Hepatitis B reactivation in hepatitis B and C coinfected patients treated with antiviral agents: A systematic review and meta-analysis.

There is an increased awareness of hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients coinfected with HBV treated with pan-oral direct-acting antiviral agents (DAAs). We performed a systematic review and meta-analysis to compare the rate of HBV reactivation in CHC patients coinfected with overt HBV (hepatitis B surface antigen [HBsAg] positive) and occult HBV (HBsAg negative with positive HBV DNA) infection separately, treated with interferon (IFN)-based therapy to those with pan-oral DAAs. The primary outcome was HBV reactivation, and the secondary outcomes included hepatitis due to HBV reactivation, sustained virologic response (SVR) for CHC, loss of HBV DNA and HBsAg seroclearance. Although the pooled incidence rate of HBV reactivation, among CHC patients with overt HBV (n = 779), was similar among those treated with IFN-based therapy (14.5%, P < 0.001) and DAAs (12.2%, P = 0.03; P = 0.91 for heterogeneity between subgroups), it was reported to occur much earlier in those treated with DAAs (4-12 weeks during treatment) than in those treated with IFN-based therapies (most at the end of treatment and some during follow-up). Also, studies with DAA-based therapies were more likely to report incidence of hepatitis due to HBV reactivation (12.2% in DAAs vs. 0% in IFN; P = 0.009 for heterogeneity between subgroups). HBV reactivation and hepatitis due to HBV reactivation also occurred, though less frequently in CHC patients with occult HBV infection. CHC SVR was not affected by HBV reactivation (P = 0.27). CONCLUSION: HBV reactivation occurs earlier and is clinically more significant in CHC patients coinfected with overt and occult HBV who are treated with pan-oral DAAs compared with IFN-based therapy. It is therefore important to have all patients screened for evidence of overt or occult HBV infection and managed during pan-oral DAAs therapy. (Hepatology 2017;66:13-26).

Effects of proton-pump inhibitors on functional dyspepsia: a meta-analysis of randomized placebo-controlled trials.

BACKGROUND & AIMS: The aim of this study was to assess systematically the efficacy of proton pump inhibitors (PPIs) in the treatment of functional dyspepsia compared with placebo and to determine if any difference in the response exists between symptom subgroups of functional dyspepsia. METHODS: A literature search was performed through September 2005 in PubMed, Medline, Embase, CINAHL, and Cochrane databases to include randomized, double-blind, placebo-controlled trials evaluating the efficacy of PPIs for the treatment of functional dyspepsia. Relative risk (RR) and relative risk reduction (RRR) and 95% confidence intervals (CI) were calculated under a random-effects model. RESULTS: Seven studies with a total of 3725 patients were identified. PPIs were found to be more effective than placebo for reducing symptoms in patients with functional dyspepsia (RRR, 10.3%; 95% CI, 2.7%-17.3%). The estimated number needed to treat is 14.6 (95% CI, 8.7-57.1). When stratified analyses were performed, a significant difference in the efficacy was observed only in patients with ulcer-like (RRR, 12.8%; 95% CI, 7.2%-18.1%) and reflux-like dyspepsia (RRR, 19.7%; 95% CI, 1.8%-34.3%), but not in those with dysmotility-like (RRR, 5.1%; 95% CI, -10.9% to 18.7%) and unspecified dyspepsia (RRR, -8.0%; 95% CI, -23.7% to 5.6%). The effect of H pylori on the efficacy of PPIs remains unclear. Significant heterogeneity among studies was found for the overall analysis, dysmotility-like dyspepsia, H pylori-negative subgroup, and different dose subgroups. CONCLUSIONS: PPIs are more effective than placebo for the management of patients with ulcer-like and reflux-like functional dyspepsia.

Prolonged seated immobility-associated venous coagulability in a factor V Leiden heterozygote: a case-comparative study.

Prolonged sitting and thrombophilia may compound the risk of venous thromboembolism. In order to investigate suspected local lower limb venous procoagulant changes associated with prolonged sitting-induced venous stasis in a man heterozygous for factor V Leiden (participant X), we qualitatively compared venous coagulability in lower and upper limb plasma in this participant and three other male Caucasians over 8 h of sitting. Of the four participants, participant X had the highest baseline values of prothrombin fragments 1 and 2, thrombin-antithrombin III complexes, tissue plasminogen activator, plasminogen activator inhibitor 1, D-dimer and soluble thrombomodulin. Over time, in participant X, venous prothrombin fragments 1 and 2, thrombin-antithrombin III complexes, and soluble thrombomodulin decreased in both limbs; D-dimer decreased in the lower limbs but increased in the upper limbs; the tissue plasminogen activator/plasminogen activator inhibitor 1 molar ratio increased in both limbs; and minimal changes were noted in haematocrit. A foot volume increase was associated with vague symptoms towards the end of the study. Overall, these changes were similar to those observed in other participants. It is concluded from this case comparison that prolonged sitting of 8 h duration under normal atmospheric conditions did not result in local, as well as systemic, procoagulant haemostatic responses in a heterozygote for factor V Leiden when compared with other healthy volunteers. However, this observed, possibly adaptive, response is more likely to be compromised in factor V Leiden subjects during continued or increased venous endothelial stress or in the presence of other venous thromboembolism risk factors.

The association between seated immobility and local lower-limb venous coagulability in healthy adult volunteers: a simulation of prolonged travel immobility.

This is the first study to examine the hypothesis that prolonged sitting is associated with procoagulant changes in the local lower-limb venous system. A comparison was made with upper-limb venous changes. Changes in markers of thrombin generation, fibrinolysis, endothelial perturbation and haemoconcentration were analysed as 10 healthy adult male participants sat for 8 h. The change in foot volume was estimated. Subjective venous thromboembolism assessment was undertaken hourly, along with 2-week and 4-week safety follow-up for clinical events. Expected increases in median prothrombin fragments 1 and 2, thrombin-antithrombin complex and D-dimer were not observed in either limb. An increase greater than 45% in the median tissue plasminogen activator and plasminogen activator-1 molar ratio (t-PA/PAI-1), and a decrease greater than 15% in median soluble thrombomodulin were noted in both limbs. Median haematocrit decreased minimally (1%) in the lower limbs, while the foot volume increased by 4%. Subjects experienced vague symptoms after 6 h of sitting, but none developed symptomatic venous thromboembolism. Upper and lower-limb changes in biomarkers did not correlate, except those in t-PA/PAI-1 ratio and plasminogen activator-1. Significant correlation was found between changes in the lower-limb t-PA/PAI-1 ratio and right foot volume. This study originally reveals that even in the lower limbs, prolonged daytime cramped sitting is not associated with significant procoagulant changes in healthy adult male volunteers, and confirms a previous observation that local lower-limb venous changes are not identically reflected in the upper limbs.

Is proton pump inhibitor testing an effective approach to diagnose gastroesophageal reflux disease in patients with noncardiac chest pain?: a meta-analysis.

BACKGROUND: Gastroesophageal reflux disease (GERD) is common in patients with noncardiac chest pain (NCCP). Results of studies evaluating the accuracy of a proton pump inhibitor (PPI) treatment as a diagnostic test for GERD-related NCCP have varied. We evaluated the overall accuracy of this modality. METHODS: We searched the PubMed, MEDLINE, EMBASE, CINAHL, and Cochrane databases to May 2004 and included randomized, placebo-controlled studies evaluating the accuracy of findings from PPI testing in the diagnosis of GERD in patients with NCCP. The GERD diagnosis was confirmed by results of endoscopy and/or 24-hour esophageal pH monitoring. A summary diagnostic odds ratio and summary receiver operating characteristic curve analysis were used to estimate the overall accuracy and to explore any contributing factors. RESULTS: Six studies met the inclusion criteria. The overall sensitivity and specificity of a PPI test were 80% (95% confidence interval [CI], 71%-87%) and 74% (95% CI, 64%-83%), respectively, compared with 19% (95% CI, 12%-29%) and 77% (95% CI, 62%-87%), respectively, in the placebo group. The PPI test showed a significant higher discriminative power, with a summary diagnostic odds ratio of 19.35 (95% CI, 8.54-43.84) compared with 0.61 (95% CI, 0.20-1.86) in the placebo group. The impact of the prevalence of GERD and treatment duration on the accuracy of the test could not be determined because of the lack of an adequate number of studies. CONCLUSION: The use of PPI treatment as a diagnostic test for detecting GERD in patients with NCCP has an acceptable sensitivity and specificity and could be used as an initial approach by primary care physicians to detect GERD in selected patients with NCCP.

Do patients with non-ulcer dyspepsia respond differently to Helicobacter pylori eradication treatments from those with peptic ulcer disease? A systematic review.

AIM: It is controversial whether patients with non-ulcer dyspepsia (NUD) respond differently to Helicobacter pylori (H pylori) eradication treatment than those with peptic ulcer disease (PUD). To review the evidence for any difference in H pylori eradication rates between PUD and NUD patients. METHODS: A literature search for full articles and meeting abstracts to July 2004 was conducted. We included studies evaluating the efficacy of a proton pump inhibitor (P) or ranitidine bismuth citrate (RBC) plus two antibiotics of clarithromycin (C), amoxicillin (A), metronidazole (M), or P-based quadruple therapies for eradicating the infection. RESULTS: Twenty-two studies met the criteria. No significant difference in eradication rates was found between PUD and NUD patients when treated with 7-d RBCCA, 10-d PCA or P-based quadruple therapies. When the 7-d PCA was used, the pooled H pylori eradication rate was 82.1% (431/525) and 72.6% (448/617) for PUD and NUD patients, respectively, yielding a RR of 1.15 (95%CI 1.01-1.29). However, the statistically significant difference was seen only in meeting abstracts, but not in full publications. CONCLUSION: There is no convincing evidence to suggest that NUD patients respond to H pylori eradication treatments differently from those with PUD, although a trend exists with the 7-d PCA therapy.

Traveler's thrombosis: a systematic review.

BACKGROUND: Anecdotal evidence suggests a possible link between travel and venous thromboembolism (VTE). We systematically evaluated the evidence from observational studies. METHODS: We searched studies evaluating the risk of venous thrombosis in relation to traveling from MEDLINE and EMBASE up tp March 2004, together with a hand search of reference lists from retrieved literature, and we contacted some of the experts. Observational studies estimating the risks of VTE and isolated calf vein thrombosis were eligible. Methodologic quality was assessed based on prior criteria, and meta-analysis was considered where applicable. RESULTS: A total of 194 English-language publications were initially identified. Sixteen studies were included: 9 case-control, 2 prospective controlled, and 5 other observational studies. They differed drastically in study designs, selection of controls where applicable, mode and duration of travel, and subtypes of VTE under consideration. Ten studies concluded that travel, mostly through air and of prolonged duration, is a risk factor for venous thrombosis and/or pulmonary embolism, and the risk increases for passengers with preexisting venous thrombosis risk factors. Outcomes examined ranged from asymptomatic isolated calf muscle vein thrombosis to severe fatal pulmonary embolism. CONCLUSIONS: Current literature is controversial over any association between travel and VTE, and although the quality and power of these studies have been variable, studies of higher quality have shown a strong and significant association between prolonged air travel and VTE. No conclusions could be drawn about other modes of transportation. Since VTE is a disease of multifactorial causation, those with preexisting VTE risk factors are most vulnerable.

A longitudinal study of pediatric body mass index values predicted health in middle age.

BACKGROUND AND OBJECTIVE: To characterize the use of pediatric body mass index (BMI) to predict obesity, overweight, and diseases in middle age. METHODS: A longitudinal study of people born in a week in 1958 (n=12,327). The main outcome measures are obesity (BMI > or = 30) and overweight (BMI > or = 25) at age 33 and disease history self-reported at age 42. Receiver operating characteristic (ROC) analysis was performed using BMI measured at ages 7, 11, and 16 years as predictors. RESULTS: BMI values measured at age 11 could predict obesity at age 33 with areas under ROC curve (AUC) of 0.78 for males and 0.80 for females (each P < .001). BMI values at age 11 predicted overweight with slightly smaller AUC (each P < .001). They could also predict history of diabetes and hypertension (AUC=0.60 and 0.56, respectively, each P < .01), both sexes pooled. Prediction based on BMI at age 7 was less satisfactory; that at 16 gave limited improvement. Cutoff points based on ROC curves, the international reference, and the 85th and 95th percentiles gave very different profiles of diagnostic features. CONCLUSION: Pediatric BMI may predict adult obesity and overweight with a reasonable profile of sensitivity and specificity.

Early spontaneous catch-up growth.

We explored factors related to early catch-up growth in healthy children in Göteborg, Sweden. Most (82.9%) infants born small for gestational age (SGA) showed catch-up growth during their first 6 months, and 94.3% reached a final height within the normal range. At 6 months, 21 SGA children remained short and 45 non-SGA babies fell below the -2 SDS cutoff in height. Of these 66 short infants, 10 (15.2%) remained short into adulthood and 56 showed spontaneous catch-up growth. Fetal growth should be defined by body size at 6 months of age rather than at birth because most SGA infants catch up before 6 months, and furthermore, fetal growth regulatory mechanisms, such as insulin-like growth factor-I and -II, are the primary growth-promoting factors until 6 months of age.

Assessing heterogeneity in meta-analyses of Helicobacter pylori infection-related clinical studies: a critical appraisal.

OBJECTIVE: To critically assess the meta-analyses of Helicobacter pylori infection-related clinical studies, particularly the handling of between-study heterogeneity. METHODS: A qualitative, all-language, systematic literature search was performed in Medline, PubMed, BioMed Central and Embase up to February 2003, supplemented by a manual search of major relevant journals. Assessment was according to modified criteria for literature searching, eligibility criteria, validity assessment, data extraction and presentation. Five parameters were used to assess the quality of the meta-analyses in handling between-study heterogeneity. RESULTS: Of 84 potentially relevant citations, 47 were systematic reviews and of them 38 were meta-analyses. Of these 38 studies, 15 (39.5%) had conducted a literature search of multiple databases and 34 (89.5%) had conducted a supplementary manual search. The eligibility criteria were clearly presented in 81.6% of studies, but the quality of the primary studies was assessed in only 26.3%. The process and strategy for data extraction was reported in 57.9% of all studies; 19 (50%) studies planned statistical tests of between-study homogeneity and the results were reported in 18, but the level of statistical significance was reported in only 11 (57.9%). The selection of and justification for a statistical model was presented in 39.5% and 26.3% of studies, respectively. Among the 11 meta-analyses in which statistical between-study heterogeneity was reported, 54.5% ignored the statistical findings and proceeded to pool the study results. The implications of between-study heterogeneity were discussed in only 8 studies. CONCLUSIONS: Many methodological flaws were identified in the meta-analyses of H. pylori-related clinical studies, particularly for assessing, reporting and interpreting between-study heterogeneity. This warrants consistent and urgent adherence by reviewers and journal editors to the methodological guidelines for meta-analyses.

Environmental factors on the SARS epidemic: air temperature, passage of time and multiplicative effect of hospital infection.

The study sought to identify factors involved in the emergence, prevention and elimination of severe acute respiratory syndrome (SARS) in Hong Kong during 11 March to 22 May 2003. A structured multiphase regression analysis was used to estimate the potential effects of weather, time and interaction effect of hospital infection. In days with a lower air temperature during the epidemic, the risk of increased daily incidence of SARS was 18.18-fold (95% confidence interval 5.6-58.8) higher than in days with a higher temperature. The total daily new cases might naturally decrease by an average of 2.8 patients for every 10 days during the epidemic. The multiplicative effect of infected hospital staff with patients in an intensive care unit (ICU) and the proportion of SARS patients in ICUs might respectively increase the risk of a larger SARS epidemic in the community. The provision of protective gear in hospitals was also a very important factor for the prevention of SARS infection. SARS transmission appeared to be dependent on seasonal temperature changes and the multiplicative effect of hospital infection. SARS also appeared to retreat naturally over time.

Secular trends in pubertal development.

OBJECTIVE: To describe the secular trend in pubertal development in relation to the secular trend in height. METHODS: Literature review of cross-sectional, longitudinal and twin studies. RESULTS: Globally, there is a secular trend in adolescent growth for an increased mean final height at adulthood. To a lesser extent, there is also a secular trend towards earlier puberty. However, it seems that the two trends are not strongly connected. The increase in average height over the generations can, to a large extent, be explained by an earlier onset of the growth hormone-dependent phase of growth in early life. The age when this growth 'spurt' occurs in childhood strongly correlates with final height, but is not related to the age at peak height velocity during puberty. There is a large variation in the timing of the onset of puberty; it is largely influenced genetically, as implied by studies in twins. The single environmental factor that stands out as most significant - possibly explaining as much as 25% of the variation in the timing of puberty - is simply nutritional status in childhood; overnutrition and obesity seem to trigger pubertal onset. However, recent studies have identified that both shortness and thinness at birth are also associated with earlier pubertal maturation - a reverse of their impact during childhood years. CONCLUSIONS: More longitudinal studies are needed to understand the short- and long-term consequences of secular changes in both final height and pubertal development before we know how important the trends are.

Probability of adult overweight and risk change during the BMI rebound period.

OBJECTIVE: To develop a probability chart of adult overweight based on childhood body mass index (BMI) values and to evaluate the BMI change during the BMI rebound period during childhood, in different populations, with the use of risk function curves. RESEARCH METHODS AND PROCEDURES: A longitudinal growth study of 3650 full-term healthy Swedish children followed from birth to 18 years of age. Weight and height values of our subjects were obtained. RESULTS: A probability chart for reaching a BMI > 23 kg/m(2) at 18 years of age was constructed for boys and girls. For example, a BMI of 18 kg/m(2) at 4 years of age is associated with 0.70 probability of attaining a BMI > 23 kg/m(2) at 18 years of age in boys; a BMI of 16 kg/m(2) at 4 years of age leads to 0.40 probability of having a BMI > 23 kg/m(2) at 18 years of age in girls. Children with an obvious BMI rebound before 8 years of age have a high risk of being overweight at 18 years of age. There is a clear trend of BMI increase from the 1970s to the 1990s in U.S. children from a parallel dataset, and Hispanic children are at the highest risk of adult overweight. DISCUSSION: The probability chart for adult overweight developed here provides a functional method of defining childhood obesity that is based on the risk of long-term ill health rather than on a certain statistical cut-off point. It will help pediatricians or healthcare workers identify those children who are at a high risk of becoming overweight in adulthood, which will allow clinical intervention at younger ages.

Longitudinal growth during infancy and childhood in children from shanghai: predictors and consequences of the age at onset of the childhood phase of growth.

The age at onset of the childhood phase of growth, normally occurring between 6 and 12 mo, is recognized to be an important time during postnatal human development. The aims of this present work were to identify predictors for the age at onset of the childhood phase of growth. Furthermore, this work aimed to examine the consequences that this timing would have on the subsequent heights of 1720 Shanghai children. The mean age of the infants at onset of the childhood phase of growth was 11.2 mo in boys and 10.7 mo in girls. Compared with their Swedish counterparts, these means occurred 1.3 mo later in boys and 1.4 mo later in girls. Both age at onset of the childhood phase of growth and length at 6 mo of age significantly (p < 0.05) contributed to the attained height from 12 mo of age onward; 1-mo delay in the onset of the childhood phase of growth reduced height at 5 y of age by 0.4 cm in boys and 0.5 cm in girls. The age at onset of the childhood phase of growth was negatively associated (p < 0.001) with mid-parental height, although positively related (p < 0.001) to height at 6 mo of age. There was a distinct body mass index pattern of Chinese children between birth and 6 y of age in comparison with white values. There was a sharp increase in body mass index in Shanghainese during their first 6 mo of life, followed by a gradual decline up to 24 mo. In conclusion, the age at childhood onset is equally important when studying children from Shanghai as it is with their Swedish counterparts.

Pubertal growth assessment.

Almost all available sets of height growth reference values are constructed in a cross-sectional manner, except for a few studies in which longitudinal sampling was used. Such reference values are, however, flawed because of considerable individual variation in the timing of puberty, especially among children with early or late pubertal maturation. An additional complicating factor is that the magnitude of the total pubertal growth spurt is significantly larger among those individuals with early pubertal maturation, compared with late maturation. Based on the growth records of 145 healthy Swedish children followed longitudinally, this study introduces a pre-pubertal standard for the assessment of pre-pubertal height for children with late onset of puberty. By plotting the height values of a child in a chart containing pre-pubertal reference values, the onset of the pubertal growth spurt can be identified by a change in the pre-pubertal height standard deviation score values of 0.3 standard deviations or more over a period of 1 year. Once the pubertal onset is established, a highly accurate final height prediction method can be applied to the data, as described in this article, in which height and age at pubertal onset are the only two measures required. The r(2) value of the prediction model was over 0.80 for both sexes. Finally, a method for assessing total pubertal height gain is presented. The method adjusts for the timing of puberty and is based on the height and age at pubertal onset, plus the observed final height.

Growth in early life and its relation to pubertal growth.

BACKGROUND: The timing and magnitude of pubertal growth in relation to fetal, infancy and childhood growth have not been explored. METHODS: We used data from a longitudinal growth study of 3650 full-term healthy children who were born in Gothenburg, Sweden in 1973-1975. This analysis included 2738 children with height and weight measurements available both in early life and during adolescence. RESULTS: We found that faster linear growth during infancy and childhood was associated with earlier peak height velocity during adolescence. In contrast, greater height and body mass index (BMI) at birth were associated with later peak height velocity in adolescence. Children with faster linear growth and greater BMI in infancy and childhood had less height gain between ages 8 and 18. However, greater height and BMI at birth were associated with more height gain between ages 8 and 18 after adjusting for height and BMI in childhood. CONCLUSIONS: Both length and BMI (at birth, in infancy and during childhood) are associated with the timing and magnitude of pubertal growth. Being small at birth is associated with early puberty and a reduced height gain during adolescence.

Non-steroidal anti-inflammatory drug use and the risk of gastric cancer: a systematic review and meta-analysis.

BACKGROUND: The relationship between the use of non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin, and the risk of gastric cancer has not been well studied. We performed a systematic review and meta-analysis of published studies to evaluate the association between use of this class of drugs and the risk of gastric cancer. METHODS: A fully recursive literature search to January 2003 was conducted in MEDLINE, PubMed, and CANCERLIT to identify potentially relevant case-control or cohort studies. Summary odds ratios (ORs) and 95% confidence intervals (CIs) were calculated under a random-effects model. RESULTS: Nine studies (eight case-control and one cohort) with a total of 2831 gastric cancer case patients were identified. NSAID use was associated with a reduced risk of gastric cancer, with a summary odds ratio of 0.78 (95% CI = 0.69 to 0.87). Users of aspirin (OR = 0.73, 95% CI = 0.63 to 0.86) and non-aspirin NSAIDs (OR = 0.74, 95% CI = 0.55 to 1.00) experienced similar magnitudes of risk reduction. Regular users of NSAIDs (OR = 0.57, 95% CI = 0.44 to 0.74) experienced a lower risk of gastric cancer relative to nonusers than did irregular users (OR = 0.76, 95% CI = 0.62 to 0.94; P =.09 versus regular users). A stratified analysis showed that NSAID use was associated with a statistically significant reduction in risk of noncardia gastric cancer (OR = 0.72, 95% CI = 0.58 to 0.89), but not of gastric cancer at the cardia (OR = 0.80, 95% CI = 0.53 to 1.20). There was no evidence that study design or type of control subject substantially influenced the estimate of effects. CONCLUSION: NSAID use was associated with a decreased risk of gastric cancer in a dose-dependent manner. This finding warrants proper clinical trials in populations with high risk of gastric cancer.