Scale-up of the Internet-based Professional Learning to help teachers promote Activity in Youth (iPLAY) intervention: a hybrid type 3 implementation-effectiveness trial.

BACKGROUND: Whole-of-school programs have demonstrated success in improving student physical activity levels, but few have progressed beyond efficacy testing to implementation at-scale. The purpose of our study was to evaluate the scale-up of the 'Internet-based Professional Learning to help teachers promote Activity in Youth' (iPLAY) intervention in primary schools using the RE-AIM framework. METHODS: We conducted a type 3 hybrid implementation-effectiveness study and collected data between April 2016 and June 2021, in New South Wales (NSW), Australia. RE-AIM was operationalised as: (i) Reach: Number and representativeness of students exposed to iPLAY; (ii) Effectiveness: Impact of iPLAY in a sub-sample of students (n = 5,959); (iii) Adoption: Number and representativeness of schools that received iPLAY; (iv) Implementation: Extent to which the three curricular and three non-curricular components of iPLAY were delivered as intended; (v) Maintenance: Extent to which iPLAY was sustained in schools. We conducted 43 semi-structured interviews with teachers (n = 14), leaders (n = 19), and principals (n = 10) from 18 schools (11 from urban and 7 from rural locations) to determine program maintenance. RESULTS: Reach: iPLAY reached ~ 31,000 students from a variety of socio-economic strata (35% of students were in the bottom quartile, almost half in the middle two quartiles, and 20% in the top quartile). EFFECTIVENESS: We observed small positive intervention effects for enjoyment of PE/sport (0.12 units, 95% CI: 0.05 to 0.20, d = 0.17), perceptions of need support from teachers (0.26 units, 95% CI: 0.16 to 0.53, d = 0.40), physical activity participation (0.28 units, 95% CI: 0.10 to 0.47, d = 0.14), and subjective well-being (0.82 units, 95% CI: 0.32 to 1.32, d = 0.12) at 24-months. Adoption: 115 schools received iPLAY. IMPLEMENTATION: Most schools implemented the curricular (59%) and non-curricular (55%) strategies as intended. Maintenance: Based on our qualitative data, changes in teacher practices and school culture resulting from iPLAY were sustained. CONCLUSIONS: iPLAY had extensive reach and adoption in NSW primary schools. Most of the schools implemented iPLAY as intended and effectiveness data suggest the positive effects observed in our cluster RCT were sustained when the intervention was delivered at-scale. TRIAL REGISTRATION: ACTRN12621001132831.

Detection of Pneumocystis jirovecii by quantitative real-time PCR in oral rinses from Pneumocystis pneumonia asymptomatic human immunodeficiency virus patients.

Pneumocystis pneumonia (PCP) is a potentially life-threatening fungal infection usually seen in immunocompromised patients. Pneumocystis jirovecii can be easily detected from oral rinse samples in HIV patients with suspected PCP. In this study, a quantitative real-time PCR assay was used to establish the frequency of detection of P. jirovecii in oral rinses from HIV patients without respiratory symptoms or suspicion of PCP. Two saline oral rinses were collected from 100 ambulant HIV patients and from 60 COPD patients (comparator group). Four HIV patients were positive for P. jirovecii. In three patients, the first sample was positive and in one the second one was positive. One of these patients was on PCP prophylaxis and had a CD4+ count of 76 cells/mm3. The mean CD4+ count for all patients was 527 cells/mm3. All qRT-PCR test results for the COPD patients were negative. No patient developed PCP at six months follow-up. The qRT-PCR assay can be used to detect P. jirovecii DNA in oral rinse samples from HIV patients without evident clinical symptoms, however the oral carriage of this fungus was rare in our cohort of patients. In conclusion, although rare, a positive oral rinse P. jirovecii result may reflect colonisation, in particular in patients with HIV. This needs to be kept in mind when using oral rinses and qRT-PCR in the diagnosis of P. jirovecii infection.

Targeted lung cancer screening selects individuals at high risk of cardiovascular disease.

BACKGROUND: Cardiovascular disease (CVD) is a major cause of morbidity and mortality in populations eligible for lung cancer screening. The aim of this study was to determine whether a brief CV risk assessment, delivered as part of a targeted community-based lung cancer screening programme, was effective in identifying individuals at high risk who might benefit from primary prevention. METHODS: The Manchester Lung Screening Pilot consisted of annual low dose CT (LDCT) over 2 screening rounds, targeted at individuals in deprived areas at high risk of lung cancer (age 55-74 and 6-year risk ≥1.51%, using PLCOM2012 risk model). All participants of the second screening round were eligible to take part in the study. Ten-year CV risk was estimated using QRISK2 in participants without CVD and compared to age (±5 years) and sex matched Health Survey for England (HSE) controls; high risk was defined as QRISK2 score ≥10%. Coronary artery calcification (CAC) was assessed on LDCT scans and compared to QRISK2 score. RESULTS: Seventy-seven percent (n=920/1,194) of screening attendees were included in the analysis; mean age 65.6 ± 5.4 and 50.4% female. QRISK2 and lung cancer risk (PLCOM2012) scores were correlated (r = 0.26, p < 0.001). Median QRISK2 score was 21.1% (IQR 14.9-29.6) in those without established CVD (77.6%, n = 714/920), double that of HSE controls (10.3%, IQR 6.6-16.2; n = 714) (p < 0.001). QRISK2 score was significantly higher in those with CAC (p < 0.001). Screening attendees were 10-fold more likely to be classified high risk (OR 10.2 [95% CI 7.3-14.0]). One third (33.7%, n = 310/920) of all study participants were high risk but not receiving statin therapy for primary CVD prevention. DISCUSSION: Opportunistic CVD risk assessment within a targeted lung cancer screening programme is feasible and is likely to identify a very large number of individuals suitable for primary prevention.

Telomere length measurement can distinguish pathogenic from non-pathogenic variants in the shelterin component, TIN2.

Dyskeratosis congenita (DC) is a heterogeneous bone marrow failure syndrome with seven disease-causing genes identified to date, six of which are linked to telomere maintenance. Mutations in one of these genes (TINF2), which encodes a component of the shelterin complex, are associated with particularly short telomeres. Among the 224 consecutive patients with different forms of bone marrow failure (46 with DC, 122 with aplastic anaemia and 57 with some features of DC), we have identified 16 new families with variants in exon 6 of the TINF2 gene, eight of which are novel. We observe that the phenotype associated with these mutations extends to a severe early presentation, not always classified as DC. In addition, we see that some of the variants identified are not associated with short telomeres and are also found in asymptomatic individuals. In the absence of any direct functional assay, the data indicates that the telomere length measurement can inform us as to which variants in TINF2 are pathogenic and which may be non-pathogenic.

Dyskeratosis congenita: a genetic disorder of many faces.

Dyskeratosis congenita (DC) is an inherited syndrome exhibiting marked clinical and genetic heterogeneity. It is characterized by multiple features including mucocutaneous abnormalities, bone marrow failure and an increased predisposition to cancer. Three genetic subtypes are recognized: X-linked recessive DC bears mutations in DKC1, the gene encoding dyskerin, a component of H/ACA small nucleolar ribonucleoprotein particles; autosomal dominant (AD) DC has heterozygous mutations in either TERC or TERT, the RNA and enzymatic components of telomerase, respectively, and autosomal recessive DC in which the genes involved remain largely elusive. Disease pathology is believed to be a consequence of chromosome instability because of telomerase deficiency due to mutations in DKC1, TERC and TERT; in patients with DKC1 mutations, defects in ribosomal RNA modification, ribosome biogenesis, translation control or mRNA splicing may also contribute to disease pathogenesis. The involvement of telomerase complex components in X-linked and AD forms and the presence of short telomeres in DC patients suggest that DC is primarily a disease of defective telomere maintenance. Treatment is variable and complicated by the development of secondary cancers but, being a monogenic disorder, it could potentially be treated by gene therapy. DC overlaps both clinically and genetically with several other diseases including Hoyeraal-Hreidarsson syndrome, aplastic anaemia and myelodysplasia, among others and its underlying telomeric defect has implications for a broader range of biological processes including ageing and many forms of cancer.

Pharmacokinetics of sirolimus in heart transplant recipients with chronic renal impairment.

BACKGROUND: A common clinical problem following organ transplantation is the development of renal failure due to calcineurin inhibitors. Sirolimus offers the potential of providing appropriate immunosuppression without nephrotoxicity. This study evaluates the impact of sirolimus monotherapy on renal function in patients late following heart transplantation and correlates trough sirolimus levels with area-under-the-concentration time curve measurements. METHODS: Six male patients with renal impairment late following heart transplantation (mean 8 years) were offered sirolimus therapy. Calcineurin inhibition was discontinued in all patients on commencing sirolimus. Patients started on sirolimus 2 to 5 mg/d orally. Venous blood samples for pharmacokinetic studies and repeat creatinine clearance were performed before and 6 weeks after commencement of sirolimus in all subjects. RESULTS: Sirolimus trough levels accurately reflected sirolimus area-under-the-concentration time curve measurements. There was no change in renal function. Mean creatinine clearance prior to commencing sirolimus was 26.7 (12.2) mL/min and the post-sirolimus creatinine clearance performed 6 weeks later was 23.4 (11.7) mL/min (P = .64). CONCLUSIONS: Trough levels of sirolimus correlate with drug exposure and may be used to monitor sirolimus therapy. No improvement in renal function following calcineurin inhibitor withdrawal occurred in this cohort.

Uptake of screening for breast cancer in south Lancashire.

STUDY OBJECTIVE: To describe and explain variation among general practices in the uptake of screening for breast cancer. DESIGN: Analysis of the variation in uptake of screening by general practice. Uptake rates are calculated and related to a social deprivation score created for each practice, and to the presence of at least one female general practitioner. SETTING: South Lancashire Health Authority, England. PATIENTS: All women aged 50-64 y registered with Lancashire Family Health Services Authority and resident in South Lancashire in 1988-1995. MAIN RESULTS: Variation in the uptake of screening for breast cancer during Round 1 of the national programme is explained partly by a deprivation score for each practice and by the presence of at least one female general practitioner. In Round 2 the deprivation index continues to explain variation, but the effect of a female GP has diminished. The number of hours worked by practice nurses has no effect on uptake of breast screening. CONCLUSIONS: Variation in the uptake of breast cancer screening is closely related to social deprivation. Results suggest that the presence of a female general practitioner has a beneficial effect on uptake.

Investigation of burnout in a sample of British general practitioners.

BACKGROUND: Recent changes in the general practitioner contract have produced increased workload and stress, poorer mental health and reduced job satisfaction. These factors might combine to increase the level of 'burnout' among general practitioners. AIM: This study set out to examine the extent of burnout among general practitioners. METHOD: A questionnaire was sent to all 295 Northamptonshire general practitioners seeking demographic details and including the Maslach burnout inventory. The results for the inventory were compared with the results from a sample of physicians and nurses in North America. RESULTS: There was a significantly higher level of burnout among the Northamptonshire doctors compared with the North American sample. There was virtually no association between age and the level of burnout, although a small negative correlation was found between age and the depersonalization of others subscale. Part-time general practitioners showed lower levels of burnout than full-time general practitioners. CONCLUSION: This study highlights the need to look both at the extent of burnout in young doctors during their training and at those characteristics of part-time general practitioners which might prevent burnout.