Clinical predictors of donor antibody titre and correlation with recipient antibody response in a COVID-19 convalescent plasma clinical trial.

BACKGROUND: Convalescent plasma therapy for COVID-19 relies on transfer of anti-viral antibody from donors to recipients via plasma transfusion. The relationship between clinical characteristics and antibody response to COVID-19 is not well defined. We investigated predictors of convalescent antibody production and quantified recipient antibody response in a convalescent plasma therapy clinical trial. METHODS: Multivariable analysis of clinical and serological parameters in 103 confirmed COVID-19 convalescent plasma donors 28 days or more following symptom resolution was performed. Mixed-effects regression models with piecewise linear trends were used to characterize serial antibody responses in 10 convalescent plasma recipients with severe COVID-19. RESULTS: Donor antibody titres ranged from 0 to 1 : 3892 (anti-receptor binding domain (RBD)) and 0 to 1 : 3289 (anti-spike). Higher anti-RBD and anti-spike titres were associated with increased age, hospitalization for COVID-19, fever and absence of myalgia (all P < 0.05). Fatigue was significantly associated with anti-RBD (P = 0.03). In pairwise comparison amongst ABO blood types, AB donors had higher anti-RBD and anti-spike than O donors (P < 0.05). No toxicity was associated with plasma transfusion. Non-ECMO recipient anti-RBD antibody titre increased on average 31% per day during the first three days post-transfusion (P = 0.01) and anti-spike antibody titre by 40.3% (P = 0.02). CONCLUSION: Advanced age, fever, absence of myalgia, fatigue, blood type and hospitalization were associated with higher convalescent antibody titre to COVID-19. Despite variability in donor titre, 80% of convalescent plasma recipients showed significant increase in antibody levels post-transfusion. A more complete understanding of the dose-response effect of plasma transfusion amongst COVID-19-infected patients is needed.

Pharmacogenomics-Based Point-of-Care Clinical Decision Support Significantly Alters Drug Prescribing.

Changes in behavior are necessary to apply genomic discoveries to practice. We prospectively studied medication changes made by providers representing eight different medicine specialty clinics whose patients had submitted to preemptive pharmacogenomic genotyping. An institutional clinical decision support (CDS) system provided pharmacogenomic results using traffic light alerts: green = genomically favorable, yellow = genomic caution, red = high risk. The influence of pharmacogenomic alerts on prescribing behaviors was the primary endpoint. In all, 2,279 outpatient encounters were analyzed. Independent of other potential prescribing mediators, medications with high pharmacogenomic risk were changed significantly more often than prescription drugs lacking pharmacogenomic information (odds ratio (OR) = 26.2 (9.0-75.3), P < 0.0001). Medications with cautionary pharmacogenomic information were also changed more frequently (OR = 2.4 (1.7-3.5), P < 0.0001). No pharmacogenomically high-risk medications were prescribed during the entire study when physicians consulted the CDS tool. Pharmacogenomic information improved prescribing in patterns aimed at reducing patient risk, demonstrating that enhanced prescription decision-making is achievable through clinical integration of genomic medicine.

Patient Perceptions of Care as Influenced by a Large Institutional Pharmacogenomic Implementation Program.

Despite growing clinical use of genomic information, patient perceptions of genomic-based care are poorly understood. We prospectively studied patient-physician pairs who participated in an institutional pharmacogenomic implementation program. Trust/privacy/empathy/medical decision-making (MDM)/personalized care dimensions were assessed through patient surveys after clinic visits at which physicians had access to preemptive pharmacogenomic results (Likert scale, 1 = minimum/5 = maximum; mean [SD]). From 2012-2015, 1,261 surveys were issued to 507 patients, with 792 (62.8%) returned. Privacy, empathy, MDM, and personalized care scores were significantly higher after visits when physicians considered pharmacogenomic results. Importantly, personalized care scores were significantly higher after physicians used pharmacogenomic information to guide medication changes (4.0 [1.4] vs. 3.0 [1.6]; P < 0.001) compared with prescribing visits without genomic guidance. Multivariable modeling controlling for clinical factors confirmed personalized care scores were more favorable after visits with genomic-influenced prescribing (odds ratio [OR] = 3.26; 95% confidence interval [CI] = (1.31-8.14); P < 0.05). Physicians seem to individualize care when utilizing pharmacogenomic results and this decision-making augmentation is perceived positively by patients.

Impact of patient decision aids on appropriate and timely access to hip or knee arthroplasty for osteoarthritis: a randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of patient decision aids (PtDA) compared to usual education on appropriate and timely access to total joint arthroplasty in patients with osteoarthritis. METHOD: A randomized controlled trial (RCT) with patients undergoing orthopedic screening. Control and intervention arms received usual education; intervention arm also received a PtDA and a surgeon preference report. Wait times (primary outcome) were described using stratified Kaplan-Meier survival curves with patients censored at the time of death or loss to follow-up, and multivariable Cox proportional hazards regression. Secondary outcomes were compared using stratified Cochran-Mantel-Haenszel chi-squared tests. RESULTS: 343 patients were randomized to intervention (n = 174) or control (n = 169). The typical patient was 66 years old, retired, living with someone, and 51% had high school education or less. The intervention was associated with a trend towards reduction in wait time (hazard ratio (HR) 1.25, 95% confidence interval (CI) 0.99-1.60, P = 0.0653). Median wait times were 3 weeks shorter in intervention than in control at the community site with no difference at the academic site. Good decision quality was reached by 56.1% intervention and 44.5% control (Relative risk (RR) 1.25; 95% CI 1.00-1.56, P = 0.050). Surgery rates were 73.2% intervention and 80.5% controls (RR 0.91: 95% CI 0.81-1.03) with 12 intervention (7.3%) and eight control participants (4.9%) returning to have surgery within 2 years (P = 0.791). CONCLUSION: Compared to controls, decision aid recipients had shorter wait times at one site, fewer surgeries, and were more likely to reach good decision quality, but overall effect was not statistically significant. TRIALS REGISTRATION: The full trial protocol is available at ClinicalTrials.Gov (NCT00911638).

Clinical impact of treatment timing for chronic hepatitis C infection: a decision model.

Recent advances in the treatment of hepatitis C virus (HCV) infection have led to the availability of both highly efficacious interferon-containing and interferon-sparing regimens. However, the use of such therapies faces restrictions due to high costs. For patients who are medically eligible to receive interferon, the choice between the two will likely be impacted by preferences surrounding interferon, severity of disease, coverage policies and out-of-pocket costs. We developed a decision model to quantify the trade-offs between immediate, interferon-containing therapy and delayed, interferon-free therapy for patients with chronic, genotype 1 HCV infection. We projected the quality-adjusted life expectancy stratified by the presence or absence of cirrhosis for four strategies: (i) no treatment; (ii) immediate, one-time treatment with an interferon-containing regimen; (iii) immediate treatment as above with the opportunity for retreatment in patients who fail to achieve sustained virologic response with interferon-free therapy in 1 year; and (iv) delayed therapy with interferon-free therapy in 1 year. When compared to one-time immediate treatment with the interferon-containing regimen, delayed treatment with the interferon-free regimen in 1 year resulted in longer life expectancy, with a 0.2 quality-adjusted life year (QALY) increase in noncirrhotic patients, and a 1.1 QALY increase in patients with cirrhosis. This superiority in health benefits was lost when wait time for interferon-free therapy was greater than 3-3.2 years. In this modelling analysis, interferon-free therapy resulted in superior health benefits compared to immediate therapy with interferon until wait time exceeded 3-3.2 years. Such data can inform decision-making regarding treatment initiation for HCV as healthcare financing evolves.

Enlargement of the Internal Auditory Canal and Associated Posterior Fossa Anomalies in PHACES Association.

We noted enlargement of the internal auditory canal in several of our patients with posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects, eye abnormalities, and sternal or supraumbilical defects (PHACES) association and hence evaluated children with PHACES for the presence of an enlarged internal auditory canal and potential associated findings, including infantile hemangioma within the internal auditory canal, to understand the genesis of this enlargement. We reviewed our records to identify children with PHACES association who had been evaluated with MR imaging at our institutions. Imaging was reviewed for abnormal enhancement in the internal auditory canal, internal auditory canal enlargement, cerebellar hypoplasia, prominence of the petrous ridge, and deformity of the calvarium. We raise the possibility of an association between enlargement of the internal auditory canal in PHACES and a generalized malformation of the posterior fossa with cerebellar and calvarial hypoplasia.

A trial of inpatient indication based prescribing during computerized order entry with medications commonly used off-label.

BACKGROUND: Requiring indications for inpatient medication orders may improve the quality of prescribing and allow for easier placement of diagnoses on the problem list. Indications for inpatient medication orders are also required by some regulators. OBJECTIVE: This study assessed a clinical decision support (CDS) system designed to obtain indications and document problems during inpatient computerized physician order entry (CPOE) of medications frequently used off-label. METHODS: A convenience sample of three medications frequently used off-label were selected: the PPI lansoprazole; intravenous immune globulin, and recombinant Factor VIIa. Alerts triggered when a medication was ordered without an FDA approved indication in the problem list. The alerts prompted clinicians to enter either a labeled or off-label indication for the order. Chart review was used as the gold standard to assess the accuracy of clinician entered information. RESULTS: The PPI intervention generated 873 alerts during 60 days of operation; IVIG 55 alerts during alerts during 93 days; Factor VIIa 25 alerts during 175 days. Agreement between indications entered and chart review was 63% for PPI, 49% for IVIG, and 29% for Factor VIIa. The alerts for PPI, IVIG and Factor VIIa alerts produced accurate diagnoses for the problem list 9%, 16% and 24% respectively. Rates of off-label use measured by chart review were 87% for PPI, and 100% for IVIG and factor VIIa, which were higher than if measured using the ordering clinicians' indications. CONCLUSION: This trial of indication-based prescribing using CDS and CPOE produced less than optimal accuracy of the indication data as well as a low yield of accurate problems placed on the problem list. These results demonstrate the challenge inherent in obtaining accurate indication information during prescribing and should raise concerns over potential mandates for indication based prescribing and motivate further study of appropriate mechanisms to obtain indications during CPOE.

Nonprofit biomedical companies.

Nonprofit biomedical firms are an integrated market-based solution to improve incentives for investment in promising scientific areas that have high social value but minimal potential for profit. We briefly review the current market with an emphasis on the financing of innovative product development and propose ideas for new nonprofit companies centered on the health concerns of developed countries. We conclude with a suggestion that opportunities exist for nonprofit firms focused on cancer diagnostics, given the limitations of current financing incentives and ripe scientific opportunity.

Captive breeding of cheetahs in South Africa--30 years of data from the de Wildt Cheetah and Wildlife Centre.

The de Wildt Cheetah and Wildlife Centre was established in 1971 and the first cheetah cubs were born in 1975. During the period 1975-2005, 242 litters were born with a total of 785 cubs. Mean cub survival from 1 to 12 months and greater than 12 months of age was 71.3 and 66.2%, respectively. The majority of losses (84.9%) occurred during the first month postpartum whereas only 15.1% deaths took place between 1 and 12 months of age. Females were first bred at an age of approximately 3 years, reached maximum reproductive age at 6-8 years, where after fertility declined. Males reached peak reproduction at 6 and maintained this for up to 12 years of age. Male fertility was best correlated with sperm morphology. During recent years, for practical purposes, males were allocated to 'good' (>or=70% normal), 'fair' (40-70% normal) and 'poor' (<40% normal) categories according to sperm morphology count. The breeding males were selected from the good (preferably) and fair categories but poor category males were also used at times. Average litter sizes for 'good', 'fair' and 'poor' males were 3.44 (n = 21), 3.14 (n = 18) and 2.28 (n = 18), respectively. In females the heritability for litter size was high at 0.5848 (532 progeny, 1975-2007) and the maternal heritability for cub mortality was estimated to be 0.596. The data from the de Wildt Cheetah and Wildlife Centre and two other centres in the world (Kapama and Wassenaar) demonstrate that cheetah can be bred successfully in captivity.

Resident uncertainty in clinical decision making and impact on patient care: a qualitative study.

BACKGROUND: Little is known regarding how internal medicine residents manage uncertainty during decision making and subsequent effects on patient care. The aims of this study were to describe types of uncertainty faced by residents, strategies employed to manage uncertainty and effects on patient care. METHODS: Using critical incident technique, residents were asked to recall important clinical decisions during a recent call night, with probes to identify decisions made during uncertainty. They were also asked to report who they approached for advice. Three authors independently coded transcripts using the constant comparative method. RESULTS: The 42/50 (84%) interviewed residents reported 18 discrete critical incidents. Six categories emerged and mapped to the domains of the Beresford Model of Clinical Uncertainty: technical uncertainty (procedural skills, knowledge of indications); conceptual uncertainty (care transitions, diagnostic decision making and management conflict) and personal uncertainty (goals of care). In managing uncertainty, residents report a "hierarchy of assistance", using colleagues and literature for initial management, followed by senior residents, specialty fellows and, finally, the attending physician. Barriers to seeking the attending physician's input included the existence of a defined hierarchy for assistance and fears of losing autonomy, revealing knowledge gaps, and "being a bother". For 12 of the 18 cases reported, patient care was compromised: delay in procedure or escalation of care (n = 8); procedural complications (n = 2); and cardiac arrest (n = 2). CONCLUSION: Resident uncertainty results in delays of indicated care and, in some cases, patient harm. Despite the presence of a supervisory figure, residents adhere to a hierarchy when seeking advice in clinical matters.

A theoretical framework and competency-based approach to improving handoffs.

BACKGROUND: Once characterised by remarkable continuity of care by a familiar doctor, patient care today is delivered by multiple physicians with varying degrees of knowledge of the patient. Yet, few trainees learn the potential risks of these transitions and the strategies to improve patient care during handoffs. Little is known regarding the mechanisms by which handoffs affect patient care. RESULTS: Building on theoretical constructs from the social sciences and illustrated with a case study of the implementation of a night float service for the inpatient general medicine services at the University of Chicago, a conceptual framework is proposed to describe how handoffs affect both patients and physicians. CONCLUSION: Using this conceptual framework, recommendations are made for formal education based on the core competencies of communication and professionalism. Opportunities to educate trainees in acquiring these skills are described in the context of handoffs of patient care.

ACTH stimulation test in the captive cheetah (Acinonyx jubatus).

Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001). There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867). Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).

Complications of Body Piercing

"The trend of body piercing at sites other than the earlobe has grown in popularity in the past decade. The tongue; lips; nose; eyebrows; nipples; navel; and genitals may be pierced. Complications of body piercing include local and systemic infections; poor cosmesis; and foreign body rejection. Swelling and tooth fracture are common problems after tongue piercing. Minor infections; allergic contact dermatitis; keloid formation; and traumatic tearing may occur after piercing of the earlobe. ""High"" ear piercing through the ear cartilage is associated with more serious infections and disfigurement. Fluoroquinolone antibiotics are advised for treatment of auricular perichondritis because of their antipseudomonal activity. Many complications from piercing are body-site-specific or related to the piercing technique used. Navel; nipple; and genital piercings often have prolonged healing times. Family physicians should be prepared to address complications of body piercing and provide accurate information to patients."

Communication failures in patient sign-out and suggestions for improvement: a critical incident analysis.

BACKGROUND: The transfer of care for hospitalized patients between inpatient physicians is routinely mediated through written and verbal communication or "sign-out". This study aims to describe how communication failures during this process can lead to patient harm. METHODS: In interviews employing critical incident technique, first year resident physicians (interns) described (1) any adverse events or near misses due to suboptimal preceding patient sign-out; (2) the worst event due to suboptimal sign-out in which they were involved; and (3) suggestions to improve sign-out. All data were analyzed and categorized using the constant comparative method with independent review by three researchers. RESULTS: Twenty six interns caring for 82 patients were interviewed after receiving sign-out from another intern. Twenty five discrete incidents, all the result of communication failures during the preceding patient sign-out, and 21 worst events were described. Inter-rater agreement for categorization was high (kappa 0.78-1.00). Omitted content (such as medications, active problems, pending tests) or failure-prone communication processes (such as lack of face-to-face discussion) emerged as major categories of failed communication. In nearly all cases these failures led to uncertainty during decisions on patient care. Uncertainty may result in inefficient or suboptimal care such as repeat or unnecessary tests. Interns desired thorough but relevant face-to-face verbal sign-outs that reviewed anticipated issues. They preferred legible, accurate, updated, written sign-out sheets that included standard patient content such as code status or active and anticipated medical problems. CONCLUSION: Communication failures during sign-out often lead to uncertainty in decisions on patient care. These may result in inefficient or suboptimal care leading to patient harm.

Spectroscopic magnetic resonance imaging of a tumefactive demyelinating lesion.

Tumefactive demyelinating lesions can present with features similar, clinically and radiologically, to those of brain tumours. Proton MR spectroscopy has been increasingly used to characterize intracranial pathology. As the underlying pathophysiology of neoplasms is different from that of demyelinating disease, one may expect the metabolic composition of neoplasms to be significantly different from that of demyelinating lesions. We report a 49-year-old woman in whom the neurologic and radiologic findings were highly suggestive of a high-grade brain tumor, and the spectroscopic features were sufficiently similar to that of a tumor to convince the neurosurgeon to operate. This case emphasizes the need for caution when confronted with a patient who presents with a differential diagnosis of demyelinating lesion versus neoplasm.

The effect of storage conditions on samples for the evaluation of copper status in blesbok (Damaliscus pygargus phillipsi).

Investigaltions to determine the effect of sample storage on the concentration of copper in liver tissue and on the activity of erythrocyte superoxide dismutase were undertaken in preparation for a study of blesbok (Damaliscus pygargus phillipsi) that were suspected to be suffering from copper deficiency. Two liver samples were collected from each of 20 culled blesbok in a manner that simulated the collection of biopsies from the live animal. These samples were stored either in 10% formalin or frozen at -20 degrees C until analysed 4 1/2 months later. The effect of different methods of sample storage on superoxide dismutase activity was determined. Erythrocytes collected from 3 Jersey cows and 5 culled blesbok were washed and divided into 0.5 ml portions, stored at room temperature (approximately 20 degrees C), in a refrigerator (4 degrees C), frozen at -20 degrees C in a freezer, and in liquid nitrogen (-200 degrees C). An analysis of superoxide dismutase activity was undertaken using a commercial assay kit at intervals of 2-4 days until the levels of activity had fallen significantly. The copper concentration in formalin-preserved liver samples was significantly lower than that measured in frozen liver tissue apparently as a result of leaching. The activity of superoxide dismutase in cattle blood was unchanged for 4 days at room temperature but fell appreciably after 2 days at 4 degrees C and -20 degrees C. Enzyme activity remained unchanged for 200 days in erythrocytes stored in liquid nitrogen. Superoxide dismutase activity levels in healthy blesbok were considerably lower than those measured in Jersey cows and remained unaffected for up to 6 days in samples stored at 4 degrees C and 20 degrees C. The level of activity fell significantly thereafter. Samples stored in liquid nitrogen were unchanged after 40 days.

Impact of interpreter services on delivery of health care to limited-English-proficient patients.

OBJECTIVE: To determine whether professional interpreter services increase the delivery of health care to limited-English-proficient patients. DESIGN: Two-year retrospective cohort study during which professional interpreter services for Portuguese and Spanish-speaking patients were instituted between years one and two. Preventive and clinical service information was extracted from computerized medical records. SETTING: A large HMO in New England. PARTICIPANTS: A total of 4,380 adults continuously enrolled in a staff model health maintenance organization for the two years of the study, who either used the comprehensive interpreter services (interpreter service group [ISG]; N = 327) or were randomly selected into a 10% comparison group of all other eligible adults (comparison group [CG]; N = 4,053). MEASUREMENTS AND MAIN RESULTS: The measures were change in receipt of clinical services and preventive service use. Clinical service use and receipt of preventive services increased in both groups from year one to year two. Clinical service use increased significantly in the ISG compared to the CG for office visits (1.80 vs. 0.70; P <.01), prescriptions written (1.76 vs 0.53; P <.01), and prescriptions filled (2.33 vs. 0.86; P<.01). Rectal examinations increased significantly more in the ISG compared to the CG (0.26 vs. 0.02; P =.05) and disparities in rates of fecal occult blood testing, rectal exams, and flu immunization between Portuguese and Spanish-speaking patients and a comparison group were significantly reduced after the implementation of professional interpreter services. CONCLUSION: Professional interpreter services can increase delivery of health care to limited-English-speaking patients.