Efficacy and safety of nonsteroidal antiinflammatory drugs for cancer pain: a meta-analysis.

PURPOSE: To assess the efficacy and safety of nonsteroidal antiinflammatory drugs (NSAIDs) in the treatment of cancer pain by meta-analyses of the published randomized control trials (RCTs). PATIENTS AND METHODS: Twenty-five studies met inclusion criteria for analysis. Of these, 13 tested a single-dose effect, nine multiple-dose effects, and three both single- and multiple-dose effects of 16 different NSAIDs in a total of 1,545 patients. Baseline pain intensity (when provided) of moderate or higher was indicated in 81% of patients. RESULTS: Single-dose NSAID studies found greater analgesic efficacy than placebo, with rough equivalence to 5 to 10 mg of intramuscular morphine. Pain scores differed insignificantly for aspirin versus three other NSAIDs. Analgesic responses to low- and high-dose NSAIDs suggested a dose-response relationship, but this was not statistically significant. Recommended and supramaximal single doses of three NSAIDs produced comparable changes in pain scores, which indicates a ceiling analgesic effect. Common side effects included upper gastrointestinal symptoms, dizziness, and drowsiness. The incidence of side effects showed a trend to increase with dose, without a ceiling effect, and to increase with multiple doses. Single or multiple doses of weak opioids (WO) alone or in combination (WO/C) with nonopioid analgesics did not produce greater analgesia than NSAIDs alone. Single doses of WO/C analgesics produced more side effects than NSAIDs alone, although both side effect incidence and patient dropout rates were equal when multiple doses were administered. CONCLUSION: These findings question whether the traditional World Health Organization (WHO) second analgesic step (addition of a weak opioid when pain is inadequately treated by a nonopioid analgesic alone) is warranted. A lack of comparable studies precluded testing the hypothesis that NSAIDs are particularly effective for malignant bone pain.

Long-term memory of body weight and past weight satisfaction: a longitudinal follow-up study.

Recalled body weight and self-reported current weight were validated in a longitudinal study population by comparing recalls at 50 y to actual measures taken at ages 18, 30, 40, and 50 y. Recalled body weights were also compared with reported desired weights at these same ages. Self-reported weights at 50 y were equally accurate for both males and females; the mean reporting underestimate was -1.98 kg for males and -1.86 kg for females. Males' self reports at age 50 y were influenced by years of education (P less than 0.005) and current body size (P less than 0.0001) whereas females' were not. Correlations between recall of past weights and measured weights ranged from r = 0.87 at 18 y to 0.95 at 40 y. Recalls of past body weight were not significantly influenced by the passage of time, the number of years of education, or the accuracy of current weight reports. Current body size (wt/ht2) was significantly associated with life-time weight dissatisfaction in both sexes (P less than 0.0005).

Weight concerns, weight control behaviors, and smoking initiation.

OBJECTIVE: To examine the cross-sectional relationships between weight concerns, weight control behaviors, and initiation of tobacco use among youths. STUDY DESIGN: Smoking status, weight concerns, and weight control behaviors were assessed in a cross-sectional sample of 16 862 children, 9 to 14 years of age, in 1996. Logistic regression was used to examine the relationship between weight concerns, weight control behaviors, and early stages of smoking initiation (precontemplation, contemplation, and experimentation). All analyses were adjusted for age, body mass index, and known predictors of initiation. RESULTS: Approximately 9% of participants had experimented with cigarettes, and 6% were contemplating cigarette smoking. Contemplation of tobacco use was associated with misperception of being overweight (boys: odds ratio [OR], 1.65; 95% confidence interval [CI], 1.10-2.48), unhappiness with appearance (girls: OR, 2.05; 95% CI, 1.48-2.84; boys: OR, 1.60; 95% CI, 1.05-2. 42), and a tendency to change eating patterns around peers (girls: OR, 2.87; 95% CI, 2.28-3.62; boys: OR, 1.83; 95% CI, 1.25-2.66). Experimentation with cigarettes was associated with daily exercise to control weight among boys (OR, 1.92; 95% CI, 1.07-3.43) and with monthly purging (OR, 2.54; 95% CI, 1.27-5.07) and daily dieting among girls (OR, 1.79; 95% CI, 1.09-2.96). CONCLUSIONS: Our findings suggest that, among both girls and boys, contemplation of smoking is positively related to weight concerns. Experimentation seems to be positively related to weight control behaviors. It is important for both pediatricians and comprehensive school health programs to address healthy methods of weight maintenance and to dispel the notion of tobacco use as a method of weight control.

The efficacy of bacillus Calmette-Guérin vaccination of newborns and infants in the prevention of tuberculosis: meta-analyses of the published literature.

OBJECTIVE: To quantify the efficacy of vaccination of infants with bacillus Calmette-Guérin (BCG) against tuberculosis. DATA SOURCES: MEDLINE with index terms BCG vaccine, tuberculosis, and human; lists of all known studies provided by experts at the Centers for Disease Control and Prevention, the World Health Organization, and other organizations. STUDY SELECTION: A total of 1264 articles and abstracts were reviewed for details on BCG vaccination, the availability of concurrent vaccinated and unvaccinated groups, and a tuberculosis outcome. Seventy articles were reviewed in depth for method of vaccine allocation used to create comparable groups, age at vaccination of study participants, comparability of surveillance and follow-up of recipient and concurrent control groups in trials, an appropriately defined control group in case-control studies, and outcome measures (tuberculosis cases and/or deaths). Five prospective trials and eleven case-control studies of vaccination during infancy were included in the present analyses. DATA EXTRACTION: We recorded study design, age range of study population, number of patients enrolled, efficacy of vaccine, location of the study, and a series of items to assess the potential for bias in study design, follow-up, and diagnosis. We extracted or computed vaccine efficacy by years since vaccination wherever possible. At least two readers independently extracted data and evaluated data validity. DATA SYNTHESIS: The relative risk (RR) or odds ratio (OR) for tuberculosis in vaccinated versus unvaccinated infants was the measure of vaccine efficacy analyzed. A random-effects method estimated a weighted average RR or OR from data extracted from the trials and case-control studies. The protective effect was then computed by 1-RR or 1-OR. Overall, the protective effect of vaccination against cases of tuberculosis was 0.74 (95% confidence interval [95% CI], 0.62 to 0.83) when estimated from four randomized controlled trials, and 0.52 (95% CI, 0.38 to 0.64) when estimated from nine case-control studies. Five trials reporting deaths from tuberculosis showed a BCG protective effect of 0.65 (95% CI, 0.12 to 0.86), five studies reporting on meningitis showed a protective effect of 0.64 (95% CI, 0.30 to 0.82), and three studies of disseminated tuberculosis showed a protective effect of 0.78 (95% CI, 0.58 to 0.88). Three case-control studies included separate results for laboratory-confirmed cases of tuberculosis. These studies documented a protective effect of 0.83 (95% CI, 0.58 to 0.93). In a random-effects regression model of the nine case-control studies, study validity score explained 15% of the heterogeneity among study-estimated protective effects, suggesting that better studies reported greater efficacy. Three trials and six case-control studies provided some age-specific information that allowed us to examine the duration of BCG efficacy. Most of this evidence suggested that BCG efficacy may persist through 10 years after infant vaccination. CONCLUSION: BCG vaccination of newborns and infants significantly reduces the risk of tuberculosis--by over 50%, on average. Protection has been observed across many populations, study designs, and forms of tuberculosis. Rates of protection against cases that are confirmed by laboratory tests, reflecting reduced error in disease classification and consequently more accurate estimates of BCG efficacy, are highest at 83%.

Effects of passive smoking on health of children.

Analysis of data on the effects of passive smoking obtained in preadolescent children from the Harvard Six-Cities Study demonstrates an exposure-response relationship between the number of smokers in the household and the reporting rates for doctor-diagnosed respiratory illness before age 2, history of bronchitis, wheeze most days and nights apart from colds, and a composite of symptoms defined as the lower respiratory index. Similarly, when only the amount currently smoked by the mother was used, the data indicated a relatively uniform increase in each of the reported diseases and symptoms. FEV1 was lower in children with smoking mothers compared to children of nonsmoking mothers. Rate of increases in FEV1 after adjusting for normal growth was significantly smaller in children of smoking mothers and was related also to amount smoked. Notably the effect on level of FVC was not seen and this finding, consistent in several studies, remains unexplained. Although children of smoking mothers were shorter on the average than children of nonsmoking mothers, no on-going passive smoking effect on height growth can be ascertained. All these differences are small and their medical significance remains to be defined.

Passive smoking and height growth of preadolescent children.

The attained height and height growth rate of 9273 children participating in a longitudinal study of the health effects of air pollutants were analysed to assess the association between passive exposure to cigarette smoke and physical growth between 6 and 11 years of age. Children were measured annually for 2 to 6 years. Each height measurement was adjusted for sex and age by the NCHS anthropometric standards. Each child's adjusted heights were then re-expressed as level of attained height and growth rate. Attained height exhibited a dose-response relationship with amount of current maternal cigarette smoking (p less than 0.001). Children whose mothers smoked ten or more cigarettes daily were approximately 0.65 cm shorter than children of non-smokers, while children whose mothers smoked between 1 and 9 cigarettes per day were 0.45 cm shorter. However, passive smoking was not correlated with the child's growth rate. Exposure to paternal smoking was not significantly associated with height, either in terms of attained level or growth rate. These results indicate that passive smoking in the 6- to 11-year-old child does not continue to affect the growth rate of height and that the observed association between attained height and maternal smoking behaviour is due to exposures in utero and/or during infancy and the preschool years.

Relation of peer and media influences to the development of purging behaviors among preadolescent and adolescent girls.

OBJECTIVE: To assess prospectively the relation of peer and media influences on the risk of development of purging behaviors. DESIGN: Prospective cohort study. SETTING: One year follow-up of 6982 girls aged 9 to 14 years in 1996 who completed questionnaires in 1996 and 1997 and reported in 1996 that they did not use vomiting or laxatives to control weight. MAIN OUTCOME MEASURE: Self-report of using vomiting or laxatives at least monthly to control weight. RESULTS: During 1 year of follow-up, 74 girls began using vomiting or laxatives at least monthly to control weight. Tanner stage of pubic hair development was predictive of beginning to purge (odds ratio [OR] = 1.8; 95% confidence interval [CI], 1.3-2.4). Independent of age and Tanner stage of pubic hair development, importance of thinness to peers (OR = 2.3; 95% CI, 1.8-3.0) and trying to look like females on television, in movies, or in magazines (OR= 1.9; 95% CI, 1.6-2.3) were predictive of beginning to purge at least monthly. Regardless of the covariates included in the logistic regression model, the risk of beginning to purge increased approximately 30% to 40% per 1-category increase in frequency of trying to look like females on television, in movies, or in magazines. CONCLUSIONS: Both peers and popular culture, independent of each other, exert influence on girls' weight control beliefs and behaviors. Therefore, to make eating disorder prevention programs more effective, efforts should be made to persuade the television, movie, and magazine industries to employ more models and actresses whose weight could be described as healthy, not underweight.

The length of uncomplicated human gestation.

By retrospective exclusion of gestations with known obstetric complications, maternal diseases, or unreliable menstrual histories, we found that uncomplicated, spontaneous-labor pregnancy in private-care white mothers is longer than Naegele's rule predicts. For primiparas, the median duration of gestation from assumed ovulation to delivery was 274 days, significantly longer than the predicted 266 days (P = .0003). For multiparas, the median duration of pregnancy was 269 days, also significantly longer than the prediction (P = .019). Moreover, the median length of pregnancy in primiparas proved to be significantly longer than that for multiparas (P = .0032). Thus, this study suggests that when estimating a due date for private-care white patients, one should count back 3 months from the first day of the last menses, then add 15 days for primiparas or 10 days for multiparas, instead of using the common algorithm for Naegele's rule.

Overweight, weight concerns, and bulimic behaviors among girls and boys.

OBJECTIVE: To assess the prevalence rates and correlates of overweight, concern with weight, and bulimic behaviors. METHOD: A survey was completed by a population-based sample of 16,114 boys and girls aged 9 to 14 years. RESULTS: Although fewer girls (19%) than boys (26%) were overweight, more girls (25% versus 22%) perceived themselves as overweight (p < .001). The proportion of girls reporting trying to lose weight increased with age (p < .001). The prevalence of binge eating at least monthly increased with age among the girls, but remained stable among the boys. The prevalence of purging was low (< or = 1%) and comparable between genders until age 13. Among the 13- and 14-year-olds, girls were significantly more likely than boys to report using laxatives or vomiting to control weight (p < or = .001). Purging was independently positively associated with stage of pubertal development (girls: odds ratio [OR] = 2.1, 95% confidence interval [CI] 1.6-2.7; boys: OR = 1.5, 95% CI 1.0-2.2) and overweight (girls: OR = 1.9, 95% CI 1.2-3.0; boys: OR = 2.7, 95% CI 1.4-5.1). CONCLUSIONS: Misperception of being overweight and concern with weight were common. Purging was a very rare behavior, but increased with pubertal development. Among the girls, the prevalence increased sharply around the onset of adolescence.

Comparing physical activity questionnaires for youth: seasonal vs annual format.

BACKGROUND: In large cohort studies of older children, self-report is the only practical way to assess physical activity. Assessing usual activity over the entire year is desirable, but children and adolescents may overestimate activities with high seasonal variability. Use of questionnaires in which individuals report each activity by season may improve accuracy. METHODS: A total of 6782 girls and 5110 boys, aged 9-14 years in 1996, completed self-administered activity questionnaires in 1996 and in 1997. In 1996, participants reported the average time spent in each of 17 activities during the previous 12 months; in 1997, we also asked for the average time spent in the previous year, but within each of the four seasons. RESULTS: Girls reported a median of 12.8 hours/week total activity in 1996 and 10.4 hours/week in 1997. For boys, the estimates were 15.5 hours/week and 13.4 hours/week, respectively. Girls and boys within 1-year age strata (e.g., comparison of 10-year olds in 1996 with 10-year olds in 1997) reported an average of 3.7 and 3.1 fewer hours per week, respectively, on the 1997 seasonal format versus the 1996 annual format questionnaire. In longitudinal analyses, the difference between the annual and the seasonal estimates was greater if participants did the activity in fewer seasons in 1997. CONCLUSIONS: In comparison to an annual format questionnaire, a seasonal format questionnaire may improve accuracy of self-report of physical activity by reducing over-reporting of activities in which pre-adolescents and adolescents engage in fewer seasons.

Examiner reliability in dental radiography.

In long-term investigations involving a large number of study participants, it is frequently necessary to employ the use of multiple examiners who must exhibit high levels of inter- and intra-examiner reliability in order to minimize examiner bias, which can distort scientific findings. This report on the calibration of four examiners in a large project investigating the efficacy of dental radiography shows high levels of examiner reliability using various statistical measures of agreement. Levels of intra-examiner agreement using Cohen's Kappa index were 0.75 and higher at baseline, and remained at approximately the same level (0.80) throughout the 24-month period of the study. The Kappa index of inter-examiner agreement among the six pairings of the four examiners ranged from 0.68 to 0.80 for caries and 0.72 and 0.83 for periodontal disease. Values of four statistical measures of agreement (proportional agreement, Kendall's rank correlation, Cohen's Kappa index, and Cohen's weighted Kappa index) were determined to show the importance of using measures, such as the Kappa index, which take chance agreement into account.

Multiple-outcomes meta-analysis of treatments for periodontal disease.

The results of periodontal therapy vary by disease severity, outcome measure, and method of data analysis. Several clinical trials and a subsequent meta-analysis have demonstrated that, for teeth with severe disease, surgery decreases probing depth (PD) and increases attachment level (AL) more than non-surgical treatment. For other disease levels, the choice of therapy depends on the outcome measure. When clinical trials use two or more outcome measures (such as PD and AL), investigators ordinarily analyze each outcome separately. When the correlations are incorporated among the outcomes, a meta-analysis can use generalized-least-squares (GLS) regression to analyze multiple outcomes jointly. We applied the GLS multiple-outcomes model in a meta-analysis of 5 trials comparing surgical and non-surgical periodontal treatments, each assessing the outcomes PD and AL one year after treatment. The clinical conclusions are similar to those reported earlier, but our estimates of the relative benefits of surgical and non-surgical treatment should be more accurate, because the GLS method takes into account correlation between AL and PD. When correlations between the two outcomes rise, as they do with increasing severity of disease, the GLS estimates depart from those derived from separate analyses of PD and AL.

Effects of body fat on ventilatory function in children and adolescents: cross-sectional findings from a random population sample of school children.

Childhood obesity is associated with a range of adverse consequences, and the prevalence is increasing in developed nations. Most of the literature on obesity and ventilatory function in children concerns samples selected for gross obesity with relatively little detail available from random population samples. This report examines the effect of total body fat as a percentage of weight (TBF%) on ventilatory function in a nationally representative sample of 2,464 Australian school children aged 9, 12, and 15 years. Forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) were used as measures of ventilatory function. TBF% was estimated from skinfold thickness measurements. Ventilatory function was adjusted (for height and then for both height and weight) using linear regression on a logarithmic scale. Adjustment was performed within separate strata of age and gender. Analysis of covariance was used for hypothesis testing. Height-adjusted FVC and FEV1 values increased significantly with increasing weight within each age and gender group and for all subjects combined (P < 0.0001). The effect of TBF% independent of lean tissue was examined using FVC and FEV1 values adjusted for both height and weight, because body weight measures both lean and fat mass. Adjusted FVC and FEV1 values decreased significantly with increasing TBF% within each age and gender group and for all subjects combined (P < 0.0001). Ventilatory function decreased with increasing proportions of body fat. This is consistent with previous findings on lean tissue mass and ventilatory function. Although the magnitude of the effect was relatively small in clinical terms, from a public health perspective our findings indicate yet another adverse consequence of childhood obesity.

Dietary essential fatty acids, long-chain polyunsaturated fatty acids, and visual resolution acuity in healthy fullterm infants: a systematic review.

BACKGROUND: Biologically active neural tissue is rich in docosahexaenoic acid (DHA), an omega-3 long-chain polyunsaturated fatty acid (LCPUFA). We conducted a systematic review to examine the nature of discordant results from studies designed to test the hypothesis that dietary DHA leads to better performance on visually-based tasks in healthy, fullterm infants. We also conducted a meta-analysis to derive combined estimates of behavioral- and electrophysiologic-based visual resolution acuity differences and sample sizes that would be useful in planning future research. STUDY DESIGN AND METHODS: Twelve empirical studies on LCPUFA intake during infancy and visual resolution acuity were identified through bibliographic searches, examination of monograph and review article reference lists, and written requests to researchers in the field. Works were reviewed for quality and completeness of information. Study design and conduct information was extracted with a standardized protocol. Acuity differences between groups consuming a source of DHA and groups consuming DHA-free diets were calculated as a common outcome from individual studies; this difference score was evaluated against a null value of zero and then used, with the method of DerSimonian and Laird (Meta-analysis in clinical trials. Control Clin Trials 1986;7:177-188), to derive combined estimates of visual resolution acuity differences within seven age categories. RESULTS OF RANDOMIZED COMPARISONS: The combined visual resolution acuity difference measured with behaviorally based methods between DHA-supplemented formula fed groups and DHA-free formula fed groups is 0.32+/-0.09 octaves (combined difference+/-S.E.M., P=0.0003) at 2 months of age. The direction of this value indicates higher acuity in DHA-fed groups. RESULTS OF NON-RANDOMIZED STUDY DESIGNS: The combined visual resolution acuity difference measured with behaviorally based methods between human milk fed groups and DHA-free formula fed groups is 0.49+/-0.09 octaves (P< or =0.000001) at 2 months of age and 0.18+/-0.08 octaves (P=0.04) at 4 months of age. Acuity differences for electrophysiologic-based measures are also greater than zero at 4 months (0.37+/-0.16 octaves, P=0.02). CONCLUSION: Some aspect of dietary n-3 intake is associated with performance on visual resolution acuity tasks at 2, and possibly, 4 months of age in healthy fullterm infants. Whether n-3 intake confers lasting advantage in the development of visually based processes is still in question.

Epidemiologic study of sound surface trends in a 10-year longitudinal study.

Longitudinal data of 589 men aged 30-65 yr, each followed for 10 yr, were analyzed to identify variables which may be associated with healthy tooth surface loss. A longitudinal linear growth curve model was used. As expected, older cohorts tended to have fewer sound surfaces (P < 0.02), but they also tended to have greater rates of sound surface loss (P < 0.01). Age, bone loss, number of teeth at baseline, gingivitis, pocket depth and calculus were individually correlated (P < 0.05) with the rate of sound surface loss. The number of filled or diseased surfaces at baseline was also marginally correlated (P < 0.06) with rate of sound surface loss.

Longitudinal statistical models for loss of sound surfaces.

Longitudinal data of 50-yr-old men, followed for 10 yr, were analyzed to identify variables which may be associated with healthy tooth surface loss. Three types of longitudinal models were used, arriving at similar conclusions. Predictors of sound tooth surface loss with aging included pocket depth, mobility, and recession.

Longitudinal radiographic analysis of carious lesion progression.

Information on the rate at which carious lesions progress through the enamel of human teeth in an adult population was obtained from dental radiographs taken at 3-yr intervals, over a 10-yr period on 602 men. Clinical measures of calculus deposition, plaque accumulation, gingival inflammation, tooth mobility, periodontal pocket depth, and gingival recession were studied to find predictors that might be of value to the clinician for determining how frequently radiographs should be taken. We estimate that 50% of the enamel lesions on mesial and distal surfaces, if left untreated, would not progress into the dentin until 73 months had elapsed after the lesion was initiated. Significant differences in the progression rate were associated with the arch and tooth type. Patient age, number of decayed or filled surfaces, degree of gingival inflammation, amount of recession, and plaque accumulation were positively associated with more rapid caries progression, while greater numbers of teeth present were predictive of slower disease progression.

Statistical methods for comparing dental diagnostic procedures.

In dental diagnosis, there are typically two or more clinical diagnostic procedures which may be used either independently or jointly to reach a conclusion regarding the presence of a particular disease in a patient. To determine which of these diagnostic procedures are more accurate, statistical methods may be applied to research data in which the true health status as well as the diagnosis provided by each clinical procedure are available on each observation. Results arising from this type of analysis can be of great interest to clinicians when the diagnostic procedures themselves are costly, painful, or even potentially harmful to the patient. Considered here is the special situation encountered in dental research in which each patient can have multiple concurrent cases of a certain disease such as caries, for then the statistical evaluation of diagnostic procedures is even further complicated. This report describes several statistical approaches for comparing the efficacy of diagnostic tests and illustrates their application on data from a study of diagnostic radiographs for dental caries.

Selecting the optimal threshold for the radiographic diagnosis of interproximal caries.

The declining prevalence of dental caries and changes in understanding about the progressive nature of this disease have led to recommendations that new diagnostic criteria be adopted. Selecting the optimum diagnostic threshold requires consideration of the probability of disease, distribution of true and false diagnoses at different test thresholds, and estimates of the consequences of treatment based on these diagnoses. Data from the Veterans Administration Dental Longitudinal Study were used to determine the distribution of true and false diagnoses at progressively more stringent diagnostic thresholds. Estimates of the consequences of treatment provided on the basis of true and false diagnoses were obtained from a randomly selected group of clinicians. The data were combined in a decision analysis to determine the "expected value" of operative treatment at each threshold under varying assumptions about the prevalence of disease, rate of disease progression, and value of treatment. No single diagnostic threshold consistently maximized the benefits of treatment. While patients with a high caries prevalence who experience infrequent recalls would benefit from a diagnostic threshold that includes early lesions, patients with a low caries prevalence who follow good recall schedules should benefit from a more conservative diagnostic threshold.