Implementation of COVID-19 infection control best practices in nursing homes amid the pandemic.

BACKGROUND: The COVID-19 pandemic has claimed around 170,000 lives among nursing home residents and staff in the United States through April 2023. In a cluster randomized controlled trial (RCT) with 136 nursing homes, we delivered training to improve COVID-19 infection control best practices. We sought to assess the implementation of infection control practices in participating nursing homes. METHODS: Concurrent with the delivery of the RCT (January-November 2021), we surveyed nursing home administrators (NHAs, n = 38) at baseline and 6-month follow-up. Using validated items from the Centers for Disease Control and Prevention (CDC), the surveys inquired about 80 infection control best-practice activities (yes/no). The survey also asked seven scales corresponding to inner setting factors that may have impacted implementation. We assessed changes in infection control practices and inner setting factors between baseline and 6-month follow-up. RESULTS: Overall, the implementation of 11 best practices changed over time. NHAs reported an increase in the availability of informational materials for residents and families (84% vs. 100%, p = 0.031), the use of alcohol-based hand sanitizer over soap (76% vs. 97%, p = 0.008), and the development of contingency plans for increased postmortem care (53% vs. 82%, p = 0.013). The implementation of four best-practice visitation policies and three communal restrictions decreased between baseline and 6-month follow-up (all p < 0.05). Regarding inner setting factors, only culture stress (perceived strain, stress, and role overload) increased between surveys (mean scores: 3.14 vs. 3.58, p = 0.004). CONCLUSION: This study was among the first to report changes in implementing COVID-19 infection control best practices in nursing homes amid the pandemic. Culture stress was an important inner setting factor that may have impacted implementation activities. TRIAL REGISTRATION: NCT04499391 DATE OF REGISTRATION: August 3rd, 2020.

Associations of strabismus surgery timing in childhood with mental health: a retrospective cohort study.

PURPOSE: To investigate the incidence of psychiatric diagnoses in relation to strabismus surgery timing among children with an early strabismus diagnosis who underwent surgery in childhood. METHODS: We conducted a retrospective cohort study using TriNetX network data from 2003-2023 on patients diagnosed with strabismus at ≤5 years of age and having strabismus surgery before 18 years of age. Cohort 1 comprised patients who underwent initial strabismus surgery at ≤6 years of age; cohort 2, patients with initial surgical intervention at ≥7 years of age. Incidence of mental health diagnoses from 7 until 18 years of age were compared between cohorts. RESULTS: In cohort 1, 59 of 688 patients (8.6%) of patients were diagnosed with at least 1 mental health disorder versus 123 of 693 patients (17.7%) in cohort 2 (risk ratio [RR] = 2.07; 95% CI, 1.546 to 2.77; P < 0.0001). Gender analysis showed that only males had a statistically significant increased rate of mental health diagnoses in cohort 2 versus cohort 1 (RR = 1.82; 95% CI, 1.284 to 2.577; P = 0.006). An increased risk for specific psychiatric diagnoses was found in cohort 2 versus cohort 1; anxiety disorders (RR = 2.19; 95% CI, 1.225-3.922; P = 0.0065), attention-deficit / hyperactivity disorder (RR = 2.18; 95% CI, 1.499-3.175; P < 0.0001), conduct disorders (RR = 2.81; 95% CI, 1.425-5.556; P = 0.0018), and adjustment disorders (RR = 2.07; 955% CI, 1.103-3.876; P = 0.0204). Depressive disorders showed no statistically significant difference between cohorts (RR = 1.00; 95% CI, 0.419-2.392; P = 0.9974). CONCLUSIONS: Compared with children having early strabismus surgery, those having surgery at a later age after an early strabismus diagnosis at ≤5 years of age may be more likely to experience a mental health disorder during childhood, although it is unclear whether such disorders are a result of delayed surgery or a driver of the decision to opt for surgery rather than continued conservative management.

Bariatric surgery and COVID-19 outcomes: results from the PaTH to Health: Diabetes study.

BACKGROUND: Obesity and type 2 diabetes mellitus (T2DM) are risk factors for severe COVID-19 infection. Bariatric surgery (BSG) is an effective treatment of obesity through weight loss and may reduce COVID-19 severity. OBJECTIVES: We examined the effect of BSG on COVID-19 outcomes in patients with or at risk of T2DM. SETTING: Electronic health record data from the PaTH Clinical Data Research Network, a partnership of 5 health systems reviewed from March 1, 2020, to December 31, 2020. METHODS: Ambulatory and in-hospital patient encounters with COVID-19 diagnosis and obesity were identified. We constructed 2 patient groups: BSG and non-BSG (NBSG). The BSG group included patients with at least 1 encounter for the BSG procedure code and/or 1 BSG diagnosis code; the NBSG group included patients with no procedure or diagnosis code for BSG with body mass index (BMI) ≥40 or BMI ≥35 and at least 2 obesity-related co-morbidities. We matched 1 patient in the BSG group to 2 patients in the NBSG group based on age, gender (sex defined at birth), race and ethnicity, group (T2DM and at risk of T2DM), and site. The primary outcome was 30-day outcomes of COVID-19 severity. RESULTS: After matching, we found that patients with BSG had lower odds of respiratory failure (41%) and ventilation/intensive care unit (ICU) admission/death (52%). Patients in the BSG group had lower odds of hospitalization, pneumonia, respiratory failure, and the most severe COVID-19 outcomes combined (ventilation/ICU admission/death). T2DM was identified as a risk factor for COVID-19 severity in the BSG group. CONCLUSIONS: This retrospective, matched-cohort analysis found BSG to have a protective effect against severe COVID-19 outcomes.

Neuropathological findings and in vivo imaging correlates of the red nucleus compared to those of the substantia nigra pars compacta in parkinsonisms.

INTRODUCTION: The substantia nigra pars compacta (SNc) is the key pathologic locus in neurodegenerative parkinsonian disorders. Recently, in vivo susceptibility MRI metrics were associated with postmortem glial cell density and tau burden in the SNc of parkinsonism subjects. This study investigated the red nucleus (RN), another iron-rich region adjacent to the SNc and a potential site of higher functionality in parkinsonisms. METHODS: In vivo MRI and postmortem data were obtained from 34 parkinsonism subjects and 3 controls. Neuron density, glial cell density, and percentages of area occupied by α-synuclein and tau were quantified using digitized midbrain slides. R2* and quantitative susceptibility mapping (QSM) metrics in the RN and SNc were derived from multi-gradient echo images. Histopathology data were compared between the RN and SNc using paired t-tests. MRI-histology associations were analyzed using partial Pearson correlations. RESULTS: The RN had greater neuron (t23 = 3.169, P = 0.004) and glial cell densities (t23 = 2.407, P = 0.025) than the SNc, whereas the SNc had greater α-synuclein (t28 = 4.614, P < 0.0001) and tau burden (t24 = 4.513, P = 0.0001). In both the RN (R2*: r = 0.47, P = 0.043; QSM: r = 0.52, P = 0.024) and SNc (R2*: r = 0.57, P = 0.01; QSM: r = 0.58, P = 0.009), MRI values were associated with glial cell density but not neuron density or α-synuclein (Ps > 0.092). QSM associated with tau burden (r = 0.49, P = 0.038) in the SNc, but not the RN. CONCLUSIONS: The RN is resilient to parkinsonian-related pathological processes compared to the SNc, and susceptibility MRI captured glial cell density in both regions. These findings help to further our understanding of the underlying pathophysiological processes in parkinsonisms.

Novel Quality Control Metric for the Pharmacotherapy of Major Depressive Disorder: Measuring Guideline Concordance and Its Impact on Symptom Severity.

Objective: Studies suggest that people with major depressive disorder (MDD) often receive treatment that is not concordant with practice guidelines. To evaluate this, we (1) developed a guideline concordance algorithm for MDD pharmacotherapy (GCA-8), (2) scored it using clinical data, and (3) compared its explanation of patient-reported symptom severity to a traditional concordance measure.Methods: This study evaluated 1,403 adults (67% female, 85% non-Hispanic/Latino White, mean age 43 years) with non-psychotic MDD (per ICD-10 codes), from the Penn State Psychiatry Clinical Assessment and Rating Evaluation System (PCARES) registry (visits from February 1, 2015, to April 13, 2021). We (1) scored 1-year concordance using the Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines and deviation from 8 pharmacotherapy-related criteria and (2) examined associations between concordance and Patient Health Questionnaire depression module (PHQ-9) scores.Results: The mean GCA-8 score was 6.37 (standard deviation [SD] = 1.30; 8.00 = perfect concordance). Among those who switched drugs (n = 671), 81% (n = 542) did not have their dose increased to the recommended maximum before switching. In our adjusted analyses, we found that a 1 SD increase in the GCA-8 was associated with a 0.78 improvement in the mean PHQ-9 score (P < .001). The comparison concordance measure was not associated with the mean PHQ-9 score (ß = -0.20; P = .20; R2 = 0.53), and adding the GCA-8 score significantly improved the model (R2 = 0.54; Vuong test P = .008).Conclusions: By measuring naturalistic MDD pharmacotherapy guideline concordance with the GCA-8, we revealed potential treatment gaps and an inverse association between guideline concordance and MDD symptom severity.

Ecological momentary assessment and cue-elicited drug craving as primary endpoints: study protocol for a randomized, double-blind, placebo-controlled clinical trial testing the efficacy of a GLP-1 receptor agonist in opioid use disorder.

BACKGROUND: Despite continuing advancements in treatments for opioid use disorder (OUD), continued high rates of relapse indicate the need for more effective approaches, including novel pharmacological interventions. Glucagon-like peptide 1 receptor agonists (GLP-1RA) provide a promising avenue as a non-opioid medication for the treatment of OUD. Whereas GLP-1RAs have shown promise as a treatment for alcohol and nicotine use disorders, to date, no controlled clinical trials have been conducted to determine if a GLP-1RA can reduce craving in individuals with OUD. The purpose of the current protocol was to evaluate the potential for a GLP-1RA, liraglutide, to safely and effectively reduce craving in an OUD population in residential treatment. METHOD: This preliminary study was a randomized, double-blinded, placebo-controlled clinical trial designed to test the safety and efficacy of the GLP-1RA, liraglutide, in 40 participants in residential treatment for OUD. Along with taking a range of safety measures, efficacy for cue-induced craving was evaluated prior to (Day 1) and following (Day 19) treatment using a Visual Analogue Scale (VAS) in response to a cue reactivity task during functional near-infrared spectroscopy (fNIRS) and for craving. Efficacy of treatment for ambient craving was assessed using Ecological Momentary Assessment (EMA) prior to (Study Day 1), across (Study Days 2-19), and following (Study Days 20-21) residential treatment. DISCUSSION: This manuscript describes a protocol to collect clinical data on the safety and efficacy of a GLP-1RA, liraglutide, during residential treatment of persons with OUD, laying the groundwork for further evaluation in a larger, outpatient OUD population. Improved understanding of innovative, non-opioid based treatments for OUD will have the potential to inform community-based interventions and health policy, assist physicians and health care professionals in the treatment of persons with OUD, and to support individuals with OUD in their effort to live a healthy life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04199728. Registered 16 December 2019, https://clinicaltrials.gov/study/NCT04199728?term=NCT04199728 . PROTOCOL VERSION: 10 May 2023.

TOPK Inhibition Enhances the Sensitivity of Colorectal Cancer Cells to Radiotherapy by Reducing the DNA Damage Response.

OBJECTIVE: Abnormal expression of T-lymphokine-activated killer cell-originated protein kinase (TOPK) was reported to be closely related to the resistance of prostate cancer to radiotherapy and to targeted drug resistance in lung cancer. However, the role of TOPK inhibition in enhancing radiosensitivity of colorectal cancer (CRC) cells is unclear. This study aimed to evaluate the radiosensitization of TOPK knockdown in CRC cells. METHODS: The expression of TOPK was detected in CRC tissues by immunohistochemistry, and the effect of TOPK knockdown was detected in CRC cells by Western blotting. CCK-8 and clonogenic assays were used to detect the growth and clonogenic ability of CRC cells after TOPK knockdown combined with radiotherapy in CRC cells. Furthermore, proteomic analysis showed that the phosphorylation of TOPK downstream proteins changed after radiotherapy. DNA damage was detected by the comet assay. Changes in the DNA damage response signaling pathway were analyzed by Western blotting, and apoptosis was detected by flow cytometry. RESULTS: The expression of TOPK was significantly greater in CRC tissues at grades 2-4 than in those at grade 1. After irradiation, CRC cells with genetically silenced TOPK had shorter comet tails and reduced expression levels of DNA damage response-associated proteins, including phospho-cyclin-dependent kinase 1 (p-CDK1), phospho-ataxia telangiectasia-mutated (p-ATM), poly ADP-ribose polymerase (PARP), and meiotic recombination 11 homolog 1 (MRE11). CONCLUSIONS: TOPK was overexpressed in patients with moderately to poorly differentiated CRC. Moreover, TOPK knockdown significantly enhanced the radiosensitivity of CRC cells by reducing the DNA damage response.