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Glepaglutide is a long-acting GLP-2 analog developed to improve intestinal absorption in short bowel syndrome (SBS) patients. We conducted a trial to establish efficacy and safety of glepaglutide in reducing parenteral support (PS) needs in SBS patients with intestinal failure (IF).
Objective
To analyse the effects of tracheostomy timing on COVID-19 outcomes by comparing mortality rates at different time points (7, 10 and 14 days).
Design
Systematic review and meta-analysis.
Data sources
PubMed, Embase, Cochrane Library, Web of Science and Scopus were searched from 31 August 2023 to 6 September 2023.
Primary and secondary outcomes measures
The primary outcome was short-term mortality, defined as intensive care unit (ICU) mortality, hospital mortality and 28-day or 30-day mortality. The secondary outcomes included mechanical ventilation duration, ICU and hospital days.
Results
Among 3465 patients from 12 studies, the 10-day subgroup analysis revealed higher mortality for earlier tracheostomy than for later tracheostomy (49.7% vs 32.6%, OR 1.91, 95% CI 1.37–2.65). No significant differences were observed at 7- and 14-day marks. Earlier tracheostomy was associated with shorter mechanical ventilation (mean difference=–7.35 days, 95% CI –11.63 to –0.38) and ICU stays (mean difference=–11.24 days, 95% CI –18.50 to –3.97) compared with later tracheostomy. Regarding hospital stay, the later tracheostomy group exhibited a trend towards longer-term inpatients, with no significant difference.
Conclusions
No significant difference in short-term mortality was observed between patients undergoing tracheostomy at 7 and 14 days; however, at 10 days, later tracheostomy resulted in a lower mortality rate. Accordingly, subtle timing differences may impact short-term results in COVID-19 patients. Considering that the later tracheostomy group had longer mechanical ventilation and ICU stays, additional research is required to determine an optimal timing that reduces mortality cost-effectively.
New England Journal of Medicine, Ahead of Print.
Objectives
To evaluate the cost-effectiveness of long-acting progestogens (LAP), including levonorgestrel-releasing intrauterine system (LNG-IUS) and depot-medroxyprogesterone acetate (DMPA), compared with the combined oral contraceptives pill (COCP) in preventing recurrence of endometriosis-related pain postsurgery.
Design
Within-trial economic evaluation alongside a multicentre, pragmatic, parallel-group, open-label, randomised controlled trial (Preventing Recurrence of Endometriosis by means of Long-Acting Progestogen Therapy trial).
Setting
Thirty-four UK hospitals recruiting participants from November 2015 to March 2019.
Patients
Four hundred and five women aged 16–45 years undergoing conservative endometriosis surgery.
Interventions
The ratio of 1:1 randomisation to receive LAPs (LNG-IUS or DMPA) or COCP.
Main outcome measures
The primary evaluation was a cost-utility analysis based on cost per quality-adjusted life-year (QALY) gained at 3 years. We adopted a UK National Health Service perspective. Secondary analyses in the form of cost-effectiveness analysis based on a range of outcomes were also undertaken.
Results
For the primary analysis, the COCP group incurred an additional cost of £533 (95% CI £52 to £983) per woman compared with LAPs. Treatment with COCP generated additional QALYs of 0.031 (95% CI –0.079 to 0.139) compared with the LAP group over 36-month follow-up. The incremental cost-effectiveness ratio for COCP compared with LAPs is therefore approximately £17 193 per QALY. The probabilistic sensitivity analysis suggested that there was a 54.7% probability that COCP would be cost-effective at the £20 000/QALY threshold. The secondary analyses revealed results more in favour of LAPs.
Conclusion
Although the COCP has a slightly higher probability of being cost-effective at £20 000/QALY threshold, there remains considerable uncertainty, with only marginal differences in outcomes between the two treatments. The lower rates of further surgery and second-line medical treatment for women allocated to LAPs may make this option preferable for some women.
Trial registration number
ISRCTN 97865475.
Research has found that in nearly 40% of opioid overdose deaths, documented bystanders could have potentially administered the lifesaving medicine naloxone. But in a promising update, a new study published in JAMA Network Open found that bystander-administered naloxone has “drastically increased” in recent years.
Introduction
Opioid therapy is often central to pain management during cancer care. However, opioid exposure and unaddressed psychological suffering jointly amplify opioid use disorder risk. Therefore, we iteratively developed a behavioural, individually delivered intervention to mitigate the risk of opioid use disorder during cancer care (Acceptance and Commitment Therapy Intervention when Opioids are Necessary (ACTION)).
Methods and analysis
This is a single-site, non-blinded, randomised, controlled pilot trial of ACTION compared with a waitlist control group. The aims of this study are to examine the feasibility (defined as an overall enrolment rate of ≥60% and a retention rate of >75%) and acceptability (assessed via patient-reported feedback in exit interviews and Client Satisfaction Questionnaire-8 ratings) of ACTION (primary outcomes) and to assess changes in participant-reported depression, anxiety and opioid misuse (secondary outcomes). Patients will be recruited from Dana-Farber Cancer Institute (Boston, Massachusetts, USA). The total number of patients completing the study will be 40. All patients will complete baseline and follow-up measures after 6 weeks. Patients randomly assigned to ACTION (n=20) will receive six weekly 30-min sessions delivered by a mental health provider either via telehealth or in-person. Patients assigned to the waitlist control group (n=20) will be offered the intervention on completion of their follow-up assessments, approximately 6 weeks (±2 weeks), following baseline.
Ethics and dissemination
This study is approved by the Dana-Farber/Harvard Cancer Center Institutional Review Board (Protocol #21-587). Participants provide either written or electronic informed consent on study approach and once enrolled, they can withdraw from the study at any time. Results will be published in peer-reviewed journals and presented at scientific meetings.
Trial registration number
NCT05643027.
Stroke, Ahead of Print. BACKGROUND:The tissue-based definition of transient ischemic attack, which requires the use of diffusion-weighted imaging (DWI), has limitations in its applicability to clinical practice. This contributes to the limited evidence regarding the risk of subsequent stroke and the associated predictors in the group of patients who are tissue-negative on DWI. Our aim was to assess the early and long-term prognoses of consecutive patients with tissue-negative transient ischemic attacks attended at an emergency department.METHODS:We performed a prospective cohort study of consecutive patients with neurologist-confirmed transient ischemic attack who were DWI-negative from January 2006 to June 2010. All patients underwent DWI on magnetic resonance imaging (4.0 [SD, 1.8] days) after the index event. The risk and predictors of stroke recurrence (SR) were determined at 1 year and after a median follow-up time of 6.6 (interquartile range, 5.0–9.6) years.RESULTS:A total of 370 patients were included. Previously, 244 patients with positive DWI results and 109 patients without magnetic resonance imaging performed were excluded. ABCD2 score >5 was determined in 95 (26.2%) patients; 15 (4.1%) patients experienced SR at 1 year and 18 (4.9%) beyond 1 year. Predictive models for short- and long-term prognoses were different. Large artery atherosclerosis cause (hazard ratio, 3.7 [95% CI, 1.2–11.0]) was the only predictor of 1-year SR. In contrast, male sex (hazard ratio, 4.17 [95% CI, 1.14–15.23];P=0.031), speech impairment (hazard ratio, 4.90 [95% CI, 1.05–22.93];P=0.044), and the presence of chronic microangiopathy expressed as Fazekas score of 3 (hazard ratio, 1.84 [95% CI, 1.15–2.97];P=0.012) were predictors of long-term SR follow-up.CONCLUSIONS:Patients with DWI-negative have a clinically important risk of recurrent vascular events and SR during medium- and long-term follow-ups. These patients warrant optimized secondary prevention to reduce their risk of recurrent vascular events over time. Predictors of SR varied over the follow-up.
Objectives
Opioid agonist, partial agonist and antagonist medications are used to treat opioid use disorder (OUD). This was the first omnibus narrative systematic review of the contemporary qualitative literature on patient experiences of receiving these medications.
Design
Narrative systematic review using the sample, phenomenon of interest, design, evaluation and research framework.
Data sources
PubMed, Embase and APA PsycINFO were searched between 1 January 2000 and 14 June 2023, with the addition of hand searches.
Eligibility criteria for selecting studies
Qualitative and mixed methods studies among adults with experience of receiving OUD treatment medication in community and criminal justice settings.
Data extraction and synthesis
One reviewer conducted searches using the pre-registered strategy. Two independent reviewers screened studies and assessed quality using the Consolidation Criteria for Reporting Qualitative tool. Identified reports were first categorised using domains from the addiction dimensions for assessment and personalised treatment (an instrument developed to guide OUD treatment planning), then by narrative synthesis.
Results
From 1129 studies, 47 reports (published between 2005 and 2023) were included. Five major themes (and nine subthemes) were identified: (1) expectations about initiating treatment (barriers to access; motivations to receive medication); (2) responses to medication induction and stabilisation; (3) experience of the dispensing pharmacy (attending; medication dispensing); (4) experiences of maintenance treatment (services; dose adjustment; personal and social functioning); and (5) social factors (integration and stigma) and experiences of discontinuing treatment. Together these themes reflected and endorsed the importance of patient-centred care and clinically integrated services. Further qualitative research in real-world settings is needed on extended-release buprenorphine given the relative novelty of this medication option.
Conclusions
A narrative systematic review of the qualitative studies of medications for OUD endorsed the importance of patient-centred care and clinically integrated services.
PROSPERO registration number
CRD42019139365.
This population-based retrospective cohort study uses linked health administrative databases to assess the risk of treatment discontinuation and mortality among adults in British Columbia, Canada, receiving buprenorphine/naloxone vs methadone for the treatment of opioid use disorder.
Circulation, Volume 150, Issue 22, Page 1815-1817, November 26, 2024.
The American Academy of Pediatrics (AAP) released its first clinical guidance on prescribing opioids for outpatient acute pain management to youth. Although it cautions against the dangers of rising opioid use disorder among children and teens, it also notes that a decrease in opioid prescription rates may leave some youth with pain that is not adequately treated.
With great interest, we read the paper by Ammer-Hermenau et al, which features a multicentre microbiome study that included buccal and rectal samples taken at admission from 450 patients with acute pancreatitis.1 Severe acute pancreatitis was post hoc defined as persistent organ failure and/or collections that required drainage. These patients were propensity score matched with patients with mild acute pancreatitis. Remarkedly, over-representation of 10 known short-chain fatty acid (SCFA)-producing bacteria was found in the severe group. The authors conclude that SCFAs might be associated with worse outcomes and speculate that the increased mortality that was observed in the intervention group of the Probiotics in Pancreatitis Trial (PROPATRIA) could be explained by SCFA producers in the probiotics formula.2 There are, however, some limitations to this study, and we believe the author’s statements are in need of nuance. First, the authors did not include a control group…
We appreciate the constructive dialogue from Cheng on our study’s findings.1 We agree that any clinical database study has limitations that necessitate careful interpretation of results. Manual medical records review is a logical next step to mitigate these shortcomings and allow a more thorough examination of each patient’s course. Nevertheless, we re-analysed our data in response to points raised. The analyses in our original paper suggest an elevated risk of undergoing an esophagogastroduodenoscopy (EGD) in patients treated with glucagon-like peptide-1 receptor agonists (GLP-1 RA) compared with control. As mentioned in our prior reply,2 we recognise that there is a potential diagnostic bias from this observation. We re-ran our cohorts and found that the rate of undergoing an EGD in the propensity-score matched cohort receiving short-acting GLP-1 RA was 6.13% compared with 5.22% in the matched control cohort (OR 1.185; 95% CI 1.131 to 1.241), reflecting the…
Objective
In patients with Crohn’s disease (CD) on combination therapy (infliximab and immunosuppressant) and stopping infliximab (cohort from the study of infliximab diSconTinuation in CrOhn’s disease patients in stable Remission on combined therapy with Immunosuppressors (STORI)), the risk of short-term (≤6 months) and mid/long-term relapse ( >6 months) was associated with distinct blood protein profiles. Our aim was to test the external validity of this finding in the SPARE cohort (A proSpective Randomized Controlled Trial comParing infliximAb-antimetabolites Combination Therapy to Anti-metabolites monotheRapy and Infliximab monothErapy in Crohn’s Disease Patients in Sustained Steroid-free Remission on Combination Therapy).
Design
In SPARE, patients with CD in sustained steroid-free clinical remission and on combination therapy were randomly allocated to three arms: continuing combination therapy, stopping infliximab or stopping immunosuppressant. In the baseline serum of the STORI and SPARE (arm stopping infliximab) cohorts, we studied 202 immune-related proteins. The proteins associated with time to relapse (univariable Cox model) were compared between STORI and SPARE. The discriminative ability of biomarkers (individually and combined in pairs) was evaluated by the c-statistic (concordance analysis) which was compared with C-reactive protein (CRP), faecal calprotectin and a previously validated model (CEASE).
Results
In STORI and SPARE, distinct blood protein profiles were associated with the risk of short-term (eg, high level: CRP, haptoglobin, interleukin-6, C-type lectin domain family 4 member C) and mid/long-term relapse (eg, low level: Fms-related tyrosine kinase 3 ligand, kallistatin, fibroblast growth factor 2). At external validation, the top 10 biomarker pairs showed a higher c-statistic than the CEASE model, CRP and faecal calprotectin in predicting short-term (0.76–0.80 vs 0.74 vs 0.71 vs 0.69, respectively) and mid/long-term relapse (0.66–0.68 vs 0.61 vs 0.52 vs 0.59, respectively).
Conclusion
In patients with CD stopping infliximab, we confirm that the risk of short-term and mid/long-term relapse is associated with distinct blood protein profiles showing the potential to guide infliximab withdrawal.
Trial registration number
NCT00571337 and NCT02177071.
We write in response to the Letter to the Editor by van den Berg et al1 commenting on our recent article ‘Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis’.2 We greatly appreciate the interest in our work and are grateful to clarify some aspects of the study. The primary endpoint of our study investigated whether microbial compositions can be employed as early predictors for severity of acute pancreatitis (AP). Patients with revised Atlanta classification III (RAC III) showed highly significant microbial differences compared with RAC I and RAC II. Further analysis revealed a higher abundance of species that are known producers of short-chain fatty acids (SCFA) in severe AP. Van den Berg et al mention the lack of a healthy control cohort, however, it is already known from previous studies that the microbial composition in stool samples of patients with AP…
Circulation, Volume 150, Issue Suppl_1, Page A4136932-A4136932, November 12, 2024. Introduction:Annually, over 500,000 Americans are hospitalized due to heart failure (HF), marking it as a major contributor to morbidity and mortality. It also poses a significant financial burden and leads to considerable losses in productivity.Objective:This study investigates the predictive accuracy of different socioeconomic metrics on the risk and outcomes of HF in Maryland.Methodology:A retrospective analysis of the Maryland State Inpatient Database (2016-2020) was conducted to assess the predictive accuracy of race/ethnicity, insurance status, household median income, and neighborhood poverty level (measured by the Distressed Communities Index) on the risk of heart failure-related hospital admissions and outcomes. Multivariate logistic regression models were also used to adjust for confounders.Result:During the study period, a total of 389,220 cases of HF were reported in the Maryland SID. The majority of these patients were white (56.8%) and female (51.1%), with a median age of 73 years (interquartile range [IQR] 62-82 years). The in-hospital mortality rate was 5.1%, while rates of atrial fibrillation, cardiac arrest and prolonged hospital stay were 34.4%, 0.3%, and 48.4%, respectively. Multivariate analysis revealed a substantial area under the ROC curve (AUC) indicating good model performance: 0.88 for predicting HF, 0.64 for atrial fibrillation, 0.64 for cardiac arrest 0.57 for prolonged hospital stays, 0.63 for mortality. Subgroup analyses showed variable predictiveness by race (AUC = 0.4378), payment method (AUC = 0.5754), income quartile (AUC = 0.5202), and deprivation composite score (AUC = 0.4751). Patients with private insurance had the highest risk of stress cardiomyopathy (odds ratio [OR] = 1.98; 95% confidence interval [CI] 1.70-2.29). Socioeconomic metrics, including neighborhood distress, showed varying predictive accuracy for the HF-related admissions and selected short-term outcomes, with the highest predictive accuracy for neighborhood distress on the risk of HF (AUC = 0.50, std: 0.006), atrial fibrillation (AUC = 0.48, std: 0.0007), cardiac arrest (AUC = 0.51, std: 0.007), and prolonged hospital stays (AUC = 0.53, std: 0.0005) and mortality (AUC = 0.50, std: 0.0015).Conclusion:Neighborhood poverty level demonstrates significant predictive power for assessing the risk of HF-related hospital admissions and the short-term outcomes among Maryland residents, exceeding factors like insurance and race/ethnicity.
