Objective To describe post-traumatic stress disorder (PTSD)-related symptoms and frequent psychiatric comorbidities, treatments received, healthcare resource utilization (HRU), and healthcare costs pre- and post-PTSD diagnosis among adults in the United States. Methods Adults with PTSD who received a PTSD-related pharmacological treatment (selective serotonin reuptake inhibitor [SSRI], serotonin-norepinephrine reuptake inhibitor [SNRI], atypical antipsychotic [AA]) within 24 months of the first observed PTSD diagnosis (index date) were identified using MarketScan Commercial Database (2015–2020). Study outcomes were assessed during the 6-month pre-diagnosis and 24-month post-diagnosis periods. Subgroup analyses included patients treated or not treated with AAs post-PTSD diagnosis. Results Of the overall patients (N = 26,306; mean age at diagnosis 39.5 years; 73.3% female), 85.9% had PTSD-related symptoms and frequent psychiatric comorbidities during the 6 months pre-diagnosis. Patients treated with AAs post-PTSD diagnosis (N = 9,298) tended to have higher rates of PTSD-related symptoms and comorbidities at diagnosis than those not treated with AAs (N = 7,011). Following diagnosis, the most commonly observed first-line treatments were SSRI (67.4%), AA (23.4%), and SNRI (22.6%). The rate of PTSD-related symptoms and comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs increased during the 6 months post-diagnosis relative to the 6 months pre-diagnosis and then declined over time during the 24 months post-diagnosis. Conclusions The PTSD diagnosis was associated with increased rates of symptoms and frequent psychiatric comorbidities, psychotherapy and pharmacological treatments received, HRU, and healthcare costs, pointing to increased patient monitoring. Within 6 to 12 months after the PTSD diagnosis, these outcomes tended to reduce, perhaps as patients were obtaining targeted and effective care.

Objective The use of herbal products/dietary supplements (HP/DS) in endocrinal chronic diseases is growing. However, no studies have evaluated their use in patients who present to endocrinology and metabolic diseases clinics. This descriptive study aims to investigate the rate of HP/DS use and the factors affecting this in patients who presented to Karadeniz Technical University (KTU) Farabi Hospital Endocrinology and Metabolic Diseases Clinic, Türkiye between 01.11.2021 and 01.05.2022. Methods Five hundred six questionnaires with acceptable data quality were included this investigation. The data were analyzed on SPSS version 23.0 software. The factors with the greatest effect on the use of HP/DS were determined using binary logistic regression analysis. Results Analysis showed that 49.4% of the participants used HP/DS. The main factors affecting the use of herbal products were age, diagnosis of the disease, and treatment compliance problems. The most frequently used products were lemon, cinnamon, black cumin, ginger, turmeric, and dill. The participants main sources of information about HP/DS were friends/relatives, the internet/social media, and television, respectively. 74.8% of the participants using HP/DS did not inform their physcisian/pharmacist about such use, although 81.8% of these nevertheless wished to receive information from these occupational groups. Conclusion Herbal product monitoring in patients should be performed in collaboration with pharmacists, herbal product use should be investigated, and counseling services should be made available in order to maintain and promote public health.

Objective Many models for predicting various disease prognoses have achieved high performance without laboratory test results. However, whether laboratory test results can improve performance remains unclear. This study aimed to investigate whether laboratory test results improve the model performance for coronavirus disease 2019 (COVID-19). Methods Prediction models were developed using data from the electronic healthcare record database in Japan. Patients aged ≥ 18 years hospitalized for COVID-19 after February 11, 2020, were included. Their age, sex, comorbidities, laboratory test results, and number of days from February 11, 2020, were collected. We developed a logistic regression, XGBOOST, random forest, and neural network analysis and compared the performance with and without laboratory test results. The performance of predicting in-hospital death was evaluated using the area under the curve (AUC). Results Data from 8,288 hospitalized patients (females, 46.5%) were analyzed. The median patient age was 71 years. A total of 6,630 patients were included in the training dataset, and 312 (4.7%) died. In the logistic regression model, the area under the curve was 0.88 (95% confidence interval [CI]:0.83–0.93) and 0.75 (95% CI: 0.68–0.81) with and without laboratory test results, respectively. The performance was not fundamentally different between the model types, and the laboratory test results improved the performance in all cases. The variables useful for prediction were blood urea nitrogen, albumin, and lactate dehydrogenase. Conclusions Laboratory test results, such as blood urea nitrogen, albumin, and lactate dehydrogenase levels, along with background information, helped estimate the prognosis of patients hospitalized for COVID-19.

Objectives Insulin resistance (IR) is a significant metabolic disturbance that plays a pivotal role in various health conditions, including hypothyroidism. Homeostatic Model Assessment For İnsulin Resistance (HOMA-IR) is widely used for assessing IR. However, alternative indices, such as the Metabolic Score for Insulin Resistance (METS-IR), have been developed for diverse applications. This study aimed to meticulously investigate IR in patients with hypothyroidism and to compare the effectiveness of METS-IR with HOMA-IR. To enrich our analyses, additional metrics, including the Triglyceride Glucose (TyG) Index, the Triglyceride to High-Density Lipoprotein Cholesterol Ratio (TG/HDL-C), and the Quantitative Insulin Sensitivity Check Index (QUICKI) have been incorporated. Methods This cross-sectional study included 260 non-diabetic adults, 130 with hypothyroidism (case group), and 130 healthy volunteers (control group). Parameters, including Thyroid-Stimulating Hormone (TSH), free thyroxine (T4), fasting blood glucose, HbA1c, insulin levels, and lipid profiles, were measured. IR indices were calculated. Results The groups were matched for age and gender (p = 0.143; p = 0.099). The case group demonstrated a notably elevated mean METS-IR of 195.58, in contrast to the control group's mean METS-IR of 131.10 (p = 0.044). The mean HOMA-IR was significantly higher in the case group than in the control group, with average of 2.00 and 1.81, respectively (p = 0.027). METS-IR was positively correlated with TyG (r = 0.505, p = 0.001) and TG/HDL-C (r = 0.844, p = 0.001). Meanwhile, the relationships between METS-IR, HOMA-IR, and QUICKI were significant at r = 0.194 (p = 0.027) and r = 0.210 (p = 0.016), respectively. METS-IR was significantly higher in patients with overt hypothyroidism (p = 0.016). Conclusion This study emphasizes the efficacy of METS-IR as a diagnostic tool for IR in patients with hypothyroidism, establishing it as a proficient alternative to HOMA-IR. These findings were substantiated by the correlations observed with the TyG, TG/HDL-C, and QUICKI measurements. Variations in METS-IR between individuals with subclinical and overt hypothyroidism accentuate its effectiveness in identifying metabolic abnormalities in hypothyroid conditions.

Objective Post-hoc analysis examined health-related quality of life and esophageal squamous cell carcinoma (ESCC) symptoms in the Asian subgroup of patients in RATIONALE-302 (NCT03430843). Methods: Patients were randomized 1:1 to either tislelizumab or investigator-chosen chemotherapy (paclitaxel, docetaxel, or irinotecan). Health-related quality of life was measured using the EORTC QLQ-C30 and the QLQ-OES18. Least-squares mean score changes from baseline to Weeks 12 and 18 in health-related quality of life scores were assessed using a mixed model for repeated measurements. Reported nominal p-values are for descriptive purpose only. Results: Of the 512 patients, this analysis was conducted in 392 Asian patients (tislelizumab n = 192; investigator-chosen chemotherapy n = 200). The tislelizumab arm had stable GHS/QoL, but fatigue scores worsened in both arms. The change from baseline was similar for physical functioning in both arms at Weeks 12 and 18. Eating and dysphagia scores remained stable in the tislelizumab arm. Reflux improved at Week 12 in the tislelizumab arm and worsened in investigator-chosen chemotherapy arm. Conclusions: Overall, the health-related quality of life and ESCC-related symptoms of patients receiving tislelizumab in the Asian subgroup remained stable or improved, while patients receiving investigator-chosen chemotherapy experienced worsening. These results in Asian patients corroborate the findings in the intent-to-treat population suggesting tislelizumab is a potential new second-line treatment option for patients with advanced or metastatic ESCC. Trial registration: The RATIONALE-302 study is registered on clinicaltrials.gov as NCT03430843.

Objective Zanubrutinib is a highly selective, next-generation Bruton’s tyrosine kinase inhibitor. In the phase 3 SEQUOIA trial (NCT03336333), treatment with zanubrutinib resulted in significantly improved progression-free survival compared to bendamustine plus rituximab (BR) in adult patients with treatment-naïve chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) without del(17p). The current analysis compared the effects of zanubrutinib versus BR on patients’ health-related quality-of-life (HRQoL). Methods In the SEQUOIA trial, patient-reported outcomes (PROs) were assessed at baseline and every 12 weeks (3 cycles) using the EORTC QLQ-C30 and EQ-5D-5L. Descriptive analyses were performed on all the questionnaires’ scales and a mixed model for repeated measures was performed using the key QLQ-C30 endpoints of global health status/QoL (GHS/QoL), physical and role functioning, and symptoms of fatigue, pain, diarrhea, and nausea/vomiting at weeks 12 and 24. Results Compared with BR-treated patients, those in the zanubrutinib arm experienced greater improvements in HRQoL outcomes at both weeks 12 and 24. By week 24, mean change differences (95% confidence interval) between the arms were significant for GHS/QoL (4.9 [0.9, 9.0]), physical functioning (3.8 [0.8, 6.7]), diarrhea (−6.2 [−10.0, −2.5]), fatigue (−4.5 [−8.9, −0.1]), and nausea/vomiting (−4.5 [−8.9, −0.1]); role functioning (4.8 [−0.2, 9.7]) was marginally better in the zanubrutinib arm and there were no differences in pain symptoms (−0.4 [−4.3, 5.1]) between the arms. Conclusions During the first 24 weeks of treatment, zanubrutinib was associated with better HRQoL outcomes in patients with treatment-naive CLL/SLL without del(17p) compared to BR. Trial registration The SEQUOIA trial is registered on clinicaltrials.gov as SEQUOIA trial (NCT03336333).

Objective: Multiple sclerosis is a chronic, demyelinating inflammatory disease of the central nervous system. Medication persistence is defined as an interval between the initiation and last dose of the applied medication and presents a useful surrogate marker of a stable disease course. This observational study aimed to evaluate medication persistence and discontinuation reasons in Slovenian people with multiple sclerosis treated with dimethyl fumarate. Methods: Our retrospective cohort study evaluated people with relapsing-remitting multiple sclerosis treated with dimethyl fumarate as an initial monotherapy or switched from injectable disease-modifying therapy medication between 2014 and 2021. Medication dispenses were extracted from the Slovenian National Institute of Public Health Outpatient Medication Database. The medication persistence criterion was based on the treatment gap. Patients exceeding a 60-day gap were considered nonpersistent. The median time to discontinuation was assessed using survival analyses. Considering discontinuation reasons, patients were further divided into safety and inefficacy groups. Due to the high probability of adverse effects, patients exceeding a 60-day gap were included in the safety group, but definite discontinuation reason remains unknown. The impact of covariates was evaluated by Cox regression. Results: A total of 269 patients were included (183 women, mean age 37 years). During the 7-year follow-up period, 123 (45.7%) patients discontinued treatment. The median time to discontinuation was 5.6 years. After 1, 2, and 5 years of treatment, 84%, 77%, and 57% of patients were found to be persistent, respectively. All patients older than 30 years (p = 0.0013) and among them, those in the inefficacy group (p = 0.037) were more likely to be persistent. Conclusions: The results of our study proved a high persistence rate among our patients. The most frequent discontinuation reason was gastrointestinal adverse effects. Medication persistence requires interventions in younger patients with an unstable disease course.

Objectives We aimed to investigate the risk factors of colistin-associated nephrotoxicity in patients older than 65 years treated in the palliative care unit. Methods 119 palliative care patients who received intravenous colistimethate for at least 7 days were included in the study. The estimated glomerular filtration rate (GFR) was calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation. Data were obtained from the hospital information system. Results The mean age of the participants was 76.7 ± 9.9 years and 49.4% were female. Of the 119 patients, 57 had colistin-induced nephropathy (CIN) according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria. The rate of CIN was higher in women than in men. The baseline phosphate level was higher in the CIN (+) group than in the CIN (–) group. The lower GFR values in patients with pneumonia persisted at days 14 and 30, whereas the lower GFR in patients without pneumonia did not. According to multivariate logistic regression, female gender and baseline phosphate level ≥ 4.5 mg/dl were found as independent variables for the development of nephropathy. Conclusions The creatinine levels of the patients with pneumonia and CIN did not improve after nephrotoxicity, whereas the creatinine levels of the other patients without pneumonia and CIN did. Female gender and baseline phosphate were independent risk factors for CIN. Prolonged kidney failure may lead to a more difficult clinical follow-up process for clinicians. Therefore, clinicians should be aware of persistent renal insufficiency in older patients with pneumonia receiving colistimethate.

Objectives To describe patterns of antiretroviral medications among people with HIV (PWH) who also have common comorbid conditions in a United States cohort. Methods This retrospective cohort study used Optum Research Database claims data from 01/01/2017 through 01/31/2019 to identify adult PWH (≥18 years) based on pharmacy claims for ART during 2018. The index date was defined as the first date of an ART claim. Study inclusion required ≥1 HIV/AIDS diagnosis code during the study period, and continuous health plan enrollment 12 months prior to and at least 30 days after the index date. Descriptive statistics were used to report study results. Results The study population consisted of 17,694 PWH; mean (SD) age 52.2 (12.8) years; 62.0% were ≥ 50 years old. About 50.6% of the study sample had ≥2 comorbidities at baseline. The most prevalent comorbid conditions were hypertension (33.2%), hyperlipidemia (29.7%), neuropsychiatric conditions (26.9%), and cardiovascular disease (11.5%). Most (93.5%) of PWH received a nucleotide reverse transcriptase inhibitor (NRTI) backbone regimen, including tenofovir alafenamide (41.6%), tenofovir disoproxil fumarate (28.1%), and abacavir (22.0%). The most commonly used anchor agents, 62.6%, were integrase strand transfer inhibitors (INSTIs): dolutegravir (30.4%), elvitegravir (24.2%), and raltegravir (7.3%). The proportion of PWH using specific ARTs did not vary significantly with the presence and type of comorbidities. Conclusion From our analyses, ART prescribing did not appear to vary with the presence of comorbidities and potential medication contraindications. ART regimens may have comparable efficacy profiles; however, selection should be guided by each patient’s comorbidities to prevent potential comedication drug toxicities.

The increasing use of RWE in regulatory and reimbursement decision-making indicates the significant progress that has been made in building trust in RWE through greater transparency. This review of the published literature and key online sources was conducted to provide an update on progress towards greater transparency in RWE, based on four key barriers to trust identified in a 2016 paper and applying learnings from transparency initiatives established for RCTs, such as the US FDA Amendments Act (FDAAA) 2007 Final Rule. Multiple initiatives from the US FDA, EMA and organizations such as the ISPOR-ISPE Joint Task Force have yielded new guidance documents and tools that enable greater transparency in RWE study methodology (STaRT-RWE and HARPER templates), data source selection and quality (SPIFD2 framework, REQueST tool), strategy (the Center for Open Science RWE Study Registry), and will therefore improve transparency in RWE study reporting. Programs such as the REPEAT Initiative and RWE DUPLICATE are investigating reproducibility of RWE studies and improving understanding of the circumstances when valid inference on treatment effects can be obtained from RWE studies. Further work is needed to embed and to implement the new tools and guidance that are available, and thus raise standards for RWE transparency towards the levels expected for RCTs.