Measuring frailty in clinical practice: a comparison of physical frailty assessment methods in a geriatric out-patient clinic.

BACKGROUND: The objectives of this study were to determine: 1) the prevalence of frailty using Fried's phenotype method and the Short Performance Physical Battery (SPPB), 2) agreement between frailty assessment methods, 3) the feasibility of assessing frailty using Fried's phenotype method and the SPPB. METHODS: This cross-sectional study was conducted at a geriatric out-patient clinic in Hamilton, Canada. A research assistant conducted all frailty assessments. Patients were classified as non-frail, pre-frail or frail according to Fried's phenotype method and the SPPB. Agreement among methods is reported using the Cohen kappa statistic (standard error). Feasibility data included the percent of eligible participants agreeing to attempt the frailty assessments (criterion for feasibility: ≥90% of patients agreeing to the frailty assessment), equipment required, and safety considerations. A p-value of <0.05 is considered significant. RESULTS: A total of 110 participants (92%) and 109 participants (91%) agreed to attempt Fried's phenotype method and SPPB, respectively. No adverse events occurred during any assessments. According to Fried's phenotype method, the prevalence of frailty and pre-frailty was 35% and 56%, respectively, and according to the SPPB, the prevalence of frailty and pre-frailty was 50% and 35%, respectively. There was fair to moderate agreement between methods for determining which participants were frail (0.488 [0.082], p < 0.001) and pre-frail (0.272 [0.084], p = 0.002). CONCLUSIONS: Frailty and pre-frailty are common in this geriatric outpatient population, and there is fair to moderate agreement between Fried's phenotype method and the SPPB. Over 90% of the patients who were eligible for the study agreed to attempt the frailty assessments, demonstrating that according to our feasibility criteria, frailty can be assessed in this patient population. Assessing frailty may help clinicians identify high-risk patients and tailor interventions based on baseline frailty characteristics.

Comparative trends in incident fracture rates for all long-term care and community-dwelling seniors in Ontario, Canada, 2002-2012.

SUMMARY: In this population-based study, we compared incident fracture rates in long-term care (LTC) versus community seniors between 2002 and 2012. Hip fracture rates declined more rapidly in LTC than in the community. An excess burden of fractures occurred in LTC for hip, pelvis, and humerus fractures in men and hip fractures only in women. INTRODUCTION: This study compares trends in incident fracture rates between long-term care (LTC) and community-dwelling seniors ≥65 years, 2002-2012. METHODS: This is a population-based cohort study using administrative data. Measurements were age/sex-adjusted incident fracture rates and rate ratios (RR) and annual percent change (APC). RESULTS: Over 11 years, hip fracture rates had a marked decline occurring more rapidly in LTC (APC, -3.49 (95% confidence interval (CI), -3.97, -3.01)) compared with the community (APC, -2.93 (95% CI, -3.28, -2.57); p < 0.05 for difference in slopes). Humerus and wrist fracture rates decreased; however, an opposite trend occurred for pelvis and spine fractures with rates increasing over time in both cohorts (all APCs, p < 0.05). In 2012, incident hip fracture rates were higher in LTC than the community (RRs: women, 1.55 (95% CI, 1.45, 1.67); men, 2.18 (95% CI, 1.93, 2.47)). Higher rates of pelvis (RR, 1.48 (95% CI, 1.22, 1.80)) and humerus (RR, 1.40 (95% CI, 1.07, 1.84)) fractures were observed in LTC men, not women. In women, wrist (RR, 0.76 (95% CI, 0.71, 0.81)) and spine (RR, 0.52 (95% CI, 0.45, 0.61)) fracture rates were lower in LTC than the community; in men, spine (RR, 0.75 (95% CI, 0.57, 0.98) but not wrist fracture (RR, 0.91 (95% CI, 0.67, 1.23)) rates were significantly lower in LTC than the community. CONCLUSION: Previous studies in the community have shown declining hip fracture rates over time, also demonstrated in our study but at a more rapid rate in LTC. Rates of humerus and wrist fractures also declined. An excess burden of fractures in LTC occurred for hip fractures in women and for hip, pelvis, and humerus fractures in men.

Cytomegalovirus disease is associated with higher all-cause mortality after lung transplantation despite extended antiviral prophylaxis.

BACKGROUND: The duration of anticytomegalovirus (CMV) prophylaxis after lung transplantation (LT) varies among transplant centers. METHODS: A retrospective review of CMV donor-seropositive/recipient-seronegative (D+/R-) and CMV recipient-seropositive (R+) LT patients between January 2005 and September 2012 was performed. Starting January 2007, valganciclovir prophylaxis was given for at least 12 months (often lifelong) for CMV D+/R- and extended from three to six months for R+ LT patients. Risks of CMV infection and CMV disease, and mortality after LT, were assessed. RESULTS: A total of 88 LT patients were studied, including 32 CMV D+/R-, and 56 R+ patients. During the follow-up period, 11 (12.5%) patients had asymptomatic CMV infection, and nine (10.3%) developed CMV disease. CMV disease (HR, 4.189; 95% CI: 1.672-10.495; p = 0.002) and CMV infection and disease (HR, 3.775; 95% CI: 1.729-8.240; p = 0.001) were significant risk factors for mortality. Overall, no significant difference was observed in rates of CMV infection or disease among LT recipients who received shorter vs. extended CMV prophylaxis. CONCLUSIONS: Despite extended prophylaxis, LT patients remain at risk of CMV infection and disease. CMV remains associated with increased mortality after transplantation.

A Frailty Index predicts 10-year fracture risk in adults age 25 years and older: results from the Canadian Multicentre Osteoporosis Study (CaMos).

UNLABELLED: We created a 30-item Frailty Index in the Canadian Multicentre Osteoporosis Study. A Frailty Index is a sensitive measure that can quantify fracture risk according to degree of frailty. Our results indicated that at any age, frailty was an important independent risk factor for fracture over 10 years. INTRODUCTION: In later life, frailty has been linked to fractures. It is likely that the antecedents of fracture are seen across the life course, in ways not entirely captured by traditional osteoporosis risk factors. Using data collected from the prospective, population-based Canadian Multicentre Osteoporosis Study (CaMos), we created the 30-item CaMos Frailty Index and examined whether it was associated with incident fractures over 10 years. METHODS: All CaMos participants aged 25 years and older (n = 9,423) were included in the analysis. To examine the relationship between baseline Frailty Index scores and incident fractures, a competing risk proportional sub-distribution hazards model was used with death considered a competing risk. Analyses were adjusted for age, sex, body mass index, education level, femoral neck T-score, and antiresorptive therapy. RESULTS: At baseline, the mean age was 62.1 years [standard deviation (SD) 13.4], and 69.4 % were women. The mean Frailty Index score was 0.13 (SD 0.11), ranging from 0 to 0.66. For every 0.10 increase in Frailty Index scores (approximately one SD), the hazard ratio was 1.25 (p < 0.001) for all fractures, 1.18 (p = 0.043) for hip fractures, and 1.30 (p ≤ 0.001) for clinical vertebral fractures. CONCLUSION: The CaMos Frailty Index quantified fracture risk according to degree of frailty. Irrespective of age and bone mineral density, the Frailty Index was associated with hip, vertebral, and all-type clinical fractures. Predicting late onset illnesses may have to consider overall health status and not just traditional risk factors.

Leg weakness in a lung transplant patient.

Progressive multifocal leukoencephalopathy (PML) is associated with JC polyomavirus (JCV) infection of central nervous system oligodendrocytes resulting in demyelinization and progressive focal neurologic deficits. Reactivation of dormant JCV occurs in the setting of immunosuppression, most commonly in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) or hematological malignancies. PML has also been reported in solid organ transplant recipients. We report the case of a 61-year-old man after bilateral lung transplantation for chronic hypersensitivity pneumonitis who presented with leg weakness, cognitive decline, and expressive aphasia at 5 months post transplantation. Magnetic resonance imaging and brain biopsy were consistent with PML. Treatment attempt with cytarabine was unsuccessful, and immunomodulation resulted in recurrent grade A3 rejection. The difficulty of managing PML in lung transplant patients is highlighted by the lack of directed therapy and risk of graft rejection or failure with attempts at decreasing immunosuppression.

Treating osteoporosis in Canada: what clinical efficacy data should be considered by policy decision makers?

UNLABELLED: SAUMMARY: Using a Markov state-transition model, we estimated fractures averted with risedronate using two different types of clinical efficacy data. Summary data, as opposed to individual patient data (IPD), underestimated the number of fractures averted when applied in a specified high risk population. The choice of clinical efficacy data is an important consideration in health economic models evaluating osteoporosis therapies. INTRODUCTION: This paper contrasts fracture reduction estimates for risedronate utilizing efficacy data from two approaches to meta-analysis: summary data versus individual patient data. We also examined differences in fracture reduction explained by varied cohort selection, especially the inclusion of low- versus high-risk populations. METHODS: Using a Markov state-transition model, we compared fractures averted over 3 years in a hypothetical cohort by inputting fracture risk reduction estimates (risedronate versus placebo) from two data sources (summary data versus IPD). The cohort consisted of 100,000 Canadian women, age > or =65 years with osteoporosis (WHO criteria T-score < or = -2.5) and prevalent morphometric vertebral fracture. RESULTS: Non-vertebral fractures averted with risedronate were: 3,571 and 6,584 per 100,000 women for summary data and IPD, respectively. For vertebral fractures, the numbers were 8,552 and 10,127. When IPD versus summary data was used, an additional 3,013 more non-vertebral fractures and 1,575 vertebral fractures were averted. DISCUSSION: Relative risk estimates from IPD analyses were the best choice for modelling fracture outcomes when applied in a specified high-risk population. In addition to superior statistical methodology, they utilized RCT cohorts that are more representative of higher risk patients requiring treatment (osteoporotic women > or =65 years with a prevalent vertebral fracture).

Risk factors for low BMD in healthy men age 50 years or older: a systematic review.

SUMMARY: In this systematic review, we summarize risk factors for low bone mineral density and bone loss in healthy men age 50 years or older. Consistent risk factors were: age, smoking, low weight, physical/functional limitations, and previous fracture. Data specific to men has clinical and policy implications. INTRODUCTION: Osteoporosis is a significant health care problem in men as well as women, yet the majority of evidence on diagnosis and management of osteoporosis is focused on postmenopausal women. The objective of this systematic review is to examine risk factors for low bone mineral density (BMD) and bone loss in healthy men age 50 years or older. MATERIALS AND METHODS: A systematic search for observational studies was conducted in MEDLINE, Cochrane Database of Systematic Reviews, DARE, CENTRAL, CINAHL and Embase, Health STAR. The three main search concepts were bone density, densitometry, and risk factors. Trained reviewers assessed articles using a priori criteria. RESULTS: Of 642 screened abstracts, 299 articles required a full review, and 25 remained in the final assessment. Consistent risk factors for low BMD/bone loss were: advancing age, smoking, and low weight/weight loss. Although less evidence was available, physical/functional limitations and prevalent fracture (after age 50) were also associated with low BMD/bone loss. The evidence was inconsistent or weak for physical activity, alcohol consumption, calcium intake, muscle strength, family history of fracture/osteoporosis, and height/height loss. CONCLUSION: In this systematic review, we identified several risk factors for low BMD/bone loss in men that are measurable in primary practice.

The impact of incident fractures on health-related quality of life: 5 years of data from the Canadian Multicentre Osteoporosis Study.

UNLABELLED: Using prospective data from the Canadian Multicentre Osteoporosis Study (CaMos), we compared health utilities index (HUI) scores after 5 years of follow-up among participants (50 years and older) with and without incident clinical fractures. Incident fractures had a negative impact on HUI scores over time. INTRODUCTION: This study examined change in health-related quality of life (HRQL) in those with and without incident clinical fractures as measured by the HUI. METHODS: The study cohort was 4,820 women and 1,783 men (50 years and older) from the CaMos. The HUI was administered at baseline and year 5. Participants were sub-divided into incident fracture groups (hip, rib, spine, forearm, pelvis, other) and were compared with those without these fractures. The effects of both time and fracture type on HUI scores were examined in multivariable regression analyses. RESULTS: Men and women with hip fractures, compared to those without, had lower HUI measures that ranged from -0.05 to -0.25. Both women and men with spine fractures had significant deficits on the pain attributes (-0.07 to -0.12). In women, self-care (-0.06), mobility and ambulation (-0.05) were also negatively impacted. Women with rib fractures had deficits similar to women with spine fractures, and these effects persisted over time. In men, rib fractures did not significantly affect HUI scores. Pelvic and forearm fractures did not substantially influence HUI scores. CONCLUSION: The HUI was a sensitive measure of HRQL change over time. These results will inform economic analyses evaluating osteoporosis therapies.

The osteoporosis care gap in men with fragility fractures: the Canadian Multicentre Osteoporosis Study.

UNLABELLED: We examined osteoporosis diagnosis/treatment in 2,187 community dwelling men age 50+. After five years in the study, 90% of men with fragility fractures remained undiagnosed and untreated for osteoporosis. The need to treat fragility fractures is well established in guidelines, and these numbers represent an important care gap. INTRODUCTION: Whether physicians in the community are recognizing and appropriately treating osteoporosis and fragility fractures in men remains unknown. We examined the rate of diagnosis and treatment in community dwelling men participating in the Canadian Multicentre Osteoporosis Study (CaMos). METHODS: Between February 1996 and September 2002, 2,187 participants were recruited from nine sites across Canada and prospectively followed. Information on osteoporosis diagnosis, fractures, medications were collected annually by a detailed questionnaire. DXA examination of lumbar spine (L1-4) and hip were conducted at baseline and year five. RESULTS: Diagnosis and treatment in men with clinical fragility fractures was low: at baseline and year five only 2.3% and 10.3% of men with a clinical fracture reported an osteoporosis diagnosis, respectively. At year five, 90% of men with a clinical fragility fracture were untreated. Hip fractures were the most commonly treated (37.5% by year five). A diagnosis of osteoporosis resulted in greater treatment: 67% of participants with diagnosed osteoporosis were treated with a bisphosphonate and 87% were taking calcium and/or vitamin D (year five). CONCLUSIONS: In this population-based study, both a diagnostic and therapeutic gap existed between knowledge and practice related to fragility fractures and osteoporosis in men aged >or=50 years.

Localization of the exonuclease and polymerase domains of Bacillus subtilis DNA polymerase III.

Structural gene mutants were cloned and exploited to identify the major catalytic domains of Bacillus subtilis DNA polymerase III (BsPolIII), a 162.4-kDa [1437 amino acids (aa)] polymerase: 3'-5' exonuclease (Exo) required for replicative DNA synthesis. Analysis of the sequence, mutagenicity, and catalytic behavior of natural and site-directed point mutants of BsPolIII unequivocally located the domain involved in exonuclease catalysis within a 155-aa residue segment displaying homology with the Exo domain of Escherichia coli DNA polymerase I. Sequence analysis of four structural gene mutations which specifically alter then enzyme's reactivity to the inhibitory dGTP analog, 6-(p-hydroxyphenylhydrazino)uracil, and the inhibitory arabinonucleotide, araCTP, defined a domain (Pol) involved in dNTP binding. The Pol domain was in the C-terminal fourth of the enzyme within a 98-aa segment spanning aa 1175-1273. The primary structure of the domain was unique, displaying no obvious conservation in any other DNA polymerase, including the distantly related PolIIIs of the Gram- organisms, E. coli and Salmonella typhimurium.

Infectious mononucleosis in the older patient.

Six cases of infectious mononucleosis in patients more than 60 years old were reviewed. The geriatric patient with infectious mononucleosis often presents with nonspecific constitutional symptoms, without exudative pharyngitis. The disease may present as fever of obscure origin or mimic chronic lymphocytic leukemia in this age group. Diagnosis is established through characteristic findings on hematologic and serologic studies.

One-year graduated exercise program for men with angina pectoris. Evaluation by physiologic studies and coronary arteriography.

Eight men, 45 to 50 years of age, with mild stable angina pectoris, participated in a graduated exercise program. Coronary arteriography, left ventriculography, left ventricular hemodynamics at rest and during supine leg exercise, treadmill testing with electrocardiographic monitoring, and measurement of oxygen uptake were obtained before and 1 year after the exercise training program. No change was noted in the arteriographic appearance of coronary artery lesions or of collateral circulation. Left ventricular performance, assessed by qualitative left ventriculography and the hemodynamic response of the left ventricle to supine leg exercise, was unchanged after the training program. Oxygen consumption for a given repetitive work load during treadmill exercise decreased. Two patients with a pretraining exercise ECG positive for ischemia reverted to a normal response after the exercise program. All had a decrease in angina, an increase in self-esteem, and a more positive attitude toward their work and their disability.

Haemoglobin Belfast 15 (A12) tryptophan leading to arginine: a new unstable haemoglobin variant.

A new unstable haemoglobin, alpha(2)beta(2)15 Trp--> Arg (Hb Belfast), with increased oxygen affinity has been found during the routine investigation of a long-stay psychiatric patient. It seemed to cause little haematological disorder. The reticulocytes synthesized normal and abnormal beta-chains at the same rate but in the circulating blood Hb Belfast amounted to only 27.5% of the total haemoglobin.