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Combined hormonal contraception and bone health: a systematic review.

This systematic review examined whether women who use combined hormonal contraception experience changes in risk of fracture or bone mineral density (BMD) that differ from nonusers. We identified 86 articles from PubMed and EMBASE (published 1966 to August 2005) that reported on fracture or BMD outcomes by use of combined hormonal contraceptives. The evidence relating to combined oral contraceptives (COCs) and fracture is inconclusive, as results from the available studies conflict. Studies of adolescent and young adult women generally found lower BMD among COC users than nonusers. Evidence for premenopausal adult women suggested no differences in BMD between COC users and nonusers. COC use in perimenopausal and postmenopausal women preserved bone mass, while nonusers lost BMD, but BMD among former COC users in this age group was the same as for never-users. Evidence for other combined hormonal methods was very limited, with one study indicating no effect of combined hormonal injectable use among premenopausal women on BMD and one study suggesting lower BMD among premenopausal users of the NuvaRing than in nonusers.

Age Factors↗

[Treatment of osteoporosis with calcium and vitamin D. Systematic review].

BACKGROUND: Systematic review of the efficacy of calcium and vitamin D for the treatment of osteoporosis. MATERIAL AND METHOD: Review of the database MEDLINE between 1996 and may 1998, by the key words: osteoporosis, calcium, vitamin D (and related terms) and randomized clinical trial. Review of the electronic versions of Best Evidence, The Cochrane Library, congress abstracts and references from two main textbooks. Ascending review of the literature. All the reviews were performed independently by two of the authors. Design parameters and main results of the primary publications of the identified trials were tabulated. Two independent observers carried out methodological scoring of the studies. Results were tabulated and a judgement made for the results. RESULTS: Eleven studies on calcium, 8 of vitamin D and 12 about calcitriol and other hormone derivatives were included. Studies with calcium were mainly performed on non-clinical populations and in three anti-fracture efficacy was analyzed. Results were positive in population with low baseline intake and substantial supplementation. Trials on vitamin D were done in non-clinical and on institutionalized populations. Trials with calcitriol were developed mainly in osteoporotic fracture populations and reached poorer methodological validity scores. Heterogeneity of the studies precluded a meta-analysis of the different treatments. Studies on calcium showed clinical efficacy in a more consistent way. Inter-observer score was good (kappa = 0.81) and there were no significant correlations between sample size and effect in the different studies. CONCLUSIONS: Calcium treatment is efficacious in populations with low intake receiving substantial supplementation. Vitamin D is efficacious associated with calcium mainly in deficient populations. Efficacy of calcitriol and other derivatives is more controversial.

Calcitriol↗

Can parents rate their child's health-related quality of life? Results of a systematic review.

A systematic review was conducted to determine the relationship between ratings of children's health-related quality of life (HRQoL) made by parents and children. This was investigated in relation to four questions: is agreement greater for some domains (e.g. physical HRQoL) than others?; do parents perceive illness to have a greater impact than their child?; how is agreement affected by child age, gender and illness status?; and is the relationship between proxy ratings affected by the method of data collection? Fourteen studies were identified. Consistent with previous research, there was greater agreement for observable functioning (e.g. physical HRQoL), and less for non-observable functioning (e.g. emotional or social HRQoL). Three studies assessed whether parents perceive the illness to have a greater impact than their child, but no clear conclusions could be drawn given differences in measures used. Agreement is better between parents and chronically sick children compared with parents and their healthy children, but no effects were found for age or gender. All of these results may be dependent on the specific measure of HRQoL employed. There remain strong arguments for obtaining information from both parents and children whenever possible.

Adolescent↗

The efficacy of omega-3 fatty acids on cognitive function in aging and dementia: a systematic review.

We systematically reviewed the published literature on the effects of omega-3 fatty acids on measures of cognitive function in normal aging, incidence and treatment of dementia. Computerized databases were searched for published literature to identify potentially relevant studies with the intent to conduct a meta-analysis. We screened 5,865 titles, reviewed 497 studies of which 49 underwent a detailed review, and found 5 studies that pertained to our objectives. We included controlled clinical trials and observational studies, including prospective cohort, case-control, and case series designs; we excluded case reports. We had no language restrictions. We abstracted data on the effects of omega-3 fatty acids and on study design, relevant outcomes, study population, source, type, amount, and duration of omega-3 fatty acid consumption, and parameters of methodological quality. A single cohort study has assessed the effects of omega-3 fatty acids on cognitive function with normal aging and found no association for fish or total omega-3 consumption. In four studies that assessed the effects of omega-3 fatty acids on incidence and treatment of dementia, a trend in favor of omega-3 fatty acids (fish and total omega-3 consumption) toward reducing risk of dementia and improving cognitive function was reported. The available data are insufficient to draw strong conclusions about the effects of omega-3 fatty acids on cognitive function in normal aging or on the incidence or treatment of dementia. However, limited evidence suggests a possible association between omega-3 fatty acids and reduced risk of dementia.

Aging↗

Does high fructose consumption trigger microglia activation and neuroinflammation? A systematic review.

This systematic review evaluated the effects of fructose intake on neuroinflammatory markers in rodent models. The search terms Fructose AND neuroinflammation OR Neurodegeneration OR chemokines OR interleukins OR microglia OR behaviour OR memory OR cognition were used in Google Scholar, Scopus and Web of Science. Thirteen animal studies investigating fructose-induced neuroinflammation that matched the eligibility criteria were included in the study. Across the studies, 16 inflammatory markers were identified and significantly altered following exposure to fructose. The findings consistently demonstrated elevated expression of pro-inflammatory cytokines, TNF-α, IL-6, and IL-1β, following fructose administration. Fructose consumption also dysregulated MCP-1, fractalkine, and CX3CR1 levels, thereby promoting inflammatory signalling and microglial activation. Furthermore, fructose exposure significantly increased IBA-1 and CD11b, indicating sustained neuroimmune activation. Alterations in important inflammatory pathways involving TLR4, NLRP3, NF-κB, MyD88, iNOS, and cyclooxygenases (COX-1 and COX-2) were also observed. In contrast, expression of the anti-inflammatory regulator peroxisome proliferator-activated receptor gamma (PPARγ) was reduced after fructose treatment. Overall, the findings suggest that chronic fructose consumption induces neuroinflammation through multiple inflammatory and immune-related mechanisms in the brain. These effects appear to be dose- and duration-dependent and may contribute significantly to neurodegeneration and cognitive impairment.

Microglia↗

Assessing the information needs of post-myocardial infarction patients: a systematic review.

We systematically reviewed studies examining information needs of post-myocardial infarction patients and their families. Electronic databases and bibliographies of relevant papers were searched and experts in the field contacted to find relevant studies. A standardised data form was used to extract data on study populations, instruments and results. Of 14 published studies, 6 used the same instrument. Information about risk factors ranked as the most important category overall, followed by information on cardiac anatomy and physiology, medications, and physical activity. Information about miscellaneous items, diet, psychological factors, and the CCU, although ranked lower, were still rated important. Some variation between settings was evident. Patients preferred physicians over nurses as information givers. Differences were found between patient and nurse ratings of information categories. Differences were found in the self-perceived information needs of patients responding to different instruments, indicating a priming effect. Changes in ranking of information categories between CCU, PCCU and PD are congruent with decreasing levels of patient dependency. The information needs of women and other post-MI subgroups, including the elderly, minority ethnic groups, patients with severe coronary disease, and deprived patients, have not been assessed. Patients have not been involved in the design of information needs assessment instruments.

Aftercare↗

Long-term dental arch changes after rapid maxillary expansion treatment: a systematic review.

This systematic review evaluates long-term dental arch changes after rapid maxillary expansion treatment on orthodontic patients with constricted arches. Clinical trials that assessed dental arch changes through measurements on dental casts or cephalometric radiographs were selected. No patients with surgical or other simultaneous treatment during the active expansion period were accepted. Electronic databases were searched with the help of a senior Health Sciences librarian. Original articles were retrieved from the selected abstracts, and their references were also scanned for possible missing articles. Forty-one articles met the initial inclusion criteria, but 35 were later rejected because they lacked a control group or only evaluated dental changes or used a semirapid technique. Some of them also lacked a reported measurement error. From the remaining articles, two did not report a long-term evaluation. From the final four articles, two measured changes through dental casts and two assessed changes through radiographs (one through lateral cephalometric radiographs and one through posteroanterior radiographs). Similar maxillary molar and cuspid expansion could be found in adolescents and young adults. Significantly less indirect mandibular molar and cuspid expansion was attained in young adults compared with adolescents. A significant overall gain in the maxillary and mandibular arch perimeter was found in adolescents. More transverse dental arch changes were found after puberty as compared with before, but the difference may not be clinically significant. No anteroposterior dental changes were found on lateral cephalometric radiographs.

Adolescent↗

Statin safety: a systematic review.

A systematic review of cohort studies, randomized trials, voluntary notifications to national regulatory authorities, and published case reports was undertaken to assess the incidence and characteristics of adverse effects in patients treated with 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, or statins. For statins other than cerivastatin, the incidence of rhabdomyolysis in 2 cohort studies was 3.4 (1.6 to 6.5) per 100,000 person-years, an estimate supported by data from 20 randomized controlled trials. Case fatality was 10%. Incidence was about 10 times greater when gemfibrozil was used in combination with statins. Incidence was higher (4.2 per 100,000 person-years) with lovastatin, simvastatin, or atorvastatin (which are oxidized by cytochrome P450 3A4 [CYP3A4], which is inhibited by many drugs) than pravastatin or fluvastatin (which are not oxidized by CYP3A4). In persons taking simvastatin, lovastatin, or atorvastatin, 60% of cases involved drugs known to inhibit CYP3A4 (especially erythromycin and azole antifungals), and 19% involved fibrates, principally gemfibrozil. The incidence of myopathy in patients treated with statins, estimated from cohort studies supported by randomized trials, was 11 per 100,000 person-years. For liver disease, randomized trials reported fewer hepatobiliary disorders in patients allocated statins than in those allocated placebo. The notification rate of liver failure to regulatory authorities was about 1 per million person-years of statin use. Randomized trials show no excess of renal disease or proteinuria in statin-allocated participants, and the decline in glomerular filtration rate was smaller with statins than with placebo. Evidence from 4 cohort studies and case reports suggests that statins cause peripheral neuropathy, but the attributable risk is small (12 per 100,000 person-years). No change in cognitive function was found in randomized trials of statins in elderly patients.

Adverse Drug Reaction Reporting Systems↗

Clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for Alzheimer's disease. A systematic review.

OBJECTIVES: Systematic review of the clinical and cost-effectiveness of donepezil, rivastigmine, and galantamine for people suffering from Alzheimer's disease. METHODS: Sixteen electronic databases (including MEDLINE, the Cochrane Library, and Embase) and bibliographies of related papers were searched for published/unpublished English language studies, and experts and pharmaceutical companies were consulted for additional information. Randomized controlled trials (RCTs) and economic studies were selected. Clinical effectiveness was assessed on measurement scales assessing progression of Alzheimer's disease on the person's global health, cognition, functional ability, behavior and mood, and quality of life. Cost-effectiveness was presented as incremental cost per year spent in a nonsevere state (by Mini Mental Health State Examination) or quality-adjusted life-year. RESULTS: Twelve of 15 RCTs included were judged to be of good quality. Although donepezil had beneficial effects in Alzheimer's patients on global health and cognition, rivastigmine on global health, and galantamine on global health, cognition, and functional scales, these improvements were small and may not be clinically significant. Measures of quality of life and behavior and mood were rarely assessed. Adverse effects were usually mild and transient. Cost-effectiveness base case estimates ranged from 2,415 Pounds savings to 49,476 Pounds additional cost (1997 prices) per unit of effect for donepezil and a small savings for rivastigmine. Estimates were not considered robust or generalizable. CONCLUSIONS: Donepezil, rivastigmine, and galantamine appear to have some clinical effect for people with Alzheimer's disease, although the extent to which these translate into real differences in everyday life remains unclear. Due to the nature of current economic studies, cost-effectiveness remains uncertain and the impact on different care sectors has been inadequately investigated. Further research is needed to establish the actual benefits of acetylcholinesterase inhibitors (AChEls) for people with Alzheimer's disease and their caregivers, the relationship of these changes to clinical management, and careful prospective evaluation of resource and budgetary consequences.

Aged↗

Reading systematic reviews.

BACKGROUND: While systematic reviews should be of assistance in decision making, currently many reviews are unreliable, poorly reported or not clinically useful. It is therefore important that they are read critically. OBJECTIVES: The objective is to provide a logical way to appraise systematic reviews. Particular objectives are to demonstrate how to use a validated general guide for appraising systematic reviews; amend the guide so that it can be used to appraise systematic reviews of controlled trials, prognostic studies and studies evaluating diagnostic tests; choose between discordant reviews and assess the usefulness of good systematic reviews. DISCUSSION: Guidelines for undertaking and reporting systematic reviews should eventually improve their quality and usefulness. In the meantime, reviews must be appraised critically, particularly those outside the Cochrane Library.

Data Interpretation, Statistical↗

Incontinence-specific quality of life measures used in trials of treatments for female urinary incontinence: a systematic review.

This systematic review examined the use of incontinence-specific quality of life (QOL) measures in clinical trials of female incontinence treatments, and systematically evaluated their quality using a standard checklist. Of 61 trials included in the review, 58 (95.1%) used an incontinence-specific QOL measure. The most commonly used were IIQ (19 papers), I-QoL (12 papers) and UDI (9 papers). Eleven papers (18.0%) used measures which were not referenced or were developed specifically for the study. The eight QOL measures identified had good clinical face validity and measurement properties. We advise researchers to evaluate carefully the needs of their specific study, and select the QOL measure that is most appropriate in terms of validity, utility and relevance, and discourage the development of new measures. Until better evidence is available on the validity and comparability of measures, we recommend that researchers consider using IIQ or I-QOL with or without UDI in trials of incontinence treatments.

Clinical Trials as Topic↗

Prognostic factors for progression of childhood optic pathway glioma: a systematic review.

A systematic literature review was carried out to evaluate best existing evidence on prognostic factors for progression of childhood optic pathway glioma. Databases were searched for relevant articles and articles selected independently by two authors. Information about study design, population, treatment, outcome and prognostic analysis were abstracted and the quality of each article was assessed. A total of 23 articles met the inclusion criteria. Many studies had important methodological limitations, regarding external and internal validity. Eleven studies evaluated possible prognostic factors in a multivariate analysis. Three high-quality studies indicated age<1 year as an independent prognostic factor for a worse progression-free survival. Three studies with multivariate analysis, including one high-quality study, found that children with neurofibromatosis type 1 (NF-1) have a better progression-free survival than those without NF-1. Two studies with multivariate analysis found tumour site to be a prognostic factor, both with some methodological limitations. In conclusion, this systematic review demonstrates that only a few of the prognostic factors proposed have been proven to be clinically relevant. Age<1 year is a clear and independent prognostic factor for progression-free survival. Other prognostic factors, such as NF-1, tumour site and others, are suggested, but are still without solid evidence and need further high-quality studies to be clearly proven.

Disease Progression↗

[Evidence-based medicine. 3. Systematic reviews: a tool for clinical practice, permanent education and health policy decisions. Italian Group on Evidence-Based Medicine-GIMBE].

The reviews of research, summarizing a great amount of studies in a manageable format, are invaluable tools for physicians, inundated with enormous amount of biomedical information. However, narrative reviews are often misleading because, mixing together opinions of authors and results of research, the relation between clinical recommendation and evidence is partial and based on a biased citation of primary studies. In contrast to narrative reviews, the systematic reviews assemble, critically appraise, and synthesize the results of primary studies addressing a specific topic. Additionally their authors use strategies for minimizing bias and random error. The science of systematic reviews is now supported by the Cochrane Collaboration, an international network established for "preparing, maintaining and disseminating systematic reviews of the effects of health care". The authors provide tools for searching, critically appraising and using in practice the systematic reviews, which use can help physicians to improve the transfer of research in clinical practice, a task obliged by limitation of financial resources to physicians of any health service.

Bibliographies as Topic↗

Assisted reproductive technologies and birth outcomes: overview of recent systematic reviews.

Several systematic reviews have been published recently on birth outcomes of infants conceived through assisted reproductive technologies (ART), compared with infants conceived spontaneously. These outcomes include perinatal mortality, preterm birth, low birthweight and birth defects. Methodological limitations of many of the individual studies (including small sample size, potential for bias in ascertainment of outcomes and considering singletons and multiples together) were obviated in these reviews by excluding studies where methods were considered inadequate, by conducting meta-analyses using data from all methodologically sound studies (small and large) and by examining singletons separately. Overall, the reviews indicate few differences between outcomes in ART twins compared with twins conceived spontaneously. However, in singleton ART infants, there are around two-fold increases in risk of perinatal mortality, low birthweight and preterm birth, about a 50% increase in small for gestational age and a 30-35% increase in birth defects, compared with singletons conceived spontaneously. Couples considering ART should be counselled about the increased risk of adverse outcomes. Epidemiologists, in conjunction with clinical and laboratory colleagues, should now focus on large, methodologically sound studies with long-term follow up that seek to identify the reasons for these increased risks and their long-term consequences, whether they are associated with particular technologies and causes of infertility, and how they might be reduced.

Birth Weight↗

The changing face of surgery: using systematic reviews.

Three systematic reviews relating to pre-admission procedures, admission procedures and staffing policies were undertaken to establish evidence to develop best practice guidelines for day surgery units. Results revealed that a pre-admission intervention can improve patient and surgery outcomes, although the most effective type of intervention should be further investigated. It was also found that distraction can reduce patient preoperative anxiety, and there is no high quality evidence relating skill mix, staffing levels and desired health outcomes in day surgery units. Recommendations for areas of future research are presented.

Ambulatory Surgical Procedures↗

Does updating improve the methodological and reporting quality of systematic reviews?

BACKGROUND: Systematic reviews (SRs) must be of high quality. The purpose of our research was to compare the methodological and reporting quality of original versus updated Cochrane SRs to determine whether updating had improved these two quality dimensions. METHODS: We identified updated Cochrane SRs published in issue 4, 2002 of the Cochrane Library. We assessed the updated and original versions of the SRs using two instruments: the 10 item enhanced Overview Quality Assessment Questionnaire (OQAQ), and an 18-item reporting quality checklist and flow chart based upon the Quality of Reporting of Meta-analyses (QUOROM) statement. At least two reviewers extracted data and assessed quality. We calculated the percentage (with a 95% confidence interval) of 'yes' answers to each question. We calculated mean differences in percentage, 95% confidence intervals and p-values for each of the individual items and the overall methodological quality score of the updated and pre-updated versions using OQAQ. RESULTS: We assessed 53 SRs. There was no significant improvement in the global quality score of the OQAQ (mean difference 0.11 (-0.28; 0.70 p = 0.52)). Updated reviews showed a significant improvement of 18.9 (7.2; 30.6 p < .01) on the OQAQ item assessing whether the conclusions drawn by the author(s) were supported by the data and/or analysis presented in the SR. The QUOROM statement showed that the quality of reporting of Cochrane reviews improved in some areas with updating. Improvements were seen on the items relating to data sources reported in the abstract, with a significant difference of 17.0 (9.8; 28.7 p = 0.01), review methods, reported in the abstract 35 (24.1; 49.1 p = 0.00), searching methods 18.9 (9.7; 31.6 p = 0.01), and data abstraction 18.9 (11.7; 30.9 p = 0.00). CONCLUSION: The overall quality of Cochrane SRs is fair-to-good. Although reporting quality improved on certain individual items there was no overall improvement seen with updating and methodological quality remained unchanged. Further improvement of quality of reporting is possible. There is room for improvement of methodological quality as well. Authors updating reviews should address identified methodological or reporting weaknesses. We recommend to give full attention to both quality domains when updating SRs.

Bibliometrics↗

Meta-review of high-quality systematic reviews of interventions in key areas of liaison psychiatry.

BACKGROUND: When planning and delivering a liaison psychiatry service it is important to have an understanding of the research evidence supporting the use of interventions likely to be delivered by the service. AIMS: To identify high-quality systematic reviews for all interventions in three defined areas of liaison psychiatry, to summarise their clinical implications and to highlight areas where more research is needed. The three areas were the psychological effects of physical illness or treatment, somatoform disorders and self-harming behaviour. METHOD: Computerised database searching, secondary reference searching, hand-searching and expert consultation were used to identify relevant systematic reviews. Studies were reliably selected, and quality-assessed, and data were extracted and interpreted by two reviewers. RESULTS: We found 64 high-quality systematic reviews. Only 14 reviews included meta-analyses. CONCLUSIONS: Many areas of liaison psychiatry practice are not based on high-quality evidence. More research in this area would help inform development and planning of liaison psychiatry services.

Disease↗

Are all antidepressants really the same? The case of fluoxetine: a systematic review.

OBJECTIVE: To systematically review the efficacy and tolerability of fluoxetine, the most widely studied of newer antidepressants, in comparison with all other antidepressants in the acute treatment of depression in patients aged more than 18 years. DATA SOURCES: Studies were identified through electronic searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register and the Cochrane Central Register of Controlled Trials up to March 2004. The terms FLUOXETIN* OR adofen or docutrix or erocap or fluctin or fluctine or fluoxeren or fontex or ladose or lorien or lovan or mutan or prozac or prozyn or reneuron or sanzur or saurat or zactin were used. MEDLINE (1966-2004) and EMBASE (1974-2004) were searched using fluoxetine and randomized controlled trial or random allocation or double-blind method. No language restrictions were applied. Reference lists of relevant papers and previous systematic reviews were hand-searched for published reports up to March 2004. STUDY SELECTION: Only randomized controlled trials (either blind or nonblind) were included. DATA SYNTHESIS: 131 randomized controlled trials were eligible. A p value less than .01 was chosen to test the null hypothesis, and a 99% confidence interval was calculated to detect statistically significant differences with a high degree of confidence. Fixed- and random-effects relative risks, odds ratios (ORs), and Peto ORs were routinely calculated for each outcome measure. In terms of efficacy, we found a statistically significant difference favoring sertraline and venlafaxine over fluoxetine. In terms of tolerability, patients allocated to fluoxetine were less likely to leave the study early only in comparison with those allocated to amitriptyline and pramipexole. CONCLUSIONS: This systematic review highlighted that there are differences between fluoxetine and specific comparator antidepressants. Several of the differences met a prespecified criterion for clinical significance. The statistical approach adopted in this systematic review could represent a useful tool for putting clinical trial data into practice.

Adult↗