Cost-effectiveness of six strategies for Helicobacter pylori diagnosis and management in uninvestigated dyspepsia assuming a high resource intensity practice pattern

<p>Abstract</p> <p>Background</p> <p>Initial assessment of dyspepsia often includes noninvasive testing for <it>Helicobacter pylori </it>infection. Commercially available tests vary widely in cost and accuracy. Although there is extensive literature on the cost-effectiveness of <it>H. pylori </it>treatment, there is little information comparing the cost-effectiveness of various currently used, noninvasive testing strategies.</p> <p>Methods</p> <p>A Markov simulation was used to calculate cost per symptom-free year and cost per correct diagnosis. Uncertainty in outcomes was estimated using probabilistic sensitivity analysis.</p> <p>Results</p> <p>Under the baseline assumptions, cost per symptom-free year was $122 for empiric proton pump inhibitor (PPI) trial, and costs for the noninvasive test strategies ranged from$123 (stool antigen) to $129 (IgG/IgA combined serology). Confidence intervals had significant overlap.</p> <p>Conclusions</p> <p>Under our assumptions for how testing for <it>H. pylori </it>infection is employed in United States medical practice, the available noninvasive tests all have similar cost-effectiveness between one another as well as with empiric PPI trial.</p

Alternative eradication regimens for Helicobacter pylori infection in Indonesian regions with high metronidazole and levofloxacin resistance

Muhammad Miftahussurur,1,2 Langgeng Agung Waskito,2,3 Ari Fahrial Syam,4 Iswan Abbas Nusi,1 Gontar Siregar,5 Marselino Richardo,6 Achmad Fuad Bakry,7 Yudith Annisa Ayu Rezkitha,2,8 I Dewa Nyoman Wibawa,9 Yoshio Yamaoka3,10,11 1Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya 60131, Indonesia; 2Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia; 3Department of Environmental and Preventive Medicine, Faculty of Medicine, Oita University, Yufu 879-5593, Japan; 4Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta 10430, Indonesia; 5Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatera Utara, Medan 20136, Indonesia; 6Department of Internal Medicine, Merauke City General Hospital, Merauke 99656, Indonesia; 7Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, Sriwijaya University, Palembang 30126, Indonesia; 8Department of Internal Medicine, Muhammadiyah University of Surabaya, Surabaya 60113, Indonesia; 9Division of Gastroentero-hepatology, Department of Internal Medicine, Faculty of Medicine, University of Udayana, Denpasar 80232, Indonesia; 10Department of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TX 77030, USA; 11Global Oita Medical Advanced Research Center for Health, Yufu 879-5593, Japan Background: The prevalence of Helicobacter pylori resistance to metronidazole and clarithromycin is high in Indonesia. Moreover, the increasing levofloxacin resistance rates in the absence of bismuth treatment in Indonesia has led to the use of other antibiotics as alternative regimens. Methods: We determined the minimum inhibitory concentrations (MICs) of five alternative antibiotics for H. pylori (rifaximin, rifabutin, furazolidone, garenoxacin, and sitafloxacin) using the agar dilution method and assessed mutations associated with antibiotic resistance using next-generation sequencing. Result: Analysis of 106 strains isolated from 1039 adult dyspeptic patients revealed that none of the strains were furazolidone-resistant. All strains were also sensitive to rifabutin and sitafloxacin. In contrast, the rates of resistance to rifaximin and garenoxacin were high (38.9% and 6.7%, respectively). The strains isolated from patients on Java Island had the highest resistance rates to garenoxacin and rifaximin. In addition, the resistance was distributed evenly among the ethnic groups, ranging between 25.0% and 69.2%. Except for rifaximin, for which the resistance rate was 38.9%, the other four antibiotics could be successfully employed to eradicate levofloxacin- and metronidazole-resistant H. pylori infections in vitro. Interestingly, garenoxacin-sensitive strains were found in regions with high clarithromycin resistance rates such as Bali and Papua Islands. In contrast, rifaximin might not be considered as an alternative antibiotic in regions with high clarithromycin resistance. There was an inconsistent association between gyrA and gyrB mutations and garenoxacin resistance. We confirmed that the I837V (replacement of isoleucine at position 837 with valine), A2414T/V, Q2079K and K2068R were the predominant rpoB point mutations. There was an association between vacA genotypes of H. pylori and rifaximin resistance (P = 0.048). Conclusion: furazolidone-, rifabutin-, and sitafloxacin-based therapies might be considered as alternative regimens to eradicate H. pylori in Indonesia, including regions with high metronidazole and clarithromycin resistance rates. Moreover, sitafloxacin but not garenoxacin should be considered for eradication of levofloxacin-resistant strains. Keywords: Indonesia; drug resistance; Helicobacter pylori; antibiotic

Changing trends in gastrointestinal malignancy in Indonesia: The Jakarta experience

Aims: To identify changing trends in gastrointestinal cancer incidence in Indonesia according to age, gender, histopathology, and cancer location. Methods: We examined retrospectively the demography, cancer location, and pathological characteristics of 295 consecutive gastrointestinal cancer patients admitted to Cipto Mangunkusumo National General Hospital in 2002–2006. We compared these data with data from 343 gastrointestinal cancer patients admitted in 2007–2011. The data were analyzed by chi-square, analysis of variance, Kolmogorov–Smirnov, and Mann–Whitney U tests using SPSS 21.0. Results: The most prevalent gastrointestinal cancers in 2002–2006 and 2007–2011 were colorectal cancer (76.3% and 71.4%), followed by gastric cancer (15.6% and 14.9%), esophageal cancer (7.4% and 7.6%), and duodenal cancer (0.7% and 6.1%).There was an increase in esophageal adenocarcinoma prevalence from 36.4% to 69.2% (p = 0.023). The mean age at diagnosis of esophageal cancer decreased from 53.02 ± 13.12) to 50.43 ± 11.93) years (p = 0.031). The percentage of patients with gastric cancer aged 30–60 years increased from 60.9% to 82.4% (p = 0.018) and the percentage of patients aged > 60 years decreased from 34.8% to 13.7% (p = 0.015). In the histopathological analysis of gastric cancer, the prevalence of adenocarcinoma increased from 58.7% to 78.4% (p = 0.036), whereas the prevalence of signet ring cell carcinoma decreased from 21.7% to 5.9% (p = 0.022). The prevalence of gastric cancer lesions extending to >1 location increased from 2.2% to 27.5% (p = 0.001).The frequency of duodenal cancer among women increased non significantly from 0% to 52.4% (p = 0.261). The demography, histopathology, and location of colorectal cancers did not change between the two periods. Conclusions: Our study shows some changing trends in gastrointestinal malignancy in Indonesia in terms of demography, histopathology, and the location of cancers from 2002–2006 to 2007–2011

Integration of symptomatic, demographical and diet-related comorbidities data with SARS-CoV-2 antibody rapid diagnostic tests during epidemiological surveillance: a cross-sectional study in Jakarta, Indonesia

Objectives Affordable options for COVID-19 epidemiological surveillance are needed. Virus detection by reverse transcription-PCR (RT-PCR) is sensitive but costly, and antigen-based rapid diagnostic tests (RDTs) are cheap but with reduced sensitivity; both detect current infection but not exposure. RDT-IgM/IgG antibodies to SARS-CoV-2 detect exposure but have poor sensitivity for current infection. We investigated if the integration of symptomatic, demographical and diet-related comorbidities data with antibody RDTs improves their potential to assess infection rates in addition to exposure, thereby broadening their utility for surveillance. Design We conducted a cross-sectional study using data from community surveillance for SARS-CoV-2. Health workers collected nasopharyngeal swabs for RT-PCR and RDT antigen assessments and venous blood for RDT-IgM/IgG from symptomatic and asymptomatic persons. Data on age, gender, contact history, symptoms (ie, fever, cough, runny nose, sore throat, headache, dyspnoea and diarrhoea), diet-related comorbidities (ie, diabetes and hypertension) and chest radiology were collected. Setting High-risk communities in Jakarta, Indonesia, in May 2020. Participants 343 community members’ data were included. Outcome measures RDT-IgM/IgG sensitivity, specificity and predictive values and area under receiver operating characteristic curve for RT-PCR positivity using RDT results alone and in combination with other predictors, including symptom components derived from principal component analysis. Results There were 24 PCR-confirmed infections. RDT-IgM/IgG-positive tests were associated with infection (OR 10.8, 95% CI 4.43 to 26.4, p<0.001) with an area under the curve (AUC) of 0.708% and 50% sensitivity, 91.5% specificity, 30.8% positive predictive value (PPV) and 96.1% negative predictive value (NPV). RDT results combined with age, gender, contact history, symptoms and comorbidities increased the AUC to 0.787 and yielded 62.5% sensitivity, 87.0% specificity, 26.6% PPV and 96.9% NPV. Conclusions SARS-CoV-2 RDT-IgM/IgG results integrated with other predictors may be an affordable tool for epidemiological surveillance for population-based COVID-19 exposure and current infection, especially in groups with outbreaks or high transmission

Diagnostic Value of 14C Urea Breath Test for Helicobacter pylori Detection Compared by Histopathology in Indonesian Dyspeptic Patients

Muhammad Miftahussurur,1,2 Adinta Windia,1 Ari Fahrial Syam,3 Iswan Abbas Nusi,1 Ricky Indra Alfaray,2,4 Kartika Afrida Fauzia,2,4 Hartono Kahar,5 Herry Purbayu,1 Titong Sugihartono,1 Poernomo Boedi Setiawan,1 Ummi Maimunah,1 Ulfa Kholili,1 Husin Thamrin,1 Amie Vidyani,1 Dalla Doohan,2 Langgeng Agung Waskito,2 Yudith Annisa Ayu Rezkitha,2,6 Gontar Alamsyah Siregar,7 Yoshio Yamaoka1,4 1Gastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 2Institute of Tropical Disease, Universitas Airlangga, Surabaya, East Java, 60115, Indonesia; 3Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, University of Indonesia, Jakarta, 10430, Indonesia; 4Department of Environmental and Preventive Medicine, Oita University Faculty of Medicine, Yufu, 879-5593, Japan; 5Department of Clinical Pathology, Faculty of Medicine, Universitas Airlangga, Surabaya, East Java, 60286, Indonesia; 6Faculty of Medicine, University of Muhammadiyah Surabaya, Surabaya, East Java, 60113, Indonesia; 7Division of Gastroentero-Hepatology, Department of Internal Medicine, Faculty of Medicine, University of Sumatra Utara, Medan, 20155, IndonesiaCorrespondence: Muhammad MiftahussururGastroentero-Hepatology Division, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Jalan Mayjend Prof. Dr. Moestopo No. 6&ndash; 8, Surabaya, 60286, IndonesiaTel/Fax +6231-502-3865Email [email protected]: Histopathology method is often used as a gold standard diagnostic for Helicobacter pylori infection in Indonesia. However, it requires an endoscopic procedure which is limited in Indonesia. A non-invasive method, such as 14C Urea Breath Test (UBT), is more favorable; however, this particular method has not been validated yet.Patients and Methods: A total of 55 dyspeptic patients underwent gastroscopy and 14C-UBT test. We used Heliprobe&reg; UBT for UBT test. As for the histology, May-Giemsa staining of two gastric biopsies (from the antrum and corpus) were evaluated following the Updated Sydney System.Results: The Receiver Operating Characteristics analysis showed that the optimum cut-off value was 57 with excellence Area under Curve = 0.955 (95% CI = 0.861&ndash; 1.000). By applying the optimum cut-off value, Heliprobe&reg; UBT showed 92.31% for sensitivity, 97.62% for specificity, 92.31% for positive predictive value, 97.62% for negative predictive value, 38.77 for positive likelihood ratio, 0.0788 for negative likelihood ratio, and 96.36% for the accuracy.Conclusion: The 14C-UBT is an accurate test for H. pylori diagnosis with excellent sensitivity, specificity, and accuracy. The different optimum cut-off points suggested that a validation is absolutely necessary for new test prior application to the new population.Keywords: Helicobacter pylori, UBT, diagnostic, infectious diseas

Pandemic inequity in a megacity: a multilevel analysis of individual, community and healthcare vulnerability risks for COVID-19 mortality in Jakarta, Indonesia

Introduction Worldwide, the 33 recognised megacities comprise approximately 7% of the global population, yet account for 20% COVID-19 deaths. The specific inequities and other factors within megacities that affect vulnerability to COVID-19 mortality remain poorly defined. We assessed individual, community-level and healthcare factors associated with COVID-19-related mortality in a megacity of Jakarta, Indonesia, during two epidemic waves spanning 2 March 2020 to 31 August 2021. Methods This retrospective cohort included residents of Jakarta, Indonesia, with PCR-confirmed COVID-19. We extracted demographic, clinical, outcome (recovered or died), vaccine coverage data and disease prevalence from Jakarta Health Office surveillance records, and collected subdistrict level sociodemographics data from various official sources. We used multilevel logistic regression to examine individual, community and subdistrict-level healthcare factors and their associations with COVID-19 mortality. Results Of 705 503 cases with a definitive outcome by 31 August 2021, 694 706 (98.5%) recovered and 10 797 (1.5%) died. The median age was 36 years (IQR 24–50), 13.2% (93 459) were <18 years and 51.6% were female. The subdistrict level accounted for 1.5% of variance in mortality (p<0.0001). Mortality ranged from 0.9 to 1.8% by subdistrict. Individual-level factors associated with death were older age, male sex, comorbidities and age <5 years during the first wave (adjusted OR (aOR)) 1.56, 95% CI 1.04 to 2.35; reference: age 20–29 years). Community-level factors associated with death were poverty (aOR for the poorer quarter 1.35, 95% CI 1.17 to 1.55; reference: wealthiest quarter) and high population density (aOR for the highest density 1.34, 95% CI 1.14 to 2.58; reference: the lowest). Healthcare factor associated with death was low vaccine coverage (aOR for the lowest coverage 1.25, 95% CI 1.13 to 1.38; reference: the highest). Conclusion In addition to individual risk factors, living in areas with high poverty and density, and low healthcare performance further increase the vulnerability of communities to COVID-19-associated death in urban low-resource settings

Transcriptome Reveals 1400-Fold Upregulation of APOA4-APOC3 and 1100-Fold Downregulation of GIF in the Patients with Polycythemia-Induced Gastric Injury

High-altitude polycythemia (HAPC) inducing gastric mucosal lesion (GML) is still out of control and molecular mechanisms remain widely unknown. To address the issues, endoscopy and histopathological analyses were performed. Meanwhile, microarray-based transcriptome profiling was conducted in the gastric mucosa from 3 pairs of healthy subjects and HAPC-induced GML patients. HAPC caused morphological changes and pathological damages of the gastric mucosa of GML patients. A total of 10304 differentially expressed genes (DEGs) were identified, including 4941 up-regulated and 5363 down-regulated DEGs in gastric mucosa of GML patients compared with healthy controls (fold change ≥2, P<0.01 and FDR <0.01). Particularly, apolipoprotein genes APOA4 and APOC3 were 1473-fold and 1468-fold up-regulated in GML patients compared with the controls. In contrast, gastric intrinsic factor (GIF) was 1102-fold down-regulated in GML patients compared with the controls. APOA4 (chr11:116691770-116691711), APOC3 (chr11:116703530-116703589) and GIF (chr11:59603362-59603303) genes are all located on chromosome 11. APOA4 and APOC3 act as an inhibitor of gastric acid secretion while gastric acid promotes ulceration. GIF deficiency activates a program of acute anemia, which may antagonize polycythemia while polycythemia raises the risk of GML. Therefore, the present findings reveal that HAPC-induced GML inspires the protection responses by up-regulating APOA4 and APOC3, and down-regulating GIF. These results may offer the basic information for the treatment of HAPC-induced gastric lesion in the future