Search PubMed⌕ Search

Biomedical subjects

J D Clemens

Publications and source records attributed to J D Clemens.

At least 37 records · Page 2Linked to original sources

Epidemiology of postshigellosis persistent diarrhea in young children.

BACKGROUND: Dysentery accounts for 20% of the 4.6 million diarrhea-associated deaths among children in developing countries, with the risk from death in dysenteric persistent diarrhea 10-fold higher than that in acute dysentery. Although Shigella accounts for the majority of dysenteric episodes, very little is known about the epidemiology of postshigellosis persistent diarrhea. METHODS: Rural Bangladeshi children younger than 5 years of age (n = 1,756) were followed for 1 month after exposure to sentinel cases of Shigella dysentery. The likelihood of an acute diarrheal episode becoming persistent was assessed. RESULTS: Diarrhea caused by Shigella was significantly associated with an increased risk of persistent diarrhea (age-adjusted relative risk, 1.83; 95% confidence interval, 1.19 to 2.81). Despite the use of nalidixic acid in dysenteric episodes, persistent diarrhea occurred in 23% of children with shigellosis. Infection by multiply antibiotic-resistant Shigella isolates (age-adjusted relative risk, 3.76; 95% confidence interval, 1.51 to 9.36) and occurrence of shigellosis during infancy were observed to be risk factors for initiation of Shigella diarrhea persistence. However, 88% of the persistent shigellosis episodes occurred in older children, 50% were associated with nondysenteric shigellosis and 79% were caused by Shigella species other than Shigella dysenteriae 1. CONCLUSIONS: These data demonstrate the importance of Shigella as a cause of persistent diarrhea and indicate that strategies to prevent postshigellosis persistent diarrhea must be broad-based, with a focus on older children as well as infants, management of nondysenteric as well as dysenteric disease and prevention of diarrhea caused by multiple Shigella species.

Bangladesh↗

Induction of systemic antifimbria and antitoxin antibody responses in Egyptian children and adults by an oral, killed enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine.

We assessed serologic responses to an oral, killed whole-cell enterotoxigenic Escherichia coli plus cholera toxin B-subunit (ETEC-rCTB) vaccine in 73 Egyptian adults, 105 schoolchildren, and 93 preschool children. Each subject received two doses of vaccine or placebo 2 weeks apart, giving blood before immunization and 7 days after each dose. Plasma antibodies to rCTB and four vaccine-shared colonization factors (CFs) were measured by enzyme-linked immunosorbent assay. Immunoglobulin A (IgA) antibodies to rCTB and CFA/I were measured in all subjects, and those against CS1, CS2, and CS4 were measured in all children plus a subset of 33 adults. IgG antibodies to these five antigens were measured in a subset of 30 to 33 subjects in each cohort. Seroconversion was defined as a >2-fold increase in titer after vaccination. IgA and IgG seroconversion to rCTB was observed in 94 to 95% of adult vaccinees, with titer increases as robust as those previously reported for these two pediatric cohorts. The proportion showing IgA seroconversion to each CF antigen among vaccinated children (range, 70 to 96%) and adults (31 to 69%), as well as IgG seroconversion in children (44 to 75%) and adults (25 to 81%), was significantly higher than the corresponding proportion in placebo recipients, except for IgA responses to CS2 in adults. IgA anti-CF titers peaked after one dose in children, whereas in all age groups IgG antibodies rose incrementally after each dose. Independently, both preimmunization IgA titer and age were inversely related to the magnitude of IgA responses. In conclusion, serologic responses to the ETEC-rCTB vaccine may serve as practical immune outcome measures in future pediatric trials in areas where ETEC is endemic.

Administration, Oral↗

Prevalence and predictors of immunization among inner-city infants: a birth cohort study.

CONTEXT: Although the proportion of US children who are appropriately immunized increased dramatically in the past decade, rates remain suboptimal among low-income, inner-city youth. Timely initiation of immunization is an important predictor of immunization status later in childhood; however, prospective studies identifying predictors of initiation are lacking. OBJECTIVES: The objectives of this study were to: 1) describe immunization patterns in a cohort of infants born to predominantly low-income, inner-city mothers; 2) identify determinants, as measured at birth, of immunization status at 3 and 7 months of age; and 3) identify determinants of continuation of immunization among those who initiate immunization by 3 months of age. DESIGN: Prospective, birth cohort study. METHODS: Maternal/infant dyads were systematically selected from 3 District of Columbia hospitals between August 1995 and September 1996. Three hundred sixty-nine mothers were interviewed shortly after delivery, at 3 to 7 months postpartum, and at 7 to 12 months postpartum. Medical records were reviewed at all reported sites of care for 324 (88%) infants. Vaccinations assessed included diphtheria, tetanus, and pertussis; polio; and Haemophilus influenzae type B. Multivariate logistic regression analyses were used to determine factors associated with immunization status of infants at 3 and 7 months of age. RESULTS: At 3 months of age, 75% of infants were up-to-date (UTD) versus only 41% at 7 months. In adjusted analyses, baseline factors associated with being UTD at 3 months included enrollment in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) during pregnancy, intention to breastfeed, and presence of the infant's grandmother in the household. Infants were less likely to be UTD if their mothers perceived higher barriers to immunization. Baseline factors associated with being UTD at 7 months included lower birth order and maternal employment. Among the subset of infants who were UTD at 3 months, only 53% remained UTD at 7 months. Factors measured at the first follow-up interview that were associated with continuation of immunization at 7 months included maternal employment and lower perceived barriers. CONCLUSIONS: Immunization rates during the first 7 months of life were low in this inner-city population. Factors associated with immunization status that are potentially amenable to change included perceived barriers to immunization and enrollment in WIC during pregnancy.

Adult↗

Astrovirus diarrhea in Egyptian children.

This study describes the epidemiology of astrovirus diarrhea among a population-based cohort of 397 children aged <3 years residing in rural Egypt from 1995 to 1998. The age-specific incidence rates of astrovirus diarrheal episodes per person-year were 0.38 for infants aged <6 months, 0.40 for those aged 6-11 months, 0.16 for those aged 12-23 months, and 0.05 for those aged 24-35 months. The overall incidence rate of astrovirus diarrhea was the same as that of rotavirus diarrhea, 0.19 episodes per person-year. Astrovirus infection was pathogenic and associated with severe dehydration in 17% of the cases. The most frequent serotype was HAstV-1, and, in order of decreasing frequency, HAstV-5, HAstV-8 and HAstV-3, HAstV-6, HAstV-4, and HAstV-2. In determining whether astrovirus diarrhea was associated with a reduced incidence of subsequent disease, there was evidence to suggest HAstV-1 homotypic immunity but not heterotypic immunity. Because we observed 38% of the incidence of astrovirus diarrhea to occur in infants aged <6 months, a candidate astrovirus vaccine would have to confer immunity very early in life.

Astroviridae Infections↗

Bone mineral density and serum levels of aminoterminal propeptides and cross-linked N-telopeptides of type I collagen in elderly men.

Serum levels of aminoterminal extension propeptides (PINP), the carboxyterminal telopeptide (ICTP), and the cross-linked N-telopeptides (NTx) of type I collagen were determined in 78 healthy, elderly men aged 76 +/- 5 years in 1993 and 1996 and compared with bone mineral density (BMD) measurements of their lumbar spine, femoral neck, and total body regions made using dual X-ray absorptiometry. Compared with 11 men who had normal lumbar spine (SBMD) and femoral neck BMD (NBMD), 13 of the subjects with SBMD and NBMD classified as osteopenic by t-score criterion had higher mean serum levels of PINP and alkaline phosphatase activity, but these increases were not statistically significant at the 95% confidence interval. In osteopenic men, a correlation between SBMD and NTx was detected (r = -0.66, p = 0.01). Within the entire population, the serum NTx level correlated with NBMD (r = -0.26, p < 0.05) and PINP (r = +0.63, p < 0.0001), and the change in the circulating concentration of PINP over the 3 year interval correlated with the magnitude of change in total body BMD (r = -0.28, p = 0.02), NBMD (r = -0.24, p = 0.05), and SBMD (r = -0.36, p = 0. 03) as well as with the change in serum NTx levels (r = 0.43, p < 0. 001). The change in the circulating ICTP level was also related to the change in NBMD (r = -0.24, p = 0.01). Together, weight and the serum PINP level accounted for 25% of total body BMD variance in elderly men. These results indicate that larger populations of men and women should be screened over longer time intervals to explore the value of serial measurement of serum collagen metabolites in predicting bone loss in the spine and hip.

Aged↗

Seroepidemiology of Helicobacter pylori infection in a population of Egyptian children.

BACKGROUND: To describe the seroepidemiology of Helicobacter pylori infection in a population of Egyptian children under 3 years. METHODS: A cohort of children under 36 months, residing in Abu Homos, Egypt, were visited at home twice weekly. Information regarding the child's breastfeeding status was obtained, and periodic anthropometric and household hygiene surveys were performed. In June 1997, a serosurvey was conducted on 187 study participants over 6 months old. The serosurvey was repeated in October 1997. All sera were tested for IgG antibodies to H. pylori. RESULTS: The June prevalence of H. pylori infection was 10%, and the incidence from June to October was 15%. Between June and October, 8 (42%) of 19 children that were positive for H. pylori infection seroreverted to negative. All seroreversions occurred in children 6-17 months. Other than age, no sociodemographic or environmental factor was significantly associated with incident H. pylori infection. There was no significant differences in the weight-for-age, weight-for-height, and height-for-age z-scores between children with and without prevalent H. pylori infection. CONCLUSIONS: Infection with H. pylori is common in Egyptian children under 3 years old and is not associated with malnutrition. No predictors for H. pylori infection were found. Our preliminary evidence for transient H. pylori infections in young children needs to be confirmed in a prospective cohort study, and predictors for persistent infection should be sought, since only these may be relevant to the known sequellae of infection.

Anthropometry↗

Maternal serum paraxanthine, a caffeine metabolite, and the risk of spontaneous abortion.

BACKGROUND: Whether the consumption of caffeine during pregnancy increases the risk of spontaneous abortion is controversial. Prior studies have determined caffeine consumption by questionnaire. We used a biologic marker, such as serum paraxanthine, a metabolite of caffeine, to measure the dose of caffeine. METHODS: In a nested case-control study, we measured serum paraxanthine in 591 women who had spontaneous abortions at less than 140 days' gestation and in 2558 matched women from the same clinic who gave birth to live infants at 28 weeks' gestation or later and who had serum drawn on the same day of gestation as the women who had abortions. The women were enrolled in the Collaborative Perinatal Project during the period from 1959 to 1966, and serum paraxanthine was measured over 30 years later. RESULTS: A total of 487 women who had spontaneous abortions (82 percent) and 2087 controls (82 percent) had quantifiable serum paraxanthine concentrations. However, the mean serum paraxanthine concentration was higher in the women who had spontaneous abortions than in the controls (752 vs. 583 ng per milliliter, P<0.001). The odds ratio for spontaneous abortion was not significantly elevated in the women who had serum paraxanthine concentrations of 1845 ng per milliliter or lower, corresponding to the 95th percentile of the matched women. However, the adjusted odds ratio for spontaneous abortion among women with serum paraxanthine concentrations higher than 1845 ng per milliliter, as compared with women who had concentrations below 50 ng per milliliter, was 1.9 (95 percent confidence interval, 1.2 to 2.8). CONCLUSIONS: Only extremely high serum paraxanthine concentrations are associated with spontaneous abortion. This suggests that moderate consumption of caffeine is unlikely to increase the risk of spontaneous abortion.

Abortion, Spontaneous↗

Epidemiology of rotavirus diarrhea in Egyptian children and implications for disease control.

Reliable epidemiologic data are essential for formulating effective policy to control rotavirus disease through immunization. The objective of this study was to describe the epidemiology of rotavirus diarrhea in a population-based cohort of children under 3 years of age residing in Abu Homos, Egypt, in 1995-1996. Rotavirus diarrhea incidence rates (episodes per person-year) were 0.13 for infants aged <6 months, 0.61 for those aged 6-11 months, 0.17 for those aged 12-23 months, and 0.15 for those aged 24-35 months. Fifty-six percent of children with rotavirus diarrhea had clinical dehydration; 90% of rotavirus diarrheal episodes occurred between July and November. In infants under 1 year of age, receipt of breast milk was associated with a lower incidence of rotavirus diarrhea. No other sociodemographic or environmental factor was found to be significantly associated with rotavirus diarrhea. Of 46 rotavirus isolates with strains identified, 41 (89%) were G serotypes 1 and 2. Rotavirus diarrhea was a major cause of morbidity in this cohort. Promotion of breastfeeding may exert a protective effect in young infants in this setting, but improvements in water and sanitation are unlikely to be effective preventive measures. The use of effective immunization against rotavirus in early infancy should be considered a public health priority.

Age Distribution↗

Typhoid fever in children aged less than 5 years.

BACKGROUND: Calculation of the incidence of typhoid fever during preschool years is important to define the optimum age of immunisation and the choice of vaccines for public-health programmes in developing countries. Hospital-based studies have suggested that children younger than 5 years do not need vaccination against typhoid fever, but this view needs to be re-examined in community-based longitudinal studies. We undertook a prospective follow-up study of residents of a low-income urban area of Delhi, India, with active surveillance for case detection. METHODS: A baseline census was undertaken in 1995. Between Nov 1, 1995, and Oct 31, 1996, we visited 8172 residents of 1820 households in Kalkaji, Delhi, twice weekly to detect febrile cases. Blood samples were obtained from febrile patients, and those who tested positive for Salmonella typhi were treated with ciprofloxacin. FINDINGS: 63 culture-positive typhoid fever cases were detected. Of these, 28 (44%) were in children aged under 5 years. The incidence rate of typhoid per 1000 person-years was 27.3 at age under 5 years, 11.7 at 5-19 years, and 1.1 between 19 and 40 years. The difference in the incidence of typhoid fever between those under 5 years and those aged 5-19 years (15.6 per 1000 person-years [95% CI 4.7-26.5]), and those aged 19-40 years (26.2 [16.0-36.3]) was significant (p<0.001 for both). The difference between the incidence of typhoid at 5-19 years and the incidence at 19-40 years was also significant (10.6 [6.3-14.8], p<0.001). Morbidity in those under 5 and in older people was similar in terms of duration of fever, signs and symptoms, and need for hospital admission. INTERPRETATION: Our findings challenge the common view that typhoid fever is a disorder of school-age children and of adults. Typhoid is a common and significant cause of morbidity between 1 and 5 years of age. The optimum age of typhoid immunisation and the choice of vaccines needs to be reassessed.

Adolescent↗

Prostacyclin and thromboxane changes predating clinical onset of preeclampsia: a multicenter prospective study.

CONTEXT: An imbalance in vasodilating (prostacyclin [PGI2]) and vasoconstricting (thromboxane A2 [TxA2]) eicosanoids may be important in preeclampsia, but prospective data from large studies needed to resolve this issue are lacking. Because most trials using aspirin to reduce TxA2 production have failed to prevent preeclampsia, it is critical to determine whether eicosanoid changes occur before the onset of clinical disease or are secondary to clinical manifestations of preeclampsia. OBJECTIVE: To determine whether PGI2 or TxA2 changes occur before onset of clinical signs of preeclampsia. DESIGN, SETTING, AND PARTICIPANTS: Multicenter prospective study from 1992 to 1995 of subjects from the placebo arm of the Calcium for Preeclampsia Prevention Trial. Women who developed preeclampsia (n = 134) were compared with matched normotensive control women (n = 139). MAIN OUTCOME MEASURES: Excretion of urinary metabolites of PGI2 (PGI-M) and TxA2 (Tx-M) as measured from timed urine collections obtained prospectively before 22 weeks', between 26 and 29 weeks', and at 36 weeks' gestation. RESULTS: Women who developed preeclampsia had significantly lower PGI-M levels throughout pregnancy, even at 13 to 16 weeks' gestation (long before the onset of clinical disease); their gestational age-adjusted levels were 17% lower than those of controls (95% confidence interval [CI], 6%-27%; P=.005). The Tx-M levels of preeclamptic women were not significantly higher overall (9% higher than those of controls; 95% CI, -3% to 23%; P=.14). The ratio of Tx-M to PGI-M, used to express relative vasoconstricting vs vasodilating effects, was 24% higher (95% CI, 6%-45%) in preeclamptic women throughout pregnancy (P=.007). CONCLUSIONS: Our results show that reduced PGI2 production, but not increased TxA2 production, occurs many months before clinical onset of preeclampsia. Aspirin trials may have failed because an increase in thromboxane production is not the initial anomaly. Future interventions should make correcting prostacyclin deficiency a major part of the strategy to balance the abnormal vasoconstrictor-vasodilator ratio present in preeclampsia.

6-Ketoprostaglandin F1 alpha↗

Characterization of unusual G8 rotavirus strains isolated from Egyptian children.

We report the first detection of P[14], G8 rotaviruses isolated in Egypt from the stool of children participating in a 3 year study of rotavirus epidemiology. Two strains, EGY1850 and EGY2295, were characterized by a serotyping enzyme immunoassay (EIA), virus neutralization, and sequence analysis of the genes encoding VP7 and the VP8* portion of the VP4 gene. These two strains shared a high level of homology of their VP7s (87.8% nucleotide [nt], 97.2% amino acid [aa]) and VP4s (89.6% nt, 97.1% aa) and had the highest VP7 identity to serotype G8 (> 82% nt, > 92% aa) and VP4 identity to genotype P[14] (> or = 81% nt, > 91% aa) strains. Serological results with a VP7 G8-specific and VP4 P[14]-specific neutralizing monoclonal antibodies supported the genetic classification of EGY1850 and EGY2295 as P[14], G8. Genogroup analysis supports earlier findings that human G8 rotaviruses may be genetically related to bovine rotaviruses. These findings demonstrate that our understanding of the geographic distribution of rotavirus strains is incomplete, emphasize the need to monitor rotavirus serotypes, and extend the known distribution of serotype G8 and genotype P[14] strains in Africa.

Animals↗

Oral, inactivated, whole cell enterotoxigenic Escherichia coli plus cholera toxin B subunit vaccine: results of the initial evaluation in children. PRIDE Study Group.

Two randomized, double-blinded trials assessed the safety and immunogenicity of an oral, killed enterotoxigenic Escherichia coli (ETEC) plus cholera toxin B subunit vaccine in Egyptian children. Two doses of vaccine or E. coli K-12 were given 2 weeks apart to 105 6- to 12-year-olds and 97 2- to 5-year-olds. Safety was monitored for 3 days after each dose. Blood was collected before immunization and 7 days after each dose to measure immune responses. Few children reported postdosing symptoms, with no differences in the frequency of symptoms between treatment groups. Most vaccinees had an IgA antibody-secreting cell response against colonization factor antigen I (100%, 6-12 years; 95%, 2-5 years), coli surface antigen 2 (92%, 6-12 years; 83%, 2-5 years), and coli surface antigen 4 (93%, 6-12 years). Vaccination evoked a >/=4-fold rise in antitoxic IgA and IgG titers in 93% and 81% of children, respectively. In conclusion, the oral ETEC vaccine was safe and immunogenic in 2- to 12-year-old children, justifying further evaluation in infants.

Administration, Oral↗

Epidemiology of enterotoxigenic Escherichia coli diarrhea in a pediatric cohort in a periurban area of lower Egypt.

Enterotoxigenic Escherichia coli (ETEC) are diverse pathogens that express heat-labile (LT) and/or heat-stable (ST) enterotoxins, yet little is known about whether epidemiologic patterns of pediatric ETEC diarrhea vary by the expressed ETEC toxin phenotype. In total, 242 Egyptian children aged <3 years were prospectively followed in 1993-1995. ETEC episodes were detected during twice-weekly home visits, and asymptomatic ETEC excretion was identified from monthly cross-sectional surveys. ETEC episodes were 0.6 per child-year. ST-only ETEC was 2.6 times (P<.001) more common in warmer than cooler months, while LT-only ETEC showed no seasonal variation. Ownership of a household sanitary latrine, but not breast-feeding, was associated with a lower risk of both enterotoxin phenotypes. Coexpression of a colonization factor by LT- or ST-only ETEC strengthened the association with diarrhea. These findings indicate that the epidemiologic patterns of LT-only and ST-only ETEC are not identical and that disease interventions should include improved household sanitation.

Cohort Studies↗

Phenotypic diversity of enterotoxigenic Escherichia coli strains from a community-based study of pediatric diarrhea in periurban Egypt.

No past studies of diarrhea in children of the Middle East have examined in detail the phenotypes of enterotoxigenic Escherichia coli (ETEC) strains, which are important pathogens in this setting. During a prospective study conducted from November 1993 to September 1995 with 242 children under 3 years of age with diarrhea living near Alexandria, Egypt, 125 episodes of diarrhea were positive for ETEC. ETEC strains were available for 98 of these episodes, from which 100 ETEC strains were selected and characterized on the basis of enterotoxins, colonization factors (CFs), and O:H serotypes. Of these representative isolates, 57 produced heat-stable toxin (ST) only, 34 produced heat-labile toxin (LT) only, and 9 produced both LT and ST. Twenty-three ETEC strains expressed a CF, with the specific factors being CF antigen IV (CFA/IV; 10 of 23; 43%), CFA/II (5 of 23; 22%), CFA/I (3 of 23; 13%), PCFO166 (3 of 23; 13%), and CS7 (2 of 23; 9%). No ETEC strains appeared to express CFA/III, CS17, or PCFO159. Among the 100 ETEC strains, 47 O groups and 20 H groups were represented, with 59 O:H serotypes. The most common O serogroups were O159 (13 strains) and O43 (10 strains). O148 and O21 were each detected in five individual strains, O7 and O56 were each detected in four individual strains, O73, O20, O86, and O114 were each detected in three individual strains, and O23, O78, O91, O103, O128, and O132 were each detected in two individual strains. The most common H serogroups were H4 (16 strains), 12 of which were of serogroup O159; H2 (9 strains), all of which were O43; H18 (6 strains); H30 (6 strains); and H28 (5 strains); strains of the last three H serogroups were all O148. Cumulatively, our results suggest a high degree of clonal diversity of disease-associated ETEC strains in this region. As a low percentage of these strains expressed a CF, it remains possible that other adhesins for which we either did not assay or that are as yet undiscovered are prevalent in this region. Our findings point out some potential barriers to effective immunization against ETEC diarrhea in this population and emphasize the need to identify additional protective antigens commonly expressed by ETEC for inclusion in future vaccine candidates.

Bacterial Proteins↗

Global burden of Shigella infections: implications for vaccine development and implementation of control strategies.

Few studies provide data on the global morbidity and mortality caused by infection with Shigella spp.; such estimates are needed, however, to plan strategies of prevention and treatment. Here we report the results of a review of the literature published between 1966 and 1997 on Shigella infection. The data obtained permit calculation of the number of cases of Shigella infection and the associated mortality occurring worldwide each year, by age, and (as a proxy for disease severity) by clinical category, i.e. mild cases remaining at home, moderate cases requiring outpatient care, and severe cases demanding hospitalization. A sensitivity analysis was performed to estimate the high and low range of morbid and fatal cases in each category. Finally, the frequency distribution of Shigella infection, by serogroup and serotype and by region of the world, was determined. The annual number of Shigella episodes throughout the world was estimated to be 164.7 million, of which 163.2 million were in developing countries (with 1.1 million deaths) and 1.5 million in industrialized countries. A total of 69% of all episodes and 61% of all deaths attributable to shigellosis involved children under 5 years of age. The median percentages of isolates of S. flexneri, S. sonnei, S. boydii, and S. dysenteriae were, respectively, 60%, 15%, 6%, and 6% (30% of S. dysenteriae cases were type 1) in developing countries; and 16%, 77%, 2%, and 1% in industrialized countries. In developing countries, the predominant serotype of S. flexneri is 2a, followed by 1b, 3a, 4a, and 6. In industrialized countries, most isolates are S. flexneri 2a or other unspecified type 2 strains. Shigellosis, which continues to have an important global impact, cannot be adequately controlled with the existing prevention and treatment measures. Innovative strategies, including development of vaccines against the most common serotypes, could provide substantial benefits.

Adolescent↗

Urinary cross-linked N-telopeptides of type I collagen and bone metabolic diseases.

OBJECTIVE: To evaluate the type I collagen cross-linked N-telopeptide (NTx) levels in human urine as an indicator of bone resorption rate in different ages, sex and in bone metabolic diseases. METHODS: Urinary NTx was determined by immunoassay in 591 Beijing healthy subjects aged from 0 to 86 years and 379 patients with bone metabolic diseases. RESULTS: The levels of urinary NTx were significantly higher in children than in adults (P < 0.001) and higher in boys than in girls (P < 0.01) and increased 1.4-2.2 times in postmenopausal females than in men and premenopausal women. Urine NTx had a positive linear correlation with urine HOP/Cr (r = 0.778, P < 0.01) and Ca/Cr ratio (r = 0.320, P < 0.01), and a negative linear correlation with age (r = -0.523, P < 0.01) and lumbar spine BMD (r = -0.426, P < 0.01). The levels of urine NTx increased for 3.6 times in pregnancy, 1.5 times in osteoporosis, 1.9 times in fragility fracture, 3.6 times in chronic renal failure, 2.1 times in rickets and 7.2 times in multiple myeloma compared to age matched controls. CONCLUSIONS: NTx in urine is a specific and sensitive indicator of bone resorption and is able to distinguish normal premenopause from late osteoporotic patients. NTx could be used as diagnostic information about metabolic bone diseases, and to monitor antiresorptive therapy.

Adolescent↗

Serum cotinine concentration and self-reported smoking during pregnancy.

Although during pregnancy there is a better correlation between maternal serum cotinine concentration and adverse outcome than between self-reported smoking and such an outcome, few studies of pregnancy have measured cotinine concentration to determine how much a woman smokes. This study assessed the accuracy of self-reported smoking during pregnancy by performing serum cotinine assays on 448 women registered in the Collaborative Perinatal Project (1959-1966). Based on the assumption that a serum cotinine concentration of >10 ng/ml represented active smoking, 94.9% of women who denied smoking and 87.0% of women who stated that they smoked (kappa=0.83) reported their status accurately. Among smokers, the correlation coefficient between cotinine concentration and number of cigarettes smoked per day was 0.44. Serum cotinine concentration correlated more strongly than self-reported smoking with infant birth weight (r=0.246 vs. 0.200). In conclusion, this study showed that pregnant women accurately reported whether they smoked, but cotinine concentration was a better measure than self-report of the actual tobacco dose received.

Adult↗

Estimation of vaccine efficacy in the presence of waning: application to cholera vaccines.

The authors present a nonparametric method for estimating vaccine efficacy as a smooth function of time from vaccine trials. Use of the method requires a minimum of assumptions. Estimation is based on the smoothed case hazard rate ratio comparing the vaccinated with the unvaccinated. The estimation procedure allows investigators to assess time-varying changes in vaccine-induced protection, such as those produced by waning and boosting. The authors use the method to reanalyze data from a vaccine trial of two cholera vaccines in rural Bangladesh. This analysis reveals the differential protection and waning effects for the vaccines as a function of biotype and age.

Adolescent↗