Feasibility of Pharmacy-based Research Opportunity to Enhance Community Testing and Surveillance (PROTECTS).

BACKGROUND: Approximately 89% of the US population lives within five miles of a community pharmacy, which provides a network of geographically distributed recruitment nodes for testing and surveillance of infection and disease. OBJECTIVES: Establish feasibility of Pharmacy-based Research Opportunities To Enhance Community Testing and Surveillance (PROTECTS) in the context of SARS-CoV-2 infection in a community pharmacy setting with University of Kentucky serving as the coordinating center and research hub for sample analysis. METHODS: Two community pharmacies in Kentucky served as community-based recruitment sites to assess SARS-CoV-2 exposure through longitudinal (5 visits over 56 days) collection of nasal swabs and blood samples from subjects. RESULTS: Fifty subjects were recruited between May 2022 and December 2023 for longitudinal sample collection. Three phases of recruitment were investigated by first establishing standard operating procedures in an urban pharmacy, then expanding recruitment at a second pharmacy in a rural setting, and finally increasing recruitment at the urban pharmacy. During the first phase of recruitment, 12 participants were recruited. Of these participants, two never scheduled a visit after the initial screening. The median time for study completion from first to last visit within this phase was 59 days (IQR: 56-68 days). During the second phase of recruitment, eight of nine participants completed all five visits. The median time to complete all visits was 105 days (IQR: 98-112 days). During the ongoing third phase, 29 subjects were recruited, and 19 participants completed all required visits and the remainder continue to schedule follow-up appointments. CONCLUSION: Community pharmacies have a significant role in promoting public health. The geographic distribution of community pharmacies makes them appealing locations for recruitment of outpatient cohorts for local surveillance of infections and chronic inflammatory conditions with opportunities for broad implementation of this project for clinical trials in underserved communities.

Attributes of leadership skill development in high-performance pre-hospital medical teams: results of an international multi-service prospective study.

BACKGROUNDS: Team leadership skills of physicians working in high-performing medical teams are directly related to outcome. It is currently unclear how these skills can best be developed. Therefore, in this multi-national cross-sectional prospective study, we explored the development of these skills in relation to physician-, organization- and training characteristics of Helicopter Emergency Medicine Service (HEMS) physicians from services in Europe, the United States of America and Australia. METHODS: Physicians were asked to complete a survey regarding their HEMS service, training, and background as well as a full Leader Behavior Description Questionnaire (LBDQ). Primary outcomes were the 12 leadership subdomain scores as described in the LBDQ. Secondary outcome measures were the association of LBDQ subdomain scores with specific physician-, organization- or training characteristics and self-reported ways to improve leadership skills in HEMS physicians. RESULTS: In total, 120 HEMS physicians completed the questionnaire. Overall, leadership LBDQ subdomain scores were high (10 out of 12 subdomains exceeded 70% of the maximum score). Whereas physician characteristics such as experience or base-specialty were unrelated to leadership qualities, both organization- and training characteristics were important determinants of leadership skill development. Attention to leadership skills during service induction, ongoing leadership training, having standards in place to ensure (regular) scenario training and holding structured mission debriefs each correlated with multiple LBDQ subdomain scores. CONCLUSIONS: Ongoing training of leadership skills should be stimulated and facilitated by organizations as it contributes to higher levels of proficiency, which may translate into a positive effect on patient outcomes. TRIAL REGISTRATION: Not applicable.

Communicating our way to engaged volunteers: A mediated process model of volunteer communication, engagement, and commitment.

Retaining productive volunteers is an essential issue nonprofit organizations face, as volunteers help extend nonprofits' services to their target populations. The current study examined two facets of communication, perception of voice (i.e., upward communication) and satisfaction with communication (i.e., downward communication), as well as training, as important volunteer management practices with respect to facilitating volunteer engagement and commitment using both psychological contract and social exchange theories as the framework. One-hundred and seventy-one volunteers from two nonprofit organizations were surveyed to assess their satisfaction with the communication processes at their respective agencies, as well as their level of engagement, commitment, and perception of the training they received for their volunteer roles. Volunteer perceptions of both upward and downward communication were found to be indirectly related to organizational commitment through engagement. In addition, results indicated that volunteer training practices moderated the effects of upward and downward communication on engagement and commitment. Findings suggested that upward and downward communication are important predictors of volunteer engagement and commitment. Furthermore, providing training may help to strengthen these indirect effects.

Differentiation of distinct long-lived memory CD4 T cells in intestinal tissues after oral Listeria monocytogenes infection.

Mucosal antigen-specific CD4 T-cell responses to intestinal pathogens remain incompletely understood. Here we examined the CD4 T-cell response after oral infection with an internalin A 'murinized' Listeria monocytogenes (Lm). Oral Lm infection induced a robust endogenous listeriolysin O (LLO)-specific CD4 T-cell response with distinct phenotypic and functional characteristics in the intestine. Circulating LLO-specific CD4 T cells transiently expressed the 'gut-homing' integrin α4ß7 and accumulated in the intestinal lamina propria and epithelium where they were maintained independent of interleukin (IL)-15. The majority of intestinal LLO-specific CD4 T cells were CD27- Ly6C- and CD69+ CD103- while the lymphoid LLO-specific CD4 T cells were heterogeneous based on CD27 and Ly6C expression and predominately CD69-. LLO-specific effector CD4 T cells transitioned into a long-lived memory population that phenotypically resembled their parent effectors and displayed hallmarks of residency. In addition, intestinal effector and memory CD4 T cells showed a predominant polyfunctional Th1 profile producing IFNγ, TNFα, and IL-2 at high levels with minimal but detectable levels of IL-17A. Depletion of CD4 T cells in immunized mice led to elevated bacterial burden after challenge infection highlighting a critical role for memory CD4 T cells in controlling intestinal intracellular pathogens.

Effect of fat free mass on serum and plasma BDNF concentrations during exercise and recovery in healthy young men.

Exercise results in release of brain derived neurotrophic factor into the circulation; however, little is known about the changes in serum and plasma brain derived neurotrophic factor concentrations and factors influencing brain derived neurotrophic factor during exercise and recovery. Serum (n=23) and plasma (n=10) brain derived neurotrophic factor concentrations were measured in healthy young men at rest, during steady-rate and after exercise to determine the maximum aerobic power. A two-way analysis of variance was used to investigate brain derived neurotrophic factor levels in blood during exercise and recovery, with one between-subject factor (a median split on: age, height, body mass, fat free mass, body mass index and aerobic fitness), and one within-subject factor (time). Serum brain derived neurotrophic factor concentrations increased in response to exercise and declined rapidly in recovery. Plasma brain derived neurotrophic factor had a greater proportional increase relative to exhaustive exercise compared with serum brain derived neurotrophic factor and was slower to return to near baseline values. There was a significant group-by-time interaction indicating a greater release and faster recovery for serum brain derived neurotrophic factor in high- compared with low-fat free mass individuals.

Shoulder arthroplasty. Part 1: Prosthesis terminology and classification.

Shoulder arthroplasty is the third most common joint replacement procedure in the UK, and there are a number of different implant options available to surgeons to treat a variety of shoulder disorders. With an increasing burden placed on clinical follow-up, more patients are remaining under the care of their general practitioners and musculoskeletal triage assessment services and are not necessarily being seen by specialists. Referrals to orthopaedic specialists are therefore often prompted by radiological reports describing evidence of implant failure. This article is the first of two reviews on shoulder arthroplasty, concentrating on implant features and the indications for their use. The second article will address the modes of failure of shoulder arthroplasty and describe the relevant associated radiological features.

Shoulder arthroplasty. Part 2: normal and abnormal radiographic findings.

Frequently, the decision made by general practitioners or musculoskeletal triage assessment services to refer patients for specialist review is initiated by a radiological report. Following shoulder arthroplasty it is important to ensure that any patient with asymptomatic evidence of a failing prosthesis is referred for review so that revision surgery can be contemplated and planned before the situation becomes unsalvageable. The first paper in this series described the various types of shoulder arthroplasty and indications for each. This follow-up paper will concentrate on their modes of failure and the associated radiographic features, and is aimed at radiology trainees and non-musculoskeletal specialist radiologists.

Ten-year clinical follow-up of a cohort of 51 patients with macroprolactinemia establishes it as a benign variant.

CONTEXT: Macroprolactinemia is a common finding in patients with hyperprolactinemia. There are no published long-term follow-up studies. OBJECTIVE: The aim of this study was to describe findings after prolonged follow-up in a previously published cohort of patients with macroprolactinemia. STUDY POPULATION: We studied 51 patients identified as having macroprolactinemia after polyethylene glycol precipitation. DESIGN: Clinical assessment and serum prolactin assay were repeated in 51 patients with macroprolactinemia after a median follow-up of 9.9 yr (range, 9-11 yr). RESULTS: Median age at presentation was 41 yr (range, 18-55 yr). Mean serum prolactin concentration at presentation was 1885 mU/liter, and after follow-up 1370 mU/liter. At follow-up, headache had been experienced in 12 patients (24%) and oligomenorrhea in five (10%). Galactorrhea was present in only two patients (4%). No visual deterioration was noted in 50 patients. One had a transient bitemporal hemianopia. No patients developed an autoimmune condition. Microadenoma had been identified in four patients at presentation with no new pituitary imaging abnormalities identified at follow-up. CONCLUSIONS: During prolonged follow-up, no symptomatic progression was noted in any of our patients. This study suggests that patients with macroprolactinemia and normal concentrations of monomeric prolactin can be reassured, and extended endocrine review of such patients is not required.

Is there value in routine screening for Cushing's syndrome in patients with diabetes?

CONTEXT: Subclinical Cushing's syndrome has been described among diabetic populations in recent years, but no consensus has emerged about the value of screening. METHODS: We enrolled 201 consecutive patients attending our diabetes clinic and 79 controls. Patients with at least two of the following three criteria were offered screening using a 2300 h salivary cortisol test: glycosylated hemoglobin of at least 7%, body mass index of at least 25 kg/m(2), and a history of hypertension or blood pressure of at least 140/90 mm Hg. Results are expressed as mean +/- sem. RESULTS: Mean nighttime salivary cortisol levels were similar in the two groups (8.5 +/- 1.0 nmol/liter for diabetic patients vs. 5.8 +/- 1.0 nmol/liter for controls). Forty-seven patients (23%) had a value of at least 10 nmol/liter, which was set as a conservative threshold above which further investigation would be performed. Thirty-five (75%) agreed to further testing with a 1-mg overnight dexamethasone test. Of the remaining 12 patients, 10 were followed up clinically for at least 1 yr, and no evidence was found of the syndrome evolving. In 28 patients, serum cortisol suppressed to 60 nmol/liter or less. Of the seven patients who failed this test, four agreed to a 2 mg/d 48-h dexamethasone test, with serum cortisol suppressing to 60 nmol/liter or less in all four. Three declined this test but had normal 24-h urinary free cortisol levels. No patient had clinical features of hypercortisolism. CONCLUSIONS: The 1-3% detection rates of three recently published series have not been realized at our center where we studied a group using criteria making patients more likely to have hypercortisolism. Our results do not support the validity of screening patients without clinical features of Cushing's syndrome in the diabetes clinic.

Long term effect of external pituitary irradiation on IGF1 levels in patients with acromegaly free of adjunctive treatment.

OBJECTIVE: It is established that external pituitary irradiation (EPI) effectively reduces serum GH levels in acromegaly. However, its effect in normalising serum IGF1 has been disputed. We looked at the number of our patients who achieved persistently normal IGF1 levels whilst free of adjunctive treatment for at least 1 year after EPI. PATIENTS AND DESIGN: We identified 63 acromegalic patients between 1964 and 2004 who received EPI. Six were excluded: three had surgery after EPI, two had no medical records available, and one had a pituitary Yttrium implant. MEASUREMENTS: Patients received 4500-5000 cGy in fractionated doses. IGF1 levels were correlated with their respective age-related reference ranges. RESULTS: After EPI, the number of patients with normal IGF1 and free of adjunctive medical treatment for at least 1 year were four patients by 3 years, nine patients by 5 years and seventeen by 10 years, with the current number of 25/57 (44%). Concordance between IGF1 levels and random GH dropped from 90% at the time of EPI to 65% at 3 years, 66% at 5 years and 71% at 10 years. CONCLUSIONS: We have demonstrated that, with time, EPI achieves a normal IGF1 in significant numbers of patients with acromegaly, thus obviating the need for life-long expensive medical therapy. For each patient this benefit has to be weighed against the possibility of new hypopituitarism as a result of the treatment. Any decision to use EPI is easier in the context of pre-existent hypopituitarism.

The hip in osteochondrodysplasias: general rules for diagnosis and treatment.

The management of hip pathology in osteochondrodysplasia (skeletal dysplasia) is complex and a multidisciplinary approach is vital. Thorough clinical assessment and knowledge of the natural history of the different disorders provides the basis for this.

Pulsed infrared light therapy does not increase nitric oxide concentration in the blood of patients with type 1 and type 2 diabetes mellitus.

The purpose of this study was to determine if NO blood concentrations increased acutely following an 8-week course of pulsed infrared light therapy (PILT) which could be linked to an improvement in peripheral protective sensation (PPS) in patients who have profound chronic diabetic peripheral neuropathy. A total of 22 subjects with the diagnosis of type 1 (N = 2) or type 2 (N = 20) diabetes participated in the study. PILT was administered to one foot chosen at random with the other foot serving as a within-subject control (no treatment). Patients underwent 24 treatments (3 times/week, for 8 weeks) for 30 min per treatment. Venous blood samples were taken during the last 5 min of treatment from veins in the dorsum of the control and experimental feet and were later analyzed for NO concentration. Contrary to the popular supposition, PILT treatments actually resulted in a significantly (P < 0.05) decreased concentration of NO. Additionally, there were no significant differences between the treated and untreated feet. Since in individuals where PILT has significantly improved PPS, PILT did not stimulate an increased NO content in the blood, it appears that infrared light improves peripheral protective sensation in patients by a mechanism other than an increased NO production.

Comparison of effects of combined ACE inhibitor and low-dose thiazide diuretic with ACE inhibitor alone on insulin action in patients with hypertension and Type 2 diabetes: a double-blind crossover study.

AIMS: To establish the safety in terms of insulin sensitivity of a low dose thiazide/ACE inhibitor combination. METHODS: We examined the effects on insulin sensitivity of captopril either alone or in combination with low-dose bendroflumethiazide (1.25 mg) in 15 hypertensive Type 2 diabetic patients. Insulin action was assessed using an isoglycaemic hyperinsulinaemic clamp in a double-blind, randomised, crossover study after a 6-week placebo run-in and following two 12-week treatment periods with captopril (C) (100 mg) alone or in combination with bendroflumethiazide (CB) (1.25 mg). RESULTS: Blood pressure was lower following CB compare to C (138/83 vs. 144/85 mmHg; P < 0.05) and both were lower than baseline (153/92 mmHg; P < 0.01). CB resulted in a significant increase in fasting plasma glucose compared to C (9.6 +/- 2.6 vs. 8.5 +/- 1.6 mmol/l; P < 0.05). Exogenous glucose infusion rates required to maintain isoglycaemia during hyperinsulinaemia were lower after CB compared to C (25.1 +/- 13.3 vs. 34.2 +/- 16.8 micromol/kg/min; P < 0.01) as were isotopically determined glucose utilisation rates (29.0 +/- 12.4 vs. 36.6 +/- 17.3 micromol/kg/min; P < 0.05). There was no significant difference in fasting endogenous glucose production between treatments (CB 9.3 +/- 3.3 vs. C 8.6 +/- 1.6 micromol/kg/min), nor between suppression following insulin (CB 4.0 +/- 2.1 vs. C 4.3 +/- 3.1 micromol/kg/min). CONCLUSIONS: Combination of low-dose bendroflumethiazide with captopril lowered blood pressure but resulted in deleterious effects on insulin action compared to captopril alone.

Thrombin generation in vascular tissue.

BACKGROUND: Classically, it is thought that the vast majority of thrombin is generated on the surface of platelets, however, thrombotic events occur in patients despite treatment with potent antiplatelet agents. METHODS AND RESULTS: In freshly harvested left internal mammary artery (IMA) sections, addition of CaCl2 and platelet-poor plasma (PPP) were sufficient to stimulate a profound burst of thrombin and this effect was inhibited by antitissue factor antibodies. Ultracentrifugation of PPP to remove platelet microparticles had no effect on thrombin generation. Both the extrinsic and factor VIII-dependent pathways were necessary for IMA-supported thrombin generation as PPP derived from individuals deficient in factors V, VII, VIII or X did not support thrombin production. Small amounts of thrombin were generated utilizing factor IX (FIX)-deficient plasma, however, thrombin was not generated by aorta from FIX-deficient mice when FIX-deficient plasma was used. The addition of non-lipidated tissue factor (0.6 pM) and CaCl2 to actively proliferating cultured human aortic smooth muscle cells (SMC) resulted in a pronounced burst of thrombin generation occurring between 3 and 15 min after treatment. In the absence of tissue factor, thrombin was generated but at a slower rate and with a peak value 26% of that observed in the presence of tissue factor. CONCLUSION: Significant thrombin generation can occur on vascular tissue in the absence of platelets or platelet microparticles and on the surface of non-apoptotic SMC.

Ankle arthrodesis and its relationship to ipsilateral arthritis of the hind- and mid-foot.

It has been suggested that arthrodesis of the ankle leads to osteoarthritis of the joints of the ipsilateral hind- and midfoot. We believe these studies overlooked the presence of osteoarthritic changes in these joints before the arthrodesis. We reviewed the pre-operative radiographs of 70 patients with osteoarthritis of the ankle who underwent 71 ankle arthrodeses (one was bilateral). The talonavicular, calcaneocuboid, subtalar and naviculocuneiform joints were given an osteoarthritis score according to Kellgren and Lawrence. The mean age at operation was 54.9 years and the most common indication was for post-traumatic osteoarthritis (52 cases). A total of 68 patients showed pre-existing arthritis in either the hind- or mid-foot, with the subtalar joint the most commonly affected. Ipsilateral hind- and mid-foot arthritis is almost universally present in patients with arthritis of the ankle requiring arthrodesis. The presence of such changes may not be a consequence of this arthrodesis.

The effect of manipulation of basal pulsatile insulin on insulin action in Type 2 diabetes.

AIM: Disordered insulin pulsatility is associated with insulin resistant states including Type 2 diabetes. However, whether abnormal basal insulin pulses play a role in the pathogenesis of insulin resistance or are simply an associated feature remains undetermined. We investigated this relationship further by studying the effect of overnight (10 h) pulsatile insulin infusion on subsequent insulin sensitivity. METHODS: We studied 17 Type 2 diabetic patients who underwent one of two protocols. In protocol A (10 patients) on two separate nights we infused insulin 0.1 mU/kg/min either in a constant infusion or in pulses every 13 min. Octreotide (0.43 microg/kg/h) was given to suppress endogenous insulin secretion and physiological replacement of glucagon (30 ng/kg/h) administered. Insulin sensitivity was measured using a hyperinsulinaemic euglycaemic clamp (2 mU/kg/min) next morning. In protocol B (seven patients), we employed the same experimental procedure but used a basal insulin infusion rate of 0.09 mU/kg/min in 7-min or 13-min pulses. RESULTS: Appropriate pulse patterns were confirmed in each protocol. In protocol A, after overnight infusions, glucose infusion rates required to maintain euglycaemia at steady state hyperinsulinaemia were similar (33.9 +/- 5.2 vs. 31.2 +/- 4.1 micromol/kg/min; P = NS). In protocol B, after overnight infusions the glucose infusion rates required during hyperinsulinaemia were significantly lower during 7-min pulses (39.9 +/- 5.7 vs. 44.7 +/- 5.6 micromol/kg/min; P < 0.05). CONCLUSION: There was no demonstrable priming effect derived from overnight pulsatile insulin compared with constant insulin infusion on subsequent insulin sensitivity in Type 2 diabetic subjects. The failure of 7-min pulses to exhibit an advantageous effect over 13-min pulses raises questions about the natural frequency of basal insulin pulses and their biological effect.