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Estimates of the incidence of the acute respiratory distress syndrome (ARDS) in high- and middle-income countries vary from 10.1 to 86.2 per 100,000 person-years in the general population. The epidemiology of ARDS has not been reported for a low-income country at the level of the population, hospital, or intensive care unit (ICU). The Berlin definition may not allow identification of ARDS in resource-constrained settings. To estimate the incidence and outcomes of ARDS at a Rwandan referral hospital using the Kigali modification of the Berlin definition: without requirement for positive end-expiratory pressure, hypoxia cutoff of SpO2/FiO2 less than or equal to 315, and bilateral opacities on lung ultrasound or chest radiograph. We screened every adult patient for hypoxia at a public referral hospital in Rwanda for 6 weeks. For every patient with hypoxia, we collected data on demographics and ARDS risk factors, performed lung ultrasonography, and evaluated chest radiography when available. Forty-two (4.0%) of 1,046 hospital admissions met criteria for ARDS. Using various prespecified cutoffs for the SpO2/FiO2 ratio resulted in almost identical hospital incidence values. Median age for patients with ARDS was 37 years, and infection was the most common risk factor (44.1%). Only 30.9% of patients with ARDS were admitted to an ICU, and hospital mortality was 50.0%. Using traditional Berlin criteria, no patients would have met criteria for ARDS. ARDS seems to be a common and fatal syndrome in a hospital in Rwanda, with few patients admitted to an ICU. The Berlin definition is likely to underestimate the impact of ARDS in low-income countries, where resources to meet the definition requirements are lacking. Although the Kigali modification requires validation before widespread use, we hope this study stimulates further work in refining an ARDS definition that can be consistently used in all settings.

There has been a dramatic increase in the number of children diagnosed with autism spectrum disorders (ASD) worldwide. Recently anecdotal evidence of possible therapeutic effects of cannabis products has emerged. The aim of this study is to characterize the epidemiology of ASD patients receiving medical cannabis treatment and to describe its safety and efficacy. We analysed the data prospectively collected as part of the treatment program of 188 ASD patients treated with medical cannabis between 2015 and 2017. The treatment in majority of the patients was based on cannabis oil containing 30% CBD and 1.5% THC. Symptoms inventory, patient global assessment and side effects at 6 months were primary outcomes of interest and were assessed by structured questionnaires. After six months of treatment 82.4% of patients (155) were in active treatment and 60.0% (93) have been assessed; 28 patients (30.1%) reported a significant improvement, 50 (53.7%) moderate, 6 (6.4%) slight and 8 (8.6%) had no change in their condition. Twenty-three patients (25.2%) experienced at least one side effect; the most common was restlessness (6.6%). Cannabis in ASD patients appears to be well tolerated, safe and effective option to relieve symptoms associated with ASD.

The purpose of this study was to assess the predictive value of prostate specific antigen density (PSAD) for detection of clinically significant prostate cancer in men undergoing systematic transrectal ultrasound (TRUS)-guided prostate biopsy. We retrospectively analyzed data of men who underwent TRUS-guided prostate biopsy because of elevated PSA (≤ 20 ng/ml) or abnormal digital rectal examination. Receiver operating characteristic curve analysis to compare PSA and PSAD performance and chi-square automatic interaction detector methodologies were used to identify predictors of clinically significant cancer (Gleason score ≥ 7 or international society of urological pathology grade group ≥ 2). Nine-hundred and ninety-two consecutive men with a median age of 66 years (IQR 61–71) were included in the study. Median PSAD was 0.10 ng/ml 2 (IQR 0.10–0.22). Prostate adenocarcinoma was diagnosed in 338 men (34%). Clinically significant prostate adenocarcinoma was diagnosed in 167 patients (50% of all cancers and 17% of the whole cohort). The AUC to predict clinically significant prostate cancer was 0.64 for PSA and 0.78 for PSAD (P < 0.001). The highest Youden's index for PSAD was at 0.20 ng/ml 2 with 70% sensitivity and 79% specificity for the diagnosis of clinically significant cancer. Men with PSAD < 0.09 ng/ml 2 had only 4% chance of having clinically significant disease. The detection rate of clinically significant prostate cancer in patients with PSAD between 0.09 and 0.19 ng/ml 2 was significantly higher when prostate volume was less than 33 ml. In conclusion, PSAD was a better predictor than PSA alone of clinically significant prostate cancer in patients undergoing TRUS-guided biopsy. Patients with PSAD below 0.09 ng/ml 2 were unlikely to harbor clinically significant prostate cancer. Combining PSAD in the gray zone (0.09–0.19) with prostate volume below 33 ml adds diagnostic value of clinically significant prostate cancer.

Background Out-of-hospital-cardiac arrest (OHCA) is frequently linked to environmental exposures. Climate change and global warming phenomenon have been found related to cardiovascular morbidity, however there is no agreement on their impact on OHCA occurrence. In this nationwide analysis, we aimed to assess the incidence of the OHCA events attended by emergency medical services (EMS), in relation to meteorological conditions: temperature, humidity, heat index and solar radiation. Methods We analyzed all adult cases of OHCA in Israel attended by EMS during 2016–2017. In the case-crossover design, we compared ambient exposure within 72 h prior to the OHCA event with exposure prior to the four control times using conditional logistic regression in a lag-distributed non-linear model. Results There were 12,401 OHCA cases (68.3% were pronounced dead-on-scene). The patients were on average 75.5 ± 16.2 years old and 55.8% of them were males. Exposure to 90th and 10th percentile of temperature adjusted to humidity were positively associated with the OHCA with borderline significance (Odds Ratio (OR) =1.20, 95%CI 0.97; 1.49 and OR 1.16, 95%CI 0.95; 1.41, respectively). Relative humidity below the 10th percentile was a risk factor for OHCA, independent of temperature, with borderline significance (OR = 1.16, 95%CI 0.96; 1.38). Analysis stratified by seasons revealed an adverse effect of exposure to 90th percentile of temperature when estimated in summer (OR = 3.34, 95%CI 1.90; 3.5.86) and exposure to temperatures below 10th percentile in winter (OR = 1.75, 95%CI 1.23; 2.49). Low temperatures during a warm season and high temperatures during a cold season had a protective effect on OHCA. The heat index followed a similar pattern, where an adverse effect was demonstrated for extreme levels of exposure. Conclusions Evolving climate conditions characterized by excessive heat and low humidity represent risk factors for OHCA. As these conditions are easily avoided, by air conditioning and behavioral restrictions, necessary prevention measures are warranted.

Lactic dehydrogenase reflects target organ damage, and is associated with mortality in patients with infectious diseases. The purpose of this study was to examine associations of serum lactic dehydrogenase levels with mortality, target organ damage and length of hospital stay in adults with pulmonary and non-pulmonary infections. This nationwide retrospective cohort study comprised patients admitted with infections, to medical and surgical departments in eight tertiary hospitals during 2001-2020. Patients with available serum lactic dehydrogenase levels on admission and one week after were included, and stratified by the source of their infection: pulmonary vs. non-pulmonary. Associations of lactic dehydrogenase levels with mortality and target organ damage were analyzed using multivariable logistic regression models. Quantile regression was used for multivariable analysis of the median length of stay. The study included 103,050 patients (45.4% male, median age: 69 years); 44,491 (43.1%) had pulmonary infections. The median serum lactic dehydrogenase levels on admission were higher in patients with pulmonary than non-pulmonary infections (418 vs. 385 units per liter (U/L), p<0.001). In a multivariable logistic regression model, elevated serum lactic dehydrogenase levels (480-700 U/L, 700-900 U/L and >900 U/L), compared with <480 U/L, were associated with in-hospital mortality (OR = 1.81, 2.85 and 3.69, respectively) and target organ damage (OR = 1.19, 1.51 and 1.80, respectively). The median stay increased with increasing elevated lactic dehydrogenase levels (+0.3, +0.5 and +0.4 days, respectively). Among patients with lactic dehydrogenase levels >900 U/L, mortality, but none of the other examined outcomes, was greater among those with pulmonary than non-pulmonary infections. Among hospitalized patients with infectious diseases, lactic dehydrogenase levels were associated with mortality and target organ damage, and were similar in patients with pulmonary and non-pulmonary infections. Among patients with lactic dehydrogenase levels >900 U/L, mortality was prominently higher among those with pulmonary than non-pulmonary infections.

In recent years, the use and impact of telemedicine for providing health care services to patients has increased, reducing the requirement for physical, in-person encounters. This study aimed to compare the use of telemedicine for outpatient visits versus in-person visits across different medical specialties; assess its association with clinical outcomes; and examine the influence of patient and physician characteristics on telemedicine use in a large, tertiary, teaching hospital. The study cohort consisted of adult patients who attended outpatient clinics in five medical fields (psychiatry, endocrinology, nephrology, hemato-oncology, and gastroenterology) in 2019 and survived until the beginning of 2020. Telemedicine use during the period of 2019-2021 was the main exposure of interest. The primary outcomes were emergency department (ED) referrals and hospitalizations. The analysis used multivariate mixed models and subgroup analysis by patient demographic characteristics, chronic disease medical fields, and physicians' characteristics. The cohort included 32,445 patients. In 2019, a total of 99.6% (82,668/83,000) of visits were in person, and by 2020-2021, a total of 22.6% (10,850/48,120) of patients had used telemedicine. Telemedicine patients were slightly older (standardized mean difference=0.281; P<.001), with a higher comorbidity burden than in-person patients or patients without visits (standardized mean difference=0.328; P<.001). Presurge telemedicine users had higher rates of ED referrals (incidence rate ratio [IRR] 1.15, 95% CI 1.09-1.21) and hospitalizations (IRR 1.14, 95% CI 1.08-1.20) than in-person visit users. These ratios remained stable during the surge (IRR 1.1, 95% CI 1.06-1.16 and IRR 1.12, 95% CI 1.05-1.19, respectively), with no evidence of worsening outcomes for telemedicine users relative to in-person care. Health care providers with higher telemedicine use had reduced rates of ED referrals (IRR 0.85, 95% CI 0.79-0.91) and hospitalizations (IRR 0.78, 95% CI 0.72-0.84) than providers with lower telemedicine use. This study provides insights into telemedicine use patterns and their association with clinical outcomes in chronic disease management. Our findings suggest that the increase in telemedicine use was not associated with a rise in ED referrals or hospitalizations when compared to in-person visits. It highlights the importance of health care providers' perspectives and use of remote visits. Telemedicine should be tailored to individual patient-physician needs, considering the nature of the patient's disease.

Vaccination, especially with multiple doses, provides substantial population-level protection against COVID-19, but emerging variants of concern (VOC) and waning immunity represent significant risks at the individual level. Here we identify correlates of protection (COP) in a multicenter prospective study following 607 healthy individuals who received three doses of the Pfizer-BNT162b2 vaccine approximately six months prior to enrollment. We compared 242 individuals who received a fourth dose to 365 who did not. Within 90 days of enrollment, 239 individuals contracted COVID-19, 45% of the 3-dose group and 30% of the four-dose group. The fourth dose elicited a significant rise in antibody binding and neutralizing titers against multiple VOCs reducing the risk of symptomatic infection by 37% [95%CI, 15%-54%]. However, a group of individuals, characterized by low baseline titers of binding antibodies, remained susceptible to infection despite significantly increased neutralizing antibody titers upon boosting. A combination of reduced IgG levels to RBD mutants and reduced VOC-recognizing IgA antibodies represented the strongest COP in both the 3-dose group (HR = 6.34, p  = 0.008) and four-dose group (HR = 8.14, p  = 0.018). We validated our findings in an independent second cohort. In summary combination IgA and IgG baseline binding antibody levels may identify individuals most at risk from future infections. Vaccination with multiple doses has been proven effective against severe COVID-19, but protection levels widely vary among individuals. This study examines the serological and immunological profiles in recipients of multiple doses of Pfizer BNT162b2 vaccine for immune markers that correlate with protection against and susceptibility for SARS-CoV-2 infection.

Purpose The effect of advanced age per se versus severity of chronic and acute diseases on the short- and long-term survival of older patients admitted to the intensive care unit (ICU) remains unclear. Methods Intensive care unit admissions to the surgical ICU and medical ICU of patients older than 65 years were analyzed. Patients were divided into three age groups: 65–74, 75–84, and 85 and above. The primary endpoints were 28-day and 1-year mortality. Results The analysis focused on 7,265 patients above the age of 65, representing 45.7 % of the total ICU population. From the first to third age group there was increased prevalence of heart failure (25.9–40.3 %), cardiac arrhythmia (24.6–43.5 %), and valvular heart disease (7.5–15.8 %). There was reduced prevalence of diabetes complications (7.5–2.4 %), alcohol abuse (4.1–0.6 %), chronic obstructive pulmonary disease (COPD) (24.4–17.4 %), and liver failure (5.0–1.0 %). Logistic regression analysis adjusted for gender, sequential organ failure assessment, do not resuscitate, and Elixhauser score found that patients from the second and third age group had odds ratios of 1.38 [95 % confidence interval (CI) 1.19–1.59] and 1.53 (95 % CI 1.29–1.81) for 28-day mortality as compared with the first age group. Cox regression analysis for 1-year mortality in all populations and in 28-day survivors showed the same trend. Conclusions The proportion of elderly patients from the total ICU population is high. With advancing age, the proportion of various preexisting comorbidities and the primary reason for ICU admission change. Advanced age should be regarded as a significant independent risk factor for mortality, especially for ICU patients older than 75.

The association between glucose intolerance, elevated blood pressure and abnormal lipid levels is well established and comprises the basis of metabolic syndrome pathophysiology. We hypothesize that abnormal preconception lipid levels are associated with the increased risk of severe pregnancy complications such as preeclampsia and gestational diabetes mellitus. We included all singleton deliveries (n = 27,721) of women without known cardiovascular morbidity and preeclampsia and gestational diabetes mellitus during previous pregnancies. Association between preconception low high density lipoprotein cholesterol (HDLc level≤50 mg/dL), high triglycerides (level≥150 mg/dL) and the primary outcome (composite of gestational diabetes mellitus/or preeclampsia) was assessed using Generalized Estimation Equations. Primary outcome of preeclampsia and/or gestational diabetes was observed in a total of 3,243 subjects (11.7%). Elevated triglycerides and low HDLc were independently associated with the primary outcome: with odds ratio (OR) of 1.61 (95% CI 1.29-2.01) and OR = 1.33 (95% CI 1.09-1.63), respectively, after adjusting for maternal age, weight, blood pressure, repeated abortions, fertility treatments and fasting glucose. There was an interaction between the effects of HDLc≤50 mg/dL and triglycerides≥150 mg/dL with an OR of 2.69 (95% CI 1.73-4.19). Our analysis showed an increased rate of preeclampsia and/or gestational diabetes in women with low HDLc and high triglycerides values prior to conception. In view of the severity of these pregnancy complications, we believe this finding warrants a routine screening for the abnormal lipid profile among women of a child-bearing age.

This population-based study aimed to investigate the prognostic value of ambulatory serum chloride abnormalities, often ignored by physicians. The study population included all non-hospitalized adult patients, insured by \"Clalit\" Health Services in Israel's southern district, who underwent at least 3 serum chloride tests in community-based clinics during 2005-2016. For each patient, each period with low (≤97 mmol/l), high (≥107 mmol/l) or normal chloride levels were recorded. A Cox proportional hazards model was used to estimate the mortality risk of hypochloremia and hyperchloremia periods. 664,253 serum chloride tests from 105,655 subjects were analyzed. During a median follow up of 10.8 years, 11,694 patients died. Hypochloremia (≤ 97 mmol/l) was independently associated with elevated all-cause mortality risk after adjusting for age, co-morbidities, hyponatremia and eGFR (HR 2.41, 95%CI 2.16-2.69, p<0.001). Crude hyperchloremia (≥107 mmol/L) was not associated with all-cause mortality (HR 1.03, 95%CI 0.98-1.09 p = 0.231); as opposed to hyperchloremia ≥108 mmol/l (HR 1.14, 95%CI 1.06-1.21 p<0.001). Secondary analysis revealed a dose-dependent elevated mortality risk for chloride levels of 105 mmol/l and below, well within the \"normal\" range. In the outpatient setting, hypochloremia is independently associated with an increased mortality risk. This risk is dose-dependent where the lower the chloride level, the higher is the risk.