Clinically Suspected Myocarditis Temporally Related to COVID-19 Vaccination in Adolescents and Young Adults: Suspected Myocarditis After COVID-19 Vaccination.

BACKGROUND: Understanding the clinical course and short-term outcomes of suspected myocarditis after the coronavirus disease 2019 (COVID-19) vaccination has important public health implications in the decision to vaccinate youth. METHODS: We retrospectively collected data on patients <21 years old presenting before July 4, 2021, with suspected myocarditis within 30 days of COVID-19 vaccination. Lake Louise criteria were used for cardiac MRI findings. Myocarditis cases were classified as confirmed or probable on the basis of the Centers for Disease Control and Prevention definitions. RESULTS: We report on 139 adolescents and young adults with 140 episodes of suspected myocarditis (49 confirmed, 91 probable) at 26 centers. Most patients were male (n=126, 90.6%) and White (n=92, 66.2%); 29 (20.9%) were Hispanic; and the median age was 15.8 years (range, 12.1-20.3; interquartile range [IQR], 14.5-17.0). Suspected myocarditis occurred in 136 patients (97.8%) after the mRNA vaccine, with 131 (94.2%) after the Pfizer-BioNTech vaccine; 128 (91.4%) occurred after the second dose. Symptoms started at a median of 2 days (range, 0-22; IQR, 1-3) after vaccination. The most common symptom was chest pain (99.3%). Patients were treated with nonsteroidal anti-inflammatory drugs (81.3%), intravenous immunoglobulin (21.6%), glucocorticoids (21.6%), colchicine (7.9%), or no anti-inflammatory therapies (8.6%). Twenty-six patients (18.7%) were in the intensive care unit, 2 were treated with inotropic/vasoactive support, and none required extracorporeal membrane oxygenation or died. Median hospital stay was 2 days (range, 0-10; IQR, 2-3). All patients had elevated troponin I (n=111, 8.12 ng/mL; IQR, 3.50-15.90) or T (n=28, 0.61 ng/mL; IQR, 0.25-1.30); 69.8% had abnormal ECGs and arrhythmias (7 with nonsustained ventricular tachycardia); and 18.7% had left ventricular ejection fraction <55% on echocardiogram. Of 97 patients who underwent cardiac MRI at a median 5 days (range, 0-88; IQR, 3-17) from symptom onset, 75 (77.3%) had abnormal findings: 74 (76.3%) had late gadolinium enhancement, 54 (55.7%) had myocardial edema, and 49 (50.5%) met Lake Louise criteria. Among 26 patients with left ventricular ejection fraction <55% on echocardiogram, all with follow-up had normalized function (n=25). CONCLUSIONS: Most cases of suspected COVID-19 vaccine myocarditis occurring in persons <21 years have a mild clinical course with rapid resolution of symptoms. Abnormal findings on cardiac MRI were frequent. Future studies should evaluate risk factors, mechanisms, and long-term outcomes.

Hypertension after multisystem inflammatory syndrome in children (MIS-C).

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2. Long-term consequences of MIS-C remain unknown. The objective was to describe the prevalence and clinical predictors of hypertension (HTN) and elevated blood pressure (BP) following MIS-C. METHODS: A retrospective study of children ≤ 18 years admitted to a tertiary center with MIS-C was performed. HTN and elevated BP were classified as per the 2017 American Academy of Pediatrics Clinical Practice Guidelines and indexed to the 95th percentile. Data included demographics, inpatient clinical measures, and echocardiograms over 1-year follow-up. Data were analyzed using Kruskal-Wallis, chi-square, and logistic regression. RESULTS: Among 63 children hospitalized with MIS-C (mean age 9.7 ± 4.2 years, 58.7% male, body mass index (BMI) z-score 0.59 ± 1.9), 14% had HTN, and 4% had elevated BP > 30 days post-hospitalization. Multivariate linear regression analysis showed that BMI z-score was significantly associated with higher mean systolic (ß = 2.664, CI = 1.307-3.980, p < 0.001) and diastolic (ß = 2.547, CI = 0.605-4.489, p = 0.012) BP index > 30 days post-hospitalization. Acute kidney injury (AKI) (23.8%) (OR = 2.977, CI = 1.778-4.987, p < 0.001), peak inpatient serum creatinine (OR = 2.524, CI = 1.344-4.740, p = 0.004), and maximum CRP (OR = 1.009, CI = 1.002-1.016, p = 0.014) were all associated with increased odds of post-hospitalization HTN. Left ventricular hypertrophy was present in 46% while hospitalized, compared to 10% at last follow-up. All had return of normal systolic function. CONCLUSIONS: Post-hospitalization HTN and elevated BP may be associated with MIS-C. Children with greater BMI or AKI may be at greater risk for developing HTN after MIS-C. MIS-C follow-up requires careful BP monitoring and antihypertensive medication consideration. A higher resolution version of the Graphical abstract is available as Supplementary information.

What helps people to reduce or stop self-harm? A systematic review and meta-synthesis of first-hand accounts.

BACKGROUND: Self-harm is an important public health problem but therapeutic interventions, particularly for people who have a history of multiple repetition, are not always taken up or effective when they are. The aim of this review is to explore first-hand accounts of what helps outside therapy and identify actions and processes, which can support the reduction or cessation of self-harm. METHODS: A systematic review and thematic meta-synthesis of the first-person accounts of what has helped to reduce or stop self-harm reported in primary studies. RESULTS: The meta-synthesis combined 546 participant excerpts from 56 studies. Two over-arching themes were identified: (i) breaking the chain incorporated actions taken to break the link between a person's current psychological or social state and the act of self-harm and (ii) building a new foundation for change captured actions over the longer-term, focusing on practical changes in relationships and in a person's way of life, such as work or living arrangements. CONCLUSIONS: The results emphasize the importance of interpersonal change in reducing or stopping self-harm. While interpersonal factors are acknowledged as important reasons behind self-harm, they are often under-represented in self-management advice and therapeutic interventions that focus on individual psychopathology.

Barriers and facilitators to accessing and utilising post-treatment psychosocial support by Black men treated for prostate cancer-a systematic review and qualitative synthesis.

PURPOSE: To synthesise findings from published studies on barriers and facilitators to Black men accessing and utilising post-treatment psychosocial support after prostate cancer (CaP) treatment. METHODS: Searches of Medline, Embase, PsycInfo, Cochrane Database of Systematic Reviews and Central, CINAHL plus and Scopus were undertaken from inception to May 2021. English language studies involving Black men aged ≥18 and reporting experiences of, or suggestions for, psychosocial support after CaP treatment were included. Low or moderate quality studies were excluded. Searches identified 4,453 articles and following deduplication, 2,325 were screened for eligibility. Two independent reviewers carried out screening, quality appraisal and data extraction. Data were analysed using thematic synthesis. RESULTS: Ten qualitative studies involving 139 Black men were included. Data analysis identified four analytical constructs: experience of psychosocial support for dealing with treatment side effects (including impact on self-esteem and fear of recurrence); barriers to use of psychosocial support (such as perceptions of masculinity and stigma around sexual dysfunction); facilitators to use of psychosocial support (including the influence of others and self-motivation); and practical solutions for designing and delivering post-treatment psychosocial support (the need for trusted healthcare and cultural channels). CONCLUSIONS: Few intervention studies have focused on behaviours among Black CaP survivors, with existing research predominantly involving Caucasian men. There is a need for a collaborative approach to CaP care that recognises not only medical expertise but also the autonomy of Black men as experts of their illness experience, and the influence of cultural and social networks.

Safety of oral afoxolaner formulated with or without milbemycin oxime in homozygous MDR1-deficient collie dogs.

Afoxolaner, an insecticide and acaricide compound of the isoxazoline class, is available for dogs as an oral ectoparasiticide medicine (NexGard®) and as an oral endectoparasiticide medicine in combination with milbemycin oxime (MO), a macrocyclic lactone (NexGard® Spectra). The safety of these two compounds, alone or in combination, was investigated in homozygous MDR1-deficient collie dogs, in two studies. Overall, 30 adult collie dogs were treated once orally, 9 with a placebo, 9 with afoxolaner, 6 with MO, and 6 with a combination of afoxolaner and MO. For afoxolaner, the mean investigated dosage corresponded to 3.8 and 4.7 multiples of the maximum recommended therapeutic doses (RTD) in NexGard® and NexGard® Spectra, respectively. For MO, the mean investigated dosage corresponded to 4.7 multiples of the maximum RTD in NexGard® Spectra. Dogs were closely monitored for adverse reactions on the day of treatment and for the following two days. No significant adverse reaction was observed in any dog from the afoxolaner or the afoxolaner + MO groups; in the MO-only treated group, mild and transient neurological signs were observed during the 4-8 h post-treatment window. These studies demonstrated a high level of safety of oral afoxolaner, alone or in combination with milbemycin oxime, in homozygous MDR1-deficient dogs.

Acute kidney injury in pediatric patients hospitalized with acute COVID-19 and multisystem inflammatory syndrome in children associated with COVID-19.

This study describes the incidence, associated clinical characteristics and outcomes of acute kidney injury in a pediatric cohort with COVID-19 and Multisystem Inflammatory Syndrome in Children (MIS-C). We performed a retrospective study of patients 18 years of age and under admitted to four New York hospitals in the Northwell Health System interned during the height of the COVID-19 pandemic, between March 9 and August 13, 2020. Acute kidney injury was defined and staged according to Kidney Disease: Improving Global Outcomes criteria. The cohort included 152 patients; 97 acute-COVID-19 and 55 with MIS-C associated with COVID-19. Acute kidney injury occurred in 8 with acute-COVID-19 and in 10 with MIS-C. Acute kidney injury, in unadjusted models, was associated with a lower serum albumin level (odds ratio 0.17; 95% confidence interval 0.07, 0.39) and higher white blood cell counts (odds ratio 1.11; 95% confidence interval 1.04, 1.2). Patients with MIS-C and acute kidney injury had significantly greater rates of systolic dysfunction, compared to those without (80% vs 49%). In unadjusted models, patients with acute kidney injury had 8.4 days longer hospitalizations compared to patients without acute kidney injury (95% confidence interval, 4.4-6.7). Acute kidney injury in acute-COVID-19 and MIS-C may be related to inflammation and/or dehydration. Further research in larger pediatric cohorts is needed to better characterize risk factors for acute kidney injury in acute-COVID-19 and with MIS-C consequent to COVID-19.

Racial and Ethnic Disparities in the Prevalence of Stress and Worry, Mental Health Conditions, and Increased Substance Use Among Adults During the COVID-19 Pandemic - United States, April and May 2020.

In 2019, approximately 51 million U.S. adults aged ≥18 years reported any mental illness,* and 7.7% reported a past-year substance use disorder† (1). Although reported prevalence estimates of certain mental disorders, substance use, or substance use disorders are not generally higher among racial and ethnic minority groups, persons in these groups are often less likely to receive treatment services (1). Persistent systemic social inequities and discrimination related to living conditions and work environments, which contribute to disparities in underlying medical conditions, can further compound health problems faced by members of racial and ethnic minority groups during the coronavirus disease 2019 (COVID-19) pandemic and worsen stress and associated mental health concerns (2,3). In April and May 2020, opt-in Internet panel surveys of English-speaking U.S. adults aged ≥18 years were conducted to assess the prevalence of self-reported mental health conditions and initiation of or increases in substance use to cope with stress, psychosocial stressors, and social determinants of health. Combined prevalence estimates of current depression, initiating or increasing substance use, and suicidal thoughts/ideation were 28.6%, 18.2%, and 8.4%, respectively. Hispanic/Latino (Hispanic) adults reported a higher prevalence of psychosocial stress related to not having enough food or stable housing than did adults in other racial and ethnic groups. These estimates highlight the importance of population-level and tailored interventions for mental health promotion and mental illness prevention, substance use prevention, screening and treatment services, and increased provision of resources to address social determinants of health. How Right Now (Qué Hacer Ahora) is an evidence-based and culturally appropriate communications campaign designed to promote and strengthen the emotional well-being and resiliency of populations adversely affected by COVID-19-related stress, grief, and loss (4).

A Systematic Review of Surface Contamination, Stability, and Disinfection Data on SARS-CoV-2 (Through July 10, 2020).

We conducted a systematic review of hygiene intervention effectiveness against SARS-CoV-2, including developing inclusion criteria, conducting the search, selecting articles for inclusion, and summarizing included articles. Overall, 96 268 articles were screened and 78 articles met inclusion criteria with outcomes in surface contamination, stability, and disinfection. Surface contamination was assessed on 3343 surfaces using presence/absence methods. Laboratories had the highest percent positive surfaces (21%, n = 83), followed by patient-room healthcare facility surfaces (17%, n = 1170), non-COVID-patient-room healthcare facility surfaces (12%, n = 1429), and household surfaces (3%, n = 161). Surface stability was assessed using infectivity, SARS-CoV-2 survived on stainless steel, plastic, and nitrile for half-life 2.3-17.9 h. Half-life decreased with temperature and humidity increases, and was unvaried by surface type. Ten surface disinfection tests with SARS-CoV-2, and 15 tests with surrogates, indicated sunlight, ultraviolet light, ethanol, hydrogen peroxide, and hypochlorite attain 99.9% reduction. Overall there was (1) an inability to align SARS-CoV-2 contaminated surfaces with survivability data and effective surface disinfection methods for these surfaces; (2) a knowledge gap on fomite contribution to SARS-COV-2 transmission; (3) a need for testing method standardization to ensure data comparability; and (4) a need for research on hygiene interventions besides surfaces, particularly handwashing, to continue developing recommendations for interrupting SARS-CoV-2 transmission.

Brucella Exposure Risk Events in 10 Clinical Laboratories, New York City, USA, 2015 to 2017.

From 2015 to 2017, 11 confirmed brucellosis cases were reported in New York City, leading to 10 Brucella exposure risk events (Brucella events) in 7 clinical laboratories (CLs). Most patients had traveled to countries where brucellosis is endemic and presented with histories and findings consistent with brucellosis. CLs were not notified that specimens might yield a hazardous organism, as the clinicians did not consider brucellosis until they were notified that bacteremia with Brucella was suspected. In 3 Brucella events, the CLs did not suspect that slow-growing, small Gram-negative bacteria might be harmful. Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS), which has a limited capacity to identify biological threat agents (BTAs), was used during 4 Brucella events, which accounted for 84% of exposures. In 3 of these incidents, initial staining of liquid media showed Gram-positive rods or cocci, including some cocci in chains, suggesting streptococci. Over 200 occupational exposures occurred when the unknown isolates were manipulated and/or tested on open benches, including by procedures that could generate infectious aerosols. During 3 Brucella events, the CLs examined and/or manipulated isolates in a biological safety cabinet (BSC); in each CL, the CL had previously isolated Brucella Centers for Disease Control and Prevention recommendations to prevent laboratory-acquired brucellosis (LAB) were followed; no seroconversions or LAB cases occurred. Laboratory assessments were conducted after the Brucella events to identify facility-specific risks and mitigations. With increasing MALDI-TOF MS use, CLs are well-advised to adhere strictly to safe work practices, such as handling and manipulating all slow-growing organisms in BSCs and not using MALDI-TOF MS for identification until BTAs have been ruled out.

Loss of myoepithelial calponin-1 characterizes high-risk ductal carcinoma in situ cases, which are further stratified by T cell composition.

A hallmark of ductal carcinoma in situ (DCIS) progression is a loss of the surrounding ductal myoepithelium. However, whether compromise in myoepithelial differentiation, rather than overt cellular loss, can be used to predict the risk of DCIS progression is unknown. Here we address this question utilizing pure and mixed DCIS cases (N = 30) as surrogates for DCIS at low and high risk for progression, respectively. We used multiplex immunohistochemical staining to evaluate the relationship between myoepithelial cell differentiation and lymphoid immune cell types associated with poor prognostic DCIS. Our results show that myoepithelial calponin-1 discriminates between pure and mixed DCIS lesions better than histological subtype, presence of necrosis, or nuclear grade. Additionally, focal loss of myoepithelial cells associated with increased PD-1+CD8+ T cells, which suggests a link between the myoepithelium and immune surveillance. To identify associations between calponin-1 expression and immune response, we performed unsupervised hierarchical clustering of myoepithelial and immune cell biomarkers on 219 DCIS lesions from 30 cases. Notably, the majority of pure (low-risk) DCIS lesions clustered in a high calponin-1, T cell low group, whereas the majority of mixed (high-risk) DCIS lesions clustered in a low calponin-1, T cell high group, specifically with CD8+ and PD-1+CD8+ T cells. However, a subset of pure DCIS lesions had a similar calponin-1 and immune signature as the majority of mixed DCIS lesions, which have low calponin-1 and T cell enrichment-raising the possibility that these pure DCIS lesions might be at a high risk for progression.

Characteristics, Cardiac Involvement, and Outcomes of Multisystem Inflammatory Syndrome of Childhood Associated with severe acute respiratory syndrome coronavirus 2 Infection.

We report on the presentation and course of 33 children with multisystem inflammatory syndrome in children and confirmed severe acute respiratory syndrome coronavirus 2 infection. Hemodynamic instability and cardiac dysfunction were prominent findings, with most patients exhibiting rapid resolution following anti-inflammatory therapy.

Developing and Testing the Detén El Zika Campaign in Puerto Rico.

Responding to an emerging health threat often requires rapid deployment of behavior change communication. Health communication best practices include developing and testing draft messages and materials to ensure that they resonate with and inspire priority groups to act. However, when faced with an emergency health threat, the timeline for these activities can be compressed from months to weeks. This article discusses the rapid development and implementation of a Zika virus prevention campaign for pregnant women in Puerto Rico. The goal of the campaign was to increase knowledge among and motivate pregnant women, their partners and family members, and the community to follow Zika virus prevention recommendations. The steps in campaign development include environmental scanning, concept development and testing, and message testing to ensure development of campaign materials that resonated with and were well-received by key audience groups. The materials adhere to principles of behavior change communication, and offer our insights for development of future campaigns when under time constraints.

Examining the Utility of Coronary Artery Lack of Tapering and Perivascular Brightness in Incomplete Kawasaki Disease.

BACKGROUND: In 2017, the AHA published revised guidelines for the diagnosis of Kawasaki disease (KD). In the absence of compelling data supporting or refuting the utility of lack of tapering (LT) and perivascular brightness (PB), expert panel consensus removed LT and PB from consideration. We hypothesize that LT and PB are unreliable, subjective findings, non-specific to KD, which can be seen in systemic febrile illnesses without KD and in normal controls. METHODS: We performed a single-center retrospective study from 1/2008 to 12/2016. De-identified coronary artery (CA) echocardiographic clips from patients 0-10 years old were interpreted blindly by six pediatric cardiologists. Subjects were grouped as follows: (1) healthy: afebrile with benign murmur, (2) KD: IVIG treatment, 4-5 clinical criteria at presentation, (3) incomplete KD (iKD): IVIG, 1-3 clinical criteria, (4) Febrile: ≥3 days of fever, no IVIG, KD not suspected. The presence or absence of LT and PB was recorded. Inter-rater and intra-rater reliabilities were analyzed using intra-class correlation coefficient, Fleiss' Kappa and Cohen's Kappa coefficients. RESULTS: We interpreted 117 echocardiograms from healthy (27), KD (30), iKD (32), and febrile (28) subjects. Analysis showed moderate agreement in CA z score measurements. LT and PB were observed by most readers in control groups. LT exhibited fair inter-reader agreement (reliability coefficient 0.36) and PB slight inter-reader agreement (reliability coefficient 0.13). Intra-rater reliability was inconsistent for both parameters. CONCLUSIONS: LT and PB are subjective, poorly reproducible features that can be seen in febrile patients without KD and in healthy children.

Strategies to improve recruitment to randomised trials.

BACKGROUND: Recruiting participants to trials can be extremely difficult. Identifying strategies that improve trial recruitment would benefit both trialists and health research. OBJECTIVES: To quantify the effects of strategies for improving recruitment of participants to randomised trials. A secondary objective is to assess the evidence for the effect of the research setting (e.g. primary care versus secondary care) on recruitment. SEARCH METHODS: We searched the Cochrane Methodology Review Group Specialised Register (CMR) in the Cochrane Library (July 2012, searched 11 February 2015); MEDLINE and MEDLINE In Process (OVID) (1946 to 10 February 2015); Embase (OVID) (1996 to 2015 Week 06); Science Citation Index & Social Science Citation Index (ISI) (2009 to 11 February 2015) and ERIC (EBSCO) (2009 to 11 February 2015). SELECTION CRITERIA: Randomised and quasi-randomised trials of methods to increase recruitment to randomised trials. This includes non-healthcare studies and studies recruiting to hypothetical trials. We excluded studies aiming to increase response rates to questionnaires or trial retention and those evaluating incentives and disincentives for clinicians to recruit participants. DATA COLLECTION AND ANALYSIS: We extracted data on: the method evaluated; country in which the study was carried out; nature of the population; nature of the study setting; nature of the study to be recruited into; randomisation or quasi-randomisation method; and numbers and proportions in each intervention group. We used a risk difference to estimate the absolute improvement and the 95% confidence interval (CI) to describe the effect in individual trials. We assessed heterogeneity between trial results. We used GRADE to judge the certainty we had in the evidence coming from each comparison. MAIN RESULTS: We identified 68 eligible trials (24 new to this update) with more than 74,000 participants. There were 63 studies involving interventions aimed directly at trial participants, while five evaluated interventions aimed at people recruiting participants. All studies were in health care.We found 72 comparisons, but just three are supported by high-certainty evidence according to GRADE.1. Open trials rather than blinded, placebo trials. The absolute improvement was 10% (95% CI 7% to 13%).2. Telephone reminders to people who do not respond to a postal invitation. The absolute improvement was 6% (95% CI 3% to 9%). This result applies to trials that have low underlying recruitment. We are less certain for trials that start out with moderately good recruitment (i.e. over 10%).3. Using a particular, bespoke, user-testing approach to develop participant information leaflets. This method involved spending a lot of time working with the target population for recruitment to decide on the content, format and appearance of the participant information leaflet. This made little or no difference to recruitment: absolute improvement was 1% (95% CI -1% to 3%).We had moderate-certainty evidence for eight other comparisons; our confidence was reduced for most of these because the results came from a single study. Three of the methods were changes to trial management, three were changes to how potential participants received information, one was aimed at recruiters, and the last was a test of financial incentives. All of these comparisons would benefit from other researchers replicating the evaluation. There were no evaluations in paediatric trials.We had much less confidence in the other 61 comparisons because the studies had design flaws, were single studies, had very uncertain results or were hypothetical (mock) trials rather than real ones. AUTHORS' CONCLUSIONS: The literature on interventions to improve recruitment to trials has plenty of variety but little depth. Only 3 of 72 comparisons are supported by high-certainty evidence according to GRADE: having an open trial and using telephone reminders to non-responders to postal interventions both increase recruitment; a specialised way of developing participant information leaflets had little or no effect. The methodology research community should improve the evidence base by replicating evaluations of existing strategies, rather than developing and testing new ones.

Validation of droplet digital PCR for the detection and absolute quantification of Borrelia DNA in Ixodes scapularis ticks.

We evaluated the QX200 Droplet Digital PCR (ddPCR™, Bio-Rad) system and protocols for the detection of the tick-borne pathogens Borrelia burgdorferi and Borrelia miyamotoi in Ixodes scapularis nymphs and adults collected from North Truro, Massachusetts. Preliminary screening by nested PCR determined positive infection levels of 60% for B. burgdorferi in these ticks. To investigate the utility of ddPCR as a screening tool and to calculate the absolute number of bacterial genome copies in an infected tick, we adapted previously reported TaqMan®-based qPCR assays for ddPCR. ddPCR proved to be a reliable means for detection and absolute quantification of control bacterial DNA with precision as low as ten spirochetes in an individual sample. Application of this method revealed the average carriage level of B. burgdorferi in infected I. scapularis nymphs to be 2291 spirochetes per nymph (range: 230-5268 spirochetes) and 51 179 spirochetes on average in infected adults (range: 5647-115 797). No ticks naturally infected with B. miyamotoi were detected. The ddPCR protocols were at least as sensitive to conventional qPCR assays but required fewer overall reactions and are potentially less subject to inhibition. Moreover, the approach can provide insight on carriage levels of parasites within vectors.

Frequency and Distribution of Rickettsiae, Borreliae, and Ehrlichiae Detected in Human-Parasitizing Ticks, Texas, USA.

To describe the presence and distribution of tickborne bacteria and their vectors in Texas, USA, we screened ticks collected from humans during 2008-2014 for Rickettsia, Borrelia, and Ehrlichia spp. Thirteen tick species were identified, and 23% of ticks carried bacterial DNA from at least 1 of the 3 genera tested.

Predictors of anxiety and depression in people with colorectal cancer.

BACKGROUND: People living with colorectal cancer are at risk of anxiety and depression. We investigated what factors were most highly associated with these. METHODS: Four hundred and ninety-six people with colorectal cancer completed the Hospital Anxiety and Depression Scale (HADS). Data on functioning, symptoms, illness perceptions and social difficulties were collected by questionnaire. Case-note-identified disease, treatment and co-morbidity data were recorded. Multiple logistic regression identified factors independently predictive of anxiety and depression caseness. RESULTS: Self-reported history of anxiety/depression predicted anxiety but not depression caseness. Depression caseness predicted anxiety caseness (p = 0.043), as did poorer self-reported cognitive functioning (p = 0.001), dyspnoea (p = 0.015) or diarrhoea (p = 0.021), reporting a high negative life and emotional impact (p < 0.001) and having difficulties with finance (p = 0.007). Having neo-adjuvant radiotherapy increased the odds of depression caseness (p = 0.007), as did poorer physical (p = 0.007), cognitive (p < 0.001) and social (p < 0.001) functioning, having constipation (p = 0.011), reporting a high negative life and emotional impact (p < 0.001), having difficulties with personal care (p = 0.022) and communicating with others (p = 0.014). CONCLUSION: Levels of anxiety caseness were similar to those of non-clinical samples, but depression caseness was higher, particularly in those who had received neo-adjuvant radiotherapy. Most factors associated with possible or probable depression may be modified with appropriate intervention.

Efficacy of moxidectin, using various dose regimens, against JYD-34, a macrocyclic lactone resistant isolate of Dirofilaria immitis.

BACKGROUND: Macrocyclic lactones (MLs) are the only class of drugs currently commercially available that are effective for preventing heartworm disease. The data presented in this article provide information on the efficacy of oral moxidectin against JYD-34, a known ML-resistant Dirofilaria immitis isolate, when dogs are treated under various dosing regimens. METHODS: Fifty-two purpose-bred Beagle dogs were used in five laboratory studies. All dogs were inoculated with 50 D. immitis third-stage larvae (L3) (JYD-34 isolate) 30 days prior to the first treatment. Dogs were randomized to treatment (four to five animals in each group) with one, three, or five monthly doses of oral moxidectin ranging from 6 to 100 µg/kg body weight. In each study, control dogs were not treated. Five to 6 months after L3 inoculation, dogs were euthanized, and adult worms were counted to evaluate efficacy of the dosing regimens. RESULTS: Adult heartworms were recovered from all control dogs, with an overall geometric mean of 29.7 worms (range 15.2 to 38.0, individual counts ranged from 8 to 51). Five monthly doses of 6 µg/kg provided 83.3% and 90.2%, efficacy, and the same number of monthly doses of 9 µg/kg demonstrated 98.8% and 94.1% efficacy. Three monthly doses of 30 and 50 µg/kg demonstrated 97.9% and 99.0% efficacy, respectively, while a single dose of 100 µg/kg demonstrated 91.1% efficacy. CONCLUSIONS: Five monthly doses of 9 µg/kg provided similar or only marginally lower efficacy against JYD-34, a known ML-resistant isolate, compared to substantially higher doses administered for 3 months. This underscores the importance of duration of exposure to moxidectin when facing ML-resistant isolates. Repeated administration of lower doses of moxidectin are an alternative to higher doses in the prevention of heartworm disease associated with less susceptible or resistant isolates.

Safety of an oral combination of moxidectin, afoxolaner, and pyrantel pamoate in dogs.

NexGard®PLUS (moxidectin, afoxolaner, and pyrantel pamoate), is an oral combination product for dogs indicated for the prevention of heartworm disease, the treatment and prevention of flea and tick infestations, and the treatment of gastro-intestinal nematode infections. The safety of this product in dogs was evaluated in three studies. Study #1 was a margin-of-safety study conducted in puppies, dosed six times at 28-day intervals at 1X, 3X, or 5X multiples of the maximum exposure dose (equivalent to 24 µg/kg moxidectin, 5 mg/kg afoxolaner, and 10 mg/kg pyrantel). In Study #2, the product was administered to ABCB1-deficient collie dogs at a 1X dose twice at a 28-day interval, and at a 3X or 5X dose once. Study #3 evaluated the safety of the product at 1X and 3X doses administered three times at 4-week intervals, to dogs harboring adult Dirofilaria immitis. In the three studies, the safety was evaluated on the basis of multiple clinical observations and physical examinations, including a complete assessment of toxicity to macrocyclic lactones, and on comprehensive clinical and anatomical pathology evaluations in Study #1. No clinically significant combination product-related effects were observed in any of the three studies. No signs of macrocyclic lactone toxicity were observed in the ABCB1-deficient collie dogs. Some mild and self-resolving instances of emesis or diarrhea were occasionally observed in the 3X and 5X dosed dogs. NexGard® PLUS was demonstrated to be safe following multiple administrations in puppies, in ABCB1-deficient collie dogs, and in microfilaremic dogs infected with adult D. immitis.

Early Treatment of Multisystem Inflammatory Syndrome in Children.

BACKGROUND AND OBJECTIVES: Multisystem inflammatory syndrome in children (MIS-C) is a severe hyperinflammatory illness occurring after severe acute respiratory syndrome coronavirus 2 infection. The optimal treatment of MIS-C is unknown, although prior studies have indicated benefits of intravenous immunoglobulin (IVIG) and glucocorticoids. We hypothesize that early treatment with glucocorticoids is associated with shorter hospital length of stay (LOS). METHODS: This study is a multicenter retrospective cohort study of patients hospitalized with MIS-C over a roughly 1-year period. The primary outcome was hospital LOS comparing subjects who received glucocorticoids within 48 hours of arrival to the treating hospital to those who did not. Secondary outcomes included ICU LOS. Unadjusted and adjusted analyses were performed. RESULTS: The final analysis included 131 subjects. Subjects who received early glucocorticoids were more likely to receive early IVIG and to require ICU admission. Early glucocorticoid administration was associated with shorter ICU LOS (4 vs 9 days, P = .004) in the unadjusted analysis. In the adjusted analysis, early glucocorticoid administration and early IVIG administration were both independently associated with shorter hospital LOS (incidence rate ratio 0.75, P = .025; incidence rate ratio 0.56, P = .026, respectively). CONCLUSIONS: Glucocorticoids and intravenous immunoglobulin were independently associated with shorter hospital length of stay when given early in hospitalization to MIS-C patients after accounting for potential confounding factors. The optimal dose and duration of treatment require further investigation, but this study supports early combination therapy with both IVIG and glucocorticoids for all children hospitalized with MIS-C.