Are cost advantages from a modern Indian hospital transferable to the United States?

BACKGROUND: Multiple modern Indian hospitals operate at very low cost while meeting US-equivalent quality accreditation standards. Though US hospitals face intensifying pressure to lower their cost, including proposals to extend Medicare payment rates to all admissions, the transferability of Indian hospitals' cost advantages to US peers remains unclear. METHODS: Using time-driven activity-based costing methods, we estimate the average cost of personnel and space for an elective coronary artery bypass graft (CABG) surgery at two American hospitals and one Indian hospital (NH). All three hospitals are Joint Commission accredited and have reputations for use of modern performance management methods. Our case study applies several analytic steps to distinguish transferable from non-transferable sources of NH's cost savings. RESULTS: After removing non-transferable sources of efficiency, NH's residual cost advantage primarily rests on shifting tasks to less-credentialed and/or less-experienced personnel who are supervised by highly-skilled personnel when perceived risk of complications is low. NH's high annual CABG volume facilitates such supervised work "downshifting." The study is subject to limitations inherent in case studies, does not account for the younger age of NH's patients, or capture savings attributable to NH's negligible frequency of re-admission or post-acute care facility placement. CONCLUSIONS: Most transferable bases for a modern Indian hospital's cost advantage would require more flexible American states' hospital and health professional licensing regulations, greater family participation in inpatient care, and stronger support by hospital executives and clinicians for substantially lowering the cost of care via regionalization of complex surgeries and weekend use of costly operating rooms.

Enhancing human aspects of care with young people with muscular dystrophy: Results from a participatory qualitative study with clinicians.

BACKGROUND: Most research into clinical care of Duchenne or Becker dystrophinopathies (MD) has focused on slowing progressive muscular weakness and extending lifespan. Scarce attention has been paid to the "human" aspects of care such as psychosocial health, living a fulfilling life, or dealing with disability stigma. This study partnered with clinicians to identify and address local and systemic barriers to these human aspects of care. METHODS: We employed a participatory qualitative design at a multidisciplinary MD clinic using 2 methods: (a) ethnographic observations over a 6-month period of clinic visits of children with MD and families, involving 12 clinicians, and (b) 3 "dialogues" (2-way discussions) with these clinicians to collaboratively analyze practices and co-produce recommendations for change. RESULTS: Our methods produced rich data that, when coanalyzed with clinicians and in consultation with a family advisor, provided deep insights into the practices and underlying assumptions of a neuromuscular clinic. Staff recognized the importance of the human aspects of care but, in reviewing the observational data, identified that it was given insufficient attention in (a) routine clinical processes, (b) clinician-family patterns of interaction, and (c) staffing allocations. CONCLUSION: Although the human aspects of care were important to clinicians in the MD clinic, the routines and nature of the clinic meant these were frequently sidelined for biomedical objectives. We present collaboratively produced practical recommendations toward addressing this disjunction between ideals and practice including developing flexibility to tailor appointment frequency, composition, and length; providing time and physical space for psychosocial aspects of care; and clinician skill building to support child/family expression of "negative" emotions; and discussion of sociopolitical aspects of MD such as living with disability stigma. The study offers a set of considerations that, taking into account individual differences, offer insights for similar clinics elsewhere.

Exploring Canine-Human Differences in Product Performance. Part II: Use of Modeling and Simulation to Explore the Impact of Formulation on Ciprofloxacin In Vivo Absorption and Dissolution in Dogs.

This study explored the in vivo performance of three oral ciprofloxacin formulations (oral solution, fast, or slow dissolving tablets) in beagle dogs. The in vivo absorption and dissolution behaviors, estimated with in silico mechanistic models, were compared to the results previously published in human volunteers. Six normal healthy male beagle dogs (five to completion) received three oral formulations and an intravenous infusion in a randomized crossover design. Plasma ciprofloxacin concentrations were estimated by tandem mass spectrometry detection. A mechanistic absorption model was used to predict the in vivo dissolution and absorption characteristics of the oral formulations. Canine ciprofloxacin absorption was constrained to the duodenum/jejunum. This absorption window was far narrower than that seen in humans. Furthermore, while substantial within-individual variability in drug absorption was seen in human subjects, a greater magnitude of variability was observed in dogs. For three sets of data, a lag time in gastric emptying was necessary to improve the accuracy of model-generated in vivo blood level profile predictions. In addition to species-associated dissimilarities in drug solubilization due to human versus canine differences in gastrointestinal fluid compositions, the far more rapid intestinal transit time and potential segmental differences in drug absorption needed to be considered during human-canine extrapolation of oral drug and drug product performance. Through the use of mechanistic models, the data generated in the human and canine studies contributed insights into some aspects of the interspecies differences to be considered when extrapolating oral bioavailability/formulation effect data between dogs and humans.

Time-driven activity-based costing of multivessel coronary artery bypass grafting across national boundaries to identify improvement opportunities: study protocol.

INTRODUCTION: Coronary artery bypass graft (CABG) surgery is a well-established, commonly performed treatment for coronary artery disease--a disease that affects over 10% of US adults and is a major cause of morbidity and mortality. In 2005, the mean cost for a CABG procedure among Medicare beneficiaries in the USA was $32, 201 ± $23,059. The same operation reportedly costs less than $2000 to produce in India. The goals of the proposed study are to (1) identify the difference in the costs incurred to perform CABG surgery by three Joint Commission accredited hospitals with reputations for high quality and efficiency and (2) characterise the opportunity to reduce the cost of performing CABG surgery. METHODS AND ANALYSIS: We use time-driven activity-based costing (TDABC) to quantify the hospitals' costs of producing elective, multivessel CABG. TDABC estimates the costs of a given clinical service by combining information about the process of patient care delivery (specifically, the time and quantity of labour and non-labour resources utilised to perform each activity) with the unit cost of each resource used to provide the care. Resource utilisation was estimated by constructing CABG process maps for each site based on observation of care and staff interviews. Unit costs were calculated as a capacity cost rate, measured as a $/min, for each resource consumed in CABG production. Multiplying together the unit costs and resource quantities and summing across all resources used will produce the average cost of CABG production at each site. We will conclude by conducting a variance analysis of labour costs to reveal opportunities to bend the cost curve for CABG production in the USA. ETHICS AND DISSEMINATION: All our methods were exempted from review by the Stanford Institutional Review Board. Results will be published in peer-reviewed journals and presented at scientific meetings.

Condition-related predictors of successful transition from paediatric to adult care among adolescents with Type 1 diabetes.

AIMS: To describe patient attendance for adult treatment after completion by young people of a structured Diabetes Transition Clinic and to identify the predictors of non-attendance at adult clinics by young people with Type 1 diabetes transitioning from paediatric care. METHODS: Young people with Type 1 diabetes were consecutively enrolled on a Diabetes Transition Clinic programme at a Canadian paediatric teaching hospital, beginning in December 2007. Data from clinical interviews completed by an adolescent medicine specialist and an adult endocrinologist were prospectively collected at the Diabetes Transition Clinic visit in the patient's 18(th) year, before he/she was transferred at age 18 years to the adult clinic and at the first adult clinic visit. RESULTS: As of June 2011, 136 young people participating in the Diabetes Transition Clinic programme had been discharged from paediatric care at least 1 year earlier. Of these, 43 participants were lost to follow-up. Loss to follow-up was more frequent among: those who were diagnosed with diabetes before the age of 12 years; those who were taking insulin twice or three times daily rather than by pump or multiple daily injections; those who had higher HbA1c levels; those who had fewer diabetes physician visits in the year preceding the Diabetes Transition Clinic visit; and those who did not ask questions at the Diabetes Transition Clinic visit. CONCLUSIONS: Several factors easily ascertained at a clinical encounter before transition can predict the likelihood of attendance in adult care, including age at diagnosis, mode of insulin administration, frequency of physician visits, and questions asked by patients during a transition visit.

Microwave-assisted Synthesis of an Important Intermediate of Benazepril.

Rapid and efficient methods for the synthesis of an important intermediate of benazepril ethyl 3-phthalimido-2,3,4,5-tetrahydro-1H-[1]benzazepin-2-one-1-acetate under the influence of microwave irradiation are described. A comparative study of conventional and microwave assisted method is briefly discussed.

Cavoportal hemitransposition in liver transplantation.

Over the last decade a large number of patients with portal vein thrombosis have undergone successful liver transplantation. In most of these patients, simple modifications in vascular reconstruction techniques are adequate. However, anastomosis of the donor portal vein may not be possible in the presence of extensive portal and superior mesenteric venous thrombosis and in the absence of any other large tributary of the portal venous system. Cavoportal hemitransposition has been described as a salvage technique under these circumstances. We report a 43-year-old patient who underwent such a procedure and remains well 1 year later. We review the literature and discuss the implications of cavoportal hemitransposition.

Changes in serum lipoprotein profile during interferon therapy in chronic hepatitis C.

OBJECTIVES: Therapy with a interferon is associated with a rise in serum triglyceride levels, although this effect has not been well studied with newer forms of interferon or interferon in combination with ribavirin. METHODS: Review of combined data obtained from several prospective, randomized controlled clinical trials conducted in the clinical studies unit of a tertiary care referral center among patients with chronic hepatitis C undergoing treatment with various forms of a interferon, with or without the addition of ribavirin. Serum levels of triglycerides and cholesterol were measured before and during therapy. Changes in these levels were correlated with baseline characteristics. RESULTS: At baseline, the mean serum triglyceride level among 152 patients studied was 130 mg/dL (range 32-620) and was elevated above normal in three patients (2%). During therapy, triglyceride levels rose significantly early on and began to decline spontaneously after 12 wk, returning to baseline after stopping treatment. Triglyceride levels rose above 500 mg/dL in 18 patients (12%) and above 1000 mg/dL in two patients (1.3%) although none experienced acute complications or clinical symptoms. Serum cholesterol levels did not change significantly during therapy (mean at baseline 172 vs 168 mg/dL at 24 wk). Factors correlated with the rise in triglycerides included baseline triglyceride levels, HCV genotype, and the type of interferon used. CONCLUSIONS: Serum triglyceride levels increase consistently in patients with chronic hepatitis C treated with all forms of a interferon, often to very high levels. These changes do not seem to be associated with clinical signs or complications and triglyceride levels decline while patients are still on therapy and return to normal after stopping.

Enantiomeric separation of metoprolol and alpha-hydroxymetoprolol by liquid chromatography and fluorescence detection using a chiral stationary phase.

A sensitive and stereoselective high-performance liquid chromatographic assay for the determination of the enantiomers of metoprolol (R- and S-) and the diastereoisomers of alpha-hydroxymetoprolol (IIA, IIB) in plasma is reported. Chromatography involved direct separation of enantiomers using a Chirobiotic T bonded phase column (250 x 4.6 mm) and a mobile phase consisting of acetonitrile-methanol-methylene chloride-glacial acetic acid-triethylamine (56:30:14:2:2, v/v). Solid-phase extraction using silica bonded with ethyl group (C2) was used to extract the compounds of interest from plasma and atenolol was used as the internal standard. The column effluent was monitored using fluorescence detection with excitation and emission wavelengths of 225 and 310 nm, respectively. S-Metoprolol, R-metoprolol, IIB and IIA eluted at about 5.9, 6.7, 7.3 and 8.2 min without any interfering peaks. The calibration curve was linear over the range of 0.5 to 100 ng/ml for each isomer of metoprolol and 1 to 100 ng/ml for each isomer of alpha-hydroxymetoprolol (IIA & IIB). The mean intra-run accuracies were in the range of 96.2 to 114% for R-metoprolol, 94.0 to 111% for S-metoprolol, 90.2 to 110% for IIA, and 94.6 to 106% for IIB. The mean intra-run precisions were all in the range of 2.2 to 12.0% for R-metoprolol, 2.1 to 11.1% for S-metoprolol, 1.9 to 14.5% for IIA, and 3.2 to 11.0% for IIB. The lowest level of quantitation for the enantiomers of metoprolol was 0.5 ng/ml and 1.0 ng/ml for alpha-hydroxymetoprolol (IIA and IIB). The absolute recoveries for each analyte was > or = 95%. The validated method accurately quantitated the enantiomers of parent drug and metabolite after a single dose of an extended release metoprolol formulation.

Small bowel perforation from a migrated biliary stent.

Stenting of the biliary tract is performed for a variety of benign and malignant disorders. Although uncommon, proximal and distal migration of these stents is known to occur. We report a case of jejunal perforation from a distally migrated biliary stent.

Combined cardio-renal transplantation (CCRT) from the same donor: report of two cases and review of the literature.

Two patients with successful combined cardio-renal transplantation (CCRT) using allografts from the same donor are reported. Both patients underwent staged procedure with hearts being transplanted first followed by kidneys. One patient suffered simultaneous acute rejection of both allografts, indeed a very rare event, which was successfully treated with pulse steroids. Because of the successful patient and graft outcomes, we propose that staged CCRT offers a reasonable therapeutic option for patients with co-existing, irreversible cardiorenal failure.

Spontaneous rupture of the liver upon revascularization during transplantation.

Spontaneous rupture of the liver has been described in association with many benign and malignant conditions. We report, to our knowledge, the first case of spontaneous rupture of the liver upon revascularization, requiring total hepatectomy and portocaval shunt, followed by successful retransplantation. Routine pathological examination of the explanted liver failed to reveal the etiology of the rupture. However, electron microscopy demonstrated abnormal collagen in the hepatic arterial wall compatible with a collagen disorder such as Ehlers-Danlos type IV disease. We conclude that the donor liver had a previously undiagnosed collagen disorder. Review of the literature does not preclude the use of livers from donors with a history of connective tissue disorders. Based on our experience one should exercise caution when using livers from such donors. With a history of connective tissue disorder in an immediate family member, further tests should be performed in the donor to rule out a subclinical connective tissue disorder. In addition, a review of all patients reported thus far to have undergone total hepatectomy and portocaval shunt, followed by liver transplantation as a two-stage procedure is presented.

Heterotopic pregnancy presenting as an acute abdomen: a diagnostic masquerader.

Simultaneous intrauterine and extrauterine pregnancy is called heterotopic pregnancy. It is a rare complication of pregnancy, especially in the absence of predisposing factors. It is known to present with a variety of symptoms and signs often leading to a delay in establishing the correct diagnosis. We report the case of a 29-year-old woman, known to be 14 weeks pregnant, presenting with acute abdominal pain. The confirmation of a viable intrauterine pregnancy led to a general surgery consultation. A heterotopic ruptured right ectopic tubal pregnancy was found. Right salpingectomy was performed. The patient recovered uneventfully. The intrauterine pregnancy was not affected. This case illustrates the variable presentation of heterotopic pregnancy and the need for general surgeons to be suspicious of pregnancy related complications, even in the presence of a viable intrauterine pregnancy.

Phenytoin pharmacokinetics following oral administration of phenytoin suspension and fosphenytoin solution to rats.

The administration of phenytoin suspension in conjunction with enteral nutrition supplements through nasogastric (NG) feeding tubes to humans has been associated with suboptimal phenytoin absorption, subtherapeutic concentrations, and breakthrough seizures. Postulated mechanisms include chelation to proteins and electrolytes in the enteral feeding, binding to NG tubing, and alterations in gastrointestinal pH resulting in precipitation of phenytoin. The purpose of this pilot study was to evaluate the oral absorption of commercially available fosphenytoin injectable solution compared to phenytoin suspension in the rat to determine whether equivalent oral fosphenytoin and phenytoin suspension doses should be used for future human studies of fosphenytoin oral absorption in the presence of concomitant enteral nutrition. A single oral 30 mg/kg phenytoin equivalents dose of either commercially available fosphenytoin or phenytoin suspension was administered to male Wistar rats following an overnight fast. Blood samples (0.3 ml) for phenytoin plasma concentration were obtained from a jugular vein catheter at baseline and 0.5, 1, 1.5, 2, 3, 4, 5, 8, 12 and 24 h post-study drug administration and analyzed by high performance liquid chromatography (HPLC) (CV% < 6). Mean phenytoin Cmax was 85% [corrected] (P = 0.010) higher in fosphenytoin vs phenytoin treated rats. Tmax was 2.4 h (62%, P=0.021) shorter in fosphenytoin vs phenytoin treated rats. No significant differences in AUClast were found. The presence of a phosphate ester moiety does not appear to inhibit the appearance of phenytoin following oral administration of fosphenytoin. Phenytoin plasma concentration profiles following oral administration of fosphenytoin are characterized by higher Cmax and shorter Tmax values relative to oral administration of phenytoin suspension.

Oxalate kinetics and reversal of the complications after orthotopic liver transplantation in a patient with primary hyperoxalosis type 1 awaiting renal transplantation.

We present the case of a young woman with end-stage renal disease secondary to primary hyperoxaluria type 1, who after 3 years and 6 months of maintenance hemodialysis, and despite intensification of the dialytic treatment, developed severe livedo reticularis in her extremities leading to ischemic cutaneous ulcerations, necessitating continuous intravenous infusion of narcotics for pain control. She received a liver transplant after native hepatectomy. However, due to positive crossmatch, she could not receive a kidney from that donor. After transplantation, following serial serum oxalate levels, the hemodialysis regimen was safely reduced from 4 h daily to 3 h three times weekly. Over the course of 6 weeks after liver transplantation, her livedo reticularis resolved, the ischemic ulcers markedly improved, she was weaned off all pain medications, and her erythropoietin-resistant anemia resolved. Our results suggest that in patients with primary hyperoxaluria type 1, who have received a liver transplant and are on maintenance hemodialysis, after serial serum oxalate determinations, some may safely be changed to a thrice-weekly maintenance hemodialysis regimen. Moreover, with this regimen the complications of systemic oxalosis can reverse.

Prognostic value of dipyridamole thallium-201 screening to minimize perioperative cardiac complications in diabetics undergoing kidney or kidney-pancreas transplantation.

To minimize perioperative cardiac events, we utilize a screening protocol consisting of intravenous dipyridamole thallium-201 myocardial imaging (DPT), with the selective use of coronary angiography based on the presence of reversible defect(s) on DPT test. A retrospective study was performed to determine the prognostic value of this protocol and to identify any clinical parameters predictive of an abnormal DPT test. To accomplish this, a detailed chart analysis of 176 consecutive kidney (n = 89) and kidney-pancreas (n = 87) transplant recipients who had undergone pretransplant DPT testing was performed. The results of the DPT test were interpreted as normal in 111, fixed defect in 15, and reversible defect(s) in 50 patients. Forty-two of the 50 patients with reversible defect(s) underwent coronary angiography. Twelve of the 27 patients with significant coronary artery disease (CAD, > 50% stenosis in one or more coronary arteries) underwent pretransplant revascularization and the remaining 15 were treated medically. Cardiac events (documented acute myocardial infarction or sudden cardiac death) within 6 wk of transplant were stratified by the results of this protocol. Also, various clinical parameters were compared between patients with normal and abnormal (fixed and reversible defect) DPT tests. Only one of the 111 (0.9%) transplant recipients with a normal DPT test had a perioperative cardiac event. None of the 15 (0%) patients with a fixed defect and none of the 15 (0%) patients with reversible defect(s), but a nonsignificant (< 50% narrowing) coronary angiogram, had a perioperative cardiac event. Three of the 27 (11.1%) patients with reversible defect(s) and significant disease on coronary angiography, who had undergone pre-transplant revascularization or were managed medically, had a perioperative coronary event. Of 14 recipients parameters analyzed, age > 50 yr was the only variable predictive of an abnormal DPT test. We conclude that the incidence of perioperative cardiac events in patients with a normal or fixed defect, or reversible defect(s) but a nonsignificant (< 50% narrowing) coronary angiogram is very low, indicating the high correlation of these findings on DPT and an uneventful (cardiac) post-transplant course. The incidence of perioperative cardiac complications amongst the high-risk transplant recipients with reversible defect(s) and significant CAD on coronary angiogram may be minimized by appropriate preoperative medical management or revascularization. None of the clinical variables except age > 50 yr was predictive of an abnormal DPT test.

A sensitive assay of metoprolol and its major metabolite alpha-hydroxy metoprolol in human plasma and determination of dextromethorphan and its metabolite dextrorphan in urine with high performance liquid chromatography and fluorometric detection.

A reverse-phase High Performance Liquid Chromatographic (HPLC) method was developed for the analysis of metoprolol in the large number of human plasma samples obtained in in vitro-in vivo correlations (IVIVC) and bioavailability studies of extended release formulations of metoprolol tartrate. The metabolite, alpha-hydroxy metoprolol (OH-met), could also be quantified. The analytes were extracted from the plasma using solid phase columns, separated on a C-4 analytical column followed by fluorimetric detection. The linearity, precision, accuracy, stability, selectivity and ruggedness were validated for the concentration ranges of 1-400 ng ml-1 for metoprolol and 0.5-200 ng ml-1 for OH-met. The same chromatographic conditions were slightly modified to quantify dextromethorphan and its metabolite dextrorphan in urine in the concentration range 0.052-0.05 microgram ml-1 as a method for screening for fast metabolizers.

Renoprotective effects of the 21-aminosteroid U74389G in ischemia-reperfusion injury and cold storage preservation.

Free radical mediated lipid peroxidation (LPO) has been implicated in the pathogenesis of ischemic-reperfusion injury (IRI). To address the renoprotective effect(s) of LPO inhibition, the efficacy of the 21 aminosteroid U74389G was evaluated in three IRI models. In Model 1 51 unilateral nephrectomized rats that underwent 60 min of warm ischemia followed by a 72-hr reperfusion interval were treated with the test vehicle only, or 3, 6, or 12 mg/kg of U74389G intravenously, 5 min pre- or postischemia. In Model 2 Sprague-Dawley rats underwent sham operation (n=9), or 45 min of warm ischemia and 10 min of reperfusion with U74389G (6 mg/kg; n=10) or test vehicle only (n=10) administered intravenously over 10 min beginning 5 min prior to clamp release. After reperfusion, LPO was determined by assay of snap frozen tissue for thiobarbituric acid (TBA) concentrations (nmol/g tissue weight). In Model 3 domestic lean maid pigs (14-18 kg) underwent left nephrectomy with 30 min of warm ischemia, Collins C-4 flush, and 24 hr of cold storage preservation. Heterotopic autotransplantation and immediate contralateral nephrectomy was then performed in Group A-nonischemic controls (n=4), Group B-ischemic controls (n=5), and Group C-U74389G (6 mg/kg) administered preischemia and at autotransplantation (n=5). In Model 1 maximal renoprotection was demonstrated with the 6 mg/kg dose of U74389G administered after ischemia (ischemic control 72-hr serum creatinine (Cr) = 8.01+/-1.1 mg% vs. 3.32+/-0.96 mg%; ischemic control creatinine clearance = 0.069+/-0.03 ml/min vs. 0.206+/-0.04 ml/min; P<0.05). In Model 2 TBA levels were significantly lower in U74389G treated animals (88.5+/-10.0 vs. ischemic controls = 296.8+/-81.4; P=0.02). In Model 3 graft survivals were 100%, 0%, and 60% respectively. Peak Cr and BUN (mg%) were significantly greater in Group C vs. Group A, (Group A Cr = 8.59+/-0.63 vs. Group C = 12.8+/-1.01; Group A BUN = 64.1+/-2.73 vs. Group C = 104.9+/-12.21)--however, by day 10, thee were no significant differences in renal function: (Group A Cr = 2.15+/-0.3 vs. Group C = 2.10+/-0.06; Group A BUN = 27.0+/-6.0 vs. Group C = 31.1+/-6.4). These results support the beneficial effects of LPO inhibitors in models of ischemia-reperfusion, as well as preservation/transplantation, and suggest that this renoprotection correlates with decreased membrane lipid peroxidation.

Outcome and utility of scoring systems in the management of the mangled extremity.

BACKGROUND: The role of scoring systems as predictors of amputation and functional outcome in severe blunt extremity trauma was examined. METHODS: All severe extremity injuries treated over a 10-year period were scored retrospectively using four scoring systems: Mangled Extremity Syndrome Index (MESI), Mangled Extremity Severity Score (MESS), Predictive Salvage Index (PSI), and Limb Salvage Index (LSI). RESULTS: Twenty-three upper (UE) and 51 lower extremity (LE) injuries were evaluated. Sensitivity and specificity, respectively, were MESI 100% and 50%, MESS 79% and 83%, PSI 96% and 50%, and LSI 83% and 83%. For each system, there were no differences between patients with good and poor functional outcomes. CONCLUSION: All of the scoring systems were able to identify the majority of patients who required amputation. However, prediction in individual patients was problematic. None of the scoring systems were able to predict functional outcome.