Association of Tumor Necrosis Factor-α Inhibitors with Incident Dementia: Analysis Based on Population-Based Cohort Studies.

BACKGROUND AND OBJECTIVE: Preliminary evidence suggests a possible preventive effect of tumor necrosis factor-α inhibitors (TNFi) on incident dementia. The objective of the analysis was to investigate the association between TNFi and the risk of incident dementia in a population undergoing treatment for rheumatological disorders. METHODS: We followed patients aged ≥ 65 years with dementia and rheumatological conditions in two cohort studies, DANBIO (N = 21,538), a Danish clinical database, and AOK PLUS (N = 7112), a German health insurance database. We defined incident dementia using diagnostic codes and/or medication use and used Cox regression to compare the associations of TNFi with other rheumatological therapies on the risk of dementia. To ensure that the patients were receiving long-term medication, we included patients with rheumatic diseases and systemic therapies. RESULTS: We observed similar trends towards a lower risk of dementia associated with TNFi versus other anti-inflammatory agents in both cohorts (hazard ratios were 0.92 [95% confidence interval 0.76, 1.10] in DANBIO and 0.89 [95% confidence interval 0.63, 1.24] in AOK PLUS, respectively). CONCLUSIONS: Tumor necrosis factor-α inhibitors may decrease the risk of incident dementia although the association did not reach statistical significance in this analysis. Further research, ideally with randomization, is needed to gauge the potential of repurposing TNFi for dementia prevention and/or treatment.

Scan-Associated Distress in People Affected by Cancer: A Qualitative Systematic Review.

OBJECTIVE: The term "scanxiety" has been coined to describe the anxiety commonly associated with individuals undergoing cancer-related imaging. Despite the prevalence and severity of scanxiety across various clinical and demographic populations, there remains a significant lack of qualitative insights from existing studies that effectively capture patients' experiences of scanxiety in their own words. Therefore, this review addresses the following research question: What are the experiences of scanxiety distress among people affected by cancer across the cancer care continuum? DATA SOURCES: Following the PRISMA methodology, a meta-aggregation of qualitative studies was performed, encompassing patients of all age groups who had been diagnosed with cancer or were indicated for a cancer-related scan. Of the 556 articles screened, 15 were deemed eligible for inclusion in the analysis. CONCLUSION: The three overarching themes of 1) experience of "scan-itis," 2) experience of "patient-clinician support," and 3) development of self-management strategies reveal the complex and interconnected factors that influence scanxiety in individuals undergoing cancer-related imaging. These findings emphasized distress experienced by patients during the waiting period for scan results, the act of viewing the results, and even the delivery of "bad" news. Consequently, patients expressed a strong desire for increased information, communication, and empathy from attending healthcare providers. Patients also report a myriad of self-coping strategies to manage their scanxiety well before, during, and after their scan appointment. IMPLICATIONS FOR NURSING PRACTICE: The study highlights the need for targeted interventions for those undergoing cancer-related scans, including increased awareness and education for health professionals regarding scanxiety.

Effect of wearing an N95 respirator on the internal nasal valve and the association with external nasal anatomy - a cohort study.

OBJECTIVES: To determine whether: the N95 respirator affects nasal valve patency; placement on the bony vault improves patency; and external nasal anatomy affects the outcome. METHODS: A prospective study with 50 participants was conducted. Nasal patency was measured by the minimal cross-sectional area via acoustic rhinometry, and using the Nasal Obstruction Symptom Evaluation survey, before and after wearing the N95 respirator and after adjustment. RESULTS: The minimal cross-sectional area was narrowed by 27 per cent when wearing the N95 respirator (p < 0.001), and improved by 9.2 per cent after adjustment (p = 0.003). The total Nasal Obstruction Symptom Evaluation score increased from 10.2 to 25.4 after donning the N95 respirator (p < 0.001), and decreased from 25.4 to 15.6 after adjustment (p < 0.001). There was no correlation with external nasal anatomy parameters. CONCLUSION: Wearing the N95 respirator causes narrowing of the nasal valve, and adjustment onto the bony vault improves symptoms. The findings were not affected by external nasal anatomy.

Personalized prediction of transcranial magnetic stimulation clinical response in patients with treatment-refractory depression using neuroimaging biomarkers and machine learning.

BACKGROUND: Functional connectivity between the left dorsolateral prefrontal cortex (DLPFC) and subgenual cingulate (sgACC) may serve as a biomarker for transcranial magnetic stimulation (rTMS) treatment response. The first aim was to establish whether this finding is veridical or artifactually induced by the pre-processing method. Furthermore, alternative biomarkers were identified and the clinical utility for personalized medicine was examined. METHODS: Resting-state fMRI data were collected in medication-refractory depressed patients (n = 70, 16 males) before undergoing neuronavigated left DLPFC rTMS. Seed-based analyses were performed with and without global signal regression pre-processing to identify biomarkers of short-term and long-term treatment response. Receiver Operating Characteristic curve and supervised machine learning analyses were applied to assess the clinical utility of these biomarkers for the classification of categorical rTMS response. RESULTS: Regardless of the pre-processing method, DLPFC-sgACC connectivity was not associated with treatment outcome. Instead, poorer connectivity between the sgACC and three clusters (peak locations: frontal pole, superior parietal lobule, occipital cortex) and DLPFC-central opercular cortex were observed in long-term nonresponders. The identified connections could serve as acceptable to excellent markers. Combining the features using supervised machine learning reached accuracy rates of 95.35% (CI=82.94-100.00) and 88.89% (CI=63.96-100.00) in the cross-validation and test dataset, respectively. LIMITATIONS: The sample size was moderate, and features for machine learning were based on group differences. CONCLUSIONS: Long-term nonresponders showed greater disrupted connectivity in regions involving the central executive network. Our findings may aid the development of personalized medicine for medication-refractory depression.

Polytobacco product use among current cigarette smokers in Hong Kong, China: results from population surveys (2015-17).

BACKGROUND: Polytobacco product use is increasingly popular, but little is known about the prevalence, trend, and factors of such use particularly in non-western countries. METHOD: A representative sample of 1139 current cigarette smokers aged 15+ (84.1% male) were telephone interviewed in Tobacco Control Policy-related Surveys in 2015-2017. Information collected included poly-tobacco use (PTU), smoking and socio-demographic characteristics. Associations of current PTU with related factors were analyzed using logistic regression with adjustment for confounders. Prevalence was weighted by age and sex of current cigarette users in the general population. RESULTS: Eighty-four point one percent (95% CI 81.4-86.6%) were exclusive cigarette smokers. Fifteen point nine percent (13.4-18.6%) were current polytobacco product users, 12.3% (10.2-14.8%) used one tobacco product and 2.52% (1.59-3.97%) used two tobacco products in addition to cigarette. Cigarette use with cigar was more common (6.28%, 4.75-8.27%), and the least used product with cigarette was e-cigarette (1.05%, 0.44-2.50%). The changes in overall prevalence of PTU by number of products use varied in 3 years. Current PTU was associated with being male (AOR 2.01, 95% CI 1.12-3.61), younger age (AORs range from 1.34-4.65, P for trend < .001) and less ready to quit (2.08, 1.09-3.97). CONCLUSIONS: Prevalence of PTU increased slowly by year, one tobacco product use with cigarette was more common. The most used tobacco product with cigarette was cigar. Being male, younger and less ready to quit were associated with current PTU.

Attentional Bias Modification Training for Patients with Generalised Anxiety Disorder: a Randomised Controlled Study.

BACKGROUND: Hypervigilance to threat is a mechanism contributing to generalised anxiety disorder (GAD). Although attentional bias modification training (ABMT) is designed to reduce attention to threat, its use as a mechanistically focused psychological intervention for GAD has not been examined. We aimed to investigate the effect of a brief ABMT on reducing anxiety, worry, and attentional bias in outpatients with GAD, and to determine the association between change in attentional bias and changes in anxiety and worry. METHODS: This was a parallel-group, double-blind, randomised controlled trial. Patients with GAD who had no changes after medication treatment for the past 8 weeks were randomly allocated to either the treatment or control group to receive 4 weekly sessions of ABMT or sham ABMT, respectively, in addition to standard care. Anxiety was measured using the Hamilton Anxiety Rating Scale and the State-Trait Anxiety Inventory - trait anxiety subscale. Pathological worry was measured using the Penn State Worry Questionnaire. Attentional bias was measured using the bias score. RESULTS: A total of 33 participants were allocated to the treatment (n = 17) or control (n = 16) groups. Both groups reported a significant reduction in levels of anxiety and worry after intervention, but the reduction was not greater after ABMT than sham ABMT. There was no significant change in attentional bias after ABMT; change in attentional bias was not correlated to changes in anxiety and worry. CONCLUSION: The efficacy of the brief ABMT as a mechanistically focused treatment for GAD was not supported. The small sample size and short duration of treatment may have rendered the results inconclusive.

Associations between acute gastrointestinal GvHD and the baseline gut microbiota of allogeneic hematopoietic stem cell transplant recipients and donors.

Growing evidence suggests that host-microbiota interactions influence GvHD risk following allogeneic hematopoietic stem cell transplant. However, little is known about the influence of the transplant recipient's pre-conditioning microbiota nor the influence of the transplant donor's microbiota. Our study examines associations between acute gastrointestinal GvHD (agGvHD) and 16S rRNA fecal bacterial profiles in a prospective cohort of N=57 recipients before preparative conditioning, as well as N=22 of their paired HLA-matched sibling donors. On average, recipients had lower fecal bacterial diversity (P=0.0002) and different phylogenetic membership (UniFrac P=0.001) than the healthy transplant donors. Recipients with lower phylogenetic diversity had higher overall mortality rates (hazard ratio=0.37, P=0.008), but no statistically significant difference in agGvHD risk. In contrast, high bacterial donor diversity was associated with decreased agGvHD risk (odds ratio=0.12, P=0.038). Further investigation is warranted as to whether selection of hematopoietic stem cell transplant donors with high gut microbiota diversity and/or other specific compositional attributes may reduce agGvHD incidence, and by what mechanisms.

[Clinical medication reviews in elderly patients with polypharmacy: a cross-sectional study in Dutch community pharmacies]. / Medicatiebeoordelingen bij ouderen met polyfarmacie.

OBJECTIVE: To investigate the nature and prevalence of drug related problems (DRPs) in older patients with polypharmacy identified by community pharmacists in daily practice through means of a clinical medication review (CMR) and assess the implementation rate of proposed interventions to solve DRPs. DESIGN: A cross-sectional study METHOD: We analysed the CMR data of 3,807 older patients (≥ 65 years) with polypharmacy (≥ 5 drugs) completed in January-August 2012. Using the "Service Apotheek Medicatie Review Tool" (SAMRT, Service Pharmacy Medication Review Tool), pharmacists in 258 community pharmacies registered the patients' year of birth, gender, dispensing data, DRPs, and proposed and implemented interventions. RESULTS: Pharmacists identified a median of two DRPs (interquartile range 1-4; mean 3.0) per patient. The DRP categories overtreatment (25.5 %) and undertreatment (15.9 %) were found to occur most frequently. On average, 46.2 % of the proposed interventions to address DRPs were implemented as proposed. In 22.4 % of cases the intervention differed from the proposal, whereas in 31.3 % of cases no intervention was implemented. CONCLUSION: In daily practice, community pharmacists identified a mean of three DRPs in older patients with polypharmacy, a number comparable to that found in controlled studies. Over- or undertreatment caused nearly half of the identified DRPs. The majority (69.9%) of the proposed interventions led to an intervention for the patient.

Three cases of atypical pneumonia caused by Chlamydophila psittaci.

Psittacosis is a zoonotic disease caused by Chlamydophila psittaci. The most common presentation is atypical pneumonia. Three cases of pneumonia of varying severity due to psittacosis are described. All patients had a history of avian contact. The diagnosis was confirmed by molecular detection of Chlamydophila psittaci in respiratory specimens. The cases showed good recovery with doxycycline treatment. Increased awareness of psittacosis can shorten diagnostic delay and improve patient outcomes.

A one-year prospective study of infectious etiology in patients hospitalized with acute exacerbations of COPD and concomitant pneumonia.

AIM: This study assessed the infectious etiology of patients hospitalized for acute exacerbations of chronic obstructive pulmonary disease (AECOPD) with concomitant pneumonia. METHODS: Patients admitted to medical wards in an acute hospital were recruited prospectively from May 1, 2004 to April 30, 2005. Sputum culture, blood culture, paired serology, and nasopharyngeal aspirates (NPA) viral culture and polymerase chain reaction (PCR) studies were performed. Spirometry was assessed in stable phase at 2-3 months post-hospital discharge. RESULTS: Seventy eight subjects were admitted for AECOPD with concomitant pneumonia. The mean (SD) age was 77.1 (7.5) years, with FEV(1) of 41.5 (20.8)% predicted normal. Overall, an infectious etiology could be established in 48.7% of the subjects. Among the 71 subjects with sputum collected, 40.8% had positive bacterial culture. The commonest bacteria identified were Streptococcus pneumoniae (8[11.3%]), Pseudomonas aeruginosa (7[9.9%]) and Haemophilus influenzae (7[9.9%]). Among the 66 subjects with NPA collected, 9.0 and 12.2% had positive viral culture and PCR results, respectively. The commonest viruses identified by NPA PCR were influenza A (4[6.1%] subjects) and rhinovirus (2[3.0%]). Paired serology was positive in 4.4%. Patients on high dose inhaled corticosteroid (ICS) (>1000 mcg beclomethasone-equivalent/day) had a higher rate of positive sputum bacterial culture than those on low-medium dose of ICS (50.0% vs 18.2%, p=0.02). CONCLUSION: An infectious etiology could be established in about half of patients hospitalized with AECOPD and concomitant pneumonia. The majority of identifiable causes were bacterial. Patients on high dose ICS might have impaired airway defense as reflected by the higher rate of positive sputum culture.

Spinal subdural haematoma: a rare complication of low-molecular-weight heparin therapy.

A 52-year-old man presented with chest pain, diarrhoea, rash, and arthritis. The use of low-molecular-weight heparin for suspected pulmonary embolism or angina led to a spinal subdural haematoma 3 days later. He was retrospectively confirmed to have Salmonella paratyphi infection. The clinical presentation and management of spinal subdural haematomas, and the incidence and manifestations of reactive arthritis related to Salmonella infections are briefly discussed.

Features discriminating SARS from other severe viral respiratory tract infections.

This study investigated the discriminatory features of severe acute respiratory syndrome (SARS) and severe non-SARS community-acquired viral respiratory infection (requiring hospitalization) in an emergency department in Hong Kong. In a case-control study, clinical, laboratory and radiological data from 322 patients with laboratory-confirmed SARS from the 2003 SARS outbreak were compared with the data of 253 non-SARS adult patients with confirmed viral respiratory tract infection from 2004 in order to identify discriminatory features. Among the non-SARS patients, 235 (93%) were diagnosed as having influenza infections (primarily H3N2 subtype) and 77 (30%) had radiological evidence of pneumonia. In the early phase of the illness and after adjusting for baseline characteristics, SARS patients were less likely to have lower respiratory symptoms (e.g. sputum production, shortness of breath, chest pain) and more likely to have myalgia (p < 0.001). SARS patients had lower mean leukocyte and neutrophil counts (p < 0.0001) and more commonly had "ground-glass" radiological changes with no pleural effusion. Despite having a younger average age, SARS patients had a more aggressive respiratory course requiring admission to the ICU and a higher mortality rate. The area under the receiver operator characteristic curve for predicting SARS when all variables were considered was 0.983. Using a cutoff score of >99, the sensitivity was 89.1% (95%CI 82.0-94.0) and the specificity was 98.0% (95%CI 95.4-99.3). The area under the receiver operator characteristic curve for predicting SARS when all variables except radiological change were considered was 0.933. Using a cutoff score of >8, the sensitivity was 80.7% (95%CI 72.4-87.3) and the specificity was 94.5% (95%CI 90.9-96.9). Certain clinical manifestations and laboratory changes may help to distinguish SARS from other influenza-like illnesses. Scoring systems may help identify patients who should receive more specific tests for influenza or SARS.

Cryptococcosis in apparently immunocompetent patients.

BACKGROUND: Few reports have described the clinical and microbiological features of cryptococcosis in immunocompetent patients. AIM: To compare clinical presentations and outcomes of cryptococcosis in immunocompetent vs. immunocompromised patients. DESIGN: Retrospective case series. METHODS: All culture- or histology-confirmed cases (n = 46) of cryptococcosis in two acute hospitals in Hong Kong (1995-2005) were included. Clinical presentations, rates of fungaemia, cerebrospinal fluid (CSF) parameters and clinical outcomes were recorded. RESULTS: Twenty patients (43.5%) were apparently immunocompetent, 17 (37.0%) had predisposing factors other than HIV infection, and 9 (19.6%) were HIV-positive. Thirty-one (67.4%) presented with meningitis, four (8.7%) with pulmonary cryptococcosis, and 11 (23.9%) with extraneural, extrapulmonary cryptococcosis. Of the immunocompetent patients with retrievable isolates (n = 8), three (37.5%) were Cryptococcus gattii; all isolates (n = 6) from immunocompromised patients were Cryptococcus neoformans var. grubii. Immunocompetent patients more commonly presented with meningitis (80.0% vs. 47.1%, p = 0.03), and tended toward lower rates of fungaemia (10.0% vs. 35.3%, p = 0.06) and mortality (25.0% vs. 52.9%, p = 0.06). Death was associated with fungaemia (p = 0.01) and underlying malignancy (p < 0.01). In cryptococcal meningitis, immunocompetent patients had longer mean time from illness onset to presentation (34.4 vs. 12.6 days, p = 0.02), more intense inflammatory responses (CSF: white blood cells 108 vs. 35 x 10(9)/l, p = 0.03; protein 1.61 g/l vs. 0.79 g/l, p = 0.07), less fungaemia (0% vs. 26.7%, p = 0.04) and more satisfactory clinical outcomes (81.3% vs. 46.7%, p = 0.04). DISCUSSION: A substantial proportion of patients with cryptococcosis are apparently immunocompetent. C. neoformans var. grubii and C. gattii are the common causes. Immunocompetent patients tend to present with localized, indolent neurological disease, with more intense inflammatory responses but better clinical outcomes.

The fluid property dependency on micro-fluidic characteristics in the deposition process for microfabrication.

The droplet impingement into a cavity at micrometer-scale is one of important fluidic issues for microfabrications, e.g. the inkjet deposition process in the PLED display manufacturing. The related micro-fluidic behaviors in the deposition process should be carefully treated to ensure the desired quality of microfabrication. The droplets generally dispensing from an inkjet head, which contains an array of nozzles, have a volume in several picoliters, while each nozzle responds very quickly and jets the droplets into cavities on substrates with micrometer size. The nature of droplet impingement depends on the fluid properties, the initial state of droplet, the impact parameters and the surface characteristics. The commonly chosen non-dimensional numbers to describe this process are the Weber number, the Reynolds number, the Ohnesorge number, and the Bond number. This paper discusses the influences of fluid properties of a Newtonian fluid, such as surface tension and fluid viscosity, on micro-fluidic characteristics for a certain jetting speed in the deposition process via a numerical approach, which indicates the impingement process consists of four different phases. In the first phase, the droplet stretching outwards rapidly, where inertia force is dominated. In the second phase, the recoiling of droplet is observed, where surface tension becomes the most important force. In the third phase, the gravitational force pulls the droplet surface towards cavity walls. The fourth phase begins when the droplet surface touches cavity walls and ends when the droplet obtains a stable shape. If the fluid viscosity is relatively small, the droplet surface touches cavity walls in the second phase. A stable fluid layer would not form if the viscosity is relatively small.

Twisted gastrulation can function as a BMP antagonist.

Bone morphogenetic proteins (BMPs), including the fly homologue Decapentaplegic (DPP), are important regulators of early vertebrate and invertebrate dorsal-ventral development. An evolutionarily conserved BMP regulatory mechanism operates from fly to fish, frog and mouse to control the dorsal-ventral axis determination. Several secreted factors, including the BMP antagonist chordin/Short gastrulation (SOG), modulate the activity of BMPs. In Drosophila, Twisted gastrulation (TSG) is also involved in dorsal-ventral patterning, yet the mechanism of its function is unclear. Here we report the characterization of the vertebrate Tsg homologues. We show that Tsg can block BMP function in Xenopus embryonic explants and inhibits several ventral markers in whole-frog embryos. Tsg binds directly to BMPs and forms a ternary complex with chordin and BMPs. Coexpression of Tsg with chordin leads to a more efficient inhibition of the BMP activity in ectodermal explants. Unlike other known BMP antagonists, however, Tsg also reduces several anterior markers at late developmental stages. Our data suggest that Tsg can function as a BMP inhibitor in Xenopus; furthermore, Tsg may have additional functions during frog embryogenesis.