[Stress tolerance and quality of life--effect of a comprehensive ambulatory rehabilitation program for patients with chronic heart failure]

Chronic heart failure (CHF) impairs quality of life (QoL) much stronger than other chronic diseases. The objective of this evaluation was to assess the effect of a new integrated comprehensive outpatients rehabilitation program on somatic parameters and quality of life in 51 patients with stable CHF. After rehabilitation, left ventricular ejection fraction, NYHA class, and parameters of sub-maximum and maximum exercise capacity improved significantly between 11 and 20%, and 6-minute walking distance by 58% on average (p < 0.0001). Non-disease specific QoL (Short Form-36 questionnaire) improved in only 2 of 8 subscales (physical functioning [effect size 0.38, p < 0.001], and role functioning [effect size 0.17, p < 0.05]), and a mental component score [effect size 0.47, p < 0.0001]. Disease-specific QoL (Minnesota Living with Heart Failure questionnaire) improved in terms of sum score [effect size 0.24, p < 0.0001], and physical component score [effect size 0.35, p < 0.0001]. Improvement in exercise capacity correlated significantly with improvements in parameters of disease-specific QoL.

Relation of heart rate recovery to psychological distress and quality of life in patients with chronic heart failure

BACKGROUND: Psychological distress, poor disease-specific quality of life (QoL), and reduction in vagally mediated early heart rate recovery (HRR) after exercise, all previously predicted morbidity and mortality in patients with chronic heart failure (CHF). We hypothesized lower HRR with greater psychological distress and poorer QoL in CHF. DESIGN: All assessments were made at the beginning of a comprehensive cardiac outpatient rehabilitation intervention program. METHODS: Fifty-six CHF patients (mean 58+/-12 years, 84% men) completed the Hospital Anxiety and Depression Scale and the Minnesota Living With Heart Failure Questionnaire. HRR was determined as the difference between HR at the end of exercise and 1 min after exercise termination (HRR-1). RESULTS: Elevated levels of anxiety symptoms (P=0.005) as well as decreased levels of the Minnesota Living With Heart Failure Questionnaire total (P = 0.025), physical (P=0.026), and emotional (P=0.017) QoL were independently associated with blunted HRR-1. Anxiety, total, physical, and emotional QoL explained 11.4, 8, 7.8, and 9.0%, respectively, of the variance after controlling for covariates. Depressed mood was not associated with HRR-1 (P=0.20). CONCLUSION: Increased psychological distress with regard to elevated anxiety symptoms and impaired QoL were independent correlates of reduced HRR-1 in patients with CHF. Reduced vagal tone might explain part of the adverse clinical outcome previously observed in CHF patients in relation to psychological distress and poor disease-specific QoL.

Prosthetic Rehabilitation, Implant Survival and Quality of Life 2 to 5 Years after Resection of Oral Tumors

Background: After oral tumor resection, structural and functional rehabilitation by means of dental prostheses is complex, and positive treatment outcome is not always predictable. Purpose: The objective of the study was to report on oral rehabilitation and quality of life 2-5 years after resection of malignant oral tumors. Materials and Methods: Data of 46 patients (57 ± 7 years) who underwent oral tumor surgery were available. More than 50% of tumors were classified T3 or T4. Open oro-nasal defects resulted in 12 patients and full mandibulary block resections in 23 patients. Comprehensive planning, implant placement, and prosthetic rehabilitation followed an interdisciplinary protocol. Analysis comprised tumor location, type of prostheses, implant survival, and quality of life. Results: Because of advanced tumor status, resections resulted in marked alteration of the oral anatomy requiring complex treatment procedures. Prosthetic rehabilitation comprised fixed and removable prostheses, with 104 implants placed in 28 patients (60%). Early implant loss was high (13%) and cumulative survival rate of loaded implants was <90% after 5 years. Prosthetic plans had to be modified because of side effects of tumor therapy, complications with implants and tumor recurrence. The majority of patients rated quality of life favorable, but some experienced impaired swallowing, dry mouth, limited mouth opening, appearance, and soreness. Conclusions: Some local effects of tumor therapy could not be significantly improved by prosthetic rehabilitation leading to functional and emotional disability. Many patients had passed away or felt too ill to fill the questionnaires. This case series confirms the complex anatomic alterations after tumor resection and the need for individual treatment approaches especially regarding prosthesis design. In spite of disease-related local and general restrictions, most patients gave a positive assessment of quality of life.

Mutations in the tight-junction gene claudin 19 (CLDN19) are associated with renal magnesium wasting, renal failure, and severe ocular involvement

Claudins are major components of tight junctions and contribute to the epithelial-barrier function by restricting free diffusion of solutes through the paracellular pathway. We have mapped a new locus for recessive renal magnesium loss on chromosome 1p34.2 and have identified mutations in CLDN19, a member of the claudin multigene family, in patients affected by hypomagnesemia, renal failure, and severe ocular abnormalities. CLDN19 encodes the tight-junction protein claudin-19, and we demonstrate high expression of CLDN19 in renal tubules and the retina. The identified mutations interfere severely with either cell-membrane trafficking or the assembly of the claudin-19 protein. The identification of CLDN19 mutations in patients with chronic renal failure and severe visual impairment supports the fundamental role of claudin-19 for normal renal tubular function and undisturbed organization and development of the retina.

Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice

BACKGROUND: Microarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. METHODS: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. RESULTS: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. CONCLUSIONS: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.

Acute Toxicity and Quality of Life After Dose-Intensified Salvage Radiation Therapy for Biochemically Recurrent Prostate Cancer After Prostatectomy: First Results of the Randomized Trial SAKK 09/10

PURPOSE Patients with biochemical failure (BF) after radical prostatectomy may benefit from dose-intensified salvage radiation therapy (SRT) of the prostate bed. We performed a randomized phase III trial assessing dose intensification. PATIENTS AND METHODS Patients with BF but without evidence of macroscopic disease were randomly assigned to either 64 or 70 Gy. Three-dimensional conformal radiation therapy or intensity-modulated radiation therapy/rotational techniques were used. The primary end point was freedom from BF. Secondary end points were acute toxicity according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.0) and quality of life (QoL) according to the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaires C30 and PR25. RESULTS Three hundred fifty patients were enrolled between February 2011 and April 2014. Three patients withdrew informed consent, and three patients were not eligible, resulting in 344 patients age 48 to 75 years in the safety population. Thirty patients (8.7%) had grade 2 and two patients (0.6%) had grade 3 genitourinary (GU) baseline symptoms. Acute grade 2 and 3 GU toxicity was observed in 22 patients (13.0%) and one patient (0.6%), respectively, with 64 Gy and in 29 patients (16.6%) and three patients (1.7%), respectively, with 70 Gy (P = .2). Baseline grade 2 GI toxicity was observed in one patient (0.6%). Acute grade 2 and 3 GI toxicity was observed in 27 patients (16.0%) and one patient (0.6%), respectively, with 64 Gy, and in 27 patients (15.4%) and four patients (2.3%), respectively, with 70 Gy (P = .8). Changes in early QoL were minor. Patients receiving 70 Gy reported a more pronounced and clinically relevant worsening in urinary symptoms (mean difference in change score between arms, 3.6; P = .02). CONCLUSION Dose-intensified SRT was associated with low rates of acute grade 2 and 3 GU and GI toxicity. The impact of dose-intensified SRT on QoL was minor, except for a significantly greater worsening in urinary symptoms.

Spondylodiscitis in the elderly patient: clinical mid-term results and quality of life

Focusing on spondylodiscitis in elderly patients current literature does not contain much information.

Significance of Periodontal Risk Assessment in the recurrence of periodontitis and tooth loss

Aim: To investigate the association of the Periodontal Risk Assessment (PRA) model categories with periodontitis recurrence and tooth loss during supportive periodontal therapy (SPT) and to explore the role of patient compliance. Material and Methods: In a retrospective cohort, PRA was performed for 160 patients after active periodontal therapy (APT) and after 9.5 ± 4.5 years of SPT. The recurrence of periodontitis and tooth loss were analysed according to the patient's risk profile (low, moderate or high) after APT and compliance with SPT. The association of risk factors with tooth loss and recurrence of periodontitis was investigated using logistic regression analysis. Results: In 18.2% of patients with a low-risk profile, in 42.2% of patients with a moderate-risk profile and in 49.2% of patients with a high-risk profile after APT, periodontitis recurred. During SPT, 1.61 ± 2.8 teeth/patient were lost. High-risk profile patients lost significantly more teeth (2.59 ± 3.9) than patients with moderate- (1.02 ± 1.8) or low-risk profiles (1.18 ± 1.9) (Kruskal–Wallis test, p=0.0229). Patients with erratic compliance lost significantly (Kruskal–Wallis test, p=0.0067) more teeth (3.11 ± 4.5) than patients compliant with SPT (1.07 ± 1.6). Conclusions: In multivariate logistic regression analysis, a high-risk patient profile according to the PRA model at the end of APT was associated with recurrence of periodontitis. Another significant factor for recurrence of periodontitis was an SPT duration of more than 10 years.

Inhibition of the kynurenine-NAD+ pathway leads to energy failure and exacerbates apoptosis in pneumococcal meningitis

Pneumococcal meningitis causes neurological sequelae, including learning and memory deficits in up to half of the survivors. In both humans and in animal models of the disease, there is apoptotic cell death in the hippocampus, a brain region involved in learning and memory function. We previously demonstrated that in an infant rat model of pneumococcal meningitis, there is activation of the kynurenine (KYN) pathway in the hippocampus, and that there was a positive correlation between the concentration of 3-hydroxykynurenine and the extent of hippocampal apoptosis. To clarify the role of the KYN pathway in the pathogenesis of hippocampal apoptosis in pneumococcal meningitis, we specifically inhibited 2 key enzymes of the KYN pathway and assessed hippocampal apoptosis, KYN pathway metabolites, and nicotinamide adenine dinucleotide (NAD) concentrations by high-performance liquid chromatography. Pharmacological inhibition of kynurenine 3-hydroxylase and kynureninase led to decreased cellular NAD levels and increased apoptosis in the hippocampus. The cerebrospinal fluid levels of tumor necrosis factor and interleukin-1? and -? were not affected. Our data suggest that activation of the KYN pathway in pneumococcal meningitis is neuroprotective by compensating for an increased NAD demand caused by infection and inflammation;this mechanism may prevent energy failure and apoptosis in the hippocampus.

Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries

Context Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. Objectives To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. Design, Setting, and Participants Multicohort study of 632 patients >14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. Main Outcome Measures Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. Results The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for <80% vs ≥95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/μL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/μL vs 200/μL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. Conclusions Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.

Longitudinal patterns in survival, comorbidity, healthcare utilization and quality of care among older women following breast cancer diagnosis

OBJECTIVES To compare longitudinal patterns of health care utilization and quality of care for other health conditions between breast cancer-surviving older women and a matched cohort without breast cancer. DESIGN Prospective five-year longitudinal comparison of cases and matched controls. SUBJECTS Newly identified breast cancer patients recruited during 1997–1999 from four geographic regions (Los Angeles, CA; Minnesota; North Carolina; and Rhode Island; N = 422) were matched by age, race, baseline comorbidity and zip code location with up to four non-breast-cancer controls (N = 1,656). OUTCOMES Survival; numbers of hospitalized days and physician visits; total inpatient and outpatient Medicare payments; guideline monitoring for patients with cardiovascular disease and diabetes, and bone density testing and colorectal cancer screening. RESULTS Five-year survival was similar for cases and controls (80% and 82%, respectively; p = 0.18). In the first follow-up year, comorbidity burden and health care utilization were higher for cases (p < 0.01), with most differences diminishing over time. However, the number of physician visits was higher for cases (p < 0.01) in every year, driven partly by more cancer and surgical specialist visits. Cases and controls adhered similarly to recommended bone density testing, and monitoring of cardiovascular disease and diabetes; adherence to recommended colorectal cancer screening was better among cases. CONCLUSION Breast cancer survivors’ health care utilization and disease burden return to pre-diagnosis levels after one year, yet their greater use of outpatient care persists at least five years. Quality of care for other chronic health problems is similar for cases and controls.