Redefining Aging in HIV Infection Using Phenotypes

Purpose of review: This article critically reviews the utility of “phenotypes” as behavioral descriptors in aging/HIV research that inform biological underpinnings and treatment development. We adopt a phenotypic redefinition of aging conceptualized within a broader context of HIV infection and of aging. Phenotypes are defined as dimensions of behavior, closely related to fundamental mechanisms, and, thus, may be more informative than chronological age. Primary emphasis in this review is given to comorbid aging and cognitive aging, though other phenotypes (i.e., disability, frailty, accelerated aging, successful aging) are also discussed in relation to comorbid aging and cognitive aging. Recent findings: The main findings that emerged from this review are as follows: (1) the phenotypes, comorbid aging and cognitive aging, are distinct from each other, yet overlapping; (2) associative relationships are the rule in HIV for comorbid and cognitive aging phenotypes; and (3) HIV behavioral interventions for both comorbid aging and cognitive aging have been limited. Summary: Three paths for research progress are identified for phenotype-defined aging/HIV research (i.e., clinical and behavioral specification, biological mechanisms, intervention targets), and some important research questions are suggested within each of these research paths

Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study

Predictors and consequences of altered mineral metabolism: The Dialysis Outcomes and Practice Patterns Study.BackgroundAltered mineral metabolism contributes to bone disease, cardiovascular disease, and other clinical problems in patients with end-stage renal disease.MethodsThis study describes the recent status, significant predictors, and potential consequences of abnormal mineral metabolism in representative groups of hemodialysis facilities (N = 307) and patients (N = 17,236) participating in the Dialysis Outcomes and Practice Patterns Study (DOPPS) in the United States, Europe, and Japan from 1996 to 2001.ResultsMany patients fell out of the recommended guideline range for serum concentrations of phosphorus (8% of patients below lower target range, 52% of patients above upper target range), albumin-corrected calcium (9% below, 50% above), calcium-phosphorus product (44% above), and intact PTH (51% below, 27% above). All-cause mortality was significantly and independently associated with serum concentrations of phosphorus (RR 1.04 per 1 mg/dL, P = 0.0003), calcium (RR 1.10 per 1 mg/dL, P < 0.0001), calcium-phosphorus product (RR 1.02 per 5 mg2/dL2, P = 0.0001), PTH (1.01 per 100 pg/dL, P = 0.04), and dialysate calcium (RR 1.13 per 1 mEq/L, P = 0.01). Cardiovascular mortality was significantly associated with the serum concentrations of phosphorus (RR 1.09, P < 0.0001), calcium (RR 1.14, P < 0.0001), calcium-phosphorus product (RR 1.05, P < 0.0001), and PTH (RR 1.02, P = 0.03). The adjusted rate of parathyroidectomy varied 4-fold across the DOPPS countries, and was significantly associated with baseline concentrations of phosphorus (RR 1.17, P < 0.0001), calcium (RR 1.58, P < 0.0001), calcium-phosphorus product (RR 1.11, P < 0.0001), PTH (RR 1.07, P < 0.0001), and dialysate calcium concentration (RR 0.57, P = 0.03). Overall, 52% of patients received some form of vitamin D therapy, with parenteral forms almost exclusively restricted to the United States. Vitamin D was potentially underused in up to 34% of patients with high PTH, and overused in up to 46% of patients with low PTH. Phosphorus binders (mostly calcium salts during the study period) were used by 81% of patients, with potential overuse in up to 77% patients with low serum phosphorus concentration, and potential underuse in up to 18% of patients with a high serum phosphorus concentration.ConclusionThis study expands our understanding of the relationship between altered mineral metabolism and outcomes and identifies several potential opportunities for improved practice in this area

Predicting Cognitive Decline in Nondemented Elders Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration

BACKGROUND AND OBJECTIVES: Dementia is a growing socio-economic challenge that requires early intervention. Identifying biomarkers that reliably predict clinical progression early in the disease process would better aid selection of individuals for future trial participation. Here we compared the ability of baseline, single time-point biomarkers (CSF amyloid 1-42, CSF ptau-181, white matter hyperintensities (WMH), cerebral microbleeds (CMB), whole-brain volume, and hippocampal volume) to predict decline in cognitively normal individuals who later converted to mild cognitive impairment (MCI) (CNtoMCI), and those with MCI who later converted to an Alzheimer's disease (AD) diagnosis (MCItoAD). METHODS: Standardised baseline biomarker data from ADNI2/Go, and longitudinal diagnostic data (including ADNI3), were used. Cox regression models assessed biomarkers in relation to time to change in clinical diagnosis using all follow-up timepoints available. Models were fit for biomarkers univariately, and together in a multivariable model. Hazard Ratios (HR) were compared to evaluate biomarkers. Analyses were performed separately in CNtoMCI and MCItoAD groups. RESULTS: For CNtoMCI (n = 189), there was strong evidence that higher WMH volume (individual model: HR 1.79, p = .002; fully-adjusted model: HR 1.98, p = .003), and lower hippocampal volume (individual: HR 0.54, p = .001; fully-adjusted: HR 0.40, p < .001) were associated with conversion to MCI individually and independently. For MCItoAD (n = 345), lower hippocampal (individual model: HR 0.45, p < .001; fully-adjusted model: HR 0.55, p < .001) and whole-brain volume (individual: HR 0.31, p < .001; fully-adjusted: HR 0.48, p = .02), increased CSF ptau (individual: HR 1.88, p < .001; fully-adjusted: HR 1.61, p < .001), and lower CSF amyloid (individual: HR 0.37, p < .001, fully-adjusted: HR 0.62, p = .008) were most strongly associated with conversion to AD individually and independently. DISCUSSION: Lower hippocampal volume was a consistent predictor of clinical conversion to MCI and AD. CSF and brain volume biomarkers were predictive of conversion to AD from MCI, while WMH were predictive of conversion to MCI from cognitively normal. The predictive ability of WMH in the CNtoMCI group may be interpreted as some being on a different pathological pathway, such as vascular cognitive impairment

Depression as a predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe

Depression as a predictor of mortality and hospitalization among hemodialysis patients in the United States and Europe.BackgroundDepression is not uncommon among patients with end-stage renal disease (ESRD) being treated by hemodialysis. We investigated whether risk of mortality and rate of hospitalization may be predicted from physician-diagnosed depression and patients' self-reports of depressive symptoms.MethodsData were analyzed from the Dialysis Outcomes and Practice Patterns Study (DOPPS) for randomly selected ESRD patients being treated by hemodialysis in the United States (142 facilities, 2855 patients) and five European countries (101 facilities, 2401 patients). The diagnosis of depression during the past year was abstracted from the medical records. In addition, the patients were asked to indicate how much of their time over the previous four weeks they had felt (1) “so down in the dumps that nothing could cheer you up” and (2) “downhearted and blue.” A response of “a good bit,”“most,” or “all” of the time were classified as depressed.ResultsThe prevalence of depression was nearly 20%. The relative risks of mortality and hospitalization among depressed (vs. non-depressed), adjusted for time on dialysis, age, race, socioeconomic status, comorbid indicators and country were, respectively: 1.23 and 1.11 for physician-diagnosed depression, 1.48 and 1.15 for the “so down in the dumps” question, and 1.35 and 1.11 for the “downhearted and blue” question (P < 0.05 for all six relative risks). These associations were not significantly different between US and European patients.ConclusionsSelf-reported depression by two simple questions was associated with increased risks of mortality and hospitalization for hemodialysis patients. Future research needs to assess whether early identification and treatment of depression may help to improve quality of life and survival in hemodialysis patients

Nonadherence in hemodialysis: Associations with mortality, hospitalization, and practice patterns in the DOPPS

Nonadherence in hemodialysis: Associations with mortality, hospitalization, and practice patterns in the DOPPS.BackgroundNonadherence among hemodialysis patients compromises dialysis delivery, which could influence patient morbidity and mortality. The Dialysis Outcomes and Practice Patterns Study (DOPPS) provides a unique opportunity to review this problem and its determinants on a global level.MethodsNonadherence was studied using data from the DOPPS, an international, observational, prospective hemodialysis study. Patients were considered nonadherent if they skipped one or more sessions per month, shortened one or more sessions by more than 10 minutes per month, had a serum potassium level openface>6.0mEq/L, a serum phosphate level openface>7.5mg/dL (>2.4mmol/L), or interdialytic weight gain (IDWG)>5.7% of body weight. Predictors of nonadherence were identified using logistic regression. Survival analysis used the Cox proportional hazards model adjusting for case-mix.ResultsSkipping treatment was associated with increased mortality [relative risk (RR) = 1.30, P = 0.01], as were excessive IDWG (RR = 1.12, P = 0.047) and high phosphate levels (RR = 1.17, P = 0.001). Skipping also was associated with increased hospitalization (RR = 1.13, P = 0.04), as were high phosphate levels (RR = 1.07, P = 0.05). Larger facility size (per 10 patients) was associated with higher odds ratios (OR) of skipping (OR = 1.03, P = 0.06), shortening (OR = 1.03, P = 0.05), and IDWG (OR = 1.02, P = 0.07). An increased percentage of highly trained staff hours was associated with lower OR of skipping (OR = 0.84 per 10%, P = 0.02); presence of a dietitian was associated with lower OR of excessive IDWG (OR = 0.75, P = 0.08).ConclusionNonadherence was associated with increased mortality risk (skipping treatment, excessive IDWG, and high phosphate) and with hospitalization risk (skipping, high phosphate). Certain patient/facility characteristics also were associated with nonadherence

Gaps and opportunities in refractory status epilepticus research in children: A multi-center approach by the Pediatric Status Epilepticus Research Group (pSERG)

PURPOSE: Status epilepticus (SE) is a life-threatening condition that can be refractory to initial treatment. Randomized controlled studies to guide treatment choices, especially beyond first-line drugs, are not available. This report summarizes the evidence that guides the management of refractory convulsive SE (RCSE) in children, defines gaps in our clinical knowledge and describes the development and works of the \u27pediatric Status Epilepticus Research Group\u27 (pSERG). METHODS: A literature review was performed to evaluate current gaps in the pediatric SE and RCSE literature. In person and online meetings helped to develop and expand the pSERG network. RESULTS: The care of pediatric RCSE is largely based on extrapolations of limited evidence derived from adult literature and supplemented with case reports and case series in children. No comparative effectiveness trials have been performed in the pediatric population. Gaps in knowledge include risk factors for SE, biomarkers of SE and RCSE, second- and third-line treatment options, and long-term outcome. CONCLUSION: The care of children with RCSE is based on limited evidence. In order to address these knowledge gaps, the multicenter pSERG was established to facilitate prospective collection, analysis, and sharing of de-identified data and biological specimens from children with RCSE. These data will allow identification of treatment strategies associated with better outcomes and delineate evidence-based interventions to improve the care of children with SE

Predicting Cognitive Decline in Older Adults Using Baseline Metrics of AD Pathologies, Cerebrovascular Disease, and Neurodegeneration

BACKGROUND AND OBJECTIVES: Dementia is a growing socioeconomic challenge that requires early intervention. Identifying biomarkers that reliably predict clinical progression early in the disease process would better aid selection of individuals for future trial participation. Here, we compared the ability of baseline, single time-point biomarkers (CSF amyloid 1-42, CSF ptau-181, white matter hyperintensities (WMH), cerebral microbleeds, whole-brain volume, and hippocampal volume) to predict decline in cognitively normal individuals who later converted to mild cognitive impairment (MCI) (CNtoMCI) and those with MCI who later converted to an Alzheimer disease (AD) diagnosis (MCItoAD). METHODS: Standardized baseline biomarker data from AD Neuroimaging Initiative 2 (ADNI2)/GO and longitudinal diagnostic data (including ADNI3) were used. Cox regression models assessed biomarkers in relation to time to change in clinical diagnosis using all follow-up time points available. Models were fit for biomarkers univariately and together in a multivariable model. Hazard ratios (HRs) were compared to evaluate biomarkers. Analyses were performed separately in CNtoMCI and MCItoAD groups. RESULTS: For CNtoMCI (n = 189), there was strong evidence that higher WMH volume (individual model: HR 1.79, p = 0.002; fully adjusted model: HR 1.98, p = 0.003) and lower hippocampal volume (individual: HR 0.54, p = 0.001; fully adjusted: HR 0.40, p < 0.001) were associated with conversion to MCI individually and independently. For MCItoAD (n = 345), lower hippocampal (individual model: HR 0.45, p < 0.001; fully adjusted model: HR 0.55, p < 0.001) and whole-brain volume (individual: HR 0.31, p < 0.001; fully adjusted: HR 0.48, p = 0.02), increased CSF ptau (individual: HR 1.88, p < 0.001; fully adjusted: HR 1.61, p < 0.001), and lower CSF amyloid (individual: HR 0.37, p < 0.001; fully adjusted: HR 0.62, p = 0.008) were most strongly associated with conversion to AD individually and independently. DISCUSSION: Lower hippocampal volume was a consistent predictor of clinical conversion to MCI and AD. CSF and brain volume biomarkers were predictive of conversion to AD from MCI, whereas WMH were predictive of conversion to MCI from cognitively normal. The predictive ability of WMH in the CNtoMCI group may be interpreted as some being on a different pathologic pathway, such as vascular cognitive impairment

Recovery after spinal cord relapse in multiple sclerosis is predicted by radial diffusivity

Background: The aim of this study was to determine whether the diffusion tensor-derived radial diffusivity and axial diffusivity, measured in the cortico-spinal tract in the cervical cord, predict clinical recovery after a cord relapse in patients with multiple sclerosis, and change over time

Telephone-administered psychotherapy for depression in MS patients: moderating role of social support

Depression is common in individuals with multiple sclerosis (MS). While psychotherapy is an effective treatment for depression, not all individuals benefit. We examined whether baseline social support might differentially affect treatment outcome in 127 participants with MS and depression randomized to either Telephone-administered Cognitive-Behavioral Therapy (T-CBT) or Telephone-administered Emotion-Focused Therapy (T-EFT). We predicted that those with low social support would improve more in T-EFT, since this approach emphasizes the therapeutic relationship, while participants with strong social networks and presumably more emotional resources might fare better in the more structured and demanding T-CBT. We found that both level of received support and satisfaction with that support at baseline did moderate treatment outcome. Individuals with high social support showed a greater reduction in depressive symptoms in the T-CBT as predicted, but participants with low social support showed a similar reduction in both treatments. This suggests that for participants with high social support, CBT may be a more beneficial treatment for depression compared with EFT