Staphylococcus aureus adhesion to the host.

Staphylococcus aureus is a pathobiont capable of colonizing and infecting most tissues within the human body, resulting in a multitude of different clinical outcomes. Adhesion of S. aureus to the host is crucial for both host colonization and the establishment of infections. Underlying the pathogen's success is a complex and diverse arsenal of adhesins. In this review, we discuss the different classes of adhesins, including a consideration of the various adhesion sites throughout the body and the clinical outcomes of each infection type. The development of therapeutics targeting the S. aureus host-pathogen interaction is a relatively understudied area. Due to the increasing global threat of antimicrobial resistance, it is crucial that innovative and alternative approaches are considered. Neutralizing virulence factors, through the development of antivirulence agents, could reduce bacterial pathogenicity and the ever-increasing burden of S. aureus infections. This review provides insight into potentially efficacious adhesion-associated targets for the development of novel decolonizing and antivirulence strategies.

Reported Weight Change in Older Adults and Presence of Frailty.

OBJECTIVE: A 5% change in weight is a significant predictor for frailty and obesity. We ascertained how self-reported weight change over the lifespan impacts rates of frailty in older adults. METHODS: We identified 4,984 subjects ≥60 years with body composition measures from the National Health and Nutrition Examination Survey. An adapted version of Fried's frailty criteria was used as the primary outcome. Self-reported weight was assessed at time current,1 and 10 years earlier and at age 25. Weight changes between each time point were categorized as ≥ 5%, ≤5% or neutral. Logistic regression assessed the impact of weight change on the outcome of frailty. RESULTS: Among 4,984 participants, 56.5% were female, mean age was 71.1 years, and mean BMI was 28.2kg/m2. A weight loss of ≥ 5% had a higher association with frailty compared to current weight, age 25 (OR 2.94 [1.72,5.02]), 10 years ago (OR 1.68 [1.05,2.69]), and 1 year ago (OR 1.55 [1.02,2.36]). Weight gain in the last year was associated with increased rate of frailty (1.59 [1.09,2.32]). CONCLUSION: There is an association between frailty and reported weight loss over time while only weight gain in the last year has an association with frailty.

Association of Obesity and Frailty in Older Adults: NHANES 1999-2004.

OBJECTIVES: Body composition changes with aging can increase rates of obesity, frailty and impact function. Measuring adiposity using body fat (%BF) or central adiposity using waist circumference (WC) have greater diagnostic accuracy than traditional measures such as body mass index (BMI). DESIGN: This is an observational study. SETTING: This study focused on older community-dwelling participants. PARTICIPANTS: We identified individuals age ≥ 60 years old using the 1999-2004 cross-sectional National Health and Nutrition Survey (NHANES). INTERVENTION: The primary analysis evaluated the association between frailty and %BF or WC. Frailty was the primary predictor (robust=referent) and %BF and WC were considered continuous outcomes. Multiple imputation analyses accounted for missing characteristics. MEASUREMENT: Dual energy x-ray absorptiometry was used to assess %BF and WC was objectively measured. Frailty was defined using an adapted version of Fried's criteria that was self-reported: (low BMI<18.5kg/m2; slow walking speed [<0.8m/s]; weakness [unable to lift 10lbs]; exhaustion [difficulty walking between rooms on same floor] and low physical activity [compared to others]). Robust, pre-frail and frail persons met zero, 1 or 2, and ≥3 criteria, respectively. RESULTS: Of the 4,984 participants, the mean age was 71.1±0.2 (SE) years and 56.5% were females. We classified 2,246 (50.4%), 2,195 (40.3%), and 541 (9.2%) individuals as robust, pre-frail and frail, respectively. Percent BF was 35.9±0.13, 38.3±0.20 and 40.0±0.46 in the robust, pre-frail and frail individuals, respectively. WC was 99.5±0.32 in the robust, 100.1±0.43 in pre-frail, 104.7±1.17 in frail individuals. Compared to robust individuals, only frail individuals had greater %BF on average (ß=0.97±0.43,p=0.03); however, pre-frail and frail individuals had 2.18 and 4.80 greater WC, respectively (ß=2.18±0.64,p=0.002, and ß=4.80±1.1,p<0.001). CONCLUSION: Our results demonstrate that in older adults, frailty and pre-frailty are associated with a greater likelihood of high WC (as dichotomized) and a greater average WC (continuous).

Depression and Handgrip Strength Among U.S. Adults Aged 60 Years and Older from NHANES 2011-2014.

OBJECTIVES: Sarcopenia is a gradual loss of muscle mass and strength that occurs with aging. This muscle deterioration is linked to increased morbidity, disability, and other adverse outcomes. Although reduced handgrip strength can be considered a marker of sarcopenia and other aging-related decline in the elderly, there is limited research on this physical health problem in at-risk groups with common biopsychosocial conditions such as depression. Our primary objective was to ascertain level of combined handgrip strength and its relationship with depression among adults aged 60 years and older. DESIGN: Unadjusted and adjusted linear regression models were conducted with a cross-sectional survey dataset. SETTING: Secondary dataset from the 2011-2014 National Health and Nutrition Examination Survey (NHANES). PARTICIPANTS: Community-dwelling, non-institutionalized adults ≥60 years old (n=3,421). MEASUREMENTS: The predictor variables included a positive screen for clinically relevant depression (referent=PHQ-9 score <10). The criterion variable of combined handgrip strength (kg) was determined using a dynamometer. RESULTS: Mean age and BMI were 69.9 years (51.5% female) and 28.8 kg/m2, respectively. Mean combined handgrip strength in the overall cohort was 73.5 and 46.6 kg in males and females, respectively. Three hundred thirty-six (9.8%) reported symptoms of depression. In unadjusted and fully adjusted models, depression was significantly associated with reduced handgrip strength (B = -0.26±0.79 and B = -0.19±0.08, respectively; p<0.001). CONCLUSION: Our findings demonstrate handgrip strength has a significant inverse association with depression. Future longitudinal studies should investigate the causal processes and potential moderators and mediators of the relationships between depression and reduced handgrip strength. This information may further encourage the use of depression and handgrip strength assessments and aid in the monitoring and implementation of health care services that address both physical and mental health limitations among older adult populations.

Association of adiposity, telomere length and mortality: data from the NHANES 1999-2002.

BACKGROUND/OBJECTIVES: Telomere shortening is associated with age and risk of medical comorbidity. We assessed the relationship between measures of adiposity, leukocyte telomere length, and mortality and whether it is modified by age. SUBJECTS/METHODS: Subjects with dual-energy X-ray absorptiometry measures were identified using the National Health and Nutrition Examination Survey 1999-2002. Obesity was categorized using two body fat definitions (BF1%: men ⩾25%; females ⩾35%; BF2% ⩾28% and ⩾38%, respectively), body mass index (BMI) and waist circumference (WC; men ⩾102 cm; females ⩾88 cm). Telomere length relative to standard reference DNA (T/S ratio) was assessed using quantitative PCR. Weighted multivariable regression models evaluated the association of telomere length with adiposity, both continuously and categorically (low/normal BF%, low/high WC and standard BMI categories). Differences in telomere length by age and adiposity were ascertained and subsequent models were stratified by age. Proportional hazard models assessed the risk of mortality by adiposity status. A telomere by adiposity interaction was tested in the entire cohort and by age category (<60 vs ⩾60 years; <70 vs ⩾70 years). RESULTS: We identified 7827 subjects. Mean age was 46.1 years. Overall telomere length was 1.05±0.01 (s.e.) that differed by BF1% (low/high: 1.12±0.02 vs 1.03±0.02; P<0.001), BF2% (1.02±0.02 vs 1.11±0.02; P<0.001), BMI (underweight 1.08±0.03; normal 1.09±0.02; overweight 1.04±0.02; and obese 1.03±0.02;P<0.001) and WC (low/high 1.09±0.02 vs 1.02±0.02; P<0.001). Adjusted ß-coefficients evaluating the relationship between telomere length and adiposity (measured continuously) were as follows: BF1% (ß=-0.0033±0.0008; P<0.001), BF2% (-0.041±0.008; P<0.001), BMI (ß=-0.025±0.0008; P=0.005) and WC (ß=-0.0011±0.0004; P=0.007). High BF% (BF1%: ß=-0.035±0.011; P=0.002; BF2%: ß=-0.041±0.008; P<0.001) and WC (ß=-0.035±0.011; P=0.008) were inversely related to telomere length (TL). Stratifying by age, high BF1% (-0.061±0.013), BF2% (-0.065±0.01), BMI-obesity (-0.07±0.015) and high WC (-0.048±0.013) were significant (all P<0.001). This association diminished with increasing age. In older participants, TL was inversely related to mortality (hazard ratio 0.36 (0.27, 0.49)), as were those classified by BF1% (0.68 (0.56, 0.81)), BF2% (0.75 (0.65, 0.80)), BMI (0.50 (0.42, 0.60)) and WC (0.72 (0.63, 0.83)). No interaction was observed between adiposity status, telomere length and mortality. CONCLUSIONS: Obesity is associated with shorter telomere length in young participants, a relationship that diminishes with increasing age. It does not moderate the relationship with mortality.

Diagnostic accuracy of body mass index to identify obesity in older adults: NHANES 1999-2004.

BACKGROUND: Body composition changes with aging lead to increased adiposity and decreased muscle mass, making the diagnosis of obesity challenging. Conventional anthropometry, including body mass index (BMI), while easy to use clinically may misrepresent adiposity. We determined the diagnostic accuracy of BMI using dual-energy X-ray absorptiometry (DEXA) in assessing the degree of obesity in older adults. METHODS: The National Health and Nutrition Examination Surveys 1999-2004 were used to identify adults aged ⩾60 years with DEXA measures. They were categorized (yes/no) as having elevated body fat by gender (men: ⩾25%; women ⩾35%) and by BMI ⩾25 and ⩾30 kg m(-)(2). The diagnostic performance of BMI was assessed. Metabolic characteristics were compared in discordant cases of BMI/body fat. Weighting and analyses were performed per NHANES (National Health and Nutrition Examination Survey) guidelines. RESULTS: We identified 4984 subjects (men: 2453; women: 2531). Mean BMI and % body fat was 28.0 kg m(-2) and 30.8% in men, and 28.5 kg m(-)(2) and 42.1% in women. A BMI ⩾30 kg m(-)(2) had a low sensitivity and moderately high specificity (men: 32.9 and 80.8%, concordance index 0.66; women: 38.5 and 78.5%, concordance 0.69) correctly classifying 41.0 and 45.1% of obese subjects. A BMI ⩾25 kg m(-2) had a moderately high sensitivity and specificity (men: 80.7 and 99.6%, concordance 0.81; women: 76.9 and 98.8%, concordance 0.84) correctly classifying 80.8 and 78.5% of obese subjects. In subjects with BMI <30 kg m(-)(2), body fat was considered elevated in 67.1% and 61.5% of men and women, respectively. For a BMI ⩾30 kg m(-)(2), sensitivity drops from 40.3% to 14.5% and 44.5% to 23.4%, whereas specificity remains elevated (>98%), in men and women, respectively, in those 60-69.9 years to subjects aged ⩾80 years. Correct classification of obesity using a cutoff of 30 kg m(-)(2) drops from 48.1 to 23.9% and 49.0 to 19.6%, in men and women in these two age groups. CONCLUSIONS: Traditional measures poorly identify obesity in the elderly. In older adults, BMI may be a suboptimal marker for adiposity.

Oral bisphosphonates and upper gastrointestinal toxicity: a study of cancer and early signals of esophageal injury.

SUMMARY: We evaluated the association between bisphosphonate use and (1) upper gastrointestinal cancer, (2) upper endoscopy, (3) incident Barrett's esophagus, and (4) prescription antacid initiation among Medicare beneficiaries. We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. INTRODUCTION: Bisphosphonates can irritate the esophagus; a cancer association has been suggested. Widespread bisphosphonates use compels continued investigation of upper gastrointestinal toxicity. METHODS: Using a 40% Medicare random sample denominator, inpatient, outpatient (2003-2011), and prescription (2006-2011) claims, we studied patients age 68 and older with osteoporosis and/or oral bisphosphonate use. Inverse propensity weighting estimated marginal structural models for the effect of bisphosphonate intensity (pills per month) and cumulative bisphosphonate pills received on upper gastrointestinal cancer risk. Secondary analyses of sub-cohorts without past bisphosphonates or upper endoscopy assessed bisphosphonate initiation and risk of (1) upper endoscopy, (2) incident Barrett's esophagus, and (3) prescription antacid initiation. RESULTS: The cohort included 1.64 million beneficiaries: 87.9% women, mean age, 76.8 (standard deviation (SD) 9.3); mean follow-up, 39.6 months; 38.1% received oral bisphosphonates. Cumulative bisphosphonate receipt, among users, ranged from 4 to 252 pills (5th to 95th percentile). We identified 2,308 upper gastrointestinal cancers (0.43/1000 person years). We found no association between cumulative bisphosphonate pills and cancer, odds ratio (OR) for each additional pill 1.00 (95% confidence interval (CI) 1.00, 1.00). In sub-cohorts, compared to none, lowest cumulative bisphosphonate use (one to nine pills) was associated with higher risk of endoscopy (OR 1.11, 95% CI 1.08-1.14) and antacid initiation (OR 1.13, 95% CI 1.10-1.16); higher intensity conferred no increased risk. Higher intensity and higher cumulative bisphosphonate category were associated with lower Barrett's risk. CONCLUSIONS: We found no bisphosphonate-cancer association and negative bisphosphonate-Barrett's association. Bisphosphonate initiation appears to identify patients susceptible to early irritating effects; clinicians might offer alternatives and delay endoscopy or antacids.

Sarcopenia, sarcopenic obesity and mortality in older adults: results from the National Health and Nutrition Examination Survey III.

BACKGROUND: Sarcopenia is defined as the loss of skeletal muscle mass and quality, which accelerates with aging and is associated with functional decline. Rising obesity prevalence has led to a high-risk group with both disorders. We assessed mortality risk associated with sarcopenia and sarcopenic obesity in elders. METHODS: A subsample of 4652 subjects ≥60 years of age was identified from the National Health and Nutrition Examination Survey III (1988-1994), a cross-sectional survey of non-institutionalized adults. National Death Index data were linked to this data set. Sarcopenia was defined using a bioelectrical impedance formula validated using magnetic resonance imaging-measured skeletal mass by Janssen et al. Cutoffs for total skeletal muscle mass adjusted for height(2) were sex-specific (men: ≤5.75 kg/m(2); females ≤10.75 kg/m(2)). Obesity was based on % body fat (males: ≥27%, females: ≥38%). Modeling assessed mortality adjusting for age, sex, ethnicity (model 1), comorbidities (hypertension, diabetes, congestive heart failure, osteoporosis, cancer, coronary artery disease and arthritis), smoking, physical activity, self-reported health (model 2) and mobility limitations (model 3). RESULTS: Mean age was 70.6±0.2 years and 57.2% were female. Median follow-up was 14.3 years (interquartile range: 12.5-16.1). Overall prevalence of sarcopenia was 35.4% in women and 75.5% in men, which increased with age. Prevalence of obesity was 60.8% in women and 54.4% in men. Sarcopenic obesity prevalence was 18.1% in women and 42.9% in men. There were 2782 (61.7%) deaths, of which 39.0% were cardiovascular. Women with sarcopenia and sarcopenic obesity had a higher mortality risk than those without sarcopenia or obesity after adjustment (model 2, hazard ratio (HR): 1.35 (1.05-1.74) and 1.29 (1.03-1.60)). After adjusting for mobility limitations (model 3), sarcopenia alone (HR: 1.32 ((1.04-1.69) but not sarcopenia with obesity (HR: 1.25 (0.99-1.58)) was associated with mortality. For men, the risk of death with sarcopenia and sarcopenic obesity was nonsignificant in both model-2 (HR: 0.98 (0.77-1.25), and HR: 0.99 (0.79-1.23)) and model 3 (HR: 0.98 (0.77-1.24) and HR: 0.98 (0.79-1.22)). CONCLUSIONS: Older women with sarcopenia have an increased all-cause mortality risk independent of obesity.

Recent skin self-examination and doctor visits in relation to melanoma risk and tumour depth.

BACKGROUND: Little is known about the potential benefit of skin self-examination for melanoma prevention and early detection. OBJECTIVES: To determine whether skin self-examination is associated with reduced melanoma risk, self-detection of tumours, and reduced risk of deeper melanomas. METHODS: We used data from a population-based case-control study (423 cases, 678 controls) to assess recent skin self-examination in relation to self-detection, melanoma risk and tumour depth ( ≤1 mm; > 1 mm). Logistic regression was used to estimate odds ratios (ORs) and confidence intervals (CIs) for associations of interest. RESULTS: Skin self-examination conducted 1-11 times during a recent year was associated with a possible decrease in melanoma risk (OR 0·74; 95% CI 0·54-1·02). Melanoma risk was decreased for those who conducted skin self-examination and saw a doctor (OR 0·52; 95% CI 0·30-0·90). Among cases, those who examined their skin were twice as likely to self-detect the melanoma (OR 2·23; 95% CI 1·47-3·38), but self-detection was not associated with shallower tumours. Tumour depth was reduced for those who conducted skin self-examination 1-11 times during a recent year (OR 0·39; 95% CI 0·18-0·81), but was not influenced by seeing a doctor, or by conducting skin self-examination and seeing a doctor. CONCLUSIONS: Risk of a deeper tumour and possibly risk of melanoma were reduced by skin self-examination 1-11 times annually. Melanoma risk was markedly reduced by skin self-examination coupled with a doctor visit. We cannot, however, exclude the possibility that our findings reflect bias or confounding. Additional studies are needed to elucidate the potential benefits of skin self-examination for melanoma prevention and early detection.

Hearing loss and heavy metal toxicity in a Nicaraguan mining community: audiological results and case reports.

We measured fingernail metal levels, Békésy-type pure-tone thresholds and distortion product otoacoustic emission (DPOAE) levels in 59 subjects residing in the gold mining community of Bonanza, Nicaragua. Auditory testing revealed widespread hearing loss in the cohort. Nail metal concentrations (mercury, lead, aluminum, manganese and arsenic) far exceeded reference levels. No relationship was found between metal levels and auditory test results for the group as a whole. Statistically significant relationships were found between DPOAE response amplitudes and metal concentrations in a subgroup with less than 40 h per week of significant noise exposure; however, conclusions regarding these relationships should be tempered by the large number of analyses performed. Several young individuals with high metal levels reported neurological symptoms and had poor hearing. The data suggest that metal levels in artisanal mining communities present a significant public health problem and may affect hearing.

Neoadjuvant cetuximab, twice-weekly gemcitabine, and intensity-modulated radiotherapy (IMRT) in patients with pancreatic adenocarcinoma.

BACKGROUND: Neoadjuvant therapy has been investigated for localized and locally advanced pancreatic ductal adenocarcinoma (PDAC) but no standard of care exists. Combination cetuximab/gemcitabine/radiotherapy demonstrates encouraging preclinical activity in PDAC. We investigated cetuximab with twice-weekly gemcitabine and intensity-modulated radiotherapy (IMRT) as neoadjuvant therapy in patients with localized or locally advanced PDAC. EXPERIMENTAL DESIGN: Treatment consisted of cetuximab load at 400 mg/m(2) followed by cetuximab 250 mg/m(2) weekly and gemcitabine 50 mg/m(2) twice-weekly given concurrently with IMRT to 54 Gy. Following therapy, patients were considered for resection. RESULTS: Thirty-seven patients were enrolled with 33 assessable for response. Ten patients (30%) manifested partial response and 20 (61%) manifested stable disease by RECIST. Twenty-five patients (76%) underwent resection, including 18/23 previously borderline and 3/6 previously unresectable tumors. Twenty-three (92%) of these had negative surgical margins. Pathology revealed that 24% of resected tumors had grade III/IV tumor kill, including two pathological complete responses (8%). Median survival was 24.3 months in resected patients. Outcome did not vary by epidermal growth factor receptor status. CONCLUSIONS: Neoadjuvant therapy with cetuximab/gemcitabine/IMRT is tolerable and active in PDAC. Margin-negative resection rates are high and some locally advanced tumors can be downstaged to allow for complete resection with encouraging survival. Pathological complete responses can occur. This combination warrants further investigation.

Clinical trial: a randomized, study comparing meperidine (pethidine) and fentanyl in adult gastrointestinal endoscopy.

BACKGROUND: There is little evidence to guide choice between meperidine (pethidine) and fentanyl for sedation for gastrointestinal endoscopy. AIM: To compare meperidine with fentanyl in terms of procedure time and analgesia. METHODS: Single centre randomized controlled trial. Patients received narcotic doses and midazolam at the discretion of the attending endoscopist who was unaware of narcotic assignment. Endoscopy and recovery times were then recorded. The main outcome was total procedure time, defined as endoscopy time plus recovery time. Patient discomfort was assessed prior to discharge via visual analogue scale (VAS). RESULTS: In total, 55 patients were randomized to meperidine [44 colonoscopy and 11 esophagogastroduodenoscopy (EGD)] and 56 to fentanyl (45 colonoscopy and 11 EGD). Total procedure time was shorter for those receiving fentanyl (mean = 87.7 min) than for those receiving meperidine (mean = 102.9 min) (P = 0.05). The difference between the groups was explained by a shorter mean recovery time in the fentanyl group (63.0 min) than in the meperidine group (76.2 min) (P = 0.07). Based on post procedure pain scores, examinations with meperidine (mean = 1.99) were less painful when compared with those receiving fentanyl (mean = 2.86, P = 0.03). CONCLUSIONS: Fentanyl shortened total procedure time by reducing recovery time. A simple change in narcotic choice could increase endoscopy unit efficiency.

Continuous subcutaneous glucose monitoring in children with type 1 diabetes.

PURPOSE: To determine whether the use of continuous subcutaneous glucose monitoring will help in detecting unrecognized nocturnal hypoglycemia and in lowering hemoglobin A1c (HbA1c) levels (without increasing the risk for severe hypoglycemia) in children with type 1 diabetes. METHODS: Eleven children with type 1 diabetes and HbA1c values consistently >8.0% were randomized either to the Continuous Glucose Monitoring System (CGMS) group or to the control group. The CGMS group used 6 3-day sensors within a 30-day period. Both groups self-monitored their blood glucose levels a minimum of 4 times daily. HbA1c levels were measured at the start, at 1-month, and after 3 months of study. RESULTS: The 5 children using the CGMS had 17 asymptomatic episodes (85%) of glucose levels below 60 mg/dL (3.25 mmol/L) and 3 symptomatic episodes (15%) during the night in the study month. The 6 control children had 4 symptomatic nocturnal low episodes during the month. After the 30-day period of wearing the CGMS, the 5 children had a significantly lower mean HbA1c value compared with their initial value (mean +/- standard error of the mean [SEM] decrease =.36% +/-.07%). The mean decrease for the controls was.2% +/-.2%. After 3 months, 4 of the 5 children who used the CGMS continued to have lower HbA1c values in comparison to their initial values (mean +/- SEM decrease = 1.04% +/-.43%). Three of the 6 control participants also had lower HbA1c values at 3 months (mean +/- SEM decrease for the group =.62% +/-.44%). No severe hypoglycemic events occurred in either the CGMS or the control groups. CONCLUSION: In this pilot trial, continuous subcutaneous glucose monitoring was helpful in detecting asymptomatic nocturnal hypoglycemia as well as in lowering HbA1c values without increasing the risk for severe hypoglycemia in children with type 1 diabetes.

Impact of insulin lispro on HbA1c values in insulin pump users.

AIM: To compare the therapeutic efficacy of the short-acting insulin analogue insulin lispro (Humalog) with that of buffered regular human insulin (Velosulin) in patients on insulin pump therapy. PATIENTS AND METHODS: Sixty-two (45 women and 17 men) young patients with type 1 diabetes using insulin pump therapy were compared while using buffered regular human insulin for a mean +/- s.e.m. of 20.1+/-1.2 months or insulin lispro for a mean +/- s.e.m. of 19.7+/-0.5 months. The initial mean +/- s.e.m. age and duration of diabetes were 29.1+/-0.9 and 17.7+/-0.9 years, respectively. The mean HbA1c values, basal insulin dosages, premeal insulin dosages and number of low blood sugars were recorded during treatment with both insulins. RESULTS: Mean +/- s.e.m. HbA1c values were significantly lower (p < 0.001; paired Wilcoxon t-test) during insulin lispro treatment (7.4+/-0.1%) as compared to treatment with buffered regular human insulin (7.9+/-0.1%). Total units of insulin (mean +/- s.e.m.)/kg/day was significantly (p = 0.03) lower (0.61+/-0.02) during the insulin lispro treatment period as compared to the buffered regular human insulin treated period (0.65+/-0.03). Total mean +/- s.e.m. (U/kg/day) of basal insulin administered per day was higher when patients received insulin lispro treatment (0.44+/-0.02 vs. 0.42+/-0.01 for buffered regular human insulin treated period; p = 0.002). The premeal insulin boluses (mean +/- s.e.m.) for the two treatment groups were significantly different with less insulin required for the insulin lispro treatment period for all three meals (p < 0.001, t-test). The number of mild/moderate and severe hypoglycaemic episodes were similar in the two groups. CONCLUSION: We conclude that use of insulin lispro in pump therapy significantly lowers HbA1c values in comparison to therapy with buffered regular human insulin insulin without increasing hypoglycaemic episodes.

Determinants of health-related quality of life following elective total hip replacement.

This study examined the patient perspective of surgical success through the measurement of health-related quality of life (HRQOL), in order to identify the patient characteristics and process issues associated with postoperative changes in health status. Patients completed the RAND 36-item Health Survey 1.0 (SF-36) prior to surgery and at 6 months following surgery. Baseline patient demographic and clinical information were collected from the medical record and were used to develop models of change in HRQOL for 68 patients. While many patients improved, a number experienced no change or even a decline in HRQOL in the postoperative period. Factors associated with change in HRQOL are presented. The findings suggest that factors associated with change in health status can be systematically assessed, which may lead to the development of interventions aimed at those patient characteristics or process issues that impact on HRQOL.

Physical functioning and mental health in patients with chronic medical conditions.

There is evidence to suggest that a decline in physical functioning with advancing age is independent of mental health, which appears to remain relatively stable. There is additional evidence to suggest that those with a chronic disease also experience a decline in physical function while the mental health remains relatively stable. Using a cross-sectional design, data from the US population norms for the Medical Outcomes Study SF-36 are examined and compared to SF-36 data collected for four patient groups. Patient groups include kidney dialysis patients, multiple sclerosis patients, kidney transplant patients and patients with severe osteoarthritis of the hip prior to total hip replacement. Overall scores and scores within 10-year age groupings are examined in order to compare the physical functioning and mental health scores of the general population with those of the four patient groups. Results support the hypothesis that physical functioning declines with advancing age and with the development of chronic disease, but mental health remains remarkably stable regardless of chronic disease and/or advancing age. This observation suggests a process of psychological adjustment or adaptation to the physical difficulties encountered with advanced age or disability, and implies that this adjustment process may in fact be quite strong.

Determinants of 6-12 month postoperative functional status and pain after elective total hip replacement.

OBJECTIVE: The goal of this pilot project was to quantify outcomes of elective total hip replacement through risk adjustment modeling. DESIGN: A retrospective cohort study of patients who underwent elective total hip replacement (THR) during 1991 at the Orthopaedic and Arthritic Hospital in Toronto. STUDY PARTICIPANTS: All patients undergoing elective total hip replacement with a confirmed diagnosis of osteoarthritis were asked to participate in the study; 193 patients agreed. OUTCOME MEASURES: Participants were asked to complete the WOMAC Osteoarthritis Index and the RAND 36-item Health Survey 6 months to 1 year post-operatively. Pre-operative information on pain and functional status was obtained from the patients' medical record. RESULTS: The results indicate that 93% of patients studied reported at least one significant co-morbidity. The mean pre-operative pain score was 7.5 on a 0-10 scale and average change in pain was 4.8. Regression analyses indicate that increased body mass index is associated with lower post-operative functional status and increased post-operative pain. The amount of pain relief the patient was able to obtain pre-operatively using non-surgical interventions was associated with a better outcome.

Quantity of dialysis: quality of life--what is the relationship?

Health related quality of life (HRQOL) is increasingly being used to evaluate physical and psychosocial parameters in patients receiving dialysis. In patients with chronic illness, these indices are important adjuncts to biochemical measurements. Inadequate dialysis with low urea clearance (Kt/Vurea) has been linked to adverse outcomes in dialysis patients. Little is known about the relationship between dialysis adequacy and patient reported HRQOL. We evaluated HRQOL in 55 hemodialysis and 60 peritoneal dialysis patients using the RAND 36 Item Health Survey 1.0, measuring the following: physical functioning; role limitations (physical); role limitations (emotional); social functioning; emotional well being; pain; energy; and general health perceptions. Kt/V was also calculated for each patient. Mean HD Kt/V was 1.44 +/- 0.31 (range, 0.5-2.0); mean weekly PD Kt/V was 2.28 +/- 0.90 (range, 1.13-6.02). The relationship between Kt/V and HRQOL was tested using Pearson's correlation. No significant association was found for either treatment group between Kt/V and any of the domains of HRQOL. Thus, HRQOL seems to be influenced by factors other than dialysis adequacy, enhancing its role as an independent measure of patient problems otherwise undetected by traditional objective parameters.

Self-delivery of hemodialysis care: a therapy in itself.

Patient autonomy, sense of control, and well-being are thought to be enhanced by self-care hemodialysis as a therapy for end-stage renal disease. Dialysis in a satellite setting reduces travel time and can diminish therapy intrusiveness. Health-related quality of life (HRQOL), in terms of functional status and well-being, was measured in a group of patients trained for self-care, and then measured again after these patients were transferred to a satellite unit. Comparison was made with an age- and comorbidity-matched cohort of full-care patients. Patients trained for self-care tended to score higher than the full-care patients in the psychosocial domains of HRQOL, such as role function, social function, and emotional well-being, before and after transfer to the satellite unit. Physiological measurements did not differ significantly between groups at any time during the study, indicating that differences in HRQOL were not attributable to differences in metabolic stability. We conclude that patients trained for self-care hemodialysis experience better subjective quality of life than their full-care counterparts. This study highlights both the usefulness of measuring HRQOL as an outcome of hemodialysis therapy and the potential benefits of therapies such as self-care and satellite dialysis.

Measurement of health-related quality of life in multiple sclerosis patients.

BACKGROUND: Patient outcomes in multiple sclerosis (MS) have generally been measured by their neurological impairment using specific scales such as the Kurtzke Expanded Disability Status Scale (EDSS). However, this scale does not measure the multiple dimensions of health-related quality of life (HRQOL) such as functional status and general well-being, which are also important outcomes along with disease-specific measurements. METHODS: HRQOL was measured in a group of 97 MS patients using the RAND 36-item Health Survey 1.0. The EDSS score was assigned by the clinic neurologist. Additional data were collected from the clinical record for each patient. RESULTS: MS patients scored poorly in a number of HRQOL domains such as physical and role functioning and energy or vitality. Disability as quantified by the EDSS correlated only with the physical functioning domain. Regression models were developed to measure the relationship between patient characteristics (independent variables) and HRQOL domains (dependent variables). DISCUSSION: A number of patient characteristics were associated with higher or lower scores on the HRQOL domains. Of particular interest is the finding that a family history of MS was associated with poorer physical and social functioning as well as more pain and less vitality. The occurrence of seizures had a negative impact on role functioning, social functioning and general health perceptions. HRQOL gives caregivers a broader measure of disease burden than the EDSS alone, and should be useful in planning and monitoring interventions.