Retrospective, multicohort analysis of the Clinical Practice Research Datalink (CPRD) to determine differences in the cost of medication wastage, dispensing fees and prescriber time of issuing either short (<60 days) or long (≥60 days) prescription lengths in primary care for common, chronic conditions in the UK.

OBJECTIVES: To investigate patterns of early repeat prescriptions and treatment switching over an 11-year period to estimate differences in the cost of medication wastage, dispensing fees and prescriber time for short (<60 days) and long (≥60 days) prescription lengths from the perspective of the National Health Service in the UK. SETTING: Retrospective, multiple cohort study of primary care prescriptions from the Clinical Practice Research Datalink. PARTICIPANTS: Five random samples of 50 000 patients each prescribed oral drugs for (1) glucose control in type 2 diabetes mellitus (T2DM); (2) hypertension in T2DM; (3) statins (lipid management) in T2DM; (4) secondary prevention of myocardial infarction; and (5) depression. PRIMARY AND SECONDARY OUTCOME MEASURES: The volume of medication wastage from early repeat prescriptions and three other types of treatment switches was quantified and costed. Dispensing fees and prescriber time were also determined. Total unnecessary costs (TUC; cost of medication wastage, dispensing fees and prescriber time) associated with <60 day and ≥60 day prescriptions, standardised to a 120-day period, were then compared. RESULTS: Longer prescription lengths were associated with more medication waste per prescription. However, when including dispensing fees and prescriber time, longer prescription lengths resulted in lower TUC. This finding was consistent across all five cohorts. Savings ranged from £8.38 to £12.06 per prescription per 120 days if a single long prescription was issued instead of multiple short prescriptions. Prescriber time costs accounted for the largest component of TUC. CONCLUSIONS: Shorter prescription lengths could potentially reduce medication wastage, but they may also increase dispensing fees and/or the time burden of issuing prescriptions.This research was supported by a grant from the National Institute for Health Research, Health Technology Assessment funding stream (Grant Reference: NIHR HTA 14/159/07)

Impairment in Activities of Daily Living and unmet need for care among older adults: A population-based study from Burkina Faso

OBJECTIVES: The importance of impairment in performing Activities of Daily Living (ADL) is likely to increase in sub-Saharan Africa since few care options for affected people exist. This study investigated the prevalence of ADL impairment, the extent to which care-need was met and described characteristics of people with ADL impairment and unmet need in Burkina Faso. METHODS: This study used data from the CRSN Heidelberg Aging Study, a population-based study among 3,026 adults aged over 40 years conducted in rural Burkina Faso. Information on six basic ADL items was sought, with a follow-up question asking whether care-needs were not met, partially met or met. Bivariable correlations and multivariable logistic regression were used to determine sociodemographic and health characteristics associated with ADL impairment and unmet need. RESULTS: ADL impairment of any kind was reported by 1,202 (39.7%) respondents and was associated with older age (Adjusted Odds Ratio: 1.05 [95% CI: 1.04-1.06]), being a woman (1.33 [1.06-1.60]) and reporting depressive symptoms (1.90 [1.65-2.18]). Among those with ADL impairment, 67.8% had at least one unmet need. Severe ADL impairment was found in 202 (6.7%) respondents, who reported lower prevalence of unmet need (43.1%). Severe ADL impairment was associated with depressive symptoms (2.55 [2.11-3.07]) to a stronger degree than any ADL impairment. DISCUSSION: Prevalence of ADL impairment and unmet need was high in this setting. Variation in impairment across the population highlighted key groups for future interventions. Unmet need for care was highest in middle-aged adults, indicating a gap in care provision

Household Transmission of Rotavirus in a Community with Rotavirus Vaccination in Quininde, Ecuador

Background: We studied the transmission of rotavirus infection in households in peri-urban Ecuador in the vaccination era. Methods: Stool samples were collected from household contacts of child rotavirus cases, diarrhea controls and healthy controls following presentation of the index child to health facilities. Rotavirus infection status of contacts was determined by RT-qPCR. We examined factors associated with transmissibility (index-case characteristics) and susceptibility (householdcontact characteristics). Results: Amongst cases, diarrhea controls and healthy control household contacts, infection attack rates (iAR) were 55%, 8% and 2%, (n = 137, 130, 137) respectively. iARs were higher from index cases with vomiting, and amongst siblings. Disease ARs were higher when the index child was ,18 months and had vomiting, with household contact ,10 years and those sharing a room with the index case being more susceptible. We found no evidence of asymptomatic infections leading to disease transmission. Conclusion: Transmission rates of rotavirus are high in households with an infected child, while background infections are rare. We have identified factors associated with transmission (vomiting/young age of index case) and susceptibility (young age/sharing a room/being a sibling of the index case). Vaccination may lead to indirect benefits by averting episodes or reducing symptoms in vaccinees

Impairment in Activities of Daily Living, Care Receipt, and Unmet Needs in a Middle-Aged and Older Rural South African Population: Findings From the HAALSI Study

OBJECTIVES: The objective of this study is to analyze the degree to which care needs are met in an aging rural African population. METHOD: Using data from the Health and Aging in Africa: Longitudinal Study of an INDEPTH Community (HAALSI) baseline survey, which interviewed 5,059 adults aged older than 40 years in rural South Africa, we assessed the levels of limitations in activities of daily living (ADLs) and in unmet care for these ADLs, and evaluated their association with sociodemographic and health characteristics. RESULTS: ADL impairment was reported by 12.2% of respondents, with the proportion increasing with age. Among those with ADL impairment, 23.9% reported an unmet need and 51.4% more a partially met need. Relatives provided help most often; formal care provision was rare. Unmet needs were more frequent among younger people and women, and were associated with physical and cognitive deficits, but not income or household size. DISCUSSION: Unmet care needs in rural South Africa are often found among individuals less expected to require care

A Survey on the Krein-von Neumann Extension, the corresponding Abstract Buckling Problem, and Weyl-Type Spectral Asymptotics for Perturbed Krein Laplacians in Nonsmooth Domains

In the first (and abstract) part of this survey we prove the unitary equivalence of the inverse of the Krein--von Neumann extension (on the orthogonal complement of its kernel) of a densely defined, closed, strictly positive operator, $S\geq \varepsilon I_{\mathcal{H}}$ for some $\varepsilon >0$ in a Hilbert space $\mathcal{H}$ to an abstract buckling problem operator. This establishes the Krein extension as a natural object in elasticity theory (in analogy to the Friedrichs extension, which found natural applications in quantum mechanics, elasticity, etc.). In the second, and principal part of this survey, we study spectral properties for $H_{K,\Omega}$, the Krein--von Neumann extension of the perturbed Laplacian $-\Delta+V$ (in short, the perturbed Krein Laplacian) defined on $C^\infty_0(\Omega)$, where $V$ is measurable, bounded and nonnegative, in a bounded open set $\Omega\subset\mathbb{R}^n$ belonging to a class of nonsmooth domains which contains all convex domains, along with all domains of class $C^{1,r}$, $r>1/2$.Comment: 68 pages. arXiv admin note: extreme text overlap with arXiv:0907.144

Ocean warming threatens southern right whale population recovery

Funding: This work was supported by CAPES doctoral scholarship (M.A.), CAPES-PRINT grant 88887.370641/2019-00 (M.A.), CNPQ research grant 305573/2013-6 (P.C.S.-L.), and CNPQ research grant 407190/2012-0 (F.G.D.-J.). Funding for aerial surveys since 1971 was provided by numerous donors through Ocean Alliance and Instituto de Conservación de Ballenas such as Wildlife Conservation Society, National Geographic Society, World Wildlife Fund, Alfredo Fortabat Foundation, Turner Foundation, Canadian Whale Institute, I. Kerr, A. L. de Fortabat, S. Haney, A. and J. Moss, A. Morse, P. Singh, P. Logan, N. Griffis, and C. Walcott.Whales contribute to marine ecosystem functioning, and they may play a role in mitigating climate change and supporting the Antarctic krill (Euphausia superba) population, a keystone prey species that sustains the entire Southern Ocean (SO) ecosystem. By analyzing a five-decade (1971–2017) data series of individual southern right whales (SRWs; Eubalaena australis) photo-identified at Península Valdés, Argentina, we found a marked increase in whale mortality rates following El Niño events. By modeling how the population responds to changes in the frequency and intensity of El Niño events, we found that such events are likely to impede SRW population recovery and could even cause population decline. Such outcomes have the potential to disrupt food-web interactions in the SO, weakening that ecosystem’s contribution to the mitigation of climate change at a global scale.Publisher PDFPeer reviewe

Lung adenocarcinoma originates from retrovirus infection of proliferating type 2 pneumocytes during pulmonary post-natal development or tissue repair

Jaagsiekte sheep retrovirus (JSRV) is a unique oncogenic virus with distinctive biological properties. JSRV is the only virus causing a naturally occurring lung cancer (ovine pulmonary adenocarcinoma, OPA) and possessing a major structural protein that functions as a dominant oncoprotein. Lung cancer is the major cause of death among cancer patients. OPA can be an extremely useful animal model in order to identify the cells originating lung adenocarcinoma and to study the early events of pulmonary carcinogenesis. In this study, we demonstrated that lung adenocarcinoma in sheep originates from infection and transformation of proliferating type 2 pneumocytes (termed here lung alveolar proliferating cells, LAPCs). We excluded that OPA originates from a bronchioalveolar stem cell, or from mature post-mitotic type 2 pneumocytes or from either proliferating or non-proliferating Clara cells. We show that young animals possess abundant LAPCs and are highly susceptible to JSRV infection and transformation. On the contrary, healthy adult sheep, which are normally resistant to experimental OPA induction, exhibit a relatively low number of LAPCs and are resistant to JSRV infection of the respiratory epithelium. Importantly, induction of lung injury increased dramatically the number of LAPCs in adult sheep and rendered these animals fully susceptible to JSRV infection and transformation. Furthermore, we show that JSRV preferentially infects actively dividing cell in vitro. Overall, our study provides unique insights into pulmonary biology and carcinogenesis and suggests that JSRV and its host have reached an evolutionary equilibrium in which productive infection (and transformation) can occur only in cells that are scarce for most of the lifespan of the sheep. Our data also indicate that, at least in this model, inflammation can predispose to retroviral infection and cancer

Physiological Costs of Repetitive Courtship Displays in Cockroaches Handicap Locomotor Performance

Courtship displays are typically thought to have evolved via female choice, whereby females select mates based on the characteristics of a display that is expected to honestly reflect some aspect of the male’s quality. Honesty is typically enforced by mechanistic costs and constraints that limit the level at which a display can be performed. It is becoming increasingly apparent that these costs may be energetic costs involved in the production of dynamic, often repetitive displays. A female attending to such a display may thus be assessing the physical fitness of a male as an index of his quality. Such assessment would provide information on his current physical quality as well as his ability to carry out other demanding activities, qualities with which a choosy female should want to provision her offspring. In the current study we use courtship interactions in the Cuban burrowing cockroach, Byrsotria fumigata to directly test whether courtship is associated with a signaler’s performance capacity. Males that had produced courtship displays achieved significantly lower speeds and distances in locomotor trials than non-courting control males. We also found that females mated more readily with males that produced a more vigorous display. Thus, males of this species have developed a strategy where they produce a demanding courtship display, while females choose males based on their ability to produce this display. Courtship displays in many taxa often involve dynamic repetitive actions and as such, signals of stamina in courtship may be more widespread than previously thought

Comparative Genomics Suggests that the Fungal Pathogen Pneumocystis Is an Obligate Parasite Scavenging Amino Acids from Its Host's Lungs

Pneumocystis jirovecii is a fungus causing severe pneumonia in immuno-compromised patients. Progress in understanding its pathogenicity and epidemiology has been hampered by the lack of a long-term in vitro culture method. Obligate parasitism of this pathogen has been suggested on the basis of various features but remains controversial. We analysed the 7.0 Mb draft genome sequence of the closely related species Pneumocystis carinii infecting rats, which is a well established experimental model of the disease. We predicted 8’085 (redundant) peptides and 14.9% of them were mapped onto the KEGG biochemical pathways. The proteome of the closely related yeast Schizosaccharomyces pombe was used as a control for the annotation procedure (4’974 genes, 14.1% mapped). About two thirds of the mapped peptides of each organism (65.7% and 73.2%, respectively) corresponded to crucial enzymes for the basal metabolism and standard cellular processes. However, the proportion of P. carinii genes relative to those of S. pombe was significantly smaller for the “amino acid metabolism” category of pathways than for all other categories taken together (40 versus 114 against 278 versus 427, P<0.002). Importantly, we identified in P. carinii only 2 enzymes specifically dedicated to the synthesis of the 20 standard amino acids. By contrast all the 54 enzymes dedicated to this synthesis reported in the KEGG atlas for S. pombe were detected upon reannotation of S. pombe proteome (2 versus 54 against 278 versus 427, P<0.0001). This finding strongly suggests that species of the genus Pneumocystis are scavenging amino acids from their host's lung environment. Consequently, they would have no form able to live independently from another organism, and these parasites would be obligate in addition to being opportunistic. These findings have implications for the management of patients susceptible to P. jirovecii infection given that the only source of infection would be other humans