Durham VA Health Care System

The fact that there is a need for assessing depression, whether as an affect, a symptom, or a disorder is obvious by the numerous scales and inventories available and in use today. The need to assess depression simply and specifically as a psychiatric disorder has not been met by most scales available today. We became acutely aware of this situation in a research project where we needed to correlate both the presence and severity of a depressive disorder in patients with other parameters such as arousal response during sleep and changes with treatment of the depressive disorder. It was felt that the general depression scales used were insufficient for our purpose and that the more specific scales were also inadequate. These inadequacies related to factors such as the length of a scale or inventory being too long and too time consuming, especially for a patient

INTRODUCTION The cerebral cortex underlies our complex cognitive capabilities. Variations in human cortical surface area and thickness are associated with neurological, psychological, and behavioral traits and can be measured in vivo by magnetic resonance imaging (MRI). Studies in model organisms have identified genes that influence cortical structure, but little is known about common genetic variants that affect human cortical structure. RATIONALE To identify genetic variants associated with human cortical structure at both global and regional levels, we conducted a genome-wide association meta-analysis of brain MRI data from 51,665 individuals across 60 cohorts. We analyzed the surface area and average thickness of the whole cortex and 34 cortical regions with known functional specializations. RESULTS We identified 369 nominally genome-wide significant loci ( P < 5 × 10 −8 ) associated with cortical structure in a discovery sample of 33,992 participants of European ancestry. Of the 360 loci for which replication data were available, 241 loci influencing surface area and 66 influencing thickness remained significant after replication, with 237 loci passing multiple testing correction ( P < 8.3 × 10 −10 ; 187 influencing surface area and 50 influencing thickness). Common genetic variants explained 34% (SE = 3%) of the variation in total surface area and 26% (SE = 2%) in average thickness; surface area and thickness showed a negative genetic correlation ( r G = −0.32, SE = 0.05, P = 6.5 × 10 −12 ), which suggests that genetic influences have opposing effects on surface area and thickness. Bioinformatic analyses showed that total surface area is influenced by genetic variants that alter gene regulatory activity in neural progenitor cells during fetal development. By contrast, average thickness is influenced by active regulatory elements in adult brain samples, which may reflect processes that occur after mid-fetal development, such as myelination, branching, or pruning. When considered together, these results support the radial unit hypothesis that different developmental mechanisms promote surface area expansion and increases in thickness. To identify specific genetic influences on individual cortical regions, we controlled for global measures (total surface area or average thickness) in the regional analyses. After multiple testing correction, we identified 175 loci that influence regional surface area and 46 that influence regional thickness. Loci that affect regional surface area cluster near genes involved in the Wnt signaling pathway, which is known to influence areal identity. We observed significant positive genetic correlations and evidence of bidirectional causation of total surface area with both general cognitive functioning and educational attainment. We found additional positive genetic correlations between total surface area and Parkinson’s disease but did not find evidence of causation. Negative genetic correlations were evident between total surface area and insomnia, attention deficit hyperactivity disorder, depressive symptoms, major depressive disorder, and neuroticism. CONCLUSION This large-scale collaborative work enhances our understanding of the genetic architecture of the human cerebral cortex and its regional patterning. The highly polygenic architecture of the cortex suggests that distinct genes are involved in the development of specific cortical areas. Moreover, we find evidence that brain structure is a key phenotype along the causal pathway that leads from genetic variation to differences in general cognitive function. Identifying genetic influences on human cortical structure. ( A ) Measurement of cortical surface area and thickness from MRI. ( B ) Genomic locations of common genetic variants that influence global and regional cortical structure. ( C ) Our results support the radial unit hypothesis that the expansion of cortical surface area is driven by proliferating neural progenitor cells. ( D ) Cortical surface area shows genetic correlation with psychiatric and cognitive traits. Error bars indicate SE. IMAGE CREDITS: (A) K. COURTNEY; (C) M. R. GLASS

BACKGROUND: For chronically ill patients, readmission to the hospital can be frequent and costly. We studied the effect of an intervention designed to increase access to primary care after discharge from the hospital, with the goals of reducing readmissions and emergency department visits and increasing patients' quality of life and satisfaction with care. METHODS: In a multicenter randomized, controlled trial at nine Veterans Affairs Medical Centers, we randomly assigned 1396 veterans hospitalized with diabetes, chronic obstructive pulmonary disease, or congestive heart failure to receive either usual care or an intensive primary care intervention. The intervention involved close follow-up by a nurse and a primary care physician, beginning before discharge and continuing for the next six months. RESULTS: The patients were severely ill. Half of those with congestive heart failure (504 patients) had disease in New York Heart Association class III or IV; 30 percent of those with diabetes (751 patients) had end-organ damage; and a quarter of those with chronic obstructive pulmonary disease (583 patients) required home oxygen treatment or oral corticosteroids. The patients had extremely poor quality-of-life scores. Although they received more intensive primary care than the controls, the patients in the intervention group had significantly higher rates of readmission (0.19 vs 0.14 per month, P = 0.005) and more days of rehospitalization (10.2 vs 8.8, P = 0.041). The patients in the intervention group were more satisfied with their care (P < 0.001), but there was no difference between the study groups in quality-of-life scores, which remained very low (P = 0.53). CONCLUSIONS: For veterans discharged from Veterans Affairs hospitals, the primary care intervention we studied increased rather than decreased the rate of rehospitalization, although patients in the intervention group were more satisfied with their care.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations.

BACKGROUND: Qualitative approaches, alone or in mixed methods, are prominent within implementation science. However, traditional qualitative approaches are resource intensive, which has led to the development of rapid qualitative approaches. Published rapid approaches are often inductive in nature and rely on transcripts of interviews. We describe a deductive rapid analysis approach using the Consolidated Framework for Implementation Research (CFIR) that uses notes and audio recordings. This paper compares our rapid versus traditional deductive CFIR approach. METHODS: Semi-structured interviews were conducted for two cohorts of the Veterans Health Administration (VHA) Diffusion of Excellence (DoE). The CFIR guided data collection and analysis. In cohort A, we used our traditional CFIR-based deductive analysis approach (directed content analysis), where two analysts completed independent in-depth manual coding of interview transcripts using qualitative software. In cohort B, we used our new rapid CFIR-based deductive analysis approach (directed content analysis), where the primary analyst wrote detailed notes during interviews and immediately "coded" notes into a MS Excel CFIR construct by facility matrix; a secondary analyst then listened to audio recordings and edited the matrix. We tracked time for our traditional and rapid deductive CFIR approaches using a spreadsheet and captured transcription costs from invoices. We retrospectively compared our approaches in terms of effectiveness and rigor. RESULTS: Cohorts A and B were similar in terms of the amount of data collected. However, our rapid deductive CFIR approach required 409.5 analyst hours compared to 683 h during the traditional deductive CFIR approach. The rapid deductive approach eliminated $7250 in transcription costs. The facility-level analysis phase provided the greatest savings: 14 h/facility for the traditional analysis versus 3.92 h/facility for the rapid analysis. Data interpretation required the same number of hours for both approaches. CONCLUSION: Our rapid deductive CFIR approach was less time intensive and eliminated transcription costs, yet effective in meeting evaluation objectives and establishing rigor. Researchers should consider the following when employing our approach: (1) team expertise in the CFIR and qualitative methods, (2) level of detail needed to meet project aims, (3) mode of data to analyze, and (4) advantages and disadvantages of using the CFIR.

BACKGROUND: Self-monitoring of blood pressure (BP) appears to reduce BP in hypertension but important questions remain regarding effective implementation and which groups may benefit most. This individual patient data (IPD) meta-analysis was performed to better understand the effectiveness of BP self-monitoring to lower BP and control hypertension. METHODS AND FINDINGS: Medline, Embase, and the Cochrane Library were searched for randomised trials comparing self-monitoring to no self-monitoring in hypertensive patients (June 2016). Two reviewers independently assessed articles for eligibility and the authors of eligible trials were approached requesting IPD. Of 2,846 articles in the initial search, 36 were eligible. IPD were provided from 25 trials, including 1 unpublished study. Data for the primary outcomes-change in mean clinic or ambulatory BP and proportion controlled below target at 12 months-were available from 15/19 possible studies (7,138/8,292 [86%] of randomised participants). Overall, self-monitoring was associated with reduced clinic systolic blood pressure (sBP) compared to usual care at 12 months (-3.2 mmHg, [95% CI -4.9, -1.6 mmHg]). However, this effect was strongly influenced by the intensity of co-intervention ranging from no effect with self-monitoring alone (-1.0 mmHg [-3.3, 1.2]), to a 6.1 mmHg (-9.0, -3.2) reduction when monitoring was combined with intensive support. Self-monitoring was most effective in those with fewer antihypertensive medications and higher baseline sBP up to 170 mmHg. No differences in efficacy were seen by sex or by most comorbidities. Ambulatory BP data at 12 months were available from 4 trials (1,478 patients), which assessed self-monitoring with little or no co-intervention. There was no association between self-monitoring and either lower clinic or ambulatory sBP in this group (clinic -0.2 mmHg [-2.2, 1.8]; ambulatory 1.1 mmHg [-0.3, 2.5]). Results for diastolic blood pressure (dBP) were similar. The main limitation of this work was that significant heterogeneity remained. This was at least in part due to different inclusion criteria, self-monitoring regimes, and target BPs in included studies. CONCLUSIONS: Self-monitoring alone is not associated with lower BP or better control, but in conjunction with co-interventions (including systematic medication titration by doctors, pharmacists, or patients; education; or lifestyle counselling) leads to clinically significant BP reduction which persists for at least 12 months. The implementation of self-monitoring in hypertension should be accompanied by such co-interventions.

The most common reported reasons for intensive care unit admission for patients with severe coronavirus disease 2019 (COVID-19) are either hypoxemic respiratory failure leading to mechanical ventilation or hypotension requiring vasopressor support. Data on AKI are either lacking1 or only reporting incidence on the basis of case series and retrospective studies.2 In this Perspective, we emphasize that AKI can be a severe complication of COVID-19 and highlight the importance of assessing, defining, and reporting the course of AKI. Understandably relevant information that normally would be part of clinical descriptions and research publications has not been collected because of the magnitude and accelerated pace of the COVID-19 pandemic. Of great relevance is a preprint in medRxiv reporting a 23% AKI incidence among 85 patients (over 60% in high-risk patients). The authors analyzed kidney histology from autopsies of six patients who had AKI showing severe acute tubular necrosis with lymphocyte and macrophage infiltration, but it is not clear from this report if these patients had actually developed cortical necrosis (B. Diao, C.H. Wang, R.S. Wang, Z.Q. Feng, Y.J. Tan, H.M. Wang, et al.: Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection [preprint posted online April 10, 2020]. medRxivdoi:10.1101/2020.03.04.20031120). An important report on autopsy findings from deceased patients with COVID-19 again demonstrated prominent acute proximal tubular injury, but also peritubular erythrocyte aggregation and glomerular fibrin thrombi with ischemic collapse.3 This paper also reported endothelial damage, hemosiderin deposition, pigment casts related to rhabdomyolysis, and inflammation. Notably, some of these patients lacked evidence of AKI as detected by routine measures (creatinine and/or BUN), highlighting the possibility of substantial subclinical kidney injury. Recent clinical and autopsy reports of COVID-19 from China and the United States confirm increased clotting and disseminated intravascular coagulation with small vessel thrombosis and pulmonary infarction.4 Further, elevated d-dimer and low platelet levels correlated with worse outcomes.4 We are aware that some patients with COVID-19 manifest evidence of microangiopathy in other organ systems, such as splenic infarction or presenting symptoms of loin pain and hematuria suggesting renal infarction. Numerous observations by treating physicians attest that there is increased occurrence of circuit clotting in patients with COVID-19 undergoing dialysis. COVID-19 is also associated with increased myocardial injury that mimics myocardial infarction, possibly from myocarditis and microangiopathy.5 Thus, it is conceivable that the hypercoagulable state that appears to be a characteristic complication of severe COVID-19 could, in some cases, foster the evolution of acute tubular necrosis to cortical necrosis and, therefore, irreversible kidney failure. Innate immunity and coagulation pathways are intricately linked.6 COVID-19–associated macrophage activation, hyperferritinemia, cytokine storm, and release of pathogen-associated molecular patterns and damage-associated molecular proteins can result in release of tissue factor and activation of coagulation factors that create a predisposition to hypercoagulability.6 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may also target lymphocytes as they express angiotensin-converting enzyme 2 (ACE2), leading to lymphocyte activation and, consequently, activation-induced cell death than can result in lymphopenia of both CD4+ and CD8+ T cells.7 Further, procoagulation pathways and complement systems can activate each other. In support of this interaction in COVID-19, Diao and colleagues (B. Diao, C.H. Wang, R.S. Wang, Z.Q. Feng, Y.J. Tan, H.M. Wang, et al.: Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection [preprint posted online April 10, 2020]. medRxivdoi:10.1101/2020.03.04.20031120) observed strong complement C5b-9 (membrane attack complex) deposition in renal tubules of six patients with SARS-CoV-2 infection, suggesting activation of the complement pathway. An interaction between angiotensin II (AngII) overactivity, innate/adaptive immune and complement pathways, and the coagulation system could influence AKI severity and outcomes. Inflammation-induced erythrocyte aggregation (reflected as elevated erythrocyte sedimentation rate) and heme-mediated pathology may worsen oxidative stress, inflammation, and complement activation, to aggravate microvascular injury.8 Further, organ crosstalk between the injured lung, the heart, and the kidney can worsen pathology. Detailed studies to decipher the nature of coagulation dysfunction, microangiopathy, and potential role for innate immune and complement pathways are required to gain further insights regarding kidney pathology in COVID-19. Also of interest is the finding that SARS-CoV-2 nucleocapsid protein was observed in tubular structures in the kidneys from the six patients examined, and nucleocapsid protein–positive inclusion bodies were also observed in the cytoplasm (B. Diao, C.H. Wang, R.S. Wang, Z.Q. Feng, Y.J. Tan, H.M. Wang, et al.: Human kidney is a target for novel severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2] infection [preprint posted online April 10, 2020]. medRxivdoi:10.1101/2020.03.04.20031120). Su et al.3 similarly observed the presence of virus-like particles in podocytes and renal tubular epithelial cells by electron microscopy, and SARS-CoV-2 nucleoprotein antibody stained renal tubular epithelia positive, but the specificity of the antibody used needs to be established. Although, as far as we know, SARS-CoV-2 RNA, has not been detected in the kidney, these results indicate that SARS-CoV-2 could directly infect human kidney tubules and induce cytoplasmic renal tubular inclusions, a feature observed in other virus-associated nephropathies. Thus, although AKI may be attributable to hypotension and decreased kidney perfusion secondary to hemodynamic or hemostatic factors or associated sepsis, one needs to consider that viral infection of the kidneys with viral replication directly in kidney parenchyma also plays a role. The main binding site for SARS-CoV-2, like SARS-CoV, is the ACE2 protein, which is expressed in the kidney much more than the lungs.9,10 ACE2 is expressed on the brush border apical membrane of the proximal tubule, where it colocalizes with angiotensin-converting enzyme (ACE), and is also present at lower levels in podocytes.10 It is conceivable that the virus could enter the kidney by invading podocytes first, and thus gain access to the tubular fluid and subsequently bind to ACE2 in the proximal tubule. In primary human airway epithelia, ACE2 is expressed apically, and SARS-CoV-2 infection predominantly occurs on the apical surface, but infection can occur on the basolateral surface at low efficiency.11 Coronavirus entry into host target cells also requires fusion of the viral envelope with cellular membranes. Fusion-activated SARS-CoV peptides are created by specific proteolytic cleavage of the S proteins, in a step called “priming.” As a consequence, cell infectivity not only depends on ACE2 expression, but is also governed by types of proteases found in a given cell type. In the kidney, Transmembrane protease, serine 2 (TMPRSS2)12–1314 (Figure 1), which primes the SARS-CoV-2 S protein, is robustly expressed in the distal nephron rather than the proximal tubule. It remains to be determined if other TMPRSS in the proximal tubule can mediate the priming step, such as TMPRSS 4, 5, or 9. Alternatively, tropism of SARS-CoV-2 might be expanded by the unique furin cleavage site in the Spike protein that is processed during biogenesis.14Figure 1.: Single-cell RNA of SARS-COV-2 receptor (ACE2) and known priming proteases in the kidney. There is no clear correspondence in single-cell RNA between ACE2 and TMPRSS2. EC, endothelial cell; PT, proximal tubule (S1, Segment one; S2 Segment two, S3 Segment three); LH(DL), loop of henle(descending thin limb); LH(AL), loop of henle(descending limb type one [#type 1] and type two [type #2]); DCT, distal convoluted tubule; CNT, connecting tubule; PC, principal cell; IC-A, alpha intercalated cell; IC-B, beta intercalated cell; pct. exp, percentexpressed. Data were extracted with permission from human kidney single-cell RNA-sequencing data.12 , 13Any effect of proteinuria, hyperinflammation, or tubular injury on proximal tubular ACE2 expression or SARS-CoV-2 viral entry is currently unknown. Viral replication in podocytes and the ensuing damage could in theory account for the proteinuria that has been reported in patients with COVID-19.2 Further, COVID-19–associated hemophagocytic macrophage activation and microangiopathy could also cause AKI and podocyte damage. Of interest, cases of COVID-19–associated collapsing glomerulopathy have been described.15 Regardless of direct viral infection of the kidney, AngII is likely increased in the context of acute lung injury16 and there is evidence that ACE2 is downregulated in AKI. This may lead to type 1 angiotensin receptor activation as well as decreased angiotensin (1–7) formation and subsequent worsening of AKI. This is particularly important in subpopulations of patients who have CKD, especially those with diabetic kidney disease (DKD). ACE2 and ACE mRNA and protein expression are altered in mouse models of DKD and in patients with DKD.10,17 Thus, patients with CKD, especially those with DKD, who develop COVID-19 may be at higher risk of AKI because of baseline upregulation of the ACE and downregulation of ACE2, a combination that primes a proinflammatory (including complement activation) and profibrotic state in the kidneys. Interestingly, a recent study described single-cell transcriptome analysis in 15 normal human kidney samples.18 In this study, the proportions of kidney cells expressing ACE2, the SARS-CoV-2 binding site, and proteases of the TMPRSS family were compared between occidental and Asian individuals.18 Interestingly, the expression of ACE2 and kidney disease–related genes was higher in occidental donors relative to Asian donors. This would suggest that the susceptibility to kidney injury from coronavirus infection might be higher in individuals of occidental rather than Asian descent. We are not aware, however, of data supporting this possibility. Despite the very limited information on kidney involvement in COVID-19, AKI appears to involve a complex process driven by virus-mediated injury, cytokine storm, AngII pathway activation, dysregulation of complement, hypercoagulation, and microangiopathy interacting with common and known risk factors for AKI (Figure 2). There is paucity of data regarding clinical and laboratory characteristics of AKI in patients with COVID-19. We urge that further studies describing and analyzing the clinical course of patients with COVID-19 include appropriate indices of kidney function and diagnosis of AKI in their analyses, including kidney injury markers, urine microscopy, quantified urine protein, urine output, and urine electrolytes. Markers of macrophage activation, coagulation, microangiopathy, and complement activation, as well as kidney imaging and need for KRT (with relevant details), are important data needed to further our understanding of AKI pathophysiology associated with COVID-19. Rates of reversibility of, or partial improvement in, kidney function and any kidney biopsy results (including immunofluorescence and electron microscopy) should be reported. In the rush to report medical complications of COVID-19, we are missing valuable clinical information. Speculation about specific interventions would not be appropriate until we obtain appropriate information. We advocate for a complete and standardized appraisal of the clinical and laboratory picture so that preventative and therapeutic strategies for AKI can be appropriately designed and implemented.Figure 2.: Targeting of ACE2 by SARS-CoV-2 results in angiotensin dysregulation, innate and adaptive immune pathway activation, and hypercoagulation to result in organ injury and AKI associated with COVID-19. Organ crosstalk between the injured lungs, the heart, and the kidney may further propagate injury. CD8+ T-cells and natural killer cells can restrain macrophage activation and are potential targets for SARS-CoV-2. Ang 1–7, angiotensin 1–7; ATN, acute tubular necrosis. ACE2, angiotensin converting enzyme 2; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2; TMPRSS2, transmembrane protease, serine 2.Disclosures Dr. Batlle reports nonfinancial support from Angiotensin Therapeutics Inc., outside the submitted work. In addition, Dr. Batlle has a patent “Active low molecular weight variants of angiotensin converting enzyme 2” issued. Dr. Hiremath reports other from University of Ottawa, Department of Medicine, outside the submitted work. Dr. Soler reports personal fees from AstraZeneca, nonfinancial support from Boehringer, nonfinancial support from Eli Lilly, nonfinancial support from Esteve, personal fees from Janssen, personal fees from Novo Nordisk, outside the submitted work. Dr. South reports other from National Institutes of Health, National Heart, Lung, and Blood Institute, and Loan Repayment Programs, during the conduct of the study. All remaining authors have nothing to disclose. Funding Dr. Batlle reports grants from National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), during the conduct of the study. Dr. Swaminathan reports grants from NIDDK, during the conduct of the study. Dr. South reports grants from National Heart, Lung, and Blood Institute and NIDDK, during the conduct of the study. Dr. Welling reports grants from NIDDK and the Foudation LeDucq.

BACKGROUND: Responsible, shared decision making on the part of physicians and patients about the potential use of cardiopulmonary resuscitation (CPR) requires patients who are educated about the procedure's risks and benefits. Television is an important source of information about CPR for patients. We analyzed how three popular television programs depict CPR. METHODS: We watched all the episodes of the television programs ER and Chicago Hope during the 1994-1995 viewing season and 50 consecutive episodes of Rescue 911 broadcast over a three-month period in 1995. We identified all occurrences of CPR in each episode and recorded the causes of cardiac arrest, the identifiable demographic characteristics of the patients, the underlying illnesses, and the outcomes. RESULTS: There were 60 occurrences of CPR in the 97 television episodes--31 on ER, 11 on Chicago Hope, and 18 on Rescue 911. In the majority of cases, cardiac arrest was caused by trauma; only 28 percent were due to primary cardiac causes. Sixty-five percent of the cardiac arrests occurred in children, teenagers, or young adults. Seventy-five percent of the patients survived the immediate arrest, and 67 percent appeared to have survived to hospital discharge. CONCLUSIONS: The survival rates in our study are significantly higher than the most optimistic survival rates in the medical literature, and the portrayal of CPR on television may lead the viewing public to have an unrealistic impression of CPR and its chances for success. Physicians discussing the use of CPR with patients and families should be aware of the images of CPR depicted on television and the misperceptions these images may foster.

Common ground on dietary approaches for the prevention, management, and potential remission of type 2 diabetes can be found, argue Nita G Forouhi and colleagues Dietary factors are of paramount importance in the management and prevention of type 2 diabetes. Despite progress in formulating evidence based dietary guidance, controversy and confusion remain. In this article, we examine the evidence for areas of consensus as well as ongoing uncertainty or controversy about dietary guidelines for type 2 diabetes. What is the best dietary approach? Is it possible to achieve remission of type 2 diabetes with lifestyle behaviour changes or is it inevitably a condition causing progressive health decline? We also examine the influence of nutrition transition and population specific factors in the global context and discuss future directions for effective dietary and nutritional approaches to manage type 2 diabetes and their implementation.

Importance: Despite growing evidence, the role of spirituality in serious illness and health has not been systematically assessed. Objective: To review evidence concerning spirituality in serious illness and health and to identify implications for patient care and health outcomes. Evidence Review: Searches of PubMed, PsycINFO, and Web of Science identified articles with evidence addressing spirituality in serious illness or health, published January 2000 to April 2022. Independent reviewers screened, summarized, and graded articles that met eligibility criteria. Eligible serious illness studies included 100 or more participants; were prospective cohort studies, cross-sectional descriptive studies, meta-analyses, or randomized clinical trials; and included validated spirituality measures. Eligible health outcome studies prospectively examined associations with spirituality as cohort studies, case-control studies, or meta-analyses with samples of at least 1000 or were randomized trials with samples of at least 100 and used validated spirituality measures. Applying Cochrane criteria, studies were graded as having low, moderate, serious, or critical risk of bias, and studies with serious and critical risk of bias were excluded. Multidisciplinary Delphi panels consisting of clinicians, public health personnel, researchers, health systems leaders, and medical ethicists qualitatively synthesized and assessed the evidence and offered implications for health care. Evidence-synthesis statements and implications were derived from panelists' qualitative input; panelists rated the former on a 9-point scale (from "inconclusive" to "strongest evidence") and ranked the latter by order of priority. Findings: Of 8946 articles identified, 371 articles met inclusion criteria for serious illness; of these, 76.9% had low to moderate risk of bias. The Delphi panel review yielded 8 evidence statements supported by evidence categorized as strong and proposed 3 top-ranked implications of this evidence for serious illness: (1) incorporate spiritual care into care for patients with serious illness; (2) incorporate spiritual care education into training of interdisciplinary teams caring for persons with serious illness; and (3) include specialty practitioners of spiritual care in care of patients with serious illness. Of 6485 health outcomes articles, 215 met inclusion criteria; of these, 66.0% had low to moderate risk of bias. The Delphi panel review yielded 8 evidence statements supported by evidence categorized as strong and proposed 3 top-ranked implications of this evidence for health outcomes: (1) incorporate patient-centered and evidence-based approaches regarding associations of spiritual community with improved patient and population health outcomes; (2) increase awareness among health professionals of evidence for protective health associations of spiritual community; and (3) recognize spirituality as a social factor associated with health in research, community assessments, and program implementation. Conclusions and Relevance: This systematic review, analysis, and process, based on highest-quality evidence available and expert consensus, provided suggested implications for addressing spirituality in serious illness and health outcomes as part of person-centered, value-sensitive care.

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal

BACKGROUND: Resilience has been described in the psychosocial literature as the capacity to maintain or regain well-being during or after adversity. Physical resilience is a newer concept that is highly relevant to successful aging. Our objective was to characterize the emerging construct of resilience as it pertains to physical health in older adults, and to identify gaps and opportunities to advance research in this area. METHODS: We conducted a systematic review to identify English language papers published through January 2015 that apply the term "resilience" in relation to physical health in older adults. We applied a modified framework analysis to characterize themes in implicit or explicit definitions of physical resilience. RESULTS: Of 1,078 abstracts identified, 49 articles met criteria for inclusion. Sixteen were letters or concept papers, and only one was an intervention study. Definitions of physical resilience spanned cellular to whole-person levels, incorporated many outcome measures, and represented three conceptual themes: resilience as a trait, trajectory, or characteristic/capacity. CONCLUSIONS: Current biomedical literature lacks consensus on how to define and measure physical resilience. We propose a working definition of physical resilience at the whole person level: a characteristic which determines one's ability to resist or recover from functional decline following health stressor(s). We present a conceptual framework that encompasses the related construct of physiologic reserve. We discuss gaps and opportunities in measurement, interactions across contributors to physical resilience, and points of intervention.

BACKGROUND: Daily step counts is an intuitive metric that has demonstrated success in motivating physical activity in adults and may hold potential for future public health physical activity recommendations. This review seeks to clarify the pattern of the associations between daily steps and subsequent all-cause mortality, cardiovascular disease (CVD) morbidity and mortality, and dysglycemia, as well as the number of daily steps needed for health outcomes. METHODS: A systematic review was conducted to identify prospective studies assessing daily step count measured by pedometer or accelerometer and their associations with all-cause mortality, CVD morbidity or mortality, and dysglycemia (dysglycemia or diabetes incidence, insulin sensitivity, fasting glucose, HbA1c). The search was performed across the Medline, Embase, CINAHL, and the Cochrane Library databases from inception to August 1, 2019. Eligibility criteria included longitudinal design with health outcomes assessed at baseline and subsequent timepoints; defining steps per day as the exposure; reporting all-cause mortality, CVD morbidity or mortality, and/or dysglycemia outcomes; adults ≥18 years old; and non-patient populations. RESULTS: Seventeen prospective studies involving over 30,000 adults were identified. Five studies reported on all-cause mortality (follow-up time 4-10 years), four on cardiovascular risk or events (6 months to 6 years), and eight on dysglycemia outcomes (3 months to 5 years). For each 1000 daily step count increase at baseline, risk reductions in all-cause mortality (6-36%) and CVD (5-21%) at follow-up were estimated across a subsample of included studies. There was no evidence of significant interaction by age, sex, health conditions or behaviors (e.g., alcohol use, smoking status, diet) among studies that tested for interactions. Studies examining dysglycemia outcomes report inconsistent findings, partially due to heterogeneity across studies of glycemia-related biomarker outcomes, analytic approaches, and sample characteristics. CONCLUSIONS: Evidence from longitudinal data consistently demonstrated that walking an additional 1000 steps per day can help lower the risk of all-cause mortality, and CVD morbidity and mortality in adults, and that health benefits are present below 10,000 steps per day. However, the shape of the dose-response relation is not yet clear. Data are currently lacking to identify a specific minimum threshold of daily step counts needed to obtain overall health benefit.

Research on assessing or managing medication adherence applies approaches from observational, interventional, and implementation science that spans many disciplines and demands coherent conceptualization, valid methods, appropriate analyses, and complete and accurate reporting. To ensure such reporting, the European Society for Patient Adherence, COMpliance, and Persistence (ESPACOMP) Medication Adherence Reporting Guideline (EMERGE) recommends standard reporting approaches based on an accepted taxonomy. This guideline is derived from a literature review, a reactive Delphi study with 26 medication adherence experts from many countries and disciplines, and feedback from ESPACOMP members. It is designed to supplement existing guidelines for health research reporting and is structured around 4 minimum reporting criteria and 17 items reflecting best reporting practice. By enhancing and harmonizing research reporting, EMERGE aims to advance research and, ultimately, patient outcomes.

OBJECTIVES: To find and validate generalizable sepsis subtypes using data-driven clustering. DESIGN: We used advanced informatics techniques to pool data from 14 bacterial sepsis transcriptomic datasets from eight different countries (n = 700). SETTING: Retrospective analysis. SUBJECTS: Persons admitted to the hospital with bacterial sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A unified clustering analysis across 14 discovery datasets revealed three subtypes, which, based on functional analysis, we termed "Inflammopathic, Adaptive, and Coagulopathic." We then validated these subtypes in nine independent datasets from five different countries (n = 600). In both discovery and validation data, the Adaptive subtype is associated with a lower clinical severity and lower mortality rate, and the Coagulopathic subtype is associated with higher mortality and clinical coagulopathy. Further, these clusters are statistically associated with clusters derived by others in independent single sepsis cohorts. CONCLUSIONS: The three sepsis subtypes may represent a unifying framework for understanding the molecular heterogeneity of the sepsis syndrome. Further study could potentially enable a precision medicine approach of matching novel immunomodulatory therapies with septic patients most likely to benefit.

Spirituality is an important part of African-American culture and is often cited as an explanation for the more-aggressive treatment preferences of some African Americans at the end of life. This paper reviews the literature on spiritual beliefs that may influence the treatment decisions of African Americans. Medline 1966 to February 2003, Psych Info 1872 to February 2003, and CINAHL 1982 to February 2003 were searched for studies exploring spiritual beliefs that may influence the treatment preferences of African Americans. All candidate papers were examined for quality, and data were extracted on study population, design, analysis, and results to identify recurrent themes. Forty studies met inclusion criteria. Recurrent themes describing spiritual beliefs that may influence the treatment preferences of African Americans throughout the course of illness include the following: spiritual beliefs and practices are a source of comfort, coping, and support and are the most effective way to influence healing; God is responsible for physical and spiritual health; and the doctor is God's instrument. Spiritual beliefs specifically addressing treatment preferences at the end of life include: only God has power to decide life and death, there are religious prohibitions against physician-assisted death or advance directives limiting life-sustaining treatments, and divine intervention and miracles occur. For some African Americans, spiritual beliefs are important in understanding and coping with illness and may provide a framework within which treatment decisions are made. Given the growing ethnic diversity of the United States, some understanding of the complexities of culture and spirituality is essential for healthcare providers.

CONTEXT: Patients with limited literacy are at higher risk for poor health outcomes; however, physicians' perceptions are inaccurate for identifying these patients. OBJECTIVE: To systematically review the accuracy of brief instruments for identifying patients with limited literacy. DATA SOURCES: Search of the English-language literature from 1969 through February 2010 using PubMed, Psychinfo, and bibliographies of selected manuscripts for articles on health literacy, numeracy, reading ability, and reading skill. STUDY SELECTION: Prospective studies including adult patients 18 years or older that evaluated a brief instrument for identifying limited literacy in a health care setting compared with an accepted literacy reference standard. DATA EXTRACTION: Studies were evaluated independently by 2 reviewers who each abstracted information and assigned an overall quality rating. Disagreements were adjudicated by a third reviewer. DATA SYNTHESIS: Ten studies using 6 different instruments met inclusion criteria. Among multi-item measures, the Newest Vital Sign (English) performed moderately well for identifying limited literacy based on 3 studies. Among the single-item questions, asking about a patient's use of a surrogate reader, confidence filling out medical forms, and self-rated reading ability performed moderately well in identifying patients with inadequate or marginal literacy. Asking a patient, "How confident are you in filling out medical forms by yourself?" is associated with a summary likelihood ratio (LR) for limited literacy of 5.0 (95% confidence interval [CI], 3.8-6.4) for an answer of "a little confident" or "not at all confident"; a summary LR of 2.2 (95% CI, 1.5-3.3) for "somewhat confident"; and a summary LR of 0.44 (95% CI, 0.24-0.82) for "quite a bit" or "extremely confident." CONCLUSION: Several single-item questions, including use of a surrogate reader and confidence with medical forms, were moderately effective for quickly identifying patients with limited literacy.

BACKGROUND: Patients with prostate cancer who have high-risk biochemical recurrence have an increased risk of progression. The efficacy and safety of enzalutamide plus androgen-deprivation therapy and enzalutamide monotherapy, as compared with androgen-deprivation therapy alone, are unknown. METHODS: In this phase 3 trial, we enrolled patients with prostate cancer who had high-risk biochemical recurrence with a prostate-specific antigen doubling time of 9 months or less. Patients were randomly assigned, in a 1:1:1 ratio, to receive enzalutamide (160 mg) daily plus leuprolide every 12 weeks (combination group), placebo plus leuprolide (leuprolide-alone group), or enzalutamide monotherapy (monotherapy group). The primary end point was metastasis-free survival, as assessed by blinded independent central review, in the combination group as compared with the leuprolide-alone group. A key secondary end point was metastasis-free survival in the monotherapy group as compared with the leuprolide-alone group. Other secondary end points were patient-reported outcomes and safety. RESULTS: A total of 1068 patients underwent randomization: 355 were assigned to the combination group, 358 to the leuprolide-alone group, and 355 to the monotherapy group. The patients were followed for a median of 60.7 months. At 5 years, metastasis-free survival was 87.3% (95% confidence interval [CI], 83.0 to 90.6) in the combination group, 71.4% (95% CI, 65.7 to 76.3) in the leuprolide-alone group, and 80.0% (95% CI, 75.0 to 84.1) in the monotherapy group. With respect to metastasis-free survival, enzalutamide plus leuprolide was superior to leuprolide alone (hazard ratio for metastasis or death, 0.42; 95% CI, 0.30 to 0.61; P<0.001); enzalutamide monotherapy was also superior to leuprolide alone (hazard ratio for metastasis or death, 0.63; 95% CI, 0.46 to 0.87; P = 0.005). No new safety signals were observed, with no substantial between-group differences in quality-of-life measures. CONCLUSIONS: In patients with prostate cancer with high-risk biochemical recurrence, enzalutamide plus leuprolide was superior to leuprolide alone with respect to metastasis-free survival; enzalutamide monotherapy was also superior to leuprolide alone. The safety profile of enzalutamide was consistent with that shown in previous clinical studies, with no apparent detrimental effect on quality of life. (Funded by Pfizer and Astellas Pharma; EMBARK ClinicalTrials.gov number, NCT02319837.).

BACKGROUND: Rapid approaches to collecting and analyzing qualitative interview data can accelerate discovery timelines and intervention development while maintaining scientific rigor. We describe the application of these methods to a program designed to improve care coordination between the Veterans Health Administration (VHA) and community providers. METHODS: Care coordination between VHA and community providers can be challenging in rural areas. The Telehealth-based Coordination of Non-VHA Care (TECNO Care) intervention was designed to improve care coordination among VHA and community providers. To ensure contextually appropriate implementation of TECNO Care, we conducted preimplementation interviews with veterans, VHA administrators, and VHA and community providers involved in community care. Using both a rapid approach and qualitative analysis, an interviewer and 1-2 note-taker(s) conducted interviews. RESULTS: Over 5 months, 18 stakeholders were interviewed and we analyzed these data to identify how best to deliver TECNO Care. Responses relevant to improving care coordination include health system characteristics; target population; metrics and outcomes; challenges with the current system; and core components. Veterans who frequently visit VHA or community providers and are referred for additional services are at risk for poor outcomes and may benefit from additional care coordination. Using these data, we designed TECNO Care to include information on VHA services and processes, assist in the timely completion of referrals, and facilitate record sharing. CONCLUSION: Rapid qualitative analysis can inform near real-time intervention development and ensure relevant content creation while setting the stage for stakeholder buy-in. Rigorous and timely analyses support the delivery of contextually appropriate, efficient, high-value patient care.