A pilot study evaluating high dose esomeprazole, bismuth subcitrate and amoxicillin for eradicating Helicobacter pylori infection in Iran.

BACKGROUND: Helicobacter pylori (H. pylori) is strongly associated with peptic ulcer disease and gastric cancer. We evaluated two triple therapy regimens comprising esomeprazole, high dose bismuth, and different doses of amoxicillin for first-line H. pylori eradication. MATERIALS AND METHODS: Two hundred patients with dyspepsia and naive H. pylori infection were randomly assigned into two groups (n = 100). Both groups were treated for 14 days similarly with esomeprazole (40 mg, twice daily) and bismuth subcitrate (240 mg, three times daily), but the dose of amoxicillin was varied between Groups A (750 mg) and B (1000 mg) three times daily. Treatment compliance and side effect were evaluated following the therapies and after 8 weeks, a negative test of stool H. pylori antigen confirmed eradication. RESULTS: The two groups were comparable with respect to sex and age. According to intention to treat analysis, eradication rates were 80% (95% CI: 77.2%-82.8%) and 90% (95% CI: 84.1%-95.9%) in A and B groups, respectively (p = 0.22). Per-protocol eradication rates were 87% (95% CI: 80.4%-93.6%) and 92.8% (95% CI: 87.7%-97.9%), respectively (p = 0.23). Severe adverse effects were 3% and 2%, respectively (p = 0.34). CONCLUSION: High dose esomeprazole, amoxicillin and bismuth achieved 92.8% cure rates per protocol in a country with a high background rate of resistance. Additional studies are needed to ascertain whether this therapy can be further improved. Until then, it can be recommended as a first-line H. pylori eradication in north of Iran.

Pilot studies of vonoprazan-containing Helicobacter pylori eradication therapy suggest Thailand may be more similar to the US than Japan.

BACKGROUND: Vonoprazan-containing Helicobacter pylori eradication is reliably effective in Japan. Its effectiveness in other countries remains unclear. Here, we examined vonoprazan-H. pylori therapies in Thailand. MATERIALS AND METHODS: This was pilot study of four different vonoprazan containing therapies. Subjects were randomized to: 14-day dual therapy (500 mg amoxicillin q.i.d. plus 20 mg vonoprazan b.i.d.), 14-day triple therapy (amoxicillin 1 g b.i.d., slow release clarithromycin-MR, 1 g daily plus vonoprazan 20 mg b.i.d.), 7-day high-dose vonoprazan triple therapy (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily and 60 mg vonoprazan once daily), and 14-day vonoprazan triple therapy plus bismuth (amoxicillin 1 g b.i.d., clarithromycin-MR 1 g daily, vonoprazan 20 mg b.i.d., and bismuth subsalicylate 1048 mg b.i.d.). Eradication was confirmed 4 weeks after therapy. Antimicrobial susceptibility and CYP3A4/5 genotyping were performed. RESULTS: One hundred H. pylori-infected patients (mean age 54.3 ± 13 years, 51% men) were randomized. All were CYP3A4 extensive metabolizers. Cure rates with both 14-day vonoprazan dual therapy and 14-day triple therapy were low: 66.7%; 95% CI = 43-85% (14/21), and 59.3%; 95% CI = 39-78%) (16/27), respectively. In contrast, 7-day high-dose vonoprazan triple therapy and 14-day vonoprazan triple plus bismuth proved effective 92.3%; 95% CI = 75%-99% (24/26) and 96.2%; 95% CI = 80%-100% (25/26), respectively. CONCLUSION: Both 14-day vonoprazan dual and triple therapy were ineffective for H. pylori eradication in Thailand. Higher dosage of vonoprazan, and/or the addition of bismuth may be required to achieve high H. pylori eradication rates. High-dose vonoprazan triple therapy and vonoprazan triple therapy adding bismuth might be used as first-line treatments in some regions with high efficacy irrespective of CYP3A4/5 genotype and clarithromycin resistance.

Cost Analysis of Intramedullary Screw versus Plate Osteosynthesis for Phalangeal and Metacarpal Fractures: An Observational Study.

Background: To compare the observed healthcare and societal costs of intramedullary screw (IMS) and plate fixation of extra-articular metacarpal and phalangeal fractures in a contemporary Australian context. Methods: A retrospective analysis, based on previously published data, was performed utilising information from Australian public and private hospitals, the Medicare Benefits Schedule (MBS) and the Australian Bureau of Statistics. Results: Plate fixation demonstrated longer surgical lengths (32 minutes, compared to 25 minutes), greater hardware costs (AUD 1,088 vs. AUD 355), more extended follow-up requirements (6.3 months, compared to 5 months) and higher rates of subsequent hardware removal (24% compared to 4.6%), resulting in an increased healthcare expenditure of AUD 1,519.41 in the public system, and AUD 1,698.59 in the private sector. Wage losses were estimated at AUD 15,515.78 when the fracture cohort is fixed by a plate, and AUD 13,542.43 when using an IMS - a differential of AUD 1,973.35. Conclusions: There is a substantial saving to both the health system and the patient when using IMS fixation over dorsal plating for the fixation of extra-articular metacarpal and phalangeal fractures. Level of Evidence: Level III (Cost Utility).

Identifying treatment heterogeneity in atrial fibrillation using a novel causal machine learning method.

BACKGROUND: Lifelong oral anticoagulation is recommended in patients with atrial fibrillation (AF) to prevent stroke. Over the last decade, multiple new oral anticoagulants (OACs) have expanded the number of treatment options for these patients. While population-level effectiveness of OACs has been compared, it is unclear if there is variability in benefit and risk across patient subgroups. METHODS: We analyzed claims and medical data for 34,569 patients who initiated a nonvitamin K antagonist oral anticoagulant (non-vitamin K antagonist oral anticoagulant (NOAC); apixaban, dabigatran, and rivaroxaban) or warfarin for nonvalvular AF between 08/01/2010 and 11/29/2017 from the OptumLabs Data Warehouse. A machine learning (ML) method was applied to match different OAC groups on several baseline variables including, age, sex, race, renal function, and CHA2DS2 -VASC score. A causal ML method was then used to discover patient subgroups characterizing the head-to-head treatment effects of the OACs on a primary composite outcome of ischemic stroke, intracranial hemorrhage, and all-cause mortality. RESULTS: The mean age, number of females and white race in the entire cohort of 34,569 patients were 71.2 (SD, 10.7) years, 14,916 (43.1%), and 25,051 (72.5%) respectively. During a mean follow-up of 8.3 (SD, 9.0) months, 2,110 (6.1%) of patients experienced the composite outcome, of whom 1,675 (4.8%) died. The causal ML method identified 5 subgroups with variables favoring apixaban over dabigatran; 2 subgroups favoring apixaban over rivaroxaban; 1 subgroup favoring dabigatran over rivaroxaban; and 1 subgroup favoring rivaroxaban over dabigatran in terms of risk reduction of the primary endpoint. No subgroup favored warfarin and most dabigatran vs warfarin users favored neither drug. The variables that most influenced favoring one subgroup over another included Age, history of ischemic stroke, thromboembolism, estimated glomerular filtration rate, Race, and myocardial infarction. CONCLUSIONS: Among patients with AF treated with a NOAC or warfarin, a causal ML method identified patient subgroups with differences in outcomes associated with OAC use. The findings suggest that the effects of OACs are heterogeneous across subgroups of AF patients, which could help personalize the choice of OAC. Future prospective studies are needed to better understand the clinical impact of the subgroups with respect to OAC selection.

Hybrid, High-Dose Dual and Bismuth Quadruple Therapies for First-Line Treatment of Helicobacter pylori Infection in Taiwan: A Multicenter, Open-Label, Randomized Trial.

INTRODUCTION: The study aimed to compare the efficacies and safety of 14-day hybrid therapy, 14-day high-dose dual therapy, and 10-day bismuth quadruple therapy in the first-line treatment of Helicobacter pylori infections. METHODS: In this multicenter, open-label, randomized trial, we recruited adult H. pylori -infected patients from 9 centers in Taiwan. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy, 14-day high-dose dual therapy, or 10-day bismuth quadruple therapy. Eradication status was determined by the 13 C-urea breath test. The primary outcome was the eradication rate of H. pylori assessed in the intention-to-treat population. RESULTS: Between August 1, 2018, and December 2021, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306; 95% confidence interval [CI] 88.4%-94.6%) for 14-day hybrid therapy, 83.3% (255/306; 95% CI 87.8%-95.0%) for 14-day high-dose dual therapy, and 90.2% (276/306; 95% CI 87.8%-95.0%) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference 8.2%; 95% CI 4.5%-11.9%; P = 0.002) and bismuth quadruple therapy (difference 6.9%; 95% CI 1.6%-12.2%; P = 0.012) were superior to high-dose dual therapy and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day high-dose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both P < 0.001). DISCUSSION: Fourteen-day hybrid therapy and 10-day bismuth quadruple therapy are more effective than 14-day high-dose dual therapy in the first-line treatment of H. pylori infection in Taiwan. However, high-dose dual therapy has fewer adverse effects than hybrid bismuth quadruple therapies.

Characterization of D-amino acids in colostral, transitional, and mature preterm human milk.

D-Amino acids are regulatory molecules that affect biological processes. Therefore, being able to accurately detect and quantify these compounds is important for understanding their impact on nutrition and health. There is a paucity of information regarding D-amino acids in human milk. We developed a fast method for simultaneous analysis of amino acid enantiomers in human milk using liquid chromatography with tandem mass spectrometry. The method enables the separation of 41 amino acids without chemical derivatization. Our results revealed that human milk from mothers of preterm infants contains concentrations of D-amino acids that range from 0.5 to 45% that of their L-counterparts and that levels of most D-amino acids decrease as the milk production matures. Moreover, we found that Holder pasteurization of milk does not cause racemization of L-amino acids. To our knowledge, this is the first study to describe percentages of D-amino acid levels in human milk; changes in D-amino acid concentration as the milk matures; and the effect of Holder pasteurization on D- and L-amino acid concentrations in human milk.

Temporal trends in the management of metacarpal and phalangeal fractures in the 21st century: an analysis of Australian population-based data.

BACKGROUND: Fractures of the hand, specifically the metacarpals and phalanges, are a common injury. Whilst many of these fractures can be treated non-operatively, a number of advances have led to the increase in popularity of surgical intervention. The aim of this study was to assess and describe trends in management of phalangeal and metacarpal fractures in Australia over the last two decades. METHODS: A review was conducted of the Medicare Benefits Scheme (MBS), specifically querying the item numbers pertaining to the management of metacarpal and phalanx fractures. Data was recorded as the incidence per 100 000 patients. RESULTS: Overall, there was a statistically significant decrease in the incidence of closed reduction of metacarpal and phalanx fractures, with a converse statistically significant increase in open reduction internal fixation. CONCLUSION: This study demonstrates that over the last 20 years, there has been a decrease in closed reduction of intra- and extra-articular phalangeal and metacarpal fractures, with a converse but smaller increase in open reduction and fixation. These trends are likely multi-factorial in aetiology, and should be monitored to guide resource allocation and health provision in the future.

Protective effects of NAMPT or MAPK inhibitors and NaR on Wallerian degeneration of mammalian axons.

Wallerian degeneration (WD) is a conserved axonal self-destruction program implicated in several neurological diseases. WD is driven by the degradation of the NAD+ synthesizing enzyme NMNAT2, the buildup of its substrate NMN, and the activation of the NAD+ degrading SARM1, eventually leading to axonal fragmentation. The regulation and amenability of these events to therapeutic interventions remain unclear. Here we explored pharmacological strategies that modulate NMN and NAD+ metabolism, namely the inhibition of the NMN-synthesizing enzyme NAMPT, activation of the nicotinic acid riboside (NaR) salvage pathway and inhibition of the NMNAT2-degrading DLK MAPK pathway in an axotomy model in vitro. Results show that NAMPT and DLK inhibition cause a significant but time-dependent delay of WD. These time-dependent effects are related to NMNAT2 degradation and changes in NMN and NAD+ levels. Supplementation of NAMPT inhibition with NaR has an enhanced effect that does not depend on timing of intervention and leads to robust protection up to 4 days. Additional DLK inhibition extends this even further to 6 days. Metabolite analyses reveal complex effects indicating that NAMPT and MAPK inhibition act by reducing NMN levels, ameliorating NAD+ loss and suppressing SARM1 activity. Finally, the axonal NAD+/NMN ratio is highly predictive of cADPR levels, extending previous cell-free evidence on the allosteric regulation of SARM1. Our findings establish a window of axon protection extending several hours following injury. Moreover, we show prolonged protection by mixed treatments combining MAPK and NAMPT inhibition that proceed via complex effects on NAD+ metabolism and inhibition of SARM1.

Neonatal encephalopathy plasma metabolites are associated with neurodevelopmental outcomes.

BACKGROUND: To investigate mechanisms of injury and recovery in neonatal encephalopathy (NE), we performed targeted metabolomic analysis of plasma using liquid chromatography with tandem mass spectrometry (LC/MS/MS) from healthy term neonates or neonates with NE. METHODS: Plasma samples from the NE (n = 45, day of life 0-1) or healthy neonatal (n = 30, ≥36 weeks gestation) cohorts had LC/MS/MS metabolomic profiling with a 193-plex targeted metabolite assay covering >366 metabolic pathways. Metabolite levels were compared to 2-year neurodevelopmental outcomes measured by the Bayley Scales of Infant and Toddler Development III (Bayley-III). RESULTS: Out of 193 metabolites, 57 met the pre-defined quality control criteria for analysis. Significant (after false discovery rate correction) KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways included aminoacyl-tRNA biosynthesis, arginine biosynthesis, and metabolism of multiple amino acids. Significant disease pathways included seizures. In regression models, histidine and C6 sugar amine were significantly associated with cognitive, motor, and language and betaine with cognitive and motor Bayley-III composite scores. The addition of histidine, C6 sugar amine, and betaine to a Sarnat score-based clinical regression model significantly improved model performance (Akaike information criterion and adjusted r2) for Bayley-III cognitive, motor, and language scores. CONCLUSIONS: Plasma metabolites may help to predict neurological outcomes in neonatal brain injury and enhance current clinical predictors. IMPACT: Plasma metabolites may help to predict neurological outcomes in NE and supplement current clinical predictors. Current metabolomics research is limited in terms of clinical application and association with long-term outcomes. Our study presents novel associations of plasma metabolites from the first 24 h of life and 2-year neurodevelopmental outcomes for infants with NE. Our metabolomics discovery provides insight into possible disease mechanisms and methods to rescue and/or supplement metabolic pathways involved in NE. Our metabolomics discovery of metabolic pathway supplementations and/or rescue mechanisms may serve as adjunctive therapies for NE.

Fourteen-day vonoprazan and low- or high-dose amoxicillin dual therapy for eradicating Helicobacter pylori infection: A prospective, open-labeled, randomized non-inferiority clinical study.

Background and aim: We previously reported that vonoprazan-amoxicillin (VA) dual therapy for 7 or 10 days is not satisfactorily efficacious for Helicobacter pylori (H. pylori) eradication. We aimed to explore the efficacy of VA dual therapy for 14 days as a first-line treatment for H. pylori infection. Methods: This was a single center, prospective, open-labeled, randomized non-inferiority clinical study conducted in China. Treatment naïve H. pylori infected patients were randomized into two groups: 20 mg vonoprazan (VPZ) b.i.d. in combination with low-dose (1000 mg b.i.d.) or high-dose (1000 mg t.i.d) amoxicillin for 14 days. 13C-urea breath tests were used to access the cure rate at least 4 weeks after treatment. Results: A total of 154 patients were assessed and 110 subjects were randomized. The eradication rate of VPZ with b.i.d. amoxicillin or t.i.d. amoxicillin for 14 days was 89.1% and 87.3% by intention-to-treat analysis, respectively, and 94.1% and 95.9% by per-protocol analysis, respectively. The eradication rate and incidence of adverse events were not different between the two groups. Conclusion: VPZ with b.i.d. or t.i.d. amoxicillin for 14 days provides satisfactory efficacy as a first-line treatment for H. pylori infection in China.

Comparison of Culture With Antibiogram to Next-Generation Sequencing Using Bacterial Isolates and Formalin-Fixed, Paraffin-Embedded Gastric Biopsies.

BACKGROUND & AIMS: The decline in Helicobacter pylori cure rates emphasizes the need for readily available methods to determine antimicrobial susceptibility. Our aim was to compare targeted next-generation sequencing (NGS) and culture-based H pylori susceptibility testing using clinical isolates and paired formalin-fixed, paraffin-embedded (FFPE) gastric biopsies. METHODS: H pylori isolates and FFPE tissues were tested for susceptibility to amoxicillin, clarithromycin, metronidazole, levofloxacin, tetracycline, and rifabutin using agar dilution and NGS targeted to 23S rRNA, gyrA, 16S rRNA, pbp1, rpoB and rdxA. Agreement was quantified using κ statistics. RESULTS: Paired comparisons included 170 isolates and FFPE tissue for amoxicillin, clarithromycin, metronidazole, and rifabutin and 57 isolates and FFPE tissue for levofloxacin and tetracycline. Agreement between agar dilution and NGS from culture isolates was very good for clarithromycin (κ = 0.90012), good for levofloxacin (κ = 0.78161) and fair for metronidazole (κ = 0.55880), and amoxicillin (κ = 0.21400). Only 1 isolate was resistant to tetracycline (culture) and 1 to rifabutin (NGS). Comparison of NGS from tissue blocks and agar dilution from isolates from the same stomachs demonstrated good accuracy to predict resistance for clarithromycin (94.1%), amoxicillin (95.9%), metronidazole (77%), levofloxacin (87.7%), and tetracycline (98.2%). Lack of resistance precluded comparisons for tetracycline and rifabutin. CONCLUSIONS: Compared with agar dilution, NGS reliably determined resistance to clarithromycin, levofloxacin, rifabutin, and tetracycline from clinical isolates and formalin-fixed gastric tissue. Consistency was fair for metronidazole and amoxicillin. Culture-based testing can predict treatment outcomes with clarithromycin and levofloxacin. Studies are needed to compare the relative ability of both methods to predict treatment outcomes for other antibiotics.

Validity of ICD-10-CM diagnoses to identify hospitalizations for serious infections among patients treated with biologic therapies.

PURPOSE: Identifying hospitalizations for serious infections among patients dispensed biologic therapies within healthcare databases is important for post-marketing surveillance of these drugs. We determined the positive predictive value (PPV) of an ICD-10-CM-based diagnostic coding algorithm to identify hospitalization for serious infection among patients dispensed biologic therapy within the FDA's Sentinel Distributed Database. METHODS: We identified health plan members who met the following algorithm criteria: (1) hospital ICD-10-CM discharge diagnosis of serious infection between July 1, 2016 and August 31, 2018; (2) either outpatient/emergency department infection diagnosis or outpatient antimicrobial treatment within 7 days prior to hospitalization; (3) inflammatory bowel disease, psoriasis, or rheumatological diagnosis within 1 year prior to hospitalization, and (4) were dispensed outpatient biologic therapy within 90 days prior to admission. Medical records were reviewed by infectious disease clinicians to adjudicate hospitalizations for serious infection. The PPV (95% confidence interval [CI]) for confirmed events was determined after further weighting by the prevalence of the type of serious infection in the database. RESULTS: Among 223 selected health plan members who met the algorithm, 209 (93.7% [95% CI, 90.1%-96.9%]) were confirmed to have a hospitalization for serious infection. After weighting by the prevalence of the type of serious infection, the PPV of the ICD-10-CM algorithm identifying a hospitalization for serious infection was 80.2% (95% CI, 75.3%-84.7%). CONCLUSIONS: The ICD-10-CM-based algorithm for hospitalization for serious infection among patients dispensed biologic therapies within the Sentinel Distributed Database had 80% PPV for confirmed events and could be considered for use within pharmacoepidemiologic studies.

Bismuth salts with versus without acid suppression for Helicobacter pylori infection: A transmission electron microscope study.

BACKGROUND: Bismuth oxychloride produced by interaction of bismuth compounds with gastric acid is believed to damage Helicobacter pylori. The effect of bismuth salts on H. pylori in the presence of strong acid suppression is unknown. This randomized trial aimed to determine effects of bismuth subcitrate on H. pylori with and without acid suppression. METHODS: H. pylori -positive participants were allocated (1:1:1) to receive (a) no treatment (control), (b) colloidal bismuth subcitrate (CBS, 125 mg/tab), or (c) CBS plus high-dose proton-pump inhibitor (PPI), esomeprazole 40 mg q.i.d. for 3 days. In the treatment groups, CBS was given: 1 dose, 1 hour before endoscopy, 1 dose, 4 hours before endoscopy, or q.i.d. 24 hours before endoscopy. The study end-points were evaluated using transmission electron microscopy to observe the morphological changes of H. pylori in antral and corpus biopsies. RESULTS: Twenty-seven H. pylori carriers were enrolled in this trial with qualitative end-points. In the no treatment group, active budding and replication of H. pylori were observed. In the CBS group, cellular swelling, vacuolization, structural degradation, and cell wall eruption of H. pylori were observed, with no apparent association with when the CBS was given. Among those receiving high-dose PPI-plus CBS or CBS only, there were no differences in number of H. pylori present or severity of bacterial damage whether CBS was given 1, 4, or 24 hours before endoscopy. CONCLUSIONS: Based on direct morphological evaluation, the toxic effect of CBS treatment on H. pylori was demonstrated independent of acid suppression with PPI.

The importance of regulating the education and training of Traditional Chinese Medicine practitioners and a potential role for ISO/TC 249.

As Traditional Chinese Medicine (TCM) transcends its cultural boundaries and becomes widely used in many countries around the world, one of the major risks to the growing use of TCM internationally is the damage caused to its reputation and to community safety when TCM practitioners are not adequately trained. Ensuring the quality and competency of TCM practitioners is a fundamental requirement. This paper covers (1) the current level of regulation of education and training of TCM practitioners particularly in countries with well developed health systems; (2) the progress of self regulatory standards for education and training developed by international organizations and (3) the potential role of ISO/TC 249 in assisting these initiatives.

Electrophysiological Evidence of Early Cortical Sensitivity to Human Conspecific Mimic Voice as a Distinct Category of Natural Sound.

Purpose From an anthropological perspective of hominin communication, the human auditory system likely evolved to enable special sensitivity to sounds produced by the vocal tracts of human conspecifics whether attended or passively heard. While numerous electrophysiological studies have used stereotypical human-produced verbal (speech voice and singing voice) and nonverbal vocalizations to identify human voice-sensitive responses, controversy remains as to when (and where) processing of acoustic signal attributes characteristic of "human voiceness" per se initiate in the brain. Method To explore this, we used animal vocalizations and human-mimicked versions of those calls ("mimic voice") to examine late auditory evoked potential responses in humans. Results Here, we revealed an N1b component (96-120 ms poststimulus) during a nonattending listening condition showing significantly greater magnitude in response to mimics, beginning as early as primary auditory cortices, preceding the time window reported in previous studies that revealed species-specific vocalization processing initiating in the range of 147-219 ms. During a sound discrimination task, a P600 (500-700 ms poststimulus) component showed specificity for accurate discrimination of human mimic voice. Distinct acoustic signal attributes and features of the stimuli were used in a classifier model, which could distinguish most human from animal voice comparably to behavioral data-though none of these single features could adequately distinguish human voiceness. Conclusions These results provide novel ideas for algorithms used in neuromimetic hearing aids, as well as direct electrophysiological support for a neurocognitive model of natural sound processing that informs both neurodevelopmental and anthropological models regarding the establishment of auditory communication systems in humans. Supplemental Material https://doi.org/10.23641/asha.12903839.

PPI-amoxicillin dual therapy for Helicobacter pylori infection: An update based on a systematic review and meta-analysis.

BACKGROUND AND AIMS: The efficacy of PPI-amoxicillin dual therapy (high-dose dual therapy) in the eradication of Helicobacter pylori is controversial. We aimed to investigate whether PPI-amoxicillin dual therapy is effective. METHODS: We searched several publication databases for randomized controlled trials (RCTs) that compared PPI-amoxicillin dual therapy with controls up to March 2019. Meta-analyses of eradication rates were performed using random-effects models. RESULTS: Data from twelve RCTs including 2249 patients suggested that PPI-amoxicillin dual therapy and the current mainstream guidelines-recommended therapies achieved similar efficacy (83.2% vs 85.3%, risk ratio [RR]: 1.00, 95% CI 0.97-1.03, intention-to-treat analysis), (87.5% vs 90.1%, RR: 0.98, 95% CI 0.95-1.02, per-protocol analysis), and compliance (94.3% vs 93.5%, RR: 1.11, 95% CI 0.78-1.59), but side effects were less likely in the dual therapy (12.9% vs 28.0%, RR: 0.53, 95% CI 0.37-0.76). Further subgroup analyses showed that the seven RCTs (1302 patients) that reported antimicrobial susceptibility test results also showed that PPI-amoxicillin dual therapy and the current guidelines-recommended therapies achieved similar efficacy, and PPI-amoxicillin dual therapy was as effective for rescue therapy (RR: 0.97, 95% CI 0.89-1.05) as for first-line treatment (RR: 0.97, 95% CI 0.93-1.02). CONCLUSIONS: Compared with the current mainstream guidelines-recommended therapies, PPI-amoxicillin dual therapy has the same efficacy and compliance, and generally PPI-amoxicillin dual therapy causes fewer side effects.

Incidence and characteristics of childhood- and youth-onset diabetes in the Qalandarabad area in northern Pakistan.

OBJECTIVES: Determine the types, incidence, mortality rate, and clinical status of youth diabetes at Bach Christian Hospital (BCH), Qalandarabad, Pakistan. METHODS: Analysis of incidence and mortality data of all patients (<25 year (y)) diagnosed from January 2014-June 2019, and also analysis of clinical status of patients < 25y seen in 2018/2019. RESULTS: Ninety-three patients were seen over the study period. Eighty-eight were type 1 diabetes (T1D), 51.1% female. Age of diagnosis was 0.8-24.5 years (y) (mean = 11.4 y, SD = 6.2y). 15.1% were 0-4y, 31.4% 5-9 y, 24.4% 10-14y, 19.8% 15-19y, and 9.3% 20-24y. Minimum incidence for the Mansehra tehsil administrative district was calculated as 1.0 per 100,000 population <15y/y, 1.2 per 100,000 < 20y/y and 1.1 per 100,000 < 25y/y; the degree of ascertainment could not be assessed. A further four patients were diagnosed with thiamine-responsive megaloblastic anaemia (TRMA), all male, three from the same consanguineous family, and were treated with high-dose thiamine. One other patient was diagnosed with type 2 diabetes. Three T1D and one TRMA patient died during the study period. The standardised mortality rate for T1D was 9.4, but vital status was unknown for 13 patients. The mean/median HbA1c of T1D patients seen in 2018/2019 was 9.1%/9.2% (76/77 mmol/mol). CONCLUSIONS: Minimum T1D incidence in Mansehra tehsil is double the previously reported value for Pakistan (from 1990 to 1999), although is still low compared to most other countries. Considering the limited resources available, patients attending BCH are achieving fair glycemic control. The TRMA cases show the importance of genetic testing in atypical cases.

14-Day High-Dose Amoxicillin- and Metronidazole-Containing Triple Therapy With or Without Bismuth as First-Line Helicobacter pylori Treatment.

BACKGROUND: Amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy had been shown to reliably achieve high eradication rates. The role of individual components remains undefined. AIM: To identify the additional benefit/role of bismuth in amoxicillin, metronidazole, proton pump inhibitor, bismuth quadruple therapy for Helicobacter pylori (H. pylori) treatment. METHODS: This was a non-inferiority factorial design trial. Treatment-naive H. pylori-infected subjects were randomly (1:1) assigned to receive 14-day amoxicillin- and metronidazole-containing triple therapy consisting of esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg both thrice daily with or without 220 mg bismuth twice a day. Six weeks after treatment, H. pylori eradication was assessed by 13C-urea breath test. Antimicrobial susceptibility was assessed by the twofold agar dilution method. RESULTS: From July 2018 to June 2019, a total of two hundred and sixteen subjects were randomized. Both therapies achieved high eradication rates. Per-protocol with bismuth = 97.9% (94/96, 95% CI 95.1-100%) and without bismuth = 94.7% (90/95, 95% CI 90.3-99.1%) (P = 0.43). Intent-to-treat analysis = 90.7% (98/108, 95% CI 85.2-96.2%) versus 88.9% (96/108, 95% CI 82.8-95.0%) with and without bismuth (P = 0.65). The two regimens were not inferior by intent-to-treat or per-protocol analyses. Metronidazole resistance did not affect the efficacy of either therapy. CONCLUSION: Neither the presence nor absence of bismuth or metronidazole resistance reduced the effectiveness of triple therapy containing esomeprazole 20 mg twice a day, amoxicillin 1 g, and metronidazole 400 mg thrice daily in this population. The clinical trial was registered with ClinicalTrials.gov, NCT03557437.