Prehospital Tranexamic Acid for Severe Trauma.

BACKGROUND: Whether prehospital administration of tranexamic acid increases the likelihood of survival with a favorable functional outcome among patients with major trauma and suspected trauma-induced coagulopathy who are being treated in advanced trauma systems is uncertain. METHODS: We randomly assigned adults with major trauma who were at risk for trauma-induced coagulopathy to receive tranexamic acid (administered intravenously as a bolus dose of 1 g before hospital admission, followed by a 1-g infusion over a period of 8 hours after arrival at the hospital) or matched placebo. The primary outcome was survival with a favorable functional outcome at 6 months after injury, as assessed with the use of the Glasgow Outcome Scale-Extended (GOS-E). Levels on the GOS-E range from 1 (death) to 8 ("upper good recovery" [no injury-related problems]). We defined survival with a favorable functional outcome as a GOS-E level of 5 ("lower moderate disability") or higher. Secondary outcomes included death from any cause within 28 days and within 6 months after injury. RESULTS: A total of 1310 patients were recruited by 15 emergency medical services in Australia, New Zealand, and Germany. Of these patients, 661 were assigned to receive tranexamic acid, and 646 were assigned to receive placebo; the trial-group assignment was unknown for 3 patients. Survival with a favorable functional outcome at 6 months occurred in 307 of 572 patients (53.7%) in the tranexamic acid group and in 299 of 559 (53.5%) in the placebo group (risk ratio, 1.00; 95% confidence interval [CI], 0.90 to 1.12; P = 0.95). At 28 days after injury, 113 of 653 patients (17.3%) in the tranexamic acid group and 139 of 637 (21.8%) in the placebo group had died (risk ratio, 0.79; 95% CI, 0.63 to 0.99). By 6 months, 123 of 648 patients (19.0%) in the tranexamic acid group and 144 of 629 (22.9%) in the placebo group had died (risk ratio, 0.83; 95% CI, 0.67 to 1.03). The number of serious adverse events, including vascular occlusive events, did not differ meaningfully between the groups. CONCLUSIONS: Among adults with major trauma and suspected trauma-induced coagulopathy who were being treated in advanced trauma systems, prehospital administration of tranexamic acid followed by an infusion over 8 hours did not result in a greater number of patients surviving with a favorable functional outcome at 6 months than placebo. (Funded by the Australian National Health and Medical Research Council and others; PATCH-Trauma ClinicalTrials.gov number, NCT02187120.).

Dexamethasone and Surgical-Site Infection.

BACKGROUND: The glucocorticoid dexamethasone prevents nausea and vomiting after surgery, but there is concern that it may increase the risk of surgical-site infection. METHODS: In this pragmatic, international, noninferiority trial, we randomly assigned 8880 adult patients who were undergoing nonurgent, noncardiac surgery of at least 2 hours' duration, with a skin incision length longer than 5 cm and a postoperative overnight hospital stay, to receive 8 mg of intravenous dexamethasone or matching placebo while under anesthesia. Randomization was stratified according to diabetes status and trial center. The primary outcome was surgical-site infection within 30 days after surgery. The prespecified noninferiority margin was 2.0 percentage points. RESULTS: A total of 8725 participants were included in the modified intention-to-treat population (4372 in the dexamethasone group and 4353 in the placebo group), of whom 13.2% (576 in the dexamethasone group and 572 in the placebo group) had diabetes mellitus. Of the 8678 patients included in the primary analysis, surgical-site infection occurred in 8.1% (354 of 4350 patients) assigned to dexamethasone and in 9.1% (394 of 4328) assigned to placebo (risk difference adjusted for diabetes status, -0.9 percentage points; 95.6% confidence interval [CI], -2.1 to 0.3; P<0.001 for noninferiority). The results for superficial, deep, and organ-space surgical-site infections and in patients with diabetes were similar to those of the primary analysis. Postoperative nausea and vomiting in the first 24 hours after surgery occurred in 42.2% of patients in the dexamethasone group and in 53.9% in the placebo group (risk ratio, 0.78; 95% CI, 0.75 to 0.82). Hyperglycemic events in patients without diabetes occurred in 22 of 3787 (0.6%) in the dexamethasone group and in 6 of 3776 (0.2%) in the placebo group. CONCLUSIONS: Dexamethasone was noninferior to placebo with respect to the incidence of surgical-site infection within 30 days after nonurgent, noncardiac surgery. (Funded by the Australian National Health and Medical Research Council and others; PADDI Australian New Zealand Clinical Trials Registry number, ACTRN12614001226695.).

Assessment of weight gain in adult patients living with HIV receiving first-line dolutegravir-based or efavirenz-based ART regimens in routine care clinics in Tshwane district, South Africa: An observational study.

INTRODUCTION: Although dolutegravir (DTG) is deemed stable, safe, cost-effective, and clinically beneficial, it also carries the risk of side effects, including observed weight gain among patients on DTG-based antiretroviral therapy (ART) regimens. We compared weight changes among adults (≥18 years) initiating tenofovir disoproxil fumarate, lamivudine, and dolutegravir (TLD) or tenofovir disoproxil fumarate, emtricitabine, and efavirenz (TEE) regimens and those switching from TEE to TLD (TEE-to-TLD switchers) in three large primary care facilities in South Africa METHODS: We conducted a retrospective longitudinal record review using patient medical records, extracting relevant demographic and clinical data from October 2018 to June 2021 from randomly selected adults who initiated TLD or TEE (initiators) and adult TEE-to-TLD switchers. We assessed weight, body mass index (BMI), and percentage weight changes for both groups and fitted linear regression and generalized linear models to determine factors associated with weight and BMI change and percentage weight change ≥10%, respectively, among treatment initiators. We fitted linear mixed-effect models among TEE-to-TLD switchers to consider repeated measures. RESULTS: Of 860 initiators, 450 (52.3%) initiated on TEE and 410 (47.7%) on TLD, with median follow-up of 1.4 years and 1.0 year, respectively. At initiation, 43.3% on TEE and 40.8% on TLD were overweight or obese. TLD initiators had an adjusted higher mean weight gain of 1.6 kg (p < 0.001) and mean BMI gain of 0.51 kg/m2 (p < 0.001) than TEE initiators. Independent risk factors for higher mean weight and BMI included age ≥50 years, male, on ART for >12 months, initial BMI of <18.5 kg/m2, and CD4 counts <200 cells/µL. Of 298 TEE-to-TLD switchers, 36.6% were overweight or obese at TEE initiation. Comparing before and after TLD switch, TEE-to-TLD switchers had an adjusted mean weight of 1.2 kg less while on TLD (p = 0.026). Being overweight and CD4 counts >350 cells/µL were independent risk factors for lower weight gain after TLD switch. CONCLUSIONS: We report more weight gain among TLD than among TEE initiators, although to a lesser extent than previously reported. TEE-to-TLD switchers experienced less weight gain after TLD switch; return to health before receiving TLD may be a contributory factor. The current findings are reassuring for those switching to a DTG-based regimen.

Implementation preferences for the management of sexually transmitted infections in the South African health system: a discrete choice experiment.

OBJECTIVES: Despite strengthening HIV prevention with the introduction of pre-exposure prophylaxis (PrEP), STI services have remained relatively unchanged and the standard of care remains syndromic management. We used a discrete choice experiment to investigate service users' preferences for the diagnosis and treatment of STIs in South Africa. METHODS: Between 1 March 2021 and 20 April 2021, a cross-sectional online questionnaire hosted on REDCap was administered through access links sent to WhatsApp support groups for HIV PrEP users and attendees of two primary healthcare clinics and two mobile facilities in the Eastern Cape and Gauteng provinces aged between 18 and 49 years. Participants either self-completed the questionnaire or received support from a research assistant. We used a conditional logit model for the initial analysis and latent class model (LCM) to establish class memberships, with results displayed as ORs and probabilities. RESULTS: We enrolled 496 individuals; the majority were female (69%) and <30 years (74%). The LCM showed two distinct groups. The first group, comprising 68% of the participants, showed a strong preference for self-sampling compared with no sampling (OR 2.16, 95% CI 1.62 to 2.88). A clinic follow-up appointment for treatment was less preferable to same-day treatment (OR 0.78, 95% CI 0.63 to 0.95). Contact slip from index patient (OR 0.86, 95% CI 0.76 to 0.96) and healthcare professional (HCP)-initiated partner notification (OR 0.63, 95% CI 0.55 to 0.73) were both less preferable than expedited partner treatment (EPT). The second group included 32% of participants with a lower preference for self-sampling compared with no sampling (OR 0.65, 95% CI 0.41 to 1.04). There was no treatment option that was significantly different from the others; however, there was a strong preference for HCP-initiated partner notification to EPT (OR 1.53, 95% CI 1.10 to 2.12). CONCLUSIONS: Our results suggest that service users preferred STI testing prior to treatment, with the majority preferring self-taken samples and receiving aetiology-based treatment on the same day.

Dexamethasone for Cardiac Surgery: A Practice Preference-Randomized Consent Comparative Effectiveness Trial.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. Our primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. Our secondary aim was to evaluate efficiency, value and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across 7 hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone, 1 mg/kg, or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (>48 h), sepsis, renal failure, myocardial infarction, stroke and death. RESULTS: Of 2093 patients assessed for eligibility, 1951 were randomized (median age 63 years, 80% male). The median number of home days was 23.0 (IQR, 20.1 to 24.1) in the dexamethasone group and 23.1 (IQR, 20.1 to 24.6) in the no dexamethasone group; median difference 0.1 (95% CI, -0.3 to 0.5), P=0.66. The rates of prolonged mechanical ventilation, RR 0.72 (95% CI, 0.48 to 1.08), sepsis, RR 1.02 (95% CI, 0.57 to 1.82), renal failure, RR 0.94 (95% CI, 0.80 to 1.12), myocardial infarction, RR 1.20 (95% CI, 0.30 to 4.82), stroke, RR 1.06 (95% CI, 0.54 to 2.08), and death, RR 0.72 (95% CI, 0.22 to 2.35), were comparable between groups (all P>0.10). Dexamethasone reduced intensive care unit stay, median 29 (IQR, 22 to 50) h vs. 43 (24 to 72) h, P=0.004. Our novel trial design was highly efficient (89.3% enrolment). CONCLUSIONS: Among patients undergoing cardiac surgery, high-dose dexamethasone decreased intensive care unit stay but did not increase the number of home days after surgery.

Infections in inflammatory bowel disease patients on immunomodulator and biologic therapy are not associated with high serum drug levels.

BACKGROUND: Inflammatory bowel disease (IBD) therapies now utilise higher doses of immunomodulatory and biologic therapies, predisposing patients to an increased risk of infections. AIMS: We aimed to determine whether infections were associated with high anti-tumour necrosis factor (TNF) drug levels in IBD and to quantify the risk and consequences of infections. METHODS: Two retrospective studies were performed, a descriptive cohort study and a matched case-control study. For the matched case-control study, cases of infection occurring on anti-TNF agents were matched in a 1:2 ratio to controls of anti-TNF treated patients without infections. RESULTS: In the descriptive study, 76 infections occurred in 60 patients, including 49 bacterial, 24 viral, four fungal and four parasitic. Of these, 61 (80.3%) were on biologics, 49 (64.5%) on immunomodulators and 11 (14.5%) on corticosteroids. Thirty-four (44.7%) were on combination therapy, 27 (35.5%) on biologic monotherapy and 15 (19.7%) on immunomodulator monotherapy. Median anti-TNF drug levels in infection cases were 3.9 µg/mL for infliximab and 6.0 µg/mL for adalimumab. In the case-control study, 32 cases of infection in 27 anti-TNF treated patients were matched with 64 anti-TNF treated controls without infections. Among infection cases, 59.5% were on combination therapy versus 40.6% on biologic monotherapy (P = 0.59). Median drug levels for cases and controls respectively were 3.9 µg/mL versus 5.5 µg/mL for infliximab (P = 0.72) and 6.0 µg/mL versus 9.9 µg/mL for adalimumab (P = 0.34). CONCLUSION: Infections in patients with IBD were common, and the risk was highest with combination therapy. Infections were not associated with high serum anti-TNF levels.

Developmental milestones in captive Galago moholi.

Systems of the body develop in a modular manner. For example, neural development in primates is generally rapid, whereas dental development varies much more. In the present study, we examined development of the skull, teeth, and postcrania in a highly specialized leaping primate, Galago moholi. Eighteen specimens ranging from birth to adult were studied. Bones, teeth, and the cranial cavity (i.e., endocast) were reconstructed with Amira software based on microCT cross-referenced to histology. Amira was also used to compute endocast volume (as a proxy for brain size). Reconstructions of the wrist and ankle show that ossification is complete at 1 month postnatally, consistent with the onset of leaping locomotion in this species. Endocranial volume is less than 50% of adult volume at birth, ~80% by 1 month, and has reached adult volume by 2 months postnatal age. Full deciduous dentition eruption occurs by 2 weeks, and the young are known to begin capturing and consuming arthropods on their own by 4 weeks, contemporaneous with the timing of bone and ankle ossification that accompanies successful hunting. The modular pattern of development of body systems in Galago moholi provides an interesting view of a "race" to adult morphology for some joints that are critical for specialized leaping and clinging, rapid crown mineralization to begin a transitional diet, but perhaps more prolonged reliance on nursing to support brain growth.

Dexamethasone and persistent wound pain: a prespecified analysis of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial.

BACKGROUND: Dexamethasone is commonly administered intraoperatively to prevent postoperative nausea and vomiting and is believed to have analgesic properties. It is unknown whether it has an impact on chronic wound pain. METHODS: In this prespecified embedded superiority substudy of the randomised PADDI trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and were followed up for 6 months postoperatively. The primary outcome was the incidence of pain in the surgical wound at 6 months. Secondary outcomes included acute postoperative pain and correlates of chronic postsurgical pain. RESULTS: We included 8478 participants in the modified intention-to-treat population (4258 in the dexamethasone group and 4220 in the matched placebo group). The primary outcome occurred in 491 subjects (11.5%) in the dexamethasone arm and 404 (9.6%) subjects in the placebo arm (relative risk 1.2, 95% confidence interval 1.06-1.41, P=0.003). Maximum pain scores at rest and on movement in the first 3 postoperative days were lower in the dexamethasone group compared with the control group {median 5 (inter-quartile range [IQR] 3.0-8.0) vs 6 (IQR 3.0-8.0) and median 7 (IQR 5.0-9.0) vs 8 (IQR 6.0-9.0), P<0.001 for both}. Severity of postoperative pain was not predictive of chronic postsurgical pain. The severity of chronic postsurgical pain and the frequency of neuropathic features did not differ between treatment groups. CONCLUSION: Administration of dexamethasone 8 mg i.v. was associated with an increase in the risk of pain in the surgical wound 6 months after surgery. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Preferences, educational messaging, and demand creation channels for multipurpose-prevention technologies (MPTs) among women in South Africa.

BACKGROUND: South African women, including female sex workers (FSWs), are disproportionately affected by HIV, experience a high unmet need for contraception and high rates of sexually transmitted infections (STIs). Products that address the interlinked risk between HIV, unplanned pregnancy, and other STIs are needed. There are several multipurpose-prevention technologies (MPTs) in development, aimed at preventing both HIV and pregnancy. This study aimed to explore educational messaging and demand creation channels to improve the potential uptake of a hypothetical MPT implant, using participatory action research. It also aimed to look at product and service provision attributes preferred by potential end users. METHODS: Between July and August 2022, 303 PrEP-eligible adolescent girls and young women (AGYW) (18-24 years), women > 24 years, and FSW's (≥ 18 years) participated in 4-hour workshops, where they were asked about their ideal messaging and demand creation channels and their preferences for different attributes of an MPT implant. Quantitative descriptive analysis was conducted to determine the frequency and ranking for each demand creation message, channel, and each product and service provision attribute, by population group. A chi-square test was used to assess MPT implant characteristics associated with age. Qualitative data were analysed using deductive and thematic analysis. RESULTS: A total of 104 AGYW, 157 women > 24 years, and 42 FSWs participated in the PAR workshops. Participants preferred demand creation messages that were empowering, motivational and encouraged body autonomy. The use of slang was popular. Community radio stations and newspapers, social media, and information at hospitals and clinics were participants' preferred MPT demand creation channels because they were easily accessible. Providing long-term and dual HIV and pregnancy protection, receiving implant services at the local clinic, manageable side effects, discreet and private implant, and numbing the area before insertion and removal, were the most preferred product and service provision attributes. CONCLUSION: Early considerations for women's product preferences are key to product development. Educational messaging around the MPT implant should be empowering and in local languages, this may motivate women to learn more about it and use it. Multiple demand creation channels should be used to engage both young and older populations, which may ensure better reach.

A morphometric analysis of early Eocene Euprimate tarsals from Gujarat, India.

Early Eocene primate postcranial bones from the Vastan lignite mine of Gujarat, India, have proven useful for understanding the haplorhine and strepsirrhine divergence. Previous analyses of material assigned to Asiadapidae supported interpretations that these primates were generalized arboreal quadrupeds, while the omomyid Vastanomys was likely to have been more proficient leaper than asiadapids. More recent examinations of long bone cross-sectional properties and calcaneal elongation have complicated the behavioral interpretations of these fossils. This study examines whole talar and calcaneal morphology of the Vastan material to refine the locomotor reconstructions of these fossils. A comparative sample of extant primate species representing various locomotor behaviors was obtained by accessing surface models from MorphoSource.org. Surface models of fossil specimens attributed to Asiadapis cambayensis, Marcgodinotius indicus, and Vastanomys major were generated from micro-computed tomography scans. A morphological analysis was carried out using weighted spherical harmonics, a Fourier-based method that represents surfaces using coefficients associated with a common set of spherical harmonic functions. The coefficients describing each surface were then used as shape variables in a principal components analysis. Significant differences between locomotor groups were assessed using nonparametric tests. Results from extant comparative samples show that locomotor behavior can be predicted from both talar and calcaneal morphology when phylogenetic relationships are known. Consistent with previous analyses, our results indicate that Asiadapis cambayensis and Marcgodinotius indicus were likely arboreal quadrupeds with some leaping capabilities. Vastanomys major is reconstructed as an arboreal quadruped with greater leaping proficiency than its asiadapid counterparts based on its talar morphology.

Dexamethasone and clinically significant postoperative nausea and vomiting: a prespecified substudy of the randomised perioperative administration of dexamethasone and infection (PADDI) trial.

BACKGROUND: Clinically significant postoperative nausea and vomiting (PONV) is a patient-reported outcome which reflects patient experience. Although dexamethasone prevents PONV, it is unknown what impact it has on this experience. METHODS: In this prespecified embedded superiority substudy of the randomised Perioperative Administration of Dexamethasone and Infection (PADDI) trial, patients undergoing non-urgent noncardiac surgery received dexamethasone 8 mg or placebo intravenously after induction of anaesthesia, and completed a validated PONV questionnaire. The primary outcome was the incidence of clinically significant PONV on day 1 or day 2 postoperatively. Secondary outcomes included the incidence of clinically significant PONV and severe PONV on days 1 and 2 considered separately. RESULTS: A total of 1466 participants were included, with 733 patients allocated to the dexamethasone arm and 733 to matched placebo. The primary outcome occurred in 52 patients (7.1%) in the dexamethasone arm and 66 (9%) patients in the placebo arm (relative risk [RR]=0.79; 95% confidence interval [CI], 0.56-1.11; P=0.18). Severe PONV occurred on day 2 in 27 patients (3.9%) in the dexamethasone arm and 47 patients (6.7%) in the placebo arm (RR=0.58; 95% CI, 0.37-0.92; P=0.02; number needed-to-treat (NNT)=36.7; 95% CI, 20-202). In the entire cohort of 8880 PADDI patients, lower nausea scores, less frequent administration of antiemetics, and fewer vomiting events were recorded by patients in the dexamethasone arm up to day 2 after surgery. CONCLUSIONS: Administration of dexamethasone 8 mg i.v. did not influence clinically significant PONV. Dexamethasone administration did, however, decrease the incidence and severity of PONV, and was associated with less frequent administration of antiemetic agents. CLINICAL TRIAL REGISTRATION: ACTRN12614001226695.

Inclusion, characteristics, and outcomes of male and female participants in large international perioperative studies.

BACKGROUND: We compared baseline characteristics and outcomes and evaluated the subgroup effects of randomised interventions by sex in males and females in large international perioperative trials. METHODS: Nine randomised trials and two cohort studies recruiting adult patients, conducted between 1995 and 2020, were included. Baseline characteristics and outcomes common to six or more studies were evaluated. Regression models included terms for sex, study, and an interaction between the two. Comparing outcomes without adjustment for baseline characteristics represents the 'total effect' of sex on the outcome. RESULTS: Of 54 626 participants, 58% were male and 42% were female. Females were less likely to have ASA physical status ≥3 (56% vs 64%), to smoke (15% vs 23%), have coronary artery disease (21% vs 32%), or undergo vascular surgery (10% vs 23%). The pooled incidence of death was 1.6% in females and 1.8% in males (risk ratio [RR] 0.92; 95% confidence interval [CI]: 0.81-1.05; P=0.20), of myocardial infarction was 4.2% vs 4.5% (RR 0.92; 95% CI: 0.81-1.03; P=0.10), of stroke was 0.5% vs 0.6% (RR 1.03; 95% CI: 0.79-1.35; P=0.81), and of surgical site infection was 8.6% vs 8.3% (RR 1.03; 95% CI: 0.79-1.35; P=0.70). Treatment effects of three interventions demonstrated statistically significant effect modification by sex. CONCLUSIONS: Females were in the minority in all included studies. They were healthier than males, but outcomes were comparable. Further research is needed to understand the reasons for this discrepancy. CLINICAL TRIAL REGISTRATION: International Registry of Meta-Research (UID: IRMR_000011; 5 January 2021).

Postoperative anaemia and patient-centred outcomes after major abdominal surgery: a retrospective cohort study.

BACKGROUND: Compared with anaemia before surgery, the underlying pathogenesis and implications of postoperative anaemia are largely unknown. METHODS: This retrospective cohort study analysed prospective data obtained from 2983 adult patients across 47 centres enrolled in a clinical trial evaluating restrictive and liberal intravenous fluids. The primary endpoint was persistent disability or death up to 90 days after surgery. Secondary endpoints included major septic complications, hospital stay, and patient quality of recovery using a 15-item quality of recovery (QoR-15) score, hospital re-admissions, and disability-free survival up to 12 months after surgery. Anaemia and disability were defined according to the WHO definitions. Multivariable regression was used to adjust for baseline risk and surgery. RESULTS: A total of 2983 patients met inclusion criteria for this study, of which 78.5% (95% confidence interval [CI], 76.7-80.1%) had postoperative anaemia. Patients with postoperative anaemia had a higher adjusted risk of death or disability up to 90 days after surgery when compared with those without anaemia: 18.2% vs 9.2% (risk ratio [RR]=1.51; 95% CI, 1.10-2.07, P=0.011); lower QoR-15 scores on Day 3 and Day 30, 105 (95% CI, 87-119) vs 114 (95% CI, 99-128; P<0.001), and 130 (95% CI, 112-140) vs 139 (95% CI, 121-144; P<0.011), respectively; higher adjusted risk of a composite of mortality/septic complications, 2.01 (95% CI, 1.55-42.67; P<0.001); unplanned admission to ICU (RR=2.65; 95% CI, 1.65-4.23; P<0.001); and longer median (inter-quartile range [IQR]) hospital stays, 6.6 (4.4-12.4) vs 3.7 (2.5-6.5) days (P<0.001). CONCLUSIONS: Postoperative anaemia is common and is independently associated with poor outcomes after surgery. Optimal prevention and treatment strategies need to be investigated. CLINICAL TRIAL REGISTRATION: NCT04978285 (ClinicalTrials.gov).

Outcomes of non-cystic fibrosis-related bronchiectasis post-lung transplantation.

BACKGROUND: Lung transplantation is a recognised treatment for end-stage lung disease due to bronchiectasis. Non-cystic fibrosis (CF) bronchiectasis and CF are often combined into one cohort; however, outcomes for non-CF bronchiectasis patients vary between centres, and in comparison with those for CF. AIMS: To compare lung transplantation mortality and morbidity of bronchiectasis (non-CF) patients with those with CF and other indications. METHODS: Retrospective analysis of patients undergoing lung transplantation between 1 January 2008 and 31 December 2013. Time to and cause of lung allograft loss was censored on 1 April 2018. A case-note review was conducted on a subgroup of 78 patients, to analyse hospital admissions as a marker of morbidity. RESULTS: A total of 341 patients underwent lung transplantation; 22 (6%) had bronchiectasis compared with 69 (20%) with CF. The 5-year survival for the bronchiectasis group was 32%, compared with CF (69%), obstructive lung disease (OLD) (64%), pulmonary hypertension (62%) and ILD (55%) (P = 0.008). Lung allograft loss due to chronic lung allograft dysfunction with predominant infection was significantly higher in the bronchiectasis group at 2 years. The rate of acute admissions was 2.24 higher in the bronchiectasis group when compared with OLD (P = 0.01). Patients with bronchiectasis spent 45.81 days in hospital per person year after transplantation compared with 18.21 days for CF. CONCLUSIONS: Bronchiectasis patients in the present study had a lower 5-year survival and poorer outcomes in comparison with other indications including CF. Bronchiectasis should be considered a separate entity to CF in survival analysis.

Frequency of Diarrhea, Stool Specimen Collection and Testing, and Detection of Clostridioides Difficile Infection Among Hospitalized Adults in the Muenster/Coesfeld Area, Germany.

Clostridioides difficile infection (CDI) often manifests as diarrhea, particularly in adults of older age or with underlying comorbidities. However, only severe cases are notifiable in Germany. Moreover, failure to collect a stool specimen from inpatients with diarrhea or incomplete testing may lead to underdiagnosis and underreporting of CDI. We assessed the frequency of diarrhea, stool specimen collection, and CDI testing to estimate CDI underdiagnosis and underreporting among hospitalized adults. In a ten-day point-prevalence study (2019-2021) of nine hospitals in a defined area (Muenster/Coesfeld, North Rhine-Westphalia, Germany), all diarrhea cases (≥ 3 loose stools in 24 h) among adult inpatients were captured via medical record screening and nurse interviews. Patient characteristics, symptom onset, putative origin, antibiotic consumption, and diagnostic stool sampling were collected in a case report form (CRF). Diagnostic results were retrieved from the respective hospital laboratories. Among 6998 patients screened, 476 (7%) diarrhea patients were identified, yielding a hospital-based incidence of 201 cases per 10,000 patient-days. Of the diarrheal patients, 186 (39%) had a stool sample collected, of which 160 (86%) were tested for CDI, meaning that the overall CDI testing rate among diarrhea patients was 34%. Toxigenic C. difficile was detected in 18 (11%) of the tested samples. The frequency of stool specimen collection and CDI testing among hospitalized diarrhea patients was suboptimal. Thus, CDI incidence in Germany is likely underestimated. To assess the complete burden of CDI in German hospitals, further investigations are needed.

Identifying Conversational Strategies for Psychiatrists in Discussing Substance Use with Adolescent Patients.

Child and adolescent psychiatrists are uniquely positioned to discuss substance use with high risk patients; however, there has been little research about these conversations and their characteristics. To identify communication strategies for navigating conversations about substance use with adolescent patients, we conducted 21 in-depth interviews with practicing child and adolescent psychiatrists. Findings from this study identify four strategies that child and adolescent psychiatrists reported as being successful: expressing empathy, avoiding resistance, honoring autonomy, and managing family involvement. In addition to describing these strategies, we briefly describe a theoretical framework that might help to explain the perceived success of these strategies, and we offer recommendations for how to apply our findings to improve psychiatric practice.

Effect of Lower vs Higher Oxygen Saturation Targets on Survival to Hospital Discharge Among Patients Resuscitated After Out-of-Hospital Cardiac Arrest: The EXACT Randomized Clinical Trial.

Importance: The administration of a high fraction of oxygen following return of spontaneous circulation in out-of-hospital cardiac arrest may increase reperfusion brain injury. Objective: To determine whether targeting a lower oxygen saturation in the early phase of postresuscitation care for out-of-hospital cardiac arrest improves survival at hospital discharge. Design, Setting, and Participants: This multicenter, parallel-group, randomized clinical trial included unconscious adults with return of spontaneous circulation and a peripheral oxygen saturation (Spo2) of at least 95% while receiving 100% oxygen. The trial was conducted in 2 emergency medical services and 15 hospitals in Victoria and South Australia, Australia, between December 11, 2017, and August 11, 2020, with data collection from ambulance and hospital medical records (final follow-up date, August 25, 2021). The trial enrolled 428 of a planned 1416 patients. Interventions: Patients were randomized by paramedics to receive oxygen titration to achieve an oxygen saturation of either 90% to 94% (intervention; n = 216) or 98% to 100% (standard care; n = 212) until arrival in the intensive care unit. Main Outcomes and Measures: The primary outcome was survival to hospital discharge. There were 9 secondary outcomes collected, including hypoxic episodes (Spo2 <90%) and prespecified serious adverse events, which included hypoxia with rearrest. Results: The trial was stopped early due to the COVID-19 pandemic. Of the 428 patients who were randomized, 425 were included in the primary analysis (median age, 65.5 years; 100 [23.5%] women) and all completed the trial. Overall, 82 of 214 patients (38.3%) in the intervention group survived to hospital discharge compared with 101 of 211 (47.9%) in the standard care group (difference, -9.6% [95% CI, -18.9% to -0.2%]; unadjusted odds ratio, 0.68 [95% CI, 0.46-1.00]; P = .05). Of the 9 prespecified secondary outcomes collected during hospital stay, 8 showed no significant difference. A hypoxic episode prior to intensive care was observed in 31.3% (n = 67) of participants in the intervention group and 16.1% (n = 34) in the standard care group (difference, 15.2% [95% CI, 7.2%-23.1%]; OR, 2.37 [95% CI, 1.49-3.79]; P < .001). Conclusions and Relevance: Among patients achieving return of spontaneous circulation after out-of-hospital cardiac arrest, targeting an oxygen saturation of 90% to 94%, compared with 98% to 100%, until admission to the intensive care unit did not significantly improve survival to hospital discharge. Although the trial is limited by early termination due to the COVID-19 pandemic, the findings do not support use of an oxygen saturation target of 90% to 94% in the out-of-hospital setting after resuscitation from cardiac arrest. Trial Registration: ClinicalTrials.gov Identifier: NCT03138005.

COVID-19 Pandemic Impact on Percutaneous Coronary Intervention for Acute Coronary Syndromes: An Australian Tertiary Centre Experience.

BACKGROUND: Countries who suffered large COVID-19 outbreaks reported a decrease in acute coronary syndrome (ACS) presentations and percutaneous coronary intervention (PCI). The impact of the pandemic in countries like Australia, with relatively small outbreaks yet significant social restrictions, is relatively unknown. There is also limited and conflicting data regarding the impact on clinical outcomes, symptom-to-door time (STDT) and door-to-balloon time (DTBT). METHODS: Consecutive ACS patients treated with PCI were prospectively recruited from a tertiary hospital network in Melbourne, Australia. The pre-pandemic period (11 March 2019-10 March 2020) was compared to the pandemic period (11 March 2020-10 May 2020) using an interrupted time series analysis with a primary endpoint of number PCI-treated ACS per day. Secondary endpoints included STDT, DTBT, total mortality and major adverse cardiac events (MACE). RESULTS: A total 984 ACS patients (14.8% during the pandemic period) received PCI. Mean number of PCI-treated ACS per day did not differ between the two periods (2.3 vs 2.4, p=0.61) with no difference in STDT [+51.3 mins, 95% confidence interval (CI) -52.4 to 154.9, p=0.33], 30-day mortality (5% vs 5.3%, p=0.86) or MACE (5.2% vs 6.1%, p=0.68). DTBT was significantly longer during the pandemic versus the pre-pandemic period (+18.1 mins, 95% CI 1.6-34.5, p=0.03) and improved with time (slope estimate: -0.76, 95% CI -1.62 to 0.10). CONCLUSIONS: Despite significant social restrictions imposed in Melbourne, numbers of ACS treated with PCI and 30-day outcomes were similar to pre-pandemic times. DTBT was significantly longer during the COVID-19 pandemic period, likely reflecting infection control measures, which reassuringly improved with time.

Trajectory and Predictors of Mental Health Symptoms and Wellbeing in Newly Admitted Nursing Home Residents.

OBJECTIVES: This study determined changes in multiple aspects of mental health and wellbeing in newly admitted nursing home residents, and identified risk and protective factors. METHODS: Participants were 204 residents recently admitted to one of 42 nursing homes in Melbourne, Australia. A subgroup of 82 participants were followed up eight months post-admission. Depression, anxiety, stress, adjustment, and quality of life were assessed at baseline and follow-up. Predictive factors (demographics, health, transition factors, nursing home characteristics) were examined in multiple regression analyses. RESULTS: Rates of depression and anxiety were high at both baseline and follow-up. Low self-rated health and medical comorbidity predicted poor wellbeing at baseline. Higher perceived control in the relocation to the nursing home and engagement in meaningful activities were associated with better post-admission outcomes. Baseline psychotropic medication use predicted lower anxiety at follow-up but did not impact depressive symptoms. CONCLUSIONS: There were no significant changes in mental health and wellbeing from one to eight months post-admission. The negative effect of residing in a for-profit nursing home requires further investigation. CLINICAL IMPLICATIONS: Individual activity scheduling and an opportunity to participate in relocation decision-making and planning may support resident wellbeing post-admission.

Orai1 Channel Inhibition Preserves Left Ventricular Systolic Function and Normal Ca2+ Handling After Pressure Overload.

BACKGROUND: Orai1 is a critical ion channel subunit, best recognized as a mediator of store-operated Ca2+ entry (SOCE) in nonexcitable cells. SOCE has recently emerged as a key contributor of cardiac hypertrophy and heart failure but the relevance of Orai1 is still unclear. METHODS: To test the role of these Orai1 channels in the cardiac pathophysiology, a transgenic mouse was generated with cardiomyocyte-specific expression of an ion pore-disruptive Orai1R91W mutant (C-dnO1). Synthetic chemistry and channel screening strategies were used to develop 4-(2,5-dimethoxyphenyl)-N-[(pyridin-4-yl)methyl]aniline (hereafter referred to as JPIII), a small-molecule Orai1 channel inhibitor suitable for in vivo delivery. RESULTS: Adult mice subjected to transverse aortic constriction (TAC) developed cardiac hypertrophy and reduced ventricular function associated with increased Orai1 expression and Orai1-dependent SOCE (assessed by Mn2+ influx). C-dnO1 mice displayed normal cardiac electromechanical function and cellular excitation-contraction coupling despite reduced Orai1-dependent SOCE. Five weeks after TAC, C-dnO1 mice were protected from systolic dysfunction (assessed by preserved left ventricular fractional shortening and ejection fraction) even if increased cardiac mass and prohypertrophic markers induction were observed. This is correlated with a protection from TAC-induced cellular Ca2+ signaling alterations (increased SOCE, decreased [Ca2+]i transients amplitude and decay rate, lower SR Ca2+ load and depressed cellular contractility) and SERCA2a downregulation in ventricular cardiomyocytes from C-dnO1 mice, associated with blunted Pyk2 signaling. There was also less fibrosis in heart sections from C-dnO1 mice after TAC. Moreover, 3 weeks treatment with JPIII following 5 weeks of TAC confirmed the translational relevance of an Orai1 inhibition strategy during hypertrophic insult. CONCLUSIONS: The findings suggest a key role of cardiac Orai1 channels and the potential for Orai1 channel inhibitors as inotropic therapies for maintaining contractility reserve after hypertrophic stress.