Investigating the spatial and temporal variation of vape retailer provision in New Zealand: A cross-sectional and nationwide study.

Smoking rates have decreased in Aotearoa New Zealand in recent years however, vaping has shown a dramatic upward trend especially among young people; up to 10% of young New Zealanders are now regular vapers. Importantly, the long-term health consequences for their future life are largely unknown. The accessibility of vape retailers is important, particularly in relation to the youths' daily activities and places such as schools where they spend a considerable amount of time and socialise. Despite this, we know little about the spatial patterning of vape retailers and even less of their socio-spatial patterning around schools. This ecological study utilised data from the New Zealand Specialist Vape Retailers register on nationwide vape retailer locations and combined them with whole-population sociodemographic characteristics and primary and secondary school data. We identified the prevalence of vape retailers and their spatial distribution by area-level deprivation, ethnicity and urban-rural classification by using descriptive statistics and (spatial) statistical modelling on the area-, school- and individual students-level (using disaggregated data on students). We found that almost 97% of all vape retailers are located within 1,600m (∼20-min walk) and 29% within 400m (∼5-min walk) of schools. Our research also identified increasing inequities by deprivation and ethnicity both for the overall population and particularly for students in the most deprived areas who experience a disproportionate presence and increase of new vape store retailers that disadvantage schools and students in these areas. This difference was particularly prominent for Pasifika populations in major urban environments.

Health-promoting and health-constraining environmental features and physical activity and sedentary behaviour in adolescence: a geospatial cross-sectional study.

The environment may be an important influence on adolescent behaviour. We combined accelerometry and global positioning system data to investigate how the environment was related to physical activity and sedentary behaviour. Adolescents spent most of their time in very close proximity to a range of both health-promoting and health-constraining features. Several associations were detected between time spent in areas with the greatest access to health-promoting features and reduced sedentary time and less travel time by motor vehicle. The environment may contribute to the variation in adolescent activity behaviour.

The environment an adult resides within is associated with their health behaviours, and their mental and physical health outcomes: a nationwide geospatial study.

BACKGROUND: The determinants of health behaviours and health outcomes are multifaceted and the surrounding environment is increasingly considered as an important influence. This pre-registered study investigated the associations between the geospatial environment people live within and their health behaviours as well as their mental and physical health outcomes. METHOD: We used the newly developed Healthy Location Index (HLI) to identify health-promoting and health-constraining environmental features where people live. We then used Time 10 (2018) data from the New Zealand Attitudes and Values Survey (NZAVS; N = 47,951), a national probability sample of New Zealand adults, to gauge mental health outcomes including depression, anxiety and psychological distress, physical health outcomes including BMI and type II diabetes, and health behaviours such as tobacco smoking and vaping. Linear and logistic multilevel mixed effect regression models with random intercepts of individuals nested within geographical areas (meshblocks) were employed. RESULTS: The presence of health-constraining environmental features were adversely associated with self-reported mental health outcomes of depression, anxiety and psychological distress, physical health outcomes of BMI and type II diabetes, and negative health behaviours of tobacco smoking and vaping. By contrast, health-promoting environmental features were uniquely associated only with physical health outcomes of BMI and type II diabetes. CONCLUSION: The current study advances research on environmental determinants of health behaviours by demonstrating that close proximity to health-constraining environmental features is related to a number of self-reported physical and mental health outcomes or behaviours. We provide some evidence to support the notion that preventive population-health interventions should be sought.

"Real-life" data of the efficacy and safety of belantamab mafodotin in relapsed multiple myeloma-the Mayo Clinic experience.

Belantamab mafodotin is a highly selective targeted therapy for multiple myeloma. It targets the B cell maturation antigen (BCMA) on plasma cells and showed promising results in several randomized clinical trials. We report the outcomes of 36 patients treated at Mayo Clinic. Our cohort received a median of eight prior lines of therapy. Six patients received belantamab in combination with other medications (pomalidomide, cyclophosphamide, thalidomide), 13 patients (36%) were 70 years or older, two patients had a creatinine of >2.5 mg/dL, and one patient was on dialysis. All three patients with renal failure received full dose belantamab. Chimeric antigen receptor (CAR-T) therapy was used prior to belantamab in seven patients and none of them responded to belantamab therapy. The overall response rate (ORR) was 33% (CR 6%, VGPR 8%, PR 19%), like the ORR reported in the DREAMM-2 trial. Keratopathy developed in 16 patients (43%), grade 1 in six patients, grade 2 in seven patients, and grade 3 in three patients. Eight percent discontinued therapy due to keratopathy. The median PFS and OS was 2 months and 6.5 months, respectively.

Close proximity to alcohol outlets is associated with increased crime and hazardous drinking: Pooled nationally representative data from New Zealand.

This nationwide study investigated the relationship between proximity to alcohol outlets (off-licence, on-licence, and other-licence) and two adverse outcomes; hazardous drinking and crime (common assault, non-aggravated sexual assault, aggravated sexual assault, and tobacco and liquor offences). After adjustment for important individual- and area-level factors, close proximity to alcohol outlets was associated with increased risk of hazardous drinking, with strong associations for on-licence outlets. Proximity alcohol outlets was also strongly associated with all crime outcomes, often with a dose-response relationship. Nationally representative New Zealand data showed that close proximity to alcohol outlets was associated with increased crime and hazardous drinking.

Investigating the relationship between multimorbidity and dental attendance: a cross-sectional study of UK adults.

Introduction: Regular dental attendance is related to better oral health. However, long-standing health conditions (LSHCs) may be related to dental attendance and this relationship may vary by socioeconomic status. Method: Data were collected from wave two (2013­2015) of the Yorkshire Health Study (n= 7,654). Data included dental attendance, LSHC, age, gender, education-level, smoking, body mass index, and area-level deprivation. Logistic regression (attend or not) was used to analyse associations with LSHC and multimorbidity. Results: Overall, 63.1% (n = 4,826) of individuals attended the dentist. Of these, 37.8% (n =2894) had no LSHC, 26.0% (n = 1987) had one LSHC and 36.4% (n = 2784) had two or more LSHC. The presence of a singular LSHC was not associated with dental attendance(OR = 0.91 [0.81, 1.04]), however, those with two or more LSHCs were more likely to attend the dentist (OR = 0.81 [95% CI 0.72, 0.92]). Interactions between individual-level education, as a marker of socioeconomic status, and LSHC revealed few associations with dental attendance. Conclusion: Multimorbidity was associated with dental attendance such that those with multimorbidity were more likely to attend. These important findings highlight the increasing challenge of multimorbidity for global healthcare systems.

Clusters of health behaviours in Queensland adults are associated with different socio-demographic characteristics.

BACKGROUND: The co-occurrence of unhealthy lifestyles, calls for interventions that target multiple health behaviours. This study investigates the clustering of health behaviours and examines demographic differences between each cluster. METHODS: In total, 934 adults from Queensland, Australia completed a cross-sectional survey assessing multiple health behaviours. A two-step hierarchical cluster analysis using multiple iterations identified the optimal number of clusters and the subset of distinguishing health behaviour variables. Univariate analyses of variance and chi-squared tests assessed difference in health behaviours by socio-demographic factors and clusters. RESULTS: Three clusters were identified: the 'lower risk' cluster (n = 436) reported the healthiest profile and met all public health guidelines. The 'elevated risk' cluster (n = 105) reported a range of unhealthy behaviours such as excessive alcohol consumption, sitting time, fast-food consumption, smoking, inactivity and a lack of fruit and vegetables. The 'moderate risk behaviour' cluster (n = 393) demonstrated some unhealthy behaviours with low physical activity levels and poor dietary outcomes. The 'elevated risk' cluster were significantly younger and more socio-economically disadvantaged than both the 'lower and moderate risk' clusters. DISCUSSION: Younger people who live in more deprived areas were largely within the 'elevated risk' cluster and represent an important population for MHBC interventions given their wide range of unhealthy behaviours.

Natural history of t(11;14) multiple myeloma.

Translocation (11;14) on interphase fluorescent in situ hybridization in plasma cells is regarded as a standard risk prognostic marker in multiple myeloma based on studies conducted before introduction of current therapies. We identified 365 patients with t(11;14), and 730 matched controls:132 patients with non-(11;14) translocations and 598 patients with no chromosomal translocation. The median progression-free survival for the three groups were 23.0 (95% confidence interval (CI), 20.8-27.6), 19.0 (95% CI, 15.8-22.7) and 28.3 (95% CI, 25.7-30.6) months, respectively (P<0.01). The median overall survival (OS) for t(11;14), non-(11;14) translocation and no-translocation groups were 74.4 (95% CI, 64.8-89.3), 49.8 (95% CI, 40.0-60.6) and 103.6 (95% CI, 85.2-112.3) months, respectively (P<0.01). Excluding those with 17p abnormality, the median OS in the three groups were 81.7 (95% CI, 67.0-90.7), 58.2 (95% CI, 47.0-76.4) and 108.3 (95% CI, 92.4-140.1) months, respectively (P<0.01). The above relationship held true in patients with age <65 years, international staging system (ISS) I/II stage or those who received novel agent-based induction. Advanced age (hazard ratio (HR): 1.98), 17p abnormality (HR: 2.2) and ISS III stage (HR: 1.59) at diagnosis predicted reduced OS in patients with t(11;14). These results suggest that outcomes of t(11;14) MM are inferior to other standard risk patients.

Clinical presentation and outcomes in light chain amyloidosis patients with non-evaluable serum free light chains.

Hematologic response criteria in light chain (AL) amyloidosis require the difference in involved and uninvolved free light chains (dFLC) to be at least 5 mg/dl. We describe the clinical presentation and outcomes of newly diagnosed amyloidosis patients with dFLC <5 mg/dl (non-evaluable dFLC; 14%, n=165) compared with patients with dFLC ⩾5 mg/dl (evaluable dFLC; 86%, n=975). Patients with non-evaluable dFLC had less cardiac involvement (40% vs 80%, P<0.001), less liver involvement (11% vs 17%, P=0.04) and a trend toward less gastrointestinal involvement (18% vs 25%, P=0.08). However, significantly higher renal involvement (72% vs 56%, P=0.0002) was observed in the non-evaluable dFLC cohort. Differences in treatment patterns were observed, with 51% of treated patients undergoing upfront stem cell transplantation in the non-evaluable cohort compared with 28% in the evaluable dFLC group (P<0.001). Progression-free survival (61 vs 13 months, P<0.001) and overall survival (OS; 101 vs 29 months, P<0.001) were significantly longer in the non-evaluable dFLC cohort. Normalization of involved light chain levels and decrease in dFLC <1 mg/dl (baseline at least 2 mg/dl) were predictive of OS and associated with better dialysis-free survival and may be used for response assessment in patients with non-evaluable FLC levels.

Clinical utility of the Revised International Staging System in unselected patients with newly diagnosed and relapsed multiple myeloma.

We analyzed the utility of Revised International staging system (RISS) in an unselected cohort of newly diagnosed multiple myeloma (NDMM; cohort 1), and relapsed/refractory multiple myeloma (RRMM; cohort 2) patients. Cohort 1 included 1900 patients seen within 90 days of diagnosis, from 2005 to 2015, while cohort 2 had 887 patients enrolled in 23 clinical trials at Mayo Clinic. The overall survival (OS) and progression-free survival (PFS) was calculated from the time since diagnosis or trial registration. The median estimated follow up was 5 and 2.3 years for Cohorts 1 and 2, respectively. Among 1067 patients evaluable in Cohort 1, the median OS and PFS was 10 and 2.8 years for RISS stage I, 6 and 2.7 years for RISS stage II and 2.6 and 1.3 years for RISS stage III (P<0.0001). Among 456 patients evaluable in Cohort 2, the median OS and PFS was 4.3 and 1.1 years for RISS stage I, 2 and 0.5 years for RISS stage II and 0.8 and 0.2 years for RISS stage III (P<0.0001). In conclusions, RISS gives a better differentiation of NDMM as well as RRMM patients into three survival subgroups and should be used to stratify patients in future clinical trials.

Using quality indicators to compare outcomes of permanent cardiac pacemaker implantation among publicly and privately funded patients.

BACKGROUND: Funding source/insurance status has been associated with disparity in the management and outcomes of cardiovascular disease, with poorer outcomes among disadvantaged groups. AIM: Using proposed quality indicators for permanent pacemaker (PPM) implantation and administrative data, this study aimed to determine whether quality indicator-based outcomes of PPM implantation were comparable for publicly and privately funded patients within Australia's two-tier health system. METHODS: A population-based cohort study of adults implanted with a PPM between 1995 and 2009 in Western Australia. The association of funding outcomes derived from linked administrative data was tested in multivariate logistic regression models. RESULTS: There were 9748 PPMs implanted, 48% being among privately funded patients. The mean age was 75 years for both public and private patients. Private patients had better health status (fewer with cardiac conditions and lower non-cardiac comorbidity scores), were less likely to be an emergency admission (33% vs 60%, P < 0.001) and more likely to have dual- or triple-chamber pacing. Mean length of stay was significantly greater for private patients (4.3 (standard deviation 6.3) vs 5.1 (6.8) days <0.001), related to longer elective admissions. Crude mortality was lower for private patients in-hospital (0.7 vs 1.3%), 30-day post-procedure (1.3 vs 2.1%) and at 1 year (7.3 vs 9.5%). Emergency admission, comorbidity and other demographic and clinical factors, not funding source, were significant predictors of these outcomes. CONCLUSIONS: There was no difference between publicly and privately funded patients in study outcomes, after adjustment for demographic and clinical factors. The exception was longer hospital stay for elective PPM among privately funded patients.

Evaluation of long-term clinical and health service outcomes following coronary artery revascularisation in Western Australia (WACARP): a population-based cohort study protocol.

INTRODUCTION: Coronary artery bypass grafting (CABG) and percutaneous coronary interventions (PCI) are procedures commonly performed on patients with significant obstructive coronary artery disease to relieve symptoms of ischaemia, improve survival or both. Although the efficacy of both procedures at the individual level has been established, the impact of advances in coronary artery revascularisation procedures (CARP) on long-term outcomes and cost-effectiveness at the population level are yet to be assessed. Our aim is to evaluate a minimum of 6-year outcomes and costs for the total population of patients who had CARP in Western Australia (WA) in 2000-2005. METHODS AND ANALYSIS: This retrospective population cohort study will link clinical and administrative health data for a previously defined cohort including all patients in WA who had a CARP in the period 2000-2005. The cohort consists of 19,014 patients who had 21,175 procedures (15,429 PCI and 5746 CABG). We are now collecting a minimum of 6 years follow-up of morbidity and mortality data for the cohort using the WA Data Linkage System, clinical registries and hospital records, with 12 years follow-up for cases in the year 2000. Comparison of long-term outcomes for different CARP will be reported (PCI vs CABG; bare metal stents vs drug-eluting stents vs CABG). Cost-effectiveness analysis of CARP from the perspective of the healthcare sector will be performed using individual level cost data and average costs from Australian Refined Diagnosis Related Groups. ETHICS AND DISSEMINATION: This study has received ethics approval from the University of Western Australia, the Western Australian Department of Health and all participating hospitals. Being a large population cohort study, approval included a waiver of informed consent. All findings will be presented at local, national and international healthcare/academic conferences and published in peer-reviewed journals.

Antimicrobial susceptibility and molecular typing of MRSA in cystic fibrosis.

OBJECTIVES: The prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in cystic fibrosis (CF) patients in the United States is approximately 25%. Little is known about the relative proportion of hospital- versus community-associated strains or the antimicrobial susceptibility of MRSA in different CF centers. We hypothesized that the majority of MRSA isolates obtained from children with CF are those endemic in the hospital and that those associated with community acquisition (SCCmec IV) would be more resistant than typically seen in non-CF MRSA isolates. METHODS: We studied MRSA strains from seven pediatric CF centers to determine the clonal distribution based on DNA sequencing of the staphylococcal protein A gene (spa typing), the type of staphylococcal chromosomal cassette mec (SCCmec), and the proportion of strains with Panton-Valentine leukocidin (PVL). Antimicrobial susceptibility to systemic and topical antibiotics was compared between different MRSA types. RESULTS: We analyzed 277 MRSA isolates from unique patients (mean age 11.15 ± 4.77 years, 55% male). Seventy % of isolates were SCCmec II PVL negative and the remainder SCCmec IV. Overall 17% MRSA strains were PVL positive (all SCCmec IV). Spa typing of 118 isolates showed most of the SCCmec II strains being t002, while SCCmec IV PVL positive isolates were t008, and SCCmec IV PVL negative isolates represented a variety of spa-types. The proportions of SCCmec II strains and spa-types were similar among centers. Overall rates of resistance to trimethoprim-sulfamethoxazole (4%), tetracycline (7%), tigecycline (0.4%), linezolid (0.4%) as well as fosfomycin (0.4%), fusidic acid (3%), and mupirocin (1%) were low. No strains were resistant to vancomycin. SCCmec II strains had higher rates of resistance to ciprofloxacin and clindamycin (P < 0.001) than SCCmec IV strains. CONCLUSIONS: In this U.S. study, most MRSA isolates in the pediatric CF population were SCCmec II PVL negative. Rates of resistance were low, including to older and orally available antibiotics such as trimethoprim-sulfamethoxazole.

SLCO1B1 genetic variant associated with statin-induced myopathy: a proof-of-concept study using the clinical practice research datalink.

This study aimed to determine whether patients with statin-induced myopathy could be identified using the United Kingdom Clinical Practice Research Datalink, whether DNA could be obtained, and whether previously reported associations of statin myopathy with the SLCO1B1 c.521T>C and COQ2 rs4693075 polymorphisms could be replicated. Seventy-seven statin-induced myopathy patients (serum creatine phosphokinase (CPK) > 4× upper limit of normal (ULN)) and 372 statin-tolerant controls were identified and recruited. Multiple logistic regression analysis showed the SLCO1B1 c.521T>C single-nucleotide polymorphism to be a significant risk factor (P = 0.009), with an odds ratio (OR) per variant allele of 2.06 (1.32-3.15) for all myopathy and 4.09 (2.06-8.16) for severe myopathy (CPK > 10× ULN, and/or rhabdomyolysis; n = 23). COQ2 rs4693075 was not associated with myopathy. Meta-analysis showed an association between c.521C>T and simvastatin-induced myopathy, although power for other statins was limited. Our data replicate the association of SLCO1B1 variants with statin-induced myopathy. Furthermore, we demonstrate how electronic medical records provide a time- and cost-efficient means of recruiting patients with severe adverse drug reactions for pharmacogenetic studies.

Mortality of former crocidolite (blue asbestos) miners and millers at Wittenoom.

BACKGROUND: Blue asbestos was mined and milled at Wittenoom in Western Australia between 1943 and 1966. METHODS: Nearly 7000 male workers who worked at the Wittenoom mine and mill have been followed up using death and cancer registries throughout Australia and Italy to the end of 2000. Person-years at risk were derived using two censoring dates in order to produce minimum and maximum estimates of asbestos effect. Standardised mortality ratios (SMRs) compare the mortality of the former Wittenoom workers with the Western Australian male population. RESULTS: There have been 190 cases of pleural and 32 cases of peritoneal mesothelioma in this cohort of former workers at Wittenoom. Mortality from lung cancer (SMR = 1.52), pneumoconiosis (SMR = 15.5), respiratory diseases (SMR = 1.58), tuberculosis (SMR = 3.06), digestive diseases (SMR = 1.47), alcoholism (SMR = 2.24) and symptoms, signs and ill defined conditions (SMR = 2.00) were greater in this cohort compared to the Western Australian male population. CONCLUSION: Asbestos related diseases, particularly malignant mesothelioma, lung cancer and pneumoconiosis, continue to be the main causes of excess mortality in the former blue asbestos miners and millers of Wittenoom.

Adenoviral-mediated PTEN expression radiosensitizes non-small cell lung cancer cells by suppressing DNA repair capacity.

Expression of the PTEN tumor suppressor gene is abnormal in many human cancers. Loss of PTEN expression leads to the activation of downstream signaling pathways that have been associated with resistance to radiation. In non-small cell lung carcinoma (NSCLC), suppressed expression of PTEN is frequently due to methylation of its promoter region. In this study, we tested whether gene transfer of wild-type PTEN into an NSCLC cell line with a known methylated PTEN promoter, H1299, would increase its sensitivity to ionizing radiation. Pretreating H1299 cells with an adenoviral-mediated PTEN (Ad-PTEN)-expressing vector sensitized H1299 cells to radiation. To determine the mechanism responsible for radiosensitization, we first examined radiation-induced apoptosis, which was enhanced but did not correlate with radiosensitizing effect of Ad-PTEN. Therefore, we next examined the ability of Ad-PTEN to modulate the repair of radiation-induced DNA double-strand breaks (DSBs) using the detection of repair foci positive for gamma-H2AX, a protein that becomes evident at the sites of each DSB and that can be visualized by immunofluorescent staining. Compared with controls, the repair of radiation-induced DSBs was retarded in H1299 cells pretreated with Ad-PTEN, consistent with the radiosensitizing effect of the vector. We conclude that signal transduction pathways residing primarily in the cytoplasm may intersect with DNA damage and repair pathways in the nucleus to modulate cellular responses to radiation. Elucidating the mechanisms responsible for this intersection may lead to novel strategies for improving therapy for cancers with defective PTEN.

Validity of self-reported 'safe sex' among female sex workers in Mombasa, Kenya--PSA analysis.

We assessed the validity of self-reported sex and condom use by comparing self-reports with prostate-specific antigen (PSA) detection in a prospective study of 210 female sex workers in Mombasa, Kenya. Participants were interviewed on recent sexual behaviours at baseline and 12-month follow-up visits. At both visits, a trained nurse instructed participants to self-swab to collect vaginal fluid specimens, which were tested for PSA using enzyme-linked immunosorbent assay (ELISA). Eleven percent of samples (n = 329) from women reporting no unprotected sex for the prior 48 hours tested positive for PSA. The proportions of women with this type of discordant self-reported and biological data did not differ between the enrolment and 12-month visit (odds ratio [OR] 1.1; 95% confidence interval [CI] 0.99, 1.2). The study found evidence that participants failed to report recent unprotected sex. Furthermore, because PSA begins to clear immediately after exposure, our measures of misreported semen exposure likely are underestimations.