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Efficacy of a single oral dose of 200,000 IU of oil-soluble vitamin A in measles-associated morbidity.

The authors assessed the efficacy of the World Health Organization (WHO) recommendation of 200,000 IU of vitamin A in oil to treat acute non-xerophthalmic measles patients. Acute measles patients who did not require hospitalization were enrolled in a randomized, double-masked, clinical trial of vitamin A (n=90) versus placebo (n=110) carried out in Ndola, Zambia, in 1991. Measles-associated morbidity was defined by the presence of signs and symptoms of acute respiratory infection. Daily evaluations for the first 3 days were followed by weekly visits for a month at urban health centers. Baseline demographic, clinical, and biochemical characteristics were similar in both groups. Cross-sectional analysis of morbidity status, by group, at each weekly evaluation showed no significant differences until week 4, when more placebo-treated patients had cough or pneumonia (p=0.005). However, longitudinal analysis, which looked at changes among individuals and controlled for initial health status, showed more equivocal results. The odds ratio for the development of pneumonia in patients with measles cough in vitamin A-treated subjects was 0.73 (95% confidence interval (Cl) 0.30-1.80). The odds ratio for the development of measles-associated cough or pneumonia in asymptomatic measles patients was 0.52 (95% Cl 0.24-1.13), in favor of vitamin A, but the odds ratio for failing to improve from pneumonia in vitamin A-treated subjects was 1.23 (95% Cl 0.68-2.3), a result in favor of placebo. These results suggest that the evidence for the efficacy of one dose of vitamin A in oil to prevent measles complications is not as strong as that previously shown for two 200,000 IU doses of water-miscible vitamin A, and that the WHO recommendation may need to be reexamined.

Anthropometry↗

Longitudinal impact of mindfulness meditation on illness burden in solid-organ transplant recipients.

BACKGROUND: In 2001, more than 24000 solid-organ transplant surgeries were performed in the United States. Although survival rates have steadily risen over the past 2 decades, transplant recipients commonly experience a myriad of symptoms after transplantation that compromise quality of life. Anxiety, depression, and insomnia frequently occur despite excellent function of the transplanted organ. Use of complementary and alternative medicine has risen sharply over the past 10 years, particularly among people with chronic illnesses. METHODS: Twenty solid-organ transplant recipients were enrolled in a clinical trial of mindfulness-based stress reduction. During the 8-week course, subjects learned various forms of meditation and gentle hatha yoga. Participants were given audiotapes for home practice and maintained practice diaries. Longitudinal analysis focused on the impact of mindfulness-based stress reduction on symptom management, illness intrusion, and transplant-related stressors. RESULTS: Significant improvements in the quality and duration of sleep continued for 6 months after completion of the mindfulness-based stress reduction course. Improvements after the completion of the course were also noted in self-report measures of anxiety and depression. CONCLUSIONS: Mindfulness-based stress reduction is an effective treatment in improving the quality and duration of sleep. Because sleep is highly correlated with positive mental health and overall well-being, these findings suggest that mindfulness-based stress reduction has the potential of being an effective, accessible and low-cost intervention that could significantly change transplant recipients' overall health and well-being.

Adaptation, Psychological↗

Relative bias in diet history measurements: a quality control technique for dietary intervention trials.

OBJECTIVE: Investigation of relative bias in diet history measurement during dietary intervention trials. DESIGN: Retrospective analysis of human dietary data from two randomised controlled trials examining modified fat diets in the prevention and treatment of type II diabetes mellitus. SETTING: Wollongong, Australia. SUBJECTS: Thirty-five overweight, otherwise healthy subjects in trial 1 and 56 subjects with diabetes in trial 2. INTERVENTIONS: Diet history interviews and three-day weighed food records administered at one-month intervals in trial 1 and three-month intervals in trial 2. RESULTS: In a cross-sectional bias analysis, graphs of the association between bias and mean dietary intake showed that bias decreased in higher carbohydrate consumers in trial 1 (r = -0.344, P < 0.05). No other significant associations were found. In a longitudinal analysis, bias did not change over time in either trial. There were no significant differences in bias magnitudes between the trials, with the exception of monounsaturated fat measurement where bias was significantly greater and more positive in trial 2, indicating overestimation of monounsaturated fat intake with the diet history. Subjects in control and intervention groups underestimated energy, fat, saturated fat and alcohol intakes with the diet history in both trials. Overweight and obese individuals appeared to make the greatest contribution to the overall underestimation of saturated fat intake by the diet history regardless of whether they were in the control or intervention group and whether they were healthy or had diabetes. CONCLUSION: Bias in diet history measurement appears to be macronutrient-specific, with energy, fat and saturated fat consistently underreported in the interview by subjects with and without diabetes and in both intervention and control groups in a dietary intervention trial. Relative bias analysis appears to be an informative tool in quality control for dietary intervention trials when biochemical markers are unavailable.

Adult↗

Neuropsychological and cerebral metabolic function in early vs late onset dementia of the Alzheimer type.

Differences in age at onset of dementia of the Alzheimer type (DAT) have been associated with differences in cognitive impairments and course of the disease. To investigate this, we examined cerebral metabolism and cognitive performance in early and late onset DAT patients, who had equivalent duration and severity of illness. Regional cerebral metabolic rates for glucose were measured in the resting state by positron emission tomography using [18F]2-fluoro-2-deoxy-D-glucose. A cross-sectional analysis showed no significant differences between the two groups in performance on neuropsychological tests, but the early onset patients showed significantly more parietal metabolic dysfunction than did the late onset patients. Longitudinal analysis showed no significant differences between early and late onset patients in rate of cognitive decline over a mean interval of 19 months. Thus, our results do not support the hypothesis of different subgroups in DAT based on age at onset, nor suggest a faster rate of cognitive decline in younger patients.

Age Factors↗

Relationship between nutritional status and lung function in cystic fibrosis: cross sectional and longitudinal analyses from the German CF quality assurance (CFQA) project.

BACKGROUND: The German cystic fibrosis (CF) quality assurance (CFQA) project is a patient registry for CF which was founded in 1995. Relevant clinical and laboratory data, respiratory function test results, complications, and CF treatments are entered into the database once a year for each patient. Using the database, a study was undertaken to elucidate the relationship between nutrition and lung function in a large patient cohort by cross sectional and longitudinal analysis. METHODS: A cohort of 3298 patients above 2 years of age was analysed. Patients were grouped according to the presence or absence of malnutrition (wasting and/or stunting). Cross sectional and longitudinal analyses over 2 and 3 years including mixed model analyses were performed. RESULTS: The prevalence of abnormal weight for height (<90% predicted) increased with age from 19% in children aged <6 years to 38% in adults with CF. Patients with malnutrition had significantly lower mean values of vital capacity, arterial oxygen tension (PO(2)), and forced expiratory volume in 1 second (FEV(1)) and higher serum IgG (p<0.05). Pseudomonas aeruginosa infection was also associated with decreased pulmonary function. Malnourished adolescents aged 12-18 years experienced a serious decline in FEV(1) of about 20% predicted, whereas mean FEV(1) values remained stable at above 80% predicted in adolescents of normal weight. Longitudinal follow up showed that malnourished patients of all ages and those with P aeruginosa infection had significantly worse lung function than their normally nourished counterparts and a greater yearly loss of FEV(1) % predicted. During 1 year of observation adolescents who experienced a >5% predicted decrease in weight for height had a concomitant mean loss of FEV(1) of 16.5% predicted during that year, whereas patients who gained relative weight had a parallel increase in FEV(1) of 2.1% predicted. CONCLUSIONS: These data emphasise the close relationship between nutrition, lung function, and clinical course in CF. Normal body weight and absence of P aeruginosa infection was associated with better preservation of lung function.

Adolescent↗

Fifteen year follow-up study of VC and FEV1 in dust-exposed workers.

A baseline survey of 3457 male workers exposed to various forms of dust from 11 medical facilities throughout Japan was carried out in 1978 or 1979. We completed the present follow-up study 15 years later on 693 of the men. Vital capacity (VC) and forced expiratory volume in one second (FEV1) were analyzed as indices of lung function. We examined factors that affected both baseline and interval changes in VC and FEV1 by stepwise multiple regression analysis. In the cross-sectional data analysis of baseline, height, profusion rate (PR) and age were selected as predictor variables for VC and FEV1, additionally duration of working for FEV1. It indicated that baseline VC decreased by 84.0 ml with each increase in PR classification. Similarly, baseline FEV1 decreased by 146.6 ml with increasing PR. Baseline VC and FEV1 were both positively influenced by subject height. In the longitudinal analysis, baseline PR, age and smoking habits were selected for predictor variables for decline of VC and FEV1. It indicated a negative influence of baseline PR classification on VC and FEV1 changes (-5.0 and -7.5 ml/y, respectively). Smoking decreased VC and FEV1 by 6.1 and 5.8 ml/y, respectively.

Adult↗

Normal gross motor development: the influences of race, sex and socio-economic status.

The ages at attainment of 12 gross motor milestones were obtained prospectively during well-baby visits in the first two years of life for 381 children. All had been born at term and were judged to be normal at one year. A longitudinal analysis, using an index summarizing each child's progress for eight selected milestones, is reported for the 284 children for whom data were complete. A high percentage of parents were able to report the age at attaining milestones with an acceptable degree of variability. The children attained milestones at earlier ages than traditionally reported. There were only minor sex differences in age at attainment, but black children attained milestones earlier than white children.

Analysis of Variance↗

Red cell aplasia due to host type isohemagglutinins with exuberant red cell progenitor production of donor type in an ABO-mismatched allogeneic bone marrow transplant recipient.

ABO-mismatched bone marrow transplants have resulted in delayed red cell production in patients who have persistently elevated anti-ABO isohemagglutinin titers. We present a patient with chronic myelogenous leukemia who received an HLA-matched, ABO-incompatible bone marrow transplant from his sister. Post-transplant, he developed pure red cell aplasia with exuberant production of donor red cell precursors by in vitro BFU-E assay. Restriction fragment length polymorphism (RFLP) analysis of bone marrow, peripheral blood and BFU-E colonies demonstrated only donor type DNA post-transplant. However, the patient had persistently elevated isohemagglutinin titer and Ph1 chromosome-positive metaphases on chromosome analysis, indicating the presence of persistent host lymphocytes. With onset of acute graft vs. host disease (GVHD), the isohemagglutinin titer dropped, Ph1 chromosome-positive metaphases disappeared, and full hematopoietic recovery ensued. Longitudinal analysis of RFLP's, isohemagglutinin titers and chromosomes may be helpful in understanding the immunological interplay following allogeneic bone marrow transplantation.

ABO Blood-Group System↗

Growth hormone treatment of idiopathic short stature: analysis of the database from KIGS, the Kabi Pharmacia International Growth Study.

Within the Kabi Pharmacia International Growth Study (KIGS) database, there is information on 1017 (700 male/317 female) patients with idiopathic short stature (ISS). These patients were started on recombinant human growth hormone (GH) at a median age of 10.8 years, a bone age of -1.8 SDS, a height of -2.6 SDS and a predicted adult height (PAH) (Bailey-Pinneau method) of -2.5 SDS. The median dose of GH was 0.6 IU/kg body weight/week and the frequency of injections was six/week. According to the relationship with target height the patients were classified into 'familial short stature (FSS)' (height SDS > target height SDS -1.28) and into 'non-FSS' (height SDS < target height SDS -1.28). During the first year of GH treatment there was an overall increment in the median height velocity from 4.4 to 7.4 cm/year. Over 3 years of GH treatment, cross-sectional analysis demonstrated an overall increment in median PAH of 1.2 SDS. There was a positive correlation between gain in PAH and the GH dose (n = 202, r = 0.18, p < 0.01) during the first year. Longitudinal analysis in 84 patients showed an overall increment of PAH of 0.7 SDS over 2 years of treatment. When applying the KIGS first-year prediction model for patients with idiopathic GH deficiency on cohorts of prepubertal children with FSS and non-FSS, a lower responsiveness to GH in the non-FSS group was observed. It is concluded that higher than substitutive doses of GH are required for the long-term improvement of growth in ISS.

Adolescent↗

A new strategy for studying in vitro the drug susceptibility of clinical isolates of human hepatitis B virus.

Resistance of hepatitis B virus (HBV) to antivirals has become a major clinical problem. Our objective was to develop a new method for the cloning of naturally occurring HBV genomes and a phenotypic assay capable of assessing HBV drug susceptibility and DNA synthesis capacity in vitro. Viral DNA was extracted from sera and was amplified by polymerase chain reaction, and amplicons were cloned into vectors that enable, after cell transfection, the initiation of the intracellular HBV replication cycle. Single or multiple clones were used to transfect Huh7 cells. The viral DNA synthesis capacity and drug susceptibility were determined by measuring the level of intracellular DNA intermediate, synthesized in absence or presence of antiviral, using Southern blot analysis. We have developed, calibrated, then used this phenotypic assay to determine the drug susceptibility of HBV quasispecies isolated throughout the course of therapy from patients selected according to their mutation profile. A multiclonal and longitudinal analysis enabled us to measure the variation of drug susceptibility of different viral quasispecies by comparison of IC(50)/IC(90)s with standards. The presence of famciclovir- or lamivudine-induced mutations in the viral population caused a change in viral DNA synthesis capacity and drug susceptibility in vitro, demonstrating the clinical relevance of the assay. In conclusion, our phenotypic assay enables the in vitro characterization of DNA synthesis capacity and drug susceptibility of HBV quasispecies isolated from patients. This assay should allow a better monitoring of patients undergoing antiviral therapy, as well as the screening of novel drugs on emerging resistant strains.

Calibration↗

Monitoring of autoregulation using laser Doppler flowmetry in patients with head injury.

The authors studied 31 comatose head-injured patients to assess the clinical usefulness of laser Doppler flowmetry (LDF) in continuous autoregulation monitoring. The LDF probes were placed on the surface of the cerebral cortex. Data on LDF, intracranial pressure (ICP), and arterial blood pressure (ABP) were recorded and continuously entered into a computer. The data were broken down into multiple segments of 15 minutes' duration (epochs). Epochs showing rapid change in cerebral perfusion pressure (CPP), change in CPP of less than 10 mm Hg, LDF values of less than five arbitrary units, and loss of ABP/ICP waveform were excluded from further analysis. A linear relationship between LDF and CPP in individual epochs was used as an indicator of loss of autoregulation. The relationship between LDF and CPP changed with time, indicating improvement or deterioration in autoregulation. Longitudinal analysis of all the epochs measured in a patient revealed three patterns of progress: 1) intact autoregulation; 2) transient loss; and 3) persistent loss of autoregulation. All five patients with intact autoregulation had a good outcome. Ten patients experienced transient loss of autoregulation; of these four had a good outcome, five were moderately disabled and one was severely disabled. Transient impairment of autoregulation did not always indicate poor outcome, provided the impaired autoregulation responded to treatment. In 11 patients who had persistent loss of autoregulation, nine died and two were severely disabled. In five cases the LDF probe lost contact with the cerebral cortex and no useful information was obtained. Real-time measurement of autoregulation using LDF and CPP monitors was achieved and the findings were related to outcome in these patients.

Adult↗

Storage mites in the work environment of farmers.

Occurrence of storage mites was studied in cow houses and hay stores on 19 farms, most of which were located in eastern Finland. On two farms we did a monthly follow-up. Mites were extracted from hay by sieving, using the so-called "water trap" and for longitudinal analysis, with a warm extractor. The mites isolated in the water trap were identified under a microscope. Contrary to previous Finnish findings, there apparently were more mites in cow houses than in hay stores. In cow houses there were an average of 1,650 mites per gram of dust and in hay stores about 1,100 mites per gram of dust. Acarus siro was most abundant in cow houses (67% of all the mites found in cow houses) and more than 1,000 mites/g of sample material. The second most numerous was Tydeus spp. (178 mites/g of sample material). After that, Lepidoglyphus destructor, Tyrophagus longior, Glycyphagus domesticus occurred in about equal numbers. In hay stores Tydeus spp. was slightly more common (341 mites/g of sample material) than Acarus siro (317 mites/g of sample material). Lepidoglyphus destructor (64 mites/g of sample material), Glycyphagus domesticus (60 mites/g of sample material) and Mesostigmata (57 mites/g of dust) occurred in about equal numbers. According to the analysis based on one farm the number of mites in hay stores decreased considerably from September to February. Based on four measurements in the cow house of another farm, however, no steady trend of longitudinal variation could be found. Mites were most abundant at the beginning of January. There were few or no mites in bales of dry and unmoulded hay.

Agricultural Workers' Diseases↗

CD8 T-cell responses in early HIV-1 infection are skewed towards high entropy peptides.

OBJECTIVE: To understand the mechanisms underlying the differential targeting of T-cell responses during HIV-1 disease progression. DESIGN: We performed a cross-sectional analysis of HIV specific CD8 T-cell responses in peripheral blood mononuclear cells (PBMC) obtained from 21 subjects with well characterized acute or early infection and 88 subjects with chronic HIV-1 infection. We also performed a longitudinal analysis of T-cell responses in five early infected subjects one of whom was studied extensively over a 4-year-period. METHODS: PBMC were stimulated with pools of peptides encompassing all of the HIV-1 proteins in an interferon-gamma ELISpot assay. A mean entropy score was calculated for each peptide in the HIV-1 genome. RESULTS: The early infected group preferentially targeted variable peptides with higher entropy while responses towards more conserved peptides with lower entropy predominated in the group with chronic infection. In five early infected subjects followed longitudinally, responses to variable proteins declined while those to conserved proteins increased over time. In the subject who was followed for 4 years, epitopes in Vif and Nef were targeted early and escape occurred in three of these four epitopes. During the chronic phase of his infection, the early responses waned with an associated increase in breadth of T-cell responses mainly to Gag and Pol epitopes. CONCLUSION: Taken together, these data demonstrate that HIV-specific CD8 T cells are directed preferentially to the variable peptides in early infection but diminish in frequency during chronic disease, in large part due to cytotoxic T lymphocyte escape.

Acute Disease↗

A comparative study of three methods for analysing longitudinal pulmonary function data.

We compare three methods of longitudinal analysis of pulmonary function data. Our data set is taken from a study of exposure to toluene diisocyanate (TDI) vapours in a new manufacturing plant. The first two methods are a two-stage weighted regression method and maximum likelihood estimation via the EM algorithm, and these give very similar results. The third method, regression with an autoregressive error structure, was not successfully implemented, and in our view needs better documentation.

Adult↗

Longitudinal and cross-sectional estimates of pulmonary function decline in never-smoking adults.

This paper describes methods for simultaneous cross-sectional and longitudinal analysis of repeated measurements obtained in cohort studies with regular examination schedules, then uses these methods to describe age-related changes in pulmonary function level among nonsmoking participants in the Six Cities Study, a longitudinal study of air pollution and respiratory health conducted between 1974 and 1983 in Watertown, Massachusetts; Kingston and Harriman, Tennessee; St. Louis, Missouri; Steubenville, Ohio; Portage, Wisconsin; and Topeka, Kansas. The subjects, initially aged 25-74, were examined on three occasions at 3-year intervals. Individual rates of loss increased more rapidly with age than predicted from the cross-sectional model. For example, for a male of height 1.75 m, the cross-sectional model predicted an increase in the annual rate of loss of FEV1 from 23.7 ml/yr at age 25 to 39.0 ml/yr at age 75, while the longitudinal model gave rates of loss increasing from 12.9 ml/yr at age 25 to 58.2 ml/yr at age 75. These results contrast with those of other studies comparing longitudinal and cross-sectional estimates of pulmonary function loss.

Adult↗

Interrelationships among quantity of human cytomegalovirus (HCMV) DNA in blood, donor-recipient serostatus, and administration of methylprednisolone as risk factors for HCMV disease following liver transplantation.

Longitudinal analysis of 162 liver transplant recipients identified 51 patients who were viremic. Virus load was determined in 47 of these patients using quantitative-competitive polymerase chain reaction. Peak virus load was significantly higher in 20 symptomatic patients than 27 asymptomatic patients (P < .0001). Elevated virus load, donor seropositivity, and total methylprednisolone dosage were risk factors for human cytomegalovirus (HCMV) disease (odds ratio [OR], 2.22/0.25 log10 increase in virus load, P = .001; OR, 4.11, P = .05; OR, 1.30/1-g increment in methylprednisolone, P = .01). Methylprednisolone and virus load were independent risk factors in a multivariate analysis (OR, 2.70/1-g increase, P = .003; OR, 1.61/0.25 log10 increase, P = .03, respectively). Virus loads of 10(4.75)-10(5.25) genomes/mL of blood were associated with an increased disease probability; the latter was shifted to lower virus loads with increasing quantities of methylprednisolone. These data illustrate the central role of virus load in HCMV pathogenesis.

Adolescent↗

Who you live with and where you live: setting the context for health using multiple membership multilevel models.

STUDY OBJECTIVE: Previous studies into the effect of area of residence on individuals' health have not accounted for changing residency over time, although few people remain resident in the same area throughout their life. Furthermore, few studies of area effects on health have accounted for the clustering of health at the household level. These methodological problems may have led previous studies to under estimate or over estimate the size of area level effects. This study uses multiple membership multilevel models to investigate whether longitudinal analyses of area effects on health need to take account of clustering at the household level. SETTING AND PARTICIPANTS: A longitudinal survey (1991-1999) of a nationally representative sample of British households (5511 households with 10 264 adult members). DESIGN: Two level (individuals within households or areas) and three level (individuals within households within areas) multiple membership models of SF-36 physical and mental health functioning scores at wave nine were analysed adjusting for age, gender, education, marital, employment, and smoking status from previous waves. RESULTS: Physical and mental health functioning seem to cluster within households. Accounting for changes in household membership over time increases estimates of the clustering in functioning at the household level. The clustering of functioning within area wards is reduced when the clustering within households and risk factors for functioning are taken into account. CONCLUSIONS: Clustered sampling units within study designs should be taken account of in individual level analyses. Changes in these units over time should be accounted for in longitudinal analysis.

Adolescent↗

Caries experience and mutans streptococci as indicators of caries incidence.

Studies indicate that previous caries experience can influence future caries development; however, caries-free individuals also may develop caries. The aim of this study was to examine the relationship between baseline caries experience and salivary mutans streptococci (SMS) levels as an indicator for predicting caries incidence in pre-school children. One hundred forty-eight preschool children (mean baseline age, 3-8 years) of low socioeconomic status were examined for dental caries and SMS levels at baseline and annually for 2 years. All children were identified at baseline as either caries free or caries positive. The 2-year delta dmfs scores for both groups were evaluated as 0, 1-2, 3-4, or > 4. The children's baseline SMS levels were categorized as low (0 CFU), moderate (1-50 CFU), or high (> 50 CFU), and were recoded to assigned ranges of 1, 2, and 3, respectively, in each year for longitudinal analysis. Both the caries-free and caries-positive groups had high SMS levels associated with the greatest delta dmfs, and when SMS ranges were added for the three examination years (minimum = 3, maximum = 9), the mean second-year dmfs scores varied directly as the sum of the ranges. Results from this study suggest that SMS levels may be useful in identifying and predicting future caries in preschool children, independent of baseline caries experience.

Analysis of Variance↗