Medical device regulation in vascular ageing assessment: a VascAgeNet survey exploring knowledge and perception.

BACKGROUND: Regulation has a key role for medical devices throughout their lifecycle aiming to guarantee effectiveness and safety for users. Requirements of Regulation (EU) 2017/745 (MDR) have an impact on novel and previously approved systems. Identification of key stakeholders' needs can support effective implementation of MDR improving the translation to clinical practice of vascular ageing assessment. The aim of this work is to explore knowledge and perception of medical device regulatory framework in vascular ageing field. RESEARCH DESIGN AND METHODS: A survey was developed within VascAgeNet and distributed in the community by means of the EUSurvey platform. RESULTS: Results were derived from 94 participants (27% clinicians, 62% researchers, 11% companies) and evidenced mostly a fair knowledge of MDR (despite self-judged as poor by 51%). Safety (83%), validation (56%), risk management (50%) were considered relevant and associated with the regulatory process. Structured support and regulatory procedures connected with medical devices in daily practice at the institutional level are lacking (only 33% report availability of a regulatory department). CONCLUSIONS: Regulation was recognized relevant by the VascAgeNet community and specific support and training in medical device regulatory science was considered important. A direct link with the regulatory sector is not yet easily available.

2024 Recommendations for Validation of Noninvasive Arterial Pulse Wave Velocity Measurement Devices.

BACKGROUND: Arterial stiffness, as measured by arterial pulse wave velocity (PWV), is an established biomarker for cardiovascular risk and target-organ damage in individuals with hypertension. With the emergence of new devices for assessing PWV, it has become evident that some of these devices yield results that display significant discrepancies compared with previous devices. This discrepancy underscores the importance of comprehensive validation procedures and the need for international recommendations. METHODS: A stepwise approach utilizing the modified Delphi technique, with the involvement of key scientific societies dedicated to arterial stiffness research worldwide, was adopted to formulate, through a multidisciplinary vision, a shared approach to the validation of noninvasive arterial PWV measurement devices. RESULTS: A set of recommendations has been developed, which aim to provide guidance to clinicians, researchers, and device manufacturers regarding the validation of new PWV measurement devices. The intention behind these recommendations is to ensure that the validation process can be conducted in a rigorous and consistent manner and to promote standardization and harmonization among PWV devices, thereby facilitating their widespread adoption in clinical practice. CONCLUSIONS: It is hoped that these recommendations will encourage both users and developers of PWV measurement devices to critically evaluate and validate their technologies, ultimately leading to improved consistency and comparability of results. This, in turn, will enhance the clinical utility of PWV as a valuable tool for assessing arterial stiffness and informing cardiovascular risk stratification and management in individuals with hypertension.

Is the prolongation latency of visual evoked potentials a pathological sign in children with Down's syndrome without ocular abnormalities? Case-control study of children with Down's syndrome.

OBJECTIVE: To evaluate retino-cortical function in children with Down's syndrome (DS) and no evident ocular abnormalities beyond mild refractive error, by recording visual evoked potentials (VEP) in response to pattern-reversal stimuli and comparing to those of age-matched healthy controls. METHODS AND ANALYSIS: All the children with DS registered at Split-Dalmatia County who met inclusion criteria of no ocular abnormalities and with refraction error between -0.5 and +2.0 D, and their age-matched healthy controls were included in the study (n=36 children, N=72 eyes, for both groups, respectively, with the same age of 9±2 years). Transient VEP was recorded and the waves with a positive peak as a response to a pattern-reversal stimulus, were analysed. The peak P100 latency, defined as the time from the stimulus onset to the main positive peak, and peak to peak amplitudes were measured. RESULTS: While P100 wave amplitudes were comparable between two groups (p=0.804), P100 latencies were from 4.3 to 28.5 ms longer in children with DS (p<0.001). Interocular latency difference between a VEP dominant and an inferior eye was pronounced in healthy (1.2 ms (0.2-4.0), but was almost diminished in children with DS (0.3 ms (0.1-0.5), p<0.001). CONCLUSION: Our study has demonstrated that VEP response is divergent in children with DS compared with their age-matched healthy controls, indicating possible structural or functional abnormalities of the visual cortex. As VEP results are helpful in the diagnosis and treatment planning of vision-related disorders, we should reconsider the use of common VEP diagnostic criteria in subpopulation of children with DS.

Diagnostic Utility of Serum Leucine-Rich α-2-Glycoprotein 1 for Acute Appendicitis in Children.

PURPOSE: The aim of this study is to assess the diagnostic utility of serum leucine-rich α-2-glycoprotein 1 (LRG1) in pediatric patients with acute abdominal pain, admitted to the emergency surgical unit, in order to make a prompt and accurate diagnosis of acute appendicitis. PATIENTS AND METHODS: Pediatric patients older than 5 years of age who presented to the emergency department from 15 October 2021 to 30 June 2022 with acute abdominal pain and suspected acute appendicitis were prospectively recruited in the study. Demographic and clinical data, as well as operative and postoperative data, were recorded. A total of 92 patients were equally distributed into two groups: children with acute appendicitis who underwent laparoscopic appendectomy and non-appendicitis patients, presenting with non-specific abdominal pain. LRG1 levels were determined using a commercially available LRG1 enzyme-linked immunosorbent assay (ELISA) kit. Serum LRG1 levels, as well as other inflammatory markers (white blood cell count (WBC), C-reactive protein (CRP) and absolute neutrophil count) were compared between groups. RESULTS: The median level of LRG1 in serum was significantly higher in the group of children with pathohistologically confirmed acute appendicitis than in the control group, at 350.3 µg/mL (interquartile range (IQR) 165.2-560.3) and 25.7 µg/mL (IQR 14.7-36.8) (p < 0.001), respectively. Receiver operating characteristic area under the curve for LRG1 from serum was 1.0 (95% CI 0.96-1.00; p < 0.001) and the value of >69.1 µg/mL was found to perfectly separate acute appendicitis cases from controls. Additionally, as expected, each of the examined laboratory inflammatory markers provided a significantly higher values in the acute appendicitis group compared to the control group: WBC 14.6 × 109/L (IQR 12.7, 18.7) vs. 7.0 × 109/L (IQR 5.4, 9.0) (p < 0.001), CRP 16.3 mg/dL (IQR 6.9, 50.4) vs. 2.2 mg/dL (IQR 2, 2) (p < 0.001) and absolute neutrophil count 84.6% (IQR 79.5, 89.0) vs. 59.5% (IQR 51.5, 68.6) (p < 0.001). CONCLUSIONS: LRG1 in the serum was found to be a promising novel biomarker, with excellent differentiation of acute appendicitis from non-appendicitis cases in children presenting with non-specific abdominal pain.

Diagnostic Accuracy of Leucine-Rich α-2-Glycoprotein 1 as a Non-Invasive Salivary Biomarker in Pediatric Appendicitis.

The aim of this study is to evaluate the diagnostic accuracy of leucine-rich α-2-glycoprotein 1 (LRG1) in saliva as a novel biomarker for acute appendicitis in the pediatric population. From October 2021 to June 2022, 92 children aged 5 to 17 years who presented with acute abdomen and suspected acute appendicitis were enrolled in this prospective study. The parameters documented included demographic and clinical information, as well as operative and postoperative data. Patients were divided into two groups: those with acute appendicitis who underwent laparoscopic appendectomy (n = 46) and those without appendicitis (n = 46). The total white blood cell (WBC) count, percent of neutrophils, C-reactive protein (CRP) level, and salivary LRG1 were compared between groups. A commercially available enzyme-linked immunosorbent assay (ELISA) LRG kit was used to measure the LRG levels. The median salivary LRG1 level was significantly higher in the group of children with pathohistologically confirmed acute appendicitis compared to the control group: 233.45 ng/mL (IQR 114.9, 531.2) vs. 55.95 ng/mL (IQR 51.5, 117.9), p < 0.001. LRG1 had an overall good receiver-operator characteristic area under the curve of 0.85 (95% CI 0.76-0.92; p < 0.001). The optimal LRG1 cutoff with best separation between acute appendicitis and the controls was >352.6 ng/mL (95% CI from >270.7 to >352.6). Although the specificity was 100% at this cutoff, the sensitivity for identifying appendicitis was 36%. In addition, a significant difference was found between groups in the laboratory values of all inflammatory markers tested: WBC, absolute neutrophil count, and CRP (p < 0.001 for all). Although LRG1 in saliva showed a good AUC parameter and significantly higher values in patients with acute appendicitis compared to the controls, its usefulness in the patient population who present at emergency departments with abdominal pain is debatable. Future studies should focus on investigating its diagnostic potential.

Long-Term Adverse Effects of Mild COVID-19 Disease on Arterial Stiffness, and Systemic and Central Hemodynamics: A Pre-Post Study.

COVID-19-associated vascular disease complications are primarily associated with endothelial dysfunction; however, the consequences of disease on vascular structure and function, particularly in the long term (>7 weeks post-infection), remain unexplored. Individual pre- and post-infection changes in arterial stiffness as well as central and systemic hemodynamic parameters were measured in patients diagnosed with mild COVID-19. As part of in-laboratory observational studies, baseline measurements were taken up to two years before, whereas the post-infection measurements were made 2-3 months after the onset of COVID-19. We used the same measurement protocol throughout the study as well as linear and mixed-effects regression models to analyze the data. Patients (N = 32) were predominantly healthy and young (mean age ± SD: 36.6 ± 12.6). We found that various parameters of arterial stiffness and central hemodynamics-cfPWV, AIx@HR75, and cDBP as well as DBP and MAP-responded to a mild COVID-19 disease. The magnitude of these responses was dependent on the time since the onset of COVID-19 as well as age (pregression_models ≤ 0.013). In fact, mixed-effects models predicted a clinically significant progression of vascular impairment within the period of 2-3 months following infection (change in cfPWV by +1.4 m/s, +15% in AIx@HR75, approximately +8 mmHg in DBP, cDBP, and MAP). The results point toward the existence of a widespread and long-lasting pathological process in the vasculature following mild COVID-19 disease, with heterogeneous individual responses, some of which may be triggered by an autoimmune response to COVID-19.

What Is the Smallest Change in Pulse Wave Velocity Measurements That Can Be Attributed to Clinical Changes in Arterial Stiffness with Certainty: A Randomized Cross-Over Study.

Pulse wave velocity (PWV), a direct measure of arterial stiffness, is a promising biomarker of cardiovascular risk and a cardiovascular surrogate outcome. The resolution for detecting its smallest clinically significant change is dependent on the expected reproducibility, but there is currently no consensus on this. We estimated the PWV reproducibility in a range of intra-subject values that were observed over a 2 week period in a broad range of participants and under clinically relevant experimental conditions (two observers, morning/afternoon sessions, and number of visits) using SphygmoCor and Arteriograph devices. Each participant was recorded 12 times with each device over three visits, one week apart, and two morning and two afternoon recordings were taken per visit. The factors affecting reproducibility and the discrepancies between the consecutive PWV measurements for each device were also examined using multilevel mixed-effect models. We show that current PWV estimation guidance recommending 2 + 1 measurements is suboptimal because the PWV range was outside of the 1 m/s threshold for most of the participants, which is proposed as a minimal clinically important difference. The best reproducibility was yielded with median of four measurements and a 1.1 m/s threshold. Although PWV reproducibility and repeatability are frequently used interchangeably in studies, we demonstrated that despite their relative measures of variability (e.g., coefficient of variation) being comparable, their ranges revealed a clinically significant difference between them. We also found that different physiological variables were predictors of the discrepancy between the consecutive measurements made by the two devices, which is likely due to their distinct modes of operation. The evidence base for PWV reproducibility is limited, and more research is needed to deepen our understanding of the variation in arterial stiffness over time, as well as fluctuations within a population group and in an intervention setting.

Acute myocardial infarction triggered by physical exertion: a systematic review and meta-analysis.

AIMS: While regular physical activity has clear benefits to cardiovascular health, physical exertion can trigger acute myocardial infarction (AMI). We aimed to estimate how many AMIs may be attributed to bouts of physical exertion and to explore possible modifiers of this association. METHODS AND RESULTS: MEDLINE, ISI Web of Science, and Scopus databases were searched for case-crossover studies reporting the relative risk (RR) of exertion-related AMI and exposure prevalence in the control periods. We used the random-effects model to pool the RR estimates and the mixed-effects model and random-effects meta-regression for subgroup analyses and estimated the population attributable fraction (PAF) at the population level and in different subgroups. The study met the Preferred Reporting Items for Systematic Reviews and Meta-Analyses requirements. Twelve studies including 19 891 AMI patients met the criteria for inclusion. There was a strong overall association between episodic physical exertion and AMI [RR = 3.46; 95% confidence interval (CI), 3.16-3.78]. The total PAF was 10.6% (95% CI, 9.44-11.83). For each additional year of age, the RR of exertion-related AMI increased by ∼3%, but the PAF decreased by 2%. For each additional time of habitual activity per week, the RR of exertion-related AMI decreased by ∼43%. The impact was greater among those engaged in physical exertion one to three times a week (≥20% of cases) and among those who did not take compared with those who took ß-blockers (P = 0.049). CONCLUSION: Every tenth AMI may be assigned to physical exertion. The impact was more pronounced among younger patients, those exposed to exertion one to three times a week, and those not taking ß-blockers.

Twelve case-crossover studies with 19 891 patients were included in our systematic review with meta-analysis to estimate how many acute myocardial infarctions may be attributed to bouts of physical exertion and to explore possible modifiers of this association.Approximately 10.6% of all acute myocardial infarctions may be attributed to physical exertion, but the impact was greater in younger individuals or those engaged in exertion one to three times/week. Among the latter, exertion triggers approximately every fifth infarction.Beta-blockers may provide a protection from the triggering effect of physical exertion.

Factors Associated with the Quality and Transparency of National Guidelines: A Mixed-Methods Study.

We assessed the methodological quality and transparency of all the national clinical practice guidelines that were published in Croatia up until 2017 and explored the factors associated with their quality rating. An in-depth quantitative and qualitative analysis was performed using rigorous methodology. We evaluated the guidelines using a validated AGREE II instrument with four raters; we used multiple linear regressions to identify the predictors of quality; and two focus groups, including guideline developers, to further explore the guideline development process. The majority of the guidelines (N = 74) were developed by medical societies. The guidelines' quality was rated low: the median standardized AGREE II score was low, 36% (IQR 28-42), and so were the overall-assessments. The aspects of the guidelines that were rated best were the "clarity of presentation" and the "scope and purpose" (median ≥ 59%); however, the other four domains received very low scores (15-33%). Overall, the guideline quality did not improve over time. The guidelines that were developed by medical societies scored significantly worse than those developed by governmental, or unofficial working groups (12-43% per domain). In focus group discussions, inadequate methodology, a lack of implementation systems in place, a lack of awareness about editorial independence, and broader expertise/perspectives in working groups were identified as factors behind the low scores. The factors identified as affecting the quality of the national guidelines may help stakeholders who are developing interventions and education programs aimed at improving guideline quality worldwide.

Synthesizing quantitative and qualitative information on multiple comparisons of health interventions to facilitate knowledge transfer: an example from an EUnetHTA multi-HTA.

OBJECTIVE: Presenting an approach to synthesize quantitative and qualitative information from systematic reviews of multiple health interventions. METHODS: Within the context of an EUnetHTA multi-health technology assessment of twenty-three surgical techniques, we developed synthetic single tables, using color gradients and abbreviations, with information on which technologies had been compared, estimates of the size of differences for available comparisons, their clinical relevance, and certainty of the related evidence. RESULTS: The proposed methodology provided, through a single depiction, information normally included in multiple figures/tables such as network plots, league tables, and summary of findings tables. CONCLUSION: Transferring information on benefits, risks, and certainty of the available evidence on health interventions may be challenging, especially when assessing multiple treatments: more pieces of information need to be integrated in order to show an overall picture for each of the chosen outcomes, and usual reporting tools may be targeted to researchers more than to different kinds of decision makers. While more in-depth layers of information can always be added to satisfy needs of different audiences, the proposed tools could favor a quick interpretation of articulated scientific data by both decision makers and researchers.

The effects of experimental, meteorological, and physiological factors on short-term repeated pulse wave velocity measurements, and measurement difficulties: A randomized crossover study with two devices.

Background: Large longitudinal studies with repeated pulse wave velocity (PWV) measurements, a direct measure of arterial stiffness, are required to realize the full potential of arterial stiffness in clinical practice. To facilitate such studies it is important to increase the power of a study by reducing within-subject variability of PWV, and to ease the use of a PWV device in clinical settings by minimizing PWV measurement difficulties. Methods: We systematically investigated experimental setting and meteorological conditions, as well as physiological factors and participant characteristics, to determine whether and to what extent they affected: between- and within-subjects variability of PWV recordings, and measurement difficulties of a particular device. We conducted a 2-week longitudinal block-randomized cross-over study with two blinded observers and two commonly used devices: applanation tonometry SphygmoCor CvMS and oscillometric Arteriograph to assess carotid-femoral (cfPWV) or aortic (PWVao) PWV, respectively. Our sample had uniform and wide-spread distribution of age, blood pressures, hypertensive status and BMI. Each participant (N = 35) was recorded 12 times over 3 visiting days, 7 days apart. On each day, recordings were made twice in the morning (7-10 a.m.) and afternoon (16-18 p.m.). Data were analyzed using multilevel mixed-effects models, separately for each device. Results: In addition to age and mean arterial pressure (MAP) that strongly affected both cfPWV and PWVao, other significant factors appeared to indicate a measurement approach. cfPWV as a more direct measure of arterial stiffness was additionally affected by hypertension status, outdoor temperature, interaction of MAP with outdoor temperature and the order of visit, with MAP within-subject variability contributing on average 0.27 m/s to difference in repeated measurements at 5°C and 0.004 m/s at 25°C. PWVao measurements derived at a single brachial site were more dependent on age than cfPWV and also depended on personal characteristics such as height and sex, and heart rate; with within-subject MAP variability adding on average 0.23 m/s to the difference in repeated measures. We also found that female sex significantly increased, and recording in afternoon vs. morning significantly decreased measurement difficulties of both devices. Conclusion: We identified factors affecting PWV recordings and measurement-difficulties and propose how to improve PWV measuring protocols.

The Effect of Subcutaneous and Intraperitoneal Instillation of Local Anesthetics on Postoperative Pain after Laparoscopic Varicocelectomy: A Randomized Controlled Trial.

BACKGROUND: The main goal of the present randomized clinical trial was to investigate the effects of subcutaneous administration of two different local anesthetics at trocar incision sites at the abdominal wall in combination with intraoperative intraperitoneal instillation of local anesthetics, on the character of postoperative pain, in adolescents who underwent laparoscopic varicocelectomy. METHODS: A total of 60 patients with a median age of 16 years, who received laparoscopic varicocele repair, were included in this randomized clinical trial. The patients were randomly assigned to three study groups receiving 2% lidocaine, 0.5% levobupivacaine, or the control group. The Visual Analogue Scale (VAS) was used by a blinded nurse at four different time points (2, 6, 12 and 24 h after the surgery) to measure pain intensity. RESULTS: The significant effect of time on the pain intensity (p = 0.001) was found. Additionally, the interaction between time and different local analgesics (p < 0.001) was observed. In patients in whom 0.5% levobupivacaine has been used, significantly lower VAS pain scores were recorded at each time point assessed, in comparison with the patients who received 2% lidocaine or the patients from the control group in whom no local anesthetic was applied (p < 0.001). Furthermore, in patients in whom 2% lidocaine was administrated, significantly lower pain levels according to VAS were reported than in those from the control group, except for the time point at 24 h after surgery when pain levels were comparable. Concerning the postoperative pain control, the number of patients who requested oral analgesics postoperatively was significantly lower in the group of patients in whom local anesthetic was administrated intraoperatively (2% lidocaine-n = 4, 20%; 0.5% levobupivacaine-n = 1, 5%) compared to the patients who did not receive any local anesthetic during the surgery (n = 13; 65%) (p < 0.001). CONCLUSION: A significant reduction in postoperative pain intensity and analgesics consumption in patients undergoing laparoscopic varicocelectomy who received intraoperative local anesthetic was observed. The best effect on postoperative pain intensity, according to the VAS score, was achieved by 0.5% levobupivacaine.

Systematic review and meta-analyses of studies analysing instructions to authors from 1987 to 2017.

To gain insight into changes of scholarly journals' recommendations, we conducted a systematic review of studies that analysed journals' Instructions to Authors (ItAs). We summarised results of 153 studies, and meta-analysed how often ItAs addressed: 1) authorship, 2) conflicts of interest, 3) data sharing, 4) ethics approval, 5) funding disclosure, and 6) International Committee of Medical Journal Editors' Uniform Requirements for Manuscripts. For each topic we found large between-study heterogeneity. Here, we show six factors that explained most of that heterogeneity: 1) time (addressing of topics generally increased over time), 2) country (large differences found between countries), 3) database indexation (large differences found between databases), 4) impact factor (topics were more often addressed in highest than in lowest impact factor journals), 5) discipline (topics were more often addressed in Health Sciences than in other disciplines), and 6) sub-discipline (topics were more often addressed in general than in sub-disciplinary journals).

Cannabinoids for the treatment of dementia.

BACKGROUND: Dementia is a common chronic condition, mainly affecting older adults, characterised by a progressive decline in cognitive and functional abilities. Medical treatments for dementia are limited. Cannabinoids are being investigated for the treatment of dementia. OBJECTIVES: To determine the efficacy and safety of cannabinoids for the treatment of dementia. SEARCH METHODS: We searched ALOIS - the Cochrane Dementia and Cognitive Improvement Group's Specialised Register - on 8 July 2021, using the terms cannabis or cannabinoid or endocannabinoid or cannabidiol or THC or CBD or dronabinol or delta-9-tetrahydrocannabinol or marijuana or marihuana or hashish. The register contains records from all major healthcare databases (the Cochrane Library, MEDLINE, Embase, PsycINFO, CINAHL, LILACS), as well as from many clinical trials registries and grey literature sources. SELECTION CRITERIA: We included all randomised controlled trials (RCTs) of cannabinoids for the treatment of dementia. We included participants of any age and of either sex with diagnosed dementia of any subtype, or with unspecified dementia of any severity, from any setting. We considered studies of cannabinoids administered by any route, at any dose, for any duration, compared with placebo, no treatment, or any active control intervention. DATA COLLECTION AND ANALYSIS: Two review authors independently screened and selected studies for inclusion, extracted data, and assessed the risk of bias in included studies. When necessary, other review authors were involved in reaching consensus decisions. We conducted meta-analyses using a generic inverse variance fixed-effect model to derive estimates of effect size. We used GRADE methods to assess our confidence in the effect estimates. MAIN RESULTS: We included four studies (126 participants) in this review. Most participants had Alzheimer's disease; a few had vascular dementia or mixed dementia. Three studies had low risk of bias across all domains; one study had unclear risk of bias for the majority of domains.  The included studies tested natural delta-9-tetrahydrocannabinol (THC) (Namisol) and two types of synthetic THC analogue (dronabinol and nabilone). Three trials had a cross-over design. Interventions were applied over 3 to 14 weeks; one study reported adverse events over 70 weeks of follow-up. One trial was undertaken in the USA, one in Canada, and two in The Netherlands. Two studies reported non-commercial funding, and two studies were conducted with the support of both commercial and non-commercial funding. Primary outcomes in this review were changes in global and specific cognitive function, overall behavioural and psychological symptoms of dementia (BPSD), and adverse events. We found very low-certainty evidence suggesting there may be little or no clinically important effect of a synthetic THC analogue on cognition assessed with the standardised Mini-Mental State Examination (sMMSE) (mean difference (MD) 1.1 points, 95% confidence interval (CI) 0.1 to 2.1; 1 cross-over trial, 28 participants).  We found low-certainty evidence suggesting there may be little or no clinically important effect of cannabinoids on overall behavioural and psychological symptoms of dementia assessed with the Neuropsychiatric Inventory (or its modified nursing home version) (MD -1.97, 95% CI -3.87 to -0.07; 1 parallel group and 2 cross-over studies, 110 participants). All included studies reported data on adverse events. However, the total number of adverse events, the total numbers of mild and moderate adverse events, and the total number of serious adverse events (SAEs) were not reported in a way that permitted meta-analysis.  There were no clear differences between groups in numbers of adverse events, with the exception of sedation (including lethargy), which was more frequent among participants taking nabilone (N = 17) than placebo (N = 6) (odds ratio (OR) 2.83, 95% CI 1.07 to 7.48; 1 cross-over study, 38 participants). We judged the certainty of evidence for adverse event outcomes to be low or very low due to serious concerns regarding imprecision and indirectness. AUTHORS' CONCLUSIONS: Based on data from four small, short, and heterogeneous placebo-controlled trials, we cannot be certain whether cannabinoids have any beneficial or harmful effects on dementia. If there are benefits of cannabinoids for people with dementia, the effects may be too small to be clinically meaningful. Adequately powered, methodologically robust trials with longer follow-up are needed to properly assess the effects of cannabinoids in dementia.

The global incidence of in-flight medical emergencies: A systematic review and meta-analysis of approximately 1.5 billion airline passengers.

BACKGROUND: Medical emergencies during short- or long-haul commercial airline flights have become more commonplace due to the aviation industry's contemporary growth, the popularization of commercial flights, and an increased aging of air travelers with significant comorbidities. However, the precise incidence of onboard medical events on commercial airlines and the most common medical conditions is unclear. METHODS: In this systematic review and meta-analysis, we explored the incidence of in-flight medical emergencies among airline passengers and estimated the incidence rate by physiological body system, or organ class/syndrome for emergencies that may be associated with different body systems. We limited our search to cohort studies published between 1945 to October 31, 2020 in MEDLINE, Embase, Cochrane Library and official reports from the Federal Aviation Administration/International Air Transport Association, regardless of the language of publication. Only studies that evaluated the overall frequency of onboard medical events on commercial air carriers (in which they also presented the total number of annual revenue passengers) and the frequency of events by physiological body systems or organ class/syndrome were included. We excluded case reports and case series, systematic or narrative reviews, and studies addressing specific health-related conditions. Two independent investigators performed first- and second-phase study screening, abstracted data, and appraised risk of bias. We rated the certainty of evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Using a quality effect model, we meta-analyzed data associated with the incidence of in-flight medical emergencies, all-cause fatality, incidence of medical events by medical condition category, frequency of en-route diversion, presence of medical personnel on board, and the use of an automatic external defibrillator. We also extracted data regarding the cost of flight diversion. RESULTS: Of 18 individual studies with approximately 1.5 billion passengers, 11 reported the overall incidence of in-flight medical emergencies. Low certainty of evidence suggested that the global incidence of in-flight medical emergencies was 18.2 events per million passengers (95% CI 0.5 to 53.4 per million; I2 = 100%, P < 0.001, very low certainty), and an all-cause mortality rate was 0.21 per million passengers (95% CI 0 to 0.76 per million; I2 = 99%, P < 0.001, low certainty). The four most common categories of medical conditions or syndromes during flight were syncope, gastrointestinal events, respiratory and neurological diagnostic groups. The diversion rate was 11.1 per 100,000 flights (95% CI 5.9 to17.6 per 100,000 flights; I2 = 97%, P < 0.001), with an average cost ranging from $15,000 to $893,000 per unplanned emergency landing across studies which examined this outcome. CONCLUSIONS: In-flight medical events on commercial travels are extremely low with a corresponding very low in-flight mortality rate. Associated costs derived from en-route diversion might significantly influence airlines' budgetary equilibrium. Novel and modern standardized reporting systems or platforms should be internationally provided and enforced by health and aviation authorities to obtain higher quality patient-passengers datasets. Onboard volunteer medical providers must be aware of everyday life-threatening events during commercial flights and should consider the establishment of a connection between the aircraft and ground-based medical advisory services while assisting in-flight medical events.

Comparison of new versus reused Harmonic scalpel performance in laparoscopic appendectomy in patients with acute appendicitis-a randomized clinical trial.

BACKGROUND: The aim of this study was to compare lateral thermal damage of the appendix and clinical outcomes after laparoscopic appendectomy using new versus reused Harmonic scalpels. METHODS: A total of 100 consecutive patients with acute appendicitis who underwent laparoscopic appendectomy were enrolled in the two-center, randomized clinical trial. Using a computer random number generator, patients were allocated to new or reused group. Histopathological measurement of lateral thermal damage of the appendiceal base and mesoappendix, speed of transection of the appendiceal base, duration of surgery, subjective rating of device functionality, length of hospital stay, and complications were compared within groups. RESULTS: The median lateral thermal damage on the appendiceal base in the new group (N = 49) was 0.2 mm (IQR 0.1-0.2) and 0.1 mm (IQR 0.1-0.3) in the reused group (N = 51) (P = 0.644), while on the mesoappendix for both groups, thermal damage was 0.1 mm (IQR 0.1-0.2) (P = 0.418). The median time required for base transection in both groups was 8 s (IQR 7-9) (P = 0.776). The median duration of surgery was also comparable between the groups (22 min, IQR 20-30 vs 25 min, IQR 21-35; P = 0.233). Two postoperative complications in the new group and one in the reused group were recorded (4% vs 2%; P = 0.536). Surgeons' subjective assessment of the instrument did not reveal significant difference between the groups in all of the investigated categories. CONCLUSIONS: The results of our study support the reuse of Harmonic scalpels especially in the settings where economic constraints might hamper access to minimally invasive surgery to a larger number of patients. The results obtained on laparoscopic appendectomy might not be reproducible to other more demanding surgical procedures. TRIAL REGISTRATION: ClinicalTrials.gov registry under identifier NCT04226482.

Clinical, laboratory and radiological characteristics and outcomes of novel coronavirus (SARS-CoV-2) infection in humans: A systematic review and series of meta-analyses.

New evidence on the COVID-19 pandemic is being published daily. Ongoing high-quality assessment of this literature is therefore needed to enable clinical practice to be evidence-based. This review builds on a previous scoping review and aimed to identify associations between disease severity and various clinical, laboratory and radiological characteristics. We searched MEDLINE, CENTRAL, EMBASE, Scopus and LILACS for studies published between January 1, 2019 and March 22, 2020. Clinical studies including ≥10 patients with confirmed COVID-19 of any study design were eligible. Two investigators independently extracted data and assessed risk of bias. A quality effects model was used for the meta-analyses. Subgroup analysis and meta-regression identified sources of heterogeneity. For hospitalized patients, studies were ordered by overall disease severity of each population and this order was used as the modifier variable in meta-regression. Overall, 86 studies (n = 91,621) contributed data to the meta-analyses. Severe disease was strongly associated with fever, cough, dyspnea, pneumonia, any computed tomography findings, any ground glass opacity, lymphocytopenia, elevated C-reactive protein, elevated alanine aminotransferase, elevated aspartate aminotransferase, older age and male sex. These variables typically increased in prevalence by 30-73% from mild/early disease through to moderate/severe disease. Among hospitalized patients, 30-78% of heterogeneity was explained by severity of disease. Elevated white blood cell count was strongly associated with more severe disease among moderate/severe hospitalized patients. Elevated lymphocytes, low platelets, interleukin-6, erythrocyte sedimentation rate and D-dimers showed potential associations, while fatigue, gastrointestinal symptoms, consolidation and septal thickening showed non-linear association patterns. Headache and sore throat were associated with the presence of disease, but not with more severe disease. In COVID-19, more severe disease is strongly associated with several clinical, laboratory and radiological characteristics. Symptoms and other variables in early/mild disease appear non-specific and highly heterogeneous. Clinical Trial Registration: PROSPERO CRD42020170623.

Vitamin B12 Supplementation in Addition to Folic Acid and Iron Improves Hematological and Biochemical Markers in Pregnancy: A Randomized Controlled Trial.

Vitamin B12 plays an important role in cell division and is of vital importance during pregnancy. Iron and B12 deficiency increase the risk of neonatal morbidity and the outcome of the overall pregnancy. The aim of our study was to analyze whether the use of vitamin B12, with standard supplements of folic acid and iron among nonanemic pregnant women, will result in improvements of hemogram parameters in terms of hematological and biochemical markers. Study participants were 200 healthy pregnant women, randomized into an intervention group and a control group, recruited from gynecological primary care practices in Split, Croatia. In addition to standard supplementation (350 mg/day ferrous iron, 5 mg folic acid), participants in the intervention group were given 5 µg of vitamin B12 each morning for 100 days. Both biochemical and hematological measurings were conducted in two intervals: 8th-10th week of gestation and then again in the 34th-36th week of gestation. Participants in the control group were given only standard-of-care iron and folic acid supplementation. Significantly lower values of haptoglobin postintervention, compared with baseline, were found only in the intervention group; for erythrocytes, significantly lower values postintervention were found only in the control group. For parameter hematocrit, we found decreased values postintervention, compared with baseline, in both intervention and control group; however, this decrease was within the reference range for the control group, whereas it was above the reference range for the intervention group. The results of this study indicated that intervention with vitamin B12 in pregnancy reduces possibilities of the onset of anemia, but within reference range.