Search

Background: New daily persistent headache (NDPH) is a continuous, unremitting headache from onset that yields suboptimal results with traditional medicines. Repetitive transcranial magnetic stimulation (rTMS) has emerged as a promising non-invasive treatment for other headache disorders, such as migraine, and neuromodulation has not been well-studied in NDPH. The objective of the study was to evaluate the efficacy of rTMS in reducing the frequency and severity of headaches, and associated anxiety and depressive symptoms in NDPH patients. Methods: This was an open label prospective, single arm, interventional pilot study conducted between October 2022 and September 2023. All eligible participants received 10 Hz rTMS (600 pulses, 10 trains), delivered to the left prefrontal cortex for three consecutive days. The post-rTMS headache severity was recorded weekly for four weeks and headache free days/functional disability, PHQ-9, and GAD-7 scores at the end of four weeks and compared with pre-rTMS parameters. The primary outcome was defined by ≥ 50% reduction in headache severity on Visual Analogue Scale (VAS) score, decrease in headache days from the baseline and secondary outcome was ≥ 6 point reduction in HIT-6 score at 4 weeks. Results: Fifty NDPH patients (mean [SD] age, 35.06 [13.91] years; 31 females [62%]) participated in this study. Thirty-five patients (70%) reported ≥ 50% improvement in pain severity (p-value < 0.001), with a mean reduction of 10.84 (4.88) headache days per 28 days from a baseline of 28 headache days (p-value < 0.001). Thirty-eight patients (76%) reported a ≥ 6 point's reduction in HIT score at 4 weeks. Maximum improvement in the above parameters was observed in NDPH patients with chronic migraine. Two patients reported intolerance to the sound of the rTMS. The median (IQR) PHQ-9 and GAD-7 scores reduced from 11.5(3.75,20) to 7(2,15) (p-value < 0.001) and 10(3,14) to 5.5(0,9) (p-value < 0.001) respectively. Conclusion: rTMS was well tolerated and effective in reducing pain severity, headache days and headache related disability, depressive and anxiety symptoms. Trial registration: CTRI/2023/05/053247. [ABSTRACT FROM AUTHOR]

Background: Improvements in oxygenation and lung mechanics with prone position (PP) in patients with acute respiratory distress syndrome (ARDS) are inconstant. The objectives of the study were (i) to identify baseline variables, including the recruitment-to-inflation ratio (R/I), associated with a positive response to PP in terms of oxygenation (improvement of the ratio of arterial oxygen partial pressure over the inspired oxygen fraction (PaO2/FiO2) ≥ 20 mmHg) and lung mechanics; (ii) to evaluate whether the response to the previous PP session is associated with the response to the next session. Methods: In this prospective, observational, single-center study in patients who underwent PP for ARDS due to COVID-19, respiratory variables were assessed just before PP and at the end of the session. Respiratory variables included mechanical ventilation settings and respiratory mechanics variables, including R/I, an estimate of the potential for lung recruitment compared to lung overinflation. Results: In 50 patients, 201 PP sessions lasting 19 ± 3 h were evaluated. Neuromuscular blockades were used in 116 (58%) sessions. The PaO2/FiO2 ratio increased from 109 ± 31 mmHg to 165 ± 65 mmHg, with an increase ≥ 20 mmHg in 142 (71%) sessions. In a mixed effect logistic regression, only pre-PP PaO2/FiO2 (OR 1.12 (95% CI [1.01–1.24])/every decrease of 10 mmHg, p = 0.034) in a first model and improvement in oxygenation at the previous PP session (OR 3.69 (95% CI [1.27–10.72]), p = 0.017) in a second model were associated with an improvement in oxygenation with PP. The R/I ratio (n = 156 sessions) was 0.53 (0.30–0.76), separating lower- and higher-recruiters. Whereas PaO2/FiO2 improved to the same level in both subgroups, driving pressure and respiratory system compliance improved only in higher-recruiters (from 14 ± 4 to 12 ± 4 cmH2O, p = 0.027, and from 34 ± 11 to 38 ± 13 mL/cmH2O, respectively, p = 0.014). Conclusions: A lower PaO2/FiO2 at baseline and a positive O2-response at the previous PP session are associated with a PP-induced improvement in oxygenation. In higher-recruiters, lung mechanics improved along with oxygenation. Benefits of PP could thus be greater in these patients. [ABSTRACT FROM AUTHOR]

Background: The posterior ethmoid sinuses have a complex anatomy and a highly variable normal structure. The posterior ethmoid Onodi cell needs careful assessment because of its proximity to the optic nerve and the internal carotid artery canal. Recognising the distinctions is essential for optimal pre-op preparation. Sphenoid sinus surgery can now be performed without worrying about compromising vital structures like the internal carotid artery or optic nerve. Preoperative radiological assessment is a quick and easy way to check for ethmoid cell pneumatisation differences. Aim and objectives: To determine the pneumatisation patterns of Onodi cells among the North-East Indian population using 16-slice multidetector computed tomography (MDCT). Results: Nine-hundred MDCT paranasal sinuses were analysed over a period of 0–2 years, out of which 220 cases showed the presence of Onodi cell. Type I were 89 cases (40.45%, CI 32.00–48.90), Type II were 128 cases (58.18%, CI 49.72–66.63), and 3 cases with Type III cell (1.36%, CI 0.18–2.54). Conclusion: The most prevalent pneumatisation pattern is Type II. The pneumatisation patterns of Onodi cells can be best detected and evaluated by multiplanar MDCT imaging. Sinus surgeons need a firm grasp of pneumatisation patterns to avoid damaging the optic nerve and internal carotid artery canal during operations. [ABSTRACT FROM AUTHOR]

Background: The difficulty in understanding speech becomes worse in the presence of background noise for individuals with sensorineural hearing loss. Speech-in-noise tests help to assess this difficulty. Previously, the Tulu sentence lists have been assessed for their equivalency to measure speech recognition threshold in noise among individuals with normal hearing. The present study aimed to determine the equivalence and test–retest reliability of Tulu sentence lists for measuring speech recognition threshold in noise among individuals with sensorineural hearing loss. Results: The SNR-50 was measured for 13 sentence lists in 20 Tulu-speaking individuals with mild to moderate sensorineural hearing loss. Retesting was done by administering all lists to eight participants after an average of 25.25 days (SD = 19.44). Friedman test was administered to check for the list equivalency. Intraclass correlation coefficient was measured to assess test–retest reliability. A regression analysis was performed to understand the influence of pure-tone average on SNR-50. A Kruskal–Wallis test was administered to check the statistical significance of the SNR-50 obtained across different configurations and degrees of hearing loss. Nine of the 13 Tulu sentence lists (lists 2, 4, 5, 6, 9, 10, 11, 12, and 13) were equivalent in individuals with sensorineural hearing loss. The mean SNR-50 for these nine lists was 1.13 dB (SD = 2.04 dB). The test–retest reliability was moderate (ICC = 0.727). The regression analysis showed that a pure-tone average accounted for 24.7% of the variance in SNR-50 data (p = 0.026). Individuals with mild to moderate hearing loss obtained the worst SNR-50, followed by mild and high-frequency hearing loss. Conclusion: Nine Tulu sentence lists are equivalent and reliable and can be used to measure speech recognition threshold in noise among individuals with sensorineural hearing loss who are Tulu speakers. [ABSTRACT FROM AUTHOR]

E-mental health (EMH) interventions gain increasing importance in the treatment of mental health disorders. Their outpatient efficacy is well-established. However, research on EMH in inpatient settings remains sparse and lacks a meta-analytic synthesis. This paper presents a meta-analysis on the efficacy of EMH in inpatient settings. Searching multiple databases (PubMed, ScienceGov, PsycInfo, CENTRAL, references), 26 randomized controlled trial (RCT) EMH inpatient studies (n = 6112) with low or medium assessed risk of bias were included. A small significant total effect of EMH treatment was found (g = 0.3). The effect was significant both for blended interventions (g = 0.42) and post-treatment EMH-based aftercare (g = 0.29). EMH treatment yielded significant effects across different patient groups and types of therapy, and the effects remained stable post-treatment. The results show the efficacy of EMH treatment in inpatient settings. The meta-analysis is limited by the small number of included studies. [ABSTRACT FROM AUTHOR]

We aimed to identify and characterise behavioural profiles in patients at high risk of SCD, by using deep representation learning of day-to-day behavioural recordings. We present a pipeline that employed unsupervised clustering on low-dimensional representations of behavioural time-series data learned by a convolutional residual variational neural network (ResNet-VAE). Data from the prospective, observational SafeHeart study conducted at two large tertiary university centers in the Netherlands and Denmark were used. Patients received an implantable cardioverter-defibrillator (ICD) between May 2021 and September 2022 and wore wearable devices using accelerometer technology during 180 consecutive days. A total of 272 patients (mean age of 63.1 ± 10.2 years, 81% male) were eligible with a total sampling of 37,478 days of behavioural data (138 ± 47 days per patient). Deep representation learning identified five distinct behavioural profiles: Cluster A (n = 46) had very low physical activity levels and a disturbed sleep pattern. Cluster B (n = 70) had high activity levels, mainly at light-to-moderate intensity. Cluster C (n = 63) exhibited a high-intensity activity profile. Cluster D (n = 51) showed above-average sleep efficiency. Cluster E (n = 42) had frequent waking episodes and poor sleep. Annual risks of malignant ventricular arrhythmias ranged from 30.4% in Cluster A to 9.8% and 9.5% for Clusters D-E, respectively. Compared to low-risk profiles (D-E), Cluster A demonstrated a three-to-four fold increased risk of malignant ventricular arrhythmias adjusted for clinical covariates (adjusted HR 3.63, 95% CI 1.54–8.53, p < 0.001). These behavioural profiles may guide more personalised approaches to ventricular arrhythmia and SCD prevention. [ABSTRACT FROM AUTHOR]

Background: Cardiac arrest remains a global health issue with limited data on long-term outcomes, particularly regarding recurrent cardiovascular events in patients surviving out-of-hospital cardiac arrest. (OHCA). We aimed to describe the long-term occurrence of major cardiac event defined by hospital admission for cardiovascular events or death in OHCA hospital survivors, whichever came first. Our secondary objective were to assess separately occurrence of hospital admission and death, and to identify the factors associated with major event occurrence. We hypothesized that patients surviving an OHCA has a protracted increased risk of cardiovascular events, due to both presence of the baseline conditions that lead to OHCA, and to the cardiovascular consequences of OHCA induced acute ischemia-reperfusion. Methods: Consecutive OHCA patients from three hospitals of Sudden Death Expertise Center (SDEC) Registry, discharged alive from 2011 to 2015 were included. Long-term follow-up data were obtained using national inter-regime health insurance information system (SNIIRAM) database and the national French death registry. The primary endpoint was occurrence of a major event defined by hospital admission for cardiovascular events and death, whichever came first during the follow-up. The starting point of the time-to-event analysis was the date of hospital discharge. The follow-up was censored on the date of the first event. For patients without event, follow-up was censored on the date of December, 29th, 2016. Results: A total of 306 patients (mean age 57; 77% male) were analyzed and followed over a median follow-up of 3 years for hospital admission for cardiovascular event and 6 years for survival. During this period, 38% patients presented a major event. Hospital admission for cardiovascular events mostly occurred during the first year after the OHCA whereas death occurred more linearly during the all period. A previous history of chronic heart failure and coronary artery disease were independently associated with the occurrence of major event (HR 1.75, 95%CI[1.06-2.88] and HR 1.70, 95%CI[1.11-2.61], respectively), whereas post-resuscitation myocardial dysfunction, cardiogenic shock and cardiologic cause of cardiac arrest did not. Conclusion: Survivors from OHCA must to be considered at high risk of cardiovascular event occurrence whatever the etiology, mainly during the first year following the cardiac arrest and should require closed monitoring. [ABSTRACT FROM AUTHOR]

This study aimed to investigate whether metabolic dysfunction-associated fatty liver disease (MAFLD) defined by the fatty liver index (FLI) affects the decline in kidney function and whether this relationship is still observed in MAFLD defined by ultrasonography (USG). A retrospective cohort study was conducted using de-identified data from participants who received health checkups at Samsung Changwon Hospital between 2002 and 2018. The primary and secondary exposures were the presence of FLI- and USG-defined MAFLD, respectively. The primary outcome was 5-years slope of eGFR. The secondary outcome was a rapid decline in kidney function, defined as a 5-years slope of estimated glomerular filtration rate (eGFR) of less than − 3 mL/min/1.73 m2 per year. A total of 37,500 participants were included in the analysis. Participants with FLI-defined MAFLD had a larger decline in 5-year eGFR slope than those without FLI-defined MAFLD (beta coefficients − 0.11; 95% CI − 0.14 to − 0.08). Participants with FLI-defined MAFLD had a higher risk of rapid kidney function decline than those without FLI-defined MAFLD (odds ratio 1.33; 95% confidence intervals (CIs) 1.05–1.69). However, USG-defined MAFLD was less related to kidney function decline. In conclusion, the presence of FLI-defined MAFLD was associated with larger and faster kidney function decline. [ABSTRACT FROM AUTHOR]

Background: Acute respiratory distress syndrome (ARDS) occurring in patients with hematological malignancies (HM) is a life-threatening condition with specific features. Mortality rate remains high but improvement has been described over the past several years. We aimed to describe characteristics and outcomes of ARDS in HM patients admitted in French ICUs (Intensive Care Units) during a one year-period. Data for this nationwide cohort study were collected from the French national hospital database (Programme de Médicalisation des Systèmes d'Information (PMSI)). All patients (18 years or older) admitted to French ICUs in 2017 and with a diagnosis of ARDS were included. Three groups were compared according to the presence of an HM, a solid cancer or no cancer. The primary endpoint was 90-day mortality. Secondary endpoints were the description of ICU management, etiologies of ARDS and mortality risk factors. Results: A total of 12 846 patients with ARDS were included. Among them, 990 had HM and 2744 had a solid cancer. The main malignancies were non-Hodgkin lymphoma (NHL) (28.5%), acute myeloid leukemia (AML) (20.4%) and multiple myeloma (19.7%). Day-90 mortality in patients with HM was higher than in patients with no cancer (64.4% vs. 46.6% p = 0.01) but was not different from that of patients with solid cancer (64.4% vs. 61.4%,p = 0.09). Intubation rate was lower in patients with HM in comparison with both groups (87.7% vs. 90.4% p = 0.02 for patients with solid cancer and 87.7% vs. 91.3%; p < 0.01 with no cancer). Independent predictors of mortality for patients with HM were a diagnosis of lymphoma or acute leukemia, age, a high modified SAPS II score, a renal replacement therapy, invasive fungal infection, and a septic shock. Bacterial pneumonia, extrapulmonary infections and non-invasive ventilation were protective. Conclusion: Mortality remains high in patients with HM admitted in ICU with ARDS in comparison with patients without cancer. Mortality predictors for this population were a diagnosis of lymphoma or acute leukemia, age, a high modified SAPS II score, a renal replacement therapy, invasive fungal infection and a septic shock. [ABSTRACT FROM AUTHOR]

Background: Maintaining the dose-intensity of cancer treatment is an important prognostic factor of aggressive hematological malignancies. The objective of this study was to assess the long-term outcomes of intensive care unit (ICU) survivors with acute myeloid leukemia (AML) or aggressive B-cell non-Hodgkin lymphoma (B-NHL) with emphasis on the resumption of the intended optimal regimen of cancer treatment. Patients and methods: We conducted a retrospective (2013–2021) single-center observational study where we included patients with AML and B-NHL discharged alive from the ICU after an unplanned admission. The primary endpoint was the change in the intended optimal cancer treatment following ICU discharge. Secondary endpoints were 1-year progression-free survival and overall survival rates. Determinants associated with modifications in cancer treatment were assessed through multivariate logistic regression. Results: Over the study period, 366 patients with AML or B-NHL were admitted to the ICU, of whom 170 survivors with AML (n = 92) and B-NHL (n = 78) formed the cohort of interest. The hematological malignancy was recently diagnosed in 68% of patients. The admission Sequential Organ Failure Assessment (SOFA) score was 5 (interquartile range 4–8). During the ICU stay, 30 patients (17.6%) required invasive mechanical ventilation, 29 (17.0%) vasopressor support, and 16 (9.4%) renal replacement therapy. The one-year survival rate following ICU discharge was 59.5%. Further modifications in hematologic treatment regimens were required in 72 patients (42%). In multivariate analysis, age > 65 years (odds ratio (OR) 3.54 [95%-confidence interval 1.67–7.50], p < 0.001), ICU-discharge hyperbilirubinemia > 20 µmol/L (OR 3.01 [1.10–8.15], p = 0.031), and therapeutic limitations (OR 16.5 [1.83–149.7], p = 0.012) were independently associated with modifications in cancer treatment. Post-ICU modifications of cancer treatment had significant impact on in-hospital, 1-year overall survival and progression-free survival. Conclusion: The intended cancer treatment could be resumed in 58% of ICU survivors with aggressive hematological malignancies. At the time of ICU discharge, advanced age, persistent liver dysfunction and decisions to limit further life-support therapies were independent determinants of cancer treatment modifications. These modifications were associated with worsened one-year outcomes. [ABSTRACT FROM AUTHOR]

This paper reports the results of a hybrid effectiveness-implementation randomized trial that systematically varied levels of human oversight required to support the implementation of a digital medicine intervention for persons with mild-to-moderate alcohol use disorder (AUD). Participants were randomly assigned to three groups representing possible digital health support models within a health system: self-monitored use (SM; n = 185), peer-supported use (PS; n = 186), or a clinically integrated model CI; (n = 187). Across all three groups, the percentage of self-reported heavy drinking days dropped from 38.4% at baseline (95% CI [35.8%, 41%]) to 22.5% (19.5%, 25.5%) at 12 months. The clinically integrated group showed significant improvements in mental health and quality of life compared to the self-monitoring group (p = 0.011). However, higher attrition rates in the clinically integrated group warrant consideration in interpreting this result. Results suggest that making a self-guided digital intervention available to patients may be a viable option for health systems looking to promote alcohol risk reduction. This study was prospectively registered at clinicaltrials.gov on 7/03/2019 (NCT04011644). [ABSTRACT FROM AUTHOR]

To better understand the impact of Long COVID on an individual, we explored changes in daily wearable data (step count, resting heart rate (RHR), and sleep quantity) for up to one year in individuals relative to their pre-infection baseline among 279 people with and 274 without long COVID. Participants with Long COVID, defined as symptoms lasting for 30 days or longer, following a SARS-CoV-2 infection had significantly different RHR and activity trajectories than those who did not report Long COVID and were also more likely to be women, younger, unvaccinated, and report more acute-phase (first 2 weeks) symptoms than those without Long COVID. Demographic, vaccine, and acute-phase sensor data differences could be used for early identification of individuals most likely to develop Long COVID complications and track objective evidence of the therapeutic efficacy of any interventions. Trial Registration: https://classic.clinicaltrials.gov/ct2/show/NCT04336020. [ABSTRACT FROM AUTHOR]

Background: As a novel and time-efficient exercise form, high-intensity interval training (HIIT) has shown great potential in improving health-related physical fitness among diverse populations. However, empirical evidence on its efficacy among the elderly has not been well summarized. This systematic review and meta-analysis aimed to determine the effect of HIIT interventions on the parameters related to physical fitness and health of older adults, including resting heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), cardiorespiratory fitness (CRF), body mass index (BMI), body fat percent (BF%), waist circumference (WC), muscular endurance (ME), muscular strength (MS), muscular power (MP), balance and flexibility, compared to non-exercise and other-exercise (e.g., moderate-intensity continuous training, resistance training) conditions. Methods: Literature published from January 2000 to May 2023 was collected through extensive searches across eight databases and relevant review papers. Randomized controlled trials (RCTs) featuring a minimum 2-week exercise intervention for older adults (≥ 60 years) were included. The pooled effect size of Hedges'g was estimated using random-effects models in R. Meta-regression was performed for both categorical (health status, duration of training programme, and frequency) and continuous moderators (mean age, male rate, and attrition rate). Results: Forty-four eligible RCTs with 1863 participants (52.1% female; 60.5–81.2 years) were included in the quantitative analysis. Compared to non-exercise condition, HIIT significantly improved resting HR (g = -0.36, 95%CI = [-0.67, -0.05], P = 0.032), SBP (g = -0.29, 95%CI = [-0.54, -0.03], P = 0.008), CRF (g = 0.77, 95%CI = [0.51, 1.04], P < 0.001), BF% (g = -0.26, 95%CI = [-0.41, -0.11], P = 0.006), MS (g = 0.47, 95%CI = [0.23, 0.71], P = 0.004), ME (g = 0.65, 95%CI = [0.10, 1.19], P = 0.036), and balance (e.g., timed-up-and-go) (g = -0.79, 95%CI = [-1.19, -0.40], P = 0.035). Compared to other-exercise condition, HIIT significantly improved resting HR (g = -0.11, 95%CI = [-0.21, -0.01], P = 0.029), SBP (g = -0.14, 95%CI = [-0.28, -0.01], P = 0.038), and CRF (g = 0.23, 95%CI = [0.07, 0.38], P = 0.008). No significant difference was found between HIIT and non-exercise condition for DBP, BMI and WC, as well as between HIIT and other-exercise condition for DBP, BMI, BF%, WC, ME, and balance (all P > 0.05). Meta-regression indicated that mean age moderated the HIIT effect on resting HR (b = -0.02, P = 0.014; HIIT vs. other-exercise condition) and SBP (b = 0.03, P = 0.048; HIIT vs. non-exercise), and attrition rate moderated the effect on CRF (b = 0.03, P = 0.007; HIIT vs. non-exercise). Conclusion: This study supports the efficacy of HIIT in improving resting HR, SBP, CRF, BF%, MS, ME and balance among older adults. More empirical evidence is needed to determine the efficacy of HIIT for MP and flexibility in this population. Trial Registration: PROSPERO CRD42022316246. Key Points: • HIIT is an effective approach for improving older adults' resting heart rate (HR), systolic blood pressure (SBP), cardiorespiratory fitness (CRF), body fat percent (BF%), muscular strength (MS), and balance, compared with non-exercise condition. • HIIT outperformed the other exercise interventions in improving older adults' resting HR, SBP, CRF, and muscular endurance (ME). • Mean age and attrition rate were identified as potential moderators for the HIIT effects on resting HR, SBP and CRF. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global health threat. This randomized controlled trial evaluates the impact of experiential virtual reality (VR) versus information provision via VR or leaflet on prudent antibiotic use. A total of 249 (239 analyzed) participants were randomized into three conditions: VR Information + Experience, VR Information, or Leaflet Information. All participants received AMR information, while those in the VR Information + Experience condition additionally engaged in a game, making treatment decisions for their virtual avatar's infection. Participants in the VR Information + Experience condition showed a significant increase in prudent use intentions from baseline (d = 1.48). This increase was significantly larger compared to the VR Information (d = 0.50) and Leaflet Information (d = 0.79) conditions. The increase in intentions from baseline remained significant at follow-up in the VR Information + Experience condition (d = 1.25). Experiential VR communication shows promise for promoting prudent antibiotics use. [ABSTRACT FROM AUTHOR]

Introduction and background: The musculoskeletal pain (MSK) develops at an early age and pains in adolescence dispose to subsequent pain episodes in adulthood. High physical fitness levels in childhood and adolescence are linked to favorable health outcomes. This study has evaluated the prevalence of musculoskeletal pain among school students. Additionally, it examines the existing physical fitness of those children and explores potential associations between musculoskeletal pain and physical fitness. Methods: A cross sectional study was conducted in the Guwahati urban area, a capital city of North East India, in different schools. The mean and standard deviation of age was 9.49 ± 2.53. Prevalence of MSK pain was determined by the Faces Pain Scale–Revised and pediatric Gait Arm Leg Spine (pGALS) assessment, whereas physical fitness was assessed by Fitnessgram test battery. Statistical analysis: Paired "t" test and logistic regression analysis were used. The level of significance was set at 0.05 for all tests performed, and 95% confidence intervals (CIs) were used in all cases. Results: The percentage of musculoskeletal pain is 38.28% where female school students have 40.33% and the male students have 36.52%. The odd ratio of 0.934 (CI = 0.916–0.972) was found between pain occurrence and aerobic capacity. The odd ratio of 0.72 (CI = 0.704–0.761) was found between the chances of pain onset and abdominal strength and endurance. The odd ratio of 0.859 (CI = 0.831–0.899) was found between pain occurrence and trunk extensor muscle strength and endurance. Conclusion: The prevalence of the musculoskeletal pain in school students is found to be 38.28%. The incidence of musculoskeletal pain and the physical fitness of a child has a significant relationship, with children who have poor physical fitness being more likely to develop musculoskeletal pain. [ABSTRACT FROM AUTHOR]

In pandemic mitigation, strategies such as social distancing and mask-wearing are vital to prevent disease resurgence. Yet, monitoring adherence is challenging, as individuals might be reluctant to share behavioral data with public health authorities. To address this challenge and demonstrate a framework for conducting observational research with sensitive data in a privacy-conscious manner, we employ a privacy-centric epidemiological study design: the federated cohort. This approach leverages recent computational advances to allow for distributed participants to contribute to a prospective, observational research study while maintaining full control of their data. We apply this strategy here to explore pandemic intervention adherence patterns. Participants (n = 3808) were enrolled in our federated cohort via the "Google Health Studies" mobile application. Participants completed weekly surveys and contributed empirically measured mobility data from their Android devices between November 2020 to August 2021. Using federated analytics, differential privacy, and secure aggregation, we analyzed data in five 6-week periods, encompassing the pre- and post-vaccination phases. Our results showed that participants largely utilized non-pharmaceutical intervention strategies until they were fully vaccinated against COVID-19, except for individuals without plans to become vaccinated. Furthermore, this project offers a blueprint for conducting a federated cohort study and engaging in privacy-preserving research during a public health emergency. [ABSTRACT FROM AUTHOR]

Physical activity or structured exercise is beneficial in a wide range of circumstances. Nevertheless, individual-level data on differential responses to various types of activity are not yet sufficient in scale, duration or level of annotation to understand the mechanisms of discrete outcomes nor to support personalized recommendations. The Apple Heart & Movement Study was designed to passively collect the dense physiologic data accessible on Apple Watch and iPhone from a large real-world cohort distributed across the US in order to address these knowledge gaps. [ABSTRACT FROM AUTHOR]

Background: The University of Jyvaskyla Active Aging Scale (UJACAS) assesses active aging through willingness, ability, opportunity, and frequency of involvement in activities. Recognizing the lack of a German version, the Finnish original was translated (UJACAS-G). This study aimed: (1) to evaluate the test-retest reliability of UJACAS-G; and (2) to explore correlations with health-related parameters (concurrent validity). Methods: The study (test-retest design) targeted healthy older adults aged 65+. Reliability of UJACAS-G (total and subscores) was assessed using Bland-Altman analyses and Intraclass Correlation Coefficients (ICCs). Furthermore, correlations (Spearman's rho) between UJACAS-G scores and physical function (walking speed, handgrip strength, balance, 6-minute walk distance), physical activity (International Physical Activity Questionnaire), life-space mobility (Life-Space Assessment), and health-related quality of life (Short Form-36 Health Survey) were calculated. Results: Bland-Altman analyses (N = 60; mean age 72.3, SD 5.9 years; 50% women) revealed mean differences close to zero and narrow limits of agreement for all scores (total score: mean difference −1.9; limits −31.7 to 27.9). The ability subscore showed clustering at its upper limit. ICC was 0.829 (95% CI 0.730 to 0.894) for the total score and ranged between 0.530 and 0.876 for subscores (all p-values < 0.001). The total score correlated with walking speed (rho = 0.345; p = 0.008), physical activity (rho = 0.279; p = 0.033) and mental health (rho = 0.329; p = 0.010). Conclusions: UJACAS-G is reliable for assessing active aging among German-speaking healthy older adults. A potential 'ceiling effect' regarding the ability subscore should be considered when applying UJACAS-G to well-functioning populations. Analyses of concurrent validity indicated only weak correlations with health-related parameters. [ABSTRACT FROM AUTHOR]

Background: In recent years, there has been a growing number of thefts of firearms stored in vehicles. Despite this trend, there is limited research on firearm storage patterns in vehicles in the United States. This study investigates these storage patterns and evaluates the relationship between the surge in firearm purchases after March 2020 and the practice of storing firearms in vehicles. Methods: Firearm storage practices were classified into four categories: (a) no vehicle storage, (b) locked vehicle storage only, (c) unlocked vehicle storage only, and (d) both locked and unlocked vehicle storage. Multinomial logistic regression analyses were conducted to determine the association between vehicle firearm storage practices and the main independent variable (firearm purchases since March 2020), adjusting for covariates. Results: Those who purchased a firearm since March 2020 were significantly more likely to store at least one firearm in a vehicle unlocked only (RRR = 2.41, 95% CI 1.45–3.99) or both locked and unlocked (RRR = 2.57, 95% CI.180–3.67) compared to the reference category of no vehicle storage. Conclusion: Individuals who purchased a firearm after March 2020 were more likely to report storing a firearm in a vehicle. Given the limited research on patterns of firearm storage in vehicles, these findings provide novel evidence suggesting that firearm purchases following the March 2020 firearm purchasing surge may have fomented behaviors that increased the likelihood of firearm storage in automobiles. Moving forward, there is a need for additional quantitative and qualitative research that can better understand patterns and motivations of firearm storage in vehicles. [ABSTRACT FROM AUTHOR]

Partial accelerated life tests (PALTs) are employed when the results of accelerated life testing cannot be extended to usage circumstances. This work discusses the challenge of different estimating strategies in constant PALT with complete data. The lifetime distribution of the test item is assumed to follow the power half-logistic distribution. Several classical and Bayesian estimation techniques are presented to estimate the distribution parameters and the acceleration factor of the power half-logistic distribution. These techniques include Anderson–Darling, maximum likelihood, Cramér von-Mises, ordinary least squares, weighted least squares, maximum product of spacing and Bayesian. Additionally, the Bayesian credible intervals and approximate confidence intervals are constructed. A simulation study is provided to compare the outcomes of various estimation methods that have been provided based on mean squared error, absolute average bias, length of intervals, and coverage probabilities. This study shows that the maximum product of spacing estimation is the most effective strategy among the options in most circumstances when adopting the minimum values for MSE and average bias. In the majority of situations, Bayesian method outperforms other methods when taking into account both MSE and average bias values. When comparing approximation confidence intervals to Bayesian credible intervals, the latter have a higher coverage probability and smaller average length. Two authentic data sets are examined for illustrative purposes. Examining the two real data sets shows that the value methods are workable and applicable to certain engineering-related problems. [ABSTRACT FROM AUTHOR]

Background: Idiopathic intracranial hypertension (IIH) is a neurological disorder characterized by increased intracranial pressure. Whilst lumbar puncture (LP) is necessary for the diagnosis of IIH, its therapeutic effect remains unclear. Our aim was to evaluate the therapeutic effect of a single LP in people with IIH (pwIIH). Methods: In this prospective observational study, we analysed short-term neurological and ophthalmological outcomes in pwIIH before, one (D1) and seven days (D7) after the LP. The primary outcome was the change in papilledema degree from baseline. Secondary outcomes included visual outcomes, morphological changes in optical coherence tomography (peripapillary retinal nerve fibre layer [pRNFL] thickness and ganglion cell layer [GCL] volume) and transbulbar sonography (arachnoid optic nerve sheath diameter [AONSD]), and headache outcomes (peak and median headache severity and burden related to headache). Results: We included 30 pwIIH (mean age 32.8 years [SD 8.4], 93.3% female, median cerebrospinal fluid [CSF] opening pressure 33.0 cmCSF [IQR 26.9–35.3], median body mass index (BMI) 34.8 kg/m2 [IQR 30.9–40.9]). The median papilledema grading at baseline was 2 (Friedman DI (1999) Pseudotumor cerebri. Neurosurg Clin N Am 10(4):609–621 viii); (Mollan SP, Aguiar M, Evison F, Frew E, Sinclair AJ (2019) The expanding burden of idiopathic intracranial hypertension. Eye Lond Engl 33(3):478–485); (Ab D, Gt L, Nj V, Sl G, Ml M, Nj N et al. (2007) Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol [Internet]. Apr [cited 2024 Jun 2];143(4). https://pubmed.ncbi.nlm.nih.gov/17386271/) and was significantly reduced at D7 (2 [1–2], p = 0.011). Median pRNFL thickness had decreased significantly at D7 (-9 μm [-62.5, -1.3], p = 0.035), with pRNFL thickness at baseline being associated with the pRNFL change (F(1,11) = 18.79, p = 0.001). Mean AONSD had decreased significantly at both D1 (-0.74 mm [0.14], p < 0.001) and D7 (-0.65 mm [0.17], p = 0.01), with AONSD at baseline being associated with the change in AONSD at both time points (D1: β= -0.89, 95% CI -1.37, -0.42, p = 0.002; D7: β= -0.85, 95% CI -1.42, -0.28, p = 0.007). Peak headache severity was slightly lower at D7 (-1/10 [-3, 0], p = 0.026), whereas median headache severity and headache burden remained unchanged. Conclusions: This short-term follow-up study in pwIIH undergoing a single LP suggests a moderate effect on ophthalmological but not headache outcomes. The usefulness of LP as a therapeutic measure in IIH remains controversial and should likely be reserved for patients with limited treatment options, e.g., in pregnancy or intolerability to medication. [ABSTRACT FROM AUTHOR]

Large language models (LLMs) hold great promise in summarizing medical evidence. Most recent studies focus on the application of proprietary LLMs. Using proprietary LLMs introduces multiple risk factors, including a lack of transparency and vendor dependency. While open-source LLMs allow better transparency and customization, their performance falls short compared to the proprietary ones. In this study, we investigated to what extent fine-tuning open-source LLMs can further improve their performance. Utilizing a benchmark dataset, MedReview, consisting of 8161 pairs of systematic reviews and summaries, we fine-tuned three broadly-used, open-sourced LLMs, namely PRIMERA, LongT5, and Llama-2. Overall, the performance of open-source models was all improved after fine-tuning. The performance of fine-tuned LongT5 is close to GPT-3.5 with zero-shot settings. Furthermore, smaller fine-tuned models sometimes even demonstrated superior performance compared to larger zero-shot models. The above trends of improvement were manifested in both a human evaluation and a larger-scale GPT4-simulated evaluation. [ABSTRACT FROM AUTHOR]

Background: U.S. firearm sales surged during the COVID-19 pandemic, with many purchases by first-time firearm owners. The 2023 National Survey of Gun Policy sought to understand the public health implications of this surge by comparing the purchasing motivations and firearm policy views of pandemic-era first-time purchasers to prior gun owners. Methods: We fielded a nationally representative public opinion survey of U.S. adults (n = 3096) from 1/4/23 to 2/6/23. We oversampled for gun owners and Black, Hispanic, and Asian Americans. Survey weights were applied to generate representative estimates. New gun owners were identified through affirmative responses to: "Have you bought any guns since January 1, 2020?" and "Did you buy your first gun after January 1, 2020?" Recent purchasers were additionally asked whether concerns of 1) political or 2) racial violence motivated their purchase. Purchase motivations and gun policy support were examined among new and prior gun owners (n = 1002) and compared using logistic regression and predictive probabilities. Results: Overall, 11% of respondents reported purchasing a gun since 1/1/20, 35% for the first time. Among recent purchasers, larger proportions of Democrat, Black, Asian, and Hispanic respondents were new gun owners than Republican or white respondents. Compared to prior owners, odds were 4.5-times higher that new gun owners' recent purchase was motivated by racial violence and 3.2-times higher for political violence. Majority support was found for protective gun policies, with few differences by purchase recency or motivations. The only policy for which support by new and prior gun owners differed significantly was the permit-to-purchase policy (76% v. 63%, respectively). Similarly, few significant differences in support were observed when stratifying by purchase motivation. Notably, both those who reported recent purchase motivations of racial violence and of political violence expressed significantly higher support for a "stand-your-ground" policy compared to those who did not report such motivations. Conclusions: Racial and political violence appear to be larger concerns among new gun owners, motivating purchasing among demographic groups with traditionally lower gun ownership rates. These findings suggest a need for safety assurances amid racial and political tensions and growing gun ownership. Gun owners' support for such policies remains strong. [ABSTRACT FROM AUTHOR]

Background: Bleeding in early pregnancy is a common emergency department (ED) presentation. Although variability in approaches has been demonstrated, research is relatively uncommon on practices and outcomes. This study investigated the influence of clinical pattern of care, utility, and contribution of pelvic examination aimed at diagnosing and managing bleeding in early pregnancy at three Canadian EDs. Methods: After obtaining informed consent, data were collected from adult women who were pregnant and from treating ED physicians using a structured questionnaire. We defined the change in management based on the initial clinical plan at the time of the initial physician assessment in the ED and any subsequent changes made after the pelvic examination was performed. Patient telephone follow-up was supplemented by linking with provincial administrative data for births. Univariable and multivariable binary logistic regression analyses were performed to identify factors associated with a change in patient management following pelvic examination in the ED. Results: Overall, 200 women were enrolled. The mean age was 31 years, patients had been bleeding for a median of 1 day and stayed in the ED for a median of 5 h. Of these, 166 (83.0%) received a pelvic examination, including speculum examination and/or bimanual palpation. Pregnancy outcome data were available for 192 pregnancies; 107 (56%) experienced a miscarriage. Factors significantly associated with a change in management after pelvic examination in the univariate logistic regression analysis were brown/dark-red bleeding per vaginam (physician determined), tachycardia, right lower quadrant tenderness, and bimanual palpation. In the multivariate logistic regression analysis, brown/dark-red bleeding per vaginam was independently associated with a reduced likelihood of a change in management after pelvic examination (aOR = 0.37; 95% CI: 0.14–0.98). Conclusion: Among women presenting to the ED with bleeding in early pregnancy prior to 20 weeks gestation, only brown/dark-red vaginal bleeding, potentially indicative of bleeding resolution, significantly independently influenced the baseline odds of a change in management after pelvic examination. Until the debate on the utility of pelvic examination in the ED for this presentation is resolved, physician preferences and shared decision making with patients should guide practice regarding speculum examination/bimanual palpation for the management of bleeding in early pregnancy. [ABSTRACT FROM AUTHOR]

Background: Research on incidence and characteristics of Out-of-Hospital Cardiac Arrest (OHCA) in the Middle East is limited. We assessed the incidence, prehospital characteristics, and outcomes of OHCA in Qatar, a Middle Eastern country. Subsequently, we performed gender-specific analysis. Methods: This was a retrospective examination of data obtained from the OHCA registry at Hamad Medical Corporation (HMC) in Qatar from 2017 to 2022. We included adults, non-traumatic, EMS-treatment OHCA. We calculated the incidence of adult OHCA and conducted descriptive analyses for prehospital characteristics, and prehospital outcomes presented by return of spontaneous circulation (ROSC). We evaluated gender differences in prehospital characteristics and ROSC using Student's t-test and the Chi-Square test as appropriate. Furthermore, we conducted a multivariable logistic regression analysis to investigate the correlation between gender and achieving ROSC. Results: We included 4,306 adult OHCA patients, with 869 (20.2%) being females. The mean annual incidence of adult OHCA was 27.4 per 100,000 population-year. Males had a higher annual incidence of OHCA than females. Among all cases, 36.3% occurred in a public location, 25.8% had an initial shockable rhythm, and 28.8% achieved ROSC. Males had a higher proportion of bystander CPR, arrests in public locations, and initial shockable rhythms. While unadjusted analysis showed no significant gender differences in achieving ROSC, adjusted analysis revealed that male gender was associated with higher odds of achieving ROSC (adjusted OR male vs. female 1.38, 95% CI 1.15–1.66, p < 0.001). Conclusions: Approximately 720 adults undergo non-traumatic OHCA in Qatar every year, with a higher incidence observed in males. Male gender was associated with higher odds of achieving ROSC. Further gender-specific research in OHCA intervention and outcome in the Middle East is required. [ABSTRACT FROM AUTHOR]

The association between self-assessed cold threshold (CT) and thermal insulation of clothing (Icl) was analysed in 283 poultry workers in Thailand. The mean CT was 13.5 °C (range − 28–29) and the mean Icl was 1.23 clo (range 0.35–2.21). The adjusted CT remained unchanged at low Icls (0.35 through 1.25 clo) but was estimated to increase by 14.8 °C at high Icls (1.25 through 2.21 clo). Overall, CT was higher by 2.4 °C (95% confidence interval [CI] 0.3–3.8) at high (≥ 1.25 clo) than that at low (< 1.25 clo) Icl, but this difference was modified by personal and work-related factors. The difference was 2.6 °C (CI 0.5–4.6) for older (30–57 y) compared to younger (18–29 y) participants, with an excess of 7.3 °C (CI 5.6–9.0) for low vs high educated participants, 2.6 °C (CI 0.5–4.8) for those doing heavy vs light work, 7.4 °C (CI 3.7–11.0) for alcohol consumers vs others, and 3.4 °C (CI 0.6–6.3) for smokers vs non-smokers. The differences were independent of personal characteristics and worksite physical conditions and were interpreted as increased cold sensitivity among subgroups with lesser stamina and poorer health. Sensitive worker subgroups should be identified, and their need for cold protection should be reviewed. [ABSTRACT FROM AUTHOR]

Background: Strength training (ST) primarily enhances physical fitness (e.g., muscle strength, power, speed) and bone density in female soccer players. Less information is available on the injury preventive effects of ST in female athletes. Accordingly, this study aimed to investigate the effects of a 12-week in-season ST on measures of physical fitness and injury occurrence in young elite female soccer players. Methods: Thirty elite female soccer players (15.4 ± 1.9 years; maturity offset + 2.3 ± 1.1 years) participated in this study, and were randomly assigned to a strength training group (STG, n = 14) or an active control (CG, n = 16) group. ST lasted twelve weeks and included full body muscle strengthening exercises using primarily weight machines at progressive intensities ranging between 40 and 85% of the one-repetition-maximum (1-RM). The CG practiced a traditional soccer training program. Overall, training volumes of the two groups were similar with a training load (rating of perceived exertion × time) of 1158.4 ± 67.7 arbitrary unity (AU) for the STG and 1188.8 ± 44.1 AU for the CG. Pre and post training, the following physical fitness tests were applied: dynamic muscle strength (relative [to body mass] and absolute 1-RM bench/leg press, lat-pull down), jump performance (countermovement jump [CMJ], squat jump [SJ], five-jump-test [5JT]), linear-sprint speed (5-m, 10-m, 30-m), change-of-direction speed (T-test with and without ball), sport-specific performance (Yo-Yo Intermittent Level1 [YYIRTL1], and repeated shuttle sprint ability [RSSA]). The injury rate per 1000-h exposure was monitored throughout the soccer season. Results: No significant baseline differences were observed between groups. Statistically significant group-by-time interactions were found for absolute (p < 0.001, d = 2.59) and relative 1-RM bench press (p < 0.001, d = 2.39), absolute 1-RM lat-pull down (p < 0.001, d = 1.68), and relative 1-RM leg press (p < 0.001, d = 1.72). Significant group-by-time interactions were observed for CMJ (p = 0.005, d = 1.27), RSSAmean (p = 0.007, d = 0.81), and RSSAtotal (p < 0.001, d = 1.90). Post-hoc tests indicated that the STG group demonstrated greater improvements in all tested variables compared to CG (1.2 < d < 2.5). However, no significant interaction effects were noted for measures of linear sprint speed and YYIRTL1 performance. Additionally, non-contact injuries during the season were significantly lower (p = 0.003, d = 1.31) in the STG (0.48/1000 h of exposure) than the CG (2.62/1000 h of exposure). Conclusions: Twelve weeks of an in-season ST resulted in larger physical fitness improvements and fewer injuries compared with an active control in elite young female soccer players. Accordingly, ST should be systematically applied in female soccer to enhance performance and prevent injuries. Key Finding: This study showed that the incorporation of 12 weeks of strength training with two weekly sessions during the soccer season improves anthropometric and body composition characteristics as well as measures of physical fitness in adolescent elite female soccer players. Strength training reduces the incidence of non-contact injuries in young female soccer players. The usage of strength training machines is safe in elite young female soccer players with no previous experience in weightlifting. [ABSTRACT FROM AUTHOR]

Background: Firearm purchasing records offer a potentially important administrative data source to identify individuals at elevated risk of perpetrating firearm violence. In this study, we describe individual, firearm, and transaction characteristics of purchasers in California who were arrested for a firearm-related violent crime (FRV) as compared to the general population of registered purchasers in the state. Methods: Relying on a dataset of all individuals with transaction records in California (1996–2021), linked to criminal records (1980–2021), we enrolled a cohort of individuals for whom we could capture the legal firearm purchase history. We identified those arrested for FRV post purchase, and using incidence density sampling, gender-matched cases to ten purchasers (controls) who remained "at risk" at the time the case was arrested. We focused on the purchase closest in time prior to the arrest ("index" purchase). We implemented conditional logistic regression and included models with controls for individual- and community-level demographics, as well as interactions between firearm and purchasing characteristics and criminal history. Results: The cohort included 1,212,144 individuals, of whom 6153 were arrested for FRV (0.5%). Cases were matched to 61,530 controls to form the study sample. The largest risk factor was a prior criminal history: purchasers had 5.84 times the risk of FRV if they had a prior arrest within three years of the index purchase (CI 5.44–6.27). Several transaction and firearm characteristics were also associated with FRV. For example, risk increased if the firearm was redeemed at a pawn shop (aIRR: 1.37, CI 1.05–1.77) and decreased if the transaction was a registered private party transfer (vs. retail purchase) (aIRR: 0.83, CI 0.76–0.90) or the firearm was a bolt action firearm (vs. semi-automatic) (aIRR: 0.64, CI 0.51–0.79). In the interaction models, most of the purchase and firearm features only remained significant among those with no criminal history. Conclusions: Given limited data on firearm transactions, there has been little research on whether the type of firearm an individual purchases or the nature of the purchase might serve as indicators of risk for FRV. We found several transaction and firearm features were associated with risk of FRV. Notably, these features provided little evidence of additional risk for those with a prior criminal record. [ABSTRACT FROM AUTHOR]

Introduction: There has been an advent in the use of Mobile Apps in the academic space. The pandemic hastened their usage, and forced us to rapidly innovate in order to meet the educational needs of our students. Also, Mobile Apps have been known to facilitate self-learning, make it enjoyable, and personalize the pace of learning of the individual. Given the level of skill-learning in Physiotherapy education, the use of Mobile Apps can pose a challenge, as well as offer an opportunity to explore its scope to enhance learning, and create innovative pedagogic strategies. There are a very few learning mobile apps that have been assessed in Physiotherapy education. Aim: To develop, establish content validity and internal consistency of a curriculum based App on the kinesiology of normal Gait for bachelor of physiotherapy students, and to evaluate the App with regards to use, quality, engagement, and overall experience. Materials & methods: In the first phase, a mobile app based on a bachelor of physiotherapy Gait curriculum was developed and validated using Delphi procedure, with 80% agreement criteria, by a group of experts. Subsequently, the App was rated by 200 users on: engagement, aesthetics, information, subjective quality. Results: The content validity index following 2 rounds of Delphi was found to be 0.88. Also, therapists found the App easy to use, and 80% gave it a rating of > 3 stars. Conclusion: Creating, designing, implementing, and evaluating the efficacy of a Gait App as a means to teaching the GAIT component to physiotherapy students was found to be appealing and beneficial. [ABSTRACT FROM AUTHOR]

The Lorenz curve portrays income distribution inequality. In this article, we develop three modified empirical likelihood (EL) approaches, including adjusted empirical likelihood, transformed empirical likelihood, and transformed adjusted empirical likelihood, to construct confidence intervals for the generalized Lorenz ordinate. We demonstrate that the limiting distribution of the modified EL ratio statistics for the generalized Lorenz ordinate follows scaled Chi-Squared distributions with one degree of freedom. We compare the coverage probabilities and mean lengths of confidence intervals of the proposed methods with the traditional EL method through simulations under various scenarios. Finally, we illustrate the proposed methods using real data to construct confidence intervals. [ABSTRACT FROM AUTHOR]

Background and Aims: Multi-ligament knee injuries (MLKI) are serious and challenging to manage. This study aimed to elucidate the impact of surgical timing on both early and long-term outcomes following an MLKI. Methods: A comprehensive search strategy was employed across PubMed, Scopus, Web of Science, and the Cochrane Library. Studies were identified using a combination of relevant keywords encompassing "multi-ligament knee injury," "knee dislocation," "reconstruction," "repair," "surgery," and "timing," and their synonyms, along with appropriate Boolean operators. Selection of articles (systematic reviews and meta-analyses) adhered to predefined inclusion and exclusion criteria. Furthermore, a meta-analysis was conducted utilizing data extracted from primary studies. Results: Early surgery for MLKI demonstrated a significant advantage over delayed surgery, reflected by significantly higher Lysholm scores (Mean Difference [MD] 3.51; 95% Confidence Interval [CI] 1.79, 5.22), IKDC objective scores (Mantel–Haenszel Odds Ratio [MH-OR] 2.95; 95% CI 1.30, 6.69), Tegner activity scores (MD 0.38; 95% CI 0.08, 0.69), and Mayer's ratings (MH-OR 5.47; 95% CI 1.27, 23.56). In addition, we found a significantly reduced risk of secondary chondral lesions (MH-OR 0.33; 95% CI 0.23, 0.48), lower instrumented anterior tibial translation in the early surgery group (MD −0.92; 95% CI −1.83, −0.01), but no significant difference was observed in the secondary meniscal tears, between the two groups. However, the early surgery group also exhibited a significantly increased risk of knee stiffness (MH-OR 2.47; 95% CI 1.22, 5.01) and a greater likelihood of requiring manipulation under anaesthesia (MH-OR 3.91; 95% CI 1.10, 13.87). Conclusion: Early surgery for MLKI improves function, and stability, and reduces further articular cartilage damage, but increases the risk of stiffness. Level of Evidence: IV. [ABSTRACT FROM AUTHOR]

Introduction: Multi-ligament knee injuries (MLKIs) are rare and complex knee lesions and are potentially associated with intra-articular injuries, especially meniscal tears. Understanding the meniscal tear patterns involved in MLKI can help the orthopedic surgeon treat these complex injuries. Objective: The purpose of this study was to describe the incidence, classification, and treatment of meniscal injuries in a cohort of patients with MLKIs and carry out an updated review of the evidence available. Materials and methods: Descriptive retrospective study. Patients with a history of reconstructive surgery for MLKI performed between 2013 and 2023 were included. Informed consent was obtained from all patients included in the study. Patient demographics, magnetic resonance imaging (MRI) study, and operative reports were reviewed. Groups were then formed based on ligament injury patterns. Meniscal tears were identified by MRI and through diagnostic arthroscopy for each patient. The association between meniscal lesions and injury patterns was calculated through Fisher's exact test. Agreement between the presence of meniscal tear on MRI and in diagnostic arthroscopy was measured using the kappa test. The sensitivity and specificity of MRI were calculated. We inferred the presence of a meniscal tear by injury pattern using the Agresti-Coull confidence interval. For the statistical analysis, a significance of 5% and a confidence interval of 95% were considered. Results: Seventy patients with MLKIs were included, with a mean age of 30.69 years (SD 10.65). Forty-seven patients had meniscal lesions (67.1%). Of them, 6 had only medial meniscus tears, 31 had only lateral meniscus tears, and 10 had lesions of both menisci, comprising 57 meniscal lesions in total. An anterior cruciate ligament (ACL) + medial collateral ligament/posteromedial corner (MCL/PMC) was the most common injury pattern (52.86% of all patients). Of these 37 patients, 78.38% had meniscal injuries, and most of them (68.97%) were only lateral meniscus injuries. The odds ratio (OR) of having a meniscal tear when having an ACL + medial-side injury was 4.83 (95% CI; 0.89–26.17). Patients with ACL + lateral-side injury pattern had meniscal tears in 42.86%. The lateral meniscus was involved in 100% of these patients. 62.5% of medial meniscus injuries were treated by meniscal repair, and 37.5% by partial meniscectomy. 58.54% of lateral meniscus injuries were treated by meniscal repair, and 39.02% by partial meniscectomy. Agreement calculated using the kappa test between MRI and diagnostic arthroscopy for medial meniscal lesions was 78.57%, and for lateral meniscal lesions was 84.29%. Conclusion: The ligament injury pattern and the side of the injured collateral ligament influenced the incidence and laterality of meniscal damage. ACL + medial-side injuries were shown to have significantly greater meniscal damage compared to other injury patterns. It is crucial to have a high index of suspicion, obtain a high-quality MRI, and arthroscopically evaluate any possible meniscal lesions in MLKIs. [ABSTRACT FROM AUTHOR]

Introduction: Needlestick and sharps injuries (NSSIs) represent an existential occupational hazard risk to orthopaedic surgeons during their career due to the interaction with various devices, instruments and bone fragments. Consequently, NSSIs have the potential to transmit infections such as Hepatitis B (HBV), Hepatitis C (HCV) and Human Immunodeficiency Virus (HIV) leading to serious illness. The purpose of this cross-sectional study was to identify the clinical settings predisposing orthopaedic surgeons to NSSIs and assess their adherence to safety protocols in the Indian context. Materials and Methods: An online cross-sectional survey of 618 orthopaedic surgeons in India, stratified by experience into two groups: under five years and with 5 years or more was undertaken. The data were collected via an expert-validated online questionnaire to evaluate demographic distribution, injury characteristics, knowledge of safety protocols, and adherence to these protocols. Descriptive statistics summarized the data, Chi-square tests assessed variable associations, and odds ratios were computed for significant variables. Ethical integrity was maintained via electronic informed consent and for confidentiality assurances. Results: The study revealed that orthopaedic surgeons with less than 5 years of clinical experience had higher risks for NSSIs as compared to those with 5 or more years of clinical practice. Conversely, the latter group was more susceptible to bone spike injuries and viral positive needlestick incidents. The analysis shows that whilst the more experienced practitioners displayed greater proficiency in the application of universal precautions and NSSI prevention, they were also less likely to report injuries, often due to discomfiture. Risk profiles were consistent across different practice settings and affiliations, regardless of experience level. Conclusion: This cross-sectional study reveals less experienced orthopaedic surgeons face higher risks of NSSIs, possibly due to inadequate education or awareness. More experienced practitioners encounter distinct risks, likely owing to long-term exposure and traditional practices. There is an immediate need to raise awareness of the potential risks of NSSIs, enhanced education, appropriate training, collaboration with the hospital risk management team and developing a culture of transparent reporting to mitigate these risks. The emphasis should be on reducing the incidence and fostering open reporting of NSSIs to protect clinicians and promote health safety. [ABSTRACT FROM AUTHOR]

Objective: The relationship between spontaneous osteonecrosis of the knee (SONK) and ipsilateral meniscus tear remains to be established, and the possible causes are clarified and summarized. Methods: We conducted a search in Pubmed, Web of Science, Embase, and the Cochrane Library to include all English articles published from the establishment of the database until April 2023. The odds ratio (OR) and 95% confidence interval (CI) were calculated to evaluate the relationship between SONK and ipsilateral meniscus lesions. Results: A total of 405 patients were included in eight articles, including 157 males and 248 females, with an average age of 63.94 years and an average BMI of 26.36 kg/m2. In patients with medial SONK, the prevalence of ipsilateral meniscus tear was 0.8982, 95% CI (0.7389, 0.9648), and the prevalence of ipsilateral posterior root tear was 0.6198, 95% CI (0.5169, 0.7118). The prevalence of ipsilateral meniscus tears in patients with lateral SONK was 0.2188, 95% CI (0.1150, 0.3711), and the prevalence of ipsilateral posterior root tears was 0.1667, 95% CI (0.1071, 0.2424). Conclusions: SONK is significantly associated with meniscus or root tears, which limit meniscus function and lead to changes in the stress environment between the knee and the tibiofemur, increasing the chance of incomplete fracture. We suggest that the expression of SONK can be replaced with subchondral insufficiency fracture of the knee. [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the impact of dapagliflozin on reducing major adverse cardiovascular events (MACE) and all-cause mortality in patients with COVID-19 and to assess whether it was associated with clinical improvement. Methods: Between March 2020 and July 2022, 446 diabetic patients hospitalized with COVID-19 were included in the study and were divided into two groups in terms of dapagliflozin use: 120 patients in the dapagliflozin group and 326 patients in the other oral antidiabetic (non-dapagliflozin) group. Results: Six (5%) deaths occurred in the dapagliflozin group and 58 (17.8%) in the non-dapagliflozin group (p=0.001). Lower rates of ICU admission were observed in the dapagliflozin group (8 (6.7%) vs. 67 (20.6%) patients) (p = 0.001). MACE occurred in 23 patients (19.2%) in the dapagliflozin group and 70 (21.5%) in the non-dapagliflozin group (p = 0.689). Higher age (p = 0.001) and higher urea (p = 0.019) were associated with increased risk of mortality. Dapagliflozin users had 3.937-fold lower risk of mortality (OR, 0.254; 95% CI, 0.093–0.697; p = 0.008). Multivariable logistic regression revealed that advanced age, active smoking, presence of peripheral artery disease, lower left ventricular ejection fraction, and glucose level were independently associated with MACE. Conclusion: We demonstrated that dapagliflozin treatment may be related with a reduced risk of mortality and lower ICU admission rates in diabetic patients hospitalized with COVID-19. Despite the limitations of the study, dapagliflozin could benefit COVID-19 patients with cardiometabolic risk factors, but further studies that control for our limitations are necessary. [ABSTRACT FROM AUTHOR]

Background: Association between liver cirrhosis (LC) and glucose intolerance has been known since long. Many studies in the past have attempted to explore the correlation of glucose metabolism disorders (GMD) with the severity of LC with mixed results (some favouring i.e. higher prevalence of GMD in more severe LC; others negating). This study was conducted to shed further light on the significance of this association. Objective: This study has been carried out with the aim of studying the correlation between GMD and the severity of LC, as determined by the Child-Turcotte-Pughe (CTP) score. Methods: 100 patients with LC admitted in medical wards were studied and tested with fasting plasma glucose (FPG), 2 h post-75 g oral glucose load plasma glucose (PPG), glycosylated haemoglobin (HbA1c) and fasting plasma insulin. They were categorized based on the severity of LC into CTP A, B or C class and then patients belonging to different classes were compared for the presence of GMD and insulin resistance (IR). Conclusion: Out of 100 patients, 6, 21 and 73 were respectively found as falling under CTP class A, B and C of LC. The frequency of diabetes mellitus (DM) was found to progressively increase with worsening grade of cirrhosis (17%-A, 24%-B and 27%-C), however this was not significant (p value 0.82). The p values for IR, GMD (pre-diabetes or DM), pre-diabetes (pre-DM) were 0.629, 0.382 and 0.189 respectively. To conclude, development of GMD and IR may be independent of the severity of LC. However more studies may be required to further study this association. [ABSTRACT FROM AUTHOR]

Objective: We studied the presence of psychological stress in patients with type 2 diabetes (T2D) and if could be attributed to the consumption of a pro-inflammatory diet. We evaluated the inflammatory potential of the habitual Mexican diet, addressed by tools with an approach to collecting information on e-Health. Methods: In this cross-sectional analytic study of 238 Mexican adults with T2D, the profile of the inflammatory diet was obtained by the Dietary Inflammatory Index (DII), and the presence of psychological stress by the Diabetes Distress Scale-17 (DSS) was assessed. Multivariable logistic regression analysis was performed to estimate the association between diabetes stress and DII score. Sensitivity analysis was performed by Energy–Density Dietary Inflammatory Index (E-DII). Results: We demonstrated that there is an association between a profile of stress and high-inflammatory values of the DII score after adjustment for potential confounders (OR 2.40, 95% CI 1.2, 4.6). Conclusion: Using e-Health through web-based tools to collect information showed benefits of the application as a method of dietary assessment. We provide evidence showing that better values of the DII score and physical activity may play a protective role against the presence of psychological stress; DII and E-DII scores qualify and label habitual diet into pro and anti-inflammatory and are associated with psychological stress in T2D. [ABSTRACT FROM AUTHOR]

Background: Diabetic foot is a global threat to public health, as it can lead to infections and amputations and cause significant pain and economic costs for patients. Diabetic foot patients in northern China have more severe local ulcers, worse prognosis, and longer disease duration. Objective: This study assessed the foot risk levels and foot care knowledge and behavior status of people with diabetes with different foot risk levels, and investigated the factors that influence the occurrence of high-risk foot in diabetes. Methods: This cross-sectional survey included 410 hospitalized people with diabetes. Demographic and disease-related data and foot risk stratification status were collected using investigator-designed questionnaires. Foot care knowledge and behavior questionnaires were also used. Results: Among the 410 participants, a total of 367 cases were classified as high-risk feet, among which 135 cases were rated as grade 1, 202 cases grade 2, and 30 cases grade 3. Foot care knowledge surveys revealed low scores in the areas of shoe and sock selection, foot and footwear examination, and management of foot problems. Foot care behavior surveys showed low scores in the areas of foot and footwear examination, management of foot problems, and foot injury risk behavior. One-way ANOVA revealed significant differences in foot care behaviors among patients with different foot risk classifications (p < 0.05), while no significant differences were observed in foot care knowledge scores. Multivariate logistic regression analysis showed that age, history of cerebrovascular disease, and foot care behavior scores were factors influencing the occurrence of high-risk foot in people with diabetes. Conclusion: The results of this study showed a high prevalence of high-risk foot in diabetics; The knowledge and behavior of foot care in diabetics with different foot risk levels were both at a moderately low level; There were differences in foot behavior scores among patients with different foot risk classes, but, counter-intuitively, no significant differences in foot care knowledge. The study found that advanced age, history of cerebrovascular disease, and low foot care behavior scores are risk factors for high-risk foot in diabetes. Therefore, it is necessary to screen patients with diabetes for high-risk feet and implement targeted interventions according to the results. [ABSTRACT FROM AUTHOR]

Objective: Tropical diabetic hand syndrome (TDHS) is rarely described and recognized in the literature as a complication in people with diabetes, and Mexico has high incidence rates of diabetes mellitus II (DMII). The minor or major amputation of the arm represents a physically and economically significant morbidity problem in patients. To optimize the diagnosis and treatment, in this work, we identify prognostic factors and their association with the severity of TDHS and the need for amputation in patients with diabetes mellitus and hand tissue infection. Methods: A total of 55 patients with a confirmed diagnosis of DMII with soft tissue infection in the hand referred to the plastic and reconstructive surgery department were studied for their evaluation and treatment. We analyze sociodemographic and clinical factors and follow-up of remission and recovery in limb functions. Results: In our study, we identified factors associated with amputation such as schooling under 6 years (OR: 21.98, confidence interval (CI): 1.21–3.98, p = 0.003), body mass index ≥ 20 (OR: 0.07, CI = 0.003–1.41, p = 0.031), and history of amputation (no upper limb) (OR: 5.9, CI = 1.11–32.1, p = 0.032). Furthermore, people with TDHS requiring amputation had slightly higher glycated hemoglobin (Hb1Ac) ≥ 10% (OR: 2.36, CI = 0.62–8.98, p = 0.338), and the risk of death was also increased (OR: 3.4, CI = 0.355–32.6, p = 0.288), although these outcomes did not reach statistical significance. Conclusions: Risk factors for amputation as a treatment of THDS are directly linked to lower schooling status, poor nutrition/low weight, as well as previous amputation procedures in patients. These data will help to establish a timelier evaluation and management in patients with suspected THDS. [ABSTRACT FROM AUTHOR]

Background: Omentin-1 has been acknowledged as an anti-inflammatory and insulin-sensitizing marker, which is mainly expressed in adipose tissue. Exercise training is a therapeutic intervention that can possibly improve and modify circulating Omentin-1 levels. Objective: To determine the effects of exercise training on circulating Omentin-1, glycemic control, and body composition in adult population. Data sources: Four electronic databases and reference lists of included articles were searched until February 5, 2023. The effect size of outcomes was summarized by calculating the mean difference (MD) with 95% confidence interval (CI). Results: Ten RCTs comprising 385 participants were included. The overall model revealed that exercise training increased Omentin-1 compared to the control (MD = 3.57 ng.ml; 95% CI, 1.80 to 5.34 ng.ml; p < 0.001). Subgroup analysis by exercise modalities revealed significant increases in Omentin-1 after isolated aerobic (p = 0.002) and resistance (p < 0.001) training but not after combined training. Subgroup analysis by sex indicated a significant improvement of Omentin-1 in women (p = 0.015) and men (p = 0.007). Furthermore, a significant increase was found in both healthy (p = 0.035) and non-healthy (p = 0.002) participants. Analysis of other outcomes indicated that exercise training significantly reduced glucose, insulin, insulin resistance, body weight, body mass index, and body fat, as well as improved lipid profiles. Conclusion: These findings reveal that isolated aerobic and resistance exercises resulted in an increase in serum levels of Omentin-1 in adults. More high-quality studies are required to clarify the mechanisms underlying the influence of exercise training on Omentin-1 concentrations. [ABSTRACT FROM AUTHOR]

Objective: The triglyceride glucose (TyG) index and obesity are significantly closely related to the incidence of nonalcoholic fatty liver disease (NAFLD). The study aimed to investigate the relationship among the TyG index and its related parameters [TyG-waist circumference (WC) and TyG-body mass index (BMI)] with NAFLD. Methods: This was a cross-sectional study involving 8401 subjects who underwent a health examination in Karamay, Xinjiang Province, China. TyG, TyG-WC, TyG-BMI were calculated with the established formula. NAFLD was diagnosed and classified by ultrasonography. Results: The prevalence of NAFLD was markedly increased with increasing levels of TyG, TyG-WC and TyG-BMI. Logistic regression analysis suggested that WC, BMI, TyG, TyG-WC and TyG-BMI were independent risk factors for NAFLD. In receiver operating characteristic (ROC) analysis, TyG-BMI showed the largest area under the ROC curve (AUC) for the detection of NAFLD (0.856, 95% confidence interval: 0.848 ~ 0.865), and the results of sex analysis were consistent. TyG-BMI values of 176.69 (sensitivity: 86.9%, specificity: 68.1%), 193.02 (sensitivity: 73.8%, specificity: 73.6%) and 167.73 (sensitivity: 86.3%, specificity: 74.4%) were the optimal cutoff points to predict NAFLD in all participants, males and females, respectively. Conclusions: This study demonstrated that TyG and its related parameters are significantly correlated with NAFLD. TyG-BMI is an effective predictor or clinical marker for identifying NAFLD. [ABSTRACT FROM AUTHOR]

Objective: Diabetes is a non-communicable disease, and the prevalence of diabetes is higher in low and middle-income countries. In India, diabetes prevalence has been observed, with some regional variations across the states. This study analyses the current scenario of diabetes in India among women of the reproductive age group between 15 to 49 years. Methods: For conducting this study, data were gathered from the fifth round of the National Family Health Survey (2019–2021). It is a two-stage cross-sectional stratified sampling survey that employs the probability proportional to size methodology. A total of 6,59,010 individual reproductive-age women have been sampled for this study. Data were analyzed using the Stata version 14 software. A binary logistic model was carried out to know the relationships between diabetes and various socioeconomic and demographic variables. In addition, the adjusted odds ratio was reported with a 95% confidence interval. Results: The result shows that about 1.65% of reproductive age group women in India are diabetic with the highest in Goa (4.09%) and the lowest in Nagaland (0.81%). Further, in urban areas, the women's diabetes rate is 16% higher than in the rural areas. Besides, diabetes is strongly correlated with obese reproductive age-group women who are above 35 years and reside in urban areas with higher socioeconomic status. Conclusion: This study suggests that there is an urgent need for frequent monitoring of glycated haemoglobin (HbA1c). Besides, a spatially-optimized target-oriented policy framework is needed instead of a comprehensive national policy to tackle diabetes problems in the country. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to assess the effects of sodium-glucose co-transporter inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase-4 inhibitors (DPP4i) on individuals subjected to diabetes and COVID-19. Methods: PubMed, Embase, Web of Science, and Cochrane Library were systematically searched to cover studies (except for case reports and review studies) published until August 30, 2022. The primary outcome was the mortality of people with diabetes and COVID-19. The secondary outcomes comprised the requiring intensive care unit (ICU) admission and mechanical ventilation. Two reviewers independently screened studies, abstracted data, and assessed risk-of-bias. Furthermore, the network meta-analyses (NMA) were conducted. Results: A total of 12 trials were involved in the analysis. The OR and 95% CI of mortality for SGLT2i compared with SGLT2i + GLP-1RA and DPP4i reached 0.41 (0.17,0.97) and 0.69 (0.49,0.98), respectively. The OR and 95% CI of requiring mechanical ventilation for SGLT2i compared with the DPP4i reached 0.85 (0.75,0.97). Conclusions: As revealed by the result of this study, SGLT2i is associated with the lower mortality rate in people with diabetes and COVID-19 among novel glucose-lowering drugs. And SGLT2i is linked to lower requiring mechanical ventilation. These findings can have a large impact on clinicians' decisions amid the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

While the Taguchi capability index developed by Chan (J Qual Technol 20(3):162–175, 1988) takes the process targeting issue into consideration, it fails to account for processes with asymmetric tolerances, which are common in practice. Thus, Chen (Int J Reliab Qual Saf Eng 6(4):383–398) modified this index to include processes with asymmetric tolerances. This index is an important tool for the assessment of quality characteristics with asymmetric tolerances, which are common in practice. As the probability density function of the index is complex, statistical inference can be fairly difficult for quality or process engineers. Furthermore, sample sizes are often small in practice to increase decision-making efficiency, but this can decrease assessment accuracy. To address this issue, we employed a mathematical programming approach to make it more convenient for quality or process engineers to derive the upper confidence limit of the index. We also adopted the suggestion put forward by previous studies to incorporate historical data or expert experience in confidence-interval-based fuzzy testing. The proposed approach therefore has increased assessment accuracy, is convenient to apply in practice, and meets the need for swift responses. [ABSTRACT FROM AUTHOR]

Introduction: Niraparib first-line maintenance (1LM) therapy has demonstrated clinical benefit for patients with ovarian cancer (OC) in clinical trial and real-world settings, but data on factors associated with real-world patient outcomes remain limited. This analysis identified patient characteristics associated with time to next treatment (TTNT), a proxy for real-world progression-free survival, in patients with OC treated with 1LM niraparib monotherapy. Methods: This retrospective observational study used a USA nationwide electronic health record-derived deidentified database and included adult patients diagnosed with OC who initiated 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Patients were followed until the earliest occurrence of last clinical activity, death, or end of study period. TTNT was measured from 1LM niraparib initiation to the start of second-line treatment or death. Cox proportional hazards models assessed univariable and multivariable associations between baseline characteristics and TTNT. Results: Of 7872 patients diagnosed with OC, 526 met the eligibility criteria and were included in this analysis. Median (IQR) duration of follow-up was 14.1 (7.4–23.6) months. In univariable analyses, age, BRCA/homologous recombination deficiency (HRD) status, socioeconomic status, stage at initial diagnosis, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT and were introduced into the multivariable model with other clinically relevant variables. In the multivariable analysis, BRCA/HRD status, cytoreductive surgery type, and residual disease status were significantly associated with observed TTNT after covariate adjustment. Conversely, age, Eastern Cooperative Oncology Group performance status, disease stage, niraparib starting dose status, and first-line bevacizumab use were not associated with observed TTNT. Conclusion: This real-world, retrospective, observational analysis offers valuable insights on prognostic factors associated with TTNT in patients with OC treated with 1LM niraparib monotherapy after first-line platinum-based chemotherapy. Future studies are needed to examine how additional patient characteristics associated with clinical outcomes may guide treatment decisions and improve outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of multiple myeloma (MM) has been transformed by novel therapies, including CD38 monoclonal antibodies (mAbs), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), resulting in increasing numbers of patients who are triple-class exposed (TCE; exposed to ≥ 1 drug in each class). Many patients are penta-exposed (PE; ≥ 2 IMiDs, ≥ 2 PIs, and a CD38 mAb), some are triple-class refractory (TCR), and some are PE and TCR (PE-TCR). Data on real-world outcomes in elderly patients with MM across this spectrum of exposure are limited. Methods: Data from the Medicare Chronic Conditions Warehouse Database from November 2006–December 2020 were used to examine cohorts of TCE, TCR, PE, and PE-TCR patients. Outcomes were assessed from the start of the index line of therapy (LOT), defined as the first LOT after becoming TCE or PE. Results: A total of 2830 TCE, 1371 TCR, 1121 PE, and 774 PE-TCR patients were identified. Pomalidomide was the most frequently used medication for the index LOT in all cohorts (32.6% [PE-TCR] to 43.3% [TCR]). The most frequently used regimens for the index LOT were pomalidomide plus daratumumab for TCE (17.2%) and PE (7.0%), pomalidomide plus carfilzomib for TCR (10.3%), and pomalidomide plus elotuzumab for PE-TCR (7.4%). Median time to discontinuation (TTD) ranged from 4.2 (PE-TCR) to 6.9 (TCE) months, and overall survival (OS) ranged from 13.0 (TCR) to 15.9 (PE) months. Healthcare resource utilization (HRU) was lowest for TCE and highest for PE-TCR patients. Mean monthly healthcare costs (HCC) ranged from $23,091 (TCE) to $24,412 (PE-TCR). MM medications represented 66.2% (PE-TCR) to 72.8% (TCE) of costs. Conclusions: In this study across a spectrum of Medicare TCE patients, there was heterogeneity in treatment regimens, suggesting no standard of care. TTD and OS were short, and HRU and HCC were high. These results underscore the potential for new therapies in this population. [ABSTRACT FROM AUTHOR]

Introduction: This study evaluated the pharmacokinetic (PK) equivalence between BP02 (a proposed trastuzumab biosimilar) and the reference trastuzumab approved in the EU (EU-trastuzumab) and the US (US-trastuzumab). Methods: In this phase 1, double-blind, parallel-group trial, 111 healthy male volunteers were randomized 1:1:1 to receive a single 6-mg/kg intravenous infusion of BP02, EU-trastuzumab, or US-trastuzumab and were evaluated for 78 days. Serum drug concentration–time data were analyzed by non-compartmental methods. The PK similarity of BP02 to the two reference products, and between EU-trastuzumab and US-trastuzumab, was determined using the standard 80–125% bioequivalence criteria. Results: Baseline demographics for the 111 subjects with evaluable pharmacokinetics were similar across all treatment groups. PK profiles were similar for the three products. The 90% confidence intervals (CIs) for the ratios of area under the serum concentration–time curve (AUC) from the time of dosing to infinity (AUC0-inf), AUC from the time of dosing until the time of the last quantifiable concentration (AUC0-t), and peak serum concentration of trastuzumab (Cmax) were within 80% to 125% for all three pairwise comparisons. Adverse events (AEs) were similar across all arms, with treatment-related AEs reported by 73.0%, 73.0%, and 89.2% of the subjects in the BP02, EU-trastuzumab, and US-trastuzumab groups, respectively. The most common AEs were headache, infusion-related reactions, and upper-respiratory-tract infections. Four subjects—three in the US-trastuzumab group and one in the BP02 group—discontinued the study due to AEs. All post-dose samples except for two tested negative for anti-drug antibodies. Conclusion: This study demonstrates the PK similarity among BP02, EU-trastuzumab, and US-trastuzumab. The safety and immunogenicity profiles observed for the three products in this study are consistent with previous reports for trastuzumab. Trial Registration: ANZCTR number: ACTRN12621000573853. [ABSTRACT FROM AUTHOR]

Introduction: A dynamic molecular biomarker that can identify early efficacy of immune checkpoint inhibitor (ICI) therapy remains an unmet clinical need. Here we evaluate if a novel circulating tumor DNA (ctDNA) assay, xM, used for treatment response monitoring (TRM), that quantifies changes in ctDNA tumor fraction (TF), can predict outcome benefits in patients treated with ICI alone or in combination with chemotherapy in a real-world (RW) cohort. Methods: This retrospective study consisted of patients with advanced cancer from the Tempus de-identified clinical genomic database who received longitudinal liquid-based next-generation sequencing. Eligible patients had a blood sample ≤ 40 days prior to the start of ICI initiation and an on-treatment blood sample 15–180 days post ICI initiation. TF was calculated via an ensemble algorithm that utilizes TF estimates derived from variants and copy number information. Patients with molecular response (MR) were defined as patients with a ≥ 50% decrease in TF between tests. In the subset of patients with rw-imaging data between 2 and 18 weeks of ICI initiation, the predictive value of MR in addition to rw-imaging was compared to a model of rw-imaging alone. Results: The evaluable cohort (N = 86) was composed of 14 solid cancer types. Patients received either ICI monotherapy (38.4%, N = 33) or ICI in combination with chemotherapy (61.6%, N = 53). Patients with MR had significantly longer rw-overall survival (rwOS) (hazard ratio (HR) 0.4, P = 0.004) and rw-progression free survival (rwPFS) (HR 0.4, P = 0.005) than patients with molecular non-response (nMR). Similar results were seen in the ICI monotherapy subcohort; HR 0.2, P = 0.02 for rwOS and HR 0.2, P = 0.01 for rwPFS. In the subset of patients with matched rw-imaging data (N = 51), a model incorporating both MR and rw-imaging was superior in predicting rwOS than rw-imaging alone (P = 0.02). Conclusions: xM used for TRM is a novel serial quantitative TF algorithm that can be used clinically to evaluate ICI therapy efficacy. [ABSTRACT FROM AUTHOR]

Introduction: Biological monoclonal antibodies play a pivotal role in cancer treatment, with biosimilars significantly enhancing their accessibility. In Brazil's ethnically diverse setting, real-world evidence is crucial for assessing the effectiveness and applicability of these therapies in routine clinical practice. Methods: We performed a multicentric, observational, prospective real-world study on biosimilar trastuzumab-dkst for adjuvant treatment of early HER2-positive breast cancer in Brazilian patients. Data were collected using a case-report form. Results: Of the 176 recruited, we present data from the first 59 patients (mean age 51.7 ± 12.9 years) who had completed treatment with trastuzumab-dkst. The mean time from diagnosis to the first adjuvant treatment with trastuzumab-dkst was 5.5 ± 2.7 months. Of the patients, 59% of patients achieved at least a 30-month follow-up. The 31.7-month invasive disease-free survival rate (IDFS) was 94.5% (95% CI 83.9–98.2%) and median IDFS was not achieved, since only three patients had invasive disease recurrence. The overall survival rate was 100% until the last assessment. The observed adverse events were similar to those presented by other studies using biosimilar or reference trastuzumab. Four serious adverse events (8.5%) were observed. A reduction in left ventricular ejection fraction of at least 10% was observed in 16.9% of participants. There was no treatment interruption, and three participants (5.1%) had their trastuzumab-dkst dose reduced. Conclusion: Our study reinforces the existing pivotal data, underscoring the real-world efficacy and safety of biosimilar trastuzumab-dkst in the adjuvant treatment for early HER2-positive breast cancer. The preliminary long-term effectiveness and safety data we present further validate trastuzumab-dkst's role as a cost-saving alternative in oncological care. These findings have important implications for improving patient access to crucial treatments and for the more efficient use of healthcare resources. ClinicalTrials.gov Registration: NCT03892655. [ABSTRACT FROM AUTHOR]

Introduction: Hepatic visceral crisis (VC), characterized by a rapid total bilirubin increase with disease progression, poses a life-threatening risk in advanced breast cancer (ABC). International consensus guidelines define VC and touch on impending VC (IVC). Limited data exist on systemic treatments for hepatic VC/IVC. This study explores the safety and efficacy of cisplatin monotherapy in patients with Human Epidermal Growth Factor Receptor 2- negative breast cancer (BC) and hepatic IVC/VC. Methods: In this retrospective single-center cohort study data of patients treated with cisplatin monotherapy (60–80 mg/m2, every 3–4 weeks) between 2016 and 2023 at a reference Cancer Centre in Southern Poland were analyzed. Results: 33 female patients (24/33 hormonal-positive) with the mean age 53.84 years were included. Participants progressed on median 2 prior palliative systemic treatment lines. In 10/23 patients hepatic VC and in 23/33 IVC (rapid, symptomatic liver progression; extensive liver involvement; alanine or aspartate aminotransferase > 2 × normal limit; significant increases in lactate dehydrogenase, alkaline phosphatase, or gamma-glutamyl transferase) were identified. Median progression-free survival was 1.87 months and median overall survival 2.67 months. 33% of the patients presented stable disease or partial response. Eight patients experienced adverse events grade ≥ 3: in five the dose of cisplatin was reduced; two stopped the treatment. Conclusion: Due to the hepatotoxicity of BC-active drugs, specific recommendations for systemic treatment are scarce. Our study explored cisplatin's potential use, finding it to be a viable option in patients with performance status 0 or 1 experiencing hepatic IVC/VC, irrespective of liver function parameters and other factors. [ABSTRACT FROM AUTHOR]