Showing papers by "Cochrane Collaboration published in 2002"

The marine ecosystem of Kongsfjorden, Svalbard

Abstract: Kongsfjorden is a glacial fjord in the Arctic (Svalbard) that is influenced by both Atlantic and Arctic water masses and harbours a mixture of boreal and Arctic flora and fauna. Inputs from large tidal glaciers create steep environmental gradients in sedimentation and salinity along the length of this fjord. The glacial inputs cause reduced biomass and diversity in the benthic community in the inner fjord. Zooplankton suffers direct mortality from the glacial outflow and primary production is reduced because of limited light levels in the turbid, mixed inner waters. The magnitude of the glacial effects diminishes towards the outer fjord. Kongsfjorden is an important feeding ground for marine mammals and seabirds. Even though the fjord contains some boreal fauna, the prey consumed by upper trophic levels is mainly Arctic organisms. Marine mammals constitute the largest top-predator biomass, but seabirds have the largest energy intake and also export nutrients and energy out of the marine environment. Kongsfjorden has received a lot of research attention in the recent past. The current interest in the fjord is primarily based on the fact that Kongsfjorden is particularly suitable as a site for exploring the impacts of possible climate changes, with Atlantic water influx and melting of tidal glaciers both being linked to climate variability. The pelagic ecosystem is likely to be most sensitive to the Atlantic versus Arctic influence, whereas the benthic ecosystem is more affected by long-term changes in hydrography as well as changes in glacial runoff and sedimentation. Kongsfjorden will be an important Arctic monitoring site over the coming decades and a review of the current knowledge, and a gap analysis, are therefore warranted. Important knowledge gaps include a lack of quantitative data on production, abundance of key prey species, and the role of advection on the biological communities in the fjord.

A brief history of research synthesis

Abstract: Science is supposed to be cumulative, but scientists only rarely cumulate evidence scientifically. This means that users of research evidence have to cope with a plethora of reports of individual studies with no systematic attempt made to present new results in the context of similar studies. Although the need to synthesize research evidence has been recognized for well over two centuries, explicit methods for this form of research were not developed until the 20th century. The development of methods to reduce statistical imprecision using quantitative synthesis (meta-analysis) preceded the development of methods to reduce biases, the latter only beginning to receive proper attention during the last quarter of the 20th century. In this article, the authors identify some of the trends and highlights in this history, to which researchers in the physical, natural, and social sciences have all contributed, and speculate briefly about the "future history" of research synthesis.

Surprisingly small effect of antiviral treatment in patients with hepatitis C.

Abstract: Most patients with hepatitis C virus infection are not candidates for interferon-based therapies; alternative interventions should be sought for these patients.

Melatonin for the prevention and treatment of jet lag

Abstract: Background : Jet-lag commonly affects air travellers who cross several time zones. It results from the body's internal rhythms being out of step with the day-night cycle at the destination. Melatonin is a pineal hormone that plays a central part in regulating bodily rhythms and has been used as a drug to re-align them with the outside world. Objectives : To assess the effectiveness of oral melatonin taken in different dosage regimens for alleviating jet-lag after air travel across several time zones. Search strategy : We searched the Cochrane Controlled Trials Register, MEDLINE, EMBASE, PsychLit and Science Citation Index electronically, and the journals 'Aviation, Space and Environmental Medicine' and 'Sleep' by hand. We searched citation lists of relevant studies for other relevant trials. We asked principal authors of relevant studies to tell us about unpublished trials. Reports of adverse events linked to melatonin use outside randomised trials were searched for systematically in 'Side Effects of Drugs' (SED) and SED Annuals, 'Reactions Weekly', MEDLINE, and the adverse drug reactions databases of the WHO Uppsala Monitoring Centre (UMC) and the US Food & Drug Administration. Selection criteria : Randomised trials in airline passengers, airline staff or military personnel given oral melatonin, compared with placebo or other medication. Outcome measures should consist of subjective rating of jet-lag or related components, such as subjective wellbeing, daytime tiredness, onset and quality of sleep, psychological functioning, duration of return to normal, or indicators of circadian rhythms. Data collection and analysis : Ten trials met the inclusion criteria. All compared melatonin with placebo; one in addition compared it with a hypnotic, zolpidem. Nine of the trials were of adequate quality to contribute to the assessment, one had a design fault and could not be used in the assessment. Reports of adverse events outside trials were found through MEDLINE, 'Reactions Weekly', and in the WHO UMC database. Main results : Nine of the ten trials found that melatonin, taken close to the target bedtime at the destination (10pm to midnight), decreased jet-lag from flights crossing five or more time zones. Daily doses of melatonin between 0.5 and 5mg are similarly effective, except that people fall asleep faster and sleep better after 5mg than 0.5mg. Doses above 5mg appear to be no more effective. The relative ineffectiveness of 2mg slow-release melatonin suggests that a short-lived higher peak concentration of melatonin works better. Based on the review, the number needed to treat (NNT) is 2. The benefit is likely to be greater the more time zones are crossed, and less for westward flights. The timing of the melatonin dose is important: if it is taken at the wrong time, early in the day, it is liable to cause sleepiness and delay adaptation to local time. The incidence of other side effects is low. Case reports suggest that people with epilepsy, and patients taking warfarin may come to harm from melatonin. Reviewer's conclusions : Melatonin is remarkably effective in preventing or reducing jet-lag, and occasional short-term use appears to be safe. It should be recommended to adult travellers flying across five or more time zones, particularly in an easterly direction, and especially if they have experienced jet-lag on previous journeys. Travellers crossing 2-4 time zones can also use it if need be. The pharmacology and toxicology of melatonin needs systematic study, and routine pharmaceutical quality control of melatonin products must be established. The effects of melatonin in people with epilepsy, and a possible interaction with warfarin, need investigation.

Identification of randomized controlled trials in systematic reviews: accuracy and reliability of screening records.

Abstract: A study was conducted to estimate the accuracy and reliability of reviewers when screening records for relevant trials for a systematic review. A sensitive search of ten electronic bibliographic databases yielded 22 571 records of potentially relevant trials. Records were allocated to four reviewers such that two reviewers examined each record and so that identification of trials by each reviewer could be compared with those identified by each of the other reviewers. Agreement between reviewers was assessed using Cohen's kappa statistic. Ascertainment intersection methods were used to estimate the likely number of trials missed by reviewers. Full copies of reports were obtained and assessed independently by two researchers for eligibility for the review. Eligible reports formed the 'gold standard' against which an assessment was made about the accuracy of screening by reviewers. After screening, 301 of 22 571 records were identified by at least one reviewer as potentially relevant. Agreement was 'almost perfect' (kappa>0.8) within two pairs, 'substantial' (kappa>0.6) within three pairs and 'moderate' (kappa>0.4) within one pair. Of the 301 records selected, 273 complete reports were available. When pairs of reviewers agreed on the potential relevance of records, 81 per cent were eligible (range 69 to 91 per cent). If reviewers disagreed, 22 per cent were eligible (range 12 to 45 per cent). Single reviewers missed on average 8 per cent of eligible reports (range 0 to 24 per cent), whereas pairs of reviewers did not miss any (range 0 to 1 per cent). The use of two reviewers to screen records increased the number of randomized trials identified by an average of 9 per cent (range 0 to 32 per cent). Reviewers can reliably identify potentially relevant records when screening thousands of records for eligibility. Two reviewers should screen records for eligibility, whenever possible, in order to maximize ascertainment of relevant trials.

The landscape and lexicon of blinding in randomized trials.

Abstract: Beyond the general understanding of blinding in medical research lies confusion. The authors delve into the landscape and lexicon of blinding in randomized trials in the hope of untangling some of ...

Factors affecting health related quality of life of patients with inflammatory bowel disease

Abstract: Using a disease specific instrument to measure the health related quality of life (HRQOL) of patients with inflammatory bowel disease (IBD), it has been shown that their perceived HRQOL worsens during active disease. The precise factors involved in HRQOL changes reported by these patients are largely unknown. Our aim was to elucidate which socio-demographic and health status variables are related with HRQOL in IBD patients. To this end, 354 patients with IBD were interviewed. To quantify the impairment in the HRQOL, the 36-item version of the inflammatory bowel disease questionnaire (IBDQ) was administered to all patients. To explore the relation of each individual variable on the HRQOL an univariate analysis by using the Spearman correlation, the Mann–Whitney or the Kruskal–Wallis test was performed when necessary. Factors significant at the univariate analysis were assessed using multiple linear regression modeling with global IBDQ score as the dependent factor. Results: Disease type did not predict IBDQ score in the univariate nor in the multivariate analysis. Consequently, statistical analysis was performed in the global group of 354 patients independently of the type of disease. Lower recurrence/year index, longer disease duration, higher level of education, symptom activity, male gender and non-necessity of hospitalization all predict a better HRQOL (p < 0.05). Factors which remained significant (p < 0.05) in the multiple regression modeling were gender, need of hospitalization, symptomatic activity, recurrence/year index and education level. Conclusions: Symptomatic activity and socio-demographic variables such as gender and education are the most important factors involved in the impairment of HRQOL in patients with IBD.

Effects of l-Carnitine Supplementation in Maintenance Hemodialysis Patients: A Systematic Review

Abstract: There are many causes for carnitine depletion during maintenance hemodialysis. Supplementation with L-carnitine in animals has been associated with improvement in some abnormalities also present in chronic renal failure. However, it is still controversial whether restoring plasma or tissue carnitine will correct clinical or biologic symptoms observed in maintenance hemodialysis. A systematic review is here performed to determine the effects of L-carnitine in maintenance hemodialysis patients. Eighty-three prospective trials were identified from 1978 to 1999 in which L-carnitine was randomly allocated in 21 trials. Change in serum triglycerides, cholesterol fractions, hemoglobin levels, erythropoietin dose, and other symptoms (muscle function, exercise capacity, and quality of life) were examined. A total of 482 patients in 18 trials were considered for analysis. There was no effect of L-carnitine on triglycerides, total cholesterol, or any of its fractions. Before the erythropoietin (EPO) era, L-carnitine treatment was associated with improved hemoglobin (P < 0.01) and with a decreased EPO dose (P < 0.01) and improved resistance to EPO when patients routinely received EPO. Muscle function, exercise capacity, and quality of life could not be reliably assessed because of the noncombinable nature of end points and the limited number of trials. In conclusion, L-carnitine cannot be recommended for treating the dyslipidemia of maintenance hemodialysis patients. By contrast, this review suggests a promising effect of L-carnitine on anemia management. The route of L-carnitine administration should be evaluated because there is no evidence as to the most efficient method of administration in maintenance hemodialysis.

Development of the Cochrane Collaboration's CENTRAL Register of controlled clinical trials.

Abstract: The Cochrane Collaboration has established a centralized database of controlled trials and other studies of health care interventions (called CENTRAL) that serves as the best available resource for all those preparing and maintaining systematic reviews or otherwise searching for trials. CENTRAL is available on The Cochrane Library. This article describes the history and methods of CENTRAL’s development and the results of an analysis of the current composition of CENTRAL. As of September 2000, CENTRAL contained almost 300,000 citations to reports of trials, contributed mainly by Cochrane Groups and Centers around the world. Development of CENTRAL has been an ambitious, scholarly undertaking and has resulted in a valuable resource: CENTRAL includes citations to controlled trials that may not be indexed in MEDLINE, EMBASE, or other bibliographic databases; citations published internationally in many languages; and citations that are available only in conference proceedings or other hard-to-access sources.

Publishing protocols of systematic reviews: comparing what was done to what was planned.

Abstract: ContextPublication of research protocols minimizes bias by explicitly stating a priori hypotheses and methods without prior knowledge of results.MethodsWe conducted a retrospective comparative study to assess the extent to which the content of published Cochrane reviews had changed compared with their previously published protocols and to assess any potential impact these changes may have had in introducing bias to the study. We identified previously published protocols for new Cochrane reviews appearing in The Cochrane Library; 2000, issue 3. The texts of published protocols and completed reviews were compared. Two raters independently identified changes to the different sections of the protocol and classified the changes as none, minor, or major.ResultsOf the 66 new Cochrane reviews, we identified a previously published protocol for 47 reviews. Of these, 43 reviews had at least 1 section that had undergone a major change compared with the most recently published protocol. The greatest variation between protocols and reviews was in the methods section, in which 68% of reviews (n = 32) had undergone a major change. Changes made in other sections that may have resulted in the introduction of bias included narrowing of objectives, addition of comparisons or new outcome measures, broadening of criteria for the types of study design included, and narrowing of types of participants included.ConclusionsResearch protocols, even if published, are likely to remain, at least to some extent, iterative documents. We found that a large number of changes were made to Cochrane reviews, some of which could be prone to influence by prior knowledge of results. Even if many of the changes between protocol and review improve the overall study, the reasons for making these should be clearly identified and documented within the final review.

Experience, knowledge and attitudes of mental health staff regarding clients with a borderline personality disorder.

Abstract: A survey of mental health staff experience, knowledge and attitudes regarding the management of clients with a diagnosis of borderline personality disorder (BPD) aimed to obtain baseline data to provide direction for developing planned education and determining staff willingness to participate in such training. A 23-item questionnaire was developed and posted to mental health staff in a public Area Mental Health Service in New South Wales (n = 516). A total of 229 staff completed the questionnaire. Most staff (85%) reported having contact with clients who have a diagnosis of BPD at least once a month or more frequently, with 32% of respondents reporting daily contact. Eighty per cent of respondents found dealing with clients who have a BPD to be moderate to very difficult; 84% of staff felt that dealing with this client group was more difficult than dealing with other client groups. Most staff (82%) believed that, as mental health professionals, they had a role in the assessment, management and referral of clients with BPD, as well as in educating and providing information. Staff readily identified resources which would be helpful to them when working with such clients. It was encouraging to see that the majority of staff (95%) indicated their willingness to gain further education and training in the management of these clients. Although many staff believed they were knowledgeable about and confident in managing these clients, most staff also indicated difficulties posed by these clients and perceived a need for further education and training in this area.

Discussion sections in reports of controlled trials published in general medical journals.

Abstract: ContextReliable interpretation of the results of a controlled trial entails setting its results in the context of similar research. A previous study showed that most reports of controlled trials published in 5 general medical journals in May 1997 were deficient in this respect. We assessed the extent to which reports of controlled trials published in the same 5 journals discussed new results in light of the totality of evidence from other controlled trials.MethodsAssessment of the discussion sections in all 33 reports of randomized trials published during May 2001 in Annals of Internal Medicine, BMJ, JAMA, The Lancet, and The New England Journal of Medicine.ResultsThree reports appeared to have been the first published trials to address the questions studied. In none of the remaining 30 reports were the results of the new trial discussed in the context of an updated systematic review of other trials. Although reference was made to relevant systematic reviews in 3 of these 30 reports, there was no integration, quantitative or qualitative, of the results of the new trials in an update of these reviews. In the remaining 27 reports, there was no evidence that any systematic attempt had been made to set the new results in the context of previous trials.ConclusionsBetween 1997 and 2001, there was no evidence of progress in the proportion of reports of trials published in general medical journals that discussed the new results within the context of, or with reference to, up-to-date systematic reviews of relevant evidence from other controlled trials.

Quality of systematic reviews of economic evaluations in health care

Abstract: ContextReviews performed almost a decade ago showed considerable gaps in the quality of reporting and methods applied to economic evaluations of health care interventions. Measures taken by the research community to address the issue included the promulgation of guidelines and the publicizing of good practice in economic evaluation.MethodsTo assess the quality of methods of systematic reviews, economic evaluations in health care, and reporting methods, we conducted full-text searches of private and public databases for the period 1990 through March 2001 and corresponded with researchers active in the field. A total of 102 reports were identified, but only 39 were included. Quality of systematic reviews was assessed by a 6-item checklist.ResultsQuality of review methods was reasonable, but more attention needs to be paid to search methods and standardization of evaluation instruments. The reviews found consistent evidence of serious methodological flaws in a significant number of economic evaluations. Lack of clear descriptions of methods, lack of explanation and justification for the framework and approach used, and low-quality estimates of effectiveness for the interventions evaluated were the most frequent flaws. Modest improvements in quality of conducting and reporting economic evaluations appear to have taken place in the last decade.ConclusionsProper allocation of resources on the basis of economic evaluations remains uncertain. Editorial teams and regulatory bodies should perform quality assurance based on a single widely accepted and validated standard instrument.

Sensory stimulation of brain-injured individuals in coma or vegetative state: results of a Cochrane systematic review

Abstract: Objectives: To assess the effectiveness of sensory stimulation programmes in patients in coma or vegetative state.Design: Systematic review of randomized control trials (RCT) and nonrandomized controlled clinical trials (CCT) comparing any type of stimulation programmes with standard rehabilitation in patients in coma or vegetative state. The Injuries Group specialized register, the Cochrane Controlled trial register, EMBASE, MEDLINE, CINAHL, PSYCHLIT from 1966 to January 2002 were searched without language restriction. Reference lists of articles were scanned and experts in the area contacted to ”nd other relevant studies. Abstracts and papers found were initially screened by one reviewer. Three reviewers independently identi”ed relevant studies, extracted data and assessed study quality, resolving disagreement by consensus.Outcome measures: Duration of unconsciousness (including coma and vegetative state) de”ned as the time between trauma and objective recovery of the ability to respond to verbal comman...

A systematic review of guided tissue regeneration for periodontal infrabony defects

Abstract: Objectives: To systematically review the evidence for efficacy of guided tissue regeneration (GTR) for infrabony defects. Background: The evidence for the efficacy of GTR has not yet been systematically appraised. Methods: We searched for randomised controlled trials of at least 12 months' follow-up comparing GTR with open flap debridement (OFD). Data sources included electronic databases, hand-searched journals and contact with experts. Screening, data abstraction and quality assessment were conducted independently by multiple reviewers. The primary outcome measure was gain in clinical attachment. Results: For attachment level change, the weighted mean difference between GTR alone and open flap debridement was 1.11 mm (95% CI: 0.63–1.59), chi-square for heterogeneity 31.4 (9 df ), P < 0.001) and for GTR + bone substitutes was 1.25 mm (95% CI: 0.89–1.61, chi-square for heterogeneity 0.01 (1 df), P = 0.91). The number of sites needed to treat (NNT) for GTR to achieve one extra site gaining 2 mm or more attachment over open flap debridement was 8 (95% CI: 4–33). Heterogeneity between studies was highly statistically significant for all principal comparisons and could not be explained satisfactorily by sensitivity analyses. Conclusions: Overall, GTR was more effective than OFD in improving attachment levels. However, there was marked variability between studies and general conclusions about the clinical benefit of GTR are limited by this heterogeneity. Future studies should aim to identify factors associated with achieving consistent benefits over open flap debridement. Open flap surgery should remain the control comparison in these studies.

Inflation of type I error rate in two statistical tests for the detection of publication bias in meta-analyses with binary outcomes.

Abstract: The use of meta-analysis to combine results of several trials is still increasing in the medical field. The validity of a meta-analysis may be affected by various sources of bias (for example, publication bias, language bias). Therefore, an analysis of bias should be an integral part of any systematic review. Statistical tests and graphical methods have been developed for this purpose. In this paper, two statistical tests for the detection of bias in meta-analysis were investigated in a simulation study. Binary outcome data, which are very common in medical applications, were considered and relative effect measures (odds ratios, relative risk) were used for pooling. Sample sizes were generated according to findings in a survey of eight German medical journals. Simulation results indicate an inflation of type I error rates for both tests when the data are sparse. Results get worse with increasing treatment effect and number of trials combined. Valid statistical tests for the detection of bias in meta-analysis with sparse data need to be developed.

Systematic review of sexual problems: epidemiology and methodology.

Abstract: We conducted a comprehensive systematic literature review of five sexual problems in order to estimate their population prevalence and to investigate issues arising from the reviewing of epidemiological literature. Two independent reviewers scrutinized abstracts, extracted data, and assessed methodological quality. Twenty-eight relevant studies were identified. Prevalence figures varied considerably, and meta-analysis was not possible because of heterogeneity in study quality and design. Prevalence depends on case definition, characteristics of the study population, and time frame of the prevalence estimates, therefore, design, implementation, and reporting of epidemiological studies needs standardization before systematic reviews and meta-analyses can be carried out.

Method for recommending indexes and materialized views for a database workload

Abstract: The invention herein provides method and apparatus, including software for determining a set of materialized views or indices of the contents or a subset of the contents of a database in a data processing system to be created for one or more users of the database The method and apparatus provide method and means for evaluating a workload presented by a user to the database; evaluating the data processing system characteristics; evaluating the database characteristics; and, using the above evaluations for recommending a set of suitable materialized views or indices to the user Another aspect of the invention, which may be used for a workload presented by a user of a database in a data processing system, provides method and apparatus, including software for determining a set of materialized views or indices of the contents or a subset of the contents of the database, by: generating a plurality of materialized view candidates from evaluation of the workload, data processing system characteristics and database characteristics; estimating statistics for the materialized view candidates such as the number of rows, row size, and column statistics; generating a plurality of potential index candidates by evaluating the workload, data processing system characteristics, database characteristics and the materialized view candidates; and, from the materialized view candidates and index candidates selecting a set of suitable materialized views and/or indices for submission to the user

System and method for incrementally maintaining non-distributive aggregate functions in a relational database

Abstract: A system for incrementally maintaining non-distributive aggregate functions in a relational database includes a data storage device in which a relational database is stored. A processor communicates with the data storage device and includes a database maintenance module. The database maintenance module includes a program for incrementally maintaining non-distributive aggregate functions in a relational database. The method embodied in the program includes determining whether all functions in a relational database query are distributive. Based on this determination, a basic propagate phase graph is selectively altered to yield a new propagate phase graph. Changes to an automatic summary table are then applied thereto based on the new propagate phase graph.

Randomized controlled trials in schizophrenia: a critical perspective on the literature.

Abstract: Objective: The randomized trial provides an opportunity to minimize the inclusion of biases in the evaluation of interventions in psychiatry. Difficulties arise, however, when applying their results to `real world' clinical practice and decision-making. We, therefore, examined the real world applicability of schizophrenia trials. Method: A narrative overview of the content and quality of the randomized trials relevant to the care of those with schizophrenia is provided. Results: Complex, explanatory, under-powered randomized drug trials dominate evaluative research in schizophrenia. Conclusion: Explanatory designs are a necessary but insufficient step in establishing the true worth of interventions in schizophrenia. Research from other spheres of mental health and wider health care suggest that pragmatic trials are feasible. This design allows large scale trials to be conducted which include patients which we would recognize from routine practice and which record outcomes which are of genuine interest to decision-makers.

Adverse effects of the antimalaria drug, mefloquine: due to primary liver damage with secondary thyroid involvement?

Abstract: Mefloquine is a clinically important antimalaria drug, which is often not well tolerated. We critically reviewed 516 published case reports of mefloquine adverse effects, to clarify the phenomenology of the harms associated with mefloquine, and to make recommendations for safer prescribing. We postulate that many of the adverse effects of mefloquine are a post-hepatic syndrome caused by primary liver damage. In some users we believe that symptomatic thyroid disturbance occurs, either independently or as a secondary consequence of the hepatocellular injury. The mefloquine syndrome presents in a variety of ways including headache, gastrointestinal disturbances, nervousness, fatigue, disorders of sleep, mood, memory and concentration, and occasionally frank psychosis. Previous liver or thyroid disease, and concurrent insults to the liver (such as from alcohol, dehydration, an oral contraceptive pill, recreational drugs, and other liver-damaging drugs) may be related to the development of severe or prolonged adverse reactions to mefloquine. We believe that people with active liver or thyroid disease should not take mefloquine, whereas those with fully resolved neuropsychiatric illness may do so safely. Mefloquine users should avoid alcohol, recreational drugs, hormonal contraception and co-medications known to cause liver damage or thyroid damage. With these caveats, we believe that mefloquine may be safely prescribed in pregnancy, and also to occupational groups who carry out safety-critical tasks. Mefloquine's adverse effects need to be investigated through a multicentre cohort study, with small controlled studies testing specific elements of the hypothesis.

Iodised salt for preventing iodine deficiency disorders.

Abstract: Background Iodine deficiency is the main cause for potentially preventable mental retardation in childhood, as well as causing goitre and hypothyroidism in people of all ages. It is still prevalent in large parts of the world. Objectives To assess the effects of iodised salt in comparison with other forms of iodine supplementation or placebo in the prevention of iodine deficiency disorders. Search methods We searched The Cochrane Library, MEDLINE, the Register of Chinese trials developed by the Chinese Cochrane Centre, and the Chinese Med Database, China National knowledge Infrastructure, and searched reference lists, databases of ongoing trials and the Internet. Selection criteria We included prospective controlled studies of iodised salt versus other forms of iodine supplementation or placebo in people living in areas of iodine deficiency. Studies reported mainly goitre rates and urinary iodine excretion as outcome measures. Data collection and analysis The initial data selection and quality assessment of trials was done independently by two reviewers. Subsequently, after the scope of the review was slightly widened from including only randomised controlled trials to including non-randomised prospective comparative studies, a third reviewer repeated the trials selection and quality assessment. As the studies identified were not sufficiently similar and not of sufficient quality, we did not do a meta-analysis but summarised the data in a narrative format. Main results We found six prospective controlled trials relating to our question. Four of these were described as randomised controlled trials, one was a prospective controlled trial that did not specify allocation to comparison groups, and one was a repeated cross-sectional study comparing different interventions. Comparison interventions included non-iodised salt, iodised water, iodised oil, and salt iodisation with potassium iodide versus potassium iodate. Numbers of participants in the trials ranged from 35 to 334; over 20,000 people were included in the cross-sectional study. Three studies were in children only, two investigated both groups of children and adults and one investigated pregnant women. There was a tendency towards goitre reduction with iodised salt, although this was not significant in all studies. There was also an improved iodine status in most studies (except in small children in one of the studies), although urinary iodine excretion did not always reach the levels recommended by the WHO. None of the studies observed any adverse effects of iodised salt. Authors' conclusions The results suggest that iodised salt is an effective means of improving iodine status. No conclusions can be made about improvements in other, more patient-oriented outcomes, such as physical and mental development in children and mortality. None of the studies specifically investigated development of iodine-induced hyperthyroidism, which can be easily overlooked if just assessed on the basis of symptoms. High quality controlled studies investigating relevant long term outcome measures are needed to address questions of dosage and best means of iodine supplementation in different population groups and settings.

Single dose dipyrone for acute renal colic pain.

Abstract: Background Renal colic pain is extremely painful and requires immediate treatment with strong analgesics. Dipyrone is the most popular non-opioid first line analgesic in many countries but in others it has been banned (e.g. USA, UK) because of its association with blood dyscrasias such as agranulocytosis. Since dipyrone is used in many countries (e.g. Brazil, Spain) there is a need to determine the benefits and harms of its use to treat renal colic pain. Objectives Assess quantitatively the analgesic efficacy and adverse effects of single-dose dipyrone in adults with moderate to severe renal colic pain. Search methods Published reports were identified from electronic databases (MEDLINE, EMBASE, The Cochrane Library, LILACS) and additional studies were identified from the reference lists of retrieved reports. Date of the most recent search: January 2000. Selection criteria Inclusion criteria were: full journal publication; RCT with a double-blind design; adult patients with baseline renal colic pain of moderate or severe intensity; treatment arms which included dipyrone (oral, intramuscular or intravenous administration) and a control; single dose data. Data collection and analysis Summed pain intensity and pain relief data were extracted and converted into dichotomous information to yield the number of patients with at least 50% pain relief over 15-30 minutes, 1-2 hours and six hours. The proportion of patients with at least 50% pain relief was calculated. Single dose adverse effect data were collected. Main results Eleven studies with 1053 patients (550 on dipyrone) met the inclusion criteria. Unfortunately, few data were available for analysis; most analyses were based on the results of single, small trials and statistical pooling of the results was inappropriate. Efficacy estimates were calculated as the weighted mean percent of patients achieving at least 50% pain relief with the range of values from trials contributing to the analysis. However, these estimates were not robust. Commonly reported adverse effects with intravenous dipyrone were dry mouth and somnolence, and one study reported pain at the injection site. Insufficient information was available for safety analyses. Authors' conclusions Limited available data indicated that single dose dipyrone was of similar efficacy to other analgesics used in renal colic pain, although intramuscular dipyrone was less effective than diclofenac 75 mg. Combining dipyrone with antispasmolytic agents did not appear to improve its efficacy. Intravenous dipyrone was more effective than intramuscular dipyrone. Dry mouth and somnolence were commonly reported with intravenous dipyrone. None of the studies reported agranulocytosis.

Ursodeoxycholic acid and/or antibiotics for prevention of biliary stent occlusion.

Abstract: BACKGROUND Malignant biliary obstruction, which requires endoscopic stenting as palliative therapy, is often complicated by clogging of the stent with subsequent jaundice and/or cholangitis. Stent clogging may be caused by microbiological adhesion and biliary stasis. Therefore, antibiotics and choleretic agents like ursodeoxycholic acid (UDCA) have been investigated to see whether they prolong stent patency. OBJECTIVES To evaluate if UDCA and/or antibiotics may prolong stent patency and survival in patients with strictures of the biliary tract and endoscopically inserted stents. SEARCH STRATEGY The Trials Register of The Cochrane Hepato-Biliary Group, The Cochrane Library, MEDLINE, Current Contents, EMBASE, and CancerLit were searched until June 2001. Reference lists of the identified articles were checked for further trials. SELECTION CRITERIA All randomised or quasi-randomised clinical trials investigating UDCA and/or antibiotics in patients with biliary stents were considered for inclusion, regardless of blinding, language, and publication status. DATA COLLECTION AND ANALYSIS Trial inclusion, quality assessment, and data extraction were performed independently by two reviewers. Principal investigators were contacted for further information. Survival data were combined by using hazard ratios (with 95% confidence interval (95% CI)). MAIN RESULTS Five non-blinded randomised trials with 258 patients with malignant strictures treated with polyethylene stents were included. Three trials, including 152 patients, investigated a combination of UDCA and antibiotics versus no treatment. The meta-analysis of these three trials does not show a significant treatment effect on the duration of stent patency (hazard ratio (random effects model) 0.58, 95% CI 0.22 to 1.54) or mortality (hazard ratio (fixed effect model) 0.99, 95% CI 0.68 to 1.43). Two trials with 106 patients compared antibiotics with no treatment, one of these trials used a combination of antibiotics and rowachol (an 'alternative' drug of the 'mint' family). The pooled results of these two trials do not show significant effects of antibiotics on the duration of stent patency (hazard ratio (fixed effect model) 0.69 (95% CI 0.37 to 1.30)) or mortality (hazard ratio (fixed effect model) 1.23 (95% CI 0.72 to 2.08). Data concerning duration of hospital stay, frequency of cholangitis, and rate of infectious complications due to selection of antibiotic resistant bacteria strains were not available. REVIEWER'S CONCLUSIONS Treatment with UDCA and/or antibiotics to prevent clogging of biliary stents in patients with malignant stricture of the biliary tract cannot be recommended routinely on the basis of the existing randomised clinical trials. Further trials are needed with rigorous methodology and sufficient statistical power.

Placebo treatment versus no treatment

Abstract: Background Placebo interventions are often believed to improve patient reported and observer reported outcomes, but this belief is not based on evidence from randomised trials that compare placebo with no treatment. Objectives To assess the effect of placebo interventions. Search strategy We searched the Cochrane Controlled Trials Register (The Cochrane Library, issue 3, 1998), MEDLINE (Jan 1966 to Dec 1998), EMBASE (Jan 1980 to Dec 1998), Biological Abstracts (Jan 1986 to Dec 1998), PsycLIT (Jan 1887 to Dec 1998). Experts on placebo research were contacted and references in the included trials were read. Selection criteria Randomised placebo trials with a no-treatment control group investigating any health problem were included. Data collection and analysis Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. Main results Outcome data were available in 114 out of 130 included trials, investigating 40 clinical conditions. Outcomes were binary in 32 trials (3795 patients) and continuous in 82 (4730 patients). We found no statistically significant pooled effect of placebo in studies with binary outcomes, relative risk 0.95 (95 per cent confidence interval 0.88 to 1.02). The pooled relative risk for subjective (patient reported) outcomes was 0.95 (0.86 to 1.05) and for objective (observer reported) outcomes 0.91 (0.80 to 1.04). There was statistically significant heterogeneity (P < 0.03), but no evidence of sample size bias (P = 0.56). We found an overall positive effect of placebo treatments in trials with continuous outcomes, standardised mean difference -0.28 (95 per cent confidence interval -0.38 to -0.19). The standardised mean difference for subjective outcomes was -0.36 (-0.47 to -0.25), whereas no statistically significant effect was found for objective outcomes, standardised mean difference -0.12 (-0.27 to 0.03). There was statistically significant heterogeneity (P < 0.001), and evidence of sample size bias (P = 0.05). There was no statistically significant effect of placebo interventions in eight out of nine clinical conditions investigated in three trials or more (nausea, relapse in prevention of smoking and depression, overweight, asthma, hypertension, insomnia and anxiety), but confidence intervals were wide. There was a modest apparent analgesic effect of placebo interventions, standardised mean difference -0.27 (-0.40 to -0.15), but also a substantial risk of bias. Reviewers' conclusions There was no evidence that placebo interventions in general have clinically important effects. A possible moderate effect on subjective continuous outcomes, especially pain, could not be clearly distinguished from bias.

Terbinafine in fungal infections of the nails: a meta‐analysis of randomized clinical trials

Abstract: SummaryBackground Historically, there has been a general resistance to treating onychomycosis on the basis that such treatments were protracted and of uncertain outcome. However, modern treatments act more promptly and reliably. Objectives To carry out a meta-analysis to evaluate the efficacy and safety of terbinafine in comparison with placebo, itraconazole and griseofulvin. Methods The analysis used data from published trials, supplemented where necessary by reference to the original trial reports. Results Three trials were included in which terbinafine was compared with placebo. From four trials comparing terbinafine with itraconazole, a statistically significant advantage in favour of terbinafine was observed for negative culture and microscopy at the end of the trials. Furthermore, both patients and physicians reported terbinafine to be better tolerated than itraconazole. From two trials comparing terbinafine with griseofulvin, a significantly higher rate of negative microscopy and culture was observed with terbinafine. Conclusions A significant advantage in favour of treatment with terbinafine was observed.

Method and apparatus for modeling dataflow systems and realization to hardware

Abstract: A method of modelling a processing system comprising the steps of: storing in a memory indicia representative of a data flow component responsive to at least a data signal and a valid signal; in a processor simulating a data flow operation from characteristics of said data flow component.