Management of Helicobacter pylori infection in Latin America: A Delphi technique-based consensus

AIM: To optimize diagnosis and treatment guidelines for this geographic region, a panel of gastroenterologists, epidemiologists, and basic scientists carried out a structured evaluation of available literature.METHODS: Relevant questions were distributed among the experts, who generated draft statements for consideration by the entire panel. A modified three-round Delphi technique method was used to reach consensus. Critical input was also obtained from representatives of the concerned medical community. The quality of the evidence and level of recommendation supporting each statement was graded according to United States Preventive Services Task Force criteria.RESULTS: A group of ten experts was established. The survey included 15 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 50% in the first round, 73.3% in the second round and 100% in the third round. Main consensus recommendations included: (1) when available, urea breath and stool antigen test (HpSA) should be used for non-invasive diagnosis; (2) detect and eradicate Helicobacter pylori (H. pylori) in all gastroscopy patients to decrease risk of peptic ulcer disease, prevent o retard progression in patients with preneoplastic lesions, and to prevent recurrence in patients treated for gastric cancer; (3) further investigate implementation issues and health outcomes of H. pylori eradication for primary prevention of gastric cancer in high-risk populations; (4) prescribe standard 14-d triple therapy or sequential therapy for first-line treatment; (5) routinely assess eradication success post-treatment in clinical settings; and (6) select second- and third-line therapies according to antibiotic susceptibility testing.CONCLUSION: These achievable steps toward better region-specific management can be expected to improve clinical health outcomes.     

Reproductive factors, oral contraceptive use, and human papillomavirus infection: pooled analysis of the IARC HPV prevalence surveys.

High parity, early age at first full-term pregnancy (FTP), and long-term oral contraceptive (OC) use increase cervical cancer risk, but it is unclear whether these variables are also associated with increased risk of acquisition and persistence of human papillomavirus (HPV) infection, the main cause of cervical cancer. Information on reproductive and menstrual characteristics and OC use were collected from 14 areas worldwide, among population-based, age-stratified random samples of women aged 15 years or older. HPV testing was done using PCR-based enzyme immunoassay. Unconditional logistic regression was used to estimate the odds ratios (OR) of being HPV-positive according to reproductive and menstrual factors and corresponding 95% confidence intervals (CI). When more than two groups were compared, floating CIs (FCI) were estimated. A total of 15,145 women (mean age, 40.9 years) were analyzed. Women with >or=5 FTPs (OR, 0.90; 95% FCI, 0.76-1.06) showed a similar risk of being HPV-positive compared with women with only one FTP (OR, 1.00; 95% FCI, 0.86-1.16). However, nulliparous women showed an OR of 1.40 (95% CI, 1.16-1.69) compared with parous women. Early age at first FTP was not significantly related to HPV positivity. HPV positivity was similar for women who reported >or=10 years of use of OCs (OR, 1.16; 95% FCI, 0.85-1.58) and never users of OCs (OR, 1.00; 95% FCI, 0.90-1.12). Our study suggests, therefore, that high parity, early age at first FTP, and long-term OC use are not associated with HPV prevalence, but rather these factors might be involved in the transition from HPV infection to neoplastic cervical lesions.     

Profile of urinary arsenic metabolites during pregnancy

Chronic exposure to inorganic arsenic (In-As) from drinking water is associated with different health effects, including skin, lung, bladder, and kidney cancer as well as vascular and possibly reproductive effects. In-As is metabolized through the process of methylation, resulting in the production and excretion of methylated species, mainly monomethylarsenate (MMA) and dimethylarsenate (DMA). Because a large percentage of the dose is excreted in urine, the distribution of urinary In-As, MMA, and DMA is considered a useful indicator of methylation patterns in human populations. Several factors affect these patterns, including sex and exposure level. In this study, we investigated the profile of urinary In-As, MMA, and DMA of pregnant women. Periodic urine samples were collected from early to late pregnancy among 29 pregnant women living in Antofagasta, Chile, who drank tap water containing 40 micro g/L In-As. The total urinary arsenic across four sampling periods increased with increasing weeks of gestation, from an initial mean value of 36.1 to a final value of 54.3 micro g/L. This increase was mainly due to an increase in DMA, resulting in lower percentages of In-As and MMA and a higher percentage of DMA. Our findings indicate that among women exposed to moderate arsenic from drinking water during pregnancy, changes occur in the pattern of urinary arsenic excretion and metabolite distribution. The toxicologic significance of this is not clear, given recent evidence suggesting that intermediate methylated species may be highly toxic. Nevertheless, this study suggests that arsenic metabolism changes throughout the course of pregnancy, which in turn may have toxicologic effects on the developing fetus. Key words: arsenic, arsenic metabolism, arsenic methylation, Chile, pregnancy, urinary arsenic.     

Impact of infertility and infertility treatments on quality of life and levels of anxiety and depression in women undergoing in vitro fertilization

Abstract

This study aims to evaluate levels of anxiety and depression in women, correlated with infertility per se and with infertility treatments, highlighting predictors of higher levels of distress. Two validated standardized questionnaires, the Hospital Anxiety and Depression Scale (HADS) and the Fertility Quality of Life (FertiQoL), were administered to 89 women both before their first cycle of infertility treatment and again at the end of the ovarian stimulation for in vitro fertilization (IVF). Women's levels of anxiety were significantly higher before the treatment than during the treatment itself. Stratifying the women in three groups based on principal cause of infertility (male infertility, female infertility, or both male and female), we found significantly higher levels of anxiety and general distress in patients under treatment for female infertility. Higher anxiety levels in our sample before the treatment are probably an effect of not knowing what they are expected to do to solve their problem. Moreover, when the cause of infertility is exclusively female, women experience higher levels of anxiety and general distress both before and during the treatment, probably correlated to a sense of guilt. These data help the treating physician to better counsel patients and to provide a more focused psychological support.     

Impact of Haemophilus influenzae type b polysaccharide-tetanus protein conjugate vaccine on responses to concurrently administered diphtheria-tetanus-pertussis vaccine.

OBJECTIVE--To assess whether serum antibody responses to diphtheria-tetanus-pertussis (DTP) vaccine were affected by coadministration of Haemophilus influenzae type b capsular polyribosylribitol phosphate polysaccharide-tetanus protein (PRP-T) conjugate vaccine when given to patients at 2, 4, and 6 months of age. DESIGN--Randomized, double-blind clinical trial. SETTING--Urban Santiago, Chile. PATIENTS--Healthy infants assembled from health centers. Two hundred seventy-eight (74%) of 375 eligible infants participated; 222, who complied with the complete protocol, constituted the primary group under analysis. INTERVENTIONS--One of three vaccine regimens was given to study participants at 2, 4, and 6 months of age, either DTP mixed in the same syringe as PRP-T (group 1); DTP and PRP-T given at separate injection sites (group 2); or DTP without PRP-T (group 3). PRIMARY OUTCOME MEASURES--Titers of serum antidiphtheria toxoid, antitetanus toxoid, and pertussis agglutinin antibodies were measured in blood samples taken from patients 2 months after each dose. RESULTS--Serum antidiphtheria toxoid and antitetanus toxoid responses showed no important depressions in the patients receiving PRP-T. In contrast, geometric mean titers (GMTs) of pertussis agglutinins, expressed as reciprocal serum dilutions, after both the second and third doses (GMT2, GMT3) were lowest in group 1 (GMT2 = 89; GMT3 = 1230), intermediate in group 2 (GMT2 = 123; GMT3 = 1995), and highest in group 3 (GMT2 = 210; GMT3 = 3090; P less than .05 for trend group 1 less than group 2 less than group 3 after each dose). Antipertussis toxin and antipertussis filamentous hemagglutinin antibody titers also were depressed in patients who received PRP-T. Follow-up of a subset at 18 months revealed an expected decline of pertussis agglutinin titers to near baseline levels in each group. CONCLUSIONS--Concurrent administration of PRP-T vaccine with DTP vaccine, either in the same syringe or at different sites, interfered with antipertussis responses to a primary series of immunizations. Although the clinical significance of this antagonism is uncertain, these data underscore the caution required in decisions to add new vaccines to existing immunization regimens.     

Epidemiology of Helicobacter pylori infection in six Latin American countries (SWOG Trial S0701)

Objective

To investigate the potential determinants of Helicobacter pylori infection between adults 21–65 years old.

Methods

Data are from the initial screening visit of a randomized clinical trial of three antibiotic regimens to eradicate H. pylori, conducted in seven sites (Santiago–Chile, Túquerres–Colombia, Guanacaste–Costa Rica, Copán–Honduras, Obregón and Tapachula–México, León–Nicaragua). Thousand eight hundred and fifty-nine adults from the general population were screened for H. pylori infection using an urea breath test (UBT) and were interviewed to assess socioeconomic-, demographic-, and symptom-related characteristics. Logistic regression was used to assess the relationship between these characteristics and H. pylori positivity at enrollment.

Results

Among the 1,852 eligible participants for whom a conclusive UBT result was obtained, H. pylori prevalence was 79.4 %, ranging from 70.1 to 84.7 % among the seven centers. Prevalence did not differ by sex (female: 78.4, male: 80.9; p = 0.20) or age (p = 0.08). H. pylori positivity increased with increasing number of siblings (p trend <0.0001). Participants with education beyond 12 years were less likely to be UBT-positive (OR 0.4: 0.3–0.6, compared to participants with 0–6 years of schooling) as were those employed outside the home (OR 0.7: 0.6–1.0). Odds of H. pylori infection increased with the presence of certain living conditions during childhood including having lived in a household with an earth floor (OR 1.8: 1.4–2.4), lack of indoor plumbing (OR 1.3: 1.0–1.8) and crowding (OR 1.4: 1.0–1.8, for having more than two persons per bedroom). Regarding current household conditions, living with more than 3 children in the household (OR 1.7: 1.2–2.5) and crowding (OR 1.8: 1.3–2.3) were associated with H. pylori infection.

Conclusions

The prevalence of H. pylori in adults was high and differed significantly among the six Latin American countries studied (p < 0.001). Our findings confirm the strong link between poor socioeconomic conditions and H. pylori infection.     

Geographic variation of gallbladder cancer mortality and risk factors in Chile: a population-based ecologic study

Chile's gallbladder cancer rates are among the highest in the world, being the leading cause of cancer deaths among Chilean women. To provide insights into the etiology of gallbladder cancer, we conducted an ecologic study examining the geographical variation of gallbladder cancer and several putative risk factors. The relative risk of dying from gallbladder cancer between 1985 and 2003 was estimated for each of the 333 Chilean counties, using a hierarchical Poisson regression model, adjusting for age, sex and geographical location. The risk of gallbladder cancer mortality was analyzed in relation to region, poverty, Amerindian (Mapuche) population, typhoid fever and access to cholecystectomy, using logistic regression analysis. There were 27,183 gallbladder cancer deaths, with age and sex-adjusted county mortality rates ranging from 8.2 to 12.4 per 100,000 inhabitants. Rates were highest in inland and southern regions. Compared to the northern-coast, the northern-inland region had a 10-fold risk (95% of confidence interval (95% CI): 2.4-42.2) and the southern-inland region had a 26-fold risk (95% CI: 6.0-114.2). Independent of region, other risk factors for gallbladder cancer included a high Mapuche population (Odds ratio (OR):3.9, 95% CI 1.8-8.7), high typhoid fever incidence (OR:2.9, 95% CI 1.2-6.9), high poverty (OR:5.1, 95% CI 1.6-15.9), low access to cholecystectomy (OR:3.9, 95% CI 1.5-10.1), low access to hospital care (OR:14.2, 95% CI 4.2-48.7) and high urbanization (OR:8.0, 95% CI 3.4-18.7). Our results suggest that gallbladder cancer in Chile may be related to both genetic factors and poor living conditions. Future analytic studies are needed to further clarify the role of these factors in gallbladder cancer etiology.     

3-Dialkylamino-substituted 2H-1,4-benzoxazines

N,N,N',N'-Tetrasubstituted 2-(2-aminophenoxy)malonamides (IX) in the presence of phosphorus oxychloride led to the formation of N,N-dialkyl-3-(dialkylamino)-2H-1,4-benzoxazine-2-carboxamides (XII). In the same way 2-(2-amino-3-pyridyloxy)-N,N,N',N'-tetraethylmalonamide (X) yielded 3-(diethylamino)-N,N-diethyl-2H-pyrido[3,2-b] [1,4]oxazine-2-carboxamide (XIII). Also N,N-dialkyl-2-(2-aminophenoxy)acetamides (XIV) by the action of phosphorus oxychloride afforded 3-(dialkylamino)-2H-1,4-benzoxazines (XV). Some compounds when submitted to pharmacological screening showed a weak depressant activity in the Irwin test.     

Screening trial of human papillomavirus for early detection of cervical cancer in Santiago,Chile

Cervical cancer mortality in Chile is four times higher than in developed countries. We compared the accuracy of human papillomavirus (HPV) DNA testing and conventional Papanicolaou (Pap) testing to detect prevalent precancerous and cancerous lesions in the routine clinical practice of the public health system. Women aged 25 years and older residing in the area covered by three primary care centers of Santiago, Chile, were invited to participate. Eligible women received both HPV DNA (Hybrid Capture 2) and Pap testing. Women positive by either test (Pap: ASCUS+, HC2: RLU/CO ≥1.0) underwent colposcopy and biopsy, as did a sample of double‐negative women with an abnormal cervix at visual inspection or with risk factors for cervical lesions. Crude and verification bias‐corrected sensitivities and specificities were estimated. In total, 8,265 women (98.8% of eligible) had complete screening results. Of these, 10.7% were HPV positive, 1.7% were Pap positive and 1.1% were positive by both tests. In all, 931 (11.3%) women were screen‐positive, of whom 94.3% attended colposcopy. Additionally, 295 control women were invited for colposcopy, of whom 78% attended. In all, 42 CIN2, 45 CIN3 and 9 cancers were identified. Verification bias‐corrected sensitivity for CIN2+ (95% confidence interval) was 92.7% (84.4–96.8) for HPV and 22.1% (16.4–29.2) for Pap; corresponding specificities were 92.0% (91.4–92.6) and 98.9% (98.7–99.0). In conclusion, in routine clinical practice in a developing country, HPV testing was four times more sensitive for CIN2+ than Pap testing, identifying three times more CIN2+ lesions; HPV testing was easily implemented in our established cervical cancer prevention program.     

Molecular techniques in the study of Salmonella typhi in epidemiologic studies in endemic areas: comparison with Vi phage typing

We examined 141 Salmonella typhi strains of known phage type isolated during ongoing epidemiologic studies in Santiago, Chile, and Lima, Peru. Plasmids were present in 12 (17%) of 70 S. typhi isolates from Santiago and 5 (7%) of 71 isolates from Lima; these plasmids were not associated with antimicrobial resistance. Identical 21 kilobase (kb) plasmids (as defined by restriction endonuclease digest pattern) were present in 13 of the 17 plasmid-containing isolates. Virtually identical digest patterns were identified when chromosomal DNA of selected strains from Santiago, Lima, and the United States was extracted and then digested with restriction endonucleases. The similarities among plasmids and chromosomal digest patterns emphasize the homogeneity and possible clonal origin of S. typhi isolates; these data also suggest that there is only a limited role for plasmid and chromosomal analysis as a substitute for phage typing in epidemiologic studies.