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Background Influenza may be associated with increased stroke and myocardial infarction (MI) risk. We hypothesized that risk of stroke and MI after influenza-like illness (ILI) would be higher in patients in New York State. We additionally assessed whether this relationship differed across a series of sociodemographic factors. Methods A case-crossover analysis of the 2012–2014 New York Statewide Planning and Research Cooperative System (SPARCS) was used to estimate odds of ischemic stroke and MI after ILI. Each patient’s case window (the time period preceding event) was compared to their control windows (same dates from the previous 2 years) in conditional logistic regression models used to estimate odds ratios and 95% confidence intervals (OR, 95% CI). We varied the case windows from 15 to 365 days preceding event as compared to control windows constructed using the same dates from the previous 2 years. Analyses were stratified by sex, race, and urban-rural status based on residential zip code. Results A total of 33,742 patients were identified as having ischemic stroke and 53,094 had MI. ILI events in the 15 days prior were associated with a 39% increase in odds of ischemic stroke (95% CI 1.09–1.77), increasing to an almost 70% increase in odds when looking at ILI events over the last year (95% CI 1.56, 1.83). In contrast, the effect of ILI hospitalization on MI was strongest in the 15 days prior (OR = 1.24, 95% CI 1.06–1.44). The risk of ischemic stroke after ILI was higher among individuals living in rural areas in the 90 days prior to stroke and among men in the year prior to event. In contrast, the association between ILI and MI varied only across race with whites having significantly higher ILI associated MI. Conclusion This study highlights risk period differences for acute cardiovascular events after ILI, indicating possible differences in mechanism behind the risk of stroke after ILI compared to the risk of MI. High risk populations for stroke after ILI include men and people living in rural areas, while whites are at high risk for MI after ILI. Future studies are needed to identify ways to mitigate these risks.

As of October 28, 2022, a total of 28,244* monkeypox (mpox) cases have been reported in the United States during an outbreak that has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (1). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series (with doses administered 4 weeks apart), was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and mpox disease (2); an FDA Emergency Use Authorization issued on August 9, 2022, authorized intradermal administration of 0.1 mL per dose, increasing the number of persons who could be vaccinated with the available vaccine supply (3). A previous comparison of mpox incidence during July 31-September 3, 2022, among unvaccinated, but vaccine-eligible men aged 18-49 years and those who had received ≥1 JYNNEOS vaccine dose in 32 U.S. jurisdictions, found that incidence among unvaccinated persons was 14 times that among vaccinated persons (95% CI = 5.0-41.0) (4). During September 4-October 1, 2022, a total of 205,504 persons received JYNNEOS vaccine dose 2 in the United States. To further examine mpox incidence among persons who were unvaccinated and those who had received either 1 or 2 JYNNEOS doses, investigators analyzed data on 9,544 reported mpox cases among men aged 18-49 years during July 31-October 1, 2022, from 43 U.S. jurisdictions,** by vaccination status. During this study period, mpox incidence (cases per 100,000 population at risk) among unvaccinated persons was 7.4 (95% CI = 6.0-9.1) times that among persons who received only 1 dose of JYNNEOS vaccine ≥14 days earlier and 9.6 (95% CI = 6.9-13.2) times that among persons who received dose 2 ≥14 days earlier. The observed distribution of subcutaneous and intradermal routes of administration of dose 1 among vaccinated persons with mpox was not different from the expected distribution. This report provides additional data suggesting JYNNEOS vaccine provides protection against mpox, irrespective of whether the vaccine is administered intradermally or subcutaneously. The degree and durability of such protection remains unclear. Persons eligible for mpox vaccination should receive the complete 2-dose series to optimize strength of protection (5).

Human monkeypox is caused by Monkeypox virus (MPXV), an Orthopoxvirus, previously rare in the United States (1). The first U.S. case of monkeypox during the current outbreak was identified on May 17, 2022 (2). As of September 28, 2022, a total of 25,341 monkeypox cases have been reported in the United States.* The outbreak has disproportionately affected gay, bisexual, and other men who have sex with men (MSM) (3). JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic), administered subcutaneously as a 2-dose (0.5 mL per dose) series with doses administered 4 weeks apart, was approved by the Food and Drug Administration (FDA) in 2019 to prevent smallpox and monkeypox infection (4). U.S. distribution of JYNNEOS vaccine as postexposure prophylaxis (PEP) for persons with known exposures to MPXV began in May 2022. A U.S. national vaccination strategy for expanded PEP, announced on June 28, 2022, recommended subcutaneous vaccination of persons with known or presumed exposure to MPXV, broadening vaccination eligibility. FDA emergency use authorization (EUA) of intradermal administration of 0.1 mL of JYNNEOS on August 9, 2022, increased vaccine supply (5). As of September 28, 2022, most vaccine has been administered as PEP or expanded PEP. Because of the limited amount of time that has elapsed since administration of initial vaccine doses, as of September 28, 2022, relatively few persons in the current outbreak have completed the recommended 2-dose series. To examine the incidence of monkeypox among persons who were unvaccinated and those who had received ≥1 JYNNEOS vaccine dose, 5,402 reported monkeypox cases occurring among males aged 18-49 years during July 31-September 3, 2022, were analyzed by vaccination status across 32 U.S. jurisdictions.** Average monkeypox incidence (cases per 100,000) among unvaccinated persons was 14.3 (95% CI = 5.0-41.0) times that among persons who received 1 dose of JYNNEOS vaccine ≥14 days earlier. Monitoring monkeypox incidence by vaccination status in timely surveillance data might provide early indications of vaccine-related protection that can be confirmed through other well-controlled vaccine effectiveness studies. This early finding suggests that a single dose of JYNNEOS vaccine provides some protection against monkeypox infection. The degree and durability of such protection is unknown, and it is recommended that people who are eligible for monkeypox vaccination receive the complete 2-dose series.

Frozen stuffed breaded raw chicken products have repeatedly been implicated in Salmonella outbreaks (1). These products are partially cooked to set the breading, often making them appear cooked (2). Despite their appearance, these products need to be cooked to an internal temperature of 165°F (74°C) to ensure that they are safe to eat. Producers began implementing labeling changes in 2006 to more clearly identify these products as raw; many warn against using microwave ovens (microwaves) to prepare them and provide validated cooking instructions solely for conventional ovens (ovens) (3,4). However, outbreaks continued to occur after implementation of these labeling changes (4). To describe the demographic characteristics of persons who prepare frozen stuffed chicken products and which appliances they use to prepare them, data from a May-July 2022 representative panel survey were analyzed. Although most (82.7%) respondents used an oven as one of their cooking methods, more than one half (54.0%) of respondents also used another appliance, including 29.0% who used a microwave. Oven use was lower among respondents with household income <$25,000 (68.9%), and who lived in mobile homes or other portable types of homes (66.5%). Among respondents who reported using microwaves to cook these products, 8% reported using a microwave with ≤750 W of power, which might be insufficient to thoroughly cook such products (1,5,6). Economic and other factors might influence some groups' access to recommended cooking appliances. Companies could consider implementing additional interventions that rely less on labeling and consumer preparation practices and focus on controlling or reducing levels of Salmonella in these products, such as selling them fully cooked, or monitoring and testing Salmonella levels, to ensure safety. These findings highlight challenges consumers might face in preparing frozen stuffed chicken products safely and can guide strategies for regulatory authorities and industry to prevent outbreaks and illnesses associated with them.

As of November 14, 2022, monkeypox (mpox) cases had been reported from more than 110 countries, including 29,133 cases in the United States.* Among U.S. cases to date, 95% have occurred among males (1). After the first confirmed U.S. mpox case on May 17, 2022, limited supplies of JYNNEOS vaccine (Modified Vaccinia Ankara vaccine, Bavarian Nordic) were made available to jurisdictions for persons exposed to mpox. JYNNEOS vaccine was approved by the Food and Drug Administration (FDA) in 2019 as a 2-dose series (0.5 mL per dose, administered subcutaneously) to prevent smallpox and mpox disease. On August 9, 2022, FDA issued an emergency use authorization to allow administration of JYNNEOS vaccine by intradermal injection (0.1 mL per dose) (2). A previous report on U.S. mpox cases during July 31-September 3, 2022, suggested that 1 dose of vaccine offers some protection against mpox (3). This report describes demographic and clinical characteristics of cases occurring ≥14 days after receipt of 1 dose of JYNNEOS vaccine and compares them with characteristics of cases among unvaccinated persons with mpox and with the vaccine-eligible vaccinated population in participating jurisdictions. During May 22-September 3, 2022, among 14,504 mpox cases reported from 29 participating U.S. jurisdictions, 6,605 (45.5%) had available vaccination information and were included in the analysis. Among included cases, 276 (4.2%) were among persons who had received 1 dose of vaccine ≥14 days before illness onset. Mpox cases that occurred in these vaccinated persons were associated with lower percentage of hospitalization (2.1% versus 7.5%), fever, headache, malaise, myalgia, and chills, compared with cases in unvaccinated persons. Although 1 dose of JYNNEOS vaccine offers some protection from disease, mpox infection can occur after receipt of 1 dose, and the duration of protection conferred by 1 dose is unknown. Providers and public health officials should therefore encourage persons at risk for acquiring mpox to complete the 2-dose vaccination series and provide guidance and education regarding nonvaccine-related prevention strategies (4).

Gaeumannomyces tritici is responsible for take-all disease, one of the most important wheat root threats worldwide. High-quality annotated genome resources are sorely lacking for this pathogen, as well as for the closely related antagonist and potential wheat take-all biocontrol agent, G. hyphopodioides . As such, we know very little about the genetic basis of the interactions in this host–pathogen–antagonist system. Using PacBio HiFi sequencing technology we have generated nine near-complete assemblies, including two different virulence lineages for G. tritici and the first assemblies for G. hyphopodioides and G. avenae (oat take-all). Genomic signatures support the presence of two distinct virulence lineages in G. tritici (types A and B), with A strains potentially employing a mechanism to prevent gene copy-number expansions. The CAZyme repertoire was highly conserved across Gaeumannomyces , while candidate secreted effector proteins and biosynthetic gene clusters showed more variability and may distinguish pathogenic and non-pathogenic lineages. A transition from self-sterility (heterothallism) to self-fertility (homothallism) may also be a key innovation implicated in lifestyle. We did not find evidence for transposable element and effector gene compartmentalisation in the genus, however the presence of Starship giant transposable elements may contribute to genomic plasticity in the genus. Our results depict Gaeumannomyces as an ideal system to explore interactions within the rhizosphere, the nuances of intraspecific virulence, interspecific antagonism, and fungal lifestyle evolution. The foundational genomic resources provided here will enable the development of diagnostics and surveillance of understudied but agriculturally important fungal pathogens.

IntroductionCrotalidae immune F(ab’)2 (Fab2AV) became available in the USA in 2019 for treatment of rattlesnake envenomation. In the clinical trial comparing Fab2AV to crotalidae immune polyvalent fab (FabAV), Fab2AV was associated with less late hemotoxicity. The purpose of this study was to describe outcomes following use of Fab2AV in patients with rattlesnake envenomation in Arizona.MethodsThis is an observational study of patients admitted to a medical toxicology service at two hospitals in Arizona between January 1, 2019 and December 31, 2020. Patients with rattlesnake envenomation who received Fab2AV were included. Patients who received FabAV, alone or in combination with Fab2AV, were excluded. The main outcomes of interest were antivenom dose, adverse reactions, late hemotoxicity, and hospital readmission or retreatment.ResultsForty-six patients were included. The mean age was 40 years, with 15% under 12 years of age. All exhibited swelling, 20% thrombocytopenia, and 35% coagulopathy. Median time to treatment was 3 h and median total Fab2AV dose was 20 vials. Three patients had an acute reaction to Fab2AV which was non-life-threatening and resolved with antihistamines and/or steroids. In the follow-up period, one case of delayed thrombocytopenia (platelets = 108 K/mm3) and one case of recurrent thrombocytopenia (platelets = 111 K/mm3) were identified. There was no late coagulopathy. Five patients reported symptoms consistent with mild serum sickness.ConclusionsIn this series of patients with rattlesnake envenomation in Arizona who were treated with Fab2AV, there were no cases of clinically significant late hemotoxicity, and no patients required late retreatment with antivenom. Acute and delayed reactions did occur in some patients but were mild and easily treated.

IntroductionMeasurement of serum acetaminophen-protein adducts (APAP-CYS) has been suggested to support or refute a diagnosis of acetaminophen (APAP)-induced hepatotoxicity when ingestion histories are unreliable or unavailable and when circulating APAP concentrations are low or undetectable. Non-APAP overdose patients commonly have used APAP products in non-toxic quantities and, thus, will have measurable APAP-CYS concentrations, even when hepatic injury results from other causes, such as ischemic hepatitis. The relationship between alanine aminotransferase (ALT) activity and APAP-CYS concentration might assist in distinguishing between toxic and non-toxic APAP doses in patients suspected of drug overdose.MethodsWe measured serial levels of serum APAP-CYS and ALT activities in 500 overdose patients in whom APAP toxicity was suspected on inpatient admission, but who were then classified at time of discharge and before results of APAP-CYS concentrations were available into three groups: 1) definite APAP group; 2) definitely not APAP group; and 3) indeterminate group. Subjects in the definite and definitely not APAP groups were selected in whom a plasma ALT activity was measured within ± 4 h of a serum APAP-CYS concentration. Regressions with correlation coefficients between APAP-CYS and ALT were calculated for repeat measures in the 335 subjects (908 blood samples) in the definite APAP group and 79 subjects (231 samples) in the definitely not APAP group, with an emphasis on APAP-CYS concentrations and calculation of 95% prediction intervals when ALT was ≥ 1000 IU/L.ResultsA strong correlation was found between APAP-CYS and ALT in the definite APAP group over all ALT activities (r = 0.93, p < 0.001; N = 335), and when ALT was > 1000 IU/L (r = 0.82, p < 0.001, N = 144). In the 79 definitely not APAP subjects, no significant correlation was found when ALT exceeded 1000 IU/L (r = 0.04; p = 0.84, N = 32). All subjects in the definitely not APAP group displayed APAP-CYS concentrations < 3 μM. In definitely not APAP subjects, the great majority of APAP-CYS levels were below the 95% prediction interval for APAP-CYS concentrations in definite APAP group subjects when ALT was ≥ 1000 IU/L. However, some definitely not APAP group subjects who had ingested non-toxic doses of APAP displayed APAP-CYS concentrations as high as 2.8 μM in the face of ALT elevation from ischemic hepatitis.ConclusionThe interpretation of serum APAP-CYS concentrations must always be made in light of detailed clinical information and the population being tested, especially because of some overlap in APAP-CYS levels in subjects with and without APAP toxicity.

Objectives. To evaluate the validity of patient report, pharmacy dispensing records, and pill counts as measures of antihypertensive adherence using electronic monitoring as the validation standard. Methods. The study was conducted among 286 members of Harvard Pilgrim Health Care, a managed care organization, who were at least 18 years of age, on monotherapy for hypertension, and had prescription drug coverage. Prescription refill adherence during the 12 months before enrollment was determined from their automated pharmacy dispensing records. Participants were interviewed about their medication adherence before and after a 3-month electronic monitoring period during which pill counts were also performed. Adherence to both recommended number and timing of doses was estimated from electronic monitoring data. Data analysis was based on statistical correlation and analysis of variance. Results. Electronic adherence monitoring revealed that the proportion of prescribed doses consumed was higher (0.92) than the proportion of doses taken on time (0.63). The correlation between adherence to quantity and timing of doses was 0.32. Concurrent pill counts and earlier refilling patterns were moderately correlated with electronic monitoring (pill count: r = .52 with quantity and r = .17 with timing; refill adherence r = .32 with quantity and r = .22 with timing). There was considerable misclassification of adherence reported by patients, although nonadherence was generally accurately reported. Conclusions. Deviation from recommended timing of doses appears to be greater than from prescribed number of doses. Pharmacy dispensing records demonstrate predictive validity as measures of cumulative exposure and gaps in medication supply. Adherence levels determined from pill counts and pharmacy dispensing records correlate more closely with quantity than with timing of doses. Nonadherence reported by patients can serve as a qualitative indicator and predictor of reduced adherence.

Since 2010, the American College of Medical Toxicology (ACMT) Toxicology Investigators Consortium (ToxIC) has maintained the ToxIC Core Registry, a national case registry of in-hospital and clinic patient consultations submitted by medical toxicology physicians. Deidentified patient data entered into the registry includes patient demographics, reason for medical toxicology evaluation, exposure agents, clinical signs and symptoms, treatments and antidotes administered, and mortality. This fourteenth annual report provides data from 7392 patients entered into the Core Registry in 2023 by 36 participating sites comprising 61 distinct healthcare facilities, bringing the total case count to 102331 between 2010 and 2023. Ethanol was the most commonly reported exposure agent class (24.4%), followed by opioids (22.7%), non-opioid analgesics (16.7%), and antidepressants (11.7%). For the first time since the registry’s initiation, in 2023, ethanol was the leading agent of exposure. There were 98 fatalities (case fatality rate of 1.3%). Additional descriptive analyses in this annual report were conducted to describe the reasons for medical toxicology consultation by age in 2023, and yearly trends for opioid and psychoactive exposures, physostigmine and rivastigmine treatments, and acetaminophen exposures treated with fomepizole.