Nevin Manimala

J Neurol Neurosurg Psychiatry. 2021 Apr 13:jnnp-2020-325141. doi: 10.1136/jnnp-2020-325141. Online ahead of print.

ABSTRACT

OBJECTIVE: To describe decline in muscle strength and physical function in patients with sporadic inclusion body myositis (IBM).

METHODS: Manual muscle testing (MMT), quantitative muscle testing (QMT) and disability scoring using the IBM Functional Rating Scale (IBMFRS) were undertaken for 181 patients for up to 7.3 years. The relationship between MMT, QMT and IBMFRS composite scores and time from onset were examined using linear mixed effects models adjusted for gender and age of disease onset. Adaptive LASSO regression analysis was used to identify muscle groups that best predicted the time elapsed from onset. Cox proportional hazards regression was used to evaluate time to use of a mobility aid.

RESULTS: Multilevel modelling of change in percentage MMT, QMT and IBMFRS score over time yielded an average decline of 3.7% (95% CI 3.1% to 4.3%), 3.8% (95% CI 2.7% to 4.9%) and 6.3% (95% CI 5.5% to 7.2%) per year, respectively. The decline, however, was not linear, with steeper decline in the initial years. Older age of onset was associated with a more rapid IBMFRS decline (p=0.007), but did not influence the rate of MMT/QMT decline. Combination of selected muscle groups allowed for generation of single measures of patient progress (MMT and QMT factors). Median (IQR) time to using a mobility aid was 5.4 (3.6-9.2) years, significantly affected by greater age of onset (HR 1.06, 95% CI 1.04 to 1.09, p<0.001).

CONCLUSION: This prospective observational study represents the largest IBM cohort to date. Measures of patient progress evaluated in this study accurately predict disease progression in a reliable and useful way to be used in trial design.

PMID:33849999 | DOI:10.1136/jnnp-2020-325141

Hosp Pediatr. 2021 Apr 13:hpeds.2020-001636. doi: 10.1542/hpeds.2020-001636. Online ahead of print.

ABSTRACT

BACKGROUND: Penicillin allergy is reported in up to 10% of the general population; however, >90% of patients reporting an allergy are tolerant. Patients labeled as penicillin allergic have longer hospital stays, increased exposure to suboptimal antibiotics, and an increased risk of methicillin-resistant Staphylococcus aureus and Clostridioides difficile. The primary aim with our quality improvement initiative was to increase penicillin allergy delabeling to at least 10% among all hospitalized pediatric patients reporting a penicillin allergy with efforts directed toward patients determined to be low risk for true allergic reaction.

METHODS: Our quality improvement project included several interventions: the development of a multidisciplinary clinical care pathway to identify eligible patients, workflow optimization to support delabeling, an educational intervention, and participation in our institution’s quality improvement incentive program. Our interventions were targeted to facilitate appropriate delabeling by the primary hospital medicine team. Statistical process control charts were used to assess the impact of this intervention pre- and postpathway implementation.

RESULTS: After implementation of the clinical pathway, the percentage of patients admitted to hospital medicine delabeled of their penicillin allergy by discharge increased to 11.7%. More than one-half of those delabeled (51.2%) received a penicillin-based antimicrobial at time of discharge. There have been no adverse events or allergic reactions requiring emergency medication administration since pathway implementation.

CONCLUSIONS: Our quality improvement initiative successfully increased the rate of penicillin allergy delabeling among low-risk hospitalized pediatric patients, allowing for increased use of optimal antibiotics.

PMID:33849960 | DOI:10.1542/hpeds.2020-001636

J Immunother Cancer. 2021 Apr;9(4):e002501. doi: 10.1136/jitc-2021-002501.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) are the new standard of care in microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) metastatic colorectal cancer (mCRC). Since tumor response dynamic parameters already shown a strong association with survival outcomes in patients with mCRC treated with first-line therapy, we investigated the association of early tumor shrinkage (ETS) and depth of response (DoR) in patients with MSI-H/dMMR mCRC treated with ICIs.

METHODS: This is a retrospective, multicenter, cohort study in patients with dMMR and/or MSI-high mCRC treated with ICIs (anti-PD-1/PD-L1 with or without anti-CTLA-4 agents) with measurable disease and at least one post-baseline radiological disease reassessment. The Kaplan-Meier method and Cox proportional-hazards regression models were used for survival analyses. A maximally selected statistics method in a Cox regression model for progression-free survival (PFS) was used to determine the optimal cut-offs for ETS and DoR.

RESULTS: We included a total of 169 patients: 116 (68.6%) were treated with anti-PD-1 monotherapy, whereas 53 (31.4%) with anti-PD-1 plus anti-CTLA-4 agents. Patients with primary progressive disease (N=37, 21.9%), experienced an extremely poor overall survival (OS) and were evaluated separately. In patients with clinical benefit, we observed a significant association between ETS and DoR with both OS and PFS, and we identified a relative reduction of at least 1% as the optimal cut-off for ETS and a relative reduction of at least 50% as the optimal cut-off for DoR.

CONCLUSIONS: ETS and DoR are important prognostic factors in patients with MSI-high mCRC treated with ICIs that might be useful to design treatment intensification/deintensification strategies. A prospective validation of both is warranted.

PMID:33849927 | DOI:10.1136/jitc-2021-002501

Ann Rheum Dis. 2021 Apr 13:annrheumdis-2021-220142. doi: 10.1136/annrheumdis-2021-220142. Online ahead of print.

NO ABSTRACT

PMID:33849919 | DOI:10.1136/annrheumdis-2021-220142

Cancer Prev Res (Phila). 2021 Apr 13:canprevres.0581.2020. doi: 10.1158/1940-6207.CAPR-20-0581. Online ahead of print.

ABSTRACT

Current therapies for breast cancer prevention only prevent estrogen receptor positive (Er+) disease and toxicity limits use of these agents. Vitamin D is a potential prevention therapy for both Er+ and Er- disease and is safe with few side effects. This study evaluates the effect of one-year of vitamin D supplementation on mammographic density (MD), a biomarker of breast cancer risk in a multicenter randomized controlled trial. Premenopausal women with > 25% MD and no history of cancer, were randomly assigned to 2000IU of vitamin D or placebo orally daily for 1-year. Change in percent MD was evaluated using Cumulus software after all participants completed treatment. Three hundred women enrolled between 1/2011 and 12/2013 with a mean age of 43 and diverse ethnicity (14% Hispanic, 12% African American [AA]). Supplementation significantly increased vitamin D levels compared to placebo (14.5 ng/mL vs -1.6 ng/mL; p<0.0001) with all participants on the Vitamin D arm achieving vitamin D sufficiency at 12 months. Vitamin D was safe and well tolerated. After adjustment for baseline MD, the mean between-arm difference (vitamin D vs placebo) at 1 year was -0.75 [-.26, 1.76 p=0.56]. A greater effect was seen for women with >50% MD and AA women, although neither reached significance. This randomized controlled trial demonstrated significant improvement in vitamin D levels with 2000 IU for one year, with 100% of supplemented women achieving sufficiency. However, a null effect was seen regarding change in MD for premenopausal women (the primary outcome of the study).

PMID:33849913 | DOI:10.1158/1940-6207.CAPR-20-0581

BMJ Open. 2021 Apr 13;11(4):e047134. doi: 10.1136/bmjopen-2020-047134.

ABSTRACT

BACKGROUND: Cardiac rehabilitation (CR) decreases the morbidity and mortality risk among patients with cardiac diseases; however, the impact of CR on patients with diabetes remains underexplored. This is a protocol for a systematic review and meta-analysis methodology to explore if the effect of CR on mortality and morbidity is the same in patients with type 2 diabetes compared with patients without diabetes.

METHODS AND ANALYSIS: Interventional and non-interventional studies comparing the effect of CR, for at least 1 month, on all-cause mortality and cardiovascular outcomes including fatal and non-fatal myocardial infarction, revascularisation and rehospitalisation in adults with cardiac diseases will be deemed eligible for inclusion. Studies published between 1990 and 2020 will be searched in PubMed, Embase, Cochrane, CINAHL, Scopus and in registries for randomised controlled trials. Eligible studies will be selected using the Covidence software, and their salient details regarding the design, population, tested interventions and outcomes of interest will be gathered. The quality of studies to be deemed eligible and reviewed will be assessed using the Cochrane Collaboration and National Heart, Lung, and Blood Institute’s tools. The appraisal process will be based on the study design (interventional and non-interventional). In the meta-analysis step, the pooled effect of CR on the outcomes will be estimated. All meta-analyses will be done using the random-effects model approach (inverse-variance method). I ² and p value of χ² statistics will guide the heterogeneity assessment. Subgroup analyses will also be performed. The small study effect will be investigated by generating the funnel plots. The symmetry of the latter will be tested by performing Egger’s test.

ETHICS AND DISSEMINATION: The systematic review will use data from published literature; hence, no ethical approval will be required. Findings of the systematic review and meta-analysis will be published in peer-reviewed international journals and will be disseminated in local and international scientific meetings.

PROSPERO REGISTRATION NUMBER: CRD42020148832.

PMID:33849857 | DOI:10.1136/bmjopen-2020-047134

BMJ Open. 2021 Apr 13;11(4):e044949. doi: 10.1136/bmjopen-2020-044949.

ABSTRACT

INTRODUCTION: Surgical interventions can elicit neuroendocrine responses and sympathovagal imbalance, ultimately affecting cardiac autonomic function. Cardiac complications account for 30% of postoperative complications and are the leading cause of morbidity and mortality following non-cardiac surgery. One cardiovascular parameter, heart rate variability (HRV), has been found to be predictive of postoperative morbidity and mortality. HRV is defined as variation in time intervals between heartbeats and is affected by cardiac autonomic balance. Furthermore, altered HRV has been shown to predict cardiovascular events in non-surgical settings. In multiple studies, experimentally induced pain in healthy humans leads to reduced HRV suggesting a causal relationship. In a different studies, chronic pain has been associated with altered HRV, however, in the setting of clinical pain conditions, it remains unclear how much HRV impairment is due to pain itself versus autonomic changes related to analgesia. We aim to review the available evidence describing the association between postsurgical pain and HRV alterations in the early postoperative period.

METHODS AND ANALYSIS: We will conduct a scoping review of relevant studies using detailed searches of MEDLINE and EMBASE, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis. Included studies will involve participants undergoing non-cardiac surgery and investigate outcomes of (1) measures of pain intensity; (2) measures of HRV and (3) statistical assessment of association between #1 and #2. As secondary review outcomes included studies will also be examined for other cardiovascular events and for their attempts to control for analgesic treatment and presurgical HRV differences among treatment groups in the analysis. This work aims to synthesise available evidence to inform future research questions related to postsurgical pain and cardiac complications.

ETHICS AND DISSEMINATION: Ethics review and approval is not required for this review. The results will be submitted for publication in peer-reviewed journals.

PMID:33849852 | DOI:10.1136/bmjopen-2020-044949

BMJ Open. 2021 Apr 13;11(4):e040912. doi: 10.1136/bmjopen-2020-040912.

ABSTRACT

OBJECTIVE: To assess a possible interaction effect between physical activity and air pollution on first incidence of ischaemic heart disease (IHD).

DESIGN: Prospective cohort study.

SETTING: Umeå, Northern Sweden.

PARTICIPANTS: We studied 34 748 adult participants of Västerbotten Intervention Programme cohort from 1990 to January 2014. Annual particulate matter concentrations (PM_2.5 and PM₁₀) at the participants’ residential addresses were modelled and a questionnaire on frequency of exercise and active commuting was completed at baseline. Cox proportional hazards modelling was used to estimate (1) association with physical activity at different levels of air pollution and (2) the association with particulate matter at different levels of physical activity.

OUTCOME: First incidence of IHD.

RESULTS: Over a mean follow-up of 12.4 years, there were 1148 IHD cases. Overall, we observed an increased risk of IHD among individuals with higher concentrations of particles at their home address. Exercise at least twice a week was associated with a lower risk of IHD among participants with high residential PM_2.5 (hazard ratio (HR) 0.60; 95% CI: 0.44 to 0.82) and PM₁₀ (HR 0.55; 95% CI: 0.4 to 0.76). The same beneficial effect was not observed with low residential PM_2.5 (HR 0.94; 95% CI: 0.72 to 1.22) and PM₁₀ (HR 0.99; 95% CI: 0.76 to 1.29). An increased risk associated with higher long-term exposure to particles was only observed among participants that exercised in training clothes at most one a week and among those not performing any active commuting. However, only the interaction effect on HRs for exercise was statistically significant.

CONCLUSION: Exercise was associated with a lower risk of first incidence of IHD among individuals with higher residential particle concentrations. An air pollution-associated risk was only observed among those who exercised less. The findings support the promotion of physical activity and a mitigation of air pollution.

PMID:33849846 | DOI:10.1136/bmjopen-2020-040912

Nan Fang Yi Ke Da Xue Xue Bao. 2021 Mar 25;41(3):424-429. doi: 10.12122/j.issn.1673-4254.2021.03.16.

ABSTRACT

OBJECTIVE: To explore the changes of small-world network properties in patients with primary insomnia based on resting-state functional magnetic resonance imaging (rs-fMRI).

OBJECTIVE: The rs-MRI data and neurological scale data of 65 patients and 60 matched healthy controls were collected. The brain network was constructed using GRENTA software. SPSS software and network-based statistical analysis methods were used for statistical analysis.

OBJECTIVE: There was no significant difference between the two groups in terms of age, gender or education level (P > 0.05), but PSQI, HAMA and HAMD scale scores differed significantly between the two groups (P < 0.05). Both of the groups showed attributes of the small-world network. Compared with the control group, the patients with insomnia showed lower Cp, γ, Eloc, λ, connectivity, and σ of the small world network (P < 0.05).

OBJECTIVE: Patients with primary insomnia have lower global and local efficiencies than healthy individuals, and their ability to transmit information on the surface topology is impaired. Our data provide objective imaging evidences for the neuropathological mechanism of patients with primary insomnia.

PMID:33849835 | DOI:10.12122/j.issn.1673-4254.2021.03.16

Z Evid Fortbild Qual Gesundhwes. 2021 Apr 10:S1865-9217(21)00037-4. doi: 10.1016/j.zefq.2021.02.009. Online ahead of print.

ABSTRACT

INTRODUCTION: Examinations are a central element of the medical curriculum: they contribute significantly to the quality assurance of medical training and subsequent medical care. In order to meet the high expectations placed on examinations in terms of content, legal and organizational aspects, continuous quality assurance measures are necessary. The aim of this paper was to record and analyze the quality assurance measures implemented at the medical faculty of Heidelberg.

METHODS: We investigated quality indicators that are relevant to medical examinations -adequate choice of examination formats, blueprint/validity, reliability and distribution of grades, feedback to students, consequences of examinations – within the faculty examinations in the decentrally organized Heidelberg Curriculum Medicinale (HeiCuMed). In addition, the organizational structures in examination management were examined. For this purpose, interviews were conducted with teaching staff, students and the technical examination administration.

RESULTS: The surveys show that the quality indicators in HeiCuMed have already been met in many areas. Optimization work remains to be done concerning the criteria “adequate choice of examination formats”, “feedback to students” as well as the documentation of the examination process and the definition of substitution regulations.

DISCUSSION: Training courses, statistical analysis and accompanying research are essential for establishing additional innovative, practice-oriented examination formats. In order to improve feedback to students, formative assessments should be more intensively integrated into the curriculum. As a measure for structured quality-oriented examination management, it is also helpful to document the examination procedure and the staff assigned to it using templates.

CONCLUSION: Especially with decentralized examination management, the internal coordination of individual departments is of great importance in order to guarantee the quality of examinations. Regular surveys of the parties involved can be of support by collecting best-practice examples and deliver the respective information in handouts encouraging interdisciplinary exchange.

PMID:33849803 | DOI:10.1016/j.zefq.2021.02.009