Extra-articular Manifestations and Comorbidity in Rheumatoid Arthritis: Potential Impact of Pre–Rheumatoid Arthritis Prevention

Rheumatoid arthritis (RA) is associated with a wide variety of extra-articular manifestations and comorbidities, several of which can be organ- or even life-threatening. These extra-articular manifestations and comorbidities can also contribute to the physical disability and psychological morbidity of RA that lead to reduced quality of life, higher direct and indirect costs, and societal burden of the disease. Although the expansion of RA treatment options and adoption of treat-to-target approaches has reduced the incidence and severity of several nonarticular manifestations of RA, such as rheumatoid vasculitis and cardiovascular disease events, this does not seem to be shared by all RA comorbidities. Moreover, a number of highly prevalent and impactful RA-driven comorbidities, such as accelerated atherosclerosis, interstitial lung disease, and sarcopenia, can present clinically in the years before the manifestation of joint pain or observable synovitis. A larger proportion of patients with RA have atherosclerosis, myocardial dysfunction, interstitial lung disease, and sarcopenia that is subclinical in the preclinical and earliest clinical phases of RA, emphasizing the importance of targeting the pre-RA phase for the prevention of comorbidities that are often poorly responsive to treatment once they develop. Herein, we review the potential impact of pre-RA prevention on the incidence and burden of extra-articular manifestations and nonarticular comorbidities.     

Utilization and Adherence Patterns of Subcutaneously Administered Anti–Tumor Necrosis Factor Treatment Among Rheumatoid Arthritis Patients

Background

Adherence to therapy is a key requirement underlying achievement of clinical outcomes in randomized controlled drug registration trials. In postmarketing studies, comparison of adherence among therapies can become more complicated when drug dosing and administration schedules differ or when methods used to measure adherence are not consistently applied.

Objective

The objective of this exploratory study was to investigate a broad range of utilization and adherence outcomes associated with subcutaneous biologic treatments for rheumatoid arthritis (RA).

Methods

Adult patients (aged ≥18 years) exhibiting ≥2 claims with an RA diagnosis (code 714.x), at least 24 months of continuous medical and pharmacy eligibility, and 30-day supplies of adalimumab, etanercept, or golimumab were selected from the Optum Insight Clinformatics database. Adherence and utilization measures were calculated and compared across treatment groups.

Results

A total of 1532 adalimumab, 2099 etanercept, and 261 golimumab patients met inclusion criteria. Compared with both adalimumab and etanercept patients, golimumab patients were significantly more likely to have a medication possession ratio of ≥0.80 (82% vs 71% vs 62%; P < 0.001) and significantly less likely to have ≥4 late medication refills (6.9% vs 17.7% vs 26.1%; P < 0.001 for all). Etanercept patients had significantly greater refill intervals (37.7 vs 34.9 and 35.1 days) and had the lowest proportion of adherent fills (70% vs 77% and 75%) compared with both golimumab and adalimumab patients (P < 0.001 for all). Bivariate effects were reproduced in multivariate models that controlled for treatment duration.

Conclusions

A number of statistically significant medication adherence differences were observed among golimumab, adalimumab, and etanercept patients in treatment for RA. Overall, golimumab patients appeared to be the most adherent group. Findings may be partially attributable to golimumab patients’ likely increased disease severity, their prior experience with biologic medication, or golimumab’s once-monthly dosing schedule, which requires fewer administrations than both adalimumab and etanercept.     

THA—A Review of the Literature and Its Use in Treatment of Five Overdose Patients

Abstract

Background: This in vitro investigation was performed to study the adsorption characteristics of fluoxetine to activated charcoal and its commercial formulation Carbomix® powder in simulated gastric (pH=1.2) and intestinal (pH=7.2) fluid environments. Methods: Solutions containing fluoxetine and charcoal were incubated at 37°C for one hour. Reversed phase high performance liquid chromatography was used for the determination of free fluoxetine concentrations (range 0.2–8 ug/mL) in the diluted filtrate. Results: The maximum adsorption capacities at pH 1.2 for activated charcoal and Carbomix were 223 and 333?mg/g, respectively; at pH 7.2 they were 301 and 453?mg/g, respectively. The affinity constant values at pH 1.2 of activated charcoal and Carbomix were 441 and 122 L/g, respectively, while at pH 7.2 they were 482 and 589 L/g, respectively, indicating a strong binding of fluoxetine onto charcoals. Conclusions: Relative to the toxic and lethal doses in cases of fluoxetine intoxications, both types of charcoals tested were found effective for adsorption at gastric and intestinal pH. Adsorbed fluoxetine was significantly increased at intestinal pH, consistent with predominant adsorption of the undissociated form of the drug. We conclude that activated charcoal and Carbomix have adsorptive properties appropriate to medical treatment in cases of fluoxetine overdose     

E-Cigarette or Vaping Product Use–Associated Lung Injury: A Case Study and Review of the Literature

E-cigarette or vaping product use–associated lung injury (EVALI) has caused significant morbidity in the US population, including in many young patients. It is critical for all health-care providers to recognize symptoms and imaging findings associated with lung injury secondary to e-cigarette and vaping use. Nurses, both inpatient and outpatient, are in a unique position to be able to assess patients for vaping and e-cigarette use and educate patients on the dangers of continued use. Here, we describe the case of a 16-year-old male with a history of vaping presenting with clinical and radiographic features consistent with EVALI. We review the current literature on pathophysiology, diagnosis, management, and nursing implications of vaping-related lung disease.     

Safety and Effectiveness of Palliative Drug Treatment in the Last Days of Life—A Systematic Literature Review

Context

Dying patients commonly experience potentially distressing symptoms. Palliative care guidelines recommend opioids, anticholinergics, antipsychotics, and benzodiazepines for symptom relief.

Effects of Physical Exercise Interventions on Dual–Task Gait Speed Following Stroke: A Systematic Review and Meta–Analysis

Objectives

To estimate the treatment effects of exercise and/or gait training interventions on dual–task walking in people with stroke. The secondary objective was to conduct subgroup analyses to compare the treatment effects of interventions involving dual–task training to those without any dual–task training.

Effects of Combination of Proliferative Agents and Erythropoietin on Left Ventricular Remodeling Post–Myocardial Infarction

Erythropoietin (EPO) has the potential to improve ischemic tissue by mobilizing endothelial progenitor cells and enhancing neovascularization. We hypothesized that combining EPO with human chorionic gonadotrophin (hCG) would improve post–myocardial infarction (MI) effects synergistically. Methods: After MI, five to seven animals were randomly assigned to each of the following treatments: control; hCG; EPO; hCG + EPO, and prolactin (PRL) + EPO. Follow‐up echocardiograms were performed to assess cardiac structure and function. Apoptosis was determined by terminal deoxynucleotidyl transferase‐mediated dUTP nick end‐labeling (TUNEL) assay and western blot analysis for apoptosis‐related proteins, and cell proliferation by immunostaining for Ki67 and c‐kit cells. Results: The MI‐mediated increased chamber systolic dimension (p < 0.05 in controls) was attenuated by hCG, EPO, and hCG + EPO (p < 0.05 vs. control) but not PRL + EPO. Similarly all treatment groups, except PRL + EPO, reduced MI‐induced increases (p < 0.05 vs. control) in ejection fraction (EF). The functional improvement in the EPO‐treated groups was accompanied by increased capillary density. Apoptosis was markedly reduced in all treated groups. Significantly more cardiac c‐kit⁺ cells were found in the hCG + EPO group. Conclusion: Our findings revealed that EPO, hCG, or their combination ameliorate cardiac remodeling post‐MI. Whereas EPO stimulates neovascularization only and hCG + EPO stimulates c‐kit+ cell proliferation. These data suggest that combining mobilizing and proliferative agents adds to the durability and sustainability of cytokine‐based therapies for remodeling post‐MI. Clin Trans Sci 2011; Volume 4: 168–174     

Two Sides of the Same Coin? A Dual Multiple Criteria Decision Analysis of Novel Treatments Against Rheumatoid Arthritis in Physicians and Patients

PurposeAvailable treatment options for rheumatoid arthritis (RA) differ in important aspects. In this sense, each RA treatment option is accompanied by a spectrum of characteristics that collectively constitute its comprehensive “value,” as viewed from the physician's or the patient's perspective. The objective of this study was to perform a multiple criteria decision analysis of different RA treatments from the perspective of physicians and patients and to outline the respective aspects of value for each treatmentMethodsA literature review was performed for constructing a set of criteria (N = 8) for the multiple criteria decision analysis. Workshops for the elicitation of preferences occurred separately for physicians and patients. A performance matrix was populated via 2 network meta-analyses plus converged clinical opinion. Criteria were hierarchically classified by application of pairwise comparisons, and criteria weights were attributed by point allocation through convergence of opinions. Performances in both panels were scored by using a 100-point scale. A linear additive value function was used for the calculation of total value estimates.FindingsBoth panels provided their consensus. The hierarchical classification of attributes from the physician perspective placed the highest values on the criteria of severe adverse events, clinical efficacy, route of administration, and cost per year for the third-party payer. From the patient perspective, the highest ranking criteria were clinical efficacy, severe adverse events, percentage of patients remaining with the same targeted immune modulator for 1 year (“drug survival”), and cost per year for the third-party payer.ImplicationsIn an era of multiple options and varying preferences, RA treatments must be evaluated by taking into consideration patients’ preferences as well, as to cover the full spectrum of value elements rather than simply clinical outcomes. The results of this analysis show that physicians and patients share similarities but also marked differences in terms of the aspects of treatment that they perceive as more valuable.     

Importance of Time Point–Specific Indirect Treatment Comparisons of Osteoporosis Treatments: A Systematic Literature Review and Network Meta-Analyses

PurposeThe efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point–specific NMAs of osteoporosis treatments on variability in treatments’ onset of action caused by their different mechanisms of actions and trial designs.MethodsA systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.FindingsFor vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.ImplicationsThe importance of indirectly comparing available osteoporosis treatments using time point–specific NMAs was confirmed because indirect comparison results differed substantially across time points.     

Current and Emerging Treatment Modalities for Leber’s Hereditary Optic Neuropathy: A Review of the Literature

Introduction

The purpose of this review is to present the current and emerging treatment alternatives for Leber’s hereditary optic neuropathy (LHON), emphasizing the most recent use of idebenone and stem cells or gene therapy.

Methods

A comprehensive literature review was performed at the PubMed database regarding the various treatment modalities for LHON.

Results

Treatment modalities for LHON include nutritional supplements, activators of mitochondrial biogenesis, brimonidine, and symptomatic and supportive treatment, but nowadays attention is being paid to idebenone and gene therapy or stem cells.

Conclusion

The treatment of LHON remains challenging, given the nature of the disease and its prognosis.

     

Low-Voltage Electricity–Associated Burn Damage of Lung Parenchyma: Case Report and Literature Review

BackgroundElectrical injuries are common in daily life. The severity of electrical injury depends on the electric current, and assessing electrical damage is difficult because there appears to be no correlation between skin burns and visceral injury. We report a case of bilateral lung injury with pulmonary hemorrhage after exposure to low-voltage electricity.Case ReportA 23-year-old man was shocked by a low-voltage (110 V) electric current while at work. He had temporary loss of consciousness and twitching in the extremities, but soon regained consciousness and spontaneously stopped twitching. Electrical burn wounds were discovered on his back and forehead. Dyspnea and hemoptysis were noted. A computed tomography scan of the chest revealed patchy infiltration and consolidation of both lungs. The patient received treatment of tranexamic acid and prophylactic antibiotics for electricity-induced lung injury and pulmonary hemorrhage. Resolution of chest radiograph abnormalities was recorded on day 7. The mild dyspnea ceased approximately 2 weeks later.Why Should an Emergency Physician Be Aware of This?Electricity-induced lung injury should be considered in patients with electrical injury through a suspicious electrical current transmission pathway, respiratory symptoms, and corresponding imaging findings. Pulmonary complications can be serious and require early intervention.     

Understanding Nurses’ Knowledge and Attitudes Toward Pain Assessment in Dementia: A Literature Review

BackgroundPain is underrecognized and undertreated in patients with dementia. It has been suggested that nurses’ attitudinal barriers may contribute to the challenges surrounding pain assessment and management in dementia.AimsThis integrative literature review aims to identify and explore nurses’ knowledge and attitudes towards pain assessment in older people with dementia and how it may affect pain management in this patient group.MethodElectronic searches were conducted in Web of Science, MEDLINE, Scopus, ProQuest, PubMed, and EBSCOhost from January 2008 to December 2018 for articles specifically focusing on nurses’ knowledge and attitudes towards pain assessment in older patients with dementia.ResultsTen studies were included in the review after meeting the inclusion criteria. Data extracted from each study included study design, aims and objectives, setting/sample, findings, and limitations. Patients with dementia are at greater risk of experiencing underassessment, undertreatment, and delayed treatment of pain due to nurses’ knowledge deficits and uncertainty in the decision-making process. Nurses see providing comfort and reducing pain as ethical obligation. However, they find pain assessment a challenge due to the complexity of recognizing painful behaviors, and difficulty differentiating between pain and behavioral disturbances in dementia. Poor multidisciplinary communication, time constraints, and workload pressure, as well as uncertainty about opioid use, are important barriers to effective pain assessment and management among patients with dementia.ConclusionIt is essential that nurses gain confidence in distinguishing signs and symptoms of pain from behavioral changes in dementia. It is important to improve interdisciplinary communication and to get physicians to listen and prioritize pain assessment and management.     

In Vitro and Clinical Pharmacokinetic Studies of the Effects of Iron-containing Agents on Vadadustat,an Oral Hypoxia-inducible Factor–Prolyl Hydroxylase Inhibitor

PurposeVadadustat is an oral hypoxia-inducible factor–prolyl hydroxylase inhibitor approved in Japan for the treatment of anemia in chronic kidney disease. This study investigated drug–drug interactions between vadadustat and oral iron supplements or iron-containing phosphate binders commonly used in Japanese clinical practice by conducting in vitro mechanistic and clinical pharmacokinetic studies.MethodsIn the in vitro assessment, chelate formation of vadadustat with iron-containing agents was investigated in water and in a fed-state simulated intestinal fluid. Chelate formation was assessed by observation of a chelate-specific color, and the concentration of vadadustat was determined. In the single-dose, open-label, randomized, crossover clinical study, healthy male participants received 150 mg of vadadustat with or without oral iron-containing agents. Pharmacokinetic data were collected for up to 24 hours after vadadustat administration. Participants were monitored for adverse events during the study.FindingsVadadustat formed a chelate precipitate with ferrous sulfate and ferric nitrate, as shown by development of a specific bright orange color in water. The proportions of vadadustat dissolved in the supernatant were 2% and 18%, respectively. Vadadustat did not form a chelate precipitate in a fed-state simulated intestinal fluid in the presence of sodium ferrous citrate, ferric citrate hydrate, or sucroferric oxyhydroxide; the proportion of vadadustat in supernatant ranged from 63% to 89%. In the clinical pharmacokinetic study, coadministration of vadadustat with sodium ferrous citrate, ferric citrate hydrate, sucroferric oxyhydroxide, or ferrous sulfate decreased the AUC_0–∞ by 54.0% to 89.7% and C_max by 42.1% to 91.9%. No serious adverse events were reported.ImplicationsChelate formation of vadadustat with iron-containing agents was confirmed by in vitro analysis and depended on the type of iron-containing agent. The AUC_0–∞ and C_max of vadadustat decreased when coadministered with oral iron-containing agents. Our data suggest that the decreases in AUC_0–∞ and C_max are a result of chelation in the gastrointestinal tract; therefore, coadministration of iron-containing agents with vadadustat should use a dosing interval. ClinicalTrials.gov Identifier: NCT03645863.