Tuberculosis (TB) remains a major global health challenge, necessitating the development of advanced pulmonary drug delivery systems to improve therapeutic efficacy. Linezolid (LZD), a second-line oxazolidinone antibiotic, is effective against multidrug-resistant Mycobacterium tuberculosis but is associated with systemic adverse effects when administered orally for prolonged periods.

This study aimed to engineer and optimise LZD nanocrystals (LZD-NCs) in microparticles for dry powder inhalation (DPI) using a Quality by Design (QbD)-based Central Composite Design (CCD) approach to enhance localised pulmonary delivery.

LZD-NCs were initially prepared by high-pressure homogenization (HPH) and subsequently converted into respirable nanocrystals in microparticles (LZD-NIM) using spray drying. The LZD-NCs formulation was optimised using CCD. The developed formulation was evaluated for physicochemical characteristics, including solid-state characterisation, in vitro drug-release study, kinetic study, and aerosolisation behaviour and stability.

The optimised formulation exhibited an average particle size of 239.5 ± 16.30 nm, polydispersity index (PDI) of 0.285 ± 0.042, and surface charge of -34.5 ± 1.84 mV, indicating acceptable colloidal stability. Later, NIM effectively retained the physicochemical integrity of LZD-NCs. The developed NIM formulation exhibited improved drug release of 61.39% over 24 h, compared with pure LZD at 37.26%. An in vitro aerosolisation study demonstrated appropriateness for deep lung deposition of NIM with a mass median aerodynamic diameter (MMAD) of 2.9 ± 0.15 µm and high fine particle fractions (FPF) of 76.12 ± 1.3%.

The engineered LZD-NIM successfully yielded a highly stable, aerodynamically efficient DPI platform with sustained drug release kinetics. The engineered platform demonstrates its potential as an effective pulmonary drug-delivery system for TB treatment.

Chronic obstructive pulmonary disease (COPD) is frequently accompanied by depression and anxiety, which may exacerbate disease outcomes, reduce treatment adherence, and impair quality of life. Despite their clinical significance, these comorbidities remain frequently underdiagnosed and undertreated. This study examined the diagnosed prevalence of depression and anxiety, as well as the patterns of psychotropic medication use among patients with COPD in Lithuania.

A retrospective observational study was conducted using anonymized outpatient administrative data from the Lithuanian State Data Agency, comprising adult patients with COPD (ICD-10 J44.x) between 2020 and 2024. Mental health comorbidities were identified according to ICD-10 codes for anxiety disorders (F41.x), depressive episodes (F32.x), and recurrent depressive disorders (F33.x). Associations between categorical variables and sex differences were analyzed using contingency tables. Crude odds ratios (ORs) and adjusted odds ratios (aORs) from multivariable logistic regression analyses were calculated.

Among 64,246 unique patients with COPD, 18.1% had a diagnosed psychiatric disorder, with a higher diagnosed prevalence among women than men (26.8% vs 12.1%; aOR = 2.40, 95% CI 2.32-2.48, p < 0.001). Anxiety disorders were identified in 15.0% of patients, and depressive disorders in 4.6%; women had significantly higher odds of depressive disorders compared with men (aOR = 3.53, 95% CI 3.36-3.72, p < 0.001). Psychotropic medications were prescribed to 61.9% of affected individuals, with women being more likely to receive any psychotropic medication than men (aOR = 0.687 for men vs women, 95% CI 0.644-0.732, p < 0.001). Anxiolytics represented 89.9% of all psychotropic prescriptions, with benzodiazepines accounting for 85.0% of this category. Family physicians were significantly more likely to prescribe anxiolytics than psychiatrists (OR = 10.66, p < 0.001). Antidepressant and neuroleptic prescribing showed statistically significant increasing trends over the study period (p = 0.007 and p = 0.005, respectively), whereas benzodiazepine prescribing rates also increased significantly (p = 0.004).

Anxiety and depression are common psychiatric comorbidities among patients with COPD in Lithuania and exhibit notable gender differences. Psychotropic medications were predominantly prescribed in primary care, with benzodiazepines accounting for the majority of anxiolytic treatments. These findings provide updated nationwide data on psychiatric comorbidity and psychotropic prescribing patterns among patients with COPD in Lithuania.

Co-morbid insomnia and sleep apnoea (COMISA) is a highly prevalent condition associated with worse health outcomes and greater treatment complexity than either disorder alone. Patients with COMISA demonstrate lower acceptance and use of continuous positive airway pressure (CPAP) therapy compared with those who have obstructive sleep apnoea (OSA) alone, yet the subjective mechanisms underlying this adherence penalty remain poorly understood. Qualitative research on CPAP use and sleep behaviour change in patients with COMISA is scarce, the COM-B (Capability, Opportunity, Motivation-Behaviour) model has rarely been applied to this population, and the influence of non-Western cultural norms on COMISA treatment engagement has received little attention.

A descriptive qualitative study guided by the COM-B model and Theoretical Domains Framework (TDF) was conducted at a tertiary sleep medicine centre in Hunan Province, China. Sixteen hospitalised patients with polysomnography-confirmed moderate-to-severe OSA (AHI ≥ 15) and clinically significant insomnia (ISI ≥ 15) were purposively sampled using a 2 × 2 maximum variation matrix based on inpatient CPAP adherence (good vs. poor) and receipt of a brief nurse-led inpatient CBT-I programme (with vs. without structured CBT-I). Individual semi-structured interviews were analysed using directed content analysis, with reporting following the COREQ checklist.

The analysis generated 1,160 reference points across 20 coding nodes, synthesised into three themes and nine sub-themes aligned with the COM-B dimensions. Motivation accounted for the largest share of coded data (589 reference points) and revealed a pattern of "insomnia dominance" in which participants systematically prioritised insomnia over OSA, four patterns of fixed causal attribution that led patients to rule out particular treatments, and an emotion-identity complex linking stigma, age-related identity, and treatment rejection. Within the Opportunity dimension, an "adherence illusion" was identified: some inpatients with good CPAP adherence had not internalised motivation for post-discharge self-management. Culturally specific barriers extended beyond rural CPAP-related death stigma to include urban obligatory banquet drinking norms.

Hospitalised COMISA patients face qualitatively different behavioural barriers from those with OSA alone, requiring COM-B-guided individualised assessment rather than uniform adherence interventions. Nursing practice should incorporate pre-discharge environmental screening, proactive CPAP experience management during the first two to three nights, and culturally sensitive approaches spanning both rural and urban social norms. The Behaviour Change Wheel provides a systematic pathway for translating these behavioural diagnoses into targeted, nurse-led intervention design.

The correct use of inhalation devices is essential for achieving adequate control of asthma and COPD; however, critical errors in inhalation technique are frequent and substantially reduce treatment effectiveness. This study's objective was to evaluate the prevalence of inadequate inhalation technique among patients with asthma and COPD and to identify the most common critical errors and the factors associated with incorrect use.

This cross-sectional observational study included 575 patients (aged ≥ 18 years) with asthma and/or COPD, recruited from a university hospital outpatient pulmonology clinic and a public specialized pharmacy (Natal, Brazil). Participants completed sociodemographic questionnaires and demonstrated their inhaler technique, which was assessed using device-specific checklists to identify critical errors. Factors associated with critical errors were analyzed using multivariable logistic regression.

Only 8.2% of participants correctly performed all steps of the inhalation technique. At least one critical error was observed in 73.4% of the cohort. In multivariable analysis, advanced age (OR: 1.029; 95% CI: 1.016-1.044), use of multiple devices (OR: 2.500; 95% CI: 1.754-3.562), and type of mechanism independent of inspiration (OR: 0.262; 95% CI: 0.160-0.430; protective factor) were significantly associated with critical errors (p < 0.001).

Inadequate inhalation technique, particularly the occurrence of critical errors, was highly prevalent, especially among older patients and those using multiple devices. Inhalers dependent on inspiratory effort demonstrated greater vulnerability to incorrect use.

The COVID-19 pandemic profoundly disrupted public health, social systems, and the workforce. This longitudinal study examines changes in depressive and anxiety symptoms before and during the pandemic in middle-aged and older adults (N = 6,813) from the Gutenberg Health and Gutenberg COVID-19 Study in Germany. Using repeated assessments with validated mental health scales (PHQ-9, GAD-2) and accounting for pre-pandemic mental health, we investigated associations with work-related factors (e.g., changes in working hours, remote work, income) and sociodemographic variables (e.g., sex, age, household composition). Average depression and anxiety scores remained relatively stable over time, although the proportion exceeding the clinical PHQ-9 ≥ 10 threshold increased during the pandemic. Pre-pandemic mental health emerged as the strongest predictor of pandemic mental health outcomes. Vocational factors showed only small effect sizes, with increased weekly working hours emerging as the most consistent work-related correlate of distress. Important sociodemographic predictors included female sex, middle age, and living alone. The findings emphasize considering pre-existing mental health and pandemic-related sociodemographic and vocational circumstances when identifying vulnerable groups. Although workplace factors played only a limited role overall, the workplace may nevertheless represent a relevant setting for mental health promotion during future public health crises.

The COVID-19 pandemic has induced substantial changes in environment, lifestyle, and health behaviors. We observed temporal associations between the pandemic period and declining sIgE positivity rates; however, causality cannot be established due to the retrospective observational design. Distinguishing between asymptomatic sensitization (positive specific IgE without clinical symptoms) and true allergic disease remains critical. This study aims to describe the trends in allergen-specific IgE (sIgE) positivity-as a marker of sensitization-in the Xiamen population from 2019 to 2023, a surrogate marker of sensitization that does not equate to clinical allergy, providing insights into population-level immunological changes during the pandemic.

We performed a retrospective cross-sectional analysis of 3,207 serum sIgE testing records (3,210 initial records minus 3 exclusions) from patients who underwent allergen screening at our hospital between January 2019 and December 2023. These records include repeated tests from some individuals; a subset of 2,784 records from 2,750 unique patients was used for GEE modeling to account for within-individual correlation. Data on sensitization to inhalant allergens (e.g., dust mites, cat dander, cockroach) and food allergens (e.g., egg white, crab, milk) were analyzed. Age and sex distributions were examined, though detailed information on clinical symptoms (e.g., eczema, rhinitis), comorbidities, and longitudinal follow-up of individual patients was not available.

Among 3,207 testing records, 1,454 (45.34%) were positive for sIgE to one or more allergens. The annual positivity rate declined sharply from 76.07% (89/117) in 2019 to 32.26% (519/1,609) in 2023 (p < 0.001). Dust mites were the most prevalent inhalant allergens, with about a third of all testing records showing sensitivity (35.30%, 1,035/3,207), followed by cockroach and cat hair. For food allergens, egg white, crab, and milk ranked highest. Males showed higher positivity rates for both inhalant and food allergens compared to females, and the difference was statistically significant (p < 0.01). Most allergens showed age-related differences, with the exception of cat hair, dog epithelium, crb and ragweed; cockroach showed statistically significant differences across age groups (χ ² = 32.89, p < 0.001). We observed temporal associations between the pandemic period and declining sIgE positivity rates; however, these findings should be interpreted with caution due to the observational study design and potential selection bias.

This study documents a significant decline in sIgE positivity rates for both inhalant and food allergens in Xiamen from 2019 to 2023. To our knowledge, this is the first report from Xiamen spanning the full COVID-19 pandemic period, providing foundational data for future hypothesis-driven research. Sex- and age-specific differences in sensitization patterns were observed. However, based on the current dataset alone, it is not possible to determine whether these changes reflect true shifts in clinical allergic disease or result from alterations in testing practices, population composition, or other confounders. Future research must integrate detailed clinical phenotyping (including age-stratified symptom data, comorbidities such as eczema, and longitudinal follow-up) and lifestyle/environmental measurements to identify modifiable factors for preventing allergy development-not merely managing sensitization.

Escherichia fergusonii is an emerging food-borne opportunistic pathogen that disrupts gut homeostasis and exacerbates the severity of other organ diseases. However, the effects of gut colonization by E. fergusonii on the gut-lung axis remain unclear. Here we show that the abundance of Escherichia increases in microbiota-depleted mice and is enriches in patients with K. pneumoniae-associated pneumonia. Both alterations show a statistically significant correlation with the severity of lung infection. In the murine model, gut colonization by E. fergusonii induces specific gut dysbiosis, decreases intestinal and pulmonary acetate levels, and exacerbates carbapenem-resistant K. pneumoniae-induced pneumonia. Notably, fecal microbiota transplantation and acetate administration restore immune responses, ameliorate gut dysbiosis, increase acetate concentrations in intestinal and pulmonary tissues, and improve disease outcomes in mice with pneumonia. This study demonstrates that E. fergusonii-induced gut dysbiosis modifies the gut-lung immune axis in resistant K. pneumoniae-induced pneumonia and proposes a potential intervention strategy involving microbiota-derived acetate.

Managing heart failure often involves polypharmacy, reflecting the challenge of balancing multiple treatments to achieve the best outcomes for patients. We aimed to investigate the effect of polypharmacy on survival in ambulatory patients with heart failure and identify key predictors of survival.

We conducted a secondary analysis of data from 1375 ambulatory patients with heart failure managed at a heart failure clinic in Spain between 2006 and 2016. Patients were stratified into low polypharmacy (< 5 cardiovascular medications) and high polypharmacy groups (≥ 5 cardiovascular medications). Survival was evaluated using Kaplan-Meier curves, log-rank tests, and a multivariable random forest Cox regression model adjusting for demographic and clinical confounders using propensity scores.

There was a significant relationship between the number of medications used and survival (log-rank test, P = 0.017) with the most pronounced risk observed in those with seven or more medications. Additionally, patients in the high polypharmacy group showed significantly reduced survival probabilities than those in the low polypharmacy group (P = 0.016). The top important predictors of survival were age, N-terminal pro B-type natriuretic peptide, New York Heart Association functional class, heart failure duration, sacubitril-valsartan, β-blockers, and angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (all P < 0.001). Multivariable analysis (C-index = 0.804) showed that high polypharmacy was independently associated with reduced survival (P < 0.001).

High polypharmacy is associated with reduced long-term survival in patients with heart failure. This highlights the need for personalized prescribing strategies to minimize the risks associated with polypharmacy while maximizing therapeutic benefits.

Post-traumatic stress disorder (PTSD), a trauma- and stressor-triggered psychiatric condition affecting approximately 10 million Americans, is a major risk factor for atherosclerosis and its devastating sequelae including ischemic heart disease, stroke and hypertension. PTSD and atherosclerosis share many pathogenic mechanisms impacting the limbic system, prefrontal cortex and systemic vasculature, including hyperactivation of the sympathetic and renin-angiotensin systems, inflammation, dysregulated coagulation and altered cortisol secretion. Whether PTSD is a direct cause of atherosclerosis, or an independent co-phenomenon, is an unresolved but pivotal question.

Recent evidence supports both sequential cause-and-effect, where PTSD-instigated mechanisms provoke and/or perpetuate atherosclerosis, and parallel development of both phenomena from shared trauma-activated mechanisms. Mounting evidence also supports a bidirectional interaction, wherein the cardiovascular consequences of atherosclerosis elicit chronic psychiatric stress and, potentially, a maladaptive feedforward PTSD - atherosclerosis cycle. The specific pathobiological context may determine the prevailing relationship. Recent research has revealed multifaceted interactions among the neuroendocrine cascades mediating PTSD and atherosclerosis, and demonstrated complex associations between the two disorders. Knowledge of the PTSD - atherosclerosis relationship in the individual patient will inform efforts to optimize treatment of these complicated conditions.

Less than half of people with hypertension in Ethiopia are diagnosed, and only one-third of adults visiting primary care facilities have their blood pressure (BP) screened. We implemented a quality improvement (QI) initiative across six facilities in Ethiopia to increase facility-based BP screening. Process mapping identified barriers, and interventions were tested in iterative QI cycles: establishing BP screening desks at key service points, ensuring the availability of validated BP devices, training staff in accurate measurement, standardizing documentation, and reviewing screening indicators in performance meetings. Between April 2024 and February 2025, monthly BP screening of adults without a hypertension diagnosis increased from 41.0% of 13,707 eligible adults to 79.6% of 14,270 eligible adults. Monthly hypertension program enrollments rose from 40 in April 2024 to 125 in February 2025. Strengthening primary health care systems to systematically measure BP for all adults visiting health facilities can significantly improve hypertension detection and treatment.