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Drug–drug interactions (DDIs) are one of the most frequent causes of adverse drug reactions or loss of treatment efficacy. The risk of DDIs increases with polypharmacy and is therefore of particular concern in individuals likely to present comorbidities (i.e., elderly or obese individuals). These special populations, and the population of pregnant women, are characterized by physiological changes that can impact drug pharmacokinetics and consequently the magnitude of DDIs. This review compiles existing DDI studies in elderly, obese, and pregnant populations that include a control group without the condition of interest. The impact of physiological changes on the magnitude of DDIs was then analyzed by comparing the exposure of a medication in presence and absence of an interacting drug for the special population relative to the control population. Aging does not alter the magnitude of DDIs as the related physiological changes impact the victim and perpetrator drugs to a similar extent, regardless of their elimination pathway. Conversely, the magnitude of DDIs can be changed in obese individuals or pregnant women, as these conditions impact drugs to different extents depending on their metabolic pathway.

Glycopyrronium bromide, a synthetic anticholinergic agent used to treat patients with chronic obstructive pulmonary disease (COPD), is eliminated from the body by renal excretion and therefore systemic exposure is expected to be increased in patients with decreasing renal function. Despite enrollment of patients with decreasing renal function to evaluate the impact of renal impairment on the pharmacokinetics of glycopyrronium in clinical studies, no patients with severe renal impairment were included. A physiologically based pharmacokinetic (PBPK) model was developed in patients with COPD with normal renal function and used to predict systemic exposure of glycopyrronium in patients with severe renal impairment. The model accurately predicted plasma concentration-time profiles in patients with normal renal function, and mild and moderate renal impairment; the predicted and observed AUC and C max in these populations were similar. Compared to patients with normal renal function, a 1.20-, 1.45-, and 1.59-fold increase AUC was predicted in patients with mild, moderate, and severe renal impairment, respectively, suggesting dose adjustment is not necessary in patients with renal impairment. In conclusion, PBPK models, verified with clinical study data from patients with normal renal function, can potentially be used to predict the pharmacokinetics and recommended dose adjustment for patients with renal impairment. [ABSTRACT FROM AUTHOR]

Background and Objective: Moisturizing products are widely used in conditions affecting skin hydration. However, the lack of scientific evidence leads to discrepancies and great variability in the recommendations used by different health professionals. The aim of this consensus document is to generate recommendations based on the evidence and experience of dermatologists to unify and facilitate the use of moisturizing products in the routine clinical practice., Materials and Methods: A 49-statement questionnaire on moisturizing products was prepared and, then, arranged in 5 blocks: 1) concept; 2) characteristics, 3) frequency and quantity, 4) product use and areas of application, and 5) special populations. Twenty-two expert dermatologists in the management of patients with eczema answered to the survey using a 2-round Delphi methodology (adding an item on the 2 nd round)., Results: Consensus was reached on 27 statements (54%), most (n=23) via agreement. The highest level of agreement was reached in the blocks on quantity, product use and areas of application (77.8%), followed by the blocks on characteristics (73%) and frequency (62.5%). Regarding the blocks on concept and special populations, the level of consensus on the items proposed was 37.5% and 10%, respectively. Consensus on the use of emollients for xeroderma (71%) was higher vs atopic dermatitis (64%) and inflamed skin (33.3%)., Conclusions: Consensus recommendations can help all prescribers and improve the available evidence regarding their use., (Copyright © 2024 AEDV. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Human papillomavirus (HPV) causes 99.7% of cervical cancer cases. Cervical cancer is preventable through early detection via HPV testing. However, the number of women screened for cervical cancer has not increased in the last several years. Lower screening rates among women living in high poverty and social vulnerability areas, Black women, and women with chronic co-morbidities (e.g., type 2 diabetes (T2D)) are associated with their higher cervical cancer mortality rates. When screened, Black women are more likely to be diagnosed at later stages and die from cervical cancer. HPV self-collection decreases barriers to cervical cancer screening and can help lessen disparities among underserved women. This study aimed to examine the acceptability of HPV self-collection among Black women with T2D living in socially vulnerable communities., Methods: Qualitative semi-structured interviews were conducted with 29 Black women with T2D living in communities with high social vulnerability. The Health Belief Model informed the development of the interview guide to gather data on the acceptability of HPV self-collection., Results: Three main themes aligned with the Health Belief Model were identified: (1) HPV self-collection provides a comfortable alternative to in-clinic HPV testing (perceived benefits); (2) HPV self-collection would result in awareness of current HPV status (health motivation); and (3) Women were concerned about collecting their sample accurately (perceived barriers)., Discussion/conclusion: Black women with T2D living in communities with high social vulnerability identified multiple benefits of cervical cancer screening through HPV self-collection. Women are concerned about their ability to collect these samples correctly. Our findings call for future studies focusing on increasing self-efficacy and skills to collect HPV samples among Black women with chronic conditions like T2D who reside in underserved communities with high social vulnerability., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

A treatment gap exists for pediatric patients with renal impairment. Alterations in renal clearance and metabolism of drugs render standard dosage regimens inappropriate and may lead to drug toxicity, but these studies are not routinely conducted during drug development. The objective of this study was to examine the clinical evidence behind current renal impairment dosage recommendations for pediatric patients in a standard pediatric dosing handbook. The sources of recommendations and comparisons included the pediatric dosing handbook (Lexicomp), the U.S. Food and Drug Administration‐approved manufacturer's labels, and published studies in the literature. One hundred twenty‐six drugs in Lexicomp had pediatric renal dosing recommendations. Only 14% (18 of 126) of Lexicomp pediatric renal dosing recommendations referenced a pediatric clinical study, and 15% of manufacturer's labels (19 of 126) described specific dosing regimens for renally impaired pediatric patients. Forty‐two products had published information on pediatric renal dosing, but 19 (45%) were case studies. When pediatric clinical studies were not referenced in Lexicomp, the renal dosing recommendations followed the adult and pediatric dosing recommendations on the manufacturer's label. Clinical evidence in pediatric patients does not exist for most renal dosing recommendations in a widely used pediatric dosing handbook, and the adult renal dosing recommendations from the manufacturer's label are currently the primary source of pediatric renal dosing information. [ABSTRACT FROM AUTHOR]

Objective: The objective of the study was to review the current literature for prophylactic enoxaparin dosing in obese orthopedic patients. Method: A literature search was undertaken using OVID Medline, OVID Embase, and Cochrane Central databases, accessed through hospital library websites. Key search terms (in UK and US spelling) included orthopaedics, low-molecular-weight heparin, enoxaparin, venous thromboembolism prophylaxis, weight, obese, morbid obesity. Possible related subheadings, such as bone, fractures, anticoagulants, overweight, body mass index, deep vein thrombosis, pulmonary embolism, were also included in the database search to optimize the search strategies. The search was restricted to human subjects and limited to articles published from 1998 to the present. Results: The search identified 429 potentially relevant articles. Once duplicates were removed, 345 were screened for inclusion in this review. Only 3 articles (a case-control study, an observational prospective study, and a case report) met both the inclusion and exclusion criteria. The findings from this review need to be interpreted cautiously due to limitations in study designs and the potential for confounding bias. Conclusion: The results of a multiple database search draw one to the conclusion that there is very limited evidence in the literature with regard to prophylactic enoxaparin dosing in obese orthopedic-specific patients. Orthopedic patients are among the highest risk of all surgical specialties for venous thromboembolism. There is strong evidence to support an increased prophylactic low-molecular-weight heparin doses in obese patients; thus, the authors recommend higher prophylactic enoxaparin dosing in obese orthopedic patients. [ABSTRACT FROM AUTHOR]

Disease states such as liver cirrhosis and chronic kidney disease can lead to altered pharmacokinetics (PK) of drugs by influencing drug absorption, blood flow to organs, plasma protein binding, apparent volume of distribution, and drug‐metabolizing enzyme and transporter (DMET) abundance. Narrow therapeutic index drugs are particularly vulnerable to undesired pharmacodynamics (PD) because of the changes in drug PK in disease states. However, systematic clinical evaluation of disease effect on drug PK and PD is not always possible because of the complexity or the cost of clinical studies. Physiologically based PK (PBPK) modeling is emerging as an alternate method to extrapolate drug PK from the healthy population to disease states. These models require information on the effect of disease condition on the activity or tissue abundance of DMET proteins. Although immunoquantification‐based abundance data were available in the literature for a limited number of DMET proteins, the emergence of mass spectrometry‐based quantitative proteomics as a sensitive, robust, and high‐throughput tool has allowed a rapid increase in data availability on tissue DMET abundance in healthy versus disease states, especially in liver tissue. Here, we summarize these data including the available immunoquantification or mRNA levels of DMET proteins (healthy vs disease states) in extrahepatic tissue and discuss the potential applications of DMET abundance data in enhancing the capability of PBPK modeling in predicting drug disposition across disease states. Successful examples of PBPK modeling that integrate differences in DMET proteins between healthy and disease states are discussed. [ABSTRACT FROM AUTHOR]

The human papillomavirus (HPV) potentially affects every sexually active man in the United States and Canada. In 2017, the vaccine became publicly funded in Canada for males ages 9–26, and was integrated into school vaccination programs. In 2019, HPV vaccination was recommended as routine for all U.S.-based males and females ages 9 through 26, and a shared decision for adults >26 years; however, since the approval of the vaccine in 2006 for females only, the age and dosing recommendations for males have followed a complicated and changing trajectory. Current adherence rates are low among college and university age males (18–26 years); therefore, understanding and addressing the barriers and facilitators for men's HPV vaccination is critically important. The purpose of the current scoping review is to provide a synthesis of recent literature pertaining to HPV in college and university age men, as a means to guiding health-care providers (HCPs). Drawing from 15 published articles, three thematic findings were inductively derived. Theme one, lack of awareness, was underpinned by men's knowledge deficits about their eligibility for, and the availability of HPV vaccines. Theme two, underestimating and embodying risk, included men's engagement in sexual activities while misinformed or denying the risk for contracting HPV. The third theme, strategies for increasing men's awareness, summarizes messaging strategies used to lobby young men to vaccinate. The review findings indicate gender-sensitive interventions targeting college-age men, including early, frequent, and consistent messaging on HPV are key. [ABSTRACT FROM AUTHOR]

When are interventions appropriate? Diana Sylvestre, a renegade doctor in Oakland, disputes current approaches to two major medical epidemics: the liver-destroying virus hepatitis C, and its outcast counterpart, addiction. At the Oasis clinic, this maverick doctor and her ragtag clientele - a small army of drug addicts - are (loudly) trying to change the rules of "intervention." This is the astonishing story of how they arrived at their strategy, which threads medical science with a deeply counterintuitive approach to addiction.

Despite the significant health disparities experienced by lesbian, gay, bisexual, and transgender (LGBT) populations, few investigators affiliated with the National Institutes of Health-funded Clinical and Translational Science Award Programs are conducting research related to this underserved population. We provide recommendations shared during a half-day workshop aimed at increasing researcher readiness to conduct LGBT research. This workshop was presented as part of a series on conducting research with underserved populations offered by the Recruitment, Retention, and Community Engagement Program of the Center for Clinical and Translational Science at the University of Illinois at Chicago. Six LGBT health research experts provided focused presentations. The workshop presentations included a summary of significant health inequality issues, theoretical models relevant to research on LGBT health, best practices in measuring sexual orientation and gender identity, recommendations for recruitment and retention, a discussion of community engagement, and ethical considerations in conducting LGBT research. We provide a summary of recommendations to guide future research, training, and public policy related to LGBT health. The information can increase capacity among Clinical and Translational Science Award affiliated researchers in conducting research in this special population.

Antibiotic efficacy determination in clinical trials often relies on non-inferiority designs because they afford smaller study sample sizes. These efficacy studies tend to exclude patients within specific populations or include too few patients to discern potential differences in their clinical outcomes. As a result, dosing guidance in patients with abnormal liver and kidney function, age across the lifespan, and other specific populations relies on drug exposure-matching. The underlying assumption for exposure-matching is that the disease course and the response to the antibiotic are similar in patients with and without the specific condition. While this may not be the case, clinical efficacy studies are underpowered to ensure this is true. The current paper provides an integrative review of the current approach to dose selection in specific populations. We review existing clinical trial endpoints that could be measured on a more continuous rather than a discrete scale to better inform exposure–response relationships. The inclusion of newer systemic biomarkers of efficacy can help overcome the current limitations. We use a modeling and simulation exercise to illustrate how an efficacy biomarker can inform dose selection better. Studies that inform response-matching rather than exposure-matching only are needed to improve dose selection in specific populations.

BACKGROUND: Few studies examine why rural public schools have weaker policies and practices related to school nutrition environments compared to their urban counterparts. It is important to understand this disparity because federal school meal standards aim for children to access health‐promoting nutrition environments. In this study, we identify challenges and opportunities for the implementation of school meal standards in rural high schools. METHODS: We interviewed 38 rural school professionals from 22 high schools across 7 states. School professionals included food service directors, principals, school nurses, and teachers. Team coding in Atlas.ti Qualitative Data Analysis software v8 and principles of comparative analysis were employed to generate themes related to challenges and opportunities. RESULTS: Overall, school professionals described improvements with implementation experiences and student acceptance over time. Key challenges included the negative influences of home and community food environments and limited staff size and capacity. Key opportunities involved joining co‐ops to enhance purchasing power, leveraging state technical assistance, and forming external partnerships. CONCLUSIONS: This study offers insights from a broad range of rural school professionals' implementation experiences. The findings can inform governments and technical assistance agencies working with rural schools and school districts to facilitate implementation and sustainability of initiatives. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed at understanding the perceptions of people with physical disabilities regarding playing Light Volleyball (LVB), identifying the possible constraints and risks they might face while playing, and providing their suggestions for fine-tuning the Light Volleyball intervention programmes. Method: Four focus group interviews were conducted with 17 participants who joined the Light Volleyball trial programme. The participants were 11 males and 6 females, with an average age of 53.5 years (SD=11.83 years). People with poliomyelitis (n = 15), spinal cord injury (n = 1), hearing impairment (n = 1) were included. Results: Participants indicated improved reactivity and coordination, cooperation in team, happiness, and novelty in general as positive outcomes while playing Light Volleyball. They preferred to play in the seated position (i.e., sitting light volleyball - SLVB), and with simpler rules. They believed that their ability to play Light Volleyball was subject to their body constraints. Conclusion: Sitting Light Volleyball can be one of the new physical activity options for future sport promotion among people with physical disabilities in the community. The effectiveness of playing Sitting Light Volleyball in enhancing health among people with physical disabilities needs to be studied in future. [ABSTRACT FROM AUTHOR]

Objectives: This study examined the associations between childhood household dysfunction and adulthood past-year DSM-5 alcohol, tobacco, and other substance use disorders across sexual orientation subgroups (eg, lesbian/gay, bisexual, and heterosexual). Methods: Prevalence estimates were based on National Epidemiologic Survey on Alcohol and Related Conditions (NESARC-III) data collected from structured diagnostic face-to-face interviews in a nationally representative sample of 36,309 U.S. adults. Multivariable regression was used to examine associations between childhood household dysfunction and past-year substance use disorders in adulthood. Results: Sexual minorities, particularly sexual minority women, reported higher rates of childhood household dysfunction (eg, parental/ household history of substance-related problems) and adulthood DSM-5 alcohol, tobacco, and substance use disorders. Results of multivariable analyses indicated that childhood histories of parental/ household substance-related problems were associated with greater odds of past-year substance use disorders among sexual minorities than heterosexuals, and that such histories may moderate differences among sexual orientation subgroups. The risk of substance use disorders among sexual minority women relative to exclusively heterosexual women (ie, heterosexual-identified women without same-sex attraction or behavior) remained high, even when accounting for household dysfunction. In contrast, there were no such differences between sexual minority men and exclusively heterosexual men. Conclusions: Sexual minorities are more likely to have childhood household dysfunction which in turn is associated with a higher risk of developing DSM-5 alcohol, tobacco, and substance use disorders in adulthood, especially among sexual minority women. Healthcare providers who care for individuals raised in dysfunctional households should carefully assess risk for substance use disorders and intervene as needed. [ABSTRACT FROM AUTHOR]

We have searched the literature for information on the risk of breast cancer (BC) in relation to gender, breast development, and gonadal function in the following 8 populations: 1) females with the Turner syndrome (45, XO); 2) females and males with congenital hypogonadotropic hypogonadism and the Kallmann syndrome; 3) pure gonadal dysgenesis (PGD) in genotypic and phenotypic females and genotypic males (Swyer syndrome); 4) males with the Klinefelter syndrome (47, XXY); 5) male-to-female transgender individuals; 6) female-to-male transgender individuals; 7) genotypic males, but phenotypic females with the complete androgen insensitivity syndrome, and 8) females with Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome (müllerian agenesis). Based on this search, we have drawn 3 major conclusions. First, the presence of a Y chromosome protects against the development of BC, even when female-size breasts and female-level estrogens are present. Second, without menstrual cycles, BC hardly occurs with an incidence comparable to males. There is a strong correlation between the lifetime number of menstrual cycles and the risk of BC. In our populations the BC risk in genetic females not exposed to progesterone (P4) is very low and comparable to males. Third, BC has been reported only once in genetic females with MRKH syndrome who have normal breasts and ovulating ovaries with normal levels of estrogens and P4. We hypothesize that the oncogenic glycoprotein WNT family member 4 is the link between the genetic cause of MRKH and the absence of BC women with MRKH syndrome. [ABSTRACT FROM AUTHOR]

The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for amoxicillin for non-pregnant, pregnant and postpartum populations by compiling a database incorporating reported changes in the anatomy and physiology throughout the postpartum period. A systematic literature search was conducted to collect data on anatomical and physiological changes in postpartum women. Empirical functions were generated describing the observed changes providing the basis for a generic PBPK framework. The fraction unbound ( f u ) of predominantly albumin-bound drugs was predicted in postpartum women and compared with experimentally observed values. Finally, a specific amoxicillin PBPK model was newly developed, verified for non-pregnant populations and translated into the third trimester of pregnancy (29.4–36.9 gestational weeks) and early postpartum period (drug administration 1.5–3.8 h after delivery). Pharmacokinetic predictions were evaluated using published clinical data. The literature search yielded 105 studies with 1092 anatomical and physiological data values on 3742 postpartum women which were used to generate various functions describing the observed trends. The f u could be adequately scaled to postpartum women. The pregnancy PBPK model predicted amoxicillin disposition adequately as did the postpartum PBPK model, although clearance was somewhat underestimated. While more research is needed to establish fully verified postpartum PBPK models, this study provides a repository of anatomical and physiological changes in postpartum women that can be applied to future modeling efforts. Ultimately, structural refinement of the developed postpartum PBPK model could be used to investigate drug transfer to the neonate via breast-feeding in silico. [ABSTRACT FROM AUTHOR]

In this report, we describe the implementation and short-term outcomes of a Special Populations Consultation Service within the University of California, Los Angeles (UCLA) Clinical and Translational Science Institute (CTSI). With the goal of increasing the quality and quantity of special population (SP) research, the UCLA CTSI Integrating Special Populations program designed a consultation service to support faculty and trainees conducting research involving one of three CTSI "special populations:" children, older adults, and/or minority; underserved; or health disparity populations. The Special Populations Consultation Service offers three types of activities: grant proposal studios, career consultations, and project reviews. UCLA CTSI faculty with appropriate content expertise serve as consultants. We evaluated this consultation model using satisfaction surveys and by quantifying funded grants and reported changes in career goals in SP research. Between 2016 and 2019, the Special Populations Consultation Service provided 59 consultations including 42 grant studios and was used by researchers at all levels from all four UCLA CTSI institutions. Recipients rated the consultations very highly. Funding success rates were 57% following K-level grant studios and 28% following R-level grant studios. Users of project and career consultations commonly attributed career accomplishments in part to their consultation experiences. The SP Consultation Service is feasible and acceptable and appears to enhance careers of investigators studying special populations. [ABSTRACT FROM AUTHOR]

Latinx men in the southern United States are affected disproportionately by HIV and other sexually transmitted infections (STIs). However, few evidence-based prevention interventions exist to promote health equity within this population. Developed by a well-established community-based participatory research partnership, the HoMBReS por un Cambio intervention decreases sexual risk among Spanish-speaking, predominately heterosexual Latinx men who are members of recreational soccer teams in the United States. Scale-up and spread, an implementation science framework, was used to study the implementation of this evidence-based community-level intervention within three community organizations that represent typical community-based providers of HIV and STI prevention interventions (i.e., an AIDS service organization, a Latinx-serving organization, and a county public health department). Archival and interview data were analyzed, and 24 themes emerged that mapped onto the 12 scale-up and spread constructs. Themes included the importance of strong and attentive leadership, problem-solving challenges early, an established relationship between innovation developers and implementers, organizational capacity able to effectively work with men, trust building, timelines and incremental deadlines, clear and simple guidance regarding all aspects of implementation, appreciating the context (e.g., immigration-related rhetoric, policies, and actions), recognizing men's competing priorities, and delineated supervision responsibilities. Scale-up and spread was a useful framework to understand multisite implementation of a sexual risk reduction intervention for Spanish-speaking, predominately heterosexual Latinx men. Further research is needed to identify how constructs, like those within scale-up and spread, affect the process across the implementation continuum, given that the uptake and implementation of an innovation is a process, not an event. [ABSTRACT FROM AUTHOR]

Few real‐life studies evaluated long‐term apremilast therapy in the variable spectrum of clinical‐anamnestic features which can be found in psoriatic arthritis (PsA) patients. This real‐life retrospective observational study aimed to assess long‐term efficacy, safety, and tolerability of apremilast among patients with PsA and concomitant cutaneous psoriasis. A stratified analysis was performed on special populations, defined as (a) number (≤1 vs >2) of comorbidities, presence or absence of: (b) history of malignancy, and (c) previous exposure to biologics. Patients attending three Italian University and Hospital centers, who received at least one dose of apremilast and had at least one follow‐up visit were included. Ninety‐six patients with PsA were identified. Psoriasis Area and Severity Index (PASI), Body Surface Area, 28‐joint Disease Activity Score, and Dermatology Life Quality Index scores improved during treatment, already at week 4, relative to baseline. More than 2 comorbidities, history of malignancy and previous biologic treatment negatively influenced PASI responses. At least one adverse event was experienced by 56/96 patients, and 11/56 events required drug withdrawal. In conclusion, this study confirm efficacy and safety of apremilast on joints and skin involvement of PsA, highlighting which patients could have less favorable treatment response. [ABSTRACT FROM AUTHOR]

BACKGROUND: Transgender, nonbinary, and gender nonconforming (TNG) young people are a diverse group, including young people with gender identities beyond the gender binary. Whereas nonbinary youth experience disparities in victimization and mental health, school belonging, support, and resources have not been well described. METHODS: We conducted an online survey of TNG young people (ages 12‐22) in Wisconsin to assess school belonging, safety, support, and resources. We compared responses among participants with nonbinary versus binary identities using mulvariate analysis of variance, multivariate analysis of covariance, chi‐square and logistic regression analysis. RESULTS: A total of 287 TNG young people met inclusion criteria (average age 18.2 ± 2.5 years). More than 40% of participants identified as nonbinary. Nonbinary participants were less likely to be out to teachers, but more likely to utilize supportive staff as a resource compared to binary‐identified TNG peers. There were no significant differences in school safety and belonging. CONCLUSIONS: Most school experiences do not vary significantly between TNG young people with binary versus nonbinary gender identities, though nonbinary young people are less likely to be out at school. Future research should examine factors that impact whether nonbinary young people share their gender identity and access school support services. [ABSTRACT FROM AUTHOR]

A decades-long decline in sperm counts in Western countries has coincided with an increase in obesity rates, prompting study into their association. Few of these studies have incorporated men of color, the sperm health of whom is relatively unknown. The present exploratory study evaluated the association between body mass index (BMI), race, ethnicity, and sperm parameters among a diverse sample of U.S. men attending a Washington, DC physician practice. Semen samples were collected and processed at a single laboratory and sperm concentration, motility, morphology, and count were evaluated according to World Health Organization (WHO) 5th edition criteria. Multivariate models accounted for covariates related to sperm health. The study population (n = 128) was largely obese (45.3%) or overweight (34.4%), and 36.0% were black or Hispanic. Black men had lower adjusted sperm concentration compared to white men (75.0 million/mL to 107.4 million/mL, p =.01) and were more likely to have oligozoospermia (p =.01), asthenozoospermia (p =.004), and low sperm count (p <.0001). Hispanic men had higher adjusted sperm concentration compared to non-Hispanic men (124.5 million/mL to 62.1 million/mL, p =.007) and were less likely to have teratozoospermia (p =.001). Obesity and BMI were associated with lower sperm motility and count in crude models only. Given the study's sample size its findings should be interpreted with caution but align with the limited epidemiological literature to date that has evaluated racial and ethnic differences in semen quality. Heightened clinical research attention is needed to ensure men of color are included in representative numbers in studies of urologic and andrologic health. [ABSTRACT FROM AUTHOR]

Exercise is important for optimal recovery and quality of life for lower limb amputees. General guidelines for training to improve quality of life, gait retraining, and attenuation of risk factors for lower limb amputees will be outlined. Exercise prescription outlined in this column for lower limb amputees is based on the amputee's progress and stage of rehabilitation. [ABSTRACT FROM AUTHOR]

"Special populations" refer to groups of people whose needs are not fully addressed by traditional health services delivery. Greater access to these services, or tailored services, must be provided to reduce inequities in physical and mental health-care systems. Many different groups have been identified as special populations. We comment on controversies regarding the use of the term special populations in health practice and policy. Applicable conceptual issues include intersectionality, unitization, definitional drawbacks, and looping effects. There is a need to make clear the challenges posed by use of this term (e.g., discrimination, workability). An approach that acknowledges the diversity of groups and accommodates them where necessary without discrimination and unequal treatment is needed. [ABSTRACT FROM AUTHOR]

The aim of this study was to assess outcomes from a multilevel social network intervention to promote the health of Black men. Through a community–academic collaboration and using a participatory research approach, we implemented the intervention over 4 years in a 110-block area of an urban neighborhood. The project aimed to implement a neighborhood peer outreach and leadership network to strengthen social support of Black men and increase community and family engagement. Intervention activities included three 12-month intergenerational peer support groups (N = 46), a door-to-door outreach campaign (N = 186), media and communication efforts, and a community partner network. Primary outcomes for the peer support groups were measured using a pretest/posttest cohort design and included social support, perceived stress, social capital, and global self-esteem. Primary outcomes for the door-to-door outreach campaign were measured using a repeated cross-sectional design and included a sense of community, neighborhood social interaction, perceived neighborhood control, and self-rated health status. Significant findings from the peer support groups included an increase in social support overall (p =.027), driven by improvements in guidance, reliable alliance, and reassurance of worth; and an improvement in perceived stress (p =.047). Significant findings from the door-to-door outreach campaign included increases in neighborhood social interaction (p <.0001) and perceived neighborhood control (p =.036). This project provides evidence that a participatory approach to planning and delivering a health promotion intervention aimed at creating positive social spaces and enhancing social connections can result in significant outcomes and successful engagement of Black men. [ABSTRACT FROM AUTHOR]

Neonatal infections are a major cause of newborn mortality in low- and middle-income countries, particularly in areas without access to inpatient care. To address this, the World Health Organization developed guidelines for delivering simplified antibiotic regimens (oral amoxicillin and intramuscular gentamicin) in outpatient settings to young infants with suspected serious bacterial infection when referral is not feasible. However, there are still limitations to access, as the regimen requires a health care provider trained in giving intramuscular injections to infants. To provide a needle-free, simplified alternate to intramuscular delivery, PATH investigated the feasibility of the rectal administration of gentamicin. Potential formulations were screened by in vitro testing, and 2 liquid enema formulations and a cocoa butter suppository were developed and evaluated in a preclinical study of the rectal uptake of gentamicin in a neonatal minipig model. Sera samples from the control group, dosed by intramuscular injection, resulted in expected sera concentrations of gentamicin, but no gentamicin was detected in the sera of groups rectally dosed with the test formulations. The results of this study did not provide evidence to support the therapeutic feasibility of rectally absorbed gentamicin. [ABSTRACT FROM AUTHOR]

Purpose: Previous studies that addressed whether left ventricular hypertrophy is more closely associated with central than peripheral blood pressure (BP) have been inconsistent. Radial artery wave generated by applanation tonometry and calibrated with brachial BP in 162 adult Nigerians were analysed by using generalized transfer function to derive central BP. Materials and methods: We compared the associations of ECG voltages and left ventricular hypertrophy (ECG-LVH) as continuous and binary variables respectively with central and brachial BP indices. Results: In a multivariable adjusted analysis, 1 standard deviation (SD) increase in brachial systolic, diastolic, pulse and mean arterial pressures increased the Sokolow–Lyon QRS voltage by 0.34 (CI, 0.21–0.48; p < 0.0001), 0.21 (CI, 0.07–0.36; p < 0.05); 0.22 (CI, 0.9–0.34; p < 0.001) and 0.29 (CI, 0.14–0.43) similar to (p > 0.05) corresponding Sokolow–Lyon QRS increase of 0.26 (0.12–0.40, p < 0.001); 0.14 (0.00–0.28, p < 0.05); 0.24 (0.11–0.39; p < 0.001) and 0.19 (0.05–0.34, p < 0.05) respectively observed for 1 SD increment in central pressures. The odds ratio (OR) relating ECG-LVH to 1 SD increase in brachial systolic, pulse, and mean arterial pressures were 2.62 (CI, 1.49–4.65, p < 0.001); 1.88 (CI, 1.19–2.95, p < 0.01) and 2.16 (CI, 1.22–3.82, p < 0.01) was similar to (p > 0.05) corresponding OR of 2.41 (1.33–4.36, p < 0.01); 2.04 (1.23–3.37, p < 0.01); 2.00 (1.11–3.63, p < 0.001) observed for I SD increment in central pressures. Conclusion: Central and peripheral BP are similarly associated with Sokolow–Lyon ECG voltage and hypertrophy. [ABSTRACT FROM AUTHOR]

While the past two decades have seen rapid advances in research demonstrating links between environmental health and reproductive capacity, African American men have largely been overlooked as study participants. To give voice to the perceptions of urban African American men, the present qualitative study conducted focus groups of men recruited from street- and internet-based advertisements in Washington, DC. Participants were asked for their perspectives on their environment, reproductive health and fertility, and factors that would influence their participation in public health research. Participants expressed concern about ubiquitous environmental exposures characteristic of their living environments, which they attributed in part to gentrification and urban development. Infertility was seen as a threat to masculinity and a taboo subject in the African American community and several participants shared personal stories describing a general code of silence about the subject. Each group offered multiple suggestions for recruiting African American men into research studies; facilitators for study participation included cultural relevance, incentives, transparent communication, internet- and community-based recruitment, and use of African Americans and/or recruiters of color as part of the research team. When asked whether participants would participate in a hypothetical study on fertility that involved providing a sperm sample, there was a mixed reaction, with some expressing concern about how such a sample would be used and others describing a few facilitators for participation in such a study. These are unique perspectives that are largely missing from current-day evidence on the inclusion of African American men in environmental health and reproductive health research. [ABSTRACT FROM AUTHOR]

Attachment studies with diverse populations enrich the understanding of infants' socioemotional development by documenting both universal and idiosyncratic aspects of attachment. Given the effects of attachment in children's socioemotional outcomes, such studies are necessary to investigate the impact of children's sensory impairments on attachment development. Yet, very little attachment research has focused on infants with visual impairment (VI infants), a population in which infant–caregiver emotional exchanges through visual means are reduced/absent. We investigated the applicability of the Strange Situation Paradigm (SSP), with added instructions to compensate for degraded visual input, in 20 VI infants (with no additional disabilities and who were receiving developmental counseling). In all but 1 of the SSPs coded, VI infants displayed observable attachment behavior that was classifiable. Nineteen VI infants showed attachment by 12 months of age. Across the ages tested (fractional age range = 0.9–2.33 months), most VI infants' attachment patterns were classified as secure and organized. [ABSTRACT FROM AUTHOR]

Objective: To examine the effects of a resistance-training program on athletes with intellectual disabilities (ID). Design/Participants: 2-way (2 × 2), repeated-measures analysis of variance on 2 groups (males and females); 30 Special Olympics (SO) athletes, age 16-22 (16 males, 14 females). Intervention/Outcome Measures: Resistance training, twice per week, for 3 months on Med-X weight equipment. Exercises tested: chest press, abdominal crunch, seated row, overhead press, seated dip, lower back extension, and biceps curl. The weight lifted and the number of repetitions performed were used to determine predicted 1-repetition max (1RM). Results: All participants as a group increased significantly in predicted 1RM for each exercise performed. Males were stronger than females for 5 of the 7 exercises. A significant interaction effect between genders was demonstrated for the seated dip. Conclusion: Significant strength gains can be accomplished by adolescents with ID via a supervised resistance-training program. [ABSTRACT FROM AUTHOR]

Direct-acting antivirals (DAA) have revolutionized the treatment of patients with chronic hepatitis C virus (HCV) infection, possibly leading to HCV elimination by 2030 as endorsed by the World Health Organization (WHO). However, some patients belonging to the so-called unique or special populations are referred to as difficult-to-treat due to unreached sustained virological response, potential drug side effects or interactions or co-morbidities. Several years after the DAA introduction and on the basis of excellent findings in terms of efficacy and safety, some doubts arise around the exact meaning of the special population designation and whether this group of patients actually exists. The aim of this review is to discuss and analyze current evidence on the management and treatment of the so-called “unique populations”. We placed particular emphasis on patients with decompensated cirrhosis, chronic kidney disease (CKD), coinfections, rare genotypes, and previous treatment failure, in order to provide physicians with an updated overview of the actual problems and needs in the current scenario.

Introduction We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. Methods We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. Results At entry, smoking prevalence was 15.4% in healthy participants, 29.8% with COPD, 15.8% with asthma, 21.7 % with diabetes mellitus, 17.2 % with ischemic heart disease/heart failure and 18.6% in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2% versus 27.7% in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95 % CI: 1.61–3.42), new diagnosis of asthma (OR=1.84, 95% CI: 1.18–2.90) and low number of pack-years. Conclusions Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support.

Background: This case study describes the implementation and evaluation of a multisite teen health information outreach program. The objectives of the program were to increase health knowledge, health information literacy, interest in health careers, community engagement, and leadership skills of teens in disadvantaged communities. Case Presentation: Teens at six sites across the country participated in a multi-week curriculum that focused on various aspects of health literacy, information literacy, and leadership. Lesson topics addressed personal health, social determinants of health, information quality, and communication and advocacy skills. Program evaluation included both quantitative and qualitative components and focused on multiple knowledge and skills outcome variables. Results suggested that while teens at all sites showed improvement, particularly with respect to engagement and interest in the topics, the degree of gains in knowledge and information literacy measures varied significantly from site to site. Conclusion: On-site implementation planning, cohesive integration of added activities, and emphasis on retention can contribute to implementation and evaluation effectiveness. This work also underscores the limitation of a purely quantitative approach to capturing the impact of health information and stresses the importance of supplementing numerical scores and statistics with qualitative data. This article has been approved for the Medical Library Association’s Independent Reading Program.

Anticoagulants are a cornerstone of treatment in atrial fibrillation. Nowadays, direct oral anticoagulants (DOACs) are extensively used for this condition in developed countries. However, DOAC treatment may be inappropriate in certain patient populations, such as: patients with chronic kidney disease in whom DOAC concentrations may be dangerously elevated; frail elderly patients with an increased risk of falls; patients with significant drug-drug interactions (DDI) affecting either DOAC concentration or effect; patients at the extremes of body mass in whom an "abnormal" volume of distribution may result in inappropriate drug concentrations; patients with recurrent stroke reflecting an unusually high thromboembolic tendency; and, lastly, patients who experience major hemorrhage on an anticoagulant and in whom continued anticoagulation is deemed necessary. Herein we provide a fictional case-based approach to review the recommendations for the use of DOACs in these special patient populations.

The introduction of direct-acting antiviral agents (DAAs) into clinical practice has revolutionized the therapeutic approach to patients with chronic hepatitis C virus (HCV) infection. According to the most recent guidelines, the first line of treatment for HCV infection involves the use of one of three pan-genotypic DAA combinations, sofosbuvir/velpatasvir (SOF/VEL), glecaprevir/pibrentasvir (GLE/PIB), and sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX). These drugs have been shown to be effective and safe in numerous clinical trials and real-world studies, but special populations have been neglected. Among the special populations to be treated are elderly patients, whose numbers are increasing in clinical practice. The management of these patients can be challenging, in particular due to multiple comorbidities, polypharmacotherapy, and potential drug-drug interactions. This narrative review aims to summarize the current scientific evidence on the efficacy and safety of DAAs in the elderly population, both in clinical trials and in real-life settings. Although there is still a paucity of real-world data and no clinical trials have yet been conducted in the population aged ≥ 75 years old, some considerations about the efficacy and safety of DAAs in the elderly can be made based on the results of these studies. The pan-genotypic associations of DAAs appear to be as efficacious and safe in the elderly population as in the general population; this is both in terms of similar sustained virologic response (SVR) rates and similar frequencies of adverse events (AEs). However, further studies specifically involving this patient population would be necessary to confirm this evidence.

INTRODUCTION We examined changes in smoking habits in the general population according to prevalence and incidence of chronic diseases affected by smoking. METHODS We included 12283 individuals enrolled from 2003 in the Copenhagen General Population Study and re-examined from 2014. Participants were classified as either healthy or suffering from chronic obstructive pulmonary disease (COPD), asthma, diabetes mellitus, heart disease or stroke. RESULTS At entry, smoking prevalence was 15.4% in healthy participants, 29.8% with COPD, 15.8% with asthma, 21.7 % with diabetes mellitus, 17.2 % with ischemic heart disease/heart failure and 18.6% in participants with previous stroke. Smoking prevalence declined during the 10 years of observation. Among healthy subjects who developed one of the above mentioned diseases during follow-up, those who developed COPD had the highest initial smoking prevalence (51.5%). Quit rates were highest in those who developed asthma resulting in smoking prevalence of 8.2% versus 27.7% in COPD. After adjustment for age, smoking severity and genotype previously associated with heavy smoking (CHRNA3 rs1051730 AA), significant predictors of quitting were new diagnosis of ischemic heart disease/heart failure (OR=2.33, 95 % CI: 1.61–3.42), new diagnosis of asthma (OR=1.84, 95% CI: 1.18–2.90) and low number of pack-years. CONCLUSIONS Individuals with prevalent smoking related diseases continued to smoke more than healthy individuals. Incident heart disease and asthma, but not incident COPD, stroke or diabetes were associated with a higher chance of quitting. Special focus on smokers with COPD, asthma, diabetes, stroke and ischemic heart disease/heart failure is warranted to decrease smoking prevalence in these groups. Smokers with a new diagnosis of diabetes, stroke and COPD need special smoking cessation support. [ABSTRACT FROM AUTHOR]

Biologics, especially monoclonal antibodies, are increasingly important in the pharmaceutical marketplace. Population pharmacokinetic (PK) analyses could be useful to guide the need for dose adjustments among special populations, yet it is unknown how commonly such analyses are performed during biologics development. We summarized the characteristics of population PK models of biologics and examined their role in informing the drug labels. To do so, we extracted relevant characteristics of 86 biologics approved by the U.S. Food and Drug Administration's Center for Drug Evaluation and Research between 2003 and 2017. Ninety‐four percent of monoclonal antibodies (51 of 54 biologics), 75% of fusion proteins with Fc receptor (6 of 8 biologics), and 33% of other proteins (8 of 24 biologics) included population PK analyses. Of these analyses, approximately half (45%) used a 2‐compartment model with linear clearance as the base model structure. Body size was the most frequently included covariate in the final models (included in 94% of the 64 biologics in which covariate analysis was performed), although age (11%), sex (35%), race (26%), and renal function (27%) were also included in some models. In 70% to 90% of cases in which the effect of these covariates was examined, information regarding the effect of these on PK was included in the label. These results suggest that population PK analyses provide important information about the impact of intrinsic factors on the PK in the label of biologics by the U.S. Food and Drug Administration. [ABSTRACT FROM AUTHOR]

ACHILLES TENDINOPATHY (AT) IS A CONDITION WHEREBY INDIVIDUALS EXPERIENCE PAIN AND IMPAIRMENTS AS A RESULT OF PATHOLOGICAL CHANGES AT THE ACHILLES TENDON AND NEIGHBORING TISSUES. THIS ARTICLE PROVIDES AN EVIDENCE-BASED OVERVIEW OF THE STRUCTURAL PATHOLOGY AND CLINICAL SEQUELA ASSOCIATED WITH AT. THE EVIDENCE UNDERPINNING MORE COMMON TREATMENTS, WITH AN EMPHASIS ON EXERCISE INTERVENTIONS, IS PRESENTED IN AN EFFORT TO MITIGATE THE IMPAIRMENT SEQUELA AND GUIDE SPORTS MEDICINE PROFESSIONALS IN THEIR CHOICE OF TREATMENTS FOR AT. [ABSTRACT FROM AUTHOR]

EVALUATING AND IMPROVING THE PERFORMANCE OF ACTIVITIES OF DAILY LIVING IS OF PARAMOUNT IMPORTANCE TO MAINTAINING THE LONG-TERM PHYSICAL CAPABILITY OF INDIVIDUALS WITH HUNTINGTON'S DISEASE (HD). BECAUSE MOST PHARMACOLOGIC AND PSYCHIATRIC TREATMENTS FOR HD ARE FOCUSED ON THE MANAGEMENT OF SIGNS AND SYMPTOMS OF THE DISEASE RATHER THAN DELAYING PROGRESSIVE ONSET OF CLINICAL MANIFESTATION, EXERCISE INTERVENTIONS MAY BE A PROMISING SOLUTION TO PROVIDE BENEFICIAL IMPROVEMENTS IN FUNCTIONAL CAPACITY AND NEUROMOTOR FUNCTION WHILE DELAYING CARE DEPENDENCY. [ABSTRACT FROM AUTHOR]

Drug product labels are important vehicles for conveying the scientific information needed for the safe and effective use of a medicinal product. Increasingly, pharmacogenomic (PGx) information is being incorporated into US Food and Drug Administration‐approved product labels. In the majority of cases, the PGx information in labeling is derived from studies in adults. Observed genotype‐phenotype relationships in adults may not always be reflective of those in certain pediatric age groups because of the influence of ontogeny. The quantitative data necessary for modeling certain genomic markers in pediatrics is still lacking, and further research focused on generating this is needed. In addition, drug safety research focused on understanding the potential contributions of ontogeny, PGx and other underlying mechanisms to differences in adverse drug reactions between pediatrics and adults is warranted. [ABSTRACT FROM AUTHOR]

Abstract Physiologically-based pharmacokinetic (PBPK) models provide a framework for in vitro-in vivo extrapolation of metabolic drug clearance. Many of the concepts in PBPK can have consequential impact on more mechanistic systems pharmacology models. In the gut wall, turnover of enzymes and enterocytes are typically lumped into one rate constant that describes the time dependent enzyme activity. This assumption may influence predictability of any sustained and dynamic effects such as mechanism-based inhibition (MBI), particularly when considering translation from healthy to gut disease. A novel multi-level systems PBPK model was developed. This model comprised a 'nested enzyme-within enterocyte' (NEWE) turnover model to describe levels of drug-metabolising enzymes. The ability of the model to predict gut metabolism following MBI and gut disease was investigated and compared to the conventional modelling approach. For MBI, the default NEWE model performed comparably to the conventional model. However, when drug-specific spatial crypt-villous absorption was considered, up to approximately 50% lower impact of MBI was simulated for substrates highly metabolised by cytochrome P450 (CYP) 3A4, interacting with potent inhibitors. Further, the model showed potential in predicting the disease effect of gastrointestinal mucositis and untreated coeliac disease when compared to indirect clinical pharmacokinetic parameters. Considering the added complexity of the NEWE model, it does not provide an attractive solution for improving upon MBI predictions in healthy individuals. However, nesting turnover may enable extrapolation to gut disease-drug interactions. The principle detailed herein may be useful for modelling drug interactions with cellular targets where turnover is significant enough to affect this process. Graphical abstract Unlabelled Image [ABSTRACT FROM AUTHOR]

During the past two decades, a range of in vitro models simulating the digestion processes occurring in the stomach and small intestine have been developed to characterize lipid based drug delivery systems (LbDDSs). This review describes the presently existing range of in vitro digestion models and their use in the field of oral drug delivery. The models are evaluated in terms of their suitability to assess LbDDSs, and their ability to produce in vitro - in vivo correlations (IVIVCs). While the pH-stat lipolysis model is by far the most commonly utilized in vitro digestion model in relation to characterizing LbDDSs, a series of recent studies have shown a lack of IVIVCs limiting its future use. Presently, no single in vitro digestion model exists which is able to predict the in vivo performance of various LbDDSs. However, recent research has shown the potential of combined digestion-permeation models as well as species specific digestion models. Unlabelled Image [ABSTRACT FROM AUTHOR]