Nevin Manimala

BMJ Open. 2021 Nov 29;11(11):e047836. doi: 10.1136/bmjopen-2020-047836.

ABSTRACT

BACKGROUND: ‘Weekend effect’ is a term used to describe the increased mortality associated with weekend emergency admissions to hospital, in contrast with admission on weekdays. The objective of the present study is to determine whether the weekend effect is present in hospitals in Catalonia.

METHODS: We analysed all urgent admissions in Catalonia in 2018, for a group of pathologies. Two groups were defined (those admitted on a weekday and those admitted on a weekend). We obtained mortality at 3, 7, 15 and 30 days, and applied a proportions test to both groups. Additionally, we used Cox’s regression for mortality at 30 days, using the admission on a weekend as the exposition, adjusting by socioeconomic and clinical variables. We used the hospital discharge database and the Central Registry of the Insured Population.

RESULTS: 72 427 admissions for the selected pathologies during 2018 were found. No statistically significant differences in mortality at 30 days (p=0.524) or at 15 days (p=0.119) according to the day of admission were observed. However, significant differences were found in mortality at 7 days (p=0.025) and at 3 days (p=0.002). The hazard rate associated with the weekend was 1.13 (95% CI: 1.04 to 1.23). By contrast, the adjusted HR of the weekend interaction with time was 0.99 (95% CI: 0.99 to 1.00).

CONCLUSIONS: There is a weekend effect, but it is not constant in time. This could suggest the existence of dysfunctions in the quality of care during the weekend.

PMID:34845065 | DOI:10.1136/bmjopen-2020-047836

Proc Natl Acad Sci U S A. 2021 Dec 7;118(49):e2116427118. doi: 10.1073/pnas.2116427118.

ABSTRACT

Acute myeloid leukemia (AML) patients rarely have long first remissions (LFRs; >5 y) after standard-of-care chemotherapy, unless classified as favorable risk at presentation. Identification of the mechanisms responsible for long vs. more typical, standard remissions may help to define prognostic determinants for chemotherapy responses. Using exome sequencing, RNA-sequencing, and functional immunologic studies, we characterized 28 normal karyotype (NK)-AML patients with >5 y first remissions after chemotherapy (LFRs) and compared them to a well-matched group of 31 NK-AML patients who relapsed within 2 y (standard first remissions [SFRs]). Our combined analyses indicated that genetic-risk profiling at presentation (as defined by European LeukemiaNet [ELN] 2017 criteria) was not sufficient to explain the outcomes of many SFR cases. Single-cell RNA-sequencing studies of 15 AML samples showed that SFR AML cells differentially expressed many genes associated with immune suppression. The bone marrow of SFR cases had significantly fewer CD4⁺ Th1 cells; these T cells expressed an exhaustion signature and were resistant to activation by T cell receptor stimulation in the presence of autologous AML cells. T cell activation could be restored by removing the AML cells or blocking the inhibitory major histocompatibility complex class II receptor, LAG3. Most LFR cases did not display these features, suggesting that their AML cells were not as immunosuppressive. These findings were confirmed and extended in an independent set of 50 AML cases representing all ELN 2017 risk groups. AML cell-mediated suppression of CD4⁺ T cell activation at presentation is strongly associated with unfavorable outcomes in AML patients treated with standard chemotherapy.

PMID:34845035 | DOI:10.1073/pnas.2116427118

Clin Cancer Res. 2021 Nov 29:clincanres.3131.2021. doi: 10.1158/1078-0432.CCR-21-3131. Online ahead of print.

ABSTRACT

PURPOSE: Metastatic hormone receptor-positive (HR-positive), HER2-negative breast cancer is an important cause of cancer mortality. Endocrine treatment with or without additional targeted therapies has been the mainstay of treatment. This trial was designed to evaluate the combination of fulvestrant plus everolimus versus fulvestrant, everolimus and anastrozole compared to fulvestrant alone in the first-line treatment of advanced HR-positive, HER2-negative breast cancer.

EXPERIMENTAL DESIGN: This randomized placebo-controlled trial included postmenopausal women with HR-positive, HER2-negative advanced breast cancer who had received no prior systemic therapy for metastatic disease. Participants were randomized to one of three treatment arms and the primary outcome was progression-free survival (PFS), comparing combinations of fulvestrant and everolimus with or without anastrozole to fulvestrant alone. Circulating tumor cells (CTC), as measured with two different methods, and circulating tumor DNA (ctDNA) were evaluated serially prior to treatment and the beginning of the second cycle of therapy.

RESULTS: Due in part to changes in clinical practice, the study was closed after accruing only 37 participants. There was no evidence that everolimus-containing combination treatment improved PFS or overall survival relative to fulvestrant alone. When modeled continuously, an association was observed of baseline CTC and ctDNA with poorer survival.

CONCLUSION: Although power of the study was limited, the findings were unable to support the routine use of everolimus combination endocrine therapy in the first-line treatment of advanced hormone-sensitive breast cancer. Prognostic impact of baseline ctDNA and copy number variations in CTC was demonstrated.

PMID:34844978 | DOI:10.1158/1078-0432.CCR-21-3131

CMAJ. 2021 Nov 29;193(47):E1798-E1806. doi: 10.1503/cmaj.210659.

ABSTRACT

BACKGROUND: The COVID-19 pandemic has had a major impact on access to health care resources. Our objective was to estimate the impact of the COVID-19 pandemic on the incidence of childhood cancer in Canada. We also aimed to compare the proportion of patients who enrolled in clinical trials at diagnosis, presented with metastatic disease or had an early death during the first 9 months of the COVID-19 pandemic compared with previous years.

METHODS: We conducted an observational study that included children younger than 15 years with a new diagnosis of cancer between March 2016 and November 2020 at 1 of 17 Canadian pediatric oncology centres. Our primary outcome was the monthly age-standardized incidence rates (ASIRs) of cancers. We evaluated level and trend changes using interventional autoregressive integrated moving average models. Secondary outcomes were the proportion of patients who were enrolled in a clinical trial, who had metastatic or advanced disease and who died within 30 days. We compared the baseline and pandemic periods using rate ratios (RRs) and 95% confidence intervals (CIs).

RESULTS: Age-standardized incidence rates during COVID-19 quarters were 157.7, 164.6, and 148.0 per million, respectively, whereas quarterly baseline ASIRs ranged between 150.3 and 175.1 per million (incidence RR 0.93 [95% CI 0.78 to 1.12] to incidence RR 1.04 [95% CI 0.87 to 1.24]). We found no statistically significant level or slope changes between the projected and observed ASIRs for all new cancers (parameter estimate [β], level 4.98, 95% CI -15.1 to 25.04, p = 0.25), or when stratified by cancer type or by geographic area. Clinical trial enrolment rate was stable or increased during the pandemic compared with baseline (RR 1.22 [95% CI 0.70 to 2.13] to RR 1.71 [95% CI 1.01 to 2.89]). There was no difference in the proportion of patients with metastatic disease (RR 0.84 [95% CI 0.55 to 1.29] to RR 1.22 [0.84 to 1.79]), or who died within 30 days (RR 0.16 [95% CI 0.01 to 3.04] to RR 1.73 [95% CI 0.38 to 15.2]).

INTERPRETATION: We did not observe a statistically significant change in the incidence of childhood cancer, or in the proportion of children enrolling in a clinical trial, presenting with metastatic disease or who died early during the first 9 months of the COVID-19 pandemic, which suggests that access to health care in pediatric oncology was not reduced substantially in Canada.

PMID:34844937 | DOI:10.1503/cmaj.210659

BMJ Open Qual. 2021 Nov;10(4):e001603. doi: 10.1136/bmjoq-2021-001603.

ABSTRACT

BACKGROUND: Closing loops to complete diagnostic referrals remains a significant patient safety problem in most health systems, with 65%-73% failure rates and significant delays common despite years of improvement efforts, suggesting new approaches may be useful. Systems engineering (SE) methods increasingly are advocated in healthcare for their value in studying and redesigning complex processes.

OBJECTIVE: Conduct a formative SE analysis of process logic, variation, reliability and failures for completing diagnostic referrals originating in two primary care practices serving different demographics, using dermatology as an illustrating use case.

METHODS: An interdisciplinary team of clinicians, systems engineers, quality improvement specialists, and patient representatives collaborated to understand processes of initiating and completing diagnostic referrals. Cross-functional process maps were developed through iterative group interviews with an urban community-based health centre and a teaching practice within a large academic medical centre. Results were used to conduct an engineering process analysis, assess variation within and between practices, and identify common failure modes and potential solutions.

RESULTS: Processes to complete diagnostic referrals involve many sub-standard design constructs, with significant workflow variation between and within practices, statistical instability and special cause variation in completion rates and timeliness, and only 21% of all process activities estimated as value-add. Failure modes were similar between the two practices, with most process activities relying on low-reliability concepts (eg, reminders, workarounds, education and verification/inspection). Several opportunities were identified to incorporate higher reliability process constructs (eg, simplification, consolidation, standardisation, forcing functions, automation and opt-outs).

CONCLUSION: From a systems science perspective, diagnostic referral processes perform poorly in part because their fundamental designs are fraught with low-reliability characteristics and mental models, including formalised workaround and rework activities, suggesting a need for different approaches versus incremental improvement of existing processes. SE perspectives and methods offer new ways of thinking about patient safety problems, failures and potential solutions.

PMID:34844935 | DOI:10.1136/bmjoq-2021-001603

Eur Urol Focus. 2021 Nov 26:S2405-4569(21)00292-3. doi: 10.1016/j.euf.2021.11.001. Online ahead of print.

ABSTRACT

BACKGROUND: Unwarranted between-hospital variation is a persistent health care quality issue. It is unknown whether urology patients are prone to this variation.

OBJECTIVE: To examine between-hospital variation in mortality, readmission, and length of stay for all 22 urological All Patient Refined Diagnosis Related Groups (APR-DRGs).

DESIGN, SETTING, AND PARTICIPANTS: This study included administrative data from 320640 urological admissions in 99 (98%) Belgian acute-care hospitals between 2016 and 2018.

OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: We used hierarchical mixed-effect logistic regression models to estimate hospital-specific and APR-DRG-specific risk-standardised rates for in-hospital mortality, 30-d readmission, and length of stay above the APR-DRG-specific 90th percentile. Between-hospital variation was assessed based on the estimated variance components. Associations of outcomes with patient and hospital characteristics and time trends were examined.

RESULTS AND LIMITATIONS: Our analysis revealed important between-hospital variation in mortality, readmission, and length of stay for urological pathologies, particularly for medical diagnoses. Significant variation was shown in all three outcomes for kidney and urinary tract infections; other kidney and urinary tract diagnoses, signs, and symptoms; urinary stones and acquired upper urinary tract obstruction; and kidney and urinary tract procedures for nonmalignancy. Lowering of mortality rates in upper-quartile hospitals to the median could potentially save 41.5% of deaths in these hospitals, with the largest absolute gain for kidney and urinary tract infections and kidney and urinary tract malignancy. Limitations included a likely underestimation of readmission rates.

CONCLUSIONS: Urological patient outcomes are characterised by unwarranted between-hospital variation. We recommend improvement initiatives to prioritise kidney and urinary tract infections because of significant variation across the three outcomes and the largest potential gain in lives saved.

PATIENT SUMMARY: We found notable between-hospital variation in mortality, readmission, and length of stay for urological hospital admissions in Belgium. As much as 41.5% of deaths could potentially be avoided if underperforming hospitals improved. Targeting kidney and urinary tract infections could help reduce variation.

PMID:34844906 | DOI:10.1016/j.euf.2021.11.001

J Optom. 2021 Nov 26:S1888-4296(21)00065-0. doi: 10.1016/j.optom.2021.10.001. Online ahead of print.

ABSTRACT

OBJECTIVE: The main objective of this study was to obtain percentile curves of stereoacuity in arc seconds for a Spanish population aged between three and twelve years of age.

MATERIALS AND METHODS: A descriptive, observational and transversal study was conducted, which included children aged between three and twelve years of age who did not present with any known ocular and/or systemic diseases. The convenience sampling method was used to select the sample from three schools and one hospital in the Community of Madrid. The Bueno-Matilla Vision Unit’s random dot test was used to measure stereoacuity. A descriptive statistic was performed with the stereoacuity values that were obtained for the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles.

RESULTS: The stereoacuity values of 1300 children were analysed. In the 50th percentile curve, it was determined that stereoacuity values close to 40 sec/arc were present from four years of age, and at four years and nine months, stereoacuity values close to 28 sec/arc were already being observed within said percentile, with values that were similar to those expected in the adult population. A progressive increase was observed, reaching 19 sec/arc before six years of age, with this stereoacuity value becoming more established in children from seven years of age.

CONCLUSION: Although given the specific type of sampling that was performed it was not possible to generalise the results to the entire population, these percentile curves may aid paediatric professionals in their assessment of the development of this visual ability, which is indicative of the degree of development of binocular vision.

PMID:34844895 | DOI:10.1016/j.optom.2021.10.001

Clin Lymphoma Myeloma Leuk. 2021 Oct 31:S2152-2650(21)02388-0. doi: 10.1016/j.clml.2021.10.007. Online ahead of print.

ABSTRACT

POEMS syndrome, a rare plasma cell disorder, is challenging both in the diagnostic and therapeutic management. We present real word retrospective analysis of 108 cases analyzing clinical features and therapeutic modes. We compare our results with the available literature. This is the first description with such wide use of proteasome inhibitors in first line treatment. POEMS (Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare and challenging plasma cell disorder, both in the diagnostic and therapeutic management of the disease. Currently, the literature on POEMS is sparse with most evidence being case reports and small case studies. We present a retrospective real world experience of 108 patients with POEMS. We analyzed the clinical features and therapeutic interventions. Regarding clinical features, our findings demonstrated that skin lesions, thrombocythemia and polycythemia were present less frequently than reported previously. Regarding clinical interventions, this is one of the largest analyses of front line treatment in POEMS and the first one to include frequent utilization of proteasome inhibitors (37%). Bortezomib monotherapy was the most effective therapy achieving complete remission/very good partial remissions (CR/VGPR) in 69% of patients. Thirty percent of patients proceeded to planned autologous stem cell transplant (ASCT) as part of the front-line treatment resulting in statistically superior progression-free (PFS) and overall survival (OS) compared to non-ASCT treated patients (P= .003). In multivariate analysis, anemia, thrombocytopenia, and as age over 60 were associated with a negative impact on patient outcomes.

PMID:34844892 | DOI:10.1016/j.clml.2021.10.007

Surgeon. 2021 Nov 26:S1479-666X(21)00163-3. doi: 10.1016/j.surge.2021.09.006. Online ahead of print.

ABSTRACT

This retrospective study was performed to analyse if laterality of the retrieved living donor kidney had any effect on donor and recipient outcomes after hand assisted laparoscopic donor nephrectomy (HALDN). 739 donors who underwent HALDN between January 2006 and January 2018 at a large tertiary transplant centre in the United Kingdom were included. Donor outcomes in individuals undergoing right versus left HALDN were compared with respect to conversion rates, morbidity, warm and cold ischaemia times and recipient failure rates, vascular and ureteric complications. 604 (81.7%) underwent left HALDN and 135 (18.3%) underwent right HALDN, mean age was 47.1 years and 46.8 years respectively with comparable gender distribution. The operative time was shorter for the left side (p = 0.003) and improved during the study for the left but not the right side. In recipients who received left kidneys there were more early technical failures observed (8 versus 1) though not statistically significant. Most centres prefer performing a left nephrectomy and recipient surgeons prefer a left kidney for transplantation primarily because of having a longer vein. This large study provides reassurance that right HALDN nephrectomy is a safe procedure with similar outcomes to left HALDN.

PMID:34844890 | DOI:10.1016/j.surge.2021.09.006

Oral Surg Oral Med Oral Pathol Oral Radiol. 2021 Oct 23:S2212-4403(21)00690-8. doi: 10.1016/j.oooo.2021.10.011. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of the present study was to compare radiomorphometric measurements on panoramic images of patients with hyperthyroidism (HT) to those of a control population.

STUDY DESIGN: In this retrospective study, the mental index (MI), inferior panoramic mandibular index (PMI), antegonial index (AI), gonial index (GI), and mandibular cortical index (MCI) were evaluated on dental panoramic radiographs (DPRs) of 40 patients with HT and 40 healthy age- and sex-matched individuals and compared between the groups. Quantitative data (MI, PMI, AI, and GI) were analyzed with the Student t and Mann-Whitney U tests. Categorical data (MCI) were analyzed with the chi-square test.

RESULTS: Statistically significant differences between the patient and control groups were found for inferior PMI (P = .001) and AI (P = .017) values, with smaller mean values among the patients. However, the measurements of MI (P = .59) and GI (P = .164) and the MCI distribution (P = .13) were similar in both groups.

CONCLUSIONS: Evaluating the radiomorphometric indices of inferior PMI and AI on the DPRs of patients with HT who are at high risk of secondary osteoporosis could be helpful in the early diagnosis of osteoporotic changes and in formulating surgical treatment plans.

PMID:34844888 | DOI:10.1016/j.oooo.2021.10.011