Relationship dynamics and anticipated stigma: Key considerations for PrEP use among Tanzanian adolescent girls and young women and male partners.

OBJECTIVES: We examined key gender, interpersonal and community dynamics influencing PrEP acceptability among adolescent girls and young women (AGYW) and their male partners. METHODS: We administered 12 in-depth interviews (IDI) to partnered, or married AGYW aged 15-24 years living without HIV, and 16 IDIs to male partners living without HIV aged 18 or older, partnered or married to an AGYW in Tanzania. Card sorting, a participatory qualitative method for facilitating systematic discussion, was used to identify attitudes, values, and desires that would influence PrEP acceptability. RESULTS: Relationship distrust, partner communication about HIV risk, and need to control HIV risk were highly influential considerations for PrEP use. AGYW and male partners both wanted to discuss PrEP use amidst relationship distrust, while most male partners encouraged AGYW PrEP use for shared protective benefit. Anticipated stigma of being perceived as a person living with HIV, as a result of PrEP use, was a deterrent for both AGYW and male partners while AGYW also feared additional stigma of being considered sexually promiscuous. CONCLUSIONS: Couples counseling for PrEP uptake and adherence might be a well-placed strategy for couples who are living without HIV to educate one another about the relationship benefits of using PrEP, thereby increasing its acceptance and adherence, addressing unequal power dynamics, and reducing associated relationship distrust. Community awareness and education about PrEP can help curb persistent PrEP stigma, including intersectional stigma.

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.

The past, present and future impact of HIV prevention and control on HPV and cervical disease in Tanzania: A modelling study.

BACKGROUND: Women with HIV have an elevated risk of HPV infection, and eventually, cervical cancer. Tanzania has a high burden of both HIV and cervical cancer, with an HIV prevalence of 5.5% in women in 2018, and a cervical cancer incidence rate among the highest globally, at 59.1 per 100,000 per year, and an estimated 9,772 cervical cancers diagnosed in 2018. We aimed to quantify the impact that interventions intended to control HIV have had and will have on cervical cancer in Tanzania over a period from 1995 to 2070. METHODS: A deterministic transmission-dynamic compartment model of HIV and HPV infection and natural history was used to simulate the impact of voluntary medical male circumcision (VMMC), anti-retroviral therapy (ART), and targeted pre-exposure prophylaxis (PrEP) on cervical cancer incidence and mortality from 1995-2070. FINDINGS: We estimate that VMMC has prevented 2,843 cervical cancer cases and 1,039 cervical cancer deaths from 1995-2020; by 2070 we predict that VMMC will have lowered cervical cancer incidence and mortality rates by 28% (55.11 cases per 100,000 women in 2070 without VMMC, compared to 39.93 with VMMC only) and 26% (37.31 deaths per 100,000 women in 2070 without VMMC compared to 27.72 with VMMC), respectively. We predict that ART will temporarily increase cervical cancer diagnoses and deaths, due to the removal of HIV death as a competing risk, but will ultimately further lower cervical cancer incidence and mortality rates by 7% (to 37.31 cases per 100,000 women in 2070) and 5% (to 26.44 deaths per 100,000 women in 2070), respectively, relative to a scenario with VMMC but no ART. A combination of ART and targeted PrEP use is anticipated to lower cervical cancer incidence and mortality rates to 35.82 and 25.35 cases and deaths, respectively, per 100,000 women in 2070. CONCLUSIONS: HIV treatment and control measures in Tanzania will result in long-term reductions in cervical cancer incidence and mortality. Although, in the near term, the life-extending capability of ART will result in a temporary increase in cervical cancer rates, continued efforts towards HIV prevention will reduce cervical cancer incidence and mortality over the longer term. These findings are critical background to understanding the longer-term impact of achieving cervical cancer elimination targets in Tanzania.

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.

Uncertain Effectiveness of Prophylactic Anticonvulsive Medication in Predicting Cognitive Outcome of Neurosurgical Patients.

OBJECTIVES: To evaluate the influence of prophylactic anticonvulsive medication, above all levetiracetam monotherapy, in predicting the cognitive outcome of neurosurgical patients with post-traumatic brain injury, intracerebral hemorrhage, and encephalic tumors. METHODS: We examined data concerning 232 of 327 adult patients admitted to the Neurorehabilitation Department of the San Raffaele Hospital (Milan, Italy) after discharge from the Neurosurgery Department. Cognitive status was evaluated by means of the "Mini-Mental State" examination and the Functional Independence Measure at baseline and at the end of a rehabilitation care with an average duration of about four weeks. RESULTS: The vast majority of the patients were treated with levetiracetam. Our data showed a negative role of antiepileptic drugs on cognitive recovery in a cohort of neurosurgical patients. CONCLUSIONS: Knowing thoroughly the effects of antiepileptic drugs in rehabilitation outcome is of fundamental importance. This study represents the only large series analyzing these aspects in the rehabilitation of neurosurgical patients. Antiepileptic drugs should be managed to ensure patients the best possible cognitive outcome. Further evidence from good-quality trials is required to assess the clinical effectiveness of prophylactic anticonvulsive medication in predicting the cognitive outcome of neurosurgical patients who are treated with rehabilitation.

Setting the scene, setting the targets. The Joint United Nations Programme on HIV/AIDS prevention targets of 2016 and estimating global pre-exposure prophylaxis targets.

Commitment to ambitious and time-bound targets for HIV interventions has been part of the response from the beginning of the HIV epidemic. The Joint United Nations Programme on HIV/AIDS (UNAIDS) HIV primary prevention workA is built on five pillars that include offering pre-exposure prophylaxis (PrEP) to population groups at substantial risk of HIV infection. After a slow start, countries are now setting coverage targets for PrEP, but the weakness of epidemiological, demographic and behavioural data at subnational level in many countries where there is a high burden of new HIV infections, makes it difficult to define the locations and populations where to offer PrEP. This article reviews the history and challenges of PrEP target setting and suggests some possible ways of strengthening the process. Reviewing program data will identify gaps in reaching key and other priority populations for whom coverage targets were set and help to refine the offer of PrEP.

Increasing prevalence of self-reported HIV preexposure prophylaxis use in published surveys: a systematic review and meta-analysis.

: When combining results from all published surveys, about one in nine global study participants (10.7%) reported ever using preexposure prophylaxis (PrEP) by 2017, a significant increase since US FDA approval in 2012 [odds ratio (OR) = 1.6/year, P < 0.00001]. Moreover, nearly one in six US-based study participants (17.3%) and nearly one in four MSM who met the Centers for Disease Control and Prevention's PrEP indications (24.5%) reported ever using PrEP by 2016. The odds of reporting PrEP use are approximately doubling each year (OR = 1.8/year, P < 0.00001; OR = 2.0/year, P < 0.00001).

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.

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.

Current practice regarding seizure prophylaxis in aneurysmal subarachnoid hemorrhage across academic centers.

OBJECT: The objective of this study was to determine current practices regarding seizure prophylaxis in aneurysmal subarachnoid hemorrhage (aSAH). METHODS: An eight question survey was sent to 25 US centers with high volume aSAH cases (>100 annually). Respondents were asked about institutional practices regarding use, duration, and type of seizure prophylaxis. RESULTS: 13 (52%) respondents endorsed the utility of seizure prophylaxis while 10 (40%) did not, and two (8%) were unsure. Among respondents using prophylaxis, levetiracetam was the firstline medication for the majority (94%) while phenytoin was used as a primary agent at one (4%) center and as a secondary agent at four (16%) centers. Duration of levetiracetam prophylaxis ranged from 1 day to 6 weeks following SAH (mean 13.2; median 11). Only a single center employed EEG routinely in all aSAH patients but most supported EEG use when the neurologic examination was unreliable or inexplicably declining. 24 (96%) respondents agreed that a trial randomizing patients to levetiracetam or no antiseizure medication is warranted at this time, and all 25 (100%) believed that such a trial would be appropriate or ethically sound. CONCLUSIONS: The routine use of seizure prophylaxis following aSAH is controversial. Among a sampling of 25 major academic centers, most administer prophylaxis, while a significant proportion does not. The majority believes a trial randomizing patients to receive seizure prophylaxis is both timely and ethical.