Long-term outcomes following a single corticosteroid injection for trigger finger

BACKGROUND: The outcomes of corticosteroid injection for trigger finger are well documented only with short-term follow-up. The purpose of this investigation was to determine the long-term effectiveness of a single injection and to examine predictors of success up to ten years after injection. METHODS: This case series analyzed 366 first-time corticosteroid injections in flexor tendon sheaths from January 2000 to December 2007 with a minimum follow-up duration of five years. Two hundred and forty patients (66%) were female, 161 patients (44%) had multiple trigger fingers, and eighty-eight patients (24%) had diabetes at the time of injection. The primary outcome of treatment failure was defined as subsequent injection or surgical trigger finger release of the affected digit. Medical records were reviewed, and any patients without documented failure or a return office visit in 2012 to 2013 were contacted by telephone regarding symptom recurrence and the need for additional treatment. Kaplan-Meier analyses with log-rank test and Cox regression analysis assessed the effect of baseline patient and disease characteristics on injection success. RESULTS: Forty-five percent of patients demonstrated long-term treatment success after a single injection. In the final regression model, the interaction of sex and the number of trigger fingers was the single predictor of treatment success. Exploring this association revealed a ten-year success rate of 56% for female patients presenting for the first time with a trigger finger compared with 35% in male patients presenting for the first time with a trigger finger, 39% in female patients with multiple trigger fingers, and 37% in male patients with multiple trigger fingers. Eighty-four percent of treatment failures occurred within the first two years following injection. Patient age, symptom type, and undifferentiated diabetes status were not predictive of treatment success. CONCLUSIONS: Female patients presenting with their first trigger finger have the highest rate of long-term treatment success after a single corticosteroid injection. Patients who continue to experience symptom relief two years after injection are likely to maintain long-term success. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence

Which comorbid conditions should we be analyzing as risk factors for healthcare-associated infections?

OBJECTIVETo determine which comorbid conditions are considered causally related to central-line associated bloodstream infection (CLABSI) and surgical-site infection (SSI) based on expert consensus.DESIGNUsing the Delphi method, we administered an iterative, 2-round survey to 9 infectious disease and infection control experts from the United States.METHODSBased on our selection of components from the Charlson and Elixhauser comorbidity indices, 35 different comorbid conditions were rated from 1 (not at all related) to 5 (strongly related) by each expert separately for CLABSI and SSI, based on perceived relatedness to the outcome. To assign expert consensus on causal relatedness for each comorbid condition, all 3 of the following criteria had to be met at the end of the second round: (1) a majority (&gt;50%) of experts rating the condition at 3 (somewhat related) or higher, (2) interquartile range (IQR)≤1, and (3) standard deviation (SD)≤1.RESULTSFrom round 1 to round 2, the IQR and SD, respectively, decreased for ratings of 21 of 35 (60%) and 33 of 35 (94%) comorbid conditions for CLABSI, and for 17 of 35 (49%) and 32 of 35 (91%) comorbid conditions for SSI, suggesting improvement in consensus among this group of experts. At the end of round 2, 13 of 35 (37%) and 17 of 35 (49%) comorbid conditions were perceived as causally related to CLABSI and SSI, respectively.CONCLUSIONSOur results have produced a list of comorbid conditions that should be analyzed as risk factors for and further explored for risk adjustment of CLABSI and SSI.Infect Control Hosp Epidemiol 2017;38:449–454</jats:sec

The influence of insurance status on access to and utilization of a tertiary hand surgery referral center

BACKGROUND: The purpose of this study was to systematically examine the impact of insurance status on access to and utilization of elective specialty hand surgical care. We hypothesized that patients with Medicaid insurance or those without insurance would have greater difficulty accessing care both in obtaining local surgical care and in reaching a tertiary center for appointments. METHODS: This retrospective cohort study included all new patients with orthopaedic hand problems (n = 3988) at a tertiary center in a twelve-month period. Patient insurance status was categorized and clinical complexity was quantified on an ordinal scale. The relationships of insurance status, clinical complexity, and distance traveled to appointments were quantified by means of statistical analysis. An assessment of barriers to accessing care stratified with regard to insurance status was completed through a survey of primary care physicians and an analysis of both patient arrival rates and operative rates at our tertiary center. RESULTS: Increasing clinical complexity significantly correlated (p < 0.001) with increasing driving distance to the appointment. Patients with Medicaid insurance were significantly less likely (p < 0.001) to present with problems of simple clinical complexity than patients with Medicare and those with private insurance. Primary care physicians reported that 62% of local surgeons accepted patients with Medicaid insurance and 100% of local surgeons accepted patients with private insurance. Forty-four percent of these primary care physicians reported that, if patients who were underinsured (i.e., patients with Medicaid insurance or no insurance) had been refused by community surgeons, they were unable to drive to our tertiary center because of limited personal resources. Patients with Medicaid insurance (26%) were significantly more likely (p < 0.001) to fail to arrive for appointments than patients with private insurance (11%), with no-show rates increasing with the greater distance required to reach the tertiary center. CONCLUSIONS: Economically disadvantaged patients face barriers to accessing specialty surgical care. Among patients with Medicaid coverage or no insurance, local surgical care is less likely to be offered and yet personal resources may limit a patient’s ability to reach distant centers for non-emergency care. LEVEL OF EVIDENCE: Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence

Plasma sTNFR1 and IL8 for prognostic enrichment in sepsis trials: a prospective cohort study.

BackgroundEnrichment strategies improve therapeutic targeting and trial efficiency, but enrichment factors for sepsis trials are lacking. We determined whether concentrations of soluble tumor necrosis factor receptor-1 (sTNFR1), interleukin-8 (IL8), and angiopoietin-2 (Ang2) could identify sepsis patients at higher mortality risk and serve as prognostic enrichment factors.MethodsIn a multicenter prospective cohort study of 400 critically ill septic patients, we derived and validated thresholds for each marker and expressed prognostic enrichment using risk differences (RD) of 30-day mortality as predictive values. We then used decision curve analysis to simulate the prognostic enrichment of each marker and compare different prognostic enrichment strategies.Measurements and main resultsAn admission sTNFR1 concentration &gt; 8861 pg/ml identified patients with increased mortality in both the derivation (RD 21.6%) and validation (RD 17.8%) populations. Among immunocompetent patients, an IL8 concentration &gt; 94 pg/ml identified patients with increased mortality in both the derivation (RD 17.7%) and validation (RD 27.0%) populations. An Ang2 level &gt; 9761 pg/ml identified patients at 21.3% and 12.3% increased risk of mortality in the derivation and validation populations, respectively. Using sTNFR1 or IL8 to select high-risk patients improved clinical trial power and efficiency compared to selecting patients with septic shock. Ang2 did not outperform septic shock as an enrichment factor.ConclusionsThresholds for sTNFR1 and IL8 consistently identified sepsis patients with higher mortality risk and may have utility for prognostic enrichment in sepsis trials

Design and implementation of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of human mesenchymal stem/stromal cells for the treatment of moderate-severe acute respiratory distress syndrome

Background: Despite advances in supportive care, moderate-severe acute respiratory distress syndrome (ARDS) is associated with high mortality rates, and novel therapies to treat this condition are needed. Compelling pre-clinical data from mouse, rat, sheep and ex vivo perfused human lung models support the use of human mesenchymal stem (stromal) cells (MSCs) as a novel intravenous therapy for the early treatment of ARDS. Methods: This article describes the study design and challenges encountered during the implementation and phase 1 component of the START (STem cells for ARDS Treatment) trial, a phase 1/2 trial of bone marrow-derived human MSCs for moderate-severe ARDS. A trial enrolling 69 subjects is planned (9 subjects in phase 1, 60 subjects in phase 2 treated with MSCs or placebo in a 2:1 ratio). Results: This report describes study design features that are unique to a phase 1 trial in critically ill subjects and the specific challenges of implementation of a cell-based therapy trial in the ICU. Conclusions: Experience gained during the design and implementation of the START study will be useful to investigators planning future phase 1 clinical trials based in the ICU, as well as trials of cell-based therapy for other acute illnesses. Trial registration Clinical Trials Registration: NCT01775774 and NCT02097641

Vitamin D deficiency contributes directly to the acute respiratory distress syndrome (ARDS)

Rationale: Vitamin D deficiency has been implicated as a pathogenic factor in sepsis and intensive therapy unit mortality but has not been assessed as a risk factor for acute respiratory distress syndrome (ARDS). Causality of these associations has never been demonstrated. Objectives: To determine if ARDS is associated with vitamin D deficiency in a clinical setting and to determine if vitamin D deficiency in experimental models of ARDS influences its severity. Methods: Human, murine and in vitro primary alveolar epithelial cell work were included in this study. Findings: Vitamin D deficiency (plasma 25(OH)D levels 600 genes. In a clinical setting, pharmacological repletion of vitamin D prior to oesophagectomy reduced the observed changes of in vivo measurements of alveolar capillary damage seen in deficient patients. Conclusions: Vitamin D deficiency is common in people who develop ARDS. This deficiency of vitamin D appears to contribute to the development of the condition, and approaches to correct vitamin D deficiency in patients at risk of ARDS should be developed

Consumer Response to Drug Risk Information:The Role of Positive Affect

Risk disclosure is an essential element of the marketing of prescription drugs and other medical products. This study examines how consumers respond to verbal information about the frequency and severity of medical-product risks and how media-induced affect can moderate such responses. The study finds that consumers tend to overestimate the actual likelihood of adverse events described with words such as “common” or “rare” (compared with the probabilities such terms are typically intended to convey) and that consumers tend to give little weight to such probability language when forming product use intentions. However, consumers in positive media-induced moods seem to engage in more nuanced evaluation of product risk information, weighing both frequency and severity information and using such information to make inferences about other product attributes (e.g., product efficacy). These findings suggest that medical marketers and regulators need to devise more effective means of communicating risk probability to consumers and that positive mood induction (e.g., by placing advertisements in upbeat media environments) can enhance consumers' ability to process product risk information

Structural basis for native agonist and synthetic inhibitor recognition by the Pseudomonas aeruginosa quorum sensing regulator PqsR (MvfR)

Bacterial populations co-ordinate gene expression collectively through quorum sensing (QS), a cell-to-cell communication mechanism employing diffusible signal molecules. The LysR-type transcriptional regulator (LTTR) protein PqsR (MvfR) is a key component of alkyl-quinolone (AQ)-dependent QS in Pseudomonas aeruginosa. PqsR is activated by 2-alkyl-4-quinolones including the Pseudomonas quinolone signal (PQS; 2-heptyl-3-hydroxy-4(1H)-quinolone), its precursor 2-heptyl-4- hydroxyquinoline (HHQ) and their C9 congeners, 2-nonyl-3-hydroxy-4(1H)-quinolone (C9-PQS) and 2-nonyl-4-hydroxyquinoline (NHQ). These drive the autoinduction of AQ biosynthesis and the up-regulation of key virulence determinants as a function of bacterial population density. Consequently, PqsR constitutes a potential target for novel antibacterial agents which attenuate infection through the blockade of virulence. Here we present the crystal structures of the PqsR co-inducer binding domain (CBD) and a complex with the native agonist NHQ. We show that the structure of the PqsR CBD has an unusually large ligand-binding pocket in which a native AQ agonist is stabilized entirely by hydrophobic interactions. Through a ligand-based design strategy we synthesized and evaluated a series of 50 AQ and novel quinazolinone (QZN) analogues and measured the impact on AQ biosynthesis, virulence gene expression and biofilm development. The simple exchange of two isosteres (OH for NH2) switches a QZN agonist to an antagonist with a concomitant impact on the induction of bacterial virulence factor production. We also determined the complex crystal structure of a QZN antagonist bound to PqsR revealing a similar orientation in the ligand binding pocket to the native agonist NHQ. This structure represents the first description of an LTTR-antagonist complex. Overall these studies present novel insights into LTTR ligand binding and ligand-based drug design and provide a chemical scaffold for further anti-P. aeruginosa virulence drug development by targeting the AQ receptor PqsR