Oral ghrelin receptor agonist MK-0677 increases serum insulin-like growth factor 1 in hemodialysis patients: a randomized blinded study.

Background: Protein-energy wasting (PEW) in end-stage renal disease (ESRD) patients is associated with increased morbidity and mortality, but options for treatment are limited. Growth hormone (GH) increases insulin-like growth factor 1 (IGF-1), with improved nutritional parameters, but must be given subcutaneously and does not provide normal GH secretion patterns. MK-0677, an oral ghrelin receptor agonist (GRA), maintains normal GH secretion and increases lean body mass in normal subjects; it has not been studied in dialysis patients, an essential step in assessing efficacy and safety prior to clinical trials. Methods: We performed a randomized crossover double-blind study in assessing the effect of MK-0677 versus placebo on IGF-1 levels, the primary outcome, in hemodialysis patients. In total, 26 subjects enrolled and 22 completed the 3-month crossover study. Results: The geometric mean IGF-1 was 1.07-fold greater [95% confidence interval (CI) 0.89-1.27; P = 0.718] after placebo. In patients receiving MK-0677, the geometric mean IGF-1 were 1.76-fold greater (95% CI 1.48-2.10; P < 0.001) following MK-0677. When the data were adjusted for preintervention IGF-1 concentration, the ratio of geometric means (MK-0677 relative to placebo) for the pre- versus postintervention change in the IGF-1 was 1.65 (95% CI 1.33-2.04; P < 0.001). These data demonstrate a 65% greater increase (95% CI 33-104%) in IGF-1 in MK-0677-dosed subjects compared with placebo. There were no serious adverse effects attributable to MK-0677. Conclusions: MK-0677 increased serum IGF-1 levels with minimal adverse effects in hemodialysis subjects. Studies are needed to evaluate whether long-term therapy with MK-0677 improves PEW, lean body mass, physical strength, quality of life and survival in CKD/ESRD patients.

The Ottawa SAH search algorithms: protocol for a multi- centre validation study of primary subarachnoid hemorrhage prediction models using health administrative data (the SAHepi prediction study protocol).

BACKGROUND: Conducting prospective epidemiological studies of hospitalized patients with rare diseases like primary subarachnoid hemorrhage (pSAH) are difficult due to time and budgetary constraints. Routinely collected administrative data could remove these barriers. We derived and validated 3 algorithms to identify hospitalized patients with a high probability of pSAH using administrative data. We aim to externally validate their performance in four hospitals across Canada. METHODS: Eligible patients include those ≥18 years of age admitted to these centres from January 1, 2012 to December 31, 2013. We will include patients whose discharge abstracts contain predictive variables identified in the models (ICD-10-CA diagnostic codes I60** (subarachnoid hemorrhage), I61** (intracranial hemorrhage), 162** (other nontrauma intracranial hemorrhage), I67** (other cerebrovascular disease), S06** (intracranial injury), G97 (other postprocedural nervous system disorder) and CCI procedural codes 1JW51 (occlusion of intracranial vessels), 1JE51 (carotid artery inclusion), 3JW10 (intracranial vessel imaging), 3FY20 (CT scan (soft tissue of neck)), and 3OT20 (CT scan (abdominal cavity)). The algorithms will be applied to each patient and the diagnosis confirmed via chart review. We will assess each model's sensitivity, specificity, negative and positive predictive value across the sites. DISCUSSION: Validating the Ottawa SAH Prediction Algorithms will provide a way to accurately identify large SAH cohorts, thereby furthering research and altering care.

Markedly increased incidence of critical illness in adults with Type 1 diabetes.

AIMS: To compare the incidence of and mortality after intensive care unit admission in adults with paediatric-onset Type 1 diabetes vs the general population. METHODS: Using population-based administrative data from Manitoba, Canada, we identified 814 cases of paediatric-onset Type 1 diabetes, and 3579 general population controls matched on age, sex and region of residence. We estimated the incidence of intensive care unit admission in adulthood, and compared the findings between populations using incidence rate ratios and multivariable Cox proportional hazards regression, adjusting for age, sex, comorbidity and socio-economic status. We estimated age- and sex-standardized mortality rates after intensive care unit admission. RESULTS: Between January 2000 and October 2009, the average annual incidence of intensive care unit admission among prevalent cohorts was 910 per 100 000 in the Type 1 diabetes population, and 106 per 100 000 in matched controls, an eightfold increased risk (incidence rate ratio 8.6; 95% CI 5.5, 14.0). The adjusted risk of intensive care unit admission was elevated to a greater extent among women with Type 1 diabetes compared with matched women (hazard ratio 14.7; 95% CI 7.2, 29.4) than among men with Type 1 diabetes compared with matched men (hazard ratio 4.92; 95% CI 10.3, 2.36) The most common reasons for admission in the diabetes cohort were diabetic ketoacidosis, infection and ischaemic heart disease. At 30%, 5-year mortality was higher in the diabetes cohort than in the matched cohort (relative risk 5.7; 95% CI 1.2, 8.9). CONCLUSIONS: Compared with the general population, the risk of intensive care unit admission was higher in adults with paediatric-onset Type 1 diabetes, and mortality after admission was also higher.

Validation of a short questionnaire for estimating dietary calcium intakes.

UNLABELLED: Concern about calcium supplements, and mainly minor side effects (e.g. constipation) impacting on compliance, means that assessing dietary calcium intake is important. There is no suitable biomarker. Compared to food diaries, a short questionnaire was an efficient way of confirming that patients had adequate calcium intakes (>700 or >1,000 mg) INTRODUCTION: Calcium is usually given alongside treatments for osteoporosis, but recent concerns about potential side effects have led to questioning whether supplements are always necessary. It is difficult to assess calcium intake in a clinical setting and be certain that the patient is getting enough calcium. The aim of this study was to determine whether a short questionnaire for estimating dietary calcium intakes in a clinical setting was fit for purpose. METHODS: We assessed dietary calcium intakes using a short questionnaire (CaQ) in patients attending an osteoporosis clinic (n = 117) and compared them with calcium intakes obtained from a 7-day food diary (n = 72) and a food frequency questionnaire (FFQ) (n = 33). RESULTS: Mean (SD) daily calcium intakes from the CaQ were 836 (348) mg; from the diaries, 949 (384) mg; and from the FFQ, 1,141 (387) mg. The positive predictive value (PPV) was >80% for calcium cut-offs > 700 mg and 70% for cut-offs > 1,000 mg. The calcium intakes for the false positives results were not far below the cut-off. For 1,200 mg, the PPV was 67% or less. CONCLUSION: The CaQ is an adequate tool for assessing whether a patient has daily calcium intakes above 700 or 1,000 mg; if below these cut-offs, it is possible that the patient still has enough calcium in the diet, which could be clarified by questioning the patient further. As there were few patients with calcium intakes above 1,200 mg a day, the CaQ cannot be recommended as a tool for confirming higher dietary calcium intakes.

The Effect of Frailty on Independent Living After Surgery: A Population-Based Retrospective Cohort Study.

BACKGROUND: Most people value quality of life over mere duration. At least 50% of people are extremely averse to ever living in a nursing home (NH). OBJECTIVES: Assess whether pre-operative frailty is associated with new, post-operative NH placement. DESIGN, SETTING: Retrospective, population-based cohort study in the Canadian province of Manitoba, 2000-2017. PARTICIPANTS: 7408 persons ≥65 years undergoing any of 16 specific, elective, noncardiac surgeries of varying Operative Surgical Stress (OSS). MEASUREMENTS: The primary outcome was new admission to a NH, or being placed on a waiting list for a NH, within 180 days of index hospital admission, among index hospital survivors. Frailty was assessed from administrative data by the Preoperative Frailty Index (pFI), which ranges 0-1. Other outcomes were 30-day and 90-180 day mortality, and post-hospital medical resource use to 180 days. Analyses used multivariable regression models, adjusted for age, sex, OSS, year of surgery, anesthetic technique, and socioeconomic status. P-values were adjusted for the six outcomes. RESULTS: Subjects had mean age (±SD) of 74±7 yrs; 61% were male. pFI ranged 0-0.68, with a mean±SD of 0.21±0.09. All six outcomes were significantly associated with greater frailty. Each additional 0.1 unit increase in pFI was associated with a hazard ratio for new NH admission or wait-listing of 3.01 (p<0.0006). CONCLUSIONS: While our study agrees with prior work indicating that greater frailty is associated with higher probability of post-operative discharge to a NH, it overcomes a number of limitations of all prior work. Strong arguments follow that prospective surgical candidates be evaluated for their degree of frailty, and that their informed consent include discussion of the possibility of survival with loss of independence.

Cattle, sheep and pigs vaccinated against foot and mouth disease: does trade in these animals and their products present a risk of transmitting the disease?

The foot and mouth disease (FMD) status of a country or region has a profound bearing on access to export markets for live animals and animal products. In countries without FMD-free status, and in accordance with the international standards of the World Organisation for Animal Health (OIE), restrictions may be applied to trade in both vaccinated and unvaccinated animals and their products. Available information suggests that, provided there is compliance with essential criteria concerning vaccines, vaccination and other zoosanitary measures (especially quarantine and ante- and post-mortem inspection), the risk of spreading FMD through the importation of vaccinated cattle, sheep and pigs is extremely small. The risk from products derived from vaccinated animals is even smaller, provided that appropriate risk mitigation measures are applied. Knowledge of the zoosanitary status of the exporting country is critical for risk assessment, but can be difficult to verify. Although empirical evidence and practical experience strongly indicate low risk, it is not possible to assert that the risk is zero for vaccinated animals or their products. In the absence of key factual data, risk analysis is only practicable on a qualitative or semi-quantitative basis. However, a very low level of risk is both unavoidable and acceptable if such trade is to be conducted.

Tachykinin receptor antagonists inhibit hyperpnea-induced bronchoconstriction in guinea pigs.

We tested the hypothesis that hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH) are mediated through stimulation of NK-1 and NK-2 receptors in guinea pigs. We first established the efficacy and selectivity of (+/-) CP-96,345 (3 mg/kg i.v.) and of SR-48,968 (300 micrograms/kg i.v.) as NK-1 and NK-2 antagonists, respectively. (+/-) CP-96,345 substantially attenuated bronchoconstriction and systemic vascular leak caused by administration of Sar9,Met(O2)11-Substance P (a specific NK-1 agonist), but had no effect upon bronchoconstriction induced by selective NK-2 stimulation with Nle10-Neurokinin A[4-10]. Conversely, SR-48,968 antagonized the bronchoconstrictor response to Nle10-NKA[4-10], right-shifting the dose-response curve by 2 log units, but had no effect on Sar9, Met(O2)11-SP-induced bronchoconstriction. Anesthetized, tracheostomized, opened-chest male Hartley guinea pigs were pretreated with (+/-) CP-96,345 (3 mg/kg i.v.), SR-48,968 (300 micrograms/kg i.v.), or their respective vehicles, and Evans blue dye (30 mg/kg i.v.) to label circulating albumin. 10 min isocapnic dry gas hyperpnea (12 ml/kg, 150 breaths/min) provoked HIB and HIBVH in vehicle-treated animals. (+/-) CP-96,345 reduced the magnitude of HIB by one-half (peak posthyperpnea RL 7.8 +/- 1.9 [SE] times prehyperpnea baseline versus 16.1 +/- 2.6, vehicle-treated; P < or = 0.0001, ANOVA); SR-48,968 blocked HIB more completely (peak posthyperpnea RL 5.1 +/- 1.7 [SE] times prehyperpnea baseline versus 19.3 +/- 2.8, vehicle-treated; P < 0.0001, ANOVA). Neither drug reduced HIBVH. We conclude that dry gas hyperpnea causes bronchoconstriction in guinea pigs through activation of tachykinin receptors. The differential effects of neurokinin receptor blockade on HIB and HIBVH demonstrate that hyperpnea-induced airflow obstruction is not primarily a consequence of hyperpnea-induced bronchovascular leak.

Hypertonicity, but not hypothermia, elicits substance P release from rat C-fiber neurons in primary culture.

Isocapnic dry gas hyperventilation provokes hyperpnea-induced bronchoconstriction in guinea pigs by releasing tachykinins from airway sensory C-fiber neurons. It is unknown whether dry gas hyperpnea directly stimulates C-fibers to release tachykinins, or whether this physical stimulus initiates a mediator cascade that indirectly stimulates C-fiber tachykinin release. We tested the hypotheses that mucosal hypothermia and/or hyperosmolarity--physical consequences of airway heat and water loss imposed by dry gas hyperpnea--can directly stimulate C-fiber tachykinin release. Neurons isolated from neonatal rat dorsal root ganglia were maintained in primary culture for 1 wk. Cells were then exposed for 30 min at 37 degrees C to graded concentrations of NaCl, mannitol, sucrose, or glycerol (0-600 mOsm) added to isotonic medium, or to isotonic medium at 25 degrees C without or with 462 mOsm mannitol added. Fractional release of substance P (SP) was calculated from supernatant and intracellular SP contents following exposure. Hyperosmolar solutions containing excess NaCl, mannitol, or sucrose all increased fractional SP release equivalently, in an osmolarity-dependent fashion. In marked contrast, hypothermia had no effect on fractional SP release under isotonic or hypertonic conditions. Thus, hyperosmolarity, but not hypothermia, can directly stimulate tachykinin release from cultured rat sensory C-fibers. The lack of effect of glycerol, a solute which quickly crosses cell membranes, suggests that neuronal volume change represents the physical stimulus transduced by C-fibers during hyperosmolar exposure.

Delineation of the endocytic pathway of substance P and its seven-transmembrane domain NK1 receptor.

Many of the actions of the neuropeptide substance P (SP) that are mediated by the neurokinin 1 receptor (NK1-R) desensitize and resensitize, which may be associated with NK1-R endocytosis and recycling. We delineated this endocytic pathway in transfected cells by confocal microscopy using cyanine 3-SP and NK1-R antibodies. SP and the NK1-R were internalized into the same clathrin immunoreactive vesicles, and then sorted into different compartments. The NK1-R was colocalized with a marker of early endosomes, but not with markers of late endosomes or lysosomes. We quantified the NK1-R at the cell surface by incubating cells with an antibody to an extracellular epitope. After exposure to SP, there was a loss and subsequent recovery of surface NK1-R. The loss was prevented by hypertonic sucrose and potassium depletion, inhibitors of clathrin-mediated endocytosis. Recovery was independent of new protein synthesis because it was unaffected by cycloheximide. Recovery required endosomal acidification because it was prevented by an H(+)-ATPase inhibitor. The fate of internalized 125I-SP was examined by chromatography. SP was intact at the cell surface and in early endosomes, but slowly degraded in perinuclear vesicles. We conclude that SP induces clathrin-dependent internalization of the NK1-R. The SP/NK1-R complex dissociates in acidified endosomes. SP is degraded, whereas the NK1-R recycles to the cell surface.

Risk of early mortality after cemented compared with cementless total hip arthroplasty: a nationwide matched cohort study.

AIMS: It has been suggested that cemented fixation of total hip arthroplasty (THA) is associated with an increased peri-operative mortality compared with cementless THA. Our aim was to investigate this through a nationwide matched cohort study adjusting for age, comorbidity, and socioeconomic background. PATIENTS AND METHODS: A total of 178 784 patients with osteoarthritis who underwent either cemented or cementless THA from the Swedish Hip Arthroplasty Register were matched with 862 294 controls from the general population. Information about the causes of death, comorbidities, and socioeconomic background was obtained. Mortality within the first 90 days after the operation was the primary outcome measure. RESULTS: Patients who underwent cemented THA had an increased risk of death during the first 14 days compared with the controls (hazard ratio (HR) 1.3, confidence interval (CI) 1.11 to 1.44), corresponding to an absolute increase in risk of five deaths per 10 000 observations. No such early increase of risk was seen in those who underwent cementless THA. Between days 15 and 29 the risk of mortality was decreased for those with cemented THA (HR 0.7, CI 0.62 to 0.87). Between days 30 and 90 all patients undergoing THA, irrespective of the mode of fixation, had a lower risk of death than controls. Patients selected for cementless fixation were younger, healthier and had a higher level of education and income than those selected for cemented THA. A supplementary analysis of 16 556 hybrid THAs indicated that cementation of the femoral component was associated with a slight increase in mortality up to 15 days, whereas no such increase in mortality was seen in those with a cemented acetabular component combined with a cementless femoral component. CONCLUSION: This nationwide matched cohort study indicates that patients receiving cemented THA have a minimally increased relative risk of early mortality that is reversed from day 15 and thereafter. The absolute increase in risk is very small. Our findings lend support to the idea that cementation of the femoral component is more dangerous than cementation of the acetabular component. Cite this article: Bone Joint J 2017;99-B:37-43.

Prevention of relapse in residual depression by cognitive therapy: a controlled trial.

BACKGROUND: Previous studies indicate that depressed patients with partial remission and residual symptoms following antidepressant treatment are common and have high rates of relapse. There is evidence that cognitive therapy may reduce relapse rates in depression. METHODS: One hundred fifty-eight patients with recent major depression, partially remitted with antidepressant treatment (mean daily doses equivalent to 185 mg of amitriptyline or 33 mg of fluoxetine) but with residual symptoms of 2 to 18 months' duration, were included in a controlled trial. Subjects were randomized to receive clinical management alone or clinical management plus cognitive therapy for 16 sessions during 20 weeks, with 2 subsequent booster sessions. Subjects were assessed regularly throughout the 20 weeks' treatment and for a further year. They received continuation and maintenance antidepressants at the same dose throughout. RESULTS: Cognitive therapy reduced relapse rates for acute major depression and persistent severe residual symptoms, in both intention to treat and treated per protocol samples. The cumulative relapse rate at 68 weeks was reduced significantly, from 47% in the clinical management control group to 29% with cognitive therapy (hazard ratio 0.54; 95% confidence interval, 0.32-0.93; intention to treat analysis). Cognitive therapy also increased full remission rates at 20 weeks but did not significantly improve symptom ratings. CONCLUSION: In this difficult-to-treat group of patients with residual depression who showed only partial response despite antidepressant treatment, cognitive therapy produced worthwhile benefit.

Role of eicosanoids in hyperpnea-induced airway responses in guinea pigs.

Guinea pigs mechanically hyperventilated with dry gas exhibit hyperpnea-induced bronchoconstriction (HIB) and hyperpnea-induced bronchovascular hyperpermeability (HIBVH). Tachykinins released from airway C-fiber neurons are the central mediators of guinea pig HIB but play only a contributory role in HIBVH. Recent studies suggest that eicosanoid mediators can provoke bronchoconstriction and bronchovascular hyperpermeability, are released by dry gas hyperpnea, and can themselves elicit or modulate tachykinin release. We therefore hypothesized that eicosanoids may participate in HIB and/or HIBVH. To test these hypotheses, we analyzed respiratory system resistance changes and Evans blue-labeled albumin extravasation into the airways of 60 tracheostomized and mechanically ventilated guinea pigs. Animals were subjected to 10 min of isocapnic dry gas hyperpnea or to quiet breathing of humidified gas and received as pretreatment either piroxicam, a cyclooxygenase (CO) inhibitor; A-63162, a 5-lipoxygenase (5-LO) inhibitor; BW-755c, a combined CO and 5-LO inhibitor; ICI-198,615, a leukotriene D4 receptor antagonist; or no drug. HIB was substantially (50-80%) reduced by each of the four eicosanoid-modulating drugs. In contrast, HIBVH was reduced only by BW-755c, and this effect occurred only within the extrapulmonary airways (42% reduction). These data indicate that both CO and 5-LO products, including leukotriene D4, participate in the pathogenesis of HIB but that, like tachykinins, they play only a small contributory role in HIBVH. Together with our previous demonstration that sensory neuropeptide release is critical for the occurrence of HIB, we conclude that the roles of eicosanoids and tachykinins in guinea pig HIB are interdependent.

Time course of bronchoconstriction induced by dry gas hyperpnea in guinea pigs.

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of tachykinins in hyperpnea-induced bronchovascular hyperpermeability in guinea pigs.

Isocapnic dry gas hyperpnea causes bronchoconstriction in guinea pigs that is mediated by release of tachykinins from airway sensory nerves. Exogenous neuropeptides can induce microvascular leak. Therefore we tested whether dry gas hyperpnea also elicits bronchovascular hyperpermeability by measuring Evans blue-labeled albumin extravasation along the airways of mechanically ventilated guinea pigs. We found that 1) room temperature dry gas hyperpnea increased Evans blue extravasation in extrapulmonary and intrapulmonary airways as a specific consequence of local airway heat/water losses, 2) capsaicin pretreatment ablated the bronchoconstrictor response to dry gas hyperpnea and reduced bronchovascular leak only in intrapulmonary airways, 3) phosphoramidon given to capsaicin-pretreated animals partially restored dry gas hyperpnea-induced bronchoconstriction and increased the vascular hyperpermeability response to hyperpnea in intrapulmonary airways, and 4) propranolol administration had no important effects on any of these airway responses. We conclude that dry gas hyperpnea causes bronchovascular hyperpermeability in guinea pigs. Tachykinins have a dominant role in this response in the intrapulmonary airways, although another mechanism may also contribute to the microvascular leak in the extrapulmonary airways.

Laparoscopic ultrasound vs triphasic computed tomography for detecting liver tumors.

BACKGROUND: Accurate staging of malignant tumors in the liver has major implications in defining prognosis and guiding both surgical and nonsurgical therapy. Intraoperative ultrasound in open surgery compares favorably with computed tomography (CT) in the detection of liver tumors; however, there is little experience with laparoscopic ultrasound (LUS). HYPOTHESIS: Laparoscopic ultrasound is more sensitive than triphasic CT for detecting primary and metastatic liver tumors. DESIGN: Prospective study. SETTING: University hospital. PATIENTS: Fifty-five patients with a total of 222 lesions, including primary and metastatic liver tumors, who underwent both CT examinations and LUS as a part of a tumor ablation procedure. INTERVENTIONS: Triphasic spiral CT scans of the liver were obtained within 1 week before surgery. Liver LUS was performed with a linear 7.5-MHz side-viewing laparoscopic transducer. RESULTS: The LUS detected all 201 tumors seen on preoperative CT and detected 21 additional tumors (9.5%) in 11 patients (20.0%). These tumors missed by CT ranged in size from 0.3 to 2.7 cm. Smaller tumors tended to be missed by CT scan (28.6% of the lesions <1 cm, 15.8% of those 1-2 cm, 4% of those 2-3 cm, and 0% of those >3 cm), as did those in segments III and IV. There was good correlation between the size of lesions imaged by the 2 modalities (Pearson r = 0.86; P<.001). CONCLUSION: Laparoscopic ultrasound offers increased sensitivity over CT for the detection of liver tumors, especially for smaller lesions. This study documents the ability of LUS in detecting liver tumors and argues for more widespread use in laparoscopic staging procedures.

Selective use of tube cholecystostomy with interval laparoscopic cholecystectomy in acute cholecystitis.

HYPOTHESIS: Tube cholecystostomy followed by interval laparoscopic cholecystectomy is a sale and efficacious treatment option in critically ill patients with acute cholecystitis. DESIGN: Retrospective cohort study within a 4 1/2%-year period. SETTING: University hospital. PATIENTS: Of 324 patients who underwent laparoscopic cholecystectomy, 65 (20%) had acute cholecystitis; 15 of these 65 patients (mean age, 75 years) underwent tube cholecystostomy. INTERVENTION: Thirteen patients at high risk for general anesthesia because of underlying medical conditions underwent percutaneous tube cholecystostomy with local anesthesia. Laparoscopic tube cholecystostomy was performed on 2 patients during attempted laparoscopic cholecystectomy because of severe inflammation. Interval laparoscopic cholecystectomy was attempted after an average of 12 weeks. MAIN OUTCOME MEASURES: Technical details and clinical outcome. RESULTS: Prompt clinical response was observed in 13 (87%) of the patients after tube cholecystostomy. Twelve patients (80%) underwent interval cholecystectomy. Laparoscopic cholecystectomy was attempted in 11 patients and was successful in 10 (91%), with 1 conversion to open cholecystectomy. One patient had interval open cholecystectomy during definitive operation for esophageal cancer and another had emergency open cholecystectomy due to tube dislodgment. Two patients (13%) had complications related to tube cholecystostomy and 2 patients died from sepsis before interval operation. One patient died from sepsis after combined esophagectomy and cholecystectomy. Postoperative minor complications developed in 2 patients. At a mean follow-up of 16.7 months (range, 0.5-53 months), all patients were free of biliary symptoms. CONCLUSIONS: Tube cholecystostomy allowed for resolution of sepsis and delay of definitive surgery in selected patients. Interval laparoscopic cholecystectomy was safely performed once sepsis and acute infection had resolved in this patient group at high risk for general anesthesia and conversion to open cholecystectomy. Just as catheter drainage of acute infection with interval appendectomy is accepted in patients with periappendiceal abscess, tube cholecystostomy with interval laparoscopic cholecystectomy should have a role in the management of selected patients with acute cholecystitis.

A national survey of school-based, adolescent suicide prevention programs.

A national survey of suicide prevention programs was conducted to determine the number, distribution and content of school-based, curriculum programs for adolescents. One hundred fifteen programs were identified. The total number of students and schools targeted for prevention efforts more than doubled during the academic years 1984/1985 to 1986/1987. Content of the programs was similar, with nearly all including information on suicide warning signs and other facts, as well as on accessing community mental health resources. Most included a separate component for school staff and parents. Ninety-five percent subscribed to the view that suicide is most commonly a response to extreme stress or pressure and could happen to anyone. Possible negative implications of this "stress model" of suicide were discussed. While this survey plays an important first step in providing a description of these programs, more evaluative research is needed to determine what effect, if any, these programs have on suicidal behavior.

The impact of curriculum-based suicide prevention programs for teenagers.

The impact of three school-based suicide prevention programs was assessed by comparing attitudes and knowledge of 758 9th and 10th graders with those of 680 control pupils, matched on age, ethnicity, and socioeconomic status at the school level, who did not receive the programs. Evaluations were conducted before exposure to the programs and again 1 month later. A large majority of students knew and subscribed to some of the more important program goals before exposure to the program. There was little evidence of program impact among the minority that did not. Most students were interested by the programs, and positive reactions were more common among female and minority students.