Current Medical Research and Opinion最新文献

Objective: Web resources can contain high-quality data relevant to peer-reviewed medical publications. However, their online location may change or disappear with time. As medical publication professionals, we are concerned with the ephemeral nature of web resources and the associated qualitative impact on publication integrity of referencing such resources.

Methods: Time-dependence of the phenomenon was probed using a dataset of reference lists from open and free access articles published in 2018. Each reference list was manually screened to tally the number of web pages no longer accessible. The analysis was repeated yearly from 2021 to 2023. Additionally, a set of proofs was analyzed to investigate the proportion of cited web references already inaccessible at publication. A third dataset, consisting of modeling articles published in 2018-2023, was used to quantify -at a single timepoint- the share of web resources cited as model inputs that were inaccessible.

Results: The proportion of inaccessible web resources increased on average from 27.2% to 41.9% three to five years post publication (n = 992 articles), respectively. One out of four analyzed proofs cited at least one inaccessible web resource (n = 50). Five years after publication, 26.1% of web resources used as model inputs were no longer accessible, with one in three modeling articles being impacted (n = 61).

Conclusion: The issue of inaccessible web resources cited in peer-reviewed medical publications is of great concern due to the fast pace and potential impact on research reproducibility. These findings call for the definition of best practices involving all stakeholders and the deployment of robust archiving solutions.

Objective: To assess efficacy and safety of fezolinetant in women unsuitable for hormone therapy (HT), using pooled SKYLIGHT 1 and 2 data.

Methods: SKYLIGHT 1 and 2 were double-blind, placebo-controlled studies of once-daily placebo, fezolinetant 30 mg or 45 mg for 12 weeks in women aged ≥40-≤65 years with moderate to severe vasomotor symptoms (VMS; average ≥7 hot flashes/d), followed by a double-blind, non-controlled extension period for 40 weeks. The HT unsuitable group comprised 4 mutually exclusive subgroups, categorized using the following hierarchy: contraindicated; caution; stopper for medical concerns; averse.

Results: A total of 1,022 participants received ≥1 dose of study medication (fezolinetant 30 mg, n = 339; fezolinetant 45 mg, n = 341). Improvement was seen for the HT unsuitable group in frequency and severity of moderate to severe VMS from baseline to weeks 4 and 12 (mean difference [95% CI] fezolinetant 45 mg vs. placebo: -2.55; 95% CI, -3.29 to -1.80; p < .001 at week 12). Sleep disturbance, measured by Patient-Reported Outcomes Measurement Information System Sleep Disturbance-Short Form 8b (PROMIS-SD SF 8b) total score, improved by weeks 4 and 12 (mean difference [95% CI] fezolinetant 45 mg vs. placebo at week 12: -1.60; 95% CI, -2.71 to -0.49; p = .005). Fezolinetant was well tolerated in the HT unsuitable group, with treatment-emergent adverse events in 39.4% of participants receiving fezolinetant 45 mg vs. 41.3% receiving placebo.

Conclusion: This pooled analysis demonstrated efficacy of fezolinetant vs. placebo in reducing frequency and severity of VMS due to menopause in participants unsuitable for HT.

Clinical trial registration: SKYLIGHT 1 - ClinicalTrials.gov, NCT04003155; https://clinicaltrials.gov/ct2/show/NCT04003155 (conducted between July 2019 and August 2021); SKYLIGHT 2 - ClinicalTrials.gov, NCT04003142; https://clinicaltrials.gov/ct2/show/NCT04003142 (conducted between July 2019 and April 2021).

Patients with ultra rare cancers have a high unmet medical need for the development of safe and effective treatments. To advance cancer drug development is often considered economically unattractive, and usually infeasible with the use of traditional paradigms. Compounding the challenges, evolving scientific understanding of the molecular biology of cancers has resulted in further subdivision of rare cancers into small molecularly defined subsets that may be eligible for targeted therapies. Indeed, research in oncology has undergone an evolution due to advances in biomarker discovery and drug target innovation moving towards a more personalized medicine and effective approach to cancer treatment. These therapies have shown remarkable efficacy with better disease management and brought a higher quality of life for cancer patients. Given the rarity of the diseases, standard randomized controlled trials may not be feasible, and innovative study designs and statistical methods should be applied to evaluate new treatments. To this aim, regulatory agencies have developed guidelines to introduce flexibility in planning of clinical trials, including new adaptive designs, use of real-world data, and surrogate endpoints. This commentary aims at reporting challenges on the evaluation of new treatments for ultra rare cancers with a focus on innovative trial designs, statistical methods, and managing of patients as these cancers are often poorly understood, have limited clinical data, and may require specialized treatment approaches.

Objective: Pneumonia continues to be one of the leading causes of death. During the COVID pandemic, pre-existing anticoagulant therapy with direct oral anticoagulants (DOACs) appeared to be beneficial. The present study aimed to investigate the impact of pre-existing DOAC therapy on mortality from community-acquired, non-COVID pneumonia.

Methods: The study utilized data from the eICU Collaborative Research Database, a comprehensive, multi-institutional critical care database. We included all adult patients with community-acquired pneumonia, selecting for patients with a primary admission diagnosis of pneumonia or pulmonary sepsis who were admitted to the ICU <24 h after admission to the hospital. To adjust for confounders, we performed propensity score matching, matching patients receiving DOACs to an equivalent cohort of patients not receiving DOAC therapy. Our primary outcome was overall survival. Secondary outcomes included all-cause in-hospital mortality, all-cause in-ICU mortality, intubation within 24 h following ICU admission, incidence of acute kidney injury and renal replacement therapy, vasopressor administration, and mechanical ventilation days.

Results: Our final matched cohort included 198 DOAC patients matched to 594 patients without DOAC therapy. Survival was significantly higher in DOAC patients with a hazard ratio of 0.56 [95% CI = 0.36-088]. Both all-cause in-unit mortality (6.1% [95% CI = 2.7-9.4%] vs. 13.3% [95% CI = 10.6-16.0%], p = 0.008) and all-cause in-hospital mortality (11.6% [95% CI = 7.2-16.1%] vs. 19.7% [95% CI = 16.5-22.9%], p = 0.013) were significantly lower in patients receiving DOACs.

Conclusion: This study demonstrates a positive association between the pre-existing intake of direct oral anticoagulants and the survival of community acquired pneumonia. Future prospective studies should evaluate supportive therapy with DOACs.

Objective: Patient-Reported Outcome (PRO) measures supported by a severity algorithm may serve as a decision aid for triage and consultation in follow-up of patients with endometriosis. In a new follow-up regime, patients filled out an endometriosis-specific questionnaire (EQ) at home before outpatient consultation (tele-Patient-Reported Outcome Measures; telePROM). A severity algorithm was assigned patients' answers using a color code thereby reflecting the need of clinical attention. Our study aimed to assess the test-retest reliability of the severity algorithm and of the single items as well as to evaluate the face- and content validity of the EQ.

Methods: The study was carried out in a referral endometriosis clinic at a Danish University Hospital. The validation was based on an initial version of the EQ, which was adjusted simultaneously with its severity algorithm, to meet the purpose of this study. Reliability was assessed by a test-retest setting of the questionnaire including patients with endometriosis, ≥ 18 years and Danish speaking. Kappa statistics and interclass correlation analyses were applied to assess test-retest reliability. Face- and content validity was explored by focus group interviewing of patients.

Results: In total, 14 patients answered the questionnaire twice. Results indicate that the EQ demonstrated substantial reliability in three out of five domain indicators in the severity algorithm and 65% of items with kappa values above 0.60. Further, focus-group interview of five patients resulted in adding an open-ended question regarding important issues to discuss at the consultation.

Conclusion: TelePROM in outpatient follow-up of endometriosis is feasible as patients viewed the questionnaire relevant for their clinical follow-up. Yet, due to the small sample size results should be interpreted with caution. Further validation of the EQ is recommended.

Objective: Colorectal cancer (CRC) poses significant mortality risks, particularly among Black individuals, who experience the highest CRC incidence and mortality rates in the U.S. This study examined adherence to multi-target stool DNA (mt-sDNA) testing in this population.

Methods: This retrospective cohort analysis used Exact Sciences Laboratories (ESL)-linked claims data from January 2017 to December 2023 on Black patients in the U.S. aged 45 and older. High-risk individuals, those with payers other than commercial plans, managed care organizations, Medicare Advantage, Medicaid, or Medicare, and individuals with mt-sDNA prescriptions outside the study period were excluded. Adherence was defined as the percentage of patients returning the test kit with valid results within 365 days of shipment. Logistic regression analysis was used to identify factors associated with adherence.

Results: Among 434,951 patients included in the study, the overall adherence to mt-sDNA testing was 62.0% (N = 266,981), with a mean time to adherence of 27.6 days (SD = 44.17) Females, older adults (76+ years), and rural residents had higher adherence than males, younger adults, and metropolitan patients (ORs = 1.05; all p < 0.001), respectively. Patients with orders from GI specialists had higher adherence than other prescribing clinicians (NP/PA: OR = 0.39, OB/GYN: OR = 0.54, Other: OR = 0.38, PCP: OR = 0.50; all p < 0.001). Digital outreach, especially SMS and email combination, was also associated with higher adherence (OR = 1.25, p < 0.001).

Conclusions: This large, national study found a 62.0% adherence rate to mt-sDNA testing among Black individuals. Higher adherence was associated with being female, older age, rural residence, and digital outreach. While the findings highlight the promise of mt-sDNA, further research is needed to explore its full potential in improving CRC screening adherence across different demographic groups.

Objective: To describe potential drug-drug interactions (DDIs) with oral advanced therapies among patients with ulcerative colitis (UC) and characterize clinical assessments before ozanimod initiation.

Methods: Adults with UC were selected from the Merative MarketScan Commercial Database (01 January 2018-31 January 2023); the index date was the most recent UC diagnosis. Patients had no other immune conditions in the 12-month baseline period before the index date. Those with moderate-to-severe UC were analyzed separately. Potential baseline DDIs were identified as claims for medications that may cause a moderate/severe DDI with Janus kinase (JAK) inhibitors (tofacitinib/upadacitinib) or ozanimod according to the Merative Micromedex Complete Drug Interactions Tool. Clinical assessments before ozanimod initiation were characterized.

Results: Of 58,870 patients with UC, 24,654 (41.9%) had moderate-to-severe UC. All potential DDIs with ozanimod were severe, while JAK inhibitors had moderate and severe potential DDIs. Among patients with UC, mean (standard deviation) number of severe DDIs was 2.0 (2.4) for ozanimod and 0.2 (0.5) for JAK inhibitors; in moderate-to-severe UC, it was 2.3 (2.6) for ozanimod and 0.4 (0.6) for JAK inhibitors. The most common potential DDIs for ozanimod in UC and moderate-to-severe UC were ondansetron (18.6% and 22.7%), azithromycin (11.9% and 12.8%), as well as hydrocodone, fentanyl, albuterol, ciprofloxacin, and metronidazole (9.0%-11.0% each). For JAK inhibitors, these were COVID-19 vaccines (30.7% and 31.4%), infliximab (8.5% and 20.2%), fluconazole (6.1% and 6.8%), and azathioprine (5.5% and 13.0%). Among patients initiating ozanimod, the first claim for a required clinical assessment was on average, 8 months before initiation.

Conclusion: Comorbidities and polypharmacy among patients with UC pose a high risk of DDIs for oral advanced therapies and required pre-treatment clinical assessments can be complicated. This justifies a thorough review of patient profiles for prescribers considering novel treatment options.

Objective: We describe discussions about the lung cancer treatment decision-making process across the patient journey from the perspective of patients and caregivers with diverse experiences of living with lung cancer.

Methods: Patient preference studies show individuals with lung cancer usually favor more aggressive treatments despite adverse events (AEs), in pursuit of better survival. However, patients are frequently passive in treatment decisions, suggesting there are barriers impairing patients' abilities to engage in shared decision-making. To explore this further, we asked patients with epidermal growth factor receptor-positive lung cancer and their caregivers to complete surveys and participate in focus group discussions facilitated by research specialists.

Results: US patients with lung cancer (n = 11) and caregivers (n = 4) took part in exploratory focus groups. While initial treatment decisions were mostly led by healthcare providers, participants became more engaged in their treatment over time. As in other studies, participants prioritized survival over AEs when selecting treatments and shared fears of being switched to less efficacious treatments or reduced dose if they disclosed AEs. Participants emphasized the importance of shared decision-making, early discussions about AEs, and access to patient advocates.

Conclusion: Healthcare providers should distribute reliable educational materials and have early conversations with patients on individual lung cancer treatment, health-related quality of life goals, potential AEs, and distinguishing AEs from disease progression symptoms.

Background: Sepsis remains a leading cause of mortality, especially among patients admitted to non-ICU settings like intermediate care units (IMCUs). Current prognostic tools have limitations in predicting outcomes in these patients. This study aimed to identify key predictors of mortality using decision tree analysis.

Methods: We conducted a prospective observational study from January 2023 to June 2024, enrolling 254 septic patients admitted to the IMCU of Santorso Hospital, Italy. Clinical, laboratory, and demographic data were collected, and decision tree analysis was performed to identify factors associated with 30-day mortality. Variables were compared using univariate and multivariate analyses, and significant predictors were incorporated into the decision tree model.

Results: The 30-day mortality rate was 14.6%. Serum albumin was identified as the root node of the decision tree, with lower levels (≤2.3 g/dL) strongly associated with mortality. Additional predictors were identified as higher NEWS scores (OR 1.153, p = 0.002) and older age (OR 1.062, p = 0.021). Traditional scoring systems like SOFA and APACHE did not significantly predict outcomes in this setting.

Conclusions: Serum albumin is a key prognostic marker in septic patients admitted to IMCUs, alongside NEWS and age. These findings suggest that albumin levels at admission may aid in early risk stratification and clinical decision-making in non-ICU environments. Future studies should validate these results across different healthcare settings to optimize sepsis management.