Clinical outcomes, not clinical utility, should be the major consideration for saxagliptin with or without metformin

A recent review by Panagoulias and Doupis, published in Patient Preference and Adherence, concerned the saxagliptin/metformin fixed combination (SAXA/MET FDC), and was titled "Clinical utility in the treatment of type 2 diabetes with the saxagliptin/metformin fixed combination."1 This review concluded that "The SAXA/MET FDC is a patient-friendly, dosage-flexible, and hypoglycemia-safe regimen with very few adverse events and a neutral or even favorable effect on body weight. It achieves significant glycosylated hemoglobin A1c reduction helping the patient to achieve his/her individual glycemic goals."1

Facilitating lifestyle changes to manage menopausal symptoms in women with breast cancer: A randomized controlled pilot trial of The Pink Women’s Wellness Program

OBJECTIVE Women diagnosed as having breast cancer may experience difficulties with posttreatment effects such as menopausal symptoms. The aims of this pilot study were to (1) evaluate the impact of a multimodal lifestyle program on reducing menopausal symptoms in women with breast cancer and (2) examine the impact of the program on health-related quality of life (HRQoL) and adherence to lifestyle recommendations. METHODS Overall, 55 women aged 45 to 60 years with one moderate to severe menopausal symptom and a history of breast cancer were randomized into an intervention group (n = 26) or a control group (n = 29). Women in the intervention group received a lifestyle intervention (The Pink Women’s Wellness Program) that included clinical consultations and a tailored health education program. Measurements of menopausal symptoms (Greene Climacteric Scale), HRQoL (SF-12 and Functional Assessment of Cancer Therapy—Breast), and modifiable lifestyle factors (food intake, physical activity, smoking and alcohol use, and sleep disturbance) were taken at baseline and 12 weeks. RESULTS Women in the intervention group reported clinically significant reductions in many menopausal symptoms, specifically somatic symptoms (d = 0.52), vasomotor symptoms (d = 0.55), sexual dysfunction (d = .65), and overall menopausal symptoms (d = 0.54), at 12 weeks compared with the control group (d = 0.03, d = 0.24, d = 0.18, and d = 0.05, respectively). Women in the intervention group reported improvements in Functional Assessment of Cancer Therapy—Breast subscale scores, physical well-being and functional well-being, and Functional Assessment of Cancer Therapy—General total scores (intervention group: d = 0.54, d = 0.50, and d = 0.48, respectively; control group: d = 0.22, d = 0.11, and d = 0.05, respectively). CONCLUSIONS The Pink Women’s Wellness Program is effective in decreasing menopausal symptoms, thus improving HRQoL. This being a pilot study, further research is recommended to investigate the benefits of combining nonpharmacological interventions for women with breast cancer to reduce their treatment-related menopausal symptoms.

Health care consumers’ perspectives on pharmacist integration into private general practitioner clinics in Malaysia: A qualitative study

Background Pharmacists are considered medication experts but are underutilized and exist mainly at the periphery of the Malaysian primary health care team. Private general practitioners (GPs) in Malaysia are granted rights under the Poison Act 1952 to prescribe and dispense medications at their primary care clinics. As most consumers obtain their medications from their GPs, community pharmacists’ involvement in ensuring safe use of medicines is limited. The integration of a pharmacist into private GP clinics has the potential to contribute to quality use of medicines. This study aims to explore health care consumers’ views on the integration of pharmacists within private GP clinics in Malaysia. Methods A purposive sample of health care consumers in Selangor and Kuala Lumpur, Malaysia, were invited to participate in focus groups and semi-structured interviews. Sessions were audio recorded and transcribed verbatim and thematically analyzed using NVivo 10. Results A total of 24 health care consumers participated in two focus groups and six semi-structured interviews. Four major themes were identified: 1) pharmacists’ role viewed mainly as supplying medications, 2) readiness to accept pharmacists in private GP clinics, 3) willingness to pay for pharmacy services, and 4) concerns about GPs’ resistance to pharmacist integration. Consumers felt that a pharmacist integrated into a private GP clinic could offer potential benefits such as to provide trustworthy information on the use and potential side effects of medications and screening for medication misadventure. The potential increase in costs passed on to consumers and GPs’ reluctance were perceived as barriers to integration. Conclusion This study provides insights into consumers’ perspectives on the roles of pharmacists within private GP clinics in Malaysia. Consumers generally supported pharmacist integration into private primary health care clinics. However, for pharmacists to expand their capacity in providing integrated and collaborative primary care services to consumers, barriers to pharmacist integration need to be addressed.

Advance care planning in stroke: Influence of time on engagement in the process

Purpose Individuals who experience stroke have a higher likelihood of subsequent stroke events, making it imperative to plan for future medical care. In the event of a further serious health event, engaging in the process of advanced care planning (ACP) can help family members and health care professionals (HCPs) make medical decisions for individuals who have lost the capacity to do so. Few studies have explored the views and experiences of patients with stroke about discussing their wishes and preferences for future medical events, and the extent to which stroke HCPs engage in conversations around planning for such events. In this study, we sought to understand how the process of ACP unfolded between HCPs and patients post-stroke. Patients and methods Using grounded theory (GT) methodology, we engaged in direct observation of HCP and patient interactions on an acute stroke unit and two stroke rehabilitation units. Using semi-structured interviews, 14 patients and four HCPs were interviewed directly about the ACP process. Results We found that open and continual ACP conversations were not taking place, patients experienced an apparent lack of urgency to engage in ACP, and HCPs were uncomfortable initiating ACP conversations due to the sensitive nature of the topic. Conclusion In this study, we identified lack of engagement in ACP post-stroke, attributable to patient and HCP factors. This encourages us to look further into the process of ACP in order to develop open communication between the patient with stroke, their families, and stroke HCPs.

The effects of compression use during exercise in women with breast cancer-related lymphoedema

Compelling evidence demonstrates the importance of regular exercise following breast cancer, and this is particularly important for those who develop breast cancer-related lymphoedema. However, fear of lymphoedema exacerbation and the need to wear compression while exercising present as significant barriers for these women. This Master's research evaluated the need for wearing compression during exercise in women with breast cancer-related lymphoedema. Findings demonstrated that exercise performed without compression does not exacerbate lymphoedema or related symptoms. These findings are clinically relevant as they highlight that compression use during exercise should be prescribed on an individual basis, taking into consideration patient preferences and adherence issues.

Insurance contract disclosure – an uncertain balance

This article canvasses recent case law adjudicating the uneasy disclosure balance between the interests of the insurer and the insured in the process of transacting an insurance contract. It examines also the consequences of non-disclosure and misrepresentation and whether the avowed legislative intent — that the liability of the insurer in respect of a claim is to be reduced to the amount that would place the insurer in the position it would have been had the non-disclosure or misrepresentation not occurred — is being achieved in practice. As there is no doubt as to who bears the onus of proof as to non-disclosure or misrepresentation it is surprising that insurers continue to flounder in this regard in relation to underwriting guidelines and adherence to them. The article reviews recent case law in this context and stresses that an insurer wishing to preserve its capacity to avoid liability on the basis that it would not have entered into a contract at all had the true situation been known to it must maintain detailed underwriting guidelines supported by consistent adherence to those guidelines. Recent case law also emphasises that the insurer must provide clear and cogent admissible evidence from appropriate personnel and officers of the company to discharge its onus.

Design thinking using a collaborative model for skin cancer prevention

Physical activity is well recognised as a means to reduce cancer risk; however, outdoor activity can increase sun exposure and consequential skin cancer risk. It is proposed, one of the key potential solutions to promote active lifestyles whilst enhancing protection against skin cancer is design resolution for active apparel that considers Australia’s sub-tropical climate whilst maintaining comfort, aesthetic appeal and performance. Using a design thinking approach, facilitated through collaboration between an NGO and a university, student designers were tasked with developing apparel prototypes to explore this challenge. Through practical ideation of problems, potential design solutions were developed within a modest NGO budget and adherence to specific brand guidelines. This project is novel as it demonstrates a low cost yet effective way of collaboratively creating a product to meet multiple needs, rather than reactively assessing already manufactured sun protection products for endorsement. It is a nimble and unique stepping stone in integrating sun safety considerations into clothing that is appealing to the population and creating cross-industry understandings of how design can better contribute to human health and wellbeing. Outcomes to be shared include empirical insights for updating sun safe clothing guidelines, issues around the aesthetic nature of sun safe apparel, and the role of design education for sun safety.

Ei oo kahta samanlaista siskoo: Yksilöllisyys Suomessa asuvien musliminaisten pukeutumisessa

Tutkimuksessa etsittiin vastauksia kysymyksiin, mistä yksilöllisyys muodostuu ja miten se ilmenee musliminaisten pukeutumisessa. Vastauksia tutkimuskysymyksiin haettiin teorian ja aineiston vuoropuheluun perustuvalla fenomenologisesti orientoituneella sisällönanalyysilla. Analysoitava aineisto on hankittu haastattelemalla yhdeksää Suomessa asuvaa musliminaista. Tutkimuksessa yksilöllisyyttä pukeutumisessa on tarkasteltu prosessina. Prosessiin vaikuttavina tekijöinä on tarkasteltu yksilön olemusta, personallisuutta, minuutta, identiteettejä, uskontoa, kulttuuria ja sosiaalisia suhteita. Prosessissa keskeistä aineiston perusteella oli positiivisen minuuden kokemuksen tavoittelu, joka tarkoitti naisille intuitiivista oman itsensä tunnistamista ja tyytyväisyyttä peilin heijastamaan kuvaan. Yksilöllisen pukeutumisen voikin sanoa olevan seurausta positiivisen minuuden kokemuksen tavoittelusta, koska jokaiselle naiselle erilainen pukeutuminen antoi tunteen sopivuudesta itselle. Esimerkiksi uskonnolliselle musliminaisille pään peittäminen merkitsee oman minuuden toteutumista, koska hän kokee tuon pukeutumisen olevan uskon mukainen pukeutumistapa. Toiselle musliminaiselle pään peittäminen voi merkitä positiivisen minuuden kokemuksen menettämistä. Yksilöllisyys pukeutumisessa ilmeni monin tavoin. Osa naisista peittää julkisuudessa koko päänsä ja vartalonsa, osa ei peitä päätään ja jotkut pukeutuvat jopa tiukkoihin tai paljastaviin vaatteisiin. Suomessa on myös kasvonsa peittäviä musliminaisia, joita ei kuitenkaan ole mukana tässä tutkimuksessa. Yksilöllisyyttä ilmeni kuitenkin myös samalla tavalla pukeutuvien musliminaisten ryhmässä. Yksilöllisyys pukeutumisessa ilmeni erilaisina vaatekappaleina, hiustyyleinä, valintoina, yksityiskohtina ja väreinä. Yksilöllisyydessä ei kuitenkaan ole kyse vain havaittavasta pukeutumisen erilaisuudesta, vaan siitä, miten kukin musliminainen kuuluu tähän maailmaan ja toteuttaa omaa minuuttaan pukeutumisella. Tämä tarkoittaa sitä, että tutkimuksessa yksilöllisenä pukeutumisena voidaan pitää sitäkin, mikä monen suomalaisen mielestä ei näytä yksilölliseltä. Avainsanat: Yksilöllisyys, minuus, pukeutuminen, islam, naiset, prosessi, kokemus

Novel conditional mouse models for targeted kidney research : Emphasis on the analysis of the biological function of nephrin

Nephrin is a transmembrane protein belonging to the immunoglobulin superfamily and is expressed primarily in the podocytes, which are highly differentiated epithelial cells needed for primary urine formation in the kidney. Mutations leading to nephrin loss abrogate podocyte morphology, and result in massive protein loss into urine and consequent early death in humans carrying specific mutations in this gene. The disease phenotype is closely replicated in respective mouse models. The purpose of this thesis was to generate novel inducible mouse-lines, which allow targeted gene deletion in a time and tissue-specific manner. A proof of principle model for succesful gene therapy for this disease was generated, which allowed podocyte specific transgene replacement to rescue gene deficient mice from perinatal lethality. Furthermore, the phenotypic consequences of nephrin restoration in the kidney and nephrin deficiency in the testis, brain and pancreas in rescued mice were investigated. A novel podocyte-specific construct was achieved by using standard cloning techniques to provide an inducible tool for in vitro and in vivo gene targeting. Using modified constructs and microinjection procedures two novel transgenic mouse-lines were generated. First, a mouse-line with doxycycline inducible expression of Cre recombinase that allows podocyte-specific gene deletion was generated. Second, a mouse-line with doxycycline inducible expression of rat nephrin, which allows podocyte-specific nephrin over-expression was made. Furthermore, it was possible to rescue nephrin deficient mice from perinatal lethality by cross-breeding them with a mouse-line with inducible rat nephrin expression that restored the missing endogenous nephrin only in the kidney after doxycycline treatment. The rescued mice were smaller, infertile, showed genital malformations and developed distinct histological abnormalities in the kidney with an altered molecular composition of the podocytes. Histological changes were also found in the testis, cerebellum and pancreas. The expression of another molecule with limited tissue expression, densin, was localized to the plasma membranes of Sertoli cells in the testis by immunofluorescence staining. Densin may be an essential adherens junction protein between Sertoli cells and developing germ cells and these junctions share similar protein assembly with kidney podocytes. This single, binary conditional construct serves as a cost- and time-efficient tool to increase the understanding of podocyte-specific key proteins in health and disease. The results verified a tightly controlled inducible podocyte-specific transgene expression in vitro and in vivo as expected. These novel mouse-lines with doxycycline inducible Cre recombinase and with rat nephrin expression will be useful for conditional gene targeting of essential podocyte proteins and to study in detail their functions in the adult mice. This is important for future diagnostic and pharmacologic development platforms.

Bacterial extracellular polysaccharides

Extracellular polysaccharides are as structurally and functionally diverse as the bacteria that synthesise them. They can be present in many forms, including cell-bound capsular polysaccharides, unbound "slime", and as O-antigen component of lipopolysaccharide, with an equally wide range of biological functions. These include resistance to desiccation, protection against nonspecific and specific host immunity, and adherence. Unsurprisingly then, much effort has been made to catalogue the enormous structural complexity of the extracellular polysaccharides made possible by the wide assortment of available monosaccharide combinations, non-carbohydrate residues, and linkage types, and to elucidate their biosynthesis and export. In addition, the work is driven by the commercial potential of these microbial substances in food, pharmaceutics and biomedical industries. Most recently, bacteria-mediated environmental restoration and bioleaching have been attracting much attention owing to their potential to remediate environmental effluents produced by the mining and metallurgy industries. In spite of technological advances in chemistry, molecular biology and imaging techniques that allowed for considerable expansion of knowledge pertaining to the bacterial surface polysaccharides, current understanding of the mechanisms of synthesis and regulation of extracellular polysaccharides is yet to fully explain their structural intricacy and functional variability.

Portrait of Benjamin Liebermann

This large ambitious painting is one of Liebermann's earliest. His uncle, the Geheime Kommerzienrat (Privy Councillor) Benjamin Liebermann (1847-1935), is elderly and slim, but erect and proudly wearing his honorary business medals, has his left hand on his hip, while his right hand rests on the back of a red velvet chair. He is wearing long sideburns and whiskers. The background is plain. The style is tight and painstaking, but already exhibits Liebermann's preference for visible, impasto brushstrokes. The emphasis is on the face, with no attempt at idealization of the akward, but strong features. The colors are mainly black and brown.

Dressing up Tinderella: Interrogating authenticity claims on the mobile dating app Tinder

Mobile dating applications (‘apps’) have increased in popularity over recent years, with Tinder among the first to break into the mainstream heterosexual market. Since mobile dating intensifies the need to confirm that potential dates are not misrepresenting themselves and are safe to meet in person, Tinder’s success indicates that it has allayed these concerns regarding the authenticity of its users. This article combines Giddens’ conceptualization of authenticity, as the ability to reference a coherent biographical narrative, with Callon’s sociology of translation to investigate Tinder’s framing of authenticity within mobile dating. Applying a walkthrough method that interrogates Tinder’s technological architecture, promotional materials, and related media, this hybrid theoretical framework is used to identify how Tinder configures an actor-network that establishes its app as the solution to users’ concerns, enrols individuals in using its features in authenticity claims, and popularizes Tinder’s framing across public discourse. This network of human and non-human actors frames authenticity as being established through one’s Facebook profile and adherence to normative standards relating to age, gender, ethnicity, and socioeconomic status. However, user discourses on other social media identify and challenge negative outcomes of this framing, with normativity fostering discrimination and Facebook verification failing to prevent abusive behavior. This case study of Tinder paves the way for future investigation into user responses to its framing. Further, it demonstrates the efficacy and broader applicability of this theoretical approach for identifying both human and technological influences on the construction of authenticity with digital media.

On the Production of Anorexic Plan Diagrams

A "plan diagram" is a pictorial enumeration of the execution plan choices of a database query optimizer over the relational selectivity space. We have shown recently that, for industrial-strength database engines, these diagrams are often remarkably complex and dense, with a large number of plans covering the space. However, they can often be reduced to much simpler pictures, featuring significantly fewer plans, without materially affecting the query processing quality. Plan reduction has useful implications for the design and usage of query optimizers, including quantifying redundancy in the plan search space, enhancing useability of parametric query optimization, identifying error-resistant and least-expected-cost plans, and minimizing the overheads of multi-plan approaches. We investigate here the plan reduction issue from theoretical, statistical and empirical perspectives. Our analysis shows that optimal plan reduction, w.r.t. minimizing the number of plans, is an NP-hard problem in general, and remains so even for a storage-constrained variant. We then present a greedy reduction algorithm with tight and optimal performance guarantees, whose complexity scales linearly with the number of plans in the diagram for a given resolution. Next, we devise fast estimators for locating the best tradeoff between the reduction in plan cardinality and the impact on query processing quality. Finally, extensive experimentation with a suite of multi-dimensional TPCH-based query templates on industrial-strength optimizers demonstrates that complex plan diagrams easily reduce to "anorexic" (small absolute number of plans) levels incurring only marginal increases in the estimated query processing costs.

Impact of depressive symptoms on subjective well-being: the importance of patient-reported outcomes in schizophrenia

Objective: The subjective experience of psychotic patients toward treatment is a key factor in medication adherence, quality of life, and clinical outcome. The aim of this study was to assess the subjective well-being in patients with schizophrenia and to examine its relationship with the presence and severity of depressive symptoms. Methods: A multicenter, cross-sectional study was conducted with clinically stable outpatients diagnosed with schizophrenia. The Subjective Well-Being under Neuroleptic Scale - short version (SWN-K) and the Calgary Depression Scale for Schizophrenia (CDSS) were used to gather information on well-being and the presence and severity of depressive symptoms, respectively. Spearman's rank correlation was used to assess the associations between the SWN-K total score, its five subscales, and the CDSS total score. Discriminative validity was evaluated against that criterion by analysing the area under the curve (AUC). Results: Ninety-seven patients were included in the study. Mean age was 35 years (standard deviation = 10) and 72% were male. Both the total SWN-K scale and its five subscales correlated inversely and significantly with the CDSS total score (P < 0.0001). The highest correlation was observed for the total SWN-K (Spearman's rank order correlation [ rho] = -0.59), being the other correlations: mental functioning (-0.47), social integration (-0.46), emotional regulation (-0.51), physical functioning (-0.48), and self-control (-0.41). A total of 33 patients (34%) were classified as depressed. Total SWN-K showed the highest AUC when discriminating between depressive severity levels (0.84), followed by emotional regulation (0.80), social integration (0.78), physical functioning and self-control (0.77), and mental functioning (0.73). Total SWN-K and its five subscales showed a significant linear trend against CDSS severity levels (P < 0.001). Conclusion: The presence of moderate to severe depressive symptoms was relatively high, and correlated inversely with patients' subjective well-being. Routine assessment of patient-reported measures in patients with schizophrenia might reduce potential discrepancy between patient and physician assessment, increase therapeutic alliance, and improve outcome.