Nevin Manimala

BMJ Open. 2023 Aug 30;13(8):e072546. doi: 10.1136/bmjopen-2023-072546.

ABSTRACT

OBJECTIVES: Individuals under-recruited in diabetes research studies include those not seen at endocrinology centres and those from rural, low socioeconomic and/or under-represented racial/ethnic groups. The purpose of this descriptive analysis is to detail recruitment and retention efforts of Project ECHO Diabetes clinical sites affiliated with Stanford University and University of Florida.

DESIGN: Prospective collection of participant engagement and qualitative analysis of barriers and facilitators of research engagement within Project ECHO Diabetes, a virtual tele-education programme for healthcare providers in the management of individuals with insulin-requiring diabetes.

SETTING: Data were collected at the patient level, provider level and clinic level between 1 May 2021 and 31 July 2022.

PARTICIPANTS: Participants and study personnel were recruited from 33 Project ECHO Diabetes sites in California and Florida.

OUTCOMES: We report study completion rates for participants recruited into 33 Project ECHO Diabetes sites. Using barrier analysis, a methodology designed for the real-time assessment of interventions and system processes to identify barriers and facilitators, study personnel identified significant barriers to recruitment and retention and mapped them to actionable solutions.

RESULTS: In total, 872 participants (California n=495, Florida n=377) were recruited with differing recruitment rates by site (California=52.7%, Florida=21.5%). Barrier analysis identified lack of trust, unreliable contact information, communication issues and institutional review board (IRB) requirements as key recruitment barriers. Culturally congruent staff, community health centre (CHC) support, adequate funding and consent process flexibility were solutions to address recruitment challenges. Barriers to retention were inconsistent postal access, haemoglobin A1c kit collection challenges, COVID-19 pandemic and broadband/connectivity issues. Additional funding supporting research staff and analogue communication methods were identified as solutions address barriers to retention.

CONCLUSIONS: Funded partnerships with CHCs, trusted by their local communities, were key in our recruitment and retention strategies. IRB consent process flexibility reduced barriers to recruitment. Recruiting historically under-represented populations is feasible with funding aimed to address structural barriers to research participation.

PMID:37648378 | DOI:10.1136/bmjopen-2023-072546

JACC Cardiovasc Interv. 2023 Aug 28;16(16):1990-2000. doi: 10.1016/j.jcin.2023.05.030.

ABSTRACT

BACKGROUND: Computed tomography angiography (CTA) and invasive coronary angiography (ICA) are routinely performed before transcatheter aortic valve replacement (TAVR) to assess aortic root anatomy and screen for coronary artery disease (CAD), respectively.

OBJECTIVES: This study explored the efficacy of CTA as a screening tool for significant proximal CAD before TAVR.

METHODS: With proper ethical oversight, patients undergoing TAVR at Cleveland Clinic with a preprocedural CTA and invasive coronary angiography (ICA), and no prior percutaneous intervention, were identified from 2015 to 2021. Blinded to ICA results, the authors reviewed the left main, proximal left anterior descending coronary artery, proximal left circumflex coronary artery, and proximal right coronary artery by CTA coronary reconstruction to assess for nonsignificant stenosis (0% to 49%), moderate stenosis (50% to 69%), and severe stenosis (≥70%). Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and Cohen Kappa statistic were analyzed.

RESULTS: 2,217 patients (53.4% male, age 79.2 ± 8.5 years) met inclusion criteria. CTA evaluation revealed a sensitivity of 90%, specificity of 92%, PPV of 74%, and NPV of 97% for detecting ≥50% stenosis. Using a ≥70% stenosis cutoff, evaluation revealed a sensitivity of 91%, specificity of 97%, PPV of 83%, and NPV of 99%. Assessment of bypass graft patency revealed a sensitivity of 86%, specificity of 97%, PPV of 84%, and NPV of 98%. Cohen Kappa analysis indicated substantial to near perfect agreement between pre-TAVR CTA and ICA.

CONCLUSIONS: Pre-TAVR CTA has a high NPV for high-grade proximal stenosis of each coronary artery. As a result, CTA can be used as a screening tool to rule out significant proximal CAD in patients undergoing TAVR.

PMID:37648347 | DOI:10.1016/j.jcin.2023.05.030

Anticancer Res. 2023 Sep;43(9):3881-3889. doi: 10.21873/anticanres.16575.

ABSTRACT

Otorhinolaryngology tradition is that tonsillectomy (TE) is conducted among children and adolescents for obstructive sleep apnea secondary to adenotonsillar hypertrophy and in adults for chronic disease of the tonsils and adenoids (recurrent tonsillitis). Nevertheless, over the last 50 years, we have observed a decline in TE worldwide. As a result, there is an emerging concern of a correlated possible increased risk of tonsil cancer (TC) and other subtypes of oropharyngeal squamous cell carcinoma. Since the available data on such topics are limited and controversial, our aim was to elucidate the impact of TE on the incidence mainly of TC through a systematic review of the literature and a meta-analysis of the studies. After a thorough search, 7 retrospective studies were considered eligible for review and meta-analysis (MA). At MA, patients with a history of TE seem to show a reduced risk of TC but a higher predisposition for base of tongue (BOT) cancer (p<0.001): however, the elevated heterogeneity of the studies hampers drawing firm and convincing conclusions (statistical inconsistency >95%). In future, randomized control trials will be welcome to elucidate the prophylactic role of TE against TC and its real impact on BOT cancer.

PMID:37648322 | DOI:10.21873/anticanres.16575

Anticancer Res. 2023 Sep;43(9):4031-4036. doi: 10.21873/anticanres.16591.

ABSTRACT

BACKGROUND/AIM: Estrogen receptor (ER)-negative [ER(-)] invasive breast cancers (IBCs) are known to be more aggressive than their ER(+) counterparts. This is less well defined for ductal carcinoma in situ (DCIS). This study investigated the outcomes following the treatment of ER(-) DCIS.

PATIENTS AND METHODS: A total of 103 ER(-) DCIS patients diagnosed between 2004-2018 were retrospectively analyzed. Median follow-up was 63.9 months. Statistical analysis included descriptive statistics, non-parametric tests, T-test, logistic regression. The outcomes were compared to a group of 102 ER(+) DCIS patients from our institution.

RESULTS: Any breast event (BE) occurred in 10 (9.7%) patients at a median of 3.2 (1.7-7.2) years. The incidence of ipsilateral breast events (IBEs) was 5.8% (6/103). All IBE cases were ER(-) DCIS. All (n=4) contralateral breast events (CBEs) were ER(+) including 3 IBCs. Cumulative incidence of any BEs at 1, 2, and 5 years was 0%, 1.1%, and 9.1%, respectively. Among patients with ER(-) DCIS who developed BE, breast conserving surgery (BCS) had been performed for the initial DCIS in 90% of cases. In those without any BE, the BCS rate (vs. mastectomy) was 58.1% (p=0.08). Adjuvant radiotherapy after BCS was used less often among patients with vs. without subsequent BE (55.5% vs. 77.4%) (p=0.22). Predictors for BE occurrence were not identified. The incidence of any BE among patients with ER(+) DCIS was 6.9% and was not significantly different compared to ER(-) DCIS group (p=0.46).

CONCLUSION: ER(-) DCIS outcomes were similar to our institutional ER-positive DCIS group and the previously reported ones for predominantly ER-positive DCIS cohorts.

PMID:37648296 | DOI:10.21873/anticanres.16591

BMJ. 2023 Aug 30;382:e072348. doi: 10.1136/bmj-2022-072348.

ABSTRACT

OBJECTIVE: To systematically assess credibility and certainty of associations between cannabis, cannabinoids, and cannabis based medicines and human health, from observational studies and randomised controlled trials (RCTs).

DESIGN: Umbrella review.

DATA SOURCES: PubMed, PsychInfo, Embase, up to 9 February 2022.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Systematic reviews with meta-analyses of observational studies and RCTs that have reported on the efficacy and safety of cannabis, cannabinoids, or cannabis based medicines were included. Credibility was graded according to convincing, highly suggestive, suggestive, weak, or not significant (observational evidence), and by GRADE (Grading of Recommendations, Assessment, Development and Evaluations) (RCTs). Quality was assessed with AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews 2). Sensitivity analyses were conducted.

RESULTS: 101 meta-analyses were included (observational=50, RCTs=51) (AMSTAR 2 high 33, moderate 31, low 32, or critically low 5). From RCTs supported by high to moderate certainty, cannabis based medicines increased adverse events related to the central nervous system (equivalent odds ratio 2.84 (95% confidence interval 2.16 to 3.73)), psychological effects (3.07 (1.79 to 5.26)), and vision (3.00 (1.79 to 5.03)) in people with mixed conditions (GRADE=high), improved nausea/vomit, pain, spasticity, but increased psychiatric, gastrointestinal adverse events, and somnolence among others (GRADE=moderate). Cannabidiol improved 50% reduction of seizures (0.59 (0.38 to 0.92)) and seizure events (0.59 (0.36 to 0.96)) (GRADE=high), but increased pneumonia, gastrointestinal adverse events, and somnolence (GRADE=moderate). For chronic pain, cannabis based medicines or cannabinoids reduced pain by 30% (0.59 (0.37 to 0.93), GRADE=high), across different conditions (n=7), but increased psychological distress. For epilepsy, cannabidiol increased risk of diarrhoea (2.25 (1.33 to 3.81)), had no effect on sleep disruption (GRADE=high), reduced seizures across different populations and measures (n=7), improved global impression (n=2), quality of life, and increased risk of somnolence (GRADE=moderate). In the general population, cannabis worsened positive psychotic symptoms (5.21 (3.36 to 8.01)) and total psychiatric symptoms (7.49 (5.31 to 10.42)) (GRADE=high), negative psychotic symptoms, and cognition (n=11) (GRADE=moderate). In healthy people, cannabinoids improved pain threshold (0.74 (0.59 to 0.91)), unpleasantness (0.60 (0.41 to 0.88)) (GRADE=high). For inflammatory bowel disease, cannabinoids improved quality of life (0.34 (0.22 to 0.53) (GRADE=high). For multiple sclerosis, cannabinoids improved spasticity, pain, but increased risk of dizziness, dry mouth, nausea, somnolence (GRADE=moderate). For cancer, cannabinoids improved sleep disruption, but had gastrointestinal adverse events (n=2) (GRADE=moderate). Cannabis based medicines, cannabis, and cannabinoids resulted in poor tolerability across various conditions (GRADE=moderate). Evidence was convincing from observational studies (main and sensitivity analyses) in pregnant women, small for gestational age (1.61 (1.41 to 1.83)), low birth weight (1.43 (1.27 to 1.62)); in drivers, car crash (1.27 (1.21 to 1.34)); and in the general population, psychosis (1.71 (1.47 to 2.00)). Harmful effects were noted for additional neonatal outcomes, outcomes related to car crash, outcomes in the general population including psychotic symptoms, suicide attempt, depression, and mania, and impaired cognition in healthy cannabis users (all suggestive to highly suggestive).

CONCLUSIONS: Convincing or converging evidence supports avoidance of cannabis during adolescence and early adulthood, in people prone to or with mental health disorders, in pregnancy and before and while driving. Cannabidiol is effective in people with epilepsy. Cannabis based medicines are effective in people with multiple sclerosis, chronic pain, inflammatory bowel disease, and in palliative medicine but not without adverse events.

STUDY REGISTRATION: PROSPERO CRD42018093045.

FUNDING: None.

PMID:37648266 | DOI:10.1136/bmj-2022-072348

J Immunother Cancer. 2023 Aug;11(8):e007118. doi: 10.1136/jitc-2023-007118.

ABSTRACT

BACKGROUND: Brexucabtagene autoleucel (brexu-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved in the USA for adults with relapsed or refractory (R/R) B-cell acute lymphoblastic leukemia (B-ALL) and in the European Union for patients ≥26 years with R/R B-ALL. After 2 years of follow-up in ZUMA-3, the overall complete remission (CR) rate (CR+CR with incomplete hematological recovery (CRi)) was 73%, and the median overall survival (OS) was 25.4 months in 78 Phase 1 and 2 patients with R/R B-ALL who received the pivotal dose of brexu-cel. Outcomes by prior therapies and subsequent allogeneic stem cell transplantation (alloSCT) are reported.

METHODS: Eligible adults had R/R B-ALL and received one infusion of brexu-cel (1×10⁶ CAR T cells/kg) following conditioning chemotherapy. The primary endpoint was the CR/CRi rate per central review. Post hoc subgroup analyses were exploratory with descriptive statistics provided.

RESULTS: Phase 1 and 2 patients (N=78) were included with median follow-up of 29.7 months (range, 20.7-58.3). High CR/CRi rates were observed across all prior therapy subgroups examined: 1 prior line of therapy (87%, n=15) and ≥2 prior lines (70%, n=63); prior blinatumomab (63%, n=38) and no prior blinatumomab (83%, n=40); prior inotuzumab (59%, n=17) and no prior inotuzumab (77%, n=61); and prior alloSCT (76%, n=29) and no prior alloSCT (71%, n=49). The frequency of Grade ≥3 cytokine release syndrome, neurological events, and treatment-related Grade 5 adverse events were largely similar among prior therapy subgroups.Median duration of remission (DOR) in responders with (n=14) and without (n=43) subsequent alloSCT was 44.2 (95% CI, 8.1 to not estimable (NE)) and 18.6 months (95% CI, 9.4 to NE); median OS was 47.0 months (95% CI, 10.2 to NE) and not reached (95% CI, 23.2 to NE), respectively. Median DOR and OS were not reached in responders without prior or subsequent alloSCT (n=22).

CONCLUSIONS: In ZUMA-3, adults with R/R B-ALL benefited from brexu-cel, regardless of prior therapies and subsequent alloSCT status, though survival appeared better in patients without certain prior therapies and in earlier lines of therapy. Additional studies are needed to determine the impact prior therapies and subsequent alloSCT have on outcomes of patients who receive brexu-cel.

PMID:37648261 | DOI:10.1136/jitc-2023-007118

Am Surg. 2023 Aug 30:31348231199174. doi: 10.1177/00031348231199174. Online ahead of print.

ABSTRACT

AIM: In this study, it was aimed to evaluate the characteristic features and survival of secretory carcinoma of the breast (SCB), which is one of the rare malignant tumors of the breast.

METHODS: Data of patients with histopathological diagnosis of SCB between 2010 and 2019 were extracted from the SEER database. These patients were evaluated in terms of age, race, molecular subtype, grade, estrogen receptor (ER), progesterone receptor (PR), HER2 receptor, TNM stage, surgical status, chemotherapy and radiotherapy treatment. Overall survival (OS) and breast cancer-specific survival (BCSS) of the whole population and subgroups [in terms of surgery procedure (mastectomy/breast-conserving surgery), and hormone receptor status (positive/negative)] were analyzed.

RESULTS: 70 patients were included in the study. The mean age was 57 years (range 2-82). 32.9% of the patients were diagnosed under the age of 50. 97.1% of the patients were female; 2.9% were male. The vast majority of patients were white race (81.4%). Although the rates of localization were higher in the upper outer quadrant (31.4%), centrally located tumors (18.5%) were also quite common. The most frequently detected molecular subtype was hormone positive/HER2 negative. All patients were non-metastatic, 81.4% of patients did not have lymph node metastases, and most of the patients were stage IA. Median follow-up was 37 months (range 0-118 months). Considering all patients, OS was 76.3%, 5-year OS was 91.8%, and BCSS was 88%, 5-year BCSS was 97.8%. There was no statistically significant difference in OS and BCSS according to subgroups (P > .01).

CONCLUSION: SCB, a rare histopathologic type, has high OS and BCSS rates.

PMID:37648259 | DOI:10.1177/00031348231199174

BJGP Open. 2023 Aug 30:BJGPO.2023.0084. doi: 10.3399/BJGPO.2023.0084. Online ahead of print.

ABSTRACT

BACKGROUND: Lifetime risk of fragility fractures is 50% in post-menopausal women and 20% in men aged over 50 years. Identifying people at high risk facilitates early intervention and reduction of biopsychosocial morbidity associated with these fractures.

AIM: To explore if bone health assessment (BHA) rates differ between women and men aged 50 years and over with fragility fracture risk factors.

DESIGN & SETTING: A primary care-based cohort study METHOD: Patients were identified from the Consultations in Primary Care Archive (CiPCA) database between 2002 and 2014 with one or more fragility fracture risk factors (previous fractures, falls and prolonged steroid use). Evaluation of BHA within twelve months of presentation of the first risk factor was carried out by searching for codes for fracture risk assessment tools (FRAX/QFracture), bone density measurement, specialist service referral or if bone-protection medication was started.

RESULTS: 15,581 patients with risk factors were identified; men represented 40% of the cohort. 1,172 (7.5%) had BHA performed within one year of presentation. 8.9% of females and 5.5% of males had BHAs, which was found with strong statistical evidence (X ²=59.88, P=1 × 10^-14). This relationship prevailed after adjusting for other covariates such as co-morbidity and number of consultations with an odds ratio of 1.25 (95% Confidence Interval 1.08-1.43).

CONCLUSION: This study shows that rates of BHA were generally low and even lower in men. Primary care clinicians should be alert to fragility fracture risk factors in both men and women to enable early assessment and intervention.

PMID:37648258 | DOI:10.3399/BJGPO.2023.0084

Respirology. 2023 Aug 30. doi: 10.1111/resp.14588. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVE: The relative effectiveness of initial non-invasive respiratory strategies for acute respiratory failure using continuous positive airway pressure (CPAP) or high-flow nasal cannula (HFNC) is unclear.

METHODS: We conducted a multicenter, open-label, parallel-group randomized controlled trial to compare the efficacy of CPAP and HFNC on reducing the risk of meeting the prespecified criteria for intubation and improving clinical outcomes of acute hypoxemic respiratory failure. The primary endpoint was the time taken to meet the prespecified criteria for intubation within 28 days.

RESULTS: Eighty-five patients were randomly assigned to the CPAP or HFNC group. Eleven (28.9%) in the CPAP group and twenty (42.6%) in the HFNC group met the criteria for intubation within 28 days. Compared with HFNC, CPAP reduced the risk of meeting the intubation criteria (hazard ratio [HR], 0.327; 95% CI, 0.148-0.724; p = 0.006). There were no significant between-group differences in the intubation rates, in-hospital and 28-day mortality rates, ventilator-free days, duration of the need for respiratory support, or duration of hospitalization for respiratory illness. Pulmonary oxygenation was significantly better in the CPAP group, with significantly lower pH and higher partial pressure of carbon dioxide, but there were no differences in the respiratory rate between groups. CPAP and HFNC were associated with few possibly causal adverse events.

CONCLUSION: CPAP is more effective than HFNC at reducing the risk of meeting the intubation criteria in patients with acute hypoxemic respiratory failure.

PMID:37648252 | DOI:10.1111/resp.14588

Oncologist. 2023 Aug 30:oyad223. doi: 10.1093/oncolo/oyad223. Online ahead of print.

ABSTRACT

BACKGROUND: Adjuvant therapies have been approved for resected melanoma based on improved recurrence-free survival. We present early findings from a real-world study on adjuvant treatments for melanoma.

METHODS: A comprehensive chart review was conducted for patients receiving adjuvant systemic therapy for resected high-risk stages III and IV melanoma. Statistical analysis was performed to assess recurrence-free survival and subgroup differences.

RESULTS: A total of 149 patients (median age = 58.0 years, 61.1% men, 49.7% with BRAF V600E/K genotypes) were included, with 94.6% having resected stage III melanoma. Anti-PD-1 immunotherapy was received by 86.5% of patients, while 13.4% received BRAF-targeted therapy. At a median follow-up of 22.4 months, the recurrence rate was 31.5%, with 1-year and 2-year recurrence-free survival rates of 79% and 62%, respectively. Similar recurrence rates were observed between anti-PD-1 immunotherapy and BRAF-targeted therapy. Long-term toxicity affected 27.4% of patients, with endocrinopathies and late-emergent immune-related adverse events being common.

CONCLUSIONS: Real-world adjuvant systemic therapy aligns with clinical trial practice. Recurrence rates remain high despite treatment, and long-term toxicities, including endocrinopathies and chronic inflammatory conditions, are not uncommon.

PMID:37648247 | DOI:10.1093/oncolo/oyad223