Real-World Coverage With Influenza, Pneumococcal, and Herpes Zoster Vaccines Among Patients With Rheumatic Diseases in a Nationwide Healthcare Plan.

OBJECTIVE: Vaccination against preventable infections is important for the management of rheumatic diseases (RDs). This study assessed the vaccination coverage and predictors among patients with RDs using real-world data from Israel. METHODS: This retrospective cross-sectional study, based on a Maccabi Healthcare Services database, included adult patients diagnosed with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and systemic lupus erythematosus (SLE), as of April 30, 2019. Age-specific vaccination coverage for influenza (past year), pneumococcal (23-valent pneumococcal polysaccharide vaccine [PPSV23] and/or 13-valent pneumococcal conjugate vaccine [PCV13]), and live-attenuated herpes zoster (HZ) vaccines (past 5 years) was reported. Logistic regression was used to investigate predictors of vaccination. RESULTS: The study included 14,528 patients (RA: n = 6932; PsA: n = 4395; SLE: n = 1951; > 1 condition: n = 1250). Influenza vaccine coverage among patients with RA, PsA, and SLE was 45.1%, 36.2%, and 33.7%, respectively. For PPSV23, corresponding rates were 19.6%, 16.2%, and 12.6%, respectively. In the elderly population (≥ 65 years), 63.2% had influenza vaccine in the past year and 83.4% had a PPSV23 vaccine in the past 5 years or at age ≥ 65. For PCV13 and HZ, coverage in the overall study population was low at 4.8% and 3.6%, respectively. Central residence and treatment with corticosteroids and biologic or targeted synthetic disease-modifying antirheumatic drugs within the past 5 years were significant predictors of vaccination coverage across all vaccines (P < 0.05). Other predictors varied by vaccine, including female sex (influenza, PPSV23, PCV13), age (influenza, PPSV23), chronic comorbidities (influenza, PPSV23, PCV13), shorter disease duration (PCV13), and high socioeconomic status (PCV13, HZ). CONCLUSION: This study demonstrated suboptimal coverage of influenza, pneumococcal, and HZ vaccination in patients with RA, PsA, and SLE, in particular among younger adults in Israel.

Pharmaceutical Agents as Potential Drivers in the Development of Early-Onset Colorectal Cancer: Case-Control Study.

BACKGROUND: The incidence of early-onset colorectal cancer (EOCRC) rose abruptly in the mid 1990s, is continuing to increase, and has now been noted in many countries. By 2030, 25% of American patients diagnosed with rectal cancer will be 49 years or younger. The large majority of EOCRC cases are not found in patients with germline cancer susceptibility mutations (eg, Lynch syndrome) or inflammatory bowel disease. Thus, environmental or lifestyle factors are suspected drivers. Obesity, sedentary lifestyle, diabetes mellitus, smoking, alcohol, or antibiotics affecting the gut microbiome have been proposed. However, these factors, which have been present since the 1950s, have not yet been conclusively linked to the abrupt increase in EOCRC. The sharp increase suggests the introduction of a new risk factor for young people. We hypothesized that the driver may be an off-target effect of a pharmaceutical agent (ie, one requiring regulatory approval before its use in the general population or an off-label use of a previously approved agent) in a genetically susceptible subgroup of young adults. If a pharmaceutical agent is an EOCRC driving factor, regulatory risk mitigation strategies could be used. OBJECTIVE: We aimed to evaluate the possibility that pharmaceutical agents serve as risk factors for EOCRC. METHODS: We conducted a case-control study. Data including demographics, comorbidities, and complete medication dispensing history were obtained from the electronic medical records database of Maccabi Healthcare Services, a state-mandated health provider covering 26% of the Israeli population. The participants included 941 patients with EOCRC (≤50 years of age) diagnosed during 2001-2019 who were density matched at a ratio of 1:10 with 9410 control patients. Patients with inflammatory bowel disease and those with a known inherited cancer susceptibility syndrome were excluded. An advanced machine learning algorithm based on gradient boosted decision trees coupled with Bayesian model optimization and repeated data sampling was used to sort through the very high-dimensional drug dispensing data to identify specific medication groups that were consistently linked with EOCRC while allowing for synergistic or antagonistic interactions between medications. Odds ratios for the identified medication classes were obtained from a conditional logistic regression model. RESULTS: Out of more than 800 medication classes, we identified several classes that were consistently associated with EOCRC risk across independently trained models. Interactions between medication groups did not seem to substantially affect the risk. In our analysis, drug groups that were consistently positively associated with EOCRC included beta blockers and valerian (Valeriana officinalis). Antibiotics were not consistently associated with EOCRC risk. CONCLUSIONS: Our analysis suggests that the development of EOCRC may be correlated with prior use of specific medications. Additional analyses should be used to validate the results. The mechanism of action inducing EOCRC by candidate pharmaceutical agents will then need to be determined.

Re-evaluating Perinatal Group B Streptococcal screening in Israel - Is it time for a change in policy?

Group B streptococcal early-onset disease (EOGBSD) is a significant cause of morbidity and fatality in newborns. Current policy in Israel is risk-based management. Our aim was to re-evaluate the current screening policy for Group B Streptococcus (GBS), considering colonization and prevalence rates and costs estimates. This was a retrospective cohort study including term pregnancies between 2015 and 2016 insured by Maccabi Healthcare Services (MHS). A costs estimation model was performed comparing three approaches: universal culture-based screening, current policy in Israel and the current clinical scenario. Out of 54,759 pregnancies, 46.3% women undergo GBS culture-based screening. Overall GBS colonization rates in screened women were 21%. Six EOGBSD cases were identified, all offspring of mothers who were not screened. EOGBSD prevalence rate was 11 per 100,000. Universal culture-based screening was found to be 50% less costly than the current risk-based policy, and would have prevented 20.29 per 100,000 cases. Universal GBS culture-based screening was found to be more cost-effective, compared to the current policy and screening behaviors. Due to the clinical and economic benefits, we recommend that a change in policy should be considered.

Peripheral Venous Catheter-related Bloodstream Infections in Hospitalized Children: The Role of Gram-negative Bacteria.

BACKGROUND: Peripheral venous catheter (PVC) is the most used vascular access device in medicine, allowing administration of intravenous fluids and medications. Known complications associated with PVC include extravasation, phlebitis and rarely bloodstream infection (BSI). Data regarding PVC-related BSI in children are lacking. Our aim was to evaluate the epidemiology, clinical and microbiologic characteristics of pediatric inpatients with PVC-related BSI. METHODS: A retrospective study was conducted in a pediatric tertiary care center. Children with BSI, admitted to general pediatric departments during 2010-2019, were identified and their medical records examined. Patients with BSI and phlebitis were further characterized and included in the analysis. We excluded patients with central venous catheters, other identified source of infection and with BSI upon admission. Data collected included patients' demographics and clinical and microbiologic characteristics. RESULTS: Twenty-seven children with PVC-related BSI were identified and included in the study, consisting of 0.2% of the total BSI cases. Patient's median age was 24 (range, 1.5-213) months, 14/27 (52%) were female and 6 (22%) were previously healthy while 21 (78%) had prior medical conditions. Sixteen (59.3%) patients had Gram-negative BSI and 6 (22.2%) Gram-positive bacteria. Polymicrobial infection occurred in 4 (14.8%) patients and Candida albicans in 1 (3.7%) patient. The most common isolated bacteria were Klebsiella spp and Staphylococcus aureus. Longer dwell-time was a predictor of Gram-negative bacteria. CONCLUSIONS: PVC-related BSI due to Gram-negative bacteria was more common than to Gram-positive bacteria. Clinicians should consider an initial broad-spectrum antibiotic coverage for PVC-related BSI in hospitalized pediatric patients.

Postoperative prognosis of unerupted teeth after removal of supernumerary teeth or odontomas.

INTRODUCTION: Impacted teeth do not always erupt spontaneously after removal of supernumerary teeth or odontomas. The purpose of this study was to examine the effect of several variables on eruption of impacted teeth in children with supernumeraries or odontomas. METHODS: The sample consisted of 53 patients with 69 impacted teeth; the supernumeraries or odontomas were removed without other interventions. The patients were identified retrospectively and followed until the impacted teeth erupted to their correct positions or until orthodontic traction was started. RESULTS: Loss of space, a second surgical procedure, a third surgical procedure, and orthodontic treatment were recorded in 77.6%, 53.8%, 9.4%, and 85% of the patients, respectively. Spontaneous eruption occurred in 83%, 75%, 46%, 19%, and 32% of the impacted teeth with normal and small size superlative, conical, tuberculated, and odontoma forms, respectively. In the univariate analysis, spontaneous eruption correlated with apex distance of the impacted tooth relative to its estimated position (P <.001), extent of vertical impaction (P <.001), obstacle form (P <.019), stage of root development of supernumerary tooth (P = .006), angle of impaction relative to the midline (P = .015), and time of surgery (P = .05). In the multivariate logistic regression analysis, higher distraction of the apex of the impacted tooth relative to its estimated correct position and the obstacle form (tuberculated and odontomas) were independently associated with impediment of spontaneous eruption (P = .03 and P = .04, respectively). CONCLUSIONS: Spontaneous eruption of impacted teeth correlated mostly with lower distraction of the impacted tooth apex and obstacle form (conical and superlative). Immediate orthodontic traction is recommended concomitantly with the first surgery to remove supernumerary teeth.

Influenza vaccination: reduction in hospitalizations and death rates among members of "Maccabi Healthcare Services" during the 2000-2001 influenza season.

BACKGROUND: Upper respiratory tract illnesses have been associated with an increased risk of morbidity and mortality. OBJECTIVE: To assess the influence of vaccination against influenza on the risk of hospitalization in internal medicine and geriatric wards, and the risk of death from all causes during the 2000-2001 influenza season. METHODS: A historical cohort study was conducted using computerized general practitioner records on patients aged 65 years and above, members of "Maccabi Healthcare Services"--the second largest health maintenance organization in Israel with 1.6 million members. The patients were divided into high and low risk groups corresponding to coexisting conditions, and were studied. Administrative and clinical data were used to evaluate outcomes. RESULTS: Of the 84,613 subjects in the cohort 42.8% were immunized. At baseline, vaccinated subjects were sicker and had higher rates of coexisting conditions than unvaccinated subjects. Vaccination against influenza was associated with a 30% reduction in hospitalization rates and 70% in mortality rates in the high risk group. The NNT (number needed to treat) measured to prevent one hospitalization was 53.2 (28.2 in the high risk group and 100.4 in the low risk group). When referring to length of hospitalization, one vaccine was needed to prevent 1 day of hospitalization among the high risk group. Analyses according to age and the presence or absence of major medical conditions at baseline revealed similar findings across all subgroups. CONCLUSIONS: In the elderly, vaccination against influenza is associated with a reduction in both the total risk of hospitalization and in the risk of death from all causes during the influenza season. These findings compel the rationale to increase compliance with recommendations for annual influenza vaccination among the elderly.

Seroepidemiology of hepatitis A antibodies among children's hospital staff.

BACKGROUND: With improved socioeconomic conditions, adults are more frequently seronegative for hepatitis A virus (HAV) and therefore susceptible to infection. A safe and efficacious active HAV vaccine has been developed and licensed. The general recommendation is to vaccinate populations at increased occupational exposure to HAV. AIM: To determine the seroprevalence of HAV antibodies among children's hospital employees and to correlate seropositivity with demographic and occupational variables as a basis for formulating vaccine recommendations. METHODS: The staff of a tertiary pediatric medical center participated by answering a structured questionnaire on demographic and occupational data and by donating venous blood for determining HAV antibodies by an enzyme immunoassay. Univariate and multivariate analyses were conducted to identify variables associated with HAV seropositivity. RESULTS: HAV antibodies were found in 48.3% of the 499 employees studied, being lowest in pediatricians (38.7%), and increased with years of work at the hospital, job percentage and contact with pediatric patients. However, multivariate analysis showed that only the sociodemographic variables (age and crowding during childhood) were independently and significantly associated with seropositivity. CONCLUSIONS: HAV seropositivity was associated mainly with sociodemographic variables. Most children's hospital employees, especially pediatricians and other young (<40 years) employees, are seronegative and therefore susceptible to HAV. Vaccination of the high risk groups should be considered.