Stress-related health depreciation: Using allostatic load to predict self-rated health.

Approximately one quarter of UK adults are currently diagnosed with two or more chronic conditions, often referred to as multimorbidity. Chronic stress has been implicated in the development of many diseases common to multimorbidity. Policymakers and clinicians have acknowledged the need for more preventative approaches to deal with the rise of multimorbidity and "early ageing". However divergence may occur between an individual's self-rated health and objectively measured health that may preclude preventative action. The use of biomarkers which look 'under the skin' provide crucial information on an individual's underlying health to facilitate lifestyle change or healthcare utilisation. The UK's Understanding Society dataset, was used to examine whether baseline variation in biomarkers measuring stress-related "wear and tear" - Allostatic Load (AL) - predict changes in future self-rated health (SRH) while adjusting for baseline SRH, socioeconomic and lifestyle factors, and healthcare inputs. An interaction between baseline AL and baseline SRH was included to test for differential rates of SRH change. We examined SRH using the SF6D instrument, measuring health-related-quality of life (HRQoL), as well as its physical and mental health components separately. We found that HRQoL and physical health decline faster for those with higher baseline AL (indicating greater "wear and tear") however the same pattern was not observed for mental health. These findings provide novel insights for clinicians and policymakers on the usefulness of AL in capturing health trajectories of which individual's may not be aware and its importance in targeting resilience enhancing measures earlier in the lifecourse to delay physical health decline.

COVID-19 pandemic - Inequities and inequalities to exercise and their consequences on the physical and mental health of women with cardiovascular disease: recommendations on how to address the needs of women.

The coronavirus disease (COVID-19) pandemic disproportionately affects those with pre-existing conditions and has exacerbated gender inequalities. Cardiovascular disease (CVD) is the leading cause of death among Canadian women. Exercise improves physical and mental health and CVD management. Amid the pandemic, women are experiencing an increase in caregiving responsibilities, job insecurities, and domestic violence creating competing demands for prioritizing their health. Recommendations on how to meet the unique needs of Canadian women with CVD through exercise are provided. Novelty: Exercise recommendations amid the pandemic for women with CVD need to be flexible, feasible, and fun.

A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment.

OBJECTIVE: To design a reproductive treatment algorithm based on the sperm DNA fragmentation (SDF) for couples with unexplained infertility following a poor intrauterine insemination (IUI) outcome. DESIGN: Couples that failed IUI with no apparent reproductive issue in both partners were allocated to diverse reproductive treatments on the basis of SDF. SETTING: Reproductive medical center in an academic setting. PATIENT(S): Over 4 years, couples with an unexpected poor IUI outcome and no apparent female or male partner reproductive issues were recruited. INTERVENTION(S): IUI, IVF, and ICSI were performed in the standard fashion following sperm SDF assays. MAIN OUTCOMES MEASURE(S): Fertilization rate, implantation rate, pregnancy characteristics, and delivery rates. RESULT(S): A total of 354 couples with unexplained infertility and normal semen parameters underwent 1133 IUI cycles. Clinical pregnancy rate (CPR) with IUI at our center in an age-matched cohort is 23.9% while the study cohort had 1.8%. Following SDF assessment, couples with failed IUI attempts but normal SDF (SCSA 9.8 ± 4.6%; TUNEL 11.8 ± 6.2%) underwent IVF with a CPR of 12.7%; those with abnormal SDF underwent ICSI with ejaculated spermatozoa, resulting in a CPR of 18.7%. This group included couples with normal SDF that had failed IVF. Couples with abnormal SDF that failed ICSI with ejaculated spermatozoa achieved a CPR of 31.0% with surgically retrieved spermatozoa. CONCLUSION(S): Couples with unexplained infertility that present with unexpectedly poor IUI outcomes can be funneled into a treatment algorithm guided by the integrity of the sperm genome for higher chances of pregnancy using an alternate method of insemination.

Cost-effectiveness of secukinumab as first biologic treatment, compared with other biologics, for moderate to severe psoriasis in Germany.

BACKGROUND: Secukinumab, a fully human monoclonal antibody that selectively neutralizes interleukin 17A, has demonstrated strong and sustained efficacy in adults with moderate to severe psoriasis in clinical trials. OBJECTIVE: This analysis compared the cost per responder of secukinumab as first biologic treatment of moderate to severe psoriasis, with adalimumab, infliximab, etanercept and ustekinumab in Germany. METHODS: A 52-week decision-tree model was developed. Response to treatment was assessed based on the likelihood of achieving a predefined Psoriasis Area and Severity Index (PASI) response to separate the cohort into responders (PASI ≥75), partial responders (PASI 50 to 74) and non-responders (PASI <50). Responders at week 16 continued initial treatment, whereas partial responders and non-responders were switched to standard of care, which included methotrexate, cyclosporine, phototherapy and topical corticosteroids. Sustained response was defined as 16-week response maintained at week 52. A German healthcare system perspective was adopted. Clinical efficacy data were obtained from a mixed-treatment comparison; 2016 resource unit costs from national sources; and adverse events and discontinuation rates from the literature. We calculated cost per PASI 90 responder over week 16 and week 52, as well as cost per sustained responder between weeks 16 and 52. RESULTS: Secukinumab had the lowest cost per PASI 90 responder over 16 weeks (€18 026) compared with ustekinumab (€18 080), adalimumab (€23 499), infliximab (€29 599) and etanercept (€34 037). Over 52 weeks, costs per PASI 90 responder ranged from €42 409 (secukinumab) to €70 363 (etanercept). Likewise, secukinumab had the lowest cost per sustained 52-week PASI 90 responder (€22 690) compared with other biologic treatments. Sensitivity analyses, excluding patient copayments, showed similar results. CONCLUSIONS: First biologic treatment with secukinumab for moderate to severe psoriasis is cost-effective, with lowest cost per responder compared with other biologic treatments in Germany.

The cost of systemic corticosteroid-induced morbidity in severe asthma: a health economic analysis.

BACKGROUND: Treatment of severe asthma may include high dose systemic-steroid therapy which is associated with substantial additional morbidity. This study estimates the additional healthcare costs associated with steroid-induced morbidity by comparing three patients groups: those with severe asthma, moderate asthma and no asthma. METHODS: Patients with severe asthma (n = 808, GINA step 5 treatment) were matched by age and gender with patients with mild/moderate asthma (n = 3,975, GINA step 2 and 3 treatment) and a non-asthma control cohort (with a diagnosis of rhinitis; n = 2,412) from the Optimum Patient Care Research Database (OPCRD), a nationally representative primary care database. Prescribed drugs and publicly funded healthcare activity were monetised and annual costs per patient estimated. Regression analyses were used to estimate the additional healthcare cost associated with steroid-induced morbidity. RESULTS: Average healthcare costs per person per year range from £2603 - £4533 for the severe asthma cohort, to £978 - £2072 for the mild/moderate asthma cohort, to £560 - £1324 for the non-asthma control cohort, depending on the costing scenario. Differences in induced morbidity costs were evident between patients with asthma differentiated by steroid exposure. In relation to prescription drugs used to treat steroid-induced co-morbidities, females with severe asthma and high steroid exposure cost approximately £789 more per year than a corresponding female with no asthma, while males cost approximately £744 more than their counterparts with no asthma. Estimates were extrapolated to all healthcare costs. CONCLUSIONS: This study provides the first robust estimates of the additional cost of healthcare related to steroid-induced morbidity relative to patients with no steroid exposure. The study will help inform use of steroid-sparing strategies in this patient group.

Cost-Effectiveness of Caries Prevention in Practice: A Randomized Controlled Trial.

A 2-arm parallel-group randomized controlled trial measured the cost-effectiveness of caries prevention in caries-free children aged 2 to 3 y attending general practice. The setting was 22 dental practices in Northern Ireland. Participants were centrally randomized into intervention (22,600 ppm fluoride varnish, toothbrush, a 50-mL tube of 1,450 ppm fluoride toothpaste, and standardized prevention advice) and control (advice only), both provided at 6-monthly intervals during a 3-y follow-up. The primary outcome measure was conversion from caries-free to caries-active states assessed by calibrated and blinded examiners; secondary outcome measures included decayed, missing, or filled teeth surfaces (dmfs); pain; and extraction. Cumulative costs were related to each of the trial's outcomes in a series of incremental cost effectiveness ratios (ICERs). Sensitivity analyses examined the impact of using dentist's time as measured by observation rather than that reported by the dentist. The costs of applying topical fluoride were also estimated assuming the work was undertaken by dental nurses or hygienists rather than dentists. A total of 1,248 children (624 randomized to each group) were recruited, and 1,096 (549 in the intervention group and 547 in the control group) were included in the final analyses. The mean difference in direct health care costs between groups was £107.53 (£155.74 intervention, £48.21 control, P < 0.05) per child. When all health care costs were compared, the intervention group's mean cost was £212.56 more than the control group (£987.53 intervention, £774.97 control, P < 0.05). Statistically significant differences in outcomes were only detected with respect to carious surfaces. The mean cost per carious surface avoided was estimated at £251 (95% confidence interval, £454.39-£79.52). Sensitivity analyses did not materially affect the study's findings. This trial raises concerns about the cost-effectiveness of a fluoride-based intervention delivered at the practice level in the context of a state-funded dental service (EudraCT No: 2009-010725-39; ISRCTN: ISRCTN36180119).

The Cost of Blindness in the Republic of Ireland 2010-2020.

Aims. To estimate the prevalence of blindness in the Republic of Ireland and the associated financial and total economic cost between 2010 and 2020. Methods. Estimates for the prevalence of blindness in the Republic of Ireland were based on blindness registration data from the National Council for the Blind of Ireland. Estimates for the financial and total economic cost of blindness were based on the sum of direct and indirect healthcare and nonhealthcare costs. Results. We estimate that there were 12,995 blind individuals in Ireland in 2010 and in 2020 there will be 17,997. We estimate that the financial and total economic costs of blindness in the Republic of Ireland in 2010 were €276.6 million and €809 million, respectively, and will increase in 2020 to €367 million and €1.1 billion, respectively. Conclusions. Here, ninety-eight percent of the cost of blindness is borne by the Departments of Social Protection and Finance and not by the Department of Health as might initially be expected. Cost of illness studies should play a role in public policy making as they help to quantify the indirect or "hidden" costs of disability and so help to reveal the true cost of illness.

Short- and long-term effects of gestational diabetes mellitus on healthcare cost: a cross-sectional comparative study in the ATLANTIC DIP cohort.

AIMS: This paper examines the association between gestational diabetes mellitus and costs of care during pregnancy and 2-5 years post pregnancy. METHODS: Healthcare utilization during pregnancy was measured for a sample of 658 women drawn from the Atlantic Diabetes in Pregnancy (ATLANTIC DIP) network. Healthcare utilization 2-5 years post pregnancy was assessed for a subsample of 348 women via a postal questionnaire. A vector of unit costs was applied to healthcare activity to calculate the costs of care at both time points. Differences in cost for women with gestational diabetes mellitus compared with those with normal glucose tolerance during the pregnancy were examined using univariate and multivariate regression analyses. RESULTS: Gestational diabetes mellitus was independently associated with an additional €817.60 during pregnancy (€1192.1 in the gestational diabetes mellitus group, €511.6 in the normal glucose tolerance group), in the form of additional delivery and neonatal care costs, and an additional €680.50 in annual healthcare costs 2-5 years after the index pregnancy (€6252.4 in the gestational diabetes mellitus group, €5434.8 in the normal glucose tolerance group). CONCLUSIONS: These results suggest that gestational diabetes mellitus is associated with increased costs of care during and post pregnancy. They provide indication of the associated cost that can be avoided or reduced by the screening, prevention and management of gestational diabetes mellitus in pregnancy. These estimates are useful for further studies that examine the cost and cost-effectiveness of such programmes.

Value of an active surveillance policy to document clearance of meticillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci amongst inpatients with prolonged admissions.

This article reports the impact of an active surveillance policy to identify clearance of meticillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE) in known colonized inpatients with prolonged admissions in order to discontinue isolation precautions. Amongst 365 colonized patients with hospital admissions exceeding 30 days, clearance rates of 11% for MRSA and 18% for VRE were found after a median of 23 days and 26.5 days, respectively, resulting in a saving of 2152 patient-days of contact precautions over one year. This has proven to be a cost-beneficial policy.

Estimating the health-care usage associated with osteoarthritis and rheumatoid arthritis in an older adult population in Ireland.

BACKGROUND: An ageing population leads to increasing prevalence of age-related chronic conditions that present challenges to the health-care services. Despite this, in countries including Ireland, little is known about the health-care impact of conditions such as osteoarthritis or rheumatoid arthritis amongst older adults. METHODS: A series of count models are developed to investigate the incremental health-care usage of individuals with either osteoarthritis or rheumatoid arthritis on the use of general practitioners (GP) services, outpatients' services, accident and emergency visits and inpatient nights. RESULTS: Both types of arthritic conditions lead to increased usage of GP and outpatients' services but not other hospital services. Differences in entitlements to care, as captured by the presence of a medical card in Ireland, lead to different health-care usage among arthritis sufferers. Translating the additional utilization into cost suggests a combined incremental annual cost of both types of arthritis of €13.6 million. CONCLUSIONS: Osteoarthritis and rheumatoid arthritis present challenges to health-care services in the context of an ageing population. In the case of Ireland the burden falls predominantly on primary health-care and outpatient services. Within the context of changing health-care service provision in Ireland, the results of this study have implications for future planning of service delivery.

The number of tPSA tests continues to rise and variation in testing practices persists: a survey of laboratory services in Ireland 2008-2010.

BACKGROUND: Ireland had the highest incidence of prostate cancer in Europe in 2008, due to widespread prostate specific antigen (PSA) testing. AIMS: To investigate practices and costs of PSA testing in Ireland, 2008-2010. METHODS: Postal laboratory questionnaire. Results were compared with 2006 and 2007 surveys. RESULTS: Response rate was 95 % (42/44). In 2010, 37 laboratories measured total PSA (tPSA); 10 measured free PSA (fPSA). Eight assays were used and cut-offs to define 'normal' tPSA varied widely. There was a 9.9 % annual increase in the number of tPSA tests and a -31 % annual decrease in the number of fPSA, 2006-2010. A 100-fold difference in tPSA workload was observed across laboratories. In 2010, the estimated cost of PSA testing was 3,649,984 (95 % CI 2,532,745-4,767,222). CONCLUSIONS: Health service costs of PSA testing are significant. The number of tPSA tests continues to rise; fPSA use fell by almost one-third. Inter-laboratory variation in testing practices persists. These have potentially important clinical consequences for men and need to be addressed.

Description and predictors of hospital costs of oesophageal cancer during the first year following diagnosis in Northern Ireland.

The cost-effectiveness of novel interventions in the treatment of cancer is well researched; however, relatively little attention is paid to the cost of many aspects of routine care. Oesophageal cancer is the ninth most common cancer in the UK and sixth most common cause of cancer death. It usually presents late and has a poor prognosis. The hospital costs incurred by oesophageal cancer patients diagnosed in Northern Ireland in 2005 (n = 198) were determined by review of medical records. The average cost of hospital care per patient in the 12 months from presentation was £7847. Variations in total hospital costs by age at diagnosis, gender, cancer stage, histological type, mortality at 1 year, co-morbidity count and socio-economic status were analysed using multiple regression analyses. Higher costs were associated with earlier stages of cancer and cancer stage remained a significant predictor of costs after controlling for cancer type, patient age and mortality at 1 year. Thus, although early detection of cancer usually improves survival, this would mean increased costs in the first year. Deprivation achieved borderline significance with those from more deprived areas having lower resource consumption relative to the more affluent.

New estimates of the costs of universal screening for gestational diabetes mellitus in Ireland.

The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria have been predicted to increase the prevalence of gestational diabetes mellitus 2-to-3 fold and will have important resource implications for healthcare systems. A bottom-up, prevalence-based analysis was undertaken to estimate the costs of universal screening for gestational diabetes mellitus in Ireland using the new criteria. Healthcare activity was identified from the Atlantic Diabetes in Pregnancy database and grouped into five categories: (i) screening and testing, (ii) GDM treatment, (iii) prenatal care, (iv) delivery care, and (v) neonatal care. When individual resource components were valued using unit cost data and aggregated, the total healthcare cost was estimated at Euro 46,311,301 (95% CI: Euro 36,381,038, Euro 68,007,432). The average cost per case detected was Euro 351 (95% CI: (Euro 126, Euro 558) and the average total cost per case detected and treated was Euro 9,325 (95% CI: Euro 5,982, Euro 13,996). Further research is required to determine the cost effectiveness of screening in the region with a view to improving resource allocation in this area in the future.

The cost of universal screening for gestational diabetes mellitus in Ireland.

AIMS: To estimate the costs associated with universal screening for gestational diabetes mellitus in Ireland. METHODS: Bottom-up, prevalence-based cost analysis. Healthcare activity identified using the Atlantic Diabetes in Pregnancy (ATLANTIC DIP) database was grouped into five categories: screening and testing, gestational diabetes treatment, prenatal care, delivery care and neonatal care. A vector of unit cost data (euros in 2008 prices) was applied to specified resource use and the total healthcare cost calculated. A series of one-way and probabilistic sensitivity analyses were undertaken to explore the uncertainty in the analysis. RESULTS: When individual resource components were valued and aggregated, the total healthcare cost of gestational diabetes in Ireland was estimated at €12 433 320 (95% CI €9 298 228-16 778 193). The average cost per case detected was €1621 (95% CI €524-2603) and the average total cost per case detected and treated was €11 903 (95% CI €7645-16 121). CONCLUSIONS: This research provides the first estimates of the healthcare costs associated with gestational diabetes mellitus in Ireland. Further research is required to determine the cost-effectiveness of gestational diabetes screening in the region with a view to improving resource allocation in this area in the future.

The role of magnetic resonance imaging in the identification of suspected acoustic neuroma: a systematic review of clinical and cost effectiveness and natural history.

OBJECTIVE(S): To evaluate the clinical effectiveness and cost-effectiveness of a range of diagnostic strategies for investigating patients with unilateral hearing loss and/or tinnitus, with a view to confirming or eliminating a diagnosis of acoustic neuroma, and to describe the natural history of acoustic neuroma. DATA SOURCES: Major electronic databases were searched from January 1980 to August 2008. REVIEW METHODS: Selected studies were assessed and subjected to data extraction and quality assessment using standard methods. RESULTS: Studies comparing auditory brainstem response (ABR) with magnetic resonance (MR) imaging were highly heterogeneous. ABR has high sensitivity compared with MR imaging for acoustic neuromas greater than 1 cm in size but not for smaller neuromas. The sensitivities of T2-weighted (T2W) and T2-star-weighted (T2*W) imaging strategies compared with gadolinium-enhanced T1-weighted (GdT1W) MR imaging (gold standard) were high and relatively homogeneous. The specificity of T2W and T2*W studies ranged from 90% to 100% and from 86% to 99% respectively. The review of cost-effectiveness showed that GdT1W MR imaging immediately or in conjunction with ABR appears to be more cost-effective than 'traditional' protocols; ABR/GdT1W MR imaging protocols were more cost-effective than going directly to GdT1W MR imaging. Non-contrast-enhanced MR imaging was found to be a more cost-effective test for acoustic neuroma than GdT1W MR imaging. The incidence of acoustic neuroma has increased over the last 30 years, with the median age at diagnosis remaining at 55 years. Most patients present with insidious symptoms of unilateral hearing impairment, tinnitus and/or vertigo. The pattern and rate of growth of acoustic neuroma are highly variable and currently unpredictable. At least 50% of tumours do not grow, at least for some years after diagnosis. Some studies have found large initial size to be a determinant of later growth, with the opposite also being reported. The mean growth rate for all tumours varies between 1 and 2 mm/year, with a rate of 2-4 mm/year for only those that grow; however, there are cases with significant regression (5%) or exceptional growth (which may exceed 18 mm/year). CONCLUSIONS: The majority of the evidence reviewed was poorly reported and there is therefore an inherent risk of bias. Given the recent improvement in resolution and reduction in cost of MR imaging, ABR can no longer be considered appropriate as the primary test used to screen for acoustic neuroma. T2W or T2*W sequences enable accurate evaluation of the VIIIth and VIIth cranial nerves within the cerebellopontine angle and internal auditory canal as well as evaluation of the cochlea and labyrinth, and inclusion of GdT1W sequences is unlikely to contribute information that would alter patient management in the screening population. The quality of the imaging chain and experience of the reporting radiologist are key factors determining the efficacy of a non-contrast screening strategy. Based on a cost-effectiveness model developed to reflect UK practice it was concluded that a diagnostic algorithm that deploys non-contrast MR imaging as an initial imaging screen in the investigation of acoustic neuroma is less costly than and likely to be as effective as available contrast MR imaging.

The role of non-need factors in individual GP utilisation analysis and their implications for the pursuance of equity: a cross-country comparison.

A substantial amount of health care resources is allocated within the UK using formulae that relate funding to measures of population need. The aim of this paper is to demonstrate the importance of non-need factors in determining utilisation of services at an individual level and explore the implications inclusion of such factors has in the consideration of equity. In the paper we develop a utility model that accords a role to non-health factors in the determination of service use. A series of functions incorporating non-health factors as explanatory variables in GP utilisation functions are estimated using data from the British Household Panel Survey. The functions are decomposed to ascertain the role of service structure and examine the role of income across the four countries of the UK in explaining utilisation. The implications of our findings for the pursuance of equity in the NHS when individual choice has an explicit role are discussed.

Assessment of the long-term and transgenerational consequences of perturbing preimplantation embryo development in mice.

Perturbations of the development of preimplantation embryos may have long-term consequences for the health of progeny. There are no standardized methods for assessing such risks. The OECD/OCDE 416 Guideline for Testing of Chemicals (Two-Generation Reproduction Toxicity Study) is a standardized assay for detecting potential toxic effects of chemicals. The present study assessed the utility of this guideline for identifying long-term consequences of perturbing preimplantation development. Extended culturing of mammalian zygotes commonly results in retarded preimplantation development. Mouse zygotes were cultured in vitro for 96 h until the blastocyst stage (cultured blastocysts) or blastocysts were collected from the Day-3.5 uterus (in vivo blastocysts). The resulting blastocysts were transferred to the uteri of pseudopregnant recipients (P generation). Progeny from both treatments were mated for a further two generations (F1 and F2 generations). There was no effect of treatment group on gross fertility across the generations tested. Progeny of the cultured blastocysts had lower body weights to the time of weaning compared to in vivo blastocysts in the P and F1 generations, but not in the F2 generation. At maturity, there was no effect of treatment group on body weight, although thyroid weight was higher in the in vivo blastocyst group in the P generation, while the brain, pituitary, and kidneys were larger in the progeny of the cultured blastocysts of the F1 generation. The OECD/OCDE 416 assessment may have a role as a standardized test for the assessment of the biological consequences of perturbing the growth environment of the preimplantation embryo. Embryo culture influenced the somatometric parameters of the resulting progeny, some of which were maintained across a generation.