Time-varying association of acute and post-acute COVID-19 with new-onset diabetes mellitus among hospitalized and non-hospitalized patients.

INTRODUCTION: Previous studies have shown disruption of glycometabolic control and new diabetes mellitus (DM) diagnosis among patients with COVID-19. It is still unclear how the association of COVID-19 and new-onset DM may be modified by disease severity or vary over time, during acute and post-acute phases. RESEARCH DESIGN AND METHODS: In this retrospective matched cohort study, 157 936 patients with COVID-19 (aged ≥25 years, diagnosis date between March 01, 2020 and August 31, 2021) were compared with individuals without COVID-19, separately for non-hospitalized, hospitalized, and severe hospitalized patients. Stratified Cox proportional hazards models, with changing baseline time (starting at the date of COVID-19 diagnosis, and at 1, 2, 3, and 4 months afterwards), were used to evaluate the occurrence of new DM in relation to COVID-19 infection in different time frames-from each landmark date until end of study. RESULTS: During mean follow-up time of 10.9 months, there were 1145 (0.72%) new diagnoses of DM compared with 1013 (0.64%) in the individuals without COVID-19 (p=0.004). Non-hospitalized patients with COVID-19 were not at higher risk of new DM neither during the acute phase nor afterward. Hospitalized patients with COVID-19 had a higher risk of developing DM, with the highest risk among severe hospitalized patients. This risk among hospitalized patients was highest in the acute phase (HR 2.47 (95% CI 1.86 to 3.29)), attenuated over time, but remained significant at 4-month landmark analysis (HR 1.60 (95% CI 1.12 to 2.29)). CONCLUSIONS: Acute and post-acute COVID-19 were associated with new DM only among hospitalized patients, with the highest risk among those hospitalized with severe disease. Those patients should be followed and monitored post-discharge for new DM. Patients who were not hospitalized did not have higher risk of new-onset DM.

Failure to Detect Leishmania in the Blood of Patients with Old-World Cutaneous Leishmaniasis: Implications for Blood Donation.

Cutaneous leishmaniasis (CL) is endemic in Israel, caused mainly by Leishmania major (L. major) and L. tropica. In addition, returning travelers import another leishmanial species such as L. braziliensis. Although we are dealing with a skin disease, the blood bank in Israel does not accept blood donations from people infected with CL in cases of multiple lesions due to the possibility of transfusion. Our purpose was to investigate the prevalence of Leishmania in the blood of patients with active or previous CL. This pilot study screened patients with active or previous CL for parasites in their blood. All patients were infected in Israel or were returning travelers with leishmaniasis acquired in Latin America. Patients were seen at the Sheba Medical Center. In addition, patients were seen at their homes in L. tropica and L. major endemic regions in Israel. Blood samples were taken from each patient for culture and polymerase chain reaction (PCR). Altogether 62 blood samples were examined (L. tropica = 26, L. major = 33, and L. braziliensis = 3). Twenty-seven patients had an active disease and 35 were recovered. All blood cultures and PCR were negative for parasites except one blood sample that was PCR positive for L. braziliensis. The findings of our study, although a small sample, suggest that people with active or recent CL caused by L. major and L. tropica, do not harbor parasites in their blood. Thus, their exclusion from blood donation should be revisited. Further studies are needed with larger sample size and highly sensitive tests.

The impact of COVID-19 pandemic on emergency department visits and associated mortality during 14 months of the pandemic in Israel.

BACKGROUND: A substantial drop in emergency department (ED) visit volume was previously demonstrated at the onset of the COVID-19 pandemic. OBJECTIVE: To examine changes in the number of non-COVID adult ED visits and their associated 30-day mortality during 14 months of the pandemic in Israel. METHODS: This is a retrospective cohort study including 1,285,270 adult ED visits between 1st March, 2018 and 30th April, 2021 to the internal and surgical EDS in eight general hospitals of the largest healthcare organization in Israel. The 14 months of the pandemic period (March 2020-April 2021) were divided into seven periods according to dates of the three lockdowns. Exposure to each of these periods was compared to the parallel period during the two previous years. March 2020-April 2021 was compared to the parallel periods in 2018 and 2019. RESULTS: During the pandemic period, the largest decline in ED visits (44.6% and 50.9% for internal and surgical EDs, respectively) and the highest excess 30-day mortality following an ED visit (internal EDs Adjusted OR (ORadj), 1.49; 95% CI, 1.34-1.66 and surgical EDs: ORadj 1.50; CI, 1.16-1.94) were 95%, observed during the first lockdown. Both gradually levelled-off subsequently until near-normalization was reached in March-April 2021 for both parameters. CONCLUSIONS: A substantial decline in non-COVID ED visits and excess mortality at the beginning of the pandemic, are probably the results of social distancing restrictions alongside patients' fear of exposure to COVID-19, which gradually moderated thereafter, until near normalization was reached after 14 months. Gradual return to pre-pandemic ED utilization patterns were noticed as the population and the healthcare system acclimatize to life alongside COVID.

Vitamin D deficiency is associated with higher risks for SARS-CoV-2 infection and COVID-19 severity: a retrospective case-control study.

Robust evidence of whether vitamin D deficiency is associated with COVID-19 infection and its severity is still lacking. The aim of the study was to evaluate the association between vitamin D levels and the risks of SARS-CoV-2 infection and severe disease in those infected. A retrospective study was carried out among members of Clalit Health Services (CHS), the largest healthcare organization in Israel, between March 1 and October 31, 2020. We created two matched case-control groups of individuals for which vitamin D levels and body mass index (BMI) were available before the pandemic: group (A), in which 41,757 individuals with positive SARS-CoV-2 PCR tests were matched with 417,570 control individuals without evidence of infection, and group (B), in which 2533 patients hospitalized in severe condition for COVID-19 were matched with 2533 patients who were tested positive for SARS-CoV-2, but were not hospitalized. Conditional logistic models were fitted in each of the groups to assess the association between vitamin D levels and outcome. An inverse correlation was demonstrated between the level of vitamin D and the risks of SARS-CoV-2 infection and of severe disease in those infected. Patients with very low vitamin D levels (< 30 nmol/L) had the highest risks for SARS-CoV-2 infection and also for severe COVID-19 when infected-OR 1.246 [95% CI 1.210-1.304] and 1.513 [95% CI 1.230-1.861], respectively. In this large observational population study, we show a significant association between vitamin D deficiency and the risks of SARS-CoV-2 infection and of severe disease in those infected.

Identification of drugs associated with reduced severity of COVID-19 - a case-control study in a large population.

Background: Until coronavirus disease 2019 (COVID-19) drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Toward this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. Methods: Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18 to 95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. Results: Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI [0.058 to 0.458], p<0.001), ezetimibe (OR=0.488, 95% CI [0.377 to 0.622], p<0.001), rosuvastatin (OR=0.673, 95% CI [0.596 to 0.758], p<0.001), flecainide (OR=0.301, 95% CI [0.118 to 0.641], p<0.001), and vitamin D (OR=0.869, 95% CI [0.792 to 0.954], p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. Conclusions: Ubiquinone, ezetimibe, and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. Funding: This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.

COVID-19 Prevalence and Mortality Among Schizophrenia Patients: A Large-Scale Retrospective Cohort Study.

OBJECTIVE: Individuals with schizophrenia may be at an increased risk for COVID-19 morbidity due to the disease characteristics. In this study, we aimed to explore the odds of significant COVID-19 morbidity and mortality among schizophrenia patients while controlling for potential sociodemographic and medical confounders. METHODS: Schizophrenia patients and age-and-sex matched controls (total n = 51 078) were assessed for frequency of COVID-19 positivity, hospitalizations, and mortality. The odds for COVID-19-associated hospitalization and mortality were calculated using logistic regression models, while controlling for age, sex, marital status, sector, socioeconomic status, diabetes, ischemic heart disease, hypertension, hyperlipidemia, obesity, smoking, and chronic obstructive pulmonary disease. RESULTS: Individuals with schizophrenia were less likely to test positive for COVID-19; however, they were twice as likely to be hospitalized for COVID-19 (OR 2.15 95% CI 1.63-2.82, P < .0001), even after controlling for sociodemographic and clinical risk factors (OR 1.88 95% CI 1.39-2.55, P < .0001). Furthermore, they were 3 times more likely to experience COVID-19 mortality (OR 3.27 95% CI 1.39-7.68, P < .0001), compared to controls. CONCLUSIONS: We found evidence of associations between schizophrenia and increased COVID-19 morbidity and mortality compared to controls regardless of sociodemographic and medical factors. As these patients present with a combination of potential risk factors for mortality, efforts should be made to minimize the effects of the pandemic on this vulnerable population.

Identification of drugs associated with reduced severity of COVID-19: A case-control study in a large population.

BACKGROUND: Until COVID-19 drugs specifically developed to treat COVID-19 become more widely accessible, it is crucial to identify whether existing medications have a protective effect against severe disease. Towards this objective, we conducted a large population study in Clalit Health Services (CHS), the largest healthcare provider in Israel, insuring over 4.7 million members. METHODS: Two case-control matched cohorts were assembled to assess which medications, acquired in the last month, decreased the risk of COVID-19 hospitalization. Case patients were adults aged 18-95 hospitalized for COVID-19. In the first cohort, five control patients, from the general population, were matched to each case (n=6202); in the second cohort, two non-hospitalized SARS-CoV-2 positive control patients were matched to each case (n=6919). The outcome measures for a medication were: odds ratio (OR) for hospitalization, 95% confidence interval (CI), and the p-value, using Fisher's exact test. False discovery rate was used to adjust for multiple testing. RESULTS: Medications associated with most significantly reduced odds for COVID-19 hospitalization include: ubiquinone (OR=0.185, 95% CI (0.058 to 0.458), p<0.001), ezetimibe (OR=0.488, 95% CI ((0.377 to 0.622)), p<0.001), rosuvastatin (OR=0.673, 95% CI (0.596 to 0.758), p<0.001), flecainide (OR=0.301, 95% CI (0.118 to 0.641), p<0.001), and vitamin D (OR=0.869, 95% CI (0.792 to 0.954), p<0.003). Remarkably, acquisition of artificial tears, eye care wipes, and several ophthalmological products were also associated with decreased risk for hospitalization. CONCLUSIONS: Ubiquinone, ezetimibe and rosuvastatin, all related to the cholesterol synthesis pathway were associated with reduced hospitalization risk. These findings point to a promising protective effect which should be further investigated in controlled, prospective studies. FUNDING: This research was supported in part by the Intramural Research Program of the National Institutes of Health, NCI.

The Utilization of an Insertable Cardiac Monitor in a Child With Pallid Breath-Holding Spells.

BACKGROUND: Pacing can be a successful treatment for pallid breath-holding spells, primarily in individuals with severe bradycardia. PATIENT DESCRIPTION: We describe an 18-month-old girl experiencing severe pallid breath-holding spells in whom repeated electrocardiographic, Holter, and electroencephalographic monitoring tests were all normal. RESULTS: Using a subcutaneous insertable cardiac monitor, severe bradycardia was detected during one of this girl's episodes. This finding led to a pacemaker implantation. Subsequently, her breath-holding spells completely resolved. CONCLUSION: This child illustrates the ability of the insertable cardiac monitor to help and diagnose arrhythmias in children with unresolved clinical findings. The ability to implant it with a minimal scar makes it ideal for uncooperative individuals with relative few and unexpected episodes that are hard to diagnose.

The Price of a Neglected Zoonosis: Case-Control Study to Estimate Healthcare Utilization Costs of Human Brucellosis.

Human brucellosis has reemerged as a serious public health threat to the Bedouin population of southern Israel in recent years. Little is known about its economic implications derived from elevated healthcare utilization (HCU). Our objective was to estimate the HCU costs associated with human brucellosis from the insurer perspective. A case-control retrospective study was conducted among Clalit Health Services (CHS) enrollees. Brucellosis cases were defined as individuals that were diagnosed with brucellosis at the Clinical Microbiology Laboratory of Soroka University Medical Center in the 2010-2012 period (n = 470). Control subjects were randomly selected and matched 1:3 by age, sex, clinic, and primary physician (n = 1,410). HCU data, demographic characteristics and comorbidities were obtained from CHS computerized database. Mean±SD age of the brucellosis cases was 26.6±17.6 years. 63% were male and 85% were Bedouins. No significant difference in Charlson comorbidity index was found between brucellosis cases and controls (0.41 vs. 0.45, respectively, P = 0.391). Before diagnosis (baseline), the average total annual HCU cost of brucellosis cases was slightly yet significantly higher than that of the control group ($439 vs. $382, P<0.05), however, no significant differences were found at baseline in the predominant components of HCU, i.e. hospitalizations, diagnostic procedures, and medications. At the year following diagnosis, the average total annual HCU costs of brucellosis cases was significantly higher than that of controls ($1,327 vs. $380, respectively, P<0.001). Most of the difference stems from 7.9 times higher hospitalization costs (p<0.001). Additional elevated costs were 3.6 times higher laboratory tests (P<0.001), 2.8 times higher emergency room visits (P<0.001), 1.8 times higher medication (P<0.001) and 1.3 times higher diagnostic procedures (P<0.001). We conclude that human brucellosis is associated with elevated HCU costs. Considering these results in cost-effective analyses may be crucial for both reducing health inequities and optimal allocation of health systems' scarce resources.

Metabolic changes in immigrants from Africa to a Western country: time-lag effects of 20 years since immigration.

BACKGROUND: An increase in the prevalence of type 2 diabetes mellitus occurs in immigrants from developing regions to Western countries. However, the dynamics of these transitions in relation to the duration of residence in the new environment are not clearly defined. METHODS: Data concerning cardiovascular risk factors were retrospectively extracted from medical charts of 736 Ethiopian immigrants and 575 randomly-chosen, age and sex matched non-Ethiopian subjects ("reference group"). Ethiopian immigrants were designated "established" (≥ 20 years of residence), "intermediate" (10-15 years of residence), or "recent" (<10 years of residence). RESULTS: Compared to non-Ethiopians, the age- and sex-adjusted odds ratio (OR) for diabetes was 1.00 (95%CI: 0.66-1.49) for established, 0.55 (95%CI: 0.29-1.03) for intermediate, and 0.15 (95%CI: 0.04-0.50) for recent immigrants (P < 0.001). The corresponding OR for hypertension was 0.94 (95%CI: 0.68-1.31), 0.42 (95%CI: 0.26-0.69), and 0.14 (95%CI: 0.06-0.30) for the established, intermediate, and recent immigrants respectively (P < 0.001). In contrast to the gradual increase in prevalence of diabetes and hypertension, the Ethiopian immigrants maintained their lower body mass index (BMI) (28.7 ± 5 vs 25.5 ± 5 kg/m(2) respectively, P < 0.001) and serum low-density-lipoprotein cholesterol (129 ± 36 vs 118 ± 34 mg/dL, P < 0.001) compared to the non-Ethiopians even after 20 years of residence in Israel. CONCLUSIONS: The prevalence of diabetes and hypertension among the immigrants increased to about half that of the local population within 15 years and became equal to that of the local population after a time-lag of 20 years. These metabolic derangements occurred despite maintaining desirable BMI levels, reinforcing the need for re-defining optimal BMI ranges in relation to the ethnic origin.

Quality of life at the Dead Sea region: the lower the better? An observational study.

BACKGROUND: The Dead Sea region, the lowest in the world at 410 meters below sea level, is considered a potent climatotherapy center for the treatment of different chronic diseases. OBJECTIVE: To assess the prevalence of chronic diseases and the quality of life of residents of the Dead Sea region compared with residents of the Ramat Negev region, which has a similar climate, but is situated 600 meters above sea level. METHODS: An observational study based on a self-administered questionnaire. Data were collected from kibbutz (communal settlement) members in both regions. Residents of the Dead Sea were the study group and of Ramat Negev were the control group. We compared demographic characteristics, the prevalence of different chronic diseases and health-related quality of life (HRQOL) using the SF-36 questionnaire. RESULTS: There was a higher prevalence of skin nevi and non-inflammatory rheumatic diseases (NIRD) among Dead Sea residents, but they had significantly higher HRQOL mean scores in general health (68.7 ± 21 vs. 64.4 ± 22, p = 0.023) and vitality (64.7 ± 17.9 vs. 59.6 ± 17.3, p = 0.001), as well as significantly higher summary scores: physical component score (80.7 ± 18.2 vs. 78 ± 18.6, p = 0.042), and mental component score (79 ± 16.4 vs. 77.2 ± 15, p = 0.02). These results did not change after adjusting for social-demographic characteristics, health-related habits, and chronic diseases. CONCLUSIONS: No significant difference between the groups was found in the prevalence of most chronic diseases, except for higher rates of skin nevi and NIRD among Dead Sea residents. HRQOL was significantly higher among Dead Sea residents, both healthy or with chronic disease.

Nonattendance in obstetrics and gynecology patients.

BACKGROUND: Nonattendance for obstetrics and gynecology (OB/GYN) appointments disrupts medical care and leads to misuse of valuable resources. We investigated factors associated with nonattendance in an outpatient OB/GYN clinic. METHODS: Nonattendance was examined for a period of 1 year in first-time visitors of an ambulatory OB/GYN clinic. The effects of age, population sector, the treating physician, waiting time, and timing of the appointment on the proportions of nonattendance were assessed. Chi(2) tests and logistic regression were used for simple and multiple regression models. RESULTS: A total of 8,883 visits were included (median age 36 years). The proportion of nonattendance was 30.1%: 19.9% among rural Jewish, 30.5% in urban Jewish, and 36% in Bedouins (p < 0.001). Nonattendance increased from 26.6% among those waiting up to 1 week to 32.3% among those who waited more than 15 days (p < 0.001) and decreased with age (p < 0.001). A multiple logistic regression model demonstrated that age, population sector and waiting time for an appointment were significantly associated with nonattendance. CONCLUSION: Nonattendance in OB/GYN patients is independently associated with age, population sector and waiting time for an appointment. It is suggested that various solutions should be carefully introduced assessed regarding routine patient scheduling in OB/GYN clinics.