PET-CT-guided versus CT-guided biopsy in suspected malignant pleural thickening: a randomised trial.

BACKGROUND: Pleural biopsy is the gold standard for diagnosis of pleural malignancy but a significant proportion will have an inconclusive biopsy despite ongoing clinical suspicion of malignancy. We investigated whether positron emission tomography-computed tomography (PET-CT) targeted pleural biopsy is superior to standard CT-guided pleural biopsy following an initial non-diagnostic biopsy. METHODS: The TARGET trial was a multicentre, parallel group randomised trial. Patients with a previous inconclusive pleural biopsy but an ongoing suspicion of pleural malignancy were randomised (1:1) to receive either CT-guided biopsy (standard care) or PET-CT followed by a targeted CT biopsy (intervention). The primary outcome was pleural malignancy correctly identified from the trial biopsy. RESULTS: Between September 2015 and September 2018, 59 participants were randomised from eight UK hospital sites: 29 to CT-only followed by targeted biopsy and 30 to PET-CT followed by targeted biopsy. The proportion of pleural malignancy correctly identified was similar between the groups (risk ratio 1.03 (95% CI 0.83-1.29); p=0.77). The sensitivity of the trial biopsy to identify pleural malignancy was 79% (95% CI 54-94%) in the CT-only group versus 81% (95% CI 54-96%) in the PET-CT group. CONCLUSIONS: The results do not support the practice of PET-CT to guide pleural biopsies in patients with a previous non-diagnostic biopsy. The diagnostic sensitivity in the CT-only group was higher than anticipated and supports the practice of repeating a CT-guided biopsy following an inconclusive result if clinical suspicion of malignancy persists.

A feasibility randomised trial comparing therapeutic thoracentesis to chest tube insertion for the management of pleural infection: results from the ACTion trial.

BACKGROUND: Pleural infection is a complex condition with a considerable healthcare burden. The average hospital stay for pleural infection is 14 days. Current standard of care defaults to chest tube insertion and intravenous antibiotics. There have been no randomised trials on the use of therapeutic thoracentesis (TT) for pleural fluid drainage in pleural infection. AIMS AND OBJECTIVES: To assess the feasibility of a full-scale trial of chest tube vs TT for pleural infection in a single UK centre. The primary outcome was defined as the acceptability of randomisation to patients. METHODS: Adult patients admitted with a pleural effusion felt to be related to infection and meeting criteria for drainage (based on international guidelines) were eligible for randomisation. Participants were randomised (1:1) to chest tube insertion or TT with daily review assessing need for further drainages or other therapies. Neither participant nor clinician were blinded to treatment allocation. Patients were followed up at 90 days post-randomisation. RESULTS: From September 2019 to June 2021, 51 patients were diagnosed with pleural infection (complex parapneumonic effusion/empyema). Eleven patients met the inclusion criteria for trial and 10 patients were randomised (91%). The COVID-19 pandemic had a substantial impact on recruitment. Data completeness was high in both groups with no protocol deviations. Patients randomised to TT had a significantly shorter overall mean hospital stay (5.4 days, SD 5.1) compared to the chest tube control group (13 days, SD 6.0), p = 0.04. Total number of pleural procedures required per patient were similar, 1.2 in chest tube group and 1.4 in TT group. No patient required a surgical referral. Adverse events were similar between the groups with no readmissions related to pleural infection. CONCLUSIONS: The ACTion trial met its pre-specified feasibility criteria for patient acceptability but other issues around feasibility of a full-scale trial remain. From the results available the hypothesis that TT can reduce length of stay in pleural infection should be explored further. TRIAL REGISTRATION: ISRCTN: 84674413.

Depression and anxiety during the perinatal period.

BACKGROUND: Mood and anxiety and related disorders (AD) account for a significant proportion of mental health conditions, with close to 30 % of the population (28.8 %) suffering from an AD at some time in their life, and over fifteen percent (16.2 %) suffering from a mood disorder. The existing empirical literature leaves a number of important gaps with respect to our understanding of mood, anxiety and stress related difficulties among pregnant and postpartum women. The objective of this research is to address these. METHODS: Participants were 660 English-speaking pregnant women. Participants for the portion of the research estimating the prevalence/incidence of perinatal mood disorders and AD (N = 347) were recruited proportionally from a geographically defined area. All participants were recruited via prenatal clinic visits at hospitals, physician offices and midwifery clinics, and via community outreach at events and through word of mouth. Recruitment took place between November 9, 2007 and November 12, 2010. Participants were administered questionnaires prenatally at two time points (approximately 24 and 33 weeks gestation) and again at 4-6 weeks' postpartum and 6-months postpartum. Prevalence/incidence study participants who screened above cut-off on one or more of the 4-6 week mood and anxiety questionnaires were also administered a diagnostic interview for mood disorders and AD at approximately 8-12 weeks postpartum. DISCUSSION: This research addresses a number of gaps in our understanding of mood, anxiety and stress among pregnant and postpartum women. Specifically, gaps in our knowledge regarding the prevalence and incidence of (a) AD and mood disorders, and (b) anxiety and stress among women experiencing a medically high-risk pregnancy, interest in stress management training in pregnancy, mental health treatment barriers and access and screening for anxiety among pregnant and postpartum women are addressed. The findings from this series of studies have the potential to improve screening, assessment and treatment of mood and anxiety problems suffered by pregnant and postpartum women.

Enabling a Learning Public Health System: Enhanced Surveillance of HIV and Other Sexually Transmitted Infections.

Sexually transmitted infections (STIs) continue to pose a substantial public health challenge in the United States (US). Surveillance, a cornerstone of disease control and prevention, can be strengthened to promote more timely, efficient, and equitable practices by incorporating health information exchange (HIE) and other large-scale health data sources into reporting. New York City patient-level electronic health record data between January 1, 2018 and June 30, 2023 were obtained from Healthix, the largest US public HIE. Healthix data were linked to neighborhood-level information from the American Community Survey. In this cross-sectional study, we compared patients who received a test or tested positive for chlamydia, gonorrhea, and/or HIV with patients who were untested or tested negative, respectively, using generalized estimating equations with logit function and robust standard errors. Among 1,519,121 tests performed for chlamydia, 1,574,772 for gonorrhea, and 1,200,560 for HIV, 2%, 0.6% and 0.3% were positive for chlamydia, gonorrhea, and HIV, respectively. Chlamydia and gonorrhea co-occurred in 1,854 cases (7% of chlamydia and 21% of gonorrhea total cases). Testing behavior was often incongruent with geographic and sociodemographic patterns of positive cases. For example, people living in areas with the highest levels of poverty were less likely to test for gonorrhea but almost twice as likely to test positive compared to those in low poverty areas. Regional HIE enabled review of testing and cases using granular and complementary data not typically available given existing reporting practices. Enhanced surveillance spotlights potential incongruencies between testing patterns and STI risk in certain populations, signaling potential under- and over-testing. These and future insights derived from HIE data may be used to continuously inform public health practice and drive further improvements in provision and evaluation of services and programs.

Development of Machine Learning-Based Mpox Surveillance Models in a Learning Health System.

We developed machine learning and deep learning models to identify mpox cases from clinical notes as part of a learning health system initiative. Lasso regression outperformed deep learning models, excelled in minimizing false positives, and may prove helpful for flagging missed or delayed diagnoses as part of continuous quality improvement.

Computational modeling of heart failure in microgravity transitions.

The space tourism industry is growing due to advances in rocket technology. Privatised space travel exposes non-professional astronauts with health profiles comprising underlying conditions to microgravity. Prior research has typically focused on the effects of microgravity on human physiology in healthy astronauts, and little is known how the effects of microgravity may play out in the pathophysiology of underlying medical conditions, such as heart failure. This study used an established, controlled lumped mathematical model of the cardiopulmonary system to simulate the effects of entry into microgravity in the setting of heart failure with both, reduced and preserved ejection fraction. We find that exposure to microgravity eventuates an increased cardiac output, and in patients with heart failure there is an unwanted increase in left atrial pressure, indicating an elevated risk for development of pulmonary oedema. This model gives insight into the risks of space flight for people with heart failure, and the impact this may have on mission success in space tourism.

Improving quality in adult long covid services: Findings from the LOCOMOTION quality improvement collaborative.

The protracted form of COVID-19 known as 'long covid' was first described in 2020. Its symptoms, course and prognosis vary widely; some patients have a multi-system, disabling and prolonged illness. In 2021, ring-fenced funding was provided to establish 90 long covid clinics in England; some clinics were also established in Scotland and Wales. The NIHR-funded LOCOMOTION project implemented a UK-wide quality improvement collaborative involving ten of these clinics, which ran from 2021 to 2023. At regular online meetings held approximately 8-weekly, participants prioritised topics, discussed research evidence and guidelines, and presented exemplar case histories and clinic audits. A patient advisory group also held a priority-setting exercise, participated in quality meetings and undertook a service evaluation audit. The goal of successive quality improvement cycles aimed at changing practice to align with evidence was sometimes hard to achieve because definitive evidence did not yet exist in this new condition; many patients had comorbidities; and clinics were practically constrained in various ways. Nevertheless, much progress was made and a series of 'best practice' guides was produced, covering general assessment and management; breathing difficulties; orthostatic tachycardia and other autonomic symptoms; fatigue and cognitive impairment; and vocational rehabilitation. This paper summarises key findings with the frontline clinician in mind.

Using a Health Information Exchange to Characterize Changes in HIV Viral Load Suppression and Disparities During the COVID-19 Pandemic in New York City.

Background: HIV viral suppression requires sustained engagement in care. The COVID-19 pandemic challenged care accessibility for many people living with HIV (PLWH). We used health information exchange data to evaluate the effect of pandemic-related disruptions in HIV care on viral load suppression (VLS) and to examine racial/ethnic disparities in VLS. Methods: We performed a retrospective observational cohort study of PLWH using data from a regional health information exchange in the New York City region between 1 January 2018 and 31 December 2022. We established 2 cohorts: PLWH who received HIV care in 2020 (cohort A) and PLWH who did not receive HIV care in 2020 (cohort B). We categorized HIV VLS outcomes as suppressed or not suppressed and calculated the prevalence of VLS between 2018 and 2022. We compared proportions using chi-square tests and used unadjusted and adjusted logistic regression to estimate the association among variables, including race/ethnicity, cohort, and VLS. Results: Of 5 301 578 patients, 34 611 met our inclusion criteria for PLWH, 11 653 for cohort A, and 3141 for cohort B. In 2019, cohort B had a lower prevalence of VLS than cohort A (86% vs 89%, P < .001). Between 2019 and 2021, VLS dropped significantly among cohort B (86% to 81%, P < .001) while staying constant in cohort A (89% to 89%, P = .62). By 2022, members of cohort B were less likely than cohort A to be receiving HIV care in New York City (74% vs 88%, P < .001). Within both cohorts, Black and Hispanic patients had lower odds of VLS than White patients. Conclusions: In New York City, VLS remained high among PLWH who continued to receive care in 2020 and dropped among PLWH who did not receive care. VLS was lower among Black and Hispanic patients even after controlling for receipt of care.

The randomised thoracoscopic talc poudrage+indwelling pleural catheters versus thoracoscopic talc poudrage only in malignant pleural effusion trial (TACTIC): study protocol for a randomised controlled trial.

INTRODUCTION: Malignant pleural effusion (MPE) is common, with 50 000 new cases per year in the UK. MPE causes disabling breathlessness and indicates advanced disease with a poor prognosis. Treatment approaches focus on symptom relief and optimising quality of life (QoL). Patients who newly present with MPE commonly require procedural intervention for both diagnosis and therapeutic benefit.Thoracoscopic pleural biopsies are highly sensitive in diagnosing pleural malignancy. Talc poudrage may be delivered at thoracoscopy (TTP) to prevent effusion recurrence by effecting pleurodesis. Indwelling pleural catheters (IPCs) offer an alternative strategy for fluid control, enabling outpatient management and are often used as 'rescue' therapy following pleurodesis failure or in cases of 'trapped lung'. It is unknown whether combining a TTP with IPC insertion will improve patient symptoms or reduce time spent in the hospital.The randomised thoracoscopic talc poudrage + indwelling pleural catheters versus thoracoscopic talc poudrage only in malignant pleural effusion trial (TACTIC) is the first randomised controlled trial (RCT) to examine the benefit of a combined TTP and IPC procedure, evaluating cost-effectiveness and patient-centred outcomes such as symptoms and QoL. The study remains in active recruitment and has the potential to radically transform the pathway for all patients presenting with MPE. METHODS AND ANALYSIS: TACTIC is an unblinded, multicentre, RCT comparing the combination of TTP with an IPC to TTP alone. Co-primary outcomes are time spent in the hospital and mean breathlessness score over 4 weeks postprocedure. The study will recruit 124 patients and aims to define the optimal pathway for patients presenting with symptomatic MPE. ETHICS AND DISSEMINATION: TACTIC is sponsored by North Bristol NHS Trust and has been granted ethical approval by the London-Brent Research Ethics Committee (REC ref: 21/LO/0495). Publication of results in a peer-reviewed journal and conference presentations are anticipated. TRIAL REGISTRATION: ISRCTN 11058680.

Computational modeling of orthostatic intolerance for travel to Mars.

Astronauts in a microgravity environment will experience significant changes in their cardiopulmonary system. Up until now, there has always been the reassurance that they have real-time contact with experts on Earth. Mars crew however will have gaps in their communication of 20 min or more. In silico experiments are therefore needed to assess fitness to fly for those on future space flights to Mars. In this study, we present an open-source controlled lumped mathematical model of the cardiopulmonary system that is able simulate the short-term adaptations of key hemodynamic parameters to an active stand test after being exposed to microgravity. The presented model is capable of adequately simulating key cardiovascular hemodynamic changes-over a short time frame-during a stand test after prolonged spaceflight under different gravitational conditions and fluid loading conditions. This model can form the basis for further exploration of the ability of the human cardiovascular system to withstand long-duration space flight and life on Mars.

Video directly observed therapy for supporting and monitoring adherence to tuberculosis treatment in Uganda: a pilot cohort study.

INTRODUCTION: Nonadherence to treatment remains an obstacle to tuberculosis (TB) control worldwide. The aim of this study was to evaluate the feasibility of using video directly observed therapy (VDOT) for supporting TB treatment adherence in Uganda. METHODS: From May to December 2018, we conducted a pilot cohort study at a TB clinic in Kampala City. We enrolled patients aged 18-65 years with ≥3 months remaining of their TB treatment. Participants were trained to use a smartphone app to record videos of medication intake and submit them to a secured system. Trained health workers logged into the system to watch the submitted videos. The primary outcome was adherence measured as the fraction of expected doses observed (FEDO). In a secondary analysis, we examined differences in FEDO by sex, age, phone ownership, duration of follow-up, reasons for missed videos and patients' satisfaction at study exit. RESULTS: Of 52 patients enrolled, 50 were analysed. 28 (56%) were male, the mean age was 31 years (range 19-50 years) and 35 (70%) owned smartphones. Of the 5150 videos expected, 4231 (82.2%) were received. The median FEDO was 85% (interquartile range 66%-94%) and this significantly differed by follow-up duration. Phone malfunction, uncharged battery and VDOT app malfunctions were the commonest reasons for missed videos. 92% of patients reported being very satisfied with using VDOT. CONCLUSION: VDOT was feasible and acceptable for monitoring and supporting TB treatment. It resulted in high levels of adherence, suggesting that digital technology holds promise in improving patient monitoring in Uganda.

Gastrostomy tube placement by radiological versus endoscopic methods in an acute care setting: a retrospective review of frequency, indications, complications and outcomes.

OBJECTIVES: To describe the current practice of placing gastrostomy tubes (endoscopic and radiological), patient characteristics, indications for enteral support, complications and outcomes over a 13-month period, and explore factors that influenced complications and outcomes. Second, to provide Canadian data regarding feeding tube placement because no current literature reflecting these practices for Canadian hospitals is available. METHODS: Retrospective chart reviews were conducted. Patients who had initial percutaneous endoscopic gastrostomy (PEG) or percutaneous radiological gastrostomy (PRG) tubes inserted for nutritional purposes were included in the study. RESULTS: A total of 136 charts which included 30 PEG and 44 PRG procedures were reviewed. The PRG group was older than the PEG group (mean [+/-SD+/-5D; age 68+/-19 years versus 55+/-21 years, respectively; P=0.008). Patients in PEG group had longer lengths of hospital stay and more intensive care unit admissions than the PRG group (P=0.029). The main reason for tube insertion was dysphagia/aspiration (PEG [60%] and PRG [77%]). Minor complications were comparable between the two groups (P=0.678). There were three cases of major complications overall. More subjects in the PRG group died (18%) while in hospital than in the PEG group (3%) (P=0.055). No procedure-related deaths occurred in either group. CONCLUSIONS: Both methods of tube insertion provided a safe route for nutrition delivery despite a significant cost differential with PEGs costing 44% more than PRGs. Characteristics such as age, presence of ascites and severity of disease influenced the method of insertion despite the lack of current guidelines. Overall, the present study provides new descriptive data in a Canadian context.

Perinatal anxiety disorder prevalence and incidence.

BACKGROUND: Anxiety and related disorders (AD) disproportionately affect women, and are the most prevalent of all mental health conditions. The current research represents the first study of maternal postpartum AD prevalence in which all of the AD are assessed, and one of few studies of this type in which maternal prenatal AD incidence is assessed. METHODS: A Canadian sample of pregnant women (N=310) was recruited from a defined geographical area between November 2007 and November 2010. Participants were first administered postnatal mood and anxiety screening measures. Those who scored at or above cutoff on one or more of these measures were administered a diagnostic interview for depression and anxiety at approximately three months postpartum (n=115). Findings from the diagnostic interview were used to estimate the prevalence and incidence of mood and AD in pregnancy, as well as at and during the first three months postpartum. Period prevalence and incidence estimates were obtained retrospectively from interview data collected postnatally. RESULTS: The prevalence of AD during pregnancy and the early postpartum period (15.8% and 17.1% respectively) exceeded that of depression (3.9% and 4.8% respectively). The prevalence of OCD in our sample exceeded that of OCD among adults aged 18-64. Parity was unrelated to AD prevalence. Slightly less than 5% of participants were comorbid for both AD, and depression. LIMITATIONS: This study is limited by a relatively small sample size for a prevalence study, and non-random sample selection. As only women who scored above cutoff on one or more screening measures were interviewed, prevalence estimates are conservative. Finally, prenatal prevalence estimates are based on retrospective report provided postpartum. CONCLUSIONS: This study provides evidence that, as a group, anxiety and related conditions affect a significant proportion of postpartum women, and are more prevalent than is postpartum depression.

Abnormalities of the cadherin-catenin complex in chemically-induced colo-rectal carcinogenesis.

Beta-Catenin is a multifunctional protein originally identified as a component of the cadherin cell-cell adhesion complex. It also binds the adenomatous polyposis coli (APC) tumour suppressor which controls beta-catenin cellular levels through its degradation. (beta-Catenin and/or APC mutations result in increased cytoplasmic Beta-catenin and nuclear translocation. The aim of the present study was to examine the expression and cellular localisation of alpha and beta-catenin, p120 and E-cadherin in a chemically-induced mouse model of colo-rectal cancer using 1,2-dimethylhydrazine (DMH). Female Balb/C mice were injected subcutaneously with a solution providing 25 mg DMH base/kg body weight for 17 weeks. Animals were killed and tumours identified in the intestine with a dissecting microscope. Formalin-fixed paraffin-embedded sections of normal and dysplastic colonic mucosa were stained by an indirect avidin-biotin immunohistochemical technique using mouse monoclonal antibodies, and membranous, cytoplasmic and nuclear cellular localisation was assessed by light microscopy. Staining distribution scored as follows: 3, > 90 % positive epithelial cells; 2, >50 % positive epithelial cells; 1, <50 % positive epithelial cells. Non-dysplastic colonic epithelial cells revealed beta-catenin expression at the membrane (33/41 scored 3),areas of cytoplasmic expression (24/41 scored 1) and no nuclear staining. Dysplastic colonic epithelium revealed increased membranous and cytoplasmic, beta-catenin immunoreactivity (39/41 and 38/41 both scored 3) with focal nuclear staining (14/41). Expression patterns for ac-catenin, p120, and E-cadherin were similar to beta-catenin with increased membranous and cytoplasmic immunoreactivity in dysplastic mucosa, although no nuclear staining was observed. Increased cytoplasmic expression and nuclear localisation of beta-catenin are consistent with a possible mutation in its gene, and this finding was in keeping with the mutational analysis of exon 3 by single-strand conformational polymorphism. Increased immunoreactivity of the other catenins also suggests further disruption in catenin regulation. In summary, alterations in the beta-catenin expression and cellular localisation in the DMH-induced tumours are similar to those seen inhuman sporadic colorectal tumours. The DMH is therefore a useful model for studying the abnormalities of the E-cadherin-catenin pathway in colorectal carcinogenesis.