The effect of human leukocyte antigen A1 and B35-Cw4 on sustained BK polyomavirus DNAemia after renal transplantation.

Human leukocyte antigen (HLA) class I presentation pathway plays a central role in natural killer (NK) cell and cytotoxic T-cell activities against BK polyomavirus (BKPyV) DNAemia. We determined the risk of sustained BKPyV DNAemia in 175 consecutive renal transplant recipients considering the simultaneous effect of donor/recipient HLA class I antigens and pre- or post-transplant variables. Median (IQR) age was 53 (44-64) years, and 37% of patients were female. 40 patients (22.9%) developed sustained BKPyV DNAemia [median (IQR) viral load: 9740 (4350-17 125) copies/ml]. In the Cox proportional hazard analysis, HLA-A1 (HR: 3.06, 95% CI: 1.51-6.17) and HLA-B35-Cw4 (HR: 4.63, 95% CI: 2.12-10.14) significantly increased the risk of sustained BKPyV DNAemia, while 2 HLA-C mismatches provided a marginally protective effect (HR: 0.32, 95% CI: 0.10-0.98). HLA-Cw4 is a ligand for NK cell inhibitory receptor, and HLA-B35 is in strong linkage disequilibrium with the HLA-Cw4 allele. The association between HLA-B35-Cw4 expression and sustained BKPyV DNAemia supports the important role of cytotoxic T cells and NK cells that would normally control BKPyV activation through engagement with immunoglobulin-like killer receptors (KIRs). Further studies are required to investigate the effect of HLA-C alleles along with NK cell activity against BKPyV DNAemia.

Assessing the relationship between water and nutrition knowledge and beverage consumption habits in children.

OBJECTIVE: To examine the relationship between knowledge and beverage consumption habits among children. DESIGN: Cross-sectional analysis. Linear regression was used to identify sociodemographic, dietary and behavioural determinants of beverage consumption and knowledge, and to describe the relationships between children's knowledge and water and sugar-sweetened beverage (SSB) consumption. SETTINGS: Seventeen elementary schools in London, Ontario, Canada. PARTICIPANTS: A total of 1049 children aged 8-14 years. RESULTS: Knowledge scores were low overall. Children with higher knowledge scores consumed significantly fewer SSB (ß = -0·33; 95 % CI -0·49, -0·18; P < 0·0001) and significantly more water (ß = 0·34; 95 % CI 0·16, 0·52; P = 0·0002). More frequent refillable water bottle use, lower junk food consumption, lower fruit and vegetable consumption, female sex, higher parental education, two-parent households and not participating in a milk programme were associated with a higher water consumption. Male sex, higher junk food consumption, single-parent households, lower parental education, participating in a milk programme, less frequent refillable water bottle use and permission to leave school grounds at lunchtime were associated with a higher SSB consumption. Water was the most frequently consumed beverage; however, 79 % of respondents reported consuming an SSB at least once daily and 50 % reported consuming an SSB three or more times daily. CONCLUSIONS: Elementary-school children have relatively low nutrition and water knowledge and consume high proportions of SSB. Higher knowledge is associated with increased water consumption and reduced SSB consumption. Interventions to increase knowledge may be effective at improving children's beverage consumption habits.

Involvement of Informal Caregivers in Preventing Falls in Older Adults with Cognitive Impairment: A Rapid Review.

BACKGROUND: The prevalence of falls and related injuries is double in older adults with cognitive impairment compared with cognitively healthy older adults. A growing body of literature shows that falls prevention interventions in the cognitively impaired are difficult to implement and that the feasibility and adherence to interventions depend on a number of factors including informal caregiver involvement. However, no systematic review exists on the topic. OBJECTIVE: Our objective is to determine whether involvement of informal caregivers can reduce falls in older adults with cognitive impairment. METHODS: Rapid review following Cochrane collaboration guidelines. RESULTS: Seven randomized controlled trials were identified involving 2,202 participants. We identified the following areas where informal caregiving may have an important role in fall prevention in older adults with cognitive impairment: 1) enhancing adherence to the exercise program; 2) identifying and recording falls incidents and circumstances; 3) identifying and modifying possible environmental falls risk factors inside patient's home; and 4) playing an active role in modifying lifestyle in terms of diet/nutrition, limiting antipsychotics, and avoiding movements risking falls. However, informal caregiver involvement was identified as an incidental finding in these studies and the level of evidence ranged from low to moderate. CONCLUSION: Informal caregiver involvement in planning and delivering interventions to reduce falls has been found to increase the adherence of individuals with cognitive impairment in falls prevention programs. Future research should address whether involvement of informal caregivers may improve efficacy of prevention programs by reducing the number of falls as a primary outcome.

Impact of PubMed search filters on the retrieval of evidence by physicians.

BACKGROUND: Physicians face challenges when searching PubMed for research evidence, and they may miss relevant articles while retrieving too many nonrelevant articles. We investigated whether the use of search filters in PubMed improves searching by physicians. METHODS: We asked a random sample of Canadian nephrologists to answer unique clinical questions derived from 100 systematic reviews of renal therapy. Physicians provided the search terms that they would type into PubMed to locate articles to answer these questions. We entered the physician-provided search terms into PubMed and applied two types of search filters alone or in combination: a methods-based filter designed to identify high-quality studies about treatment (clinical queries "therapy") and a topic-based filter designed to identify studies with renal content. We evaluated the comprehensiveness (proportion of relevant articles found) and efficiency (ratio of relevant to nonrelevant articles) of the filtered and nonfiltered searches. Primary studies included in the systematic reviews served as the reference standard for relevant articles. RESULTS: The average physician-provided search terms retrieved 46% of the relevant articles, while 6% of the retrieved articles were relevant (corrected) (the ratio of relevant to nonrelevant articles was 1:16). The use of both filters together produced a marked improvement in efficiency, resulting in a ratio of relevant to nonrelevant articles of 1:5 (16 percentage point improvement; 99% confidence interval 9% to 22%; p < 0.003) with no substantive change in comprehensiveness (44% of relevant articles found; p = 0.55). INTERPRETATION: The use of PubMed search filters improves the efficiency of physician searches. Improved search performance may enhance the transfer of research into practice and improve patient care.

Accuracy of family history of hemochromatosis or iron overload: the hemochromatosis and iron overload screening study.

BACKGROUND & AIMS: The aim of this study was to assess the analytic validity of self-reported family history of hemochromatosis or iron overload. METHODS: A total of 141 probands, 549 family members, and 641 controls participated in the primary care Hemochromatosis and Iron Overload Screening Study. Participants received a postscreening clinical examination and completed questionnaires about personal and family histories of hemochromatosis or iron overload, arthritis, diabetes, liver disease, and heart disease. We evaluated sensitivities and specificities of proband-reported family history, and concordance of HFE genotype C282Y/C282Y in probands and siblings who reported having hemochromatosis or iron overload. RESULTS: The sensitivities of proband-reported family history ranged from 81.4% for hemochromatosis or iron overload to 18.4% for liver disease; specificities for diabetes, liver disease, and heart disease were greater than 94%. Hemochromatosis or iron overload was associated with a positive family history across all racial/ethnic groups in the study (odds ratio, 14.53; 95% confidence intervals, 7.41-28.49; P < .0001) and among Caucasians (odds ratio, 16.98; 95% confidence intervals, 7.53-38.32; P < .0001). There was 100% concordance of HFE genotype C282Y/C282Y in 6 probands and 8 of their siblings who reported having hemochromatosis or iron overload. CONCLUSIONS: Self-reported family history of hemochromatosis or iron overload can be used to identify individuals whose risk of hemochromatosis or iron overload and associated conditions is increased. These individuals could benefit from further evaluation with iron phenotyping and HFE mutation analysis.

Clinical manifestations of hemochromatosis in HFE C282Y homozygotes identified by screening.

BACKGROUND: Patients with hemochromatosis may suffer organ damage from iron overload, often with serious clinical consequences. OBJECTIVE: To assess prevalences of self-reported symptoms and clinical signs and conditions in persons homozygous for the hemochromatosis gene (HFE) mutation (C282Y) identified by screening. METHODS: Participants were adults 25 years of age or older enrolled in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. C282Y homozygotes (n=282) were compared with control participants without the HFE C282Y or H63D alleles (ie, wild type/wild type; n=364). RESULTS: Previously diagnosed C282Y homozygotes and newly diagnosed homozygotes with elevated serum ferritin levels had higher prevalences of certain symptoms such as chronic fatigue (OR 2.8; 95% CI 1.34 to 5.95, and OR 2.0; 95% CI 1.07 to 3.75, respectively), and had more hyperpigmentation on physical examination (OR 4.7; 95% CI 1.50 to 15.06, and OR 3.7; 95% CI 1.10 to 12.16, respectively) and swelling or tenderness of the second and third metacarpophalangeal joints (OR 4.2; 95% CI 1.37 to 13.03, and OR 3.3; 95% CI 1.17 to 9.49, respectively) than control subjects. Joint stiffness was also more common among newly diagnosed C282Y homozygotes with elevated serum ferritin than among control subjects (OR 2.7; 95% CI 1.38 to 5.30). However, the sex- and age-adjusted prevalences of self-reported symptoms and signs of liver disease, heart disease, diabetes and most other major clinical manifestations of hemochromatosis were similar in C282Y homozygotes and control subjects. CONCLUSIONS: Some symptoms and conditions associated with hemochromatosis were more prevalent among C282Y homozygotes identified by screening than among control subjects, but prevalences of most outcomes were similar in C282Y homozygotes and controls in this primary care-based study.

HFE C282Y homozygotes aged 25-29 years at HEIRS Study initial screening.

We characterized HFE C282Y homozygotes aged 25-29 years in the HEmochromatosis and IRon Overload Screening (HEIRS) Study using health questionnaire responses, transferrin saturation (TfSat), serum ferritin (SF), and HFE genotyping. In eight homozygotes, we used denaturing high-performance liquid chromatography and sequencing to search for HFE2 (= HJV), TFR2, HAMP, SLC40A1 (= FPN1), and FTL mutations. Sixteen of 4,008 White or Hispanic participants aged 25-29 years had C282Y homozygosity (15 White, 1 Hispanic); 15 were previously undiagnosed. Eleven had elevated TfSat; nine had elevated SF. None reported iron overload-associated abnormalities. No deleterious non-HFE mutations were detected. The prevalence of C282Y homozygosity in White or Hispanic HEIRS Study participants aged 25-29 years did not differ significantly from the prevalence of C282Y homozygosity in older White or Hispanic HEIRS Study participants. The prevalences of reports of iron overload-associated abnormalities were not significantly different in these 16 C282Y homozygotes and in HFE wt/wt control participants aged 25-29 years who did not report having hemochromatosis or iron overload. We conclude that C282Y homozygotes aged 25-29 years diagnosed by screening infrequently report having iron overload-associated abnormalities, although some have elevated SF. Screening using an elevated TfSat criterion would fail to detect some C282Y homozygotes aged 25-29 years.

Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study.

OBJECTIVE: We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study. RESEARCH DESIGN AND METHODS: Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis. RESULTS: The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center. CONCLUSIONS: Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload.

Regional cerebral cortical thickness correlates with autonomic outflow.

Dysregulation of autonomic control often develops with advancing age, favoring a chronic state of heightened sympathetic outflow with parasympathetic withdrawal. However, the mechanisms of this age-related autonomic impairment are not known. This study tested the hypothesis that inter-individual differences in autonomic outflow across the adult age-span are related to cerebral cortex thickness. A total of 55 healthy, active individuals participated in this study (21-73years; 18 female). Physical fitness was treated as a possible covariate (VO2peak: 26-81mL/kg/min). Cardiovagal baroreflex sensitivity, heart rate variability, and muscle sympathetic nerve activity (MSNA) were assessed during a laboratory session. T1-weighted images acquired at 3T facilitated measures of cortical thickness (Brain Voyager 2.8.4). A priori cortical regions of interest included the medial prefrontal cortex (MPFC) and insula cortex. Cortical thickness at the MPFC correlated strongly with markers of autonomic outflow including heart rate variability (ln-high frequency power (slope: -16, r2=0.65), SDNN (slope: 22, r2=0.22), total power (slope: 2872, r2=0.24)), and MSNA variables (burst frequency (slope: 1, r2=0.16), burst incidence (slope: -26, r2=0.62) and total MSNA (slope: -847, r2=0.56)). Further associations with burst incidence were observed within the left insula (p<0.05). Importantly, the strength of the relationship between autonomic variables and cortical thickness was determined by age, and was not altered following adjustments for cardiorespiratory fitness. The current results implicate cortical atrophy in the frontal lobe as a contributor to both the sympathetic and parasympathetic changes that occur with age.

Estimates of quality and reliability with the physiotherapy evidence-based database scale to assess the methodology of randomized controlled trials of pharmacological and nonpharmacological interventions.

BACKGROUND AND PURPOSE: Systematic reviews and meta-analyses often include an evaluation of the methodological quality of the individual studies that have been included, and are usually conducted by at least 2 individuals. The objective of this study was to assess the methodological quality and reliability of a series of randomized controlled trials (RCTs) of both pharmacological and nonpharmacological interventions by use of the 10-item Physiotherapy Evidence-Based Database (PEDro) Scale. METHODS: Two abstractors independently reviewed 81 RCTs assessing a variety of interventions. The Cohen kappa statistic and the intraclass correlation coefficient (ICC) were used to assess agreement between abstractors. RESULTS: The average total PEDro scores were 5.94 (SD=1.43) for all studies combined, 6.88 (SD=1.2) for pharmacological studies, and 5.29 (SD=1.26) for nonpharmacological studies. The median score for pharmacological studies was significantly higher than that for nonpharmacological studies (7 versus 5). Pair-wise kappa scores ranged from a low of .452 for concealed allocation among drug trials to perfect agreement (1.00) for randomization and reporting of results from between-group comparisons. The ICCs associated with the cumulative PEDro score were .91 (95% confidence interval [CI]=.83-.94) for all studies, .89 (95% CI=.78-.95) for pharmacological studies, and .91 (95% CI=.84-.952) for nonpharmacological studies. DISCUSSION AND CONCLUSION: The methodological quality for pharmacological interventions was significantly higher than that for nonpharmacological interventions. There was good agreement between raters at an individual item level and in total PEDro scores. A lack of reporting clarity, poor organization of the report, or the failure to include salient details contributed to less-than-perfect agreement between raters.

Geographic and racial/ethnic differences in HFE mutation frequencies in the Hemochromatosis and Iron Overload Screening (HEIRS) Study.

OBJECTIVE: To assess geographic differences in the frequencies of HFE C282Y and H63D genotypes in six racial/ethnic groups recruited in the Hemochromatosis and Iron Overload Screening (HEIRS) Study. DESIGN: HFE C282Y and H63D genotypes of 97,551 participants, ages > or = 25 years, who reported that they belonged to one of six racial/ethnic groups, were analyzed. HFE genotype frequencies were compared among the racial/ethnic groups and among the HEIRS Study field centers within each racial/ethnic group. RESULTS: The distribution of HFE C282Y and H63D genotypes differed among racial/ethnic groups (P<.0001) and among field centers in Hispanics, Asians, Whites, and Blacks (each P<.05). Genotype frequencies were similar among field centers in Native Americans and Pacific Islanders. Frequencies of C282Y and H63D genotypes were greatest in Whites. The lowest frequencies of C282Y genotypes were observed in Asians; Blacks had the lowest H63D genotype frequencies and the highest frequency of the wild-type genotype. Among racial/ethnic groups, Hispanics had the greatest variation in HFE genotypes across geographic regions. CONCLUSION: HFE C282Y and H63D genotype frequencies vary significantly between racial/ethnic groups and within some racial/ethnic groups across geographic regions.

The PEDro scale provides a more comprehensive measure of methodological quality than the Jadad scale in stroke rehabilitation literature.

OBJECTIVE: To systematically compare the PEDro scale and the Jadad scale when applied to the stroke rehabilitation literature. STUDY DESIGN AND SETTING: A literature search of multiple databases was used to identify all trials from 1968 through 2002. Each article was reviewed and assigned quality scores according to PEDro and Jadad criteria. Quality scores for both scales were compared using descriptive statistics. The correlation between the scales was estimated using the Pearson product moment correlation coefficient. RESULTS: 272 randomized controlled trials were retrieved and subjected to quality scoring to both the PEDro scale and the Jadad scale. Mean scores (with standard deviation) for the PEDro and Jadad scales were 5.78 (1.4) and 2.46 (1.1), respectively. The Pearson coefficient determined the PEDro and Jadad scales to be significantly correlated (r = .59, P < .01). Although significant, the correlation was not deemed to be very strong. When applied to physical or rehabilitation therapy studies only, the scales were slightly less correlated (r = .49, P < .01) than among drug-based studies (r = .52, P < .01). CONCLUSION: In the stroke rehabilitation literature, where double-blinding studies are often not possible due to the nature of the interventions, breaking down the levels of blinding and accounting for concealed allocation, intention-to-treat, and attrition is important. Accordingly, the PEDro scale provides a more comprehensive measure of methodological quality of the stroke literature.

Initial screening transferrin saturation values, serum ferritin concentrations, and HFE genotypes in whites and blacks in the Hemochromatosis and Iron Overload Screening Study.

We compared initial screening data of 44,082 white and 27,124 black Hemochromatosis and Iron Overload Screening (HEIRS) Study participants. Each underwent serum transferrin saturation (TfSat) and ferritin (SF) measurements without regard to fasting, and HFE C282Y and H63D genotyping. Elevated measurements were defined as: TfSat more than 50% (men), more than 45% (women); and SF more than 300 ng/ml (men), more than 200 ng/ml (women). Mean TfSat and percentages of participants with elevated TfSat were significantly greater in whites than in blacks. Mean SF and percentages of participants with elevated SF were significantly greater in blacks than in whites. TfSat and SF varied by gender and age in whites and blacks. Prevalences of genotypes that included either C282Y or H63D were significantly greater in whites than in blacks. The prevalence of elevated TfSat and SF plus genotypes C282Y/C282Y, C282Y/H63D, or H63D/H63D was 0.006 in whites and 0.0003 in blacks. Among whites with HFE C282Y homozygosity, 76.8% of men and 46.9% of women had elevated TfSat and SF values. Three black participants had HFE C282Y homozygosity; one had elevated TfSat and SF values. Possible explanations for differences in TfSat and SF in whites and blacks and pertinence to the detection of hemochromatosis, iron overload, and other disorders with similar phenotypes are discussed.

Natural history of C282Y homozygotes for hemochromatosis.

PURPOSE: To study the clinical outcomes of subjects who are homozygous for the C282Y mutation of the hemochromatosis gene. SUBJECTS AND METHODS: All patients referred to a tertiary referral centre for hemochromatosis were included. The study also included 16 C282Y homozygotes detected in a population screening study. RESULTS: The study comprised 277 C282Y homozygotes, including 16 nonexpressing C282Y homozygotes. The mean follow-up period was 7.3 years (range zero to 44 years). The actuarial survival rates of C282Y homozygotes at five, 10 and 20 years were 95%, 93% and 66%, respectively. Life-threatening diseases (cirrhosis, hepatocellular carcinoma, diabetes, heart disease) were present in 36% of male C282Y homozygotes and 19% of female C282Y homozygotes. Cirrhosis of the liver and diabetes were the major clinical symptoms affecting long term survival. Only one nonexpressing homozygote required venesection therapy during the follow-up period. CONCLUSIONS: Long term survival is excellent in C282Y homozygotes diagnosed and treated before the development of cirrhosis and diabetes.

The efficacy of stroke rehabilitation: a qualitative review.

A systematic review of randomized controlled trials published from 1970-2002 was conducted to assess whether specialized inpatient stroke rehabilitation is associated with improved outcomes compared to conventional care. Twelve studies involving 2,813 patients were included for detailed review. The methodological quality of the studies was assessed using the PEDro Scale. The outcomes of death, functional outcome, length of hospital stay, and rates of institutionalization were compared between the intervention and control group(s). Improved functional outcomes and reduced length of hospital stays were reported among patients receiving specialized rehabilitation in the majority of studies (7/12 and 5/8, respectively), while no differences in mortality or institutionalization were reported between the groups.

Early supported discharge in stroke rehabilitation.

A systematic review of the randomized controlled trials published from 1970-2002 was conducted to assess the effectiveness of early supported discharge programs in the context of stroke rehabilitation. Ten studies, including 1,286 patients, were selected for detailed review. The methodological quality of the studies was assessed using the PEDro Scale. The outcome assessed included functional outcomes, cost analysis, and length of hospital stay. Although the majority of studies reported no statistically significant differences in functional outcomes between the two groups, there was a reduction in hospital stays for patients receiving home-based therapy. These results suggest that patients with milder strokes who receive home-based therapies have similar functional outcomes to patients who receive traditional inpatient rehabilitation.

Gait retraining post stroke.

A major component of stroke rehabilitation focuses on gait restoration. The purpose of this review is to examine the efficacy of a variety of gait retraining techniques currently in clinical use, including strength training, functional electrical stimulation, treadmill training, partial body-weight support, EMG biofeedback, and splinting of the lower extremity. Forty-eight studies evaluating six gait enhancement techniques were reviewed. There is either strong or moderate evidence to support the use of strength training, EMG/biofeedback, and functional electrical stimulation as an adjunctive therapy in gait training, and there is either limited or conflicting evidence to support the use of ankle-foot orthosis, treadmill training, and partial body-weight support.

Rehabilitation of aphasia: more is better.

Although the most effective means of treating aphasia post stroke has not been determined, several areas of aphasia therapy have proven to be more effective than others. A recent study had determined that intense aphasia therapy over a short period of time has greater impact on recovery than less intense therapy over a longer period of time. Building upon the idea that more is better, this article examines other spects of aphasia therapy that may be combined to facilitate recovery.

Community reintegration after stroke.

A systematic review of the literature from 1970-2002 was conducted to highlight the issues facing stroke survivors and their families upon integration into the community. Areas of interests were social support, caregiver burden and depression, family interactions, family education intervention, social and leisure activities post stroke, and leisure therapy. Four studies were selected for detailed reviews of the effectiveness of social support, 10 studies for family education intervention, and 3 studies for leisure therapy post stroke. There was evidence that improved social support as an intervention improves outcomes and that an active educational-counseling approach has a positive impact on family functioning post stroke. However, consensus regarding leisure therapy was not achieved. This article also stresses the impact of caring for a stroke survivor and the effect it has on family functioning and caregiver burden.

Stroke Rehabilitation Evidence-Based Review: methodology.

The Stroke Rehabilitation Evidence-Based Review was intended to be an up-to-date review of all therapies associated with stroke rehabilitation including both therapeutic interventions and medications. This section describes the literature search strategy, the data abstraction process, and the scale used to evaluate the methodological quality of randomized controlled trials included in the review and the system upon which the levels of evidence were based.