Psoriatic arthritis quality of life instrument: an assessment of sensitivity and response to change

OBJECTIVE: To assess responsiveness of the Psoriatic Arthritis Quality of Life tool (PsAQoL) and add further data regarding the construct validity of PsAQoL. METHODS: Twenty-eight patients with PsA underwent clinical assessment over a period of 6 months after change of disease modifying therapy, usually to methotrexate. Measures of outcome included PsAQoL, Health Assessment Questionnaire (HAQ), and assessment of disease activity. RESULTS: PsAQoL revealed significant change at 3 and 6 months. Standardized response mean was large at 3 months and small at 6 months. There was strong correlation with other patient-derived measures such as the HAQ and Patient Global at all timepoints. Disease Activity Score-28 and Physician Global showed a relationship with PsAQoL at 3 and 6 months, while a tender joint count relationship was seen only at 6 months. CONCLUSION: The PsAQoL now has responsiveness data and a measure of construct validity to sit alongside previously demonstrated reliability data. Our study has compared the change characteristcs within a group of patients. The next step in the development will require a placebo controlled trial to test discrimination between patients undergoing active treatment or taking placebo.     

Low minute ventilation episodes during anesthesia recovery following intraperitoneal surgery as detected by a non-invasive respiratory volume monitor

An electrical impedance-based noninvasive respiratory volume monitor (RVM) accurately reports minute volume, tidal volume and respiratory rate. Here we used the RVM to quantify the occurrence of and evaluate the ability of clinical factors to predict respiratory depression in the post-anesthesia care unit (PACU). RVM generated respiratory data were collected from spontaneously breathing patients following intraperitoneal surgeries under general anesthesia admitted to the PACU. Respiratory depression was defined as low minute ventilation episode (LMVe, <?40% predicted minute ventilation for at least 2 min). We evaluated for associations between clinical variables including minute ventilation prior to opioid administration and LMVe following the first PACU administration of opioid. Also assessed was a low respiratory rate (<?8 breaths per minute) as a proxy for LMVe. Of 107 patients, 38 (36%) had LMVe. Affected patients had greater intraoperative opioid dose, P?=?0.05. PACU opioids were administered to 45 (42.1%) subjects, of which 27 (25.2%) had LMVe (P?=?0.42) within 30 min following opioid. Pre-opioid minute ventilation <?70% of predicted normal value was associated with LMVe, P?<?0.01, (sensitivity?=?100%, specificity?=?81%).Low respiratory rate was a poor predictor of LMVe (sensitivity?=?11.8%). Other clinical variables (e.g., obstructive sleep apnea) were not found to be predictors of LMVe. Using RVM we identified that mild, clinically nondetectable, respiratory depression prior to opioid administration in the PACU was associated with the development of substantial subsequent respiratory depression during the PACU stay.     

A Model of Shared Mycobacteriology Testing Services: Lessons Learned

Objective

The need for public health laboratories (PHLs) to prioritize resources has led to increased interest in sharing diagnostic services. To address this concept for tuberculosis (TB) testing, the New York State Department of Health Wadsworth Center and the Rhode Island State Health Laboratories assessed the feasibility of shared services for the detection and characterization of Mycobacterium tuberculosis complex (MTBC).

Methods

We assessed multiple aspects of shared services including shipping, testing, reporting, and cost. Rhode Island State Health Laboratories shipped MTBC-positive specimens and isolates to Wadsworth Center. Average turnaround times were calculated and cost analysis was performed.

Results

Testing turnaround times were similar at both PHLs; however, the availability of conventional drug susceptibility testing (DST) results for Rhode Island primary specimens and isolates were extended by approximately four days of shipping time. An extended molecular testing panel was performed on every specimen submitted from Rhode Island State Health Laboratories to Wadsworth Center, and the total cost per specimen at Wadsworth Center was $177.12 less than at Rhode Island State Health Laboratories, plus shipping. Following a mid-study review, Wadsworth Center provided testing turnaround times for detection (same day), species determination of MTBC (same day), and molecular DST (2.5 days).

Conclusion

The collaboration between Wadsworth Center and Rhode Island State Health Laboratories to assess shared services of TB testing highlighted a successful model that may serve as a guideline for other PHLs. The provision of additional rapid testing at a lower cost demonstrated in this study could potentially improve patient management and result in significant cost and resource savings if used in similar models across the country.Public health laboratories (PHLs) are essential for disease prevention and control. They serve as a first line of defense by rapidly recognizing and averting the spread of communicable diseases. In addition, they play a critical role in providing specialized tests for low-incidence, high-risk diseases, such as tuberculosis (TB), rabies, and botulism.¹ Due to recent economic constraints, many PHLs have suffered financial pressures, including budget and staffing cuts. In some cases, PHLs have reduced or eliminated certain tests, creating a potential risk to the public''s health. As an alternative to the discontinuation of services, one suggested approach was the investigation of shared services with other PHLs in different jurisdictions through testing directories and pilot projects with assistance and support from the Centers for Disease Control and Prevention (CDC) and the Association of Public Health Laboratories (APHL).^2,3TB, which is caused by the bacteria Mycobacterium tuberculosis, is a disease for which PHLs play an important role by providing diagnostics that contribute to prevention. Despite an overall decline in cases, TB continues to be a significant burden on social, public health, and economic systems in the United States.⁴ Maintaining a comprehensive and efficient laboratory system is critical to the continued decline of TB rates and overall prevention and control of TB in the United States. However, providing comprehensive TB testing services is becoming increasingly expensive per case identified. Additionally, retaining technical proficiency remains a challenge, especially as many experienced personnel are lost to retirement and are difficult to replace.⁵In 2013, a total of 9,582 new TB cases were reported in the United States, with an incidence rate of 3.0 cases per 100,000 population. Only four states reported more than 500 cases of TB: California, Texas, New York, and Florida, accounting for half of all TB cases in the United States. The TB incidence rate in New York State (NYS) is 4.4 per 100,000 population.⁴ The overall number of TB cases in NYS has decreased slightly over time, while the number of drug-resistant TB (DR TB) cases has remained steady during the past five years. Additionally, the percentage of multidrug-resistant TB (MDR TB) cases in NYS has increased from 1.3% to 3.6% during the past five years.⁶ In contrast, the TB incidence rate in Rhode Island is 2.6 per 100,000 population, and the overall number of TB cases has remained constant; DR TB and MDR TB cases in Rhode Island are rare.^4,7 Given the low number of TB-positive specimens received each year in Rhode Island State Health Laboratories, developing an extensive, increasingly molecular-based, testing program for TB may not be cost effective. In contrast, a high proportion of specimens received each year by the NYS Department of Health Wadsworth Center are Mycobacterium tuberculosis complex (MTBC) positive, including DR TB and MDR TB cases, and an extensive testing program has been implemented.We assessed the feasibility of shared services for the detection and characterization of MTBC between Wadsworth Center and Rhode Island State Health Laboratories during a 10-month time period. Multiple aspects critical to the implementation of shared services were examined, including shipping, testing, reporting, and cost. During this project, Wadsworth Center provided services to Rhode Island State Health Laboratories for rapid detection of MTBC, MTBC species identification, rapid detection of mutations associated with rifampin and isoniazid resistance, and conventional drug susceptibility testing (DST). Importantly, this partnership allowed Wadsworth Center to assess its ability to share its extended testing capabilities with another PHL, determine if the additional services provided were beneficial to patient treatment and outcomes, and identify any potential issues with this testing approach.     

Probability of an Obese Person Attaining Normal Body Weight: Cohort Study Using Electronic Health Records

Objectives. We examined the probability of an obese person attaining normal body weight.Methods. We drew a sample of individuals aged 20 years and older from the United Kingdom’s Clinical Practice Research Datalink from 2004 to 2014. We analyzed data for 76 704 obese men and 99 791 obese women. We excluded participants who received bariatric surgery. We estimated the probability of attaining normal weight or 5% reduction in body weight.Results. During a maximum of 9 years’ follow-up, 1283 men and 2245 women attained normal body weight. In simple obesity (body mass index = 30.0–34.9 kg/m²), the annual probability of attaining normal weight was 1 in 210 for men and 1 in 124 for women, increasing to 1 in 1290 for men and 1 in 677 for women with morbid obesity (body mass index = 40.0–44.9 kg/m²). The annual probability of achieving a 5% weight reduction was 1 in 8 for men and 1 in 7 for women with morbid obesity.Conclusions. The probability of attaining normal weight or maintaining weight loss is low. Obesity treatment frameworks grounded in community-based weight management programs may be ineffective.Overweight and obesity are growing global health concerns.1 Strategies to control obesity emphasize obesity management and weight reduction as well as obesity prevention. In the United Kingdom, a national strategy report recommends that the management of obesity be an integral part of clinical practice.2 This envisages that patients may transition from obesity to a more healthy body weight. A target of 5% body weight loss is often recommended for obese individuals who intend to lose weight.3 However, access to weight management interventions may be limited,4 and weight management interventions have only small and poorly maintained effects on body weight.5,6 To understand the frequency with which reductions in body mass index (BMI, defined as weight in kilograms divided by the square of height in meters) may occur in a large population, we estimated the probability of an obese individual attaining normal body weight or a reduction of 5% in body weight.     

Selected ginsenosides of the protopanaxdiol series are novel positive allosteric modulators of P2X7 receptors

Background and Purpose

The P2X7 receptor is an ATP-gated ion channel predominantly expressed in immune cells and plays a key role in inflammatory processes. Ginseng is a well-known Chinese herb with both pro- and anti-inflammatory properties and many of its actions have been ascribed to constituent ginsenosides. We screened a number of ginsenoside compounds for pharmacological activity at P2X7 receptors, that might contribute to the reported immunomodulatory actions of ginseng.

Experimental Approach

We used several assays to measure responses of P2X7 receptors, ATP-mediated dye uptake, intracellular calcium measurement and whole-cell patch-clamp recordings. HEK-293 cells stably expressing human P2X7 receptors were used in addition to mouse macrophages endogenously expressing P2X7 receptors.

Key Results

Four ginsenosides of the protopanaxdiol series, Rb1, Rh2, Rd and the metabolite compound K (CK) potentiated the dye uptake responses of P2X7 receptors, whereas other ginsenosides tested were ineffective (1–10 μM). The potentiation was rapid in onset, required a threshold concentration of ATP (<50 μM) and had an EC₅₀ of 1.08 μM. CK markedly enhanced ATP-activated P2X7 currents, probably via an extracellular site of action. One of the consequences of this potentiation effect is a sustained rise in intracellular Ca²⁺ that could account for the decrease in cell viability in mouse macrophages after a combination of 500 μM ATP and 10 μM CK that are non-toxic when applied alone.

Conclusions and Implications

This study identifies selected ginsenosides as novel potent allosteric modulators of P2X7 channels that may account for some of the reported immune modulatory actions of protopanaxdiol ginsenosides in vivo.     

Trace elements in pacific Dunlin (Calidris alpina pacifica): patterns of accumulation and concentrations in kidneys and feathers

Ecotoxicology - Trace element concentrations were measured in Pacific Dunlin (Calidris alpina pacifica) to identify factors that influence accumulation and to assess toxicity risks. We report...     

Evaluation of safety and efficacy outcomes of direct oral anticoagulants versus warfarin in normal and extreme body weights for the treatment of atrial fibrillation or venous thromboembolism

Journal of Thrombosis and Thrombolysis - Despite evolving evidence, the use of direct oral anticoagulants (DOACs) in patients with extremes of body weight remains controversial. This study aimed to...