Prenatal and early childhood exposure to tetrachloroethylene (PCE)-contaminated drinking water and sleep quality in adulthood: a retrospective cohort study

Background Communities in Cape Cod, Massachusetts were exposed to tetrachloroethylene (PCE) through contaminated drinking water from 1969 to 1983. PCE exposure during adulthood has well-established neurotoxic effects; however, long-term impacts stemming from early life exposure, especially adverse effects on sleep quality, are not well understood. Methods The present analysis was based on data from the Cape Cod Health Study, a retrospective cohort study of the long-term neurotoxic impacts of early-life exposure to PCE-contaminated drinking water. Exposure to PCE-contaminated water was estimated using a validated leaching and transport model. Measures of sleep quality were obtained from self-administered questionnaires. Generalized estimating equations were used to generate risk ratios and 95% confidence intervals to estimate the association between early-life PCE exposure and sleep quality among 604 participants. Results Compared to unexposed participants, any PCE exposure during early life was associated with 1.57 times the risk of reporting breathing pauses during sleep (95% CI 0.92–2.68). Low-level exposure to PCE was associated with 1.50 times the risk of reporting sleep apnea or other sleep disorders (95% CI 0.78–2.89), while high levels of exposure had comparable risk compared to no exposure (RR = 0.94, 95% CI 0.50–1.79). Weak or no associations were observed for other sleep quality outcomes. In stratified analyses participants with mental illness and/or substance use disorder had increased risk ratios for short sleep duration associated with PCE exposure. Conclusion These findings suggest that early-life exposure to PCE may be associated with a moderate increase in the risk of reporting breathing pauses during sleep in adulthood and that a history of mental illness and/or substance use disorder may exacerbate the risk of short sleep duration.

Dental extraction, intensity-modulated radiotherapy of head and neck cancer, and osteoradionecrosis

Objective To seek evidence for osteoradionecrosis (ORN) after dental extractions before or after intensity-modulated radiotherapy (IMRT) for head and neck cancer (HNC). Methods Medline/PubMed, Embase, and Cochrane Library were searched from 2000 until 2020. Articles on HNC patients treated with IMRT and dental extractions were analyzed by two independent reviewers. The risk ratios (RR) and odds ratios (OR) for ORN related to extractions were calculated using Fisher’s exact test. A one-sample proportion test was used to assess the proportion of pre- versus post-IMRT extractions. Forest plots were used for the pooled RR and OR using a random-effects model. Results Seven of 630 publications with 875 patients were eligible. A total of 437 (49.9%) patients were treated with extractions before and 92 (10.5%) after IMRT. 28 (3.2%) suffered from ORN after IMRT. ORN was associated with extractions in 15 (53.6%) patients, eight related to extractions prior to and seven cases related to extractions after IMRT. The risk and odds for ORN favored pre-IMRT extractions (RR = 0.18, 95% CI: 0.04–0.74, p = 0.031, I2 = 0%, OR = 0.16, 95% CI: 0.03–0.99, p = 0.049, I2 = 0%). However, the prediction interval of the expected range of 95% of true effects included 1 for RR and OR. Conclusion Tooth extraction before IMRT is more common than after IMRT, but dental extractions before compared to extractions after IMRT have not been proven to reduce the incidence of ORN. Extractions of teeth before IMRT have to be balanced with any potential delay in initiating cancer therapy.

Predictors of COVID-19 Fatality: A Worldwide Analysis of the Pandemic over Time and in Latin America

SARS-CoV-2 has infected over one hundred million people worldwide and has affected Latin America particularly severely in terms of both cases and deaths. This study aims to determine the association between SARS-CoV-2 testing and COVID-19 fatality rate worldwide over 8 months and to examine how this relationship differs between Latin America and all other countries. This cross-sectional study used March 2021 data from 169 countries. Multivariate regressions predicted COVID-19 fatality (outcome) from the number of SARS-CoV-2 tests (exposure), while controlling for other predictors. Results for March 2021 were compared to results from June 2020. Additionally, results for Latin America were also compared to all other countries except Latin American for March 2021. SARS-CoV-2 testing was associated with a significant decrease in COVID-19 fatality rate in both June 2020 and March 2021 (RR = 0.92; 95% CI 0.87–0.96 and RR = 0.86; 95% CI 0.74–1.00, respectively). SARS-CoV-2 testing was associated with a significant decrease in COVID-19 fatality rate in Latin American countries but not in all other countries (RR = 0.45; 95% CI 0.23–0.89 and RR = 0.95; 95% CI 0.82–1.11, respectively). However, the difference between the risk ratios for June 2020 and March 2021 and between the risk ratios for Latin America and all other countries were not statistically significant. Increased SARS-CoV-2 testing may be a significant predictor of lower COVID-19 case fatality rate, specifically in Latin American countries, due to the existence of a strong association, which may have driven the worldwide results.

A Model to Estimate the Effect of International Traffic on Malaria Cases: The Case of Japan from 1999 to 2021

Aiming to identify the potentially reduced malaria cases by stagnation of international traffic after the COVID-19 pandemic, a longitudinal analysis of malaria cases as well as entries of Japanese and foreigners was conducted using data from 5 April 1999 to 30 September 2021 in Japan. Multivariable risk ratios were calculated with the Poison regression model as a predictive model of malaria cases by the number of entries for Japanese and foreigners. A generalized regression model was used to examine an association of time trend with entries for Japanese and foreigners using data before 2019, to estimate the potentially reduced number of entries after 2020. The potentially reduced number of malaria cases was estimated by the potentially reduced number of entries for Japanese and foreigners after 2020 using a multivariable Poison regression model. The multivariable risk ratio (95% confidence intervals) of malaria case numbers per 100,000 persons increment of entries per day was 3.41 (1.50–7.77) for Japanese and 1.47 (0.92–2.35) for foreigners. During 2020, a potential reduction of 28 (95% confidence limit: 22–34) malaria cases was estimated, which accounted for 58% (52–63%) of malaria cases in Japan. These finding suggest that the stagnation of international traffic during the COVID-19 pandemic reduced the number of malaria cases in Japan. This model may be helpful for countries without indigenous malaria to predict future trends of imported malaria cases.

Efficacy and Safety of Ocriplasmin Use for Vitreomacular Adhesion and Its Predictive Factors: A Systematic Review and Meta-Analysis

Symptomatic vitreomacular adhesion (sVMA) impedes visual acuity and quality. Ocriplasmin is a recombinant protease, which may be injected into the vitreous cavity to treat this condition, yet controversy remains with respect to its effectiveness and safety, particularly its patient selection standard. In this systematic review, the PubMed, Embase, and the Cochrane Library were searched to identify studies published prior to August 2020 on the impact of ocriplasmin treatment on VMA release, macular hole (MH) closure, and/or related adverse events (AEs). Data were pooled using a random-effects model. Risk ratios (RRs) with 95% CIs were calculated. Of 1,186 articles reviewed, 5 randomized controlled trials and 50 cohort studies were ultimately included, representing 4,159 patients. Ocriplasmin significantly increased the rate of VMA release (RR, 3.61; 95% CI, 1.99–6.53; 28 days after treatment) and MH closure (RR, 3.84; 95% CI, 1.62–9.08; 28 days after treatment) and was associated with visual function improvement. No increased risk for overall AEs was seen in ocriplasmin treatment. The proportion of VMA release and MH closure in patients was 0.50 and 0.36, respectively. VMA release was more likely in patients with absence of epiretinal membrane (ERM). Patients with smaller MH diameter were more likely to achieve MH closure. Evidence from included studies suggests that ocriplasmin is a suitable and safe approach for treating sVMA. ERM and MH status are important factors when considering ocriplasmin treatment.

Acupuncture Reduces the Risk of Dysphagia in Stroke Patients: A Propensity Score-Matched Cohort Study

Background: Post-stroke dysphagia (PSD) affects the quality of life in stroke patients, impairs their rehabilitation ability, and causes other complications following stroke. Currently, there is currently some understanding of PSD risk factors, but its protective factors remain largely unknown.Objective: To analyze the effects of acupuncture (AP) on dysphagia in stroke patients and explore its potential as a preventive therapy.Methods: Patients with a diagnosis of stroke from 2010 to 2019 were selected and followed until 2020, utilizing factors such as age, gender, stroke location, stroke type, and baseline comorbidity. To compare the incidence of dysphagia, equal numbers of stroke patients treated with and without AP (n = 1,809) were matched by 1:1 propensity scoring. The Cox proportional hazards model and Kaplan-Meier method were used to assess the risk of dysphagia as an outcome measure.Results: The stroke patients treated with AP had a lower risk of dysphagia after adjusting for age, gender, stroke location, stroke type, and baseline comorbidity [adjusted hazard ratio (AHR) = 0.43, 95% confidence interval = 0.37–0.49] compared with those in the non-AP cohort. AP also decreased the risk of PSD among different gender groups. The risk ratios were AHR = 0.45 and AHR = 0.33 for males and females, respectively. AP also reduced the risk for PSD among different age groups. The risk ratios were AHR = 0.20, AHR = 0.37, AHR = 0.41, and AHR = 0.45 for the 18–39, 40–59, 60–79, and >80 years-old groups. Regarding stroke types (ischemic, hemorrhagic, and mixed type), patients treated with AP had a lower risk (AHR = 0.47, 0.28 and 0.17, respectively). With respect to stroke location, the risk of PSD in AP-treated patients was decreased regardless of location: brain stem (AHR = 0.41), diencephalon (AHR = 0.13), or multiple lesions (AHR = 0.40), the risk of PSD in AP-treated patients was decreased. For all baseline comorbidities, AP attenuated the risk of dysphagia. The cumulative incidence of dysphagia was remarkably lower in the AP group than in the non-AP group (log-rank test, P = 0.000).Limitations: First, this was a single-center clinical retrospective study. Second, we did not classify the severity of stroke and dysphagia. Third, all data were extracted manually. Lastly, the sample size was relatively small. Thus, future studies with larger sample sizes are warranted to verify our findings.Conclusion: Acupuncture treatment attenuates the risk of dysphagia in stroke patients. Future research should increase the sample size and elaborate further on the details of the AP protocol.

Association between vaccination status and reported incidence of post-acute COVID-19 symptoms in Israel: a cross-sectional study of patients infected between March 2020 and November 2021

Background: Long COVID is a post-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection syndrome characterised by not recovering for several weeks or months following the acute episode. The effectiveness of COVID-19 vaccines against long-term symptoms of COVID19 is not well understood. We determined whether vaccination was associated with reporting long-term symptoms post-SARS-CoV-2 infection by comparing, among individuals previously infected with SARS-CoV-2, those who were vaccinated to those who were not, in terms of self-reported long-term symptoms. Methods: We invited individuals who were PCR tested for SARS-CoV-2 infection at participating hospitals between March 2020-June 2021 to fill an online questionnaire that included baseline demographics, details of their acute episode and information about symptoms they were currently experiencing. Using binomial regression, we compared vaccinated individuals with those unvaccinated in terms of self-reported symptoms post-acute infection. Results: Of 951 previously infected individuals who filled the survey 637(67%) were vaccinated. The most commonly reported symptoms were; fatigue (22%), headache (20%), weakness (13%), and persistent muscle pain (10%). After adjusting for follow-up time and baseline symptoms, fully vaccinated (2 or more doses) individuals were less likely than unvaccinated individuals to report any of these symptoms by 64%, 54%, 57%, and 68% respectively, (Risk ratios 0.36, 0.46, 0.43, 0.32, p<0.04 in the listed sequence). Conclusions: Vaccination with at least two doses of COVID-19 vaccine was associated with a substantial decrease in reporting the most common post-acute COVID19 symptoms. Our results suggest that, in addition to reducing the risk of acute illness, COVID-19 vaccination may have a protective effect against long COVID.

Glucose control after glucocorticoid administration in hospitalized patients – a retrospective analysis

Background Glucocorticoid (GC)-induced hyperglycemia is a frequent adverse effect in hospitalized patients. Guidelines recommend insulin treatment to a target range of 6–10 mmol/L (108–180 mg/dl), but efficacies of particular regimes have not been well-studied. Methods In this retrospective cohort study, hospitalized patients receiving GCs at the medical ward were analyzed by treatment (basal-bolus vs. bolus-only vs. pre-mixed insulin) and compared to a non-insulin-therapy reference group. Coefficients of glucose variation (CV), percentage of glucose readings in range (4–10 mmol/L (72–180 mg/dl)) and hypoglycemia (< 4 mmol/L (< 72 mg/dl)) were evaluated. Results Of 2424 hospitalized patients receiving systemic GCs, 875 (36%) developed GC-induced hyperglycemia. 427 patients (17%) had a previous diagnosis of diabetes. Adjusted relative risk ratios (RRR) for the top tertile of CV (> 29%) were 1.47 (95% Cl 1.01–2.15) for bolus-only insulin, 4.77 (95% CI 2.67–8.51) for basal-bolus insulin, and 4.98 (95% CI 2.02–12.31) for premixed insulin, respectively. Adjusted RRR for percentages of glucose readings in range were 0.98 (95% Cl 0.97–0.99) for basal-bolus insulin, 0.99 (95% Cl 0.98–1.00) for premixed insulin, and 1.01 (95% Cl 1.00–1.01) for bolus-only insulin, respectively. Adjusted RRR for hypoglycemia was 13.17 (95% Cl 4.35–39.90) for basal-bolus insulin, 8.92 (95% Cl 2.60–30.63) for premixed insulin, and 2.99 (95% Cl 1.01–8.87) for bolus-only insulin, respectively. Conclusions Current guidelines recommend a basal-bolus regimen for treatment of GC-induced hyperglycemia, but we found similar outcomes with pre-mixed and bolus-only insulin regimens. As GC-induced hyperglycemia is a frequent issue in hospitalized patients, it might be reasonable to prospectively study the ideal regimen.

Effectiveness of 17-OHP for Prevention of Recurrent Preterm Birth: A Retrospective Cohort Study

Objective 17-α-hydroxyprogesterone caproate (17-OHP) has been recommended by professional societies for the prevention of recurrent preterm birth, but subsequent clinical studies have reported conflicting efficacy results. This study aimed to contribute to the evidence base regarding the effectiveness of 17-OHP in clinical practice using real-world data. Study Design A total of 4,422 individuals meeting inclusion criteria representing recurrent spontaneous preterm birth (sPTB) were identified in a database of insurance claims, and 568 (12.8%) received 17-OHP. Crude and propensity score-matched recurrence rates and risk ratios (RRs) for the association of receiving 17-OHP on recurrent sPTB were calculated. Results Raw sPTB recurrence rates were higher among those treated versus not treated; after propensity score matching, no association was detected (26.3 vs. 23.8%, RR = 1.1, 95% CI: 0.9–1.4). Conclusion We failed to identify a beneficial effect of 17-OHP for the prevention of spontaneous recurrent preterm birth in our observational, U.S. based cohort. Key Points

Harboring Cnm-Expressing Streptococcus Mutans In The Oral Cavity Relates To Both Deep and Lobar Cerebral Microbleeds

Streptococcus mutans, a major cariogenic bacterium, expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, resulting in the impairment of blood brain barrier integrity followed by cerebral bleeding. We here examined the association of Cnm-positive S. mutans with cerebral microbleeds (CMBs) in acute stroke patients selected from a single-center registry database. Of 428 patients who received oral bacterial examinations among 3154 stroke patients, 326 patients who harbored S. mutans were identified. After excluding four patients without imaging data, we compared 72 patients with Cnm-positive S. mutans and 250 with Cnm-negative S. mutans. Deep, lobar and infratentorial CMBs were observed in 46 (63.9%), 36 (50.0%), 25 (34.7%) patients with Cnm-positive S. mutans and 144 (57.6%), 114 (45.6%), 101 (40.4%) with Cnm-negative S. mutans. Possession of Cnm-positive S. mutans was related to higher numbers of both deep and lobar, but not infratentorial, CMBs (risk ratios 1.57 [1.07‒2.30], deep; 5.44 [2.50‒11.85], lobar). Statistical significance persisted after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy (risk ratios 1.61 [1.14‒2.27], deep; 5.14 [2.78‒9.51], lobar). Our study indicated that reduction of Cnm-positive S. mutans may serve as a therapeutic approach for improving the prognosis of stroke patients.