Combined Effects of Depression and Chronic Disease on the Risk of Mortality: The Korean Longitudinal Study of Aging (2006-2016).

BACKGROUND: The prevalence of depression is much higher in people with chronic disease than in the general population. Depression exacerbates existing physical conditions, resulting in a higher-than-expected death rate from the physical condition itself. In our aging society, the prevalence of multimorbid patients is expected to increase; the resulting mental problems, especially depression, should be considered. Using a large-scale cohort from the Korean Longitudinal Study of Aging (KLoSA), we analyzed the combined effects of depression and chronic disease on all-cause mortality. METHODS: We analyzed 10-year (2006-2016) longitudinal data of 9,819 individuals who took part in the KLoSA, a nationwide survey of people aged 45-79 years. We examined the association between multimorbidity and depression using chi-square test and logistic regression. We used the Cox proportional hazard model to determine the combined effects of multimorbidity and depression on the all-cause mortality risk. RESULTS: During the 10-year follow up, 1,574 people (16.0%) died. The hazard ratio associated with mild depression increased from 1.35 (95% confidence interval [CI], 1.05-1.73) for no chronic disease to 1.25 (95% CI, 0.98-1.60) for 1 chronic disease, and to 2.00 (95% CI, 1.58-2.52) for multimorbidity. The hazard ratio associated with severe depression increased from 1.73 (95% CI, 1.33-2.24) for no chronic disease, to 2.03 (95% CI, 1.60-2.57) for 1 chronic disease, and to 2.94 (95% CI, 2.37-3.65) for multimorbidity. CONCLUSION: Patients with coexisting multimorbidity and depression are at an increased risk of all-cause mortality than those with chronic disease or depression alone.

A Pharmaceutical Dispensing-based Index of Mortality Risk From Long-term Conditions Performed as well as Hospital Record-based Indices.

OBJECTIVE: The objective of this study was to develop and validate a mortality risk index from multimorbidity using pharmaceutical dispensing data. DESIGN: The P3 (Pharmaceutical Prescribing Profile) mortality risk index was created (development n=2,331,645) using pharmaceutical dispensing records for the last 12 months for long-term conditions. ß coefficients from a Cox proportional hazards model for mortality provided component scores for 30 medication categories. Index validity was tested (validation n=1,000,166) for risk of mortality and overnight hospitalization over 1 year, and predictive ability calculated for the P3 index relative to the hospital admission-based Charlson and M3 indices (all models adjusted for age/sex). SETTING: This study was carried out in the setting of routine health data sources for the New Zealand adult general population, for an index date of January 1, 2012. RESULTS: The P3 index performed equivalently to Charlson for 1-year mortality risk [c-statistics=0.920 and 0.921, respectively; difference=-0.001; 95% confidence interval (CI): -0.004, 0.001]; P3 outperformed Charlson for overnight hospitalization risk (c-statistics=0.712 and 0.682; difference=0.029; 95% CI: 0.028, 0.031). Adding P3 to a model already containing the M3 index led to only marginal improvement for mortality (difference in c-statistics=0.004; 95% CI: 0.002, 0.005) but some improvement for hospitalization risk (difference in c-statistics=0.020; 95% CI: 0.018, 0.021). CONCLUSIONS: The P3 index provides an appropriate alternative to measures like the Charlson and M3 index when analysts only have access to pharmaceutical dispensing data for determining multimorbidity. The P3 index had a performance advantage over Charlson when analyzing risk for overnight hospital admissions.

Mortality outcomes based on ED qSOFA score and HIV status in a developing low income country.

OBJECTIVE: To evaluate the utility of the quick Sepsis-related Organ Failure Assessment (qSOFA) score to predict risks for emergency department (ED) and hospital mortality among patients in a sub-Saharan Africa (SSA) setting. METHODS: This retrospective cohort study was carried out at a tertiary-care hospital, in Kigali, Rwanda and included patients ≥15years, presenting for ED care during 2013 with an infectious disease (ID). ED and overall hospital mortality were evaluated using multivariable regression, with qSOFA scores as the primary predictor (reference: qSOFA=0), to yield adjusted relative risks (aRR) with 95% confidence intervals (CI). Analyses were performed for the overall population and stratified by HIV status. RESULTS: Among 15,748 cases, 760 met inclusion (HIV infected 197). The most common diagnoses were malaria and intra-abdominal infections. Prevalence of ED and hospital mortality were 12.5% and 25.4% respectively. In the overall population, ED mortality aRR was 4.8 (95% CI 1.9-12.0) for qSOFA scores equal to 1 and 7.8 (95% CI 3.1-19.7) for qSOFA scores ≥2. The aRR for hospital mortality in the overall cohort was 2.6 (95% 1.6-4.1) for qSOFA scores equal to 1 and 3.8 (95% 2.4-6.0) for qSOFA scores ≥2. For HIV infected cases, although proportional mortality increased with greater qSOFA score, statistically significant risk differences were not identified. CONCLUSION: The qSOFA score provided risk stratification for both ED and hospital mortality outcomes in the setting studied, indicating utility in sepsis care in SSA, however, further prospective study in high-burden HIV populations is needed.

Increased frequency of multiple sclerosis among patients with bullous pemphigoid: a population-based cohort study on comorbidities anchored around the diagnosis of bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a disease of the elderly and may be associated with neurological and cardiovascular diseases and diabetes. Mortality rates strongly exceed those of the background population. OBJECTIVES: To investigate the frequency of comorbidities and their temporal relation to BP. METHODS: A register-based matched-cohort study on all Danish patients with a hospital-based diagnosis of BP (n = 3281). The main outcomes were multiple sclerosis (MS), Parkinson disease (PD), Alzheimer disease (AD), stroke, diabetes types 1 and 2, malignancies, ischaemic heart disease (IHD), hypertension and eventually death. RESULTS: At baseline, patients with BP had increased prevalences of MS [odds ratio (OR) 9·7, 95% confidence interval (CI) 6·0-15·6], PD (OR 4·2, 95% CI 3·1-5·8), AD (OR 2·6, 95% CI 1·8-3·5) and stroke (OR 2·7, 95% CI 2·4-2·9). Furthermore, malignancies, cardiovascular disease and diabetes were over-represented among patients with BP: type 1 diabetes (OR 3·1, 95% CI 2·5-3·8), type 2 diabetes (OR 2·3, 95% CI 2·0-2·6), malignancies (OR 1·3, 95% CI 1·1-1·4), IHD (OR 1·7, 95% CI 1·5-1·9) and hypertension (OR 2·0, 95% CI 1·8-2·2). During follow-up, the risk of MS was significantly higher among patients with BP [hazard ratio (HR) 9·4, 95% CI 4·9-18·0], even if events during the first year after diagnosis of BP were excluded (HR 5·1, 95% CI 2·3-11·3). Patients with BP had an average increased mortality rate of 2·04 (95% CI 1·96-2·13). CONCLUSIONS: We discovered a significantly increased frequency of MS among patients with BP. At the time of diagnosis, patients with BP had an excessive number of comorbidities and an increased mortality rate over the following years.

Impact of Multiple Chronic Conditions in Patients Hospitalized with Stroke and Transient Ischemic Attack.

BACKGROUND: The prevalence and clinical impact of chronic conditions (CCs) have increasingly been recognized as an important public health concern. We evaluated the prevalence of coexisting CCs and their association with 30-day mortality and readmission in hospitalized patients with stroke and transient ischemic attack (TIA). METHODS: In a retrospective study of patients aged ≥18 years hospitalized for first-ever stroke and TIA, we assessed the prevalence of coexisting CCs and their predictive value for subsequent 30-day mortality and readmission. RESULTS: Study cohort comprised 6771 patients, hospitalized for stroke (n = 4068) and TIA (n = 2703), 51.4% men, with mean age of 68.2 years (standard deviation: ±15.6), mean number of CCs of 2.9 (±1.7), 30-day mortality rate of 8.6% (entire cohort), and 30-day readmission rate of 9.7% (in 2498 patients limited to Olmsted and surrounding counties). In multivariable models, significant predictors of (1) 30-day mortality were coexisting heart failure (HF) (odds ratio [OR]: 1.45, 95% confidence interval [CI]: 1.09-1.92), cardiac arrhythmia (OR: 1.74, 95% CI: 1.40-2.17), coronary artery disease (CAD) (OR: 1.64, 95% CI: 1.29-2.08), cancer (OR: 1.67, 95% CI: 1.31-2.14), and diabetes (HR: 1.28, 95% CI: 1.01-1.62); and (2) 30-day readmission (n = 2498) were CAD (OR: 1.50, 95% CI: 1.09-2.07), cancer (OR: 1.46, 95% CI: 1.01-2.10), and arthritis (OR: 1.62, 95% CI: 1.09-2.40). CONCLUSIONS: In patients hospitalized with stroke and TIA, CCs are highly prevalent and influence 30-day mortality and readmission. Optimal therapeutic and lifestyle interventions for CAD, HF, cardiac arrhythmia, cancer, diabetes, and arthritis may improve early clinical outcome.

The Association Between Perceived Stress and Mortality Among People With Multimorbidity: A Prospective Population-Based Cohort Study.

Multimorbidity is common and is associated with poor mental health and high mortality. Nevertheless, no studies have evaluated whether mental health may affect the survival of people with multimorbidity. We investigated the association between perceived stress and mortality in people with multimorbidity by following a population-based cohort of 118,410 participants from the Danish National Health Survey 2010 for up to 4 years. Information on perceived stress and lifestyle was obtained from the survey. We assessed multimorbidity using nationwide register data on 39 conditions and identified 4,229 deaths for the 453,648 person-years at risk. Mortality rates rose with increasing levels of stress in a dose-response relationship (P-trend < 0.0001), independently of multimorbidity status. Mortality hazard ratios (highest stress quintile vs. lowest) were 1.51 (95% confidence interval (CI): 1.25, 1.84) among persons without multimorbidity, 1.39 (95% CI: 1.18, 1.64) among those with 2 or 3 conditions, and 1.43 (95% CI: 1.18, 1.73) among those with 4 or more conditions, when adjusted for disease severities, lifestyle, and socioeconomic status. The numbers of excess deaths associated with high stress were 69 among persons without multimorbidity, 128 among those with 2 or 3 conditions, and 255 among those with 4 or more conditions. Our findings suggested that perceived stress contributes significantly to higher mortality rates in a dose-response pattern, and more stress-associated deaths occurred in people with multimorbidity.

Moderation effect of mammography screening among women with multiple chronic conditions.

Comorbidity substantially affects breast cancer risk and prognosis. However, women with chronic conditions are less likely to participate in mammography screening. Few studies have examined potential benefits of mammography in women with chronic conditions. This study investigated the moderation effects of mammography screening on early stage breast cancer and all-cause mortality among women aged 50-69 years with chronic conditions in Taiwan. We used a matched cohort design with four nationwide population databases, and an exact matching approach to match groups with different chronic conditions. Women population aged 50-69 years in 2010 in Taiwan were studied. A generic Charlson comorbidity index (CCI) measure was used to identify chronic illness burden. The sample sizes of each paired matched group with CCI scores of 0, 1, 2, or 3+ were 170,979 using a 1-to-1 exact matching. Conditional logistic regressions with interaction terms were used to test moderation effect, and adjusted predicted probabilities and marginal effects to quantify average and incremental chronic conditions associated with outcome measures. Statistical analyses were conducted in 2020-2021. Women with more chronic conditions were less likely to participate in mammography screening or to receive early breast cancer diagnoses, but were at greater risk of mortality. However, mammography participation increased the likelihood of early breast cancer diagnosis (OR 1.48, 95% CI 1.36-1.60) and decreased risk of all-cause mortality (HR 0.53, 95% CI 0.51-0.55). The interaction terms of CCI and mammography participation indicated significantly increased benefits of early breast cancer diagnosis and decreased risk of all-cause mortality as chronic illness increased. Mammography participation significantly moderated the link between comorbidity and outcome measures among women with chronic conditions. Hence, it is important for public health policy to promote mammography participation for women with multiple chronic conditions.

One in four die from acute infectious illness in an emergency department in Eastern Cape Province, South Africa.

BACKGROUND: Despite the breadth of data supporting evidence-based practice for sepsis care in high-resource settings, there are relatively few data to guide the management of sepsis in low-resource settings, particularly in areas where HIV and tuberculosis (TB) are prevalent. Furthermore, few studies had broadened sepsis parameters to include all patients with acute infectious illness or followed patients up after hospital discharge. Understanding the epidemiology and outcomes of acute infections in a local context is the critical first step to developing locally informed targeted management strategies. OBJECTIVES: To quantify and describe the incidence of and risk factors for mortality in a cohort of patients with undifferentiated acute infectious illnesses who presented to an emergency department (ED) in the Eastern Cape region of South Africa (SA). METHODS: In this prospective cohort study, patients with suspected acute infectious illness were enrolled at a district casualty ward in Mthatha, SA, between 1 July and 1 September 2017. Demographic data, interventions, diagnostic studies and disposition were prospectively collected during the initial encounter and during the hospital stay. Follow-up was conducted both in hospital and via phone interviews 30 days after the index visit. RESULTS: A total of 301 patients presented to the ED with acute infectious illness during the study period, of whom 54.8% had complete 30-day follow-up. Of the study population, only 5.7% had a complete set of vital signs (heart rate, respiratory rate, blood pressure and temperature) documented. Of the cohort, 51.8% had HIV and 32.9% active or treated TB; 25.2% of patients died within 30 days. Accounting for medical history, diagnosis and ED interventions, risk of mortality was independently associated with age (odds ratio (OR) 1.03; 95% confidence interval (CI) 1.00 - 1.06), HIV-positive status (OR 4.10; 95% CI 1.44 - 11.67) and Quick Sequential (Sepsis-Related) Organ Failure Assessment (qSOFA) score (OR 1.90; 95% CI 1.14 - 3.19) in an adjusted model. No ED interventions were protective for mortality, with intravenous fluid administration associated with increased 30-day mortality in this cohort (OR 3.65; 95% CI 1.38 - 9.62). CONCLUSIONS: Among adults with suspected acute infectious illness in Mthatha, SA, 30-day mortality was concerningly high. Mortality was highest in patients with concomitant HIV infection. In particular, vital sign assessment to identify possible sepsis in this cohort is crucial, as it affects mortality to a meaningful extent, yet is often unavailable. Future research is needed on the management of sepsis in low-resource settings, particularly in HIV-positive individuals.

Disparities in diabetes-related multiple chronic conditions and mortality: The influence of race.

AIMS: The aims of this study are to confirm disparities in diabetes mortality rates based on race, determine if race predicts combinations of diabetes and multiple chronic conditions (MCC) that are leading causes of death (LCD), and determine if combinations of diabetes plus MCC mediate the relationship between race and mortality. METHODS: We performed a retrospective cohort study of 443,932 Medicare beneficiaries in the State of Michigan with type 2 diabetes mellitus and MCC. We applied Cox proportional hazards regression to determine predictors of mortality. We applied multinomial logistic regression to determine predictors of MCC combinations. RESULTS: We found that race influences mortality in Medicare beneficiaries with Type 2 diabetes mellitus and MCC. Prior to adjusting for MCC combinations, we observed that Blacks and American Indian/Alaska Natives have increased risk of mortality compared to Whites, while there is no difference in mortality between Hispanics and Whites. Regarding MCC combinations, Black/African American beneficiaries experience increased odds for most MCC combinations while Asian/Pacific Islanders and Hispanics experience lower odds for MCC combinations, compared to Whites. When adjusting for MCC, mortality disparities observed between Whites, Black/African Americans, and American Indians/Alaska Natives persist. CONCLUSIONS: Compared to Whites, Black/African Americans in our cohort had increased odds of most MCC combinations, and an increased risk of mortality that persisted even after adjusting for MCC combinations.

Balance of benefits and harms of different blood pressure targets in people with multiple chronic conditions: a quantitative benefit-harm assessment.

OBJECTIVE: Recent studies suggest that a systolic blood pressure (SBP) target of 120 mm Hg is appropriate for people with hypertension, but this is debated particularly in people with multiple chronic conditions (MCC). We aimed to quantitatively determine whether benefits of a lower SBP target justify increased risks of harm in people with MCC, considering patient-valued outcomes and their relative importance. DESIGN: Highly stratified quantitative benefit-harm assessment based on various input data identified as the most valid and applicable from a systematic review of evidence and based on weights from a patient preference survey. SETTING: Outpatient care. PARTICIPANTS: Hypertensive patients, grouped by age, gender, prior history of stroke, chronic heart failure, chronic kidney disease and type 2 diabetes mellitus. INTERVENTIONS: SBP target of 120 versus 140 mm Hg for patients without history of stroke. PRIMARY AND SECONDARY OUTCOME MEASURES: Probability that the benefits of a SBP target of 120 mm Hg outweigh the harms compared with 140 mm Hg over 5 years (primary) with thresholds >0.6 (120 mm Hg better), <0.4 (140 mm Hg better) and 0.4 to 0.6 (unclear), number of prevented clinical events (secondary), calculated with the Gail/National Cancer Institute approach. RESULTS: Considering individual patient preferences had a substantial impact on the benefit-harm balance. With average preferences, 120 mm Hg was the better target compared with 140 mm Hg for many subgroups of patients without prior stroke, especially in patients over 75. For women below 65 with chronic kidney disease and without diabetes and prior stroke, 140 mm Hg was better. The analyses did not include mild adverse effects, and apply only to patients who tolerate antihypertensive treatment. CONCLUSIONS: For most patients, a lower SBP target was beneficial, but this depended also on individual preferences, implying individual decision-making is important. Our modelling allows for individualised treatment targets based on patient preferences, age, gender and co-morbidities.

Relevance of Polypharmacy for Clinical Outcome in Patients Receiving Vitamin K Antagonists.

BACKGROUND: Although polypharmacy is associated with a negative clinical outcome in various settings and commonly observed in patients receiving oral anticoagulation therapy, evidence on the relevance for the clinical outcome of anticoagulated patients is currently limited. The aim of the study was to investigate the effect of polypharmacy on the clinical outcomes among patients taking phenprocoumon. DESIGN: Prospective cohort study. SETTING: Regular medical care. PARTICIPANTS: Information on 2011 individuals receiving vitamin K antagonists was available for analysis from the prospective multicenter thrombEVAL study. MEASUREMENTS: Data were obtained from clinical visits, computer-assisted interviews, and laboratory measurements. Information on clinical outcome was obtained during a 3-year follow-up period and subsequently validated via medical records. RESULTS: The prevalence of polypharmacy (five drugs or more) was 84.1% (n = 1691). Quality of anticoagulation therapy assessed by time in therapeutic range was lower in individuals on five to eight drugs and nine drugs or more (70.7% and 64.7%, respectively) compared with subjects without polypharmacy (73.4%). In addition, a significantly higher variability of international normalized ratio measurements was found in the presence of polypharmacy. The cumulative incidence of bleeding, hospitalization, and all-cause mortality, but not for thromboembolic events, increased across groups of medication. In adjusted Cox regression analysis, polypharmacy is an independent risk factor for bleeding (hazard ratio [HR]≥ 9 drugs vs 1-4 drugs = 1.62; 95% confidence interval [CI] = 1.04-2.52; p = .033); hospitalization (HR≥ 9 drugs vs 1-4 drugs = 1.60; 95% CI = 1.26-2.03; p < .001; and all-cause mortality (HR≥ 9 drugs vs 1-4 drugs = 2.16; 95% CI = 1.43-3.27; p < .001) in a dose-dependent relationship. Per additional drug, bleeding risk was increased by 4%. CONCLUSIONS: Polypharmacy influences the quality of anticoagulation therapy and translates into an elevated risk of adverse events in anticoagulated patients. This suggests that additional medication intake in such patients should be critically reviewed by physicians, and it highlights the importance of initiating investigations aimed at reducing multiple medication intake. J Am Geriatr Soc 67:463-470, 2019.

Advanced serious illness, multimorbidity, and multibeneficence: The role of communication.

Sturmberg et al write about multimorbidity as "several diagnosable diseases within the same individual." They posit that this syndrome is the result of multiple interconnected disturbances reflecting scale-free, fractal signs of pathology ranging from biochemical/hormonal alterations at one end of a spectrum to community and societal ills at the other. In this commentary, I will be focusing on 3 perspectives: 1) a preterminal phase of multimorbidity that is indicative of that loss of reparative or even homeokinetic properties, known by some as "advanced serious illness"; 2) the manifestations of advanced serious illness multimorbidity that, using the same networks that connect into the patient, are signs of this syndrome at the levels of the immediate family/friend social network, the broader community, and society at large; and 3) the potential for these same networks that transmit pathological forces to convey the positive effects of therapeutic interventions in a scale-free manner, with a focus on how conversation can lead to what I'm calling "multibeneficence."

Multiple chronic condition profiles and survival among oldest-old male patients with hip fracture.

To improve understanding of survival among very elderly male patients with surgically repaired hip fractures, this study applied classification techniques to multiple chronic conditions (MCC) then modeled survival by latent class. Veterans Health Administration (VHA)'s electronic medical records on male inpatients age 85-100 years (n=896) with hip fracture diagnosis and repair were used. MCC defined by Charlson and Elixhauser disorders, medications, demographic covariates, and 5 years follow-up survival were included. Latent Class Analysis (LCA) identified three classes based on patterns of MCC, medications, and demographic covariates: Low-comorbidity (16%), High-longevity (55%), and High-comorbidity (29%). Overall, survival censored at 5 years post-op averaged 717days. The Low-comorbidity group was more likely to be Hispanic, less disabled per VHA determination of eligibility for care, with less risk of postoperative emergency department (ED) visit, and taking no prescription medications. The High-longevity group had longer survival. The High-comorbidity group had more MCC, more prescription medications and shorter survival than the other two groups. Accelerated failure time (AFT) modeled associations between MCC and 5-year survival by class. In AFT models, fewer days until first postoperative ED visit was significantly associated with survival across the three classes. About one in male hip fractured veteran patients over the age of 85 had high levels of MCC and ED use and experienced shorter survival. Hip fracture patients with MCC may merit enhanced post-discharge management. Close investigation targeted to MCC and hip fractures is needed to optimize clinical practices for oldest-old patients in community healthcare systems as well as VHA.

The effect of telehealth, telephone support or usual care on quality of life, mortality and healthcare utilization in elderly high-risk patients with multiple chronic conditions. A prospective study.

BACKGROUND AND OBJECTIVE: To assess the effect of home based telehealth or structured telephone support interventions with respect to usual care on quality of life, mortality and healthcare utilization in elderly high-risk multiple chronic condition patients. PATIENTS AND METHODS: 472 elderly high-risk patients with plurimorbidity in the region of Valencia (Spain) were recruited between June 2012 and May 2013, and followed for 12 months from recruitment. Patients were allocated to either: (a) a structured telephone intervention, a nurse-led case management program with telephone follow up every 15 days; (b) telehealth, which adds technology for remote self-management and the exchange of clinical data; or (c) usual care. Main outcome measures was quality of life measured by the EuroQol (EQ-5D) instrument, cognitive impairment, functional status, mortality and healthcare resource use. Inadequate randomization process led us to used propensity scores for adjusted analyses to control for imbalances between groups at baseline. RESULTS: EQ-5D score was significantly higher in the telehealth group compared to usual care (diff: 0.19, 0.08-0.30), but was not different to telephone support (diff: 0.04, -0.05 to 0.14). In adjusted analyses, inclusion in the telehealth group was associated with an additional 0.18 points in the EQ-5D score compared to usual care at 12 months (p<0.001), and with a gain of 0.13 points for the telephone support group (p<0.001). No differences in mortality or utilization were found, except for a borderline significant increase in General Practitioner visits. CONCLUSIONS: Telehealth was associated with better quality of life. Important limitations of the study and similarity of effects to telephone intervention call for careful endorsement of telemedicine. Clinicaltrials.gov (identifier: NCT02447562).

Multimorbid outpatients: A high frequency of FP appointments and/or family difficulties, should alert FPs to the possibility of death or acute hospitalization occurring within six months; A primary care feasibility study.

BACKGROUND: The European General Practitioners Research Network (EGPRN) designed and validated a comprehensive definition of multimorbidity using a systematic literature review and qualitative research throughout Europe. This definition was tested as a model to assess death or acute hospitalization in multimorbid outpatients. OBJECTIVE: To assess which criteria in the EGPRN concept of multimorbidity could detect outpatients at risk of death or acute hospitalization in a primary care cohort at a 6-month follow-up and to assess whether a large scale cohort with FPs would be feasible. METHOD: Family Physicians included a random sample of multimorbid patients who attended appointments in their offices from July to December 2014. Inclusion criteria were those of the EGPRN definition of Multimorbidity. Exclusion criteria were patients under legal protection and those unable to complete the 2-year follow-up. Statistical analysis was undertaken with uni- and multivariate analysis at a 6-month follow-up using a combination of approaches including both automatic classification and expert decision making. A Multiple Correspondence Analysis (MCA) completed the process with a projection of illustrative variables. A logistic regression was finally performed in order to identify and quantify risk factors for decompensation. RESULTS: 19 FPs participated in the study. 96 patients were analyzed. 3 different clusters were identified. MCA showed the central function of psychosocial factors and peaceful versus conflictual relationships with relatives in all clusters. While taking into account the limit of a small cohort, age, frequency of family physician visits and extent of family difficulties were the factors which predicted death or acute hospitalization. CONCLUSION: A large scale cohort seems feasible in primary care. A sense of alarm should be triggered to prevent death or acute hospitalization in multimorbid older outpatients who have frequent family physician visits and who experience family difficulties.

Effect of early hospital readmission and comorbid conditions on subsequent long-term mortality after transient ischemic attack.

Background: The implications of early readmission on long-term mortality after transient ischemic attack (TIA) are not known. We aimed at examining the effect of 180-day readmission on subsequent long-term mortality after index hospitalization for TIA. Methods: A retrospective study of patients hospitalized for first-ever TIA at Mayo Clinic from 2000 through 2017. Patients readmitted within 180 days postdischarge were compared with those not readmitted in long-term risk of death. Results: Of 251 TIA patients aged 73 ± 15 years with 1509 person-years of follow-up, 65 (26%) were readmitted within 180 days of discharge and 125 died during a median follow-up of 5.7 years. The mortality was 10 vs. 7 deaths per 100 person-years in patients who were readmitted compared to those who were not readmitted with hazard ratio (HR) 1.73 (95% confidence interval [CI] 1.13-2.66). Other competing predictors of mortality were age ≥65 years (HR 5.70, 95% CI 2.72-11.96), cancer (HR 1.65, 95% CI 1.03-3.38), chronic obstructive pulmonary disease (HR 1.90, 95% CI 1.07-3.38), heart failure (HR 3.03, 95% CI 1.82-5.06), dementia (HR 5.87, 95% CI 3.27-10.52), creatinine ≥1.4 mg/dl (HR 1.89, 95% CI 1.17-3.06), and hemoglobin level <10 g/dl (HR 2.80, 95% CI 1.20-6.66). Conclusions: Hospital readmission within 180 days of discharge from index TIA was associated with increased risk of death several years after initial readmission. Older age and several comorbidities identified during index hospitalization also confer increased risk for long-term mortality.

SIRT1 Polymorphisms and Serum-Induced SIRT1 Protein Expression in Aging and Frailty: The CHAMP Study.

The nutrient sensing protein, SIRT1 influences aging and nutritional interventions such as caloric restriction in animals, however, the role of SIRT1 in human aging remains unclear. Here, the role of SIRT1 single-nucleotide polymorphisms (SNPs) and serum-induced SIRT1 protein expression (a novel assay that detects circulating factors that influence SIRT1 expression in vitro) were studied in the Concord Health and Ageing in Men Project (CHAMP), a prospective cohort of community dwelling men aged 70 years and older. Serum-induced SIRT1 expression was not associated with age or mortality, however participants within the lowest quintile were less likely to be frail (odds ratio (OR) 0.34, 95% confidence interval (CI) 0.17-0.69, N = 1,309). Serum-induced SIRT1 expression was associated with some markers of body composition and nutrition (height, weight, body fat and lean % mass, albumin, and cholesterol) but not disease. SIRT1 SNPs rs2273773, rs3740051, and rs3758391 showed no association with age, frailty, or mortality but were associated with weight, height, body fat and lean, and albumin levels. There were some weak associations between SIRT1 SNPs and arthritis, heart attack, deafness, and cognitive impairment. There was no association between SIRT1 SNPs and the serum-induced SIRT1 assay. SIRT1 SNPs and serum-induced SIRT1 expression in older men may be more closely associated with nutrition and body composition than aging and age-related conditions.

Associations Between Short or Long Length of Stay and 30-Day Readmission and Mortality in Hospitalized Patients With Heart Failure.

OBJECTIVES: This study sought to examine the associations between heart failure (HF)-related hospital length of stay and 30-day readmissions and HF hospital length of stay and mortality rates. BACKGROUND: Although reducing HF readmission and mortality rates are health care priorities, how HF-related hospital length of stay affects these outcomes is not fully known. METHODS: A population-level, multicenter cohort study of 58,230 patients with HF (age >65 years) was conducted in Ontario, Canada between April 1, 2003 and March 31, 2012. RESULTS: When length of stay was modeled as continuous variable, its association with the rate of cardiovascular readmission was nonlinear (p < 0.001 for nonlinearity) and U-shaped. When analyzed as a categorical variable, there was a higher rate of cardiovascular readmission for short (1 to 2 days; adjusted hazard ratio [HR]: 1.12; 95% confidence interval [CI]: 1.04 to 1.21; p = 0.003) and long (9 to 14 days; HR: 1.11; 95% CI: 1.04 to 1.19; p = 0.002) lengths of stay as compared with 5 to 6 days (reference). Hospital readmissions for HF demonstrated a similar nonlinear (p = 0.005 for nonlinearity) U-shaped relationship with increased rates for short (HR: 1.15; 95% CI: 1.04 to 1.27; p = 0.006) and long (HR: 1.14; 95% CI: 1.04 to 1.25; p = 0.004) lengths of stay. Noncardiovascular readmissions demonstrated increased rates with long (HR: 1.17; 95% CI: 1.07 to 1.29; p < 0.001) and decreased rates with short (HR: 0.87; 95% CI: 0.79 to 0.96; p = 0.006) lengths of stay (p = 0.53 for nonlinearity). The 30-day mortality risk was highest after a long length of stay (HR: 1.28; 95% CI: 1.14 to 1.43; p < 0.001). CONCLUSIONS: A short length of stay after hospitalization for HF is associated with increased rates of cardiovascular and HF readmissions but lower rates of noncardiovascular readmissions. A long length of stay is associated with increased rates of all types of readmission and mortality.

The quest for sustained multiple morbidity reduction in very low-birth-weight infants: the Antifragility project.

OBJECTIVE: Can a comprehensive, explicitly directive evidence-based guideline for all therapies that might affect the major morbidities of very low-birth-weight (VLBW) infants help a neonatal intensive care unit (NICU) further improve generally favorable morbidity rates? Can Antifragility principles of provider adaptive growth from stressors, enhanced infant risk assessment and adherence to effective therapies minimize unproven treatments and reduce all morbidities? STUDY DESIGN: Prospectively planned observational trial in VLBW infants: control group born October 2011 to September 2013 and study group October 2013 to September 2015. Multi-disciplinary evidence-based review assigned all NICU treatments into one of four distinct categories: (1) always employ this therapy for VLBW infants, (2) never use this therapy, (3) employ this questionable therapy thoughtfully, only in certain circumstances and (4) this therapy has insufficient evidence of efficacy and safety. Extensive staff education emphasized evidence-based potentially better practice (PBP) selection with compliance checks, appreciation of intertwined co-morbidities and prioritizing infant risk reduction strategies. RESULTS: Control included 221 infants, mean (s.d.) age 29 (2.6) weeks, birth weight 1129 (257) g and Study included 197 infants, 29 (2.7) weeks, 1093 (292) g. One hundred and four distinct therapies were placed into categories 1 to 4, with 32 specific compliance checks. Overall mean compliance with the process checks during the second era was 70%, high: 100% (exclusive breast milk use), low: 24% (correct pulse oximetry alarm settings). Morbidity and mortality rates did not significantly change during the second era. CONCLUSIONS: In our NICU with favorable morbidity rates, an expanded effort using a comprehensive therapy guideline for VLBW infants did not further improve outcomes. We need deeper understanding of continuous quality improvement (CQI) fundamentals, therapy compliance, co-morbidity relationships and enhanced sensitivity of risk assessment. Our innovative Antifragility PBP guideline could be useful to other NICUs seeking improvement in VLBW infant morbidities, as we offer a reasoned and concise template of a broad array of therapies categorized efficiently for transparency and review, designed to enhance responsible CQI decision-making.

Physical Activity and the Effect of Multimorbidity on All-Cause Mortality in Older Adults.

OBJECTIVE: To examine the stratified and joint associations of physical activity (PA) and the number of chronic conditions on long-term all-cause mortality. PATIENTS AND METHODS: We used data from a cohort of 3967 individuals representative of the noninstitutionalized population 60 years and older in Spain (2000/2001). Information on self-reported PA (inactive, occasionally, monthly, weekly) and 11 chronic conditions diagnosed by a physician and reported by the study participants were recorded. Associations are summarized using hazard ratios (HRs) and Cox regression, after adjustment for covariates. RESULTS: At baseline, 43.2%, 37.5%, 14.4%, and 4.9% of participants had 0, 1, 2, and 3 or more chronic conditions, respectively. Mean follow-up was 8.9 years (median, 10.8 years; range, 0.02-11.28 years), with 1483 deaths. The HRs (95% CIs) for all-cause mortality in participants with 1, 2, and 3 or more chronic conditions compared with those with none were 1.26 (1.05-1.39), 1.78 (1.51-2.09), and 2.27 (1.79-2.86), respectively. Being physically active (ie, doing any PA) was associated with a mortality reduction (95% CI) of 30% (14%-43%), 33% (18%-45%), 35% (16%-50%), and 47% (18%-66%) in participants with 0, 1, 2, and 3 or more chronic conditions, respectively. Compared with those with 0 chronic conditions who were physically active, participants with 2 (HR=2.63; 95% CI, 2.09-3.31) and 3 or more (HR=3.26; 95% CI, 2.42-4.38) chronic conditions who were physically inactive had the highest mortality risk. CONCLUSION: Physical activity is associated with a reduction in increased risk of death associated with multimorbidity (ie, coexistence of ≥2 chronic conditions) in older individuals.