Reproducibility and accuracy of a food frequency questionnaire used for diet intervention studies

The purpose of the present investigation was to determine whether altering the format of a food frequency questionnaire affected its accuracy and reproducibility. Three questionnaires were tested at one-month intervals. Questionnaire I contained 39 food items listed according to food categories. Questionnaire II contained 55 food items, presented according to the meal in which they were consumed. Questionnaire III contained 31 food items presented in a similar order to that in Questionnaire II. To determine the accuracy of the food frequency questionnaire, results were compared to those obtained from a simultaneously administered seven-day diet diary. Results from this study showed that food frequency questionnaires containing broad categories of food items presented in order of the meals in which they are consumed are the most reproducible. Highly reproducible results also can be obtained from seven-day diet diary, if data are calculated in terms of nutrients (i.e. carbohydrates, fats, proteins, etc.) and not specific food items. Finally, this study suggests that individuals more closely maintain their intake of nutrients, rather than specific food items.     

The effects of maternal drug dependence on neonatal mortality

Addiction in pregnancy has become an important health problem owing to the tendency of drug-dependent women to neglect general health care and to avoid seeking prenatal care. In addition, continued heroin administration during pregnancy carries additional risks for the maternal-fetal unit. Thus, there is an increased incidence of obstetrical and medical complications in these mothers, resulting in high incidences of prematurity, low birth weight and mortality in their infants. Therefore, there is a high neonatal mortality rate due to clinical conditions most commonly seen among premature infants. Data from three groups of drug-dependent women and their infants and one control group demonstrate that the high mortality rate, as well as the incidence of low birth weight, can be reduced to a rate similar to the control group in infants of mothers who receive comprehensive services that include prenatal care in conjunction with methadone maintenance.     

Acute neonatal effects of cocaine exposure during pregnancy

OBJECTIVE: To identify associations between cocaine exposure during pregnancy and medical conditions in newborn infants from birth through hospital discharge. DESIGN: Multisite, prospective, randomized study. SETTING: Brown University, University of Miami, University of Tennessee (Memphis), and Wayne State University.Subjects A total of 717 cocaine-exposed infants and 7442 nonexposed infants. MAIN OUTCOME MEASURES: Results of physical examination and conditions observed during hospitalization. RESULTS: Cocaine-exposed infants were about 1.2 weeks younger, weighed 536 g less, measured 2.6 cm shorter, and had head circumference 1.5 cm smaller than nonexposed infants (all P<.001). Results did not confirm previously reported abnormalities. Central and autonomic nervous system symptoms were more frequent in the exposed group: jittery/tremors (adjusted odds ratio, 2.17; 99% confidence interval, 1.44-3.29), high-pitched cry (2.44; 1.06-5.66), irritability (1.81; 1.18-2.80), excessive suck (3.58; 1.63-7.88), hyperalertness (7.78; 1.72-35.06), and autonomic instability (2.64; 1.17-5.95). No differences were detected in organ systems by ultrasound examination. Exposed infants had more infections (3.09; 1.76-5.45), including hepatitis (13.46; 7.46-24.29), syphilis (8.84; 3.74-20.88), and human immunodeficiency virus exposure (12.37; 2.20-69.51); were less often breastfed (0.26; 0.15-0.44); had more child protective services referrals (48.92; 28.77-83.20); and were more often not living with their biological mother (18.70; 10.53-33.20). CONCLUSIONS: Central and autonomic nervous system symptoms were more frequent in the exposed cohort and persisted in an adjusted analysis. They were usually transient and may be a true cocaine effect. Abnormal anatomic outcomes previously reported were not confirmed. Increased infections, particularly sexually transmitted diseases, pose a serious public health challenge. Exposure increased involvement of child protective services and out-of-home placement.     

The INFIR Cohort Study: investigating prediction, detection and pathogenesis of neuropathy and reactions in leprosy. Methods and baseline results of a cohort of multibacillary leprosy patients in north India

The aim of this study was to find predictors of neuropathy and reactions, determine the most sensitive methods for detecting peripheral neuropathy, study the pathogenesis of neuropathy and reactions and create a bank of specimen, backed up by detailed clinical documentation. A multi-centre cohort study of 303 multibacillary leprosy patients in Northern India was followed for 2 years. All newly registered MB patients requiring a full course of MDT, who were smear positive and/or had six or more skin lesions and/or had two or more nerve trunks involved, were eligible. A detailed history was taken and physical and neurological examinations were performed. Nerve function was assessed at each visit with nerve conduction testing, warm and cold detection thresholds, vibrometry, dynamometry, monofilaments and voluntary muscle testing. Because the latter two are widely used in leprosy clinics, they were used as 'gold standard' for sensory and motor impairment. Other outcome events were type 1 and 2 reactions and neuritis. All subjects had a skin biopsy at registration, repeated at the time of an outcome event, along with a nerve biopsy. These were examined using a variety of immunohistological techniques. Blood sampling for serological testing was done at every 4-weekly clinic visit. At diagnosis, 115 patients had an outcome event of recent onset. Many people had skin lesions overlying a major nerve trunk, which were shown to be significantly associated with an increased of sensory or motor impairment. The most important adjusted odds ratios for motor impairment were, facial 4.5 (1.3-16) and ulnar 3.5 (1.0-8.5); for sensory impairment they were, ulnar 2.9 (1.3-6.5), median 3.6 (1.1-12) and posterior tibial 4.0 (1.8-8.7). Nerve enlargement was found in 94% of patients, while only 24% and 3% had paraesthesia and nerve tenderness on palpation, respectively. These increased the risk of reactions only marginally. Seven subjects had abnormal tendon reflexes and seven abnormal joint position sense. In all but one case, these impairments were accompanied by abnormalities in two or more other nerve function tests and thus seemed to indicate more severe neuropathy. At diagnosis, 38% of a cohort of newly diagnosed MB leprosy patients had recent or new reactions or nerve damage at the time of intake into the study. The main risk factor for neuropathy found in this baseline analysis was the presence of skin lesions overlying nerve trunks. They increased the risk of sensory or motor impairment in the concerned nerve by 3-4 times. For some nerves, reactional signs in the lesions further increased this risk to 6-8 times the risk of those without such lesions. Patients with skin lesions overlying peripheral nerve trunks should be carefully monitored for development of sensory or motor impairment.     

Factors influencing survival in children with recurrent neuroblastoma

Despite advances in multimodal therapy for neuroblastoma, survival from advanced disease remains poor. Children are now offered a wide variety of salvage regimens following relapse. A retrospective review was performed on 31 patients with recurrent neuroblastoma treated at one institution between 1995 and 2001. At initial diagnosis, 27 patients had metastatic disease and 11 had N-myc amplification (NMA). The median time to recurrence from diagnosis was 16.1 months. Seventeen patients received salvage therapy, with a median of three salvage regimens per patient. The median survival time from relapse was 8.4 months. The median survival time was significantly shorter for recurrence less than 6 months after stem cell transplantation (2.9 vs. 13.3 months; P = 0.003) and for patients with NMA (2.7 vs. 15.1 months; P < 0.0001). Overall, salvage therapy led to a significantly longer median survival time (22.4 vs. 3.3 months; P = 0.0003); however, salvage therapy extended the median survival time only from 2.2 to 3.2 months for patients with NMA and from 0.7 to 5.8 months for patients with early relapse after stem cell transplantation. Multiple salvage regimens prolong survival significantly, especially for patients with no NMA and for relapses more than 6 months after stem cell transplantation, but the long-term disease-free survival after recurrent disease remains dismal.     

Novel mechanisms of tubulointerstitial injury in IgA nephropathy: a new therapeutic paradigm in the prevention of progressive renal failure

IgA nephropathy (IgAN) runs a highly variable clinical course with frequent involvement of tubulointerstitial damage. Notably, renal progression correlates more closely with the severity of tubulointerstitial lesions than with the degree of glomerular lesions In IgAN. Mesangial IgA deposition induces local release of cytokines, complement, and angiotensin II leading to glomerular inflammation. It remains unclear how mesangial IgA deposition leads to tubulointerstitial injury in IgAN. Moreover, IgA deposits are rarely detected in renal interstitium in IgAN. We hypothesize that mediators released from mesangial cells triggered by IgA deposition leads to activation of proximal tubular epithelial cells. Our preliminary findings implicate a glomerulotubular cross talk with mediators released from the mesangium contributing to the pathogenesis of tubulointerstitial damage in IgAN. We have also found the expression of angiotensin II subtype-1 receptor or angiotensin II subtype-2 receptor in proximal tubular epithelial cells differs from that of mesangial cells. One potential therapeutic approach is to counterbalance the growth-stimulatory effects of angiotensin II through subtype-1 receptor in tubular epithelial cells by subtype-2 receptor-mediated apoptosis and growth inhibition. These novel findings may provide clinicians new therapeutic approach for selective blockade of the RAS in IgAN.     

Detection of SARS coronavirus in patients with suspected SARS

Cases of severe acute respiratory syndrome (SARS) were investigated for SARS coronavirus (SARS-CoV) through RNA tests, serologic response, and viral culture. Of 537 specimens from patients in whom SARS was clinically diagnosed, 332 (60%) had SARS-CoV RNA in one or more clinical specimens, compared with 1 (0.3%) of 332 samples from controls. Of 417 patients with clinical SARS from whom paired serum samples were available, 92% had an antibody response. Rates of viral RNA positivity increased progressively and peaked at day 11 after onset of illness. Although viral RNA remained detectable in respiratory secretions and stool and urine specimens for >30 days in some patients, virus could not be cultured after week 3 of illness. Nasopharyngeal aspirates, throat swabs, or sputum samples were the most useful clinical specimens in the first 5 days of illness, but later in the illness viral RNA could be detected more readily in stool specimens.     

Minimal risk as an international ethical standard in research

Classifying research proposals by risk of harm is fundamental to the approval process and the most pivotal risk category in most regulations is that of "minimal risk." If studies have no more than a minimal risk, for example, a nearly worldwide consensus exists that review boards may sometimes: (1) expedite review, (2) waive or modify some or all elements of informed consent, or (3) enroll vulnerable subjects including healthy children, incapacitated persons and prisoners even if studies do not hold out direct benefits to them. The moral and social purposes behind this threshold are discussed along with relevant views from the National Commission, NBAC, NHRPAC, Grimes v. Kennedy Krieger Institute, The Nuremberg Code, and The WMA's Declaration of Helsinki. Representative policies from Australia, Canada, South Africa, the U.S., and CIOMS are reviewed revealing different understandings of this sorting threshold. Six of nine frequently cited interpretations of "minimal risk" are untenable. The "absolute" interpretation of the "routine examination" standard is defended as best.