Tag: pubmed

BMJ Open Qual. 2021 Sep;10(3):e001063. doi: 10.1136/bmjoq-2020-001063.

ABSTRACT

BACKGROUND: Miscommunication during clinical handover can lead to partial information transfer and healthcare provider dissatisfaction. We hypothesised that a quality improvement project to standardise the cardiovascular intensive care unit (CVICU) handover could improve healthcare provider satisfaction and reduce information omission.

METHODS: After institutional review board approval, the operating room (OR) to CVICU handover was audited prior, post and 1 year after standardisation implementation. The medical information transferred, healthcare provider participation and satisfaction, and patient outcome data were collected. Additionally, surveys were sent to the OR and CVICU staff by email.

RESULTS: There were 68 handover processes observed. The odds of greater satisfaction with handover for providers were 18 times higher with the process post implementation (p<0.0001) and 26 times higher 1 year after implementation (p<0.0001). There was statistically significant difference between intensive care unit resident presence (45% vs 76% vs 91%, p=0.004), surgical faculty presence (10% vs 36% vs 45%, p=0.034) and surgical fellow presence (15% vs 64% vs 62%, p=0.001) between the three time periods. More information related to the surgeon (5% vs 52% vs 27%, p=0.002), the medical history (65% vs 96% vs 91%, p=0.014) and the cardiopulmonary bypass (47% vs 88% vs 76%, p=0.017) was conveyed. The duration of mechanical ventilation was shorter after implementation (2.2±2.6 days vs 1.2±1.9 days vs 0.5±1.2 days, p=0.026).

CONCLUSIONS: One year after the OR to CVICU standardised handover implementation, the healthcare provider satisfaction remained increased, more team members participated and the information transfer increased. Although some clinical outcomes improved, further studies are recommended to prove causality.

PMID:34518301 | DOI:10.1136/bmjoq-2020-001063

Clin Cancer Res. 2021 Sep 13:clincanres.4185.2020. doi: 10.1158/1078-0432.CCR-20-4185. Online ahead of print.

ABSTRACT

PURPOSE: MPS1 kinase inhibitor, BAY 1217389 (BAY) synergizes with paclitaxel. This phase 1 study assessed the combination of BAY with paclitaxel using a novel randomized continuous reassessment method (rCRM) to improve dose determination.

EXPERIMENTAL DESIGN: Patients with solid tumors were randomized to receive oral BAY (BID 2‑days‑on/5‑days‑off) with weekly paclitaxel (90 mg/m²) or paclitaxel monotherapy in cycle 1. Dose escalation was guided by CRM modeling. Primary objectives were to assess safety, establish the maximum tolerated dose (MTD) of BAY and to evaluate the pharmacokinetic profiles for both compounds. Simulations were performed to determine the contribution of the rCRM for dose determination.

RESULTS: In total, 75 patients were enrolled. The main dose limiting toxicities were hematologic toxicities (55.6%). The MTD of BAY was established at 64 mg BID with paclitaxel. Inclusion of a control arm enabled the definitive attribution of grade {greater than or equal to}3 neutropenia to higher BAY exposure (AUC_0-12 (P< .001)). After determining the MTD, we included nineteen breast cancer patients at this dose for dose expansion. Other common toxicities were nausea (45.3%), fatigue (41.3%) and diarrhea (40.0%). Overall confirmed responses were seen in 31.6% of evaluable patients. Simulations showed that rCRM outperforms traditional designs in determining the true MTD.

CONCLUSIONS: The combination of BAY with paclitaxel was associated with considerable toxicity without a therapeutic window. However, the use of the rCRM design enabled us to determine the exposure-toxicity relation for BAY. Therefore we propose that the rCRM could improve dose determination in phase I trials that combine agents with overlapping toxicities.

PMID:34518310 | DOI:10.1158/1078-0432.CCR-20-4185

J Am Soc Nephrol. 2021 Sep 13:ASN.2021030382. doi: 10.1681/ASN.2021030382. Online ahead of print.

ABSTRACT

Background Up to 70% of patients with ANCA-associated vasculitis (AAV) develop glomerulonephritis, with 26% progressing to ESKD. Diagnostic-grade and noninvasive tools to detect active renal inflammation are needed. Urinary soluble CD163 (sCD163) is a promising biomarker of active renal vasculitis, but a diagnostic-grade assay, assessment of its utility in prospective diagnosis of renal vasculitis flares, and evaluation of its utility in proteinuric states are needed. Methods We assessed a diagnostic-grade urinary sCD163 assay in (1) a real-world cohort of 405 patients with AAV and 121 healthy and 488 non-AAV disease controls; (2) a prospective multicenter study of 84 patients with potential renal vasculitis flare; (3) a longitudinal multicenter cohort of 65 patients with podocytopathy; and (4) a cohort of 29 patients with AAV (with or without proteinuria) and 10 controls. Results We established a diagnostic reference range, with a cutoff of 250 ng/mmol for active renal vasculitis (area under the curve [AUC], 0.978). Using this cutoff, urinary sCD163 was elevated in renal vasculitis flare (AUC, 0.95) but remained low in flare mimics, such as nonvasculitic acute kidney injury. Urinary sCD163’s specificity declined in AAV patients with nephrotic-range proteinuria and in primary podocytopathy, with 62% of nephrotic patients displaying a “positive” urinary sCD163. In AAV patients with significant proteinuria, urinary sCD163 normalization to total urine protein rather than creatinine provided the greatest clinical utility for diagnosing active renal vasculitis. Conclusions Urinary sCD163 is elevated in renal vasculitis flare and remains low in flare mimics. Nonspecific protein leakage in nephrotic syndrome elevates urinary sCD163 in the absence of glomerular macrophage infiltration, resulting in false-positive results; this can be corrected with urine protein normalization.

PMID:34518279 | DOI:10.1681/ASN.2021030382

J Immunother Cancer. 2021 Sep;9(9):e003281. doi: 10.1136/jitc-2021-003281.

ABSTRACT

The combination of ipilimumab plus nivolumab (I+N) has greatly improved outcomes in patients with intermediate or poor-risk untreated metastatic renal cell carcinoma (mRCC). However, little is known about the outcomes of patients with brain metastasis (BrM) treated with I+N. A search was performed to retrospectively identify all patients with mRCC treated with I+N in the Duke Cancer Institute and the Cleveland Clinic Taussig Cancer Center, followed by a chart review. Patients were included if they had BrM at the time of I+N initiation. Cohort characteristics are summarized with descriptive statistics. Kaplan-Meier method was used to estimate overall survival (OS) and global, intracranial, and extracranial progression-free survival (PFS) for the cohort and log rank test was used to compare OS and PFS between patient groups. Radiographic response was categorized by RECIST. Fisher’s exact test was used to correlate patient factors with radiographic response. From October 2017 to December 2020, 19 patients with BrM received I+N for mRCC with a median follow-up time of 27.1 months (range 15.0-35.6). By International Metastatic RCC Database Consortium (IMDC) risk criteria, 16% had favorable, 58% had intermediate, and 26% had poor-risk disease. 68% were systemic therapy naïve, and 77% of patients had clear cell histology. 95% had received local CNS directed therapy with surgery, radiotherapy, or both. The objective response rate was 44% (0% complete response) with three of six patients treated in the second line or greater setting experiencing a partial response. The median PFS was 7.6 months (95% CI 5.6 to 14.9). The median extracranial PFS was 8.5 months (95% CI 5.6 to 19.7), and median intracranial PFS was 14.7 months (95% CI 7.2 to not reached). No variables assessed were significantly associated with radiographic response (gender, IMDC risk, presence of bone metastasis, line of therapy, or presence of immune related adverse events). In our retrospective cohort of patients with mRCC with BrM, I+N, in combination with CNS-directed local therapy, appears to have clinical efficacy as previously described with responses seen beyond the first-line setting. Further investigation is warranted in this population given exclusion from prior clinical trials.

PMID:34518292 | DOI:10.1136/jitc-2021-003281

BMJ Open. 2021 Sep 13;11(9):e049938. doi: 10.1136/bmjopen-2021-049938.

ABSTRACT

OBJECTIVES: To investigate (1) self-reported societal comprehension of common and usually non-serious terms found in lumbar spine imaging reports and (2) its relationship to perceived seriousness, likely persistence of low back pain (LBP), fear of movement, back beliefs and history and intensity of LBP.

DESIGN: Cross-sectional online survey of the general public.

SETTING: Five English-speaking countries: UK, USA, Canada, New Zealand and Australia.

PARTICIPANTS: Adults (age >18 years) with or without a history of LBP recruited in April 2019 with quotas for country, age and gender.

PRIMARY AND SECONDARY OUTCOME MEASURES: Self-reported understanding of 14 terms (annular fissure, disc bulge, disc degeneration, disc extrusion, disc height loss, disc protrusion, disc signal loss, facet joint degeneration, high intensity zone, mild canal stenosis, Modic changes, nerve root contact, spondylolisthesis and spondylosis) commonly found in lumbar spine imaging reports. For each term, we also elicited worry about its seriousness, and whether its presence would indicate pain persistence and prompt fear of movement.

RESULTS: From 774 responses, we included 677 (87.5%) with complete and valid responses. 577 (85%) participants had a current or past history of LBP of whom 251 (44%) had received lumbar spine imaging. Self-reported understanding of all terms was poor. At best, 235 (35%) reported understanding the term ‘disc degeneration’, while only 71 (10.5%) reported understanding the term ‘Modic changes’. For all terms, a moderate to large proportion of participants (range 59%-71%), considered they indicated a serious back problem, that pain might persist (range 52%-71%) and they would be fearful of movement (range 42%-57%).

CONCLUSION: Common and usually non-serious terms in lumbar spine imaging reports are poorly understood by the general population and may contribute to the burden of LBP.

TRIAL REGISTRATION NUMBER: ACTRN12619000545167.

PMID:34518265 | DOI:10.1136/bmjopen-2021-049938

BMJ Open. 2021 Sep 13;11(9):e052339. doi: 10.1136/bmjopen-2021-052339.

ABSTRACT

INTRODUCTION: Improving the mental health of young people is a global public health priority. In Latin America, young people living in deprived urban areas face various risk factors for mental distress. However, most either do not develop mental distress in the form of depression and anxiety, or recover within a year without treatment from mental health services. This research programme seeks to identify the personal and social resources that help young people to prevent and recover from mental distress.

METHODS AND ANALYSIS: A cross-sectional study will compare personal and social resources used by 1020 young people (aged 15-16 and 20-24 years) with symptoms of depression and/or anxiety and 1020 without. A longitudinal cohort study will follow-up young people with mental distress after 6 months and 1 year and compare resource use in those who do and do not recover. An experience sampling method study will intensively assess activities, experiences and mental distress in subgroups over short time periods. Finally, we will develop case studies highlighting existing initiatives that effectively support young people to prevent and recover from mental distress. The analysis will assess differences between young people with and without distress at baseline using t-tests and χ² tests. Within the groups with mental distress, multivariate logistic regression analyses using a random effects model will assess the relationship between predictor variables and recovery.

ETHICS AND DISSEMINATION: Ethics approvals are received from Ethics Committee in Biomedical Research, Faculty of Medicine, University of Buenos Aires; Faculty of Medicine-Research and Ethics Committee of the Pontificia Universidad Javeriana, Bogotá; Institutional Ethics Committee of Research of the Universidad Peruana Cayetano Heredia and Queen Mary Ethics of Research Committee. Dissemination will include arts-based methods and target different audiences such as national stakeholders, researchers from different disciplines and the general public.

TRIAL REGISTRATION NUMBER: ISRCTN72241383.

PMID:34518275 | DOI:10.1136/bmjopen-2021-052339

BMJ Open. 2021 Sep 13;11(9):e049476. doi: 10.1136/bmjopen-2021-049476.

ABSTRACT

OBJECTIVES: To describe the prevalence of comorbidities in a population referred to standardised first-line intervention (patient education and exercise) for hip and knee osteoarthritis (OA), in comparison with the general population. Furthermore, we aimed to evaluate if eventual differences were associated with socioeconomic inequalities.

DESIGN: Register-based study.

SETTING: Primary healthcare, Sweden.

PARTICIPANTS: Individuals with hip and/or knee OA included in the Better Management for Patients with Osteoarthritis Register between 2008 and 2016 and and an age-matched, sex-matched and residence-matched reference cohort (1:3) from the general Swedish population.

OUTCOME MEASURES: Comorbidities were identified with the RxRisk Index, the Elixhauser Comorbidity Index and the Charlson Comorbidity Index, and presented with descriptive statistics as (1) individual diseases, (2) disease categories and (3) scores for each index. The prevalence of comorbidities in the two populations was tested using logistic regression, with separate analyses for age groups and the most affected joint. We then adjusted the analyses for socioeconomic status.

RESULTS: In this OA population, 85% had ≥1 comorbidity compared with 78% of the reference cohort (OR; 1.62 (95% CI 1.59 to 1.66)). Cardiovascular/blood diseases were the most common comorbidities in both populations (OA, 59%; reference, 54%), with OR; 1.22 (95% CI 1.20 to 1.24) for the OA population. Younger individuals with OA were more comorbid than their matched references overall, and population differences decreased with age (eg, ≥3 comorbidities, aged ≤45 years OR; 1.74 (95% CI 1.52 to 1.98), ≥81 years OR; 0.95 (95% CI 0.87 to 1.04)). Individuals with knee OA were more comorbid than those with hip OA overall. Adjustment for socioeconomic status did not change the estimates.

CONCLUSION: Comorbidities were more common among individuals with hip and knee OA than among matched references from the general population. The differences could not be explained by socioeconomic status.

TRIAL REGISTRATION NUMBER: NCT03438630.

PMID:34518262 | DOI:10.1136/bmjopen-2021-049476

BMJ Open. 2021 Sep 13;11(9):e047141. doi: 10.1136/bmjopen-2020-047141.

ABSTRACT

INTRODUCTION: Apnoea affects 85% of premature infants under 34 weeks of age and would be an important risk factor for subsequent neuropsychological disorders. Currently, premature children with life-threatening apnoeas receive stimulants such as methylxanthines (mainly, caffeine) or doxapram (an analeptic unlicensed in children under 15). However, these products have undesirable effects (hyperarousal, irritability, sleep disorders, tachycardia) and are not always effective because apnoea does persist in some premature newborns. Previous studies have indicated that odorant stimulation, a non-invasive intervention, may stimulate the respiratory rhythm. The objective of the present protocol is to reduce the occurrence of apnoeic episodes in premature newborns by controlled odorant stimulation added to current pharmacological treatments.

METHODS AND ANALYSIS: The project is a randomised open-label Latin-square trial with independent evaluation of the main endpoint. It will include 60 preterm neonates from two university hospital neonatal intensive care units over 2 years (2021-2023). Each newborn will receive no (S0), sham (S1) or real olfactory stimulation (S2) in random order. During S2, three distinct odorants (mint, grapefruit and vanilla) will be delivered successively, in puffs, over 24 hours. Mint and grapefruit odours stimulate the main and the trigeminal olfactory pathways, whereas vanilla odour stimulates only the main olfactory pathway. A statistical analysis will compare the incidence of apnoeic episodes during S1 versus S2 using a mixed effects Poisson model.

ETHICS AND DISSEMINATION: Ethical approval was obtained from the Comité de Protection des Personnes Île-de-France XI (# 2017-AO13-50-53). The results will be disseminated through various scientific meetings, specialised peer-reviewed journals and, whenever possible, posted on appropriate public websites.

TRIAL REGISTRATION NUMBER: NCT02851979; Pre-results.

PMID:34518252 | DOI:10.1136/bmjopen-2020-047141

BMJ Open. 2021 Sep 13;11(9):e048215. doi: 10.1136/bmjopen-2020-048215.

ABSTRACT

INTRODUCTION: In Aotearoa New Zealand, Māori and Pacific people experience worse health outcomes compared with other New Zealanders. No population-based eye health survey has been conducted, and eye health services do not generate routine monitoring reports, so the extent of eye health inequality is unknown. This information is required to plan equitable eye health services. Here we outline the protocol for a scoping review to report the nature and extent of the evidence reporting vision impairment, and the use of eye health services by ethnicity in New Zealand.

METHODS AND ANALYSIS: An information specialist will conduct searches on MEDLINE and Embase, with no limit on publication dates or language. We will search the grey literature via websites of relevant government and service provider agencies. Reference lists of included articles will be screened. Observational studies will be included if they report the prevalence of vision impairment, or any of the main causes (cataract, uncorrected refractive error, macular degeneration, glaucoma or diabetic retinopathy) or report the use of eye health services in New Zealand among people of any age. Two authors will independently review titles, abstracts and full-text articles, and complete data extraction. Overall findings will be summarised using descriptive statistics and thematic analysis, with an emphasis on disaggregation by ethnicity where this information is available.

ETHICS AND DISSEMINATION: Ethical approval has not been sought as our review will only include published and publicly accessible data. We will publish the review in an open access peer-reviewed journal. We anticipate the findings will be useful to organisations and providers in New Zealand responsible to plan and deliver eye care services, as well as stakeholders in other countries with differential access to eye care.

REGISTRATION DETAILS: The protocol has been registered with Open Science Framework (https://osf.io/yw7xb).

PMID:34518256 | DOI:10.1136/bmjopen-2020-048215

BMJ Open. 2021 Sep 13;11(9):e048550. doi: 10.1136/bmjopen-2020-048550.

ABSTRACT

OBJECTIVES: Medicine is facing a physician-scientist shortage. By offering extracurricular research programmes (ERPs), the physician-scientist training pipeline could already start in undergraduate phases of medical training. However, previous studies into the effects of ERPs are mainly retrospective and lack baseline measurements and control groups. Therefore, the current study mimics a randomised controlled trial to examine the effects of an ERP.

DESIGN: Prospective cohort study with baseline measurement and comparable control group.

SETTING: One cohort of 315 medical undergraduates in one Dutch University Medical Center are surveyed yearly. To examine the effects of the ERP on academic achievement and motivational factors, regression analyses were used to compare ERP students to students showing ERP-interest only, adjusted for relevant baseline scores.

PARTICIPANTS: Out of the 315 students of the whole cohort, 56 participated within the ERP and are thus included. These ERP students are compared with 38 students showing ERP-interest only (ie, control group).

PRIMARY OUTCOME MEASURE: Academic achievement after 2 years (ie, in-time bachelor completion, bachelor grade point average (GPA)) and motivational factors after 18 months (ie, intrinsic motivation for research, research self-efficacy, perceptions of research, curiosity).

RESULTS: ERP participation is related to a higher odds of obtaining a bachelor degree in the appointed amount of time (adjusted OR=2.95, 95% CI 0.83 to 10.52). Furthermore, starting the ERP resulted in higher levels of intrinsic motivation for research, also after adjusting for gender, age, first-year GPA and motivational baseline scores (β=0.33, 95% CI 0.04 to 0.63). No effect was found on research self-efficacy beliefs, perceptions of research and curiosity.

CONCLUSIONS: Previous research suggested that intrinsic motivation is related to short-term and long-term research engagement. As our findings indicate that starting the ERP is related to increased levels of intrinsic motivation for research, ERPs for undergraduates could be seen as an important first step in the physician-scientist pipeline.

PMID:34518257 | DOI:10.1136/bmjopen-2020-048550