The PYRIN Domain-only Protein POP1 Inhibits Inflammasome Assembly and Ameliorates Inflammatory Disease.

In response to infections and tissue damage, ASC-containing inflammasome protein complexes are assembled that promote caspase-1 activation, IL-1ß and IL-18 processing and release, pyroptosis, and the release of ASC particles. However, excessive or persistent activation of the inflammasome causes inflammatory diseases. Therefore, a well-balanced inflammasome response is crucial for the maintenance of homeostasis. We show that the PYD-only protein POP1 inhibited ASC-dependent inflammasome assembly by preventing inflammasome nucleation, and consequently interfered with caspase-1 activation, IL-1ß and IL-18 release, pyroptosis, and the release of ASC particles. There is no mouse ortholog for POP1, but transgenic expression of human POP1 in monocytes, macrophages, and dendritic cells protected mice from systemic inflammation triggered by molecular PAMPs, inflammasome component NLRP3 mutation, and ASC danger particles. POP1 expression was regulated by TLR and IL-1R signaling, and we propose that POP1 provides a regulatory feedback loop that shuts down excessive inflammatory responses and thereby prevents systemic inflammation.

Recent insights into HSV infection and disease: results of wider genome analysis.

PURPOSE OF REVIEW: Technology to rapidly determine the partial or full genomic sequences of large viruses has developed rapidly in the last few years. Required sample sizes have diminished and sequencing of directly collected patient samples is now possible. Using banked samples from a number of clinical studies researchers have investigated how genomic variation may determine pathogenicity and answering important questions around the limits of vaccine therapy. RECENT FINDINGS: The natural variation in HSV-1 and HSV-2 geographically has been determined. Variation in the genes responsible for surface glycoproteins may explain the current limitations of therapy. Studies looking at genomic sequences for HSV-2 in subjects with recurrent disease and in those who took part in failed vaccine studies show that multiple HSV-2 strain infection is rare outside Africa and in those with immunodeficiency, whereas there is no evidence that vaccination drives viral evolution. Genome wide association studies have investigated rates of HSV shedding have failed to identify the link between subject genomic sequence and the severity. SUMMARY: These studies will help develop better diagnostics and vaccines that are likely to be more widely effective. The findings will help counsel patients. The factors determining HSV disease severity in individuals remain elusive.

Use of 2015 Beers Criteria Medications by Older Medicare Beneficiaries.

OBJECTIVE: To examine the prevalence of potentially inappropriate medications (PIMs) in community-dwelling Medicare beneficiaries based on the updated 2015 American Geriatrics Society Beers criteria. DESIGN: Cross-sectional study. SETTING: Thirteen mobile Medicare clinics were held throughout Northern and Central California during the fall of 2015. PATIENTS, PARTICIPANTS: Noninstitutionalized Medicare beneficiaries 65 years of age and older taking one or more medications. INTERVENTIONS: Pharmacy students under direct supervision of licensed pharmacists performed medication therapy management (MTM). Drug and disease state data were collected and used to identify PIMs based on the 2015 Beers criteria. MAIN OUTCOME MEASURES: Number of beneficiaries who are taking a PIM, have a potential drug-drug or drug-disease interaction, and common factors associated with receiving a PIM. RESULTS: MTM services were provided to 703 beneficiaries 65 years of age or older taking 1 or more medications. In total, 204 (29%) beneficiaries were taking 1 or more PIM. Drug-drug interactions were found in 54 beneficiaries, and 12 beneficiaries were found to have a significant drug-disease interaction. PIM prescribing was associated with certain chronic conditions (e.g., pain and insomnia). The prevalence of PIM use was significantly higher in women compared with men, whites compared with non-whites, and low-income beneficiaries compared with high income. CONCLUSION: Prescribers and pharmacists should work in concert to minimize PIM use in older adults. Practitioners knowledgeable about the updated 2015 Beers criteria may monitor drug use more closely, hopefully minimizing potentially harmful drug and/or disease-state problems, and preventing avoidable health-related sequelae.

Inequalities in access to genitourinary medicine clinics in the UK: results from a mystery shopper survey.

STUDY DESIGN: This study investigated whether access to genitourinary medicine (GUM) clinics meets UK-recommended standards. METHODS: In January 2014 and 2015, postal questionnaires about appointment and service characteristics were sent to lead clinicians of UK GUM clinics. In February 2014 and 2015, researchers posing as symptomatic and asymptomatic 'patients' contacted clinics by telephone, requesting to be seen. Clinic and patient characteristics associated with the offer of an appointment within 48 hours were examined using unadjusted and UK country and patient gender adjusted multivariable logistic regression analyses. In March 2015, a convenience sample (one in four) of clinics was visited by researchers with the same clinical symptoms. Ability to achieve a same-day consultation and waiting time were assessed. RESULTS: In 2015, 90.8% of clinics offered symptomatic 'patients' an appointment within 48 hours when contacted by telephone, compared with 95.5% in 2014 (aOR=0.46 (0.26 to 0.83); p<0.01). The decline was greatest in women (96.0% to 90.1%; p<0.05), and clinics in England (96.2% to 90.7%; p<0.01). For asymptomatic patients, the proportion offered an appointment within 48 hours increased from 50.7% in 2014 to 74.5% in 2015 (aOR=3.06 (2.23 to 4.22); p<0.001), and in both men (58.2% to 90.8%; p<0.001) and women (49.0% to 59.6%; p<0.01). In adjusted analysis, asymptomatic women were significantly less likely to be offered an appointment than asymptomatic men (aOR=0.33 (0.23 to 0.45); p value<0.001). 95% of clinics were able to see symptomatic patients attending in person. CONCLUSIONS: Access to GUM services has worsened for those with symptoms suggestive of an acute STI and is significantly poorer for asymptomatic women. This evidence may support the reintroduction of process targets.

An overview and study of beneficiaries' knowledge, attitudes, and perceptions of the medicare part d benefit.

PURPOSE: Medicare beneficiaries' knowledge, attitudes, and perceptions (KAP) of the Medicare Part D prescription drug benefit have been under evaluation since the 2006 inception of the Part D benefit. OBJECTIVE: This study sought to examine beneficiaries' satisfaction with their Medicare Part D prescription drug plan, knowledge of the coverage gap, attitudes about the relative importance of certain insurance parameters, and overall perceptions of the Part D benefit. DESIGN: Cross-sectional, descriptive study design. SETTING: Thirteen outreach events targeting Medicare beneficiaries in northern California during the 2012 open-enrollment period. PARTICIPANTS: A total of 576 Medicare beneficiaries. INTERVENTIONS: Beneficiaries were asked questions related to their KAP of the Part D benefit as part of a plan to evaluate their need for assistance. Sociodemographic data were collected via a standardized survey. MAIN OUTCOME MEASURES: Identify variances in KAP related to beneficiary sociodemographic and clinical characteristics. RESULTS: Forty-seven percent of beneficiaries claimed to be "very" or "extremely" satisfied with Part D, yet only 40.3% of those with a prescription drug plan (PDP) rated their plan as "very good" or "excellent." Those automatically enrolled into their plan by Medicare were significantly less satisfied with their plan (P = 0.048). Almost three in four recipients not receiving Medicare subsidies have heard of the gap in prescription drug coverage, i.e., the "donut hole." Additionally, there were significant racial disparities in knowledge of the gap. Only 62.7% of beneficiaries indicated that "total out-of-pocket cost during the year" was the most important plan characteristic for them. CONCLUSIONS: An understanding of beneficiaries' attitudes may help explain suboptimal Part D plan selection. Moreover, evaluating beneficiaries' knowledge of the Part D benefit can assist advocacy groups in creating educational materials to better assist this vulnerable population in choosing an appropriate plan.

Minimizing out-of-pocket prescription drug costs for Medicare beneficiaries: not just 'a drop in the bucket'.

OBJECTIVE: To identify the frequency of uptake and financial impact of four cost-minimization strategies used to assist Medicare beneficiaries in lowering their out-of-pocket (OOP) costs. DESIGN: Cost-savings analysis. SETTING: Twelve outreach events were conducted in six different cities throughout Northern and Central California during the 2013 Medicare open enrollment period. PARTICIPANTS: Noninstitutionalized Medicare beneficiaries from various socioeconomic backgrounds, including those receiving Medicaid. MAIN OUTCOME MEASURES: Potential OOP cost savings for the upcoming year. RESULTS: In total, 621 beneficiaries were assisted. Part D plan optimization was performed for 535 beneficiaries; the findings indicated that 435 (81%) could save money (average: $1,334) by switching plans in the upcoming year. The results also demonstrated that 28 beneficiaries could save money (mean: $1,274) through a patient assistance program. In total, 16 beneficiaries had self-reported income and/or assets that were low enough to qualify for additional governmental assistance through the low-income subsidy. Finally, less costly therapeutic alternatives were identified for 7 beneficiaries and prescribers accepted recommendations for change in 6 (85%) such cases. In total, beneficiaries could realize more than $770,000 in potential OOP savings from the performed interventions. CONCLUSION: Targeted assistance to beneficiaries through a variety of cost-lowering strategies can help significantly reduce OOP costs and thus may also result in lower cost-related medication nonadherence and improved beneficiary outcomes.

Impact of the COVID-19 Pandemic on US Pharmacy Academia Per Perspectives of Faculty and Administrators.

OBJECTIVE: The COVID-19 pandemic has markedly affected academic and administrative facets of pharmacy education. However, to date, no study has systematically summarized pandemic-related changes at pharmacy schools across the United States. This study aimed to evaluate US pharmacy school faculty and administrators' perspectives on the pandemic's impact on pharmacy academia. METHODS: A web-based survey was sent to US pharmacy school faculty and administrators in August 2020. The survey included questions assessing the pandemic's impact on the faculty's teaching, the school's financial status, administrative aspects, and mental well-being of faculty and administrators. Descriptive statistics and 1-sample Z tests were used for conducting statistical analyses. RESULTS: The survey was sent to 6177 individuals, of whom 1068 participated (17.3% response rate). In total, 931 respondents (759 faculty and 172 administrators) completed the entire survey. Both faculty and administrators experienced increased workload while their mental health and job satisfaction declined. Faculty's teaching satisfaction, research productivity, and service activity worsened. Administrators identified decreases in revenue sources and increases in expenses associated with the pandemic. Administrators also indicated the negative impact of the pandemic on an array of administrative and academic aspects within their pharmacy schools. The qualitative analysis identified several overlapping themes highlighting the negative effects of the pandemic on the faculty's teaching. CONCLUSION: Present findings indicate the negative effects of the COVID-19 pandemic on a variety of academic and administrative aspects at US pharmacy schools. These findings could provide useful information to stakeholders in pharmacy academia.

Prevalence and risk factors for inter-generational sex: a cross-sectional cluster survey of Barbadian females aged 15-19.

BACKGROUND: The aim of this study was to establish the prevalence and risk factors for intergenerational (IG)-sex in females aged 15-19 residing in Barbados. METHODS: This cross sectional cluster survey was conducted in a 2.6% national sample in the age range (n = 261) recruited from multiple polling districts chosen with a probability proportional to size. Consent was obtained from participants aged ≥18 years or from parents/guardians of participants <18 years, with participant assent. The prevalence of age at first sex was analyzed using a life table approach and risk factors for IG sex (defined as sexual relations with a male 10 or more years older) were analyzed by logistic regression, adjusting for age. RESULTS: 51.0% of adolescent females in the survey reported ever having had sex, among whom prevalence of IG-sex was 13.2% (95% CI: 6.7-19.8) at first sex, 29.0% (22.3-35.7) within the preceding twelve months, and 34.8% (24.3-45.4) ever. Condom use at first sex was positively related to willingness to have sex (F statistic = 9.8, p = 0.001). The strongest determinant for IG-sex was age of sexual debut (age adjusted Odds Ratio [95% CI]: 0.58[0.41-0.83]), followed by money or gifts received from the partner (2.91[1.17-7.23] and self-esteem (0.33[0.11-0.95]). CONCLUSIONS: The survey establishes a high rate of IG-sex in Barbados, a 'high income' country. Most insightful is that risk of IG-sex nearly halved for every year at which first sex was delayed. A high proportion of coerced sex was reported at first sexual experience and this was linked to poor condom use. Affirmative prevention approaches are recommended to boost self-acclamation of adolescent women within less coercive relationships, especially during their first sexual encounter.

The effects of pigs' feet consumption on lactation.

Pigs' feet are traditionally consumed by Korean women to increase milk production during lactation. In this study, we evaluated the perceived effectiveness and safety of consuming pigs' feet. Parous women were recruited to complete survey questionnaires in South Korea. Of the 516 respondents, 188 (36%) claimed they consumed pigs' feet. One-hundred twenty women (64%) who consumed pigs' feet reported experiencing an increase in breast milk production. Seventy-three (61%) women from this same group exclusively breastfed. In contrast, 16 (25%) of 65 respondents who did not embrace the same purported effect of pigs' feet indicated that they solely breastfed. Ninety-eight (82%) respondents who consumed pigs' feet and reported galactagoguic effects would recommend its use. Study findings reveal that the majority of women who consume pigs' feet believe in its milk-promoting effects. The results of this study suggest that further investigation of the galactagoguic effects of pigs' feet via conduction of an experimental study is warranted.

Respiratory Syncytial Virus Disease Burden in Community-Dwelling and Long-Term Care Facility Older Adults in Europe and the United States: A Prospective Study.

Background: Data on respiratory syncytial virus (RSV) disease burden in adults remain scarce. We assessed the burden of confirmed RSV-acute respiratory infections (cRSV-ARIs) in community-dwelling (CD) adults and those in long-term care facilities (LTCFs). Methods: In this prospective cohort study covering 2 RSV seasons (October 2019-March 2020 and October 2020-June 2021), RSV-ARIs were identified through active surveillance, in medically stable CD-adults ≥50 years (Europe) or adults ≥65 years in LTCFs (Europe and the United States). RSV infection was confirmed by polymerase chain reaction from combined nasal and throat swabs. Results: Of 1981 adults enrolled, 1251 adults in CD and 664 LTCFs (season 1) and 1223 adults in CD and 494 LTCFs (season 2) were included in the analyses. During season 1, overall incidence rates ([IRs] cases/1000 person-years) and attack rates (ARs) for cRSV-ARIs were 37.25 (95% confidence interval [CI], 22.62-61.35) and 1.84% in adults in CD and 47.85 (CI, 22.58-101.4) and 2.26% in adults in LTCFs. Complications occurred for 17.4% (CD) and 13.3% (LTCFs) of cRSV-ARIs. One cRSV-ARI occurred in season 2 (IR = 2.91 [CI, 0.40-20.97]; AR = 0.20%), without complications. No cRSV-ARIs led to hospitalization or death. Viral pathogens were codetected in ≤17.4% of cRSV-ARIs. Conclusions: RSV is an important cause of disease burden in adults in CD and LTCFs. Despite the observed low severity of cRSV-ARI, our results support the need for RSV prevention strategies among adults ≥50 years old.

Young persons' access to genitourinary medicine clinics in the UK: a cross-sectional survey.

STUDY DESIGN: This service evaluation of genitourinary medicine (GUM) clinics in the UK was designed to quantify access for young people requesting to be seen and to establish whether they could be seen outside school hours. METHODS: In December 2009 postal questionnaires were sent to all lead clinicians in UK GUM clinics asking when they expected a young person would be offered an appointment and whether it could be outside school hours. Between January and March 2010 trained male and female medical students posing as 16 year olds telephoned all GUM clinics listed on the British Association for Sexual Health and HIV website with symptomatic and asymptomatic scenarios and requested an appointment after school hours. RESULTS: 99% of the 152 responding clinicians estimated that an appointment would be offered within 48 h for both male and female contacts and over 90% could be seen outside school hours whether symptomatic or not. Of the 666 clinic telephone contacts, 88% were offered an appointment within two working days, and 66% were offered an after school appointment within 2 days. There was no significant difference whether the 'patient' was symptomatic or not (87% vs 86%, respectively, p=0.784) in being offered an appointment within two working days. There was variation between countries, with England performing significantly better; 94% were offered an appointment within 2 days versus 58%, 55% and 67% for Wales, Scotland and Northern Ireland, respectively. CONCLUSION: The findings would support the impact and value of process targets on service delivery.

Assessing quality of life in an ambulatory medicare population.

OBJECTIVE: Medicare beneficiaries have unique health-related challenges causing significant impact on quality of life. This study examined the overall health-related quality of life (HRQOL) and differences in HRQOL between subgroups of an ambulatory Medicare beneficiary population. METHODS: Nine outreach events were held during the 2011 Medicare Part D prescription drug open-enrollment period, in which 397 beneficiaries were assisted with Part D plan evaluation and comprehensive medication therapy review. Demographic data were collected, and the SF-36v2 was administered to measure beneficiaries' self-reported HRQOL. Correlations were assessed between the mental component summary (MCS) or physical component summary (PCS) scores of the SF-36v2, prescription utilization, number of chronic conditions, and whether beneficiaries were government subsidy recipients. RESULTS: Mean Å standard deviation of PCS and MCS scores were 43.3 Å 11.4 and 52.2 Å 11.7, respectively. Both PCS and MCS scores were negatively correlated with the number of prescription medications and number of self-reported chronic conditions. Both PCS and MCS scores related to sociodemographics were significantly lower (P < 0.05) in subsidy and least-educated recipients. CONCLUSIONS: HRQOL can vary widely as a result of sociodemographic, drug, or disease differences in an ambulatory Medicare beneficiary population.

Promoting access and reducing expected out-of-pocket prescription drug costs for vulnerable Medicare beneficiaries: a pharmacist-directed model.

BACKGROUND: The Medicare Part D benefit is complicated and may be costly, especially for vulnerable low-income populations where lack of resources and limited English proficiency may be barriers to optimal plan selection. OBJECTIVES: To identify vulnerable Medicare beneficiaries and lower their expected annual out-of-pocket (OOP) prescription drug costs through one-on-one prescription drug plan counseling by pharmacists and trained pharmacy students. RESEARCH DESIGN: Between October 2008 and January 2010, a cross-sectional study was performed throughout California. Using Medicare's Prescription Drug Plan Finder tool, expected annual OOP costs for each beneficiary's current prescription drug plan were compared with the lowest-cost plan. SUBJECTS: The study sample included vulnerable Medicare beneficiaries with annual incomes ≤300% of the Federal Poverty Level. RESULTS: There were 1300 vulnerable beneficiaries who received counseling at 94 outreach events. Only 29% of beneficiaries with a stand-alone Part D prescription drug plan were enrolled in the lowest-cost plan. On the basis of counseling recommendations, 390 beneficiaries changed to the lowest-cost Part D plan on site, reducing their expected OOP costs by 68%. Additionally, 72 beneficiaries were identified as eligible for but not receiving low-income subsidy benefits and 55 received assistance with the online application for the subsidy. CONCLUSIONS: Findings show that targeted outreach by trained pharmacy advocates can identify vulnerable Medicare populations in need of Part D counseling and reduce their expected annual OOP prescription drug costs.

Evaluation of patients' preferences for genital herpes treatment.

BACKGROUND: Genital herpes (GH) is widespread, and detrimental to patients' quality of life. It is not always adequately treated, however, with potential consequences for patients' well-being and healthcare costs. Involving patients in treatment decisions can increase their satisfaction and adherence. We investigated patients' preferences for different GH treatments. METHODS: A discrete choice experiment was administered to 154 subjects with GH. Subjects chose between different treatment options: episodic, suppressive, or no treatment, described according to: chance of GH recurrence; chance of transmitting the GH virus to a partner; chance of becoming infected with HIV; number of tablets to be taken every day and during an outbreak; and out-of-pocket cost. Subjects' willingness to pay and probability of treatment uptake were estimated. RESULTS: Subjects preferred antiviral treatment to no treatment, and subjects receiving suppressive treatment preferred this treatment to no treatment. Effect of treatment on GH recurrence and HIV infection rates was a significant influence on subject's choice, as were the number of tablets taken daily and during an outbreak and out-of pocket treatment cost. Subjects were willing to pay between $15.50 and $73.41 for treatment. Subjects' willingness to pay depends on the type of treatment and their current treatment. CONCLUSIONS: Subjects' preferences are influenced by both the treatment they follow and attributes of treatment including cost. Knowledge of patients' preferences, together with their clinical status, could help decision-makers to optimize therapy uptake and success.

Conference report: 34th IUSTI Europe Congress.

The 34th IUSTI European Conference was held from the 3rd to the 5th of October 2020. There were presentations on STIs in Europe, many centred on Romania. A full session was devoted to syphilis, including global efforts in syphilis vaccine development. A workshop on Pre-Exposure Prophylaxis (PrEP) implementation in Europe reviewed the 'PrEP gap' and the East/West divide with an additional presentation on upcoming PrEP technologies. The conference featured symposia from WHO: STIs are still increasing and with no Euro universal surveillance systems. Other symposia focused on health inequalities amongst gender and sexual minorities and the recently published changes in IUSTI guidelines on gonorrhoea, syphilis and Lymphogranuloma Venereum. SARS-CoV-2 was a focus for several plenary sessions and its possibly lasting impact on service delivery. New challenges were discussed, particularly the loss of azithromycin as a useful antimicrobial. The symposia covered latest research and work into genomics of STIs. Whole-genome sequencing has revolutionised infectious disease study, particularly infection transmission and control. There was a debate on whether 'screening and treatment of bacterial Sexually Transmitted Infection is associated with Antimicrobial Resistance and should be reconsidered', emphasising limited damage of asymptomatic infection and the possibility of emergence of rapid antibiotic resistance. The conference closed with several IUSTI awards.