Paul Kelly

OBJECTIVE: To determine the incidence, predisposing factors, and costs of emergency treatment of severe hypoglycemia in people with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS: Over a 12-month period, routinely collected datasets were analyzed in a population of 367,051 people, including 8,655 people with diabetes, to measure the incidence of severe hypoglycemia that required emergency assistance from Ninewells Hospital and Medical School (NHS) personnel including those in primary care, ambulance services, hospital accident and emergency departments, and inpatient care. Associated costs with these episodes were calculated. RESULTS: A total of 244 episodes of severe hypoglycemia were recorded in 160 patients, comprising 69 (7.1%) people with type 1 diabetes, 66 (7.3%) with type 2 diabetes treated with insulin, and 23 (0.8%) with type 2 diabetes treated with sulfonylurea tablets. Incidence rates were 11.5 and 11.8 events per 100 patient-years for type 1 and type 2 patients treated with insulin, respectively. Age, duration, and socioeconomic status were identified as risk factors for severe hypoglycemia. One in three cases were treated solely by the ambulance service with no other contact from health care professionals. The total estimated cost of emergency treatment of severe hypoglycemia was </= pound 92,078 in one year. CONCLUSIONS: Hypoglycemia requiring emergency assistance from health service personnel is as common in people with type 2 diabetes treated with insulin as in people with type 1 diabetes. It is associated with considerable NHS resource use that has a significant economic and personal cost.

BACKGROUND: Prolonged corticosteroid therapy increases the risk of osteoporosis and fracture. We studied whether corticosteroid-induced osteoporosis could be prevented by treatment with calcium, calcitriol (1,25-dihydroxyvitamin D3), and calcitonin. METHODS: One hundred three patients starting long-term corticosteroid therapy were randomly assigned to receive 1000 mg of calcium per day orally and either calcitriol (0.5 to 1.0 microgram per day orally) plus salmon calcitonin (400 IU per day intranasally), calcitriol plus a placebo nasal spray, or double placebo for one year. Data on treatment efficacy were available for 92 of these patients. Bone density was measured every four months for two years by photon absorptiometry. There were no significant differences between groups with respect to age, underlying disease, initial bone density, or corticosteroid dose during the first year. RESULTS: Calcitriol (mean dose, 0.6 microgram per day), with or without calcitonin, prevented more bone loss from the lumbar spine (mean rates of change, -0.2 and -1.3 percent per year, respectively) than calcium alone (-4.3 percent per year, P = 0.0035). Bone loss at the femoral neck and distal radius was not significantly affected by any treatment. In the second year, lumbar bone loss did not occur in the group previously treated with calcitonin plus calcitriol (+0.7 percent per year), but it did occur in the group given calcium alone (-2.3 percent per year). The calcitriol group also lost lumbar bone (-3.6 percent per year) but received more corticosteroid in the second year than the other two groups. CONCLUSIONS: Calcitriol and calcium, used prophylactically with or without calcitonin, prevent corticosteroid-induced bone loss in the lumbar spine.

Importance: The effect of an early resuscitation protocol on sepsis outcomes in developing countries remains unknown. Objective: To determine whether an early resuscitation protocol with administration of intravenous fluids, vasopressors, and blood transfusion decreases mortality among Zambian adults with sepsis and hypotension compared with usual care. Design, Setting, and Participants: Randomized clinical trial of 212 adults with sepsis (suspected infection plus ≥2 systemic inflammatory response syndrome criteria) and hypotension (systolic blood pressure ≤90 mm Hg or mean arterial pressure ≤65 mm Hg) presenting to the emergency department at a 1500-bed referral hospital in Zambia between October 22, 2012, and November 11, 2013. Data collection concluded December 9, 2013. Interventions: Patients were randomized 1:1 to either (1) an early resuscitation protocol for sepsis (n = 107) that included intravenous fluid bolus administration with monitoring of jugular venous pressure, respiratory rate, and arterial oxygen saturation and treatment with vasopressors targeting mean arterial pressure (≥65 mm Hg) and blood transfusion (for patients with a hemoglobin level <7 g/dL) or (2) usual care (n = 105) in which treating clinicians determined hemodynamic management. Main Outcomes and Measures: The primary outcome was in-hospital mortality and the secondary outcomes included the volume of intravenous fluid received and receipt of vasopressors. Results: Among 212 patients randomized to receive either the sepsis protocol or usual care, 3 were ineligible and the remaining 209 completed the study and were included in the analysis (mean [SD] age, 36.7 [12.4] years; 117 men [56.0%]; 187 [89.5%] positive for the human immunodeficiency virus). The primary outcome of in-hospital mortality occurred in 51 of 106 patients (48.1%) in the sepsis protocol group compared with 34 of 103 patients (33.0%) in the usual care group (between-group difference, 15.1% [95% CI, 2.0%-28.3%]; relative risk, 1.46 [95% CI, 1.04-2.05]; P = .03). In the 6 hours after presentation to the emergency department, patients in the sepsis protocol group received a median of 3.5 L (interquartile range, 2.7-4.0 L) of intravenous fluid compared with 2.0 L (interquartile range, 1.0-2.5 L) in the usual care group (mean difference, 1.2 L [95% CI, 1.0-1.5 L]; P < .001). Fifteen patients (14.2%) in the sepsis protocol group and 2 patients (1.9%) in the usual care group received vasopressors (between-group difference, 12.3% [95% CI, 5.1%-19.4%]; P < .001). Conclusions and Relevance: Among adults with sepsis and hypotension, most of whom were positive for HIV, in a resource-limited setting, a protocol for early resuscitation with administration of intravenous fluids and vasopressors increased in-hospital mortality compared with usual care. Further studies are needed to understand the effects of administration of intravenous fluid boluses and vasopressors in patients with sepsis across different low- and middle-income clinical settings and patient populations. Trial Registration: clinicaltrials.gov Identifier: NCT01663701.