Postoperative delirium and cognitive dysfunction.

Postoperative delirium and cognitive dysfunction (POCD) are topics of special importance in the geriatric surgical population. They are separate entities, whose relationship has yet to be fully elucidated. Although not limited to geriatric patients, the incidence and impact of both are more profound in geriatric patients. Delirium has been shown to be associated with longer and more costly hospital course and higher likelihood of death within 6 months or postoperative institutionalization. POCD has been associated with increased mortality, risk of leaving the labour market prematurely, and dependency on social transfer payments. Here, we review their definitions and aetiology, and discuss treatment and prevention in elderly patients undergoing major non-cardiac surgery. Good basic care demands identification of at-risk patients, awareness of common perioperative aggravating factors, simple prevention interventions, recognition of the disease states, and basic treatments for patients with severe hyperactive manifestations.

Delirium is associated with early postoperative cognitive dysfunction.

The purpose of this analysis was to determine if postoperative delirium was associated with early postoperative cognitive dysfunction (at 7 days) and long-term postoperative cognitive dysfunction (at 3 months). The International Study of Postoperative Cognitive Dysfunction recruited 1218 subjects >or= 60 years old undergoing elective, non-cardiac surgery. Postoperatively, subjects were evaluated for delirium using the criteria of the Diagnostic and Statistical Manual. Subjects underwent neuropsychological testing pre-operatively and postoperatively at 7 days (n = 1018) and 3 months (n = 946). Postoperative cognitive dysfunction was defined as a composite Z-score > 2 across tests or at least two individual test Z-scores > 2. Subjects with delirium were significantly less likely to participate in postoperative testing. Delirium was associated with an increased incidence of early postoperative cognitive dysfunction (adjusted risk ratio 1.6, 95% CI 1.1-2.1), but not long-term postoperative cognitive dysfunction (adjusted risk ratio 1.3, 95% CI 0.6-2.4). Delirium was associated with early postoperative cognitive dysfunction, but the relationship of delirium to long-term postoperative cognitive dysfunction remains unclear.

Predictive value of gastric parietal cell autoantibodies as a marker for gastric and hematologic abnormalities associated with insulin-dependent diabetes.

The frequency and significance of gastric parietal cell autoimmunity was assessed in 771 patients with insulin-dependent diabetes (IDD) of onset before 30 yr of age. Gastric parietal autoantibodies (PCA) were found 4 times more frequently in the patients with IDD (9%) than among 600 matched nondiabetic controls (2%). Caucasian female patients with IDD had PCA twice as frequently as male patients. Thyroid microsomal autoantibodies were more frequent in patients with IDD and PCA, than in those with IDD alone (Caucasian 46% versus 18%, black 25% versus 2.5%). A history of pernicious anemia and/or PCA was found in 25 or 40 families of IDD probands with PCA. Achlorhydria was demonstrated in 6 of 11 patients (54%) with PCA but in none of seven IDD patients without PCA. The six patients with achlorhydria had significantly lower uptakes of oral radiolabeled cobalamin, lower serum cobalamin levels, lower intrinsic factor-R protein ratios in their gastric aspirates, and lower plasma ferritin levels than patients with IDD but without PCA. None of the study group had IF antibodies in their serum or gastric juice. Overt pernicious anemia and neuropathy were found in one patient with PCA. Young patients with IDD at risk for atrophic gastritis and cobalamin deficiency can initially be identified by screening for PCA. Many of these young patients with PCA already have achlorhydria and evidence of decreased absorption of cobalamin. These patients can then be followed with cobalamin levels and/or with complete blood counts to identify those requiring therapy.

Ambulatory diabetes management by a pulse of subcutaneous insulin delivered by a portable pump: preliminary report.

Two teenage patients, who had severe psychosocial problems that complicated their diabetes management, were treated for one month (14-year-old girl) and two months (16-year-old boy) by frequent pulses of insulin injected subcutaneously by a portable, programmed pump. Additional pulses were manually adjusted by the patient before eating. Both patients experienced improved sense of well-being, marked reduction in urine volume and in glycosuria, and reduced glycemic excursions and average levels. The boy had accelerated linear growth and a decreas in HbA1 percentage. Despite marked clinical improvement, permitting return to school, the girl was impelled to interrupt pump administration after two weeks. Both patients continue to use the device voluntarily; a smaller unit, however, that doesn't have the conspicuous external controls, would likely be readily acceptable to most young patients.

Limited joint mobility in childhood diabetes: family studies.

We examined 204 persons with insulin-dependent diabetes mellitus (IDDM), aged 7-23 yr, and 336 of their first-degree relatives, to determine whether there is a genetic component to the development of limited joint mobility. Simple and multiplex pedigrees with IDDM were studied along with normal controls. Only 1 of 90 normal controls had joint stiffness. Among 225 nondiabetic parents of children with IDDM, 7 (3%) had joint limitation, compared with 42 (21%) of children and youth with IDDM. Only 1 of 108 nondiabetic siblings of diabetic probands had limitation. Three parents had adult-onset diabetes and all had limited joint mobility. None of the 8 nondiabetic relatives with joint limitation had diabetic probands with joint involvement; 5 of these 8 tested were negative for islet cell auto-antibodies. There were 11 IDDM multiplex families with at least one member having joint limitation. The concordance rate for limited joint mobility of persons with diabetes for more than 5 yr who were over 12 yr of age was 56%, not different from the 48% frequency in patients with IDDM who met these age and duration criteria. Thus, evidence that limited joint mobility is a metabolic consequence of diabetes includes the virtual absence of limitation among first-degree relatives of probands, including probands with joint stiffness, and that the frequency of joint involvement is not increased in first-degree relatives of patients with IDDM. Furthermore, two brothers with pancreatic hypoplasia and a non-HLA-associated form of IDDM were affected with limited joint mobility. Nonetheless, the expression of this complication must be influenced by host factors, since not all persons with IDDM develop it, and those who do have variable ages of onset without correlation to control measures.

Offering a randomized trial of intensive therapy for IDDM to adolescents. Reasons for refusal, patient characteristics, and recruiter effects.

OBJECTIVE: To identify reasons adolescents refuse to participate in a randomized trial of intensive therapy (IT) for IDDM, to describe the patient characteristics of those who consent and those who refuse to participate, and to examine recruiter effects on trial participation rates. RESEARCH DESIGN AND METHODS: A total of 99 adolescents, age 11-18 years, were provided with the results of the Diabetes Control and Complications Trial and approached for possible study participation by two nurse recruiters. Adolescents refusing the trial were administered a semi-structured interview to describe reasons for study refusal; responses were recorded and later coded into categories. Patient characteristics of consenters and refusers were collected and compared. The differential enrollment rates of the two nurse recruiters were also compared. RESULTS: A total of 56 patients (approximately 57%) agreed to participate; 43 refused. The four most common reasons for study refusal were 1) increased clinic visits (42%), 2) increased insulin injections (30%), 3) increased frequency of self-monitoring of blood glucose (SMBG) (28%), and 4) transportation difficulties (19%). Concerns about randomization to an unwanted treatment condition and fears of hypoglycemia or weight gain were rarely cited. Consenters and refusers did not differ in demographic characteristics, disease status, or family composition. Large differences were found between the two nurse recruiters: one experienced a 60% refusal rate, while the other experienced a 27% refusal rate. CONCLUSIONS: Issues of convenience (increased clinic visits, transportation difficulties) and concerns about the demands of IT (increased injections and SMBG) were the predominant reasons for trial refusal. Patient characteristics did not differentiate consenters from refusers. However, recruiters differed greatly in study refusal rates, suggesting that provider behavior may be an important but understudied aspect of adolescent acceptance of randomized trials in general and IT in particular.

Accuracy of two systems for blood glucose monitoring without a meter (Chemstrip/Visidex).

Blood specimens collected from 159 campers were tested using Visidex (VD) (Ames Company, Elkhart, Indiana) and Chemstrip (CS) (Bio-Dynamics, Boehringer Mannheim, Indianapolis, Indiana) compared with glucose analyzer (GA) results. Readers were physicians, two with no prior experience using either strip and two with some experience using CS. Subsequently, 30 clinic patients and 4 staff contributed random specimens that were read by a trained novice as 68 discrete samples and compared with GA results. In both studies readers did not place blood on the strips and were thus blinded as to source and the possible previous reading with the other strip. Correlations of VD and CS with GA for camp and clinic data were calculated. Data were compared for reliability and errors greater than 20% of reference values (GA) were compared for VD and CS. CS correlated better with GA than did VD estimates. Reliability was also significantly greater for CS than for VD readings. Both of these visually read methods provided clinically useful estimates of glycemia.

Disordered eating, body mass, and glycemic control in adolescents with type 1 diabetes.

OBJECTIVE: To examine the relationship between disordered eating attitudes and behaviors, BMI, and glycemic control in adolescents with type 1 diabetes. RESEARCH DESIGN AND METHODS: In a cross-sectional design, 152 adolescents (ages 11-19 years) completed three scales from the Eating Disorders Inventory (EDI): Body Dissatisfaction, Drive for Thinness, and Bulimia. All subjects had diabetes for > 1 year. Glycemic control was assessed by glycosylated hemoglobin (HbA1c). Height and weight were measured to assess BMI. RESULTS: Adolescents with type 1 diabetes did not report more disordered eating attitudes and behaviors than the normative comparison sample. Male subjects with type 1 diabetes reported fewer symptoms of bulimia and female subjects with type 1 diabetes reported greater body satisfaction than the normative group. A higher BMI was a significant predictor of greater body dissatisfaction, more so for female than male subjects. Symptoms of bulimia were associated with older adolescence and female sex. Those with more symptoms of bulimia were also more likely to have a higher BMI. Sex (female) and body dissatisfaction (more dissatisfied) predicted a stronger desire to be thin. Longer duration of disease, more symptoms of bulimia, and obesity all predicted poorer glycemic control. CONCLUSIONS: Female patients aged 13-14 years seem to be at greatest risk for developing disordered eating patterns. Using the clinical cutoff score (> or = 5) of the EDI Bulimia subscale as a screener in diabetes clinics may help identify adolescents whose disordered eating patterns are likely to compromise their glycemic control.

Insulin and islet cell autoantibodies as time-dependent covariates in the development of insulin-dependent diabetes: a prospective study in relatives.

Using time-dependent methods, the temporal relationships between the detection of insulin and islet cell autoantibodies and the onset of insulin dependent diabetes (IDDM) were analyzed in a prospective study of 4694 nondiabetic relatives of 1929 patients with IDDM who had been followed for a median of 4 yr. Insulin autoantibodies were detected in 1.5% of relatives at their initial test whereas an additional 1.0% subsequently became positive for these antibodies during follow-up. Islet cell autoantibodies were detected in 2.6% of the relatives at the time of their first test and an additional 0.9% were observed to develop them during the follow-up period. The risk of developing IDDM was significantly higher (P = 0.0001) among those who were found to have one of these antibodies, but was highest among those under the age of 20 yr at inception of this study who tested positive for both. Among older relatives, the detection of insulin autoantibodies among those who were islet cell antibody positive did not convey an additional risk of IDDM. In a subset of relatives, the presence of either antibody was associated with a higher frequency (P < 0.001) of diabetes associated human leukocyte antigen-DR 3/4 heterozygotes. Islet cell autoantibodies were highly associated with elevated fasting and 60-min glucose concentrations (P = 0.0001) as well as decreased early phase (1 and 3 min) insulin response to an iv glucose tolerance test (P = 0.0001). Insulin antibodies were significantly associated with decreased early phase insulin response to iv glucose (P = 0.0003). These data confirm independent risks associated with each antibody and suggest that their temporal relationship may be an important reflection of the pathogenic process underlying IDDM observations which facilitate its predictability.

Adrenal neuropeptide Y mRNA but not preproenkephalin mRNA induction by stress is impaired by aging in Fischer 344 rats.

Relatively few molecular markers of stress have been studied in aged individuals. Interactions of age and stress on adrenal neuropeptide Y (NPY) and preproenkephalin (ppENK) expression have not been reported. The purpose of these studies was to characterize the adrenal NPY and ppENK responses to stress using a common stressor, physical restraint for 2 h, in Fischer 344 rats at 7, 16 and 23 months of age. Northern blot techniques were used to evaluate induction by stress of adrenal NPY mRNA and adrenal ppENK mRNA. Two humoral responses to stress, serum glucose and corticosterone, were measured to corroborate that a stress response occurred. We observed that the induction by stress of adrenal NPY mRNA is impaired with age but the stress-induced elevation of adrenal ppENK mRNA, blood glucose, and corticosterone show no evidence of age-related impairments.

Connective tissue and joint disease in diabetes mellitus.

Connective tissue is ubiquitous and subject to alterations that result in changes in the extracellular matrix of vessels and tissues leading to the long-term complications of diabetes. This article reviews only those abnormalities of interstitial connective tissue involving skeleton, joints, skin, and periarticular tissues. Abnormalities in the skin and periarticular tissues result in syndromes limiting joint movement, including limited joint mobility, Dupuytren disease, flexor tenosynovitis, carpal tunnel syndrome, stiff-hand syndrome, and shoulder-hand reflex dystrophy. Of these, only limited joint mobility and stiff-hand syndrome occur exclusively in patients with diabetes. In all of these conditions, advanced glycation end products are thought to form as a result of nonenzymatic reaction of glucose with proteins, causing stiffening.

Cognitive and behavioral knowledge about insulin-dependent diabetes among children and parents.

Youngster's knowledge about insulin-dependent diabetes was assessed across three domains: (1) general information; (2) problem solving and (3) skill at urine testing and self-injection. These youngster's parents completed the general information and problem-solving components of the assessment battery. All test instruments were showed good reliability. The test of problem solving was more difficult than the test of general information for both parents and patients. Mothers were more knowledgeable than fathers and children. Girls performed more accurately than boys, and older children obtained better scores than did younger children. Nevertheless, more than 80% of the youngsters made significant errors on urine testing and almost 40% made serious errors in self-injection. A number of other knowledge deficits were also noted. Duration of diabetes was not related to any of the knowledge measures. Intercorrelations between scores on the assessment instruments indicated that skill at urine testing or self-injection was not highly related to other types of knowledge about diabetes. Furthermore, knowledge in one content are was not usually predictive of knowledge in another content area. The results of this study emphasize the importance of measuring knowledge from several different domains. Patient variables such as sex and age need to be given further consideration in the development and use of patient educational programs. Regular assessment of patients' and parents' knowledge of all critical aspects of diabetes home management seems essential.

Low dose single weekly injections of growth hormone: response during first year of therapy of hypopituitarism.

Initial year growth responses to single weekly injections of 2.5 units human growth hormone (hGH) in 29 patients with hypopituitarism (130 units/yr/patient) were compared to responses in a series using smaller doses in conjunction with androgen (48 to 112 units/yr); the US collaborative study experience with the standard dose (2 units 3 times/wk = 312 units/yr), and with two size-adjusted doses (0.06 units/kg 3 times/wk = 212 +/- 94 SD units/yr, 0.03 units/kg 3 times/wk = 116 +/- 33 units/yr); and to the British experience with much larger doses (1,040 units/yr). During the first year of hGH treatment our patients grew an average 13% faster than the androgen-supplemented and collaborative study-0.03 units/kg/dose groups. They had a similar pace to the collaborative study-312 units/yr and 0.06 units/kg/dose patients, but grew 15% more slowly than did the British patients. Growth response correlated positively with age and negatively with hGH dose per kilogram of body weight. Of 17 patients with isolated growth hormone deficiency ten developed hypothyroidism with hGH therapy, leading to a policy of routine adjunctive thyroxine replacement.

Postoperative intravenous infusion of alprostadil (PGE1) does not improve renal function in hepatic transplant recipients.

BACKGROUND: Acute renal failure is a frequent complication following orthotopic hepatic transplantation. A reduction in the synthesis of intrarenal vasodilator prostaglandins has been proposed as having an important role in the pathogenesis of renal insufficiency associated with hepatic dysfunction, as well as in the nephrotoxicity associated with cyclosporine and FK506 immunosuppressive therapy. Therefore, administration of vasodilator prostaglandins may improve renal function following hepatic transplantation. This study was designed to determine the effect of continuous intravenous alprostadil (prostaglandin E1) on postoperative renal function in hepatic transplant patients. STUDY DESIGN: In a randomized, double-blind, placebo-controlled trial, 21 patients who had undergone orthotopic hepatic transplantation and had a measured postoperative glomerular filtration rate (GFR) of less that 50 mL/minute received intravenous alprostadil at 0.6 microgram/kg/hour or placebo for five days. Glomerular filtration rate and effective renal plasma flow (ERPF) were measured by a single-injection clearance method using a radionuclide agent in 53 patients within 12 hours after admission to our surgical intensive care unit. Usual postoperative care was not modified. Radionuclide GFR and ERPF measurements were repeated on postoperative day 3. Serum creatinine was measured preoperatively and postoperatively on day 3 and on day 5. A 24-hour serum creatinine clearance was measured on days 1, 5, and 14. Urine output was recorded hourly during the infusion period. RESULTS: Ten patients received alprostadil, and 11 patients received placebo. There was a significant increase in GFR and ERPF in both groups on post-operative day 3 as compared with baseline values. There was no difference in GFR and ERPF between the two groups on day 3 (48 +/- 18 and 246 +/- 68 mL/minute in the alprostadil group compared with 53 +/- 17 and 270 +/- 131 mL/minute in the placebo group). Serum creatinine levels increased on day 3 in both groups but returned to baseline by day 5. CONCLUSIONS: These results indicate that a reversible decrease in GFR is common on hepatic transplant patients during the postoperative period. Administration of a continuous intravenous infusion of alprostadil in the immediate postoperative period had no effect on renal function when compared with placebo.

Anesthesia: what the internist needs to know.

We have attempted to acquaint the internist with some aspects of anesthesiology that need to be kept in mind when performing perioperative consultation. Communication among and between the entire operative team will reduce risk and untoward reactions and will enhance the likelihood of successful outcome and rapid recovery.

Treatment of type 2 diabetes mellitus in children and adolescents.

The treatment of type 2 diabetes mellitus (DM) is directed at decreasing insulin resistance and increasing insulin secretion. alpha-Glucosidase inhibitors slow carbohydrate absorption, resulting in reduced postprandial hyperglycemia; thiazolidinediones increase insulin sensitivity, especially in muscle and adipocytes; metformin decreases hepatic gluconeogenesis; sulfonylureas result in prolonged increases in insulin secretion; and meglitinide causes rapid, short-lived increases in insulin secretion. A survey of 130 pediatric endocrinology practices in the USA and Canada indicated that 48% of children with type 2 DM were treated with insulin and 44% with one or more oral hypoglycemic agents (OHA). Of those treated with OHA, 71% received metformin, 46% sulfonylureas, 9% thiazolidinediones and 4% meglitinide. Similarly, in the three university-based diabetes centers in Florida, 50% of the children with type 2 DM were treated with OHA. Treatment is based on symptoms at presentation. Patients identified on routine testing are often treated with exercise and diet alone. Those who are mildly symptomatic at onset are often started on OHA. Patients with substantial ketosis, ketoacidosis or markedly elevated blood glucose levels are initially treated with insulin, followed by a tapering of the dose and the addition of an OHA after blood glucose control is established and symptoms subside. There are no studies of the efficacy or compliance with treatment for type 2 DM in adolescents. Treatment is currently based on the clinical experience with adults. Controlled clinical trials in children are essential.

Residential treatment for youngsters with difficult-to-manage insulin dependent diabetes mellitus.

A descriptive outcome study of 52 children with insulin-dependent diabetes mellitus (IDDM) admitted to a residential treatment program over 6 years. Criteria for admission included repeated hospitalizations for diabetes-related problems, excessive school absences, and/or familial disruption. Residential treatment included individual, group, and family psychotherapy, diabetes education, and close medical supervision. The design included collection of data before, during and after treatment. Children admitted to the residential unit were compared to a population of pediatric IDDM outpatients from the same geographical area. Treatment was associated with a reduction in diabetes-related hospitalizations, improved school attendance, decreased glycosylated hemoglobin levels, weight gain, individualized insulin changes, improved knowledge about diabetes, and a normalization of attitudes towards this disease.

New developments in type 1 (insulin-dependent) diabetes.

The Diabetes Control and Complications Trial has conclusively demonstrated that improved metabolic control leads to reduction in the rate of microvascular complications of diabetes. In order to allow patients to achieve improved metabolic control, much research has focused on improved methods of glucose monitoring and more physiologic ways of insulin delivery. The 2 most promising methods of minimally invasive blood glucose monitoring are the Glucowatch, using the technique of reverse iontophoresis to measure interstitial fluid glucose levels every twenty minutes and an implantable sensor, in which a catheter resembling that used for insulin delivery through a pump is impregnated with glucose oxidase at the tip. This device monitors blood sugars every few minutes, but like a holter monitor, must be downloaded in the physician's office. Still under development are (1) implantable subcutaneous sensors with a high and low blood glucose alarm and (2) sensors in which the patient will be able to download the data using a home PC. Advances in insulin delivery have included the availability of new insulin analogs which more closely simulate endogenous insulin release, with rapid acting analogs simulating the increase in insulin production that normally occurs after meals. Phase III clinical trials are in progress of a long-acting basal insulin without peak actions to simulate the low dose continuous production of the insulin which normally inhibits hepatic glucose production. In addition, use of the insulin pump has increased markedly since publication of the DCCT with the greatest increase being among adolescents. In addition to advances in treatment of diabetes, research has continued on curing the disease using islet cell transplantation and preventing the disease with agents such as insulin (DPT-1 Trial) and nicotinamide (ENDIT). This article provides an overview of recent advances in diabetes management and prevention.

Accuracy of injection site identification among children with insulin dependent diabetes mellitus: a comparison of traditional and new visual aids.

Children with insulin-dependent diabetes mellitus (IDDM) typically self-inject insulin twice daily. Injection sites must be rotated with each insulin administration to avoid lipohypertrophy. Lipohypertrophy results in erratic insulin release and threatens metabolic stability. To aid rotation, children are usually provided with a picture of a human figure with injection sites identified within a grid. Children often have difficulty using the charts or lack the skills necessary to identify injection sites. An alternative three-dimensional visual aid, a pair of "injection bears", simplifies injection site identification. Fifty-eight 6- to 11-year-old children with IDDM identified 10 injection sites using both the injection chart and the injection bears. Accuracy of injection site identification was compared on five subcomponents. Forty-four percent of informants recalled that their doctors recommended using injection charts. Of those recalling the recommendation, 81% never or rarely used charts at home. Thirty-nine percent of the informants reported a history of lipohypertrophy. Matched sample t-tests demonstrated that children committed significantly fewer identification errors on all subcomponents (P < or = .05) when using the injection bears. Chi square analyses indicated a significant preference (P < or = .05) for the injection bears, which may be a useful tool for insulin injection rotation with younger children.

Diagnosis and treatment of an adolescent with comorbid type 1 diabetes mellitus and anorexia nervosa.

The authors describe the successful treatment of a 17-year-old female with comorbid type 1 diabetes mellitus and anorexia nervosa within the context of a residential program in a tertiary care facility. Assessment and treatment of the complex combinations of the psychological and medical symptoms involved in this patient required the interaction of medical, psychological, and nutritional services. Diagnostic and treatment challenges are discussed.