Efficacy of Helicobacter pylori eradication therapy for functional dyspepsia: updated systematic review and meta-analysis

ObjectiveFunctional dyspepsia (FD) is a chronic disorder that is difficult to treat. Helicobacter pylori may contribute to its pathophysiology. A Cochrane review from 2006 suggested that eradication therapy was beneficial, but there have been numerous randomised controlled trials (RCTs) published since. We evaluated impact of eradication therapy on both cure and improvement of FD, as well as whether any benefit was likely to arise from eradication of H. pylori.DesignWe searched the medical literature through October 2021 to identify RCTs examining efficacy of eradication therapy in H. pylori-positive adults with FD. The control arm received antisecretory therapy or prokinetics, with or without placebo antibiotics, or placebo alone. Follow-up was for ≥3 months. We pooled dichotomous data to obtain a relative risk (RR) of symptoms not being cured or symptoms not improving with a 95% CI. We estimated the number needed to treat (NNT).ResultsTwenty-nine RCTs recruited 6781 H. pylori-positive patients with FD. Eradication therapy was superior to control for symptom cure (RR of symptoms not being cured=0.91; 95% CI 0.88 to 0.94, NNT=14; 95% CI 11 to 21) and improvement (RR of symptoms not improving=0.84; 95% CI 0.78 to 0.91, NNT=9; 95% CI 7 to 17). There was no significant correlation between eradication rate and RR of FD improving or being cured (Pearson correlation coefficient=−0.23, p=0.907), but the effect was larger in patients with successful eradication of H. pylori than with unsuccessful eradication (RR=0.65; 95% CI 0.52 to 0.82, NNT=4.5, 95% CI 3 to 9). Adverse events (RR=2.19; 95% 1.10 to 4.37) and adverse events leading to withdrawal (RR=2.60; 95% CI 1.47 to 4.58) were more common with eradication therapy.ConclusionThere is high quality evidence to suggest that H. pylori eradication therapy leads to both cure and improvement in FD symptoms, although the benefit is modest.

Aspirin with Low-Dose Ticagrelor or with Low-Dose Rivaroxaban for Secondary Prevention: A Cost Per Outcome Analysis

Introduction: Secondary prevention of cardiovascular events among patients with diagnosed cardiovascular disease and high ischemic risk poses a significant challenge in clinical practice. The combinations of aspirin with low dose (LD) Ticagrelor or LD-Rivaroxaban have shown superiority in preventing major adverse cardiovascular events (MACE) than aspirin treatment alone. The comparative value for money of these two regimens remains unexplored.Methods: We analyzed each regimen's annual cost needed to treat (CNT) by multiplying the annualized number needed to treat (aNNT) by the annual cost of each drug. The aNNTs were based on outcome data from PEGASUS TIMI-54 and COMPASS trials. Scenario analyses were performed to overcome variances in terms of population risk. Costs were based on 2021 US prices. The primary outcome was defined as CNT to prevent one MACE across the two regimens. Secondary value analysis was performed for myocardial infarction (MI), stroke, and CV death as separate outcomes. Results: The aNNTs to prevent MACE with LD-Ticagrelor and with LD-Rivaroxaban were 229 [95% confidence interval (CI):141-734] and 147 (95%CI:104-252), respectively. At an annual cost of 3,618$ versus 4,308$, the corresponding CNTs were 828,478$ (95%CI:510,111$-2,655,471$) with LD-Ticagrelor and 633,270$ (95%CI:448,028$-1,085,607$) with LD-Rivaroxaban. LD-Rivaroxaban.Conclusion: Combining aspirin with LD-Rivaroxaban provides better value for money than with LD-Ticagrelor for secondary prevention of MACE.

Real World Evidence of Neutralizing Monoclonal Antibodies for Preventing Hospitalization and Mortality in COVID-19 Outpatients

Background: Neutralizing monoclonal antibodies (mAbs) are authorized for early symptomatic COVID-19 patients. Whether mAbs are effective against the SARS-CoV-2 Delta variant, among vaccinated patients, or for prevention of mortality remains unknown. Objective: To evaluate the effectiveness of mAb treatment in preventing progression to severe disease during the Delta phase of the pandemic and based on key baseline risk factors. Design, Setting, and Patients: Observational cohort study of non-hospitalized adult patients with SARS-CoV-2 infection from November 2020-October 2021, using electronic health records from a statewide health system plus state-level vaccine and mortality data. Using propensity matching, we selected approximately 2.5 patients not receiving mAbs for each patient who received mAbs. Exposure: Neutralizing mAb treatment under emergency use authorization Main Outcomes: The primary outcome was 28-day hospitalization; secondary outcomes included mortality and severity of hospitalization. Results: Of 36,077 patients with SARS-CoV-2 infection, 2,675 receiving mAbs were matched to 6,677 not receiving mAbs. Compared to mAb-untreated patients, mAb-treated patients had lower all-cause hospitalization (4.0% vs 7.7%; adjusted OR 0.48, 95%CI 0.38-0.60) and all-cause mortality (0.1% vs. 0.9%; adjusted OR 0.11, 95%CI 0.03-0.29) to day 28; differences persisted to day 90. Among hospitalized patients, mAb-treated patients had shorter hospital length of stay (5.8 vs. 8.5 days) and lower risk of mechanical ventilation (4.6% vs. 16.6%). Relative effectiveness was similar in preventing hospitalizations during the Delta variant phase (adjusted OR 0.35, 95%CI 0.25-0.50) and across subgroups. Lower number-needed-to-treat (NNT) to prevent hospitalization were observed for subgroups with higher baseline risk of hospitalization (e.g., multiple comorbidities (NNT=17) and not fully vaccinated (NNT=24) vs. no comorbidities (NNT=88) and fully vaccinated (NNT=81). Conclusion: Real-world evidence demonstrated mAb effectiveness in reducing hospitalization among COVID-19 outpatients, including during the Delta variant phase, and conferred an overall 89% reduction in 28-day mortality. Early outpatient treatment with mAbs should be prioritized, especially for individuals with highest risk for hospitalization.

Recovery Profiles of Sevoflurane and Desflurane with or without M-Entropy Guidance in Obese Patients: A Randomized Controlled Trial

Obesity increases the risk of prolonged emergence from general anesthesia due to the delayed release of anesthetic agents from body fat. This trial aimed to evaluate the effects of sevoflurane and desflurane along with anesthetic depth monitoring on emergence time from anesthesia in obese patients. Adults with a body mass index ≥ 30 kg·m−2 undergoing laparoscopic sleeve gastrectomy at a medical center were randomized into four groups: sevoflurane or desflurane anesthesia with or without M-Entropy guidance on anesthetic depth in a ratio of 1:1:1:1. In the M-Entropy guidance groups, the dosage of sevoflurane and desflurane was adjusted to achieve response and state entropy values between 40 and 60 during surgery. In the non-M-Entropy guidance groups, the dosage of anesthetics was titrated according to clinical signs. Primary outcome was time to spontaneous eye opening. A total of 80 participants were randomized. Compared to sevoflurane, desflurane anesthesia significantly reduced the time to spontaneous eye opening [mean difference (MD): −129 s; 95% confidence interval (CI): −211, −46], obeying commands (−160; −243, −77), tracheal extubation (−172; −266, −78), and leaving operating room (−148; −243, −54). M-Entropy guidance further reduced time to eye opening (MD: −142 s; 99.2% CI: −276, −8), tracheal extubation (−199; −379, −19), and leaving operating room (−190; −358, −23) in the desflurane but not the sevoflurane group. M-Entropy guidance significantly reduced the risk of agitation during emergence, i.e., risk difference: −0.275 (95% CI: −0.464, −0.086); and number needed to treat: 4. Compared to sevoflurane, using desflurane to maintain general anesthesia accelerated the return of consciousness in obese patients. M-Entropy guidance further hastened awakening in patients using desflurane and prevented emergence agitation.

Outpatient therapies for COVID-19: How do we choose?

Background: Several outpatient COVID-19 therapies have reduced hospitalization in randomized controlled trials. The choice of therapy may depend on drug efficacy, toxicity, pricing, availability, and access to administration infrastructure. To facilitate comparative decision making, we evaluated the efficacy of each treatment in clinical trials and then estimated the associated cost per hospitalization prevented. Methods: Wherever possible, we obtained relative risk for hospitalization from published randomized controlled trials. Otherwise, we extracted data from press releases, conference abstracts, government submissions, or preprints. If more than one study was published, the results were meta-analyzed. Using relative risk, we estimated the number needed to treat (NNT), assuming a baseline hospitalization risk of 5%. Drug pricing was based on Canadian formularies, government purchases, or manufacturer estimates. Administrative and societal costs were not included. Results will be updated online as new studies emerge or final publication numbers become available. Results: At a 5% risk of hospitalization the estimated NNTs were: 87 for colchicine, 80 for fluvoxamine, 72 for inhaled corticosteroids, 24 for nirmatrelvir/ritonavir, 25 for sotrovimab, 24 for remdesivir, 29 for casirivimab/imdevimab, 29 for bamlanivimab/etesevimab and 52 for molnupiravir. Colchicine, fluvoxamine, inhaled corticosteroids, and nirmatrelvir/ritonavir had cost per hospitalization prevented point estimates below the CIHI estimated cost of hospitalization ($23000). Interpretation: Canada is fortunate to have access to several effective outpatient therapies to prevent COVID-19 hospitalization. Given differences in efficacy, toxicity, cost and administration complexities, this assessment serves as one tool to help guide policy makers and clinicians in their treatment selection.

A 9-Year Teledermoscopy Service: Retrospective Service Review

Background A teledermoscopy service was established in January 2010, where patients attended nurse-led clinics for imaging of lesions of concern and remote diagnosis by a dermatologist. Objective The study aimed to review the number of visits, patient characteristics, the efficiency of the service, and the diagnoses made. Methods We evaluated the waiting time and diagnosis of skin lesions for all patient visits from January 1, 2010, to May 31, 2019. The relationships between patient characteristics and the diagnosis of melanoma were specifically analyzed. Results The teledermoscopy clinic was attended by 6479 patients for 11,005 skin lesions on 8805 occasions. Statistically significant risk factors for the diagnosis of melanoma/melanoma in situ were male sex, European ethnicity, and Fitzpatrick skin type 2. Attendance was maximal during 2015 and 2016. The seasonal variation in visits 2011-2018 revealed a consistent peak at the end of summer and a dip at the end of winter. In the year 2010, 306 patients attended; 76% (233/306) of these were discharged to primary care and 24% (73/306) were referred to hospital for specialist assessment. For patients diagnosed by the dermatologist with suspected melanoma from January 1, 2010, to May 31, 2019, the median waiting time for an imaging appointment was 44.5 days (average 57.9 days, range 8-218 days). The most common lesions diagnosed were benign naevus (2933/11,005, 27%), benign keratosis (2576/11,005, 23%), and keratinocytic cancer (1707/11,005, 15%); melanoma was suspected in 5% (507/11,005) of referred lesions (Multimedia Appendix 1). The positive predictive value of melanoma/melanoma in situ was 61.1% (320 true positives and 203 false positives). The number needed to treat (ie, the ratio of the total number of excisions to the number with a histological diagnosis of melanoma/melanoma in situ) was 2.02. Conclusions Diagnoses were comparable to the experience of other teledermoscopy services. Teledermoscopy using a nurse-led imaging clinic can provide efficient and convenient access to dermatology by streamlining referrals to secondary care and prioritizing patients with skin cancer for treatment. Conflicts of Interest None declared.

Evaluating the number of unvaccinated people needed to exclude to prevent SARS-CoV-2 transmissions

BackgroundVaccine mandates and vaccine passports (VMVP) for SARS-CoV-2 are thought to be a path out of the pandemic by increasing vaccination through coercion and excluding unvaccinated people from different settings because they are viewed as being at significant risk of transmitting SARS-CoV-2. While variants and waning efficacy are relevant, SARS-CoV-2 vaccines reduce the risk of infection, transmission, and severe illness/hospitalization in adults. Thus, higher vaccination levels are beneficial by reducing healthcare system pressures and societal fear. However, the benefits of excluding unvaccinated people are unknown.MethodsA method to evaluate the benefits of excluding unvaccinated people to reduce transmissions is described, called the number needed to exclude (NNE). The NNE is analogous to the number needed to treat (NNT=1/ARR), except the absolute risk reduction (ARR) is the baseline transmission risk in the population for a setting (e.g., healthcare). The rationale for the NNE is that exclusion removes all unvaccinated people from a setting, such that the ARR is the baseline transmission risk for that type of setting, which depends on the secondary attack rate (SAR) typically observed in that type of setting and the baseline infection risk in the population. The NNE is the number of unvaccinated people who need to be excluded from a setting to prevent one transmission event from unvaccinated people in that type of setting. The NNE accounts for the transmissibility of the currently dominant Delta (B.1.617.2) variant to estimate the minimum NNE in six types of settings: households, social gatherings, casual close contacts, work/study places, healthcare, and travel/transportation. The NNE can account for future potentially dominant variants (e.g., Omicron, B.1.1.529). To assist societies and policymakers in their decision-making about VMVP, the NNEs were calculated using the current (mid-to-end November 2021) baseline infection risk in many countries.FindingsThe NNEs suggest that at least 1,000 unvaccinated people likely need to be excluded to prevent one SARS-CoV-2 transmission event in most types of settings for many jurisdictions, notably Australia, California, Canada, China, France, Israel, and others. The NNEs of almost every jurisdiction examined are well within the range of the NNTs of acetylsalicylic acid (ASA) in primary prevention of cardiovascular disease (CVD) (≥ 250 to 333). This is important since ASA is not recommended for primary prevention of CVD because the harms outweigh the benefits. Similarly, the harms of exclusion may outweigh the benefits. These findings depend on the accuracy of the model assumptions and the baseline infection risk estimates.ConclusionsVaccines are beneficial, but the high NNEs suggest that excluding unvaccinated people has negligible benefits for reducing transmissions in many jurisdictions across the globe. This is because unvaccinated people are likely not at significant risk – in absolute terms – of transmitting SARS-CoV-2 to others in most types of settings since current baseline transmission risks are negligible. Consideration of the harms of exclusion is urgently needed, including staffing shortages from losing unvaccinated healthcare workers, unemployment/unemployability, financial hardship for unvaccinated people, and the creation of a class of citizens who are not allowed to fully participate in many areas of society.RegistrationCRD42021292263FundingThis study received no grant from any funding agency, commercial, or not-for-profit sectors. It has also received no support of any kind from any individual or organization. BH is supported by a personal research grant from the University of Wroclaw within the “Excellence Initiative – Research University” framework and by a scholarship from the Polish Ministry of Education and Science. None of these institutions were involved in this research and did not fund it directly.Competing interestsThe authors have no competing interests to declare.Ethical approvalNot applicable. All the work herein was performed using publicly available data.Data reportingThe data used in this work are available at https://tinyurl.com/4m8mm4jh and https://decision-support-tools.com/.

Does conventional specimen radiography after neoadjuvant chemotherapy of breast cancer help to reduce the rate of second surgeries?

Purpose This is the first study to systematically evaluate the diagnostic accuracy of intraoperative specimen radiography on margin level and its potential to reduce second surgeries in patients treated with neoadjuvant chemotherapy. Methods This retrospective study included 174 cases receiving breast conserving surgery (BCS) after neoadjuvant chemotherapy (NACT) of primary breast cancer. Conventional specimen radiography (CSR) was performed to assess potential margin infiltration and recommend an intraoperative re-excision of any radiologically positive margin. The histological workup of the specimen served as gold standard for the evaluation of the accuracy of CSR and the potential reduction of second surgeries by CSR-guided re-excisions. Results 1044 margins were assessed. Of 47 (4.5%) histopathological positive margins, CSR identified 9 correctly (true positive). 38 infiltrated margins were missed (false negative). This resulted in a sensitivity of 19.2%, a specificity of 89.2%, a positive predictive value (PPV) of 7.7%, and a negative predictive value (NPV) of 95.9%. The rate of secondary procedures was reduced from 23 to 16 with a number needed to treat (NNT) of CSR-guided intraoperative re-excisions of 25. In the subgroup of patients with cCR, the prevalence of positive margins was 10/510 (2.0%), PPV was 1.9%, and the NNT was 85. Conclusion Positive margins after NACT are rare and CSR has only a low sensitivity to detect them. Thus, the rate of secondary surgeries cannot be significantly reduced by recommending targeted re-excisions, especially in cases with cCR. In summary, CSR after NACT is inadequate for intraoperative margin assessment but remains useful to document removal of the biopsy site clip.

A 9-Year Teledermoscopy Service: Retrospective Service Review (Preprint)

BACKGROUND A teledermoscopy service was established in January 2010, where patients attended nurse-led clinics for imaging of lesions of concern and remote diagnosis by a dermatologist. OBJECTIVE The study aimed to review the number of visits, patient characteristics, the efficiency of the service, and the diagnoses made. METHODS We evaluated the waiting time and diagnosis of skin lesions for all patient visits from January 1, 2010, to May 31, 2019. The relationships between patient characteristics and the diagnosis of melanoma were specifically analyzed. RESULTS The teledermoscopy clinic was attended by 6479 patients for 11,005 skin lesions on 8805 occasions. Statistically significant risk factors for the diagnosis of melanoma/melanoma in situ were male sex, European ethnicity, and Fitzpatrick skin type 2. Attendance was maximal during 2015 and 2016. The seasonal variation in visits 2011-2018 revealed a consistent peak at the end of summer and a dip at the end of winter. In the year 2010, 306 patients attended; 76% (233/306) of these were discharged to primary care and 24% (73/306) were referred to hospital for specialist assessment. For patients diagnosed by the dermatologist with suspected melanoma from January 1, 2010, to May 31, 2019, the median waiting time for an imaging appointment was 44.5 days (average 57.9 days, range 8-218 days). The most common lesions diagnosed were benign naevus (2933/11,005, 27%), benign keratosis (2576/11,005, 23%), and keratinocytic cancer (1707/11,005, 15%); melanoma was suspected in 5% (507/11,005) of referred lesions (<xref ref-type="supplementary-material" rid="app1">Multimedia Appendix 1</xref>). The positive predictive value of melanoma/melanoma in situ was 61.1% (320 true positives and 203 false positives). The number needed to treat (ie, the ratio of the total number of excisions to the number with a histological diagnosis of melanoma/melanoma in situ) was 2.02. CONCLUSIONS Diagnoses were comparable to the experience of other teledermoscopy services. Teledermoscopy using a nurse-led imaging clinic can provide efficient and convenient access to dermatology by streamlining referrals to secondary care and prioritizing patients with skin cancer for treatment.

O-B01 Role of Ursodeoxycholic acid in prevention of gallstones formation in bariatric patients: need to amend recent BOMSS guidelines

Background During rapid weight-loss phase following bariatric procedures, biliary cholesterol homeostasis is altered leading to increased propensity to gallstone formation. Incidence of gallstone formation following bariatric procedures is shown to be 10-38%. There is no consensus regarding its prevention and current BOMSS guidelines do not address this issue. This meta-analysis aims to pool high level evidence (RCTs) to assess efficacy of Ursodeoxycholic acid (UDCA) in reducing risk of gallstone formation in this cohort of patients and the need for revision of current guidelines. Methods A systematic literature search was performed using electronic databases (Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, PROSPERO and Google Scholar) in line with PRISMA guidelines. Only randomised controlled trials were included without restrictions on study language, year, status of publication and patient’s age. Meta-analysis was performed using Review Manager Software to calculate pooled risk ratios (RR) using random-effects model. Results Fifteen trials were included (3952 patients analysed, 2487 in UDCA and 1465 in placebo group). The overall rate of gallstone formation was 16.0% (6.4% in UDCA vs 31.4% in placebo group). Trials included various bariatric procedures (SG/RYGB/OAGB/AGB/Gastroplasty). UDCA dose ranged from 300 to 1200mg per day. UDCA significantly reduced the risk of post-operative gallstone formation (3952 patients, RR 0.24, 95% CI 0.16-0.37, p &lt; 0.0001). The absolute risk reduction and number needed to treat (NNT) were 25% and 4 respectively. Conclusions Oral Ursodeoxycholic acid treatment following restrictive bariatric surgical procedures significantly reduces the risks of gallstone formation. As such, its regular use in first 6 months (rapid weight-loss phase) can significantly reduce the risk of complications associated with gallstones. Such treatment would be cost effective and benefit 1 in 4 patients. There is significant evidence available on benefits of using UDCA in post-operative bariatric patients and that this should be added to the recent BOMSS guidelines.