Designing a Primary Care–Based Deprescribing Intervention for Patients with Dementia and Multiple Chronic Conditions: a Qualitative Study

BackgroundPatients with dementia and multiple chronic conditions (MCC) frequently experience polypharmacy, increasing their risk of adverse drug events.ObjectivesTo elucidate patient, family, and physician perspectives on medication discontinuation and recommended language for deprescribing discussions in order to inform an intervention to increase awareness of deprescribing among individuals with dementia and MCC, family caregivers and primary care physicians. We also explored participant views on culturally competent approaches to deprescribing.DesignQualitative approach based on semi-structured interviews with patients, caregivers, and physicians.ParticipantsPatients aged ≥ 65 years with claims-based diagnosis of dementia, ≥ 1 additional chronic condition, and ≥ 5 chronic medications were recruited from an integrated delivery system in Colorado and an academic medical center in Maryland. We included caregivers when present or if patients were unable to participate due to severe cognitive impairment. Physicians were recruited within the same systems and through snowball sampling, targeting areas with large African American and Hispanic populations.ApproachWe used constant comparison to identify and compare themes between patients, caregivers, and physicians.Key ResultsWe conducted interviews with 17 patients, 16 caregivers, and 16 physicians. All groups said it was important to earn trust before deprescribing, frame deprescribing as routine and positive, align deprescribing with goals of dementia care, and respect caregivers’ expertise. As in other areas of medicine, racial, ethnic, and language concordance was important to patients and caregivers from minority cultural backgrounds. Participants favored direct-to-patient educational materials, support from pharmacists and other team members, and close follow-up during deprescribing. Patients and caregivers favored language that explained deprescribing in terms of altered physiology with aging. Physicians desired communication tips addressing specific clinical situations.ConclusionsCulturally sensitive communication within a trusted patient-physician relationship supplemented by pharmacists, and language tailored to specific clinical situations may support deprescribing in primary care for patients with dementia and MCC.Electronic supplementary materialThe online version of this article (10.1007/s11606-020-06063-y) contains supplementary material, which is available to authorized users.KEY WORDS: deprescribing, patient-physician communication, dementia     

Parental resilience: A neglected construct in resilience research

The substantial focus of resilience research on childhood well‐being has resulted in limited knowledge regarding other aspects of resilience in families, such as that of parents. Informed by literature in childhood and family resilience, in this review, we progress conceptual understanding by focusing on parental resilience. The definition of parental resilience, as the capacity of parents to deliver a competent and quality level of parenting to children despite the presence of risk factors, is offered here as a worthwhile framework through which to explore variables thought to contribute to resilience among parents. A conceptual model is proposed whereby parental psychological well‐being and self‐efficacy, family functioning, and social connectedness are specifically addressed, with each posited as playing an important role in parents’ ability to deliver high‐quality parenting. In addition to these factors, how parents accommodate adversity and find meaning in their everyday lives within their families is hypothesised to be an important process in understanding parental resilience.     

Small bowel sarcoma: A rare case report

Sarcoma of the small bowel is an extremely rare type of small bowel malignancy and represents around 10 per cent of small bowel cancers. Usually asymptomatic, patients can present with chronic abdominal distention with pain and/or weight loss. Most pathologists now refer to small bowel sarcomas (SBS) as gastrointestinal stromal tumours as they are mesenchymal neoplasms believed to be derived from the interstitial cells of Cajal in the gastrointestinal tract. SBS can be highly vascular and commonly ulcerate and/or bleed. They tend to be aggressive and have a poor prognosis. Surgery is the treatment of choice for SBS, with definitive diagnosis usually made postoperatively with the aid of histopathology. We would like to highlight the importance of careful intra-operative examination of an unknown small bowel (SB) mass, which can give the surgeon clues to the type of tumour present. This case report aims to demonstrate this important process: recognising SBS intra-operatively will aid the surgeon with performing the appropriate resection as minute omental metastasis can be present with SBS; in such cases an omentectomy during the laparotomy is recommended. In institutions where available, intra-operative radiotherapy is ideal.     

Test–retest reliability of the unsupported upper-limb exercise test (UULEX) and 6-min peg board ring test (6PBRT) in healthy adult individuals

Background: The unsupported upper-limb exercise (UULEX) and 6-min peg board ring tests (6PBRTs) have been developed to measure peak unsupported arm exercise capacity and arm endurance, respectively, in individuals with chronic obstructive pulmonary disease. These tests are valid and reproducible in this population; however, the reproducibility of healthy adults is currently unknown. Objective: To determine the within-day test–retest reliability of the UULEX and 6PBRT in healthy adults. Method: The study included 41 healthy adults, aged 38.3 ± 17.9 years old, who performed both tests, twice each on the same day, with a 30-min rest in between. Before and immediately after the tests, blood pressure (BP), heart rate (HR), perception of exertion, and arm fatigue were measured. Time to perform the test and number of rings moved were recorded for the UULEX and 6PBRT, respectively. Results: The UULEX was reproducible on Bland–Altman analysis with lower and upper limits of agreement: 2.40 and ?2.49 min, respectively (bias = ?0.05; p = 0.817) and intraclass correlation coefficient (ICC) = 0.85 (p < 0.0001) for time in minutes for the first and second tests. The 6PBRT was not reproducible on Bland–Altman analysis with lower and upper limits of agreement of 31.64 and ?114.54 (bias = ?41.45; p < 0.0001) and ICC = 0.91 (p < 0.0001) for the number of rings moved. Conclusion: UULEX is a reliable test in healthy adults. Only one test is adequate when measuring peak unsupported arm exercise capacity using the UULEX in healthy adults, while more than two tests may be needed to measure arm endurance using the 6PBRT.     

Adverse adipose phenotype and hyperinsulinemia in gravid mice deficient in placental growth factor

Pregnancy-induced metabolic changes are regulated by signals from an expanded adipose organ. Placental growth factor (PlGF), acting through vascular endothelial growth factor receptor-1, may be among those signals. There is a steep rise in circulating PlGF during normal pregnancy, which is repressed in gravidas who develop preeclampsia. PlGF-deficiency in mice impairs adipose vascularization and development. Here we studied young-adult PlGF-deficient (PlGF(-/-)) and wild-type mice on a high-fat diet in the nongravid state and at embryonic day (E) 13.5 or E18.5 of gestation. Litter size and weight were normal, but E18.5 placentas were smaller in PlGF(-/-) pregnancies. PlGF(-/-) mice showed altered intraadipose dynamics, with the following: 1) less blood vessels and fewer brown, uncoupling protein (UCP)-1-positive, adipocytes in white sc and perigonadal fat compartments and 2) white adipocyte hypertrophy. The mRNA expression of beta(3)-adrenergic receptors, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and UCP-1 was decreased accordingly. Moreover, PlGF(-/-) mice showed hyperinsulinemia. Pregnancy-associated changes were largely comparable in PlGF(-/-) and wild-type dams. They included expanded sc fat compartments and adipocyte hypertrophy, whereas adipose expression of key angiogenesis/adipogenesis (vascular endothelial growth factor receptor-1, peroxisome proliferator-activated receptor-gamma(2)) and thermogenesis (beta(3)-adrenergic receptors, peroxisome proliferator-activated receptor-gamma coactivator-1alpha, and UCP-1) genes was down-regulated; circulating insulin levels gradually increased during pregnancy. In conclusion, reduced adipose vascularization in PlGF(-/-) mice impairs adaptive thermogenesis in favor of energy storage, thereby promoting insulin resistance and hyperinsulinemia. Pregnancy adds to these changes by PlGF-independent mechanisms. Disturbed intraadipose dynamics is a novel mechanism to explain metabolic changes in late pregnancy in general and preeclamptic pregnancy in particular.     

Mixed functional characteristics correlating with TCR‐ligand koff‐rate of MHC‐tetramer reactive T cells within the naive T‐cell repertoire

The low frequency of antigen‐specific naïve T cells has challenged numerous laboratories to develop various techniques to study the naïve T‐cell repertoire. Here, we combine the generation of naïve repertoire‐derived antigen‐specific T‐cell lines based on MHC‐tetramer staining and magnetic‐bead enrichment with in‐depth functional assessment of the isolated T cells. Cytomegalovirus (CMV) specific T‐cell lines were generated from seronegative individuals. Generated T‐cell lines consisted of a variety of immunodominant CMV‐epitope‐specific oligoclonal T‐cell populations restricted to various HLA‐molecules (HLA‐A1, A2, B7, B8, and B40), and the functional and structural avidity of the CMV‐specific T cells was studied. Although all CMV‐specific T cells were isolated based on their reactivity toward a specific peptide‐MHC complex, we observed a large variation in the functional avidity of the MHC‐tetramer positive T‐cell populations, which correlated with the structural avidity measured by the recently developed Streptamer k_off‐rate assay. Our data demonstrate that MHC‐tetramer staining is not always predictive for specific T‐cell reactivity, and challenge the sole use of MHC‐tetramers as an indication of the peripheral T‐cell repertoire, independent of the analysis of functional activity or structural avidity parameters.