Gender-affirming pharmacotherapy and additional health considerations: A contemporary review.

BACKGROUND: Transgender and gender-diverse (TGD) individuals in the United States face health care disparities compounded with discrimination and limited access to necessary medical services. Gender-affirming interventions have been shown to mitigate gender dysphoria and psychiatric comorbidities, yet United States legislation limiting such interventions has increased. As medication experts, pharmacists can facilitate access to care and appropriate use of gender-affirming hormone therapy (GAHT) and educate other health care providers on best practices for caring for TGD individuals in a variety of settings. OBJECTIVES: To provide pharmacists with a contemporary review of GAHT and associated medication-related concerns. METHODS: We searched PubMed for articles published until December 2022. MeSH terms such as transgender, transsexual, gender diverse, gender variant, or gender nonconforming in combination with phrases like gender-affirming care, treatment, pharmacotherapy, or hormone therapy were used to capture desired articles. RESULTS: Feminizing hormone therapy (FHT), such as estrogen and antiandrogen agents, increases female secondary sex characteristics while suppressing male secondary sex characteristics. Masculinizing hormone therapy (MHT) achieves male secondary sex characteristics and minimizes female secondary sex characteristics using testosterone. For both FHT and MHT, the choice of therapy and formulation ultimately involves the patient's treatment goals, preferences, and tolerability. GAHT has additional health considerations pertaining to renal drug dosing, fertility, cardiovascular, and cancer risks. Pharmacists may provide crucial guidance and education to both patients and health care providers regarding risks associated with GAHT. CONCLUSION: Many pharmacists feel unprepared to help provide, manage, and optimize GAHT. For many TGD individuals, GAHT is medically necessary and a life-saving treatment. Therefore, pharmacists should be provided tools to close knowledge gaps and improve their ability to care for these patients. By offering a thorough updated overview of GAHT, pharmacists can gain confidence to provide appropriate care for this increasingly visible population.

How gaps in regulation of compounding pharmacy set the stage for a multistate fungal meningitis outbreak.

OBJECTIVE: To provide an overview of the regulation issues surrounding compounding pharmacy that allowed the United States fungal meningitis outbreak to occur and the changes in regulation that ensued. SUMMARY: In September 2012, a single case report sparked an investigation into a nationwide outbreak of fungal meningitis due to contaminated injectable drugs. The source of the contamination, New England Compounding Center (NECC), was in violation of several state and federal laws and had a history of such violations. The regulation of compounding pharmacies has historically been left to the states, while manufacturing fell under the jurisdiction of the Food and Drug Administration. However, as more compounders took part in large-scale interstate distribution of drugs, the current state-based regulatory system became less equipped to provide oversight. The lack of a clear definition of "compounding pharmacy" further obscures proper oversight and regulation. Congress and several states have taken steps to build safeguards against large-scale compounding by increasing inspections, adopting stricter licensing requirements, and enacting the Drug Quality and Security Act of 2013. CONCLUSION: While the current compounding regulation changes are a necessary step forward, it remains to be seen how effective they will be in safeguarding the public.

Differences in national antiretroviral prescribing patterns between black and white patients with HIV/AIDS, 1996-2006.

OBJECTIVES: The benefit of improved health outcomes for blacks receiving highly active antiretroviral therapy (HAART) lags behind that of whites. This project therefore sought to determine whether the reason for this discrepancy in health outcomes could be attributed to disparities in use of antiretroviral therapy between black and white patients with HIV. MATERIALS AND METHODS: The 1996-2006 National Hospital Ambulatory Medical Care Surveys were used to identify hospital outpatient visits that documented antiretrovirals. Patients younger than 18 years, of nonblack or nonwhite race, and lacking documentation of antiretrovirals were excluded. A multivariable logistic regression model was constructed with race as the independent variable and use of HAART as the dependent variable. RESULTS: Approximately 3 million HIV/AIDS patient visits were evaluated. Blacks were less likely than whites to use HAART and protease inhibitors (odds ratio, 95% CI 0.81 [0.81-0.82] and 0.67 [0.67-0.68], respectively). More blacks than whites used non-nucleoside reverse transcriptase inhibitors (odds ratio, 95% CI 1.18 [1.17-1.18]). In 1996, the crude rates of HAART were relatively low for both black and white cohorts (5% vs 6%). The rise in HAART for blacks appeared to lag behind that of whites for several years, until 2002, when the proportion of blacks receiving HAART slightly exceeded the proportion of whites receiving HAART. In later years, the rates of HAART were similar for blacks and whites (81% vs 82% in 2006). Blacks appeared less likely than whites to use protease inhibitors and more likely than whites to use non-nucleoside reverse transcriptase inhibitors from 2000 to 2004. CONCLUSIONS: Blacks experienced a lag in the use of antiretrovirals at the beginning of the study; this discrepancy dissipated in more recent years.

Gut microbiome differences among Mexican Americans with and without type 2 diabetes mellitus.

PURPOSE: Type 2 diabetes mellitus (T2DM) is an urgent public health problem and disproportionately affects Mexican Americans. The gut microbiome contributes to the pathophysiology of diabetes; however, no studies have examined this association in Mexican-Americans. The objective of this study was to compare gut microbiome composition between Mexican-Americans with and without T2DM. METHODS: This was a cross-sectional study of volunteers from San Antonio, TX. Subjects were 18 years or older and self-identified as Mexican American. Subjects were grouped by prior T2DM diagnosis. Eligible subjects attended a clinic visit to provide demographic and medical information. Thereafter, subjects recorded their dietary intake for three days and collected a stool sample on the fourth day. Stool 16s rRNA sequences were classified into operational taxonomic units (OTUs) via the mothur bayesian classifier and referenced to the Greengenes database. Shannon diversity and bacterial taxa relative abundance were compared between groups using the Wilcoxon rank sum test. Beta diversity was estimated using Bray-Curtis indices and compared between groups using PERMANOVA. RESULTS: Thirty-seven subjects were included, 14 (38%) with diabetes and 23 (62%) without diabetes. Groups were well-matched by body mass index and comorbid conditions. Shannon diversity was not significantly different between those with and without T2DM (3.26 vs. 3.31; p = 0.341). Beta diversity was not significantly associated with T2DM diagnosis (p = 0.201). The relative abundance of the most common bacterial phyla and families did not significantly differ between groups; however, 16 OTUs were significantly different between groups. CONCLUSIONS: Although alpha diversity was not significantly different between diabetic and non-diabetic Mexican Americans, the abundance of certain bacterial taxa were significantly different between groups.

Black race as a predictor of poor health outcomes among a national cohort of HIV/AIDS patients admitted to US hospitals: a cohort study.

BACKGROUND: In general, the Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) population has begun to experience the benefits of highly active antiretroviral therapy (HAART); unfortunately, these benefits have not extended equally to Blacks in the United States, possibly due to differences in patient comorbidities and demographics. These differences include rates of hepatitis B and C infection, substance use, and socioeconomic status. To investigate the impact of these factors, we compared hospital mortality and length of stay (LOS) between Blacks and Whites with HIV/AIDS while adjusting for differences in these key characteristics. METHODS: The 1996-2006 National Hospital Discharge Surveys were used to identify HIV/AIDS patients admitted to US hospitals. Survey weights were incorporated to provide national estimates. Patients < 18 years of age, those who left against medical advice, those with an unknown discharge disposition and those with a LOS < 1 day were excluded. Patients were stratified into subgroups by race (Black or White). Two multivariable logistic regression models were constructed with race as the independent variable and outcomes (mortality and LOS > 10 days) as the dependent variables. Factors that were significantly different between Blacks and Whites at baseline via bivariable statistical tests were included as covariates. RESULTS: In the general US population, there are approximately 5 times fewer Blacks than Whites. In the present study, 1.5 million HIV/AIDS hospital discharges were identified and Blacks were 6 times more likely to be hospitalized than Whites. Notably, Blacks had higher rates of substance use (30% vs. 24%; P < 0.001), opportunistic infections (27% vs. 26%; P < 0.001) and cocaine use (13% vs. 5%; P < 0.001). Conversely, fewer Blacks were co-infected with hepatitis C virus (8% vs. 12%; P < 0.001). Hepatitis B virus was relatively infrequent (3% for both groups). Crude mortality rates were similar for both cohorts (5%); however, a greater proportion of Blacks had a LOS > 10 days (21% vs. 19%; P < 0.001). Black race, in the presence of comorbidities, was correlated with a higher odds of LOS > 10 days (OR, 95% CI = 1.20 [1.10-1.30]), but was not significantly correlated with a higher odds of mortality (OR, 95% CI = 1.07 [0.93-1.25]). CONCLUSION: Black race is a predictor of LOS > 10 days, but not mortality, among HIV/AIDS patients admitted to US hospitals. It is possible that racial disparities in hospital outcomes may be closing with time.

Disparities in antiretroviral prescribing for blacks and whites in the United States.

PURPOSE: The health benefits for blacks on highly active antiretroviral therapy (HAART) lags behind that of whites. We therefore investigated whether this discrepancy in health outcomes is attributable to disparities in the receipt of appropriate HAART between black and white human immunodeficiency virus (HIV) patients. METHODS: The 2000-2005 National Ambulatory Medical Care Surveys were used to identify patients receiving antiretrovirals. Regimens were evaluated for appropriateness according to national antiretroviral guideline recommendations. A multivariable logistic regression model was used to assess black race as a predictor for appropriate HAART. RESULTS: An estimated 4.1 million HIV-related visits with antiretroviral therapy were identified. Eighty-six percent of visits were associated with appropriate therapy; inappropriate therapy was often due to antiretroviral monotherapy. Interestingly, blacks were more likely to receive appropriate therapy in comparison to white patients (94% vs 83%, P < .001). Multivariable analysis revealed black race as an independent predictor for an appropriate regimen (chi2 likelihood ratio, 12.3, P < .001) when controlling for age, gender, insurance status, and geographic region. CONCLUSIONS: Health outcome disparities between black and white HIV patients do not appear to be attributable to differences in receipt of appropriate HAART. Further investigations are warranted to identify factors responsible for these outcome disparities.

Evaluating HIV/AIDS disparities for blacks in the United States: a review of antiretroviral and mortality studies.

The purpose of this systematic review was to identify studies that evaluated HIV/AIDS disparities by examining differences in the receipt of antiretroviral therapy and differences in mortality between blacks and whites in the United States. The authors conducted 2 Web-based literature searches of the MEDLINE database for published peer reviewed scientific articles that analyzed black race as a predictor of antiretroviral therapy and mortality. Five reports met the criteria for the antiretroviral literature search, whereas seven reports met the criteria for the mortality literature search. After evaluating individual study results, it appears the evidence to identify racial differences in the receipt of antiretroviral therapy as well as the evidence to document disparities in mortality is either limited or mixed. Further research is needed to support or refute the hypothesis that there are inequalities for blacks with HIV/AIDS.

HIV/AIDS disparities: the mounting epidemic plaguing US blacks.

The human immunodeficiency virus (HIV)/AIDS epidemic presents a formidable challenge for the black community. Blacks, although a small proportion of the US population, are overrepresented, not only in the number of people living with HIV, but also in the categories of new diagnoses and AIDS-related deaths. Fortunately, national initiatives are in place to slow and ultimately reverse these racial inequities. While these disparities may be widely recognized, their causes are not clearly understood. A variety of underlying issues exist for blacks in the United States that may also contribute to these growing disparities. These include transmission risk factors, socioeconomic factors, underrecognition, delayed presentation, and other comorbid conditions. We present a review of the literature regarding the potential causes of racial disparities and how they may contribute to health outcomes for blacks with HIV/AIDS in the United States. We also identify possible gaps in knowledge and offer future directions for research of HIV/AIDS racial disparities.

National ambulatory care non-insulin antidiabetic medication prescribing trends in the United States from 2009 to 2015.

OBJECTIVE: Despite their efficacy in lowering hemoglobin A1c, recent data suggest that sulfonylureas are associated with cardiovascular risk and hypoglycemia. The objective of this study was to determine whether prescribers decreased sulfonylurea use in favor of newer medications in the United States over seven years. RESEARCH DESIGN AND METHODS: This cross-sectional study utilized data from the Centers for Disease Control and Prevention's National Ambulatory Medical Care Survey. Patient visits between 2009 and 2015 were included for patients who were at least 18 years old, had a documented prescription for a non-insulin antidiabetic medication, and a diagnosis of type 2 diabetes. Sample survey data were extrapolated to national estimates using data weights. Prescribing rates were calculated as the number of visits with a documented medication class divided by the total number of visits with a prescription for any diabetes medication class, times 100%. RESULTS: A total of 303 million patient visits were included in this study. The median (IQR) patient age was 64 (55-73) years old and 49.8% were male. Sulfonylurea prescribing rates decreased from 43% in 2009 to 36.5% in 2015. Prescribing of GLP-1 receptor agonists increased from 2009 to 2014 (3.95% to 5.30%), but then decreased to 4.19% in 2015. SGLT-2 inhibitor prescribing began in 2013 and increased to 7.3% by 2015. Metformin prescribing remained relatively stable over the study period (range 70% to 72%). CONCLUSIONS: National ambulatory sulfonylurea prescribing decreased from 2009 to 2015 with a corresponding increase in newer non-insulin antidiabetic agent prescribing.

Age-based health and economic burden of skin and soft tissue infections in the United States, 2000 and 2012.

OBJECTIVE: The aim of this study was to compare the incidence of skin and soft tissue infections (SSTIs) across healthcare settings and analyze direct healthcare expenditures related to SSTIs in 2000 and 2012 in the United States. METHODS: We performed a retrospective, cross-sectional analysis of nationally representative data from the Medical Expenditure Panel Surveys. Population-based incidence rates were examined for all healthcare settings that include inpatient visits, emergency department visits and ambulatory visits for SSTIs. The direct costs of healthcare services utilization were reported. Population-based prescribing rates for each antimicrobial class during ambulatory visits were compared. RESULTS: A total of 2.4 million patients experienced an SSTI in 2000 compared to 3.3 million in 2012 (40% increase). From 2000 to 2012, the incidence of patients with at least one hospital visit for SSTIs increased 22%, ambulatory care visits increased 30%, and emergency department visits increased 40%. The incidence of SSTIs in children and adolescents declined 50% (from 150 to 76 per 10,000 person; RR = 0.51, 95% CI: 0.38-0.67; p<0.001) whereas SSTIs in older adults (> 65 years of age) increased almost 2-fold (from 67 to 130 per 10,000 person; RR = 1.94, 95% CI: 1.44-2.61; p<0.001). The annual incidence of SSTI in adults did not change significantly from 2000 to 2012 (from 84 to 81 per 10,000 person; RR = 0.96, 95% CI: 0.71-1.31; p = 0.41). The total estimated direct healthcare costs of SSTIs increased 3-fold from $4.8 billion in 2000 to $15.0 billion in 2012, largely driven by an 8-fold increase in ambulatory expenditures for SSTIs. Total population-based antimicrobial prescription rates for SSTIs increased 4-fold from 2000 to 2012 (from 59.5 to 250.4 per 10,000 person). CONCLUSIONS: The highest healthcare utilization for SSTI treatment occurred in the ambulatory care setting and also accounted for the largest increase in overall direct expenditures from 2000 to 2012.

Health care-associated pneumonia in the intensive care unit: Guideline-concordant antibiotics and outcomes.

PURPOSE: Recent data have not demonstrated improved outcomes when guideline-concordant (GC) antibiotics are given to patients with health care-associated pneumonia (HCAP). This study was designed to evaluate the relationship between health outcomes and GC therapy in patients admitted to an intensive care unit (ICU) with HCAP. MATERIALS AND METHODS: We performed a population-based cohort study of patients admitted to greater than 150 hospitals in the US Veterans Health Administration system to compare baseline characteristics, bacterial pathogens, and health outcomes in ICU patients with HCAP receiving GC-HCAP therapy, GC community-acquired pneumonia (GC-CAP) therapy, or non-GC therapy. The primary outcome was 30-day patient mortality. Risk factors for the primary outcome were assessed in a multivariable logistic regression model. RESULTS: A total of 3593 patients met inclusion criteria and received GC-HCAP therapy (26%), GC-CAP therapy (23%), or non-GC therapy (51%). Patients receiving GC-HCAP had higher 30-day patient mortality compared to GC-CAP patients (34% vs 22%; P< .0001). After controlling for confounders, risk factors for 30-day patient mortality were vasopressor use (odds ratio, 1.67; 95% confidence interval, 1.30-2.13), recent hospital admission (1.53; 1.15-2.02), and receipt of GC-HCAP therapy (1.51; 1.20-1.90). CONCLUSIONS: Our data do not demonstrate improved outcomes among ICU patients with HCAP who received GC-HCAP therapy.

Fenofibrate-associated nephrotoxicity: a review of current evidence.

PURPOSE: The literature describing fenofibrate-associated nephrotoxicity was reviewed. SUMMARY: Fenofibrate-associated nephrotoxicity is an underrecognized adverse effect that is being reported with increasing frequency in the medical literature. A MEDLINE search identified articles describing fenofibrate-associated nephrotoxicity. Two retrospective chart reviews reported this adverse reaction in transplant recipients and patients with renal insufficiency. A case series of six patients noted that the adverse reaction also occurred in patients without a predisposition to renal injury. Two small prospective studies have examined fenofibrate-associated nephrotoxicity, with conflicting findings regarding the mechanism. Finally, a large retrospective review and a population-based cohort study found that patients with preexisting renal disease or taking high-dosage fenofibrate have a higher risk of developing fenofibrate-associated nephrotoxicity. Fenofibrate-associated nephrotoxicity was shown to be reversible with both discontinuation and continued use of fenofibrate, though one study found that the elevations in serum creatinine (SCr) levels were permanent in study participants. Some argue that SCr elevations described in these articles were not due to renal toxicity but may be attributed to reversible mechanisms. While several mechanisms may be biologically plausible, none of the theories have been tested in clinical trials. A possible mechanism for the increase in SCr levels may include changes in renal hemodynamics causing volume depletion and the impairment of generation of vasodilatory prostaglandins, leading to renal vasoconstriction. CONCLUSION: Fenofibrate-associated nephrotoxicity is an underrecognized adverse drug reaction. Several published reports have detailed possible etiologies; however, data detailing the true incidence of fenofibrate-associated nephrotoxicity and its associated risk factors are limited.

Evaluation of the incidence and risk factors for development of fenofibrate-associated nephrotoxicity.

BACKGROUND: Fenofibrate-associated nephrotoxicity has been described in two randomized controlled trials and several observational studies. However, little is known regarding its incidence and the population(s) at risk. OBJECTIVE: This study aims to quantify the incidence and identify potential risk factors for development of nephrotoxicity in patients receiving fenofibrate. METHODS: A retrospective, observational study was conducted in the South Texas Veterans Health Care System. Data were collected regarding baseline demographics, concurrent medical conditions, medications, laboratory results, and fenofibrate use. RESULTS: Within 6 months after initiation of fenofibrate in 428 patients, 115 (27%) experienced an increase in serum creatinine of ≥ 0.3 mg/dL. Any renal disease (P = .001), chronic kidney disease (P = .01), and diabetes (P = .02) were significantly more prevalent in patients with fenofibrate-associated nephrotoxicity. Patients with nephrotoxicity had significantly greater serum creatinine (1.2 [SD 0.3] vs. 1.1 mg/dL [SD 0.3], P = .0002) and lower estimated glomerular filtration rate (72 [SD 20] vs 81 mL/min/1.73 m² [SD 20], P < .0001) at baseline. These patients also had greater use of calcium channel blockers (P = .0003), furosemide (P = .02), and angiotensin-converting enzyme inhibitors (P = .02). The incidence of nephrotoxicity was significantly greater in patients initiated on high-dose versus those on low-dose fenofibrate (P = .002). In a multivariable regression model, renal disease (P = .02), high-dose fenofibrate (P = .001), and dihydropyridine calcium channel blocker use (P = .02) were determined to be independent predictors of development of increased serum creatinine on fenofibrate. CONCLUSION: This observational study suggests fenofibrate-associated nephrotoxicity occurs more frequently than previously reported, particularly in patients with renal disease and in those receiving high-dose fenofibrate or concomitant calcium channel blockers.

Antibacterials as adjuncts to incision and drainage for adults with purulent methicillin-resistant Staphylococcus aureus (MRSA) skin infections.

The annual incidence of skin and soft tissue infections (SSTIs) has nearly tripled in the US since the early 1990s. Many purulent SSTIs in the community setting are caused by methicillin-resistant Staphylococcus aureus (MRSA). Incision and drainage (I&D) are indicated for most purulent MRSA infections; however, the use of adjunctive antibacterials is controversial. The objective of this study was to systematically evaluate studies that have investigated whether or not antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs. We included articles from MEDLINE and The Cochrane Library that fulfilled the following criteria: (i) original research; (ii) English language; (iii) compared I&D alone versus I&D plus antibacterials for purulent MRSA SSTIs; and (iv) compared patient outcomes. We also reviewed the references of these articles to identify other relevant studies. Studies that solely examined paediatric patients were excluded. To facilitate cross-study comparison, we systematically evaluated the following study characteristics: (i) study design; (ii) patient population; (iii) comparator groups; (iv) sample size; (v) outcome measures; (vi) outcome definitions; (vii) duration of follow-up; and (viii) measurement and adjustment of potential confounding variables. Eleven studies, spanning more than 30 years, met inclusion criteria. Two of these were conducted prior to the emergence of MRSA in the community; another evaluated cephalexin versus placebo for MRSA. None of these found added benefit of adjunctive antibacterials. Four studies compared health outcomes between patients who received 'active' or 'appropriate' therapy and those who received 'inactive' or 'inappropriate' therapy after I&D for purulent MRSA SSTIs. Two of these studies found 'active' or 'appropriate' therapy to be beneficial, while two others did not. Four studies compared health outcomes between patients who received anti-MRSA antibacterials plus I&D with those who received alternative antibacterials plus I&D for purulent MRSA SSTIs. Three of these reported improved outcomes with anti-MRSA antibacterials, while another reported mixed findings. Presently, the bulk of the available evidence suggests anti-MRSA antibacterials provide added benefit to I&D alone for purulent MRSA SSTIs; however, the current evidence is limited to small, case-control, observational studies.

How low should you go? The limbo of glycemic control in intensive care units.

Hyperglycemia, a common finding in critically ill patients, is linked to poor outcomes in multiple conditions. The Leuven I study published in 2001 was the first evaluation of intensive insulin therapy, and the 3.4% absolute reduction in mortality in a single-center surgical intensive care unit led to widespread endorsement of the therapy. In a subsequent study in a medical intensive care unit, reduction in mortality was not significant. Two multicenter studies were stopped early because of significantly higher rates of hypoglycemia in the patients receiving intensive insulin therapy. The episodes of hypoglycemia were linked to increased mortality. In the largest prospective study conducted to date, mortality was significantly higher (P = .02) in patients who had intensive therapy (27.5%) than in control patients (24.9%). Thus, after years of research, intensive insulin therapy does not appear to convey the original benefit in all critically ill patients. Several organizations have proposed alternative blood glucose targets, such as 140 to 180 mg/dL, to both provide glycemic control and reduce the opportunity for hypoglycemic episodes.