Hadassah Medical Center
  • Jerusalem, Israel
Recent publications
Background In most countries, including those with national health insurance or comprehensive public insurance, some expenses for cancer treatment are borne by the ill and their families. Objectives This study aims to identify the areas of out-of-pocket (OOP) spending in the last half-year of the lives of cancer patients and examine the extent of that spending; to examine the probability of OOP spending according to patients’ characteristics; and to examine the financial burden on patients’ families. Methods 491 first-degree relatives of cancer patients (average age: 70) who died 3–6 months before the study were interviewed by telephone. They were asked about their OOP payments during the last-half year of the patient's life, the nature of each payment, and whether it had imposed a financial burden on them. A logistic regression and ordered logit models were used to estimate the probability of OOP expenditure and the probability of financial burden, respectively. Results Some 84% of cancer patients and their relatives incurred OOP expenses during the last half-year of the patient’s life. The average levels of expenditure were US$5800on medicines, $8000 on private caregivers, and $2800 on private nurses. The probability of paying OOP for medication was significantly higher among patients who were unable to remain alone at home and those who were less able to make ends meet. The probability of spending OOP on a private caregiver or private nurse was significantly higher among those who were incapacitated, unable to remain alone, had neither medical nor nursing-care insurance, and were older. The probability of a financial burden due to OOP was higher among those unable to remain alone, the incapacitated, and those without insurance, and lower among those with above-average income, those with better education, and patients who died at home. Conclusions The study yields three main insights. First, it is crucial that oncology services provide cancer patients with detailed information about their entitlements and refer them to the National Insurance Institute so that they can exercise those rights. Second, oncologists should relate to the financial burden associated with OOP care at end of life. Finally, it is important to sustain the annual increase in budgeting for technologies and pharmaceuticals in Israel and to allocate a significant proportion of those funds to the addition new cancer treatments to the benefits package; this can alleviate the financial burden on patients who need such treatments and their families.
Juvenile polyposis syndrome (JPS), has diverse phenotypes. Aim: To assess mutation rate, clinical features and genotype-phenotype correlation among Israeli JPS kindreds from different ethnicities. Methods Patients’ data were extracted retrospectively from 5 centers. Results Thirty five kindreds (49 patients) were included. Thirty one (89%) Jewish [10 (32%) Ashkenazi; 9 (29%) Sephardi; 11 (35%) non-Russia former Soviet-Union countries (NRFSU), one (3%) unknown]. 40/49 individuals from 27 families underwent genetic testing. Among them 34, from 21 families (85, 78%, respectively) had a pathogenic mutation: BMPR1A n = 15 (71%), SMAD4 n = 6 families (29%). While no SMAD4 mutation was described among Jewish families from NRFSU, 7 NRFSU families carried a founder mutation comprising a large genomic deletion of BMPR1A . GI involvement was reported in 42 patients (86%): colonic polyps ( n = 40, 95%, > 50 polyps n = 14, 35%) and 12 underwent colonic resection. Fourteen patients (34%) had gastric or small bowel involvement ( n = 5) and 4\14 underwent gastrectomy due to polyp burden. Families from NRFSU had more gastric involvement (66.7% vs. 22.2%- Sephardic and 20%- Ashkenazi Jews; p = 0.038), with more gastric polyps ( p = 0.017). Conclusions We demonstrated a high rate of mutation detection in the heterogeneous population of Israel. Patients from NRFSU with BMPR1A mutation had high rate of gastric involvement.
Background Treatment of Diffuse Large B Cell Lymphoma (DLBCL) patients with rituximab and the CHOP treatment regimen is associated with frequent intrinsic and acquired resistance. However, treatment with a CD47 monoclonal antibody in combination with rituximab yielded high objective response rates in patients with relapsed/refractory DLBCL in a phase I trial. Here, we report on a new bispecific and fully human fusion protein comprising the extracellular domains of SIRPα and 4-1BBL, termed DSP107, for the treatment of DLBCL. DSP107 blocks the CD47:SIRPα ‘don’t eat me’ signaling axis on phagocytes and promotes innate anticancer immunity. At the same time, CD47-specific binding of DSP107 enables activation of the costimulatory receptor 4-1BB on activated T cells, thereby, augmenting anticancer T cell immunity. Methods Using macrophages, polymorphonuclear neutrophils (PMNs), and T cells of healthy donors and DLBCL patients, DSP107-mediated reactivation of immune cells against B cell lymphoma cell lines and primary patient-derived blasts was studied with phagocytosis assays, T cell activation and cytotoxicity assays. DSP107 anticancer activity was further evaluated in a DLBCL xenograft mouse model and safety was evaluated in cynomolgus monkey. Results Treatment with DSP107 alone or in combination with rituximab significantly increased macrophage- and PMN-mediated phagocytosis and trogocytosis, respectively, of DLBCL cell lines and primary patient-derived blasts. Further, prolonged treatment of in vitro macrophage/cancer cell co-cultures with DSP107 and rituximab decreased cancer cell number by up to 85%. DSP107 treatment activated 4-1BB-mediated costimulatory signaling by HT1080.4-1BB reporter cells, which was strictly dependent on the SIRPα-mediated binding of DSP107 to CD47. In mixed cultures with CD47-expressing cancer cells, DSP107 augmented T cell cytotoxicity in vitro in an effector-to-target ratio-dependent manner. In mice with established SUDHL6 xenografts, the treatment with human PBMCs and DSP107 strongly reduced tumor size compared to treatment with PBMCs alone and increased the number of tumor-infiltrated T cells. Finally, DSP107 had an excellent safety profile in cynomolgus monkeys. Conclusions DSP107 effectively (re)activated innate and adaptive anticancer immune responses and may be of therapeutic use alone and in combination with rituximab for the treatment of DLBCL patients.
Background Noninvasive ventilation (NIV) is a promising alternative to invasive mechanical ventilation (IMV) with a particular importance amidst the shortage of intensive care unit (ICU) beds during the COVID-19 pandemic. We aimed to evaluate the use of NIV in Europe and factors associated with outcomes of patients treated with NIV. Methods This is a substudy of COVIP study—an international prospective observational study enrolling patients aged ≥ 70 years with confirmed COVID-19 treated in ICU. We enrolled patients in 156 ICUs across 15 European countries between March 2020 and April 2021.The primary endpoint was 30-day mortality. Results Cohort included 3074 patients, most of whom were male (2197/3074, 71.4%) at the mean age of 75.7 years (SD 4.6). NIV frequency was 25.7% and varied from 1.1 to 62.0% between participating countries. Primary NIV failure, defined as need for endotracheal intubation or death within 30 days since ICU admission, occurred in 470/629 (74.7%) of patients. Factors associated with increased NIV failure risk were higher Sequential Organ Failure Assessment (SOFA) score (OR 3.73, 95% CI 2.36–5.90) and Clinical Frailty Scale (CFS) on admission (OR 1.46, 95% CI 1.06–2.00). Patients initially treated with NIV (n = 630) lived for 1.36 fewer days (95% CI − 2.27 to − 0.46 days) compared to primary IMV group (n = 1876). Conclusions Frequency of NIV use varies across European countries. Higher severity of illness and more severe frailty were associated with a risk of NIV failure among critically ill older adults with COVID-19. Primary IMV was associated with better outcomes than primary NIV. Clinical Trial Registration NCT04321265 , registered 19 March 2020, https://clinicaltrials.gov .
PurposeAuditory feedback (AF) contributes to speech intelligibility (SI) which is vital in social interactions to examine AF effect on SI of adults with cochlear implant (CI). The relationship between age of CI implantation and AF on SI was examined as well.Method Twenty native Hebrew speaker pre-lingual adults with a hearing loss using CIs from ages 2 to 19 years. Participants were recorded reading excerpts from a book and word lists from MIDBAR test in two situations—with and without using their CIs. Sixteen judges listened to the recordings and rated the speech characteristics of the participants reading the excerpts using an adapted version of Speech Intelligibility Test and Intelligibility Questionnaire for Teachers.ResultsSignificant differences were found between the SI of words of those who received CI before and after 3 years. AF effect was found only for the older implantation group. The questionnaire indicates good reliability among all the speech characteristics. The speech characteristics most affected by the AF are the disruption of consonants followed by the varied degrees of intonation precision and nasality.ConclusionsAF affects speech characteristics differently and is vital to SI. The use of the adapted version of Speech Intelligibility Test and Intelligibility Questionnaire for Teachers can be used clinically to assess SI and rehabilitation of young adults with CI. AF accessed at a younger age decreases the dependency on AF in later years.
Importance Cancer patients have an increased risk of severe disease and mortality from COVID-19, as the disease and antineoplastic therapy cause reduced vaccine immunogenicity. Booster doses have been proposed to enhance protection, and efficacy data are emerging from several studies. Objective To evaluate the proportion of COVID-19 primary vaccination non-responders with cancer who seroconvert after a booster dose. Methods PubMed, EMBASE, CENTRAL, and medRxiv were searched from 1 January 2021 to 10 March 2022. Quality was assessed using the Joanna Briggs Institute Critical Appraisal checklist. Results After eligibility assessment, 22 studies were included in this systematic review and 17 for meta-analysis of seroconversion in non-responders, pooling a total of 849 haematological cancer and 82 solid cancer patients. Haematological cancer non-responders exhibited lower seroconversion at 44% (95% CI 36-53%) than solid cancer at 80% (95% CI 69-87%). Individual patient data meta-analysis found the odds of having a meaningful rise in antibody titres to be significantly associated with increased duration between the second and third dose (OR 1.02, 95% CI 1.00-1.03, P≤ 0.05), age of patient (OR 0.960, 95% CI 0.934-0.987, P≤ 0.05) and cancer type. With haematological cancer patients as a reference, lung cancer patients had 16.8 times the odds of achieving a meaningful increase in antibody titres (OR 16.8, 95% CI 2.95-318, P≤ 0.05) and gastrointestinal cancer patients had 25.4 times the odds of achieving a meaningful increase in antibody titres (OR 25.4, 95% CI 5.26-492.21, P≤ 0.05). Conclusions Administration of a COVID-19 vaccine booster dose is effective in improving seroconversion and antibody levels. Haematological cancer patients consistently demonstrate poorer response to booster vaccines than solid cancer patients.
Bi‐allelic variants in COLEC11 and MASP1 have been associated with 3MC syndrome, a clinical entity made of up four rare autosomal recessive disorders: Carnevale, Mingarelli, Malpuech, and Michels syndromes, characterized by variable expression of facial dysmorphia, cleft lip/palate, postnatal growth deficiency, hearing loss, cognitive impairment, craniosynostosis, radioulnar synostosis, and genital and vesicorenal anomalies. More recently, bi‐allelic variants in COLEC10 have been described to be associated with 3MC syndrome. Syndromic features seen in 3MC syndrome are thought to be due to disruption of the chemoattractant properties that influence neural crest cell migration. We identified nine individuals from five families of Ashkenazi Jewish descent with homozygosity of the c.311G > T (p.Gly104Val) variant in COLEC10 and phenotype consistent with 3MC syndrome. Carrier frequency was calculated among 52,278 individuals of Jewish descent. Testing revealed 400 carriers out of 39,750 individuals of Ashkenazi Jewish descent, giving a carrier frequency of 1 in 99 or 1.01%. Molecular protein modeling suggested that the p.Gly104Val substitution alters local conformation. The c.311G > T (p.Gly104Val) variant likely represents a founder variant, and homozygosity is associated with features of 3MC syndrome. 3MC syndrome should be in the differential diagnosis for individuals with short stature, radioulnar synostosis, cleft lip and cleft palate.
Background: Gallstone disease is common worldwide and can lead to severe complications, including cholangitis; thus, it is important to identify modifiable risk factors for cholangitis. Proton pump inhibitors (PPIs) are commonly prescribed to treat gastroenterological disorders. We aimed to explore whether PPI use is associated with an increased risk of acute cholangitis in patients with gallstone disease. Methods: This retrospective multicenter study included all patients arriving to the hospital over a 10-year period with various presentations of choledocholithiasis. We compared active PPI use in two groups: those with cholangitis (group A) vs. without cholangitis (group B). Results: Overall, 811 patients were included, 161 in group A and 650 in group B. The average age ± standard deviation (SD) in groups A and B was 74.5 ± 20.6 vs. 61.6 ± 20.9 years, respectively. PPI use in group A was higher vs. group B (42.9% vs. 29.1%, p = 0.001). On univariate analysis, male gender (OR 1.47, 95% confidence interval (CI) 1.04-2.08), age (OR 1.04, 95% CI 1.03-1.05), ischemic heart disease (IHD) (OR 1.68, 95% CI 1.07-2.64), hyperlipidemia (OR 1.59, 95% CI 1.11-2.29), hypertension (OR 1.81, 95% CI 1.28-2.57) and PPI use (OR 1.83, 95% CI 1.28-2.61), all were associated with acute cholangitis. On multivariate analysis, only PPI use kept its association after adjustment for age (OR 1.64, 95% CI 1.2-3.7). Conclusions: Active PPI use was associated with a higher rate of cholangitis among patients with choledocholithiasis. We advocate considering this risk before prescribing PPIs to patients with gallstones. Trial registration number: NHR-0263-20 received on 14/01/2021 date 'retrospectively registered'.
Background Psychosocial issues are an integral part of children's health and well-being, and it is widely acknowledged that pediatricians should be involved in their management. We examined the current perception of the pediatrician’s role in the management of psychosocial problems in Israel from the perspective of parents and pediatricians, and identified possible barriers. Methods We assessed parents' and pediatricians' perspectives through a cross sectional survey. 1000 parents with children under 10 were randomly selected from a large database representing the Israeli population and phone-surveyed by a polling company. Due to a low response-rate (5.4%), there was an overrepresentation of married parents and underrepresentation of parents with primary or secondary education. 173 Pediatricians were recruited both at a medical conference and by a web-based questionnaire. Results 55% of the parents reported they were concerned with at least one psychosocial problem, yet less than 50% of them discussed these issues with the pediatrician. 59.9% of the parents did not perceive psychosocial problems as relevant to the pediatrician's role. Pediatricians with some previous training related to psychosocial issues were more likely to report on a lack of professional confidence ( p = .037) and insufficient available resources ( p = .022) as barriers to their involvement, while pediatricians who had no training were more likely to report on the parents' perception of their role as the barrier to involvement ( p = .035). Conclusions Parents tend to avoid the discussion of psychosocial concerns in pediatric settings due to their perception that it's irrelevant to the pediatrician's role. Trained pediatricians feel unconfident in their ability to manage psychosocial issues and report on a lack of suitable resources. These findings suggest current pediatric mental-health training is insufficient to equip pediatricians with the knowledge and skills required to their involvement in psychosocial problems, and imply necessary changes to environment of community-based pediatrics. In order to change the practice of pediatricians in the community to enable them to address a variety of psychological issues, appropriate training is needed, through all stages of the pediatrician’s professional life, including medical school, pediatric residency and continuous medical education.
Purpose To determine the factors associated with successful trial of labor after cesarean (TOLAC) among grand-multiparous (GMP) women. Methods A retrospective cohort study was conducted, including all GMP women (≥ 5 deliveries) undergoing TOLAC during 3/2011 and 6/2020, delivering a singleton cephalic newborn. Factors associated with successful vaginal delivery were examined by multivariable analysis. Results Overall, 381/413 (92.2%) GMP succeeded TOLAC. Maternal characteristics did not differ between TOLAC success and TOLAC failure groups. Previous cesarean delivery characteristics did not differ between study groups. The median number of previous vaginal births after cesarean was 2 [interquartile range 1–4]. Gestational age at TOLAC was lower in the success group (mean 371/7 ± 36/7 vs. 385/7 ± 31/7 weeks, p = 0.028). A lower rate of modified Bishop score < 4 was associated with TOLAC success [149 (39.1%) vs. 22 (69%), odds ratio (OR) 95% confidence interval (CI) 0.29 (0.13–0.64), p = 0.001]. The rate of induction of labor was higher in the TOLAC failure group [120 (31.5%) vs. 17 (53%), OR 95% CI 0.40 (0.19–0.83), p = 0.013]. The rate of oxytocin administration was higher in the TOLAC failure group [94 (24.7%) vs. 15 (47%) OR (95% CI) 0.37 (0.17–0.77), p = 0.006]. The duration of rupture of membranes was negatively associated with TOLAC success. Neonatal and maternal adverse outcomes did not differ between study groups. In multivariable logistic regression analysis, only the duration of rupture of membranes and modified Bishop score < 4 were independently associated with TOLAC success [adjusted OR (95% CI) 0.98 (0.96–0.99), p = 0.027 and 0.40 (0.16–0.97), p = 0.044]. Conclusion TOLAC among GMP has a very-high success rate. Shortening the duration of ruptured membranes is a modifiable factor that may be associated with increased TOLAC success rates.
Key message Spontaneous labor onset, epidural anesthesia and prior cesarean for non-arrest disorders are strong predictors of successful vaginal birth after cesarean in women delivering a macrosomic fetus. PurposeLower rates of successful vaginal birth after cesarean in association with increasing birthweight were previously reported. We aimed to determine the factors associated with successful trial of labor after cesarean (TOLAC) among primiparous women with fetal macrosomia.MethodsA retrospective cohort study conducted during 2005–2019 at two university hospitals, including all primiparous women delivering a singleton fetus weighing ≥ 4000 g, after cesarean delivery at their first delivery. A multivariate analysis was performed to evaluate the characteristics associated with TOLAC success (primary outcome).ResultsOf 551 primiparous women who met the inclusion criteria, 50.1% (n = 276) attempted a TOLAC and 174 (63.0%) successfully delivered vaginally. In a multivariate analysis, spontaneous onset of labor (aOR [95% CI] 3.68 (2.05, 6.61), P < 0.001), epidural anesthesia (aOR [95% CI] 2.38 (1.35, 4.20), P = 0.003) and history of cesarean delivery due to non-arrest disorder (aOR [95% CI] 2.25 (1.32, 3.85), P = 0.003) were the only independent factors associated with TOLAC success. Successful TOLAC was achieved in 82.0% (82/100) in the presence of all three favorable factors, 61.3% (65/106) in the presence of two factors and 38.6% (27/70) in the presence of one or less of these three factors (P < 0.001).Conclusion Spontaneous onset of labor, epidural anesthesia and prior cesarean delivery due to non-arrest disorders were independently associated with higher vaginal birth after cesarean rate among women with fetal macrosomia, with an overall favorable success rate in the presence of these factors. These findings should be implemented in patient counseling in those contemplating a vaginal birth in this setting.
Rational People with cystic fibrosis carrying residual function (RF) mutations are considered to have a mild disease course. This may influence caregivers and patients on how intensive the treatments should be. Objectives Characterize disease severity of patients carrying RF mutations, using the European CF Society Patient Registry (ECFSPR) data. Methods Demographic, clinical characteristics, lung function and death probability of patients carrying at least one RF mutation were analyzed and compared to patients homozygous to minimal function mutations (MF). Main results Of the 44,594 eligible patients (median age 19.5 years, IQR 10–29.8), 6,636 (14.6%) carried RF mutations, and 37,958 (85.1%) MF mutations. Patients carrying RF mutations were older, diagnosed at a later age, had lower sweat chloride at diagnosis and better FEV1pp at each age group. However, their FEV1pp declined with age and rates of chronic Pseudomonas aeruginosa increased with age. A significant number of patients with RF had FEV1pp similar to patients with MF at each age group. 4.5% of RF patients were treated with oxygen and 2.61% had a lung transplant. With increasing age, 26.6% of RF patients were treated with pancreatic enzymes associated with a more severe lung disease. RF patients had shortened life spans, with mortality starting around the age of 20 years. Conclusions Patients carrying an RF mutations experience a decline of pulmonary function with age, leading to life-shortening. Standard of care therapies and augmenting CFTR function may improve their survival and quality of life.
The purpose of this study was to assess the feasibility of use of a novel uterine fibroid treatment device hypothesized to cause fibroid infarction by increasing intra-tumoral pressure. Between August 2019 and January 2020, 21 uterine fibroids were treated in 16 symptomatic pre-menopausal black women. Pelvic magnetic resonance imaging was performed before the procedure, a day after the procedure and at 1, 3, 6, and 12 months. The subjects were also followed for clinical outcomes and quality of life up to 12 months at a single investigational site. At 3 months, the mean reduction in the fibroid volume was 36.3% (P = .002). Incremental reduction in volume peaked at the end of the follow-up, at the 12-month mark (60.4%; P = .008). There were no procedures in which the users failed to perform laparoscopic pressure suturing of fibroids with the pressure-induced fibroid ischemia device. Improvement in the quality of life was evident in the Health-Related Quality of Life total, Energy/Mood, Control, and Sexual Function domains of the Uterine Fibroid Symptom and Quality of Life questionnaire at 3 months post-procedure. Unanticipated risks were not identified. Serious adverse events were not identified. The initial clinical assessment of the pressure-induced fibroid ischemia device supports feasibility of the approach and does not reveal serious safety concerns. Trial is currently being registered retrospectively (This was a feasibility study and therefore registration was not mandatory).
What is the difference regarding pelvic floor muscle training (PFMT) between women with and without UI, employed at a medical centre? There is a dearth of literature comparing PFMT between women with or without UI in the general population and none, specifically, for women employed at a medical centre. Urinary incontinence (UI) is a common problem for all ages, including females employed at medical centres. PFMT is the first‐line intervention recommended for women with UI. The study aimed to compare women with and without UI employed at a medical centre, regarding knowledge, source of knowledge and practices of PFMT. This was a cross‐sectional comparative study, with a convenience sample of 323 women who were employed at a medical centre, aged 20–50 years old. Two validated questionnaires were used: The International Consultation on Incontinence Questionnaire‐Short Form (ICIQ‐SF) and a new questionnaire, developed for this study, entitled the PFMT Patient reported Outcome Measures (PFMT‐P). Ethical approval was granted with questionnaire completion and implied consent. Data was analysed by SPSS version 22, including descriptive statistics, independent t‐test and Mann–Whitney. From the 323 participants, 56 (17.3%) had UI (UI group—UIG), 221 (68. 4%) were without UI (continence group—CG), and 46 (14.2%) did not answer the ICIQ‐SF. Most of the participants were nurses (208 [66.5%]). There was a high level of knowledge for both groups without a significant difference between the groups. Regarding knowledge about recommended PFMT frequency, 37 (68.5%) in the UIG knew the correct answer compared to 108 (52.2%) in the CG, p = 0.03. The most common information source for all participants was the internet (79 [28.9%]). Most of the participants did not receive information from nurses, doctors and physiotherapists during their post‐partum period. For both groups, lower scores were found for PFMT practice, 9.9 [6.4] in the UIG, 7.8 [4.10] in the CG, (with a maximum score of 35), p = 0.02. Two hundred and ninety‐five (91%) participants reported that they are not currently practicing PFMT, and of them, 46 (15.6%) would like to learn PFMT. Knowledge and exposure to a source of knowledge regarding PMFT were not translated into actual technique practice. Women with UI practice PFMT more frequently than women without UI. A limitation of the study was that it was cross‐sectional with a convenience sample of women employees with the majority being nurses. This may also have affected the knowledge component, as PFMT is studied in nursing school. Future studies can assess the difference between women with and without UI regarding PFMT who are employed in other work settings, as well as in the general population.
External accreditation reviews of undergraduate medical curricula play an important role in their quality assurance. However, these reviews occur only at 4–10-year intervals and are not optimal for the immediate identification of problems related to teaching. Therefore, the Standards of Medical Education in Israel require medical schools to engage in continuous, ongoing monitoring of their teaching programs for compliance with accreditation standards. In this paper, we propose the following: (1) this monitoring be assigned to independent medical education units (MEUs), rather than to an infrastructure of the dean’s office, and such MEUs to be part of the school governance and draw their authority from university institu¬tions; and (2) the differences in the importance of the accreditation standards be addressed by discerning between the “most important” standards that have been shown to improve student well-being and/or patient health outcomes; “important” standards associated with student learning and/or performance; “possibly important” standards with face validity or conflicting evidence for validity; and “least important” standards that may lead to undesirable consequences. According to this proposal, MEUs will evolve into entities dedicated to ongoing monitoring of the education program for compliance with accreditation standards, with an authority to implement interventions. Hopefully, this will provide MEUs and faculty with the common purpose of meeting accreditation requirements, and an agreed-upon prioritization of accreditation standards will improve their communication and recommendations to faculty.
Aims To investigate the impact of patiromer on serum potassium level and its ability to enable specified target doses of renin-angiotensin-aldosterone system inhibitor (RAASi) use in patients with heart failure and reduced ejection fraction (HFrEF). Methods and results A total of 1642 patients with HFrEF and current or a history of RAASi-related hyperkalemia were screened and 1195 were enrolled in the run-in phase with patiromer and optimization of RAASi therapy (≥50% recommended dose of angiotensin-converting-enzyme inhibitor/angiotensin receptor blocker/angiotensin receptor-neprilysin inhibitor, and 50 mg of mineralocorticoid receptor antagonist [MRA] spironolactone or eplerenone). Specified target doses of RAASi therapy were achieved in 878 (84.6%) patients; 439 were randomized to patiromer and 439 to placebo. All patients, physicians, and outcome assessors were blinded to treatment assignment. The primary endpoint was between-group difference in adjusted mean change in serum potassium. Five hierarchical secondary endpoints were assessed. At the end of treatment, the median (interquartile range) duration of follow-up was 27 (13, 43) weeks, the adjusted mean change in potassium was +0.03 mmol/L in the patiromer group and +0.13 mmol/L in the placebo group (difference in adjusted mean change between patiromer and placebo: -0.10 [95% confidence interval, CI -0.13, -0.07] mmol/L, P<0.001). Risk of hyperkalemia >5.5 mmol/L (hazard ratio [HR] 0.63; 95% CI 0.45, 0.87; P=0.006), reduction of MRA dose (HR 0.62; 95% CI 0.45, 0.87; P=0.006), and total adjusted hyperkalemia events/100 person-years (77.7 vs. 118.2; HR 0.66; 95% CI 0.53, 0.81; P<0.001) were lower with patiromer. Hyperkalemia-related morbidity-adjusted events (win ratio 1.53, P<0.001) and total RAASi use score (win ratio 1.25, P=0.048) favored the patiromer arm. Adverse events were similar between groups. Conclusion Concurrent use of patiromer and high-dose MRAs reduces the risk of recurrent hyperkalemia (ClinicalTrials.gov: NCT03888066).
Ritonavir-boosted nirmatrelvir (RBN) has been authorized recently in several countries as an orally active anti-SARS-CoV-2 treatment for patients at high risk of progressing to severe COVID-19 disease. Nirmatrelvir is the active component against the SARS-CoV-2 virus, whereas ritonavir, a potent CYP3A inhibitor, is intended to boost the activity of nirmatrelvir by increasing its concentration in plasma to ensure persistence of antiviral concentrations during the 12-hour dosing interval. RBN is involved in many clinically important drug-drug interactions both as perpetrator and as victim, which can complicate its use in patients treated with antiseizure medications (ASMs). Interactions between RBN and ASMs are bidirectional. As perpetrator, RBN may increase the plasma concentration of a number of ASMs that are CYP3A4 substrates, possibly leading to toxicity. As victims, both nirmatrelvir and ritonavir are subject to metabolic induction by concomitant treatment with potent enzyme-inducing ASMs (carbamazepine, phenytoin, phenobarbital and primidone). According to US and European prescribing information, treatment with these ASMs is a contraindication to the use of RBN. Although remdesivir is a valuable alternative to RBN, it may not be readily accessible in some settings due to cost and/or need for intravenous administration. If remdesivir is not an appropriate option, either bebtelovimab or molnupiravir may be considered. However, evidence about the clinical efficacy of bebtelovimab is still limited, and molnupiravir, the only orally active alternative, is deemed to have appreciably lower efficacy than RBN and remdesivir.
Purpose: Cardiovascular disease in women is frequently under-diagnosed and under-treated. Numerous heart centers for women have opened throughout the world to address these disparities; however, there is a paucity of data regarding participants' perspectives. The current study assesses motivation to participate and perceived benefits in attending a heart center for women (HCW) in Jerusalem, Israel. Methods: This study utilized qualitative methods to assess patients' motivation and perceived benefits to attending a women's heart center, particularly as they relate to gender medicine and single-sex staffing. A random sample of 42 clinic patients were asked to participate in interviews. Inclusionary criteria consisted of previous cardiovascular event, active cardiac symptom or three or more cardiovascular disease risk factors. Exclusionary criteria consisted of pregnancy, type 1 diabetes requiring insulin, psychiatric diagnosis that precluded participation, dementia, or other multidisciplinary clinic participation. Interviews were audio recorded and transcribed verbatim. Qualitative data analysis followed Braun and Clarke's methodology of thematic analysis. Results: The single-sex and gender medicine aspects did not motivate women to attend the HCW, although some participants perceived this as beneficial in retrospect. Women reported that the clinic visit enhanced their knowledge and awareness of issues related to heart disease in women as well as personal health benefits. They reported benefitting from the holistic approach, consideration of their lifestyle, the staff's expression of concern, personalized attention, common language, and feeling understood. Conclusion: This study describes the patient experience in an all-female HCW, highlighting their motivation for attendance and perceived benefits. While they did not actively seek women-centered care, women reported educational and care provision benefits to their attendance. The care attributes that women identified as beneficial typify the person-centered approach to care. These findings may inform both the design and evaluation of medical care facilities that aim to address the sex and gender disparities in cardiology as well as other medical specialties.
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974 members
Sharona Even-Ram
  • Goldyne Savad Institute of Gene Therapy
Avraham Zini
  • Department of Community Dentistry
Nitzan Bichacho
  • Department of Prosthodontics - RE Goldstein center for Esthetic Dentistry and clinical research
Ari Kupietzky
  • Department of Pediatric Dentistry
Yehuda Zadik
  • Department of Oral Medicine
Jerusalem, Israel