Actions to improve quality: results from a national hospital survey.

OBJECTIVES: CMS measures and reports hospital performance to drive quality improvement (QI), but information on actions that hospitals have taken in response to quality measurement is lacking. We aimed to develop national estimates of QI actions undertaken by hospitals and to explore their relationship to performance on CMS quality measures. STUDY DESIGN: Nationally representative cross-sectional survey of acute care hospitals in 2016 (n = 1313 respondents; 64% response rate). METHODS: We assessed 23 possible QI changes. Using multivariate linear regression, we estimated the relationship between reported QI changes and performance on composite measures derived from 26 Hospital Inpatient Quality Reporting Program measures (scaled 0-100), controlling for case mix and facility characteristics. RESULTS: Hospitals reported implementing a mean of 17 QI changes (median [interquartile range], 17 [15-20]). Large hospitals reported significantly higher adoption rates than small hospitals for 18 QI changes. Most hospitals that reported making QI changes (63%-96% for the 23 changes) responded that the specific change made helped improve performance. In multivariate regression analyses, adoption of 92% of QI changes (90th percentile among hospitals), compared with adoption of 50% of QI changes (10th percentile), was associated with a 2.3-point higher overall performance score (95% CI, 0.7-4.0) and higher process (8.7 points; 95% CI, 5.7-11.7) and patient experience (3.0 points; 95% CI, 0.1-5.9) composite scores. CONCLUSIONS: Hospitals reported widespread adoption of QI changes in response to CMS quality measurement and reporting. Higher QI adoption rates were associated with modestly higher process, patient experience, and overall performance composite scores.

Insulin signaling and insulin sensitizing in muscle and liver of obese monkeys: peroxisome proliferator-activated receptor gamma agonist improves defective activation of atypical protein kinase C.

Obesity, the metabolic syndrome, and aging share several pathogenic features in both humans and non-human primates, including insulin resistance and inflammation. Since muscle and liver are considered key integrators of metabolism, we sought to determine in biopsies from lean and obese aging rhesus monkeys the nature of defects in insulin activation and, further, the potential for mitigation of such defects by an in vivo insulin sensitizer, rosiglitazone, and a thiazolidinedione activator of the peroxisome proliferator-activated receptor gamma. The peroxisome proliferator-activated receptor gamma agonist reduced hyperinsulinemia, improved insulin sensitivity, lowered plasma triglycerides and free fatty acids, and increased plasma adiponectin. In muscle of obese monkeys, previously shown to exhibit defective insulin signaling, the insulin sensitizer improved insulin activation of atypical protein kinase C (aPKC), the defective direct activation of aPKC by phosphatidylinositol (PI)-3,4,5-(PO4)3, and 5'-AMP-activated protein kinase and increased carnitine palmitoyltransferase-1 mRNA expression, but it did not improve insulin activation of insulin receptor substrate (IRS)-1-dependent PI 3-kinase (IRS-1/PI3K), protein kinase B, or glycogen synthase. We found that, although insulin signaling was impaired in muscle, insulin activation of IRS-1/PI3K, IRS-2/PI3K, protein kinase B, and aPKC was largely intact in liver and that rosiglitazone improved insulin signaling to aPKC in muscle by improving responsiveness to PI-3,4,5-(PO4)3.

Differential hypertrophy and atrophy among all types of cutaneous innervation in the glabrous skin of the monkey hand during aging and naturally occurring type 2 diabetes.

Diabetic neuropathy (DN) is a common severe complication of type 2 diabetes. The symptoms of chronic pain, tingling, and numbness are generally attributed to small fiber dysfunction. However, little is known about the pathology among innervation to distal extremities, where symptoms start earliest and are most severe, and where the innervation density is the highest and includes a wide variety of large fiber sensory endings. Our study assessed the immunochemistry, morphology, and density of the nonvascular innervation in glabrous skin from the hands of aged nondiabetic rhesus monkeys and from age-matched monkeys that had different durations of spontaneously occurring type 2 diabetes. Age-related reductions occurred among all types of innervation, with epidermal C-fiber endings preferentially diminishing earlier than presumptive Adelta-fiber endings. In diabetic monkeys epidermal innervation density diminished faster, became more unevenly distributed, and lost immunodetectable expression of calcitonin gene-related peptide and capsaicin receptors, TrpV1. Pacinian corpuscles also deteriorated. However, during the first few years of hyperglycemia, a surprising hypertrophy occurred among terminal arbors of remaining epidermal endings. Hypertrophy also occurred among Meissner corpuscles and Merkel endings supplied by Abeta fibers. After longer-term hyperglycemia, Meissner corpuscle hypertrophy declined but the number of corpuscles remained higher than in age-matched nondiabetics. However, the diabetic Meissner corpuscles had an abnormal structure and immunochemistry. In contrast, the expanded Merkel innervation was reduced to age-matched nondiabetic levels. These results indicate that transient phases of substantial innervation remodeling occur during the progression of diabetes, with differential increases and decreases occurring among the varieties of innervation.

Skeletal muscle glycogen synthase subcellular localization: effects of insulin and PPAR-alpha agonist (K-111) administration in rhesus monkeys.

Insulin covalently and allosterically regulates glycogen synthase (GS) and may also cause the translocation of GS from glycogen-poor to glycogen-rich locations. We examined the possible role of subcellular localization of GS and glycogen in insulin activation of GS in skeletal muscle of six obese monkeys and determined whether 1) insulin stimulation during a hyperinsulinemic euglycemic clamp and/or peroxisome proliferator-activated receptor (PPAR)-alpha agonist treatment (K-111, 3 mg.kg(-1).day(-1); Kowa) induced translocation of GS and 2) translocation of GS was associated with insulin activation of GS. GS and glycogen were present in all fractions obtained by differential centrifugation, except for the cytosolic fraction, under both basal and insulin-stimulated conditions. We found no evidence for translocation of GS by insulin. GS total (GST) activity was strongly associated with glycogen content (r = 0.70, P < 0.001). Six weeks of treatment with K-111 increased GST activity in all fractions, except the cytosolic fraction, and mean GST activity, GS independent activity, and glycogen content were significantly higher in the insulin-stimulated samples compared with basal samples, effects not seen with vehicle. The increase in GST activity was strongly related to the increase in glycogen content during the hyperinsulinemic euglycemic clamp after K-111 administration (r = 0.74, P < 0.001). Neither GS protein expression nor GS gene expression was affected by insulin or by K-111 treatment. We conclude that 1) in vivo insulin does not cause translocation of GS from a glycogen-poor to a glycogen-rich location in primate skeletal muscle and 2) the mechanism of action of K-111 to improve insulin sensitivity includes an increase in GST activity without an increase in GS gene or protein expression.

Minimally invasive surgery via laparoscopy for intra-abdominal biopsy in obese rhesus macaques (Macaca mulatta).

PURPOSE: To determine the safety and effectiveness of laparoscopy for repeated intra-abdominal biopsy of liver and omental adipose tissue (AT) in obese rhesus monkeys (Macaca mulatta). METHODS: Nine obese rhesus monkeys were studied by use of 18 laparoscopic procedures (two procedures each, approx. six weeks apart). Time-sensitive liver and omental AT specimens were obtained from monkeys under general anesthesia, using a three-port approach with a roticulating endoscopic stapler/divider and a monopolar electrosurgery for hemostasis. RESULTS: All subjects tolerated the initial and repeat laparoscopic procedures well. Liver specimens weighed a mean +/- SEM of 3.8 +/- 0.5 g, and omental AT specimens weighed 16.6 +/- 0.8 g. Compared with previous studies of conventional laparotomy with liver wedge resection, the monkeys experienced faster postoperative recovery via laparoscopy, with rapid return to normal food intake and activity. Minimal to no adhesions were observed by use of the repeat procedure in all monkeys, with no major complications. CONCLUSIONS: Laparoscopy in obese rhesus monkey (ranging from young to older-aged), with repeated intra-abdominal liver and omental AT biopsy, was an excellent minimally invasive surgical method. In contrast to laparotomy with wedge resection, this approach greatly decreases operative time and stress, provides generous tissue specimens in a time-efficient manner, and facilitates rapid and full recovery of the nonhuman primate.

Mortality and morbidity in laboratory-maintained Rhesus monkeys and effects of long-term dietary restriction.

Mortality and morbidity were examined in 117 laboratory-maintained rhesus monkeys studied over approximately 25 years (8 dietary-restricted [DR] and 109 ad libitum-fed [AL] monkeys). During the study, 49 AL monkeys and 3 DR monkeys died. Compared with the DR monkeys, the AL monkeys had a 2.6-fold increased risk of death. Hyperinsulinemia led to a 3.7-fold increased risk of death (p <.05); concordantly, the risk of death decreased by 7%, per unit increase in insulin sensitivity (M). There was significant organ pathology in the AL at death. The age at median survival in the AL was approximately 25 years compared with 32 years in the DR. The oldest monkey was a diabetic female (AL) that lived to be 40 years of age. These results suggest that dietary restriction leads to an increased average age of death in primates, associated with the prevention of hyperinsulinemia and the mitigation of age-related disease.

Glomerular hypertrophy is associated with hyperinsulinemia and precedes overt diabetes in aging rhesus monkeys.

BACKGROUND: Rhesus monkeys have a high prevalence of obesity and spontaneous type 2 diabetes mellitus after the age of 10 years. These monkeys go through a defined, sequential set of metabolic phases, including fasting hyperinsulinemia, impaired glucose tolerance, and fasting hyperglycemia. Using these monkeys, we addressed the hypothesis that renal structural features characteristic of diabetic nephropathy might precede the appearance of overt diabetes. METHODS: We carried out a quantitative analysis of renal tissue, using light microscopy and electron microscopy, from 6 metabolically normal young monkeys, 7 metabolically normal aged monkeys, 7 hyperinsulinemic monkeys, and 18 diabetic monkeys. RESULTS: Glomerular volume was increased significantly in hyperinsulinemic monkeys and diabetic monkeys compared with aged normal monkeys. In the normal monkey, glomerular basement membrane (GBM) width rises with age but reaches a plateau at about 20 years of age; the presence of diabetes was associated with markedly increased GBM width. Glomerular tuft volume and GBM width were correlated most closely with age and with glucose tolerance. CONCLUSION: Diabetic monkey kidneys are characterized by glomerular enlargement, glomerulosclerosis, and thickening of the GBM. Glomerular hypertrophy begins in the prediabetic hyperinsulinemic phase. This finding suggests that early intervention may be required in human patients to preserve normal glomerular structure.