Data-Driven Assessment of Adolescents' Mental Health During the COVID-19 Pandemic.

OBJECTIVE: Adolescents' mental health was severely compromised during the COVID-19 pandemic. Longitudinal real-world studies on changes in the mental health of adolescents during the later phase of the pandemic are limited. We aimed to quantify the effect of COVID-19 pandemic on adolescents' mental health outcomes based on electronic health records. METHOD: This was a retrospective cohort study using the computerized database of a 2.5 million members, state-mandated health organization in Israel. Rates of mental health diagnoses and psychiatric drug dispensations were measured among adolescents 12 to 17 years of age with and without pre-existing mental history, for the years 2017 to 2021. Relative risks were computed between the years, and interrupted time series (ITS) analyses evaluated changes in monthly incidence rates of psychiatric outcomes. RESULTS: The average population size was 218,146 in 2021. During the COVID-19 period, a 36% increase was observed in the incidence of depression (95% CI = 25-47), 31% in anxiety (95% CI = 23-39), 20% in stress (95% CI = 13-27), 50% in eating disorders (95% CI = 35-67), 25% in antidepressant use (95% CI = 25-33), and 28% in antipsychotic use (95% CI = 18-40). A decreased rate of 26% (95% CI = 0.80-0.88) was observed in ADHD diagnoses. The increase of the examined outcomes was most prominent among youth without psychiatric history, female youth, general secular Jewish population, youth with medium-high socioeconomic status, and those 14 to 15 years of age. ITS analysis confirmed a significantly higher growth in the incidence of psychiatric outcomes during the COVID-19 period, compared to those in previous years. CONCLUSION: This real-world study highlights the deterioration of adolescents' mental health during the COVID-19 pandemic and suggests that youth mental health should be considered during health policy decision making. DIVERSITY & INCLUSION STATEMENT: We worked to ensure sex and gender balance in the recruitment of human participants. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We actively worked to promote sex and gender balance in our author group. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

Long covid outcomes at one year after mild SARS-CoV-2 infection: nationwide cohort study.

OBJECTIVES: To determine the clinical sequelae of long covid for a year after infection in patients with mild disease and to evaluate its association with age, sex, SARS-CoV-2 variants, and vaccination status. DESIGN: Retrospective nationwide cohort study. SETTING: Electronic medical records from an Israeli nationwide healthcare organisation. POPULATION: 1 913 234 Maccabi Healthcare Services members of all ages who did a polymerase chain reaction test for SARS-CoV-2 between 1 March 2020 and 1 October 2021. MAIN OUTCOME MEASURES: Risk of an evidence based list of 70 reported long covid outcomes in unvaccinated patients infected with SARS-CoV-2 matched to uninfected people, adjusted for age and sex and stratified by SARS-CoV-2 variants, and risk in patients with a breakthrough SARS-CoV-2 infection compared with unvaccinated infected controls. Risks were compared using hazard ratios and risk differences per 10 000 patients measured during the early (30-180 days) and late (180-360 days) time periods after infection. RESULTS: Covid-19 infection was significantly associated with increased risks in early and late periods for anosmia and dysgeusia (hazard ratio 4.59 (95% confidence interval 3.63 to 5.80), risk difference 19.6 (95% confidence interval 16.9 to 22.4) in early period; 2.96 (2.29 to 3.82), 11.0 (8.5 to 13.6) in late period), cognitive impairment (1.85 (1.58 to 2.17), 12.8, (9.6 to 16.1); 1.69 (1.45 to 1.96), 13.3 (9.4 to 17.3)), dyspnoea (1.79 (1.68 to 1.90), 85.7 (76.9 to 94.5); 1.30 (1.22 to 1.38), 35.4 (26.3 to 44.6)), weakness (1.78 (1.69 to 1.88), 108.5, 98.4 to 118.6; 1.30 (1.22 to 1.37), 50.2 (39.4 to 61.1)), and palpitations (1.49 (1.35 to 1.64), 22.1 (16.8 to 27.4); 1.16 (1.05 to 1.27), 8.3 (2.4 to 14.1)) and with significant but lower excess risk for streptococcal tonsillitis and dizziness. Hair loss, chest pain, cough, myalgia, and respiratory disorders were significantly increased only during the early phase. Male and female patients showed minor differences, and children had fewer outcomes than adults during the early phase of covid-19, which mostly resolved in the late period. Findings remained consistent across SARS-CoV-2 variants. Vaccinated patients with a breakthrough SARS-CoV-2 infection had a lower risk for dyspnoea and similar risk for other outcomes compared with unvaccinated infected patients. CONCLUSIONS: This nationwide study suggests that patients with mild covid-19 are at risk for a small number of health outcomes, most of which are resolved within a year from diagnosis.

Results of an early second PCR test performed on SARS-CoV-2 positive patients may support risk assessment for severe COVID-19.

Identifying patients at increased risk for severe COVID-19 is of high priority during the pandemic as it could affect clinical management and shape public health guidelines. In this study we assessed whether a second PCR test conducted 2-7 days after a SARS-CoV-2 positive test could identify patients at risk for severe illness. Analysis of a nationwide electronic health records data of 1683 SARS-CoV-2 positive individuals indicated that a second negative PCR test result was associated with lower risk for severe illness compared to a positive result. This association was seen across different age groups and clinical settings. More importantly, it was not limited to recovering patients but also observed in patients who still had evidence of COVID-19 as determined by a subsequent positive PCR test. Our study suggests that an early second PCR test may be used as a supportive risk-assessment tool to improve disease management and patient care.

[Cyanides--treatment beneath the shade of terror].

Although the use of cyanides as warfare agents has not been documented since the Iran-Iraq war in the 1980s, there are rising fears of cyanide being used by terrorists. An Al-Qaeda terror plot to use cyanide gas in the London Underground was foiled in 2002. The threat of similar events becomes more imminent in light of the terror attacks in our country and worldwide, accompanied by statements and threats by fundamentalist leaders to employ chemical weapons. Therefore, mass-intoxication with cyanides is not merely a hypothetical scenario. The treatment of cyanide poisoning is under constant evaluation and there is no international consensus on the subject. The medical treatment of victims at the scene and in hospitals should be rapid and efficient. Current treatment dictates establishing an intravenous line and a slow rate of administration of antidotes. Both demands are not feasible in this specific mass casualty event. The clinical signs of cyanide poisoning are complex, variable and not necessarily obvious for the medical team. There is great interest in reconsidering the existing treatment protocols for cyanide intoxication in light of current research. This review describes the mechanisms of cyanide toxicity, clinical signs of exposure, and current treatment protocols in use worldwide. On the basis of this evidence we suggest a medical treatment protocol for a mass casualty event caused by cyanide.

Lessons learned from clinical anthrax drills: evaluation of knowledge and preparedness for a bioterrorist threat in Israeli emergency departments.

STUDY OBJECTIVE: Emergency department (ED) physicians and nurses are considered critical sentinels of a bioterrorist attack. We designed a special hospital drill to test EDs' response to inhalational anthrax and assess the level of preparedness for anthrax bioterrorism. We hypothesized that the occurrence of such a drill in an ED would improve the knowledge of its physicians, even those who had not actually participated in the drill. METHODS: We conducted 23 drills at all Israeli general hospitals' EDs. An actor entered the walk-in triage area, simulating a febrile patient with lower respiratory complaints. A chest radiograph with mediastinal widening, as can be seen in early anthrax disease, was planted in the hospital's imaging results system. Patients were instructed to give additional epidemiologic clues, such as having a few friends with a similar syndrome. Either before or after the drills, we distributed multiple choice tests about diagnosis and management of anthrax to the 115 senior emergency physicians at these hospitals. RESULTS: In 91% of EDs, a decision to admit the patient was made. Sixty-one percent included anthrax in the differential diagnosis and activated the appropriate protocols. Only 43% contacted all relevant officials. Average score on the anthrax tests was 58 (of 100). Physicians who were tested before the drill (in their institution) achieved a mean score of 54.5, whereas those who were tested after their ED had been exercised achieved a mean score of 59.3. CONCLUSION: A national framework of drills on bioterrorism can help estimate and potentially augment national preparedness for bioterrorist threats. It is not, on its own, an effective educational tool. More emphasis should be given to formal accredited continuing medical education programs on bioterrorism, especially for emergency physicians and ED nurses, who will be in the front line of a bioterrorist attack.

Civilian adult self injections of atropine-trimedoxime (TMB4) auto-injectors.

INTRODUCTION: The clinical effects of self injections of atropine-trimedoxime auto-injectors distributed to the civilian population as a field antidote for nerve agent attack were assessed. METHODS: Data on self injections by adults (> or = 18 years) were collected from the Israel Poison Information Center and a hospital Emergency Department's records during a 2-year period. The data included demographics, time interval from injection, type of auto-injector, clinical manifestations and atropinization score. RESULTS: Sixty-five patients, all with unintentional self injections, were reported. Systemic atropine effects were observed in 24 patients, but no severe atropinization. The atropinization score was significantly higher in the 2 mg atropine dose group than in the two lower dose groups, which were in the normal range. No specific adverse effects attributable to trimedoxime were observed. Intravenous fluids and physostigmine were not required. CONCLUSION: Only mild reactions were observed following self-injection of atropine trimedoxime auto-injectors in adults, attesting to their relative safety under these conditions.

[Political poisoning with dioxins--a weapon of chemical "disgracefulness"].

The recent attempt to poison Ukrainian President, Viktor Yuschenko with dioxins, raised public concern regarding this toxic chemical. In industrial countries, there is a constitutive exposure of humans to dioxin compounds, which are formed as by-products in manufacturing processes of various chlorinated organic chemicals and in waste incinerators. Dioxins are extremely stable in the environment and have a low turnover rate in the body--sometimes they are detected years after the original exposure. Of the dioxins, the most notoriously famous is the TCDD (2,3,7,8 tetrachlorodibenzo-p-dioxin). Dioxins exhibit high acute toxicity in various animal species. Humans, however, are considered less susceptible and so far there were no reported deaths following acute dioxin poisoning. Nevertheless, numerous adverse health effects are attributed to dioxin exposure. The most prominent is the chloracne--an acute acneiform eruption, usually appearing on facial skin. There is a solid evidence base that some dioxins are carcinogens. Other long-term deleterious effects of dioxin include: immunosuppression, effects on reproduction, impairments in developmental, neurological and cognitive functions in infants, increased risk for diabetes and cardiovascular diseases and various hormonal alterations. The action of dioxins resembles that of hormones, since their toxicity is mostly receptor-mediated. Dioxins manifest their toxicity in extremely low concentrations. Although there are compounds that exhibit their biological activity at even lower dose range (e.g. nerve gases), this potency of dioxins is considered extraordinary, since there is an every-day exposure to dioxins through environmental vectors mostly via the food chain. Until now, there is no antidotal cure for dioxins, but only symptomatic treatment combined with techniques that accelerate its excretion rate from the body.

OP or not OP: the medical challenge at the chemical terrorism scene.

Since the 1995 Tokyo subway sarin attack, terrorist attacks involving weapons of mass destruction or other industrial chemicals present worldwide security and health concerns. On-scene medical triage and treatment in such events is crucial to save as many lives as possible and minimize the deleterious effects of the toxic agent involved. Since there are many chemicals that can be used as potential terrorist weapons, the medical challenge for the emergency medical services (EMS) is a combination of: (1) recognizing that a chemical terrorist attack (non-conventional) has occurred; and (2) identifying the toxic agent followed by proper antidotal treatment. The latter must be done as quickly as possible, preferably on-scene. The most valuable decision at this stage should be whether the agent is organophosphate (OP) or not OP, based on clinical findings observed by pre-trained, first responders. This decision is crucial, since only OP intoxication has readily available, rapidly acting, onscene, specific agents such as atropine and one of the oximes, preferably administered using autoinjectors. Due to the lack of a specific antidote, exposure to other agents (such as industrial chemicals, e.g., chlorine, bromide, or ammonia) should be treated on-scene symptomatically with non-specific measures, such as decontamination and supportive treatment. This paper proposes an algorithm as a cognitive framework for the medical teams on-scene. This algorithm should be part of the medical team's training for preparedness for chemical terrorist attacks, and the team should be trained to use it in drills. Implementing this path of thinking should improve the medical outcome of such an event.

[Medical management in the chemical terrorism scene].

The Tokyo subway sarin attack in March 1995 demonstrated the importance of preparedness toward a chemical terrorist attack. Emergency medical teams on the scene are valuable, beside the medical treatment of casualties, in the cognition of toxicant involvement and later in the recognition of the specific toxidrome involved. The chemical terrorism scene is a contaminated area; therefore, first responders have to be protected from both percutaneous and inhalational exposure to toxic materials. This protection is also against secondary evaporation (gas-off) from contaminated casualty, hence the importance of disrobing casualties on the scene as soon as possible. Once the recognition of toxicological involvement have been made, the next crucial decision is whether the clinical toxidrome is of cholinergic toxicity (e.g. organophosphate or carbamate intoxication) in which there are automatic injectors for treatment available on the scene, or any other toxidrome (such as irritation or vesicants) in which, beside general measures, like oxygen delivery and airway support, there is not a specific antidotal treatment on the scene. The clinical detection and identification of the chemical toxidrome involved is of utmost importance since it promotes the antidotal treatment quickly and efficiently. The key to the medical management of such events is based on decisions that have to be taken as soon as possible according to the clinical judgment of medical teams on the scene.

Pharmacologic prophylaxis against nerve agent poisoning.

Nerve agent poisoning is characterized by the rapid progression of toxic signs, including hypersecretions, tremor, convulsions and profound brain damage. In the political arena of today's world, the threat of nerve agent use against military troops has prompted armies to search for prophylactic protection. The two main strategies for prophylaxis include biological scavengers that can bind or cleave nerve agents before they react with acetylcholinesterase, and antidotes as prophylactic treatment. Pyridostigmine is the current pretreatment for nerve agent poisoning and is in use by most of the armed forces in Western countries. However, since pyridostigmine barely crosses the blood-brain barrier it provides no protection against nerve agent-induced central injury. Pyridostigmine is ineffective when administered without post-exposure treatment adjuncts. Therefore, other directions for prophylactic treatment should be explored. These include combinations of carbamates (reversible AChE inhibitors) and central anticholinergics or NMDA receptor antagonists, benzodiazepines or partial agonists for benzodiazepine receptor, and other central AChE inhibitors approved for Alzheimer's disease. The transdermal route is an alternative way for delivering the prophylactic agent. Administration of prophylaxis can be extended also for civilian use during wartime.

Inherited and acquired interactions between ACHE and PON1 polymorphisms modulate plasma acetylcholinesterase and paraoxonase activities.

The 5.5 Mb chromosome 7q21-22 ACHE/PON1 locus harbours the ACHE gene encoding the acetylcholine hydrolyzing, organophosphate (OP)-inhibitable acetylcholinesterase protein and the paraoxonase gene PON1, yielding the OP-hydrolyzing PON1 enzyme which also displays arylesterase activity. In search of inherited and acquired ACHE-PON1 interactions we genotyped seven polymorphic sites and determined the hydrolytic activities of the corresponding plasma enzymes and of the AChE-homologous butyrylcholinesetrase (BChE) in 157 healthy Israelis. AChE, arylesterase, BChE and paraoxonase activities in plasma displayed 5.4-, 6.5-, 7.2- and 15.5-fold variability, respectively, with genotype-specific differences between carriers of distinct compound polymorphisms. AChE, BChE and arylesterase but not paraoxonase activity increased with age, depending on leucine at PON1 position 55. In contrast, carriers of PON1 M55 displayed decreased arylesterase activity independent of the - 108 promoter polymorphism. Predicted structural consequences of the PON1 L55M substitution demonstrated spatial shifts in adjacent residues. Molecular modelling showed substrate interactions with the enzyme variants, explaining the changes in substrate specificity induced by the Q192R substitution. Intriguingly, PON1, but not BChE or arylesterase, activities displayed inverse association with AChE activity. Our findings demonstrate that polymorphism(s) in the adjacent PON1 and ACHE genes affect each other's expression, predicting for carriers of biochemically debilitating ACHE/PON1 polymorphisms adverse genome-environment interactions.

Safety of biological/chemical respiratory protection filter for patients in need of oxygen supplementation.

BACKGROUND: During the 2003 war in Iraq, Israel faced the problem of supplying biological/chemical respiratory protection for a population in need of ventilator support. The devices in use were insufficient in terms of protective value, costs, and availability. An adaptor was developed to allow connection between respirators and the standard biological/chemical filter canister. OBJECTIVE: As part of the safety protocol for such a device, an investigation was made to determine the possibility of combustion of the biological/chemical filter canister, because of a possible exothermic reaction between the inspired oxygen-enriched air flow passing through the canister and the activated charcoal component of the filter. METHODS: A mechanical ventilator generated airflow with a frequency of 24 breaths per minute and a 500-mL tidal volume, for 90 minutes, through 14 standard filter canisters in a sealed chamber at a temperature of 25 degrees C and through seven canisters at a temperature of 30 degrees C. Incremental levels of oxygen (21-100%) were used for each set of canisters. The temperature of each filter was recorded throughout the examination. RESULTS: There was no elevation in the final temperature of the filters after 90 minutes of airflow with high oxygen levels. There were no signs of ignition. CONCLUSION: High oxygen levels passing through the activated carbon in the filter canister placed between the mechanical ventilator and the patient do not cause a combustion reaction, making it a safe means for respiratory protection for patients undergoing mechanical ventilation.

Clinical and immune responses after revaccination of israeli adults with the Lister strain of vaccinia virus.

BACKGROUND: During the winter of 2002-2003, the Israeli health authorities launched a campaign to vaccinate first responders against smallpox. METHODS: In an open study, 159 healthy, preimmunized adults, 24-52 years old, who participated in the campaign were vaccinated with the Lister strain of vaccinia virus by the multipuncture technique. The safety, immunogenicity, and reactogenicity of the vaccine were assessed. RESULTS: Successful vaccination rates were 61% and 56%, on the basis of clinical take and seroconversion, respectively. Adverse events among the vaccinees were minor. Seventy-nine (88%) of the 90 vaccinees with clinical take also seroconverted ( kappa =0.779). The level of preexisting antibodies inversely correlated with the rates of clinical take and seroconversion (P

Radiation terrorism--the medical challenge.

Ionizing radiation can cause acute as well as chronic and late illnesses, and is a well-known health hazard. Its use by terrorists and nations in the form of a non-conventional weapon is no longer impossible. The release of radioactive materials with the accompanying contamination and radiation has the potential of causing serious medical problems. In analyzing the different radiologic terrorism scenarios, a scheme is proposed for the triage and evacuation of injured, contaminated and non-contaminated casualties from the scene itself as well as from the periphery. Knowledge, plans and drills will lessen the impact of those potential attacks and prepare us to respond to such events.