Moderate Evidence Research Articles

ESR Essentials: imaging of middle ear cholesteatoma-practice recommendations by the European Society of Head and Neck Radiology.

Although non-malignant,middle ear cholesteatoma can result in significant complications due to local bone erosion and infection. The treatment of cholesteatoma is surgical, but residual disease is common and may be clinically occult, particularly when the canal wall is preserved or reconstructive techniques are employed. Imaging plays a pivotal role in the management of patients with middle ear cholesteatoma-aiding clinical diagnosis, identifying complications, planning surgery, and detecting residual disease at follow-up. Computed tomography is the primary imaging tool in the preoperative setting since it canprovide botha surgical roadmap and detect erosive complications of cholesteatoma. The ability of magnetic resonance imaging with non-echoplanar diffusion-weighted sequences to accurately detect residual disease has led to a shift in the diagnostic paradigm for post-surgical follow-up of cholesteatoma, such that routine "second-look" surgery is no longer required. The following practice recommendations are aimed athelping the radiologist choose appropriate imaging approaches and understand the key diagnostic considerations for the evaluation of pre- and post-surgical middle ear cholesteatoma. KEY POINTS: In the preoperative setting, CT is the first-line imaging modality and MRI is reserved for rare clinical scenarios (low evidence). Non-echoplanar imaging (EPI) DWI is the optimal MRI sequence for the detection of residual cholesteatoma (moderate evidence). Non-EPI DWI plays an important role in the postoperative surveillance of cholesteatoma (moderate evidence).

Substantiating the Use of Tendotonometry for the Assessment of Achilles and Patellar Tendon Stiffness: A Systematic Review.

To systematically describe the next relevant aspects of tendotonometry in (1) its validity and reliability, (2) differences between populations, (3) the effect of interventions, and (4) differences between healthy and symptomatic Achilles tendon (AT) and patellar tendon (PT). Three online databases (PubMed, Embase, and EBSCOhost) were systematically searched on the 10th of October 2023. All scientific literature concerning the use of tendotonometry in assessing tendon stiffness was collected. Articles were eligible if tendotonometry with a myotonometer digital palpation device was used to assess PT or AT stiffness in adults. Thirty-four studies were included, which were categorized into studies regarding the (1a) reliability and (1b) validity of tendotonometry, (2) differences in stiffness between populations, (3) changes in stiffness due to interventions, (4) stiffness of healthy compared with injured tendons, and (5) other observational studies. The inter-rater and intrarater reliability of tendotonometry appeared to be good in assessing AT and PT stiffness, with only moderate evidence for the AT and inconclusive evidence for the PT. There is high certainty evidence that tendotonometry can detect differences in AT and PT stiffness after training interventions. Inconsistent results were found for the adequacy of tendotonometry to detect differences in AT and PT stiffness between populations. This review shows a potential role for tendotonometry in measuring tendon stiffness. However, more research is needed for validating the use of tendotonometry in AT and PT and its exact clinical interpretation.

Screening instruments for early identification of unmet palliative care needs: a systematic review and meta-analysis

BackgroundThe early detection of individuals who require palliative care is essential for the timely initiation of palliative care services. This systematic review and meta-analysis aimed to (1) Identify the screening...

How exome sequencing improves the diagnostics and management of men with non-syndromic infertility.

Male infertility affects approximately 17% of all men and represents a complex disorder in which not only semen parameters such as sperm motility, morphology, and number of sperm are highly variable, but also testicular phenotypes range from normal spermatogenesis to complete absence of germ cells. Genetic factors significantly contribute to the disease but chromosomal aberrations, mostly Klinefelter syndrome, and microdeletions of the Y-chromosome have remained the only diagnostically and clinically considered genetic causes. Monogenic causes remain understudied and, thus, often unidentified, leaving the majority of the male factor couple infertility pathomechanistically unexplained. This has been changing mostly because of the introduction of exome sequencing that allows the analysis of multiple genes in large patient cohorts. As a result, pathogenic variants in single genes have been associated with non-syndromic forms of all aetiologic sub-categories in the last decade. This review highlights the contribution of exome sequencing to the identification of novel disease genes for isolated (non-syndromic) male infertility by presenting the results of a comprehensive literature search. Both, reduced sperm count in azoospermic and oligozoospermic patients, and impaired sperm motility and/or morphology, in asthenozoospermic and/or teratozoospermic patients are highly heterogeneous diseases with well over 100 different candidate genes described for each entity. Applying the standardized evaluation criteria of the ClinGen gene curation working group, 70 genes with at least moderate evidence to contribute to the disease are highlighted. The implementation of these valid disease genes in clinical exome sequencing is important to increase the diagnostic yield in male infertility and, thus, improve clinical decision-making and appropriate genetic counseling. Future advances in androgenetics will continue to depend on large-scale exome and genome sequencing studies of comprehensive international patient cohorts, which are the most promising approaches to identify additional disease genes and provide reliable data on the gene-disease relationship.

Physicians' knowledge, attitudes, and practices regarding fibromyalgia: A systematic review and meta-analysis of cross-sectional studies.

The diagnosis, etiology, and optimal management of fibromyalgia remains contentious. This uncertainty may result in variability in clinical management. We conducted a systematic review and meta-analysis of cross-sectional studies examining physicians' knowledge, attitudes, and practices regarding fibromyalgia. We searched MEDLINE, Embase, and PubMed from inception to February 2023 for cross-sectional surveys evaluating physicians' attitudes toward, and management of, fibromyalgia. Pairs of independent reviewers conducted article screening, data extraction, and risk of bias assessment in duplicate. We used random-effects meta-analysis to pool proportions for items reported by more than one study and the Grading of Recommendations Assessment, Development, and Evaluation approach to summarize the certainty of evidence. Of 864 citations, 21 studies (8904 participants) were eligible for review. Most physicians endorsed fibromyalgia as a distinct clinical entity (84%; 95% confidence interval [CI], 74-92), and half (51%; 95% CI, 40-62) considered fibromyalgia a psychosocial condition. Knowledge of formal diagnostic criteria for fibromyalgia was more likely among rheumatologists (69%, 95% CI, 45-89) versus general practitioners (38%, 95% CI, 24-54) (P = .04). Symptom relief was endorsed as the primary management goal by most physicians (73%, 95% CI, 52-90). Exercise, physiotherapy, antidepressants, nonsteroidal anti-inflammatory drugs, and non-opioid analgesics were most endorsed for management of fibromyalgia, but with wide variability between surveys. Opioids and most complementary and alternative interventions (e.g., homeopathy, chiropractic, and massage) received limited endorsement. There is moderate certainty evidence to suggest that physicians are divided regarding whether fibromyalgia is a biomedical or psychosocial disorder. Physicians typically prioritize symptom relief as the primary goal of management, and often endorse management with exercise, non-opioid analgesics, nonsteroidal anti-inflammatory drugs, antidepressants, and physiotherapy (moderate to high certainty evidence); however, important practice variation exists.

Examining the lateralization of electrophysiological correlates of auditory awareness.

The neurological basis for perceptual awareness remains unclear, and theories disagree as to whether sensory cortices per se generate awareness. Critically, neural activity in the sensory cortices is only a neural correlate of consciousness (NCC) if it closely matches the contents of perceptual awareness. Research in vision and touch suggest that contralateral activity in sensory cortices is an NCC. Similarly, research in hearing with two sound sources (left and right) presented over headphones also suggests that a candidate NCC called the auditory awareness negativity (AAN) matches perceived location of sound. The current study used 13 different sound sources presented over loudspeakers for natural localization cues and measured event-related potentials to a threshold stimulus in a sound localization task. Preregistered Bayesian mixed models provided moderate evidence against an overall AAN and very strong evidence against its lateralization. Because of issues regarding data quantity and quality, exploratory analyses with aggregated data from multiple loudspeakers were conducted. Results provided moderate evidence for an overall AAN and strong evidence against its lateralization. Nonetheless, the interpretations of these results remain inconclusive. Therefore, future research should reduce the number of conditions and/or test over several sessions to procure a sufficient amount of data. Taken at face value, the results may suggest issues with AAN as an NCC of auditory awareness, as it does not laterally map onto experiences in a free-field auditory environment, in contrast to the NCCs of vision and touch.

Paracetamol Combination Therapy for Back Pain and Osteoarthritis: A Systematic Review and Meta-Analyses.

Although paracetamol (acetaminophen) combined with other analgesics can reduce pain intensity in some pain conditions, its effectiveness in managing low back pain and osteoarthritis is unclear. This systematic review investigated whether paracetamol combination therapy is more effective and safer than monotherapy or placebo in low back pain and osteoarthritis. Online database searches were conducted for randomised trials that evaluated paracetamol combined with another analgesic compared to a placebo or the non-paracetamol ingredient in the combination (monotherapy) in low back pain and osteoarthritis. The primary outcome was a change in pain. Secondary outcomes were (serious) adverse events, changes in disability and quality of life. Follow-up was immediate (≤ 2 weeks), short (> 2 weeks but ≤ 3 months), intermediate (> 3 months but < 12 months) or long term (≥ 12 months). A random-effects meta-analysis was conducted. Risk of bias was assessed using the original Cochrane tool, and quality of evidence using Grading of Recommendations Assessment, Development and Evaluation (GRADE). Twenty-two studies were included. Pain was reduced with oral paracetamol plus a non-steroidal anti-inflammatory drug (NSAID) at immediate term in low back pain (paracetamol plus ibuprofen vs ibuprofen [mean difference (MD) - 6.2, 95% confidence interval (CI) -10.4 to -2.0, moderate evidence]) and in osteoarthritis (paracetamol plus aceclofenac vs aceclofenac [MD - 4.7, 95% CI - 8.3 to - 1.2, moderate certainty evidence] and paracetamol plus etodolac vs etodolac [MD - 15.1, 95% CI - 18.5 to - 11.8; moderate certainty evidence]). Paracetamol plus oral tramadol reduced pain compared with placebo at intermediate term for low back pain (MD - 11.7, 95% CI - 19.2 to - 4.3; very low certainty evidence) and osteoarthritis (MD - 6.8, 95% CI - 12.7 to -0.9; moderate certainty evidence). Disability scores improved in half the comparisons. Quality of life was infrequently measured. All paracetamol plus NSAID combinations did not increase the risk of adverse events compared to NSAID monotherapy. Low-to-moderate quality evidence supports the oral use of some paracetamol plus NSAID combinations for short-term pain relief with no increased risk of harm for low back pain and osteoarthritis compared to its non-paracetamol monotherapy comparator.

Supermarket Opening in an Urban, Low-Income Community Was Not Found to Be Associated With Improvements in Dietary Outcomes for Most Residents in the First Year

BackgroundLimited access to healthy foods in low-income, racial and ethnic minority communities has been proposed as a critical factor contributing to health disparities. One policy option for improving access is to introduce supermarkets in low-income communities, but evidence increasingly points to null effects. ObjectiveThe aim of this study was to examine whether the introduction of a new supermarket in a public housing community, and proximity to it, were associated with improvements in residents’ dietary outcomes. It also explored whether these associations may be moderated by access and cost barriers to eating healthy at baseline. DesignA cohort of public housing residents were recruited from Jordan Downs, where the new supermarket was introduced, and from 2 comparison sites. Longitudinal data on outcomes and exposures were collected at baseline (2018-2019) and follow-up (2020-2021). Quasi-experimental variation in residents’ distance to the new supermarket was used to examine whether proximity to the supermarket was associated with dietary improvements. Participants/settingParticipants included 557 adult residents from 3 public housing sites in Watts, Los Angeles, CA. InterventionThe intervention is the opening of a new supermarket in the Jordan Downs community. The primary exposure measure is an indicator for whether residents lived in Jordan Downs vs in the comparison sites. The secondary exposure measure is residents’ driving distance to the new supermarket. Main outcome measuresSelf-reports of daily consumption of whole grains, dairy, fruits and vegetables, added sugar, red meat, processed meat, and overall healthiness of diet were obtained from surveys administered at baseline and follow-up. Statistical analyses performedDescriptive analyses examined households’ grocery shopping patterns after the new supermarket’s introduction. Analysis of covariance linear regressions models estimated the association between residents’ dietary outcomes at follow-up and the exposure measures, conditional on dietary outcomes at baseline and other covariates. ResultsProximity to the new supermarket was associated with a significantly higher probability of shopping there, particularly for households that reported an access or cost barrier at baseline. Overall, there were no statistically significant or practically meaningful differences observed in dietary outcomes between Jordan Downs residents and those in comparison sites, or between residents who lived at varying distances from the supermarket. Exploratory moderation analyses suggested some meaningful dietary benefits for those who had a frequent access barrier at baseline, but not for those without such a barrier, but there was mostly no evidence of moderation by price barrier at baseline. ConclusionsSupermarket opening in an urban, low-income, and racial and ethnic minority community was not found to be associated with improvements in dietary outcomes for most residents in the first year after its opening. Improving dietary outcomes in such communities may require a broader and nuanced approach that addresses varied barriers faced by residents.

Exploration of resting-state brain functional connectivity as preclinical markers for arousal prediction in prolonged disorders of consciousness: A pilot study based on functional near-infrared spectroscopy.

There is no diagnostic assessment procedure with moderate or strong evidence of use, and evidence for current means of treating prolonged disorders of consciousness (pDOC) is sparse. This may be related to the fact that the mechanisms of pDOC have not been studied deeply enough and are not clear enough. Therefore, the aim of this study was to explore the mechanism of pDOC using functional near-infrared spectroscopy (fNIRS) to provide a basis for the treatment of pDOC, as well as to explore preclinical markers for determining the arousal of pDOC patients. Five minutes resting-state data were collected from 10 pDOC patients and 13healthy adults using fNIRS. Based on the concentrations of oxyhemoglobin (HbO) and deoxyhemoglobin (HbR) in the time series, the resting-state cortical brain functional connectivity strengths of the two groups were calculated, and the functional connectivity strengths of homologous and heterologous brain networks were compared at the sensorimotor network (SEN), dorsal attention network (DAN), ventral attention network (VAN), default mode network (DMN), frontoparietal network (FPN), and visual network (VIS) levels. Univariate binary logistic regression analyses were performed on brain networks with statistically significant differences to identify brain networks associated with arousal in pDOC patients. The receiver operating characteristic (ROC) curves were further analyzed to determine the cut-off value of the relevant brain networks to provide clinical biomarkers for the prediction of arousal in pDOC patients. The results showed that the functional connectivity strengths of oxyhemoglobin (HbO)-based SEN∼SEN, VIS∼VIS, DAN∼DAN, DMN∼DMN, SEN∼VIS, SEN∼FPN, SEN∼DAN, SEN∼DMN, VIS∼FPN, VIS∼DAN, VIS∼DMN, HbR-based SEN∼SEN, and SEN∼DAN were significantly reduced in the pDOC group and were factors that could reflect the participants' state of consciousness. The cut-off value of resting-state functional connectivity strength calculated by ROC curve analysis can be used as a potential preclinical marker for predicting the arousal state of subjects. Resting-state functional connectivity strength of cortical networks is significantly reduced in pDOC patients. The cut-off values of resting-state functional connectivity strength are potential preclinical markers for predicting arousal in pDOC patients.

Overall survival with non-proportional hazards in first-line treatment for patients with metastatic colorectal cancer: Systematic review and network meta-analysis

This study aimed to identify the most effective first-line treatment for patients with metastatic colorectal cancer based on overall survival, identify the most commonly used treatment, and generate a meaningful ranking among all available treatments based on their relative effectiveness. Researchers used the ANOVA parametrization method to fit the second-order fractional polynomial network meta-analysis with a random-effect model. Using a non-proportional hazards network meta-analysis, 46 treatments were compared by considering a combination of direct and indirect evidence extracted from clinical trial studies. Included in the review were 46 trials involving 21350 patients. Between January 2000 and January 2023, researchers conducted a thorough search through Embase, PubMed/Medline, and Scopus. To undertake a secondary analysis of this data, we recreate individual patient data from published Kaplan-Meier (K-M) survival curves and assess the accuracy of that reconstruction. A random-effects model was used to evaluate the pooled overall survival and hazard ratio with a 95 percent confidence interval. The predicted survival curves for the network meta-analysis showed that GOLFIG and FOLFOX + Cetuximab treatments have higher survival, respectively. Our results provide moderate quality evidence and comparative effective estimates for various available first-line treatments for metastasis colorectal cancer based on network meta-analysis.

Are Patient-Reported Outcome Measures for Anterior Cruciate Ligament Injuries Validated for Spanish Language and Culture?

Patient-reported outcome measures (PROMs) have been adopted as a way to measure patient self-rated physical function and health status for patients with anterior cruciate ligament (ACL) injuries. Although multiple PROMs exist and have been translated into various languages, the cross-cultural adaptation and validity of these PROMs for Spanish-speaking patients is unknown. To evaluate the adaptation quality and psychometric properties of Spanish-language adaptations of PROMs for patients with ACL injuries. Scoping review; Level of evidence, 3. Under PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, we reviewed published studies related to adaptation quality and psychometric properties of Spanish PROMs in patients with ACL injuries. The methodological quality of the included studies was assessed using the Guidelines for the Process of Cross-Cultural Adaptation of Self-Reported Measures, the Quality Criteria for Psychometric Properties of Health Status Questionnaires, and the Consensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist. The level of evidence for each PROM was determined based on the number of studies, methodological quality, consistency of results, and sample size. The initial search strategy identified 5687 articles. After removal of duplicates, 1882 titles were screened, and 114 articles were assessed for eligibility. Six articles were selected for final review, comprising 4 PROMs: the Lysholm knee score, the Anterior Cruciate Ligament-Return to Sport After Injury (ACL-RSI), the Lower Extremity Functional Scale, and the Lower Limb Functional Index. Three studies followed all 6 processes for cross-cultural adaptation. None of the studies demonstrated all 14 domains required for cross-cultural validity (eg, description of translator expertise). The ACL-RSI achieved the highest level of evidence, with 3 of 9 domains demonstrating moderate evidence. This review identified 4 instruments that have been translated for Spanish-speaking patients with ACL injuries, none of which demonstrated appropriate adaptation or robust psychometric properties. The study highlights the need for improvement in PROMs for Spanish-speaking patients and the potential for mismeasurement and inappropriate application of PROM results in patients with ACL injuries.

ClinGen Hereditary Cardiovascular Disease Gene Curation Expert Panel: Reappraisal of Genes associated with Hypertrophic Cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac condition affecting ~1 in 500 and exhibits marked genetic heterogeneity. Previously published in 2019, 57 HCM-associated genes were curated providing the first systematic evaluation of gene-disease validity. Here we report work by the ClinGen Hereditary Cardiovascular Disorders Gene Curation Expert Panel (HCVD-GCEP) to reappraise the clinical validity of previously curated and new putative HCM genes. The ClinGen systematic gene curation framework was used to re-classify the gene-disease relationships for HCM and related syndromic entities involving left ventricular hypertrophy. Genes previously curated were included if their classification was not definitive, and if the time since curation was >2-3 years. New genes with literature assertions for HCM were included for initial evaluation. Existing genes were curated for new inheritance patterns where evidence existed. Curations were presented on twice monthly calls, with the HCVD-GCEP composed of 29 individuals from 21 institutions across 6 countries. Thirty-one genes were re-curated and an additional 5 new potential HCM-associated genes were curated. Among the re-curated genes, 17 (55%) genes changed classification: 1 limited and 4 disputed (from no known disease relationship), 9 disputed (from limited), and 3 definitive (from moderate). Among these, 3 (10%) genes had a clinically relevant upgrade, including TNNC1, a 9th sarcomere gene with definitive HCM association. With new evidence, two genes were curated for multiple inheritance patterns (TRIM63, disputed for autosomal dominant but moderate for autosomal recessive; ALPK3, strong for autosomal dominant and definitive for recessive). CSRP3 was curated for a semi-dominant mode of inheritance (definitive). Nine (29%) genes were downgraded to disputed, further discouraging clinical reporting of variants in these genes. Five genes recently reported to cause HCM were curated: RPS6KB1 and RBM20 (limited), KLHL24 and MT-TI (moderate), and FHOD3 (definitive). We report 29 genes with definitive, strong or moderate evidence of causation for HCM or isolated LVH, including sarcomere, sarcomere-associated and syndromic conditions.

IMPACT OF REAL-LIFE ENVIRONMENTAL EXPOSURES ON REPRODUCTION: Evidence for reproductive health effects following exposure to hydraulic fracturing chemical mixtures.

Unconventional oil and natural gas (UOG) operations, particularly hydraulic fracturing, have revolutionized oil and gas production, using and containing complex mixtures of chemicals that may impact reproductive health. While there is growing evidence for effects on births in hydraulic fracturing/UOG regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about these practices and reproductive health. Unconventional oil and natural gas (UOG) operations have emerged over the last four decades to transform oil and gas production in the United States and globally by unlocking previously inaccessible hydrocarbon deposits. UOG development utilizes many compounds associated with conventional oil and gas, as well as some specific to UOG extraction, particularly during hydraulic fracturing (HF). While research is increasing on UOG chemicals and their mixtures, this review discusses the current evidence for reproductive toxicity following exposures to UOG/HF mixtures. These complex chemical mixtures have been demonstrated to interact with numerous mechanisms known to influence reproductive health. A growing number of environmental and controlled laboratory testing studies have reported adverse reproductive health effects in animals exposed to various UOG chemical mixtures. An expanding body of epidemiological literature has assessed adverse birth outcomes, although none has directly examined reproductive measures such as time to pregnancy, semen quality, and other direct measures of fertility. The existing literature provides moderate evidence for decreased birth weights, increased risk of small for gestational age and/or preterm birth, increased congenital abnormalities, and increased infant mortality, though importantly, studies are widely variable in methods used. Most studies utilized distance from UOG operations as an exposure proxy and did not measure actual chemical exposures experienced by those living near these operations. As such, while there is growing evidence for effects on births in these regions and good mechanistic evidence for potential reproductive toxicity, there is much research still needed to make firm conclusions about UOG development and reproductive health.

A certain future strengthens the past: Knowing ahead how to act on an object prioritizes its visual working memory representation.

Findings from recent studies indicate that planning an action toward an object strengthens its visual working memory (VWM) representation, emphasizing the importance of sensorimotor links in VWM. In the present study, we investigated to what extent such sensorimotor links are modulated by how well-defined an action plan is. In three eye-tracking experiments, we asked participants to memorize a visual stimulus for a subsequent memory test, whereby they performed a specific hand movement toward memory-matching probes. We manipulated action uncertainty so that in the defined action condition, participants knew before the memory delay what specific action they would have to perform at the memory test, while in the undefined action condition, they were informed about the specific action on the object in VWM only after the delay. Importantly, during the delay, participants were presented with a visual detection task, designed to measure any attentional biases toward the memorized object. Across the three experiments, we found moderate evidence that knowing in advance how to act on an object prioritized its mnemonic representation, as expressed in an increased attentional bias toward it. Our results support the idea that knowing what action to perform on an object strengthens its representation in VWM, and further highlight the importance of considering action in the study of VWM. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Assessment of the evidence yield for the calibrated PP3/BP4 computational recommendations

Purpose: To investigate the number of rare missense variants observed in human genome sequences by ACMG/AMP PP3/BP4 evidence strength, following the ClinGen-calibrated PP3/BP4 computational recommendations. MethodsMissense variants from the genome sequences of 300 probands from the Rare Genomes Project with suspected rare disease were analyzed using computational prediction tools that were able to reach PP3_Strong and BP4_Moderate evidence strengths (BayesDel, MutPred2, REVEL, and VEST4). The numbers of variants at each evidence strength were analyzed across disease-associated genes and genome-wide. ResultsFrom a median of 75.5 rare (≤1% allele frequency) missense variants in disease-associated genes per proband, a median of one reached PP3_Strong, 3-5 PP3_Moderate, and 3-5 PP3_Supporting. Most were allocated BP4 evidence (median 41-49 per proband) or were indeterminate (median 17.5-19 per proband). Extending the analysis to all protein-coding genes genome-wide, the number of variants reaching PP3_Strong score thresholds increased approximately 2.6-fold compared with disease-associated genes, with a median per proband of 1-3 PP3_Strong, 8-16 PP3_Moderate, and 10-17 PP3_Supporting. ConclusionA small number of variants per proband reached PP3_Strong and PP3_Moderate in 3424 disease-associated genes. Although not the intended use of the recommendations, this was also observed genome-wide. Use of PP3/BP4 evidence as recommended from calibrated computational prediction tools in the clinical diagnostic laboratory is unlikely to inappropriately contribute to the classification of an excessive number of variants as pathogenic or likely pathogenic by ACMG/AMP rules.

European Headache Federation (EHF) critical re-appraisal and meta-analysis of oral drugs in migraine prevention - part 4: propranolol

ObjectiveThe aim of this paper is to critically re-appraise the published trials assessing propranolol for migraine prophylaxis.MethodsWe report methods and results following the Preferred Reporting Items for Systematic Reviews (PRISMA), by searching MEDLINE, EMBASE, Cochrane CENTRAL, and ClinicalTrials.gov for randomized trials of pharmacologic treatments for migraine prophylaxis. We included randomized trials that compared propranolol with placebo for migraine prophylaxis in adults. The outcomes of interest were informed by the Core outcome set for preventive intervention trials in chronic and episodic migraine (COSMIG) and include the proportion of patients who experience a 50% or more reduction in monthly migraine days, the reduction of monthly migraine days, and the number of adverse events leading to discontinuation. We assessed risk of bias by using a modified Cochrane RoB (risk of bias) 2.0 tool and the certainty of evidence by using the GRADE approach.ResultsOur search yielded twenty trials (n = 1291 patients) eligible for data synthesis and analysis. The analysis revealed a moderate certainty evidence that propranolol leads to a reduction in monthly migraine days versus placebo (-1.27; 95% CI: -2.25 to -0.3). We found moderate certainty evidence that propranolol increases the proportion of patients who experience a 50% or more reduction in monthly migraine days, compared to placebo with a relative risk of 1.65 (95% CI 1.41 to 1.93); absolute risk difference: 179 more per 1,000 (95% CI 113 to 256). We found high certainty evidence that propranolol increases the proportion of patients who discontinue due to adverse events compared to placebo with a risk difference of 0.02 (95% CI 0.00 to 0.03); absolute risk difference: 20 more per 1,000 (95% CI 0 to 30).ConclusionsThe present meta-analysis shows that propranolol has a prophylactic role in migraine, with an overall acceptable tolerability profile. Combining these results with its long-standing use and its global availability at a low cost confirms its role as a first line agent in the prophylaxis of migraine.

A Bayesian Study of Drinking and Intimate Partner Violence Across Two- and Four-Year Colleges

ABSTRACT This study investigated intimate partner violence victimization patterns in two-year and four-year college students, examining heavy episodic drinking as a risk factor. Using Bayesian analysis to assess similarities, Hypothesis 1 found moderate evidence for no reliable differences in dating victimization between groups. Hypothesis 2 indicated that heavy episodic drinking reliably predicted intimate partner violence in both college types. Contrary to Hypothesis 3, the relationship strength between heavy episodic drinking and intimate partner violence did not differ between campus types. These results suggest consistent intimate partner violence patterns across college types, emphasizing the importance of addressing heavy episodic drinking in prevention efforts for both groups. The study contributes valuable insights to understanding and mitigating intimate partner violence risks in diverse college settings.

Effects of app-based relaxation techniques on perceived momentary relaxation: Observational data analysis in people with cancer

ObjectiveTo examine the effects of six relaxation techniques on perceived momentary relaxation and a possible association of relaxation effects with time and practice experience in people with cancer. MethodsWe used data from participants with cancer in a larger study practicing app-based relaxation techniques over 10 weeks, assessed momentary relaxation before and after every third relaxation practice, and analyzed momentary relaxation changes with a linear mixed-effects model. ResultsThe sample included 611 before-after observations from 91 participants (70 females (76.9%)) with a mean age of 55.43 years (SD 10.88). We found moderate evidence for variations in momentary relaxation changes across different techniques (P = .026), with short meditation, mindfulness meditation, guided imagery, and progressive muscle relaxation more frequently observed and leading to more relaxation than body scan and walking meditation. Furthermore, we found moderate evidence for increasing momentary relaxation changes over time (P = .046), but no evidence for an association between momentary relaxation and the number of previous observations (proxy for practice experience; P = .47). ConclusionWe compared six app-based relaxation techniques in a real-life setting of people with cancer. The observed variations in perceived momentary relaxation appear to correspond with the popularity of the techniques used: The most popular relaxation techniques were the most effective and the least popular were the least effective. The effects increased over time, likely caused by dropout of individuals who gained no immediate benefit. Our findings open an interesting avenue for future research to better understand which relaxation techniques work best for whom in which situations. Trial RegistrationDRKS00027546; https://drks.de/search/en/trial/DRKS00027546

Small-volume blood sample collection tubes in adult intensive care units: A rapid practice guideline.

This Intensive Care Medicine Rapid Practice Guideline (ICM-RPG) provides an evidence-based recommendation to address the question: in adult patients in intensive care units (ICUs), should we use small-volume or conventional blood collection tubes? We included 23 panelists in 8 countries and assessed and managed financial and intellectual conflicts of interest. Methodological support was provided by the Guidelines in Intensive Care, Development, and Evaluation (GUIDE) group. We conducted a systematic review, including evidence from observational and randomized studies. Using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) approach, we evaluated the certainty of evidence and developed recommendations using the Evidence-to-Decision framework. We identified 8 studies (1 cluster and 2 patient-level randomized trials; 5 observational studies) comparing small-volume to conventional tubes. We had high certainty evidence that small-volume tubes reduce daily and cumulative blood sampling volume; and moderate certainty evidence that they reduce the risk of transfusion and mean number of red blood cell units transfused, but these estimates were limited by imprecision. We had high certainty that small-volume tubes have a similar rate of specimens with insufficient quantity. The panel considered that the desirable effects of small-volume tubes outweigh the undesirable effects, are less wasteful of resources, and are feasible, as demonstrated by successful implementation across multiple countries, although there are upfront implementation costs to validate small-volume tubes on laboratory instrumentation. This ICM-RPG panel made a strong recommendation for the use of small-volume sample collection tubes in adult ICUs based on overall moderate certainty evidence.

Efficacy of daily versus intermittent oral iron supplementation for prevention of anaemia among pregnant women: a systematic review and meta-analysis

The World Health Organization recommends daily oral supplementation of iron for prevention of maternal anaemia. However, the adverse effects due to daily supplementation leads to poor compliance among pregnant women. Also, the mucosal block theory suggests that intermittent oral iron may be more efficient than daily iron with respect to optimum absorption. Our meta-analysis reviewed the existing clinical studies for the efficacy of daily versus intermittent oral iron supplementation. In this systematic review and meta-analysis [PROSPERO ID:CRD42024498180], we searched PubMed, Google Scholar, Scopus, Science Direct and Cochrane database for studies published from 1st January 1970 to 31st December, 2023. Studies comparing daily and intermittent iron supplementation in pregnant women were included. The median intermittent iron dose was 120mg/day and daily iron dose was 60mg/day. The primary outcome was endpoint haemoglobin levels after iron supplementation. The data was analysed using the 'meta' and 'metafor' packages in RStudio using random effects model. The heterogeneity, publication bias, risk of bias and certainty of evidence were assessed using I2 statistics, funnel plots, Cochrane Risk of Bias 2 (ROB2) tool, and the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach respectively. Of 4615 search results, 26 studies (n=4365 participants) were included in this meta-analysis. There was no significant difference (p=0.18) between the endpoint mean haemoglobin levels of the daily versus intermittent oral iron groups (standardized mean difference (SMD): 0.51, 95% CI:-0.23 to 1.24, I2=97%, low certainty evidence) irrespective of baseline anaemic status. However, the endpoint ferritin levels were significantly higher in the daily supplementation group (SMD: 0.85, 95% CI: 0.15-1.54, p=0.02, I2=97%, low certainty evidence). The adjusted odds ratio for nausea, (adjusted odds ratio (OR) 3.56, 95% CI: 2.23-5.69, p<0.001, I2=9%, moderate certainty evidence), diarrhoea (adjusted OR 5.40, 95% CI: 1.90-15.33, p=0.002, I2=0%, low certainty evidence) and constipation (adjusted OR 1.95, 95% CI: 1.21-3.14, p=0.006, I2=0%, moderate certainty evidence) was significantly higher in daily oral iron supplementation group. Intermittent oral iron supplementation with a median dose of 120mg/day demonstrates comparable efficacy to daily oral iron supplementation median dose of 60mg/day in increasing haemoglobin levels among pregnant women with a significant reduction in adverse events. There was no funding for this study.