This phase I/II study evaluated the capacity of tumor microenvironment (TME) gene engineering by intratumoral injection of a viral vector encoding a designed CD40L and 4-1BBL combined with intravenous atezolizumab (anti-PD-L1 antibody) to induce immune activation in 24 patients with stage IV malignant melanoma refractory to PD-1 inhibition. Primary objective was tolerability. Tumor response, pharmacokinetics, and biomarker evaluations were secondary. Treatment was well-tolerated in both dose cohorts (1×10¹¹ and 5×10¹¹ viral particles). Th1 immune biomarkers was increased in the TME (NanoString) as well as in blood (Olink). In long-term survivors, we observed increased markers for T cell fitness and for the immunoproteasome. The overall response rate was 17% accordingly to RECIST 1.1 and disease control was noted in 54%. Forty-six percent of patients were still alive two years post enrollment. The lower dose showed very encouraging results with a median progression-free survival of 9.7 months and median overall survival of 26.3 months (post-hoc analyses). In conclusion, TME gene engineering may have re-sensitized refractory patients to checkpoint treatment or acted alone to control tumor growth. The small sample size and single arm design limits effect interpretation but the data shows promise for continued clinical investigation. Study registration: NCT04123470.

COVID-19 severity is strongly associated with hyperinflammation. Cyclosporine A (CSA), an interleukin-2 inhibitor with immunomodulatory and antiviral activity, has been proposed as a potential adjunctive therapy. This study evaluated the safety and efficacy of CSA in patients with moderate to severe COVID-19. We conducted A randomized, open-label phase III trial was conducted involving 66 patients with COVID-19. Participants were assigned to one of two groups: the CSA group (n = 23), receiving 6 mg/kg/day for 7-14 days, and a standard treatment group (n = 43). Clinical improvement (WHO ordinal scale) was the main goal, with C-reactive protein (CRP), ferritin, interleukin-6 ( IL-6), and D-dimer, and safety monitoring for 28 days as secondary outcomes significant differences in enrolment. The time to clinical improvement was significantly shorter in the CSA group (4.3 ± 1.0 vs. 5.1 ± 2.3 days; p = 0.025). Oxygen supplementation was used in 7 patients (30.43%) versus 12 patients (27.91%) in the standard group, with a p-value of 0.828. No significant differences occurred in the WHO ordinal scale, advanced respiratory support, or mortality. No secondary infections occurred. CSA improved oxygen saturation and reduced CRP and IL-6; differences in saturation at day 14 were not significant. D-dimer and ferritin levels were lower at day 14, with no differences observed at day 7. Cyclosporine did not significantly improve ordinal scale outcomes. However, it was associated with a shorter time to clinical improvement and favorable modulation of inflammatory markers in patients with COVID-19 and cytokine storm, without major safety concerns.

Type IV sleep monitors offer a low-burden option for obstructive sleep apnea (OSA) screening, yet their accuracy is often limited by motion artifacts and variability in signal-processing methods. The PM50-B is a wrist-worn Type IV device that combines high-sampling-rate (200 Hz) photoplethysmography (PPG)-based oximetry with wrist actigraphy to reduce motion artifacts and employs an adaptive SpO₂ waveform-based desaturation detection algorithm. This study aimed to validate the diagnostic performance of the PM50-B against reference sleep studies.

In this prospective observational study, adults with suspected OSA underwent simultaneous overnight recording with the PM50-B and a reference test: in-laboratory polysomnography (Type I), unattended polysomnography (Type II), or Type III home sleep apnea testing (HSAT). Oximetry and actigraphy signals were processed using a standardized workflow incorporating motion-artifact attenuation, signal stabilization, and sleep-wake estimation. From the SpO₂ signal, hypoxemia metrics were derived, including the oxygen desaturation index ODI2.5_5 (≥ 2.5% desaturation lasting ≥ 5 s/h of total sleep time), cumulative time with SpO₂ < 90% and < 95% (CT90, CT95), and lowest SpO₂. Agreement with the reference apnea-hypopnea index (AHI) was assessed using intraclass correlation coefficients, and diagnostic accuracy was evaluated at clinically relevant AHI thresholds.

A total of 475 participants were analysed (Type I, n = 37; Type II, n = 32; Type III, n = 406). ODI2.5_5 showed moderate-to-good agreement with AHI (ICC = 0.710) and good discrimination for moderate-to-severe OSA (AHI ≥ 15 events/h), with an under the curve (AUC) of 0.925 (sensitivity 81.20%, specificity 91.00%). Diagnostic performance was consistent across reference modalities (AUC range, 0.928-0.983).

The PM50-B provides clinically acceptable accuracy for OSA screening when combined with a standardized signal-processing approach, particularly in comparison with Type III HSAT. ODI2.5_5 emerged as the strongest diagnostic metric, while CT90, CT95, and lowest SpO₂ provided complementary characterization of nocturnal hypoxemia.

This study explored the feelings of nurses occupationally infected with COVID-19 during the late pandemic phase in Japan, from diagnosis to return to work, to provide suggestions for safe and continuous employment. Semi-structured interviews were conducted among 11 nurses infected during the late phase of the pandemic (August 2022 to February 2023). The data were analyzed using a qualitative inductive approach. At diagnosis, nurses experienced shock and a strong sense of guilt and self-blame arising from the feeling of being blamed by others. Negative emotions during the infection period influenced postreturn feelings, leading to distrust stemming from insufficient infection control measures and a desire to leave their workplace. Conversely, gratitude for the support from managers and colleagues during the recuperation period fostered their determination to return. Furthermore, a sense of achievement, such as improved nursing expertise and reaffirmation of professional values, facilitated a positive transformation of the infection experience, supporting work motivation. These findings suggest that managers and colleagues recognize the importance of alleviating nurses' self-blame, improving environments, and organizational support, enabling nurses to maintain achievement by reframing their experiences positively.

Since 1985, the international healthcare community has recommended the ideal rate of caesarean section (CS) to be 10%-15% at the national level. The literature has reported that overused CS without necessary medical indications can be harmful to both maternal and child health. To generate evidence to support policy on CS, this study evaluated the trend over time of CS in Thailand during January 2016 to October 2021 (which included the COVID-19 pandemic period) and explored predictors of CS use.

This study was a retrospective secondary data analysis of de-identified hospitalisation data under the Universal Coverage Scheme (UCS) from the National Health Security Office's e-Claims database. Descriptive analyses were conducted to explore the number and rate of CS over time and across different characteristics (ie, age, hospital type, COVID-19 status and delivery day) including a multivariable logistic analysis to explore predictors of CS. Interrupted time series analysis was adopted to investigate the effect of the COVID-19 pandemic on CS rate.

569 321 CS cases under UCS from 2016 to 2021.

The results showed an increasing trend of CS rate, from 30% in January 2016 to 35% in October 2021. Both clinical (eg, medical indication and age) and non-clinical (eg, region and day of delivery) factors were significantly associated with CS. Furthermore, the COVID-19 pandemic had no significant effect on CS rate (level: -0.0016, 95% CI -0.0085 to 0.0053, p=0.66).

This study highlighted an increasing trend of CS in Thailand and could present supportive evidence that Thailand might have been facing an overuse of CS. More awareness and actions are warranted to ensure the movement towards reduction of unnecessary CS in Thailand.

During 2024, the number of pandemic-prone and epidemic-prone disease outbreaks worldwide was estimated at 301. The data highlight a shift in disease outbreak patterns, with a decline in the number of countries reporting public health events of concern linked to COVID-19 and a rise in those reporting outbreaks of viral diseases transmitted by vectors.About 90% of the outbreaks in 2024 were associated with COVID-19, dengue, yellow fever, Oropouche virus disease and influenza (linked to identified zoonotic or pandemic influenza virus). Although disease outbreaks can affect any country anywhere, they tend to disproportionately occur in countries facing many other socio-economic development, climatic and humanitarian challenges. In this regard, sub-Saharan Africa and the subregion of Latin America and the Caribbean-home to just 23.3% of the world's population-reported the highest number of disease outbreaks in 2024 with about 57% of the total. Particularly, the sub-Saharan Africa region has been the site of nearly 32% of recorded outbreaks since 1996. Future research should include efforts to improve the quality and availability of disease outbreaks data-particularly in the most exposed or vulnerable regions-and to promote the scientific use of such information for foresight purposes and for forecasting future health events of concern to support anticipatory action.

Health workers (HWs) set an example for vaccine recipients, convey vaccine benefits and risks and interface with patients at increased risk for complications in pandemic settings. We explored HWs' acceptance of and recommendation for COVID-19 vaccine with and without previous receipt of seasonal influenza vaccine (SIV) in nine countries.

In 2023-2024, cross-sectional surveys among HW were conducted in Bangladesh, Cote d'Ivoire, Ghana, Laos, Lebanon, Morocco, Philippines, Thailand and Tunisia. Country researchers used a standard protocol and questionnaire to assess beliefs, perceptions and acceptance around SIV and COVID-19 vaccine and likelihood of recommending these vaccines to patients. Pooled findings were stratified by the presence or absence of a national HW SIV recommendation. Generalised mixed effects models were used to characterise the relationship between receipt of SIV and COVID-19 vaccine acceptance and recommendation, adjusting for WHO region, sex and duration of employment.

Our analysis included 12 296 HWs from nine countries representing four WHO regions: African, Eastern Mediterranean, Southeast Asian and Western Pacific. Five countries had a national HW SIV recommendation (61% of HWs surveyed) prior to COVID-19 vaccine introduction. More than 90% of HWs reported completing the COVID-19 vaccination series, whereas intention to continue receiving annual COVID-19 vaccine was lower (61%). HWs who received SIV in the last season compared with those who did not were more likely to have received one or more COVID-19 booster doses (adjusted OR (aOR) 2.63, 95% CI 2.27 to 3.04) and to have recommended COVID-19 vaccine to patients (aOR 1.53, 95% CI 1.29 to 1.82).

Prior experience with SIV was associated with HW behaviour and recommendations regarding COVID-19 vaccination. Intention to continue receiving COVID-19 vaccines remains a challenge; ongoing training and education for vaccination staff could be beneficial. HWs play a critical role in the successful delivery of new and existing vaccines, particularly in a pandemic setting.

Early evidence suggested an increase in child maltreatment during the COVID-19 pandemic. We sought to assess changes in the incidence rate of hospital admission for maltreatment among children younger than 2 years during the COVID-19 pandemic.

We conducted a pan-Canadian population-based interrupted time-series analysis from Apr. 3, 2016, to Mar. 25, 2023. We obtained administrative health data from the Canadian Institute for Health Information and the Institut national d'excellence de santé et services sociaux for all Canadian provinces and territories. The primary exposure was the COVID-19 pandemic period compared with the prepandemic period. The primary outcome was hospital admission for child maltreatment, and the secondary outcome was intensive care unit (ICU) admission for the same diagnosis. We compared incidence rates between the prepandemic and COVID-19 pandemic periods.

A total of 1518 hospital admissions for maltreatment occurred among children younger than 2 years. We found a 31% reduction in hospital admissions over 16 weeks at the beginning of the pandemic (adjusted rate ratio 0.69, 95% confidence interval [CI] 0.58 to 0.83) and a 56% reduction in ICU admissions (adjusted rate ratio 0.44, 95% CI 0.25 to 0.78). The rate of hospital admission returned to baseline, but the rate of ICU admission increased following the 16-week period of restricted health care access (adjusted rate ratio 1.80, 95% CI 1.23 to 2.63).

Initial public health measures and restricted health care access during the pandemic were associated with decreased rates of hospital admission for child maltreatment. We found no sustained reduction in overall hospital admission rates throughout the remaining pandemic period, but admissions to ICU increased. Our findings suggest that public health measures during the pandemic resulted in decreased detection of child maltreatment and possibly increased severity of cases involving hospital admission, suggesting a need for greater attention to identification and treatment of child maltreatment in future pandemic settings.

As communication technology advances and the digital divide grows, a deeper understanding of the influence of different information sources on vaccine uptake by generations can inform targeted public health interventions in times of future crisis. While the COVID-19 pandemic highlighted the role of media sources on the decision to receive vaccines, no studies have focused on the impact of the type and number of information sources in a population-based sample in California.

In this study, we examined associations between Californians' self-reported most relied upon COVID-19 information sources, categorized by type and measured as a count, and their COVID-19 vaccination status using data collected from the 2022 California Health Interview Survey. To address differences in information preferences and vaccine uptake by age, we also tested for potential effect modification of the relationship between relied upon COVID-19 information sources and vaccination status by generational membership (eg, Generation Z, millennials, Generation X, baby boomers, and Silent Generation).

We conducted a secondary analysis of cross-sectional data from the 2022 California Health Interview Survey. Vaccine status (any or none) was modeled as a function of information sources (or count) controlling for important sociodemographic and health confounding variables. Interaction terms of information sources (or count) by generational status were added to the models to test effect modification, and if significant, the models were stratified by generation. All analysis was survey-weighted to account for the complex survey sampling design.

Compared to relying on traditional news media for COVID-19 information, relying on word of mouth (odds ratio [OR] 0.6), social media (OR 0.62), and doctors (OR 0.41) for COVID-19 information was associated with lower odds of being vaccinated for COVID-19. A dose-response relationship was identified, with each additional information source associated with 9% higher odds of being vaccinated for COVID-19. In stratified models, social media, compared to traditional news media, was associated with lower odds of vaccination for Generation X, baby boomers, and the Silent Generation.

Health information preferences, especially for traditional news media, are associated with COVID-19 vaccine uptake, and the information sources differ by generation. These findings provide information for stakeholders interested in vaccine hesitancy, health informatics, messaging strategies, health literacy, and future health information outreach programs during epidemics or pandemics. Dissemination of public health information should include multiple information sources to reach all individual preferences across different generations.

The study explored the relationship between self-care practices and resilience in baccalaureate nursing faculty before, during, and after the COVID-19 pandemic.

There is limited research on self-care and resilience in nurse faculty, yet certain factors have been determined to negatively impact work-life balance.

A cross-sectional research survey collected quantitative data on demographics, self-care practices, and resilience. Surveys were sent to nurse faculty within a large statewide system (n = 312).

Before the pandemic, neither demographic characteristics nor self-care was significant predictors of resilience; during and after, however, there was a statistically significant relationship between self-care behaviors and resilience (p = .007, p = .018). Faculty reporting higher levels of self-care measured higher in resilience.

Encouraging self-care practices in nurse faculty can enhance resilience and potentially improve overall well-being. Further research on factors of influence would be of benefit.