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PubMed2004

Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis.

BACKGROUND AND PURPOSE: Previously published meta-analyses exploring the effect of statins on stroke incidence included 20,000 patients and found a 2% to 30% risk reduction. It is not clear whether this is attributable to low-density lipoprotein-cholesterol (LDL-C) reduction. Statin trials have now included >90,000 patients. We have determined the effect of statins and LDL-C reduction on stroke prevention. SUMMARY OF REVIEW: We performed a systematic review and meta-analysis of all randomized trials testing statin drugs published before August 2003. The trials were identified using a computerized PubMed search. We analyzed separately statin effect on incident strokes and on carotid intima-media thickness (IMT) according to LDL-C reduction. The relative risk reduction for stroke was 21% (odds ratio [OR], 0.79 [0.73 to 0.85]), with no heterogeneity between trials. Fatal strokes were reduced but not significantly: by 9% (OR, 0.91 [0.76 to 1.10]). There was no increase in hemorrhagic strokes (OR, 0.90 [0.65 to 1.22]). Statin size effect was closely associated with LDL-C reduction. Each 10% reduction in LDL-C was estimated to reduce the risk of all strokes by 15.6% (95% CI, 6.7 to 23.6) and carotid IMT by 0.73% per year (95% CI, 0.27 to 1.19). CONCLUSIONS: Statins may reduce the incidence of all strokes without any increase in hemorrhagic strokes, and this effect is mainly driven by the extent of between-group LDL-C reduction. Carotid IMT progression also strongly correlated with LDL-C reduction.

Carotid Artery Diseases↗

PubMed2005

True incisor intrusion attained during orthodontic treatment: a systematic review and meta-analysis.

INTRODUCTION: The purpose of this meta-analysis was to quantify the amount of true incisor intrusion attained during orthodontic treatment. METHODS: Electronic databases (PubMed, Medline, Medline In-Process & Other Non-Indexed Citations, all EBM reviews [Cochrane Database of Systematic Reviews, ASP Journal Club, DARE, and CCTR], Embase, Web of Science, and Lilacs) were searched with the help of a senior health sciences librarian. The goal was to identify clinical trials that assessed true incisor intrusion through cephalometric analysis and factored out craniofacial growth when required. From the selected abstracts, original articles were retrieved, and their references were hand searched for missing articles. RESULTS: Twenty-eight articles met the initial inclusion criteria, but 24 were rejected because they did not quantify true incisor intrusion or factor out normal growth impact when required. The remaining 4 articles showed that true incisor intrusion is attainable (0.26 to 1.88 mm for the maxillary incisors and -0.19 to 2.84 mm for the mandibular incisors) but with large variability depending on the appliance used. A meta-analysis with results from the 2 articles that used the segmental technique was completed. The combined mean estimates of intrusion and 95% CI were 1.46 mm (1.05-1.86 mm) for the maxillary incisors and 1.90 mm (1.22-2.57 mm) for the mandibular incisors. CONCLUSIONS: True incisor intrusion is achievable in both arches, but the clinical significance of the magnitude of true intrusion as the sole treatment option is questionable for patients with severe deepbite. In nongrowing patients, the segmented arch technique can produce 1.5 mm of incisor intrusion in the maxillary arch and 1.9 mm in the mandibular arch.

Cephalometry↗

PubMed2003

Blood pressure reduction and secondary prevention of stroke and other vascular events: a systematic review.

BACKGROUND: High blood pressure is a risk factor for stroke recurrence. We assessed the effectiveness of lowering blood pressure in preventing recurrent vascular events in patients with previous stroke or transient ischemic attack. SUMMARY OF REVIEW: We performed a systematic review and meta-regression of completed randomized controlled trials that investigated the effect of lowering blood pressure on recurrent vascular events in patients with prior ischemic or hemorrhagic stroke or transient ischemic attack. Trials were identified from searches of 3 electronic databases (Cochrane Library, EMBASE, MEDLINE). Seven randomized controlled trials, with 8 comparison groups, were included. Lowering blood pressure or treating hypertension with a variety of antihypertensive agents reduced stroke (odds ratio [OR], 0.76; 95% CI, 0.63 to 0.92), nonfatal stroke (OR, 0.79; 95% CI, 0.65 to 0.95), myocardial infarction (OR, 0.79; 95% CI, 0.63 to 0.98), and total vascular events (OR, 0.79; 95% CI, 0.66 to 0.95). No effect was seen on vascular or all-cause mortality. Heterogeneity was present for several outcomes and was partly related to the class of antihypertensive drugs used; angiotensin-converting enzyme inhibitors and diuretics separately, and especially together, reduced vascular events, while beta-receptor antagonists had no discernable effect. The reduction in stroke was related to the difference in systolic blood pressure between treatment and control groups (P=0.002). CONCLUSIONS: Evidence from randomized controlled trials supports the use of antihypertensive agents in lowering blood pressure for the prevention of vascular events in patients with previous stroke or transient ischemic attack. Vascular prevention is associated positively with the magnitude by which blood pressure is reduced.

Antihypertensive Agents↗

PubMed2006

The clinical effectiveness and cost-effectiveness of newer drugs for children with epilepsy. A systematic review.

OBJECTIVES: To examine the clinical effectiveness and cost-effectiveness of newer antiepileptic drugs (AEDs) for epilepsy in children: gabapentin, lamotrigine, levetiracetam, oxcarbazepine, tiagabine, topiramate and vigabatrin. DATA SOURCES: Electronic databases. Drug company submissions. REVIEW METHODS: For the systematic review of clinical and cost-effectiveness, studies were assessed for inclusion according to predefined criteria. Data extraction and quality assessment were also undertaken. A decision-analytic model was constructed to estimate the cost-effectiveness of the newer agents in children with partial seizures, the only condition where there were sufficient trial data to inform a model. RESULTS: The quality of the randomised controlled trial (RCT) data was generally poor. For each of the epilepsy subtypes considered in RCTs identified for this review (partial epilepsy with or without secondary generalisation, Lennox-Gastaut syndrome, infantile spasms, absence epilepsy and benign epilepsy with centrotemporal spikes), there is some evidence from placebo-controlled trials that the newer agents tested are of some value in the treatment of these conditions. Where active controls have been used, the limited evidence available does not indicate a difference in effectiveness between newer and older drugs. The data are not sufficient to inform a prescribing strategy for any of the newer agents in any of these conditions. In particular, there is no clinical evidence to suggest that the newer agents should be considered as a first-choice treatment in any form of epilepsy in children. Annual drug costs of the newer agents ranges from around 400 pound to 1200 pound, depending on age and concomitant medications. An AED that is ineffective or has intolerable side-effects will only be used for a short period of time, and many patients achieving seizure freedom will successfully withdraw from drug treatment without relapsing. The results of the decision-analytic model do not suggest that the use of the newer agents in any of the scenarios considered is clearly cost-effective but, similarly, do not indicate that they are clearly not cost-effective. CONCLUSIONS: The prognosis for children diagnosed with epilepsy is generally good, with a large proportion responding well to the first treatment given. A substantial proportion, however, will not respond well to treatment, and for these patients the clinical goal is to find an optimal balance between the benefits and side-effects of any treatment given. For the newly, or recently, diagnosed population, the key question for the newer drugs is how soon they should be tried. The cost-effectiveness of using these agents early, in place of one of the older agents, will depend on the effectiveness and tolerability of these agents compared with the older agents; the evidence from the available trial data so far suggests that the newer agents are no more effective but may be somewhat better tolerated than the older agents, and so the cost-effectiveness for early use will depend on the trade-off between effectiveness and tolerability, both in terms of overall (long-term) treatment retention and overall utility associated with effects on seizure rate and side-effects. There are insufficient data available to estimate accurately the nature of this trade off either in terms of long-term treatment retention or utility. Better information is required from RCTs before any rational evidence-based prescribing strategy could be developed. Ideally, RCTs should be conducted from a 'public health' perspective, making relevant comparisons and incorporating outcomes of interest to clinicians and patients, with sufficiently long-term follow-up to determine reliably the clinical utility of different treatments, particularly with respect to treatment retention and the balance between effectiveness and tolerability. RCTs should mirror clinical practice with respect to diagnosis, focusing on defined syndromes or, where no syndrome is identified, on groups defined by specific seizure type(s) and aetiology. Epilepsy in children is a complex disease, with a variety of distinct syndromes and many alternative treatment options and outcomes. Diagnosis-specific decision-analytic models are required; further research may be required to inform parameter values adequately with respect to epidemiology and clinical practice.

Anticonvulsants↗

PubMed2004

A systematic review of intraoperative radiotherapy in early breast cancer.

A systematic review was undertaken to assess the safety and efficacy of intraoperative radiotherapy (IORT) in early breast cancer compared with breast conserving surgery with postoperative radiotherapy. Literature databases were searched up to March 2002 inclusive. IORT studies of any design and breast conserving therapy randomised controlled trials with sample sizes greater than 500 patients (with at least one arm of breast conserving therapy (BCT)) and systematic reviews on BCT published since 1992, were included for comparison. Seven unique IORT studies were located; one randomised controlled trial, one study with a concurrent control group and five case series. Minor postoperative complications were reported following IORT. Short-term results were similar for both treatment modalities in terms of local recurrence, disease-free and overall survival. However, the current evidence base is poor, making definitive assessment on IORT very difficult. Further research is required to clarify several issues such as identification of the most appropriate subgroups of patients for IORT, a comparison of the currently available mobile IORT technologies, establishing whether IORT is most appropriate as a boost replacement dose or replacement for all postoperative radiotherapy, the examination of how biological repair processes may differ between the two treatment modalities and determining precisely where local recurrences originate with respect to the original tumour site.

Breast Neoplasms↗

PubMed2007

Worked examples of alternative methods for the synthesis of qualitative and quantitative research in systematic reviews.

BACKGROUND: The inclusion of qualitative studies in systematic reviews poses methodological challenges. This paper presents worked examples of two methods of data synthesis (textual narrative and thematic), used in relation to one review, with the aim of enabling researchers to consider the strength of different approaches. METHODS: A systematic review of lay perspectives of infant size and growth was conducted, locating 19 studies (including both qualitative and quantitative). The data extracted from these were synthesised using both a textual narrative and a thematic synthesis. RESULTS: The processes of both methods are presented, showing a stepwise progression to the final synthesis. Both methods led us to similar conclusions about lay views toward infant size and growth. Differences between methods lie in the way they dealt with study quality and heterogeneity. CONCLUSION: On the basis of the work reported here, we consider textual narrative and thematic synthesis have strengths and weaknesses in relation to different research questions. Thematic synthesis holds most potential for hypothesis generation, but may obscure heterogeneity and quality appraisal. Textual narrative synthesis is better able to describe the scope of existing research and account for the strength of evidence, but is less good at identifying commonality.

Growth↗

PubMed2000

Measuring appropriate use of acute beds. A systematic review of methods and results.

A systematic review of the methods used to assess appropriateness of acute bed use and the evidence on the scale of inappropriate use in different patient groups is presented. Issues of generalisability of the findings are also addressed. Criteria based tools are the accepted way of measuring inappropriate days of stay and admissions, although opinion based classification is very common. While a number of tools exist, few have been adequately tested for reliability and validity. The Appropriateness Evaluation Protocol (AEP) is the most commonly used tool, and has been tested more widely. It appears to be both reliable and valid. An estimated 29% of admissions to acute psychiatric may be inappropriate. Regarding days of care after admission, between 24 and 58% of stays were not judged to be appropriate for continued stay on an acute ward. The need for continued acute psychiatric care may become lower as patients experience continued stay in the acute setting. A lack of housing and community support was the most commonly cited reason preventing discharge. Rates of inappropriate use appear to be higher for older patients than for the general population. Wide variation in rates of inappropriate days of stay was found, but it may be safe to assume that inappropriate use is greater than 20% across a wide variety of settings. Reasons for older patients to remain in an acute hospital bed after medically necessary are typically moderate nursing care needs (i.e. long-term care). The estimates of inappropriate use in other groups was found to be highly variable. Before definitive conclusions on the inappropriate use of acute beds can be made, future research needs to take into account the methodological problems discussed here.

Acute Disease↗

PubMed2004

Systematic review of the long-term effects and economic consequences of treatments for obesity and implications for health improvement.

OBJECTIVES: To undertake a systematic review of the long-term effects of obesity treatments on body weight, risk factors for disease, and disease. METHODS: The study encompassed three systematic reviews that examined different aspects of obesity treatments. (1) A systematic review of obesity treatments in adults where the methods of the Cochrane Collaboration were applied and randomised controlled trials (RCTs) with a follow-up of at least 1 year were evaluated. (2) A systematic epidemiological review, where studies were sought on long-term effects of weight loss on morbidity and/or mortality, and examined through epidemiological modelling. (3) A systematic economic review that sought reports with both costs and outcomes of treatment, including recent reports that assessed the cost-effectiveness of pharmaceutical and surgical interventions. A Markov model was also adopted to examine the cost-effectiveness of a low-fat diet and exercise intervention in adults with obesity and impaired glucose tolerance. RESULTS: The addition of the drugs orlistat or sibutramine was associated with weight loss and generally improved risk factors, apart from diastolic blood pressure for sibutramine. Metformin was associated with decreased mortality after 10 years in obese people with type 2 diabetes. Low-fat diets were associated with continuing weight loss for 3 years and improvements in risk factors, as well as prevention of type 2 diabetes and improved control of hypertension. Insufficient evidence was available to demonstrate the benefits of low calorie or very low calorie diets. The addition of an exercise or behaviour programme to diet was associated with improved weight loss and risk factors for at least 1 year. Studies combining low-fat diets, exercise and behaviour therapy suggested improved hypertension and cardiovascular disease. Family therapy was associated with improved weight loss for 2 years compared to individual therapy. There was insufficient evidence to conclude that individual therapy was more beneficial than group therapy. Weight lost more quickly (within 1 year), from the epidemiology review, may be more beneficial with respect to the risk of mortality. The effects of intentional weight loss need further investigation. Weight loss from surgical and non-surgical interventions for people suffering from obesity was associated with decreased risk of development of diabetes, and a reduction in low-density lipoprotein cholesterol, total cholesterol and blood pressure, in the long term. Targeting high-risk individuals with drugs or surgery was likely to result in a cost per additional life-year or quality-adjusted life-year (QALY) of no more than 13,000 British pounds. There was also suggestive evidence of cost saving from treatment of people with type 2 diabetes with metformin. Targeting surgery on people with severe obesity and impaired glucose tolerance was likely to be more cost-effective at 2329 British pounds per additional life-year. Economic modelling over 6 years for diet and exercise for people with impaired glucose tolerance was associated with a high initial cost per additional QALY, but by the sixth year the cost per QALY was 13,389 British pounds. Results did not include cost savings from diseases other than diabetes, and therefore may be conservative. CONCLUSIONS: The drugs orlistat and sibutramine appear beneficial for the treatment of adults with obesity, and metformin for obese patients with type 2 diabetes. Exercise and/or behaviour therapy appear to improve weight loss when added to diet. Low-fat diets with exercise, or with exercise and behaviour therapy are associated with the prevention of type 2 diabetes and hypertension. Long-term weight loss in epidemiological studies was associated with reduced risk of type 2 diabetes, and may be beneficial for cardiovascular disease. Low-fat diets and exercise interventions in individuals at risk of obesity-related illness are of comparable cost to drug treatments. Long-term pragmatic RCTs of obesity treatments in populations with obesity-related illness or at high risk of developing such illness are needed (to include an evaluation of risk factors, morbidity, quality of life and economic evaluations). Drug trials that include dietary advice, plus exercise and/or behaviour therapy are also needed. Research exploring effective types of exercise, diet or behaviour and also interventions to prevent obesity in adults is required.

Anti-Obesity Agents↗

PubMed2006

Pennsaid therapy for osteoarthritis of the knee: a systematic review and metaanalysis of randomized controlled trials.

OBJECTIVE: To systematically review published randomized controlled trials (RCT) evaluating a new topical diclofenac solution (Pennsaid) in patients with osteoarthritis (OA) of the knee. METHODS: RCT were identified by searching electronic data sources as well as by contact with the manufacturer of Pennsaid. Details of study demographics, methodology, quality, and outcomes were analyzed. A metaanalysis evaluating the efficacy and safety of Pennsaid in OA of the knee was performed. RESULTS: Four RCT were analyzed in this systematic review (3 published reports and one published abstract). Mean trial duration was 8.5 weeks. Generally, these RCT were of excellent quality. The mean Jadad quality score was 4.5 out of 5. Many indicators of high quality in a RCT were found in these RCT, including adequate descriptions of the methods used for randomization, blinding, and allocation concealment. In comparison to a vehicle control placebo (VCP), the standardized mean differences (SMD) for the WOMAC pain, stiffness, and physical function subscales, as well as for patient global assessment, were all statistically significant in favor of Pennsaid, with SMD ranging from 0.30 to 0.39. Pennsaid was as safe as VCP, with the only exception that it was more likely to result in minor skin dryness at the site of application (relative risk 1.7). In a 12 week equivalence trial that used the WOMAC subscales to compare treatment response, Pennsaid was as effective as oral diclofenac, but was much better tolerated. CONCLUSION: Pennsaid is an effective topical NSAID in patients with OA of the knee. Apart from minor localized skin reactions, Pennsaid was as safe as VCP. It is not known whether the favorable results of Pennsaid can be extrapolated to other topical NSAID preparations. Pennsaid deserves further consideration when the existing treatment guidelines for OA of the knee are updated.

Administration, Topical↗

PubMed2006

Course of functional status and pain in osteoarthritis of the hip or knee: a systematic review of the literature.

OBJECTIVE: To systematically review studies describing the course of functioning in patients with osteoarthritis (OA) of the hip or knee and identifying potential prognostic factors. METHODS: A systematic search was performed. Studies involving patients with hip or knee OA, >6 months of followup, and outcome measures on functional status or pain were included. Methodologic quality was assessed using a standardized set of 11 criteria; a qualitative data analysis was performed. RESULTS: Approximately 6,500 titles and abstracts were screened and 48 publications were considered for inclusion. Eighteen studies, 4 of which met the high methodologic quality criteria, were included. For hip OA, there was limited evidence that functional status and pain do not change during the first 3 years of followup. After 3 years, however, a worsening of functional status and pain was seen. For knee OA, there was conflicting evidence for the first 3 years and limited evidence for worsening of pain and functional status after 3 years. Furthermore, limited evidence was established for negative associations between future functional status and laxity, proprioceptive inaccuracy, age, body mass index, and knee pain intensity. In contrast, greater muscle strength, better mental health, better self-efficacy, social support, and more aerobic exercise were protective factors in the first 3 years. CONCLUSION: Pain and functional status in hip or knee OA seem to deteriorate slowly, with limited evidence for worsening after 3 years of followup. In specific subgroups, prognosis in the first 3 years of followup was either worse or better, as both risk factors and protective factors were identified. Prognostic factors included biomechanical factors, psychological factors, clinical factors, and treatment modalities. To strengthen the evidence, further high-quality longitudinal research on hip or knee OA functioning is needed.

Disease Progression↗

PubMed2026

Views and Experiences of People With Dementia, Informal Caregivers and Professionals on Eating and Drinking Difficulties: A Qualitative Systematic Review.

AIM: This study aims to explore the views and experiences of people with dementia, informal caregivers and professionals regarding eating and drinking difficulties. DESIGN: A qualitative systematic review was conducted. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis guidelines were used to conduct this systematic review. The quality of the included studies was assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research, and the data were thematically synthesised using Thomas and Harden's three-stage method. DATA SOURCES: Six electronic databases (PubMed, EMBASE, Cochrane Library, Web of Science, CINAHL and PsycINFO) were searched from their respective inception dates to August 2025 to identify relevant studies. RESULTS: Thematic analysis of the 16 included studies identified four key themes: (1) Physiological and psychological changes in people with dementia and caregivers; (2) factors influencing eating and drinking in people with dementia; (3) needs and recommendations for people with dementia, informal caregivers and professionals; (4) selection of eating methods for end-stage people with dementia. CONCLUSIONS: Eating and drinking difficulties affect the well-being of both patients and caregivers. A good dining environment improves mealtime pleasure but demands caregivers' time and energy. All parties emphasised the importance of effective communication. In end-stage dementia, professional assistance is crucial for enteral nutrition decisions. IMPLICATIONS FOR THE PROFESSION AND/OR PATIENT CARE: Collaboration among patients, caregivers and professionals is vital for creating tailored nutritional plans and improving mealtime environments, thereby enhancing nutritional intake. In advanced dementia, providers must provide balanced information on comfort feeding versus enteral nutrition to aid decision-making. IMPACT: What problems were addressed in this study? This study addressed the lack of a consolidated, tri-perspective understanding of eating and drinking difficulties in dementia care settings. What are the main findings? Four key themes were identified: physiological and psychological changes, influencing factors, stakeholder needs and end-of-life decision-making. Where and on whom will the research have an impact? This will impact care practices for people with dementia and inform the training and support of informal caregivers and healthcare professionals.

Humans↗

PubMed2005

A systematic review finds that diagnostic reviews fail to incorporate quality despite available tools.

BACKGROUND AND OBJECTIVE: To review existing quality assessment tools for diagnostic accuracy studies and to examine to what extent quality was assessed and incorporated in diagnostic systematic reviews. METHODS: Electronic databases were searched for tools to assess the quality of studies of diagnostic accuracy or guides for conducting, reporting or interpreting such studies. The Database of Abstracts of Reviews of Effects (DARE; 1995-2001) was used to identify systematic reviews of diagnostic studies to examine the practice of quality assessment of primary studies. RESULTS: Ninety-one quality assessment tools were identified. Only two provided details of tool development, and only a small proportion provided any indication of the aspects of quality they aimed to assess. None of the tools had been systematically evaluated. We identified 114 systematic reviews, of which 58 (51%) had performed an explicit quality assessment and were further examined. The majority of reviews used more than one method of incorporating quality. CONCLUSION: Most tools to assess the quality of diagnostic accuracy studies do not start from a well-defined definition of quality. None has been systematically evaluated. The majority of existing systematic reviews fail to take differences in quality into account. Reviewers should consider quality as a possible source of heterogeneity.

Bias↗

PubMed1997

Selecting and appraising studies for a systematic review.

After thoroughly searching the potentially relevant literature for a systematic review, reviewers face the sequential tasks of selecting studies for inclusion and appraising these studies. Methodical, impartial, and reliable strategies are necessary for these two tasks because systematic reviews are retrospective exercises and are therefore prone to both bias and random error. To plan for study selection, reviewers begin with a focused clinical question and choose selection criteria that reflect this question. A detailed selection protocol that specifies the study designs and publication status of articles to be included is often helpful. Selection criteria are itemized on customized forms and are used to examine each potentially relevant primary study, usually by two different reviewers. In planning the critical appraisal of included studies, reviewers decide which clinical and methodologic study features require documentation. After choosing methods for evaluating study quality, reviewers construct customized appraisal forms and an explicit protocol for the actual evaluation. Some of the techniques commonly used to minimize the potential for error in study appraisal include duplicate, independent examination; blinding to study results and other identifying features of each article; and correspondence with study authors to clarify issues. Ultimately, primary studies should be selected, appraised, and reported in sufficient detail to allow readers to judge the applicability of the review to clinical practice and to clarify the strength of the inferences that can be drawn from the review.

Research Design↗

PubMed2003

Rural doctors and rural backgrounds: how strong is the evidence? A systematic review.

OBJECTIVE: We sought to summarise the evidence for an association between rural background and rural practice by systematically reviewing the national and international published reports. DESIGN: A systematic review. SETTING: A search of the national and international published reports from 1973 to October 2001. SUBJECT: The search criteria included observational studies of a case-control or cohort design making a clear and quantitative comparison between current rural and urban doctors, this resulted in the identification of 141 studies for potential inclusion. RESULTS: We systematically reviewed 12 studies. Rural background was associated with rural practice in 10 of the 12 studies, in which it was reported, with most odds ratios (OR) approximately 2-2.5. Rural schooling was associated with rural practice in all 5 studies that reported on it, with most OR approximately 2.0. Having a rural partner was associated with rural practice in 3 of the 4 studies reporting on it, with OR approximately 3.0. Rural undergraduate training was associated with rural practice in 4 of 5 studies, with most OR approximately 2.0. Rural postgraduate training was associated with rural practice in 1 of 2 studies, with rural doctors reporting rural training about 2.5 times more often. CONCLUSIONS: There is consistent evidence that the likelihood of working in rural practice is approximately twice greater among doctors with a rural background. There is a smaller body of evidence in support of the other rural factors studied, and the strength of association is similar to that for rural background.

Attitude of Health Personnel↗

PubMed2005

Continuous versus intermittent intravenous administration of antibacterials with time-dependent action: a systematic review of pharmacokinetic and pharmacodynamic parameters.

We performed a systematic review of randomised clinical trials to evaluate the comparative pharmacokinetic and pharmacodynamic properties of the continuous versus intermittent mode of intravenous administration of various antibacterials. Data were identified from PubMed (January 1950 to January 2005), Current Contents, the Cochrane central register of controlled trials, and references from relevant articles and reviews. Seventeen randomised clinical trials comparing continuous with intermittent intravenous administration of the same antibacterial regimen and examining the pharmacokinetic and pharmacodynamic properties were included in this systematic review. We reviewed data regarding the clinical setting, number of participants, antibacterial agents and dosages used, as well as maximum serum concentration (Cmax), trough serum concentration (Cmin), steady-state or plateau serum concentration (Css), area under the concentration-time curve (AUC), time above the minimum inhibitory concentration (MIC) [T>MIC], AUC: MIC, elimination rate constant, elimination half-life, volume of distribution and systematic clearance. The mean Cmax of the intermittently administered antibacterials was higher compared with Css achieved by the continuous infusion of the same antibacterial in all eligible studies (Cmax was on average 5.5 times higher than Css, range 1.9-11.2). Css was on average 5.8 times higher than the Cmin of the intermittently administered antibacterials (range 1.2-15.6). In three of six studies the length of time that the drug concentration was above the MIC of the responsible pathogens was longer in patients receiving the antibacterials continuously. In conclusion, the reviewed data suggest that the continuous intravenous infusion of antibacterials with time-dependent bacterial killing seems to be superior than the intermittent intravenous administration, from a pharmacodynamic point of view, at least when treating bacteria with high MIC values for the studied antibacterials.

Animals↗

PubMed2005

Complementary therapies for reducing body weight: a systematic review.

The prevalence of obesity is increasing at an alarming rate and a plethora of complementary therapies are on offer claiming effectiveness for reducing body weight. The aim of this systematic review is to critically assess the evidence from randomized controlled trials (RCTs) and systematic reviews of complementary therapies for reducing body weight. Literature searches were conducted on Medline, Embase, Amed, and the Cochrane Library until January 2004. Hand-searches of relevant medical journals and bibliographies of identified articles were conducted. There were no restrictions regarding the language of publication. Trial selection, quality assessment and data abstraction were performed systematically and independently by two authors. Data from RCTs and systematic reviews, which based their findings on the results of RCTs, were included. Six systematic reviews and 25 additional RCTs met our inclusion criteria and were reviewed. The evidence related to acupuncture, acupressure, dietary supplements, homeopathy and hypnotherapy. Except for hypnotherapy, Ephedra sinica and other ephedrine-containing dietary supplements the weight of the evidence is not convincing enough to suggest effectiveness. For these interventions, small effects compared with placebo were identified. In conclusion, our findings suggest that for most complementary therapies, the weight of the evidence for reducing body is not convincing. Hypnotherapy, E. sinica and other ephedrine-containing dietary supplements may lead to small reductions in body weight. However, the intake of E. sinica and ephedrine is associated with an increased risk of adverse events. Interventions suggesting positive effects in single RCTs require independent replication.

Acupuncture Therapy↗

PubMed2026

Complication rates of 16- and 18-gauge needles for native kidney biopsies: a systematic review and proportional meta-analysis.

This systematic review and meta-analysis evaluated complication rates and diagnostic yield reported in studies of adult native kidney biopsy using 16-gauge (16 G) or 18-gauge (18 G) needles. We included randomized trials and cohort studies of real-time ultrasound-guided biopsies, including case series. MEDLINE, Embase, and CENTRAL were searched through October 2024. Two reviewers independently performed study selection, data extraction, and risk of bias assessment using Joanna Briggs Institute tools. Random-effects meta-analyses estimated pooled proportions with 95% confidence intervals (CI), and univariable random-effects meta-regression explored study-level associations with major complications, transfusion, or gross hematuria. We screened 4,499 titles and abstracts and reviewed 319 full-text articles; 62 studies comprising 68 biopsy series were included. The pooled major complication rate in studies using 16 G needles was 1.83% (95% CI: 1.20-2.79) and 1.29% (95% CI: 0.78-2.13) in studies using 18 G needles, with no statistically significant difference. Mean glomerular yield was 18.8 with 16 G and 17.5 with 18 G needles. In study-level meta-regression, studies with higher prevalence of acute kidney injury, lower mean estimated glomerular filtration rate, or lower mean hemoglobin reported higher pooled complication rates. Most studies were single-arm cohorts; between-needle differences therefore reflect indirect study-level contrasts. Interpretation is limited by retrospective design and heterogeneity across studies. Overall, studies using both needle sizes reported low complication rates and similar diagnostic yield, although definitions and reporting varied. Direct comparative studies are needed to determine whether meaningful differences exist.

Humans↗

PubMed2026

Nonoperative Management is Associated With Similar Long-Term Patient-Reported Outcomes Compared With Surgery for Cervical Radiculopathy: A Systematic Review and Meta-analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVE: To compare long-term patient-reported outcomes between surgical and nonoperative management for cervical radiculopathy. SUMMARY OF BACKGROUND DATA: Cervical radiculopathy is a common condition associated with substantial morbidity. While both surgical and nonoperative approaches are effective, it remains unclear which patients benefit most from each strategy and whether earlier operative intervention confers meaningful long-term advantage. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane Library were searched from inception to January 2026 for randomized and observational studies comparing surgical and nonoperative management for cervical radiculopathy. Primary outcomes included visual analog scale (VAS) scores for neck and arm pain, neck disability index (NDI), and overall clinical success. Secondary outcomes included analgesia use and sick leave. Random-effects meta-analyses were performed using restricted maximum likelihood estimation. Risk of bias was assessed using RoB 2 and ROBINS-I, and certainty of evidence using GRADE. RESULTS: Eleven studies comprising 1154 patients (surgical: 522; nonoperative: 632) were included. Surgery was not associated with superior outcomes in VAS for arm pain (MD: -0.67, 95% CI: -1.59 to 0.26, P =0.12), VAS for neck pain (MD: -0.50, 95% CI: -1.38 to 0.38; P =0.19), or NDI (MD: -3.69, 95% CI: -9.63 to 2.25, P =0.16) after 12 months of treatment, nor in overall success (RR: 1.11, 95% CI: 0.93-1.34, P =0.21). No significant differences were observed in analgesia use ( P =0.54) or sick leave ( P =0.48) at last follow-up. Most studies were rated serious risk of bias and overall certainty of evidence was moderate. CONCLUSION: Evidence from this pooled analysis suggests that long-term pain, disability, and functional outcomes are comparable between patients selected for nonoperative management and those selected for surgery. These findings reflect outcomes within selected cohorts and should not be interpreted as evidence of therapeutic equivalence. LEVEL OF EVIDENCE: Level II.

Humans↗