Relationship between HIV viral suppression and multidrug resistant tuberculosis treatment outcomes.

The impact of HIV viral suppression on multidrug resistant tuberculosis (MDR-TB) treatment outcomes among people with HIV (PWH) has not been clearly established. Using secondary data from a cluster-randomized clinical trial among people with MDR-TB in South Africa, we examined the effects of HIV viral suppression at MDR-TB treatment initiation and throughout treatment on MDR-TB outcomes among PWH using multinomial regression. This analysis included 1479 PWH. Viral suppression (457, 30.9%), detectable viral load (524, 35.4%), or unknown viral load (498, 33.7%) at MDR-TB treatment initiation were almost evenly distributed. Having a detectable HIV viral load at MDR-TB treatment initiation significantly increased risk of death compared to those virally suppressed (relative risk ratio [RRR] 2.12, 95% CI 1.11-4.07). Among 673 (45.5%) PWH with a known viral load at MDR-TB outcome, 194 (28.8%) maintained suppression, 267 (39.7%) became suppressed, 94 (14.0%) became detectable, and 118 (17.5%) were never suppressed. Those who became detectable (RRR 11.50, 95% CI 1.98-66.65) or were never suppressed (RRR 9.28, 95% CI 1.53-56.61) were at significantly increased risk of death (RRR 6.37, 95% CI 1.58-25.70), treatment failure (RRR 4.54, 95% CI 1.35-15.24), and loss to follow-up (RRR 7.00, 95% CI 2.83-17.31; RRR 2.97, 95% CI 1.02-8.61) compared to those who maintained viral suppression. Lack of viral suppression at MDR-TB treatment initiation and failure to achieve or maintain viral suppression during MDR-TB treatment drives differences in MDR-TB outcomes. Early intervention to support access and adherence to antiretroviral therapy among PWH should be prioritized to improve MDR-TB treatment outcomes.

Travel distance to rifampicin-resistant tuberculosis treatment and its impact on loss to follow-up: the importance of continued RR-TB treatment decentralization in South Africa.

BACKGROUND: Understanding why patients experience loss to follow-up (LTFU) is essential for TB control. This analysis examines the impact of travel distance to RR-TB treatment on LTFU, which has yet to be analyzed within South Africa. METHODS: We retrospectively analyzed 1436 patients treated for RR-TB at ten South African public hospitals. We linked patients to their residential ward using data reported to NHLS and maps available from the Municipal Demarcation Board. Travel distance was calculated from each patient's ward centroid to their RR-TB treatment site using the georoute command in Stata. The relationship between LTFU and travel distance was modeled using multivariable logistic regression. RESULTS: Among 1436 participants, 75.6% successfully completed treatment and 24.4% were LTFU. The median travel distance was 40.96 km (IQR: 17.12, 63.49). A travel distance > 60 km increased odds of LTFU by 91% (p = 0.001) when adjusting for HIV status, age, sex, education level, employment status, residential locale, treatment regimen, and treatment site. CONCLUSION: People living in KwaZulu-Natal and Eastern Cape travel long distances to receive RR-TB care, placing them at increased risk for LTFU. Policies that bring RR-TB treatment closer to patients, such as further decentralization to PHCs, are necessary to improve RR-TB outcomes.

Successful Multidrug-Resistant Tuberculosis Treatment Without HIV Viral Suppression: A Missed Opportunity.

BACKGROUND: Coinfection with multidrug-resistant tuberculosis (MDR-TB) and HIV is common, but few published studies examine how undergoing MDR-TB treatment affects HIV disease indicators. METHODS: Using data from a nested, retrospective cohort of people with HIV (PWH) and successful MDR-TB treatment outcomes, we built multivariable regression models to explore correlates of HIV viral suppression at MDR-TB treatment completion. RESULTS: Among 531 PWH successfully treated for MDR-TB, mean age was 37.4 years (SD 10.2, interquartile range 30-43), 270 (50.8%) were male, 395 (74.4%) were virally suppressed at MDR-TB outcome, and 259 (48.8%) took bedaquiline. Older age (adjusted odds ratio [aOR] 1.04, 95% confidence interval [CI]: 1.01 to 1.06) increased odds of viral suppression, while having a prior TB episode (aOR 0.45, 95% CI: 0.31 to 0.64), having a detectable viral load at MDR-TB treatment initiation (aOR 0.17, 95% CI: 0.09 to 0.30), living in a township (aOR 0.49, 95% CI: 0.28 to 0.87), and being changed from efavirenz-based antiretroviral therapy (ART) to a protease inhibitor due to bedaquiline usage (aOR 0.19, 95% CI: 0.04 to 0.82) or not having an ART change while on bedaquiline (aOR 0.29, 95% CI: 0.11 to 0.75) lowered odds of viral suppression. Changing from efavirenz to nevirapine due to bedaquiline usage did not significantly affect odds of viral suppression (aOR 0.41, 95% CI: 0.16 to 1.04). CONCLUSIONS: Increased pill burden and adverse treatment effects did not significantly affect HIV viral suppression while switching ART to a protease inhibitor to accommodate bedaquiline or not changing ART while taking bedaquiline did, suggesting that PWH and MDR-TB may benefit from additional support if they must switch ART.

Polypharmacy, Potentially Inappropriate Medications, and Drug-Drug Interactions in Vulnerable Older Adults With Advanced Cancer Initiating Cancer Treatment.

PURPOSE: Polypharmacy is prevalent in older adults starting cancer treatment and associated with potentially inappropriate medications (PIM), potential drug-drug interactions (DDI), and drug-cancer treatment interactions (DCI). For a large cohort of vulnerable older adults with advanced cancer starting treatment, we describe patterns of prescription and nonprescription medication usage, the prevalence of PIM, and the prevalence, severity, and type of DDI/DCI. METHODS: This secondary analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment (University of Rochester Cancer Center [URCC] 13059; PI: Mohile). PIM were categorized using 2019 Beers criteria and Screening Tool of Older Persons' Prescriptions. Potential DDI/DCI were evaluated using Lexi-Interact Online. Medication classification followed the World Health Organization Anatomical Therapeutic Chemical system. Bivariate associations were evaluated between sociodemographic and geriatric assessment (GA) measures and medication measures. Chord diagrams and network analysis were used to understand and describe DDI/DCI. RESULTS: Among 718 patients (mean age 77.6 years), polypharmacy (≥5 medications), excessive polypharmacy (≥10 medications), and ≥1 PIM were identified in 61.3%,14.5%, and 67.1%, respectively. Cardiovascular medications were the most prevalent (47%), and nonprescription medications accounted for 26% of total medications and 40% of PIM. One-quarter of patients had ≥1 potential major DDI not involving cancer treatment, and 5.4% had ≥1 potential major DCI. Each additional medication increased the odds of a potential major DDI and DCI by 39% and 12%, respectively. Polypharmacy and PIM are associated with multiple GA domains. CONCLUSION: In a cohort of vulnerable older adults with advanced cancer starting treatment, polypharmacy, PIM, and potential DDI/DCI are very common. Nonprescription medications are frequently PIMs and/or involved in potential DDI/DCI.

Association of Oncologist-Patient Communication With Functional Status and Physical Performance in Older Adults: A Secondary Analysis of a Cluster Randomized Clinical Trial.

Importance: The functional status and physical performance of older adults with cancer are underassessed and undertreated despite the high prevalence of impaired functional status and physical performance in this population and their associations with chemotherapy-induced toxic effects and mortality. Objective: To examine the association between providing oncologists with a geriatric assessment (GA) summary with recommendations and having oncologist-patient conversations about functional and physical performance. Design, Setting, and Participants: Data for this secondary analysis were collected from October 29, 2014, to April 28, 2017, for a national cluster randomized clinical trial conducted by the University of Rochester Cancer Center National Cancer Institute Community Oncology Research Program evaluating the effect of a GA intervention on patient satisfaction with communication about aging-related concerns. There were 17 practice clusters in the intervention group and 14 in the usual care group. All 541 participants underwent a GA including standardized functional and physical performance measures and had 1 clinical encounter audio-recorded, transcribed, and blindly coded to categorize conversations by GA domain. Participants were aged 70 years or older, with a stage III or IV solid tumor or lymphoma with palliative treatment intent, and impairment in 1 or more GA domain. Statistical analysis was performed from August 18, 2020, to January 10, 2022. Interventions: Oncologist practices randomized to the intervention received a GA summary and validated recommendations for each patient prior to the audio-recorded clinical encounter. Main Outcomes and Measures: The primary analysis of this clinical trial assessed the effect of the intervention on patient satisfaction with oncologist communication about aging-related concerns. This secondary analysis assessed the post hoc hypothesis that the intervention would be associated with an increase in the proportion of patients having conversations with their oncologists and receiving oncologist recommendations specific to functional and physical performance concerns. Results: A total of 541 patients (276 men [51%]; mean [SD] age, 77.5 [5.2] years [range, 70-96 years]) were analyzed at baseline. Excluding 13 patients without audio recordings, 86% of patients (95% CI, 78%-91%) in the intervention group vs 59% of patients (95% CI, 47%-69%; P < .001) receiving usual care had conversations about functional or physical performance. Conversations were more frequently initiated by oncologists in the intervention group (84%; 95% CI, 77%-90%) than oncologists in the usual care group (58%; 95% CI, 45%-70%; P < .001). Oncologists in the intervention group were more likely to address patients' concerns (43%; 95% CI, 33%-53%) than oncologists in the usual care group (17%; 95% CI, 10%-26%; P < .001). Conclusions and Relevance: In this secondary analysis of a cluster randomized clinical trial, providing oncologists with a GA summary was associated with an increase in the number of oncologist-patient conversations about functional and physical performance-related concerns with recommendations to address these concerns. These findings support the use of the GA summary and recommendations as important tools in caring for older adults with advanced cancer and functional or physical impairments. Trial Registration: ClinicalTrials.gov Identifier: NCT02107443.

Evaluating the association of frailty with communication about aging-related concerns between older patients with advanced cancer and their oncologists.

BACKGROUND: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. METHODS: This was a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and impairment on 1 or more GA domains (ClinicalTrials.gov Identifier NCT02107443; principal investigator Supriya G. Mohile). Practice sites were randomized to either the GA-intervention or usual care. Frailty was assessed with a deficit accumulation index (range, 0-1), and patients were stratified as robust (0 to <0.2), prefrail (0.2 to <0.35), or frail (≥0.35). The clinic visit after the GA-intervention was audio-recorded, transcribed, and coded to evaluate the number and quality of conversations about aging-related concerns. Linear mixed models examined differences in the number and quality of conversations within and between arms. All P values were 2-sided. RESULTS: Patients (n = 541) were classified as robust (27%), prefrail (42%), or frail (31%). In the usual care arm, frail patients (vs robust ones) engaged in more aging-related conversations (adjusted mean difference, 1.73; 95% confidence interval [CI], 0.59-2.87), conversations of higher quality (difference, 1.12; 95% CI, 0.24-2.0), and more discussions about evidence-based recommendations (difference, 0.71; 95% CI, 0.04-1.38; all P values ≤ .01). Similarly, in the GA intervention arm, frail patients (vs robust ones) engaged in more aging-related conversations (difference, 2.49; 95% CI, 1.51-3.47), conversations of higher quality (difference, 1.31; 95% CI, 0.56-2.06), and more discussions about evidence-based recommendations (difference, 0.87; 95% CI, 0.32-1.42; all P values ≤ .01). Furthermore, the GA-intervention significantly improved the number and quality of conversations in all patients: robust, prefrail, and frail (all P values ≤ .01). CONCLUSIONS: Patients with higher degrees of frailty and those exposed to the GA-intervention had more and higher quality conversations about aging-related concerns with oncologists. LAY SUMMARY: A geriatric assessment (GA) intervention improves communication about aging-related concerns, but its effect on communication in patients with various levels of frailty is unknown. This study conducted a secondary analysis of a nationwide trial of patients aged ≥70 years with incurable cancer and 1 or more GA domain impairments. Patients were stratified as robust, prefrail, or frail. The number and quality of conversations about aging-related concerns that occurred during the clinic visit after the GA-intervention were determined. Patients with higher degrees of frailty and those in the GA intervention arm had more and higher quality conversations about aging-related concerns with oncologists.

Evaluation of geriatric assessment and management on the toxic effects of cancer treatment (GAP70+): a cluster-randomised study.

BACKGROUND: Older adults with advanced cancer are at a high risk for treatment toxic effects. Geriatric assessment evaluates ageing-related domains and guides management. We examined whether a geriatric assessment intervention can reduce serious toxic effects in older patients with advanced cancer who are receiving high risk treatment (eg, chemotherapy). METHODS: In this cluster-randomised trial, we enrolled patients aged 70 years and older with incurable solid tumours or lymphoma and at least one impaired geriatric assessment domain who were starting a new treatment regimen. 40 community oncology practice clusters across the USA were randomly assigned (1:1) to the intervention (oncologists received a tailored geriatric assessment summary and management recommendations) or usual care (no geriatric assessment summary or management recommendations were provided to oncologists) by means of a computer-generated randomisation table. The primary outcome was the proportion of patients who had any grade 3-5 toxic effect (based on National Cancer Institute Common Terminology Criteria for Adverse Events version 4) over 3 months. Practice staff prospectively captured toxic effects. Masked oncology clinicians reviewed medical records to verify. The study was registered with ClinicalTrials.gov, NCT02054741. FINDINGS: Between July 29, 2014, and March 13, 2019, we enrolled 718 patients. Patients had a mean age of 77·2 years (SD 5·4) and 311 (43%) of 718 participants were female. The mean number of geriatric assessment domain impairments was 4·5 (SD 1·6) and was not significantly different between the study groups. More patients in intervention group compared with the usual care group were Black versus other races (40 [11%] of 349 patients vs 12 [3%] of 369 patients; p<0·0001) and had previous chemotherapy (104 [30%] of 349 patients vs 81 [22%] of 369 patients; p=0·016). A lower proportion of patients in the intervention group had grade 3-5 toxic effects (177 [51%] of 349 patients) compared with the usual care group (263 [71%] of 369 patients; relative risk [RR] 0·74 (95% CI 0·64-0·86; p=0·0001). Patients in the intervention group had fewer falls over 3 months (35 [12%] of 298 patients vs 68 [21%] of 329 patients; adjusted RR 0·58, 95% CI 0·40-0·84; p=0·0035) and had more medications discontinued (mean adjusted difference 0·14, 95% CI 0·03-0·25; p=0·015). INTERPRETATION: A geriatric assessment intervention for older patients with advanced cancer reduced serious toxic effects from cancer treatment. Geriatric assessment with management should be integrated into the clinical care of older patients with advanced cancer and ageing-related conditions. FUNDING: National Cancer Institute.

Prevalence of and factors associated with treatment modification at first cycle in older adults with advanced cancer receiving palliative treatment.

INTRODUCTION: Treatment toxicities are common in older adults with cancer and consequently, treatment modifications are sometimes considered. We evaluated the prevalence and factors associated with treatment modifications at the first cycle in older patients receiving palliative systemic treatment. METHODS: Patients (n = 369) from the GAP 70+ Trial (NCT02054741; PI: Mohile) usual care arm were included. Enrolled patients were aged 70+ with advanced cancer and ≥ 1 Geriatric Assessment (GA) domain impairment. Treatment modification was defined as any change from National Comprehensive Cancer Network guidelines or published clinical trials. Baseline variables included: 1) sociodemographic factors; 2) clinical variables; 3) GA domains; and 4) physician beliefs about life expectancy. Bivariate analyses and multivariable cluster-weighted generalized estimating equation model were conducted to assess the association of baseline variables with cycle 1 treatment modifications. RESULTS: Mean age was 77.2 years (range: 70-94); 62% had lung or gastrointestinal cancers, and 35% had treatment modifications at cycle 1. Increasing age by one year (odds ratio (OR) 1.1, 95% confidence interval [CI] 1.0-1.2), receipt of ≥second line of chemotherapy (OR 1.8, CI 1.1-3.0), functional impairment (OR 1.6, CI 1.1-2.3) and income ≤$50,000 (OR 1.7, CI 1.1-2.4) were independently associated with a higher likelihood of cycle 1 treatment modification. CONCLUSION: Treatment modifications occurred in 35% of older adults with advanced cancer at cycle 1. Increasing age, receipt of ≥second line of chemotherapy, functional impairment, and lower income were independently associated with treatment modifications. These findings emphasize the need for evidence-based regimens in older adults with cancer and GA impairments.

Association of Polypharmacy and Potentially Inappropriate Medications With Physical Functional Impairments in Older Adults With Cancer.

BACKGROUND: Polypharmacy and potentially inappropriate medications (PIMs) are prevalent in older adults with cancer, but their associations with physical function are not often studied. This study examined the associations of polypharmacy and PIMs with physical function in older adults with cancer, and determined the optimal cutoff value for the number of medications most strongly associated with physical functional impairment. METHODS: This cross-sectional analysis used baseline data from a randomized study enrolling patients aged ≥70 years with advanced cancer starting a new systemic cancer treatment. We categorized PIM using 2015 American Geriatrics Society Beers Criteria. Three validated physical function measures were used to assess patient-reported impairments: activities of daily living (ADL) scale, instrumental activities of daily living (IADL) scale, and the Older Americans Resources and Services Physical Health (OARS PH) survey. Optimal cutoff value for number of medications was determined by the Youden index. Separate multivariate logistic regressions were then performed to examine associations of polypharmacy and PIMs with physical function measures. RESULTS: Among 439 patients (mean age, 76.9 years), the Youden index identified ≥8 medications as the optimal cutoff value for polypharmacy; 43% were taking ≥8 medications and 62% were taking ≥1 PIMs. On multivariate analysis, taking ≥8 medications was associated with impairment in ADL (adjusted odds ratio [aOR], 1.64; 95% CI, 1.01-2.58) and OARS PH (aOR, 1.73; 95% CI, 1.01-2.98). PIMs were associated with impairments in IADL (aOR, 1.72; 95% CI, 1.09-2.73) and OARS PH (aOR, 1.97; 95% CI, 1.15-3.37). A cutoff of 5 medications was not associated with any of the physical function measures. CONCLUSIONS: Physical function, an important component of outcomes for older adults with cancer, is cross-sectionally associated with polypharmacy (defined as ≥8 medications) and with PIMs. Future studies should evaluate the association of polypharmacy with functional outcomes in this population in a longitudinal fashion.