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Janus Kinase Inhibitors and Risk of Venous Thromboembolism: A Systematic Review and Meta-analysis

Mayo Clin Proc. 2021 Apr 8:S0025-6196(21)00054-9. doi: 10.1016/j.mayocp.2020.12.035. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess the risk of venous thromboembolism (VTE) in patients treated with Janus kinase (JAK) inhibitors in clinical trials.

PATIENTS AND METHODS: We performed a literature search of Ovid MEDLINE and ePub Ahead of Print, In-Process & Other Non-Indexed Citations, and Daily; Ovid EMBASE; Ovid Cochrane Central Register of Controlled Trials; Ovid Cochrane Database of Systematic Reviews; and Scopus, from inception to December 4, 2019, for randomized, placebo-controlled trials with JAK inhibitors as an intervention and reported adverse events. Odds ratio with 95% CI was calculated to estimate the VTE risk using a random effects model. Two independent reviewers screened and extracted data. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach was used to assess certainty in estimated VTE risk.

RESULTS: We included 29 trials (13,910 patients). No statistically significant association was found between use of JAK inhibitors and risk of VTE (odds ratio, 0.91; 95% CI, 0.57 to 1.47; P=.70; I2=0; low certainty because of serious imprecision). Results using Bayesian analysis were consistent with those of the primary analysis. Results of stratified and meta-regression analyses suggested no interaction by dose of drug, indication for treatment, or length of follow-up.

CONCLUSION: We found insufficient evidence to support an increased risk of JAK inhibitor-associated VTE based on currently available data.

PMID:33840525 | DOI:10.1016/j.mayocp.2020.12.035

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Patient-Reported Function and Quality of Life After Revision Total Knee Arthroplasty: An Analysis of 10,727 Patients from the NHS PROMs Program

J Arthroplasty. 2021 Mar 19:S0883-5403(21)00287-4. doi: 10.1016/j.arth.2021.03.037. Online ahead of print.

ABSTRACT

BACKGROUND: The aim of the study was to investigate changes in patient-reported outcome measures (PROMs) after revision total knee arthroplasty (rTKA).

METHODS: A total of 10,727 patients undergoing elective rTKA were recruited from the UK National Health Service PROMs data set from 2013 to 2019. PROMs were collected at baseline and six months to assess joint function (Oxford Knee Score, OKS) and quality of life (EQ-5D). Associations with a change in the OKS (COKS) were investigated through multiple linear regression.

RESULTS: The mean COKS was 12.4 (standard deviation 10.7) points. A total of 6776 of 10,329 (65.6%) patients demonstrated increase in the OKS above the minimal important change of 7.5 points. The median change in the EQ-5D utility was 0.227 (interquartile range 0.000 to 0.554). A total of 4917 of 9279 (53.0%) patients achieved a composite endpoint of improvement greater than the minimal important change for joint function and ‘better’ QoL as per the Paretian analysis. A total of 7477 of 10,727 (69.7%) patients reported satisfaction with rTKA. A total of 7947 of 10,727 (74.1%) patients felt surgery was a success. A total of 4888 of 10,632 (46.0%) patients reported one or more adverse events. A higher preoperative OKS was associated with a lower COKS (coefficient -0.63 [95% confidence interval -0.67 to -0.60]). Other factors associated with a lower COKS were postoperative complication(s), age under 60 years, longer duration of knee problems, patients who identified as disabled, problems in EQ-5D dimensions of anxiety/depression and self-care, comorbid conditions (circulatory problems, diabetes, and depression), and earlier year of procedure in the data set.

CONCLUSION: Two-thirds of patients experienced a meaningful improvement in joint function after rTKA. However, there was a high frequency of patient-reported complications. These findings may enable better informed discussion of the risks and benefits of discretionary rTKA.

PMID:33840536 | DOI:10.1016/j.arth.2021.03.037

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Heterotopic Ossification Negatively Influences Range of Motion After Revision Total Knee Arthroplasty

J Arthroplasty. 2021 Mar 11:S0883-5403(21)00263-1. doi: 10.1016/j.arth.2021.03.023. Online ahead of print.

ABSTRACT

BACKGROUND: The incidence of heterotopic ossification (HO) after total knee arthroplasty (TKA) varies and is of unclear clinical significance. This study aimed to identify the incidence of HO in patients undergoing revision TKA for either stiffness or aseptic loosening/instability and determine if the presence of HO is associated with inferior absolute range of motion (ROM) and ROM gains.

METHODS: Eighty-seven patients were prospectively enrolled and separated into 2 cohorts to evaluate ROM after revision TKA (2017-2019). Group 1 (N = 40) patients were revised for stiffness, while group 2 (N = 47) patients were revised for either aseptic loosening or instability. Goniometer-measured ROM values were obtained preoperatively and at 6 weeks, 6 months, and 1 year postoperatively. Statistical analysis included a Fisher’s exact test to assess for an association between preoperative HO and final ROM at 1 year after revision TKA.

RESULTS: HO was identified on preoperative radiographs in 17 patients (20%). There was a significantly higher rate of preoperative HO in patients revised for stiffness compared to patients revised for instability or loosening (30% vs 11%; P = .03). Five cases of HO qualitatively identified as most clinically severe were associated with lower ROM at each time point compared to the remainder of HO cases in this study cohort (P < .02).

CONCLUSION: The presence of HO is greater in patients undergoing revision TKA for stiffness. Additionally, HO severity appears to have a major effect on preoperative and postoperative ROM trajectory. This information should help guide patient expectations and highlight the need for a comprehensive, standardized classification system for HO.

PMID:33840538 | DOI:10.1016/j.arth.2021.03.023

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Radiographic evaluation of a bone substitute material in alveolar ridge preservation for maxillary removable immediate dentures: A randomized controlled trial

J Prosthet Dent. 2021 Apr 8:S0022-3913(21)00095-0. doi: 10.1016/j.prosdent.2021.02.013. Online ahead of print.

ABSTRACT

STATEMENT OF PROBLEM: Maxillary bone resorption after multiple extractions can jeopardize the success of an immediate denture, but whether bone volume preservation techniques are effective is unclear.

PURPOSE: The purpose of this randomized controlled trial was to evaluate the efficacy of socket grafting with a xenogenic bone substitute in participants receiving maxillary immediate removable complete dentures in terms of bone volume preservation (height and width of the bone ridge).

MATERIAL AND METHODS: The study was a single-blinded, randomized controlled clinical trial with 2 balanced parallel arms. Thirty-six participants who had Kennedy Class I edentulous posterior areas bilaterally for at least 3 months and required maxillary immediate removable complete dentures were enrolled. Duplicates of the removable complete denture were made and converted into radiographic and surgical guides. Participants allocated to the test group received deproteinized bovine bone mineral blended with 10% porcine collagen (DBBM-C) in the extraction sockets, and participants in the control group received no grafting material. With a radiographic guide in place, cone beam computed tomography scans were made 10 days after tooth extraction, when the immediate removable complete denture was delivered (D10, baseline), after 3 months (D90), and after 1 year (D365). The scans were superimposed, and measurements were made on the cross-sectional plane of each extraction site. The influence of various prognosis factors associated with bone volume preservation, including the location of tooth extraction, smoking habits, periodontal disease, and operator team, were analyzed.

RESULTS: Of 36 participants, 3 were lost to follow-up. The mean ±standard deviation loss of height of the buccal crest was 1.2 ±1.8 mm in the control group and 0.3 ±1.2 mm in the test group after 3 months of healing (P<.001) and 2.1 ±2.0 mm in the control group and 0.7 ±1.4 mm in the test group after 1 year of follow-up (P<.001). Mean ±standard deviation horizontal ridge width change was 1.3 ±1.4 mm in the control group and 0.5 ±0.8 mm in the test group after 3 months (P<.001) and 2.2 ±1.4 mm in the control group and 0.9 ±1.1 mm in the test group after 1 year of follow-up (P<.001). None of the other prognostic factors had a significant effect at either time period.

CONCLUSIONS: Grafting DBBM-C into the extraction socket after removing anterior teeth for immediate removable denture therapy resulted in significantly less vertical buccal crest and horizontal ridge resorption as compared with spontaneous socket healing after 1 year of follow-up. This procedure may be useful for preserving bone, especially when a fixed implant-supported prosthesis is planned.

PMID:33840514 | DOI:10.1016/j.prosdent.2021.02.013

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Association Between the CYP2C9 Genotype and Hypoglycemia Among Patients With Type 2 Diabetes Receiving Sulfonylurea Treatment: A Meta-analysis

Clin Ther. 2021 Apr 8:S0149-2918(21)00120-X. doi: 10.1016/j.clinthera.2021.03.008. Online ahead of print.

ABSTRACT

PURPOSE: Two common variants, CYP2C9*2 (Arg144Cys, rs1799853) and CYP2C9*3 (Ile359Leu, rs1057910), are known to reduce the catalytic function of the CYP2C9 enzyme. Because impaired catalytic function is likely to affect sulfonylurea metabolism, it is predictable that CYP2C9 loss-of-function alleles may increase the risk of sulfonylurea-induced hypoglycemia. This systematic review and meta-analysis aimed to assess the association between CYP2C9 genotype and hypoglycemia among patients with type 2 diabetes mellitus (T2DM) receiving sulfonylurea.

METHODS: We searched for studies on the association between CYP2C9 genotype and sulfonylurea-induced hypoglycemia among patients with T2DM, published through August 7, 2020, using PubMed, Web of Science, and EMBASE. Odds ratios (ORs) and 95% CIs were calculated.

FINDINGS: Five cohort studies and 2 case-control studies were included, and the total number of patients analyzed in this meta-analysis was 2769. The CYP2C9 variant alleles were associated with an increase in sulfonylurea-induced hypoglycemia compared with wild-type homozygote (OR = 1.24; 95% CI, 1.03-1.48). Compared with CYP2C9 wild-type homozygotes, CYP2C9*2 allele was associated with increased incidence of hypoglycemia (OR = 1.85; 95% CI, 1.18-2.89), whereas the CYP2C9*3 allele failed to show the statistical significance (OR = 1.67; 95% CI, 0.40-6.86; P = 0.48).

IMPLICATIONS: On the basis of these results, CYP2C9 genotyping may be useful for predicting the risk of hypoglycemia during sulfonylurea treatment for T2DM.

PMID:33840516 | DOI:10.1016/j.clinthera.2021.03.008

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Geographic Inequalities in Cardiovascular Mortality in the United States: 1999 to 2018

Mayo Clin Proc. 2021 Apr 8:S0025-6196(20)30987-3. doi: 10.1016/j.mayocp.2020.08.036. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the trends in cardiovascular, ischemic heart disease (IHD), stroke, and heart failure mortality in the stroke belt in comparison with the rest of the United States.

PATIENTS AND METHODS: We evaluated the nationwide mortality data of all Americans from the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research database from 1999 to 2018. Cause-specific deaths were identified in the stroke belt and nonstroke belt populations using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision codes. The relative percentage gap was estimated as the absolute difference computed relative to nonstroke belt mortality. Piecewise linear regression and age-period-cohort modeling were used to assess, respectively, the trends and to forecast mortality across the 2 regions.

RESULTS: The cardiovascular mortality rate (per 100,000 persons) was 288.3 (95% CI, 288.0 to 288.6; 3,684,273 deaths) in the stroke belt region and 251.2 (95% CI, 251.0 to 251.3; 13,296,164 deaths) in the nonstroke belt region. In the stroke belt region, age-adjusted mortality rates due to all cardiovascular causes (average annual percentage change [AAPC] in mortality rates, -2.4; 95% CI, -2.8 to -2.0), IHD (AAPC, -3.8; 95% CI, -4.2 to -3.5), and stroke (AAPC, -2.8; 95% CI, -3.4 to -2.1) declined from 1999 to 2018. A similar decline in cardiovascular (AAPC, -2.5; 95% CI, -3.0 to -2.0), IHD (AAPC, -4.0; 95% CI, -4.3 to -3.7), and stroke (AAPC, -2.9; 95% CI, -3.2 to -2.2) mortality was seen in the nonstroke belt region. There was no overall change in heart failure mortality in both regions (PAAPC>.05). The cardiovascular mortality gap was 11.8% in 1999 and 15.9% in 2018, with a modest reduction in absolute mortality rate difference (~7 deaths per 100,000 persons). These patterns were consistent across subgroups of age, sex, race, and urbanization status. An estimated 101,953 additional cardiovascular deaths need to be prevented from 2020 to 2025 in the stroke belt to ameliorate the gap between the 2 regions.

CONCLUSION: Despite the overall decline, substantial geographic disparities in cardiovascular mortality persist. Novel approaches are needed to attenuate the long-standing geographic inequalities in cardiovascular mortality in the United States, which are projected to increase.

PMID:33840523 | DOI:10.1016/j.mayocp.2020.08.036

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Evaluation of the retinal nerve fiber layer with optic coherence tomography in patients with alcohol use disorder

J Fr Ophtalmol. 2021 Apr 8:S0181-5512(21)00173-X. doi: 10.1016/j.jfo.2020.11.009. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aims to evaluate the retinal nerve fiber layer (RNFL) with optical coherence tomography (OCT) among patients with alcohol and tobacco use disorder.

METHODS: This study included 29 patients and 29 age and gender-matched healthy participants without alcohol dependency. The patients underwent full ophthalmologic examination including visual acuity, intraocular pressure, anterior segment and fundus examinations, and RNFL measurements taken with spectral-domain OCT. The RNFL values of the two groups were compared with each other.

RESULTS: In comparison to the control group, the RNFL was found to be thinner in all quadrants in the group with alcohol and tobacco dependency. The RNFL thinning in the superotemporal, temporal, and inferotemporal quadrants was found to be statistically significant (P-values 0.012, 0.040 and 0.005, respectively).

CONCLUSIONS: Chronic alcohol and tobacco use may cause RNFL thinning. Assessment of RNFL thinning by OCT among patients with alcohol and tobacco dependency might be used to identify visual morbidity.

PMID:33840492 | DOI:10.1016/j.jfo.2020.11.009

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Contribution of respiratory relaxation techniques during intravitreal injections: A pilot study

J Fr Ophtalmol. 2021 Apr 8:S0181-5512(21)00192-3. doi: 10.1016/j.jfo.2020.09.028. Online ahead of print.

ABSTRACT

PURPOSE: To study the effects of breathing techniques for anxiety, perceived pain, and patient satisfaction while receiving intravitreal injections.

METHOD: This prospective, randomized clinical study included patients admitted for intravitreal anti-VEGF injections. They were randomized into two groups: a relaxation group who listened to a prerecorded relaxation breathing session before and during the injection, and a control group who received the injection without a relaxation session. Statistical analysis was then performed to assess the factors influencing satisfaction, anxiety, and perceived pain.

RESULTS: We included one-hundred four patients in total: 52 in the relaxation group versus 52 in the control group. The relaxation group had a greater decrease in anxiety than the control group (P=0.03) but similar levels of pain (P=0.86). In total, 80.76% of patients in the relaxation group expressed the wish to have a relaxation session during their next injection. Multivariate analysis showed that the patient’s usual level of stress as well as the relaxation session affected the level of anxiety experienced before the injection.

CONCLUSION: Relaxation techniques before and during intravitreal injections decrease anxiety in patients without decreasing pain during IVT. Prerecorded relaxation breathing sessions are non-invasive, inexpensive, easy to set up, and reduce anxiety during intravitreal injections on an outpatient basis.

PMID:33840495 | DOI:10.1016/j.jfo.2020.09.028

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Antisocial Traits and Neuroticism as Predictors of Suicidal Behaviour in Borderline Personality Disorder: a Retrospective Study

Rev Colomb Psiquiatr. 2021 Apr 8:S0034-7450(21)00045-7. doi: 10.1016/j.rcp.2021.02.006. Online ahead of print.

ABSTRACT

INTRODUCTION: The spectrum of suicidal behaviour (SB) is nuclear in the clinic and management of borderline personality disorder (BPD). The pathological personality traits of BPD intervene as risk factors for SB in confluence with other clinical and sociodemographic variables associated with BPD. The objective of this work is to evaluate the specific personality traits of BPD that are related to SB.

METHODS: A cross-sectional, observational and retrospective study was carried out on a sample of 134 patients diagnosed with BPD according to DSM-5 criteria. The Millon-II, Zuckerman-Kuhlman and Barrat questionnaires were used to assess different personality parameters. Variable comparisons were made using the χ2 test and the Student’s t-test. The association between variables was analysed using multivariate logistic regression.

RESULTS: Statistically significant differences were observed between SB and related factors and the neuroticism-anxiety dimension in the Zuckerman-Kuhlman test. It is also significantly related to the phobic and antisocial subscale of the Millon-II. Impulsivity measured with the Zuckerman-Kuhlman and Barrat tests does not appear to be related to SB.

CONCLUSIONS: The results presented raise the role of phobic, antisocial and neuroticism traits as possible personality traits of BPD related to SB, suggesting an even greater importance within the relationship between BPD and SB than that of impulsivity. Looking to the future, longitudinal studies would increase the scientific evidence for the specified findings.

PMID:33840500 | DOI:10.1016/j.rcp.2021.02.006

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Deus ex machina? Demystifying rather than deifying machine learning

J Thorac Cardiovasc Surg. 2021 Mar 11:S0022-5223(21)00444-X. doi: 10.1016/j.jtcvs.2021.02.095. Online ahead of print.

NO ABSTRACT

PMID:33840471 | DOI:10.1016/j.jtcvs.2021.02.095