Peter Homel

Outcome of Critically Ill Human Immunodeficiency Virus-Infected Patients in the Era of Highly Active Antiretroviral Therapy

The purpose of this study was to determine the effect of prior use of highly active antiretroviral therapy (HAART) on outcome of human immunodeficiency virus (HIV)- patients admitted to intensive care units (ICUs). This study was a retrospective chart review of 242 HIV-infected patients who required 259 consecutive admissions to a university-affiliated hospital ICU during a 3-year period. Patient demographics, CD4 count, admission diagnosis, prior HAART, Pneumocystis jiroveci prophylaxis, length of stay, and ICU and hospital mortality were determined. Overall hospital mortality was 39%. Comparing patients who had received HAART before an ICU admission to those who had not, we found no difference between ICU or hospital mortality, need of mechanical ventilation, ICU and hospital length of stay, and incidence of P jiroveci . Pulmonary diagnosis was the most frequent ICU admission diagnosis (30%). Logistic regression analysis showed HIV-related illness and mechanical ventilation were significant independent predictors of increased hospital mortality.

Limited recovery of β-cell function after gastric bypass despite clinical diabetes remission.

The mechanisms responsible for the remarkable remission of type 2 diabetes after Roux-en-Y gastric bypass (RYGBP) are still puzzling. To elucidate the role of the gut, we compared β-cell function assessed during an oral glucose tolerance test (OGTT) and an isoglycemic intravenous glucose clamp (iso-IVGC) in: 1) 16 severely obese patients with type 2 diabetes, up to 3 years post-RYGBP; 2) 11 severely obese normal glucose-tolerant control subjects; and 3) 7 lean control subjects. Diabetes remission was observed after RYGBP. β-Cell function during the OGTT, significantly blunted prior to RYGBP, normalized to levels of both control groups after RYGBP. In contrast, during the iso-IVGC, β-cell function improved minimally and remained significantly impaired compared with lean control subjects up to 3 years post-RYGBP. Presurgery, β-cell function, weight loss, and glucagon-like peptide 1 response were all predictors of postsurgery β-cell function, although weight loss appeared to be the strongest predictor. These data show that β-cell dysfunction persists after RYGBP, even in patients in clinical diabetes remission. This impairment can be rescued by oral glucose stimulation, suggesting that RYGBP leads to an important gastrointestinal effect, critical for improved β-cell function after surgery.

Intravenous Subdissociative-Dose Ketamine Versus Morphine for Analgesia in the Emergency Department: A Randomized Controlled Trial.

STUDY OBJECTIVE We assess and compare the analgesic efficacy and safety of subdissociative intravenous-dose ketamine with morphine in emergency department (ED) patients. METHODS This was a prospective, randomized, double-blind trial evaluating ED patients aged 18 to 55 years and experiencing moderate to severe acute abdominal, flank, or musculoskeletal pain, defined as a numeric rating scale score greater than or equal to 5. Patients were randomized to receive ketamine at 0.3 mg/kg or morphine at 0.1 mg/kg by intravenous push during 3 to 5 minutes. Evaluations occurred at 15, 30, 60, 90, and 120 minutes. Primary outcome was reduction in pain at 30 minutes. Secondary outcome was the incidence of rescue analgesia at 30 and 60 minutes. RESULTS Forty-five patients per group were enrolled in the study. The primary change in mean pain scores was not significantly different in the ketamine and morphine groups: 8.6 versus 8.5 at baseline (mean difference 0.1; 95% confidence interval -0.46 to 0.77) and 4.1 versus 3.9 at 30 minutes (mean difference 0.2; 95% confidence interval -1.19 to 1.46; P=.97). There was no difference in the incidence of rescue fentanyl analgesia at 30 or 60 minutes. No statistically significant or clinically concerning changes in vital signs were observed. No serious adverse events occurred in either group. Patients in the ketamine group reported increased minor adverse effects at 15 minutes post-drug administration. CONCLUSION Subdissociative intravenous ketamine administered at 0.3 mg/kg provides analgesic effectiveness and apparent safety comparable to that of intravenous morphine for short-term treatment of acute pain in the ED.

Risk factors for pelvic inflammatory disease in inner-city adolescents.

Objective: To determine risk factors associated with pelvic inflammatory disease (PID) among inner‐city adolescents. Study Design: A case‐control study was performed from 1994 to 1997 in an inner‐city hospital. Methods: Seventy‐one adolescent girls diagnosed with PID and 52 sexually active adolescents girls without PID participated in a confidential face‐to‐face interview using a questionnaire about risk behaviors. Established criteria were used for the diagnosis of PID. Data were analyzed using t tests, chi‐square tests, and stepwise logistic regression. Results: Persons with PID were significantly more likely to show younger age at first intercourse, older sex partners, involvement with a child protection agency, prior suicide attempt(s), consumption of alcohol before last sex, and a current Chlamydia trachomatis infection. There were no significant differences between the two groups regarding number of lifetime sex partners, condom use, rape, syphilis, prior PID, hepatitis B, hepatitis C, or HIV infection. Conclusions: Not previously noted in the literature are the association of PID with older sex partners, prior involvement in a child protection agency, and a prior suicide attempt. Confirming prior studies are the association of PID with earlier age at first sex, alcohol use, and C trachomatis infection.

Magnitude and variability of the glucagon-like peptide-1 response in patients with type 2 diabetes up to 2 years following gastric bypass surgery.

OBJECTIVE To characterize the magnitude and variance of the change of glucose and glucagon-like peptide-1 (GLP-1) concentrations, and to identify determinants of glucose control up to 2 years after gastric bypass (GBP). RESEARCH DESIGN AND METHODS Glucose and GLP-1 concentrations were measured during an oral glucose challenge before and 1, 12, and 24 months after GBP in 15 severely obese patients with type 2 diabetes. RESULTS Glucose area under the curve from 0 to 180 min (AUC0–180) started decreasing in magnitude (P < 0.05) 1 month after surgery. GLP-1 AUC0–180 increased in magnitude 1 month after GBP (P < 0.05), with increased variance only after 1 year (Pσ2 ≤ 0.001). GLP-1 AUC0–180 was positively associated with insulin AUC0–180 (P = 0.025). CONCLUSIONS The increase in variance of GLP-1 at 1 and 2 years after GBP suggests mechanisms other than proximal gut bypass to explain the enhancement of GLP-1 secretion. The association between GLP-1 and insulin concentrations supports the idea that the incretins are involved in glucose control after GBP.

Efficacy of deep venous thrombosis prophylaxis in the medical intensive care unit.

The purpose of this study was to determine the incidence of deep venous thrombosis in medical intensive care unit patients receiving deep venous thrombosis prophylaxis. This was a prospective cohort study of 141 consecutive adult patients anticipated to remain in the medical intensive care unit for >48 hours. Deep venous thrombosis prophylaxis was provided using subcutaneous unfractionated heparin or a sequential compression device according to risk-stratified protocol. Compression ultrasound was performed. Fourteen patients (9.9%) developed deep venous thrombosis on follow-up studies. Incidence of deep venous thrombosis was 7.9% per person year (95% confidence interval, 4.8-12.8). Two of 14 developed pulmonary embolism. Eight patients required full anticoagulation with intravenous heparin or coumadin. In-hospital mortality was similar in both groups. Patients with deep venous thrombosis had a statistically higher risk of pulmonary embolism: 14.2% (95% confidence interval, 2.0-43.0) versus 0.0% (95% confidence interval, 0-3; P = .009). Incidence of deep venous thrombosis is high in medical intensive care unit patients receiving standard prophylaxis. Adherence to strict deep venous thrombosis prophylaxis protocol and exploration of other prophylaxis regimens should be pursued.

Randomized study of early intravenous esmolol versus oral beta-blockers in preventing post-CABG atrial fibrillation in high risk patients identified by signal-averaged ECG: results of a pilot study.

Background: Patients with prolonged signal‐averaged ECG have four times higher risk for development of atrial fibrillation (AF) after coronary artery bypass surgery (CABG). Incidence of AF is reduced, but not eliminated by prophylaxis with beta‐blockers. The limitations of prophylaxis with oral beta‐blockers may be related to the delayed effect of oral therapy. We performed a pilot study of the efficacy of early intravenous esmolol and an oral beta‐blocker regimen for prevention of postoperative AF.

A prospective randomized, double-dummy trial comparing intravenous push dose of low dose ketamine to short infusion of low dose ketamine for treatment of moderate to severe pain in the emergency department

Study objective Compare adverse effects and analgesic efficacy of low‐dose ketamine for acute pain in the ED administered either by single intravenous push (IVP) or short infusion (SI). Methods Patients 18–65, presenting to ED with acute abdominal, flank, or musculoskeletal pain with initial pain score ≥ 5, were randomized to ketamine 0.3 mg/kg by either IVP or SI with placebo double‐dummy. Adverse effects were evaluated by Side Effects Rating Scale for Dissociative Anesthetics (SERSDA) and Richmond Agitation‐Sedation Scale (RASS) at 5, 15, 30, 60, 90, and 120 min post‐administration; analgesic efficacy was evaluated by Numerical Rating Scale (NRS). Results 48 patients enrolled in the study. IVP group had higher overall rates of feeling of unreality on SERSDA scale: 92% versus 54% (difference 37.5%; p = 0.008; 95% CI 9.3–59.5%). At 5 min median severity of feeling of unreality was 3.0 for IVP versus 0.0 for SI (p = 0.001). IVP also showed greater rates of sedation on RASS scale at 5 min: median RASS − 2.0 versus 0.0 (p = 0.01). Decrease in mean pain scores from baseline to 15 min was similar across groups: 5.2 ± 3.53 (95% CI 3.7–6.7) for IVP; 5.75 ± 3.48 (95% CI 4.3–7.2) for SI. There were no statistically significant differences with respect to changes in vital signs and need for rescue medication. Conclusion Low‐dose ketamine given as a short infusion is associated with significantly lower rates of feeling of unreality and sedation with no difference in analgesic efficacy in comparison to intravenous push.

Comparison of Intravenous Ketorolac at Three Single-Dose Regimens for Treating Acute Pain in the Emergency Department: A Randomized Controlled Trial.

Study objective Nonsteroidal anti‐inflammatory drugs are used extensively for the management of acute and chronic pain, with ketorolac tromethamine being one of the most frequently used parenteral analgesics in the emergency department (ED). The drugs may commonly be used at doses above their analgesic ceiling, offering no incremental analgesic advantage while potentially adding risk of harm. We evaluate the analgesic efficacy of 3 doses of intravenous ketorolac in ED patients with acute pain. Methods We conducted a randomized, double‐blind trial to assess the analgesic efficacy of 3 doses of intravenous ketorolac (10, 15, and 30 mg) in patients aged 18 to 65 years and presenting to the ED with moderate to severe acute pain, defined by a numeric rating scale score greater than or equal to 5. We excluded patients with peptic ulcer disease, gastrointestinal hemorrhage, renal or hepatic insufficiency, allergies to nonsteroidal anti‐inflammatory drugs, pregnancy or breastfeeding, systolic blood pressure less than 90 or greater than 180 mm Hg, and pulse rate less than 50 or greater than 150 beats/min. Primary outcome was pain reduction at 30 minutes. We recorded pain scores at baseline and up to 120 minutes. Intravenous morphine 0.1 mg/kg was administered as a rescue analgesic if subjects still desired additional pain medication at 30 minutes after the study drug was administered. Data analyses included mixed‐model regression and ANOVA. Results We enrolled 240 subjects (80 in each dose group). At 30 minutes, substantial pain reduction was demonstrated without any differences between the groups (95% confidence intervals 4.5 to 5.7 for the 10‐mg group, 4.5 to 5.6 for the 15‐mg group, and 4.2 to 5.4 for the 30‐mg group). The mean numeric rating scale pain scores at baseline were 7.7, 7.5, and 7.8 and improved to 5.1, 5.0, and 4.8, respectively, at 30 minutes. Rates of rescue analgesia were similar, and there were no serious adverse events. Secondary outcomes showed similar rates of adverse effects per group, of which the most common were dizziness, nausea, and headache. Conclusion Ketorolac has similar analgesic efficacy at intravenous doses of 10, 15, and 30 mg, showing that intravenous ketorolac administered at the analgesic ceiling dose (10 mg) provided effective pain relief to ED patients with moderate to severe pain without increased adverse effects.

Children neglected: Where cumulative risk theory fails

Neglected children, by far the majority of children maltreated, experience an environment most deficient in cognitive stimulation and language exchange. When physical abuse co-occurs with neglect, there is more stimulation through negative parent-child interaction, which may lead to better cognitive outcomes, contrary to Cumulative Risk Theory. The purpose of the current study was to assess whether children only neglected perform worse on cognitive tasks than children neglected and physically abused. Utilizing LONGSCAN archived data, 271 children only neglected and 101 children neglected and physically abused in the first four years of life were compared. The two groups were assessed at age 6 on the WPPSI-R vocabulary and block design subtests, correlates of cognitive intelligence. Regression analyses were performed, controlling for additional predictors of poor cognitive outcome, including socioeconomic variables and caregiver depression. Children only neglected scored significantly worse than children neglected and abused on the WPPSI-R vocabulary subtest (p=0.03). The groups did not differ on the block design subtest (p=0.4). This study shows that for neglected children, additional abuse may not additively accumulate risk when considering intelligence outcomes. Children experiencing only neglect may need to be referred for services that address cognitive development, with emphasis on the linguistic environment, in order to best support the developmental challenges of neglected children.