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The effectiveness of primary care-based interventions to promote breastfeeding: systematic evidence review and meta-analysis for the US Preventive Services Task Force.

PURPOSE: We wanted to systematically review whether primary care-based interventions improve initiation and duration of breastfeeding. METHODS: Studies were found by searching MEDLINE (1966-2001), Health-STAR, the Cochrane Database of Systematic Reviews, the National Health Service Centre for Reviews and Dissemination Databases, and bibliographies of identified trials and review articles. Studies were included if they originated in the primary care setting and were conducted in a developed country, written in English, and contained a concurrent control group. RESULTS: Thirty randomized and nonrandomized controlled trials and 5 systematic reviews of breastfeeding counseling were included. Educational programs had the greatest effect of any single intervention on both initiation (difference 0.23; 95% confidence interval [CI], 0.12-0.34) and short-term duration (difference 0.39; 95% CI, 0.27-0.50). Support programs conducted by telephone, in person, or both increased short-term (difference 0.11; 95% CI, 0.03-0.19) and long-term duration (difference 0.08; 95% CI, 0.02-0.16). In contrast, written materials such as pamphlets did not significantly increase breastfeeding. Data were insufficient to determine whether the combination of education with support was more effective than education alone. CONCLUSIONS: Educational programs were the most effective single intervention. One woman would breast-feed for up to 3 months for every 3 to 5 women attending breastfeeding educational programs. Future research and policy should focus on translating these findings into more widespread practice in diverse primary care settings.

Advisory Committees↗

The effect of antiretroviral therapy adherence on viral load suppression rate among people living with HIV in Ethiopia: A systematic review and meta-analysis.

BACKGROUND: Antiretroviral therapy (ART) adherence is a key determinant of viral load suppression among people living with HIV (PLHIV). In Ethiopia, evidence on the magnitude of ART adherence and its effect on virological outcomes remains fragmented. This systematic review and meta-analysis aimed to estimate the pooled prevalence of ART adherence and viral load suppression, and to measure the association between adherence and viral suppression among PLHIV in Ethiopia. METHODS: This systematic review and meta-analysis used the PRISMA checklist for systematic reviews and meta-analyses. The review protocol has been registered onPROSPERO:(CRD420251125899). PubMed, ScienceDirect, Scopus, Epistemonikos, and Google Scholar were searched. The quality of included articles has been evaluated with a Newcastle-Ottawa Scale (NOS), adapted for observational studies. A random-effects model using restricted maximum likelihood (REML) with Knapp-Hartung adjustment was used to estimate pooled prevalence and odds ratio. Heterogeneity was assessed using I2, τ2, and Cochran's Q test. RESULTS: A total of 39 studies were included in the final analysis. The pooled prevalence of good ART adherence was 79.4% (95% CI: 74.8%-83.4%), while the pooled viral load suppression rate was 77.5% (95% CI: 72.5%-81.8%). The pooled odds ratio showed that good ART adherence was strongly associated with viral load suppression (OR = 6.30, 95% CI: 4.84-8.19). Substantial heterogeneity was observed across studies for both adherence and viral suppression outcomes (I2 > 90%). CONCLUSIONS: ART adherence and viral load suppression among PLHIV in Ethiopia are relatively high but remain below global targets. Good adherence was significantly associated with virologic suppression, highlighting adherence as a critical modifiable factor for achieving optimal treatment outcomes. Strengthening adherence support interventions is essential to improve virological success and advance progress toward HIV epidemic control.

Humans↗

Immediate angioplasty after thrombolysis: a systematic review.

BACKGROUND: The role of immediate transfer for percutaneous coronary intervention (PCI) after thrombolysis for ST-segment elevation myocardial infarction remains controversial. We performed a systematic review of the related literature to determine whether thrombolysis followed by transfer for immediate or early PCI is safe, feasible and superior to conservative management. METHODS: A systematic literature search of MEDLINE, EMBASE, the Cochrane Database for Systematic Reviews and Cochrane Central Register of Controlled Trials, and the American Heart Association EndNote 7 Master Library databases, was performed to 2004 for relevant published studies. The level of evidence and the quality of the study design and methods were rated by 2 reviewers according to a standardized classification. A quantitative meta-analysis was performed to assess the effect at 6-12 months on mortality of immediate or early PCI after thrombolysis. RESULTS: We found 13 articles that were supportive of immediate or early PCI after thrombolysis and 16 that were neutral or provided evidence opposing it. The largest randomized trials and meta-analyses showed no benefit of routine PCI immediately or shortly after thrombolysis. The studies that were supportive were generally more recent and more frequently involved coronary stents. One large trial supported early PCI after thrombolysis for patients with myocardial infarction complicated by cardiogenic shock. Overall, the difference in mortality rates between the invasive strategy and conservative care was nonsignificant. The 3 stent-era trials showed a significantly lower mortality among patients randomly assigned to the invasive strategy (5.8% v. 10.0%, odds ratio 0.55, 95% confidence interval 0.32-0.92). Analysis of variance found a significant difference in treatment effect between stent-era and pre-stent-era trials. INTERPRETATION: At present, there is inadequate evidence to recommend routine transfer of patients for immediate or early PCI after successful thrombolysis. Results of recent trials using contemporary PCI techniques, including coronary stents, appear more favourable but need to be confirmed in large randomized trials, which are currently in progress. Transfer for immediate PCI is recommended for patients with cardiogenic shock, hemodynamic instability or persistent ischemic symptoms after thrombolysis.

Angioplasty, Balloon, Coronary↗

[Systematic review: a resource that allows for the incorporation of evidence into nursing practice].

Systematic review is an important resource in evidence-based practice, which consists in a form of synthesizing the research results related to a specific problem. This article aimed to offer subsidies for reflections with a view to the construction and/or application of systematic reviews in the nursing environment. Based on the literature, authors presented the phases comprising a systematic review and the relevant aspects that must be considered for using this resource.

Evidence-Based Medicine↗

Effectiveness of acupuncture in veterinary medicine: systematic review.

Acupuncture is a popular complementary treatment option in human medicine. Increasingly, owners also seek acupuncture for their animals. The aim of the systematic review reported here was to summarize and assess the clinical evidence for or against the effectiveness of acupuncture in veterinary medicine. Systematic searches were conducted on Medline, Embase, Amed, Cinahl, Japana Centra Revuo Medicina and Chikusan Bunken Kensaku. Hand-searches included conference proceedings, bibliographies, and contact with experts and veterinary acupuncture associations. There were no restrictions regarding the language of publication. All controlled clinical trials testing acupuncture in any condition of domestic animals were included. Studies using laboratory animals were excluded. Titles and abstracts of identified articles were read, and hard copies were obtained. Inclusion and exclusion of studies, data extraction, and validation were performed independently by two reviewers. Methodologic quality was evaluated by means of the Jadad score. Fourteen randomized controlled trials and 17 nonrandomized controlled trials met our criteria and were, therefore, included. The methodologic quality of these trials was variable but, on average, was low. For cutaneous pain and diarrhea, encouraging evidence exists that warrants further investigation in rigorous trials. Single studies reported some positive intergroup differences for spinal cord injury, Cushing's syndrome, lung function, hepatitis, and rumen acidosis. These trials require independent replication. On the basis of the findings of this systematic review, there is no compelling evidence to recommend or reject acupuncture for any condition in domestic animals. Some encouraging data do exist that warrant further investigation in independent rigorous trials.

Acupuncture Analgesia↗

The efficacy of bone replacement grafts in the treatment of periodontal osseous defects. A systematic review.

BACKGROUND: Bone replacement grafts (BRG) are widely used in the treatment of periodontal osseous defects; however, the clinical benefits of this therapeutic practice require further clarification through a systematic review of randomized controlled studies. RATIONALE: The purpose of this systematic review is to access the efficacy of bone replacement grafts in proving demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone. FOCUSED QUESTION: What is the effect of bone replacement grafts compared to other interventions on clinical, radiographic, adverse, and patient-centered outcomes in patients with periodontal osseous defects? SEARCH PROTOCOL: The computerized bibliographical databases MEDLINE and EMBASE were searched from 1966 and 1974, respectively, to October 2002 for randomized controlled studies in which bone replacement grafts were compared to other surgical interventions in the treatment of periodontal osseous defects. The search strategy included screening of review articles and reference lists of retrieved articles as well as hand searches of selected journals. INCLUSION CRITERIA: All searches were limited to human studies in English language publications. EXCLUSION CRITERIA: Non-randomized observational studies (e.g., case reports, case series), publications providing summary statistics without variance estimates or data to permit computation, and studies without BRG intervention alone were excluded. DATA COLLECTION AND ANALYSIS: The therapeutic endpoints examined included changes in bone level, clinical attachment level, probing depth, gingival recession, and crestal resorption. For purposes of meta-analysis, change in bone level (bone fill) was used as the primary outcome measure, measured upon surgical re-entry or transgingival probing (sounding). MAIN RESULTS: 1. Forty-nine controlled studies met eligibility criteria and provided clinical outcome data on intrabony defects following grafting procedures. 2. Seventeen studies provided clinical outcome data on BRG materials for the treatment of furcation defects. REVIEWERS' CONCLUSIONS: 1. With respect to the treatment of intrabony defects, the results of meta-analysis supported the following conclusions: 1) bone grafts increase bone level, reduce crestal bone loss, increase clinical attachment level, and reduce probing depth compared to open flap debridement (OFD) procedures; 2) No differences in clinical outcome measures emerge between particulate bone allograft and calcium phosphate (hydroxyapatite) ceramic grafts; and 3) bone grafts in combination with barrier membranes increase clinical attachment level and reduce probing depth compared to graft alone. 2. With respect to the treatment of furcation defects, 15 controlled studies provided data on clinical outcomes. Insufficient studies of comparable design were available to submit data to meta-analysis. Nonetheless, outcome data from these studies generally indicated positive clinical benefits with the use of grafts in the treatment of Class II furcations. 3. With respect to histological outcome parameters, 2 randomized controlled studies provide evidence that demineralized freeze-dried bone allograft (DFDBA) supports the formation of a new attachment apparatus in intrabony defects, whereas OFD results in periodontal repair characterized primarily by the formation of a long junctional epithelial attachment. Multiple observational studies provide consistent histological evidence that autogenous and demineralized allogeneic bone grafts support the formation of new attachment. Limited data also suggest that xenogenic bone grafts can support the formation of a new attachment apparatus. In contrast, essentially all available data indicate that alloplastic grafts support periodontal repair rather than regeneration. 4. The results of this systematic review indicate that bone replacement grafts provide demonstrable clinical improvements in periodontal osseous defects compared to surgical debridement alone.

Alveolar Bone Loss↗

Panax ginseng: a systematic review of adverse effects and drug interactions.

Panax ginseng C. A. Meyer is a perennial herb native to Korea and China and has been used as an herbal remedy in eastern Asia for thousands of years. Modern therapeutic claims refer to vitality, immune function, cancer, cardiovascular diseases, improvement of cognitive and physical performance and sexual function. A recent systematic review of randomised controlled trials found that the efficacy of ginseng root extract could not be established beyond doubt for any of these indications. In order to obtain a balanced assessment of the therapeutic value of P. ginseng it is also necessary to consider the safety profile. In view of the extremely widespread use of P. ginseng it seems important to ask whether this herbal medicine involves health risks for the consumer. This review was conducted as a systematic attempt to document and evaluate all the available safety data on P. ginseng root extracts. Systematic searches were performed in five electronic databases and the reference lists of all papers located were checked for further relevant publications. All articles containing original data on adverse events and drug interactions with P. ginseng were included. Information was also requested from 12 manufacturers of ginseng preparations, the spontaneous reporting schemes of the WHO and national drug safety bodies. No language restrictions were imposed. Data from clinical trials suggest that the incidence of adverse events with ginseng monopreparations is similar to that with placebo. The most commonly experienced adverse events are headache, sleep and gastrointestinal disorders. The possibility of more serious adverse events is indicated in isolated case reports and data from spontaneous reporting schemes; however, causality is often difficult to determine from the evidence provided. Combination products containing ginseng as one of several constituents have been associated with serious adverse events and even fatalities. Interpretation of these cases is difficult as ingredients other than P. ginseng may have caused the problems. Possible drug interactions have been reported between P. ginseng and warfarin, phenelzine and alcohol. Collectively, these data suggest that P. ginseng monopreparations are rarely associated with adverse events or drug interactions. The ones that are documented are usually mild and transient. Combined preparations are more often associated with such events but causal attribution is usually not possible.

Clinical Trials as Topic↗

Interventions of hospital pharmacists in improving drug therapy in children: a systematic literature review.

Medicines' management or pharmaceutical care in paediatric patients is particularly demanding, mainly because the majority of available drugs have been developed for use in adults. As a result, in children, drugs are often unlicensed or used off-label, suitable formulations or appropriate strengths are lacking, and drugs have to be extemporaneously prepared, liquids and injections diluted, and tablets split. These factors increase the likelihood of medication errors and may lead to a reduction in drug effect. Age-specific changes in pharmacokinetics and pharmacodynamics further complicate drug therapy in children. All these challenges provide unique opportunities for pharmacists to improve the quality of care for paediatric patients. We conducted a systematic literature review examining whether the interventions of hospital pharmacists improve drug therapy in children. Several medical and pharmaceutical databases were searched systematically to identify articles investigating hospital pharmacists' interventions that were intended to improve drug therapy in children. Inclusion criteria were English language, primary research papers and studies in which clinical pharmacists contributed directly to patient care. Exclusion criteria were reviews, editorials, questionnaire studies, modelling studies, letters and studies only available in abstract form. This systematic search identified 18 articles documenting the role of a clinical hospital pharmacist in paediatric care. These articles were divided into the following groups based on study type: (i) studies documenting interventions made by pharmacists and their role in inpatients; (ii) articles presenting the outcomes of a satellite pharmacy; and (iii) articles examining pharmacist involvement in paediatric outpatient clinics. No randomised study comparing pharmacist interventions with standard care was found. In conclusion, although it was difficult to compare the various studies identified because of the different settings, design, duration, size, methodology and definition, all these studies highlighted the importance of hospital pharmacists to medicines' management in paediatric patients. On the basis of this review, we can conclude that pharmacist reviewing of medication charts is very important in identifying medication errors; hence, it is likely to be the most effective method of improving drug therapy in children.

Adverse Drug Reaction Reporting Systems↗

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↗

Smartphone Apps for Preventing Adolescent Health Problems Among Health Care Professionals: Systematic Search and Quality Assessment.

BACKGROUND: Health care professionals must consider multiple dimensions of prevention when consulting with adolescents. Identifying risky behaviors early in adolescence is crucial for reducing both morbidity and mortality. General practitioners are increasingly eager to incorporate digital tools for prevention into their consultations with adolescents; however, the relevance and clinical validity of these digital tools are not always established or well-known. Consequently, primary care professionals require guidance and support in selecting relevant mobile health (mHealth) tools. OBJECTIVE: The aim of this study is to identify relevant and useful digital apps to help primary care professionals detect at-risk adolescents across all recommended areas of prevention: orthopedics, mental health, substance abuse, risk behaviors, sexual health, vaccinations, social relationships, and nutrition. METHODS: A systematic review of smartphone apps, with an analysis of content quality, was carried out by 4 researchers using the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) checklist. The App Store and Google Play Store platforms were surveyed. The inclusion criteria were as follows: free of charge, date of last update, availability in French or English, relevance of the preventive approach to adolescents, and scientific validation. Four health care professionals assessed the apps: 2 selected the apps relevant to health care professionals, then 3 analyzed these apps using the French version of the Mobile App Rating Scale (MARS-F). Intraclass correlation coefficient, model (2,1) (2-way random effects, absolute agreement, single measures); standard error of measurement; and mean absolute error were also calculated. RESULTS: A total of 976 apps were identified, 49 of which had disappeared from the platforms prior to analysis. Nine apps were retained. Seven (0.72%) were included after evaluation using the MARS-F: 2 on mental health and 5 on sexual health (including 3 on contraception only). The mean MARS-F interrater score ranged from 2.5/5 to 3.8/5. The global MARS-F score demonstrated a pooled SD of 0.60 and an intraclass correlation coefficient (2,1) of 0.0003, resulting in a calculated standard error of measurement of 0.60. The average discrepancy between raters was a mean absolute error of 0.53. CONCLUSIONS: No similar studies have been identified in the literature that specifically focus on mobile apps designed to support health care professionals in delivering preventive care to adolescents. Of the 8 areas of prevention identified as relevant for adolescents, only 3 are addressed by the apps validated through our methodology (5 focus on sexual health). Consequently, current apps are insufficient to support health care professionals in their overall preventive work with adolescents. Such a review should be conducted systematically prior to the development of any new tool to prevent duplication and channel creative efforts toward truly innovative digital solutions. Furthermore, a thorough analysis of relevant, recommended websites is essential, as these resources complement the use of mobile apps designed for health care professionals.

Humans↗

Effectiveness of Wearable Digital Therapeutics in Improving Sleep Outcomes Among Individuals With Insomnia: Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Wearable devices are increasingly used for sleep monitoring and as adjunctive treatment. Existing meta-analyses mostly pool composite digital therapies and rarely isolate stand-alone wearables or distinguish between objective and subjective end points. Whether stand-alone wearable interventions improve sleep outcomes in adults with insomnia, and which factors moderate treatment heterogeneity, remains unclear. OBJECTIVE: This study aims to evaluate the effectiveness of wearable digital interventions on sleep outcomes in adults with insomnia versus control strategies and explore moderators of effectiveness, including device-wearing position, intervention duration, and control type, using meta-regression. METHODS: This systematic review and meta-analysis was conducted in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses) 2020 statement and the PRISMA-S (Preferred Reporting Items for Systematic Reviews and Meta‑Analyses Literature Search Extension) guideline. Five electronic databases and clinical trial registries were searched from inception to May 18, 2026. Eligible studies were randomized controlled trials (RCTs) evaluating wearable digital interventions in adults with insomnia compared with sham, waitlist, usual care, or active control conditions and had an intervention duration of at least 1 week. Study screening, data extraction, and risk-of-bias assessment were carried out independently by 2 reviewers. Pooled estimates were calculated using a restricted maximum likelihood random-effects model with the Hartung-Knapp-Sidik-Jonkman correction. Heterogeneity was assessed using the I² statistic, and 95% prediction intervals (PIs) were calculated for the primary analyses. The certainty of evidence was rated using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) approach. RESULTS: Sixteen RCTs (N=910) were included. Wearable digital interventions were associated with a significant reduction in objective sleep-onset latency (SOL; mean difference [MD] -4.52, 95% CI -8.38 to -0.67, PI -9.52 to 0.47 min) and a significant improvement in subjective sleep efficiency (SE; MD 2.00%, 95% CI 1.90%-2.11%, PI 1.85%-2.15%). Subjective total sleep time (TST) also showed a significant increase (MD 19.11, 95% CI 2.98-35.24, PI -16.20 to 54.43 minutes). Meta-regression showed that control type, intervention duration, and device location did not explain the heterogeneity of the insomnia severity index (ISI) (R²=0). Sensitivity analysis confirmed the robustness of pooled ISI estimates, and an Egger test indicated no small-study effects (P=.07). Certainty of evidence ranged from moderate to high. CONCLUSIONS: Wearable digital interventions provide selective benefits for objective SOL, subjective SE, and subjective TST in adults with insomnia, with no improvement in overall ISI. Despite statistically significant effects on several sleep parameters, wide PIs, substantial heterogeneity, and limited study numbers indicate preliminary, nonconclusive findings. Wearables should be viewed as affordable adjunctive tools requiring further validation, not substitutes for first-line cognitive behavioral therapy for insomnia. Large-scale, long-term RCTs with standardized protocols and patient-level external validation are required to consolidate the evidence base.

Humans↗

Systematic review of the quality of randomized controlled trials for patellofemoral pain syndrome.

STUDY DESIGN: Systematic review of the literature. OBJECTIVES: To develop a grading scale to judge the quality of randomized clinical trials (RCTs) and conduct a systematic review of the published RCTs that assess nonoperative treatments for patellofemoral pain syndrome (PFPS). BACKGROUND: Systematic reviews of the quality and usefulness of clinical trials allow for efficient synthesis and dissemination of the literature, which should facilitate clinicians' efforts to incorporate principles of evidence-based practice in the clinical decision-making process. METHODS AND MEASURES: Using a scale based on criteria in the Cochrane Collaboration Handbook, we sought to critically appraise the methodology used in RCTs related to the nonoperative management of PFPS, synthesize and interpret our results, and report our findings in a user-friendly fashion. A scale to assess the methodological quality of trials was designed and pilot tested for its content and reliability. Published RCTs identified during a literature search were then selected and rated by 6 raters. We used predefined cutoff scores to identify specific weaknesses in the clinical research process that need to be improved in future clinical trials. RESULTS: The quality scale we developed was demonstrated to be sufficiently reliable to warrant interpretation of the reviewers' findings. The percentage of trials that met a minimum level of quality for each specific criterion ranged from a low of 25% for the adequacy of the description of the randomization procedure to a high of 95% for the description and standardization of the intervention. CONCLUSIONS: Based on the results of trials exhibiting a sufficient level of quality, treatments that were effective in decreasing pain and improving function in patients with PFPS were acupuncture, quadriceps strengthening, the use of a resistive brace, and the combination of exercises with patellar taping and biofeedback. The use of soft foot orthotics in patients with excessive foot pronation appeared useful in decreasing pain. In addition, at a short-term follow-up, patients who received exercise programs were discharged earlier from physical therapy. Unfortunately, most RCTs reviewed contained qualitative flaws that bring the validity of the results into question, thus diminishing the ability to generalize the results to clinical practice. These flaws were primarily in the areas of randomization procedures, duration of follow-up, control of cointerventions, assurance of blinding, accountability and proper analysis of dropouts, number of subjects, and the relevance of outcomes. Also, given the limited number of high-quality clinical trials, recommendations about supporting or refuting specific treatment approaches may be premature and can only be made with caution.

Evidence-Based Medicine↗

A systematic review of the history and physical examination to diagnose influenza.

BACKGROUND: Although influenza is a commonly encountered condition in primary care, and diagnosis is increasingly important given the availability of new treatments, there has been no systematic review of the evidence on clinical diagnosis. METHODS: This was a systematic review of the literature with meta-analysis where appropriate. We included cohort studies and randomized trials that compared the history and physical examination with a reference laboratory test for the diagnosis of influenza A and/or B. The primary outcomes were the sensitivity, specificity, likelihood ratios, and area under the receiver-operating characteristic (ROC) curve. RESULTS: Seven studies reported the sensitivity and specificity for a total of 59 variables. We combined studies of influenza A or B alone with those of influenza A and B. Rigors [likelihood ratio (LR) +7.2], the combination of fever and presenting within 3 days of the onset of illness (LR +4.0), and sweating (LR +3.0) were best at ruling-in influenza when present. When absent, the following decreased the likelihood of influenza: any systemic symptoms (LR -0.36), coughing (LR -0.38), not being able to cope with daily activities (LR -0.39), and being confined to bed (LR -0.50). Cough, nasal congestion, and fever (subjective or objective) had the highest calculable areas under the ROC curve. CONCLUSIONS: Individual signs and symptoms are of limited value for the diagnosis of influenza. Development of clinical decision rules that systematically combine symptoms may be a more useful strategy.

Cohort Studies↗

Clinical effectiveness and cost-effectiveness of laparoscopic surgery for colorectal cancer: systematic reviews and economic evaluation.

OBJECTIVE: The aim of this study was to determine the clinical effectiveness and cost-effectiveness of laparoscopic, laparoscopically assisted (hereafter together described as laparoscopic surgery) and hand-assisted laparoscopic surgery (HALS) in comparison with open surgery for the treatment of colorectal cancer. DATA SOURCES: Electronic databases were searched from 2000 to May 2005. A review of economic evaluations was undertaken by the National Institute for Health and Clinical Excellence in 2001. This review was updated from 2000 until July 2005. REVIEW METHODS: Data from selected studies were extracted and assessed. Dichotomous outcome data from individual trials were combined using the relative risk method and continuous outcomes were combined using the Mantel-Haenszel weighted mean difference method. Summaries of the results from individual patient data (IPD) meta-analyses were also presented. An economic evaluation was also carried out using a Markov model incorporating the data from the systematic review. The results were first presented as a balance sheet for comparison of the surgical techniques. It was then used to estimate cost-effectiveness measured in terms of incremental cost per life-year gained and incremental cost per quality-adjusted life-year (QALY) for a time horizon up to 25 years. RESULTS: Forty-six reports on 20 studies [19 randomised controlled trials (RCTs) and one IPD meta-analysis] were included in the review of clinical effectiveness. The RCTs were of generally moderate quality with the number of participants varying between 16 and 1082, with 10 having less than 100 participants. The total numbers of trial participants who underwent laparoscopic or open surgery were 2429 and 2139, respectively. A systematic review of four papers suggested that laparoscopic surgery is more costly than open surgery. However, the data they provided on effectiveness was poorer than the evidence from the review of effectiveness. The estimates from the systematic review of clinical effectiveness were incorporated into a Markov model used to estimate cost-effectiveness for a time horizon of up to 25 years. In terms of incremental cost per life-year, laparoscopic surgery was found to be more costly and no more effective than open surgery. With respect to incremental cost per QALY, few data were available to differentiate between laparoscopic and open surgery. The results of the base-case analysis indicate that there is an approximately 40% chance that laparoscopic surgery is the more cost-effective intervention at a threshold willingness to pay for a QALY of pound 30,000. A second analysis assuming equal mortality and disease-free survival found that there was an approximately 50% likelihood at a similar threshold value. Broadly similar results were found in the sensitivity analyses. A threshold analysis was performed to investigate the magnitude of QALY gain associated with quicker recovery following laparoscopic surgery required to provide an incremental cost per QALY of pound 30,000. The implied number of additional QALYs required would be 0.009-0.010 compared with open surgery. CONCLUSIONS: Laparoscopic resection is associated with a quicker recovery (shorter time to return to usual activities and length of hospitalisation) and no evidence of a difference in mortality or disease-free survival up to 3 years following surgery. However, operation times are longer and a significant number of procedures initiated laparoscopically may need to be converted to open surgery. The rate of conversion may be dependent on experience in terms of both patient selection and performing the technique. Laparoscopic resection appears more costly to the health service than open resection, with an estimated extra total cost of between pound 250 and pound 300 per patient. In terms of relative cost-effectiveness, laparoscopic resection is associated with a modest additional cost, short-term benefits associated with more rapid recovery and similar long-term outcomes in terms of survival and cure rates up to 3 years. Assuming equivalence of long-term outcomes, a judgement is required as to whether the benefits associated with earlier recovery are worth this extra cost. The long-term follow-up of the RCT cohorts would be very useful further research and ideally these data should be incorporated into a wider IPD meta-analysis. Data on the long-term complications of surgery such as incisional hernias and differences in outcomes such as persisting pain would also be valuable. Once available, further data on both costs and utilities should be included in an updated model. At this point, further consideration should then be given as to whether additional data should be collected within ongoing trials. Few data were available to assess the relative merits of HALS. Ideally, there should be more data from methodologically sound RCTs. Further research is needed on whether the balance of advantages and disadvantages of laparoscopic surgery varies within subgroups based on the different stages and locations of disease. Research relating to the effect of experience on performance is also required.

Colorectal Neoplasms↗

Home treatment for mental health problems: a systematic review.

OBJECTIVE: This review investigates the effectiveness of 'home treatment' for mental health problems in terms of hospitalisation and cost-effectiveness. For the purposes of this review, 'home treatment' is defined as a service that enables the patient to be treated outside hospital as far as possible and remain in their usual place of residence. METHODS - SYSTEMATIC LITERATURE SEARCH: 'Home treatment' excluded studies focused on day, residential and foster care. The review was based on Cochrane methodology, but non-randomised studies were included if they compared two services; these were only analysed if they provided evidence of the groups' baseline clinical comparability. METHODS - REVIEW OF ECONOMIC EVALUATIONS: Economic evaluations among the studies found were reviewed against established criteria. METHODS - IDENTIFICATION OF SERVICE COMPONENTS: A three-round Delphi exercise ascertained the degree of consensus among expert psychiatrists concerning the important components of community-based services that enable them to treat patients outside hospital. The identified components were used to construct the follow-up questionnaire. METHODS - FOLLOW-UP OF AUTHORS: As a supplement to the information available in the papers, authors of all the studies were followed up for data on service components, sustainability of programmes and service utilisation. METHODS - DATA ANALYSIS: The outcome measure was mean days in hospital per patient per month over the follow-up period. (1) Comparative analysis - compared experimental to control services. It analysed all studies with available data, divided into 'inpatient-control' and 'community-control' studies, and tested for associations between service components and difference in hospital days. (2) Experimental services analysis - analysed only experimental service data and tested for associations between service components and hospital days. RESULTS - SYSTEMATIC LITERATURE SEARCH: A total of 91 studies were found, conducted over a 30-year period. The majority (87) focused on people with psychotic disorders. RESULTS - REVIEW OF ECONOMIC EVALUATIONS: Only 22 studies included economic evaluations. They provided little conclusive evidence about cost-effectiveness because of problems with the heterogeneity of services, sample size, outcome measures and quality of analysis. RESULTS - DELPHI EXERCISE: In all, 16 items were rated as 'essential', falling into six categories: home environment; skill-mix; psychiatrist involvement; service management; caseload size; and health/social care integration. There was consensus that caseloads under 25 and flexible working hours over 7 days were important, but little support for caseloads under 15 or for 24-hour services, and consensus that home visiting was essential, but not on teams being 'explicitly dedicated' to home treatment. RESULTS - RESPONSE TO FOLLOW-UP: A total of 60% of authors responded, supplying data on service components and hospital days in most cases. Other service utilisation data were far less readily available. RESULTS - SERVICE CHARACTERISATION AND CLASSIFICATION: The services were homogeneous in terms of 'home treatment function' but fairly heterogeneous in terms of other components. There was some evidence for a group of services that were multidisciplinary, had psychiatrists as integrated team members, had smaller caseloads, visited patients at home regularly and took responsibility for both health and social care. This was not a cohesive group, however. RESULTS - SUSTAINABILITY OF SERVICES: The sustainability of home treatment services was modest: less than half the services whose authors responded were still identifiable. Services were more likely to be operational if the study had found them to reduce hospitalisation significantly. RESULTS - META-ANALYSIS: Meta-analysis with heterogeneous studies is problematic. The evidence base for the effectiveness of services identifiable as 'home treatment' was not strong. Within the 'inpatient-control' study group, the mean reduction in hospitalisation was 5 days per patient per month (for 1-year studies only). No statistical significance could be measured for this result. For 'community-control' studies, the reduction in hospitalisation was negligible. Moreover, the heterogeneity of control services, the wide range of outcome measures and the limited availability of data might have confounded the analysis. Regularly visiting at home and dual responsibility for health and social care were associated with reduced hospitalisation. Evidence for other components was inconclusive. Few conclusions could be drawn from the analysis of service utilisation data. RESULTS - LOCATION: Studies were predominately from the USA and UK, more of them being from the USA. North American studies found a reduction in hospitalisation of 1 day per patient per month more than European studies. North American and European services differed on some service components, but this was unlikely to account for this finding, particularly as no difference was found in their experimental service results. CONCLUSIONS - STATE OF RESEARCH: There is a clear need for further studies, particularly in the UK. The benefit of home treatment over admission in terms of days in hospital was clear, but over other community-based alternatives was inconclusive. CONCLUSIONS - NON-RANDOMISED STUDIES: Difficulties in systematically searching for non-randomised studies may have contributed to the smaller number of such studies found (35, compared with 56 randomised controlled trials). This imbalance was compounded by a relatively poor response rate from non-randomised controlled trial authors. Including them in the analysis had little effect. CONCLUSIONS - LIMITATIONS OF THIS REVIEW: A broad area was reviewed in order to avoid the problem of analysing by service label. While reviews of narrower areas may risk implying a homogeneity of the services that is unwarranted, the current strategy has the drawback that the studies cover a range of heterogeneous services. The poor definition of control services, however, is ubiquitous in this field, however reviewed areas are defined. Inclusion of mean data for which no standard deviations were available was problematic in that it prevented measuring the significance of the main findings. The lack of availability of this data, however, is an important finding, demonstrating the difficulty in seeking certainty in this area. Only days in hospital and cost-effectiveness were analysed here. The range and lack of uniformity of measures used in this field made meta-analysis of other outcomes impossible. It should be noted, however, that the findings pertain to these aspects alone. The Delphi exercise reported here was limited in being conducted only with psychiatrists, rather than a multidisciplinary panel. Its findings were used as a framework for the follow-up and analysis. Their possible bias should be borne in mind when considering them as findings in themselves. CONCLUSIONS - IMPLICATIONS FOR CLINICIANS: The evidence base for home treatment compared with other community-based services is not strong, although it does show that home treatment reduces days spent in hospital compared with inpatient treatment. There is evidence that visiting patients at home regularly and taking responsibility for both health and social care each reduce days in hospital. CONCLUSIONS - IMPLICATIONS FOR CONSUMERS: Services that visit patients at home regularly and those that take responsibility for both health and social care are likely to reduce time spent in hospital. Psychiatrists surveyed in this review also considered support for carers to be essential. The evidence from this review, however, was that few services currently have protocols for meeting carers' needs. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH AND COMMISSIONERS: A centrally coordinated research strategy, with attention to study design, is recommended. Studies should include economic evaluations that report health and social service utilisation. Service components should be collected and reported for both experimental and control services. Studies should be designed with adequate power and longer durations of follow-up and use comparable outcome measures to facilitate meta-analysis. Research protocols should be adhered to throughout the studies. It may be advisable that independent researchers conduct studies in future. It is no longer recommended that home treatment be tested against inpatient care, or that small, localised studies replicate existing, more highly powered studies.

Adolescent↗

Clopidogrel used in combination with aspirin compared with aspirin alone in the treatment of non-ST-segment-elevation acute coronary syndromes: a systematic review and economic evaluation.

OBJECTIVES: To review systematically the clinical effectiveness and the cost-effectiveness of clopidogrel used in combination with standard therapy including aspirin, compared with standard therapy alone for the treatment of non-ST-segment elevation acute coronary syndromes (ACS). DATA SOURCES: Electronic databases. Manufacturers' submissions. REVIEW METHODS: Studies were selected using rigorous criteria. The quality of randomised controlled trials (RCTs) was assessed according to criteria based on NHS CRD Report No. 4, and the quality of systematic reviews was assessed according to the guidelines for the Database of Reviews of Effect (DARE) criteria. The quality of economic evaluations was assessed according to a specifically tailored checklist. The clinical effectiveness and cost-effectiveness of clopidogrel in combination with standard therapy compared with standard therapy alone were synthesised through a narrative review with full tabulation of the results of the included studies. In the economic evaluations, a cost-effectiveness model was constructed using the best available evidence to determine cost-effectiveness in a UK setting. RESULTS: One RCT (the CURE trial) was a randomised, double-blind, placebo-controlled trial of high quality and showed that clopidogrel in addition to aspirin was significantly more effective than placebo plus aspirin in patients with non-ST-segment elevation ACS for the composite outcome of death from cardiovascular causes, non-fatal myocardial infarction or stroke over the 9-month treatment period. However, clopidogrel was associated with a significantly higher number of episodes of both major and minor bleeding. The results from the five systematic reviews that assessed the adverse events associated with long-term aspirin use showed that aspirin was associated with a significantly higher incidence of haemorrhagic stroke, extracranial haemorrhage and gastrointestinal haemorrhage compared with placebo. Of the cost-effectiveness evidence reviewed, only the manufacturer's submission was considered relevant from the perspective of the NHS. The review of this evidence highlighted potential limitations within the submission in its use of data and in the model structure used. These limitations led to the development of a new model with the aim of providing a more reliable estimate of the cost-effectiveness from the perspective of the UK NHS. This model indicated that clopidogrel appears cost-effective compared with standard care alone in patients with non-ST-elevation ACS as long as the NHS is willing to pay GBP6078 per quality of life year (QALY). The results were most sensitive to the inclusion of additional strategies that assessed alternative treatment durations with clopidogrel. Although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. CONCLUSIONS: The results of the CURE trial indicate that clopidogrel in combination with aspirin was significantly more effective than placebo combined with aspirin in a wide range of patients with ACS. This benefit was largely related to a reduction in Q-wave myocardial infarction. There was no statistically significant benefit in relation to mortality. The trial data suggested that a substantial part of the benefit derived from clopidogrel is achieved by 3 months, with a further small benefit over the remaining 9 months of chronic treatment. The results from the base-case model suggest that treatment with clopidogrel as an adjunct to standard therapy (including aspirin) for 12 months, compared with standard therapy alone, is cost-effective in non-ST elevation ACS patients as long as the health service is willing to pay GBP6078 per additional QALY. However, although treatment with clopidogrel for 12 months remained cost-effective for the overall cohort, provisional findings indicate that the shorter treatment durations may be more cost-effective in patients at low risk. To estimate the exact length of time that clopidogrel in addition to standard therapy should be prescribed for patients with non-ST-segment ACS would require a prospective trial that randomised patients to various durations of therapy. This would accurately assess whether a 'rebound' phenomenon occurs in patients if clopidogrel were stopped after 3 months of treatment.

Acute Disease↗

A methodological review of how heterogeneity has been examined in systematic reviews of diagnostic test accuracy.

OBJECTIVES: To review how heterogeneity has been examined in systematic reviews of diagnostic test accuracy studies. DATA SOURCES: Centre for Reviews and Dissemination's Database of Abstracts of Reviews of Effects (DARE). REVIEW METHODS: Systematic reviews that evaluated a diagnostic or screening test by including studies that compared a test with a reference test were identified from DARE. Reviews for which structured abstracts had been written up to December 2002 were screened for inclusion. Data extraction was undertaken using standardised data extraction forms. RESULTS: A total of 189 systematic reviews met the inclusion criteria. The median number of studies included was 18. Meta-analyses have a higher number with a median of 22 studies compared with 11 for narrative reviews. Graphical plots to demonstrate the spread in study results were provided in 56% of meta-analyses; in 79% these were plots of sensitivity and specificity in the receiver operating characteristic (ROC) space. Statistical tests to identify heterogeneity were used in 32% of reviews: 41% of meta-analyses and 9% of reviews using narrative syntheses. The chi-squared test and Fisher's exact test to assess heterogeneity in individual aspects of test performance were the most common. In contrast, only 16% of meta-analyses used correlation coefficients to test for a threshold effect. A narrative synthesis was used in 30% of reviews. Of the meta-analyses, 52% carried out statistical pooling alone, 18% conducted only summary receiver operator characteristic (SROC) analyses and 30% used both methods of statistical synthesis. For those undertaking SROC analyses, the main differences between the models used were the weights chosen for the regression models, although in 42% of cases the use of, or choice of, weight was not provided. The proportion of reviews using statistical pooling alone has declined from 67% in 1995 to 42% in 2001, with a corresponding increase in the use of SROC methods, from 33% to 58%. However, two-thirds of those using SROC methods also carried out statistical pooling rather than presenting only SROC models. Reviews using SROC analyses also tended to present their results as some combination of sensitivity and specificity rather than using alternative, perhaps less clinically meaningful, means of data presentation such as diagnostic odds ratios. Three-quarters of meta-analyses attempted to investigate statistically possible sources of variation, using subgroup analysis or regression analysis. The impact of clinical or socio-demographic variables was investigated in 74% of these reviews and test- or threshold-related variables in 79%. At least one quality-related variable was investigated in 63% of reviews. Within this subset, the most commonly considered variables were the use of blinding, sample size, the reference test used and the avoidance of verification bias. CONCLUSIONS: The emphasis on pooling individual aspects of diagnostic test performance and the under-use of statistical tests and graphical approaches to identify heterogeneity perhaps reflect the uncertainty in the most appropriate methods to use and also greater familiarity with more traditional indices of test accuracy. This indicates the difficulty and complexity of carrying out such reviews. In these cases it is strongly suggested that meta-analyses are carried out with the involvement of a statistician familiar with the field. Further methodological work on the statistical methods available for combining diagnostic test accuracy studies is needed, as are sufficiently large, prospectively designed primary studies of diagnostic test accuracy comparing two or more tests for the same target disorder. Use of individual patient data meta-analysis in diagnostic test accuracy reviews should be explored to allow heterogeneity to be considered in more detail.

Diagnostic Tests, Routine↗

Conceptual framework and systematic review of the effects of participants' and professionals' preferences in randomised controlled trials.

OBJECTIVES: To develop a conceptual framework of preferences for interventions in the context of randomised controlled trials (RCTs), as well as to examine the extent to which preferences affect recruitment to RCTs and modify the measured outcome in RCTs through a systematic review of RCTs that incorporated participants' and professionals' preferences. Also to make recommendations on the role of participants' and professionals' preferences in the evaluation of health technologies. DATA SOURCES: Electronic databases. REVIEW METHODS: The conceptual review was carried out on published papers in the psychology and economics literature concerning concepts of relevance to patient decision-making and preferences, and their measurement. For the systematic review, studies across all medical specialities meeting strict criteria were selected. Data were then extracted, synthesised and analysed. RESULTS: Key elements for a conceptual framework were found to be that preferences are evaluations of an intervention in terms of its desirability and these preferences relate to expectancies and perceived value of the process and outcome of interventions. RCTs differed in the information provided to patients, the complexity of techniques used to provide that information and the degree to which preference elicitation may simply produce pre-existing preferences or actively construct them. Most current RCTs used written information alone. Preference can be measured in many different ways and most RCTs did not provide quantitative measures of preferences, and those that did tended to use very simple measures. The second part of the study, the systematic review included 34 RCTs. The findings gave support to the hypothesis that preferences affect trial recruitment. However, there was less evidence that external validity was seriously compromised. There was some evidence that preferences influenced outcome in a proportion of trials. However, evidence for preference effects was weaker in large trials and after accounting for baseline differences. Preference effects were also inconsistent in direction. There was no evidence that preferences influenced attrition. Therefore, the available evidence does not support the operation of a consistent and important 'preference effect'. Interventions cannot be categorised consistently on degree of participation. Examining differential preference effects based on unreliable categories ran the risk of drawing incorrect conclusions, so this was not carried out. CONCLUSIONS: Although patients and physicians often have intervention preferences, our review gives less support to the hypothesis that preferences significantly compromise the internal and external validity of trials. This review adds to the growing evidence that when preferences based on informed expectations or strong ethical objections to an RCT exist, observational methods are a valuable alternative. All RCTs in which participants and/or professionals cannot be masked to treatment arms should attempt to estimate participants' preferences. In this way, the amount of evidence available to answer questions about the effect of treatment preferences within and outwith RCTs could be increased. Furthermore, RCTs should routinely attempt to report the proportion of eligible patients who refused to take part because of their preferences for treatment. The findings also indicate a number of approaches to the design, conduct and analysis of RCTs that take account of participants' and/or professionals' preferences. This is referred to as a methodological tool kit for undertaking RCTs that incorporate some consideration of patients' or professionals' preferences. Future research into the amount and source of information available to patients about interventions in RCTs could be considered, with special emphasis on the relationship between sources inside and outside the RCT context. Qualitative research undertaken as part of ongoing RCTs might be especially useful. The processes by which this information leads to preferences in order to develop or extend the proposed expectancy--value framework could also be examined. Other areas for consideration include: how information about interventions changes participants' preferences; a comparison of the feasibility and effectiveness of different informed consent procedures; how strength of preference varies for different interventions within the same RCT and how these differences can be taken account of in the analysis; the differential effects of patients' and professionals' preferences on evidence arising from RCTs; and whether the standardised measurement of preferences within all RCTs (and analysis of the effect on outcome) would allow the rapid development of a significant evidence base concerning patient preferences, albeit in relation to a single preference design.

Attitude of Health Personnel↗