The common variable immunodeficiency IgM repertoire narrowly recognizes erythrocyte and platelet glycans.

BACKGROUND: Autoimmune cytopenias (AICs) regularly occur in profoundly IgG-deficient patients with common variable immunodeficiency (CVID). The isotypes, antigenic targets, and origin(s) of their disease-causing autoantibodies are unclear. OBJECTIVE: We sought to determine reactivity, clonality, and provenance of AIC-associated IgM autoantibodies in patients with CVID. METHODS: We used glycan arrays, patient erythrocytes, and platelets to determine targets of CVID IgM autoantibodies. Glycan-binding profiles were used to identify autoreactive clones across B-cell subsets, specifically circulating marginal zone (MZ) B cells, for sorting and IGH sequencing. The locations, transcriptomes, and responses of tonsillar MZ B cells to different TH- cell subsets were determined by confocal microscopy, RNA-sequencing, and cocultures, respectively. RESULTS: Autoreactive IgM coated erythrocytes and platelets from many CVID patients with AICs (CVID+AIC). On glycan arrays, CVID+AIC plasma IgM narrowly recognized erythrocytic i antigens and platelet i-related antigens and failed to bind hundreds of pathogen- and tumor-associated carbohydrates. Polyclonal i antigen-recognizing B-cell receptors were highly enriched among CVID+AIC circulating MZ B cells. Within tonsillar tissues, MZ B cells secreted copious IgM when activated by the combination of IL-10 and IL-21 or when cultured with IL-10/IL-21-secreting FOXP3-CD25hi T follicular helper (Tfh) cells. In lymph nodes from immunocompetent controls, MZ B cells, plentiful FOXP3+ regulatory T cells, and rare FOXP3-CD25+ cells that represented likely CD25hi Tfh cells all localized outside of germinal centers. In CVID+AIC lymph nodes, cellular positions were similar but CD25hi Tfh cells greatly outnumbered regulatory cells. CONCLUSIONS: Our findings indicate that glycan-reactive IgM autoantibodies produced outside of germinal centers may contribute to the autoimmune pathogenesis of CVID.

Development of High-Risk Geriatric Polypharmacy Electronic Clinical Quality Measures and a Pilot Test of EHR Nudges Based on These Measures.

BACKGROUND: Inappropriate polypharmacy, prevalent among older patients, is associated with substantial harms. OBJECTIVE: To develop measures of high-risk polypharmacy and pilot test novel electronic health record (EHR)-based nudges grounded in behavioral science to promote deprescribing. DESIGN: We developed and validated seven measures, then conducted a three-arm pilot from February to May 2019. PARTICIPANTS: Validation used data from 78,880 patients from a single large health system. Six physicians were pre-pilot test environment users. Sixty-nine physicians participated in the pilot. MAIN MEASURES: Rate of high-risk polypharmacy among patients aged 65 years or older. High-risk polypharmacy was defined as being prescribed ≥5 medications and satisfying ≥1 of the following high-risk criteria: drugs that increase fall risk among patients with fall history; drug-drug interactions that increase fall risk; thiazolidinedione, NSAID, or non-dihydropyridine calcium channel blocker in heart failure; and glyburide, glimepiride, or NSAID in chronic kidney disease. INTERVENTIONS: Physicians received EHR alerts when renewing or prescribing certain high-risk medications when criteria were met. One practice received a "commitment nudge" that offered a chance to commit to addressing high-risk polypharmacy at the next visit. One practice received a "justification nudge" that asked for a reason when high-risk polypharmacy was present. One practice received both. KEY RESULTS: Among 55,107 patients 65 and older prescribed 5 or more medications, 6256 (7.9%) had one or more high-risk criteria. During the pilot, the mean (SD) number of nudges per physician per week was 1.7 (0.4) for commitment, 0.8 (0.5) for justification, and 1.9 (0.5) for both interventions. Physicians requested to be reminded to address high-risk polypharmacy for 236/833 (28.3%) of the commitment nudges and acknowledged 441 of 460 (95.9%) of justification nudges, providing a text response for 187 (40.7%). CONCLUSIONS: EHR-based measures and nudges addressing high-risk polypharmacy were feasible to develop and implement, and warrant further testing.

Nursing Home Provider Perceptions of Telemedicine for Providing Specialty Consults.

BACKGROUND: Nursing homes (NHs) provide care to a complex patient population and face the ongoing challenge of meeting resident needs for specialty care. A NH telemedicine care model could improve access to remote specialty providers. INTRODUCTION: Little is known about provider interest in telemedicine for specialty consults in the NH setting. The goal of this study was to survey a national sample of NH physicians and advanced practice providers to document their views on telemedicine for providing specialty consults in the NH. MATERIALS AND METHODS: We surveyed physician and advanced practice providers who attended the 2016 AMDA-The Society for Post-Acute and Long-Term Care Medicine Annual Conference about their likelihood of referral to and perceptions of a telemedicine program for providing specialty consults in the NH. RESULTS: We received surveys from 524 of the 1,274 conference attendees for a 41.1% response rate. Respondents expressed confidence in the ability of telemedicine to fill existing service gaps and provide appropriate, timelier care. Providers showed the highest level of interest in telemedicine for dermatology, geriatric psychiatry, and infectious disease. Only 13% of respondents indicated that telemedicine was available for use in one of their facilities. DISCUSSION: There appears to be unmet demand for telemedicine in NHs for providing specialty consults to residents. CONCLUSIONS: The responses of NH providers suggest support for the concept of telemedicine as a modality of care that can be used to offer specialty consults to NH residents.

Perceptions of Nursing Facility Providers on the Utility of Deprescribing.

OBJECTIVE: Potentially inappropriate medications carry significant burden and costs to nursing facility residents and health systems. The goal of this study was to survey nursing facility providers from across the United States to describe the current utilization of deprescribing, and perceptions and desired components of a deprescribing program, in nursing facilities to reduce potentially inappropriate medications. DESIGN/SETTING/PARTICIPANTS/MEASUREMENT: We surveyed health care providers who attended the 2017 AMDA-The Society for Post-Acute and Long-Term Care Medicine Annual Conference-in Phoenix, Arizona. Returned surveys were entered into an electronic database from paper copies. Survey responses were summarized using descriptive statistics. RESULTS: Of the 1,431 conference attendees, 637 surveys were returned for a 45% response rate. Most respondents were physicians (n = 563, 88%). Respondents indicated a strong agreement with the potential for deprescribing to reduce cost to residents and nursing administration time and burden, while disagreeing that deprescribing may be depersonalizing. Respondents indicated clear preference for deprescribing programs to target medications that are no longer indicated and are "high risk," and that such programs should include discussions with the resident. Respondents also agreed that deprescribing programs are successful if the resident, or the resident's family and/or caregivers, reports an improvement in quality of life. CONCLUSION: Among respondents there was a high degree of confidence in the potential impact of deprescribing initiatives, as well as a broad consensus of desired components. This information may increase consultant pharmacist engagement and drive future proactive deprescribing initiatives.

The DE-PHARM Project: A Pharmacist-Driven Deprescribing Initiative in a Nursing Facility.

OBJECTIVE: Many residents with life-limiting illnesses are being prescribed and taking potentially inappropriate medications (PIMs) and questionably beneficial medications either near or at the end of life. These medications can contribute to adverse drug reactions, increase morbidity, and increase unnecessary burden and cost. It is crucial that the process of deprescribing be incorporated into the care of these residents. After developing a clinical pharmacist-driven deprescribing initiative in the nursing facility, the objective of this project was to reduce the number of PIMs via accepted recommendations from the clinical pharmacist to the primary team. DESIGN/SETTING/PARTICIPANTS: The Discussion to Ensure the Patient-centered, Health-focused, prognosis-Appropriate, and Rational Medication regimen (DE-PHARM) quality improvement-approved project was conducted in an urban, academic nursing facility in Pittsburgh, Pennsylvania. The pilot phase occurred between October 2015 and April 2016. To be included in this study, participants had to be a custodial resident of the nursing facility with a previously documented comfort-focused treatment plan. All medications used for the management of chronic comorbid diseases were eligible for review. RESULTS: Forty-seven residents managed by eight different primary teams met inclusion criteria. Thirty-nine recommendations for 23 residents were made by the clinical pharmacist, with an average of 0.82 and range of 0-5 recommendations per resident, respectively. Of those, only 10 (26%) were accepted, 1 (3%) was modified, 3 (7%) were rejected, and 25 (64%) had no response within the 120-day response period. Additionally, two residents died during the project, and one resident was readmitted to the hospital for a prolonged period of time. CONCLUSION: The pilot phase of the DE-PHARM project, a clinical pharmacist-driven deprescribing initiative, was designed and assessed. This project demonstrated the feasibility of such an initiative. Because of the complexity of such a process, special attention must be paid to eligible residents and medications, the need for interprofessional collaboration, and the operational process. This project is ongoing in other nursing facilities in Western Pennsylvania.

Use of Telemedicine to Enhance Pharmacist Services in the Nursing Facility.

OBJECTIVE: To conduct a systematic literature review to determine what telemedicine services are provided by pharmacists and the impact of these services in the nursing facility setting. DATA SOURCES: MEDLINE®, Scopus®, and Embase® databases. STUDY SELECTION: The terms "telemedicine" or "telehealth" were combined by "and" with the terms "pharmacist" or "pharmacy" to identify pharmacists' use of telemedicine. Also, "telepharmacy" was added as a search term. The initial search yielded 322 results. These abstracts were reviewed by two individuals independently, for selection of articles that discussed telemedicine and involvement of a pharmacist, either as the primary user of the service or as part of an interprofessional health care team. Those abstracts discussing the pharmacist service for purpose of dispensing or product preparation were excluded. DATA EXTRACTION: A description of pharmacists' services provided and the impact on resident care. DATA SYNTHESIS: Only three manuscripts met inclusion criteria. One was a narrative proposition of the benefits of using telemedicine by senior care pharmacists. Two published original research studies indirectly assessed the pharmacists' use of telemedicine in the nursing facility through an anticoagulation program and an osteoporosis management service. Both services demonstrated improvement in patient care. CONCLUSION: There is a general paucity of practice-related research to demonstrate potential benefits of pharmacists' services incorporating telemedicine. Telemedicine may be a resource-efficient approach to enhance pharmacist services in the nursing facility and improve resident care.

Physician Perceptions of Consultant Pharmacist Services Associated with an Intervention for Adverse Drug Events in the Nursing Facility.

OBJECTIVE: To assess the importance and performance of consultant pharmacist services delivered before and after an intervention to detect and manage adverse drug events among nursing facility residents. DESIGN: Before and after intervention survey of physicians participating in a randomized, controlled trial. SETTING: Four nonprofit, academically affiliated nursing facilities. PARTICIPANTS: Attending physicians providing nursing facility care who were randomized to intervention or control groups. INTERVENTIONS: Within the intervention arm, consultant pharmacists provided academic detailing in which trained health care professionals visit practicing physicians in their offices and present the most up-to-date clinical information. Physicians responded to alerts from a medication monitoring system, adjudicated system alerts for adverse drug events (ADEs), and provided structured recommendations about ADE management. MAIN OUTCOME MEASURES: We compared physicians' assessments of the importance and performance of consultant pharmacist services before and after the trial intervention in the intervention and control groups. RESULTS: In the intervention group, ratings of importance increased for all 24 survey questions, and 5 of the changes were statistically significant (P < 0.05). In the control group, ratings of importance increased for 16 questions, and none of the changes were statistically significant. In the intervention group, ratings of performance increased for all 24 questions, and 20 of the changes were statistically significant. In the control group, ratings of performance increased for 16 questions, and none of the changes was statistically significant. CONCLUSION: A multifaceted, consultant pharmacist-led intervention comprising academic detailing, computerized decision support, and structured communication framework can improve physicians' assessment of importance and performance of consultant pharmacist services. ABBREVIATIONS: ADE = Adverse drug event, M = Statistically significant mean, RCT = Randomized controlled trial, SBAR = Situation, Background, Discussion, Recommendation, SD = Standard deviation.

A Multicenter Evaluation of Off-Label Medication Use and Associated Adverse Drug Reactions in Adult Medical ICUs.

OBJECTIVE: Prior research indicates that off-label use is common in the ICU; however, the safety of off-label use has not been assessed. The study objective was to determine the prevalence of adverse drug reactions associated with off-label use and evaluate off-label use as a risk factor for the development of adverse drug reactions in an adult ICU population. DESIGN: Multicenter, observational study SETTING: : Medical ICUs at three academic medical centers. PATIENTS: Adult patients (age ≥ 18 yr old) receiving medication therapy. INTERVENTIONS: All administered medications were evaluated for Food and Drug Administration-approved or off-label use. Patients were assessed daily for the development of an adverse drug reaction through active surveillance. Three adverse drug reaction assessment instruments were used to determine the probability of an adverse drug reaction resulting from drug therapy. Severity and harm of the adverse drug reaction were also assessed. Cox proportional hazard regression was used to identify a set of covariates that influenced the rate of adverse drug reactions. MEASUREMENTS AND MAIN RESULTS: Overall, 1,654 patient-days (327 patients) and 16,391 medications were evaluated, with 43% of medications being used off-label. One hundred and sixteen adverse drug reactions were categorized dichotomously (Food and Drug Administration or off-label), with 56% and 44% being associated with Food and Drug Administration-approved and off-label use, respectively. The number of adverse drug reactions for medications administered and the number of harmful and severe adverse drug reactions did not differ for medications used for Food and Drug Administration-approved or off-label use (0.74% vs 0.67%; p = 0.336; 33 vs 31 events, p = 0.567; 24 vs 24 events, p = 0.276). Age, sex, number of high-risk medications, number of off-label medications, and severity of illness score were included in the Cox proportional hazard regression. It was found that the rate of adverse drug reactions increases by 8% for every one additional off-label medication (hazard ratio = 1.08; 95% CI, 1.018-1.154). CONCLUSION: Although adverse drug reactions do not occur more frequently with off-label use, adverse drug reaction risk increases with each additional off-label medication used.

Risk factors for acute kidney injury in older adults with critical illness: a retrospective cohort study.

BACKGROUND: Risk for acute kidney injury (AKI) in older adults has not been evaluated systematically. We sought to delineate the determinants of risk for AKI in older compared with younger adults. STUDY DESIGN: Retrospective analysis of patients hospitalized in July 2000 to September 2008. SETTING & PARTICIPANTS: We identified all adult patients admitted to an intensive care unit (n=45,655) in a large tertiary-care university hospital system. We excluded patients receiving dialysis or a kidney transplant prior to hospital admission and patients with baseline creatinine levels ≥ 4mg/dL, liver transplantation, indeterminate AKI status, or unknown age, leaving 39,938 patients. PREDICTOR: We collected data for multiple susceptibilities and exposures, including age, sex, race, body mass, comorbid conditions, severity of illness, baseline kidney function, sepsis, and shock. OUTCOMES: We defined AKI according to KDIGO (Kidney Disease: Improving Global Outcomes) criteria. We examined susceptibilities and exposures across age strata for impact on the development of AKI. MEASUREMENTS: We calculated area under the receiver operating characteristic curve (AUC) for prediction of AKI across age groups. RESULTS: 25,230 (63.2%) patients were 55 years or older. Overall, 25,120 (62.9%) patients developed AKI (69.2% aged ≥55 years). Examples of risk factors for AKI in the oldest age category (≥75 years) were drugs (vancomycin, aminoglycosides, and nonsteroidal anti-inflammatories), history of hypertension (OR, 1.13; 95% CI, 1.02-1.25), and sepsis (OR, 2.12; 95% CI, 1.68-2.67). Fewer variables remained predictive of AKI as age increased and the model for older patients was less predictive (P<0.001). For the age categories 18 to 54, 55 to 64, 65 to 74, and 75 years or older, AUCs were 0.744 (95% CI, 0.735-0.752), 0.714 (95% CI, 0.702-0.726), 0.706 (95% CI, 0.693-0.718), and 0.673 (95% CI, 0.661-0.685), respectively. LIMITATIONS: Analysis may not apply to non-intensive care unit patients. CONCLUSIONS: The likelihood of developing AKI increases with age; however, the same variables are less predictive for AKI as age increases. Efforts to quantify risk for AKI may be more difficult in older adults.

Potentially suboptimal prescribing for older veteran nursing home patients with dementia.

BACKGROUND: Nursing home patients with dementia may be more likely to suffer adverse drug events from suboptimal prescribing. Previous studies have not used national samples, nor have they examined multiple types of suboptimal prescribing by dementia severity. OBJECTIVE: To examine the prevalence of and factors associated with potentially suboptimal prescribing in older veteran nursing home patients with dementia. METHODS: This is a retrospective descriptive study of 1303 veterans 65 years or older admitted between January 1, 2004, and June 30, 2005, with dementia for long stays (90+ days) to 133 Veterans Affairs Community Living Centers. Dementia severity was determined by the Cognitive Performance Scale and functional status dependences. RESULTS: Overall, 70.2% with mild-moderate dementia (n = 1076) had underuse because they did not receive an acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate use because of a drug-disease or drug-drug-disease interaction. Of the 227 with severe dementia, 36.1% had overuse by receiving an AChEI or lipid-lowering or other agents, and 25.1% had evidence of inappropriate use as a result of a drug-disease or drug-drug interaction. Multinomial logistic regression analyses among those with mild to moderate dementia identified that living in the South versus other regions was the single factor associated with all 3 types of suboptimal prescribing. In those with severe dementia, antipsychotic use was associated with all 3 suboptimal prescribing types. CONCLUSIONS: Potentially suboptimal prescribing was common in older veteran nursing home patients with dementia. Clinicians should develop a heightened awareness of these problems. Future studies should examine associations between potentially suboptimal prescribing and health outcomes in patients with dementia.

Office frenotomy for neonates: resolving dysphagia, parental satisfaction and cost-effectiveness.

OBJECTIVE: To determine parental satisfaction and cost-effectiveness of having a frenotomy performed in the office setting versus in the operating room under general anesthesia. METHOD: After obtaining IRB approval at The Children's Hospital of Philadelphia (CHOP), we performed a retrospective chart review of patients having a frenotomy in the office between 2003-2008. 55 patients met the criteria and 25 were consented and their parents interviewed. CONCLUSION: All participants reported an improvement in feeding within one day and up to two weeks following the procedure. Parents also reported being somewhat satisfied to very satisfied with having the frenotomy performed in the office versus under general anesthesia. There were no complications reported. Performing the frenotomy in the office provided patients with satisfaction as well as cost savings. The surgical fee for a frenotomy in the office is $850 and is the same as if the procedure is performed in the operating room. Performing a frenotomy under general anesthesia includes extra cost which consists of an anesthesia fee of $500-$900 and hospital charges ranging from $500-$8,000. Performing the frenotomy in the office on our 25 patients has resulted in a cost savings of more than $240,000 and the avoidance of general anesthesia in the first few weeks of life. Office frenotomy should be considered in children with ankyloglossia who present with difficulty nursing in the first week of life.

Factors Associated With the Ability of US Nursing Homes to Accept Residents With Severe Obesity.

OBJECTIVES: Severe obesity in nursing home (NH) residents is associated with specialized care needs, limited mobility, and challenges in daily living. The COVID-19 pandemic strained NH resources and exacerbated staffing shortages. This study aimed to assess the ability of US NHs to accept and care for residents with severe obesity post-COVID, as well as associated NH factors. DESIGN: Cross-sectional nationwide survey of NH administrators (2021-2022). SETTING AND PARTICIPANTS: 290 NHs from a national sample (n = 224) and a targeted sample in Massachusetts and New Jersey (n = 66). METHODS: A survey designed to assess how NHs approach admitting and caring for people with severe obesity before and after COVID was fielded from 2021 to 2022. Responses were linked to facility information from the Certification and Survey Provider Enhanced Reports, Minimum Data Set, Nursing Home Compare, Area Health Resources File, and US Diabetes Surveillance System. Multivariable logistic regression was used to assess the effect of organizational and survey response variables. RESULTS: Of the 2503 surveys sent to US NHs, 1923 were sent to the national NH stratified sample, and 580 were sent to the MA/NJ sample. Overall, 12% (301 of 2503) of NHs surveyed responded. The response rates were similar between the 2 samples. Of 290 NHs with complete data, 34% reported being unlikely to accept residents with severe obesity after COVID-19, compared with 25% before the pandemic (P < .001). The main barriers to acceptance were staffing shortages and difficulties meeting equipment and space needs. NHs with higher proportions of Black residents were more likely to admit individuals with severe obesity. CONCLUSIONS AND IMPLICATIONS: The decline in acceptance of residents with severe obesity during and after COVID-19 highlights potential challenges that this population faces in accessing care. Our results also raise concerns that an intersection of disparities may exist in Black patients with severe obesity.

Use of HIT for adverse event reporting in nursing homes: barriers and facilitators.

BACKGROUND & OBJECTIVE: Approximately 8 million adverse events occur annually in nursing homes (NHs). The focus of this research is to determine barriers and health information technology (HIT)-related facilitators to adverse event reporting among U.S. NHs. METHODS: Surveys were returned by 399 nursing home administrators using a mailed survey approach. Respondents were asked to report on their adverse event reporting processes focusing on barriers and role of HIT facilitators. RESULTS: About 15% of NHs had computerized entry by the nurse on the unit and almost 18% used no computer technology to track, monitor, or maintain adverse event data. One-third of nursing directors conducted data analysis "by-hand." NHs without HIT were more likely to not be accredited (p = 0.04) and not part of a chain/corporation (p = 0.03). Two of the top three barriers focused on fears of reporting as a barrier. CONCLUSIONS: This study found numerous barriers and few HIT-related facilitators to assist with adverse event reporting. Improvements in facilitating adverse event reporting through the use of HIT approaches may be warranted.

Utility of an adverse drug event trigger tool in Veterans Affairs nursing facilities.

OBJECTIVE: To determine the utility (i.e., positive predictive value [PPV] and time requirement) of an adverse drug event (ADE) trigger tool in Veterans Affairs (VA) nursing facilities and to describe the most common types of potential ADEs detected with the trigger tool. DESIGN: Retrospective chart review. SETTING/PATIENTS: Veterans residing in three VA nursing facilities between September 29, 2010, and October 29, 2010. MEASUREMENT: We used the Institute for Healthcare Improvement-endorsed nursing facility ADE trigger tool, modified to enhance its clinical relevance to detect potential ADEs. Electronic medical records were screened to identify residents with one or more abnormal laboratory values specified in the trigger tool. MAIN OUTCOME MEASURES: A potential ADE was defined as the concurrent administration of medication that could cause the abnormal laboratory value. An overall PPV, or proportion of residents with an abnormal laboratory value who had a potential ADE, and average time required to complete each trigger tool assessment, were calculated. RESULTS: Among 321 veterans, 50.5% (n = 162) had at least one abnormal laboratory value contained in the trigger tool. Ninety-nine potential ADEs involving 146 medications were detected in 65 veterans. The overall PPV of the ADE trigger tool was 40.1% (65/162), and the average time to complete resident assessments was 8.8 (standard deviation ± 5.7) minutes. The most common potential ADEs were acute kidney injury (n = 30 residents), hypokalemia (n = 18), hypoglycemia (n = 13), and hyperkalemia (n = 10). CONCLUSIONS: The modified nursing facility trigger tool was shown to be an effective and efficient method for detecting potential ADEs.

Paying A Heavy Price: Costs of Care for People with Severe Obesity in Nursing Homes.

BACKGROUND AND OBJECTIVES: The prevalence of resident obesity in nursing homes has increased dramatically from 22% to 28% between 2005 and 2015. To provide care for people with obesity, nursing homes have changed their admissions, staffing, and equipment, but underlying these changes are increased resources and financial costs of care. The purpose of this study is to describe nursing home organizational aspects of caring for older adults with obesity, with a focus on economic factors, from the perspective of nursing home staff and leadership. RESEARCH DESIGN AND METHODS: This qualitative study used descriptive approaches; data were collected through semi-structured telephone interviews. Of 77 nursing home staff and leaders identified as potential study participants, 6 were ineligible, and 71 participated in the study through interviews conducted from 2019 to 2022. RESULTS: Four primary themes described the issues surrounding cost of care for obesity in nursing homes: inefficient and risky use of staff time in a setting of persistent staff shortage, expensive and unique equipment needs, inadequate general reimbursement with an absence of obesity-specific reimbursement supplements, and competing short and long-term management solutions. DISCUSSION AND IMPLICATIONS: This qualitative study of nursing home staff and leadership underscores a need for improved approaches to funding obesity care within existing nursing payment models. The increasing prevalence of obesity and the burden of the costs of obesity care for nursing homes will escalate this need over the coming decade.

Human T follicular helper clones seed the germinal center-resident regulatory pool.

The mechanisms by which FOXP3+ T follicular regulatory (Tfr) cells simultaneously steer antibody formation toward microbe or vaccine recognition and away from self-reactivity remain incompletely understood. To explore underappreciated heterogeneity in human Tfr cell development, function, and localization, we used paired TCRVA/TCRVB sequencing to distinguish tonsillar Tfr cells that are clonally related to natural regulatory T cells (nTfr) from those likely induced from T follicular helper (Tfh) cells (iTfr). The proteins iTfr and nTfr cells differentially expressed were used to pinpoint their in situ locations via multiplex microscopy and establish their divergent functional roles. In silico analyses and in vitro tonsil organoid tracking models corroborated the existence of separate Treg-to-nTfr and Tfh-to-iTfr developmental trajectories. Our results identify human iTfr cells as a distinct CD38+, germinal center-resident, Tfh-descended subset that gains suppressive function while retaining the capacity to help B cells, whereas CD38- nTfr cells are elite suppressors primarily localized in follicular mantles. Interventions differentially targeting specific Tfr cell subsets may provide therapeutic opportunities to boost immunity or more precisely treat autoimmune diseases.

Use of antipsychotics among older residents in VA nursing homes.

BACKGROUND: Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Affairs (VA) nursing homes [ie, Community Living Centers (CLCs)], we assessed the prevalence and risk factors for antipsychotic use in older residents of VA CLCs. METHODS: This cross-sectional study included 3692 Veterans age 65 or older who were admitted between January 2004 and June 2005 to one of 133 VA CLCs and had a stay of ≥90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (eg, schizophrenia, dementia with psychosis). We used multivariable logistic regression and generalized estimating equations to identify factors independently associated with antipsychotic receipt. RESULTS: Overall, 948/3692(25.7%) residents received an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior [odds ratio (OR)=2.74, 95% confidence interval (CI), 2.04-3.67] and polypharmacy (9+ drugs; OR=1.84, 95% CI, 1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR=1.37, 95% CI, 1.14-1.66), anxiolytic/hypnotics (OR=2.30, 95% CI, 1.64-3.23), or drugs for dementia (OR=1.52, 95% CI, 1.21-1.92). Those residing in Alzheimer/dementia special care units were also more likely to receive an antipsychotic (OR=1.66, 95% CI, 1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR=1.10, 95% CI, 0.82-1.47). CONCLUSIONS: Antipsychotic use is common among VA nursing home residents aged 65 and older, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing.

Clinical decision support to promote safe prescribing to women of reproductive age: a cluster-randomized trial.

BACKGROUND: Potentially teratogenic medications are frequently prescribed without provision of contraceptive counseling. OBJECTIVE: To evaluate whether computerized clinical decision support (CDS) can increase primary care providers' (PCPs') provision of family planning services when prescribing potentially teratogenic medications. DESIGN: Cluster-randomized trial conducted in one academic and one community-based practice between October of 2008 and April of 2010. PARTICIPANTS/INTERVENTIONS: Forty-one PCPs were randomized to receive one of two types of CDS which alerted them to risks of medication-induced birth defects when ordering potentially teratogenic medications for women who may become pregnant. The 'simple' CDS provided a cautionary alert; the 'multifaceted' CDS provided tailored information and links to a structured order set designed to facilitate safe prescribing. Both CDS systems alerted PCPs about medication risk only once per encounter. MAIN MEASURES: We assessed change in documented provision of family planning services using data from 35,110 encounters and mixed-effects models. PCPs completed surveys before and after the CDS systems were implemented, allowing assessment of change in PCP-reported counseling about the risks of medication-induced birth defects and contraception. KEY RESULTS: Both CDS systems were associated with slight increases in provision of family planning services when potential teratogens were prescribed, without a significant difference in improvement by CDS complexity (p = 0.87). Because CDS was not repeated, 13% of the times that PCPs received CDS they substituted another potential teratogen. PCPs reported significant improvements in several counseling and prescribing practices. The multifaceted group reported a greater increase in the number of times per month they discussed the risks of medication use during pregnancy (multifaceted: +4.9 ± 7.0 vs. simple: +0.8 ± 3.2, p = 0.03). The simple CDS system was associated with greater clinician satisfaction. CONCLUSIONS: CDS systems hold promise for increasing provision of family planning services when fertile women are prescribed potentially teratogenic medications, but further refinement of these systems is needed.

Falls prediction using the nursing home minimum dataset.

OBJECTIVE: The purpose of the study was to develop and validate a model to predict the risk of experiencing a fall for nursing home residents utilizing data that are electronically available at the more than 15 000 facilities in the United States. MATERIALS AND METHODS: The fall prediction model was built and tested using 2 extracts of data (2011 through 2013 and 2016 through 2018) from the Long-term Care Minimum Dataset (MDS) combined with drug data from 5 skilled nursing facilities. The model was created using a hybrid Classification and Regression Tree (CART)-logistic approach. RESULTS: The combined dataset consisted of 3985 residents with mean age of 77 years and 64% female. The model's area under the ROC curve was 0.668 (95% confidence interval: 0.643-0.693) on the validation subsample of the merged data. DISCUSSION: Inspection of the model showed that antidepressant medications have a significant protective association where the resident has a fall history prior to admission, requires assistance to balance while walking, and some functional range of motion impairment in the lower body; even if the patient exhibits behavioral issues, unstable behaviors, and/or are exposed to multiple psychotropic drugs. CONCLUSION: The novel hybrid CART-logit algorithm is an advance over the 22 fall risk assessment tools previously evaluated in the nursing home setting because it has a better performance characteristic for the fall prediction window of ≤90 days and it is the only model designed to use features that are easily obtainable at nearly every facility in the United States.

Safety culture of nursing homes: opinions of top managers.

BACKGROUND: Examining the perception of patient safety culture (PSC) of top managers in health care settings is important because their orientation to PSC can have a large influence on the facility. PURPOSES: In this research, the perception of PSC of nursing home administrators (NHAs) and directors of nursing (DONs) is examined. METHODOLOGY/APPROACH: Primary data were collected to examine the opinions of NHAs and DONs regarding PSC. Information was collected from a large nationally representative sample of 4,000 nursing homes. The Nursing Home Survey on Patient Safety Culture survey instrument was used as a measure of PSC. This has 12 domains and 38 items. Bias indexes, intraclass correlation coefficients, and Pearson's product-moment correlation coefficients of the differences between NHA and DON item scores were examined. FINDINGS: Using a 0-100 scale, most scores fell into the 55-80 range. Higher scores represent a higher (more favorable) PSC. Agreement between the NHAs and DONs was excellent in 10 items, good in 15 items, moderate in 4 items, and poor in 8 items. Of the four largest differences in scores, the NHA scores were higher than the DON scores for 1 item, and DON scores were higher than the NHA scores for 3 items. IMPLICATIONS: The overall perception from both NHAs and DONs appear to represent a somewhat "positive" outlook from these top managers on their institution's PSC. However, NHAs in general report higher scores than DONs do. The areas of divergence between these top managers are further discussed, with a view toward directing future patient safety investigations and initiatives in nursing homes.