With the adoption of combination antiretroviral therapy (ART), most HIV-infected individuals in care are on five or more medications and at risk of harm from polypharmacy, a risk that likely ...increases with number of medications, age, and physiologic frailty. Established harms of polypharmacy include decreased medication adherence and increased serious adverse drug events, including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline) and mortality. The literature on polypharmacy among those with HIV infection is limited, and the literature on polypharmacy among non-HIV patients requires adaptation to the special issues facing those on chronic ART. First, those aging with HIV infection often initiate ART in their 3rd or 4th decade of life and are expected to remain on ART for the rest of their lives. Second, those with HIV may be at higher risk for age-associated comorbid disease, further increasing their risk of polypharmacy. Third, those with HIV may have an enhanced susceptibility to harm from polypharmacy due to decreased organ system reserve, chronic inflammation, and ongoing immune dysfunction. Finally, because ART is life-extending, nonadherence to ART is particularly concerning. After reviewing the relevant literature, we propose an adapted framework with which to address polypharmacy among those on lifelong ART and suggest areas for future work.
BACKGROUNDThe role of potentially inappropriate medications (PIMs) in mortality has been studied among those 65 years or older. While middle-aged individuals are believed to be less susceptible to ...the harms of polypharmacy, PIMs have not been as carefully studied in this group.OBJECTIVETo estimate PIM-associated risk of mortality and evaluate the extent PIMs explain associations between polypharmacy and mortality in middle-aged patients, overall and by sex and race/ethnicity.DESIGNObservational cohort study.SETTINGDepartment of Veterans Affairs (VA), the largest integrated healthcare system in the US.PARTICIPANTSPatients aged 41 to 64 who received a chronic medication (continuous use of ≥ 90 days) between October 1, 2008, and September 30, 2017.MEASUREMENTPatients were followed for 5 years until death or end of study period (September 30, 2019). Time-updated polypharmacy and hyperpolypharmacy were defined as 5-9 and ≥ 10 chronic medications, respectively. PIMs were identified using the Beers criteria (2015) and were time-updated. Cox models were adjusted for demographic, behavioral, and clinical characteristics.RESULTSOf 733,728 patients, 676,935 (92.3%) were men, 479,377 (65.3%) were White, and 156,092 (21.3%) were Black. By the end of follow-up, 104,361 (14.2%) patients had polypharmacy, 15,485 (2.1%) had hyperpolypharmacy, and 129,992 (17.7%) were dispensed ≥ 1 PIM. PIMs were independently associated with mortality (HR 1.11, 95% CI 1.04-1.18). PIMs also modestly attenuated risk of mortality associated with polypharmacy (HR 1.07, 95% CI 1.03-1.11 before versus HR 1.05, 95% CI 1.01-1.09 after) and hyperpolypharmacy (HR 1.18, 95% CI 1.09-1.28 before versus HR 1.12, 95% CI 1.03-1.22 after). Patterns varied when stratified by sex and race/ethnicity.LIMITATIONSThe predominantly male VA patient population may not represent the general population.CONCLUSIONPIMs were independently associated with increased mortality, and partially explained polypharmacy-associated mortality in middle-aged people. Other mechanisms of injury from polypharmacy should also be studied.
Objective
Medical intensive care unit (MICU) admissions have been declining in people with HIV infection (PWH), but frequency of outpatient polypharmacy (prescription of ≥5 chronic medications) has ...increased. Among those hospitalized, we examined whether outpatient polypharmacy is associated with subsequent 1-year MICU admission or 10-year all-cause mortality, and if the association varies by HIV status.
Design
Retrospective cohort study.
Methods
Using a national electronic health record cohort of Veterans in care, we ascertained outpatient polypharmacy during fiscal year (FY) 2009 and followed patients for 1-year MICU admission and 10-year mortality. We assessed associations of any polypharmacy (yes/no and categorized ≤4, 5–7, 8–9, and ≥10 medications) with 1-year MICU admission and 10-year mortality using logistic and Cox regressions, respectively, adjusted for demographics, HIV status, substance use, and severity of illness.
Results
Among 9898 patients (1811 PWH) hospitalized in FY2010, prior outpatient polypharmacy was common (51%). Within 1 year, 1532 (15%) had a MICU admission and within 10 years, 4585 (46%) died. Polypharmacy was associated with increased odds of 1-year MICU admission, in both unadjusted (odds ratio (OR) 1.36 95% CI: (1.22, 1.52)) and adjusted models, aOR (95% CI) = 1.28 (1.14, 1.43) and with 10-year mortality in unadjusted, hazard ratio (HR) (95% CI) = 1.40 (1.32, 1.48), and adjusted models, HR (95% CI) = 1.26 (1.19, 1.34). Increasing levels of polypharmacy demonstrated a dose-response with both outcomes and by HIV status, with a stronger association among PWH.
Conclusions
Among hospitalized patients, prior outpatient polypharmacy was associated with 1-year MICU admission and 10-year all-cause mortality after adjusting for severity of illness in PWH and PWoH.
The current wars in Iraq and Afghanistan have led to an increasing number of female veterans seeking medical and mental healthcare in the Department of Veterans Affairs (VA) healthcare system. To ...better understand gender differences in healthcare needs among recently returned veterans, we examined the prevalence of positive screenings for depression, posttraumatic stress disorder (PTSD), military sexual trauma (MST), obesity, and chronic pain among female and male veterans of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) receiving care at the VA Connecticut Healthcare System.
We performed a retrospective, cross-sectional data analysis of OEF/OIF veterans at VA Connecticut who received services in either Primary Care or the Women's Health Clinic between 2001 and 2006.
In this study, 1129 electronic medical records (1032 men, 197 women) were examined. Female veterans were more likely to screen positive for MST (14% vs. 1%, p < 0.001) and depression (48% vs. 39%, p = 0.01) and less likely to screen positive for PTSD (21% vs. 33%, p = 0.002). There was no significant gender difference in clinically significant pain scores. Men were more likely than women to have body mass index (BMI) >30 kg/m(2) (21% vs. 13%, p = 0.008).
These results suggest that important gender differences exist in the prevalence of positive screenings for MST, depression, obesity, and PTSD. As the VA continues to review and improve its services for women veterans, clinicians, researchers, and senior leaders should consider innovative ways to ensure that female veterans receive the health services they need within the VA system.
Abstract
Objective
Pain is one of the most significant causes of morbidity and disability worldwide. The efficacy of several nonpharmacological approaches for pain management has been established, ...but significant gaps exist between this evidence and their limited availability and use in routine clinical practice. Questions remain about their effectiveness and how best to integrate them in usual care to optimize patient-centered outcomes. Pragmatic clinical trials (PCTs) may help address this gap. Informed by the Pragmatic Explanatory Continuum Indicator Summary (PRECIS-2), we sought to describe the key features of optimized PCTs of nonpharmacological approaches for the management of pain and common co-occurring conditions.
Methods
To accomplish this objective, we searched the published literature on PCTs of nonpharmacological pain management approaches from 2010–2019 and applied the PRECIS-2 criteria. We discuss key PRECIS-2 domains of interest for designing and performing PCTs and cite specific examples from the published literature as potential models for future PCTs.
Results
We found 13 nonpharmacological PCTs. They were heterogeneous in size, recruitment, follow-up time, and location. The lessons learned from these studies led us to explicate key features of trials on the explanatory–pragmatic continuum across the PRECIS-2 domains that can be used by future investigators when designing their clinical trials of nonpharmacological approaches to pain management.
Conclusions
We encourage the increased application of PCTs to produce timely and valuable results and products that will inform the development of safe and effective integrated pain care plans that optimize important patient-centered outcomes.
IMPORTANCE: Some opioids are known immunosuppressants; however, the association of prescribed opioids with clinically relevant immune-related outcomes is understudied, especially among people living ...with HIV. OBJECTIVE: To assess the association of prescribed opioids with community-acquired pneumonia (CAP) by opioid properties and HIV status. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study used data from patients in the Veterans Aging Cohort Study (VACS) from January 1, 2000, through December 31, 2012. Participants in VACS included patients living with and without HIV who received care in Veterans Health Administration (VA) medical centers across the United States. Patients with CAP requiring hospitalization (n = 4246) were matched 1:5 with control individuals without CAP (n = 21 146) by age, sex, race/ethnicity, length of observation, and HIV status. Data were analyzed from March 15, 2017, through August 8, 2018. EXPOSURES: Prescribed opioid exposure during the 12 months before the index date was characterized by a composite variable based on timing (none, past, or current); low (<20 mg), medium (20-50 mg), or high (>50 mg) median morphine equivalent daily dose; and opioid immunosuppressive properties (yes vs unknown or no). MAIN OUTCOME AND MEASURE: CAP requiring hospitalization based on VA and Centers for Medicare & Medicaid data. RESULTS: Among the 25 392 VACS participants (98.9% male; mean SD age, 55 10 years), current medium doses of opioids with unknown or no immunosuppressive properties (adjusted odds ratio AOR, 1.35; 95% CI, 1.13-1.62) and immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and current high doses of opioids with unknown or no immunosuppressive properties (AOR, 2.07; 95% CI, 1.50-2.86) and immunosuppressive properties (AOR, 3.18; 95% CI, 2.44-4.14) were associated with the greatest CAP risk compared with no prescribed opioids or any past prescribed opioid with no immunosuppressive (AOR, 1.24; 95% CI, 1.09-1.40) and immunosuppressive properties (AOR, 1.42; 95% CI, 1.21-1.67), especially with current receipt of immunosuppressive opioids. In stratified analyses, CAP risk was consistently greater among people living with HIV with current prescribed opioids, especially when prescribed immunosuppressive opioids (eg, AORs for current immunosuppressive opioids with medium dose, 1.76 95% CI, 1.20-2.57 vs 2.33 95% CI, 1.60-3.40). CONCLUSIONS AND RELEVANCE: Prescribed opioids, especially higher-dose and immunosuppressive opioids, are associated with increased CAP risk among persons with and without HIV.
Abstract
Objectives
We performed a systematic review and meta-analysis to estimate the effect of early active empirical antibiotics for MRSA on mortality, both in patients admitted with MRSA ...infections and in patients admitted with common infectious syndromes, for whom the causative pathogen may not have been MRSA.
Methods
A systematic literature search was conducted using Embase, MEDLINE, PubMed, Web of Science, Cochrane, Scopus and Google Scholar from the earliest entry through to 26 April 2022. We included studies of patients hospitalized with culture-proven MRSA infections that compared mortality rates depending on whether patients received active empirical antibiotics. The primary outcome was the adjusted OR for mortality with early active empirical antibiotics. After performing random-effects meta-analysis, we estimated the absolute risk reduction in mortality with initial empirical MRSA coverage for common infectious syndromes based on the prevalence of MRSA and baseline mortality rate for each syndrome, as reported in the medical literature.
Results
Of an initial 2136 unique manuscripts, 37 studies (11 661 participants) met our inclusion criteria. Fifteen studies (6066 participants) reported adjusted OR of mortality. The pooled adjusted OR for mortality was 0.64 (95% CI, 0.48–0.84), favouring active empirical antibiotics. The estimated absolute mortality benefit was 0% for patients with pneumonia, 0.1% (95% CI, 0.04–0.2) for non-critically ill patients with soft tissue infections, 0.04% (95% CI, 0.01–0.05) for non-critically ill patients with urinary tract infections, 0.6% (95% CI, 0.2–1.0) for patients with septic shock, and 1.0% (95% CI, 0.3–1.4) for patients with catheter-related infections admitted to ICUs.
Conclusions
For the three most common infections in the hospital, the absolute benefit on mortality of empirical antibiotics against MRSA is 0.1% or less. Meaningful benefit of empirical antimicrobials against MRSA is limited to patients with approximately 30% mortality and 10% prevalence of MRSA. Avoiding empirical antibiotics against MRSA for low-risk infections would substantially reduce the use of anti-MRSA therapy.
Abstract
Objective
The Graded Chronic Pain Scale (GCPS) is frequently used in pain research and treatment to classify mild, bothersome, and high impact chronic pain. This study’s objective was to ...validate the revised version of the GCPS (GCPS-R) in a US Veterans Affairs (VA) healthcare sample to support its use in this high-risk population.
Methods
Data were collected from Veterans (n = 794) via self-report (GCPS-R and relevant health questionnaires) and electronic health record extraction (demographics and opioid prescriptions). Logistic regression, adjusting for age and gender, was used to test for differences in health indicators by pain grade. Adjusted odds ratio (AOR) with 95% confidence intervals (CIs) were reported with CIs not including an AOR of 1 indicating that the difference exceeded chance.
Results
In this population, the prevalence of chronic pain (pain present most or every day, prior 3 months) was 49.3%: 7.1% with mild chronic pain (mild pain intensity and lower interference with activities); 23.3% bothersome chronic pain (moderate to severe pain intensity with lower interference); and 21.1% high impact chronic pain (higher interference). Results of this study mirrored findings in the non-VA validation study; differences between bothersome and high impact were consistent for activity limitations and present but not fully consistent for psychological variables. Those with bothersome chronic pain or high impact chronic pain were more likely to receive long-term opioid therapy compared to those with no/mild chronic pain.
Conclusions
Findings highlight categorical differences captured with the GCPS-R, and convergent validity supports use of the GCPS-R in US Veterans.
Aims
To estimate the influence of non‐medical use of prescription opioids (NMUPO) on heroin initiation among US veterans receiving medical care.
Design
Using a multivariable Cox regression model, we ...analyzed data from a prospective, multi‐site, observational study of HIV‐infected and an age/race/site‐matched control group of HIV‐uninfected veterans in care in the United States. Approximately annual behavioral assessments were conducted and contained self‐reported measures of NMUPO and heroin use.
Setting
Veterans Health Administration (VHA) infectious disease and primary care clinics in Atlanta, Baltimore, New York, Houston, Los Angeles, Pittsburgh and Washington, DC.
Participants
A total of 3396 HIV‐infected and uninfected patients enrolled into the Veterans Aging Cohort Study who reported no life‐time NMUPO or heroin use, had no opioid use disorder diagnoses at baseline and who were followed between 2002 and 2012.
Measurements
The primary outcome measure was self‐reported incident heroin use and the primary exposure of interest was new‐onset NMUPO. Our final model was adjusted for socio‐demographics, pain interference, prior diagnoses of post‐traumatic stress disorder and/or depression and self‐reported other substance use.
Findings
Using a multivariable Cox regression model, we found that non‐medical use of prescription opioids NMUPO was associated positively and independently with heroin initiation adjusted hazard ratio (AHR) = 5.43, 95% confidence interval (CI) = 4.01, 7.35.
Conclusions
New‐onset non‐medical use of prescription opioids (NMUPO) is a strong risk factor for heroin initiation among HIV‐infected and uninfected veterans in the United States who reported no previous history of NMUPO or illicit opioid use.
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