Cost-effectiveness Analysis for Technology Acquisition

Background

In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.

Methods

The present study analysed cost-effectiveness of an “In-house” magnetic resonance imaging (MRI) scan facility of a large service hospital against outsourcing possibilities. Cost per unit scan was calculated by operating costing method and break-even volume was calculated. Then life-cycle cost analysis was performed to enable total cost visibility of the MRI scan in both “In-house” and “outsourcing of facility” configuration. Finally, cost-effectiveness analysis was performed to identify the more acceptable decision option.

Result

Total cost for performing unit MRI scan was found to be Rs 3,875 for scans without contrast and Rs 4,129 with contrast. On life-cycle cost analysis, net present value (NPV) of the “In-house” configuration was found to be Rs-(4,09,06,265) while that of “outsourcing of facility” configuration was Rs-(5,70,23,315). Subsequently, cost-effectiveness analysis across eight Figures of Merit showed the “In-house” facility to be the more acceptable option for the system.

Conclusion

Every decision for acquiring high-end technology must be subjected to life-cycle cost analysis.Key Words: Technology assessment, Cost benefit analysis, Cost-effectiveness analysis     

Cost-effectiveness analysis for technology acquisition

Background: In a developing country with limited resources, it is important to utilize the total cost visibility approach over the entire life-cycle of the technology and then analyse alternative options for acquiring technology.     

A 3-year prospective study of Post-traumatic Stress Disorder in Israeli combat veterans

This study attempted to trace the long-term psychiatric sequelae of combat in a large representative sample of combat stress reaction (CSR) Israeli casualties and matched controls. Employing DSM-III criteria for Post-traumatic Stress Disorder (PTSD) subjects were assessed 1, 2, and 3 years after their participation in the war. Results show that CSR casualties had dramatically higher rates of PTSD than controls at all three points of time. In both groups a decline in prevalence and breadth of PTSD was observed over time. The passage of time had a differential effect on the symptom profile of the CSR casualties and controls. Theoretical, methodological, and treatment implications are discussed.     

Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma

AIM: To develop and assess a protocol for the treatment of intraocular lymphoma by intravitreal injection of methotrexate and thiotepa. METHODS: A patient with intraocular non-Hodgkin's lymphoma which recurred after radiotherapy and repeated systemic chemotherapeutic regimens underwent repeated intravitreal injections of methotrexate and thiotepa. The patient was closely monitored by cytology, anterior chamber flare measurements, IL-10 and IL-6 levels. Methotrexate drug clearance studies were performed on vitreous samples taken before each injection. RESULTS: Complete tumour clearance was achieved by the third week of therapy. IL-10 and IL-6 levels quickly dropped to barely detectable levels as the tumour was cleared from the eye. Flare measurements decreased from 500 to 15 photons/s over the same time. A plot of the methotrexate levels over time revealed a first order kinetic rate of elimination with an effective tumoricidal intravitreal dose persisting for 5 days after injection. CONCLUSION: Intravitreal chemotherapy for the treatment of recurrent intraocular lymphoma appears effective in prolonging local remission of ocular disease even in the presence of an aggressively growing tumour. A single intravitreal injection of methotrexate can lead to a prolonged tumoricidal concentration lasting for a longer period than that achieved by systemic administration.     

Giant congenital neuroid melanocytic nevus

A patient with a variety of nevus cell nevi, a congenital giant melanocytic nevus, abnormal facies, vascular anomaly of the leg, and mental retardation was examined. The patient also had neuroid elements within the giant nevus that led to the consideration of neurofibromatosis. Because neurofibromatosis is a genetically determined condition with tissue different from the neuroid elements seen in giant nevi, the two conditions are considered to be different entities. Malignant transformation of congenital giant pigmented nevi occurs, although the incidence of such transformation remains a subject of controversy.     

Inositol hexakisphosphate kinase-2 determines cellular energy dynamics by regulating creatine kinase-B

Inositol hexakisphosphate kinases (IP6Ks) regulate various biological processes. IP6Ks convert IP6 to pyrophosphates such as diphosphoinositol pentakisphosphate (IP7) and bis-diphosphoinositol tetrakisphosphate (IP8). IP7 is produced in mammals by a family of inositol hexakisphosphate kinases, IP6K1, IP6K2, and IP6K3, which have distinct biological functions. The inositol hexakisphosphate kinase 2 (IP6K2) controls cellular apoptosis. To explore roles for IP6K2 in brain function, we elucidated its protein interactome in mouse brain revealing a robust association of IP6K2 with creatine kinase-B (CK-B), a key enzyme in energy homeostasis. Cerebella of IP6K2-deleted mice (IP6K2-knockout [KO]) produced less phosphocreatine and ATP and generated higher levels of reactive oxygen species and protein oxidative damage. In IP6K2-KO mice, mitochondrial dysfunction was associated with impaired expression of the cytochrome-c1 subunit of complex III of the electron transport chain. We reversed some of these effects by combined treatment with N-acetylcysteine and phosphocreatine. These findings establish a role for IP6K2–CK-B interaction in energy homeostasis associated with neuroprotection.

Inositol pyrophosphates are versatile messenger molecules that mediate a variety of cellular functions, including cell growth, apoptosis, endocytosis, and cell differentiation. The most extensively studied inositol pyrophosphate, diphosphoinositol pentakisphosphate (IP7), displays a 5′-diphosphate (1, 2). IP7 is generated in mammals by a family of inositol hexakisphosphate kinases (IP6Ks) (3, 4). IP6Ks exists in three isoforms: IP6K1, IP6K2, and IP6K3. Inositol hexakisphosphate kinase-2 (IP6K2) sensitizes cells to apoptosis (5, 6). Mice with targeted deletion of IP6K2 display an increased incidence of aero-digestive tract carcinoma (7). Cell survival associated with heat shock protein 90 also involves IP6K2 (8, 9).We previously reported a major role for IP6K2 in the disposition of cerebellar granule cells as well as Purkinje cell morphology and motor coordination. The influence of IP6K2 upon cerebellar disposition involved protein 4.1N, both of which were highly expressed in cerebellar granule cells (10).To further assess the functions of IP6K2 in the brain, we explored its binding partners using coimmunoprecipitation and tandem liquid chromatography mass spectrometry (LC-MS/MS). Here, we report that IP6K2 robustly interacts with creatine kinase-B (CK-B), which regulates energy homeostasis of cells and exists in two forms, brain type (CK-B) and muscle type (CK-M). CK catalyzes the reversible transfer of the phosphate group of phosphocreatine to ADP to yield ATP (11, 12). A functional interplay between mitochondrial and cytosolic isoforms of CK regulates cellular energy homeostasis. Cytosolic CK rephosphorylates locally produced free ADP and increases creatine globally, while the mitochondrial enzyme catalyzes the conversion of creatine to phosphocreatine utilizing mitochondrial ATP (13–15).Here, we show that IP6K2 loss leads to decreased CK-B expression, reduced ATP levels, and diminished mitochondrial activity associated with increased oxidative stress. About 80 to 90% of ATP is generated in the mitochondria by oxidative phosphorylation, and diminished ATP levels are the immediate effect of mitochondrial dysfunction. Loss of IP6K2 and CK-B reflects the suppression of the mitochondrial cytochrome c1 expression, a component of complex III of the mitochondrial electron transport chain. In the present study, we report a physiologic association of CK-B and IP6K2, whose disruption impacts mitochondrial functions.Dendritic morphogenesis was reduced in IP6K2-deficient neurons and was rescued by restoring normal levels of ATP. These observations reveal an essential role of IP6K2 in the energy production of the brain. Our findings indicate that IP6K2 is a key regulator of mitochondrial homeostasis which promotes neuroprotection.     

Catheter ablation of hemodynamically compromising incessant atrioventricular tachycardia.

A 27-year-old woman was admitted to the Georgetown University Hospital with refractory hemodynamically compromising incessant atrioventricular tachycardia. A single left-sided accessory pathway was identified and successfully modified acutely. Endocardial delivery of direct current energy provided an extremely effective therapeutic intervention resulting in termination of atrioventricular tachycardia and restoration of stable hemodynamic status. Although a second ablation procedure was necessary to permanently interrupt accessory pathway conduction, the patient has remained free of symptoms without medications for 13 months.     

Nutritional status and serum cytokine profiles in children, adolescents, and young adults with Schistosoma japonicum-associated hepatic fibrosis, in Leyte, Philippines

In a cross-sectional study of 641 Schistosoma japonicum-infected individuals in Leyte, Philippines, who were 7-30 years old, we determined the grade of hepatic fibrosis (HF) by ultrasound and used anthropometric measurements and hemoglobin levels to assess nutritional status. Serum levels of interleukin (IL)-1, IL-6, and IL-10; tumor-necrosis factor (TNF)-alpha; soluble TNF- alpha receptor I; and C-reactive protein (CRP) were measured to examine the association between these markers of inflammation and HF grade. HF was present in 8.9% of the cohort; the majority of cases were mild (grade I), and severe (grade II or grade III) cases occurred only in male individuals. Compared with individuals without HF, those with severe HF--and, to a lesser degree, those with mild HF--had a significantly lower body-mass index (BMI) and BMI z-score, a higher prevalence of anemia, and a higher level of CRP and were more likely to produce IL-6; furthermore, those with severe HF had a significantly higher level of IL-1, compared with those either without HF or with mild HF. These findings suggest that even mild HF is associated with nutritional morbidity and underscore the importance of early recognition and treatment. In addition, our data are consistent with the hypothesis that, by systemically increasing the levels of the proinflammatory cytokines IL-1 and IL-6, HF causes undernutrition and anemia.     

Evaluation and characterization of tumor lysis syndrome before and after chemotherapy among pediatric oncology patients in Tikur Anbessa specialized hospital,Addis Ababa,Ethiopia

Background

Tumor lysis syndrome (TLS) is a life-threatening emergency disorder, caused by an abrupt release of intracellular metabolites after tumor cell death. It is characterized by a series of metabolic manifestations, especially hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. The aim of this study was to evaluate and characterize the incidence of tumor lysis syndrome among pediatric oncology patients before and after treatment.

Methods

Hospital based prospective cohort study was conducted for 6 months on 61 newly diagnosed pediatric oncology patients. Socio-demographic data was collected by interview administered questionnaire. Patients were followed and the physical diagnosis, imaging and laboratory results were interpreted by senior physicians. Data was entered to and analyzed by SPSS version 23.

Results

Among 61 pediatric oncology patients 39(63.9%) were males. The mean (±SD) age of the pediatric patients was 6.39 (±?3.67) years ranging from 2 months to 14 years. 29.5% of patients were found to have TLS. There were 11.5% and 18.0% of laboratory TLS (LTLS) and clinical TLS (CTLS) cases respectively. There were72.2% spontaneous and 27.8% treatment induced TLS cases with 23% and 21.3% cases of hyperuricemia and 4.9% and 6.6% cases of hyperkalemia incidence before and after treatment respectively. Only two patients died, in the study period, due to TLS.

Conclusion

There was high incidence of TLS irrespective of socio-demographic variation among study participants, suggesting that children with cancer are at risk of developing TLS. As TLS is a life-threatening complication of malignancies, early identification of patients at risk and reducing morbidity and mortality is crucially important.