Multisystemic inflammatory syndrome in children and the BNT162b2 vaccine: a nationwide cohort study.

Multisystemic inflammatory syndrome in children (MIS-C) is a rare, severe, post-infectious hyperinflammatory condition that occurs after COVID-19 infection. In this study, we aimed to demonstrate the risk reduction of MIS-C and severe MIS-C after Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccination. This nationwide cohort study included 526,685 PCR-confirmed COVID-19 cases (age < 19 years), of whom 14,118 were fully vaccinated prior to COVID-19 infection. MIS-C cases were collected from all hospitals in Israel from April 2020 through November 2021. The MIS-C rates were calculated among two COVID-19 populations: positive PCR confirmed cases and estimated COVID-19 cases (PCR confirmed and presumed). Vaccination status was determined from Ministry of Health (MoH) records. The MIS-C risk difference (RD) and 95% confidence intervals (95%CI) between vaccinated and unvaccinated patients are presented. Overall, 233 MIS-C cases under the age of 19 years were diagnosed and hospitalized in Israel during the study period. Among the estimated COVID-19 cases, MIS-C RD realistically ranged between 2.1 [95%CI 0.7-3.4] and 1.0 [95%CI 0.4-1.7] per 10,000 COVID-19 cases. For severe MIS-C, RD realistically ranged between 1.6 [95%CI 1.3-1.9] and 0.8 [95%CI 0.7-1.0], per 10,000 COVID-19 cases. Sensitivity analysis was performed on a wide range of presumed COVID-19 rates, demonstrating significant RD for each of these rates. CONCLUSION: This research demonstrates that vaccinating children and adolescents against COVID-19 has reduced the risk of MIS-C during the study period. WHAT IS KNOWN: • Most of the published literature regarding vaccine effectiveness is based on case-control studies, which are limited due to small sample sizes and the inability to fully estimate the risk of MIS-C among vaccinated and unvaccinated children and adolescents. • The known underestimation of COVID-19 diagnosis among children and adolescents is challenging, as they often have few to no symptoms. WHAT IS NEW: • Significant risk difference was found in favor of the vaccinated group, even after including extreme assumptions regarding the underdiagnosed COVID-19 rate. • During this nationwide study period, it was found that vaccinating children and adolescents reduced the risk of MIS-C and its complications.

Post-Ebola sequelae among Ebola child survivors in Sierra Leone.

BACKGROUND: There are limited data regarding the long-term health effects of child survivors of the 2013-2016 West African Ebola virus disease (EVD) outbreak. Here, we assess post-Ebola sequelae among EVD child survivors by comparing the self-reported symptoms between EVD child survivors and their close household contacts over one year after the end of the outbreak. METHODS: EVD child survivors(n=159) and their close contacts(n=303) were enrolled in Western and Eastern Sierra Leone. Demographics and self-reported symptoms data were collected using an interviewer-administered questionnaire. We compared a list of self-reported symptoms between EVD child survivors and their close household contacts using backward stepwise logistic regression. RESULTS: EVD child survivors were more likely to be orphans compared to their close contacts. Musculoskeletal, ocular, auditory and neurological symptoms were more prevalent among Ebola child survivors than their close contacts (p<0.001). Joint pain and headache were the most common self-reported symptoms in EVD child survivors and their close contacts. Joint pain (AOR=2.633; 95 % CI:1.31-5.28, p=0.006), eye pain (AOR=4.56;95 %CI: 2.16-9.64, p<0.001), hearing loss (AOR=3.85; 95 %CI: 1.15-12.87, p=0.029), memory impairment (AOR=7.76;0.95 %CI: 1.34-45.01 p=0.022), mood changes (AOR=5.07; 95 %CI: 2.35-10.94, p<0.001) were more common among survivors than their contacts. CONCLUSIONS: Our data suggest that EVD child survivors have higher odds than their close contacts of suffering from musculoskeletal, ophthalmic, auditory and neurological impairment more than a year after the end of the EVD outbreak. Routine screening, treatment and monitoring of these symptoms is required to prevent long-term disability among EVD child survivors.

Inferring Numbers of Wild Poliovirus Excretors Using Quantitative Environmental Surveillance.

Response to and monitoring of viral outbreaks can be efficiently focused when rapid, quantitative, kinetic information provides the location and the number of infected individuals. Environmental surveillance traditionally provides information on location of populations with contagious, infected individuals since infectious poliovirus is excreted whether infections are asymptomatic or symptomatic. Here, we describe development of rapid (1 week turnaround time, TAT), quantitative RT-PCR of poliovirus RNA extracted directly from concentrated environmental surveillance samples to infer the number of infected individuals excreting poliovirus. The quantitation method was validated using data from vaccination with bivalent oral polio vaccine (bOPV). The method was then applied to infer the weekly number of excreters in a large, sustained, asymptomatic outbreak of wild type 1 poliovirus in Israel (2013) in a population where >90% of the individuals received three doses of inactivated polio vaccine (IPV). Evidence-based intervention strategies were based on the short TAT for direct quantitative detection. Furthermore, a TAT shorter than the duration of poliovirus excretion allowed resampling of infected individuals. Finally, the method documented absence of infections after successful intervention of the asymptomatic outbreak. The methodologies described here can be applied to outbreaks of other excreted viruses such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), where there are (1) significant numbers of asymptomatic infections; (2) long incubation times during which infectious virus is excreted; and (3) limited resources, facilities, and manpower that restrict the number of individuals who can be tested and re-tested.

Earlier Outbreak Detection-A Generic Model and Novel Methodology to Guide Earlier Detection Supported by Data From Low- and Mid-Income Countries.

Infectious disease outbreaks can have significant impact on individual health, national economies, and social well-being. Through early detection of an infectious disease, the outbreak can be contained at the local level, thereby reducing adverse effects on populations. Significant time and funding have been invested to improve disease detection timeliness. However, current evaluation methods do not provide evidence-based suggestions or measurements on how to detect outbreaks earlier. Key conditions for earlier detection and their influencing factors remain unclear and unmeasured. Without clarity about conditions and influencing factors, attempts to improve disease detection remain ad hoc and unsystematic. Methods: We developed a generic five-step disease detection model and a novel methodology to use for data collection, analysis, and interpretation. Data was collected in two workshops in Southeast Europe (n = 33 participants) and Southern and East Africa (n = 19 participants), representing mid- and low-income countries. Through systematic, qualitative, and quantitative data analyses, we identified key conditions for earlier detection and prioritized factors that influence them. As participants joined a workshop format and not an experimental setting, no ethics approval was required. Findings: Our analyses suggest that governance is the most important condition for earlier detection in both regions. Facilitating factors for earlier detection are risk communication activities such as information sharing, communication, and collaboration activities. Impeding factors are lack of communication, coordination, and leadership. Interpretation: Governance and risk communication are key influencers for earlier detection in both regions. However, inadequate technical capacity, commonly assumed to be a leading factor impeding early outbreak detection, was not found a leading factor. This insight may be used to pinpoint further improvement strategies.

Earlier detection of public health risks - Health policy lessons for better compliance with the International Health Regulations (IHR 2005): Insights from low-, mid- and high-income countries.

The International Health Regulations (IHR 2005) require all Member States to build and maintain the capacities to prevent, detect and respond to public health emergencies. Early detection of public health risks is one of the core functions. In order to improve surveillance and detection, a better understanding of the health system conditions and their influencing factors are needed. The Israeli Ministry of Health/IHR National Focal Point held a workshop to elucidate health system conditions and their influencing factors that enable earlier detection. The workshop methodology employed a stepwise, small working group analysis approach to elucidate the conditions and their influencing factors affecting each stage of recognition, assessment, and reporting of infectious disease outbreaks, at the local, regional and national levels. In order to detect public health risks earlier, the detection process needs to be moved closer to the local communities and start with building capacity within communities. Building capacity and engaging with local and diverse communities requires significant changes in the governance approach and include information sharing, multi-sectoral communication and coordination across various levels before, during and after public health emergencies. Across the regions, low-, mid- and high-income countries seem to struggle more with governance and information sharing rather than with technical capacities and capabilities.

Outbreak of human leptospirosis linked to contaminated water bodies in Northern Israel, June to August 2018.

We report preliminary findings of a large outbreak of human leptospirosis with 36 confirmed/probable and 583 suspected cases from June-August 2018, linked to contaminated water bodies in Northern Israel. There was a travel-associated case in Germany; additional cases are being investigated in other countries. The presumed chain of transmission, implicating wild boar and cattle, raises multiple challenges for risk assessment, risk management and risk communication currently being addressed by a public health response team.

Ongoing mumps outbreak in Israel, January to August 2017.

In Israel, 262 mumps cases were registered between 1 January and 28 August 2017 despite a vaccine coverage of ≥ 96%. The majority (56.5%) of cases were adolescents and young adults between 10 and 24 years of age. Nearly twice as many cases were reported in males than in females. Sequence information identified genotype G and suggested specific transmission chains in different religious communities, with the Muslim population in Jerusalem being most severely affected.

The weight of MMRV-related febrile convulsions among other clinical factors contributing to febrile convulsions in children.

BACKGROUND: It was previously demonstrated that MMRV vaccine causes a higher rate of febrile convulsions (FC) compared to the MMR vaccine. Additional risk factors for FC include age, familial tendency, day care attendance, viral diseases, complications at birth and developmental delay. OBJECTIVE: We evaluated the relative and attributable risk of FC for vaccinees' age, ethnicity, low birth weight, preterm birth and MMRV vaccination in 10-24 months old children. METHODS: Data on medical history and vaccination were extracted from data warehouses of Clalit Health Services and Israel's Ministry of Health and linked on an individual record level for 90,294 MMR- and 8344 MMRV-vaccinees. A retrospective study design was used to reveal the risk factors associated with FC in study participants. RESULTS: During the second week after immunization, an elevated relative risk of FC was demonstrated in MMRV-recipients (adjusted RR=2.16 (95%CI: 1.01; 4.64)). However, the cumulative incidence of FC during the entire 40-day observation period did not differ between the MMR and MMRV vaccinees. The MMRV-specific attributable risk of FC was not statistically significant at any point of observation period and was exceedingly low compared to other risk factors, equaling 5.3 FC cases per 10,000 vaccinees (95%CI: -1.4; 12.2). DISCUSSION: Our findings demonstrate that MMRV-associated FC in 10-24 months old contributes very marginally to the overall rate of FC in this population. CONCLUSION: Given the low number of MMRV-specific FC cases, their transient nature and the benefit of vaccination, the overall benefit-risk of the vaccine can be considered favourable. Nonetheless, the option of separate immunization with MMR+V should be offered to parents, in order to maintain sufficient vaccine uptake in the population.

EMR-based medication adherence metric markedly enhances identification of nonadherent patients.

OBJECTIVES: To determine whether addition of written-prescription data to existing adherence measures improves identification of nonadherent patients and prediction of changes in low-density lipoprotein (LDL) cholesterol. STUDY DESIGN: Retrospective database analysis of all health plan members prescribed a statin in 2008 and followed through 2010. METHODS: We examined statin use in a 4-millionmember health plan with 100% electronic medical record coverage. A novel type of medication possession ratio (MPR), integrating prescribed with dispensed medication data, was developed. This measure, MPRp, was compared with a standard dispensed-only adherence measure, MPRd. Adherence below 20% was considered nonadherence. The 2 adherence measures were compared regarding (1) the number of patients identified as nonadherent, (2) percent changes in LDL from study enrollment to study termination, and (3) receiver-operator curves assessing the association between adherence and a 24% decrease in LDL. RESULTS: A total of 67,517 patients received 1,386,270 written prescriptions over the 3-year period. MPRp identified 93% more patients as nonadherent than did MPRd (P <.001). These newly identified patients exhibited minimal LDL decreases over the course of the study. Adherence by MPRp was more strongly associated with decreases in LDL than was adherence by MPRd (area under the curve 0.815 vs 0.770; P <.001). During the study period, 18.2% of patients did not fill any prescriptions and were thus unidentifiable by dispensed-only measures. CONCLUSIONS: Addition of written-prescription data to adherence measures identified nearly twice the number of nonadherent patients and markedly improved prediction of changes in LDL.

Effect of Traumeel S on cytokine profile in a cecal ligation and puncture (CLP) sepsis model in rats.

BACKGROUND: Sepsis results in significant morbidity and mortality, with current treatment options limited with respect to efficacy as well as safety. The complex homeopathic remedy Traumeel S has been shown to have both anti-inflammatory and immunostimulatory effects in the in vitro setting. OBJECTIVES: The objective was to explore the effects of Traumeel S in an in vivo setting, using a cecal ligation and puncture (CLP) sepsis model in rats, evaluating the effects of the medication on cytokine activity. DESIGN: Sepsis was induced in 30 rats using accepted CLP methodology. Following the procedure, rats were randomly allocated to receive an intraperitoneal injection of either Traumeel S (n=15) or normal saline (n=15). At 6 hours post-CLP, serum cytokines (interleukin [IL]-1ß, tumor necrosis factor-α, IL-6, and IL-10) were evaluated. RESULTS: IL-1ß levels were significantly higher in the treatment group (p=0.03) with no significant differences found between the groups with respect to the other cytokines tested. CONCLUSIONS: In contrast to in vitro studies, Traumeel significantly increased IL-1ß levels in an in vivo model, without influencing other cytokines. IL-1ß is a proinflammatory cytokine that has been shown to have a protective effect in the CLP rat model. Further research is warranted to examine this finding, as well as its clinical implications.

Hypnosis and acupuncture (hypnopuncture) for prurigo nodularis: a case report.

Prurigo Nodularis (PN) is a chronic pruritic skin condition for which current conventional therapies are of limited benefit and with potentially toxic effects. Acupuncture--the insertion of thin needles at specific points on the skin--has been shown to alleviate itching through a number of itch-associated mediator effects. Hypnosis has been shown to modify and reduce the intensity of itching as well. A 44 year-old woman presented with a 30-year history of a diffuse itchy rash diagnosed as PN. She had tried various antihistamine and corticosteroid medications, to no avail. A treatment regimen using hypnosis and acupuncture (hypnopuncture) was initiated, with significant reduction in the itching, size and number of skin lesions. Hypnopuncture may offer a synergistic and augmented response to treatment, though further research is needed to understand the true benefits of this combined regimen.

Hormesis and homeopathy: bridge over troubled waters.

Homeopathy is an empirical method of treatment. Hormesis, while stemming from within the rationalist tradition, has yet to be explained according to current pharmacological theory. Both share in common sub-threshold doses of toxic substances and an initial semi-toxicological insult followed by a greater compensatory (or healing) response. We question whether the differences between these fields may be amenable to scientific research. We identify five cardinal differences between homeopathy and hormesis: (1) Hormesis is a universal phenomenon, while homeopathy is highly specific; (2) Hormesis uses only measurable quantities of compounds, as opposed to homeopathy, which frequently administers medicines at dilutions far beyond the material range; (3) Preparation of hormetic solutions follows standard laboratory procedure, while homeopathy requires a sequential series of dilutions, each followed by vigorous shaking ('succussion'); (4) The effects of hormesis are moderate and temporary, while homeopathy claims curative and permanent responses and (5) Hormesis is a lab phenomenon observed primarily in healthy organisms, whereas homeopathy is a mode of treatment administered primarily to ailing individuals. We believe that all five of these differences are amenable to scientific investigation, and suggest comparing succussed to non-succussed diluted solutions as an optimal first evaluation. We conclude that while certain differences exist between hormesis and homeopathy, hormesis may in fact be a subset of homeopathy.

[Validation of a Hebrew translation of the Gastroparesis Cardinal Symptom Index (GCSI)].

BACKGROUND: Symptom checklists used in clinical research of gastroparesis have not been evaluated for reliability or validity. The Gastroparesis Cardinal Symptom Index (GCSI) is a reliable, validated measure whereby patients score three groups of symptoms: nausea/vomiting, postprandial fullness/early satiety and bloating. AIM: The purpose of this study was to translate the GCSI into Hebrew and then validate the language of the translation for use in future studies. METHODOLOGY: The measure was first translated into Hebrew and then back-translated to English, followed by a comparison of the two versions. The English and Hebrew versions were then completed by 40 healthy bilingual volunteers, using a cross-over design, with half answering the English version first while the other half replied to the Hebrew version first. RESULTS: The internal consistency for both measures was moderate, the English slightly lower than the Hebrew (Cronbach's alpha 0.67 vs. 0.72). Intra-class correlation values were larger than 0.7 for all but one of the symptoms (item 3, "vomiting"), although a Wilcoxian signed-rank test found this correlation to be of borderline significance (z=-1.63, p=0.50). CONCLUSIONS: The Hebrew translation of the GCSI is valid for use in clinical research, although further psychometric testing is needed to test its value for this purpose. This manuscript describes the stages of measurement, translation and language validation, the difficulties that researches face and possible solutions when researches choose to use a measure which was developed in a different language.

Ecoepidemiology of cutaneous leishmaniasis outbreak, Israel.

A total of 161 cases of cutaneous leishmaniasis caused by Leishmania tropica occurred in the Jerusalem district during 2004-2005; 127 (79%) cases were in a town just outside Jerusalem. Environmental models suggest that in the context of global warming, this outbreak has the potential to extend into Jerusalem.

Acupuncture for psychiatric illness: a literature review.

The use of complementary and alternative medicine (CAM) is on the rise, especially among psychiatric patients. Acupuncture is considered a safe and effective treatment modality, and traditional Chinese medicine teaches that acupuncture harmonizes the body's energies. Scientific research has found that acupuncture increases a number of central nervous system hormones (ACTH, beta-endorphins, serotonin, and noradrenaline) and urinary levels of MHPG-sulfate, an adrenergic metabolite inversely related to the severity of illness in schizophrenics. Acupuncture can have positive effects on depression and anxiety, although evidence is still lacking as to its true efficacy for these conditions. To the authors' knowledge, no trials have been conducted for schizophrenia, and researchers evaluating acupuncture in cases of substance abuse have found conflicting results. Further research is warranted.

Herbal medicine and epilepsy: proconvulsive effects and interactions with antiepileptic drugs.

The use of complementary and alternative medicine is on the rise, including among patients with epilepsy. Herbal medicine, one of the most popular forms of CAM, is considered to be both safe and effective by most consumers. Yet many herbs may increase the risk for seizures, through intrinsic proconvulsant properties or contamination by heavy metals, as well as via effects on the cytochrome P450 enzymes and P-glycoproteins, altering antiepileptic drug (AED) disposition. Herb-drug interactions may be difficult to predict, especially since the quality and quantity of active ingredients are often unknown. Since most patients do not inform their physicians that they are taking herbal medicines, health care professionals must initiate a dialogue in order to prevent complications with the combined regimen. At the same time, further research is required regarding the effect of herbs on seizure activity and interactions with AED treatment.

The effect of the homeopathic remedies Arnica montana and Bellis perennis on mild postpartum bleeding--a randomized, double-blind, placebo-controlled study--preliminary results.

OBJECTIVE: To evaluate the effect of Arnica Montana and Bellis perennis on postpartum blood loss. DESIGN: Double blind, placebo-controlled, randomized, clinical trial. SETTING: Department of Gynecology, Shaare Zedek Medical Center, Jerusalem. INTERVENTIONS: Forty parturients were randomized to one of three groups: Arnica montana C6 and Bellis perennis C6 (n=14), Arnica montana C30 and Bellis perennis C30 (n=14), or double placebo (n=12). After 48 h the Arnica/placebo was halted, and patients continued the Bellis/placebo until cessation of lochia. MAIN OUTCOME MEASURES: Hemoglobin levels (Hb) at 48 and 72 h postpartum. RESULTS: At 72 h postpartum, mean Hb levels remained similar after treatment with homeopathic remedies (12.7 versus 12.4) as compared to a significant decrease in Hb levels in the placebo group (12.7 versus 11.6; p<0.05), in spite of less favorable initial characteristics of the treatment group. The mean difference in Hb levels at 72 h postpartum was -0.29 (95% CI -1.09; 0.52) in the treatment group and -1.18 (95% CI -1.82; -0.54) in the placebo group (p<0.05). CONCLUSION: Treatment with homeopathic Arnica montana and Bellis perennis may reduce postpartum blood loss, as compared with placebo.

Homeopathy in emergency medicine.

BACKGROUND: Use of homeopathy is not frequently reported in critically ill patients. We describe our experience treating such patients homeopathically in the emergency room, on the wards, and in the intensive care unit of conventional hospitals in Austria and Israel. METHODS: We describe a case series of patients treated in the ER for multiple casualty incidents, two case reports of remarkable cures in the ICU, and two RCTs demonstrating the efficacy of homeopathy in septic and intubated patients. RESULTS: A case series documents favorable results in homeopathic treatment of patients in the ER and wards after multiple casualty incidents. Two case reports narration e remarkable homeopathic cures to imminently terminal illnesses. Finally, homeopathy was demonstrated effective as compared with placebo in improving long-term survival in severely ill septic patients and in hastening extubation ICU patients. CONCLUSIONS: Our report suggests that homeopathy may be applicable even for critically ill patients. We discuss the obstacles encountered, including a dearth of tools for successful homeopathic prescription in these situations, suspicion and lack of cooperation by patients and conventional colleagues, and the highly suppressive nature of concomitant conventional therapies. We suggest the development of algorithms and other tools to aid rapid homeopathic prescription in critical care patients and discuss the importance of familiarizing physicians and medical students with homeopathy in order to facilitate communication and cooperation between these complementary branches of medicine.