Impaired ketogenesis ties metabolism to T cell dysfunction in COVID-19.

Anorexia and fasting are host adaptations to acute infection, and induce a metabolic switch towards ketogenesis and the production of ketone bodies, including ß-hydroxybutyrate (BHB)1-6. However, whether ketogenesis metabolically influences the immune response in pulmonary infections remains unclear. Here we show that the production of BHB is impaired in individuals with SARS-CoV-2-induced acute respiratory distress syndrome (ARDS) but not in those with  influenza-induced ARDS. We found that BHB promotes both the survival of and the production of interferon-γ by CD4+ T cells. Applying a metabolic-tracing analysis, we established that BHB provides an alternative carbon source to fuel oxidative phosphorylation (OXPHOS) and the production of bioenergetic amino acids and glutathione, which is important for maintaining the redox balance. T cells from patients with SARS-CoV-2-induced ARDS were exhausted and skewed towards glycolysis, but could be metabolically reprogrammed by BHB to perform OXPHOS, thereby increasing their functionality. Finally, we show in mice that a ketogenic diet and the delivery of BHB as a ketone ester drink restores CD4+ T cell metabolism and function in severe respiratory infections, ultimately reducing the mortality of mice infected with SARS-CoV-2. Altogether, our data reveal that BHB is an alternative source of carbon that promotes T cell responses in pulmonary viral infections, and highlight impaired ketogenesis as a potential confounding factor in severe COVID-19.

The effect of micronutrient supplementation on serum anti-Mullerian hormone levels: a retrospective pilot study.

BACKGROUND: The anti-Müllerian-hormone (AMH) is secreted by the granulosa cells of the oocytes and can be used as a marker of the ovarian reserve; helpful to estimate female fertility or the menopause onset. Although various factors may influence AMH levels, the correlation with nutritional factors needs more research. OBJECTIVE: To evaluate the effect of a micronutrient supplementation on female AMH levels. METHODS: This retrospective analysis includes a total of 244 women, who attended the Karl Landsteiner Institute, Korneuburg, Austria from January 2013 to June 2019 due to an unfulfilled desire for a child. All women were treated with an oral micronutrient preparation consisting the dosage of one soft capsule and one tablet per day for 3 months. The soft capsule contains omega-3 fatty acids and the tablet is a standardized combination of coenzyme Q10, vitamin E, folic acid, selenium, catechins from green tea extract, and glycyrrhizin from licorice extract. Serum AMH levels before and after 3 months were compared. In addition, available clinical data such as ovulation frequency, endometrium thickness, and luteal phase duration were analyzed. RESULTS: The mean age of the women was 37.3 ± 1.8 years, the mean body mass index of 24.3 ± 4.6 k/m2. The mean serum AMH levels and endometrial thickness values were significantly higher after micronutrient supplementation as compared to baseline (1.42 ± 0.86 versus 1.86 ± 0.82 ng/mL and 6.10 ± 1.76 versus 7.29 ± 1.65 mm, respectively). In addition, ovulation frequency and luteal phase duration significantly improved in more than 60%. CONCLUSION: Proposed micronutrient supplementation had a positive effect on serum AMH levels, endometrial thickness, ovulation frequency, and luteal phase duration. It could be a simple, risk-free therapeutic option to improve female fertility. More research is warranted to prove this effect.

Does evidence support "banking/extending sleep" by shift workers to mitigate fatigue, and/or to improve health, safety, or performance? A systematic review.

BACKGROUND: Sleep deprivation is common in shift work occupations, including safety-sensitive occupations. While extending sleep prior to scheduled shifts (i.e., "banking sleep") may be an intuitive strategy for fatigue mitigation, the evidence behind this strategy is unclear. METHODS: We performed a systematic review of literature retrieved in searches of four databases. We examined agreement between two independent screeners, abstracted key findings, reviewed and synthesized findings, and evaluated the quality of evidence using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. The Cochrane Collaboration's risk of bias tool was used to evaluate bias of individual studies. We reported findings as prescribed by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Of the 3007 records screened, five met inclusion criteria. The inter-rater agreement for inclusion/exclusion was high (κ = 0.87). One study addressed patient safety outcomes. Four studies assessed the impact of banking sleep on performance, five assessed measures of acute fatigue, and three evaluated banking sleep on indicators of health. All five studies presented a very serious risk of bias and the quality of evidence was very low. Given these caveats, the findings, in aggregate, support banking sleep as a strategy to improve indicators of performance and acute fatigue. CONCLUSIONS: This systematic review identifies gaps in research of shift workers on the efficacy of banking sleep as a fatigue risk management strategy. The available evidence supports banking sleep prior to shiftwork as a strategy for improved patient safety, performance, and reducing acute fatigue.

Impact of lifestyle modification on absolute cardiovascular disease risk: a systematic review protocol.

OBJECTIVE: The objective of this review is to synthesize the available evidence on the effectiveness of lifestyle-based interventions for reducing absolute cardiovascular disease (CVD). INTRODUCTION: Cardiovascular disease prevention guidelines recommend tailoring the choice and intensity of preventive interventions based on absolute CVD risk score. Several studies employing lifestyle-based interventions to mitigate CVD risk have reported heterogeneous outcomes, necessitating a systematic review to provide an exhaustive summary of current evidence. INCLUSION CRITERIA: Eligible studies will include individuals at high-risk of CVD who are at least 18 years of age, with no history of CVD at baseline, regardless of sex, ethnicity and socio-economic status. Studies that compare lifestyle-based intervention to no intervention or usual care will be included. The outcome of interest is change in absolute CVD risk from baseline to post-intervention. Experimental and quasi-experimental study designs will be included. METHODS: Searches will be conducted in PubMed, EMBASE and CINAHL from the inception of each database. The search for gray literature will include ProQuest Dissertations and Theses Global, Grey Literature Report, Web of Science, BIOSIS Previews and the Proceedings database. Selected studies will be critically appraised by two independent reviewers at the study level for methodological quality. Extracted data will include details about the interventions, populations, study methods and outcomes of significance to the review question and objectives. Where possible, papers will be pooled in statistical meta-analysis. Effect sizes will be expressed as either odds ratios or standardized mean differences, and their 95% confidence intervals will be calculated for analysis. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42017073543.

Effect of insomnia treatments on depression: A systematic review and meta-analysis.

BACKGROUND: Insomnia is frequently co-morbid with depression, with a bidirectional relationship between these disorders. There is evidence that insomnia-specific interventions, such as cognitive behavioral therapy for insomnia, may lead to improvements in depression. The purpose of this systematic review and meta-analysis is to determine whether treatment of insomnia leads to improved depression outcomes in individuals with both insomnia and depression. METHODS: We conduct a systematic review and meta-analysis to explore the effect of treatment for insomnia disorder on depression in patients with both disorders. RESULTS: Three thousand eight hundred and fifteen studies were reviewed, and 23 studies met inclusion criteria. Although all of the studies suggested a positive clinical effect of insomnia treatment on depression outcomes, most of the results were not statistically significant. Although the interventions and populations were highly variable, the meta-analysis indicates moderate to large effect size (ES) improvement in depression as measured with the Hamilton Depression Rating Scale (ES = -1.29, 95%CI [-2.11, -0.47]) and Beck Depression Inventory (ES = -0.68, 95%CI [-1.29, -0.06]). CONCLUSIONS: These results support that treating insomnia in patients with depression has a positive effect on mood. Future trials are needed to identify the subtypes of patients whose depression improves during treatment with insomnia-specific interventions, and to identify the mechanisms by which treating insomnia improves mood.

Evaluation and management of traumatic diaphragmatic injuries: A Practice Management Guideline from the Eastern Association for the Surgery of Trauma.

BACKGROUND: Traumatic diaphragm injuries (TDI) pose both diagnostic and therapeutic challenges in both the acute and chronic phases. There are no published practice management guidelines to date for TDI. We aim to formulate a practice management guideline for TDI using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology. METHODS: The working group formulated five Patient, Intervention, Comparator, Outcome questions regarding the following topics: (1) diagnostic approach (laparoscopy vs. computed tomography); (2) nonoperative management of penetrating right-sided injuries; (3) surgical approach (abdominal or thoracic) for acute TDI, including (4) the use of laparoscopy; and (5) surgical approach (abdominal or thoracic) for delayed TDI. A systematic review was undertaken and last updated December 2016. RevMan 5 (Cochran Collaboration) and GRADEpro (Grade Working Group) software were used. Recommendations were voted on by working group members. Consensus was obtained for each recommendation. RESULTS: A total of 56 articles were used to formulate the recommendations. Most studies were retrospective case series with variable reporting of outcomes measures and outcomes frequently not stratified to intervention or comparator. The overall quality of the evidence was very low for all Patient, Intervention, Comparator, Outcomes. Therefore, only conditional recommendations could be made. CONCLUSION: Recommendations were made in favor of laparoscopy over computed tomography for diagnosis, nonoperative versus operative approach for right-sided penetrating injuries, abdominal versus thoracic approach for acute TDI, and laparoscopy (with the appropriate skill set and resources) versus open approach for isolated TDI. No recommendation could be made for the preferred operative approach for delayed TDI. Very low-quality evidence precluded any strong recommendations. Further study of the diagnostic and therapeutic approaches to TDI is warranted. LEVEL OF EVIDENCE: Guideline; Systematic review, level IV.

Systematic Review Methodology for the Fatigue in Emergency Medical Services Project.

BACKGROUND: Guidance for managing fatigue in the Emergency Medical Services (EMS) setting is limited. The Fatigue in EMS Project sought to complete multiple systematic reviews guided by seven explicit research questions, assemble the best available evidence, and rate the quality of that evidence for purposes of producing an Evidence Based Guideline (EBG) for fatigue risk management in EMS operations. METHODS: We completed seven systematic reviews that involved searches of six databases for literature relevant to seven research questions. These questions were developed a priori by an expert panel and framed in the Population, Intervention, Comparison, and Outcome (PICO) format and pre-registered with PROSPERO. Our target population was defined as persons 18 years of age and older classified as EMS personnel or similar shift worker groups. A panel of experts selected outcomes for each PICO question as prescribed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We pooled findings, stratified by study design (experimental vs. observational) and presented results of each systematic review in narrative and quantitative form. We used meta-analyses of select outcomes to generate pooled effects. We used the GRADE methodology and the GRADEpro software to designate a quality of evidence rating for each outcome. RESULTS: We present the results for each systematic review in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). More than 38,000 records were screened across seven systematic reviews. The median, minimum, and maximum inter-rater agreements (Kappa) between screeners for our seven systematic reviews were 0.66, 0.49, and 0.88, respectively. The median, minimum, and maximum number of records retained for the seven systematic reviews was 13, 1, and 100, respectively. We present key findings in GRADE Evidence Profile Tables in separate publications for each systematic review. CONCLUSIONS: We describe a protocol for conducting multiple, simultaneous systematic reviews connected to fatigue with the goal of creating an EBG for fatigue risk management in the EMS setting. Our approach may be informative to others challenged with the creation of EBGs that address multiple, inter-related systematic reviews with overlapping outcomes.

Effect of Fatigue Training on Safety, Fatigue, and Sleep in Emergency Medical Services Personnel and Other Shift Workers: A Systematic Review and Meta-Analysis.

BACKGROUND: Fatigue training may be an effective way to mitigate fatigue-related risk. We aimed to critically review and synthesize existing literature on the impact of fatigue training on fatigue-related outcomes for Emergency Medical Services (EMS) personnel and similar shift worker groups. METHODS: We performed a systematic literature review for studies that tested the impact of fatigue training of EMS personnel or similar shift workers. Outcomes of interest included personnel safety, patient safety, personnel performance, acute fatigue, indicators of sleep duration and quality, indicators of long-term health (e.g., cardiovascular disease), and burnout/stress. A meta-analysis was performed to determine the impact of fatigue training on sleep quality. RESULTS: Of the 3,817 records initially identified for review, 18 studies were relevant and examined fatigue training in shift workers using an experimental or quasi-experimental design. Fatigue training improved patient safety, personal safety, and ratings of acute fatigue and reduced stress and burnout. A meta-analysis of five studies showed improvement in sleep quality (Fixed Effects SMD -0.87; 95% CI -1.05 to -0.69; p < 0.00001; Random Effects SMD -0.80; 95% CI -1.72, 0.12; p < 0.00001). CONCLUSIONS: Reviewed literature indicated that fatigue training improved safety and health outcomes in shift workers. Further research is required to identify the optimal components of fatigue training programs to maximize the beneficial outcomes.

Systematic Review and Meta-analysis of the Effects of Caffeine in Fatigued Shift Workers: Implications for Emergency Medical Services Personnel.

BACKGROUND: Emergency Medical Services (EMS) workers may experience fatigue as a consequence of shift work. We reviewed the literature to determine the impact of caffeine as a countermeasure to fatigue in EMS personnel and related shift workers. METHODS: We employed the GRADE methodology to perform a systematic literature review and search multiple databases for research that examined the impact of caffeine on outcomes of interest, such as patient and EMS personnel safety. For selected outcomes, we performed a meta-analysis of pooled data and reported the pooled effect in the form of a Standardized Mean Difference (SMD) with corresponding 95% confidence intervals. RESULTS: There are no studies that investigate caffeine use and its effects on EMS workers or on patient safety. Four of 8 studies in shift workers showed that caffeine improved psychomotor vigilance, which is important for performance. Caffeine decreased the number of lapses on a standardized test of performance [SMD = 0.75 (95% CI: 0.30 to 1.19), p = 0.001], and lessened the slowing of reaction time at the end of shifts [SMD = 0.52 (95% CI: 0.19 to 0.85); p = 0.002]. Finally, 2 studies reported that caffeine reduced sleep quality and sleep duration. CONCLUSIONS: Although the quality of evidence was judged to be low to moderate, when taken together, these studies demonstrate that caffeine can improve psychomotor performance and vigilance. However, caffeine negatively affects sleep quality and sleep duration. More systematic, randomized studies need to be conducted in EMS workers in order to address the critical outcomes of health and safety of EMS personnel and patients. The risk/benefit ratio of chronic caffeine use in shift workers is currently unknown.

Reliability and Validity of Survey Instruments to Measure Work-Related Fatigue in the Emergency Medical Services Setting: A Systematic Review.

BACKGROUND: This study sought to systematically search the literature to identify reliable and valid survey instruments for fatigue measurement in the Emergency Medical Services (EMS) occupational setting. METHODS: A systematic review study design was used and searched six databases, including one website. The research question guiding the search was developed a priori and registered with the PROSPERO database of systematic reviews: "Are there reliable and valid instruments for measuring fatigue among EMS personnel?" (2016:CRD42016040097). The primary outcome of interest was criterion-related validity. Important outcomes of interest included reliability (e.g., internal consistency), and indicators of sensitivity and specificity. Members of the research team independently screened records from the databases. Full-text articles were evaluated by adapting the Bolster and Rourke system for categorizing findings of systematic reviews, and the rated data abstracted from the body of literature as favorable, unfavorable, mixed/inconclusive, or no impact. The Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology was used to evaluate the quality of evidence. RESULTS: The search strategy yielded 1,257 unique records. Thirty-four unique experimental and non-experimental studies were determined relevant following full-text review. Nineteen studies reported on the reliability and/or validity of ten different fatigue survey instruments. Eighteen different studies evaluated the reliability and/or validity of four different sleepiness survey instruments. None of the retained studies reported sensitivity or specificity. Evidence quality was rated as very low across all outcomes. CONCLUSIONS: In this systematic review, limited evidence of the reliability and validity of 14 different survey instruments to assess the fatigue and/or sleepiness status of EMS personnel and related shift worker groups was identified.

Does Implementation of Biomathematical Models Mitigate Fatigue and Fatigue-related Risks in Emergency Medical Services Operations? A Systematic Review.

BACKGROUND: Work schedules like those of Emergency Medical Services (EMS) personnel have been associated with increased risk of fatigue-related impairment. Biomathematical modeling is a means of objectively estimating the potential impacts of fatigue on performance, which may be used in the mitigation of fatigue-related safety risks. In the context of EMS operations, our objective was to assess the evidence in the literature regarding the effectiveness of using biomathematical models to help mitigate fatigue and fatigue-related risks. METHODS: A systematic review of the evidence evaluating the use of biomathematical models to manage fatigue in EMS personnel or similar shift workers was performed. Procedures proposed by the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology were used to summarize and rate the certainty in the evidence. Potential bias attached to retained studies was documented using the Cochrane Collaboration's Risk of Bias tool for experimental studies. RESULTS: The literature search strategy, which focused on both EMS personnel and non-EMS shift workers, yielded n = 2,777 unique records. One paper, which investigated non-EMS shift workers, met inclusion criteria. As part of a larger effort, managers and dispatchers of a trucking operation were provided with monthly biomathematical model analyses of predicted fatigue in the driver workforce, and educated on how they could reduce predicted fatigue by means of schedule adjustments. The intervention showed a significant reduction in the number and cost of vehicular accidents during the period in which biomathematical modeling was used. The overall GRADE assessment of evidence quality was very low due to risk of bias, indirectness, imprecision, and publication bias. CONCLUSIONS: This systematic review identified no studies that investigated the impact of biomathematical models in EMS operations. Findings from one study of non-EMS shift workers were favorable toward use of biomathematical models as a fatigue mitigation scheduling aid, albeit with very low quality of evidence pertaining to EMS operations. We propose three focus areas of research priorities that, if addressed, could help better elucidate the utility and impact of biomathematical models as a fatigue-mitigation tool in the EMS environment.

Effect of Task Load Interventions on Fatigue in Emergency Medical Services Personnel and Other Shift Workers: A Systematic Review.

BACKGROUND: Modifying the task load of Emergency Medical Services (EMS) personnel may mitigate fatigue, sleep quality and fatigue related risks. A review of the literature addressing task load interventions may benefit EMS administrators as they craft policies related to mitigating fatigue. We conducted a systematic review of the peer-reviewed literature to address the following question: "In EMS personnel, do task load interventions mitigate fatigue, mitigate fatigue-related risks, and/or improve sleep?" (PROSPERO 2016:CRD42016040114). METHODS: We performed a systematic review of the literature that described use of randomized controlled trials, quasi-experimental studies, and observational study designs. We retained and reviewed research that involved EMS personnel or similar shift worker groups 18 years of age and older. Studies of 'healthy volunteers' and non-shift worker populations were excluded. Studies were included where the methodology of the study implied a theoretical framework of task load (or workload) affecting fatigue, and then fatigue related outcomes. Outcomes of interest included personnel safety, patient safety, personnel performance, acute fatigue, and cost to system. We used the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology to summarize findings and assess quality of evidence from very low to high quality. RESULTS: The search strategy yielded 3,394 unique records resulting in 58 records included as potentially eligible. An additional 69 studies were reviewed in full following searches of bibliographies. We detected wide variation in the description and measurement of task load in the retained and excluded research. Among 127 potentially relevant studies reviewed in full, five were judged eligible. None of the retained studies reported findings germane to personnel safety, patient safety, or cost to system. We judged most studies to have serious or very serious risk of bias. CONCLUSIONS: The effect of task load interventions on fatigue, fatigue-related risks, and/or sleep quality was not estimable and the overall quality of evidence was judged low or very low. There was considerable heterogeneity in how task load was defined and measured.

Shorter Versus Longer Shift Durations to Mitigate Fatigue and Fatigue-Related Risks in Emergency Medical Services Personnel and Related Shift Workers: A Systematic Review.

BACKGROUND: This study comprehensively reviewed the literature on the impact of shorter versus longer shifts on critical and important outcomes for Emergency Medical Services (EMS) personnel and related shift worker groups. METHODS: Six databases (e.g., PubMed/MEDLINE) were searched, including one website. This search was guided by a research question developed by an expert panel a priori and registered with the PROSPERO database of systematic reviews (2016:CRD42016040099). The critical outcomes of interest were patient safety and personnel safety. The important outcomes of interest were personnel performance, acute fatigue, sleep and sleep quality, retention/turnover, long-term health, burnout/stress, and cost to system. Screeners worked independently and full-text articles were assessed for relevance. Data abstracted from the retained literature were categorized as favorable, unfavorable, mixed/inconclusive, or no impact toward the shorter shift duration. This research characterized the evidence as very low, low, moderate, or high quality according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: The searched yielded n = 21,674 records. Of the 480 full-text articles reviewed, 100 reported comparisons of outcomes of interest by shift duration. We identified 24 different shift duration comparisons, most commonly 8 hours versus 12 hours. No one study reported findings for all 9 outcomes. Two studies reported findings linked to both critical outcomes of patient and personnel safety, 34 reported findings for one of two critical outcomes, and 64 did not report findings for critical outcomes. Fifteen studies were grouped to compare shifts <24 hours versus shifts ≥24 hours. None of the findings for the critical outcomes of patient and personnel safety were categorized as unfavorable toward shorter duration shifts (<24 hours). Nine studies were favorable toward shifts <24 hours for at least one of the 7 important outcomes, while findings from one study were categorized as unfavorable. Evidence quality was low or very low. CONCLUSIONS: The quality of existing evidence on the impact of shift duration on fatigue and fatigue-related risks is low or very low. Despite these limitations, this systematic review suggests that for outcomes considered critical or important to EMS personnel, shifts <24 hours in duration are more favorable than shifts ≥24 hours.

Effects of Napping During Shift Work on Sleepiness and Performance in Emergency Medical Services Personnel and Similar Shift Workers: A Systematic Review and Meta-Analysis.

BACKGROUND: Scheduled napping during work shifts may be an effective way to mitigate fatigue-related risk. This study aimed to critically review and synthesize existing literature on the impact of scheduled naps on fatigue-related outcomes for EMS personnel and similar shift worker groups. METHODS: A systematic literature review was performed of the impact of a scheduled nap during shift work on EMS personnel or similar shift workers. The primary (critical) outcome of interest was EMS personnel safety. Secondary (important) outcomes were patient safety; personnel performance; acute states of fatigue, alertness, and sleepiness; indicators of sleep duration and/or quality; employee retention/turnover; indicators of long-term health; and cost to the system. Meta-analyses were performed to evaluate the impact of napping on a measure of personnel performance (the psychomotor vigilance test [PVT]) and measures of acute fatigue. RESULTS: Of 4,660 unique records identified, 13 experimental studies were determined relevant and summarized. The effect of napping on reaction time measured at the end of shift was small and non-significant (SMD 0.12, 95% CI -0.13 to 0.36; p = 0.34). Napping during work did not change reaction time from the beginning to the end of the shift (SMD -0.01, 95% CI -25.0 to 0.24; p = 0.96). Naps had a moderate, significant effect on sleepiness measured at the end of shift (SMD 0.40, 95% CI 0.09 to 0.72; p = 0.01). The difference in sleepiness from the start to the end of shift was moderate and statistically significant (SMD 0.41, 95% CI 0.09 to 0.72; p = 0.01). CONCLUSIONS: Reviewed literature indicated that scheduled naps at work improved performance and decreased fatigue in shift workers. Further research is required to identify the optimal timing and duration of scheduled naps to maximize the beneficial outcomes.

An investigation into quality of life improvement in patients undergoing microvascular decompression for hemifacial spasm.

OBJECTIVE Hemifacial spasm (HFS) is a movement disorder characterized by involuntary spasms of the facial muscles, and it can negatively impact quality of life (QOL). This retrospective study and systematic review with meta-analysis was conducted to investigate the QOL in patients with HFS following intervention with microvascular decompression (MVD) and botulinum toxin (BT). METHODS In the retrospective analysis, a QOL questionnaire was administered to all patients undergoing MVD performed by a single surgeon. The QOL questionnaire included unique questions developed based on the authors' experience with HFS patients in addition to the health-related QOL HFS-8 questionnaire. The authors also report on a systematic review of the English literature providing outcomes and complications in patients with HFS undergoing treatment with either MVD or BT. RESULTS Regarding the retrospective analysis, 242 of 331 patients completed the questionnaire. The mean score of the 10 QOL questions improved from 22.78 (SD 9.83) to 2.17 (SD 5.75) following MVD (p < 0.001). There was significant improvement across all subscales of the questionnaire between pre- and postoperative responses (p < 0.001). Regarding the systematic review, it is reported that approximately 90% of patients undergoing MVD for HFS experience a complete recovery from symptoms, whereas the mean peak improvement of symptoms following treatment with BT is 77%. Furthermore, patients undergoing MVD reported a greater improvement in the mean supplemental index of QOL as compared with patients receiving BT therapy. CONCLUSIONS Microvascular decompression offers a significant improvement in QOL in well-selected patients suffering from HFS, and may offer an increased benefit for QOL over BT injections.

Evidence-Based Guidelines for Fatigue Risk Management in EMS: Formulating Research Questions and Selecting Outcomes.

BACKGROUND: Greater than half of Emergency Medical Services (EMS) personnel report work-related fatigue, yet there are no guidelines for the management of fatigue in EMS. A novel process has been established for evidence-based guideline (EBG) development germane to clinical EMS questions. This process has not yet been applied to operational EMS questions like fatigue risk management. The objective of this study was to develop content valid research questions in the Population, Intervention, Comparison, and Outcome (PICO) framework, and select outcomes to guide systematic reviews and development of EBGs for EMS fatigue risk management. METHODS: We adopted the National Prehospital EBG Model Process and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework for developing, implementing, and evaluating EBGs in the prehospital care setting. In accordance with steps one and two of the Model Process, we searched for existing EBGs, developed a multi-disciplinary expert panel and received external input. Panelists completed an iterative process to formulate research questions. We used the Content Validity Index (CVI) to score relevance and clarity of candidate PICO questions. The panel completed multiple rounds of question editing and used a CVI benchmark of ≥0.78 to indicate acceptable levels of clarity and relevance. Outcomes for each PICO question were rated from 1 = less important to 9 = critical. RESULTS: Panelists formulated 13 candidate PICO questions, of which 6 were eliminated or merged with other questions. Panelists reached consensus on seven PICO questions (n = 1 diagnosis and n = 6 intervention). Final CVI scores of relevance ranged from 0.81 to 1.00. Final CVI scores of clarity ranged from 0.88 to 1.00. The mean number of outcomes rated as critical, important, and less important by PICO question was 0.7 (SD 0.7), 5.4 (SD 1.4), and 3.6 (SD 1.9), respectively. Patient and personnel safety were rated as critical for most PICO questions. PICO questions and outcomes were registered with PROSPERO, an international database of prospectively registered systematic reviews. CONCLUSIONS: We describe formulating and refining research questions and selection of outcomes to guide systematic reviews germane to EMS fatigue risk management. We outline a protocol for applying the Model Process and GRADE framework to create evidence-based guidelines.

Effect of Antihypertensive Medications on the Severity of Obstructive Sleep Apnea: A Systematic Review and Meta-Analysis.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is an independent risk factor for hypertension (HTN). Increasing evidence from animal and human studies suggests that HTN exacerbates OSA. We performed a systematic review and meta-analysis of studies evaluating the effect of anti-hypertensive medications on the severity of OSA. METHODS: A literature search of PubMed and Embase was done using search concepts of OSA, HTN, and drug classes used to treat HTN. Studies that reported changes in the severity of OSA objectively by using apnea-hypopnea index (AHI) or respiratory disturbance index (RDI) were included. Pooled mean difference estimates were calculated. Tests for heterogeneity, publication bias, and subgroup sensitivity analysis were conducted. RESULTS: Of 27,376 studies screened, only 11 met inclusion criteria, including 5 randomized controlled trials and 6 single-arm prospective trials. The pooled mean difference estimate (95% confidence interval [CI]), based on a random-effects model, was -5.69 (95% CI -10.74 to -0.65), consistent with an overall decrease in AHI or RDI attributable to antihypertensive medications. The effect size was even more pronounced, -14.52 (95% CI -25.65 to -3.39), when only studies using diuretics were analyzed. There was no significant heterogeneity or publication bias among the studies. Meta-regression indicated neither age, baseline AHI, nor change in systolic/diastolic blood pressure influenced the results. CONCLUSIONS: Collectively, findings from these relatively small, short-term studies tend to support the contention that treatment with antihypertensive agents confers a statistically significant, albeit small, reduction in the severity of OSA, which may be more pronounced with the use of diuretics.

Well water quality in rural Nicaragua using a low-cost bacterial test and microbial source tracking.

Water-related diseases, particularly diarrhea, are major contributors to morbidity and mortality in developing countries. Monitoring water quality on a global scale is crucial to making progress in terms of population health. Traditional analytical methods are difficult to use in many regions of the world in low-resource settings that face severe water quality issues due to the inaccessibility of laboratories. This study aimed to evaluate a new low-cost method (the compartment bag test (CBT)) in rural Nicaragua. The CBT was used to quantify the presence of Escherichia coli in drinking water wells and aimed to determine the source(s) of any microbial contamination. Results indicate that the CBT is a viable method for use in remote rural regions. The overall quality of well water in Pueblo Nuevo, Nicaragua was deemed unsafe, and results led to the conclusion that animal fecal wastes may be one of the leading causes of well contamination. Elevation and depth of wells were not found to impact overall water quality. However rope-pump wells had a 64.1% reduction in contamination when compared with simple wells.

Systematic Review and Meta-Analysis of Inhaled Toxicants from Waterpipe and Cigarette Smoking.

OBJECTIVE: Waterpipe tobacco smoking (WTS) is an emerging trend worldwide. To inform public health policy and educational programming, we systematically reviewed the biomedical literature to compute the inhaled smoke volume, nicotine, tar, and carbon monoxide (CO) associated with a single WTS session and a single cigarette. METHODS: We searched seven biomedical bibliographic databases for controlled laboratory or natural environment studies designed to mimic human tobacco consumption. Included studies quantified the mainstream smoke of a single cigarette and/or single WTS session for smoke volume, nicotine, tar, and/or CO. We conducted meta-analyses to calculate summary estimates for the inhalation of each unique substance for each mode of tobacco consumption. We assessed between-study heterogeneity using chi-squared and I-squared statistics. RESULTS: Sufficient data from 17 studies were available to derive pooled estimates for inhalation of each exposure via each smoking method. Two researchers working independently abstracted measurement of smoke volume in liters, and nicotine, tar, and CO in milligrams. All numbers included in meta-analyses matched precisely between the two researchers (100% agreement, Cohen's k=1.00). Whereas one WTS session was associated with 74.1 liters of smoke inhalation (95% confidence interval [CI] 38.2, 110.0), one cigarette was associated with 0.6 liters of smoke (95% CI 0.5, 0.7). One WTS session was also associated with higher levels of nicotine, tar, and CO. CONCLUSIONS: One WTS session consistently exposed users to larger smoke volumes and higher levels of tobacco toxicants compared with one cigarette. These computed estimates may be valuable to emphasize in prevention programming.

Patient fears of tumor cell dissemination secondary to surgical interventions-part II.

Patient fears are an ever-present factor of patient care, and addressing those fears is a responsibility of the healthcare provider. One such fear may be of tumor cell dissemination secondary to surgical interventions. Preparing for such discussions will allow the healthcare provider to speak with authority on the topic of tumor dissemination secondary to breast biopsy or surgery, even in a situation where a patient has underlying fears.