Comparative efficacy and safety of pharmacological prophylaxis and intermittent pneumatic compression for prevention of venous thromboembolism in adult undergoing neurosurgery: a systematic review and network meta-analysis.

Whether intermittent pneumatic compression (IPC) is a more effective form of thromboprophylaxis than anticoagulants in individuals undergoing neurosurgery remains controversial. Relevant studies are sparse and inconsistent. Therefore, direct comparisons are difficult to perform and impractical. Hence, we summarized and compared the efficacy and safety of IPC and anticoagulants for the prevention of venous thromboembolism (VTE) in adults undergoing cranial or spinal procedures. Several electronic databases were searched for randomized controlled trials on the use of IPC and anticoagulants for thromboembolism prevention in neurosurgical patients, from inception to August 6, 2019. Studies reporting the selected endpoints were included in direct and Bayesian network meta-analyses to estimate the relative effects of the interventions. Overall, our analysis included 18 trials comprising 2474 patients. Both IPC (RR, 0.41; 95% CrI, 0.26-0.60) and chemical prophylaxis (RR, 0.48; 95% CrI, 0.28-0.68) were found to be more efficacious than the placebo in reducing the risk of deep vein thrombosis (DVT). In addition, our analysis also demonstrated that both IPC (RR, 0.10; 95% CrI, 0.01-0.60) and chemical prophylaxis (RR, 0.31; 95% CrI, 0.05-1.00) reduced the risk of pulmonary embolism (PE) significantly more than the placebo. Based on the available evidence of moderate-to-good quality, IPC is equivalent to anticoagulants for thromboprophylaxis in terms of efficacy. Evidence to support or negate the use of pharmacological prophylaxis in terms of safety is lacking. The results of ongoing and future large randomized clinical trials are needed.

Prophylactic nimodipine treatment improves hearing outcome after vestibular schwannoma surgery in men: a subgroup analysis of a randomized multicenter phase III trial.

A 2016 published randomized multicenter phase III trial of prophylactic nimodipine treatment in vestibular schwannoma surgery showed only a tendency for higher hearing preservation rates in the treatment group. Gender was not included in statistical analysis at that time. A retrospective analysis of the trial considering gender, preoperative hearing, and nimodipine treatment was performed. The treatment group received parenteral nimodipine from the day before surgery until the seventh postoperative day. The control group was not treated prophylactically. Cochlear nerve function was determined by pure-tone audiometry with speech discrimination preoperatively, during in-patient care, and 1 year after surgery and classified according to the Gardner-Robertson grading scale (GR). Logistic regression analysis showed a statistically significant effect for higher hearing preservation rates (pre- and postoperative GR 1-4) in 40 men comparing the treatment (n = 21) and the control (n = 19) groups (p = 0.028), but not in 54 women comparing 27 women in both groups (p = 0.077). The results were also statistically significant for preservation of postoperative hearing with pre- and postoperative GR 1-3 (p = 0.024). There were no differences in tumor sizes between the treatment and the control groups in men, whereas statistically significant larger tumors were observed in the female treatment group compared with the female control group. Prophylactic nimodipine is safe, and an effect for hearing preservation in 40 men with preoperative hearing ability of GR 1-4 was shown in this retrospective investigation. The imbalance in tumor size with larger tumors in females of the treatment group may falsely suggest a gender-related effect. Further investigations are recommended to clarify whether gender has impact on nimodipine's efficacy.

National Trends in Drug Payments for HIV Preexposure Prophylaxis in the United States, 2014 to 2018 : A Retrospective Cohort Study.

BACKGROUND: Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown. OBJECTIVE: To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database. DESIGN: Retrospective cohort study. SETTING: Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions. MEASUREMENTS: Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments. RESULTS: Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance. LIMITATION: The IQVIA database does not capture every prescription nationwide. CONCLUSION: Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.

Pre-exposure prophylaxis for preventing acquisition of HIV: A cross-sectional study of patients, prescribers, uptake, and spending in the United States, 2015-2016.

BACKGROUND: In 2015, there were approximately 40,000 new HIV diagnoses in the United States. Pre-exposure prophylaxis (PrEP) is an effective strategy that reduces the risk of HIV acquisition; however, uptake among those who can benefit from it has lagged. In this study, we 1) compared the characteristics of patients who were prescribed PrEP with individuals newly diagnosed with HIV infection, 2) identified the specialties of practitioners prescribing PrEP, 3) identified metropolitan statistical areas (MSAs) within the US where there is relatively low uptake of PrEP, and 4) reported median amounts paid by patients and third-party payors for PrEP. METHODS AND FINDINGS: We analyzed prescription drug claims for individuals prescribed PrEP in the Integrated Dataverse (IDV) from Symphony Health for the period of September 2015 to August 2016 to describe PrEP patients, prescribers, relative uptake, and payment methods in the US. Data were available for 75,839 individuals prescribed PrEP, and findings were extrapolated to approximately 101,000 individuals, which is less than 10% of the 1.1 million adults for whom PrEP was indicated. Compared to individuals with newly diagnosed HIV infection, PrEP patients were more likely to be non-Hispanic white (45% versus 26.2%), older (25% versus 19% at ages 35-44), male (94% versus 81%), and not reside in the South (30% versus 52% reside in the South).Using a ratio of the number of PrEP patients within an MSA to the number of newly diagnosed individuals with HIV infection, we found MSAs with relatively low uptake of PrEP were concentrated in the South. Of the approximately 24,000 providers who prescribed PrEP, two-thirds reported primary care as their specialty. Compared to the types of payment methods that people living with diagnosed HIV (PLWH) used to pay for their antiretroviral treatment in 2015 to 2016 reported in the Centers for Disease Control and Prevention (CDC) HIV Surveillance Special Report, PrEP patients were more likely to have used commercial health insurance (80% versus 35%) and less likely to have used public healthcare coverage or a publicly sponsored assistance program to pay for PrEP (12% versus 45% for Medicaid). Third-party payors covered 95% of the costs of PrEP. Overall, we estimated the median annual per patient out-of-pocket spending on PrEP was approximately US$72. Limitations of this study include missing information on prescription claims of patients not included in the database, and for those included, some patients were missing information on patient diagnosis, race/ethnicity, educational attainment, and income (34%-36%). CONCLUSIONS: Our findings indicate that in 2015-2016, many individuals in the US who could benefit from being on PrEP were not receiving this HIV prevention medication, and those prescribed PrEP had a significantly different distribution of characteristics from the broader population that is at risk for acquiring HIV. PrEP patients were more likely to pay for PrEP using commercial or private insurance, whereas PLWH were more likely to pay for their antiretroviral treatment using publicly sponsored programs. Addressing the affordability of PrEP and otherwise promoting its use among those with indications for PrEP represents an important opportunity to help end the HIV epidemic.

Facing increased sexually transmitted infection incidence in HIV preexposure prophylaxis cohorts: what are the underlying determinants and what can be done?

PURPOSE OF REVIEW: The combined incidence of chlamydia, gonorrhoea and syphilis in MSM PrEP (preexposure prophylaxis) cohorts now frequently exceeds 100 per 100 person years. The efficacy of antiretroviral PrEP in reducing HIV transmission has led to efforts to find similar biomedical ways reduce sexually transmitted infection (STI) incidence. We review the recent evidence for these and other strategies. RECENT FINDINGS: Doxycycline PrEP/postexposure prophylaxis has been shown to reduce the incidence of syphilis and chlamydia but not gonorrhoea. A meningococcal vaccine has been found to result in a lower incidence of gonorrhoea. Novel insights into the role of the pharynx in the transmission of gonorrhoea have led to clinical trials of oral antiseptics to reduce the spread of gonorrhoea. Intensified STI screening has been introduced in a number of clinics. Serious concerns have however been raised about the emergence of resistance to each of these strategies. This is particularly true for doxycycline PrEP which is not advocated by any guidelines we reviewed. SUMMARY: Randomized controlled trials are urgently required to ascertain the benefits and risks of interventions to reduce STIs in MSM PrEP cohorts.

Appropriateness of using granulocyte colony-stimulating factor (G-CSF) for primary prophylaxis of febrile neutropenia in solid tumors.

INTRODUCTION: Febrile neutropenia (FN) is one of the dose-limiting adverse effects of chemotherapy. Granulocyte-Colony Stimulating Factors (G-CSFs) minimize the incidence of FN and reduce the risk of neutropenia complications. This study was conducted to address the prescription pattern of G-CSF for primary prophylaxis of FN during the first cycle of chemotherapy in solid tumors. METHOD: This prospective observational study was done to investigate the G-CSF prescription pattern in patients receiving the first cycle of chemotherapy for solid tumors and compare it with the NCCN guideline recommendations. RESULT: Based on the guideline, prophylactic G-CSF administration was indicated in 26 of the 96 patients (27.1%) and all of them received G-CSF. On the other hand, 70 patients (72.9%) did not meet the guideline criteria for prophylaxis, but 60 (62.5%) of them received G-CSF. Seven doses of pegfilgrastim and 165 doses of filgrastim were used inappropriately in the study population, which was associated with an economic burden of about 224.7 million IRR (5350 USD). CONCLUSION: Taken together, inconsistencies with the guideline were observed in this prospective evaluation, suggesting that submitting rationalized policies to decrease G-CSF prescription, especially in patients with a lower or intermediate FN risk, yields substantial cost savings.

Pre-exposure Prophylaxis (PrEP) Awareness and Use Within High HIV Transmission Networks.

Improved implementation of pre-exposure prophylaxis (PrEP) should be a valuable tool within communities experiencing high HIV incidence, such as black men who have sex with men (MSM). Using baseline data from the Chicago arm of the Transmission Reduction Intervention Project (TRIP), we examined awareness and use of PrEP within HIV potential transmission networks. Transmission Reduction Intervention Project recruited participants ages 18-69 (N = 218) during 2014-2016 from networks originating from recently and chronically HIV-infected MSM and transgender persons. In total, 53.2% of participants had heard of PrEP, while 8 (6.5%) HIV-negative participants reported ever using PrEP. In multivariable regression, PrEP awareness was associated with identifying as gay, attending some college or higher, having an HIV test in the previous 6 months, and experiencing HIV-related social support. PrEP awareness was not associated with experiencing or observing HIV-related stigma. PrEP use was associated with participants knowing two or more other PrEP-users. These findings demonstrate moderate awareness, but low uptake of PrEP within HIV potential transmission networks in Chicago. Future research should explore how to increase PrEP use in these networks and investigate the social dynamics behind our finding that PrEP users are more likely to know other PrEP users.

Trends in Attitudes to and the Use of HIV Pre-exposure Prophylaxis by Australian Gay and Bisexual Men, 2011-2017: Implications for Further Implementation from a Diffusion of Innovations Perspective.

Using repeated, national, online, cross-sectional surveys of Australian gay and bisexual men (GBM), we analysed trends related to HIV pre-exposure prophylaxis (PrEP). Specifically, we analysed trends in PrEP use, willingness to use PrEP, and concern about using PrEP during 2011-2017. We assessed support for GBM using PrEP and willingness to have sex with men taking PrEP between 2015 and 2017. For time-based analyses, we used multivariate logistic regression, controlling for sampling variations over time. We constructed new scales assessing reduced concern about HIV among PrEP users and non-users in 2017, and used multivariate logistic regression to identify independent correlates of PrEP use (vs. non-use). The analyses included 4567 HIV-negative and untested participants (2011-2017). PrEP use increased from 0.5% in 2011 to 25.5% in 2017 (p < 0.001). Willingness to use PrEP increased from 27.9% in 2011 to 36.5% in 2017 (p < 0.001) while concern about using PrEP fell (52.1-36.1%, p < 0.001). Support for GBM using PrEP remained stable (52.5% in 2015, 51.9% in 2017, p = 0.62), and willingness to have sex with men taking PrEP increased from 34.9% in 2015 to 49.0% in 2017 (p < 0.001). In 2017, 22.8% of non-PrEP-users had reduced HIV concern because of PrEP, while 73.6% of PrEP users had reduced HIV concern and greater sexual pleasure because of PrEP. The analysis of PrEP users vs. non-users in 2017 indicated that PrEP users were more sexually active and reported higher risk sexual practices, were more likely to live in New South Wales and Victoria, and to be in full-time employment. They were also more likely to know HIV-positive people and other PrEP users. Diffusion of Innovations theory suggests that future PrEP users in Australia may be less adventurous and require greater reassurance about PrEP's efficacy and legitimacy, to sustain rollout and address current disparities in uptake.

Predictors of PrEP Uptake Among Patients with Equivalent Access.

Increasing PrEP adoption for eligible individuals is critical, but limited research has examined individual-level factors that might be amenable to educational or behavioral intervention. Using data from a PrEP demonstration project conducted at a community health center, we examined differences in behavioral and psychosocial factors between patients offered PrEP who chose to accept it and those who declined. In a multivariable model, the odds of accepting PrEP were higher among those with an HIV-positive main partner, greater risk behavior in the past 3 months, and higher HIV risk perception. PrEP adoption was positively associated with PrEP adherence self-efficacy and negatively associated with perceived sensitivity to medicines. These psychological variables were associated with measures of PrEP- and HIV-related stigma. In the multivariable model, there were no differences in PrEP adoption by demographic factors or socioeconomic status. Data suggest that patients' decisions about PrEP uptake may be impacted not only by objective and subjective HIV risk, but also by psychological variables such as stigma beliefs, medication beliefs, and self-efficacy.

Antiemetic Prophylaxis as a Marker of Health Care Disparities in the National Anesthesia Clinical Outcomes Registry.

BACKGROUND: US health care disparities persist despite repeated countermeasures. Research identified race, ethnicity, gender, and socioeconomic status as factors, mediated through individual provider and/or systemic biases; little research exists in anesthesiology. We investigated antiemetic prophylaxis as a surrogate marker for anesthesia quality by individual providers because antiemetics are universally available, indicated contingent on patient characteristics (gender, age, etc), but independent of comorbidities and not yet impacted by regulatory or financial constraints. We hypothesized that socioeconomic indicators (measured as insurance status or median income in the patients' home zip code area) are associated with the utilization of antiemetic prophylaxis (as a marker of anesthesia quality). METHODS: We tested our hypothesis in several subsets of electronic anesthesia records from the National Anesthesia Clinical Outcomes Registry (NACOR), fitting frequentist and novel Bayesian multilevel logistic regression models. RESULTS: NACOR contained 12 million cases in 2013. Six institutions reported on antiemetic prophylaxis for 441,645 anesthesia cases. Only 173,133 cases included details on insurance information. Even fewer (n = 92,683) contained complete data on procedure codes and provider identifiers. Bivariate analysis, multivariable logistic regression, and our Bayesian hierarchical model all showed a large and statistically significant association between socioeconomic markers and antiemetic prophylaxis (ondansetron and dexamethasone). For Medicaid versus commercially insured patients, the odds ratio of receiving the antiemetic ondansetron is 0.85 in our Bayesian hierarchical mixed regression model, with a 95% Bayesian credible interval of 0.81-0.89 with similar inferences in classical (frequentist) regression models. CONCLUSIONS: Our analyses of NACOR anesthesia records raise concerns that patients with lower socioeconomic status may receive inferior anesthesia care provided by individual anesthesiologists, as indicated by less antiemetics administered. Effects persisted after we controlled for important patient characteristics and for procedure and provider influences. Findings were robust to sensitivity analyses. Our results challenge the notion that anesthesia providers do not contribute to health care disparities.

'It's just an excuse to slut around': gay and bisexual mens' constructions of HIV pre-exposure prophylaxis (PrEP) as a social problem.

Since the 2012 FDA approval of HIV Pre-exposure Prophylaxis (PrEP) as a method to prevent HIV, its uptake among gay and bisexual men has been met with conflict. Drawing on discussions of PrEP from focus groups with gay and bisexual men in New York City (N = 5 groups, n = 32 participants), we sought to make meaning of the moral debate surrounding the implementation of biomedical HIV prevention medications. Grounded in the constructionist perspective on social problems, this case study focuses on the competing claims making activities gay and bisexual men engage in when framing PrEP and PrEP users. As HIV prevention is a communicative endeavour, analysing the micro level social problems work on PrEP provides key insight into the subcultural norms and values that shape sexual health practices and beliefs within gay and bisexual communities.

Diffuse large B-cell lymphoma with testicular involvement: outcome and risk of CNS relapse in the rituximab era.

The addition of rituximab has improved outcomes in diffuse large B-cell lymphoma (DLBCL), however, there remains limited information on the impact of rituximab in those with testicular involvement. All patients with diffuse large cell lymphoma and testicular involvement treated with curative intent were identified in the British Columbia Cancer Agency Lymphoid Cancer Database. In total, 134 patients diagnosed between 1982 and 2015 with diffuse large cell lymphoma involving the testis were identified: 61 received CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone)-like chemotherapy and 73 received CHOP plus rituximab (R-CHOP). A greater proportion of R-CHOP treated patients had higher International Prognostic Index (IPI, P = 0·005). In multivariate analysis, the protective effect of rituximab on progression-free survival (hazard ratio (HR) 0·42, P < 0·001), overall survival (HR 0·39, P < 0·001) and cumulative incidence of progression (HR 0·46, P = 0·014) were independent of the IPI. However, in a competing risk multivariate analysis including central nervous system (CNS) prophylaxis and the CNS-IPI, rituximab was not associated with a decreased risk of CNS relapse. The addition of rituximab has reduced the risk of lymphoma recurrence in testicular DLBCL, presumably through improved eradication of systemic disease. However, CNS relapse risk remains high and further studies evaluating effective prophylactic strategies are needed.

Persistence and switching patterns of oral migraine prophylactic medications among patients with chronic migraine: A retrospective claims analysis.

Background Migraine prevention guidelines recommend oral prophylactic medications for patients with frequent headache. This study examined oral migraine preventive medication (OMPM) treatment patterns by evaluating medication persistence, switching, and re-initiation in patients with chronic migraine (CM). Methods A retrospective US claims analysis (Truven Health MarketScan® Databases) evaluated patients ≥18 years old diagnosed with CM who had initiated an OMPM between 1 January, 2008 and 30 September, 2012. Treatment persistence was measured at six and 12 months' follow-up. Time-to-discontinuation was assessed for each OMPM and compared using Cox regression models. Among those who discontinued, the proportion that switched OMPMs within 60 days or re-initiated treatment between 61 to 365 days, and their associated persistence rates, were also assessed. Results A total of 8707 patients met the inclusion/exclusion criteria. Persistence to the initial OMPM was 25% at six months and 14% at 12 months. Based on Kaplan-Meier curves, a sharp decline of patients discontinuing was observed by 30 days, and approximately half discontinued by 60 days. Similar trends in time-to-discontinuation were seen following the second or third OMPM. Amitriptyline, gabapentin, and nortriptyline had significantly higher likelihood of non-persistence compared with topiramate. Among patients who discontinued, 23% switched to another prophylactic and 41% re-initiated therapy within one year. Among patients who switched, persistence was between 10 to 13% and among re-initiated patients, persistence was between 4 to 8% at 12 months. Conclusions Persistence to OMPMs is poor at six months and declines further by 12 months. Switching between OMPMs is common, but results indicate that persistence worsens as patients cycle through various OMPMs.

Migraine Prophylaxis and Acute Treatment Patterns Among Commercially Insured Patients in the United States.

OBJECTIVES: To describe prophylactic and acute medication treatment patterns, including timing, medication type, and duration of use in migraine patients initiating prophylaxis. BACKGROUND: Patients with migraine can be treated with acute and prophylactic therapies. Current treatment options for migraine prophylaxis are associated with poor tolerability and low adherence and persistence. METHODS: This retrospective cohort study used the Truven Health Analytics MarketScan® Research Databases to identify adults in the United States with a migraine diagnosis who initiated migraine prophylactic medication (index event) between January 1, 2008, and December 31, 2011. Prescribed prophylactic medications evaluated included topiramate, beta-blockers, and tricyclic antidepressants. Patients were required to have 12 months of pre- and post-index continuous enrollment. Patient characteristics, migraine-specific prescribed prophylactic treatment patterns (including gaps in therapy, treatment switches, and additions of index medications), and prescribed acute medication utilization were assessed. RESULTS: The study population comprised 107,122 patients, with 52,275 (49%) initiating topiramate, 22,658 (21%) initiating beta-blockers, and 32,189 (30%) initiating tricyclic antidepressants. Mean (SD) age was 41 (12) years and 83% were female. Persistence with migraine prophylactic medication was low; 81% of patients had gaps of >90 days in their migraine prophylaxis in the first year. The gap in therapy occurred early in treatment (mean, 95 days), and only 10% of patients restarted prophylactic therapy within that year. Switching from index medication to another prophylactic medication or adding prophylaxis was uncommon (13% and 5%, respectively). One year after initiating prophylaxis, 65% of patients were not receiving any prophylactic therapies. Most patients initiating migraine prophylaxis also utilized acute treatments (81%); opioid use was more frequent than triptan use (53% vs 48%) and was common (40%) among patients without other chronic pain conditions (eg, arthritis, fibromyalgia, and lower back pain). CONCLUSION: Patients with migraine who initiated prophylactic therapy had poor persistence with early gaps in therapy, were unlikely to switch prophylactic treatments, and most discontinued prophylaxis by the end of the first year.

A Translational Pharmacology Approach to Predicting Outcomes of Preexposure Prophylaxis Against HIV in Men and Women Using Tenofovir Disoproxil Fumarate With or Without Emtricitabine.

BACKGROUND: A novel translational pharmacology investigation was conducted by combining an in vitro efficacy target with mucosal tissue pharmacokinetic (PK) data and mathematical modeling to determine the number of doses required for effective human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP). METHODS: A PK/pharmacodynamic (PD) model was developed by measuring mucosal tissue concentrations of tenofovir, emtricitabine, their active metabolites (tenofovir diphosphate [TFVdp] and emtricitabine triphosphate [FTCtp], respectively), and competing endogenous nucleotides (dATP and dCTP) in 47 healthy women. TZM-bl and CD4(+) T cells were used to identify 90% effective concentration (EC90) ratios of TFVdp to dATP and FTCtp to dCTP (alone and in combination) for protection against HIV. Monte-Carlo simulations were then performed to identify minimally effective dosing strategies to protect lower female genital tract and colorectal tissues. RESULTS: The colorectal TFVdp concentration was 10 times higher than that in the lower female genital tract, whereas concentrations of endogenous nucleotides were 7-11 times lower. Our model predicted that ≥98% of the population achieved protective mucosal tissue exposure by the third daily dose of tenofovir disoproxil fumarate plus emtricitabine. However, a minimum adherence to 6 of 7 doses/week (85%) was required to protect lower female genital tract tissue from HIV, while adherence to 2 of 7 doses/week (28%) was required to protect colorectal tissue. CONCLUSIONS: This model is predictive of recent PrEP trial results in which 2-3 doses/week was 75%-90% effective in men but ineffective in women. These data provide a novel approach for future PrEP investigations that can optimize clinical trial dosing strategies.

Defining Appropriate Use of Proton-Pump Inhibitors Among Medical Inpatients.

BACKGROUND: Proton-pump inhibitors (PPIs) are commonly used among medical inpatients, both for prophylaxis against upper gastrointestinal bleeding (UGIB) and continuation of outpatient use. While PPIs reduce the risk of UGIB, they also appear to increase the risk of hospital-acquired pneumonia (HAP) and Clostridium difficile infection (CDI). Depending upon the underlying risks of these conditions and the changes in those risks with PPIs, use of proton-pump inhibitors may lead to a net benefit or net harm among medical inpatients. OBJECTIVE: We aimed to determine the net impact of PPIs on hospital mortality among medical inpatients. DESIGN: A microsimulation model, using literature-derived estimates of the risks of UGIB, HAP, and CDI among medical inpatients, along with the changes in risk associated with PPI use for each of these outcomes. The primary outcome was change in inpatient mortality. PARTICIPANTS: Simulated general medical inpatients outside the intensive care unit (ICU). MAIN MEASURE: Change in overall mortality during hospitalization. KEY RESULTS: New initiation of PPI therapy led to an increase in hospital mortality in about 90% of simulated patients. Continuation of outpatient PPI therapy on admission led to net increase in hospital mortality in 79% of simulated patients. Results were robust to both one-way and multivariate sensitivity analyses, with net harm occurring in at least two-thirds of patients in all scenarios. CONCLUSIONS: For the majority of medical inpatients outside the ICU, use of PPIs likely leads to a net increase in hospital mortality. Even in patients at particularly high risk of UGIB, only those at the very lowest risk of HCAP and CDI should be considered for prophylactic PPI use. Continuation of outpatient PPIs may also increase expected hospital mortality. Apart from patients with active UGIB, use of PPIs in hospitalized patients should be discouraged.

Pharmaceutical HIV prevention technologies in the UK: six domains for social science research.

The development of pharmaceutical HIV prevention technologies (PPTs) over the last five years has generated intense interest from a range of stakeholders. There are concerns that these clinical and pharmaceutical interventions are proceeding with insufficient input of the social sciences. Hence key questions around implementation and evaluation remain unexplored whilst biomedical HIV prevention remains insufficiently critiqued or theorised from sociological as well as other social science perspectives. This paper presents the results of an expert symposium held in the UK to explore and build consensus on the role of the social sciences in researching and evaluating PPTs in this context. The symposium brought together UK social scientists from a variety of backgrounds. A position paper was produced and distributed in advance of the symposium and revised in the light this consultation phase. These exchanges and the emerging structure of this paper formed the basis for symposium panel presentations and break-out sessions. Recordings of all sessions were used to further refine the document which was also redrafted in light of ongoing comments from symposium participants. Six domains of enquiry for the social sciences were identified and discussed: self, identity and personal narrative; intimacy, risk and sex; communities, resistance and activism; systems, structures and institutions; economic considerations and analyses; and evaluation and outcomes. These are discussed in depth alongside overarching consensus points for social science research in this area as it moves forward.

"In reality, it is complex and difficult": UK nurses' perspectives on "treatment as prevention" within HIV care.

Globally, clinical guidelines for HIV treatment are being altered to reflect new research showing that successful treatment with antiretroviral therapies (ART) can prevent the onward transmission of HIV. As a result, health care services are being challenged to find ways to roll out "treatment as prevention" (TasP) as a public health measure. In theory, TasP requires individuals to start ART as soon as they are diagnosed - for public health reasons - which may be some time before ART for that individual is required for clinical reasons. There is currently little research on the acceptability of TasP from a patient or provider perspective. This paper reports findings from a qualitative study that sought to explore UK nurses' views and experiences of TasP in HIV care. Ten HIV specialist nurses, purposively selected from across the country, were interviewed. Results suggest that, although positive about TasP in principle, nurses hold several reservations about its implementation in practice. Perceived benefits of TasP include reassurance for patients that their loved ones are protected and that immediate care is available. Concerns include the possibility of sexual dis-inhibition or coercion within sexual relationships. In the UK context, decisions around TasP are still being made on a highly individualised patient by patient basis, within a philosophy of holistic care and partnership working. As such, the research participants called for more resources to support information giving, risk assessment and decision-making. The results show that translating a public health treatment approach into individual patient care is complex, potentially time-consuming and may alter traditional provider-patient dynamics. The findings from this study suggest that in-depth research is needed to understand better the patient, community and provider experience as TasP becomes more widely rolled out.

Predictors for uptake of intermittent preventive treatment of malaria in pregnancy (IPTp) in Tanzania.

BACKGROUND: Tanzania adopted Intermittent-preventive treatment of malaria in pregnancy (IPTp) policy in 2000; the guidelines at the time of the study recommended the timing of the first dose of intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) (IPTp-SP) at 20-24 weeks and the timing of the second dose at 28-32 weeks. The aim of this study was to identify factors that are responsible for the uptake of IPTp among pregnant Tanzanian women. Further, this study aims to justify the need for appropriate interventions that would strengthen the Tanzanian IPTp program towards the realization of the Roll Back Malaria (RBM) targets. METHODS: Data were analyzed from the 2011-2012 Tanzania HIV and Malaria Indicators Survey (THMIS) of 1,616 women aged 15-49 years who had a live birth in the 2 years prior to the survey and received antenatal care (ANC) services. RESULTS: Logistic regression analysis results showed that (1) being in the age groups 30-34 and 35-39 versus other age groups and being married or living with partner versus those who reported as never married or divorced/separated were associated with high uptake of IPTp; (2) women pregnant with their first or second child versus those who already have had two or more children had higher odds of completing the recommended number of IPTp dosage; and (3) being a resident from the Eastern Zone versus Lake Zone as well as having the first antenatal visit in the first or second trimester versus third trimester were associated with higher uptake of IPTp. CONCLUSION: Applying these results could contribute to positive social change by helping providers, clinics, and organizations seeking to increase IPTp uptake among ANC attendees and providing health education programs to women, especially those residing in rural areas. This study could also help achieve United Nations Millennium Development Goals (MDG) 6 (combat HIV/AIDS, Malaria and Other Diseases).