Impact of COVID-19 Pandemic on Human Papillomavirus Vaccine Uptake in Israel.

OBJECTIVE: Isolation and school closure during the COVID-19 pandemic could decrease human papillomavirus (HPV) vaccination uptake and potentially increase future HPV-related morbidity among unvaccinated populations. The aim of our study was to investigate HPV vaccination rates in Israel during the pandemic. METHODS: The HPV vaccination rates were compared before and during the COVID-19 pandemic years (2020-2021). Data regarding HPV vaccination between 2015 and 2021 were extracted from the Israeli Ministry of Health online reports. Vaccination rates were compared with other childhood vaccines, given at similar ages. Israeli HPV vaccination rates were further compared with England and Australia, which have an established vaccination infrastructure. RESULTS: The average Israeli coverage of first-dose HPV vaccine was 60.2%, with significant variations from 2015 to 2021. During the pandemic years, first-dose vaccine coverage increased compared with the 3 previous years. The pandemic had also no apparent influence on other childhood vaccine uptake, even though adolescents in Israel missed many school days during this time. Average vaccine uptake in England and Australia was significantly higher than Israel ( p = .009); however, first-dose vaccination rates decreased considerably in England during 2020, to a nadir of 59%. The pandemic had little effect on HPV vaccination rates in Australia. CONCLUSIONS: Despite many school days missed, the COVID-19 pandemic did not result in a decrease in HPV vaccine uptake in Israel. The pandemic could prove a good opportunity to further educate the public regarding the importance of whole-population vaccination programs. Implementing catch-up vaccination programs may bridge "vaccination gaps" that may be caused by future pandemics.

Is there a 'weekend effect' on mortality among hospitalised patients in an internal medicine ward? A retrospective study.

BACKGROUND: Previous studies demonstrated a 'weekend effect' and a 'night effect' of increased mortality among patients admitted during weekends or night shifts, presumably due to understaffing. AIMS: To examine whether death during hospitalisation follows a similar effect regardless of admission time. METHODS: A retrospective cohort study among deceased patients hospitalised in the internal medicine wing of a tertiary medical centre in Israel, between 2019 and 2020. Demographic and medical data were retrieved from electronic medical charts. Causes of death were specifically categorised. We applied statistical models to test for differences in mortality using incidence rate ratio (IRR) according to the day, time and cause of death. RESULTS: One thousand, two hundred and seventy-eight deceased patients were included. All-cause mortality was similar between weekends and weekdays. When sepsis was the cause of death, higher IRR were demonstrated on Fridays in comparison with weekdays (IRR 1.4; 95% confidence interval (CI) 1.1-1.9; P < 0.05). Other causes of death were not consistent with a 'weekend effect'. Mortality during night shifts was higher in comparison with the afternoon (IRR 1.5; 95% CI 1.3-4.7) and similar to the morning (IRR 1; 95% CI 0.9-1.2). CONCLUSION: Our study did not find a pattern of 'weekend effect' or 'night effect' on all-cause mortality among hospitalised patients in internal medicine wards. Our findings suggest that perhaps specifically death from sepsis, and not all-cause mortality, can be used as a surrogate for the measurement of understaffing or quality of care in the internal ward.

Chronic aspirin use and survival following sepsis-A propensity-matched, observational cohort study.

OBJECTIVES: The use of antiplatelet agents is postulated to lead to improved outcomes in sepsis. We aimed to evaluate whether chronic, pre-hospitalization aspirin use leads to improved outcomes in patients with sepsis. METHODS: We conducted an observational cohort study among patients with sepsis, hospitalized in internal medicine wards in a single university-affiliated medical center. A propensity-score model was used to match and compare patients on chronic aspirin use to non-users. Patients with established cardiovascular disease were excluded. The primary outcome was survival rates at 30 days. Secondary outcomes included survival rates at 90 days, days of fever, length of hospital stay, and hospital readmission within 90 days. RESULTS: A total of 1671 patients fulfilled the inclusion criteria. 533 chronic aspirin users were matched to 533 aspirin non-users. Survival rates were significantly higher among patients on chronic aspirin use (hazard ratio (HR) 0.67; 95% CI, 0.51-0.89)). This effect was highlighted in several subgroups of patients, as patients with chronic obstructive pulmonary disease (COPD) or those with chronic use of beta blockers showed the greatest survival benefit with aspirin use. Patients in the aspirin group also showed significantly higher 90 days survival rates (HR 0.69; 95% CI, 0.57-0.92; p = 0.006) and experienced less days of fever in comparison to the control group. DISCUSSION: Pre-hospitalization treatment with aspirin for patients without established cardiovascular disease may be associated with mortality reduction, as shown in this is hypothesis-generating single center observational study.

Mild thrombocytopenia and the risk for postpartum hemorrhage in twin pregnancies.

OBJECTIVE: We aimed to investigate the association of mild thrombocytopenia with postpartum hemorrhage (PPH) and blood transfusion among women with twin gestations. METHODS: A retrospective cohort study (Jan 2015 to May 2019) was performed. Women with twin pregnancies and pre-delivery mild thrombocytopenia were compared to those with normal platelet count. The primary outcome was the rate of PPH, defined as a composite of one or more of the following: (1) need for packed red blood cell transfusion; (2) postpartum hemoglobin decline of ≥3 g/dL; and (3) the use of postpartum uterotonics agents in addition to oxytocin. RESULTS: Of 1085 women who were included in final analysis, 315 (30.9%) had mild thrombocytopenia (and 770 (69.1%) served as controls. The rate of PPH was increased in the study group (14% vs. 9.4%, P = 0.03), as was the use of uterotonic agents (3.8% vs. 1.3%, respectively, P = 0.02). The rate of blood product transfusion and hemoglobin decline >3 g/dL was not significantly different between the groups. In multivariate logistic regression analysis, mild thrombocytopenia was associated with a higher risk for PPH (OR 1.55 [95% CI 1.02-2.35], P = 0.02). CONCLUSION: Mild thrombocytopenia in twin pregnancies is associated with an increased risk of interventions such as the use of uterotonic agents.

Prolonged exposure to meconium in cases of spontaneous premature rupture of membranes at term and pregnancy outcome.

OBJECTIVE: To evaluate the impact of prolonged exposure to meconium-stained amniotic fluid (MSAF), in women with term pre-labor spontaneous rupture of membranes (PROM), on pregnancy outcome. METHODS: A retrospective cohort study of women who gave birth in a single university-affiliated tertiary medical center (2011-2019). Eligibility was limited to singleton pregnancies at term who presented with PROM. Women with MSAF were immediately induced and were compared to low-risk pregnant women with clear amniotic fluid (CAF) at admission who underwent induction of labor 24 h after rupture of membranes. All women were stratified into 4-time frame groups from rupture of membranes to delivery: T0: 0-7 h, T1: 8-13 h, T2: 14-18 h, and T3: > 18 h for the MSAF group. The time frames for the CAF were: T0 - 24-31 h, T1: 32-38 h, T2: 40-44 h, and T3: > 44 h. The maternal adverse composite outcome included any of the following: intrapartum fever (IPF), prolonged second stage (PSS), need for manual removal of suspected retained placenta, postpartum hemorrhage, and readmission within 45 days after delivery. The adverse composite neonatal outcome included one or more of the following: meconium aspiration syndrome, neonatal asphyxia, need for respiratory support, and intracranial hemorrhage. RESULTS: Overall, 1631 women met the inclusion criteria (536 in the MSAF and 1095 in the CAF group). Both groups showed a gradual decrease in the rate of vaginal delivery over time, the vaginal delivery rate in the MSAF group was 75.7% at T0 in comparison to 61.6% at T3 (p < .001). In the CAF group, the vaginal delivery rate was 84.5% at T0 in comparison to 68.8% at T3 (p < .001). This decrease was in concomitance with an increase in the rates of prolonged second-stage and intrapartum fever. There were no significant differences in the rates of postpartum hemorrhage, suspected retained placenta, or readmission within 45 days between women with either MSAF or CAF. There was a significant gradual increase in the adverse composite neonatal outcome in the MSAF group (1.9% at T0, 5.2% at T1, 6.0% at T2, and 8.2% at T3. p = .038). No similar increase was found in the CAF group (2.5% at T0, 4.1% at T1, 2.6% at T2, and 4.1% at T3. p = .449). CONCLUSION: Prolonged rupture of membranes in the presence of meconium does not affect maternal outcomes, however, prolonged exposure to meconium lead to an increased adverse neonatal outcome.

Cefazolin prophylaxis in minimally invasive gynecologic surgery - are dosage and timing appropriate? Prospective study using resampling simulation.

OBJECTIVE: Cefazolin is a widely used antimicrobial prophylactic agent, however the appropriate dosage, timing, pharmacology and microbial coverage have not been well-established for gynecologic procedures. We aimed to describe serum concentrations and pharmacokinetics of Intravenous cefazolin given to women prior to scheduled minimally invasive gynecologic surgeries, and to determine whether appropriate antimicrobial coverage had been achieved in short time from prophylactic administration to surgical start time. METHODS: A prospective cohort analysis study, using a resampled dataset, of women undergoing scheduled gynecological surgeries in a university affiliated tertiary medical center. IV cefazolin (1 or 2 gr) was administered prior to incision to women weighing <80 kg (Group A) and ≥80 kg (Group B), respectively. Cefazolin serum levels were obtained at the time of skin incision (Time 0) and 30 min later (Time 30), measured by high-pressure liquid chromatography (HPLC). Appropriate antimicrobial coverage was defined when cefazolin serum levels were above minimal inhibitory concentrations (MIC) for Enterobacteriaceae. RESULTS: Overall, 21 women were included. The mean time interval between drug administration and incision did not differ between the two groups (18 ± 10 min vs. 11 ± 10 min, respectively, p = .0.25). A hierarchical mixed linear regression model, using a simulation of multiple random bootstrap resampling (n = 1,000), revealed that cefazolin serum levels exceeded MIC, regardless of the timing of administration in the sampling intervals. Mean cefazolin serum levels in time 0 and time 30 min were not affected by BMI in patients receiving 1 gr. CONCLUSION: A single dose of IV cefazolin given shortly prior to skin incision provides serum concentrations above minimal inhibitory concentrations for susceptible pathogens in most women undergoing scheduled minimally invasive gynecologic surgery.

Mild thrombocytopenia prior to elective cesarean section is an independent risk factor for blood transfusion.

PURPOSE: Thrombocytopenia is the second most common hematological disorder in pregnancy and complicates approximately 10% of all pregnancies. The data regarding the association of mild thrombocytopenia in women undergoing cesarean section and risk of bleeding or bleeding-related complications are scarce. Thus, the aim of the current study was to assess the association of mild thrombocytopenia with hemorrhage-related morbidities, among patients undergoing elective cesarean section. METHODS: We performed a retrospective cohort study, in a single tertiary university-affiliated medical center, between 1 January 2012 and 31 May 2019. Medical charts of women who underwent elective cesarean section at term (37+0/7-41 + 6/7 weeks of gestations) were retrieved and analyzed. We compared women with mild thrombocytopenia (platelet count of 100-149 × 103/µL) to women with normal platelet count (150-450 × 103/µL). The primary outcome was the need for red blood cell transfusion during the index admission. A secondary outcome was severe bleeding not requiring blood transfusion defined as postpartum hemoglobin decline of ≥ 3 g/dL as compared to the prepartum levels. RESULTS: During the study period, 1577 women were included in the final analysis, of them 396 (25.11%) had mild thrombocytopenia prior to delivery. As compared to the control group, women with mild thrombocytopenia had higher rates of blood transfusion (3.79 vs. 1.52%, p = 0.01), and had a significant decline in hemoglobin levels. In a multivariable logistic regression model, mild thrombocytopenia was independently associated with blood transfusion with adjusted OR of 2.34 (95% CI 1.10-4.96, p = 0.03). CONCLUSION: Preoperative mild thrombocytopenia is associated with an increased risk of blood loss and blood transfusion in women undergoing elective CS. More studies are required to assess those observations in context of urgent cesarean sections and whether any preventive measures can reduce the risk for bleeding.

Pregnancy outcomes in women with inflammatory bowel disease who successfully conceived via assisted reproduction technique.

OBJECTIVE: Women with inflammatory bowel disease (IBD) have an increased risk for adverse pregnancy outcome, so as women using assisted reproduction technology (ART). However, data are scarce regarding the risk imposed by the combination of both. Thus, we aimed to assess pregnancy outcome in these women. METHODS: A retrospective case-control study, of women with IBD who conceived using ART due to female infertility. The study group (IBD-ART) was matched using propensity score and compared in a 1:1 ratio with three control groups, IBD patients who conceived spontaneously (IBD-SP), women using ART (H-ART) and women who conceived spontaneously (H-SP). RESULTS: The study group comprised of 49 women with IBD conceived via ART that gave birth at our center during the study period. All studied groups did not differ in demographics and obstetric characteristics. IBD groups (both ART and spontaneous) were comparable in disease status prior and throughout pregnancy. Maternal outcome showed no difference regarding preterm birth and pregnancy complications among all studied groups. Women in the IBD-ART group had decreased rates of vaginal delivery (34.7% vs 57.1%, p = 0.032) and higher rates of elective CS (32.7% vs 14.3%, p = 0.048) in comparison to H-SP group, but comparable rates to both IBD-SP and H-ART groups. Neonatal outcomes were comparable among all studied groups. In a sub-analysis by disease type, a higher rate of gestational diabetes was found among ulcerative colitis patients using ART (29.4% Crohn's vs 6.1% UC, p = 0.025). CONCLUSION: Patients with IBD undergoing ART have comparable pregnancy outcome to women using ART and to patients with IBD with spontaneous pregnancy.

Perinatal outcomes of African refugees after their integration into the Israeli health care system.

OBJECTIVE: Evaluate whether the incorporation of the refugees into the Israeli medical system resulted in improvements in perinatal outcomes, namely a reduction in the number of preterm deliveries and a decrease in NICU admissions. METHODS: Retrospective cohort study. Electronic medical records of all African immigrants who delivered in our tertiary referral center between January 2018 and September 2019 were reviewed. African patients' demographics, maternal and perinatal outcomes were compared to those of native Israeli population. In addition, the results were compared to the cohort from our previous study from 2010. RESULTS: A total of 20,796 deliveries took place at our labor and delivery department during the study period. Of these, 3% of all deliveries were of African refugees. Total rates of preterm deliveries <37 weeks was similar between groups, while rate of premature deliveries <34 week was higher among refugees. Rates of extreme prematurity <28 weeks were also similar between groups. Rate of meconium stained amniotic fluid, neonatal weight <2000 g as well as NICU admissions were significantly higher among refugees. CONCLUSION: Though perinatal results have not substantially improved with the incorporation of a refugee population into a healthcare system, some progression has indeed been achieved in some perinatal parameters.

Outcomes of ultrasound and physical-exam based cerclage: assessment of risk factors and the role of adjunctive progesterone in preventing preterm birth-a retrospective cohort study.

OBJECTIVE: To assess outcomes of ultrasound and physical examination-based cerclage performed at mid to late second trimester and to assess the potential added value of progesterone treatment combined with cerclage for preventing preterm birth. STUDY DESIGN: A retrospective cohort study of women who underwent cerclage in a university-affiliated tertiary medical center (2012-2018). Inclusion criteria included only ultrasound-based cerclage and physical examination-based cerclage. Women who underwent history-based cerclage or multiple gestations were excluded. Study groups were stratified by previous PTB < 37 weeks and other risk factors for PTB. Primary outcome was the incidence of preterm birth < 35 weeks of gestation. Secondary outcomes included the potential added value of progesterone treatment and neonatal outcome. RESULTS: Sixty-nine women underwent cervical cerclage placement between 16-23 weeks of gestation. All women had short cervix (cervical length of < 25 mm) at presentation. Indications for cerclage placement included: 29% previous PTB, 32% prior cervical interventions (history of at least one D&C, hysteroscopy or cold-knife conization in the past), 22% had cervical dilatation > 1 cm at presentation, 12% due to failure of progesterone treatment defined as continued cervical shortening after 14 days of progesterone treatment, and 5% had other indications. Overall, 42 women (61%) gave birth at term. 27 women (39%) delivered prior to 37 weeks of gestation, of them, 20 women (29%) gave birth prior to 35 weeks. Overall median gestational age at delivery was 35 + 5 ± 4.7 weeks. Cervical dilatation at presentation of > 1 cm was associated with an increased risk for PTB < 35 weeks (OR 3.57, CI 1.43-30.81, p = 0.036). Previous PTB, prior cervical interventions and extent of cervical shortening at presentation did not increase the risk of PTB. Progesterone treatment in addition to cerclage did not result in a decreased risk for PTB < 35 weeks of gestation (OR 2.83, CI 0.58-13.89, p = 0.199). CONCLUSION: Late second trimester cerclage is a practical measure for preventing PTB in cases of asymptomatic cervical shortening. Our study did not find adjunctive benefit for progesterone treatment with physical or ultrasound-based cerclage in reducing the rate PTB.

Paleolithic diet during pregnancy-A potential beneficial effect on metabolic indices and birth weight.

BACKGROUND: Paleolithic diet has recently gained popularity due to its presumed health benefits. The favorable metabolic effects of this diet were assessed in non-pregnant population but its impact during pregnancy remains to be evaluated. STUDY DESIGN: A retrospective cohort study comparing two groups. Group A comprised of women with singleton low-risk pregnancy adherent to paleolithic diet throughout gestation (n = 37). Group B comprised low risk pregnant women on a regular diet (n = 39). Women were excluded if they had low adherence to diet, started paleolithic diet during pregnancy, and had pre-gestational diabetes mellitus or other types of metabolic syndrome such as pre gestational hyperlipidemia, hypertension or BMI > 35. Blood indices such as Glucose challenge test scores, hemoglobin, ferritin, and TSH levels were compared. Other pregnancy factors such as maternal weight gain, rest days during gestation and pregnancy complications such as IUGR, GDM or preeclampsia were compared. Lastly, obstetrical outcomes such as mode of delivery and complications such as high-grade tears, as well as neonatal factors such as birth weight and pH were compared between the two groups. RESULTS: General maternal characteristics such as age, BMI and parity were comparable between the two groups. Women who maintained a paleolithic diet had a significant decrease in glucose challenge test scores (95.8 mg/dL vs. 123.1 mg/dL, p < 0.01) and increase in hemoglobin levels (12.1 g/dL vs. 11.05 g/dL p < 0.01) and Ferritin (32.1 vs 21.3 mg/mL, p = 0.03) compared to women maintaining regular diet. Maternal pregnancy weight gain was also slightly decreased in group A (9.3Kg vs. 10.8 kg, p = 0.03). Birthweights were lower in group A (3098 g Vs.3275 g, p = 0.046) with no difference in adverse neonatal outcomes. We found no differences in other pregnancy complications or labor outcomes such as mode of delivery, shoulder dystocia or high grade perineal tears. CONCLUSION: Paleolithic diet maintained during pregnancy may have a beneficial effect on the glucose tolerance. It also may increase iron stores and hemoglobin levels. Neonates of women maintaining paleolithic diet are slightly lighter but appropriate for gestational age with no difference in neonatal outcomes.

[CHRONIC MYELOID LEUKEMIA IN A YOUNG MALE PRESENTING WITH BILATERAL CALF PAIN DUE TO LEUKOSTASIS].

Chronic myeloid Leukemia (CML) is a chronic myeloproliferative disorder, caused by the unregulated proliferation of granulocytes at different stages of development and maturation. Leukostasis is one of the complications of CML, causing partial or total occlusion of microvasculature with a variety of clinical manifestations, mostly ophthalmic, neurologic or respiratory. Recently, we encountered a 21-year old soldier, who complained of severe bilateral calf pain which began a few months earlier during training. He underwent complete ambulatory orthopedic evaluation which was unrevealing, and finally presented to the hospital casualty department where CML was diagnosed on the basis of an elevated WBC count and morphologic findings. Bilateral retinal hemorrhages due to leukostasis were noticed at fundoscopy. The calf pain resolved completely after leukapheresis and initial cytoreductive therapy and was in retrospect attributed to peripheral leukostasis. To the best of our knowledge this is the first report of CML presenting with bilateral calf pain due to Leukocytosis and possible leukostasis. This case report highlights the importance of differential diagnosis in cases of calf pain and the awareness of this rare manifestation of CML.

Fertility in women after surgical treatment of nonepithelial ovarian tumors.

Conservative treatment is an acceptable option for women with nonepithelial ovarian tumors who wish to preserve fertility.