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Parkinson disease (PD) is the second most common age-related neurodegenerative condition diagnosed in North America. We recently demonstrated, using multiple epidemiological data sources, that the prevalence of PD diagnoses was greater than previously reported and currently used for clinical, research, and policy decision-making. Prior PD incidence estimates have varied, for unclear reasons. There is a need for improved estimates of PD incidence, not only for care delivery planning and future policy but also for increasing our understanding of disease risk. The objective of this study was thus to investigate the incidence of Parkinson disease across five epidemiological cohorts in North America in a common year, 2012. The cohorts contained data on 6.7 million person-years of adults ages 45 and older, and 9.3 million person-years of adults ages 65 and older. Our estimates of age-sex-adjusted incidence of PD ranged from 108 to 212 per 100,000 among persons ages 65 and older, and from 47 to 77 per 100,00 among persons ages 45 and older. PD incidence increased with age and was higher among males. We also found persistent spatial clustering of incident PD diagnoses in the U.S. PD incidence estimates varied across our data sources, in part due to case ascertainment and diagnosis methods, but also possibly due to the influence of population factors (prevalence of genetic risk factors or protective markers) and geographic location (exposure to environmental toxins). Understanding the source of these variations will be important for health care policy, research, and care planning.

Estimates of the prevalence of Parkinson's disease in North America have varied widely and many estimates are based on small numbers of cases and from small regional subpopulations. We sought to estimate the prevalence of Parkinson's disease in North America by combining data from a multi-study sampling strategy in diverse geographic regions and/or data sources. Five separate cohort studies in California (2), Minnesota (1), Hawaii USA (1), and Ontario, Canada (1) estimated the prevalence of PD from health-care records (3), active ascertainment through facilities, large group, and neurology practices (1), and longitudinal follow-up of a population cohort (1). US Medicare program data provided complementary estimates for the corresponding regions. Using our age- and sex-specific meta-estimates from California, Minnesota, and Ontario and the US population structure from 2010, we estimate the overall prevalence of PD among those aged ≥45 years to be 572 per 100,000 (95% confidence interval 537-614) that there were 680,000 individuals in the US aged ≥45 years with PD in 2010 and that that number will rise to approximately 930,000 in 2020 and 1,238,000 in 2030 based on the US Census Bureau population projections. Regional variations in prevalence were also observed in both the project results and the Medicare-based calculations with which they were compared. The estimates generated by the Hawaiian study were lower across age categories. These estimates can guide health-care planning but should be considered minimum estimates. Some heterogeneity exists that remains to be understood.

BACKGROUND: To explore effects of a health risk appraisal for older people (HRA-O) program with reinforcement, we conducted a randomized controlled trial in 21 general practices in Hamburg, Germany. METHODS: Overall, 2,580 older patients of 14 general practitioners trained in reinforcing recommendations related to HRA-O-identified risk factors were randomized into intervention (n = 878) and control (n = 1,702) groups. Patients (n = 746) of seven additional matched general practitioners who did not receive this training served as a comparison group. Patients allocated to the intervention group, and their general practitioners, received computer-tailored written recommendations, and patients were offered the choice between interdisciplinary group sessions (geriatrician, physiotherapist, social worker, and nutritionist) and home visits (nurse). RESULTS: Among the intervention group, 580 (66%) persons made use of personal reinforcement (group sessions: 503 [87%], home visits: 77 [13%]). At 1-year follow-up, persons in the intervention group had higher use of preventive services (eg, influenza vaccinations, adjusted odds ratio 1.7; 95% confidence interval 1.4-2.1) and more favorable health behavior (eg, high fruit/fiber intake, odds ratio 2.0; 95% confidence interval 1.6-2.6), as compared with controls. Comparisons between intervention and comparison group data revealed similar effects, suggesting that physician training alone had no effect. Subgroup analyses indicated favorable effects for HRA-O with personal reinforcement, but not for HRA-O without reinforcement. CONCLUSIONS: HRA-O combined with physician training and personal reinforcement had favorable effects on preventive care use and health behavior. [ABSTRACT FROM AUTHOR]

BACKGROUND AND AIMS: In clinical practice, the status of living alone is often used as the only measure describing an older person's social network. We evaluated whether additional use of a brief social network measure provides relevant additional information in relation to social support and engagement. METHODS: Cross-sectional survey of 6982 community- dwelling adults 65 years or older living in London, UK; Hamburg, Germany; and Solothurn, Switzerland. Data were collected using the self-administered multidimensional Health Risk Appraisal Questionnaire. Multivariate models were used to analyse adjusted correlations between the two measures of social network (living alone status, risk for social isolation with marginal family and friend network subscales) and potential consequences of inadequate social network (marginal emotional or instrumental support, lack of social engagement). RESULTS: Living alone status was more strongly associated with marginal instrumental support [OR=7.6 (95% CI 6.3, 9.1)] than with marginal emotional support [OR=4.2 (95% CI 3.4, 5.1)], and showed no statistically significant association with lack of social engagement [OR=0.9 (95% CI 0.8, 1.0)]. Risk of social isolation was more strongly related to marginal emotional support [OR=6.6 (95% CI 5.4, 8.0)] than to marginal instrumental support [OR=3.3 (95% CI 2.8, 4.0)], and was moderately related to lack of social engagement [OR=2.9 (95% CI 2.5, 3.4]. Marginal family and friend network subscales showed consistent and unique associations with social support and social engagement. CONCLUSION: Findings suggest that living alone status and a brief measure of social network identifies distinctive at-risk groups and potential pathways for intervention. Geriatric assessment programs including both social network measures may provide useful information about potentially modifiable social network risks in older persons. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the influence of neurally adjusted ventilatory assist (NAVA) and positive end-expiratory pressure (PEEP) on the control of breathing in rabbits with acute lung injury. DESIGN: Prospective animal study. SETTING: Experimental laboratory in a university hospital. SUBJECTS: Male White New Zealand rabbits (n = 18). INTERVENTION: Spontaneously breathing rabbits with hydrochloric acid-induced lung injury were ventilated with NAVA and underwent changes in NAVA gain and PEEP (six nonvagotomized and five vagotomized). Seven other nonvagotomized rabbits underwent 4 hrs of ventilation with hourly titration of PEEP, Fio2, and NAVA gain. MEASUREMENTS AND MAIN RESULTS: We studied diaphragm electrical activity, respiratory pressures, and breathing pattern. After lung injury, 0 cm H2O of PEEP resulted in high tonic and no discernible phasic diaphragm electrical activity in the nonvagotomized rabbits; stepwise increases in PEEP (up to 11.7 +/- 2.6 cm H2O) reduced tonic but increased phasic diaphragm electrical activity. Increasing the NAVA gain reduced phasic diaphragm electrical activity to almost half and abolished esophageal pressure swings. Tidal volume remained at 4-5 mL/kg, and respiratory rate did not change. In the vagotomized group, lung injury did not induce tonic activity, and phasic activity and tidal volume were several times higher than in the nonvagotomized rabbits. Four hours of breathing with NAVA restored breathing pattern and neural and mechanical breathing efforts to pre-lung injury levels. CONCLUSIONS: Acute lung injury can cause a vagally mediated atypical diaphragm activation pattern in spontaneously breathing rabbits. Modulation of PEEP facilitates development of phasic diaphragm electrical activity, whereupon implementation of NAVA can efficiently maintain unloading of the respiratory muscles without delivering excessive tidal volume in rabbits with intact vagal function. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To validate the Probability of Repeated Admission (Pra) questionnaire, a widely used self-administered tool for predicting future healthcare use in older persons, in three European healthcare systems. DESIGN: Prospective study with 1-year follow-up. SETTING: Hamburg, Germany; London, United Kingdom; Canton of Solothurn, Switzerland. PARTICIPANTS: Nine thousand seven hundred thirteen independently living community-dwelling people aged 65 and older. MEASUREMENTS: Self-administered eight-item Pra questionnaire at baseline. Self-reported number of hospital admissions and physician visits during 1 year of follow-up. RESULTS: In the combined sample, areas under the receiver operating characteristic curves (AUCs) were 0.64 (95% confidence interval (CI)=0.62-0.66) for the prediction of one or more hospital admissions and 0.68 (95% CI=0.66-0.69) for the prediction of more than six physician visits during the following year. AUCs were similar between sites. In comparison, prediction models based on a person's age and sex alone exhibited poor predictive validity (AUC or= 0.5) were 2.3 times as likely (95% CI=2.1-2.6) as low-risk individuals to have a hospital admission, and 2.1 times as likely (95% CI=2.0-2.2) to have more than six physician visits. CONCLUSION: The Pra instrument exhibits good validity for predicting future health service use on a population level in different healthcare settings. Administrative data have shown similar predictive validity, but in practice, such data are often not available. The Pra is likely of high interest to governments and health insurance companies worldwide as a basis for programs aimed at health risk management in older persons. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine (1) the extent of agreement between the CAGE (acronym for cut down, annoyed by criticism, guilty about drinking, eye-opener drinks) and the Short Michigan Alcoholism Screening Test-Geriatric Version (SMAST-G) in identifying older persons who may have possible alcohol use disorders (AUDs) and (2) whether persons identified as having possible AUDs by each of these screening measures differ in their drinking, demographic, or health-related characteristics. DESIGN: Secondary analysis of a cross-sectional study using data from a self-administered mailed survey sample. SETTING: Three organizations were surveyed: (1) members of the American Association of Retired Persons and, in southern California, (2) managed care enrollees in a large medical group and (3) attendees of a community-based senior health center. PARTICIPANTS: One thousand eight hundred eighty-nine persons aged 55 and older completing a health risk appraisal for older persons (Health Risk Appraisal for the Elderly (HRA-E)). MEASUREMENTS: The HRA-E included items on drinking behaviors (including amount of alcohol use, the CAGE, and the SMAST-G) and health and demographic characteristics. RESULTS: Twenty-six percent of all persons screened positive on the CAGE or the SMAST-G. Fewer than half of all persons screening positive on either the CAGE or the SMAST-G, screened positive on both measures. Among current drinkers, persons screening positive on the SMAST-G alone drank less than persons screening positive on the CAGE alone, and these persons drank less than those screening positive on both the SMAST-G and the CAGE. More men screened positive on the CAGE alone than on the SMAST-G alone. CONCLUSION: Fewer than half of persons screening positive on either the CAGE or the SMAST-G screened positive on both measures, suggesting that these instruments may be capturing different aspects of unsafe drinking. A screening strategy employing both brief measures may identify more AUDs among older persons having differing demographic and health characteristics. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study explored differences between refusers and participants in a longitudinal study with extensive baseline and follow-up information. METHODS: Results of a trial comparing 791 participants and 401 community-residing older adults who refused to participate in a study concerning preventive home visits were examined. Information was collected from interviews, insurance records, and government files. RESULTS: Despite similarities in terms of age, sex, and self-perceived health at baseline, 3-year follow-up data indicated that refusers had a 1.58-fold higher risk of entering a nursing home than participants. There were additional differences between refusers and participants when refusers were categorized in 4 subgroups based on self-reported reason for refusal (too ill, too healthy, no interest, and other reasons). CONCLUSIONS: Future studies should include follow-up data to allow comparisons between refusers and participants and should address the presence of multiple subgroups of refusers. [ABSTRACT FROM AUTHOR]

Functional assessment promotes continued independence and quality of life, even for the very old. These tips will help you evaluate older patients despite the obstacles of limited time and meager reimbursement. [ABSTRACT FROM AUTHOR]

Objective: To quantify the appropriateness of medication prescriptions in nursing home residents.Design: Prospective, cohort study.Setting: Twelve nursing homes in the greater Los Angeles area.Participants: A total of 1106 nursing home residents.Main Outcome Measures: The appropriateness of medication prescriptions was evaluated using explicit criteria developed through consensus by 13 experts from the United States and Canada. These experts identified 19 drugs that should generally be avoided and 11 doses, frequencies, or durations of use of specific drugs that generally should not be exceeded.Results: Based on the consensus criteria, 40% of residents received at least one inappropriate medication order, and 10% received two or more inappropriate medication orders concurrently; 7% of all prescriptions were inappropriate. Physicians prescribed a greater number of inappropriate medications for female residents. Regression analysis, corrected for clustering effects within facilities, showed that a greater number of inappropriate medication prescriptions were ordered in larger nursing homes. Inappropriate prescriptions were not related to the proportion of Medicaid (Medi-Cal) residents or the number of physicians practicing in the homes.Conclusions: Inappropriate medication prescribing in nursing homes is common. Female residents and residents of large nursing homes are at the greatest risk for receiving an inappropriate prescription. [ABSTRACT FROM AUTHOR]

To assess the adequacy of training in public health and aging, all accredited schools of public health, as well as other departments offering a Masters in Public Health degree, were surveyed. Results suggest that the current scope and quantity of training in public health and aging is inadequate, except for in a few schools of public health. Barriers and facilitators, such as finances, were similar for all institutions. The lack of appropriately trained faculty was a problem, particularly for institutions with no health and aging courses. A relatively small number of public health graduate students take courses in health and aging. In contrast, there are thousands of public, nonprofit, and private agencies that could use public health professionals with such education. It is concluded that the modest scope of health and aging course work and the small number of students in those courses does not come close to meeting the need for knowledgeable public health and aging practitioners. [ABSTRACT FROM AUTHOR]

To lay the groundwork for devising, improving and implementing strategies to prevent or delay the onset of disability in the elderly, we conducted a systematic literature review of longitudinal studies published between 1985 and 1997 that reported statistical associations between individual base-line risk factors and subsequent functional status in community-living older persons. Functional status decline was defined as disability or physical function limitation. We used MEDLINE, PSYCINFO, SOCA, EMBASE, bibliographies and expert consultation to select the articles, 78 of which met the selection criteria. Risk factors were categorized into 14 domains and coded by two independent abstractors. Based on the methodological quality of the statistical analyses between risk factors and functional outcomes (e.g. control for base-line functional status, control for confounding, attrition rate), the strength of evidence was derived for each risk factor. The association of functional decline with medical findings was also analyzed. The highest strength of evidence for an increased risk in functional status decline was found for (alphabetical order) cognitive impairment, depression, disease burden (comorbidity), increased and decreased body mass index, lower extremity functional limitation, low frequency of social contacts, low level of physical activity, no alcohol use compared to moderate use, poor self-perceived health, smoking and vision impairment. The review revealed that some risk factors (e.g. nutrition, physical environment) have been neglected in past research. This review will help investigators set priorities for future research of the Disablement Process, plan health and social services for elderly persons and develop more cost-effective programs for preventing disability among them. [ABSTRACT FROM AUTHOR]

Genetic testing for Parkinson's disease (PD) is infrequently performed due to perceptions of low utility. We investigated the personal utility in PD GENEration and how results lead to enrollment in additional research studies. Participants (n = 972) underwent genetic testing, results disclosure, genetic counseling, and completed a survey examining the perceived personal utility of their results and interest in participating in additional studies. Most participants found their genetic test results useful, including satisfying curiosity (81%), feeling good about helping the medical community (80%), and having information to share with family (77%). There were no significant differences in responses based on result type. Forty-five percent of participants expressed interest in participating in research studies; whereas 16% of participants confirmed enrollment. Our results suggest that participants find personal utility in genetic testing regardless of results. Although participants may be interested in enrolling in additional research, they may need support and resources., (© 2024. The Author(s).)

Background: Depression is common in Parkinson's disease (PD) but is underrecognized clinically. Although systematic screening is a recommended strategy to improve depression recognition in primary care practice, it has not been widely used in PD care., Methods: The 15-item Geriatric Depression Scale (GDS-15) was implemented at 5 movement disorders clinics to screen PD patients. Sites developed processes suited to their clinical workflow. Qualitative interviews with clinicians and patients provided information on feasibility, acceptability, and perceived utility., Results: Prior to implementation, depression screening was recorded in 12% using a formal instrument; 64% were screened informally by clinical interview, and no screening was recorded in 24%. Of 1406 patients seen for follow-up care during the implementation period, 88% were screened, 59% using the GDS-15 (self-administered in 51% and interviewer administered in 8%), a nearly 5-fold increase in formal screening. Lack of clinician or staff time and inability to provide the GDS-15 to the patient ahead of the visit were the most commonly cited reasons for lack of screening using the GDS-15; 378 (45%) patients completing the GDS-15 screened positive for depression, and 137 were enrolled for a 12-month prospective follow-up. Mean GDS-15 scores improved from 8.8 to 7.0 (P < 0.0001) and the 39-item Parkinson's Disease Questionnaire emotional subscore from 42.2 to 36.7 (P = 0.0007)., Conclusions: Depression screening in PD using a formal instrument can be achieved at much higher levels than is currently practiced, but there are barriers to implementing this in clinical practice. An individual site-specific process is necessary to optimize screening rates., (© 2024 The Author(s). Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Variants in seven genes (LRRK2, GBA1, PRKN, SNCA, PINK1, PARK7 and VPS35) have been formally adjudicated as causal contributors to Parkinson's disease; however, individuals with Parkinson's disease are often unaware of their genetic status since clinical testing is infrequently offered. As a result, genetic information is not incorporated into clinical care, and variant-targeted precision medicine trials struggle to enrol people with Parkinson's disease. Understanding the yield of genetic testing using an established gene panel in a large, geographically diverse North American population would help patients, clinicians, clinical researchers, laboratories and insurers better understand the importance of genetics in approaching Parkinson's disease. PD GENEration is an ongoing multi-centre, observational study (NCT04057794, NCT04994015) offering genetic testing with results disclosure and genetic counselling to those in the US (including Puerto Rico), Canada and the Dominican Republic, through local clinical sites or remotely through self-enrolment. DNA samples are analysed by next-generation sequencing including deletion/duplication analysis (Fulgent Genetics) with targeted testing of seven major Parkinson's disease-related genes. Variants classified as pathogenic/likely pathogenic/risk variants are disclosed to all tested participants by either neurologists or genetic counsellors. Demographic and clinical features are collected at baseline visits. Between September 2019 and June 2023, the study enrolled 10 510 participants across >85 centres, with 8301 having received results. Participants were: 59% male; 86% White, 2% Asian, 4% Black/African American, 9% Hispanic/Latino; mean age 67.4 ± 10.8 years. Reportable genetic variants were observed in 13% of all participants, including 18% of participants with one or more 'high risk factors' for a genetic aetiology: early onset (<50 years), high-risk ancestry (Ashkenazi Jewish/Basque/North African Berber), an affected first-degree relative; and, importantly, in 9.1% of people with none of these risk factors. Reportable variants in GBA1 were identified in 7.7% of all participants; 2.4% in LRRK2; 2.1% in PRKN; 0.1% in SNCA; and 0.2% in PINK1, PARK7 or VPS35 combined. Variants in more than one of the seven genes were identified in 0.4% of participants. Approximately 13% of study participants had a reportable genetic variant, with a 9% yield in people with no high-risk factors. This supports the promotion of universal access to genetic testing for Parkinson's disease, as well as therapeutic trials for GBA1 and LRRK2-related Parkinson's disease., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Before a medical procedure requiring anesthesia, patients are required to not eat or drink non-clear fluids for 6 h and not drink clear fluids for 2 h. Fasting durations in standard practice far exceed these minimum thresholds due to uncertainties in procedure start time. The aim of this retrospective, observational study was to compare fasting durations arising from standard practice with different approaches for calculating the timepoint at which patients are instructed to stop eating and drinking. Scheduling data for procedures performed in the cardiac catheterization laboratory of an academic hospital in Canada (January 2020 to April 2022) were used. Four approaches utilizing machine learning (ML) and simulation were used to predict procedure start times and calculate when patients should be instructed to start fasting. Median fasting duration for standard practice was 10.08 h (IQR 3.5) for both food and clear fluids intake. The best performing alternative approach, using tree-based ML models to predict procedure start time, reduced median fasting from food/non-clear fluids to 7.7 h (IQR 2) and clear liquids fasting to 3.7 h (IQR 2.4). 97.3% met the minimum fasting duration requirements (95% CI 96.9% to 97.6%). Further studies are required to determine the effectiveness of operationalizing this approach as an automated fasting alert system., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: To evaluate the feasibility and impact of offering genetic testing and counseling to patients with Parkinson's disease (PD), with the potential to enroll in gene-targeted clinical trials and improve clinical care., Methods: A multicenter, exploratory pilot study at 7 academic hospital sites in the United States tracked enrollment and randomized participants to receive results and genetic counseling at local sites or by genetic counselors, remotely. Follow-up surveys measured participant/provider satisfaction, knowledge, and psychological impact., Results: From September 5, 2019 to January 4, 2021, 620 participants were enrolled and 387 completed outcome surveys. There were no significant differences in outcomes between local and remote sites, with both arms reporting high knowledge and satisfaction scores (>80%). Notably, 16% of those tested had reportable PD gene variants (pathogenic/likely pathogenic/risk allele)., Conclusion: Local clinicians, as well as genetic counselors, with educational support as needed, can effectively return genetic results for PD as we observed favorable outcome measures in both groups. Increasing access to PD genetic testing and counseling is urgent; this can inform future efforts to integrate genetic testing and counseling into clinical care for all those with PD., Competing Interests: Conflict of Interest Lola Cook received partial funding of salaries from the Michael J. Fox Foundation (MJFF) and Parkinson’s Foundation; Jennifer Verbrugge received partial funding of salaries from the Michael J. Fox Foundation (MJFF) and Parkinson’s Foundation and received travel funding for Movement Disorders Society International Congress, Madrid, Spain September 2022, abstract and poster presentation PD GENEration Clinical Phase: Genetic Diagnostic Yield and Clinical Characteristics by the Parkinson’s Foundation and paid to Indiana University School of Medicine; Tae-Hwi Schwantes-An, no disclosures; Jeanine Schulze received partial funding of salaries from the MJFF and Parkinson’s Foundation; James C. Beck is employed by the Parkinson’s Foundation, and receives funding for grants through their institution from NIH; Anna Naito is employed by the Parkinson’s Foundation; Anne Hall is a research advocate and received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member; Amanda K. Chan, no disclosures; Cynthia J. Casaceli, no disclosures; Karen Marder received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, receives funding of grants from NIH, MJ FOX, CHDI, HSG, HDSA, Prilenia, Novartis, Roche, Springer, receives consulting fees from Novartis, and receives funding for leadership on Enroll HD Oversight Committee (CHDI) and HSG steering committee; Martha Nance received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, received payment for presentation at Parkinson’s Foundation and Parkinson Study Group conferences, received support for attending Parkinson Study Group conference, and is the Chair of Genetics and Environment Working Group for Parkinson Study Group; Michael A. Schwarzschild received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, receives funding of grants or conference support from NIH, MJFF, Farmer Family Foundation, Sergey Brin Family Foundation, American Parkinson’s Disease Association, Cure Parkinson’s, Parkinson’s Foundation, Harvard School of Public Health (NIH, DoD), GSK, GE Healthcare, receives consulting fees through Parkinson Study Group for PSG advisory services (including to Bial, Biogen [LUMA/LIGHTHOUSE trials global SC], UCB [ORHCESTRA trial PSG SC]) and through Sutter Health (NIA), Northwestern Univ (NINDS), Cure Parkinson’s for Steering Committee services (for TOPAZ and SPARX3), International Linked Clinical Trial Committee (CP), participates on an Alzheimer’s drug trial Data Monitoring Committee services for Eli Lilly & Co., and is Chair, Exec. Committee for Parkinson Study Group; Tanya Simuni received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, receives funding of manuscript by MJFF for Parkinson’s Research, receives funding of grants by Amneal, Biogen, Roche, Neuroderm, Sanofi, Prevail and UCB, is an investigator for NINDS, MJFF, Parkinson’s Foundation studies, receives consulting fees from 4D Pharma, Acadia, AcureX, AskBio, Amneal, Blue Rock Therapeutics, Caraway Therapeutics, Critical Path for Parkinson's Consortium (CPP), Denali, MJFF, Neuroderm, Sanofi, Sinopia, Sunovion, Roche, Takeda, UCB, Vanqua Bio and Voyager, and is on the advisory board for Acadia, AcureX, AskBio, Amneal, Denali, Sunovion, Roche, and on the Scientific Advisory Board for 4D Pharma, Neuroderm, Sanofi and UCB; Anne-Marie Wills received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, and receives funding of grants by NIA/NIH, Roche/Genentech, Biogen, and their institution participates on Data Safety Monitoring Board or Advisory Board for Ono Pharmaceuticals and Amylyx Pharmaceuticals; Roy N. Alcalay received funding of grants from Parkinson’s Foundation for acting as a Steering Committee Member, receives funding from NIH, Department of Defense, MJFF, the Silverstein Foundation for GBA/PD and received consulting fees from Sanofi, Ono Therapeutics, Avrobio, Takeda, Gain Therapeutics, Merck, GSK, Caraway., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma with a poor prognosis and no established therapy. Recently, encouraging responses to immune checkpoint inhibitors have been reported., Methods: We conducted an investigator-initiated, multicenter, single-group, phase 2 study of the anti-programmed death ligand 1 (PD-L1) agent atezolizumab in adult and pediatric patients with advanced ASPS. Atezolizumab was administered intravenously at a dose of 1200 mg (in patients ≥18 years of age) or 15 mg per kilogram of body weight with a 1200-mg cap (in patients <18 years of age) once every 21 days. Study end points included objective response, duration of response, and progression-free survival according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, as well as pharmacodynamic biomarkers of multistep drug action., Results: A total of 52 patients were evaluated. An objective response was observed in 19 of 52 patients (37%), with 1 complete response and 18 partial responses. The median time to response was 3.6 months (range, 2.1 to 19.1), the median duration of response was 24.7 months (range, 4.1 to 55.8), and the median progression-free survival was 20.8 months. Seven patients took a treatment break after 2 years of treatment, and their responses were maintained through the data-cutoff date. No treatment-related grade 4 or 5 adverse events were recorded. Responses were noted despite variable baseline expression of programmed death 1 and PD-L1., Conclusions: Atezolizumab was effective at inducing sustained responses in approximately one third of patients with advanced ASPS. (Funded by the National Cancer Institute and others; ClinicalTrials.gov number, NCT03141684.)., (Copyright © 2023 Massachusetts Medical Society.)