The association of mood disorders with breast cancer survival: an investigation of linked cancer registration and hospital admission data for South East England.

BACKGROUND: Data linkage studies find that depression before or after a breast cancer diagnosis predicts reduced survival. This study aimed to determine whether depression or bipolar recorded in routine hospital admission data independently predicts survival in English breast cancer patients and whether onset in relation to cancer diagnosis is significant. METHODS: Data on 77,173 women diagnosed with breast cancer (ICD-10 C50) in South East England, 2000-2009, were included. Of these, 131 women had a diagnosis of bipolar affective disorder (ICD-10 F31) and 955 of depression (either depressive episodes (ICD-10 F32) or depressive disorder (ICD-10 F33)) recorded in Hospital Episode Statistics between 3 years before and a year following cancer diagnosis. Kaplan-Meier plots were used to examine overall survival. Cox regression analyses were carried out overall and separately for mood disorder diagnoses before and after the cancer diagnosis and adjusted for confounding variables. RESULTS: A record of depression was a predictor of worse overall survival in breast cancer patients (adjusted HR = 1.33, 95% CI: 1.20-1.48, p < 0.001), while the effect of bipolar was not statistically significant (adjusted HR = 1.33, 95% CI: 0.97-1.82, p = 0.079). New recordings of depression and bipolar diagnoses following a cancer diagnosis appeared better predictors of overall survival than a prior history of either. CONCLUSIONS: There is evidence that English breast cancer patients with depression and bipolar recorded in routine hospital data have worse overall survival than those without these mood disorders. Further work exploring the concordance of records within administrative health data with clinical diagnosis and cause-specific death within these patient groups is needed.

Assessing the Unterberger test: introduction of a novel smartphone application.

BACKGROUND: Peripheral vestibular function is commonly assessed using the Unterberger test. Patients are asked to march on the spot and their extent of rotation is recorded. The sensitivity of this test depends on an assessor accurately estimating the degree of rotation. This study therefore aimed to compare observer estimates with a smartphone application (DplusR Balance) that accurately records rotation. METHOD: Twenty-five participants were asked to estimate the degree of rotation in 10 successive Unterberger tests performed by a volunteer. RESULTS: The average difference between estimated and application recorded extent of rotation was 30°. CONCLUSION: Assessors poorly estimate the degree of rotation in this clinical test, to an extent sufficient to affect clinical interpretation and diagnosis. We recommend the use of this application or alternative methods to record the degree of rotation in patients.

Desarrollo y caracterización de comprimidos bucodispersables de antibiótico / Development and characterization of antibiotic orodispersible tablets

The goal of this project is to formulate oro-dispersible tablet of Azithromycin that is intended to disintegrate rapidly into the oral cavity and form a stabilized dispersion. A direct compression method was failed to formulate dispersible tablet of Azithromycin so wet granulation method was used. In preliminary study different superdisintegrant croscarmellose sodium (CCS), sodium starch glycolate (SSG) and crospovidone (CPVP) were evaluated for weight variation, content uniformity, hardness, disintegration time, and friability of tablets. In all the formulations water was used as a binding agent to attain hardness. Avicel was used as diluents. Aspartame was used as a sweetening agent. Magnesium stearate and Aerosil were used as lubricant and glidant respectively. FT-IR studies were utilized to obtain the compatibility of the drug and excipients. The simplex lattice design was utilized using amount of intragranular concentration of superdisintegrants, sodium starch glycolate(A), cros-carmellose sodium(B) and crospovidone(C) were selected as independent variable. The Hardness (R1), Disintegration time (R2), Friability (R3) and Wetting time (R4) were selected as dependent variables. A total of 11 formulations with 4 replicas was obtained and optimized. From response surface plot of disintegration time, wetting time, friability and hardness it was found that lower disintegration time of tablets could be obtained when C and B are kept at optimum level. Stability study of final batch showed no significant changes in tablet properties(AU)

El objetivo de este proyecto es la formulación de comprimidos bucodispersables de azitromicina que se desintegren rápidamente en la cavidad bucal y formen una dispersión estable. La formulación de comprimidos dispersables de azitromicina no se pudo realizar con el método de compresión directo, por lo que se usó el método de granulación húmeda. En un estudio preliminar, se evaluó el efecto de diferentes superdisgregantes, como croscarmelosa de sodio (CSS), glicolato sódico de almidón (SSG) y crospovidona, en la variación de peso, uniformidad, dureza, tiempo de disgregación y friabilidad de los comprimidos. En todas las formulaciones, se usó agua como agente aglutinante para conseguir dureza. Se usó Avicel como agente disolvente y aspartamo como agente edulcorante. Estearato de magnesio y Aerosil se usaron como lubricante y deslizante, respectivamente. Se usaron estudios FT-IR para obtener la compatibilidad de los fármacos y los excipientes. El diseño de celosía simple se aplicó usando distintas cantidades de concentraciones intragranulares de superdisgregantes. Se seleccionaron, como variables independientes, el glicolato sódico de almidón (A), la croscarmelosa de sodio (B) y la crospovidona (C). Como variables dependientes, se eligieron la dureza (R1), el tiempo de desintegración (R2), la friabilidad (R3) y el tiempo de humectación (R4). Se obtuvieron y se optimizaron un total de 11 formulaciones con 4 réplicas. Según la gráfica de la superficie de respuesta del tiempo de disgregación, el tiempo de humectación, la friabilidad y la dureza, se observó que se podía obtener un tiempo de disgregación más bajo cuando C y B se mantenían en un nivel óptimo. El estudio de estabilidad del último grupo no mostró cambios significativos en las propiedades de los comprimidos(AU)

Interventions for helping patients to follow prescriptions for medications.

BACKGROUND: Efforts to assist patients with adherence to prescribed, self-administered medications might improve the benefits and efficiency of health care. OBJECTIVE: To update an ongoing review summarising the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications, focusing on trials that measured both adherence and clinical outcomes. SEARCH STRATEGY: Computerised searches to July 1998 in MEDLINE, CINAHL, The Cochrane Library, International Pharmaceutical Abstracts (IPA), PsychInfo, Sociofile, and HSTAR; bibliographies in articles on patient adherence; articles in the reviewers' personal collections; and contact with authors. SELECTION CRITERIA: Articles were selected if they reported an unconfounded RCT of an intervention to improve adherence with prescribed medications, measuring both medication adherence and treatment outcome, with at least 80% follow-up of each group studied and, for long-term treatments, at least six months follow-up for studies with positive initial findings. DATA COLLECTION AND ANALYSIS: Information on study design features, interventions and controls, and findings were extracted by one reviewer (PM) and a research assistant and confirmed by two of the other reviewers. The studies were too disparate to warrant meta-analysis. MAIN RESULTS: For short-term treatments, one study, of counselling and written information, showed an effect on adherence and clinical outcome. Ten of 19 interventions for long-term treatments reported in 17 RCTs were associated with improvements in adherence, but only nine interventions led to improvements in treatment outcomes. Almost all of the interventions that were effective for long-term care were complex, including combinations of more convenient care, information, counselling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions did not lead to large improvements in adherence and treatment outcomes. Two studies showed that telling patients about adverse effects of treatment did not affect their adherence. REVIEWER'S CONCLUSIONS: The full benefits of medications cannot be realised at currently achievable levels of adherence. Current methods of improving adherence for chronic health problems are mostly complex and not very effective. More studies of innovative approaches to assist patients to follow medication prescriptions are needed.

Regulation of the Na,K-pump by leptin in 3T3-L1 fibroblasts.

Leptin, the product of the obesity (ob) gene, controls energy intake and expenditure primarily by actions on the central nervous system. However, recently it has become apparent that leptin also elicits a growing and diverse array of effects on peripheral tissues. The Na,K-pump is an electrogenic plasma membrane protein which actively extrudes 3Na+ ions and imports 2K+ ions per molecule of ATP hydrolysed. The pump is responsible for the maintenance of the electrochemical potential of all cells, which in turn drives all ion-coupled transport mechanisms. In this study we use 3T3-L1 fibroblasts to show that leptin inhibits Na,K-pump activity, as assessed by ouabain-sensitive 86Rb+ uptake. Inhibition of the Na,K-pump correlated with increased serine phosphorylation of the catalytic Na,K-pump alpha1 subunit. Upon investigation of leptin-stimulated signalling pathways using specific pharmacological inhibitors, only wortmannin prevented inhibition of the Na,K-pump by leptin. Moreover, leptin stimulated phosphotyrosine-associated PI 3-kinase activity in these cells. In summary, leptin was found to inhibit Na,K-pump activity, likely via PI 3-kinase. We propose that this effect may have wide ranging cardiovascular and metabolic implications and perhaps explain physiological effects of the hormone such as natriuresis.

Systematic review of randomised trials of interventions to assist patients to follow prescriptions for medications.

BACKGROUND: Low adherence of patients to prescribed, self-administered medical interventions is ubiquitous. Low adherence limits the benefits of current medical care. Efforts to assist patients to follow treatments might improve the efficiency of care and substantially enhance benefits. Our objective was to summarise the results of randomised controlled trials (RCTs) of interventions to help patients follow prescriptions for medications. METHODS: A previous systematic review was updated through computerised searches in Medline, International Pharmaceutical Abstracts, Psychinfo, and HSTAR online databases; bibliographies in articles on patient adherence; articles in the reviewers' personal collections; and contact with authors. Articles were judged of interest if they reported original data concerning an unconfounded RCT of an intervention to improve adherence with prescribed medications, with one or more measure of medication adherence, one or more measure of treatment outcome, at least 80% follow-up of each group studied, and, for long-term treatments, at least 6 months of follow-up for studies with positive initial findings. Information on study design features, interventions and controls, and findings were extracted by one reviewer (RK) and checked by the other two reviewers. FINDINGS: 1,553 relevant citations and abstracts were screened, 252 full text articles were reviewed in detail, and 13 RCTs met all criteria. The studies were too disparate in clinical problems, adherence interventions, measures and reporting of adherence, and the clinical outcomes studied to warrant meta-analysis. Seven of 15 interventions were associated with improvements in adherence and six interventions led to improvements in treatment outcomes. For short-term treatments, one study showed an effect on adherence and outcome of counselling and written information. The interventions that were effective for long-term care were complex, including various combinations of more convenient care, information, counselling, reminders, self-monitoring, reinforcement, family therapy, and other forms of additional supervision or attention. Even the most effective interventions did not lead to substantial improvements in adherence. INTERPRETATION: Although adherence and treatment outcomes can be improved by certain-usually complex-interventions, full benefits of medications cannot be realised at currently achievable levels of adherence. It is time that additional efforts be directed towards developing and testing innovative approaches to assist patients to follow treatment prescriptions.