A new understanding of clinical patterns in post-TB lung disease.

Post-TB lung disease (PTLD) can be categorised based on physiological, radiological, and clinical abnormalities, delineating distinct clinical patterns; however, thus far the importance of this is unknown. People with PTLD have a high morbidity and increased mortality, but predictors of long-term outcomes are poorly understood.We conducted an observational study of PTLD patients attending a tertiary hospital in South Africa between 1 October 2021 and 30 September 2022. Patient demographics, risk factors, symptoms, lung function tests and outcomes were captured.A total of 185 patients were included (mean age: 45.2 years, SD ±14.3). Half of patients reported only one previous episode of Mycobacterium tuberculosis infection (n = 94, 50.8%). There was a statistically significant association between TB-associated obstructive lung disease (OLD) and dyspnoea (P = 0.002), chest pain (P = 0.014) and smoking (P = 0.005). There were significant associations between haemoptysis and both cavitation (P = 0.015) and fungal-associated disease (P < 0.001). Six patients (3.2%) died by study end.PTLD can affect young people even with only one previous episode of TB, and carries a high mortality rate. For the first time, clinical patterns have been shown to have meaningful differences; TB-related OLD is associated with dyspnoea, chest pain and smoking; while haemoptysis is associated with cavitary and fungal-associated disease..

Synovial fluid leukocyte cell count before versus after administration of antibiotics in patients with septic arthritis of a native joint.

BACKGROUND: Antibiotics have been shown to affect the accuracy of cultures; so antibiotics are held prior to obtaining cultures intra-operatively. No study has evaluated the effects of antibiotics on synovial fluid leukocyte cell count. The purpose of the current study is to compare the leukocyte cell count of native joints with septic arthritis when antibiotics have been given before aspiration and when no antibiotics have been given prior to aspiration. METHODS: This study was performed at a community hospital and a level 1 urban trauma hospital after IRB approval from both institutions from July 2007 to July 2017. Inclusion criteria comprised of a diagnosis of septic arthritis with positive cultures and a recorded arthrocentesis with cell count performed. Patients with septic arthritis were identified using ICD-9 codes 711.00-711.99 and ICD-10 codes M00 - M02. A retrospective chart review was performed and data was collected. Patients were placed into one of two groups. Group 1 received no antibiotics for two weeks prior to arthrocentesis, group 2 received antibiotics within 24 h prior to arthrocentesis. Demographic information, cell count number and differential, and blood lab values were collected. Timing data was also collected on timing of admission, antibiotics, joint irrigation, and discharge from the inpatient setting. RESULTS: There were 81 patients meeting final inclusion criteria. The average cell count for the group which received antibiotics (n = 30) was 40,408 ± 29,433 while the average cell count for the group receiving no antibiotics (n = 51) was 93,824 ± 73,875 (p < .0001). The average length of stay was not significantly different between the antibiotic group versus no antibiotic group (14.0 days vs 12.1 days p = .4). The time from admission to arthrocentesis and admission to washout was longer for the antibiotic group versus no antibiotic group (p = .004 and p = .002, respectively). CONCLUSION: When antibiotics are given prior to arthrocentesis of a septic joint, there is an associated lower synovial fluid leukocyte count compared to when no antibiotics are given prior. LEVEL OF EVIDENCE: Level III.

Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned.

BACKGROUND: Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here we outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance. METHODS: From 2016 PCV13 was introduced in a phased manner into the routine immunisation programme with some catch-up by the Government of Mongolia. We designed an evaluation to measure vaccine impact in children aged 2-59 months with hospitalised radiological pneumonia as a primary outcome, with secondary objectives to measure impact on clinically-defined pneumonia, nasopharyngeal carriage of S. pneumoniae among pneumonia patients and in the community, and severe respiratory infection associated with RSV and/or influenza. We enhanced an existing hospital-based pneumonia surveillance system by incorporating additional study components (nasopharyngeal swabbing using standard methods, C-reactive protein, risk factor assessment) and strengthening clinical practices, such as radiology as well as monitoring and training. We conducted cross-sectional community carriage surveys to provide data on impact on carriage among healthy children. DISCUSSION: Establishing a robust surveillance system is an important component of monitoring the impact of PCV within a country. The enhanced surveillance system in Mongolia will facilitate assessment of PCV13 impact on pneumonia, with radiological confirmed disease as the primary outcome. Key lessons arising from this evaluation have included the importance of establishing a core group of in-country staff to be responsible for surveillance activities and to work closely with this team; to be aware of external factors that could potentially influence disease burden estimates; to be flexible in data collection processes to respond to changing circumstances and lastly to ensure a consistent application of the pneumonia surveillance case definition throughout the study period.

Lack of evidence on mental health and well-being impacts of individual-level interventions for vulnerable adolescents: systematic mapping review.

OBJECTIVES: To review empirical evaluations of individual-level interventions intended to improve mental health or well-being for vulnerable adolescents. STUDY DESIGN: This is a systematic mapping review. METHODS: Thirteen databases covering academic and gray literature were searched for published reviews and randomised controlled trials, and gray literature (2005-2016) and the results quality-assessed to prioritise best available evidence. We aimed to identify well-conducted systematic reviews and trials that evaluated individual-level interventions, for mental health/well-being outcomes, where the population was adolescents aged 10-24 years in any of 12 vulnerable groups at high risk of poor health outcomes (e.g. homeless, offenders, 'looked after', carers). RESULTS: Thirty systematic reviews and 16 additional trials were identified. There was insufficient evidence to identify promising individual-level interventions that improve the mental health/well-being of any of the vulnerable groups. CONCLUSIONS: Despite Western policy to promote health and well-being among vulnerable young people, the dearth of evidence suggests a lack of interest in evaluating interventions targeting these groups in respect of their mental health/well-being outcomes.

Downstream consequences of diagnostic error in pediatric anaphylaxis.

BACKGROUND: Pediatric anaphylaxis is commonly misdiagnosed in the Emergency Department (ED). We aimed to determine the impact of inaccurate diagnosis on the management and follow-up of pediatric anaphylaxis presenting to the ED. METHODS: Retrospective chart review of ED management of children aged 0-18 years with allergic presentations to three EDs in Melbourne, Australia in 2014. Cases were included if an ED diagnosis of anaphylaxis was recorded, or the presentation met international consensus criteria for anaphylaxis. RESULTS: Of the 60,143 pediatric ED presentations during the study period, 1551 allergy-related presentations were identified and reviewed. 187 met consensus criteria for anaphylaxis, and another 24 were diagnosed with anaphylaxis without meeting criteria. Of the 211 presentations, 105 cases were given an ED diagnosis of anaphylaxis and 106 cases were given an alternative diagnosis in ED. Those diagnosed with anaphylaxis were more likely to receive epinephrine [85.7% vs 31.1% (OR = 13.27, 95% CI: 6.09-26.3)], to be observed for the recommended four hours [56.2% vs 29.2% (OR = 3.10, 95% CI 1.76-5.48, p < 0.001)], to have an epinephrine autoinjector available on discharge [81.9% vs 35.8% (OR = 4.12, 95% CI 2.07-8.22, p < 0.001)] and to be referred to an allergist [35.2% vs 16.0% (OR = 2.85, 95% CI 1.48-5.49, p < 0.01)]. Provision of anaphylaxis action plans and allergen avoidance advice was poorly documented for all patients. CONCLUSION: Accurate diagnosis of anaphylaxis in ED has a significant impact on observation times, prescription of epinephrine autoinjectors and referral to an allergist. These factors are key to reducing mortality and the significant morbidity that results from childhood anaphylaxis.

Retinal pigment epithelium transplantation: concepts, challenges, and future prospects.

The retinal pigment epithelium (RPE) is a single layer of cells that supports the light-sensitive photoreceptor cells that are essential for retinal function. Age-related macular degeneration (AMD) is a leading cause of visual impairment, and the primary pathogenic mechanism is thought to arise in the RPE layer. RPE cell structure and function are well understood, the cells are readily sustainable in laboratory culture and, unlike other cell types within the retina, RPE cells do not require synaptic connections to perform their role. These factors, together with the relative ease of outer retinal imaging, make RPE cells an attractive target for cell transplantation compared with other cell types in the retina or central nervous system. Seminal experiments in rats with an inherited RPE dystrophy have demonstrated that RPE transplantation can prevent photoreceptor loss and maintain visual function. This review provides an update on the progress made so far on RPE transplantation in human eyes, outlines potential sources of donor cells, and describes the technical and surgical challenges faced by the transplanting surgeon. Recent advances in the understanding of pluripotent stem cells, combined with novel surgical instrumentation, hold considerable promise, and support the concept of RPE transplantation as a regenerative strategy in AMD.

Phase III development of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire module for women undergoing breast reconstruction.

BACKGROUND: Comprehensive outcome assessments after breast reconstruction (BRR) require surgery-specific patient-reported outcome measures. The aims of this study were to assess the relevance, acceptability and redundancy of questions/items (phase III pretesting) of a new BRR questionnaire evaluating patients' health-related quality of life before and after BRR. Phase III occurred in collaboration with the European Organization for Research and Treatment of Cancer (EORTC) following earlier development phases that identified 31 items. METHODS: The EORTC BRR subgroup applied decision-making rules to each question according to eight EORTC criteria. A total of 197 patients (from the UK, Austria, Belgium, Italy and Sweden) were recruited. Forty-seven patients completed pre- and post-BRR questionnaires prospectively, and 150 reported post-BRR questionnaires only retrospectively. Qualitative debriefing interviews were undertaken in 189 patients. Preliminary psychometric analyses were performed. RESULTS: Thirty-one items fulfilled 'relevance', with none producing 'difficulties'. Ten items were not a priority for 10 per cent of respondents. Of these, two questions concerning muscle twitching in the affected breast and problem with donor-site swelling were deleted. Three redundant items were deleted: weakness in arm, which correlated significantly to the Quality of Life Questionnaire (QLQ) BR23 breast questionnaire, and shape and colour of the affected nipple. Descriptive statistics reduced the module to 26 items conceptualized into three provisional scales (disease treatment/surgery-related symptoms, sexuality and cosmetic outcome) within the newly completed questionnaire, EORTC QLQ-BRR26. CONCLUSION: The QLQ-BRR26 is available for psychometric validation in a large-field international sample. The intended use for QLQ-BRR26 is alongside EORTC QLQ-C30 and QLQ-BR23, in women treated by mastectomy for breast cancer and undergoing all types of BRR.

Aptamer BAX 499 mediates inhibition of tissue factor pathway inhibitor via interaction with multiple domains of the protein.

BACKGROUND: Tissue factor pathway inhibitor (TFPI) is a multidomain protein that negatively regulates the coagulation cascade. TFPI inhibits the tissue factor (TF)-activated factor VII-activated FX (FXa) complex during TF-mediated coagulation initiation. The aptamer BAX 499 binds specifically to TFPI and inhibits its function, mediating a procoagulant effect in both in vitro and in vivo models of hemophilia. OBJECTIVES: This study sought to identify the regions of TFPI that are critical for BAX 499 binding, and to determine how binding mediates aptamer inhibition of TFPI. METHODS AND RESULTS: In vitro biochemical methods were used to evaluate the BAX 499 interaction with and inhibition of TFPI. Binding experiments indicated that the full-length TFPI protein is required for tight aptamer binding. Binding-competition experiments implicated the Kunitz 1, Kunitz 3 and C-terminal domains of TFPI in aptamer binding, a finding that is supported by hydrogen-deuterium exchange experiments, and indicated that aptamer and FXa can bind simultaneously to TFPI. In enzymatic assays, BAX 499 inhibited TFPI in a manner that is distinct from domain-specific antibodies, and aptamer inhibitory activity is reduced in the presence of the TFPI cofactor protein S. CONCLUSIONS: These studies demonstrate that BAX 499 binds to TFPI via multiple domains of the protein in a manner that is distinct from other TFPI inhibitors, mediating a mechanism of inhibition that does not involve direct competition with FXa. With this unique inhibitory mechanism, BAX 499 provides a useful tool for studying TFPI biology in health and disease.

The early development phases of a European Organisation for Research and Treatment of Cancer (EORTC) module to assess patient reported outcomes (PROs) in women undergoing breast reconstruction.

INTRODUCTION: A comprehensive evaluation of breast reconstruction (BRR) surgery includes measurement of patient reported outcomes (PROs). There is, however, a lack of validated BRR-specific PRO measures (PROMs) that adequately assess relevant issues. This study is developing a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire/module specific for PROs in BRR to supplement the cancer-core and breast cancer EORTC questionnaires, respectively: the QLQ-C30 and QLQ-BR23. METHODS: Phases I and II of questionnaire development followed EORTC guidelines including a systematic literature review to identify all potential 'issues' (concepts relevant to PROs) and semi-structured interviews with 89 patients and 9 European multi-disciplinary health care professionals (HCPs) (Sweden, Italy and the United Kingdom [UK]). Interviewers asked participants the 'relevance' of outcomes identified in the literature and captured additional 'issues' of importance. RESULTS: The literature search and interviews of patients and HCPs yielded 69 issues relating to BRR operationalised into 31 provisional items (single questions) for the module, which was conceptualised to contain five scales: treatment/surgery related symptoms (affecting the shoulder, arm and reconstructed breast), body image, sexuality, cosmetic outcomes (pertaining to three areas: breast, donor site and nipple) and overall satisfaction. DISCUSSION: The provisional development of the EORTC BRR module has 31 items addressing issues of importance to patients as well as HCPs. Further international testing is underway as a UK National Cancer Research Network trial to ensure that this PROM will be psychometrically and clinically robust and applicable for use in clinical trials, cohort studies, national audit and clinical practice.

Traumatic tympanic membrane perforation by a needlefish: case report.

OBJECTIVES: We report a unique case of traumatic tympanic membrane perforation caused by a needlefish beak. We describe the mechanism of injury, the clinical findings and the treatment. CASE REPORT: An 11-year-old boy presented with otorrhoea and hearing loss secondary to a traumatic tympanic membrane perforation by a needlefish. The perforation was repaired by performing a myringoplasty, with satisfactory post-operative audiological results. CONCLUSION: To our knowledge, this is the first reported case of its kind. It is recommended that careful examination of the middle-ear space should always be carried out prior to and during myringoplasty if there is a possibility of a foreign body.

Parenting interventions for male young offenders: a review of the evidence on what works.

Approximately one in four incarcerated male young offenders in the UK is an actual or expectant father. This paper reviews evidence on the effectiveness of parenting interventions for male young offenders. We conducted systematic searches across 20 databases and consulted experts. Twelve relevant evaluations were identified: 10 from the UK, of programmes for incarcerated young offenders, and two from the US, of programmes for young parolees. None used experimental methods or included a comparison group. They suggest that participants like the courses, find them useful, and the interventions may improve knowledge about, and attitudes to, parenting. Future interventions should incorporate elements of promising parenting interventions with young fathers in the community, for example, and/or with older incarcerated parents. Young offender fathers have specific developmental, rehabilitative, and contextual needs. Future evaluations should collect longer-term behavioural parent and child outcome data and should use comparison groups and, ideally, randomization.

Large artery biomechanics and diastolic dysfunctionin patients with Type 2 diabetes.

AIMS: To comprehensively characterize large artery biomechanical properties and examine their relationship to cardiac function in patients with Type 2 diabetes mellitus (DM). METHODS: Fifty-five individuals with Type 2 DM were compared with 66 age- and sex-matched healthy control subjects. Arterial biomechanical properties were assessed by systemic arterial compliance (SAC; two-element Windkessel model), carotid-femoral pulse wave velocity (PWVc-f), femoral-dorsalis pedis pulse wave velocity (PWVf-d) and carotid augmentation index. Cardiac structure and function were assessed by echocardiography. RESULTS: Individuals with Type 2 DM had lower SAC and higher PWVc-f when compared with the healthy population. The PWVc-f was significantly lower than the PWVf-d in control individuals, but this difference was not evident in individuals with Type 2 DM due to higher PWVc-f. Augmentation index was similar in both groups, but the time to the first systolic inflection (time to reflection) was shorter in the individuals with Type 2 DM. The individuals with Type 2 DM had a greater prevalence of diastolic abnormalities when compared with the control group. Arterial stiffness indices, including SAC and pulse pressure, correlated with left ventricular filling pressure (defined as peak velocity during early diastolic filling divided by the velocity of movement of the mitral valve annulus in early diastole; r = -0.33 and 0.36 respectively. CONCLUSIONS: Patients with Type 2 DM on standard medication showed preferential stiffening of the large central arteries. However, carotid augmentation index was not different between the two groups and is therefore not a reliable indicator of large artery stiffening in this patient group. Diastolic dysfunction, present in a significant proportion of this population with Type 2 DM, was closely associated with arterial stiffening, suggesting a common aetiology.

Biodegradable poly(α-hydroxy ester) blended microspheres as suitable carriers for retinal pigment epithelium cell transplantation.

Five blends of poly(L-lactic acid) (PLLA) with poly(D,L-lactic-co-glycolic acid) (PLGA) were used to prepare microcarriers by a solvent evaporation technique. Microcarriers were evaluated as suitable scaffolds to facilitate retinal pigment epithelium (RPE) cell transplantation. The blend ratios were 90:10, 75:25, 50:50, 25:75, 10:90 (PLLA:PLGA). Samples of each microcarrier blend were coated with an extracellular matrix protein. Coated and uncoated microcarriers were seeded with a human RPE cell line. As the lactide unit content increased the size of microcarriers generally became larger and the surface more irregular. Cells remained proliferative and retained phenotype as confirmed by immunocytochemistry. Blends rich in PLLA were superior for maintenance of RPE cell viability. This study demonstrates for the first time the feasibility of using microcarriers as a vehicle for retinal cell transplantation for ocular disease.

Smoke-free homes: an intervention to reduce second-hand smoke exposure in households.

BACKGROUND: Second-hand tobacco smoke is a serious health hazard. We tested the fidelity and feasibility of the Smoke-Free Homes (SFH) intervention and looked for preliminary evidence of its effectiveness in imposing smoking restrictions in homes in Pakistan. METHODS: SFH was piloted and adapted for Pakistan. The adapted SFH intervention was then delivered to primary schoolchildren, community leaders and health professionals in a semi-rural Union Council. We carried out a survey before and after the intervention to assess adult smoking behaviour and restrictions at homes. We also carried out focus group discussions with stakeholders to determine the appropriateness and acceptability of the intervention. RESULTS: We found the adapted SFH intervention feasible and appropriate in a typical semi-rural setting in Pakistan. The proportion of smoke-free homes increased from 43% (95%CI 37.4-48.2) to 85% (95%CI 80.9-89.2) after the intervention. The number of households with at least one smoker decreased from 57.5% (95%CI 52.1-62.9) to 38.4% (95%CI 32.7-44.1). There was a reduction in self-reported adult smoking prevalence from 44% (95%CI 39-48) to 28% (95%CI 24-33) in males. CONCLUSION: SFH has the potential to influence adult smoking behaviour in households. This approach needs to be further evaluated to establish its effectiveness and cost-effectiveness and to ascertain its long-term sustainability.

Health-related quality of life assessment after breast reconstruction.

BACKGROUND: Health-related quality of life (HRQL) is an important outcome following breast reconstruction. This study evaluated current methods of HRQL assessment in patients undergoing latissimus dorsi breast reconstruction, hypothesizing that early surgical morbidity would be reflected by poorer HRQL scores. METHODS: Patients completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 and breast module (QLQ-BR23), the Functional Assessment of Cancer Therapy (FACT) general measure, and breast module and arm subscale (FACT-B + 4), and the Body Image Scale and Hospital Anxiety and Depression Scale (HADS) 3 months after surgery. They also reported additional HRQL problems not included in the questionnaires. HRQL scores were compared between patients with and without early surgical morbidity. RESULTS: Sixty women completed the questionnaires, of whom 25 (42 per cent) experienced complications. All EORTC and FACT subscale and HADS scores were similar in patients with or without morbidity. Women with complications were twice as likely to report feeling less feminine and dissatisfied with the appearance of their scar than those without problems. Thirty-two women (53 per cent) complained of problems not covered by the questionnaires, most commonly donor-site morbidity. CONCLUSION: Existing HRQL instruments are not sufficiently sensitive to detect clinically relevant problems following breast reconstruction.

Bone cement implantation syndrome.

Bone cement implantation syndrome (BCIS) is poorly understood. It is an important cause of intraoperative mortality and morbidity in patients undergoing cemented hip arthroplasty and may also be seen in the postoperative period in a milder form causing hypoxia and confusion. Hip arthroplasty is becoming more common in an ageing population. The older patient may have co-existing pathologies which can increase the likelihood of developing BCIS. This article reviews the definition, incidence, clinical features, risk factors, aetiology, pathophysiology, risk reduction, and management of BCIS. It is possible to identify high risk groups of patients in which avoidable morbidity and mortality may be minimized by surgical selection for uncemented arthroplasty. Invasive anaesthetic monitoring should be considered during cemented arthroplasty in high risk patients.

A dose of realism for healthy urban policy: lessons from area-based initiatives in the UK.

Many urban policies aim to improve areas and address socioeconomic deprivation. The resulting investment is often delivered through area-based programmes which incorporate initiatives to improve the physical, social and economic environment. Hypotheses that these investments can contribute to wider public health strategies are based on epidemiological data and used to support the concept of healthy urban policy. However, there is little evidence on their ability to generate positive impacts on socioeconomic or health outcomes. The lack of validating evidence on actual impacts raises two important questions: (1) Is area-based investment an effective strategy to tackle socioeconomic deprivation? (2) What is the prospect for new and improved evaluations to provide stronger evidence? Both the programmes of area investment and their accompanying evaluations have been criticised for being overly ambitious in what can be achieved by the investment and what can be measured by an evaluation. Area-based approaches to tackling deprivation have their advantages but a mix of area and individual-level targeting is likely to be needed. While there is scope to improve the utility of evaluation data there are also inevitable constraints on assessing and attributing impacts from urban investment. The inherent limitations to an area-based approach and the ongoing constraints on impact evaluation will inevitably temper expectations of what healthy urban policy can achieve. However, lack of evidence is not grounds to abandon the concept of healthy urban policy; adoption of more realistic expectations together with improved evaluation data may help to increase its credibility.