Medication adherence among patients with advanced prostate cancer using oral therapies.

Aims: In light of the extended overall survival and improved quality of life provided by advanced prostate cancer (PC) oral therapies, this study aimed to describe treatment adherence to advanced PC oral therapies and evaluate associated patient characteristics and subsequent healthcare resource utilization (HRU). Patients & methods: Patients with advanced PC initiating apalutamide, enzalutamide or abiraterone acetate were identified from administrative data (October 1, 2014-September 30, 2019). Adherence and persistence at six months postinitiation were used to evaluate patient factors and HRU. Results: Aged ≥75 years, Black race, chemotherapy use and higher pharmacy paid amounts were associated with poor adherence/persistence, which translated to higher HRU. Conclusions: Strategies to increase adherence and persistence may improve patient outcomes and associated HRU.

Lay abstract This study included 27,262 patients with advanced prostate cancer who started taking one of three oral cancer medications (apalutamide, enzalutamide or abiraterone acetate) between October 2014 and September 2019. Patients who were black, aged 75 years or older, who had chemotherapy or who had higher prescription costs had the most difficulty following dosing guidelines or staying on treatment. Patients who did not follow dosing guidelines required more healthcare services. In light of the extended survival and improved quality of life that oral cancer medication for advanced prostate cancer provides, helping patients to take the correct medication dose, at the right time, and for the recommended length of time may improve their outcomes and reduce medical costs.

ENZA-p trial protocol: a randomized phase II trial using prostate-specific membrane antigen as a therapeutic target and prognostic indicator in men with metastatic castration-resistant prostate cancer treated with enzalutamide (ANZUP 1901).

OBJECTIVES: To determine the activity and safety of lutetium-177 (177 Lu)-prostate-specific membrane antigen (PSMA)-617 in men with metastatic castration-resistant prostate cancer (mCRPC) commencing enzalutamide, who are at high risk of early progression, and to identify potential prognostic and predictive biomarkers from imaging, blood and tissue. PARTICIPANTS AND METHODS: ENZA-p (ANZUP 1901) is an open-label, randomized, two-arm, multicentre, phase 2 trial. Participants are randomly assigned (1:1) to treatment with enzalutamide 160 mg daily alone or enzalutamide plus 177 Lu-PSMA-617 7.5 GBq on Days 15 and 57. Two additional 177 Lu-PSMA-617 doses are allowed, informed by Day-92 Gallium-68 (68 Ga)-PSMA positron emission tomography (PET; up to four doses in total). The primary endpoint is prostate-specific antigen (PSA) progression-free survival (PFS). Other major endpoints include radiological PFS, PSA response rate, overall survival, health-related quality of life, adverse events and cost-effectiveness. Key eligibility criteria include: biochemical and/or clinical progression; 68 Ga-PSMA PET-avid disease; no prior androgen signalling inhibitor, excepting abiraterone; no prior chemotherapy for mCRPC; and ≥2 high-risk features for early enzalutamide failure. Assessments are 4 weekly during study treatment, then 6 weekly until radiographic progression. Response Evaluation Criteria in Solid Tumours (RECIST) are used to assess imaging conducted every 12 weeks, 68 Ga-PSMA PET at baseline, Days 15 and 92, and at progression, and 18 F-fluorine deoxyglucose (18 F-FDG) PET at baseline and progression. Translational samples include blood (and optional biopsies) at baseline, Day 92, and first progression. Correlative studies include identification of prognostic and predictive biomarkers from 68 Ga-PSMA and 18 F-FDG PET/CT, circulating tumour cells and circulating tumour DNA. The trial will enrol 160 participants, providing 80% power with a two-sided type-1 error rate of 5% to detect a hazard ratio of 0.625 assuming a median PSA-PFS of 5 months with enzalutamide alone. RESULTS AND CONCLUSION: The combination of 177 Lu-PSMA-617 and enzalutamide may be synergistic. ENZA-p will determine the safety and efficacy of the combination in addition to developing predictive and prognostic biomarkers to better guide treatment decisions.

Assessment of cochlear toxicity in response to chronic 3,3'-iminodipropionitrile in mice reveals early and reversible functional loss that precedes overt histopathology.

The peripheral auditory and vestibular systems rely on sensorineural structures that are vulnerable to ototoxic agents that cause hearing loss and/or equilibrium deficits. Although attention has focused on hair cell loss as the primary pathology underlying ototoxicity, evidence from the peripheral vestibular system indicates that hair cell loss during chronic exposure is preceded by synaptic uncoupling from the neurons and is potentially reversible. To determine if synaptic pathology also occurs in the peripheral auditory system, we examined the extent, time course, and reversibility of functional and morphological alterations in cochleae from mice exposed to 3,3'-iminodipropionitrile (IDPN) in drinking water for 2, 4 or 6 weeks. Functionally, IDPN exposure caused progressive high- to low-frequency hearing loss assessed by measurement of auditory brainstem response wave I absolute thresholds and amplitudes. The extent of hearing loss scaled with the magnitude of vestibular dysfunction assessed behaviorally. Morphologically, IDPN exposure caused progressive loss of outer hair cells (OHCs) and synapses between the inner hair cells (IHCs) and primary auditory neurons. In contrast, IHCs were spared from ototoxic damage. Importantly, hearing loss consistent with cochlear synaptopathy preceded loss of OHCs and synapses and, moreover, recovered if IDPN exposure was stopped before morphological pathology occurred. Our observations suggest that synaptic uncoupling, perhaps as an early phase of cochlear synaptopathy, also occurs in the peripheral auditory system in response to IDPN exposure. These findings identify novel mechanisms that contribute to the earliest stages of hearing loss in response to ototoxic agents and possibly other forms of acquired hearing loss.

Principal-agent theory-based cost and reimbursement structures of isavuconazole treatment in German hospitals.

BACKGROUND: Isavuconazole (ISA) is a frequently used antifungal agent for the treatment of invasive fungal diseases (IFDs). However, hospital reimbursement data for ISA is limited. OBJECTIVES: The primary objective of this study was to analyse the different perspectives of relevant stakeholders and the (dis)incentives for the administration of ISA in Germany. To that aim, the health economic effects of using ISA from a hospital management perspective were analysed. PATIENTS/METHODS: Based on principal-agent theory (PAT), the perspectives of (a) the patient (principal) as well as (b) physicians, (c) pharmacists and iv. hospital managers (all agents) were analysed. For the evaluation of the cost-containment and reimbursement strategies of ISA, the German diagnosis-related group (G-DRG) system was used. RESULTS: Hospitals individually negotiating additional payments for innovative treatment procedures (zusatzentgelte [ZE]) within the G-DRG system is a key element of hospital management for the reduction of total healthcare expenditure. Our analysis demonstrated the beneficial role of ISA in healthcare resource utilisation, primarily due to a shortened overall length of hospital stay. Depending on underlying disease, coded G-DRG and ISA formulation, large differences in total reimbursement and the amount of ZE was shown. The PAT demonstrated disincentives for hospital managers to use innovative drugs. CONCLUSIONS: Based on the PAT, beneficial, detrimental and indifferent perspectives of different stakeholders regarding the usage of ISA were shown. A reduction of bureaucratic hurdles is needed in Germany for the extension of effective and innovative antifungal treatment strategies with ISA.

Adherence and out-of-pocket costs among Medicare beneficiaries who are prescribed oral targeted therapies for advanced prostate cancer.

BACKGROUND: Abiraterone and enzalutamide are high-cost oral therapies that increasingly are used to treat patients with advanced prostate cancer; these agents carry the potential for significant financial consequences to patients. In the current study, the authors investigated coping and material measures of the financial hardship of these therapies among patients with Medicare Part D coverage. METHODS: The authors performed a retrospective cohort study on a 20% sample of Medicare Part D enrollees who underwent treatment with abiraterone or enzalutamide between July 2013 and June 2015. The authors described the variability in adherence rates and out-of-pocket payments among hospital referral regions in the first 6 months of therapy and determined whether adherence and out-of-pocket payments were associated with patient factors and the socioeconomic characteristics of where a patient was treated. RESULTS: There were 4153 patients who filled abiraterone or enzalutamide prescriptions through Medicare Part D in 228 hospital referral regions. The mean adherence rate was 75%. The median monthly out-of-pocket payment for abiraterone and enzalutamide was $706 (range, $0-$3505). After multilevel, multivariable adjustment for patient and regional factors, adherence was found to be lower in patients who were older (69% for patients aged ≥85 years vs 76% for patients aged <70 years; P < .01) and in those with low-income subsidies (69% in those with a subsidy vs 76% in those without a subsidy; P < .01). Both Hispanic ethnicity and living in a hospital referral region with a higher percentage of Hispanic beneficiaries were found to be independently associated with higher out-of-pocket payments for abiraterone and enzalutamide. CONCLUSIONS: There were substantial variations in the adherence rate and out-of-pocket payments among Medicare Part D beneficiaries who were prescribed abiraterone and enzalutamide. Sociodemographic patient and regional factors were found to be associated with both adherence and out-of-pocket payments.

Isavuconazole to prevent invasive fungal infection in immunocompromised adults: Initial experience at an academic medical centre.

OBJECTIVE: To evaluate clinical and economic outcomes associated with the use of isavuconazole as antifungal prophylaxis in high-risk immunocompromised patients. PATIENTS/METHODS: Retrospective, single-centre cohort study of patients who received isavuconazole prophylaxis. Outcomes assessed included breakthrough IFI, early discontinuation of isavuconazole for any reason and antifungal prophylaxis prescribed at discharge. The impact on inpatient drug expenditure was evaluated using current isavuconazole and posaconazole drug costs per observed isavuconazole days of therapy (DOT) during the study period. RESULTS: One hundred thirty-eight courses of isavuconazole prophylaxis were administered to 98 inpatients (2193 DOT). Relapsed/refractory acute myelogenous leukaemia was the indication for prophylaxis in over half (59.4%) of patients. Breakthrough IFI occurred in 8 (5.8%) courses. Suspected drug-related toxicities led to early discontinuation in 6 (4.3%) courses (five hepatotoxicity, one drug rash). At discharge, 24 (17.4%) courses lacked insurance coverage for isavuconazole. The formulary switch to isavuconazole prophylaxis resulted in an estimated mean drug cost savings of $128.25 per DOT relative to estimated posaconazole costs (P < 0.001). CONCLUSION: Isavuconazole may be an option for antifungal prophylaxis in high-risk immunocompromised adults and has the potential to produce significant inpatient drug cost savings. Further studies are needed to confirm the clinical efficacy and cost-effectiveness of isavuconazole in this role.

Assessment of ethylene glycol diacetate as an alternative carrier for use in agrochemical emulsifiable concentrate formulation.

The conventional emulsifiable concentrate (EC) formulation contains a large amount of aromatic solvents, which causes adverse effects to both the environment and human health due to the toxicity of the solvents. Here, we developed a 2.5% lambda-cyhalothrin EC formulation with ethylene glycol diacetate (EGDA) as the solvent, and the developed formulation serves as an environmental-friendly alternative to overcome the adverse effects of aromatic solvents. The physicochemical characterizations, wettability properties, phytotoxicity and bioassays of the EGDA-EC formulation were systematically investigated and compared with that of the EC formulation with xylene as the solvent. The results showed that both EC formulations had excellent emulsion properties and storage stabilities. Additionally, the EGDA-EC formulation possessed a higher flash point (96 °C), indicating safer production, storage and transport. The retentions of the EGDA-EC sample on leaves were 1.22-1.46-fold higher than that of the xylene-EC sample, and the EGDA-EC also exhibited lower surface tensions and contact angles, which would benefit decreasing drift-off and improving utilization. Furthermore, the bioassays demonstrated that the EGDA-EC formulation had lower acute toxicity to aquatic organisms and higher control efficacy to target insects compared with the xylene-EC formulation. Therefore, EGDA is a promising carrier for oil-soluble agrochemicals to improve their application performance and reduce their adverse effects.

Patterns of Bicalutamide Use in Prostate Cancer Treatment: A U.S. Real-World Analysis Using the SEER-Medicare Database.

INTRODUCTION: Bicalutamide (BIC), a non-steroidal anti-androgen, is FDA-indicated for use in combination with a luteinizing hormone-releasing hormone (LHRH) analog for treatment of Stage D2 metastatic carcinoma of the prostate. Lack of consensus exists regarding the clinical benefit of BIC use, either alone or combined use of BIC with an LHRH analog or antagonist (combined androgen blockade or CAB), versus treatment with androgen deprivation therapy (ADT) alone. METHODS: The SEER-Medicare database was used to identify prostate cancer patients aged ≥ 66 years diagnosed between 2007 and 2011 and who filled at least one prescription for BIC. Duration of BIC treatment was assessed in relation to ADT use; either alone (monotherapy), as part of CAB only, and as part of CAB followed by monotherapy. Additionally, we assessed use of BIC during or outside a potential testosterone flare prevention period (initiation within 2 months of an LHRH agonist). RESULTS: A total of 7521 prostate cancer patients who filled a prescription for BIC were identified. Eighteen percent of the cohort used BIC alone, over half the patients (54%) used BIC as part of CAB and 27% used BIC as part of CAB followed by monotherapy. Among men treated with BIC as part of CAB, 58% received BIC only within the potential flare period. CONCLUSIONS: Although there is no FDA indication for BIC use as monotherapy, > 44% of patients in this study used BIC alone or as part of CAB followed by monotherapy. Further research is necessary to understand the outcomes of BIC utilization in these settings, particularly compared with newer second-generation anti-androgens. FUNDING: Medivation LLC, a Pfizer company, and Astellas, Pharma, Inc.

Assessment of 8-hydroxy-2-deoxyguanosine activity, gene expression and antioxidant enzyme activity on rainbow trout (Oncorhynchus mykiss) tissues exposed to biopesticide.

The goal of this study was to determinate toxicity mechanism of biopesticide with antioxidant enzymes parameters such as superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) and malondialdehyde (MDA) levels, oxidative DNA damage (8-hydroxy-2-deoxyguanosine (8-OHdG)), transcriptional changes of heat shock protein 70 (HSP70), and cytochromes P4501A (CYP1A), sod, cat, and gpx in liver and gill tissues of Oncorhynchus mykiss. For this aim, plant-based (natural pesticides, azadirachtin (AZA)) and synthetic pesticides (deltamethrin (DLM)) were exposed on the fish at different concentrations (0.0005 and 0.00025ppm of DLM; 0.24 and 0.12ppm of AZA) for 21 days. According to the results of the study, the activity of SOD, CAT and GPx decreased, but malondialdehyde (MDA) level and activity of 8-OHdG increased in the gill and liver of rainbow trout (p<0.05). Additionally sod, cat and gpx were down regulated; HSP70 and CYP1A were up regulated for transcriptional observation. The downwards regulation of antioxidant (sod, cat and gpx) and the upregulation of HSP70 and CYP1A was obvious with doses of AZA or DLM (p<0.05). The findings of this study suggest that biopesticide can cause biochemical and physiological effects in the fish gill and liver by causing enzyme inhibition, an increase in 8-OHdG levels and changes in both transcriptional parameters (sod, cat, gpx, HSP70 and CYP1A). We found that excessive doses of plant-based pesticide are nearly as toxic as chemical ones for aquatic organisms. Moreover, 8-OHdG, HSP70 and CYP1A used as a biomarker to determinate toxicity mechanism of biopesticide in aquatic environment.

Prospective assessment of patient-reported outcomes and estradiol and drug concentrations in patients experiencing toxicity from adjuvant aromatase inhibitors.

PURPOSE: Aromatase inhibitors (AI), which decrease circulating estradiol concentrations in post-menopausal women, are associated with toxicities that limit adherence. Approximately one-third of patients will tolerate a different AI after not tolerating the first. We report the effect of crossover from exemestane to letrozole or vice versa on patient-reported outcomes (PROs) and whether the success of crossover is due to lack of estrogen suppression. METHODS: Post-menopausal women enrolled on a prospective trial initiating AI therapy for early-stage breast cancer were randomized to exemestane or letrozole. Those that discontinued for intolerance were offered protocol-directed crossover to the other AI after a washout period. Changes in PROs, including pain [Visual Analog Scale (VAS)] and functional status [Health Assessment Questionnaire (HAQ)], were compared after 3 months on the first versus the second AI. Estradiol and drug concentrations were measured. RESULTS: Eighty-three patients participated in the crossover protocol, of whom 91.3% reported improvement in symptoms prior to starting the second AI. Functional status worsened less after 3 months with the second AI (HAQ mean change AI #1: 0.2 [SD 0.41] vs. AI #2: -0.05 [SD 0.36]; p = 0.001); change in pain scores was similar between the first and second AI (VAS mean change AI #1: 0.8 [SD 2.7] vs. AI #2: -0.2 [SD 2.8]; p = 0.19). No statistical differences in estradiol or drug concentrations were found between those that continued or discontinued AI after crossover. CONCLUSIONS: Although all AIs act via the same mechanism, a subset of patients intolerant to one AI report improved PROs with a different one. The mechanism of this tolerance remains unknown, but does not appear to be due to non-adherence to, or insufficient estrogen suppression by, the second AI.

Liver Resection for Breast Cancer Liver Metastases: A Cost-utility Analysis.

OBJECTIVE: To estimate the cost-effectiveness of liver resection followed by adjuvant systemic therapy relative to systemic therapy alone for patients with breast cancer liver metastasis. BACKGROUND: Data on cost-effectiveness of liver resection for advanced breast cancer with liver metastasis are lacking. METHODS: A decision-analytic Markov model was constructed to evaluate the cost-effectiveness of liver resection followed by postoperative conventional systemic therapy (strategy A) versus conventional therapy alone (strategy B) versus newer targeted therapy alone (strategy C). The implications of using different chemotherapeutic regimens based on estrogen receptor and human epidermal growth factor receptor 2 status was also assessed. Outcomes included quality-adjusted life months (QALMs), incremental cost-effectiveness ratio, and net health benefit (NHB). RESULTS: NHB of strategy A was 10.9 QALMs compared with strategy B when letrozole was used as systemic therapy, whereas it was only 0.3 QALMs when docetaxel + trastuzumab was used as a systemic therapy. The addition of newer biological agents (strategy C) significantly decreased the cost-effectiveness of strategy B (conventional systemic therapy alone). The NHB of strategy A was 31.6 QALMs versus strategy C when palbociclib was included in strategy C; similarly, strategy A had a NHB of 13.8 QALMs versus strategy C when pertuzumab was included in strategy C. Monte-Carlo simulation demonstrated that the main factor influencing NHB of strategy A over strategy C was the cost of systemic therapy. CONCLUSIONS: Liver resection in patients with breast cancer liver metastasis proved to be cost-effective when compared with systemic therapy alone, particularly in estrogen receptor-positive tumors or when newer agents were used.

Pharmacokinetic Assessment of Drug-Drug Interactions of Isavuconazole With the Immunosuppressants Cyclosporine, Mycophenolic Acid, Prednisolone, Sirolimus, and Tacrolimus in Healthy Adults.

This report summarizes phase 1 studies that evaluated pharmacokinetic interactions between the novel triazole antifungal agent isavuconazole and the immunosuppressants cyclosporine, mycophenolic acid, prednisolone, sirolimus, and tacrolimus in healthy adults. Healthy subjects received single oral doses of cyclosporine (300 mg; n = 24), mycophenolate mofetil (1000 mg; n = 24), prednisone (20 mg; n = 21), sirolimus (2 mg; n = 22), and tacrolimus (5 mg; n = 24) in the presence and absence of clinical doses of oral isavuconazole (200 mg 3 times daily for 2 days; 200 mg once daily thereafter). Coadministration with isavuconazole increased the area under the concentration-time curves (AUC0-∞ ) of tacrolimus, sirolimus, and cyclosporine by 125%, 84%, and 29%, respectively, and the AUCs of mycophenolic acid and prednisolone by 35% and 8%, respectively. Maximum concentrations (Cmax ) of tacrolimus, sirolimus, and cyclosporine were 42%, 65%, and 6% higher, respectively; Cmax of mycophenolic acid and prednisolone were 11% and 4% lower, respectively. Isavuconazole pharmacokinetics were mostly unaffected by the immunosuppressants. Two subjects experienced elevated creatinine levels in the cyclosporine study; most adverse events were not considered to be of clinical concern. These results indicate that isavuconazole is an inhibitor of cyclosporine, mycophenolic acid, sirolimus, and tacrolimus metabolism.

Cost effectiveness of letrozole and purified urinary FSH in treating women with clomiphene citrate-resistant polycystic ovarian syndrome: a randomized controlled trial.

We aimed to compare the cost effectiveness of letrozole versus purified urinary follicle stimulating hormone (FSH) in treating patients with clomiphene citrate (CC)-resistant polycystic ovary syndrome (PCOS). This was a randomized trial conducted in Cairo University and Beni-Suef University Hospitals, Egypt. A cohort of 140 eligible women was randomized to receive either letrozole 2.5 mg twice daily for five days, or FSH using a graduated regimen starting with a dose of 75 IU. Treatment was repeated for three months if pregnancy did not occur. There were no significant differences between the two treatments in the cumulative clinical pregnancy rate (30% vs. 34%; p = 0.578), cumulative ovulation rate (47% vs. 57%; p = 0.236), miscarriage rate (9% vs. 4%, p > 0.999) or multiple pregnancy rate (0% and 8%, p = 0.491) but the FSH cycles were 4.8 times more expensive. Letrozole and FSH were both effective in treating women with CC-resistant PCOS but letrozole was more cost effective.Study registration number: NCT02304107.

Pharmacodynamics of isavuconazole in experimental invasive pulmonary aspergillosis: implications for clinical breakpoints.

OBJECTIVES: Isavuconazole, a novel triazole antifungal agent, has broad-spectrum activity against Aspergillus spp. and other pathogenic fungi. The isavuconazole exposure-response relationship in experimental invasive pulmonary aspergillosis using galactomannan index (GMI) suppression as a marker of disease clearance was explored. METHODS: The impact of exposure on GMI suppression in persistently neutropenic rabbits treated with isavuconazonium sulphate (isavuconazole-equivalent dosages of 20, 40 or 60 mg/kg every 24 h, after a 90 mg/kg loading dose) for 12 days was linked using mathematical modelling. Bridging to humans using population pharmacokinetic (PK) data from a clinical trial in invasive aspergillosis was performed using Monte Carlo simulations. RESULTS: Mean plasma isavuconazole AUC/MIC (EC50) of 79.65 (95% CI 32.2, 127.1) produced a half-maximal effect in GMI suppression. The inhibitory sigmoid Emax curve dropped sharply after an AUC/MIC of ≥30 and was near maximum (EC80) at ∼130. Bridging the experimental PK/pharmacodynamic (PD) target to human population PK data was then used to return to the rabbit model to determine a clinically relevant PD endpoint. The clinical dosing regimen used in the trial would result in a mean GMI of 4.3 ±â€Š1.8, which is a 50% reduction from the starting GMI in the experiment. CONCLUSIONS: The clinical trial results showing the non-inferiority of isavuconazole to voriconazole for all-cause mortality further support the PK-PD endpoint, thereby demonstrating the usefulness of the rabbit model and endpoint for isavuconazole and implications on interpretive breakpoints. Importantly, the analysis supports this model as an important tool for development of antifungal agents.

Bioequivalence and food effect assessment for vildagliptin/metformin fixed-dose combination tablets relative to free combination of vildagliptin and metformin in Japanese healthy subjects.

OBJECTIVE: To assess the bioequivalence of vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of vildagliptin and metformin following administration of 50/500 mg FDC tablets. METHODS: Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 - 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for vildagliptin and metformin. RESULTS: In both studies, vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. CONCLUSIONS: Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or vildagliptin.

Can community-based integrated vector control hasten the process of LF elimination?

Community-based integrated vector control (IVC) using polystyrene beads (EPS) and pyrethroid impregnated curtains (PIC) as an adjunct to mass drug administration (MDA) was implemented for lymphatic filariasis elimination, in the filaria endemic villages of Tirukoilur, south India. In all the villages, MDA was carried out by the state health machinery, as part of the national filariasis elimination programme. Thirty-six difficult-to-control villages were grouped as, viz, MDA alone, MDA + EPS and MDA + EPS + PIC arms. Implementation and monitoring of IVC was carried out by the community. After 3 years of IVC, higher reductions in filariometric indices were observed in both the community and vector population. Decline in antigenaemia prevalence was higher in MDA + IVC as compared to MDA alone arm. Vector density dropped significantly (P < 0.05) in both the IVC arms, and nil transmission was observed during post-IVC period. Almost 53.8 and 75.8 % of the cesspits in MDA + EPS and MDA + EPS + PIC arms were closed by the householders, due to the enhanced awareness on vector breeding. The paper presents the key elements of IVC implementation through social mobilization in a LF prevalent area. Thus, community-based IVC strategy can hasten LF elimination, as it reduced the transmission and filariometric indices significantly. Indices were maintained at low level with nil transmission, by the community through IVC tools.

The introduction of generic aromatase inhibitors and treatment adherence among Medicare D enrollees.

BACKGROUND: Aromatase inhibitors (AIs) substantially reduce breast cancer mortality in clinical trials, but high rates of nonadherence to these long-term oral therapies have reduced their impact outside of trials. We examined the association of generic AI availability with AI adherence among a large national breast cancer cohort. METHODS: Using a quasi-experimental prepost design, we examined the effect of generic AI introductions (7/2010 and 4/2011) on adherence among a national cohort of women with incident breast cancer in 2006 and 2007 who were enrolled in the Medicare D pharmaceutical coverage program. Medicare D claims were used to calculate AI adherence, defined as a medication possession ratio of 80% or more of eligible days, over 36 months. Multivariable logistic regression models estimated with generalized estimating equations were applied to longitudinal adherence data to control for possible confounders, including receipt of a Medicare D low-income subsidy, and to account for repeated measures. All statistical tests were two-sided. RESULTS: Sixteen thousand four hundred sixty-two Medicare D enrollees were eligible. Adherence declined throughout the study. However, among women without a subsidy, the median quarterly out-of-pocket cost of anastrozole fell from $183 in the fourth quarter of 2009 to $15 in 2011, and declines in adherence were attenuated with generic AI introductions. Regression-adjusted adherence probabilities were estimated to be 5.4% higher after generic anastrozole was introduced in 2010 and 11% higher after generic letrozole/exemestane was introduced in 2011. Subsidy recipients had higher adherence rates throughout the study. CONCLUSIONS: The introduction of generic medications attenuated the decline in adherence to AIs over three years of treatment among breast cancer survivors not receiving low-income subsidies for Medicare D coverage.

Box-Behnken study design for optimization of bicalutamide-loaded nanostructured lipid carrier: stability assessment.

Bicalutamide (BCM) is an anti-androgen drug used to treat prostate cancer. In this study, nanostructured lipid carriers (NLCs) were chosen as a carrier for delivery of BCM using Box-Behnken (BB) design for optimizing various quality attributes such as particle size and entrapment efficiency which is very critical for efficient drug delivery and high therapeutic efficacy. Stability of formulated NLCs was assessed with respect to storage stability, pH stability, hemolysis, protein stability, serum protein stability and accelerated stability. Hot high-pressure homogenizer was utilized for formulation of BCM-loaded NLCs. In BB response surface methodology, total lipid, % liquid lipid and % soya lecithin was selected as independent variable and particle size and %EE as dependent variables. Scanning electron microscopy (SEM) was done for morphological study of NLCs. Differential scanning calorimeter and X-ray diffraction study were used to study crystalline and amorphous behavior. Analysis of design space showed that process was robust with the particle size less than 200 nm and EE up to 78%. Results of stability studies showed stability of carrier in various storage conditions and in different pH condition. From all the above study, it can be concluded that NLCs may be suitable carrier for the delivery of BCM with respect to stability and quality attributes.