Vaccine Coverage Associated With Ending a Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Wave: A Retrospective Longitudinal Analysis.

BACKGROUND: Two SARS-CoV-2 waves in Israel ended while a substantial number of individuals remained unvaccinated or partially vaccinated. The indirect protective effect of the first BNT162b2 vaccination campaign in Israel was evaluated between 22 December 2020 and 18 May 2021. METHODS: The daily percentage of new polymerase chain reaction (PCR)-confirmed SARS-CoV-2 cases among unvaccinated individuals was analyzed for trends. Major shifts were identified using piecewise linear regression analysis. At these shifts, the percentage of naturally vaccinated (past SARS-CoV-2 cases) and the percentage of actively vaccinated (by inoculation) individuals were weighted and summed to determine the percentage of natural and active vaccination (NAV). RESULTS: A first decline among unvaccinated individuals occurred during a lockdown period, when the percentage of NAV was 8.16%. The major decline occurred after the end of the lockdown when the percentage of NAV reached 52.05%. SARS-CoV-2 cases ultimately declined among unvaccinated individuals when the percentage of NAV reached 63.55%. During the study period, the Alpha variant was prevalent and the use of nonpharmaceutical interventions, including social distancing, existed to varying degrees. CONCLUSIONS: The vaccination campaign played a major role in the decline of SARS-CoV-2 infection among unvaccinated individuals, leading to the end of the first 2021 SARS-CoV-2 wave (Alpha variant) in Israel. Infection in unvaccinated individuals stopped when two-thirds of the population were naturally or actively vaccinated. Any change in characteristics of the virus or the population can lead to a new outbreak.

Effect of temperature on Escherichia coli bloodstream infection in a nationwide population-based study of incidence and resistance.

BACKGROUND: The incidence of Escherichia coli bloodstream infections (BSI) is high and increasing. We aimed to describe the effect of season and temperature on the incidence of E. coli BSI and antibiotic-resistant E. coli BSI and to determine differences by place of BSI onset. METHODS: All E. coli BSI in adult Israeli residents between January 1, 2018 and December 19, 2019 were included. We used the national database of mandatory BSI reports and outdoor temperature data. Monthly incidence and resistance were studied using multivariable negative binomial regressions with season (July-October vs. other) and temperature as covariates. RESULTS: We included 10,583 events, 9012 (85%) community onset (CO) and 1571 (15%) hospital onset (HO). For CO events, for each average monthly temperature increase of 5.5 °C, the monthly number of events increased by 6.2% (95% CI 1.6-11.1%, p = 0.008) and the monthly number of multidrug-resistant events increased by 4.9% (95% CI 0.3-9.7%, p = 0.04). The effect of season was not significant. For HO events, incidence of BSI and resistant BSI were not associated with temperature or season. CONCLUSION: Temperature increases the incidence of CO E. coli BSI and CO antibiotic-resistant E. coli BSI. Global warming threatens to increase the incidence of E. coli BSI.

One-year mortality and years of potential life lost following bloodstream infection among adults: A nation-wide population based study.

Background: Limited data exist on long-term consequences of bloodstream infections (BSIs). We aimed to examine incidence, 1-year mortality, and years of potential life lost (YPLL) following BSI. We estimated the relative contribution of hospital-onset BSI (HO-BSI) and antibiotic-resistant BSI to incidence, mortality and YPLL. Methods: We used data from Israel's national BSI surveillance system (covering eight sentinel bacteria, comprising 70% of all BSIs) and the national death registry. Adults with BSI between January 2018 and December 2019 were included. The outcomes were all-cause 30-day and 1-year mortality, with no adjustment for co-morbidities. We calculated the age-standardized mortality rate and YPLL using the Global Burden of Disease reference population and life expectancy tables. Findings: In total, 25,376 BSIs occurred over 2 years (mean adult population: 6,068,580). The annual incidence was 209·1 BSIs (95% CI 206·5-211·7) per 100,000 population. The case fatality rate was 25·6% (95% CI 25·0-26·2) at 30 days and 46·4% (95% CI 45·5-47·2) at 1 year. The hazard of death increased by 30% for each decade of age (HR=1·3 [95% CI 1·2-1·3]). The annual age-standardized mortality rate and YPLL per 100,000 were 50·8 (95% CI 49·7-51·9) and 1,012·6 (95% CI 986·9-1,038·3), respectively. HO-BSI (6,962 events) represented 27·4% (95% CI 26·9-28·0) of BSIs, 33·9% (95% CI 32·6-35·0) of deaths and 39·9% (95% CI 39·5-40·2) of YPLL. HO-BSI by drug-resistant bacteria (3,072 events) represented 12·1% (95% CI 11·7-12·5) of BSIs, 15·6% (95% CI 14·7-16·5) of deaths, and 18·4% (95% CI 18·1-18·7) of YPLL. Interpretation: One-year mortality following BSI is high. The burden of BSI is similar to that of ischemic stroke. HO-BSI and drug-resistant BSI contribute disproportionately to BSI mortality and YPLL. Funding: None.

Hospital-Onset Bloodstream Infections Caused by Eight Sentinel Bacteria: A Nationwide Study in Israel, 2018-2019.

Nationwide studies on hospital-onset bloodstream infections (HO-BSIs) are scarce. To describe incidence, mortality and antimicrobial resistance (AMR) of HO-BSI caused by eight sentinel bacteria in Israel, we used laboratory-based BSI surveillance data from 1 January 2018 to 31 December 2019. All hospitals reported positive blood cultures growing Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, Streptococcus pneumoniae, Staphylococcus aureus, Enterococcus faecalis and Enterococcus faecium. We calculated HO-BSI incidence and 14-day, 30-day and 1-year mortality in adults. We performed multivariable logistic regression to identify predictors of 30-day mortality. The study included 6752 HO-BSI events: K. pneumoniae (1659, 22.1%), E. coli (1491, 19.8%), S. aureus (1315, 17.5%), P. aeruginosa (1175, 15.6%), E. faecalis (778, 10.4%), A. baumannii (654, 8.7%), E. faecium (405, 5.4%) and S. pneumoniae (43, 0.6%). Overall incidence was 2.84/1000 admissions (95% CI: 2.77-2.91) and 6.88/10,000 patient-days (95% CI: 6.72-7.05). AMR isolates accounted for 44.2% of events. Fourteen-day, thirty-day and one-year mortality were 30.6% (95% CI: 28.5%-32.8%), 40.2% (95% CI: 38.2%-42.1%) and 66.5% (95% CI: 64.7%-68.3%), respectively. Organisms with highest risk for 30-day mortality (compared with E. coli) were A. baumannii (OR 2.85; 95% CI: 2.3-3.55), E. faecium (OR 2.16; 95% CI: 1.66-2.79) and S. pneumoniae (OR 2.36; 95% CI: 1.21-4.59). Mortality was higher in AMR isolates (OR 1.57; 95% CI: 1.4-1.77). This study highlights the incidence, associated high mortality and important role of antibiotic resistance in HO-BSI.

A nationwide population-based study of Escherichia coli bloodstream infections: incidence, antimicrobial resistance and mortality.

OBJECTIVES: Escherichia coli is the leading cause of bloodstream infection (BSI). The incidence of E. coli BSI caused by antibiotic-resistant strains is increasing. We aimed to describe the nationwide incidence and resistance profile of E. coli BSI in Israel and its impact on mortality, to compare E. coli BSI mortality with all-cause mortality, and community-onset with hospital-onset E. coli BSIs. METHODS: We used mandatory BSI surveillance reports submitted by all Israeli hospitals to the Ministry of Health and the national death registry. All E. coli BSIs from 1 January 2018 to 31 December 31 2019 in patients aged 18 and over were included. RESULTS: A total of 11 113 E. coli BSIs occurred in 10 218 patients; 85% (9012/10 583) were community onset. Median age was 76 (IQR 65-85), and 57% (6304/11 113) of cases occurred in women. The annual incidence was 92.5 per 100 000 population. Antibiotic resistance was frequent and significantly more common in hospital-onset than in community-onset BSI; 65% (1021/1571) vs. 45% (4049/9012) were multidrug-resistant (MDR) (p < 0.001). The case fatality rate (CFR) was higher following hospital-onset BSI than community-onset: 23% (276/1214) vs. 12% (926/7620) at 14 days, 31% (378/1214) vs. 16% (1244/7620) at 30 days, and 55% (418/766) vs. 34% (1645/4903) at 1 year (p < 0.001 for all comparisons). The 1-year CFR was 47% (1258/2707) for MDR vs. 28% (928/3281) for non-MDR (p < 0.001). The annual mortality rate was 31.0 per 100 000 population, comprising 4.2% (31.0/734.8) of all causes of deaths. DISCUSSION: E. coli BSI carries a high burden, with a large proportion of MDR isolates, which are associated with increased incidence and CFR.

Hybrid Deep Learning for Medication-Related Information Extraction From Clinical Texts in French: MedExt Algorithm Development Study.

BACKGROUND: Information related to patient medication is crucial for health care; however, up to 80% of the information resides solely in unstructured text. Manual extraction is difficult and time-consuming, and there is not a lot of research on natural language processing extracting medical information from unstructured text from French corpora. OBJECTIVE: We aimed to develop a system to extract medication-related information from clinical text written in French. METHODS: We developed a hybrid system combining an expert rule-based system, contextual word embedding (embedding for language model) trained on clinical notes, and a deep recurrent neural network (bidirectional long short term memory-conditional random field). The task consisted of extracting drug mentions and their related information (eg, dosage, frequency, duration, route, condition). We manually annotated 320 clinical notes from a French clinical data warehouse to train and evaluate the model. We compared the performance of our approach to those of standard approaches: rule-based or machine learning only and classic word embeddings. We evaluated the models using token-level recall, precision, and F-measure. RESULTS: The overall F-measure was 89.9% (precision 90.8; recall: 89.2) when combining expert rules and contextualized embeddings, compared to 88.1% (precision 89.5; recall 87.2) without expert rules or contextualized embeddings. The F-measures for each category were 95.3% for medication name, 64.4% for drug class mentions, 95.3% for dosage, 92.2% for frequency, 78.8% for duration, and 62.2% for condition of the intake. CONCLUSIONS: Associating expert rules, deep contextualized embedding, and deep neural networks improved medication information extraction. Our results revealed a synergy when associating expert knowledge and latent knowledge.

Hepatitis B Core-Related Antigen to Indicate High Viral Load: Systematic Review and Meta-Analysis of 10,397 Individual Participants.

BACKGROUND & AIMS: To eliminate hepatitis B virus (HBV) infection, scale-up of testing and treatment in resource-limited countries is crucial. However, access to nucleic acid testing to quantify HBV DNA, an essential test to examine treatment eligibility, remains severely limited. We assessed the performance of a novel immunoassay, HBV core-related antigen (HBcrAg), as a low-cost (less than US $15/assay) alternative to nucleic acid testing to indicate clinically important high viremia in chronic HBV patients infected with different genotypes. METHODS: We searched Medline, Embase, Scopus, and Web of Science databases through June 27, 2018. Three reviewers independently selected studies measuring HBV DNA and HBcrAg in the same blood samples. We contacted authors to provide individual participant data (IPD). We randomly allocated each IPD to a derivation or validation cohort. We applied optimal HBcrAg cut-off values derived from the derivation set to the validation set to estimate sensitivity/specificity. RESULTS: Of 74 eligible studies, IPD were obtained successfully for 60 studies (81%). Meta-analysis included 5591 IPD without antiviral therapy and 4806 treated with antivirals. In untreated patients, the pooled area under the receiver operating characteristic curve and optimal cut-off values were as follows: 0.88 (95% CI, 0.83-0.94) and 3.6 log U/mL to diagnose HBV DNA level of 2000 IU/mL or greater; and 0.96 (95% CI, 0.94-0.98) and 5.3 log U/mL for 200,000 IU/mL or greater, respectively. In the validation set, the sensitivity and specificity were 85.2% and 84.7% to diagnose HBV DNA level of 2000 IU/mL or greater, and 91.8% and 90.5% for 200,000 IU/mL or greater, respectively. The performance did not vary by HBV genotypes. In patients treated with anti-HBV therapy the correlation between HBcrAg and HBV DNA was poor. CONCLUSIONS: HBcrAg might be a useful serologic marker to indicate clinically important high viremia in treatment-naïve, HBV-infected patients.

French annual national observational study of 2015 outpatient and inpatient healthcare utilization by approximately half a million patients with previous heart failure diagnosis.

BACKGROUND: Heart failure management guidelines have been published, but the degree of adherence to these guidelines remains unknown. AIMS: To study in 2015 healthcare utilization and causes of death for people previously identified with heart failure. METHODS: The national health data system was used to identify adult general scheme (86% of the French population) hospitalized for heart failure between 2011 and 2014 or with only a long-term chronic disease allowance for heart failure. The frequency and median (interquartile range) of at least one healthcare use among those still alive in 2015 was calculated. RESULTS: A total of 499,296 adults (1.4% of the population) were included, and 429,853 were alive in 2015; median age 79 (68-86) years. At least one utilization was observed for a general practitioner in 95% of patients (median 8 [interquartile range 5-13] consultations), a cardiologist in 42% (2 [1-3]), a nurse in 78% (16 [4-100]), a loop diuretic in 64% (11 [8-12] dispensations), an aldosterone antagonist in 21% (8 [5-11]), a thiazide in 15% (7 [4-11]), a renin-angiotensin system inhibitor in 68% (11 [8-13]), a beta-blocker in 65% (11 [7-13]), a beta-blocker plus a renin-angiotensin system inhibitor in 57%, and a beta-blocker plus a renin-angiotensin system inhibitor plus an aldosterone antagonist in 37%. Hospitalization for heart failure was present for 8% (1 [1,2]). Higher levels of healthcare utilization were observed in the presence of hospitalization for heart failure before 2015. Among the 13.9% of people who died in 2015, heart failure accounted for 8% of causes, cardiovascular disease accounted for 39%. CONCLUSIONS: General practitioners and nurses are the main actors in the regular follow-up of patients with heart failure, whereas cardiologist consultations and dispensing of first-line treatments are insufficient with respect to guidelines.

Outpatient healthcare utilization 30 days before and after hospitalization for heart failure in France: Contribution of the national healthcare database (Systèmenationaldesdonnéesdesanté).

BACKGROUND: Guidelines have been published concerning patient management after hospitalization for heart failure. The French national healthcare database (Systèmenationaldesdonnéesdesanté; SNDS) can be used to compare these guidelines with real-life practice. AIMS: To study healthcare utilization 30 days before and after hospitalization for heart failure, and the variations induced by the exclusion of institutionalized patients, who are less exposed to outpatient healthcare utilization. METHODS: We identified the first hospitalization for heart failure in 2015 of adult beneficiaries of the health insurance schemes covering 88% of the French population, who were alive 30 days after hospitalization. Outpatient healthcare utilization rates during the 30 days after hospitalization and the median times to outpatient care, together with their interquartile ranges, were described for all patients, and for a subgroup excluding institutionalized patients. RESULTS: Among the 104,984 patients included (mean age 79 years; 52% women), 74% were non-institutionalized (mean age 78 years; 47% women). The frequencies of at least one consultation after hospitalization and the median times to consultation were 69% (total sample) vs. 78% (subgroup excluding institutionalized patients) and 8 days (interquartile range 3; 16) vs. 7 days (3; 15) for general practitioners, 20% vs. 21% and 14 days (7; 23) vs. 16 days (9; 24) for cardiologists and 58% vs. 69% and 3 days (1; 9) vs. 2 days (1; 7) for nurses, with reimbursement of diuretics in 77% vs. 86%, angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in 48% vs. 55% and beta-blockers in 55% vs. 63%. Departmental variations, excluding institutionalized patients, were large: general practice consultations (interquartile range 74%; 83%), cardiology consultations (11%; 23%) and nursing care (68%; 77%). CONCLUSIONS: Low outpatient healthcare utilization rates, long intervals to first healthcare utilization and departmental variations indicate a mismatch between guidelines and real-life practice, which is accentuated when including institutionalized patients.

High prevalence and poor linkage to care of transfusion-transmitted infections among blood donors in Dar-es-Salaam, Tanzania.

Blood transfusion is one of the most commonly relied upon therapies in sub-Saharan Africa. Existing safeguards recommended include systematic screening for transfusion-transmitted infections and restricted voluntary nonremunerated blood donor selection. We report the transfusion-transmitted infection screening and notification practice at a large urban blood transfusion centre in Dar-es-Salaam, Tanzania. Between October 2016 and March 2017 anonymized records of all donors registered at the blood transfusion unit were accessed to retrospectively note demographic information, donor status, first-time status, transfusion-transmitted infection result and notification. 6402 consecutive donors were screened for transfusion-transmitted infections; the majority were family/replacement blood donors (88.0%) and male (83.8%). Overall transfusion-transmitted infections prevalence was 8.4% (95% CI 7.8-9.1), with hepatitis B being the most prevalent infection (4.1% (95% CI 3.6-4.6)). Transfusion-transmitted infections were more common in family/replacement blood donors (9.0% (95% CI 8.3-9.8)) as compared to voluntary nonremunerated blood donor (4.1% (95% CI 2.8-5.7)). A minority of infected-donors were notified of a positive result (8.5% (95% CI 6.3-11.2)). Although transfusion-transmitted infections are more prevalent among family/replacement blood donors, overall risk of transfusion-transmitted infections across all groups is considerable. In addition, existing efforts to notify donors of a positive transfusion-transmitted infection are poor. Future policies must focus on improving linkage to care for newly diagnosed patients with transfusion-transmitted infections.

Signal detection on a patient cohort: A disproportionality analysis of the ANRS CO22 HEPATHER cohort to identify associations between direct acting antivirals and adverse events in patients with hepatitis C virus chronic infection.

PURPOSE: Our aim was to explore a signal detection method for early identification of potential adverse drug reactions (ADRs) in a patient cohort. METHODS: ANRS CO22 HEPATHER is a French multicentre prospective observational cohort started in 2012. The cohort includes patients with chronic hepatitis C virus (HCV) infection with reports of all adverse events (AEs) occurring in patients exposed to HCV drugs. We applied a disproportionality method, which calculated a measure of association, the Bayesian information component (IC), for each drug-AE pair. Information components were continuously updated and a positive drug-AE association was detected when the lower limit of an IC 95% credible interval (95% CI) exceeded 0. We illustrate how the method could result in timely detection of photosensitivity reaction with simeprevir use. RESULTS: By August 28, 2016, 6600 patients with HCV infection had been treated or were undergoing current HCV treatment, and 3464 experienced at least one AE for a total of 12 720 reported AEs. We detected 52 positive drug-AE associations, including 44 that were known ADRs based on the summary of product characteristics. The association between simeprevir and photosensitivity reaction was detected on June 4, 2014. At this date, 68 patients had received simeprevir and 6 photosensitivity reaction (4 during simeprevir treatment) had been reported for an estimated IC of 1.90, 95% CI, 0.20-3.61. CONCLUSIONS: The disproportionality method can help with early detection of potential ADRs in patient cohorts. Detected associations need to be confirmed by a review of clinical data.

Dynamic contrast-enhanced imaging in localizing local recurrence of prostate cancer after radiotherapy: Limited added value for readers of varying level of experience.

BACKGROUND: The incremental value of dynamic contrast-enhanced (DCE) imaging in localizing radiorecurrent prostate cancer is uncertain. PURPOSE: To assess the added-value of DCE imaging to the combination T2 -weighted imaging (T2 W)+diffusion-weighted imaging (DWI) in detecting locally radiorecurrent prostate cancer (PCa), by radiologists with different levels of experience. STUDY TYPE: Analytic retrospective study. POPULATION: In all, 52 men with biological suspected PCa recurrence after radiotherapy were retrospectively included. FIELD STRENGTH/SEQUENCE: All men underwent prostatic MRI (1.5T or 3T), including T2 W, DWI, and DCE imagings, before biopsies. ASSESSMENT: Two junior (6 months' experience) and two senior readers (more than 3 years' experience) independently assigned a Likert score for each prostatic sextant on T2 W+DW+DCE imagings, then on T2 W+DW imagings, 4 weeks later. STATISTICAL TESTS: The reference standard was prostatic biopsies. For two levels of positivity of Likert score, 3/5 and 4/5, sensitivity, specificity, area under the receiver operating curve (AUC), and interreader agreement were compared. RESULTS: T2 W+DWI+DCE and T2 W+DWI imaging had similar AUC at lobe and sextant level (0.853-0.946 vs. 0.819-0.955, P from 0.071-0.534). Using a Likert score ≥4/5, T2 W+DWI+DCE significantly improved the sensitivity for junior readers at the patient, lobe, and sextant level (40-80% vs. 22-66%, P < 0.0001-0.041). Sensitivity was not significantly modified with DCE imaging for senior readers (54-95% vs. 50-91%, P from 0.074-1). Specificity was not modified for all readers (50-100% vs. 50%-100%, P from 0.134-1). DCE imaging improved interreader agreement for a Likert score ≥4/5 (kappa from 0.6-0.73 vs. 0.38-0.73). DATA CONCLUSION: The addition of DCE imaging did not significantly improve accuracy in recurrent PCa detection after radiotherapy, whatever the level of experience of the readers. However, the addition of DCE imaging slightly improved the sensitivity for less-experienced readers and increased their diagnostic confidence. LEVEL OF EVIDENCE: 3 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2018;48:1012-1023.

Comparing Inpatient Satisfaction Collected via a Web-Based Questionnaire Self-Completion and Through a Telephone Interview: An Ancillary Study of the SENTIPAT Randomized Controlled Trial.

BACKGROUND: Assessing the satisfaction of patients about the health care they have received is relatively common nowadays. In France, the satisfaction questionnaire, I-Satis, is deployed in each institution admitting inpatients. Internet self-completion and telephone interview are the two modes of administration for collecting inpatient satisfaction that have never been compared in a multicenter randomized experiment involving a substantial number of patients. OBJECTIVE: The objective of this study was to compare two modes of survey administration for collecting inpatient satisfaction: Internet self-completion and telephone interview. METHODS: In the multicenter SENTIPAT (acronym for the concept of sentinel patients, ie, patients who would voluntarily report their health evolution on a dedicated website) randomized controlled trial, patients who were discharged from the hospital to home and had an Internet connection at home were enrolled between February 2013 and September 2014. They were randomized to either self-complete a set of questionnaires using a dedicated website or to provide answers to the same questionnaires administered during a telephone interview. As recommended by French authorities, the analysis of I-Satis satisfaction questionnaire involved all inpatients with a length of stay (LOS), including at least two nights. Participation rates, questionnaire consistency (measured using Cronbach alpha coefficient), and satisfaction scores were compared in the two groups. RESULTS: A total of 1680 eligible patients were randomized to the Internet group (n=840) or the telephone group (n=840). The analysis of I-Satis concerned 392 and 389 patients fulfilling the minimum LOS required in the Internet and telephone group, respectively. There were 39.3% (154/392) and 88.4% (344/389) responders in the Internet and telephone group, respectively (P<.001), with similar baseline variables. Internal consistency of the global satisfaction score was higher (P=.03) in the Internet group (Cronbach alpha estimate=.89; 95% CI 0.86-0.91) than in the telephone group (Cronbach alpha estimate=.84; 95% CI 0.79-0.87). The mean global satisfaction score was lower (P=.03) in the Internet group (68.9; 95% CI 66.4-71.4) than in the telephone group (72.1; 95% CI 70.4-74.6), with a corresponding effect size of the difference at -0.253. CONCLUSIONS: The lower response rate issued from Internet administration should be balanced with a likely improved quality in satisfaction estimates, when compared with telephone administration, for which an interviewer effect cannot be excluded. TRIAL REGISTRATION: Clinicaltrials.gov NCT01769261 ; http://clinicaltrials.gov/ct2/show/NCT01769261 (Archived by WebCite at http://www.webcitation.org/6ZDF5lA41).