Impact of scaling up dolutegravir on antiretroviral resistance in South Africa: A modeling study.

BACKGROUND: Rising resistance of HIV-1 to non-nucleoside reverse transcriptase inhibitors (NNRTIs) threatens the success of the global scale-up of antiretroviral therapy (ART). The switch to WHO-recommended dolutegravir (DTG)-based regimens could reduce this threat due to DTG's high genetic barrier to resistance. We used mathematical modeling to predict the impact of the scale-up of DTG-based ART on NNRTI pretreatment drug resistance (PDR) in South Africa, 2020 to 2040. METHODS AND FINDINGS: We adapted the Modeling Antiretroviral drug Resistance In South Africa (MARISA) model, an epidemiological model of the transmission of NNRTI resistance in South Africa. We modeled the introduction of DTG in 2020 under 2 scenarios: DTG as first-line regimen for ART initiators, or DTG for all patients, including patients on suppressive NNRTI-based ART. Given the safety concerns related to DTG during pregnancy, we assessed the impact of prescribing DTG to all men and in addition to (1) women beyond reproductive age; (2) women beyond reproductive age or using contraception; and (3) all women. The model projections show that, compared to the continuation of NNRTI-based ART, introducing DTG would lead to a reduction in NNRTI PDR in all scenarios if ART initiators are started on a DTG-based regimen, and those on NNRTI-based regimens are rapidly switched to DTG. NNRTI PDR would continue to increase if DTG-based ART was restricted to men. When given to all men and women, DTG-based ART could reduce the level of NNRTI PDR from 52.4% (without DTG) to 10.4% (with universal DTG) in 2040. If only men and women beyond reproductive age or on contraception are started on or switched to DTG-based ART, NNRTI PDR would reach 25.9% in 2040. Limitations include substantial uncertainty due to the long-term predictions and the current scarcity of knowledge about DTG efficacy in South Africa. CONCLUSIONS: Our model shows the potential benefit of scaling up DTG-based regimens for halting the rise of NNRTI resistance. Starting or switching all men and women to DTG would lead to a sustained decline in resistance levels, whereas using DTG-based ART in all men, or in men and women beyond childbearing age, would only slow down the increase in levels of NNRTI PDR.

Increasing access to care for chronic myeloid leukemia patients: assessment of a scaling-up program.

BACKGROUND: The Glivec International Patient Assistance Program (GIPAP) is designed to provide access to the cancer therapy Imatinib (Glivec⊠), which is indicated for the treatment of chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST). OBJECTIVES: To identify factors those influence the quality of care and structural improvements. Design . Physicians (n=50), hospital administrators (n=10) and Ministry of Health officials (n=7) in 39 developing countries participated in qualitative interviews. The interviews focused on the impact of GIPAP on service delivery, patient tracking systems and cancer registries, health financing, and workforce. RESULTS: Service delivery, patient management, access to care, diagnostic capacity, and health workers' skills improved at participants' institutions following implementation of GIPAP. CONCLUSIONS: Positive institutional changes that improve care of CML/GIST patients arose from GIPAP. Some of these changes may strengthen institutions' capacity to treat other diseases as well. The GIPAP model could be deployed to improve access to care for patients with other chronic diseases.

Improving access to care in low and middle-income countries: institutional factors related to enrollment and patient outcome in a cancer drug access program.

BACKGROUND: Limited access to drugs is a crucial barrier to reducing the growing impact of cancer in low- and middle-income countries. Approaches based on drug donations or adaptive pricing strategies yield promising but varying results across countries or programs, The Glivec International Patient Assistance Program (GIPAP) is a program designed to provide imatinib free of charge to patients with chronic myeloid leukemia (CML) or gastrointestinal stromal tumors (GIST). The objective of this work was to identify institutional factors associated with enrollment and patient survival in GIPAP. METHODS: We analyzed follow-up data from 4,946 patients participating in 47 institutions within 44 countries between 2003 and 2010. Active status in the program was considered as a proxy for survival. RESULTS: Presence of ≥1 hematologist or oncologist at the institution was associated with increased patient enrollment. After adjusting for individual factors such as age (>55 years: Hazard Ratio [HR] = 1.42 [1.16; 1.73]; p = 0.001) and initial stage of disease (accelerated or blast crisis at diagnosis: HR = 4.16 [1.87; 9.25]; p < 10⁻4), increased survival was found in institutions with research capabilities (HR = 0.55 [0.35; 0.86]; p = 0.01) and those with enrollment of >5 patients/year into GIPAP (HR = 0.48 [0.35; 0.67]; p < 10⁻4), while a non-significant trend for decreased survival was found for treatment at a public institution (HR = 1.32 [0.95; 1.84]; p = 0.10). The negative impact of an accelerated form of CML was attenuated by the presence of ≥1 hematologist or oncologist at the institution (interaction term HR = 0.43 [0.18; 0.99]; p = 0.05). CONCLUSIONS: Application of these findings to the support and selection of institutions participating in GIPAP may help to optimize care and outcomes for CML and GIST patients in the developing world. These results may also be applicable to the treatment of patients with other forms of cancer, due to the overlap of infrastructure and staff resources used to treat a variety of cancer indications. A multi-sector approach is required to address these barriers.

Treating chronic myeloid leukemia: improving management through understanding of the patient experience.

The tremendous progress made in chronic myeloid leukemia (CML) treatment affords patients more options than ever. Five currently available BCR-ABL inhibitors form the mainstay of CML treatment, including first-generation imatinib and more potent second-generation BCR-ABL inhibitors dasatinib and nilotinib, with bosutinib and ponatinib having been recently approved for market inclusion. Studies show that dasatinib and nilotinib exhibit greater efficacy than imatinib in first-line chronic-phase CML (CML-CP), allowing more patients to achieve deeper, more rapid responses associated with improved outcomes. With alternatives to imatinib for first-line CML-CP and the wealth of information (and misinformation) on the Internet, a tremendous need exists for clear, accurate facts to assist patients in making treatment decisions. Patients appreciate the guidance of their oncology nurse in providing disease, treatment, and monitoring information tailored to meet their needs. Oncology nurses who are able to clearly explain emerging data, including the meaning and significance of faster, deeper responses, will be a valuable resource to their patients.

The Global Online Sexuality Survey (GOSS): the United States of America in 2011 chapter II: phosphodiesterase inhibitors utilization among English speakers.

INTRODUCTION: Utility of phosphodiesterase inhibitors (PDEi's) for the treatment of erectile dysfunction (ED) has been the focus of experimental and clinical studies. However, public preferences, attitudes, and experiences with PDEi's are rarely addressed from a population/epidemiology viewpoint. The Global Online Sexuality Survey (GOSS) is a worldwide epidemiologic study of sexuality and sexual disorders, first launched in the Middle East in 2010, followed by the United States in 2011. AIM: To describe the utilization rates, trends, and attitudes toward PDEi's in the United States in the year 2011. METHODS: GOSS was randomly deployed to English-speaking male Web surfers in the United States via paid advertising on Facebook®, comprising 146 questions. MAIN OUTCOME MEASURES: Utilization rates and preferences for PDEi's by brand. RESULTS: Six hundred three subjects participated; mean age 53.43 years ± 13.9. Twenty-three point seven percent used PDEi's on more consistent basis, 37.5% of those with ED vs. 15.6% of those without ED (recreational users). Unrealistic safety concerns including habituation were pronounced. Seventy-nine point six percent of utilization was on prescription basis. PDEi's were purchased through pharmacies (5.3% without prescription) and in 16.5% over the Internet (68% without prescription). Nine point six percent nonprescription users suffered coronary heart disease. Prescription use was inclined toward sildenafil, generally, and particularly in severe cases, and shifted toward tadalafil in moderate ED and for recreational use, followed by vardenafil. Nonprescription utilization trends were similar, except in recreational use where sildenafil came first. CONCLUSION: In the United States unrealistic safety concerns over PDEi's utility exist and should be addressed. Preference for particular PDEi's over the others is primarily dictated by health-care providers, despite lack of guidelines that govern physician choice. Online and over-the-counter sales of PDEi's are common, and can expose a subset of users to health risks. Recreational use of PDEi's is common, and could be driven by undiagnosed premature ejaculation.

Classification, location and legitimacy of web-based suppliers of Viagra to the UK.

OBJECTIVES: to categorise online suppliers of Viagra based on their legal status, and to quantify the suppliers within each category. METHODS: Google was used to search for websites offering to sell or supply either proprietary Viagra tablets or generic versions containing sildenafil citrate. Relevant websites were classified as falling into one of three categories, which were further subclassified. Simple descriptive statistics were calculated. KEY FINDINGS: the number of relevant sites found within the first 100 Google hits, following the removal of mirror and affiliate sites, was 44. Only 6.8% of sites identified were legitimate online pharmacies. Some 34.1% of sites offered to sell Viagra to patients in the UK without any form of medical consultation. Whether or not the online consultation offered by 59.1% of sites had to be completed in order to make a purchase could not be confirmed. The location of only three pharmacies could be ascertained; the remainder made various claims as to their location, which could not be verified. CONCLUSIONS: we have been unable to verify that the questionnaires used for online consultations are scrutinised by any healthcare practitioners to determine the appropriateness of the treatment sought. This represents a serious safety concern for UK residents who procure drugs for erectile dysfunction on the internet.

From prescription-only to over-the-counter medicines ('PoM to P'): time for an intermediate category.

BACKGROUND: Increasing numbers of medicines are being made available over the counter in the UK, by purchase in a pharmacy or from other less well-regulated outlets. When this is allowed by the Licensing Authority, it is often subject to certain restrictions. However, some drugs that could usefully be converted from prescription-only medicines (PoM status) to over-the-counter sales in a pharmacy (P status) are not suitable for full over-the-counter status, even with restrictions; and in some cases restrictions vitiate the usefulness of the medicine. AREAS OF AGREEMENT: Drugs that can acceptably be switched from PoM status to P status include those that are used in the treatment of minor ailments or injuries, for health promotion or in palliative care. AREAS OF CONTROVERSY: However, not all drugs that are being switched fall into these categories. Ready availability of antimicrobial drugs over the counter, one of which (azithromycin) has recently been switched, could encourage the emergence of resistant organisms. Drugs that are used for long-term treatment and lifestyle drugs are also controversial, particularly if their adverse effects are of potential concern. On the other hand, the availability of many drugs via the internet removes the ability of regulators to control the supply of such drugs. A POSSIBLE SOLUTION: A new category of purchase, Pharmacist Consultation and Supply, with built-in safeguards, could improve the availability of some medicines under more careful control than is currently available for over-the-counter medicines.

Should sildenafil be available over the counter?

INTRODUCTION: This article considers the process of re-classification of prescription drugs from prescription-only medications to over-the-counter (OTC) prescription drugs. SOURCES OF DATA: The recent change in classification for emergency contraception and simvastatin is explored in detail with similarities and differences being considered for a similar argument to be made for sildenafil. AREAS OF AGREEMENT: The benefits for patients, physicians and other healthcare professionals are considered in detail. AREAS OF CONTROVERSY: We raise concerns about recently developed and existing patient group directions that, although extensive in their assessment, may omit to identify significant contributory factors which would necessitate appropriate medical intervention. GROWING POINTS: While the decision for re-classification to OTC would depend on a number of factors, we argue that, with the proviso of proper assessments being made, sildenafil should be made available as an OTC medication. AREAS TIMELY FOR DEVELOPING RESEARCH: The safety and use of OTC medications for erectile dysfunction at a time when many first line prescription agents are reaching generic status.

The GLIVEC international patient assistance programme: the Nairobi experience.

Glivec is a drug used in the treatment of chronic myeloid leukaemia (CML) and gastrointestinal stromal tumours (GISI). It is an expensive drug which would be out of reach for most patients in Kenya. Norvatis Pharmaceutical together with Axios International a healthcare management company and Max Foundation have made it possible for patients in developing countries to get access to the drug at no cost. Patients meet the cost of the confirmatory test and are recruited into the programme to receive the drug at no cost. A total of 201 patients are in the programme in Nairobi, mainly drawn from Kenyatta National Hospital the major referral hospital in Kenya. The age range is nine years to 75 years with a mean age of 39.5 years. Males make up 56.5% while females are 43.5%. CML are 173 (86%) while GIST patients are 28 (13.9%). Most of the CML cases are referred in the chronic stable phase (87.8%) and 85.7% have been on hydroxyurea as the initial treatment. Compliance rates are approximately 80%.

Confronting trade-offs in health care: Harvard Pilgrim Health Care's organizational ethics program.

Patients, providers, and policy leaders need a new moral compass to guide them in the turbulent U.S. health care system. Task forces have proposed excellent ethical codes, but these have been seen as too abstract to provide guidance at the front lines. Harvard Pilgrim Health Care's ten-year experience with an organizational ethics program suggests ways in which health care organizations can strengthen transparency, consumer focus, and overall ethical performance and contribute to the national health policy dialogue.

Viagra's rise above women's health issues: an analysis of the social and political influences on drug approvals in the United States and Japan.

In the United States, Viagra was approved in less than 6 months of its application to the Food and Drug Administration, while the medical abortion pill was approved 4 years after its application, and 17 years after research was first permitted. Congruently, the Ministry of Health in Japan legalized Viagra in 6 months, while oral contraceptives were approved 35 years after the ministry received initial applications. The pharmaceutical review agencies in each country are founded on safety and efficacy standards, in which objective decisions arise from science and clinical investigations. Analyses of these recent drug approvals demonstrate that conclusions may not have been based simply on science and health concerns. Instead, agency actions and application of pharmaceutical law appear to have been influenced by social and political pressures surrounding the products under scrutiny. Pharmaceutical regulations were effectively ignored or manipulated in the United States during the review process for medical abortion, and were applied inconsistently in Japan--ultimately yielding results that happened to conform to contemporary sociopolitical beliefs. Such disregard of legislation holds serious ramifications for public health, national consumer trust and the pharmaceutical industry. It is imperative that external pressures remain outside the scope of drug approval processes.

What to learn about sildenafil in the treatment of erectile dysfunction from 3-year clinical experience.

We retrospectively assessed the clinical uses and results of sildenafil in the treatment of erectile dysfunction (ED) in daily clinical practice from a cohort of 1658 subjects at a multispecialty medical center from 1999 to 2001 through a chart review, mailed questionnaire and telephone interview. The overall follow-up rate was 77.8% (1290/1658). The mean age was 63.8 y and ED duration was 3.4 y, and 44.6% of them had one or more concomitant conditions. The mean score of the International Index of Erectile Function erectile function domain was 12.7 in 314 nonselective subjects, and 75% of them had moderate to severe ED. The average number of purchase-visits and tablets of sildenafil purchased was 2.27 and 10.8 per person, respectively, and the prescription refill rate was 58.6%. Urology accounts for 91.4% of the specialties of prescribers. The response rate was 72.0%, which was significantly lower in subjects with diabetes, ischemic heart disease and following radical pelvic surgery than those without. Subjects with psychogenic etiology had the highest response rate, while those following radical pelvic surgery the lowest. Of the nonresponders, 67% did not try the maximum dose of 100 mg and 71.1% bought no more than four tablets. Adverse events were reported in 20.1% of the subjects. No one discontinued the treatment because of the adverse events. Mortality occurred in 17 subjects and none was considered related to sildenafil use. In conclusion, sildenafil was effective and safe in the treatment of ED in clinical practice. Compared with clinical trials or prospective clinical practice based studies, lack of dose titration, less follow-up visits and inadequate attempts before giving up were the main shortfalls in daily practice.