Rifampicin chemoprophylaxis in preventing leprosy in contacts of patients with leprosy: a comprehensive systematic review protocol Lesional characteristics and histopathology in paucibacillary leprosy patients with 2 or 3 skin lesions: comparison between ROM and PB-MDT regimens. Efficacy of single-dose chemotherapy (rifampicin, ofloxacin and minocycline-ROM) in PB leprosy patients with 2 to 5 skin lesions, India: randomised double-blind trial. Room for improvement? A survey of the methods used in systematic reviews of adverse effects Photodynamic therapy for acne vulgaris: a randomized, controlled, split-face clinical trial of topical aminolevulinic acid and pulsed dye laser therapy. Can you believe what you read in the papers? Uniform multidrug therapy for leprosy patients in Brazil (U-MDT/CT-BR): Results of an open label, randomized and controlled clinical trial, among multibacillary patients How useful are systematic reviews for informing palliative care practice? Survey of 25 Cochrane systematic reviews An educational intervention to improve diagnosis and management of suspicious skin lesions Hyperpigmented dermal macules in children following the administration of Maloprim for malaria chemoprophylaxis. Key Steps in Conducting Systematic Reviews for Underpinning Clinical Practice Guidelines: Methodology of the European Association of Urology. High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial. Spinal cord MRI in clinically isolated optic neuritis The methodological quality of randomized controlled trials of homeopathy, herbal medicines and acupuncture. Improving the quality of randomized controlled trials in Chinese herbal medicine, part I: clinical trial design and methodology. A Systematic Evaluation of the Impact of STRICTA and CONSORT Recommendations on Quality of Reporting for Acupuncture Trials Feasibility and psychometrics of an ambulatory hot flash monitoring device. Effect of a web-based curriculum on primary care practice: basic skin cancer triage trial. Clinical effectiveness of manual therapy for the management of musculoskeletal and non-musculoskeletal conditions: systematic review and update of UK evidence report Use of Vital Pulp Therapies in Primary Teeth with Deep Caries Lesions. Examining the use of process evaluations of randomised controlled trials of complex interventions addressing chronic disease in primary health care—a systematic review protocol The National Eye Institute Visual Function Questionnaire: experience of the ONTT. Optic Neuritis Treatment Trial. A checklist to evaluate a report of a nonpharmacological trial (CLEAR NPT) was developed using consensus.
Review question / objective What is the effectiveness of rifampicin chemoprophylaxis in preventing leprosy in contacts of patients with leprosy ? What are the experiences and acceptability with the use of rifampin chemoprophylaxis in the prevention of disease from contacts with patients who have leprosy , in patients with leprosy following treatment and in family and health care professionals ? Background Leprosy is globally acknowledged as a millenary and stigmatizing disease and a condition with attributed consequences such as physical deformities and disabilities . From a multi‐causal perspective , there is evidence that leprosy occurs more often in men than in women , is distributed across all age groups and occurs mainly among people living in unfavorable socioeconomic circumstances , who are also the most affected by public segregation policies . 1–4 In 2013 , a total of 215,656 new cases of leprosy were detected worldwide . Regions with the highest number of cases are Southeast Asia ( 72.1 % ) the Americas ( 15.3 % ) . Whereas the countries with the highest prevalence were India ( 58.8 % ) and Brazil ( 14.4 % ) . 5 Hansen 's bacillus ( Mycobacterium leprae ) is considered a microorganism of high infectivity and low pathogenicity and virulence . It is transmitted via nasal oropharyngeal secretions and breaks in the skin of infected patients . Therefore , the main form of transmissibility is inter‐human and the greatest risk of contagion is cohabitation with these patients .1–3 It is estimated that most individuals have a natural resistance to Mycobacterium leprae ( M. leprae ) and that some are prone to developing a severe form of the disease , the multibacillary forms . Studies on exogenous reinfection and endogenous reactivation in chronic diseases , such as tuberculosis and leprosy , show that susceptible individuals become infected by the bacillus through contact with multibacillary patients .1–3,6,7 The surveillance of leprosy contacts is a priority action for control of the disease . Children are exposed to the highest risk of becoming infected by being in contact with a family member or anyone close to them who has the disease . Having a current case of leprosy in the family is associated with a 2.9 times greater risk of a healthy family member becoming infected , and that risk increases when the family has a history of the disease.3,6–9 Bakker et al.7 reported that household contacts of multibacillary patients presented a four times greater risk of becoming infected with the disease compared to non‐contacts . For Ximenes et al.,10 the condition of being a contact of individuals with leprosy represented twice the risk of retreatment due to recurrence in relation to the control group . Therefore , alternative or complementary strategies , such as chemoprophylaxis , must be sought as a form of prevention of the disease . Chemoprophylaxis is defined as the administration of drugs capable of preventing an infection or keeping infected individuals from falling ill . In leprosy , the preventive strategy consists of employing medications to prevent the infection by M. leprae in people with a higher risk of exposure to the disease , i.e. those in contact with the patient . Therefore , chemoprophylaxis plays an important role in the protection of individuals vulnerable to the disease . However , studies regarding its effective utilization are inconclusive.11–15 The first investigations of the utilization of prophylaxis in leprosy contacts in the 1960s and 1970s included dapsone and acedapsone and later in the 1980s and 1990s rifampicin . However , interest in this type of research decreased after 1982 when the World Health Organization ( WHO ) introduced multidrugtherapy ( MDT ) for the treatment of leprosy.16–19 Multidrugtherapy is a combination of three drugs , dapsone , rifampicin and clofazimine , to prevent the selection of resistant strains . As of 1997 , the WHO adopted the alternative rifampicin , ofloxacin and minocycline ( ROM ) regimen , recommended for paucibacillary cases with a single lesion without the involvement of nerve stems.19,20 Adoption of these measures was expected to result in a reduction in the incidence of leprosy as a public health problem ; however , the observed result was not significant in terms of reducing the incidence of newly detected cases . Furthermore , considering the evidence of resistance to monotherapy with dapsone , there was a rise in interest in intervention studies , particularly using rifampicin in household and community contacts.1,2,5,11,12 However , some studies have indicated little or no protection against the disease through the use of rifampicin . While Moet et al.14 and Feenstra et al.21 observed protection of two years in household contacts with a single dose of rifampicin , Bakker et al.13 showed no difference between the experimental group and the control group with two doses of rifampicin , 600 mg for adults and 300 mg for children . Another study of people at high risk of contracting the disease that used a single dose of ROM and rifampicin showed that there was a reduction of type immunoglobulin M antibodies among adults in both interventions .22 Meta‐analyis of dapsone , acepdapsone and rifampicin compared with placebo showed that chemoprophlasys is an effective measure to prevent leprosy . 12 Currently , strategies using a combination of the Bacillus Calmette‐Guérin ( BCG ) and chemoprophylaxis with rifampicin in leprosy contacts appear to be complementary measures for protection against the disease . This strategy showed a protective effect of 80%.23 Studies of acceptability and experience of chemoprophylaxis to control leprosy with individuals and health professionals are scarce . In a qualitative study , Feenstra et al.24 concluded that chemoprophylaxis for household contacts of leprosy patients is an effective and socially acceptable addition to the current leprosy control program . A preliminary search of the Joanna Briggs Data base of Systematic Review s and Implementation Reports , the Cochrane Library , CINAHL , PubMed and PROSPERO has revealed that there are no systematic review s ( either published or underway ) on this topic . In this context , it is un question ably useful to integrate the scientific evidence from studies that evaluated the effectiveness of the rifampicin chemoprophylaxis in leprosy contacts , the experiences and acceptability of contacts of leprosy patients , patients with leprosy following treatment and family and health care professionals about this strategy for the prevention of the disease . This knowledge can support the measures adopted to reduce endemicity , which strengthens the quality of the care delivered to the population most vulnerable to becoming ill . Operational definitions : Leprosy patients : individuals who present one or more of the following cardinal signs and who require multidrugtherapy : lesion(s ) and /or skin areas with altered sensitivity ; affected peripheral nerve(s ) , with or without thickening , associated with sensitive and /or motor and /or autonomic changes ; and a positive skin smear bacilloscopy . Cases are classified as paucibacillary or multibacillary based on the number of lesions and /or bacilloscopy when available ; cases are considered paucibacillary when patients present five or fewer skin lesions and /or negative bacilloscopy , corresponding to the undetermined and tuberculoid clinical forms ; multibacillary cases are when patients present more than five skin lesions and positive bacilloscopy , corresponding to the dimorphous and Virchow 's forms of the disease.1–4,25 Leprosy case : term used in epidemiology to identify individuals with leprosy for purpose s of monitoring the health conditions of a population .2,26 Chemoprophylaxis : the administration of drugs capable of preventing the infection or keeping infected individuals from falling ill.11,12 Contacts : those who cohabit or have cohabited with leprosy patients .12,14,21 Index case : the first case of the disease among several similar cases that are epidemiologically related with the secondary case ( index case contacts).21 Recurrence : the reappearance of signs and symptoms of the disease after recuperation from a first occurrence of the disease , usually within five years.6,10,27 Treatment ab and onment : interrupting treatment for over twelve months.6,10 Therapeutic regimen established for confirmed leprosy cases : for paucibacillary ( PB ) cases , six monthly supervised doses of rifampicin ( RFM ) 450‐600 mg , and daily self‐administered doses of dapsone ( DDS ) 50‐100 mg , for up to nine months ; for multibacillary ( MB ) cases , twelve supervised monthly doses of rifampicin ( RFM ) 450‐600 mg and clofazimine ( CFZ ) 100‐300 mg , associated to daily self‐administered doses of dapsone ( DDS ) 50‐100 mg and CFZ 50 mg , for up to 18 months . An alternative treatment for MB is 24 doses within 36 months.1,2,19 Rifampicin chemoprophylaxis regimens : single‐dose rifampicin of 25 mg/kg or monthly dose for six months ; double‐dose rifampicin or combined regimens of ROM ‐ rifampicin ( 600 mg ) , ofloxacin ( 400 mg ) and minocycline ( 100 mg ) , according to body weight.13–15,21 Efficacy/effectiveness : proof ( or not ) of successful intervention . Efficacy is the result of an intervention performed under ideal , well‐controlled conditions , such as in r and omized clinical trials . Effectiveness refers to the result of an intervention applied under usual medical practice conditions.28 Operational classification : paucibacillary and multibacillary.1,2 , 25 Comorbidities : morbidities possibly associated with leprosy , such as tuberculosis , diabetes , HIV/AIDS , and others.1,2  BCG vaccination scar : result ing from the intradermal injection of Bacillus Calmette‐Guérin ( BCG ) vaccine on the deltoid , used to prevent tuberculosis and leprosy.23,29 Adverse events : negative effects result ing from the actions of drugs.1,2 Incidence rate : measures the frequency or likelihood of new cases of diseases occurring in a population .30 Estimated effect of an intervention : shows the theoretical distribution of possible effects Paucibacillary ( PB ) patients form a large segment of newly diagnosed leprosy patients and those who present with only two or three skin lesions could have problems with compliance . With prolonged anti-leprosy drug regimens that last over six months . ROM therapy , a one-dose regimen , offers an attractive alternative in treating such patients . We conducted a longitudinal study of 51 such PB patients , placing them in two groups at r and om : one receiving the st and ard PB-MDT regimen , and the other the ROM regimen . Patients were followed up for 2 years , with a comprehensive clinical examination done every six months . 14 patients , 7 in each group , also had their skin biopsies evaluated histopathologically at recruitment , at 6 months and at the end of 2 years . There was a consistent improvement of lesions in both the groups over time . The fall in granuloma fraction and the clearance of the initial bacterial index were seen in the histopathology of both groups . Although the PB-MDT regimen is an effective and robust one , the operational convenience and drug compliance with ROM could make it an acceptable , parallel regimen for PB patients when the disease is localized to 2 or 3 skin lesions UNLABELLED We conducted r and omized double-blind trial for single-dose of Rifampicin , Ofloxacin and Minocycline ( ROM ) compared to WHO-PB-MDT among paucibacillary ( PB ) leprosy patients with 2 - 5 skin lesions . We enrolled 1526 patients from five centres ( ROM=762 ; WHO-PB-MDT=764 ) and followed them for 36 months posttreatment during 1998 - 2003 . We generated information on clearance of skin lesions and relapse rates per 100 person-years ( PY ) for all the five centres . At base-line , the patients in the two arms were comparable . Complete clearance of skin lesions was similar ( 72 % vs. 72.1 % ; p=0.95 ) in both the arms . Clinical scores declined steadily and equally . Difference in relapse rates was statistically highly significant ( ROM=1.13 and WHO-PB-MDT=0.35 per 100 PY ; mid-p exact=0.001016 ) . Twenty eight of 38 of these relapses occurred within 18 months . In all , 10 suspected adverse drug reactions were.observed ( ROM=2 ; WHO-PB-MDT=8 ) . We extended the follow-up to 48 months for 1082 of 1526 patients from two programme-based centres . No further relapses occurred . Decline in clinical score was not dependent on age , gender , number of lesions or affected body parts . Single dose ROM , though less effective than the st and ard WHO-PB-MDT regimen conceptually offers an alternative treatment regimen for PB leprosy patients with 2 - 5 lesions only when careful follow-up for relapse is possible . Registered at the Clinical Trials Registry of India ; REGISTRATION NUMBER Background Although the methods for conducting systematic review s of efficacy are well established , there is much less guidance on how systematic review s of adverse effects should be performed . Methods In order to determine where method ological research is most needed to improve systematic review s of adverse effects of health care interventions , we conducted a descriptive analysis of systematic review s published between 1994 and 2005 . We search ed the Data base of Abstract s of Review s of Effects ( DARE ) and The Cochrane Data base of Systematic Review s ( CDSR ) to identify systematic review s in which the primary outcome was an adverse effect or effects . We then extracted data on many of the elements of the systematic review process including : types of interventions studied , adverse effects of interest , re sources search ed , search strategies , data sources included in review s , quality assessment of primary data , nature of the data analysis , and source of funding . Results 256 review s were included in our analysis , of which the majority evaluated drug interventions and pre-specified the adverse effect or effects of interest . A median of 3 re sources were search ed for each review and very few review s ( 13/256 ) provided sufficient information to reproduce their search strategies . Although more than three quarters ( 185/243 ) of the review s sought to include data from sources other than r and omised controlled trials , fewer than half ( 106/256 ) assessed the quality of the studies that were included . Data were pooled quantitatively in most of the review s ( 165/256 ) but heterogeneity was not always considered . Less than half ( 123/256 ) of the review s reported on the source of funding . Conclusion There is an obvious need to improve the methodology and reporting of systematic review s of adverse effects . The methodology around identification and quality assessment of primary data is the main concern BACKGROUND There remains the need for more effective therapeutic options to treat acne vulgaris . Interest in light-based acne treatments has increased , but few r and omized , controlled clinical trials assessing the value of photodynamic therapy ( PDT ) for acne have been reported . AIMS We sought to examine the efficacy of PDT using 5-aminolevulinic acid ( ALA ) and pulsed dye laser therapy in the treatment of acne . PATIENTS / METHODS We conducted a r and omized , controlled , split-face , single-blind clinical trial of 44 patients with facial acne . Patients were r and omized to receive three pulsed dye laser treatments to one side of the face after a 60 - 90 min ALA application time , while the contralateral side remained untreated and served as a control . Serial blinded lesion counts and global acne severity ratings were performed . RESULTS Global acne severity ratings improved bilaterally with the improvement noted to be statistically significantly greater in treated skin than in untreated skin . Erythematous macules ( remnants of previously active inflammatory lesions ) decreased in number in treated skin when compared with control skin and there was a transient but significant decrease in inflammatory papules in treated skin when compared with untreated skin . There were no other statistically significant differences between treated and untreated sides of the face in terms of counts of any subtype of acne lesion . Thirty percent of patients were deemed responders to this treatment with respect to improvement in their inflammatory lesion counts , while only 7 % of patients responded in terms of noninflammatory lesion counts . CONCLUSIONS PDT with the treatment regimen employed here may be beneficial for a subgroup of patients with inflammatory acne The number of reports of clinical trials grows by hundreds every week . However , this does not mean that people making decisions about healthcare are finding it easier to obtain reliable knowledge for these decisions . Some of the information is unreliable . Systematic review s are helping to resolve this by bringing together the research on a topic , appraising and summarising it . But the quality of these review s depends greatly on the quality of the studies , and this usually means the quality of their reports . If there are fundamental flaws within a study , such as the use of inappropriate ' r and omisation ' techniques in the context of review s of the effects of interventions , the review ers will not be able to fix these . Worse still , if they are not aware of underlying flaws , they might make incorrect judgements about the quality of the research in their review . A study by Wu and colleagues of ' r and omised trials ' from China provides a reminder of the cautious approach needed by users of scientific articles . They contacted the authors of more than 2000 research articles , which purported to be reports of r and omised trials ; and concluded that ten of every 11 studies cl aim ing to be a r and omised trial probably did not use r and om allocation . Better education of research ers , peer review ers and editors about what is , and is not , a properly r and omised trial is needed ; along with better reporting of the details for how participants were allocated to the different interventions . Systematic review ers must be cautious in making assumptions about the conduct of trials based on simple phrases about the trial methodology , rather than a full description of the methods actually used . It 's not that you ca n't believe anything that you read in the papers , just that you can not believe everything Background Leprosy control is based on early diagnosis and multidrug therapy . For treatment purpose s , leprosy patients can be classified as paucibacillary ( PB ) or multibacillary ( MB ) , according to the number of skin lesions . Studies regarding a uniform treatment regimen ( U-MDT ) for all leprosy patients have been encouraged by the WHO , rendering disease classification unnecessary . Methodology and findings An independent , r and omized , controlled clinical trial conducted from 2007 to 2015 in Brazil , compared main outcomes ( frequency of reactions , bacilloscopic index trend , disability progression and relapse rates ) among MB patients treated with a uniform regimen/U-MDT ( dapsone+rifampicin+clofazimine for six months )  versus WHO regular-MDT/R-MDT ( dapsone+rifampicin+clofazimine for 12 months ) . A total of 613 newly diagnosed , untreated MB patients with high bacterial load were included . There was no statistically significant difference in Kaplan-Meyer survival function regarding reaction or disability progression among patients in the U-MDT and R-MDT groups , with more than 25 % disability progression in both groups . The full mixed effects model adjusted for the bacilloscopic index average trend in time showed no statistically significant difference for the regression coefficient in both groups and for interaction variables that included treatment group . During active follow up , four patients in U-MDT group relapsed representing a relapse rate of 2.6 per 1000 patients per year of active follow up ( 95 % CI [ 0·81 , 6·2 ] per 1000 ) . During passive follow up three patients relapsed in U-MDT and one in R-MTD . As this period corresponds to passive follow up , sensitivity analysis estimated the relapse rate for the entire follow up period between 2·9- and 4·5 per 1000 people per year . Conclusion Our results on the first r and omized and controlled study on U-MDT together with the results from three previous studies performed in China , India and Bangladesh , support the hypothesis that UMDT is an acceptable option to be adopted in endemic countries to treat leprosy patients in the field worldwide . Trial registration Clinical Trials.gov : Background In contemporary medical research , r and omised controlled trials are seen as the gold st and ard for establishing treatment effects where it is ethical and practical to conduct them . In palliative care such trials are often impractical , unethical , or extremely difficult , with multiple method ological problems . We review the utility of Cochrane review s in informing palliative care practice . Methods Published review s in palliative care registered with the Cochrane Pain , Palliative and Supportive Care Group as of December 2007 were obtained from the Cochrane Data base of Systematic Review s , issue 1 , 2008 . We review ed the quality and quantity of primary studies available for each review , assessed the quality of the review process , and judged the strength of the evidence presented . There was no prior intention to perform any statistical analyses . Results 25 published systematic review s were identified . Numbers of included trials ranged from none to 54 . Within each review , included trials were heterogeneous with respect to patients , interventions , and outcomes , and the number of patients contributing to any single analysis was generally much lower than the total included in the review . A variety of tools were used to assess trial quality ; seven review s did not use this information to exclude low quality studies , weight analyses , or perform sensitivity analysis for effect of low quality . Authors indicated that there were frequently major problems with the primary studies , individually or in aggregate . Our judgment was that the review ing process was generally good in these review s , and that conclusions were limited by the number , size , quality and validity of the primary studies .We judged the evidence about 23 of the 25 interventions to be weak . Two review s had stronger evidence , but with limitations due to method ological heterogeneity or definition of outcomes . No review provided strong evidence of no effect . Conclusion Cochrane review s in palliative care are well performed , but fail to provide good evidence for clinical practice because the primary studies are few in number , small , clinical ly heterogeneous , and of poor quality and external validity . They are useful in highlighting the weakness of the evidence base and problems in performing trials in palliative care Background : Family physicians have an important clinical role in assessment and management of  suspicious skin lesions .  As a result of a previous needs assessment study , an educational intervention based on audit and feedback with opportunity for reflection on practice was introduced to 46 family physicians r and omly allocated to either an intervention ( 23 ) or control group ( 23 ) . As an educational tool , audit allows doctors to systematic ally review their practice and establish the quality of care they provide . When combined with feedback and comparison of clinical performance with peers or st and ards , it has been shown to increase learning and change behavior . Methods : Data based on their own patients , on the correlation between clinical and histologic diagnosis , and excisions of skin lesions were collated and reported to the intervention group . Results : Despite r and omization of the doctors , the patient population of doctors in the intervention and control groups were significantly different in key characteristics , including the types of skin lesions treated . The intervention group of doctors showed improved performance in providing clinical information on pathology requests and in adequate surgical excision of skin lesions . Diagnostic performance did not improve significantly , but physicians ' certainty of diagnosis did . Implication s : This study design has highlighted the difficulty in balancing the use of evidence ‐based educational strategies in an equivalent setting to normal practice with evaluation of performance using measures that include characteristics of practitioners ' patients that can not be controlled The occurrence of an unexpected side effect following the use of Maloprim ( pyrimethamine/dapsone ) for malaria chemosuppression in 3 - 59 months old children in Sierra Leone is reported . As part of a trial of chemoprophylaxis and insecticide-impregnated bed nets , 2000 children received either Maloprim or placebo ; 4 % of children who received Maloprim fortnightly for more than 3 months developed hyperpigmented macules , whereas none of the children who received placebo did so . Histopathological examination of full thickness skin biopsies showed macrophages containing melanin in the dermal layer . Clustering of cases was noted among siblings , suggesting the possible involvement of genetic factors in the pathogenesis of these skin reactions . One child was accidentally re-exposed to Maloprim after the drug had been withdrawn and he developed a severe reaction . No other serious side effect was noted . Hyperpigmented lesions similar to those reported in this study have been described previously in patients with leprosy treated with dapsone , and the dapsone component of Maloprim is the likely cause of the skin reactions seen in children given this drug for malaria chemoprophylaxis CONTEXT The findings of systematic review s ( SRs ) and meta-analyses ( MAs ) are used for clinical decision making . The European Association of Urology has committed increasing re sources into the development of high quality clinical guidelines based on such SRs and MAs . OBJECTIVE In this paper , we have summarised the process of conducting SRs for underpinning clinical practice guidelines under the auspices of the European Association of Urology Guidelines Office . EVIDENCE ACQUISITION The process involves explicit methods and the findings should be reproducible . When conducting a SR , the essential first step is to formulate a clear and answerable research question . An extensive literature search lays the foundation for evidence synthesis . Data are extracted independently by two review ers and any disagreements are resolved by discussion or arbitration by a third review er . EVIDENCE SYNTHESIS In SRs , data for particular outcomes in individual r and omised controlled trials may be combined statistically in a meta- analysis to increase power when the studies are similar enough . Biases in studies included in a SR/MA can lead to either an over estimation or an under estimation of true intervention effect size , result ing in heterogeneity in outcome between studies . A number of different tools are available such as Cochrane Risk of Bias assessment tool for r and omised controlled trials . In circumstances where there is too much heterogeneity , or when a review has included nonr and omised comparative studies , it is more appropriate to conduct a narrative synthesis . The GRADE tool for assessing quality of evidence strives to be a structured and transparent system , which can be applied to all evidence , regardless of quality . A SR not only identifies , evaluates , and summarises the best available evidence , but also the gaps to be targeted by future studies . CONCLUSIONS SRs and MAs are integral in developing sound clinical practice guidelines and recommendations . PATIENT SUMMARY Clinical practice guidelines should be evidence based , and systematic review s and meta-analyses are essential in their production . We have discussed the key steps of conducting systematic review s and meta-analyses in this paper OBJECTIVE To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis . METHODS Three hundred eighty-eight patients who experienced acute optic neuritis between July 1 , 1988 , and June 30 , 1991 , were followed up prospect ively for the development of multiple sclerosis . Consenting patients were reassessed after 10 to 13 years . RESULTS The 10-year risk of multiple sclerosis was 38 % ( 95 % confidence interval , 33%-43 % ) . Patients ( 160 ) who had 1 or more typical lesions on the baseline magnetic resonance imaging ( MRI ) scan of the brain had a 56 % risk ; those with no lesions ( 191 ) had a 22 % risk ( P<.001 , log rank test ) . Among the patients who had no lesions on MRI , male gender and optic disc swelling were associated with a lower risk of multiple sclerosis , as was the presence of the following atypical features for optic neuritis : no light perception vision ; absence of pain ; and ophthalmoscopic findings of severe optic disc edema , peripapillary hemorrhages , or retinal exu date s. CONCLUSIONS The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion ; higher numbers of lesions do not appreciably increase that risk . However , even when brain lesions are seen on MRI , more than 40 % of the patients will not develop clinical multiple sclerosis after 10 years . In the absence of MRI lesions , certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis . This natural history information is a critical input for estimating a patient 's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system Background / methods : One hundred and fifteen patients with clinical ly isolated optic neuritis underwent magnetic resonance imaging ( MRI ) of the brain and spinal cord within 3 months of the onset of symptoms . Results : Eighty one ( 70 % ) patients had brain lesions and 31 ( 27 % ) had cord lesions . Cord lesions were seen in 12 % with a normal brain MRI , 21 % with between one and eight brain lesions , and 45 % with nine or more brain lesions . When the new diagnostic criteria for MS were applied , MRI cord imaging used for evidence of dissemination in time and space allowed a diagnosis of MS in only one additional asymptomatic patient at 1 year , two additional asymptomatic patients at 3 years . Conclusions : Using existing criteria , spinal cord imaging rarely contributes to the diagnosis in patients with clinical ly isolated optic neuritis BACKGROUND To investigate the method ological quality of r and omized controlled trials in three areas of complementary medicine . METHODS The method ological quality of 207 r and omized trials collected for five previously published systematic review s on homeopathy , herbal medicine  ( Hypericum for depression , Echinacea for common cold ) , and acupuncture ( for asthma and chronic headache ) was assessed using a vali date d scale ( the Jadad scale ) and single quality items . RESULTS While the method ological quality of the trials was highly variable , the majority had important shortcomings in reporting and /or methodology . Major problems in most trials were the description of allocation concealment and the reporting of drop-outs and withdrawals . There were relevant differences in single quality components between the different complementary therapies : For example , acupuncture trials reported adequate allocation concealment less often ( 6 % versus 32 % of homeopathy and 26 % of herb trials ) , and trials on herbal extracts had better summary scores ( mean score 3.12 versus 2.33 for homeopathy and 2.19 for acupuncture trials ) . Larger trials published more recently in journals listed in Medline and in English language scored significantly higher than trials not meeting these criteria . CONCLUSION Trials of complementary therapies often have relevant method ological weaknesses . The type of weaknesses varies considerably across interventions OBJECTIVE To discuss the quality of r and omized controlled trials ( RCTs ) in Chinese herbal medicine ( CHM ) with respect to design and methodology , and provide suggestions for further improvement in future clinical trials . METHODS A search of the Cochrane Library was conducted to identify RCTs of CHM on line in July 2005 .  Quality of the RCTs was assessed using a 11-item checklist modified from the revised CONSORT statement , with 2 items specific to CHM ( i.e. herb preparation form and quality control of herbs ) . RESULTS The search yielded 167 RCTs that were selected for assessment . All trials included statements about the interventions , objectives , primary outcome design , statistical methods , and herb preparation form . Although 163 ( 97.6 % ) trials reported inclusion criteria , exclusion criteria were only reported in 26 ( 15.6 % ) trials . Fewer than 10 % of trials clearly stated the r and om allocation sequence generation methods , and only 2.4 % mentioned allocation concealment . The vast majority ( 86.8 % ) of trials were open-label , while only 13.2 % used blinding . Almost half ( 45.5 % ) administered the CHM intervention as a tea or decoction . Only one trial ( 0.6 % ) reported a sample size calculation , and a single trial ( 0.6 % ) discussed quality control of the CHM intervention . CONCLUSION The overall method ologic quality of RCTs in CHM was poor . It is essential to improve the design of future RCTs in this clinical area . RECOMMENDATIONS ( 1 ) Investigator conducting RCTs should have formal training about clinical trial design ; ( 2 ) A flow chart is recommended to ensure that all essential steps of clinical trial design are included . ( 3 ) Conducting pilot studies prior to RCTs may help improve their design ; ( 4 ) Registration of clinical trials and publishing their protocol s prior to enrollment may reduce publication bias and solicit peer review s of the proposed design ; ( 5 ) Collaboration between CHM investigators and traditional medicine academic research centers interested in integrative medicine may lead to quality improvement of RCTs of CHM Background We investigated whether there had been an improvement in quality of reporting for r and omised controlled trials of acupuncture since the publication of the STRICTA and CONSORT statements . We conducted a before- and -after study , comparing ratings for quality of reporting following the publication of both STRICTA and CONSORT recommendations . Methodology and Principal Findings Ninety peer review ed journal articles reporting the results of acupuncture trials were selected at r and om from a wider sample frame of 266 papers . Papers published in three distinct time periods ( 1994–1995 , 1999–2000 and 2004–2005 ) were compared . Assessment criteria were developed directly from CONSORT and STRICTA checklists . Papers were independently assessed for quality of reporting by two assessors , one of whom was blind to information which could have introduced systematic bias ( e.g. date of publication ) . We detected a statistically significant increase in the reporting of CONSORT items for papers published in each time period measured . We did not , however , find a difference between the number of STRICTA items reported in journal articles published before and 3 to 4 years following the introduction of STRICTA recommendations . Conclusions and Significance The results of this study suggest that general st and ards of reporting for acupuncture trials have significantly improved since the introduction of the CONSORT statement in 1996 , but that quality in reporting details specific to acupuncture interventions has yet to change following the more recent introduction of STRICTA recommendations . Wider targeting and revision of the guidelines is recommended OBJECTIVE To assess the feasibility and psychometric properties of a lightweight , automated , ambulatory sternal skin conductance monitor to measure frequency of hot flashes ( HFs ) among breast cancer survivors ( BCSs ) . DESIGN A total of 19 postmenopausal BCSs and 5 premenopausal healthy comparison women participated by wearing the monitor for 24 h during their normal daily activities , including sleep . HFs were assessed using subjective ( diaries , event markers ) and objective ( skin conductance ) methods . RESULTS Problems with subjective reporting of HFs were reported by 35 % of BCSs . Technological problems and discomfort related to wearing the monitor were minimal . A total of 243 HFs were recorded using the skin conductance monitor by 17 BCSs and 5 premenopausal women ( BCS group M = 13.4 ; range , 1 - 30 ) . Subjective reporting of HFs was associated with a 31 - 33 % false-positive rate . Skin conductance monitoring during waking hours was associated with a 30 % false-negative rate . CONCLUSIONS The monitor is a feasible method for objective ly assessing HFs in BCSs . Data support continued use of sternal skin conductance as an objective measure of HF frequency . This technology should prove useful as an objective measure of HFs in future intervention research aim ed at alleviating the symptom and improving quality of life among BCSs BACKGROUND AND OBJECTIVES Primary care physicians ( PCPs ) are uniquely positioned to detect melanoma . Effective educational interventions targeted at PCPs may improve early melanoma detection . A previous in-person Basic Skin Cancer Triage ( BSCT ) 2-hour course demonstrated significant short-term improvement in provider practice s , attitudes , ability , confidence , and knowledge . We conducted a r and omized trial to test the efficacy of the BSCT course implemented as a web-based learning program , compared to a similar ( control ) web-based course on weight assessment . METHODS We recruited a sample of 57 PCPs and 3,341 of their patients from four geographically diverse centers . Skin cancer control activities by PCPs were assessed by physician survey and by chart review and patient telephone interview about their recent visit to their PCP at baseline and at 1 - -2 months and 12 months after course completion . RESULTS Some effect of intervention on skin cancer parameters was self-reported by physicians ; this was not confirmed by patient survey or chart-extracted data . Rates of skin cancer control practice s by PCPs were low across both groups before and after intervention . The positive changes in physician-reported behaviors ( total body skin examination [ TBSE ] ) , intentions ( discuss skin cancer detection ) , confidence ( performing TBSE ) , office practice s , and knowledge ( 58 % skin versus 49 % control ) were neither matched by differences in practice reported by their patients , nor persisted in a longer term follow-up , hence may be attributable to physician recall bias due to the experience of the course or desire to please study investigators and were less dramatic as compared to our previously reported in-person BSCT intervention . Thus this approach by itself appears unlikely to result in improved PCP h and ling of skin cancer issues . CONCLUSIONS Given previous success with our in-person course , the features required to make WBL a more effective tool for medical education must be further explored Background This systematic review up date d and extended the " UK evidence report " by Bronfort et al. ( Chiropr Osteopath 18:3 , 2010 ) with respect to conditions/ interventions that received an ' inconclusive ’ or ' negative ’ evidence rating or were not covered in the report . Methods A literature search of more than 10 general medical and specialised data bases was conducted in August 2011 and up date d in March 2013 . Systematic review s , primary comparative studies and qualitative studies of patients with musculoskeletal or non-musculoskeletal conditions treated with manual therapy and reporting clinical outcomes were included . Study quality was assessed using st and ardised instruments , studies were summarised , and the results were compared against the evidence ratings of Bronfort . These were either confirmed , up date d , or new categories not assessed by Bronfort were added . Results 25,539 records were found ; 178 new and additional studies were identified , of which 72 were systematic review s , 96 were r and omised controlled trials , and 10 were non-r and omised primary studies . Most ' inconclusive ’ or ' moderate ’ evidence ratings of the UK evidence report were confirmed . Evidence ratings changed in a positive direction from inconclusive to moderate evidence ratings in only three cases ( manipulation/mobilisation [ with exercise ] for rotator cuff disorder ; spinal mobilisation for cervicogenic headache ; and mobilisation for miscellaneous headache ) . In addition , evidence was identified on a large number of non-musculoskeletal conditions not previously considered ; most of this evidence was rated as inconclusive . Conclusions Overall , there was limited high quality evidence for the effectiveness of manual therapy . Most review ed evidence was of low to moderate quality and inconsistent due to substantial method ological and clinical diversity . Areas requiring further research are highlighted PURPOSE This manuscript presents evidence -based guidance on the use of vital pulp therapies for treatment of deep caries lesions in children . A guideline panel convened by the American Academy of Pediatric Dentistry formulated evidence -based recommendations on three vital pulp therapies : indirect pulp treatment ( IPT ; also known as indirect pulp cap ) , direct pulp cap ( DPC ) , and pulpotomy . METHODS The basis of the guideline 's recommendations was evidence from " Primary Tooth Vital Pulp Therapy : A Systematic Review and Meta- Analysis . " ( Pediatr Dent 2017;15;39[1]:16 - 23 . ) A systematic search was conducted in PubMed ® / MEDLINE , Embase ® , Cochrane Central Register of Controlled Trials , and trial data bases to identify r and omized controlled trials and systematic review s addressing peripheral issues of vital pulp therapies such as patient preferences of treatment and impact of cost . Quality of the evidence was assessed through the Grading of Recommendations Assessment , Development , and Evaluation approach ; the evidence -to-decision framework was used to formulate a recommendation . RESULTS The panel was unable to make a recommendation on superiority of any particular type of vital pulp therapy owing to lack of studies directly comparing these interventions . The panel recommends use of  mineral trioxide aggregate ( MTA ) and formocresol in pulpotomy treatments ; these are recommendations based on moderate- quality evidence at 24 months . The panel made weak recommendations regarding choice of medicament in both IPT ( moderate- quality evidence [ 24 months ] , low quality evidence [ 48 months ] ) and DPC ( very-low quality evidence [ 24 months ] ) . Success of both treatments was independent of type of medicament used . The panel also recommends use of ferric sulfate  ( low- quality evidence ) , lasers ( low- quality evidence ) ,  sodium hypochlorite  ( very low- quality evidence ) , and  tricalcium silicate  ( very low- quality evidence ) in pulpotomies ; these are weak recommendations based on low- quality evidence . The panel recommended against the use of calcium hydroxide as pulpotomy medicament in primary teeth with deep caries lesions . Conclusions and practical implication s : The guideline intends to inform the clinical practice s with evidence -based recommendations on vital pulp therapies in primary teeth with deep caries lesions . These recommendations are based upon the best available evidence to- date Background R and omised controlled trials ( RCTs ) of complex interventions in primary health care ( PHC ) are needed to provide evidence -based programmes to achieve the Declaration of Alma Ata goal of making PHC equitable , accessible and universal and to effectively address the rising burden from chronic disease . Process evaluations of these RCTs can provide insight into the causal mechanisms of complex interventions , the context ual factors , and inform as to whether an intervention is ineffective due to implementation failure or failure of the intervention itself . To build on this emerging body of work , we aim to consoli date the methodology and methods from process evaluations of complex interventions in PHC and their findings of facilitators and barriers to intervention implementation in this important area of health service delivery . Methods Systematic review of process evaluations of r and omised controlled trials of complex interventions  which address prevalent major chronic diseases in PHC setting s. Published process evaluations of RCTs will be identified through data base and clinical trial registry search es and contact with authors . Data from each study will be extracted by two review ers using st and ardised forms . Data extracted include descriptive items about ( 1 ) the RCT , ( 2 ) about the process evaluations ( such as methods , theories , risk of bias , analysis of process and outcome data , strengths and limitations ) and ( 3 ) any stated barriers and facilitators to conducting complex interventions . A narrative synthesis of the findings will be presented . Discussion Process evaluation findings are valuable in determining whether a complex intervention should be scaled up or modified for other context s. Publishing this protocol serves to encourage transparency in the reporting of our synthesis of current literature on how process evaluations have been conducted thus far and a deeper underst and ing of potential challenges and solutions to aid in the implementation of effective interventions in PHC beyond the research setting . Systematic review registration PROSPERO PURPOSE To describe the health-related quality of life , measured with the National Eye Institute Visual Function Question naire ( NEI-VFQ ) , of patients several years after the onset of optic neuritis , according to their neurologic and visual status ; to assess the relationship between the NEI-VFQ subscales and clinical measures of visual function ; and to assess the internal consistency reliability of the NEI-VFQ subscales . METHODS The NEI-VFQ was administered to 244 patients 5 to 8 years after treatment for an episode of acute optic neuritis as part of the Optic Neuritis Treatment Trial .  Visual acuity , visual field , contrast sensitivity , and color vision were measured at the same time as question naire completion . RESULTS The  NEI-VFQ scores generally were lower than those reported for a disease-free group . Reported dysfunction was greater when multiple sclerosis was present and when visual acuity was abnormal , supporting the construct validity of the NEI-VFQ . Rank correlations between the NEI-VFQ subscales and clinical measures of visual function were moderate at best . Internal consistency reliability was generally high for most of the NEI-VFQ subscales . CONCLUSIONS These findings add support to the use of the NEI-VFQ as a valuable measure of self-reported visual impairment BACKGROUND AND OBJECTIVE To develop a checklist of items measuring the quality of reports of r and omized clinical trials ( RCTs ) assessing nonpharmacological treatments ( NPTs ) . STUDY DESIGN AND SETTING The Delphi consensus method was used to select and reduce the number of items in the checklist . A total of 154 individuals were invited to participate : epidemiologists and statisticians involved in the field of methodology of RCTs ( n = 55 ) , members of the Cochrane Collaboration ( n = 41 ) , and clinicians involved in planning NPT clinical trials ( n = 58 ) . Participants ranked on a 10-point Likert scale whether an item should be included in the checklist . RESULTS Fifty-five experts ( 36 % ) participated in the survey . They were experienced in systematic review s ( 68 % were involved in the Cochrane Collaboration ) and in planning RCTs ( 76 % ) . Three rounds of the Delphi method were conducted to achieve consensus . The final checklist contains 10 items and 5 subitems , with items related to the st and ardization of the intervention , care provider influence , and additional measures to minimize the potential bias from lack of blinding of participants , care providers , and outcome assessors . CONCLUSIONS This tool can be used to critically appraise the medical literature , design NPT studies , and assess the quality of trial reports included in systematic review
The most under-reported items were concealment of allocation , blinding of patients and outcome assessors , intention to treat and validation of outcomes .
BACKGROUND In the process of conducting a systematic review on interventions for skin lesions due to neuritis in leprosy , we assessed several primary papers with respect to the quality of reporting and methods used in the studies .
Awareness of what constitutes weak points in previously conducted studies may be used to improve the planning , conducting and reporting of future clinical trials .
AIMS To assess the quality of reporting and of methodology  in studies of interventions for skin lesions due to neuritis in leprosy .