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JAMA Network Open Oct 2023The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates...
IMPORTANCE
The combination of ceftriaxone and lansoprazole has been shown to prolong the corrected QT interval on electrocardiogram. However, it is unknown whether this translates to clinically important patient outcomes.
OBJECTIVE
To compare lansoprazole with another proton pump inhibitor (PPI) during ceftriaxone treatment in terms of risk for ventricular arrhythmia, cardiac arrest, and in-hospital mortality.
DESIGN, SETTING, AND PARTICIPANTS
A retrospective cohort study including adult medical inpatients receiving ceftriaxone with lansoprazole or another PPI in 13 hospitals in Ontario, Canada, was conducted from January 1, 2015, to December 31, 2021.
EXPOSURE
Lansoprazole during ceftriaxone treatment vs other PPIs during ceftriaxone treatment.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of ventricular arrhythmia or cardiac arrest that occurred after hospital admission. The secondary outcome was all-cause in-hospital mortality. Propensity-score weighting was used to adjust for covariates including hospital site, demographic characteristics, comorbidities, risk factors for ventricular arrhythmia, illness severity, admitting diagnoses, and concomitant medications.
RESULTS
Of the 31 152 patients hospitalized on internal medicine wards who were treated with ceftriaxone while receiving a PPI, 16 135 patients (51.8%) were male, and the mean (SD) age was 71.7 (16.0) years. The study included 3747 patients in the lansoprazole group and 27 405 patients in the other PPI group. Ventricular arrhythmia or cardiac arrest occurred in 126 patients (3.4%) within the lansoprazole group and 319 patients (1.2%) within the other PPI group. In-hospital mortality occurred in 746 patients (19.9%) within the lansoprazole group and 2762 patients (10.1%) in the other PPI group. After weighting using propensity scores, the adjusted risk difference for the lansoprazole group minus other PPI group was 1.7% (95% CI, 1.1%-2.3%) for ventricular arrhythmia or cardiac arrest and 7.4% (95% CI, 6.1%-8.8%) for in-hospital mortality.
CONCLUSIONS AND RELEVANCE
The findings of this cohort study suggest that combination therapy with lansoprazole and ceftriaxone should be avoided. More studies are needed to determine whether these findings could be replicated in other populations and settings.
Topics: Adult; Humans; Male; Aged; Female; Lansoprazole; Ceftriaxone; Cohort Studies; Retrospective Studies; Arrhythmias, Cardiac; Heart Arrest; Proton Pump Inhibitors; Inpatients; Ontario
PubMed: 37883084
DOI: 10.1001/jamanetworkopen.2023.39893 -
Clinical and Translational... Jul 2023Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Mirikizumab, a monoclonal antibody targeting the p19 subunit of interleukin (IL)-23, demonstrated efficacy and was well-tolerated in a phase 2 randomized clinical trial in patients with moderate-to-severe ulcerative colitis (UC) (NCT02589665). We explored gene expression changes in colonic tissue from study patients and their association with clinical outcomes.
METHODS
Patients were randomized to receive intravenous placebo or 3 mirikizumab induction doses. Patient biopsies were collected at baseline and week 12, and differential gene expression was measured using a microarray platform and compared in all treatment groups to determine differential expression values between baseline and week 12.
RESULTS
The greatest improvement in clinical outcomes and placebo-adjusted change from baseline in transcripts at week 12 was observed in the 200 mg mirikizumab group. Transcripts significantly modified by mirikizumab correlate with key UC disease activity indices (modified Mayo score, Geboes score, and Robarts Histopathology Index) and include MMP1, MMP3, S100A8, and IL1β. Changes in transcripts associated with increased disease activity were decreased after 12 weeks of mirikizumab treatment. Mirikizumab treatment affected transcripts associated with resistance to current therapies, including IL-1β, OSMR, FCGR3A and FCGR3B, and CXCL6, suggesting that anti-IL23p19 therapy modulates biological pathways involved in resistance to antitumor necrosis factor and Janus kinase inhibitors.
DISCUSSION
This is the first large-scale gene expression study of inflamed mucosa from patients with UC treated with anti-IL23p19 therapy. These results provide molecular evidence for mucosal healing from an extensive survey of changes in transcripts that improve our understanding of the molecular effects of IL-23p19 inhibition in UC.
Topics: Humans; Colitis, Ulcerative; Tumor Necrosis Factor Inhibitors; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal
PubMed: 36881820
DOI: 10.14309/ctg.0000000000000578 -
Journal of Crohn's & Colitis Oct 2023To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIMS
To evaluate the effect of mirikizumab, a p19-targeted anti-interleukin-23, on histological and/or endoscopic outcomes in moderately-to-severely active ulcerative colitis [UC].
METHODS
Endoscopic remission [ER], histological improvement [HI], histological remission [HR], histological-endoscopic mucosal improvement [HEMI], and histological-endoscopic mucosal remission [HEMR] were assessed at Week [W]12 [LUCENT-1: N = 1162, induction] and W40 [LUCENT-2: N = 544, maintenance] for patients randomised to mirikizumab or placebo. Analyses were performed to evaluate predictors of: HEMI at W12 with mirikizumab and HEMR at W40 in patients re-randomised to subcutaneous [SC] mirikizumab; associations between W12 histological/endoscopic endpoints and W40 outcomes in mirikizumab responders re-randomised to mirikizumab SC; and associations between W40 endoscopic normalisation [EN] with/without HR.
RESULTS
Significantly more patients treated with mirikizumab achieved HI, HR, ER, HEMI, and HEMR vs placebo [p <0.001], irrespective of prior biologic/tofacitinib failure [p <0.05]. Lower clinical baseline disease activity, female sex, no baseline immunomodulator use, and no prior biologic/tofacitinib failure were predictors of HEMI at W12 [p <0.05]. Corticosteroid use and longer disease duration were negative predictors of achieving HEMR at W40 [p <0.05]. W12 HI, HR, or ER was associated with W40 HEMI or HEMR [p <0.05]; ER at W12 was associated with clinical remission [CR] [p <0.05] and corticosteroid-free remission [CSFR] at W40 [p = 0.052]. HR and HEMR at W12 were associated with CSFR, CR, and symptomatic remission at W40. Alternate HEMR [EN + HR] at W40 was associated with bowel urgency remission at W40 [p <0.05].
CONCLUSIONS
Early resolution of endoscopic and histological inflammation with mirikizumab is associated with better UC outcomes. Clinicaltrials.gov: LUCENT-1, NCT03518086; LUCENT-2, NCT03524092.
Topics: Humans; Female; Colitis, Ulcerative; Inflammation; Adrenal Cortex Hormones; Biological Products; Remission Induction; Sulfonamides; Antibodies, Monoclonal, Humanized
PubMed: 37057827
DOI: 10.1093/ecco-jcc/jjad050 -
The American Journal of Gastroenterology Nov 2023In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are... (Randomized Controlled Trial)
Randomized Controlled Trial
Poliprotect vs Omeprazole in the Relief of Heartburn, Epigastric Pain, and Burning in Patients Without Erosive Esophagitis and Gastroduodenal Lesions: A Randomized, Controlled Trial.
INTRODUCTION
In the treatment of upper GI endoscopy-negative patients with heartburn and epigastric pain or burning, antacids, antireflux agents, and mucosal protective agents are widely used, alone or as add-on treatment, to increase response to proton-pump inhibitors, which are not indicated in infancy and pregnancy and account for significant cost expenditure.
METHODS
In this randomized, controlled, double-blind, double-dummy, multicenter trial assessing the efficacy and safety of mucosal protective agent Poliprotect (neoBianacid, Sansepolcro, Italy) vs omeprazole in the relief of heartburn and epigastric pain/burning, 275 endoscopy-negative outpatients were given a 4-week treatment with omeprazole (20 mg q.d.) or Poliprotect (5 times a day for the initial 2 weeks and on demand thereafter), followed by an open-label 4-week treatment period with Poliprotect on-demand. Gut microbiota change was assessed.
RESULTS
A 2-week treatment with Poliprotect proved noninferior to omeprazole for symptom relief (between-group difference in the change in visual analog scale symptom score: [mean, 95% confidence interval] -5.4, -9.9 to -0.1; -6.2, -10.8 to -1.6; intention-to-treat and per-protocol populations, respectively). Poliprotect's benefit remained unaltered after shifting to on-demand intake, with no gut microbiota variation. The initial benefit of omeprazole was maintained against significantly higher use of rescue medicine sachets (mean, 95% confidence interval: Poliprotect 3.9, 2.8-5.0; omeprazole 8.2, 4.8-11.6) and associated with an increased abundance of oral cavity genera in the intestinal microbiota. No relevant adverse events were reported in either treatment arm.
DISCUSSION
Poliprotect proved noninferior to standard-dose omeprazole in symptomatic patients with heartburn/epigastric burning without erosive esophagitis and gastroduodenal lesions. Gut microbiota was not affected by Poliprotect treatment. The study is registered in Clinicaltrial.gov (NCT03238534) and the EudraCT database (2015-005216-15).
Topics: Humans; Omeprazole; Heartburn; Anti-Ulcer Agents; Esophagitis; Proton Pump Inhibitors; Dyspepsia; Peptic Ulcer; Abdominal Pain; Treatment Outcome; Double-Blind Method
PubMed: 37307528
DOI: 10.14309/ajg.0000000000002360 -
Biomedicine & Pharmacotherapy =... Aug 2023Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available... (Review)
Review
Although a growing body of research has recently shown how crucial inflammation and infection are to all major diseases, several of the medications currently available on the market have various unfavourable side effects, necessitating the development of alternative therapeutic choices. Researchers are increasingly interested in alternative medications or active components derived from natural sources. Naringenin is a commonly consumed flavonoid found in many plants, and since it was discovered to have nutritional benefits, it has been utilized to treat inflammation and infections caused by particular bacteria or viruses. However, the absence of adequate clinical data and naringenin's poor solubility and stability severely restrict its usage as a medicinal agent. In this article, we discuss naringenin's effects and mechanisms of action on autoimmune-induced inflammation, bacterial infections, and viral infections based on recent research. We also present a few suggestions for enhancing naringenin's solubility, stability, and bioavailability. This paper emphasizes the potential use of naringenin as an anti-inflammatory and anti-infective agent and the next prophylactic substance for the treatment of various inflammatory and infectious diseases, even though some mechanisms of action are still unclear, and offers some theoretical support for its clinical application.
Topics: Humans; Flavanones; Anti-Inflammatory Agents; Inflammation; Anti-Infective Agents
PubMed: 37315435
DOI: 10.1016/j.biopha.2023.114990 -
JAMA Network Open Sep 2023Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Ranitidine, the most widely used histamine-2 receptor antagonist (H2RA), was withdrawn because of N-nitrosodimethylamine impurity in 2020. Given the worldwide exposure to this drug, the potential risk of cancer development associated with the intake of known carcinogens is an important epidemiological concern.
OBJECTIVE
To examine the comparative risk of cancer associated with the use of ranitidine vs other H2RAs.
DESIGN, SETTING, AND PARTICIPANTS
This new-user active comparator international network cohort study was conducted using 3 health claims and 9 electronic health record databases from the US, the United Kingdom, Germany, Spain, France, South Korea, and Taiwan. Large-scale propensity score (PS) matching was used to minimize confounding of the observed covariates with negative control outcomes. Empirical calibration was performed to account for unobserved confounding. All databases were mapped to a common data model. Database-specific estimates were combined using random-effects meta-analysis. Participants included individuals aged at least 20 years with no history of cancer who used H2RAs for more than 30 days from January 1986 to December 2020, with a 1-year washout period. Data were analyzed from April to September 2021.
EXPOSURE
The main exposure was use of ranitidine vs other H2RAs (famotidine, lafutidine, nizatidine, and roxatidine).
MAIN OUTCOMES AND MEASURES
The primary outcome was incidence of any cancer, except nonmelanoma skin cancer. Secondary outcomes included all cancer except thyroid cancer, 16 cancer subtypes, and all-cause mortality.
RESULTS
Among 1 183 999 individuals in 11 databases, 909 168 individuals (mean age, 56.1 years; 507 316 [55.8%] women) were identified as new users of ranitidine, and 274 831 individuals (mean age, 58.0 years; 145 935 [53.1%] women) were identified as new users of other H2RAs. Crude incidence rates of cancer were 14.30 events per 1000 person-years (PYs) in ranitidine users and 15.03 events per 1000 PYs among other H2RA users. After PS matching, cancer risk was similar in ranitidine compared with other H2RA users (incidence, 15.92 events per 1000 PYs vs 15.65 events per 1000 PYs; calibrated meta-analytic hazard ratio, 1.04; 95% CI, 0.97-1.12). No significant associations were found between ranitidine use and any secondary outcomes after calibration.
CONCLUSIONS AND RELEVANCE
In this cohort study, ranitidine use was not associated with an increased risk of cancer compared with the use of other H2RAs. Further research is needed on the long-term association of ranitidine with cancer development.
Topics: Female; Humans; Middle Aged; Male; Ranitidine; Cohort Studies; Thyroid Neoplasms; Histamine H2 Antagonists; Skin Neoplasms
PubMed: 37725377
DOI: 10.1001/jamanetworkopen.2023.33495 -
Journal of Psychosomatic Research Sep 2023This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
This is an investigation of the efficacy and safety of famotidine, a selective histamine H2 receptor antagonist, on improvement of cognitive impairment, depression and anxiety symptoms developing post-COVID-19, in a 12-week, randomized controlled trial.
METHODS
A total of 50 patients with a confirmed diagnosis of COVID-19 and a score ≤ 23 on the Mini-Mental State Examination (MMSE) test or a score ≤ 22 on the Montreal Cognitive Assessment (MoCA) were randomly assigned to either the famotidine (40 mg twice daily) or the placebo group. Changes in MMSE scores at weeks 6 and 12 were the primary outcome, while changes in other scales were the secondary outcomes. Participants and evaluators were blinded.
RESULTS
At weeks 6 and 12, patients in the famotidine group had significantly higher MMSE scores (p = 0.014, p < 0.001, respectively). Regarding the MoCA scale, the famotidine group had a significantly higher score at weeks 6 and 12 (p = 0.001, p < 0.001, respectively). Considering the HAM-D scale (Hamilton Depression Rating Scale), at weeks 6 and 12, the famotidine group experienced a larger reduction (p = 0.009, p = 0.02, respectively). Additionally, comparison of the HAM-A scale scores (Hamilton Anxiety Rating Scale) at weeks 6 and 12 showed a statistically significant larger reduction in the famotidine group (p = 0.04, p = 0.02, respectively). The two groups did not differ in the frequency of adverse effects.
CONCLUSION
Our study supports safety and efficacy of famotidine in treating cognitive impairment, depression and anxiety symptoms induced by COVID-19.
TRIAL REGISTRATION
This trial was registered at the Iranian registry of clinical trials (IRCT: www.irct.ir; registration number: IRCT20090117001556N138).
Topics: Humans; Famotidine; COVID-19; Iran; Histamine H2 Antagonists; Cognition; Double-Blind Method; Treatment Outcome
PubMed: 37327698
DOI: 10.1016/j.jpsychores.2023.111389 -
Journal of the International Society of... Dec 2023High-intensity exercise (HIE) can damage the musculotendon complex and impact the immune response, resulting in post-exercise inflammation. Sufficient rest and recovery... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
High-intensity exercise (HIE) can damage the musculotendon complex and impact the immune response, resulting in post-exercise inflammation. Sufficient rest and recovery will improve muscular resilience against future damaging bouts; however, HIE with minimal durations of rest is common in athletic competitions that facilitate persistent inflammation and immune dysregulation. Fucoidans are fucose-rich sulfated polysaccharides with demonstrated anti-inflammatory and pro-immune responses. Fucoidans may improve inflammation and immune responses, which may prove beneficial for individuals who regularly engage in repeated HIE. The research purpose was to investigate the safety and efficacy of fucoidans on inflammatory and immune markers following HIE.
METHODS
Eight male and eight female participants were randomized into a double-blind, placebo-controlled, counterbalanced, crossover design study and supplemented with 1 g/day fucoidan from (UPF) or placebo (PL) for 2 weeks. Supplementation periods concluded with HIE testing, followed by 1 week of washout. HIE involved one > 30 s Wingate anaerobic test (WAnT) and eight 10 s WAnT intervals. Blood was drawn pre-exercise, immediately post-exercise, 30 min, and 60 min post-exercise to assess immune and inflammatory markers. Blood markers, peak power (PP), and mean power (MP) were analyzed using a 2 (condition) × 4 (time) design. Significance was set at α = .05.
RESULTS
A time-by-condition interaction was observed for interleukin-6 ( = .01) and interleukin-10 ( = .008). Post hoc analysis revealed greater interleukin-6 and interleukin-10 concentrations at 30 min post HIE with UPF supplementation ( = .002 and = .005, respectively). No effects of condition were observed for all blood markers or performance outcomes with UPF supplementation ( > .05). Main effects of time were observed for white blood cells, red blood cells, red cell distribution width, mean platelet volume, neutrophils, lymphocytes, monocytes, eosinophils, basophils, natural killer cells, B and T-lymphocytes, CD4 and CD8 cells ( < .05).
DISCUSSION
No adverse events were reported throughout the study period, indicating a positive safety profile of UPF. While notable changes in biomarkers occurred up to 1 hr post HIE, few differences were observed between supplementation conditions. There did appear to be a modest effect of UPF on inflammatory cytokines potentially warranting further investigation. However, fucoidan supplementation did not influence exercise performance.
Topics: Humans; Male; Female; Interleukin-10; Interleukin-6; Polysaccharides; Inflammation; Dietary Supplements; Double-Blind Method
PubMed: 37331983
DOI: 10.1080/15502783.2023.2224751 -
JAMA Network Open Oct 2023Misoprostol-alone regimens for abortion may be more effective than previously thought. (Observational Study)
Observational Study
IMPORTANCE
Misoprostol-alone regimens for abortion may be more effective than previously thought.
OBJECTIVE
To estimate the effectiveness of medication abortion with misoprostol alone among individuals self-managing their abortion.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective observational cohort study of callers to safe abortion hotlines and accompaniment groups in Argentina, Nigeria, and Southeast Asia, participants were recruited between July 31, 2019, and October 1, 2020, prior to starting their medication abortion. Eligible participants were 13 years or older, had no contraindications to medication abortion, and were not currently bleeding. Participants completed a baseline and 2 follow-up surveys. The analysis was restricted to participants who reported using misoprostol alone and was performed between January 6, 2022 and September 8, 2023.
EXPOSURE
Self-managed medication abortion using misoprostol alone.
MAIN OUTCOMES AND MEASURES
The primary outcome was effectiveness, defined as participant self-report of complete abortion without procedural intervention, measured at 1 week and 3 weeks after taking misoprostol. Secondary outcomes included method safety, measured by self-report of experiencing warning signs (eg, heavy bleeding, pain, fever, discharge) indicative of a potential complication and by medical treatment (eg, blood transfusion, intravenous fluids, overnight hospital stay) indicative of a potential adverse event. Additional outcomes included length of bleeding and cramping, time to expulsion, and experience of adverse effects.
RESULTS
Among 1352 enrolled participants, 637 used misoprostol-alone regimens for abortion and were included in the analysis (591 [92.8%] from Nigeria, 45 [7.1%] from Southeast Asia, and 1 [0.2%] from Argentina; 384 [60.2%] aged 20-29 years; 317 [49.8%] with pregnancy durations <7 weeks and 205 [32.2%] with pregnancy durations between 7 and <9 weeks). At last follow-up after taking medication (median, 22 days; IQR, 21-26 days), 625 participants (98.1%; 95% CI, 96.7%-98.9%) had a complete abortion without procedural intervention. Potential adverse events were reported by 6 participants (0.9%; 95% CI, 0.4%-2.1%). Most participants experienced bleeding for less than 1 week (median, 4 days; IQR, 3-6 days) and expelled their pregnancy within 24 hours of starting the abortion process (median, 12 hours; IQR, 9-15 hours). Common side effects included nausea (335 participants [52.6%]), fever (232 [36.4%]), and diarrhea (181 [28.4%]).
CONCLUSIONS AND RELEVANCE
The findings suggest that misoprostol alone is a highly effective method of pregnancy termination. Future research should explore strategies to maximize the effectiveness of misoprostol alone in clinical and nonclinical settings.
Topics: Pregnancy; Female; Humans; Misoprostol; Prospective Studies; Mifepristone; Abortion, Induced; Abortion, Spontaneous
PubMed: 37889485
DOI: 10.1001/jamanetworkopen.2023.40042 -
Reproductive Health Aug 2023Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access. (Review)
Review
BACKGROUND
Most treatments for postpartum haemorrhage (PPH) lack evidence of effectiveness. New innovations are ubiquitous but have not been synthesized for ready access.
NARRATIVE REVIEW
Pubmed 2020 to 2021 was searched on 'postpartum haemorrhage treatment', and novel reports among 755 citations were catalogued. New health care strategies included early diagnosis with a bundled first response and home-based treatment of PPH. A calibrated postpartum blood monitoring tray has been described. Oxytocin is more effective than misoprostol; addition of misoprostol to oxytocin does not improve treatment. Heat stable carbetocin has not been assessed for treatment. A thermostable microneedle oxytocin patch has been developed. Intravenous tranexamic acid reduces mortality but deaths have been reported from inadvertent intrathecal injection. New transvaginal uterine artery clamps have been described. Novel approaches to uterine balloon tamponade include improvised and purpose-designed free-flow (as opposed to fixed volume) devices and vaginal balloon tamponade. Uterine suction tamponade methods include purpose-designed and improvised devices. Restrictive fluid resuscitation, massive transfusion protocols, fibrinogen use, early cryopreciptate transfusion and point-of-care viscoelastic haemostatic assay-guided blood product transfusion have been reported. Pelvic artery embolization and endovascular balloon occlusion of the aorta and pelvic arteries are used where available. External aortic compression and direct compression of the aorta during laparotomy or aortic clamping (such as with the Paily clamp) are alternatives. Transvaginal haemostatic ligation and compression sutures, placental site sutures and a variety of novel compression sutures have been reported. These include Esike's technique, three vertical compression sutures, vertical plus horizontal compression sutures, parallel loop binding compression sutures, uterine isthmus vertical compression sutures, isthmic circumferential suture, circumferential compression sutures with intrauterine balloon, King's combined uterine suture and removable retropubic uterine compression suture. Innovative measures for placenta accreta spectrum include a lower uterine folding suture, a modified cervical inversion technique, bilateral uterine artery ligation with myometrial excision of the adherent placenta and cervico-isthmic sutures or a T-shaped lower segment repair. Technological advances include cell salvage, high frequency focussed ultrasound for placenta increta and extra-corporeal membrane oxygenation.
CONCLUSIONS
Knowledge of innovative methods can equip clinicians with last-resort options when faced with haemorrhage unresponsive to conventional methods.
Topics: Female; Pregnancy; Humans; Postpartum Hemorrhage; Oxytocin; Misoprostol; Placenta; Hemostatics
PubMed: 37568196
DOI: 10.1186/s12978-023-01657-1