Impact of 4 + 1 block scheduling on patient care continuity in resident clinic.

BACKGROUND: Leaders in medical education have called for redesign of internal medicine training to improve ambulatory care training. 4 + 1 block scheduling is one innovative approach to enhance ambulatory education. AIM: To determine the impact of 4 + 1 scheduling on resident clinic continuity. SETTING: Resident continuity clinic in traditional scheduling in which clinics are scheduled intermittently one-half day per week, compared to 4 + 1 in which residents alternate 1 week of clinic with 4 weeks of an inpatient rotation or elective. PARTICIPANTS: First-year internal medicine residents. PROGRAM DESCRIPTION: We measured patient-provider visit continuity, phone triage encounter continuity, and lab follow-up continuity. PROGRAM EVALUATION: In traditional scheduling as opposed to 4 + 1 scheduling, patients saw their primary resident provider a greater percentage; 71.7% vs. 63.0% (p = 0.008). In the 4 + 1 model, residents saw their own patients a greater percentage; 52.1% vs. 37.1% (p = 0.0001). Residents addressed their own labs more often in 4 + 1 model; 90.7% vs. 75.6% (p = 0.001). There was no significant difference in handling of triage encounters; 42.3% vs. 35.8% (p = 0.12). DISCUSSION: 4 + 1 schedule improves visit continuity from a resident perspective, and may compromise visit continuity from the patient perspective, but allows for improved laboratory follow-up, which we pose should be part of an emerging modern definition of continuity.

Recombinant methionyl human leptin administration activates signal transducer and activator of transcription 3 signaling in peripheral blood mononuclear cells in vivo and regulates soluble tumor necrosis factor-alpha receptor levels in humans with relative leptin deficiency.

Studies of congenital complete leptin deficiency in animals and humans support a role for leptin in regulating immune function. Whether acquired relative leptin deficiency affects immunological parameters in healthy humans remains unknown. We thus used experimental models of relative leptin deficiency and recombinant methionyl human leptin (r-metHuLeptin) administration in humans to investigate whether r-metHuLeptin would activate signaling pathways in peripheral blood mononuclear cells (PBMCs) and whether acquired relative leptin deficiency and/or increasing circulating leptin levels into the physiologic range would change PBMC subpopulations and cytokines important in the T-helper cell and systemic immune responses. We found that r-metHuLeptin administration to healthy humans activates signal transducer and activator of transcription-3 signaling in PBMCs in vivo. Neither short-term leptin deficiency, induced by 3-d complete fasting, nor physiologic r-metHuLeptin replacement for the same period of time had a major effect on PBMC subpopulations or serum cytokines in healthy men. In contrast, normalizing serum leptin levels over 8 wk in lean women with relative leptin deficiency for 5.1 +/- 1.4 yr (mean +/- se) due to chronic energy deficit increased soluble TNFalpha receptor levels, indicating activation of the TNFalpha system. These findings suggest that relative leptin deficiency due to more long-term energy deprivation is associated with defects in immunological parameters that may be corrected with exogenous r-metHuLeptin administration. Further studies are warranted to assess the implications of acquired relative hypoleptinemia and/or r-metHuLeptin administration on the immunosuppression associated with energy- and leptin-deficient states in humans.

Circulating melanin-concentrating hormone, agouti-related protein, and alpha-melanocyte-stimulating hormone levels in relation to body composition: alterations in response to food deprivation and recombinant human leptin administration.

We evaluated whether circulating levels of melanin-concentrating hormone (MCH), agouti-related protein (AGRP), and alpha-MSH could serve as useful markers of energy homeostasis in humans. We first assessed correlations of serum MCH, AGRP, and alpha-MSH with anthropometric, dietary, and hormonal variables in a cross-sectional study of 108 healthy humans. We then performed interventional studies to evaluate the effects of fasting and/or leptin administration. In eight healthy, normal weight men, we measured serum MCH, AGRP, and alpha-MSH levels at baseline, after 2 d of fasting alone (a low leptin state), and after 2 d of fasting with replacement dose recombinant methionyl human leptin (r-metHuLeptin) administration to normalize circulating leptin levels. In a separate group of five lean and five obese men, we measured MCH levels in response to increasing circulating leptin levels to the pharmacological range by administration of one r-metHuLeptin dose in the fed state. In the cross-sectional study, serum MCH levels were independently and positively associated with body mass index and fat mass and were higher in women than in men. Furthermore, in our interventional studies, fasting for 2 d significantly decreased leptin levels and increased serum MCH levels. Administration of replacement dose r-metHuLeptin during fasting prevented the fasting-induced increase in MCH levels, but administration of a pharmacological r-metHuLeptin dose in the fed state did not further alter MCH levels. Serum AGRP levels tended to change in directions similar to MCH, but this change was less pronounced and needs to be investigated in larger studies. In contrast, serum alpha-MSH levels did not correlate with body composition parameters, were not associated with caloric or macronutrient intake, and were not significantly affected by fasting or r-metHuLeptin administration. These findings suggest that serum MCH and possibly AGRP levels could serve as useful peripheral markers of changes in energy homeostasis and thus merit additional investigation.

The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men.

To elucidate the role of leptin in regulating neuroendocrine and metabolic function during an acute fast, six to eight healthy, lean men were studied under four separate conditions: a baseline fed state and three 72-hour fasting studies with administration of either placebo, low-dose recombinant-methionyl human leptin (r-metHuLeptin), or replacement-dose r-metHuLeptin designed to maintain serum leptin at levels similar to those in the fed state. Replacement-dose r-metHuLeptin administered during fasting prevents the starvation-induced changes in the hypothalamic-pituitary-gonadal axis and, in part, the hypothalamic-pituitary-thyroid axis and IGF-1 binding capacity in serum. Thus, in normal men, the fall in leptin with fasting may be both necessary and sufficient for the physiologic adaptations of these axes, which require leptin levels above a certain threshold for activation. In contrast to findings in mice, fasting-induced changes in the hypothalamic-pituitary-adrenal, renin-aldosterone, and growth hormone-IGF-1 axes as well as fuel utilization may be independent of leptin in humans. The role of leptin in normalizing several starvation-induced neuroendocrine changes may have important implications for the pathophysiology and treatment of eating disorders and obesity.

Leptin and soluble leptin receptor in follicular fluid.

PURPOSE: Previous studies suggest that follicular fluid leptin levels predict successful assisted reproduction. The relationship between intrafollicular leptin and the soluble leptin receptor, ovarian hormones, and oocyte quality was examined to determine potential factors contributing to this finding. METHODS: Follicular fluid leptin, soluble leptin receptor, hormones, and oocyte quality were examined in 84 individual follicles from 30 women undergoing in vitro fertilization. RESULTS: Follicular fluid leptin and soluble leptin receptor levels correlated inversely with each other (r = -0.354; p = 0.001). Follicular fluid leptin levels correlated with intrafollicular estradiol (r = 0.42; p < 0.001), progesterone (r = 0.48; p < 0.001), and androstenedione (r = 0.49; p < 0.001), whereas soluble leptin receptor levels correlated with activin (r = 0.38; p < 0.001) and follistatin (r = 0.35; p < 0.002). There was no relationship between follicular fluid leptin or soluble leptin receptor levels and pretreatment serum hormone levels, stimulated serum estradiol, follicle number, oocyte quality, fertilization, or embryo grade. CONCLUSION: The data demonstrate that leptin and the soluble leptin receptor are highly interrelated with each other and with other intrafollicular hormones, but not with markers of oocyte quality, fertilization, or embryo grade.