In their own words: a qualitative survey of healthcare providers' experiences with personal protective equipment during the COVID-19 pandemic.

BACKGROUND: At the beginning of the coronavirus disease (COVID-19) pandemic, healthcare personnel (HCP) faced a dire shortage of personal protective equipment (PPE). This shortage has been identified as a major source of distress among HCP during the early COVID-19 pandemic, though the specific consequences of this shortage have not been identified in the qualitative literature. METHODS: We sought to fill this gap by conducting a qualitative analysis of PPE related free-text comments from online surveys completed by 923 HCP during Spring 2020. RESULTS: We found that HCP used words such as "required" and "had" to describe how their use of non-standard PPE was imposed on them by their workplace, suggesting that they felt little control over their protection at work. HCP described cleaning PPE with novel methods, such as bleach, alcohol, hydrogen peroxide, and UV light, in addition to creating their own PPE out of materials such as garbage bags, sheets, and cloth. Furthermore, HCP expressed frustration with PPE policies at their workplaces, which continued throughout the early pandemic due to the rapidly changing guidelines and the inability to express their opinions to their institutions. The combination of these concerns left HCP scared of being infected with COVID-19 while at work and subsequently infecting their loved ones at home. CONCLUSION: It is critical that healthcare institutions understand HCP's experiences with and feelings towards PPE, as providing the proper protection is vital in ensuring an adequate HCP workforce.

Age-associated accumulation of B cells promotes macrophage inflammation and inhibits lipolysis in adipose tissue during sepsis.

Non-canonical lipolysis induced by inflammatory cytokines or Toll-like receptor ligands is required for the regulation of inflammation during endotoxemia and sepsis. Canonical lipolysis induced by catecholamines declines during aging due to factors including an expansion of lymphocytes, pro-inflammatory macrophage polarization, and an increase in chronic low-grade inflammation; however, the extent to which the non-canonical pathway of lipolysis is active and impacted by immune cells during aging remains unclear. Therefore, we aimed to define the extent to which immune cells from old mice influence non-canonical lipolysis during sepsis. We identified age-associated impairments of non-canonical lipolysis and an accumulation of dysfunctional B1 B cells in the visceral white adipose tissue (vWAT) of old mice. Lifelong deficiency of B cells results in restored non-canonical lipolysis and reductions in pro-inflammatory macrophage populations. Our study suggests that targeting the B cell-macrophage signaling axis may resolve metabolic dysfunction in aged vWAT and attenuate septic severity in older individuals.

Factor VII Deficiency and Second Trimester Abortion: A Case Report.

The prevalence of factor VII deficiency (F7D) is 1 in 500,000. Due to its rarity, the management of bleeding disorders in pregnancy is not well established. We examine a case of an 18-year-old (gravida 1, para 0) woman at approximately 19 weeks gestation with a known history of F7D who presents after a motor vehicle accident. Fetal demise was confirmed necessitating a medical induction. She also had multiple fractures requiring surgical intervention. A multidisciplinary team consisting of orthopedic surgery, obstetrics and gynecology, and hematology/oncology was consulted for optimal timing of factor VII replacement prior to procedures. The patient underwent successful left tibial intramedullary nailing with minimal bleeding. She received factor VII and tolerated an uncomplicated vaginal delivery. Her postpartum and postoperative courses were uncomplicated, requiring one unit of packed red blood cells. The patient was discharged on postpartum day three. Management of this second-trimester abortion with a history of F7D was possible with effective communication and the organization of a multidisciplinary team to account for the risk of thrombosis versus hemorrhage and the availability of factor VII replacement therapy.

Novel Methods for Leveraging Large Cohort Studies for Qualitative and Mixed-Methods Research.

Qualitative research methods, while rising in popularity, are still a relatively underutilized tool in public health research. Usually reserved for small samples, qualitative research techniques have the potential to enhance insights gained from large questionnaires and cohort studies, both deepening the interpretation of quantitative data and generating novel hypotheses that might otherwise be missed by standard approaches; this is especially true where exposures and outcomes are new, understudied, or rapidly changing, as in a pandemic. However, methods for the conduct of qualitative research within large samples are underdeveloped. Here, we describe a novel method of applying qualitative research methods to free-text comments collected in a large epidemiologic questionnaire. Specifically, this method includes: 1) a hierarchical system of coding through content analysis; 2) a qualitative data management application; and 3) an adaptation of Cohen's κ and percent agreement statistics for use by a team of coders, applying multiple codes per record from a large codebook. The methods outlined in this paper may help direct future applications of qualitative and mixed methods within large cohort studies.

Spontaneous Heterotopic Pregnancy: Diagnosis and Management.

Background: Heterotopic pregnancies albeit rare are conceivably life-threatening if missed. With the development of assisted reproductive techniques, the incidence has increased. Confirmation of an intrauterine pregnancy (IUP) should not preclude the existence of a heterotopic pregnancy. Case: A healthy 27-year-old patient (gravida 4, term 1, preterm 0, abortion 2, living 1) at approximately 5 weeks gestation through natural conception presented to the emergency room with acute abdominal pain and vaginal bleeding. Pelvic ultrasound showed evidence of an IUP and a right adnexal mass, raising suspicion for a heterotopic pregnancy. The patient underwent an uncomplicated laparoscopic right salpingectomy. An IUP was confirmed on ultrasound postoperatively. The patient had an early pregnancy loss at 8 weeks of gestation. Conclusion: With a high index of suspicion from clinical presentation and pelvic imaging, heterotopic pregnancy, while rare, should not be ruled out.

A qualitative analysis of psychosocial stressors and health impacts of the COVID-19 pandemic on frontline healthcare personnel in the United States.

There is a dearth of qualitative studies exploring the lived experiences of frontline healthcare personnel (HCP) during the coronavirus disease (COVID-19) pandemic. We examined workplace stressors, psychological manifestations of said stressors, and coping strategies reported through coded open-text responses from 1024 online surveys completed over two months by 923 HCP participating in three nationwide cohorts from Spring 2020. Our findings suggest that risk, job insecurity, frustration with hospital administration, inadequate access to personal protective equipment, and witnessing patient suffering and death contributed to deteriorating mental and physical health. Negative health impacts included the onset or exacerbation of anxiety, depression, and somatic symptoms, including weight fluctuation, fatigue, and migraines. Coping mechanisms included substance use and food consumption, meditation and wellness, fitness, socializing with loved ones, and religious activities. Insights garnered from participants' responses will enable more personalized and effective psychosocial crisis prevention and intervention for frontline HCP in future health crises.

Genome Sequence of CaiB, a DR Cluster Actinobacteriophage That Infects Gordonia rubripertincta.

CaiB is a DR cluster actinobacteriophage that was isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540 as the host. The genome is 61,620 bp, has a GC content of 68.6%, and contains 85 predicted protein coding genes. CaiB has several putative operons and has repeated intergenic regions that may be involved in gene regulation.

Implementation science in adolescent healthcare research: an integrative review.

BACKGROUND: Multiple theories, models and frameworks have been developed to assist implementation of evidence-based practice. However, to date there has been no review of implementation literature specific to adolescent healthcare. This integrative review therefore aimed to determine what implementation science theories, models and frameworks have been applied, what elements of these frameworks have been identified as influential in promoting the implementation and sustainability of service intervention, and to what extent, in what capacity and at what time points has the contribution of adolescent consumer perspectives on evidence implementation been considered.  METHODS: An integrative design was used and reported based on a modified form of the PRISMA (2020) checklist. Seven databases were searched for English language primary research which included any implementation science theory, model or framework developed for/with adolescents or applied in relation to adolescent healthcare services within the past 10 years. Content and thematic analysis were applied with the Consolidated Framework for Implementation Research (CFIR) used to frame analysis of the barriers and facilitators to effective implementation of evidence-informed interventions within youth health settings. RESULTS: From 8717 citations, 13 papers reporting 12 studies were retained. Nine different implementation science theories, frameworks or approaches were applied; six of 12 studies used the CFIR, solely or with other models. All CFIR domains were represented as facilitators and barriers for implementation in included studies. However, there was little or no inclusion of adolescents in the development or review of these initiatives. Only three mentioned youth input, occurring in the pre-implementation or implementation stages. CONCLUSIONS: The few studies found for this review highlight the internationally under-developed nature of this topic. Flagging the importance of the unique characteristics of this particular age group, and of the interventions and strategies to target it, the minimal input of adolescent consumers is cause for concern. Further research is clearly needed and must ensure that youth consumers are engaged from the start and consistently throughout; that their voice is prioritised and not tokenistic; that their contribution is taken seriously. Only then will age-appropriate evidence implementation enable innovations in youth health services to achieve the evidence-based outcomes they offer. TRIAL REGISTRATION: PROSPERO 2020 CRD42020201142 https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=201142.

Ovarian Torsion: Presentation and Management in a Pediatric Patient.

Background: Adnexal torsion is the fifth most common gynecologic emergency accounting for approximately 20 to 30% of ovarian surgeries in pediatric patients. Case: The patient is a ten-year-old female who presented to the emergency room for severe left lower quadrant abdominal pain. On presentation, she was hemodynamically stable with an acute abdomen. A transabdominal ultrasound showed a predominantly anechoic structure measuring up to 5.6 cm without definitive Doppler flow, concerning for a large cyst causing ovarian torsion. Gynecology was consulted, and the patient underwent a diagnostic laparoscopy, aspiration of the left ovarian cyst, and left ovarian detorsion. Pathology results were consistent with benign cystic contents. Conclusion: Appropriate diagnosis and timely surgical gynecological intervention allowed this pediatric patient to salvage and preserve ovarian function.

Survey of Primary Care Provider Comfort in Treating Psychiatric Patients in 2 Community Clinics: A Pilot Study.

Context: Patients with mental health needs are often treated by primary care providers (PCPs). Little is known about current PCP attitudes and comfort level with mental health disorders and treatments despite their role in managing these illnesses.Objective: To quantify PCP comfort with the management of psychiatric disorders and treatments.Methods: PCPs in 2 community clinics were given a survey of psychiatric disorders, treatments, and perceived benefit of assistance from a mental health professional (data were collected during provider meetings in May 2017 and February 2021). Questions were ranked using a Likert scale from 1 to 5 with 1 being "least comfortable," 3 being "neutral," and 5 being "very comfortable." Survey responses about medications and disorders were averaged (ie, mean values were calculated) to approximate PCP comfort with providing psychiatric care with and without support.Results: A total of 71 surveys were sent, and 54 were completed. Overall, respondents indicated comfort greater than neutral in 4 of the 14 disorder-related questions (ie, for anxiety disorders, unipolar depression, attention-deficit/hyperactivity disorder [ADHD], and sleep disorders) and 7 of the 19 treatment-related questions (ie, for selective serotonin reuptake inhibitors [SSRIs]/serotonin-norepinephrine reuptake inhibitors [SNRIs], second-generation antipsychotics, other sleep medications, other antidepressants, stimulants, non-stimulant treatments for ADHD, and tricyclics). SSRIs/SNRIs were the only item with average comfort greater than 4. Mean overall PCP comfort was 2.73 without support. PCP comfort increased significantly with support from a therapist (3.24) or a psychiatrist (4.11) (P < .001), with backup from a psychiatrist providing significantly more comfort than a therapist (P < .001).Discussion: These data show ongoing low comfort levels of PCPs in treating psychiatric conditions, suggesting a need for ongoing educational and collaborative approaches to address this critical unmet need.

Concurrent Paraneoplastic Dermatomyositis and Acquired C1 Esterase Inhibitor Deficiency in Primary Laryngeal Small Cell Carcinoma.

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.

Bioengineered Viral Platform for Intramuscular Passive Vaccine Delivery to Human Skeletal Muscle.

Skeletal muscle is ideal for passive vaccine administration as it is easily accessible by intramuscular injection. Recombinant adeno-associated virus (rAAV) vectors are in consideration for passive vaccination clinical trials for HIV and influenza. However, greater human skeletal muscle transduction is needed for therapeutic efficacy than is possible with existing serotypes. To bioengineer capsids with therapeutic levels of transduction, we utilized a directed evolution approach to screen libraries of shuffled AAV capsids in pools of surgically resected human skeletal muscle cells from five patients. Six rounds of evolution were performed in various muscle cell types, and evolved variants were validated against existing muscle-tropic serotypes rAAV1, 6, and 8. We found that evolved variants NP22 and NP66 had significantly increased primary human and rhesus skeletal muscle fiber transduction from surgical explants ex vivo and in various primary and immortalized myogenic lines in vitro. Importantly, we demonstrated reduced seroreactivity compared to existing serotypes against normal human serum from 50 adult donors. These capsids represent powerful tools for human skeletal muscle expression and secretion of antibodies from passive vaccines.

Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy.

Duchenne muscular dystrophy (DMD) is a rare, muscle degenerative disease resulting from the absence of the dystrophin protein. DMD is characterized by progressive loss of muscle fibers, muscle weakness, and eventually loss of ambulation and premature death. Currently, there is no cure for DMD and improved methods of disease monitoring are crucial for the development of novel treatments. In this study, we describe a new method of assessing disease progression noninvasively in the mdx model of DMD. The reporter mice, which we term the dystrophic Degeneration Reporter strains, contain an inducible CRE-responsive luciferase reporter active in mature myofibers. In these mice, muscle degeneration is reflected in changes in the level of luciferase expression, which can be monitored using noninvasive, bioluminescence imaging. We monitored the natural history and disease progression in these dystrophic report mice and found that decreases in luciferase signals directly correlated with muscle degeneration. We further demonstrated that this reporter strain, as well as a previously reported Regeneration Reporter strain, successfully reveals the effectiveness of a gene therapy treatment following systemic administration of a recombinant adeno-associated virus-6 (rAAV-6) encoding a microdystrophin construct. Our data demonstrate the value of these noninvasive imaging modalities for monitoring disease progression and response to therapy in mouse models of muscular dystrophy.

The protein tyrosine phosphatase 1B inhibitor MSI-1436 stimulates regeneration of heart and multiple other tissues.

Regenerative medicine holds substantial promise for repairing or replacing tissues and organs damaged by disease, injury, and degeneration. Much of the field has focused on development of cell-based therapeutics, gene-based therapeutics, and tissue engineering-based therapeutics. In contrast, development of small molecule regenerative medicine therapies is an emerging area. Using the adult zebrafish as a novel screening platform, we identified MSI-1436 as a first-in-class regenerative medicine drug candidate. MSI-1436 is a naturally occurring aminosterol that inhibits protein tyrosine phosphatase 1B. Treatment of adult zebrafish by intraperitoneal injection of MSI-1436 increased the rate of regeneration of the amputated caudal fin, which is comprised of bone, connective, skin, vascular and nervous tissues and also increased the rate of adult zebrafish heart regeneration. Intraperitoneal administration of MSI-1436 to adult mice for 4 weeks after induction of myocardial infarction increased survival, improved heart function, reduced infarct size, reduced ventricular wall thinning and increased cardiomyocyte proliferation. Satellite cell activation in injured mouse skeletal muscle was stimulated by MSI-1436. MSI-1436 was well tolerated by patients in Phase 1 and 1b obesity and type 2 diabetes clinical trials. Doses effective at stimulating regeneration are 5-50-times lower than the maximum well tolerated human dose. The demonstrated safety and well established pharmacological properties of MSI-1436 underscore the potential of this molecule as a novel treatment for heart attack and multiple other degenerative diseases.