Tag: pubmed

Musculoskelet Surg. 2022 May 17. doi: 10.1007/s12306-022-00748-9. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the outcomes of patients affected by proximal and middle one-third humeral shaft fractures treated with humeral helical plates.

MATERIAL AND METHODS: From October 2016 to June 2020, twenty-four (twenty women, four men) underwent humeral reduction and fixation with humeral helical plates (A.L.P.S.® Proximal Humeral Plating System, Zimmer Biomet) that preserve deltoid muscle insertion and reduce the risk of iatrogenic radial nerve injury. At one and six months after surgery, standard antero-posterior and lateral radiographs were obtained, and at last follow-up (eighteen months on average), clinical evaluation was performed through range of motion assessment, Constant score and DASH score questionnaires. Only descriptive statistical analysis was conducted.

RESULTS: At six months, all fractures have healed. At last follow-up (average eighteen months, 13-28) mean Constant score was 71 (range 33-96), mean Dash score was 19.2 (range 1.7-63). The average range of motion was calculated as follows: flexion 137.8° (range 90-180); abduction 125.8° (range 85-180°); external rotation 55° (range 20-80°), internal rotation at L3 (range between scapulae-trochanter). Three patients experienced temporary radial nerve palsy from injury, while in one case, a temporary iatrogenic palsy occurred.

CONCLUSIONS: In our opinion, the helical plate may be an effective surgical tool for management of proximal and middle one-third diaphyseal humeral fractures. The humeral helical plate allows stable fixation avoiding the deltoid tuberosity proximally and radial nerve distally, thus increasing the possibility of rapid functional recovery after surgery.

PMID:35579822 | DOI:10.1007/s12306-022-00748-9

Drug Saf. 2022 May;45(5):477-491. doi: 10.1007/s40264-022-01176-1. Epub 2022 May 17.

ABSTRACT

INTRODUCTION: Artificial intelligence based on machine learning has made large advancements in many fields of science and medicine but its impact on pharmacovigilance is yet unclear.

OBJECTIVE: The present study conducted a scoping review of the use of artificial intelligence based on machine learning to understand how it is used for pharmacovigilance tasks, characterize differences with other fields, and identify opportunities to improve pharmacovigilance through the use of machine learning.

DESIGN: The PubMed, Embase, Web of Science, and IEEE Xplore databases were searched to identify articles pertaining to the use of machine learning in pharmacovigilance published from the year 2000 to September 2021. After manual screening of 7744 abstracts, a total of 393 papers met the inclusion criteria for further analysis. Extraction of key data on study design, data sources, sample size, and machine learning methodology was performed. Studies with the characteristics of good machine learning practice were defined and manual review focused on identifying studies that fulfilled these criteria and results that showed promise.

RESULTS: The majority of studies (53%) were focused on detecting safety signals using traditional statistical methods. Of the studies that used more recent machine learning methods, 61% used off-the-shelf techniques with minor modifications. Temporal analysis revealed that newer methods such as deep learning have shown increased use in recent years. We found only 42 studies (10%) that reflect current best practices and trends in machine learning. In the subset of 154 papers that focused on data intake and ingestion, 30 (19%) were found to incorporate the same best practices.

CONCLUSION: Advances from artificial intelligence have yet to fully penetrate pharmacovigilance, although recent studies show signs that this may be changing.

PMID:35579812 | DOI:10.1007/s40264-022-01176-1

Drug Saf. 2022 May;45(5):493-510. doi: 10.1007/s40264-022-01158-3. Epub 2022 May 17.

ABSTRACT

Increasing availability of electronic health databases capturing real-world experiences with medical products has garnered much interest in their use for pharmacoepidemiologic and pharmacovigilance studies. The traditional practice of having numerous groups use single databases to accomplish similar tasks and address common questions about medical products can be made more efficient through well-coordinated multi-database studies, greatly facilitated through distributed data network (DDN) architectures. Access to larger amounts of electronic health data within DDNs has created a growing interest in using data-adaptive machine learning (ML) techniques that can automatically model complex associations in high-dimensional data with minimal human guidance. However, the siloed storage and diverse nature of the databases in DDNs create unique challenges for using ML. In this paper, we discuss opportunities, challenges, and considerations for applying ML in DDNs for pharmacoepidemiologic and pharmacovigilance studies. We first discuss major types of activities performed by DDNs and how ML may be used. Next, we discuss practical data-related factors influencing how DDNs work in practice. We then combine these discussions and jointly consider how opportunities for ML are affected by practical data-related factors for DDNs, leading to several challenges. We present different approaches for addressing these challenges and highlight efforts that real-world DDNs have taken or are currently taking to help mitigate them. Despite these challenges, the time is ripe for the emerging interest to use ML in DDNs, and the utility of these data-adaptive modeling techniques in pharmacoepidemiologic and pharmacovigilance studies will likely continue to increase in the coming years.

PMID:35579813 | DOI:10.1007/s40264-022-01158-3

Matern Child Health J. 2022 May 17. doi: 10.1007/s10995-022-03445-y. Online ahead of print.

ABSTRACT

OBJECTIVES: Although a number of early childhood development (ECD) interventions in healthcare settings in low- and middle-income countries (LMICs) have been developed to improve parent-directed outcomes and support ECD, their impact have yet to be established. This review assesses the effectiveness of healthcare-based ECD interventions in LMICs on the following key evidence-informed parenting outcomes affecting ECD: (1) responsive caregiving (2) cognitive stimulation and (3) parental mental health. Impacts on parental knowledge regarding ECD and parenting stress were also assessed.

METHODS: PubMed, PsycINFO, Scopus, CINAHL and Embase were searched. We included randomized controlled trials reporting effects of healthcare-based ECD interventions in LMICs on parent-directed outcomes in the first five years of life. Data extraction included study characteristics, design, sample size, participant characteristics, settings, intervention descriptions, and outcomes. Meta-analyses were conducted using random effects models.

RESULTS: 8 articles were included. Summary standardized mean differences demonstrated significant benefits of healthcare-based interventions in LMICs for improving: (1) cognitive stimulation (n = 4; SMD = 0.32; 95% CI: 0.08 to 0.56) and (2) ECD knowledge (n = 4; SMD = 0.44; 95% CI: 0.27 to 0.60). No significant effects were seen on maternal depression and parenting stress; only one study assessed parent-child interactions in the context of responsiveness. Limitations included small number of studies for moderation analysis, high heterogeneity, variability in measures used for outcomes and timing of assessments.

CONCLUSIONS FOR PRACTICE: Our results demonstrate statistically significant effects of healthcare-based interventions in LMICs on improving key evidence-based parenting outcomes and offers one promising strategy to support children reach their full developmental potential.

PMID:35579803 | DOI:10.1007/s10995-022-03445-y

Sci China Life Sci. 2022 May 13. doi: 10.1007/s11427-022-2104-3. Online ahead of print.

ABSTRACT

Patients with hormone receptor (HR)-positive tumors breast cancer usually experience a relatively low pathological complete response (pCR) to neoadjuvant chemotherapy (NAC). Here, we derived a 10-microRNA risk score (10-miRNA RS)-based model with better performance in the prediction of pCR and validated its relation with the disease-free survival (DFS) in 755 HR-positive breast cancer patients (273, 265, and 217 in the training, internal, and external validation sets, respectively). This model, presented as a nomogram, included four parameters: the 10-miRNA RS found in our previous study, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status, and volume transfer constant (K^trans). Favorable calibration and discrimination of 10-miRNA RS-based model with areas under the curve (AUC) of 0.865, 0.811, and 0.804 were shown in the training, internal, and external validation sets, respectively. Patients who have higher nomogram score (>92.2) with NAC treatment would have longer DFS (hazard ratio=0.57; 95%CI: 0.39-0.83; P=0.004). In summary, our data showed the 10-miRNA RS-based model could precisely identify more patients who can attain pCR to NAC, which may help clinicians formulate the personalized initial treatment strategy and consequently achieves better clinical prognosis for patients with HR-positive breast cancer.

PMID:35579777 | DOI:10.1007/s11427-022-2104-3

Int Ophthalmol. 2022 May 17. doi: 10.1007/s10792-022-02360-z. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the relationship between structure and function in moderate and advanced primary open-angle glaucoma (POAG) and to determine the accuracy of structure and vasculature for discriminating moderate from advanced POAG.

METHODS: In this cross-sectional study, 25 eyes with moderate and 40 eyes with advanced POAG were enrolled. All eyes underwent measurement of the thickness of circumpapillary retinal nerve fiber layer (cpRNFL) and macular ganglion cell complex (GCC), and optical coherence tomography angiography (OCTA) of the optic nerve head (ONH) and macula. Visual field (VF) was evaluated by Swedish interactive threshold algorithm and 24-2 and 10-2 patterns. The correlation between structure and vasculature and the mean deviation (MD) of the VFs was evaluated by a partial correlation coefficient. The area under the receiver operating characteristic curve (AUC) was applied for assessing the power of variables for discrimination moderate from advanced POAG.

RESULTS: Including all eyes, whole image vessel density (wiVD) of the ONH area, and vessel density (VD) in the inferior quadrant of perifovea were the parameters with significant correlation with the mean deviation (MD) of the VF 24-2 in OCTA of the ONH and macula (r = .649 and .397; p < .05). The greatest AUCs for discriminating moderate and advanced POAG belonged to VD of the inferior hemifield of ONH area (.886; 95% CI (.805, .967)), and VD in the inferior quadrant of perifovea (.833; 95% CI (.736, .930)) without statistically significant difference (.886 Versus .833; p = .601).

CONCLUSION: Among vascular parameters of the ONH area, wiVD had the strongest correlation with the MD of the VF 24-2 while VD of the inferior hemifield of the ONH area had the greatest AUC for discriminating moderate and advanced POAG. Vessel density in the inferior quadrant of perifovea had a significant correlation with the MD of VF 24-2 and also the greatest AUC for discriminating moderate and advanced POAG.

PMID:35579770 | DOI:10.1007/s10792-022-02360-z

J Echocardiogr. 2022 May 17. doi: 10.1007/s12574-022-00577-6. Online ahead of print.

ABSTRACT

BACKGROUND: The management of patients with asymptomatic significant aortic regurgitation (sAR) is often challenging and appropriate timing of aortic valve surgery remains controversial. Prognostic value of diastolic parameters has been demonstrated in several cardiac diseases. The aim of this study was to analyze the prognostic significance of the diastolic function evaluated by echocardiography, in asymptomatic patients with sAR.

METHODS: A total of 126 patients with asymptomatic sAR evaluated in the Heart Valve Clinic were retrospective included. Conventional echocardiographic systolic and diastolic function parameters were assessed. Left atrial (LA) auto-strain analysis was performed in a sub-group of 57 patients. A combined end-point of hospital admission due to heart failure, cardiovascular mortality, or aortic valve surgery was defined.

RESULTS: During a median follow-up of 34.1 (interquartile range 16.5-48.1) months, 25 (19.8%) patients reached the combined end-point. Univariate analysis showed that LV volumes, LV ejection fraction (LVEF), LV-GLS, E wave, E/e’ ratio, LA volume and LA reservoir strain (LASr) were significant predictors of events. Multivariate analysis that tested all classical echocardiographic variables statistically significant in the univariate model showed that LVEDV (HR = 1.02; 95% CI 1.01-1.03; p < 0.001) and E/e’ ratio (HR = 1.12; 95% CI 1.03-123; p = 0.01) were significant predictors of events. Kaplan-Meier curve, stratified by median value of LASr, showed that lower LASr values (less than median of 34%) were associated with higher rates of events (p = 0.013).

CONCLUSION: In this population of asymptomatic patients with sAR and normal LV systolic function, baseline diastolic parameters were prognostic markers of cardiovascular events; among them, LASr played a significant predictor role.

PMID:35579751 | DOI:10.1007/s12574-022-00577-6

Mol Biol Rep. 2022 May 17. doi: 10.1007/s11033-022-07488-w. Online ahead of print.

ABSTRACT

BACKGROUND: Scab caused by Venturia inaequalis (Cke.) Wint. is the most important fungal disease of apple. Fungicide application is a widely practiced method of disease control. However, the use of chemicals is costintensive, tedious, and ecologically unsafe. The development of genetic resistance and the breeding of resistant cultivars is the most reliable and safest option. One such source of scab resistance happens to be the variety ‘Shireen’, released from SKUAST-Kashmir. However, to date, the nature of resistance and its genetic control have not been characterized. Objective This research aimed to elucidate the genetic basis of scab resistance in Shireen.

METHODS: Genetic mapping of quantitative trait loci (QTL) for resistance to apple scab disease was performed using an F1 cross developed between the susceptible cultivar ‘StarKrimson’ and the resistant cultivar ‘Shireen’. The population was evaluated for two consecutive years. Further, six candidate genes were analyzed via quantitative real-time PCR, to determine their expression level in response to the pathogen infestation.

RESULTS: Genotyping and disease phenotyping of populations led us to identify two quantitative trait loci (QTLs), namely qRVI.SS-LG2.2019 and qRVI.SS-LG8.2019 on chromosomes 2 and 8 with LOD-values of 7.67 and 4.99 respectively, and six potential CDGs for the polygenic resistance in ‘Shireen’. The genomic region corresponding to the mapped QTLs in LG 2 and LG 8 of ‘Shireen’ was examined for candidate genes possibly related to scab resistance using in silico analysis.

CONCLUSION: The QTLs mapped in the genetic background of Shireen are the novel QTLs and may be transferred to desirable genetic backgrounds and provide opportunities for isolation and cloning of genes apart from their utility to achieve durable resistance to scab.

PMID:35579736 | DOI:10.1007/s11033-022-07488-w

JAMA. 2022 May 17;327(19):1875-1887. doi: 10.1001/jama.2022.5776.

ABSTRACT

IMPORTANCE: Transcatheter aortic valve implantation (TAVI) is a less invasive alternative to surgical aortic valve replacement and is the treatment of choice for patients at high operative risk. The role of TAVI in patients at lower risk is unclear.

OBJECTIVE: To determine whether TAVI is noninferior to surgery in patients at moderately increased operative risk.

DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial conducted at 34 UK centers, 913 patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk due to age or comorbidity were enrolled between April 2014 and April 2018 and followed up through April 2019.

INTERVENTIONS: TAVI using any valve with a CE mark (indicating conformity of the valve with all legal and safety requirements for sale throughout the European Economic Area) and any access route (n = 458) or surgical aortic valve replacement (surgery; n = 455).

MAIN OUTCOMES AND MEASURES: The primary outcome was all-cause mortality at 1 year. The primary hypothesis was that TAVI was noninferior to surgery, with a noninferiority margin of 5% for the upper limit of the 1-sided 97.5% CI for the absolute between-group difference in mortality. There were 36 secondary outcomes (30 reported herein), including duration of hospital stay, major bleeding events, vascular complications, conduction disturbance requiring pacemaker implantation, and aortic regurgitation.

RESULTS: Among 913 patients randomized (median age, 81 years [IQR, 78 to 84 years]; 424 [46%] were female; median Society of Thoracic Surgeons mortality risk score, 2.6% [IQR, 2.0% to 3.4%]), 912 (99.9%) completed follow-up and were included in the noninferiority analysis. At 1 year, there were 21 deaths (4.6%) in the TAVI group and 30 deaths (6.6%) in the surgery group, with an adjusted absolute risk difference of -2.0% (1-sided 97.5% CI, -∞ to 1.2%; P < .001 for noninferiority). Of 30 prespecified secondary outcomes reported herein, 24 showed no significant difference at 1 year. TAVI was associated with significantly shorter postprocedural hospitalization (median of 3 days [IQR, 2 to 5 days] vs 8 days [IQR, 6 to 13 days] in the surgery group). At 1 year, there were significantly fewer major bleeding events after TAVI compared with surgery (7.2% vs 20.2%, respectively; adjusted hazard ratio [HR], 0.33 [95% CI, 0.24 to 0.45]) but significantly more vascular complications (10.3% vs 2.4%; adjusted HR, 4.42 [95% CI, 2.54 to 7.71]), conduction disturbances requiring pacemaker implantation (14.2% vs 7.3%; adjusted HR, 2.05 [95% CI, 1.43 to 2.94]), and mild (38.3% vs 11.7%) or moderate (2.3% vs 0.6%) aortic regurgitation (adjusted odds ratio for mild, moderate, or severe [no instance of severe reported] aortic regurgitation combined vs none, 4.89 [95% CI, 3.08 to 7.75]).

CONCLUSIONS AND RELEVANCE: Among patients aged 70 years or older with severe, symptomatic aortic stenosis and moderately increased operative risk, TAVI was noninferior to surgery with respect to all-cause mortality at 1 year.

TRIAL REGISTRATION: isrctn.com Identifier: ISRCTN57819173.

PMID:35579641 | DOI:10.1001/jama.2022.5776

Diabetologia. 2022 May 17. doi: 10.1007/s00125-022-05715-4. Online ahead of print.

ABSTRACT

AIMS/HYPOTHESIS: Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes.

METHODS: We searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA_1c from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA_1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome.

RESULTS: Seven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA_1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from -17.71 mmol/mol (-1.62%) to -22.35 mmol/mol (-2.06%) vs placebo, -3.22 mmol/mol (-0.29%) to -10.06 mmol/mol (-0.92%) vs GLP-1 RAs, and -7.66 mmol/mol (-0.70%) to -12.02 mmol/mol (-1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality.

CONCLUSIONS/INTERPRETATION: A dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA_1c and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449.

PMID:35579691 | DOI:10.1007/s00125-022-05715-4