - 25.0 ) aged 50 - 75 yr , not using hormone therapy , living in the Seattle area , to an exercise intervention or stretching control group . The exercise intervention included facility and home-based exercise ( 45 min , 5 d.wk(-1 ) of moderate-intensity sports or recreational exercise ) . Total cholesterol ( TC ) , triglycerides , and high-density lipoprotein ( HDL ) were determined by chemical assay ; low-density lipoprotein ( LDL ) was then calculated . RESULTS Of the 173 women , 170 ( 98.3 % ) completed the study with exercisers averaging 176 ( SD 91 ) min.wk(-1 ) of moderate- to vigorous-intensity ( 60%-75 % HRmax ) exercise , expending approximately 3828 kJ.wk(-1 ) ( SD 2053 ) . Exercisers , compared with stretchers , significantly increased their VO2max ( + 11 % , P<0.001 ) and lost more body weight ( -1.4 kg , P < 0.05 ) , DEXA-% total body fat ( -1.0 , P < 0.005 ) , L4 - 5 computed tomography intraabdominal fat ( -8.6 cm2 , P < 0.05 ) and subcutaneous abdominal fat ( -28.8 cm2 , P < 0.005 ) after 12 months . Mean ( SD ) baseline lipoprotein levels for TC , LDL , HDL , and triglycerides were 231 ( 39 ) , 152 ( 39 ) , 52 ( 12 ) , and 135 ( 65 ) mg.dL(-1 ) , respectively . We observed no significant change in serum lipoprotein levels among exercisers compared with stretchers at either 3 or 12 months postr and omization . We did not observe a statistically significant effect of exercise on serum lipoproteins in subgroups that changed their intraabdominal and subcutaneous fat , percent total body fat , or VO2max the most , or that adhered to the exercise regimen the most over 1 yr . CONCLUSION It appears that a year long moderate-intensity exercise program alone does not significantly alter serum lipoprotein levels among overweight/obese postmenopausal women Preliminary evidence from a case control study of healthy postmenopausal women living in Palermo , Sicily , is presented to investigate the potential impact of a traditional Mediterranean diet on the risk of developing breast cancer . Of the 230 women who fulfilled specific eligibility criteria , 115 were enrolled in the study based on serum testosterone values equal to or greater than the median population value ( 0.14 microg/ml ) . Women were then individually r and omized into a diet intervention ( n = 58 ) and a control ( n = 55 ) group . Women in the intervention group attended a weekly " cooking course " for 1 year , being trained by professional chefs in the correct use of the natural ingredients of the traditional Mediterranean diet , including whole cereals , legumes , seeds , fish , cruciferous vegetables , and many others . The intervention group was subsequently instructed to follow the learned diet at home , while the control group was only advised to increase the consumption of fruits and vegetables , as recommended by WHO . The following measures were taken at the beginning , middle , and end of the study : ( a ) fasting blood and 12-hour urine sample s to assay defined hormonal endpoints ; ( b ) height , weight , and circumference of the waist and hip ; and ( c ) a food frequency and computerized 24-hour dietary recall question naire . After 1 year , both the control and the intervention groups showed satisfactory compliance rates ( 81 and 85 % , respectively ) . In addition , preliminary results so far obtained reveal an unequivocal trend towards weight loss , a strong reduction in cholesterol levels , and a psychophysical feeling of well-being by women adopting the Mediterranean diet . The study is currently ongoing to verify the association of changes in serum and urine hormone levels and breast cancer risk in the intervention group OBJECTIVE To evaluate the potential benefits of programmed Tai Chi Chun ( TCC ) exercise on the weight-bearing bones of early postmenopausal women . DESIGN Age-matched and r and omized prospect i ve intervention . SETTING University medical school . PARTICIPANTS One hundred thirty-two healthy postmenopausal women ( mean age , 54.0+/-3.5y ) within 10 years of menopause onset were recruited and r and omized into the TCC exercise group ( n=67 ) or the sedentary control group ( n=65 ) . INTERVENTION Supervised TCC exercise was performed by the TCC group for 45 minutes a day , 5 days a week , for 12 months ; control subjects retained a sedentary life style . Main outcome measures Bone mineral density ( BMD ) was measured in the lumbar spine and proximal femur by using dual-energy x-ray absorptiometry and in the distal tibia by using multislice peripheral quantitative computed tomography ( pQCT ) . All BMD measurements were repeated after 12 months in both groups . Fracture rate was also documented . RESULTS Baseline measurements showed homogeneity in age , anthropometric variables , and menstruation status between the TCC and control groups . Exactly 81.6 % of the subjects in the TCC group and 83.1 % of subjects in the control group completed the 12-month follow-up study . BMD measurements revealed a general bone loss in both TCC and sedentary control subjects at all measured skeletal sites , but with a reportedly slower rate in the TCC group . A significant 2.6- to 3.6-fold retardation of bone loss ( P<.01 ) was found in both trabecular and cortical compartments of the distal tibia in the TCC group as compared with the controls , as measured by pQCT . A total of 4 fracture cases were documented during follow-up , including 3 subjects in the control group and 1 in the TCC group . CONCLUSIONS This is the first prospect i ve and r and omized study to show that a programmed TCC exercise intervention is beneficial for retarding bone loss in weight-bearing bones in early postmenopausal women . Long-term follow-up is needed to substantiate the role of TCC exercise in the prevention of osteoporosis and its related fracture OBJECTIVE --To determine the effectiveness of group- vs home-based exercise training of higher and lower intensities among healthy , sedentary older adults . DESIGN --Year-long r and omized , controlled trial comparing ( 1 ) higher-intensity group-based exercise training ; ( 2 ) higher-intensity home-based exercise training ; ( 3 ) lower-intensity home-based exercise training ; or ( 4 ) assessment -only control . SETTING --General community located in northern California . PARTICIPANTS --One hundred sixty women and 197 men 50 to 65 years of age who were sedentary and free of cardiovascular disease . One out of nine persons contacted through a community r and om-digit-dial telephone survey and citywide promotion were r and omized . INTERVENTIONS --For higher-intensity exercise training , three 40-minute endurance training sessions per week were prescribed at 73 % to 88 % of peak treadmill heart rate . For lower-intensity exercise training , five 30-minute endurance training sessions per week were prescribed at 60 % to 73 % of peak treadmill heart rate . MAIN OUTCOME MEASURES --Treadmill exercise test performance , exercise participation rates , and heart disease risk factors . RESULTS --Compared with controls , subjects in all three exercise training conditions showed significant improvements in treadmill exercise test performance at 6 and 12 months ( P less than .03 ) . Lower-intensity exercise training achieved changes comparable with those of higher-intensity exercise training . Twelve-month exercise adherence rates were better for the two home-based exercise training conditions relative to the group-based exercise training condition ( P less than .0005 ) . There were no significant training-induced changes in lipid levels , weight , or blood pressure . CONCLUSIONS --We conclude that ( 1 ) this community-based exercise training program improved fitness but not heart disease risk factors among sedentary , healthy older adults ; ( 2 ) home-based exercise was as effective as group exercise in producing these changes ; ( 3 ) lower-intensity exercise training was as effective as higher-intensity exercise training in the home setting ; and ( 4 ) the exercise programs were relatively safe BACKGROUND A number of factors contribute to increased risk of coronary heart disease ( CHD ) among postmenopausal women , including atherogenic changes in serum cholesterol profiles , weight gain , and decreases in physical activity during the menopause . To date , no study has attempted to prevent elevations in primary CHD risk factors as women experience menopause . METHODS A sample of 535 healthy premenopausal women , ages 44 - 50 , were recruited for an ongoing 5-year r and omized prevention trial testing whether increases in low-density lipoprotein cholesterol ( LDL-C ) and body weight can be prevented during the menopause with a dietary and behavioral intervention . The aim was to reduce total dietary and saturated fat and cholesterol , prevent weight gain , and increase physical activity levels . Changes in CHD risk factors after the first 6 months of treatment were analyzed comparing 253 intervention and 267 assessment -only control participants . RESULTS The intervention group showed significant reductions in total cholesterol ( -0.34 mmol/liter ) , LDL-C ( -0.28 mmol/liter ) , triglycerides ( -0.04 mmol/liter ) , weight ( -4.8 kg ) , waist-hip ratio ( -0.008 ) , systolic blood pressure ( -3.5 mm Hg ) , diastolic blood pressure ( -2.2 mm Hg ) , serum glucose levels ( -0.06 mmol/liter ) , and HDL-C ( -0.06 mmol/liter ) and significant increases in physical activity ( + 383 kcal ) . No significant changes were observed in the control group . CONCLUSION Six-month results suggested that participants were receptive to the preventive approach to CHD risk reduction and were successful in making initial positive lifestyle changes . Follow-up data will evaluate long-term adherence to the intervention and the interaction between adherence and physiological changes during menopause CONTEXT The hypothesis that a low-fat dietary pattern can reduce breast cancer risk has existed for decades but has never been tested in a controlled intervention trial . OBJECTIVE To assess the effects of undertaking a low-fat dietary pattern on breast cancer incidence . DESIGN AND SETTING A r and omized , controlled , primary prevention trial conducted at 40 US clinical centers from 1993 to 2005 . PARTICIPANTS A total of 48,835 postmenopausal women , aged 50 to 79 years , without prior breast cancer , including 18.6 % of minority race/ethnicity , were enrolled . INTERVENTIONS Women were r and omly assigned to the dietary modification intervention group ( 40 % [ n = 19,541 ] ) or the comparison group ( 60 % [ n = 29,294 ] ) . The intervention was design ed to promote dietary change with the goals of reducing intake of total fat to 20 % of energy and increasing consumption of vegetables and fruit to at least 5 servings daily and grains to at least 6 servings daily . Comparison group participants were not asked to make dietary changes . MAIN OUTCOME MEASURE Invasive breast cancer incidence . RESULTS Dietary fat intake was significantly lower in the dietary modification intervention group compared with the comparison group . The difference between groups in change from baseline for percentage of energy from fat varied from 10.7 % at year 1 to 8.1 % at year 6 . Vegetable and fruit consumption was higher in the intervention group by at least 1 serving per day and a smaller , more transient difference was found for grain consumption . The number of women who developed invasive breast cancer ( annualized incidence rate ) over the 8.1-year average follow-up period was 655 ( 0.42 % ) in the intervention group and 1072 ( 0.45 % ) in the comparison group ( hazard ratio , 0.91 ; 95 % confidence interval , 0.83 - 1.01 for the comparison between the 2 groups ) . Secondary analyses suggest a lower hazard ratio among adherent women , provide greater evidence of risk reduction among women having a high-fat diet at baseline , and suggest a dietary effect that varies by hormone receptor characteristics of the tumor . CONCLUSIONS Among postmenopausal women , a low-fat dietary pattern did not result in a statistically significant reduction in invasive breast cancer risk over an 8.1-year average follow-up period . However , the nonsignificant trends observed suggesting reduced risk associated with a low-fat dietary pattern indicate that longer , planned , nonintervention follow-up may yield a more definitive comparison . CLINICAL TRIALS REGISTRATION Clinical Trials.gov Identifier : NCT00000611 |
12,884 | 23,169,897 | Results found mixed relationships between PCC and clinical outcomes , that is , some studies found significant relationships between specific elements of PCC and outcomes but others found no relationship .
There was stronger evidence for positive influences of PCC on satisfaction and self-management . | Patient-centered care ( PCC ) has been studied for several decades .
Yet a clear definition of PCC is lacking , as is an underst and ing of how specific PCC processes relate to patient outcomes .
We conducted a systematic review of the PCC literature to examine the evidence for PCC and outcomes . | A clinical r and omized study ( posttest design ) was conducted to examine whether patient-centered care ( PCC ) impacts patient satisfaction , perception of nursing care , and quality of care . Differences were seen in 2 of 3 subscales within the Baker and Taylor Measurement Scale . The PCC group rated satisfaction ( P = .04 ) and quality of services ( P = .03 ) higher than controls . PCC may impact patients ' perception of the level of satisfaction and quality of care received Abstract OBJECTIVE : There is a well-documented gap between diabetes care guidelines and the services received by patients in almost all health care setting s. This project reports initial results from a computer-assisted , patient-centered intervention to improve the level of recommended services received by patients from a wide variety of primary care providers . DESIGN AND SETTING S : Eight hundred eighty-six patients with type 2 diabetes under the care of 52 primary care physicians participated in the Diabetes Priority Program . Physicians were stratified and r and omized to intervention or control conditions and evaluated on 2 primary outcomes : number of recommended laboratory screenings and recommended patient-centered care activities completed . Secondary outcomes were evaluated using the Problem Areas in Diabetes scale and the Patient Health Question naire (PHQ)-9 depression scale , and the RE- AIM framework was used to evaluate potential for dissemination . RESULTS : The program was well-implemented and significantly improved both number of recommended laboratory assays ( 3.4 vs 3.1 ; P<.001 ) and patient-centered aspects of diabetes care patients received ( 3.6 vs 3.2 ; P<.001 ) compared to those in r and omized control practice s. Activities that were increased most were foot exams ( follow-up rates of 80 % vs 52 % ; P<.003 ) and nutrition counseling ( 76 % vs 52 % ; P<.001 ) . CONCLUSIONS : Patients are very willing to participate in a brief computer-assisted intervention that is effective in enhancing quality of diabetes care . Staff in primary care offices can consistently deliver an intervention of this nature , but most physicians were unwilling to participate in this translation research study BACKGROUND Recent studies have suggested that there is a positive impact of patient-centered care ( PCC ) on both the patient-physician relationship and subsequent patient health-related behaviors . One recent prospect i ve study reported a significant relationship between the degree of PCC experienced by patients during their hospitalization for acute myocardial infa rct ion ( AMI ) and their postdischarge cardiac symptoms . A limitation of this study , however , was a lack of information regarding the technical quality of the AMI care , which might have explained at least part of the differences in outcomes . The present study was undertaken to test the influence of both PCC and technical care quality on outcomes among AMI patients . METHODS We analyzed data from a national sample of 1,858 veterans hospitalized for an initial AMI in a Department of Veterans Affairs medical center during fiscal years 2003 and 2004 for whom data had been compiled on evidence -based treatment and who had also completed a Picker question naire assessing perceptions of PCC . Cox proportional hazards models were used to estimate the relationship between PCC and survival 1-year postdischarge , controlling for technical quality of care , patient clinical condition and history , admission process characteristics , and patient sociodemographic characteristics . We hypothesized that better PCC would be associated with a lower probability of death 1-year postdischarge , even after controlling for patient characteristics and the technical quality of care . RESULTS Better PCC was associated with a significantly but modestly lower hazard of death over the 1-year study period ( hazard ratio 0.992 , 95 percent confidence interval 0.986 - 0.999 ) . CONCLUSIONS Providing PCC may result in important clinical benefits , in addition to meeting patient needs and expectations BACKGROUND Patient-centered Assessment and Counseling on Exercise plus nutrition ( PACE+ ) is an intervention based in primary care setting s to help patients change physical activity and dietary behaviors . METHODS One hundred seventy-three adults were assessed before and after a 4-month intervention . All patients completed a computerized assessment and created tailored " action plans " to change one physical activity and one nutrition behavior that they then discussed with their provider . After the visit , subjects were r and omized to one of four extended intervention conditions : control , mail only , infrequent phone and mail , and frequent phone and mail . Self-report of five target behaviors ( moderate and vigorous physical activity stage of change , dietary fat , fruit/vegetable intake , and overeating behaviors ) was collected at baseline and 4 months . Acceptability measures were also taken . RESULTS Participants in all conditions improved on all behaviors over time , supporting the utility of the computer and provider counseling components . The extended intervention did not produce differential results with respect to mode ( phone or mail ) or intensity ( frequent or infrequent ) . However , for each behavior , participants who targeted the behavior to change improved significantly more than those who did not target the behavior . Acceptability of the intervention was high . CONCLUSIONS Primary care-based , interactive health communication to improve physical activity and dietary behavior is feasible and has promising initial results The aim of this paper is to assess whether patient-centred consultations are more effective than the usual style of consultations used by general practitioners with patients suffering from benign chronic musculoskeletal pain and fibromyalgia . It also seeks to evaluate the differential characteristics of these two clinical groups of symptoms . The study was design ed as a cluster r and omised and simple blind trial . Twenty general practitioners took part and 110 patients were recruited . Compared with patients who received the usual treatment from their family physician , those who received a patient-centred approach showed greater improvement after 1 year in terms of psychological distress ( anxiety ) and number of tender points , as well as showing positive trends in some important outcomes such as pain intensity . Significantly better results were observed in those patients suffering chronic pain than in those with fibromyalgia , particularly as regards associated symptoms , self-rated pain and physical mobility as measured by the Nottingham health profile OBJECTIVE To study the effects of a comprehensive discharge planning protocol , design ed specifically for the elderly and implemented by nurse specialists , on patient and caregiver outcomes and cost of care . DESIGN R and omized clinical trial . SETTING Hospital of the University of Pennsylvania . PATIENTS 276 patients and 125 caregivers . Patients were 70 years and older and were placed in selected medical and surgical cardiac diagnostic-related groups . MEASUREMENTS Group differences in patient outcomes ( length of initial hospital stay , length of time between initial hospital discharge and readmission , and rehospitalization rates ) and charges for care ( charges for initial hospitalization , rehospitalizations , health services after discharge , and nurse specialist services ) were measured 2 , 6 , and 12 weeks after discharge . RESULTS From the initial hospital discharge to 6 weeks after discharge , patients in the medical intervention group had fewer readmissions , fewer total days rehospitalized , lower readmission charges , and lower charges for health care services after discharge . No differences in these outcomes were found between the surgical intervention and control groups during this period . CONCLUSIONS Study findings support the need for comprehensive discharge planning design ed for the elderly and implemented by nurse specialists to improve their outcomes after hospital discharge and to achieve cost savings . The findings also suggest that this intervention had its greatest effect in delaying or preventing rehospitalization of patients in the medical intervention group during the first 6 weeks after discharge In a r and omised trial , general practitioners and nurses in 21 practice s were trained in patient-centred consulting and use of material s for people with Type 2 diabetes ( GPs 0.5 days ; nurses 1.5 days ; two optional follow-up half-days ) . Twenty practice s formed the comparison group . Professional beliefs , attitudes and behaviour were measured ( pre-trial , close-of-course and end-of-trial ) , supported by patient reports of nurse behaviour ( 141 trained : 108 comparison patients , 1 year after diagnosis ) . A total of 49 practice nurses responded ( 29 trained ; 20 comparison ) . Trained nurses rated relative importance of patient-centred to professional-centred care as greater than comparison nurses . Trained nurses became less keen on the approach during the trial , and perceived time constraints persisted . Patients diagnosed later in the study were less likely to recognise intervention material s. Trained nurses rated delivery of important aspects of care and satisfaction with style of care as lower than comparison nurses , but patients were more positive about delivery of care from trained than comparison nurses . Although nurses rated patient-centred care as important , whether or not they had been trained as part of the trial , the short , generalizable training programme significantly reduced nurse perceptions of their ability to deliver it . Nonetheless , patients reported that important aspects of diabetes care were delivered more if their nurses had been trained in patient-centred consulting . This raises issues concerning measurement scales completed by trained professionals Background : Among breast cancer patients , tamoxifen use is associated with reduced risk of disease relapse and death , but it is often difficult for women to sustain therapy during the 5 years required to obtain maximum benefit . Objectives : We sought to examine the influence of patient-centered care activities on ongoing tamoxifen use 4 years after initiation , we examined key components of patient-centered care and rates of ongoing tamoxifen . Methods : Using a prospect i ve cohort study that included observational data from the National Initiative for Cancer Care Quality ( NICCQ ) , we studied 881 patients with stage I-III breast cancer who were registered with an initial diagnosis in 1998 by an American College of Surgeons-approved hospital cancer registry in 1 of 5 metropolitan areas , who initiated tamoxifen treatment . A patient survey and medical record abstract ion were used as measurements . Results : Among women who initiated tamoxifen , 79 % were still taking it 4 years later . Other than older age and the severity of side effects , other demographic , clinical and cancer characteristics , and treatments did not predict ongoing tamoxifen use . In contrast , after adjusting for these factors , the proportion of patients with ongoing tamoxifen use was lower for patients reporting less support than needed ( 82 % vs. 69 % , P = 0.0051 ) , less than wanted role in decision-making ( 80 % vs. 70 % , P = 0.0486 ) , decision-making about tamoxifen without doctor input ( 79 % vs. 64 % , P = 0.0182 ) , and for patients who were n't told about side effects in advance ( 82 % vs. 72 % , P = 0.0016 ) . Conclusions : Although age and the severity of side-effects remain important , patient-centered care was a primary mediator of patient adherence to ongoing cancer treatment with tamoxifen BACKGROUND Older persons frequently experience a decline in function following an acute medical illness and hospitalization . OBJECTIVE To test the hypothesis that a multicomponent intervention , called Acute Care for Elders ( ACE ) , will improve functional outcomes and the process of care in hospitalized older patients . DESIGN R and omized controlled trial . SETTING Community teaching hospital . PATIENTS A total of 1,531 community-dwelling patients , aged 70 or older , admitted for an acute medical illness between November 1994 and May 1997 . INTERVENTION ACE includes a specially design ed environment ( with , for example , carpeting and uncluttered hallways ) ; patient-centered care , including nursing care plans for prevention of disability and rehabilitation ; planning for patient discharge to home ; and review of medical care to prevent iatrogenic illness . MEASUREMENTS The main outcome was change in the number of independent activities of daily living ( ADL ) from 2 weeks before admission ( baseline ) to discharge . Secondary outcomes included re source use , implementation of orders to promote function , and patient and provider satisfaction . RESULTS Self-reported measures of function did not differ at discharge between the intervention and usual care groups by intention-to-treat analysis . The composite outcome of ADL decline from baseline or nursing home placement was less frequent in the intervention group at discharge ( 34 % vs 40 % ; P = .027 ) and during the year following hospitalization ( P = .022 ) . There were no significant group differences in hospital length of stay and costs , home healthcare visits , or readmissions . Nursing care plans to promote independent function were more often implemented in the intervention group ( 79 % vs 50 % ; P = .001 ) , physical therapy consults were obtained more frequently ( 42 % vs 36 % ; P = .027 ) , and restraints were applied to fewer patients ( 2 % vs 6 % ; P = .001 ) . Satisfaction with care was higher for the intervention group than the usual care group among patients , caregivers , physicians , and nurses ( P < .05 ) . CONCLUSIONS ACE in a community hospital improved the process of care and patient and provider satisfaction without increasing hospital length of stay or costs . A lower frequency of the composite outcome ADL decline or nursing home placement may indicate potentially beneficial effects on patient outcomes BACKGROUND We design ed this observational cohort study to assess the association between patient-centered communication in primary care visits and subsequent health and medical care utilization . METHODS We selected 39 family physicians at r and om , and 315 of their patients participated . Office visits were audiotaped and scored for patient-centered communication . In addition , patients were asked for their perceptions of the patient-centeredness of the visit . The outcomes were : ( 1 ) patients ' health , assessed by a visual analogue scale on symptom discomfort and concern ; ( 2 ) self-report of health , using the Medical Outcomes Study Short Form-36 ; and ( 3 ) medical care utilization variables of diagnostic tests , referrals , and visits to the family physician , assessed by chart review . The 2 measures of patient-centeredness were correlated with the outcomes of visits , adjusting for the clustering of patients by physician and controlling for confounding variables . RESULTS Patient-centered communication was correlated with the patients ' perceptions of finding common ground . In addition , positive perceptions ( both the total score and the subscore on finding common ground ) were associated with better recovery from their discomfort and concern , better emotional health 2 months later , and fewer diagnostic tests and referrals . CONCLUSIONS Patient-centered communication influences patients ' health through perceptions that their visit was patient centered , and especially through perceptions that common ground was achieved with the physician . Patient-centered practice improved health status and increased the efficiency of care by reducing diagnostic tests and referrals BACKGROUND Hospitals have adopted patient-centered practice s that focus on patients ' needs , values , and preferences in hopes of improving quality and controlling costs . Patient-centered practice s are intended to involve patients in treatment decisions , increase communication between patients and care-givers , and increase interaction with family members and friends . Rapid adoption of these practice s has occurred , even though little is known about the effects of patient-centered care on outcomes and cost . METHODS A simultaneous equations regression model was developed to examine the reciprocal relationships between patient-centeredness , outcomes , and cost . A consortium of employers obtained data from 52 hospital units in southeastern Michigan . Two hundred r and omly selected patients were sample d from all discharges on the medical , surgical , and obstetric units at each hospital for the first three months of 1997 ; the patients were sent the survey in May. Patient-centeredness was measured by patient reports of whether key clinical events occurred ( The Picker Inpatient Survey ) . Outcomes were assessed by rates of unexpected mortality and complications . Cost was defined by self-insured purchaser payments . RESULTS Hospital units that were more patient centered were associated with statistically significantly better outcomes and higher costs than those that were less patient centered . The joint relations between outcomes and cost were insignificant . CONCLUSIONS Patient-centeredness was associated with better outcomes and higher cost . For either the short run or long run , managers , patients , and purchasers should determine whether the improvement in outcomes and patient satisfaction associated with becoming patient centered is worth the investment in costs M eeting the complex needs of patients with chronic illness or impairment is the single greatest challenge facing organized medical practice . Usual care is not doing the job ; dozens of surveys and audits have revealed that sizable proportions of chronically ill patients are not receiving effective therapy , have poor disease con- trol , and are unhappy with their care ( 1 ) . Results of r and omized trials also show that effective disease management programs can achieve substantially better outcomes than usual care , the control intervention . These trials , along with the ideas and efforts for improvement discussed in this issue , show that we can improve care and outcomes . As the articles suggest , these improvements will not come easily . If we are to improve care for most patients with chronic illness , the evidence strongly suggests that we reshape our ambulatory care systems for this purpose . Pri- mary care practice was largely design ed to provide ready access and care to patients with acute , varied problems , with an emphasis on triage and patient flow ; short appointments ; diagnosis and treatment of symptoms and signs ; reliance on laborato- ry investigations and prescriptions ; brief , didactic patient education ; and patient- initiated follow-up . Patients and families struggling with chronic illness have differ- ent needs , and these needs are unlikely to be met by an acute care organization and culture . They require planned , regular interactions with their caregivers , with a focus on function and prevention of exacerbations and complications . This interac- tion includes systematic assessment s , attention to treatment guidelines , and behav- iorally sophisticated support for the patient 's role as self-manager . These interactions must be linked through time by clinical ly relevant information systems and continu- ing follow-up initiated by the medical practice . Comprehensive System Objective : The aim of this study was to determine if nurses , using patient-centered care ( PCC ) , affect patient satisfaction , perceptions of nursing care , and quality outcomes . Background : The Institute of Medicine proposed PCC as 1 of 6 national quality aims , whereas the Centers for Medicare and Medicaid Services highlighted integration of PCC as 1 of 12 actions for quality improvement . Methods : A total of 116 patients were r and omized into an intervention ( PCC ) or control group . Patients who were to receive PCC were called before admission and cared for by nurses who trained to administer/ practice PCC . Control patients received usual care . Both groups completed question naires and received postdischarge calls . Length of stay , falls , infections , and adverse events were measured to assess quality of care . Results : No significant differences were found between groups for length of stay , infection , falls , postoperative complications , quality of care , satisfaction level , or perceptions of nursing care . Conclusions : Patient-centered care did not affect patient 's level of satisfaction or quality of care . However , findings yielded clinical ly relevant results regarding patient/staff responses BACKGROUND In 1991 Beth Israel Hospital ( Boston ) joined nine other hospitals in using the Picker/Commonwealth survey instrument to tap patients perceptions of their hospitalization experience . Beth Israel focused on one of the nine dimensions of the instrument-continuity and transition ( discharge planning ) . FOUR WORK TEAMS : In 1992 four multidisciplinary work teams were formed-for cardiac surgical patients , stroke patients , patients on a medical unit , and patients on a medical and surgical unit . Each team conducted a patient/family discussion group , during which recently discharged patients and their families were asked about their preparation for discharge and asked for input on how to improve the process . INTERVENTIONS Each work team developed interventions on the basis of information specific to their patients . The cardiac work team , for example , developed interdisciplinary practice guidelines for patient care management for the entire postoperative period ; the guidelines include a patient education component on what patients and families can expect during hospitalization . OUTCOMES Clinicians practice differently , inviting more patient feedback and other involvement in care , as a results of their involvement in the project . On the first annual patient survey , administered in 1994 , only 6 % of 1,179 r and omly selected patients ( versus 20 % of the 100 patients first surveyed in 1993 ) indicated that they did not receive the information they needed to help themselves recover . CURRENT PROGRESS AND FUTURE DIRECTIONS : A st and ardized teaching packet containing material developed during the discharge planning improvement project is now distributed . In May 1995 the nursing department launched a patient and family learning center to better meet the health education needs of patients Background . It has not been demonstrated that the implementation of computerized quality improvement strategies can improve client-centered outcomes in public community based , long-term care ( CBLTC ) programs . Objectives . To test and evaluate 2 innovative computer-assisted , client-centered quality improvement strategies for public community-based , long-term care . The first strategy , the Normative Treatment Planning ( NTP ) program , assesses needs , prescribes services , and evaluates outcomes . The second strategy , the Client Feedback System ( CFS ) program , provides service vendors with feedback on client perceptions of services . Research Design . A 2 × 2 factorial design with the 2 strategies using cluster r and omization . Subjects . A total of 2222 clients ( 86 % of eligible program clients ) enrolled in Indiana ’s state case management program and /or the Medicaid home and community-based services waiver program for the aged and disabled as of January 1 , 1995 . Measures . Outcomes of needs met and client satisfaction were measured through telephone surveys every 6 months for 2 years . Results . A total of 1006 participants ( 45 % ) completed the 2-year evaluation study . For the group using only the NTP program , perception of needs met and client satisfaction were significantly better than the control group over the 2 years . During this period , the group using only the CFS program had significantly better client satisfaction than the control group . However , the effect sizes of the significant differences were small , and no statistically significant effects were found for the group using both programs . Conclusions . Client-centered quality improvement strategies can be implemented to enable public CBLTC programs to meet client needs better and increase client satisfaction Purpose : In developing our Patient-Centered Team CareSM ( PCTC ) program , we design ed a Plan-of-Care ( POC ) tool to facilitate the physician-patient discussion for setting health goals . This study aim ed to determine the effectiveness of the POC tool in improving clinical outcomes . Methods : We compared baseline and 6-month or greater follow-up values for hemoglobin A1c ( HbA1c ) , low-density lipoprotein ( LDL ) , systolic blood pressure ( SP ) , diastolic blood pressure ( DP ) , and weight for PCTC patients ( intervention group ) and non-PCTC patients ( control group ) . For the intervention group , we also compared POC tool completeness scores ( 1 , low and 8 , high ) . Results : Of 1366 patients , 1110 ( 593 intervention , 517 control ) had baseline and follow-up clinical measures for analysis . After adjusting for demographics , significant effects occurred in the intervention group for HbA1c ( P = .0067 ) , LDL ( P = .012 ) , and DP ( P = .091 ) . For completeness of POC , a significant association occurred between more fully completed forms ( scores , 5 - 8 ) and change in HbA1c ( P < .001 ) and SP ( P = .011 ) . Conclusion : Patients receiving a POC showed significant improvement in 3 of 5 clinical outcomes compared with those without the tool , and those with more fully completed forms had significant improvement in 2 of 5 clinical outcomes compared with those with partially completed forms OBJECTIVE Although doctor-patient communication has been the focus of numerous studies , there is a lack of empirical evidence on which to base a curriculum for teaching effective communication skills for use in an oncology setting . Research within the general practice area identifies patient-centred and doctor-centred behaviours as the most important dimensions of doctor-patient communication . This study examined patients and their relatives/friends ' preferences for and satisfaction with patient-centred and doctor-centred consulting styles . It was argued that by determining patient preferences for consulting styles , specific recommendations for improving communication in the oncology setting could be formulated . PARTICIPANTS AND METHODS One hundred and thirteen women who had been treated for breast cancer and 48 of their relatives or friends watched videotaped scenarios of an oncology consultation , using professional actors . Viewers were r and omly allocated to either a good prognosis or poor prognosis video , in which the oncologist discussed the patient 's diagnosis , treatment and prognosis . These segments were presented in both styles to allow viewers to directly compare and contrast the patient-centred and doctor-centred approach . Outcomes included style preference and satisfaction . Demographic details , information and involvement preferences , anxiety and depression levels were also obtained . RESULTS Both patients and their relatives or friends significantly preferred a patient-centred consulting style across all aspects of the consultation ( p<0.0001 ) , except within the treatment segment of the good prognosis video where there was no significant difference . One third of the viewers preferred a doctor-centred style for the treatment and prognosis segments . Predictors of a patient-centred style preference in the treatment and prognosis segments included watching a poor prognosis video ( OR=2.45 , 95 % CI 1.04 - 5.81 , p=0.04 ; OR=3.22 , 95 % CI 1.22 - 8.50 , p=0.02 , respectively ) , and being employed in a professional occupation ( OR=2.38 , 95 % CI 1.02 - 5.53 , p=0.04 for the treatment segment only ) . Satisfaction ratings varied within and across videos . CONCLUSION Despite some method ological limitations , this study provides empirical data indicating that patients and their relatives or friends prefer a patient-centred approach to the consultation , particularly when the patient has a poor prognosis . The fact that a substantial minority of patients preferred a doctor-centred style emphasizes the need to enhance physicians ' abilities to recognize different patient needs throughout the consultation |
12,885 | 20,561,461 | The systematic review showed that SBSHS are not associated with higher rates of sexual activity among young people , nor with an earlier age of first intercourse .
There was evidence to show positive effects in terms of reductions in births to teenage mothers , and in chlamydial infection rates among young men , although this evidence coming primarily from the USA .
Also evidence to suggest that broad-based , holistic service models , not restricted to sexual health , offer the strongest basis for protecting young people 's privacy and confidentiality , countering perceived stigmatisation , offering the most comprehensive range of products and services , and maximising service uptake .
Findings from the mapping study also indicate that broad-based services , which include medical practitioner input within a multiprofessional team , meet the stated preferences of staff and of young people most clearly .
Partnership-based developments of this kind also conform to the broad policy principles embodied in the Every Child Matters framework in the UK and allied policy initiatives .
Also , the distinction made in the question naire between ' general health ' and ' sexual health ' services did not prove robust .
There is no single , dominant service model in the UK . | BACKGROUND Report based on a service-mapping study and a systematic review concerning sexual health services for young people , either based in or closely linked to schools .
OBJECTIVES To identify current forms of school-based sexual health services ( SBSHS ) and school-linked sexual health services ( SLSHS ) in the UK , review and synthesis e existing evidence from qualitative and quantitative studies concerning the effectiveness , acceptability and cost-effectiveness of these types of service and to identify potential areas for further research . | Systematic Review Series Series Editors : Cynthia Mulrow , MD , MSc Deborah Cook , MD , MSc The last article in this series outlined methods with which to search the literature for studies on the clinical question that generates a systematic review [ 1 ] . Herein , we discuss the subsequent steps of selecting and appraising studies for a review . Both of these steps involve important judgments that can influence the results of a review . In selecting studies , review ers judge the relevance of the studies to the review question . In appraising studies , review ers judge numerous features of design and analysis . Some of these judgments are easy to make ; others are more difficult and prone to error . To be confident in their decisions , review ers should use methods that are reliable ( the results do not change if the procedure is repeated ) , impartial ( not influenced by the study results ) , and explicit ( unambiguous ) [ 2 ] . These strategies for selection and appraisal are sensible , and they distinguish most systematic review s from most narrative review s. However , evidence to support the importance of some of the methods we suggest is either scant or conflicting ; readers are referred to the original research on these approaches for more details . Selecting Studies for Systematic Review s If review ers perform a comprehensive search of the literature using the methods described previously in this series [ 1 ] , they will probably have assembled a large sample of articles . This sample will include most ( ideally , all ) studies that are relevant to the review question ( that is , the sensitivity of the search will be high ) . Inevitably , because such a wide net is cast , articles not pertinent to the clinical question will be retrieved ( that is , the specificity of the search will be modest ) . Thus , the review ers ' next task is to sort through all of the potentially relevant articles and select those that will be included in the review . To do so , review ers adopt several of the tactics listed in Table 1 and Table 2 for planning and executing the selection process ( in effect , improving the specificity of the search ) ; these tactics are described below . Table 1 . Planning Study Selection Table 2 . Strategies for Selecting and Appraising Studies Begin with a Well-Built Clinical Question Review ers should ensure that the question for review includes the four elements of a well-built clinical question [ 3 , 4 ] : the patients of interest , the main interventions under investigation , the comparison interventions , and the clinical outcomes of interest . By including these four elements , review ers can better focus the selection process . Choose Selection Criteria That Fit the Clinical Question Consider a systematic review of the effectiveness of a drug treatment ( for example , a proton-pump inhibitor ) for patients with a particular disorder ( such as esophageal reflux ) . Review ers need to decide whether to include studies of patients with any symptoms of reflux , only those with classic symptoms , or only those in whom definitive diagnostic tests have confirmed the presence of reflux . In addition , review ers might choose to include studies of patients with different comorbid conditions ; patients from different demographic or geographic or cultural background s ; or patients from different health systems , such as inpatient or community population s. Similarly , review ers should use selection criteria that reflect the main and comparison interventions of interest . In our esophageal reflux example , review ers would need to decide whether to include studies of a particular drug or studies of all agents in that drug 's class and whether to include studies of any dose and regimen or only studies with a specific regimen . For the comparison interventions , the review ers would decide whether to include studies that compare the experimental drug with alternate treatments ( such as antacids or histamine-2-receptor antagonists ) , with placebo , or with both . For the clinical outcomes , review ers have analogous tasks of defining the outcomes and translating them into criteria . In our example , the review ers would start by listing each clinical outcome ( for example , whether the outcome was endoscopic or clinical and whether it focused on cure or persistence ) and then decide whether to include studies that reported any outcome or only those with certain clinical ly important outcomes ( such as improvement in symptoms at 1 year ) . After thoroughly considering each element of the review question , review ers compile a set of explicit selection criteria . When these criteria are not explicit , the results of the review are more prone to error [ 5 , 6 ] . Reporting the selection criteria used in a review is extremely important to readers because the criteria indicate the relevance of the review to the readers ' clinical practice . Specify the Types of Study Design To Be Included After creating selection criteria that appropriately reflect the review question , review ers should consider which study design s to include . Ideally , review ers choose study design s that are most likely to produce valid results . For example , to answer questions about therapy or harm , review ers may want to include r and omized trials [ 7 ] because they provide more accurate estimates of benefit or harm than do cohort studies , casecontrol studies , and case series [ 8 ] . In reality , however , r and omized trials may not be conducted to address questions of harm [ 9 ] . Therefore , review ers need to consider which study design s are likely to be available to answer their question ; this information may necessitate modification of originally conceptualized selection criteria to incorporate observational ( nonexperimental ) studies . Specify Criteria Related to Type and Form of Publication Review ers also need to consider issues related to type and form of publication . Ideally , all of the relevant studies would be published as peer- review ed journal articles . However , some completed studies may be published only as abstract s , in non-peer- review ed form , or not at all . Review ers decide whether to include these incompletely reported studies when planning their literature search . By including all articles in various stages of publication and subjecting them to rigorous critical appraisal , review ers minimize the threat of publication bias ( the preferential reporting of studies with positive results ) [ 10 - 12 ] , which could generate misleading review s. Other studies may be reported more than once . To avoid over-representing duplicate studies in the review , investigators should plan to look for and exclude duplicate publications [ 13 ] . Finally , because studies may be published in different language s and because excluding studies published in different language s may bias the results of review s [ 14 , 15 ] , articles should be included , as appropriate , regardless of the language of publication ( translating as necessary ) . Limited time and re sources , however , may preclude such an approach . Construct and Pretest Selection Forms After deciding on selection criteria , review ers can prepare customized forms that contain checklists of the selection criteria ( Figure 1 ) . Using these forms can simplify the selection process , increase reliability , and provide a record of the judgments made about each study . After drafting form prototypes , review ers pretest these forms for clarity , ease of application , and reliability . To pretest the forms , two or more independent review ers typically apply them to a r and om sample of studies identified by the literature search . Review ers compare their results to identify sources of ambiguity and then revise the forms accordingly . If the revisions are substantial , this process may need to be repeated before the forms can be used . Figure 1 . Example of a form that might be developed for the selection of studies for a systematic review evaluating the efficacy of -blockers for secondary prevention of variceal bleeding . Write a Detailed Protocol Having a selection protocol as part of a larger protocol for the entire review helps review ers in two ways . First , it provides a document that explicitly states the review question and the selection criteria , making the process accountable . Review ers can later return to the protocol for guidance in resolving disagreements about article selection . Second , the selection protocol identifies what work will be done , by whom , in what manner , when , and for what reason ; thus , it provides a mode of communication within the review team . When review ers have a very large sample of studies from which to select , they can simplify this task by review ing all of the titles , then the abstract s , and then the full articles , excluding studies that do not meet one or more selection criteria at each step . In doing so , review ers should record ( on the selection forms ) the reasons for exclusion . After review ers have selected studies for the systematic review , they will move to the next task of critical appraisal . This procedure also requires careful planning . Appraising Studies for Systematic Review s Review ers appraise the studies selected for review with three objectives in mind : 1 ) to underst and the validity of the studies , 2 ) to uncover reasons for differences among study results other than chance , and 3 ) to provide readers with sufficient information with which to judge for themselves the applicability of the systematic review to their clinical practice . To achieve these goals , review ers use the strategies outlined in Table 2 and Table 3 to carefully reexamine many important features of the primary studies . Table 3 . Planning Study Appraisal Examine Important Clinical Features Although the selection criteria for a systematic review define the population , interventions , and outcomes of interest , the appraisal process involves a detailed assessment of the patients ( for example , high , medium , or low risk ) , the study interventions ( for example , frequency , degree , and duration ) , and the outcome measurements ( for example , definitions and degree of surveillance ) PURPOSE The purpose of this investigation was to assess the School-Based Adolescent Health Care Program , which provided comprehensive health-related services in 24 school-based health centers . METHODS The outcomes evaluation compared a cohort of students attending 19 participating schools and a national sample of urban youths , using logit models to control for observed differences between the two groups of youths . Outcome measures included self-reports concerning health center utilization , use of other health care providers , knowledge of key health facts , substance use , sexual activity , contraceptive use , pregnancies and births , and health status . RESULTS The health centers increased students ' access to health care and improved their health knowledge . However , the estimated impacts on health status and risky behaviors were inconsistent , and most were small and not statistically significant . CONCLUSIONS School-based health centers can increase students ' health knowledge and access to health-related services , but more intensive or different services are needed if they are to significantly reduce risk-taking behaviors Although millions of couples rely on male latex condoms to protect against unintended pregnancy and sexually transmitted infections , their use is limited in part by questions about their performance . Rates of condom breakage and slippage , two measures of performance , vary broadly across studies . This variation in part reflects study variability and limitations , including sample size , reliance on subjects ' memory , user population s , and products evaluated . In an effort to define condom performance in a group of monogamous couples typical of those using condoms for contraception , we conducted a clinical trial of a single br and of lubricated condoms ( Durex Ramses ) . A total of 4637 attempts to use the condom were evaluated . Six breaks occurred before intercourse ( non clinical breaks ) , and 10 condoms broke during intercourse or were only noted to have broken upon withdrawal ( clinical breaks ) , result ing in a non clinical breakage rate of 0.13 % ( 95 % confidence interval , 0.05 - 0.28 % ) , clinical breakage rate of 0.28 % ( 0.15 - 0.48 % ) , and a total breakage rate of 0.41 % ( 0.25 - 0.64 % ) . The rate of complete slippage was 0.63 % ( 0.42 - 0.90 % ) , and total failure ( clinical breaks plus complete slips ) was 1.04 % ( 0.76 - 1.37 % ) . These rates are lower than those in other studies with the exception of one , a prospect i ve investigation in a population of female prostitutes . Results indicate that condoms can , in experienced , motivated population s , provide excellent performance and suggest that their efficacy at preventing pregnancy may equal that of the most reliable forms of contraception . Because this study involved a single condom br and , these results may not be generalizable to other br and Abstract Objective : To assess the effectiveness of a teacher led intervention to improve teenagers ' knowledge about emergency contraception . Design : Cluster r and omised controlled trial . Setting : 24 mixed sex , state secondary schools in Avon , south west Engl and . Participants : 1974 boys and 1820 girls in year 10 ( 14 - 15 year olds ) . Intervention : Teachers gave a single lesson on emergency contraception to year 10 pupils . The teachers had previously received in-service training on giving the lesson . The pupils were actively involved during the lesson . Main outcome measures : Question naires distributed to pupils at baseline and six months after the intervention assessed their knowledge of the correct time limits for hormonal emergency contraception and for use of the intrauterine device as emergency contraception , the proportion of pupils who were not virgins , the proportion who had used emergency contraception , and the pupils ' intention to use emergency contraception in the future . Results : The proportion of pupils knowing the correct time limits for both types of emergency contraception was significantly higher in the intervention group than in the control group at six months ' follow up ( hormonal contraception : proportion of boys 15.9 % higher ( 95 % confidence interval 6.5 % to 25.3 % ) , girls 20.4 % ( 10.4 % to 30.4 % ) ; intrauterine device used as emergency contraception : boys 4.2 % ( 0.7 % to 7.7 % ) , girls 10.7 % ( 0.4 % to 21.0 % ) . The number of pupils needed to be taught for one more pupil to know the correct time limits was six for boys and five for girls . The intervention and control groups did not differ in the proportion of pupils who were not virgins , in the proportion who had used emergency contraception , and in the proportion intending to use emergency contraception in the future . Conclusions : The intervention significantly improved the proportion of boys and girls knowing the correct time limits for both types of emergency contraception . The intervention did not change the pupils ' sexual activity or use of emergency contraception . What is already known on this topic Use of condoms as a sole method of contraception is increasing Emergency contraception — either hormonal or the intrauterine device used as emergency contraception — can be used when condoms or other methods fail or are not used Awareness of emergency contraception in school pupils is high , but knowledge of specific details , such as the time period within which it can be used , is poor What this study adds A single lesson on emergency contraception given by teachers who had previously been trained improves the proportion of pupils aware of the correct time limits for use of both types of emergency contraception Such a lesson does not increase sexual activity or use of emergency There has been an increasing interest in using expected value of information ( EVI ) theory in medical decision making , to identify the need for further research to reduce uncertainty in decision and as a tool for sensitivity analysis . Expected value of sample information ( EVSI ) has been proposed for determination of optimum sample size and allocation rates in r and omized clinical trials . This article derives simple Monte Carlo , or nested Monte Carlo , methods that extend the use of EVSI calculations to medical decision applications with multiple sources of uncertainty , with particular attention to the form in which epidemiological data and research findings are structured . In particular , information on key decision parameters such as treatment efficacy are invariably available on measures of relative efficacy such as risk differences or odds ratios , but not on model parameters themselves . In addition , estimates of model parameters and of relative effect measures in the literature may be heterogeneous , reflecting additional sources of variation besides statistical sampling error . The authors describe Monte Carlo procedures for calculating EVSI for probability , rate , or continuous variable parameters in multi parameter decision models and approximate methods for relative measures such as risk differences , odds ratios , risk ratios , and hazard ratios . Where prior evidence is based on a r and om effects meta- analysis , the authors describe different ESVI calculations , one relevant for decisions concerning a specific patient group and the other for decisions concerning the entire population of patient groups . They also consider EVSI methods for new studies intended to up date information on both baseline treatment efficacy and the relative efficacy of 2 treatments . Although there are restrictions regarding models with prior correlation between parameters , these methods can be applied to the majority of probabilistic decision models . Illustrative worked examples of EVSI calculations are given in an appendix OBJECTIVE To examine the relationship between adolescents ' perception of the confidentiality of care provided by their regular health care provider and their reported use of this provider for private health information and for pelvic examinations . DESIGN Anonymous , self-report survey . SETTING Thirty-two r and omly selected public high schools in Massachusetts . PARTICIPANTS Of 2224 students in systematic ally selected 9th and 12th grade classrooms , 1715 ( 50 % male ) had a regular provider and a checkup within the last year . RESULTS Of teens surveyed , 76 % wanted the ability to obtain confidential health care , but only 45 % perceived their regular provider to provide this , and only 28 % had discussed it explicitly . Logistic regression analyses revealed strong relationships between confidentiality and all outcomes studied . Among adolescents , the likelihood of having discussed sexually transmitted diseases , pregnancy prevention , and /or facts about sex with their provider was greater among teens who received a confidentiality assurance than that for teens who did not ( odds ratio [ OR ] = 2.7 ; 95 % confidence interval [ CI ] , 2.2 - 3.4 ) . A similar relationship for teens ' likelihood of having discussed substance use with the provider was found ( OR = 1.8 ; 95 % CI , 1.4 - 2.3 ) . Among sexually active females , the likelihood of a recent pelvic examination for those who received a confidentiality assurance was greater than for those who did not ( OR = 3.3 ; 95 % CI , 2.1 - 5.5 ) . CONCLUSIONS This study furthers evidence of an important link between teens ' perception of confidentiality and use of health care services and information . Because teens ' health risks lie largely in potential risks from health-related behaviors , confidentiality in health care may be a critical factor in disclosure and discussion of risky behaviors , and ultimately in appropriate use of health care services . Efforts should be made to increase teens ' access to confidential health care sources OBJECTIVE To identify the extent to which family physicians support school-based education programs regarding the human immunodeficiency virus ( HIV ) . Sexually active adolescents are at risk for infection with HIV . Education programs on HIV that target this vulnerable group effectively prevent infection , yet family physicians are often not directly involved in the design and implementation of such programs . DESIGN A systematic r and om sample of 2660 members of the American Academy of Family Physicians was surveyed using a mailed question naire to assess clinical experiences with HIV disease , willingness to provide HIV treatment , and support for school-based HIV education programs . The response rate was 63.7 % . Poststratification weights were applied to adjust for the slight under-representation of non-board-certified physicians in the study sample . RESULTS Support for school-based HIV counseling programs was overwhelmingly positive . The mean level of support was 1.28 ( with 1 indicating strong approval and 4 strong disapproval ) . Physicians ' attitudes toward programs that include condom availability were marginally less favorable ( 1.92 ) . Residency trained ( P = .009 ) and female physicians ( P = .010 ) expressed the greatest support for school-based programs . Physicians with fewer professional concerns about providing direct HIV patient care ( P = .030 ) and who believed that communication with their patients about sexuality was an acceptable component of clinical care ( P < .001 ) were most likely to support school-based programs . CONCLUSIONS Family physicians can play an important role in design ing and implementing HIV education programs . The results of these analyses suggest family physicians may be relied on to endorse school-based HIV prevention programs , including programs that make condoms available to adolescents . School and public health authorities should enlist family physicians ' assistance when planning and implementing these or related community-based HIV education activities Objective : The impact of a multicomponent intervention programme on the sexual health of adolescents was assessed in rural Tanzania . Design : A community-r and omized trial . Methods : Twenty communities were r and omly allocated to receive either a specially design ed programme of interventions ( intervention group ) or st and ard activities ( comparison group ) . The intervention had four components : community activities ; teacher-led , peer-assisted sexual health education in years 5–7 of primary school ; training and supervision of health workers to provide ‘ youth-friendly ’ sexual health services ; and peer condom social marketing . Impacts on HIV incidence , herpes simplex virus 2 ( HSV2 ) and other sexual health outcomes were evaluated over approximately 3 years in 9645 adolescents recruited in late 1998 before entering years 5 , 6 or 7 of primary school . Results : The intervention had a significant impact on knowledge and reported attitudes , reported sexually transmitted infection symptoms , and several behavioural outcomes . Only five HIV seroconversions occurred in boys , whereas in girls the adjusted rate ratio ( intervention versus comparison ) was 0.75 [ 95 % confidence interval ( CI ) 0.34 , 1.66 ] . Overall HSV2 prevalences at follow-up were 11.9 % in male and 21.1 % in female participants , with adjusted prevalence ratios of 0.92 ( CI 0.69 , 1.22 ) and 1.05 ( CI 0.83 , 1.32 ) , respectively . There was no consistent beneficial or adverse impact on other biological outcomes . The beneficial impact on knowledge and reported attitudes was confirmed by results of a school examination in a separate group of students in mid-2002 . Conclusion : The intervention substantially improved knowledge , reported attitudes and some reported sexual behaviours , especially in boys , but had no consistent impact on biological outcomes within the 3-year trial period OBJECTIVES This study examines the impact of the condom availability program in New York City public high schools by comparing rates of sexual activity and condom use for New York students and similar students in Chicago . METHODS A total of 7119 students from 12 r and omly selected New York schools and 5738 students from 10 Chicago schools participated in a cross-sectional survey . RESULTS New York students , compared with Chicago students , reported equal rates of sexual activity but higher rates of condom use at last intercourse ( odds ratio [ OR ] = 1.36 ) . For higher-risk students ( those with three or more sexual partners in the past 6 months ) , condom use was greater in New York ( OR = 1.85 ) than in Chicago . CONCLUSIONS Condom availability has a modest but significant effect on condom use and does not increase rates of sexual activity . These findings suggest that school-based condom availability can lower the risk of HIV and other sexually transmitted diseases for urban teenagers in the United States OBJECTIVES To determine the relative efficacy and cost-effectiveness of five of the most commonly used antimicrobial preparations for treating mild to moderate facial acne in the community ; the propensity of each regimen to give rise to local and systemic adverse events ; whether pre-existing bacterial resistance to the prescribed antibiotic result ed in reduced efficacy ; and whether some antimicrobial regimens were less likely to give rise to resistant propionibacterial strains . DESIGN This was a parallel group r and omised assessor-blind controlled clinical trial . It was a pragmatic design with intention-to-treat analysis . All treatments were given for 18 weeks , after a 4-week treatment free period . Outcomes were measured at 0 , 6 , 12 and 18 weeks . SETTING Primary care practice s and colleges in and around Nottingham and Leeds , and one practice in Stockton-on-Tees , Engl and . PARTICIPANTS Participants were 649 people aged 12 - -39 years , all with mild to moderate inflammatory acne of the face . INTERVENTIONS Study participants were r and omised into one of five groups : 500 mg oral oxytetracycline ( non-proprietary ) twice daily ( b.d . ) + topical vehicle control b.d . ; 100 mg oral Minocin MR ( minocycline ) once daily ( o.d . ) + topical vehicle control b.d . ; topical Benzamycin ( 3 % erythromycin + 5 % benzoyl peroxide ) b.d . + oral placebo o.d . ; topical Stiemycin ( 2 % erythromycin ) o.d . + topical Panoxyl Aquagel ( 5 % benzoyl peroxide ) o.d . + oral placebo o.d . , and topical Panoxyl Aquagel ( 5 % benzoyl peroxide ) b.d . + oral placebo o.d . ( the active comparator group ) . MAIN OUTCOME MEASURES The two primary outcome measures were : ( 1 ) the proportion of patients with at least moderate self-assessed improvement as recorded on a six-point Likert scale , and ( 2 ) change in inflamed lesion count ( red spots ) . RESULTS The best response rates were seen with two of the topical regimens ( erythromycin plus benzoyl peroxide administered separately o.d . or in a combined proprietary formulation b.d . ) , compared with benzoyl peroxide alone , oxytetracycline ( 500 mg b.d . ) and minocycline ( 100 mg o.d . ) , although differences were small . The percentage of participants with at least moderate improvement was 53.8 % for minocycline ( the least effective ) and 66.1 % for the combined erythromycin/benzoyl peroxide formulation ( the most effective ) ; the adjusted odds ratio for these two treatments was 1.74 [ 95 % confidence interval ( CI ) 1.04 to 2.90 ] . Similar efficacy rankings were obtained using lesion counts , acne severity scores and global rating by assessor . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective regimen ( ratio of means 12.3 ; difference in means -0.051 units/GBP , 95 % CI -0.063 to -0.039 ) . The efficacy of oxytetracycline was similar to that of minocycline , but at approximately one-seventh of the cost . For all regimens , the largest reductions in acne severity were recorded in the first 6 weeks . Reductions in disability scores using the Dermatology Quality of Life Scales were largest for both topical erythromycin-containing regimens and minocycline . The two topical erythromycin-containing regimens produced the largest reductions in the prevalence and population density of cutaneous propionibacteria , including antibiotic-resistant variants , and these were equally effective in participants with and without erythromycin-resistant propionibacteria . The clinical efficacy of both tetracyclines was compromised in participants colonised by tetracycline-resistant propionibacteria . None of the regimens promoted an overall increase in the prevalence of antibiotic-resistant strains . Systemic adverse events were more common with the two oral antibiotics . Local irritation was more common with the topical treatments , particularly benzoyl peroxide . Residual acne was present in most participants ( 95 % ) at the end of the study . CONCLUSIONS The response of mild to moderate inflammatory acne to antimicrobial treatment in the community is not optimal . Only around half to two-thirds of trial participants reported at least a moderate improvement over an 18-week study period ; extending treatment beyond 12 weeks increased overall benefit slightly . Around one-quarter dropped out when using such treatments , and 55 % sought further treatment after 18 weeks . Topical antimicrobial therapies performed at least as well as oral antibiotics in terms of clinical efficacy . Benzoyl peroxide was the most cost-effective and minocycline the least cost-effective therapy for facial acne . The efficacy of all three topical regimens was not compromised by pre-existing propionibacterial resistance . Benzoyl peroxide was associated with a greater frequency and severity of local irritant reactions . It is suggested that the use of a combination of topical benzoyl peroxide and erythromycin gives less irritation and better quality of life . There was little difference between erythromycin plus benzoyl peroxide administered separately and the combined proprietary formulation in terms of efficacy or local irritation , except that the former was nearly three times more cost-effective . The data on cost-effectiveness , and outcomes in patients with resistant propionibacterial floras , did not support the first line use of minocycline for mild to moderate inflammatory acne of the face . Three priority areas for clinical research in acne are : defining end-points in acne trials ( i.e. what is a satisfactory outcome ? ) ; developing and validating better patient-based measures for assessing treatment effects on facial and truncal acne ; and exploring patient characteristics that may modify treatment effects ( efficacy and tolerability ) In 1991 , the New York City Board of Education exp and ed HIV/AIDS education to include condom availability in every public high school . The evaluation was design ed to examine the impact of the program on students and monitor changes in parent 's knowledge , attitudes , and beliefs . Findings are reported from the first wave of data from the parent survey , 716 parents from 12 r and omly chosen NYC high schools and 81 parents from 12 focus groups held at six of the schools . Sixty-nine percent of parents believed students should be able to receive condoms at school , although nearly half felt they should have the right to keep their children from doing so . Most believed making condoms available would result in safer sex practice s among students who were sexually active . Data suggest parents support the school 's role in reducing HIV/AIDS transmission among adolescents and believe making condoms available represents an acceptable component of an HIV/AIDS prevention program In 1991 , the New York City Board of Education exp and ed HIV/AIDS education to include condom availability in public high schools . A three-year study was initiated to assess the program 's impact on student risk behavior , the schools ' social environments , and patterns of communication about HIV/AIDS and condoms among students , their parents and teachers in 12 r and omly selected New York City high schools . Findings on gender differences in both attitudes and use of the program among sexually active students are reported here . Sexually active girls ' attitudes toward using condoms and the condom availability program were more positive than those of sexually active boys , yet boys were more likely to have used the program . Girls reported embarrassment and confidentiality concerns as the main deterrents to using the program . Data suggest that schools need to examine the address gender-specific attitudes that contribute to reluctance to use the program among sexually active girls The issue of the efficient allocation of research funds has been addressed using various quantitative methods . Bayesian value of information ( VoI ) analysis provides an explicit and comprehensive analytic process for the comparison of alternative sources of research . This paper presents an adapted non-parametric application of a VoI analysis of prospect i ve trials comparing alternative adjuvant therapies for postmenopausal women with node positive early breast cancer . The results show that such trials would produce substantial net benefits , though the extent of the net benefits is clearly influenced by the assumed length of usefulness of the research . The application of the VoI methodology shows that such analyses are practical and the recent increase in the use of stochastic decision models in the economic evaluation of health care technologies facilitates further applications of VoI analyses to inform the allocation of research funds |
12,886 | 30,917,819 | Studies that find that working time is detrimental to employee health , generally also find detrimental results for patient safety .
This is particularly shown through increases in errors by health personnel .
When controlling for employee health , the relationship between working time arrangements and patient safety is reduced , but still significant .
Conclusions Results suggest that employee health partially ( but not completely ) mediates the relationship between working time arrangements and patient safety .
However , there is a lack of studies directly investigating employee health as a mediator between working time arrangements and patient safety . | Background A number of working time arrangements have been linked to negative consequences for both health personnel and their patients .
A common hypothesis put forth to explain these findings suggests that certain working time arrangements lead to negative patient consequences due to the adverse impact they have on employee health .
The purpose of this study is to use systematic review s to investigate whether employee health explains the relationship between working time arrangements and patient safety . | This study surveyed Certified Registered Nurse Anesthetist ( CRNA ) members of the American Association of Nurse Anesthetists ( AANA ) on their frequency of call-shift fatigue , fatigue symptoms , medical errors associated with fatigue , and use of fatigue counter measures and avoidance strategies . A secondary aim was to identify predictors of call-shift fatigue . An invitation to complete an anonymous electronic survey was sent to 2,500 r and omly selected AANA members . Data were collected on CRNAs ' fatigue experience , call-shift length and frequency , errors in patient care , and use of fatigue counter measures and avoidance strategies . Analysis included descriptive and inferential statistics . Logistic regression was used to identify predictors of call-shift fatigue . Of 325 CRNAs who provided data , 82 % reported experiencing call-shift fatigue , 87 % used fatigue counter measures , 77 % used fatigue-avoidance strategies , and 28 % reported committing a medical error because of fatigue . Predictors included hours to recovery from a call shift ( odds ratio [ OR ] = 1.08 , 95 % confidence interval [ CI ] = 1.04 - 1.12 ) , working 5 to 6 calls per month ( OR = 3.78 , CI = 1.17 - 12.23 ) , working 7 or more calls per month ( OR = 4.87 , CI = 1.93 - 12.33 ) , use of fatigue counter measures ( OR = 5.44 , CI = 2.15 - 13.77 ) , and fatigue symptoms ( OR = 2.19 , CI = 1.03 - 4.67 ) . Call-shift fatigue is a common problem among CRNAs and is associated with medical errors and negative health consequences Study Objectives While short and poor quality sleep among training physicians has long been recognized as problematic , the longitudinal relationships among sleep , work hours , mood , and work performance are not well understood . Here , we prospect ively characterize the risk of depression and medical errors based on preinternship sleep disturbance , internship-related sleep duration , and duty hours . Methods Survey data from 1215 nondepressed interns were collected at preinternship baseline , then 3 and 6 months into internship . We examined how preinternship sleep quality and internship sleep and work hours affected risk of depression at 3 months , per the Patient Health Question naire 9 . We then examined the impact of sleep loss and work hours on depression persistence from 3 to 6 months . Finally , we compared self-reported errors among interns based on nightly sleep duration ( ≤6 hr vs. > 6 hr ) , weekly work hours ( < 70 hr vs. ≥70 hr ) , and depression ( non- vs. acutely vs. chronically depressed ) . Results Poorly sleeping trainees obtained less sleep and were at elevated risk of depression in the first months of internship . Short sleep ( ≤6 hr nightly ) during internship mediated the relationship between sleep disturbance and depression risk , and sleep loss led to a chronic course for depression . Depression rates were highest among interns with both sleep disturbance and short sleep . Elevated medical error rates were reported by physicians sleeping ≤6 hr per night , working ≥ 70 weekly hours , and who were acutely or chronically depressed . Conclusions Sleep disturbance and internship-enforced short sleep increase risk of depression development and chronicity and medical errors . Interventions targeting sleep problems prior to and during residency hold promise for curbing depression rates and improving patient care BACKGROUND Sleep deprivation has been associated with an increased incidence of medical errors and can jeopardise patients ' safety during medical crisis management . The aim of the study was to assess the effect of sleep deprivation on the management of simulated anaesthesia crisis by residents in anaesthesiology . METHODS A r and omised , comparative , monocentric crossover study involving 48 residents in anaesthesia was performed on a high fidelity patient simulator . Each resident was evaluated in a sleep-deprived state ( deprived group , after a night shift duty ) and control state ( control group , after a night of sleep ) . Performance was assessed through points obtained during crisis scenario 1 ( oesophageal intubation followed by anaphylactic shock ) and scenario 2 ( anaesthesia-related bronchospasm followed by ventricular tachycardia ) . Sleep periods were recorded by actigraphy . Two independent observers assessed the performances . The primary endpoint of the study was the score obtained for each scenario . RESULTS Resident 's crisis management performance is associated with sleep deprivation ( scenario 1 : control=39 [ 33 - 42 ] points vs. deprived=26 [ 19 - 40 ] points , P=0.02 ; scenario 2 : control=21 [ 17 - 24 ] vs. deprived=14 [ 12 - 19 ] , P=0.01 ) . The main errors observed were : error in drug administration and dose , delay in identification of hypotension , and missing communication with the surgical team about situation . CONCLUSIONS The present study showed that sleep deprivation is associated with impairment of performance to manage crisis situations by residents in anaesthesia CONTEXT Better hospital nurse staffing , more educated nurses , and improved nurse work environments have been shown to be associated with lower hospital mortality . Little is known about whether and under what conditions each type of investment works better to improve outcomes . OBJECTIVE To determine the conditions under which the impact of hospital nurse staffing , nurse education , and work environment are associated with patient outcomes . DESIGN , SETTING , AND PARTICIPANTS Outcomes of 665 hospitals in 4 large states were studied through linked data from hospital discharge abstract s for 1,262,120 general , orthopedic , and vascular surgery patients , a r and om sample of 39,038 hospital staff nurses , and American Hospital Association data . MAIN OUTCOME MEASURES A 30-day inpatient mortality and failure-to-rescue . RESULTS The effect of decreasing workloads by 1 patient/nurse on deaths and failure-to-rescue is virtually nil in hospitals with poor work environments , but decreases the odds on both deaths and failures in hospitals with average environments by 4 % , and in hospitals with the best environments by 9 % and 10 % , respectively . The effect of 10 % more Bachelors of Science in Nursing Degree nurses decreases the odds on both outcomes in all hospitals , regardless of their work environment , by roughly 4 % . CONCLUSIONS Although the positive effect of increasing percentages of Bachelors of Science in Nursing Degree nurses is consistent across all hospitals , lowering the patient-to-nurse ratios markedly improves patient outcomes in hospitals with good work environments , slightly improves them in hospitals with average environments , and has no effect in hospitals with poor environments Background : Shorter resident duty periods are increasingly m and ated to improve patient safety and physician well-being . However , increases in continuity-related errors may counteract the purported benefits of reducing fatigue . We evaluated the effects of 3 resident schedules in the intensive care unit ( ICU ) on patient safety , resident well-being and continuity of care . Methods : Residents in 2 university-affiliated ICUs were r and omly assigned ( in 2-month rotation-blocks from January to June 2009 ) to in-house overnight schedules of 24 , 16 or 12 hours . The primary patient outcome was adverse events . The primary resident outcome was sleepiness , measured by the 7-point Stanford Sleepiness Scale . Secondary outcomes were patient deaths , preventable adverse events , and residents ’ physical symptoms and burnout . Continuity of care and perceptions of ICU staff were also assessed . Results : We evaluated 47 ( 96 % ) of 49 residents , all 971 admissions , 5894 patient-days and 452 staff surveys . We found no effect of schedule ( 24- , 16- or 12-h shifts ) on adverse events ( 81.3 , 76.3 and 78.2 events per 1000 patient-days , respectively ; p = 0.7 ) or on residents ’ sleepiness in the daytime ( mean rating 2.33 , 2.61 and 2.30 , respectively ; p = 0.3 ) or at night ( mean rating 3.06 , 2.73 and 2.42 , respectively ; p = 0.2 ) . Seven of 8 preventable adverse events occurred with the 12-hour schedule ( p = 0.1 ) . Mortality rates were similar for the 3 schedules . Residents ’ somatic symptoms were more severe and more frequent with the 24-hour schedule ( p = 0.04 ) ; however , burnout was similar across the groups . ICU staff rated residents ’ knowledge and decision-making worst with the 16-hour schedule . Interpretation : Our findings do not support the purported advantages of shorter duty schedules . They also highlight the trade-offs between residents ’ symptoms and multiple secondary measures of patient safety . Further delineation of this emerging signal is required before widespread system change . Trial registration : Clinical Trials.gov , no. NCT00679809 BACKGROUND To minimize the occurrence of adverse events among patients , critical care nurses must be alert to subtle changes in patients ' conditions , perform accurate clinical assessment s , and respond expediently . However , little is known about the effects of the nurses ' work hours on vigilance and patients ' safety . OBJECTIVES To describe the work patterns of critical care nurses , determine if an association exists between the occurrence of errors and the hours worked by the nurses , and explore whether these work hours have adverse effects on the nurses ' vigilance . METHODS Data were obtained from a r and om sample of critical care nurses in the United States . Nurses eligible for the study were mailed two 14-day logbooks to fill out . Information collected included the hours worked , the time of day worked , overtime hours , days off , and sleep-wake patterns . On days worked , the respondents completed all work-related questions and questions about difficulties in remaining awake while on duty . Space was provided for descriptions of any errors or near errors that might have occurred . On days off , the nurses completed only those questions about sleep-wake patterns , mood , and caffeine intake . RESULTS The 502 respondents consistently worked longer than scheduled and for extended periods . Longer work duration increased the risk of errors and near errors and decreased nurses ' vigilance . CONCLUSIONS The findings support the Institute of Medicine recommendations to minimize the use of 12-hour shifts and to limit nurses ' work hours to no more than 12 consecutive hours during a 24-hour period RATIONALE Around-the-clock intensivist presence in intensive care units ( ICUs ) has been promoted as necessary to optimize outcomes . Little data have addressed how it affects the multiple stakeholders in such care . OBJECTIVES To assess effects of around-the-clock intensivist presence on intensivists , patients , families , housestaff , and nurses . METHODS This 32-week , crossover pilot trial of two intensivist staffing models , performed in two Canadian ICUs , alternated 8-week blocks of two staffing models : the st and ard model , where one intensivist worked for 7 days , taking night call from home ; and the shift work model , where one intensivist worked 7 day shifts , while other intensivists remained in the ICU at night . MEASUREMENTS AND MAIN RESULTS Surveys scaled from 0 - 100 points assessed outcomes for 24 intensivists ( primary outcome : burnout ) ; 119 families ( satisfaction ) ; 74 nurses ( satisfaction with collaboration and communications , role conflict ) ; and 34 housestaff ( autonomy , supervision , and learning opportunities ) . Outcomes for 501 patients included mortality , length of stay , and re source use . Intensivists doing shift work experienced less burnout ( -6.9 points ; P = 0.04 ) . Adjusted hospital mortality ( odds ratio , 1.22 ; P = 0.44 ) , ICU length of stay ( -6 h ; P = 0.46 ) , and family satisfaction ( 0.9 points ; P = 0.79 ) did not differ between staffing models . Under shift work staffing , nurses reported more role conflict ( 9 points ; P < 0.001 ) , whereas nighttime housestaff reported less autonomy , more supervision , but no difference in learning opportunities . CONCLUSIONS Shiftwork staffing was better for intensivists and most were receptive once they had experienced it . Although there were no evident negative outcomes for patients or families , further evaluation is needed to clarify how around-the-clock intensivist staffing influences the various stakeholders in ICU care , given power considerations in this study . Clinical trial registered with www . clinical trials.gov ( NCT 01146691 ) Purpose . To secure data from residents regarding residency work hours and correlates . Method . A national , r and om sample of postgraduate year 1 ( PGY1 ) and year 2 ( PGY2 ) residents in the 1998 - 1999 training year was identified using the American Medical Association ’s Graduate Medical Education data base . Residents completed a five-page survey with 44 questions and 144 separate data elements relating to their residency experience . Results . Completed surveys were received from 3,604 of 5,616 ( 64.2 % ) residents contacted . PGY1 residents reported working an average of 83 hours a week versus 76.2 hours for PGY2 residents ( p < .0001 ) . Total work hours were significantly correlated with reported stress and hours of sleep per week . Residents averaging more than 80 work hours per week were more likely to be involved in a personal accident or injury , a serious conflict with other staff members , and making a significant medical error . Cluster analysis revealed four different types of residency experience : high intensity , moderate intensity , low intensity , and moonlighters , suggesting that residents may have some choice in selecting a residency experience suited to their particular personal and professional needs . Conclusion . Nearly half of PGY1 and one third of PGY2 residents reported working more than 80 hours per week . These extended hours are significantly correlated with a number of patient care and personal health variables . Given the variety of program and specialty requirements and dem and s , it seems unlikely that an arbitrary limit or a simple decrease in work hours will provide a satisfactory solution to many resident and patient care concerns BACKGROUND Implicit rationing of nursing care refers to the withdrawal of or failure to carry out necessary nursing care activities due to lack of re sources , in the literature also described as missed care , omitted care , or nursing care left undone . Under time constraints , nurses give priority to activities related to vital medical needs and the safety of the patient , leaving out documentation , rehabilitation , or emotional support of patients . In nursing homes , little is known about the occurrence of implicit rationing of nursing care and possible contributing factors . OBJECTIVES The purpose of this study was ( 1 ) to describe levels and patterns of self-reported implicit rationing of nursing care in Swiss nursing homes and ( 2 ) to explore the relationship between staffing level , turnover , and work environment factors and implicit rationing of nursing care . DESIGN Cross-sectional , multi-center sub- study of the Swiss Nursing Home Human Re sources Project ( SHURP ) . SETTING S Nursing homes from all three language regions of Switzerl and . PARTICIPANTS A r and om selection of 156 facilities with 402 units and 4307 direct care workers from all educational levels ( including 25 % registered nurses ) . METHODS We utilized data from established scales to measure implicit rationing of nursing care ( Basel Extent of Rationing of Nursing Care ) , perceptions of leadership ability and staffing re sources ( Practice Environment Scale of the Nursing Work Index ) , teamwork and safety climate ( Safety Attitudes Question naire ) , and work stressors ( Health Professions Stress Inventory ) . Staffing level and turnover at the unit level were measured with self-developed questions . Multilevel linear regression models were used to explore the proposed relationships . RESULTS Implicit rationing of nursing care does not occur frequently in Swiss nursing homes . Care workers ration support in activities of daily living , such as eating , drinking , elimination and mobilization less often than documentation of care and the social care of nursing homes residents . Statistically significant factors related to implicit rationing of care were the perception of lower staffing re sources , teamwork and safety climate , and higher work stressors . Unit staffing and turnover levels were not related to rationing activities . CONCLUSIONS Improving teamwork and reducing work stressors could possibly lead to less implicit rationing of nursing care . Further research on the relationship of implicit rationing of nursing care and resident and care worker outcomes in nursing homes is requested INTRODUCTION The emergency department ( ED ) is dem and ing and high risk . The impact of sleep quantity has been hypothesized to impact patient care . This study investigated the hypothesis that fatigue and impaired mentation , due to sleep disturbance and shortened overall sleeping hours , would lead to increased nursing errors . METHODS This is a prospect i ve observational study of 30 ED nurses using self-administered survey and sleep architecture measured by wrist actigraphy as predictors of self-reported error rates . An actigraphy device was worn prior to working a 12-hour shift and nurses completed the Pittsburgh Sleep Quality Index ( PSQI ) . Error rates were reported on a visual analog scale at the end of a 12-hour shift . RESULTS The PSQI responses indicated that 73.3 % of subjects had poor sleep quality . Lower sleep quality measured by actigraphy ( hours asleep/hours in bed ) was associated with higher self-perceived minor errors . Sleep quantity ( total hours slept ) was not associated with minor , moderate , nor severe errors . DISCUSSION Our study found that ED nurses ' sleep quality , immediately prior to a working 12-hour shift , is more predictive of error than sleep quantity . These results present evidence that a " good night 's sleep " prior to working a nursing shift in the ED is beneficial for reducing minor errors Shiftwork and work-hour limits for junior doctors are now well established in hospital work patterns . In order to ensure that trainees have adequate exposure to daytime elective surgical procedures , there is a tendency to have long shifts that include an after-hours component . However , long shifts can cause performance decrement due to time-on-task fatigue . In addition , shifts that encroach upon sleep time result in sleep loss . Using a high-fidelity patient simulation environment , we undertook a r and omised , controlled trial to examine fatigue effects . A within-subjects comparison was used to evaluate the effect of 15-hour day shifts on the performance of 12 anaesthesia registrars . Preoperative assessment , machine check and taskwork using 42 task categories were evaluated . In both conditions , there was failure to meet current guidelines for preoperative evaluation or machine check , and when fatigued there was a ‘ trend ’ ( P=0.06 ) to a reduction in the number of items in the machine check . With increase in time awake , there was an increase in time taken for explanation to the patient , an increase in mean duration of explanation to the patient , more time looking at the intravenous line or fluids when multi-tasking but less time adjusting the intravenous fluid . These effects are minor during routine uncomplicated induction of anaesthesia , but further investigation is needed to examine fatigue effects during non-routine circumstances OBJECTIVE The aim of the present study was to clarify the current work and sleep situations of physicians in Japan and to clarify the association between these situations and excessive daytime sleepiness as well as medical incidents . METHODS A self-administered question naire survey was conducted among the members of the Japan Medical Association in 2008 . The r and omly selected subjects comprised 3,000 male physicians and 1,500 female physicians . RESULTS Valid responses were obtained from 3,486 physicians ( 2,298 men and 1,188 women ) . Mean sleep duration was 6 h 36 min for men and 6 h 8 min for women . The prevalence of lack of rest due to sleep deprivation was 30.4 % among men and 36.6 % among women ; the prevalence of insomnia was 21.0 % and 18.1 % , respectively ; and the prevalence of EDS was 3.5 % . The adjusted odds ratio for EDS was high for physicians who reported short sleep duration , lack of rest due to sleep deprivation , and a high frequency of on-call/overnight work . Physicians who had experienced a medical incident within the previous one month accounted for 19.0 % of participants . The adjusted odds ratio for medical incidents was high for those subjected to long working hours , high frequency of on-call/overnight works , lack of rest due to sleep deprivation , and insomnia . CONCLUSION In order to facilitate optimal health management for physicians as well as securing medical safety , it is important to fully consider the work and sleep situations of physicians BACKGROUND The effects of inadequate sleep on clinical decisions may be important for patients in critical care units , who are often more vulnerable than patients in other units . Fatigued nurses are more likely than well-rested nurses to make faulty decisions that lead to decision regret , a negative cognitive emotion that occurs when the actual outcome differs from the desired or expected outcome . OBJECTIVES To examine the association between selected sleep variables , impairment due to fatigue , and clinical -decision self-efficacy and regret among critical care nurses . Decision regret was the primary outcome variable . Methods A nonexperimental , descriptive design and extant measures were used to obtain data from a r and om sample of full-time nurses . Binary logistic regression models were used to examine the association between sleep variables , fatigue , and clinical -decision self-efficacy and regret . The discrimination of the models was compared with the C statistic , the area under the receiver operating characteristic curve . RESULTS A total of 605 nurses returned the question naires ( 17 % response rate ) . Among these , decision regret was reported by 157 of 546 ( 29 % ) . Nurses with decision regret reported more fatigue , more daytime sleepiness , less intershift recovery , and worse sleep quality than did nurses without decision regret . Being male , working a 12-hour shift , and clinical -decision satisfaction were significantly associated with decision regret ( C statistic , 0.719 ; SE , 0.024 ) . CONCLUSION Nurses who experience impairments due to fatigue , loss of sleep , and inability to recover between shifts are more likely than unimpaired nurses to report decision regret RATIONALE Little is known about the consequences of intensivists ’ work schedules , or intensivist continuity of care . OBJECTIVES To assess the impact of weekend respite for intensivists , with consequent reduction in continuity of care , on them and their patients . METHODS In five medical intensive care units ( ICUs ) in four academic hospitals we performed a prospect i ve , cluster-r and omized , alternating trial of two intensivist staffing schedules . Daily coverage by a single intensivist in half-month rotations ( continuous schedule ) was compared with weekday coverage by a single intensivist , with weekend cross-coverage by colleagues ( interrupted schedule ) . We studied consecutive patients admitted to study units , and the intensivists working in four of the participating units . MEASUREMENTS AND MAIN RESULTS The primary patient outcome was ICU length of stay (LOS);we also assessed hospital LOS and mortality rates . The primary intensivist outcome was physician burnout . Analysis was by multivariable regression . A total of 45 intensivists and 1,900 patients participated in the study . Continuity of care differed between schedules ( patients with multiple intensivists = 28 % under continuous schedule vs. 62 % under interrupted scheduling ; P < 0.0001 ) . LOS and mortality were nonsignificantly higher under continuous scheduling ( ΔICU LOS 0.36 d , P = 0.20 ; Δhospital LOS 0.34 d , P = 0.71 ; ICU mortality , odds ratio = 1.43 , P = 0.12 ; hospital mortality , odds ratio = 1.17,P = 0.41 ) . Intensivists experienced significantly higher burnout , work – home life imbalance , and job distress working under the continuous schedule . CONCLUSIONS Work schedules where intensivists received weekend breaks were better for the physicians and , despite lower continuity of intensivist care , did not worsen outcomes for medical ICU patients BACKGROUND The current status of needlestick or sharp injuries of hospital nurses and factors associated with the injuries have not been systematic ally examined with representative registered nurse sample s in South Korea . OBJECTIVE To examine the incidence to needlestick or sharp injuries and identify the factors associated with such injuries among hospital nurses in South Korea . DESIGN , SETTING S AND PARTICIPANTS A cross-sectional survey of hospital nurses in South Korea . Data were collected from 3079 registered nurses in 60 acute hospitals in South Korea by a stratified r and om sampling method based on the region and number of beds . METHODS The dependent variable was the occurrence of needlestick or sharp injuries in the last year , and the independent variables were protective equipment , nurse characteristics , and hospital characteristics . This study employed logistic regression analysis with generalized estimating equation clustering by hospital to identify the factors associated with needlestick or sharp injuries . RESULTS The majority ( 70.4 % ) of the hospital nurses had experienced needlestick or sharp injuries in the previous year . The non-use of safety containers for disposal of sharps and needles , less working experience as a registered nurse , poor work environments in regards to staffing and re source adequacy , and high emotional exhaustion significantly increased risk for needlestick or sharp injuries . Working in perioperative units also significantly increased the risk for such injuries but working in intensive care units , psychiatry , and obstetrics wards showed a significantly lower risk than medical-surgical wards . CONCLUSIONS The occurrence of needlestick or sharp injuries of registered nurses was associated with organizational characteristics as well as protective equipment and nurse characteristics . Hospitals can prevent or reduce such injuries by establishing better work environments in terms of staffing and re source adequacy , minimizing emotional exhaustion , and retaining more experienced nurses . All hospitals should make safety-engineered equipment available to registered nurses . Hospitals as well as specific units showing higher risk for needlestick and sharp injuries should implement organizational strategies to prevent such injuries . It is also necessary to establish a monitoring system of needlestick and sharp injuries at a hospital level and a reporting system at the national level in South Korea STUDY OBJECTIVES To examine the relationship between residents ' self-reported sleep hours , work hours , and other empirical correlates . DESIGN Using the American Medical Association 's Graduate Medical Education data base , a national , r and om sample of PGY ( postgraduate year ) 1 and PGY2 residents in the 1998 - 1999 training year was surveyed by mail . MEASUREMENTS AND RESULTS Residents completed a 5-page survey with 44 questions requiring 144 separate responses about their residency experience . Completed surveys were received from 3,604 of 5,616 residents contacted , a 64.2 % response rate . Although work hours and sleep hours were significantly correlated ( r = -.39 ) , this relationship was less robust than is generally assumed . Total average sleep hours varied across specialties but also within specialties . Just over 20 % of all residents reported sleeping an average of 5 hours or less per night , with 66 % averaging 6 hours or less per night . Residents averaging 5 or fewer hours of sleep per night were more likely to report serious accidents or injuries , conflict with other professional staff , use of alcohol , use of medications to stay awake , noticeable weight change , working in an " impaired condition , " and having made significant medical errors . CONCLUSIONS Reduced sleep hours were significantly related to a number of work-related , learning , and personal health variables . Capping residents ' work hours is unlikely to fully address the sleep deficits and result ing impairments reported by residents BACKGROUND Resident work hours may impact patient care . We hypothesized that " call-associated " acute sleep deprivation has no effect on technical dexterity as measured on a minimally invasive surgery trainer , virtual reality ( MIST VR ) surgical simulator . METHODS Thirty-five surgical residents were prospect ively evaluated pre-call ( rested ) , on-call ( rested ) , and post-call ( acutely sleep deprived ) . Participants completed question naires regarding sleep hours and level of fatigue . Technical skill was assessed using the MIST VR . Speed , errors , and economy of motion were automatically recorded by the MIST VR computer simulator . Data were analyzed by paired Student t test and analysis of variance . RESULTS Estimated hours of sleep and subjective indicators of fatigue were different between rested and sleep-deprived residents . The number of errors and time to complete all tasks increased at the post-call assessment . CONCLUSIONS Resident work schedules lead to sleep deprivation and fatigue . Call-associated sleep deprivation and fatigue are associated with increased technical errors in the performance of simulated laparoscopic surgical skills |
12,887 | 31,616,037 | Conclusion DNA methylation is significantly higher in CIN2 + and CIN3 + compared to ≤CIN1 .
As triage test , DNA methylation has higher specificity than cytology ASCUS+ and higher sensitivity than HPV16/18 genotyping | Background To conduct a meta- analysis of performance of DNA methylation in women with high- grade cervical intraepithelial neoplasia ( CIN2 + ) . | BACKGROUND Cytology is a widely used method of triaging women who test positive for human papillomavirus ( HPV ) . However , self- sample d specimens , which can substantially increase participation in screening programmes , are not suitable for accurate cytological assessment . We investigated whether direct DNA methylation-based molecular triage on self- sample d cervicovaginal specimens was non-inferior to cytology triage on additional physician-collected cervical sample s in the detection of cervical intraepithelial neoplasia grade 2 ( CIN2 ) or worse in women who did not attend cervical screening programmes . METHODS In this r and omised controlled non-inferiority trial , we invited women ( aged 33 - 63 years ) registered as non-attendees of cervical screening in the Netherl and s in 2007 to su bmi t a self-collected cervicovaginal sample for HPV testing . Using a computer-generated sequence , we r and omly allocated women who tested positive for high-risk hrHPV on a self- sample to either triage by cytology on an additional physician-taken smear or direct triage on the self- sample by methylation analysis of MAL and miR-124 - 2 genes ( 1:1 ; stratified by age and region , with block sizes by age group ) . Triage-positive women in either group were referred for colposcopy . The primary endpoint was detection of CIN2 or worse , analysed by intention to treat . The non-inferiority margin was 0·80 . This study is registered in the Primary Trial Register of the Netherl and s , number NTR6026 . FINDINGS We invited 46,001 women to participate , 12,819 of whom returned self- sample d material ; 1038 sample s tested positive for high-risk HPV . Between Nov 1 , 2010 , and Dec 31 , 2011 , after exclusion of women who were ineligible , we enrolled and r and omly allocated 515 women to methylation triage and 509 to cytology triage . The detection of CIN2 or worse with methylation triage was non-inferior to that with cytology triage ( 90 [ 17 % ] of 515 women vs 75 [ 15 % ] of 509 women ; relative risk 1·19 , 95 % CI 0·90 - 1·57 ) . Referral for colposcopy was more common in the molecular group ( 284 [ 55 % ] women ) than in the cytology group ( 149 [ 29 % ] women ; p<0·0001 ) . Mean time to CIN2 or worse diagnosis was shorter in the molecular triage group ( 96 days , range 44 - 101 ) than in the cytology triage group ( 158 days , 71 - 222 ; p=0·00084 ) . INTERPRETATION DNA methylation analysis of MAL and miR-124 - 2 genes on HPV-test-positive self- sample s is non-inferior to cytology triage in the detection of CIN2 or worse , opening the way to full molecular screening . FUNDING Midden-West and Oost Screening Organisations and Stichting Achmea Gezondheidszorg OBJECTIVE Our previous work revealed that host genes ZNF582 , PTPRR , PAX1 , and SOX1 are highly methylated in cervical intraepithelial neoplasias grade 3 or worse ( CIN3(+ ) ) . In this study , we used a st and ardized testing assay to evaluate the clinical efficacy of these biomarkers in the triage of cytological diagnoses of low- grade squamous intraepithelial lesions ( LSILs ) , and compared the performance with human papillomavirus ( HPV ) testing . METHODS This 2-year multicenter prospect i ve study examined a population of 230 women from 12 medical centers who were diagnosed with LSILs on cervical cytology . Cervical scrapings were obtained prior to a colposcopy-directed biopsy for quantitative methylation analysis of ZNF582 , PTPRR , PAX1 , and SOX1 , and HPV testing . Using logistic regression and receiver operating characteristic curve analyses , the abilities of methylated genes and HPV to predict CIN3(+ ) were assessed . RESULTS Fifteen ( 6.5 % ) of the 230 women with a cytological diagnosis of LSIL were confirmed to have CIN3(+ ) after a colposcopy-directed biopsy . Among the 4 methylated genes , ZNF582 was found to be the best biomarker for detecting CIN3(+ ) . The sensitivities for methylated ZNF582 and HPV testing were 73 % and 80 % , and the specificities were 71 % and 28 % , respectively . The odds ratio for predicting CIN3(+ ) using methylated ZNF582 was 6.8 ( 95 % confidence interval ( CI ) 2.1 - 22.1 ) , which was much better than HPV testing ( OR=1.6 , 95 % CI 0.4 - 5.8 ) . CONCLUSION This is the first study to show that ZNF582 methylation analysis of cervical swabs may be a promising choice in the positive triage of cytological diagnoses of LSILs An accurate biomarker for the follow-up of women positive for human papillomavirus type 16 ( HPV16 ) DNA may improve the efficiency of cervical cancer prevention . Previously , we analyzed all 113 HPV16 CpGs in cervical cytology sample s and discovered differential methylation at different stages of premalignancy . In the current study , we identified a methylation biomarker consisting of a panel of 12 HPV16 CpG sites in the E5 , L2 , and L1 open reading frames , and tested whether it fulfilled three necessary conditions of a prospect i ve biomarker . A total of 33 cytology sample s from North American and West African women with all grade s of cervical intraepithelial neoplasia ( CIN ) and invasive cervical cancer ( ICC ) were analyzed by using DNA bisulfite sequencing . The results showed ( i ) a highly significant trend for increasing HPV16 biomarker methylation with increasing histologic severity ( P < 0.0001 ) , ( ii ) 100 % sensitivity for ICC over a wide range of methylation cutoff scores ; 80 % detection of CIN3 at cutoff scores up to 39 % methylation , and ( iii ) substantially lower detection of CIN2 , from 0 % to 71 % , depending on the cutoff score . Our results support the prognostic potential of the HPV16 methylation biomarker for the triage to colposcopy of women with HPV16-positive screening tests and , eventually , for the management of women with HPV16-positive CIN2 . Cancer Prev Res ; 7(5 ) ; 526–33 . © 2014 AACR DNA methylation changes in human papillomavirus type 16 ( HPV16 ) DNA are common and might be important for identifying women at increased risk of cervical cancer . Using recently published data from Costa Rica we developed a classification score to differentiate women with cervical intraepithelial neoplasia grade 2 or 3 ( CIN2/3 ) from those with no evident high- grade lesions . Here , we aim to investigate the performance of the score using data from the UK . Exfoliated cervical cells at baseline and 6-months follow-up were analyzed in 84 women selected from a r and omized clinical trial of women undergoing surveillance for low- grade cytology . Selection of women for the methylation study was based on detectable HPV16 in the baseline sample . Purified DNA was bisulfite converted , amplified and pyrosequenced at selected CpG sites in the viral genome ( URR , E6 , L1 and L2 ) , with blinding of laboratory personnel to the clinical data . The primary measure was a predefined score combining the mean methylation in L1 and any methylation in L2 . At the second follow-up visit , 73/84 ( 87 % ) women were HPV16 positive and of these 25 had a histopathological diagnosis of CIN2/3 . The score was significantly associated with CIN2/3 ( area under curve = 0.74 , p = 0.002 ) . For a cutoff with 92 % sensitivity , colposcopy could have been avoided in 40 % ( 95 % CI 27–54 % ) of HPV16 positive women without CIN2/3 ; positive predictive value was 44 % ( 32–58 % ) and negative predictive value was 90 % ( 71–97 % ) . We conclude that quantitative DNA methylation assays could help to improve triage among HPV16 positive women Objective : Cervical cancer is the leading cause of cancer-related death in women in South Africa . This study evaluates DNA methylation levels in cervical (pre)cancer and aims to assess the value of high-risk human papillomavirus ( hrHPV ) testing and methylation analysis , alone or in combination , on physician-taken cervical scrapes to detect cervical cancer , and cervical intraepithelial neoplasia grade 3 ( CIN3 ) in an HIV-infected South African population . Design : Prospect i ve observational multicentre cohort study . Methods : Women from a cohort of women living with HIV ( n = 355 ) and a referral cohort ( n = 109 , 60 % HIV seropositive ) were included . Cervical scrapes were collected for hrHPV testing and methylation analysis of cell adhesion molecule 1 , T-lymphocyte maturation-associated protein , and microRNA124 - 2 genes . Histologic endpoints were available for all participants . Performance for detection of CIN3 or worse ( CIN3 + ) was determined in the cohort of women living with HIV and different testing strategies were compared . Results : HrHPV and methylation positivity rates increased with severity of cervical disease in the two study cohorts , each reaching 100 % in sample s of women with carcinoma . HrHPV testing showed a sensitivity for CIN3 + of 83.6 % , at a specificity of 67.7 % . Methylation analysis showed a comparable CIN3 + sensitivity of 85.2 % , but a significantly lower specificity of 49.6 % . HrHPV testing with reflex methylation analysis showed a CIN3 + sensitivity of 73.8 % , at a specificity of 81.5 % . Conclusion : In this HIV-infected South African population , stratifying hrHPV-positive women with reflex methylation analysis detects all cervical carcinomas and yields an acceptable sensitivity and specificity for CIN3 + Recently , DNA methylation analysis of FAM19A4 in cervical scrapes has been shown to adequately detect high- grade cervical intraepithelial neoplasia and cervical cancer ( ≥ CIN3 ) in high-risk HPV (hrHPV)-positive women . Here , we compared the clinical performance of FAM19A4 methylation analysis to cytology and HPV16/18 genotyping , separately and in combination , for ≥ CIN3 detection in hrHPV-positive women participating in a prospect i ve observational multi-center cohort study . The study population comprised hrHPV-positive women aged 18 - 66 years , visiting a gynecological outpatient clinic . From these women , cervical scrapes and colposcopy-directed biopsies ( for histological confirmation ) were obtained . Cervical scrapes were analyzed for FAM19A4 gene promoter methylation , cytology and HPV16/18 genotyping . Methylation analysis was performed by quantitative methylation-specific PCR ( qMSP ) . Sensitivities and specificities for ≥ CIN3 were compared between tests . Stratified analyses were performed for variables that potentially influence marker performance . Of all 508 hrHPV-positive women , the sensitivities for ≥ CIN3 of cytology , FAM19A4 methylation analysis , and cytology combined with HPV16/18 genotyping were 85.6 , 75.6 and 92.2 % , respectively , with corresponding specificities of 49.8 , 71.1 and 29.4 % , respectively . Both sensitivity and specificity of FAM19A4 methylation analysis were associated with age ( p ≤ 0.001 each ) . In women ≥ 30 years ( n = 287 ) , ≥ CIN3 sensitivity of FAM19A4 methylation analysis was 88.3 % ( 95%CI : 80.2 - 96.5 ) which was noninferior to that of cytology [ 85.5 % ( 95%CI : 76.0 - 94.0 ) ] , at a significantly higher specificity [ 62.1 % ( 95%CI : 55.8 - 68.4 ) compared to 47.6 % ( 95%CI : 41.1 - 54.1 ) ] . In conclusion , among hrHPV-positive women from an outpatient population aged ≥ 30 years , methylation analysis of FAM19A4 is an attractive marker for the identification of women with ≥ CIN3 OBJECTIVES Methylation marker analysis using bi-marker panel MAL/miR-124 - 2 is a promising triage test for identifying cervical (pre)cancer in high-risk human papillomavirus ( hrHPV ) positive women . Bi-marker panel MAL/miR-124 - 2 can be applied directly on self- sample d cervico-vaginal material and its sensitivity is non-inferior to that of cytology , yet at the cost of more colposcopy referrals . Our objective was to increase specificity of MAL/miR-124 - 2 methylation analysis by varying the assay thresholds and adding HPV16/18 genotyping . METHODS 1019 hrHPV-positive women were selected from a r and omized controlled self-sampling trial ( PROHTECT-3 ; 33 - 63 years , n=46,001 ) and nine triage strategies with methylation testing of MAL/miR-124 - 2 and HPV16/18 genotyping were evaluated . The methylation assay threshold was set at four different predefined levels which correspond with clinical specificities for end-point cervical intra-epithelial grade 3 or worse ( CIN3 + ) of 50 % , 60 % , 70 % , and 80 % . RESULTS The CIN3 + sensitivity of methylation analysis decreased ( 73.5 to 44.9 % ) while specificity increased ( 47.2 to 83.4 % ) when increasing the assay threshold . CIN3 + sensitivity and specificity of HPV16/18 genotyping were 68.0 % and 65.6 % , respectively . Combined methylation analysis at threshold-80 and HPV16/18 genotyping yielded similar CIN3 + sensitivity as that of methylation only at threshold-50 ( 77.6 % ) with an increased specificity ( 54.8 % ) . CONCLUSIONS Combined triage by MAL/miR-124 - 2 methylation analysis with threshold-80 and HPV16/18 genotyping reaches high CIN3 + sensitivity with increased specificity to identify women with cervical (pre)cancer among HPV self- sample positive women . The combined strategy is attractive as it is fully molecular and identifies women at the highest risk of cervical (pre)cancer because of strongly elevated methylation levels and /or HPV16/18 positivity The ongoing Triage and Risk Assessment of Cervical Precancer by Epigenetic Biomarker ( TRACE ) prospect i ve , multicenter study aim ed to provide a clinical evaluation of the CONFIDENCE ™ assay , which comprises a human papillomavirus ( HPV ) DNA and a human epigenetic biomarker test . Between 2013 and 2015 over 6,000 women aged 18 or older were recruited in Hungary . Liquid-based cytology ( LBC ) , high-risk HPV ( hrHPV ) DNA detection and single target host gene methylation test of the promoter sequence of the POU4F3 gene by quantitative methylation-specific polymerase chain reaction ( PCR ) were performed from the same liquid-based cytology sample . The current analysis is focused on the baseline cross-sectional clinical results of 5,384 LBC sample s collected from subjects aged 25 years or older . The performance of the CONFIDENCE HPV ™ test was found to be comparable to the cobas ® HPV test with good agreement . When applying the CONFIDENCE Marker ™ test alone in hrHPV positives , it showed significantly higher sensitivity with matching specificity compared to LBC-based triage . For CIN3 + histological endpoint in the age group of 25 - 65 and 30 - 65 , the methylation test of POU4F3 achieved relative sensitivities of 1.74 ( 95 % CI : 1.25 - 2.33 ) and 1.64 ( 95 % CI : 1.08 - 2.27 ) , respectively , after verification bias adjustment . On the basis of our findings , POU4F3 methylation as a triage test of hrHPV positives appears to be a noteworthy method . We can reasonably assume that its quantitative nature offers the potential for a more objective and discriminative risk assessment tool in the prevention and diagnostics of high- grade cervical intraepithelial neoplasia ( CIN ) lesions and cervical cancer We explored the association of human papillomavirus type 16 ( HPV16 ) DNA methylation with age , viral load , viral persistence and risk of incident and prevalent high grade CIN ( CIN2 + ) in serially collected specimens from the Guanacaste , Costa Rica cohort . 273 exfoliated cervical cell specimens ( diagnostic and pre‐diagnostic ) were selected : ( 1 ) 92 with HPV16 DNA clearance ( controls ) , ( 2 ) 72 with HPV16 DNA persistence ( without CIN2 + ) and ( 3 ) 109 with CIN2 + . DNA was extracted , bisulfite converted and methylation was quantified using pyrosequencing assays at 66 CpGs across the HPV genome . The Kruskal‐Wallis test was used to determine significant differences among groups , and receiver operating characteristic curve analyses were used to evaluate how well methylation identified women with CIN2 + . In diagnostic specimens , 88 % of CpG sites had significantly higher methylation levels in CIN2 + after correction for multiple tests compared with controls . The highest area under the ROC curve ( AUC ) was 0.82 for CpG site 6457 in L1 , and a diagnostic sensitivity of 91 % corresponded to a specificity of 60 % for CIN2 + . Prospect ively , 17 % of CpG sites had significantly higher methylation in pre‐diagnostic CIN2 + specimens ( median time of 3 years before diagnosis ) versus controls . The strongest pre‐diagnostic CpG site was 6367 in L1 with an AUC of 0.76 . Age‐stratified analyses suggested that women older than the median age of 28 years have an increased risk of precancer associated with high methylation . Higher methylation in CIN2 + cases was not explained by higher viral load . We conclude that elevated levels of HPV16 DNA methylation may be useful to predict concurrently diagnosed as well as future CIN2 + OBJECTIVES Triage of HPV screen-positive women is needed to identify those with underlying cervical intraepithelial neoplasia grade 2/3 or worse ( CIN2/3 + ) . Presently , cytology on a physician-taken cervical scrape is mostly accepted as triage test , but needs follow-up testing in order not to miss severe disease . Here , we evaluated the performance of combined cytology and bi-marker CADM1/MAL-methylation analysis as triage test on physician-taken cervical scrapes of HPV positive women . METHODS In this post-hoc analysis , we used 364 left-over HPV positive cytology triage sample s of participants of a r and omized controlled trial ( PROHTECT-3 : n=46,001 ) performed in population -based cervical screening . Study endpoints were CIN2 + and CIN3 + detection . Cytology testing with and without methylation marker analysis was evaluated with regard to sensitivity , specificity , positive and negative predictive value , and referral rate . RESULTS Bi-marker CADM1/MAL-methylation positivity increased proportionally with severity of underlying lesions . Overall , cytology and bi-marker CADM1/MAL-methylation analysis yielded similar performances with regard to CIN3 + detection , yet in combination a significantly higher sensitivity for CIN3 + ( 88.7 % ) was obtained at a specificity of 53.6 % and a colposcopy referral rate of 53.6 % . The combined strategy detected all six cervical cancers , whereas triage by cytology alone failed to detect two of them . CONCLUSIONS Cytology and bi-marker CADM1/MAL-methylation analysis perform complementary for CIN2+/CIN3 + detection when used as triage tool on cervical scrapes of HPV positive women . This approach not only results in a higher CIN3 + sensitivity than cytology triage with an acceptable referral rate , but also seems to reduce the risk of missing cervical cancers and advanced high- grade lesions Objectives : To evaluate the value of cervical cell methylation markers in screening HIV-infected women also positive for high-risk human papillomavirus ( hrHPV ) . Design : Cross-sectional and prospect i ve . Methods : Two hundred forty-eight HIV-infected hrHPV-positive women enrolled in a cervical cancer screening study in Nairobi , Kenya , had colposcopy-directed biopsy and histological diagnoses . Exfoliated cervical cells were used to measure methylation levels of the CADM1 , MAL , and MIR124 - 2 genes using quantitative methylation-specific polymerase chain reaction . Methylation levels were summarized as cycle threshold ( Ct ) ratios compared with the & bgr;-actin gene . Median Ct ratios were compared across histological diagnoses , with 95 % confidence intervals calculated by bootstrapping . Methylation levels at 6 months were assessed in 128 women who remained hrHPV positive . Results : All 3 methylation markers showed significantly ( P < 0.001 ) raised median Ct ratios in women with cervical intraepithelial neoplasia ( CIN ) grade 3 compared with women with a normal cervix . When markers were combined into a single test , the area under the receiver operating characteristic curve for prediction of CIN2 or worse ( CIN2 + ) was 0.80 . When the test was calibrated to have similar specificity , sensitivity of the combined tri-marker test for CIN2 + was comparable with cytology [ atypical squamous cells of undetermined significance or worse ] ( 89 % and 95 % , respectively ) and superior to visual inspection with acetic acid ( 85 % vs 70 % ) and HPV16/18 genotyping ( 65 % vs 40 % ) . Among women with no CIN2 + at baseline and persistent hrHPV at 6-month follow-up , MAL-m1 and MIR124 - 2 Ct ratios increased significantly . Conclusions : Methylation markers in combination with HPV testing may offer a full molecular screening strategy to the many HIV-infected women who are also hrHPV positive Objective DNA methylation has been shown to be a potential biomarker for early cancer detection . The aim of this study was to evaluate DNA methylation profiles according to liquid-based Pap ( LBP ) test results and to assess their diagnostic value in a Korean population . Methods A total of 205 patients with various Papanicolaou test results were enrolled to this study ( negative , 26 ; atypical squamous cells of undetermined significance , 39 ; low grade squamous intraepithelial lesion , 44 ; high grade squamous intraepithelial lesion ( HSIL ) , 48 ; and cancer , 48 ) . DNA methylation analysis of four genes , ADCYAP1 , PAX1 , MAL , and CADM1 , was performed on residual cervical cells from LBP sample s using a quantitative bisulfite pyrosequencing method . To evaluate the diagnostic performance of the four methylated genes for cancer detection , receiver operating characteristic ( ROC ) curves were drawn . Sensitivities and specificities were also tested at cutoffs determined from the ROC curves . Results Cervical cancer cells showed dramatically increased methylation levels for the four genes analyzed . ADCYAP1 and PAX1 also trended toward elevated methylation levels in HSIL sample s , although the levels were much lower than those in cancer cells . The sensitivities of methylated ADCYAP1 , PAX1 , MAL , and CADM1 for the detection of cancer were 79.2 % , 75.0 % , 70.8 % , and 52.1 % , and the specificities were 92.0 % , 94.0 % , 94.7 % , and 94.0 % , respectively . Methylated ADCYAP1 and PAX1 demonstrated relatively better discriminatory ability than did methylated MAL and CADM1 ( area under the curves 0.911 and 0.916 vs. 0.854 and 0.756 , respectively ) . Conclusion DNA methylation status , especially in the ADCYAP1 and PAX1 genes , showed relatively good specificity , ranging from 90 % to 94 % . The possible additive and complementary roles of DNA methylation testing with respect to conventional cervical cancer screening programs will need to be vali date d in prospect i ve population -based studies Wound contact layer ( WCL ) dressings are intended to protect tissue during the healing process . A r and omised controlled trial was undertaken to compare 2 such dressings . Out patients with acute wounds were r and omly allocated to treatment with either a soft silicone-coated WCL ( intervention group , n = 59 ) or a lipidocolloid-impregnated WCL ( control group , n = 62 ) . At the first dressing removal ( day 3 ) , 89.8 % of patients in the intervention group experienced non-painful dressing removal ( defined as a pain rating < 30 mm on a 100 mm visual analogue scale ) , compared with 73.6 % of patients in the control group ( P = .017 ) ( per protocol population ) . At day 21 , wounds were considered as healed in 66.1 % of patients in the intervention group compared with 43.5 % in the control group ( P = .012 ) ( intention-to-treat population ) . Both dressings were well tolerated and rated highly in terms of in-use characteristics , although the soft silicone-coated WCL was rated significantly higher than the lipidocolloid-impregnated WCL in terms of its ability to remain in place ( P= .016 ) . The results indicate that the soft silicone-coated WCL is suitable for the management of acute wounds as it can minimise dressing-associated pain and support healing Objectives DNA methylation is a potential biomarker for early cancer detection . Previous studies suggested that the methylations of several genes are promising markers for the detection of cervical intraepithelial neoplasia at grade III or worse ( CIN3 + ) . The purpose of the present study was to explore the feasibility of these DNA methylation testing in cervical cancer screening . Methods A total of 443 women were recruited from the Yuan ’s General Hospital . Cervical scrapings were collected for Papanicolaou ( Pap ) test by using cervical brushes , and the cytological data were used for analysis . The residual cells on the brush were preserved in phosphate-buffered saline solution at 4 ° C until DNA extraction . Then , the extracted DNA were used for molecular tests , which included human papillomavirus typing and quantification of the methylation levels for PAX1 , SOX1 , and NKX6 - 1 genes . Subjects who had abnormal Pap test results underwent colposcopy or biopsy with subsequent conization or major surgery when biopsy results revealed CIN2 + . The final diagnosis for this group was confirmed by colposcopy or pathological examination . The study was approved by the institutional review board of Yuan ’s General Hospital , and all the molecular tests were performed by ISO17025 certified laboratories . Results The sensitivity of PAX1 m and SOX1 m was greater than 80 % , and the specificity of PAX1 m and NXK6 - 1 m was greater than 80 % for the detection of CIN3 + lesions . PAX1 m detection alone had a sensitivity and specificity of 86 % and 85 % , respectively , whereas when used as a cotest with the Pap test , the sensitivity and specificity were 89 % and 83 % , respectively . Conclusions PAX1 m showed great potential as a biomarker for cervical cancer screening . When incorporating PAX1 m detection into current screening protocol , the efficacy of screening could be greatly improved . Moreover , unnecessary referral for colposcopy and biopsy could be reduced up to 60 % . However , prospect i ve population -based studies are necessary for further implementation of this screening program Human papillomavirus (HPV)‐based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 ( CIN2 ) or worse . We conducted a blinded case – control study within the HPV FOCAL r and omized cervical cancer screening trial of women aged 25–65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping . Groups were r and omly selected from women with known HPV/cytology results and pathology outcomes . Group 1 : 104 HPV positive ( HPV+ ) , abnormal cytology ( 54 CIN2/3 ; Background To explore the diagnostic value of FAM19A4 methylation in high-risk human papilloma virus (hrHPV)-positive cervical sample s from Chinese women for estimating cervical cancer or its precancerous lesions . Methods Cervical sample s from 215 women infected with high-risk HPV were collected by smear testing . We purpose ly chose 61 patients with cervical cancer , 57 with high- grade squamous intraepithelial lesions ( HSIL ) , 31 with low- grade squamous intraepithelial lesions ( LSIL ) , and 66 without cervical intraepithelial neoplasia ( CIN ) after histological confirmation . Taqman probe-based quantitative PCR ( qPCR ) was utilized to detect the methylation status of FAM19A4 in the cervical sample s and further evaluate the use of this gene in the diagnosis of cervical cancer . Results ( 1 ) An increasing level of FAM19A4 methylation was detected with increasing progression of cervical lesions , with methylation rates of 10.61%(7/66 ) , 35.48%(11/31 ) , 56.14%(32/57 ) and 93.44%(57/61 ) in no CIN , LSIL , HSIL and cervical carcinoma sample s respectively . ( 2 ) In all hrHPV-positive sample s , the levels of FAM19A4 methylation in HPV16/18 groups were higher than that in 12 other hrHPV groups ( P < 0.05 ) , but there was no significant difference between two groups after grouping cervical lesions into cervical cancer , HSIL , LSIL and no CIN groups ( P>0.05 ) . (3)There were no significant differences of FAM19A4 methylation in different clinicopathological parameters of cervical cancer . ( 4 ) Though the sensitivity of FAM19A4 methylation test was inferior to that of cytology and FAM19A4 combining with HPV16/18 genotyping , but showed the best specificity with 81.44 % both for detection HSIL alone and ≥ HSIL , with favorable youden index ( YI ) and area under curve ( AUC ) . Conclusion FAM19A4 is a specific biomarker of cancerous lesions of the cervix . FAM19A4 methylation analysis may serve as an auxiliary screening method for diagnosis of cervical (pre)cancer . However , in consideration of the limitations of this retrospective study , prospect i ve population -based studies are necessary for further confirmation of the diagnostic value of FAM19A4 methylation for detection of cervical (pre)cancer in Chinese women BACKGROUND Previous studies have suggested an association between human papillomavirus type 16 ( HPV16 ) genome methylation and cervical intraepithelial neoplasia grade 3 ( CIN3 ) ( ie , cervical precancer ) and cancer , but the results have been inconsistent . METHODS We design ed a case-control study within a large prospect i ve cohort of women who underwent multiple screenings for cervical cancer in Guanacaste , Costa Rica . Diagnostic specimens were collected at the time of CIN3 diagnosis ( n = 30 case subjects ) and persistent HPV16 infection ( persistence ; n = 35 case subjects ) , prediagnostic specimens at the first HPV16-positive screening visit ( n = 20 CIN3 case subjects ; n = 35 persistence case subjects ) , and control specimens from women with infection clearance within 2 years ( n = 34 control subjects ) . DNA extracted from specimens ( cervical cells ) was analyzed for methylation levels at 67 CpG sites throughout the HPV16 genome using pyrosequencing . Benjamini-Hochberg method was used to account for multiple testing . Associations between methylation levels and risk of CIN3 or persistence were assessed using logistic regression models to estimate odds ratios ( ORs ) and 95 % confidence intervals ( CIs ) . RESULTS Increased methylation in diagnostic vs control specimens at nine CpG sites , three in each L1 , L2 , and E2/E4 genomic regions , was associated with an increased risk of CIN3 ( third tertile [ high ] vs first and second tertiles combined [ low ] , OR = 3.29 [ 95 % CI = 1.16 to 9.34 ] to 11.12 [ 95 % CI = 2.29 to 76.80 ] ) and persistence . High methylation at three of these CpG sites was associated with a much higher risk when combined compared with low methylation at these sites ( OR = 52 , 95 % CI = 4.0 to 670 ) . In prediagnostic vs control specimens , increased methylation at a CpG site ( nucleotide position 4261 ) in L2 was associated with an increased risk of CIN3 . CONCLUSION In this HPV16-infected cohort , increased methylation of CpG sites within the HPV16 genome before diagnosis and at the time of diagnosis was associated with cervical precancer |
12,888 | 28,111,172 | Age , sex , and educational and income levels were the main determinants of SMA .
Socio-cultural , economic , and regulatory factors were the most commonly cited reasons for SMA .
Penicillins were the antibiotics most commonly used ; the antibiotics were obtained mainly via stored leftover drugs , pharmacies without prescriptions , and friends/relatives .
SMA was mainly for upper respiratory tract problems . | OBJECTIVES There has been no review on the prevalence , possible causes , and clinical outcomes of self-medication with antibiotics ( SMA ) in the Middle East . | Background The emergence and spread of bacterial resistance to antibiotics is a growing problem worldwide , which presents a significant threat to public health globally in the 21st century . A substantial evidence has shown that the general community plays a role in the increase and spread of antibiotic resistance . The present study was design ed to determine knowledge , attitude and practice towards antibiotic use . Methods A cross-sectional survey was performed using a pretested self-administered question naire on a sample of 770 r and omly selected Kuwaiti individuals . Descriptive and multivariate logistic regression analysis were used in data analysis . Results The response rate was 88.3 % . Nearly three-quarters ( 72.8 % ) of respondents had been prescribed antibiotics within 12 months prior to the study period , and 36 % of them had not finished the course of treatment . Over one-quarter ( 27.5 % ) were self-medicated with antibiotics to treat mainly common cold , sore throat and cough . Self-medication was more prevalent among those who were prescribed antibiotics and those who had attitudes towards using and accessing antibiotic inappropriately . Almost 47 % of participants had low knowledge regarding action , use , safety and resistance of antibiotics . Forty one percent of respondents had attitudes towards using and accessing antibiotic inappropriately . Better knowledge was found to be a predictor for positive attitude . Respondents level of agreement that doctors often prescribe antibiotics to meet the patient ’s expectation , and that doctors often take time to consider carefully the need for an antibiotic were 52.7 % and 35.3 % , respectively . Conclusions These findings will aid in the assessment of the adequacy of present public educational campaigns . Also , it will provide further insight in design ing future multifaceted interventions to promote specific messages to rationalize antibiotic use , and compensate for knowledge and attitude gaps as an effort towards preventing development of antibiotic resistance Background . Antibiotics are responsible for most dramatic improvement in medical therapy in history . These medications contributed significantly to the decreasing mortality and morbidity when prescribed based on evidence of microbial infection . Objective . The aim of this study was to determine the prevalence and predictors of self-prescription with antibiotics in Al Wazarat Health Center , Riyadh City , Kingdom of Saudi Arabia . Material and Methods . Cross-sectional study was conducted in Al Wazarat Health Center between February 2014 and November 2014 . Respondents were r and omly selected using a multistage clustered r and om sampling technique . Data was entered into SPSS version 21 and analyzed . Descriptive statistics and multiple logistic regression models were applied . Results . A total of 681 patients have participated in this study with a response rate of 92 % . The prevalence of self-prescription with antibiotics in Al Wazarat Health Center was 78.7 % . Amoxicillin was the most used self-prescribed antibiotic with prevalence of ( 22.3 % ) . Friend advice on self-prescription of antibiotics use ( p = 0.000 ) and pharmacy near to the participants ( p = 0.002 ) were the most common predictors for self-prescription with antibiotics . Conclusion . The level of self-prescribing antibiotics is relatively high among participants . Health education on the appropriate use of antibiotics is highly recommended . The proper use of treatment guidelines for antibiotic therapy will significantly reduce self-prescription with antibiotics Since the dawn of therapeutics , the prescribing of medications and their use by patients has been marked by substantial variability in both rationality and effectiveness . Drug use historically has reflected the highest principles of science as well as strikingly irrational behavior . This heterogeneity has been particularly vivid in the case of antibiotics . Antibiotics are among the most commonly used therapeutic agents , accounting for 12 % of ambulatory care prescriptions ( 1 ) . Their use ranges from treatment of minor self-limited outpatient symptoms to potentially fatal conditions in critically ill patients . Antibiotics loom large economically as well , accounting for approximately 15 % of the nearly $ 100 billion in annual medication expenditures in the United States ( 2 ) . Because of their role in treating infections , antibiotics tap into some of our most deeply held beliefs about bodily integrity and invasion . Furthermore , other than certain vaccines , antibiotics are the only drug class whose use influences not just the patient being treated but the entire ecosystem in which he or she lives , with potentially profound consequences . The determinants of antibiotic use and misuse are thus of particular importance . They include factors as diverse as the physicianpatient relationship , clinical microbiology , health economics , and the most basic definitions of illness and therapy ( 3 ) . Factors Leading to Antibiotic Misuse In their psychosocial dimension , medications can have properties that transcend pharmacology and may take center stage in some clinical situations . Social scientists and wise clinicians have long been aware that providing a patient with a drug is an interpersonal as well as a biochemical intervention ( 4 ) ; this is particularly true of antibiotics . The writing of a prescription signifies that the physician has made a diagnosis and that treatment is possible . A prescription officially ( and tangibly ) assigns the patient to the sick role , with all of its benefits and responsibilities ( 5 ) . It can also act as a termination strategy for an office visit , a sign that the visit has been consummated , the encounter is complete , and it is time for the patient to move on . This strategy creates a paradoxical outcome in the current environment , which is so preoccupied with throughput . A prescription for an antibiotic is often seen as the quickest way to end the visit of a patient with possible infectious symptoms . The number of patients seen per hour is increasing , and such increased productivity is frequently commended in the same management memor and um that criticizes out-of-control drug expenditures . Ironically , managers ' desire to reduce the use of diagnostic tests ( cultures ) and prevent return visits also creates pressures that favor heavy antibiotic use . Through the alchemy of the pharmacy , the paper prescription and its inscrutable ritualistic writings are transformed into a container of tablets or capsules . In a real sense , the drug prescription prolongs the physicianpatient encounter by enabling the patient to ingest a dose of the doctor several times a day . As Sir William Osler noted , The desire to ingest medicines is one of the principal features which distinguish man from the animals ( 6 ) . This perspective helps to explain the drug hunger that many symptomatic patients bring to the physician visit , in which they feel satisfied only by receiving a prescription ( 7 ) . Such dem and s are not based on clinical data as we know it ( 8 - 10 ) . Patient expectations have been further intensified by the advent of direct-to-consumer advertising of antibiotics by pharmaceutical manufacturers . Unlike the situation of depression , incontinence , or impotence , for which undertreatment is common , no logic exists for increasing the public 's dem and for antibiotics . These advertisements serve primarily to persuade patients to dem and newer , more costly antibiotics in clinical situations in which older , generic products , or no drug at all , would often work just as well . They are skillfully constructed to promote the ease or effectiveness of the target product and , of course , do not mention cost or note the similar effects of older therapies ( 11 ) . Two trends have intensified the effect of direct-to-consumer promotion of antibiotics . First , the credibility of many once-respected sources of authority is waning , taking a toll on physicians ' professional sovereignty ( 12 , 13 ) . Related to this trend is the parallel rise of consumer activism ; worried that their health maintenance organization will deny them needed therapy to reduce expenditures , patients dem and treatments that they fear might otherwise be withheld . Taken together , these trends turn therapeutic decision making into more of a dialogue ( at best ) or a tug-of-war ( at worst ) between patient and physician , a phenomenon that would have been unthinkable a generation ago . Add to this a growing if belated concern over patient satisfaction , the drive to shorten outpatient encounters as much as possible , and aggressive marketing directed at physicians , and the stage is set for the dem and and receipt of astoundingly large quantities of unnecessary antibiotics . Viewed in this context , it is not surprising that the small voice of therapeutic restraint and concern about microbial resistance is so difficult to hear above the din . The movement favoring adoption of clinical guidelines for rational antibiotic use often runs headlong into the pressures on the primary care physician as the proprietor of a small business , just trying to get through the day and satisfy his or her customers . For example , in focus groups design ed to reveal physicians ' knowledge about , attitudes toward , and motivations for prescribing , some clinicians presented with clinical vignettes that were constructed to sound compellingly viral in cause still favored use of antibiotics to improve symptoms and reduce the likelihood of superinfection ( 14 ) . However , a larger group argued that even if antibiotics were not indicated , they often felt obliged to prescribe them because of patient dem and . This problem is still more acute in the developing world , although a full discussion is beyond the scope of this paper . In the inpatient setting , a different set of forces conspires to encourage excessive antibiotic use . In teaching hospitals , prescribing decisions frequently are made by those with the least clinical experience ( interns and residents ) ; at the same time , each year hospitalized patients become more acutely ill and their cases increasingly complex . These factors , combined with the ubiquitous pressure to keep length of stays short ( the inpatient equivalent of the shrinking office visit ) , make it difficult to pursue a course of watchful waiting in managing a fever of unknown origin . Such temperance is particularly difficult if the prescribing physician has been in practice for only a few months . The first priority becomes the prevention of disaster within the next 24 hours , a goal often thought to be met best by broad-spectrum antibiotics or a cacophony of narrower-spectrum agents used in combination . Evidence for Antibiotic Misuse The perspective outlined above helps explain why analyses of antibiotic use patterns have consistently documented that prescribing is suboptimal ( 15 ) . Many r and omized , placebo-controlled trials of acute bronchitis , cough , and upper respiratory illnesses have found that outcomes are no better in typical patients taking antibiotics than in those given placebo ( 8 - 10 ) . However , of the 51 million visits for colds , upper respiratory tract infections , and bronchitis in the United States in one recent year , 50 % to 66 % culminated in an antibiotic prescription ( 16 , 17 ) . Clinical factors often seem to play a minor role in antibiotic decision making in these illnesses . Diagnostic uncertainty also plays a role ; a recent study of patients with sore throats found that two thirds of antibiotic prescriptions were written for patients whose cultures came back negative ( 18 ) . A large current survey of antibiotic use in treating infectious symptoms in children revealed widespread disregard of commonly recommended diagnostic strategies and therapeutic guidelines and frequent overuse of antibiotics in upper respiratory tract infections ( 65 % ) ( 19 ) . Several patient demographic factors have been found to increase the likelihood that antibiotics will be prescribed . These include being female , young , and white and living in a rural area ( 15 ) . In the developing world , social and economic factors as well as suboptimal drug use have driven the emergence and spread of multidrug-resistant tuberculosis ( 20 ) . In hospitalized patients , incorrect dosing or poor choice of drug occurs often . In a study performed at one teaching hospital ( 21 ) , we found that physicians usually ordered inappropriate doses or intervals for clindamycin , metronidazole , and cefazolin . At another large hospital , antibiotic prophylaxis before surgery was found to be correctly timed in only 40 % of cases ( 22 ) . At the same institution , physicians did not respond correctly to 25 % of instances in which culture and sensitivity data were available ( 23 ) . Overuse of such antibiotics as vancomycin raises concern about the emergence of resistant organisms as well as cost . One recent study found that only 40 % of orders at several hospitals were compatible with Centers for Disease Control and Prevention ( CDC ) guidelines ( 24 ) . Overuse of vancomycin is probably an important factor in the spread of resistance ( 25 ) ; during a period when vancomycin use was rapidly increasing , resistance rates increased from 0.8 % to 4.0 % ( 26 ) . Antibiotic Resistance and Costs The total costs associated with antibiotics come from multiple sources : medication , adverse events , and the often hidden cost of antimicrobial resistance ( 2 ) . Adverse events occur in a small proportion of antibiotic courses , but because of the frequency of antibiotic use , they accounted for 23 % of all adverse events recorded at one INTRODUCTION Antimicrobial resistance is a serious global health concern . It has considerable implication s on societies ' health and re sources . In Jordan , there is a large Iraqi community due to the ongoing turmoil in Iraq . Unfortunately , health awareness and practice s of this community are under-investigated due to scarcity of research . This paper assesses the awareness of antibiotic use and antimicrobial resistance in the Iraqi community residing in Amman , Jordan . Their level of interaction with health care professionals regarding antibiotics and differences in their antibiotic use between Iraq and Jordan are also discussed . METHODOLOGY A cross-sectional question naire-based survey involving r and omly selected Iraqis residing in Amman , Jordan was conducted . RESULTS The study involved 508 participants . Sixty-two percent of participants agreed with buying antibiotics without a prescription , 29 % agreed with obtaining antibiotics from friends or relatives , and 46 % agreed with keeping leftover antibiotics for future use . Furthermore , 60 % disagreed with not completing an antibiotic course and almost 90 % of the sample listed viral diseases as an indication for antibiotics . Forty-four percent of participants abided by physicians ' instructions on antibiotic use . Half of the participants believed that pharmacists provided instructions on antibiotics all the time , whereas physicians were perceived to do so by 29 % of participants . CONCLUSIONS Gaps exist in knowledge of antibiotic use and reasons for antimicrobial resistance among Iraqis residing in Jordan . These gaps should serve in planning educational campaigns to raise the community 's awareness of responsible antibiotic use . Law enforcement to restrict access to antibiotics is also pivotal to tackle their misuse INTRODUCTION Inappropriate use of antibiotics has result ed in a dramatic increase of antimicrobial resistance in developing countries . We examined knowledge , attitudes , and practice s of antibiotic use in three Asian countries . METHODOLOGY A nationwide cross-sectional study of teachers in large cities of Yemen , Saudi Arabia , and Uzbekistan was conducted . A r and om sample of 1,200 teachers was selected in each country . Data were collected through a question naire-based survey and then analyzed using descriptive and multivariate statistical methods . RESULTS The prevalence of non-prescription antibiotic use ranged from 48 % in Saudi Arabia to 78 % in Yemen and Uzbekistan . Pharmacies were the main source of non-prescribed antibiotics . The most common reasons for antibiotic use were cough ( 40 % ) and influenza ( 34 % ) . Forty-nine percent of respondents discontinued antibiotics when they felt better . Although awareness of the dangers of antibiotic use correlated inversely with self-medication , underst and ing of the appropriate use of antibiotics was limited . CONCLUSIONS The prevalence of antibiotic self-medication in the educated adult population in the studied countries was found to be alarmingly high . Effective strategies involving regulatory enforcement prohibiting sales of antibiotics without prescription should be implemented along with educational interventions for health professionals and the public Introduction This survey evaluates knowledge , attitudes and practice s of medical students towards use of antibiotics for upper respiratory infections ( URTIs ) . Methodology Cross-sectional question naire study among 1042 r and omly selected medical students in Saudi Arabia . Results Respondents were mostly Saudis ( 97.5 % ) , had previous knowledge of antibiotics ( 99.7 % ) and their usage ( 98.3 % ) against bacterial infections ( 93.7 % ) . 18.1 % thought that they could be used for viral infections . Nearly all students ( 97.2 % ) used antibiotics themselves during the previous year and self-medication without a prescription was high at 49 % of cases . Most antibiotics were taken for URTI symptoms ( 61.8 % ) . Female medical students had better knowledge on antibiotic effectiveness against bacteria and viruses , and overall knowledge increased with study year . Health seeking behaviour rates for symptoms of RTI and associated estimated necessity for antibiotics varied but were highest for cough with yellow/green phlegm . Conclusions The depth of knowledge that healthcare professionals have in relation to the proper use of antibiotics is essential in spreading the right message within communities . This is the first large study among medical students in Saudi Arabia , shedding important light on areas for improvement in the medical curriculum as well as antibiotic practice s of medical students themselves OBJECTIVE This study was aim ed to assess public knowledge , belief and behavior towards antibiotics use in a general population in the Sultanate of Oman . METHODS A 12-item self-administered question naire was distributed to 850 prospect i ve participants by research ers using quota sampling in two governorates of Oman . The data obtained were evaluated to assess the responses to individual questions related to knowledge , belief and behavior of antibiotic use . Median score of the respondents was correlated with participant demographics and status on use of antibiotics . RESULTS A total of 718 completed question naires were obtained giving a response rate of 85 % . The median total score of the participants was 16 ( Interquartile range : 6 ) out of a possible maximum score of 24 . A moderate knowledge and behavior score was observed , while the belief score of the participants was low . A significant difference was observed in the median total score based on age group , educational qualification and employment status . CONCLUSION Antibiotics are frequently used by the public . An inappropriate belief on antibiotic related aspects was observed and inappropriate behavior was noticed , which are reflections of insufficient knowledge and wrong beliefs . Interventions must be put in place to educate the public on appropriate antibiotic use BACKGROUND Parent education is an integral component to promoting judicious antibiotic use . Opportunities to educate parents directly are limited . Child care providers are in a position to relay information to parents . METHODS A group-r and omized trial assessed the impact of a child care center staff intervention on parental knowledge and attitudes regarding appropriate antibiotic use . A 9-point knowledge score and 3 attitude items were measured . RESULTS Surveys were returned by 151 ( 51 % ) of 298 intervention center parents and 150 ( 42 % ) of 361 control center parents . Intervention center respondents were significantly more likely than control center respondents to be college graduates , non-Hispanic white , and insured . Among college graduates , the median knowledge score was 7.0 at intervention centers and 6.5 at control centers ( P<0.01 ) . No significant differences were found in knowledge scores among noncollege educated parents ( P=0.11 ) . After adjusting for clustering within child care centers , multivariate analysis demonstrated high knowledge score was associated with white race ( P=0.02 ) , being a college graduate ( P=0.02 ) , and being in the intervention group ( P=0.06 ) . CONCLUSION An appropriate antibiotic use program for child care providers promotes better knowledge among parents of children aged < 5 years , particularly among highly educated parents Antibiotic misuse contributes to the growing problem of microbial resistance . To underst and the current knowledge and practice s regarding antibiotic use among Syrians , we conducted a cross-sectional study of 430 r and omly selected adult residents of Kalamoon in the Syrian Arab Republic using a question naire . A high proportion ( 85 % ) had taken antibiotics in the past 4 weeks and 34 % were not aware of the dangers of antibiotics . Of 365 participants , only 43 % were prescribed the antibiotic by a physician to treat the condition , while 57 % used an old prescription or took someone else 's advice . Males , younger individuals , and those with low and medium income and lower educational status showed poorer practice and lower knowledge towards antibiotics . Educational efforts are needed to reduce patient dem and for antibiotics This study is the first of its type to evaluate sources , patterns and appropriateness of antibacterial drug consumption within the Jordanian population . It uses a structured r and om interview to customers arriving at community pharmacy stores seeking antibacterial medication for systemic infections . Dispensed antibacterial drugs belonged to eight different main classes of systemically used antibacterial drugs in accordance with the Anatomical Therapeutic Chemical ( ATC ) classification system . Just less than one-half of all dispensed antibacterial drugs were without a prescription ( 46 % ) , either via self-medication ( 23.2 % ) or pharmacist recommendation ( 23.1 % ) . Inappropriateness in use was seen in 29.9 % and 34 % of the prescribed and non-prescribed ( over-the-counter ) antibacterial drugs , respectively . No uniformity in the treatment profile of the different treated complaints was seen . Our study shows great misuse and abuse of antibacterial drugs and hence there is a need to force regulations to control community use of antibacterial drugs and to increase awareness of the consequences of their inappropriate and uncontrolled use OBJECTIVE . The goal was to determine the impact of a community-wide educational intervention on parental misconceptions likely contributing to pediatric antibiotic overprescribing . METHODS . We conducted a cluster-r and omized trial of a 3-year , community-wide , educational intervention directed at parents of children < 6 years of age in 16 Massachusetts communities to improve parental antibiotic knowledge and attitudes and to decrease unnecessary prescribing . Parents in 8 intervention communities were mailed educational newsletters and exposed to educational material s during visits to local pediatric providers , pharmacies , and child care centers . We compared responses from mailed surveys in 2000 ( before the intervention ) and 2003 ( after the intervention ) for parents in intervention and control communities . Analyses were performed on the individual level , clustered according to community . RESULTS . There were 1106 ( 46 % ) and 2071 ( 40 % ) respondents to the 2000 and 2003 surveys , respectively . Between 2000 and 2003 , the proportion of parents who answered ≥7 of 10 knowledge questions correctly increased significantly in both intervention ( from 52 % to 64 % ) and control ( from 54 % to 61 % ) communities . We did not detect a significant intervention impact on knowledge regarding appropriate antibiotic use in the population overall . In a sub analysis , we did observe a significant intervention effect among parents of Medicaid-insured children , who began with lower baseline knowledge scores . CONCLUSIONS . Although knowledge regarding appropriate use of antibiotics is improving without additional targeted intervention among more socially advantaged population s , parents of Medicaid-insured children may benefit from educational interventions to promote judicious antibiotic use . These findings may have implication s for other health education campaigns Factors associated with antibiotic use , resistance and safety have been well recognized worldwide in the literature . Nevertheless , only few studies have been conducted in Jordan in this area . The aim of this study was to assess knowledge , behavior and attitude toward antibiotics use among adult Jordanians . The study represents a cross sectional survey using an interviewer administered question naire . Data collected from a r and om sample of 1141 adult Jordanians , recruited at different setting s , regarding their knowledge about the effectiveness of , resistance toward , and self medications with antibiotics against bacterial , viral and parasitic diseases . 67.1 % believed that antibiotics treat common cold and cough . 28.1 % misused antibiotics as analgesics . 11.9 % of females showed inadequate knowledge about the safe use of antibiotics during pregnancy and nursing . 28.5 % kept antibiotics at home for emergency use and 55.6 % use them as prophylaxis against infections . 49.0 % use left-over antibiotics without physicians ' consultation while 51.8 % use antibiotics based on a relative advice . 22.9 % of physicians prescribe antibiotics over the phone and > 50.0 % routinely prescribe antibiotics to treat common cold symptoms . Our findings indicated that young adults showed unsatisfactory knowledge of proper antibiotic use . Therefore , there is an urge for educational programs using all media means |
12,889 | 32,275,982 | The ELF test showed high sensitivity but limited specificity to exclude advanced and significant fibrosis at low cutoffs . | BACKGROUND AND AIMS The Enhanced Liver Fibrosis ( ELF ) test is a non-invasive biomarker , suggested as an appropriate test for advanced liver fibrosis in non-alcoholic fatty liver disease ( NAFLD ) .
This systematic review aim ed to provide summary estimates of the accuracy of this test against biopsy . | Background Morbid obese patients have a high rate of nonalcoholic fatty liver disease ( NAFLD ) and nonalcoholic steatohepatitis ( NASH ) . NASH is related to the progression and poor evolution of chronic hepatopathy in NAFLD , so that its detection makes it possible to identify the subjects who are most at risk in order to prioritize treatment . The ELF test ( Enhanced Liver Fibrosis test ; Siemens Diagnostics , NY , USA ) has been assessed for its capacity to detect fibrosis in patients with NAFLD , but its capacity for diagnosing NASH has not been checked . Aims Our objective is to determine the utility of the ELF test for detecting NASH in morbid obese patients with suspected NAFLD . Methods ELF values were determined in a cohort of obese patients who underwent bariatric surgery with suspected NAFLD . Liver biopsy was used as the reference st and ard . Results The values of ELF were significantly higher in patients with NASH ( p = 0.002 ) and in those who presented with metabolic syndrome ( p = 0.047 ) . An ELF cut-off point of 8.72 allows the detection of patients with NASH with a sensitivity of 71.4 % and a specificity of 74.1 % ( AUC = 0.742 , p = 0.002 ) . Conclusions The ELF test is efficient for the identification of obese patients with NAFLD and early signs of steatohepatitis and fibrosis Background Liver fibrosis is the main determinant and predictor of the clinical course of nonalcoholic fatty liver disease ( NAFLD ) . To date , a liver biopsy is still considered the gold st and ard for staging fibrosis . The aim of this study was to investigate the diagnostic accuracy of the commercial enhanced liver fibrosis ( ELF ) test manufacturer 's cutoff value ( ≥9.8 ) in identifying severe fibrosis for adult patients with histologically confirmed NAFLD . Methods We tested the ELF test in a clinical practice , prospect i ve cohort of 82 consecutive patients who consecutively underwent percutaneous liver biopsy . Results All stages of liver fibrosis were represented in our cohort , and severe fibrosis was present in 15 of 82 patients ( 18.3 % ) . The stage of fibrosis was significantly associated with ELF score ( Spearman 's rho = 0.483 , p<0.001 ) . The commercial ELF test manufacturer 's cutoff identified severe fibrosis with good sensitivity ( 86.7 % ; 95 % confidence interval [ 95 % CI ] , 0.69 - 1.04 ) and high specificity ( 92.5 % ; 95 % CI , 0.86 - 0.99 ) , with a positive predictive value of 72 % and negative predictive value of 97 % . Conclusions Our data could support the use of the ELF test in clinical practice BACKGROUND & AIMS Histologic examination of a liver biopsy specimen is regarded as the reference st and ard for detecting liver fibrosis . Biopsy can be painful and hazardous , and assessment is subjective and prone to sampling error . We developed a panel of sensitive automated immunoassays to detect matrix constituents and mediators of matrix remodeling in serum to evaluate their performance in the detection of liver fibrosis . METHODS In an international multicenter cohort study , serum levels of 9 surrogate markers of liver fibrosis were compared with fibrosis stage in liver biopsy specimens obtained from 1021 subjects with chronic liver disease . Discriminant analysis of a test set of sample s was used to identify an algorithm combining age , hyaluronic acid , amino-terminal propeptide of type III collagen , and tissue inhibitor of matrix metalloproteinase 1 that was subsequently evaluated using a validation set of biopsy specimens and serum sample s. RESULTS The algorithm detected fibrosis ( sensitivity , 90 % ) and accurately detected the absence of fibrosis ( negative predictive value for significant fibrosis , 92 % ; area under the curve of a receiver operating characteristic plot , .804 ; st and ard error , .02 ; P < .0001 ; 95 % confidence interval , .758-.851 ) . Performance was excellent for alcoholic liver disease and nonalcoholic fatty liver disease . The algorithm performed equally well in comparison with each of the pathologists . In contrast , pathologists ' agreement over histologic scores ranged from very good to moderate ( kappa = .97-.46 ) . CONCLUSIONS Assessment of liver fibrosis with multiple serum markers used in combination is sensitive , specific , and reproducible , suggesting they may be used in conjunction with liver biopsy to assess a range of chronic liver diseases Background and Aims Liver stiffness measurement ( LSM ) and FibroTest ( FT ) are frequently used as non-invasive alternatives for fibrosis staging to liver biopsy . However , to date , diagnostic performances of Enhanced Liver Fibrosis ( ELF ) test , which consists of hyaluronic acid , aminoterminal propeptide of procollagen type-III , and tissue inhibitor of matrix metalloproteinases-1 , have not been compared to those of LSM and FT in Asian chronic hepatitis B ( CHB ) patients . Methods Between June 2010 and November 2011 , we prospect ively enrolled 170 CHB patients who underwent liver biopsies along with LSM , FT , and ELF . The Batts system was used to assess fibrosis stages . Results Areas under receiver operating characteristic curves ( AUROCs ) to predict significant fibrosis ( F≥2 ) , advanced fibrosis ( F≥3 ) , and cirrhosis ( F = 4 ) were 0.901 , 0.860 , and 0.862 for ELF , respectively ; 0.937 , 0.956 , and 0.963 for LSM ; and 0.896 , 0.921 , and 0.881 for FT . AUROCs to predict F≥2 were similar between each other , whereas LSM and FT had better AUROCs than ELF for predicting F≥3 ( both p<0.05 ) , and LSM predicted F4 more accurately than ELF ( p<0.05 ) . Optimized cutoffs of ELF to maximize sum of sensitivity and specificity were 8.5 , 9.4 , and 10.1 for F≥2 , F≥3 , and F = 4 , respectively . Using suggested ELF , LSM and FT cutoffs to diagnose F1 , F2 , F3 , and F4 , 91 ( 53.5 % ) , 117 ( 68.8 % ) , and 110 ( 64.7 % ) patients , respectively , were correctly classified according to histological results . Conclusions ELF demonstrated considerable diagnostic value in fibrosis staging in Asian CHB patients , especially in predicting F≥2 . However , LSM consistently provided better performance for predicting F≥3 and F4 Background and Aim Detection of advanced fibrosis ( F3-F4 ) in nonalcoholic fatty liver disease ( NAFLD ) is important for ascertaining prognosis . Serum markers have been proposed as alternatives to biopsy . We attempted to develop a novel algorithm for detection of advanced fibrosis based on a more efficient combination of serological markers and to compare this with established algorithms . Methods We included 158 patients with biopsy-proven NAFLD . Of these , 38 had advanced fibrosis . The following fibrosis algorithms were calculated : NAFLD fibrosis score , BARD , NIKEI , NASH-CRN regression score , APRI , FIB-4 , King´s score , GUCI , Lok index , Forns score , and ELF . Study population was r and omly divided in a training and a validation group . A multiple logistic regression analysis using bootstrapping methods was applied to the training group . Among many variables analyzed age , fasting glucose , hyaluronic acid and AST were included , and a model ( LINKI-1 ) for predicting advanced fibrosis was created . Moreover , these variables were combined with platelet count in a mathematical way exaggerating the opposing effects , and alternative models ( LINKI-2 ) were also created . Models were compared using area under the receiver operator characteristic curves ( AUROC ) . Results Of established algorithms FIB-4 and King´s score had the best diagnostic accuracy with AUROCs 0.84 and 0.83 , respectively . Higher accuracy was achieved with the novel LINKI algorithms . AUROCs in the total cohort for LINKI-1 was 0.91 and for LINKI-2 models 0.89 . Conclusion The LINKI algorithms for detection of advanced fibrosis in NAFLD showed better accuracy than established algorithms and should be vali date d in further studies including larger cohorts BACKGROUND & AIMS In nonalcoholic fatty liver disease ( NAFLD ) , the distinction between steatosis and steatohepatitis ( NASH ) and the assessment of the severity of the disease rely on liver histology alone . The aim of this study was to assess the sampling error of liver biopsy and its impact on the diagnosis and staging of NASH . METHODS Fifty-one patients with NAFLD underwent percutaneous liver biopsy with 2 sample s collected . The agreement between paired biopsy specimens was assessed by the percentage of discordant results and by the kappa reliability test . RESULTS No features displayed high agreement ; substantial agreement was only seen for steatosis grade ; moderate agreement for hepatocyte ballooning and perisinusoidal fibrosis ; fair agreement for Mallory bodies ; acidophilic bodies and lobular inflammation displayed only slight agreement . Overall , the discordance rate for the presence of hepatocyte ballooning was 18 % , and ballooning would have been missed in 24 % of patients had only 1 biopsy been performed . The negative predictive value of a single biopsy for the diagnosis of NASH was at best 0.74 . Discordance of 1 stage or more was 41 % . Six of 17 patients with bridging fibrosis ( 35 % ) on 1 sample had only mild or no fibrosis on the other and therefore could have been under staged with only 1 biopsy . Intraobserver variability was systematic ally lower than sampling variability and therefore could not account for most of the sampling error . CONCLUSIONS Histologic lesions of NASH are unevenly distributed throughout the liver parenchyma ; therefore , sampling error of liver biopsy can result in substantial misdiagnosis and staging inaccuracies The main aim of this study was the comparative evaluation of nonalcoholic fatty liver disease ( NAFLD ) fibrosis score ( NFS ) , fibrosis 4 index ( FIB-4 ) , AST-to-Platelet Ratio Index ( APRI ) , and enhanced liver fibrosis ( ELF ) test in distinguishing none/early ( F0/F1 ) from significant/advanced ( F2/F3 ) fibrosis in NAFLD patients , thereby providing an external validation cohort . Thirty-one patients with biopsy-proven NAFLD and 10 matched controls without NAFLD were prospect ively enrolled . Serum hyaluronic acid ( HA ) , aminoterminal propeptide of type III procollagen ( PIIINP ) , tissue inhibitor of metallo-proteinases (TIMP)-1 , and biochemical tests were measured . NFS , FIB-4 , APRI , and ELF were calculated . ELF , FIB-4 , and APRI , but not NFS , were higher in F2/F3 than F0/F1 group . Specifically , ELF [ area under the ROC curve ( AUROC ) : 0.86±0.10 ; p=0.004 ) and APRI ( AUROC : 0.86±0.07 ; p=0.005 ] , but not NFS ( AUROC : 0.68±0.12 ; p=0.16 ) , and FIB-4 ( AUROC : 0.71±0.11 ; p=0.10 ) , could similarly discriminate F0/F1 from F2/F3 stage . The sensitivity , specificity , positive predicted value ( PPV ) , and negative predicted value ( NPV ) were : a ) for cut-off of APRI=0.5 , 85.7 % , 70.8 % , 46.2 % , and 94.4 % , respectively , and b ) for cut-off of ELF=9.0 , 85.7 % , 83.3 % , 60.0 % , and 95.2 % , respectively . When ln(PIIINP ) or TIMP-1 were combined with APRI , the combined AUROCs could distinguish F2/F3 from F0/F1 , but without significantly higher accuracy compared with APRI alone . APRI could also distinguish patients with simple steatosis from nonalcoholic steatohepatitis , and those with from those without lobular inflammation and ballooning , findings warranting further research . In conclusions : The application of ELF test and APRI can distinguish F0/F1 from F2/F3 fibrosis stages in NAFLD patients BACKGROUND & AIMS The development of non-invasive liver fibrosis tests may enable earlier identification of patients with non-alcoholic fatty liver disease ( NAFLD ) requiring referral to secondary care . We developed and evaluated a pathway for the management of patients with NAFLD , aim ed at improving the detection of cases of advanced fibrosis and cirrhosis , and avoiding unnecessary referrals . METHODS This was a prospect i ve longitudinal cohort study , with analyses performed before and after introduction of the pathway , and comparisons made to unexposed controls . We used a 2-step algorithm combining the use of Fibrosis-4 score followed by the ELF ™ test if required . RESULTS In total , 3,012 patients were analysed . Use of the pathway detected 5 times more cases of advanced fibrosis ( Kleiner F3 ) and cirrhosis ( odds ratio [OR]5.18;95%CI2.97 - 9.04 ; p < 0.0001 ) , while reducing unnecessary referrals from primary care to secondary care by 81 % ( OR0.193 ; 95%CI 0.111 - 0.337 ; p < 0.0001 ) . Although it was used for only 48 % of referrals , significant benefits were observed in practice s exposed to the pathway compared to those which were not , with unnecessary referrals falling by 77 % ( OR0.23 ; 95 % CI0.658 - 0.082 ; p = 0.006 ) and a 4-fold improvement in detection of cases of advanced fibrosis and cirrhosis ( OR4.32 ; 95 % CI1.52 - 12.25 ; p = 0.006 ) . Compared to referrals made before the introduction of the pathway , unnecessary referrals fell from 79/83 referrals ( 95.2 % ) to 107/152 ( 70.4 % ) , representing an 88 % reduction in unnecessary referrals when the pathway was followed ( OR0.12 ; 95%CI0.042 - 0.349 ; p < 0.0001 ) . CONCLUSIONS The use of non-invasive blood tests for liver fibrosis improves the detection of advanced fibrosis and cirrhosis , while reducing unnecessary referrals in patients with NAFLD . This strategy improves re source use and benefits patients . LAY SUMMARY Non-alcoholic fatty liver disease effects up to 30 % of the population but only a minority of cases develop liver disease . Our study has shown that established blood tests can be used in primary care to stratify patients with fatty liver disease , leading to a reduction in unnecessary referrals by 80 % and greatly improving the detection of cases of advanced fibrosis and cirrhosis BACKGROUND & AIMS Advanced liver fibrosis is an important diagnostic target in non-alcoholic fatty liver disease ( NAFLD ) as it defines the subgroup of patients with impaired prognosis . The non-invasive diagnosis of advanced fibrosis is currently limited by the suboptimal positive predictive value and the grey zone ( representing indeterminate diagnosis ) of fibrosis tests . Here , we aim ed to determine the best combination of non-invasive tests for the diagnosis of advanced fibrosis in NAFLD . METHODS A total of 938 patients with biopsy-proven NAFLD were r and omized 2:1 into derivation and validation sets . All patients underwent liver stiffness measurement with vibration controlled transient elastography ( VCTE ) and blood fibrosis tests ( NAFLD fibrosis score , Fibrosis-4 [ FIB4 ] , Fibrotest , Hepascore , FibroMeter ) . FibroMeterVCTE , which combines VCTE results and FibroMeter markers in a single test , was also calculated in all patients . RESULTS For the diagnosis of advanced fibrosis , VCTE was significantly more accurate than the blood tests ( area under the receiver operating characteristic curve [ AUROC ] : 0.840 ± 0.013 , p ≤0.005 ) . FibroMeter was the most accurate blood test ( AUROC : 0.793 ± 0.015 , p ≤0.017 ) . The combinatory test FibroMeterVCTE outperformed VCTE and blood tests ( AUROC : 0.866 ± 0.012 , p ≤0.005 ) . The sequential combination of FIB4 then FibroMeterVCTE ( FIB4-FMVCTE algorithm ) or VCTE then FibroMeterVCTE ( VCTE-FMVCTE algorithm ) provided an excellent diagnostic accuracy of 90 % for advanced fibrosis , with liver biopsy only required to confirm the diagnosis in 20 % of cases . The FIB4-FMVCTE and VCTE-FMVCTE algorithms were significantly more accurate than the pragmatic algorithms currently proposed . CONCLUSION The sequential combination of fibrosis tests in the FIB4-FMVCTE and VCTE-FMVCTE algorithms provides a highly accurate solution for the diagnosis of advanced fibrosis in NAFLD . These algorithms should now be vali date d for the diagnosis of advanced liver fibrosis in diabetology or primary care setting s. LAY SUMMARY The evaluation of liver fibrosis is m and atory in non-alcoholic fatty liver disease ( NAFLD ) , as advanced fibrosis identifies the subgroup of patients with impaired prognosis . FibroMeterVCTE is a new fibrosis test combining blood markers and the result of vibration controlled transient elastography ( VCTE ) into a single diagnostic test . Our results show that FibroMeterVCTE outperforms other blood fibrosis tests and VCTE alone for the diagnosis of advanced fibrosis in a large multi-centric cohort of 938 patients with biopsy-proven NAFLD . Sequential algorithms using a simple blood test or VCTE as a first-line procedure , then FibroMeterVCTE as a second-line test accurately classified 90 % of patients |
12,890 | 25,228,553 | Data are insufficient to recommend a pediatric or an adult approach for AYAs with diffuse large B-cell lymphoma and anaplastic large cell lymphoma .
Dose-adjusted EPOCH-R seems to be a promising , radiation-free approach for AYAs with primary mediastinal B-cell lymphoma . | Adolescents and young adults ( AYAs ) with cancer have inferior survival as compared to children .
The reasons for this survival gap are multifactorial and related to psychosocial aspects , patient- and disease-related biological characteristics as well as to therapeutic approaches within this age span .
Non-Hodgkin 's lymphoma ( NHL ) comprises approximately 7 % of cancer among AYAs , and patient allocation and therapy vary between health systems .
In this systematic review we focus on the current biological and clinical knowledge relevant to AYAs with NHL applying these data to the clinical approach and practice . | PURPOSE The Pediatric Oncology Group adopted a histology-based approach to non-Hodgkin 's lymphoma and treated patients with advanced large-cell lymphoma on a separate protocol ( doxorubicin , vincristine , prednisone , 6-mercaptopurin , and methotrexate ; APO regimen ) . In this study , we assessed the effects of an intense antimetabolite therapy alternating with APO on overall survival ( OS ) and event-free survival ( EFS ) and looked into biologic correlates . PATIENTS AND METHODS From December 1994 to April 2000 , we enrolled 180 eligible pediatric patients with stage III/IV large-cell lymphoma ( LCL ) ; 90 patients were r and omly assigned to the intermediate-dose methotrexate ( IDM ) and high-dose cytarabine ( HiDAC ) arm , 85 patients to the APO arm , and five patients directly to the APO arm by study design due to CNS involvement . Planned therapy duration was 12 months . RESULTS The 4-year EFS for all patients was 67.4 % ( SE , 4.2 % ) , and OS was 80.1 % ( SE , 3.6 % ) without any significant difference between the two arms . The 4-year EFS and OS were 71.8 % ( SE , 6.1 % ) and 88.1 % ( SE , 4.4 % ) , respectively , for patients with anaplastic large-cell lymphoma , and 63.8 % ( SE , 10.3 % ) and 70.3 % ( SE , 9.0 % ) , respectively , for patients with diffuse large B-cell lymphoma . Only 11 patients required radiation ( due to unresponsive bulky disease or CNS involvement ) . The IDM/HiDAC arm was associated with more toxicity . CONCLUSION The efficacy of incorporating IDM/HiDAC in the treatment plan of pediatric and adolescent patients with advanced-stage LCL was inconclusive as to its effect on EFS , regardless of the lymphoma phenotype . It can not be excluded that with a higher number of patients , one treatment could prove superior and future studies will build on these data BACKGROUND AND OBJECTIVES This multinational retrospective study compares the outcomes of patients with primary mediastinal large B-cell lymphoma ( PMLBCL ) with sclerosis after first-generation ( dose-intensive regimens ) , third-generation ( alternating regimens ) and high-dose chemotherapy strategies , frequently with adjuvant radiation therapy . DESIGN AND METHODS Between August 1981 and December 1999 , a total of 426 previously untreated patients with confirmed diagnosis were enrolled in 20 institutions to receive combination chemotherapy with either first generation ( CHOP or CHOP-like ) regimens , third generation ( MACOP-B , VACOP-B , ProMACE CytaBOM ) regimens or high-dose chemotherapy ( HDS/ABMT ) . RESULTS With chemotherapy , complete response ( CR ) rates were 49 % ( 50/105 ) , 51 % ( 142/277 ) and 53 % ( 23/44 ) with first generation , third generation and high-dose chemotherapy strategies , respectively ; partial response ( PR ) rates were 32 % , 36 % and 35 % , respectively . All patients who achieved CR and 124/142 ( 84 % ) with PR had radiation therapy on the mediastinum . The final CR rates became 61 % for CHOP/CHOP-like regimens , 79 % for MACOP-B and other regimens , and 75 % for HDS/ABMT . After median follow-ups from attaining CR of 48.5 months for CHOP/CHOP-like regimens , 51.7 months for MACOP-B type regimens and 32.4 months for HDS/ABMT , relapses occurred in 15/64 ( 23 % ) , 27/218 ( 12 % ) and 0/33 ( 0 % ) patients , respectively . Projected 10-year progression-free survival rates were 35 % , 67 % and 78 % , respectively ( p=0.0000 ) . Projected 10-year overall survival rates were 44 % , 71 % and 77 % , respectively ( p=0.0000 ) , after median follow-ups from diagnosis of 52.3 months , 54.9 months and 35.8 months , respectively . INTERPRETATION AND CONCLUSIONS In patients with PMLBCL with sclerosis , MACOP-B plus radiation therapy may be a better strategy than other treatments ; these retrospective data need to be confirmed by prospect i ve studies . The encouraging survival results after high dose chemotherapy require confirmation in selected high-risk patients BACKGROUND Cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) is used to treat patients with non-Hodgkin lymphoma . Interval decrease from 3 weeks of treatment ( CHOP-21 ) to 2 weeks ( CHOP-14 ) , and addition of rituximab to CHOP-21 ( R-CHOP-21 ) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma ( DLBCL ) . This r and omised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14 . METHODS 1222 elderly patients ( aged 61 - 80 years ) were r and omly assigned to six or eight cycles of CHOP-14 with or without rituximab . Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement . The primary endpoint was event-free survival ; secondary endpoints were response , progression during treatment , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat . The trial is registered on National Cancer Institute website , number NCT00052936 and as EU-20243 . FINDINGS 3-year event-free survival was 47.2 % after six cycles of CHOP-14 ( 95 % CI 41.2 - 53.3 ) , 53.0 % ( 47.0 - 59.1 ) after eight cycles of CHOP-14 , 66.5 % ( 60.9 - 72.0 ) after six cycles of R-CHOP-14 , and 63.1 % ( 57.4 - 68.8 ) after eight cycles of R-CHOP-14 . Compared with six cycles of CHOP-14 , the improvement in 3-year event-free survival was 5.8 % ( -2.8 - 14.4 ) for eight cycles of CHOP-14 , 19.3 % ( 11.1 - 27.5 ) for six cycles of R-CHOP-14 , and 15.9 % ( 7.6 - 24.2 ) for eight cycles of R-CHOP-14 . 3-year overall survival was 67.7 % ( 62.0 - 73.5 ) for six cycles of CHOP-14 , 66.0 % ( 60.1 - 71.9 ) for eight cycles of CHOP-14 , 78.1 % ( 73.2 - 83.0 ) for six cycles of R-CHOP-14 , and 72.5 % ( 67.1 - 77.9 ) for eight cycles of R-CHOP-14 . Compared with treatment with six cycles of CHOP-14 , overall survival improved by -1.7 % ( -10.0 - 6.6 ) after eight cycles of CHOP-14 , 10.4 % ( 2.8 - 18.0 ) after six cycles of R-CHOP-14 , and 4.8 % ( -3.1 - 12.7 ) after eight cycles of R-CHOP-14 . In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference , and adjusting for known prognostic factors , all three intensified regimens improved 3-year event-free survival ( eight cycles of CHOP-14 : RR [ relative risk ] 0.76 [ 0.60 - 0.95 ] , p=0.0172 ; six cycles of R-CHOP-14 : RR 0.51 [ 0.40 - 0.65 ] , p<0.0001 ; eight cycles of R-CHOP-14 : RR 0.54 [ 0.43 - 0.69 ] , p<0.0001 ) . Progression-free survival improved after six cycles of R-CHOP-14 ( RR 0.50 [ 0.38 - 0.67 ] , p<0.0001 ) , and eight cycles of R-CHOP-14 ( RR 0.59 [ 0.45 - 0.77 ] , p=0.0001 ) . Overall survival improved only after six cycles of R-CHOP-14 ( RR 0.63 [ 0.46 - 0.85 ] , p=0.0031 ) . In patients with a partial response after four cycles of chemotherapy , eight cycles were not better than six cycles . INTERPRETATION Six cycles of R-CHOP-14 significantly improved event-free , progression-free , and overall survival over six cycles of CHOP-14 treatment . Response-adapted addition of chemotherapy beyond six cycles , though widely practice d , is not justified . Of the four regimens assessed in this study , six cycles of R-CHOP-14 is the preferred treatment for elderly patients , with which other approaches should be compared BACKGROUND The role of rituximab in combination with different CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like chemotherapy regimens in young patients with good-prognosis diffuse large-B-cell lymphoma remains to be defined . We aim ed to compare CHOP-like chemotherapy and rituximab with CHOP-like chemotherapy alone in these patients . METHODS 824 patients who were from 18 countries ; aged 18 - 60 years ; and who had no risk factors or one risk factor according to age-adjusted International Prognostic Index ( IPI ) , stage II-IV disease , or stage I disease with bulk were enrolled . These patients were r and omly assigned to six cycles of CHOP-like chemotherapy and rituximab ( n=413 ) or to six cycles of CHOP-like chemotherapy alone ( n=411 ) . Bulky and extranodal sites received additional radiotherapy . The primary endpoint was event-free survival ; secondary endpoints were response , progression under therapy , progression-free survival , overall survival , and frequency of toxic effects . Analyses were done by intention to treat and per protocol . This trial is registered at http://www . clinical trials.gov , NCT 00064116 . FINDINGS After a median follow-up of 34 months ( range 0.03 - 61 ) , patients assigned chemotherapy and rituximab had increased 3-year event-free survival compared with those assigned chemotherapy alone ( 79 % [ 95 % CI 75 - 83 ] vs 59 % [ 54 - 64 ] ; difference between groups 20 % [ 13 - 27 ] , log-rank p<0.0001 ) , and had increased 3-year overall survival ( 93 % [ 90 - 95 ] vs 84 % [ 80 - 88 ] ; difference between groups 9 % [ 3 - 13 ] , log-rank p=0.0001 ) . Event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI : after chemotherapy and rituximab , a favourable subgroup ( ie , IPI=0 , no bulk ) could be defined from a less-favourable subgroup ( ie , IPI=1 or bulk , or both ) . Groups did not differ in the frequency of adverse events . INTERPRETATION Rituximab added to six cycles of CHOP is an effective treatment for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows for a more refined therapeutic approach for these patients Background A phase II trial of dose-adjusted etoposide , prednisone , vincristine , cyclophosphamide , doxorubicin and rituximab ( DA-EPOCH-R ) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma . The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting . Design and Methods The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II . Radiaton therapy was not permitted on study . Median age was 58 years ( range 23–83 ) and 40 % had high-intermediate or high International Prognostic Index risk . Immunohistochemical biomarkers for cell of origin and proliferation were performed . Results With a median follow up of 62 months , time to progression and overall survival were 81 % and 84 % , respectively , and time to progression was 87 % , 92 % and 54 % for low/low-intermediate , high-intermediate and high International Prognostic Index risk groups , respectively , at 5-years and beyond . The time to progression and event-free survival of germinal center B-cell lymphoma were 100 % and 94 % , respectively , and non-germinal center B-cell GCB diffuse large B-cell lymphoma were 67 % and 58 % , respectively , at 62 months ( germinal center vs. non-germinal center B cell P=0.008 ) . DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities . Conclusions These results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes . The trial was registered at Clinical Trials . Gov ( NCT00032019 ) The purpose of this study was ( 1 ) to investigate the efficacy of chemotherapy regimens design ed by the French Society of Pediatric Oncology for childhood anaplastic large-cell lymphoma ( ALCL ) and ( 2 ) to identify prognostic factors in these children . Eighty-two children with newly diagnosed ALCL were enrolled in two consecutive studies , HM89 and HM91 . The diagnosis of ALCL was based on immuno-morphological features and all the cases but 2 were investigated using ALK1 antibody directed to the NPM/ALK protein associated with the 2;5 translocation . Treatment consisted of 2 courses of COPADM ( methotrexate , cyclophosphamide , doxorubicin , vincristine , and prednisone ) and a maintenance treatment of 5 to 7 months . Seventy-eight patients ( 95 % ) achieved a complete remission and 21 relapsed . The probability of survival and event-free survival at 3 years was of 83 % ( 72 % to 90 % ) and 66 % ( 54 % to 76 % ) , respectively , with a median follow-up of 49 months . In multivariate analysis , visceral involvement , mediastinal involvement , and lacticodeshydrogenase ( LDH ) level > /=800 UI/L were shown to be predictive of a higher risk of failure . In conclusion , this type of regimen demonstrated efficacy in childhood ALCL . However , therapeutic results have to be improved for children with adverse prognostic parameters such as visceral or mediastinal involvement or a high LDH level The prognosis for higher risk childhood B-cell non-Hodgkin lymphoma has improved over the past 20 years but the optimal intensity of treatment has yet to be determined . Children 21 years old or younger with newly diagnosed B-cell non-Hodgkin lymphoma/B-cell acute lymphoblastic leukemia ( B-NHL/B-ALL ) with higher risk factors ( bone marrow [ BM ] with or without CNS involvement ) were r and omized to st and ard intensity French-American-British/Lymphoma Malignancy B ( FAB/LMB ) therapy or reduced intensity ( reduced cytarabine plus etoposide and deletion of 3 maintenance courses M2 , M3 , M4 ) . All patients with CNS disease had additional high-dose methotrexate ( 8 g/m2 ) plus extra intrathecal therapy . Fifty-one percent had BM involvement , 20 % had CNS involvement , and 29 % had BM and CNS involvement . One hundred ninety patients were r and omized . The probabilities of 4-year event-free survival ( EFS ) and survival ( S ) were 79 % + /- 2.7 % and 82 % + /- 2.6 % , respectively . In patients in remission after 3 cycles who were r and omized to st and ard versus reduced-intensity therapy , the 4-year EFS after r and omization was 90 % + /- 3.1 % versus 80 % + /- 4.2 % ( one-sided P = .064 ) and S was 93 % + /- 2.7 % versus 83 % + /- 4.0 % ( one-sided P = .032 ) . Patients with either combined BM/CNS disease at diagnosis or poor response to cyclophosphamide , Oncovin [ vincristine ] , prednisone ( COP ) reduction therapy had a significantly inferior EFS and S ( P < .001 ) . St and ard-intensity FAB/LMB therapy is recommended for children with high-risk B-NHL ( B-ALL with or without CNS involvement ) PURPOSE To prove prospect ively the efficacy of a short-pulse chemotherapy for treatment of Ki-1 anaplastic large-cell lymphoma ( ALCL ) of childhood . PATIENTS AND METHODS From October 1983 to December 1992 , 62 patients ( median age , 9.7 years ) with newly diagnosed Ki-1 ALCL were enrolled onto Non-Hodgkin 's Lymphoma-Berlin-Frankfurt-Munster ( NHL-BFM ) studies 83 , 86 , and 90 . The most frequent immunophenotype was T cell . Ki-1 ALCL differed from other subsets of NHL of childhood by the more frequent involvement of bone , soft tissue , and skin , and by the lack of bone marrow ( BM ) disease . A 5-day prephase course ( prednisone/cyclophosphamide ) was followed by two different 5-day courses of chemotherapy : course A consisted of dexamethasone , methotrexate ( MTX ) 0.5 g/m2 ( 24-hour infusion ) , intrathecal chemotherapy , ifosfamide , cytarabine ( Ara-C ) , and etoposide ( VP-16 ) ; course B consisted of cyclophosphamide and doxorubicin instead of ifosfamide , and Ara-C/VP-16 , respectively . Treatment was stratified into three branches . Branch 1 ( stage I and stage II resected ) received three courses ; branch 2 ( stage II not resected , stage III ) , six courses ; and branch 3 ( stage IV ) , six intensified courses containing MTX 5 g/m2 , and Ara-C 2 g/m2 . Local radiotherapy was not performed . RESULTS Four patients failed to enter remission , and one died of infection . Seven patients relapsed within 9 months after diagnosis ; two patients had isolated local relapses , but BM and CNS were never involved . Fifty patients have been in first continuous complete remission ( CR ) for 0.6 to 9.7 years ( median , 2.5 ) , and 56 are alive . The probabilities for survival and event-free survival ( EFS ) at 9 years are 83 % + /- 7 % ( SE ) and 81 % + /- 5 % . Skin involvement was the only negative prognostic parameter . CONCLUSION Short-pulse chemotherapy over 2 to 5 months without local therapy modalities is effective in the treatment of Ki-1 ALCL A previous study ( LMB89 ) of the French Society of Pediatric Oncology for childhood mature B-cell lymphoma ( B-NHL ) demonstrated a 92 % 3-year event-free survival ( EFS ) for intermediate-risk group B defined as " non-resected " stage II/I and CNS-negative advanced-stage IIV/IV ( 70 % of cases ) . We performed the FAB/LMB96 trial to assess the possibility of reducing treatment in children/adolescents with intermediate-risk B-NHL without jeopardizing survival . " Early responding " patients ( tumor response > 20 % at day 7 ) were r and omized in a factorial design between 4 arms , 2 receiving half-dose of cyclophosphamide in the second induction course with cyclophosphamide , Oncovin ( vincristine ) , prednisone , Adriamycin ( doxorubicin ) , methotrexate ( COPADM ) and 2 not receiving the maintenance course M1 . A total of 657 patients were r and omized ( May 1996 to June 2001 ) and 637 were analyzed . The analysis showed no significant effect of any of the treatment reductions on EFS and survival . The 4-year EFS was 93.4 % and 90.9 % in the groups with full-dose and half-dose of cyclophosphamide ( RR = 1.3 , P = .40 ) and 91.9 % and 92.5 % in the groups with and without M1 ( RR = 1.01 , P = .98 ) . There was no interaction between the 2 treatment reductions or between each treatment reduction and LDH level or histologic subtypes ( Burkitt/Burkitt-like or large B-cell ) . Children/adolescents with intermediate-risk B-NHL who have an early response and achieve a complete remission after the first consolidation course can be cured with a 4-course treatment with a total dose of only 3.3 g/m2 cyclophosphamide and 120 mg/m2 doxorubicin Imatinib mesylate , an inhibitor of the Bcr-Abl tyrosine kinase , has modest activity in refractory/relapsed Philadelphia chromosome (Ph)-positive acute lymphocytic leukemia ( ALL ) . Use of concurrent chemotherapy and imatinib mesylate in newly diagnosed Ph-positive ALL was explored . There were 20 patients who received hyper-CVAD ( cyclophosphamide , vincristine , Adriamycin , and dexamethasone ) and imatinib mesylate followed by imatinib mesylate-based consolidation/maintenance therapy . Of these patients , 11 had de novo disease , 4 were primary failures after induction ( without imatinib mesylate ) , and 5 were in complete remission ( CR ) after induction ( without imatinib mesylate ) . All 15 patients treated for active disease achieved CR . Within a median of 3.5 months in first CR , 10 patients underwent allogeneic stem cell transplantation ( SCT ) . One patient relapsed after matched related SCT . The other 9 patients remained alive in CR with median follow-up of 12 months after SCT ( range , 1 + to 17 + months ) . Among 10 patients ineligible for ( no donor or older age ) or refusing allogeneic SCT , 1 patient relapsed after one year . There were 5 patients who remained alive in continuous CR for a median of 20 months ( range , 4 + to 24 + months ) , with 2 older patients dying in CR at 15 and 16 months of comorbid conditions . Molecular CRs were achieved in both groups ( SCT or no SCT ) . Outcome with hyper-CVAD and imatinib mesylate appears better than with prior regimens ; continued accrual and longer follow-up of the current cohort is needed To study prognostic factors of progression/relapse , data concerning 225 children enrolled between 1987 and 1997 in Berlin-Frankfurt-Münster , Société Française d'Oncologie Pédiatrique and United Kingdom Children 's Cancer Study Group prospect i ve studies for the treatment of anaplastic large cell lymphoma ( ALCL ) were merged . Median follow-up was 9.3 years . Five-year overall survival and event-free survival of the whole population was 81 % ( 95 % confidence interval , 76%-86 % ) and 69 % ( 63%-74 % ) , respectively . B symptoms , mediastinal involvement , skin lesions , visceral involvement , St Jude stage 3 - 4 , Ann Arbor stage 3 - 4 , and elevated lactate dehydrogenase increased the risk of progression/relapse in the univariate analysis . In the multivariate analysis , 3 factors remained significant : mediastinal involvement ( relative risk [ RR ] = 2.1 [ 1.2 - 3.5 ] ) , visceral involvement defined as lung , liver , or spleen involvement ( RR = 2.1 [ 1.3 - 3.6 ] ) , and skin lesions ( RR = 1.9 [ 1.1 - 3.2 ] ) . Five-year progression-free survival ( PFS ) of the 81 patients with none of these risk factors was 89 % [ 82%-96 % ] , contrasting with a 5-year PFS of 61 % [ 53%-69 % ] in the 144 patients with at least 1 risk factor ( RR = 4.4 [ 2.2 - 8.9 ; P < .001 ) . In conclusion , 3 factors associated with an increased risk of failure in childhood ALCL have been defined : mediastinal involvement , visceral involvement , and skin lesions BACKGROUND Dose intensification with a combination of cyclophosphamide , doxorubicin , vincristine , and prednisolone ( CHOP ) every 2 weeks improves outcomes in patients older than 60 years with diffuse large B-cell lymphoma compared with CHOP every 3 weeks . We investigated whether this survival benefit from dose intensification persists in the presence of rituximab ( R-CHOP ) in all age groups . METHODS Patients ( aged ≥18 years ) with previously untreated bulky stage IA to stage IV diffuse large B-cell lymphoma in 119 centres in the UK were r and omly assigned central ly in a one-to-one ratio , using minimisation , to receive six cycles of R-CHOP every 14 days plus two cycles of rituximab ( R-CHOP-14 ) or eight cycles of R-CHOP every 21 days ( R-CHOP-21 ) . R-CHOP-21 was intravenous cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 1·4 mg/m(2 ) ( maximum dose 2 mg ) , and rituximab 375 mg/m(2 ) on day 1 , and oral prednisolone 40 mg/m(2 ) on days 1 - 5 , administered every 21 days for a total of eight cycles . R-CHOP-14 was intravenous cyclophosphamide 750 mg/m(2 ) , doxorubicin 50 mg/m(2 ) , vincristine 2 mg , rituximab 375 mg/m(2 ) on day 1 , and oral prednisolone 100 mg on days 1 - 5 , administered every 14 days for six cycles , followed by two further infusions of rituximab 375 mg/m(2 ) on day 1 every 14 days . The trial was not masked . The primary outcome was overall survival ( OS ) . This study is registered , number IS RCT N 16017947 . FINDINGS 1080 patients were assigned to R-CHOP-21 ( n=540 ) and R-CHOP-14 ( n=540 ) . With a median follow-up of 46 months ( IQR 35 - 57 ) , 2-year OS was 82·7 % ( 79·5 - 85·9 ) in the R-CHOP-14 group and 80·8 % ( 77·5 - 84·2 ) in the R-CHOP-21 ( st and ard ) group ( hazard ratio 0·90 , 95 % CI 0·70 - 1·15 ; p=0·3763 ) . No significant improvement was noted in 2-year progression-free survival ( R-CHOP-14 75·4 % , 71·8 - 79·1 , and R-CHOP-21 74·8 % , 71·0 - 78·4 ; 0·94 , 0·76 - 1·17 ; p=0·5907 ) . High international prognostic index , poor-prognosis molecular characteristics , and cell of origin were not predictive for benefit from either schedule . Grade 3 or 4 neutropenia was higher in the R-CHOP-21 group ( 318 [ 60 % ] of 534 vs 167 [ 31 % ] of 534 ) , with no prophylactic use of recombinant human granulocyte-colony stimulating factor m and ated in this group , whereas grade 3 or 4 thrombocytopenia was higher with R-CHOP-14 ( 50 [ 9 % ] vs 28 [ 5 % ] ) ; other frequent grade 3 or 4 adverse events were febrile neutropenia ( 58 [ 11 % ] vs 28 [ 5 % ] ) and infection ( 125 [ 23 % ] vs 96 [ 18 % ] ) . Frequencies of non-haematological adverse events were similar in the R-CHOP-21 and R-CHOP-14 groups . INTERPRETATION R-CHOP-14 is not superior to R-CHOP-21 chemotherapy for previously untreated diffuse large B-cell lymphoma ; therefore , R-CHOP-21 remains the st and ard first-line treatment in patients with this haematological malignancy . No molecular or clinical subgroup benefited from dose intensification in this study . FUNDING Chugai Pharmaceutical , Cancer Research UK , National Institute for Health Research Biomedical Research Centres scheme at both University College London and the Royal Marsden NHS Foundation Trust , and Institute of Cancer Research We hypothesized that incremental improvements in the cyclophosphamide-doxorubicin-vincristine-prednisone ( CHOP ) chemotherapy regimen through optimization of drug selection , schedule , and pharmacokinetics would improve outcome in patients with large B-cell lymphomas . A prospect i ve multi-institutional study of administration of etoposide , vincristine , and doxorubicin for 96 hours with bolus doses of cyclophosphamide and oral prednisone ( EPOCH therapy ) was done in 50 patients with previously untreated large B-cell lymphomas . The doses of etoposide , doxorubicin , and cyclophosphamide were adjusted 20 % each cycle to achieve a nadir absolute neutrophil count below 0.5 x 10(9)/L. The median age of the patients was 46 years ( range , 20 - 88 years ) ; 24 % were older than 60 years ; and 44 % were at high-intermediate or high risk according to International Prognostic Index ( IPI ) criteria . There was a complete response in 92 % of patients , and at the median follow-up time of 62 months , the progression-free survival ( PFS ) and overall survival ( OS ) rates were 70 % and 73 % , respectively . Neither IPI risk factors nor the index itself was associated with response , PFS , or OS . Doses were escalated in 58 % of cycles , and toxicity levels were tolerable . Significant inverse correlations were observed between dose intensity and age for all adjusted agents , and drug clearance of doxorubicin and free etoposide was also inversely correlated with age ( r = -0.54 and P(2 ) = .08 and r = -0.45 and P(2 ) = .034 , respectively ) . Free-etoposide clearance increased significantly during successive cycles ( P(2 ) = .015 ) . Lymphomas with proliferation of at least 80 % had somewhat lower progression and those expressing bcl-2 had significantly higher progression ( P(2 ) = .04 ) . Expression of bcl-2 may discriminate the recently described activated B-like from germinal-center B-like large-cell lymphomas and provide important pathobiologic and prognostic information . Dose-adjusted EPOCH may produce more cell kill than CHOP-based regimens . Dynamic dose adjustment may overcome inadequate drug concentrations , particularly in younger patients , and compensate for increased drug clearance over time BACKGROUND The MInT study was the first to show improved 3-year outcomes with the addition of rituximab to a CHOP ( cyclophosphamide , doxorubicin , vincristine , and prednisone)-like regimen in young patients with good-prognosis diffuse large-B-cell lymphoma . Extended follow-up was needed to establish long-term effects . METHODS In the r and omised open-label MInT study , patients from 18 countries ( aged 18 - 60 years with none or one risk factor according to the age-adjusted International Prognostic Index [ IPI ] , stage II-IV disease or stage I disease with bulk ) were r and omly assigned to receive six cycles of a CHOP-like chemotherapy with or without rituximab . Bulky and extranodal sites received additional radiotherapy . R and omisation was done central ly with a computer-based tool and was stratified by centre , bulky disease , age-adjusted IPI , and chemotherapy regimen by use of a modified minimisation algorithm that incorporated a stochastic component . Patients and investigators were not masked to treatment allocation . The primary endpoint was event-free survival . Analyses were by intention to treat . This observational study is a follow-up of the MInT trial , which was stopped in 2003 , and is registered at Clinical Trials.gov , number NCT00400907 . FINDINGS The intention-to-treat population included 410 patients assigned to chemotherapy alone and 413 assigned to chemotherapy plus rituximab . After a median follow-up of 72 months ( range 0·03 - 119 ) , 6-year event-free survival was 55·8 % ( 95 % CI 50·4 - 60·9 ; 166 events ) for patients assigned to chemotherapy alone and 74·3 % ( 69·3 - 78·6 ; 98 events ) for those assigned to chemotherapy plus rituximab ( difference between groups 18·5 % , 11·5 - 25·4 , log-rank p<0·0001 ) . Multivariable analyses showed that event-free survival was affected by treatment group , presence of bulky disease , and age-adjusted IPI and that overall survival was affected by treatment group and presence of bulky disease only . After chemotherapy and rituximab , a favourable subgroup ( IPI=0 , no bulk ) could be defined from a less favourable subgroup ( IPI=1 or bulk , or both ; event-free survival 84·3 % [ 95 % CI 74·2 - 90·7 ] vs 71·0 % [ 65·1 - 76·1 ] , log-rank p=0·005 ) . 18 ( 4·4 % , 95 % CI 2·6 - 6·9 ) second malignancies occurred in the chemotherapy-alone group and 16 ( 3·9 % , 2·2 - 6·2 ) in the chemotherapy and rituximab group ( Fisher 's exact p=0·730 ) . INTERPRETATION Rituximab added to six cycles of CHOP-like chemotherapy improved long-term outcomes for young patients with good-prognosis diffuse large-B-cell lymphoma . The definition of two prognostic subgroups allows a more refined therapeutic approach to these patients than does assessment by IPI alone . FUNDING Hoffmann-La Roche This study was undertaken to show that a high survival rate can be obtained in B-cell ( Burkitt and large B-cell ) lymphoma and L3 leukemia with multiagent chemotherapy adapted to the tumor burden ( stage , resection status , percentage of blasts in bone marrow , and central nervous system [ CNS ] involvement ) and early response to chemotherapy , to investigate actual prognostic factors , and to see if large B-cell lymphoma can be treated with the same regimen as Burkitt lymphoma . Patients were classified into 3 risk groups . Group A ( resected stage I and abdominal stage II ) received 2 courses of vincristine , cyclophosphamide , doxorubicin , and prednisone . Group B ( patients not eligible for groups A or C ) received 5 courses of chemotherapy with , in addition , high-dose methotrexate , 3 g/m(2 ) over 3 hours ; infusional cytarabine ; and intrathecal ( IT ) methotrexate . Group C ( patients with CNS involvement and acute lymphoblastic leukemia with at least 70 % of blasts in bone marrow ) received 8 courses with , in addition , high-dose methotrexate , 8 g/m(2 ) ; high-dose cytarabine ; etoposide ; and triple IT . Except in group A , treatment started with a prephase ( COP , low-dose vincristine and cyclophosphamide ) . It was intensified for patients who did not respond to COP in group B and any patient with residual viable cells after the consolidation phase . A total of 561 patients were enrolled in the SFOP LMB89 protocol ( July 1989-June 1996 ) . Five-year survival is 92.5 % ( 95 % confidence interval [ CI ] , 90%-94 % ) and event-free survival ( EFS ) 91 % ( 95 % CI , 89%-93 % ) . EFS is 98 % ( 95 % CI , 90%-100 % ) , 92 % ( 95 % CI , 89%-95 % ) , and 84 % ( 95 % CI , 77%-90 % ) for group A , B , and C , respectively . In group B , multivariate analysis of prognostic factors showed that a lactate dehydrogenase level more than 2-fold the normal value , no response after COP , and age of at least 15 years were associated with a lower EFS . CNS involvement was the only prognostic factor in group C. ( Blood . 2001;97:3370 - 3379 BACKGROUND The aim of this subgroup analysis of the Mabthera International Trial Group study was to evaluate the impact of chemotherapy and rituximab in primary mediastinal B-cell lymphoma ( PMBCL ) in comparison to other diffuse large B-cell lymphoma ( DLBCL ) . METHODS Patients were r and omly assigned to six cycles of CHOP-like regimens with or without rituximab . RESULTS Of 824 patients enrolled , 87 had PMBCL and 627 other types of DLBCL . Rituximab increased the rates of complete remission ( unconfirmed ) in both PMBCL ( from 54 % to 80 % , P = 0.015 ) and DLBCL ( from 72 % to 87 % , P < 0.001 ) . In PMBCL , rituximab virtually eliminated progressive disease ( PD ) ( 2.5 % versus 24 % , P < 0.001 ) , whereas without rituximab , PD was more frequent in PMBCL than in DLBCL ( 24 % versus 10 % , P = 0.010 ) . With a median observation time of 34 months , 3-year event-free survival ( EFS ) was improved by rituximab for PMBCL ( 78 % versus 52 % , P = 0.012 ) and for DLBCL ( 81 % versus 61 % , P < 0.001 ) . Overall survival benefit was similar for DLBCL ( 93 % versus 85 % , P < 0.001 ) and PMBCL ( 89 % versus 78 % , P = 0.158 ) . CONCLUSION In young patients with PMBCL ( age-adjusted International Prognostic Index 0 - 1 ) , rituximab added to six cycles of CHOP-like chemotherapy increases response rate and EFS to the same extent as other DLBCL . The combination of rituximab with CHOP chemotherapy is an effective treatment in PMBCL with good prognosis features Patients with peripheral T cell lymphoma ( PTCL ) have a poor prognosis with current treatment approaches . We examined the outcomes of high-dose therapy ( HDT ) and autologous hematopoietic cell transplant ( AHCT ) on the treatment of PTCL and the impact of patient/disease features on long-term outcome . Sixty-seven patients with PTCL-not otherwise specified ( n = 30 ) , anaplastic large cell lymphoma ( n = 30 ) , and angioimmunoblastic T cell lymphoma ( n = 7 ) underwent HDT/AHCT at the City of Hope . The median age was 48 years ( range : 5 - 78 ) . Twelve were transplanted in first complete remission (1CR)/partial remission ( PR ) and 55 with relapsed or induction failure disease ( RL/IF ) . With a median follow-up for surviving patients of 65.8 months ( range : 24.5 - 216.0 ) the 5-year overall survival ( OS ) and progression-free survival ( PFS ) were 54 % and 40 % , respectively . The 5-year PFS was 75 % for 1CR/PR compared to 32 % for RL/IF patients ( P = .01 ) . When the Prognostic Index for PTCL unspecified ( PIT ) was applied at the time of transplant , patients in the PIT 3 - 4 group had 5-year PFS of only 8 % . These results show that HDT/AHCT can improve long-term disease control in relapsed/refractory PTCL and that HDT/AHCT should ideally be applied either during 1CR/PR , or as part of upfront treatment . More effective and novel therapies are needed for patients with high-risk disease ( PIT 3 - 4 factors ) and allogeneic HCT should be explored in these patients BACKGROUND Various human cancers have ALK gene translocations , amplifications , or oncogenic mutations , such as anaplastic large-cell lymphoma , inflammatory myofibroblastic tumours , non-small-cell lung cancer ( NSCLC ) , and neuroblastoma . Therefore , ALK inhibition could be a useful therapeutic strategy in children . We aim ed to determine the safety , recommended phase 2 dose , and antitumour activity of crizotinib in children with refractory solid tumours and anaplastic large-cell lymphoma . METHODS In this open-label , phase 1 dose-escalation trial , patients older than 12 months and younger than 22 years with measurable or evaluable solid or CNS tumours , or anaplastic large-cell lymphoma , refractory to therapy and for whom there was no known curative treatment were eligible . Crizotinib was given twice daily without interruption . Six dose levels ( 100 , 130 , 165 , 215 , 280 , 365 mg/m(2 ) per dose ) were assessed in the dose-finding phase of the study ( part A1 ) , which is now completed . The primary endpoint was to estimate the maximum tolerated dose , to define the toxic effects of crizotinib , and to characterise the pharmacokinetics of crizotinib in children with refractory cancer . Additionally , patients with confirmed ALK translocations , mutations , or amplification ( part A2 of the study ) or neuroblastoma ( part A3 ) could enrol at one dose level lower than was currently given in part A1 . We assessed ALK genomic status in tumour tissue and used quantitative RT-PCR to measure NPM-ALK fusion transcript in bone marrow and blood sample s of patients with anaplastic large-cell lymphoma . All patients who received at least one dose of crizotinib were evaluable for response ; patients completing at least one cycle of therapy or experiencing dose limiting toxicity before that were considered fully evaluable for toxicity . This study is registered with Clinical Trials.gov , NCT00939770 . FINDINGS 79 patients were enrolled in the study from Oct 2 , 2009 , to May 31 , 2012 . The median age was 10.1 years ( range 1.1 - 21.4 ) ; 43 patients were included in the dose escalation phase ( A1 ) , 25 patients in part A2 , and 11 patients in part A3 . Crizotinib was well tolerated with a recommended phase 2 dose of 280 mg/m(2 ) twice daily . Grade 4 adverse events in cycle 1 were neutropenia ( two ) and liver enzyme elevation ( one ) . Grade 3 adverse events that occurred in more than one patient in cycle 1 were lymphopenia ( two ) , and neutropenia ( eight ) . The mean steady state peak concentration of crizotinib was 630 ng/mL and the time to reach this peak was 4 h ( range 1 - 6 ) . Objective tumour responses were documented in 14 of 79 patients ( nine complete responses , five partial responses ) ; and the anti-tumour activity was enriched in patients with known activating ALK aberrations ( eight of nine with anaplastic large-cell lymphoma , one of 11 with neuroblastoma , three of seven with inflammatory myofibroblastic tumour , and one of two with NSCLC ) . INTERPRETATION The findings suggest that a targeted inhibitor of ALK has antitumour activity in childhood malignancies harbouring ALK translocations , particularly anaplastic large-cell lymphoma and inflammatory myofibroblastic tumours , and that further investigation in the subset of neuroblastoma harbouring known ALK oncogenic mutations is warranted . FUNDING Pfizer and National Cancer Institute grant to the Children 's Oncology Group Anaplastic large-cell lymphoma ( ALCL ) accounts for approximately 10 % of pediatric non-Hodgkin lymphoma ( NHL ) . Previous experience from NHL-Berlin-Frankfurt-Münster ( BFM ) trials indicated that the short-pulse B-NHL-type treatment strategy may also be efficacious for ALCL . The purpose of this study was to test the efficacy of this protocol for treatment of childhood ALCL in a large prospect i ve multicenter trial and to define risk factors . From April 1990 to March 1995 , 89 patients younger than 18 years of age with newly diagnosed ALCL were enrolled in trial NHL-BFM 90 . Immunophenotype was T-cell in 40 patients , B-cell in 5 , null in 31 , and not determined in 13 . Stages were as follows : I , n = 8 ; II , n = 20 ; III , n = 55 ; IV , n = 6 . Extranodal manifestations were as follows : mediastinum , n = 28 ; lung , n = 13 ; skin , n = 16 ; soft tissue , n = 13 ; bone , n = 14 ; central nervous system , n = 1 ; bone marrow , n = 5 . After a cytoreductive prephase , treatment was stratified into 3 branches : patients in K1 ( stage I and II resected ) received three 5-day courses ( methotrexate [ MTX ] 0.5 g/m(2 ) , dexamethasone , oxazaphorins , etoposide , cytarabine , doxorubicin , and intrathecal therapy ) ; patients in K2 ( stage II nonresected and stage III ) received 6 courses ; patients in K3 ( stage IV or multifocal bone disease ) received 6 intensified courses including MTX 5 g/m(2 ) , high-dose cytarabine/etoposide . The Kaplan-Meier estimate for a 5-year event-free survival was 76 % + /- 5 % ( median follow-up , 5.6 years ) for all patients and 100 % , 73 % + /- 6 % , and 79 % + /- 11 % for K1 , K2 , and K3 , respectively . Events were as follows : progression during therapy , n = 2 ; progression or relapse after therapy , n = 20 ; second malignancy , n = 1 . It was concluded that short-pulse chemotherapy , stratified according to stage , is effective treatment for pediatric ALCL . B symptoms were associated with increased risk of failure . ( Blood . 2001;97:3699 - 3706 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 BACKGROUND CHOP is a first-generation , combination-chemotherapy regimen consisting of cyclophosphamide , doxorubicin , vincristine , and prednisone that has cured approximately 30 percent of patients with advanced stages of intermediate- grade or high- grade non-Hodgkin 's lymphoma in national cooperative-group trials . However , studies at single institutions have suggested that 55 to 65 percent of such patients might be cured by third-generation regimens such as ones consisting of low-dose methotrexate with leucovorin rescue , bleomycin , doxorubicin , cyclophosphamide , vincristine , and dexamethasone ( m-BACOD ) ; prednisone , doxorubicin , cyclophosphamide , and etoposide , followed by cytarabine , bleomycin , vincristine , and methotrexate with leucovorin rescue ( ProMACE-CytaBOM ) ; and methotrexate with leucovorin rescue , doxorubicin , cyclophosphamide , vincristine , prednisone , and bleomycin ( MACOP-B ) . METHODS To make a valid comparison of these regimens , the Southwest Oncology Group and the Eastern Cooperative Oncology Group initiated a prospect i ve , r and omized phase III trial . The study end points were the response rate , time to treatment failure , overall survival , and incidence of severe or life-threatening toxicity . Dose intensity was calculated and analyzed . RESULTS Of the 1138 patients registered for the trial , 899 were eligible . Each treatment group contained at least 218 patients . Known prognostic factors were equally distributed among the groups . There were no significant differences among the groups in the rates of partial and complete response . At three years , 44 percent of all patients were alive without disease ; there were no significant differences between the groups ( 41 percent in the CHOP and MACOP-B groups and 46 percent in the m-BACOD and ProMACE-CytaBOM groups ; P = 0.35 ) . Overall survival at three years was 52 percent ( 50 percent in the ProMACE-CytaBOM and MACOP-B groups , 52 percent in the m-BACOD group , and 54 percent in the CHOP group ; P = 0.90 ) . There was no subgroup of patients in which survival was improved by a third-generation regimen . Fatal toxic reactions occurred in 1 percent of the CHOP group , 3 percent of the ProMACE-CytaBOM group , 5 percent of the m-BACOD group , and 6 percent of the MACOP-B group ( P = 0.09 ) . CONCLUSIONS CHOP remains the best available treatment for patients with advanced-stage intermediate- grade or high- grade non-Hodgkin 's lymphoma BACKGROUND The outcome of diffuse large B-cell lymphoma has been substantially improved by the addition of the anti-CD20 monoclonal antibody rituximab to chemotherapy regimens . We aim ed to assess , in patients aged 18 - 59 years , the potential survival benefit provided by a dose-intensive immunochemotherapy regimen plus rituximab compared with st and ard treatment plus rituximab . METHODS We did an open-label r and omised trial comparing dose-intensive rituximab , doxorubicin , cyclophosphamide , vindesine , bleomycin , and prednisone ( R-ACVBP ) with subsequent consolidation versus st and ard rituximab , doxorubicin , cyclophosphamide , vincristine , and prednisone ( R-CHOP ) . R and om assignment was done with a computer-assisted r and omisation-allocation sequence with a block size of four . Patients were aged 18 - 59 years with untreated diffuse large B-cell lymphoma and an age-adjusted international prognostic index equal to 1 . Our primary endpoint was event-free survival . Our analyses of efficacy and safety were of the intention-to-treat population . This study is registered with Clinical Trials.gov , number NCT00140595 . FINDINGS One patient withdrew consent before treatment and 54 did not complete treatment . After a median follow-up of 44 months , our 3-year estimate of event-free survival was 81 % ( 95 % CI 75 - 86 ) in the R-ACVBP group and 67 % ( 59 - 73 ) in the R-CHOP group ( hazard ratio [ HR ] 0·56 , 95 % CI 0·38 - 0·83 ; p=0·0035 ) . 3-year estimates of progression-free survival ( 87 % [ 95 % CI , 81 - 91 ] vs 73 % [ 66 - 79 ] ; HR 0·48 [ 0·30 - 0·76 ] ; p=0·0015 ) and overall survival ( 92 % [ 87 - 95 ] vs 84 % [ 77 - 89 ] ; HR 0·44 [ 0·28 - 0·81 ] ; p=0·0071 ) were also increased in the R-ACVBP group . 82 ( 42 % ) of 196 patients in the R-ACVBP group experienced a serious adverse event compared with 28 ( 15 % ) of 183 in the R-CHOP group . Grade 3 - 4 haematological toxic effects were more common in the R-ACVBP group , with a higher proportion of patients experiencing a febrile neutropenic episode ( 38 % [ 75 of 196 ] vs 9 % [ 16 of 183 ] ) . INTERPRETATION Compared with st and ard R-CHOP , intensified immunochemotherapy with R-ACVBP significantly improves survival of patients aged 18 - 59 years with diffuse large B-cell lymphoma with low-intermediate risk according to the International Prognostic Index . Haematological toxic effects of the intensive regimen were raised but manageable . FUNDING Groupe d'Etudes des Lymphomes de l'Adulte and Amgen BACKGROUND The efficacy of autologous stem-cell transplantation during the first remission in patients with diffuse , aggressive non-Hodgkin 's lymphoma classified as high-intermediate risk or high risk on the International Prognostic Index remains controversial and is untested in the rituximab era . METHODS We treated 397 patients who had disease with an age-adjusted classification of high risk or high-intermediate risk with five cycles of cyclophosphamide , doxorubicin , vincristine , and prednisone ( CHOP ) or CHOP plus rituximab . Patients with a response were r and omly assigned to receive three additional cycles of induction chemotherapy ( control group ) or one additional cycle of induction chemotherapy followed by autologous stem-cell transplantation ( transplantation group ) . The primary efficacy end points were 2-year progression-free survival and overall survival . RESULTS Of 370 induction-eligible patients , 253 were r and omly assigned to the transplantation group ( 125 ) or the control group ( 128 ) . Forty-six patients in the transplantation group and 68 in the control group had disease progression or died , with 2-year progression-free survival rates of 69 and 55 % , respectively ( hazard ratio in the control group vs. the transplantation group , 1.72 ; 95 % confidence interval [ CI ] , 1.18 to 2.51 ; P=0.005 ) . Thirty-seven patients in the transplantation group and 47 in the control group died , with 2-year overall survival rates of 74 and 71 % , respectively ( hazard ratio , 1.26 ; 95 % CI , 0.82 to 1.94 ; P=0.30 ) . Exploratory analyses showed a differential treatment effect according to risk level for both progression-free survival ( P=0.04 for interaction ) and overall survival ( P=0.01 for interaction ) . Among high-risk patients , the 2-year overall survival rate was 82 % in the transplantation group and 64 % in the control group . CONCLUSIONS Early autologous stem-cell transplantation improved progression-free survival among patients with high-intermediate-risk or high-risk disease who had a response to induction therapy . Overall survival after transplantation was not improved , probably because of the effectiveness of salvage transplantation . ( Funded by the National Cancer Institute , Department of Health and Human Services , and others ; SWOG-9704 Clinical Trials.gov number , NCT00004031 . ) |
12,891 | 26,949,994 | Conclusions The current evidence suggests an independent and statistically significant association between increases in coronary atherosclerotic plaque burden measured by IVUS and greater long-term risk of future CVD outcomes . | Objective Evidence from coronary imaging studies suggests an association between increased atherosclerotic plaque burden and cardiovascular disease ( CVD ) outcomes .
A systematic review was performed to evaluate the relationship between coronary atherosclerotic plaque burden changes measured by intravascular ultrasound ( IVUS ) and CVD outcomes . | OBJECTIVES The purpose of this study was to characterize the determinants of plaque progression despite achieving very low levels of low-density lipoprotein cholesterol ( LDL-C ) . BACKGROUND Despite achieving very low levels of LDL-C , many patients continue to demonstrate disease progression and have clinical events . METHODS A total of 3,437 patients with coronary artery disease underwent serial intravascular ultrasound examination in 7 clinical trials . Patients who achieved an on-treatment LDL-C level of < or=70 mg/dl ( n = 951 ) were stratified as progressors ( n = 200 ) and nonprogressors ( n = 751 ) and compared . RESULTS Despite achieving LDL-C < or=70 mg/dl , > 20 % of patients continued to progress . There were no demographic differences between groups . Progressors demonstrated higher baseline levels of glucose ( 117.1 + /- 42.5 mg/dl vs. 112.1 + /- 40.0 mg/dl , p = 0.02 ) , triglycerides ( 157.5 mg/dl vs. 133.0 mg/dl , p = 0.004 ) , and a smaller decrease of apolipoprotein B ( -25.1 + /- 3.4 mg/dl vs. -27.4 + /- 3.35 mg/dl , p = 0.01 ) at follow-up . Multivariable analysis revealed that independently associated risk factors of progression in patients with LDL-C < or=70 mg/dl included baseline percent atheroma volume ( p = 0.001 ) , presence of diabetes mellitus ( p = 0.02 ) , increase in systolic blood pressure ( p = 0.001 ) , less increase in high-density lipoprotein cholesterol ( p = 0.01 ) , and a smaller decrease in apolipoprotein B levels ( p = 0.001 ) , but not changes in C-reactive protein ( p = 0.78 ) or LDL-C ( p = 0.84 ) . CONCLUSIONS Residual risk factors are associated with the likelihood of disease progression in patients who achieve very low LDL-C levels . In addition , the association between apolipoprotein B and atheroma progression highlights the potential importance of LDL particle concentration in patients with optimal LDL-C control . This finding highlights the need for intensive modification of global risk in patients with coronary artery disease CONTEXT Prior intravascular ultrasound ( IVUS ) trials have demonstrated slowing or halting of atherosclerosis progression with statin therapy but have not shown convincing evidence of regression using percent atheroma volume ( PAV ) , the most rigorous IVUS measure of disease progression and regression . OBJECTIVE To assess whether very intensive statin therapy could regress coronary atherosclerosis as determined by IVUS imaging . DESIGN AND SETTING Prospect i ve , open-label blinded end-points trial ( A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden [ ASTEROID ] ) was performed at 53 community and tertiary care centers in the United States , Canada , Europe , and Australia . A motorized IVUS pullback was used to assess coronary atheroma burden at baseline and after 24 months of treatment . Each pair of baseline and follow-up IVUS assessment s was analyzed in a blinded fashion . PATIENTS Between November 2002 and October 2003 , 507 patients had a baseline IVUS examination and received at least 1 dose of study drug . After 24 months , 349 patients had evaluable serial IVUS examinations . INTERVENTION All patients received intensive statin therapy with rosuvastatin , 40 mg/d . MAIN OUTCOME MEASURES Two primary efficacy parameters were prespecified : the change in PAV and the change in nominal atheroma volume in the 10-mm subsegment with the greatest disease severity at baseline . A secondary efficacy variable , change in normalized total atheroma volume for the entire artery , was also prespecified . RESULTS The mean ( SD ) baseline low-density lipoprotein cholesterol ( LDL-C ) level of 130.4 ( 34.3 ) mg/dL declined to 60.8 ( 20.0 ) mg/dL , a mean reduction of 53.2 % ( P<.001 ) . Mean ( SD ) high-density lipoprotein cholesterol ( HDL-C ) level at baseline was 43.1 ( 11.1 ) mg/dL , increasing to 49.0 ( 12.6 ) mg/dL , an increase of 14.7 % ( P<.001 ) . The mean ( SD ) change in PAV for the entire vessel was -0.98 % ( 3.15 % ) , with a median of -0.79 % ( 97.5 % CI , -1.21 % to -0.53 % ) ( P<.001 vs baseline ) . The mean ( SD ) change in atheroma volume in the most diseased 10-mm subsegment was -6.1 ( 10.1 ) mm3 , with a median of -5.6 mm3 ( 97.5 % CI , -6.8 to -4.0 mm3 ) ( P<.001 vs baseline ) . Change in total atheroma volume showed a 6.8 % median reduction ; with a mean ( SD ) reduction of -14.7 ( 25.7 ) mm3 , with a median of -12.5 mm3 ( 95 % CI , -15.1 to -10.5 mm3 ) ( P<.001 vs baseline ) . Adverse events were infrequent and similar to other statin trials . CONCLUSIONS Very high-intensity statin therapy using rosuvastatin 40 mg/d achieved an average LDL-C of 60.8 mg/dL and increased HDL-C by 14.7 % , result ing in significant regression of atherosclerosis for all 3 prespecified IVUS measures of disease burden . Treatment to LDL-C levels below currently accepted guidelines , when accompanied by significant HDL-C increases , can regress atherosclerosis in coronary disease patients . Further studies are needed to determine the effect of the observed changes on clinical outcome . TRIAL REGISTRATION Clinical Trials.gov Identifier : NCT00240318 BACKGROUND Alirocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , has been shown to reduce low-density lipoprotein ( LDL ) cholesterol levels in patients who are receiving statin therapy . Larger and longer-term studies are needed to establish safety and efficacy . METHODS We conducted a r and omized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter ( 1.8 mmol per liter ) or more and were receiving treatment with statins at the maximum tolerated dose ( the highest dose associated with an acceptable side-effect profile ) , with or without other lipid-lowering therapy . Patients were r and omly assigned in a 2:1 ratio to receive alirocumab ( 150 mg ) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks . The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24 . RESULTS At week 24 , the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points ( P<0.001 ) ; the treatment effect remained consistent over a period of 78 weeks . The alirocumab group , as compared with the placebo group , had higher rates of injection-site reactions ( 5.9 % vs. 4.2 % ) , myalgia ( 5.4 % vs. 2.9 % ) , neurocognitive events ( 1.2 % vs. 0.5 % ) , and ophthalmologic events ( 2.9 % vs. 1.9 % ) . In a post hoc analysis , the rate of major adverse cardiovascular events ( death from coronary heart disease , nonfatal myocardial infa rct ion , fatal or nonfatal ischemic stroke , or unstable angina requiring hospitalization ) was lower with alirocumab than with placebo ( 1.7 % vs. 3.3 % ; hazard ratio , 0.52 ; 95 % confidence interval , 0.31 to 0.90 ; nominal P=0.02 ) . CONCLUSIONS Over a period of 78 weeks , alirocumab , when added to statin therapy at the maximum tolerated dose , significantly reduced LDL cholesterol levels . In a post hoc analysis , there was evidence of a reduction in the rate of cardiovascular events with alirocumab . ( Funded by Sanofi and Regeneron Pharmaceuticals ; ODYSSEY LONG TERM Clinical Trials.gov number , NCT01507831 . ) BACKGROUND Evolocumab , a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 ( PCSK9 ) , significantly reduced low-density lipoprotein ( LDL ) cholesterol levels in short-term studies . We conducted two extension studies to obtain longer-term data . METHODS In two open-label , r and omized trials , we enrolled 4465 patients who had completed 1 of 12 phase 2 or 3 studies ( " parent trials " ) of evolocumab . Regardless of study -group assignments in the parent trials , eligible patients were r and omly assigned in a 2:1 ratio to receive either evolocumab ( 140 mg every 2 weeks or 420 mg monthly ) plus st and ard therapy or st and ard therapy alone . Patients were followed for a median of 11.1 months with assessment of lipid levels , safety , and ( as a prespecified exploratory analysis ) adjudicated cardiovascular events including death , myocardial infa rct ion , unstable angina , coronary revascularization , stroke , transient ischemic attack , and heart failure . Data from the two trials were combined . RESULTS As compared with st and ard therapy alone , evolocumab reduced the level of LDL cholesterol by 61 % , from a median of 120 mg per deciliter to 48 mg per deciliter ( P<0.001 ) . Most adverse events occurred with similar frequency in the two groups , although neurocognitive events were reported more frequently in the evolocumab group . The risk of adverse events , including neurocognitive events , did not vary significantly according to the achieved level of LDL cholesterol . The rate of cardiovascular events at 1 year was reduced from 2.18 % in the st and ard-therapy group to 0.95 % in the evolocumab group ( hazard ratio in the evolocumab group , 0.47 ; 95 % confidence interval , 0.28 to 0.78 ; P=0.003 ) . CONCLUSIONS During approximately 1 year of therapy , the use of evolocumab plus st and ard therapy , as compared with st and ard therapy alone , significantly reduced LDL cholesterol levels and reduced the incidence of cardiovascular events in a prespecified but exploratory analysis . ( Funded by Amgen ; OSLER-1 and OSLER-2 Clinical Trials.gov numbers , NCT01439880 and NCT01854918 . ) BACKGROUND Statin-mediated low-density lipoprotein cholesterol ( LDL-C ) lowering fails to prevent more than half of cardiovascular events in clinical trials . Serial plaque imaging studies have highlighted the benefits of aggressive LDL-C lowering , with plaque regression evident in up to two-thirds of patients with achieved LDL-C levels < 70 mg/dL. Proprotein convertase subtilisin/kexin type 9 ( PCSK9 ) inhibitors permit LDL-C-lowering by a further 54 % to 75 % in statin-treated patients . The impact of achieving very low LDL-C levels with PCSK9 inhibitors on coronary atherosclerosis has not been investigated . AIMS To test the hypothesis that incremental LDL-C lowering with the PCSK9 inhibitor , evolocumab , will result in a significantly greater change from baseline in coronary atheroma volume than placebo in subjects receiving maximally tolerated statin therapy . METHODS A phase 3 , multicenter , double-blind , r and omized , placebo-controlled trial evaluating the impact of evolocumab on coronary atheroma volume as assessed by serial coronary intravascular ultrasound at baseline in patients undergoing a clinical ly indicated coronary angiogram with angiographic evidence of coronary atheroma , and after 78 weeks of treatment . Subjects ( n = 968 ) were r and omized 1:1 into 2 groups to receive monthly either evolocumab 420 mg or placebo subcutaneous injections . CONCLUSIONS The GLAGOV trial will explore whether greater degrees of plaque regression are achievable with ultrahigh-intensity LDL-C lowering after combination statin-PCSK9 inhibitor therapy . GLAGOV will provide important mechanistic , safety , and efficacy data prior to the eagerly anticipated clinical outcomes trials testing the PCSK9 inhibitor hypothesis ( www . clinical trials.gov identifier NCT01813422 ) Guidelines now recommend high-intensity statin therapy in all patients with proven atherosclerotic disease . Yet the impact of baseline lipoprotein and C-reactive protein ( CRP ) levels on measures of disease regression to this therapy are unknown . The aim of this study was to test the hypothesis that high-intensity statin therapy causes equivalent degrees of coronary atheroma regression irrespective of baseline lipoprotein and CRP levels . In 8 prospect i ve r and omized trials using serial coronary intravascular ultrasound , 1,881 patients who maintained or switched to 18- to 24 months of high-intensity statin therapy ( rosuvastatin 40 mg or atorvastatin 80 mg ) were stratified according to baseline lipoprotein and CRP levels . Changes in coronary percentage atheroma volume ( PAV ) and total atheroma volume ( TAV ) were evaluated . High-intensity statin therapy produced significant reductions from baseline in low-density lipoprotein cholesterol by 38.4 % , non-high-density lipoprotein ( HDL ) cholesterol by 33.6 % , triglycerides by 13.1 % , and CRP by 33.3 % , while increasing HDL cholesterol by 11.7 % ( p < 0.001 for all ) . This was associated with regression of PAV by 0.7 % and of TAV by 8.2 mm(3 ) ( p < 0.001 for both ) . No significant differences of changes in PAV and TAV were observed across baseline quintiles of low-density lipoprotein cholesterol , HDL cholesterol , non-HDL cholesterol , triglycerides , or CRP . Moreover , across all measured lipoproteins and CRP , most patients demonstrated plaque regression ( defined as any change from baseline in PAV or TAV < 0 ) . In conclusion , high-intensity statin therapy attenuated the natural progression of coronary atherosclerosis in all strata of patients with coronary artery disease irrespective of baseline lipoprotein or CRP levels . These findings provide support for the latest United States guideline recommendations for the broad use of high-intensity statin therapy in all patients with atherosclerosis , regardless of baseline lipid status Atherosclerotic cardiovascular disease ( ASCVD ) is the leading cause of death , decreased quality of life , and medical costs in the United States . Nearly 1 in 3 Americans die of heart disease and stroke ( 1 ) . Most ASCVD is preventable through a healthy lifestyle and effective treatment of cholesterol and blood pressure . The 2013 Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults from the American College of Cardiology and American Heart Association ( ACC/AHA ) provides an evidence -based approach to reducing ASCVD risk ( 2 ) . Guideline Development Process In 2008 , the National Heart , Lung , and Blood Institute ( NHLBI ) convened the Adult Treatment Panel ( ATP ) IV to up date the 2001 ATP-III cholesterol guidelines using a rigorous systematic process to identify and review r and omized , controlled trials ( RCTs ) with cardiovascular outcomes and meta-analyses of these RCTs . The panel comprised experts and clinicians from the fields of cardiology , epidemiology , primary care , and endocrinology ( 2 ) and received support from the Lifestyle Management and Risk Assessment Work Groups ( 3 , 4 ) . Systematic evidence review s conducted according to principles recommended by the Institute of Medicine ( 5 ) were performed to answer 3 questions relevant to clinical care . Two questions focused on the evidence supporting low-density lipoprotein cholesterol ( LDL-C ) and nonhigh-density lipoprotein cholesterol ( HDL-C ) levels as targets of treatment . One question examined the reduction in ASCVD events and adverse effects for each cholesterol-lowering drug class . The panel synthesized the evidence from these 3 review s as well as from Lifestyle Management and Risk Assessment Work Groups review s ( 3 , 4 ) that addressed 5 additional critical questions . Systematic electronic search es of relevant data bases of the peer- review ed English- language literature published from 1 January 1995 through 1 December 2009 for each critical question were conducted by an NHLBI-selected independent contractor and focused on RCTs and systematic review s and meta-analyses of RCTs assessed as fair to good quality . In addition , RCTs with ASCVD outcomes that included coronary heart disease , stroke , and cardiovascular deaths published after that date were eligible for consideration through July 2013 . Evidence tables were constructed , and the strength of evidence was rated according to the NHLBI ( Table 1 of the Supplement ) . Recommendations were grade d according to criteria from the NHLBI ( Table 2 of the Supplement ) and ACC/AHA ( Table 3 of the Supplement ) . Because of the inherent differences in grading systems and the clinical questions driving the recommendations , alignment between the NHLBI and ACC/AHA formats was imperfect . A complete description of the methods used and results of the evidence review are provided in the guideline ( 2 ) and the NHLBI evidence report ( www.nhlbi.nih.gov/ guidelines /cholesterol/ser/index.htm ) . Supplement . NHLBI and ACC/AHA Criteria for Rating Strength of Evidence To help clinicians estimate ASCVD risk , the risk assessment working group developed the Pooled Cohort Equations using data from 5 NHLBI-sponsored longitudinal , population -based cohorts of African American and non-Hispanic white men and women to estimate risk for a first myocardial infa rct ion , coronary heart disease death , or fatal or nonfatal stroke on the basis of age , sex , race , smoking status , total cholesterol level , HDL-C level , systolic blood pressure , antihypertensive therapy , and diabetes ( 4 , 6 ) . These equations significantly advance ASCVD risk estimation by providing sex- and race-specific estimates and including stroke as an outcome . The earlier Framingham equations calculated only coronary heart disease risk for non-Hispanic whites . The draft recommendations were review ed by 23 experts and representatives of federal agencies identified by the NHLBI . In September 2013 , the recommendations developed by the panel were transitioned to the ACC/AHA and had additional review by 4 experts nominated by the ACC Foundation and the AHA . The governing bodies of the ACC and AHA approved the guideline , which also received endorsement from the American Association of Cardiovascular and Pulmonary Rehabilitation , American Pharmacists Association , American Society for Preventive Cardiology , Association of Black Cardiologists , Preventive Cardiovascular Nurses Association , and WomenHeart : The National Coalition for Women with Heart Disease . Recommendations The guideline focuses on treatment of blood cholesterol to reduce ASCVD risk in adults . Major recommendations are summarized here and in Table 1 . The guideline report provides a complete listing of recommendations and supporting evidence behind each recommendation ( 2 ) . Table 1 . Major Recommendations for the Treatment of Blood Cholesterol to Reduce ASCVD Risk in Adults * 1 . Encourage Adherence to a Healthy Lifestyle A healthy lifestyle is the foundation for cardiovascular health . The panel endorsed the 2013 ACC/AHA Lifestyle Management Guideline ( 3 ) for a diet that is low in saturated fat , trans fat , and sodium ; emphasizes vegetables , fruits , whole grains , low-fat dairy products , poultry , fish , legumes , nontropical vegetable oils , and nuts ; and limits sweets , sugar-sweetened beverages , and red meats and engage in regular aerobic physical activity . Adults also should maintain a healthy body weight , avoid smoking , and control hypertension and diabetes when present . 2 . Statin Therapy Is Recommended for Adults in Groups Demonstrated to Benefit Strong RCT evidence shows that reduction in ASCVD events from statin therapy exceeds adverse events for 4 patient groups : those with clinical ASCVD ( acute coronary syndromes , myocardial infa rct ion , stable angina , coronary or other arterial revascularization , stroke , transient ischemic attack , or peripheral arterial disease of atherosclerotic origin ) when statins are used for secondary prevention , and those with LDL-C levels 190 mg/dL ; those aged 40 to 75 years with diabetes and LDL-C levels 70 to 189 mg/dL ; and those aged 40 to 75 years without diabetes and with a 10-year ASCVD risk 7.5 % when statins are used for primary prevention . Moderate evidence supports consideration of statin therapy for primary prevention in individuals with a 10-year ASCVD risk of 5 % to < 7.5 % . Routine initiation of statin therapy is not recommended in adults with New York Heart Association heart failure class II to IV or those receiving maintenance hemodialysis . R and omized , controlled trials in these groups showed no reduction in ASCVD . 3 . Statins have an Acceptable Margin of Safety When Used in Properly Selected Individuals and Appropriately Monitored Strong RCT evidence supports safety of statins when they are used as directed in conjunction with regular follow-up assessment s in properly selected patients . Adjustment of statin intensity is recommended in individuals older than 75 years with a history of statin intolerance or other characteristics ( 2 ) or those receiving drug therapy that may increase statin adverse events . Routine monitoring of hepatic aminotransferase level or creatine kinase level is not recommended unless clinical ly indicated by symptoms suggesting hepatotoxicity or myopathy . Given the potential for decreasing ASCVD events and death , the relationship of muscle and other symptoms to statin treatment must be confirmed . Therefore , eliciting a history of muscle symptoms before statin initiation and carefully monitoring symptoms during statin discontinuation and rechallenge is recommended . Severe myopathy , rhabdomyolysis , and possibly hemorrhagic stroke are rare complications of statin therapy . Although statin therapy modestly increases the risk for type 2 diabetes , ASCVD risk reduction outweighs the excess risk for diabetes for high-intensity statins in secondary prevention or for 10-year ASCVD risk 7.5 % . Similarly , ASCVD risk reduction outweighs the excess risk for diabetes for moderate-intensity statin therapy in adults with a 10-year ASCVD risk 5 % . 4 . Engage in a ClinicianPatient Discussion Before Initiating Statin Therapy , Especially for Primary Prevention in Patients With Lower ASCVD Risk Decisions to initiate statin therapy in primary prevention should be based on clinical judgment and preferences of informed patients . In adults without clinical ASCVD or diabetes whose LDL-C level is < 190 mg/dL , calculating the estimated 10-year ASCVD risk should be the start of the clinicianpatient discussion and should not automatically lead to statin initiation . As the absolute risk for ASCVD events decreases , so does the net benefit of the intervention . Therefore , discussion of the potential for ASCVD event reduction , adverse effects , drugdrug interactions , and patient preferences is especially important for lower-risk primary prevention . The discussion provides the opportunity to encourage healthy lifestyle habits and control other risk factors . Additional factors may be considered when a risk-based decision is uncertain , including LDL-C levels 160 mg/dL , family history of premature ASCVD , elevated lifetime ASCVD risk , high-sensitivity C-reactive protein level 2.0 mg/L , coronary artery calcification score > 300 Agatston units , and anklebrachial index < 0.9 . After age 75 years , comorbid conditions , anticipated longevity , safety considerations , and patient preferences should play a large role in decision making . 5 . Use the Newly Developed Pooled Cohort Equations for Estimating 10-Year ASCVD Risk The Pooled Cohort Equations are currently the best available method for estimating 10-year ASCVD risk to guide statin initiation ( 4 , 6 ) . Application of the inclusion and exclusion criteria from RCTs is cumbersome and results in underidentifying high-risk and overidentifying low-risk individuals for statin treatment . The Pooled Cohort Equations were developed using recent data from 5 NHLBI-sponsored , longitudinal , population -based cohorts of African American and white men and women ( ARIC [ |
12,892 | 29,535,067 | Robust effects emerged for feeding , cognitive and neurobehavioral development .
Wide differences emerged in infants ’ characteristics and maternal voice exposure methods .
Inconsistency emerged for physiological outcomes ( e.g. , heart rate variability , oxygen saturation , number of critical alarm events ) , whereas a robust pattern of findings emerged for feeding behaviors , as well as cognitive and neurobehavioral development .
Maternal voice appears to be a non‐noxious intervention , which is consistent with developmental care and which can be embedded in developmental care strategies | HIGHLIGHTSPreterm infants are precociously separated from the mother .
Maternal voice might facilitate mother‐infant contact during hospitalization .
Maternal voice exposure should be delivered to preterm infants and their mothers .
ABSTRACT Preterm infants are hospitalized in the Neonatal Intensive Care Unit ( NICU ) and are precociously separated from their mothers .
Although developmental care interventions are meant to facilitate mother‐infant bonding , physical contact is not always possible .
Maternal voice exposure has been proposed as a way to foster maternal closeness and support postnatal bonding .
Here we present a systematic review on maternal voice effects on preterm infants ’ development . | OBJECTIVE To test the efficacy of maternal skin-to-skin contact , or kangaroo care ( KC ) , on diminishing the pain response of preterm neonates to heel lancing . DESIGN A crossover design was used , in which the neonates served as their own controls . Subjects Preterm neonates ( n = 74 ) , between 32 and 36 weeks ' postmenstrual age and within 10 days of birth , who were breathing without assistance and who were not receiving sedatives or analgesics in 3 level II to III neonatal intensive care units in Canada . INTERVENTIONS In the experimental condition , the neonate was held in KC for 30 minutes before the heel-lancing procedure and remained in KC for the duration of the procedure . In the control condition , the neonate was in the prone position in the isolette . The ordering of conditions was r and om . MAIN OUTCOME MEASURES The primary outcome was the Premature Infant Pain Profile , which is composed of 3 facial actions , maximum heart rate , and minimum oxygen saturation changes from baseline in 30-second blocks . Videotapes , taken with the camera positioned on the neonate 's face so that an observer could not tell whether the neonate was being held or was in the isolette , were coded by research assistants who were naïve to the purpose of the study . Heart rate and oxygen levels were continuously monitored into a computer for later analysis . A repeated- measures analysis of covariance was used , with order of condition and site as factors and severity of illness as a covariate . RESULTS Premature Infant Pain Profile scores across the first 90 seconds from the heel-lancing procedure were significantly ( .002<P<.04 ) lower by 2 points in the KC condition . CONCLUSIONS For preterm neonates who are 32 weeks ' postmenstrual age or older , KC seems to effectively decrease pain from heel lancing . Further study is needed to determine if younger neonates or those requiring assistance in breathing , or older infants or toddlers , would benefit from KC , or if it would remain effective over several procedures . Given its effectiveness , and that parents of neonates in critical care units want to participate more in comforting their children , KC is a potentially beneficial strategy for promoting family health OBJECTIVE : To determine the sound environment of preterm infants cared for in the NICU and to test the hypothesis that infants exposed to more adult language will make more vocalizations . METHODS : This was a prospect i ve cohort study of 36 infants who had a birth weight of ≤1250 g. Sixteen-hour recordings of the infant sound environment were made in the NICU from a digital language processor at 32 and 36 weeks ' postmenstrual age . Adult word counts , infant vocalizations , and conversational turns were analyzed . RESULTS : Infant vocalizations are present as early as 32 weeks . Both adult word counts per hour and infant vocalizations per hour increase significantly between 32 and 36 weeks . Infant exposure to language as a percentage of time was small but increased significantly . When a parent was present , infants had significantly more conversational turns per hour than when a parent was not present at both 32 and 36 weeks ( P < .0001 ) . CONCLUSIONS : Preterm infants begin to make vocalizations at least 8 weeks before their projected due date and significantly increase their number of vocalizations over time . Although infant exposure to language increased over time , adult language accounted for only a small percentage of the sounds to which an infant is exposed in the NICU . Exposure to parental talk was a significantly stronger predictor of infant vocalizations at 32 weeks and conversational turns at 32 and 36 weeks than language from other adults . These findings highlight the powerful impact that parent talk has on the appearance and increment of vocalizations in preterm infants in the NICU To study the effects of live maternal speaking and singing on physiological parameters of preterm infants in the NICU and to test the hypothesis that vocal stimulation can have differential effects on preterm infants at a behavioural level OBJECTIVE : The goal of this study was to test the association of mean adult word counts at 32 and 36 weeks ’ postmenstrual age in the NICU with Bayley Scales of Infant and Toddler Development , 3rd Edition ( Bayley-III ) , cognitive and language scores . It was hypothesized that preterm infants exposed to higher word counts would have higher cognitive and language scores at 7 and 18 months ’ corrected age . METHODS : This prospect i ve cohort study included 36 preterm infants with a birth weight ≤1250 g. Sixteen-hour recordings were made in the NICU by using a digital language processor at 32 and 36 weeks ’ postmenstrual age . Regression analyses were performed on adult word count per hour , with Bayley-III measures correcting for birth weight . RESULTS : Adult word counts in the NICU were positively correlated with 7- and 18-month Bayley-III scores . For the 32-week recording , in regression analyses adjusting for birth weight , adult word count per hour independently accounted for 12 % of the variance in language composite scores ( P = .04 ) and 20 % of the variance in expressive communication scores at 18 months ( P = .008 ) . For the 36-week recording , adult word count per hour independently accounted for 26 % of the variance in cognitive composite scores at 7 months ( P = .0049 ) . CONCLUSIONS : Increased amount of parent talk with preterm infants in the NICU was associated with higher 7- and 18-month corrected age Bayley-III language and cognitive scores . These findings offer an opportunity for language intervention starting in the NICU PURPOSE To determine if a recording of a mother 's voice talking soothingly to her baby is useful in diminishing pain in newborns born between 32 and 36 weeks ' gestational age ( GA ) during routine painful procedures . BACKGROUND While maternal skin-to-skin contact has been proven efficacious for diminishing procedural pain in both full-term and preterm neonates , it is often not possible for mothers to be present during a painful procedure . Because auditory development occurs before the third trimester of gestation , it was hypothesized that maternal voice could substitute for maternal presence and be effective in diminishing pain response . SUBJECTSPreterm infants between 32 and 36 weeks ' GA ( n = 20 ) in the first 10 days of life admitted to 2 urban university-affiliated neonatal intensive care units . DESIGN AND METHODS Crossover design with r and om ordering of condition . Following informed consent , an audio recording of the mother talking soothingly to her baby was filtered to simulate the mother 's voice traveling through amniotic fluid . A final 10-minute recording of repetition of mothers ' talking was recorded with maximum peaks of 70 decibels ( dB ) and played at levels ranging between 60 and 70 ambient decibels ( dbA ) , selected above recommendations of the American Academy of Pediatrics in order to be heard over high ambient noise in the setting s. This was played to her infant by a portable cassette tape player 3 times daily during a 48-hour period after feedings ( gavage , bottle , or breast ) . At the end of 48 hours when blood work was required for clinical purpose s , using a crossover design , the infant underwent the heel lancing with or without the recording being played . The order of condition was r and omized , and the second condition was within 10 days . The Premature Infant Pain Profile ( PIPP ) was used as primary outcome . This is a composite measure using heart rate , oxygen saturation , 3 facial actions , behavioral state , and gestational age . This measure has demonstrated reliability and validity indexes . RESULTS There were no significant differences between groups on the PIPP or any of the individual components of the PIPP except a lower oxygen saturation level in the voice condition following the procedure . The second condition , regardless of whether it was voice or control , had higher heart rate scores and lower oxygen saturation scores even in the prelance baseline and warming phases . Order did not affect PIPP scores or facial actions . CONCLUSIONS Different modalities of maternal presence would appear to be necessary to blunt pain response in infants , and recorded maternal voice alone is not sufficient . The loudness of the recording may have obliterated the infant 's ability to discern the mother 's voice and may even have been aversive , reflected in decreased oxygen saturation levels in the voice condition . Preterm neonates of 32 to 36 weeks ' gestation may become sensitized to painful experiences and show anticipatory physiological response Aversive environment auditory stimuli is a common concern in neonatal intensive care . Recently , interest has developed regarding the use of music applications to mask such stimuli and to reduce the high risk for complications or failure to thrive . In this study of 20 oxygenated , low birth weight infants in a Newborn Intensive Care Unit of a regional medical center in the Southeastern United States , 10 infants listened to lullabies and 10 infants to recordings of their mother 's voice through earphones for 20 minutes across three consecutive days . Oxygen saturation levels and frequency of oximeter alarms were recorded . Results indicated a differential response to the two auditory stimuli as listening time progressed . On Day 1 , the infants listening to music had significantly higher oxygen saturation levels , but these effects disappeared by Days 2 and 3 . On Days 2 and 3 , however , the babies hearing music had significantly depressed oxygen saturation levels during the posttest intervals after the music was terminated . Infants hearing music had significantly fewer occurrences of Oximeter alarms during auditory stimuli than did those listening to the mothers ' voice . Implication s for the therapeutic use of auditory stimuli in the Newborn Intensive Care Unit are discussed BACKGROUND Preterm infants complete their development in Neonatal Intensive Care Unit being exposed to environmental stimuli that lead to the early maturation of the sensory systems . It is known that the fetus perceives sounds and reacts to them with movements since the 26th-28th week of gestational age . Maternal voice represents a source of sensory stimulation for the fetus . AIMS To investigate the effect of the exposure to maternal voice , administered by bone conduction , on preterm infants autonomic and neurobehavioral development . STUDY DESIGN Longitudinal , explorative , case control study . SUBJECTS 71 preterm infants with birth weight < 1500 g , born adequate for gestational age OUTCOME MEASURES vital and neurobehavioral parameters at term , neurofunctional assessment at 3 and 6months of corrected age . RESULTS Infants in the treatment group had lower heart rate values and a higher proportion of stable skin color at each study point as compared to the control group . The scores in the visual attention performance and in the quality of the general movements at term were better in the treatment group than in the control one . Neurofunctional assessment score at 3months of corrected age was higher in the treatment group whereas no difference between the two groups was detected at 6months of corrected age . CONCLUSIONS Early exposure to maternal voice exerts a beneficial effect on preterm infants autonomic and neurobehavioral development OBJECTIVES : We conducted a r and omized trial to test the hypothesis that mother ’s voice played through a pacifier-activated music player ( PAM ) during nonnutritive sucking would improve the development of sucking ability and promote more effective oral feeding in preterm infants . METHODS : Preterm infants between 34 0/7 and 35 6/7 weeks ’ postmenstrual age , including those with brain injury , who were taking at least half their feedings enterally and less than half orally , were r and omly assigned to receive 5 daily 15-minute sessions of either PAM with mother ’s recorded voice or no PAM , along with routine nonnutritive sucking and maternal care in both groups . Assignment was masked to the clinical team . RESULTS : Ninety-four infants ( 46 and 48 in the PAM intervention and control groups , respectively ) completed the study . The intervention group had significantly increased oral feeding rate ( 2.0 vs 0.9 mL/min , P < .001 ) , oral volume intake ( 91.1 vs 48.1 mL/kg/d , P = .001 ) , oral feeds/day ( 6.5 vs 4.0 , P < .001 ) , and faster time-to-full oral feedings ( 31 vs 38 d , P = .04 ) compared with controls . Weight gain and cortisol levels during the 5-day protocol were not different between groups . Average hospital stays were 20 % shorter in the PAM group , but the difference was not significant ( P = .07 ) . CONCLUSIONS : A PAM using mother ’s voice improves oral feeding skills in preterm infants without adverse effects on hormonal stress or growth Objective : To investigate the effects of parental presence and infant holding in the neonatal intensive care unit ( NICU ) on neurobehavior at term equivalent . Study Design : Prospect i ve cohort enrolled 81 infants born ⩽30 weeks gestation . Nurses tracked parent visitation , holding and skin-to-skin care throughout the NICU hospitalization . At term , the NICU Network Neurobehavioral Scale was administered . Associations between visitation , holding and early neurobehavior were determined using linear and logistic regression . Result : The mean hours per week of parent visitation was 21.33±20.88 ( median=13.90 ; interquartile range 10.10 to 23.60 ) . Infants were held an average of 2.29±1.47 days per week ( median=2.00 ; interquartile range 1.20 to 3.10 ) . Over the hospital stay , visitation hours decreased ( P=0.01 ) , while holding frequencies increased ( P<0.001 ) . More visitation was associated with better quality of movement ( P=0.02 ) , less arousal ( P=0.01 ) , less excitability ( P=0.03 ) , more lethargy ( P=0.01 ) and more hypotonia ( P<0.01 ) . More holding was associated with improved quality of movement ( P<0.01 ) , less stress ( P<0.01 ) , less arousal ( P=0.04 ) and less excitability ( P<0.01 ) . Conclusion : Infants of caregivers who were visited and held more often in the NICU had differences in early neurobehavior by term equivalent , which supports the need for and importance of early parenting in the NICU OBJECTIVE To examine the effects of biological maternal sounds ( BMS ) on weight gain velocity in very low-birth-weight ( VLBW ) infants ( ≤ 1,500 g ) . STUDY DESIGN An exploratory study with a matched-control design . A prospect i ve cohort of VLBW infants exposed to attenuated recordings of BMS during their neonatal intensive care unit hospitalization were compared with retrospective controls matched 1:1 for sex , birth weight , gestational age , scores for neonatal acute physiology and perinatal extension ( SNAPPE - II ) scores ( n = 32 ) . RESULTS A linear mixed model controlling for gestational age , chronic lung disease , and days to regain birth weight revealed that infants receiving BMS significantly improved their weight gain velocity compared matched controls ( p < 0.001 ) during the neonatal period . No differences were found on days spent nothing by mouth ( p = 0.18 ) , days until full enteral feeds ( p = 0.51 ) , total fluid intake ( p = 0.93 ) , or caloric intake ( p = 0.73 ) . CONCLUSION Exposure to BMS may improve weight gain velocity in VLBW infants . Further research is needed to evaluate the effectiveness of this noninvasive intervention during the neonatal period Objective : The effect of NIDCAP ( Newborn Individualized Developmental Care and Assessment Program ) was examined on the neurobehavioral , electrophysiological and neurostructural development of preterm infants with severe intrauterine growth restriction ( IUGR ) . Study Design : A total of 30 infants , 27–33 weeks gestation , were r and omized to control ( C ; N=17 ) or NIDCAP/experimental ( E ; N=13 ) care . Baseline health and demographics were assessed at intake ; electroencephalography ( EEG ) and magnetic resonance imaging ( MRI ) at 35 and 42 weeks postmenstrual age ; and health , growth and neurobehavior at 42 weeks and 9 months corrected age ( 9 months ) . Results : C and E infants were comparable in health and demographics at baseline . At follow-up , E infants were healthier , showed significantly improved brain development and better neurobehavior . Neurobehavior , EEG and MRI discriminated between C and E infants . Neurobehavior at 42 weeks correlated with EEG and MRI at 42 weeks and neurobehavior at 9 months . Conclusion : NIDCAP significantly improved IUGR preterm infants ' neurobehavior , electrophysiology and brain structure . Longer-term outcome assessment and larger sample s are recommended Significance Newborns can hear their mother ’s voice and heartbeat sounds before birth . However , it is unknown whether , how early , and to what extent the newborn 's brain is shaped by exposure to such maternal sounds . This study provides evidence for experience-dependent plasticity in the auditory cortex in preterm newborns exposed to authentic recordings of maternal sounds before full-term brain maturation . We demonstrate that the auditory cortex is more adaptive to womb-like maternal sounds than to environmental noise . Results are supported by the biological fact that maternal sounds would otherwise be present in utero had the baby not been born prematurely . We theorize that exposure to maternal sounds may provide newborns with the auditory fitness necessary to shape the brain for hearing and language development . Brain development is largely shaped by early sensory experience . However , it is currently unknown whether , how early , and to what extent the newborn ’s brain is shaped by exposure to maternal sounds when the brain is most sensitive to early life programming . The present study examined this question in 40 infants born extremely prematurely ( between 25- and 32-wk gestation ) in the first month of life . Newborns were r and omized to receive auditory enrichment in the form of audio recordings of maternal sounds ( including their mother ’s voice and heartbeat ) or routine exposure to hospital environmental noise . The groups were otherwise medically and demographically comparable . Cranial ultrasonography measurements were obtained at 30 ± 3 d of life . Results show that newborns exposed to maternal sounds had a significantly larger auditory cortex ( AC ) bilaterally compared with control newborns receiving st and ard care . The magnitude of the right and left AC thickness was significantly correlated with gestational age but not with the duration of sound exposure . Measurements of head circumference and the widths of the frontal horn ( FH ) and the corpus callosum ( CC ) were not significantly different between the two groups . This study provides evidence for experience-dependent plasticity in the primary AC before the brain has reached full-term maturation . Our results demonstrate that despite the immaturity of the auditory pathways , the AC is more adaptive to maternal sounds than environmental noise . Further studies are needed to better underst and the neural processes underlying this early brain plasticity and its functional implication s for future hearing and language development Objective : Preterm infants experience frequent cardiorespiratory events ( CREs ) including multiple episodes of apnea and bradycardia per day . This physiological instability is due to their immature autonomic nervous system and limited capacity for self-regulation . This study examined whether systematic exposure to maternal sounds can reduce the frequency of CREs in NICU infants . Methods : Fourteen preterm infants ( 26–32 weeks gestation ) served as their own controls as we measured the frequency of adverse CREs during exposure to either Maternal Sound Stimulation ( MSS ) or Routine Hospital Sounds ( RHS ) . MSS consisted of maternal voice and heartbeat sounds recorded individually for each infant . MSS was provided four times per 24-h period via a micro audio system installed in the infant ’s bed . Frequency of adverse CREs was determined based on monitor data and bedside documentation . Results : There was an overall decreasing trend in CREs with age . Lower frequency of CREs was observed during exposure to MSS versus RHS . This effect was significantly evident in infants ≥33 weeks gestation ( p = 0.03 ) , suggesting an effective therapeutic window for MSS when the infant ’s auditory brain development is most intact . Conclusion : This study provides preliminary evidence for short-term improvements in the physiological stability of NICU infants using MSS . Future studies are needed to investigate the potential of this non-pharmacological approach and its clinical relevance to the treatment of apnea of prematurity OBJECTIVE To describe and underst and how mothers utilize the opportunity to actively participate in their preterm infants ' pain care using facilitated tucking by parents ( FTP ) . DESIGN Descriptive and exploratory study with postintervention interview . SETTING Finnish level III Neonatal Intensive Care Unit ( NICU ) . PARTICIPANTS Twenty-three mothers who had preterm infants born at gestational ages of 32 to 34 weeks . METHODS The parents ( N=45 ) of 29 preterm infants were taught to use FTP . In addition , all nurses in the NICU ( N=76 ) received the same education to support the parents ' use of FTP . After 2 to 4 weeks of FTP use , the mothers ( n=23 ) were interviewed using the Clinical Interview for Parents of High-Risk Infants with additional questions related to the infants ' pain care . The interviews were analyzed inductively with cross-case analysis and deductively with a previously developed coding scheme . RESULTS Facilitated tucking by parents was perceived positively and was used by all participating mothers . Three different styles of involvement in preterm infants ' pain care with FTP were identified . They formed a continuum from external to r and om and finally to internalized involvement . In external involvement , the pain care with FTP was triggered by outside factors such as nurses , whereas in r and om and internalized involvement the motivation emerged from a parent . Mothers with external involvement thought that any person could apply the FTP . In r and om involvement , mothers were mainly absent during painful procedures , although they saw themselves as the best caregivers . In internalized involvement , the responsibility for infant pain care was shared within the family . Mothers ' NICU-related stress and maternal attachment were associated with this variation . CONCLUSION This study showed that mothers ' are willing to actively participate in their preterm infants ' pain care . However , the participation is unique according to mother and her experiences before and during NICU admission . Nurses need to consider these differences in mothers when involving them in preterm infants ' pain care The purpose of the study was to compare a heel stick conducted during Kangaroo Care ( skin-to-skin contact ) with the mother to a heel stick in a warmer in reducing premature infant physiologic and behavioral pain responses . Twenty-four premature infants in a university-based neonatal intensive care unit were recruited and r and omized to 2 sequences : sequence A group received 3 hours of Kangaroo Care ( with a heel stick in Kangaroo Care ) followed by 3 hours in a warmer ( with a heel stick in the warmer ) . Sequence B group had warmer care and a heel stick ( in the warmer ) before Kangaroo Care and a heel stick ( in Kangaroo Care ) . Heart rate , respiratory rate , oxygen saturation , crying time , and behavioral state were measured before , during , and after heel stick . Repeated measures ANOVA and Mann Whitney U statistics were performed . Heart rate and length of crying in response to pain were significantly reduced during Kangaroo Care and the Kangaroo Care heel stick as compared to when infants were in the warmer and had a heel stick in the warmer . Three infants did not cry at all during the Kangaroo Care heel stick ; infants slept more during Kangaroo Care than in the warmer . Kangaroo Care positioning before and during heel stick is a simple and inexpensive analgesic intervention to ameliorate pain in stable premature infants The purpose of this research was to determine the effects of mothers ' singing on their adjustment to and bonding with their new infants as well as use of music in the home environment in the first 2 weeks after their infants ' birth . Preterm mothers were assessed for coping with their infants ' NICU stay , and premature infants ' length of hospitalization was evaluated . Fifty-four full-term infants and mothers and 20 premature infants and 16 mothers were r and omly assigned to experimental or control conditions . Mothers in both experimental groups were recorded singing songs of their choice for use at home . Recordings of each preterm mother 's voice were played 20 minutes per day , 3 to 5 times per week , at a time when she was not able to visit her infant in the NICU . All full-term and preterm mothers in experimental and control groups completed a posttest survey 2 weeks after infants were discharged . Comparisons revealed that experimental preterm and full-term mothers indicated less adjustment to their baby and lifestyle changes and less bonding compared to control mothers , though this difference was not significant . Preterm and full-term experimental mothers reported the greatest number of postpartum medical complications , which might explain their poor adjustment and bonding scores . There was a significant difference between mothers ' value of music , with preterm experimental valuing music more . Preterm and full-term experimental mothers used music with and sang to infants more compared to preterm and full-term control mothers , but not to a significant degree . Preterm mothers reported a mean score of 4.75 ( with a 5 indicating that they strongly agreed ) for the following item : knowing my infant listened to my singing helped me to cope with my infant 's stay in the NICU . Furthermore , preterm infants who listened to the CD recording of their mothers ' singing left the hospital an average of 2 days sooner than those in the control group , though this difference was not significant The current study explores the effects of exposure to maternal voice on infant sucking in preterm infants . Twenty-four preterm infants averaging 35 weeks gestational age were divided r and omly into two groups . A contingency between high-amplitude sucking and presentation of maternal voice was instituted for one group while the other group served as a yoked control . No significant differences were observed in sucking of the two groups , but the degree of pitch modulation of the maternal voice predicted an increase in the rate of infant sucking |
12,893 | 27,262,840 | Similar differences were observed for physical HRQoL in further analyses accounting for possible confounding effects of age .
Osteoporotic older people with vertebral fracture have worse physical HRQoL than osteoporotic older people without vertebral fracture , even after accounting for age differences | Health-related quality of life in osteoporotic patients with vertebral fracture is of increasing interest , but relevant studies have yielded debatable results .
This systematic review and meta- analysis of 16 observational studies demonstrate a clear association between physical health status and presence of vertebral fracture after accounting for age .
This meta- analysis was conducted to identify if there are any differences between physical and /or mental health-related quality of life ( HRQoL ) in older people with osteoporosis based on conventional T-score definitions and the presence or absence of vertebral fracture . | Health-related quality of life ( HRQOL ; “ QOL ” hereafter ) was evaluated in Japanese osteoporotic patients using three question naires ; the SF-36 ( MOS 36-Item Short-Form Health Survey ; generic , profile-type ) , the EQ-5D ( Euro Qol-5 Dimensions ; generic , preference-based ) , and the JOQOL ( Japanese Osteoporosis Quality of Life 1999 ; disease-targeted ) . The eight subscales and two summary scores of the SF-36 were impaired in these patients even after correction for age and sex . The scores on the EQ-5D and JOQOL correlated well with the subscales of the SF-36 that represent the physical aspects of physical function and bodily pain , which suggests that physical aspects are important determinants of overall QOL status in osteoporotic patients . Although the QOL scores did not correlate with bone mineral density , they were markedly influenced by the presence of vertebral fractures . In particular , the presence of two or more vertebral fractures greatly decreased the QOL scores . We then evaluated the QOL scores before and after treatment . The patients were either given calcium supplementation alone or calcium plus once-weekly elcatonin ( Elcitonin , Asahi Kasei Pharma , Tokyo , Japan ) injection . Elcatonin treatment markedly improved diverse aspects of the QOL , whereas calcium alone did not . The current data suggest that osteoporosis , especially in the presence of vertebral fracture , is associated with compromised QOL , and therapeutic intervention for osteoporosis should be evaluated in terms of QOL , as well as in terms of increases in bone mineral density and fracture prevention Fractures and subsequent morbidity determine the impact of established postmenopausal osteoporosis . Health-related quality of life ( HRQOL ) has become an important outcome criterion in the assessment and follow-up of osteoporotic patients . As part of the baseline measurements of the Multiple Outcomes of Raloxifene Evaluation ( MORE ) study , HRQOL was assessed in 751 osteoporotic ( bone mineral density [ BMD ] T score > or = -2.5 ) women from Europe with or without vertebral fractures ( VFX ) . This was done using the quality of life question naire of the European Foundation for Osteoporosis ( QUALEFFO ) , Nottingham Health Profile ( NHP ) and the EQ-5D ( former EuroQol ) . QUALEFFO contains questions in five domains : pain , physical function , social function , general health perception , and mental function . Each domain score and QUALEFFO total scores are expressed on a 100-point scale , with 0 corresponding to the best HRQOL . In comparison with patients without VFX , those with VFX were older ( 66.2 + /- 5.9 years vs. 68.8 + /- 6.3 years ; p < 0.001 ) , had higher prevalence of nonvertebral fractures ( 25 % vs. 36 % ; p = 0.002 ) , and higher QUALEFFO scores ( worse HRQOL ; total score , 26 + /- 14 vs. 36 + /- 17 ; p < 0.001 ) . QUALEFFO scores increased progressively with increasing number of VFX , especially lumbar fractures ( p < 0.001 ) . Patients with a single VFX already had a significant increase in QUALEFFO scores ( p < 0.05 ) . Similar , though weaker , associations were seen for NHP and EQ-5D scores . This study confirms decreased HRQOL for patients with prevalent VFX . In osteoporotic patients , QUALEFFO scores change in relation to the number of VFX . QUALEFFO is suitable for clinical studies in patients with postmenopausal osteoporosis OBJECTIVE Vertebral fractures are a common complication of osteoporosis and may have a negative effect on health-related quality of life ( HRQOL ) . We investigated the effect of prevalent vertebral fractures on HRQOL in patients with osteoporosis . METHODS A cross-sectional multicenter study was carried out among postmenopausal women with primary osteoporosis attending primary care centers and hospital outpatient clinics : 234 women with vertebral fractures and 244 asymptomatic women . Women with secondary osteoporosis or taking medications that affect bone metabolism were excluded . All patients were question ed using the mini-Osteoporosis Quality of Life Question naire ( mini-OQLQ ) , Medical Outcomes Study Short Form-36 ( SF-36 ) , and the EuroQuol-5D , after assessment of all clinical variables and anthropometric data . To assess comorbidity we used the Self-Administered Comorbidity Question naire ( SCQ ) . Diagnosis of osteoporosis was confirmed in all patients by bone mineral density using dual energy x-ray absorptiometry . Radiographic evaluation was performed by a musculoskeletal radiologist . A total of 483 postmenopausal women , r and omly matched for age out of 1579 healthy controls , were chosen to compare the SF-36 scores with respect to patients with and without vertebral fractures due to osteoporosis . A multivariable regression analysis was conducted to identify the strongest determinant for low HRQOL , adjusted for potential confounding variables such as comorbid conditions , education level , and psychosocial status . RESULTS The vertebral fracture group had significantly lower scores than patients without fractures and controls in all domains of the generic and specific question naires . Women with only 1 prevalent fracture had statistically significantly lower HRQOL scores than those without fractures on SF-36 measures of bodily pain , physical functioning , and role function physical ( all p < 0.01 ) . HRQOL scores were lower in women with lumbar fractures compared with women with thoracic fractures only when the physical functioning and bodily pain dimensions approached statistical significance . Based on the multivariate analysis , the strongest determinant for low HRQOL was physical functioning ( explained by number of vertebral fractures ) followed by comorbidity score and age . Adjusted R2 in the final model was 35.9 % . Using the SF-36 summary scales , comorbid conditions predominantly affected either mental or physical health ( p < 0.0001 ) . A significant correlation ( p < 0.0001 ) was found between total score on the mini-OQLQ and the mean SCQ comorbidity score . CONCLUSION Our results confirm previous findings that HRQOL , assessed by generic and osteoporosis-specific instruments , is decreased in patients with vertebral fractures due to osteoporosis as a function of the number of vertebral fractures , presence of comorbid conditions , and age |
12,894 | 24,603,619 | However , no significant association was found between hyperopia or myopia and early AMD incidence .
Furthermore , neither prevalent nor incident late AMD was associated with refractive error .
Geographic location might play a role ; the heterogeneity became non-significant after stratifying these studies into Asian and non-Asian subgroups .
Refractive error is associated with early AMD but not with late AMD . | OBJECTIVE To summarize relevant evidence investigating the associations between refractive error and age-related macular degeneration ( AMD ) . | PURPOSE To study the relationship between baseline spherical equivalents ( SphE ) of refraction and prevalent as well as incident age-related maculopathy ( pARM and iARM , respectively ) . METHODS The study was performed as part of the Rotterdam Study , a population -based , prospect i ve cohort study . The SphE ( in diopters ) , measured with autorefraction and subjective optimization , was recorded in 6209 subjects aged 55 years or more . Aphakic or pseudophakic eyes at baseline were excluded . Stereoscopic transparencies of the macular region were grade d according to the International Classification and Grading System . ARM was defined as large soft drusen with pigmentary changes , or indistinct drusen , or atrophic or neovascular age-related macular degeneration ( AMD ) . For the prevalence analyses , ARM was classified into no , p(early)ARM , or pAMD , and in each subject the eye with the most advanced ARM and the corresponding refraction was selected . After a mean 5.2 years of follow-up , 4935 subjects had complete data for these incidence analyses . In each subject , the eye with iARM was selected . RESULTS The age- and gender-adjusted odds ratio ( OR ) of pARM ( n = 536 ) for every diopter of progress toward hyperopia was 1.09 ( 95 % confidence interval [CI]1.04 - 1.13 ) . For p(early)ARM ( n = 440 ) the OR was 1.09 ( 1.04 - 1.14 ) and for pAMD ( n = 96 ) the OR was 1.09 ( 1.00 - 1.19 ) . Baseline refraction was significantly associated with increased risk of iARM ( n = 497 ) . For each diopter of progress toward hyperopia the OR was 1.05 ( 95 % CI 1.01 - 1.10 ) . Additional adjustments for smoking , atherosclerosis , and blood pressure did not alter the relationship . CONCLUSIONS These population -based incidence data confirm results from prevalence and case-control studies that there is an association between hyperopia and ARM OBJECTIVE To describe the risk factors and associated population attributable risk for age-related maculopathy ( ARM ) and age-related macular degeneration ( AMD ) in Australians aged 40 years and older . METHODS Residents were recruited from 9 r and omly selected urban clusters and 4 r and omly selected rural clusters in Victoria , Australia . At locally established test sites , the following information was collected : visual acuity , medical and health history , lifetime sunlight exposure , dietary intake , and fundus photographs . Age-related maculopathy and AMD were grade d from the fundus photographs using an international classification and grading system . Backwards logistic regression was used to identify the independent risk factors for ARM and AMD . RESULTS The participation rate was 83 % ( n = 3271 ) among the urban residents and 92 % ( n = 1473 ) among the rural residents . Gradable fundus photographs of either eye were available for 4345 ( 92 % ) of the 4744 participants . There were 656 cases of ARM , giving a weighted prevalence of 15.1 % ( 95 % confidence limit [ CL ] , 13.8 , 16.4 ) ; and there were 30 cases of AMD , giving a weighted prevalence of 0.69 % ( 95 % CL , 0.33 , 1.03 ) . In multiple logistic regression , the risk factors for AMD were as follows : age ( odds ratio [ OR ] , 1.23 ; 95 % CL , 1.17 , 1.29 ) , smoked cigarettes for longer than 40 years ( OR , 2.39 ; 95 % CL , 1.02 , 5.57 ) , and ever taken angiotensin-converting enzyme inhibitors ( OR , 3.26 ; 95 % CL , 1.33 , 8.01 ) . The magnitude of all of these risk factors was slightly less for ARM , and having ever taken blood cholesterol-lowering medications was also significant ( OR , 1.67 ; 95 % CL , 1.12 , 2.47 ; P = .001 ) . CONCLUSION Smoking is the only modifiable risk factor for ARM and AMD , among the many environmental and systemic factors that were assessed PURPOSE To assess the prevalence and associated risk factors of age-related macular degeneration ( AMD ) in an elderly Chinese population in Taiwan . METHODS The Shihpai Eye Study was a survey of vision and ocular disease in an elderly Chinese population 65 years of age or older residing in Shihpai , Taipei , Taiwan . Of 2045 elderly residents r and omly sample d from the household registration data bank , 1361 ( 66.6 % ) underwent a detailed ophthalmic examination that included fundus color slides by fundus camera after pupil dilatation . Photographs were grade d according to the Wisconsin Age-Related Maculopathy Grading System . RESULTS Fundus photographs were available for 1105 ( 54.0 % in the eligible , 81.2 % in the ocular examined ) participants . The 47 ( 4.3 % ) participants who had ungradable fundus images were older and had more lens opacity . Of the 1058 gradable photographs , the prevalence of early AMD was 9.2 % ( 95 % confidence interval [ CI ] , 7.8 - 10.8 ) ; of late AMD , 1.9 % ( 95 % CI , 1.3 - 2.7 ) ; of soft drusen , 42.2 % ( 95 % CI , 39.7 - 44.8 ) ; of soft indistinct drusen , 4.1 % ( 95 % CI , 3.1 - 5.2 ) ; and of any pigmentary change , 8.6 % ( 95 % CI , 7.2 - 10.2 ) . Age was the most significant factor associated with both early and late AMD . The prevalence of early AMD rose from 5.0 % in the 65- to 69-year age group to 24.4 % in those 80 years of age and older ; and for late AMD , from 1.0 % to 9.0 % . Those who currently drank alcohol had a lower rate of early AMD than did the nondrinker ( adjusted odd ratio 0.32 , 95 % CI : 0.11 - 0.93 , P = 0.037 ) . CONCLUSIONS AMD is a common eye disease in the elderly Chinese people in Taiwan . The adjusted prevalence rate of exudative AMD is comparable to that in the Chinese people in the Multiethnic Study of Atherosclerosis ( MESA ) in the United States but is higher than in the Chinese people in the Beijing study in China . Further studies are needed to clarify the incidence and associated risk factors OBJECTIVE To investigate possible risk factors for age-related macular degeneration ( AMD ) in participants in the Age-Related Eye Disease Study ( AREDS ) . DESIGN Case-control study . PARTICIPANTS Of the 4757 persons enrolled in AREDS , 4519 persons aged 60 to 80 years were included in this study . The lesions associated with AMD ranged from absent in both eyes to advanced in one eye . MAIN OUTCOME MEASURES Stereoscopic color fundus photographs of the macula were used to place participants into one of five groups , based on the frequency and severity of lesions associated with AMD . Participants with fewer than 15 small drusen served as the control group . RESULTS Staged model building techniques were used to compare each of the four case groups with the control group . Increased age was a consistent finding of all four of the case groups compared with the control group , and all the following associations were age adjusted . Persons with either intermediate drusen , extensive small drusen , or the pigment abnormalities associated with AMD ( group 2 ) were more likely to be female , more likely to have a history of arthritis , and less likely to have a history of angina . Persons with one or more large drusen or extensive intermediate drusen ( group 3 ) were more likely to use hydrochlorothiazide diuretics and more likely to have arthritis . Hypertension , hyperopia , presence of lens opacities , and white race were also found more frequently in this group as well as in persons with neovascular AMD ( group 5 ) . Only persons in group 5 were more likely to have an increased body mass index , whereas persons with geographic atrophy ( group 4 ) as well as those in groups 3 and 5 were more likely to have completed fewer years in school or to be smokers . Those with geographic atrophy were also more likely to use thyroid hormones and antacids . CONCLUSIONS Our findings for smoking and hypertension , which have been noted in previous studies , suggest that two important public health recommendations , the avoidance of smoking and the prevention of hypertension , may reduce the risk of developing AMD . Other associations , such as those for hyperopia , lens opacities , less education , female gender , increased body mass index , and white race , which have been noted in other studies , are also seen in the AREDS population . The increased use of thyroid hormones and antacids in persons with geographic atrophy and the increased likelihood of arthritis or hydrochlorothiazide use in persons with one or more large drusen or extensive intermediate drusen have not been previously reported and need additional investigation PURPOSE To compare the ocular rigidity in vivo measurements of patients with age-related macular degeneration ( AMD ) and control subjects . DESIGN Prospect i ve comparative clinical study . METHODS The pressure-volume relation and the ocular rigidity coefficient were compared among 32 patients with AMD ( AMD group : 16 with neovascular and 16 with nonneovascular AMD ) and 44 age-matched control patients ( control group ) who underwent operation for cataract . This was achieved by an injection of 200 microl of a balanced salt solution ( in steps of 4.5 microl ) through the limbus in the anterior chamber , while the intraocular pressure was monitored continually with a transducer , up to the limit of 30 mm Hg . RESULTS The mean age ( AMD group : 69.89 + /- 15.92 years vs control group : 65.28 + /- 12.34 years ; P = .195 ) , gender ( AMD group : 13 female vs control group : 17 female ; P = .513 ) , eye 's axial length ( AMD group : 23.14 + /- 0.75 mm vs control group : 23.04 + /- 1.16 mm ; P = .725 ) of patients with AMD and the healthy control subjects were comparable . No statistically significant difference in ocular rigidity measurements between patients with AMD and control subjects ( AMD group : 0.0142 + /- 0.0077 microl(-1 ) vs control group : 0.0125 + /- 0.0049 microl(-1 ) ; P = .255 ) was found . When we examined separately the two subgroups of patients with AMD ( neovascular and nonneovascular AMD ) , the average ocular rigidity measurements were higher in patients with neovascular AMD vs both control subjects and patients with nonneovascular AMD ( neovascular AMD group : 0.0186 + /- 0.0078 microl(-1 ) vs control group : 0.0125 + /- 0.0048 microl(-1 ) [ P = .014 ] vs nonneovascular AMD group : 0.0104 + /- 0.0053 microl(-1 ) [ P = .004 ] ) . CONCLUSIONS Despite the limitations placed by the small sample of the examined cases , patients with neovascular AMD who are treated ( with photodynamic therapy ) have increased ocular rigidity measurements compared with patients with nonneovascular AMD and control patients OBJECTIVE To describe the prevalence of age-related macular degeneration ( AMD ) in 4 racial/ethnic groups ( white , black , Hispanic , and Chinese ) that participated in the second examination of the Multi-ethnic Study of Atherosclerosis ( MESA ) . DESIGN Prospect i ve cohort study . PARTICIPANTS Six thous and one hundred seventy-six 45- to 85-year-old subjects selected from 6 United States communities . METHODS Fundus images were taken using a 45 degrees digital camera through dark-adapted pupils and were grade d for drusen size , type , area , increased retinal pigment , retinal pigment epithelial depigmentation , neovascular lesions , and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System . MAIN OUTCOME MEASURE Age-related macular degeneration . RESULTS Prevalences of AMD were 2.4 % ( black ) , 4.2 % ( Hispanic ) , 4.6 % ( Chinese ) , to 5.4 % ( white ) ( P<0.001 for any differences among groups ) . The highest prevalence of any AMD occurred in those 75 to 84 years old , varying from 7.4 % in blacks to 15.8 % in whites and Chinese ( P = 0.03 ) . Estimated prevalences of late AMD were 0.3 % ( black ) , 0.2 % ( Hispanic ) , 0.6 % ( white ) , and 1.0 % ( Chinese ) . These differences were marginally significant ( age and gender adjusted , P = 0.08 ) . The frequency of exudative AMD was highest in Chinese ( age- and gender-adjusted odds ratio , 4.30 ; 95 % confidence interval , 1.30 - 14.27 ) compared with whites . Differences in age , gender , pupil size , body mass index , smoking , alcohol drinking history , diabetes , and hypertension status did not explain the variability among the 4 racial/ethnic groups . CONCLUSIONS Low prevalences of AMD were found in the MESA cohort in all groups . A lower prevalence of AMD was found in blacks compared with whites . The higher prevalence of exudative AMD in Chinese needs further study PURPOSE To study the relationship between age-related maculopathy (ARM)/age-related macular degeneration ( AMD ) and phakic refraction and between ARM/AMD and axial length . METHODS The study was a point prevalence study that included 663 r and omly selected persons aged over 65 years . We measured axial length and refraction . Fundus images were grade d for ARM according to a modified Wisconsin Age-related Maculopathy Grading System st and ard . Data from both eyes were available from most participants . We analysed the results for both individual eyes and pairs . RESULTS The mean axial length was 23.22 mm for right eyes and 23.21 mm for left eyes . Women had a 0.57-mm shorter mean axial length than men . The mean refraction was + 1.0 dioptres ( D ) for right eyes and + 0.9 D for left eyes . At 70 years of age women were more hypermetropic than men by 0.66 D. There was no significant difference in refraction or axial length among the groups with different ARM stages . CONCLUSION We found no statistically significant relationship between axial length/refraction and AMD/ARM . There was a statistically significant sex difference in axial length and refraction , where women had shorter axial lengths and were more hypermetropic than men PURPOSE To describe the relationship of refractive errors to the 10-year incidence of age-related maculopathy ( ARM ) in a defined white population . METHODS Persons aged 43 to 86 years of age in Beaver Dam , Wisconsin , were invited for a baseline examination from 1988 through 1990 , and follow-up examinations 5 and 10 years later ( n = 3684 ) . Refraction was measured at baseline , with myopia defined as a spherical equivalent of -1.00 D or less , emmetropia as -0.75 to + 0.75 D and hyperopia as + 1.00 D or more . At each examination , signs of ARM were ascertained from grading stereoscopic color fundus photographs based on a st and ard protocol . The association between baseline refractive status and the 10-year incidence and progression of ARM was analyzed . RESULTS The 10-year cumulative incidence for early ARM was 7.1 % , 7.7 % , and 11.7 % , in eyes with myopia , emmetropia , and hyperopia , respectively . The corresponding 10-year cumulative incidence for late ARM was 0.3 % , 0.8 % , and 2.2 % . When age was controlled for , there was no association between myopia and incident early ( relative risk [ RR ] 1.0 , 95 % confidence interval [ CI ] , 0.7 - 1.3 ) and late ( RR 0.5 , 95 % CI , 0.2 - 1.5 ) ARM . Similarly , after controlling for age , hyperopia was not associated with incident early ( RR 0.9 , 95 % CI , 0.7 - 1.1 ) or late ( RR 1.2 , 95 % CI , 0.6 - 2.3 ) ARM . CONCLUSIONS These prospect i ve population -based data provide no evidence of an association between refractive errors and risk of ARM |
12,895 | 28,263,002 | It is concluded that supplementing dietary arginine in gestating sows can benefit embryo survival and foetal development . | The use of functional amino acids during pregnancy has been linked to improved reproduction in mammals .
In this context , arginine is a precursor in the synthesis of numerous molecules , such as nitric oxide and polyamines , which play an important role during reproduction .
However , contradictory studies are found in the literature , particularly regarding the amount of supplementation and the period of pregnancy in which it is used .
The objective of this study was to evaluate the effects of dietary arginine supplementation for pregnant sows on foetal development via a systematic review . | Arginine is a common substrate for the synthesis of nitric oxide and polyamines that are crucial for placental angiogenesis and growth in mammals . This study was conducted to test the hypothesis that dietary l-arginine supplementation may improve reproductive performance of pregnant gilts . Fifty-two pregnant gilts with body weight ( BW ) of 166.3 + /- 1.8 kg were housed individually in gestation crates . At d 30 of gestation , gilts were assigned r and omly to corn-soybean-based diets supplemented with 1.0 % L-arginine-HCl or 1.7 % L-alanine ( isonitrogenous control ) . Both diets contained 13.0 MJ metabolizable energy/kg and 12.2 % crude protein and were fed to gilts at 1 kg twice daily during gestation . Backfat thickness and BW were measured and blood sample s were obtained on 30 , 70 , 90 , and 110 d of gestation . At d 110 of gestation , gilts were transferred to individual farrowing crates . The numbers of total piglets born and born alive , as well as birth weights of piglets , were recorded immediately after farrowing . Throughout the gestation , BW or backfat thickness of gilts did not differ between treatment groups . Plasma urea concentrations were lower in arginine-supplemented than in control gilts at d 90 ( P < 0.010 ) and d 110 ( P < 0.001 ) of gestation . Compared with the control group , arginine supplementation increased the number of pigs born alive by 22 % ( 11.40 vs. 9.37 , P = 0.032 ) and live litter birth weight of piglets by 24 % ( 16.38 vs. 13.19 kg , P = 0.016 ) . This exciting finding provides the first evidence for a marked increase of live-born piglets by 2 per litter through nutritional intervention in gilts The effects of l-arginine on porcine foetal development and myogenesis were determined . Twenty Swiss Large White gilts were r and omly allocated to either the control ( C ) or l-arginine treatment ( A ) . In addition to the st and ard gestation diet , A-sows received 26 g l-arginine daily from days 14 to 28 of gestation . At day 75 of pregnancy , sows were sacrificed and the number and weight of foetuses were recorded . From each litter , the lightest , heaviest and the ones with an average foetal weight ( FtW ) were selected . Primary ( P ) , secondary ( S ) and total myofiber number as well as S/P ratio were determined in the semitendinosus ( ST ) and rhomboideus ( RH ) muscles . In A-sows , the number of viable foetuses ( 13.0 v. 9.3 ) and total FtW ( 4925 v. 3729 g ) was greater ( P ⩽ 0.04 ) than in C-sows . Compared to C-sow foetuses , the ST of A-sow foetuses had 7 % more ( 17 699 v. 16 477 ; P = 0.04 ) P myofibers and the S/P ratio in both muscles was lower ( ST = 20.3 v. 21.5 ; RH = 24.1 v. 27.1 ; P ⩽ 0.07 ) . Regardless of the maternal diet , the S myofiber number and the S/P ratio in both muscles were greater ( P ⩽ 0.01 ) in foetuses with a high FtW compared to low FtW. These data suggest that l-arginine supplemented to gilts during early gestation enhanced foetal survival and in the ST positively affected the primary phase of myofiber formation Placental vascular formation and blood flow are crucial for fetal survival , growth and development , and arginine regulates vascular development and function . This study determined the effects of dietary arginine or N-carbamylglutamate ( NCG ) supplementation during late gestation of sows on the microRNAs , vascular endothelial growth factor A ( VEGFA ) and endothelial nitric oxide synthase ( eNOS ) expression in umbilical vein . Twenty-seven l and race × large white sows at day ( d ) 90 of gestation were assigned r and omly to three groups and fed the following diets : a control diet and the control diet supplemented with 1.0 % l-arginine or 0.10 % NCG . Umbilical vein of fetuses with body weight around 2.0 kg ( oversized ) , 1.5 kg ( normal ) and 0.6 kg ( intrauterine growth restriction , IUGR ) were obtained immediately after farrowing for miR-15b , miR-16 , miR-221 , miR-222 , VEGFA and eNOS real-time PCR analysis . Compared with the control diets , dietary Arg or NCG supplementation enhanced the reproductive performance of sows , significantly increased ( P < 0.05 ) plasma arginine and decreased plasma VEGF and eNOS ( P < 0.05 ) . The miR-15b expression in the umbilical vein was higher ( P < 0.05 ) in the NCG-supplemented group than in the control group . There was a trend in that the miR-222 expression in the umbilical vein of the oversized fetuses was higher ( 0.05 < P < 0.1 ) than in the normal and IUGR fetuses . The expression of eNOS in both Arg-supplemented and NCG-supplemented group were lower ( P < 0.05 ) than in the control group . The expression of VEGFA was higher ( P < 0.05 ) in the NCG-supplemented group than in the Arg-supplemented and the control group . Meanwhile , the expression of VEGFA of the oversized fetuses was higher ( P < 0.05 ) than the normal and IUGR fetuses . In conclusion , this study demonstrated that dietary Arg or NCG supplementation may affect microRNAs ( miR-15b , miR-222 ) targeting VEGFA and eNOS gene expressions in umbilical vein , so as to regulate the function and volume of the umbilical vein , provide more nutrients and oxygen from the maternal to the fetus tissue for fetal development and survival , and enhance the reproductive performance of sows Suboptimal embryonic/fetal survival and growth remains a significant problem in mammals . Using a swine model , we tested the hypothesis that dietary l-arginine supplementation during gestation may improve pregnancy outcomes through enhancing placental growth and modulating hormonal secretions . Gestating pigs ( Yorkshire × L and race , n = 108 ) were assigned r and omly into two groups based on parity and body weight , representing dietary supplementation with 1.0 % l-arginine – HCl or 1.7 % l-alanine ( isonitrogenous control ) between days 22 and 114 of gestation . Blood sample s were obtained from the ear vein on days 22 , 40 , 70 and 90 of gestation . On days 40 , 70 and 90 of gestation , concentrations of estradiol in plasma were higher ( P < 0.05 ) in arginine-supplemented than in control sows . Moreover , arginine supplementation increased ( P < 0.05 ) the concentrations of arginine , proline and ornithine in plasma , but concentrations of urea or progesterone in plasma did not differ between the two groups of sows . Compared with the control , arginine supplementation increased ( P < 0.05 ) the total number of piglets by 1.31 per litter , the number of live-born piglets by 1.10 per litter , the litter birth weight for all piglets by 1.36 kg , and the litter birth weight for live-born piglets by 1.70 kg . Furthermore , arginine supplementation enhanced ( P < 0.05 ) placental weight by 16.2 % . The weaning-to-estrus interval of sows was not affected by arginine supplementation during gestation . These results indicate that dietary arginine supplementation beneficially enhances placental growth and the reproductive performance of sows The present study characterised gene expression associated with embryonic muscle development and placental vascularisation during early gestation in the pig and examined effects of Progenos supplementation in early pregnancy . Tissues were collected from commercial multiparous sows ( n = 48 ) from Days 16 to 49 of gestation . In the placenta , qPCR revealed that vascular endothelial growth factor ( VEGFA ) expression did not change from Day 17 to 49 of gestation ; however , KDR receptor and angiopoietin-1 and -2 expression were differentially regulated , with periods of high expression corresponding to two critical phases of angiogenesis in the pig . In the embryo , the pattern of myogenesis-related gene expression was consistent with available literature . A commercially available nutritional supplement Progenos ( 20 g day⁻¹ L-arginine ) added to the diet of sows from either Day 15 to 29 ( P15 - 29 ; n = 33 ) , Day 30 to 44 ( n = 29 ) or from Day 15 to 44 ( n = 76 ) of gestation tended to increase ( P = 0.058 ) embryonic growth rate compared with non-supplemented controls ( n = 79 ) and angiogenin expression was higher ( P = 0.028 ) at Day 30 of gestation in placentae from sows on the P15 - 29 Progenos treatment . These results are consistent with proposed beneficial effects of l-arginine on early embryonic development and placental vascularisation A 2 x 2 factorial arrangement of treatments in a r and omized block design was used to determine the effects of dietary Arg supplementation during gestation and lactation on the lactation performance of 38 first-parity sows . At 30 d of gestation , pregnant gilts were allotted based on BW to 1 of 2 diets supplemented with 1 % L-Arg . HCl or 1.7 % L-Ala ( isonitrogenous control ) . After farrowing , sows were further allotted based on BW within previous gestation treatment groups to 1 of 2 lactation diets supplemented with 1 % L-Arg . HCl or 1.7 % L-Ala ( isonitrogenous control ) . All gestation diets contained 3.1 Mcal/kg and 12.2 % CP ( as is ) and were fed 2 kg/d in 2 equally sized meals , whereas all lactation diets contained 3.2 Mcal/kg and 18.6 % CP ( as is ) and were fed ad libitum . Litter size was st and ardized to 10 piglets by cross-fostering within 24 h postfarrowing . On a weekly basis , BW and backfat ( BF ) thickness of sows , as well as piglet BW were measured , and blood and milk sample s were obtained from the sows . Number of days from weaning to estrus and ADFI were also recorded . There were no differences in BW , BF thickness , ADFI , or days until return to estrus among treatment groups . There was no effect of the gestation diet or a gestation x lactation diet interaction on any parameter measured . On d 7 of lactation , plasma concentrations of Arg and insulin in sows , as well as concentrations of most AA in milk , were greater ( P < 0.05 ) in response to Arg supplementation during lactation compared with the control . Weight gain of piglets from sows fed the Arg-supplemented diet during lactation was greater between d 0 and 7 ( P < 0.01 ) and between d 0 and 21 ( P < 0.05 ) of lactation compared with piglets from sows fed the control diet . Collectively , results from this study indicate the potential beneficial effects of dietary Arg supplementation in improving the lactation performance of first-parity sows Preweaning piglet mortality is largely attributed to the incidence of low birth weight and birth weight variation within the litter . Therefore , developing strategies to increase within-litter uniformity of piglet birth weight is important . This study investigated the effects of different feeding strategies based on specific nutrient supplies in sow diet on the within-litter variation of piglet birth weight ( BW0 ) . Four batches of highly prolific crossbred L and race × Large White sows were used . Three dietary treatments were compared : supplies of dextrose during the week before insemination ( 190 g/d ) and of L-arginine ( 25.5 g/d ) from d 77 of pregnancy until term ( DEXA , n = 26 ) ; a dietary supplementation of L-arginine only ( 25.5 g/d ) , from d 77 of pregnancy until term ( ARGI , n = 24 ) ; and no supplementation to a st and ard gestation diet ( CTL ; n = 23 ) . Total born piglets ( TB ) , i.e. , piglets born alive ( BA ) and stillborn piglets , were numbered and weighed at birth and at weaning . Data were analyzed by ANOVA using the MIXED procedure in a model that included dietary treatment ( ARGI , DEXA , and CTL ) , initial parity ( 1 , 2 and 3 , 4 , and more ) , and backfat thickness ( below or above the average value at the onset of the experiment : 15.7 mm ) as the main effects and batch as r and om effect . The treatment did not influence ( P > 0.10 ) the number of piglets at birth ( on average 15.6 ± 3.8 and 14.2 ± 3.6 for TB and BA , respectively ) or piglet BW0 ( on average 1.48 ± 0.26 and 1.50 ± 0.26 kg for TB and BA , respectively ) . The coefficient of variation of piglet BW0 ( CV(BW0 ) ) was less in litters from ARGI sows than in litters from CTL sows and intermediate in litters from DEXA sows ( for TB : 21.4 , 23.4 , and 25.7 % , P = 0.08 ; for BA : 20.6 , 22.5 , and 25.4 % , P = 0.03 , in the ARGI , DEXA , and CTL groups , respectively ) . Irrespective of diet , CV(BW0 ) was less ( P < 0.01 ) in litters with 16 TB piglets or less than in the largest litters ( 20.9 vs. 26.5 % ) . Litter growth rate during lactation and litter size at weaning were not influenced ( P > 0.10 ) by dietary treatments . In conclusion , supplementing gestation diet with L-arginine during the last third of pregnancy reduced within-litter variation of piglet birth weight . Combining L-arginine dietary supply with a supplementation of dextrose before insemination provided no additional benefit The efficiency of nutrient transport from the pregnant female pig to the developing fetus depends on the size and function of the placenta . It has been reported that maternal and fetal blood vessels are arranged in a cross-countercurrent arrangement within placental microscopic folds . Thus , the blood supplies are in close apposition to each other within these microscopic folds , and maternal and fetal blood flows in approximately opposite directions perpendicular to the plane of the placenta . This arrangement indicates that the width of the microscopic folds influences placental efficiency . The objective of this study was to determine whether differences in pig placental microscopic fold development are associated with differences in fetal size or are influenced by selection for ovulation rate or uterine capacity . Gilts from a r and omly selected control line , a line selected for ovulation rate , and a line selected for uterine capacity were slaughtered , and uterine wall sample s were collected within the placentas associated with the largest and smallest fetuses in each litter on d 45 , 65 , 85 , and 105 of gestation . The uterine wall sample s were processed for histology and analyzed using computer-assisted morphometry . Average width of the placental folds and average width of the placental stroma above the folds were measured . To measure fold complexity , the length of the epithelial bilayer for a given length of placenta was also measured . The width of the folded bilayer increased significantly from d 65 to 105 and was greater in placentas associated with small fetuses compared with large fetuses on d 105 of gestation . In contrast , the width of the placental stroma above the folded bilayer decreased with gestation and decreased more rapidly in placenta associated with the smallest compared with the largest fetus . These results indicate that the width of the microscopic folds of the placental trophoblast/endometrial epithelial bilayer is increased in placenta associated with small fetuses , which we hypothesize will increase the surface area for interaction between maternal and fetal blood supplies , thus improving placental efficiency in response to reduced placental size The objectives of this study were to investigate the potential mechanisms of dietary arginine ( Arg ) and N-carbamoylglutamate ( NCG ) supplementation on reproductive performance of sows . Twenty-seven crossbred ( L and race × Large White ) sows with similar body weight and parity at day ( 90±1 ) of gestation were assigned r and omly into 3 groups ( n=9 ) control group , Arg group , NCG group , and fed with the following diets : a control diet , and the control diet supplemented with 1.0 % Arg or 0.1 % NCG . Litter size was recorded . Blood sample s were obtained for biochemical analyses . Placenta chorioallantoic membrane tissue collected immediately after birth to preserve in RNA stabilizer for mRNA analysis of endothelial nitric oxide synthase ( eNOS ) , endothelial growth factor a ( VEGFA ) and placenta growth factor 1 ( PlGF1 ) by real time-PCR . The results showed that compared with the control group , the average birth weight of all piglets born alive were 16.2 % and 14.3 % higher in the Arg and NCG groups ( P<0.05 ) , respectively ; plasma VEGFA was higher in the Arg group ( P<0.05 ) . The expression of VEGFA in the allantochorion tissue of the NCG-supplemented group was higher ( P<0.01 ) , and tended to be higher in the Arg-supplemented group ( 0.05<P<0.1 ) . NCG significantly increased protein concentration of PlGF1 in plasma ( P<0.05 ) , and enhanced PlGF1mRNA expression in allantochorion tissue of placenta ( P<0.01 ) . The results suggested that dietary Arg and NCG supplementation play important roles in meliorating placental vascular function and promoting the nutrients supply to fetus |
12,896 | 23,480,971 | Overall , we found that PA interventions were effective for OW/OB pregnant as well as postpartum women .
In the subgroup analyses by PA intervention types , supervised PA plus diet interventions were the most effective .
CONCLUSIONS PA plus diet interventions may require more than advice ; supervised PA programs or personalized prescription/ goals are needed to prevent excessive weight gain for OW/OB pregnant women and excessive weight retention for OW/OB postpartum women | OBJECTIVE To review the effectiveness of physical activity ( PA ) and PA plus diet interventions in managing weight among overweight or obese ( OW/OB ) pregnant or postpartum women . | OBJECTIVE to examine the effect of individual counselling on diet and physical activity from pregnancy to six months post partum , or from birth to six months post partum , on weight retention among Taiwanese women . DESIGN a r and omised controlled trial assigned participants to two experimental groups [ from pregnancy to six months post partum ( EP ) and from birth to six months post partum ( EPP ) ] and one comparison group . SETTING a 3900-bed medical centre in northern Taiwan with around 3000 births annually . PARTICIPANTS a sample of 189 women who had regular check-ups during pregnancy and gave birth at the medical centre . INTERVENTIONS the comparison group received the routine outpatient department obstetric educational programme . The EP group attended regularly scheduled clinic visits with individualised dietary and physical activity education plans from 16 gestational weeks to six months post partum , and received on brochure . The EPP group received the same educational intervention as the EP group from 24 - 48 hours after birth to six months post partum . MEASUREMENTS body weight , body mass index , health-promoting behaviour and psycho-social variables ( self-efficacy , body image , depression and social support ) . FINDINGS average gestational weight gain was 14.02 , 15.27 and 16.22 kg in the three EP , EPP and comparison groups respectively , and average weight retention at six months post partum was 2.34 , 4.06 and 5.08 kg in the three groups , respectively . KEY CONCLUSIONS a diet and physical activity intervention from pregnancy is effective for reducing post-pregnancy weight retention . IMPLICATION S FOR PRACTICE the findings of the present study should be taken into consideration when incorporating significant others and weight-loss maintenance strategies with interventions for a healthier family lifestyle Background To evaluate the effectiveness and safety of water aerobics during pregnancy . Methods A r and omized controlled trial carried out in 71 low-risk sedentary pregnant women , r and omly allocated to water aerobics or no physical exercise . Maternal body composition and perinatal outcomes were evaluated . For statistical analysis Chi-square , Fisher 's or Student 's t-tests were applied . Risk ratios and their 95 % CI were estimated for main outcomes . Body composition was evaluated across time using MANOVA or Friedman multiple analysis . Results There were no significant differences between the groups regarding maternal weight gain , BMI or percentage of body fat during pregnancy . Incidence of preterm births ( RR = 0.84 ; 95%CI:0.28–2.53 ) , vaginal births ( RR = 1.24 ; 95%CI:0.73–2.09 ) , low birthweight ( RR = 1.30 ; 95%CI:0.61–2.79 ) and adequate weight for gestational age ( RR = 1.50 ; 95%CI:0.65–3.48 ) were also not significantly different between groups . There were no significant differences in systolic and diastolic blood pressure and heart rate between before and immediately after the water aerobics session . Conclusion Water aerobics for sedentary pregnant women proved to be safe and was not associated with any alteration in maternal body composition , type of delivery , preterm birth rate , neonatal well-being or weight Optimal strategies to prevent progression towards overt diabetes in women with recent gestational diabetes remain ill defined . We report a pilot study of a convenient , home based exercise program with telephone support , suited to the early post-partum period . Twenty eight women with recent gestational diabetes were enrolled at six weeks post-partum into a 12 week r and omised controlled trial of Usual Care ( n = 13 ) versus Supported Care ( individualised exercise program with regular telephone support ; n = 15 ) . Baseline characteristics ( Mean ± SD ) were : Age 33 ± 4 years ; Weight 80 ± 20 kg and Body Mass Index ( BMI ) 30.0 ± 9.7 kg/m2 . The primary outcome , planned physical activity { Median ( Range ) } , increased by 60 ( 0–540 ) mins/week in the SC group versus 0 ( 0–580 ) mins/week in the UC group ( P = 0.234 ) . Walking was the predominant physical activity . Body weight , BMI , waist circumference , % body fat , fasting glucose and insulin did not change significantly over time in either group . This intervention design ed to increase physical activity in post-partum women with previous gestational diabetes proved feasible . However , no measurable improvement in metabolic or biometric parameters was observed over a three month period Pregnant women at risk for preeclampsia may benefit from the positive effects of exercise , but they may be unlikely to adhere to an exercise program . A r and omized trial was conducted with 124 sedentary pregnant women to compare the effects of walking exercise to a stretching exercise on adherence and on the preeclampsia risk factors of heart rate ( HR ) , blood pressure , and weight gain . Walkers exercised less than stretchers both overall and as pregnancy advanced . HR and blood pressure were lower among stretchers than walkers , but weight gain did not differ between the groups . For sedentary pregnant women , a stretching exercise may be more effective than walking in mitigating the risk of preeclampsia due to higher adherence and possible cardiac-physiologic effects Please cite this paper as : Hui A , Back L , Ludwig S , Gardiner P , Sevenhuysen G , Dean H , Sellers E , McGavock J , Morris M , Bruce S , Murray R , Shen G. Lifestyle intervention on diet and exercise reduced excessive gestational weight gain in pregnant women under a r and omised controlled trial . BJOG 2012;119:70–77 AIM The significant deterioration of insulin sensitivity and glucose tolerance during pregnancy can have serious health implication s for both the pregnant woman and her baby . Although it is well established that regular exercise benefits insulin sensitivity in the nonpregnant population , the effect on glucose tolerance in obese pregnant women is not known . The purpose of this study was to investigate the effect of a supervised 10-week , home-based , exercise programme , beginning at week 18 of gestation , on glucose tolerance and aerobic fitness in previously sedentary obese women . METHODS Twelve sedentary obese women were r and omized into an exercise ( EX ; n=6 ) or control ( CON ; n=6 ) group at 18 weeks of gestation . Those r and omized to EX engaged in 10 weeks of supervised home-based exercise ( three sessions a week of stationary cycling ) , while those in the CON group maintained their usual daily activity . Their glucose and insulin responses to an oral glucose tolerance test ( OGTT ) , as well as their aerobic fitness , were assessed both pre- and postintervention . RESULTS Reduced glucose tolerance in the CON , but not EX , group was indicated by a tendency postintervention towards higher blood glucose levels at 1h of the OGTT ( P=0.072 ) . Furthermore , at 2h of the postintervention OGTT , blood glucose tended to remain elevated from baseline in the CON ( P=0.077 ) . There was also a trend towards increased fitness in the EX ( P=0.064 ) , but not the CON group . CONCLUSION Regular aerobic exercise begun during pregnancy may have favourable effects on glucose tolerance and fitness in obese women , and warrants further investigation in a larger sample population Flaws in the design , conduct , analysis , and reporting of r and omised trials can cause the effect of an intervention to be underestimated or overestimated . The Cochrane Collaboration ’s tool for assessing risk of bias aims to make the process clearer and more OBJECTIVE This paper describes the design and findings of a pilot Mothers In Motion ( P-MIM ) program . DESIGN A r and omized controlled trial that collected data via telephone interviews and finger stick at 3 time points : baseline and 2 and 8 months post-intervention . SETTING Three Special Supplemental Nutrition Program for Women , Infants , and Children ( WIC ) sites in southern Michigan . PARTICIPANTS One hundred and twenty nine overweight and obese African-American and white mothers , 18 - 34 years old . INTERVENTION The 10-week , theory-based , culturally sensitive intervention messages were delivered via a series of 5 chapters on a DVD and complemented by 5 peer support group teleconferences . MAIN OUTCOME MEASURES Dietary fat , fruit , and vegetable intake ; physical activity ; stress ; feelings ; body weight ; and blood glucose . ANALYSIS General linear mixed model was applied to assess treatment effects across 2 and 8 months post-intervention . RESULTS No significant effect sizes were found in primary and secondary outcome variables at 2 and 8 months post-intervention . However , changes in body weight and blood glucose showed apparent trends consistent with the study 's hypotheses . CONCLUSIONS AND IMPLICATION S The P-MIM showed promise for preventing weight gain in low-income overweight and obese women . However , a larger experimental trial is warranted to determine the effectiveness of this intervention Objective : We examined the effect of light intensity resistance exercise training performed during the second and third trimester of pregnancy on the newborn 's birth size . We also studied the association between maternal body weight prior to pregnancy and newborn 's birth size . Design : R and omised controlled trial . Subjects : We r and omly assigned 160 sedentary gravidae to either a training ( n=80 ) or a control ( n=80 ) group . The training programme focused on light resistance and toning exercises ( three times per week , 35–40 min per session ) . We recorded the Apgar score , birth weight , birth length , and head circumference of the newborn , as well as gestational age at time of delivery from hospital perinatal records . We also measured maternal weight and height before parity and gestational weight gain . Results : Maternal characteristics neither differed between groups ( all P>0.1 ) nor newborn characteristics ( all P>0.1 ) . Maternal body weight was positively and significantly associated with newborn 's birth weight and length only in the control group ( β=19.20 and 0.065 , respectively , P<0.01 ) . Conclusion : Light intensity resistance training performed over the second and third trimester of pregnancy does not have a negative impact on the newborn 's body size or overall health . Exercise interventions might attenuate the adverse consequences of maternal body weight before pregnancy on the newborn 's birth size OBJECTIVE This study examines the effects of circuit-type resistance training on the need for insulin in women with gestational diabetes mellitus . STUDY DESIGN Thirty-two patients with gestational diabetes mellitus were r and omly assigned either to a group that was treated with diet alone or to a group that was treated with diet plus resistance exercise . RESULTS The number of women whose condition required insulin therapy was the same , regardless of treatment . However , a subgroup analysis that examined only overweight women ( prepregnant body mass index , > 25 kg/m(2 ) ) showed a lower incidence of insulin use in the diet-plus-exercise group ( P<.05 ) . Women in the diet-plus-exercise group were prescribed less insulin ( P<.05 ) and showed a longer delay from diagnosis to the initiation of insulin therapy ( P<.05 ) , compared with the diet-alone group . CONCLUSION Resistance exercise training may help to avoid insulin therapy for overweight women with gestational diabetes mellitus BACKGROUND Maternal obesity and excessive gestational weight gain ( GWG ) are major short- and long-term risk factors for maternal and fetal complications . OBJECTIVE The objective was to study whether a lifestyle intervention based on a brochure or on active education can improve dietary habits , increase physical activity ( PA ) , and reduce GWG in obese pregnant women . DESIGN In this r and omized controlled trial , 195 white , obese pregnant women [ age : 29 + or - 4 y ; body mass index ( in kg/m(2 ) ) ; 33.6 + or - 4.2 ] were r and omly assigned into 3 groups : a group that received nutritional advice from a brochure , a group that received the brochure and lifestyle education by a nutritionist , and a control group . Nutritional habits were evaluated every trimester through 7-d food records . PA was evaluated with the Baecke question naire . RESULTS Energy intake did not change during pregnancy and was comparable in all groups . Fat intake , specifically saturated fat intake , decreased and protein intake increased from the first to the third trimester in the passive and active groups compared with an opposite change in the control group . Calcium intake and vegetable consumption increased during pregnancy in all groups . PA decreased in all groups , especially in the third trimester . No significant differences in GWG and obstetrical or neonatal outcome could be observed between the groups . CONCLUSIONS Both lifestyle interventions improved the nutritional habits of obese women during pregnancy . Neither PA nor GWG was affected Objective : To evaluate the effects of aerobic training on submaximal cardiorespiratory capacity in overweight pregnant women . Methods : We conducted a r and omized clinical trial in a referral center prenatal clinic during the period 2000–2002 . Of 132 overweight ( body mass index 26–31 kg/m2 ) but otherwise healthy volunteers , at 20 years of age or older , with gestational age of 20 weeks or less , and without diabetes or hypertension , 92 consented to participate and were r and omized . Intervention consisted of 3 one-hour aerobic exercise sessions per week ; the control group received weekly relaxation and focus group discussion s. The main outcome measure was submaximal exercise capacity evaluated by oxygen uptake at the anaerobic ( first ventilatory ) threshold during cardiopulmonary treadmill testing 12 weeks after r and omization . Results : Oxygen uptake at the anaerobic threshold increased 18 % ( 15.9 ± 2.6 to 18.1 ± 3.1 mL · min−1 · kg−1 ) in the exercise group but decreased 16 % ( 16.9 ± 3.0 to 15.8 ± 2.6 mL · min−1 · kg−1 ) among the control group . Oxygen consumption at the anaerobic threshold , adjusted through analysis of covariance for baseline oxygen uptake , was 2.68 ( 95 % confidence interval 1.23 to 4.12 ) mL · min−1 · kg−1 greater in the exercise group . Women in the exercise group were approximately 5 times more likely than those in the control group to have regular or good cardiorespiratory capacity ( 12/38 versus 2/38 ; relative risk 5.2 , 95 % confidence interval 1.2 to 22.0 , number needed to treat 5 ) . Conclusion : Aerobic training in overweight pregnant women substantially increases submaximal exercise capacity , overcoming the otherwise negative effects of pregnancy in this regard . Additional studies are required to evaluate its effect on major clinical outcomes . LEVEL OF EVIDENCE : Promoting weight loss among overweight low-income postpartum women has proven difficult . The study ’s aims were to pilot-test ethnic-specific weight-loss interventions using r and omized control-group design s for White/Anglo ( n = 23 ) , African American ( n = 25 ) , and Hispanic low-income postpartum women ( n = 23 ) and draw lessons from psychosocial data and follow-up interviews . Interventions lasting 13 weeks were offered in group setting s in the community . Similar to other r and omized trials with low-income mothers , weight changes between intervention and control groups were nonsignificant in each ethnic group ; however , changes correlated significantly with self-efficacy ( Spearman r = .50 ) for White/Anglo women and self-efficacy ( Spearman r = −.48 ) and perceived stress ( Spearman r = .48 ) for African American women . In follow-up interviews , women felt interventions gave a good foundation for weight loss , but program and situational factors affected participation and weight loss . Control groups ( mailed interventions later ) were generally more pleased with their assignment than intervention groups BACKGROUND : The Institute of Medicine ( IOM ) recommends that normal‐weight women ( BMI ( body mass index ) of 19.8–26.0 ) gain 25–35 lb ( 11.4–15.9 kg ) during pregnancy , and that overweight women ( BMI of 26.1–29.0 ) gain 15–25 lbs ( 6.8–11.4 kg ) . A significant number of normal‐weight women and an even greater proportion of overweight women exceed these guidelines , which increases postpartum weight retention and may contribute to the development of obesity . OBJECTIVE : To determine whether a stepped care , behavioral intervention will decrease the percentage of women who gain more than the IOM recommendation . DESIGN : R and omized controlled trial comparing a stepped-care behavioral intervention with usual care . Women ( n=120 ) who had a BMI > 19.8 , age>18 and < 20 weeks gestation were recruited from a hospital-based clinic serving low-income women and r and omized by race and BMI category to the intervention or control group . The intervention group received education about weight gain , healthy eating , and exercise and individual graphs of their weight gain . Those exceeding weight gain goals were given more intensive intervention . Women were followed through pregnancy to their first postpartum clinic visit . The main outcome measure was weight gain during pregnancy categorized as above the IOM recommendations vs below or within the IOM recommendations . RESULTS : The intervention significantly decreased the percentage of normal-weight women who exceeded the IOM recommendations ( 33 vs 58 % , P<0.05 ) . There was a non-significant ( P=0.09 ) effect in the opposite direction among overweight women ( 59 % of intervention and 32 % of control gained more than recommended ) . Postpartum weight retention was strongly related to weight gain during pregnancy ( r=0.89 ) . CONCLUSIONS : The intervention reduced excessive weight gain during pregnancy among normal weight women OBJECTIVE The objective of this study was to estimate the effects of low and high gestational weight gain , in different maternal Body Mass Index ( BMI ) classes , on obstetric and neonatal outcomes . METHOD A prospect i ve population -based cohort study of 245,526 singleton term pregnancies . Women were grouped in five categories of BMI and in three gestational weight gain categories ; < 8 kg ( low weight gain ) , 8 - 16 kg and > 16 kg ( high weight gain ) . Obstetric and neonatal outcomes were evaluated after adjustments for maternal age , parity , smoking , year of birth . RESULT Obese women with low gestational weight gain had a decreased risk for the following outcomes ( adjusted odds ratio ; 95 % confidence interval ) : preeclampsia ( 0.52 ; 0.42 - 0.62 ) , cesarean section ( 0.81 ; 0.73 - 0.90 ) , instrumental delivery ( 0.75 ; 0.63 - 0.88 ) , and LGA births ( 0.66 ; 0.59 - 0.75 ) . There was a 2-fold increased risk for preeclampsia and LGA infants among average and overweight women with excessive weight gain . High gestational weight gain increased the risk for cesarean delivery in all maternal BMI classes . CONCLUSION The effects of high or low gestational weight gain differ depending on maternal BMI and the outcome variable studied . Obese women may benefit from a low weight gain during pregnancy BACKGROUND The retention of weight gained during pregnancy may contribute to obesity . Lactation should promote weight loss , but weight loss is highly variable among lactating women . The risks associated with the restriction of energy intake during lactation have not been adequately evaluated . The purpose of this study was to determine whether weight loss by women during lactation affects the growth of their infants . METHODS We r and omly assigned 40 breast-feeding women who were overweight ( defined as a body-mass index [ the weight in kilograms divided by the square of the height in meters ] of 25 to 30 ) at 4 weeks post partum either to restrict their energy intake by 500 kcal per day and to exercise for 45 minutes per day for 4 days per week ( the diet- and -exercise group ) or to maintain their usual dietary intake and not exercise more than once per week for 10 weeks ( the control group ) . We measured the weight and fat mass of the women and the weight and length of the infants before , during , and at the end of the study period . RESULTS The mean ( + /-SD ) energy intake decreased by 544+/-471 kcal per day in the diet- and -exercise group . As compared with the control group , the women in the diet- and -exercise group lost more weight ( 4.8+/-1.7 kg vs. 0.8+/-2.3 kg , P<0.001 ) and fat mass ( 4.0+/-2.0 kg vs. 0.3+/-1.8 kg , P<0.001 ) . The gains in weight and length of the infants whose mothers were in the diet- and -exercise group ( 1925+/-500 g and 7.8+/-2.0 cm , respectively ) were not significantly different from those of the infants whose mothers were in the control group ( 1861+/-576 g and 7.3+/-1.7 cm ) . CONCLUSIONS Weight loss of approximately 0.5 kg per week between 4 and 14 weeks post partum in overweight women who are exclusively breast-feeding does not affect the growth of their infants BACKGROUND Postpregnancy weight retention contributes to the near-epidemic prevalence of obesity in the United States . This study examines the impact of an individualized , structured diet and physical activity intervention on weight loss in overweight women during the first year postpartum . METHODS Forty overweight postpartum women were r and omized to either a structured ( STR ) or a self-directed ( SELF ) intervention . Measurements included body weight , percent body fat , daily caloric intake , habitual physical activity , and cardiorespiratory fitness . Subjects in STR received individualized diet and physical activity prescriptions derived from baseline measurements . They met weekly for the first 12 weeks and kept daily food and activity diaries . Subjects in SELF received a single 1-hour educational session about diet and activity . RESULTS Only 23 of 40 participants remained in the study at 1 year postpartum . Of those , STR ( n = 13 ) had a significant weight loss ( 7.3 kg , p < 0.01 ) , a significant decrease in percent body fat ( 6 % , p < 0.01 ) , and no change in fat-free mass . SELF ( n = 10 ) had no significant change in weight , percent body fat , or fat-free mass . CONCLUSIONS Women who committed to this one class per week for 12 weeks postpartum had a high likelihood of successful weight loss that persisted at 1 year . Women who were overweight before pregnancy were unlikely to lose the pregnancy-related weight without the help of a formal intervention . This suggests that healthcare professionals should strongly encourage postpartum women to enroll in a structured diet and exercise program PURPOSE Women who are unable to return to a healthy weight by 6 months postpartum increase their risk factors for the development of chronic disease ( CD ; including metabolic syndrome , obesity , and cardiovascular disease ) . In a prospect i ve r and omized intervention study , we examined the effect of exercise intensity on risk factors for CD in the postpartum . We hypothesized that women receiving an intervention targeting healthy weight loss would have improved CD risk factors compared with women not receiving the intervention . Further , we hypothesized that nutrition control and moderate-intensity exercise would have the greatest improvement in CD risk factors versus low-intensity exercise . METHODS Women were r and omly assigned to a nutrition plus low-intensity ( 30 % HR reserve ; n = 20 ) or moderate-intensity ( 70 % HR reserve ; n = 20 ) exercise intervention group . The program consisted of supervised walking for 45 min , three to four times per week for 16 wk . All women were screened for CD at the beginning ( 7 - 8 wk postpartum ) and at the end ( 23 - 25 wk postpartum ) of the study . A historical control group of 20 sedentary postpartum women was matched by body mass index , age , and parity . RESULTS The low- and moderate-intensity groups lost more body mass ( -4.2 ± 4.0 and -5.0 ± 2.9 kg , respectively ) compared with the control group ( -0.1 ± 3.3 kg , P < 0.01 ) . Plasma low-density lipoprotein was reduced for the low- and moderate-intensity groups ( -0.29 ± 0.21 and -0.28 ± 0.17 mmol · L ) compared with the control group ( 0.03 ± 0.18 mmol · L , P = 0.015 ) . In addition , glucose concentrations were reduced and adiponectin concentrations increased ( P = 0.037 ) , regardless of exercise intensity , although the sedentary controls remained unchanged or at increased risk for CD . CONCLUSIONS Women receiving a postpartum intervention targeting healthy weight loss , regardless of exercise intensity , improved CD risk factors compared with women not receiving the intervention INTRODUCTION Exercise during pregnancy is associated with reduced rates of preeclampsia , gestational diabetes , anxiety , insomnia , and excessive weight gain . Continued exercise during the postpartum period is important for healthy weight loss and reduced anxiety . Unfortunately , pregnant and postpartum women are significantly less active than nonpregnant women . The purpose of this pilot study was to evaluate a telephone-based exercise intervention design ed for pregnant and postpartum women . METHODS Healthy women ( N = 37 ) who were pregnant ( 16 weeks ' gestation or less ) or postpartum ( 6 months or less ) participated in a 3-month , telephone-based exercise intervention based on the transtheoretical model and social cognitive theory . Exercise was assessed by using the 7-Day Physical Activity Recall Interview . RESULTS Pregnant participants significantly increased their exercise from a mean ( st and ard deviation [ SD ] ) of 60.47 ( 63.1 ) minutes per week at baseline to 132.9 ( 82.3 ) minutes at 3 months , F(1,13 ) = 9.96 , P < .01 . Postpartum participants significantly increased their exercise from a mean ( SD ) of 68.9 ( 63.5 ) minutes per week at baseline to 123.8 ( 48.8 ) minutes at 3 months , F(1,15 ) = 6.56 , P < .05 . DISCUSSION Participants responded positively to the intervention by significantly increasing their exercise levels . There is a need for a large , r and omized controlled trial examining the efficacy of telephone-based exercise interventions for pregnant and postpartum women BACKGROUND A high prevalence of gestational diabetes mellitus and type 2 diabetes has been observed among the Cree of James Bay , Quebec . To address this problem , a diet and activity intervention during pregnancy , which was based on social learning theory , was initiated in 4 Cree communities . METHODS A prospect i ve intervention compared dietary , weight and glycemic indicators for 107 control subjects and for 112 women who received the intervention during the course of their pregnancy . A control period in 4 communities ( July 1995-March 1996 ) was followed by an intervention period ( April 1996-January 1997 ) when subjects were offered regular , individual diet counselling , physical activity sessions and other activities related to nutrition . RESULTS The intervention and control groups did not differ at baseline regarding their mean age ( 24.3 years [ SD 6.29 ] v. 23.8 years [ SD 5.86 ] ) , mean prepregnancy weight ( 81.0 kg [ SD 19.46 ] v. 78.9 kg [ SD 17.54 ] ) and mean gestational age at recruitment ( 17.1 weeks [ SD 7.06 ] v. 18.5 weeks [ SD 6.92 ] ) . The intervention did not result in differences in diet measured at 24 - 30 weeks ' gestation , rate of weight gain over the second half of pregnancy ( 0.53 kg per week [ SD 0.32 ] v. 0.53 kg per week [ SD 0.27 ] ) or plasma glucose level ( 50 g oral glucose screen ) between 24 and 30 weeks ( 7.21 mmol/L [ SD 2.09 ] v. 7.43 mmol/L [ SD 2.10 ] ) . Mean birth weights were similar ( 3741 g [ SD 523 ] v. 3686 g [ SD 686 ] ) , as was maternal weight at 6 weeks post partum ( 88.1 kg [ SD 16.8 ] v. 86.4 kg [ SD 19.0 ] ) . The only changes in dietary intake were a reduction in caffeine ( pregnancy ) and an increase in folate ( post partum ) . INTERPRETATION This intervention had only a minor impact on diet ; finding ways of encouraging appropriate body weight and activity levels remains a challenge Background Annual prevalence of gestational diabetes mellitus ( GDM ) is 12.5 % among Finnish pregnant women . The prevalence is expected to rise with the increasing overweight among women before pregnancy . Physical activity and diet are both known to have favourable effects on insulin resistance and possibly on the risk of GDM . We aim ed to investigate , whether GDM can be prevented by counseling on diet , physical activity and gestational weight gain during pregnancy . Methods / Design A cluster-r and omized controlled trial was conducted in 14 municipalities in the southern part of Finl and . Pairwise r and omization was performed in order to take into account socioeconomic differences . Recruited women were at 8 - 12 weeks ' gestation and fulfilled at least one of the following criteria : body mass index ≥ 25 kg/m2 , history of earlier gestational glucose intolerance or macrosomic newborn ( > 4500 g ) , age ≥ 40 years , first or second degree relative with history of type 1 or 2 diabetes . Main exclusion criterion was pathological oral glucose tolerance test ( OGTT ) at 8 - 12 weeks ' gestation . The trial included one counseling session on physical activity at 8 - 12 weeks ' gestation and one for diet at 16 - 18 weeks ' gestation , and three to four booster sessions during other routine visits . In the control clinics women received usual care . Information on height , weight gain and other gestational factors was obtained from maternity cards . Physical activity , dietary intake and quality of life were followed by question naires during pregnancy and at 1-year postpartum . Blood sample s for lipid status , hormones , insulin and OGTT were taken at 8 - 12 and 26 - 28 weeks ' gestation and 1 year postpartum . Workability and return to work were elicited by a question naire at 1- year postpartum . Linkage to the national birth register of years 2007 - 2009 will provide information on perinatal complications and GDM incidence among the non- participants of the study . Cost-effectiveness evaluation will be based on quality -adjusted life years . This study has received ethical approval from the Ethical board of Pirkanmaa Hospital District . Discussion The study will provide information on the effectiveness and cost-effectiveness of gestational physical activity and dietary counseling on prevention of GDM in a risk group of women . Also information on the prevalence of GDM and postpartum metabolic syndrome will be gained . Results on maintaining the possible health behaviour changes are important in order to prevent chronic diseases such as cardiovascular disease and diabetes . Trial registration The trial is registered IS RCT N BACKGROUND Excessive weight gain during pregnancy is a major risk factor for postpartum weight retention and future weight gain and obesity in women , but few adequately powered r and omized controlled trials have examined the efficacy of a behavioral weight-control intervention during pregnancy . OBJECTIVE This study examined whether a behavioral intervention during pregnancy could decrease the proportion of women who exceeded the 1990 Institute of Medicine ( IOM ) recommendations for gestational weight gains and increase the proportion of women who returned to pregravid weights by 6 mo postpartum . DESIGN This study was a r and omized , assessor-blind , controlled trial . Participants were pregnant ( 13.5 wk gestation ) , normal-weight ( NW ; n = 201 ) and overweight or obese ( OW/OB ; n = 200 ) women whose average age was 28.8 y. Participants were r and omly assigned within the 1990 IOM weight category ( NW compared with OW/OB ) to st and ard care ( n = 200 ) or to a behavioral intervention to prevent excessive gestational weight gain ( n = 201 ) . The intervention included one face-to-face visit ; weekly mailed material s that promoted an appropriate weight gain , healthy eating , and exercise ; individual graphs of weight gain ; and telephone-based feedback . The retention at the 6-mo postpartum assessment was 82 % . RESULTS Intent-to-treat analyses showed that the intervention , compared with st and ard care , decreased the percentage of NW women who exceeded IOM recommendations ( 40.2 % compared with 52.1 % ; P = 0.003 ) and increased the percentages of NW and OW/OB women who returned to their pregravid weights or below by 6 mo postpartum ( 30.7 % compared with 18.7 % ; P = 0.005 ) . CONCLUSION A low-intensity behavioral intervention during pregnancy reduced excessive gestational weight gains in NW women and prevented postpartum weight retention in NW and OW/OB women . This trial was registered at clinical trials.gov as NCT01117961 |
12,897 | 22,126,845 | Level of prior experience and availability of practice reinforcement influenced learning .
Participative and interactive learning strategies were predominantly used along with discussion of case scenarios .
Conclusions : Classroom-based education and training is useful for enhancing professionals ’ skills and perceived preparedness for delivering end-of-life care but should be reinforced by actual practice experience | Background : Staff from a range of health and social care professions report deficits in their knowledge and skills when providing end-of-life and palliative care , and education and training has been advocated at a range of levels .
Aims : To review the literature related to classroom-based and distance learning education and training initiatives for health and social care staff in end-of-life and palliative care , in terms of their target audience , extent , modes of delivery , content and teaching and learning strategies , and to identify the most effective educational strategies for enhancing care . | We describe training in CBT techniques for 20 palliative care practitioners delivered as 12 days ' equivalent teaching plus skills-building supervision over a six month period . Audiotapes of trainees ' interactions with patients during their usual work were rated using a specially devised ‘ Cognitive First Aid ’ rating scale ( CFARS ) . The CFARS was highly internally consistent ( Cronbach 's Alpha 0.93 ) and inter-rater reliability was high . Trainees showed significant gain in CBT skills competency over six months ( p=0.001 ) . After initial training , half the trainees were r and omised to discontinue supervision ; their measured CBT skill dropped as did their self-reported confidence when reassessed six months later , whereas those who continued in supervision gained further skill and maintained confidence ( p=0.007 ) . Palliative care practitioners can be trained in CBT skills by a simple and brief training course and supportive , skills-building supervision . These skills are compatible with national guidelines on delivery of psychological support to patients at all stages of cancer . Supervision is necessary to ensure maintenance of skills and confidence to use them AIMS To evaluate the effects of a palliative care education programme on the self-reported knowledge and confidence of 72 community nurses . DESIGN a prospect i ve longitudinal postal question naire survey was conducted . FINDINGS seventy-one ( 99 % ) completed a pre-course question naire , 52 ( 72 % ) a question naire at completion of the course , and 37 ( 51 % ) a question naire one year later . Following the programme , more nurses felt that their professional needs were being met well or very well . Confidence in practice showed an increasing trend over time . Desire for education was lower on course completion than at its start . Palliative Care Nursing Quiz scores rose from a pre-course median of 12.5 to 15 at course completion ( P=0.001 ) which was maintained 1 year later . CONCLUSION the education programme was successful in raising st and ards of knowledge , professional development and confidence . Improvement was maintained one year later The effect of a program to train clinicians to support patients making decisions about place of end-of-life care was evaluated . In all , 88 oncology and /or palliative care nursing and allied health providers from three Ontario health networks were r and omly assigned to an education or control condition . Quality of decision support provided to st and ardized patients was measured before and after training , as were participants ’ perceptions about the acceptability of the training program and their intentions to engage in patient decision support . Compared to controls , intervention group members improved the quality of decision support provided and were more likely to address a wider range of decision-making needs . Intervention group members scored higher on a knowledge test of decision support than controls and rated the components as acceptable . Improvements in the quality of decision support can be made by providing training and practical tools such as a patient decision aid OBJECTIVES To determine if an educational program can improve knowledge and attitude among ancillary staff on end-of-life care issues in a long-term care facility . DESIGN A pilot study using a pre- and post-test design prior to and at the completion of an education intervention . SETTING A long-term care facility in suburban Philadelphia that has 150 assisted living beds and 53 nursing home beds . PARTICIPANTS Long-term care ancillary staff including certified nursing assistants ( called " care managers " at this facility ) , social workers , recreational therapists , and food service workers . INTERVENTION The intervention was a novel educational program consisting of five in-service lectures with accompanying take home self- study modules for ancillary staff in long-term care entitled " Dignity in Dementia . " MEASUREMENTS Ancillary staff attitudes and knowledge on end-of-life issues in dementia were assessed with a knowledge and attitude question naire pre- and post-intervention . One-year follow-up question naires were administered to assess long-term maintenance of knowledge and attitude changes . RESULTS Thirty-two ancillary staff completed the pre-intervention question naires . Twenty-nine ancillary staff completed the post-intervention question naires ( 90.6 % ) . There was a significant change in the end-of-life knowledge level of the ancillary staff ( P = .0270 ) . Specifically , there was a significant change in one question dealing with dementia as a terminal disease ( P = .006 ) . There were also significant changes in the average attitude scores of the ancillary staff . ( P = .0242 ) . One-year follow-up revealed that both knowledge and attitude changes were maintained . CONCLUSIONS This pilot project demonstrates that a staff educational program on end-of-life care for dementia residents can improve end-of-life knowledge and attitudes among long-term care ancillary staff and that this improvement can be maintained for up to 1 year . This intervention is easily reproducible in the long-term care setting . This project is an important step in helping improve end-of-life care for dementia residents in long-term care setting s by improving the knowledge and attitudes of their caregivers Prompted by directives from the GMC , ‘ care of the dying ’ is identified as ‘ core curricula ’ for undergraduate medical education . However , there are many technical and interpersonal challenges faced in learning the practice of palliative medicine . Accordingly , the design and delivery of education programmes need to be both carefully considered and evaluated . Using B and ura ’s Social Cognitive Theory as a driver , appropriate methodology for evaluating a novel education programme in palliative medicine was drafted . A pre- and post-survey of an education programme and palliative care placement for fourth year medical undergraduate students from Liverpool University ( n = 216 ) was completed using a composite question naire containing ; i ) Self-efficacy in Palliative Care Scale ( SEPC ) and ii ) Thanatophobia Scale . Both scales have shown reliability and validity within the sample population . Additionally , a r and omly selected Focus Group was conducted to provide qualitative information on the students ’ experience . A total of 139 pre- and post- question naires ( 64 % ) were completed . Analysis identified significant improvements in perceived efficacy ( SEPC Communication t = −16.41 , P < 0.001 ; SEPC Patient Management t = −22.31 , P < 0.001 ; SEPC Multidisciplinary Teamwork t = −15.56 , P < 0.001 ) . Significant improvements in thanatophobia were also recorded ( z = −7.51 , P < 0.001 ) although some interesting anomalies were noted . This study demonstrates that considered and appropriately structured clinical education has been shown to significantly improve students ’ belief in their ability to practice palliative medicine and to improve their attitude towards care . In accordance with the study ’s theoretical driver , it is reasonable to propose that the engaged active learning will have a positive effect on the future care of dying patients Purpose High- quality palliative care requires physicians who communicate effectively , yet many do not receive adequate training . Leading efforts to demonstrate the effectiveness of such training have involved time-intensive programs that included primarily attending physicians , which have been conducted outside of the United States . The goal was to evaluate the effect of a short course to improve residents ' communication skills delivering bad news and eliciting patients ' preferences for end-of-life care . Method This prospect i ve trial enrolled internal medicine residents at Duke University Medical Center from 1999 to 2001 . The course consisted of small-group teaching with lecture , discussion , and role-play . The outcome measure was observed communication skills delivering bad news and eliciting patients ' preferences for end-of-life treatment , assessed via audio-recorded st and ardized patient encounters before and after receiving the intervention . Results Thirty-seven residents received the intervention and 19 were in the control group . Residents attending the course demonstrated statistically significant increases in their overall skill ratings in the delivery of bad news , with improvement in the specific areas of information giving and responding to emotional cues . Although cumulative scores for discussion s about patient preferences for treatment did not increase , residents demonstrated enhanced specific skills including discussing probability , presenting clinical scenarios , and asking about prior experience with end-of-life decision making . Conclusion A relatively short , intensive course can improve the end-of-life communication skills of U.S. medical residents The aim of this controlled study was to evaluate a 1-year learner-centred educational project in end-of-life care for home care staff in a rural district of Sweden . Another rural district in the same region served as a control area . A 20-item question naire measuring attitudes towards end-of-life care was design ed , and the Hospital Anxiety and Depression ( HAD ) scale was used to measure mental well being . Increased agreement to 18 of 20 attitude statements was seen in the education group , while 2 of 20 items showed a decreased agreement in the control group . Test retest reliability of the 20-item question naire was good ( r = 0.92 ) . The total HAD score decreased from 8.3 pretest to 5.3 post-test in the education group ( 95 % CI=2.1– 3.7 ; P<0.001 ) , and was 6.8 for both years in the control group . Our study shows that a comprehensive educational programme not only improved attitudes towards end-of-life care , but also the mental well being of the home care staff AIM This paper is a report of part of an evaluation of the impact of a national palliative care education and support programme on the knowledge and confidence of members of district nursing teams . BACKGROUND District nursing teams are the mainstay of ' h and s on ' provision of care at home . In recognition of their central role , the English Department of Health commissioned a national palliative care education programme as post registration education had been limited . METHODS The evaluation , conducted between 2002 and 2004 , had a mixed methods design . In the summative component , 1280 nurses were r and omly selected from eight cancer networks to receive postal question naires 1 year apart , before and after the educational intervention . Changes in scores were calculated and a multiple regression analysis undertaken to identify predictors of improvement in confidence in competence and knowledge . The formative component involved qualitative interviews with a sub- sample of 39 district nurses participating in the programme . FINDINGS Nurses who responded in both years ( 374/32 % ) were included in the analysis . There was a small statistically significant increase in confidence in palliative care competency and knowledge after participation in the educational programmes . Nurses without district nursing qualifications and who had never worked in specialist palliative care had the largest improvements in scores . Qualitative data supported these findings . CONCLUSION The findings suggest that the education programme led to improvements in self-reported district nursing confidence in palliative care competencies and knowledge ; it is likely that the baseline level of palliative care confidence in competency and knowledge has as a result been raised nationally |
12,898 | 16,968,383 | RESULTS From a series of split-mouth studies , it could be concluded that both an increase in surface roughness above the R(a ) threshold of 0.2 microm and /or of the surface-free energy facilitates biofilm formation on restorative material s. When both surface characteristics interact with each other , surface roughness was found to be predominant .
The biofilm formation is also influenced by the type ( chemical composition ) of bio material or the type of coating .
Extrapolation of data from studies on different restorative material s seems to indicate that transmucosal implant surfaces with a higher surface roughness/surface free energy facilitate biofilm formation | BACKGROUND From an ecological viewpoint , the oral cavity , in fact the oro-pharynx , is an ' open growth system ' .
It undergoes an uninterrupted introduction and removal of both microorganisms and nutrients .
In order to survive within the oro-pharyngeal area , bacteria need to adhere either to the soft or hard tissues in order to resist shear forces .
The fast turn-over of the oral lining epithelia ( shedding 3 x/day ) is an efficient defence mechanism as it prevents the accumulation of large masses of microorganisms .
Teeth , dentures , or endosseous implants , however , providing non-shedding surfaces , allow the formation of thick biofilms .
In general , the established biofilm maintains an equilibrium with the host .
An uncontrolled accumulation and /or metabolism of bacteria on the hard surfaces forms , however , the primary cause of dental caries , gingivitis , periodontitis , peri-implantitis , and stomatitis .
OBJECTIVES This systematic review aim ed to evaluate critically the impact of surface characteristics ( free energy , roughness , chemistry ) on the de novo biofilm formation , especially in the supragingival and to a lesser extent in the subgingival areas . | THE STUDY ASSESSES IN VIVO the surface roughness necessary to reduce plaque colonization on titanium after 24 hours . Three groups of 16 titanium disks were assigned to 3 different polishing groups ( A , B , and C ) . The roughness was evaluated with a laser profilometer and the morphology with a scanning electron microscope ( SEM ) . Eight volunteers were enrolled and two stents were applied in the m and ibular posterior region of each . Each stent supported 3 disks , one per group . The volunteers suspended oral hygiene for 24 hours , after which the stents were removed ; one was processed for evaluation of the adherent biomass and the other for SEM study . On each specimen a global area of 100 x 125 microns was examined with SEM . The area was composed of five 20 x 25 microns r and omly selected fields . For each field the density of bacteria and the morphotypes were recorded . The data quoted for the global area are cumulative of those observed in the 20 x 25 microns fields . Group A had a significantly smoother surface than groups B and C. The adherent microbial biomass determination and SEM evaluation revealed that group A contained less bacteria than the roughest group . The bacterial population was composed of cocci in group A , and of cocci and short and long rods in groups B and C. We conclude that a titanium surface with Ra < or = 0.088 microns and Rz < or = 1.027 microns strongly inhibits accumulation and maturation of plaque at the 24-hour time period and that such smoothness can be achieved in transgingival and healing implant components BACKGROUND Periodontitis and peri-implantitis are linked to the presence of several key pathogens . The treatment of these infectious processes therefore involves the reduction/eradication of bacteria associated with periodontitis . METHODS This prospect i ve , split-mouth , single-blind study followed the colonization of ' pristine ' sulci created in 42 partially edentulous patients during implant surgery ( e.g. abutment connection ) . The hypothesis was that the composition of the maturing subgingival plaque in these ' fresh ' peri-implant pockets would soon ( within 2 weeks ) be comparable to the subgingival microbiota of teeth with similar clinical parameters ( reference sites ) , including the presence of bacteria associated with periodontitis . Per patient , four subgingival plaque sample s were taken from shallow and medium pockets around implants ( test sites ) , and teeth within the same quadrant ( undisturbed microbiota as control sites ) , 1 , 2 , 4 , 13 , 26 and 78 weeks after abutment connection , respectively . The sample s were analysed by either checkerboard DNA-DNA hybridization , or cultural techniques , or real-time polymerase chain reaction ( PCR ) for intra-subject comparisons ( teeth vs. implant , for comparable probing depths ) . RESULTS Checkerboard DNA-DNA hybridization and real-time PCR revealed a complex microbiota ( including several pathogenic species ) in the peri-implant pockets within 2 weeks after abutment connection . After 7 days , the detection frequency for most species ( including the bacteria associated with periodontitis ) was already nearly identical in sample s from the fresh peri-implant pockets ( 5 % and 20 % of the microbiota belonging to red and orange complex , respectively ) when compared with sample s from the reference teeth . Afterwards ( e.g. between weeks 2 and 13 ) , the number of bacteria in peri-implant pockets only slightly increased ( + /-0.1 log value ) , with minor changes in the relative proportions of bacteria associated with periodontitis ( 8 % and 33 % of the microbiota belonging to red and orange complex , respectively ) . Although small differences were seen between teeth and implants at week 2 with cultural techniques , a striking similarity in subgingival microbiota was found with this technique from month 3 on , with nearly identical detection frequencies for bacteria associated with periodontitis for both abutment types . CONCLUSIONS This study indicates that the initial colonization of peri-implant pockets with bacteria associated with periodontitis occurs within 2 weeks BACKGROUND : If an implant with a rough surface is exposed to the oral cavity , it may accumulate greater amounts of plaque than a smooth surface , which may lead to severe problems with mucositis and peri-implantitis . The purpose of the present paper was to investigate the early inflammatory response to mucosa-penetrating abutments prepared with varying surface roughness . METHODS : Nine patients had all five of their original abutments exchanged to test abutments for a 4-week period . The test abutments were prepared with five different roughnesses . The surface roughness was measured with an optical profilometer . At the end of the test period , clinical evaluation was performed ; the health of the surrounding mucosa , the amount of accumulated plaque and marginal bleeding were registered . One biopsy was taken from each test abutment . Qualitative and quantitative histological evaluations were performed . RESULTS : There was a statistically significant difference between patients regarding the amount of accumulated plaque on the abutment surfaces and inflammatory cells , but no difference between the surface modifications in relation to plaque accumulation or number of inflammatory cells . CONCLUSION : No relation was found between inflammatory response and abutment surface roughness after an evaluation time of 4 weeks in a human test model The roughness of intraoral hard surfaces plays an important role in bacterial adhesion and colonization . Earlier studies have shown that rough surfaces accumulate up to 25 times more subgingival plaque than do smooth sites . In the present study , the influence of surface smoothing was studied . In six partially edentulous patients waiting for a fixed prosthesis supported by endosseous titanium implants , four titanium abutments with different surface roughness were r and omly placed . After 1 month of intraoral exposure , subgingival plaque sample s from each abutment were compared within each patient by means of differential phase-contrast microscopy . After 3 months , supragingival and subgingival plaque sample s were taken from all abutments for differential phase-contrast microscopy and culturing . Probing depth , recession , and bleeding upon probing were scored at the same visit . Differential phase-contrast microscopy showed that subgingivally , only the two roughest abutments harbored spirochetes after 1 month . After 3 months , subgingivally , the composition of the flora showed little variation on the different abutment types , although spirochetes were only noticed around the roughest abutments . Anaerobic culturing result ed in comparable amounts of colony-forming units for all abutment types , both supragingivally and subgingivally . Subgingivally , the microbiologic composition did not show major interabutment differences . Clinical ly , small differences in probing depth were observed . The roughest abutment showed some attachment gain ( 0.2 mm ) during 3 months , whereas all other abutments had an attachment loss ranging from 0.8 to greater than 1 mm . The results indicate that a reduction in surface roughness ( less than a roughness of 0.2 micron ) had no major effect on the microbiologic composition , supragingivally or subgingivally . These observations indicate the existence of a threshold roughness below which no further impact on the bacterial adhesion and /or colonization should be expected . However , clinical evaluation seems to indicate that a certain surface roughness is necessary for increased resistance to clinical probing Bacterial adhesion to intra-oral , hard surfaces is firmly influenced by the surface roughness to these structures . Previous studies showed a remarkable higher subgingival bacterial load on rough surfaces when compared to smooth sites . More recently , the additional effect of a further smoothening of intra-oral hard surfaces on clinical and microbiological parameters was examined in a short-term experiment . The results indicated that a reduction in surface roughness below R(a ) = 0.2 microns , the so-called " thresholds R(a ) " , had no further effect on the quantitative/qualitative microbiological adhesion or colonisation , neither supra- nor subgingivally . This study aims to examine the long-term effects of smoothening intra-oral hard transgingival surfaces . In 6 patients expecting an overdenture in the lower jaw , supported by endosseus titanium implants , 2 different abutments ( transmucosal part of the implant ) : a st and ard machined titanium ( R(a ) = 0.2 microns ) and one highly polished and made of a ceramic material ( R(a ) = 0.06 microns ) were r and omly installed . After 3 months of intra-oral exposure , supra- and subgingival plaque sample s from both abutments were compared with each other by means of differential phase-contrast microscopy ( DPCM ) . Clinical periodontal parameters ( probing depth , gingival recession , bleeding upon probing and Periotest-value ) were recorded around each abutment . After 12 months , the supra- and subgingival sample s were additionally cultured in aerobic , CO2-enriched and anaerobic conditions . The same clinical parameters as at the 3-month interval were recorded after 12 months . At 3 months , spirochetes and motile organisms were only detected subgingivally around the titanium abutments . After 12 months , however , both abutment-types harboured equal proportions of spirochetes and motile organisms , both supra- and subgingivally . The microbial culturing ( month 12 ) failed to detect large inter-abutment differences . The differences in number of colony- forming units ( aerobic and anaerobic ) were within one division of a logarithmic scale . The aerobic culture data showed a higher proportion of Gram-negative organisms in the subgingival flora of the rougher abutments . From the group of potentially " pathogenic " bacteria , only Prevotella intermedia and Fusobacterium nucleatum were detected for anaerobic culturing and again the inter-abutment differences were negligible . Clinical ly , the smoothest abutment showed a slightly higher increase in probing depth between months 3 and 12 , and more bleeding on probing . The present results confirm the findings of our previous short-term study , indicating that a further reduction of the surface roughness , below a certain " threshold R(a ) " ( 0.2 microns ) , has no major impact on the supra- and subgingival microbial composition The purpose of this study was to characterize and compare by scanning electron microscopy ( SEM ) the maturation of supragingival microbial plaque on enamel and smooth titanium and that of subgingival plaque on cementum , plasma-sprayed titanium and hydroxyapatite surfaces . Specimens ( 6.5 x 2 x 1 mm ) were obtained from titanium implants with smooth transmucosal collars and plasma-sprayed endosseous posts of titanium or hydroxyapatite . Unerupted third molars were sectioned to similar dimensions that included equal lengths of enamel and root surface . Ten patients with post-treatment pocket depths of > 6 mm on 3 non-adjacent teeth were selected and each had 1 set of the 3 specimen types bonded by r and om assignment to the selected teeth . Specimens were positioned so that enamel and /or smooth titanium surfaces were supragingival and cementum and titanium or hydroxyapatite plasma-sprayed surfaces were subgingival . Patients were instructed to stop oral hygiene , after which 2 specimen sets were removed at 1 , 3 , 5 , 7 and 10 days . Two specimens of each type were examined by SEM at each time interval for supra- and subgingival plaque . The sequence of appearance of various microbial morphotypes in supra- and subgingival plaque was similar regardless of surface . In both supra- and subgingival plaque , depending on time interval , cocci , rods of various lengths , filamentous organisms , fusiforms , spirochetes and corn-cob formations were observed . Mineralized plaque was noted on most subgingival specimens by day 10 . These observations indicate that surface of natural teeth , smooth titanium and plasma-sprayed titanium and hydroxyapatite support the maturation of microbial plaque with the successive inclusion of a variety of morphotypes OBJECTIVE To study the influence of perfluoroalkylsiloxane ( PA ) surface modification of silicone rubber voice prostheses on biofouling . DESIGN Placebo-controlled clinical trial . SETTING Tertiary referral center , with specialization in head and neck cancer treatment . PATIENTS Eighteen consecutive patients with laryngectomies and experienced in the use of a voice prosthesis who visited the outpatient clinic for prosthesis replacement . MATERIAL Eighteen partially surface-modified voice prostheses ( 3 with short-chain PAs [ 1 fluorocarbon unit ] and 15 with long-chain PAs [ 8 fluorocarbon units ] ) were inserted via the patients ' tracheoesophageal shunts and remained in place for 2 to 8 weeks . INTERVENTION Replacement of the prostheses . MAIN OUTCOME MEASURES Evaluation of biofilm formation on short- and long-chain PA-modified and original silicone rubber surfaces on the esophageal side of the voice prosthesis . RESULTS The planimetrical biofilm scores of the surfaces of all 3 short-chain PA-treated voice prostheses indicated more biofouling on the treated surfaces than on the untreated surfaces of the same prostheses . For the long-chain PA-treated prostheses , the planimetrical biofilm scores , as well as the numbers of colony-forming units per cm(-2 ) for bacteria and yeasts , indicated less biofouling on the treated side than on the control side for 9 of the 13 prostheses that could be analyzed ( 2 were lost to analysis ) . Identical fungal strains , mainly C and ida sp , were isolated from biofilms on each side of the esophageal flange . CONCLUSIONS Chemisorption of long-chain PAs by the silicone rubber used for voice prostheses reduces biofilm formation in vivo and therefore can be expected to prolong the life of these prostheses . Chemisorption of short-chain PAs by silicone rubber seems to have an adverse effect In the present study , two different fibre-reinforced composites ( FRCs ) ( glass and polyethylene FRC ) , dental ceramic and restorative composite were compared with respect to early plaque formation in vivo . Disc-shaped specimens were r and omly distributed among the upper first and second molars of 14 healthy adult volunteers . Plaque sample s were collected 24 h after the attachment of the specimens . Mutans streptococci ( MS ) , non-mutans streptococci and total facultative bacteria were cultured . The plaque recovered from polyethylene FRC harboured significantly more MS than the plaque of ceramic , restorative composite and glass FRC . For the counts of non-mutans streptococci and total facultative bacteria , polyethylene FRC showed the highest counts , and ceramic showed a trend towards lower counts . The amount of plaque accumulation showed an association to the earlier reported surface roughness values of the studied material s. It was concluded that in the oral environment , polyethylene FRC promotes plaque accumulation and adhesion of MS more than glass FRC , restorative composite and dental ceramic . Glass FRC resembles restorative composite with respect to plaque accumulation and the adherence of MS The purpose of this study was to examine the change in plaque area over nine days in vivo on four material s with different surface free-energies ( s.f.e . ) . Twelve healthy dental students participated in a crossover , split-mouth , double-blind study . Supragingival plaque formation was recorded over a nine-day period , on four different material s : fluorethylenepropylene ( Teflon ) ( FEP ) , parafilm ( PAR ) , cellulose acetate ( CA ) , and enamel ( E ) with s.fe . of 20 , 26 , 57 , and 88 erg/cm2 , respectively . Strips made from the first three material s were stuck to the buccal surface of an upper incisor . The remaining incisor was carefully polished and served as an enamel surface . The increase in plaque was evaluated after three , six , and nine days . A planimetrical analysis was used so that the plaque area could be expressed as a percentage of the total buccal tooth surface . This procedure was repeated on each subject , so that at the end , each pair of central or lateral incisors received the four tested material s. The results indicated that the adherence of micro-organisms on pellicle-coated substrata was influenced by the material 's s.f.e . ; there was an association between the s.f.e . of the substrata and the supragingival plaque extension in vivo . High surface free-energy substrata in the oral cavity attracted more micro-organisms than did low energetic material s. Additionally , the bacterial adhesion seemed very weak on surfaces with a low s.f.e Previous in vivo studies suggested that a high substratum surface free energy ( s.f.e . ) and an increased surface roughness facilitate the supragingival plaque accumulation . It is the aim of this clinical trial to explore the " relative " effect of a combination of these surface characteristics on plaque growth . 2 strips , one made of fluorethylenepropylene ( FEP ) and the other made of cellulose acetate ( CA ) ( polymers with surface free energies of 20 and 58 erg/cm2 , respectively ) were stuck to the labial surface of the central incisors of 16 volunteers . Half the surface of each strip was smooth ( Ra + /- 0.1 microns ) and the other half was rough ( Ra + /- 2.2 microns ) . The undisturbed plaque formation on these strips was followed over a period of 6 days . The plaque extension at day 3 and 6 was scored planimetrically from color slides . Finally , of 6 subjects sample s were taken from the strips as well as from a neighbouring smooth tooth surface ( s.f.e . 88 erg/cm2 ; Ra + /- 0.14 microns ) . These sample s were analysed with a light microscope to score the proportion of coccoid cells , and small , medium , and large rods or fusiform bacteria . At day 3 , a significant difference in plaque accumulation was only obtained when a rough surface was compared with a smooth surface . However , at day 6 , significantly less plaque was recorded on FEP smooth ( 19.4 % ) when compared with CA smooth ( 39.5 % ) . Between FEP rough ( 96.8 % ) and CA rough ( 98.2 % ) , no significant difference appeared . ( ABSTRACT TRUNCATED AT 250 WORDS |
12,899 | 22,681,913 | RESULTS Two consistent positive predictors of symptom change were identified : pre-treatment symptom severity and patient-rated therapeutic alliance .
Contrary to theories predicting increasing immutability with age , there was no evidence that age predicted poorer outcome .
CONCLUSION More severely ill patients may have greater potential to achieve change during therapy , and should remain a focus for psychotherapy services .
The therapeutic alliance is an important common factor predicting outcome in patients with BPD , even in highly disorder-specific treatments .
Outcomes may be improved by further clinical and research focus on forming strong therapeutic alliances . | BACKGROUND There is substantial variation between individuals with borderline personality disorder ( BPD ) in the degree of benefit gained from psychotherapy .
Information on factors predicting the outcome of therapy for this group could facilitate identification of those at risk for poor outcome , and could enable helpful therapy processes to be identified . | Objective : The aim of this study is to compare the clinical outcome of patients with borderline personality disorder ( BPD ) who had received outpatient psychotherapy for 1 year with BPD patients who received no formal psychotherapy for the same period . Method : Thirty patients with BPD were treated by trainee psychotherapists working according to clearly described therapeutic principles . They received intensive audiotaped supervision . Patients were seen twice weekly for 1 year . They were compared with 30 patients subsequently referred to the clinic , for whom no therapist was available and who remained on a waiting list for 1 year , receiving their usual treatment . The outcome measure was a score derived from DSM criteria . It was taken at the beginning and end of the year 's treatment , in the former case , and after at least 1 year on the waiting list in the latter . ( The average waiting period was 17.1 months . ) Results and Conclusions : Patients who received psychotherapy were significantly improved in terms of the DSM score . Thirty percent of treated patients no longer fulfilled DSM-III criteria for BPD . The untreated patients were unchanged This study investigated the quality and development of the therapeutic alliance as a mediator of change in schema-focused therapy ( SFT ) and transference-focused psychotherapy ( TFP ) for borderline personality disorder . Seventy-eight patients were r and omly allocated to 3 years of biweekly SFT or TFP . Scores of both therapists and patients for the therapeutic alliance were higher in SFT than in TFP . Negative ratings of therapists and patients at early treatment were predictive of dropout , whereas increasingly positive ratings of patients in the 1st half of treatment predicted subsequent clinical improvement . Dissimilarity between therapist and patients in pathological personality characteristics had a direct effect on growth of the therapeutic alliance but showed no relationship with clinical improvement . The authors conclude that the therapeutic alliance and specific techniques interact with and influence one another and may serve to facilitate change processes underlying clinical improvement in patients with borderline personality disorder A central component of Dialectical Behavior Therapy ( DBT ) is the teaching of specific behavioral skills with the aim of helping individuals with Borderline Personality Disorder ( BPD ) replace maladaptive behaviors with skillful behavior . Although existing evidence indirectly supports this proposed mechanism of action , no study to date has directly tested it . Therefore , we examined the skills use of 108 women with BPD participating in one of three r and omized control trials throughout one year of treatment and four months of follow-up . Using a hierarchical linear modeling approach we found that although all participants reported using some DBT skills before treatment started , participants treated with DBT reported using three times more skills at the end of treatment than participants treated with a control treatment . Significant mediation effects also indicated that DBT skills use fully mediated the decrease in suicide attempts and depression and the increase in control of anger over time . DBT skills use also partially mediated the decrease of nonsuicidal self-injury over time . Anger suppression and expression were not mediated . This study is the first to clearly support the skills deficit model for BPD by indicating that increasing skills use is a mechanism of change for suicidal behavior , depression , and anger control The primary aim of this study was to examine the prospect i ve association of shame with self-inflicted injury ( SII ) , including suicide attempts and nonsuicidal self-injury , among women with borderline personality disorder ( BPD ) who were enrolled in a clinical trial ( N = 77 ) . A multi- method approach was used to assess self-reported shame , nonverbal shame behaviors , and assessor ratings of shame during an interview regarding antecedents for a recent episode of SII . Higher levels of nonverbal shame behaviors predicted a higher likelihood of subsequent SII , and shorter time to SII , after controlling for past SII as well as other emotions associated with SII . Self-reported state shame and assessor ratings of shame were associated with prospect i ve SII , but not after controlling for other emotions . These findings underscore the important role of shame in SII , particularly shame in the presence of context ual prompts for events that surround episodes of SII Most patients with borderline personality disorder receive no formal treatment for their personality disorder and psychotherapy is widely believed to be necessarily intensive , of long duration and of uncertain effect . This study seeks to demonstrate the scope and limits of time-limited outpatient cognitive analytic psychotherapy . Cases were identified by st and ard diagnostic procedures . Most were referred from psychiatrists and were typical of inner city patient population s. At an assessment 6 months after therapy the 27 patients completing therapy were divided into ' improved ' and ' unimproved ' groups . The patients classified as improved no longer met diagnostic criteria for borderline personality disorder . The two-thirds still traceable were re-tested at 18 months . These groups were compared in terms of a number of pre-therapy measures and features . Poorer outcome was associated with greater severity of borderline features , a history of self-cutting , alcohol abuse and unemployment Although a number of psychotherapeutic modalities for borderline personality disorder ( BPD ) have empirical support , it is unclear what aspects of treatment are responsible for improvement . The present study analyzes the relationships between different techniques and outcomes in a r and omized controlled trial of dynamic deconstructive psychotherapy ( DDP ) for comorbid BPD and alcohol-use disorders . Video recordings of psychotherapy sessions at 3-month intervals were rated to measure therapeutic alliance and the relative frequencies of specific treatment interventions . Outcomes included measures of borderline symptoms , depression , dissociation , social support , alcohol misuse , parasuicide , and institutional care . Discrete sets of techniques were associated with reliable changes in specific outcomes , indicating that treatments for BPD should be tailored to the specific constellation of symptoms presenting in a given individual . The study findings suggest that treatments with a specified set of techniques , such as DDP , dialectical behavior therapy , mentalization-based treatment , schema therapy , supportive therapies , and transference-focused psychotherapy , may be helpful for different individuals , depending on their particular set of symptoms BACKGROUND Longer-term follow-up of patients with borderline personality disorder have found favourable clinical outcomes , with long-term reduction in symptoms and diagnosis . AIMS We examined the 6-year outcome of patients with borderline personality disorder who were r and omised to 1 year of cognitive-behavioural therapy for personality disorders ( CBT-PD ) or treatment as usual ( TAU ) in the BOSCOT trial , in three centres across the UK ( trial registration : IS RCT N86177428 ) . METHOD In total , 106 participants met criteria for borderline personality disorder in the original trial . Patients were interviewed at follow-up by research assistants masked to the patient 's original treatment group , CBT-PD or TAU , using the same measures as in the original r and omised trial . Statistical analyses of data for the group as a whole are based on generalised linear models with repeated measures analysis of variance type models to examine group differences . RESULTS Follow-up data were obtained for 82 % of patients at 6 years . Over half the patients meeting criteria for borderline personality disorder at entry into the study no longer did so 6 years later . The gains of CBT-PD over TAU in reduction of suicidal behaviour seen after 1-year follow-up were maintained . Length of hospitalisation and cost of services were lower in the CBT-PD group compared with the TAU group . CONCLUSIONS Although the use of CBT-PD did not demonstrate a statistically significant cost-effective advantage , the findings indicate the potential for continued long-term cost-offsets that accrue following the initial provision of 1 year of CBT-PD . However , the quality of life and affective disturbance remained poor Changes in attachment organization and reflective function ( RF ) were assessed as putative mechanisms of change in 1 of 3 year-long psychotherapy treatments for patients with borderline personality disorder ( BPD ) . Ninety patients reliably diagnosed with BPD were r and omized to transference-focused psychotherapy ( TFP ) , dialectical behavior therapy , or a modified psychodynamic supportive psychotherapy . Attachment organization was assessed with the Adult Attachment Interview and the RF coding scale . After 12 months of treatment , participants showed a significant increase in the number classified secure with respect to attachment state of mind for TFP but not for the other 2 treatments . Significant changes in narrative coherence and RF were found as a function of treatment , with TFP showing increases in both constructs during treatment . No changes in resolution of loss or trauma were observed across treatments . Findings suggest that 1 year of intensive TFP can increase patients ' narrative coherence and RF . Future research should establish the relationship between these 2 constructs and relevant psychopathology , identify treatment components responsible for effecting these changes , and examine the long-term outcome of these changes A r and omized clinical trial was conducted to evaluate whether Dialectical Behavior Therapy ( DBT ) , an effective cognitive-behavioral treatment for suicidal individuals with borderline personality disorder ( BPD ) , would also be effective for drug-dependent women with BPD when compared with treatment-as-usual ( TAU ) in the community . Subjects were r and omly assigned to either DBT or TAU for a year of treatment . Subjects were assessed at 4 , 8 , and 12 months , and at a 16-month follow-up . Subjects assigned to DBT had significantly greater reductions in drug abuse measured both by structured interviews and urinalyses throughout the treatment year and at follow-up than did subjects assigned to TAU . DBT also maintained subjects in treatment better than did TAU , and subjects assigned to DBT had significantly greater gains in global and social adjustment at follow-up than did those assigned to TAU . DBT has been shown to be more effective than treatment-as-usual in treating drug abuse in this study , providing more support for DBT as an effective treatment for severely dysfunctional BPD patients across a range of presenting problems BACKGROUND AND SIGNIFICANCE The treatment of personality disorders in older adults , particularly those co-morbid with other Axis I disorders ( e.g. , Major Depressive Disorder ) , is an understudied clinical phenomenon . It has also been demonstrated that personality disorders in older adults complicate treatment of other psychopathology , as well as result in heightened interpersonal disturbance and emotional distress . METHODS Two studies utilizing st and ard Dialectical Behavior Therapy ( DBT ) to treat depression and personality disorders in older adults are review ed . Study 1 examined 34 chronically depressed individuals aged 60 and older who were r and omly assigned to receive 28 weeks of antidepressant medication plus clinical management , either alone ( MED ) or with the addition of DBT skills-training and scheduled telephone coaching sessions ( MED + DBT ) . Study 2 had two phases of treatment : Phase I : 8-week open-trial of antidepressant medication ( n = 65 ) ; Phase II : 24-week r and omized trial of DBT + MED versus MED alone for those who prospect ively failed to respond to the Phase I medication trial ( n = 37 ) . RESULTS Study 1 demonstrated that 71 % of MED + DBT patients were in remission at post-treatment , in contrast to 47 % of MED patients . This became a significant difference at the 6-month follow-up ; where 75 % of MED + DBT-D patients were in remission compared with only 31 % of MED patients . Study 2 showed that after 8 weeks of treatment with antidepressant medication alone ( Phase 1 ) only 14 % of the sample had at least a 50 % reduction in HAM-D scores . Phase II results showed on average , the DBT + MED group reached depression remission by the post-group assessment and maintained these gains while the MED group did not reach remission , until the follow-up assessment . Results demonstrated superiority of DBT + MED compared to MED alone on Interpersonal Sensitivity and Interpersonal Aggression at post-treatment and 6-month follow-up . CONCLUSION Results from these two treatment development studies indicate that applying st and ard DBT for the treatment of co-morbid MDD or MDD + PD in older adults is feasible , acceptable , and has clinical promise . Modifications to st and ard DBT and an overview of a new treatment manual for this population are summarized Background : A primary goal of dialectical behaviour therapy ( DBT ) is to reduce self-harm , but findings from empirical studies are inconclusive . The aim of this study was to assess the effectiveness and cost-effectiveness of DBT in reducing self-harm in patients with personality disorder . Methods : Participants with a personality disorder and at least 5 days of self-harm in the previous year were r and omised to receive 12 months of either DBT or treatment as usual ( TAU ) . The primary outcome was the frequency of days with self-harm ; secondary outcomes included borderline personality disorder symptoms , general psychiatric symptoms , subjective quality of life , and costs of care . Results : Forty patients each were r and omised to DBT and TAU . In an intention-to-treat analysis , there was a statistically significant treatment by time interaction for self-harm ( incidence rate ratio 0.91 , 95 % CI 0.89–0.92 , p < 0.001 ) . For every 2 months spent in DBT , the risk of self-harm decreased by 9 % relative to TAU . There was no evidence of differences on any secondary outcomes . The economic analysis revealed a total cost of a mean of 5,685 GBP ( 6,786 EUR ) in DBT compared to a mean of 3,754 GBP ( 4,481 EUR ) in TAU , but the difference was not significant ( 95 % CI –603 to 4,599 GBP ) . Forty-eight per cent of patients completed DBT . They had a greater reduction in self-harm compared to dropouts ( incidence rate ratio 0.78 , 95 % CI 0.76–0.80 , p < 0.001 ) . Conclusions : DBT can be effective in reducing self-harm in patients with personality disorder , possibly incurring higher total treatment costs . The effect is stronger in those who complete treatment . Future research should explore how to improve treatment adherence This study examined the association of novelty seeking , harm avoidance , and reward dependence with different types ( suicide attempts vs. nonsuicidal self-injury ) and aspects ( medical risk , impulsiveness , suicide intent ) of self-injury over a 12-month period . Fifty-five female patients with borderline personality disorder enrolled in clinical trials completed Cloninger 's Temperament and Character Inventory at pretreatment as well as the Suicide Attempt Self-Injury Interview at four-month intervals starting from the pretreatment assessment . Regression analyses indicated that the reward dependence subscale of attachment , a protective factor , was most consistently and uniquely associated with aspects of self-injury , including pre study and prospect i ve nonsuicidal self-injury and suicide intent , and prospect i ve suicide attempts . After controlling for pre study self-injury , few temperament variables predicted prospect i ve self-injury . Higher scores on both the novelty seeking subscale of impulsiveness and the reward dependence attachment subscale were associated with lower prospect i ve suicide intent even after controlling for pre- study suicide intent Surprisingly few studies have investigated the accuracy of prognostic assessment s of therapy outcome by clinicians . The objective of the present study was to investigate the relationship between clinicians ' prognostic assessment s and patient characteristics and treatment outcome . Seventy-one patients with a borderline personality disorder r and omly allocated to schema-focused therapy ( SFT ) or transference-focused psychotherapy ( TFP ) were assessed every 3 months for 3 years . Prognostic assessment s proved to be unrelated to patients ' biographical ( i.e. , age , gender , education level , and employment level ) and clinical characteristics ( i.e. , number of Axis I and Axis II diagnoses , and severity of psychiatric symptoms or borderline personality pathology ) . Clinical assessors as well as therapists rated the probability of success for SFT to be higher than for TFP . Prospect i ve assessment s of assessors and therapists accurately predicted different indices of outcome above and independent of patient characteristics . The prediction of outcome in the TFP condition in particular proved to be valid . Identifying prognostic markers of treatment outcome as used by clinicians in their prognostic assessment s may improve current prediction models and patient-treatment matching OBJECTIVE This study compared the effectiveness of psychoanalytically oriented partial hospitalization with st and ard psychiatric care for patients with borderline personality disorder . METHOD Thirty-eight patients with borderline personality disorder , diagnosed according to st and ardized criteria , were allocated either to a partially hospitalized group or to a st and ard psychiatric care ( control ) group in a r and omized controlled design . Treatment , which included individual and group psychoanalytic psychotherapy , was for a maximum of 18 months . Outcome measures included the frequency of suicide attempts and acts of self-harm , the number and duration of inpatient admissions , the use of psychotropic medication , and self-report measures of depression , anxiety , general symptom distress , interpersonal function , and social adjustment . Data analysis used repeated measures analysis of covariance and nonparametric tests of trend . RESULTS Patients who were partially hospitalized showed a statistically significant decrease on all measures in contrast to the control group , which showed limited change or deterioration over the same period . An improvement in depressive symptoms , a decrease in suicidal and self-mutilatory acts , reduced inpatient days , and better social and interpersonal function began at 6 months and continued until the end of treatment at 18 months . CONCLUSIONS Psychoanalytically oriented partial hospitalization is superior to st and ard psychiatric care for patients with borderline personality disorder . Replication is needed with larger groups , but these results suggest that partial hospitalization may offer an alternative to inpatient treatment A substantial proportion of Borderline Personality Disorder ( BPD ) patients respond by a marked decrease of psychopathology when treated with Dialectical Behavioral Therapy ( DBT ) . To further enhance the rate of DBT-response , it is useful to identify characteristics related to unsatisfactory response . As DBT relies on emotional learning , we explored whether dissociation-which is known to interfere with learning- predicts poor response to DBT . Fifty-seven Borderline Personality Disorder ( BPD ) patients ( DSM-IV ) were prospect ively observed during a three-month inpatient DBT program . Pre-post improvements in general psychopathology ( SCL-90-R ) were predicted from baseline scores of the Dissociative Experiences Scale ( DES ) by regression models accounting for baseline psychopathology . High DES-scores were related to poor pre-post improvement ( β = -0.017 ± 0.006 , p = 0.008 ) . The data yielded no evidence that some facets of dissociation are more important in predicting DBT-response than others . The results suggest that dissociation in borderline- patients should be closely monitored and targeted during DBT . At this stage , research on treatment of dissociation ( e.g. , specific skills training ) is warranted Dialectical Behavioral Therapy ( DBT ) was initially developed and evaluated as an outpatient treatment program for chronically suicidal individuals meeting criteria for borderline personality disorder ( BPD ) . Within the last few years , several adaptations to specific setting s have been developed . This study aims to evaluate a three-month DBT inpatient treatment program . Clinical outcomes , including changes on measures of psychopathology and frequency of self-mutilating acts , were assessed for 50 female patients meeting criteria for BPD . Thirty-one patients had participated in a DBT inpatient program , and 19 patients had been placed on a waiting list and received treatment as usual in the community . Post-testing was conducted four months after the initial assessment ( i.e. four weeks after discharge for the DBT group ) . Pre-post-comparison showed significant changes for the DBT group on 10 of 11 psychopathological variables and significant reductions in self-injurious behavior . The waiting list group did not show any significant changes at the four-months point . The DBT group improved significantly more than participants on the waiting list on seven of the nine variables analyzed , including depression , anxiety , interpersonal functioning , social adjustment , global psychopathology and self-mutilation . Analyses based on Jacobson 's criteria for clinical ly relevant change indicated that 42 % of those receiving DBT had clinical ly recovered on a general measure of psychopathology . The data suggest that three months of inpatient DBT treatment is significantly superior to non-specific outpatient treatment . Within a relatively short time frame , improvement was found across a broad range of psychopathological features . Stability of the recovery after one month following discharge , however , was not evaluated and requires further study A r and omized clinical trial was conducted to evaluate the effectiveness of a cognitive-behavioral therapy , ie , dialectical behavior therapy , for the treatment of chronically parasuicidal women who met criteria for borderline personality disorder . The treatment lasted 1 year , with assessment every 4 months . The control condition was " treatment as usual " in the community . At most assessment points and during the entire year , the subjects who received dialectical behavior therapy had fewer incidences of parasuicide and less medically severe parasuicides , were more likely to stay in individual therapy , and had fewer inpatient psychiatric days . There were no between-group differences on measures of depression , hopelessness , suicide ideation , or reasons for living although scores on all four measures decreased throughout the year CONTEXT Dialectical behavior therapy ( DBT ) is a treatment for suicidal behavior and borderline personality disorder with well-documented efficacy . OBJECTIVE To evaluate the hypothesis that unique aspects of DBT are more efficacious compared with treatment offered by non-behavioral psychotherapy experts . DESIGN One-year r and omized controlled trial , plus 1 year of posttreatment follow-up . SETTING University outpatient clinic and community practice . PARTICIPANTS One hundred one clinical ly referred women with recent suicidal and self-injurious behaviors meeting DSM-IV criteria , matched to condition on age , suicide attempt history , negative prognostic indication , and number of lifetime intentional self-injuries and psychiatric hospitalizations . INTERVENTION One year of DBT or 1 year of community treatment by experts ( developed to maximize internal validity by controlling for therapist sex , availability , expertise , allegiance , training and experience , consultation availability , and institutional prestige ) . MAIN OUTCOME MEASURES Trimester assessment s of suicidal behaviors , emergency services use , and general psychological functioning . Measures were selected based on previous outcome studies of DBT . Outcome variables were evaluated by blinded assessors . RESULTS Dialectical behavior therapy was associated with better outcomes in the intent-to-treat analysis than community treatment by experts in most target areas during the 2-year treatment and follow-up period . Subjects receiving DBT were half as likely to make a suicide attempt ( hazard ratio , 2.66 ; P = .005 ) , required less hospitalization for suicide ideation ( F(1,92 ) = 7.3 ; P = .004 ) , and had lower medical risk ( F(1,50 ) = 3.2 ; P = .04 ) across all suicide attempts and self-injurious acts combined . Subjects receiving DBT were less likely to drop out of treatment ( hazard ratio , 3.2 ; P < .001 ) and had fewer psychiatric hospitalizations ( F(1,92 ) = 6.0 ; P = .007 ) and psychiatric emergency department visits ( F(1,92 ) = 2.9 ; P = .04 ) . CONCLUSIONS Our findings replicate those of previous studies of DBT and suggest that the effectiveness of DBT can not reasonably be attributed to general factors associated with expert psychotherapy . Dialectical behavior therapy appears to be uniquely effective in reducing suicide attempts R and omised controlled studies in research environments have demonstrated dialectical behaviour therapy ( DBT ) to be more efficacious than treatment as usual in reducing suicidal behaviour in patients with borderline personality disorder ( BPD ) . Limited evidence exists for the effectiveness of DBT in the treatment of BPD within routine clinical setting s. This study examines the clinical and cost effectiveness of providing DBT over treatment as usual in a routine Australian public mental health service . Forty-three adult patients with BPD were provided with outpatient DBT for six months with patient outcomes compared to those obtained from patients in a wait list group receiving treatment as usual ( TAU ) from the same service . After six months of treatment the DBT group showed significantly greater reductions in suicidal/non-suicidal self-injury , emergency department visits , psychiatric admissions and bed days . Self-report measures were administered to a reduced sample of patients . With this group , DBT patients demonstrated significantly improved depression , anxiety and general symptom severity scores compared to TAU at six months . Average treatment costs were significantly lower for those patients in DBT than those receiving TAU . Therapists who received intensive DBT training were shown to produce significantly greater improvements in patients ' suicidal and non-suicidal self-injury than therapists who received only 4 day basic training . Further clinical improvements were achieved in patients offered an additional six months of DBT . This study demonstrates that providing DBT to patients within routine public mental health setting s can be both clinical ly effective and cost effective OBJECTIVE This r and omized controlled trial tested the effectiveness of an 18-month mentalization-based treatment ( MBT ) approach in an outpatient context against a structured clinical management ( SCM ) outpatient approach for treatment of borderline personality disorder . METHOD Patients ( N=134 ) consecutively referred to a specialist personality disorder treatment center and meeting selection criteria were r and omly allocated to MBT or SCM . Eleven mental health professionals equal in years of experience and training served as therapists . Independent evaluators blind to treatment allocation conducted assessment s every 6 months . The primary outcome was the occurrence of crisis events , a composite of suicidal and severe self-injurious behaviors and hospitalization . Secondary outcomes included social and interpersonal functioning and self-reported symptoms . Outcome measures , assessed at 6-month intervals , were analyzed using mixed effects logistic regressions for binary data , Poisson regression models for count data , and mixed effects linear growth curve models for self-report variables . RESULTS Substantial improvements were observed in both conditions across all outcome variables . Patients r and omly assigned to MBT showed a steeper decline of both self-reported and clinical ly significant problems , including suicide attempts and hospitalization . CONCLUSIONS Structured treatments improve outcomes for individuals with borderline personality disorder . A focus on specific psychological processes brings additional benefits to structured clinical support . Mentalization-based treatment is relatively undem and ing in terms of training so it may be useful for implementation into general mental health services . Further evaluations by independent research groups are now required We assessed the effect of DBT skills utilization on features of borderline personality disorder as measured by the Personality Assessment Inventory-Borderline Features Scale ( PAI-BOR ) . Participants were out patients ( N = 27 ) enrolled in a dialectical behavior therapy ( DBT ) program in a university-affiliated community mental health clinic . Diary cards were collected each week to track self-reported skills use . At the beginning of each new skills training module , patients completed another PAI-BOR . Univariate and multilevel analyses indicated significant improvement on the total PAI-BOR score and on several PAI-BOR subscale scores . Results also revealed that overall DBT skills use increased significantly over time , as did individual skills related to mindfulness , interpersonal effectiveness , emotion regulation , and distress tolerance . Multilevel modeling results indicated that overall skills use showed a significant effect on PAI-BOR total scores , Affective Instability scores , Identity Problems scores , and Negative Relationships scores , even after controlling for initial levels of distress and diary card compliance OBJECTIVE Systems Training for Emotional Predictability and Problem Solving ( STEPPS ) is a 20-week manual-based group treatment program for out patients with borderline personality disorder that combines cognitive behavioral elements and skills training with a systems component . The authors compared STEPPS plus treatment as usual with treatment as usual alone in a r and omized controlled trial . METHOD Subjects with borderline personality disorder were r and omly assigned to STEPPS plus treatment as usual or treatment as usual alone . Total score on the Zanarini Rating Scale for Borderline Personality Disorder was the primary outcome measure . Secondary outcomes included measures of global functioning , depression , impulsivity , and social functioning ; suicide attempts and self-harm acts ; and crisis utilization . Subjects were followed 1 year posttreatment . A linear mixed-effects model was used in the analysis . RESULTS Data pertaining to 124 subjects ( STEPPS plus treatment as usual [ N=65 ] ; treatment as usual alone [ N=59 ] ) were analyzed . Subjects assigned to STEPPS plus treatment as usual experienced greater improvement in the Zanarini Rating Scale for Borderline Personality Disorder total score and subscales assessing affective , cognitive , interpersonal , and impulsive domains . STEPPS plus treatment as usual also led to greater improvements in impulsivity , negative affectivity , mood , and global functioning . These differences yielded moderate to large effect sizes . There were no differences between groups for suicide attempts , self-harm acts , or hospitalizations . Most gains attributed to STEPPS were maintained during follow-up . Fewer STEPPS plus treatment as usual subjects had emergency department visits during treatment and follow-up . The discontinuation rate was high in both groups . CONCLUSIONS STEPPS , an adjunctive group treatment , can deliver clinical ly meaningful improvements in borderline personality disorder-related symptoms and behaviors , enhance global functioning , and relieve depression |
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