Real-World Use, Safety, and Patient Experience of 20% Subcutaneous Immunoglobulin for Primary Immunodeficiency Diseases.

INTRODUCTION: The CORE study aimed to provide a detailed understanding of real-world immune globulin subcutaneous (human) 20% solution (Ig20Gly) utilization in patients with primary immunodeficiency diseases (PIDs) in Germany and Switzerland. METHODS: Patients with PIDs receiving a stable dose of any subcutaneous immunoglobulin for ≥ 3 months before enrollment were eligible for this multicenter (n = 5), phase 4, non-interventional, prospective, longitudinal cohort study. Besides baseline demographics and clinical characteristics, Ig20Gly utilization and safety data, and patient-reported outcomes (Life Quality Index/Treatment Satisfaction Questionnaire for Medication) were collected at baseline, 6 and 12 months. Statistical analysis was descriptive. RESULTS: Overall, 36 patients provided data at baseline [69.4% female; mean age: 41.6 years (7-78 years)]. Totals of 23 and 26 patients attended 6- and 12-month visits, respectively; 16 attended all three visits. One patient withdrew consent before 6-month follow-up. Median maximum infusion rates of Ig20Gly at baseline, 6 months, and 12 months were 26.7, 24.5, and 40.0 mL/h, respectively (10-60 mL/h). Infusion and dosing parameters remained consistent across time points: patients used a median of two infusion sites, primarily the abdomen, and all patients used an infusion pump; all but one infused at home and most self-administered Ig20Gly (80.8-83.3%) at once-weekly intervals (69.2-73.9%). During follow-up, 10 adverse events were reported: none were rated serious, while 2 were considered probably related to Ig20Gly. Total patient-reported outcome scores remained high throughout the study. CONCLUSION: The CORE study provides real-world evidence of the flexibility, feasibility, safety, and tolerability of Ig20Gly infusions, at mostly weekly intervals, over 1 year in patients with PIDs. TRIAL REGISTRATION: German Clinical Trials Register, DRKS00014562. Registered April 9, 2018, https://drks.de/search/en/trial/DRKS00014562.

Primary immunodeficiency diseases are rare diseases that make patients more likely to develop infections than the general population. Many patients with primary immunodeficiency diseases do not produce enough antibodies, which are an important part of the immune system that fight infection. Replacing antibodies is the main way to treat primary immunodeficiency diseases and reduce the risk of infection. Ig20Gly is a type of medication used to replace antibodies and treat primary immunodeficiency diseases. Patients receive Ig20Gly through a needle inserted under the skin and can learn to do this themselves at home. Ig20Gly can be delivered more quickly than other antibody treatments that are less concentrated. CORE was a study of 36 patients (children and adults) taking Ig20Gly for primary immunodeficiency diseases for 1 year in Germany and Switzerland. The aim of the study was to understand how patients use and experience Ig20Gly as part of their normal treatment. In this study, nearly all patients received Ig20Gly treatment at home, and most patients gave Ig20Gly to themselves once a week. A few patients developed serious bacterial infections while being treated with Ig20Gly, and patients were generally satisfied with the treatment. Overall, the CORE study describes how patients with primary immunodeficiency diseases use Ig20Gly in their daily lives, and shows that Ig20Gly treatment can be tailored to suit each patient's needs. Information from this study will help doctors to support patients in making decisions about their treatment.

Impact of star ratings on Medicare health plan enrollment: A systematic literature review.

BACKGROUND: The Medicare star ratings program was developed by the Centers for Medicare and Medicaid Services in 2007 as an approach to evaluate health plan performance and quality. OBJECTIVE: This study aimed to identify and narratively describe studies that attempted to quantitatively assess the impact that Medicare star ratings have on health plan enrollment. METHODS: A systematic literature review (SLR) was conducted of PubMed MEDLINE, Embase, and Google to identify articles that quantitatively assessed the impact of Medicare star ratings on health plan enrollment. Inclusion criteria consisted of studies that conducted quantitative analyses to estimate the potential impact. Exclusion criteria consisted of qualitative studies and studies that did not directly assess plan enrollment. RESULTS: This SLR identified 10 studies that sought to measure the impact of Medicare star ratings on plan enrollment. Nine of the studies found that plan enrollment increased in accordance with increases in star ratings or that plan disenrollment increased with decreases in star ratings. One study conducted of data before the implementation of the Medicare quality bonus payment found contradictory results from one year to the next, whereas all the studies that assessed data after implementation found increases in enrollment in accordance to increases in star ratings or increases in disenrollment for decreases in star ratings. One concerning finding from some of the articles included in the SLR is that increases in star ratings had less of an impact on enrollment in higher-rated plans for ethnic and racial minorities and older adults. CONCLUSIONS: Increases in Medicare star ratings led to statistically significant increases in health plan enrollment and decreases in health plan disenrollment. Future studies are needed to assess whether this increase has a causal association or is caused by additional factors outside of or in addition to increases in overall star rating.

Real-World Evidence of Tolerability of 20% Subcutaneous Immunoglobulin Treatment.

PURPOSE: The safety and efficacy of subcutaneous immune globulin 20% (human) solution (Ig20Gly) were demonstrated in clinical trials. However, real-world evidence of the tolerability of self-administered Ig20Gly in elderly patients is lacking. We describe real-world patterns of Ig20Gly usage for 12 months in patients with primary immunodeficiency diseases (PIDD) in the USA. METHODS: This retrospective chart review of longitudinal data from 2 centers included patients aged ≥ 2 years with PIDD. Ig20Gly administration parameters, tolerability, and usage patterns were assessed at initial and subsequent 6- and 12-month infusions. RESULTS: Of 47 enrolled patients, 30 (63.8%) received immunoglobulin replacement therapy (IGRT) within 12 months before starting Ig20Gly, and 17 (36.2%) started IGRT de novo. Patients were predominantly White (89.1%), female (85.1%), and elderly (aged > 65 years, 68.1%; median age = 71.0 years). Most adults received at-home treatment during the study, and most self-administered at 6 months (90.0%) and 12 months (88.2%). Across all time points, infusions were administered at a mean rate of 60-90 mL/h/infusion, using a mean of 2 sites per infusion, on a weekly or biweekly frequency. No emergency department visits occurred, and hospital visits were rare (n = 1). Forty-six adverse drug reactions occurred in 36.4% of adults, mostly localized site reactions; none of these or any adverse events led to treatment discontinuation. CONCLUSION: These findings demonstrate tolerability and successful self-administration of Ig20Gly in PIDD, including elderly patients and patients starting IGRT de novo.

Sublingual immunotherapy persistence and adherence in real-world settings: A systematic review.

BACKGROUND: Sublingual immunotherapy (SLIT) adherence in the literature is often evaluated in closely monitored trials that may impact patient behavior; real-world SLIT adherence is relatively unknown. This systematic review intends to assess SLIT adherence in studies that reflect real-world settings. METHODS: A literature search of PubMed, Embase, Cochrane, Web of Science, and Scopus for real-world studies examining SLIT adherence was performed. Monitored clinical trials were excluded. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow-up and "adherence" as persistence in accordance with prescribed SLIT dose, dosing schedule, and duration. Article quality was assessed using a modified Newcastle-Ottawa scale and then converted to AHRQ standards (good, fair, and poor). RESULTS: The search yielded 1596 nonduplicate abstracts, from which 32 articles (n = 63,683 patients) met criteria. Twenty-six (81%) studies reported persistence rates ranging from 7.0% to 88.7%, and 18 (56%) reported adherence rates ranging from 9.6% to 97.0%. Twenty-one (66%) studies surveyed reasons for discontinuing SLIT. All studies were Oxford level of evidence 2b and of good (n = 12) to fair (n = 20) quality. CONCLUSION: Reported rates of real-world SLIT persistence and adherence varied widely by study methodology (e.g., follow-up duration, objective vs. subjective assessment). Studies with longer follow-up generally reported lower rates; 3-year persistence ranged from 7% to 59.0% and 3-year adherence from 9.6% to 49.0%. Future studies of SLIT adherence would benefit from following concordant definitions of persistence/adherence and standardized reporting metrics.

Systematic review of real-world persistence and adherence in subcutaneous allergen immunotherapy.

BACKGROUND: Given that subcutaneous immunotherapy (SCIT) adherence in the literature is often studied in closely monitored trials, few studies report real-world SCIT adherence. The purpose of this review is to assess SCIT adherence in real-world settings. METHODS: A literature search of PubMed, Embase, Cochrane Library, Web of Science, and Scopus for real-world studies examining SCIT adherence was performed. Paired investigators independently reviewed all articles. For this review, "persistence" was defined as continuing therapy and not being lost to follow-up after initiating SCIT, and "adherence" defined as persistence in accordance with prescribed SCIT dose, dosing schedule, and duration. Article quality was first assessed using a modified Newcastle-Ottawa scale and then converted to Agency for Healthcare Research and Quality standards (good, fair, and poor). RESULTS: The search yielded 1596 nonduplicate abstracts, from which 17 articles (n = 263,221 patients) met inclusion criteria. Fourteen (82%) studies reported persistence rates, ranging from 16.0% to 93.7%. Seven (41%) studies reported adherence rates, ranging from 15.1% to 99%. Five (29%) studies (n = 416 patients) collected original data on reasons for discontinuing SCIT, of which inconvenience was most cited. All studies were Oxford level of evidence 2b and of good (n = 10) to fair (n = 7) quality. CONCLUSION: Real-world SCIT persistence and adherence rates are poor, with the majority of included studies reporting rates <80%; however, they range widely, explained in part by inter-study differences in measuring and reporting adherence-related findings. Future studies on SCIT adherence may benefit from following concordant definitions of persistence and adherence in addition to standardized reporting metrics.

Transitioning subcutaneous immunoglobulin 20% therapies in patients with primary and secondary immunodeficiencies: Canadian real-world study.

BACKGROUND: Real-world data on transitioning to Immune Globulin Subcutaneous (Human) 20% solution (Ig20Gly) are limited. This study aimed to assess infusion parameters and experience of patients with primary (PID) or secondary immunodeficiencies (SID) transitioning to Ig20Gly in clinical practice in Canada. METHODS: Patients with PID or SID who received subcutaneous immunoglobulin (SCIG) for ≥ 3 months before transitioning to Ig20Gly were eligible for this multicenter (n = 6), phase 4, non-interventional, prospective, single-arm study. Ig20Gly infusion parameters, dosing, and adverse events were collected from patient medical records at Ig20Gly initiation and 3, 6, and 12 months post-initiation. Patient satisfaction and quality of life were assessed 12 months post-initiation using validated questionnaires. RESULTS: The study included 125 patients (PID, n = 60; SID, n = 64; PID + SID, n = 1). Median volume per infusion was 30.0 ml at initiation, and 40.0 ml at 6 and 12 months post-initiation. Most patients administered Ig20Gly weekly and used two infusion sites (primarily abdomen). At each time point, median infusion duration was ≤ 1 h. At 12 months, 61% of infusions were administered via a pump and 39% manually. Headache and infusion-site reactions were the most reported adverse events of interest. Patients expressed overall satisfaction with Ig20Gly at 12 months post-initiation, with all respondents indicating they would like to continue Ig20Gly. CONCLUSIONS: This study provides a detailed description of Ig20Gly infusion parameters, tolerability, and quality of life in clinical practice among patients with PID or SID switching to Ig20Gly from another SCIG and confirms the feasibility of infusing Ig20Gly via pump or manual administration. Trial registration NCT03716700, Registered 31 August 2018, https://clinicaltrials.gov/ct2/show/NCT03716700.

Subcutaneous immunoglobulin use in immunoglobulin-naive patients with primary immunodeficiency: a systematic review.

Aim: Identify and describe published literature on the use of subcutaneous immunoglobulin (SCIG) as initial immunoglobulin (IG)-replacement therapy for patients with primary immunodeficiency diseases (PID). Methods: We systematically identified and summarized literature in MEDLINE, Embase, BioSciences Information Service and Cochrane Library assessing efficacy/effectiveness, safety/tolerability, health-related quality-of-life (HRQoL) and dosing regimens of SCIG for IG-naive patients with PID. Results: Sixteen studies were included. In IG-naive patients, SCIG managed/reduced infections and demonstrated similar pharmacokinetic parameters to IG-experienced patients; adverse events were mostly minor injection-site pain or discomfort. Three studies reported improvements in HRQoL. Quality of studies was difficult to assess due to limited reporting. Conclusion: Although studies were lacking, available data suggest IG-naive and IG-experienced patients initiating SCIG likely have similar outcomes.

Effective recruitment strategies in an exercise trial for patients with fibromyalgia.

BACKGROUND: Recruitment of fibromyalgia populations into long-term clinical trials involving exercise interventions is a challenge. We evaluated the cost and randomization yields of various recruitment methods used for a fibromyalgia trial in an urban setting. We also investigated differences in participant characteristics and exercise intervention adherence based on recruitment source. METHODS: We recruited individuals with fibromyalgia in the greater Boston area to a randomized controlled trial (RCT) using six recruitment strategies: newspaper advertisements, web advertisements, flyers, clinic referrals, direct mailing to patients in a clinic database, and word of mouth. We used the American College of Rheumatology 1990 and 2010 diagnostic criteria to screen and enroll participants. During an initial phone call to an interested participant, the study staff asked how they heard about the study. In this study, we compared the cost and yield of the six recruitment strategies as well as baseline characteristics, adherence, and attendance rates of participants across strategies. RESULTS: Our recruitment resulted in 651 prescreens, 272 screening visits, and 226 randomized participants. Advertisements in a local commuter newspaper were most effective, providing 113 of 226 randomizations, albeit high cost ($212 per randomized participant). Low-cost recruitment strategies included clinical referrals and web advertisements, but they only provided 32 and 16 randomizations. Community-based strategies including advertisement and flyers recruited a more racially diverse participant sample than clinic referrals and mailing or calling patients. There was no evidence of difference in adherence among participants recruited from various strategies. CONCLUSIONS: Newspaper advertisement was the most effective and most expensive method per randomized participant for recruiting large numbers of individuals with fibromyalgia in an urban setting. Community-based strategies recruited a more racially diverse cohort than clinic-based strategies. TRIAL REGISTRATION: ClinicalTrials.gov NCT01420640 . Registered on 19 August 2011.

Rituximab for treatment of refractory multiple sclerosis relapses during pregnancy.

Case Summary: While multiple sclerosis (MS) disease activity declines during pregnancy, there are situations where MS relapses in pregnant women do occur. Mild relapses may be managed with close observation, but severe refractory relapses may require more aggressive management. We describe two cases of rituximab used for severe, refractory multiple sclerosis relapses during pregnancy. Rituximab did not appear to complicate either pregnancy and there were no further relapses for either women. Rituximab should not be overlooked in rare refractory cases, such as the rebound relapses sometimes seen following the discontinuation of lymphocyte-sequestering disease-modifying therapies.

Patients with abrupt early-onset OCD due to PANS tolerate lower doses of antidepressants and antipsychotics.

OBJECTIVE: To characterize drug tolerability in pediatric patients with an abrupt-onset of obsessive-compulsive disorder (OCD) meeting criteria for pediatric acute-onset neuropsychiatric syndrome (PANS). METHODS: We reviewed charts of 188 consecutive patients with PANS seen in the PANS clinic, collecting starting, side effect, and tolerated doses, as well as side effect profile for each antidepressant and antipsychotic trial. RESULTS: Of 188 included patients: 57% had trials of antidepressants and/or antipsychotics. Patients prescribed psychotropics were older at PANS onset (mean 9.5 vs 7.1 years, p < 0.01) and had had a longer delay before presenting to clinic (median 1.4 vs 0.5 years, p < 0.01). Antidepressant indications (n = 146) were OCD (48%), anxiety (44%), and depression (32%). Antipsychotic indications (n = 119) were aggression (34%), psychotic symptoms (28%), and OCD (24%). Side effects requiring medication change occurred in 54% of patients: in 38% of antidepressant trials and 49% of antipsychotic trials. Antidepressants' most common side effects were anxiety, agitation, aggression, and akathisia. Antipsychotics' most common side effects were dystonia, aggression, self-injurious behavior, and movement abnormality. Side effects were common at doses lower than the suggested starting doses for these medications. Patients tolerated antidepressants and antipsychotics when doses were low. CONCLUSION: When antidepressants and antipsychotics are prescribed to patients with PANS, intolerable side effects were noted at doses lower than or equal to suggested starting doses. Patients with PANS can benefit from these therapies. However, when treating these patients, clinicians are advised to start with significantly lower doses than they might use in other disorders.

Proliferative potential and response to nivolumab in clear cell renal cell carcinoma patients.

Background: Biomarkers predicting immunotherapy response in metastatic renal cell cancer (mRCC) are lacking. PD-L1 immunohistochemistry is a complementary diagnostic for immune checkpoint inhibitors (ICIs) in mRCC, but has shown minimal clinical utility and is not used in routine clinical practice. Methods: Tumor specimens from 56 patients with mRCC who received nivolumab were evaluated for PD-L1, cell proliferation (targeted RNA-seq), and outcome. Results: For 56 patients treated with nivolumab as a standard of care, there were 2 complete responses and 8 partial responses for a response rate of 17.9%. Dividing cell proliferation into tertiles, derived from the mean expression of 10 proliferation-associated genes in a reference set of tumors, poorly proliferative tumors (62.5%) were more common than moderately (30.4%) or highly proliferative (8.9%) counterparts. Moderately proliferative tumors were enriched for PD-L1 positive (41.2%), compared to poorly proliferative counterparts (11.4%). Objective response for moderately proliferative (29.4%) tumors was higher than that of poorly (11.4%) proliferative counterparts, but not statistically significant (p = .11). When cell proliferation and negative PD-L1 tumor proportion scores were combined statistically significant results were achieved (p = .048), showing that patients with poorly proliferative and PD-L1 negative tumors have a very low response rate (6.5%) compared to moderately proliferative PD-L1 negative tumors (30%). Conclusions: Cell proliferation has value in predicting response to nivolumab in clear cell mRCC patients, especially when combined with PD-L1 expression. Further studies which include the addition of progression-free survival (PFS) along with sufficiently powered subgroups are required to further support these findings.

Predictors of outcomes in patients with gastric cancer treated with contemporary multimodality strategies-a single institution experience.

BACKGROUND: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. There is paucity in the literature for direct comparison of various practices. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study in patients with gastric cancer who had multimodality treatment for non-metastatic gastric cancer. METHODS: We gathered clinical data (patient demographics, pathology reports, type of surgical intervention, chemotherapy, and radiation therapy) for patients diagnosed with gastric adenocarcinoma who underwent gastrectomy at five sites from 2010-2017 using Electronic Health Records and California Cancer Registry databases. Medical chart reviews were conducted to validate patient outcomes. We performed multivariate Cox regression analyses to determine predictors for cancer recurrence and survival. We also performed logistic regression analyses to determine predictors of positive resection margins and hospitalization. RESULTS: One hundred and sixteen patients met eligibility criteria to be included. Mean age was 65.7±11.6 years. About 65.5% were male. The most common ethnicities were Asian (44.0%) and Caucasian (37.9%). About 58.6% of the patients had localized disease (defined as pT1-3, pN0) and the remaining 41.4% had loco-regional disease (i.e., pT4 or pN+). About 41.4% of the tumors were diffuse, 27.6% intestinal, 12.0% mixed, and 19.0% unknown histology. Surgery included laparoscopic (94.8%) and open gastrectomy (5.2%). Chemotherapy and radiation therapy were given in 51.7% and 19.0% of the patients, respectively. After a median follow-up time of 19 months after gastrectomy, 16.4% of patients had recurrence and 19.8% had died. Patients who had loco-regional tumors were more likely to have recurrence and death than those who had localized tumors (hazard ratios =7.0, P=0.0228 for recurrence and hazard ratios =3.3, P=0.0160 for death). Positive resection margins were seen in 9% of the patients and were associated with diffuse histology (odds ratio =6.6, P=0.0207). Hospitalization within six months of gastrectomy was seen in 22% of the patients. Peri-operative chemotherapy was the only significant predictor for re-hospitalization (odds ratio =3.5, P=0.0415). CONCLUSIONS: In this contemporary cohort of patients with localized gastric cancer, only the pathological stage was significantly associated with survival while positive resection margins were associated with diffuse histology. Closer monitoring of patients undergoing perioperative chemotherapy within 6 months of surgery is warranted based on our observation of higher rate of re-hospitalization.

Designing Ambient Narrative-Based Interfaces to Reflect and Motivate Physical Activity.

Numerous technologies now exist for promoting more active lifestyles. However, while quantitative data representations (e.g., charts, graphs, and statistical reports) typify most health tools, growing evidence suggests such feedback can not only fail to motivate behavior but may also harm self-integrity and fuel negative mindsets about exercise. Our research seeks to devise alternative, more qualitative schemes for encoding personal information. In particular, this paper explores the design of data-driven narratives, given the intuitive and persuasive power of stories. We present WhoIsZuki, a smartphone application that visualizes physical activities and goals as components of a multi-chapter quest, where the main character's progress is tied to the user's. We report on our design process involving online surveys, in-lab studies, and in-the-wild deployments, aimed at refining the interface and the narrative and gaining a deep understanding of people's experiences with this type of feedback. From these insights, we contribute recommendations to guide future development of narrative-based applications for motivating healthy behavior.

Surrogate Decision Making for Children: Who Should Decide?

OBJECTIVE: To identify caregivers' views on preferred surrogate decision makers for their children. STUDY DESIGN: A respondent-anonymous survey was distributed to a convenience sample of adults who accompanied a child to general and subspecialty pediatric care at 2 different institutions or were at the bedside of a child in the pediatric intensive care unit at a third institution in Chicago. RESULTS: We collected 462 valid surveys. The average age of the legal guardian and accompanying child was 36.8 years and 6.6 years, respectively. Most legal guardians designated "other parent with legal authority" as their first choice surrogate decision maker (70%). Respondent's sex, respondent's age, child's age, and child's ethnicity had no effect on first choice surrogate decision maker. "Other parent with legal authority" was less likely to be first choice surrogate if respondents had Medicaid insurance, less than a college degree, or lived in a non-nuclear household (P<.01 for all factors). The surrogacy ladder selected by 31% of legal guardians was "other parent with legal authority," "child's grandparent(s)," and "child's aunt(s) or uncle(s)." No other sequence received more than 10% designation. Study site had no effect on surrogate preference (P = .30). CONCLUSIONS: A surrogacy priority ladder for minors needs to include relatives who are often not included in state surrogacy statutes (eg, grandparents, aunts and uncles). The most popular surrogacy ladder will not be ideal for many families. Parents need to be informed and empowered to choose alternate surrogates, and documented preferences must be easily and widely accessible.

Mindfulness is associated with sleep quality among patients with fibromyalgia.

AIM: Previous studies suggest higher mindfulness may be associated with better sleep quality in people with chronic pain conditions. However, the relationship between mindfulness and sleep in fibromyalgia patients, who commonly suffer from sleep problems, remains unstudied. We examined the relationship between mindfulness and sleep, and how this relationship may be mediated by depression, anxiety, and pain interference in fibromyalgia patients. METHOD: We performed a cross-sectional analysis of baseline data from a randomized trial in fibromyalgia patients. We measured mindfulness (Five Facet Mindfulness Questionnaire), sleep quality and disturbance (Pittsburgh Sleep Quality Index [PSQI], PROMIS Sleep Disturbance [PROMIS-SD]), pain interference (PROMIS Pain Interference), and anxiety and depression (Hospital Anxiety and Depression Scale). Pearson correlations were used to examine associations among mindfulness and sleep quality and disturbance. Mediation analysis was conducted to assess whether pain interference, depression, and anxiety mediated the relationship between mindfulness and sleep. RESULTS: A total of 177 patents with fibromyalgia were included (93% female; mean age 52 ± 12 years; body mass index 30 ± 7 kg/m2 ; 59% White). Higher mindfulness was associated with better sleep quality and less sleep disturbance (PSQI r = -0.23, P = .002; PROMIS-SD r = -.24, P = .002) as well as less pain interference (r = -.31, P < .0001), anxiety (r = -.58, P < .001), and depression (r = -0.54, P < .0001). Pain interference, depression, and anxiety mediated the association between mindfulness and sleep quality and disturbance. CONCLUSION: Higher mindfulness is associated with better sleep in patients with fibromyalgia, with pain interference, depression, and anxiety mediating this relationship. Longitudinal studies are warranted to examine the potential effect of cultivating mindfulness on sleep in fibromyalgia.

Successful deployment of drug-disease interaction clinical decision support across multiple Kaiser Permanente regions.

OBJECTIVE: The study sought to develop a criteria-based scoring tool for assessing drug-disease knowledge base content and creation of a subset and to implement the subset across multiple Kaiser Permanente (KP) regions. MATERIALS AND METHODS: In Phase I, the scoring tool was developed, used to create a drug-disease alert subset, and validated by surveying physicians and pharmacists from KP Northern California. In Phase II, KP enabled the alert subset in July 2015 in silent mode to collect alert firing rates and confirmed that alert burden was adequately reduced. The alert subset was subsequently rolled out to users in KP Northern California. Alert data was collected September 2015 to August 2016 to monitor relevancy and override rates. RESULTS: Drug-disease alert scoring identified 1211 of 4111 contraindicated drug-disease pairs for inclusion in the subset. The survey results showed clinician agreement with subset examples 92.3%-98.5% of the time. Postsurvey adjustments to the subset resulted in KP implementation of 1189 drug-disease alerts. The subset resulted in a decrease in monthly alerts from 32 045 to 1168. Postimplementation monthly physician alert acceptance rates ranged from 20.2% to 29.8%. DISCUSSION: Our study shows that drug-disease alert scoring resulted in an alert subset that generated acceptable interruptive alerts while decreasing overall potential alert burden. Following the initial testing and implementation in its Northern California region, KP successfully implemented the disease interaction subset in 4 regions with additional regions planned. CONCLUSIONS: Our approach could prevent undue alert burden when new alert categories are implemented, circumventing the need for trial live activations of full alert category knowledge bases.

Mindfulness is associated with psychological health and moderates the impact of fibromyalgia.

OBJECTIVE: Previous studies suggest mindfulness is associated with pain and depression. However, its impact in individuals with fibromyalgia remains unclear. We examined associations between mindfulness and physical and psychological symptoms, pain interference, and quality of life in fibromyalgia patients. METHODS: We performed a cross-sectional analysis on baseline data from a fibromyalgia clinical trial. Mindfulness was assessed using the Five Facet Mindfulness Questionnaire (FFMQ). Pearson's correlations and multivariable linear regression models were used to evaluate associations between mindfulness and fibromyalgia impact, pain interference, physical function, depression, anxiety, stress, self-efficacy, and health-related quality of life. We also examined whether mindfulness moderated associations between fibromyalgia impact and psychological outcomes. RESULTS: A total of 177 participants (age 52.0 ± 12.2 (SD) years; 93.2% women; 58.8% white; body mass index 30.1 ± 6.7 kg/m2; FFMQ score 131.3 ± 20.7; Revised Fibromyalgia Impact Questionnaire score 57.0 ± 19.4) were included. Higher total mindfulness was significantly associated with lower fibromyalgia impact (r = - 0.25), pain interference (r = - 0.31), stress (r = - 0.56), anxiety (r = - 0.58), depression (r = - 0.54), and better mental health-related quality of life (r = 0.57). Describing, Acting-with-awareness, and Non-judging facets of mindfulness were also associated with these outcomes. Mindfulness moderated the effect of fibromyalgia impact on anxiety (interaction P = 0.01). CONCLUSION: Higher mindfulness is associated with less pain interference, lower impact of fibromyalgia, and better psychological health and quality of life in people with fibromyalgia. Mindfulness moderates the influence of fibromyalgia impact on anxiety, suggesting mindfulness may alter how patients cope with fibromyalgia. Future studies should assess how mind-body therapies aiming to cultivate mindfulness may impact the well-being of patients with fibromyalgia. KEY POINTS: • Higher mindfulness was associated with better psychological health and lower overall impact of fibromyalgia. • Mindfulness moderated the relationship between overall fibromyalgia impact and anxiety.

Combined Social and Spatial Coding in a Descending Projection from the Prefrontal Cortex.

Social behaviors are crucial to all mammals. Although the prelimbic cortex (PL, part of medial prefrontal cortex) has been implicated in social behavior, it is not clear which neurons are relevant or how they contribute. We found that PL contains anatomically and molecularly distinct subpopulations that target three downstream regions that have been implicated in social behavior: the nucleus accumbens (NAc), amygdala, and ventral tegmental area. Activation of NAc-projecting PL neurons (PL-NAc), but not the other subpopulations, decreased the preference for a social target. To determine what information PL-NAc neurons convey, we selectively recorded from them and found that individual neurons were active during social investigation, but only in specific spatial locations. Spatially specific manipulation of these neurons bidirectionally regulated the formation of a social-spatial association. Thus, the unexpected combination of social and spatial information within the PL-NAc may contribute to social behavior by supporting social-spatial learning.