Intersectionality and public understandings of health inequity in England: learning from the views and experiences of young adults.

OBJECTIVES: Attempts to reduce health inequities in England frequently prioritise some equity dimensions over others. Intersectionality highlights how different dimensions of inequity interconnect and are underpinned by historic and institutionalised power imbalances. We aimed to explore whether intersectionality could help us shed light on young adults' understanding of health inequities. STUDY DESIGN: The study incorporatedqualitative thematic analysis of primary data. METHODS: Online focus groups with young adults (n = 25) aged 18-30 living in three English regions (Greater London; South Yorkshire/Midlands; North-East England) between July 2020 and March 2021. Online semistructured interviews (n = 2) and text-based communication was conducted for participants unable to attend online groups. RESULTS: Young adults described experiencing discrimination, privilege, and power imbalances driving health inequity and suggested ways to address this. Forms of inequity included cumulative, within group, interacting, and the experience of privilege alongside marginalisation. Young adults described discrimination occurring in settings relevant to social determinants of health and said it adversely affected health and well-being. CONCLUSION: Intersectionality, with its focus on discrimination and identity, can help public health stakeholders engage with young adults on health equity. An upstream approach to improving health equity should consider multiple and intersecting forms of discrimination along with their cultural and institutional drivers.

Impact of peer support on inpatient and outpatient payments among people with Type 2 diabetes: a prospective cohort study.

AIM: To investigate the impact of a low-cost diabetes peer-support intervention, aimed at reducing inpatient and outpatient care utilization and healthcare payments, by conducting a cohort study that followed up a randomized controlled trial. METHODS: A total of 1121 adults with Type 2 diabetes were recruited through general practices in Cambridgeshire and Hertfordshire, UK, and were followed up for 3.25 financial years after 8-12 months of one-to-one, group or combined diabetes peer support and usual care. Use of, and payments for inpatient and outpatient services were fully recorded in the follow-up. Adjusted mean inpatient and outpatient payments per person were estimated using a two-part model after adjusting for baseline characteristics. RESULTS: The mean age of the recruited adults was 65.6±11.4 years, 60.4% were male, and 16.8% were insulin-treated. Compared with the control group, less healthcare utilization (especially non-elective inpatient care and outpatient consultations) was observed in each of the intervention groups, particularly the combined intervention group. Over the course of 3.25 financial years, significant reductions of 41% (£909.20 per head) were observed for overall inpatient payments (P<0.0001), 51% (£514.67 per head) for non-elective inpatient payments (P=0.005) in the combined intervention group, and 34% (£413.30 per head) and 32% (£388.99 per head) for elective inpatient payments in the one-to-one (P=0.029) and combined intervention (P=0.048) groups, respectively. CONCLUSIONS: Type 2 diabetes peer support, whether delivered using a one-to-one, group or combined approach was associated with reduced inpatient care utilization (particularly non-elective admissions) and payments over 3.25 years.

Bioremediation techniques applied to aqueous media contaminated with mercury.

In recent years, the environmental and human health impacts of mercury contamination have driven the search for alternative, eco-efficient techniques different from the traditional physicochemical methods for treating this metal. One of these alternative processes is bioremediation. A comprehensive analysis of the different variables that can affect this process is presented. It focuses on determining the effectiveness of different techniques of bioremediation, with a specific consideration of three variables: the removal percentage, time needed for bioremediation and initial concentration of mercury to be treated in an aqueous medium.

The disproportionate risk burden of CT scanning on females and younger adults in Australia: a retrospective cohort study.

OBJECTIVES: To explore the interaction of computed tomography (CT) use, dose and radiation risk of Australian Medicare-funded CT scanning and the impact on cancer incidence and mortality. METHODS: This retrospective cohort study used records of Medicare subsidised CT scans in Australia (2006/07 to 2011/12) and Australian CT dosimetry. The annual number, rate and adjusted likelihood of CT were determined for gender, age and examination type. Incident cancer and cancer-related mortality attributable to CT in Australia were estimated using lifetime attributable risk coefficients, dosimetry and scan numbers. RESULTS: The number of CT scans increased by 36% from 2006/07 to 2011/12. Only patients aged 0-4 years did not present an increase in CT scanning rates. Females were 11% more likely to be scanned than males. Head, abdomen/pelvis and spine CT scans were the most likely areas scanned. Females were attributed 61% of both incident cancers and cancer-related mortality from 55% of scans performed. Patients aged 15-44 years were attributed 37% of incident cancers and 30% of cancer-related mortality from 26% of CT scans. CONCLUSIONS: CT in Australia is increasing, including in groups at higher risk from ionising radiation. This presents a complex set of risk/benefit considerations for clinicians and policy makers.

Diagnosing cancer in the bush: a mixed methods study of GP and specialist diagnostic intervals in rural Western Australia.

BACKGROUND: Previous studies have focused on the treatment received by rural cancer patients and have not examined their diagnostic pathways as reasons for poorer outcomes in rural Australia. OBJECTIVES: To compare and explore diagnostic pathways and diagnostic intervals in patients with breast, lung, prostate or colorectal cancer from rural Western Australia (WA) to inform future interventions aimed at reducing time to cancer diagnosis. METHODS: Mixed methods study of people recently diagnosed with breast, lung, prostate or colorectal cancer from the Goldfields and Great Southern Regions of WA. Qualitative interviews explored participants' diagnostic pathways and factors underlying differences observed between individuals and cancers. Data were extracted from general practice and hospital records to calculate intervals from first presentation in general practice to final diagnosis. RESULTS: Sixty-six participants were recruited (43 Goldfields and 23 Great Southern region; 24 breast, 20 colorectal, 14 prostate and 8 lung cancers). There were significant overall differences between cancers in time from presentation in general practice to referral (P = 0.045), from referral to seeing a specialist (P = 0.010) and from specialist appointment to cancer diagnosis (P ≤ 0.001). These differences were due to the nature of presenting symptoms, access to diagnostic tests and multiple visits to specialists. Breast cancer was diagnosed more quickly because its symptoms are more specific and due to better access to diagnostic tests and specialist one-stop clinics. CONCLUSIONS: Interventions to improve cancer diagnosis in rural Australia should focus on better case selection in general practice and better access to diagnostic tests, especially for prostate and colorectal cancers.

The contribution of age and time-to-death on health care expenditure for out-of-hospital services.

OBJECTIVES: Controversy persists over the relationships between health care expenditure, time-to-death and age, undermining attempts to generate convincing predictions for policy. This paper explores the relationships between time-to-death (TTD), age and health care expenditure for Australian Medicare-funded, out-of-hospital services in the last five years of life, assessing if the relationship varies across different types of out-of-hospital services. METHODS: Medicare Benefit Scheme claims for five years before death in Western Australia (1990-2004) pertaining to out-of-hospital primary care, specialist or diagnostic and therapeutic services were used to determine the total and mean per capita health care expenditure (HCE) according to age and TTD. Data were evaluated using univariate linear regression (age) and segmented time-trend regression analysis (time-to-death). RESULTS: Changes to out-of-hospital HCE in the last five years of life did not consistently show a positive association with changes in the number of decedents. Only primary care services demonstrated a linear relationship for HCE and age. For TTD, a linear relationship was observed for all three service types within each retrospective period. CONCLUSIONS: This study has identified significant differences in the relationship between age, TTD and out-of-hospital HCE across service type, further highlighting potential shortcomings in methods that use single, all-service, all-cause models to predict future HCE. These results build on our previous study and suggest that such predictions should either use separate models, or models capable of accounting for the different relationships of HCE with TTD and age across types of services in order to predict future HCE more accurately.

Population versus hospital controls for case-control studies on cancers in Chinese hospitals.

BACKGROUND: Correct control selection is crucial to the internal validity of case-control studies. Little information exists on differences between population and hospital controls in case-control studies on cancers in Chinese hospital setting. METHODS: We conducted three parallel case-control studies on leukemia, breast and colorectal cancers in China between 2009 and 2010, using population and hospital controls to separately match 540 incident cases by age, gender and residency at a 1:1 ratio. Demographic and lifestyle factors were measured using a validated questionnaire in face-to-face interview. Odds ratios (ORs) and 95% confidence intervals (CIs) were obtained using conditional logistic regression analyses. RESULTS: The two control groups had closely similar exposure distributions of 15 out of 16 factors, with the only exception being that hospital controls were less likely to have a BMI ≥ 25 (OR = 0.71, 95% CI: 0.54, 0.93). For exposure of green tea drinking, the adjusted ORs (95% CIs) comparing green tealeaves intake ≥ 1000 grams annually with non-drinkers were 0.51 (0.31, 0.83) and 0.21 (0.27, 0.74) for three cancers combined, 0.06 (0.01, 0.61) and 0.07 (0.01, 0.47) for breast cancer, 0.52 (0.29, 0.94) and 0.45 (0.25, 0.82) for colorectal cancer, 0.65 (0.08, 5.63) and 0.57 (0.07, 4.79) for leukemia using hospital and population controls respectively. CONCLUSIONS: The study found that hospital controls were comparable with population controls for most demographic characteristics and lifestyle factors measured, but there was a slight difference between the two control groups. Hospital outpatients provide a satisfactory control group in hospital-based case-control study in the Chinese hospital setting.

Modulation of ceramide metabolism enhances viral protein apoptin's cytotoxicity in prostate cancer.

Despite local and systemic therapies, the National Cancer Institute estimates that prostate cancer will cause over 30,000 deaths in 2006. This suggests that additional therapeutic approaches are needed. The chicken anemia viral protein Apoptin causes tumor-selective apoptosis in human tumor lines independent of p53 and Bcl-2 status. Tet-regulated expression of Apoptin from an adenoviral vector showed cytotoxicity in DU145, PC-3, and LNCaP tumor cells regardless of expression of p53, Bcl-2, Bcl-xL, Bax, survivin, FLIP(S), XIAP, or CIAP. Apoptin expression caused an increase in the tumor suppressor lipid ceramide, which regulates the cellular stress response. Interestingly, 10 of 15 primary prostate cancers examined by Western blotting overexpressed acid ceramidase (AC), suggesting that ceramide deacylation might serve to negate elevated levels of ceramide, creating a more antiapoptotic phenotype. This was confirmed in AC-overexpressing cells in which we observed decreased sensitivity to apoptosis following treatment with Apoptin. Addition of the AC inhibitor LCL204, in combination with Apoptin, augmented cell killing. This effect was also demonstrated in vivo in that Apoptin and LCL204 cotreatment significantly reduced tumor growth in DU145 xenografts (P<0.05). Taken together, our data demonstrated that Apoptin is a promising therapeutic agent for prostate cancer and that its function is improved when combined with acid ceramidase inhibitors.

Combined therapeutic use of AdGFPFasL and small molecule inhibitors of ceramide metabolism in prostate and head and neck cancers: a status report.

As of January 2005, there were 1020 gene therapy clinical trials ongoing worldwide with 675 or 66.2% devoted to cancer gene therapy. The majority are occurring in the US and Europe (http://www.wiley.co.uk/genetherapy/clinical/). At the present time, to our knowledge there are no trials that employ gene delivery of Fas Ligand (FasL). As an important note, and in contrast to somatic cell therapy trials, there are no reported deaths due to therapeutic vector administration in any cancer gene therapy trial. That said, from our studies and from the published literature, the issue of gene delivery remains the major obstacle to successfully employing gene therapy for cancer treatment. Numerous laboratories are studying this with many different approaches. My co-workers and I have focused on the delivery issue by using various approaches that address tumor targeting and transgene expression. In addition, we are focusing on enhancing tumor cell killing via the bystander effect and through use of small molecules to enhance bystander activity.

Interface between residential aged care facilities and a teaching hospital emergency department in Western Australia.

OBJECTIVE: To estimate the appropriateness of emergency department (ED) presentations by people aged>or=65 years living in residential care facilities. DESIGN, SETTING AND PARTICIPANTS: Retrospective cohort study of older residents of residential care facilities who presented to the ED of the Royal Perth Hospital, Western Australia, between January and June 2002. Data were reviewed by an expert clinical panel. MAIN OUTCOME MEASURES: Appropriateness of ED presentation, presenting complaint, involvement of a general practitioner/locum doctor prior to transfer, proportion of patients admitted to hospital from the ED, survival to discharge. RESULTS: 541 residents aged>or=65 years were transferred by ambulance to the ED, comprising 8.3% of all ED presentations of people in this age group. The mean age of the study cohort was 83.7 years (SD, 7.0 years), of which 68% were women. Of the 541 presentations, 326 (60%) resulted in hospital admission, and of these, 276 (85%) survived to hospital discharge. Musculoskeletal disorders accounted for 25% of all presentations, and 22% were falls-related; pneumonia (11% of presentations) was the single largest presenting complaint. ED attendance was deemed "inappropriate" for 71/541 cases (13.1%; 95% CI, 10.5%-16.2%); in only 25% of ED presentations was a GP/locum doctor involved prior to transfer. CONCLUSIONS: The majority of ED presentations by aged care residents were considered to be appropriate, but there was scope for improvement in coordinating care between the hospital ED and residential care institutions.

Possession of health insurance in Australia--how does it affect hospital use and outcomes?

OBJECTIVE: To assess the effect of possession of private health insurance on hospital use and outcomes in Western Australia. METHOD: Hospital morbidity records were extracted from the Western Australian (WA) Data Linkage System for all 22 major diagnostic categories (MDCs) for the period 1994-99, with follow-up to the end of 2000. Multivariate modelling techniques were used to estimate the effect of possession of private health insurance on hospital admission rates, average and total length of stay (LOS), cumulative incidence of admission at 30 days and one year, and case fatality at one year. RESULTS: Possession of private health insurance had significant effects on hospital use and outcomes, even after adjustments for age, sex, aboriginality, socioeconomic status, location and comorbidity. Non-insured patients tended to have a higher overall hospital admission rate but a lower admission rate for surgical episodes, and they generally had a longer LOS although this difference was only greater than a day in three MDCs. Case fatality was higher in non-insured patients, but there was no systematic trend with regard to readmission rates. CONCLUSIONS: The study found that for all MDCs, other than those where treatment was required on an emergency basis, patients with private health insurance had improved access to surgical procedures. Either non-insured patients were disadvantaged in their access to surgery or the higher intervention rate in privately insured patients represented supplier-/consumer-induced demand which may not always have been to the patient's advantage or both may have occurred.

FasL gene therapy: a new therapeutic modality for head and neck cancer.

In this study, we investigated the in vitro and in vivo efficacy of Fas ligand (FasL) gene therapy for the treatment of head and neck cancer. Three head and neck squamous cell carcinoma (HNSCC) cell lines (SCC-1, SCC-12, and SCC-14a) were treated with the Fas agonist CH-11, a monoclonal antibody to the Fas receptor, or with a replication-incompetent adenovirus (AdGFPFasL) expressing a modified murine Fas ligand gene fused to green fluorescent protein (GFP). A replication-incompetent adenovirus containing the GFP gene alone was used as a control for viral transduction toxicity (AdGFP). Cell death was quantified using a tetrazolium-based (MTS) assay. Cells were analyzed by flow cytometry to determine the expression of adenoviral and Fas receptors on the surface of the cells. Our results showed that the head and neck cancer cell lines are resistant to cell death induction when treated with the anti-Fas monoclonal antibody CH-11. This resistance can be overcome with AdGFPFasL, which was able to induce cell death in all three cell lines. Apoptosis induction was demonstrated using Western blotting by evaluating poly(ADP-ribose) polymerase, and caspase 9 cleavages. In addition, intratumoral injections of AdGFPFasL into SCC-14a xenografts induced significant growth suppression of tumors, indicating that FasL gene therapy may provide a new efficient therapeutic modality for HNSCC that is worthy of a clinical trial.

Ovulation detection methods for urinary hormones: precision, daily and intermittent sampling and a combined hierarchical method.

BACKGROUND: We evaluate the performance of ovulation detection methods and present new approaches, including evaluation of methods for precision, combining multiple markers into a hierarchical system and using ovulation markers in intermittent sampling designs. METHODS: With serum LH peak day as the 'gold standard' of ovulation, we estimated accuracy and precision of ovulation day algorithms using 30 ovulatory menstrual cycles with daily urinary and serum hormones and transvaginal ultrasound. Sensitivity and specificity for estimating the presence of ovulation were tested using visually assessed ovulatory (30) and anovulatory (22) cycles. RESULTS: Sensitivity and specificity ranged from 70 to 100% for estimating presence of ovulation with twice-per-cycle, weekly, twice weekly, every-other-day and daily specimens. A combined hierarchical method estimated ovulation day using daily specimens within +/-2 days of the gold standard in 93% of cases. Accuracy of estimating ovulation day within +/-2 days using intermittent sampling ranged from 40% (weekly sampling) to 97% (every-other-day). CONCLUSIONS: A combined hierarchical algorithm using precise and accurate markers allows maximal use of available data for efficient and objective identification of ovulation using daily specimens. In intermittent sampling designs, the presence and the timing of ovulation can be estimated with good sensitivity, specificity and accuracy.

Osteogenic potential of five different recombinant human bone morphogenetic protein adenoviral vectors in the rat.

Bone morphogenetic protein (BMP) adenoviral vectors for the induction of osteogenesis are being developed for the treatment of bone pathology. However, it is still unknown which BMP adenoviral vector has the highest potential to stimulate bone formation in vivo. In this study, the osteogenic activities of recombinant human BMP-2, BMP-4, BMP-6, BMP-7, and BMP-9 adenoviruses were compared in vitro, in athymic nude rats, and in Sprague-Dawley rats. In vitro osteogenic activity was assessed by measuring the alkaline phosphatase activity in C2C12 cells transduced by the various BMP vectors. The alkaline phosphatase activity induced by 2 x 10(5) PFU/well of BMP viral vector was 4890 x 10(-12) U/well for ADCMVBMP-9, 302 x 10(-12) U/well for ADCMVBMP-4, 220 x 10(-12) U/well for ADCMVBMP-6, 45 x 10(-12) U/well for ADCMVBMP-2, and 0.43 x 10(-12) U/well for ADCMVBMP-7. The average volume of new bone induced by 10(7) PFU of BMP vector in athymic nude rats was 0.37+/-0.03 cm(3) for ADCMVBMP-2, 0.89+/-0.07 cm(3) for ADCMVBMP-4, 1.02+/-0.07 cm(3) for ADCMVBMP-6, 0.24+/-0.05 cm(3) for ADCMVBMP-7, and 0.63+/-0.07 cm(3) for ADCMVBMP-9. In immunocompetent Sprague-Dawley rats, no bone formation was demonstrated in the ADCMVBMP-2, ADCMVBMP-4, and ADCMVBMP-7 groups. ADCMVBMP-6 at a viral dose of 10(8) PFU induced 0.10+/-0.03 cm(3) of new bone, whereas ADCMVBMP-9 at a lower viral dose of 10(7) PFU induced more bone, with an average volume of 0.29+/-0.01 cm(3).

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials.

This report evaluates long-term safety data from 3189 human immunodeficiency virus type 1 (HIV-1) uninfected, healthy volunteers who were enrolled into 51 National Institute of Allergy and Infectious Diseases (NIAID)-sponsored Phase I and II multicentred, randomized, double-blind trials of recombinant HIV-1 subunit vaccines (23 studies), synthetic peptide vaccines (7 studies), live vaccinia-vector recombinant envelope vaccines (7 studies), canarypox vector recombinant vaccines (13 studies), a DNA vaccine (1 study), and a Salmonella-vector vaccine (1 study). During the 12,340 person-years of follow-up, participants were monitored for adverse events including immune dysfunction/autoimmunity, anaphylaxis, cancer, death, and vaccine allergy. The analysis provides evidence that a preparation of a C4-V3 polypeptide vaccine emulsified in incomplete Freund's caused serious toxicity, but otherwise no safety problems considered serious were identified for any of the vaccines and adjuvants studied. These data serve to solidify the growing safety base of current vaccine technologies utilized in candidate vaccines for HIV-1 infection.

Menstrual cycle variability and the perimenopause.

Menopause, the final cessation of menstrual cycling, occurs when the pool of ovarian follicles is depleted. The one to five years just prior to the menopause are usually marked by increasing variability in menstrual cycle length, frequency of ovulation, and levels of reproductive hormones. Little is known about the mechanisms that account for these characteristics of ovarian cycles as the menopause approaches. Some evidence suggests that the dwindling pool of follicles itself is responsible for cycle characteristics during the perimenopausal transition. Another hypothesis is that the increased variability reflects "slippage" of the hypothalamus, which loses the ability to regulate menstrual cycles at older reproductive ages. This paper examines the underlying cause of the increasing variability in menstrual cycle length prior to the menopause. A model of ovarian cycles is developed, based on the process of follicular growth and depletion. Under this model, the follicular phase of each menstrual cycle is preceded by an inactive phase, a period of time when no ovarian follicles have left the resting state and begun secreting steroids in response to gonadotropin stimulation. The model makes predictions about the variability in menstrual cycles across the reproductive life span based on the size of the surviving pool of ovarian follicles. We show that the model can explain several characteristics of the perimenopause in humans and macaques and illustrate how the model can be applied to research on the biological and cultural correlates of the timing of menopause.

Colostrum feeding behaviour and initiation of breast-feeding in rural Bangladesh.

Human breast milk is primarily colostrum immediately following birth. Colostrum gradually changes to mature milk over the next several days. The role of colostrum in fighting infections and promoting growth and development of the newborn is widely acknowledged. This role is mediated by differences across cultures in the acceptability of colostrum and the prevalence of colostrum feeding. This study examined the prevalence of colostrum feeding and time to initiation of breast-feeding in 143 rural Bangladeshi women in Matlab thana. Structured interviews were collected during a 9-month prospective study conducted in 1993. Women were usually interviewed within 4 days of giving birth and were asked about whether or not they fed their child colostrum and the number of hours until they began breast-feeding the baby. Ninety per cent of the mothers reported feeding their newborn colostrum. A logistic regression found no effect on the prevalence of colostrum feeding from the following covariates: mother's age, parity, history of pregnancy loss, child's sex, mother's self-report of delivery complications, and the time from birth to interview. Fifty-nine per cent of mothers initiated breast-feeding within 4 h, and 88% within 12 h of parturition. Survival analysis was used to estimate the effects of covariates on the time from delivery to initial breast-feeding. Time to initial breast-feeding was delayed slightly, but significantly, for older mothers, for male infants, and by mothers who did not report delivery complications. The percentage of mothers who fed their child colostrum was higher, and times to initial breast-feeding were shorter, than almost all previous reports from South Asia. These findings might be explained, in part, by methodological differences among studies, but it is suggested that recent changes towards earlier initiation of breast-feeding have taken place in rural Bangladesh.