Healthcare resource utilization and related financial costs associated with glucose lowering with either exenatide or basal insulin: a retrospective cohort study

Aims Type 2 diabetes is a major health problem placing increasing demands on healthcare systems. Our objective was to estimate healthcare resource use and related financial costs following treatment with exenatide‐based regimens prescribed as once‐weekly (EQW) or twice‐daily (EBID) formulations, compared with regimens based on basal insulin (BI). Materials and methods This retrospective cohort study used data from the UK Clinical Practice Research Datalink (CPRD) linked to Hospital Episode Statistics (HES). Patients with type 2 diabetes who received exenatide or BI between 2009 and 2014 as their first recorded exposure to injectable therapy were selected. Costs were attributed to primary care contacts, diabetes‐related prescriptions and inpatient admissions using standard UK healthcare costing methods (2014 prices). Frequency and costs were compared between cohorts before and after matching by propensity score using Poisson regression. Results Groups of 8723, 218 and 2180 patients receiving BI, EQW and EBID, respectively, were identified; 188 and 1486 patients receiving EQW and EBID, respectively, were matched 1:1 to patients receiving BI by propensity score. Among unmatched cohorts, total crude mean costs per patient‐year were £2765 for EQW, £2549 for EBID and £4080 for BI. Compared with BI, the adjusted annual cost ratio (aACR) was 0.92 (95% CI, 0.91‐0.92) for EQW and 0.82 (95% CI, 0.82‐0.82) for EBID. Corresponding costs for the propensity‐matched subgroups were £2646 vs £3283 (aACR, 0.80, 0.80‐0.81) for EQW vs BI and £2532 vs £3070 (aACR, 0.84, 0.84‐0.84) for EBID vs BI. Conclusion Overall, exenatide once‐weekly and twice‐daily‐based regimens were associated with reduced healthcare resource use and costs compared with basal‐insulin‐based regimens

Non-Response to Antibiotic Treatment in Adolescents for Four Common Infections in UK Primary Care 1991-2012: A Retrospective, Longitudinal Study

We studied non-response rates to antibiotics in the under-reported subgroup of adolescents aged 12 to 17 years old, using standardised criteria representing antibiotic treatment failure. Routine, primary care data from the UK Clinical Practice Research Datalink (CPRD) were used. Annual, non-response rates by antibiotics and by indication were determined. We identified 824,651 monotherapies in 415,468 adolescents: 368,900 (45%) episodes for upper respiratory tract infections (URTIs), 89,558 (11%) for lower respiratory tract infections (LRTIs), 286,969 (35%) for skin/soft tissue infections (SSTIs) and 79,224 (10%) for acute otitis media (AOM). The most frequently prescribed antibiotics were amoxicillin (27%), penicillin-V (24%), erythromycin (11%), flucloxacillin (11%) and oxytetracycline (6%). In 1991, the overall non-response rate was 9.3%: 11.9% for LRTIs, 9.5% for URTIs, 7.1% for SSTIs, 9.7% for AOM. In 2012, the overall non-response rate was 9.2%. Highest non-response rates were for AOM in 1991–1999 and for LRTIs in 2000–2012. Physicians generally prescribed antibiotics to adolescents according to recommendations. Evidence of antibiotic non-response was less common among adolescents during this 22-year study period compared with an all-age population, where the overall non-response rate was 12%

Precision Astrometry of a Sample of Speckle Binaries and Multiples with the Adaptive Optics Facilities at the Hale and Keck II Telescopes

Using the adaptive optics facilities at the 200-in Hale and 10-m Keck II, we observed in the near infrared a sample of 12 binary and multiple stars and one open cluster. We used the near diffraction limited images of these systems to measure the relative separations and position angles between their components. In this paper, we investigate and correct for the influence of the differential chromatic refraction and chip distortions on our relative astrometric measurements. Over one night, we achieve an astrometric precision typically well below 1 miliarcsecond and occasionally as small as 40 microarcseconds. Such a precision is in principle sufficient to astrometrically detect planetary mass objects around the components of nearby binary and multiple stars. Since we have not had sufficiently large data sets for the observed sample of stars to detect planets, we provide the limits to planetary mass objects based on the obtained astrometric precision.Comment: 18 pages, 8 figures, 9 tables, to appear in MNRA

Characterization and Associated Costs of Constipation Relating to Exposure to Strong Opioids in England: An Observational Study

PurposeOpioid use is associated with gastrointestinal adverse events, including nausea and constipation. We used a real-world dataset to characterize the health care burden associated with opioid-induced constipation (OIC) with particular emphasis on strong opioids.MethodsThis retrospective cohort study was conducted using the Clinical Practice Research Datalink, a large UK primary care dataset linked to hospital data. Patients prescribed opioids during 2016 were selected and episodes of opioid therapy constructed. Episodes with ≥84 days of exposure were classified as chronic, with date of first prescription as the index date. The main analysis focused on patients prescribed strong opioids who were laxative naive. Constipation was defined by ≥2 laxative prescriptions during the opioid episode. Patients for whom initial laxative therapy escalated by switch, augmentation, or dose were defined as OIC unstable, and the first 3 lines of OIC escalation were classified. Health care costs accrued in the first 12 months of the opioid episode were aggregated and compared.FindingsA total of 27,629 opioid episodes were identified; 5916 (21.4%) involved a strong opioid for patients who were previously laxative naive. Of these patients, 2886 (48.8%) were defined as the OIC population; 941 (33.26%) were classified as stable. Of the 1945 (67.4%) episodes classified as unstable, 849 (43.7%), 360 (18.5%), and 736 (37.8%) had 1, 2, and ≥3 changes of laxative prescription, respectively. Patients without OIC had lower costs per patient year (£3822 [US$5160/€4242]) compared with OIC (£4786 [US$6461/€5312]). Costs increased as patients had multiple changes in therapy: £4696 (US$6340/€5213), £4749 (US$6411/€5271), and £4981 (US$6724/€5529) for 1, 2, and ≥3 changes, respectively. The adjusted cost ratio relative to non-OIC was 1.14 (95$5031/€4137] vs £2379 [US$3212 /€2641),and for those patients classified as unstable versus stable (£3931 [US$5307/€4363] vs £3432 [US$4633/€3810). Costs increased with each additional line of therapy from £3701 (US$4996/€4108), £3916 (US$5287/€4347), and £4318 (US$5829/€4793).ImplicationsOIC was a common adverse event of opioid treatment and was poorly controlled for a large number of patients. Poor control was associated with increased health care costs. The impact of OIC should be considered when prescribing opioids. These results should be interpreted with consideration of the caveats associated with the analysis of routine data

Impact of Indian Total Sanitation Campaign on latrine coverage and use: a cross-sectional study in Orissa three years following programme implementation.

BACKGROUND: Faced with a massive shortfall in meeting sanitation targets, some governments have implemented campaigns that use subsidies focused on latrine construction to overcome income constraints and rapidly expand coverage. In settings like rural India where open defecation is common, this may result in sub-optimal compliance (use), thereby continuing to leave the population exposed to human excreta. METHODS: We conducted a cross-sectional study to investigate latrine coverage and use among 20 villages (447 households, 1933 individuals) in Orissa, India where the Government of India's Total Sanitation Campaign had been implemented at least three years previously. We defined coverage as the proportion of households that had a latrine; for use we identified the proportion of households with at least one reported user and among those, the extent of reported use by each member of the household. RESULTS: Mean latrine coverage among the villages was 72% (compared to <10% in comparable villages in the same district where the Total Sanitation Campaign had not yet been implemented), though three of the villages had less than 50% coverage. Among these households with latrines, more than a third (39%) were not being used by any member of the household. Well over a third (37%) of the members of households with latrines reported never defecating in their latrines. Less than half (47%) of the members of such households reported using their latrines at all times for defecation. Combined with the 28% of households that did not have latrines, it appears that most defecation events in these communities are still practiced in the open. CONCLUSION: A large-scale campaign to implement sanitation has achieved substantial gains in latrine coverage in this population. Nevertheless, gaps in coverage and widespread continuation of open defecation will result in continued exposure to human excreta, reducing the potential for health gains

West Nile Virus Experimental Evolution in vivo and the Trade-off Hypothesis

In nature, arthropod-borne viruses (arboviruses) perpetuate through alternating replication in vertebrate and invertebrate hosts. The trade-off hypothesis proposes that these viruses maintain adequate replicative fitness in two disparate hosts in exchange for superior fitness in one host. Releasing the virus from the constraints of a two-host cycle should thus facilitate adaptation to a single host. This theory has been addressed in a variety of systems, but remains poorly understood. We sought to determine the fitness implications of alternating host replication for West Nile virus (WNV) using an in vivo model system. Previously, WNV was serially or alternately passed 20 times in vivo in chicks or mosquitoes and resulting viruses were characterized genetically. In this study, these test viruses were competed in vivo in fitness assays against an unpassed marked reference virus. Fitness was assayed in chicks and in two important WNV vectors, Culex pipiens and Culex quinquefasciatus. Chick-specialized virus displayed clear fitness gains in chicks and in Cx. pipiens but not in Cx. quinquefasciatus. Cx. pipiens-specialized virus experienced reduced fitness in chicks and little change in either mosquito species. These data suggest that when fitness is measured in birds the trade-off hypothesis is supported; but in mosquitoes it is not. Overall, these results suggest that WNV evolution is driven by alternate cycles of genetic expansion in mosquitoes, where purifying selection is weak and genetic diversity generated, and restriction in birds, where purifying selection is strong

In vitro and in vivo studies on biocompatibility of carbon fibres

In the present study we focused on the in vitro and in vivo evaluation of two types of carbon fibres (CFs): hydroxyapatite modified carbon fibres and porous carbon fibres. Porous CFs used as scaffold for tissues regeneration could simultaneously serve as a support for drug delivery or biologically active agents which would stimulate the tissue growth; while addition of nanohydroxyapatite to CFs precursor can modify their biological properties (such as bioactivity) without subsequent surface modifications, making the process cost and time effective. Presented results indicated that fibre modification with HAp promoted formation of apatite on the fibre surface during incubation in simulated body fluid. The materials biocompatibility was determined by culturing human osteoblast-like cells of the line MG 63 in contact with both types of CFs. Both tested materials gave good support to adhesion and growth of bone-derived cells. Materials were implanted into the skeletal rat muscle and a comparative analysis of tissue reaction to the presence of the two types of CFs was done. Activities of marker metabolic enzymes: cytochrome c oxidase (CCO) and acid phosphatase were examined to estimate the effect of implants on the metabolic state of surrounding tissues. Presented results evidence the biocompatibility of porous CFs and activity that stimulates the growth of connective tissues. In case of CFs modified with hydroxyapatite the time of inflammatory reaction was shorter than in case of traditional CFs

Estimating the long-term impact of a prophylactic human papillomavirus 16/18 vaccine on the burden of cervical cancer in the UK

To predict the public health impact on cervical disease by introducing human papillomavirus (HPV) vaccination in the United Kingdom, we developed a mathematical model that can be used to reflect the impact of vaccination in different countries with existing screening programmes. Its use is discussed in the context of the United Kingdom. The model was calibrated with published data. The impact of vaccination on cervical cancer and deaths, precancerous lesions and screening outcomes were estimated for a vaccinated cohort of 12-year-old girls, among which it is estimated that there would be a reduction of 66% in the prevalence of high-grade precancerous lesions and a 76% reduction in cervical cancer deaths. Estimates for various other measures of the population effects of vaccination are also presented. We concluded that it is feasible to forecast the potential effects of HPV vaccination in the context of an existing national screening programme. Results suggest a sizable reduction in the incidence of cervical cancer and related deaths. Areas for future research include investigation of the beneficial effects of HPV vaccination on infection transmission and epidemic dynamics, as well as HPV-related neoplasms in other sites