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Systematic reviews of bladder training and voiding programmes in adults: a synopsis of findings on theory and methods using metastudy techniques.

AIM: This paper reports a comparison of four Cochrane systematic reviews on bladder training and voiding programmes for the management of urinary incontinence using metastudy descriptive techniques. It presents a synopsis of findings on theory and methods for interventions. BACKGROUND: From the mid-1970s bladder training, prompted voiding, habit retraining and timed voiding have been developed and form the basis of nursing practice for the management of urinary incontinence in adults in institutional and community settings. METHODS: A synopsis of four Cochrane systematic reviews was undertaken using metastudy techniques developed for qualitative research and has provided a discursive comparison and contrast of the selection and appraisal of primary research, meta-theory and meta-method. FINDINGS: All programmes share a therapeutic focus on voiding and the degree and active participation of the client and caregiver. Bladder training focuses on the restoration of continence, while prompted voiding, habit retraining and timed voiding focus on the avoidance of incontinence. Bladder training and prompted voiding share the two characteristics of cognitive behavioural modification and active client participation. Habit retraining and timed voiding pre-empt episodes and avoid incontinence using operant conditioning rather than modifying behaviour. Variability of methods and operational terminology makes comparison between studies difficult. Use of cognitive behavioural approaches and operant conditioning need to be better understood in relation to future theory, interventions and study design. Bladder training is aimed at people who are cognitively and physically able, while the other voiding programmes are mainly used with for people with cognitive and physical impairments reliant on caregivers. CONCLUSION: The theoretical approaches underpinning bladder training and voiding programmes, their components and suitability for patients need to be re-considered when designing future studies. There is a need for long-term follow-up in future studies. Future trials should adhere to recognized standards of good practice and incorporate outcomes from existing systematic reviews to enable future meta-analysis to be undertaken. Metastudy techniques for the synthesis of qualitative research provide useful methods for the descriptive synopsis of quantitative systematic reviews.

Adult↗

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↗

Use of intravenous immunoglobulin for treatment of neurologic conditions: a systematic review.

BACKGROUND: Given the increasing use of intravenous immunoglobulin (IVIG) for various neurologic conditions and uncertainty pertaining to its benefits and harms, a systematic review was conducted of randomized controlled trials (RCTs) evaluating IVIG for all neurologic indications for which there was at least one published trial. STUDY DESIGN AND METHODS: For this systematic review, a systematic search strategy was applied to MEDLINE (1966-June 2003) and the Cochrane Register of Controlled Trials (June 2003) to identify potentially eligible RCTs comparing IVIG to placebo or an active control. All dosage regimens were considered. Abstracts were excluded, and no restriction was placed on language of publication. Two investigators independently performed data extraction with a standardized form. Measures of effect were calculated for each trial independently, and studies were pooled based on clinical and methodologic judgment as to its appropriateness. Where pooling of trials was inappropriate, a qualitative discussion of findings is provided. RESULTS AND CONCLUSIONS: Thirty-seven trials representing 14 conditions were identified. IVIG is more effective than placebo for treatment of relapsing-remitting multiple sclerosis and idiopathic chronic inflammatory demyelinating polyneuropathy. There is also potential benefit for treatment of multifocal motor neuropathy, myasthenia gravis, dermatomyositis, stiff-person syndrome, and Lambert-Eaton myasthenic syndrome. There was insufficient evidence to determine whether IVIG therapy was more effective than plasma exchange for Guillain-Barré syndrome. There was also insufficient evidence regarding paraprotein-associated polyneuropathy. No evidence of benefit was observed for secondary progressive multiple sclerosis or inclusion body myositis.

Adrenal Cortex Hormones↗

[The systematic review is the foundation of evidence based medicine. One of the most important contributions to clinical medicine of the past decade].

The traditional narrative review has been shown repeatedly to be biased, mostly towards exaggerated treatment size effects. In contrast, the systematic review follows a strict protocol regarding focused questions, explicit criteria for literature searches, inclusion and exclusion criteria, critical appraisal and a synthesis which is quantitative when appropriate. There is empirical evidence that bias is reduced and that the conclusions reached have greater validity for the construction of treatment guidelines. In this paper three sources of systematic reviews are identified: the Cochrane Library, reviews published in peer-reviewed journals, and assessments of health technology (HTA-reports). Editors are encouraged to publish systematic reviews after proper critical appraisal, and readers are advised to search for such reviews when in need of guidance on important clinical questions.

Bias↗

Hair removal policies in clean surgery: systematic review of randomized, controlled trials.

OBJECTIVE: To determine whether certain hair removal policies are better than others to prevent surgical-site infections in patients undergoing clean surgery. METHODS: Publications were retrieved by a systematic search of Medline, the Cochrane Library, and EMBASE up to February 2005. Additionally, the reference lists of all identified trials were examined. All randomized trials, quasi-randomized trials, and systematic reviews or meta-analyses of randomized or quasi-randomized trials comparing hair removal policies in clean surgery were selected. Trials involving patients undergoing cranial neurosurgery were excluded. Two reviewers independently assessed trial quality and extracted data. Disagreements were resolved by discussion with a third reviewer. Data from the original publications were used to calculate the relative risk or risk difference of surgical-site infection. Data for similar outcomes were combined in the analysis, where appropriate, with the use of a random effects model. RESULTS: Four trials were included in the review. No eligible systematic review or meta-analysis of randomized or quasi-randomized trials was found. The quality of the trials and how they were reported were generally unsatisfactory. Evidence regarding whether preoperative hair removal has any effect was inconclusive. When hair removal was considered necessary, evidence about the best time for removal was inconclusive. There was some evidence that hair removal by clipper is superior to removal by razor. CONCLUSIONS: Because of insufficient evidence as a basis for recommendations, the practical consequences for ward management were essential when the Dutch Working Party on Infection Prevention formulated its recommendations for hair removal policies. Large randomized, controlled trials are needed to determine the optimal policy for preoperative hair removal.

Hair Removal↗

Radiographic measurement parameters in thoracolumbar fractures: a systematic review and consensus statement of the spine trauma study group.

STUDY DESIGN: Systematic review. OBJECTIVES: To review the various radiographic parameters currently used to assess traumatic thoracolumbar injuries, emphasizing the validity and technique behind each one, to formulate evidence-based guidelines for a standardized radiographic method of assessment of these fractures. SUMMARY OF BACKGROUND DATA: The treatment of thoracolumbar fractures is guided by various radiographic measurement parameters. Unfortunately, for each group of parameters, there has usually been more than 1 proposed measurement technique, thus creating confusion when gathering data and reporting outcomes. Ultimately, this effect results in clinical decisions being based on nonstandardized, nonvalidated outcome measures. METHODS: Computerized bibliographic databases were searched up to January 2004 using key words and Medical Subject Headings on thoracolumbar spine trauma, radiographic parameters, and methodologic terms. Using strict inclusion criteria, 2 independent reviewers conducted study selection, data abstraction, and methodologic quality assessment. RESULTS: There were 18 original articles that ultimately constituted the basis for the review. Of radiographic measurement parameters, 3 major groups were identified, depicting the properties of the injured spinal column: sagittal alignment, vertebral body compression, and spinal canal dimensions, with 14 radiographic parameters reported to assess these properties. CONCLUSIONS: Based on a systematic review of the literature and expert opinion from an experienced group of spine trauma surgeons, it is recommended that the following radiographic parameters should be used routinely to assess thoracolumbar fractures: the Cobb angle, to assess sagittal alignment; vertebral body translation percentage, to express traumatic anterolisthesis; anterior vertebral body compression percentage, to assess vertebral body compression, the sagittal-to-transverse canal diameter ratio, and canal total cross-sectional area (measured or calculated); and the percent canal occlusion, to assess canal dimensions.

Consensus↗

Identifying studies for systematic reviews. An example from medical imaging.

OBJECTIVES: To determine if published figures on the proportion of articles included in systematic reviews and identified in electronic databases are applicable to an example from medical imaging. METHODS: A systematic review was performed. Additionally, sensitivity and precision of a MEDLINE search were compared with values from three published searches, each customized for a specific field. RESULTS: All articles included in the systematic review were in electronic databases. The MEDLINE search had low precision compared with searches in other fields. CONCLUSIONS: In a specific area of medical imaging, electronic databases, including MEDLINE, are reliable sources of articles.

Bibliometrics↗

Patient Ethnicity and Staff Use of Restraints and Restrictive Practice in Inpatient Psychiatric Services: A Systematic Review.

Restrictive practices such as restraints, seclusion, and forced medication are only intended to be used when the threat is at a level whereby an individual is likely to inflict harm on themselves or another individual. Demographic variations, including ethnicity, may be associated with the use of these practices. However, there is no systematic review on patient ethnicity specifically. The review therefore aimed to establish whether a patient's ethnic identity was associated with staff use of restrictive practices in inpatient psychiatric services. The systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Four databases were searched (PsycINFO, Medline, Embase, and CINAHL). Methodological quality was assessed using the Critical Appraisal Skills Program Checklists. Fifteen studies met the inclusion criteria. A variety of ethnicities were identified within the studies. These were driven by the location of the study. Seclusion (14 studies), forced medication (4), and physical restraint (4) were explored. There were mixed findings, with ethnicity shown to predict restrictive practices in studies having larger participant numbers, longer follow-up periods and less methodological bias. It remains unclear whether ethnicity is a genuinely independent predictor of restraint and coercive practices or interacts with other risk factors. Staff working in inpatient settings should be aware of how unconscious biases might affect clinical practice. Recruiting a diverse workforce from minority ethnic groups into inpatient psychiatric services would be a positive step. However, support for these staff members is important, and all staff should be equipped to respond to ethnic diversity. Future research should explore beyond patient-level factors.

Humans↗

Postoperative chemoradiotherapy for advanced squamous cell carcinoma of the head and neck: a systematic review with meta-analysis.

BACKGROUND: This systematic review evaluates the use of postoperative chemoradiotherapy for patients with advanced (stage III or IV) squamous cell carcinoma of the head and neck at a high risk of recurrence. METHODS: The literature was systematically searched for eligible randomized controlled trials (RCTs). RESULTS: Of 4 RCTs identified, 3 reported improvements in locoregional control, 3 reported improved disease-free or progression-free survival, and 3 reported improved overall survival with chemoradiotherapy compared with radiotherapy alone. Pooling trials confirmed the benefit for chemoradiotherapy in locoregional recurrence (relative risk [RR] = 0.59; 95% confidence interval [CI] = 0.47-0.75; p < .00001) and overall survival (RR = 0.80; 95% CI = 0.71-0.90; p = .0002). More frequent and severe acute mucosal toxicity was reported with combined treatment. CONCLUSIONS: Postoperative adjuvant chemoradiotherapy is superior to radiotherapy alone. Because chemoradiotherapy is associated with significantly increased toxicity, further investigations to identify patients most likely to benefit or toxicity reduction strategies are warranted.

Carcinoma, Squamous Cell↗

A quantitative, systematic review of randomized controlled trials of ephedrine versus phenylephrine for the management of hypotension during spinal anesthesia for cesarean delivery.

UNLABELLED: This quantitative systematic review compared the efficacy and safety of ephedrine with phenylephrine for the prevention and treatment of hypotension during spinal anesthesia for cesarean delivery. Seven randomized controlled trials (n = 292) were identified after a systematic search of electronic databases (MEDLINE, EMBASE, The Cochrane Controlled Trials Registry), published articles, and contact with authors. Outcomes assessed were maternal hypotension, hypertension and bradycardia, and neonatal umbilical cord blood pH values and Apgar scores. For the management (prevention and treatment) of maternal hypotension, there was no difference between phenylephrine and ephedrine (relative risk [RR] of 1.00; 95% confidence interval [CI], 0.96-1.06). Maternal bradycardia was more likely to occur with phenylephrine than with ephedrine (RR of 4.79; 95% CI, 1.47-15.60). Women given phenylephrine had neonates with higher umbilical arterial pH values than those given ephedrine (weighted mean difference of 0.03; 95% CI, 0.02-0.04). There was no difference between the two vasopressors in the incidence of true fetal acidosis (umbilical arterial pH value of <7.2; RR of 0.78; 95% CI, 0.16-3.92) or Apgar score of <7 at 1 and 5 min. This systematic review does not support the traditional idea that ephedrine is the preferred choice for the management of maternal hypotension during spinal anesthesia for elective cesarean delivery in healthy, nonlaboring women. IMPLICATIONS: Phenylephrine and ephedrine to manage hypotension during spinal anesthesia for elective cesarean delivery were compared in this systematic review. Women given ephedrine had neonates with lower umbilical cord blood pH values compared with those given phenylephrine. However, no differences in the incidence of fetal acidosis (pH value of <7.2) or neonatal Apgar scores were found.

Anesthesia, Obstetrical↗

Screening for lung cancer: a systematic review and meta-analysis of controlled trials.

BACKGROUND: Lung cancer is a substantial public health problem in western countries. Previous studies have examined different screening strategies for lung cancer but there have been no published systematic reviews. METHODS: A systematic review of controlled trials was conducted to determine whether screening for lung cancer using regular sputum examinations or chest radiography or computed tomography (CT) reduces lung cancer mortality. The primary outcome was lung cancer mortality; secondary outcomes were lung cancer survival and all cause mortality. RESULTS: One non-randomised controlled trial and six randomised controlled trials with a total of 245 610 subjects were included in the review. In all studies the control group received some type of screening. More frequent screening with chest radiography was associated with an 11% relative increase in mortality from lung cancer compared with less frequent screening (RR 1.11, 95% CI 1.00 to 1.23). A non-statistically significant trend to reduced mortality from lung cancer was observed when screening with chest radiography and sputum cytological examination was compared with chest radiography alone (RR 0.88, 95% CI 0.74 to 1.03). Several of the included studies had potential methodological weaknesses. Controlled studies of spiral CT scanning have not been reported. CONCLUSIONS: The current evidence does not support screening for lung cancer with chest radiography or sputum cytological examination. Frequent chest radiography might be harmful. Further methodologically rigorous trials are required before any new screening methods are introduced into clinical practice.

Controlled Clinical Trials as Topic↗

Assessing the quality of reports of systematic reviews in pediatric complementary and alternative medicine.

OBJECTIVE: To examine the quality of reports of complementary and alternative medicine (CAM) systematic reviews in the pediatric population. We also examined whether there were differences in the quality of reports of a subset of CAM reviews compared to reviews using conventional interventions. METHODS: We assessed the quality of reports of 47 CAM systematic reviews and 19 reviews evaluating a conventional intervention. The quality of each report was assessed using a validated 10-point scale. RESULTS: Authors were particularly good at reporting: eligibility criteria for including primary studies, combining the primary studies for quantitative analysis appropriately, and basing their conclusions on the data included in the review. Reviewers were weak in reporting: how they avoided bias in the selection of primary studies, and how they evaluated the validity of the primary studies. Overall the reports achieved 43% (median = 3) of their maximum possible total score. The overall quality of reporting was similar for CAM reviews and conventional therapy ones. CONCLUSIONS: Evidence based health care continues to make important contributions to the well being of children. To ensure the pediatric community can maximize the potential use of these interventions, it is important to ensure that systematic reviews are conducted and reported at the highest possible quality. Such reviews will be of benefit to a broad spectrum of interested stakeholders.

Age Distribution↗

Evidence that metastasis is less common in cirrhotic than normal liver: a systematic review of post-mortem case-control studies.

BACKGROUND: It has been hypothesized that the cirrhotic liver is afforded protection against metastasis. The evidence has been examined and the plausibility of such a phenomenon is reviewed. METHODS: A systematic literature review was conducted with analysis of combined data from post-mortem case-control studies. RESULTS: Overall, the crude rate of metastasis to normal liver was 37.3 per cent, while the rate to cirrhotic liver was 23.7 per cent. The Mantel-Haenszel (MH) fixed-effects estimate of the odds ratio was 0. 47 (95 per cent confidence interval (c.i.) 0.41-0.53; chi2 = 136, 11 d.f., P < 0.001). The DerSimonian-Laird (DL) random-effects estimation of the odds ratio was 0.42 (95 per cent c.i. 0.31-0.58; chi2 = 28, 1 d.f., P < 0.001). For tumours arising within the distribution of the portal vein, the crude rate of metastasis to normal liver was 47.6 per cent, whereas the rate to cirrhotic liver was 29.8 per cent. The MH estimate of the odds ratio was 0.45 (95 per cent c.i. 0.37-0.54; chi2 = 68.2, 5 d.f., P < 0.001). The DL pooled odds ratio was 0.44 (95 per cent c.i. 0.28-0.70; chi2 = 12.3, 1 d.f., P < 0.001). The MH and DL pooled estimates of the odds ratio were similar for groups of patients from the East (Japan) and the West (Europe and the USA). CONCLUSION: The post-mortem evidence reviewed suggests that the likelihood of metastasis to the cirrhotic liver is lower than that to normal liver. The degree of protection for tumours arising from within the distribution of the portal vein is neither greater nor less than it is overall. Eastern and Western populations appear to have a similar degree of risk reduction. The differences noted were significant on testing in the meta-analysis, but confounding bias accounting for these differences has not been excluded.

Autopsy↗

Methods for systematic reviews of economic evaluations for the Guide to Community Preventive Services. Task Force on Community Preventive Services.

OBJECTIVES: This paper describes the methods used in the Guide to Community Preventive Services: Systematic Reviews and Evidence-Based Recommendations (the Guide) for conducting systematic reviews of economic evaluations across community health-promotion and disease-prevention interventions. The lack of standardized methods to improve the comparability of results from economic evaluations has hampered the use of data on costs and financial benefits in evidence-based reviews of effectiveness. The methods and instruments developed for the Guide provide an explicit and systematic approach for abstracting economic evaluation data and increase the usefulness of economic information for policy making in health care and public health. METHODS: The following steps were taken for systematic reviews of economic evaluations: (1) systematic searches were conducted; (2) studies using economic analytic methods, such as cost analysis or cost-effectiveness, cost-benefit or cost-utility analysis, were selected according to explicit inclusion criteria; (3) economic data were abstracted and adjusted using a standardized abstraction form; and (4) adjusted summary measures were listed in summary tables. RESULTS: These methods were used in a review of 10 interventions designed to improve vaccination coverage in children, adolescents and adults. Ten average costs and 14 cost-effectiveness ratios were abstracted or calculated from data reported in 24 studies and expressed in 1997 USD. The types of costs included in the analysis and intervention definitions varied extensively. Gaps in data were found for many interventions.

Abstracting and Indexing↗

Surgical treatment of traumatic fractures of the thoracic and lumbar spine: a systematic review of the literature on techniques, complications, and outcome.

STUDY DESIGN: A systematic review of the literature, pertaining surgical treatment of traumatic thoracic and lumbar spine fractures, was performed. OBJECTIVES: To provide information on surgical techniques for traumatic spine fracture management, their respective performance and complication rates, based on previously published information. SUMMARY OF BACKGROUND DATA: The treatment of traumatic fractures of the thoracic and lumbar spine remains controversial. There is insufficient evidence in the literature to choose between the various surgical options. In absence of conclusive studies, a systematic review can be an alternative to obtain more convincing information. METHODS: Full-text papers from 1970 until 2001 were included if strict inclusion criteria were met. Five surgical subgroups were recognized: posterior short-segment (PS), posterior long-segment (PL), reports on both posterior short- and long-segment (PSL), anterior (A), and anterior combined with posterior (AP) techniques. Clearly defined and generally accepted parameters were scored and subsequently analyzed. The preoperative injury severity of the surgical groups was compared. The neurologic, radiologic, and functional outcome and complications of all groups were assessed. RESULTS: A total of 132 papers, the majority being retrospective case-series, were included representing 5,748 patients. The preoperative injury severity revealed an inequality between the subgroups. Partial neurologic deficits had the potential to resolve irrespective of treatment choice. None of the five techniques used was able to maintain the corrected kyphosis angle. The functional outcome after surgery seems to be better than generally believed. Complications are relatively rare. CONCLUSIONS: In general, surgical treatment of traumatic spine fractures is safe and effective. Surgical techniques can only be compared using randomized controlled trials.

Adult↗

Artificial intelligence for anticancer drug discovery from natural products of macroalgae and sponges: A systematic review.

Marine natural products (MNPs) from macroalgae and marine sponges have inspired clinically important anticancer agents, including the cytarabine pharmacophore and the eribulin scaffold, while cyanobacterial dolastatin chemistry supplies the auristatin payloads of several marine-inspired antibody-drug conjugates (ADCs) such as brentuximab vedotin. Artificial intelligence (AI) methods, encompassing both classical machine learning (ML) with hand-engineered features and modern deep learning (DL) with many-layered neural networks, are increasingly supporting key decisions in natural-product anticancer drug discovery, including bioactivity prediction, target identification, absorption, distribution, metabolism, excretion and toxicity (ADMET) filtering, generative analogue design, and the selection of preclinical candidates. DL architectures relevant to this field include graph neural networks, transformer-based molecular generators, diffusion models for protein-ligand docking, and convolutional networks for mass spectrometry, while classical ML contributes interpretable fingerprint-based bioactivity models and molecular networking for dereplication. This review follows a systematic literature review methodology to organize the landscape of AI methods now applied to MNP anticancer discovery, distinguishing ML and DL approaches where relevant, situating them within the chemical context of macroalgal and sponge-derived oncology leads, and critically examining published case studies, including validation level (computational, in vitro, in vivo, clinical). The principal bottleneck for medical translation has shifted partly from algorithmic capability toward data infrastructure and experimental validation. Sparse, heterogeneous, and taxonomically biased bioactivity records limit what current models can learn and reduce the reliability of AI-prioritized candidates entering the preclinical pipeline. A roadmap is proposed that prioritizes open MNP-specific benchmarks, symbiont-aware modeling, and active learning loops with synthesizability and ADMET constraints. These AI workflows may accelerate the prioritization of marine-derived anticancer leads and support earlier, more evidence-based translational decisions in oncology drug development.

Biological Products↗

Assessing "best evidence": issues in grading the quality of studies for systematic reviews.

BACKGROUND: Evidence-based medicine, clinical practice guidelines, quality and value of health services, and science-based decision making are becoming mainstays of the health care sector. As part of the evidence-based movement, systematic reviews of the literature on clinical questions are becoming increasingly common. Part of the structured approach to evaluating the literature involves assessing the quality of individual studies included in systematic reviews. REVIEW QUESTIONS: To clarify issues in this area, in 1998 the Agency for Health Care Policy and Research commissioned a small project to determine how its 12 Evidence-based Practice Centers were carrying out this part of their systematic reviews (called evidence reports). The number of potential checklists, scales, and similar tools for grading the methodology or the clinical relevance of individual reports is large; the reliability, the validity, the feasibility, and the utility of these tools are either unmeasured or quite variable. CONCLUSIONS: Numerous methodologic questions await definitive research and answers, but in the meantime teams developing authoritative systematic reviews can take certain steps to ensure that their approaches to grading the quality of articles meet applicable scientific standards. Clinicians, program administrators, and health policymakers can then be confident in the overall strength of the evidence and study conclusions.

Bias↗

Increasing response rates to postal questionnaires: systematic review.

OBJECTIVE: To identify methods to increase response to postal questionnaires. DESIGN: Systematic review of randomised controlled trials of any method to influence response to postal questionnaires. STUDIES REVIEWED: 292 randomised controlled trials including 258 315 participants INTERVENTION REVIEWED: 75 strategies for influencing response to postal questionnaires. MAIN OUTCOME MEASURE: The proportion of completed or partially completed questionnaires returned. RESULTS: The odds of response were more than doubled when a monetary incentive was used (odds ratio 2.02; 95% confidence interval 1.79 to 2.27) and almost doubled when incentives were not conditional on response (1.71; 1.29 to 2.26). Response was more likely when short questionnaires were used (1.86; 1.55 to 2.24). Personalised questionnaires and letters increased response (1.16; 1.06 to 1.28), as did the use of coloured ink (1.39; 1.16 to 1.67). The odds of response were more than doubled when the questionnaires were sent by recorded delivery (2.21; 1.51 to 3.25) and increased when stamped return envelopes were used (1.26; 1.13 to 1.41) and questionnaires were sent by first class post (1.12; 1.02 to 1.23). Contacting participants before sending questionnaires increased response (1.54; 1.24 to 1.92), as did follow up contact (1.44; 1.22 to 1.70) and providing non-respondents with a second copy of the questionnaire (1.41; 1.02 to 1.94). Questionnaires designed to be of more interest to participants were more likely to be returned (2.44; 1.99 to 3.01), but questionnaires containing questions of a sensitive nature were less likely to be returned (0.92; 0.87 to 0.98). Questionnaires originating from universities were more likely to be returned than were questionnaires from other sources, such as commercial organisations (1.31; 1.11 to 1.54). CONCLUSIONS: Health researchers using postal questionnaires can improve the quality of their research by using the strategies shown to be effective in this systematic review.

Data Collection↗