Comparative performance of current definitions of sarcopenia against the prospective incidence of falls among community-dwelling seniors age 65 and older.

UNLABELLED: In this study, we compare the extent to which seven available definitions of sarcopenia and two related definitions predict the rate of falling. Our results suggest that the definitions of Baumgartner and Cruz-Jentoft best predict the rate of falls among sarcopenic versus non-sarcopenic community-dwelling seniors. INTRODUCTION: The purpose of the study is to compare the extent to which seven available definitions of sarcopenia and two related definitions predict the prospective rate of falling. METHODS: We studied a cohort of 445 seniors (mean age 71 years, 45 % men) living in the community who were followed with a detailed fall assessment for 3 years. For comparing the rate of falls in sarcopenic versus non-sarcopenic individuals, we used multivariate Poisson regression analyses adjusting for gender and treatment (original intervention tested vitamin D plus calcium against placebo). Of the seven available definitions, three were based on low lean mass alone (Baumgartner, Delmonico 1 and 2) and four required both low muscle mass and decreased performance in a functional test (Fielding, Cruz-Jentoft, Morley, Muscaritoli). The two related definitions were based on low lean mass alone (Studenski 1) and low lean mass contributing to weakness (Studenski 2). RESULTS: Among 445 participants, 231 fell, sustaining 514 falls over the 3-year follow-up. The prospective rate of falls in sarcopenic versus non-sarcopenic individuals was best predicted by the Baumgartner definition based on low lean mass alone (RR = 1.54; 95 % CI 1.09-2.18) with 11 % prevalence of sarcopenia and the Cruz-Jentoft definition based on low lean mass plus decreased functional performance (RR = 1.82; 95 % CI 1.24-2.69) with 7.1 % prevalence of sarcopenia. Consistently, fall rate was non-significantly higher in sarcopenic versus non-sarcopenic individuals based on the definitions of Delmonico 1, Fielding, and Morley. CONCLUSION: Among the definitions investigated, the Baumgartner definition and the Cruz-Jentoft definition had the highest validity for predicting the rate of falls.

Using a Claims-Based Frailty Index to Investigate Frailty, Survival, and Healthcare Expenditures among Older Adults Hospitalized for COVID-19 at an Academic Medical Center.

BACKGROUND: Frailty is associated with mortality in older adults hospitalized with COVID-19, yet few studies have quantified healthcare utilization and spending following COVID-19 hospitalization. OBJECTIVE: To evaluate whether survival and follow-up healthcare utilization and expenditures varied as a function of claims-based frailty status for older adults hospitalized with COVID-19. DESIGN: Retrospective cohort study. PARTICIPANTS: 136 patients aged 65 and older enrolled in an Accountable Care Organization (ACO) risk contract at an academic medical center and hospitalized for COVID-19 between March 11, 2020 - June 3, 2020. MEASUREMENTS: We linked a COVID-19 Registry with administrative claims data to quantify a frailty index and its relationship to mortality, healthcare utilization, and expenditures over 6 months following hospital discharge. Kaplan Meier curves and Cox Proportional Hazards models were used to evaluate survival by frailty. Kruskal-Wallis tests were used to compare utilization. A generalized linear model with a gamma distribution was used to evaluate differences in monthly Medicare expenditures. RESULTS: Much of the cohort was classified as moderate to severely frail (65.4%), 24.3% mildly frail, and 10.3% robust or pre-frail. Overall, 27.2% (n=37) of the cohort died (n=26 during hospitalization, n=11 after discharge) and survival did not significantly differ by frailty. Among survivors, inpatient hospitalizations during the 6-month follow-up period varied significantly by frailty (p=0.02). Mean cost over follow-up was $856.37 for the mild and $4914.16 for the moderate to severe frailty group, and monthly expenditures increased with higher frailty classification (p <.001). CONCLUSIONS: In this cohort, claims-based frailty was not significantly associated with survival but was associated with follow-up hospitalizations and Medicare expenditures.

Reproductive axis suppression in acute illness is related to disease severity.

Changes in the adrenal and thyroid axes in critically ill patients are accentuated by increasing disease severity. However, the relationship of gonadal axis suppression to severity of illness is not well defined. We evaluated serial serum levels of LH, FSH, and testosterone (T) in 59 men and 42 postmenopausal women admitted to critical care units with a spectrum of disease severity. Patients were grouped according to severity of illness by the Acute Physiologic and Chronic Health Evaluation II (APACHE II) scores and by survival. Patients with surgery, renal or hepatic failure, alcohol abuse, endocrine disease, or head trauma were excluded to avoid these confounding factors. In men, mean admission serum T levels in all groups were lower than in healthy controls (P < 0.005). In addition, T levels in men with severe illness (APACHE > 15) were lower than in men with relatively mild (APACHE < 10; P < 0.01) or moderate illness (APACHE 10-15; P < 0.05). These differences were accentuated as hospitalization progressed. In postmenopausal women and men, nadir serum FSH but not LH levels during hospitalization were lower in patients with APACHE greater than 15 than in patients with APACHE scores of 10-15 or less than 15 (P < 0.05). Grouping patients by survival yielded similar results. Analysis of drug effects, age, and PRL did not explain these relationships. We conclude that the degree of both central and peripheral suppression of the reproductive axis in acute illness is related to disease severity. This suppression could not be attributed to other factors known to alter the reproductive axis independently from critical illness (e.g. age, drugs, head trauma, hepatic failure, etc.). These findings further document a general endocrine response to acute illness involving several axes which is graded according to disease severity.

Both hyper- and hypogonadotropic hypogonadism occur transiently in acute illness: bio- and immunoactive gonadotropins.

Previous reports of hypogonadotropic hypogonadism in critically ill men may not reflect the complexity of changes in the hypothalamic-pituitary-gonadal (HPG) axis during acute illness. We sampled blood throughout hospitalization in 55 men admitted to acute care units to delineate the spectrum of changes in circulating gonadotropin and sex steroid levels at the onset and during recovery from acute illness. Bioactive LH and FSH were measured in a subset of patients. Percent free testosterone was measured to assess changes in binding to sex hormone binding globulin. Medications and serum estrogen and prolactin levels were monitored as potential causes of hypogonadotropism. Sustained suppression of serum testosterone levels below the normal range occurred in 62% of men with varying diagnoses and disease severity. Percent free testosterone remained constant. Hypogonadotropism was observed in most men (60%) and occurred independently from head injury, surgery, medications, or hyperprolactinemia. In a subset of men (n = 16), LH and/or FSH rose transiently above the normal range. Bioactivity of both LH and FSH remained constant while serum testosterone levels decreased. In contrast to serum testosterone levels, mean serum levels of E1, E2 and androstenedione were not less than control values. We conclude that both primary and secondary hypogonadism occur transiently in acutely ill men and cannot be explained solely by medications, hyperprolactinemia, or hyperestrogenemia. Neither biopotency of gonadotropins nor binding of testosterone to SHBG change across the course of acute illness. The hypogonadism, often severe and prolonged, may contribute to the persistent catabolic state observed in many critically ill patients.

Association between protein intake and 1-y weight and height gains in Bangladeshi children aged 3-11 y.

We examined 1-y weight and height gains among 238 rural Bangladeshi children aged 3-11 y old to address the hypothesis that dietary protein composition is associated with growth velocity. Energy-adjusted total protein and energy-adjusted protein from sources other than cereal (animal, pulses, and vegetables) were associated with higher weight gains, after adjustment for age, sex, land ownership, diarrhea, acute respiratory infections, other fevers, nutritional status at the beginning of the study, and average body mass index of the mother [daily intake of energy-adjusted noncereal protein (beta +/- SE): 14.2 +/- 6.4 g.y-1.g-1, P = 0.03; total protein: 13.1 +/- 6.3 g.y-1.g-1, P = 0.04; and protein as percent of energy intake: 39.5 +/- 20.2 g.y-1.% of energy from protein-1, P = 0.05]. These findings are compatible with the hypotheses that protein intake may be a limiting factor for weight gain in this population, or that higher protein intake from animal sources (mostly fish) and legumes (lentils and peas) may be accompanied by higher intakes of limiting micronutrients.

Serial neuropsychological assessment and magnetic resonance imaging analysis in multiple sclerosis.

OBJECTIVE: To assess the correlation between cognitive dysfunction and disease burden in multiple sclerosis (MS) during a 1-year period. DESIGN: The Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis was performed at entrance and 1 year. Patients underwent at least 20 proton density (range, 20-24) and T2-weighted axial magnetic resonance imaging (MRI) brain scans except for stable patients who were scanned monthly. Magnetic resonance imaging was evaluated using computer-automated, 3-dimensional volumetric analysis. SETTING: A research clinic of a university hospital. PATIENTS: Forty-four patients with MS of the following disease categories: relapsing-remitting (14), relapsing-remitting progressive (12), chronic progressive (13), and stable (5). MAIN OUTCOME MEASURES: The relationships between scores on the Brief, Repeatable Battery of Neuropsychological Tests in Multiple Sclerosis and 2 MRI measures (total lesion volume and brain to intracranial cavity volume ratio) were assessed using linear regression. These MRI measures were also compared with cognitive status at 1 year using analysis of variance. RESULTS: Overall, there was no decline in mean cognitive test performance during 1 year. Significant correlations were found between baseline neuropsychological test scores of nonverbal memory, information-processing speed, and attention and both MRI measures. Patients with chronic progressive MS demonstrated the strongest correlations. At 1 year, change in information-processing speed and attention correlated with change in total lesion volume. The mean increase in total lesion volume was 5.7 mL for 4 patients whose cognitive status worsened compared with 0.4 mL for 19 patients who improved and 0.5 mL for 21 patients who remained stable. CONCLUSIONS: During a 1-year period mean cognitive performance did not worsen. Automated volumetric MRI measures of total lesion volume and brain to intracranial cavity volume ratio correlated with neuropsychological performance, especially in patients with chronic progressive MS. Worsening MRI lesion burden correlated with cognitive decline.

Hypomanic reactions to ACTH and prednisone treatment for multiple sclerosis.

Nine of 50 MS patients became hypomanic or manic during treatment with ACTH or prednisone. Symptoms did not occur with every drug exposure and were more common with ACTH. Patients at risk were identified by episodes of major depression before and after the onset of MS and by family histories of depression or alcoholism.

Immunosuppression with high-dose i.v. cyclophosphamide and ACTH in progressive multiple sclerosis: cumulative 6-year experience in 164 patients.

One hundred sixty-four patients with chronic progressive multiple sclerosis (MS) have been treated with a regimen of high-dose IV cyclophosphamide and ACTH over the past 6 years. Their status was reviewed to determine complications associated with treatment, dosage of medication used to induce a remission, factors which may predict a response to therapy, and subsequent course following treatment. One year following initial treatment, 81% of patients were improved or stabilized. Reprogression occurred in 69% of patients at a mean time of 17.6 months. Fifty-eight patients who initially stabilized after treatment and then reprogressed were treated a second time. One year after retreatment, 70% of these patients were improved or stabilized. Alopecia, nausea and vomiting, and minor infections were the most frequent complications. There were no deaths associated with treatment, the complication rate did not change with multiple treatments, and no late complications have yet been observed. Improvement tended to occur in younger patients with shorter disease duration. Although this treatment regimen is generally well tolerated and can favorably affect the course of chronic progressive MS in a majority of patients, a single treatment does not induce a permanent remission, and some form of maintenance treatment or retreatment is required. Current treatment programs involve testing a modified induction regimen and periodic outpatient booster injections to maintain remission.

Immunologic effects of cyclophosphamide/ACTH in patients with chronic progressive multiple sclerosis.

We examined immune function and changes in T cell populations over a 1-year period in a series of progressive multiple sclerosis (MS) patients treated with different regimens of cyclophosphamide/ACTH as part of the Northeast Multiple Sclerosis Treatment Group. Our studies were designed to determine the effect of different cyclophosphamide/ACTH regimens on T cell populations and functional immune assays and to determine whether immune measures could be identified to predict which patients responded favorably to treatment. Cyclophosphamide/ACTH infusions significantly decreased the proportion of peripheral blood CD4+ T cells at 2, 6 and 12 months following treatment while there was a tendency for increased CD8 expression. This was associated with significant decreases of CD4/CD8 ratios at 2, 6 and 12 months following treatment compared to pretreatment. No changes in CD3+ T cells were observed while there were increased percentages of CDw26 (Ta1) positive and IL-2 positive T cells following treatment. The only T cell populations predictive of improvement were percentages of either CD3+ or CD4+ cells where increased percentages of either these populations at 2 months following cyclophosphamide/ACTH infusions were associated with improvement at both 6 and 12 months. In terms of functional immune measures, we found that cyclophosphamide/ACTH treatment decreased the level of proliferation in the allogeneic mixed lymphocyte reaction (MLR) at 2 months and of spontaneous proliferation of mononuclear cells at 12 months following therapy. Changes in spontaneous proliferation were predictive of clinical improvement at 12 months in that subjects with improved scores on the disability status scale (DSS) had decreases in spontaneous proliferation at 12 months as compared to pretreatment, whereas those stable or worse did not change significantly. Thus, our studies have demonstrated specific alterations in immune function following immunosuppression with cyclophosphamide/ACTH and suggest that certain immune measures may be linked to a positive clinical response and thus associated with disease progression in MS.

Hemoconcentration is an early marker for organ failure and necrotizing pancreatitis.

In a previous retrospective case-control study, hemoconcentration was associated with the development of pancreatic necrosis. The aim of the present study was to determine in a cohort study whether hemoconcentration is a marker for both organ failure and necrotizing pancreatitis. A cohort study was performed on patients admitted with acute pancreatitis from February 1996 to April 1997. Pancreatic necrosis was defined by findings on dynamic contrast-enhanced computed tomography scan or magnetic resonance imaging. Of 128 total patients with acute pancreatitis, 53 underwent computed tomography or magnetic resonance imaging. Eighteen of 53 had necrotizing pancreatitis. Logistic regression identified an admission hematocrit > or = 44% and a failure of admission hematocrit to decrease at 24 hours as the best binary predictors of necrotizing pancreatitis and organ failure. By 24 hours, 17 of 18 patients with necrotizing pancreatitis versus 11 of 35 with interstitial pancreatitis met one or the other criterion for necrosis (p < 0.001). By 24 hours, 13 of 15 with organ failure versus 36 of 104 without organ failure met one or the other criterion (p < 0.001). The negative predictive value by 24 hours was 96% for necrotizing pancreatitis and 97% for organ failure. Hemoconcentration with an admission hematocrit > or = 44% and/or failure of admission hematocrit to decrease at approximately 24 hours was associated with the development of necrotizing pancreatitis and organ failure. Patients who did not experience hemoconcentration were very unlikely to develop pancreatic necrosis or organ failure.

The reproducibility of the revised American Fertility Society classification of endometriosis.

OBJECTIVE: To assess the degree of intraobserver and interobserver variability in endometriosis staging using the revised American Fertility Society (AFS) classification of endometriosis. DESIGN: Videotapes of laparoscopies of 20 patients with endometriosis were each scored twice by five observers. SETTING: The reproductive endocrine unit of a tertiary care, university-affiliated hospital. SUBJECTS: Five subspecialty-certified reproductive endocrinologists. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Variability in assigned score was measured for each of the five components of the AFS classification, as well as total scores and stage of endometriosis. RESULTS: There was considerable variability in the scores assigned to each videotape, both by the same observer and by different observers. The grand total score, which ranged from 0 to 90, varied with an SD of 13.44 when a single patient was rated twice by the same observer and varied with an SD of 17.12 when a single patient was rated by two different observers. Among individual components of the score, the greatest variability occurred in endometriosis of the ovary and cul-de-sac obliteration, with less variability observed for peritoneum endometriosis and for ovarian and tubal adhesions. Comparison of intraobserver and interobserver scores resulted in a change in endometriosis stage in 38% and 52% of patients, respectively. There were statistically significant differences in mean endometriosis scores among the observers in four of the five anatomic categories examined. CONCLUSIONS: Intraobserver and interobserver variability was high for ovarian endometriosis and cul-de-sac subscores using the revised AFS classification of endometriosis.

The impact of group psychological interventions on distress in infertile women.

Infertile women express higher levels of distress than fertile women, with distress peaking between the 2nd and 3rd year. The purpose of this study was to determine whether group psychological interventions could prevent this surge. One hundred eighty-four women who had been trying to conceive between 1 and 2 years were randomized into either a cognitive-behavioral group, a support group, or a control group. All experimental participants attended a 10-session group program. Participants completed psychological questionnaires at intake and again at 6 and 12 months. Substantial attrition occurred, particularly in the control group. The cognitive-behavioral and support participants experienced significant psychological improvement at 6 and 12 months compared with the control participants, with the cognitive-behavioral participants experiencing the greatest positive change.

Depression in multiple sclerosis.

Standardized interview techniques, diagnostic criteria, and rating scales were used to assess 50 moderately disabled multiple sclerosis (MS) patients. Fifty-four percent met lifetime Research Diagnostic Criteria for major depression, with a significant increase in the rate from before to after the onset of MS symptoms. The MS patients were significantly more depressed than other medical patients described in the literature. Major depressions were associated with steroid-treated exacerbations and a history of major depression. Symptoms of depression may be easily confused with those of MS, resulting in inadequate diagnosis and treatment.

Sexual behaviors relevant to HIV transmission in a rural African population. How much can a KAP survey tell us?

KAP surveys have been proposed as a means to gather quantitative information on AIDS-related sexual behaviors, but the validity of survey results has not been tested. The validity of data gathered during a KAP survey in a rural district in Northern Uganda (N = 1486) was examined analyzing expected behavioral patterns, agreement of partner reports, and concordance of number of sexual contacts across gender. Patterns of sexual behavior and age trends are as expected. More men (50%) than women (18.5%) reported premarital sex. The likelihood of sexual intercourse before marriage increases with age at first marriage and with education. Women marry 5 years earlier than men, and the number of marriages increases with age. Peak incidence of casual sex occurs before age 25. The male/female ratio of casual sex is 4, as compared to about 3 in other African surveys. Single men are 2.5 times more likely to engage in casual sex than married males. Agreement of partner reports was examined for 392 couples selected by chance. 86% of the couples agreed on being polygamous or monogamous. On average men reported 1.3 (SD = 0.7) wives as compared to women reporting 1.5 (SD = 0.89) wives (P < 0.001). 16.8% of women declared more, and 2.8% less cowives than their husband (r = 0.65). Self-reports on frequency of sexual intercourse in the past month were examined for 256 monogamous couples. Mean frequencies differ (5.24 +/- 5.1 for men, 4.43 +/- 4.7 for women, P < 0.001). 42.8% of couples are in agreement within +/- 1 unit (r = 0.44). The total number of extra-marital and marital sex acts, as well as the total number of partners reported by each gender are similar. There is, however, a striking gender difference in reporting of casual partners in the past year. Data were found to be accurate at the aggregate level. However, accuracy of reporting at the individual level was found to be low. The gender difference in reporting of casual partners may be due to female underreporting, to not having captured prostitutes or to a different perception of the meaning of casual partnership. All KAP surveys should include a validity analysis, so as to provide a sense of the accuracy of the surveys and allow for comparison of the quality of different KAP surveys. There is an urgent need for a standardized approach to validating the findings from AIDS-related KAP surveys. Some of the indirect methods described here could be relevant for further use.

Complications of dual chamber pacemaker implantation in the elderly. Pacemaker Selection in the Elderly (PASE) Investigators.

Pacemakers are frequently implanted, yet accurate prospective data on implant complications are limited. Elderly patients may be at increased risk of implant complications and are increasingly being referred for pacemaker implantation. The purpose of the present analysis was to define the incidence and possible predictors of serious complications of dual chamber permanent pacemaker implantation in the elderly. Therefore, we sought to prospectively identify the incidence and predictors of pacemaker implant complications in a large multicenter trial involving patients receiving a dual chamber pacemaker. The Pacemaker Selection in the Elderly (PASE) study was a prospective trial designed to evaluate quality of life in dual chamber pacemaker recipients age 65 years or older randomized to DDDR versus VVIR programming. In addition to being age 65 years or older, patients enrolled in this study were in normal sinus rhythm, and had standard indications for permanent pacemaker implantation. All patients received dual chamber pacemakers and were randomized to DDDR versus VVIR pacing. Pacemaker implant complications were collected on standardized forms which were completed at pacemaker implantation and during follow-up appointments. In this study of 407 patients, there were 26 complications occurring in 25 patients (6.1%). The most frequent complication was lead dislodgment which occurred in 9 patients. This was followed by pneumothorax (8 patients) and cardiac perforations (4 patients). In 18 patients (4.4%) repeat surgical procedures (including chest tubes) were required. Complications were noted prior to discharge in only 18 patients. There were no significant predictors of overall complications. Pneumothorax was more frequent in patients > or = 75 years old, and was observed only in patients with subclavian venous access. In conclusion, complications from pacemaker implantation in the elderly are seen in 6.1% of patients and 4.4% of patients require a repeat surgical procedure. Other than advanced age and lower weight predicting for pneumothorax, there are no significant clinical predictors of complications.

Fall prevention with supplemental and active forms of vitamin D: a meta-analysis of randomised controlled trials.

OBJECTIVE: To test the efficacy of supplemental vitamin D and active forms of vitamin D with or without calcium in preventing falls among older individuals. DATA SOURCES: We searched Medline, the Cochrane central register of controlled trials, BIOSIS, and Embase up to August 2008 for relevant articles. Further studies were identified by consulting clinical experts, bibliographies, and abstracts. We contacted authors for additional data when necessary. Review methods Only double blind randomised controlled trials of older individuals (mean age 65 years or older) receiving a defined oral dose of supplemental vitamin D (vitamin D(3) (cholecalciferol) or vitamin D(2) (ergocalciferol)) or an active form of vitamin D (1alpha-hydroxyvitamin D(3) (1alpha-hydroxycalciferol) or 1,25-dihydroxyvitamin D(3) (1,25-dihydroxycholecalciferol)) and with sufficiently specified fall assessment were considered for inclusion. RESULTS: Eight randomised controlled trials (n=2426) of supplemental vitamin D met our inclusion criteria. Heterogeneity among trials was observed for dose of vitamin D (700-1000 IU/day v 200-600 IU/day; P=0.02) and achieved 25-hydroxyvitamin D(3) concentration (25(OH)D concentration: <60 nmol/l v >or=60 nmol/l; P=0.005). High dose supplemental vitamin D reduced fall risk by 19% (pooled relative risk (RR) 0.81, 95% CI 0.71 to 0.92; n=1921 from seven trials), whereas achieved serum 25(OH)D concentrations of 60 nmol/l or more resulted in a 23% fall reduction (pooled RR 0.77, 95% CI 0.65 to 0.90). Falls were not notably reduced by low dose supplemental vitamin D (pooled RR 1.10, 95% CI 0.89 to 1.35; n=505 from two trials) or by achieved serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l (pooled RR 1.35, 95% CI 0.98 to 1.84). Two randomised controlled trials (n=624) of active forms of vitamin D met our inclusion criteria. Active forms of vitamin D reduced fall risk by 22% (pooled RR 0.78, 95% CI 0.64 to 0.94). CONCLUSIONS: Supplemental vitamin D in a dose of 700-1000 IU a day reduced the risk of falling among older individuals by 19% and to a similar degree as active forms of vitamin D. Doses of supplemental vitamin D of less than 700 IU or serum 25-hydroxyvitamin D concentrations of less than 60 nmol/l may not reduce the risk of falling among older individuals.

Effect of seasonality and weather on fracture risk in individuals 65 years and older.

UNLABELLED: In this large population-based study, fracture rates for hips, distal forearms, proximal humeri, and ankles were higher in winter than in other seasons, although the winter peak was small for hip fractures (p < 0.05 at all sites). Younger age between 65 and 80, living in warmer states and male gender were associated with increased winter morbidity due to fractures. INTRODUCTION: The objective was to investigate seasonal variation in the incidence of four common fractures, and explore the association of weather with risk. METHODS: Population-based analysis of individuals age 65 and older, including fractures of the hip, the distal forearm, the proximal humerus and the ankle. Weather information was obtained from the US National Oceanic and Atmospheric Administration website. RESULTS: For all fractures, rates were highest in winter and lowest in summer (p < 0.05 at all sites). Winter peaks were more pronounced in warm climate states, in men, and in those younger than 80 years old. In winter, total snowfall was associated with a reduced risk of hip fracture (-5% per 20 inches) but an increased risk of non-hip fractures (6-12%; p < 0.05 at all sites). In summer, hip fracture risk tended to be lower during sunny weather (- 3% per 2 weeks of sunny days; p = 0.13), while other fractures were increased (15%-20%; p < 0.05) in sunny weather. CONCLUSION: Fractures contribute considerably to winter morbidity in older individuals. Younger age between 65 and 80, living in warmer states and male gender are risk factors for increased winter morbidity due to fractures. Weather affects hip fracture risk differently than the other fractures studied.

A randomized blinded trial of combination therapy with cyclophosphamide in patients-with active multiple sclerosis on interferon beta.

OBJECTIVE: To evaluate the efficacy and safety of combination therapy with pulse cyclophosphamide given with methylprednisolone (MP) and interferon beta (IFNbeta)-Ia in multiple sclerosis (MS) patients with active disease during IFNbeta monotherapy. METHODS: This was a randomized, single-blind, parallel-group, multicenter trial in MS patients with a history of active disease during IFNbeta treatment. Patients were randomized to either cyclophosphamide 800 mg/m2 plus methylprednisolone 1 g IV (CY/MP) or methylprednisolone once a month for six months and then followed for an additional 18 months. All patients received three days of methylprednisolone 1 g IV at screening and 30 mcg IFNbeta-Ia IM weekly for the entire 24 months. The primary endpoint was change from baseline in the mean number of gadolinium-enhancing (Gd+) lesions. Secondary clinical endpoints included time to treatment failure. RESULTS: Fifty-nine patients were randomized to treatment: 30 to CY/MP and 29 to MP Change from baseline in the number of Gd+ lesions was significantly different between treatment groups at three (P =0.01), six (P =0.04) and 12 months (P =0.02), with fewer lesions in the CY/MP group. The cumulative rate of treatment failure was significantly lower in the CY/MP group compared with the MP group (rate ratio =0.30; 95% confidence interval, 0.12-0.75; P =0.011). CY/MP treatment was well tolerated. CONCLUSION: Combination therapy with CY/MP and IFNbeta-Ia decreased the number of Gd+ lesions and slowed clinical activity in patients with previously active disease on IFNbeta alone.

The use of a simple Likert scale to measure quality of life in brain tumor patients.

The use of a self-administered 10-Point Likert self-assessment quality of life scale was explored in a convenience sample of patients attending a brain tumor clinic. The original scale, developed by Priestman, was modified to be more brain-tumor specific. A total of 430 patients completed the scale at 535 different points of measurement. The patients had a variety of brain tumors ranging from meningiomas to high-grade gliomas. The Total Score of the original scale and the Modified Total Score of the brain-specific version were explored in relationship to patient demographics and available clinical characteristics: age, gender, severity of tumor, location of tumor, survival rates, prior surgery, radiation, radiosurgery, and chemotherapy. We also examined the relationship between sub-scales and these variables. On a scale of 10-100, the average Total Score was 67.83, not significantly different from the Modified Score. There were no differences between bilateral, midline, or left- versus right-sided lesions. Patients with the worst prognosis in terms of tumor type were 5-6 points lower in quality of life than patients with intermediate or relatively good prognosis. In a multiple regression model, adjusted for age, the overall score was related only to tumor severity and to gender, with women having significantly poorer functional status than men by 4 points. Both the Modified and Total Scores were significantly associated with higher mortality risk, and more specifically, poor scores on well-being, mood, physical function, house/job performance, self-care, concentration, and energy all predicted higher mortality risk. We suggest that the simplicity of this instrument may make it particularly useful for longitudinal assessment of quality of life in brain tumor patients.